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Barbara PREDIERI

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

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Pubblicazioni

2024 - Glucometrics and device satisfaction in children and adolescents with type 1 diabetes using different treatment modalities: A multicenter real-world observational study [Articolo su rivista]
Cherubini, Valentino; Fargalli, Andrea; Arnaldi, Claudia; Bassi, Marta; Bonfanti, Riccardo; Patrizia Bracciolini, Giulia; Cardella, Francesca; Dal Bo, Sara; Delvecchio, Maurizio; Di Candia, Francesca; Franceschi, Roberto; Maria Galassi, Sabrina; Gallo, Francesco; Graziani, Vanna; Iannilli, Antonio; Mameli, Chiara; Marigliano, Marco; Minuto, Nicola; Monti, Sara; Mozzillo, Enza; Pascarella, Filomena; Predieri, Barbara; Rabbone, Ivana; Roppolo, Rosalia; Schiaffini, Riccardo; Tiberi, Valentina; Tinti, Davide; Toni, Sonia; Scaramuzza, Andrea; Vestrucci, Benedetta; Gesuita, Rosaria
abstract

Aims: To analyze metabolic outcomes, diabetes impact and device satisfaction in children and adolescents with type 1 diabetes in Italy who used different treatment modalities for diabetes care in a real-life context. Methods: In this multicenter, nationwide, cross-sectional study, 1464 participants were enrolled at a routine visit. The following treatment modalities were considered MDI + SMBG; MDI + CGM; Sensor Augmented Pump Therapy; predictive management of low glucose; Hybrid Closed Loop (HCL); Advanced Hybrid Closed Loop (AHCL). Health related quality of life was evaluated by the Italian version of the Diabetes Impact and Device Satisfaction Scale (DIDS) questionnaire. Results: Patients treated with AID systems were more likely to have HbA1c ≤ 6.5 %, higher percentage of time with glucose levels between 70 and 180 mg/dL, lower percentage of time with glucose levels above 180 mg/dL, higher device satisfaction, and reduced impact of diabetes. All the therapeutic modalities with respect to MDI + CGM, except for MDI + SMBG, contributed to increase the device satisfaction. HCL and AHCL respect to MDI + CGM were associated with lower diabetes impact. Conclusion: Real-life use of automated insulin delivery systems is associated with reduced type 1 diabetes impact, increased device satisfaction, and achievement of glycemic goals.

2024 - Implementing Control-IQ technology after a virtual educational camp in children and adolescents with type 1 diabetes: Does time in range plateau over 1 year? [Articolo su rivista]
Scaramuzza, A; Marigliano, M; Bonfanti, R; Cherubini, V; Schiaffini, R; Toni, S; Rabbone, I; The vEC Study, Group; Abate Daga, F; Bassi, M; Berioli, Mg; Bruzzi, P; Calandretti, M; Carducci, C; Cavalli, C; Delvecchio, M; Gesuita, R; Giorda, S; Iafusco, D; Lenzi, L; Lombardo, F; Lo Presti, D; Maffeis, C; Maltoni, G; Mameli, C; Marino, M; Piccini, B; Minuto, N; Mozzillo, E; Piccinno, E; Pignatiello, C; Predieri, B; Redaelli, Fc; Ricciardi, Mr; Rigamonti, A; Ripoli, C; Rosanio, Fm; Salzano, G; Savastio, S; Tiberi, V; Tinti, D; Trada, M; Zanetta, S; Zanfardino, A; Zucchini, S.
abstract

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 - 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 - 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 - Editorial: Debates in clinical management in pediatric endocrinology, volume II [Articolo su rivista]
De Filippo, Gianpaolo; Predieri, Barbara; Delvecchio, Maurizio
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 - 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 - Skeptical Look at the Clinical Implication of Metabolic Syndrome in Childhood Obesity [Articolo su rivista]
Wasniewska, M.; Pepe, G.; Aversa, T.; Bellone, S.; de Sanctis, L.; Di Bonito, P.; Faienza, M. F.; Improda, N.; Licenziati, M. R.; Maffeis, C.; Maguolo, A.; Patti, G.; Predieri, B.; Salerno, M.; Stagi, S.; Street, M. E.; Valerio, G.; Corica, D.; Calcaterra, V.
abstract

Metabolic syndrome (MetS) is defined by a cluster of several cardio-metabolic risk factors, specifically visceral obesity, hypertension, dyslipidemia, and impaired glucose metabolism, which together increase risks of developing future cardiovascular disease (CVD) and type 2 diabetes mellitus (T2D). This article is a narrative review of the literature and a summary of the main observations, conclusions, and perspectives raised in the literature and the study projects of the Working Group of Childhood Obesity (WGChO) of the Italian Society of Paediatric Endocrinology and Diabetology (ISPED) on MetS in childhood obesity. Although there is an agreement on the distinctive features of MetS, no international diagnostic criteria in a pediatric population exist. Moreover, to date, the prevalence of MetS in childhood is not certain and thus the true value of diagnosis of MetS in youth as well as its clinical implications, is unclear. The aim of this narrative review is to summarize the pathogenesis and current role of MetS in children and adolescents with particular reference to applicability in clinical practice in childhood obesity.

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 real-life management of glucose homeostasis abnormalities in pediatric onco-hematological diseases: data from a national survey [Articolo su rivista]
Zanfardino, A.; Bruzzi, P.; Trada, M.; Rapini, N.; Laudani, E.; Tornese, G.; Ortolani, F.; Piccolo, G.; Matonti, L.; Saltarelli, M. A.; Timpanaro, T.; D’Annunzio, G.; Predieri, B.; Rossi, F.; Mura, R.; Barat, V.; Prete, A.; Schiaffini, R.; Zucchini, S.
abstract

: Glycemic abnormalities are a frequent finding in pediatric oncological patients, both during treatment and after its discontinuation. Moreover, impaired glucose tolerance (IGT), impaired fasting glycemia (IFG) and diabetes mellitus (DM) are not rarely diagnosed in non-oncological hematological diseases. To explore the current pediatric Italian approach to the diagnosis and the management of the glycemic alterations in this clinical setting and, thus, to identify and enforce current clinical needs, we submitted an online 23-items survey to all the Italian Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) centers, and surveys were descriptively analyzed. Thirty-nine AIEOP centers were involved in the study. In 2021, among 75278 children and adolescents affected by an oncological or a hematological disease, 1.2 and 0.65% developed DM, while IGT or IFG were widespread in 2.3 and 2.8%, respectively. The main causes of DM were the use of corticosteroids in patients with cancer and the iron overload in patients with thalassemia. Venous fasting plasma glycemia was the most used tool to detect glycemic abnormalities. The performance of oral glucose tolerance test (OGTT) was extremely limited, except when IFG occurred. Despite the diagnosis of DM, ∼45% of patients with cancer and 30% of patients with one hematological disease did not receive an appropriate treatment. In the other cases, insulin was the drug of first choice. Emerging technologies for diabetes care (glucose sensors and insulin pumps) are not largely used yet. The results of our study support the standardization of the care of the glycemic abnormalities during or after onco-hematologic diseases in the pediatric age. Despite the scarce data in pediatric literature, proper guidelines are needed.

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 - A nationwide survey of Italian pediatric diabetologists about COVID-19 vaccination in children and adolescents with type 1 diabetes [Articolo su rivista]
Scaramuzza Andrea, E; Valentino, Cherubini; Riccardo, Schiaffini; Ivana, Rabbone; Diabetes Study Group of the Italian Society for Pediatric Endocrinology and Diabetes, The; Gallo, Francesco; Fichera, Graziella; Arnaldi, Claudia; Bonfanti, Riccardo; Lombardo, Fortunato; De Marco, Rosaria; Pascarella, Filomena; Tornese, Gianluca; Bobbio, Adriana; Suprani, Tosca; Minuto, Nicola; Franceschi, Roberto; Piccinno, Elvira; Mozzillo, Enza; Savastio, Silvia; Piccini, Barbara; Paola Frongia, Anna; Mameli, Chiara; Musolino, Gianluca; Toni, Sonia; Randazzo, Emioli; Frontino, Giulio; Delvecchio, Maurizio; Sogno Valin, Paola; Reinstadler, Petra; Calcaterra, Valeria; De Sanctis, Luisa; Trada, Michela; Susanna Coccioli, Maria; Paola Guerraggio, Lucia; Citriniti, Felice; Lasagni, Anna; Rutigliano, Irene; Andreina Stamati, Filomena; De Berardinis, Fiorella; Zampolli, Maria; Maltoni, Giulio; Fornari, Elena; Ripoli, Carlo; Gaiero, Alberto; Sordelli, Silvia; D’Annunzio, Giuseppe; Predieri, Barbara; Cardinale, Giuliana; Cardella, Francesca; Iafusco, Dario; Corò, Anna; Zucchini, Stefano; Maffeis, Claudio; Giani, Elisa; Tinti, Davide; Cavalli, Claudio
abstract

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 - 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 - COVID-19 forced restrictions did not affect metabolic control in youth with T2D in Italy [Articolo su rivista]
Zucchini, Stefano; Iafusco, Dario; Cherubini, Valentino; De Sanctis, Luisa; Maltoni, Giulio; Lenzi, Lorenzo; Mozzillo, Enza; Calcaterra, Valeria; Gallo, Francesco; Arnaldi, Claudia; Delvecchio, Maurizio; Rabbone, Ivana; Minuto, Nicola; Predieri, Barbara; Zanfardino, Angela; Piscopo, Alessia; Tiberi, Valentina; Tinti, Davide; Rapini, Novella; Toni, Sonia; Schiaffini, Riccardo
abstract

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 - Comment on "Real-World Use of a New Hybrid Closed Loop Improves Glycemic Control in Youth with Type 1 Diabetes" by Messer et al [Articolo su rivista]
Andrea Enzo, Scaramuzza; Riccardo, Bonfanti; Valentino, Cherubini; Marco, Marigliano; Riccardo, Schiaffini; Sonia, Toni; Ivana, Rabbone; Study Group collaborators: Federico Abate Daga, Vec; Bassi, Marta; Giulia Berioli, Maria; Bruzzi, Patrizia; Calandretti, Michela; Carducci, Chiara; Cavalli, Claudio; Delvecchio, Maurizio; Gesuita, Rosaria; Giorda, Sara; Iafusco, Dario; Lenzi, Lorenzo; Lombardo, Fortunato; Lo Presti, Donatella; Maffeis, Claudio; Maltoni, Giulio; Mameli, Chiara; Marino, Monica; Piccini, Barbara; Minuto, Nicola; Mozzillo, Enza; Piccinno, Elvira; Pignatiello, Ciro; Predieri, Barbara; Chiara Redaelli, Francesca; Rossella Ricciardi, Maria; Rigamonti, Andrea; Ripoli, Carlo; Maria Rosanio, Francesco; Salzano, Giuseppina; Savastio, Silvia; Tiberi, Valentina; Tinti, Davide; Trada, Michela; Zanetta, Sara; Zanfardino, Angela; Zucchini), Stefano
abstract

2022 - Corrigendum: The silent epidemic of diabetic ketoacidosis at diagnosis of type 1 diabetes in children and adolescents in italy during the covid-19 pandemic in 2020(Front. Endocrinol., (2022), 13, (878634), 10.3389/fendo.2022.878634) [Articolo su rivista]
Cherubini, V.; Marino, M.; Scaramuzza, A. E.; Tiberi, V.; Bobbio, A.; Delvecchio, M.; Piccinno, E.; Ortolani, F.; Innaurato, S.; Felappi, B.; Gallo, F.; Ripoli, C.; Ricciardi, M. R.; Pascarella, F.; Stamati, F. A.; Citriniti, F.; Arnaldi, C.; Monti, S.; Graziani, V.; De Berardinis, F.; Giannini, C.; Chiarelli, F.; Zampolli, M.; De Marco, R.; Bracciolini, G. P.; Grosso, C.; De Donno, V.; Piccini, B.; Toni, S.; Coccioli, S.; Cardinale, G.; Bassi, M.; Minuto, N.; D'Annunzio, G.; Maffeis, C.; Marigliano, M.; Zanfardino, A.; Iafusco, D.; Rollato, A. S.; Piscopo, A.; Curto, S.; Lombardo, F.; Bombaci, B.; Sordelli, S.; Mameli, C.; Macedoni, M.; Rigamonti, A.; Bonfanti, R.; Frontino, G.; Predieri, B.; Bruzzi, P.; Mozzillo, E.; Rosanio, F.; Franzese, A.; Piredda, G.; Cardella, F.; Iovane, B.; Calcaterra, V.; Berioli, M. G.; Lasagni, A.; Pampanini, V.; Patera, P. I.; Schiaffini, R.; Rutigliano, I.; Meloni, G.; De Sanctis, L.; Tinti, D.; Trada, M.; Guerraggio, L. P.; Franceschi, R.; Cauvin, V.; Tornese, G.; Franco, F.; Musolino, G.; Maltoni, G.; Talarico, V.; Iannilli, A.; Lenzi, L.; Matteoli, M. C.; Pozzi, E.; Moretti, C.; Zucchini, S.; Rabbone, I.; Gesuita, R.
abstract

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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 - 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 - 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 - 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 - 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 - Significant and persistent improvements in time in range and positive emotions in children and adolescents with type 1 diabetes using a closed-loop control system after attending a virtual educational camp [Articolo su rivista]
Rabbone, Ivana; Savastio, Silvia; Pigniatiello, Ciro; Carducci, Chiara; Berioli, Maria Giulia; Cherubini, Valentino; Lo Presti, Donatella; Maltoni, Giulio; Mameli, Chiara; Marigliano, Marco; Minuto, Nicola; Mozzillo, Enza; Piccinno, Elvira; Predieri, Barbara; Rigamonti, Andrea; Ripoli, Carlo; Schiaffini, Riccardo; Lombardo, Fortunato; Tinti, Davide; Toni, Sonia; Zanfardino, Angela; Scaramuzza, Andrea Enzo
abstract

Objective To evaluate the six-month impact of the advanced automated functions of a closed-loop control (CLC) system (Control-IQ) and a virtual educational camp (vEC) on emotions and time in range (TIR) of children and adolescents with type 1 diabetes. Methods Children and their parents participated in a three-day vEC. Clinical, glucose, and emotion data were evaluated before, just after, and six months after the vEC. Emotions were evaluated using adapted Plutchik's and Geneva Emotion Wheels. Results Forty-three children and adolescents (7-16 years) showed significant improvements in positive emotions immediately and six months after the vEC (67% and 65% vs 38%, p < 0.05, respectively), while mixed emotions were reduced (32% and 15% vs 61%, p < 0.05 and p < 0.001, respectively). The median percentage TIR increased from 64% (IQR 54-72) to 75% (IQR 70-82) with Control-IQ (p < 0.001) six months after the vEC. Conclusions Positive emotions (joy, serenity, and satisfaction) significantly improved while mixed emotions were significantly worse six months after the initiation of a CLC system (Control-IQ) and a vEC.

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 - The Silent Epidemic of Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes in Children and Adolescents in Italy During the COVID-19 Pandemic in 2020 [Articolo su rivista]
Cherubini, Valentino; Marino, Monica; Scaramuzza, Andrea E; Tiberi, Valentina; Bobbio, Adriana; Delvecchio, Maurizio; Piccinno, Elvira; Ortolani, Federica; Innaurato, Stefania; Felappi, Barbara; Gallo, Francesco; Ripoli, Carlo; Ricciardi, Maria Rossella; Pascarella, Filomena; Stamati, Filomena A; Citriniti, Felice; Arnaldi, Claudia; Monti, Sara; Graziani, Vanna; De Berardinis, Fiorella; Giannini, Cosimo; Chiarelli, Francesco; Zampolli, Maria; De Marco, Rosaria; Bracciolini, Giulia Patrizia; Grosso, Caterina; De Donno, Valeria; Piccini, Barbara; Toni, Sonia; Coccioli, Susanna; Cardinale, Giuliana; Bassi, Marta; Minuto, Nicola; D'Annunzio, Giuseppe; Maffeis, Claudio; Marigliano, Marco; Zanfardino, Angela; Iafusco, Dario; Rollato, Assunta S; Piscopo, Alessia; Curto, Stefano; Lombardo, Fortunato; Bombaci, Bruno; Sordelli, Silvia; Mameli, Chiara; Macedoni, Maddalena; Rigamonti, Andrea; Bonfanti, Riccardo; Frontino, Giulio; Predieri, Barbara; Bruzzi, Patrizia; Mozzillo, Enza; Rosanio, Francesco; Franzese, Adriana; Piredda, Gavina; Cardella, Francesca; Iovane, Brunella; Calcaterra, Valeria; Berioli, Maria Giulia; Lasagni, Anna; Pampanini, Valentina; Patera, Patrizia Ippolita; Schiaffini, Riccardo; Rutigliano, Irene; Meloni, Gianfranco; De Sanctis, Luisa; Tinti, Davide; Trada, Michela; Guerraggio, Lucia Paola; Franceschi, Roberto; Cauvin, Vittoria; Tornese, Gianluca; Franco, Francesca; Musolino, Gianluca; Maltoni, Giulio; Talarico, Valentina; Iannilli, Antonio; Lenzi, Lorenzo; Matteoli, Maria Cristina; Pozzi, Erica; Moretti, Carlo; Zucchini, Stefano; Rabbone, Ivana; Gesuita, Rosaria
abstract

To compare the frequency of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes in Italy during the COVID-19 pandemic in 2020 with the frequency of DKA during 2017-2019.

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 - Time With Glucose Level in Target Range Among Children and Adolescents With Type 1 Diabetes After a Software Update to a Closed-Loop Glucose Control System [Articolo su rivista]
Marigliano, Marco; Scaramuzza, Andrea E; Bonfanti, Riccardo; Rabbone, Ivana; Schiaffini, Riccardo; Toni, Sonia; Cherubini, Valentino; for the Virtual Educational Camp (vEC) Study, Group; Predieri, Barbara; Bruzzi, Patrizia
abstract

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 - Alti livelli di anticorpi antitransglutaminasi predicono la malattia celiaca in bambini e adolescenti italiani con diabete mellito tipo 1. [Abstract in Atti di Convegno]
Mozzillo, Enza; Di Candia, Francesca; Maria Rosanio, Francesco; Cardella, Francesca; Cherubini, Valentino; Susanna Coccioli, Maria; D'Annunzio, Giuseppe; De Bernardis, Fiorella; Delvecchio, Maurizio; Felappi, Barbara; Franceschi, Roberto; Gallo, Francesco; Grosso, Caterina; Iafusco, Dario; Inzaghi, Elena; Maffeis, Claudio; Maltoni, Giulio; Passanisi, Stefano; Piccini, Barbara; Piccinno, Elvira; Predieri, Barbara; Rossella Ricciardi, Maria; Roppolo, Rosalia; Savastio, Silvia; Tornese, Gianluca; Auricchio, Renata; Franzese, Adriana
abstract

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 - 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 - Controllo metabolico e parametri di rischio cardiovascolare negli adolescenti con dm2 nell’anno della pandemia: studio multicentrico [Abstract in Atti di Convegno]
Zucchini, Stefano; Iafusco, Dario; Cherubini, Valentino; Schiani, Riccardo; Lenzi, Lorenzo; Mozzillo, Enza; Calcaterra, Valeria; Gallo, Francesco; Arnaldi, Claudia; Delvecchio, Maurizio; Rabbone, Ivana; Minuto, Nicola; Zanfardino, Angela; Piscopo, Alessia; Tiberi, Valentina; Rapini, Novella; Toni, Sonia; Maltoni, Giulio; Predieri, Barbara
abstract

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 - Diabetes and Prediabetes in Children With Cystic Fibrosis: A Systematic Review of the Literature and Recommendations of the Italian Society for Pediatric Endocrinology and Diabetes (ISPED) [Articolo su rivista]
Mozzillo, E; Franceschi, R; Piona, C; Passanisi, S; Casertano, A; Pjetraj, D; Maltoni, G; Calcaterra, V; Cauvin, V; Cherubini, V; D’Annunzio, G; Franzese, A; Frongia, Ap; Lombardo, F; Lo Presti, D; Matteoli, Mc; Piccinno, E; Predieri, B; Rabbone, I; Scaramuzza, Ae; Toni, S; Zucchini, S; Maffeis, C; Schiaffini, R on behalf of the Diabetes Study Group of the Italian Society for Pediatric Endocrinology and Diabetology (ISPED)
abstract

Cystic fibrosis related diabetes (CFRD) is a comorbidity of cystic fibrosis (CF) that negatively impacts on its clinical course. Prediabetes is an important predictor of either CFRD development and unfavorable prognosis of CF in both pediatric and adult patients. International guidelines recommend insulin only in case of CFRD diagnosis. Whether early detection and treatment of prediabetes may contribute to improve the clinical course of CF is still debated. A subgroup of pediatric diabetologists of the Italian Society for Pediatric Endocrinology and Diabetology (ISPED) performed a systematic review of the literature based on predefined outcomes: impact of pre-diabetes on clinical outcomes and on the risk of developing CFRD; diagnosis of diabetes and pre-diabetes under 10 years of age; effectiveness of therapy on glycemic control, impact of therapy on pulmonary function and nutritional status. Thirty-one papers were selected for the analysis data presented in these papers were reported in tables sorted by outcomes, including comprehensive evidence grading according to the GRADE approach. Following the grading of the quality of the evidence, the entire ISPED diabetes study group achieved consensus for the Italian recommendations based on both evidence and clinical experience. We concluded that in patients with CF, prediabetes should be carefully considered as it can evolve into CFRD. In patients with CF and prediabetic conditions, after complete evaluation of the OGTT trend, glucometrics, glycemic values measured during pulmonary exacerbations and/or steroid therapy, early initiation of insulin therapy could have beneficial effects on clinical outcomes of patients with CF and prediabetes.

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 - Editorial: Debates in Clinical Management in Pediatric Endocrinology [Articolo su rivista]
Marcovecchio, Maria Loredana; Predieri, Barbara; De Filippo, Gianpaolo; Delvecchio, Maurizio
abstract

2021 - Effectiveness of a closed-loop control system and a virtual educational camp for children and adolescents with type 1 diabetes: a prospective multicenter real-life study [Articolo su rivista]
Cherubini, Valentino; Rabbone, Ivana; Berioli, Maria Giulia; Giorda, Sara; Lo Presti, Donatella; Maltoni, Giulio; Mameli, Chiara; Marigliano, Marco; Marino, Monica; Minuto, Nicola; Mozzillo, Enza; Piccinno, Elvira; Predieri, Barbara; Ripoli, Carlo; Schiaffini, Riccardo; Rigamonti, Andrea; Salzano, Giuseppina; Tinti, Davide; Toni, Sonia; Zanfardino, Angela; Scaramuzza, Andrea Enzo; Gesuita, Rosaria; vEC Study Group (Tiberi, Valentina; Savastio, Silvia; Pigniatiello, Ciro; Trada, Michela; Zucchini, Stefano; Redaelli, Francesca Chiara; Maffeis, Claudio; Bassi, Marta; Rosanio, Francesco Maria; Delvecchio, Maurizio; Bruzzi, Patrizia; Ricciardi, Maria Rossella; Carducci, Chiara; Bonfanti, Riccardo; Lombardo, Fortunato; Piccini, Barbara; Iafusco, Dario; Calandretti, Michela; Abate Daga, Federico)
abstract

Aim: Education maximizes the benefits of new diabetes technology. Here we evaluated the impact of a virtual educational camp (vEC) on glucose control in children and adolescents with type 1 diabetes using a closed-loop control (CLC) system. Materials and methods: This was a prospective multicenter study of children and adolescents with type 1 diabetes using the Tandem Basal-IQ™ system. Insulin pumps were upgraded to Control-IQ™, and children and their parents participated in a three-day multidisciplinary vEC. Clinical data, glucose metrics, and HbA1c were evaluated over the 12 weeks prior to the Control-IQ update and over the 12 weeks after the vEC. Results: Forty-three children and adolescents (aged 7-16 years) with type 1 diabetes and their families participated in the vEC. The median percentage of time in target range (70-180 mg/dL; TIR) increased from 64% (interquartile range [IQR] 56-73) with Basal-IQ to 76% (IQR 71-81) with Control-IQ (p < 0.001). After the vEC, over 75% of participants achieved TIR >70%. The percentage of time between 180-250 mg/dL and above 250 mg/dL decreased by 5% (p < 0.01) and 6% (p < 0.01), respectively, while the time between 70-54 mg/dL and below 54 mg/dL remained low and unaltered. HbA1c decreased by 0.5% (p < 0.01). There were no diabetic ketoacidosis or severe hypoglycemia episodes. Conclusions: In this study of children managing their diabetes in the real-world setting, over 75% of children who participated in a vEC after starting a CLC system could obtain and maintain a TIR >70%. The vEC was feasible and resulted in a significant and persistent improvement in TIR in children and adolescents with type 1 diabetes.

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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - Metabolic control and cardiovascular (CV) risk factors in adolescents with T2DM in the pandemic year: a multicentre study [Abstract in Rivista]
Zucchini, S.; Iafusco, D.; Cherubini, V.; Schiaffini, R.; Lenzi, L.; Mozzillo, E.; Calcaterra, V.; Gallo, F.; Arnaldi, C.; Delvecchio, M.; Rabbone, I.; Minuto, N.; Predieri, B.; Zanfardino, A.; Piscopo, A.; Tiberi, V.; Rapini, N.; Toni, S.; Maltoni, G.
abstract

Introduction: Lockdown due to pandemic has caused an increase in BMI and CV risk factors in obese patients (pts), while pts with T1DM showed greater glucose stability with unchanged HbA1c levels. Obese adolescents with T2DM may have been negatively affected by social restrictions. Objectives: Primary aim of the study was to compare HbA1c levels between pre-lockdown and first 4 months of 2021 of adolescents with T2DM. Secondary aims were to compare BMI, total and HDL cholesterol, triglycerides between the 2 periods. Methods: We collected data of 56 pts (23 M, 33 F) from 12 Italian centres of the Italian Society for Pediatric Endocrinology and Diabetology (ISPED). Inclusion criteria were age 10-20 years, T2DM, visit 1 in the 4 months before lock-down and same parameters at visit 2 in the first 4 months of 2021. Age at diagnosis was 13.1±2.7 yrs and 14.7±2.4 yrs at visit 1, family history for T2DM in one or both parents in 57% of cases. Results: HbA1c levels showed a non significant increase between visit 1 and 2 (7.1±1.8 vs 7.3±2.1%; p=NS). In 22 pts HbA1c increased by more than 0.5%, in 12 decreased (<0.5%). 20 pts showed a HbA1c>7% at visit 1 and 24 at visit 2. There were no significant changes between the 2 visits as for BMI (31.2±5.9 vs 31±6.2), total cholesterol (176±35 vs 178±31 mg/dl), HDL cholesterol (43.6±9 vs 45.5±12 mg/dl), triglycerides (143±198 vs 130±73 mg/dl). There were no differences between the 2 sexes. HbA1c at visit 1 was positively correlated with that of visit 2 only in females (p=0.0001). Treatment at visit 1 was none in 4 pts, metformin in 27 pts, insulin in 8 pts and metformin+insulin in 17 pts. Pts on insulin were 25 at visit 1 and 22 at visit 2. Conclusions: The long period of social restrictions does not seem to have affected metabolic control and CV risk factors in our adolescents with T2DM followed in the Italian centres of the ISPED. Metabolic control was apparently more irregular in male patients compared to that of female patients.

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 - 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 - Poor health related quality of life and unhealthy lifestyle habits in weight-loss treatment-seeking youth [Articolo su rivista]
Mozzillo, E.; Zito, E.; Calcaterra, V.; Corciulo, N.; Di Pietro, M.; Di Sessa, A.; Franceschi, R.; Licenziati, M. R.; Maltoni, G.; Morino, G.; Predieri, B.; Street, M. E.; Trifiro, G.; Galle, F.; Franzese, A.; Valerio, G.
abstract

Obesity is associated with unhealthy lifestyle behaviors and poor Health Related Quality of Life (HRQOL). The cumulative effect of lifestyle behaviors on HRQOL has been demonstrated in chronically ill adolescents, but not in adolescents with obesity. The present study aimed to assess the association between HRQOL and adherence to the Mediterranean Diet (MD) and/or low levels of physical activity (PA) in a large sample of outpatient adolescents with overweight or obesity seeking weight loss treatment. Four-hundred-twenty participants were enrolled from 10 Italian outpatient clinics. The demographics and anthropometric features, KIDMED scores, and exercise levels of the participants were collected, together with parental features. The HRQOL was assessed by the Pediatric Quality of Life Inventory (PedsQL™), Adolescents Version 4.0. PedsQL total score and functioning subscales were lower in adolescents who reported one or two unhealthy habits. Compared with the high/intermediate groups, the risk of low HRQOL was twice as high for each unit increase in BMI SDS, while the percentage was reduced by 12.2% for every unit increase in the KIDMED score and by 32.3% for each hour increase of exercise. The clustering of these two unhealthy behaviors conferred a 120% higher risk of low HRQOL. Similarly, adolescents displaying better diet quality and/or a physically more active lifestyle have better physical and psychological functioning. Further studies are needed to disclose whether these characteristics may be predictive of better adherence to weight loss treatment.

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 - 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 - 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 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 - 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 - 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 - Cardiovascular risk factors in children and adolescents with type 1 diabetes in Italy: a multicentric observational study [Articolo su rivista]
Fornari, E.; Piona, C.; Rabbone, I.; Cardella, F.; Mozzillo, E.; Predieri, B.; Lo Presti, D.; Cherubini, V.; Patera, I. P.; Suprani, T.; Bonfanti, R.; Cauvin, V.; Lombardo, F.; Zucchini, S.; Zanfardino, A.; Giani, E.; Reinstadler, P.; Minuto, N.; Buganza, R.; Roppolo, R.; Marigliano, M.; Maffeis, C.
abstract

Aims: To assess the prevalence of cardiovascular risk factors (CVRFs) and to identify the variables associated with CVRFs in a cohort of children and adolescents with Type 1 Diabetes. Methods: 2021 subjects, 2-18 year-old, were recruited in 17 Italian Pediatric Diabetes Centers. Anthropometric, blood pressure, biochemical (HbA1c, lipid profile, ACR), insulin therapy, physical activity level, smoking and family socio-economic status data were collected. CVRFs prevalence and their distribution were analyzed according to age and binary logistic regression was performed with positivity for at least one major CVRF (BMI-SDS > +2SD, blood pressure > 90th percentile, LDL cholesterol>100 mg/dL) as dependent variable and age, duration of illness, gender, HbA1c and physical activity, as independent variables. Results: The prevalence of CVFRs not at the recommended target was respectively: 32.5% one CVRF, 6.7% two CVRFs and 0.6% three CVRFs, with no significant differences across the 3 age groups (2-10, 10-15, 15-18 years). In the total sample, HbA1c and inadequate physical activity were associated with a higher probability of having at least one major CVRF. This probability was associated with physical activity in the 2-10-year-old group, with physical activity and HbA1c in the 10-15-year-old group and with HbA1c only in subjects older than 15 years. Conclusions: More than 30% of subjects had at least a major CVRF. Early detection of CVRFs may be useful to enforce the therapeutic intervention in this subgroup, in order to reduce the risk to develop cardiovascular complications.

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 - 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 - Has COVID-19 Delayed the Diagnosis and Worsened the Presentation of Type 1 Diabetes in Children? [Articolo su rivista]
Ivana, Rabbone; Riccardo, Schiaffini; Valentino, Cherubini; Claudio, Maffeis; Andrea, Scaramuzza; Study Group of the Italian Society for Pediatric Endocrinology and Diabetes (Enrica Bertelli, Diabetes; Ferlito, Lucia; Bobbio, Adriana; Schieven, Eleonardo; Delvecchio, Maurizio; Maltoni, Giulio; Reinstadler, Petra; Felappi, Barbara; Gallo, Francesco; Ripoli, Carlo; Pascarella, Filomena; A Stamati, Filomena; Lo Presti, Donatella; Citriniti, Felice; Tumini, Stefano; Zampolli, Maria; De Marco, Rosaria; Cavalli, Claudio; De Donno, Valeria; Toni, Sonia; Susanna Coccioli, Maria; d'Annunzio, Giuseppe; Sogno Valin, Paola; Cirillo, Dante; Sordelli, Silvia; Lombardo, Fortunato; Bonfanti, Riccardo; Mameli, Chiara; Predieri, Barbara; Franzese, Adriana; Iafusco, Dario; Savastio, Silvia; Piredda, Gavina; Cardella, Francesca; Calcaterra, Valeria; Randazzo, Emioli; Favia, Anna; Suprani, Tosca; Lasagni, Alessandra; Rapini, Novella; Rutigliano, Irene; Gaiero, Alberto; De Sanctis, Luisa; Cauvin, Vittoria; Minute, Marta; Tornese, Gianluca; Franco, Francesca; Musolino, Gianluca; Marigliano, Marco; Innaturato, Silvia; Arnaldi), Claudia
abstract

Objective: To evaluate whether the diagnosis of pediatric type 1 diabetes or its acute complications changed during the early phase of the coronavirus disease 2019 (COVID-19) pandemic in Italy. Research design and methods: This was a cross-sectional, Web-based survey of all Italian pediatric diabetes centers to collect diabetes, diabetic ketoacidosis (DKA), and COVID-19 data in patients presenting with new-onset or established type 1 diabetes between 20 February and 14 April in 2019 and 2020. Results: Fifty-three of 68 centers (77.9%) responded. There was a 23% reduction in new diabetes cases in 2020 compared with 2019. Among those newly diagnosed patient who presented in a state of DKA, the proportion with severe DKA was 44.3% in 2020 vs. 36.1% in 2019 (P = 0.03). There were no differences in acute complications. Eight patients with asymptomatic or mild COVID-19 had laboratory-confirmed severe acute respiratory syndrome coronavirus 2. Conclusions: The COVID-19 pandemic might have altered diabetes presentation and DKA severity. Preparing for any "second wave" requires strategies to educate and reassure parents about timely emergency department attendance for non-COVID-19 symptoms.

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 - 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 - Socioeconomic Inequalities Increase the Probability of Ketoacidosis at Diagnosis of Type 1 Diabetes: A 2014–2016 Nationwide Study of 2,679 Italian Children [Articolo su rivista]
Gesuita, R.; Maffeis, C.; Bonfanti, R.; Cardella, F.; Citriniti, F.; D'Annunzio, G.; Franzese, A.; Iafusco, D.; Iannilli, A.; Lombardo, F.; Maltoni, G.; Patera, I. P.; Piccinno, E.; Predieri, B.; Rabbone, I.; Ripoli, C.; Toni, S.; Schiaffini, R.; Bowers, R.; Cherubini, V.
abstract

This study aims to compare the frequency of Diabetic Ketoacidosis (DKA) at diagnosis in 2014–2016 with the one previously reported in 2004–2013; and to assess the association between family socioeconomic status and DKA at type 1 diabetes (T1D) diagnosis in children <15 years of age from 2014 to 2016. Methods: This nationwide, population-based, observational study included 2,679 children diagnosed with T1D from 54 Italian centers for pediatric diabetes during 2014–2016. The ISPAD criteria for DKA were used as a standard reference. The overall and by age frequency of DKA between the two time periods were compared. The association between family socioeconomic status and DKA was assessed using multiple logistic regression analysis. Results: Nine hundred and eighty nine children had DKA (36.9, 95% CI: 35.1–38.8). The frequency of DKA was significantly lower in 2014–2016 in comparison to 2004–2013 (40.3, 95% CI: 39.3–41.4, p = 0.002). The probability of having DKA at diagnosis was lower in mothers with a high level of education (OR = 0.69, 95% CI: 0.51–0.93) or a high level of occupation (OR = 0.76, 95% CI: 0.58 0.99), and in fathers with a high level of occupation (OR = 0.72, 95% CI: 0.55–0.94). Children living in Southern Italy had a higher probability of diagnosis with severe DKA than children living in Central Italy. Conclusion: There was a decrease in the frequency of DKA in children diagnosed with T1D under 15 years of age during 2014–2016. However, DKA frequency remains unacceptably high. This study demonstrated that socioeconomic inequalities, measured as low education and occupational levels, were associated with an increased probability of DKA at T1D diagnosis.

2019 - Dolore addominale in un’adolescente: e se fosse un problema di ormoni? [Articolo su rivista]
Ciancia, Silvia; Predieri, Barbara; Iughetti, Lorenzo
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 - 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 - 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 - 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 - 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 - Safety outcomes during pediatric GH therapy: final results from the prospective GeNeSIS observational program [Articolo su rivista]
Child, Cj; Zimmermann, Ag; Chrousos, Gp; Cummings, E; Deal, Cl; Hasegawa, T; Jia, N; Lawrence, S; Linglart, A; Loche, S; Maghnie, M; Pérez Sánchez, J; Polak, M; Predieri, B; Richter-Unruh, A; Rosenfeld, Rg; Yeste, D; Yorifuji, T; Blum, Wf
abstract

CONTEXT: Safety concerns regarding premature mortality, diabetes, neoplasia and cerebrovascular disease in association with growth hormone (GH) therapy have been raised. OBJECTIVE: To assess incidence of key safety outcomes. DESIGN: Prospective, multinational, observational study (1999-2015). SETTING: 22,311 GH-treated children from 827 investigative sites in 30 countries. PATIENTS: Children with growth disorders. INTERVENTIONS: GH treatment. MAIN OUTCOME MEASURES: Standardized mortality (SMR) and incidence (SIR) ratios with 95% confidence intervals (CI) for mortality, diabetes, and primary cancer, using general population registries. RESULTS: Predominant short stature diagnoses were GH deficiency (63%), idiopathic short stature (13%), and Turner syndrome (8%), with mean±SD follow-up of 4.2±3.2 years (∼92,000 person-years [PY]). Forty-two deaths occurred in patients with follow-up, with SMR (95% CI) of 0.61 (0.44-0.82); the SMR was elevated for patients with cancer-related organic GH deficiency (5.87 [3.21-9.85]). Based on 18 cases, Type 2 diabetes (T2DM) risk was elevated (SIR 3.77 [2.24-5.96]), but 72% had risk factors. In patients without cancer history, 14 primary cancers were observed (SIR 0.71 [0.39-1.20]). Second neoplasms occurred in 31/622 (5.0%) cancer survivors (10.7 [7.5-15.2] cases/1000 PY), and intracranial tumor recurrences in 67/823 (8.1%) tumor survivors (16.9 [13.3-21.5] cases/1000 PY). All 3 hemorrhagic stroke cases had risk factors. CONCLUSIONS: GeNeSIS data support the favourable safety profile of pediatric GH treatment. Overall risk for death or primary cancer was not elevated in GH-treated children, and no hemorrhagic strokes occurred in patients without risk factors. T2DM incidence was elevated compared to the general population, but most cases had diabetes risk factors.

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 - 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 - 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 - 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 - 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 Bone Mineral Density in a Cohort of Children with Growth Hormone Deficiency [Abstract in Rivista]
Cenciarelli, Valentina; Bruzzi, Patrizia; Predieri, Barbara; Caterina, Cerbone; Madeo, Simona Filomena; Leo, Francesco
abstract

Background: Growth Hormone (GH) plays an important role in linear growth and in bone turnover during childhood. GH deficiency (GHD) may cause secondary osteoporosis associated to low bone mineral density (BMD), impairment of bone turnover and increased fracture rate. The effects of treatment with recombinant human Growth Hormone (rhGH) on bone metabolism are controversial. We aimed to assess BMD using dual energy x-ray absorptiometry (DEXA) among a cohort of children with GHD before rhGH therapy. Furthermore, we aimed to evaluate the association between BMD and auxological, biochemical and therapeutic data at baseline and during rhGH therapy. Methods: We enrolled 193 patients (9.68 ± 3.27 years, 58% males, 75% in a pre-pubertal age) with diagnosed GHD. DEXA was performed before treatment. Anamnestic, anthropometric, biochemical and radiological data were evaluated at baseline and during rhGH treatment (6, 12 and 24 months). Results: The median value of BMD Z-score before rhGH therapy was -1.15 ± 0.97. Analyzing BMD values at baseline, we found differences between pubertal and pre-pubertal patients (BMD SDS -1.54± 0.95 vs. -0.97±0.93; p < 0.001) and between patients with a normal brain magnetic resonance imaging (MRI) and subjects with a pathologic MRI (BMD SDS -1.09±0.99 vs.-1.48±0.82 p 0.03, respectively). The absolute value of BMD (g/cm²) was positively correlated with height SDS (r 0.20, p <0.05), BMI SDS (r 0.24, p <0.05) and IGF-1 values (r 0.33, p <0.05); BMD SDS value was positively correlated with target height SDS (r 0.28, p <0.05) and BMI SDS (r 0.36, p <0.05) whereas there was a negative correlation between BMD SDS and the age at GHD diagnosis (r² 0.40, p <0.05). There was no association between BMD values and biochemical and therapeutic data. Conclusions: Our study shows that pubertal patients have a lower BMD than pre-pubertal ones as a consequence of the mild bone demineralization (BMD Z-score -1.15±0.97) secondary to GHD. Therefore, our data suggest starting rhGH therapy early as to promote an optimal growth. DEXA might represent a valid mean to complete the diagnosis in GHD patients and to optimally orient the therapeutic decisions; it should be repeated at the end of treatment in order to evaluate its effect on bone metabolism.

2018 - I DISORDINI DELLO SVILUPPO SESSUALE E LE MALFORMAZIONI DELL’APPARATO GENITALE [Capitolo/Saggio]
Lucaccioni, Laura; Predieri, Barbara; Tridenti, Gabriele; Vezzani, Cristina
abstract

La differenziazione sessuale è un processo complesso, che si articola durante tutta l’embriogenesi portando allo sviluppo di differenti tipologie di “sesso”. L’evoluzione naturale del sistema riproduttivo porta di default alla formazione di gonadi e genitali esterni femminili. Perché si compia la differenziazione in senso “maschile” sono necessari vari cofattori quali un gene SRY correttamente funzionante, tessuto gonadico che produca AMH e testosterone, recettori ormonali funzionanti nei tessuti bersaglio. Eventuali alterazioni di questo delicato processo possono portare alla presenza di Disordini dello Sviluppo Sessuale (DSD). Le malformazioni dell’apparato genitale (MAG) sono deviazioni dalla normale anatomia che possono ridurre la capacità riproduttiva di una donna o, in casi complessi (anomalie ostruttive) possono mettere a rischio la sua stessa salute. Embriologicamente derivano da difetti di formazione, canalizzazione, fusione o riassorbimento dei dotti di Muller.

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 - 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 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 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.

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 - 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 - 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 - 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 - DETERMINANTI DELLA HEALTH RELATED QUALITY OF LIFE (HRQOL) IN ADOLESCENTI OBESI ITALIANI [Abstract in Atti di Convegno]
Franzese, Adriana; Zito, Eugenio; Calcaterra, Valeria; Corciulo, Nicola; Di Pietro, Mario; Di Sessa, Anna; Franceschi, Roberto; Rosaria Licenziati, Maria; Maltoni, Giulio; Morino, Giuseppe; Predieri, Barbara; Elizabeth Street, Maria; Trifirò, Giuliana; Mozzillo, Enza; Valerio, Giuliana
abstract

OBIETTIVI Valutare i determinanti socio-economici, legati allo stile di vita e alla gravità dell’eccesso ponderale della qualità di vita collegata alla salute (HRQoL) in un campione ambulatoriale di adolescenti obesi italiani reclutati in uno studio osservazionale multicentrico. METODI 210 adolescenti (109 M; età 14,2±1,1 anni; range 13-16) con obesità primaria (BMI > 95° percentile curve di Cacciari et al.), BMI medio 32,4±5,3; BMI SDS 2,3±0,6; scolarità padre 10,6±3,7 anni; scolarità madre 10,8±3,8 anni, sono stati arruolati consecutivamente alla prima visita in 12 centri italiani per la cura dell’obesità pediatrica afferenti alla SIEDP. Lo stile di vita è stato indagato con questionario su attività fi sica (quanti giorni alla settimana pratichi almeno 60 min in attività fi sica moderata/intensa?), sedentarietà (somma ore giornaliere di TV, videogiochi, computer) e qualità della dieta (indice Kidmed). La HRQoL dell’adolescente era valutata con il PedsQL™ versione 4, modulo 13-18 anni, composto da 4 scale: funzionamento fisico, emozionale, sociale, scolastico, da cui si ottengono un punteggio del funzionamento fisico, un punteggio del funzionamento psicosociale (emozionale, sociale e scolastico), un punteggio generale. RISULTATI Il PedsQL generale era 72,6±14,6, il funzionamento fisico 73,7±17,8 e il funzionamento psicosociale 72,0±15,3, senza differenze di genere. Il punteggio generale correlava negativamente con età e BMI-SDS e positivamente con il livello culturale di entrambi i genitori, ore di attività fi sica e indice Kidmed. L’analisi della regressione multipla indicava che gli unici determinanti indipendenti associati al PedsQL generale erano livelli di AF (beta 3,041, p<0.01), indice Kidmed (beta 2,488, p<0,02) e BMI-SDS (beta -1,94, p=0,05) controllando per età, livello culturale dei genitori, area geografi ca e ore di sedentarietà. Associazioni indipendenti signifi cative sono state riscontrate tra livelli di AF e i domini del funzionamento fisico (beta 3,628, p<0.01) e psicosociale (beta 2,156, p< 0,04). CONCLUSIONI La significativa associazione tra stile di vita più salutare e qualità della vita negli adolescenti obesi suggerisce l’importanza di promuovere l’attività fisica e migliorare la qualità nella dieta non solo per ottenere un calo ponderale, ma anche per migliorare lo stato di benessere generale.

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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - Whole lipid profile and not only HDL cholesterol is impaired in children with coexisting type 1 diabetes and untreated celiac disease [Articolo su rivista]
Salardi, Silvana; Maltoni, Giulio; Zucchini, Stefano; Iafusco, Dario; Zanfardino, Angela; Confetto, Santino; Toni, Sonia; Zioutas, Maximiliano; Marigliano, Marco; Cauvin, Vittoria; Franceschi, Roberto; Rabbone, Ivana; Predieri, Barbara; Schiaffini, Riccardo; Salvatoni, Alessandro
abstract

Aims: Low HDL cholesterol (HDL-C) levels have been described in patients with coexisting type 1 diabetes mellitus (T1DM) and celiac disease (CD). Data on other possible lipid abnormalities that could further increase cardiovascular risk in these patients are scarce and incomplete. Aim of this retrospective multicenter study was to evaluate whole lipid profiles, besides HDL-C, in children with T1DM associated with biopsy-proven CD, and to investigate the influence of age and degree of adherence to gluten-free diet (GFD) on lipid changes.Methods: A total of 261 children with both T1DM and CD were enrolled. Serum lipid profiles at CD diagnosis were compared with those after 1 year of GFD and with those of 224 matched children with T1DM alone. The adherence to GFD was judged by means of CD-related antibodies.Results: At CD diagnosis, children with T1DM + CD showed higher LDL cholesterol (LDL-C) compared to children with T1DM alone. Gluten withdrawal failed to normalize LDL-C levels, not even in completely adherent individuals. HbA1c values were not influenced by GFD. The youngest children were characterized at diagnosis by lower levels of total cholesterol and on treatment by a greater decrease in triglycerides levels. Conclusions: An unfavorable lipid profile, characterized not only by low HDL-C levels but also by high LDL-C values, may increase the risk of cardiovascular disease in children with T1DM and untreated CD. Therefore, a strict gluten-free diet is mandatory in these children, especially the youngest.

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 - A Prospective Evaluation of Urinary Gonadotrophins for Assessment and Management of Pubertal Disorders [Abstract in Rivista]
Lucaccioni, Laura; Mcneilly, Jane; Mcmillan, Martin; Kyriakoua, Andreas; Shaikh, Guftar; Predieri, Barbara; Mason, Avril; Ahmed, Faisal
abstract

UGn is a valuable, non-invasive instrument for diagnosis of early puberty. Its clinical utility in personalising GnRH-a therapy needs further exploration.

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 - Celiac Disease Negatively Influences Lipid Profiles in Youngest Children With Type 1 Diabetes: Effect of the Gluten-Free Diet [Articolo su rivista]
Salardi, Silvana; Maltoni, Giulio; Zucchini, Stefano; Iafusco, Dario; Confetto, Santino; Zanfardino, Angela; Toni, Sonia; Piccini, Barbara; Zioutas, Maximiliano; Marigliano, Marco; Cauvin, Vittoria; Franceschi, Roberto; Rabbone, Ivana; Predieri, Barbara; Schiaffini, Riccardo; Salvatoni, Alessandro; Reinstadler, Petra; Berioli, Giulia; Cherubini, Valentino; D'Annunzio, Giuseppe
abstract

The association between low HDL cholesterol (HDL-C) concentrations and increased cardiovascular risk is well established. Low HDL-C levels were found in subjects with type 1 diabetes (T1D) who presented complications and in untreated subjects with celiac disease (CD). The association between TID and CD might therefore enhance this lipid abnormality and accelerate the atherosclerotic process.

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 - 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 - 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 - 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 - 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 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 - 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 - 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 - 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 - 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 - 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 - 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 - Ruolo delle gonadotropine urinarie nella diagnosi e nel trattamento dei disturbi dello sviluppo puberale [Abstract in Atti di Convegno]
Lucaccioni, Laura; Mcneilly, J.; Mcmillan, M.; Kyriakou, A.; Shaikh, M. G.; Wong, J.; Predieri, Barbara; Mason, A.; Ahmed, S. F.
abstract

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2015 - The Risk of Metabolic Syndrome among Dyslipidemic Children and Adolescents [Abstract in Rivista]
Predieri, Barbara; Colombini, Giulia; Mazzoni, Silvia; Bruzzi, Patrizia; Lucaccioni, Laura
abstract

In our outpatient setting of dyslipidemic children, the finding of high TG and low HDL levels helps in discriminating patients with MetS, especially when associated with increased BMI-SDS, insulin resistance and high SBP. Our data highlight the presence of a cluster of conditions that concurrently increased the cardiovascular risk already in childhood and, therefore, that had to be globally investigated.

2015 - The measurement of urinary gonadotrophins for assessment and management of pubertal disorders [Abstract in Rivista]
Lucaccioni, Laura; Mcneilly, Jane; Mcmillan, Martin; Kyriakou, Andreas; Wong, S C; Predieri, Barbara; Shaikh, M Guftar; Mason, Avril; Ahmed, S Faisal
abstract

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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.

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

N.A.

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 - 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.

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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - Type 1 diabetes and measles, mumps and rubella childhood infections within the Italian Insulin-dependent Diabetes Registry [Articolo su rivista]
Ramondetti, F; Sacco, S; Comelli, M; Bruno, G; Falorni, A; Iannilli, A; D'Annunzio, G; Iafusco, D; Songini, M; Toni, S; Cherubini, V; Carle, F; Cerutti, F; Novelli, G; Bianchi, L; Piffer, S; Lorini, R; Minuto, N; Roncarolo, F; Tenconi, T; Predieri, Barbara; Reali, Mf; Medici, A; Biagioni, M; Gesuita, R; Santeusanio, F; De Giorgi, G; Visalli, N; Bizzarri, C; Chiarelli, F; Tumini, S; Prisco, F; Confett, S; Frongia, P; Marinaro, A. M.
abstract

AIMS: Several studies confirmed the growing rate of Type 1 diabetes mellitus in childhood coinciding with increasing diagnosis of viral infections. A study investigating the incidence of Type 1 diabetes during 1996-1997 showed a higher notification of viral infections in the Pavia District. The aim was to confirm these results. METHODS: This study evaluated the relationship between new cases of Type 1 diabetes and those of measles, mumps and rubella in 1996-2001, analysing data of newly-diagnosed Type 1 diabetes children, aged 0-14 years and enrolled into the RIDI (Italian Insulin-dependent Diabetes Registry) during the same years. Measles, rubella and mumps rates were calculated using as denominator the estimated 'population at risk', represented by the number of 0- to 14 year-old subjects who did not undergo the MMR (measles, mumps and rubella) vaccination. In order to investigate the association between Type 1 diabetes incidence and measles, rubella and mumps respectively, Spearman's rank correlation was used. RESULTS: The analysis of the whole Registries data did not at first show any statistical significance between age-standardized Type 1 diabetes incidence density and estimated rates of measles, mumps and rubella notifications. Excluding data from Sardinia Registry, a significant association was observed between Type 1 diabetes incidence and mumps (P = 0.034) and rubella (P = 0.014), respectively, while there was no statistical significance between the incidence of measles cases and diabetes rates (P = 0.269). CONCLUSIONS: According to our findings, mumps and rubella viral infections are associated with the onset of Type 1 diabetes. The statistical significance observed after exclusion of the Sardinian data suggests that other environmental factors may operate over populations with different genetic susceptibility.

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 - 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 - 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 - 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 - 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 - 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)

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 - 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 - GeNeSIS in Italy: Baseline Features of the Population and Preliminary Data on Outcomes. [Abstract in Rivista]
Tauchmanova, L; Predieri, Barbara; Cicognani, A; Cappa, M; De Luca, F; Vanelli, S; Bona, G; D'Avanzo, Mg; Loche, S; Valle, D.
abstract

N.A.

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 - 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 - 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 - 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 - 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 - 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 - 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.

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 - 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 - 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 - Lipide profile, antioxidant factors and endothelial function in children and adolescent with type 1 diabetes mellitus [Abstract in Rivista]
L., Iughetti; A., Lasagni; Bergamini, Barbara Maria; Rossi, Rosario; P., Appio; A., Nuzzo; Modena, Maria Grazia; Salvini, Annamaria; Lami, Francesca; Bruzzi, Patrizia; Vellani, Giulia; Patianna, VIVIANA DORA; Predieri, Barbara
abstract

Type 1 diabetes mellitus (T1DM) is associated with the development of micro- and macro-vascular complication generally related to the duration of disease and glycemic control. Chronic hyperglycemia increases production of free radical intermediates which in turn augments oxidative stress. The oxidative stress can play a key role in the development of diabetic complications affecting also vascular function.In this study we evaluated the lipid profile, the parameters related to oxidative stress and the endothelial function to assess the relationships between these parameters and metabolic control in children and adolescents with T1DM. A total of 58 T1DM patient (11,5±3,49 yr) and 36 healthy children (9,60±3,21 yr) were studied.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 (VitE), beta-carotene, lycopene, retinol, Vitamin C reduced (Vit C-Red) and oxidized (VitC-Oxid) and hemoglobin glycosilated (HbA1c) were measured. Vascular function was assessed by measurement of endothelium-dependent vasodilatation of brachial artery (FMD) using a high-sensibility of ultrasound system. There were no significant difference in the levels of TC, LDL-C and HDL-C between diabetic patients and the controls. Serum concentrations of TG in T1DM subjects were significantly lower than in control ones. Total antioxidant status (VitE, beta-carotene, lycopene, retinol, Vit C-Red) don't showed significant difference between groups. Only levels of VitC-Oxid were significant higher in patiens with T1DM. Moreover, prepuberal T1DM subjects showed higher MDA serum concentration than controls (p<0,01). FMD (7.99±1.06%) was impaired in 46% of T1DM subjects. There was negative correlation between FMD and serum levels of LDL-C. In our T1DM patients the glycemic control (mean value of HbA1c= 8,33%) was associated with normal lipid profile and normal antioxidant levels. Despite of these data diabetic patients show increased oxidative parameters (MDA, VitC-Oxid). Even if FMD was not apparently related to antioxidant status, the relationship with lipid values emphasizes the role of a global metabolic control to optimize the vascular health of these patients.

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 - 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 - 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 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 - 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 - 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 - 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 - 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 - 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 (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 - Deficit di ormone della crescita e malattia celiaca. [Capitolo/Saggio]
Iughetti, Lorenzo; F., Pellicanò; Vellani, Giulia; 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 - IperCPKemia e tiroidite linfocitaria. [Capitolo/Saggio]
Iughetti, Lorenzo; F., Pellicanò; Vellani, Giulia; Predieri, Barbara
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 - 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 - 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 - 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 - 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 - 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 - Diventare obesi [Articolo su rivista]
Iughetti, Lorenzo; Madeo, S; Stendardo, A; Predieri, Barbara
abstract

N.A.

2006 - Genetic and therapeutic aspects of familial hypercholesterolemia in childhood and adolescence [Capitolo/Saggio]
Iughetti, Lorenzo; Predieri, Barbara; PRIORE OLIVA, Claudio; L., Viola; S., Bernasconi; F., Balli; S., Calandra
abstract

N.A.

2006 - Growth hormone impaired secretion and antipituitary antibodies in patients with coeliac disease and poor catch-up growth after a long gluten-free diet period: a causal association? [Articolo su rivista]
Iughetti, Lorenzo; DE BELLIS, A; Predieri, Barbara; Bizzarro, A; DE SIMONE, M; Balli, Fiorella; Bellastella, A; Bernasconi, S.
abstract

Introduction Coeliac disease (CD) is usually associated with impaired growth in children. A gluten-free diet (GFD) induces a catch-up growth with the recovery of height in about 2 years.Aim and discussion The lack of the height improvement has been related to growth hormone (GH) secretion impairment. CD is an autoimmune disease often associated with other endocrine and non-endocrine autoimmune disease. The aim of this study was to evaluate antipituitary autoantibodies (APA) and antihypothalamus autoantibodies in CD children with poor clinical response to a GFD and growth hormone deficiency (GHD). We diagnosed CD on the basis of specific antibodies and endoscopic biopsies in 130 patients aged 1–15 years. Seven CD children, without catch-up growth after at least 12-months GFD, were tested for GH secretion and, in five out of seven patients, the diagnosis of GHD was made in the absence of metabolic and systemic diseases.Results APA and antihypothalamus antibodies were detected by the indirect immunofluorescence method in the seven CD children without catch-up growth factor and in 25 CD children without growth impairment matched for sex and age, and in 58 healthy children as control groups. APA resulted positive at high titres in four out of five CD-GHD patients and were also positive at low titres (<1:8) in three of only CD children and in two out of 58 controls. Hypothalamic-pituitary magnetic resonance imaging (MRI) was normal in all patients except in one with cystic pineal. APA have been previously detected not only in adults with GHD, but also in idiopathic GHD children, suggesting the occurrence of an autoimmune hypophysitis in these patients.Conclusion In our study, the presence of APA in CD children without catch-up growth after GFD seems to be able to identify an autoimmune form of hypophysitis involving the somatotrophs cells.

2006 - Is short stature in Myhre syndrome related to growth hormone neurosecretory dysfunction? [Abstract in Rivista]
Iughetti, Lorenzo; Garavelli, L; Caselli, G; Predieri, Barbara; Banchini, G; Bernasconi, S.
abstract

Myhre syndrome (MS) is a very rare condition described in 1980 characterised by facial dysmorphism, brachydactyly, musclehypertrophy, decreased joint mobility, hearing loss, mental retardation, and short stature. The pattern of inheritance and the genemutations of MS are unknown. All reported patients were sporadic and paternal age was increased in half of the cases, suggestingdominant new mutations. We present a case with clinical findings typical for MS whose short stature might be partially related to GHneuro-secretory dysfunction. M.U., male, karyotype 46,XY, born at 37 weeks of gestation (BW 2.225 kg), was admitted to geneticevaluation for dysmorphic features. He had short palpebral fissures, maxillary hypoplasia, prognathism, small mouth, brachydactyly,muscle hypertrophy, decreased joint mobility, hearing loss, mental retardation and short stature. X-rays showed a thickened calvarium,broad ribs, hypoplastic iliac wings, large vertebral pedicles. The phenotype was very consistent with the diagnosis of MS. An accuratedifferential diagnosis ruled out similar dysmorphic conditions (Geleophysic dysplasia, acromicric dysplasia, OSMED, GOMBO, Moore-Federman syndromes). At 7.6 years of age because of a progressive impairment of height (cm 108, centile 0.2, -2.89 SDS) anendocrinological evaluation was performed. The hypothalamic-pituitary-IGF-1 axis (HP-IGF-1 axis) was investigated measuring baselineIGF-1 levels and spontaneous 24-hour GH profile by multiple sampling. The low IGF-1 levels (135 ng/ml) and the value of 24-hour GHprofile (2.13 ng/ml) were consistent with the condition of neurosecretory dysfunction. Disturbances of HP-IGF-1 axis were alreadyreported in subjects with MS but, to our knowledge, this is the first case of MS in whom a GH neurosecretory dysfunction has beendetected. Even if in this syndrome short stature is largely attributable to skeletal dysplasia, the impaired GH secretion may play a role inthe alteration of growth, suggesting the possibility that a GH therapy can improve the final height of these patients.

2006 - L'iposcultura e mastoplastica riduttiva con tecnica round block nel trattamento della ginecomastia in età pediatrica. [Relazione in Atti di Convegno]
Pl, Ceccarelli; M., Pinelli; Iughetti, Lorenzo; Predieri, Barbara; D., Biondini; Cacciari, Alfredo
abstract

non disponibile

2006 - Le obesità secondarie. [Articolo su rivista]
Predieri, Barbara; Madeo, Simona Filomena; Iughetti, Lorenzo
abstract

N.A.

2006 - The effect of growth hormone (GH) treatment in children with celiac disease (CD), antipituitary antibodies (APA) and growth hormonedeficiency (GHD) [Abstract in Rivista]
Iughetti, Lorenzo; A., De Bellis; Predieri, Barbara; A., Bellastella; A., Bizzarro; S., Madeo; L., Saviano; F., Balli; S., Bernasconi
abstract

GH treatment improves height growth rate in our patients, maintaining a significant efficacy along 2 years. Our results confirm that APA are detectable in CD patients with GHD suggesting an involvement of autoimmune mechanisms in the lack of height improvement after GFD. These patients could benefit by precocious hormonal therapy, interrupting the progression towards a stable clinical disease.

2006 - Thyroid function in children treated with antiepileptic drugs [Abstract in Rivista]
Predieri, Barbara; Madeo, S; Torelli, P; Guerra, A; Balli, Fiorella; Bernasconi, S; Giuva, Tiziana; Iughetti, Lorenzo
abstract

n.a.

2006 - Tracheobronchial anomalies in chromosome 22q11.2 microdeletion [Articolo su rivista]
Bertolani, Mf; Bergamini, Barbara Maria; Predieri, Barbara; Mirmassoumi, S; Bertolani, P; Sacco, O; Ferrari, Paola
abstract

No Abstract

2005 - Allopregnanolone levels decrease after LHRH analogue stimulation test in girls with central precocious puberty [Abstract in Rivista]
Predieri, Barbara; E., Casarosa; E., Farinelli; S., Luisi; F., Antoniazzi; F., De Luca; S., Bernasconi; Iughetti, Lorenzo
abstract

Allopregnanolone (AP), a neuroactive steroid secreted by central nervous system, adrenals, and gonads, plays a role in the development of precocious puberty, as demonstrated by its high baseline levels found in girls with central precocious puberty (CPP). In these patients AP concentrations significantly increase after LHRH stimulation test suggesting its ovarian origin. Aim of this study is to evaluate AP concentrations after LHRH and LHRHa stimulation test in girls with CPP to better establish the secretion source of this neurosteroid.Gonodotropins and steroid hormones were evaluated after LHRH and LHRHa stimulation test in 12 normal weight girls with CPP (PH and B 2-3, 8.06±0.73 yr., first pubertal signs appeared at 7.06±0.71 yr., bone age advanced of 1.91±0.74 yr., and LH levels >5 mUI/ml after both LHRH and LHRHa stimulation).After LHRH stimulation LH, FSH, and AP concentrations significantly increased in all patients. After LHRHa administration LH, FSH, and E2 levels significantly increased, while AP concentrations significantly decreased in all subjects (1.10±0.26, 0.89±0.29 nmol/l; P=0.001). The different response of AP to LHRH (increased levels) and LHRHa (decreased levels) reflect the agonist and antagonist action exerted by these secretagogues. Our data strongly suggest a direct action of LHRHa on ovaries independent of the pituitary, confirming the prevalent ovarian AP production in CPP subjects.

2005 - Altri fattori: obesità legata a farmaci [Capitolo/Saggio]
Iughetti, Lorenzo; Predieri, Barbara
abstract

N.A.

2005 - Diabetes duration and glycaemic control have a different effect on endothelial dysfunction in children with type 1 diabetes. [Abstract in Rivista]
Rossi, Rosario; Cioni, E; Nuzzo, A; Iughetti, Lorenzo; Predieri, Barbara; Modena, Maria Grazia
abstract

N.A.

2005 - Fattori sociali e ambientali [Capitolo/Saggio]
Predieri, Barbara; G., Caselli; Iughetti, Lorenzo
abstract

N.A.

2005 - Increased liver enzymes and hormonal therapies in girls and adolescents with Turner syndrome [Articolo su rivista]
Wasniewska, M; Bergamaschi, R; Matarazzo, P; Predieri, Barbara; Bertelloni, S; Petri, A; Sposito, M; Messina, Mf; De Luca, F; Italian Study Group for Turner, Syndrome
abstract

Elevated liver enzymes can be seen relatively frequently in patients with Turner syndrome (TS), while the pathogenesis of this remains unclear. Our epidemiological and prospective study aimed to investigate : a) the natural 2-yr course of liver disease in a selected cohort of young patients with TS, who had been preliminarily recruited on the basis of persistently elevated liver enzymes; b) the role of prolonged hormonal therapies in the etiology of liver dysfunction. From an overall population of 214 TS patients younger than 20 yr, only 19 (8.9%) were recruited, according to the following inclusion criteria: increased serum concentrations of one or more liver enzymes, exceeding the uppermost limit of the respective normal ranges, and persistence of these liver alterations for 6 months after the preliminary assessment. On the basis of the results of this prospective study, we can conclude that: a) the prevalence of liver abnormalities in girls and adolescents with TS is much lower and more strictly related to hormonal therapies than in TS adults; b) both autoimmunity and obesity are not frequently involved in the etiology of TS liver dysfunction; c) liver damage is either mild or moderate and its severity is not conditioned by karyotype; d) its course may be self-limiting; e) its natural history may be characterized in some cases by a slight deterioration of intrahepatic cholestasis, with no negative repercussions on liver synthetic function.

2005 - Iperisulinismo congento [Relazione in Atti di Convegno]
Predieri, Barbara; Cattani, S; Garetti, E; Ceccarelli, Pl; Madeo, S; Stendardo, A; Della Casa, E; Balli, F; Bernascono, S; Ferrari, Fabrizio; Iughetti, Lorenzo
abstract

No abstract

2005 - Ipoglicemia neonatale e labetalolo [Articolo su rivista]
Gargano, G; Lugli, L; Mariotti, I; Della Casa, E; Gallo, C; Roversi, Mf; Mordini, B; Predieri, Barbara; Iughetti, Lorenzo; Ferrari, Fabrizio
abstract

No abstract

2005 - Ipoglicemia transitoria in nato da madre ipertesa in terapia con labetalolo [Relazione in Atti di Convegno]
Lugli, L; Gargano, G; Sturloni, N; Cattani, C; Pagano, R; Grimaldi, R; Guagliumi, C; Predieri, Barbara; Iughetti, Lorenzo; Ferrari, Fabrizio
abstract

No abstract

2005 - L'approccio terapeutico al bambino e all'adolescente obeso [Articolo su rivista]
Iughetti, Lorenzo; Predieri, Barbara; Stendardo, Antonietta; Madeo, Simona Filomena
abstract

N.A.

2005 - Lack of growth recovery and growth hormone deficiency in patients with coeliac disease after a prolonged time-span of gluten free diet can be caused by an autoimmune hypophysitis. [Abstract in Rivista]
Iughetti, Lorenzo; A., De Bellis; Predieri, Barbara; A., Bellastella; A., Bizzarro; A., Stendardo; S., Madeo; F., Balli; S., Bernasconi
abstract

In the paper the authors hipothesize that lack of growth recovery and growth hormone deficiency in patients with coeliac disease after a prolonged time-span of gluten free diet can be caused by an autoimmune hypophysitis.

2005 - Lack of growth recovery and persistence of growth hormone deficiency in patients with coeliac disease after a prolonged time-span of gluten free diet can be caused by an autoimmune hypophysitis [Abstract in Rivista]
Iughetti, Lorenzo; A., De Bellis; Predieri, Barbara; S., Madeo; A., Stendardo; A., Bizzarro; A., Bellastella; F., Balli; S., Bernasconi
abstract

Coeliac disease (CD) has a negative influence on growth in children; however, the institution of gluten free diet (GFD) significantly improves height and weight velocity, so that height shows a full catch-up within about 2 years, even if it does not always happen. The absence of catch-up growth has been related to an impaired growth hormone (GH) secretion due to hypothalamic dysfunction. In CD patients some autoimmune endocrine alterations have been demonstrated and recently the occurrence of autoimmune hypophysitis has been suggested. Aim of this study is to investigate whether a poor auxological response to GFD with persistence of GH deficiency in a group of CD patients could be due to a coexistence of an autoimmune hypophysitis. Seven out of 130 CD patients were selected on the basis of poor catch-up growth (height < - 2 SDS) after 2 years of good adherence to a GFD as demonstrated by the negativity of the specific immune markers. All patients were submitted to blood sample collection to study the GH secretion after 2 different stimuli (arginine, clonidine, or L-DOPA) and to search for auto-antibodies against hypothalamus and hypophysis by immunofluorescence method. A decreased GH-stimulated secretion (<10 ng/ml) was demonstrated in 5 cases out of 7 CD children with poor catch-up growth and 4 of them resulted strongly positive for auto-antibodies against hypothalamus and hypophysis. Cerebral and hypophyseal NMR was normal in all children.Our study confirms the existence in some CD patients of a persistent GH secretion impairment causing a poor statural catch-up growth also after GFD. Moreover, our data strongly suggest that this impairment can have an autoimmune origin and that in patients with CD the occurrence of this autoimmune disturbance is more frequent than that so far thought. This has to lead to a more accurate evaluation of endocrine autoimmunity in these patients.

2005 - Low serum allopregnanolone levels in girls with precocious pubarche [Articolo su rivista]
Iughetti, Lorenzo; Predieri, Barbara; Luisi, S; Casarosa, E; Bernasconi, S; Petraglia, F.
abstract

Allopregnanolone, a neuroactive steroid, increases during pubertal development and high concentrations are present in subjects with precocious puberty. The aim of the present study was to evaluate serum allopregnanolone levels in girls with precocious pubarche (PP). Basal gonadotropins and steroid hormones were assessed in 17 girls with PP, 22 girls with central precocious puberty (CPP), 25 girls with normal puberty at the same pubertal stage of CPP ones, and 17 prepubertal girls. Adrenocorticotropin hormone (ACTH) and gonadotropin-releasing hormone (GnRH) stimulation tests were performed in all subjects with PP, and in 12 out of 22 with CPP All girls with normal puberty underwent to GnRH test, while ACTH test was performed in 17 out of 25. Basal dehydroepiandrosterone sulfate (DHEAS) concentrations resulted significantly higher in PP and normal pubertal girls than in prepubertal ones. Allopregnanolone, gonadotropins and estradiol levels were significantly lower in PP group with respect to CPP (P < 0.05), while they were comparable among PP, normal pubertal and prepubertal groups. After ACTH administration, allopregnanolone concentrations significantly increased in all groups (P < 0.05). After GnRH stimulation, its levels significantly increased in CPP and normal pubertal controls (P < 0.05), while no incremental rise was found in PP girls. In conclusion, our study shows that in girls with PP basal and GnRH-stimulated levels of allopregnanolone are significantly lower than in CPP girls. These data suggest that this neurosteroid may be considered a new marker of pubertal development.

2005 - Neuroradiological alterations in patients with Prader-Willi syndrome - [Abstract in Rivista]
Iughetti, Lorenzo; L., Bosio; A., Corrias; L., Gargantini; L., Ragusa; C., Livieri; Predieri, Barbara; G., Caselli; G., Grugni
abstract

Prader-Labhart-Willi syndrome (PWS) is a genetic disorder caused by an alteration of the long arm of paternal chromosome 15 (by deletion, micro deletion, maternal uniparental disomy, mutation of imprinting centre, chromosomal rearrangement). PWS is characterized by hypotonia, short stature, uncontrollable hyperphagia and obesity, hypogenitalism, temperature instability, and cognitive impairment). Although no specific lesion of the hypothalamus has been demonstrated in PWS necropsy reports, hyperphagia, hypogonadism, and deficit of growth hormone suggest a possible central hypothalamic/pituitary dysfunction in these subjects.In this study we retrospectively analyse the cerebral magnetic resonance images (MRI)of a group of patients with PWS to evaluate the size of the anterior pituitary gland and the presence of neuroradiological alterations.In conclusion we believe that a neuradiological evaluation seems to be indicate in all PWS patients.

2005 - Valutazione dell'apporto dietetico [Capitolo/Saggio]
Iughetti, Lorenzo; S., Madeo; A., Stendardo; Predieri, Barbara
abstract

N.A.

2005 - Vascular endothelial function in children with familial hypercholesterolemia [Abstract in Rivista]
Predieri, Barbara; A., Nuzzo; L., Laudizi; S., Madeo; A. L., Quitadamo; A., Stendardo; F., Balli; Modena, Maria Grazia; Iughetti, Lorenzo
abstract

Impaired endothelial function is detectable in patients with disease associated with vascular complications, such as familial hypercholesterolemia (FH). Impaired endothelial function, assessed as flow mediated dilation (FMD) of the brachial artery, can predict future cardiovascular disease (CVD). In the present study we evaluate whether children with FH are characterized by an impairment of endothelial function and if there are differences between children with and without familial CVD.Fifteen heterozygous FH children (10 girls and 5 boys) age 9.31±3.39 yr., were enrolled in the study. In all subjects FH diagnosis was made by family history, clinical and laboratory findings, and it was confirmed by detection of a mutation in the LDL receptor gene. Vascular function of conduit arteries was assessed by measurement 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.Plasma total cholesterol and low-density lipoprotein levels were above the 95th percentile for age and gender (329.9±47.5 and 257.0±36.7 mg/dl, respectively). Only in 1 out of 15 children FMD impairment was demonstrated (FMD <7%; mean FMD 16.0±6.6%). Moreover, no difference in FMD between FH children with versus without CVD in the family history was revealed (13.5±6.78 and 20.1±4.78%, respectively; P=0.19). A significant correlation between FMD and chronological age of children was found (r=-0.75; P=0.03).Our data suggest that FH children have an endothelial function comparable to matched control children reported in other studies. We demonstrate that in childhood the degree of FMD is not already associated with the presence of a family history for CVD. However, the negative correlation between FMD and chronological age suggests a progressive damage of endothelial function that apparently appears in later life. Further studies are required to understand if there are factors able to delay the beginning of endothelial dysfunction.

2004 - Diabetes incidence in 0- to 14-year age-group in Italy: a 10-year prospective study [Articolo su rivista]
Carle, Flavia; Gesuita, Rosaria; Bruno, Graziella; Coppa, Giovanni V; Falorni, Alberto; Lorini, Renata; Martinucci, Marco E; Pozzilli, Paolo; Prisco, Francesco; Songini, Marco; Tenconi, Maria T; Cherubini, Valentino; RIDI Study Group (Piffer, S; Franchini, S; Bianchi, L; Cerutti, F; Merletti, F; Pagano, G; Cotellessa, M; Minicucci, L; Barbieri, P; Devoti, G; D’Annunzio, G; Bazzano, S; Toni, S; Reali, Ms; Medici, A; Iughetti, L; Predieri, B; Balli, F; Visalli, N; Sebastiani, L; Marietti, G; Santeusanio, F; De Giorgi, G; Santilli, E; Iannilli, A; Pinelli, A; Mascioli, G; Altobelli, E; Chiarelli, F; Tumini, S; Iafusco, D; De Felice, E; Ingenito, N; Casu, A; Frongia, P; Marinaro, A)
abstract

The Registry for Type 1 Diabetes Mellitus in Italy (RIDI) Study Group was established to coordinate the registries of type 1 diabetes in Italy. This report is based on 3,606 children younger than 15 years diagnosed with type 1 diabetes and prospectively registered during 1990-1999 by nine centers, covering >35% of the Italian population.

2004 - Familial Hypobetalipoproteinemia Due to a Novel Mutation of Apolipoprotein B Gene " - Horm Res 2004; [Abstract in Rivista]
Iughetti, Lorenzo; Tarugi, Patrizia Maria; A., Tozzola; Predieri, Barbara; S., Lancellotti; F., Balli; S. B., Calandra
abstract

Since in most of the introns of the human gene A is present in this position it is likely that the presence of a G in this position, like in our patient, disrupts the splicing process.This hypothesis is supported by the observation that proband’s sister who has also hypobetalipoproteinemia was carrier of the same mutation in intron 8. This mutation has not yet been found in normal subjects and in more than 30 FHBL individuals investigated by our group.In FHBL the variability in symptoms was related to the length of the truncated apoB and its ability to form chylomicrons and absorb fat-soluble vitamins and essential fatty acids rather than the levels of LDL-C). Our patient belongs to our series of “symptomatic” heterozygous FHBL subjects with no truncated apoBs detectable in plasma. This finding raises the question as to whether, in a specific FHBL patient/pedegree, hypobetalipoproteinemia is due to mutation in the APOB gene or in other genes (yet to be identified) affecting apoB metabolism. Probably, hypobetalipoproteinemia explains the presence of liver steatosis already at this age, even if it cannot be excluded that obesity should play a role in this alteration.

2004 - Focal Hyperinsulinism Due to 2 Novel Paternally Derived Mutations in SUR1 and Kir 6.2 [Abstract in Rivista]
Iughetti, Lorenzo; K., Hussain; Predieri, Barbara; S., Cattani; E., Garetti; K., Nanto Salonen; Ferrari, Fabrizio; F., Balli; S., Bernasconi
abstract

Persistent hyperinsulinemic hypoglycaemia of infancy (PHHI) is heterogeneous condition often due to focal adenomatous hyperplasia of the pancreas. Secretion of insulin is unregulated, resulting in profound hypoglycemia. Mutations in the genes of both subunits of the betacell KATP channel, Kir6.2 (potassium channel) and SUR1 (sulfonylurea receptor) have been associated with the autosomal recessive form of this disorder. Patients harboring SUR1 mutations often do not respond well to diazoxide (D). Generally in focal forms two paternal alleles are present with subsequent alteration of insulin secretion. The lesions can be cured by selective resection, but these lesions are difficult to detect. The definitive diagnostic tool are pancreatic venous sampling (PVS) and 18Fluoro L-DOPA>positron emission tomography (PET-DOPA). Patient was born at term (BW 4.1 kg), soon after birth he developed hypoglycemia occasionally symptomatic with tremors and hypotonia, required increased glucose therapy (9mg/kg/min, i.v.) despite milk administration (75cc/kg/day). No response to glucagon (0.5mg/kgday i.v.) and D (20mg/kg/day, per os). Good response to octreotide injections (32.2 microgr/kg/day, s.c.). Pancreatic biopsy, genetic study and PET<ndash>DOPA were performed. Pancreatic biopsy on our patient shows normal <beta><ndash>cell nuclei, no evidence of diffuse disease. Genetics demonstrated he has 2 paternally derived mutations in SUR1 and Kir 6.2, causing abnormal insulin secretion (which type of mutation?). The whole body examination with PET<ndash>DOPA scan demonstrated a very intensive focus in the uppermost area of the corpus of the pancreas.In our patient, as suspected by no response to D, SUR1 mutation was demonstrated. Moreover, like our child, we suggest that all patients with PHHI D resistant should have PET-DOPA that represents a noninvasive method for the identification and localisation of focal PHHI. Focal forms of PHHI should be operated because complete cure without risk of diabetes.

2004 - Relationship between body mass index and insulin measured during oral glucose tolerance testing in severely obese children and adolescents [Articolo su rivista]
Iughetti, Lorenzo; De Simone, M; Bernasconi, Sergio; Predieri, Barbara; Battistini, Nino Carlo; Bedogni, G.
abstract

Primary objective: The study evaluated the accuracy of body mass index (BMI) in detecting hyperinsulinaemia during oral glucose tolerance testing (OGTT) in severely obese children. Research design: A cross-sectional study was carried out. Materials and methods: A total of 118 obese children and adolescents (49 females and 69 males) aged 6-19 years were consecutively studied at an outpatient paediatric clinic. Hyperinsulinaemia was defined as a value of log-transformed fasting insulin greater than or equal to80th percentile and OGTT hyperinsulinaemia as a value of the log-transformed area under the curve (AUC) of insulin greater than or equal to80th percentile. The study hypothesis was tested using a logistic regression model with hyperinsulinaemia as the outcome variable and the z-score of BMI corrected for age (z-BMIage) as the predictor variable. Receiver-operator characteristic (ROC) curves were used to evaluate accuracy. Results: The mean (SD) BMI for age of the children was 28.6 (4.0) kg m(-2), corresponding to 2.2 (0.5) standard deviation scores. The odds ratio (OR) of OGTT hyperinsulinaemia was 2.0 (95% CI 1.2-3.3; p = 0.007) for each unit increase of z-BMIage and the corresponding ROC-AUC was 0.74 (95% CI 0.61-0.86; p = 0.0001). In comparison, the OR of fasting hyperinsulinaemia was 1.1 (95% CI 0.7-1.7; p = 0.716) for each unit increase of z-BMIage and the corresponding ROC-AUC was 0.49 (95% CI 0.35-0.62; p = 0.863). Conclusion: BMI is reasonably accurate in detecting OGTT hyperinsulinaemia in severely obese children.

2004 - Short stature with chromosome aberrations [Capitolo/Saggio]
Iughetti, Lorenzo; Milioli, S; Mariani, S; Predieri, Barbara; Bernasconi, S.
abstract

no abstract

2004 - TWO YEARS FOLLOW-UP OF GROWTH HORMONE (GH) THERAPY IN SHORT STATURE CHILDREN WITH REDUCED GH BIOACTIVITY. [Abstract in Rivista]
Predieri, Barbara; Iughetti, Lorenzo; A., Stendardo; P., Travaglino; E., Bozzola; M., Bozzola; S., Bernasconi
abstract

Biologically inactive growth hormone (GH) due to genetic mutations is a rare cause of short stature, characterized by the lack of GH action despite its normal immunoreactivity. We studied 10 boys (aged 9.60±2.78 yr., 23.1±7.6 kg, BMI 15.35±1.92 kg/m2 and bone age 7.65±2.75 yr.) with short stature, reduced growth velocity (GV) and discordant GH responses to standard provocative tests. On the basis of the reduced GH bioactivity, demonstrated by Nb2 bioassay, all children were treated with GH (0.24 mg/kg/week). Aim of our study was to evaluate the effect of GH therapy in these children. All results are reported as the mean±SDS. Student’s t test for paired samples was used for comparison of data between before and after 12 and 24 months of therapy (* p<0.05).GH treatment significantly improves auxological and laboratory data of our patients such as treated GHD subjects. The positive effect obtained during the first year of therapy persists in the second year.

2004 - Younger age at diagnosis of type 1 diabetes mellitus in children of immigrated families born in Italy. [Articolo su rivista]
Cadario, F; Vercellotti, A; Trada, M; Zaffaroni, M; Rapa, A; Iafusco, D; Salardi, S; Baldelli, R; Bona, G; Rigardo, S; Lera, R; Cherubini, V; Francolini, S; Fifi, A; Scaramuzza, A; Cavallo, L; Zucchini, S; Corbelli, E; Gallo, F; Zedda, Ma; Angius, E; Ripoli, C; La Loggia, A; Scalia, G; Cicchetti, M; Macchiaroli, A; Oteri, F; Pocecco, M; Cerasoli, G; Sperlì, D; Montaldo, M; Startari, L; Vergerio, A; Banin, P; Martinucci, M; Toni, S; Mastrangelo, C; Lorini, R; D'Annunzio, G; Cotellessa, M; Minicucci, L; Pescarmona, M; Di Quinci, M; Lombardo, F; Iughetti, Lorenzo; Predieri, Barbara; Boccato, S; Prisco, F; Mongiotti, C; Cardella, F; Vanelli, M; Chiari, G; Zanasi, P; Larizza, D; Borghesi, A; De Giorgi, G; Calisti, L; Menchini, S; Marsciani, A; Pausini, L; Patera, P; Crinò, A; Cerutti, F; Sacchetti, C; Rabbone, I; Fontana, F; Giorgetti, R; Trussi, G; Cauvin, V; Gargantini, L; Tenore, A; Zanatta, M; Salvatoni, A; Fusari, M; Araldi, C.
abstract

The aim of this study was to evaluate the age of immigrants' children at diagnosis of Type 1 diabetes (T1DM) according to their country of birth. Immigration from developing countries to a westernised area causes rapid changes in the environmental conditions, and we investigated whether the location of birth, either inside or outside Italy, is associated with age at diagnosis of diabetes. Out of a prevalent hospital-based cohort of 5718 T1DM children cared for in 2002 in 47 Italian Pediatric Diabetes Units, we recruited 195 children (M: 97) of immigrants from developing countries - 119 were born in Italy and 76 outside the European Union. Children with only one immigrant parent (no. 42) were also included. Age at diagnosis of T1DM, and other variables were compared with those of Italian children. Children of immigrated families born in Italy developed T1DM at a median age of 4.0 yr (IQR 2.2-6.9), whereas those born in developing countries and that had immigrated to Italy after birth developed T1DM at a median age of 7.9 yr (IQR 5.1-10.7, p<0.001). Among the children born in Italy, 77 had parents who were both immigrants and the children's median age at diagnosis was 3.8 yr (IQR 2.1-6.3); 42 had only one immigrant parent and, when it was the father (no.=23), median age was even younger (2.9 yr, IQR 2.0-8.2). Ten children had immigrated in their first yr of life and their median age was 9.1 yr (IQR 5.0-10.6). The median age of the Italian children was 6.6 yr (IQR 3.6-9.5). Results show that the outbreak of T1DM is earlier in immigrants' children born in Italy than in original countries.

2004 - ascular Endothelial Function and Glycemic Control in Girls with Type 1 Diabetes; [Abstract in Rivista]
Predieri, Barbara; Iughetti, Lorenzo; Rossi, Rosario; A. C., Nuzzo; E., Cioni; F., Balli; Modena, Maria Grazia
abstract

N.A.

2003 - "Balanced translocation" T(3;11)(P21;Q13) in a lipoma from a girl with suspected MEN 1 Syndrome. [Abstract in Rivista]
Predieri, Barbara; Iughetti, Lorenzo; M., Losa; L., Larizza; O., Rodeschini; D., Giardino; E., Valtorta; P., Finelli; S., Bernasconi
abstract

Lipomas are the most common soft tissue tumors in man. Non-random chromosomal rearrangements have been demonstrated in a high proportion of these benign tumors. Lipomatous tumors are known to occur in a relatively high proportion of patients with MEN 1. We report on a chromosome study of a subcutaneous lipoma, developed by a girl 14 year-old with a history of MEN 1 (stunted growth, bilateral hemianopsia, primary hyperparathyroidism and prolactin-secreting macro pituitary adenoma), localized to the internal surface of the right thigh. Mutation screening of MEN 1 gene (exons 2-10) by DGGE and direct sequencing didn't evidence sequence alteration. However, involvement of the gene can not yet be ruled out. The lipoma (3x1.3 cm) in a short time increased its dimension and another one was detected in abdomen. At the histopathological analysis it was defined as spindle cell lipoma. Cytogenetic analysis performed on direct and short-term cultures revealed a 46,XX,t(3;11)(p21;q13) karyotype in all the metaphases analyzed. Involvement of the 11q13 band in chromosomal rearrangements associated with lipoma has been rarely observed and no lipomas have been described where the 3p21 band, partner of the observed apparently balanced reciprocal translocation, is affected. Findings on mutations of the menin gene in a few MEN 1-assoiated lipomas and loss of heterozygosity at 11q13 in sporadic lipomas have stimulated the hypothesis that lipomas may belong to the group of tumors caused by defects of the MEN 1 gene. Given that controversial evidence has been so far provided on the involvement of the menin gene in lipoma formation in the context of MEN 1 syndrome, we aim at investigating whether or not this gene is disrupted by the 11q13 breakpoint observed in our patient. FISH characterization of the genomic regions involved in the chromosome breakage using BAC probes is in progress to precisely map the breakpoints and search for candidate genes involved in the pathogenesis of lipoma.

2003 - An ancient disease that can be prevented is returning: nutritional rickets [Abstract in Rivista]
S., Pedori; Iughetti, Lorenzo; M. E., Street; Predieri, Barbara; L., Cagozzi; A., De Martino; L., Garavelli; S., Bernasconi; R., Virdis
abstract

N.A.

2003 - Different levels of Allopregnanolone in girls with precocious pubarche and central precociuos puberty [Abstract in Rivista]
Predieri, Barbara; Iughetti, Lorenzo; L., Cobellis; S., Luisi; E., Casarosa; F., Petraglia; S., Bernasconi
abstract

N.A.

2003 - Growth Hormone (Gh) treatment usefulness in children with short stature due to Gh bioinactivity [Abstract in Rivista]
Iughetti, Lorenzo; Predieri, Barbara; A., Stendardo; E., Bozzola; S., Madeo; P., Travaglino; S., Bernasconi
abstract

Short stature caused by biologically inactive growth hormone (GH) is rare and characterized by lack of GH action despite its normal immunoreactivity. A dissociation between GH bioactivity and immunoreactivity is present in physiologic conditions, suggesting that standard GH measurements do not provide any information on the biologic activity of the hormone, evaluation that can be performed by the Nb2 cell bioassay. Moreover, the diagnosis of GH bioinactivity should be confirmed by a marked catch-up growth after exogenous GH administration. Aim of our study is to evaluate the activity of GH treatment in subjects with short stature, reduced growth velocity (GV), normal GH response to provocative tests and reduction of GH bioactivity. We studied 10 male, came to our attention for short stature and reduction of GV, aged 10.01±2.60 yr.; weight 24,7±7,5 kg, BMI 15.73±1.92 kg/m2 and bone age 8.17±2.64 yr. All subjects underwent standard GH stimulation tests and Nb2 bioassay that demonstrated the characteristics above described. They were submitted to GH treatment at a dose of 0.24 mg/kg/week.

2003 - L'orchidopessi videolaparoscopica secondo Fawler-Stephens in due tempi nel trattamento del testicolo endoaddominale alto [Abstract in Atti di Convegno]
Pl, Ceccarelli; Predieri, Barbara; M., Mordenti; A., Stendardo; J., Chiarolanza; A., Rizzo; L., Lugli; Iughetti, Lorenzo; F., Balli; Cacciari, Alfredo
abstract

non disponibile

2003 - Primary Hyperchylomicronemias in three patients from highly inbred ethnic groups: genetic and therapeutic aspects [Abstract in Rivista]
Iughetti, Lorenzo; PRIORE OLIVA, Claudio; Predieri, Barbara; M., Ghisellini; S., Bertolini; C., Wilson; S., Li Volti; F., Balli; Calandra, S.
abstract

During a genetic study of primary hypertriglyceridemias we analysed the genes encoding the enzyme lipoprotein lipase (LPL) and its activator the apolipoprotein C-II (apoCII) in 3 subjects with primary hypertriglyceridemia. Proband I, a 12 years-old boy, born from two first cousins from Morocco, had high plasma triglycerides (>2.000 mg/dl) associated with recurrent abdominal pain. The LPL gene sequence revealed that he was homozygous for a c.1032 T->A transversion in exon 7, which converts serine at position 259 into arginine (S259R). Although both parents and one sister were carriers of this mutation, only the father had hypertriglyceridemia. S259R substitution had been previously reported in hyperchylomicronemic patients of Berberian descent in Morocco. Proband II was a 11 months female from New-Zealand born from two second double-cousins of Maori descent. She had severe hypertriglyceridemia (>10.000 mg/dl) lipid infiltration of the retina and the central nervous system. LPL gene sequence was negative whereas the sequence of apo C-II gene revealed that she was homozygous for a c.1118 C->A transversion in exon 4 which converts the codon TAC (tyrosine at position 63) into TAA (stop) (Y63X). This new mutation results in a truncated apo C-II devoid of the LPL binding domain. This mutation introduces a new MseI restriction site; this allowed the rapid screening of the mutation in all family members. Proband III was a 5 year-old boy born from two first cousins from Morocco. The sequence of LPL and apo C-II genes in this case was negative indicating the presence of another gene affecting triglyceride metabolism. All subjects were treated with PUFA supplementation (3.4 g/day), obtaining a reduction (about 40%) of the triglycerides levels and a relief of the symptoms. Thus severe recessive hypertriglyceridemias due to rare mutations of LPL, apo C-II or other unknown genes are expected to occur in highly inbred ethnic groups and respond to the therapy with ω-3 fatty acids.

2003 - Treatment of childhood obesity [Obesità in età pediatrica: Trattamento] [Articolo su rivista]
Trifirò, G; Salvatoni, A; Tanas, R; Brambilla, P; Maffeis, C; Cammareri, V; Corciulo, N; Mulè, Rm; Peverelli, P; Cerutti, F; Rabbone, I; Saggese, G; Miniero, R; Bernasconi, S; Chiumello, G; Rondanini, Gf; Manzoni, P; Ambruzzi, Am; Morino, G; Cuccarolo, G; Del Majno, Um; Monetti, N; Martino, R; Grugni, G; Crinò, A; Ciampalini, P; Beccaria, L; Caselli, G; Balsamo, A; Cicognani, A; Greggio, Na; Modestini, E; Iughetti, Lorenzo; Predieri, Barbara; De Sanctis, V; Franzese, A; Yannakou, P; Guerraggio, L; Luciano, A; Livieri, C; Di Pietro, Me; Bergamaschi, G; Valerio, G; Grezzani, A.
abstract

This article provides current guidelines on the treatment and prevention of childhood obesity. Since factors involved in obesity change with age, the therapeutic approach in pre-school children will be different from pupils and adolescents. The treatment will also be modulated on the basis of weight excess, weight gain velocity and complications. The main goal of the treatment should be to encourage the child and his family to have healthy lifestyle. Families who are not ready for change might benefit from counselling to improve motivation before starting treatment. A detailed alimentary and behavioural history is the start point of the treatment. The strategy of the intervention is to induce changes at three levels: 1) attitudes of parents; 2) physical activity; 3) energy intake. The treatment of the adolescents should take into account the pubertal changes and the psychological aspects of this peculiar period of life. Obesity is a chronic disease and its treatment needs long-life follow-up. The long-term results of the obesity treatment are often disappointing and we have to consider consistent prevention programs for better results.

2002 - Alimentazione e stili di vita: compenso lipidco. [Articolo su rivista]
Iughetti, Lorenzo; Predieri, Barbara
abstract

N.A.

2002 - Changes of serumn allopregnanolone levelsa during GnRH analogue therapy in girls with central precocious puberty. [Abstract in Rivista]
Predieri, Barbara; Iughetti, Lorenzo; L., Cobellis; S., Luisi; E., Casarosa; S., Forese; F., Petraglia; S., Bernasconi
abstract

N.A.

2002 - Complex disease phenotype revealed by growth hormone deficiency associated with a novel mutation in the GH-1 gene [Abstract in Rivista]
Iughetti, Lorenzo; I., Netchine; S., Milioli; N., Thibaud; Predieri, Barbara; S., Amselem
abstract

n.a.

2002 - Determination of growth hormone bioactivity: a useful tool for short stature diagnosis. [Abstract in Rivista]
S., Milioli; Iughetti, Lorenzo; Predieri, Barbara; A., Stendardo; P., Travaglino; E., Bozzola; A., Tirendi; S., Bernasconi
abstract

N.A.

2002 - Genetica dell’ipercolesterolemia familiare. [Articolo su rivista]
Iughetti, Lorenzo; Predieri, Barbara; Calandra, S; Bernasconi, S.
abstract

N.A.

2002 - High serum allopregnanolone levels in girls with precocious puberty [Articolo su rivista]
Iughetti, Lorenzo; Predieri, Barbara; L., Cobellis; S., Luisi; M., Luisi; S., Forese; F., Petraglia; S., Bernasconi
abstract

Allopregnanolone, a circulating neuroactive steroid hormone, is involved in the modulation of behavioral functions, stress, and the neuroendocrine axis. The aim of this study was to evaluate serum allopregnanolone concentrations in girls with central precocious puberty (n = 12), girls with normal pubertal development at the same pubertal stage (n = 17), and prepubertal girls (age-matched; n = 16). Gonadotropin and steroid hormones (allopregnanolone, cortisol, dehydroepiandrosterone sulfate, and E2) were assessed in all patients. GnRH and ACTH stimulation tests were performed in all girls with central precocious puberty and in some pubertal controls. Basal allopregnanolone levels in girls with central precocious puberty were significantly higher than in normal controls (P &lt; 0.01). Allopregnanolone levels increased significantly after GnRH and ACTH stimulation tests (P &lt; 0.05) both in girls with central precocious puberty and in those with normal pubertal development. There was no difference found between the peak values. In conclusion, our study shows that allopregnanolone is hypersecreted in central precocious puberty, confirming a pubertal stage-related increase in its levels during normal pubertal development. The increase in serum allopregnanolone after GnRH and ACTH stimulation tests demonstrates that both adrenal cortex and gonads are sources of this neuroactive steroid.

2002 - Nanismo ipofisario da deficit di GH geneticamente determinato. [Articolo su rivista]
Iughetti, Lorenzo; Milioli, S; Predieri, Barbara; Cavalleri, F; Ferrari, P.
abstract

N.A.

2002 - Nutrient intake in diabetic (T1DM) children before and after nutritional couselling [Abstract in Rivista]
Iughetti, Lorenzo; Predieri, Barbara; M., Gavioli; S., Milioli; S., Bernasconi
abstract

N.A.

2002 - Phenotipic expression of familial hypercholesterolemia in children with different mutation of low-density lipoprotein receptor gene [Abstract in Rivista]
Iughetti, Lorenzo; Predieri, Barbara; A., Stendardo; L., Viola; F., Balli; S., Calandra
abstract

N.A.

2001 - Allopregnanolone levels after LHRH and ACTH administration in girls with precocious puberty. [Abstract in Rivista]
Iughetti, Lorenzo; Predieri, Barbara; L., Cobellis; S., Luisi; M., Luisi; S., Forese; S., Petraglia; S., Bernasconi
abstract

N.A.

2001 - Attività sportiva e sviluppo puberale [Articolo su rivista]
Iughetti, Lorenzo; Milioli, S; Predieri, Barbara; Bernasconi, S.
abstract

N.A.

2001 - Changes of allopregnanolone levels after LHRH and ACTH administration in girls with pubertal disturbances [Abstract in Rivista]
Predieri, Barbara; Iughetti, Lorenzo; L., Cobellis; S., Luisi; M., Luisi; S., Forese; F., Petraglia; S., Bernasconi
abstract

N.A.

2001 - Evaluation of Growth Hormone bioactivity: a useful tool for short stature diagnosis [Abstract in Rivista]
Iughetti, Lorenzo; Predieri, Barbara; S., Milioli; S., Forese; P., Travaglino; M., Bozzola; S., Bernasconi
abstract

N.A.

2001 - Ipertricosi ed irsutismo [Articolo su rivista]
Predieri, Barbara; Milioli, S; Iughetti, Lorenzo
abstract

N.A.

2001 - Rhabdomyoma of a rare type in a child: Case report and literature review [Articolo su rivista]
Cacciari, Alfredo; Predieri, Barbara; Mordenti, M; Ceccarelli, Pl; Maiorana, Antonino; Cerofolini, E; Bernasconi, S.
abstract

We describe a 9-year-old boy who presented with dyspnea and with a neck mass which was initially described as a thyroid nodule, At the end of the diagnostic-therapeutic research this mass was finally diagnosed as an adult rhabdomyoma originating from the mediastinum. This is an extremely rare tumor which is usually found in the adult population.

2001 - Sport, pubertà, adolescenza. [Articolo su rivista]
Iughetti, Lorenzo; Milioli, S; Predieri, Barbara; Stendardo, A; Bernasconi, S.
abstract

N.A.

2001 - Ultrasonographic and color doppler analysis in girls with premature adrenarche [Abstract in Rivista]
Iughetti, Lorenzo; C., Battaglia; G., Regnani; Predieri, Barbara; S., Forese; S., Bernasconi
abstract

N.A.

2001 - Uterine artery color doppler analysis in the diagnosis of female precocious puberty [Abstract in Rivista]
Iughetti, Lorenzo; C., Battaglia; G., Regnani; Predieri, Barbara; C., Flamigni; S., Venturoli; S., Forese; S., Bernasconi
abstract

N.A.

2000 - Diagnosis of central precocious puberty: endocrine assessment [Articolo su rivista]
Iughetti, Lorenzo; Predieri, Barbara; M., Ferrari; C., Gallo; L., Livio; S., Milioli; S., Forese; S., Bernasconi
abstract

The new methods which are currently available have provided substantial help in performing the differential diagnosis of CPP, especially in detecting very early modifications of gonadotropin secretion. Nocturnal sampling is not a practical tool and generates discomfort for patients, and daytime samples do not yet have sufficient sensitivity; thus, determination of LH levels after GnRH stimulation is the most important test. We emphasize that the use of the GnRH agonist test improves the discrimination of the endocrine investigation, making it easier to differentiate CPP from other conditions, such necessary, but its use in isolation is not as thelarche, Determination of sex steroids is recommended.

2000 - Ipertricosi e irsutismo. [Articolo su rivista]
Bernasconi, S; Iughetti, Lorenzo; Ferrari, M; Predieri, Barbara; Ghizzoni, L; Forese, S.
abstract

N.A.

2000 - Obesità genetiche [Articolo su rivista]
Iughetti, Lorenzo; Ferrari, M; Predieri, Barbara
abstract

N.A.

1999 - Genetics and molecular biology of the GHRH-GH-IGF1 axis. [Articolo su rivista]
Bernasconi, S; Bergomi, A; Milioli, S; Tirendi, A; Mastronardi, G; Mariani, S; Predieri, Barbara; Ferrari, M; Geti, M; Livio, L; Rossi, K; Forese, S; Iughetti, Lorenzo
abstract

In this paper, the genetics and molecular biology of the GHRH-GH-IGF-I (Growth Hormone Releasing hormone-Growth Hormone-Insulin like Growth Factor I) axis involved in the pathogenesis of short stature are reviewed. Short stature associated with GH deficiency is estimated to occur in about 1/4000-10,000 live births; 3-30% of cases affect first-degree relatives, suggesting a genetic aetiology. Identification of such molecular defects is very recent and dependent on new findings on the physiology of GHRH-GH-IGF-I axis: for example the pituitary-specific transcription factors and their mutations have only been described in the last few years. The epidemiological importance of the identified molecular defect depends on the level of the axis involved, but the prevalence of some of these genetic defects is probably underestimated. Time will tell what the practical relevance of these findings is and what the clinical features of the new mutations are; we will probably learn something more about the GHRH-GH-IGF-I axis: to date, no mutations have been reported regarding the GHRH gene or the IGF-I receptor.

1999 - Hemorrhagic ascites in a child with Henoch-Schönlein purpura [Articolo su rivista]
Venuta, A; Bertolani, P; Garetti, E; Venturelli, C; Predieri, B; Muttini, E D; Compagni, E
abstract

na

1996 - Immunoglobulins and convulsions [Articolo su rivista]
Cavazzuti, Gb; Guerra, A; Leoni, S; Predieri, Barbara
abstract

Fin dagli anni '70 è stato ipotizzato un coinvolgimento del sistema immunitario nella patogenesi dei processi epilettici. Anche se gli approcci al problema sono stati sinora eterogenei ed insufficienti ad elaborare una convincente ipotesi neuroimmunologica unitaria della epilettogenesi, nondimeno risultano acquisiti molti interessanti dati, come l'esistenza di auto-anticorpi circolanti per il SNC, il collegamento dell'HLA con alcune sindromi epilettiche, l'interessamento delle citochine, le alterazioni delle immunoglobuline (Ig) e l'efficacia terapeutica della loro somministrazione in pazienti epilettici.