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Lorenzo IUGHETTI

Professore Ordinario
Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto


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Pubblicazioni

2024 - Bi-allelic genetic variants in the translational GTPases GTPBP1 and GTPBP2 cause a distinct identical neurodevelopmental syndrome [Articolo su rivista]
Salpietro, V.; Maroofian, R.; Zaki, M. S.; Wangen, J.; Ciolfi, A.; Barresi, S.; Efthymiou, S.; Lamaze, A.; Aughey, G. N.; Al Mutairi, F.; Rad, A.; Rocca, C.; Cali, E.; Accogli, A.; Zara, F.; Striano, P.; Mojarrad, M.; Tariq, H.; Giacopuzzi, E.; Taylor, J. C.; Oprea, G.; Skrahina, V.; Rehman, K. U.; Abd Elmaksoud, M.; Bassiony, M.; El Said, H. G.; Abdel-Hamid, M. S.; Al Shalan, M.; Seo, G.; Kim, S.; Lee, H.; Khang, R.; Issa, M. Y.; Elbendary, H. M.; Rafat, K.; Marinakis, N. M.; Traeger-Synodinos, J.; Ververi, A.; Sourmpi, M.; Eslahi, A.; Khadivi Zand, F.; Beiraghi Toosi, M.; Babaei, M.; Jackson, A.; Hannah, M. G.; Bugiardini, E.; Bertini, E.; Kriouile, Y.; El-Khorassani, M.; Aguennouz, M.; Groppa, S.; Karashova, B. M.; Goraya, J. S.; Sultan, T.; Avdjieva, D.; Kathom, H.; Tincheva, R.; Banu, S.; Veggiotti, P.; Verrotti, A.; Lanari, M.; Savasta, S.; Macaya, A.; Garavaglia, B.; Borgione, E.; Papacostas, S.; Vikelis, M.; Chelban, V.; Kaiyrzhanov, R.; Cortese, A.; Sullivan, R.; Papanicolaou, E. Z.; Dardiotis, E.; Maqbool, S.; Ibrahim, S.; Kirmani, S.; Rana, N. N.; Atawneh, O.; Lim, S. -Y.; Zuccotti, G. V.; Marseglia, G. L.; Esposito, S.; Shaikh, F.; Cogo, P.; Corsello, G.; Mangano, S.; Nardello, R.; Mangano, D.; Scardamaglia, A.; Koutsis, G.; Scuderi, C.; Ferrara, P.; Morello, G.; Zollo, M.; Berni-Canani, R.; Terracciano, L. M.; Sisto, A.; Di Fabio, S.; Strano, F.; Scorrano, G.; Di Bella, S.; Di Francesco, L.; Manizha, G.; Isrofilov, M.; Guliyeva, U.; Salayev, K.; Khachatryan, S.; Xiromerisiou, G.; Spanaki, C.; Fiorillo, C.; Iacomino, M.; Gaudio, E.; Munell, F.; Gagliano, A.; Jan, F.; Chimenz, R.; Gitto, E.; Iughetti, L.; Di Rosa, G.; Maghnie, M.; Pettoello-Mantovani, M.; Gupta, N.; Kabra, M.; Benrhouma, H.; Tazir, M.; Bottone, G.; Farello, G.; Delvecchio, M.; Di-Donato, G.; Obeid, M.; Bakhtadze, S.; Saadi, N. W.; Miraglia-Del-Giudice, M.; Maccarone, R.; Triki, C. C.; Kara, M.; Karimiani, E. G.; Salih, A. M.; Ramenghi, L. A.; Seri, M.; Di-Falco, G.; Mandara, L.; Barrano, G.; Elisa, M.; Cherubini, E.; Operto, F. F.; Valenzise, M.; Cattaneo, A.; Zazzeroni, F.; Alesse, E.; Matricardi, S.; Zafar, F.; Ullah, E.; Afzal, E.; Rahman, F.; Ahmed, M. M.; Parisi, P.; Spalice, A.; De Filippo, M.; Licari, A.; Trebbi, E.; Romano, F.; Heimer, G.; Al-Khawaja, I.; Al-Mutairi, F.; Alkuraya, F. S.; Rizig, M.; Shashkin, C.; Zharkynbekova, N.; Koneyev, K.; Bertoli-Avella, A.; Pagnamenta, A. T.; Niceta, M.; Battini, R.; Corsello, A.; Leoni, C.; Chiarelli, F.; Dallapiccola, B.; Faqeih, E. A.; Tallur, K. K.; Alfadhel, M.; Alobeid, E.; Maddirevula, S.; Mankad, K.; Banka, S.; Ghayoor-Karimiani, E.; Tartaglia, M.; Chung, W. K.; Green, R.; Jepson, J. E. C.; Houlden, H.
abstract

The homologous genes GTPBP1 and GTPBP2 encode GTP-binding proteins 1 and 2, which are involved in ribosomal homeostasis. Pathogenic variants in GTPBP2 were recently shown to be an ultra-rare cause of neurodegenerative or neurodevelopmental disorders (NDDs). Until now, no human phenotype has been linked to GTPBP1. Here, we describe individuals carrying bi-allelic GTPBP1 variants that display an identical phenotype with GTPBP2 and characterize the overall spectrum of GTP-binding protein (1/2)-related disorders. In this study, 20 individuals from 16 families with distinct NDDs and syndromic facial features were investigated by whole-exome (WES) or whole-genome (WGS) sequencing. To assess the functional impact of the identified genetic variants, semi-quantitative PCR, western blot, and ribosome profiling assays were performed in fibroblasts from affected individuals. We also investigated the effect of reducing expression of CG2017, an ortholog of human GTPBP1/2, in the fruit fly Drosophila melanogaster. Individuals with bi-allelic GTPBP1 or GTPBP2 variants presented with microcephaly, profound neurodevelopmental impairment, pathognomonic craniofacial features, and ectodermal defects. Abnormal vision and/or hearing, progressive spasticity, choreoathetoid movements, refractory epilepsy, and brain atrophy were part of the core phenotype of this syndrome. Cell line studies identified a loss-of-function (LoF) impact of the disease-associated variants but no significant abnormalities on ribosome profiling. Reduced expression of CG2017 isoforms was associated with locomotor impairment in Drosophila. In conclusion, bi-allelic GTPBP1 and GTPBP2 LoF variants cause an identical, distinct neurodevelopmental syndrome. Mutant CG2017 knockout flies display motor impairment, highlighting the conserved role for GTP-binding proteins in CNS development across species.


2024 - Endocrine features of Prader-Willi syndrome: a narrative review focusing on genotype-phenotype correlation [Articolo su rivista]
Madeo, S. F.; Zagaroli, L.; Vandelli, S.; Calcaterra, V.; Crino, A.; De Sanctis, L.; Faienza, M. F.; Fintini, D.; Guazzarotti, L.; Licenziati, M. R.; Mozzillo, E.; Pajno, R.; Scarano, E.; Street, M. E.; Wasniewska, M.; Bocchini, S.; Bucolo, C.; Buganza, R.; Chiarito, M.; Corica, D.; Di Candia, F.; Francavilla, R.; Fratangeli, N.; Improda, N.; Morabito, L. A.; Mozzato, C.; Rossi, V.; Schiavariello, C.; Farello, G.; Iughetti, L.; Salpietro, V.; Salvatoni, A.; Giordano, M.; Grugni, G.; Delvecchio, M.
abstract

Prader-Willi syndrome (PWS) is a complex genetic disorder caused by three different types of molecular genetic abnormalities. The most common defect is a deletion on the paternal 15q11-q13 chromosome, which is seen in about 60% of individuals. The next most common abnormality is maternal disomy 15, found in around 35% of cases, and a defect in the imprinting center that controls the activity of certain genes on chromosome 15, seen in 1-3% of cases. Individuals with PWS typically experience issues with the hypothalamic-pituitary axis, leading to excessive hunger (hyperphagia), severe obesity, various endocrine disorders, and intellectual disability. Differences in physical and behavioral characteristics between patients with PWS due to deletion versus those with maternal disomy are discussed in literature. Patients with maternal disomy tend to have more frequent neurodevelopmental problems, such as autistic traits and behavioral issues, and generally have higher IQ levels compared to those with deletion of the critical PWS region. This has led us to review the pertinent literature to investigate the possibility of establishing connections between the genetic abnormalities and the endocrine disorders experienced by PWS patients, in order to develop more targeted diagnostic and treatment protocols. In this review, we will review the current state of clinical studies focusing on endocrine disorders in individuals with PWS patients, with a specific focus on the various genetic causes. We will look at topics such as neonatal anthropometry, thyroid issues, adrenal problems, hypogonadism, bone metabolism abnormalities, metabolic syndrome resulting from severe obesity caused by hyperphagia, deficiencies in the GH/IGF-1 axis, and the corresponding responses to treatment.


2024 - Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study [Articolo su rivista]
Dharmayat, K. I.; Vallejo-Vaz, A. J.; Stevens, C. A. T.; Brandts, J. M.; Lyons, A. R. M.; Groselj, U.; Abifadel, M.; Aguilar-Salinas, C. A.; Alhabib, K.; Alkhnifsawi, M.; Almahmeed, W.; Alnouri, F.; Alonso, R.; Al-Rasadi, K.; Ashavaid, T. F.; Banach, M.; Béliard, S.; Binder, C.; Bourbon, M.; Chlebus, K.; Corral, P.; Cruz, D.; Descamps, O. S.; Drogari, E.; Durst, R.; Ezhov, M. V.; Genest, J.; Harada-Shiba, M.; Holven, K. B.; Humphries, S. E.; Khovidhunkit, W.; Lalic, K.; Laufs, U.; Liberopoulos, E.; Roeters van Lennep, J.; Lima-Martinez, M. M.; Lin, J.; Maher, V.; März, W.; Miserez, A. R.; Mitchenko, O.; Nawawi, H.; Panayiotou, A. G.; Paragh, G.; Postadzhiyan, A.; Reda, A.; Reiner, Ž.; Reyes, X.; Sadiq, F.; Sahebkar, A.; Schunkert, H.; Shek, A. B.; Stroes, E.; Su, T. C.; Subramaniam, T.; Susekov, A.; Vázquez Cárdenas, A.; Huong Truong, T.; Tselepis, A. D.; Vohnout, B.; Wang, L.; Yamashita, S.; Al-Sarraf, A.; Al-Sayed, N.; Davletov, K.; Dwiputra, B.; Gaita, D.; Kayikcioglu, M.; Latkovskis, G.; Marais, A. D.; Thushara Matthias, A.; Mirrakhimov, E.; Nordestgaard, B. G.; Petrulioniene, Z.; Pojskic, B.; Sadoh, W.; Tilney, M.; Tomlinson, B.; Tybjærg-Hansen, A.; Viigimaa, M.; Catapano, A. L.; Freiberger, T.; Hovingh, G. K.; Mata, P.; Soran, H.; Raal, F.; Watts, G. F.; Schreier, L.; Bañares, V.; Greber-Platzer, S.; Baumgartner-Kaut, M.; de Gier, C.; Dieplinger, H.; Höllerl, F.; Innerhofer, R.; Karall, D.; Lischka, J.; Ludvik, B.; Mäser, M.; Iughetti, L.; Scholl-Bürgi, S.
abstract

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 21% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 130 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (188%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (502%) of 11 476 included individuals were female and 5720 (498%) were male. Sex data were missing for 372 (31%) of 11 848 individuals. Median age at registry entry was 96 years (IQR 58-132). 10 099 (899%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (101%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (52%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [924%] of 10 202) than in children and adolescents from non-high-income countries (199 [480%] of 415). 3414 (316%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (724%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 500 mmol/L (IQR 405-608). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation.Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life.


2024 - Fentanyl analgesia in asphyxiated newborns treated with therapeutic hypothermia [Articolo su rivista]
Lugli, L.; Spada, C.; Garetti, E.; Guidotti, I.; Roversi, M. F.; Della Casa, E.; Bedetti, L.; Lucaccioni, L.; Pugliese, M.; Ferrari, F.; Iughetti, L.; Lago, P.; Berardi, A.
abstract

Introduction: Therapeutic hypothermia is the standard care for asphyxiated newborns. Discomfort and pain during treatment are common and may affect therapeutic efficacy of hypothermia. Opioid analgosedation is commonly used in the clinical setting, but its effects in the cooled newborns is poorly investigated. Objective: The aim of this study was to assess the safety of fentanyl analgosedation during therapeutic hypothermia, by evaluating severe adverse effects and possible correlation with the neurodevelopmental outcome. Methods: We analyzed asphyxiated newborns treated with hypothermia receiving fentanyl intravenous infusion (years 2013–2018). Severe neurodevelopmental outcome was defined as cerebral palsy or Griffith’s developmental quotient <70 or major sensorineural deficit. Severe brain lesions were defined as cortical or/and basal ganglia extensive involvement. Results: Fentanyl cumulative dose was variable (61.7 ± 18.5 µg/kg; range 34.3–120.3 µg/kg) among 45 enrolled patients. Respiratory depression was recorded in 13.3% cases of 30 spontaneously breathing patients. Severe brain lesions and severe neurodevelopmental disability were found in 24.4 and 11.1% of all included cases, respectively. Higher cumulative fentanyl dose was not associated with poor outcome. Conclusions: Fentanyl treatment during therapeutic hypothermia does not negatively affect the neurodevelopmental outcome, thus on the contrary, it may contribute to ameliorate neuroprotection in the asphyxiated cooled newborns.


2024 - Fetal hepatic calcification in severe KAT6A (Arboleda-Tham) syndrome [Articolo su rivista]
Di Caprio, A.; Rossi, C.; Bertucci, E.; Bedetti, L.; Bertoncelli, N.; Miselli, F.; Corso, L.; Bondi, C.; Iughetti, L.; Berardi, A.; Lugli, L.
abstract

: Arboleda-Tham syndrome (ARTHS, MIM 616268) is a rare genetic disease, due to a pathogenic variant of Lysine (K) Acetyltransferase 6A (KAT6A) with autosomal dominant inheritance. Firstly described in 2015, ARTHS is one of the more common causes of undiagnosed syndromic intellectual disability. Due to extreme phenotypic variability, ARTHS clinical diagnosis is challenging, mostly at early stage of the disease. Moreover, because of the wide and unspecific spectrum of ARTHS, identification of the syndrome during prenatal life rarely occurs. Therefore, reported cases of KAT6A syndrome have been identified primarily through clinical or research exome sequencing in a gene-centric approach. In order to expands the genotypic and phenotypic spectrum of ARTHS, we describe prenatal and postnatal findings in a patient with a novel frameshift KAT6A pathogenic variant, displaying a severe phenotype with previously unreported clinical features.


2024 - Investigating Eating Habits of Children Aged between 6 Months and 3 Years in the Provinces of Modena and Reggio Emilia: Is Our Kids’ Diet Sustainable for Their and the Planet’s Health? [Articolo su rivista]
Palandri, L; Rocca, L; Scasserra, Mr; Vigezzi, Pg; Iughetti, L; Lucaccioni, L; Righi, E
abstract

A healthy and balanced diet is crucial for children’s well-being and aids in preventing diet-related illnesses. Furthermore, unhealthy dietary habits indirectly impact children’s health, as the food industry stands as one of the primary drivers of climate change. Evidence shows the Mediterranean diet is sustainable for both children’s and the planet’s health. The aim of this crosssectional study was to evaluate the eating habits of children aged between 6 months and 3 years, in the province of Modena and Reggio Emilia, in Italy, along with their adherence to the guidelines for a healthy diet, and examine the role of pediatricians in promoting knowledge about nutrition and sustainability. In our sample (218 children), most children exceeded the recommended meat and cheese intake, while consuming insufficient amounts of vegetables, fruit, and legumes. Vegetable and fruit consumption declined with the increase in age category while eating sweets, soft drinks, and processed food increased. Incorporating school meals’ data into this analysis, we observed a modification in dietary compliance, characterized by an increase in meat and cheese consumption, alongside improvements in the intake of vegetables, fruits, fish, eggs, and legumes. This study suggests that supporting an integrated approach that combines social and educational initiatives is crucial. Future research should prioritize fostering sustainable eating habits within communities to facilitate dietary habits’ transformation and encourage healthier lifestyles.


2024 - Minipuberty in Male Full-term Neonates Appropriate and Small for Gestational Age and in Preterm Babies: Data from a Single Centre [Articolo su rivista]
Boncompagni, A.; Pietrella, E.; Passini, E.; Grisolia, C.; Tagliazucchi, M.; Tagliafico, E.; Lugli, L.; Berardi, A.; Iughetti, L.; Lucaccioni, L.
abstract

Objective: The postnatal activation of the hypothalamic-pituitary-gonadal (HPG) axis is usually known as “minipuberty”. There are still open questions about its biological function and significance depending on sex, gestational age (GA) and birth weight (BW) with few available longitudinal data. Methods: A single-centre, longitudinal study to quantify urinary follicle stimulating hormone (uFSH), luteinizing hormone (uLH) and testosterone (uTs) in male neonates. Neonates were enrolled and stratified into three subgroups: full-term boys appropriate for GA (FT AGA); FT boys with BW ≤3rd centile [FT small for gestational age (SGA)]; and preterm (PT) boys ≤33 weeks of GA. Urinary hormones were correlated to simultaneous auxological parameters, linear growth and external genitalia at scheduled time-points. Results: Forty-six boys were recruited, with subgroup sizes FT AGA n=23, FT SGA n=11 and PT n=12. PT boys display a pulsatile pattern of urinary gonadotropins (uGns) with higher levels of uLH and a gradual increase of uTs. Testicular descent started from 29-32 weeks with the peak of uTs. During the first 12-months post-term age (PTA), FT AGA boys displayed a better linear growth (p<0.05). PT showed higher uGns levels until 3-months PTA. PT babies had higher uLH levels than FT AGA, with a peak at 7 and 30 days, during the first 90 days of life (p<0.001) and higher uTs levels. Correlation analysis between penile growth of all neonates and uTs was significant (p=0.04) but not within subgroups. Conclusion: This study investigated postnatal HPG axis activation in term and PT infants. Minipuberty may involve an early window of opportunity to evaluate the functionality of the HPG axis. Further studies with a long-term follow-up are needed with a special focus on possible consequences of GA and BW.


2024 - Nasal glucagon is safe and effective in children and adolescents with type 1 diabetes: A real-world prospective cohort study [Articolo su rivista]
Zucchini, S.; Ripoli, C.; Cherubini, V.; Coccioli, M. S.; Delvecchio, M.; De Marco, R.; Franceschi, R.; Gallo, F.; Graziani, V.; Iafusco, D.; Innaurato, S.; Lasagni, A.; Lombardo, F.; Marigliano, M.; Monti, S.; Pascarella, F.; Pezzino, G.; Predieri, B.; Rabbone, I.; Schiaffini, R.; Trada, M.; Tumini, S.; Scaramuzza, A.; the Baqsimi Study Group, Collaborators; Maltoni, G; Bernardini, L; Tiberi, V; Suprani, T; Passanisi, S; Tomaselli, L; Iughetti, L; Tinti, D; Ricciardi, R.
abstract


2024 - Neurodevelopmental outcome of neonatal seizures: A longitudinal study [Articolo su rivista]
Lugli, L.; Bariola, M. C.; Guidotti, I.; Pugliese, M.; Roversi, M. F.; Bedetti, L.; Della Casa Muttini, E.; Miselli, F.; Ori, L.; Lucaccioni, L.; Bertoncelli, N.; Rossi, K.; Crestani, S.; Bergonzini, P.; Iughetti, L.; Ferrari, F.; Berardi, A.
abstract

Introduction: Neonatal seizures (NS) are the most common neurological emergency in the neonatal period. The International League Against Epilepsy (ILAE) proposed a new classification of NS based on semiology and highlighted the correlation between semiology and aetiology. However, neurodevelopmental outcomes have not been comprehensively evaluated based on this new classification. Aims: To evaluate neurodevelopmental outcomes and potential risk factors for severe outcomes in NS. Methods: Patients with video electroencephalogram confirmed NS were evaluated. Seizure aetiology, cerebral magnetic resonance imaging (MRI) data, background electroencephalograms data, general movements, and neurodevelopmental outcomes were analysed. Severe outcomes were one of the following: death, cerebral palsy, Griffiths developmental quotient <70, epilepsy, deafness, or blindness. Results: A total of 74 neonates were evaluated: 62 (83.8 %) with acute provoked NS (primarily hypoxic-ischaemic encephalopathy), and 12 (16.2 %) with neonatal-onset epilepsies (self-limited neonatal epilepsy, developmental and epileptic encephalopathy, cerebral malformations). Of these, 32 (43.2 %) had electrographic seizures, while 42 (56.7 %) had electroclinical seizures – 38 (90.5 %) were motor (42.1 % clonic) and 4 (9.5 %) were non-motor phenomena. Severe outcomes occurred in 33 of the 74 (44.6 %) participants. In multivariate analysis, neonatal-onset epilepsies (odds ratio [OR]: 1.3; 95 % confidence interval [CI]: 1.1–1.6), status epilepticus (OR: 5.4; 95 % CI: 1.5–19.9), and abnormal general movements (OR: 3.4; 95 % CI: 1.9–7.6) were associated with severe outcomes. Conclusions: At present, hypoxic-ischaemic encephalopathy remains the most frequent aetiology of NS. The prognosis of neonatal-onset epilepsies was worse than that of acute provoked NS, and status epilepticus was the most predictive factor for adverse outcomes.


2024 - Recovery of chronic motor neuropathy due to acute intermittent porphyria after givosiran treatment in a young boy: a case report [Articolo su rivista]
Mazzoli, M.; Ricci, A.; Vaudano, A. E.; Marcacci, M.; Marchini, S.; Bergonzini, P.; DI PIERRO, E.; Pischik, E.; Iughetti, L.; Pietrangelo, A.; Meletti, S.; Ventura, P.
abstract

BACKGROUND: We describe the first case of a pediatric patient with acute intermittent porphyria and severe chronic porphyric neuropathy treated with givosiran, a small-interfering RNA that drastically decreases delta-aminolevulinic acid production and reduces porphyric attacks’ recurrence. CASE REPORT: A 12-year-old male patient with refractory acute intermittent porphyria and severe porphyric neuropathy was followed prospectively for 12 months after givosiran initiation (subcutaneous, 2.5 mg/kg monthly). Serial neurological, structural, and resting-state functional magnetic resonance imaging (MRI) evaluations were performed, including clinical scales and neurophysiological tests. Delta-aminolevulinic acid urinary levels dropped drastically during treatment. In parallel, all the administered neurological rating scales and neurophysiological assessments showed improvement in all domains. Moreover, an improvement in central motor conduction parameters and resting-state functional connectivity in the sensory- motor network was noticed. At the end of the follow-up, the patient could walk unaided after using a wheelchair for 5 years. CONCLUSIONS: A clear beneficial effect of givosiran was demonstrated in our patient with both clinical and peripheral nerve neurophysiologic outcome measures. Moreover, we first reported a potential role of givosiran in recovering central motor network impairment in acute intermittent porphyria (AIP), which was previously unknown. This study provides Class IV evidence that givosiran improves chronic porphyric neuropathy.


2024 - Subtle impairment of neurodevelopment in infants with late fetal growth restriction [Articolo su rivista]
Lucaccioni, L.; Boncompagni, A.; Pugliese, M.; Talucci, G.; Della Casa, E.; Bertoncelli, N.; Coscia, A.; Bedetti, L.; Berardi, A.; Iughetti, L.; Ferrari, F.
abstract

Introduction: Children with late fetal growth restriction (FGR) are at high risk of being born small for gestational age (SGA). These categories of newborns are at increased risk for neurodevelopment impairment. The general movements assessment, in particular at fidgety age, has been used to predict neurological dysfunctions. This study aimed to evaluate growth recovery, presence of fidgety movements at 3 months, and neurodevelopmental outcome at 2 years of age in term late FGR infants and adequate for gestational age (AGA) controls. Methods: Prospective clinical evaluation. At 3 months auxological parameters (AP) and neurological examination were evaluated while at 24 months neurodevelopment outcome by Griffiths Mental Development Scales (GMDS-R) was evaluated. Results: 38 late FGR and 20 AGA controls completed the study. Despite a significant catch up, at 3 months 13% of late FGR presented at least one auxological parameter <3° percentile. Moreover, 23.7% of late FGR infants did not show fidgety movements compared to 100% AGA controls (p <.001). Cranial circumference at birth resulted a positive predictive factor for FMs (p =.039). At 2 years of age, a difference statistically significant between late FGR and AGA was detected in GMDS-R. Conclusion: Independently from growth recovery, fidgety movements resulted less expressed in late FGR infants, and at 2 years of age the neurodevelopmental assessment revealed differences in each domain of evaluation between late FGR and AGA infants, although within normal ranges.


2024 - The Changing Landscape of Neonatal Diabetes Mellitus in Italy Between 2003 and 2022 [Articolo su rivista]
Rapini, Novella; Delvecchio, Maurizio; Mucciolo, Mafalda; Ruta, Rosario; Rabbone, Ivana; Cherubini, Valentino; Zucchini, Stefano; Cianfarani, Stefano; Prandi, Elena; Schiaffini, Riccardo; Bizzarri, Carla; Piccini, Barbara; Maltoni, Giulio; Predieri, Barbara; Minuto, Nicola; Di Paola, Rossella; Giordano, Mara; Tinto, Nadia; Grasso, Valeria; Russo, Lucia; Tiberi, Valentina; Scaramuzza, Andrea; Frontino, Giulio; Maggio, Maria Cristina; Musolino, Gianluca; Piccinno, Elvira; Tinti, Davide; Carrera, Paola; Mozzillo, Enza; Cappa, Marco; Iafusco, Dario; Bonfanti, Riccardo; Novelli, Antonio; Barbetti, Fabrizio; Beccaria, Luciano; Candia, Francesco; Cauvin, Vittoria; Cardani, Roberta; Cardella, Francesca; Favia, Anna; Gallo, Francesco; Garzia, Patrizia; Ghirri, Paolo; Innaurato, Stefania; Iughetti, Lorenzo; Laforgia, Nicola; Lo Presti, Donatella; Marsciani, Alberto; Meschi, Franco; Panzeca, Rossana; Pasquino, Bruno; Pesavento, Roberta; Pezzino, Giulia; Reinstadler, Petra; Ripoli, Carlo; Savastio, Silvia; Timpanaro, Tiziana; Tumini, Stefano; Vento, Gianni
abstract

Context In the last decade the Sanger method of DNA sequencing has been replaced by next-generation sequencing (NGS). NGS is valuable in conditions characterized by high genetic heterogeneity such as neonatal diabetes mellitus (NDM).Objective To compare results of genetic analysis of patients with NDM and congenital severe insulin resistance (c.SIR) identified in Italy in 2003-2012 (Sanger) vs 2013-2022 (NGS).Methods We reviewed clinical and genetic records of 104 cases with diabetes onset before 6 months of age (NDM + c.SIR) of the Italian dataset.Results Fifty-five patients (50 NDM + 5 c.SIR) were identified during 2003-2012 and 49 (46 NDM + 3 c.SIR) in 2013-2022. Twenty-year incidence was 1:103 340 (NDM) and 1:1 240 082 (c.SIR) live births. Frequent NDM/c.SIR genetic defects (KCNJ11, INS, ABCC8, 6q24, INSR) were detected in 41 and 34 probands during 2003-2012 and 2013-2022, respectively. We identified a pathogenic variant in rare genes in a single proband (GATA4) (1/42 or 2.4%) during 2003-2012 and in 8 infants (RFX6, PDX1, GATA6, HNF1B, FOXP3, IL2RA, LRBA, BSCL2) during 2013-2022 (8/42 or 19%, P = .034 vs 2003-2012). Notably, among rare genes 5 were recessive. Swift and accurate genetic diagnosis led to appropriate treatment: patients with autoimmune NDM (FOXP3, IL2RA, LRBA) were subjected to bone marrow transplant; patients with pancreas agenesis/hypoplasia (RFX6, PDX1) were supplemented with pancreatic enzymes, and the individual with lipodystrophy caused by BSCL2 was started on metreleptin.Conclusion NGS substantially improved diagnosis and precision therapy of monogenic forms of neonatal diabetes and c.SIR in Italy.


2023 - Antibiotic Prophylaxis for the Prevention of Urinary Tract Infections in Children: Guideline and Recommendations from the Emilia-Romagna Pediatric Urinary Tract Infections (UTI-Ped-ER) Study Group [Articolo su rivista]
Autore, Giovanni; Bernardi, Luca; Ghidini, Filippo; La Scola, Claudio; Berardi, Alberto; Biasucci, Giacomo; Marchetti, Federico; Pasini, Andrea; Capra, Maria Elena; Castellini, Claudia; Cioni, Vera; Cantatore, Sante; Cella, Andrea; Cusenza, Francesca; De Fanti, Alessandro; Della Casa Muttini, Elisa; Di Costanzo, Margherita; Dozza, Alessandra; Gatti, Claudia; Malaventura, Cristina; Pierantoni, Luca; Parente, Giovanni; Pelusi, Gabriella; Perrone, Serafina; Serra, Laura; Torcetta, Francesco; Valletta, Enrico; Vergine, Gianluca; Antodaro, Francesco; Bergomi, Andrea; Chiarlolanza, Jennifer; Leoni, Laura; Mazzini, Franco; Sacchetti, Roberto; Suppiej, Agnese; Iughetti, Lorenzo; Pession, Andrea; Lima, Mario; Esposito, Susanna
abstract


2023 - Assessing risks of leaving the umbilical cord uncut: A case–control study [Articolo su rivista]
Bedetti, L.; Zinani, I.; Lugli, L.; Iughetti, L.; Facchinetti, F.; Berardi, A.
abstract


2023 - Blackwater Fever Treated with Steroids in Nonimmune Patient, Italy [Articolo su rivista]
Di Biase, Anna Rita; Buonfrate, Dora; Stefanelli, Francesca; Zavarise, Giorgio; Franceschini, Erica; Mussini, Cristina; Iughetti, Lorenzo; Gobbi, Federico
abstract

: Causes of blackwater fever, a complication of malaria treatment, are not completely clear, and immune mechanisms might be involved. Clinical management is not standardized. We describe an episode of blackwater fever in a nonimmune 12-year-old girl in Italy who was treated with steroids, resulting in a rapid clinical resolution.


2023 - Clinical Approach in the Management of Paediatric Patients with Familial Hypercholesterolemia: A National Survey Conducted by the LIPIGEN Paediatric Group [Articolo su rivista]
Pederiva, Cristina; Gazzotti, Marta; Arca, Marcello; Averna, Maurizio; Banderali, Giuseppe; Biasucci, Giacomo; Brambilla, Marta; Buonuomo, Paola Sabrina; Calabrò, Paolo; Cipollone, Francesco; Citroni, Nadia; D'Addato, Sergio; Del Ben, Maria; Genovesi, Simonetta; Guardamagna, Ornella; Iannuzzo, Gabriella; Iughetti, Lorenzo; Mandraffino, Giuseppe; Maroni, Lorenzo; Mombelli, Giuliana; Muntoni, Sandro; Nascimbeni, Fabio; Passaro, Angelina; Pellegatta, Fabio; Pirro, Matteo; Pisciotta, Livia; Pujia, Roberta; Sarzani, Riccardo; Scicali, Roberto; Suppressa, Patrizia; Zambon, Sabina; Zenti, Maria Grazia; Calandra, Sebastiano; Catapano, Alberico Luigi; Tarugi, Patrizia; Galimberti, Federica; Casula, Manuela; Capra, Maria Elena
abstract

: Detection and treatment of patients with familial hypercholesterolemia (FH) starting from childhood is fundamental to reduce morbidity and mortality. The activity of National realities such as the LIPIGEN (LIpid transPort disorders Italian GEnetic Network) Paediatric Group, founded in 2018, is a milestone in this context. The aim of this exploratory survey, conducted in October 2021 among Italian lipid clinics included in the LIPIGEN Paediatric Group, was to investigate the current clinical approach in the management and treatment of paediatric patients with suspected FH. A digital questionnaire composed of 20 questions investigating nutritional treatment and nutraceutical and pharmacological therapy for children and adolescents with FH was proposed to the principal investigators of 30 LIPIGEN centres. Twenty-four centres responded to the section referring to children aged < 10 years and 30 to that referring to adolescents. Overall, 66.7% of children and 73.3% of adolescents were given lipid-lowering nutritional treatment as the first intervention level for at least 3-4 months (29.2% and 23.3%) or 6-12 months (58.3% and 53.3%). Nutraceuticals were considered in 41.7% (regarding children) and 50.0% (regarding adolescents) of the centres as a supplementary approach to diet. Lipid-lowering drug therapy initiation was mainly recommended (91.7% and 80.0%). In 83.3% of children and 96.7% of adolescents, statins were the most frequently prescribed drug. We highlighted several differences in the treatment of paediatric patients with suspected FH among Italian centres; however, the overall approach is in line with the European Atherosclerosis Society (EAS) recommendations for FH children and adolescents. We consider this survey as a starting point to reinforce collaboration between LIPIGEN centres and to elaborate in the near future a consensus document on the management of paediatric patients with suspected FH so as to improve and uniform detection, management, and treatment of these patients in our country.


2023 - Continuous Fentanyl Infusion in Newborns with Hypoxic–Ischemic Encephalopathy Treated with Therapeutic Hypothermia: Background, Aims, and Study Protocol for Time-Concentration Profiles [Articolo su rivista]
Lugli, L.; Garetti, E.; Goffredo, B. M.; Candia, F.; Crestani, S.; Spada, C.; Guidotti, I.; Bedetti, L.; Miselli, F.; Della Casa, E. M.; Roversi, M. F.; Simeoli, R.; Cairoli, S.; Merazzi, D.; Lago, P.; Iughetti, L.; Berardi, A.
abstract

Therapeutic hypothermia (TH) is the standard of care for newborns with moderate to severe hypoxic–ischemic encephalopathy (HIE). Discomfort and pain during treatment are common and may affect the therapeutic efficacy of TH. Opioid sedation and analgesia (SA) are generally used in clinical practice, and fentanyl is one of the most frequently administered drugs. However, although fentanyl’s pharmacokinetics (PKs) may be altered by hypothermic treatment, the PK behavior of this opioid drug in cooled newborns with HIE has been poorly investigated. The aim of this phase 1 study protocol (Trial ID: FentanylTH; EUDRACT number: 2020-000836-23) is to evaluate the fentanyl time-concentration profiles of full-term newborns with HIE who have been treated with TH. Newborns undergoing TH receive a standard fentanyl regimen (2 mcg/Kg of fentanyl as a loading dose, followed by a continuous infusion—1 mcg/kg/h—during the 72 h of TH and subsequent rewarming). Fentanyl plasma concentrations before bolus administration, at the end of the loading dose, and 24-48-72-96 h after infusion are measured. The median, maximum, and minimum plasma concentrations, together with drug clearance, are determined. This study will explore the fentanyl time-concentration profiles of cooled, full-term newborns with HIE, thereby helping to optimize the fentanyl SA dosing regimen during TH.


2023 - COVID-19 restrictions and hygiene measures reduce the rates of respiratory infections and wheezing among preterm infants [Articolo su rivista]
Scarponi, D.; Bedetti, L.; Zini, T.; Di Martino, M.; Cingolani, G. M.; Spaggiari, E.; Rossi, K.; Miselli, F.; Lugli, L.; Bergamini, B. M.; Iughetti, L.; Berardi, A.
abstract

Background and aim: During the 2020 and 2021 Italian COVID-19 pandemic social restrictions and strict hygiene measures were recommended to limit the spread of SARS-CoV-2. We aimed to assess whether rates of respiratory infections and wheezing in preterm infants have changed during the pandemic. Methods: Single center, retrospective study. Preterm infants in the first 6 months of life discharged home prior to (Period 1, January 2017 - December 2019) or during the pandemic (Period 2, January 2020 - March 2021) were compared. Rates of respiratory infection and wheezing in preterm infants with or without bronchopulmonary dysplasia (BDP) were assessed. Results: During period 2 premature infants had lower rates of respiratory infections (36 out of 55 in Period 1 vs 11 out of 28 in Period 2, P=0.023) and wheezing (20 out of 55 in Period 1 vs 1 out of 28 in Period 2, P=0.001). This difference remained significant when infants with BPD (all grades) were analyzed separately (respiratory infections 26 out of 40 in Period 1 vs 7 out of 24 in Period 2, P=0.005; wheezing 16 out of 40 in Period 1 vs 1 out of 24 in Period 2, P=0.001). In contrast, respiratory infections and wheezing in preterm infants without BPD did not change after pandemic. Conclusions: Episodes of respiratory infections and wheezing among preterm infants were reduced during pandemic. We highlight the importance of proper family education for preventing respiratory tract infections in preterm infants with BPD, beyond the extraordinary conditions of the COVID-19 pandemic.


2023 - Deep phenotyping of the neuroimaging and skeletal features in KBG syndrome: a study of 53 patients and review of the literature [Articolo su rivista]
Peluso, Francesca; Caraffi, Stefano G; Contrò, Gianluca; Valeri, Lara; Napoli, Manuela; Carboni, Giorgia; Seth, Alka; Zuntini, Roberta; Coccia, Emanuele; Astrea, Guja; Bisgaard, Anne-Marie; Ivanovski, Ivan; Maitz, Silvia; Brischoux-Boucher, Elise; Carter, Melissa T; Dentici, Maria Lisa; Devriendt, Koenraad; Bellini, Melissa; Digilio, Maria Cristina; Doja, Asif; Dyment, David A; Farholt, Stense; Ferreira, Carlos R; Wolfe, Lynne A; Gahl, William A; Gnazzo, Maria; Goel, Himanshu; Grønborg, Sabine Weller; Hammer, Trine; Iughetti, Lorenzo; Kleefstra, Tjitske; Koolen, David A; Lepri, Francesca Romana; Lemire, Gabrielle; Louro, Pedro; Mccullagh, Gary; Madeo, Simona F; Milone, Annarita; Milone, Roberta; Nielsen, Jens Erik Klint; Novelli, Antonio; Ockeloen, Charlotte W; Pascarella, Rosario; Pippucci, Tommaso; Ricca, Ivana; Robertson, Stephen P; Sawyer, Sarah; Falkenberg Smeland, Marie; Stegmann, Sander; Stumpel, Constanze T; Goel, Amy; Taylor, Juliet M; Barbuti, Domenico; Soresina, Annarosa; Bedeschi, Maria Francesca; Battini, Roberta; Cavalli, Anna; Fusco, Carlo; Iascone, Maria; Van Maldergem, Lionel; Venkateswaran, Sunita; Zuffardi, Orsetta; Vergano, Samantha; Garavelli, Livia; Bayat, Allan
abstract

Background: KBG syndrome is caused by haploinsufficiency of ANKRD11 and is characterised by macrodontia of upper central incisors, distinctive facial features, short stature, skeletal anomalies, developmental delay, brain malformations and seizures. The central nervous system (CNS) and skeletal features remain poorly defined. Methods: CNS and/or skeletal imaging were collected from molecularly confirmed individuals with KBG syndrome through an international network. We evaluated the original imaging and compared our results with data in the literature. Results: We identified 53 individuals, 44 with CNS and 40 with skeletal imaging. Common CNS findings included incomplete hippocampal inversion and posterior fossa malformations; these were significantly more common than previously reported (63.4% and 65.9% vs 1.1% and 24.7%, respectively). Additional features included patulous internal auditory canal, never described before in KBG syndrome, and the recurrence of ventriculomegaly, encephalic cysts, empty sella and low-lying conus medullaris. We found no correlation between these structural anomalies and epilepsy or intellectual disability. Prevalent skeletal findings comprised abnormalities of the spine including scoliosis, coccygeal anomalies and cervical ribs. Hand X-rays revealed frequent abnormalities of carpal bone morphology and maturation, including a greater delay in ossification compared with metacarpal/phalanx bones. Conclusion: This cohort enabled us to describe the prevalence of very heterogeneous neuroradiological and skeletal anomalies in KBG syndrome. Knowledge of the spectrum of such anomalies will aid diagnostic accuracy, improve patient care and provide a reference for future research on the effects of ANKRD11 variants in skeletal and brain development.


2023 - Diprosopus: A Rare Case of Craniofacial Duplication and a Systematic Review of the Literature [Articolo su rivista]
Trevisani, V.; Balestri, E.; Napoli, M.; Caraffi, S. G.; Baroni, M. C.; Peluso, F.; Colonna, A.; Iughetti, L.; Gargano, G.; Superti-Furga, A.; Garavelli, L.
abstract

In 1990, Gorlin et al. described four types of craniofacial duplications: (1) single mouth with duplication of the maxillary arch; (2) supernumerary mouth laterally placed with rudimentary segments; (3) single mouth with replication of the mandibular segments; and (4) true facial duplication, namely diprosopus. We describe a newborn born with wide-spaced eyes, a very broad nose, and two separate mouths. Workup revealed the absence of the corpus callosum and the presence of a brain midline lipoma, wide sutures, and a Chiari I malformation with cerebellar herniation. We conducted a systematic review of the literature and compared all the cases described as diprosopus. In 96% of these, the central nervous system is affected, with anencephaly being the most commonly associated abnormality. Other associated anomalies include cardiac malformations (86%), cleft palate (63%), diaphragmatic hernia (13%), and disorder of sex development (DSD) (13%). Although the facial features are those that first strike the eye, the almost obligate presence of cerebral malformations suggests a disruptive event in the cephalic pole of the forming embryo. No major monogenic contribution has been recognized today for this type of malformation.


2023 - Early life exposure to phthalates and risk assessment: are we doing enough? [Abstract in Rivista]
De Pasquale, Lisa; Lugli, Camilla; Palandri, Lucia; Barbieri, Riccardo; Passini, Erica; Facchinetti, Fabio; Iughetti, Lorenzo; Lucaccioni, Laura; Righi, Elena
abstract

Background and Objective: Phthalates, potential endocrine disruptors with antiandrogenic effects, are widely used in several everyday products and are ubiquitous pollutants. Since 1999 European Authorities enacted several regulations to limit phthalate use and prevent exposure, mainly for more susceptible populations such as infants. This study aims to evaluate the estimated daily intake (EDI) of phthalates and to perform risk assessment evaluation in an Italian pediatric cohort. Methods: Between 2019 and 2020, 197 mother-child couples were enrolled in a prospective cohort study at the University Hospital of Modena (Italy). Urine samples were collected at birth, 3 and 6-months. 8 phthalates metabolites were analyzed. EDI was estimated and Risk quotients (RQ) were calculated using tolerable daily intake levels, (RQ(TDI)) as determined by the European Food Safety Authority, and the revised reference doses for anti-androgenicity RQ(RfD-AA), recently proposed. Finally, combined Hazard Indexes (HI) were calculated to assess synergic effect of different phthalates. Results: Most EDI and RQ(TDI) were lower than the acceptable values. The highest levels were found for Diethyl-phthalate (DEP), followed by Di-2-ethylhexyl-phthlate (DEHP). Newborns showed the highest values, followed by 6-months infants. Values exceeding the risk levels were observed for DEHP or di-n-butyl-phthalate (DnBP) in 5.5% and 10% of the newborns, respectively for RQ(RfDAA) and HI. Overall, HI higher values than threshold were observed at each follow-up visit. Conclusion: Since the European Union has a strict regulation policy regarding the most critical phthalates, these findings raise concern: exposure affecting children in Modena is still spread and includes phthalates banned in childcare products, such as DEHP and DnBP. Notably, few infants (especially newborns) exceeded the risk threshold for antiandrogenic effects. Further, exposure patterns seem to change over time during their first months of life. More extensive public health measures need to be planned to efficiently protect the most sensitive subgroups, including infants.


2023 - Early-life exposure to phthalates and minipuberty: is there any relationship? [Abstract in Rivista]
Lucaccioni, L; Palandri, L; Trevisani, V; Righi, B; Calandra Bonaura, F; Predieri, B; Righi, E; Iughetti, L
abstract


2023 - Effects of the COVID-19 pandemic on anthropometric data, glycemic control, and lipid levels in children and young people with type 1 diabetes: two years of follow-up [Abstract in Rivista]
Iughetti, L; Candia, F; Stefanelli, F; Trevisani, V; Madeo, Sf; Bruzzi, P; Predieri, B
abstract


2023 - Endocrine immune-related adverse effects of immune-checkpoint inhibitors [Articolo su rivista]
Trevisani, Viola; Iughetti, Lorenzo; Lucaccioni, Laura; Predieri, Barbara
abstract

IntroductionImmune-checkpoint inhibitor therapy modulates the response of the immune system acting against cancer. Two pathways impacted by this kind of treatment are the CTLA4 and the PD-1/PD-L1 pathways. ICI therapy can trigger autoimmune adverse effects, known as immune-related Adverse Events (irAEs).Areas coveredThis review focuses on irAEs which affect the endocrine system. This review elucidates the pathways used by these drugs with a focus on the hypothetical pathogenesis at their basis. In fact, the pathophysiology of irAEs concerns the possibility of an interaction between cellular autoimmunity, humoral immunity, cytokines, chemokines, and genetics. The endocrine irAEs examined are thyroid dysfunctions, immune related-hypophysitis, diabetes, peripheral adrenal insufficiency, and hypoparathyroidism.Expert opinionThere is still much to investigate in endocrine irAES of checkpoint inhibitors. In the future, checkpoint inhibitors will be increasingly utilized therapies, and therefore it is crucial to find the proper diagnostic-therapeutic program for irAEs, especially as endocrine irAEs are nonreversible and require lifelong replacement therapies.


2023 - From Metabolic Syndrome to Type 2 Diabetes in Youth [Articolo su rivista]
Iafusco, Dario; Franceschi, Roberto; Maguolo, Alice; Guercio Nuzio, Salvatore; Crinò, Antonino; Delvecchio, Maurizio; Iughetti, Lorenzo; Maffeis, Claudio; Calcaterra, Valeria; Manco, Melania
abstract

In the frame of metabolic syndrome, type 2 diabetes emerges along a continuum of the risk from the clustering of all its components, namely visceral obesity, high blood pressure and lipids, and impaired glucose homeostasis. Insulin resistance is the hallmark common to all the components and, in theory, is a reversible condition. Nevertheless, the load that this condition can exert on the beta-cell function at the pubertal transition is such as to determine its rapid and irreversible deterioration leading to plain diabetes. The aim of this review is to highlight, in the context of metabolic syndrome, age-specific risk factors that lead to type 2 diabetes onset in youth; resume age specific screening and diagnostic criteria; and anticipate potential for treatment. Visceral obesity and altered lipid metabolism are robust grounds for the development of the disease. Genetic differences in susceptibility to hampered beta-cell function in the setting of obesity and insulin resistance largely explain why some adolescents with obesity do develop diabetes at a young age and some others do not. Lifestyle intervention with a healthy diet and physical activity remains the pillar of the type 2 diabetes treatment in youth. As to the pharmacological management, metformin and insulin have failed to rescue beta-cell function and to ensure long-lasting glycemic control in youth. A new era might start with the approval for use in pediatric age of drugs largely prescribed in adults, such as dipeptidyl peptidase-4 and sodium-dependent glucose transport inhibitors, and of new weight-lowering drugs in the pipeline such as single and multiple agonists of the glucagon-like peptide 1 receptor. The latter drugs can have tremendous impact on the natural history of the disease. By treating diabetes, they will reduce the burden of all the metabolic abnormalities belonging to the syndrome while causing a tremendous weight loss hitherto never seen before.


2023 - How do Italian pediatric endocrinologists approach gender incongruence? [Articolo su rivista]
Ciancia, S.; Iughetti, L.
abstract

Background: Gender incongruence (GI) is a term used to describe a marked and persistent incompatibility between the sex assigned at birth (SAAB) and the experienced gender. Some persons presenting with GI experience a severe psychological distress defined as gender dysphoria (GD). Although the prevalence of GI is probably underestimated, recently a great increase in numbers of transgender and gender diverse (TGD) youths presenting at the gender clinics has been registered. After a careful multidisciplinary evaluation and upon acquisition of informed consent from the youth and the legal guardian(s), puberty suppression can be started in TGD youths, followed by the addition of gender affirming hormones (GAH) by the age of 16 years. Although Italian specific guidelines are available, their application is often complex because of (among other reasons) lack of specialized centers and healthcare professional with experience in the field and the regional differences within the Italian healthcare system. Main body: To investigate the care offered to TGD youths across Italy, we proposed a survey of 20 questions to the directors of the 32 Italian Centers of pediatric endocrinology participating to the Study Group on Growth and Puberty of the Italian Society of Pediatric Endocrinology (ISPED). Eighteen pediatric endocrinologists representative of 16 different centers belonging to 11 different regions responded to the survey. In the large majority of centers TGD youths are taken in charge between the age of 12 and 18 years and at least three healthcare professional are involved. Most of Italian pediatric endocrinologists follow only a very limited number of TGD youths and reference centers for TGD youths are lacking. Conclusion: There is an urgent need for gender clinics (homogeneously distributed on the national territory) where TGD youths can access high standard care.


2023 - Infectious Risks Related to Umbilical Venous Catheter Dwell Time and Its Replacement in Newborns: A Narrative Review of Current Evidence [Articolo su rivista]
Corso, L.; Buttera, M.; Candia, F.; Sforza, F.; Rossi, K.; Lugli, L.; Miselli, F.; Bedetti, L.; Baraldi, C.; Lucaccioni, L.; Iughetti, L.; Berardi, A.
abstract

The use of umbilical venous catheters (UVCs) has become the standard of care in the neonatal intensive care unit (NICU) to administer fluids, medications and parenteral nutrition. However, it is well known that UVCs can lead to some serious complications, both mechanical and infective, including CLABSI (Central Line-Associated Bloodstream Infections). Most authors recommend removing UVC within a maximum of 14 days from its placement. However, the last Infusion Therapy Standards of Practice (INS) guidelines recommends limiting the UVC dwell time to 7 to 10 days, to reduce risks of infectious and thrombotic complications. These guidelines also suggest as an infection prevention strategy to remove UVC after 4 days, followed by the insertion of a PICC if a central line is still needed. Nevertheless, the maximum UVC dwell time to reduce the risk of CLABSI is still controversial, as well as the time of its replacement with a PICC. In this study we reviewed a total of 177 articles, found by using the PubMed database with the following search strings: “UVC AND neonates”, “(neonate* OR newborn*) AND (UVC OR central catheter*) AND (infection*)”. We also analyze the INS guidelines to provide the reader an updated overview on this topic. The purpose of this review is to give updated information on CVCs infectious risks by examining the literature in this field. These data could help clinicians in deciding the best time to remove or to replace the UVC with a PICC, to reduce CLABSIs risk. Despite the lack of strong evidence, the risk of CLABSI seems to be minimized when UVC is removed/replaced within 7 days from insertion and this indication is emerging from more recent and larger studies.


2023 - La disforia di genere in età pediatrica e adolescenziale [Articolo su rivista]
Iughetti, L; Ciancia, S
abstract

While the sex of an individual refers to his/her genetic and anatomical characteristics, gender concerns the perception of oneself, personal and private, as belonging to the male or female gender, to both or neither. Generally gender perception between 3 and 7 years of age. Gender incongruence is defined by the absence of concordance between these two aspects, while gender dysphoria refers to the psychological distress that can follow. The number of children and adolescents showing gender incongruence is increasing and poses problems of diagnosis and treatment. Providing care requires the presence of a multidisciplinary team made up of expert professionals trained in this field, which should include neurospichiatrists, psychologists and pediatric endocrinologists. Pharmacological therapy, that follows a phase of psychotherapy, should be started in puberty and is preliminary to subsequent therapeutic interventions; the latter ones are prerogative of adulthood. A careful multidisciplinary follow-up is needed for these patients until adulthood.


2023 - Lipoprotein(a) Genotype Influences the Clinical Diagnosis of Familial Hypercholesterolemia [Articolo su rivista]
Olmastroni, Elena; Gazzotti, Marta; Averna, Maurizio; Arca, Marcello; Tarugi, Patrizia; Calandra, Sebastiano; Bertolini, Stefano; Catapano, Alberico L; Casula, Manuela; Marcello, Arca; Laura, D'Erasmo; Maurizio, Averna; Angelo Baldassare Cefalù, ; Andrea, Bartuli; Paola Sabrina Buonuomo, ; Andrea, Benso; Guglielmo, Beccuti; Giacomo, Biasucci; Maria Elena Capra, ; Gianni, Biolo; Pierandrea, Vinci; Luca, Bonanni; Claudio, Borghi; Sergio, D'Addato; Antonio Carlo Bossi, ; Giancarla, Meregalli; Adriana, Branchi; Paolo, Calabrò; Carubbi, Francesca; Nascimbeni, Fabio; Francesco, Cipollone; Marco, Bucci; Nadia, Citroni; Maria Del Ben, ; Francesco, Baratta; Massimo, Federici; Martina, Montagna; Claudio, Ferri; Serena, Notargiacomo; Anna Maria Fiorenza, ; Emanuela, Colombo; Giuliana, Fortunato; Maria Donata Di Taranto, ; Andrea, Giaccari; Simona, Moffa; Francesco, Giorgino; Sergio Di Molfetta, ; Ornella, Guardamagna; Luisa De Sanctis, ; Arcangelo, Iannuzzi; Raimondo, Cavallaro; Gabriella, Iannuzzo; Marco, Gentile; Iughetti, Lorenzo; Bruzzi, Patrizia; Salvatore, Lia; Alessandro, Lupi; Giuseppe, Mandraffino; Arianna, Toscano; Rossella, Marcucci; Martina, Berteotti; Lorenzo, Maroni; Fabiana, Locatelli; Tiziana, Montalcini; Giuliana, Mombelli; Sandro, Muntoni; Davide, Baldera; Gianfranco, Parati; Angelina, Passaro; Valerio, Pecchioli; Cristina, Pederiva; Giuseppe, Banderali; Antonio, Pipolo; Debora, D'Elia; Matteo, Pirro; Vanessa, Bianconi; Livia, Pisciotta; Elena, Formisano; Francesco, Purrello; Roberto, Scicali; Elena, Repetti; Elena, Cantino; Elisabetta, Rinaldi; Elena, Sani; Riccardo, Sarzani; Francesco, Spannella; Francesco, Sbrana; Beatrice Dal Pino, ; Patrizia, Suppressa; Cocco, VERONICA MARGHERITA; Chiara, Trenti; Emanuele Alberto Negri, ; Josè Pablo Werba, ; Alessandra, Romandini; Sabina, Zambon; Alberto, Zambon; Maria Grazia Zenti, ; Giulia, Fainelli; Fabio, Pellegatta; Liliana, Grigore; Katia, Bonomo; Eleonora, Capatti; Ada, Cutolo; Fabio, Fimiani; Simonetta, Genovesi; Sandro, Inchiostro; Chiara, Pavanello; Roberta, Pujia; Alon, Schaffer; Stefano, Bertolini; CALANDRA BUONAURA, Sebastiano; Alberico Luigi Catapano, ; Manuela, Casula; Elena, Olmastroni; Tarugi, Patrizia Maria; Marta, Gazzotti; Federica, Galimberti
abstract

BackgroundEvidence suggests that LPA risk genotypes are a possible contributor to the clinical diagnosis of familial hypercholesterolemia (FH). This study aimed at determining the prevalence of LPA risk variants in adult individuals with FH enrolled in the Italian LIPIGEN (Lipid Transport Disorders Italian Genetic Network) study, with (FH/M+) or without (FH/M-) a causative genetic variant. Methods and ResultsAn lp(a) [lipoprotein(a)] genetic score was calculated by summing the number risk-increasing alleles inherited at rs3798220 and rs10455872 variants. Overall, in the 4.6% of 1695 patients with clinically diagnosed FH, the phenotype was not explained by a monogenic or polygenic cause but by genotype associated with high lp(a) levels. Among 765 subjects with FH/M- and 930 subjects with FH/M+, 133 (17.4%) and 95 (10.2%) were characterized by 1 copy of either rs10455872 or rs3798220 or 2 copies of either rs10455872 or rs3798220 (lp(a) score >= 1). Subjects with FH/M- also had lower mean levels of pretreatment low-density lipoprotein cholesterol than individuals with FH/M+ (t test for difference in means between FH/M- and FH/M+ groups <0.0001); however, subjects with FH/M- and lp(a) score >= 1 had higher mean (SD) pretreatment low-density lipoprotein cholesterol levels (223.47 [50.40] mg/dL) compared with subjects with FH/M- and lp(a) score=0 (219.38 [54.54] mg/dL for), although not statistically significant. The adjustment of low-density lipoprotein cholesterol levels based on lp(a) concentration reduced from 68% to 42% the proportion of subjects with low-density lipoprotein cholesterol level >= 190 mg/dL (or from 68% to 50%, considering a more conservative formula). ConclusionsOur study supports the importance of measuring lp(a) to perform the diagnosis of FH appropriately and to exclude that the observed phenotype is driven by elevated levels of lp(a) before performing the genetic test for FH.


2023 - Malarial retinopathy in a preschool child: A case report with long-term paediatric and ophthamological follow-up [Articolo su rivista]
Lazzerini, A.; Sforza, F.; Fornasari, E.; Mastropasqua, R.; Bergonzini, P.; Iughetti, L.; Cavallini, G. M.
abstract

Aim: To report a paediatric case of retinopathy-positive cerebral malaria, emphasizing the clinical significance of long-term neurological and ophthalmological follow-up (5,5 years). Case report: After a recent journey in Ghana, a 17-month-old African female child was admitted at the Paediatric Emergency Room with fever and vomiting. Blood smear confirmed a Plasmodium Falciparum parasitaemia. Iv quinine was promptly administered, but after a few hours, the child developed generalized seizures, requiring benzodiazepine therapy and assisted ventilation for severe desaturation. Brain imaging (CT and MRI), lumbar puncture and several electroencephalograms showed data compatible with cerebral involvement of malaria. Schepens ophthalmoscopy and Ret-Cam pictures acquisition revealed macular haemorrhages in the left eye with central whitening and bilateral capillary abnormalities, typical signs of malarial retinopathy. Antimalarial therapy and iv Levetiracetam allowed neurological improvement. Eleven days after the admission, the child was discharged, showing no neurological symptoms and with an improved EEG signal, a normalized fundus oculi and brain imaging. Neurological and ophthalmological long-term follow-up were conducted: EEG controls didn’t reveal abnormalities and the complete ophthalmological assessment showed a regular visual acuity and fundus oculi, as well as a normal SD-OCT and electrophysiologic testing. Conclusion: Cerebral malaria is a severe complication, characterized by a high fatality rate and challenging diagnosis. A helpful instrument for diagnostic and prognostic evaluation is the ophthalmological detection of malarial retinopathy and its monitoring over time. In our patient the long term visual follow-up didn’t reveal any adverse outcome.


2023 - Maternal phthalate exposure and dietary habits during pregnancy: what do we need to look for? [Abstract in Rivista]
Scasserra, Maria; Maione, Domenico; Palandri, Lucia; De Pasquale, Lisa; Casalucci, Marta; Uguzzoni, Francesco; Lorenzon, Antonio; Facchinetti, Fabio; Iughetti, Lorenzo; Trevisani, Viola; Arletti, Maria; Lucaccioni, Laura; Righi, Elena
abstract

Background and Objectives: Phthalates are chemical products widely used as plasticizers, potentially harmful, especially for their antiandrogenic effects in specific populations, such as pregnant women and newborns. Ingestion is an important exposure pathway, however specific exposure sources and drivers are mainly unknown. The aim of this study was to evaluate the association between dietary and cooking habits during pregnancy and phthalates exposure at delivery. Methods: 197 women were recruited after delivery, in a single-center prospective cohort study at Modena’s University Hospital (Italy), from January 2019 to October 2020. Exposure to 6 phthalates was assessed in urine samples and expressed as µg/g of urinary creatinine. Pregnancy, dietary and cooking habits were recorded by ad hoc questionnaire. Descriptive statistics and bivariate analyzes were performed. Results: Overall, exposure resulted widespread in women at delivery. In women usually boiling food, urinary levels of Monobenzylphthalate (MBzP) (3.4±2 vs 4.7±3.3 μg/g) and Mono-2-ethylhexylphthalate (MEHP) (2.3±1.8 vs 5.2±15.2 μg/g) were significantly lower, whereas in women usually frying food, monon-butylphthalate (MnBP) appeared significantly higher (23.2±59.6 vs 9.8±11.5 μg/g). Low fruit consumption during pregnancy was associated with higher MnBP concentrations compared to daily consumption (39.3±83.1 vs 10.6±11.5 μg/g). Concentrations of monoethylphthalate (MEP) appeared higher in women who consumed cheese, eggs and fish. Daily consumption of red meat, beef and pork was associated with higher levels of di(2-ethylhexyl)phthalate (DEHP) metabolites. Conclusion: No strong association among exposure and dietary habits was observed, even though urinary levels of some phthalates resulted higher in women frequently consuming fat food and lower when consuming fruits or choosing healthier cooking methods. Surprisingly, no correlation appeared with packaged foods and packaging material. Further studies are needed to better elucidate ingestion exposure pathways with a greater focus on alternative sources of contamination such as food production, processing and transportation to better guide evidence-based policy making.


2023 - Medicina dell’adolescenza [Articolo su rivista]
Bertelloni, S; Chiarelli, F; Iughetti, L
abstract

L’Organizzazione Mondiale della Sanità definisce come “adolescenti” le persone di età compresa tra 10 e 19 anni. Questi minori rappresentano circa il 10-25% della popolazione a seconda dei vari paesi europei (www.euro.who.int) e poco più del 9,0% in Italia al 1° gennaio 2023 (www.istat.it). Nel nostro Paese si osserva inoltre una rapida contrazione dei soggetti in età adolescenziale in conseguenza del progressivo calo delle nascite; ad esempio, si ha una riduzione di oltre l’8% (-47.165 unità) dei bambini di 10 anni rispetto ai ragazzi di 18 anni. Una prima ovvia considerazione a questo dato di fatto è la necessità di assicurare il migliore stato possibile a questa fascia di età anche in prospettiva futura. In effetti, la maggior parte degli adolescenti in Europa è sana, ma ogni giorno oltre 3.000 di loro muoiono per cause prevenibili o curabili. Inoltre, gli adolescenti presentano cause specifiche di morbilità [lesioni non intenzionali o intenzionali, disturbi della salute mentale (depressione, abuso di sostanze, disturbi alimentari), malattie infettive, comportamenti sessuali a rischio, gravidanza e parto precoci] con conseguenze sia a breve che a lungo termine (Slobođanac M., et al. www.eapaediatrics.eu/young-eap-eap-july-2019-blog-adolescent-medicine-and-health-a-training-challenge-for-europe/). Ne deriva la necessità di percorsi formativi dedicati pre-laurea e post-laurea, compresi quelli di educazione medica continua, in Medicina dell’adolescenza. Alcuni paesi (USA, Canada, Australia) hanno riconosciuto le esigenze specifiche di salute degli adolescenti, creando percorsi formativi anche specialistici in questo nuovo settore medico.


2023 - Nationwide survey on the management of pediatric pharyngitis in Italian emergency units [Articolo su rivista]
Milani, G. P.; Rosa, C.; Tuzger, N.; Alberti, I.; Ghizzi, C.; Zampogna, S.; Amigoni, A.; Agostoni, C.; Peroni, D.; Marchisio, P.; Chiappini, E.; Tappi, E.; Rabbone, I.; Salvini, F. M.; Cozzi, G.; Silvagni, D.; Pitea, M.; Manieri, S.; Crisalfi, A.; Vaccaro, A.; Plebani, A. M.; Falorni, S.; Martelli, L.; Lanari, M.; Di Stefano, G.; De Martinis, M.; Bulciolu, P.; Iughetti, L.; Fabiani, E.; Greco, R.; Cardinale, F.; Boera, R.; Arrighini, A.; Chiaretti, A.; Nunziata, F.; Salvo, R.; Banderali, G.; Fasoli, S.; Baracchia, G.; Antonucci, R.; Biondi, A.; Tenci, A.; Mirri, G.; Battisti, L.; Bellettato, M.; Ruffini, E.; Cogo, P.; Dragovic, D.; Da Dalt, L.; Bruni, P.; Caloiero, M.; Varisco, T.; Palmieri, M.; Picciotti, E.; Cualbu, A.; Pradal, U.; Grosso, S.; Pogliani, L. M.; Selicorni, A.; Soffiati, M.; Bene, P.; Guala, A.; Bertolozzi, G.; Tommasi, P.; Campanozzi, A.; Cella, A.; Ghitti, C.; Groff, P.; Bondone, C.; Vitale, A.; Capalbo, P. T.; Dall'Amico, R.; Sisto, A.; Livio, E. L.; Tato, E.; Flora, M.; Raiola, G.; Suppiej, A.; Clemente, C.; Lizzoli, F.; Chiarelli, F.; Podesta, A.; Forte, F. R.; Vasarri, P.; Pennoni, G.; Parrinello, F.; Fornaro, M.; Casa, R.; Bondone, C.; Zaglia, F.; Tipo, V.; Morandi, F.; Cecinati, V.; Calabro, G.; Messini, B.; Marseglia, G. L.; Arrigoni, S.; Gaggiano, S.; Cavalli, C.; Gramaglia, G.; Serra, L.; Valletta, E.; Militerno, G.; Chiossi, M.; Camellino, G.; Masi, S.; Marchetti, F.; Traina, G.; Maccarrone, R. M.
abstract

Background: Acute pharyngitis is a frequent reason for primary care or emergency unit visits in children. Most available data on pharyngitis management come from primary care studies that demonstrate an underuse of microbiological tests, a tendency to over-prescribe antibiotics and a risk of antimicrobial resistance increase. However, a comprehensive understanding of acute pharyngitis management in emergency units is lacking. This study aimed to investigate the frequency of rapid antigen test use to diagnose acute pharyngitis, as well as other diagnostic approaches, the therapeutic attitude, and follow-up of children with this condition in the emergency units. Methods: A multicentric national study was conducted in Italian emergency departments between April and June 2022. Results: A total of 107 out of 131 invited units (response rate 82%), participated in the survey. The results showed that half of the units use a scoring system to diagnose pharyngitis, with the McIsaac score being the most commonly used. Most emergency units (56%) were not provided with a rapid antigen diagnostic test by their hospital, but the test was more frequently available in units visiting more than 10,000 children yearly (57% vs 33%, respectively, p = 0.02). Almost half (47%) of the units prescribe antibiotics in children with pharyngitis despite the lack of microbiologically confirmed cases of Group A β-hemolytic streptococcus. Finally, about 25% of units prescribe amoxicillin-clavulanic acid to treat Group A β-hemolytic streptococcus pharyngitis. Conclusions: The study sheds light on the approach to pharyngitis in emergency units, providing valuable information to improve the appropriate management of acute pharyngitis in this setting. The routinary provision of rapid antigen tests in the hospitals could enhance the diagnostic and therapeutic approach to pharyngitis.


2023 - Neuropsychological Outcomes of Children Treated for Brain Tumors [Articolo su rivista]
Pancaldi, Alessia; Pugliese, Marisa; Migliozzi, Camilla; Blom, Johanna; Cellini, Monica; Iughetti, Lorenzo
abstract

Central nervous system (CNS) neoplasms are the most common solid tumors diagnosed in children. CNS tumors represent the leading cause of cancer death and cancer-related morbidity for children less than 20 years of age, although there has been a moderate increase in survival rates over the past several decades. The average survival at 5 years now nearly reaches 75%, and for some, non-malignant histology approximates 97% at 20 years from diagnosis. Neurological, cognitive, and neuropsychological deficits are the most disabling long-term effects of brain tumors in children. Childhood is a time of extreme brain sensitivity and the time of life in which most brain development occurs. Thus, the long-term toxicities that children treated for CNS tumors experience can affect multiple developmental domains and day-to-day functioning, ultimately leading to a poor quality of survival (QoS). We reviewed literature focusing on the risk factors for cognitive and neuropsychological impairment in pediatric patients treated for brain tumors with the aim of better understanding who is at major risk and what the best strategies for monitoring these patients are.


2023 - Parenting stress: socio-economic determinants before and during the covid-19 pandemic. results of an italian cross-sectional study [Abstract in Rivista]
Fasano, Marco; Iughetti, Lorenzo; Palandri, Lucia; Pasquale, Lisa; Ferrari, Eleonora; Trevisani, Viola; Passini, Erica; Lucaccioni, Laura; Righi, Elena
abstract

Background and objective: Parenting can be a stressful experience and in the context of a pandemic it can represent a challenge for many families. The aim of this study was to investigate socio-demographic factors related to parenting stress before and after the SARS-CoV-2 outbreak in Italian parents living in Modena (Italy). Methods: From September 2019 to May 2021, 80 parents of 6 months healthy children were enrolled in a prospective cohort study at the local University Hospital and filled in the Parenting Stress Index Short Form (PSI-SF), a validated questionnaire measuring parenting stress, well-known in clinical practice for its reliability and simplicity of use. PSI scores over the 90th percentile of the Italian population distribution were considered indicative of a highly stressful condition. The role played by different socio-demographic factors in increasing PSI score was tested by chi-square test in the whole sample and by stratifying parents according to the evaluation time (PRE-COVID and COVID period). Results: Overall, 11% of parents reported high stress scores and prevalence was higher during lockdown (15% vs 6%). In the COVID group, higher scores were observed in younger mothers (17%), higher educated parents (16% and 23% of mothers and fathers respectively), having only one child (18%) and living in the urban environment (23%), regardless of infant’s gender. In the PRE-COVID group higher stress scores were reported mainly by parents with more than one child (10%), with male children (9%), and by mothers with lower education (8%). Nevertheless, differences were often not statistically significant. Conclusion: Different socio-demographic factors appear to be related to higher parenting stress and our results suggest that they could show inverse trends in different conditions. Parenting stress in difficult circumstances must be addressed carefully and promptly and specific public health interventions for families with special needs must be planned and implemented.


2023 - Perinatal and postnatal exposure to phthalates and early neurodevelopment at 6 months in healthy infants born at term [Articolo su rivista]
Lucaccioni, Laura; Palandri, Lucia; Passini, Erica; Trevisani, Viola; Calandra Buonaura, Filippo; Bertoncelli, Natascia; Talucci, Giovanna; Ferrari, Angela; Ferrari, Eleonora; Predieri, Barbara; Facchinetti, Fabio; Iughetti, Lorenzo; Righi, Elena
abstract

Background: Phthalates are non-persistent chemicals largely used as plasticizers and considered ubiquitous pollutants with endocrine disrupting activity. The exposure during sensible temporal windows as pregnancy and early childhood, may influence physiological neurodevelopment. Aims and Scope: The aim of this study is to analyze the relationship between the urinary levels of phthalate metabolites in newborn and infants and the global development measured by the Griffiths Scales of Children Development (GSCD) at six months. Methods: Longitudinal cohort study in healthy Italian term newborn and their mothers from birth to the first 6 months of life. Urine samples were collected at respectively 0 (T0), 3 (T3), 6 (T6) months, and around the delivery for mothers. Urine samples were analyzed for a total of 7 major phthalate metabolites of 5 of the most commonly used phthalates. At six months of age a global child development assessment using the third edition of the Griffith Scales of Child Development (GSCD III) was performed in 104 participants. Results: In a total of 387 urine samples, the seven metabolites analyzed appeared widespread and were detected in most of the urine samples collected at any time of sampling (66-100%). At six months most of the Developmental Quotients (DQs) falls in average range, except for the subscale B, which presents a DQ median score of 87 (85-95). Adjusted linear regressions between DQs and urinary phthalate metabolite concentrations in mothers at T0 and in infants at T0, T3 and T6 identified several negative associations both for infants’ and mothers especially for DEHP and MBzP. Moreover, once stratified by children’s sex, negative associations were found in boys while positive in girls. Conclusions: Phthalates exposure is widespread, especially for not regulated compounds. Urinary phthalate metabolites were found to be associated to GSCD III scores, showing inverse association with higher phthalate levels related to lower development scores. Our data suggested differences related to the child’s sex.


2023 - Progressive osseous heteroplasia: A case report with an unexpected trigger [Articolo su rivista]
Boncompagni, A.; Lucas-Herald, A. K.; Beattie, P.; Mcdevitt, H.; Iughetti, L.; Constantinou, P.; Kinning, E.; Ahmed, S. F.; Mason, A.
abstract

Progressive osseous heteroplasia (POH) is a rare genetic disorder characterised by progressive heterotopic ossification (HO) within the skin and subcutaneous tissues. The condition is caused by heterozygous inactivating mutations of the GNAS gene and usually presents in infancy. We describe the case of a white male ex-preterm who was first referred because of subcutaneous calcium deposits along the right arm after extravasation of parenteral nutrition. As these lesions progressed, a skin biopsy was undertaken which revealed intramembranous ossification. Genetic testing revealed a constitutional, de novo, heterozygous, nonsense variant in the GNAS gene that has not previously been described, but which is consistent with patient's clinical diagnosis of POH. No endocrine abnormalities or other signs congruent with overlapping conditions were detected. To the best of our knowledge, this is the first case describing an inflammatory trigger in POH. Trials with intravenous bisphosphonate and glucocorticoid as well as with topical sodium thiosulphate were attempted without clinical improvement. Excision of the calcifications and physiotherapy seem to have provided a partial improvement on mobility of the elbow. This case widens the spectrum of phenotypes seen in GNAS mutation disorders and suggests that alternative anti-inflammatory treatments may be effective. Mutations in GNAS should be considered in cases of significant progressive calcium deposition after extravasation injury.


2023 - Pyomyositis associated with abscess formation caused by streptococcus pneumoniae in children: a case report and review of literature [Articolo su rivista]
Barchi, L.; Fastiggi, M.; Bassoli, I.; Bonvicini, F.; Silvotti, M.; Iughetti, L.; De Fanti, A.
abstract

Background: Pyomyositis is an unusual bacterial infection but potential severe in children. Staphylococcus Aureus is the main caused of this disease (70–90%), following by Streptococcus Pyogenes (4–16%). Streptococcus Pneumoniae rarely caused invasive muscular infections. We describe a case of pyomyositis caused by Streptococcus Pneumonia in an adolescent 12-year-old female. Case presentation: I.L. referred to our hospital for high fever associated with right hip and abdominal pain. The blood exams showed increase of leukocytes with prevalence of neutrophils with high level of inflammatory markers (CRP 46,17 mg/dl; Procalcitonin 25,8 ng/ml). The abdomen ultrasonography was unremarkable. The CT and MRI of the abdomen and right hip revealed pyomyositis of the iliopsoas, piriformis and internal shutter associated with collection of pus between the muscular planes (Fig. 1). The patient was admitted to our paediatric care unit, and she was initially treatment with intravenous Ceftriaxone (100 mg/kg/day) and Vancomycin (60 mg/kg/day). On day 2, a pansensitive Streptococcus Pneumoniae was isolated from the blood culture, and the antibiotic treatment was changed to only IV Ceftriaxone. She was successively treated with IV Ceftriaxone for 3 weeks, then continued with oral Amoxicillin for a total of 6 weeks of therapy. The follow up showed a complete resolution of the pyomyositis and psoas abscess after 2 months. Conclusion: Pyomyositis associate with abscess is a rare and very dangerous disease in children. The clinical presentation can mimic symptoms of other pathologies like osteomyelitis or septic arthritis, so many times is hard to identify. The main risk factors include story of recent trauma and immunodeficiency, not present in our case report. The therapy involves the antibiotics and, if possible, abscess drainage. In literature there is much discussion about duration of antibiotic therapy.


2023 - Real life long-term efficacy and safety of rhGH therapy in children with SHOX deficiency [Articolo su rivista]
Bruzzi, Patrizia; Vannelli, Silvia; Scarano, Emanuela; Di Iorgi, Natascia; Parpagnoli, Maria; Salerno, Mariacarolina; Pitea, Marco; Street, Maria Elisabeth; Secco, Andrea; Trettene, Adolfo Andrea; Wasniewska, Malgorzata; Corciulo, Nicola; Tornese, Gianluca; Faienza, Maria Felicia; Delvecchio, Maurizio; Madeo, Simona Filomena; Iughetti, Lorenzo
abstract

Objective: This Italian survey aims to evaluate real-life long-term efficacy and safety of rhGH therapy in children with short stature homeobox-containing gene deficiency disorders (SHOX-D) and to identify potential predictive factors influencing response to rhGH therapy. Design and methods: This is a national retrospective observational study collecting anamnestic, anthropometric, clinical, instrumental and therapeutic data in children and adolescents with a genetic confirmation of SHOX-D treated on rhGH. Data were collected at the beginning of rhGH therapy (T0), yearly during the first 4 years of rhGH therapy (T1, T2, T3, T4) and at near-final height (nFH) (T5), when available. Results: 117 SHOX-D children started rhGH therapy (initial dose 0.23 ± 0.04 mg/kg/week) at a mean age of 8.67 ± 3.33years (74% prepubertal), 99 completed the 1st year of treatment, and 46 reached nFH. During rhGH therapy, growth velocity (GV) SDS and height (H) SDS improved significantly. Mean H SDS gain from T0 was +1.14±0.58 at T4 and +0.80 ± 0.98 at T5. Both patients carrying mutations involving intragenic SHOX region (group A) and ones with regulatory region defects (group B) experienced a similar beneficial therapeutic effect. The multiple regression analysis identified the age at the start of rhGH treatment (β -0.31, p = 0.030) and the GV during the first year of rhGH treatment (β 0.45, p = 0.008) as main independent predictor factors of height gain. During rhGH therapy, no adverse event of concern was reported. Conclusions: Our data confirm the efficacy and safety of rhGH therapy in SHOX-D children, regardless the wide variety of genotype.


2023 - Refinement of the diagnostic approach for the identification of children and adolescents affected by familial hypercholesterolemia: Evidence from the LIPIGEN study [Articolo su rivista]
Casula, M.; Gazzotti, M.; Capra, M. E.; Olmastroni, E.; Galimberti, F.; Catapano, A. L.; Pederiva, C.; Anesi, A.; Arca, M.; Auricchio, R.; Averna, M.; Baldera, D.; Banderali, G.; Beccuti, G.; Benso, A.; Berteotti, M.; Bertolini, S.; Bianconi, V.; Biasucci, G.; Biolo, G.; Bonanni, L.; Borghi, C.; Bossi, A. C.; Branchi, A.; Bruzzi, P.; Bucci, M.; Buonuomo, P. S.; Calabro, P.; Calandra, S.; Carubbi, F.; Cavallaro, R.; Cefalu, A. B.; Cesaro, A.; Cipollone, F.; Citroni, N.; Colombo, E.; Coppola, C.; D'Addato, S.; Dal Pino, B.; Dalla Nora, E.; De Corrado, G.; Del Ben, M.; Di Molfetta, S.; Di Taranto, M. D.; Fainelli, G.; Federici, M.; Ferri, C.; Fiorenza, A. M.; Formisano, E.; Fortunato, G.; Giaccari, A.; Giorgino, F.; Grigore, L.; Guardamagna, O.; Iannuzzi, A.; Iannuzzo, G.; Iughetti, L.; Lia, S.; Longo, S.; Lupi, A.; Mandraffino, G.; Marcucci, R.; Maroni, L.; Massini, G.; Mazza, E.; Melchioda, E.; Meregalli, G.; Minicocci, I.; Moffa, S.; Mombelli, G.; Muntoni, S.; Nascimbeni, F.; Negri, E. A.; Notargiacomo, S.; Panfili, F. M.; Parati, G.; Passaro, A.; Pavanello, C.; Pecchioli, V.; Pecchioli, L.; Pellegatta, F.; Perla, F. M.; Pipolo, A.; Piro, S.; Pirro, M.; Pisciotta, L.; Pujia, R.; Putotto, C.; Repetti, E.; Rinaldi, E.; Romandini, A.; Sani, E.; Sarnari, S.; Sarzani, R.; Sbrana, F.; Scicali, R.; Scuruchi, M.; Suppressa, P.; Tarugi, P.; Trenti, C.; Vinci, P.; Werba, J. P.; Zambon, S.; Zambon, A.; Zenti, M. G.
abstract

Background and aims: We aimed to describe the limitations of familiar hypercholesterolemia (FH) diagnosis in childhood based on the presence of the typical features of FH, such as physical sings of cholesterol accumulation and personal or family history of premature cardiovascular disease or hypercholesterolemia, comparing their prevalence in the adult and paediatric FH population, and to illustrate how additional information can lead to a more effective diagnosis of FH at a younger age. Methods: From the Italian LIPIGEN cohort, we selected 1188 (≥18 years) and 708 (<18 years) genetically-confirmed heterozygous FH, with no missing personal FH features. The prevalence of personal and familial FH features was compared between the two groups. For a sub-group of the paediatric cohort (N = 374), data about premature coronary heart disease (CHD) in second-degree family members were also included in the evaluation. Results: The lower prevalence of typical FH features in children/adolescents vs adults was confirmed: the prevalence of tendon xanthoma was 2.1% vs 13.1%, and arcus cornealis was present in 1.6% vs 11.2% of the cohorts, respectively. No children presented clinical history of premature CHD or cerebral/peripheral vascular disease compared to 8.8% and 5.6% of adults, respectively. The prevalence of premature CHD in first-degree relatives was significantly higher in adults compared to children/adolescents (38.9% vs 19.7%). In the sub-cohort analysis, a premature CHD event in parents was reported in 63 out of 374 subjects (16.8%), but the percentage increased to 54.0% extending the evaluation also to second-degree relatives. Conclusions: In children, the typical FH features are clearly less informative than in adults. A more thorough data collection, adding information about second-degree relatives, could improve the diagnosis of FH at younger age.


2023 - Telemedicine usefulness in the follow-up of young people with diabetes 1 diabetes 2-years after the spread of COVID-19 [Abstract in Rivista]
Predieri, B; Candia, F; Stefanelli, F; Vandelli, S; Lucaccioni, L; Bruzzi, P; Iughetti, L
abstract


2023 - The oral communications presented by the young doctors at the meeting. Parmapediatrics 2023 [Articolo su rivista]
Barchi, L.; Bassoli, I.; Greco, A.; Fastiggi, M.; Bonvicini, F.; Iughetti, L.; De Fanti, A.
abstract


2023 - The treatment of obesity in children and adolescents: consensus position statement of the Italian society of pediatric endocrinology and diabetology, Italian Society of Pediatrics and Italian Society of Pediatric Surgery [Articolo su rivista]
Maffeis, Claudio; Olivieri, Francesca; Valerio, Giuliana; Verduci, Elvira; Licenziati, Maria Rosaria; Calcaterra, Valeria; Pelizzo, Gloria; Salerno, Mariacarolina; Staiano, Annamaria; Bernasconi, Sergio; Buganza, Raffaele; Crinò, Antonino; Corciulo, Nicola; Corica, Domenico; Destro, Francesca; Di Bonito, Procolo; Di Pietro, Mario; Di Sessa, Anna; Desanctis, Luisa; Faienza, Maria Felicia; Filannino, Grazia; Fintini, Danilo; Fornari, Elena; Franceschi, Roberto; Franco, Francesca; Franzese, Adriana; Giusti, Lia Franca; Grugni, Graziano; Iafusco, Dario; Iughetti, Lorenzo; Lera, Riccardo; Limauro, Raffaele; Maguolo, Alice; Mancioppi, Valentina; Manco, Melania; Del Giudice, Emanuele Miraglia; Morandi, Anita; Moro, Beatrice; Mozzillo, Enza; Rabbone, Ivana; Peverelli, Paola; Predieri, Barbara; Purromuto, Salvo; Stagi, Stefano; Street, Maria Elisabeth; Tanas, Rita; Tornese, Gianluca; Umano, Giuseppina Rosaria; Wasniewska, Malgorzata
abstract

This Position Statement updates the different components of the therapy of obesity (lifestyle intervention, drugs, and surgery) in children and adolescents, previously reported in the consensus position statement on pediatric obesity of the Italian Society of Pediatric Endocrinology and Diabetology and the Italian Society of Pediatrics. Lifestyle intervention is the first step of treatment. In children older than 12 years, pharmacotherapy is the second step, and bariatric surgery is the third one, in selected cases. Novelties are available in the field of the medical treatment of obesity. In particular, new drugs demonstrated their efficacy and safety and have been approved in adolescents. Moreover, several randomized control trials with other drugs are in process and it is likely that some of them will become available in the future. The increase of the portfolio of treatment options for obesity in children and adolescents is promising for a more effective treatment of this disorder.


2022 - A comparative study on the incidence of type 1 diabetes mellitus between children of North African migrants and Italian children in Emilia-Romagna region, Italy [Articolo su rivista]
Maltoni, G.; Zioutas, M.; Mosticchio, M.; Iughetti, L.; Predieri, B.; Bruzzi, P.; Iovane, B.; Lazzeroni, P.; Graziani, V.; Suprani, T.; Monti, S.; Street, M. E.; Lasagni, A.; De Luca, F.; Libertucci, F.; Mainetti, B.; Riboni, S.; Sogno Valin, P.; Pession, A.; Zucchini, S.
abstract

In the last few decades, many studies have reported an increasing global incidence of type 1 diabetes. Studies on migrant populations have underlined the importance of both environmental and genetic factors. Aims: Evaluate the incidence of type 1 diabetes in North African vs Italian children aged 0–14 years from 1 January 2015, to 31st December 2018, in Emilia-Romagna region, Italy. Methods: Clinical and epidemiological data about childhood onset type 1 diabetes in Emilia Romagna region were retrospectively collected by the regional centers of pediatric diabetology and matched using 3 different data sources. Results: 365 new cases were diagnosed. Total cumulative incidence was 15.4/100,000/year. North African cases showed a cumulative incidence of 53.8/100,000/year, statistically significant compared to cumulative incidence of the Italian cases alone 13.1/100,000/year (p value < 0.001). The annual incidence did not differ in the 4 years for both groups. Conclusion: The incidence of type 1 diabetes in the pediatric age (0 14 years) was significantly higher in the North African population than in the Italian one, suggesting that a mix of genetic and environmental factors may have caused the increase in newly diagnosed cases.What is Known:• The incidence of type 1 diabetes largely varies worldwide.• Study on immigrants helped to better understand the interplay role between genetics and environment.What is New:• This is the first study focused on the incidence of children and adolescents of North African migrants in Italy.• The incidence of children and adolescents of North African migrants in Emilia Romagna region, Italy, seems to be higher than that reported in the host countries, and, above all, than that reported in highest-incidence countries in Europe and in the world.


2022 - Antibiotic Resistance in Paediatric Febrile Urinary Tract Infections [Articolo su rivista]
Esposito, S.; Biasucci, G.; Pasini, A.; Predieri, B.; Vergine, G.; Crisafi, A.; Malaventura, C.; Casadio, L.; Sella, M.; Pierantoni, L.; Gatti, C.; Paglialonga, L.; Sodini, C.; La Scola, C.; Bernardi, L.; Autore, G.; Canto, G. D.; Argentiero, A.; Cantatore, S.; Ceccoli, M.; De Fanti, A.; Suppiej, A.; Lanari, M.; Principi, N.; Pession, A.; Iughetti, L.
abstract

Febrile urinary tract infection (UTI) is currently considered the most frequent cause of serious bacterial illness in children in the first 2 years of life. UTI in paediatrics can irreversibly damage the renal parenchyma and lead to chronic renal insufficiency and related problems. To avoid this risk, an early effective antibiotic treatment is essential. Moreover, prompt treatment is mandatory to improve the clinical condition of the patient, prevent bacteraemia, and avoid the risk of bacterial localization in other body sites. However, antibiotic resistance for UTI-related bacterial pathogens continuously increases, making recommendations rapidly outdated and the definition of the best empiric antibiotic therapy more difficult. Variation in pathogen susceptibility to antibiotics is essential for the choice of an effective therapy. Moreover, proper identification of cases at increased risk of difficult-to-treat UTIs can reduce the risk of ineffective therapy. In this review, the problem of emerging antibiotic resistance among pathogens associated with the development of paediatric febrile UTIs and the best potential solutions to ensure the most effective therapy are discussed. Literature analysis showed that the emergence of antibiotic resistance is an unavoidable phenomenon closely correlated with the use of antibiotics themselves. To limit the emergence of resistance, every effort to reduce and rationalise antibiotic consumption must be made. An increased use of antibiotic stewardship can be greatly effective in this regard.


2022 - Autosomal recessive cutis laxa type IIIA: Report of a patient with severe phenotype and review of the literature [Articolo su rivista]
Lugli, Licia; Cavalleri, Francesca; Bertucci, Emma; Fischer-Zirnsak, Björn; Cinelli, Giulia; Trevisani, Viola; Rossi, Cecilia; Riva, Marika; Iughetti, Lorenzo; Berardi, Alberto
abstract

Autosomal recessive cutis laxa type IIIA is a very rare genetic condition, caused by pathogenic variants in ALDH18A1, encoding delta-1-pyrroline-5-carboxylate synthase (P5CS). This enzyme catalyzes the reduction of glutamic acid to delta1-pyrroline-5-carboxylate, playing a key role in the de novo biosynthesis of proline, ornithine, and arginine. Autosomal recessive cutis laxa type IIIA is characterized by abundant and wrinkled skin, skeletal anomalies, cataract or corneal clouding and neuro-developmental disorders of variable degree. We report on a patient with autosomal recessive cutis laxa type IIIA, due to a homozygous missense c.1273C > T; p. (Arg425Cys) pathogenic variant in ALDH18A1. The patient presented a severe phenotype with serious urological involvement, peculiar cerebro-vascular abnormalities and neurodevelopmental compromise. This description contributes to better characterize the phenotypic spectrum associated with ALDH18A1 pathogenic variants, confirming the systemic involvement as a typical feature of autosomal recessive cutis laxa type IIIA.


2022 - Auxological data and glycemic control in children and adolescents with type 1 diabetes 2-years after the COVID-19 pandemic [Abstract in Rivista]
Iughetti, L.; Candia, F.; Stefanelli, F.; Trevisani, V.; Bruzzi, P.; Predieri, B.
abstract

Introduction: Since the beginning of the coronavirus disease 2019, (COVID-19) pandemic concerns for consequences on auxological data and glycemic control in patients with type 1 diabetes (T1D) were raised. Objectives: To investigate the 2-years effects of the COVID-19 pandemic on body mass index (BMI) and glycemic control in children and adolescents with T1D. Methods: Data on type and number of annual visit, auxological parameters [height (Ht), weight, and waist circumference (W)], insulin total daily dose (TDD), glycemic control (HbA1c), and weekly physical activity were collected during the annual routine outpatient visit between Dec 2021–Feb 2022 (T2) and were compared with those during the same period in 2019–20 (T0; before lockdown) and in 2020–21 (T1). Results: A 83 children and adolescents with T1D [65% male; median age 14.3 years (range 6.3–18.5); T1D duration 7.09 years (range 2.9–16.3)] were enrolled. The annual number of outpatient visits decreased (4 vs. 3 vs. 3; Χ2 = 74.2; p < 0.0001), while frequency of patient using telemedicine increased (0 vs. 55.4 vs. 33.7%; Χ2 = 48.1; p < 0.0001). BMI z-score significantly changed between periods, remaining within normal range values (0.19 vs. 0.08 vs. 0.23 SDS; Χ2 = 15.9; p < 0.001). Height and WHt ratio were comparable. Physical activity was significantly different between periods (4 vs. 0 vs. 5 h/week; Χ2 = 128.4; p < 0.0001) as well as insulin TDD (0.84 vs. 0.92 vs. 0.92 IU/kg/day; Χ2 = 8.19; p = 0.017). Average of annual HbA1c values significantly improved (62.1 vs. 60.5 vs. 60.6 mmol/mol; X2 = 12.8; p = 0.002). Rate of secondary DKA remained comparable and no severe hypoglycemic event was recorder during follow-up. Conclusions: In our patients, BMI z-score was unchanged and glycemic control remained improved in the 2-years after COVID-19 pandemic spread. Our data may be possibly related to both the resuming of regular exercise and the increased use of sensor during T1 that allowed to continue with telemedicine visits in T2, adjusting patients' insulin TDD and avoiding acute complications.


2022 - Can Fraction of Inspired Oxygen Predict Extubation Failure in Preterm Infants? [Articolo su rivista]
Spaggiari, E.; Amato, M.; Ricca, O. A.; Zini, L. C.; Bianchedi, I.; Lugli, L.; Boncompagni, A.; Guidotti, I.; Rossi, C.; Bedetti, L.; Iughetti, L.; Berardi, A.
abstract

Background: Prolonged mechanical ventilation in preterm infants may cause complications. We aimed to analyze the variables affecting extubation outcomes in preterm infants at high risk of extubation failure. Methods: This was a single-center, observational, retrospective study. Extubation failure was defined as survival with the need for reintubation within 72 h. Successfully extubated neonates (group 1) were compared to those with failed extubation (group 2). Multivariate logistic regression analysis evaluated factors that predicted extubation outcomes. Results: Eighty infants with a birth weight under 1000 g and/or gestational age (GA) under 28 weeks were included. Extubation failure occurred in 29 (36.2%) and success in 51 (63.8%) neonates. Most failures (75.9%) occurred within 24 h. Pre-extubation inspired oxygen fraction (FiO2) of 27% had a sensitivity of 58.6% and specificity of 64.7% for extubation failure. Post-extubation FiO2 of 32% had a sensitivity of 65.5% and specificity of 62.8% for failure. Prolonged membrane rupture (PROM) and high GA were associated with extubation success in multivariate logistic regression analysis. Conclusions: High GA and PROM were associated with extubation success. Pre-and post-extubation FiO2 values were not significantly predictive of extubation failure. Further studies should evaluate if overall assessment, including ventilatory parameters and clinical factors, can predict extubation success in neonates.


2022 - Challenges in the growth and development of newborns with extra-uterine growth restriction [Articolo su rivista]
Lucaccioni, L.; Iughetti, L.; Berardi, A.; Predieri, B.
abstract

Introduction: Extra-uterine growth restriction (EUGR) is a condition caused by the failure of very preterm infants to reach their potential growth during the NICU hospital stay. Despite enormous improvements in nutritional support and strategies, the growth pattern of preterm infants is still far from the one expected. Areas covered: This review focuses on what EUGR is, highlighting controversial aspects of this topic. EUGR is still missing a univocal definition, and the international debate is also open on what is the best growth chart to use. Moreover, professionals in NICU may not be trained on how to perform anthropometric measurements, increasing the risk of over- or underestimation, especially for length assessment. EUGR has recently been described as one of the main comorbidities in NICU, influencing growth, metabolism, and neurodevelopment later in life. Expert opinion: There is still much to investigate about what the best growth pattern in the NICU should be. What is known so far is that the majority of preterm neonates develop EUGR, and this leads to several short- and long-term consequences. It is imperative that neonatologists and pediatric endocrinologists work together, to modulate growth in the NICU.


2022 - Chemical contaminants in breast milk: a brief critical overview [Articolo su rivista]
Bernasconi, Sergio; Street, Maria Elisabeth; Iughetti, Lorenzo; Predieri, Barbara
abstract

Breast milk is the reference food for the infant both for its content in nutrients, necessary for normal growth and development, and for the presence of biologically active substances that provide protection from infections and a lower susceptibility to several non-communicable diseases typical of adulthood. However, substances that the mother assimilates from the environment, and which can be potentially harmful, can be concentrated in breast milk. In fact, for a long time, breast milk has been considered a reliable biomarker of the environment. The huge increase in the production and use of chemicals that has occurred in recent decades with consequent wide dispersion in the soil, water and air makes it necessary to carefully evaluate the levels of contamination. Based on a synthetic review of current knowledge, it can be confirmed that breast milk is always the first choice. However, various aspects remain to be clarified based on more robust scientific data. This review aims to stimulate further research, managed by multi-disciplinary teams which, with the use of the most modern chemical analysis tools, determine the presence of exogenous chemicals in longitudinal studies during pregnancy and lactation, clarifying their metabolic fate and evaluating them in the 'scope of global exposure (exposome). To this end, the gaps present in the studies conducted so far are also highlighted to make future scientific approaches increasingly robust.


2022 - Clinical Outcome of Discordant Empirical Therapy and Risk Factors Associated to Treatment Failure in Children Hospitalized for Urinary Tract Infections [Articolo su rivista]
Autore, G.; Neglia, C.; Di Costanzo, M.; Ceccoli, M.; Vergine, G.; La Scola, C.; Malaventura, C.; Falcioni, A.; Iacono, A.; Crisafi, A.; Iughetti, L.; Conte, M. L.; Pierantoni, L.; Gatti, C.; Biasucci, G.; Esposito, S.; Argentiero, A.; Bernardi, L.; Dal Canto, G.; Cortina, I.; Capra, M. E.; Benincasa, C.; Addeo, A.; Saia, R. E.; Lelli, F.; Pession, A.; Pasini, A.; Baccelli, F.; Bruni, L.; Gallotta, G.; Corvaglia, A.; Lanari, M.; Suppiej, A.; Cafolla, C.; Boselli, F.; Valletta, E.; Venturoli, V.; Casadio, L.; Polenzani, I.; Marchetti, F.; De Fanti, A.
abstract

With the spread of antibiotic resistance in pediatric urinary tract infections (UTIs), more patients are likely to be started empirically on antibiotics to which pathogens are later found to be resistant (discordant therapy). However, in-vivo effectiveness may be different from in-vitro susceptibility. Aims of this study were to describe clinical outcomes of discordant empirical treatments in pediatric UTIs and to investigate risk factors associated to treatment failure. This observational, retrospective study was conducted on children hospitalized for febrile UTIs with positive urine culture and started on discordant empirical therapy. Failure rates of discordant treatments and associated risk factors were investigated. A total of 142/1600 (8.9%) patients were treated with inadequate empirical antibiotics. Clinical failure was observed in 67/142 (47.2%) patients, with no fatal events. Higher failure rates were observed for combinations of penicillin and beta-lactamase inhibitors (57.1%). Significant risk factors for failure of discordant treatment were history of recurrent UTIs (95% CI: 1.13–9.98, OR: 3.23, p < 0.05), recent use of antibiotics (95% CI: 1.46–21.82, OR: 5.02, p < 0.01), infections caused by Pseudomonas aeruginosa (95% CI: 1.85–62.10, OR: 7.30, p < 0.05), and empirical treatment with combinations of penicillin and beta-lactamase inhibitors (95% CI: 0.94–4.03, OR: 1.94, p = 0.05). This study showed that discordant empirical treatments may still be effective in more than half of pediatric UTIs. Clinical effectiveness varies between different discordant antibiotics in pediatric UTIs, and patients presenting risk factors for treatment failure may need a differentiated empirical approach.


2022 - Correspondence on “Disorder of sex development associated with a novel homozygous nonsense mutation in COG6 expands the phenotypic spectrum of COG6-CDG” [Articolo su rivista]
Lugli, L.; Pollazzon, M.; Bigoni, S.; Caraffi, S. G.; Ferlini, A.; Ferri, L.; Morrone, A.; Calabrese, O.; Iughetti, L.; Garavelli, L.; Berardi, A.
abstract


2022 - Depression and Catatonia Associated With Lansoprazole in an Adolescent With Phelan-McDermid Syndrome: A Case Report [Articolo su rivista]
Persico, A.; Ricciardello, A.; Alessandrini, S.; Viola, L.; Bergonzini, P.; Iughetti, L.; Pani, L.
abstract


2022 - Early-life exposure to phthalates in a population of infants from the north of Italy: characterization and time trends [Abstract in Rivista]
Lucaccioni, L; Righi, E; Trevisani, V; Passini, E; Palandri, L; Bruzzi, P; Predieri, B; Iughetti, L
abstract

Phthalates are ubiquitous environmental contaminants and endocrine-disrupting chemicals (EDCs). Nowadays, they are considered reproductive toxicants and in-utero exposure is well documented, although evidence of early life exposure is scarce, and needs to be described. Aim of this study is to assess phthalate exposure and its changes over the first months of life in a cohort of healthy full term infants and their mothers from a restricted area of the north of Italy.


2022 - Efficacy of telemedicine in patients with type 1 diabetes over the second year by the COVID-19 pandemic spread [Abstract in Rivista]
Predieri, B.; Stefanelli, F.; Candia, F.; Trevisani, V.; Bruzzi, P.; Iughetti, L.
abstract

Introduction: During the lockdown due to the coronavirus disease, 2019 (COVID-19) pandemic, in-person outpatient visits were not possible, so telemedicine was rapidly adopted because of its potential to strengthen self-management support outside health care settings in the follow-up of patients with type 1 diabetes (T1D). Objectives: To investigate effectiveness of telemedicine in the follow-up of patients with T1D over the second year by the COVID-19 pandemic spread. Methods: Annual number of outpatient and telemedicine visits, insulin therapy, and HbA1c levels were collected in patients who performed the annual routine outpatients visits between Dec 2021 and Feb 2022 (T2) and were compared with those of the previous year 2020–21 (T1). Results: A total of 83 children and adolescents with T1D (65% male; median age 14.3 years; T1D duration 7.09 years) were enrolled. At T2, 28 subjects (Group A; 67.8% male) had ≥1 telemedicine visit, while other patients (Group B; 63.6% male) had not telemedicine visit; number of telemedicine visits were comparable between groups at T1. Patients of Group A, compared to Group B ones, were younger (13.7 vs. 14.9 years; p = 0.040). Insulin TDD and weekly physical activity were comparable. Insulin pump users were 53.6% in Group A and 20% in Group B; CGM users were 96.4 and 61.8%, respectively. Average of annual HbA1c levels was lower in Group A respect to Group B at T1 (52.6 vs. 65.4 mmol/mol; P < 0.0001) and T2 (52.8 vs. 63.1 mmol/mol; P < 0.0001). HbA1c values were longitudinally unchanged in Group A, while improved in Group B (p = 0.015). Rate of HbA1 ≤ 53 mmol/mol was 53.5% in Group A during both period; in Group B it was 9.1% at T1 and 10.9% at T2. Conclusions: Our data suggest that telemedicine over the second year by COVID-19 pandemic was effective to maintain a good glycemic control. Despite follow-up still indicate a preference for in-person diabetes care, we should consider an individual approach for telemedicine use, mainly for subjects with a good glycemic control and diabetes technologies users.


2022 - EIF2B2 gene mutation causing early onset vanishing white matter disease: a case report [Articolo su rivista]
Filareto, I.; Cinelli, G.; Scalabrini, I.; Caramaschi, E.; Bergonzini, P.; Spezia, E.; Todeschini, A.; Iughetti, L.
abstract

Background: Leukoencephalopathy with vanishing white matter (VWM) is an autosomal recessive neurological disease. The physiopathology of disease is still little understood, but it seems to involve impairment in maturation of astrocytes; as a consequence white matter is more prone to cellular stress. Disease is caused by mutations in five genes encoding subunits of the translation initiation factor eIF2B. We know five different types of VWM syndrome classified based different ages of onset (prenatal, infantile, childhood, juvenile and adult onset). Case presentation: We report the case of a 4-month-old boy with early seizure onset, recurrent hypoglycemia and post mortem diagnosis of vanishing white matter disease (VMD). At the admission he presented suspected critical episodes, resolved after intravenous administration of benzodiazepines. The brain MRI showed total absence of myelination that suggested hypomyelination leukoencephalopathy. The whole exome sequencing (WES) revealed a variant of EIF2B2 gene (p. Val308Met) present in homozygosity. In this case report we also describe the clinical evolution of seizures, in fact the epileptic seizures had a polymorphic aspect, from several complex partial seizures secondarily generalized to status epilepticus. Conclusion: Infantile and early childhood onset forms are associated with chronic progressive neurological signs, with episodes of rapid neurological worsening, and poor prognosis, with death in few months or years. Clinical presentation of epilepsy is poorly documented and do not include detailed information about the type, time of onset and severity of seizures. No therapeutic strategies for VWM disease have been reported.


2022 - Endocrine Disrupting Chemicals' Effects in Children: What We Know and What We Need to Learn? [Articolo su rivista]
Predieri, Barbara; Iughetti, Lorenzo; Bernasconi, Sergio; Street, Maria Elisabeth
abstract

Thousands of natural or manufactured chemicals were defined as endocrine-disrupting chemicals (EDCs) because they can interfere with hormone activity and the endocrine system. We summarize and discuss what we know and what we still need to learn about EDCs' pathogenic mechanisms of action, as well as the effects of the most common EDCs on endocrine system health in childhood. The MEDLINE database (PubMed) was searched on 13 May 2022, filtering for EDCs, endocrine diseases, and children. EDCs are a group of compounds with high heterogeneity, but usually disrupt the endocrine system by mimicking or interfering with natural hormones or interfering with the body's hormonal balance through other mechanisms. Individual EDCs were studied in detail, while humans' "cocktail effect" is still unclear. In utero, early postnatal life, and/or pubertal development are highly susceptible periods to exposure. Human epidemiological studies suggest that EDCs affect prenatal growth, thyroid function, glucose metabolism, obesity, puberty, and fertility through several mechanisms. Further studies are needed to clarify which EDCs can mainly act on epigenetic processes. A better understanding of EDCs' effects on human health is crucial to developing future regulatory strategies to prevent exposure and ensure the health of children today, in future generations, and in the environment.


2022 - Enteroviral Infections in the First Three Months of Life [Articolo su rivista]
Sandoni, M.; Ciardo, L.; Tamburini, C.; Boncompagni, A.; Rossi, C.; Guidotti, I.; Garetti, E.; Lugli, L.; Iughetti, L.; Berardi, A.
abstract

Enteroviruses (EVs) are an important source of infection in the paediatric age, with most cases concerning the neonatal age and early infancy. Molecular epidemiology is crucial to understand the circulation of main serotypes in a specific area and period due to their extreme epidemiological variability. The diagnosis of EVs infection currently relies on the detection of EVs RNA in biological samples (usually cerebrospinal fluid and plasma, but also throat swabs and feces) through a poly-merase chain reaction assay. Although EVs infections usually have a benign course, they sometimes become life threatening, especially when symptoms develop in the first few days of life. Mortality is primarily associated with myocarditis, acute hepatitis, and multi-organ failure. Neurodevelopmental sequelae have been reported following severe infections with central nervous system involvement. Unfortunately, at present, the treatment of EVs infections is mainly supportive. The use of specific antiviral agents in severe neonatal infections has been reported in single cases or studies includ-ing few neonates. Therefore, further studies are needed to confirm the efficacy of these drugs in clinical practice.


2022 - Environmental Factors in Northern Italy and Sickle Cell Disease Acute Complications: A Multicentric Study [Articolo su rivista]
Guerzoni, M. E.; Marchesi, S.; Palazzi, G.; Lodi, M.; Pinelli, M.; Venturelli, D.; Bigi, E.; Quaglia, N.; Corti, P.; Serra, R.; Colombatti, R.; Sainati, L.; Masera, N.; Colombo, F.; Barone, A.; Iughetti, L.
abstract

Background: Environmental factors seem to influence clinical manifestations of sickle cell disease (SCD), but few studies have shown consistent findings. We conducted a retrospective multicentric observational study to investigate the influence of environmental parameters on hospitalization for vaso-occlusive crises (VOC) or acute chest syndrome (ACS) in children with SCD. Methods: Hospital admissions were correlated with daily meteorological and air-quality data obtained from Environmental Regional Agencies in the period 2011–2015. The effect of different parameters was assessed on the day preceding the crisis up to ten days before. Statistical analysis was performed using a quasi-likelihood Poisson regression in a generalized linear model. Results: The risk of hospitalization was increased for low maximum temperature, low minimum relative humidity, and low atmospheric pressure and weakly for mean wind speed. The diurnal temperature range and temperature difference between two consecutive days were determined to be important causes of hospitalization. For air quality parameters, we found a correlation only for high levels of ozone and for low values at the tail corresponding to the lowest concentration of this pollutant. Conclusions: Temperature, atmospheric pressure, humidity and ozone levels influence acute complications of SCD. Patients’ education and the knowledge of the modes of actions of these factors could reduce hospitalizations.


2022 - Expert Opinion on the Management of Growth Hormone Deficiency in Brain Tumor Survivors: Results From an Italian Survey [Articolo su rivista]
Di Iorgi, N.; Morana, G.; Cappa, M.; D'Incerti, L.; Garre, M. L.; Grossi, A.; Iughetti, L.; Matarazzo, P.; Parpagnoli, M.; Pozzobon, G.; Salerno, M.; Sardi, I.; Wasniewska, M. G.; Zucchini, S.; Rossi, A.; Maghnie, M.
abstract

Background: Growth hormone deficiency (GHD) is the first and most common endocrine complication in pediatric brain tumor survivors (BTS). GHD can occur due to the presence of the tumor itself, surgery, or cranial radiotherapy (CRT). Aims: This study aimed to evaluate management and adherence to current guidelines of the Italian centers engaged in the diagnosis and follow-up of GHD patients with BTS. Methods: A multidisciplinary scientific board of pediatric endocrinologists, oncologists and radiologists with neuroimaging expertise discussed and reviewed the main issues relating to the management of GHD in pediatric BTS and developed a survey. The survey included questions relating to organizational aspects, risk factors, diagnosis, definition of stable disease, and treatment. The online survey was sent to an expanded panel of specialists dedicated to the care of pediatric BTS, distributed among the three specialty areas and throughout the country (23 Italian cities and 37 Centers). Results: The online questionnaire was completed by 86.5% (32 out of 37) of the Centers involved. Most had experience in treating these patients, reporting that they follow more than 50 BTS patients per year. Responses were analyzed descriptively and aggregated by physician specialty. Overall, the results of the survey showed some important controversies in real life adherence to the current guidelines, with discrepancies between endocrinologists and oncologists in the definition of risk factors, diagnostic work-up, decision-making processes and safety. Furthermore, there was no agreement on the neuroimaging definition of stable oncological disease and how to manage growth hormone therapy in patients with residual tumor and GHD. Conclusions: The results of the first Italian national survey on the management of GHD in BTS highlighted the difference in management on some important issues. The time to start and stop rhGH treatment represent areas of major uncertainty. The definition of stable disease remains critical and represents a gap in knowledge that must be addressed within the international guidelines in order to increase height and to improve metabolic and quality of life outcomes in cancer survivors with GHD.


2022 - Gut-dependent inflammation and alterations of the intestinal microbiota in individuals with perinatal HIV exposure and different HIV serostatus [Articolo su rivista]
Tincati, C.; Ficara, M.; Ferrari, F.; Augello, M.; Dotta, L.; Tagliabue, C.; Diana, A.; Camelli, V.; Iughetti, L.; Badolato, R.; Cellini, M.; Marchetti, G.
abstract

Objective: HIV-exposed infected (HEI) and uninfected (HEU) children represent the two possible outcomes of maternal HIV infection. Modifications of the intestinal microbiome have been linked to clinical vulnerability in both settings, yet whether HEI and HEU differ in terms of gut impairment and peripheral inflammation/activation is unknown. Design: We performed a cross-sectional, pilot study on fecal and plasma microbiome as well as plasma markers of gut damage, microbial translocation, inflammation and immune activation in HIV-infected and uninfected children born from an HIV-infected mother. Methods: Fecal and plasma microbiome were determined by means of 16S rDNA amplification with subsequent qPCR quantification. Plasma markers were quantified via ELISA. Results: Forty-seven HEI and 33 HEU children were consecutively enrolled. The two groups displayed differences in fecal beta-diversity and relative abundance, yet similar microbiome profiles in plasma as well as comparable gut damage and microbial translocation. In contrast, monocyte activation (sCD14) and systemic inflammation (IL-6) were significantly higher in HEI than HEU. Conclusion: In the setting of perinatal HIV infection, enduring immune activation and inflammation do not appear to be linked to alterations within the gut. Given that markers of activation and inflammation are independent predictors of HIV disease progression, future studies are needed to understand the underlying mechanisms of such processes and elaborate adjuvant therapies to reduce the clinical risk in individuals with perinatal HIV infection.


2022 - Isolated childhood growth hormone deficiency: a 30-year experience on final height and a new prediction model [Articolo su rivista]
Lonero, A.; Giotta, M.; Guerrini, G.; Calcaterra, V.; Galazzi, E.; Iughetti, L.; Cassio, A.; Wasniewska, G. M.; Mameli, C.; Tornese, G.; Salerno, M.; Cherubini, V.; Caruso Nicoletti, M.; Street, M. E.; Grandone, A.; Giacomozzi, C.; Faienza, M. F.; Guzzetti, C.; Bellone, S.; Parpagnoli, M.; Musolino, G.; Maggio, M. C.; Bozzola, M.; Trerotoli, P.; Del vecchio, M.
abstract

Purpose: We aimed to evaluate the near-final height (nFHt) in a large cohort of pediatricpatients with growth hormone deficiency (GHD) and to elaborate a new predictive method of nFHt. Methods: We recruited GHD patients diagnosed between 1987 and 2014 and followed-up until nFHt. To predict the values of nFHt, each predictor was run in a univariable spline. Results: We enrolled 1051 patients. Pre-treatment height was −2.43 SDS, lower than parental height (THt) (−1.09 SDS, p < 0.001). The dose of recombinant human GH (rhGH) was 0.21mg/kg/week at start of treatment. nFHt was −1.08 SDS (height gain 1.27 SDS), higher than pre-treatment height (p < 0.001) and comparable to THt. 1.6% of the patients were shorter than −2 SDS from THt. The rhGH dose at nFHt was 0.19 mg/kg/week, lower than at the start (p < 0.001). The polynomial regression showed that nFHt was affected by gender, THt, age at puberty, height at puberty, age at the end of treatment (F = 325.37, p < 0.0001, R2 87.2%). Conclusion: This large national study shows that GHD children can reach their THt. The rhGH/kg/day dose significantly decreased from the start to the end of the treatment. Our model suggests the importance of a timely diagnosis, possibly before puberty, the beneficial effect of long-term treatment with rhGH, and the key-role of THt. Our prediction model has a very acceptable error compared to the majority of other published studies.


2022 - La disforia di genere in età pediatrica e adolescenziale: nozioni per il pediatra [Articolo su rivista]
Ciancia, S; Iughetti, L
abstract

The number of children and adolescents referred to the gender identity clinics is significantly increasing. The pediatrician often represents the first healthcare professional to be consulted by families or who suspects a gender identity disorder. Consequently, the knowledge of some notions related to this condition are essential to provide the basic care to the child/adolescent and address the topic in the most appropriate manner. Thereafter, the care will require a multidisciplinary team composed of professionals who received a specific education.


2022 - Linfoadenopatia: quando non la sai pensa alla ROSAI... [Abstract in Rivista]
Scarponi, D; Caccamo, P; Bondi, C; D’Agosto, A; Facchini, L; Zavaglio, C; Montanari, F; Predieri, B; Iughetti, L
abstract


2022 - Management of Childhood-onset Craniopharyngioma in Italy: A Multicenter, 7-Year Follow-up Study of 145 Patients [Articolo su rivista]
Zucchini, S.; Di Iorgi, N.; Pozzobon, G.; Pedicelli, S.; Parpagnoli, M.; Driul, D.; Matarazzo, P.; Baronio, F.; Crocco, M.; Iudica, G.; Partenope, C.; Nardini, B.; Ubertini, G.; Menardi, R.; Guzzetti, C.; Iughetti, L.; Aversa, T.; Di Mase, R.; Cassio, A.; Cianfarani, S.; Maghnie, M.; Tuli, G.; Loche, S.; Bruzzi, P.; Wasniewska, M.; Salerno, M.; Rutigliano, I.; Iezzi, M. L.; Cherubini, V.; Grandone, A.; Faienza, M. F.; Tumini, S.; Baldoli, C.; Consales, A.; Genitori, L.; Marras, C. E.; Milanaccio, C.; Mortini, P.; Vindigni, M.; Zenga, F.; Zucchelli, M.
abstract

Context: Nationwide data on children diagnosed with craniopharyngioma (CP) are not available in Italy. Objective: This work aimed to identify patients' characteristics, type of surgical approach, complications and recurrences, number of pituitary deficits, and number of patients starting growth hormone (GH) treatment. Methods: A retrospective multicenter collection took place of 145 patients aged 0 to 18 years who underwent surgery for CP between 2000 and 2018, and followed up in 17 Italian centers of pediatric endocrinology. Results: Age at diagnosis was 8.4 ± 4.1 years. Duration of symptoms was 10.8 ± 12.5 months and headache was most frequent (54%), followed by impaired growth (48%) and visual disturbances (44%). Most lesions were suprasellar (85%), and histology was adamantinomatous in all cases but two. Surgical approach was transcranial (TC) in 67.5% of cases and transsphenoidal (TS) in 31.%. The TC approach was prevalent in all age groups. Postsurgery complications occurred in 53% of cases, with water-electrolyte disturbances most frequent. Radiotherapy was used in 39% of cases. All patients but one presented with at least one hormone pituitary deficiency, with thyrotropin deficiency most frequent (98.3%), followed by adrenocorticotropin (96.8%), arginine vasopressin (91.1%), and GH (77.4%). Body mass index (BMI) significantly increased over time. A hypothalamic disturbance was present in 55% of cases. GH therapy was started during follow-up in 112 patients at a mean age of 10.6 years, and 54 developed a recurrence or regrowth of the residual lesion. Conclusion: CP is often diagnosed late in Italy, with TC more frequent than the TS surgical approach. Postsurgery complications were not rare, and hypopituitarism developed almost in all cases. BMI shows a tendency to increase overtime.


2022 - Management of Pediatric Urinary Tract Infections: A Delphi Study [Articolo su rivista]
Autore, G.; Bernardi, L.; La Scola, C.; Ghidini, F.; Marchetti, F.; Pasini, A.; Pierantoni, L.; Castellini, C.; Gatti, C.; Malaventura, C.; Pelusi, G.; Antodaro, F.; Bergomi, A.; Mazzini, F.; Parente, G.; Pillon, R.; Cusenza, F.; Biasucci, G.; De Fanti, A.; Iughetti, L.; Perrone, S.; Pession, A.; Lima, M.; Esposito, S.
abstract

Urinary tract infection (UTI) is one of the most common infectious diseases in the pediatric population and represents a major cause of antibiotic consumption and hospitalization in children. Considering the ongoing controversies on the management of pediatric UTI and the challenges due to increasing antimicrobial resistance, the aim of the present study was to evaluate the level of agreement on UTI management in pediatric age in Emilia-Romagna Region, Italy, and to assess on the basis of recent studies whether there is the need to change current recommendations used by primary care pediatricians, hospital pediatricians, and pediatric surgeons in everyday clinical practice to possibly improve outcomes. This consensus provides clear and shared indications on UTI management in pediatric age, based on the most updated literature. This work represents, in our opinion, the most complete and up-to-date collection of statements on procedures to follow for pediatric UTI, in order to guide physicians in the management of the patient, standardize approaches, and avoid abuse and misuse of antibiotics. Undoubtedly, more randomized and controlled trials are needed in the pediatric population to better define the best therapeutic management in cases with antimicrobial resistance and real usefulness of long-term antibiotic prophylaxis.


2022 - Multiple thrombosis of the cerebral venous sinuses, neonatal seizures, and minor parenchymal lesions: a case report and a review of the literature [Articolo su rivista]
Bedetti, L.; Poluzzi, S.; Guidotti, I.; Lucaccioni, L.; Rota, C.; Cavalleri, F.; Pugliese, M.; Iughetti, L.; Lugli, L.; Berardi, A.
abstract

Background: Cerebral sinovenous thrombosis (CSVT) is a rare disease with potential catastrophic consequences. However, neonatal brain damage after venous injury and long-term neurologic outcomes have been poorly investigated. Some found an association between site and number of sinus occlusions, severity of lesions, clinical presentation and the neurodevelopmental outcome. Case presentation: We describe the case of a term newborn girl with multiple CSVT who presented with clonic seizures and who received early treatment with heparin. MRI scans showed a progressive recanalization of deep venous system, and only minor cerebral lesions were present at 3 months of life. Neurocognitive outcome was normal at 12 months of life. Conclusions: This case demonstrates that multiple CSVT presenting with severe seizures does not necessarily underlie major cerebral lesions or lead to severely abnormal neurodevelopmental outcome.


2022 - Neonatal septic shock, a focus on first line interventions [Articolo su rivista]
Spaggiari, Valentina; Passini, Erica; Crestani, Sara; Roversi, Maria Federica; Bedetti, Luca; Rossi, Katia; Lucaccioni, Laura; Baraldi, Cecilia; Della Casa Muttini, Elisa; Lugli, Licia; Iughetti, Lorenzo; Berardi, Alberto
abstract

Septic shock is a main cause of morbidity and mortality in neonates. Septic shock evolves from compensated to uncompensated through 3 distinct phases. Prompt diagnosis is challenging, since neonatal septic shock may overlap with the physiological changes occurring at birth. The outcome of septic shock depends on a prompt recognition of symptoms and a strict adherence to cardiopulmonary resuscitation guidelines. Fluid administration plays a major role in the initial management of septic shock. If there is no response to volume filling, inotropes must be infused within one hour of onset (dopamine, dobutamine, adrenaline). Life-threatening infections require immediate and aggressive empiric use of antimicrobials. In the pediatric age, delay in antibiotic initiation for treating septic shock is associated with poor outcome and increased risk of mortality. There is a gap regarding first line interventions in neonatal septic shock. This review addresses initial interventions in the treatment of neonatal septic shock and discusses currently available evidences., These interventions may allow to improve the outcome if they are promptly carried out.


2022 - New insights on the effects of endocrine-disrupting chemicals on children [Articolo su rivista]
Predieri, B.; Alves, C. A. D.; Iughetti, L.
abstract

Objective: Endocrine disrupting chemicals (EDCs) are present in many areas and materials of the common life, and exposure to these chemicals can occur from products to personal care, from air and food. This review aims to summarize the more recent epidemiological findings for the impact of EDCs on endocrine system health in children, including effects in growth, metabolism, sexual development, and reproduction. Sources: The MEDLINE database (PubMed) was searched on August 24th, 2021, filtering for EDCs, endocrine disruptors, children, and humans. Summary of the findings: Intrauterine exposure of EDCs can have transgenerational effects, thus laying the foundation for disease in later life. The dose-response relationship may not always be predictable as even low-level exposures that may occur in everyday life can have significant effects on a susceptible individual. Although individual compounds have been studied in detail, the effects of a combination of these chemicals are yet to be studied to understand the real-life situation where human beings are exposed to a “cocktail effect” of these EDCs. Epidemiological studies in humans suggest EDCs’ effects on prenatal growth, thyroid function, glucose metabolism, obesity, puberty, and fertility mainly through epigenetic mechanisms. Conclusions: EDCs cause adverse effects in animals, and their effects on human health are now known and irrefutable. Because people are typically exposed to multiple endocrine disruptors, assessing public health effects is difficult. Legislation to ban EDCs and protect especially pregnant women and young children is required and needs to be revised and adjusted to new developments on a regular basis.


2022 - Omenn Syndrome due to RAG1 Mutation Presenting With Nonimmune Hydrops Fetalis in Two Siblings [Articolo su rivista]
Valeri, L.; Lugli, L.; Iughetti, L.; Soresina, A.; Giliani, S.; Porta, F.; Berardi, A.
abstract

Omenn syndrome (OS) is a rare variant of severe combined immunodeficiency characterized by susceptibility to severe opportunistic infections and peculiar manifestations, such as protein-losing erythroderma, alopecia, hepatosplenomegaly, lymphadenopathies, and severe diarrhea. The typical form of the disease is caused by hypomorphic mutation of the recombination-activating genes (RAG1 and RAG2), which are critical in initiating the molecular processes leading to lymphocyte and immunoglobulin receptor formation. Affected patients lack B cells, whereas autoreactive oligoclonal T cells infiltrate the skin, gut, spleen, and liver. In the absence of hematopoietic stem cell transplantation, patients with OS usually succumb early in life because of opportunistic infections. The incidence of OS is estimated to be <1 per 1 000 000; however, the actual frequency is difficult to ascertain. We report 2 siblings affected by OS due to a homozygous frameshift mutation (NM_000448.3:c.519delT, p.E174Sfs*26) in the RAG1 gene presenting with nonimmune hydrops fetalis (NIHF). To the best of our knowledge, this is the first reported association between OS and NIHF. NIHF specifically refers to the presence of ≥2 abnormal fluid collections in the fetus, without red blood cell alloimmunization. A broad spectrum of pathologies is associated with NIHF; however, in ∼20% of the cases, the primary cause remains unclear. Understanding the etiology of NIHF is essential for guiding clinical management, determining prognosis, and informing parents regarding recurrence risk. Our case contributes to expanding the spectrum of OS presentation and highlights the importance of a complete immunologic and genetic workup in otherwise unexplained cases of NIHF.


2022 - Polygraphic EEG Can Identify Asphyxiated Infants for Therapeutic Hypothermia and Predict Neurodevelopmental Outcomes [Articolo su rivista]
Lugli, L.; Guidotti, I.; Pugliese, M.; Roversi, M. F.; Bedetti, L.; Della Casa Muttini, E.; Cavalleri, F.; Todeschini, A.; Genovese, M.; Ori, L.; Amato, M.; Miselli, F.; Lucaccioni, L.; Bertoncelli, N.; Candia, F.; Maura, T.; Iughetti, L.; Ferrari, F.; Berardi, A.
abstract

Background: Neonatal encephalopathy due to perinatal asphyxia is one of the leading causes of neonatal death and morbidity worldwide. The neurodevelopmental outcomes of asphyxiated neonates have considerably improved after therapeutic hypothermia (TH). The current challenge is to identify all newborns with encephalopathy at risk of cerebral lesions and subsequent disability within 6 h of life and who may be within the window period for treatment with TH. This study evaluated the neurodevelopmental outcomes in surviving asphyxiated neonates who did and did not receive TH, based on clinical and polygraphic electroencephalographic (p-EEG) criteria. Methods: The study included 139 asphyxiated newborns divided into two groups: 82 who received TH and 57 who were not cooled. TH was administered to asphyxiated newborns (gestational age ≥ 35 weeks, birth weight ≥ 1800 g) with encephalopathy of any grade and moderate-to-severe p-EEG abnormalities or seizures. Neurodevelopmental outcomes between the groups at 24 months of life and the risk factors for severe outcomes were assessed. Results: Severe neurodevelopmental impairment occurred in 10 (7.2%) out of the 139 enrolled neonates. Nine out of the 82 cooled neonates (11.0%) had severe neurodevelopmental impairment. All but one neonate (98.2%) who did not receive TH had normal outcomes. The multivariate logistic regression analysis showed that abnormal p-EEG patterns (OR: 27.6; IC: 2.8–267.6) and general movements (OR: 3.2; IC: 1.0–10.0) were significantly associated with severe neurodevelopmental impairment (area under ROC curve: 92.7%). Conclusion: The combination of clinical and p-EEG evaluations in hypoxic–ischemic encephalopathy contributed to a more accurate selection of patients treated with therapeutic hypothermia. When administered to infants with moderate to severe p-EEG abnormalities, TH prevents approximately 90% of severe neurodevelopmental impairment after any grade of hypoxic–ischemic encephalopathy.


2022 - Should we give antibiotics to neonates with mild non-progressive symptoms? A comparison of serial clinical observation and the neonatal sepsis risk calculator [Articolo su rivista]
Berardi, A.; Zinani, I.; Bedetti, L.; Vaccina, E.; Toschi, A.; Toni, G.; Lecis, M.; Leone, F.; Monari, F.; Cozzolino, M.; Zini, T.; Boncompagni, A.; Iughetti, L.; Miselli, F.; Lugli, L.
abstract


2022 - Specific miRNAs Change After 3 Months of GH treatment and Contribute to Explain the Growth Response After 12 Months [Articolo su rivista]
Catellani, Cecilia; Ravegnini, Gloria; Sartori, Chiara; Righi, Beatrice; Lazzeroni, Pietro; Bonvicini, Laura; Poluzzi, Silvia; Cirillo, Francesca; Predieri, Barbara; Iughetti, Lorenzo; Giorgi Rossi, Paolo; Angelini, Sabrina; Street, Maria Elisabeth
abstract

Context: There is growing evidence of the role of epigenetic regulation of growth, and miRNAs potentially play a role. Objective: The aim of this study is to identify changes in circulating miRNAs following GH treatment in subjects with isolated idiopathic GH deficiency (IIGHD) after the first 3 months of treatment, and verify whether these early changes can predict growth response. Design and methods: The expression profiles of 384 miRNAs were analyzed in serum in 10 prepubertal patients with IIGHD (5 M, 5 F) at two time points before starting GH treatment (t-3, t0), and at 3 months on treatment (t+3). MiRNAs with a fold change (FC) >+1.5 or <-1.5 at t+3 were considered as differentially expressed. In silico analysis of target genes and pathways led to a validation step on 8 miRNAs in 25 patients. Clinical and biochemical parameters were collected at baseline, and at 6 and 12 months. Simple linear regression analysis and multiple stepwise linear regression models were used to explain the growth response. Results: Sixteen miRNAs were upregulated and 2 were downregulated at t+3 months. MiR-199a-5p (p = 0.020), miR-335-5p (p = 0.001), and miR-494-3p (p = 0.026) were confirmed to be upregulated at t+3. Changes were independent of GH peak values at testing, and levels stabilized after 12 months. The predicted growth response at 12 months was considerably improved compared with models using the common clinical and biochemical parameters. Conclusions: MiR-199a-5p, miR-335-5p, and miR-494-3p changed after 3 months of GH treatment and likely reflected both the degree of GH deficiency and the sensitivity to treatment. Furthermore, they were of considerable importance to predict growth response.


2022 - SUBOPTIMAL ADHERENCE TO STATIN THERAPY IN CHILDREN AND ADOLESCENTS WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA DESPITE A HIGH THERAPEUTIC EFFICACY: IS THE CARDIOVASCULAR RISK UNDERESTIMATED? [Abstract in Rivista]
Bruzzi, P.; Di Martino, M.; Di Caprio, A.; Trevisani, V.; Cattini, U.; Madeo, S. F.; Lucaccioni, L.; Predieri, B.; Iughetti, L.
abstract

Background. European guidelines currently support the initiation of statin by age 8-10 years in patients with heterozygous familial hypercholesterolemia (HeFH) to slow the progression of endothelial disfunction and to reduce the risk of cardiovascular disease in adulthood. However, to date, there is lack of data on adherence to statins in the paediatric population. Therefore, we describe our real-life paediatric experience about efficacy and adherence of statin therapy. Methods. This is a monocentric, observational study recruiting children and adolescents with genetically confirmed HeFH. Anthropometric measures, fasting lipid profile and therapeutic data were collected at diagnosis of HeFH [T0], on lipid-lowering diet [T1], four weeks after starting statin therapy [T2] and yearly during the first two years on statin [T3 and T4]. Results. 24 HeFH children and adolescents (17/24 female) were started on statin at a mean age of 13.77±3.09 years (12 on atorvastatin, 10 on pravastatin and 2 on simvastatin). On lipid-lowering diet, lipid metabolism did not change significantly [LDL-C 237.61±47.18 vs. 218.22±50.15 mg/dl, p 0.11], while on statin the improvement was quick and persistent [LDL-C T1 218.22±50.15, T2 163.85±27.64, T3 153.12±34.90, T4 156.37±34.11 mg/dl, p<0.05]. The mean reduction of LDL-C in comparison to baseline levels was: -34.68±12.99% at T2 and -30.42±20.78% at T4. Despite this efficacy and excluding one case of statin-intolerance, 9/23 patients (about 39%) dropped out after one year of statin therapy with a higher prevalence among families without an history of precocious cardio-vascular events (p <0.05). Conclusions. We report an overall scarce adherence to statins in our paediatric HeFH population despite an efficacy in line with international data. GP involvement, a more effective communication with patients and their families to emphasize the high HeFH-related cardiovascular risk, and a periodic follow-up including telemedicine may be tools to achieve a better adherence.


2022 - The Hyperphagia Questionnaire: Insights From a Multicentric Validation Study in Individuals With Prader Willi Syndrome [Articolo su rivista]
Licenziati, M. R.; Bacchini, D.; Crino, A.; Grugni, G.; Fintini, D.; Osimani, S.; Ragusa, L.; Sacco, M.; Iughetti, L.; De Sanctis, L.; Franzese, A.; Wasniewska, M. G.; Faienza, M. F.; Delvecchio, M.; Esposito, C.; Valerio, G.
abstract

Background/Objectives: The present study aimed to validate the Italian version of the Hyperphagia Questionnaire (HQ), a 11-items questionnaire developed to assess hyperphagia in individuals with Prader-Willi syndrome (PWS). This is a complex neurodevelopmental disorder characterized by endocrine dysfunction, hypotonia, intellectual disability, psychiatric disorders and obesity. Methods: Parents of 219 individuals with PWS (age range 3–54 years; Mage = 17.90; 108 Males), recruited in 12 hospitals in Italy responded to HQ during routine visits. In function of the level of analyses the sample was divided into two subgroups (<18> years) or into four age-subgroups (2.5–4.5; 4.5–8; 8–18; >18 years) corresponding to different clinical stages. Results: Confirmatory factor analysis (CFA) confirmed the three hyperphagic subdimensions of the original structure (behavior, drive, and severity), but one item was dropped out, reducing the final version to 10 items. Using multi-group CFA, HQ showed satisfactory indexes of measurement invariance by age. Good indexes of internal consistency (Cronbach's alpha and McDonald's Omega coefficients) were found for each subdimension. The three hyperphagia subdimensions positively converged with other food-related measures: emotional overeating, food enjoyment, food responsiveness, and satiety responsiveness. A significant increase of all hyperphagic subdimensions was found across age groups. Higher hyperphagic levels were found in participants with higher body mass index. Hyperphagic drive differently increased in function of the interaction between age and underlying genetic mechanisms. Conclusion: The Italian version of the HQ is a psychometrically valid and reliable instrument for assessing hyperphagia in individuals with PWS. This tool may prove useful to evaluate the efficacy of pharmacologic and rehabilitative treatments.


2022 - The impact of BMI on long-term anthropometric and metabolic outcomes in girls with idiopathic central precocious puberty treated with GnRHas [Articolo su rivista]
Bruzzi, Patrizia; Valeri, Lara; Sandoni, Marcello; Madeo, Simona Filomena; Predieri, Barbara; Lucaccioni, Laura; Iughetti, Lorenzo
abstract

BackgroundGonadotropin-releasing hormone analogs (GnRHas) are effective in increasing the final height of children with idiopathic central precocious puberty (ICPP). However, in previous years, some transient metabolic complications have been described during this treatment, for which there are no long-term outcome data. Our study aimed to evaluate the efficacy of GnRHas and clarify if body mass index (BMI) at diagnosis of ICPP could influence long-term outcomes. MethodsThis was an observational, retrospective study that recruited a cohort of girls with ICPP. Data for anthropometric measures, fasting lipid profile, and glucose metabolism were collected at baseline [when GnRHas treatment started (T1)], at the end of the treatment (T2), and near-final height (nFH) or final height (FH) (T3). Predicted adult height (PAH) was calculated at T1 following Bayley and Pinneau's method. Analysis was carried out using BMI standard deviation score (SDS) categories at T1 (group A, normal weight, vs. group B, overweight/obese). ResultsFifty-seven girls with ICPP who were treated with GnRHas were enrolled in the study (group A vs. group B: 33 vs. 24 patients, aged 7.86 +/- 0.81 vs. 7.06 +/- 1.61 years, respectively; p < 0.05). In the study population, nFH/FH was in line with the target height (TH) (p = 0.54), with a mean absolute height gain of 11.82 +/- 5.35 cm compared with PAH. Even if the length of therapy was shorter (group A vs. group B: 1.84 +/- 2.15 vs. 2.10 +/- 0.81 years, respectively; p < 0.05) and the age at menarche was younger (group A vs. group B: 10.56 +/- 1.01 vs. 11.44 +/- 0.85 years, respectively; p < 0.05) in group B than in group A, the nFH/FH gain was still comparable between the two groups (p = 0.95). At nFH/FH, BMI SDS was still greater in group B than in group A (p = 0.012), despite the fact that BMI SDS significantly increased in group A only (p < 0.05). Glucose metabolism got worst during GnRHa with a complete restoring after it, independently from pre-treatment BMI. The ratio of low-density to high-density lipoprotein cholesterol transiently deteriorated during treatment with GnRHas in group A only (p = 0.030). ConclusionsOur results confirm the effectiveness of treatment with GnRHas on growth and do not support the concern that being overweight and obese can impair the long-term outcomes of GnRHas therapy. However, the observed transient impairment of metabolic parameters during treatment suggests that clinicians should encourage ICPP girls treated with GnRHas to have a healthy lifestyle, regardless of their pretreatment BMI.


2022 - The Role of Registers in Increasing Knowledge and Improving Management of Children and Adolescents Affected by Familial Hypercholesterolemia: the LIPIGEN Pediatric Group [Articolo su rivista]
Gazzotti, Marta; Casula, Manuela; Bertolini, Stefano; Capra, Maria Elena; Olmastroni, Elena; Catapano, Alberico Luigi; Pederiva, Cristina; Iughetti, L
abstract

Pathology registers can be a useful tool to overcome obstacles in the identification and management of familial hypercholesterolemia since childhood. In 2018, the LIPIGEN pediatric group was constituted within the Italian LIPIGEN study to focus on FH subjects under 18 years. This work aimed at discussing its recent progress and early outcomes. Demographic, biochemical, and genetic baseline characteristics were collected, with an in-depth analysis of the genetic defects. The analysis was carried out on 1,602 children and adolescents (mean age at baseline 9.9 +/- 4.0 years), and almost the whole cohort underwent the genetic test (93.3%). Overall, the untreated mean value of LDL-C was 220.0 +/- 97.2 mg/dl, with an increasing gradient from subjects with a negative (N = 317; mean untreated LDL-C = 159.9 +/- 47.7 mg/dl), inconclusive (N = 125; mean untreated LDL-C = 166.4 +/- 56.5 mg/dl), or positive (N = 1,053; mean untreated LDL-C = 246.5 +/- 102.1 mg/dl) genetic diagnosis of FH. In the latter group, the LDL-C values presented a great variability based on the number and the biological impact of involved causative variants. The LIPIGEN pediatric group represents one of the largest cohorts of children with FH, allowing the deepening of the characterization of their baseline and genetic features, providing the basis for further longitudinal investigations for complete details.


2022 - Townes-Brocks syndrome with craniosynostosis in two siblings [Articolo su rivista]
Lugli, L.; Rossi, C.; Ceccarelli, P. L.; Calabrese, O.; Bedetti, L.; Miselli, F.; Bianchini, M. A.; Iughetti, L.; Berardi, A.
abstract

This report describes a novel truncating c.709C > T p.(Gln237*) SALL1 variant in two siblings exhibiting sagittal craniosynostosis as a unique feature of Townes-Brocks syndrome (TBS, OMIM #107480). TBS is a rare autosomal dominant syndrome with variable phenotypes, including anorectal, renal, limb, and ear abnormalities, which results from heterozygous variants in the SALL1 gene, predominantly located in the 802 bp “hot spot region” within exon 2. Recent studies have suggested that aberrations in primary cilia and sonic hedgehog signalling contribute to the TBS phenotypes. The presence of the novel c.709C > T p.(Gln237*) SALL1 variant was confirmed in both the siblings and their father, whereas no mutations currently associated with craniosynostosis were detected. We hypothesise that the truncating c.709C > T p.(Gln237*) SALL1 variant, which occurs outside the “hot spot region” and inside the glutamine-rich domain coding region, could interfere with ciliary signalling and mechanotransduction, contributing to premature fusion of calvarial sutures. This report broadens the genetic and phenotypic spectrum of TBS and provides the first clinical evidence of craniosynostosis as a novel feature of the syndrome.


2022 - Use of urinary gonadotropins for the evaluation of the minipubertal profile in term newborns and infants within the first six months of age [Abstract in Rivista]
Lucaccioni, L; Trevisani, V; Passini, E; Palandri, L; Bruzzi, P; Predieri, B; Righi, E; Iughetti, L
abstract

The activation of the hypothalamus-pituitarygonadal (HPG) axis during the first months both in males(M) and females(F) is named as minipuberty. Urinary gonadotropins (uGn) represent an unexpensive and non-invasive method of assessing pubertal development and they have recently been used also for studying minipuberty. Aims of this study are: 1) to describe the urinary hormonal pattern (uLH, uFSH, testosterone – uT, oestradiol-uE) during minipuberty in a group of healthy full-term infants. 2) to identify the relationship between urinary hormone levels and environmental factors, anthropometric measurements, anogenital distances (AGD).


2021 - Antibiotic use in very low birth weight neonates after an antimicrobial stewardship program [Articolo su rivista]
Berardi, A.; Zinani, I.; Rossi, C.; Spaggiari, E.; D'Amico, V.; Toni, G.; Bedetti, L.; Lucaccioni, L.; Iughetti, L.; Lugli, L.
abstract

There is insufficient data regarding antimicrobial stewardship (AS) and outcomes of very low birth weight (VLBW) neonates after AS programs. This observational, retrospective study addressed AS and outcomes of VLBW neonates admitted to an Italian level-three center. Two periods were compared: (i) baseline, before AS (January 2011-December 2012) and (ii) intervention, after AS (January 2016-December 2017). Between these two periods, procedures were put in place to inform medical and nursing staff regarding AS. There were 111 and 119 VLBW neonates in the baseline (6744 live births) and in the intervention period (5902 live births), respectively. The number of infants exposed to antibiotics (70%) during the hospital stay did not change, but the total days of therapy (DOT, median 12 vs. 5) and DOT/1000 patient days (302 vs. 215) decreased in the intervention period (p < 0.01), as well as the median duration of first antibiotic treatment (144 vs. 48 h, p < 0.01). A re-analysis of single cases of culture-proven or culture-negative sepsis failed to demonstrate any association between deaths and a delay or insufficient antibiotic use in the intervention period. In conclusion, AS is feasible in preterm VLBW neonates and antibiotic use can be safely reduced.


2021 - Arresto di crescita nei primi mesi di vita: quando l’ipolipidemia e la steatorrea fanno diagnosi. [Abstract in Atti di Convegno]
Poluzzi, Silvia; Bruzzi, Patrizia; Trevisani, Viola; Lucaccioni, Laura; Predieri, Barbara; Madeo, Simona Filomena; Tagliafico, Enrico; Iughetti, Lorenzo
abstract


2021 - Brief comments on three existing approaches for managing neonates at risk of early-onset sepsis [Articolo su rivista]
Vaccina, E.; Luglio, A.; Ceccoli, M.; Lecis, M.; Leone, F.; Zini, T.; Toni, G.; Lugli, L.; Lucaccioni, L.; Iughetti, L.; Berardi, A.
abstract

Background: Growing concerns regarding the adverse effects of antibiotics during the first days of life and the marked reduction in the incidence of early-onset sepsis (EOS) are changing the clinical practice for managing neonates at risk of EOS. Strategies avoiding unnecessary antibiotics while promoting mother-infant bonding and breastfeeding deserve to be considered. Main body: We compare strategies for managing newborns at risk of EOS recommended by the American Academy of Pediatrics, which are among the most followed recommendations worldwide. Currently three different approaches are suggested in asymptomatic full-term or late preterm neonates: i) the conventional management, based on standard perinatal risk factors for EOS alone, ii) the neonatal sepsis calculator, a multivariate risk assessment based on individualized, quantitative risk estimates (relying on maternal risk factors for EOS) combined with physical examination findings at birth and in the following hours and iii) an approach entirely based on newborn clinical condition (serial clinical observation) during the first 48 h of life. We discuss advantages and limitations of these approaches, by analyzing studies supporting each strategy. Approximately 40% of infants who develop EOS cannot be identified on the basis of maternal RFs or laboratory tests, therefore close monitoring of the asymptomatic but at-risk infant remains crucial. A key question is to know what proportion of babies with mild, unspecific symptoms at birth can be managed safely without giving antibiotics. Conclusions: Both neonatal sepsis calculator and serial clinical observation may miss cases of EOS, and clinical vigilance for all neonates is essential There is a need to assess which symptoms at birth are more predictive of EOS, and therefore require immediate interventions, or symptoms that can be carefully reevaluated without necessarily treat immediately the neonate with antibiotics. Studies comparing strategies for managing neonates are recommended.


2021 - cardiometabolic risk in childhood cancer survivors [Articolo su rivista]
Luongo, C.; Randazzo, E.; Iughetti, L.; Di iorgi, N.; Loche, S.; Maghnie, M.; Valerio, G.; Delvecchio, M.
abstract

The Italian Cancer Registry Association has estimated that for the five-year period 2016-2020, in line with the previous five years, approximately 7000 neoplasms have been diagnosed among children and 4000 among adolescents. Leukemias, brain tumors and lymphomas together account for more than two-thirds of all pediatric cancers. Fortunately, the five-years survival rate has progressively improved reaching 80% thanks to the continuing improvement of therapeutic protocols but most of these cancer survivors will have at least one chronic health condition by 40 years of age. Long-term complications concern various organs and systems and have a multifactorial etiopathogenesis. Obesity, diabetes, and metabolic syndrome represent chronic diseases that affect life expectancy. cardiovascular risk partly linked to therapies and genetic susceptibility and partly linked to the presence of obesity, diabetes and metabolic syndrome predispose childhood cancer survivors to heart failure, coronary artery disease, valvular disease, arrhythmia. Hence the cardio- metabolic risk of childhood cancer survivors can have a significant impact on their lives, families, and on society at-large. Therefore, it is very important to know the risk factors that predispose to the development of cardio-metabolic pathologies in childhood cancer survivors, the possible primary and secondary prevention strategies, the methods of surveillance and the therapeutic approaches.


2021 - Childhood Vaccinations and Type 1 Diabetes. [Articolo su rivista]
Esposito, S; Mariotti Zani, E; Torelli, L; Scavone, S; Petraroli, M; Patianna, V; Predieri, B; Iughetti, L; Principi, N
abstract

Type 1 diabetes (T1D) is the most common paediatric endocrine disease, and its frequency has been found to increase worldwide. Similar to all conditions associated with poorly regulated glucose metabolism, T1D carries an increased risk of infection. Consequently, careful compliance by T1D children with schedules officially approved for child immunization is strongly recommended. However, because patients with T1D show persistent and profound limitations in immune function, vaccines may evoke a less efficient immune response, with corresponding lower protection. Moreover, T1D is an autoimmune condition that develops in genetically susceptible individuals and some data regarding T1D triggering factors appear to indicate that infections, mainly those due to viruses, play a major role. Accordingly, the use of viral live attenuated vaccines is being debated. In this narrative review, we discussed the most effective and safe use of vaccines in patients at risk of or with overt T1D. Literature analysis showed that several problems related to the use of vaccines in children with T1D have not been completely resolved. There are few studies regarding the immunogenicity and efficacy of vaccines in T1D children, and the need for different immunization schedules has not been precisely established. Fortunately, the previous presumed relationship between vaccine administration and T1D appears to have been debunked, though some doubts regarding rotavirus vaccines remain. Further studies are needed to completely resolve the problems related to vaccine administration in T1D patients. In the meantime, the use of vaccines remains extensively recommended in children with this disease.


2021 - Clinical presentation of celiac disease and diagnosis accuracy in a single-center european pediatric cohort over 10 years [Articolo su rivista]
Di Biase, A. R.; Marasco, G.; Ravaioli, F.; Colecchia, L.; Dajti, E.; Lecis, M.; Passini, E.; Alemanni, L. V.; Festi, D.; Iughetti, L.; Colecchia, A.
abstract

(1) Background: Changes in the clinical presentation of celiac disease (CD) in children have been reported. The guidelines of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) allow esophagogastroduodenoscopy (EGD) with biopsies to be avoided under specific circumstances. We aimed to assess the clinical picture of pediatric CD patients at diagnosis and to validate ESPGHAN non-biopsy criteria. (2) Methods: Patients with suspected CD or undergoing screening from 2004 to 2014 at the University Hospital in Modena, Italy were enrolled. The accuracy of ESPGHAN non-biopsy criteria and modified versions were assessed. (3) Results: In total, 410 patients were enrolled, of whom 403 were considered for analysis. Of the patients considered, 45 were asymptomatic and diagnosed with CD (11.2%) while 358 patients (88.2%) were symptomatic, of whom 295 were diagnosed with CD. Among symptomatic CD patients, 57 (19.3%) had gastrointestinal symptoms, 98 (33%) had atypical symptoms and 140 (47.4%) had both. No difference was found for the presence of gastrointestinal symptoms at different ages. The non-biopsy ESPGHAN criteria yielded an accuracy of 59.4% with a positive predictive value (PPV) of 100%; 173 out of 308 EGD (56.2%) could have been avoided. The modified 7× and 5× upper limit of normal cut-offs for IgA anti tissue-transglutaminase reached 60.7% and 64.3% of EGD avoided, respectively. (4) Conclusions: Over 10 years, late age at diagnosis and increased rates of atypical CD presentation were found. ESPGHAN non-biopsy criteria are accurate for CD diagnosis and allow half of unneeded EGD to be avoided. Modified versions allowed sparing a greater number of EGD.


2021 - Copy Number Variation Analysis Increases the Number of Candidate Loci Associated with Pediatric Obesity [Articolo su rivista]
Madeo, S. F.; Stanghellini, I.; Predieri, B.; Ciancia, S.; Leo, F.; Bruzzi, P.; Calabrese, O.; Iughetti, L.
abstract

Background/Aims: Obesity is a multifactorial disease caused by the interaction of genetic, environmental, and behavioral factors. Currently, only a small number of obese children undergo genetic analysis, usually when obesity is associated with dysmorphic features. The aim of this study was to identify genomic rearrangement causing obesity. Methods: We analyzed the DNA of children and adolescents by single-nucleotide polymorphism-array (platform CytoScan HD, Affymetrix). Patients included in this study were obese with dysmorphic features and/or intellectual disabilities and/or neuropsychomotor signs. Results: Ninety-four children and adolescents with obesity (9.25 ± 4.04 years old, 60 males) were enrolled in the study. Dysmorphic features were found in 64 out of 94 subjects (68.1%), intellectual disability was found in 23 subjects (24.5%), and other neuropsychomotor signs in 31 (32.9%). Copy number variations (CNVs) were identified in 43 out of 94 patients (45.7%): among these 14 subjects showed at least 1 deletion, 22 duplication, whereas 7 patients showed both deletion and duplication. In 20 subjects (13 males), CNVs were linked or possibly related with obesity; in 23 subjects, this correlation cannot be inferred. Conclusion: A genetic origin of obesity was detected in about half of our obese children and adolescents with associated dysmorphic features and/or intellectual disability and/or neuropsychomotor signs. In these children, array-CGH analysis can be useful to identify causative genetic mutations, with consequent advantage in therapeutic management and follow-up of these patients.


2021 - COVID-19 Management in the Pediatric Age: Consensus Document of the COVID-19 Working Group in Paediatrics of the Emilia-Romagna Region (RE-CO-Ped), Italy [Articolo su rivista]
Esposito, S.; Marchetti, F.; Lanari, M.; Caramelli, F.; Fanti, A. D.; Vergine, G.; Iughetti, L.; Fornaro, M.; Suppiej, A.; Zona, S.; Pession, A.; Biasucci, G.
abstract

Since December 2019, coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread, becoming the first pandemic of the 21st century by number of deaths (over 2,000,000 worldwide). Many aspects of SARS-CoV-2 infection in children and adolescents remain unclear, and optimal treatment has not yet been defined. Therefore, our goal was to develop a consensus document, practically synthesizing the accumulated data and clinical experience of our expert group. Literature research was carried out using the keywords “COVID-19” or “SARS-CoV-2” and “children” or “pediatrics” and “prevention” or “diagnosis” or “MIS-C” or “treatment” in electronic databases (MEDLINE, PUBMED), existing guidelines and gray literature. The fact that the majority of the problems posed by SARS-CoV-2 infection in pediatric age do not need hospital care and that, therefore, infected children and adolescents can be managed at home highlights the need for a strengthening of territorial pediatric structures. The sharing of hospitalization and therapeutic management criteria for severe cases between professionals is essential to ensure a fair approach based on the best available knowledge. Moreover, the activity of social and health professionals must also include the description, management and limitation of psychophysical-relational damage resulting from the SARS-CoV-2 pandemic on the health of children and adolescents, whether or not affected by COVID-19. Due to the characteristics of COVID-19 pathology in pediatric age, the importance of strengthening the network between hospital and territorial pediatrics, school, educational, social and family personnel both for strictly clinical management and for the reduction in discomfort, with priority in children of more frail families, represents a priority.


2021 - Differences between transient neonatal diabetes mellitus subtypes can guide diagnosis and therapy [Articolo su rivista]
Bonfanti, R.; Iafusco, D.; Rabbone, I.; Diedenhofen, G.; Bizzarri, C.; Patera, P. I.; Reinstadler, P.; Costantino, F.; Calcaterra, V.; Iughetti, L.; Savastio, S.; Favia, A.; Cardella, F.; Lo Presti, D.; Girtler, Y.; Rabbiosi, S.; D'Annunzio, G.; Zanfardino, A.; Piscopo, A.; Casaburo, F.; Pintomalli, L.; Russo, L.; Grasso, V.; Minuto, N.; Mucciolo, M.; Novelli, A.; Marucci, A.; Piccini, B.; Toni, S.; Silvestri, F.; Carrera, P.; Rigamonti, A.; Frontino, G.; Trada, M.; Tinti, D.; Delvecchio, M.; Rapini, N.; Schiaffini, R.; Mammi, C.; Barbetti, F.
abstract

Objective: Transient neonatal diabetes mellitus (TNDM) is caused by activating mutations in ABCC8 and KCNJ11 genes (KATP/TNDM) or by chromosome 6q24 abnormalities (6q24/TNDM). We wanted to assess whether these different genetic aetiologies result in distinct clinical features. Design: Retrospective analysis of the Italian data set of patients with TNDM. Methods: Clinical features and treatment of 22 KATP/TNDM patients and 12 6q24/TNDM patients were compared. Results: Fourteen KATP/TNDM probands had a carrier parent with abnormal glucose values, four patients with 6q24 showed macroglossia and/or umbilical hernia. Median age at diabetes onset and birth weight were lower in patients with 6q24 (1 week; -2.27 SD) than those with KATP mutations (4.0 weeks; -1.04 SD) (P = 0.009 and P = 0.007, respectively). Median time to remission was longer in KATP/TNDM than 6q24/TNDM (21.5 weeks vs 12 weeks) (P = 0.002). Two KATP/TNDM patients entered diabetes remission without pharmacological therapy. A proband with the ABCC8/L225P variant previously associated with permanent neonatal diabetes entered 7-year long remission after 1 year of sulfonylurea therapy. Seven diabetic individuals with KATP mutations were successfully treated with sulfonylurea monotherapy; four cases with relapsing 6q24/TNDM were treated with insulin, metformin or combination therapy. Conclusions: If TNDM is suspected, KATP genes should be analyzed first with the exception of patients with macroglossia and/or umbilical hernia. Remission of diabetes without pharmacological therapy should not preclude genetic analysis. Early treatment with sulfonylurea may induce long-lasting remission of diabetes in patients with KATP mutations associated with PNDM. Adult patients carrying KATP/TNDM mutations respond favourably to sulfonylurea monotherapy.


2021 - Disorder of sex development associated with a novel homozygous nonsense mutation in COG6 expands the phenotypic spectrum of COG6-CDG [Articolo su rivista]
Lugli, L.; Bariola, M. C.; Ferri, L.; Lucaccioni, L.; Bertucci, E.; Cattini, U.; Torcetta, F.; Morrone, A.; Iughetti, L.; Berardi, A.
abstract

Congenital disorders of glycosylation (CDG) are an expanding group of metabolic disorders that result from abnormal protein glycosylation. A special subgroup of CDG type II comprises defects in the Conserved Oligomeric Golgi Complex (COG). In order to further delineate the genotypic and phenotypic spectrum of COG complex defect, we describe a novel variant of COG6 gene found in homozygosity in a Moroccan patient with severe presentation of COG6-CDG (OMIM #614576). We compared the phenotype of our patient with other previously reported COG6-CDG cases. Common features in COG6-CDG are facial dysmorphism, growth retardation, microcephaly, developmental disability, liver or gastrointestinal disease, recurrent infections, hypohidrosis/hyperthermia. In addition to these phenotypic features, our patient exhibited a disorder of sexual differentiation, which has rarely been reported in COG6-CDG. We hypothesize that the severe COG6 gene mutation interferes with glycosylation of a disintegrin and metalloprotease family members, inhibiting the correct gonadal distal tip cells migration, fundamental for the genitalia morphogenesis. This report broadens the genetic and phenotypic spectrum of COG6-CDG and provides further supportive evidence that COG6-CDG can present as a disorder of sexual differentiation.


2021 - Eeg patterns in patients with prader–willi syndrome [Articolo su rivista]
Elia, M.; Rutigliano, I.; Sacco, M.; Madeo, S. F.; Wasniewska, M.; Li Pomi, A.; Trifiro, G.; Di Bella, P.; De Lucia, S.; Vetri, L.; Iughetti, L.; Delvecchio, M.
abstract

Prader–Willi syndrome (PWS) is a rare disease determined by the loss of the paternal copy of the 15q11-q13 region, and it is characterized by hypotonia, hyperphagia, obesity, short stature, hypogonadism, craniofacial dysmorphisms, and cognitive and behavioral disturbances. The aims of this retrospective study were to analyze interictal EEG findings in a group of PWS patients and to correlate them with genetic, clinical, and neuroimaging data. The demographic, clinical, genetic, EEG, and neuroimaging data of seventy-four patients were collected. Associations among the presence of paroxysmal EEG abnormalities, genotype, and clinical and neuroimaging features were investigated. Four patients (5.4%) presented drug-sensitive epilepsy. Interictal paroxysmal EEG abnormalities—focal or multifocal—were present in 25.7% of the cases, and the normalization of the EEG occurred in about 25% of the cases. In 63.2% of the cases, the paroxysmal abnormalities were bilaterally localized over the middle–posterior regions. Brain magnetic resonance imaging (MRI) was performed on 39 patients (abnormal in 59%). No relevant associations were found between paroxysmal EEG abnormalities and all of the other variables considered. Interictal paroxysmal EEG abnormalities—in particular, with a bilateral middle–posterior localization—could represent an important neurological feature of PWS that is not associated with genotype, cognitive or behavioral endophenotypes, MRI anomalies, or prognosis.


2021 - Effects of 1-year COVID-19 pandemic on auxological parameters and metabolic control in young patients with type 1 diabetes [Abstract in Rivista]
Iughetti, L.; Bruzzi, P.; Caccamo, P.; Di Caprio, A.; Trevisani, V.; Predieri, B.
abstract

Introduction: Since the beginning of the SARS-CoV-2 infection, concerns for consequences on auxological and glycemic control data in patients with type 1 diabetes (T1D) were raised. Objectives: To investigate 1-year effects of the COVID-19 pandemic on auxological parameters and metabolic control in youths with T1D. Methods: Anthropometric (height [Ht], weight, waist circumference [W]) and glycemic control data of patients with T1D were collected during the annual routine outpatient visit between Dec20-Feb21 (1-year after the pandemic) and were compared with the ones of the same period in 2019-20 (before the closure of schools and organized sport activities). Results: Seventy-eight children and adolescents with T1D (61.5% male; median age 13.7 [5.7-17.8] years; T1D duration 5.96 [2.1-15.4] years) were enrolled. Patients affected by SARS-CoV-2 infection were 15.4% (second wave). In Dec20-Feb21, BMI SDS and WHt ratio remained comparable to the year before lockdown. CGM use increased during the pandemic period (67.9 vs 71.8%, p<0.0001). Annual number of outpatient visits decreased (4 vs 3, p<0.0001), while telemedicine increased because 56.4% of patients had at least one telemedicine visit during pandemic (none before). Rate of DKA remained comparable (1.82 vs 2.56%) and no severe hypoglycemic event was recorder during pandemic (2.56 vs. 0%). Physical activity decreased (2 vs 0 h/week, p<0.001) and insulin TDD increased (0.84 vs 0.94 IU/kg/day, p=0.029). Average annual HbA1c values were comparable (62 vs 60 mmol/mol) and prevalence of patients with the last HbA1c value ≤53 mmol/mol increased (24 vs 28%, p<0.0001). Conclusions: In our patients with T1D, BMI SDS and glycemic control were maintained during the 1-year pandemic period despite the decrease of physical activity. Our data may be possibly related to the increase of telemedicine visits that allowed us to adjust patients' insulin TDD, to avoid acute complications, and also to continue educational training to start CGM, complying with safety rules to avoid COVID-19 spread.


2021 - EFFETTI DI UN ANNO DI PANDEMIA COVID-19 SU PARAMETRI AUXOLOGICI E CONTROLLO METABOLICO NEI BAMBINI ED ADOLESCENTI CON DIABETE DI TIPO 1. [Abstract in Atti di Convegno]
Iughetti, Lorenzo; Bruzzi, Patrizia; Caccamo, Paola; Di Caprio, Antonella; Trevisani, Viola; Predieri, Barbara
abstract


2021 - Elevata incidenza di Diabete tipo 1 tra i bambini di famiglie migranti provenienti dal Nord Africa nella regione Emilia Romagna. [Abstract in Atti di Convegno]
Maltoni, Giulio; Iughetti, Lorenzo; Predieri, Barbara; Bruzzi, Patrizia; Iovane, Brunella; Lazzeroni, Pietro; Graziani, Vanna; Suprani, Tosca; Monti, Sara; Elisabeth Street, Maria; Lasagni, Anna; De Luca, Francesca; Libertucci, Francesca; Mainetti, Benedetta; Riboni, Sara; Sogno Valin, Paola
abstract


2021 - Etiology and management of pediatric intestinal failure: Focus on the non-digestive causes [Articolo su rivista]
Diamanti, A.; Calvitti, G.; Martinelli, D.; Santariga, E.; Capriati, T.; Bolasco, G.; Iughetti, L.; Pujia, A.; Knafelz, D.; Maggiore, G.
abstract

Background: Intestinal failure (IF) is defined as reduction in functioning gut mass below the minimal amount necessary for adequate digestion and absorption. In most cases, IF results from intrinsic diseases of the gastrointestinal tract (digestive IF) (DIF); few cases arise from digestive vascular components, gut annexed (liver and pancreas) and extra-digestive organs or from systemic diseases (non-digestive IF) (NDIF). The present review revised etiology and treatments of DIF and NDIF, with special focus on the pathophysiological mechanisms, whereby NDIF develops. Methods: We performed a comprehensive search of published literature from January 2010 to the present by selecting the following search strings: “intestinal failure” OR “home parenteral nutrition” OR “short bowel syndrome” OR “chronic pseudo-obstruction” OR “chronic intestinal pseudo-obstruction” OR “autoimmune enteropathy” OR “long-term parenteral nutrition”. Results: We collected overall 1656 patients with well-documented etiology of IF: 1419 with DIF (86%) and 237 with NDIF (14%), 55% males and 45% females. Among DIF cases, 66% had SBS and among NDIF cases 90% had malabsorption/maldigestion. Conclusions: The improved availability of diagnostic and therapeutic tools has increased prevalence and life expectancy of rare and severe diseases responsible for IF. The present review greatly expands the spectrum of knowledge on the pathophysiological mechanisms through which the diseases not strictly affecting the intestine can cause IF. In view of the rarity of the majority of pediatric IF diseases, the development of IF Registries is strongly required; in fact, through information flow within the network, the Registries could improve IF knowledge and management.


2021 - Fallot's tetralogy and squatting position [Articolo su rivista]
Pique, M.; Brasili, L.; Putoto, G.; Iughetti, L.
abstract

The paper presents the case of a 1-year-old girl with severe respiratory distress, perioral cyanosis and severe desaturation (SpO2 35% with oxygen in nasal prongs).An echocardiogram was readily performed showing the distinctive features of Fallot’s tetralogy.The child was placed in a squatting position (knee-chest position). Subcutaneous morphine at a dose of 0.2 mg/kg, bolus of physiological solution in 30 minutes and therapy with oral propanolol were administered, with progressive clinical improvement. Subsequently, corrective cardiac surgery was performed with regular postoperative period and following good clinical conditions. Cardiogenic causes must be considered among the causes of respiratory distress especially in low resource countries where congenital heart disease can be misdiagnosed or diagnosed belatedly.


2021 - Gestione del Covid-19 in età pediatrica: documento di consenso [Articolo su rivista]
Esposito, Susanna; Marchetti, Federico; Lanari, Marcello; Caramelli, Fabio; DE FANTI, Alessandro; Vergine, Gianluca; Iughetti, Lorenzo; Fornaro, Martina; Suppiej, Agnese; Zona, Stefano; Pession, Andrea; Biasucci, Giacomo; DI LAVORO SU COVID-19 IN PEDIATRIA DELLA REGIONE EMILIA-ROMAGNA(Giuseppe Cannalire, Gruppo; Sole Magistrali, Maria; Akamin, Raymond; Dodi, Icilio; Argentiero, Alberto; Abate, Luciana; De Guido, Claudia; Fanelli, Umberto; Pappalardo, Marco; Pecora, Francesco; Sogni, Francesco; Gargano, Giancarlo; Volta, Alessandro; Panza, Costantino; Fornaciari, Sara; Russo, Giovanna; Predieri, Barbara; Chiarolanza, Jennifer; Andreozzi, Laura; Fabi, Marianna; Sandri, Fabrizio; Ghizzi, Chiara; Ricci, Rita; Nicoli, Luciana; Ballestrazzi, Alessandro; Dall’Osso, Tiziano; Serra, Laura; Guiducci, Claudia; Iacono, Alessandra; Maria Magistà, Anna; Malaventura, Cristina; Fumarola, Adriana; Bergamini, Marcello; Valletta, Enrico; Stella, Marcello; Mazzini, Franco; Ancora, Gina; Pancaldi, Giovanni; Scarpellini, Beatrice; Ferrè, Cristina; De Palma, Rossana; Di Mario, Simona; Franchi, Fabia; Giroldini, Roberta; Maria Marata, Anna; Mattei, Giovanna; Solfrini, Valentina; Luisa Moro), Maria
abstract

Coronavirus disease 2019 (Covid-19) caused by SARS-CoV-2 has rapidly spread, becoming the first pandemic of the 21st century by death toll. Children appear to be less affected than adults, with a milder clinical presentation and a significantly lower mortality rate. However, serious complica-tions can occur in childhood, such as Covid-19 temporally related multisystem inflammatory syn-drome (MIS-C). Some aspects of SARS-CoV-2 infection in children and adolescents remain un-clear and the optimal treatment has not been defined. The Working Group on Covid-19 in Paediatrics of the Emilia-Romagna Region (RE-CO-PED) has produced a consensus document with practical recommendations based on a systematic review of the literature and on the clinical experi-ence of the expert group. Evidence is reported regarding prevention measures, diagnostic tools as well as home and hospital therapeutic management of complicated cases (MIS-C). The educational and psychological effects of the pandemic in the paediatric and adolescent age are reported, with the need to define coordinated interventions (between paediatricians, neurospychiatrists, psycholo-gists and educational services) for the prevention and treatment of documented emotional, relational and educational consequences caused by the lockdown, school closures and social distances.


2021 - Global perspective of familial hypercholesterolaemia: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC) [Articolo su rivista]
Vallejo-Vaz, A. J.; Stevens, C. A. T.; Lyons, A. R. M.; Dharmayat, K. I.; Freiberger, T.; Hovingh, G. K.; Mata, P.; Raal, F. J.; Santos, R. D.; Soran, H.; Watts, G. F.; Abifadel, M.; Aguilar-Salinas, C. A.; Alhabib, K. F.; Alkhnifsawi, M.; Almahmeed, W.; Alnouri, F.; Alonso, R.; Al-Rasadi, K.; Al-Sarraf, A.; Al-Sayed, N.; Araujo, F.; Ashavaid, T. F.; Banach, M.; Beliard, S.; Benn, M.; Binder, C. J.; Bogsrud, M. P.; Bourbon, M.; Chlebus, K.; Corral, P.; Davletov, K.; Descamps, O. S.; Durst, R.; Ezhov, M.; Gaita, D.; Genest, J.; Groselj, U.; Harada-Shiba, M.; Holven, K. B.; Kayikcioglu, M.; Khovidhunkit, W.; Lalic, K.; Latkovskis, G.; Laufs, U.; Liberopoulos, E.; Lima-Martinez, M. M.; Lin, J.; Maher, V.; Marais, A. D.; Marz, W.; Mirrakhimov, E.; Miserez, A. R.; Mitchenko, O.; Nawawi, H.; Nordestgaard, B. G.; Panayiotou, A. G.; Paragh, G.; Petrulioniene, Z.; Pojskic, B.; Postadzhiyan, A.; Raslova, K.; Reda, A.; Reiner, ; Sadiq, F.; Sadoh, W. E.; Schunkert, H.; Shek, A. B.; Stoll, M.; Stroes, E.; Su, T. -C.; Subramaniam, T.; Susekov, A. V.; Tilney, M.; Tomlinson, B.; Truong, T. H.; Tselepis, A. D.; Tybjaerg-Hansen, A.; Vazquez Cardenas, A.; Viigimaa, M.; Wang, L.; Yamashita, S.; Kastelein, J. J. P.; Bruckert, E.; Vohnout, B.; Schreier, L.; Pang, J.; Ebenbichler, C.; Dieplinger, H.; Innerhofer, R.; Winhofer-Stockl, Y.; Greber-Platzer, S.; Krychtiuk, K.; Speidl, W.; Toplak, H.; Widhalm, K.; Stulnig, T.; Huber, K.; Hollerl, F.; Rega-Kaun, G.; Kleemann, L.; Maser, M.; Scholl-Burgi, S.; Saly, C.; Mayer, F. J.; Sablon, G.; Tarantino, E.; Nzeyimana, C.; Pojskic, L.; Sisic, I.; Nalbantic, A. D.; Jannes, C. E.; Pereira, A. C.; Krieger, J. E.; Petrov, I.; Goudev, A.; Nikolov, F.; Tisheva, S.; Yotov, Y.; Tzvetkov, I.; Baass, A.; Bergeron, J.; Bernard, S.; Brisson, D.; Brunham, L. R.; Cermakova, L.; Couture, P.; Francis, G. A.; Gaudet, D.; Hegele, R. A.; Khoury, E.; Mancini, G. B. J.; Mccrindle, B. W.; Paquette, M.; Ruel, I.; Cuevas, A.; Asenjo, S.; Wang, X.; Meng, K.; Song, X.; Yong, Q.; Jiang, T.; Liu, Z.; Duan, Y.; Hong, J.; Ye, P.; Chen, Y.; Qi, J.; Liu, Z.; Li, Y.; Zhang, C.; Peng, J.; Yang, Y.; Yu, W.; Wang, Q.; Yuan, H.; Cheng, S.; Jiang, L.; Chong, M.; Jiao, J.; Wu, Y.; Wen, W.; Xu, L.; Zhang, R.; Qu, Y.; He, J.; Fan, X.; Wang, Z.; Chow, E.; Pecin, I.; Perica, D.; Symeonides, P.; Vrablik, M.; Ceska, R.; Soska, V.; Tichy, L.; Adamkova, V.; Franekova, J.; Cifkova, R.; Kraml, P.; Vonaskova, K.; Cepova, J.; Dusejovska, M.; Pavlickova, L.; Blaha, V.; Rosolova, H.; Nussbaumerova, B.; Cibulka, R.; Vaverkova, H.; Cibickova, L.; Krejsova, Z.; Rehouskova, K.; Malina, P.; Budikova, M.; Palanova, V.; Solcova, L.; Lubasova, A.; Podzimkova, H.; Bujdak, J.; Vesely, J.; Jordanova, M.; Salek, T.; Urbanek, R.; Zemek, S.; Lacko, J.; Halamkova, H.; Machacova, S.; Mala, S.; Cubova, E.; Valoskova, K.; Burda, L.; Bendary, A.; Daoud, I.; Emil, S.; Elbahry, A.; Rafla, S.; Sanad, O.; Kazamel, G.; Ashraf, M.; Sobhy, M.; El-Hadidy, A.; Shafy, M. A.; Kamal, S.; Bendary, M.; Talviste, G.; Angoulvant, D.; Boccara, F.; Cariou, B.; Carreau, V.; Carrie, A.; Charrieres, S.; Cottin, Y.; Di-Fillipo, M.; Ducluzeau, P. H.; Dulong, S.; Durlach, V.; Farnier, M.; Ferrari, E.; Ferrieres, D.; Ferrieres, J.; Gallo, A.; Hankard, R.; Inamo, J.; Lemale, J.; Moulin, P.; Paillard, F.; Peretti, N.; Perrin, A.; Pradignac, A.; Rabes, J. P.; Rigalleau, V.; Sultan, A.; Schiele, F.; Tounian, P.; Valero, R.; Verges, B.; Yelnik, C.; Ziegler, O.; Haack, I. A.; Schmidt, N.; Dressel, A.; Klein, I.; Christmann, J.; Sonntag, A.; Stumpp, C.; Boger, D.; Biedermann, D.; Usme, M. M. N.; Beil, F. U.; Klose, G.; Konig, C.; Gouni-Berthold, I.; Otte, B.; Boll, G.; Kirschbaum, A.; Merke, J.; Scholl, J.; Segiet, T.; Gebauer, M.; Predica, F.; Mayer, M.; Leistikow, F.; Fullgraf-Horst, S.; Muller, C.; Schuler, M.; Wiener, J.; Hein, K.; Baumgartner, P.; Kopf, S.; Busch, R.; Schomig, M.; Matthias, S.; Allendorf-Ostwald, N.; Fink, B.; Bohm, D.; Jakel, A.; Koschker, A. -C.; Schweizer, R.; Vogt, A.; Parhofer, K.;
abstract

Background: The European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC) global registry provides a platform for the global surveillance of familial hypercholesterolaemia through harmonisation and pooling of multinational data. In this study, we aimed to characterise the adult population with heterozygous familial hypercholesterolaemia and described how it is detected and managed globally. Methods: Using FHSC global registry data, we did a cross-sectional assessment of adults (aged 18 years or older) with a clinical or genetic diagnosis of probable or definite heterozygous familial hypercholesterolaemia at the time they were entered into the registries. Data were assessed overall and by WHO regions, sex, and index versus non-index cases. Findings: Of the 61 612 individuals in the registry, 42 167 adults (21 999 [53·6%] women) from 56 countries were included in the study. Of these, 31 798 (75·4%) were diagnosed with the Dutch Lipid Clinic Network criteria, and 35 490 (84·2%) were from the WHO region of Europe. Median age of participants at entry in the registry was 46·2 years (IQR 34·3–58·0); median age at diagnosis of familial hypercholesterolaemia was 44·4 years (32·5–56·5), with 40·2% of participants younger than 40 years when diagnosed. Prevalence of cardiovascular risk factors increased progressively with age and varied by WHO region. Prevalence of coronary disease was 17·4% (2·1% for stroke and 5·2% for peripheral artery disease), increasing with concentrations of untreated LDL cholesterol, and was about two times lower in women than in men. Among patients receiving lipid-lowering medications, 16 803 (81·1%) were receiving statins and 3691 (21·2%) were on combination therapy, with greater use of more potent lipid-lowering medication in men than in women. Median LDL cholesterol was 5·43 mmol/L (IQR 4·32–6·72) among patients not taking lipid-lowering medications and 4·23 mmol/L (3·20–5·66) among those taking them. Among patients taking lipid-lowering medications, 2·7% had LDL cholesterol lower than 1·8 mmol/L; the use of combination therapy, particularly with three drugs and with proprotein convertase subtilisin–kexin type 9 inhibitors, was associated with a higher proportion and greater odds of having LDL cholesterol lower than 1·8 mmol/L. Compared with index cases, patients who were non-index cases were younger, with lower LDL cholesterol and lower prevalence of cardiovascular risk factors and cardiovascular diseases (all p<0·001). Interpretation: Familial hypercholesterolaemia is diagnosed late. Guideline-recommended LDL cholesterol concentrations are infrequently achieved with single-drug therapy. Cardiovascular risk factors and presence of coronary disease were lower among non-index cases, who were diagnosed earlier. Earlier detection and greater use of combination therapies are required to reduce the global burden of familial hypercholesterolaemia. Funding: Pfizer, Amgen, Merck Sharp & Dohme, Sanofi–Aventis, Daiichi Sankyo, and Regeneron.


2021 - Growth hormone deficiency in a child with benign hereditary chorea caused by a de novo mutation of the TITF1/NKX2-1 gene [Articolo su rivista]
Trevisani, V.; Predieri, B.; Madeo, S. F.; Fusco, C.; Garavelli, L.; Caraffi, S.; Iughetti, L.
abstract

Benign Hereditary Chorea (BHC) (MIM 118700) is a rare childhood-onset movements disorder characterized by non-progressive chorea. It is usually caused by variants in the thyroid transcription factor 1 (TITF-1/NKX2-1) gene and it is associated with thyroid dysfunction and pulmonary symptoms in the brain-lung-thyroid syndrome. We reported the clinical case of a toddler presenting with neurological symptoms (hypotonia, delayed motor milestones, and axial dystonia) and subclinical hypothyroidism in which we found a 'de novo' variant in the NKX2-1 gene. The peculiarity of our case is that the mild alteration of thyroid-stimulating hormone (TSH) levels, hypotonia, and delayed motor milestones were associated with growth hormone deficiency.


2021 - Gut microbiota signatures and clinical manifestations in celiac disease children at onset: a pilot study [Articolo su rivista]
Di Biase, Anna Rita; Marasco, Giovanni; Ravaioli, Federico; Dajti, Elton; Colecchia, Luigi; Righi, Beatrice; D'Amico, Virginia; Festi, Davide; Iughetti, Lorenzo; Colecchia, Antonio
abstract

Recent researches have shown an altered gut microbiota in celiac disease (CD) patients compared with healthy controls (HCs). This study aims to evaluate the composition of the microbiota of CD children at onset and the relationship between bacterial abundances and symptoms.


2021 - Health-related quality of life and metabolic control in young patients with type 1 diabetes and in their parents before and after the COVID-19 lockdown [Abstract in Rivista]
Predieri, B.; Bruzzi, P.; Candia, F.; Caccamo, P.; Sandoni, M.; Stefanelli, F.; Pugliese, M.; Lucaccioni, L.; Madeo, S. F.; Iughetti, L.
abstract

Introduction: Since the beginning of the COVID-19 pandemic, concerns for consequences in patients with type 1 diabetes (T1D) were raised. Objectives: To compare the diabetes-specific health-related quality of life (D-HRQOL) of youths with T1D and their parents before and after the COVID-19-related lockdown. Methods: The Pediatric Quality of Life Inventory™ 3.0 Diabetes Module (PedsQL™ 3.0 DM) was used to evaluate the D-HRQOL. Patients who filled the D-HRQOL before lockdown (Dec-19–Feb-20; T0) were recruited in the study and filled the same survey immediately after the lockdown was stopped (Jun-20; T1) during a routine outpatient or telemedicine visit. Results: Sixty-two patients (median age: 12.6 [5.25-17.8] yrs; T1D duration 4.23 [0.45- 16.4] yrs) with T1D and their parents (60 mothers, 10 fathers) were enrolled. Patients' scales scores did not significantly change from T0 to T1. Mothers significantly increased their Diabetes symptoms scale score (median 67.0 vs. 70.4; p=0.007). Data were also analyzed according to visit type (outpatient vs. telemedicine), glucose monitoring (SBGM vs. isCGM vs. rtCGM), and insulin therapy (MDI vs. CSII), but D-HRQOL data were longitudinally comparable and no difference was found between groups. During lockdown no DKA, severe hypoglycemic events, and SARS-CoV-2 were recorded. Despite the significant decrease of exercise (median 3.25 vs. 0.50 h/week; p<0.0001), median glycemic control (HbA1c 58.5 vs. 57.9 mmol/mol) and total daily insulin dose (0.86 vs. 0.82 IU/kg/day) were unchanged. At T1, the lower the HbA1c, the better patients' Diabetes symptoms (R=-0.41, p<0.001), Worry (R=-0.27, p=0.032) scales, and total scores (R=-0.33, p=0.009). Similar results were found in parents. Conclusions: During COVID-19 pandemic-related lockdown the D-HRQOL did not change in children and adolescents with T1D and their parents. Our data may be possibly related to staying at home, making diabetes managements easier and also allowing the maintenance of good glycemic control without acute complications.


2021 - Heart failure caused by VGAM: a lesson for diagnosis and treatment from a case and literature review [Articolo su rivista]
Spada, C.; Pietrella, E.; Caramaschi, E.; Bergonzini, P.; Berardi, A.; Lucaccioni, L.; Iughetti, L.
abstract

We describe the case of a neonate with signs of heart failure. Echocardiography showed a structural normal heart shape with left ventricular dysfunction. At 2 months of age, a vein of Galen arteriovenous malformation was diagnosed through a brain magnetic resonance imaging. Embolization therapy was accomplished and a clinical and neurological follow-up was started. This clinical case highlights how important it is considering an intracranial cause in the differential diagnosis of neonatal congestive heart failure (CHF). We performed a narrative minireview of the literature about treatments and outcome of this malformation in association to CHF, to point out how complex the diagnosis of vein of Galen aneurysmal malformation (VGAM) may be and how an early diagnosis is important for its management.


2021 - High incidence of type 1 diabetes among children of North African migrants in Emilia-Romagna Region, Italy [Abstract in Rivista]
Maltoni, G.; Zioutas, M.; Iughetti, L.; Predieri, B.; Iovane, B.; Lazzeroni, P.; Street, M. E.; Lasagni, A.; Graziani, V.; Suprani, T.; De Luca, F.; Riboni, S.; Sogno Valin, P.; Mainetti, B.; Libertucci, F.; Zucchini, S.
abstract

In the last few decades, many studies have reported an increasing global incidence of Type 1 Diabetes (T1D), especially in younger children. The differences between different ethnic and age groups have underlined both the importance of environmental and genetic factors in the development of the pathology, as studies on migrant populations have already demonstrated. Objectives: Evaluate the incidence of T1D and DKA prevalence in North African vs Italian children aged 0 to 14 years from 1st January 2015 to 31st December 2018, in Emilia Romagna Region, Italy. Methods: Clinical and epidemiological data about childhood onset T1D in E-R region were retrospectively collected and matched using 3 different data sources (Clinical registries, hospital discharge records and regional lists of exemptions for pathology). T1D cumulative incidence was calculated basing on the number of inhabitants in the region as a whole and subdividing the Italian and North African groups. Results: 365 new T1D onset were diagnosed (M 50.1%). DKA was present in 33% of cases (severe DKA 10.4%). Median age at T1D onset was 8.2 ± 3.7 yrs. Total cumulative incidence was 15.4/100.000/year and no increasing trend was recorded in the incidence of diabetes in the study period. In particular, North African cases were 52 with a cumulative incidence of 62.2/100.000/year, statistically significant compared to cumulative incidence of the Italian cases alone 13.1/100.000/year (p value <0.001). The annual incidence did not differ in the 4 years for both groups. No difference as for DKA cases and median age at T1D onset between the groups. Conclusions: The incidence of T1D in the pediatric age was significantly higher in the North African population than in the Italian one. Surprisingly, the incidence was much higher than not only that of the host country, but also of the country of origin, suggesting an explosive mix of genetic and environmental factors causing the increase in newly diagnosed cases.


2021 - Homozygous n.64C>T mutation in mitochondrial RNA-processing endoribonuclease gene causes cartilage hair hypoplasia syndrome in two siblings [Articolo su rivista]
Lugli, L.; Ciancia, S.; Bertucci, E.; Lucaccioni, L.; Calabrese, O.; Madeo, S.; Berardi, A.; Iughetti, L.
abstract

Cartilage hair hypoplasia syndrome (OMIM # 250250) is a rare autosomal recessive metaphyseal dysplasia, characterized by disproportionate short stature, hair hypoplasia and variable extra-skeletal manifestations, including immunodeficiency, anemia, intestinal diseases and predisposition to cancers. Cartilage hair hypoplasia syndrome has a broad phenotype and it is caused by homozygous or compound heterozygous mutation in the mitochondrial RNA-processing endoribonuclease on chromosome 9p13. Although it is well known as a primordial dwarfism, descriptions of the prenatal growth are missing. To add further details to the knowledge of the phenotypic spectrum of the disease, we report on two siblings with cartilage hair hypoplasia syndrome, presenting n.64C > T homozygous mutation in the mitochondrial RNA-processing endoribonuclease gene. We describe the prenatal and postnatal growth pattern of the two affected patients, showing severe pre- and post-natal growth deficiency.


2021 - Hypospadias: clinical approach, surgical technique and long-term outcome [Articolo su rivista]
Ceccarelli, P. L.; Lucaccioni, L.; Poluzzi, F.; Bianchini, A.; Biondini, D.; Iughetti, L.; Predieri, B.
abstract

Background: Hypospadias is one of the most common congenital abnormalities in male newborn. There is no universal approach to hypospadias surgical repair, with more than 300 corrective procedures described in current literature. The reoperation rate within 6–12 months of the initial surgery is most frequently used as an outcome measure. These short-term outcomes may not reflect those encountered in adolescence and adult life. This study aims to identify the long-term cosmetic, functional and psychosexual outcomes. Methods: Medical records of boys who had undergone surgical repair of hypospadias by a single surgical team led by the same surgeon at a single centre between August 2001 and December 2017 were reviewed. Families were contacted by telephone and invited to participate. Surgical outcome was assessed by combination of clinical examination, a life-related interview and 3 validated questionnaires (the Penile Perception Score-PPS, the Hypospadias Objective Score Evaluation-HOSE, the International Index of Erectile Function-5-IIEF5). Outcomes were compared according to age, severity of hypospadias, and respondent (child, parent and surgeon). Results: 187 children and their families agreed to participate in the study. 46 patients (24.6%) presented at least one complication after the repair, with a median elapsed time of 11.5 months (6.5–22.5). Longitudinal differences in surgical corrective procedures (p < 0.01), clinical approach (p < 0.01), hospitalisation after surgery (p < 0.01) were found. Cosmetic data from the PPS were similar among children and parents, with no significant differences in child’s age or the type of hypospadias: 83% of children and 87% of parents were satisfied with the cosmetic result. A significant difference in functional outcome related to the type of hypospadias was reflected responses to HOSE amongst all groups of respondents: children (p < 0.001), parents (p=0.02) and surgeon (p < 0.01). The child’s HOSE total score was consistently lower than the surgeon (p < 0.01). The HOSE satisfaction rate on functional outcome was 89% for child and 92% for parent respondents. Conclusion: Surgeons and clinicians should be cognizant of the long-term outcomes following hypospadias surgical repair and this should be reflected in a demand for a standardised approach to repair and follow-up.


2021 - In pazienti con deficit isolato idiopatico di ormone della crescita (IIGHD) in trattamento con GH, il network dei miRNA si modifica e regola pathways coinvolti nella crescita e nel cancro [Abstract in Atti di Convegno]
Catellani, Cecilia; Ravegnini, Gloria; Sartori, Chiara; Righi, Beatrice; Poluzzi, Silvia; Predieri, Barbara; Iughetti, Lorenzo; Angelini, Sabrina; ELISABETH STREET, Maria
abstract


2021 - Incidental pituitary adenoma detection in two patients affected by Williams Syndrome: only a coincidence? [Abstract in Rivista]
Ciancia, Silvia; Madeo, Simona F.; Cattini, Umberto; Bruzzi, Patrizia; Lucaccioni, Laura; Predieri, Barbara; Iughetti, Lorenzo
abstract


2021 - Internal Carotid Dissection as the Cause of Stroke in Childhood [Articolo su rivista]
Cinelli, Giulia; Loizzo, Vitaliana; Montanari, Lisa; Filareto, Ilaria; Caramaschi, Elisa; Predieri, Barbara; Iughetti, Lorenzo
abstract

Internal carotid artery (ICA) dissection is a cause of stroke, but it is often underdiagnosed in children. ICAs’ risk factors and pathogenic mechanisms are poorly understood, and the treatment is still empirical. We report the case of a previously healthy 9-year-old girl who presented with involuntary hypertonic closure of the right hand associated with transient difficulty for both fine movements of the right arm and speech. She had a history of minor cervical trauma occurring 20 days prior to our observation without other associated risk factors. Magnetic resonance imaging and magnetic resonance angiography showed ischemic lesions due to the left ICA dissection. Treatment with both acetylsalicylic acid and levetiracetam allowed recanalization of the ICA associated with the resolution of clinical signs. Our clinical case suggests that the ICA dissection must be suspected early whenever a child manifests mild neurologic deficits after a cervical trauma, especially if they are associated with headache and/or cervical pain. Moreover, the management of ICA dissection must be improved.


2021 - Late diagnosis of severe long-standing autoimmune hypothyroidism after the first lockdown for the Covid-19 pandemic: clinical features and follow-up [Articolo su rivista]
Mansueto, M. L.; Zagni, G.; Sartori, C.; Bermudez, B. A. O.; Righi, B.; Catellani, C.; Fusco, C.; Frasoldati, A.; De Fanti, A.; Iughetti, L.; Street, M. E.
abstract

Background and aim: Hashimoto’s thyroiditis (HT) is a common endocrinopathy in children, particularly in females. Clinical overt presentation of hypothyroidism in HT includes mild to very severe forms, characterised by impairment of many body functions and organs, such as heart, brain, muscles, ovaries and liver. Case: we report the case of a 14-year-old girl, with severe hypothyroidism due to a late diagnosis of HT during the Covid-19 pandemic. Routine biochemical and hormonal exams were carried out at presentation. Moderate pericardial effusion was detected by echocardiography and polycystic ovarian morphology (PCOM) was found on the pelvic ultrasound. Furthermore, high levels of creatine phosphokinase (CPK), Lactic Acid Dehydrogenase (LDH) and hepatic liver enzymes, associated with muscular pseudohypertrophy and bilateral weakness of the lower limbs, were suggestive of a rare presentation of long-standing hypothyroidism defined Kocher-Debre-Semelaigne syndrome (KDSS). Levothyroxine replacement therapy was started immediately, leading to a rapid improvement of symptoms and a progressive normalization of the biochemical parameters. Due to persistent lower limb weakness, further neurological investigations were performed, showing bilateral peripheral polyneuropathy (PNP), ascribable to the longstanding and severe hypothyroidism. A pelvic ultrasound, performed after thyroid hormones had normalised and menses had turned to be regular, showed normal ovarian features supporting the hypothesis of the Van Wyk and Grumbach syndrome in a postmenarcheal girl. Conclusions: although clinical manifestation of hypothyroidism are usually mild, more severe and rare presentations such as ovarian dysfunction and myopathy are possible, particularly if the diagnosis is delayed and replacement therapy is not promptly administered.


2021 - Long term outcomes of infants born by mothers with thyroid dysfunction during pregnancy [Articolo su rivista]
Lucaccioni, L.; Ficara, M.; Cenciarelli, V.; Berardi, A.; Predieri, B.; Iughetti, L.
abstract

According to Barker’s hypothesis, sub-optimal conditions during gestation might affect the pre-disposition for diseases in adulthood. Alteration in endocrine functions during pregnancy, such us thyroid function or glucose metabolism, are not exempt. It is well known that subclinical hypothyroidism and thy-roperoxidase antibodies-positive euthyroidism during early pregnancy are associated with increased risk of gestational diabetes mellitus and both conditions influence pregnancy outcome and newborn development and metabolism at short and long terms. Fetal production of thyroid hormones starts from the 12th week of gestational age. The transplacental passage of maternal thyroxine (T4) is therefore essential for the fetal neu-rological development, especially during the first half of pregnancy. If this passage is interrupted, such as in premature birth, neonates are more susceptible to develop impaired thyroid function, because of physiological immaturity of their hypothalamic-pituitary-thyroid axis, acute illnesses and stressful events (sepsis, invasive procedures, drugs). The aim of this review is to investigate the short and long term effects of maternal dysthy-roidisms on term and preterm newborns, with particular attention to the metabolic and thyroid consequences. Metabolic syndrome, higher body mass index and greater waist circumference, seem to be more prevalent in children of TPO-Ab-positive mothers. Maternal hypothyroidism may be associated with higher risk of gestational diabetes and adverse birth outcomes, such as preeclampsia, preterm delivery, fetal death and low birth weight offspring. In adulthood, preterm (< 37 weeks of gestational age) or low birth weight (<2.500 g) newborns seem to be more susceptible to develop gestational diabetes, preeclampsia, type 2 diabetes mellitus and behavioral alterations. (www.actabiomedica.it).


2021 - Longitudinal evaluation of endothelial markers in children and adolescents with familial hypercholesterolemia [Articolo su rivista]
Bruzzi, Patrizia; Predieri, Barbara; Madeo, Simona; Lami, Francesca; Iughetti, Lorenzo
abstract

Background and aim: Children with heterozygous familial hypercholesterolemia (heFH) are at risk of premature atherosclerosis. Aims of this study were: (a) to longitudinally evaluate the endothelial dysfunction, estimated through brachial flow mediated dilation (FMD), as first sign of subclinical atherogenesis in a group of children and adolescents affected by heFH in comparison to normo-lipidemic controls, and (b) to identify predictive factors influencing the endothelial function and its development in the same cohort of patients. Methods: This is a prospective, longitudinal and cross-sectional study. Physical examination, plasma lipid profile and brachial artery FMD were measured at baseline and after follow-up. Results: At baseline, FMD did not differ between heFH children (n.24, median age 9.71) and controls (n. 24, median age 10.29) (7.67 ± 9.26 vs. 11.18 ± 7.28 %, p 0.09). Nevertheless, during follow-up (median length of lipid-lowering diet 4.52 years), FMD got worse in 54% of heFH subjects and its worsening correlated to the increasing of lowdensity lipoprotein cholesterol (r -0.21, p < 0.05). Moreover, being male (β -0.46, p 0.03), undergoing puberty (β -0.61, p 0.03) and increasing of body mass index standard deviation score (β -0.39, p 0.03) were identified as main independent predictor factors of FMD drop. Conclusions: During the first decades of life, not only hypercholesterolemia, but also clusters of pro-atherogenic conditions and their persistence, could affect the endothelial function and its trend.


2021 - Maternal carriage in late-onset group b streptococcus disease, Italy [Articolo su rivista]
Berardi, A.; Spada, C.; Creti, R.; Auriti, C.; Gambini, L.; Rizzo, V.; Capretti, M.; Laforgia, N.; Papa, I.; Tarocco, A.; Lanzoni, A.; Biasucci, G.; Piccinini, G.; Nardella, G.; Latorre, G.; Merazzi, D.; Travan, L.; Reggiani, M. L. B.; Baroni, L.; Ciccia, M.; Lucaccioni, L.; Iughetti, L.; Lugli, L.
abstract

We retrospectively investigated mother-to-infant transmission of group B Streptococcus (GBS) in 98 cases of lateonset disease reported during 2007-2018 by a network in Italy. Mothers with full assessment of vaginal/rectal carriage tested at prenatal screening (APS) and at time of late onset (ATLO) were included. Thirty-three mothers (33.7%) were never GBS colonized; 65 (66.3%) were vaginal/rectal colonized, of which 36 (36.7%) were persistently colonized. Mothers with vaginal/rectal colonization ATLO had high rates of GBS bacteriuria (33.9%) and positive breast milk culture (27.5%). GBS strains from mother- infant pairs were serotype III and possessed the surface protein antigen Rib. All but 1 strain belonged to clonal complex 17. GBS strains from 4 mother-infant pairs were indistinguishable through pulsed-fi eld gel electrophoresis. At least two thirds of late-onset cases are transmitted from mothers, who often have vaginal/rectal carriage, positive breast milk culture, or GBS bacteriuria, which suggests heavy maternal colonization.


2021 - Minipuberty: Looking Back to Understand Moving Forward [Articolo su rivista]
Lucaccioni, L.; Trevisani, V.; Boncompagni, A.; Marrozzini, L.; Berardi, A.; Iughetti, L.
abstract

Hypothalamic-pituitary-gonadal (HPG) axis activation occurs three times in life: the first is during fetal life, and has a crucial role in sex determination, the second time is during the first postnatal months of life, and the third is with the onset of puberty. These windows of activation recall the three windows of the “Developmental Origin of Health and Disease” (DOHaD) paradigm and may play a substantial role in several aspects of human development, such as growth, behavior, and neurodevelopment. From the second trimester of pregnancy there is a peak in gonadotropin levels, followed by a decrease toward term and complete suppression at birth. This is due to the negative feedback of placental estrogens. Studies have shown that in this prenatal HPG axis activation, gonadotropin levels display a sex-related pattern which plays a crucial role in sex differentiation of internal and external genitalia. Soon after birth, there is a new increase in LH, FSH, and sex hormone concentrations, both in males and females, due to HPG re-activation. This postnatal activation is known as “minipuberty.” The HPG axis activity in infancy demonstrates a pulsatile pattern with hormone levels similar to those of true puberty. We review the studies on the changes of these hormones in infancy and their influence on several aspects of future development, from linear growth to fertility and neurobehavior.


2021 - Natural history of congenital hypothyroidism in the last two decades: what is changing? Experience of a single tertiary Italian paediatric centre [Abstract in Rivista]
Bruzzi, Patrizia; Donini, Valentina; Ciancia, Silvia; Lucaccioni, Laura; Predieri, Barbara; Iughetti, Lorenzo
abstract


2021 - Neuroprem 2: An Italian Study of Neurodevelopmental Outcomes of Very Low Birth Weight Infants [Articolo su rivista]
Lugli, L.; Bedetti, L.; Guidotti, I.; Pugliese, M.; Picciolini, O.; Roversi, M. F.; DellaCasa Muttini, E.; Lucaccioni, L.; Bertoncelli, N.; Ancora, G.; Gargano, G.; Mosca, F.; Sandri, F.; Corvaglia, L. T.; Solinas, A.; Perrone, S.; Stella, M.; Iughetti, L.; Berardi, A.; Ferrari, F.
abstract

Background: Despite the increased survival of preterm newborns worldwide, the risk of neurodevelopmental disabilities remains high. Analyzing the outcomes of the preterm population can identify risk factors and enable specific early interventions. Aims: Neuroprem is a prospective cohort study of very low birth weight (VLBW) infants that aims to evaluate the neurodevelopmental outcomes and risk factors for severe functional disability at 2 years of corrected age. Methods: Nine Italian neonatal intensive care units participated in the network. The Griffiths Mental Developmental Scales (GMDS-R) or the Bayley Scales of Infant and Toddler Development (BSDI III) and a neuro-functional evaluation (according to the International Classification of Disability and Health and Neuro-Functional Assessment, or NFA ICF-CY) were administered to VLBW infants at 24 months of corrected age. The primary outcome measure was severe functional disability, defined as cerebral palsy, bilateral blindness, deafness, an NFA ICF-CY of >2, a BSDI III cognitive composite score of <2 SD, or a GMDS-R global quotient score of <2 SD. Perinatal risk factors for severe functional disability were assessed through multivariate logistic regression analysis. Results: Among 502 VLBW survivors who completed the 24-month follow-up, 48 (9.6%) presented severe functional disability, of whom 27 had cerebral palsy (5.4%). Rates of severe functional disability and cerebral palsy were higher in neonates with a lower gestational age (p < 0.001). Overall, 147 infants (29.3%) were referred to neuromotor intervention. In the multivariate regression model, gestational age at birth OR 0.79; 95% CI 0.67–0.90; p = 0.001) and periventricular-intraventricular hemorrhage (OR 2.51; 95% CI 1.19–5.26; p = 0.015) were significantly associated with severe functional disability. Conclusion: Neuroprem 2 provides updated information on the neurodevelopmental outcomes of VLBW infants in a large Italian cohort. The overall rate of neurodevelopmental disabilities was quite lower than reported in the previous literature. These data indicate the need for structured follow-up programs from a national neonatal network perspective.


2021 - Non-coronary cardiac events, younger age, and IVIG unresponsiveness increase the risk for coronary aneurysms in Italian children with Kawasaki disease [Articolo su rivista]
Fabi, M.; Andreozzi, L.; Frabboni, I.; Dormi, A.; Corinaldesi, E.; Lami, F.; Cicero, C.; Tchana, B.; Francavilla, R.; Sprocati, M.; Bigucci, B.; Balsamo, C.; Valin, P. S.; Di Fazzio, G.; Iughetti, L.; Valletta, E.; Marchetti, F.; Donti, A.; Lanari, M.
abstract

Objectives: Kawasaki disease (KD) is the most frequent cause of acquired heart disease in children in high-income countries because of coronary artery involvement. Risk factors for coronary lesions can vary in consideration of different genetic background and environmental factors. Methods: Multicenter retrospective and prospective study including 372 consecutive children (58% boys; mean age 34.3 ± 30.3 months, Caucasian 85%) was diagnosed with KD. We divided the cohort into 2 groups according to the presence of coronary anomalies (CAA) and aneurysms. We compared the groups and studied the risk factors for CAA and for aneurysms, the most severe lesions. Results: Children with CAA were 91/372 (24.46%, aneurysms 20/372, 5.37%). Children with CAA were more likely to have a longer duration of fever (p < 0.001), later day of treatment (p < 0.001), to be IVIG non-responders and late treated (p < 0.001), while age, clinical presentation, and seasonality were not different. They also had significantly higher WBC and neutrophils, lower lymphocytes, Hb and Na during the acute stage, and slower resolution of inflammation. Age, IVIG unresponsiveness, and presence of non-coronary cardiac findings were independent risk factors for CAA and for aneurysms, while neutrophils just for CAA. Age under 6 months was a risk factor for the aneurysm. Aneurysms occurred more frequently in the first quartile of the age of KD onset (under 14 months). Conclusion: Very young children with non-coronary cardiac findings are at increased risk for a more severe form of KD with aneurysms. These children could benefit from adjunctive therapy beside IVIG, especially if they have higher markers of inflammation, particularly neutrophils.Key points• Risk factors for coronary lesions can vary in consideration of different genetic background and environmental factors.• Risk factors for coronary involvement have been extensively studied in the Asian population, and others have been validated in cohorts with mixed ethnicities.• In our predominantly Caucasian population, non-coronary cardiac findings, age younger than 6 months, and IVIG unresponsiveness are independent risk factors for a more severe form of KD with aneurysms.


2021 - Occhio all’asimmetria toracica alla nascita... e se fosse la sindrome di Poland?. [Articolo su rivista]
Di Caprio, A; Bedetti, L; Madeo, Sf; Lucaccioni, L; Roversi, F; Iughetti, L; Berardi, A.
abstract

Poland syndrome is a rare congenital disorder characterized by agenesis of the pectoralis major muscle. It is usually unilateral and right-sided and can be associated with several thoracic and upper limb defects. Early diagnosis and timely therapeutic approaches play an important role, improving the quality of life of patients and their families. This case report aims to show the benefits of early diagnosis, especially for follow-up management.


2021 - Pediatric inflammatory multisystem disease in children with covid-19-reply [Articolo su rivista]
Iughetti, L.
abstract


2021 - Perinatal exposure to phthalates: From endocrine to neurodevelopment effects [Articolo su rivista]
Lucaccioni, L.; Trevisani, V.; Passini, E.; Righi, B.; Plessi, C.; Predieri, B.; Iughetti, L.
abstract

Phthalates, as other endocrine disrupting chemicals (EDCs), may alter the homeostasis and the action of hormones and signaling molecules, causing adverse health outcomes. This is true especially for infants, who are both more exposed and sensitive to their effects. Phthalates are particularly harmful when the exposure occurs during certain critical temporal windows of the development, such as the prenatal and the early postnatal phases. Phthalates may also interfere with the neuroendocrine systems (e.g., thyroid hormone signaling or metabolism), causing disruption of neuronal differentiation and maturation, increasing the risk of behavioral and cognitive disorders (ADHD and autistic behaviors, reduced mental, psychomotor, and IQ development, and emotional problems). Despite more studies being needed to better understand the role of these substances, plenty of evidence suggests the impact of phthalates on the neuroendocrine system development and function. This review aims to update the knowledge on the neuroendocrine consequences of neonatal and perinatal exposure to phthalates.


2021 - Pituitary Macroadenoma and Severe Hypothyroidism: The Link between Brain Imaging and Thyroid Function [Articolo su rivista]
Ciancia, S; Cesari, S; Predieri, B; Bernasconi, S; Iughetti, L.
abstract

In case of primary hypothyroidism, reactive pituitary hyperplasia can manifest as pituitary (pseudo) macroadenoma. We report the case of a 12-year-old boy who was evaluated for impaired growth velocity and increased body weight. Because of low insulin-like growth factor 1 levels and poor response to the growth hormone stimulation test, brain magnetic resonance imaging was performed and a pituitary macroadenoma was found. Treatment with levothyroxine was started, and thyroid function was evaluated approximately every 40 days to titrate the dosage. After few months of therapy, the size of the macroadenoma decreased and growth hormone secretion normalized. The pituitary returned to normal size in approximately 5 years. The boy went through puberty spontaneously and reached a normal adult height. In a patient affected by primary hypothyroidism, reactive pituitary hyperplasia can cause growth hormone deficiency; however, growth hormone secretion usually normalizes after starting levothyroxine treatment. Pituitary macroadenoma can be difficult to distinguish from severe pituitary hyperplasia; however, pituitary macroadenomas are rare in childhood, and our clinical case underlines how the hormonal evaluation is essential to achieve a correct diagnosis and prevent unnecessary surgery in a context of pituitary mass.


2021 - Pneumococcal septic shock after neonatal respiratory syncytial virus bronchiolitis: A case report and literature review [Articolo su rivista]
Di Caprio, A.; Coccolini, E.; Zagni, P.; Vaccina, E.; Lucaccioni, L.; Lugli, L.; Iughetti, L.; Berardi, A.
abstract

Background: Bronchiolitis is a common cause of hospitalisation of infants less than a year old, with most infants recovering without complications. Respiratory syncytial virus (RSV) is a leading cause of bronchiolitis. Antimicrobial stewardship programmes do not recommend antibiotics for viral infections in neonates unless documented evidence of secondary bacterial infection is present. Case report: We present the case of a 7-day-old infant admitted to hospital with chest retractions and fever. The baby was hospitalised, empirical antibiotic therapy was administered, and non-invasive ventilation was started. When the viral aetiology was identified and clinical conditions improved, antibiotics were discontinued. However, after 48 hours, the newborn’s condition worsened because of pneumococcal septic shock. Intravenous fluids, catecholamine support, and wide-spectrum antibiotics were administered. Non-invasive ventilation was re-started and continued until the full recovery. Conclusions: There is increasing evidence that RSV and S. pneumoniae co-infect and interact with each other, thus increasing respiratory diseases’ severity. We provide a brief overview of the main international guidelines for managing bronchiolitis. Guidelines suggest avoidance of antibiotics use when the diagnosis of viral bronchiolitis is confirmed. We discuss the uncertainties regarding antibiotic use, especially in younger infants, who are more exposed to risks of bacterial superinfection. (www.actabiomedica.it).


2021 - QUALITÀ DI VITA E CONTROLLO METABOLICO NEI BAMBINI ED ADOLESCENTI CON DIABETE DI TIPO 1 E NEI LORO GENITORI PRIMA E DOPO IL LOCKDOWN PER COVID-19. [Abstract in Atti di Convegno]
Predieri, Barbara; Bruzzi, Patrizia; Candia, Francesco; Caccamo, Paola; Sandoni, Marcello; Stefanelli, Francesca; Pugliese, Marisa; Lucaccioni, Laura; Madeo, Simona F.; Iughetti, Lorenzo
abstract


2021 - Retrospective 8-year study on the antibiotic resistance of uropathogens in children hospitalised for urinary tract infection in the emilia-romagna region, italy [Articolo su rivista]
Esposito, S.; Maglietta, G.; Di Costanzo, M.; Ceccoli, M.; Vergine, G.; La Scola, C.; Malaventura, C.; Falcioni, A.; Iacono, A.; Crisafi, A.; Iughetti, L.; Conte, M. L.; Pierantoni, L.; Gatti, C.; Caminiti, C.; Biasucci, G.
abstract

The development and spread of antibiotic resistance is an increasingly important global public health problem, even in paediatric urinary tract infection (UTI). In light of the variability in the data, it is necessary to conduct surveillance studies to determine the prevalence of antibiotic resistance in specific geographical areas to optimize therapeutic management. In this observational, retrospective, multicentre study, the medical records of 1801 paediatric patients who were hospital-ised for UTI between January 1st, 2012, and June 30th, 2020, in Emilia-Romagna, Italy, were analysed. Escherichia coli was the most frequently detected pathogen (75.6%), followed by Klebsiella pneumoniae (6.9%) and Pseudomonas aeruginosa (2.5%). Overall, 840 cases (46.7%) were due to anti-microbial-resistant uropathogens: 83 (4.7%) extended spectrum beta-lactamase (ESBL)-producing, 119 (6.7%) multidrug resistant (MDR) and 4 (0.2%) extensively drug resistant (XDR) bacteria. Empirical antibiotic therapy failed in 172 cases (9.6%). Having ESBL or MDR/XDR uropathogens, a history of recurrent UTI, antibiotic therapy in the preceding 30 days, and empirical treatment with amoxicillin or amoxicillin/clavulanate were significantly associated with treatment failure, whereas first-line therapy with third-generation cephalosporins was associated with protection against negative outcomes. In conclusion, the increase in the resistance of uropathogens to commonly used antibiotics requires continuous monitoring, and recommendations for antibiotic choice need updating. In our epidemiological context, amoxicillin/clavulanate no longer seems to be the appropriate first-line therapy for children hospitalised for UTI, whereas third-generation cephalosporins continue to be useful. To further limit the emergence of resistance, every effort to reduce and ration-alise antibiotic consumption must be implemented.


2021 - Safety and effectiveness of a somatropin biosimilar in children requiring growth hormone treatment: second analysis of the PATRO Children study Italian cohort [Articolo su rivista]
Iughetti, L.; Antoniazzi, F.; Giavoli, C.; Bona, G.; Aversa, T.; Greggio, N. A.; Guazzarotti, L.; Minelli, R.; Perrone, L.; Persani, L.; Pozzobon, G.; Ragusa, L.; Stagi, S.; Tornese, G.; Zecchino, C.; Gallinari, P.; Zouater, H.; Fedeli, P.; Zucchini, S.
abstract

Purpose: To investigate the long-term safety (primary endpoint) and effectiveness (secondary endpoint) of the somatropin biosimilar Omnitrope®. Methods: PATRO Children is an ongoing, multicenter, observational, post-marketing surveillance study. Children who received Omnitrope® for any indication were included. Adverse events (AEs) were evaluated in all study participants. Auxological data, including height standard deviation scores (HSDS) and height velocity standard deviation scores (HVSDS), were used to assess effectiveness. In this snapshot analysis, data from the Italian subpopulation up to August 2017 were reported. Results: A total of 291 patients (mean age 10.0 years, 56.0% male) were enrolled at 19 sites in Italy. The mean duration of Omnitrope® treatment was 33.1 ± 21.7 months. There were 48 AEs with a suspected relationship to the study drug (as reported by the investigator) that occurred in 35 (12.0%) patients, most commonly headache, pyrexia, arthralgia, insulin-like growth factor above normal range, abdominal pain, pain in extremity and acute gastroenteritis. There were no confirmed cases of type 1 or type 2 diabetes; however, two patients (0.7%) had impaired glucose tolerance that was considered Omnitrope® related. The mean HSDS increased from − 2.41 ± 0.73 at baseline (n = 238) to − 0.91 ± 0.68 at 6.5 years (n = 10). The mean HVSDS increased from − 1.77 ± 1.38 at baseline (n = 136) to 0.96 ± 1.13 at 6.5 years (n = 10). Conclusions: In this sub-analysis of PATRO Children, Omnitrope® appeared to have acceptable safety and effectiveness in the treatment of in Italian children, which was consistent with the earlier findings from controlled clinical trials.


2021 - Safety and Success of Lumbar Puncture in Young Infants: A Prospective Observational Study [Articolo su rivista]
Bedetti, L.; Lugli, L.; Marrozzini, L.; Baraldi, A.; Leone, F.; Baroni, L.; Lucaccioni, L.; Rossi, C.; Roversi, M. F.; D'Amico, R.; Iughetti, L.; Berardi, A.
abstract

Objective: This study aims to evaluate safety and success rates of lumbar puncture (LP) and to identify factors associated with adverse events or failure of LP in infants. Methods: This two-center prospective observational study investigated infants younger than 90 days of age who underwent LP. Need for resuscitation oxygen desaturation (SpO2 < 90%), bradycardia and intraventricular hemorrhage were considered adverse events. LP failed if cerebrospinal spinal fluid was not collected or had traces of blood. Logistic regression analysis was used to evaluate whether corrected gestational age (GA), body weight at LP, position, and any respiratory support during LP affected SpO2 desaturation or failure of LP. Results: Among 204 LPs, 134 were performed in full-term and 70 in pre-term born infants. SpO2 desaturations occurred during 45 (22.4%) LPs. At multivariate analysis, lower GA at LP (p < 0.001), non-invasive respiratory support (p 0.007) and mechanical ventilation (p 0.004) were associated with SpO2 desaturations. Transient, self-resolving bradycardia occurred in 7 (3.4%) infants. Two infants had intraventricular hemorrhage detected within 72 h of LP. No further adverse events were registered. Failure of LP occurred in 38.2% of cases and was not associated with any of the factors evaluated. Conclusions: LP was safe in most infants. Body weight or GA at LP did not affect LP failure. These data are useful to clinicians, providing information on the safety of the procedure.


2021 - SEPTIC SHOCK in the FIRST THREE MONTHS of LIFE [Articolo su rivista]
Crestani, S.; Passini, E.; Spaggiari, V.; Toffoli, C.; Boncompagni, A.; Bedetti, L.; Spaggiari, E.; Lucaccioni, L.; Lugli, L.; Roversi, F.; Rossi, K.; Iughetti, L.; Berardi, A.
abstract

Shock is a generalized tissue hypoperfusion that leads to severe cellular distress and complicates some cases of paediatric and neonatal sepsis. Although a reduction in associated sepsis mortality has been observed in the last decades, it remains one of the most important causes of death or long-term neurodevelopmental disabilities in children. Prompt recognition of this condition is therefore essential to improve survival and long-term outcome. The paediatrician and the neonatologist must therefore be able to promptly recognize the signs and symptoms of sepsis and septic shock to set up an adequate treatment according to the most recent international guidelines. This article provides epidemiological data from Italian and international studies, describes the pathophysiology and clinical manifestations of sepsis and septic shock, as well as the therapeutic indications according to very recent recommendations.


2021 - Si può “Valere” di più: un progetto italiano studia i disturbi alimentari negli adolescenti con diabete tipo 1. Dati preliminari [Abstract in Atti di Convegno]
Troncone, Alda; Iafusco, Dario; Curto, Stefano; Piscopo, Alessia; Zanfardino, Angela; Cascella, Crescenzo; Affuso, Gaetana; Chianese, Antonietta; Lera, Liccardo; Patrizia Bracciolini, Giulia; Grosso, Caterina; Bertelli, Giulia; Cherubini, Valentino; Piccinno, Elvira; Delvecchio, Maurizio; Ortolani, Federica; Vendemiale, Marcella; Rutigliano, Alessandra; Zecchino, Clara; Zucchini, Stefano; Maltoni, Giulio; Scarponi, Dorella; Fraternale, Lucia; Susanna Coccioli, Maria; Brugnola, Vito; Gallo, Francesco; Ripoli, Carlo; Rossella Ricciardi, Maria; Pascarella, Filomena; Perrotti, Arcangelo; Golino, Anna; Stamati, Filomena; Caruso Nicoletti, Manuela; Lo Presti, Donatella; Saggio, Annalisa; Citriniti, Felice; Sperlì, Domenico; De Marco, Rosaria; Daniela Borselli, Maria; Lazzaro, Nicola; Toni, Sonia; Balbo, Verena; D’Annunzio, Giuseppe; Minuto, Nicola; Parodi, Alice; Caloiero, Mimma; Aloe, Monica; Corsini, Maria; Lombardo, Fortunato; Pecoraro, Danila; Bonfanti, Riccardo; Pozzi, Clara; Iughetti, Lorenzo; Predieri, Barbara; Pugliese, Marisa; Rabbone, Ivana; Pignatiello, Ciro; Galderisi, Alfonso; Santoro, Giacomo; De Berardinis, Fiorella; Iovane, Brunella; Dioni, Silvia; Carmela Lia, Maria; Tutino, Rita; Cianfarani, Stefano; Schiaffini, Riccardo; Patrizia Patera, Ippolita; Cristina Matteoli, Maria; Carducci, Chiara; Rutigliano, Irene; Franca Minenna, Adelaide; Trada, Michela; Tinti, Davide; Montarulo, Cinzia; Cardinale, Giuliana; de Leo, Sofia; Arnaldi, Claudia; Longo, Barbara
abstract


2021 - Spectrum of Cardiovascular Diseases in Children during High Peak Coronavirus Disease 2019 Period Infection in Northern Italy: Is There a Link? [Articolo su rivista]
Fabi, M.; Filice, E.; Andreozzi, L.; Conti, F.; Gabrielli, L.; Balducci, A.; Vergine, G.; Cicero, C.; Iughetti, L.; Guerzoni, M. E.; Corinaldesi, E.; Lazzarotto, T.; Pession, A.; Lanari, M.
abstract

Background:Children with coronavirus disease-2019 (COVID-19) have a milder clinical course than adults. We describe the spectrum of cardiovascular manifestations during a COVID-19 outbreak in Emilia-Romagna, Italy. Methods:A cross-sectional multicenter study was performed, including all patients diagnosed with Kawasaki disease (KD), myocarditis, and multisystem inflammatory syndrome in children (MIS-C) from February to April 2020. KD patients were compared with those diagnosed before the epidemic. Results:KD: 8 patients (6/8 boys, all negative for severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2]): complete presentation in 5/8, 7/8 immunoglobulin (IVIG) responders, and 3/8 showed transient coronary lesions (CALs). Myocarditis: one 5-year-old girl negative for SARS-CoV-2 and positive for parvovirus B19. She responded to IVIG. MIS-C: 4 SARS-CoV-2-positive boys (3 patients with positive swab and serology and 1 patient with negative swab and positive serology): 3 presented myocardial dysfunction and pericardial effusion, and 1 developed multicoronary aneurysms and hyperinflammation; all responded to treatment. The fourth boy had mitral and aortic regurgitation that rapidly regressed after steroids. Conclusions:KD, myocarditis, and MIS-C were distinguishable cardiovascular manifestations. KD did not show a more aggressive form compared with previous years: coronary involvement was frequent but always transient. MIS-C and myocarditis rapidly responded to treatment without cardiac sequelae despite high markers of myocardial injury at the onset, suggesting a myocardial depression due to systemic inflammation rather than focal necrosis. Evidence of actual or previous SARS-CoV-2 infection was documented only in patients with MIS-C.


2021 - Stimulated GH levels during the transition phase in Prader–Willi syndrome [Articolo su rivista]
Grugni, G.; Marzullo, P.; Delvecchio, M.; Iughetti, L.; Licenziati, M. R.; Osimani, S.; Ragusa, L.; Salvatoni, A.; Sartorio, A.; Stagi, S.; Crino, A.
abstract

Purpose: Early institution of GH therapy in children with Prader–Willi syndrome (PWS) yields beneficial effects on their phenotype and is associated with a persistent improvement of body composition, both in the transition age and in adulthood. Reports from GH stimulation testing in PWS adults, however, suggest that GH deficiency (GHD) is not a universal feature of the syndrome, and the current Consensus Guidelines suggest to perform a reassessment of persistent GHD so as to continue GH therapy after reaching adult height. Few data about GH responsiveness to stimulation testing throughout the transitional period in PWS are available to date. Thus, we investigated the prevalence of GHD in a large cohort of patients with PWS during the transition phase. Patients and methods: One hundred forty-one PWS patients, 72 females and 69 males, aged 15.4–24.9 years, were evaluated by dynamic testing with growth hormone‐releasing hormone (GHRH) plus arginine (GHRH + ARG). To define GHD, both BMI-dependent and BMI-independent diagnostic cut-off limits were considered. Results: According to BMI‐dependent criteria, 10.7% of normal weight (NW), 18.5% of overweight and 22.1% of obese PWS maintained a status of GHD. Similar results were obtained by adopting a cut-off limit specific for the adult age (26.2%), as well as criteria for the transition phase in NW subjects (25%). Conclusion: Our study shows that about 20% of patients with PWS fulfilled the criteria for GHD during the transitional age, suggesting the need of an integrated analysis of GH/IGF-I axis, in the context of the general clinical picture and other endocrine abnormalities, in all subjects after attainment of final stature.


2021 - Storia naturale dell’ipotiroidismo congenito: cosa è cambiato negli ultimi vent’anni? [Abstract in Atti di Convegno]
Bruzzi, Patrizia; Ciancia, Silvia; Donini, Valentina; Lucaccioni, Laura; Madeo, Simona Filomena; Predieri, Barbara; Iughetti, Lorenzo
abstract


2021 - The discharge of children with medical complexity: an 11-year study in an italian neonatal intensive care unit [Articolo su rivista]
Lugli, L.; Garetti, E.; Rossi, K.; Torcetta, F.; Cuomo, G.; Lucaccioni, L.; Pugliese, M.; Bertoncelli, N.; Rossi, C.; Riva, M.; Iughetti, L.; Ferrari, F.; Berardi, A.
abstract

Background - In the last few years care for children with severe chronic conditions is a topic of increasing interest. Children with chronic illness often require a high complexity of care and a high level of coordination among health services. Objective - The primary aim of this study is the assessment of children with chronic disease and high complexity of care (children with medical complexity), discharged from the Neonatal Intensive Care Unit (NICU) of Modena University-Hospital. The secondary aim is to assess the outcome of these patients. Methods - Patients with chronic diseases and high complexity of care (children with medical complexity), aged 0-6 months, and admitted to the NICU of Modena in the years 2009-2019 were recruited. Results - 59 subjects were included, of which 15 (25.4%) were born preterm, 11 (18.6%) suffered from hypoxic-ischemic encephalopathy, 33 (56%) had genetic diseases or malformations. All patients were discharged home, except for one patient who was discharged to hospice. The average hospital length of stay was 116.0 ± 63.4 days. Follow-up visits showed that 25 cases (42.4%) remained unchanged, 18 (30.5%) improved and 16 (27.1%) died. Conclusion - This study allows an assessment of patients with early diagnosis of chronic disease with high complexity of care, showing that some of these patients could be eligible for palliative care. The management of children with medical complexity requires diagnostic-therapeutic programmes that focus on them and their families and connect hospital and territorial health services.


2021 - The miRNA network and the interplay between growth and cancer regulating pathways in prepubertal patients with idiopathic isolated growth hormone deficiency (IGHD) on growth hormone (GH) treatment [Abstract in Rivista]
Catellani, Cecilia; Ravegnini, Gloria; Sartori, Chiara; Righi, Beatrice; Poluzzi, Silvia; Predieri, Barbara; Iughetti, Lorenzo; Angelini, Sabrina; Elisabeth Street, Maria
abstract


2021 - The ontogeny of limbs movements towards midline in healthy infants born at term [Articolo su rivista]
Lucaccioni, Laura; Bertoncelli, Natascia; Comini, Martina; Martignoni, Laura; Coscia, Alessandra; Lugli, Licia; Righi, Elena; Iughetti, Lorenzo; Berardi, Alberto; Ferrari, Fabrizio
abstract

Background: Movements towards midline are part of the age-adequate motor repertoire of infants. They develop contemporaneously to general movements, changing from occasional simple contact to proper midline motor patterns. Aim: The aim of this study is to describe the ontogeny of movements towards midline in full term healthy infants. Study design:Parents were asked to record their infant every second week, from term age to 22 weeks post-term. Subjects:25 healthy full-term infants. Result: Three main epochs of development were detected: in the first one, between birth and 4 weeks post-term, movements towards midline were occasional, apparently due to the dominant flexed posture of elbow and knees and the adducted posture of shoulders and hips. In the second epoch, from 4 to 8 weeks, the limbs movements towards midline markedly decreased. In the third one, after 8 weeks, movements towards midline increased again in frequency, first appearing in lower limbs then in upper limbs, first solely as contact and thereafter as manipulation. A temporal overlapping with the occurrence of intermittent or continual fidgety movements was detected. Conclusions: Movements towards midline progressively change, through a defined timeline, in full term healthy infants. The increased knowledge about the normal age-adequate motor repertoire can help physicians in clinical assessment of high risk infants.


2021 - Understanding factors in group b streptococcus late-onset disease [Articolo su rivista]
Berardi, A.; Trevisani, V.; Di Caprio, A.; Bua, J.; China, M.; Perrone, B.; Pagano, R.; Lucaccioni, L.; Fanaro, S.; Iughetti, L.; Lugli, L.; Creti, R.
abstract

Group B streptococcus (GBS) infection remains a leading cause of sepsis, pneumonia, and meningitis in infants. Rates of GBS early onset disease have declined following the widcespread use of intrapartum antibiotic prophylaxis; hence, late-onset infections (LOGBS) are currently a common presentation of neonatal GBS dicsease. The pathogenesis, mode of transmission, and risk factors associated with LOGBS are unclear, which interfere with effective prevention efforts. GBS may be transmitted from the mother to the infant at the time of delivery or during the postpartum period via contaminated breast milk, or as nosocomial or community-acquired infection. Maternal GBS colonization, pre-maturity, young maternal age, HIV exposure, and ethnicity (Black) are identified as risk factors for LOGBS disease; however, further studies are necessary to confirm additional risk factors, if any, for the implementation of effective prevention strategies. This narrative review discusses current and previous studies that have reported LOGBS. Few well-designed studies have described this condition; therefore, reliable assessment of maternal GBS colonization, breastfeeding, and twin delivery as risk factors for LOGBS remains limited.


2021 - Use of monoclonal antibody to treat covid-19 in children and adolescents: Risk of abuse of prescription and exacerbation of health inequalities [Articolo su rivista]
Esposito, S.; Zona, S.; Pession, A.; Iughetti, L.; Migliori, G. B.; Principi, N.
abstract

Monoclonal antibodies (mAbs) that neutralize SARS-CoV-2 in infected patients are a new class of antiviral agents approved as a type of passive immunotherapy. They should be administered to adults and children (≥12 years old, weighing ≥ 40 kg) with SARS-CoV-2 positivity, and who are suffering from a chronic underlying disease and are at risk of severe COVID-19 and/or hospitalization. The aim of this manuscript is to discuss the benefit-to-risk of mAb therapy to treat COVID-19 in pediatric age, according to current reports. A problem is that the authorization for mAbs use in children was given without studies previously evaluating the efficacy, safety and tolerability of mAbs in pediatric patients. Moreover, although the total number of children with chronic severe underlying disease is not marginal, the risk of severe COVID-19 in pediatric age is significantly reduced than in adults and the role of chronic underlying disease as a risk factor of severe COVID-19 development in pediatric patients is far from being precisely defined. In addition, criteria presently suggested for use of mAbs in children and adolescents are very broad and may cause individual clinicians or institutions to recommend these agents on a case-by-case basis, with an abuse in mAbs prescriptions and an exacerbation of health inequalities while resources are scarce. Several questions need to be addressed before their routine use in clinical practice, including what is their associated benefit-torisk ratio in children and adolescents, who are the patients that could really have benefit from their use, and if there is any interference of mAb therapy on recommended vaccines. While we wait for answers to these questions from well-conducted research, an effective and safe COVID-19 vaccine for vulnerable pediatric patients remains the best strategy to prevent COVID-19 and represents the priority for public health policies.


2021 - Usefulness of serological antibodies assays to better evaluate the prevalence of SARS-CoV-2 infection in youths with type 1 diabetes [Abstract in Rivista]
Predieri, B.; Bruzzi, P.; Meacci, M.; Caccamo, P.; Di Caprio, A.; Trevisani, V.; Iughetti, L.
abstract

Introduction: In youths with type 1 diabetes (T1D), diabetic ketoacidosis (DKA) at onset increased during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. In adults, diabetes was identified as risk factor for severe symptoms and hospitalization with the coronavirus disease-2019 (COVID-19) Objectives: To investigate the prevalence of SARS-CoV-2 infection and clinical characteristics of COVID-19 in children and adolescents with T1D Methods: SARS-CoV-2 infection was defined according to selfreported SARS-CoV-2 nasal swab PCR results (n=210) during the pandemic and seroprevalence of SARS-CoV-2 antibodies (n=85) from Jan to Jun-21. SARS-CoV-2 IgG were assessed using a chemiluminescent immunoassay (CLIA). Clinical characteristics and glycemic control data were collected before (T0) and 3-months after (T1) infection Results: SARS-CoV-2 infection was detected in 39 patients [24 males; median age 13.5 yrs (4.74-19.8); T1D duration 5.49 yrs (0.27-12.6)]: 26 (66.6%) based on positive nasal swab PCR and 13 (33.4%) on positive SARS-CoV-2 IgG. Patients detected by CLIA were asymptomatic. Four patients detected by nasal swab PCR were asymptomatic (15.4%), while the others reported ≥1 symptoms lasting a median of 5 days: fever (46.1%), headache (28.2%), anosmia and/or ageusia (25.6%), nasal congestion (15.4%), fatigue/myalgia (10.2%). Dry cough, pharyngeal erythema, nausea/vomiting, diarrhea, abdominal pain, arthralgia were reported by 2.56%. Glycemic control was not impaired from T0 to T1 (median HbA1c 58.5 vs 57.4 mmol/mol; TIR 58.5 vs 56.5%). Hospitalization and DKA were not recorded Conclusions: Using seroprevalence of antibodies we found an increased prevalence of SARS-CoV-2 infection that had no impact on glycemic control and acute complications. Asymptomatic subjects were 43%, while fever, headache, anosmia/ageusia were the most common clinical characteristics. Our data suggest that serological assay is useful to diagnosing previous SARS-CoV-2 infection and could be used to reconstruct the disease prevalence.


2021 - Uso delle gonadotropine urinarie per la valutazione del profilo minipuberale in neonati e lattanti di sesso maschile [Abstract in Atti di Convegno]
Lucaccioni, Laura; Trevisani, Viola; Righi, Beatrice; Passini, Erica; Di Caprio, Antonella; Bruzzi, Patrizia; Madeo, Simona Filomena; Predieri, Barbara; Righi, Elena; Iughetti, Lorenzo
abstract


2020 - Changes of intestinal microbiota in early life [Articolo su rivista]
Ficara, Monica; Pietrella, Elisa; Spada, Caterina; Casa Muttini Elisa, Della; Lucaccioni, Laura; Iughetti, Lorenzo; Berardi, Alberto
abstract

There is increasing evidence that the intestinal microbiota plays a pivotal role in the maturation of the immune system and in the prevention of diseases occurring during the neonatal period, childhood and adulthood. A number of nonphysiological conditions during the perinatal period (ie caesarean section, prolonged hospitalization, formula feeding, low gestational age) may negatively affect the normal development of the microbiota, leading to decreased amounts of lactobacilli and bifidobacteria and increased amounts of Clostridia . In addition, perinatal antibiotics can cause intestinal dysbiosis that has been associated with short- and long-term diseases. For example, prolonged early empiric antibiotics increase the risk of necrotizing enterocolitis and late-onset sepsis in preterm neonates, whereas the administration of intrapartum antibiotic prophylaxis has been associated with inflammatory bowel diseases, obesity and atopic conditions, such as eczema and wheezing. Promoting breastfeeding, reducing the length of hospital stay, and reducing unnecessary antibiotic therapies are useful strategies to counterbalance unintended effects of these conditions.


2020 - Children with special health care needs attending emergency department in Italy: analysis of 3479 cases [Articolo su rivista]
Cianci, P.; D'Apolito, V.; Moretti, A.; Barbagallo, M.; Paci, S.; Carbone, M. T.; Lubrano, R.; Urbino, A.; Dionisi Vici, C.; Memo, L.; Zampino, G.; La Marca, G.; Villani, A.; Corsello, G.; Selicorni, A.; Campania, A.; Geremia, C.; Urbino, A.; Castagno, E.; Masi, S.; Poggi, G.; Vestri, M.; Fossali, E.; Rocchi, A.; Dadalt, L.; Arrighini, A.; Chiappa, S.; Renna, S.; Piccotti, E.; Borgna, C.; Govoni, M. R.; Biondi, A.; Fossati, C.; Iughetti, L.; Bertolani, P.; Salvatoni, A.; Agosti, M.; Fuca, F.; Ilardi, A.; Giuffrida, S.; Diguardo, V.; Memo, L.; Boni, S.; D'Antiga, L.; Ruggeri, M.; Chiaretti, A.; Zampino, G.; Amarri, S.; Peduto, A.; Bernardi, F.; Corsini, I.; Deangelis, G. L.; Ruberto, C.; Zuccotti, G. V.; Stringhi, C.; Lombardi, G.; Salladini, C.; Dimichele, S.; Parola, L.; Porta, A.; Biasucci, G.; Bellini, M.; Ortisi, M. T.; Apuril, E.; Midulla, F.; Tarani, L.; Parlapiano, G.; Lietti, D.; Sforzini, C.; Marseglia, G. L.; Savasta, S.; Falsaperla, R.; Vitaliti, M. C.; Chiarelli, F.; Rossi, N.; Banderali, G.; Giacchero, R.; Bernardo, L.; Pinto, F.; Fabiani, E.; Ficcadenti, A.; Pellegrini, G.; Giacoma, S.; Biban, P.; Spada, S.; Tipo, V.; Carbone, M. T.; Ghitti, C.; Bolognini, S.; Mariani, G.; Russo, A.; Colella, M. G.; Verrico, A.; Bruni, P.; Poddighe, D.; Cagnoli, G.; Morandi, F.; Gadaleta, A.; Barbi, E.; Bruno, I. I.; Graziano, R.; Sgaramella, P.; Catalani, M. P.; Baldoni, I.; Colarusso, G.; Galvagno, G.; Barone, A. P.; Longo, A.; Nardella, G.; Portale, G.; Garigali, G.; Bona, G.; Erbela, M.; Agostiniani, R.; Nanni, L.; Schieven, E.; Dona, M.; Varisco, T.; Russo, F.; Distefano, V. A.; Dipietro, F.; Tarallo, L.; Imperato, L.; Parisi, G.; Salzano, R.; Raiola, G.; Talarico, V.; Bellu, R.; Cannone, A.; Ferrante, P.
abstract

Background: Although children with special health care needs (CSHCN) represent a minority of the population, they go through more hospitalizations, more admissions to the Emergency Department (ED), and receive a major number of medical prescriptions, in comparison to general pediatric population. Objectives of the study were to determine the reasons for admission to the ED in Italian CSHCN, and to describe the association between patient’s demographic data, clinical history, and health services requirements. Methods: Ad hoc web site was created to collect retrospective data of 3479 visits of CSHCN to the ED in 58 Italian Hospitals. Results: Seventy-two percent of patients admitted to ED were affected by a previously defined medical condition. Most of the ED admissions were children with syndromic conditions (54%). 44.2% of the ED admissions were registered during the night-time and/or at the weekends. The hospitalization rate was of 45.6% among patients admitted to the ED. The most common reason for admission to the ED was the presence of respiratory symptoms (26.6%), followed by gastrointestinal problems (21.3%) and neurological disorders (18.2%). 51.4% of the access were classified as ‘urgent’, with a red/yellow triage code. Considering the type of ED, 61.9% of the visits were conducted at the Pediatric EDs (PedEDs), 33.5% at the Functional EDs (FunEDs) and 4.6% at the Dedicated EDs (DedEDs). Patients with more complex clinical presentation were more likely to be evaluated at the PedEDs. CSHCN underwent to a higher number of medical procedures at the PedEDs, more in comparison to other EDs. Children with medical devices were directed to a PedED quite exclusively when in need for medical attention. Subjects under multiple anti-epileptic drug therapy attended to PedEDs or FunEDs generally. Patients affected by metabolic diseases were more likely to look for medical attention at FunEDs. Syndromic patients mostly required medical attention at the DedEDs. Conclusions: Access of CSHCN to an ED is not infrequent. For this reason, it is fundamental for pediatricians working in any kind of ED to increase their general knowledge about CHSCN and to gain expertise in the management of such patients and their related medical complexity.


2020 - Clinical expression of endocrine disruptors in children [Articolo su rivista]
Iughetti, Lorenzo; Lucaccioni, Laura; Street, Maria E; Bernasconi, Sergio
abstract

Health status is the result of complex interaction between individual factors, general environmental factors and specific factors as nutrition or the presence of chemicals. Aim of this review is to point out the more recent knowledge covering the role of the endocrine disrupting chemical (EDC) on pediatric population wellbeing.


2020 - Clinical utility of urinary gonadotrophins in hypergonadotrophic states as Turner syndrome [Articolo su rivista]
Boncompagni, A.; Mcneilly, J.; Murtaza, M.; Lucaccioni, L.; Iughetti, L.; Wong, S. C.; Mason, A.
abstract

Girls with Turner syndrome (TS) are at an increased risk of primary ovarian insufficiency (POI). Good correlation between serum and urinary gonadotrophins exists in children assessed for disorders of puberty, but there is little evidence of their reliability in hypergonadotropic states. To determine whether there was a correlation between serum and urinary Luteinising Hormone (uLH) and Follicle-Stimulating Hormone (uFSH) in hypergonadotrophic states, and whether uFSH could suggest an ovarian failure in TS as Anti-Mullerian Hormone (AMH). Retrospective cohort study of 37 TS girls attending the paediatric TS clinic in Glasgow between February 2015 and January 2019, in whom 96 non-timed spot urine samples were available with a median age at time of sample of 12.89 years (3.07-20.2 years). uLH and uFSH were measured by chemiluminescent microparticle immunoassay. Simultaneous serum gonadotrophins and AMH were available in 30 and 26 girls, respectively. AMH <4 pmol/L was considered indicative of ovarian failure. A strong correlation was found between serum LH and uLH (r 0.860, P<0.001) and serum FSH and uFSH (r 0.905, p<0.001). Among patients≥10 years not on oestrogen replacement, ROC curve identified uFSH as a reasonable marker for AMH<4 pmol/L uFSH of >10.85 U/L indicates an AMH <4 pmol/L with 75% sensitivity and 100 % specificity (AUC 0.875)with similar ability as serum FSH (AUC 0.906). uLH and uFSH are non-invasive, useful and reliable markers of ovarian activity in hypergonadotropic states as TS. uFSH could provide an alternative to AMH (in centres which are limited by availability or cost) in revealing ovarian failure and requirement for oestrogen replacement in pubertal induction.


2020 - COVID-19 and Type 1 Diabetes: Concerns and Challenges [Articolo su rivista]
Trevisani, Viola; Bruzzi, Patrizia; Madeo, Simona; Cattini, Umberto; Lucaccioni, Laura; Predieri, Barbara; Iughetti, Lorenzo
abstract

Due to the current COVID-19 pandemic, worldwide population's lifestyle has changed dramatically, causing psychosocialconsequences. Patients presenting a preexisting chronic condition, as Type 1 Diabetes (T1D), are the ones suffering the most from this situation. Moreover, people affected by diabetes are the ones with the worst prognosis, if infected by SARS-CoV-2. We analyzed why patients with T1D were poorly represented between the subjects hospitalized for COVID-19 and why the cases of diabetic ketoacidosis (DKA) were fewerand more severe compared with the past years. Furthermore, literature has showed howpatients of all ages with T1D did not experience a deterioration in their glucose control throughout the lockdown. Among other causes, this is also due tothe surging use of telemedicine. Finally, we tried to understand how the coronavirus tropism for endocrine tissues could influence the future epidemiology of T1D, focusing on the effects they have on pancreatic beta-cells.


2020 - Diabetic ketoacidosis at the onset of disease during a national awareness campaign: a 2-year observational study in children aged 0-18 years [Articolo su rivista]
Rabbone, Ivana; Maltoni, Giulio; Tinti, Davide; Zucchini, Stefano; Cherubini, Valentini; Bonfanti, Riccardo; Scaramuzza, Andrea; Study Group of the Italian Society for Pediatric Endocrinology and Diabetology (ISPED) (Riccardo Lera, Diabetes; Bobbio, Adriana; Piccinno, Elvira; Reinstadler, Petra; Felappi, Barbara; Prandi, Elena; Gallo, Francesco; Paola Frongia, Anna; Ripoli, Carlo; Lo Presti, Donatella; Tomaselli, Letizia; Cardinale, Giuliana; Andreina Stamati, Filomena; Citriniti, Felice; Suprani, Tosca; Graziani, Vanna; De Berardinis, Fiorella; Zampolli, Maria; De Marco, Rosaria; Cavalli, Claudio; Lazzaro, Nicola; De Donno, Valeria; Toni, Sonia; Piccini, Barbara; Lenzi, Lorenzo; Mainetti, Benedetta; Susanna Coccioli, Maria; D’Annunzio, Giuseppe; Minuto, Nicola; Aloe, Monica; Lucchesi, Sonia; Cirillo, Dante; Sordelli, Silvia; Delvecchio, Maurizio; Lombardo, Fortunato; Salzano, Giuseppina; Meschi, Franco; Iughetti, Lorenzo; Predieri, Barbara; Franzese, Adriana; Mozzillo, Enza; Iafusco, Dario; Cadario, Francesco; Savastio, Silvia; Piredda, G; Cardella, Francesca; Iovane, Brunella; Calcaterra, Valeria; Giulia Berioli, Maria; Biagioni, Martina; Randazzo, Emioli; Patrizia Patera, Ippolita; Schiaffini, Riccardo; Rutigliano, Irene; Lasagni, Anna; Innaurato, Silvia; Gaiero, Alberto; Fichera, Grazziella; Trada, Michela; Guerraggio, Lucia; Cauvin, Vittoria; Franceschi, Roberto; Tornese, Gianluca; Salvatoni, Alessandro; Marigliano, Marco; Sabbion, Alberto; Maffeis, Claudio; Arnaldi., Claudia
abstract

Objective After a previous survey on the incidence of diabetic ketoacidosis (DKA) at onset of type 1 diabetes in children in 2013–2014 in Italy, we aimed to verify a possible decline in the incidence of DKA at onset during a national prevention campaign. Design Prospective observational study. Setting Multicentre study throughout Italy. Intervention National awareness campaign started in November 2015 and held until December 2017. Patients During 2016 and 2017 we collected data on all patients aged 0–18 years with new-onset diabetes. Main outcome measures DKA (pH <7.30), severe DKA (pH <7.1), DKA in children below 6 years and DKA treatment according to the Italian Society for Pediatric Endocrinology and Diabetology (ISPED) protocol were evaluated. Results Records (n=2361) of children with newly diagnosed type 1 diabetes were collected from 58 out of 68 (85.3%) centres of the original survey participants and 100% of the previously surveyed tertiary centres. Overall, DKA was observed in 1124 patients, with an increased rate when compared with the previous survey (47.6% vs 38.5%, p=0.002), and severe DKA in 15.3%. In children below 6 years, DKA was observed in 323 out of 617 (52.5%) and severe DKA in 16.7%; in this age group, occurrence of DKA reduced by 21.3% (p=0.009). DKA treatment according to the ISPED guidelines was adopted in 95% of the centres, with a 27% improvement (p=0.025). Conclusions During a 2-year awareness campaign, DKA at onset of diabetes in children and adolescents 0–18 years is still common and increased when compared with the 2013–2014 survey.


2020 - Dolore addominale acuto nelle adolescenti: le principali patologie di natura ginecologica [Articolo su rivista]
Ciancia, S; Predieri, B; Filareto, I; Iughetti, L
abstract

Abdominal pain in female teenagers can hide a challenging diagnosis because it is essential to consider, together with the more common causes of abdominal pain, the group of conditions of gynecological origin. Some of conditions described in this article show a correlation with menarche and menstrual cycle; conversely, other conditions can be the consequence of the premature and unaware start of sexual activity. Collection of medical history is a major milestone through the achievement of a correct diagnosis and requires peculiar ability of communication, considering the topics and the age of the patient.


2020 - Effetti degli interferenti endocrini su crescita e sviluppo puberale [Articolo su rivista]
Iughetti, Lorenzo; Lucaccioni, Laura; Bernasconi, Sergio; Predieri, Barbara
abstract

Endocrine disruptors are chemicals present in many areas and materials of the common life, from plastics to detergents, from the air we breathe to the food we eat. Their effect on human health is now known and irrefutable. In fact, several epidemiological studies have identified how endocrine disruptors can act on pre- and postnatal growth, thyroid function, glucose metabolism and obesity, puberty, fertility and carcinogenesis, mainly through epigenetic action mechanisms. The activity of endocrine disruptors occurs mainly during the so-called “window periods”:phases of the child’s life particularly susceptible to epigenetic changes, due to the speed of the accretive processes. Among these periods certainly pre- and postnatal life and the period of puberty stand out, strongly influenced from the point of view of DNA methylation processes.


2020 - Encephalitis due to herpes zoster without rash in an immunocompetent 12-year-old girl: Case report and review of the literature [Articolo su rivista]
Ciancia, S.; Crisafi, A.; Fontana, I.; De Fanti, A.; Amarri, S.; Iughetti, L.
abstract

Background: Neurological complications due to reactivation of varicella-zoster virus (VZV) are very uncommon in immunocompetent patients. Generally a vesicular rash is present on one or more dermatomes, preceding or following the main manifestation. Few cases are reported in the international literature, but they concern mainly adult or elderly patients. Case presentation: A 12-year-old girl was referred to our hospital for persisting headache, cough and rhinitis for six days. After first examination, diagnosis of anterior sinusitis was made by nasal endoscopy. The day after, the girl developed psychotic symptoms and altered mental status. Computed tomography (CT) scan was immediately performed but was unremarkable; lumbar puncture revealed leukocytosis with lymphocytic predominance and cerebrospinal fluid polymerase chain reaction (PCR) detected varicella-zoster virus DNA. The diagnosis of acute VZV encephalitis was made. The patient was promptly treated with acyclovir infused intravenously and her clinical conditions rapidly improved. Tests made did not show any condition of immunosuppression. Conclusions: Although if rare, reactivation of VZV can occur in immunocompetent children and its complications can involve central nervous system. Among these complications, meningitis is more common, but cerebral parenchyma can also be involved leading to a severe medical condition that is defined meningoencephalitis. In rare cases vesicular rash may be absent; therefore high level of suspicion is required even in those patients in which suggestive clinical features are not present to guide the diagnosis. Intravenous acyclovir represents the treatment of choice to obtain a fast clinical response and to prevent the onset of late-term complications.


2020 - Endocrine Disrupting Chemicals and Type 1 Diabetes [Articolo su rivista]
Predieri, Barbara; Bruzzi, Patrizia; Bigi, Elena; Ciancia, Silvia; Madeo, Simona F.; Lucaccioni, Laura; Iughetti, Lorenzo
abstract

Type 1 diabetes (T1D) is the most common chronic metabolic disease in children and adolescents. The etiology of T1D is not fully understood but it seems multifactorial. The genetic background determines the predisposition to develop T1D, while the autoimmune process against -cells seems to be also determined by environmental triggers, such as endocrine disrupting chemicals (EDCs). Environmental EDCs may act throughout dierent temporal windows as single chemical agent or as chemical mixtures. They could aect the development and the function of the immune system or of the beta-cells function, promoting autoimmunity and increasing the susceptibility to autoimmune attack. Human studies evaluating the potential role of exposure to EDCs on the pathogenesis of T1D are few and demonstrated contradictory results. The aim of this narrative review is to summarize experimental and epidemiological studies on the potential role of exposure to EDCs in the development of T1D.We highlight what we know by animals about EDCs’ eects on mechanisms leading to T1D development and progression. Studies evaluating the EDC levels in patients with T1D were also reported. Moreover, we discussed why further studies are needed and how they should be designed to better understand the causal mechanisms and the next prevention interventions.


2020 - Endocrine-disrupting chemicals and their effects during female puberty: A review of current evidence [Articolo su rivista]
Lucaccioni, L.; Trevisani, V.; Marrozzini, L.; Bertoncelli, N.; Predieri, B.; Lugli, L.; Berardi, A.; Iughetti, L.
abstract

Puberty is the process of physical changes between childhood and adulthood during which adolescents reach sexual maturity and become capable of reproduction. It is considered one of the main temporal windows of susceptibility for the influence of the endocrine-disrupting chemicals (EDCs). EDCs may act as single chemical agents or as chemical mixtures; they can be pubertal influencers, accelerating and anticipating the processing of maturation of secondary sexual characteristics. Moreover, recent studies have started to point out how exposure to EDCs during puberty may predispose to breast cancer later in life. In fact, the estrogen-mimicking endocrine disruptors (EEDs) may influence breast tissue development during puberty in two main ways: the first is the action on the proliferation of the breast stromal cells, the second concerns epigenetic mechanisms. The aim of this mini-review was to better highlight what is new and what is not completely known regarding the role of EDCs during puberty.


2020 - Glycemic Control Improvement in Italian Children and Adolescents With Type 1 Diabetes Followed Through Telemedicine During Lockdown Due to the COVID-19 Pandemic [Articolo su rivista]
Predieri, B.; Leo, F.; Candia, F.; Lucaccioni, L.; Madeo, S. F.; Pugliese, M.; Vivaccia, V.; Bruzzi, P.; Iughetti, L.
abstract

Background/Objective: To minimize the wide spread of coronavirus disease (COVID-19) pandemic, Italy was placed in an almost complete lockdown state that forced people to “stay at home”. Aim of this study was to evaluate the effects of lockdown on glycemic control in children and adolescents with type 1 diabetes (T1D) followed through telemedicine. Subjects/Methods: This observational study involved patients with T1D using the real-time continuous glucose monitoring (CGM) Dexcom G6®. Ambulatory glucose profile data from the 3-months before schools closure (November 26, 2019–February 23, 2020; T0) and from the 3-months of consecutive lockdown (February 24–May 18, 2020; T1) were compared. Results: Sixty-two children and adolescents (11.1 ± 4.37 years, 50% males) with T1D (median time disease 3.67 years) were enrolled in the study. Insulin total daily dose was unchanged, while time spent on physical activities was decreased (p<0.0001). Despite the lack of statistical significance, median value of the glucose management indicator decreased from 7.4% to 7.25%. Glucose standard deviation (p<0.0001) and coefficient of variation (p=0.001) improved across the study. Median time in range increased from 60.5% to 63.5% (p=0.008), time above range decreased from 37.3% to 34.1% (p=0.048), and time below range decreased from 1.85% to 1.45% (p=0.001). Conclusions: Overall, in our children and adolescents with T1D glycemic control improved during lockdown. Despite patients were confined to their homes and limited to exercise, our data suggest that the use of real-time CGM, the continuous parental management, and the telemedicine can display beneficial effects on T1D care.


2020 - Grisel’s Syndrome in Children: Two Case Reports and Systematic Review of the Literature [Articolo su rivista]
Pini, Nicole; Ceccoli, Martina; Bergonzini, Patrizia; Iughetti, Lorenzo
abstract

: Background and Objective. Grisel's syndrome is a rare syndrome characterized by nontraumatic rotatory subluxation of the atlantoaxial joint. It usually affects children and typically presents with torticollis after ear, nose, and throat (ENT) surgery or head and neck infections. In the pediatric literature, there is only a small amount of available data; moreover, no systematic review has been previously done with focus on the pediatric population. We report our experience of two cases, and we provide a systematic review on Grisel's syndrome in children in order to offer a deeper insight about its clinical presentation, its current diagnosis, and principles of treatment. Case Reports and Review. We describe two boys of 9 and 8 years old, who developed atlantoaxial subluxation after adenoidectomy. Considering the early diagnosis, a conservative treatment was chosen, with no recurrence and no sequelae at follow-up. We identified 114 case reports, of which 90 describe children, for a total of 171 pediatric patients. Of the 154 cases in which cause was reported, 59.7% presented a head and neck infection and 35.7% had previous head and neck surgery. There is no sex prevalence (49.7% males versus 50.2% females). Mean delay in diagnosis is 33 days. Eight % of the patients had neurological impairment of the 165 cases which mentioned treatment, 96% underwent a conservative treatment, of whom the 8.8% recurred with the need of surgery. As a whole, 12% underwent surgery as a first- or second-line treatment. 3 6% of the patients whose follow-up was reported developed a sequela, minor limitation of neck movement being the most frequent. Conclusion. Grisel's syndrome should be suspected in children with painful unresponsive torticollis following ENT procedures or head and neck inflammation. CT scan with 3D reconstruction is the gold standard for diagnosis, allowing the identification of the subluxation and the classification according to the Fielding-Hawkins grading system. Surgical treatment is indicated in case of high-grade instability or failure of conservative treatment. Review of the literature shows how early diagnosis based on clinical and radiological evaluation is crucial in order to avoid surgical treatment and neurologic sequelae.


2020 - Health-Related Quality of Life and Metabolic Control in Immigrant and Italian Children and Adolescents with Type 1 Diabetes and in their Parents [Articolo su rivista]
Predieri, Barbara; Bruzzi, Patrizia; Bigi, Elena; Boncompagni, Alessandra; Bocchi, Federica; Cenciarelli, Valentina; Madeo, Simona F; Poluzzi, Silvia; Pugliese, Marisa; Toffoli, Carlotta; Lucaccioni, Laura; Iughetti, Lorenzo
abstract

Objective: To determine if the diabetes-specific health-related quality of life (D-HRQOL) of young people with type 1 diabetes (T1D) and their parents is influenced by migrant status. Subjects and methods: One hundred and twenty-five patients (12.4±3.55 years, males 53.6%) with T1D and their parents (102 mothers, 37 fathers) were enrolled and categorized into: Group A (both foreign parents) and Group B (both native Italian parents). The Pediatric Quality of Life Inventory™ 3.0 Diabetes Module (PedsQL™ 3.0 DM) was used to evaluate the D-HRQOL. Data on diabetic ketoacidosis (DKA) at T1D onset, insulin therapy, and glycosylate hemoglobin (HbA1c) were also collected. Results: Group A (n=40), compared to Group B (n=85), had higher frequency of DKA at T1D onset (p<0.001) and a lower use of sensor augmented insulin pump (p=0.015). HbA1c values were higher in Group A than in Group B (p<0.001). Patients' "Diabetes symptoms" (p=0.004), "Treatment barriers" (p=0.001), and "Worry" (p=0.009) scales scores were lower in Group A than in Group B. Mothers of Group A had lower scores in "Diabetes symptoms" (p=0.030), "Treatment barriers" (p<0.001), "Treatment adherence" (p=0.018), "Communication" (p=0.009) scales, and total score (p=0.011) compared to the Group B ones. High PedsQL™ 3.0 DM was significantly associated with being Italian, being pre-pubertal, and having lower HbA1c mean levels. Conclusions: Being a migrant confers disadvantages in terms of D-HRQOL and metabolic control in children and adolescents with T1D. Specific educational interventions should be considered in the clinical care of patients with migration background, to improve D-HRQOL and health status.


2020 - Italian COVID-19 epidemic: Effects on paediatric emergency attendance - A survey in the Emilia Romagna region [Articolo su rivista]
Cella, A.; Marchetti, F.; Iughetti, L.; Di Biase, A. R.; Graziani, G.; De Fanti, A.; Valletta, E.; Vaienti, F.; Vergine, G.; Viola, L.; Biasucci, G.
abstract

Objective To evaluate the effect of the COVID-19 epidemic on paediatric emergency department (ED) attendance in a region of Northern Italy. Methods A survey was proposed to six out of nine paediatric EDs in the Emilia Romagna region to evaluate attendance data, distribution by age and gender, triage code score, outcome of clinical course, number of hospitalisations and the distribution of patients by disease. Data were collected during March 2020 and compared with that of March 2019. Results A drop in paediatric ED attendance of more than 83.8% was observed, with a higher percentage of infants and severe triage scores. The proportion of patients hospitalised was significantly higher in 2020 than in 2019 (p value: <0.001). The effect size for the comparison of proportions of hospitalised patients was 0.379. Looking at the distribution of attendance by type of disease, a significantly different distribution was highlighted (p value: <0.00001, Cramer's V); there was a greater proportion of patients presenting to paediatric EDs with poisonings (effect size=0.07), psychiatric pathologies (effect size=0.110), head injuries (effect size=0.167) and fever (effect size=0.212). Conclusions Our survey suggests that in the first month of the COVID-19 epidemic in Italy, there has been an increase in delayed attendance and provision of care of potentially severe diseases in paediatric EDs. Hospital and community paediatricians should be aware of this phenomenon and adopt appropriate strategies to prevent this danger, as it may affect children more seriously than COVID-19 itself.


2020 - Lo stridore vien leggendo [Articolo su rivista]
Leo, Francesco; Fontijn, Simone; Bergamini, Barbara Maria; Iughetti, Lorenzo
abstract


2020 - Markers of Inflammation and Endothelial Dysfunction in Young Survivors from Acute Lymphoblastic Leukemia [Articolo su rivista]
Bruzzi, Patrizia; Bigi, Elena; Felici, Francesca; Lami, Francesca; Cano Garcinuno, Maria Del Carmen; Palazzi, Giovanni; Cellini, Monica; Predieri, Barbara; Iughetti, Lorenzo
abstract

Purpose: To assess subclinical markers of endothelial inflammation in young survivors from acute lymphoblastic leukemia (ALL) treated with chemotherapy without cranial irradiation. Methods: Anthropometric parameters [height (H), body mass index (BMI), waist circumference (WC), hip circumference (HC), WC/H, and WC/HC ratio], blood pressure, lipid profile, serum markers of inflammation and endothelial dysfunction [Interleukin 6 (IL-6), vascular cell adhesion molecule, intercellular adhesion molecule, tumor necrosis factor-alfa (TNF-α), Endogenous secretory Receptor for Advanced Glycation Endproducts (Es-RAGE)], and carotid intima-media thickness (c-IMT) were assessed in a group of young ALL survivors and in matched controls. Local Ethics Committee approved the study (code 56/13) on June 24, 2013. Results: 28 ALL survivors (71% male, 18% prepubertal, aged 15.98 ± 4.41 years, mean follow-up 8.57 ± 3.14 years) exhibited lower levels of Es-RAGE than controls (0.18 ± 0.07 vs. 0.27 ± 0.08 ng/mL, p < 0.001). Among survivors, Es-RAGE values significantly correlated with BMI-SD off-therapy (R2 -0.42), WC/H ratio (R2 -0.41), WC/HC ratio (R2 -0.38), and low-density-lipoprotein cholesterol (LDL-C; R2 -0.43). Most of the ALL survivors (78%) presented c-IMT above the 95th centile if compared with gender and age standard. Mean c-IMT value correlated with blood pressure (R2 0.56) and with LDL-C levels (R2 0.56). Metabolic syndrome (MetS) was fully detected only in one ALL survivor. Nevertheless, 18% ALL survivors presented more than one MetS diagnostic criteria: 14% insulin resistance, 25% dyslipidemia, and 17.8% hypertension. Conclusions: We demonstrated an initial functional vascular alteration in young ALL survivors even when treated with standard risk protocols. Our data already support the activation at endothelial level of glycosylation and oxidation processes that are persistent long after the end of the treatment.


2020 - Mowat-Wilson syndrome: growth charts [Articolo su rivista]
Ivanovski, Ivan; Djuric, Olivera; Broccoli, Serena; Caraffi, Stefano Giuseppe; Accorsi, Patrizia; Adam, Margaret P; Avela, Kristina; Badura-Stronka, Magdalena; Bayat, Allan; Clayton-Smith, Jill; Cocco, Isabella; Cordelli, Duccio Maria; Cuturilo, Goran; Di Pisa, Veronica; Dupont Garcia, Juliette; Gastaldi, Roberto; Giordano, Lucio; Guala, Andrea; Hoei-Hansen, Christina; Inaba, Mie; Iodice, Alessandro; Nielsen, Jens Erik Klint; Kuburovic, Vladimir; Lazalde-Medina, Brissia; Malbora, Baris; Mizuno, Seiji; Moldovan, Oana; Møller, Rikke S; Muschke, Petra; Otelli, Valeria; Pantaleoni, Chiara; Piscopo, Carmelo; Poch-Olive, Maria Luisa; Prpic, Igor; Marín Reina, Purificación; Raviglione, Federico; Ricci, Emilia; Scarano, Emanuela; Simonte, Graziella; Smigiel, Robert; Tanteles, George; Tarani, Luigi; Trimouille, Aurelien; Valera, Elvis Terci; Schrier Vergano, Samantha; Writzl, Karin; Callewaert, Bert; Savasta, Salvatore; Street, Maria Elisabeth; Iughetti, Lorenzo; Bernasconi, Sergio; Giorgi Rossi, Paolo; Garavelli, Livia
abstract

Mowat-Wilson syndrome (MWS; OMIM #235730) is a genetic condition caused by heterozygous mutations or deletions of the ZEB2 gene. It is characterized by moderate-severe intellectual disability, epilepsy, Hirschsprung disease and multiple organ malformations of which congenital heart defects and urogenital anomalies are the most frequent ones. To date, a clear description of the physical development of MWS patients does not exist. The aim of this study is to provide up-to-date growth charts specific for infants and children with MWS. Charts for males and females aged from 0 to 16 years were generated using a total of 2865 measurements from 99 MWS patients of different ancestries. All data were collected through extensive collaborations with the Italian MWS association (AIMW) and the MWS Foundation. The GAMLSS package for the R statistical computing software was used to model the growth charts. Height, weight, body mass index (BMI) and head circumference were compared to those from standard international growth charts for healthy children.


2020 - Overwhelming sepsis in a neonate affected by Zellweger syndrome due to a compound heterozygosis in PEX 6 gene: a case report [Articolo su rivista]
Lucaccioni, L.; Righi, B.; Cingolani, G. M.; Lugli, L.; Della Casa, E.; Torcetta, F.; Iughetti, L.; Berardi, A.
abstract

Background: Peroxisome biogenesis disorders (PBDs) are a group of metabolic diseases caused by dysfunction of peroxisomes. Different forms of PBDs are described; the most severe one is the Zellweger syndrome (ZS). We report on an unusual presentation of Zellweger syndrome manifesting in a newborn with severe and fulminant sepsis, causing death during the neonatal period. Case presentation: A term male Caucasian neonate presented at birth with hypotonia and poor feeding associated with dysmorphic craniofacial features and skeletal abnormalities. Blood tests showed progressive leukopenia; ultrasounds revealed cerebral and renal abnormalities. He died on the fourth day of life because of an irreversible Gram-negative sepsis. Post-mortem tests on blood and urine samples showed biochemical alterations suggestive of ZS confirmed by genetic test. Conclusions: ZS is an early and severe forms of PBDs. Peroxisomes are known to be involved in lipid metabolism, but recent studies suggest their fundamental role in modulating immune response and inflammation. In case of clinical suspicion of ZS it is important to focus the attention on the prevention and management of infections that can rapidly progress to death.


2020 - Perimyocarditis as first sign of systemic onset juvenile idiopathic arthritis treated successfully with anakinra: A case-based review [Articolo su rivista]
Ciancia, S.; Cappella, M.; De Fanti, A.; Iughetti, L.
abstract

Background: The involvement of myocardium and pericardium at the same time is very uncommon as first manifestation of juvenile idiopathic arthritis with systemic onset (soJIA). Case: A fourteen years-old boy, referred with symptoms of acute gastroenteritis, developed a perimyocarditis as first manifestation of Still’s Disease, after only one day from the admission. The rheumatologic disease was not responding to glucocorticoid treatment. The use of anakinra was the key point of the therapy and after its administration the patient started to recover fastly. Conclusions: This case report describes cardiac involvement as first sign of soJIA and the successful use of anakinra inducing remission of soJIA not-responding to steroid therapy. (www.actabiomedica.it).


2020 - Risk factors for group B streptococcus early-onset disease: an Italian, area-based, case-control study [Articolo su rivista]
Berardi, Alberto; Spada, Caterina; Creti, Roberta; Ambretti, Simone; Chiarabini, Rossana; Barozzi, Agostino; Pagano, Rossella; Sarti, Mario; Pedna, Maria Federica; Fornaciari, Sara; Azzalli, Milena; Dodi, Icilio; Bacchi Reggiani, Maria Letizia; Lanzoni, Angela; Vaccina, Eleonora; Iughetti, Lorenzo; Lucaccioni, Laura
abstract

Purpose: Intrapartum antibiotic prophylaxis (IAP) prevents group B streptococcus (GBS) early-onset disease (EOD). No European study evaluates the relative impact of risk factors (RFs) for EOD after a screening-based strategy and widespread IAP use We aimed to evaluate the risks of EOD in an Italian region where a screening-based strategy for preventing EOD was implemented. Materials and methods: Cases of EOD born at or above 35 weeks' gestation were reviewed and matched with controls. Results: There were 109 cases of EOD among 532,154 live births. Most cases had negative GBS prenatal screening (56/91, 61.5%) and were unexposed to IAP (86/109, 78.9%). At multivariate analysis, GBS bacteriuria (OR = 6.99), positive prenatal screening (OR = 13.7) and maternal intrapartum fever (OR = 188.3) were associated with an increased risk of EOD, whereas intrapartum beta-lactam antibiotics were associated with a decreased risk of EOD (≥4 h: OR = 0.008; <4 h: OR = 0.04). Neonates born to nonfebrile, GBS positive pregnant women, receiving beta-lactam antibiotics had very low probability of EOD, particularly if IAP was adequate. Conclusions: GBS positive prenatal screening, GBS bacteriuria and intrapartum fever are associated with EOD. Intrapartum beta-lactam antibiotics reduce the probability of EOD in neonates born to nonfebrile mothers.


2020 - The "perfect" storm: Current evidence on pediatric inflammatory multisystem disease during SARS-CoV-2 pandemic [Articolo su rivista]
Lami, Francesca; Scalabrini, Ilaria; Lucaccioni, Laura; Iughetti, Lorenzo
abstract

Current data suggest that during the global pandemic of COVID 19 children are less affected than adults and most of them are asymptomatic or with mild symptoms. However, recently, cases of pediatric patients who have developed severe inflammatory syndrome temporally related to SARS-CoV-2 have been reported both in USA and Europe. These reports, although sharing features with other pediatric syndromes such as Kawasaki disease (KD), Kawasaki disease shock syndrome (KDSS), macrophage activated syndrome (MAS) and shock toxic syndrome (TSS), seem to outline a novel entity syndrome, characterized by cytokine storm with elevated inflammatory markers and typical clinical finding. Clinical characteristics are greater median age than KD, higher frequency of cardiac involvement and gastrointestinal symptoms, lower frequency of coronary anomalies. We report a summary of the current evidence about clinical features, pathogenesis, therapy strategies and outcome of this novel syndrome.


2020 - Tubercolosi primaria cavitaria in un lattante [Articolo su rivista]
Spaggiari, Valentina; Bonvicini, Federico; Filareto, Ilaria; Marastoni, Elisabetta; Amarri, Sergio; Iughetti, Lorenzo
abstract


2020 - UNA CEFALEA INSIDIOSA [Abstract in Rivista]
Ficara, Monica; Cenciarelli, Valentina; Bergonzini, Patrizia; Iughetti, Lorenzo
abstract


2019 - Anthropometric characteristics of newborns with Prader–Willi syndrome [Articolo su rivista]
Salvatoni, A.; Moretti, A.; Grugni, G.; Agosti, M.; Azzolini, S.; Bonaita, V.; Cianci, P.; Corica, D.; Crino, A.; Delvecchio, M.; Ferraris, S.; Greggio, N. A.; Iughetti, L.; Licenziati, M. R.; Madeo, S. F.; Nosetti, L.; Pajno, R.; Rutigliano, I.; Sacco, M.; Salvatore, S.; Scarano, E.; Trifiro, G.; Wasniewska, M.
abstract

This is a retrospective multicenter nationwide Italian study collecting neonatal anthropometric data of Caucasian subjects with Prader–Willi syndrome (PWS) born from 1988 to 2018. The aim of the study is to provide percentile charts for weight and length of singletons with PWS born between 36 and 42 gestational weeks. We collected the birth weight and birth length of 252 male and 244 female singleton live born infants with both parents of Italian origin and PWS genetically confirmed. Percentile smoothed curves of birth weight and length for gestational age were built through Cole's lambda, mu, sigma method. The data were compared to normal Italian standards. Newborns with PWS showed a lower mean birth weight, by 1/2 kg, and a shorter mean birth length, by 1 cm, than healthy neonates. Females with a 15q11-13 deletion were shorter than those with maternal uniparental maternal disomy of chromosome 15 (p <.0001). The present growth curves may be useful as further traits in supporting a suspicion of PWS in a newborn. Because impaired prenatal growth increases risk of health problems later in life, having neonatal anthropometric standards could be helpful to evaluate possible correlations between the presence or absence of small gestational age and some clinical and metabolic aspects of PWS.


2019 - Astenia degli arti inferiori e deficit della deambulazione: l’anamnesi e l’esame obiettivo prima di tutto. Due immagini a confronto [Articolo su rivista]
Zavattero, Chiara; Ciancia, Silvia; Caramaschi, Elisa; Iughetti, Lorenzo
abstract


2019 - Blu, le mille bolle blu [Articolo su rivista]
Filareto, Ilaria; Leone, Federica; Felici, Francesca; Iughetti, Lorenzo; Amarri, Sergio; Cappella, Michela; Defanti, Alessandro
abstract


2019 - Clinical characterization of neonatal and pediatric enteroviral infections: an Italian single center study [Articolo su rivista]
Berardi, Alberto; Sandoni, Marcello; Toffoli, Carlotta; Boncompagni, Alessandra; Gennari, William; Bergamini, Maria Barbara; Lucaccioni, Laura; Iughetti, Lorenzo
abstract

Enteroviruses (EVs) are an important cause of illness, especially in neonates and young infants. Clinical and laboratory findings at different ages, brain imaging, and outcomes have been inadequately investigated.


2019 - Dolore addominale in un’adolescente: e se fosse un problema di ormoni? [Articolo su rivista]
Ciancia, Silvia; Predieri, Barbara; Iughetti, Lorenzo
abstract


2019 - DOLORE LOMBOSACRALE IN ETÀ PEDIATRICA: BUON SANGUE NON MENTE, A CASE REPORT [Abstract in Atti di Convegno]
Bonvicini, F.; Pancaldi, A.; Russo, G.; Bigi, E.; Lami, F.; Palazzi, G.; Mariotti, I.; Cano Garcinuno, M. C.; Cellini, M.; Iughetti, L.
abstract


2019 - Endocrine and metabolic complications in children and adolescents with Sickle Cell Disease: An Italian cohort study [Articolo su rivista]
Mandese, V.; Bigi, E.; Bruzzi, P.; Palazzi, Giovanni; Predieri, B.; Lucaccioni, L.; Cellini, M.; Iughetti, L.
abstract

Background: Children with Sickle Cell Disease (SCD) show endocrine complications and metabolic alterations. The physiopathology of these conditions is not completely understood: iron overload due to chronic transfusions, ischemic damage, and inflammatory state related to vaso-occlusive crises may be involved. Aims of this study were to evaluate the growth pattern, endocrine complications, and metabolic alterations and to detect the relationship between these conditions and the SCD severity in affected children and adolescents. Methods: Fifty-two children and adolescents with SCD [38 homozygous sickle hemoglobin (HbSS) and 14 heterozygous sickle hemoglobin (HbSC); age range 3-18 years] were recruited. Anthropometric [height, body mass index (BMI), arm span, sitting height, target height (TH), and pubertal status] and laboratory [blood cell counts, hemolysis indices, metabolic and nutritional status indices and hormonal blood levels] data were evaluated. The SCD severity was defined according to hematological and clinical parameters. Results: Height-SDS adjusted for TH and BMI-SDS were significantly higher in HbSC children than in HbSS ones. Forty-eight out of 52 patients (92%) had at least one metabolic and/or endocrine alteration: insufficiency/deficiency of vitamin D (84.7%), insulin resistance (11.5%), growth hormone deficiency (3.8%), subclinical hypothyroidism (3.8%), and hypogonadism (1.9%). Levels of vitamin D were significantly and negatively correlated with clinical indicators of the SCD severity. Subjects with HbSS genotype show significant lower levels of both insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein 3 than children with HbSC. In the study population IGF-1 values were significantly and positively correlated with Hb and negatively with lactate dehydrogenase. Conclusions: Metabolic alterations and endocrine complications are very common in children and adolescents with SCD. A regular follow-up is necessary to identify subjects at risk for complications to precociously start an appropriate treatment and to improve the quality of life of SCD patients.


2019 - Endothelial and heart dysfunction in children and adolescents with type 1 diabetes [Abstract in Rivista]
Predieri, Barbara; Lami, Francesca; Cenciarelli, Valentina; Ciancia, Silvia; Righi, Beatrice; Madeo, Simona F.; Bruzzi, Patrizia; Prampolini, Beatrice; Iughetti, Lorenzo
abstract

Background/Objectives: Type 1 diabetes (T1D) is an important risk factor for cardiovascular disease (CVD). Even if CVD become mainly manifest in adulthood, the process of atherosclerosis starts in childhood. Ultrasound is a reliable and noninvasive method for detecting early structural and functional atherosclerotic changes in arterial wall and heart. Aim of this study was to determine early ultrasound signs of atherosclerosis and of left ventricular (LV) systolic and diastolic dysfunction in children and adolescents with T1D. Methods: Ninety-four subjects with T1D [12.3±3.53 yrs.; males 59.6%; T1D duration 5.14±3.53 years) were enrolled into the study. Carotid intima-media thickness (cIMT), systolic and diastolic function indices were determined according to standardized scanning protocol and were performed by the same investigator blinded to subjects’ anthropometric (Ht, Wt, BMI, pubertal status, WC, SBP/DBP) and laboratory data (HbA1c, TC, LDL-C, HDL-C, TG). Results: cIMT, LV systolic and diastolic function indices were all in the normal range defined for healthy population. Pubertal subjects, respect to pre-pubertal ones, had significantly higher values of cIMT (0.60±0.09 vs. 0.49±0.08 mm; p<0.001), interventricular septal end-diastole (IVSd) (7.27±1.27 vs. 6.61±1.00 mm; p=0.027), deceleration time (DT) (138.3±31.7 vs. 112.6±20.9 ms; p<0.001), and isovolumetric relaxation time (IVRT) (60.8±14.1 vs. 53.1±9.58 ms; p=0.006). Patients with DKA at T1D onset had significantly higher values of IVSd respect to subjects without DKA 7.40±1.22 vs. 6.80±1.17 mm; p=0.018). Moreover, DBP (Chi-Square=6.13; p=0.047), LV internal dimension at end-iastole (LVIDd) (Chi-Square=7.25; p=0.027), A wave peak (Chi-Square=6.11; p=0.047), and IVRT (Chi-Square=7.29; p=0.026) were significantly different according to mean HbA1c value in the last year. cIMT was higher in subjects with a worse glycemic control (HbA1c ≥9%) (Chi-Square=5.07; p=0.079) and cIMT was significantly correlated with age (R=0.51, p<0.001), WC (R=0.39, p<0.001), SBP (R=0.41, p<0.001), mean HbA1c values of the first 5 years of T1D (R=0.24, p=0.021), TG (R=0.23, p=0.029), and TG/HDL-C ratio (R=0.22, p=0.034). The multivariate regression model was statistically significant for cIMT (R2=0.44, p<0.001) and identify T1D duration (β= -0.23; p=0.024) and LDL-C levels (β=0.20, p=0.031) as predictor factors. Conclusions: cIMT were within normal range but, despite the good glycemic and lipid control, mean values were significantly higher respect to published ones in healthy and T1D children and adolescents. Moreover, LV diastolic function was slightly abnormal. Ultrasound is useful for early detection of subjects with a greater cardiovascular risk who can benefit from targeted therapeutic interventions.


2019 - Evaluation of endothelial function in childhood standard risk acute lymphoblastic leukemia survivors: role of subclinical markers and identification of preventable factors [Abstract in Rivista]
Patrizia, Bruzzi; Bigi, Elena; Francesca, Felici; Righi, Beatrice; Carmen, Cano; Monica, Cellini; Predieri, Barbara; Iughetti, Lorenzo
abstract

Background: Adult survivors from childhood malignancy are prone to accelerated atherogenesis and cardiovascular (CV) complications. In this population reliable tools are needed to detect preclinical onset of CV disease. Aim: To assess subclinical markers of inflammation and endothelial dysfunction in young survivors from acute lymphoblastic leukemia (ALL) treated with chemotherapy without cranial irradiation (AIEOP 2000 and 2009 standard risk protocols). Methods: Anthropometric parameters [height (H), body mass index (BMI), waist circumference (WC), hip circumference (HC), WC/H and WC/HC ratio], blood pressure, glucose and lipid profile, serum CV markers [Interleukin 6 (IL-6), Vascular Cell Adhesion Molecule (VCAM), Intercellular Adhesion Molecule (ICAM), Tumor Necrosis Factor-alfa (TNF-α), endogenous secretory Receptor for Advanced Glycation Endproducts (Es-RAGE)] and ultrasound parameters of endothelial function (carotid intima–media thickness, c-IMT) were assessed in 28 ALL survivors (71% male, 18% prepubertal, aged 15.98±4.41 years) at least two years after the end of chemotherapy (mean follow-up 8.57±3.14 years) and in 22 sex- and age-matched controls (64% male, aged 16.59±5.60 years). Results: ALL survivors exhibited low levels of Es-RAGE than controls (0.18±0.07 vs. 0.27±0.08 ng/ml, p<0.001). No other differences in serum CV markers were detected between survivors and controls. Among survivors, Es-RAGE values significantly correlated with BMI-SDS off-therapy (R2-0.42), WC/H ratio (R2-0.41), WC/HC ratio (R2-0.38) and with low-density-lipoprotein cholesterol (LDL-c; R2-0.43). IL-6 and TNF-α levels directly correlated with WC/H ratio (R20.41), WC/HC ratio (R20.51), triglycerides values (R20.40) and with diastolic blood pressure (DBP; R20.50), respectively. Moreover, in ALL survivors, mean c-IMT was within the normal range for age (0.55±0.14 mm, range 0.4-0.85) and correlated with systolic blood pressure (SBP; R20.56), DBP (R20.66) and LDL-c levels (R20.56). According to Weiss’ definition, metabolic syndrome (MetS) was fully detected only in one ALL survivor. Nevertheless, 18% ALL survivors presented more than one MetS diagnostic criteria: 14% showed insulin-resistance, 25% dyslipidemia and 17.8% hypertension. Conclusions: We demonstrated that in ALL survivors, as in general population, all the investigated CV markers correlate with modifiable clinical and biochemical parameters. Therefore, a healthy lifestyle should be encouraged soon after chemotherapy. The detection of low levels of Es-RAGE in ALL survivors could be due to their consumption in a chronic endothelial inflammatory condition that seems to be only partially reversible after chemotherapy.


2019 - Extra Uterine Growth Restriction (EUGR) in very low birth weight infants: Growth recovery and neurodevelopment by the corrected age of 2 years old [Abstract in Rivista]
Lucaccioni, Laura; Arrigoni, Marta; Elisa Della Casa, ; Natascia, Bertoncelli; Predieri, Barbara; Berardi, Alberto; Pugliese, Marisa; Ferrari, Fabrizio; Iughetti, Lorenzo
abstract

Background: Extra Uterine Growth Restriction (EUGR) represents a serious comorbidity in infants born very low birth weight (VLBW). In fact, failure in postnatal growth and malnutrition at vulnerable ages can interfere with growth recovery and neurodevelopment at older ages. Hypothesis: Aim of the study was to assess whether and how the postnatal early growth patterns of VLBW may affect later growth, spontaneous motility at three months of corrected age (CA) and neurodevelopment at 2 years CA. Study Design: Retrospective single-centre study of 547 infants (255M) born VLBW between 2005 and 2015. Each participant underwent: a) anthropometric assessments of weight (W), length (L) and head circumference (HC) at birth, at discharge from the NICU and at 2 years CA; b) Evaluation of Fidgety movements (F) at three months CA; c) Neurodevelopmental assessment at 2 years CA through the Griffith Mental Development Scales. Results: From the overall population, growth percentiles at discharge were significantly lower than at birth (L p<0.01; W p<0.01; HC p< 0.01). Longitudinal data showed a significant growth restriction between birth (AGA for W:73%; AGA for L:73.2%) and discharge (AGA for W:36%; AGA for L:31.2%). Gestational age, duration of hospitalisation, bronchopulmonary dysplasia and intra ventricular haemorrhage were found to be predictive factors for EUGR at discharge. At 2 years CA, SGA at discharge but not at birth, showed significantly lower stature compared to the AGA ones (p:0.04). Significant correlation was found between F and L (p:0.04; r:0.12) and HC (p<0.02; r:0.2) at discharge, but not at birth. Moreover, a significant difference was found between F and locomotor outcome at two years CA (p<0.01). W and L at discharge, but not at birth, were significantly related to worse locomotor outcome at two years of CA (respectively, p:0.03, r:0.14; p:0.01, r:0.18). In particular, who was found SGA at discharge, both for W and/or L, had the worse motor outcome compared to the AGA ones (respectively, p:0.04 and p:0.01). Conclusions: VLBW growth measurements at discharge, but not at birth, are related to poorer growth and neurodevelopment at later ages, especially in children who become SGA. Lower scores in locomotor assessment at two years CA have been observed in infants with anomalies of F, suggesting how spontaneous motility could predict later neurodevelopmental outcomes. Our findings highlight the necessity of a close clinical follow-up of growth patterns during preterm hospitalization aiming to decrease the incidence of EUGR.


2019 - Familial neurohypophyseal diabetes insipidus in 13 kindreds and 2 novel mutations in the vasopressin gene [Articolo su rivista]
Patti, G.; Scianguetta, S.; Roberti, D.; Di Mascio, A.; Balsamo, A.; Brugnara, M.; Cappa, M.; Casale, M.; Cavarzere, P.; Cipriani, S.; Corbetta, S.; Gaudino, R.; Iughetti, L.; Martini, L.; Napoli, F.; Peri, A.; Salerno, M. C.; Salerno, R.; Passeri, E.; Maghnie, M.; Perrotta, S.; Di Iorgi, N.
abstract

Background: Autosomal dominant neurohypophyseal diabetes insipidus (adNDI) is caused by arginine vasopressin (AVP) deficiency resulting from mutations in the AVP-NPII gene encoding the AVP preprohormone. Aim: To describe the clinical and molecular features of Italian unrelated families with central diabetes insipidus. Patients and methods: We analyzed AVP-NPII gene in 13 families in whom diabetes insipidus appeared to be segregating. Results: Twenty-two patients were found to carry a pathogenic AVP-NPII gene mutation. Two novel c.173 G>C (p.Cys58Ser) and c.215 C>A (p.Ala72Glu) missense mutations and additional eight different mutations previously described were identified; nine were missense and one non-sense mutation. Most mutations (eight out of ten) occurred in the region encoding for the NPII moiety; two mutations were detected in exon 1. No mutations were found in exon 3. Median age of onset was 32.5 months with a variability within the same mutation (3 to 360 months). No clear genotype–phenotype correlation has been observed, except for the c.55 G>A (p.Ala19Thr) mutation, which led to a later onset of disease (median age 120 months). Brain magnetic resonance imaging (MRI) revealed the absence of posterior pituitary hyperintensity in 8 out of 15 subjects, hypointense signal in 4 and normal signal in 2. Follow-up MRI showed the disappearance of the posterior pituitary hyperintensity after 6 years in one case. Conclusion: adNDI is a progressive disease with a variable age of onset. Molecular diagnosis and counseling should be provided to avoid unnecessary investigations and to ensure an early and adequate treatment.


2019 - Febbre e zoppia: sacroileite settica da Salmonella [Articolo su rivista]
Scalabrini, Ilaria; Maisano, Flavia; Marrozzini, Lucia; Cingolani, Greta; Crestani, Sara; Lami, Francesca; Iughetti, Lorenzo
abstract


2019 - Febbre in lattante, non solo sepsi [Articolo su rivista]
Crestani, Sara; Cingolani, Greta; Maisano, Flavia; Scalabrini, Ilaria; Marrozzini, Lucia; Lami, Francesca; Iughetti, Lorenzo
abstract


2019 - FP808EARLY IDENTIFICATION OF SICKLE CELL NEPHROPATHY IN A COHORT OF CHILDREN WITH SICKLE CELL DISEASE [Abstract in Rivista]
Fontana, Francesco; Giovanella, Silvia; Ligabue, Giulia; Alfano, Gaetano; Lodi, Mariachiara; Bigi, Elena; Palazzi, Giovanni; Varani, Manuela; Iughetti, Lorenzo; Cappelli, Gianni
abstract


2019 - Ghrelin plasma levels after 1 year of ketogenic diet in children with refractory epilepsy [Articolo su rivista]
Marchiò, Maddalena; Roli, Laura; Lucchi, Chiara; Costa, ANNA MARIA; Borghi, Matteo; Iughetti, Lorenzo; Trenti, Tommaso; Guerra, Azzurra; Biagini, Giuseppe
abstract

The ketogenic diet (KD) is a high-fat, low carbohydrate nutritional treatment adopted in several countries for refractory epilepsy. However, the use of KD is limited by adverse events including growth retardation. In a previous investigation, we demonstrated that ghrelin is reduced in children maintained on KD for 3 months. As ghrelin regulates growth hormone (GH) secretion, it can be hypothesized that growth retardation depends on the reduced ghrelin availability. To assess this hypothesis, in this study we evaluate ghrelin and growth during 1 year of KD. We examined a small cohort of 6 children (2 males and 4 females, age range 3–10.4 years) affected by refractory epilepsy, who received the KD as add-on treatment. All patients were on drug polytherapy. Endpoints of the study were: (i) ghrelin plasma levels at 0, 15, 30, 90, and 365 days from KD onset, (ii) growth, and (iii) seizure control by ketogenesis. Ghrelin levels were −53 and −47% of basal levels, respectively, at 90 and 365 days (P < 0.05 for both). Mean height index z scores were reduced, but not significantly, by comparing basal values with those at the end of observation. Instead, body mass index z scores slightly increased. Ketosis induced by the KD was within 2–5 mmol/L and satisfactorily reduced the seizure frequency (>50%) in all patients. We show that ghrelin plasma levels are consistently reduced in children with refractory epilepsy and maintained on the KD. This change was associated with low growth indexes in the majority of patients.


2019 - Health-Related Quality of Life and Diabetes Control in Immigrant and Italian Children and Adolescents with Type 1 Diabetes and in their Parents [Abstract in Rivista]
Predieri, Barbara; Boncompagni, Alessandra; Patrizia, Bruzzi; Cenciarelli, Valentina; Madeo, Simona F.; Pugliese, Marisa; Toffoli, Carlotta; Federica, Bocchi; Iughetti, Lorenzo
abstract

Background/Objectives: Type 1 diabetes (T1D) is a chronic metabolic disease that requires daily and complex management for both patients and their caregivers, impairing the quality of life. Aim of this cross-sectional observational study was to determine whether metabolic control and health-related quality of life (HRQOL) of T1D subjects and their parents could be influenced by immigration status. Methods: We enrolled 125 children and adolescents with T1D (12.4±3.55 years; males 53.6%; T1D duration 5.61±3.50 years) and their parents (102 mothers and 37 fathers). According to patients’ maternal origin, the study population was categorized into Group A (immigrant) and Group B (Italian). The Italian translation of the PedsQL™ 3.0 Diabetes Module was used to evaluate the HRQOL. Information on presence of diabetic ketoacidosis (DKA) at T1D onset, insulin therapy (MDI/SAP), and glycosylate hemoglobin (HbA1c), were collected at the same time of the questionnaire. Results: Group A, respect to Group B, had significantly higher frequency of DKA at T1D onset (55.0 vs. 22.3%; Chi-square=13.1; p<0.001) and a significant lower use of SAP (5.0 vs. 22.3%; Chi-Square=5.86; p=0.015). HbA1c values were significantly higher in Group A respect to Group B (72.7±17.6 vs. 62.6±12.9 mmol/mol; p<0.001). Patients’ HRQOL scores were significantly lower in Group A than in Group B in the following scales: “Diabetes selfsymptoms” (57.9±14.6 vs. 66.9±12.8; p=0.004), “Treatment barriers” (68.1±23.6 vs. 82.9±13.0; p=0.001), and “Worry” (52.9±26.9 vs. 66.9±23.7; p=0.009). Mothers’ HRQOL scores were significantly lower in Group A than in Group B in the following scales: “Diabetes self-symptoms” (56.7±18.1 vs. 65.8±15.7; p=0.030), “Treatment barriers” (55.9±19.8 vs. 71.3±19.7; p<0.001), “Treatment adherence” (71.2±18.1 vs. 80.6±11.2; p=0.018), “Communication” (58.9±31.4 vs. 75.9±23.3; p=0.009) scales, and total score (57.2±17.1 vs. 68.8±12.6; p=0.011). No differences were found in fathers’ data. The multivariate regression model for child HRQOL scales identified the following significant predictive factors: MDI insulin therapy ('=0.438; p=0.008), Italian ethnicity ('=0.018; p=0.004), HbA1c ('=-0.228; p=0.029) for “Treatment barriers” scale; Italian ethnicity ('=0.584; p=0.046) for “Worry” scale. Conclusions: Our results strongly suggest that immigrant status confers significant disadvantages in terms of T1D treatment, glycemic control, and HRQOL in children and adolescents with T1D. Moreover, parents’ HRQOL data suggest that daily T1D management is usually supervised by mothers rather than fathers. Specific challenges and educational interventions should be considered in clinical care of T1D patients with distinct migration background.


2019 - Hypospadias: clinical approach, surgical technique and outcome. Twenty years’ experience of a single centre [Abstract in Rivista]
Lucaccioni, Laura; Francesca, Poluzzi; Viviana, Durante; Predieri, Barbara; Iughetti, Lorenzo; Ceccarelli, PIER LUCA
abstract

Background: Hypospadias is one of the most common congenital abnormalities in male. Nowadays, hypospadias surgical repair has become highly demanding and deeply investigated with more than 300 corrective procedures. Its success is assessed by the “reoperation rate” that occurs short after the surgery within a brief follow-up (6-12 months). However, short-term outcomes may not reflect the long-term ones, as hypospadias repair may influence adolescence and adult life. This study aims to identify the cosmetic, functional and psychosexual outcomes on a long-term follow-up and to suggest an innovative approach to the hypospadiac patient’s care, as well as providing a review of a singol center experience. Methods: Medical records of 398 patients treated by the same surgeon for hypospadias between August 2001 and December 2017 were reviewed. Families were reached by phone and invited to attend a free-charge follow-up examination. A life-related interview and 3 validated questionnaires (the Penile Perception Score-PPS, the Hypospadias Objective Score Evaluation-HOSE, the International Index of Erectile Function-5-IIEF5) were used, according to the age, to compare the parents’, patients’ and surgeon’s opinion on long-term outcomes. Results: 187 patients were included in the study (response rate 47%). 46 patients (24.6%) presented at least one complication after the repair with a mean elapsed time of 17.6 months (SD 18,96). Longitudinal differences in surgical corrective procedures (p<0.01), clinical approach (p<0.01) and hospitalisation after surgery (p<0.01) were found. Cosmetic data from the PPS were similar among patients and parents, with no significant differences according to patients’ age nor to the type of hypospadias: 83% of the patients and 87% of the parents were satisfied with the cosmetic result. A significant difference in functional outcome relating to the type of hypospadias was reflected by the HOSE among patients (p<0.001), parents (p:0.02) and surgeon (p<0.01). Patients’ HOSE total score was consistently lower compared to the surgeon one (p<0.01). The HOSE satisfaction rate on functional outcome was 89% for patients and 92% for parents. No data were available from the IIEF5 questionnaire. Conclusion: Long-term hypospadias outcomes still represent a debated issue for scientific community and a standardized approach to evaluate the consequences of surgery through time is needed. We propose an innovative algorithm in attempt to fill the gap of the present literature.


2019 - IDENTIFICAZIONE PRECOCE DEL DANNO RENALE IN PAZIENTI PEDIATRICI ED ADOLESCENTI AFFETTI DA DREPANOCITOSI.RUOLO DELLA CISTATINA-C [Abstract in Rivista]
Bigi, E.; Cattini, U.; Lodi, M.; Pancaldi, A.; Predieri, B.; Varani, M.; Fontana, F.; Cantatore, S.; Palazzi1, G.; Iughetti, L.
abstract

La MAU nei pazienti con SCD compare prima della riduzione del GFR. La correlazione della Cys-C sia con MAU sia con eGFR dimostra il potenziale ruolo di questo marker nel monitoraggio del danno renale. La scintigrafia renale con DTPA potrebbe aiutare ad identificare le equazioni con migliore sensibilità e specificità nella stima del GFR.


2019 - Inability of Asian risk scoring systems to predict intravenous immunoglobulin resistance and coronary lesions in Kawasaki disease in an Italian cohort [Articolo su rivista]
Fabi, Marianna; Andreozzi, Laura; Corinaldesi, Elena; Bodnar, Tetyana; Lami, Francesca; Cicero, Cristina; Tchana, Bertrand; Landini, Chiara; Sprocati, Monica; Bigucci, Barbara; Balsamo, Claudia; Sogno Valin, Paola; Di Fazzio, Giorgia; Iughetti, Lorenzo; Valletta, Enrico; Marchetti, Federico; Donti, Andrea; Lanari, Marcello
abstract

Since resistance to intravenous immunoglobulin (IVIG) is associated with coronary lesions (CALs) in Kawasaki disease (KD), it is crucial to identify patients at risk to protect them from coronary involvement. The available risk scores to predict IVIG resistance were developed in Asian populations in whom their effectiveness has been proven, but data on non-Asian children are limited. The aim of this study is to evaluate the ability of the Kobayashi, Egami, and Formosa risk scores to predict IVIG resistance and CALs in Italian patients with KD. A multicenter retrospective analysis involving children with KD diagnosed between 2000 and 2015 was carried out: 257 patients were enrolled (57.9% boys, 89.9% Caucasian); 43 patients were IVIG resistant (16.7%). The scores have low sensitivity and specificity in predicting IVIG resistance: respectively, KS 64% and 62.5%, ES 41.4% and 77.4%, and FS 70.8% and 44.9%. The predictive value of the 3 scores for predicting CALs was also poor. Conclusion: Kobayashi, Egami, and Formosa Scores are ineffective in predicting IVIG resistance and coronary involvement in a predominantly Caucasian cohort. A specific score system for mostly Caucasian children with KD is needed enable the early identification of those at risk for CALs who could benefit from intensified treatment.What is Known:• There are several risk scores developed in the Asian population to early identify patients with KD at risk for immunoglobulin-resistance and thus for coronary lesions.• Data are scarce on their effectiveness in non-Asian children.What is New:• We present a comprehensive analysis of the ability of 3 Asian risk scores in a cohort of mostly Caucasian children to predict immunoglobulin resistance and coronary involvement.• Low sensitivity and specificity of the Asian scores for immunoglobulin-resistance and coronary lesions suggest the need for criteria specific for different ethnicities.


2019 - IperCKemia: un riscontro occasionale, una diagnosi per la vita [Articolo su rivista]
Passini, Erica; Crestani, Sara; Canovi, Alessio; Caramaschi, Elisa; Iughetti, Lorenzo
abstract


2019 - Isolated hypoaldosteronism as first sign of X-linked adrenal hypoplasia congenita caused by a novel mutation in NR0B1/DAX-1 gene: a case report [Articolo su rivista]
Iughetti, Lorenzo; Lucaccioni, Laura; Bruzzi, Patrizia; Ciancia, Silvia; Bigi, Elena; Madeo, Simona Filomena; Predieri, Barbara; Roucher-Boulez, Florence
abstract

X-linked Adrenal Hypoplasia Congenita (AHC) is a rare cause of primary adrenal insufficiency due to mutations in the NR0B1 gene, causing a loss of function of the nuclear receptor protein DAX-1. Adrenal insufficiency usually appears in the first 2 months of life, but can sometimes emerge during childhood. Hypogonadotropic Hypogonadism is often associated later in life and patients may develop azoospermia. We describe an unusual onset of AHC started with isolated hypoaldosteronism as first and only sign of the disease.


2019 - Linfangioma cistico neonatale: descrizione di un caso clinico [Articolo su rivista]
Bonvicini, Federico; Baraldi, Alessandro; Lugli, Licia; Torcetta, Francesco; Rossi, Katia; Berardi, Alberto; Iughetti, Lorenzo
abstract

Il linfangioma cistico è una rara malformazione linfatica benigna a prevalente insorgenza nelle regioni cervico-facciale e ascellare. Le forme viscerali sono rare, mentre cute e mucose sono mag- giormente colpite. La diagnosi prenatale ecografica è possibile, tuttavia la maggior parte insorge a fine gestazione. In epoca pos - tnatale, in caso di masse atipiche, può essere necessario, oltre alla stadiazione in RM, procedere all’analisi citologica per escludere lesioni di natura maligna. L’ escissione chirurgica non è esente da complicanze procedurali e sovente risulta incompleta portando a recidive locali. In casi selezionati è possibile considerare laser- terapia, scleroterapia e la terapia farmacologica [1]. Le principali complicanze sono infezioni, emorragie, idrotorace e/o chiloto- race.


2019 - Long-term effects on growth, development, and metabolism of ALL treatment in childhood [Articolo su rivista]
Bruzzi, Patrizia; Bigi, Elena; Predieri, Barbara; Bonvicini, Federico; Cenciarelli, Valentina; Felici, Francesca; Iughetti, Lorenzo
abstract

One aim of the long-term care in survivors from acute lymphoblastic leukemia (ALL) during childhood is to avoid or limit complications caused by aggressive therapeutic strategies. Areas covered: ALL survivors are a heterogeneous group according to therapeutic protocols. In the last decades, cranial radiotherapy (cRT) has been largely replaced by intrathecal chemotherapy (CT) with a reduction of endocrine sequelae. Published studies are generally difficult to be interpreted because patients were treated according to different risk-adapted protocols and results are conflicting. We perform this review on endocrine long-term effects in childhood ALL survivors focusing on studies published in the last decades. Articles were selected using the following terms (Mesh terms): 'acute lymphoblastic leukemia' AND 'survivors' AND 'childhood' AND 'growth/puberty/fertility/obesity/metabolic syndrome/bone'. Expert commentary: Most childhood ALL survivors treated with CT alone attain normal height and have adequate pubertal development. Despite recent protocols improvements, ALL survivors still develop long-term metabolic complications (overweight, obesity, and cardiovascular disease) especially the female gender and patients with an increased body mass index (BMI) at diagnosis. The aim of this review is to describe the state of the art on these topics. We should be able to anticipate, prevent, and treat endocrine long-term morbidities through a well-established follow-up strategy.


2019 - MicroRNAs change and target key regulatory genes involved in longitudinal growth in patients with idiopathic isolated growth hormone deficiency (IGHD) on growth hormone (GH) treatment [Abstract in Rivista]
Cirillo, Francesca; Catellani, Cecilia; Lazzeroni, Pietro; Sartori, Chiara; Ravegnini, Gloria; Bonvicini, Federico; Predieri, Barbara; Amarri, Sergio; Iughetti, Lorenzo; Angelini, Sabrina; Elisabeth Street, Maria
abstract

The growth response in patients undergoing GH treatment is variable depending both on the patient’s basal conditions and on personal innate sensitivity to therapy. MicroRNAs (miRNAs) are epigenetic regulators of gene expression, and are recognised as important regulators of biological and metabolic processes. It is unknown at present whether miRNAs could be early biomarkers of response to GH treatment in a perspective of individualised medicine, and whether they could disclose new information on the effects and regulation of GH. We aimed at identifying all miRNAs varying on GH treatment using a global profiling approach, and at evaluating the principal pathways and biological processes, within growth, impacted by these miRNAs. Ten prepubertal normal weight patients with IGHD were enrolled (5Males,5Females; CA:8,12±0,73yr). Global miRNA profiles (TaqMan Advanced Human CardA) were evaluated at -3, 0 and at +3 months on treatment. MiRNA expression levels at -3 and 0 months were compared and the miRNAs showing a p-value≤0.05 were excluded allowing to identify those miRNAs changing only in response to treatment (+3 months) by either a factor Log22-DDCt>+1.5 or Log22-DDCt<-1.5 (up- or downregulated, respectively). Single miRNA target genes were evaluated and DIANA-miRPathv3.0 software was used for KEGG pathway and Gene Ontology analyses. Overall 30 miRNAs were regulated by GH, 27 were upregulated, and 3 down-regulated. A subset of 8 showed the most stringent criteria. Interestingly, 13 miRNAs were specifically regulated in females only and other 13 in males only, suggesting gender-specific effects. In the entire population, the miRNAs identified, targeted genes involved in the following pathways: ExtraCellularMatrix-receptor (COL1A1, COL2A1, integrins, laminins, SOX9, NF1 genes,etc.), Thyroid hormone (THReceptor, ATP1B2, MAP2K2, PIK3R2, RAF1, NOTCH2, AKT, CASP9, STAT1, FOXO1, MAPK1, etc.), Steroid biosynthesis, mTOR signaling (BRAF, AKT, PIK3CD, IGF1, PTEN, etc.), MAPK signaling (BRAF, SOS2, FGFR3, RAF1, FGF4, EGFR, TGFB1, FGF11, AKT, FLNB, FGF9, NF1, TGFB2, FGFs, FGFRs, TGFB3, etc.), Prolactin signaling (PRLR, STAT3, SOS2, SHC1, RAF1, AKT2, JAK2, SOCS1, FOXO3, STAT1, SOCS7, etc.), PI3K-Akt signaling (FGFR3, FGFR4, COL4A5, IGF1R, EGFR, COL5A1, COL1A1, INSR, IGF1, VEGFB, FGFR1, FGF7, SOS2, RAF1, FGF8, etc.), Phosphatidylinositol signaling (PIK3R3, PTEN, etc.), and N-Glycan biosynthesis pathways. Mutations of 15 of these genes are well known to cause genetic short stature in humans. Furthermore, analyses of the biological processes identified the following as being regulated by the miRNAs identified: fibroblast growth factor receptor signaling, glycosaminoglycan metabolism, phosphatidylinositol-mediated signaling (FGFR3, IGF1R, PTPN11, IGF1, FGF8, FGFR1, etc.), insulin receptor signaling, transforming growth factor beta receptor signaling, androgen receptor signaling and the JAK-STAT cascade involved in GH signaling as expected. In conclusion, GH regulates miRNAs that in turn regulate genes, pathways and biological processes involved with growth. Novel gender specific effects of GH were found. MiRNAs could be explored as biomarkers of response to treatment. Further, some novel genes implicated in the regulation of growth could be identified using this approach.


2019 - Motor and Postural Patterns Concomitant with General Movements Are Associated with Cerebral Palsy at Term and Fidgety Age in Preterm Infants [Articolo su rivista]
Ferrari, Fabrizio; Plessi, Carlotta; Lucaccioni, Laura; Bertoncelli, Natascia; Bedetti, Luca; Ori, Luca; Berardi, Alberto; Della Casa, Elisa; Iughetti, Lorenzo; D'Amico, Roberto
abstract

General movements (GMs) in combination with neurological examination and magnetic resonance imaging at term age can accurately determine the risk of cerebral palsy. The present study aimed to assess whether 11 motor and postural patterns concomitant with GMs were associated with cerebral palsy. Video recordings performed after birth in 79 preterm infants were reviewed retrospectively. Thirty-seven infants developed cerebral palsy at 2 years corrected age and the remaining 42 showed typical development. GMs were assessed from preterm to fidgety age and GM trajectories were defined. The 11 motor and postural patterns were evaluated at each age and longitudinally, alone and in combination with GM trajectories. A logistic regression model was used to assess the association between GMs, concomitant motor and postural patterns, and cerebral palsy. We confirmed that high-risk GM trajectories were associated with cerebral palsy (odds ratio = 44.40, 95% confidence interval = 11.74-167.85). An association between concomitant motor and postural patterns and cerebral palsy was found for some of the patterns at term age and for all of them at fidgety age. Therefore, at term age, concomitant motor and postural patterns can support GMs for the early diagnosis of cerebral palsy.


2019 - Newborn screening in Nigeria: Associating the screening of congenital hypothyroidism and sickle cell disease can be a winning choice? [Articolo su rivista]
Yarhere, Iroro Enameguolo; Jaja, Tamunopriye; Briggs, Datonye; Iughetti, Lorenzo
abstract

ntroduction: Nigeria like many African countries has tried to start the newborn screening for congenital hypothyroidism and many failed. Since sickle cell disease is more common in Nigeria, the hypothesis is that incorporating it into a screening programme for congenital hypothyroidism will improve the uptake of the programme by parents and government.


2019 - Non semplice magrezza… [Articolo su rivista]
Miceli, Andrea; Madeo, Simona Filomena; Madeo, Bruno; Iughetti, Lorenzo
abstract


2019 - Obesity in pediatric age: The analysis of genomic rearrangements [Abstract in Rivista]
Filomena Madeo, Simona; Ciancia, Silvia; Leo, Francesco; Bruzzi, Patrizia; Predieri, Barbara; Stanghellini, Ilaria; Calabrese, Olga; Iughetti, Lorenzo
abstract

Childhood obesity became a global plague: 9% of Italian children (17% of USA children) is obese and 21% is overweight. Nowadays only a small number of obese children undergoes genetic analysis, usually when obesity is associated with dysmorphic features. Our purpose was to identify genomic rearrangement causing obesity: we analyzed the DNA of 52 children by array-CGH (platform CytoScan-HD, Affymetrix). Patients included in our study were 29 males (55,8%) and 23 females (44,2%) obese, they presented dysmorphic features and/or mental retardation, hyperphagia and the improvement of the nutritional approach was not having any benefit reducing their weight. The average BMI was 28.42 kg/m 2 (SDS 2.64). 24 patients (46,15%) resulted positive on array-CGH analysis (33,4% females, 66,6% males); among these patients 41,2% presented dysmorphic features and 50% were affected by mental retardation. In 8 patients with a genetic rearrangement this was related to obesity and in 1 patient the link was suspected but not proved. Genetic rearrangements identified that can be causative of obesity are 4 deletions and 4 duplications. Del16p11.2 (813kb e 232kb) are described in association with obesity in childhood; dupXp22.31(1,6Mb) (genes HDHD1, STS, VCX, PNPLA4) causes over-expression of PNPLA4, that has been related to obesity. Genetic rearrangements of single genes are two dup18q(393 kb) and one del7q21.3(55kb), involving respectively genes ONECUT2 and BAIAP2L1, coding for molecules part of insulin pattern signaling. Dup3q24q25.1(180kb) and del20q13.13(109kb) code for CP and STAU1: among obese patients have been described mutations of these two genes but their pathogenetic role has not be clarified yet. Del6q21(33kb) involves gene LAMA4: this rearrangement has an undefined meaning; in animal models LAMA4 seems to have a function in development of fatty tissue but in humans this function is not known yet. 46,15 % of patients of our cohort presented array-CGH positive for genomic rearrangements and this data justifies the execution of genetic analysis in obese children presenting dysmorphic features and/or mental retardation. 33,3% of our patients resulted positive on array-CGH analysis in absence of dysmorphic features and/or mental retardation, so genomic analysis could have an important role either in obese patients without syndromic features. We can affirm that in obese children array-CGH analysis could help in identification of causative genetic mutations, with consequent advantage in therapeutic management and follow-up of these patients.


2019 - Occhio alla macrorchidia! [Articolo su rivista]
Pietrella, Elisa; Marrozzini, Lucia; Bruzzi, Patrizia; Bigi, Elena; Repetto, Paolo; Ceccarelli, PIER LUCA; Cellini, Monica; Iughetti, Lorenzo
abstract

L’ incremento del volume testicolare in epoca prepuberale è un segno da indagare innanzi tutto nel sospetto di pubertà precoce, senza escludere a priori altre cause.


2019 - Oral communications presented by graduates to the 30th National Congress of the Pediatric Cultural Association [Articolo su rivista]
Ciancia, S.; Di Biase, A. R.; Iughetti, L.; Guarnieri, M.; Lucca, F.; Cecchin, V.; Dal Ben, S.; Perlini, S.; Banzato, C.; Biban, P.; Piacentini, G.; Martini, L.; Pecoraro, L.; Tadiotto, E.; Clemente, M.; Degani, D.; Piacentini, G.; Baldo, F.; Barbi, E.; Murri, V.; Degani, D.; Neri, M.; Cesaro, S.; Boner, A. L.
abstract


2019 - Perché fare il trial con Piridossina nelle convulsioni neonatali refrattarie: un caso di epilessia PNPO responsiva alla Piridossina [Articolo su rivista]
Bariola, Maria Carolina; Russo, Giovanna; Iughetti, Lorenzo; Berardi, Alberto; Ferrari, Fabrizio; Lugli, Licia
abstract

L’epilessia piridossino dipendente (PDE) e l’epilessia piridossal/fosfato dipendente (PNPO) sono difficilmente distinguibili da un punto di vista clinico: si caratterizzano per spasmi mioclonici (talora a esordio prenatale), associati a irritabilità, insonnia e startles.


2019 - Pitfalls in the diagnosis of meningitis in neonates and young infants: the role of lumbar puncture [Articolo su rivista]
Bedetti, Luca; Marrozzini, Lucia; Baraldi, Alessandro; Spezia, Elisabetta; Iughetti, Lorenzo; Lucaccioni, Laura; Berardi, Alberto
abstract

Meningitis occurs frequently in neonates and can lead to a number of acute, severe complications and long-term disabilities. An early diagnosis of neonatal meningitis is essential to reduce mortality and to improve outcomes. Initial clinical signs of meningitis are often subtle and frequently overlap with those of sepsis, and current haematologic tests do not distinguish sepsis from meningitis. Thus, lumbar puncture remains the gold standard for the diagnosis of meningitis in infants, and this procedure is recommended in clinical guidelines. Nevertheless, in clinical practice, lumbar puncture is frequently deferred or omitted due to concerns regarding hypothetical adverse events or limited experience of the performer. Future studies should assess whether a combination of clinical findings and select haematological tests at disease onset can identify those neonates with the highest risk of meningitis who should undergo lumbar puncture. Furthermore, clinicians should be convinced that the actual benefits of an early diagnosis of meningitis far outweigh the hypothetical risks associated with lumbar puncture.


2019 - Quando l’ anatomia è alla base [Articolo su rivista]
Russo, Giovanna; Bonvicini, Federico; Cinelli, Giulia; Marastoni, Elisabetta; Felici, Francesca; Fornaciari, Sara; Iughetti, Lorenzo; Amarri, Sergio
abstract


2019 - Quando l’ittero persiste, attenti ai geni [Articolo su rivista]
Righi, Beatrice; Bianchedi, Ilaria; Rita Di Biase, Anna; Iughetti, Lorenzo
abstract


2019 - Severe metabolic alkalosis due to diuretic treatment in a patient with distal renal tubular acidosis: a rare association. [Articolo su rivista]
Lucaccioni, Laura; Coccolini, Elena; Dozza, Alessandra; Cantatore, Sante Lucio; Berardi, Alberto; Predieri, Barbara; Iughetti, Lorenzo
abstract

Introduction: Distal renal tubular acidosis is a rare genetic disease, characterised by deficit in renal tubular transport. Clinical features are metabolic acidosis with hypercloraemia and hypokalemia, and inability in urine acidification. Hypercalciuria may also be present, often treated with the use of a diuretic therapy with thiazides. Case Presentation: We present a severe disease onset in a neonate with consanguineous parents, both autosomal-recessive for an ATP6VOA4 gene mutation, and a nevertheless severe episode of metabolic alkalosis, occurred in the same patient after few months, during the diuretic therapy. Conclusion: Biochemical results lead us to hypothesize a susceptibility to the treatment that need further investigations.


2019 - Tenere i farmaci lontano dalla portata dei bambini [Articolo su rivista]
Cinelli, Giulia; Zini, Annalisa; Ficara, Monica; Russo, Giovanna; Iughetti, Lorenzo; Amarri, Sergio
abstract


2019 - The oral communications presented by post graduate students in pediatrics at the Conference: From Tabiano to Parma [Relazione in Atti di Convegno]
Bariola, M. C.; Russo, G.; Iughetti, L.; Berardi, A.; Ferrari, F.; Lugli, L.; Giulia, L. A.; Euro, C.; Monica, S.; Rita, G. M.; Giuseppe, M.
abstract


2019 - Thyroid function in patients with Prader-Willi syndrome: an Italian multicenter study of 339 patients [Articolo su rivista]
Iughetti, Lorenzo; Vivi, Giulia; Balsamo, Antonio; Corrias, Andrea; Crinò, Antonino; Delvecchio, Maurizio; Gargantini, Luigi; Greggio, Nella Augusta; Grugni, Graziano; Hladnik, Uros; Pilotta, Alba; Ragusa, Letizia; Salvatoni, Alessandro; Wasniewska, Malgorzata; Weber, Giovanna; Predieri, Barbara
abstract

Background Prader-Willi syndrome (PWS) is a genetic disorder due to loss of expression of paternally transcribed genes of the imprinted region of chromosome 15q11-13. PWS is characterized by peculiar signs and symptoms and many endocrine abnormalities have been described (growth hormone deficiency, hypogonadotropic hypogonadism). The abnormalities of thyroid function are discussed in literature and published data are discordant. The aim of our study was to report the thyroid function in patients with PWS to identify the prevalence of thyroid dysfunction. Methods Thyroid function tests were carried out in 339 patients with PWS, aged from 0.2 to 50 years. A database was created to collect personal data, anthropometric data, thyroid function data and possible replacement therapy with L-thyroxine. Subjects were classified according to thyroid function as: euthyroidism (EuT), congenital hypothyroidism (C-HT), hypothyroidism (HT - high thyroid-stimulating hormone [TSH] and low free thyroxine [fT4]), central hypothyroidism (CE-H - low/normal TSH and low fT4), subclinical hypothyroidism (SH - high TSH and normal fT4), and hyperthyroidism (HyperT - low TSH and high fT4). Results Two hundred and forty-three out of 339 PWS patients were younger than 18 years (71.7%). The prevalence of thyroid dysfunction was 13.6%. Specifically, C-HT was found in four children (1.18%), HT in six patients (1.77%), CE-H in 23 patients (6.78%), SH in 13 patients (3.83%), and HyperT in none. All other subjects were in EuT (86.4%). Conclusions Hypothyroidism is a frequent feature in subjects with PWS. Thyroid function should be regularly investigated in all PWS patients both at the diagnosis and annually during follow-up.


2019 - Un bambino vittima di abuso, una donna spettatrice silenziosa e il gravoso compito del pediatra [Articolo su rivista]
Ciancia, Silvia; Rita Di Biase, Anna; Iughetti, Lorenzo
abstract

n.a.


2019 - Un distress grave… per un soffio! [Articolo su rivista]
Piqué, Margherita; Ceccoli, Martina; Fornaciari, Sara; Lami, Francesca; Amarri, Sergio; Iughetti, Lorenzo
abstract


2019 - Un neonato a termine ipotonico [Articolo su rivista]
Bariola, Maria Carolina; Vaccina, Eleonora; Lugli, Licia; Iughetti, Lorenzo; Ferrari, Fabrizio
abstract

Il caso descritto rappresenta un esempio di sindrome di Prader-Willi diagnosticata in epoca neonatale.


2019 - Un neonato a termine ipotonico: pensa anche alla sindrome di Prader-Willi [Articolo su rivista]
Bariola, Maria Carolina; Vaccina, E.; Lugli, L.; Berardi, A.; Lucaccioni, L.; Iughetti, L.; F. Ferrari.,
abstract

The paper describes the case of a term newborn infant, born by elective caesarean section with no prenatal and perinatal risk factors. He presented with an unexpected cardiorespiratory depression at birth, severe hypotonia, feeding problems and peculiar dysmorphism: micrognathia with chubby cheeks, small hands and right cryptorchidism. In the suspect of Prader-Willi syndrome, DNA methylation test confirmed the diagnostic hypothesis. The simultaneous presence of neonatal hypotonia, poor suck and peculiar dysmorphism should suggest Prader-Willi syndrome and thus the performance of the DNA methylation test to confirm the diagnosis for a timely and adequate therapeutic work-up.


2019 - Un versamento ostinato [Articolo su rivista]
Russo, Giovanna; Ficara, Monica; Cinelli, Giulia; Marastoni, Elisabetta; Fornaciari, Sara; Iughetti, Lorenzo; Amarri, Sergio
abstract

In presenza di polmonite con versamento pleurico, dopo aver escluso gli agenti infettivi più probabili per età, in caso di manca- ta risposta alle terapie empiriche e in presenza di fattori di rischio epidemiologici in anamnesi, andrà ricercata l’ eziologia tuberco- lare del quadro polmonare. Quest’ ultima andrà esclusa anche nei casi di versamento pleurico isolato, non altrimenti spiegato, in pazienti provenienti da paesi ad alta endemia.


2019 - Un viaggio complicato [Articolo su rivista]
Cinelli, Giulia; Elisabetta, Marastoni; Zini, Annalisa; Ficara, Monica; Russo, Giovanna; Iughetti, Lorenzo; Amarri, Sergio
abstract


2019 - Una lesione che dà nell’occhio [Articolo su rivista]
Toffoli, Carlotta; Cenciarelli, Valentina; Caramaschi, Elisa; Guerra, Azzurra; Iughetti, Lorenzo
abstract


2019 - Una polmonite… a buco! Storia di una lobectomia [Articolo su rivista]
Piqué, Margherita; Fornaciari, Sara; Amarri, Sergio; Iughetti, Lorenzo
abstract


2019 - Una ptosi palpebrale recidivante [Articolo su rivista]
Cenciarelli, Valentina; Toffoli, Carlotta; Caramaschi, Elisa; Guerra, Azzurra; Iughetti, Lorenzo
abstract


2019 - Uniparental disomy and pretreatment IGF-1 may predict elevated IGF-1 levels in Prader-Willi patients on GH treatment [Articolo su rivista]
Palmieri, V. V.; Lonero, A.; Bocchini, S.; Cassano, G.; Convertino, A.; Corica, D.; Crino, A.; Fattorusso, V.; Ferraris, S.; Fintini, D.; Franzese, A.; Grugni, G.; Iughetti, L.; Lia, R.; Macchi, F.; Madeo, S. F.; Matarazzo, P.; Nosetti, L.; Osimani, S.; Pajno, R.; Patti, G.; Pellegrin, M. C.; Perri, A.; Ragusa, L.; Rutigliano, I.; Sacco, M.; Salvatoni, A.; Scarano, E.; Stagi, S.; Tornese, G.; Trifiro, G.; Wasniewska, M.; Fischetto, R.; Giordano, P.; Licenziati, M. R.; Delvecchio, M.
abstract

Pediatric patients with Prader-Willi syndrome (PWS) can be treated with recombinant human GH (rhGH). These patients are highly sensitive to rhGH and the standard doses suggested by the international guidelines often result in IGF-1 above the normal range. We aimed to evaluate 1 the proper rhGH dose to optimize auxological outcomes and to avoid potential overtreatment, and 2 which patients are more sensitive to rhGH. In this multicenter real-life study, we recruited 215 patients with PWS older than 1 year, on rhGH at least for 6 months, from Italian Centers for PWS care. We collected auxological parameters, rhGH dose, IGF-1 at recruitment and (when available) at start of treatment. The rhGH dose was 4.3 (0.7/8.4) mg/m2/week. At recruitment, IGF-1 was normal in 72.1% and elevated in 27.9% of the patients. In the group of 115 patients with IGF-1 available at start of rhGH, normal pretreatment IGF-1 and uniparental disomy were associated with elevated IGF-1 during the therapy. No difference in height and growth velocity was found between patients treated with the highest and the lowest range dose. The rhGH dose prescribed in Italy seems lower than the recommended one. Normal pretreatment IGF-1 and uniparental disomy are risk factors for elevated IGF-1. The latter seems to be associated with higher sensitivity to GH. In case of these risk factors, we recommend a more accurate titration of the dose to avoid overtreatment and its potential side effects.


2019 - Unusual meningitis caused by non-typhoid Salmonella in an italian infant: a case report. [Articolo su rivista]
Ficara, Monica; Cenciarelli, Valentina; Montanari, Lisa; Righi, Beatrice; Fontjin, Simone; Cingolani, Greta Miriam; Predieri, Barbara; Berardi, Alberto; Lucaccioni, Laura; Iughetti, Lorenzo
abstract

Background: Non-typhoid Salmonella (NTS) is an important cause of bacterial meningitis in newborn and infants in developing countries, but rarely in industrialized ones. We describe an unusual presentation of bacterial meningitis in an infant, focusing on his diagnostic and therapeutic management. Case report: An Italian two-month old male presented high fever and diarrhea with blood, associated with irritability. Inflammatory markers were high, cerebrospinal fluid analysis was compatible with bacterial meningitides but microbiological investigations were negative. Salmonella enteritidis was isolated from blood. Cerebral ultrasound and MRI showed periencephalic collection of purulent material. Specific antibiotic therapy with cefotaxime was initiated with improvement of clinical conditions and blood tests. Brain MRI follow up improved progressively. Conclusions: Most of pediatric patients with NTS infection develop self-limited gastroenteritis, but in 3-8% of the cases complications such as bacteremia and meningitis may occur, especially in weak patients. Cerebral imaging can be useful to identify neurological findings. Although there is no standardized treatment for this condition, specific antibiotic therapy for at least four weeks is recommended. Neuroimaging follow up is required due to high risk of relapse.


2019 - Weekend-Based Parent-Group Intervention to Reduce Stress in Parents of Children and Adolescents with Type 1 Diabetes: A Pilot Study [Articolo su rivista]
Ferrito, Lucia; Predieri, Barbara; Pjetraj, Dorina; Alessandrelli, Maria Cristina; Pagnini, Manuela; Iannilli, Antonio; Marino, Monica; Tombolini, Stefano; Pintaudi, Basilio; Lucisano, Giuseppe; Zani, Fabiana; Iughetti, Lorenzo; Nicolucci, Antonio; Cherubini, Valentino
abstract

Diagnosis of type 1 diabetes (T1D) in a child is often associated with anger, denial, fear, and depression from the parents. The aim of the study was to improve parents' adaptation to the diagnosis of diabetes of their child. Sixty-two parents (29 mothers, 33 fathers) of 36 children with type 1 diabetes (mean age=11.3-3.3 years; diabetes duration>1 year; HbA1c=57 +/- 11 mmol/mol) participated in a three-day educational working group pilot intervention study. Intervention was based on the reexamination of the traumatic event of diagnosis of T1D through spatial and time-line anchorage, retracing of the future, emotional awareness, and interactive discussion. Relaxing technique, diaphragmatic breathing, and guided visualization were used by 2 psychologists and 1 pediatric endocrinologist. The study was approved by EC and participants filled a consent form. At baseline and after intervention, parents filled in a questionnaire including Diabetes-Related Distress (DRD), Parent Health Locus of Control Scale (PHLOC), Parent Stress Index Short Form (PSI-SF), Hypoglycemia Fear Survey-Parents (HFS-P) and Hypoglycemia Fear Survey-Parents of Young Children (HFS-P-YC), and Health Survey Short Form-36 (SF-36). Three months after the intervention, both parents reported a reduction in the "difficult child" subscale of the PSI-SF (p<0.05) and increased scores of social functioning of the SF-36 (p<0.05). DRD score was significantly reduced in mothers (p=0.03), while the "parental distress" subscale of the PSI-SF was significantly improved in fathers (p=0.03). This weekend-based parent group intervention seems to reduce stress and improve social functioning of parents of children and adolescents with type 1 diabetes.


2018 - Adrenal Hypoplasia Seemingly First as a Primary Hypoaldosteronism [Abstract in Rivista]
Iughetti, Lorenzo; Lucaccioni, Laura; Bruzzi, Patrizia; Ciancia, Silvia; Predieri, Barbara; Roucher-Boulez, Florence
abstract

Background: X-linked Congenital Adrenal Hypoplasia (AHC) is a rare cause of primary adrenal insufficiency due to mutations in NR0B1 gene, causing a loss of function of the nuclear receptor protein DAX-1. Adrenal insufficiency usually presents in the first two months of life, but sometimes can appear later in childhood. Hypogonadotropic Hypogonadism is often associated later in life and all patients develop azoospermia. We describe an unusual onset of AHC started with isolated hypoaldosteronism as first and only sign of disease. Case presentation: A 18-days-old newborn presented with failure to thrive and feeding difficulties. Blood tests showed severe hyponatremia, hyperkalemia and hypochloremia. Renin was found over the measurable range and aldosterone was low whereas cortisol level was normal with a slightly increased ACTH. In the suspicion of Primary Hypoaldosteronism, correction of plasmatic electrolytes and replacement therapy with Fludrocortisone were promptly started. The subsequent evidence of low plasmatic and urinary cortisol and increased ACTH required the start of Hydrocortisone replacement therapy and it defined a clinical picture of adrenal insufficiency. Genetic analysis demonstrated a novel mutation in DAX-1 gene leading to the diagnosis of AHC. Conclusions: NR0B1/DAX-1 mutations should be considered in male infants presenting with isolated hypoaldosteronism as first sign of adrenal insufficiency.


2018 - Brain-derived neurotrophic factor and epilepsy: a systematic review [Articolo su rivista]
Iughetti, L; Lucaccioni, L; Fugetto, F; Predieri, B; Berardi, A; Ferrari, F.
abstract

Several in vitro, ex vivo and in vivo studies imply brain-derived neurotrophic factor (BDNF) in the pathophysiology of epilepsy. Aim of our work is to report the most important findings regarding BDNF and its potential role in epilepsy. We targeted those publications addressing both in vitro and in vivo evidences of relationship between BDNF and epilepsy. Basic researches, randomized trials, cohort studies, and reviews were contemplated to give a breadth of clinical data. Medline, CENTRAL, and Science Direct were searched till August 2017 using keywords agreed by the authors. Together with a defined role in developmental and mature brain, BDNF has excitatory effects in neuronal cultures and animal brain slices. Furthermore, both BDNF and its conjugated receptor (i.e. Tropomyosin receptor kinase B or TrkB) are increased in animal models and humans with epilepsy, particularly in the temporal and hippocampal areas. Acute injection of BDNF in brain of mice induces seizures, which are almost or totally abolished blocking its transcription and pathway. Chronic infusion of BDNF is conversely associated with a decreased neuronal excitability, probably via several mechanism including an increase in central levels of neuropeptide Y (NPY), altered conductance of chloride, and downregulation of TrkB. While genetic studies are inconclusive, serum BDNF is more frequently higher in patients with epilepsy and appears to be correlated to severity of disease. Current evidences suggest that inhibiting BDNF-TrkB signaling and reinforcing the NPY system could represent a potential therapeutic strategy for epilepsy, especially for temporal lobe epilepsy.


2018 - Can HbA1c combined with fasting plasma glucose help to assess priority for GCK-MODY vs HNF1A-MODY genetic testing? [Articolo su rivista]
Delvecchio, Maurizio; Salzano, Giuseppina; Bonura, Clara; Cauvin, Vittoria; Cherubini, Valentino; D’Annunzio, Giuseppe; Franzese, Adriana; Giglio, Sabrina; Grasso, Valeria; Graziani, Vanna; Iafusco, Dario; Iughetti, Lorenzo; Lera, Riccardo; Maffeis, Claudio; Maltoni, Giulio; Mantovani, Vilma; Menzaghi, Claudia; Patera, Patrizia I.; Rabbone, Ivana; Reindstadler, Petra; Scelfo, Sabrina; Tinto, Nadia; Toni, Sonia; Tumini, Stefano; Lombardo, Fortunato; Nicolucci, Antonio; Barbetti, Fabrizio
abstract

n.a.


2018 - Cardiopulmonary anomalies in incontinentia pigmenti patients [Articolo su rivista]
Onnis, Giuliana; Diociaiuti, Andrea; Zangari, Paola; D'Argenio, Patrizia; Cancrini, Caterina; Iughetti, Lorenzo; El Hachem, May
abstract

Background: Incontinentia pigmenti (IP) is a rare inherited genodermatosis that usually involves the skin, and also teeth, oral cavity, central nervous system, eyes, blood with eosinophilia, and rarely skeletal system, breast, heart, and lungs. Skin lesions usually appear early, at birth or within the first 2 weeks of life, with four different phases tending to follow Blaschko lines that may overlap. Case report: We report a rare case of a neonate with transient reversible pulmonary hypertension that presented at day 9 of life. She manifested increasing dyspnea and deterioration of respiratory dynamics with a serious pulmonary hypertension without a primary pulmonary disease. Hence, oxygen therapy at high flows and nitric oxide have been administered with an initial response, but, subsequently, because of the worsening of the respiratory activity, she underwent sildenafil and bosentan treatment with respiratory dynamics improvement and progressive decrease of the pulmonary pressures. Conclusion: In literature only a few cases of cardiopulmonary anomalies in IP have been described with different outcomes, and these rare complications are probably underestimated by physicians. We could suppose that microangiopathic damages may have a critical role in endothelial alterations, and these processes are probably shared by multiple organs involved in IP and rarely by lungs and heart.


2018 - Current Knowledge on Endocrine Disrupting Chemicals (EDCs) from Animal Biology to Humans, from Pregnancy to Adulthood: Highlights from a National Italian Meeting [Articolo su rivista]
Elisabeth Street, Maria; Angelini, Sabrina; Bernasconi, Sergio; Burgio, Ernesto; Cassio, Alessandra; Catellani, Cecilia; Cirillo, Francesca; Deodati, Annalisa; Fabbrizi, Enrica; Fanos, Vassilios; Gargano, Giancarlo; Grossi, Enzo; Iughetti, Lorenzo; Lazzeroni, Pietro; Mantovani, Alberto; Migliore, Lucia; Palanza, Paola; Panzica, Giancarlo; Maria Papini, Anna; Parmigiani, Stefano; Predieri, Barbara; Sartori, Chiara; Tridenti, Gabriele; Amarri, Sergio
abstract

Wildlife has often presented and suggested the effects of endocrine disrupting chemicals (EDCs). Animal studies have given us an important opportunity to understand the mechanisms of action of many chemicals on the endocrine system and on neurodevelopment and behaviour, and to evaluate the effects of doses, time and duration of exposure. Although results are sometimes conflicting because of confounding factors, epidemiological studies in humans suggest effects of EDCs on prenatal growth, thyroid function, glucose metabolism and obesity, puberty, fertility, and on carcinogenesis mainly through epigenetic mechanisms. This manuscript reviews the reports of a multidisciplinary national meeting on this topic.


2018 - Diagnosis, treatment and prevention of pediatric obesity: consensus position statement of the Italian Society for Pediatric Endocrinology and Diabetology and the Italian Society of Pediatrics [Articolo su rivista]
Valerio, Giuliana; Maffeis, Claudio; Saggese, Giuseppe; Ambruzzi, Maria Amalia; Balsamo, Antonio; Bellone, Simonetta; Bergamini, Marcello; Bernasconi, Sergio; Bona, Gianni; Calcaterra, Valeria; Canali, Teresa; Caroli, Margherita; Chiarelli, Francesco; Corciulo, Nicola; Crinò, Antonino; Di Bonito, Procolo; Di Pietrantonio, Violetta; Di Pietro, Mario; Di Sessa, Anna; Diamanti, Antonella; Doria, Mattia; Fintini, Danilo; Franceschi, Roberto; Franzese, Adriana; Giussani, Marco; Grugni, Graziano; Iafusco, Dario; Iughetti, Lorenzo; Lamborghini, Adima; Licenziati, Maria Rosaria; Limauro, Raffaele; Maltoni, Giulio; Manco, Melania; Reggiani, Leonardo Marchesini; Marcovecchio, Loredana; Marsciani, Alberto; Del Giudice, Emanuele Miraglia; Morandi, Anita; Morino, Giuseppe; Moro, Beatrice; Nobili, Valerio; Perrone, Laura; Picca, Marina; Pietrobelli, Angelo; Privitera, Francesco; Purromuto, Salvatore; Ragusa, Letizia; Ricotti, Roberta; Santamaria, Francesca; Sartori, Chiara; Stilli, Stefano; Street, Maria Elisabeth; Tanas, Rita; Trifiró, Giuliana; Umano, Giuseppina Rosaria; Vania, Andrea; Verduci, Elvira; Zito, Eugenio
abstract

The Italian Consensus Position Statement on Diagnosis, Treatment and Prevention of Obesity in Children and Adolescents integrates and updates the previous guidelines to deliver an evidence based approach to the disease. The following areas were reviewed: (1) obesity definition and causes of secondary obesity; (2) physical and psychosocial comorbidities; (3) treatment and care settings; (4) prevention.The main novelties deriving from the Italian experience lie in the definition, screening of the cardiometabolic and hepatic risk factors and the endorsement of a staged approach to treatment. The evidence based efficacy of behavioral intervention versus pharmacological or surgical treatments is reported. Lastly, the prevention by promoting healthful diet, physical activity, sleep pattern, and environment is strongly recommended since the intrauterine phase.


2018 - Endocrine and Metabolic Complications in Children and Adolescents with Sickle Cell Disease: An Italian Cohort Study [Abstract in Rivista]
Elena, Bigi; Bruzzi, Patrizia; Giovanni, Palazzi; Predieri, Barbara; Lucaccioni, Laura; Pancaldi, Alessia; Lodi, Mariachiara; Monica, Cellini; Iughetti, Lorenzo
abstract

Background: Children with Sickle Cell Disease (SCD) show endocrine complications and metabolic alterations. The physiopathology of these conditions is not completely understood: iron overload due to chronic transfusions, ischemic damage, and inflammatory state related to vaso-occlusive crises may be involved. Aims of this study were to evaluate the growth pattern and the endocrine and metabolic alterations in a cohort of children with SCD and to detect the relationship between these conditions and the SCD severity. Methods: Fifty-two children and adolescents with SCD [38 homozygous sickle hemoglobin (HbSS) and 14 heterozygous sickle hemoglobin (HbSC); age range 3-18 years] were recruited. Anthropometric [height, body mass index (BMI), arm span, sitting height, target height (TH), and pubertal status] and laboratory [blood cell counts, hemolysis indices, metabolic and nutritional status indices and hormonal blood levels] data were evaluated. The SCD severity was defined according to hematological and clinical parameters. Results: Height-SDS adjusted for TH and z-score-BMI were significantly higher in HbSC children than in HbSS ones. The 92% (48/52) of the population show at least one metabolic and/or endocrine alteration: insufficiency/deficiency of vitamin D (84.7%), insulin resistance (11.5%), growth hormone deficiency (3.8%), subclinical hypothyroidism (3.8%), and hypogonadism (1.9%). Levels of 25-hydroxy-vitamin D were negatively correlated with clinical indicators of the SCD severity. Subjects with HbSS genotype show significant lower levels of both insulin-like growth factor-I (IGF-1) and insulin-like growth factor binding protein 3 than children with HbSC. In the study group IGF-1 values were positively related with Hb and negatively related with lactate dehydrogenase. Conclusions: Metabolic and endocrine alterations are very common in children and adolescents with SCD. A regular follow-up is necessary to identify subjects at risk for complications, to precociously initiate an appropriate treatment, and to improve the quality of life of SCD patients.


2018 - Evaluation of the performance of Dutch Lipid Clinic Network score in an Italian FH population: The LIPIGEN study [Articolo su rivista]
Casula, Manuela; Olmastroni, Elena; Pirillo, Angela; Catapano, Alberico Luigi; Arca, Marcello; Averna, Maurizio; Bertolini, Stefano; Calandra, Sebastiano; Tarugi, Patrizia; Pellegatta, Fabio; Angelico, Francesco; Bartuli, Andrea; Biasucci, Giacomo; Biolo, Gianni; Bonanni, Luca; Bonomo, Katia; Borghi, Claudio; Bossi, Antonio Carlo; Branchi, Adriana; Carubbi, Francesca; Cipollone, Francesco; Citroni, Nadia; Federici, Massimo; Ferri, Claudio; Fiorenza, Anna Maria; Giaccari, Andrea; Giorgino, Francesco; Guardamagna, Ornella; Iannuzzi, Arcangelo; Iughetti, Lorenzo; Lupattelli, Graziana; Lupi, Alessandro; Mandraffino, Giuseppe; Marcucci, Rossella; Maroni, Lorenzo; Miccoli, Roberto; Mombelli, Giuliana; Muntoni, Sandro; Pecchioli, Valerio; Pederiva, Cristina; Pipolo, Antonio; Pisciotta, Livia; Pujia, Arturo; Purrello, Francesco; Repetti, Elena; Rubba, Paolo; Sabbà, Carlo; Sampietro, Tiziana; Sarzani, Riccardo; Tagliabue, Milena Paola; Trenti, Chiara; Vigna, Giovanni Battista; Werba, Josè Pablo; Zambon, Sabina; Zenti, Maria Grazia; Minicocci, Ilenia; Noto, Davide; Fortunato, Giuliana; Banderali, Giuseppe; Benso, Andrea; Bigolin, Paola; Bonora, Enzo; Bruzzi, Patrizia; Bucci, Marco; Buonuomo, Paola Sabrina; Capra, Maria Elena; Cardolini, Iris; Cefalù, Baldassarre; Cervelli, Nazzareno; Chiariello, Giuseppe; Cocci, Guido; Colombo, Emanuela; Cremonini, Anna Laura; D'addato, Sergio; D'erasmo, Laura; Dal Pino, Beatrice; De Sanctis, Luisa; De Vita, Emanuele; Del Ben, Maria; Di Costanzo, Alessia; Di Taranto, Maria Donata; Fasano, Tommaso; Gentile, Luigi; Gentile, Marco; Ghirardello, Omar; Grigore, Liliana; Lussu, Milena; Meregalli, Giancarla; Moffa, Simona; Montalcini, Tiziana; Morgia, Valeria; Nascimbeni, Fabio; Pasta, Andrea; Pavanello, Chiara; Saitta, Antonino; Scicali, Roberto; Siepi, Donatella; Spagnolli, Walter; Spina, Rossella; Sticchi, Elena; Suppressa, Patrizia; Vigo, Lorenzo; Vinci, Pierandrea; Manzato, Enzo; Tragni, Elena; Zampoleri, Veronica
abstract

Background and aims: Familial hypercholesterolemia (FH) is an inherited disorder characterized by high levels of blood cholesterol from birth and premature coronary heart disease. Thus, the identification of FH patients is crucial to prevent or delay the onset of cardiovascular events, and the availability of a tool helping with the diagnosis in the setting of general medicine is essential to improve FH patient identification. Methods: This study evaluated the performance of the Dutch Lipid Clinic Network (DLCN) score in FH patients enrolled in the LIPIGEN study, an Italian integrated network aimed at improving the identification of patients with genetic dyslipidaemias, including FH. Results: The DLCN score was applied on a sample of 1377 adults (mean age 42.9 ± 14.2 years) with genetic diagnosis of FH, resulting in 28.5% of the sample classified as probable FH and 37.9% as classified definite FH. Among these subjects, 43.4% had at least one missing data out of 8, and about 10.0% had 4 missing data or more. When analyzed based on the type of missing data, a higher percentage of subjects with at least 1 missing data in the clinical history or physical examination was classified as possible FH (DLCN score 3–5). We also found that using real or estimated pre-treatment LDL-C levels may significantly modify the DLCN score. Conclusions: Although the DLCN score is a useful tool for physicians in the diagnosis of FH, it may be limited by the complexity to retrieve all the essential information, suggesting a crucial role of the clinical judgement in the identification of FH subjects.


2018 - Gastrointestinal presentation of kawasaki disease: A red flag for severe disease? [Articolo su rivista]
Fabi, Marianna; Corinaldesi, Elena; Pierantoni, Luca; Mazzoni, Elisa; Landini, Chiara; Bigucci, Barbara; Ancora, Gina; Malaigia, Laura; Bodnar, Tetyana; Fazzio, Giorgia Di; Lami, Francesca; Valletta, Enrico; Cicero, Cristina; Biasucci, Giacomo; Iughetti, Lorenzo; Marchetti, Federico; Valin, Paola Sogno; Amarri, Sergio; Brusa, Sandra; Sprocati, Monica; Maggiore, Giuseppe; Dormi, Ada; Lanzoni, Paolo; Donti, Andrea; Lanari, Marcello
abstract

Background Kawasaki disease (KD) is a febrile systemic vasculitis of unknown etiology and the main cause of acquired heart disease among children in the developed world. To date, abdominal involvement at presentation is not recognized as a risk factor for a more severe form of the disease. Objective To evaluate whether presenting abdominal manifestations identify a group at major risk for Intravenous immunoglobulin (IVIG)-resistance and coronary lesions. Methods Retrospective study of KD patients diagnosed between 2000 and 2015 in 13 pediatric units in Italy. Patients were divided into 2 groups according to the presence or absence of abdominal manifestations at onset. We compared their demographic and clinical data, IVIG-responsiveness, coronary ectasia/aneurysms, laboratory findings from the acute and subacute phases. Results 302 patients (181 boys) were enrolled: 106 patients with, and 196 patients without presenting abdominal features. Seasonality was different between the groups (p = 0.034). Patients with abdominal manifestations were younger (p = 0.006) and more frequently underwent delayed treatment (p = 0.014). In the acute phase, patients with abdominal presentation had higher platelet counts (PLT) (p = 0.042) and lower albuminemia (p = 0.009), while, in the subacute phase, they had higher white blood cell counts (WBC) and PLT (p = 0.002 and p < 0.005, respectively) and lower red blood cell counts (RBC) and hemoglobin (Hb) (p = 0.031 and p 0.009). Moreover, the above mentioned group was more likely to be IVIG-resistant (p < 0.005) and have coronary aneurysms (p = 0.007). In the multivariate analysis, presenting abdominal manifestations, age younger than 6 months, IVIG- resistance, delayed treatment and albumin concentration in the acute phase were independent risk factors for coronary aneurysms (respectively p<0.005, <0.005, = 0.005 and 0.009). Conclusions This is the first multicenter report demonstrating that presenting gastrointestinal features in KD identify patients at higher risk for IVIG-resistance and for the development of coronary aneurysms in a predominantly Caucasian population.


2018 - I sintomi che non ti aspetti [Articolo su rivista]
Cattini, Umberto; Loizzo, Vitaliana; Cappella, Michela; Amarri, Sergio; Iughetti, Lorenzo
abstract


2018 - IPERTENSIONE POLMONARE IN INCONTINENTIA PIGMENTII [Articolo su rivista]
Malmusi, G.; Lucaccioni, L.; Rossi, K.; Iughetti, L.; Ferrari, F.
abstract

La vasculopatia polmonare alla base della ITPS nel neonato sia stata efficacemente contrastata dalla terapia combinata con bosentan e sildenafil, suggerendo che l’inibizione dell’endotelina 1 (ET-1), possa controvertire la patogenesi della ITPS.


2018 - LA MENINGITE NEL NEONATO E NEL PICCOLO LATTANTE [Articolo su rivista]
Bedetti, L.; Baraldi, A.; Leone, Federica; Marrozzini, L.; Iughetti, L.; Lucaccioni, L.; Berardi, A.
abstract

Bacterial meningitis may cause long term disabilities or death, particularly at younger ages. Early diagnosis and prompt antibiotic therapy are essential for improving outcome. The diagnosis of meningitis in newborns and young infants is a challenge because symptoms and signs are frequently vague and non-specific, in particular at the onset of the disease. Cerebrospinal fluid culture and analysis remain nowadays the gold standard for diagnosis. Clinicians often defer lumbar puncture because of concerns of complications, although data concerning the risks of lumbar puncture at younger ages are poorly defined. Perhaps a combination of laboratory markers and selected clinical symptoms at the onset of meningitis would identify neonates with higher risk of meningitis who should necessarily undergo lumbar puncture. Currently, clinicians should be aware that the advantage of an early diagnosis of meningitis through lumbar puncture overcomes the risks related to the procedure.


2018 - L’ecografia polmonare per il pediatra [Articolo su rivista]
Giuseppe, Gallo; Fontijn, Simone; Elena, Proietti; Giulia, Cangiano; Matteo, Giuliari; Lucianer, Valeria; Francesca, Sorrentino; Grazia, Dinnella; Iughetti, Lorenzo; Ugo, Pradal
abstract

The lung ultrasound is object of a strong interest and in the lasts years there has been a huge increase in the number of publications on the topic. Its simplicity of use and learning are ensuring it an increasingly widespread use. If compared to the chest radiograph, the most used imaging technique in pediatric pulmonology, lung ultrasound appears very promising. In this article we aim to provide some basic information on lung ultrasound that can become an important start point for understanding this innovative technique.


2018 - Male or Female? What about disorders of sex development [Articolo su rivista]
Lucaccioni, L; Boncompagni, A; Pietrella, E; Ceccarelli, Pl; Ferrari, F; Berardi, A; Iughetti, L.
abstract

After the first trimester of pregnancy future parents are commonly asked if their child will be male or female. Such a question creates many expectations and implies the true determination of the baby's identity. Indeed, since the earliest stages of pregnancy knowing the gender of unborn babies creates expectations in their families, which grow with the approach of childbirth. Babies born with atypical genitalia, which consequently makes impossible to address whether they are really the same as they had been imagined, create considerable difficulties in their parents, who see their believes undermined. The evaluation of infants' genitalia, taken for granted when referring to genitalia phenotypically in the standard and often not reported for brevity in the first clinical examination after birth, becomes fundamental in case of atypia. In order to be able to take best care of such children, it is necessary to know how the hypothalamus-pituitary-gonad axis and the consequent genital development work and to understand, whenever possible, what the problem was to be able to build the best plan to support families and patients.


2018 - Phenotype and genotype of 87 patients with Mowat-Wilson syndrome and recommendations for care [Articolo su rivista]
Ivanovski, Ivan; Djuric, Olivera; Caraffi, Stefano Giuseppe; Santodirocco, Daniela; Pollazzon, Marzia; Rosato, Simonetta; Cordelli, Duccio Maria; Abdalla, Ebtesam; Accorsi, Patrizia; Adam, Margaret P; Ajmone, Paola Francesca; Badura-Stronka, Magdalena; Baldo, Chiara; Baldi, Maddalena; Bayat, Allan; Bigoni, Stefania; Bonvicini, Federico; Breckpot, Jeroen; Callewaert, Bert; Cocchi, Guido; Cuturilo, Goran; De Brasi, Daniele; Devriendt, Koenraad; Dinulos, Mary Beth; Hjortshøj, Tina Duelund; Epifanio, Roberta; Faravelli, Francesca; Fiumara, Agata; Formisano, Debora; Giordano, Lucio; Grasso, Marina; Grønborg, Sabine; Iodice, Alessandro; Iughetti, Lorenzo; Kuburovic, Vladimir; Kutkowska-Kazmierczak, Anna; Lacombe, Didier; Lo Rizzo, Caterina; Luchetti, Anna; Malbora, Baris; Mammi, Isabella; Mari, Francesca; Montorsi, Giulia; Moutton, Sebastien; Møller, Rikke S; Muschke, Petra; Nielsen, Jens Erik Klint; Obersztyn, Ewa; Pantaleoni, Chiara; Pellicciari, Alessandro; Pisanti, Maria Antonietta; Prpic, Igor; Poch-Olive, Maria Luisa; Raviglione, Federico; Renieri, Alessandra; Ricci, Emilia; Rivieri, Francesca; Santen, Gijs W; Savasta, Salvatore; Scarano, Gioacchino; Schanze, Ina; Selicorni, Angelo; Silengo, Margherita; Smigiel, Robert; Spaccini, Luigina; Sorge, Giovanni; Szczaluba, Krzysztof; Tarani, Luigi; Tone, Luis Gonzaga; Toutain, Annick; Trimouille, Aurelien; Valera, Elvis Terci; Vergano, Samantha Schrier; Zanotta, Nicoletta; Zenker, Martin; Conidi, Andrea; Zollino, Marcella; Rauch, Anita; Zweier, Christiane; Garavelli, Livia
abstract

Mowat-Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to better delineate the phenotype, natural history, and genotype-phenotype correlations of MWS.MethodsIn a collaborative study, we analyzed clinical data for 87 patients with molecularly confirmed diagnosis. We described the prevalence of all clinical aspects, including attainment of neurodevelopmental milestones, and compared the data with the various types of underlying ZEB2 pathogenic variations.ResultsAll anthropometric, somatic, and behavioral features reported here outline a variable but highly consistent phenotype. By presenting the most comprehensive evaluation of MWS to date, we define its clinical evolution occurring with age and derive suggestions for patient management. Furthermore, we observe that its severity correlates with the kind of ZEB2 variation involved, ranging from ZEB2 locus deletions, associated with severe phenotypes, to rare nonmissense intragenic mutations predicted to preserve some ZEB2 protein functionality, accompanying milder clinical presentations.ConclusionKnowledge of the phenotypic spectrum of MWS and its correlation with the genotype will improve its detection rate and the prediction of its features, thus improving patient care.GENETICS in MEDICINE advance online publication, 4 January 2018; doi:10.1038/gim.2017.221.


2018 - Primary Pediatric Cutaneous T-Cell Lymphoproliferative Disorders: 3 New Cases [Articolo su rivista]
Guerzoni, Maria E; Pruccoli, Federica; Palazzi, Giovanni; Mariotti, Ilaria; Cano, Carmen; Cellini, Monica; Cesinaro, Anna M; Mataca, Ema; Iughetti, Lorenzo
abstract

Primary cutaneous lymphoproliferative disorders are a composite group of diseases with considerable differences in histopathologic, immunophenotypic, and clinical features. They are exceedingly rare in children and in the literature only few cases are reported with extremely different therapeutic approaches. Because of the rarity of cutaneous lymphomas we consider crucial to increase the knowledge of these diseases providing every single case. We present 3 pediatric cases of primary cutaneous T-cell lymphomas occurred to our center with different features and therapeutic approach.


2018 - Proximal Microdelection 16p11.2 Syndrome [Abstract in Rivista]
Leo, Francesco; Madeo, Simona Filomena; Baraldi, Alessandro; Predieri, Barbara; Stanghellini, Ilaria; Olga, Calabrese; Iughetti, Lorenzo
abstract

Clinical History and Symptoms: XX, 9.37 years, was referred to our Clinic for obesity and psycho-motor delay. Family history: Fibromyalgic mother, two maternal cousins with psycho-motor delay, paternal uncle with epilepsy and intellectual disability. Born at term from caesarean section for placental detachment after physiological pregnancy (birth weight g 1900, SGA). In the first years of life she had psychomotor retardation, episodes of affective spasms, nocturnal enuresis, aggression in case of food containment, allergic asthma in steroid therapy, DSA and language disorder (followed by territorial NPI and scholastic support), headache (negative brain MRI, no EEG anomalies, on therapy with Oxcarbazepina), mild right transmission hearing loss. XX was previously submitted to several investigations: Rx rachis (left-convex scoliotic attitude, bilateral cervical rib sketch, antiversion of the physiological lordosis), echocardiography (normal), basic hormonal blood-based were substantially normal. At physical exam height and BMI were at the upper percentiles (83° perc, SDS 0.95, TH-SDS 2.13 and 29.7 kg / m2, respectively). She showed initial signs of pubertal activation (P1-2, S2, A +/-) and several dysmorphic features: synophry, reduced intercantal distance, small mouth, acanthosis at the base of the neck, hump, lower limb valgus, fifth finger clinodactyly of right hand, relevant abdominal adipose panniculus. Diagnostic Hypothesis and I and Ii Level Investigations: We measured TSH (2,49 mcUI/ml) and FT4 (13,9 pg/ml), cortisolemia at the lower limits (2,3 mcg/dl) with normal adrenal function, prepubertal hormonal structure and initial insulin resistance (blood sugar / insulin 4.06, HOMA index 4.10); abdomen ultrasound (steatosis); fibroscan (modest fibrosis); karyotype (normal female). Diagnosis and Eventual Therapy: On the basis of dysmorphic signs microarray analysis was performed that detect a deletion of approximately 813kb in 16p11.2 arr [hg19] 16p11.2 (29.427.215-30.240.227) x1, including the deletion of 593kb responsible for Proximal Microdelection 16p11.2 syndrome. This syndrome, from contiguous genes, is characterized by delayed development and language, mild cognitive impairment, social disability (autism spectrum disorders), mild variable dysmorphism, EEG abnormalities, predisposition to obesity, vertebral anomalies. Microdeletion 16p11.2 (Group 1) explains all the clinical features presented by our patient. The presence of obesity, in absence of involvement of the gene recognized as causative of the same, suggests that the deletion in question affects a gene region involved in the predisposition to obesity, not yet described in the literature.


2018 - QUANDO LA TESTA GOVERNA IL CUORE [Articolo su rivista]
Zagni, G.; Spada, C.; Pietrella, E.; Caramaschi, E.; Bergonzini, P.; Iughetti, L.
abstract

La malformazione aneurismatica della vena di Galeno è una condizione rara (1% tra tutte le ano- malie vascolari arterovenose fetali), potenzialmente associata ad insufficienza cardiaca neonatale.


2018 - Quando l’antibiotico fa male... un caso di nefrite interstiziale acuta [Articolo su rivista]
Boncompagni, Alessandra; Crisafi, Antonella; Bianco, Valentina; Felici, Francesca; Iughetti, Lorenzo; Amarri, Sergio
abstract


2018 - Switching From Glargine to Degludec: The Effect on Metabolic Control and Safety During 1-Year of Real Clinical Practice in Children and Adolescents With Type 1 Diabetes [Articolo su rivista]
Predieri, Barbara; Suprani, Tosca; Maltoni, Giulio; Graziani, Vanna; Bruzzi, Patrizia; Zucchini, Stefano; Iughetti, Lorenzo
abstract

Background/Objective: Insulin degludec (IDeg) is an ultra-long-acting analog with less daily variability compared to other basal insulins. In this retrospective study we examined 1-year efficacy and safety of IDeg in youth with type 1 diabetes (T1D). Subjects/Methods: Thirty-seven patients [11.7 ± 4.22 years; T1D duration 4.97 ± 3.63 years; once-daily glargine (IGlar) by at least 1 year] were switched to once-daily IDeg because of glycosylated hemoglobin (HbA1c) >7.5% and/or reported physical pain at IGlar injection. Changes in HbA1c, 30-day mean fasting plasma glucose (mean FPG), daily insulin dose, and severe hypoglycemia rates were collected at basal insulin switch (T0), 3-months (T1), 6-months (T2), and 12-months (T3) after IDeg was started. Results: In patients with HbA1c >7.5% at T0 we found a decrease in HbA1c values (%) from 8.46 ± 0.53 to 7.89 ± 0.72 at T1 (p = 0.008) and 7.97 ± 0.89 at T2 (p = 0.035). At T3, 38.9% of patients had HbA1c ≤7.5%. Mean FPG levels significantly decreased at T2 (p = 0.043). In the overall study population, we documented an increase in IDeg dose (+12.5% at T3; p < 0.001) and a decrease in mealtime insulin dose (−11.6% at T3; p = 0.001) after switch. HbA1c levels were unchanged. No episode of severe hypoglycemia was reported. Conclusions: Our data in children and adolescents with T1D suggest that IDeg dose should be increased by 12% and mealtime insulin doses should be lowered by 11% for patients who previously received IGlar. IDeg might be considered useful and well tolerated and it seems to improve the glycemic control compared to IGlar, mainly in patients with poor glycemic control.


2018 - The Effect of GnRH-Analogue Therapy on the Quality of Life of Patients with Central Precocious Puberty and their Families [Abstract in Rivista]
Lucaccioni, Laura; Marisa, Pugliese; Manzotti, Elena; Bruzzi, Patrizia; Righi, Beatrice; Poluzzi, Silvia; Madeo, Simona F.; Elena, Bigi; Predieri, Barbara; Iughetti, Lorenzo
abstract

Introduction: Quality of life (QoL) is a multidimensional indicator including several functions and represents an important evaluator of patient’s health, especially in chronic diseases. Treatment with aGnRH in Central Precocious Puberty (CPP) is source of stress for patients and families. The aim of our study is to evaluate QoL and levels of therapy-related stress in patients with CPP and in their families during and after treatment. Material and Methods: 56 patients (2 males) with CPP attending a tertiary Endocrinological Outpatient Clinic in 2015 and 2016 were enrolled. The population was divided, according to their age, in 4 categories: G1: 3 patients, 4-7 years; G2: 15 patients, 8-12 years, G3: 13 patients, 13-18 years, G4: 25 patients beyond 18 years. Groups G1 and G2 were on therapy with aGnRH, G3 were off therapy, still on clinical follow up, G4 were off therapy. We also evaluated 30 controls paired for age and level of instruction. Each patient underwent 2 questionnaires: the “Pediatric Quality of Life Inventory” (PedsQL) and a tailored “ad-hoc” questionnaire to investigate self perception in CPP. Parents also underwent the latter questionnaire. Results and Discussion: No significant differences were detected comparing PedsQL scores among G1, G2 and G3 groups each others nor comparing patients and controls. A difference statistically significant was detected in the evaluation of physical functions between G2 and controls (p: 0.02). In G2 and G3 no significant association was found between the duration of treatment and the 4 functions of PedsQL. For the self perception questionnaire scores, although no significant differences among G1, G2 and G3 themselves nor between patients and their parents were detected, the scores trend showed in patients an amount of stress therapy-related increasing proportionally with age. For G4 a direct correlation was identified between duration of treatment and emotional stress, and lower scores about self-esteem were identified, referring both to the period of therapy and the period of questionnaire’s compilation. Conclusion: In CPP, from the PedsQL, it appears that therapy with aGnRH only affects QoL on physical functions. Levels of emotional stress therapy-related, detected through ad-hoc questionnaire, increase in treated patients, independently from the treatment interruption. In off-therapy patients a decreased self-esteem and an indirect correlation between emotional stress and duration of treatment were found, underlining the effect of therapy in self perception.


2018 - THE IMPACT OF SENSOR-AUGMENTED INSULIN PUMP (SAP) THERAPY ON QUALITY OF LIFE (QOL) IN CHILDREN AND ADOLESCENTS WITH TYPE 1 DIABETES (T1D) AND THEIR PARENTS [Abstract in Rivista]
Predieri, B; Boncompagni, A; Bocchi, F; Toffoli, Carlotta; Bruzzi, P; Iughetti, L
abstract

Background and Aims: Ensuring QoL while maintaining a good glycemic control is an important challenge in T1D treatment. Aim of this study was to evaluate the impact of SAP therapy on QoL in children and adolescents with T1D and their parents. Method: 125 patients (T1D duration ‡1 year;) were recruited in the study. Twenty-one out of 125 (16.8%) were on SAP by at least 1 year (11.7 – 3.5 yrs old; T1D duration = 6.6 – 3.5 yrs) while others were on MDI by T1D onset (12.5 – 3.5 yrs old; T1D duration = 5.4 – 3.5 yrs). Patients and parents filled in the PedsQLTM 3.0 Diabetes Module including diabetes symptoms, treatment barriers, treatment adherence, worry, and communication scales. Results: Patients in the SAP group reported a higher score in the ‘‘hypoglycemic’’ item of worry scale (p = 0.035) than the MDI group. Mothers in the SAP group, respect to MDI group ones, reported a lower score in both the ‘‘injection pain’’ item of treatment barriers scale (p = 0.023) and the ‘‘difficulty to control glycemia’’ item in treatment adherence scale (p = 0.009). HbA1c (p = 0.001) and fasting plasma glucose (p = 0.044) values were significantly lower in SAP group than in MDI. Conclusion: SAP seems to reduce the fear of hypoglycemia in children and adolescents with T1D and this could be important to improve glycemic control. In mothers SAP seems to increase both barriers and adherence to treatment. The impact of new technologies on QoL should be regularly evaluated because it is critical to better understand both the medical and psychological care of T1D.


2018 - The oral communications presented by the pediatric residents at the Tabiano XXVII Congress [Articolo su rivista]
Bariola, M. C.; Vaccina, E.; Lugli, L.; Iughetti, L.; Ferrari, F.
abstract


2018 - Un pianto insistente: quando la risposta è nel sangue [Articolo su rivista]
Righi, Beatrice; Ricca, Ornella Angela; Cellini, Monica; Iughetti, Lorenzo
abstract


2018 - UNA CEFALEA CHE NON TI ASPETTI: MOYAMOYA [Articolo su rivista]
Zagni, P.; Leo, F.; Loizzo, V.; Bariola, M. C.; Cingolani, G.; Iughetti, Lorenzo
abstract

La malattia di Moyamoya è una occlusione cerebrovascolare cronica a eziologia sconosciuta caratterizzata da cambiamenti steno-occlusivi nella porzione terminale della carotide interna che portano alla formazione di una rete vascolare anomala di compenso alla base dell’encefalo. I circoli compensatori collaterali danno all’angiografia il tipico aspetto a “nuvoletta di fumo” (in giapponese moyamoya). In considerazione del sempre maggior numero di pazienti con interessamento unilaterale e della progressione dei casi monolaterali verso la bilateralità, recentemente sono stati modificati i criteri diagnostici al fine di includere sia i casi mono- che bilaterali. Nei casi monolaterali la diagnosi definitiva richiede l’angiografia, mentre nei casi bilaterali è sufficiente la risonanza magnetica.


2018 - Una trombosi A-nemica [Articolo su rivista]
Amato, Maria; Leone, Federica; Caramaschi, Elisa; Iughetti, Lorenzo
abstract


2017 - A 1-year long-term study on efficacy and safety of degludec in children and adolescents with type 1 diabetes [Abstract in Rivista]
Iughetti, L.; Suprani, T.; Bruzzi, P.; Graziani, V.; Maltoni, G.; Zucchini, S.; Predieri, B.
abstract

Objectives: Degludec (IDeg) seems to improve glycemic control and to prevent hypoglycemia, respect to glargine (IGlar), in patients with type 1 diabetes (T1D). Few data have been published on IDeg effects in childhood. The aim of our study was to assess 1-year efficacy and safety of IDeg as a part of a basal-bolus (BB) therapy in children and adolescents with T1D. Methods: Forty patients (12.34.55 yrs; 24 males; 19 prepubertal; T1D duration 5.353.78 yrs; IGlar treatment by at least 1 year) were switched to once-daily IDeg because of HbA1c >7.5% or pain at IGlar injection. Insulin dose [IGlar or IDeg plus short-acting/regular at mealtime (MT)], HbA1c, FPG, BMI z-score, and severe hypoglycaemia rates were collected at baseline (T0), 3-months (T1), 6-months (T2), and 12-months (T3) after IDeg was started. Results: The switch from IGlar to IDeg allowed a longitudinal decreased of BB dose (median Δ% -3.28 at T0, -5.02 at T1, -5.36 at T2, and -4.26 at T3; ANOVA Chi Sqr.=10.4, p=0.033) mainly due to the reduction of MT dose (median Δ% -0.00 at T0, -6.06 at T1, -5.90 at T2, and -10.7 at T3; ANOVA Chi Sqr.=18.7, p< 0.001). IDeg did not significantly reduced HbA1c levels. However, in patients with HbA1c >7.5% at T0 (21 subjects) we found a longitudinal decrease in HbA1c values from 8.4% to 7.8 at T1 (p=0.005), 7.9 at T2 (p=0.031), and 8.0 at T3 (p=0.086). Moreover, 8 out 21 had HbA1c < 7.5% at T3. FPG improved by 9.5% at T2 and 3.3% at T3. BMI z-score did not change and no episode of severe hypoglycaemia was reported. Conclusions: IDeg seems to improve the glycemic control than therapy with IGlar, mainly in patients with poor glycemic control. Our results in children and adolescents suggest that the dose of IDeg should not be reduced and the MT bolus insulin appropriate replacement doses should be lowered by 11% for patients who previously received IGlar. IDeg might be considered a useful and well tolerated basal insulin also in childhood.


2017 - Acute Intermittent Porphyria in a Child with Severe Neuropathy [Articolo su rivista]
Di Pierro, Elena; Granata, Francesca; Rosafio, Cristiano; Marchini, Stefano; Guerra, Azzurra; Brancaleoni, Valentina; Iughetti, Lorenzo; Ventura, Paolo
abstract

Clinical presentation of acute intermittent porphyria before puberty is unusual. We diagnosed the non-erythroid variant form of this disease in a male child, who first presented, at the age of 6 years, with unexplained neurological symptoms and behavioural abnormalities. We also report the successful treatment, and the long-term clinical management.


2017 - BCR-ABL-specific T-cell therapy in Ph+ ALL patients on tyrosine-kinase inhibitors [Articolo su rivista]
Comoli, Patrizia; Basso, Sabrina; Riva, Giovanni; Barozzi, Patrizia; Guido, Ilaria; Gurrado, Antonella; Quartuccio, Giuseppe; Rubert, Laura; Lagreca, Ivana; Vallerini, Daniela; Forghieri, Fabio; Morselli, Monica; Bresciani, Paola; Cuoghi, Angela; Paolini, Ambra; Colaci, Elisabetta; Marasca, Roberto; Cuneo, Antonio; Iughetti, Lorenzo; Trenti, Tommaso; Narni, Franco; Foà, Robin; Zecca, Marco; Luppi, Mario; Potenza, Leonardo
abstract

Although the emergence of bone marrow (BM)-resident (p190)BCR-ABL-specific T lymphocytes has been correlated with hematologic and cytogenetic remissions in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) undergoing maintenance tyrosine-kinase inhibitor treatment, little is known about the possibility of culturing these cells ex vivo and using them in T-cell therapy strategies. We investigated the feasibility of expanding/priming (p190)BCR-ABL-specific T cells in vitro by stimulation with dendritic cells pulsed with (p190)BCR-ABL peptides derived from the BCR-ABL junctional region and alternative splicing, and of adoptively administering them to patients with relapsed disease. We report on the feasibility of producing clinical-grade BCR-ABL-specific cytotoxic T lymphocytes (CTLs), endowed with antileukemia activity, from Ph(+) ALL patients and healthy donors. We treated 3 patients with Ph(+) ALL with autologous or allogeneic (p190)BCR-ABL-specific CTLs. No postinfusion toxicity was observed, except for a grade II skin graft-versus-host disease in the patient treated for hematologic relapse. All patients achieved a molecular or hematologic complete remission (CR) after T-cell therapy, upon emergence of (p190)BCR-ABL-specific T cells in the BM. Our results show that (p190)BCR-ABL-specific CTLs are capable of controlling treatment-refractory Ph(+) ALL in vivo, and support the development of adoptive immunotherapeutic approaches with BCR-ABL CTLs in Ph(+) ALL.


2017 - BODY EMOTIONAL MAP: STRUMENTO INNOVATIVO ED UTILE PER MIGLIORARE L’ADATTAMENTO DEI GENITORI ALLA DIAGNOSI DI DIABETE DI TIPO 1 DEL LORO BAMBINO [Abstract in Atti di Convegno]
Predieri, Barbara; Nicolucci, Antonio; Cristina Alessandrelli, Maria; Pagnini, Manuela; Pintaudi, Basilio; Zani, Fabiana; Iannilli, Antonio; Ferrito, Lucia; Lucisano, Giuseppe; Iughetti, Lorenzo; Cherubini, Valentino
abstract

OBIETTIVI La comunicazione della diagnosi di diabete di tipo 1 (DM1) in un bambino rappresenta un evento traumatico per i genitori. Il raggiungimento di un buon adattamento alla malattia del proprio figlio, per poter mantenere una buona qualità della vita, è uno degli obiettivi dell’educazione terapeutica. Scopo di questo studio longitudinale è stato quello di dimostrare l’efficacia del nuovo metodo Body Emotional Map (BEM) per aiutare i genitori a superare il trauma della diagnosi di DM1 e per ottenere il miglior adattamento alla malattia. METODI Nello studio sono stati reclutati 62 genitori (29 madri, 33 padri) di 36 bambini con DM1 (11.3±3.3 anni; durata DM1 >1 anno; HbA1c=57±11 mmol/mol) che hanno partecipato ad intervento di gruppo della durata di tre giorni. Il riesame dell’evento traumatico della diagnosi di DM1 è stato eseguito attraverso il percorso BEM caratterizzato da attività di ancoraggio spaziale e temporale, ripresa del futuro, consapevolezza emotiva e discussione interattiva. La tecnica rilassante, la respirazione diaframmatica e la visualizzazione guidata sono stati utilizzati da 1 psicologo, 1 counselor e 1 diabetologo pediatra. I questionari autosomministrati [Diabetes Related Distress (DRD), Parent Stress Index Short Form scale (PSI-SF), Fear of Hypoglycemia Survey (FHS), Parent Health Locus of Control Scale (PHLOC), e Health Survey Short Form-36 (SF-36)] sono stati compilati dai genitori al baseline, 1 mese (M1) e 3 mesi (M3) dopo l’intervento BEM. RISULTATI Rispetto al baseline, al tempo M3 abbiamo dimostrato una riduzione statisticamente significativa dei punteggi dell’item “bambino difficile” nel questionario PSI-SF (p<0.05) in entrambi i genitori, del DRD nelle madri (59.0±2.6 vs. 52.4±2.7, p=0.03) e dell’item “distress parentale” nel questionario PSI-SF nei padri (24.9±1.5 vs. 21.8±1.5, p=0.04). Inoltre, il punteggio dell’item “funzionamento sociale” nel questionario SF-36 è migliorato in modo statisticamente significativo nei padri al tempo M1 (81.3±3.2 vs. 88.3±3.2, p=0.03). CONCLUSIONI Nel DM1 dobbiamo sempre tenere in considerazione la reazione emotiva che si verifica allorquando viene comunicata la diagnosi, sia nei bambini che nei genitori. Il percorso BEM sembra essere uno strumento innovativo ed utile per ridurre lo stress e migliorare il funzionamento sociale dei genitori di bambini e adolescenti con DM1.


2017 - CASO CLINICO: QUANDO LA RISPOSTA ALLA DIETA IPOLIPIDEMIZZANTE DETERMINA LA DIAGNOSI [Abstract in Atti di Convegno]
Bruzzi, Patrizia; Predieri, Barbara; Madeo, Simona Filomena; Cattini, Umberto; Rabacchi, Claudio; Tarugi, Patrizia Maria; CALANDRA BUONAURA, Sebastiano; Iughetti, Lorenzo
abstract

PRESENTAZIONE DEL CASO, STORIA CLINICA E SINTOMATOLOGIA G.M., maschio di 7.8 anni, è stato condotto presso il centro di Dislipidemie in età evolutiva per il riscontro occasionale di ipercolesterolemia [colesterolo totale (CT) 524 mg/dl, LDL-colesterolo (LDL-C) 412 mg/dl, HDL-colesterolo (HDL-C) 52 mg/dl, trigliceridi (TG) 55 mg/dl, Apolipoproteina A (ApoA) 104 mg/dl, ApoB100 253 mg/dl]. Obiettivamente: altezza -2.02 SDS e BMI -1.40 SDS; non riscontro clinico di xantomi e/o xantelasmi, arco corneale o splenomegalia. Anamnesi patologica remota: muta. Anamnesi familiare: positiva per moderata ipercolesterolemia paterna (CT 242 mg/dl), obesità ed ipertensione. IPOTESI DIAGNOSTICHE E INDAGINI DI I E II LIVELLO Previa esclusione di una forma di ipercolesterolemia secondaria (glicemia, funzionalità tiroidea ed epato-renale nella norma), nel sospetto di ipercolesterolemia familiare omozigote abbiamo eseguito l’analisi genetica dei geni LDL-R ed ARH, risultata negativa per mutazioni. L’ecocardiografi a non documentava alterazioni. DIAGNOSI ED EVENTUALE TERAPIA In considerazione dell’iniziale assetto lipidico, abbiamo posto immediata indicazione di seguire una dieta ipolipidemizzante come da National Cholesterol Education Program ATP III - STEP II (apporto di grassi totali pari al 30% delle kcal quotidiane, grassi saturi < 7% e colesterolo < 200 mg/die). La rivalutazione dell’assetto lipidico, eseguita a distanza di 6 mesi dall’inizio della dietoterapia esclusiva, ha documentato un importante e rapido miglioramento dei valori di CT (203 mg/dl; -39%) e LDL-C (141 mg/dl; -34%). Per questo motivo abbiamo posto il sospetto diagnostico di sitosterolemia. La sitosterolemia rappresenta un disordine raro (circa 80-100 casi descritti nel mondo) a trasmissione autosomica recessiva caratterizzato da iperassorbimento intestinale e ridotta escrezione biliare di steroli vegetali. Nel nostro paziente abbiamo, quindi, dosato le concentrazioni di steroli vegetali plasmatici (mg/L) che sono risultate elevate (betasitosterolo 228, campesterolo 77.9 e desmosterolo 2.13) ed eseguito l’analisi genetica del gene ABCG8 che ha confermato il sospetto diagnostico, identifi cando la presenza di 2 mutazioni non-senso (esone 3: c.320C>G, p.Ser107*; esone 7: c.1083 G>A, p.Trp361*) come da eterozigosi composta. In considerazione della diagnosi di sitosterolemia confermata geneticamente, abbiamo posto indicazione a seguire un approccio dietetico con restrizione di cibi ad alto contenuto di steroli (olii vegetali, margarina, frutta secca, avocado, cioccolato…) associato ad un’appropriata supplementazione vitaminica.


2017 - CASO CLINICO: SINDROME DA MICRODELEZIONE 16p11.2 PROSSIMALE [Abstract in Atti di Convegno]
Mazzoni, Silvia; Madeo, Simona Filomena; Cattelani, Chiara; Stanghellini, Ilaria; Predieri, Barbara; Calabrese, Olga; Iughetti, Lorenzo
abstract

IPOTESI DIAGNOSTICHE E INDAGINI DI I E II LIVELLO Sono stati eseguiti: esami ematici che mostravano TSH ed FT4 normali, cortisolemia ai limiti inferiori con funzionalità surrenalica normale, assetto prepubere ed iniziale resistenza insulinica all’OGTT (glicemia/insulina 4.06, HOMA index 4.10); ecografi a addome (steatosi); fi broscan (fi brosi modesta); cariotipo (femminile normale). DIAGNOSI ED EVENTUALE TERAPIA A completamento diagnostico, veniva eseguita analisi microarray che rilevava una delezione di circa 813kb in 16p11.2 arr[hg19] 16p11.2(29,427,215-30,240,227)x1, comprendente la delezione di 593kb responsabile della sindrome da Microdelezione 16p11.2 Prossimale. Tale sindrome, da geni contigui, è caratterizzata da ritardo dello sviluppo e del linguaggio, deficit cognitivo lieve, disabilità sociale (disturbi dello spettro autistico), lievi dismorfismi variabili, anomalie all‘EEG, predisposizione all’obesità, anomalie vertebrali. La microdelezione 16p11.2 (Gruppo 1) spiega tutte le caratteristiche cliniche presentate dalla nostra paziente. La presenza di obesità, in assenza del coinvolgimento del gene riconosciuto come causativo della stessa, fa presupporre che la delezione in questione interessi una regione genica implicata nella predisposizione all’obesità, non ancora descritta in letteratura.


2017 - Central Precocious Puberty and Response to GnRHa Therapy in Children with Cerebral Palsy and Moderate to Severe Motor Impairment: Data from a Longitudinal, Case-Control, Multicentre, Italian Study [Articolo su rivista]
Bruzzi, Patrizia; Messina, Maria Francesca; Bartoli, Alessandra; Predieri, Barbara; Lucaccioni, Laura; Madeo, Simona Filomena; Verrotti, Alberto; De Luca, Filippo; Iughetti, Lorenzo
abstract

Children affected by neurodevelopmental disability could experience early pubertal changes at least 20 times more than the general population. Limited data about central precocious puberty (CPP) among children affected by cerebral palsy (CP) are available. Methods. This is a longitudinal, observational, retrospective, case-control study involving 22 children affected by CPP and CP (group A), 22 paired with CP but without CPP (group B), and 22 children with CPP without CP. Auxological, biochemical, and instrumental data were collected at diagnosis of CPP and at 2 follow-up visits. Results. No differences were detected between groups A (at baseline) and B. At diagnosis of CPP, height SDS adjusted for target height (H-TH SDS) was significantly reduced in A than in C (−0.63 ± 1.94 versus 1.56 ± 1.38), while basal LH and oestradiol levels were significantly elevated in A than in C. During follow-up, despite an effective treatment, growth impairment deteriorated in A than in C (Δ H-SDS from diagnosis of CPP to last follow-up: −0.49 ± 0.91 versus 0.21 ± 0.33, p = 0 023). Conclusions. Diagnosis of CPP could be partially mislead in CP due to growth failure that got worse during follow-up despite therapy. CPP in CP seems to progress rapidly along time supporting the hypothesis of a more intense activation of hypothalamic-pituitarygonadal- axis in these patients.


2017 - Challenges in the development and growth of small for gestational age newborns [Articolo su rivista]
Iughetti, Lorenzo; Lucaccioni, Laura; Ferrari, Fabrizio.
abstract

Introduction: Being born with low birth weight (less than 2.500 gr) is considered a public health problem, with an overall world rate of about 14%. Low birth weight may result from a premature birth (< 37 weeks of gestation), from several causes of intra-uterine growth restriction or from a combination of both. Areas covered: We described how, if weight and/or length at birth are not adequate for gestational age, the newborn is considered ‘small for gestational age’ and may present several growth, hormonal and developmental peculiarities, possibly due to the growth restriction developed during pregnancy. Expert commentary: We provide a description of the possible mid-term consequences of being born small for gestational age and how to follow and provide care for these babies from a multidisciplinary point of view.


2017 - COMPLICANZE MACROVASCOLARI E MORTALITÀ NEL DIABETE TIPO 1 [Abstract in Atti di Convegno]
Predieri, Barbara; Bruzzi, Patrizia; Madeo, Simona F.; Iughetti, Lorenzo
abstract

Il diabete mellito è un disturbo metabolico ad eziologia multipla, caratterizzato da iperglicemia cronica dovuta ad una difettosa secrezione o azione (o entrambi) della insulina. Le complicanze che tale condizione implica possano essere tanto dannose quanto costose. I soggetti con diabete tipo 1 (DM1), la forma di più frequente riscontro in età evolutiva, hanno un rischio da 2 a 4 volte superiore a quello della popolazione generale di sviluppare eventi aterosclerotici quali conseguenza di macroangiopatia nel lungo termine. Nello specifi co le complicanze macrovascolari del DM1 includono la malattia coronarica, la malattia vascolare periferica, e lo stroke. La prevenzione delle complicanze vascolari del diabete necessita di una rapida identificazione delle anomalie precoci. Il buon controllo glicemico ovvero il suo miglioramento sono associati ad una migliore funzionalità vascolare cardiaca e periferica. Un approccio multifattoriale che comprende anche la gestione della dislipidemia, dell’ipertensione e degli altri fattori di rischio, può essere efficace nel ridurre il tasso di eventi cardiovascolari.


2017 - CONSEGUENZE METABOLICHE A BREVE E LUNGO TERMINE IN PAZIENTI CON PUBERTÀ PRECOCE CENTRALE TRATTATI CON GNRHA IN ETÀ EVOLUTIVA: STUDIO LONGITUDINALE MONOCENTRICO [Abstract in Atti di Convegno]
Bruzzi, Patrizia; Manzotti, Elena; Elena, Bigi; Lucaccioni, Laura; Ciancia, Silvia; Righi, Beatrice; Predieri, Barbara; Iughetti, Lorenzo
abstract

OBIETTIVI In letteratura i dati disponibili sugli effetti metabolici della terapia con analoghi del GnRH (GnRHa) nei pazienti con pubertà precoce centrale (CPP) sono limitati e discordanti. Scopo dello studio è stato quello di valutare alterazioni, nel breve e nel lungo termine, dell’assetto metabolico in una coorte di pazienti con CPP trattati con GnRHa. METODI Sono stati reclutati 92 pazienti (7.49±1.21 anni; 4.3% maschi) con CPP trattati con GnRHa e seguiti nel periodo 1997-2016. Sono stati raccolti dati anamnestici, auxologici e biochimici [glicemia, insulina, homeostatic model assessment index (HOMA), glicemia/insulina ratio, colesterolo totale (TC), LDL-colesterolo (LDL-C), HDL-colesterolo (HDL-C), trigliceridi e LDL-C/HDL-C ratio] all’inizio della terapia (T0), durante la terapia (T1; follow-up medio 1.65±0.74 anni) e dopo la sua sospensione (T2; follow-up medio 8.50±4.51 anni). Per l’analisi statistica la popolazione è stata anche suddivisa in base al BMI-SDS al T0 (gruppo N, normopeso; gruppo S, sovrappeso; gruppo O, obesità). RISULTATI Considerando l’intera coorte di pazienti abbiamo dimostrato un incremento del BMI-SDS durante terapia seguito da una riduzione al T2 (T0: 0.97±1.05 vs. T1: 1.18±1.04 vs. T2: 0.63±1.20; χ2=25.4; p<0.01). Tale variazione del BMI-SDS è stata riscontrata nel gruppo N (χ2=15.8; p<0.01), mentre non è stata evidenziata nel gruppo S. Nel gruppo O abbiamo dimostrato una riduzione del BMI-SDS al T2 sia rispetto T0 sia T1 (χ2=14.8; p<0.01). L’analisi di correlazione ci ha permesso di evidenziare una correlazione statisticamente signifi cativa tra BMI-SDS al T2 e BMI-SDS al T0 (r=0.70, p<0.01) e con l’età all’inizio della terapia (r=-0.30, p<0.01). L’analisi di regressione multipla, ha identifi cato il BMI-SDS al T0 come unico fattore predittivo positivo indipendente del BMI-SDS al T2 (β 0.93, SE 0.09, p<0.01). Nella popolazione totale di pazienti, l’assetto lipidico è migliorato dopo la sospensione della terapia con GnRHa (TC: 156.5±28.7 vs.162.8±28.6 vs.149.6±23.2 mg/dl, χ2=7.97, p=0.01; LDL-C/HDL-C ratio 1.57±0.55 vs. 2.07±0.77 vs. 1.62±0.62, χ2=10.70, p<0.01). L’assetto glucidico non si è modificato durante i tempi di studio. CONCLUSIONI Nei bambini con CPP, l’effetto metabolico negativo della terapia con GnRHa sembra essere moderato e reversibile nel tempo dopo la sospensione. Il peggioramento del BMI-SDS durante la terapia risulta più evidente nei pazienti inizialmente normopeso.


2017 - Detection of Fusarium-specific T cells in hematologic patients with invasive fusariosis [Articolo su rivista]
Vallerini, Daniela; Forghieri, Fabio; Lagreca, Ivana; Riva, Giovanni; Barozzi, Patrizia; Quadrelli, Chiara; Morselli, Monica; Bresciani, Paola; Cuoghi, Angela; Coluccio, Valeria; Maccaferri, Monica; Paolini, Ambra; Colaci, Elisabetta; Marasca, Roberto; Narni, Franco; Cellini, Monica; Beauvais, Anne; Latgè, Jean Paul; Romani, Luigina; Iughetti, Lorenzo; Comoli, Patrizia; Campioli, Daniele; Trenti, Tommaso; Luppi, Mario; Potenza, Leonardo
abstract

N.A.


2017 - Diabete tipo 2 e obesità pediatrica: rassegna a cura dei Gruppi di Studio Obesità Infantile e Diabete della Società Italiana di Endocrinologia e Diabetologia Pediatrica [Articolo su rivista]
Valerio, G.; Licenziati, M. R.; Barbetti, F.; Blasetti, A.; Bruzzese, M.; Buono, P.; Cardella, F.; Cerutti, F.; D’Annunzio, G.; Di Bonito, P.; Iafusco, D.; Iughetti, L.; Maffeis, C.; Manco, M.; Miraglia del Giudice, E.; Morandi, A.; Mozzillo, E.; Predieri, B.; Schiaffini, R.; Street, M. E.; Lombardo, F.; Rabbone, I.; e Diabetologia Pediatrica, Società Italiana di Endocrinologia
abstract

L’obesità pediatrica è una condizione a elevato rischio di alterazioni del metabolismo glicidico, che con il tempo possono evolvere in diabete tipo 2 (T2D). Tali condizioni, prevalentemente caratterizzate in età pediatrica da alterata glicemia a digiuno e/o ridotta tolleranza al glucosio, sono definite come “prediabete”. Un panel di esperti dei gruppi di studio Obesità Infantile e Diabete della Società Italiana di Endocrinologia e Diabetologia pediatrica ha condotto una revisione delle più recenti evidenze scientifiche sulla condizione di prediabete e di diabete tipo 2 nell’obesità pediatrica. In questa rassegna sono descritti i fattori di rischio del prediabete e del T2D, l’epidemiologia, la diagnosi, il trattamento, le complicanze associate e la prevenzione. La prevenzione e la cura dell’obesità pediatrica rappresentano obiettivi di fondamentale importanza al fine di ridurre le alterazioni del metabolismo glicidico associate. Studi futuri dovranno identificare marcatori predittivi di T2D, in aggiunta al dato anamnestico della familiarità, che rimane di grande supporto per tale diagnosi.


2017 - Effect of Weight Loss on Markers of Inflammation and Endothelial Function in Childhood Obesity [Articolo su rivista]
Iezzi, Maria Laura; Bruzzi, Patrizia; Predieri, Barbara; Iughetti, Lorenzo
abstract

Background: Obesity is associated with chronic low-grade inflammation and hyperinsulinism that may influence the progression of endothelial dysfunction and atherosclerosis already in childhood. Methods: To study changes in metabolic profile and markers of inflammation and endothelial activation in children with primary severe obesity after weight loss we involved 14 obese children (Ob) that underwent a lifestyle intervention and 18 normal weighted subjects (C). In Ob, anthropometric data were assessed both at baseline and after intervention together with oral glucose tolerance test and fasting evaluation of cholesterol assessment, interleukin-6, endogenous secretory receptor of advanced glycation end products and endothelin levels. Results: At baseline, serum IL-6 concentrations resulted significantly higher in Ob respect to C (12.96 ± 8.87 vs.4.88 ± 1.19 pg/ml, p<0.05). After weight loss, Ob significantly improved glucose metabolism and lipid assessment and they showed a significant reduction of all markers of inflammation and endothelial activation. In all subjects studied, BMI-SDS correlated positively with interleukin-6 (r 0.45, p<0.05). Conclusion: Our results demonstrated higher concentrations of inflammatory markers in obese children compared to healthy subjects. Nevertheless, an early lifestyle intervention could improve the levels of these molecules together with cholesterol and glucose metabolism and may reverse the development of premature endothelial dysfunction in obese children.


2017 - EFFICACIA E SICUREZZA DI DEGLUDEC NEI BAMBINI ED ADOLESCENTI CON DIABETE DI TIPO 1 [Abstract in Atti di Convegno]
Predieri, Barbara; Bruzzi, Patrizia; Bonvicini, Federico; Poluzzi, Silvia; Maltoni, Giulio; Graziani, Vanna; Suprani, Tosca; Zucchini, Stefano; Iughetti, Lorenzo
abstract

OBIETTIVI L’insulina Degludec (IDeg) è un nuovo analogo lento basale che negli adulti con diabete di tipo 1 (DM1) ha permesso di ottenere valori glicemici più bassi ed un minor numero di episodi di ipoglicemia rispetto all’insulina Glargine (IGlar). Gli studi pubblicati in letteratura sugli effetti di IDeg nei soggetti in età evolutiva sono pochi. Scopo di questo studio è stato quello di valutare effi cacia e sicurezza di IDeg in bambini ed adolescenti con DM1. METODI Sono stati reclutati 20 pazienti con DM1 (15.1±4.0 anni; 9 maschi, 7 prepuberi; durata DM1 7.2±3.7 anni; IGlar ≥1 anno) in cui è stato cambiato l’analogo lento basale, passando dall’iniezione giornaliera di IGlar a quella di IDeg. BMI-SDS, HbA1c, FPG, numero di episodi di ipoglicemia grave, e dose di insulina (UI/kg/die) [IGlar o IDeg più analogo rapido/rapida] sono stati raccolti al momento dello switch da IGlar a IDeg (T0), a 3 (T1) e 6 mesi (T2) dall’inizio di IDeg. RISULTATI Abbiamo dimostrato, longitudinalmente, una riduzione statisticamente signifi cativa della dose di insulina basal-bolus (χ2=13.1; p=0.004), di quella prima dei pasti (χ2=8.68; p=0.033) e di IDeg (χ2=10.1; p=0.018). La riduzione della dose di insulina basal-bolus è risultata essere determinata dal calo della dose di insulina prima dei pasti (-9.63% a T2), piuttosto che da quello di IDeg (-2.96% a T1). I livelli di HbA1c non sono migliorati (χ2=1.66; p=0.435), tuttavia, rispetto a T0, abbiamo riscontrato una riduzione del valore di 0.35% punti al T1 e di 0.20% punti al T2. FPG è risultato signifi cativamente diminuito al T1 (-18.6±34.1 mg/dl, p=0.05). Il passaggio da IGlar ad IDeg non ha determinato signifi cative modifi che del BMI-SDS ovvero nessun episodio di ipoglicemia grave. CONCLUSIONI Rispetto a quanto riscontrato in età adulta, i nostri dati suggeriscono che in età evolutiva il passaggio da IGlar ad IDeg dovrebbe prevedere una riduzione del 5% della dose di analogo lento basale e del 10% della dose di insulina ai pasti. IDeg sembra migliorare il controllo glicemico, riducendo sia la glicemia a digiuno che l’HbA1c in assenza di complicanze acute. IDeg può essere considerata utile e ben tollerata anche nei bambini ed adolescenti con DM1.


2017 - Efficacy and Safety of Degludec in Children and Adolescents with Type 1 Diabetes [Abstract in Rivista]
Iughetti, Lorenzo; Bruzzi, Patrizia; Maltoni, Giulio; Zucchini, Stefano; Graziani, Vanna; Suprani, Tosca; Predieri, Barbara
abstract

Objectives: Insulin degludec (IDeg) is a new basal insulin. Few data have been published on IDeg effects in childhood. Our purpose was to assess the efficacy and the safety of IDeg in children and adolescents with type 1 diabetes (T1D). Methods: Thirtyseven patients (12.6±4.89 yrs; 21 males; T1D duration 5.50±3.92 yrs; IGlar treatment at least 1 year) were switched to IDeg once daily. z-score BMI, HbA1c, FPG, severe hypoglycaemia rates, and insulin dose [IGlar or IDeg plus short-acting/regular] were collected at baseline (T0, during IGlar treatment), 3 months (T1), and 6 months (T2) after IDeg was started. Results: The switch from IGlar to IDeg allowed a longitudinal dose change of basal insulin (median -4.45% at T0, -0.77 at T1, and -1.53 ant T2; ANOVA Chi Sqr.=9.49, p=0.023) with a significant reduction of short-acting/regular mealtime (MT) (p=0.002) insulin. Despite the lack of statistical significance, mean HbA1c decreased from 7.6% to 7.3% (T1) and 7.4% (T2). FPG improved by 9.5% after 6-months. z-score BMI did not change and no episode of severe hypoglycaemia was reported. Conclusions: IDeg seems to improve the glycemic control than therapy with IGlar. Despite data from adults with T1D, our results in childhood suggest that the dose of IDeg should not be reduced and the MT bolus insulin appropriate replacement doses should be lowered by 8% for patients who previously received IGlar. IDeg might be considered a useful and well tolerated basal insulin also in childhood.


2017 - Familial hypercholesterolemia: The Italian Atherosclerosis Society Network (LIPIGEN) [Articolo su rivista]
Averna, Maurizio; Cefalã¹, Angelo B.; Casula, Manuela; Noto, Davide; Arca, Marcello; Bertolini, Stefano; Calandra, Sebastiano; Catapano, Alberico L.; Tarugi, Patrizia; Arca, Marcello; Averna, Maurizio; Bertolini, Stefano; Calandra, Sebastiano; Catapano, Alberico Luigi; Tarugi, Patrizia; Pellegatta, Fabio; Angelico, Francesco; Arca, Marcello; Averna, Maurizio; Bartuli, Andrea; Biasucci, Giacomo; Biolo, Gianni; Bonanni, Luca; Bonomo, Katia; Borghi, Claudio; Bossi, Antonio Carlo; Branchi, Adriana; Carubbi, Francesca; Cipollone, Francesco; Citroni, Nadia; Federici, Massimo; Ferri, Claudio; Fiorenza, Anna Maria; Giaccari, Andrea; Giorgino, Francesco; Guardamagna, Ornella; Iannuzzi, Arcangelo; Iughetti, Lorenzo; Lupattelli, Graziana; Mandraffino, Giuseppe; Marcucci, Rossella; Mombelli, Giuliana; Muntoni, Sandro; Pecchioli, Valerio; Pederiva, Cristina; Pipolo, Antonio; Pisciotta, Livia; Pujia, Arturo; Purrello, Francesco; Repetti, Elena; Rubba, Paolo; Sabbã , Carlo; Sampietro, Tiziana; Sarzani, Riccardo; Tagliabue, Milena Paola; Trenti, Chiara; Vigna, Giovanni Battista; Werba, Josà Pablo; Zambon, Sabina; Zenti, Maria Grazia; Montali, Anna; Noto, Davide; Bertolini, Stefano; Calandra, Sebastiano; Fortunato, Giuliana; Grigore, Liliana; Del Ben, Maria; Maranghi, Marianna; Cefalã¹, Angelo B.; Barbagallo, Carlo M.; Buonuomo, Paola Sabrina; Capra, Maria Elena; Vinci, Pierandrea; D'Addato, Sergio; Galbiati, Stella; Nascimbeni, Fabio; Bucci, Marco; Spagnoli, Walter; Cardolini, Iris; Cervelli, Nazzareno; Emanuela, Colombo; Vinsin, A. Sun; Laviola, Luigi; Bello, Francesca; Chiariello, Giuseppe; Predieri, Barbara; Siepi, Donatella; Saitta, Antonino; Giusti, Betti; Pavanello, Chiara; Lussu, Milena; Prati, Lucia; Banderali, Giuseppe; Balleari, Giulia; Montalcini, Tiziana; Scicali, Roberto; Gentile, Luigi; Gentile, Marco; Suppressa, Patrizia; Sbrana, Francesco; Cocci, Guido; Benso, Andrea; Negri, Emanuele Alberto; Ghirardello, Omar; Lorenzo, Vigo; Zambon, Alberto; Enzo, Bonora; Minicocci, Ilenia; Spina, Rossella; Orlando, Camilla; Tarugi, Patrizia; Di Taranto, Maria Donata; Catapano, Alberico Luigi; Casula, Manuela; Chiodo, Lorenzo; Garlaschelli, Katia; Manzato, Enzo; Tragni, Elena
abstract

Background and aims Primary dyslipidemias are a heterogeneous group of disorders characterized by abnormal levels of circulating lipoproteins. Among them, familial hypercholesterolemia is the most common lipid disorder that predisposes for premature cardiovascular disease. We set up an Italian nationwide network aimed at facilitating the clinical and genetic diagnosis of genetic dyslipidemias named LIPIGEN (LIpid TransPort Disorders Italian GEnetic Network). Methods Observational, multicenter, retrospective and prospective study involving about 40 Italian clinical centers. Genetic testing of the appropriate candidate genes at one of six molecular diagnostic laboratories serving as nationwide DNA diagnostic centers. Results and conclusions From 2012 to October 2016, available biochemical and clinical information of 3480 subjects with familial hypercholesterolemia identified according to the Dutch Lipid Clinic Network (DLCN) score were included in the database and genetic analysis was performed in 97.8% of subjects, with a mutation detection rate of 92.0% in patients with DLCN score ≥6. The establishment of the LIPIGEN network will have important effects on clinical management and it will improve the overall identification and treatment of primary dyslipidemias in Italy.


2017 - Gli interferenti endocrini [Articolo su rivista]
Bernasconi, Sergio; Street, Maria; Predieri, Barbara; Iughetti, Lorenzo
abstract

La problematica connessa agli interferenti endocrini (IE) (Endocrine Disrupting Chemicals EDC-) è complessa perché coinvolge aspetti non solo sanitari, metodologici e di ricerca scientifica, ma ha più ampie valenze di natura sociale, economica e legislativa-normativa.


2017 - How Accurate Is a Single Cutpoint to Identify High Blood Pressure in Adolescents? [Articolo su rivista]
Brambilla, Paolo; Andreano, Anita; Antolini, Laura; Bedogni, Giorgio; Salvatoni, Alessandro; Iughetti, Lorenzo; Moreno, Luis Alberto; Pietrobelli, Angelo; Genovesi, Simonetta
abstract

In 2007 the International Diabetes Federation (IDF) proposed single blood pressure (BP) cutpoints (systolic: ≥130 mm Hg and diastolic: ≥85&nbsp;mm Hg) for the diagnosis of high blood pressure (HBP) in adolescents. Before this proposal, HBP had been defined as BP at or above the 95th percentile for age, sex, and height percentile (reference standard). In this study, we evaluated the risk for misclassification when using the IDF single-cutpoints criteria. We first applied the IDF criteria to a reconstructed population with the same age, sex, and height distribution as the population used to develop the reference standard. The proposed single cutpoints corresponded to percentiles from the 81.6th to 99.9th for systolic BP and from the 92.9th to 98.9th for diastolic BP in the reconstructed population. Using IDF criteria, there were high false-negative fractions for both systolic and diastolic BP (from 54% to 93%) in 10- to 12-year-olds and a false-positive fraction up to 35% in older subjects. We then applied the IDF criteria to 1,162 overweight/obese adolescents recruited during 1998-2000 from pediatric clinical centers in Milano, Varese, and Modena in Italy and in Zaragoza, Spain. Overall false-negative and false-positive fractions were 22% and 2%, respectively; negative predictive values were especially low for 10- to 12-year-old subjects. The use of IDF's single cutpoints carries a high risk of misclassification, mostly due to false negatives in younger subjects. The effort to simplify diagnosis could be overcome by the risk of undiagnosed HBP.


2017 - IMPATTO DELLA TERAPIA CON ANALOGO DEL GNRH SULLA QUALITÀ DELLA VITA DEI PAZIENTI CON CPP E DELLE LORO FAMIGLIE [Abstract in Atti di Convegno]
Lucaccioni, Laura; Marisa, Pugliese; Bruzzi, Patrizia; Elena, Bigi; Madeo, Simona F.; Manzotti, Elena; Rocca, Laura; Predieri, Barbara; Iughetti, Lorenzo
abstract

OBIETTIVI La qualità di vita (QoL) è un importante componente dello stato di salute del paziente ed è un indicatore delle conseguenze a lungo termine di malattia cronica. Non sussiste, tuttavia, concordanza tra gravità della malattia, trattamento e QoL. Obiettivo del nostro studio è quello di valutare la QoL dei bambini affetti da pubertà precoce centrale in trattamento con aGnRH e dopo la terapia e dei loro genitori. METODI Sono stati valutati 56 pazienti (2M) di cui 3 di età compresa fra 4-7 aa(G1), 15 fra 8-12aa(G2), 13 fra 13-18aa(G3), 25>18aa(G4) e comparati a 25 controlli(4-18 aa). Tutti sono stati sottoposti al questionario “Paediatric Quality of Life Inventory” (PedsQL) che valuta funzione fisica, emotiva, sociale, scolastica, e ad un questionario messo a punto per valutare lo stress emotivo correlato alla terapia (SET). I genitori di G1, G2, G3 sono stati sottoposti a PedsQL per le scale di funzione emotiva e sociale. RISULTATI Per tutte le scale del PedsQL non sussiste differenza significativa fra G1, G2, G3 e controlli. Dal confronto figli/genitori non emergono differenze significative nei gruppi G1(p= 0.59); G2(p=0.61); G3 (p=0.48). Inoltre, in G2 e G3 non c’è correlazione fra le 4 scale del PedsQL e durata del trattamento. Comparando SET nei quattro gruppi, si evince come sussista una differenza signifi cativa fra G2 e G4 (p=0.029) e fra G3 e G4 (p=0.011). Per i gruppi G2 e G3 la durata del trattamento non sembra essere correlata con SET né nei pazienti (p=0.94; p=0.52) né nei genitori (p=0,21; p=0.7). In G4, tuttavia, sussiste una correlazione significativa fra durata della terapia e SET (p:0.021, r 0.47). Inoltre, in G4 SET è risultato essere maggiore riferendosi al periodo del trattamento rispetto al momento di compilazione del questionario(p<0.001). CONCLUSIONI La terapia con aGnRH, valutata mediante PedsQL, non sembra inficiare la QoL sia dei pazienti in trattamento che dei loro genitori, indipendentemente dalla durata della terapia. Tuttavia è stato possibile identificare, mediante questionario specifico, come i livelli di stress emotivo siano aumentati nei pazienti in trattamento rispetto agli offtherapy e, in questi ultimi, come sussista una correlazione tra stress emotivo e durata del trattamento.


2017 - Insulin pump failures in Italian children with Type 1 diabetes: retrospective 1-year cohort study [Articolo su rivista]
Rabbone, I; Minuto, N.; Bonfanti, R.; Marigliano, M.; Cerutti, F.; Cherubini, V.; D'Annunzio, G.; Frongia, A. P.; Iafusco, D.; Ignaccolo, G.; Lombardo, F.; Schiaffini, R.; Toni, S.; Tumini, S.; Zucchini, S.; Pistorio, A.; Scaramuzza, A. E.; Lera, R.; Secco, A.; Bobbio, A.; Bechaz, M.; Piccinno, E.; Natale, M. P.; Ortolani, F.; Zecchino, C.; Lonero, A.; Maltoni, G.; Pasquino, B.; Gallo, F.; Frongia, P.; Ripoli, C.; Lo Presti, D.; Timpanaro, T.; Citriniti, F.; Suprani, T.; Carinci, S.; Cipriano, P.; Lazzaro, N.; De Donno, V.; Gallarotti, F.; Lenzi, L.; Piccini, B.; Vittorio, L.; Russo, C.; Borea, R.; Mammì, F.; Bruzzese, M.; Ventrici, C.; Salzano, G.; Frontino, G.; Bonura, C.; Favalli, V.; Scaramuzza, A.; Zuccotti, G. V.; Ferrari, M.; Iughetti, Lorenzo; Predieri, Barbara; Franzese, A.; Mozzillo, E.; Buono, P.; Confetto, S.; Zanfardino, A.; Cadario, F.; Savastio, S.; Fiorito, C.; Barbieri, P.; Piredda, G.; Cardella, F.; Ropolo, R.; Federico, G.; Marchi, B.; Benevento, D.; Carducci, C.; Mancabitti, M. L.; Del Vecchio, M.; Lapolla, R.; Gaiero, A.; Fichera, G.; Ignaccolo, M. G.; Tinti, D.; Cauvin, V.; Franceschi, R.; Biagioni, M.; Salvatoni, A.; Scolari, A.; Maffeis, C.; Sabbion, A.; Arnaldi, C.; Tosini, D.
abstract

Aims: Insulin pump failure and/or malfunction requiring replacement have not been thoroughly investigated. This study evaluated pump replacement in children and adolescents with Type 1 diabetes using insulin pump therapy. Methods: Data were collected for all participants younger than 19 years, starting insulin pump therapy before 31 December 2013. For each child, age, disease duration, date of insulin pump therapy initiation, insulin pump model, failure/malfunction/replacement yes/no and reason were considered for the year 2013. Results: Data were returned by 40 of 43 paediatric centres belonging to the Diabetes Study Group of the Italian Society of Paediatric Endocrinology and Diabetology. In total, 1574 of 11 311 (13.9%) children and adolescents with Type 1 diabetes were using an insulin pump: 29.2% Animas VIBE™, 9.4% Medtronic MiniMed 715/515™, 34.3% Medtronic MiniMed VEO™, 24.3% Accu-Check Spirit Combo™ and 2.8% other models. In 2013, 0.165 insulin pump replacements per patient-year (11.8% due to pump failure/malfunction and 4.7% due to accidental damage) were recorded. Animas VIBE™ (22.1%) and Medtronic MiniMed VEO™ (17.7%) were the most replaced. Conclusions: In a large cohort of Italian children and adolescents with Type 1 diabetes, insulin pump failure/malfunction and consequent replacement are aligned with rates previously reported and higher in more sophisticated pump models.


2017 - Interdural cavernous sinus dermoid cyst in a child: case report [Articolo su rivista]
Giordano, Flavio; Peri, Giacomo; Bacci, Giacomo M; Basile, Massimo; Guerra, Azzurra; Bergonzini, Patrizia; Buccoliero, Anna Maria; Spacca, Barbara; Iughetti, Lorenzo; Donati, Pierarturo; Genitori, Lorenzo
abstract

Interdural dermoid cysts (DCs) of the cavernous sinus (CS), located between the outer (dural) and inner layer (membranous) of the CS lateral wall, are rare lesions in children. The authors report on a 5-year-old boy with third cranial nerve palsy and exophthalmos who underwent gross-total removal of an interdural DC of the right CS via a frontotemporal approach. The patient had a good outcome and no recurrence at the 12-month follow-up. To the best of the authors' knowledge this is the second pediatric case of interdural DC described in the literature.


2017 - IPERTENSIONE IN BAMBINI ED ADOLESCENTI AFFETTI DA DIABETE DI TIPO 1: ALTA PREVALENZA IDENTIFICATA TRAMITE L’UTILIZZO DEL MONITORAGGIO PRESSORIO AMBULATORIALE [Abstract in Atti di Convegno]
Predieri, Barbara; Bruzzi, Patrizia; Berardi, Maria Gabriella; Cattelani, Chiara; Leo, Francesco; Mazzoni, Silvia; Roncuzzi, Francesca; Madeo, Simona F.; Iughetti, Lorenzo
abstract

OBIETTIVI - L’ipertensione nei bambini ed adolescenti con diabete di tipo 1 (DM1) è associata ad un aumentato rischio di complicanze cardiovascolari in età adulta. Il monitoraggio pressorio ambulatoriale (24h-ABPM) consente la registrazione dei valori pressori per 24 ore in un ambiente non medico; tuttavia, i dati sulla sua utilità in età evolutiva sono ancora controversi. Gli obiettivi di questo studio sono stati quelli di confrontare la prevalenza di ipertensione utilizzando sia il metodo oscillometrico tradizionale sia il 24h-ABPM ovvero di valutare l’utilità del 24h-ABPM nella diagnosi precoce di ipertensione al fi ne di iniziare un trattamento precoce. METODI - Sono stati reclutati 40 bambini ed adolescenti (52.5% maschi) con DM1 (13.6±2.56 anni; durata DM1 >1 anno) e raccolti dati antropometrici, metabolici (HbA1c, assetto lipidico, funzionalità renale) e pressione arteriosa (sfigmomanometro oscillometrico e 24h-ABPM). L’ipertensione è stata definita come: A) pressione arteriosa sistolica (SBP) superiore al 95° percentile per età, sesso e percentile di altezza con sfigmomanometro oscillometrico; B) SBP superiore al 95° percentile per un tempo >25% con 24h-ABPM. RISULTATI - Utilizzando lo sfigmomanometro oscillometrico durante la visita clinica, sono risultati ipertesi 9 pazienti su 40 (22.5%) mentre, tramite 24h-ABPM, la prevalenza di ipertensione è risultata significativamente maggiore (57.5%; χ2=8.58, p=0.003). I pazienti risultati ipertesi con 24h-ABPM avevano una durata di DM1 più lunga rispetto ai normotesi (8.04±3.22 vs. 5.76±1.85 anni, rispettivamente, p=0.013). Utilizzando le curve ROC abbiamo identificato i 6.5 anni dall’esordio del DM1 come cut-off predittivo di carico SBP >25% (AUC 0.716). L’analisi multivariata ha permesso di identifi care la durata della malattia (β=0.49, SE 0.17, p=0.006) ed il z-score BMI (β=0.41, SE 0.20, p=0.049) come principali fattori predittivi per il carico di SBP >95° percentile. I nostri dati non hanno supportato una relazione tra ipertensione, controllo metabolico, profilo lipidico ed indici di funzionalità renale. CONCLUSIONI - 24h-ABPM ha permesso di identificare una maggiore prevalenza di ipertensione e potrebbe essere introdotta nella comune pratica clinica a distanza di 6 anni dall’esordio del DM1. 24h-ABPM può essere considerato uno strumento utile per identificare precocemente i soggetti con ipertensione che possono beneficiare di un trattamento precoce per prevenire le complicanze renali e cardiovascolari.


2017 - Lactobacillus reuteri oral administration improves periodontal disease in children and adolescents with type 1 diabetes [Abstract in Rivista]
Predieri, B.; Cenciarelli, V.; Bruzzi, P.; Miceli, Dalila; Bonvicini, F.; Leo, F.; Forabosco, A.; Iughetti, L.
abstract

Objectives: Understanding the clinical manifestations and management of periodontal disease are important for the optimal care of patients with type 1 diabetes (T1D). Probiotics could protect the oral tissues against the action of periodontal pathogenic bacteria. We aimed to assess the effects of the administration of Lactobacillus reuteri as probiotic upon oral health in children and adolescents T1D. Methods: Forty-three patients (11.32.77 yrs.; T1D duration 58.238.0 months) were enrolled and randomly assigned to Group A (probiotic - 5 drops/day, 10^8 CFU/day for 3 months) and Group B (no probiotic). Oral health index [Full Mouth Plaque Score (FMPS), Full Mouth Bleeding Score (FMBS)], insulin dose (IU/kg/day), and HbA1c were measured at baseline (T0) and 3-months after (T1). Results: FMPS significantly improved in both Group A and B (p<0.05). In Group B daily insulin dose increased (p=0.01) and HbA1c improved (p< 0.001) at T1, while in Group A the metabolic control was unchanged. We performed a telephone survey to evaluate the probiotic compliance in Group A. 13 out 22 patients reported a regular probiotic intake (A1), while the other ones used it sporadically (A2). Despite FMPS and FMBS values were not different between groups at T0, they were significantly lower (p< 0.05) in Group A1 respect to Group A2 at T1. FMPS and FMBS longitudinally decreased in Group A1 but not in Group A2. Conclusions: Our preliminary data suggest that 3-months oral administration of probiotic might improve the oral health of children and adolescents with T1D and confirm that glycemic control have also an influence on oral health.


2017 - Le comunicazioni orali presentate dagli specializzandi al congresso Tabiano XXVI [Articolo su rivista]
Gioachin, A.; Borraccetti, N.; Sprocati, M.; Maggiore, G.; Govoni, M. R.; Procaccianti, M.; Panigari, A.; Casadio, G.; Ruberto, C.; Toffoli, C.; Zagni, G.; Mandese, V.; Roncuzzi, F.; Gavioli, S.; Gargano, G.; Iughetti, L.; Norato, A.; Lembo, G.; Fiorica, L.; Davio, P.; Spezia, E.; Casciana, M. L.; Buzi, F.
abstract


2017 - L’infiltrato speciale [Articolo su rivista]
Toffoli, Carlotta; Zagni, Giulia; Mandese, Valentina; Roncuzzi, Francesca; Gavioli, Sara; Gargano, Giancarlo; Iughetti, Lorenzo
abstract

In letteratura, esistono pochi casi di mastocitosi cutanea a esordio neonatale, da considerare nella diagnosi differenziale delle lesioni bollose congenite. Descriviamo un caso di mastocitosi cutanea a esordio neonatale, diagnosticato clinicamente.


2017 - Lotus Birth Associated With Idiopathic Neonatal Hepatitis [Articolo su rivista]
Tricarico, Antonella; Bianco, Valentina; Iughetti, Lorenzo; Ferrari, Fabrizio; Berardi, Alberto
abstract

In the present case, the infant presented with a complication of LB. There was a close temporal relationship between LB and the onset of clinical symptoms. The baby had persistent jaundice associated with a severe increase in aspartate and alanine aminotransferases without evidence of cholestasis. Recovery occurred spontaneously after the first months of life. Hepatobiliary, hematological, metabolic, endocrine, and genetic disorders were ruled out.


2017 - MALATTIA PARODONTALE IN BAMBINI ED ADOLESCENTI CON DIABETE DI TIPO 1: EFFICACIA DELLA SOMMINISTRAZIONE ORALE DI LACTOBACILLUS REUTERI [Abstract in Atti di Convegno]
Predieri, Barbara; Cattelani, Chiara; Cenciarelli, Valentina; Mazzoni, Silvia; Russo, Giovanna; Miceli, Dalila; Forabosco, Andrea; Iughetti, Lorenzo
abstract

OBIETTIVI Nei soggetti con diabete di tipo 1 (DM1) il rischio di sviluppare malattia parodontale è fi no a 5-volte maggiore rispetto ai soggetti sani; tuttavia, in età evolutiva, le prove a sostegno dell’associazione tra queste due malattie sono controverse. La somministrazione orale di probiotici crea un biofi lm e protegge i tessuti orali contro l’azione dei batteri patogeni parodontali. Scopo di questo studio longitudinale è stato quello di valutare gli effetti della somministrazione di probiotici (Lactobacillus reuteri) sulla salute orale di bambini ed adolescenti con DM1. METODI Sono stati reclutati 43 pazienti con DM1 (11.3±2.77 anni; durata DM1 58.2±38.0 mesi) randomizzati nel Gruppo A (probiotico - 10^8 CFU/die per 3 mesi) e nel Gruppo B (senza probiotico). Al baseline (T0) e dopo 3 mesi (T1) sono stati valutati i seguenti parametri: Full Mouth Plaque Score (FMPS), Full Mouth Bleeding Score (FMBS), dose di insulina (UI/kg/die) e HbA1c. RISULTATI FMPS al T1 è migliorato sia nel Gruppo A che nel Gruppo B (p<0.05). Nel Gruppo B dal T0 al T1 abbiamo riscontrato un aumento della dose di insulina (0.77±0.17 vs. 0.83±0.18 UI/kg/die; p=0.01) ed un miglioramento dell’HbA1c (82.1±21.4 vs. 69.9±19.1 mmol/mmol; p<0.001). Il controllo metabolico non si è modifi cato nel Gruppo A. Per valutare l’aderenza alla somministrazione del probiotico nei pazienti del Gruppo A abbiamo eseguito un sondaggio telefonico: 13 pazienti su 22 hanno riferito un’assunzione regolare (Gruppo A1), mentre negli altri la compliance è risultata sporadica (Gruppo A2). Confrontando i dati di questi 2 gruppi, al T0 non abbiamo riscontrato differenze nei valori di FMPS e FMBS; al T1 entrambi gli indici sono risultati signifi cativamente inferiori (p<0.05) nel Gruppo A1 rispetto al Gruppo A2. La riduzione longitudinale di FMPS e FMBS è stata dimostrata nel Gruppo A1 (p<0.05) ma non nel Gruppo A2. Nessuna modifi ca signifi cativa della dose di insulina e di HbA1c è stata dimostrata. CONCLUSIONI I nostri dati preliminari suggeriscono che la regolare somministrazione orale di probiotici potrebbe migliorare la salute orale dei bambini e adolescenti con DM1 e confermano l’importante ruolo del controllo glicemico.


2017 - Medication-related visits in a pediatric emergency department: an 8-years retrospective analysis [Articolo su rivista]
Rosafio, Cristiano; Paioli, Serena; DEL GIOVANE, Cinzia; Cenciarelli, Valentina; Viani, Nilla; Bertolani, Paolo; Iughetti, Lorenzo
abstract

There are limited data on the characterization of medication-related visits (MRVs) to the emergency department (ED) in pediatric patients in Italy. We have estimated the frequency, severity, and classification of MRVs to the ED in pediatric patients.


2017 - Monogenic Diabetes accounts for 6.3% of cases referred to 15 Italian pediatric diabetes Centers during 2007-2012 [Articolo su rivista]
Delvecchio, Maurizio; Mozzillo, Enza; Salzano, Giuseppina; Iafusco, Dario; Frontino, Giulio; Patera, Patrizia I; Rabbone, Ivana; Cherubini, Valentino; Grasso, Valeria; Tinto, Nadia; Giglio, Sabrina; Contreas, Giovanna; Di Paola, Rosa; Salina, Alessandro; Cauvin, Vittoria; Tumini, Stefano; D'Annunzio, Giuseppe; Iughetti, Lorenzo; Mantovani, Vilma; Maltoni, Giulio; Toni, Sonia; Marigliano, Marco; Barbetti, Fabrizio
abstract

Etiologic diagnosis of diabetes may impact on therapeutic strategy, and prognosis of chronic complications.: The aim of the study was to establish the relative percentage of different diabetes subtypes in patients attending Italian pediatric diabetes centers, and the influence of etiologic diagnosis on therapy. This was a retrospective study. Clinical records of 3781 consecutive patients (age: 0-18 years) referred to fifteen pediatric diabetes clinics and diagnosed with diabetes or IFG between Jan/1/2007 and Dec/31/2012 were examined. Clinical characteristics of patients at the first time of referral to Centers, type 1 diabetes-related autoantibodies, molecular genetics records, and C-peptide measurement, if requested for etiologic diagnosis, were acquired. The primary outcome was to assess the percentage of each diabetes subtype of our sample. Type 1 diabetes represents the main cause (92.4%) of diabetes of this group of patients, followed by monogenic diabetes, that accounts for 6.3 % of cases (Maturity Onset Diabetes of the Young; MODY: 5.5%, Neonatal Diabetes Mellitus; NDM: 0.6%, genetic syndromes: 0.2%). Of interest, genetic diagnosis prompted the transfer from insulin to sulphonylureas in twelve patients bearing mutations in HNF1A or KCNJ11 genes. Type 2 diabetes was diagnosed in 1% of patients. Monogenic diabetes is highly prevalent in patients referred to Italian pediatric diabetes centers. Genetic diagnosis guided therapeutic decisions, allowed to formulate a prognosis on chronic diabetic complications in a relevant number of patients (i.e. GCK/MODY), and helped to provide genetic counseling.


2017 - Neuroimaging findings in Mowat-Wilson syndrome: a study of 54 patients [Articolo su rivista]
Garavelli, Livia; Ivanovski, Ivan; Caraffi, Stefano Giuseppe; Santodirocco, Daniela; Pollazzon, Marzia; Cordelli, Duccio Maria; Abdalla, Ebtesam; Accorsi, Patrizia; Adam, Margaret P; Baldo, Chiara; Bayat, Allan; Belligni, Elga; Bonvicini, Federico; Breckpot, Jeroen; Callewaert, Bert; Cocchi, Guido; Cuturilo, Goran; Devriendt, Koenraad; Dinulos, Mary Beth; Djuric, Olivera; Epifanio, Roberta; Faravelli, Francesca; Formisano, Debora; Giordano, Lucio; Grasso, Marina; Grønborg, Sabine; Iodice, Alessandro; Iughetti, Lorenzo; Lacombe, Didier; Maggi, Massimo; Malbora, Baris; Mammi, Isabella; Moutton, Sebastien; Møller, Rikke; Muschke, Petra; Napoli, Manuela; Pantaleoni, Chiara; Pascarella, Rosario; Pellicciari, Alessandro; Poch Olive, Maria Luisa; Raviglione, Federico; Rivieri, Francesca; Russo, Carmela; Savasta, Salvatore; Scarano, Gioacchino; Selicorni, Angelo; Silengo, Margherita; Sorge, Giovanni; Tarani, Luigi; Tone, Luis Gonzaga; Toutain, Annick; Trimouille, Aurelien; Valera, Elvis Terci; Vergano, Samantha Schrier; Zanotta, Nicoletta; Zollino, Marcella; Dobyns, William B; Paciorkowski, Alex R.
abstract

Mowat–Wilson syndrome (MWS) is a genetic disease characterized by distinctive facial features, moderate to severe intellectual disability, and congenital malformations, including Hirschsprung disease, genital and eye anomalies, and congenital heart defects, caused by haploinsufficiency of the ZEB2 gene. To date, no characteristic pattern of brain dysmorphology in MWS has been defined. Through brain magnetic resonance imaging (MRI) analysis, we delineated a neuroimaging phenotype in 54 MWS patients with a proven ZEB2 defect, compared it with the features identified in a thorough review of published cases, and evaluated genotype–phenotype correlations. Ninety-six percent of patients had abnormal MRI results. The most common features were anomalies of corpus callosum (79.6% of cases), hippocampal abnormalities (77.8%), enlargement of cerebral ventricles (68.5%), and white matter abnormalities (reduction of thickness 40.7%, localized signal alterations 22.2%). Other consistent findings were large basal ganglia, cortical, and cerebellar malformations. Most features were underrepresented in the literature. We also found ZEB2 variations leading to synthesis of a defective protein to be favorable for psychomotor development and some epilepsy features but also associated with corpus callosum agenesis. This study delineated the spectrum of brain anomalies in MWS and provided new insights into the role of ZEB2 in neurodevelopment.


2017 - Omitting duodenal biopsy in children with suspected celiac disease and extra-intestinal symptoms [Articolo su rivista]
Bozzola, Mauro; Meazza, Cristina; Gertosio, Chiara; Pagani, Sara; Larizza, Daniela; Calcaterra, Valeria; Luinetti, Ombretta; Farello, Giovanni; Tinelli, Carmine; Iughetti, Lorenzo
abstract

The aim of our study is to evaluate if in children with highly positive serology and HLA-DQ2/DQ8 (triple test, TT) and only extra-intestinal symptoms, it is possible to omit performing an intestinal biopsy for celiac disease (CD) diagnosis, as suggested by the new European Society for Pediatric Gastroenterology, Hepatology and Nutrition ESPGHAN guidelines.


2017 - Oral Administration of Lactobacillus Reuteri Improves Periodontal Disease in Children and Adolescents with Type 1 Diabetes [Abstract in Rivista]
Predieri, Barbara; Barbieri, Sara; Miceli, Dalila; Cattelani, Chiara; Mazzoni, Silvia; Forabosco, Andrea; Iughetti, Lorenzo
abstract

Objectives: There is disagreement on the effect of diabetes on oral hygiene. Probiotics creating a biofilm could protect the oral tissues against periodontal bacteria. We aimed to assess the effects of Lactobacillus reuteri administration upon the oral health of children and adolescents with type 1 diabetes (T1D). Methods: Forty-three patients (11.3±2.77 yrs.; T1D duration 58.2±38.0 months) were enrolled and randomly assigned to Group A (probiotic - 10^8 CFU/day for 3 months) and Group B (no probiotic). Full Mouth Plaque Score (FMPS), Full Mouth Bleeding Score (FMBS), insulin dose (IU/kg/day), and HbA1c were measured at baseline (T0) and 3-months after (T1). Results: FMPS significantly improved in both Group A and B (p<0.05). In Group B insulin dose increased (p=0.01) and HbA1c improved (p<0.001) at T1; in Group A the metabolic control was unchanged. In Group A, 13 out 22 patients reported a regular probiotic intake (Group A1), while the other ones used it sporadically (Group A2). Despite FMPS and FMBS values were not different between groups at T0, they were significantly lower (p<0.05) in Group A1 respect to Group A2 at T1 and longitudinally decreased in Group A1 but not in Group A2. Conclusions: Our preliminary data suggest that 3-months administration of probiotic might improve the oral health of children and adolescents with T1D and confirm the influence of the glycemic control.


2017 - Sleep habits and pattern in 1-14 years old children and relationship with video devices use and evening and night child activities [Articolo su rivista]
Brambilla, Paolo; Giussani, Marco; Pasinato, Angela; Venturelli, Leonello; Privitera, Francesco; Miraglia Del Giudice, Emanuele; Sollai, Sara; Picca, Marina; Di Mauro, Giuseppe; Bruni, Oliviero; Chiappini, Elena; Bernasconi, Sergio; Bona, Gianni; Iughetti, Lorenzo; Maffeis, Claudio; Manzoni, Paola
abstract

Background: Sleep in childhood and adolescence is crucial for mental and physical health; however several researches reported an increasing trend towards a sleep deprivation in this age. Due to the lack of recent epidemiological studies in Italy, the aim of our study was to depict sleep habits and patterns in Italian children aged 1-14 years and to evaluate their relationships with video devices use (TV, tablet, smartphone, PC) and evening/night child activities. Methods: A structured interview was conducted during 2015 by 72 Family Pediatricians in 2030 healthy children aged 1-14 years by a cross-sectional survey named "Ci piace sognare". Total sleep duration was calculated, 2015 National Sleep Foundation Recommendations were used as reference. Optimal sleepers were defined children sleeping in own bed all night without awakenings. Multivariable median regression was performed to identify predictors of sleep duration and multivariable logistic regression for predictors of optimal sleep. Results: Total sleep duration and numbers of awakenings decreased with age. Only 66.9% of children had sleep duration in agreement with Recommendations (50% in 10-14 years group). Before sleeping 63.5% of children used video devices (39.6% at 1-3 years), 39.1% read, 27.5% drank and 19.5% ate. Bottle users at bedtime were 30.8% at 1-3 years, 16.6% at 3-5 years and 4.9% at 5-7 years. Overall, 23.4% of children changed sleeping place during the night, 22.4% referred sleeping problems in the first year of life. Video devices use was negative predictor of sleep duration (-0.25 h [95%CI:-0.35,-0.14], p < 0.001). Optimal sleep was inversely related with bedroom TV (OR 0.63 [0.50,0.79], p < 0.001), with sleeping disorders in the first year (OR 0.62 [0.48,0.80], p < 0.001)), with bottle use (OR 0.64 [0.44,0.94], p < 0.05) and posivively related with high mother's education level (OR 1.44 [1.11,1.88], p < 0.01). Conclusions: About one third of 1 to 14 year Italian children sleep less than recommended, one half in teenage. Modifiable risk factors for sleep abnormalities such as video devices use, bedroom TV and bottle use should be target of preventive strategies for a correct sleep. Pediatricians should give priority to the identification of sleep disorders early in life.


2017 - Spectrum of mutations in Italian patients with familial hypercholesterolemia: New results from the LIPIGEN study [Articolo su rivista]
Pirillo, Angela; Garlaschelli, Katia; Arca, Marcello; Averna, Maurizio; Bertolini, Stefano; Calandra, Sebastiano; Tarugi, Patrizia; Catapano, Alberico L.; Arca, Marcello; Averna, Maurizio; Bertolini, Stefano; Calandra, Sebastiano; Catapano, Alberico Luigi; Tarugi, Patrizia; Pellegatta, Fabio; Angelico, Francesco; Arca, Marcello; Averna, Maurizio; Bartuli, Andrea; Biasucci, Giacomo; Biolo, Gianni; Bonanni, Luca; Bonomo, Katia; Borghi, Claudio; Bossi, Antonio Carlo; Branchi, Adriana; Carubbi, Francesca; Cipollone, Francesco; Citroni, Nadia; Federici, Massimo; Ferri, Claudio; Fiorenza, Anna Maria; Giaccari, Andrea; Giorgino, Francesco; Guardamagna, Ornella; Iannuzzi, Arcangelo; Iughetti, Lorenzo; Lupattelli, Graziana; Mandraffino, Giuseppe; Marcucci, Rossella; Mombelli, Giuliana; Muntoni, Sandro; Pecchioli, Valerio; Pederiva, Cristina; Pipolo, Antonio; Pisciotta, Livia; Pujia, Arturo; Purrello, Francesco; Repetti, Elena; Rubba, Paolo; SabbÃ&nbsp;, Carlo; Sampietro, Tiziana; Sarzani, Riccardo; Tagliabue, Milena Paola; Trenti, Chiara; Vigna, Giovanni Battista; Werba, Josà Pablo; Zambon, Sabina; Zenti, Maria Grazia; Montali, Anna; Noto, Davide; Bertolini, Stefano; Calandra, Sebastiano; Fortunato, Giuliana; Grigore, Liliana; Del Ben, Maria; Maranghi, Marianna; Cefalù, A. Baldassarre; Buonuomo, Paola Sabrina; Capra, Maria Elena; Vinci, Pierandrea; D'Addato, Sergio; Galbiati, Stella; Nascimbeni, Fabio; Bucci, Marco; Spagnoli, Walter; Cardolini, Iris; Cervelli, Nazzareno; Emanuela, Colombo; Sun, Vinsin A.; Laviola, Luigi; Bello, Francesca; Chiariello, Giuseppe; Predieri, Barbara; Siepi, Donatella; Saitta, Antonino; Giusti, Betti; Pavanello, Chiara; Lussu, Milena; Prati, Lucia; Banderali, Giuseppe; Balleari, Giulia; Montalcini, Tiziana; Scicali, Roberto; Gentile, Luigi; Gentile, Marco; Suppressa, Patrizia; Sbrana, Francesco; Cocci, Guido; Benso, Andrea; Negri, Emanuele Alberto; Ghirardello, Omar; Lorenzo, Vigo; Zambon, Alberto; Enzo, Bonora; Minicocci, Ilenia; Spina, Rossella; Orlando, Camilla; Tarugi, Patrizia; Di Taranto, Maria Donata; Catapano, Alberico Luigi; Casula, Manuela; Chiodo, Lorenzo; Garlaschelli, Katia; Manzato, Enzo; Tragni, Elena
abstract

Background Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by elevated plasma levels of LDL-cholesterol that confers an increased risk of premature atherosclerotic cardiovascular disease. Early identification and treatment of FH patients can improve prognosis and reduce the burden of cardiovascular mortality. Aim of this study was to perform the mutational analysis of FH patients identified through a collaboration of 20 Lipid Clinics in Italy (LIPIGEN Study). Methods We recruited 1592 individuals with a clinical diagnosis of definite or probable FH according to the Dutch Lipid Clinic Network criteria. We performed a parallel sequencing of the major candidate genes for monogenic hypercholesterolemia (LDLR, APOB, PCSK9, APOE, LDLRAP1, STAP1). Results A total of 213 variants were detected in 1076 subjects. About 90% of them had a pathogenic or likely pathogenic variants. More than 94% of patients carried pathogenic variants in LDLR gene, 27 of which were novel. Pathogenic variants in APOB and PCSK9 were exceedingly rare. We found 4 true homozygotes and 5 putative compound heterozygotes for pathogenic variants in LDLR gene, as well as 5 double heterozygotes for LDLR/APOB pathogenic variants. Two patients were homozygous for pathogenic variants in LDLRAP1 gene resulting in autosomal recessive hypercholesterolemia. One patient was found to be heterozygous for the ApoE variant p.(Leu167del), known to confer an FH phenotype. Conclusions This study shows the molecular characteristics of the FH patients identified in Italy over the last two years. Full phenotypic characterization of these patients and cascade screening of family members is now in progress.


2017 - The Interplay among BMI z-Score, Peer Victmization, and Self-Concept in Outpatient Children and Adolescents with Overweight or Obesity [Articolo su rivista]
Bacchini, Dario; Licenziati, Maria Rosaria; Affuso, Gaetana; Garrasi, Alessandra; Corciulo, Nicola; Driul, Daniela; Tanas, Rita; Fiumani, Perla Maria; Di Pietro, Elena; Pesce, Sabino; Crinò, Antonino; Maltoni, Giulio; Iughetti, Lorenzo; Sartorio, Alessandro; Deiana, Manuela; Lombardi, Francesca; Valerio, Giuliana
abstract

Research has provided evidence that obesity is associated with peer victimization and low levels of self-concept. No study has examined the relationship between BMI z-score, self-concept in multiple domains, and peer victimization.


2017 - The rehabilitation of children and adolescents with severe or medically complicated obesity: an ISPED expert opinion document [Articolo su rivista]
Grugni, G.; Licenziati, M. R.; Valerio, G.; Crino, A.; Maffeis, C.; Tanas, R.; Morino, G. S.; Ambruzzi, A.; Balsamo, A.; Bellone, S.; Bernasconi, S.; Bianchi, V.; Bobbio, A.; Bruzzi, P.; Buongiovanni, C.; Calcagno, A.; Calcaterra, V.; Canali, T.; Cerutti, F.; Corciulo, N.; Cotugno, F.; Cuccarolo, G.; D'Amico, O.; Di Bonito, P.; Di Candia, S.; Di Pietrantonio, V.; Di Pietro, M.; Filannino, G.; Fintini, D.; Forziato, C.; Franceschi, R.; Franzese, A.; Galeazzi, D.; Gargantini, L.; Franca Giusti, L.; Gualtieri, A.; Iafusco, D.; Laura Iezzi, M.; Iughetti, L.; Lera, R.; Limauro, R.; Lombardi, F.; Lucchesi, S.; Macchiaroli, A.; Maltoni, G.; Manco, M.; Del Giudice Emanuele, M.; Modestini, E.; Morandi, A.; Mozzillo, E.; Nanni, L.; Nicolosi, A.; Pellegrin, M. C.; Peruzzi, S.; Peverelli, P.; Purromuto, S.; Ragusa, L.; Rosato, T.; Salvo, C.; Sartori, C.; Sticco, M.; Elisabeth Street, M.; Trifiro, G.; Vianelli, P.; Yiannakou, P.
abstract

Severe/medically complicated obesity in childhood, and particularly in adolescence, is a real disability that requires an intensive and continuous approach which should follow the procedures and schedule of rehabilitation medicine. Given the lack of a specific document focusing on children and adolescents, the Childhood Obesity Study Group set out to explore the available evidence for the treatment of severe or medically complicated obesity and to set standards tailored to the specific context of the Italian Health Service. Through a series of meetings and electronic communications, the writing committee (selected from members of the Study Group) selected the key issues, explored the literature and produced a draft document which was submitted to the other experts until the final synthesis was approved by the group. In brief, the following issues were involved: (1) definition and epidemiology; (2) identification of common goals designed to regain functional competence and limit the progression of metabolic and psychological complications; (3) a multi-professional team approach; (4) the care setting. This paper is an expert opinion document on the rehabilitation of severe and medically complicated obesity in children and adolescents produced by experts belonging to the Childhood Obesity Study Group of the Italian Society for Pediatric Endocrinology and Diabetology (ISPED).


2017 - Timely diagnosis of sitosterolemia by next generation sequencing in two children with severe hypercholesterolemia [Articolo su rivista]
Buonuomo, Paola Sabrina; Iughetti, Lorenzo; Pisciotta, Livia; Rabacchi, Claudio; Papadia, Francesco; Bruzzi, Patrizia; Tummolo, Albina; Bartuli, Andrea; Cortese, Claudio; Bertolini, Stefano; Calandra, Sebastiano
abstract

Severe hypercholesterolemia associated or not with xanthomas in a child may suggest the diagnosis of homozygous autosomal dominant hypercholesterolemia (ADH), autosomal recessive hypercholesterolemia (ARH) or sitosterolemia, depending on the transmission of hypercholesterolemia in the patient's family. Sitosterolemia is a recessive disorder characterized by high plasma levels of cholesterol and plant sterols due to mutations in the ABCG5 or the ABCG8 gene, leading to a loss of function of the ATP-binding cassette (ABC) heterodimer transporter G5-G8.


2017 - Una brutta caduta… [Articolo su rivista]
Norato, Alessia; Cavalleri, Elisa; Tanghetti, Paola; Spezia, Elisabetta; Sordelli, Silvia; Buzi, Fabio; Iughetti, Lorenzo
abstract


2017 - Universal Screening Program in Pregnant Women and Newborns at-Risk for Sickle Cell Disease: First Report from Northern Italy [Articolo su rivista]
Lodi, Mariachiara; Bigi, Elena; Palazzi, Giovanni; Vecchi, Lara; Morandi, Riccardo; Setti, Monica; Borsari, Silvana; Bergonzini, Giuliano; Iughetti, Lorenzo; Venturelli, Donatella
abstract

The implementation of screening programs for early detection of patients with sickle cell disease has become necessary in Italy as a result of the high rate of migration from areas with a high prevalence of the disease (Sub-Saharan Africa, Middle East and the Balkans). Following a pilot study performed in the province of Modena, Italy in 2011–2013, an official screening program was established on May 31 2014 for all pregnant women, free-of-charge for the family according to the National Guidelines for Physiological Pregnancy. Hemoglobin (Hb) profiles of pregnant women within 10 weeks of pregnancy, of new mothers at delivery and of the newborns of mothers with variant Hb profiles (newborns at-risk), were evaluated by high performance liquid chromatography (HPLC). Samples from 17,077 new mothers were analyzed and 993 showed alteration of Hb patterns (5.8%) (1.0% Hb AS carriers); of the 1011 at-risk newborns, four (0.4%) carried sickle cell disease and 90 (8.9%) were Hb AS carriers. These data show that early diagnosis of sickle cell disease or carrier status can be obtained in high-risk newborns, providing valuable information on the frequency of these conditions in geographic areas in which the disease is historically rare.


2017 - VALUTAZIONE AUXO-ENDOCRINOLOGICA DEI PAZIENTI AFFETTI DA SICKLE CELL DISEASE (SCD): DATI PRELIMINARI [Abstract in Atti di Convegno]
Mandese, Valentina; Elena, Bigi; Bruzzi, Patrizia; Predieri, Barbara; Giovanni, Palazzi; Maria Chiara Lodi, ; Bonvicini, Federico; Venturelli, Donatella; Iughetti, Lorenzo
abstract

OBIETTIVI È noto che pazienti con sickle cell disease (SCD) possono presentare problematiche auxo-endocrinologiche. Obiettivo di questo studio è quello di descrivere il pattern accrescitivo e valutare la presenza di eventuali alterazioni endocrinologiche nei pazienti con SCD seguiti nel nostro Centro. METODI Sono stati oggetto dello studio pazienti con SCD di età compresa tra 3-18 anni ed un gruppo di controllo costituito dai fratelli sani. I dati auxologici sono stati raccolti per entrambi i gruppi. Nei pazienti affetti da SCD sono stati valutati: esame emocromocitometrico, LDH, assetto lipidico e glucidico, TSH, fT4, LH, FSH, estradiolo/testosterone, prolattina, IGF1, IGFBP3, vitamina D. RISULTATI Sono stati analizzati 40 pazienti affetti da SCD (31 con genotipo HbSS, 9 HbSC, 17 femmine, età media 9,40±4,10 anni) e 14 controlli (4 femmine, età media 9,45±2,81 anni). I pazienti con SCD hanno presentato valori di SDS-altezza (-0,20±1,00 vs.1,00±0,92, p<0,01), SDS-altezza corretta per target genetico (0,30±0,80 vs. 1,55±0,76, p<0,01) e SDS-BMI (-0,30±1,40 vs. 0,91±1,28, p=0,01) inferiori rispetto al gruppo dei controlli. Il confronto tra pazienti HbSS ed HbSC non ha evidenziato differenze auxologiche. Oltre ad un’ipovitaminosi D (presente nel 75% dei casi), nel 32,5% dei pazienti è stata documentata almeno un’endocrinopatia: 5% GHD, 5% ipotiroidismo subclinico, 2,5% insuffi cienza ovarica, 2,5% ipogonadismo ipogonadotropo, 2,5% pubertà precoce, 15% insulino-resistenza. I valori medi dei parametri dell’assetto lipidico sono risultati nei limiti di norma senza differenze tra HbSS ed HbSC. I livelli di IGF-1 sono stati riscontrati maggiori nel gruppo HbSC (caratterizzato da una minore severità di malattia) rispetto HbSS (306±87,50 vs. 208±96,8 ng/ml, p=0,01). Nella popolazione totale, i valori di IGF-1 sono risultati correlati direttamente con i valori di Hb (r2 0,58, p<0,05) ed inversamente con i valori di LDH (r2 -0,50, p<0,05). CONCLUSIONI I nostri dati confermano che la SCD impatta negativamente sull’accrescimento staturo-ponderale ed evidenziano una correlazione dei livelli di IGF-1 con alcuni parametri di severità di patologia. Dal nostro studio emerge, inoltre, che oltre il 30% dei pazienti presenta già un’importante problematica di tipo endocrinologico. Questi dati, seppur preliminari, sottolineano la necessità di un regolare follow-up in una popolazione che, anche nella nostra nazione, diventa sempre più numerosa.


2017 - Valutazione auxologica e della motilità spontanea attraverso il metodo dei General Movements nel neonato a termine Small for Gestational Age [Abstract in Atti di Convegno]
Lucaccioni, Laura; Ferrari, Fabrizio; Badiali, Licia; Cingolani, Greta M.; Iughetti, Lorenzo
abstract

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2016 - A Multicenter Retrospective Survey regarding Diabetic Ketoacidosis Management in Italian Children with Type 1 Diabetes [Articolo su rivista]
Zucchini, Stefano; Scaramuzza, Andrea E; Bonfanti, Riccardo; Buono, Pietro; Cardella, Francesca; Cauvin, Vittoria; Cherubini, Valentino; Chiari, Giovanni; D'Annunzio, Giuseppe; Frongia, Anna Paola; Iafusco, Dario; Maltoni, Giulio; Patera, Ippolita Patrizia; Toni, Sonia; Tumini, Stefano; Rabbone, Ivana; Lera, R.; Bobbio, A.; Gualtieri, A.; Piccinno, E.; Zecchino, C.; Pasquino, B.; Felappi, B.; Prandi, E.; Gallo, F.; Morganti, G.; Ripoli, C.; Cardinale, G.; Ponzi, G.; Castaldo, V.; Stamati, F.; Lo Presti, D.; Tomaselli, L.; Citriniti, F.; Suprani, T.; Bensa, M.; Graziani, V.; De Berardinis, F.; Chiarelli, F.; De Marco, R.; Lazzaro, N.; De Donno, V.; Banin, P.; Piccini, B.; Lenzi, L.; Mainetti, B.; Coccioli, M. S.; Minuto, N.; Lorini, R.; Trada, M.; Sogno Valin, P.; Beccaria, L.; Lucchesi, S.; Bruzzese, M.; Mammì, F.; Cirillo, D.; Pardi, D.; Taccardi, R. A.; Lombardo, F.; Zuccotti, G. V.; Meschi, F.; Iughetti, Lorenzo; Predieri, Barbara; Franzese, A.; Mozzillo, E.; Prisco, F.; Cadario, F.; Savastio, S.; Piredda, G.; Monciotti, C.; Galderisi, A.; Salvo, C.; Calcaterra, V.; Berioli, M. G.; Federico, G.; Favia, A.; Zanette, G.; Marsciani, A.; Schiaffini, R.; Cappa, M.; Delvecchio, M.; Gaiero, A.; Ignaccolo, G.; Cerutti, F.; Fontana, F.; Guerraggio, L.; Zonca, S.; Franceschi, R.; Tornese, G.; Biagioni, M.; Salvatoni, A.; Cardani, R.; Marigliano, M.; Sabbion, A.; Maffeis, C.; Schieven, E.; Arnaldi, C.
abstract

We conducted a retrospective survey in pediatric centers belonging to the Italian Society for Pediatric Diabetology and Endocrinology. The following data were collected for all new-onset diabetes patients aged 0-18 years: DKA (pH < 7.30), severe DKA (pH < 7.1), DKA in preschool children, DKA treatment according to ISPAD protocol, type of rehydrating solution used, bicarbonates use, and amount of insulin infused. Records (n = 2453) of children with newly diagnosed diabetes were collected from 68/77 centers (87%), 39 of which are tertiary referral centers, the majority of whom (n = 1536, 89.4%) were diagnosed in the tertiary referral centers. DKA was observed in 38.5% and severe DKA in 10.3%. Considering preschool children, DKA was observed in 72%, and severe DKA in 16.7%. Cerebral edema following DKA treatment was observed in 5 (0.5%). DKA treatment according to ISPAD guidelines was adopted in 68% of the centers. In the first 2 hours, rehydration was started with normal saline in all centers, but with different amount. Bicarbonate was quite never been used. Insulin was infused starting from third hour at the rate of 0.05-0.1 U/kg/h in 72% of centers. Despite prevention campaign, DKA is still observed in Italian children at onset, with significant variability in DKA treatment, underlying the need to share guidelines among centers.


2016 - Body emotional map: an innovative and useful tool to improve parents´ adaptation to the diagnosis of type 1 diabetes of their child [Abstract in Rivista]
Predieri, Barbara; Nicolucci, Antonio; Alessandrelli, Maria Cristina; Pagnini, Manuela; Pintaudi, B.; Zani, Fabiana; Iannilli, Antonio; Ferrito, Lucia; Lucisano, G.; Iughetti, Lorenzo; Cherubini, Valentino
abstract

Objectives: The diagnosis of type 1 diabetes mellitus (T1DM) in a child is a traumatic event for parents. The path of a good adaptation to the child´s disease is a purpose of the therapeutic education to attain and keep a good quality of life. Aim of this study was to demonstrate the effectiveness of the new tool Body Emotional Map (BEM) in helping parents to overcome the trauma of T1DM diagnosis and to achieve the best adaptation. Methods: Sixty-two parents (29 mothers, 33 fathers) of 36 children with T1DM (age = 11.3 3.3 yrs; T1DM duration >1 yr; HbA1c = 57 11 mmol/mol) were recruited in a 3-days educational group intervention study. The re-examine of the traumatic event of the T1DM diagnosis through the BEM path included spatial and time-line anchorage, retrace of the future, emotional awareness, interactive discussion. Relaxing technique, diaphragmatic breathing, and guided visualization were used by 1 psychologist, 1 counselor and 1 pediatric diabetologist. Self-report questionnaires [Diabetes Related Distress (DRD), Parent Stress Index Short Form scale (PSI-SF), Fear of Hypoglycemia Survey (FHS), Parent Health Locus of Control Scale (PHLOC), and Health Survey Short Form-36 (SF-36)] were filled by parents at baseline, 1 month (M1), and 3 months (M3) after the intervention. Results: Respect to baseline, at time M3 we found a significant score reduction of the “difficult child” subscale of the PSI-SF in both parents (p < 0.05), of the DRD in mothers (59.0 2.6 vs. 52.4 2.7, p = 0.03), and of the “parental distress” subscale of the PSI-SF in fathers (24.9 1.5 vs. 21.8 1.5, p = 0.04) . Moreover, the social functioning score of the SF-36 was significantly improved in fathers at time M1 (81.3 3.2 vs. 88.3 3.2, p = 0.03). Conclusions: In T1DM we must always to consider the emotional reaction occurring when the diagnosis is given both in children and parents. BEM path seems to reduce stress and to improve social functioning of parents of children and adolescents with T1DM.


2016 - Cell therapies for pancreatic beta-cell replenishment. [Articolo su rivista]
Okere, Bernard; Lucaccioni, Laura; Dominici, Massimo; Iughetti, Lorenzo
abstract

The current treatment approach for type 1 diabetes is based on daily insulin injections, combined with blood glucose monitoring. However, administration of exogenous insulin fails to mimic the physiological activity of the islet, therefore diabetes often progresses with the development of serious complications such as kidney failure, retinopathy and vascular disease. Whole pancreas transplantation is associated with risks of major invasive surgery along with side effects of immunosuppressive therapy to avoid organ rejection. Replacement of pancreatic beta-cells would represent an ideal treatment that could overcome the above mentioned therapeutic hurdles. In this context, transplantation of islets of Langerhans is considered a less invasive procedure although long-term outcomes showed that only 10 % of the patients remained insulin independent five years after the transplant. Moreover, due to shortage of organs and the inability of islet to be expanded ex vivo, this therapy can be offered to a very limited number of patients. Over the past decade, cellular therapies have emerged as the new frontier of treatment of several diseases. Furthermore the advent of stem cells as renewable source of cell-substitutes to replenish the beta cell population, has blurred the hype on islet transplantation. Breakthrough cellular approaches aim to generate stem-cell-derived insulin producing cells, which could make diabetes cellular therapy available to millions. However, to date, stem cell therapy for diabetes is still in its early experimental stages. This review describes the most reliable sources of stem cells that have been developed to produce insulin and their most relevant experimental applications for the cure of diabetes.


2016 - Diagnosis of metabolic disease by imaging techniques [Abstract in Rivista]
Iughetti, Lorenzo
abstract

An increasing number of studies focus on fat distribution and its associations with metabolic risk, in interaction with genetics, environment and ethnicity, in children. The link between obesity and metabolic disease risk is driven by body fat distribution and ectopic fat deposition, but the only way to accurately visualize and quantify specific fat depots is state-of-the-art imaging techniques like computed tomography (CT) and magnetic resonance imaging (MRI). Recent advances in imaging techniques, especially in MRI, have made it possible to measure specific fat depots such as visceral abdominal fat (visceral adipose tissue [VAT]), subcutaneous abdominal fat (subcutaneous adipose tissue [SAT]) and ectopic fat depots including hepatic fat fraction (HFF), pancreatic fat fraction (PFF) and intramyocellular fat (IMCL fat. Abdominal as well as ectopic fat depots are present already in childhood and contribute to abnormal metabolic parameters, starting early in life. Visceral, hepatic and intramuscular fat seem to be interrelated but their patterns as well as their independent contribution on metabolic risk are not clear. Girls tend to accumulate more TBF and SAT during and after puberty, depositing fat preferentially in the gynoid and extremity regions. In contrast, pubertal and postpubertal boys tend to deposit more fat in the abdominal region, particularly in the VAT depot. Sexual maturation significantly influences TBF, VAT and SAT. Some ethnic-specific characteristics are also prevalent. Further research are needed in childhood obesity by using imaging techniques such as magnetic resonance imaging and computed tomography. These imaging methods can provide a better understanding of fat distribution and its relationships with metabolic risk, compared to less detailed fat and obesity assessment. However, studies on bigger samples and with a prospective character are warranted.


2016 - Drepanocitosi. Nuovi aspetti della diagnosi precoce e della cura  [Articolo su rivista]
Bigi, Elena; Palazzi, Giovanni; Lucaccioni, Laura; Iughetti, Lorenzo
abstract

: La drepanocitosi (SCD) è uno dei più diffusi disordini monogenici al mondo. E’ caratterizzata da ricorrenti crisi dolorose vaso-occlusive (VOC) e complicanze respiratorie (ACS), cause principali di accesso ai Dipartimenti di Emergenza.


2016 - Duplications upstream and downstream of SHOX identified as novel causes of Leri-Weill dyschondrosteosis or idiopathic short stature. [Articolo su rivista]
Bunyan, Dj; Baffico, M; Capone, L; Vannelli, S; Iughetti, Lorenzo; Schmitt, S; Taylor, Ej; Herridge, Aa; Shears, D; Forabosco, A; Coviello, D. a.
abstract

Leri-Weill dyschondrosteosis is a pseudoautosomal dominantly-inherited skeletal dysplasia ascribed to haploinsufficiency of the SHOX gene caused by deletions, point mutations, or partial duplications of the gene, or to heterozygous deletions upstream or downstream of the intact SHOX gene involving conserved non-coding cis-regulatory DNA elements that show enhancer activity. Recently, two SHOX conserved non-coding element duplications, one upstream and one downstream, were reported in patients referred with idiopathic short stature. To further evaluate the role of these duplications in SHOX-related disorders, we describe seven patients (five with Leri-Weill dyschondrosteosis and two with short stature) all of whom have duplications of part of the upstream or downstream conserved non-coding element regions, identified by multiplex ligation-dependent probe amplification. In addition, we show data from 32 patients with an apparently identical downstream duplication that includes a proposed putative regulatory element (identified by multiplex ligation-dependent probe amplification or array comparative genome hybridization), which results in a variable phenotype from normal to mild Leri-Weill dyschondrosteosis. These additional data provide further evidence that duplications of upstream and downstream long range cis-regulatory DNA elements can result in a SHOX-related phenotype.


2016 - Effects of nutritional intake on disease severity in children with sickle cell disease. [Articolo su rivista]
Mandese, Valentina; Marotti, Francesca; Bedetti, Luca; Bigi, E; Palazzi, G; Iughetti, Lorenzo
abstract

BACKGROUND: Children with Sickle Cell Disease (SCD) may show growth failure in comparison to healthy peers. Many factors as hematological status, endocrine and/or metabolic dysfunction, and nutritional status, may play an important role in growth failure. The aim of this study was to assess whether impaired growth and nutritional intake can affect SCD severity during childhood. METHODS: We conducted an observational study on children with SCD referring to our clinic for routine follow-up visits in a 6-month period. We collected information on weight, height and body mass index (BMI) and calculated their respective standardized scores (z). The nutritional intake was assessed through the last 24-h recall intake of total calories, macro- (proteins, lipids, carbohydrates) and micronutrients (calcium, iron, phosphorus, vitamins B1, PP, A, C, B2). Disease severity was assessed through total hemoglobin (Hb) and fetal hemoglobin (HbF), and lactic dehydrogenase (LDH) levels, and through the total number and days of hospitalizations, as well as the lifetime episodes of acute chest syndrome (ACS). RESULTS: Twenty nine children (14 males, 15 females) with SCD were enrolled; their mean age was 9.95 years (SD 3.50, min 3.72, max 17.18). Z-weight and z-BMI were significantly directly related to total Hb. Food intake resulted significantly unbalanced in terms of total calorie intake, macro- and micronutrients, especially calcium, iron, vitamin B1 and C. Low intake of calcium and vitamin B1 were significantly inversely correlated with number and days of hospitalizations per year. Protein, lipid, phosphorus, and vitamin PP intakes resulted adequate but were inversely correlated with number and days of hospitalizations. Carbohydrate, lipid, iron, phosphorus, vitamins B1 and B2 intakes were significantly inversely correlated to HbF levels. CONCLUSIONS: This study showed that, in our population, inadequate nutritional intake, weight and BMI have a significant impact on SCD severity indices.


2016 - Efficacy and safety of growth hormone treatment in children with short stature: the Italian cohort of the GeNeSIS clinical study [Articolo su rivista]
Cappa, M.; Iughetti, L.; Loche, S.; Maghnie, M.; Vottero, A; GeNeSIS National Board on behalf of the GeNeSIS Italian Investigators, ; Franco, Antoniazzi; Luciano, Beccaria; Sergio, Bernasconi; Domenico, Caggiano; Manuela, Caruso-Nicoletti; Alessandra, Catucci; Francesco, Chiarelli; Stefano, Cianfarani; Annarita, Colucci; Francesca De Rienzo, ; Raffaele Di Pumpo, ; Alessandra Di Stasio, ; Giovanni, Farello; Leonardo, Felici; Pasquale, Femiano; Luigi, Garagantini; Claudia, Giavoli; Nellaaugusta, Greggio; Laura, Guazzarotti; Daniela, Larizza; Mariarosaria, Licenziati; Antonella, Lonero; Mariacristina, Maggio; Alberto, Marsciani; Patrizia, Matarazzo; Laura, Mazzanti; Beatrice, Messini; Flavia, Napoli; Annamaria, Pasquino; Laura, Perrone; Sabrina, Pilia; Alba, Pilotta; Marzia, Piran; Gabriella, Pozzobon; Predieri, Barbara; Michele, Sacco; Mariacarolina, Salerno; Antonina, Tirendi; Graziamaria, Ubertini; Silvia, Vannelli; Malgorzata, Wasniewska; Maria, Zampolli; Martina, Zanotti; Gianvincenzo, Zuccotti
abstract

Purpose: We examined auxological changes in growth hormone (GH)-treated children in Italy using data from the Italian cohort of the multinational observational Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS) of pediatric patients requiring GH treatment. Methods: We studied 711 children (median baseline age 9.6&nbsp;years). Diagnosis associated with short stature was as determined by the investigator. Height standard deviation score (SDS) was evaluated yearly until final or near-final height (n&nbsp;=&nbsp;78). Adverse events were assessed in all GH-treated patients. Results: The diagnosis resulting in GH treatment was GH deficiency (GHD) in 85.5&nbsp;% of patients, followed by Turner syndrome (TS 6.6&nbsp;%). Median starting GH dose was higher in patients with TS (0.30&nbsp;mg/kg/week) than patients with GHD (0.23&nbsp;mg/kg/week). Median (interquartile range) GH treatment duration was 2.6 (0.6–3.7) years. Mean (95&nbsp;% confidence interval) final height SDS gain was 2.00 (1.27–2.73) for patients with organic GHD (n&nbsp;=&nbsp;18) and 1.19 (0.97–1.40) for patients with idiopathic GHD (n&nbsp;=&nbsp;41), but lower for patients with TS, 0.37 (−0.03 to 0.77, n&nbsp;=&nbsp;13). Final height SDS was&nbsp;&gt;−2 for 94&nbsp;% of organic GHD, 88&nbsp;% of idiopathic GHD and 62&nbsp;% of TS patients. Mean age at GH start was lower for organic GHD patients, and treatment duration was longer than for other groups, resulting in greater mean final height gain. GH-related adverse events occurred mainly in patients diagnosed with idiopathic GHD. Conclusions: Data from the Italian cohort of GeNeSIS showed auxological changes and safety of GH therapy consistent with results from international surveillance databases.


2016 - Efficacy and safety of insulin degludec in children and adolescents with type 1 diabetes [Abstract in Rivista]
Predieri, Barbara; Bruzzi, Patrizia; Maltoni, Giulio; Zucchini, Stefano; Iughetti, Lorenzo
abstract

Objectives: Degludec (IDeg; Tresiba®) is a novel basal insulin with an ultra-long, flat and stable action profile. In adults, it was demonstrated to provide more glucose-lowering effects and lower rates of hypoglycemia respect to glargine (IGlar). To date studies on childhoods´ IDeg use are scarce. Aim of this study was to assess the efficacy and the safety of IDeg in children and adolescents with type 1 diabetes (T1DM) previously treated with IGlar. Methods: Twenty children and adolescents with T1DM (15.1 4.0 yrs; 9 males; 7 prepubertal; T1DM duration 7.2 3.7 yrs; IGlar treatment at least 1 year) were recruited in the study and shifted to IDeg once daily. Anthropometric (BMI-SDS), metabolic [HbA1c, FPG, and severe hypoglycaemia rates], and insulin dose [IGlar or IDeg plus short-acting or regular] were collected at baseline (T0, during IGlar treatment), 3 months (T1), and 6 months (T2) after IDeg was started. Data were analysed according to pubertal status. Results: BMI-SDS did not change on IDeg both in prepubertal and in pubertal patients. Despite HbA1c values were not significantly improved during IDeg treatment (ΔHbA1c T0-T1 -0.3%, p = 0.1; T0-T2 -0.1%, p = 0.6), FPG was significantly decreased at T1 (−18.6 34.1 mg/dl, p = 0.05). No episode of severe hypoglycaemia was reported on IDeg. We found a significant reduction in doses of both basal insulin (IGlar vs. IDeg: 21.8 8.9 vs. 19.4 7.8 IU/day, p = 0.003) and short-acting or regular mealtime insulin (T0 vs. T2 0.56 0.13 vs. 0.50 0.15 IU/kg/day, p = 0.02). Conclusions: In our patients, IDeg seems effective to improve the glycemic control reducing FPG even at lower basal insulin doses compared to IGlar. Moreover, it allowed the reduction of the dose of mealtime insulin. No episode of acute complication was reported suggesting how IDeg may be consider safe also in childhood.


2016 - Erratum: Organization and regional distribution of centers for the management of children and adolescents with diabetes in Italy (Ital J Pediatr (2015) 41 (74) DOI:10.1186/s13052-015-0179-6) [Articolo su rivista]
Giorgetti, C.; Ferrito, L.; Zallocco, F.; Iannilli, A.; Cherubini, V.; Maghnie, M.; Rabbone, I.; Lera, R.; De Luna, L.; Kienberger, B.; Gualtieri, A.; Zecchino, C.; Piccino, E.; Ortolani, F.; Zucchini, S.; Maltoni, G.; Pasquino, B.; Reinstadler, P.; Prandi, E.; Zattoni, V.; Gallo, F.; Morganti, G.; Guerraggio, L.; Ripoli, C.; Frongia, M.; Pusceddu, P.; La Loggia, A.; Scanu, P.; Cardinale, G.; Ponzi, G.; Tomaselli, L. G.; Rapisarda, V.; Citriniti, F.; Soprani, T.; Tumini, S.; Lazzaro, N.; De Donno, V.; Banin, P.; Toni, S.; Lenzi, L.; Mainetti, B.; Coccioli, M. S.; D'Annunzio, G.; Minuto, N.; Montani, E.; Maccioni, R.; Marongiu, U.; Beccaria, L.; Bruzzese, M.; Mammi, F.; Pardi, D.; Lombardo, F.; Ventrici, C.; Scaramazza, A.; Ferrari, M.; Bonfanti, R.; Rigamonti, A.; Iughetti, L.; Predieri, B.; Iafusco, D.; Confetto, S.; Zanfardino, A.; Prisco, F.; Francese, A.; De Nitto, E.; Cadario, F.; Milia, A.; Piredda, G.; Mereu, L.; Soro, M.; Correddu, A.; Pipia, A.; Monciotti, C.; Cardella, F.; De Berardinis, F.; Santoro, G.; Chiari, G.; Berioli, M. G.; Federico, G.; Zanette, G.; Marsciani, A.; Pedini, A.; Patera, I. P.; Schiaffini, R.; Bitti, M.; Lidano, R.; Pietrosanti, S.; Delvecchio, M.; Trada, M.; Marinaro, A.; Meloni, G.; Gaiero, A.; Fichera, G.; Bulciolu, P.; Rabbone, I.; Ignaccolo, G.; Cauvin, V.; Franceschi, R.; Faleschini, E.; Tornese, G.; Salvatoni, A.; Cardani, R.; Maffeis, C.; Marigliano, M.; Sabbion, A.; Arnaldi, C.
abstract


2016 - Gut Microbiota and Celiac Disease. [Articolo su rivista]
Marasco, G; Di Biase, Ar; Schiumerini, R; Eusebi, Lh; Iughetti, Lorenzo; Ravaioli, F; Scaioli, E; Colecchia, A; Festi, D.
abstract

Recent evidence regarding celiac disease has increasingly shown the role of innate immunity in triggering the immune response by stimulating the adaptive immune response and by mucosal damage. The interaction between the gut microbiota and the mucosal wall is mediated by the same receptors which can activate innate immunity. Thus, changes in gut microbiota may lead to activation of this inflammatory pathway. This paper is a review of the current knowledge regarding the relationship between celiac disease and gut microbiota. In fact, patients with celiac disease have a reduction in beneficial species and an increase in those potentially pathogenic as compared to healthy subjects. This dysbiosis is reduced, but might still remain, after a gluten-free diet. Thus, gut microbiota could play a significant role in the pathogenesis of celiac disease, as described by studies which link dysbiosis with the inflammatory milieu in celiac patients. The use of probiotics seems to reduce the inflammatory response and restore a normal proportion of beneficial bacteria in the gastrointestinal tract. Additional evidence is needed in order to better understand the role of gut microbiota in the pathogenesis of celiac disease, and the clinical impact and therapeutic use of probiotics in this setting.


2016 - High frequency of diabetic ketoacidosis at diagnosis of type 1 diabetes in Italian children: A nationwide longitudinal study, 2004-2013 [Articolo su rivista]
Cherubini, Valentino; Skrami, Edlira; Ferrito, Lucia; Zucchini, Stefano; Scaramuzza, Andrea; Bonfanti, Riccardo; Buono, Pietro; Cardella, Francesca; Cauvin, Vittoria; Chiari, Giovanni; D'Annunzio, Giuseppe; Frongia, Anna Paola; Iafusco, Dario; Patera, Ippolita Patrizia; Toni, Sonia; Tumini, Stefano; Rabbone, Ivana; Lombardo, Fortunato; Carle, Flavia; Gesuita, Rosaria; Lera, Riccardo; De Luna, Livia; Gualtieri, Antonella; Zecchino, Clara; Piccinno, Elvira; Reinstadler, Petra; Prandi, Elena; Gallo, Francesco; Morganti, Gianfranco; Ripoli, Carlo; La Loggia, Alfonso; Scanu, Piera; Cardinale, Giuliana; Tomaselli, Letizia Grazia; Citriniti, Felice; Lazzaro, Nicola; De Donno, Valeria; Mainetti, Benedetta; Coccioli, Maria Susanna; Maccioni, Rosella; Marongiu, Ugo; Bruzzese, Mariella; Iannilli, Antonio; Pardi, Daniela; Confetto, Santino; Zanfardino, Angela; Iughetti, Lorenzo; Franzese, Adriana; Cadario, Francesco; Milia, Anna Franca; Piredda, Gavina; Soro, Miriam; Correddu, Antonella; Galderisi, Alfonso; De Berardinis, Fiorella; Federico, Giovanni; Zanette, Giorgio; Suprani, Tosca; Pedini, Annalisa; Bitti, Maria Luisa Manca; Delvecchio, Maurizio; Trada, Michela; Meloni, Gianfranco; Gaiero, Alberto; Bulciolu, Pasquale; Guerraggio, Lucia; Faleschini, Elena; Zanatta, Manuela; Salvatoni, Alessandro; Maffeis, Claudio; Arnaldi, Claudia
abstract

This longitudinal population-based study analyses the frequency of diabetic ketoacidosis (DKA) at type 1 diabetes diagnosis in Italian children under 15 years of age, during 2004-2013. DKA was defined as absent (pH ≥ 7.30), mild/moderate (7.1 ≤ pH &lt; 7.30) and severe (pH &lt; 7.1). Two multiple logistic regression models were used to evaluate the time trend of DKA frequency considered as present versus absent and severe versus absent, adjusted for gender, age group and geographical area of residence at diagnosis. Overall, 9,040 cases were ascertained. DKA frequency was 40.3% (95%CI: 39.3-41.4%), with 29.1% and 11.2% for mild/moderate and severe DKA, respectively. Severe DKA increased significantly during the period (OR = 1.03, 95%CI: 1.003-1.05). Younger-age children and children living in Southern Italy compared to Central Italy were at significantly higher risk of DKA and severe DKA. Family history of type 1 diabetes and residence in Sardinia compared to Central Italy were significantly associated with a lower probability of DKA and severe DKA. The high frequency of ketoacidosis in Italy over time and high variability among age groups and geographical area of residence, strongly suggests a continuing need for nationwide healthcare strategies to increase awareness of early detection of diabetes.


2016 - High prevalence of hypertension in children and adolescents with type 1 diabetes identified through the 24 hours ambulatory blood pressure monitoring [Abstract in Rivista]
Iughetti, Lorenzo; Bianco, Valentina; Bonvicini, Federico; Cattelani, Chiara; Malmusi, Giovanni; Roncuzzi, Federica; Spaggiari, Valentina; Madeo, Simona Filomena; Bruzzi, Patrizia; Predieri, Barbara
abstract

Objectives: In children and adolescents with type 1 diabetes (T1DM) the usefulness of 24-hours ambulatory blood pressure monitoring (ABPM) to predict kidney diseases and cardiovascular morbidity is still controversial. Aim of this study was to identify blood pressure abnormalities using both traditional clinic and 24 h-ABPM tools and their relationship with anthropometric, kidney, and metabolic data. Methods: Forty patients (52.5% males) with T1DM (age = 13.6 2.56 yrs; T1DM duration >1 yr) were recruited in the study. Anthropometric, metabolic (HbA1c, lipid profile, renal function parameters), and blood pressure (clinic visit and 24 h-ABPM) data were collected. Hypertension was defined as: A) systolic blood pressure (SBP) above 95 centile according to age, gender, and height centile, and B) SBP above 95 centile in more than 25% of 24 h-ABPM. Results: Hypertension was found in 9 out of 40 patients (22.5%) using data by clinic visit while through 24 h-ABPM its prevalence significantly increased to 57.5% (χ2 = 8.58, p = 0.003). Subjects with hypertension, according to 24 h-ABPM, had a longer duration of T1DM than normotensive ones (8.04 3.22 vs. 5.76 1.85 yrs, respectively, p = 0.013). Six out of 40 patients did not present the phenomena of dipping (3/6 classified as hypertensive). Considering the whole population, a significant and positive correlation was demonstrated between 24 h-ABPM SBP and BMI-SDS (r = 0.38, p = 0.020) and clinic visit SBP (r = 0.42, p = 0.007). No other significant data was found. Conclusions: The 24-hours ABPM has allowed us to identify a higher prevalence of hypertension compared to that we found using SBP data from the clinic visit. Despite subjects with hypertension have had T1DM for longer time, our data did not support a relationship between SBP, metabolic control, lipid profile, and renal function. We can considered ABPM a useful tool to precociously identify these patients who may benefit from early therapeutic treatment to prevent disease progression.


2016 - Hypercholesterolemia in Childhood: How the Response to Diet could Lead to Diagnosis. Lesson from a Case-Report [Abstract in Rivista]
Bruzzi, Patrizia; Predieri, Barbara; Madeo, Simona Filomena; Rabacchi, Claudio; Tarugi, Patrizia Maria; Calandra, Sebastiano; Iughetti, Lorenzo
abstract

Sitosterolemia shares clinical and biochemical features with homozygous familial hypercholesterolemia. Nevertheless, it is impressively responsive to cholesterol-lowering diet. In our report, we demonstrate a rapid reduction of severe hypercholesterolemia in response to dietary restriction in a young patient leading to the diagnosis of this rare disease. Early identification and treatment may prevent premature atherosclerosis.


2016 - Il ruolo della Scuola di Specializzazione di Pediatria di Unimore nell’assistenza ai bambini vittime di terremoto [Capitolo/Saggio]
Iughetti, Lorenzo; Codifava, Margherita; Vellani, Giulia; Pietrangiolillo, Zaira; Cipolli, Stefania; Venturelli, Cristina; Lucaccioni, Laura.
abstract

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2016 - Impatto degli eventi tellurici del 2012 sul controllo glicemico di bambini e adolescent affetti da diabete mellito di tipo 1 [Capitolo/Saggio]
Bruzzi, Patrizia; Predieri, Barbara; Madeo Simona, F; Lucaccioni, Laura; Iughetti, Lorenzo.
abstract

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2016 - In Children with Autoimmune Thyroid Diseases the Association with Down syndrome can Modify the Clustering of Extra-Thyroidal Autoimmune Disorders [Abstract in Rivista]
Aversa, Tommaso; Valenzise, Mariella; Corrias, Andrea; Salernoc, Mariacarolina; Iughetti, Lorenzo; Tessaris, Daniele; Capalbo, Donatella; Predieri, Barbara; De Luca, Filippo; Wasniewska, Malgorzata
abstract

In a study population of children and adolescents with AITDs the association with DS might be able to: a) condition an increased risk of developing ETADs; b) modify the clustering of ETADs, which is generally observed in the children with AITDs but without DS, by favouring the aggregation of alopecia areata, vitiligo and celiac disease


2016 - In children with autoimmune thyroid diseases the association with Down syndrome can modify the clustering of extra-thyroidal autoimmune disorders [Articolo su rivista]
Aversa, Tommaso; Valenzise, Mariella; Corrias, Andrea; Salerno, Mariacarolina; Iughetti, Lorenzo; Tessaris, Daniele; Capalbo, Donatella; Predieri, Barbara; De Luca, Filippo; Wasniewska, Malgorzata
abstract

BACKGROUND: It is known that the association with Down syndrome (DS) can affect the phenotypic expression of autoimmune thyroid diseases (AITDs), whilst is unknown whether the clustering of extra-thyroidal autoimmune diseases (ETADs) may also be atypical in DS children. METHODS: The aim of this study was to investigate the clustering of ETADs in 832 children with AITDs divided in two groups with or without DS (A and B, respectively) and in four subgroups of patients aged either &lt;6 or ≥6 years. RESULTS: The rate of children with ETADs was significantly higher in Group A; in particular, alopecia areata (p=0.00001) and vitiligo (p=0.00001) were found more often in Group A irrespective of age, whilst the distribution of T1 diabetes mellitus was not different in the two groups. Celiac disease prevalence was significantly higher in DS patients only in the older subgroup. CONCLUSIONS: The association with DS may be able to modify the clustering of ETADs in the children with AITDs by favoring the aggregation of some specific diseases such as alopecia areata and vitiligo.


2016 - Issues in Diagnosis and Treatment of Type 1 Diabetes Mellitus in Childhood [Articolo su rivista]
Lucaccioni, Laura; Iughetti, Lorenzo
abstract

Type 1 Diabetes Mellitus remains one of the most complex chronic diseases in childhood. Although advances in knowledge and technology, as the use of insulin pumps or glucose sensors, have improved the quality of life of patients, the onset of the disease, as well as long-term treatment and diet, are pitfalls for families and clinicians. It is important to bear in mind that acute, life-threatening consequences of uncontrolled diabetes are hyperglycemia with ketoacidosis, both in new diagnosis and in patients already on treatment, and may be hidden by other symptoms. Moreover, treatment with insulin and diet should always be tailored on lifestyle habits and age of the patient. Aim of this work is to briefly summarise and comment what are the worst insidious aspects of Diabetes and what are the best strategies to improve the management of the disease in childhood.


2016 - Le comunicazioni orali presentate dagli specializzandi al congresso tabiano xxv [Articolo su rivista]
Cenciarelli, V.; Roncuzzi, F.; Di Biase, A. R.; Iughetti, L.
abstract


2016 - Long-term safety and efficacy of Omnitrope®, a somatropin biosimilar, in children requiring growth hormone treatment: Italian interim analysis of the PATRO Children study [Articolo su rivista]
Iughetti, Lorenzo; Tornese, Gianluca; Street, Maria Elisabeth; Napoli, Flavia; Giavoli, Claudia; Antoniazzi, Franco; Stagi, Stefano; Luongo, Caterina; Azzolini, Sara; Ragusa, Letizia; Bona, Gianni; Zecchino, Clara; Aversa, Tommaso; Persani, Luca; Guazzarotti, Laura; Zecchi, Emiliano; Pietropoli, Alberto; Zucchini, Stefano
abstract

Background: PATRO Children is an ongoing observational, longitudinal, non-interventional, global post-marketing surveillance study, which is investigating the long-term safety and effectiveness of Omnitrope®, a somatropin biosimilar to Genotropin®, in children with growth disturbances. The primary endpoint of PATRO Children is long-term safety and the secondary endpoint is effectiveness, which is assessed by analysing auxological data such as height (HSDS) and height velocity (HVSDS) standard deviation scores. Here, we report the data from the Italian interim analysis of PATRO Children data up to August 2015. Methods: PATRO Children is enrolling children who are diagnosed with conditions of short stature requiring GH treatment and are receiving Omnitrope®. Adverse events (AEs) are assessed in all Omnitrope®-treated patients. Height is evaluated yearly to near-adult (final) height, and is herein reported as HSDS; height velocity is also assessed and reported as a standard deviation score (HVSDS). Results: Up to August 2015, a total of 186 patients (mean age 10.2 years, 57.5 % males) were enrolled :156 [84 %] had growth hormone deficiency, 12 [6.5 %] were born small for gestational age, seven [3.8 %] had Prader-Willi syndrome, one [0.5 %] had Turner syndrome and one [0.5 %] had chronic renal insufficiency; seven [3.8 %] patients had other indication profiles. The mean treatment duration with Omnitrope® was 28.1 ± 19.1 months. AEs were reported in 35.6 % of patients and included headache, pyrexia, arthralgia, abdominal pain, leg and/or arm pain and increased blood creatine phosphokinase. Two serious AEs in two patients were thought to be drug-related; one patient experienced a minimal increase in a known residual craniopharyngioma, and another a gait disturbance with worsening of walking difficulties. Similar to investigational studies, Omnitrope® treatment was associated with improvements in both HSDS and HVSDS. Conclusions: Omnitrope® appears to be well tolerated and effective for the treatment of a wide range of paediatric indications, which is consistent with the outcomes from controlled clinical trials. These results need to be interpreted with caution until the data from the global PATRO Children study are available.


2016 - Natural history and life-threatening complications in Myhre syndrome and review of the literature [Articolo su rivista]
Baccilieri, Federica; Iughetti, Lorenzo
abstract

Myhre syndrome (OMIM 139210) is a rare developmental disorder inherited as an autosomal dominant trait and caused by a narrow spectrum of missense mutations in the SMAD4 gene. The condition features characteristic face, short stature, skeletal anomalies, muscle pseudohypertrophy, restricted joint mobility, stiff and thick skin, and variable intellectual disability. While most of the clinical features manifest during childhood, the diagnosis may be challenging during the first years of life. We report on the evolution of the clinical features of Myhre syndrome during childhood in a subject with molecularly confirmed diagnosis. The clinical records of 48 affected patients were retrospectively analysed to identify any early clinical signs characterizing this disorder and to better delineate its natural history. We also note that pericarditis and laryngotracheal involvement represent important life-threatening complications of Myhre syndrome that justify the recommendation for cardiological and ENT follow-up for these patients.Conclusion: Short length/stature, short palpebral fissures, and brachydactyly with hyperconvex nails represent signs/features that might lead to the correct diagnosis in the first years of life and direct to the proper molecular analysis. We underline the clinical relevance of pericarditis and laryngotracheal stenosis as life-threatening complications of this disorder and the need for careful monitoring, in relation to their severity.


2016 - Novel insights in the management of sickle cell disease in childhood. [Articolo su rivista]
Iughetti, Lorenzo; Bigi, E; Venturelli, D.
abstract

Sickle cell disease (SCD) is a life-threatening genetic disorder characterized by chronic hemolytic anemia, vascular injury and multiorgan dysfunctions. Over the last few decades, there have been significant improvements in SCD management in Western countries, especially in pediatric population. An early onset of prophylaxis with Penicillin and a proper treatment of the infections have increased the overall survival in childhood. Nevertheless, management of painful episodes and prevention of organ damage are still challenging and more efforts are needed to better understand the mechanisms behind the development of chronic organ damages. Hydroxyurea (Hydroxycarbamide, HU), the only medication approved as a disease-modifying agent by the United States Food and Drug Administration and the European Medicines Agency, is usually under-used, especially in developing countries. Currently, hematopoietic stem-cell transplantation is considered the only curative option, although its use is limited by lack of donors and transplant-related toxicity. SCD symptoms are similar in children and adults, but complications and systemic organ damages increase with age, leading to early mortality worldwide. Experts in comprehensive care of young patients with SCD, especially those approaching the transition age to adulthood, are missing, leading people to rely on urgent care, increasing health care utilization costs and inappropriate treatments. It would be important to establish programs of comprehensive healthcare for patients with SCD from birth to adulthood, to improve their quality and expectancy of life.


2016 - Occhio al Drusen.... [Articolo su rivista]
Bursi, Simona; Vivi, Giulia; Iughetti, Lorenzo
abstract

Il Drusen del disco ottico è un'anomalia congenita rara, degenerativa, lentamente progressiva, caratterizzata dalladeposizione di materiale ialino e calcifico a carico del disco ottico. Ha una prevalenza stimata dello 0.4% nei pazienti pediatrici, con una età media alla diagnosi di 12.1 anni ed è bilaterale nel 75% dei casi,


2016 - Potency biomarker signature genes from multiparametric osteogenesis assays: Will cGMP human bone marrow mesenchymal stromal cells make bone? [Articolo su rivista]
Murgia, Alba; Veronesi, Elena; Candini, Olivia; Caselli, Anna; D'Souza, Naomi; Rasini, Valeria; Giorgini, Andrea; Catani, Fabio; Iughetti, Lorenzo; Dominici, Massimo; Burns, Jorge S.
abstract

In skeletal regeneration approaches using human bone marrow derived mesenchymal stromal cells (hBM-MSC), functional evaluation before implantation has traditionally used biomarkers identified using fetal bovine serum-based osteogenic induction media and time courses of at least two weeks. However, emerging pre-clinical evidence indicates donordependent discrepancies between these ex vivo measurements and the ability to form bone, calling for improved tests. Therefore, we adopted a multiparametric approach aiming to generate an osteogenic potency assay with improved correlation. hBM-MSC populations from six donors, each expanded under clinical-grade (cGMP) conditions, showed heterogeneity for ex vivo growth response, mineralization and bone-forming ability in a murine xenograft assay. A subset of literature-based biomarker genes was reproducibly upregulated to a significant extent across all populations as cells responded to two different osteogenic induction media. These 12 biomarkers were also measurable in a one-week assay, befitting clinical cell expansion time frames and cGMP growth conditions. They were selected for further challenge using a combinatorial approach aimed at determining ex vivo and in vivo consistency. We identified five globally relevant osteogenic signature genes, notably TGF-β1 pathway interactors; ALPL, COL1A2, DCN, ELN and RUNX2. Used in agglomerative cluster analysis, they correctly grouped the bone-forming cell populations as distinct. Although donor #6 cells were correlation slope outliers, they contrastingly formed bone without showing ex vivo mineralization. Mathematical expression level normalization of the most discrepantly upregulated signature gene COL1A2, sufficed to cluster donor #6 with the bone-forming classification. Moreover, attenuating factors causing genuine COL1A2 gene down-regulation, restored ex vivo mineralization. This suggested that the signature gene had an osteogenically influential role; nonetheless no single biomarker was fully deterministic whereas all five signature genes together led to accurate cluster analysis. We show proof of principle for an osteogenic potency assay providing early characterization of primary cGMP-hBM-MSC cultures according to their donor-specific bone-forming potential.


2016 - Prevalence and risk factors for microalbuminuria in children and adolescents with type 1 diabetes: long-term experience of a single centre [Abstract in Rivista]
Iughetti, Lorenzo; Bruzzi, Patrizia; Dozza, Alessandra; Boncompagni, Alessandra; Cenciarelli, Valentina; Mazzoni, Silvia; Lucaccioni, Laura; Predieri, Barbara
abstract

Objectives: Diabetic nephropathy is a late complication of type 1 diabetes mellitus (T1DM) and microalbuminuria (MA) is an early and reversible sign of diabetic renal disease. Aims of this longitudinal study were: to define the prevalence of MA in children and adolescents with T1DM; to identify which risk factors are predictive for the development of MA. Methods: Seventy children and adolescents with T1DM [57% male; age at T1DM onset (T0) 5.95 3.16 yrs] were enrolled. The mean follow-up (FU) period was 7.18 1.89 yrs. Blood and urinary tests were performed once a year from the T0. MA screening was evaluated by urinary albumin concentration (UAC) or by timed urine collections for urinary albumin/creatinine ratio (ACR). MA was considered persistent (PMA) when at least 2 out of 3 consecutive evaluation of UAC and/or ACR were found positive. Results: PMA was found in 13% of patients. Subjects with PMA compared to normoalbuminuric ones had both significantly higher GFR at T0 (p = 0.025) and UAC at 1-year FU (T1) (p = 0.045). Predictive cut-off values for PMA development were 160 ml/min/1.73 m2 for GFR at T0 (sensitivity: 57%, specificity: 75%) and 8.5 mg/L for UAC at T1 (sensitivity:75%, specificity:80%). Relative risk for PMA was 23-times higher when UAC was >8.5 mg/L (p = 0.004). Kaplan- Meier survival curves as a function of age at T0 showed an increased probability of developing PMA among children in which T1DM onset occured between 5 and 11 years of age compared to those with younger onset (p = 0.014) and a pubertal diabetes duration >5 years was also a significant risk factor for PMA (p < 0.0005). Conclusions: Age at T1DM onset, pubertal timing, high UAC, and hyperfiltration predispose to PMA development and increase the risk for diabetic nephropathy. Specific cut-off values at T1DM onset and during first years of FU could provide indications to avoid disease progression.


2016 - Streptococcus pneumoniae oropharyngeal colonization in school-age children and adolescents with type 1 diabetes mellitus: Impact of the heptavalent pneumococcal conjugate vaccine. [Articolo su rivista]
Principi, N; Iughetti, Lorenzo; Cappa, M; Maffeis, C; Chiarelli, F; Bona, G; Gambino, M; Ruggiero, L; Patianna, V; Matteoli, Mc; Marigliano, M; Cipriano, P; Parlamento, S; Esposito, S; Italian Pneumococcal Study Group on, Diabetes
abstract

This study evaluated Streptococcus pneumoniae colonization in children and adolescents with type 1 diabetes mellitus (DM1) to investigate the theoretical risk of invasive pneumococcal disease (IPD) in these patients and the potential protective efficacy of pneumococcal conjugate vaccines (PCVs). An oropharyngeal swab was obtained from 299 patients aged 6-17 y with DM1 who were enrolled during routine clinical visits. DNA from swabs was analyzed for S. pneumoniae using real-time polymerase chain reaction. S. pneumoniae was identified in the swabs of 148 subjects (49.8%). Colonization was strictly age-related and declined significantly in the group aged ≥15 years (odds ratio [OR] 0.28; 95% confidence interval [CI], 0.14-0.57). Carriage was also significantly influenced by sex (lower in females: OR 0.56; 95% CI, 0.35-0.91), ethnicity (less common among non-Caucasians: OR 0.34; 95% CI, 0.13-0.89), parental smoking habit (more frequent among children with at least one smoker between parents: OR 1.76; 95% CI, 0.90-2.07), and the administration of antibiotic therapy in the previous 3 months (less frequent among patients who received antibiotics: OR 0.21; 95% CI, 0.07-0.62). Multivariate analyses of the entire study population showed no association between carriage and PCV7 vaccination status. Serotypes 19F, 9V, and 4 were the most frequently identified serotypes. In conclusion, school-age children and adolescents with DM1 are frequently colonized by S. pneumoniae, and protection against pneumococcal carriage following infant and toddler vaccination was not effective after several years. Together with the need to increase vaccine uptake in all the children aged &lt;2 years, these results suggest that PCV booster doses are needed in DM1 patients to maintain the protection offered by these vaccinations.


2016 - Sudden unexpected post natal collapse [Articolo su rivista]
Bariola, Maraia Carolina; Roncuzzi, Francesca; Ferrari, Fabrizio; Iughetti, Lorenzo
abstract

Evento raro ma estremamente grave: conduce a morte nel 33-50% dei casi e a disabilità grave nella maggior parte dei sopravvissuti. Recenti studi suggeriscono l’importanza dell’ipotermia terapeutica, nel miglioramento dell’outcome neurologico dei bambini che hanno presentato collasso post-natale


2016 - The Efficacy of Insulin Degludec in Children and Adolescents with Type 1 Diabetes [Abstract in Rivista]
Bruzzi, Patrizia; Maltoni, Giulio; Predieri, Barbara; Zucchini, Stefano; Iughetti, Lorenzo
abstract

Insulin degludec (IDeg; Tresibaw) is a novel basal insulin with an ultra-long, flat and stable action profile. In adults, it provides a more consistent glucose-lowering effect and lower rates of hypoglycaemia than glargine (IGlar). Data on children and adolescents are scarce.


2016 - The measurement of urinary gonadotropins for assessment and management of pubertal disorder [Articolo su rivista]
Lucaccioni, Laura; Mcneilly, Jane; Mason, Avril; Giacomozzi, Claudio; Kyriakou, Andreas; Guftar Shaikh, Mohammed; Iughetti, Lorenzo; Faisal Ahmed, Syed
abstract

OBJECTIVE: Measurement of urinary LH (uLH) and FSH (uFSH) may facilitate non-invasive pubertal assessment but there is a need for further validation by studying children and adolescents with disorders of puberty. DESIGN: 65 cases (Male: 25) with a median age of 12 years (2.9-18.1) supplied at least one non-timed urine sample for uLH and uFSH measurement by immunoassay and corrected for creatinine excretion. 25 cases were receiving GnRH-agonist (GnRH-a) at the time of sample collection. In 41 cases, urine samples were collected prior to a LH RH test and in 12 cases matched serum samples for basal LH (sLH) and FSH (sFSH) were also available. RESULTS: There was a significant correlation between sLH and uLH: uCr (r=0.82; p-value &lt;0.001) and sFSH and uFSH: uCr (r=0.93; p-value &lt;0.001). Based on receiver operator characteristics analysis, a uLH : uCr value of 0.05 IU/mmol as a cut-off would detect a LH peak &gt;5U I/L with a sensitivity of 86% and a specificity of 72% with a positive predictive value of 93%. In pubertal boys (6) and girls (22) with a sLH peak &gt;5UI/L, median uLH: uCr was 0.27 IU/mmol (0.27-0.28) and 0.17 IU/mmol (0.09-0.43), respectively. The median uFSH: uCr was 0.51 IU/mmol (0.41-0.60) for boys and 1.1 IU/mmol (0.21-2.44) for girls. In the 25 cases on GnRH-a, the median uLH : uCr for boys and girls was 0.02 IU/mmol (0.01-0.02) and 0.02 IU/mmol (0.004-0.07), respectively, and the median uFSH: uCr was 0.07 IU/mmol (0.05-0.09) and 0.27 IU/mmol (0.09-0.54), respectively. CONCLUSION: Urinary gonadotrophins reflect serum gonadotrophin concentration and may represent a reliable non-invasive method of assessing pubertal progress.


2016 - The Metabolic Negative Effect of Gonadotropin-Releasing Hormone Agonist Therapy in Childhood: Is it Short-Term and Reversible? [Abstract in Rivista]
Iughetti, Lorenzo; Bruzzi, Patrizia; Bigi, Elena; Valeri, Lara; Manzotti, Elena; Predieri, Barbara
abstract

It is known that early sexual maturation contributes to an adverse metabolic programming. Our results support a direct and negative effect of GnRHa per se on BMI, glycaemic metabolism and lipid profile in children affected by CPP.Nevertheless, these consequences appear to be short-term and reversible.


2016 - The Role of 24-h Ambulatory Blood Pressure Monitoring in Children and Adolescents with Type 1 Diabetes: Early Experience of a Single Centre [Abstract in Rivista]
Predieri, Barbara; Bruzzi, Patrizia; Bianco, Valentina; Spaggiari, Valentina; Mazzoni, Silvia; Cattelani, Chiara; Iughetti, Lorenzo
abstract

Ambulatory blood pressure monitoring (ABPM) permits the observation of blood pressure (BP) in a nonmedical environment. In adults, ABPM is better related to renal damage and cardiovascular morbidity than office BP readings. In early stages of type 1 diabetes (T1DM), the role of ABPM is still controversial.


2016 - Torcicollo A Tuttalè! (Note) Coccolini, E.a, Bruzzi, P.b, Bergonzini, P.b, Iughetti, L.ab [Articolo su rivista]
Coccolini, Elena; Bruzzi, Patrizia; Bergonzini, P; Iughetti, Lorenzo
abstract

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2016 - UNA MANO TROPPO BIANCA [Abstract in Rivista]
Cattelani, Chiara; Mazzoni, Silvia; Ferrari, Fabrizio; Iughetti, Lorenzo
abstract

La leucemia neonatale/congenita (esordio entro i 30 giorni di vita) è rara; meno dell’1% dei casi di leucemia infantile sono, infatti, diagnosticati nei neonati, con stime di incidenza di 1-5 casi per milione di nati vivi.


2016 - UNA PANCREATITE ATIPICA [Abstract in Rivista]
Mazzoni, Silvia; Cattelani, Chiara; Iughetti, Lorenzo
abstract

La diagnosi precoce anche nelle MK atipiche/incomplete è fondamentale, considerando che la prognosi è legata all’inizio tempestivo della terapia, in grado di ridurre il rischio di insorgenza di anomalie coronariche.


2016 - Una pancreatite atipica... [Abstract in Rivista]
Cenciarelli, Valentina; Roncuzzi, Francesca; Di Biase, Anna Rita; Iughetti, Lorenzo
abstract

La m. di Kawasaki si può manifestare in modi e con sintomi diversi


2016 - Unusual presentation of Rosai-Dorfman disease in a 14-month-old Italian child: a case report and review of the literature [Articolo su rivista]
Di Dio, Francesco; Mariotti, Ilaria; Coccolini, Elena; Bruzzi, Patrizia; Predieri, Barbara; Iughetti, Lorenzo
abstract

Background: Rosai-Dorfman disease (RDD) is a rare form of histiocytosis characterized by histiocyte proliferation within lymph nodes and extranodal tissue. Here we report an unusual presentation of RDD in an Italian toddler. Moreover, we reviewed the pediatric case reports published between 2004 and 2014, focusing in particular on medical therapy. Case presentation: We report the case of a 14-month-old child who developed a progressive swelling of the right parotid, associated with systemic symptoms and abnormal blood tests. During diagnostic work-up, cervical, intraparotid, and unilateral hilar lymphadenopathies were found. Histopathological and immunohistochemistry studies of a cervical lymph node biopsy established the diagnosis of RDD, with positive PCR for Epstein - Barr virus on the biopsy specimen. Oral steroid therapy was started with progressive reduction in size of all lesions, resolution of systemic symptoms, and normalization of blood tests. Conclusion: RDD is generally considered a benign and self-limiting form of histiocytosis, usually associated with favorable prognosis. However, complications are not infrequent and fatal cases were reported even in children. Efforts should be made to establish the best therapeutic strategy for this disease, as no well-defined guidelines exist. Finally, RDD should be included in differential diagnosis of lymphadenopathy and parotid swelling even in very young children.


2015 - Aetiological Diagnosis of Diabetes in Italian Diabetic Children and Adolescents [Abstract in Rivista]
Delvecchio, Maurizio; Salzano, Giuseppina; Mozzillo, Enza; Frontino, Giulio; Patera, Patrizia; Toni, Sonia; Rabbone, Ivana; Cherubini, Valentino; Tumini, Stefano; D’Annunzio, Giuseppe; Iughetti, Lorenzo; Maltoni, Giulio; Cauvin, Vittoria; Marigliano, Marco; Barbetti, Fabrizio
abstract

Similarly to other countries, T1D is the most frequent diagnosis in Italian diabetic patients !18 years, while a striking disparity, likely due to different lifestyle and genetic background, is observed between the rate of T2D of this study (1.1%, in keeping with European reports of 0.24–1.4%) and the SEARCH data from US (about 11%). At further variance with other Western countries (e.g. Norwegian registry, the DPV-Wiss study, the SEARCH study), the prevalence of MD in Italy is very high. This could depend on the fact that broader attention is devoted to MD in Italy than in the US, and also on the fact that genetic testing is easily accessible and free of charge. The close follow-up of patients with incidental hyperglycemia likely accounts for the very high rate of GCK/MODY2 mutations, the most frequent MODY type in Italy.


2015 - Bullying and Victimization in Overweight and Obese Outpatient Children and Adolescents: An Italian Multicentric Study [Articolo su rivista]
Bacchini, D; Licenziati, Mr; Garrasi, A; Corciulo, N; Driul, D; Tanas, R; Fiumani, P. M.; Di Pietro, E; Pesce, S; Crinò, A; Maltoni, G; Iughetti, Lorenzo; Sartorio, A; Deiana, M; Lombardi, F; Valerio, G.
abstract

Objective Being overweight or obese is one of the most common reasons that children and adolescents are teased at school. We carried out a study in order to investigate: i) the relation between weight status and school bullying and ii) the relation between weight status categories and types of victimization and bullying in an outpatient sample of Italian children and adolescents with different degrees of overweight from minimal overweight up to severe obesity. Participants/Methods Nine-hundred-forty-seven outpatient children and adolescents (age range 6.0'14.0 years) were recruited in 14 hospitals distributed over the country of Italy. The participants were classified as normal-weight (N = 129), overweight (N = 126), moderately obese (N = 568), and severely obese (N = 124). The nature and extent of verbal, physical and relational bullying and victimization were assessed with an adapted version of the revised Olweus bully-victim questionnaire. Each participant was coded as bully, victim, bully-victim, or not involved. Results Normal-weight and overweight participants were less involved in bullying than obese participants; severely obese males were more involved in the double role of bully and victim. Severely obese children and adolescents suffered not only from verbal victimization but also from physical victimization and exclusion from group activities. Weight status categories were not directly related to bullying behaviour; however severely obese males perpetrated more bullying behaviour compared to severely obese females. Conclusions Obesity and bullying among children and adolescents are of ongoing concern worldwide and may be closely related. Common strategies of intervention are needed to cope with these two social health challenges.


2015 - Central Precocious Puberty in Cerebral Palsy [Abstract in Rivista]
Bruzzi, Patrizia; Messina, Maria Francesca; Bartoli, Alessandra; Lucaccioni, Laura; Predieri, Barbara; De Luca, Filippo; Iughetti, Lorenzo
abstract

Children affected by cerebral palsy (CP) could experience central precocious puberty (CPP) 20 times more than general population. Nevertheless, the treatment is challenging.


2015 - Childhood obesity and environmental pollutants: a dual relationship [Articolo su rivista]
Iughetti, Lorenzo; Lucaccioni, Laura; Predieri, Barbara
abstract

The rise in obesity rates is an alarming global health concern. Despite obesity is mainly due to an unbalanced energy intake and expenditure, several recent studies suggest that it could be a consequence of exposure during critical developmental windows to environmental chemicals disrupting endocrine functions. This suggests that a shift is occurring in the human body pathways used to integrate changing nutritional and environmental variables and to maintain metabolic balance and body weight. This review highlights the role of pesticides, in particular endocrine disrupter ones, on obesity pathogenesis in childhood and summarizes the current under-standing of the major environmental influences on pediatric obesity. (www.actabiomedica.it).


2015 - Circulating miR146a and 486-5p are Altered in Obese Children with and Without Non-Alcoholic Fatty LiverDisease (NAFLD) and Correlate with Abdominal Fat and BMI [Abstract in Rivista]
Montanini, Luisa; Patianna, VIVIANA DORA; Sartori, Chiara; Predieri, Barbara; Bruzzi, Patrizia; Lazzeroni, Pietro; Merli, Silvia; Bergamaschi, Paolo; Bernasconi, Sergio; Iughetti, Lorenzo; Street, maria Elisabeth
abstract

Specific circulating miRNAs show changes in obesity and miR-146a shows clear relationships with BMI, distribution of adiposity and parameters of insulin sensitivity


2015 - Continuous subcutaneous insulin infusion in Italy: third national survey [Articolo su rivista]
Bruttomesso, D; Laviola, L; Lepore, G; Bonfanti, R; Bozzetto, L; Corsi, A; Di Blasi, V; Girelli, A; Grassi, G; Iafusco, D; Rabbone, I; Schiaffini, R; Italian Study Group Diffusion, Csii; Iughetti, Lorenzo; Predieri, Barbara
abstract

Background: Continuous subcutaneous insulin infusion (CSII) is increasing worldwide, mostly because of improved technology. The aim of this study was to evaluate the current status of CSII in Italy. Materials and Methods: Physicians from 272 diabetes centers received a questionnaire investigating clinical features, pump technology, and management of patients on CSII. Results: Two hundred seventeen centers (79.8%) joined the study and, by the end of April 2013, gave information about 10,152 patients treated with CSII: 98.2% with type 1 diabetes mellitus, 81.4% adults, 57% female, and 61% with a conventional pump versus 39% with a sensor-augmented pump. CSII advanced functions were used by 68% of patients, and glucose sensors were used 12 days per month on average. Fifty-eight percent of diabetes centers had more than 20 patients on CSII, but there were differences among centers and among regions. The main indication for CSII was poor glucose control. Dropout was mainly due to pump wearability or nonoptimal glycemic control. Twenty-four hour assistance was guaranteed in 81% of centers. A full diabetes team (physician+nurse+dietician+psychologist) was available in 23% of adult-care diabetes centers and in 53% of pediatric diabetes units. Conclusions: CSII keeps increasing in Italy. More work is needed to ensure uniform treatment strategies throughout the country and to improve pump use.


2015 - Effects of Exercise in Children and Adolescent with Type 1 Diabetes Mellitus [Articolo su rivista]
Iughetti, Lorenzo; Gavioli, Sara; Bonetti, Annalisa; Predieri, Barbara
abstract

Exercise is one of the most important components, together with insulin therapy and diet, in the clinical management of type 1 diabetes mellitus (T1DM). Physical activity has multiple health benefits, like blood pressure reduction, improvement of cardiovascular fitness and lipoprotein profile. The benefits for children with diabetes may also include positive effects on glycemic metabolism. The following review examines the main studies about the effects of exercise on diabetes. Additional longitudinal studies are needed to verify the hypothetical positive relationship between sport and T1DM and between sport and diabetic complications. However, aerobic and moderate intensity physical activity in children and adolescents with T1DM should be encouraged also for its beneficial psychological effects.


2015 - Evaluation of Cardiovascular Risk in Childhood: Data from a Survey of Dyslipidaemic Children [Abstract in Rivista]
Bruzzi, Patrizia; Colombini, Giulia; Lucaccioni, Laura; Predieri, Barbara; Iughetti, Lorenzo
abstract

Dyslipidaemia is a well-known risk factor in developing cardiovascular disease (CVD) already in childhood.


2015 - Familial Short Stature Associated to Terminal Microdeletion of 15q26.3: Variable Phenotype not Involving the IGF1 Receptor Gene [Abstract in Rivista]
Lucaccioni, Laura; Madeo, Simona Filomena; Stanghellini, Ilaria; Bruzzi, Bruzzi; Predieri, Bruzzi; Iughetti, Lorenzo; Percesepe, Antonio
abstract

Terminal deletions of chromosome 15q are associated with different degrees of pre- and post-natal growth failure, dysmorphic features, functional impairments and congenital anomalies. Although monosomies of 15q26 do not represent a classical contiguous gene syndrome, candidate genes for selected features have been identified. Short stature is referred to deletions of the IGF1-R gene, located on 15q26.3. We demonstrate evidence of phenotype comparable with 15q26 monosomy in a family with microdeletion of 15q26.3 not involving IGF1-R gene.


2015 - Glycemic Control in Kenyan Children and Adolescents with Type 1 Diabetes Mellitus [Articolo su rivista]
Ngwiri, Thomas; Were, Fred; Predieri, Barbara; Ngugi, Paul; Iughetti, Lorenzo
abstract

Background. Type 1 diabetes mellitus (T1DM) is the most common endocrine disorder in children and adolescents worldwide. While data about prevalence, treatment, and complications are recorded in many countries, few data exist for Sub-Saharan Africa. The aim of this study was to determine the degree of control in patients with T1DM aged 1–19 years over a 6-month period in 3 outpatient Kenyan clinics. It also sought to determine how control was influenced by parameters of patient and treatment. Methods. Eighty-two children and adolescents with T1DM were included in the study. Clinical history regarding duration of illness, type and dose of insulin, and recent symptoms of hypoglycemia/hyperglycemiawere recorded. Glycaemia, HbA1c, and ketonuria were tested. HbA1c of 8.0% and below was defined as the cut-off for acceptable control. Results. The median HbA1c for the study population was 11.1% (range: 6.3–18.8). Overall, only 28% of patients had reasonable glycemic control as defined in this study. 72% therefore had poor control. It was also found that age above 12 years was significantly associated with poor control. Conclusions. African children and with T1DM are poorly controlled particularly in adolescents. Our data strongly support the necessity of Kenya children to receive more aggressive management and follow-up.


2015 - Growth hormone treatment of adolescents with growth hormone deficiency (GHD) during the transition period: results of a survey among adult and paediatric endocrinologists from Italy. Endorsed by SIEDP/ISPED, AME, SIE, SIMA [Articolo su rivista]
Aimaretti, G; Attanasio, R; Cannavò, S; Nicoletti, Mc; Castello, R; Di Somma, C; Garofalo, P; Iughetti, Lorenzo; Loche, S; Maghnie, M; Mazzanti, L; Saggese, G; Salerno, M; Tonini, G; Toscano, V; Zucchini, S; Cappa, M.
abstract

Treatment of adolescents with growth hormone deficiency (GHD) during the transition period is a controversial issue. This paper is a contribution from the Italian community of paediatric and adult endocrinologists surveyed in a Delphi panel. The Delphi method is a structured communication technique, originally developed as a systematic, interactive forecasting method that relies on a panel of experts. The experts answer questionnaires in two or more rounds. There was substantial agreement on the definition of the problems associated with the diagnosis and treatment of adolescents with GHD in the transition period, as well as on the identification of the controversial issues which need further studies. There is general consensus on the need of re-testing all isolated idiopathic GHD after at least 30-day withdrawn from treatment, while in patients with multiple pituitary deficiency and low IGF-I levels there is generally no need to re-test. In patients with permanent or confirmed GHD, a starting low rhGH dose (0.01-0.03 mg per day) to be adjusted according to IGF-I concentrations is also widely accepted. For those continuing treatment, the optimal therapeutic schedule to obtain full somatic maturation, normalization of body composition and bone density, cardiovascular function and Quality of Life, need to be evaluated.


2015 - High Levels of Perfluorooctane Sulfonate in Children at the Onset of Diabetes [Articolo su rivista]
Predieri, Barbara; Iughetti, Lorenzo; Guerranti, Cristiana; Bruzzi, Patrizia; Perra, Guido; Focardi, Silvano E.
abstract

Background. Impairments of endocrine system may be associated with exposure to perfluorinated compounds that are able to bind nuclear receptors, including the peroxisome proliferator-activating receptors. Aim of this study was to assess perfluorooctane sulfonate and perfluorooctanoic acid concentrations in children and adolescents at the onset of type 1 diabetes compared to healthy controls. Methods. Forty-four children and adolescents were recruited and subdivided into two groups: (A) 25 subjects with type 1 diabetes and (B) 19 healthy controls. Perfluorinated compounds were measured using high performance liquid chromatography with electrospray ionization tandem mass spectrometry. Nonparametric statistical analysis was performed. Results. Perfluorooctane sulfonate concentrations were significantly higher in patients with type 1 diabetes compared to controls (1.53 ± 1.50 versus 0.55 ± 0.15 ng/mL, resp.; p < 0.001). Multivariate linear regression analysis identified lipid levels as significant predictive factors for perfluorooctane sulfonate levels. Conclusions. Our data suggests that higher serum levels of perfluorooctane sulfonate may be considered a biomarker of exposure and susceptibility to develop type 1 diabetes.


2015 - Human Placenta-Derived Mesenchymal Stem Cells: A Novel Protocol for Pancreatic Differentiation [Abstract in Rivista]
Patianna, VIVIANA DORA; Okere, Bernard; Predieri, Barbara; Bruzzi, Patrizia; Iughetti, Lorenzo
abstract

The present study shows that placenta-derived mesenchymal cells can be isolated and expanded in medium supplemented with HPL. Due to the easy accessibility, lack of ethical concerns and abundant availability AMSC might be an attractive, alternative source of progenitor/stem cells for basic or translational research and a reliable source of insulin producing cells in clinical applications.


2015 - Hypercholesterolemia in Childhood [Capitolo/Saggio]
Iughetti, Lorenzo; Predieri, Barbara; Bruzzi, Patrizia
abstract

The American Heart Association (AHA), endorsed by the American Academy of Pediatrics (AAP), identified 8 high-risk pediatric diagnosis and developed practical recommendations for the management of cardiovascular risk.. The selected diseases comprise familial hypercholesterolemia (FH), together with diabetes mellitus (type 1 and 2), chronic kidney disease, heart transplantation, Kawasaki disease, congenital heart disease, chronic inflammatory disease and childhood cancer. Subclinical endothelia dysfunction, measured through non-invasive surrogate methods such as flow-mediated dilation (FMD), occurs early in FH children indicating an increased risk for premature CVD and reflecting the need for early initiation of anticholesterolemic treatment. Moreover, increasing evidences indicate that, in high-risk conditions as well as in most children with a minor degree of vascular involvement, appropriate therapy could prevent and/or reverse the progression of these cardiovascular changes]. Therefore, the identification and the management of hypercholesterolemia in children are of great consequence.


2015 - In vitro differentiation of human amniotic epithelial cells into insulin-producing 3D spheroids [Articolo su rivista]
Okere, Bernard; Alviano, Francesco; Costa, Roberta; Quaglino, Daniela; Ricci, Francesca; Dominici, Massimo; Paolucci, Paolo; Bonsi, Laura; Iughetti, Lorenzo
abstract

Regenerative medicine and stem cell therapy may represent the solution for the treatment of non-curable human diseases such as type 1 diabetes. In this context of growing demand for functional and safe stem cells, human amniotic epithelial cells (hAECs) from term placenta have attracted increasing interest for their wide availability, stem cell properties, and differentiation plasticity, which make them a promising tool for stem cell-based therapeutic applications. We initially assayed the stemness characteristics of hAECs in serum-free conditions. Subsequently we developed a culture procedure on extracellular matrix for the formation of three-dimensional (3D) spheroids. Finally, we tested the immunomodulation and differentiation potential of hAEC spheroids: the presence of pancreatic endocrine hormones was revealed with transmission electron microscopy and immunofluorescence analyses; the release of C-peptide in hyperglycemic conditions was assayed with ELISA.The serum-free culture conditions we applied proved to maintain the basic stemness characteristics of hAECs. We also demonstrated that 3D spheroids formed by hAECs in extracellular matrix can be induced to differentiate into insulin-producing cells. Finally, we proved that control and induced cells equally inhibit the proliferation of activated mononuclear cells.The results of this study highlight the properties of amnion derived epithelial cells as promising and abundant source for cell-based therapies. In particular we are the first group to show the in vitro pancreatic induction of hAECs cultured on extracellular matrix in a 3D fashion. We accordingly propose the outcomes of this study as a novel contribution to the development of future cell replacement therapies involving placenta-derived cells.


2015 - Interaction between Streptococcus pneumoniae and Staphylococcus aureus in paediatric patients suffering from an underlying chronic disease [Articolo su rivista]
Esposito, S; Marseglia, Gl; Colombo, C; Iughetti, Lorenzo; Terranova, L; Ierardi, V; Gambino, M; Principi, N.
abstract

Little is known about the interaction between Streptococcus pneumoniae and Staphylococcus aureus in school-age children and adolescents suffering from an underlying chronic disease. To increase our knowledge in this regard, an oropharyngeal swab was obtained from school-age children and adolescents suffering from asthma (n = 423), cystic fibrosis (CF) (n = 212) and type 1 diabetes mellitus (DM1) (n = 296). S. pneumoniae detection and serotyping were performed using a real-time polymerase chain reaction, and S. aureus detection was performed using the RIDAGENE MRSA system. Among asthmatic, CF and DM1 patients, both pathogens were identified in 65/423 (15.4%), 21/212 (9.9%) and 62/296 (20.9%) children, respectively; S. pneumoniae alone was identified in 127/434 (30.0%), 21/212 (9.9%) and 86/296 (29.1%), respectively; S. aureus alone was identified in 58/434 (13.7%), 78/212 (36.8%) and 49/296 (16.6%), respectively. S. pneumoniae colonisation rates were higher in younger children and declined with age, whereas the frequency of S. aureus colonisation was quite similar in the different age groups. Among asthmatic and CF patients aged 6-9 years, S. aureus carriage was significantly higher in children who were positive for S. pneumoniae (P <0.05). No significant association emerged between S. aureus carriage and carriage of S. pneumoniae serotypes included in the pneumococcal conjugate vaccines (PCVs). This study shows for the first time that school-age children and adolescents with asthma, CF and DM1 are frequently colonised by S. pneumoniae and S. aureus and that no negative relationship seems to exist between these pathogens. Moreover, the supposed protection offered by PCV administration against S. aureus colonisation was not demonstrated.


2015 - Influence of the Application of the POI Score on the Results of GH Therapy in Prader-Willi [Abstract in Rivista]
Salvatoni, Alessandro; Bocchini, Sarah; Crino`, Antonino; Di Candia, Stefania; Grugni, Graziano; Iughetti, Lorenzo; Nespoli, Luigi; Nosetti, Luana; Padoan, Giovanni; Pilotta, Alba; Piran, Marzia; Spica Russotto, Valeria
abstract

According to international guidelines Prader-Willi children during GH treatment must be closely monitored by polysomnography, ENT evaluation and IGF1 levels.


2015 - La terapia insulinica sottocutanea continua (CSII) in Italia. Terza indagine nazionale [Subcutaneous insulin infusion (CSII) in italy: The third national survey] [Articolo su rivista]
Bruttomesso, D; Laviola, L; Lepore, G; Bonfanti, R; Bozzetto, L; Corsi, A; Di Blasi, V; Girelli, A; Grassi, G; Iafusco, D; Rabbone, I; Schiaffini, R; Montani, V; Colleluori, P; Paciotti, V; Alfidi, P; Grosso, J; Tumini, S; Cipriano, P; Vitacolonna, E; Di Vieste, G; Minnucci, A; Antenucci, D; La Penna, G; Taraborrelli, M; Macerala, B; Citro, G; De Morelli, G; Gnasso, A; Irace, C; Citriniti, F; Lazzaro, N; Bruzzese, M; Mammì, F; De Berardinis, F; Santoro, E; Corigliano, G; Corigliano, M; Parillo, M; Schettino, M; Di Blasi, V; Fresa, R; Annuzzi, G; Bozzetto, L; Bassi, V; Santinelli, C; Buono, P; Mozzillo, E; Corigliano, G; Russo, V; Esposito, K; Petrizzo, M; Foglia, A; Gatti, A; Gentile, S; Guarino, G; Iafusco, D; Zanfardino, A; Lambiase, C; Vitale, A; Zucchini, S; Maltoni, G; Forlani, G; Moscatiello, S; Suprani, T; Bensa, M; Tomasi, F; Monesi, M; Nizzoli, M; Acquati, S; Chierici, G; Milli, B; Iughetti, Lorenzo; Predieri, Barbara; Cavani, R; Romano, S; Manicardi, V; Michelini, M; Cimicchi, M. C; Ugolotti, D; Zavaroni, I.; Dei Cas, A; Dall’Aglio, E; Papi, M; Tardio, S; Calderini, M; Riboni, S; D’Amato, L; Zavaroni, D; Gastaldi, L; Cirillo, A; Di Bartolo, P; Pellicano, F; Di Seclì, C; Manicardi, V; Amarri, S; Lasagni, A; Marsciani, A; Pedini, A; Pagliani, U; Rossi, C; Tortul, C; Brunato, B; Assaloni, R; Zanette, G; Livolsi, P; Petrucco, A; Tercelj, K; Manca, E; Candido, R; Tommasi, E; Tornese, G; Faleschini, E; Tonutti, L; Agus, S; Zanatta, M; Rosolen, A; Comici, A; Falasca, P; Graziano, F. M; Misischi, I; Forte, E; Palmacci, C; Tuccinardi, F; Ricciardi, G. P; Di Masa, P; Ragonese, M; Cipolloni, L; Buzzetti, R; Moretti, C; Leto, G; Crinò, A; Bocchini, S; Pozzilli, P; Maurizi, A. R; Di Perna, P; Giuliano, M; Frontoni, S; Malandrucco, I; Pitocco, D; Scalpone, R; Toscanella, F; Schiaffini, R; Cappa, M; Ventura, C; Bonato, V; De Bernardinis, M; Cavallo, M. G; Leonetti, F; Morano, S; Mandosi, E; Cicconetti, E; Ciampittiello, G; Marini, M. A; Sabato, D; Lauro, D; Napoli, A; Giraudo, F; Toscano, V; Pugliese, G; Massimiani, F; Fava, D; Gargiulo, P; Mecca, N; Tubili, C; Nardone, M. R; Morviducci, L; Manca Bitti, M. L; Arcano, S; Leotta, S; Suraci, C; Chiaramonte, F; Visalli, N; Strollo, F; Arnaldi, C; Tosini, D; Corsi, A; Ponzani, P; Patrone, M; Guido, R; Aglialoro, A; Ghisoni, G; Fabbri, F; Bordone, C; Maggi, D; Cordera, R; Minuto, N; Rotondo, E; Speranza, D; Siri, M; Carro, S; Zappa, A; Parmigiani, S; Nieri, S; Briatore, L; Calvo, G; Querci, F; Lepore, G; Trevisan, R; Girelli, A; Bonfadini, S; Prandi, E; Felappi, B; Locatelli, F; Fuso, V; Rocca, A; Meneghini, E; Massafra, C; Terni, T; Elli, P; Ruggeri, P; Carrai, E; Musacchio, N; Marelli, G; Vilei, V; Richini, D; Inversini, C; Franzetti, I; Bonacina, M; Ciucci, A; Sciangula, L; Duratorre, E; Bonomo, M; Bertuzzi, F; Chebat, E; Muratori, M; Scaramuzza, A; Zuccotti, G. V; Bollati, P. M; Colapinto, P; Orsi, E; Palmieri, E; Laurenzi, A; Molinari, C; Bonfanti, R; Frontino, G; Veronelli, A; Zecchini, B; Bianchi, A; Torchio, G; Lovati, E; Ghilardi, G; Dagani, R; Berra, C; Fochesato, E; Pissarelli, A; Bucciarelli, L; Bulgheroni, M; Guerraggio, L; Zonca, S; Bossi, A. C; Berzi, D; Mangone, I; Cazzaniga, E; Rabini, R. A; Boemi, M; Faloia, E; Boscaro, M; Sternari, G; Iannilli, A; Cherubini, V; Tinti, G; Manfrini, S; Tesei, A. M; Maolo, G; Galetta, M; Vespasiani, G; Busciantella Ricci, N; Cartechini, M. G; Aiello, A; Di Vincenzo, S; Vitale, C; Di Caro, P; Lera, R; Secco, A; Lesina, A; Romeo, F; Origlia, C; Giorda, C.; Chiambretti, A. M; Fornengo, R; De Donno, V; Gallarotti, F; Manti, R; Marafetti, L; Cadario, F; Savastio, S; Barbieri, P; Massucco, P; Alì, A; Gottero, C; Degiovanni, M; Bertaina, S; Grassi, G; Maghenzani, G; Rabbone, I; Tinti, D; Fontana, F; Giorgino, F; Stefanelli, G; Cavallo, L; Zecchino, C; Piccinno, E; Ortolani, F; Gallo, F; Moramarco, F; Marino, A; Sparasci, G; Mileti, G; Lamacchia, O; Picca, G; Coccioli, M. S; Micale, F; Serra, R; R
abstract

Continuous subcutaneous insulin infusion (CSII) is increasingly being used worldwide, mostly thanks to technical improvements. This study examined the current status of CSII in Italy. Physicians in charge of 272 diabetes centers caring for patients using CSII were sent a questionnaire investigating clinical features, pump technology and management of these patients; a large proportion (217 centers, 79.8%) joined the study. By end-April 2013, data had been collected on 10152 patients treated with CSII; 98.2% had type 1 diabetes, 82.4% were adults, 57% female. Only just over half the centers (59%) managed more than 20 CSII patients each. The distribution of patients varied widely both among and within different regions. The main indication for CSII was the de- sire to improve glycemic control. Dropouts (8.65%) were mainly due to difficulties with pump wearability or non-optimal glycemic control. Among CSII patients 61% used a traditional pump, 39% a sensor augmented pump. Only 68% used the CSII advanced functions and glucose sensors were used twelve days per month on average. Round-the-clock assistance was guaranteed in 81% of centers; a full diabetes team followed patients in only 40% of adult-care centers and 50% of pediatric units. CSII is increasingly used in Italy, by adults and pediatric patients. However, further work is needed to unify treatment strategies throughout the country and to encourage optimal pump use and applications.


2015 - Metamorphic Thyroid Autoimmunity in Down Syndrome: From Hashimoto’s Thyroiditis to Graves’ Disease and Beyond [Abstract in Rivista]
Aversa, Tommaso; Valenzise, Mariella; Salerno, Mariacarolina; Corrias, Andrea; Iughetti, Lorenzo; Radetti, Giorgio; De Luca, Filippo; Wasniewska, Malgorzata
abstract

DS children may be incline to manifest over time a phenotypic metamorphosis from HT to GD; ii) A share of GD children with DS may subsequently fluctuate from hyperthyroidism to hypothyroidism; iii) In DS HT presentation is absolutely peculiar; iv) in DS GD is characterized by a mild biochemical and clinical course.


2015 - Metamorphic thyroid autoimmunity in Down Syndrome: from Hashimoto's thyroiditis to Graves' disease and beyond [Articolo su rivista]
Aversa, Tommaso; Valenzise, Mariella; Salerno, Mariacarolina; Corrias, Andrea; Iughetti, Lorenzo; Radetti, Giorgio; De Luca, Filippo; Wasniewska, Malgorzata
abstract

Background: It is known that Hashimoto's thyroiditis (HT) may progress to Graves' disease (GD) and that this phenomenon may be more frequent in the patients with Down syndrome (DS). Aims: To shed light on the relationships between Down syndrome (DS) and metamorphic thyroid autoimmunity. Patients and Methods: We reconstructed the conversion process from HT to GD in 12 DS children. All the data recorded at HT diagnosis and throughout the time interval from entry to GD presentation were retrospectively taken from patients' files, as well as those recorded at GD diagnosis and during the subsequent evolution. From GD diagnosis all patients underwent methimazole treatment, at a dose that was adjusted on the basis of clinical findings and thyroid tests. Results: Time interval between HT and GD was not different in the seven patients who received during that time a L-thyroxine (L-T4) treatment than in those who were not treated. After methimazole onset all patients exhibited a prolonged remission of hyperthyroidism. In 8/12 patients this treatment is still being continued 2-7 years after its initiation. The mean methimazole dosage needed to maintain euthyroidism in these eight patients was 0.12 ± 0.02 mg/kg/day. In the remaining four patients methimazole was withdrawn from 1.9 to 7 years after its initiation and no relapses were recorded 2.0-2.1 years after its withdrawal. These patients developed, 0.1-0.3 years after methimazole withdrawal, a picture of overt hypothyroidism and needed treatment with L-T4, that is now being continued. No patients needed non-pharmacological therapies. Conclusions: 1) DS children might be incline to manifest over time a phenotypic metamorphosis from HT to GD and to subsequently fluctuate from hyperthyroidism to hypothyroidism; 2) in DS GD may have a mild biochemical and clinical course.


2015 - Mi presento, senza tosse– amyco plasma [Articolo su rivista]
Bedetti, Luca; Martignoni, Laura; Tricarico, Antonella; Guerzoni, Maria Elena; Motta, Alice; Bruzzi, Patrizia; Guerra, Azzurra; Paolucci, Paolo; Iughetti, Lorenzo
abstract

I due casi descritti sottolineano come alterazioni a carico del SNC da M. pneumoniae vadano prese in considerazione in bambini con sintomi neurologici in corso di infezioni del tratto alto o basso respiratorio.


2015 - Novel insights on the treatment of hypercholesterolemia [Articolo su rivista]
Iughetti, Lorenzo; Predieri, Barbara; Bruzzi, Patrizia
abstract

The diagnosis of dyslipidemia is increasing both in adulthood and in childhood because of not only the steadily increasing prevalence of obesity but also a rise of medical attention in detecting unfavorable genetic conditions in patients of all ages. Attempts in lifestyle changes are frequently failing and thus the pharmacological treatment of dyslipidemia is spreading in medical practice to reduce cardiovascular risk. In childhood, statins are authorized by 8 years of age. Nevertheless, data on their long-term safety and efficacy are still lacking, especially in ones with high cardiovascular risk and/or primary dyslipidemia such as homozygous familial hypercholesterolemia, considerable as a mainly exclusively pediatric disease. Thus, new pharmacological approaches are needed and have to be evaluated in all categories of patients. In this context, the update and the critical revision of new medications have become a new duty for scientists and clinicians.


2015 - Organization and regional distribution of centers for the management of children and adolescents with diabetes in Italy [Articolo su rivista]
Giorgetti, Chiara; Ferrito, Lucia; Zallocco, Federica; Iannilli, Antonio; Cherubini, Valentino; Study Group for Diabetes of, Ispe; Maghnie, M; Rabbone, I; De Luna, L; Kienberger, B; Gualtieri, A; Zecchino, C; Piccino, E; Ortolani, F; Zucchini, S; Maltoni, G; Pasquino, B; Reinstadler, P; Prandi, E; Zattoni, V; Gallo, F; Morganti, G; Guerraggio, L; Ripoli, C; Frongia, M; Pusceddu, P; Scanu, P; Cardinale, G; Ponzi, G; Tomaselli, L; Rapisarda, V; Citriniti, F; Soprani, T; Tumini, S; Lazzaro, N; Banin, P; Toni, S; Lenzi, L; Mainetti, B; Coccioli, M; D'Annunzio, G; Minuto, N; Montani, E; Maccioni, R; Marongiu, U; Beccaria, L; Bruzzese, M; Mammì, F; Pardi, D; Carrara, M; Lombardo, F; Ventrici, C; Scaramazza, A; Ferrari, M; Bonfanti, R; Rigamonti, A; Iughetti, Lorenzo; Predieri, Barbara; Iafusco, D; Confetto, S; Zanfardino, A; Prisco, F; Francese, A; Cadario, F; Milia, A; Piredda, G; Mereu, L; Soro, M; Correddu, A; Pipia, A; Monciotti, C; Cardella, F; De Berardinis, F; Santoro, G; Chiari, G; Berioli, M; Federico, G; Zanette, G; Marsciani, A; Pedini, A; Patera, I; Schiaffini, R; Bitti, M; Lidano, R; Pietrosanti, S; Delvecchio, M; Trada, M; Marinaro, A; Meloni, G; Galero, A; Fichera, G; Bulciolu, P; Rabbone, I; Ignaccolo, G; Cauvin, V; Franceschi, R; Faleschini, E; Tornese, G; Salvatoni, A; Cardani, R; Maffeis, C; Marigliano, M; Sabbion, A; Arnaldi, C.
abstract

Background - The incidence of type 1 diabetes in childhood is increasing by 3 % per year, placing growing demands on healthcare professionals and medical expenditures. Aim of this study wars to assess the organization of care to children with diabetes in Italy. Methods - During 2012 a structured questionnaire was sent to all of the members of Italian Society of Paediatric Endocrinology and Diabetology (ISPED). Questions examined organizational structure of Centers, personnel dedicated to the care of children with diabetes, number of subjects followed, local legal legislation supporting centres. Results - A total of 68 centers taking care to 15,563 children and adolescents with diabetes under 18 years of age were identified with a prevalence of 1.4 per 1,000 people. A wide variation in the organizational background was also reported. Fourty-four centers were organized as outpatient departments, 17 as simple units, 5 as complex units and 2 as simple departmental structures. Most centers had a multidisciplinary team. Ten out of twenty Italian regions had introduced supportive regional legislation, but it was fully applied only in six of them. Conclusion - Great differences between regions were found in organizational structures, staffing levels and supportive legislation. The national legislation on diabetes was broadly implemented throughout the country regions. Further efforts are needed to improve standards and consistency of pediatric diabetes care in Italy.


2015 - Peculiarities of presentation and evolution over time of Hashimoto's thyroiditis in children and adolescents with Down's syndrome [Articolo su rivista]
Aversa, Tommaso; Salerno, Mariacarolina; Radetti, Giorgio; Faienza, Maria Felicia; Iughetti, Lorenzo; Corrias, Andrea; Predieri, Barbara; Mussa, Alessandro; Mirabelli, Silvestro; De Luca, Filippo; Wasniewska, Malgorzata
abstract

Background: Studies concerning presentation and evolution over time of Hashimoto’s thyroiditis (HT) in children with Down’s syndrome (DS) are few, are based on limited study populations and do not include control HT groups without DS. The aim of this multicenter study was to shed further light on the relationships between DS and HT in childhood. DESIGN: In this retrospective study we compared thyroid function patterns at HT presentation in 2 groups of children with (group A) or without DS (group B), including 146 and 553 cases, respectively. All group A patients were subsequently re-examined after a median interval of 5.1 years in order to prospectively re-evaluate the evolution over time of thyroid function patterns in DS. Results: In group A, female predominance, age at HT diagnosis and rates of familiarity for thyroid diseases were significantly lower than in group B, whilst the association with non-thyroidal autoimmune diseases was more frequent. The hormonal patterns that were most frequently found in the 2 groups were, respectively, subclinical hypothyroidism (in group A) and euthyroidism (in group B). Thyroid dysfunctions were, overall, more frequent in group A (86.3 vs 45.7%, p&lt;0.001). At re-evaluation, DS children exhibited further deterioration of thyroid function with some cases switching towards Graves’ disease (GD). Conclusions: HT in DS children: a) presents earlier, is not associated with female predominance and is more frequently associated with other autoimmune diseases; b) presents only very infrequently with a euthyroid hormonal profile; c) in a limited rate of cases switches with time to GD.


2015 - Pediatric cholesterol screening in Italy: The SPIF project [Abstract in Rivista]
Iughetti, Lorenzo
abstract


2015 - Precocious pubertal development: a challenge for pediatric endocrinologists [Articolo su rivista]
Iughetti, Lorenzo; Lucaccioni, Laura
abstract

Precocious puberty is one of the most common conditions encountered in the pediatric endocrinology clinic and can be defined as the appearance of secondary sexual characteristics in girls under 8 years and boys under 9 years of age. The timing of pubertal onset has received increasing attention because of a reported gradual decline in age at menarche in most populations. Proposed mechanisms for these changes include: an improvement in socioeconomic conditions with consequent increased nutritional status and a rise in a number of environmental pollutants. The challenges for pediatric endocrinologists are increasing: what are the mechanisms of precocious puberty in modern society? Should our diagnostic criteria be changed? When to treat? What are the consequences of treatment? Little is known of the short and long term consequences of GnRH-analog treatment, especially in terms of psychological consequences for children and their families.


2015 - Quando l’acqua cheta… rode i timpani [When the still waters... gnaws the eardrums] [Articolo su rivista]
Predieri, Flavia; Brocchi, Silvia; Filippini, Beatrice; Vergine, Gianluca; Viola, Laura; Marsciani, Alberto; Ancora, Gina; Iughetti, Lorenzo
abstract

L’otomastoidite va tenuta in considerazione nella diagnosi differenziale della paralisi del nervo facciale, che ne costituisce una rara complicanza, la cui incidenza stimata è dello 0,005% e la cui prognosi è eccellente con atteggiamento terapeutico conservativo.


2015 - SINDROME UREMICO-EMOLITICA ATIPICA IN LATTANTE EX-PRETERMINE [Abstract in Rivista]
Tricarico, Antonella; Lusetti, Elisa; Iughetti, Lorenzo
abstract

La SEUa, di cui esistono diverse varianti genetiche, conduce ad exitus dal 2-10% dei casi ed in un terzo progredisce fino all’insufficienza renale.


2015 - Stroke cerebellare e dissezione dell’arteria vertebrale in una adolescente [Cerebellar stroke and vertebral artery dissection in an adolescent] [Articolo su rivista]
E., Manzotti; V., Bianco; B., Filippini; G., Vergine; Iughetti, Lorenzo; A., Marsciani
abstract

A 13-year-old girl presented with progressive frontal he-adache, dizziness, vomiting and hypotonia, with heat sen-sation and hyperidrosis. She referred a “contraction” of the neck some days before, while she was doing gymna-stics. The only physical sign was coarse tremor of the left lower limb to the test Mingazzini. Laboratory and radio-logic exams were normal, but cerebral MRI and angio-MRI put in evidence some ischemic spots in the left cere-bellar emisphere and cerebellar vermis; they originated from a dissection of the vertebral artery, evidenced by an angio-MRI of the supra-aortic arteries. After 10 months of low dose acetylsalicylic acid therapy, symptoms resol-ved almost completely, with no new ischemic events. The cerebellar lesions were resolving, as well as the small pseudoaneurysm at the level of dissection. Cerebellar stroke is rare in children, the spontaneous dissection of the vertebral arteries can be one of the possible etiolo-gies, even with no history of cervical trauma.


2015 - The impact of the Italian guidelines on antibiotic prescription practices for acute otitis media in a paediatric emergency setting [Articolo su rivista]
Palma, Silvia; Rosafio, Cristiano; DEL GIOVANE, Cinzia; Patianna, VIVIANA DORA; Lucaccioni, Laura; Genovese, Elisabetta; Bertolani, Paolo; Iughetti, Lorenzo
abstract

Acute otitis media (AOM) is one of the most common childhood infectious diseases. The recent Italian Pediatric Guidelines for the treatment of AOM constitutes a step forward in the management of children with uncomplicated AOM. The aim of this study was to evaluate antibiotic prescription patterns for AOM in a Pediatric Emergency Department (PED) after those guidelines were introduced and to assess the relationship between implementation of the "watchful waiting" strategy and the incidence of acute mastoiditis in the PED.


2015 - Thyroid function in Down syndrome [Articolo su rivista]
Iughetti, Lorenzo; Lucaccioni, Laura; Fugetto, Francesco; Mason, Avril; Predieri, Barbara
abstract

Down syndrome is the most commonly encountered human chromosomal disorder. Down syndrome is associated with thyroid dysfunction including: hypothyroidism, both congenital and acquired, and hyperthyroidism. A genetic predisposition and a propensity to acquire autoimmune disorders seem to be possible factors, though their causal relation remains unclear. The aim of the review is to describe what is currently known about the association between Down syndrome and thyroid dysfunction.


2015 - Un dolore che sveglia di notte [Pain that wakes you up at night...] [Articolo su rivista]
Mazzoni, Silvia; Roncuzzi, Francesca; Pietrangiolillo, Zaira; Montanari, Lisa; Martignoni, Laura; Bedetti, Luca; Malmusi, Giovanni; Motta, Alice; Mandese, Valentina; Cantatore, Sante Lucio; Bruzzi, Patrizia; Cellini, Monica; Cano, Carmen; Paolucci, Paolo; Iughetti, Lorenzo
abstract

Il sarcoma di Ewing (SE) è un tumore osseo maligno che insorge preferenzialmente a 10-20 anni, a livello di pelvi, diafisi omerale e femorale. Il 25% dei pazienti, alla diagnosi, ha già metastasi polmonari e ossee. Tra le manifestazioni tipiche: dolore, limitazione funzionale, rialzo febbrile, malessere, aumento delle LDH nel 30% dei casi.


2015 - UNA STRANA ENCEFALITE [Abstract in Rivista]
Lusetti, Elisa; Tricarico, Antonella; Iughetti, Lorenzo
abstract

L’encefalite da anticorpi antiNMDAR è una forma autoimmune presente a qualunque età: in adolescenza e in età adulta è spesso una condizione paraneoplastica (teratoma ovarico), dato raro in età pediatrica. L’esordio può essere anticipato da prodromi aspecifici (febbre, vomito, astenia, malessere), ed è caratterizzato da sintomi psichiatrici, come alterazione del tono dell’umore, ansia, agitazione, pensieri paranoidi, disinibizione, allucinazioni. In associazione compaiono disturbi del movimento (stereotipie, discinesie orofacciali, movimenti ritmici degli arti), che possono mimare le crisi epilettiche, deficit di memoria, alterazioni del linguaggio, insonnia, disturbi autonomici.


2014 - A Novel Mutation in the TITF1 Gene in a Child with Benign Hereditary Chorea [Abstract in Rivista]
Patianna, VIVIANA DORA; Predieri, Barbara; L., Garavelli; C., Fusco; S. F., Madeo; Bruzzi, Patrizia; Iughetti, Lorenzo
abstract

Our patient presented a ‘de novo mutation’ and the choreic jerks were subtle and were not the dominant clinical feature.


2014 - Adherence to Growth Hormone therapy: a practical approach. [Articolo su rivista]
Bozzola, M; Pagani, S; Iughetti, Lorenzo; Maffeis, C; Bozzola, E; Meazza, C.
abstract

Background: Early detection of suspected poor adherence to growth hormone (GH) therapy is crucial to achieve normal final height in GH-deficient (GHD) patients. Patients: 106 children (73 M, 33 F) with a median age of 10.47 ± 3.48 years (mean ± standard deviation score (SDS)) exhibited short stature (-1.76 ± 0.64 SDS) and a delayed bone age (8.68 ± 3.42 years). Severe GHD was found in 28, while partial GHD was seen in 78 cases, with low IGF-I values. Recombinant human GH was administered by daily subcutaneous injection at a dosage of 21 µg/kg in prepubertal and 25 µg/kg in pubertal patients. Results: Poor adherence was suspected in a number of patients, but clearly demonstrated in only 4 cases with persistent reduced height velocity in spite of a corrected therapeutic regimen. These patients admitted incomplete adherence to GH injections and clinical and anthropometric measurements revealed their poor response to therapy. Conclusions: To efficaciously improve adherence in GHD patients, it is mandatory to regularly interview patients; a non-aggressive approach might be utilized to ensure effective communication with patients and their parents.


2014 - Combined Therapy with Insulin and Growth Hormone in 17 Patients with Type-1 Diabetes and Growth Disorders. [Articolo su rivista]
Zucchini, S; Iafusco, D; Vannelli, S; Rabbone, I; Salzano, G; Pozzobon, G; Maghnie, M; Cherubini, V; Bizzarri, C; Bonfanti, R; D'Annunzio, G; Lenzi, L; Maggio, Mc; Marigliano, M; Scaramuzza, A; Tumini, S; Iughetti, Lorenzo
abstract

Combined growth hormone (GH) and insulin therapy is rarely prescribed by pediatric endocrinologists. We investigated the attitude of Italian physicians to prescribing that therapy in the case of short stature and type-1 diabetes (T1DM). Methods: A questionnaire was sent and if a patient was identified, data on growth and diabetes management were collected. Results: Data from 42 centers (84%) were obtained. Of these, 29 centers reported that the use of combined therapy was usually avoided. A total of 17 patients were treated in 13 centers (GH was started before T1DM onset in 9 patients and after the onset of T1DM in 8). Height SDS patterns during GH therapy in the 11 patients affected by GH deficiency ranged from -0.3 to +3.1 SDS. In the 8 diabetic patients in whom GH was added subsequently, mean insulin dose increased during the first 6 months of therapy from 0.7 ± 0.2 to 1.0 ± 0.2 U/kg (p = 0.004). HbA1c was unchanged during the first 6 months of combined therapy. Conclusions: Most Italian physicians do not consider prescribing the combined GH-insulin therapy in diabetic children with growth problems. However, the results of the 17 patients identified would confirm that the combined therapy was feasible and only caused mild insulin resistance. GH therapy was effective in promoting growth in most patients and did not affect diabetes metabolic control


2014 - Diagnosis and management of acute mastoiditis in a cohort of Italian children. [Articolo su rivista]
Marchisio1, P1; Bianchini2, S2; Villani3, A3; Verri4, G4; Bernardi5, F5; Porta6, A6; Biban7, P7; Caimmi, S.; Iughetti, Lorenzo; Krzysztofiak10, A10; Garazzino11, S11; Romanin12, B12; Salvini13, F13; Lancella14, L14; Landini 15, S15; Galeone16, C16; Esposito17, S17; Principi18, N. 1. 8.
abstract

The Italian Society for Pediatric Infectious Diseases created a registry to determine the management of pediatric acute mastoiditis (AM) in Italy. A cross-sectional survey of paediatricians was conducted to evaluate hospitalization due to AM in Italian pediatric wards between 1 January 2002, and 31 December 2013. A total of 913 children (561 males, 61.4%) were included in this study. The annual number of AM cases significantly increased during the study period (30 in 2002 and 98 in 2013) but only among older children (≥ 4 years old; p = 0.02). AM complications occurred in 69 (7.6%) of the children and sequelae were observed in 13 (1.4%) patients. The annual number of pediatric AM cases admitted to Italian pediatric wards increased in the past few years; this increase was strictly age-related. The risk of severe AM complications appeared relatively low, and most AM cases could be treated conservatively


2014 - Ecthyma gangrenosum neonatale: quando la chirurgia non è possibile... [Relazione in Atti di Convegno]
Ricarico, A; Bianco, V; Vellani, G; Bianchini, Ma; Durante, V; Di Pancrazio, L; Ceccarelli, Pl; Iughetti, Lorenzo; Cacciari, Alfredo; Ferrari, Fabrizio
abstract

Il riconoscimento precoce di una lesione cutanea caratteristica come l'Ecthyma gangrenosum neonatale (EG) in un neonato critico, deve suggerire il rischio di una potenziale sepsi da Pseudomonas Aeruginosa (PA).


2014 - Epidemiologia della chetoacidosi diabetica in Italia [Articolo su rivista]
Cherubini, Valentino; Gesuita, R.; Sternardi, S.; Ferrito, L.; Lenzi, L.; Iannilli, A.; Piccini, B.; Skrami, E.; Nicolucci, A.; Pintaudi, B.; Toni, S.; Lera, R.; De Luna, L.; Kienberger, B.; Ferrito, L.; Gualtieri, A.; Zecchino, C.; Piccino, E.; Ortolani, F.; Zucchini, S.; Maltoni, G.; Pasquino, B.; Reinstadler, P.; Prandi, E.; Zattoni, V.; Gallo, F.; Morganti, G.; Guerraggio, L.; Ripoli, C.; Frongia, M.; Pusceddu, P.; La Loggia, A.; Scanu, P.; Cardinale, G.; Ponzi, G.; Tomaselli, L. G.; Rapisarda, V.; Citriniti, F.; Soprani, T.; Tumini, S.; Lazzaro, N.; De Donno, V.; Banin, P.; Toni, S.; Lenzi, L.; Mainetti, B.; Coccioli, M. S.; D'Annunzio, G.; Minuto, N.; Montani, E.; Maccioni, R.; Marongiu, U.; Beccaria, L.; Bruzzese, M.; Mammì, F.; Pardi, D.; Lombardo, F.; Ventrici, C.; Scaramazza, A.; Ferrari, M.; Bonfanti, R.; Rigamonti, A.; Iughetti, Lorenzo; Predieri, Barbara; Iafusco, D.; Confetto, S.; Zanfardino, A.; Prisco, F.; Franzese, A.; De Nitto, E.; Cadario, F.; Milia, A.; Piredda, G.; Mereu, L.; Soro, M.; Correddu, A.; Pipia, A.; Monciotti, C.; Cardella, F.; De Berardinis, F.; Santoro, G.; Chiari, G.; Berioli, M. G.; Federico, G.; Zanette, G.; Marsciani, A.; Pedini, A.; Patera, I. P.; Schiaffini, R.; Bitti, M.; Lidano, R.; Pietrosanti, S.; Delvecchio, M.; Trada, M.; Marinaro, A.; Meloni, G.; Galero, A.; Fichera, G.; Bulciolu, P.; Rabbone, I.; Ignaccolo, G.; Cauvin, V.; Franceschi, R.; Faleschini, E.; Tornese, G.; Salvatoni, A.; Cardani, R.; Maffeis, C.; Marigliano, M.; Sabbion, A.; Arnaldi, C.
abstract

Ketoacidosis is a potentially life-threatening complication in patients with type 1 diabetes mellitus (T1DM), particularly children. If diabetic ketoacidosis (DKA) is diagnosed late, the child risks cerebral edema, permanent neurological damage or even death. There have been only few studies of DKA in Italy. From January-May 2014 a nation-wide observational, retrospective study of DKA at diabetes onset was done by the Pediatric Diabetology Study Group (PDSG) of the Italian Society of Pediatric Endocrinology and Diabetes (ISPED), involving 76 Italian centers. DKA was defined using ISPAD criteria; 7457 new cases of T1DM were recruited from mainland Italy and the island of Sicily and 770 from Sardinia, in the period 2004-2013. On the mainland and in Sicily, DKA at diabetes onset was about 32.9% (95% CI 31.8-34.0%), and there was 6.6% (95% CI 6.02-7.20%) of the severe form. Mild and severe DKA risk was significantly higher in children aged 0-4 years; no significant temporal trend was found in the study period. Patients living in Sardinia or having a firstdegree relative with T1DM were at significantly lower risk of DKA at diabetes onset. In the ten-year study period three children died of DKA at onset and four suffered permanent neurological lesions. From November 2011-April 2012 the PDSG conducted a retrospective study based on a sample of 2025 patients with T1DM, aged 0-18 years, involving 29 national centers for pediatric diabetes. The incidence of DKA was 2.4% (IC 95% 1.8-3.1), with children older than ten years at significantly higher risk, probably due to shortages of insulin. Multiple analysis showed a higher risk of DKA in those using a rapid-acting insulin analog and in those with high HbA1c. Young mothers and low levels of education were also associated with DKA. In conclusion, although a wide network of specialized home pediatricians and pediatric diabetes centers is spread across the country, the incidence of DKA at diabetes onset is still high. Further social and health-system efforts are needed to boost awareness of this risk and to reduce damages and costs related to the complication.


2014 - Final Height and BMI in English and Italian Adult Survivors of Childhood Acute Lymphoblastic Leukemia Treated without Cranial Radiotherapy [Abstract in Rivista]
Bruzzi, Patrizia; A., Albanese; S., Nussey; Predieri, Barbara; Iughetti, Lorenzo; A., Leiper
abstract

CT alone minimizes the loss in FH SDS together with the increase in BMI SDS in adult survivors of childhood. Females seem more susceptible to CT effects, especially when exposed to high dose MTX.


2014 - Final height and body mass index in adult survivors of childhood acute lymphoblastic leukemia treated without cranial radiotherapy: a retrospective longitudinal multicenter Italian study. [Articolo su rivista]
Bruzzi, Patrizia; Predieri, Barbara; Corrias, A; Marsciani, A; Street, Me; Rossidivita, A; Paolucci, Paolo; Iughetti, Lorenzo
abstract

BACKGROUND: Young adult survivors of childhood acute lymphoblastic leukemia (ALL) treated with protocols including cranial radiotherapy demonstrate a persistent weight gain and reduced final height. Published reports on the effects on growth of different oncologic therapies are conflicting and difficult to interpret because they combined children treated with both cranial irradiation and multi-agent chemotherapy. Our study investigated the effect of chemotherapy alone on body mass index (BMI) and on growth at the achievement of final height in a homogeneous cohort of Italian childhood ALL survivors. METHODS: We retrospectively studied 162 Caucasian patients treated on the Italian Association of Pediatric Hematology and Oncology protocols without radiotherapy between 1989 and 2000 at five Italian centers with 107 inclusions (58 males). Height- and BMI-standard deviation score (SDS) were collected at diagnosis of ALL, at the end of treatment and at the achievement of final height. Changes in height SDS and BMI SDS with time were analyzed using dependent sample Student's t-test. RESULTS: A significant reduction of height-SDS was documented during treatment in both genders. This reduction of height-SDS was not followed by an appropriate catch-up growth, despite the achievement of a mean final height within the normal range. At diagnosis females showed a lower mean BMI-SDS than males. During treatment, in the whole population, BMI-SDS increased significantly. After it, while males lost BMI-SDS, females showed its persistent increase. CONCLUSIONS: Survivors of childhood ALL generally seemed to achieve a normal final height with a BMI within the normal range. These parameters appeared to be only minimally affected by chemotherapy. Nevertheless, height catch-up growth was not completed after chemotherapy in both genders and all patients experienced an increase of BMI-SDS during chemotherapy that only females seemed to conserve until the achievement of final height.


2014 - Geographic variation in the frequency of abdominal adiposity and metabolic syndrome in Italian adolescents with type 1 diabetes. [Articolo su rivista]
Valerio, G1; Maffeis, C; Zucchini, S; Lombardo, F; Toni, S; Rabbone, I; Federico, G; Scaramuzza, A; Franzese, A; Cherubini, V; Zedda, Ma; Calcaterra, V; Lera, R; Cardinale, G; Bruzzese, M; Iughetti, Lorenzo; Gallo, F; De Donno, V; De Berardinis, F; Iafusco, D.
abstract

Geographic variation in the frequency of abdominal adiposity and metabolic syndrome in Italian adolescents with type 1 diabetes were described


2014 - GH Stimulated Levels in Prader–Willi Syndrome During the Transition Period between Childhood and Adulthood [Abstract in Rivista]
G., Grugni; A., Corrias; S., Di Candia; D., Fintinid; L., Gargantini; Iughetti, Lorenzo; L., Ragusa; A., Salvatoni; A., Sartorio; S., Bocchini; M., Delvecchioi; G., Chiumelloc; A., Crino
abstract

The objective of this study was to investigate the GH response to combined GHRHCarginine administration in a large group of PWS patients during the transition period


2014 - Health consequences of obesity in children and adolescents. [Articolo su rivista]
Valerio, G; Licenziati, Mr; Manco, M; Ambruzzi, Am; Bacchini, D; Baraldi, E; Bona, G; Bruzzi, Patrizia; Cerutti, F; Corciulo, N; Crinò, A; Franzese, A; Grugni, G; Iughetti, Lorenzo; Lenta, S; Maffeis, C; Marzuillo, P; Miraglia Del Giudice, E; Morandi, A; Morino, G; Moro, B; Perrone, L; Prodam, F; Ricotti, R; Santamaria, F; Zito, E; Tanas, R.
abstract

Obesity in childhood is associated with the presence of complications that can undermine health immediately or in the long term. Several conditions, such as pulmonary or orthopedic complications are strictly associated with the severity of overweight, since they are directly associated to the mechanic stress of fat tissue on the airways or on the bones. Other conditions, such as metabolic or liver complications, although increasing with the extent of overweight, are associated with insulin resistance, which can be modulated by different other factors (ethnicity, genetics, fat distribution) and can occur in overweight children as well. No less important are psychological correlates, such as depression and stigma, which can seriously affect the health related quality of life. Pediatric services for the care of childhood obesity need to be able to screen overweight and obese children for the presence of physical and psychological complications, which can be still reversed by weight loss. This article provides pediatricians a comprehensive update on the main complications in obese children and adolescents and their treatment.


2014 - Hydrops fetalis in a preterm newborn heterozygous for the c.4A>G SHOC2 mutation. [Articolo su rivista]
Gargano, G; Guidotti, I; Balestri, Eleonora; Vagnarelli, F; Rosato, S; Comitini, G; Wischmeijer, A; LA SALA, Giovanni Battista; Iughetti, Lorenzo; Cordeddu, V; Rossi, C; Tartaglia, M; Garavelli, L.
abstract

Fetal hydrops is a condition resulting from interstitial fluid accumulation in fetal compartments secondary to increased capillary permeability and characterized by high rates of perinatal mortality and morbidity. Clinical features include skin edema, hydrothorax, pericardial effusion, ascites with or without polyhydramnios, and placental edema. While it may occur as associated feature in multiple disorders, it has been documented to recur in Noonan syndrome, the most common disorder among RASopathies, but also in cardiofaciocutaneous and Costello syndromes. Here, we report on the occurrence of severe hydrops in a newborn heterozygous for the invariant c.4A>G missense change in SHOC2 which underlies Noonan-like syndrome with loose anagen hair, documenting that it represents a clinically relevant complication in this condition, shared by RASopathies.


2014 - I disturbi del sonno: il Progetto “Ci piace sognare” [Articolo su rivista]
Brambilla, P; Barberi, S; Bernasconi, S; Bona, G; Brusoni, G; Buongiovanni, C; Carotenuto, M; Chiappini, E; Di Mauro, G; Ghiglioni, D; Gnecchi, M; Giussani, M; Iughetti, Lorenzo; Maffeis, C; Miraglia Del Giudice, E; Pasinato, A; Picca, M; Privitera, F; Sticco, M; Tamassia, G; Venturelli, L; Verduci, E; Villella, A.
abstract

N.A.


2014 - In Vitro derivation of insulin-producing cells from 3D spheroids of human amniotic epithelial cells [Abstract in Rivista]
Okere, B; Alviano, F; Patianna, V; Costa, R; Predieri, Barbara; Quaglino, Daniela; Ricci, F; Dominici, Massimo; Paolucci, P; Bonsi, L; Iughetti, Lorenzo
abstract

Objective: Regenerative medicine and stem cell therapy represent a promising tool for the treatment of non-curable human diseases such as type 1 diabetes. Human amniotic epithelial cells (hAECs) from term placenta have attracted growing interest for their immunological properties, plasticity and availability which make them a promising tool for stem cell-based therapeutic applications. The aim of our study was to culture hAECs in serum-free condition preserving their phenotypic and genetic traits, evaluating their pancreatic differentiative potential in a 3D fashion. Methods: hAECs were isolated and cultured in standard serum-rich medium and serum-free optimized media. Flow Cytometry analysis was performed to evaluate stemness and specific epithelial cells markers. qPCR assessed stem cell and proliferation markers. We established a 3D culture procedure on basement membrane extracts to obtain spheroids mimicking the in vivo morphology and spatial organization of pancreatic islets. Results: The serum free protocol we developed proved to maintain hAECs stemness characteristics and confirmed their immunomodulatory activity on PHA stimulated PBMCs as revealed by proliferation assays. Immunofluorescence revealed the presence of pancreatic endocrine hormones and transmission electron microscopy (TEM) analysis showed a clear membrane-associated organization of secretory granules, consistent with beta cell ultrastructure in vivo. Conclusion: We accordingly propose the outcomes of this study as a novel contribution to the development of a future cell replacement therapy for type 1 diabetes.


2014 - Increasing burden, younger age at onset and worst metabolic control in migrant than in Italian children with type 1 diabetes: an emerging problem in pediatric clinics. [Articolo su rivista]
Cadario, F1; Cerutti, F; Savastio, S; Rabbone, I; Tumini, S; Bruno, G; Lera, R; Cherubini, V; Bechaz, M; Zucchini, S; Prandi, E; Zattoni, V; Coccioli, S; Frongia, A; La Loggia, A; Lo Presti, D; Citrini, F; Suprani, T; Dedonno, V; Vergerio, A; Banin, P; Toni, S; Piccini, B; Barni, F; Pescamona, M; Cardinale, G; Lombardo, F; Bonfanti, R; Scaramuzza, A; Iughetti, Lorenzo; Franzese, A; Iafusco, D; Guercio Nuzio, S; Abiuso, C; Monciotti, C; Cardella, F; Vanelli, M; Chiari, G; Calcaterra, V; De Giorgi, G; Zanette, G; Marsciani, A; Patera, P; Manca Bitti, M; Delvecchio, M; Trada, M; Aimar, A; Gaiero, A; Tinti, D; Fontana, F; Guerraggio, L; Cauvin, V; Gargantini, L; Salvatoni, A; Trivellin, V; Maffeis, C; Marigliano, M; Arnaldi, C.
abstract

To assess burden and clinical features of type 1 diabetes in migrant with respect to Italian children. Prevalent children with type 1 diabetes were identified through a multicenter study, including 46 pediatric outpatients diabetic clinics. A nested case-control study was also performed, comparing features at diabetes onset and after 1 year of insulin treatment in 84 migrants and 75 Italian children with onset in 2011, matched for age and sex. Out of 7,812 children cared for by pediatric diabetologists, 761 (10%) were migrant and 548 of them were born in Italy. Age at diagnosis was lower in migrants born in Italy (5.1 years, interquartile range (IQR) 2.2-7.7) than in those born in their original countries (7.8 years, IQR 5.3-10.3) and in Italians (9.8 years, IQR 5.9-13.0, p < 0.001). At diabetes onset, migrants had lower frequencies of positivities of markers of β-cell autoimmunity (96 vs. 99.5%, p < 0.01), higher values of weight loss (11 vs. 7%, p < 0.01), HbA1c (70 vs. 58 mmol/mol, p < 0.001), and insulin requirement (0.70 ± 0.03 vs. 0.63 ± 0.10 UI/kg/die, p = 0.05) and lower levels of 25-OH vitamin D3 (15.0 ± 2.8 vs. 20.8 ± 1.3, p = 0.03). Moreover, they experienced higher frequencies of hospitalizations during the first year of disease (19.2 vs. 2.7%, p < 0.001). Burden of type 1 diabetes in migrant children is increasing in Italy, with younger age at onset and different clinical features than in Italian children. Higher hospitalization rates and poorer glycemic control over the first year underline that approach to diabetes care in migrants needs to be improved.


2014 - Longitudinal evaluation of endothelial function in children and adolescents with type 1 diabetes mellitus: a long term follow up study. [Articolo su rivista]
Bruzzi, Patrizia; Predieri, Barbara; Patianna, VIVIANA DORA; Salvini, Annamaria; Rossi, Rosario; Modena, Maria Grazia; Iughetti, Lorenzo
abstract

BACKGROUND: Type 1 diabetes (T1DM) predisposes to cardiovascular disease increasing the risk to develop atherosclerosis. In pediatric population the cardiovascular risk may be evaluated examining endothelial function by a noninvasive ultrasound technique, namely flow-mediated dilation (FMD) of the brachial artery. The aims of this study were the longitudinal evaluation of the potential change in the endothelium-dependent vasomotor function in children and adolescents with T1DM and the identification of clinical and laboratory data correlated to modifications. METHODS: We studied 39 T1DM patients (20 girls and 19 boys; aged 11.2 ± 3.72 years). FMD and blood samples were obtained from all patients at baseline (time 0) and after a follow-up of at least 1 year (time 1). FMD was also evaluated in 45 healthy controls (22 boys, 23 girls) aged 10.2 ± 3.05 years. RESULTS: At time 0, 43.6% T1DM patients presented an impaired FMD. FMD at time 1 revealed a dramatic impairment of endothelial function: altered FMD values were shown in 61.5% of patients and it got worse in 74.3% of them. Longitudinally males had a greater impairment of FMD than females. At baseline multivariate analysis identified only gender as significant predictor of FMD (β = 0.470, p = 0.029). CONCLUSIONS: Because endothelial dysfunction appears earlier in diabetic children, they are at higher risk to develop atherosclerosis. Our results suggest the usefulness of FMD as a tool to stratify pediatric T1DM patients according to their cardiovascular risk and to follow up them longitudinally.


2014 - Metabolic Assessment in Children with GH Deficiency Before, During, and After Human GH Replacement Therapy [Abstract in Rivista]
Predieri, Barbara; Mazzoni, Silvia; V., Paraluppi; Patianna, VIVIANA DORA; Lucaccioni, Laura; S., Madeo; Bruzzi, Patrizia; Iughetti, Lorenzo
abstract

To assess changes of lipid profile, insulin-resistance indexes, and CVD risk in children and adolescents with GHD before, during, and after rhGH therapy


2014 - Multiple sulfatase deficiency with neonatal manifestation. [Articolo su rivista]
Garavelli, L; Santoro, L; Iori, A; Gargano, G; Braibanti, S; Pedori, S; Melli, N; Frattini, D; Zampini, L; Galeazzi, T; Padella, L; Pepe, S; Wischmeijer, A; Rosato, S; Ivanovski, I; Iughetti, Lorenzo; Gelmini, C; Bernasconi, S; Superti Furga, A; Ballabio, A; Gabrielli, O.
abstract

Multiple Sulfatase Deficiency (MSD; OMIM 272200) is a rare autosomal recessive inborn error of metabolism caused by mutations in the sulfatase modifying factor 1 gene, encoding the formyglycine-generating enzyme (FGE), and resulting in tissue accumulation of sulfatides, sulphated glycosaminoglycans, sphingolipids and steroid sulfates. Less than 50 cases have been published so far. We report a new case of MSD presenting in the newborn period with hypotonia, apnoea, cyanosis and rolling eyes, hepato-splenomegaly and deafness. This patient was compound heterozygous for two so far undescribed SUMF1 mutations (c.191C¿>¿A; p.S64X and c.818A¿>¿G; p.D273G).


2014 - Non la solita ipotonia [Abstract in Rivista]
Patianna, VIVIANA DORA; Predieri, Barbara; Iughetti, Lorenzo
abstract

N.A.


2014 - Nutrizione e diabete: punti fermi e spunti di riflessione [Articolo su rivista]
Tommasi, M.; Bruzzi, Patrizia; Iughetti, Lorenzo; Maffeis, C.
abstract

Il ruolo della dieta nella gestione del diabete e del suo autocontrollo è fondamentale, si tratta a tutti gli effetti di una terapia. Si parla infatti di ‘dietoterapia’ o di Medical Nutrition Therapy come la definisce l’American Diabetes Association (ADA). Fare dell’alimentazione una dietoterapia significa modificare le abitudini alimentari, adottando scelte adeguate dei nutrienti in termini quali/quantitativi, integrandole con cambiamenti dello stile di vita e promozione dell’attività fisica. Gli obiettivi e le raccomandazioni nutrizionali sono in larga parte condivisibili tra la popolazione pediatrica generale e i bambini/adolescenti affetti da diabete. Acquisire infatti sane abitudini alimentari permette di: 1. ottenere una crescita adeguata, raggiungere e mantenere nel tempo una condizione di normopeso e una composizione corporea ottimale; 2. prevenire le complicanze a lungo termine legate a squilibri nutrizionali (ipertensione, dislipidemia, anemia,..); 3. prevenire i disturbi del comportamento alimentare e nello specifico per i soggetti con diabete 4. favorire un buon controllo glicemico ed evitare il più possibile ipoglicemie e/o iperglicemie


2014 - Paraplegia by spinal cord compression as the initial manifestation of Hodgkin's disease: a case report. [Articolo su rivista]
Baroni, L; Fornaciari, S; Predieri, Barbara; Bergonzini, P; Guerra, A; Paolucci, P; Iughetti, Lorenzo
abstract

The 90% of Hodgkin's disease (HD) cases are originated by lymphnodes whereas 10% by extranodal regions as epidural space. Neurologic complications of HD can be classified as directly resulting from the disease or indirectly originated from the disease or from its treatment. Patients very rarely present with spinal cord compression (SCC) due to epidural HD. Few cases of HD with such presentation have been reported in the literature. Primary spinal extradural HD with no further organ involvement is extremely rare. We report a case of a child with SCC as initial and unique presentation of HD.


2014 - Performance of interferon-γ Release Assay for the Diagnosis of Active or Latent Tuberculosis in Children in the First 2 Years of Age [Articolo su rivista]
Silvia, Garazzino; Luisa, Galli; Elena, Chiappini; Michele, Pinon; Bergamini, Barbara Maria; Salvatore, Cazzato; Paola Dal, Monte; Icilio, Dodi; Laura, Lancella; Susanna, Esposito; Iughetti, Lorenzo; Carlotta, Montagnani; Maurizio De, Martino; Pier Angelo, Tovo
abstract

Background: The diagnosis of latent or active tuberculosis in children is often challenging. Recently, interferon-γ release assays have been licensed, but their diagnostic accuracy in young children remains questionable as frequent false-negative or indeterminate results have been reported. Methods: We performed a multicenter, retrospective study in children aged 0–24 months who were tested at least once with QuantiFERON-TB Goldin-tube (QTF-IT) ± tuberculin skin test (TST), to analyze its use and performance in clinical practice. Results: Eight-hundred and twenty-three children (449 males, median age 13.5 months) were enrolled. QTF-IT sensitivity and specificity for active tuberculosis were 92.4% and 98.6%, respectively. Indeterminate tests (4.2 %) were not related to age (P = 0.838) or gender (P = 0.223); 32 children (91.4 %) with an indeterminate QTF-IT ultimately resulted uninfected. In the 616 subjects with valid paired results of QTF-IT and TST, sensitivity and specificity were comparable (91.1% vs. 85.1% and 98.1% vs. 97.9%, respectively). Diagnostic concordance between tests was higher in Bacillus Calmétte-Guerin nonvaccinated children (κ = 0.802). A high rate of discordant tests was observed in latent infections. Conclusions: QTF-IT showed good sensitivity and specificity, and a low rate of indeterminate results in the first 2 years of life, supporting its use at this age. However, considering costs and the similar performance between QTFIT and TST, it is reasonable to suggest the latter as first-line testing in young children. The complementary use of TST and interferon-γ release assays may be considered in selected cases to improve the accuracy of testing.


2014 - Porfiria acuta intermittente: un caso "eccezionale" [Articolo su rivista]
Rosafio, Cristiano; P., Bergonzini; S., Marchini; S., Leoni; C., Fusco; Colli, Serena; Pietrangelo, Antonello; Paolucci, Paolo; Ventura, Paolo; Iughetti, Lorenzo
abstract

Le porfirie, disordini metabolici ereditari ed eterogenei, comprendono 8 quadri clinici causati da mutazioni enzimatiche nella catena biosintetica dell’eme che esitano in un accumulo di precursori tossici e patogenetici. Si distinguono porfirie acute e porfirie cutanee. Le prime, tra le quali la più comune è la porfiria acuta intermittente (AIP), si manifestano con crisi neuroviscerali e a carico del SNP, anche letali, descritte in letteratura quasi esclusivamente in soggetti puberi.


2014 - Recombinant Human GH Therapy Allows to Reach a Normal Final Adult Height in Coeliac Children with GH Deficiency due to Hypophysistis [Abstract in Rivista]
Iughetti, Lorenzo; Lucaccioni, Laura; Bruzzi, Patrizia; A. R., Di Biase; A. M., De Bellis; Predieri, Barbara
abstract

In patients with CD and GHD the association of GFD and rhGH treatment seems to allow an adequate catch-up growth and the achievement of height within target height and presence of LYH seems not to influence the efficacy of the treatment.


2014 - Recommendations for self-monitoring in pediatric diabetes: a consensus statement by the ISPED. [Articolo su rivista]
Scaramuzza, A1; Cherubini, V; Tumini, S; Bonfanti, R; Buono, P; Cardella, F; D'Annunzio, G; Frongia, Ap; Lombardo, F; Monciotti, Ac; Rabbone, I; Schiaffini, R; Toni, S; Zucchini, S; Frontino, G; Iafusco, D; Arnaldi, C; Banin, P; Barbetti, F; Beccaria, L; Benelli, M; Berardi, R; Biagioni, M; Bianchi, G; Bizzarri, C; Blasetti, A; Bobbio, A; Boccato, S; Bonfanti, R; Bontempi, F; Bruzzese, M; Buono, P; Cadario, F; Calcaterra, V; Cannatà, A; Cappa, M; Cardani, R; Cardella, F; Cardinale, Gm; Carloni, I; Castaldo, V; Cauvin, V; Cerutti, F; Cester, Am; Cherubini, V; Chessa, M; Chiarelli, F; Chiari, G; Chiumello, G; Cicchetti, M; Cirillo, D; Citriniti, F; Citro, G; Coccioli, Ms; Cotellessa, M; Crinò, A; D'Annunzio, G; De Berardinis, F; De Filippo, G; De Giorgi, G; De Luca, F; De Marco, R; Delvecchio, M; Faleschini, E; Federico, G; Fifi, Ar; Fontana, F; Franzese, A; Frezza, E; Frongia, A; Frontino, G; Gaiero, A; Galderisi, A; Gallo, F; Gargantini, L; Ghione, S; Giorgetti, C; Gualtieri, A; Guasti, M; Guerraggio, L; Iafusco, D; Iannilli, A; Ingletto, D; Iossa, C; Iovene, B; Iughetti, Lorenzo; Kaufmann, P; La Loggia, A; Lazzaro, N; Lenzi, L; Lera, R; Lia, R; Jonica, R; Lo Presti, D; Lombardo, F; Lorini, R; Lucchesi, S; Luceri, S; Madeo, Sf; Maffeis, C; Mainetti, B; Mammi, F; Manca Bitti, Ml; Marigliano, M; Marinari, A; Marinaro, Am; Meloni, G; Marsciani, A; Mastrangelo, L; Mastrangelo, C; Meschi, F; Minasi, D; Minenna, A; Minuto, N; Monciotti, C; Morganti, G; Mozzillo, E; Nugnes, R; Paradiso, E; Pardi, D; Pasquino, B; Patera, Ip; Pennati, C; Pepe, R; Piccini, B; Perrotta, A; Piccinno, E; Pinelli, L; Piredda, G; Pocecco, M; Ponzi, G; Prandi, E; Predieri, Barbara; Prisco, F; Quinci, M; Rabbone, I; Ricciardi, Mr; Rigamonti, A; Ripoli, C; Sabbion, A; Salardi, S; Salvatoni, A; Salvo, C; Salzano, G; Saporiti, A; Sardi, R; Scaramuzza, A; Schiaffini, R; Schieven, E; Scipione, M; Soci, C; Soro, M; Spallino, L; Stamati, F; Suprani, T; Savastio, S; Taccardi, Ra; Tarchini, L; Tomaselli, L; Toni, S; Tonini, G; Torelli, C; Tornese, G; Trada, M; Tumini, S; Valerio, G; Vanelli, M; Vanini, R; Vascotto, M; Vergerio, A; Viscardi, M; Zaffani, S; Zampolli, M; Zanatta, M; Zanette, G; Zanfardino, A; Zecchino, C; Zedda, Ma; Zucchini, S; Zuccotti, G. V.
abstract

A panel of experts of the Italian Society of Pediatric Endocrinology and Diabetology comprehensively discussed and approved the Italian recommendations regarding self-monitoring of blood glucose, continuous glucose monitoring and other measures of glycemic control in children and adolescents with type 1 diabetes. After an extensive review of the literature, we took these issues into account: self-monitoring blood glucose, continuous glucose monitoring, glycemic variability, glycosuria, ketonuria, ketonemia, glycated hemoglobin, fructosamine and glycated albumin, logbook, data downloading, lancing devices, carbohydrate counting, and glycemic measurements at school. We concluded that clinical guidelines on self-management should be developed in every country with faithful adaptation to local languages and taking into account specific contexts and local peculiarities, without any substantial modifications to the international recommendations. We believe that the National Health Service should provide all necessary resources to ensure self-monitoring of blood glucose and possibly continuous glucose monitoring of all children and adolescents with type 1 diabetes, according to the standards of care provided by these recommendations and internationally.


2014 - Severe hypoglycemia and ketoacidosis over one year in Italian pediatric population with type 1 diabetes mellitus: a multicenter retrospective observational study. [Articolo su rivista]
Cherubini, V; Pintaudi, B; Rossi, Mc; Lucisano, G; Pellegrini, F; Chiumello, G; Frongia, Ap; Monciotti, C; Patera, Ip; Toni, S; Zucchini, S; Nicolucci, A; Lera, R; Iannilli, A; Giorgetti, C; Cesaretti, A; Paparusso, Am; Alessandrelli, Mc; Scipione, M; Balsamo, C; Gallo, F; Lo Presti, D; Passanisi, S; Tumini, S; Cipriano, P; Lazzaro, N; Vergerio, A; Banin, P; Lenzi, L; Coccioli, Ms; D'Annunzio, G; Bruzzese, M; Lombardo, F; Salzano, G; Bonfanti, R; Frontino, G; Battaglino, R; Iughetti, Lorenzo; Predieri, Barbara; Cadario, F; Savastio, S; Zabadneh, N; Zanella, C; Mozzo, E; Patera, Ip; Tiozzo, S; Benevento, D; Calcaterra, V; Larizza, D; Delvecchio, M; Trada, M; Rabbone, I; Sicignano, S; Cauvin, V; Franceschi, R; Gargantini, L; Pennati, C; Bianchi, G; Salvatoni, A; Maffeis, C; Marigliano, M; Sabbion, A; Arnaldi, C; Tosini, D; Tossi, Mc; Pintaudi, B; Pellegrini, F; Lucisano, G; Valentini, M; D'Alonzo, D; Pirozzoli, C; Di Nardo, B; Memmo, R; Cianci, A.
abstract

Evaluation of incidence and correlates of severe hypoglycemia (SH) and diabetes ketoacidosis (DKA) in children and adolescents with T1DM. Retrospective study conducted in 29 diabetes centers from November 2011 to April 2012. The incidence of SH and DKA episodes and their correlates were assessed through a questionnaire administered to parents of patients aged 0-18 years. Incidence rates and incident rate ratios (IRRs) were estimated through multivariate Poisson regression analysis and multilevel analysis. Overall, 2025 patients were included (age 12.4 ± 3.8 years; 53% males; diabetes duration 5.6 ± 3.5 years; HbA1c 7.9 ± 1.1%). The incidence of SH and DKA were of 7.7 and 2.4 events/100 py, respectively. The risk of SH was higher in females (IRR = 1.44; 95%CI 1.04-1.99), in patients using rapid acting analogues as compared to regular insulin (IRR = 1.48; 95%CI 0.97-2.26) and lower for patients using long acting analogues as compared to NPH insulin (IRR = 0.40; 95%CI 0.19-0.85). No correlations were found between SH and HbA1c levels. The risk of DKA was higher in patients using rapid acting analogues (IRR = 4.25; 95%CI 1.01-17.86) and increased with insulin units needed (IRR = 7.66; 95%CI 2.83-20.74) and HbA1c levels (IRR = 1.63; 95%CI 1.36-1.95). Mother's age was inversely associated with the risk of both SH (IRR = 0.95; 95%CI 0.92-0.98) and DKA (IRR = 0.94; 95%CI 0.88-0.99). When accounting for center effect, the risk of SH associated with the use of rapid acting insulin analogues was attenuated (IRR = 1.48; 95%CI 0.97-2.26); 33% and 16% of the residual variance in SH and DKA risk was explained by center effect. The risk of SH and DKA is mainly associated with treatment modalities and strongly depends on the practice of specialist centers


2014 - Ten-Year Longitudinal Study of Thyroid Function in Children with Down's Syndrome [Articolo su rivista]
Iughetti, Lorenzo; Predieri, Barbara; Bruzzi, Patrizia; Predieri, Flavia; Vellani, G; Madeo, Sf; Garavelli, L; Biagioni, O; Bedogni, G; Bozzola, M.
abstract

Background/Aims: The natural history of thyroid function in children with Down's syndrome is relatively unknown. We hypothesized that in these patients the occurrence of thyroid dysfunction rises during development. Methods: Thyroid function was assessed yearly in 145 children with Down's syndrome, all followed from birth up to 10 years of age. Heteroskedastic binary and ordinary logistic regression for repeated measures was used to evaluate the relationship of thyroid function with continuous time. Results: Congenital hypothyroidism was detected in 7% of cases. The probability of acquired thyroid dysfunction increased from 30% at birth to 49% at 10 years (p < 0.001). The subclinical hypothyroidism was nearly stable during the follow-up. The probability of hypothyroidism increased from 7 to 24% at 10 years (p < 0.001). Positive anti-thyroglobulin antibodies were associated with higher odds of more severe hypothyroidism (odds ratio 3.6). Positive anti-thyroid peroxidase antibodies were a better predictor of more severe hypothyroidism (odds ratio 6.1). Diffuse hypoechogenicity on thyroid ultrasound was found in 34 out of 145 children. Conclusion: The probability of thyroid dysfunction increasing during development is higher than previously reported. Such children should be carefully monitored annually to early identify thyroid dysfunction.


2014 - The Role of SHOX Gene in Idiopathic Short Stature: an Italian Multicenter Study [Abstract in Rivista]
R., Minari; A., Vottero; S., Azzolini; D., Barbaro; G., Bindi; M., Bozzola; C., Burrai; G. M., Cardinale; D., Cioffi; M., Cisternino; M. S. Cocciolij M., Delvecchio; E., Fabbrizi; M., Ferrari; F., Gallarotti; F., Gallo; L., Ghizzoni; M. C., Maggio; B., Mainetti; R., Montinaro; G., Municchi; A., Panariello; M., Parpagnoli; L., Perrone; M., Petraroli; G., Radetti; A. F., Radicioni; A., Rossodivita; Mc, Salerno; S., Savasta; S., Seminara; L., Tafi; M., Tomat; A., Tummolo; M., Wasniewska; Iughetti, Lorenzo; S., Bernasconi
abstract

If we exclude the patients with Leri- Weill syndrome who presented a SHOX gene deletion in 5.4%, in our cohort of patients with ISS the incidence of SHOX gene point mutations was very low (1.5%), suggesting that the presence of mesomelia, minor skeletal abnormalities, and eventually subtle radiographic signs are essential for requiring genetic analysis properly.


2014 - Torcicollo: è solo un trauma? [Abstract in Rivista]
Fornaciari, Sara; M., Cellini; Iughetti, Lorenzo
abstract

N.A.


2014 - Una istiocitosi piuttosto rara. [Articolo su rivista]
Coccolini, Elena; Di Dio, Francesco; G., Palazzi; M., Cellini; C., Garcinuno; Paolucci, Paolo; Iughetti, Lorenzo
abstract

n.a.


2014 - Una varicella con finale a sorpresa [Articolo su rivista]
Mazzoni, Silvia; Mandese, Valentina; Cattelani, Chiara; Paolucci, Paolo; Iughetti, Lorenzo
abstract

La fascite necrotiz- zante è una patologia grave e, se non trattata, rapidamente fatale, caratterizzata da necrosi dei tessuti molli, delle fasce e della cute sovrastante, che può portare a insufficienza multiorgano con shock settico (0,4-0,5 casi su 100.000, mortalità del 20-34%).


2013 - Accuracy of SenseWear Pro2 armband to predict resting energy expenditure in childhood obesity. [Articolo su rivista]
Predieri, Barbara; Bruzzi, Patrizia; Lami, Francesca; Vellani, Giulia; Malavolti, Marcella; Battistini, Nc; Iughetti, Lorenzo
abstract

OBJECTIVE: We evaluate the accuracy of the SenseWear Pro2 Armband (SWA) in estimating resting energy expenditure (REE) in children and adolescents with obesity, using indirect calorimetry (IC) as a reference. DESIGN AND METHODS: REE was assessed using both the SWA and IC in 40 obese subjects (26 M/14 F, age 11.5±2.57 years, z-score BMI 3.14±0.53). The agreement between methods was assessed by the Bland-Altman procedure. The relationship between REE assessments and patients' characteristics was also analyzed. RESULTS: SWA- and IC-derived estimates of REE showed a significant correlation (r=0.614; P<0.001), but the SWA overestimated mean REE by 13% (P<0.001). Age and kg of fat-free mass (kgFFM) were significantly correlated with both REE estimation by SWA (r=0.434 and r=0.564; respectively) and IC (r=0.401 and r=0.518; respectively). Only kgFFM was demonstrated to be the main predictor factor of REE variability (r2 79% SWA; 75% IC). CONCLUSIONS: The SWA overestimated mean REE in childhood obesity, suggesting that the SWA and IC are not yet interchangeable methods. This would require improving the SWA by developing better algorithms for predicting REE and, probably, bias in each individual REE could be reduced by an adjustment for subjects' kgFFM.


2013 - Adipose stromal/stem cells assist fat transplantation reducing necrosis and increasing graft performance. [Articolo su rivista]
PICCINNO, MARIA SERENA; VERONESI, Elena; LOSCHI, Pietro; M., Pignatti; MURGIA, ALBA; GRISENDI, Giulia; I., Castelli; D., Bernabei; CANDINI, Olivia; P., Conte; PAOLUCCI, Paolo; E. M., Horwitz; DE SANTIS, Giorgio; IUGHETTI, Lorenzo; DOMINICI, Massimo
abstract

Autologous fat transfer (AFT) is a procedure for adipose tissue (AT) repair after trauma, burns, post-tumor resections and lipodystrophies still negatively impacted by the lack of graft persistence. The reasons behind this poor outcome are unclear and seem to involve damages in either harvested/transplanted mature adipocytes or on their mesenchymal progenitors, namely adipose stromal/stem cells (ASC), and due to post-transplant AT apoptosis and involution. A rabbit subcutaneous AT regeneration model was here developed to first evaluate graft quality at different times after implant focusing on related parameters, such as necrosis and vasculogenesis. Standard AFT was compared with a strategy where purified autologous ASC, combined with hyaluronic acid (HA), assisted AFT. Five million of autologous ex vivo isolated CD29+, CD90+, CD49e+ ASC, loaded into HA, enriched 1&nbsp;ml of AT generating an early significant protective effect in reducing AFT necrosis and increasing vasculogenesis with a preservation of transplanted AT architecture. This beneficial impact of ASC assisted AFT was then confirmed at three months with a robust lipopreservation and no signs of cellular transformation. By a novel ASC assisted AFT approach we ensure a reduction in early cell death favoring an enduring graft performance possibly for a more stable benefit in patients.


2013 - Corticotropin tests for assessment of the hypothalamus-pituitary-adrenal axis in patients with Prader-Willi syndrome [Abstract in Rivista]
G., Grugni; A., Corrias; A., Crinò; L., Beccaria; S., Di Candia; Iughetti, Lorenzo; A., Mussa; L., Ragusa; A., Salvatoni; A., Sartorio; G., Chiumello; L., Gargantini
abstract

Our data seem to confirm that CAI diagnosis in PWS patients cannot be based on a single test alone. In this light, repeat hypothalamuspituitary-adrenal testing is fully justified in this situation.


2013 - Dancing eye syndrome as first symptom of neuroblastoma. [Articolo su rivista]
Venturelli, Cristina; Guerra, A; Paolucci, Paolo; Iughetti, Lorenzo
abstract

Background: "Dancing eye syndrome", also called Kinsbourne syndrome or Opsoclonus-Myoclonus-Ataxia Syndrome (OMS) is a rare neurological disorder that in children is frequently associated to occult, low-grade neuroblastoma (NB) (&gt;50% of the cases). OMS may also be triggered by infections and it is often associated to developmental impairment and disability.Case presentation: We discuss the case of a 16 months old female with acutely onset of OMS associated to occult stage III NB.Conclusions: OMS represents a diagnostic challenge for pediatric clinicians. The suspect of OMS imposes the search for an occult NB in order to promptly treat a life-threatening event like tumor and to prevent the neurological sequels linked to OMS.


2013 - Disordini del comportamento alimentare e diabete mellito tipo 1 in età evolutiva: un'associazione più frequente di quanto ci si potrebbe attendere [Articolo su rivista]
Predieri, Barbara; Tricarico, Antonella; S. F., Madeo; Bruzzi, Patrizia; Iughetti, Lorenzo
abstract

Disordered eating behaviors are an important health issue among youth with type 1 diabetes because of their prevalence and adverse impact on metabolic control and long-term health outcomes. Individuals with type 1 diabetes may be at greater risk for the development of disordered eating due to an emphasis on nutrition management in diabetes care. Disordered eating behaviors often persist and become more serious over time, especially as weight concerns and dietary restraint increase during development. This article provides an overview of disordered eating in children and adolescents with type 1 diabetes, including prevalence, insulin omission and associated health outcomes, risk factors, and suggestion for screening and prevention.


2013 - E SE FOSSE UN PROBLEMA DI CLORO? [Abstract in Rivista]
Lucaccioni, Laura; Lugli, L.; Frassoldati, Rossella; Di Biase, Ar; Iughetti, Lorenzo
abstract

N.A.


2013 - Effect of weight loss on markers of inflammation and endothelial function in obese children and adolescents. [Abstract in Rivista]
M. L., Iezzi; P., Bruzzi; A., Salvatore; M., Saccomandi; Predieri, Barbara; Iughetti, Lorenzo
abstract

Our results demonstrated an increase of ICAM-1 and esRAGE levels, suggesting a progression of endothelial dysfunction, in asymptomatic FH children and adolescents despite a diet-induced improvement in lipid metabolism. sM may be early indicators of vascular damage and, together with familial history of premature CVD, may help clinicians in identifying children at risk before CVD develops.


2013 - Effect of 2012 earthquake on glycaemic control in children and adolescents with type 1 diabetes: the experience of Modena, Italy [Abstract in Rivista]
P., Bruzzi; E., Balestri; S., Madeo; Predieri, Barbara; Iughetti, Lorenzo
abstract

Despite an increase of HbA1c in about half of our population, Modena’s earthquake did not significantly affect the glycemic control of our patients because it did not compromise food stocks and availability of medications and equipment. Differences between CSII and MDI and the increase of microalbuminuria were hardly explainable, but the stress of dealing with the aftershock may contribute to them.


2013 - Efficacy, safety and tolerability of statin therapy in adolescents with familial hypercholesterolaemia [Abstract in Rivista]
Iughetti, Lorenzo; S., Madeo; Pietrangiolillo, Zaira; Predieri, Barbara; Bruzzi, Patrizia
abstract

A is efficient in improving lipid metabolism in FH children and adolescents. A familial history of premature CVD may influence the therapeutic compliance and let to the achievement of a better lipid profile. Side effects, especially the increase of CPK levels, are frequent on ST, especially in males and independently from current pharmacological dose.


2013 - Growth hormone therapy and respiratory disorders: long-term follow-up in PWS children. [Articolo su rivista]
Berini, J; Spica Russotto, V; Castelnuovo, P; Di Candia, S; Gargantini, L; Grugni, G; Iughetti, Lorenzo; Nespoli, L; Nosetti, L; Padoan, G; Pilotta, A; Trifirò, G; Chiumello, G; Salvatoni, A.
abstract

Adenotonsillar tissue hypertrophy and obstructive sleep apnea have been reported during short-term GH treatment in children with Prader-Willi syndrome (PWS). We conducted an observational study to evaluate the effects of long-term GH therapy on sleep-disordered breathing and adenotonsillar hypertrophy in children with PWS. We evaluated 75 children with genetically confirmed PWS, of whom 50 fulfilled the criteria and were admitted to our study. The patients were evaluated before treatment (t0), after 6 weeks (t1), after 6 months (t2), after 12 months (t3), and yearly (t4-t6) thereafter, for up to 4 years of GH therapy. The central apnea index, obstructive apnea hypopnea index (OAHI), respiratory disturbance index, and minimal blood oxygen saturation were evaluated overnight using polysomnography. We evaluated the adenotonsillar size using a flexible fiberoptic endoscope. RESULTS: The percentage of patients with an OAHI of >1 increased from 3 to 22, 36, and 38 at t1, t4, and t6, respectively (χ(2) = 12.2; P < .05). We observed a decrease in the respiratory disturbance index from 1.4 (t0) to 0.8 (t3) (P < .05) and the central apnea index from 1.2 (t0) to 0.1 (t4) (P < .0001). We had to temporarily suspend treatment for 3 patients at t1, t4, and t5 because of severe obstructive sleep apnea. The percentage of patients with severe adenotonsillar hypertrophy was significantly higher at t4 and t5 than at t0. The OAHI directly correlated with the adenoid size (adjusted for age) (P < .01) but not with the tonsil size and IGF-1 levels. CONCLUSION: Long-term GH treatment in patients with PWS is safe; however, we recommend annual polysomnography and adenotonsillar evaluation.


2013 - Holoprosencephaly: report of four cases and genotype-phenotype correlations. [Articolo su rivista]
Lami, Francesca; Carli, D; Ferrari, P; Marini, M; Alesi, V; Iughetti, Lorenzo; Percesepe, Antonio
abstract

Holoprosencephaly (HPE) is a heterogeneous disorder with variable expressivity and reduced penetrance. The causes vary from environmental factors to pure genetic forms, namely chromosomal and genomic abnormalities in up to 70% of the cases, and heterozygous mutations in at least four major genes in 17% of cases. We describe rare clinical findings, like craniovertebral hinge dysplasia, Hirschsprung’s disease and syringomyelia as part of the Currarino syndrome spectrum.


2013 - Impairment of inflammatory markers in children and adolescents with familial hypercholesterolaemia [Abstract in Rivista]
Predieri, Barbara; Malmusi, Giovanni; Lucaccioni, Laura; Patianna, VIVIANA DORA; P., Bruzzi; Iughetti, Lorenzo
abstract

Our results demonstrated an increase of ICAM-1 and esRAGE levels, suggesting a progression of endothelial dysfunction, in asymptomatic FH children and adolescents despite a diet-induced improvement in lipid metabolism. sM may be early indicators of vascular damage and, together with familial history of premature CVD, may help clinicians in identifying children at risk before CVD develops.


2013 - Incidence of SHOX deficiency in a cohort of Italian children with idiopathic short stature [Abstract in Rivista]
R., Minari; A., Vottero; S., Azzolini; D., Barbaro; C., Burrai; G. M., Cardinale; D., Cioffi; M. S., Coccioli; M., Ferrari; F., Gallarotti; F., Gallo; R., Montinaro; G., Municchi; A., Panariello; M., Parpagnoli; L., Perrone; G., Radetti; A. F., Radicioni; A., Rossodivita; M. C., Salerno; L., Tafi; A., Tummolo; M., Wasniewska; Iughetti, Lorenzo; S., Bernasconi
abstract

In our cohort of patients with ISS the incidence of SHOX gene deletions is 6%, in accordance with some of the previous reports. Auxological measurements of body proportions (mesomelia), the presence of minor skeletal abnormalities, and the search for subtle radiographic signs are important keys leading to the appropriate indication for genetic analysis.


2013 - Interactions among pro-inflammatory cytokines, IGF system and thyroid function in pre-pubertal obese subjects. [Articolo su rivista]
Street, Me; Smerieri, A; Montanini, L; Predieri, Barbara; Iughetti, Lorenzo; Valenzise, M; De Luca, F; Vigone, M; Weber, G; Maghnie, M; Bernasconi, S.
abstract

Obesity is a state of chronic inflammation. Data on IGF system are often discrepant, and their relationships with mediators of inflammation are unknown. Furthermore, changes in thyroid function have been reported. We aimed at investigating the changes in these systems, and verify any relationships among cytokines, IGF system, thyroid function and insulin-insensitivity. Fifty obese pre-pubertal children, and 55 normal-weight subjects comparable for age and sex were enrolled. Serum IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3, IL-6 and TNF-alpha were assayed. In obese children insulin, TSH and FT4 were measured also, and the HOMA-IR index was calculated. Increased IGF-II, IL-6 and TNF-alpha, and decreased IGFBP-1 and IGFBP-2 concentrations were found in obese compared to normal-weight children. The IGF-I/IGFBP-3 molar ratio was also reduced in the obese subjects. In the obese children with high HOMA-IR index, IGFBP-1 and -2 serum concentrations were significantly decreased compared with those with normal insulin sensitivity, and in the obese subjects with increased TSH, IGFBP-2 concentrations were lower, and IGFBP-3 levels were higher compared to their counterparts with normal TSH levels. Among the significant correlations, BMISDS was correlated with IGF-II, and TSH. IGF-II concentrations showed a positive relationship with IL-6. TSH was correlated with IGFBP-2 also. The data showed interactions among IL-6, IGF system, insulin sensitivity, and thyroid function with changes being related to the degree of obesity. Chronic inflammation in obese children was confirmed. Some of the changes in the IGF system could be a consequence of insulin resistance and could account also for later complications in obese subjects.


2013 - Le dislipidemie in età evolutiva: quale approccio [Articolo su rivista]
Bruzzi, Patrizia; Predieri, Barbara; Iughetti, Lorenzo
abstract

La prevenzione delle patologie cardiovascolari deve iniziare già in età pediatrica: la definizione dei parametri lipidici e di strategie di screening condivise, nonché un corretto ricorso alla terapia dietetica e farmacologica, rappresentano presupposti irrinunciabili per migliorare la gestione del bambino dislipidemico.


2013 - Metabolic syndrome in adult patients with Prader-Willi syndrome. [Articolo su rivista]
Grugni, G; Crinò, A; Bedogni, G; Cappa, M; Sartorio, A; Corrias, A; Di Candia, S; Gargantini, L; Iughetti, Lorenzo; Pagano, C; Ragusa, L; Salvatoni, A; Spera, S; Vettor, R; Chiumello, G; Brambilla, P.
abstract

BACKGROUND AND AIMS: Prader-Willi syndrome (PWS), the most common genetic cause of obesity, is characterized by elevated morbility and mortality in all ages. In this context, non-obese PWS children showed low frequency of metabolic syndrome (MetS), while a comparable prevalence was observed in obese PWS and obese controls. Aim of this study was to estimate the occurrence of MetS and its components in a large group of PWS adults, according to obesity status. METHODS AND RESULTS: A cross-sectional study was performed in 108 PWS aged 18.0-43.2 years (87 obese and 21 non-obese) and in 85 controls with nonsyndromic obesity matched for age, gender, and BMI with obese PWS. Non-obese PWS showed lower waist circumference, insulin, HOMA-index, triglycerides, diastolic blood pressure, and higher HDL-C than both obese PWS and obese controls (p &lt; 0.017). Obese PWS showed higher glucose and systolic blood pressure than both non-obese PWS and obese controls (p &lt; 0.017). MetS was found in 1/21 (4.8%) non-obese PWS, 36/87 (41.4%) obese PWS and 39/85 (45.9%) obese controls. Non-obese PWS showed lower frequency for each MetS component as compared with obese PWS and obese controls. PWS patients with deletion of the chromosome 15q11-13 showed a lower risk for low HDL-C (p &lt; 0.01) and a trend towards a lower MetS risk (p &lt; 0.06) compared to subjects without deletion. CONCLUSION: Our findings suggest the main role that obesity status plays on the individual metabolic risk clustering in PWS adults. Early identification of MetS could be helpful to improve morbidity and prevent mortality in such patients.


2013 - Modello regionale di presa in carico del bambino sovrappeso e obeso [Pubblicazioni Fonti inedite]
Fridel, M.; Biavati, C.; Daghio, M.; Di Stani, M.; Fabbri, A.; Gambarara, D.; Gibin, A. M.; Gualand, V.; Iaia, M.; Iughetti, Lorenzo; Lucchi, L.; Mattioli, M.; Pascucci, M. G.; Spettoli, D.; Rauti, A.; Ricci, R.; Tripodi, A.
abstract

n.a.


2013 - Multicenter study on final height and body mass index in adult survivors of childhood acute lymphoblastic leukaemia treated on AIEOP 87-2000 protocols excluding cranial radiotherapy [Abstract in Rivista]
P., Bruzzi; Predieri, Barbara; S., Madeo; A., Rossodivita; A., Marsciani; M. E., Street4; A., Corrias; Iughetti, Lorenzo
abstract

In our study, survivors of childhood ALL treated with CT experienced reduction in height-SDS during CT that persisted until FH. Nevertheless, they generally seemed to achieve a normal FH with a BMI within the normal range. Even if all patients experienced an increase of BMISDS during CT, only F seemed at risk to conserve it until FH.


2013 - Serum thyrotropin concentration in children with isolated thyroid nodules. [Articolo su rivista]
Mussa, A; Salerno, Mc; Bona, G; Wasniewska, M; Segni, M; Cassio, A; Vigone, Mc; Gastaldi, R; Iughetti, Lorenzo; Santanera, A; Capalbo, D; Matarazzo, P; De Luca, F; Weber, G; Corrias, A.
abstract

OBJECTIVE: To investigate the correlation between serum thyroid-stimulating hormone (TSH) concentration and nodule nature in pediatric patients with thyroid nodules, with the aim of identifying a marker able to differentiate benign and malignant nodules. STUDY DESIGN: This was a retrospective analysis of serum TSH concentrations in a multicentric case series of 125 pediatric patients with benign and malignant thyroid nodules. RESULTS: Of the 125 patients, 99 had benign thyroid nodules and 26 had differentiated thyroid cancer (24 papillary and 2 follicular). Final diagnosis was based on surgery in 57 cases and on a benign cytology plus clinical follow-up in 68 cases. Serum TSH concentration was significantly higher in patients with thyroid cancer compared with those with benign nodules (3.23 ± 1.59 mU/L vs 1.64 ± 0.99 mU/L; P < .001). Binary logistic regression analysis revealed that serum TSH was the sole predictor of malignancy (P < .001). Dividing the patient cohort into 5 groups based on serum TSH quintiles (TSH cutoffs 0.40, 1.00, 1.50, 1.80, and 2.80 mU/L), we observed that cancer prevalence increased in parallel with serum TSH (P < .001), with respective rates of 0%, 4%, 16%, 32%, and 52% in the 5 quintile groups. CONCLUSION: Because cases with malignant nodules are most likely seen in the upper normal serum TSH range (ie, >2.8 mU/L), serum TSH concentration can serve as a predictor of thyroid cancer in pediatric patients with thyroid nodules and can inform the decision of when to submit patients to further investigation by cytology.


2013 - SINDROME DA ENCEFALOPATIA POSTERIORE REVERSIBILE (PRES): RARO ESORDIO DI UNA GLOMERULONEFRITE POST-STREPTOCOCCICA IN ETA’ PEDIATRICA [Abstract in Rivista]
Cioni, Vera; Guidotti, Isotta; A., Dozza; S., Cantatore; Paolucci, Paolo; Iughetti, Lorenzo
abstract

N.A.


2013 - Surface rendering of external genitalia of a fetus at the 32nd week of gestation affected by partial androgen insensitivity syndrome. [Articolo su rivista]
Mazza, V; Bertucci, Emma; Latella, S; Cani, C; Ceccarelli, P; Iughetti, Lorenzo; Baldinotti, F; Percesepe, Antonio
abstract

Objectives. To demonstrate the feasibility of the prenatal diagnosis of partial androgen insensitivity syndrome by 3D-4D ultrasound. Methods. To report prenatal diagnosis of partial androgen insensitivity syndrome at 32nd week of gestation by 3D-4D ultrasound in a fetus with a 46XY karyotype, testing negative to the mutation analysis of SRY gene and the 5α-reductase 2 gene (SRD5A2). Results. 3D-4D surface rendering allows the detection of external and internal genital malformations and can address the prenatal diagnosis of PAIS and can exclude associated complications. Conclusions. Prenatal diagnosis of PAIS allows an adequate parental counseling and an early optimal management of the condition, not only for the psychological and social reflections but also for the avoidance of complications and postnatal morbidity due to misdiagnosis or delays in the treatment of the genital ambiguity.


2013 - The effect of prolonged GH treatment on upper airways and sleep-disordered breathing of 50 non-severely obese children with Prader-Willi syndrome [Abstract in Rivista]
J., Berini; S., Di Candia; V., Spica Russotto; Iughetti, Lorenzo; L., Gargantini; A., Pilotta; G., Grugni; G., Padoan; M., Cisternino; G., Trifirò; P., Castelnuovo; G., Chiumello; A., Salvatoni
abstract

Our findings confirm the favorable effect of long-term GH treatment on respiratory function of PWS, however the increase of OAI and upper airways narrowing reccommend ENT and PSG follow-up.


2013 - Thyroid disorders in children and adolescents with Prader-Willi syndrome: data from 299 Italian patients [Abstract in Rivista]
Iughetti, Lorenzo; G., Vivi; A., Balsamo; G., Chiumello; A., Corrias; A., Crinò; M., Delvecchio; L., Gargantini; N. A., Greggio; G., Grugni; U., Hladnik; A., Pilotta; L., Ragusa; A., Salvatoni; M., Wasniewska; Predieri, Barbara
abstract

Thyroid axis dysfunction seems to be a frequent feature (10.7%) in subjects with PWS compared to the general population. However, we found a lower prevalence of HT in our PWS subjects respect to other national database that included fewer patients. Pediatricians should be aware of this association so this possibility is considered while evaluating PWS patients.


2012 - A proposal of a decision-making score for GH treatment modulation in Prader-Willi syndrome. [Abstract in Rivista]
A., Salvatoni; J., Berini; G., Chiumello; A., Crinò; S., Di Candia; L. i., Gargantini; G., Grugni; Iughetti, Lorenzo; A., Luce; V., Milan; G., Musolino; P., Sogno Valin; V., Spica Russotto; G., Trifirò
abstract

Our proposal of a score to be used in the modulation of GH therapy in Prader-Willi syndrome, before becoming a tool for standardization of this treatment, requires first to be tested on a wider sample of patients in order to obtain general consensus.


2012 - Abdominal adiposity and cardiovascular risk factors in adolescents with type 1 diabetes. [Articolo su rivista]
Valerio, G; Iafusco, D; Zucchini, S; Maffeis, C; Lera, R; Cherubini, V; Biagioni, M; Rollo, A; Gallo, F; Toni, S; Guasti, M; Mammì, F; Bruzzese, M; Lombardo, F; Salzano, G; Scaramuzza, A; Zuccotti, Gv; Sacco, H; Iughetti, Lorenzo; Predieri, Barbara; Calcaterra, V; Federico, G; Marchi, B; Cerutti, F; Rabbone, I; Cardinale, G; De Berardinis, F; De Donno, V; Franzese, A; Mozzillo, E; Prisco, F; Zedda, Ma; Ripoli, C.
abstract

AIM: To analyze the prevalence of abdominal adiposity and other traditional risk factors for cardiovascular disease in a large sample of Italian adolescents with type 1 diabetes mellitus (T1DM). METHODS: T1DM adolescents (n=412 age: 17.3 ± 0.9 years) were enrolled from 18 clinical centres. Anthropometric and laboratory parameters, blood pressure and data on insulin treatment were registered. Metabolic syndrome (MetSy) was defined according to the International Diabetes Federation criteria. RESULTS: Abdominal obesity was the most common risk factor (20.1%) in females, while hypertension in males (25.1%). MetSy was found in 9.5% patients, predominantly in females. Patients with MetSy exhibited higher insulin requirement per body surface area and higher glycated hemoglobin than patients without MetSy. Overweight/obese patients had a much higher prevalence of MetSy than normal weight patients. The logistic regression analysis showed that just waist-to-height ratio and insulin dose per body surface area contributed to discriminate subjects with the MetSy from those without. CONCLUSION: Adolescence is a critical period in determining risk of future vascular complications in T1DM. Pediatric diabetologists need to be aware of the considerable occurrence of abdominal adiposity and MetSy in T1DM patients, particularly in females, and should make every effort to achieve normal weight and better health outcomes


2012 - Assessment of central adrenal insufficiency in children and adolescents with Prader-Willi syndrome. [Articolo su rivista]
Corrias, A; Grugni, G; Crinò, A; Di Candia, S; Chiabotto, P; Cogliardi, A; Chiumello, G; De Medici, C; Spera, S; Gargantini, L; Iughetti, Lorenzo; Luce, A; Mariani, B; Ragusa, L; Salvatoni, A; Andrulli, S; Mussa, A; Beccaria, L.
abstract

OBJECTIVE: A recent study evidenced by metyrapone test a central adrenal insufficiency (CAI) in 60% of Prader-Willi syndrome (PWS) children. These results were not confirmed in investigations with low [Low-Dose Tetracosactrin Stimulation Test (LDTST), 1 μg] or standard-dose tetracosactrin stimulation tests. We extended the research by LDTST in paediatric patients with PWS. DESIGN: Cross-sectional evaluation of adrenal stress response to LDTST in a PWS cohort of a tertiary care referral centre.PATIENTS: Eighty-four children with PWS. MEASUREMENTS: Assessment of adrenal response by morning cortisol and ACTH dosage, and 1-μg tetracosactrin test. Response was considered appropriate when cortisol reached 500 nm; below this threshold, patients were submitted to a second test. Responses were correlated with the patients' clinical and molecular characteristics to assess genotype-phenotype correlation. RESULTS: Pathological cortisol peak responses to the LDTST were registered in 12 patients (14.3%) who had reduced basal (169.4 ± 83.3 nm) and stimulated (428.1 ± 69.6 nm) cortisol levels compared to patients with normal responses (367.1 ± 170.6 and 775.9 ± 191.3 nm, P < 0.001). Body mass index standard deviation score was negatively correlated with basal and peak cortisol levels (both P < 0.001), and the patients' ages (P < 0.001). In patients with deletion on chromosome 15, the cortisol peak was significantly lower than that in uniparental disomy (UPD) cases (P = 0.030). At multiple regression analysis, the predictors of peak response were basal cortisol, age, and UPD subclass (r(2) = 0.353, P < 0.001). Standard-dose (250 μg) tetracosactrin test confirmed CAI in 4/12 patients (4.8% of the cohort).CONCLUSIONS: Our results support the hypothesis that, albeit rare, CAI may be part of the PWS in childhood.


2012 - Can inflammatory marker levels help in detecting early complications of childhood obesity? [Abstract in Rivista]
Bruzzi, Patrizia; Iughetti, Lorenzo; Cattelani, Chiara; Patianna, VIVIANA DORA; Vellani, Giulia; S. F., Madeo; Predieri, Barbara
abstract

Considering the high levels of ICAM-1 and the correlation of VCAM-1 with measures of adiposity, our concern is on the correct approach in managing our obese subjects to precociously indentify the formation of the atherosclerotic plaque. Moreover, in our study inflammatory marker were not identified as predictor factors for IR, MS, and NAFLD so other studies are needed to better understand which other markers can help us for the precocious diagnosis of these complications.


2012 - Combined therapy with insulin and rGH in thirteen Italian patients with type 1 diabetes (T1DM) and growth disorders [Abstract in Rivista]
S., Zucchini; G., Pozzobon; R., Bonfanti; S., Vannelli; I., Rabbone; M., Maghnie; C., Bizzarri; S., Tumini; L., Lenzi; M. C., Maggio; D., Iafusco; M., Marigliano; V., Cherubini; Iughetti, Lorenzo
abstract

Combined GH and insulin therapy are rarely prescribed in pediatric pts because the association of GHD and T1DM is rare and maybe for the difficulties in managing a double therapy with opposite effects on glucose metabolism. Objective and hypotheses: To investigate on the attitude of pediatric endo-diabetologists in treating these pts. Methods: Data were collected from over 50 centres belonging to the ISPED. The inclusion criterion was based on the double therapy for at least 6 months with insulin due to T1DM, and rGH, due to growth impairment. Results: Most centres stated that the use of combined therapy was considered uncomfortable and frequently avoided, whereas 10 centres reported the treatment of 13 pts (7M, 6F). In 7 pts T1DM was the first diagnosis (age at onset from 1.5 to 9.5 yrs) and they were treated with insulin (group 1) and with rGH subsequently (after 0.5-9.75 yrs) due to idiopathic GHD in 4 pts, Turner s. in 1 pt, Leri-Weill s. in 1 pt and bone dysplasia in 1 pt. In 6 pts rGH therapy was started first (age at start 2.5-12 yrs) due to idiopathic GHD in 4 pts, organic GHD in 1 pt and Turner s. in 1 pt. Height SDS at the start of rGH therapy ranged from -2.5 to -3.9. Longest duration of rGH therapy was 7 yrs and 5 pts are still treated. Insulin schedule was with MDI in 10 pts and with CSII in the remaining 3. In the 7 pts of group 1, mean insulin dose increased during the first 6 months after rGH start from 0.68 to 1.06 U/kg (p=0.03). HbA1c was not modified after 6 months compared to the baseline value (7.62±0.8 vs 7.76±0.57). In the pt with Leri-Weill s. rGH therapy was stopped due to impaired metabolic control. No significant side-effects during the treatment were reported. Conclusions: Double therapy with insulin and GH is uncommonly performed in pediatric patients. Despite a higher insulin requirement, metabolic control in patients with T1DM was not impaired significantly by the simultaneous treatment. Our data suggest that GH is not an absolute contraindication for treatment of children with T1DM and growth disorders.


2012 - Compartment syndrome after viper-bite in toddler:case report and review of literature [Articolo su rivista]
Pietrangiolillo, Zaira; Frassoldati, Rossella; V., Leonelli; R., Freschi; A., Russomando; Lucaccioni, Laura; Iughetti, Lorenzo
abstract

Snakebites in Italy are a rare source of severe medical condition, except in case of venomous snakes. The venom causes both local and/or systemic complication which may determine death in 6-60hours, particularly in children and the elderly. In fact, the same amount of venom affects children more severely than adults because of the reduced total dilution volume in children. The only specific and conflicting therapy for venomous snakebite is to administer the appropriate anti-venom; the remaining therapy is symptomatic and supportive.We describe the case of a 22 months old child who, despite appropriate symptomatic treatment, developed severe signs and an acute compartment syndrome of the right upper limb, a rare complication of venom snakebite. Administration of antivenom and fasciotomy were needed to resolve the acute episode permitting a positive outcome. On the basis of literature review and our experience we hypothesizean algorithm for the treatment of these patients.


2012 - Confocal microscopy: Improving our understanding of nevogenesis [Capitolo/Saggio]
De Pace, B; Ferrari, B; Predieri, Barbara; Iughetti, Lorenzo; Veneziano, L; Zalaudek, I; Argenziano, G; Longo, Caterina; Pellacani, Giovanni
abstract

n.a.


2012 - E per finire...qualcosa di dolce [Abstract in Rivista]
Pagano, R.; Vivi, Giulia; Tosetti, Giulia; Paolucci, Paolo; Iughetti, Lorenzo
abstract

La sindrome di Sweet associata ai tumori maligni (MASS) può presentarsi come sindrome paraneoplastica in soggetti nei quali è già stato diagnosticato una neoplasia o in presenza di una discrasia ematologica e si associa frequentemente a leucemia mieloide acuta. La dermatosi può precedere, seguire o essere concomitante con la diagnosi di un tumore. La MASS può rappresentare un prodromo cutaneo, sia di un tumore viscerale non diagnosticato, sia di una recidiva tumorale. La patogenesi è multifattoriale e non è stata stabilita in modo definitivo. Le citochine hanno un ruolo eziologico predominante. I corticosteroidi sistemici rappresentano lo standard terapeutico di riferimento. L'applicazione topica di corticosteroidi ad alta potenza o di corticosteoidi intralesionali è efficace per il trattamento delle lesioni localizzate. Le lesioni possono risolversi spontaneamente senza alcun intervento terapeutico, possibili le recidive.


2012 - Ectima gangrenoso in corso di sepsi neonatale da Pseudomonas aeruginosa [Abstract in Rivista]
Bottosso, Emanuele; Lucaccioni, Laura; C., Cano; B., Mordini; Iughetti, Lorenzo; M. A., Bianchini; P., Repetto
abstract

La sepsi da Pseudomonas aeruginosa (PA) è un evento raro nel neonato a termine, in assenza di fattori predisponenti quali immunodeficienze congenite o acquisite. In età pediatrica può associarsi a discoagulopatia, neutropenia, manifestazioni cutanee (ectima gangrenoso) e otologiche.


2012 - Emerging effects of early environmental factors over genetic background for type 1 diabetes susceptibility: evidence from a Nationwide Italian Twin Study. [Articolo su rivista]
Nisticò, L; Iafusco, D; Galderisi, A; Fagnani, C; Cotichini, R; Toccaceli, V; Stazi, Ma; Cherubini, V; Iannilli, A; Paparusso, Am; Cavallo, L; Zecchino, C; de Filippo, G; Gargantini, L; Salardi, S; Zucchini, S; Maltoni, G; Pasquino, B; Kaufmann, P; Buzi, F; Prandi, E; Gallo, F; Cicchetti, M; Castaldo, E; Citriniti, F; Chiarelli, F; Tumini, S; Di Stefano, A; Sperlì, D; De Marco, R; Banin, P; Toni, S; Lenzi, L; Del Vecchio, M; Lorini, R; D'Annunzio, G; Ingletto, D; Scaramuzza, A; Zuccotti, Gv; Chiumello, G; Meschi, F; Bonfanti, R; Frontino, G; de Luca, F; Lombardo, F; Salzano, G; Iughetti, Lorenzo; Franzese, A; Buono, P; De Simone, I; Prisco, F; Cocca, A; Cadario, F; Monciotti, Cm; Savio, V; Cardella, F; Vanelli, M; Chiari, G; Errico, K; Iovane, B; Calcaterra, V; Citro, F; Cantoni, S; Marsciani, A; Cappa, M; Patera, Pi; Schiaffini, R; Sulli, N; Spoletini, M; Cerutti, F; Rabbone, I; Sicignano, S; Cauvin, V; Bellizzi, M; Tonini, G; Faleschini, E; Salvatoni, A; Pinelli, L; Maffeis, C; Contreas, G.
abstract

CONTEXT: The incidence of type 1 diabetes has been increasing over time. OBJECTIVE: We estimated the genetic and environmental components of type 1 diabetes susceptibility in a twin cohort of recent-onset cases to explore the sources of changing disease epidemiology. DESIGN: We linked the population-based Italian Twin Registry with 14803 type 1 diabetes records from 36 pediatric diabetes care centers throughout Italy, except Sardinia, and identified 173 diabetic twins. Patients were positive for at least one autoantibody to islet cell, glutamate decarboxylase, tyrosine phosphatase, insulin, or zinc transporter 8 and were insulin dependent since their diagnosis. Zygosity was determined by DNA genotyping or by questionnaire. OUTCOME MEASURES: We estimated proband-wise concordance, cotwin recurrence risk with Kaplan-Meier method, and genetic and environmental proportions of susceptibility variance by structural equation models. RESULTS: We recruited 104 diabetic twins (53 males) from 88 pairs (34 monozygotic, 54 dizygotic) and one triplet. The mean age at diagnosis was 8.1 yr (range 1.1-20.5 yr), and the median year of diagnosis was 2002. Proband-wise concordances were 45.5 and 16.4% in monozygotic and dizygotic pairs (P = 0.01). Recurrence risks in monozygotic and dizygotic cotwins were 37 and 12% after 10 yr from the proband's diagnosis (P = 0.005). Genetic contribution to type 1 diabetes susceptibility was 40% (95% confidence interval 8-78), and the shared and individual-specific environmental components were 51% (14-77) and 9% (4-19), respectively. CONCLUSIONS: In addition to the moderate genetic effects on type 1 diabetes susceptibility, our results draw attention to the substantial shared environmental effects, suggesting that exposures in fetal or early postnatal life may contribute to the increasing incidence of the disease.


2012 - Evaluation of the quality of life in children and adolescents with type 1 diabetes, coeliac disease and healthy controls. [Abstract in Rivista]
Patianna, VIVIANA DORA; M., Pugliese; Predieri, Barbara; Bruzzi, Patrizia; Vellani, Giulia; A. R., Di Biase; S. F., Madeo; Iughetti, Lorenzo
abstract

Our results demonstrate that children and adolescents with chronic disease, despite a good adherence to therapy, have impairment in psychosocial health fx. Our data disagree with common opinion that children with CD have a better adaptation and functioning. These findings contribute significant information on the effects of pediatric chronic conditions on generic QOL from the perspectives of children. It is conceivable that a immediate multidisciplinary approach to patients with T1DM can be responsible for this differences.


2012 - Hearing growth defects in turner syndrome [Capitolo/Saggio]
Iughetti, Lorenzo
abstract

Turner syndrome (TS) is one of the most common chromosomal abnormalities, occurring in about 50 per 100,000 female live births characterized by the total or partial loss of one X-chromosome in all or some cells. Frequently observed manifestations of TS include short stature, lymphedema, cardiac abnormalities, gonadal dysgenesis, dysmorphic features, ear and hearing problems, and a variety of other problems. Conductive hearing loss (CHL) in patients (pts) with TS is due to recurrent otitis media with effusion, chronic middle ear infection, and cholesteatoma probably as the result of malfunction of the Eustachian tube associated with lymphedema and anatomic shortening of the skull base. The high prevalence of middle ear infections and CHL in TS are probably due to growth disturbances of the structures from the first and second branchial arches. Sensorineural hearing loss (SNHL) is also reported in TS and the hearing decline seems to consist of two patterns: a mid-frequency dip (0.5-3 kHz region) (MF-HL) and a high-frequency loss (&gt;3 kHz region) (HF-HL). SNHL is associated with genotype and phenotype. It seems that SNHL in these pts can become clinically evident during childhood or adolescence, progressive with time, and is independent of middle ear diseases. The evaluation in follow-up of hearing impairment shows that the high-frequency HL remained stable in time. Instead, SNHL with typical dip had a progressive decline. The rate of hearing loss is high at all frequencies but most prominent in the mid-frequency region and the presence of a mid-frequency dip is an especially strong predictor for a progressive decline of hearing. Hearing loss (HL) could have an important impact on social functioning for pts with TS. Clinicians proposed a regular audiological follow-up in TS, especially during childhood, to prevent important middle ear anatomic sequelae and to identify HL at an early stage.


2012 - Human amniotic epithelial cells as a reliable source for diabetes stem-cell therapy [Abstract in Rivista]
Okere, Brenard; Patianna, Viviana; Saraceni, Serena; Predieri, Barbara; Paolucci, Paolo; Iughetti, Lorenzo
abstract

Objectives: Human placenta is available as a discarded tissue, which provides a rich population of multipotent stem cells. Amongst them, HAECs represent a promising resource for regenerative medicine. In the present study we cultured HAECs in serum-free and defined media preserving their phenotypic and genetic traits. Then we verified the mesodermic differentiation capacity of HAECs and finally evaluated their pancreatic differentiative potential. We hypothesize that HAECs, cultured in such conditions, may show the same or better differentiation rate of HAECs cultured in standardized serum-rich media when induced into insulin producing cells. Methods: Placenta samples were collected, HAECs were isolated and cultured in standard serum-rich medium and serum-free optimized media. We used RT-PCR to assess stem cell markers. Mesodermic osteogenic induction was performed for each media using the same induction cocktail. Differentiation was evaluated through Alizarin red staining and qPCR for osteogenic gene expression. To study HAECs’ pancreatic differentiation ability, Nicotinamide was added to each medium. Pancreatic markers expression and immune-phenotype profile were assessed respectively with qPCR, fluorescence-activated cell sorting analysis or immune-fluorescence. Results: Serum-free media sustained HAECs’ growth and stem cell potential (OCT4, NANOG, SOX2). Alizarin red assay showed mineralization in all the culture conditions, confirmed by qPCR for key osteogenic markers such as OCN, RUNX2 and COL1A1. Preliminary pancreatic induction revealed expression of stemness marker NESTIN, typical of pancreatic progenitor cells, and pancreatic markers INSULIN and PDX1. Conclusion: These data indicate that serum is not essential for HAECs culture and differentiation. Serum-free culture conditions could simplify the transition from laboratory to clinical practice. For this reason HAECs might be a reliable, ethical-free source of insulin producing cells in clinical applications.


2012 - Human amniotic epithelial cells (HAECs): a reliable source of insulin producing cells? [Abstract in Rivista]
Okere, Bernard; Patianna, VIVIANA DORA; S., Saraceni; Predieri, Barbara; Paolucci, Paolo; Iughetti, Lorenzo
abstract

of any ethical concern, providing a rich population of multipotent stem cells. Amongst them, HAECs represent a potentially unlimited source of functional pancreatic endocrine cells. Objective and hypotheses: The aim of our study is to culture HAECs in serum-free condition preserving their phenotypic and genetic traits. Then we verify the capacity of HAECs to differentiate into at least one mesodermic lineage and we evaluate their pancreatic differentiative potential. We hypothesize that HAECs, cultured in serum-free media may show the same or better differentiation rate of HAECs cultured in standardized serum-rich conditions when induced into insulin producing cells Methods: Placenta samples were collected, HAECs were isolated and cultured in standard serum-rich medium and serum-free optimized media. We used RT-PCR to assess stem cell markers. Mesodermic osteogenic induction was performed for each media using the same induction cocktail. Differentiation was evaluated through Alizarin red staining and RT-PCR for osteogenic gene expression. To study HAECs’ pancreatic differentiation ability, nicotinamide was added to each medium. Pancreatic markers expression and immune-phenotype profile were assessed respectively with RT-PCR and fluorescence-activated cell sorting analysis. Results: Serum-free media sustained HAECs’ growth and stem cell potential (OCT4, NANOG, SOX2). Alizarin red assay showed mineralization in all the culture conditions, confirmed by RT-PCR for key osteogenic markers such as OCN RUNX2 and COL1A1. Preliminary pancreatic induction revealed expression of stemness marker NESTIN, common in pancreatic progenitor cells, and pancreatic markers INSULIN and NKX2.2. Conclusions: These data indicate that serum is not essential for HAECs culture and differentiation. Serum-free culture conditions could simplify the transition from laboratory to clinical practice. For this reason HAECs might be a possible and reliable source of insulin producing cells in clinical applications


2012 - Impact of nutrition since early life on cardiovascular prevention [Articolo su rivista]
Guardamagna, O.; Abello, F.; Cagliero, P.; Iughetti, Lorenzo
abstract

The cardiovascular disease represents the leading cause of morbidity and mortality in Western countries and it is related to the atherosclerotic process. Cardiovascular disease risk factors, such as dyslipidemia, hypertension, insulin resistance, obesity, accelerate the atherosclerotic process which begins in childhood and progresses throughout the life span. The cardiovascular disease risk factor detection and management through prevention delays the atherosclerotic progression towards clinical cardiovascular disease. Dietary habits, from prenatal nutrition, breastfeeding, complementary feeding to childhood and adolescence nutrition play a basic role for this topic.The metabolic and neuroendocrine environment of the fetus is fundamental in the body's "metabolic programming". Further several studies have demonstrated the beneficial effects of breastfeeding on cardiovascular risk factors reduction. Moreover the introduction of complementary foods represents another important step, with particular regard to protein intake. An adequate distribution between macronutrients (lipids, proteins and carbohydrates) is required for correct growth development from infancy throughout adolescence and for prevention of several cardiovascular disease risk determinants in adulthood.The purpose of this review is to examine the impact of nutrition since early life on disease.La malattia cardiovascolare rappresenta la principale causa di morbilità e mortalità dei paesi occidentali ed è correlata a degenerazione vascolare aterosclerotica. I fattori di rischio cardiovascolari quali dislipidemia, ipertensione, insulino resistenza e obesità accelerano tale processo il cui esordio è noto sin dell'età pediatrica ed evolve nel corso della vita. L'individuazione e la cura dei fattori di rischio cardiovascolari mediante la prevenzione dei fattori causali ritardano la progressione dell'aterosclerosi e l'insorgenza dei sintomi cardiovascolari. La nutrizione svolge un ruolo preventivo fondamentale sin dall'epoca prenatale e nelle diverse età della crescita.La condizione metabolica e neuro-endocrino cui è sottoposto il feto è rilevante per la "programmazione metabolica". E' dimostrata inoltre l'importanza delle modalità di allattamento e divezzamento con particolare interesse per l'assunzione di proteine nel controllo dei fattori di rischio cardiovascolari. La corretta distribuzione di macronutrienti (lipidi, proteine e carboidrati) dall'infanzia all'adolescenza favorisce una crescita corretta e risulta utile a prevenire l'insorgenza dei determinanti di rischio di malattia cardiovascolare in età adulta.Nella presente review verrà esaminato l'impatto della nutrizione dalle più precoci fasi delle vita sul rischio cardiovascolare. © 2012 Guardamagna et al.; licensee BioMed Central Ltd.


2012 - Impaired GH Secretion in Patients with SHOX Deficiency and Efficacy of Recombinant Human GH Therapy. [Articolo su rivista]
Iughetti, Lorenzo; Vannelli, S; Street, Me; Pirazzoli, P; Bertelloni, S; Radetti, G; Capone, L; Stasiowska, B; Mazzanti, L; Gastaldi, R; Maggio, Mc; Predieri, Barbara
abstract

Background/Aims: Mutations of the short stature homeobox-containing (SHOX) gene on the pseudoautosomal region of the sex chromosomes cause short stature. GH treatment has been recently proposed to improve height in short patients with SHOX deficiency. The aim of this study was to evaluate GH secretion and analyze growth and safety of recombinant human GH (rhGH) therapy in short children and adolescents with SHOX deficiency. Patients and Design: We studied 16 patients (10 females; 9.7 ± 2.9 years old; height -2.46 ± 0.82 standard deviation score, SDS) with SHOX deficiency. All subjects underwent auxological evaluations, biochemical investigations, and were treated with rhGH (0.273 ± 0.053 mg/kg/week). Results: Impaired GH secretion was present in 37.5% of the studied subjects. Comparing baseline data with those at the last visit, we found that rhGH treatment improved growth velocity SDS (from -1.03 ± 1.44 to 2.77 ± 1.95; p = 0.001), height SDS (from -2.41 ± 0.71 to -1.81 ± 0.87; p &lt; 0.001), and IGF-1 values (from -0.57 ± 1.23 to 0.63 ± 1.63 SDS, p = 0.010) without affecting body mass index SDS. Height SDS measured at the last visit was significantly correlated with chronological age (r = -0.618, p = 0.032), bone age (r = -0.582, p = 0.047) and height SDS (r = 0.938, p &lt; 0.001) at the beginning of treatment. No adverse events were reported on rhGH therapy which was never discontinued. Conclusion: These data showed that impaired GH secretion is not uncommon in SHOX deficiency subjects, and that rhGH therapy may be effective in increasing height in most of these patients independent of their GH secretory status, without causing any adverse events of concern.


2012 - Incidental diagnosis of thoracic ganglioneuroblastoma in a3 years old female with wheezing [Articolo su rivista]
Lucaccioni, Laura; Bigi, Elena; C., Cano Garcinuno; Paolucci, Paolo; Iughetti, Lorenzo
abstract

Ganglioneuroblastoma (GNB) is a cancer of the peripheral sympathetic nervous system and represents the 30% of cases of Neuroblastoma.When originates from thoracic ganglia it may appear very late, with severe symptoms like respiratory distress or neurological dysfunctions.We present an incidental diagnosis of thoracic GNB, discovered by a chest radiography during a recurrent wheezing unresponsive to bronchodilators. The early diagnosis allowed a precocious treatment probably improving the outcome.


2012 - Intossicazione da salmeterolo e QTc “ballerino”... [Abstract in Rivista]
Spaggiari, Eugenio; Lami, Francesca; Baccilieri, Federica; Frassoldati, Rossella; Balestri, Eleonora; C., Rossi; I., Maini; P., Bergonzini; Iughetti, Lorenzo
abstract

L., maschio, 11 anni, veniva condotto in PS per palpitazioni e vomito preceduti da nausea e dolore addominale insorti dopo avere inalato per gioco circa 15-20 puff di salmeterolo + fluticasone (25 µg/125 µg). All’ECG riscontro di tachicardia sinusale, blocco di branca destra incompleto e allungamento dell’intervallo QTc (0,47 sec). Su indicazione del CAV di Milano si disponeva reidratazione ev, monitoraggio ECG fino a risoluzione della tachicardia, controllo elettroliti (in particolare livelli di potassiemia) e osservazione per alcune ore in considerazione dell’emivita del farmaco (7 ore). Agli esami ematici si evidenziava ipopotassiemia (2,6 mEq/l), con normalizzazione spontanea ai controlli successivi. Ai successivi controlli ECG persisteva allungamento del QTc per cui il collega cardiologo suggeriva ricovero ed esecuzione di Holter-ECG. Una prima registrazione eseguita il giorno seguente l’assunzione accidentale evidenziava aritmia sinusale respiratoria notturna, isolate extrasistoli ventricolari singole monomorfe e associata variabilità del QTc da 0,35 sec a 0,47 sec. Alla registrazione di controllo dopo quattro giorni l’Holter ECG ha evidenziato normalizzazione dell’intervallo QTc. L’allungamento dell’intervallo QT può avere cause congenite (sindrome del QT lungo) o acquisite. Questa condizione ha una rilevanza clinica notevole poiché può essere causa di tachiaritmie ventricolari potenzialmente fatali (torsione di punta)1. Vari fattori predispongono all’allungamento del QT (sesso femminile, età, cardiopatie, aumento degli ormoni tiroidei, ipopotassiemia, alterazioni nel metabolismo dei farmaci) ma una delle cause più comuni è l’uso di farmaci2: antiaritmici, antibiotici, antiemetici, anestetici, antidepressivi. Tra essi è compreso anche il salmeterolo3, farmaco agonista dei recettori β2-adrenergici a lunga durata d’azione utilizzato nel trattamento dell’asma e della BPCO spesso in associazione ad un corticosteroide. I principali effetti collaterali, che compaiono soprattutto in caso di sovradosaggio, sono: cefalea, vertigini, tremori, tachicardia, dolore toracico4. Tra questi si dovrebbe tenere in considerazione anche l’allungamento dell’intervallo QT e le complicanze che ne possono derivare.


2012 - Management of children and adolescents with severe obesity. [Articolo su rivista]
Valerio, G; Licenziati, Mr; Tanas, R; Morino, G; Ambruzzi, Am; Balsamo, A; Brambilla, P; Bruzzi, Patrizia; Calcaterra, V; Crinò, A; De Falco, R; Franzese, A; Giordano, U; Grugni, G; Iaccarino Idelson, P; Iughetti, Lorenzo; Maffeis, C; Manco, M; Miraglia Del Giudice, E; Mozzillo, E; Zito, E; Bernasconi, S.
abstract

Obesity is a complex public health issue. Recent data indicate the increasing prevalence and severity of obesity in children. Severe obesity is a real chronic condition for the difficulties of long-term clinical treatment, the high drop-out rate, the large burden of health and psychological problems and the high probability of persistence in adulthood. A staged approach for weight management is recommended. The establishment of permanent healthy lifestyle habits aimed at healthy eating, increasing physical activity and reducing sedentary behavior is the first outcome, because of the long-term health benefits of these behaviors. Improvement in medical conditions is also an important sign of long-term health benefits. Rapid weight loss is not pursued, for the implications on growth ad pubertal development and the risk of inducing eating disorders. Children and adolescents with severe obesity should be referred to a pediatric weight management center that has access to a multidisciplinary team with expertise in childhood obesity. This article provides pediatricians a comprehensive and evidence based update on treatment recommendations of severe obesity in children and adolescents.


2012 - Minimal incidence of neonatal/infancy onset diabetes in Italy is 1:90,000 live births. [Articolo su rivista]
Iafusco, D; Massa, O; Pasquino, B; Colombo, C; Iughetti, Lorenzo; Bizzarri, C; Mammì, C; Lo Presti, D; Suprani, T; Schiaffini, R; Nichols, Cg; Russo, L; Grasso, V; Meschi, F; Bonfanti, R; Brescianini, S; Barbetti, F.
abstract

Until early 2000, permanent and transient neonatal diabetes mellitus (NDM), defined as diabetes with onset within 6 weeks from birth that requires insulin therapy for at least 2 weeks, were considered exceedingly rare conditions, with a global incidence of 1:500,000-1:400,000 live births. The new definition of NDM recently adopted, that includes patients with diabetes onset within 6 months of age, has prompted studies that have set the incidence of the permanent form alone between 1:210,000 and 1:260,000 live births. Aim of the present work was to ascertain the incidence of NDM (i.e. permanent + transient form) in Italy for years 2005-2010. Patients referred to the Italian reference laboratory for NDM between years 2005 and 2010 and screened for mutations in common NDM genes (KCNJ11, ABCC8, and INS) and for uniparental isodisomy of chromosome 6 (UDP6) were reviewed. A questionnaire aimed at identifying NDM cases investigated in other laboratories was sent to 54 Italian reference centers for pediatric diabetes. Twenty-seven patients with NDM born between 2005 and 2010 were referred to the reference laboratory. In this group, a mutation of either KCNJ11, ABCC8 or INS was found in 18 patients, and a case with UDP6 was identified. Questionnaires revealed 4 additional cases with transient neonatal diabetes due to UDP6. Incidence of NDM was calculated at 1:90,000 (CI: 1:63,000-1:132,000) live births. Thus, with the definition currently in use, about 6 new cases with NDM are expected to be born in Italy each year.


2012 - Nipple trauma in infants? Bednar aphthae. [Articolo su rivista]
Tricarico, Antonella; Molteni, G.; Mattioli, F.; Guerra, A.; Mordini, B.; Presutti, Livio; Iughetti, Lorenzo
abstract

INTRODUCTION: Bednar aphthae are infected wounds caused by trauma, localized to the hard palate in infants. They do not require specific treatment because they regress spontaneously in a few days. They often remain undiagnosed; other times, because of the pain they caused, they may worsen the nursing.CASE REPORT: We describe the clinical case of a healthy infant of 2 months, fed with formula, who has 2 aphthous lesions in the oral cavity associated with irritability and inconsolable crying during feeding. We excluded the influence of infectious factors or underlying diseases. The hypothesis of a traumatic factor was supported by the anatomical features of aphthae and then confirmed by the gradual resolution of lesions after some advices on breastfeeding.CONCLUSIONS: Our intent is to provide a photographic record of Bednar aphthae, which are quite common but often misdiagnosed also because of lacking of photographic material. Improved knowledge of this condition helps physicians in the differential diagnosis of a traumatic condition that is not as unusual as it seems in newborns.


2012 - Obesity in patients with acute lymphoblastic leukemia in childhood. [Articolo su rivista]
Iughetti, Lorenzo; Bruzzi, Patrizia; Predieri, Barbara; Paolucci, Paolo
abstract

Acute lymphoblastic leukemia is the most common malignancy in childhood. Continuous progress in risk-adapted treatment for childhood acute lymphoblastic leukemia has secured 5-year event-free survival rates of approximately 80% and 8-year survival rates approaching 90%. Almost 75% of survivors, however, have a chronic health condition negatively impacting on cardiovascular morbidity and mortality. Obesity can be considered one of the most important health chronic conditions in the general population, with an increasing incidence in patients treated for childhood cancers and especially in acute lymphoblastic leukemia survivors who are, at the same time, more at risk of experiencing precocious cardiovascular and metabolic co-morbidities. The hypothalamic-pituitary axis damage secondary to cancer therapies (cranial irradiation and chemotherapy) or to primary tumor together with lifestyle modifications and genetic factors could affect long-term outcomes. Nevertheless, the etiology of obesity in acute lymphoblastic leukemia is not yet fully understood. The present review has the aim of summarizing the published data and examining the most accepted mechanisms and main predisposing factors related to weight gain in this particular population.


2012 - PARA-PARESI: UN RARO ESORDIO DI LINFOMA DI HODGKIN. [Abstract in Rivista]
Baroni, Lorenza; Fornaciari, Sara; Bigi, Elena; Codifava, Margherita; P., Bergonzini; A., Guerra; Iughetti, Lorenzo; Paolucci, Paolo
abstract

Il linfoma di Hodgkin (LH) è una patologia linfoproliferativa a cellule B, con peculiari caratteristiche cliniche, istologiche e immunofenotipiche. La patologia può diffondere dai linfonodi paravertebrali attraverso i forami intervertebrali in regione toracica o addominale causando compressione spinale. In casi rari può esordire con dolore, indebolimento degli arti inferiori e deficit sensitivi con successiva perdita del controllo degli sfinteri e para-paresi. Tale sintomatologia è più frequente nel decorso di malattia. Queste forme sono altamente resistenti alla chemioterapia.


2012 - POI: A Score to Modulate GH Treatment in Children with Prader-Willi Syndrome. [Articolo su rivista]
Salvatoni, A; Berini, J; Chiumello, G; Crinò, A; Di Candia, S; Gargantini, L; Grugni, G; Iughetti, Lorenzo; Luce, A; Musolino, G; Sogno Valin, P; Spica Russotto, V; Trifirò, G.
abstract

N.A.


2012 - Quasi cieco all'improvviso [Abstract in Rivista]
Pietrangiolillo, Zaira; Venturelli, Cristina; De Fanti, A.; Cimino, L.; D'Aquino, I.; Crisafi, A.; Monti, F.; Ruberto, C.; Graffagnino, A.; Iughetti, Lorenzo; Amarri, S.
abstract

La malattia di VKH è una coroidite stromale primaria bilaterale, causata da una reazione autoimmunitaria verso una proteina dei melanociti stromali, che evolve verso panuveite bilaterale con papillite, distacco di retina essudativo e uveite anteriore granulomatosa. La malattia oculare può associarsi a manifestazioni sistemiche extraoculari (infiammazione delle meningi, disturbi uditivi e alterazioni dell'apparato tegumentario).


2012 - The SHOX gene and the short stature. Roundtable on diagnosis and treatment of short stature due to SHOX haploinsufficiency: how genetics, radiology and anthropometry can help the pediatrician in the diagnostic process Padova (April 20th, 2011). [Relazione in Atti di Convegno]
De Sanctis, V; Tosetto, I; Iughetti, Lorenzo; Antoniazzi, F; Clementi, M; Toffolutti, T; Facchin, P; Monti, E; Pisanello, L; Tonini, G; Greggio, N. A.
abstract

The growth of the human body depends from a complex interaction between nutritional, environmental and hormonal factors and by a large number of different genes. One of these genes, short stature homeobox (SHOX), is believed to play a major role in growth. SHOX haploinsufficiency is associated with a wide spectrum of conditions, all characterized growth failure such as Leri-Weill dyschondrosteosis, Turner syndrome, short stature with subtle auxological and radiological findings and the so called "idiopathic short stature" (short stature with no specific findings other than growth failure). The document was prepared by a multidisciplinary team (paediatric endocrinologists, paediatrician, radiologist, geneticist and epidemiologist) to focus on the investigation of children with suspected SHOX- deficiency (SHOX-D) for an early identification and a correct diagnostic work - up of this genetic disorder. On the basis of a number of screening studies, SHOX-D appears to be a relatively frequent cause of short stature. The following recommendations were suggested by our multidisciplinary team: (i) a careful family history, measurements of body proportions and detection of any dysmorphic features are important for the suspect of a genetic disorder ,(ii)the presence of any combination of the following physical findings, such as reduced arm span/height ratio, increased sitting height/height ratio, above average BMI, Madelung deformity, cubitus valgus, short or bowed forearm, dislocation of the ulna at the elbow, or the appearance of muscular hypertrophy, should prompt the clinician to obtain a molecular analysis of the SHOX region, (iii) it is of practical importance to recognise early or mild signs of Madelung deformity on hand and wrist radiographs, (iv) growth hormone ,after stimulation test, is usually normal. However, treatment with rhGH may improve final adult height; the efficacy of treatment is similar to that observed in those treated for Turner syndrome.


2012 - Unusual osseous presentation of blastomycosis in an immigrant child: A challenge for European pediatricians [Articolo su rivista]
Codifava, Margherita; Guerra, A; Rossi, G; Paolucci, Paolo; Iughetti, Lorenzo
abstract

Blastomycosis, caused by the thermally dimorphic fungus Blastomyces dermatitidis is a systemic pyogranulomatous infection, endemic in United States and Canada, with few reported cases in Africa and Asia. It is uncommon among children and adolescents, ranging from 3% to 10%. Clinical features vary from asymptomatic spontaneously healing pneumonia, through acute or chronic pneumonia, to a malignant appearing lung mass. Blastomycosis can originate a "metastatic disease" in the skin, bones, genitourinary tract and central nervous system. Bone is the third most common site of blastomycotic lesions, after lung and skin. Bones may be involved in 14-60% of cases of blastomycosis. Direct visualization of single broadbased budding yeast with specific stains in sputum or tissue samples at microscopy is the primary method for diagnosis, while culture is timeconsuming and other methods are unreliable. CASE PRESENTATION: We report a case of severe osteoarticular Blastomycosis occurring in a 3-years-old presented to our Emergency Department with pain and swelling of the left knee, successfully treated with surgical curettage and antifungal therapy. To our knowledge this is the first case reported in Europe. CONCLUSIONS: Blastomycosis represents a challenge for European physicians, and it should be included in the differential diagnosis of unexplained infections in patients coming from endemic areas.


2012 - Usefulness of CGM with iPro2 in children with T1DM and correlations between Glucose Variability and metabolic control [Abstract in Rivista]
Zucchini, Stefano; Scipione, M; Predieri, Barbara; Iughetti, Lorenzo; Balsamo, C; Rollo, A; Bruzzi, Patrizia; Molinari, E; Di Stefano, P; Maltoni, Giulio
abstract

Objectives: Primary aim of the study was to evaluate the effect of a single iPro2 CGM on 3-months. HbA1c. Secondary aims were the feasibility of iPro2 monitoring and the evaluation of different metabolic and risk indexes. Methods: Seventy pts with T1DM (age 13.8 ± 4.6 years, T1DM duration 7.4 ± 3.6 years, HbA1c 8.4% ± 1.3) treated with three different insulin regimens (three inj of premix ins. n = 6, MDI n = 45, CSII n = 19) wore iPro2 for 6 days. iPro2 was applied in pts with HbA1c >7% (n.59) despite optimized therapy, or with recurrent hypoglycemia and HbA1c <7% (n.11). HbA1c was tested before and 3 months. after CGM data were used for glucose variability (GV) indexes calculation (CV, Conga, MAGE, MODD, AUC) and glycemic risk (GR) assessment (LBGI, HBGI, BGRI, J index, ADRR and BG Rate). LBGI and HBGI were also tested for correlation with baseline (BL) parameters (HbA1c, age, BMI, pubertal stage, disease duration, therapeutic regimen). Results: No pts reported significant side effects. Three-month HbA1c decreased to 8.0% ± 1.0 (P = 0.04). In the pts with HbA1c >7% (n.51) HbA1c decreased from 8.8% ± 1.2 to 8.3% ± 0.94 (P = 0.008), while in the pts with HbA1c <7% (n.12) was unchanged 6.5% ± 0.4 of 6.7% ± 0.4 (NS). HBGI and LBGI didn’t significantly correlate with any BL parameter both in the univariate and multivariate logistic regression analysis. GV indexes were evaluated in pts with HbA1c increasing (n = 23, from 7.6 ± 1.1 to 8.1 ± 1.2) and decreasing (n = 47, from 8.8 ± 1.3 to 7.9 ± 0.9) founding no differences. Furthermore no significant differences were found between the therapy groups in GV indexes. Conclusions: iPro2 is feasible in pediatric patients and was helpful in improving HbA1c especially in patients with suboptimal glicemic control. No significant correlation was found between BL characteristics of pts and GR indexes (HBGI and LBGI). Since no significant difference was found considering HbA1c increasing and decreasing trend, it is confirmed the independent value of GV indexes in the assessment of metabolic control.


2011 - Aldosterone synthase deficiency (ASD): two new italian cases with different presentation and diagnostic patterns [Abstract in Rivista]
A., Balsamo; D., Rinaldini; F., Riepe; I., Bettocchi; P., Pirazzoli; Iughetti, Lorenzo; M. F., Roversi; A., Cicognani
abstract

The abstract shows two new italian cases with different presentation and diagnostic patternscaused by Aldosterone synthase deficiency (ASD):


2011 - Allopregnanolone Levels Decrease after Gonadotropin Releasing Hormone Analogue Stimulation Test in Girls with Central Precocious Puberty. [Articolo su rivista]
Predieri, Barbara; Luisi, S; Casarosa, E; Farinelli, E; Antoniazzi, F; Wasniewska, M; Bernasconi, S; Petraglia, F; Iughetti, Lorenzo
abstract

Allopregnanolone (AP), neuroactive steroid secreted by brain, adrenals, and gonads, is a hormone that seems to play a role in the development of precocious puberty, as demonstrated by its high baseline levels found in girls with central precocious puberty (CPP). AP concentrations significantly increase after gonadotropin-releasing hormone (GnRH) and adrenocorticotropin hormone (ACTH) stimulation test suggesting both its ovarian and adrenal production. Aim of this study was to evaluate AP concentrations after GnRH and gonadotropin-releasing hormone agonist analogue (GnRHa) stimulation test in girls with CPP to better establish its secretion source. Gonodotropins and steroid hormones were evaluated in different days after GnRH and triptorelin (TRIP) stimulation test in 12 CPP girls. After GnRH stimulation luteinizing hormone (LH), follicle-stimulating hormone (FSH), and AP concentrations significantly increased (P &lt; 0.05). After TRIP administration LH, FSH, estradiol and 17 hydroxy-progesterone levels significantly increased (P &lt; 0.05), while AP concentrations significantly decreased (1.10 ± 0.26 vs. 0.89 ± 0.29 nmol/l; P = 0.001). The different response of AP to GnRH and GnRHa might reflect the agonist and antagonist action exerted by these secretagogues. Our data suggest the prevalent gonadal AP production in CPP subjects and the usefulness of its measurement in the diagnosis of CPP.


2011 - Combined characterization of a pituitary adenoma and a subcutaneous lipoma in a MEN1 patient with a whole gene deletion [Articolo su rivista]
D., Rusconi; E., Valtorta; O., Rodeschini; D., Giardino; Iughetti, Lorenzo; Predieri, Barbara; M., Losa; L., Larizza; P., Finelli
abstract

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary disorder associated with mutations of the MEN1 gene, which is characterized by combined tumors of the parathyroid glands, pancreatic islet cells, and the anterior pituitary. A significant number of patients with the clinical features of MEN1, however, do not show MEN1 mutations upon direct sequencing. We describe a young woman who fulfilled the clinical and biochemical criteria for MEN1 syndrome, but DNA sequencing did not indicate any MEN1 mutations. She developed a prolactin-secreting pituitary macroadenoma, primary hyperparathyroidism with parathyroid hyperplasia, pancreatic lesions, and two subcutaneous lipomas. Array comparative genomic hybridization (aCGH) analysis of peripheral blood DNA revealed a heterozygous germline deletion at 11q13.1 that spanned at least 22.23 kilobases and contained the entire MEN1 gene. Integrated aCGH and cytogenetic analyses of the adenoma and lipoma tissues revealed somatic inactivation of the wild-type MEN1 allele by different routes: the second hit of MEN1 recessive oncogenesis leading to adenoma implied a loss of heterozygosity, whereas a balanced translocation deleting the wild-type MEN1 allele primed the lipoma development. These findings show that aCGH is a valuable means of optimizing genetic testing in MEN1 patients which complements other technologic approaches to elucidating the pathologic mechanisms of MEN1 tumors.


2011 - High levels of serum perfluorinated compounds in children and adolescents with endocrine autoimmune disease [Abstract in Rivista]
Iughetti, Lorenzo; Predieri, Barbara; Guerranti, Cristiana; Bruzzi, Patrizia; Madeo, Simona Filomena; Patianna, Viviana D; Catellani, Chiara; Fanello, El; Perra, G; Focardi, S. e.
abstract

Background: Impairments of endocrine system may be associated with exposure to certain chemical compounds. Much attention has recently focused on interference with thyroid function in relation to exposure to endocrine disruptors chemicals among which perfluorinated compounds (PFCs) are considered a priority research issue. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are widely diffused since used in the productions of polymers, additives, adhesives, cosmetics, insecticides and many other uses. PFCs are characterized by a high potential to bioaccumulate, by binding proteins, aspect that allows transmission of contamination through food chains and retention in the body, once assumed. Objective: Aim of this study is to assess PFCs concentrations in children and adolescents with type 1 diabetes (T1DM) compared to healthy controls. Methods: Forty-four children and adolescents were recruited and subdivided in the following groups: (1) twenty-five subjects (6.11 ± 3.33 years.) with T1DM and (2) nineteen healthy controls matched for age and gender. Blood samples to assay PFCs were collected and stored few days after T1DM was diagnosed. PFOS and PFOA have been extracted following an ion-pairing extraction procedure and determined by HPLC-ESI-MS. Nonparametric statistical analysis was performed. Results: PFOS concentrations resulted significantly higher in T1DM patients respect to controls (1.53 ± 1.50 vs. 0.55 ± 0.15 ng/ml, respectively; P = 0.0001, Mann–Whitney U-test). No difference was found in PFOA levels (0.53 ± 0.09 vs. 0.50 ± 0.06 ng/ml, respectively; P = 0.148, Mann–Whitney Utest). Conclusions: Our data suggests that higher serum levels of PFOS may be considered as a biomarker of exposure and susceptibility to develop TIDM. Further studies are necessary to better understand the role of this and other chemical compound as triggers of autoimmune endocrine diseases during childhood.


2011 - High levels of serum perfluorinated compounds in children with endocrine autoimmune disease. [Abstract in Rivista]
Iughetti, Lorenzo; C., Guerranti; Predieri, Barbara; Bonetti, Annalisa; S., Madeo; Patianna, VIVIANA DORA; S., Luisi; E. L., Fanello; G., Perra; S., Focardi
abstract

with thyroid function in relation to exposure to endocrine disruptors chemicals among which perfluorinated compounds (PFCs) are considered a priority research issue.Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are widely diffused since used in the productions of polymers, additives, adhesives, cosmetics,insecticides and many other uses. PFCs are characterized by a high potential to bioaccumulate, by binding proteins, aspect that allows transmission of contaminationthrough food chains and retention in the body, once assumed.Objective and hypotheses: Aim of this study is to assess PFCs concentrations in children with autoimmune endocrine diseases such as type 1 diabetes (T1DM) andthyroiditis (Tr).Methods: Sixtythreechildren were recruited and subdivided in the following three groups: A) twentyfivesubjects (6.11±3.33 yr.) with T1DM, B) nineteen subjects(6.57±2.69 yr.) with Tr, and C) nineteen healthy controls matched for age and gender. Blood samples to assay PFCs were collected and stored few day after T1DM or Trwere diagnosed. PFOS and PFOA have been extracted following an ionpairingextraction procedure and determined by HPLCESIMS.Nonparametric statistical analysiswas performed.Results: PFOS concentrations resulted significantly higher in both T1DM and Tr patients respect to controls (1.53±1.50 and 1.21±1.57 vs. 0.55±0.15 ng/ml, respectively;χ2 =8.12; KruskalWallistest=14.5; p=0.017) (Figure). No difference was found in PFOA levels.Conclusions:


2011 - Metabolic syndrome in children with Prader-Willi syndrome: the effect of obesity. [Articolo su rivista]
Brambilla, P; Crinò, A; Bedogni, G; Bosio, L; Cappa, M; Corrias, A; Delvecchio, M; Di Candia, S; Gargantini, L; Grechi, E; Iughetti, Lorenzo; Mussa, A; Ragusa, L; Sacco, M; Salvatoni, A; Chiumello, G; Grugni, G.
abstract

BACKGROUND AND AIMS: Prader-Willi syndrome (PWS), the most frequent syndromic obesity, is associated with elevated morbidity and mortality in pediatric and adult ages. In PWS, the presence of metabolic syndrome (MS) has not yet been established. The aim of the study was to estimate the frequency of MS and its components in pediatric subjects according to obesity status.METHODS AND RESULTS: A cross-sectional study was performed in 109 PWS children aged 2-18 years (50 obese and 59 non-obese) and in 96 simple obese controls matched for age, gender, and also for BMI with obese PWS. Obesity was defined when SDS-BMI was &gt;2. Non-obese PWS showed significantly lower frequency of hypertension (12%) than obese PWS (32%) and obese controls (35%)(p=0.003). The same was observed for low HDL-cholesterol (3% vs 18% and 24%, p=0.001) and high triglycerides (7% vs 23% and 16%, p=0.026). Frequency of altered glucose metabolism was not different among groups (2% vs 10% and 5%), but type 2 diabetes (four cases) was present only in obese PWS. Non-obese PWS showed lower insulin and HOMA-index respect to obese PWS and obese controls (p ≤ 0.017). Overall MS frequency in PWS was 7.3%. None of the non-obese PWS showed MS compared with 16% of obese PWS and controls (p&lt;0.001). When obesity was excluded from the analysis, a significantly lower frequency for clustering of ≥ 2 factors was still found in non-obese PWS (p=0.035).CONCLUSION: Non-obese PWS showed low frequency of MS and its components, while that observed in obese PWS was very close to those of obese controls, suggesting the crucial role of obesity status. Prevention of obesity onset remains the most important goal of PWS treatment. Early identification of MS could be helpful to improve morbidity and mortality in such patients.


2011 - Non-invasive methods can predict oesophageal varices in patients with biliary atresia after a Kasai procedure. [Articolo su rivista]
Colecchia, A; Di Biase, Ar; Scaioli, E; Predieri, Barbara; Iughetti, Lorenzo; Reggiani, Ml; Montrone, L; Ceccarelli, Pl; Vestito, A; Viola, L; Paolucci, Paolo; Festi, D.
abstract

BACKGROUND: After a Kasai procedure, 70% of patients with biliary atresia develop chronic liver disease with portal hypertension and oesophageal varices. AIMS: To investigate the role of new non-invasive parameters in predicting the presence of varices in patients with biliary atresia after a Kasai procedure and to identify the cut-off values of these parameters in predicting the presence of varices. METHODS: 31 patients with biliary atresia who had undergone a Kasai portoenterostomy were studied. Clinical, biochemical and abdominal ultrasound examination, liver stiffness measurement (LSM), LSM-spleen diameter to platelet ratio score (LSPS) and upper digestive endoscopy were performed. RESULTS: 15 (47%) patients had oesophageal varices (Group A) and 16 had no varices (Group B). Median values of LSM (kPa) and LSPS were significantly higher in Group A than in Group B (LSM: 17.0 vs. 7.5, respectively; p=0.0001; LSPS: 19.62 vs. 2.94, respectively; p=0.0001). The optimal cut-offs for predicting oesophageal varices were: LSM>10.6 kPa (sensitivity: 87%, specificity: 87.5%, PPV: 87%, NPV: 87.5%, and AUC: 0.92) and LSPS ≥9.2 (sensitivity: 91%, specificity: 92%, PPV: 91%, NPV: 92%, and AUC: 0.96). CONCLUSIONS: Non-invasive methods can predict the presence of oesophageal varices in patients with biliary atresia; the sequential use of two non-invasive methods improves accuracy.


2011 - Obesity and craniopharyngioma. [Articolo su rivista]
Iughetti, Lorenzo; Bruzzi, Patrizia
abstract

An epidemic of pediatric obesity has occurred across the world in recent years. There are subgroups within the population at high-risk of becoming obese and especially of having experience of precocious cardiovascular and metabolic co-morbidities of obesity. One of these subgroups comprises patients treated for childhood cancers and namely survivors of craniopharyngioma. The high incidence of obesity in this group makes these patients an important disease model to better understand the metabolic disturbances and the mechanisms of weight gain among cancer survivors. The hypothalamic-pituitary axis damage secondary to cancer therapies or to primary tumor location affect long-term outcomes. Nevertheless, the aetiology of obesity in craniopharyngioma is not yet fully understood. The present review has the aim of summarizing the published data and examining the most accepted mechanisms and main predisposing factors related to weight gain in this particular population.


2011 - Permanent diabetes during the first year of life: multiple gene screening in 54 patients. [Articolo su rivista]
Russo, L; Iafusco, D; Brescianini, S; Nocerino, V; Bizzarri, C; Toni, S; Cerutti, F; Monciotti, C; Pesavento, R; Iughetti, Lorenzo; Bernardini, L; Bonfanti, R; Gargantini, L; Vanelli, M; Aguilar Bryan, L; Stazi, Ma; Grasso, V; Colombo, C; Barbetti, F.
abstract

AIMS/HYPOTHESIS: The aim of this study was to investigate the genetic aetiology of permanent diabetes mellitus with onset in the first 12 months of age. METHODS: We studied 46 probands with permanent, insulin-requiring diabetes with onset within the first 6 months of life (permanent neonatal diabetes mellitus [PNDM]/monogenic diabetes of infancy [MDI]) (group 1) and eight participants with diabetes diagnosed between 7 and 12 months of age (group 2). KCNJ11, INS and ABCC8 genes were sequentially sequenced in all patients. For those who were negative in the initial screening, we examined ERN1, CHGA, CHGB and NKX6-1 genes and, in selected probands, CACNA1C, GCK, FOXP3, NEUROG3 and CDK4. The incidence rate for PNDM/MDI was calculated using a database of Italian patients collected from 1995 to 2009. RESULTS: In group 1 we found mutations in KCNJ11, INS and ABCC8 genes in 23 (50%), 9 (19.5%) and 4 (8.6%) patients respectively, and a single homozygous mutation in GCK (2.1%). In group 2, we identified one incidence of a KCNJ11 mutation. No genetic defects were detected in other loci. The incidence rate of PNDM/MDI in Italy is estimated to be 1:210,287. CONCLUSIONS/INTERPRETATION: Genetic mutations were identified in ~75% of non-consanguineous probands with PNDM/MDI, using sequential screening of KCNJ11, INS and ABCC8 genes in infants diagnosed within the first 6 months of age. This percentage decreased to 12% in those with diabetes diagnosed between 7 and 12 months. Patients belonging to the latter group may either carry mutations in genes different from those commonly found in PNDM/MDI or have developed an early-onset form of autoimmune diabetes.


2011 - Pharmacological treatment of obesity in children and adolescents: present and future. [Articolo su rivista]
Iughetti, Lorenzo; China, M; Berri, R; Predieri, Barbara
abstract

The prevalence of overweight and obesity is increasing in children and adolescents worldwide raising the question on the approach to this condition because of the potential morbidity, mortality, and economic tolls. Dietetic and behavioral treatments alone have only limited success; consequently, discussion on strategies for treating childhood and adolescent obesity has been promoted. Considering that our knowledge on the physiological systems regulating food intake and body weight is considerably increased, many studies have underlined the scientific and clinical relevance of potential treatments based on management of peripheral or central neuropeptides signals by drugs. In this paper, we analyze the data on the currently approved obesity pharmacological treatment suggesting the new potential drugs.


2011 - Plasma brain-derived neurotrophic factor concentrations in children and adolescents. [Articolo su rivista]
Iughetti, Lorenzo; Casarosa, E; Predieri, Barbara; Patianna, V; Luisi, S.
abstract

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a mediator of neuronal plasticity influencing learning, memory and cognitive behavior. The aim of this study is to assess plasma BDNF variations according to pubertal status. METHODS: A total of 110 subjects were included in the study. Blood samples were collected after overnight fasting. Plasma BDNF concentrations were measured by enzyme-linked immunosorbent assay. Gonadotrophins, sex steroids, and IGF-1 were also assessed.RESULTS: BDNF was positively correlated with platelet count and negatively associated with both BMI and age. BDNF levels in pubertal males were significantly lower than prepubertal males and both prepubertal and pubertal females. CONCLUSIONS: Plasma BDNF levels seem to be influenced by hormonal status. We demonstrate that parameters such as age or gender have a specific impact on stored and circulating BDNF blood levels and platelets remain the most important predictor of their concentration. Further studies are necessary to better understand the role of this neurotrophin in pubertal development.


2011 - Potential celiac disease in type 1 diabetes: A multicenter study [Articolo su rivista]
Franzese, A.; Iafusco, D.; Spadaro, R.; Cavaliere, O.; Prisco, F.; Auricchio, R.; Troncone, R.; Valerio, G.; Lera, R.; Fontana, F.; Cherubini, V.; Biagioni, M.; Pasquino, B.; Gallo, F.; Suprani, T.; Tumini, S.; Lazzaro, N.; Toni, S.; D'Annunzio, G.; Emmanuele, V.; Bruzzese, M.; Lombardo, F.; Bonfanti, R.; Tronconi, G. M.; Iughetti, L.; Monciotti, C.; Cardella, F.; Chiari, G.; Vanelli, M.; Calcaterra, V.; Federico, G.; Crino, A.; Cappa, M.; Patera, I.; Negro, I.; Delvecchio, M.; Rabbone, I.; Guerraggio, L.; Salvatoni, A.; Costantini, C.; Pinelli, L.
abstract

Aims: To describe the prevalence of potential celiac disease (pot-CD) in young patients with type 1 diabetes mellitus (T1DM) and characterize their clinical features. Methods: This cross-sectional multicenter study involved 8717 T1DM patients from 31 Italian centers. Information was collected on the total number of T1DM patients, CD patients and pot-CD patients. The following data were collected on pot-CD patients: gender, age at T1DM diagnosis, age at the first CD serological positivity, presence of CD-related symptoms, presence of other autoimmune disorders and treatment with gluten free diet (GFD). One thousand-three-hundred-sixty-one patients who were positive for CD serology were the control group. Results: CD serological positivity was found in 7.2% T1DM patients. Prevalence of pot-CD was 12.2% (n = 77) among CD positive patients: symptoms were present in 12/77; a third autoimmune disorder was found in 15 patients. Prevalence of pot-CD in the control population was 8.4% (n = 114; p = 0.005). No difference was found with regard to clinical features. Only few symptomatic patients were on GFD both in T1DM and control patients. Conclusions: A higher prevalence of pot-CD was found in T1DM patients, that may be ascribed to the routine screening, although the influence of genetic factors cannot be excluded. © 2010.


2011 - Quality of life in children and adolescents with type 1 diabetes and coeliac disease. [Abstract in Rivista]
Pugliese, Marisa; Predieri, Barbara; Zani, Fabiana; Guerzoni, Maria Elena; Bruzzi, Patrizia; Vellani, Giulia; Di Biase, Anna Rita; Bonetti, Annalisa; Madeo, Simona Filomena; Iughetti, Lorenzo
abstract

Health-related quality of life (HRQOL) is an important health outcome and a well-know indicator of the long-term consequences of chronic diseases that affect the quality of life (QOL). Aim of our study was to investigate general and HRQOL of children with type 1 diabetes (T1DM) and subjects with coeliac disease (CD) compared to healthy controls. We studied 101 outpatients: 35 children with T1DM (12.8 ± 2.85 years, duration of T1DM 60.5 ± 33.4 months), 32 subjects with CD (9.60 ± 2.61 year, duration of CD 52.0 ± 47.9 months), and 34 controls children matched for age and sex. All subjects were assed using the Paediatric Quality of Life Inventory (PedsQL) Generic Core Scales to measure HRQOL with 23 items included in 4 scales. T1DM patients showed a satisfactory metabolic control HbA1c (8.06 ± 0.75%). Twenty-one out of 32 CD subjects showed a strict dietetic control. We demonstrated that social functioning (fx), school (fx), psychosocial health (fx), and total scale were significantly different between groups; the major concern was related to emotional (fx). Our results demonstrate that children and adolescents with chronic disease, despite a good adherence to therapy, have impairment in psychosocial health (fx). Our data disagree with common opinion that children with CD have a better adaptation and functioning. These findings contribute significant information on the effects of pediatric chronic conditions on generic QOL from the perspectives of children. It is conceivable that an immediate multidisciplinary approach to patients with T1DM can be responsible for this differences.


2011 - Quando il glutine colpisce al cuore [Abstract in Atti di Convegno]
Lucaccioni, Laura; Bussetti, Chiara; Maria Salvini, Anna; Bergonzini, Patrizia; Pancaldi, Elena; Guerra, Azzurra; Iughetti, Lorenzo; Paolucci, Paolo
abstract

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2011 - Recurrent pneumococcal meningitis in a child with transethmoidal encephalocele: a case report and review of literature. [Articolo su rivista]
Cantatore, S; Crisafi, A; Guaraldi, N; Pancaldi, Me; Iughetti, Lorenzo
abstract

Bacterial meningitis is a life-threatening infection with a low recurrence rate. However, this possibility has always to be considered and avoided. This case report concerns a 5-year-old girl who was admitted in our Emergency Pediatric Unit for symptoms of bacterial meningitis and signs of disseminated intra-vascular coagulopathy. After a successful treatment the girl was discharged in good health. She was admitted to our hospital after one year with the same symptoms of meningitis. Laboratory examinations confirm the admittance suspect. An accurate research allowed to find out immunological deficiencies and showed an occult malformation, transethmoidal encephalocele, responsible for the recurrent meningitis. The present case suggests that the opportunity to perform an accurate cerebral imaging study (with special attention to the ethmoidal region and inner ear) in all cases of meningitis to detect occult anatomical alterations, thus preventing infectious recurrence, should always be taken into account.


2011 - Ten-years longitudinal study of thyroid function in children with Down syndrome. [Abstract in Rivista]
Predieri, Barbara; L., Garavelli; A., Bonetti; Vellani, Giulia; F., Predieri; C., Cattelani; S., Madeo; Iughetti, Lorenzo
abstract

Background: Children with Down syndrome (DS) show an increased prevalence of thyroid disease when compared with the general population. The risk for thyroid dysfunction rises with age. A yearly thyroid screening was suggested in the guidelines of the American Academy of Pediatrics for the health supervision of children withDS.Objective and hypotheses: The aim of our investigation is to longitudinally study the thyroid function in children with DS in order to identify the prevalence of thyroid pathology throughout development.Methods: Thyroid function tests were yearly carried out on 120 children with DS, all followed from birth to 10 years of age. There were 65 boys and 55 girls. Subjects were annually classified according to thyroid function as: normal, congenital hypothyroidism (C-HT), hypothyroidism (HT - TSH >10 mcIU/ml and low FT4), subclinical hypothyroidism (S-HT - TSH between 5 and 10 mcIU/ml and normal FT4), hyperthyroidism (HyperT).Results: In our study population the prevalence of normal thyroid function significantly decreased from 90.8% to 41.7% throughout 10-years follow-up. Therefore, the prevalence of thyroid dysfunctions increased, in particular the HT ones. The abnormal findings were almost equally distributed between the genders.Conclusions: More than half of the children with DS in our study developed thyroid dysfunctions. Our results confirm that DS patients, especially those with normal thyroid function and subclinical hypothyroidism, should be carefully followed annually to precociously identify the appearance of thyroid pathology and to begin an adequate hormonal treatment.presentation)


2011 - Un caso di neurofibromatosi ad esordio molto precoce. [Abstract in Atti di Convegno]
Bussetti, Chiara; Salvini, Annamaria; Lucaccioni, Laura; P., Bergonzini; A., Guerra; M., Trebbi; Presutti, Livio; Iughetti, Lorenzo; Paolucci, Paolo
abstract

non disponibile


2011 - Uno strano caso di alcalosi metabolica in paziente con acidosi tubulare renale [Abstract in Atti di Convegno]
Lucaccioni, Laura; Dozza, Alessandra; Cantatore, Sante L.; Rossi, Cecilia; Iughetti, Lorenzo
abstract

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2010 - Afasia talamica post-encefalitica [Abstract in Rivista]
S., Cipolli; Frassoldati, Rossella; C., Rossi; G., Vivi; C., Molinari; V., Cioni; S., Leoni; A., Guerra; Iughetti, Lorenzo
abstract

Le sindromi talamiche si presentano nell’adulto come quadri lesionali specifici legati all’insulto ischemico. In letteratura sono segnalati pochi casi di afasia talamica successivi a infarti ischemici nel bambino. Il caso in esame riconosce punti di somiglianza con i quadri più conclamati dell’adulto e, insieme, caratteristiche di peculiarità correlate alla fase evolutiva del linguaggio, costituite principalmente da ritardo dell’acquisizione di nuovi vocaboli e importante disturbo fonologico. Per il ritardo di linguaggio la bambina è stata presa in carico dal Servizio di NPI del territorio per programma di riabilitazione logopedica.


2010 - Age-period-cohort analysis of 1990-2003 incidence time trends of childhood diabetes in Italy: The RIDI study [Articolo su rivista]
Bruno, G; Maule, M; Merletti, F; Novelli, G; Falorni, A; Iannilli, A; Iughetti, Lorenzo; Altobelli, E; D'Annunzio, G; Piffer, S; Pozzilli, P; Iafusco, D; Songini, M; Roncarolo, F; Toni, S; Carle, F; Cherubini, V; Cerutti, F; Novelli, G; Franchini, S; Bianchi, L; Lorini, R; Minuto, N; Sacco, S; Ramondetti, F; Predieri, Barbara; Reali, S; Medici, A; Biagioni, M; Gesuita, R; Santeusanio, F; De Giorgi, G; Visalli, N; Bizzarri, C; Chiarelli, F; Tumini, S; Prisco, F; Confetto, S; Frongia, P; Marinaro, A.
abstract

OBJECTIVE - To investigate age-period-cohort effects on the temporal trend of type 1 diabetes in children age 0-14 years in Italian registries. RESEARCH DESIGN AND METHODS - This report is based on 5,180 incident cases in the period 1990-2003 from the Registry for Type 1 Diabetes Mellitus in Italy (RIDI). Multilevel (random intercept) Poisson regression models were used to model the effects of sex, age, calendar time, and birth cohorts on temporal trends, taking into account the registry-level variance component. RESULTS - The incidence rate was 12.26 per 100,000 personyears and significantly higher in boys (13.13 [95% CI 12.66-13.62]) than in girls (11.35 [10.90-11.82]). Large geographical variations in incidence within Italy were evident; incidence was highest in Sardinia, intermediate in Central-Southern Italy, and high in Northern Italy, particularly in the Trento Province, where the incidence rate was 18.67 per 100,000 person-years. An increasing temporal trend was evident (2.94% per year [95% CI 2.22-3.67]). With respect to the calendar period 1990-1992, the incidence rates increased linearly by 15, 27, 35, and 40% in the following time periods (P for trend &lt; 0.001). With respect to the 1987-1993 birth cohort, the incidence rate ratio increased approximately linearly from 0.63 (95% CI 0.54-0.73) in the 1975-1981 cohort to 1.38 (1.06-1.80) in the 1999-2003 cohort. The best model, however, included sex, age, and a linear time trend (drift). CONCLUSIONS - Large geographical variations and an increasing temporal trend in diabetes incidence are evident among type 1 diabetic children in Italy. Age-period-cohort analysis shows that the variation over time has a linear component that cannot be ascribed to either the calendar period or the birth cohort.


2010 - Anti-pituitary antibodies in children with newly diagnosed celiac disease: a novel finding contributing to linear-growth impairment. [Articolo su rivista]
Delvecchio, M; De Bellis, A; Francavilla, R; Rutigliano, V; Predieri, Barbara; Indrio, F; De Venuto, D; Sinisi, Aa; Bizzarro, A; Bellastella, A; Iughetti, Lorenzo; Cavallo, L.
abstract

Objective The possible autoimmune involvement of the pituitary gland in patients with celiac disease (CD) was suggested, but demonstrated only in few patients on gluten free diet. We aimed to assess prevalence and clinical meaning of antipituitary antibodies (APA) in children and adolescents with newly diagnosed CD.Design Cross-sectional.Setting Inpatient Clinic of University Hospital.Patients 119 celiac patients (0.9 – 15.8 years old).Intervention and main outcome measures Auxological data, height, weight and body mass index (BMI), were recorded, insulin-like growth factor-1 (IGF-1) and APA assayed. APA were assayed also in 98 sex- and age-matched controls. Results APA were detected in 50 patients (42.0%), 15 of them with high titre (30%) and 35 with low titre (70%), and in 2 control subjects at low titre (2%) (p < 0.001). IGF-1 was higher in patients with negative than with low titre (p = 0.02) or high titre APA (p = 0.03). Height was more reduced in hig titre APA patients than in negative (p < 0.01). Height was positively correlated with IGF-1 (p < 0.01) and negatively with chronological age (p = 0.001). IGF-1 was positively correlated with BMI (p < 0.001). The regression analysis showed the rank order 1 for chronological age and 2 for IGF-1 for height prediction.Conclusions Our paper shows a remarkable prevalence of positive APA in newly diagnosed CD patients. High APA titres are associated with height impairment, likely mediated by a reduction of IGF-1 suggesting that autoimmune pituitary process could induce a linear growth impairment.


2010 - Diagnosi prenatale di sclerosi tuberosa [Abstract in Rivista]
C., Rossi; Frassoldati, Rossella; V., Fiorini; I., Guidotti; S., Cipolli; A., Guerra; Iughetti, Lorenzo
abstract

La sclerosi tuberosa è una malattia genetica multisistemica che causa lesioni circoscritte, non invasive, in vari organi (SNC, cuore, reni, fegato, occhi, cute...); l’incidenza è pari a 1/6000 nati. La trasmissione è autosomica dominante, ma 2/3 dei pazienti presentano mutazioni sporadiche1. I geni coinvolti sono TSC1 (9q34-amartina, circa 45% dei casi) e TSC2 (16p13.3-tuberina, circa il 55% dei casi)2. Esistono criteri di diagnosi maggiori e minori: la diagnosi si effettua quando sono presenti 2 criteri maggiori oppure uno maggiore associato a due minori. La diagnosi può essere prenatale, tramite ecografia e RMN fetali che sono in grado di mostrare lesioni cardiache e cerebrali, permettendo intervento e trattamento precoci


2010 - Diagnostic features of thyroid nodules in pediatrics. [Articolo su rivista]
Corrias, A; Mussa, A; Baronio, F; Arrigo, T; Salerno, M; Segni, M; Vigone, Mc; Gastaldi, R; Zirilli, G; Tuli, G; Beccaria, L; Iughetti, Lorenzo; Einaudi, S; Weber, G; De Luca, F; Cassio, A.
abstract

OBJECTIVE: To investigate a cohort of pediatric patients with thyroid nodules, defining histotype frequency and differences between subjects with hyperthyroidism and euthyroidism and benign and malignant nodules. DESIGN:Retrospective cohort. SETTING: Consecutive cases from 9 Italian pediatric endocrinology centers for the last 10 years. Patients One hundred twenty pediatric patients with thyroid nodules. Intervention Doppler ultrasonography was performed in 71 subjects; scintiscan, in 56; fine-needle aspiration biopsy in 104; and 63 underwent surgery. MAIN OUTCOME MEASURES: The differences in clinical, laboratory, and ultrasonographic data between patients with hyperthyroidism and euthyroidism and malignant and benign nodules were evaluated. RESULTS: One hundred fourteen patients had euthyroidism and 6, hyperthyroidism. The latter had more compressive signs (P=.003), greater nodule diameter (P=.02), intranodular vascularization pattern (P=.01), and increased scintiscan uptake (P<.001). Fine-needle aspiration biopsy disclosed benign lesions in 77 cases, malignant lesions in 19, and "suspicious" lesions in 8. Histologic examination disclosed 1 Hurthle cell and 5 follicular adenomas in patients with hyperthyroidism, whereas in patients with euthyroidism, 33 hyperplasic nodules, 19 carcinomas (14 papillary, 3 follicular, and 2 medullary), 3 follicular and 1 Hurthle cell adenoma, and 1 teratoma were detected. Nine patients had enhanced scintiscan uptake. Among the patients with euthyroidism, malignancies more frequently had palpable lymph nodes (P<.001), compressive signs (P=.004), microcalcifications (P<.001), intranodular vascularization (P=.01), and lymph node alterations (P<.001).CONCLUSIONS: The diagnosis of pediatric thyroid nodules should be based on a stepwise evaluation that includes clinical, laboratory, and radiographic modalities. While laboratory assessments establish thyroid function, ultrasonographic imaging identifies clinically unapparent nodules and provides detailed nodule characterization for suspected malignant lesions. Scintiscan in patients with hyperthyroidism and fine-needle aspiration biopsy in patients with euthyroidism represent the next logical step.


2010 - Evaluation and management of hyperlipidemia in children and adolescents. [Articolo su rivista]
Iughetti, Lorenzo; Bruzzi, P; Predieri, Barbara
abstract

Purpose of review. To review the recent findings on evaluation and management of dyslipidemia in childhood and adolescence, giving a critical view on new therapeutic approaches.Recent findings. In 2008, the American Academy of Pediatric released an updated policy statement recommending more frequent screening to detect dyslipidemia in childhood and the first-line use of statins in children with dyslipidemia who did not respond to lifestyleintervention and who were more than 8 years of age. These recommendations have caused a lot of controversy within the medical community and media. This debate is also sharpened by the fact that only few trials have investigated the long-term efficacy of statins on prevention of adult cardiovascular disease, their application indyslipidemias other than familial hypercholesterolemia and the use of new pharmacological tools.The purpose of our paper could not be achieved clearly without a review of the physiology of cholesterol metabolism together with an analysis of causes of primary and secondary dyslipidemia affecting children. Moreover, recent knowledge on lipid lowering therapy is reviewed.


2010 - Growth and nutritional evaluation in children with chronic liver disease (CLD) before and after liver transplantation [Abstract in Rivista]
Predieri, Barbara; Di Biase, A. R.; Berri, R.; Bruzzi, Patrizia; Colecchia, A.; Iughetti, Lorenzo
abstract

Acute or final hepatic insufficiency needs to be treated with hepatic transplantation. It represents an important cause of growth retardation mainly due to decrease of daily caloric intake and macro-/micronutrient adsorption and alteration of hepatic metabolism. Sometimes nutritional supplementation may be necessary. Aim of this study is to evaluate growth and nutritional status in children with hepatic insufficiency before and after hepatic transplantation.Ten children (4 boys and 6 girls; 3-13 years; 8 biliary atresy, 1 type I tyrosinemia, 1 Alagille’s Syndrome) were included in the study. Height, weight, and laboratory (albumin, hepatic and biliary index, lipids profile, coagulation) data were detected before, after 1, and 3 year hepatic transplantation. Insulin-like growth factor 1 (IGF-1), IGF-binding protein 3 (IGF-BP3), vitamin B12, and folic acid were measured only at the last visit. Parametric statistical analysis was performed. The auxological and laboratory characteristics of the patients are reported in the Table (p<0.05; *1 year vs. before; **3 years vs. both before and 1 year). Basal growth parameters were slightly compromised. Weight and BMI z-score significantly increased already 1 year after hepatic transplantation, resulting within normal range also at 3 years, while height z-score was significantly improved only after 3 years. Albumin levels resulted slightly impair before transplantation and significantly increase at the last control. A significant progressive decreased of bilirubin, biliary acid, alkaline phosphatase, and transaminase values was found after 1 and 3 years, finally resulting in the normal range. No other significant change was demonstrated for laboratory data. At the last evaluation nutritional and growth index (IGF-1 and IGF-BP3) were within normal range for age and sex. Our results confirm that a correct diet, sometimes supported by enteral nutrition, make it possible to obtain a satisfactory nutritional status before hepatic transplantation. This approach allows a more rapid improvement of growth already 1 year after surgery. IGF-1 levels may be considered an useful tool to evaluate clinical and nutritional status of these patients.


2010 - Growth Hormone Therapy in Patients with Short Stature Homebox-Gene (SHOX) deficiency [Articolo su rivista]
Iughetti, Lorenzo; S., Madeo; Predieri, Barbara
abstract

Short stature homeobox (SHOX) gene is located in the pseudoautosomal region 1 on the distal end of the X and Y chromosomes at Xp22.3 and Yp11.3. The haploinsufficiency of SHOX is correlated with short stature, Leri-Weill dyschondrosteosis, and Langer mesomelic dysplasia. Subjects with Turner syndrome (TS) present a SHOX haploinsufficiency that appears to be substantially responsible for their short stature. Several studies have shown a positive response to GH therapy in patients with TS. Short children with SHOX haploinsufficiency do not spontaneously catch up to attain a normal final height. Considering the positive effects obtained in patients with TS, GH therapy has been proposed for short stature due to isolated SHOX haploinsufficiency. The aim of this paper is to summarize the current data on GH administration in patients with SHOX haploinsufficiency. The conclusion is that GH therapy, at the same dosage used in patients with TS, induces a sustained catch-up growth and a height velocity and adult height gain in short patients with SHOX haploinsufficiency.


2010 - Il controllo dell’appetito [Articolo su rivista]
Iughetti, Lorenzo; M., China; R., Berri; Predieri, Barbara; F., Balli
abstract

Appetite control is executed through the fi ne regulationbetween calories and energy expenditure, in the dailyexperience of hunger and fulfi llness. Nowadays thedisregulation of this system is frequent, due to the increasedfood availability and through the interaction with environmental factors that determine hyperfagia and can cause obesity.This regulation system is constituted of peripheral nervous system, gastrointestinal system, endocrine system and of adipose tissue that integrate in central nervous system and in particular in hypothalamus, creating an homeostatic system.The comprehension of physiological processes that modulate body weight is necessary to establish therapies for this problem wherediet is often ineffective


2010 - Insulin resistance is a risk factor for high blood pressure regardless of body size and fat distribution in obese children. [Articolo su rivista]
Maffeis, C; Banzato, C; Brambilla, P; Cerutti, F; Corciulo, N; Cuccarolo, G; Di Pietro, M; Franzese, A; Gennari, M; Balsamo, A; Grugni, G; Iughetti, Lorenzo; Del Giudice, Em; Petri, A; Trada, M; Yiannakou, P.
abstract

BACKGROUND AND AIM: The prevalence of children with hypertension is increasing, especially in obese children. This study was to assess the relationship between blood pressure, indexes of adiposity, body fat distribution and insulin resistance. METHODS AND RESULTS:Sample: 1044 children (M/F: 484/560; aged 6-11 years). Anthropometry and blood pressure were measured and fasting blood samples were tested for triacylglycerol, total cholesterol, HDL cholesterol, glucose, insulin and ALT. The prevalence of high blood pressure in overweight males and females was 14.3 and 6.4%, respectively (chi(2)=16.73, p<0.001) and in obese it was 40.4 and 32.8%, respectively (chi(2)=5.56, p<0.001). High blood pressure increased progressively with BMI z-score categories (chi(2)=67.99, p<0.001) as well as with waist/height ratio (W/Hr) categories (chi(2)=23.51, p<0.001). Hypertensive subject had significantly higher insulin (15.6+/-9.8 vs 11.9+/-7.2, p<0.001 and 20.63+/-14.7 vs 15.26+/-9.8, p<0.001 in males and females respectively) and HOMA(IR) (3.23+/-2.1 vs 2.42+/-1.49, p<0.001 and 4.12+/-2.87 vs 3.07+/-1.98, p<0.001 in males and in females, respectively) than non-hypertensive ones. Among metabolic and cardiovascular risk factors, HOMA(IR) was the only variable able to predict high blood pressure in obese boys and girls, in addition to BMI or body fat distribution (waist, W/Hr). The highest HOMA(IR) category was the most important predicting factor of high blood pressure in overweight and obese children in addition to body size or body fat distribution.CONCLUSIONS: Blood pressure is associated with the degree of overweight and the indices of body fat distribution. Insulin resistance is an independent additional risk factor for hypertension.


2010 - Longitudinal study of the endothelial function in children and adolescents affected by type 1 diabetes mellitus [Abstract in Rivista]
Iughetti, Lorenzo; Rossi, Rosario; Predieri, Barbara; Nuzzo, A; Bruzzi, Patrizia; Salvini, Anna; Patianna, Viviana; Delle Donne, Grazia; Modena, Maria Grazia
abstract

Introduction: Cardiovascular diseases are the main cause of mortality and morbidity in patients affected by Type 1 Diabetes. The endothelial dysfunction, a precocious stage of the atherosclerotic process, can be analyzed through the brachial flow-mediated dilatation and through the evaluation, of the arterial stiffness. Objective: The aim of this study is to evaluate the presence of subclinical cardiovascular alterations and their development in pediatric patients with T1DM. Methods: A total of 42 patients with T1DM (18 females, 11.5 ± 3.6 years) entered this study. In all patients we analyzed the auxological, laboratory and clinical data (CT, HDL, LDL, TG, Glycemia, HbA1c, blood pressure (SBP-DBP). The evaluation of the endothelial function was obtained through the flow mediated dilation method (FMD), while stiffness was measured using pulse wave analysis (PWA). The measurements were repeated after 2 years and were compared with 30 healthy children and adolescents. Results: At baseline FMD values were significantly reduced in children with T1DM (4.32 ± 8.36%; vs. 9.78 ± 6.1, P = 0.003) and the lipid values result normal with a significant improvement during the study (P < 0.05). After 2 years while FMD significantly impaired, HbA1c and lipid values remained unchanged. The regression model allowed to identify CT (b = 0.683, P = 0.025) and LDL (b = )0.676, P = 0.025) as FMD predictive factors. The PWA analysis showed in females a slight decrease in myocardial perfusion. Conclusions: This study confirms that in children with T1DM the endothelial function can be already altered. The Pulse Wave Analysis results helpful to precociously individuate pathological alterations of the arterial elasticity and stratification of the cardiovascular risk.


2010 - "Mi voglio bene": a pediatrician-based randomized controlled trial for the prevention of obesity in Italian preschool children. [Articolo su rivista]
Brambilla, P; Bedogni, G; Buongiovanni, C; Brusoni, G; Di Mauro, G; Di Pietro, M; Giussani, M; Gnecchi, M; Iughetti, Lorenzo; Manzoni, P; Sticco, M; Bernasconi, S.
abstract

BACKGROUND: The first years of life are crucial to start preventive interventions that can have an impact on lifestyle and later overweight and obesity. Under the Italian National Health System (INHS), children are cared for by family pediatricians who perform health balances at regular intervals. The Italian Society of Preventive and Social Pediatrics (SIPPS) has designed a randomized controlled trial (RCT) to evaluate the effectiveness of family pediatricians for the prevention of childhood obesity in preschool children. We report the rationale and protocol of such trial, named the "Mi voglio bene" ("I love myself") study. METHODS: "Mi voglio bene" is a parallel-arm RCT. Family pediatricians willing to participate to the trial will be randomly assigned to a control group and to an experimental group. The control group will provide the usual standard of care while the experimental group will implement 10 preventive actions (promotion of breastfeeding, avoidance of solid foods, control of protein intake, avoidance of sugar-sweetened beverages, avoidance of bottle, active means of transportation, identification of early adiposity rebound, limitation of television viewing, promotion of movement, and teaching portion size) at 10 time points during a 6-yr follow-up. The main outcome measures is the prevalence of overweight and obesity at 6 years of age. The experimental intervention is expected to reduce the prevalence of overweight and obesity from 25% to 20% and the study requires a total of 3610 children. Each pediatrician will enroll 30 consecutive newborns into the study so that a total of 120 pediatricians will participate to the study. DISCUSSION: "Mi voglio bene" is expected to provide important information for the INHS and possibly other institutional child care settings about the effectiveness of a pediatrician-based approach to the prevention of childhood obesity. We published this study protocol with the aim of opening a discussion with all people interested in fighting childhood obesity and to receive useful criticisms.


2010 - Multicenter study on rhGH treatment in patients with SHOX-Deficiency. [Abstract in Rivista]
Iughetti, Lorenzo; S., Vannelli; P., Pirazzoli; S., Bertelloni; G., Radetti; M. E., Street; S., Madeo; L., Mazzanti; S., Ghione; B., Stasiowska; Predieri, Barbara
abstract

Background: Mutations of the Short Stature Homeobox-containing (SHOX) gene on the pseudoautosomal region of the sex chromosomes(Xp22 and Yp11.3) are correlated with short stature. Patients with SHOX-Deficiency (SHOX-D) have different degrees of growthimpairment and generally remain short in adulthood. Turner Syndrome (TS) subjects present a SHOX haploinsufficiency that appears to be substantially responsible for their short stature. Considering the positive effects obtained with GH therapy in patients with TS, this treatment was also proposed in short stature due to isolated SHOX-D.Objective: The aim of our retrospective study was to analyze height gain and safety of rhGH therapy in patients with SHOX-D.Methods:We studied twelve patients (7 females, 5 males; age 8.7 ± 2.9 years; range 4.9-13.16 years)) with isolated SHOX-D geneticallyconfirmed, all with height SDS < 1.5, target height SDS -1.29 ± 0.65, and in 1 patient with SHOX-D combined with trichorhinophalangealsyndrome. All patients were treated for at least 1 year (2.49 ± 1.45; range 1-6.43) with rhGH (mean dosage of 0.026 ± 0.003mg/kg/day). Results:: GH treatment significantly improved Growth Velocity SDS (2.11 ± 1.42) and height SDS (from -2.03 ± 0.22 to -1.62 ± 0.45, p<0.03), without affecting BMI SDS (from 0.18 ± 1.06 to 0.45 ± 1.74). In the patient with SHOX-D and trichorhinophalangeal syndrome GH failed to improve height SDS. Madelung deformity, if present at the start of therapy, did not deteriorate during follow-up. The better catch-up growth was obtained in the 3 younger patients. There were no discontinuation due to adverse events and no serious adverse events were reported for subjects with SHOX-D.Conclusions: The growth velocity in subjects with SHOX-D was significantly accelerated during rhGH therapy and resulted in a significant gain of height. Our data confirm the few reported evidences showing that GH therapy has a positive statural effect in SHOX haploinsufficiency without cause serious adverse events. Further longitudinal studies are needed to confirm these preliminary results.


2010 - Plasma Brain-Derived Neurotrophic Factor (BDNF) Concentrations in Children and Adolescents [Abstract in Rivista]
Predieri, Barbara; Iughetti, Lorenzo; E., Casarosa; Patianna, VIVIANA DORA; A., Bonetti; S., Madeo; S., Luisi
abstract

Background:BDNF is a mediator of neuronal plasticity and influences learning, memory, cognitive behaviour and reproductive system.Objective:Aim of this study is to assess BDNF concentrations in healthy children and adolescents according to pubertal status.Methods:One hundred ten health children, adolescents and young adults were recruited. BDNF concentrations were measured by ELISA.Platelet count (PTL), estradiol (E2), testosterone (T), and IGF-1 were also assessed. Non parametric statistical analysis was performed.The association between potential predictors and BDNF values was evaluated throught multivariate logistic regression model [sex, age,height SDS, z-BMI, pubertal status (no/yes), PTL, E2, T]Results:The characteristics of the patients are reported in the Table. Girls displayed higher BDNF levels than boys. BDNF concentrationswere not significantly different between prepubertal and pubertal subjects while its levels resulted lower in pubertal boys than pubertalones and both prepubertal and pubertal girls (x2=9.74; Kruskal-Wallis test= 8.52; p = 0.036). We have found a significant correlationbetween the values of BDNF and PTL (r=0.333; p=0.007), chronological age (r=-0.225; p=0.019), height (r=-0.231; p=0.016), and T (r=-0.261; p=0.006) . In prepubertal group BDNF values were correlated only with PTL (r=0.325; p=0.025), while in pubertal subjects they were correlated with z-BMI (r=0.293; p=0.038). The main predictor of BDNF was PTL (r=0.357, p=0.008).Conclusions:Our data suggests that serum BDNF is positively correlated with both platelet count and z-BMI and negatively associated with age. Thus, serum BDNF concentrations in children may need to be interpreted with age-specific and platelet count-specific standards. BDNF level was partially explained by PTL (R2=22%), but other parameters are probably involved in its determination (BMI, puberty). Furher studies are necessary to better understand the role of this neurotrophin, expressed in the central and peripheral nervous system, in pediatric subjects.


2010 - Prader Willi syndrome and growth hormone treatment in children and adults. [Articolo su rivista]
Iughetti, Lorenzo; China, M; Patianna, V; Predieri, Barbara
abstract

Prader Willi syndrome (PWS) is a complex multi system genetic disorder, including severe neonatal hypotonia, early onset of hyperphagia and development of morbid obesity, short stature, hypogonadism, learning disabilities, behavioural problems and psychiatric phenotypes.PWS patients’ body composition resembles that of individuals with growth hormone deficiency, including short stature and reduced lean body mass with concomitant increased fat mass. Previous studies suggest that GH therapy may be beneficial in children and adults with PWS. While short term benefits of treatment with GH have been shown, whether these beneficial effects are dose dependent and persist or wane with prolonged therapy remains uncertain in adults. This review focuses on the benefits, safety and adverse effects of the GH treatment in children and adults.


2010 - PROGETTO DI PREVENZIONE DELL’OBESITà INFANTILE TRA 0 E 6 ANNI “MI VOGLIO BENE”. [Articolo su rivista]
P., Brambilla; G., Bedogni; C., Bongiovanni; G., Brusoni; G., Di Mauro; M., Di Pietro; M., Giussani; M., Gnecchi; Iughetti, Lorenzo; M., Sticco; S., Bernasconi
abstract

Background. The high prevalence of obesity at age 6 suggests the adoption of prevention programmes starting from birth. The main characteristics of a prevention pilot study to be undertaken by Family Paediatricians (FP) are described. Aim. We identified 10 actions, each of them based on published studies. The aim of the project is to verify the effectiveness of their adoption on obesity prevalence at 6 years of age, by means of a randomized controlled intervention study. Methods. 120 FP will follow up a total of 3,600 newborns up to age 6 by means of 10 scheduled health checks. FP will illustrate 10 simple preventive actions in a structured project, 6 of them concerning nutrition (breast feeding up to 6 months, complementary food starting no early than 6 months, controlled protein intake during first 2 years, no caloric drinks, stop bottle use within age 2, and use of colour food photography atlas for correct portion size for pre-school age), 3 of them concerning lifestyle (discourage of inactive transportation, promotion of early physical activity by means of leisure tools, control of sedentary behaviours), and 1 of them about the identification of an early adiposity rebound. The main outcome measure is Body Mass Index at age 6. Control group children will be checked only for auxological parameters. Discussion. The results of this project could offer useful data for the adoption of effective early obesity prevention strategies.


2010 - Protocollo per la valutazione di disfagia nel bambino con patologia neurologica grave presso l’UO di Pediatria dell’Azienda Ospedaliero-Universitaria Policlinico di Modena [Abstract in Rivista]
Frassoldati, Rossella; D., Soloperto; M. P., Luppi; G., Bergamini; C., Rossi; G., Vivi; C., Molinari; S., Cipolli; S., Leoni; A., Guerra; Genovese, Elisabetta; Presutti, Livio; Iughetti, Lorenzo; Paolucci, Paolo
abstract

Secondo uno studio di Reilly (1996) il riscontro di disfunzioni motorie orali nei soggetti con PCI arriva fino al 90%, e la prevalenza di compromissione della fase orale e faringea è del 38%


2010 - Quando il vomito persiste [Abstract in Rivista]
Bonvicini, Chiara; Tosetti, Giulia; G., Di Fazzio; Balestri, Eleonora; Baroni, Lorenza; Tediosi, Giulia; A. R., Di Biase; A., Bianchini; P., Repetto; Iughetti, Lorenzo
abstract

Le stenosi duodenali in età pediatrica sono più frequentemente di origine congenita, possono essere complete (atresia) o incomplete. Nelle incomplete si ha un restringimento del lume duodenale di natura intrinseca o estrinseca. Le cause più frequenti sono il diaframma duodenale, il difetto di rotazione, le briglie di Ladd e il pancreas anulare. Il pancreas anulare è caratterizzato da una banda di tessuto pancreatico che circonda la seconda parte del duodeno in continuità con la testa del pancreas restringendo il lume intestinale a tale livello. La sintomatologia principale è rappresentata dal vomito che si manifesta precocemente nelle stenosi complete; nelle forme incomplete la sintomatologia può essere più sfumata e tardiva quindi la diagnosi può rimanere misconosciuta a lungo. Di fronte alla presenza di vomito persistente è quindi importante, una volta escluse le cause più frequenti per età, proseguire con le indagini al fine di escludere quadri malformativi


2010 - Se non è Guillain-Barré... ?!? [Abstract in Rivista]
Fornaciari, Sara; Codifava, Margherita; Lami, Francesca; Bigi, Elena; A., Guerra; Iughetti, Lorenzo
abstract

La MAT è una sindrome clinica neurologica provocata da infiammazione del midollo spinale, monofasica e monofocale, che si presenta isolatamente o nell’ambito di un’altra malattia (infettiva, autoimmune, infiammatoria, demielinizzante, neoplastica, paraneoplastica, vascolare). L’esordio è improvviso, con deficit neurologico (a rapida evoluzione, dipendente dal livello midollare interessato), dolore addominale o lombare, debolezza e parestesie degli arti inferiori, compromissione della sensibilità termo-dolorifica al di sotto del livello interessato e disfunzioni autonomiche. Il trattamento specifico è rappresentato da alte dosi di cortisosteroidi, associate a terapia di supporto di eventuali disturbi autonomici e a fisioterapia, da intraprendere precocemente. L’esame neuroradiologico consente la diagnosi di MAT tra le patologie a presentazione simile (Sdr. di Guillain-Barré, neoplasie del midollo spinale e dell’osso, Sdr. della cauda equina e cono midollare, disturbo demielinizzante, malformazioni vascolari), fornendo gli strumenti per l’opportuno intervento terapeutico.


2010 - SHOX region mutation in Leri-Weill dischondrosteosis (LWS) [Abstract in Rivista]
Iughetti, Lorenzo; L., Capone; T., Arrigo; S., Bernasconi; F., Buzi; L., Cavallo; F., Chiarelli; M., Cisternino; C., Danesino; L., Garavelli; R., Lorini; A., Liotta; A., Marsciani; A., Pasquino; A., Percesepe; P., Porcelli; G., Radetti; M., Seri; A., Salvatoni; R., Tenconi; G., Weber; Predieri, Barbara; A., Forabosco
abstract

Background:LWS, a dominantly inherited skeletal dysplasia with short stature, mesomelia, and Madelung deformity, is the consequenceof haploinsufficiency of the SHOX gene caused by deletions or point mutations. Heterozygous deletions downstream this gene, involvingthe gene enhancers, have been recently demonstrated to cause LWS.Objective and hypotheses:We report the results obtained in 59 patients presenting with LWS clinical findings, analyzed both for SHOXgene and its enhancers.Methods:All samples were examined for copy number alterations within the SHOX gene and the PAR1 region by MLPA and/or bymicrosatellite analysis. All patients negative for deletion were screened for point mutations by direct sequencing of all the coding exons and the intron/exon boundaries of the gene isoform A (exon 2-6a).Results:Point mutations were detected in 5/59 families (8,4%; 2 in exon 3, 2 in exon 4 and 1 in exon 6a). The majority of mutations aremissense mutations (4 missense and 1 frameshift mutations) occurring predominantly in the homeodomain region respect to the OAR domain. In 23/59 (39%) families large deletions were found. Two (5%) involved only the SHOX enhancers region and were detected in 2 girl previously negative for SHOX mutations; one (3,9%) is an intragenic deletion involving only the 3 terminal exons, undiagnosed before use of MLPA; the remaining deletions (51%) involved the entire gene. Mutations were globally found in 47% of the families, below what was expected (reported mutation rate 55-64%). Deletions occur more frequently than point mutations (39 % vs 8,4%).Conclusions:The examination of patients previously resulted negative for SHOX alterations permitted to find the enhancers regiondeletion in 2 unrelated patients. These data underlies the necessity of re-analyze for enhancer deletions all “old” samples with an intactcoding region. Despite the characterization of this new class of mutations involving the enhancers region, the mutation rate in LWDpatients is far from 100%, suggesting the idea that other regulative elements may be involved.


2010 - Solo febbre e tosse? [Abstract in Rivista]
Balestri, Eleonora; Baroni, Lorenza; Tediosi, Giulia; Bonvicini, Chiara; G., Di Fazzio; Tosetti, Giulia; A., Guerra; Iughetti, Lorenzo
abstract

Anche situazioni molto comuni e banali, come un’infezione delle vie aeree associata a tosse insistente, in assenza di fattori predisponenti evidenti tranne, come nel nostro caso, una lassità ligamentosa degli arti inferiori, possono accompagnarsi a PMS e necessitare di attento follow-up per il rischio di sviluppo di complicanze, come pneumomediastino tensivo, pneumotorace e pneumopericardio, che, sebbene rare, possono richiedere procedure invasive d’urgenza. Raccomandazioni follow-up: limitazioni immediate, no voli aerei per 6 mesi o sport o attività fisiche violente; limitazioni potenzialmente a vita, attività con variazioni pressorie repentine, subacquea, paracadutismo ecc.


2010 - Stroke in paziente con drepanocitosi con precedente riscontro di infarti silenti e deficit cognitivi [Abstract in Rivista]
Tediosi, Giulia; Guerzoni, Maria Elena; Baroni, Lorenza; Balestri, Eleonora; Di Fazzio, G; Bonvicini, Chiara; Bigi, Elena; Migliozzi, C; Pugliese, M; Palazzi, G; Cano, C; Cellini, M; Cavalleri, F; Paolucci, Paolo; Guerra, ; Iughetti, Lorenzo
abstract

Le complicanze neurologiche della drepanocitosi sono relativamente rare in età pediatrica. Tra queste l’infarto silente è definito come una sofferenza vascolare del parenchima cerebrale con formazione di un’area malacica di dimensioni inferiori a 1,5 cm, senza deficit neurologici focali. A distanza si possono presentare deficit neurocognitivi, di apprendimento e scarso rendimento scolastico, con un aumento del rischio per stroke manifesti.


2010 - The SHOX region and its mutations [Articolo su rivista]
Capone, L.; Iughetti, L.; Sabatini, S.; Bacciaglia, A.; Forabosco, A.
abstract

The short stature homeobox-containing (SHOX) gene lies in the pseudoautosomal region 1 (PAR1) that comprises 2.6 Mb of the short-arm tips of both the X and Y chromosomes. It is known that its heterozygous mutations cause Leri-Weill dyschondrosteosis (LWD) (OMIM #127300), while its homozygous mutations cause a severe form of dwarfism known as Langer mesomelic dysplasia (LMD) (OMIM #249700). The analysis of 238 LWD patients between 1998 and 2007 by multiple authors shows a prevalence of deletions (46.4%) compared to point mutations (21.2%). On the whole, deletions and point mutations account for about 67% of LWD patients. SHOX is located within a 1000 kb desert region without genes. The comparative genomic analysis of this region between genomes of different vertebrates has led to the identification of evolutionarily conserved non-coding DNA elements (CNE). Further functional studies have shown that one of these CNE downstream of the SHOX gene is necessary for the expression of SHOX; this is considered to be typical "enhancer" activity. Including the enhancer, the overall mutation of the SHOX region in LWD patients does not hold in 100% of cases. Various authors have demonstrated the existence of other CNE both downstream and upstream of SHOX regions. The resulting conclusion is that it is necessary to reanalyze all LWD/LMD patients without SHOX mutations for the presence of mutations in the 5'- and 3'-flanking SHOX regions.


2010 - Toxic environment and obesity pandemia: is there a relationship? [Articolo su rivista]
Latini, G; Gallo, F; Iughetti, Lorenzo
abstract

Obesity is a multi-factorial disease, resulting from genes, environment and behaviour interactions, representing the most common metabolic disorder in the Western Hemisphere. Its prevalence has dramatically risen during the last three decades, reaching worldwide epidemic proportions. Recent cumulating evidence suggests that obesity may represent an adverse health consequence of exposure during the main developmental stage to environmental chemicals disrupting endocrine function. Moreover these chemicals can be involved in the development of obesity-related metabolic and cardiovascular diseases. Further research is needed to elucidate the involved mechanisms, the relationship between this exposure and the obesity pandemia as well as hazard identification.


2010 - Type 1 diabetes (T1DM) in children and adolescents of immigrated families in Emilia-Romagna (Italy). [Articolo su rivista]
Banin, P; Rimondi, F; De Togni, A; Cantoni, S; Chiari, G; Iughetti, Lorenzo; Salardi, S; Zucchini, S; Marsciani, A; Suprani, T; Tarchini, L; Tozzola, A; Xella, R; Marsella, M; De Sanctis, V.
abstract

Background and aim of the work: The etiology and natural history of T1DM are still unknown but certainly both genetics and environmental factors contribute to the development of the disease. Migrationstudies are an important tool to better understand the role of the environment. The aim of this study was to investigate some variables in diabetic children of immigrant families living in Emilia-Romagna compared with Italian diabetic children living in the same region. Methods:We recruited 73 diabetic children from immigrant families and 707 Italian diabetic children. All children were cared by Pediatric Diabetes Units of Emilia-Romagna (10 centers). The investigated variables were: gender, current age, place of birth, parents’country of origin, age at diagnosis, HbA1c and insulin regimen. Results: No significant difference with reference to gender neither among the two ethnic groups, nor in the current mean age was observed. Mean age at diagnosis in the Italian children was lower than in immigrant patients born outside Italy -group A- (7.4 vs. 9.6, p<0.000) and higher compared to those born in Italy - group B- (7.4 vs. 5.7 p<0.003; A vs. B p<0.000). The immigrant patients showed higher mean HbA1c than Italian patients (8.8 vs. 8.2, p<0.009).Conclusions: A younger age at diagnosis of T1DM in immigrant children, born in Italy compared with those born in the country of origin, and with Italian patients, suggests the existence of some environmental determinants acquired with a more westernised lifestyle. Immigrant children have significantly poorer metaboliccontrol compared with western patients.


2010 - Una strana addominalgia [Abstract in Rivista]
Baroni, Lorenza; Tediosi, Giulia; P., Bruzzi; Bonvicini, Chiara; Balestri, Eleonora; G., Di Fazzio; A., Guerra; Iughetti, Lorenzo
abstract

L’angioedema ereditario è una rara patologia autosomica dominante causata da deficit congenito dell’inibitore di C1 esterasi. Questo deficit porta ad aumento del rilascio locale di mediatori vasoattivi, soprattutto la bradichinina, con maggior permeabilità dei piccoli vasi, accumulo di liquido extravascolare e quindi edema. Caratteristica dell’angioedema è il ripetersi di episodi che interessano il sottocute (estremità, volto, tronco e genitali) o la sottomucosa (intestino e laringe). L’episodio acuto può essere scatenato da un trauma, uno stato d’ansia, o insorgere spontaneamente. Quando è colpito il tratto gastrointestinale i pazienti presentano nausea, vomito e dolore addominale.


2010 - Unexpected phenotype in a boy with trisomy of the SHOX gene. [Articolo su rivista]
Iughetti, Lorenzo; Capone, L; Elsedfy, H; Bertorelli, R; Predieri, Barbara; Bruzzi, P; Forabosco, Antonino; El Kholy, M.
abstract

The assessment that heterozygous SHOX mutations leading to SHOX haploinsufficiency play a role in patients with idiopathic short stature (ISS) is already documented in the literature as well as the suggestion that additional copies of SHOX are strongly implicated in a condition of tall stature. However, we report the first case of short stature in a male associated with the presence of three copies of the SHOX gene. Through chromosomal analysis, using Multiplex Ligation-dependent Probe Amplification method of SHOX salsa P018B kit and microsatellite analysis, we identify a new interstitial isolated duplication of the SHOX gene and its enhancer caused by a larger duplication of the PAR1 region in a boy with ISS. Consequently, we propose the hypothesis that this chromosome re-arrangement disrupts the regular interaction between the enhancer and promoter, resulting in a transcription block, thus producing a lack of gene activation, causing the clinical feature of short stature.


2010 - Uno strano “ballo” [Abstract in Rivista]
G., Di Fazzio; Tosetti, Giulia; Bonvicini, Chiara; Balestri, Eleonora; Baroni, Lorenza; Tediosi, Giulia; S., Gavioli; A., Guerra; Iughetti, Lorenzo
abstract

La malattia reumatica (MR) è in fase di recrudescenza a partire dagli anni ottanta. Insorge dopo 2 settimane da un episodio di faringite streptococcica, per danno anticorpale da anticorpi diretti contro la proteina M del SBA che cross reagiscono con proteine delle articolazioni, endocardio, e SNC. La diagnosi della MR si basa tutt’oggi sui criteri di Jones (revisionati nel 1992), mentre l’ecocardiografia costituisce il principale strumento per monitorare le lesioni valvolari mitraliche e aortiche che costituiscono la più grave complicanza della MR, pur essendo ancora controverso il ruolo dell’ecocardiografia nella diagnosi di lesioni non clinicamente evidenti. La terapia si basa sulla profilassi primaria con trattamento della faringite e sulla profilassi secondaria con benzatin-penicillina, la cui durata è variabile a seconda dell’entità dell’interessamento cardiaco da 5 anni a tutta la vita.


2009 - A consensus document on the role of breakfast in the attainment and maintenance of health and wellness. [Articolo su rivista]
Marangoni, F; Poli, A; Agostoni, C; Di Pietro, P; Cricelli, C; Brignoli, O; Fatati, G; Giovannini, M; Riva, E; Marelli, G; Porrini, M; Rotella, Cm; Mele, G; Iughetti, Lorenzo; Paoletti, R.
abstract

Considerable evidences, mainly derived from epidemiological studies, but also supported by few intervention trials, confirm the role of breakfast as part of a healthful and balanced diet, and suggest that its benefits may be partly immediate and partly mediated by the macro and micro nutrients supplied with this meal. The regular consumption of breakfast providing about 15-20% of the daily caloric intake is associated with a higher likelihood to reach the recommendeddietary levels of some micronutrients and with a reduced risk of developing obesity, cardiovascular events, and diabetes, possibly by controlling some of their risk factors. Children and adolescents who regularly have breakfast also exhibit short-term improvement in school performance. Grain-derived products such as bread, biscuits,toast bread and ready-to-eat breakfast cereals should provide the major proportion of carbohydrates. Milk and milk-derived products - within a balanced breakfast - represent the main sources of proteins, lipids, and some micronutrients.An appropriate turnover of different breakfast models might favor the regular consumption of complete breakfasts, extending its favorable effects to both the psyco-physic efficiency and the feeling of satiety inthe next hours, concomitantly contributing to a general protective effect on health.


2009 - A survey on Prader-Willi syndrome in the Italian population: prevalence of historical and clinical signs. [Articolo su rivista]
Crinò, A; Di Giorgio, G; Livieri, C; Grugni, G; Beccaria, L; Bosio, L; Corrias, A; Chiumello, G; Trifirò, G; Salvatoni, A; Tonini, G; Gargantini, L; de Toni, T; Valerio, G; Ragusa, L; Franzese, A; Rinaldi, Mm; Spera, S; Gattinara, Gc; Villani, S; Iughetti, Lorenzo
abstract

Prader-Willi syndrome (PWS) is characterized by hypotonia and feeding problems in neonatal period, hyperphagia and rapid weight gain after the first year of life, mental retardation, behavioral problems and hypogenitalism. For diagnosis, anamnestic and clinical criteria have been established by consensus in 1993 (Holm and Cassidy). Then, definitive genetic analysis became available. Subsequently revised criteria according to age have been proposed in 2001 in order to raise diagnostic suspicion to prompt genetic tests, avoiding expense of testing unnecessarily.The aim of our study was to analyse the frequency of anamnestic and clinical features in Italian PWS population in order to assess their validity in raising diagnostic suspicion and in identifying the patients to test genetically. We evaluated 147 patients with PWS (67 m, 80 f), aged 0.9-34.6 yrs (13.6 ± 6 yrs) with genetically confirmed diagnosis of PWS using the consensus diagnostic criteria. Data where classified according to age, sex and genotype. All PWS patients achieved the score according to the clinical diagnostic criteria.The frequency of features changed with age and sex. Sensitivities of some major clinical signs as neonatal hypotonia and learning problems (in patients > 6 yrs old) ranged from 96 to 100% in both sex. Cryptorchidism was present in 100% of cases, while female genital hypoplasia ranged from 50 to 75% without any significant difference between ages. Feeding problems in infancy varied from 25 to 82% in females and from 80 to 88% in males, meanwhile characteristic facial features varied from 67 to 100% in females and from 50 to 100% in males without any significant difference between ages. The sensitivity of hyperphagia and excessive weight gain increased with age, in both sex, reaching 100% after 13 years. The sensitivity of some minor and supportive criteria like characteristic behaviour problems, myopia, saliva alteration, skin picking, scoliosis and/or kyphosis, early adrenarche changed significantly with age. Speech defects and osteoporosis changed with age only in females. It is noticeable that some clinical signs as acromicria and behavioural problems, scoliosis and/or kyphosis, considered as minor or supportive by Holm and Cassidy, emerged to have higher sensitivity than some major criteria, and, therefore, more useful to support the diagnosis of the syndrome. Hypopigmentation and acromicria were significantly more frequent in subjects with deletion than those with UPD, meanwhile osteoporosis was more frequent in patients with UPD. This study demonstrates that some clinical characteristics are particularly frequent during specific ages of life and therefore confirms the necessity of a classification of criteria according to age as already suggested previously.


2009 - Antioxidant factors and endothelial function in children and adolescents with Type 1 diabetes mellitus [Abstract in Rivista]
Iughetti, Lorenzo; A., Lasagni; Rossi, Rosario; P., Appio; G., Delle Donne; A., Nuzzo; Patianna, VIVIANA DORA; Salvini, Annamaria; Modena, Maria Grazia; B., Bergamini; Predieri, Barbara
abstract

Our data demonstrated that in our T1DM patients A) the satisfactory glycemic control was coupled with normal lipid profile but increased oxidative parameters, B) the endothelial function was impaired (especially in boys), and C) there was no correlation between FMD and antioxidant status and glycemia. However, the relationship of FMD with LDL-C underline the possible role of a global metabolic control.


2009 - Current and future drugs for appetite regulation and obesity treatment [Articolo su rivista]
Iughetti, L.; Berri, R.; China, M.; Predieri, B.
abstract

The growing worldwide prevalence of obesity needs urgent attention because the potential morbidity, mortality, and economic tolls have to be avoided. Despite obesity is known as a healthcare issue on an epidemic scale, it remains largely an unsolved medical problem. The successful management of obesity is theoretically possible through lifestyle changes, with diet modifications and increasing physical activity. However, low results by traditional treatments have inevitably prompted interest in the development of effective therapies, including pharmacological interventions and gastrointestinal surgery. As our knowledge of the physiological systems regulating food intake and body weight has considerably increased over the past decade, many studies have underlined the scientific and clinical relevance of potential treatments based on peripheral hormones or central neuropeptides signals. Here we have summarized the complex pattern of the appetite regulation, divided into central and peripheral mechanisms. In the second part of this paper, we have reviewed the currently approved and putative obesity therapies. Up to now only two drugs, sibutramine and orlistat have been approved by the Food and Drug Administration for long term use, but several other medications are currently used to cure severe obesity and many other are developing. Thus, in the last part, we have analyzed recent literature and patents describing new and upcoming molecules. The new anti-obesity drugs under clinical development include agents affecting peripheral and central mechanisms. Further investigations are needed to approve these upcoming therapeutic agents for the treatment of obesity.


2009 - Drugs for children with hypercholesterolemia: be cautious. [Articolo su rivista]
Iughetti, Lorenzo
abstract

While the efficacy in childhood of other antilipidic drugs (Bile acid-binding resins, Statins) are proved with long-term studies, the long-term efficacy of Ezetimibe in pediatric age remains to be ascertained, also using surrogate markers for atherosclerosis, as intimal-media thickness and endothelial function. More important, the recent concern about the augmented cancer risk related to the use of Ezetimibe in adults strongly raises the question about the ethics of the use of this drug in children. In any way, to avoid a misuse of Ezetimibe and to confirm the findings of the anecdotic studies published until now, it’s time to perform a randomized, multicentre. double-blinded, placebo-controlled study. Meanwhile. despite the recent liberalization by AAP, we maintain a cautious approach in the use of any antilipidic drugs in children, tailoring the treatment on the basis of individual risk.


2009 - Endothelial function in adolescents with type 1 diabetes mellitus (TIDM) [Funzione endoteliale in adolescenti con diabete di tipo 1], [Articolo su rivista]
Bruzzi, Patrizia; Vellani, Giulia; Predieri, Barbara; Delle Donne, G; Iaccarino, D; Madeo, Simona Filomena; Quitadamo, Al; Pellicanò, F; Rossi, Rosario; Modena, Maria Grazia; Balli, F; Iughetti, Lorenzo
abstract

Patients with type 1 diabetes mellitus (T1DM) have an increased risk of cardiovascular complications related to the duration of diabetes and the degree of glycemic control. Impared flow-mediated dilation (FMD) has been used to evaluate the vascular function. Aim is to evaluate longitudinally changes of FMD in T1DM adolescents. Methods. Twenty-five adolescents (14 males and 11 females, aged 12.9 ± 2.3 years) with T1DM (duration of disease 54.1 ± 41.1 months) entered the study. In all patients glycaemia, glycated haemoglobin (HbA1c), lipid values, and FMD were determined at the beginning and after 30.20 months. Vascular function was assessed by measurement of endothelium-dependent vasodilatation of the brachial artery using a high-sensibility ultrasound system. FMD was expressed as percentage change of diameter of the artery following reactive hyperemia from baseline. Results. At the end of the study, the mean value of FMD was significantly worsted (6.8 ± 11.8 vs 1.4 ± 7.8; p = 0.04). No correlation was demonstrated between FMD and lipid profile and HbA1c. Longitudinally boys had significantly lower FMD than girls (-2.3 ± 6.3 vs 6.4 ± 6.8; p = 0.002). Conclusion. Adolescents with T1DM have a worse FMD, more evident in males, and apparently unrelated to glycemic control.


2009 - Glycaemic Control in Kenyan Children and Adolescents with Type1 Diabetes Mellitus [Abstract in Rivista]
T., Ngwiri; F., Were; P., Ngugi; Iughetti, Lorenzo
abstract

The study demonstrate that the prevalence of poor control in type 1 diabetic children and adolescents in Kenyan children is far to be acceptable and the great majority of patients may be at high risk for the precocious development of microvascular complications. Adolescent patients have particularly poor control so comprise a special high risk group in the diabetes clinic. The data strongly support the necessity that children and adolescents with T1DM in Kenya receive more aggressive management and follow-up than is currently being provided.Probably the possiblity to obtain analog long acting insulin could be important to improve metabolic control.


2009 - High g-glutamyl-transferase fractions as new markers to identify non-alcoholic fatty liver disease in childhood obesity [Abstract in Rivista]
Predieri, Barbara; Bruzzi, Patrizia; Lami, Francesca; L., Miglioli; S., Bellentani; Vellani, Giulia; F., Balli; A., Gastaldelli; Iughetti, Lorenzo
abstract

The system of advanced glycation end products (AGEs)AGEs and their soluble receptor (sRAGE) could play a role in the development of non-alcoholic fatty liver disease (NAFLD). Recently gamma-glutamyl-transferase (GGT) at values within the normal range, has been associated with evolution of atherosclerotic processes and predicts the onset and outcome of related diseases.The aim of the present study was to determine distinct GGT fractions in obese subjects with and without NAFLD and with serum GGT activity within the high-normal range. Moreover, we try to indentify relationships between the presence of steatosis with ALT, GGT and GGT fractions, hyperlipidemia, and sRAGE.28 obese children and adolescents (20 boys and 8 girls aged 11.9±2.77 years; height SDS 0.55±1.52; BMI SDS 3.11±0.55) were included in the study and were divided in Group 1 (14 with NAFLD) and Group 2 (14 no-NAFLD). Total GGT values were determined by enzyme kinetic assay. Separation of GGT fractions on the basis of their molecular weight was performed through liquid chromatography. sRAGE levels were determined using an ELISA kit.Tryglicerides, GGT, big-GGT (b-GGT), free-GGT (f-GGT) values were significantly higher in Group 1 than in Group 2, while sRAGE levels were significantly lower in Group 1. No other significant difference was found between groups [table1]. A significant negative correlation was demonstrated between sRAGE and GGT (r=-0.49), b-GGT (r=-0.39), small-GGT (s-GGT) (r=-0.47), f-GGT (r=-0.44). GGT activity was positively associated with total cholesterol (r=0.41) and triglycerides (r=0.42); the same significant correlation was demonstrated between the s-GGT fraction and total cholesterol (r=0.44) and triglycerides (r=0.42). f-GGT was the predominant fraction in Group 2, whereas in Group 1 we found a relative increase in s-GGT and b-GGT fractions. In obese NAFLD patients sRAGE significantly and negatively correlates only with s-GGT (r=-0.62).Our data demonstate that definition of specific predictive GGT fraction profile could be used to identify obese children with NAFLD that had higher GGT and lower sRAGE levels than their lean obese counterpart. It is conceivable that s-GGT they may be considered as primary marker of liver injury and as a surrogate for suspected fatty liver. Moreover, the AGEs-RAGE system could play a role in the pathogenesis of NAFLD in childhood obesity.


2009 - Influence of the Exon 3 – deleted polymorphism of the GH receptor on glucose and lipid metabolism in GH treated subjects with Prader-Willi syndrome: results of a preliminary study [Abstract in Rivista]
C., Donati; M., Baiocchi; P., Mella; A., Pilotta; A., Crinò; Iughetti, Lorenzo; G., Grugni; A., Salvatoni; F., Buzi
abstract

GH has contra-insulin actions and exogenous GH can reversibly reduce insulin sensitivity in patients treated with GH. It has been recently reported that the exon 3 – deleted (d3) isoform of the GH receptor (GHR) appears to be preventive for type 2 diabetes mellitus in adult subjects (GH&IGF Res 2007;17:392). Aim of this study was to investigate possible influences of the GHR-d3 isoform on glucose metabolism, lipid profile and BMI in children with Prader-Willi syndrome (PWS) treated with GH . We studied 44 PWS subjects (19 male). Mean age was 25.3 (range: 3.0-42.8) years. Of the 44 subjects, 32 had been (n° 9) or were being (n° 23) treated with GH at a mean dose of 0.06 mg/kg/week, while the remaining 12 never received GH therapy, and were therefore used to analyse the sole baseline variables. Patients' genotype at GHR-exon 3 locus was determined by simple multiplex PCR. Height-SDS, BMI-SDS, fasting glucose, insulin, total and HDL-cholesterol, triglycerides, oral glucose tolerance test (OGTT), QUICKI and HOMA-R indexes were regularly evaluated during treatment. Informed written consent was obtained from the subjects and/or their parents where appropriate. The full-length (fl) GHR exon 3 isoform was found in 21 subjects in homozygosity (group fl); d3 was found in 21 subjects in heterozygosity and in 2 in homozygosity (group d3), which corresponds to the common distribution of the exon-3 isoforms in the general population. No differences in the above mentioned parameters were found comparing the two groups at treatment start, during and at the end of treatment. Furthermore, height-SDS and BMI-SDS did not differ between the two groups neither at baseline or during treatment. On the basis of these preliminary data, d3 does not seem to influence glucose and fat metabolism during GH treatment in PWS subjects.


2009 - Mandibuloacral dysplasia type A in childhood [Articolo su rivista]
Garavelli, L; D'Apice, Mr; Rivieri, F; Bertoli, M; Wischmeijer, A; Gelmini, C; De Nigris, V; Albertini, E; Rosato, S; Virdis, R; Bacchini, E; Dal Zotto, R; Banchini, G; Iughetti, Lorenzo; Bernasconi, S; Superti Furga, A; Novelli, G.
abstract

Mandibuloacral dysplasia type A (MADA) is characterized by growth retardation, postnatal onset of craniofacial anomalies with mandibular hypoplasia, progressive acral osteolysis, and skin changes including mottled pigmentation, skin atrophy, and lipodystrophy. Owing to its slowly progressive course, the syndrome has been recognized in adults, and pediatric case reports are scarce. We present the clinical case of two children in whom the diagnosis of MADA was made at an unusually early age. A 5-year-old boy presented with ocular proptosis, thin nose, and short and bulbous distal phalanges of fingers. A 4-year-old girl presented with round face and chubby cheeks, thin nose, bulbous fingertips, and type A lipodystrophy. In both, a skeletal survey showed wormian bones, thin clavicles, short distal phalanges of fingers and toes with acro-osteolysis. Both children were found to be homozygous for the recurrent missense mutation, c.1580G>A, (p.R527H) in exon 9 of the LMNA gene. Thus, the phenotype of MADA can be manifest in preschool age; diagnosis may be suggested by short and bulbous fingertips, facial features, and lipodystrophy, supported by the finding of acral osteolysis, and confirmed by mutation analysis.


2009 - Maturity-onset diabetes of the young in children with incidental hyperglycemia: A multicenter Italian study of 172 families [Articolo su rivista]
Lorini, R.; Klersy, C.; D'Annunzio, G.; Massa, O.; Minuto, N.; Iafusco, D.; Bellanne-Chantelot, C.; Frongia, A. P.; Toni, S.; Meschi, F.; Cerutti, F.; Barbetti, F.; Banin, P.; Cadario, F.; Calisti, L.; Cappa, M.; Crino, A.; Cherubini, V.; Chiari, G.; Vanelli, M.; Cotellessa, M.; D'Amato, E.; Cauvin, V.; Franzese, A.; Guazzarotti, L.; Iughetti, L.; Mancabitti, M. L.; Meossi, C.; Pinelli, L.; Pocecco, M.; Scaramuzza, A.; Sulli, N.; Visentin, A.
abstract

OBJECTIVE - To investigate the prevalence of maturity-onset diabetes of the young (MODY) in Italian children with incidental hyperglycemia. RESEARCH DESIGN AND METHODS - Among 748 subjects age 1-18 years with incidental hyperglycemia, minimal diagnostic criteria for MODY were met by 172 families. Mutational analyses of the glucokinase (GCK) and hepatocyte nuclear factor 1α (HNF1A) genes were performed. RESULTS - We identified 85 GCK gene mutations in 109 probands and 10 HNF1A mutations in 12 probands. In GCK patients, the median neonatal weight and age at the first evaluation were lower than those found in patients with HNF1A mutations. Median fasting plasma glucose and impaired fasting glucose/impaired glucose tolerance frequency after oral glucose tolerance testing were higher in GCK patients, who also showed a lower frequency of diabetes than HNF1A patients. CONCLUSIONS - GCK mutations are the prevailing cause of MODY (63.4%) when the index case is recruited in Italian children with incidental hyperglycemia. © 2009 by the American Diabetes Association.


2009 - Metabolic syndrome in children and adolescents with Prader-Willi syndrome: comparison between obese and non obese subjects. [Abstract in Rivista]
G., Grugni; A., Crinò; G., Bedogni; L., Bosio; M., Cappa; A., Corrias; M., Delvecchio; S., Di Candia; L., Gargantini; Iughetti, Lorenzo; L., Ragusa; M., Sacco; A., Salvatoni; A., Sartorio; G., Chiumello; P., Brambilla
abstract

The study compares the rprevalence of metabolic syndrome in children and adolescents with Prader-Willi syndrome with and without obesity.


2009 - New SHOX mutations in patients with idiopathic short stature [Abstract in Rivista]
Iughetti, Lorenzo; L., Capone; T., Arrigo; M., El Kholy; L., Cavallo; R., Bertorelli; S., Madeo; Predieri, Barbara; P., Appio; A., Forabosco
abstract

Mutations of SHOX (Short Stature Homeobox) gene are associated with the short stature in Turner syndrome, Leri-Weill dyschondrosteosis and in some patients (2 to 15%) with idiopathic short stature (ISS). Nevertheless, recently it has been characterized the SHOX gene enhancer, whose deletions has been shown to be responsible for the Leri-Weill syndrome.We report the results of a study carried out on patients with ISS, investigated for the presence of SHOX gene and SHOX enhancer mutations.Fifty-three patients of both sexes (2-18 years) entered this study. The inclusion criteria were: 1) height <3° centile; 2) normal stimulated GH values 3) absence of obvious skeletal anomalies 4) exclusion of chronic disorders causing short stature.All 53 samples were examined for the presence of deletions or duplications within the SHOX gene and the PAR1 region by Multiplex Ligation-dependent Probe Amplification (MLPA), using the SHOX salsa P018B kit (MRC-Holland); they were also examined for the presence of point mutations and small deletions and insertions by direct sequencing of all the coding exons and the intron/exon boundaries of the gene isoform A (from exon 2 to exon 6a) and of its enhancer.Sequencing analysis revealed no point mutations and small deletions or insertions that could account for the phenotype. On the contrary the molecular analysis of the entire PAR1 region by MLPA surprisingly revealed two large duplications. One patient presented a duplication of about 500Kb extending from exon 1 of the SHOX gene and encompassing its enhancer; another patient presented a smaller duplication involving only the enhancer. Both the duplications were further confirmed by using specific panels of microsatellites markers that resulted in triallelic patterns.For all we know, these mutations had never been described before and they could have a role in the short stature of these patients. In fact, in both cases, the duplication of PAR1 could disrupt the normal cis/regulation of transcription caused by the closeness of the duplicated regions. Such proximity could impede the regular interaction of each enhancer to each appropriate promoter, resulting in the alteration, most likely a reduction, of the normal transcriptional activity. This could be the reason why the duplication involving also a regulative element such as the enhancer is associated to a short stature phenotype while an extra copy of only the SHOX gene seems to determine tall stature.


2009 - Prevalence of pathogenetic MC4R mutations in Italian children with early onset obesity, tall stature and familial history of obesity. [Articolo su rivista]
Santoro, N; Cirillo, G; Xiang, Z; Tanas, R; Greggio, N; Morino, G; Iughetti, Lorenzo; Vottero, A; Salvatoni, A; DI PIETRO, M; Balsamo, A; Crino, A; Grandone, A; HASKELL LUEVANO, C; Perrone, L; MIRAGLIA DEL GIUDICE, E.
abstract

BackgroundMelanocortin-4-receptor (MC4R) mutations represent the most frequent genetic cause of non-syndromic early onset obesity. Children carrying MC4R mutations seem to show a particular phenotype characterized by early onset, severe obesity and high stature. To verify whether MC4R mutations are associated with this particular phenotype in the Italian pediatric population, we decided to screen the MC4R gene in a group of obese children selected on the basis of their phenotype.MethodsTo perform this study, a multicentric approach was designed. Particularly, to be enrolled in the study subjects needed to meet the following criteria: Body mass index ≥ 3 deviation scores according to age and sex, familiar history of obesity (at least one parent obese), obesity onset before the 10 years old, height ≥ 2 deviation scores. The coding region of MC4R gene was screened in 240 obese children (mean age 8.3 ± 3.1, mean BMI 30.8 ± 5.4) and in 200 controls (mean age 8.1 ± 2.8; mean BMI 14.2 ± 2.5).ResultsThree mutations have been found in five obese children. The S127L (C380T), found in three unrelated children, had been described and functionally characterized previously. The Q307X (C919T) and the Y332H (T994C) mutations were found in two patients. Functional studies showed that only Q307X impaired protein function.ConclusionThe low prevalence of MC4R mutations (1.6%) in this group of obese children selected according to the obesity degree, the tall stature and the family history of obesity was similar to the prevalence observed in previous screenings performed in obese adults and in not phenotypically selected obese children.


2009 - Severity of short stature and not GH peak at diagnosis is the major determinant of growth response to GH therapy in short subjects without severe GH deficiency [Abstract in Rivista]
S., Zucchini; M., Maghnie; M., Salerno; Iughetti, Lorenzo; M. E., Street; M., Caruso Nicoletti; M., Marsciani; M., Wasniewska; M., Delvecchio; V., Brunelli; A., Salvatoni
abstract

A diagnosis of GH deficiency (GHD) is still considered the gold standard for GH therapy in many European countries. Aim of the present multicentre study was to retrospectively analyze growth response to GH therapy and factors related to good response of 2 groups of short subjects with different GH secretion. Inclusion criteria for both groups, besides short stature, were absence of puberty, no other diseases affecting height (Ht) and treatment to adult Ht with same GH therapy schedule (7 mg/m2/wk or 0.20-25 mg/kg/wk). Specific criteria for group 1 (n.76, 47 M and 29 F) was non severe GHD (peak 3-10 μg/L), whereas for group 2 (n.33, 21 M and 12 F) normal GH secretion (peak > 10 μg/L) with IGF-1 levels <-1 SDS responsive (50% increase) to IGF-1 generation test. Therapy duration was similar in the 2 groups: 77 mo in group 1 and 69 mo in group 2. At diagnosis (group 1 vs 2) Ht-SDS was different (-2.6± 0.8 vs -3.0±0.8; p=0.03), while age (9.7±2.5 yrs vs 9.2±2.5), target Ht-SDS (-1.3±0.8 vs -1.5±0.9), bone age delay (-2.0± 0.9 vs -2.3±1.0), IGF-1 SDS (-1.7±1.3 vs -2.2±1.1) were similar.There were no differences between males and females. The percentage of subjects with a Ht gain SDS <0.5 (15 vs 9%) and >1 SDS (63 vs 79%) was similar between the 2 groups. By examining the parameters affecting Ht gain, the subjects showed similar characteristics not associated to the group of treatment, i.e. significant negative correlation with statural deficit at diagnosis (r=-0.49; p=0.0001), age at diagnosis (r=-0.20; p=0.05) and positive with duration of therapy (r=0.28; p=0.007). GH peak at diagnosis was not related to Ht gain in both groups. In the whole group and in the 2 separate groups, among Ht SDS at diagnosis, age at diagnosis and therapy duration, multiple regression analysis identified Ht deficit at diagnosis as the only parameter influencing Ht gain (R2=0.42 in the whole group, R2=0.36 in group 1, R2=0.49 in group 2).Conclusions. Short subjects with normal GH secretion but low IGF-1 levels showed a similar growth response to GH therapy as short subjects with non severe GHD. In our subjects with short stature and different type of GH secretion, degree of short stature at diagnosis seemed the major determinant for height gain during treatment.


2009 - SHORT STATURE HOMEOBOX-CONTAINING GENE AND IDIOPATHIC SHORT STATURE [Articolo su rivista]
Iughetti, Lorenzo; Appio, Petronilla; Capone, Lucia; Madeo, Simona Filomena; Predieri, Barbara; Balli, Fiorella; Forabosco, Antonino
abstract

The term idiopathic short stature (ISS) refers to patients who are short due to various unknown reasons. Although it is clear that multiple factors contribute to final height, genetic factors play a crucial role. Mutations of a human homeobox gene, short stature homeobox-containing (SHOX) gene, have been shown to be associated with the short stature phenotype in patients with Turner syndrome, most patients with Leri-Weill dyschondrosteosis and some cases of ISS. The prevalence of SHOX anomalies in subjects previously recognized as having ISS has been estimated at 2.4% in a large series of ISS individuals. This review focuses on the functional properties of the SHOX gene and its linkage to ISS.


2009 - Short-term effects of growth hormone treatment on the upper airways of non severely obese children with Prader-Willi syndrome [Articolo su rivista]
Salvatoni, A; Veronelli, E; Nosetti, L; Berini, J; de Simone, S; Iughetti, Lorenzo; Bosio, L; Chiumello, G; Grugni, G; Delù, G; Castelnuovo, P; Trifirò, G; Nespoli, L.
abstract

AIMS: The aim of this study was to establish whether short-term GH treatment causes obstructive apnea in patients with Prader-Willi syndrome and normal upper airway patency. SUBJECTS AND METHODS: We performed an observational longitudinal 6-week GH treatment study. Thirty-four non-severely obese Prader-Willi syndrome patients (20 boys, age range 0.94-11.8 yr, median 2.24 yr) entered an observational longitudinal 6-week study. Sixteen boys received recombinant human GH (rhGH) treatment; the remaining 18 represented the control group and received no treatment. Polysomnography monitoring and othorhinolaringoiatric video endoscopy were performed one night before and after 6 weeks of rhGH treatment (0.03 mg/kg body weight/day). All patients underwent auxologic assessment, fasting blood glucose, insulin and IGF-I evaluation. The main polysomnographic parameter considered was total apnea hypopnea index, consisting of two components: central apnea hypopnea index and obstructive apnea hypopnea index. All patients were free of severe or moderate upper airway obstruction when rhGH treatment began. RESULTS: After 6 weeks of rhGH therapy, obstructive apnea hypopnea index increased in 8/16 (50%), decreased in 5/16 (31%), and did not change in 3/16 (19%) patients. The changes were not statistically significant. The rhGH-treated group did not differ from the control group for the apnea hypopnea index both before and after 6 weeks of treatment. Adenoids and tonsils showed a slight increase in 1 and 2 patients on rhGH treatment, respectively, and did not change in the untreated patients.CONCLUSIONS: Our data show that short-term rhGH treatment does not cause restrictions of the upper airways in patients with Prader-Willi syndrome and normal upper airway patency.


2009 - Study of inflammations' markers and insulin resistance in obese children and adolescents with and without non-alcoholic fatty liver disease. [Abstract in Rivista]
Predieri, Barbara; Lami, Francesca; Bruzzi, Patrizia; Vellani, Giulia; L., Miglioli; S., Bellentani; F., Balli; A., Gastaldelli; Iughetti, Lorenzo
abstract

Non-alcoholic fatty liver disease (NAFLD) is a serious problem in childhood obesity; hyperglycemia and oxidant stress lead to the accumulation of advanced glycation end products (AGEs) that with their soluble forms of receptor (sRAGE) could play a role in the pathogenesis of insulin resistance (IR) and the development of NAFLD.This study was planned to investigate the relationship between the presence of steatosis with anthropometric measurements, abnormal ALT and γ-glutamyl-transferase (GGT), hyperlipidemia, IR (HOMA-IR), and sRAGE in childhood obesity with and without NAFLD.28 obese children and adolescents (20 M and 8 F; 11.9±2.77 yr.; height SDS 0.55±1.52; BMI SDS 3.11±0.55) were included in the study and were divided in Group 1 (14 with NAFLD) and Group 2 (14 no-NAFLD). sRAGE levels were determined using an ELISA kit.Group 1 had significantly higher levels of tryglicerides and GGT and significantly lower concentrations of sRAGE than Group 2.


2009 - The effect of twelve months rhGH treatment on upper airways of non severely obese children with Prader-Willi syndrome. [Abstract in Rivista]
A., Salvatoni; J., Berini; S., Di Candia; L., Nosetti; A., Luce; Iughetti, Lorenzo; G., Delù; G., Grugni; P., Castelnuovo; G., Chiumello; L., Nespoli
abstract

In a previous study we showed in 16 non-severely obese and obstructive apnoea free children with Prader-Willi Syndrome that a six weeks rhGH treatment does not significantly affect airways patency. We report here the auxological and polisomnographic results of twelve among the above children who attained 12 month of rhGH treatment.Patients and Methods: Twelve children (9 boys, aged from 1.6 to 7.7 median 2.25 yrs) with genetically confirmed Prader-Willi syndrome were studied before and after 6 weeks and 12 months of rhGH treatment. In each of the three evaluations the patients were studied by anthropometry, one night 16 channels polysomnography and ENT examination of upper airways by flexible fibreoptic endoscope. The polysomnographic parameters considered were respiratory disturbance index (RDI), obstructive apnea index (OAI) and minimal SaO2. The Katz criteria were used for polysomnography evaluation. Tonsils hypertrophy was scored from 0 to +4 according to the Brodsky criteria and adenoid hypertrophy was classified as Wang criteria. SDS BMI was calculated according to CDC standards. Non parametric Friedman test and Fisher's exact test were used for statistical analysis.Results: The main results are reported in the table. In particular we found a statistically significant reduction of RDI after 12 months of rhGH treatment and any reduction of upper airways patency in all but in one patient who required adenotonsillectomy. SDS BMI showed a slight, statistically unsignificant increase.Conclusions: The significant reduction of RDI is in agreement with previous studies showing improvement of respiratory function during GH treatment of Prader-Willi children. The important adenoids and tonsils hypertrophy observed in one of our patients during medium-term GH treatment, does not prove a GH dependency of lymphatic tissue hypetrophy, however points out the importance of a close ENT follow-up in these patients.


2009 - The impact of diabetes and celiac disease in the quality of life in children and adolescents. [Abstract in Rivista]
M., Pugliese; F., Zani; Predieri, Barbara; P., Appio; Bruzzi, Patrizia; Vellani, Giulia; A. R., Di Biase; R., Berri; F., Balli; Iughetti, Lorenzo
abstract

Our data disagree with common opinion that children with CD have a better adaptation and functioning, because the disease is generally considered less severe and less invasive than diabetes. These findings contribute significant information on the effects of pediatric chronic conditions on generic QOL from the perspectives of children and have implications for care practice. We showed the importance of HRQOL assessment and factors that impact on it, not only the severity of disease. Measurement of QOL also contributes to identify children and adolescents who might need special psychological support. It is conceivable that a immediate multidisciplinary approach to patients with T1DM can be responsible for this differences. In fact, in our clinic, care practice for children with T1DM and CD is different. The integrated multidisciplinary intervention based on family centered care, since the time of diagnosis, is only for patients with T1DM. Unfortunately, the multidisciplinary team is available for patients with CD only on advice, in particular for psychological counseling.


2008 - A new device for measuring resting energy expenditure in severely obese children and adolescents with and without non-alcoholic fatty liver disease. [Abstract in Rivista]
Predieri, Barbara; Lami, Francesca; Bruzzi, Patrizia; Vellani, Giulia; M., Dugoni; L., Miglioli; S., Bellentani; F., Balli; Iughetti, Lorenzo
abstract

The study demonstrates a NAFLD prevalence similar to data reported in literature (range 20-77%) although lower than other populations suggesting different genetic and/or environmental factors SWA is an easy to handle and practical portable device for measuring REE. However, our results demonstrate that REE SWA measurements are significantly higher than those evaluated with IC, despite a positive significant correlation between SWA and IC; this data suggest the necessity to develop new obesity-specific algorithmsAlthough SWA probably may represent an acceptable device to measure REE in obese subjects, this evaluation do not allow to distinguish between NAFLD and non-NAFLD obese patients


2008 - Adult height in children with short stature and idiopathic delayed puberty after different management. [Articolo su rivista]
Zucchini, S; Wasniewska, M; Cisternino, M; Salerno, M; Iughetti, Lorenzo; Maghnie, M; Street, Me; CARUSO NICOLETTI, M; Cianfarani, S.
abstract

By retrospectively collecting data from nine Italian centres of pediatric endocrinology, we assessed the different management and final outcome of children with short stature and idiopathic delayed puberty. Data were obtained in 77 patients (54 males, 23 females) diagnosed and followed-up in the various centres during the last 15 years. Inclusion criteria were short stature at initial observation and idiopathic delayed puberty diagnosed during follow-up. At first observation, age was 13.8 ± 1.0 years and height standard deviation score (SDS) was –2.6 ± 0.6 in males. In females age was 13.1 ± 0.9 years and height SDS –2.6 ± 0.4. Local diagnostic and therapeutic protocols included testing for growth-hormone deficiency (six centres) and treatment in case of deficiency or, in the remaining centres, testosterone or no treatment in males, and no treatment in females. At diagnosis, both in males and in females, the auxological features (height SDS, target height SDS and bone age delay) were similar in the patients treated with growth hormone, testosterone or not treated. Overall 32 patients received growth hormone (25 males, 7 females), 33 no treatment (17 males, 16 females) and 12 testosterone. There was no difference in the adult height of males and females in the different treatment groups. In males there were no differences between adult and target height SDSs (growth hormone-treated 0.31 ± 0.79, untreated 0.10 ± 0.82, testosterone-treated 0.05 ± 0.95), between adult and initial height SDSs (growth hormone-treated 1.70 ± 0.93, untreated 1.55 ± 0.92, testosterone-treated 1.53 ± 1.43) and percentage of subjects with adult height above target height. In females, there were no differences between adult and target height SDSs (growth hormone-treated –0.49 ± 1.13; untreated 0.10 ± 0.97) and between adult and initial height SDSs (growth hormone-treated 1.76 ± 0.92; untreated 1.77 ± 0.98), whereas a significantly higher percentage of patients remained below target height in the growth hormone-treated group (6/7, 85.7% vs 5/11, 31.3%) (P = 0.02). In conclusion, the diagnostic and therapeutic management of the patients with short stature and delayed puberty is different among Italian pediatric endocrinologists. Our data do not support the usefulness of growth-hormone therapy in improving adult height in subjects with short stature and delayed puberty, particularly in the female sex


2008 - Approaches to dyslipidemia treatment in children and adolescents. [Articolo su rivista]
Iughetti, Lorenzo; Predieri, Barbara; Bruzzi, Patrizia; Balli, Fiorella
abstract

Atherosclerosis represents a disease that begins in childhood, and alterations in lipid concentration play a fundamental role in the development of this condition. Children and adolescents with high cholesterol levels are more likely than their peers in the general population to present with dyslipidemia in adulthood. Precocious identification of dyslipidemias associated with premature cardiovascular disease is crucial during childhood to delay or prevent the atherosclerotic process. The National Cholesterol Education Program has established guidelines for the diagnosis and treatment of dyslipidemia during pediatric age. It has been suggested that a heart-healthy diet should begin at 2 years of age, and no adverse effects on psychological aspects, growth, pubertal development and nutritional status in children and adolescents limiting total and saturated fat intake have been demonstrated. Pharmacotherapy should be considered in children aged 10 years or older when low-density lipoprotein cholesterol concentrations remain very high despite dietary therapy, especially when multiple risk factors are present. The lipid-lowering drugs recommended for childhood and adolescence are resins and statins. The increasing use of statins is dependent on their effectiveness and safety. Ezetimibe, a selective cholesterol absorption inhibitor, may provide a similar cholesterol-lowering effect as that reached with statin treatment. This review provides an update on recent advances in the therapy of dyslipidemia, especially hypercholesterolemia, during pediatric age and adolescence.


2008 - Complex disease phenotype revealed by GH deficiency associated with a novel and unusual defect in the GH-1 gene. [Articolo su rivista]
Iughetti, Lorenzo; Sobrier, Ml; Predieri, Barbara; Netchine, I; Carani, Cesare; Bernasconi, S; Balli, Fiorella; Amselem, S.
abstract

We report a case of two Moroccan siblings (a girl and a boy) withsevere dwarfism. The parents are first cousins with normal height(father 175·1 cm, 0·06 SDS, mother 160·5,−0·28 SDS). They had three other daughters and one son, who died within the first 3 years of life, for unknown reasons. They have another living daughter of normal height for age.


2008 - Diagnosi genetica e valutazione della funzione endoteliale in adolescenti affetti da ipercolesterolemia familiare. [Abstract in Rivista]
Predieri, Barbara; Rossi, Rosario; Bruzzi, Patrizia; Nuzzo, A; Vellani, Giulia; Patianna, V; Iaccarino, D; Mazzali, E; Balli, F; Calandra, S; Modena, Maria Grazia; Iughetti, Lorenzo
abstract

Diagnosi genetica e valutazione della funzione endoteliale in adolescenti affetti da ipercolesterolemia familiare.


2008 - Endocrine and gastroenterological diseases: A frequent union? [Patologie endocrine e gastroenterologiche: Un'unione frequente?] [Relazione in Atti di Convegno]
Strocchio, L; Predieri, Barbara; Bernasconi, S; Iughetti, Lorenzo; Bozzola, M.
abstract

n.a.


2008 - Endocrine disorders and coeliac disease. [Articolo su rivista]
Iughetti, Lorenzo; Bruzzi, Patrizia; Predieri, Barbara
abstract

no abstract


2008 - Hearing loss in Turner syndrome: Results of a multicentric study [Articolo su rivista]
Bergamaschi, R; Bergonzoni, C; Mazzanti, L; Scarano, E; Mencarelli, F; Messina, F; Rosano, M; Iughetti, Lorenzo; Cicognani, A.
abstract

The purpose of this article was to evaluate otological diseases in 173 patients (pts) with Turner syndrome (TS). STUDY DESIGN: One hundred and seventy-three pts, mean chronological age (CA) 12±6.2 yr. Patients were submitted to different therapies: GH, estrogen therapy (EE), no therapy (no tx). Seventy-nine pts (CA 11 yr) had no otological diseases. Conductive hearing loss (CHL) occurred in 38.7% (CA 11 yr) and otoscopy was: persistent secretory otitis media in 55.2%, chronic otitis media in 10.4%, pars flaccida retraction pocket in 19.4%, mostly bilateral. Cholesteatoma was present in 15%. Sensorineurinal hearing loss (SNHL) occurred in 15.6% (CA 16 yr), 11 of whom were affected by high tone loss, and 15 by loss in midfrequencies (dip between 0.5-3 kHz), bilateral in 93%. Degree of hearing loss (HL) was mild [20-40 decibel hearing level (dBHL)] in 15%, moderate (45-60 dBHL) in 31%, severe (65-80 dBHL) in 8%, profound (dBHL>85) in 2%. We found a significant association between CHL and karyotype 45, X (p<0.025), congenital cranio-facial abnormalities, prevalently with low-set ears (p<0.04), narrow and/or high arched palate (p<0.018), and micrognathia (p<0.004). Our study confirms that the high prevalence of middle ear infections and CHL in TS are probably due to growth disturbances of the structures from the first and second branchial arches. We did not find any association between EE, GH, and HL. We recommend a regular audiological follow-up, especially during childhood, to prevent important middle ear anatomic sequele and to identify HL at an early stage, as the impact on social functioning may be significant.


2008 - La terapia farmacologica dell'obesità in adolescenza. [Articolo su rivista]
Tanas, R; Iughetti, Lorenzo; LA FAUCI, G; Zaghi, M; Berri, R; China, Mc; DI MAIO, S.
abstract

N.A.


2008 - La gestione del rischio clinico nelle strutture ospedaliere: l’attività di prevenzione e le responsabilità del management [Articolo su rivista]
Baraghini, G; Trevisani, B; Petrini, C; Iughetti, Lorenzo; Ganotti, S.
abstract

no abstract


2008 - Le merendine sono tutte uguali? Quale colazione per i bambini?. [Articolo su rivista]
Predieri, Barbara; Vellani, Giulia; Bruzzi, Patrizia; Lami, Francesca; Patianna, VIVIANA DORA; Garini, L; Bernasconi, S; Balli, Fiorella; Iughetti, Lorenzo
abstract

no abstract


2008 - Longitudinal study of endothelial function in children with familial hypercholesterolemia. [Abstract in Rivista]
Iughetti, Lorenzo; Predieri, Barbara; Patianna, VIVIANA DORA; Bruzzi, Patrizia; Rossi, Rosario; G., Delle Donne; F., Balli; Modena, Maria Grazia
abstract

Endothelial function (EF) is impaired in diseases associate with vascular complications, such as diabetes and familialhypercholesterolemia (FH). The impairment of EF assessed as flow mediated dilation (FMD) of brachial artery can predict futurecardiovascular disease. To assess the alteration of EF, we longitudinally evaluate FMD in prepubertal patients with geneticallyconfirmed FH. Twelve children (7 M, 5 F; 8.19±2.90 yr.) with FH and 20 control subjects entered the study. Subjects withdiabetes, obesity or other metabolic disorders were excluded. In all FH patients lipid values and FMD were determined at thebeginning of the study and after 32.8±9.55 mo. of diet low in saturated fat and cholesterol. FMD function was assessed bymeasurement of endothelium-dependent vasodilation of the brachial artery using an ultrasound system. FMD was expressed aspercentage change of diameter following reactive hyperemia from baseline. The lower FMD values obtained in our control patientwas 7% so we considered it as cut-off. The baseline evaluation showed that FMD in FH children was not significantly different thancontrol peers (20.9±23.3 vs 12.5±7.28%; p=0.143). According to sex, M were significantly older than F and had a longer followup (38.1±7.52 vs 25.5±7.09 mo.; p = 0.015). At the end of the study, despite T-CH, LDL, HDL, and TG levels were unmodified,FMD values significantly decreased (20.9±23.3 vs 2.75±9.07%; p=0.034) resulting significantly lower than in normal subjects(p=0.002). The impairment was shown in 75% vs. 25% of children found at the start. No correlation was demonstrated betweenFMD and lipid levels, age and duration of the follow-up. Our data show that after few years patients with FH have a decrease ofFMD values not apparently related to lipid control or to duration of diet. This difference, more evident in males, suggests that furtherstudies are needed to better understand which factors are involved in functional changes of endothelial dysfunction.


2008 - Low-density lipoprotein oxidizability in children with chronic renal failure [Articolo su rivista]
Iughetti, Lorenzo; Perugini, C; Predieri, Barbara; Madeo, S; Bellomo, G; Bernasconi, S; Balli, Fiorella
abstract

Background: In childhood, dyslipidemia and low-density lipoprotein (LDL) oxidation play an important role in the development of atherosclerosis. Alterations of these factors have been shown in adult uremic patients.Methods: Nine children affected by chronic renal failure (CRF; urinary tract malformation, n = 8; polycystic kidney disease, n = 1) were studied to investigate the abnormalities of plasma lipoprotein concentration and composition and to assess the susceptibility of LDL to oxidation. All patients with CRF were on conservative treatment and, after informed consent, underwent the evaluation of (i) quantitative and qualitative plasma lipid profile; (ii) lipoprotein oxidation in vitro; and (iii) lipoprotein anti-oxidant content. These results were compared to those of an age-matched control group of eight healthy children.Results: Total cholesterol, LDL and triglycerides were significantly higher in CRF than in the control group. The composition of lipoproteins was different in the two groups: the amount of anti-oxidant factors (α-, γ-tocopherol and carotenoids) was different in CRF and normal controls children, while LDL susceptibility to oxidation was significantly higher in uremic children than in controls.Conclusions: CRF patients, already before dialysis, have a higher LDL oxidizability due to an altered lipoprotein composition and a low anti-oxidant content; therefore they have higher risk factors for atherosclerosis. On the basis of these data, supplementation with anti-oxidants might be useful in CRF children, but further studies are needed to evaluate the efficacy and safety of this therapeutic intervention.


2008 - Malattia celiaca e patologie endocrine autoimmuni [Articolo su rivista]
Iughetti, Lorenzo; Bruzzi, Patrizia; Predieri, Barbara; Berri, Rossella; BI BIASE, Ar; Balli, Fiorella
abstract

RiassuntoE’ ampiamente descritta sia un’aumentata frequenza della malattia celiaca (MC) in soggetti affetti da malattie autoimmuni, sia un’aumentata prevalenza di malattie autoimmuni in soggetti affetti da MC. Bambini con patologie autoimmuni presentano un rischio 10 volte maggiore rispetto la popolazione sana di essere affetti da MC. La predisposizione genetica, le alterazioni immunologiche comuni, il ruolo degli antigeni alimentari e l’aumento della permeabilità intestinale suggeriscono una possibile spiegazione a tale associazione le cui manifestazioni cliniche sono esposte nell’articolo. Autoimmunity diseases are known to be associated with celiac disease (MC). Children with autoimmune disease have a risk 10 fold higher than general population to be affected from MC. Genetic predisposition, immunological pathways, environmental factors as food antigens and an increased gut permeability may explain that association


2008 - Malattia celiaca, una rivisitazione patogenetica e clinica. [Articolo su rivista]
Iughetti, Lorenzo; Bruzzi, Patrizia; Predieri, Barbara; BI BIASE, Ar; Balli, Fiorella
abstract

RiassuntoLa malattia celiaca (MC) èun’enteropatia acquisita,permanente, a eziologiamultifattoriale, che insorgein soggetti geneticamentepredisposti. Il danno allamucosa del piccolo intestinoè causato da una reazioneimmunitaria reattivaall’esposizione di glutine. Laceliachia si può manifestarein molti modi diversi. Oggil’attenzione alle possibilimanifestazioni extraintestinali diMC porta al riconoscimento dimolti più casi che in passato.SummaryCeliac disease (MC) is a lifelongintestinal disorder, found inindividuals who are geneticallysusceptible. Damage to themucosal surface of the smallintestine is caused by animmunologically toxic reactionto the exposition to gluten.Celiac disease affects peopledifferently. Many symptomaticpatients with newly diagnosedMC initially present with nongastrointestinal manifestations.


2008 - Metabolic syndrome in children and adolescents with Prader-Willi syndrome: Preliminary results. [Abstract in Rivista]
G., Grugni; M., Cappa; A., Corrias; A., Crinò; L., Gargantini; Iughetti, Lorenzo; L., Ragusa; A., Salvatoni; P., Brambilla
abstract

The paper shows the presence of a significant prevalence of Metabolic syndrome in children and adolescents with Prader-Willi syndrome


2008 - Obesity in adolescence: Its prevention and psycho-social aspects [Prevenzione e aspetti psico-sociali dell'obesità in età evolutiva] [Articolo su rivista]
Iughetti, Lorenzo; Bruzzi, Patrizia; Predieri, Barbara; Vellani, Giulia; Balli, F.
abstract

Obesity is the most frequent nutritional disorder in adolescence and the rapid rise in its prevalence is one of the most alarming public health issue that western countries have to face nowadays. Directly associated with the rise in adolescence obesity is an increase in the prevalence of weight-related medical problems such as type 2 diabetes and metabolic syndrome. Therefore, obese adolescents might even be the first generation to die before their parents. Interventions that target risk factors for obesity at the individual, family and community levels are needed in order to prevent its increasing prevalence. Being adolescence not only one of the most vulnerable periods for the development of obesity but also the most important formative period in life, youth is a priority population for intervention strategies on both food behaviour and physical activity.


2008 - Pituitary height and neuroradiological alterations in patients with Prader-Labhart-Willi syndrome. [Articolo su rivista]
Iughetti, Lorenzo; Bosio, L; Corrias, A; Gargantini, L; Ragusa, L; Livieri, C; Predieri, Barbara; Bruzzi, Patrizia; Caselli, G; Grugni, G.
abstract

Prader-Willi syndrome (PWS), a genetic disorder due to an alteration in the paternally derived long arm of chromosome 15, is characterized by a complex clinical picture (short stature, obesity, hypogonadism) that seems to be referable to as a central hypothalamic/pituitary dysfunction. To determine whether there is any diminution in the anterior pituitary gland or other neuroradiological alterations, we retrospectively analysed 91 patients with PWS (42 females, 49 males; age range: 0.7–16.8 years) by cerebral magnetic resonance imaging (MRI). Of these 91 patients, MRI analysis showed a reduction in pituitary height in 45 patients (49.4%), a complete absence of the posterior pituitary bright spot in six patients (6.6%) and other neuroradiological alterations in ten patients (11%). Altogether, neuroradiological alterations were present in 61 of the 91 (67%) patients. Our results indicate that neuroradiological alterations are more frequent in PWS patients than has been reported to date


2008 - Prevenzione e aspetti psico-sociali dell’obesità in età evolutiva. [Articolo su rivista]
Iughetti, Lorenzo; Bruzzi, Patrizia; Vellani, Giulia; Predieri, Barbara; F., Balli
abstract

N.A.


2008 - Response to GH therapy in short children with normal GH secretion and low IGF-I levels. [Abstract in Rivista]
S., Zucchini; M., Caruso Nicoletti; M., Maghnie; A., Marsciani; Iughetti, Lorenzo; Predieri, Barbara; M. E. Street, S. i; L., Ghizzoni
abstract

The paper shows the response to GH therapy in short children with normal GH secretion and low IGF-I levels.


2008 - The Italian national survey for Prader-Willi syndrome: An epidemiologic study [Articolo su rivista]
Grugni, G; Crinò, A; Bosio, L; Corrias, A; Cuttini, M; DE TONI, T; DI BATTISTA, E; Franzese, A; Gargantini, L; Greggio, N; Iughetti, Lorenzo; Livieri, C; Naselli, A; Pagano, C; Pozzan, G; Ragusa, L; Salvatoni, A; Trifirò, G; Beccaria, L; Bellizzi, M; Bellone, J; Brunani, A; Cappa, M; Caselli, G; Cerioni, V; Delvecchio, M; Giardino, D; Iannì, F; Memo, L; Pilotta, A; Pomara, C; Radetti, G; Sacco, M; Sanzari, A; Sartorio, A; Tonini, G; Vettor, R; Zaglia, F; Chiumello, G; GENETIC OBESITY STUDY GROUP OF ITALIAN SOCIETY OF PEDIATRIC ENDOCRINOLOGY AND DIABETOLOGY, Isped
abstract

Twenty-five medical centers and the Prader-Willi Syndrome (PWS) Association collaborated on a study which attempted to identify all people with genetically confirmed diagnosis of PWS living in Italy. Investigators of the participating centers contacted PWS subjects and/or their family, filled in a specially developed form with the required data and forwarded this information by email. The study identified 425 subjects (209 males and 216 females, between the ages of 0.4-46.7). Two hundred thirty-eight patients had del15, 104 had UPD15, 4 demonstrated a translocation affecting chromosome 15 and 79 showed a positive methylation test. There were fewer subjects found over the age of 35, probably due to the low rate of identification of older PWS patients as well as the high mortality rate. There were a greater number of male children and adolescents with PWS whilst, amongst adults, there were more females. As expected, the majority of subjects with PWS were obese, especially in adult life. Nevertheless, it is noteworthy that 26% of patients aged between 6 and 17 were normal weight. A total of 212 subjects had received GH treatment, of which 141 were still receiving therapy, while the remaining 71 had stopped. In children and adolescents (233 cases), 89 subjects had never undergone GH therapy. Eighteen PWS patients had died in the past 20 years. Obesity-related cardiovascular and respiratory diseases were the cause of death, both during childhood and after 18 years of age. Three children died suddenly whilst undergoing GH therapy. Respiratory infection and cardiac illness were the causes of death in two cases. There was no definitive cause of death found in the third case. Overall, there was no increase in number of deaths during GH treatment, suggesting that GH administration in patients with PWS, as a group, does not increase the risk of death


2008 - Thirty-year persistence of obesity after presentation to a pediatric obesity clinic. [Articolo su rivista]
Iughetti, Lorenzo; DE SIMONE, M; Verrotti, A; Iezzi, Ml; Predieri, Barbara; Bruzzi, P; Bernasconi, S; Balli, Fiorella; Bedogni, G.
abstract

BACKGROUND: Few large, long-term studies are available on the relationship between childhood and adult obesity. AIM: The present study examined the 30-year association between childhood and adult obesity in a large sample of girls with essential and uncomplicated obesity. SUBJECTS AND METHODS: 318 girls who had visited our Pediatric Obesity Clinic between January 1972 and December 1974 were re-contacted between January 2002 and December 2005. All had undergone an assessment of weight, height and pubertal status at the baseline visit. Anthropometry was performed again on those who agreed to take part in the follow-up visit. The women's general practitioners were also asked to compile a health questionnaire. Hypertension, hypercholesterolemia, hypertriglyceridemia and diabetes were defined according to current guidelines. Rates are expressed as number of cases per 1000 person-years (PY). Multivariable Poisson regression was used to identify predictors of persistent obesity. RESULTS: 224 (70%) of the 318 girls took part to the 30-year follow-up study. They had the same baseline anthropometry of those not available at follow-up. Sixteen per cent of them were still obese at the 30-year follow-up, giving a persistence rate of obesity of 5.2 x 1000 PY. Tanner stages > or = 1 [rate = ratios (RR) from 4.73 to 7.74 for different stages, p < or = 0.021] and Z-score of BMI (RR = 2.72 for one SDS, p = 0.019) were independent predictors of obesity persistence. Having a university degree vs. an elementary degree was instead protective (RR = 0.32, p = 0.009). The most prevalent complication was hypertriglyceridemia (8.8 x 1000 PY), followed by hypercholesterolemia (rate = 8.4 x 1000 PY), hypertension (rate = 5.2 x 1000 PY) and diabetes mellitus (rate = 1.0 x 1000 PY). CONCLUSION: The study reinforces the notion that obesity should be prevented at an early age and shows that adolescents with severe obesity and low educational degree are at greater risk of becoming obese adults.


2008 - Triplication of SHOX gene in a boy with short stature. [Abstract in Rivista]
Iughetti, Lorenzo; L., Capone; H., Elsedfy; M., Rashad; R., Bertorelli; Predieri, Barbara; Patianna, VIVIANA DORA; M., El Kholy
abstract

The assessment that heterozygous SHOX mutations leading to SHOX haploinsufficiency play a role in subjects with idiopathic short stature (ISS) is already documented in literature as well as the suggestion that additional copies of SHOX are strongly implicated in a condition of tall stature. However, we report the first case of short stature in a male associated with the presence of 3 copies of SHOX gene.Through a chromosome analysis, using Multiplex Ligation-dependent Probe Amplification method of SHOX salsa P018B kit and microsatellites analysis, we identify a new interstitial isolated duplication of the SHOX gene and its enhancer caused by a larger duplication of PAR1 region in a ISS boy. Consequently, we form the hypothesis that this chromosome re-arrangement disrupts the regular interaction between enhancer and promoter, resulting in a transcription block and determining a lack of gene activation and causes the clinical feature of short stature.


2008 - Type 1 Diabetes Mellitus in African population: epidemiology and management challenges. [Articolo su rivista]
Majaliwa, E; Elusiyan, J; Adesiyun, O; Laigong, P; Adeniran, K; Kandi, C; Yarhere, I; Limbe, M; Iughetti, Lorenzo
abstract

Type 1 Diabetes Mellitus (T1DM) is a growing concern worldwide; while there has been a greatimprovement in the knowledge, epidemiology and management of this condition in the developed worlds,there has been little or no improvement in sub-Saharan Africa. The true burden of this disease is not evenknown, but a difference in the pattern and outcome of T1DM in the sub-Saharan Africa compared to thewestern World seems to be present. Moreover, much of the available data is not population-based and is oflimited value for making generalizations about Diabetes in children of Sub-Saharan Africa. Despite the limitations,there is evidence that these populations may be important for studying the aetiology and natural historyof Type 1 diabetes. Effective management and/or prevention of diabetes and its complications in Sub-Saharan African children should adopt multidisciplinary approaches. In order to improve care for diabetespatients in developing countries, specialized clinics need to be established. (www.actabiomedica.it)


2008 - Unforgettable cases in pediatric general practice: HyperCPKemia (high creatine phosphokinase blood levels), not just myopathy [IperCPKemia, non solo miopatie] [Articolo su rivista]
Quitadamo, Al; Pellicanò, Fa; Predieri, Barbara; Bruzzi, Patrizia; Vellani, Giulia; Madeo, Simona Filomena; Iughetti, Lorenzo
abstract

n.a.


2007 - Basi genetiche ed aspetti terapeutici delle ipercolesterolemie familiari [Articolo su rivista]
Iughetti, Lorenzo; Bruzzi, Patrizia; Vellani, Giulia; Predieri, Barbara; Patianna, VIVIANA DORA; Balli, Fiorella
abstract

Atherosclerosis represents a disease that begins in childhood and low-density lipo-protein cholesterol plays a pivotal role for the development of this pathology. Children and adolescents with highcholesterol levels are more likely, than their peers, to present cholesterol elevation as adults. The identification of genetic dyslipidemias associated with premature cardiovasculardisease is crucial during childhood in order to delay or prevent the atherosclerotic process. Guidelines for the diagnosis and treatment of hypercholesterolemia during pediatric age are available from the National Cholesterol Education Program. A heart-healthy diet limiting rotaiand saturated fat intake should begin at age 2 years and a large number of studies have demonstrated no adverse effects on nutritional status, growth, pubertal development and psychological aspects in children and adolescents. Pharmaco- therapy should be considered in children over l0 years of age when low-density lipoprotein cholesterol concentrations remain very high despite severe dietary therapy, especially when multiple riskFactors are present the only lipid-lowering drugs recommended until now for childhood and adolescence are the resins which although have been reported to be effective and well tolerated, have shown to be associated with very poor compliance because of unpalatability. The use of statins is increasing and seems to be effective and sale in children, even if current studies have enrolled only a small number of patients and evaluated efficacy and safety (for short-term follow-up). Recently, a new drug, ezetimibe, seems to be efficacious and is synergic to the cholesterol-lowering therapeutic effects of statins. This review provides an update on recent advances in the diagnosis, therapy, and follow-up of familial hypercholesterolemia during pediatric age and adolescence.


2007 - Deficit di ormone della crescita e malattia celiaca. [Capitolo/Saggio]
Iughetti, Lorenzo; F., Pellicanò; Vellani, Giulia; Predieri, Barbara
abstract

N.A


2007 - Deficit di ormone della crescita (GH) di origine genetica [Capitolo/Saggio]
Iughetti, Lorenzo; P., Appio; Vellani, Giulia; E., Garetti; S., Cattani; P. L., Ceccarelli; Predieri, Barbara
abstract

N.A.


2007 - Diagnosi e follow-up di un caso di iperinsulinismo congenito. [Capitolo/Saggio]
Iughetti, Lorenzo; P., Appio; Vellani, Giulia; E., Garetti; S., Cattani; P. L., Ceccarelli; Predieri, Barbara
abstract

N.A.


2007 - Due fratelli uniti da un unico destino? [Relazione in Atti di Convegno]
Mariotti, I; Garetti, E; Roversi, Mf; Della Casa, E; Fiorini, V; Pagano, R; Baroni, L; Dotti, D; Ori, L; Predieri, Barbara; Iughetti, Lorenzo; Ferrari, Fabrizio
abstract

No abstract


2007 - Endothelial function in children with type 1 diabetes mellitus: a longitudinal study. [Abstract in Rivista]
Iughetti, Lorenzo; Predieri, Barbara; D., Iaccarino; S., Madeo; A. L., Quitadamo; G., Delle Donne; Bruzzi, Patrizia; F., Balli; Rossi, Rosario; Modena, Maria Grazia
abstract

n.a.


2007 - Evaluation of insulin resistance in children and adolescent with moderate and severe obesity. [Abstract in Rivista]
Predieri, Barbara; S., Madeo; A. L., Quitadamo; F., Pellicanò; Vellani, Giulia; F., Balli; S., Bernasconi; Iughetti, Lorenzo
abstract

The global increase of obesity in children and adolescents is the main risk factor associated with development of insulin resistance and type 2 diabetes mellitus. Several indices have been published to quantify insulin sensitivity from data obtained by the oral glucose tolerance test (OGTT).The aim of our study was to evaluate the influence of body composition on different indices of insulin sensitivity (ISI) in obese children and adolescents.A total of 292 subjects (161 boys and 131 girls aged 10.4±2.66 years; BMI 29.6±4.32 kg/m2) underwent a standard OGTT. The patients were divided into groups with moderate obesity (Group A = BMI SDS between 2 and 2.5) and severe obesity (Group B = BMI SDS > 2.5). ISI were calculated from plasma glucose and insulin concentrations using HOMA-IR, QUICKI, Cederholm, Matsuda, and Stumvoll.There was a significant (p<0.05) negative correlation between QUICKI, ISI Cederholm, ISI Matsuda, ISI Stumvoll and BMI SDS (r = -0.129, r = -0.128, r = -0.136, and r = -0.153, respectively). No correlation was demonstrated between BMI SDS and HOMA-IR. The ISI were all significantly different between Group A and Group B. In the Group B the ISI QUICKI, Cederholm, Matsuda, and Stumvoll were significantly lower while HOMA-IR resulted higher (Table 1).In our study indexes of insulin sensitivity derived from OGTT correlate strongly with BMI SDS and were significantly impaired in severe obesity. Our data confirm that already in childhood overweight is one of the most important factor for the development of insulin resistance. However, further studies are needed to establish appropriate cut-off values to use for clinical practice.


2007 - Ginecomastia dell'adolescente: liposcultura e mastoplastica riduttiva round-block [Relazione in Atti di Convegno]
D., Biondini; Pl, Ceccarelli; M., Pinelli; Iughetti, Lorenzo; Predieri, Barbara; Cacciari, Alfredo
abstract

non disponibile


2007 - High basal serum allopregnanolone levels in overweight girls [Articolo su rivista]
Predieri, Barbara; Luisi, S; Casarosa, E; De Simone, M; Balli, Fiorella; Bernasconi, S; Rossi, M; Petraglia, F; Iughetti, Lorenzo
abstract

Objective: Several studies demonstrated that obese subjects have a hyperactive hypothalamic-pituitary-adrenal axis and that sex steroid hormones have been closely related to the regulation of adiposity, either through direct or indirect physiological mechanisms. Allopregnanolone (3 alpha-hydroxy-5 alpha-pregn-20-one; AP) is a circulating neuroactive steroid hormone involved in the modulation of behavioral functions, stress and neuroendocrine axis. The aim of our study was to evaluate basal serum AP levels in obese children. Subjects and measurements: We studied 27 normal weight ( NW) and 23 overweight (OW) girls. Gonadotropins and steroid hormones were assessed in all patients. Results: Basal AP concentrations in OW girls were significantly higher than in NW controls (P = 0.013). There was no difference found between the other gonadal and adrenal hormones. Considering the pubertal stage, we demonstrated that obese pubertal girls presented higher AP concentrations than prepubertal and pubertal NW ones ( P = 0.020), and higher dehydroepiandrosterone sulfate (DHEAS) levels with respect to prepubertal obese girls, and prepubertal and pubertal NW patients ( P = 0.025). AP and DHEAS were significantly directly related to weight (r = 0.31 and r = 0.54, respectively) and body mass index ( r = 0.29 and r = 0.34, respectively). In pubertal OW girls, a significant positive correlation between AP and DHEAS ( r = 0.60), A ( r = 0.72) and luteinizing hormone ( r = 0.64) levels was demonstrated. Conclusion: The present study demonstrates that AP is hypersecreted in children and adolescent with OW involving DHEAS concentrations, too. Our data suggest a possible role of AP in the regulation of neuroendocrine axis related to obesity. We can also speculate that in OW girls, who could manifest emotional and behavioral problems, a part of higher levels of this neuroactive steroid might act as gamma-aminobutyric acid agonist producing anxiolytic-sedative effects.


2007 - Iper CPKemia, non solo miopatie [Relazione in Atti di Convegno]
A. L., Quitadamo; F., Pellicanò; Predieri, Barbara; Bruzzi, Patrizia; Vellani, Giulia; S., Madeo; Iughetti, Lorenzo
abstract

N.A.


2007 - Ipercolesterolemia familiare omozigote. [Capitolo/Saggio]
Iughetti, Lorenzo; P., Appio; G., Vellani; E., Garetti; S., Cattani; P. L., Ceccarelli; Predieri, Barbara
abstract

N.A.


2007 - IperCPKemia e tiroidite linfocitaria. [Capitolo/Saggio]
Iughetti, Lorenzo; F., Pellicanò; Vellani, Giulia; Predieri, Barbara
abstract

N.A.


2007 - La sindrome di Prader Willi. [Articolo su rivista]
Taruscio, D; Koldra, Y; Censi, F; Bernasconi, S; Crinò, A; Gargantini, L; Grugni, G; Iughetti, Lorenzo; Ragusa, L; Ricci, Am
abstract

no abstract


2007 - L’ipercolesterolemia familiare: terapia farmacologica [Articolo su rivista]
Iughetti, Lorenzo; Predieri, Barbara; Bruzzi, Patrizia; Vellani, Giulia; F., Balli
abstract

Nei casi di dislipidemia d’origine genetica, spesso associati a gravi quadri di morbilità e mortalità cardio-vascolari già in giovane età, la diagnosi e il trattamento precoci risultano cruciali per prevenire o ritardare le complicanze. a dieta, povera di grassi saturi e di colesterolo, deve essere considerata il primo approccio terapeutico nei bambini di età superiore ai 2 anni con ipercolesterolemia ; essa garantisce infatti il mantenimento di un apporto nutrizionale adeguato alla crescita e al regolare sviluppo puberale. Si consiglia di limitare l’uso dei farmaci ipocolesterolemizzanti ai pazienti di età superiore ai 10 anni in cui la dieta, seppur severa, non sia efficace, soprattutto se sono presenti più fattori di rischio cardiovascolari. Ad oggi, tra tutti i farmaci ipocolesterolemizzanti, solo le resine sequestranti acidi biliari sono raccomandate nell’infanzia e nell’adolescenza. La loro scarsa palatibilità limita la compliance alla terapia in età pediatrica. Sempre maggiore è l’interesse verso le statine. Gli studi presenti in letteratura sull’efficacia e la sicurezza delle statine in pediatria danno risultati positivi, seppur condotti su casistiche limitate e prendendo in esame solo gli effetti avversi a breve termine. Recentemente un nuovo farmaco, ezetimibe, sembra efficace e sinergico all’attività terapeutica delle statine. Questa revisione si propone di segnalare le più recenti acquisizioni sulla diagnosi, la terapia e il follow-up dell’ipercolesterolemia familiare in età pediatrica.


2007 - Lipid profile and antioxidant status in children and adolescents with type 1 diabetes mellitus. [Abstract in Rivista]
Iughetti, Lorenzo; Predieri, Barbara; S., Madeo; A. L., Quitadamo; A., Lasagni; S., Bernasconi; F., Balli
abstract

Type 1 diabetes mellitus (T1DM) is associated with the development of micro- and macro-vascular complication generally related to duration of disease, poor glycemic control and lipid abnormalities. Chronic hyper-glycemia increases production of free radical intermediates which in turn augments oxidative stress. The oxidative stress plays a key role in the development of diabetic complications. In the present study we evaluated the lipid profile, the parameters related to oxidative stress, and the relationships ofthese parameters with metabolic control of disease in children and adolescents with T1DM. A total of 58 T1DM patients(11.5±3.49 yr) were studied, matched for age and sex with 36 healthy subjects (9.60±3.21 yr). In all children serum concentration of total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglycerides (TG), lipoprotein(a) (Lp(a)), homocysteine, fibrinogen, MDA, vitamin E (Vit. E), β-carotene, lycopene, retinol, vitamin C reduced(Vit. C-Red) and oxidized (Vit. C-Ox) were measured. There were no significant different in the levels of TC, LDL-C, and HDL-C between T1DM patients and controls. Serum concentrations of TG in T1DM subjects were significantly lower than in control ones.No significant difference of total antioxidant status (Vit. E, β-carotene, lycopene, retinol, Vit. C-Red) was demonstrated between T1DM and control groups. Serum levels of Vit. C-Ox were significant higher in patients with T1DM. Moreover,prepubertal T1DM subjects showed higher MDA serum concentrations than controls (p<0.01). In our T1DM patients the satisfactory glycemic control was coupled with normal lipid profile and normal antioxidant levels. These data confirm that an optimal dietary intervention is able to contrast oxidative processes, even if a more attention to diet composition is needed in some T1DM children and adolescentS.


2007 - Longitudinal study of endothelial function in children with type 1 diabetes mellitus [Abstract in Rivista]
Iughetti, Lorenzo; Predieri, Barbara; S., Madeo; A. L., Quitadamo; Bruzzi, Patrizia; G., Delle Donne; D., Iaccarino; Modena, Maria Grazia
abstract

Patients with type 1 diabetes (T1DM) have increased risk of vascular complications which development is related to the duration of diabetes and the degree of glycemic control. Impaired flow-mediated dilation (FMD) has been detected in children with diabetes, and we previously reported that a good glycemic control gets a better vascular function.Aim of our study was to evaluate longitudinally changes of FMD in T1DM patients.Thirty two children (18 male, 14 female; 11.6±3.33 yr.) with T1DM (duration of disease 49.1±39.5 months) entered the study; lipid profile, HbA1c and FMD were determined at the beginning and after 30.3±7.42 months. Vascular function was assessed by measurements of endothelium-dependent vasodilation of the brachial artery using high-sensibility ultrasound system. FMD was expressed as percentage change of diameter following reactive hyperemia from baseline.No significantly change of HbA1c (7.99±1.06 vs 8.12±1.11%; p=0.28) and FMD (6.41±10.6 vs 2.57±9.01%; p=0.09) was demonstrated; however, half of the children had FMD <7% while at the follow-up abnormal FMD was demonstrated in 75% of cases. No correlation was demonstrated between FMD and lipid profile, HbA1C or duration of the disease. Considering the glycemic control during follow-up, no difference was shown in FMD values between children with poor (>8%) and good HbA1c (≤8%) (2.69±8.55 vs 2.33±10.2%; p=0.91), despite significantly difference in the months from diagnosis (91.6±42.7 vs 56.2±26.1 months; p=0.01). According to sex, no difference of age, months of disease, HbA1c and FMD was revealed, while longitudinally boys had significantly lower FMD than girls (-0.95±8.15 vs 7.10±8.19%; p=0.009).Our data show that after several years patients had a worse FMD not apparently related to glycemic control or to duration of T1DM. This difference, more evident in males, suggests that further studies are needed to better understand which factors are involved in functional changes of endothelial dysfunction.


2007 - Melanocortin-4-receptor molecular screening in a group of phenotipically selected obese children: report of two new mutations and lack of association to the early onset of the disease [Abstract in Rivista]
Sartorio, N; Cirillo, G; Romano, T; Ciapaldo, A; Iughetti, Lorenzo; Miraglia del Giudice, E.
abstract

Background: Melanocortin-4-receptor (MC4R) mutations represent the most frequent geneticcause of non-syndromic early onset obesity. Children carrying MC4R mutations seem to show aparticular phenotype characterized by early onset, severe obesity and high stature. To verifywhether MC4R mutations are associated with this particular phenotype in the Italian pediatricpopulation, we decided to screen the MC4R gene in a group of obese children selected on the basisof their phenotype.Methods: to perform this study, a multicentric approach was designed. Particularly, to be enrolledin the study subjects needed to meet the following criteria: Body mass index ≥ 3 deviation scoresaccording to age and sex, familiar history of obesity (at least one parent obese), obesity onset beforethe 10 years old, height ≥ 2 deviation scores. The coding region of MC4R gene was screened in 240obese children (mean age 8.3±3.1, mean BMI 30.8 ± 5.4) and in 200 controls (mean age 8.1± 2.8;mean BMI 14.2 ± 2.5).Results: three mutations have been found in five obese children. The S127L (C380T), found inthree unrelated children, had been described and functionally characterized previously. The Q307X(C919T) and the Y332H (T994C) mutations were found in two patients. Functional studies showedthat only Q307X impaired protein function.Conclusions: the low prevalence of MC4R mutations (1.6%) in this group of obese childrenselected according to the obesity degree, the tall stature and the family history of obesity wassimilar to the prevalence observed in previous screenings performed in obese adults and in notphenotypically selected obese children.


2007 - Menstrual cycle pattern during the first gynaecological years in girls with precocious puberty following gonadotropin-releasing hormone analogue treatment [Articolo su rivista]
Arrigo, T; De Luca, F; Antoniazzi, F; Galluzzi, F; Iughetti, Lorenzo; Pasquino, Am; Salerno, Mc; Marseglia, L; Crisafulli, G.
abstract

no abstract


2007 - Non sempre siamo quello che mangiamo [Abstract in Atti di Convegno]
F., Pellicanò; A. L., Quitadamo; Predieri, Barbara; Bruzzi, Patrizia; Vellani, Giulia; S., Madeo; Iughetti, Lorenzo
abstract

N.A.


2007 - Prevalence of obesity in children and adolescents with Prader-Willi sindrome [Abstract in Rivista]
G., Grugni; A., Crinò; L., Bosio; A., Corrias; T., De Toni T; E., Di Battista; A., Franzese; L., Gargantini; N., Greggio; Iughetti, Lorenzo; C., Livieri; A., Naselli; G., Pozzan; L., Ragusa; A., Salvatoni; A., Sartorio; G., Trifirò; G., Chiumello
abstract

The paper shows the data related to the prevalence of obesity in children and adolescents with Prader-Willi sindrome


2007 - Prevenzione dell’obesità in età evolutiva. [Capitolo/Saggio]
Iughetti, Lorenzo; G., Vellani; S., Bernasconi; F., Balli
abstract

n.a.


2007 - Rational approach to the treatment for heterozygous familial hypercholesterolemia in childhood and adolescence: A review [Articolo su rivista]
Iughetti, Lorenzo; Predieri, Barbara; Balli, Fiorella; Calandra, S.
abstract

Atherosclerosis represents a disease that begins in childhood and in which LDL cholesterol plays a pivotal role for the development of the pathology. Children and adolescents with high cholesterol levels are more likely than their peers to present cholesterol elevation as adults. The identification of genetic dyslipidemias associated with premature cardiovascular disease is crucial during childhood to delay or prevent the atherosclerotic process. Guidelines for the diagnosis and treatment of hypercholesterolemia during pediatric age are available from the National Cholesterol Education Program. A heart-healthy diet should begin at the age of 2 yr and a large number of studies have demonstrated no adverse effects on nutritional status, growth, pubertal development, and psychological aspects in children and adolescents limiting total and saturated fat intake. Pharmacotherapy should be considered in children over 10 yr of age when LDL cholesterol concentrations remain very high despite severe dietary therapy, especially when multiple risk factors are present. The only lipid-lowering drugs recommended up to now for childhood and adolescence are resins reported to be effective and well tolerated, although compliance is very poor because of unpalatability. The use of statins is increasing and seems to be effective and safe in children, even if studies enrolled a small number of patients and evaluated efficacy and safety for short-term periods. Recently, an interesting drug represented by ezetimibe has been found that may provide cholesterol-lowering additive to that reached with statin treatment. This review provides an update on recent advances in the diagnosis, therapy, and follow-up of familial hypercholesterolemia during pediatric age and adolescence


2007 - Se il cuore decelera... [Relazione in Atti di Convegno]
Paltrinieri, Al; Gargano, G; Gallo, C; Rivi, C; Fiorini, V; Sabbioni, F; Sala, B; Bonvicini, C; Guidotti, I; Predieri, Barbara; Iughetti, Lorenzo; Ferrari, Fabrizio
abstract

No abstract


2007 - Short-term effect of rhGH treatment in children with Prader-Labhart-Willi sindrome on respiratory function: a polysomnographic and ENT endoscopic study [Abstract in Rivista]
A., Salvatoni; E., Veronellii; L., Nosetti; S., de Simone S; Iughetti, Lorenzo; L., Bosio; G., Chiumello; G., Delù; L., Nespoli
abstract

Background: Although significant improvement of respiratory function has been reported during rhGH treatment of Prader-Labhart-Willi Syndrome (PLWS), in the last five years several cases of sudden death during the first 6 months of GH therapy were reported in literature. Objectives and hypotheses: to establish if a short-term GH treatment causes obstructive apnea in PWLS patients with normal upper airways patency. Population and/or methods: 12 patients (6 boys , aged 3.9±1.9 years) were studied by one night polysomnography (PSG) monitoring (Grass 4.2) and ENT video endoscopic before and after six weeks of rhGH treatment (0.03mg/kg b.w./day). All patients underwent auxologic assessment including height, weight, BIA and plicometry, fasting blood glucose, insulin and IGF1 evaluation. The main PSG parameter considered was total apnea hypopnea index (AHI), resulting from two components: central apnea hypopnea index (CI) and obstructive apnea hypopnea index (OI). All patients were normal weight and free of severe or moderate upper airways obstruction (such as adenoid/tonsil hypertrophy, nasal obstruction with or without respiratory tract infection) when started GH treatment. Results: Statistically unsignificant changes of PSG indexes were observed after six weeks of GH therapy (see Table). We didn’t find any statistically significantly correlation between body fat, IGF1 and insulin and PSG changing during GH treatment. Video endoscopic ENT evaluation didn’t showed any significant increase of tonsillar and adenoid size after GH treatment. Precise conclusions: Our data confirm previous studies (Miller et al., JCEM, 2006; Festen et al. JCEM 2006) showing that GH treatment doesn’t cause obstructive apnea in PWLS patients with normal upper airways patency.


2007 - The treatment with continuous subcutaneous insulin infusion in Emilia Romagna. [Abstract in Rivista]
Iughetti, Lorenzo; S., Zucchini; G., Chiari; S., Cantoni; Predieri, Barbara; T., Suprani; L., Tarchini; P., Bruzzi; S., Salardi
abstract

The paper shows the increased use of CSII in Italian patients with T1DM


2007 - Uno strano caso di …irsutismo [Relazione in Atti di Convegno]
Bruzzi, Patrizia; F., Vaienti; S., Madeo; Predieri, Barbara; A. L., Quitadamo; F., Pellicanò; F., Balli; Iughetti, Lorenzo
abstract

N.A.


2006 - Assesment of serum IGF-I concentrations in the diagnosis of isolated childhood-onset GH deficiency: A proposal of the Italian Society for Pediatric Endocrinology and Diabetes (SIEDP/ISPED) [Articolo su rivista]
Federico, G.; Street, M. E.; Maghnie, M.; Caruso-Nicoletti, M.; Loche, S.; Bertelloni, S.; Cianfarani, S.; Cicognani, A.; Cesaretti, G.; Lorini, R.; Meschi, F.; de Sanctis, V.; Aimarretti, G.; Antoniazzi, F.; Arrigo, T.; Bellone, J.; Bellone, S.; Bertalloni, S.; Bozzola, M.; Buzi, F.; Cappa, M.; Cistemino, M.; De Luca, F.; Del Vecchio, M.; Galluzzi, F.; Germani, D.; Ghirri, P.; Ghizzoni, L.; Greggio, N. A.; Iughetti, L.; Losi, S.; Luciano, A.; Maffeis, C.; Modestini, E.; Pirazzoli, P.; Pozzobon, G.; Predieri, B.; Rusconi, R.; Slerno, M. C.; Salvatoni, A.; Scirè, G.; Scommegna, S.; Spadoni, G. L.; Sposito, M.; Wasniewska, M.; Zampolli, M.; Zucchini, S.
abstract

The diagnosis of GH deficiency (GHD) is based on the measurement of peak GH responses to pharmacological stimuli. Pharmacological stimuli, however, lack precision, accuracy, are not reproducible, are invasive, non-physiological and some may even be hazardous. Furthermore, different GH commercial assays used to measure GH in serum yield results that may differ considerably. In contrast to GH, IGF-I can be measured on a single, randomly-obtained blood sample. A review of the available data indicates that IGF-I measurement in the diagnosis of childhood-onset isolated GHD has a specificity of up to 100%, with a sensitivity ranging from about 70 to 90%. We suggest an algorithm in which circulating levels of IGF-I together with the evaluation of auxological data, such as growth rate and growth, may be used to assess the likelihood of GHD in pre-pubertal children.


2006 - Crescita e malattia celiaca [Articolo su rivista]
Iughetti, Lorenzo; Bruzzi, Patrizia; Predieri, Barbara; DI BIASE, R; Balli, Fiorella
abstract

no abstract


2006 - Defin