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Marco BERTOLOTTI
Professore Ordinario
Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze sede ex-Medicina, Endocrinologia, Metabolismo e Geriatria
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Pubblicazioni
2024
- The body of evidence of late-life depression: the complex relationship between depressive symptoms, movement, dyspnea and cognition
[Articolo su rivista]
Belvederi Murri, M.; Triolo, F.; Coni, A.; Nerozzi, E.; Maietta Latessa, P.; Fantozzi, S.; Padula, N.; Escelsior, A.; Assirelli, B.; Ermini, G.; Bagnoli, L.; Zocchi, D.; Cabassi, A.; Tedeschi, S.; Toni, G.; Chattat, R.; Tripi, F.; Neviani, F.; Bertolotti, M.; Cremonini, A.; Bertakis, K. D.; Amore, M.; Chiari, L.; Zanetidou, S.
abstract
Background: Physical symptoms play an important role in late-life depression and may contribute to residual symptomatology after antidepressant treatment. In this exploratory study, we examined the role of specific bodily dimensions including movement, respiratory functions, fear of falling, cognition, and physical weakness in older people with depression.Methods: Clinically stable older patients with major depression within a Psychiatric Consultation-Liaison program for Primary Care underwent comprehensive assessment of depressive symptoms, instrumental movement analysis, dyspnea, weakness, activity limitations, cognitive function, and fear of falling. Network analysis was performed to explore the unique adjusted associations between clinical dimensions.Results: Sadness was associated with worse turning and walking ability and movement transitions from walking to sitting, as well as with worse general cognitive abilities. Sadness was also connected with dyspnea, while neurovegetative depressive burden was connected with activity limitations.Discussion: Limitations of motor and cognitive function, dyspnea, and weakness may contribute to the persistence of residual symptoms of late-life depression.
2023
- Antihypertensive treatment changes and related clinical outcomes in older hospitalized patients
[Articolo su rivista]
Cicco, S.; D'Abbondanza, M.; Proietti, M.; Zaccone, V.; Pes, C.; Caradio, F.; Mattioli, M.; Piano, S.; Marra, A. M.; Nobili, A.; Mannucci, P. M.; Pietrangelo, A.; Sesti, G.; Buzzetti, E.; Salzano, A.; Cimellaro, A.; Mannucci, P. M.; Nobili, A.; Sesti, G.; Pietrangelo, A.; Perticone, F.; Violi, F.; Corazza, G. R.; Corrao, S.; Marengoni, A.; Salerno, F.; Cesari, M.; Tettamanti, M.; Pasina, L.; Franchi, C.; Franchi, C.; Novella, A.; Tettamanti, M.; Miglio, G.; Tettamanti, M.; Galbussera, A. A.; Ardoino, I.; Novella, A.; Prisco, D.; Silvestri, E.; Emmi, G.; Bettiol, A.; Mattioli, I.; Biolo, G.; Zanetti, M.; Bartelloni, G.; Zaccari, M.; Chiuch, M.; Vanoli, M.; Grignani, G.; Pulixi, E. A.; Pirro, M.; Lupattelli, G.; Bianconi, V.; Alcidi, R.; Giotta, A.; Mannarino, M. R.; Girelli, D.; Busti, F.; Marchi, G.; Barbagallo, M.; Dominguez, L.; Beneduce, V.; Cacioppo, F.; Corrao, S.; Natoli, G.; Mularo, S.; Raspanti, M.; Argano, C.; Cavallaro, F.; Zoli, M.; Matacena, M. L.; Orio, G.; Magnolfi, E.; Serafini, G.; Simili, A.; Brunori, M.; Lazzari, I.; Simili, A.; Cappellini, M. D.; Fabio, G.; De Amicis, M. M.; De Luca, G.; Scaramellini, N.; Di Stefano, V.; Leoni, S.; Seghezzi, S.; Di Mauro, A. D.; Maira, D.; Mancarella, M.; Lucchi, T.; Rossi, P. D.; Clerici, M.; Leoni, S.; Di Mauro, A. D.; Bonini, G.; Conti, F.; Prolo, S.; Fabrizi, M.; Martelengo, M.; Vigani, G.; Di Sabatino, A.; Miceli, E.; Lenti, M. V.; Pisati, M.; Pitotti, L.; Padula, D.; Antoci, V.; Cambie, G.; Pontremoli, R.; Beccati, V.; Nobili, G.; Leoncini, G.; Alberto, J.; Cattaneo, F.; Anastasio, L.; Sofia, L.; Carbone, M.; Cipollone, F.; Guagnano, M. T.; Rossi, I.; Valeriani, E.; D'Ardes, D.; Esposito, L.; Sestili, S.; Angelucci, E.; Mancuso, G.; Calipari, D.; Bartone, M.; Delitala, G.; Berria, M.; Delitala, A.; Muscaritoli, M.; Molfino, A.; Petrillo, E.; Giorgi, A.; Gracin, C.; Imbimbo, G.; Zuccala, G.; D'Aurizio, G.; Romanelli, G.; Marengoni, A.; Volpini, A.; Lucente, D.; Manzoni, F.; Pirozzi, A.; Zucchelli, A.; Picardi, A.; Gentilucci, U. V.; Gallo, P.; Dell'Unto, C.; Bellelli, G.; Corsi, M.; Antonucci, C.; Sidoli, C.; Principato, G.; Bonfanti, A.; Szabo, H.; Mazzola, P.; Piazzoli, A.; Corsi, M.; Arturi, F.; Succurro, E.; Tassone, B.; Giofre, F.; Serra, M. G.; Bleve, M. A.; Brucato, A.; De Falco, T.; Negro, E.; Brenna, M.; Trotta, L.; Squintani, G. L.; Randi, M. L.; Fabris, F.; Bertozzi, I.; Bogoni, G.; Rabuini, M. V.; Prandini, T.; Ratti, F.; Zurlo, C.; Cerruti, L.; Cosi, E.; Manfredini, R.; Fabbian, F.; Boari, B.; De Giorgi, A.; Tiseo, R.; Paolisso, G.; Rizzo, M. R.; Catalano, C.; Di Meo, I.; Borghi, C.; Strocchi, E.; Ianniello, E.; Soldati, M.; Schiavone, S.; Bragagni, A.; Leoni, F. G.; De Sando, V.; Scarduelli, S.; Cammarosano, M.; Pareo, I.; Sabba, C.; Vella, F. S.; Suppressa, P.; De Vincenzo, G. M.; Comitangelo, A.; Amoruso, E.; Custodero, C.; Re, G.; Schilardi, A.; Loparco, F.; Fenoglio, L.; Falcetta, A.; Giraudo, A. V.; D'Aniano, S.; Fracanzani, A. L.; Tiraboschi, S.; Cespiati, A.; Oberti, G.; Sigon, G.; Cinque, F.; Peyvandi, F.; Rossio, R.; Colombo, G.; Agosti, P.; Pagliaro, E.; Semproni, E.; Ciro, C.; Monzani, V.; Savojardo, V.; Ceriani, G.; Folli, C.; Salerno, F.; Pallini, G.; Montecucco, F.; Ottonello, L.; Caserza, L.; Vischi, G.; Kassem, S.; Liberale, L.; Liberato, N. L.; Tognin, T.; Purrello, F.; Di Pino, A.; Piro, S.; Rozzini, R.; Falanga, L.; Pisciotta, M. S.; Bellucci, F. B.; Buffelli, S.; Ferrandina, C.; Mazzeo, F.; Spazzini, E.; Cono, G.; Cesaroni, G.; Montrucchio, G.; Peasso, P.; Favale, E.; Poletto, C.; Margaria, C.; Sanino, M.; Violi, F.; Perri, L.; Guasti, L.; Rotunno, F.; Castiglioni, L.; Maresca, A.; Squizzato, A.; Campiotti, L.; Grossi, A.; Diprizio, R. D.; Dentali, F.; Bertolotti, M.; Mussi, C.; Lancellotti, G.; Libbra, M. V.; Galassi, M.; Grassi, Y.; Greco, A.; Bigi, E.; Pellegrini, E.; Orlandi, L.; Dondi, G.; Carulli, L.; Sciacqua, A.; Perticone, M.; Battaglia, R.; Maio, R.; Scozzafava, A.; Condoleo, V.; Falbo, T.; Colangelo, L.; Filice, M.; Clausi, E
abstract
Background: Hypertension management in older patients represents a challenge, particularly when hospitalized. Objective: The objective of this study is to investigate the determinants and related outcomes of antihypertensive drug prescription in a cohort of older hospitalized patients. Methods: A total of 5671 patients from REPOSI (a prospective multicentre observational register of older Italian in-patients from internal medicine or geriatric wards) were considered; 4377 (77.2%) were hypertensive. Minimum treatment (MT) for hypertension was defined according to the 2018 ESC guidelines [an angiotensin-converting-enzyme-inhibitor (ACE-I) or an angiotensin-receptor-blocker (ARB) with a calcium-channel-blocker (CCB) and/or a thiazide diuretic; if >80 years old, an ACE-I or ARB or CCB or thiazide diuretic]. Determinants of MT discontinuation at discharge were assessed. Study outcomes were any cause rehospitalization/all cause death, all-cause death, cardiovascular (CV) hospitalization/death, CV death, non-CV death, evaluated according to the presence of MT at discharge. Results: Hypertensive patients were older than normotensives, with a more impaired functional status, higher burden of comorbidity and polypharmacy. A total of 2233 patients were on MT at admission, 1766 were on MT at discharge. Discontinuation of MT was associated with the presence of comorbidities (lower odds for diabetes, higher odds for chronic kidney disease and dementia). An adjusted multivariable logistic regression analysis showed that MT for hypertension at discharge was associated with lower risk of all-cause death, all-cause death/hospitalization, CV death, CV death/hospitalization and non-CV death. Conclusions: Guidelines-suggested MT for hypertension at discharge is associated with a lower risk of adverse clinical outcomes. Nevertheless, changes in antihypertensive treatment still occur in a significant proportion of older hospitalized patients.
2023
- Changes in cholesterol homeostasis associated with aging and with age-related conditions: pathophysiological and clinical implications
[Articolo su rivista]
Bertolotti, M.; Lancellotti, G.; Mussi, C.
abstract
2022
- Efficacy of a multiple-component and multifactorial personalized fall prevention program in a mixed population of community-dwelling older adults with stroke, Parkinson's Disease, or frailty compared to usual care: The PRE.C.I.S.A. randomized controlled trial
[Articolo su rivista]
LA PORTA, Fabio; Lullini, Giada; Caselli, Serena; Valzania, Franco; Mussi, Chiara; Tedeschi, Claudio; Pioli, Giulio; Bondavalli, Massimo; Bertolotti, Marco; Banchelli, Federico; D'Amico, Roberto; Vicini, Roberto; Puglisi, Silvia; Clerici, Pierina Viviana; Chiari, Lorenzo; and PRECISA Group members, ; LA PORTA, Fabio; Caselli, Serena; Clerici, Pierina Viviana; Cavazza, Stefano; Serraglio, Valeria; Vannini Maria Cristina, ; Bovolenta, Federica; Lullini, Giada; Puglisi, Silvia; Gallo, Angela; Mussi, Chiara; Bertolotti, Marco; Scotto, Roberto; Lancellotti, Giulia; Franco, Valzania; Francesca, Falzone; Monica, Montanari; Maria Luisa De Luca, ; Malagoli, Emanuela; Elisa, Franchini; Luisa, Palmisano; Franca, Serafini; Tedeschi, Claudio; Gioacchino, Anselmi; Valentina, D’Alleva; Mariangela Di Matteo, ; Rosalinda, Ferrari; Costi, Stefania; Filomena, Simeone; Giulia, D’Apote; Alessandra, Rizzica; Galavotti, Maria Beatrice; Marta, Ghirelli; Giulio, Pioli; Bendini, Chiara; Lancellotti, Giulia; Massimo, Bondavalli; Eleni, Georgopoulos; D'Amico, Roberto; Balduzzi, Sara; Vicini, Roberto; Banchelli, Federico; Lorenzo, Chiari; Sabato, Mellone; Alice, Coni
abstract
Fall risk in the elderly is a major public health issue due to the injury-related consequences and the risk of associated long-term disability. However, delivering preventive interventions in usual clinical practice still represents a challenge.
2022
- MoCA 7.1: Multicenter Validation of the First Italian Version of Montreal Cognitive Assessment
[Articolo su rivista]
Pirani, A.; Nasreddine, Z.; Neviani, F.; Fabbo, A.; Rocchi, M. B.; Bertolotti, M.; Tulipani, C.; Galassi, M.; Belvederi Murri, M.; Neri, M.
abstract
2022
- Predicting hospital readmissions in older patients with heart failure with advanced bioinformatics tools: focus on the role of vulnerability and frailty
[Articolo su rivista]
Bertolotti, Marco; Franchi, Carlotta; Lancellotti, Giulia; Mandelli, Sara; Mussi, Chiara
abstract
2022
- Updated Recommendations on Cardiovascular Prevention in 2022: An Executive Document of the Italian Society of Cardiovascular Prevention
[Capitolo/Saggio]
Volpe, M.; Gallo, G.; Modena, M. G.; Ferri, C.; Desideri, G.; Tocci, G.; Bellone, S.; Bertolotti, M.; Biffi, A.; Consoli, A.; Corsini, A.; Nati, G.; Pirro, M.; Rubattu, S.; Trimarco, B.; de Kreutzenberg, S. V.; Volpe, R.
abstract
This executive document reflects and updates the key points of a Consensus document on Cardiovascular (CV) Prevention realized through the contribution of a number of Italian Scientific Societies and coordinated by the Italian Society of Cardiovascular Prevention (SIPREC). The aim of this executive document is to analyze and discuss the new recommendations introduced by international guidelines for the management of major CV risk factors, such as hypertension, dyslipidemias and type 2 diabetes, consisting in the identification of lower therapeutic targets, in the promotion of combination fixed drug therapies and in the introduction in routine clinical practice of new effective pharmacological classes. Moreover, the document highlights the importance of effective CV prevention strategies during the the coronavirus disease 2019 (COVID-19) outbreak which has dramatically changed the priorities and the use of available resources by the national healthcare systems and have caused a reduction of programmed follow-up visits and procedures and even of hospital admissions for severe acute pathologies. In addition, the pandemic and the consequent lockdown measures imposed have caused a widespread diffusion of unhealthy behaviors with detrimental effects on the CV system. In such a context, reinforcement of CV prevention activities may play a key role in reducing the future impact of these deleterious conditions.
2021
- Hyperglycemia at admission, comorbidities, and in-hospital mortality in elderly patients hospitalized in internal medicine wards: data from the RePoSI Registry
[Articolo su rivista]
Corrao, S.; Nobili, A.; Natoli, G.; Mannucci, P. M.; Perticone, F.; Pietrangelo, A.; Argano, C.; Licata, G.; Violi, F.; Corazza, G. R.; Corrao, S.; Marengoni, A.; Salerno, F.; Cesari, M.; Tettamanti, M.; Pasina, L.; Franchi, C.; Franchi, C.; Cortesi, L.; Tettamanti, M.; Miglio, G.; Tettamanti, M.; Cortesi, L.; Ardoino, I.; Novella, A.; Prisco, D.; Silvestri, E.; Emmi, G.; Bettiol, A.; Caterina, C.; Biolo, G.; Zanetti, M.; Guadagni, M.; Zaccari, M.; Chiuch, M.; Zaccari, M.; Vanoli, M.; Grignani, G.; Pulixi, E. A.; Bernardi, M.; Bassi, S. L.; Santi, L.; Zaccherini, G.; Lupattelli, G.; Mannarino, E.; Bianconi, V.; Paciullo, F.; Alcidi, R.; Nuti, R.; Valenti, R.; Ruvio, M.; Cappelli, S.; Palazzuoli, A.; Girelli, D.; Busti, F.; Marchi, G.; Barbagallo, M.; Dominguez, L.; Cocita, F.; Beneduce, V.; Plances, L.; Mularo, S.; Raspanti, M.; Zoli, M.; Lazzari, I.; Brunori, M.; Fabbri, E.; Magalotti, D.; Arno, R.; Pasini, F. L.; Capecchi, P. L.; Palasciano, G.; Modeo, M. E.; Di Gennaro, C.; Cappellini, M. D.; Maira, D.; Di Stefano, V.; Fabio, G.; Seghezzi, S.; Mancarella, M.; De Amicis, M. M.; De Luca, G.; Scaramellini, N.; Cesari, M.; Rossi, P. D.; Damanti, S.; Clerici, M.; Conti, F.; Bonini, G.; Ottolini, B. B.; Di Sabatino, A.; Miceli, E.; Lenti, M. V.; Pisati, M.; Dominioni, C. C.; Murialdo, G.; Marra, A.; Cattaneo, F.; Pontremoli, R.; Beccati, V.; Nobili, G.; Secchi, M. B.; Ghelfi, D.; Anastasio, L.; Sofia, L.; Carbone, M.; Cipollone, F.; Guagnano, M. T.; Valeriani, E.; Rossi, I.; Mancuso, G.; Calipari, D.; Bartone, M.; Delitala, G.; Berria, M.; Pes, C.; Delitala, A.; Muscaritoli, M.; Molfino, A.; Petrillo, E.; Zuccala, G.; D'Aurizio, G.; Romanelli, G.; Marengoni, A.; Zucchelli, A.; Manzoni, F.; Volpini, A.; Picardi, A.; Gentilucci, U. V.; Gallo, P.; Dell'Unto, C.; Annoni, G.; Corsi, M.; Bellelli, G.; Zazzetta, S.; Mazzola, P.; Szabo, H.; Bonfanti, A.; Arturi, F.; Succurro, E.; Rubino, M.; Tassone, B.; Sesti, G.; Serra, M. G.; Bleve, M. A.; Gasbarrone, L.; Sajeva, M. R.; Brucato, A.; Ghidoni, S.; Fabris, F.; Bertozzi, I.; Bogoni, G.; Rabuini, M. V.; Cosi, E.; Scarinzi, P.; Amabile, A.; Omenetto, E.; Prandini, T.; Manfredini, R.; Fabbian, F.; Boari, B.; De Giorgi, A.; Tiseo, R.; De Giorgio, R.; Paolisso, G.; Rizzo, M. R.; Borghi, C.; Strocchi, E.; Ianniello, E.; Soldati, M.; Sabba, C.; Vella, F. S.; Suppressa, P.; Schilardi, A.; Loparco, F.; De Vincenzo, G. M.; Comitangelo, A.; Amoruso, E.; Fenoglio, L.; Falcetta, A.; Bracco, C.; Fargion, A. L. F. S.; Tiraboschi, S.; Cespiati, A.; Oberti, G.; Sigon, G.; Peyvandi, F.; Rossio, R.; Ferrari, B.; Colombo, G.; Agosti, P.; Monzani, V.; Savojardo, V.; Folli, C.; Ceriani, G.; Salerno, F.; Pallini, G.; Dallegri, F.; Ottonello, L.; Liberale, L.; Caserza, L.; Salam, K.; Liberato, N. L.; Tognin, T.; Bianchi, G. B.; Giaquinto, S.; Purrello, F.; Di Pino, A.; Piro, S.; Rozzini, R.; Falanga, L.; Spazzini, E.; Ferrandina, C.; Montrucchio, G.; Petitti, P.; Peasso, P.; Favale, E.; Poletto, C.; Salmi, R.; Gaudenzi, P.; Violi, F.; Perri, L.; Landolfi, R.; Montalto, M.; Mirijello, A.; Guasti, L.; Castiglioni, L.; Maresca, A.; Squizzato, A.; Campiotti, L.; Grossi, A.; Bertolotti, M.; Mussi, C.; Lancellotti, G.; Libbra, M. V.; Dondi, G.; Pellegrini, E.; Carulli, L.; Galassi, M.; Grassi, Y.; Perticone, M.; Battaglia, R.; Filice, M.; Maio, R.; Stanghellini, V.; Ruggeri, E.; del Vecchio, S.; Salvi, A.; Leonardi, R.; Damiani, G.; Capeci, W.; Gabrielli, A.; Mattioli, M.; Martino, G. P.; Biondi, L.; Pettinari, P.; Ghio, R.; Col, A. D.; Minisola, S.; Colangelo, L.; Cilli, M.; Labbadia, G.; Afeltra, A.; Marigliano, B.; Pipita, M. E.; Castellino, P.; Zanoli, L.; Pignataro, S.; Gennaro, A.; Blanco, J.; Saracco, V.; Fogliati, M.; Bussolino, C.; Mete, F.; Gino, M.; Cittadini, A.; Vigorito, C.; Arcopinto, M.; Salzano, A.; Bobbio, E.; Marra, A. M.; Sirico, D.; Moreo, G.; Gasparini, F.; Prolo, S.; Pina, G.; Ballestrero, A.; Ferrando, F.; Berra, S.; Dassi, S.; Nava, M. C.; Graziella, B.; Baldassarre, S.; Fragapani, S.; Gruden,
abstract
Aims: The association between hyperglycemia at hospital admission and relevant short- and long-term outcomes in elderly population is known. We assessed the effects on mortality of hyperglycemia, disability, and multimorbidity at admission in internal medicine ward in patients aged ≥ 65 years. Methods: Data were collected from an active register of 102 internal medicine and geriatric wards in Italy (RePoSi project). Patients were recruited during four index weeks of a year. Socio-demographic data, reason for hospitalization, diagnoses, treatment, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), renal function, functional (Barthel Index), and cognitive status (Short Blessed Test) and mood disorders (Geriatric Depression Scale) were recorded. Mortality rates were assessed in hospital 3 and 12 months after discharge. Results: Of the 4714 elderly patients hospitalized, 361 had a glycemia level ≥ 250 mg/dL at admission. Compared to subjects with lower glycemia level, patients with glycemia ≥ 250 mg/dL showed higher rates of male sex, smoke and class III obesity. These patients had a significantly lower Barthel Index (p = 0.0249), higher CIRS-SI and CIRS-CI scores (p = 0.0025 and p = 0.0013, respectively), and took more drugs. In-hospital mortality rate was 9.2% and 5.1% in subjects with glycemia ≥ 250 and < 250 mg/dL, respectively (p = 0.0010). Regression analysis showed a strong association between in-hospital death and glycemia ≥ 250 mg/dL (OR 2.07; [95% CI 1.34–3.19]), Barthel Index ≤ 40 (3.28[2.44–4.42]), CIRS-SI (1.87[1.27–2.77]), and male sex (1.54[1.16–2.03]). Conclusions: The stronger predictors of in-hospital mortality for older patients admitted in general wards were glycemia level ≥ 250 mg/dL, Barthel Index ≤ 40, CIRS-SI, and male sex.
2021
- Interactions of oxysterols with atherosclerosis biomarkers in subjects with moderate hypercholesterolemia and effects of a nutraceutical combination (Bifidobacterium longum BB536, red yeast rice extract) (randomized, double-blind, placebo-controlled study)
[Articolo su rivista]
Cicolari, S.; Pavanello, C.; Olmastroni, E.; Puppo, M. D.; Bertolotti, M.; Mombelli, G.; Catapano, A. L.; Calabresi, L.; Magni, P.
abstract
Background: Oxysterol relationship with cardiovascular (CV) risk factors is poorly explored, especially in moderately hypercholesterolaemic subjects. Moreover, the impact of nutraceuticals controlling hypercholesterolaemia on plasma levels of 24-, 25-and 27-hydroxycholesterol (24-OHC, 25-OHC, 27-OHC) is unknown. Methods: Subjects (n = 33; 18–70 years) with moderate hypercholesterolaemia (low-density lipoprotein cholesterol (LDL-C:): 130–200 mg/dL), in primary CV prevention as well as low CV risk were studied cross-sectionally. Moreover, they were evaluated after treatment with a nutraceutical combination (Bifidobacterium longum BB536, red yeast rice extract (10 mg/dose monacolin K)), following a double-blind, randomized, placebo-controlled design. We evaluated 24-OHC, 25-OHC and 27-OHC levels by gas chromatography/mass spectrometry analysis. Results: 24-OHC and 25-OHC were significantly correlated, 24-OHC was correlated with apoB. 27-OHC and 27-OHC/total cholesterol (TC) were higher in men (median 209 ng/mL and 77 ng/mg, respectively) vs. women (median 168 ng/mL and 56 ng/mg, respectively); 27-OHC/TC was significantly correlated with abdominal circumference, visceral fat and, negatively, with high-density lipoprotein cholesterol (HDL-C). Triglycerides were significantly correlated with 24-OHC, 25-OHC and 27-OHC and with 24-OHC/TC and 25-OHC/TC. After intervention, 27-OHC levels were significantly reduced by 10.4% in the nutraceutical group Levels of 24-OHC, 24-OHC/TC, 25-OHC, 25-OHC/TC and 27-OHC/TC were unchanged. Conclusions: In this study, conducted in moderate hypercholesterolemic subjects, we observed novel relationships between 24-OHC, 25-OHC and 27-OHC and CV risk biomarkers. In addition, no adverse changes of OHC levels upon nutraceutical treatment were found.
2021
- Pattern of comorbidities and 1-year mortality in elderly patients with COPD hospitalized in internal medicine wards: data from the RePoSI Registry
[Articolo su rivista]
Argano, C.; Scichilone, N.; Natoli, G.; Nobili, A.; Corazza, G. R.; Mannucci, P. M.; Perticone, F.; Corrao, S.; Pietrangelo, A.; Licata, G.; Violi, F.; Corrao, S.; Marengoni, A.; Salerno, F.; Cesari, M.; Tettamanti, M.; Pasina, L.; Franchi, C.; Miglio, G.; Cortesi, L.; Ardoino, I.; Novella, A.; Prisco, D.; Silvestri, E.; Emmi, G.; Bettiol, A.; Caterina, C.; Biolo, G.; Zanetti, M.; Guadagni, M.; Zaccari, M.; Chiuch, M.; Zaccari, M.; Vanoli, M.; Grignani, G.; Pulixi, E. A.; Bernardi, M.; Bassi, S. L.; Santi, L.; Zaccherini, G.; Lupattelli, G.; Mannarino, E.; Bianconi, V.; Paciullo, F.; Alcidi, R.; Nuti, R.; Valenti, R.; Ruvio, M.; Cappelli, S.; Palazzuoli, A.; Girelli, D.; Busti, F.; Marchi, G.; Barbagallo, M.; Dominguez, L.; Cocita, F.; Beneduce, V.; Plances, L.; Corrao, S.; Mularo, S.; Raspanti, M.; Cavallaro, F.; Zoli, M.; Lazzari, I.; Brunori, M.; Fabbri, E.; Magalotti, D.; Arno, R.; Pasini, F. L.; Capecchi, P. L.; Palasciano, G.; Modeo, M. E.; Di Gennaro, C.; Cappellini, M. D.; Maira, D.; Di Stefano, V.; Fabio, G.; Seghezzi, S.; Mancarella, M.; De Amicis, M. M.; De Luca, G.; Scaramellini, N.; Cesari, M.; Rossi, P. D.; Damanti, S.; Clerici, M.; Conti, F.; Bonini, G.; Ottolini, B. B.; Di Sabatino, A.; Miceli, E.; Lenti, M. V.; Pisati, M.; Dominioni, C. C.; Murialdo, G.; Marra, A.; Cattaneo, F.; Pontremoli, R.; Beccati, V.; Nobili, G.; Secchi, M. B.; Ghelfi, D.; Anastasio, L.; Sofia, L.; Carbone, M.; Cipollone, F.; Guagnano, M. T.; Valeriani, E.; Rossi, I.; Mancuso, G.; Calipari, D.; Bartone, M.; Delitala, G.; Berria, M.; Pes, C.; Delitala, A.; Muscaritoli, M.; Molfino, A.; Petrillo, E.; Zuccala, G.; D'Aurizio, G.; Romanelli, G.; Zucchelli, A.; Manzoni, F.; Volpini, A.; Picardi, A.; Gentilucci, U. V.; Gallo, P.; Dell'Unto, C.; Annoni, G.; Corsi, M.; Bellelli, G.; Zazzetta, S.; Mazzola, P.; Szabo, H.; Bonfanti, A.; Arturi, F.; Succurro, E.; Rubino, M.; Tassone, B.; Sesti, G.; Serra, M. G.; Bleve, M. A.; Gasbarrone, L.; Sajeva, M. R.; Brucato, A.; Ghidoni, S.; Fabris, F.; Bertozzi, I.; Bogoni, G.; Rabuini, M. V.; Cosi, E.; Scarinzi, P.; Amabile, A.; Omenetto, E.; Prandini, T.; Manfredini, R.; Fabbian, F.; Boari, B.; De Giorgi, A.; Tiseo, R.; De Giorgio, R.; Paolisso, G.; Rizzo, M. R.; Borghi, C.; Strocchi, E.; Ianniello, E.; Soldati, M.; Sabba, C.; Vella, F. S.; Suppressa, P.; Schilardi, A.; Loparco, F.; De Vincenzo, G. M.; Comitangelo, A.; Amoruso, E.; Fenoglio, L.; Falcetta, A.; Bracco, C.; Fracanzani Silvia Fargion, A. L.; Tiraboschi, S.; Cespiati, A.; Oberti, G.; Sigon, G.; Peyvandi, F.; Rossio, R.; Ferrari, B.; Colombo, G.; Agosti, P.; Monzani, V.; Savojardo, V.; Folli, C.; Ceriani, G.; Salerno, F.; Pallini, G.; Dallegri, F.; Ottonello, L.; Liberale, L.; Caserza, L.; Salam, K.; Liberato, N. L.; Tognin, T.; Bianchi, G. B.; Giaquinto, S.; Purrello, F.; Di Pino, A.; Piro, S.; Rozzini, R.; Falanga, L.; Spazzini, E.; Ferrandina, C.; Montrucchio, G.; Petitti, P.; Peasso, P.; Favale, E.; Poletto, C.; Salmi, R.; Gaudenzi, P.; Violi, F.; Perri, L.; Landolfi, R.; Montalto, M.; Mirijello, A.; Guasti, L.; Castiglioni, L.; Maresca, A.; Squizzato, A.; Campiotti, L.; Grossi, A.; Bertolotti, M.; Mussi, C.; Lancellotti, G.; Libbra, M. V.; Dondi, G.; Pellegrini, E.; Carulli, L.; Galassi, M.; Grassi, Y.; Perticone, M.; Battaglia, R.; Filice, M.; Maio, R.; Stanghellini, V.; Ruggeri, E.; del Vecchio, S.; Salvi, A.; Leonardi, R.; Damiani, G.; Capeci, W.; Gabrielli, A.; Mattioli, M.; Martino, G. P.; Biondi, L.; Pettinari, P.; Ghio, R.; Col, A. D.; Minisola, S.; Colangelo, L.; Cilli, M.; Labbadia, G.; Afeltra, A.; Marigliano, B.; Pipita, M. E.; Castellino, P.; Zanoli, L.; Pignataro, S.; Gennaro, A.; Blanco, J.; Saracco, V.; Fogliati, M.; Bussolino, C.; Mete, F.; Gino, M.; Cittadini, A.; Vigorito, C.; Arcopinto, M.; Salzano, A.; Bobbio, E.; Marra, A. M.; Sirico, D.; Moreo, G.; Gasparini, F.; Prolo, S.; Pina, G.; Ballestrero, A.; Ferrando, F.; Berra, S.; Dassi, S.; Nava, M. C.; Graziella, B.; Baldassarre, S.; Fragapani, S.; Gruden, G.; Galanti, G.;
abstract
Currently, chronic obstructive pulmonary disease (COPD) represents the fourth cause of death worldwide with significant economic burden. Comorbidities increase in number and severity with age and are identified as important determinants that influence the prognosis. In this observational study, we retrospectively analyzed data collected from the RePoSI register. We aimed to investigate comorbidities and outcomes in a cohort of hospitalized elderly patients with the clinical diagnosis of COPD. Socio-demographic, clinical characteristics and laboratory findings were considered. The association between variables and in-hospital, 3-month and 1-year follow-up were analyzed. Among 4696 in-patients, 932 (19.8%) had a diagnosis of COPD. Patients with COPD had more hospitalization, a significant overt cognitive impairment, a clinically significant disability and more depression in comparison with non-COPD subjects. COPD patients took more drugs, both at admission, in-hospital stay, discharge and 3-month and 1-year follow-up. 14 comorbidities were more frequent in COPD patients. Cerebrovascular disease was an independent predictor of in-hospital mortality. At 3-month follow-up, male sex and hepatic cirrhosis were independently associated with mortality. ICS-LABA therapy was predictor of mortality at in-hospital, 3-month and 1-year follow-up. This analysis showed the severity of impact of COPD and its comorbidities in the real life of internal medicine and geriatric wards.
2021
- Prevention Italy 2021 - An update of the 2018 Consensus document and recommendations for the prevention of cardiovascular disease in Italy
[Capitolo/Saggio]
Battistoni, A.; Gallo, G.; Aragona, C. O.; Barchiesi, F.; Basolo, A.; Bellone, S.; Bellotti, P.; Bertolotti, M.; Bianco, A.; Biffi, A.; Borghi, C.; Cicero, A. F. G.; Consoli, A.; Corsini, A.; Desideri, G.; Di Giacinto, B.; Fernando, F.; Ferri, C.; Galiuto, L.; Grassi, D.; Grassi, G.; Icardi, G.; Indolfi, C.; Lodi, E.; Modena, M. G.; Muiesan, M. L.; Nati, G.; Orsi, A.; Palermi, S.; Parati, G.; Passantino, A.; Patelli, A.; Pelliccia, A.; Pengo, M.; Filardi, P. P.; Perseghin, G.; Pirro, M.; Pontremoli, R.; Rengo, G.; Ricotti, R.; Rizzoni, D.; Rocca, B.; Rotella, C.; Rubattu, S.; Salvetti, G.; Sciacqua, A.; Serdoz, A.; Sirico, F.; Squeo, M. R.; Tocci, G.; Trimarco, B.; Vigili de Kreutzenberg, S.; Volpe, R.; Volpe, M.
abstract
2021
- The multifaceted spectrum of liver cirrhosis in older hospitalised patients: Analysis of the REPOSI registry
[Articolo su rivista]
De Vincentis, A.; Vespasiani-Gentilucci, U.; Costanzo, L.; Novella, A.; Cortesi, L.; Nobili, A.; Mannucci, P. M.; Incalzi, R. A.; Mannucci, P. M.; Nobili, A.; Pietrangelo, A.; Perticone, F.; Licata, G.; Violi, F.; Corazza, G. R.; Corrao, S.; Marengoni, A.; Salerno, F.; Cesari, M.; Tettamanti, M.; Pasina, L.; Franchi, C.; Franchi, C.; Cortesi, L.; Tettamanti, M.; Miglio, G.; Tettamanti, M.; Cortesi, L.; Ardoino, I.; Novella, A.; Prisco, D.; Silvestri, E.; Emmi, G.; Bettiol, A.; Mattioli, I.; Biolo, G.; Zanetti, M.; Bartelloni, G.; Vanoli, M.; Grignani, G.; Pulixi, E. A.; Lupattelli, G.; Bianconi, V.; Alcidi, R.; Girelli, D.; Busti, F.; Marchi, G.; Barbagallo, M.; Dominguez, L.; Beneduce, V.; Cacioppo, F.; Corrao, S.; Natoli, G.; Mularo, S.; Raspanti, M.; Zoli, M.; Matacena, M. L.; Orio, G.; Magnolfi, E.; Serafini, G.; Simili, A.; Palasciano, G.; Modeo, M. E.; Gennaro, C. D.; Cappellini, M. D.; Fabio, G.; De Amicis, M. M.; De Luca, G.; Scaramellini, N.; Cesari, M.; Rossi, P. D.; Damanti, S.; Clerici, M.; Leoni, S.; Di Mauro, A. D.; Di Sabatino, A.; Miceli, E.; Lenti, M. V.; Pisati, M.; Dominioni, C. C.; Pontremoli, R.; Beccati, V.; Nobili, G.; Leoncini, G.; Anastasio, L.; Carbone, M.; Cipollone, F.; Guagnano, M. T.; Rossi, I.; Mancuso, G.; Calipari, D.; Bartone, M.; Delitala, G.; Berria, M.; Delitala, A.; Muscaritoli, M.; Molfino, A.; Petrillo, E.; Giorgi, A.; Gracin, C.; Zuccala, G.; D'Aurizio, G.; Romanelli, G.; Marengoni, A.; Volpini, A.; Lucente, D.; Picardi, A.; Gentilucci, U. V.; Bellelli, G.; Corsi, M.; Antonucci, C.; Sidoli, C.; Principato, G.; Arturi, F.; Succurro, E.; Tassone, B.; Giofre, F.; Serra, M. G.; Bleve, M. A.; Brucato, A.; De Falco, T.; Fabris, F.; Bertozzi, I.; Bogoni, G.; Rabuini, M. V.; Prandini, T.; Manfredini, R.; Fabbian, F.; Boari, B.; De Giorgi, A.; Tiseo, R.; Paolisso, G.; Rizzo, M. R.; Catalano, C.; Borghi, C.; Strocchi, E.; Ianniello, E.; Soldati, M.; Schiavone, S.; Bragagni, A.; Sabba, C.; Vella, F. S.; Suppressa, P.; De Vincenzo, G. M.; Comitangelo, A.; Amoruso, E.; Custodero, C.; Fenoglio, L.; Falcetta, A.; Fracanzani, A. L.; Tiraboschi, S.; Cespiati, A.; Oberti, G.; Sigon, G.; Peyvandi, F.; Rossio, R.; Colombo, G.; Agosti, P.; Monzani, V.; Savojardo, V.; Ceriani, G.; Salerno, F.; Pallini, G.; Montecucco, F.; Ottonello, L.; Caserza, L.; Vischi, G.; Liberato, N. L.; Tognin, T.; Purrello, F.; Di Pino, A.; Piro, S.; Rozzini, R.; Falanga, L.; Pisciotta, M. S.; Bellucci, F. B.; Buffelli, S.; Montrucchio, G.; Peasso, P.; Favale, E.; Poletto, C.; Margaria, C.; Sanino, M.; Violi, F.; Perri, L.; Guasti, L.; Castiglioni, L.; Maresca, A.; Squizzato, A.; Campiotti, L.; Grossi, A.; Diprizio, R. D.; Bertolotti, M.; Mussi, C.; Lancellotti, G.; Libbra, M. V.; Galassi, M.; Grassi, Y.; Greco, A.; Sciacqua, A.; Perticone, M.; Battaglia, R.; Maio, R.; Stanghellini, V.; Ruggeri, E.; Del Vecchio, S.; Salvi, A.; Leonardi, R.; Damiani, G.; Capeci, W.; Mattioli, M.; Martino, G. P.; Biondi, L.; Pettinari, P.; Ghio, R.; Col, A. D.; Minisola, S.; Colangelo, L.; Cilli, M.; Labbadia, G.; Afeltra, A.; Pipita, M. E.; Castellino, P.; Zanoli, L.; Gennaro, A.; Gaudio, A.; Saracco, V.; Fogliati, M.; Bussolino, C.; Mete, F.; Gino, M.; Vigorito, C.; Cittadini, A.; Moreo, G.; Prolo, S.; Pina, G.; Ballestrero, A.; Ferrando, F.; Gonella, R.; Cerminara, D.; Berra, S.; Dassi, S.; Nava, M. C.; Graziella, B.; Baldassarre, S.; Fragapani, S.; Gruden, G.; Galanti, G.; Mascherini, G.; Petri, C.; Stefani, L.; Girino, M.; Piccinelli, V.; Nasso, F.; Gioffre, V.; Pasquale, M.; Sechi, L.; Catena, C.; Colussi, G.; Cavarape, A.; Da Porto, A.; Passariello, N.; Rinaldi, L.; Berti, F.; Famularo, G.; Tarsitani, P.; Castello, R.; Pasino, M.; Ceda, G. P.; Maggio, M. G.; Morganti, S.; Artoni, A.; Grossi, M.; Del Giacco, S.; Firinu, D.; Costanzo, G.; Argiolas, G.; Montalto, G.; Licata, A.; Montalto, F. A.; Corica, F.; Basile, G.; Catalano, A.; Bellone, F.; Principato, C.; Malatino, L.; Stancanelli, B.; Terranova, V.; Di Marca, S.; Di Quattro, R.; Malfa, L. L
abstract
Background: Knowledge on the main clinical and prognostic characteristics of older multimorbid subjects with liver cirrhosis (LC) admitted to acute medical wards is scarce. Objectives: To estimate the prevalence of LC among older patients admitted to acute medical wards and to assess the main clinical characteristics of LC along with its association with major clinical outcomes and to explore the possibility that well-distinguished phenotypic profiles of LC have classificatory and prognostic properties. Methods: A cohort of 6,193 older subjects hospitalised between 2010 and 2018 and included in the REPOSI registry was analysed. Results: LC was diagnosed in 315 patients (5%). LC was associated with rehospitalisation (age-sex adjusted hazard ratio, [aHR] 1.44; 95% CI, 1.10-1.88) and with mortality after discharge, independently of all confounders (multiple aHR, 2.1; 95% CI, 1.37-3.22), but not with in-hospital mortality and incident disability. Three main clinical phenotypes of LC patients were recognised: relatively fit subjects (FIT, N = 150), subjects characterised by poor social support (PSS, N = 89) and, finally, subjects with disability and multimorbidity (D&M, N = 76). PSS subjects had an increased incident disability (35% vs 13%, P < 0.05) compared to FIT. D&M patients had a higher mortality (in-hospital: 12% vs 3%/1%, P < 0.01; post-discharge: 41% vs 12%/15%, P < 0.01) and less rehospitalisation (10% vs 32%/34%, P < 0.01) compared to PSS and FIT. Conclusions: LC has a relatively low prevalence in older hospitalised subjects but, when present, accounts for worse post-discharge outcomes. Phenotypic analysis unravelled the heterogeneity of LC older population and the association of selected phenotypes with different clinical and prognostic features.
2021
- Therapeutic management of hypercholesterolemia and dyslipidemia
[Articolo su rivista]
Cicero, A. F. G.; Grassi, D.; Bertolotti, M.; Corsini, A.; Pirro, M.
abstract
2021
- Underdiagnosis and undertreatment of osteoporotic patients admitted in internal medicine wards in Italy between 2010 and 2016 (the REPOSI Register)
[Articolo su rivista]
Pepe, J.; Agosti, P.; Cipriani, C.; Tettamanti, M.; Nobili, A.; Colangelo, L.; Santori, R.; Cilli, M.; Minisola, S.; Mannucci, P. M.; Pietrangelo, A.; Perticone, F.; Violi, F.; Corazza, G. R.; Corrao, S.; Marengoni, A.; Salerno, F.; Cesari, M.; Pasina, L.; Cortesi, C. F. L.; Miglio, G.; Ardoino, I.; Novella, A.; Prisco, D.; Silvestri, E.; Emmi, G.; Bettiol, A.; Mattioli, I.; Biolo, G.; Zanetti, M.; Bartelloni, G.; Vanoli, M.; Grignani, G.; Pulixi, E. A.; Lupattelli, G.; Bianconi, V.; Alcidi, R.; Girelli, D.; Busti, F.; Marchi, G.; Barbagallo, M.; Dominguez, L.; Beneduce, V.; Cacioppo, F.; Corrao, S.; Natoli, G.; Mularo, S.; Raspanti, M.; Zoli, M.; Matacena, M. L.; Orio, G.; Magnolfi, E.; Serafini, G.; Simili, A.; Palasciano, G.; Modeo, M. E.; Di Gennaro, C.; Cappellini, M. D.; Fabio, G.; De Amicis, M. M.; De Luca, G.; Scaramellini, N.; Cesari, M.; Rossi, P. D.; Damanti, S.; Clerici, M.; Leoni, S.; Di Mauro, A. D.; Di Sabatino, A.; Miceli, E.; Lenti, M. V.; Pisati, M.; Dominioni, C. C.; Pontremoli, R.; Beccati, V.; Nobili, G.; Leoncini, G.; Anastasio, L.; Carbone, M.; Cipollone, F.; Guagnano, M. T.; Rossi, I.; Mancuso, G.; Calipari, D.; Bartone, M.; Delitala, G.; Berria, M.; Delitala, A.; Muscaritoli, M.; Molfino, A.; Petrillo, E.; Giorgi, A.; Gracin, C.; Zuccala, G.; D'Aurizio, G.; Romanelli, G.; Volpini, A.; Lucente, D.; Picardi, A.; Gentilucci, U. V.; Gallo, P.; Bellelli, G.; Corsi, M.; Antonucci, C.; Sidoli, C.; Principato, G.; Arturi, F.; Succurro, E.; Tassone, B.; Giofre, F.; Serra, M. G.; Bleve, M. A.; Brucato, A.; De Falco, T.; Fabris, F.; Bertozzi, I.; Bogoni, G.; Rabuini, M. V.; Prandini, T.; Manfredini, R.; Fabbian, F.; Boari, B.; De Giorgi, A.; Tiseo, R.; Paolisso, G.; Rizzo, M. R.; Catalano, C.; Borghi, C.; Strocchi, E.; Ianniello, E.; Soldati, M.; Schiavone, S.; Bragagni, A.; Sabba, C.; Vella, F. S.; Suppressa, P.; De Vincenzo, G. M.; Comitangelo, A.; Amoruso, E.; Custodero, C.; Fenoglio, L.; Falcetta, A.; Fracanzani, A. L.; Tiraboschi, S.; Cespiati, A.; Oberti, G.; Sigon, G.; Peyvandi, F.; Rossio, R.; Colombo, G.; Monzani, V.; Savojardo, V.; Ceriani, G.; Salerno, F.; Pallini, G.; Montecucco, F.; Ottonello, L.; Caserza, L.; Vischi, G.; Liberato, N. L.; Tognin, T.; Purrello, F.; Di Pino, A.; Piro, S.; Rozzini, R.; Falanga, L.; Pisciotta, M. S.; Bellucci, F. B.; Buffelli, S.; Montrucchio, G.; Peasso, P.; Favale, E.; Poletto, C.; Margaria, C.; Sanino, M.; Perri, L.; Guasti, L.; Castiglioni, L.; Maresca, A.; Squizzato, A.; Campiotti, L.; Grossi, A.; Diprizio, R. D.; Bertolotti, M.; Mussi, C.; Lancellotti, G.; Libbra, M. V.; Galassi, M.; Grassi, Y.; Greco, A.; Sciacqua, A.; Perticone, M.; Battaglia, R.; Maio, R.; Stanghellini, V.; Ruggeri, E.; del Vecchio, S.; Salvi, A.; Leonardi, R.; Damiani, G.; Capeci, W.; Mattioli, M.; Martino, G. P.; Biondi, L.; Pettinari, P.; Ghio, R.; Col, A. D.; Labbadia, G.; Afeltra, A.; Marigliano, B.; Pipita, M. E.; Castellino, P.; Zanoli, L.; Gennaro, A.; Gaudio, A.; Saracco, V.; Fogliati, M.; Bussolino, C.; Mete, F.; Gino, M.; Vigorito, C.; Cittadini, A.; Moreo, G.; Prolo, S.; Pina, G.; Ballestrero, A.; Ferrando, F.; Gonella, R.; Cerminara, D.; Berra, S.; Dassi, S.; Nava, M. C.; Graziella, B.; Baldassarre, S.; Fragapani, S.; Gruden, G.; Galanti, G.; Mascherini, G.; Petri, C.; Stefani, L.; Girino, M.; Piccinelli, V.; Nasso, F.; Gioffre, V.; Pasquale, M.; Sechi, L.; Catena, C.; Colussi, G.; Cavarape, A.; Da Porto, A.; Passariello, N.; Rinaldi, L.; Berti, F.; Famularo, G.; Tarsitani, P.; Castello, R.; Pasino, M.; Ceda, G. P.; Maggio, M. G.; Morganti, S.; Artoni, A.; Grossi, M.; Del Giacco, S.; Firinu, D.; Costanzo, G.; Argiolas, G.; Montalto, G.; Licata, A.; Montalto, F. A.; Corica, F.; Basile, G.; Catalano, A.; Bellone, F.; Principato, C.; Malatino, L.; Stancanelli, B.; Terranova, V.; Di Marca, S.; Di Quattro, R.; La Malfa, L.; Caruso, R.; Mecocci, P.; Ruggiero, C.; Boccardi, V.; Meschi, T.; Ticinesi, A.; Nouvenne, A.; Minuz, P.; Fondrieschi, L.; Imperiale, G. N.; Pirisi, M.; Fra, G. P.; Sol
abstract
Purpose: To evaluate clinical features, treatments, and outcomes of osteoporotic patients admitted to internal medicine and geriatric wards compared with non-osteoporotic patients (REPOSI registry). Methods: We studied 4714 patients hospitalized between 2010 and 2016. We reported age, sex, educational level, living status, comorbidities and drugs taken, Cumulative Illness Rating Scale (CIRS), Barthel Index, Short-Blessed Test, 4-item Geriatric Depression Scale, serum hemoglobin, creatinine, and clinical outcomes. Osteoporosis was defined based on the diagnoses recorded at admission, according to the following ICD9: 733, 805–813, 820–823. Results: Twelve percent of the patients had a preadmission diagnosis of osteoporosis. Only 20% of these had been prescribed oral bisphosphonates; 34% were taking vitamin D supplements. Osteoporotic patients were significantly older, with lower BMI, higher CIRS, and taking more drugs. They were significantly more depressed, less independent, with a higher severity of cognitive impairment compared with non-osteoporotic patients. At discharge, the number of patients receiving treatment for osteoporosis did not change. Length of stay and inhospital mortality did not differ between groups. Osteoporotic patients were more frequently nonhome discharged compared with those without osteoporosis (14.8 vs. 7.9%, p = 0.0007), mostly discharged to physical therapy or rehabilitation (8.8 vs. 2.5% of patients, p < 0.0001). Among osteoporotic patients deceased 3 months after discharge, the number of those treated with vitamin D, with or without calcium supplements, was significantly lower compared with survivors (12 vs. 32%, p = 0.0168). Conclusions: The diagnosis of osteoporosis is poorly considered both during hospital stay and at discharge; osteoporotic patients are frailer compared to non-osteoporotic patients.
2021
- Use of lipid-lowering drugs and associated outcomes according to health state profiles in hospitalized older patients
[Articolo su rivista]
Franchi, C.; Lancellotti, G.; Bertolotti, M.; Di Salvatore, S.; Nobili, A.; Mannucci, P. M.; Mussi, C.; Ardoino, I.
abstract
Objective: To assess how lipid-lowering drugs (LLDs) are administered in the hospitalized patients aged 65 and older and their association with clinical outcomes according to their health-related profiles. Design: This is a retrospective study based on data from REPOSI (REgistro POliterapie SIMI – Italian Society of Internal Medicine) register, an Italian network of internal medicine hospital wards. Setting and Participants: A total of 4642 patients with a mean age of 79 years enrolled between 2010 and 2018. Methods: Socio-demographic characteristics, functional abilities, cognitive skills, labora-tory parameters and comorbidities were used to investigate the health state profiles by using multiple correspondence analysis and clustering. Logistic regression was used to assess whether LLD prescription was associated with patients’ health state profiles and with short-term mortality. Results: Four clusters of patients were identified according to their health state: two of them (Cluster III and IV) were the epitome of frailty conditions with poor short-term outcomes, whereas the others included healthier patients. The average prevalence of LLD use was 27.6%. The lowest prevalence was found among the healthier patients in Cluster I and among the oldest frail patients with severe functional and cognitive impairment in Cluster IV. The highest prevalence was among multimorbid patients in Cluster III (OR=4.50, 95% CI=3.76–5.38) characterized by a high cardiovascular risk. Being prescribed with LLDs was associated with a lower 3-month mortality, even after adjusting for cluster assignment (OR=0.59; 95% CI = 0.44–0.80). Conclusion: The prevalence of LLD prescription was low and in overall agreement with guideline recommendations and with respect to patients’ health state profiles.
2021
- What changed in the Italian internal medicine and geriatric wards during the lockdown
[Articolo su rivista]
D'Avanzo, B.; Nobili, A.; Tettamanti, M.; Pasina, L.; Mannucci, P. M.; Pietrangelo, A.; Perticone, F.; Violi, F.; Corazza, G. R.; Corrao, S.; Marengoni, A.; Salerno, F.; Cesari, M.; Franchi, C.; Cortesi, L.; Miglio, G.; Ardoino, I.; Novella, A.; Prisco, D.; Silvestri, E.; Emmi, G.; Bettiol, A.; Mattioli, I.; Biolo, G.; Zanetti, M.; Bartelloni, G.; Vanoli, M.; Grignani, G.; Pulixi, E. A.; Lupattelli, G.; Bianconi, V.; Alcidi, R.; Girelli, D.; Busti, F.; Marchi, G.; Barbagallo, M.; Dominguez, L.; Beneduce, V.; Cacioppo, F.; Natoli, G.; Mularo, S.; Raspanti, M.; Zoli, M.; Matacena, M. L.; Orio, G.; Magnolfi, E.; Serafini, G.; Simili, A.; Palasciano, G.; Modeo, M. E.; Di Gennaro, C.; Cappellini, M. D.; Fabio, G.; de Amicis, M. M.; de Luca, G.; Scaramellini, N.; Rossi, P. D.; Damanti, S.; Clerici, M.; Leoni, S.; Di Mauro, A. D.; Di Sabatino, A.; Miceli, E.; Lenti, M. V.; Pisati, M.; Dominioni, C. C.; Pontremoli, R.; Beccati, V.; Nobili, G.; Leoncini, G.; Anastasio, L.; Carbone, M.; Cipollone, F.; Guagnano, M. T.; Rossi, I.; Mancuso, G.; Calipari, D.; Bartone, M.; Delitala, G.; Berria, M.; Delitala, A.; Muscaritoli, M.; Molfino, A.; Petrillo, E.; Giorgi, A.; Gracin, C.; Zuccala, G.; D'Aurizio, G.; Romanelli, G.; Volpini, A.; Lucente, D.; Picardi, A.; Gentilucci, U. V.; Gallo, P.; Bellelli, G.; Corsi, M.; Antonucci, C.; Sidoli, C.; Principato, G.; Arturi, F.; Succurro, E.; Tassone, B.; Giofre, F.; Serra, M. G.; Bleve, M. A.; Brucato, A.; de Falco, T.; Fabris, F.; Bertozzi, I.; Bogoni, G.; Rabuini, M. V.; Prandini, T.; Manfredini, R.; Fabbian, F.; Boari, B.; de Giorgi, A.; Tiseo, R.; Paolisso, G.; Rizzo, M. R.; Catalano, C.; Borghi, C.; Strocchi, E.; Ianniello, E.; Soldati, M.; Schiavone, S.; Bragagni, A.; Sabba, C.; Vella, F. S.; Suppressa, P.; de Vincenzo, G. M.; Comitangelo, A.; Amoruso, E.; Custodero, C.; Fenoglio, L.; Falcetta, A.; Fracanzani, A. L.; Tiraboschi, S.; Cespiati, A.; Oberti, G.; Sigon, G.; Peyvandi, F.; Rossio, R.; Colombo, G.; Agosti, P.; Monzani, V.; Savojardo, V.; Ceriani, G.; Pallini, G.; Montecucco, F.; Ottonello, L.; Caserza, L.; Vischi, G.; Liberato, N. L.; Tognin, T.; Purrello, F.; Di Pino, A.; Piro, S.; Rozzini, R.; Falanga, L.; Pisciotta, M. S.; Bellucci, F. B.; Buffelli, S.; Montrucchio, G.; Peasso, P.; Favale, E.; Poletto, C.; Margaria, C.; Sanino, M.; Guasti, L.; Castiglioni, L.; Maresca, A.; Squizzato, A.; Campiotti, L.; Grossi, A.; Diprizio, R. D.; Bertolotti, M.; Mussi, C.; Lancellotti, G.; Libbra, M. V.; Galassi, M.; Grassi, Y.; Greco, A.; Sciacqua, A.; Perticone, M.; Battaglia, R.; Maio, R.; Stanghellini, V.; Ruggeri, E.; del Vecchio, S.; Salvi, A.; Leonardi, R.; Damiani, G.; Capeci, W.; Mattioli, M.; Martino, G. P.; Biondi, L.; Pettinari, P.; Ghio, R.; Dal Col, A.; Minisola, S.; Colangelo, L.; Cilli, M.; Labbadia, G.; Afeltra, A.; Marigliano, B.; Pipita, M. E.; Castellino, P.; Zanoli, L.; Gennaro, A.; Gaudio, A.; Saracco, V.; Fogliati, M.; Bussolino, C.; Mete, F.; Gino, M.; Vigorito, C.; Cittadini, A.; Moreo, G.; Prolo, S.; Pina, G.; Ballestrero, A.; Ferrando, F.; Gonella, R.; Cerminara, D.; Berra, S.; Dassi, S.; Nava, M. C.; Graziella, B.; Baldassarre, S.; Fragapani, S.; Gruden, G.; Galanti, G.; Mascherini, G.; Petri, C.; Stefani, L.; Girino, M.; Piccinelli, V.; Nasso, F.; Gioffre, V.; Pasquale, M.; Sechi, L.; Catena, C.; Colussi, G.; Cavarape, A.; da Porto, A.; Passariello, N.; Rinaldi, L.; Berti, F.; Famularo, G.; Tarsitani, P.; Castello, R.; Pasino, M.; Ceda, G. P.; Maggio, M. G.; Morganti, S.; Artoni, A.; Grossi, M.; Del Giacco, S.; Firinu, D.; Costanzo, G.; Argiolas, G.; Montalto, G.; Licata, A.; Montalto, F. A.; Corica, F.; Basile, G.; Catalano, A.; Bellone, F.; Principato, C.; Malatino, L.; Stancanelli, B.; Terranova, V.; Di Marca, S.; Di Quattro, R.; la Malfa, L.; Caruso, R.; Mecocci, P.; Ruggiero, C.; Boccardi, V.; Meschi, T.; Ticinesi, A.; Nouvenne, A.; Minuz, P.; Fondrieschi, L.; Imperiale, G. N.; Pirisi, M.; Fra, G. P.; Sola, D.; Bellan, M.; Porta, M.; Riva, P.; Quadri, R.; Larovere, E
abstract
2020
- Humankind versus Virus: Are we winning the battle but losing the war?
[Articolo su rivista]
Gaddi, A. V.; Capello, F.; Andrisano, V.; Aspriello, S. D.; Bertolotti, M.; Bonsanto, F.; Britti, D.; Castagnetti, A.; Casu, G.; Cicero, A.; Cipolla, M.; Cotroneo, A. M.; Cremonesi, A.; Dentali, F.; Dicello, M.; Fragiacomo, C.; Gaddoni, M.; Gardini, G. L.; Gnasso, A.; Guardamagna, O.; Lentini, P.; Lucchin, L.; Manca, M.; Massini, G.; Noera, G.; Ortasi, P.; Pedro, E.; Rinaldi, G.; Romano, P.; Romano, V.; Sabba, C.; Savo, M. T.; Sotis, G.; Tangianu, F.; Tempesta, S.; Visioli, F.; Voci, T. D.; Volpe, R.
abstract
2020
- Instrumental assessment of balance and gait in depression: A systematic review
[Articolo su rivista]
Belvederi Murri, M.; Triolo, F.; Coni, A.; Tacconi, C.; Nerozzi, E.; Escelsior, A.; Respino, M.; Neviani, F.; Bertolotti, M.; Bertakis, K.; Chiari, L.; Zanetidou, S.; Amore, M.
abstract
Psychomotor symptoms of depression are understudied despite having a severe impact on patient outcomes. This review aims to summarize the evidence on motor features of depression assessed with instrumental procedures, and examine age-related differences. We included studies investigating posture, balance and gait ascertained with instrumental measurements among individuals with depressive symptoms or disorders. Studies on subjects with specific physical illnesses were excluded. Methodological quality was assessed with the Newcastle - Ottawa Scale (NOS) and PRISMA guidelines were followed. 33 studies (13 case-control, five cross-sectional, nine longitudinal and six intervention) with overall low-medium quality were included. Different instruments were employed to assess posture (e.g. digital cameras), balance (balance, stepping platform) or gait (e.g. Six-Minute-Walking Test, instrumented walkways). Results suggest that depression in adults is associated with significant impairments of posture, balance and gait. Motor abnormalities among depressed older adults may depend on the interplay of physical diseases, cognitive impairment and mood. Very few intervention studies measured motor symptoms as outcome. Available evidence suggests, however, that antidepressant drugs and physical exercise may be beneficial for motor abnormalities. Despite the lack of high-quality studies, instrumental assessments confirm the presence and importance of motor abnormalities in depression, with potential age-related differences in their pathophysiology.
2020
- Pain and Frailty in Hospitalized Older Adults
[Articolo su rivista]
Ardoino, I.; Franchi, C.; Nobili, A.; Mannucci, P. M.; Corli, O.; Pietrangelo, A.; Perticone, F.; Licata, G.; Violi, F.; Corazza, G. R.; Corrao, S.; Marengoni, A.; Salerno, F.; Cesari, M.; Tettamanti, M.; Pasina, L.; Franchi, C.; Franchi, C.; Cortesi, L.; Tettamanti, M.; Miglio, G.; Tettamanti, M.; Cortesi, L.; Novella, A.; Prisco, D.; Silvestri, E.; Emmi, G.; Bettiol, A.; Mattioli, I.; Biolo, G.; Zanetti, M.; Bartelloni, G.; Vanoli, M.; Grignani, G.; Pulixi, E. A.; Lupattelli, G.; Bianconi, V.; Alcidi, R.; Girelli, D.; Busti, F.; Marchi, G.; Barbagallo, M.; Dominguez, L.; Beneduce, V.; Cacioppo, F.; Corrao, S.; Natoli, G.; Mularo, S.; Raspanti, M.; Zoli, M.; Matacena, M. L.; Orio, G.; Magnolfi, E.; Serafini, G.; Simili, A.; Palasciano, G.; Modeo, M. E.; Di Gennaro, C.; Cappellini, M. D.; Fabio, G.; De Amicis, M. M.; De Luca, G.; Scaramellini, N.; Cesari, M.; Rossi, P. D.; Damanti, S.; Clerici, M.; Leoni, S.; Di Mauro, A. D.; Di Sabatino, A.; Miceli, E.; Lenti, M. V.; Pisati, M.; Dominioni, C. C.; Pontremoli, R.; Beccati, V.; Nobili, G.; Leoncini, G.; Anastasio, L.; Carbone, M.; Cipollone, F.; Guagnano, M. T.; Rossi, I.; Mancuso, G.; Calipari, D.; Bartone, M.; Delitala, G.; Berria, M.; Delitala, A.; Muscaritoli, M.; Molfino, A.; Petrillo, E.; Giorgi, A.; Gracin, C.; Zuccala, G.; D'Aurizio, G.; Romanelli, G.; Marengoni, A.; Volpini, A.; Lucente, D.; Picardi, A.; Gentilucci, U. V.; Gallo, P.; Bellelli, G.; Corsi, M.; Antonucci, C.; Sidoli, C.; Principato, G.; Arturi, F.; Succurro, E.; Tassone, B.; Giofre, F.; Serra, M. G.; Bleve, M. A.; Brucato, A.; De Falco, T.; Fabris, F.; Bertozzi, I.; Bogoni, G.; Rabuini, M. V.; Prandini, T.; Manfredini, R.; Fabbian, F.; Boari, B.; De Giorgi, A.; Tiseo, R.; Paolisso, G.; Rizzo, M. R.; Catalano, C.; Borghi, C.; Strocchi, E.; Ianniello, E.; Soldati, M.; Schiavone, S.; Bragagni, A.; Sabba, C.; Vella, F. S.; Suppressa, P.; De Vincenzo, G. M.; Comitangelo, A.; Amoruso, E.; Custodero, C.; Fenoglio, L.; Falcetta, A.; Fracanzani, A. L.; Tiraboschi, S.; Cespiati, A.; Oberti, G.; Sigon, G.; Peyvandi, F.; Rossio, R.; Colombo, G.; Agosti, P.; Monzani, V.; Savojardo, V.; Ceriani, G.; Salerno, F.; Pallini, G.; Montecucco, F.; Ottonello, L.; Caserza, L.; Vischi, G.; Liberato, N. L.; Tognin, T.; Purrello, F.; Di Pino, A.; Piro, S.; Rozzini, R.; Falanga, L.; Pisciotta, M. S.; Bellucci, F. B.; Buffelli, S.; Montrucchio, G.; Peasso, P.; Favale, E.; Poletto, C.; Margaria, C.; Sanino, M.; Violi, F.; Perri, L.; Guasti, L.; Castiglioni, L.; Maresca, A.; Squizzato, A.; Campiotti, L.; Grossi, A.; Diprizio, R. D.; Bertolotti, M.; Mussi, C.; Lancellotti, G.; Libbra, M. V.; Galassi, M.; Grassi, Y.; Greco, A.; Sciacqua, A.; Perticone, M.; Battaglia, R.; Maio, R.; Stanghellini, V.; Ruggeri, E.; del Vecchio, S.; Salvi, A.; Leonardi, R.; Damiani, G.; Capeci, W.; Mattioli, M.; Martino, G. P.; Biondi, L.; Pettinari, P.; Ghio, R.; Col, A. D.; Minisola, S.; Colangelo, L.; Cilli, M.; Labbadia, G.; Afeltra, A.; Marigliano, B.; Pipita, M. E.; Castellino, P.; Zanoli, L.; Gennaro, A.; Gaudio, A.; Saracco, V.; Fogliati, M.; Bussolino, C.; Mete, F.; Gino, M.; Vigorito, C.; Cittadini, A.; Moreo, G.; Prolo, S.; Pina, G.; Ballestrero, A.; Ferrando, F.; Gonella, R.; Cerminara, D.; Berra, S.; Dassi, S.; Nava, M. C.; Graziella, B.; Baldassarre, S.; Fragapani, S.; Gruden, G.; Galanti, G.; Mascherini, G.; Petri, C.; Stefani, L.; Girino, M.; Piccinelli, V.; Nasso, F.; Gioffre, V.; Pasquale, M.; Sechi, L.; Catena, C.; Colussi, G.; Cavarape, A.; Da Porto, A.; Passariello, N.; Rinaldi, L.; Berti, F.; Famularo, G.; Tarsitani, P.; Castello, R.; Pasino, M.; Ceda, G. P.; Maggio, M. G.; Morganti, S.; Artoni, A.; Grossi, M.; Del Giacco, S.; Firinu, D.; Costanzo, G.; Argiolas, G.; Montalto, G.; Licata, A.; Montalto, F. A.; Corica, F.; Basile, G.; Catalano, A.; Bellone, F.; Principato, C.; Malatino, L.; Stancanelli, B.; Terranova, V.; Di Marca, S.; Di Quattro, R.; La Malfa, L.; Caruso, R.; Mecocci, P.; Ruggiero, C.; Boccardi, V.; Meschi, T.; Ticinesi, A
abstract
Introduction: Pain and frailty are prevalent conditions in the older population. Many chronic diseases are likely involved in their origin, and both have a negative impact on quality of life. However, few studies have analysed their association. Methods: In light of this knowledge gap, 3577 acutely hospitalized patients 65 years or older enrolled in the REPOSI register, an Italian network of internal medicine and geriatric hospital wards, were assessed to calculate the frailty index (FI). The impact of pain and some of its characteristics on the degree of frailty was evaluated using an ordinal logistic regression model after adjusting for age and gender. Results: The prevalence of pain was 24.7%, and among patients with pain, 42.9% was regarded as chronic pain. Chronic pain was associated with severe frailty (OR = 1.69, 95% CI 1.38–2.07). Somatic pain (OR = 1.59, 95% CI 1.23–2.07) and widespread pain (OR = 1.60, 95% CI 0.93–2.78) were associated with frailty. Osteoarthritis was the most common cause of chronic pain, diagnosed in 157 patients (33.5%). Polymyalgia, rheumatoid arthritis and other musculoskeletal diseases causing chronic pain were associated with a lower degree of frailty than osteoarthritis (OR = 0.49, 95%CI 0.28–0.85). Conclusions: Chronic and somatic pain negatively affect the degree of frailty. The duration and type of pain, as well as the underlying diseases associated with chronic pain, should be evaluated to improve the hospital management of frail older people.
2020
- Recommendations for Cardiovascular Prevention During the Sars-Cov-2 Pandemic: An Executive Document by the Board of the Italian Society of Cardiovascular Prevention
[Articolo su rivista]
Volpe, M.; Battistoni, A.; Bellotti, P.; Bellone, S.; Bertolotti, M.; Biffi, A.; Consoli, A.; Corsini, A.; Desideri, G.; Ferri, C.; Modena, M. G.; Nati, G.; Pirro, M.; Rubattu, S.; Tocci, G.; Trimarco, B.; Volpe, R.; de Kreutzenberg, S. V.
abstract
In 2020, the Sars-Cov-2 pandemic is causing a huge and dramatic impact on healthcare systems worldwide. During this emergency, fragile patients suffering from other comorbidities, especially patients susceptible to or affected by cardiovascular disease, are the ones most exposed to the poorer outcomes. Therefore, it is still mandatory to continue to strictly adhere to the rules of cardiovascular prevention. This document aims to provide all doctors with simple and clear recommendations in order to spread useful messages to the widest number of subjects in order to continue the battle against cardiovascular diseases even in times of pandemic.
2020
- Reduced multidrug resistance-associated protein 2 in ticlopidine-induced cholestatic liver injury
[Articolo su rivista]
Gabbi, C.; Bertolotti, M.
abstract
2020
- Risk communication at the time of Coronavirus: are we washing our hand of COVID-19?
[Articolo su rivista]
Capello, Fabio; Baraldini, Laura; Bertolotti, Marco; Bonomini, Mauro; Bovo, Daniele; Britti, Domenico; Caruso, Lorenzo; Castiglione, Gaetano; Casu, Gavino; Cevenini, Matteo; Cipolla, Maurizio; Cipriani, Gabriele; Dentali, Francesco; Dimilta, Michela; Fagioli, Clara; Maria, Soledad; Linarello, Simona; Guido, Alessandro; Marini, Marina; Mistretta, Laura; Modena, Maria Grazia; E Naimoli, Andrea; Noera, Giorgio; Para, Ombretta; Pili, Giuseppe; Rinaldi, Giovanni; Sabatini, Antonio; Santini, Marco; Teresa Savo, Maria; Tangianu, Flavio; Ussia, Giovanni; Visioli, Francesco; Tommaso, Diego; Volpe, Roberto; Vittorino Gaddi, Antonio
abstract
2020
- Social engagement in late life may attenuate the burden of depressive symptoms due to financial strain in childhood
[Articolo su rivista]
Triolo, F.; Sjoberg, L.; Vetrano, D. L.; Darin-Mattsson, A.; Bertolotti, M.; Fratiglioni, L.; Dekhtyar, S.
abstract
Background: It remains poorly understood if childhood financial strain is associated with old-age depression and if active social life may mitigate this relationship. Aims: To investigate the association between childhood financial strain and depressive symptoms during aging; to examine whether late-life social engagement modifies this association. Method: 2884 dementia-free individuals (aged 60+) from the Swedish National study of Aging and Care-Kungsholmen were clinically examined over a 15-year follow-up. Presence of childhood financial strain was ascertained at baseline. Depressive symptoms were repeatedly assessed with the Montgomery–Åsberg Depression Rating Scale. Social engagement comprised information on baseline social network and leisure activities. Linear, logistic and mixed-effect models estimated baseline and longitudinal associations accounting for sociodemographic, clinical, and lifestyle factors. Results: Childhood financial strain was independently associated with a higher baseline level of depressive symptoms (β = 0.37, 95%CI 0.10–0.65), but not with symptom change over time. Relative to those without financial strain and with active social engagement, depressive burden was increased in those without financial strain but with inactive social engagement (β = 0.43, 95%CI: 0.15–0.71), and in those with both financial strain and inactive engagement (β = 0.99, 95%CI: 0.59–1.40). Individuals with financial strain and active social engagement exhibited similar depressive burden as those without financial strain and with active social engagement. Limitations: Recall bias and reverse causality may affect study results, although sensitivity analyses suggest their limited effect. Conclusions: Early-life financial strain may be of lasting importance for old-age depressive symptoms. Active social engagement in late-life may mitigate this association.
2019
- Correction to: Nutraceutical approach for the management of cardiovascular risk - a combination containing the probiotic Bifidobacterium longum BB536 and red yeast rice extract: results from a randomized, double-blind, placebocontrolled study (Nutrition Journal (2019) 18 (13) DOI: 10.1186/s12937-019-0438-2)
[Articolo su rivista]
Ruscica, M.; Pavanello, C.; Gandini, S.; Macchi, C.; Botta, M.; Dall'Orto, D.; Del Puppo, M.; Bertolotti, M.; Bosisio, R.; Mombelli, G.; Sirtori, C. R.; Calabresi, L.; Magni, P.
abstract
Following publication of the original article[1], the authors reported an error in the affiliation of the third author, Sara Gandini. The correct affiliation should read: Division of Epidemiology and Biostatistics, IEO, European Institute of Oncology IRCCS, Milan, Italy.
2019
- Drug prescription and delirium in older inpatients: Results from the nationwide multicenter Italian Delirium Day 2015-2016
[Articolo su rivista]
Aloisi, G.; Marengoni, A.; Morandi, A.; Zucchelli, A.; Cherubini, A.; Mossello, E.; Bo, M.; Di Santo, S. G.; Mazzone, A.; Trabucchi, M.; Cappa, S.; Fimognari, F. L.; Incalzi, R. A.; Gareri, P.; Perticone, F.; Campanini, M.; Montorsi, M.; Latronico, N.; Zambon, A.; Bellelli, G.; Rispoli, V.; Malara, A.; Spadea, F.; Di Cello, S.; Ceravolo, F.; Fabiano, F.; Chiaradia, G.; Gabriele, A.; Lenino, P.; Andrea, T.; Settembrini, V.; Capomolla, D.; Citrino, A.; Scriva, A.; Bruno, I.; Secchi, R.; De Martino, E.; Muccinelli, R.; Villa Del Sole, R. S. A.; Lupi, G.; Paonessa, P.; Fabbri, A.; Passuti, M. T.; Castellari, S.; Po, A.; Gaggioli, G.; Varesi, M.; Moneti, P.; Capurso, S.; Latini, V.; Ghidotti, S.; Riccardelli, F.; Macchi, M.; Rigo, R.; Claudio, P.; Angelo, B.; Flavio, C.; Benedetta, B.; Boffelli, S.; Cassinadri, A.; Franzoni, S.; Spazzini, E.; Andretto, D.; Tonini, G.; Andreani, L.; Coralli, M.; Balotta, A.; Cancelliere, R.; Ballardini, G.; Simoncelli, M.; Mancini, A.; Strazzacapa, M.; Fabio, S.; De Filippi, F.; Giudice, C.; Dentizzi, C.; Azzini, M.; Cazzadori, M.; Mastroeni, V.; Bertassello, P.; Benati, H. S. C.; Nesta, E.; Tobaldini, C.; Guerini, F.; Elena, T.; Mombelloni, P.; Fontanini, F.; Gabriella, L.; Pizzorni, C.; Oliverio, M.; Del Grosso, L. L.; Giavedoni, C.; Bidoli, G.; Mazzei, B.; Corsonello, A.; Fusco, S.; Vena, S.; De Vuono, T.; Maiuri, G.; Luca, F. F.; Andrea, A.; Giovanni, S.; Rossella, N.; Castegnaro, E.; De Rosa, S.; Benvenuti, E.; Del Lungo, I.; Giardini, S.; Giulietti, C.; Mauro, D. B.; Eleonora, B.; Martina, P.; Irene, F.; Riccardo, B.; Federica, S.; Bertoletti, E.; D'Amico, F.; Caronzolo, F.; Grippa, A.; Lombardo, G.; Pipicella, T.; Antonino, S.; Francesco, C.; Valeria, P. G.; Daniela, L.; Domenico, C.; Giorgio, B.; March, A.; Nitti, M. T.; Felici, A.; Pavan, S.; Piazzani, F.; Lunelli, A.; Dimori, S.; Margotta, A.; Soglia, T.; Postacchini, D.; Brunelli, R.; Santini, S.; Francavilla, M.; Macchiati, I.; Sorvillo, F.; Giuli, C.; Mecocci, P.; Longo, A.; Addesi, D.; Rosa, P. C.; Bencardino, G.; Falbo, T.; Grillo, N.; Marco, F.; Mirella, F.; Fanto, F.; Isaia, G.; Pezzilli, S.; Bergamo, D.; Furno, E.; Rrodhe, S.; Lucarini, S.; Dijk, B.; Dall'Acqua, F.; Calvani, D.; Becheri, D.; Giuseppe, M.; Costanza, M.; Vito, A.; Francesca, B.; Magherini, L.; Novella, M.; Franca, B.; Gambardella, P. M. L.; Valente, C.; Ospedale, N.; Ilaria, B.; Alice, F.; Porrino, P.; Ceci, G.; Giuliana, B.; Michela, T.; Eleonora, C.; Ettore, E.; Camellini, C.; Servello, A.; Grassi, A.; Rozzini, R.; Tironi, S.; Grassi, M. G.; Troisi, E.; Carlo, C.; Gabriella, D. S. S.; Flaminia, F.; Federica, R.; Beatrice, P.; Sofia, T.; Gabutto, A.; Quazzo, L.; Rosatello, A.; Suraci, D.; Tagliabue, B.; Perrone, C.; Ferrara, L.; Castagna, A.; Tremolada, M. L.; Giuseppe, C.; Stefano, B.; Davide, O.; Piano, S.; Serviddio, G.; Lo Buglio, A.; Gurrera, T.; Merlo, V.; Rovai, C.; Cotroneo, A. M.; Carlucci, R.; Abbaldo, A.; Monzani, F.; Qasem, A. A.; Bini, G.; Tafuto, S.; Galli, G.; Bruni, A. C.; Mancuso, G.; Mancuso, G.; Calipari, D.; Bernardini, B.; Corsini, C.; Michele, C.; Sara, D. F.; Cagnin, A.; Fragiacomo, F.; Pompanin, S.; Piero, A.; Marco, C.; Zurlo, A.; Guerra, G.; Pala, M.; Menozzi, L.; Delli Gatti, C.; Magon, S.; Roberto, M.; Alfredo, D. G.; Fabio, F.; Ruana, T.; Elisa, M.; Benedetta, B.; Christian, M.; Marco, P.; Massimo, G.; Di Francesco, V.; Faccioli, S.; Pellizzari, L.; Giorgia, F.; Barbagallo, G.; Lunardelli, M. L.; Martini, E.; Ferrari, E.; Macchiarulo, M.; Corneli, M.; Bacci, M.; Battaglia, G.; Anastasio, L.; Lo Storto, M. S.; Seresin, C.; Simonato, M.; Loreggian, M.; Cestonaro, F.; Durando, M.; Latella, R.; Mazzoleni, M.; Russo, G.; Ponte, M.; Valchera, A.; Salustri, G.; Petritola, D.; Costa, A.; Sinforiani, E.; Cotta, M. R.; Piano, S.; Pizio, R. N.; Cester, A.; Formilan, M.; Pietro, B.; Carbone, P.; Cazzaniga, I.; Appollonio, I.; Cereda, D.; Stabile, A.; Xhani, R.; Acampora, R.; Tremolizzo, L.; Federico, P.; Antonio, C.; Valerio, P.; Cesare, B.; Zhirajr
abstract
Objective: This study aimed to evaluate the association between polypharmacy and delirium, the association of specific drug categories with delirium, and the differences in drug-delirium association between medical and surgical units and according to dementia diagnosis. Methods: Data were collected during 2 waves of Delirium Day, a multicenter delirium prevalence study including patients (aged 65 years or older) admitted to acute and long-term care wards in Italy (2015-2016); in this study, only patients enrolled in acute hospital wards were selected (n = 4,133). Delirium was assessed according to score on the 4 "A's" Test. Prescriptions were classified by main drug categories; polypharmacy was defined as a prescription of drugs from 5 or more classes. Results: Of 4,133 participants, 969 (23.4%) had delirium. The general prevalence of polypharmacy was higher in patients with delirium (67.6% vs 63.0%, P =.009) but varied according to clinical settings. After adjustment for confounders, polypharmacy was associated with delirium only in patients admitted to surgical units (OR = 2.9; 95% CI, 1.4-6.1). Insulin, antibiotics, antiepileptics, antipsychotics, and atypical antidepressants were associated with delirium, whereas statins and angiotensin receptor blockers exhibited an inverse association. A stronger association was seen between typical and atypical antipsychotics and delirium in subjects free from dementia compared to individuals with dementia (typical: OR = 4.31; 95% CI, 2.94-6.31 without dementia vs OR = 1.64; 95% CI, 1.19-2.26 with dementia; atypical: OR = 5.32; 95% CI, 3.44-8.22 without dementia vs OR = 1.74; 95% CI, 1.26-2.40 with dementia). The absence of antipsychotics among the prescribed drugs was inversely associated with delirium in the whole sample and in both of the hospital settings, but only in patients without dementia. Conclusions: Polypharmacy is significantly associated with delirium only in surgical units, raising the issue of the relevance of medication review in different clinical settings. Specific drug classes are associated with delirium depending on the clinical setting and dementia diagnosis, suggesting the need to further explore this relationship.
2019
- Drug-Induced Liver Injury - Types and Phenotypes
[Articolo su rivista]
Gabbi, C; Bertolotti, M
abstract
2019
- Hospital Care of Older Patients With COPD: Adherence to International Guidelines for Use of Inhaled Bronchodilators and Corticosteroids
[Articolo su rivista]
Proietti, Marco; Agosti, Pasquale; Lonati, Chiara; Corrao, Salvatore; Perticone, Francesco; Mannucci, Pier Mannuccio; Nobili, Alessandro; Harari, SERGIO ALFONSO; Tettamanti, Mauro; Pasina, Luca; Franchi, Carlotta; Marengoni, Alessandra; Salerno, Francesco; Cesari, Matteo; Licata, Giuseppe; Violi, Francesco; Corazza, Gino Roberto; Cortesi, Laura; Ardoino, Ilaria; Prisco, Domenico; Silvestri, Elena; Cenci, Caterina; Emmi, Giacomo; Biolo, Gianni; Zanetti, Michela; Guadagni, Martina; Zaccari, Michele; Vanoli, Massimo; Grignani, Giulia; Pulixi, Edoardo Alessandro; Bernardi, Mauro; Bassi, Silvia Li; Santi, Luca; Zaccherini, Giacomo; Mannarino, Elmo; Lupattelli, Graziana; Bianconi, Vanessa; Paciullo, Francesco; Nuti, Ranuccio; Valenti, Roberto; Ruvio, Martina; Cappelli, Silvia; Palazzuoli, Alberto; Olivieri, Oliviero; Girelli, Domenico; Matteazzi, Thomas; Barbagallo, Mario; Dominguez, Ligia; Cocita, Floriana; Beneduce, Vincenza; Plances, Lidia; Zoli, Marco; Lazzari, Ilaria; Brunori, Mattia; Pasini, Franco Laghi; Capecchi, Pier Leopoldo; Palasciano, Giuseppe; Modeo, Maria Ester; Di Gennaro, Carla; Cappellini, Maria Domenica; Maira, Diletta; Di Stefano, Valeria; Fabio, Giovanna; Seghezzi, Sonia; Mancarella, Marta; Rossi, Paolo Dionigi; Damanti, Sarah; Clerici, Marta; Conti, Federica; Miceli, Emanuela; Lenti, Marco Vincenzo; Pisati, Martina; Dominioni, Costanza Caccia; Murialdo, Giovanni; Marra, Alessio; Cattaneo, Federico; Pontremoli, Roberto; Secchi, Maria Beatrice; Ghelfi, Davide; Anastasio, Luigi; Sofia, Lucia; Carbone, Maria; Cipollone, Francesco; Guagnano, Maria Teresa; Angelucci, Ermanno; Valeriani, Emanuele; Mancuso, Gerardo; Calipari, Daniela; Bartone, Mosè; Delitala, Giuseppe; Berria, Maria; Muscaritoli, Maurizio; Molfino, Alessio; Petrillo, Enrico; Zuccalà, Giuseppe; D'Aurizio, Gabriella; Romanelli, Giuseppe; Zucchelli, Alberto; Picardi, Antonio; Gentilucci, Umberto Vespasiani; Gallo, Paolo; Dell'Unto, Chiara; Annoni, Giorgio; Corsi, Maurizio; Bellelli, Giuseppe; Zazzetta, Sara; Mazzola, Paolo; Szabo, Hajnalka; Bonfanti, Alessandra; Arturi, Franco; Succurro, Elena; Rubino, Mariangela; Serra, Maria Grazia; Bleve, Maria Antonietta; Gasbarrone, Laura; Sajeva, Maria Rosaria; Brucato, Antonio; Ghidoni, Silvia; Fabris, Fabrizio; Bertozzi, Irene; Bogoni, Giulia; Rabuini, Maria Victoria; Cosi, Elisabetta; Manfredini, Roberto; Fabbian, Fabio; Boari, Benedetta; De Giorgi, Alfredo; Tiseo, Ruana; Paolisso, Giuseppe; Rizzo, Maria Rosaria; Borghi, Claudio; Strocchi, Enrico; De Sando, Valeria; Pareo, Ilenia; Sabbà, Carlo; Vella, Francesco Saverio; Suppressa, Patrizia; Schilardi, Andrea; Loparco, Francesca; Fenoglio, Luigi; Bracco, Christian; Giraudo, Alessia Valentina; Fargion, Silvia; Periti, Giulia; Porzio, Marianna; Tiraboschi, Slivia; Peyvandi, Flora; Rossio, Raffaella; Ferrari, Barbara; Colombo, Giulia; Monzani, Valter; Savojardo, Valeria; Folli, Christian; Ceriani, Giuliana; Pallini, Giada; Dallegri, Franco; Ottonello, Luciano; Liberale, Luca; Caserza, Lara; Salam, Kassem; Liberato, Nicola Lucio; Tognin, Tiziana; Bianchi, Giovanni Battista; Giaquinto, Sabrina; Purrello, Francesco; Di Pino, Antonino; Piro, Salvatore; Rozzini, Renzo; Falanga, Lina; Spazzini, Elena; Ferrandina, Camillo; Montrucchio, Giuseppe; Petitti, Paolo; Salmi, Raffaella; Gaudenzi, Piergiorgio; Perri, Ludovica; Landolfi, Raffaele; Montalto, Massimo; Mirijello, Antonio; Guasti, Luigina; Castiglioni, Luana; Maresca, Andrea; Squizzato, Alessandro; Molaro, Marta; Grossi, Alessandra; Bertolotti, Marco; Mussi, Chiara; Libbra, Maria Vittoria; Dondi, Giulia; Pellegrini, Elisa; Carulli, Lucia; Colangelo, Lidia; Falbo, Tania; Stanghellini, Vincenzo; De Giorgio, Roberto; Ruggeri, Eugenio; Vecchio, Sara del; Salvi, Andrea; Leonardi, Roberto; Damiani, Giampaolo; Gabrielli, Armando; Capeci, William; Mattioli, Massimo; Martino, Giuseppe Pio; Biondi, Lorenzo; Pettinari, Pietro; Ghio, Riccardo; Col, Anna Dal; Minisola, Salvatore; Cola
abstract
Objectives: We aimed to analyze the prevalence and impact of COPD in older patients hospitalized in internal medicine or geriatric wards, and to investigate adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, associated clinical factors, and outcomes. Design: Data were obtained from REgistro POliterapie SIMI (REPOSI), a prospective multicenter observational registry that enrolls inpatients aged ≥65 years. Setting and Participants: Older hospitalized patients enrolled from 2008 to 2016 with a diagnosis of COPD. Measures: We evaluated adherence to the 2018 GOLD guidelines at admission and discharge, by examining the prescription of inhaled bronchodilators and corticosteroids in COPD patients. We also evaluated the occurrence of outcomes and its association with COPD and guideline adherence. Results: At hospital admission, COPD was diagnosed in 1302 (21.5%) of 6046 registered patients. COPD patients were older, with more impaired clinical and functional status and multiple comorbidities. Overall, 34.3% of COPD patients at admission and 35.6% at discharge were adherent to the GOLD guidelines. Polypharmacy (≥5 drugs) at admission [odds ratio (OR): 3.28, 95% confidence interval (CI): 2.24-4.81], a history of acute COPD exacerbation (OR: 2.65, 95% CI: 1.44-4.88) at admission, smoking habit (OR: 1.45, 95% CI: 1.08-1.94), and polypharmacy at discharge (OR: 6.76, 95% CI: 4.15-11.0) were associated with adherence to guidelines. COPD was independently associated with the risk of cardiovascular and respiratory death and rehospitalization occurrence compared to patients without COPD during follow-up. Adherence to guidelines was inversely associated with the occurrence of death from all causes (OR: 0.12, 95% CI: 0.02-0.90). Conclusions/Implications: COPD was common in older patients acutely hospitalized, showing an impaired functional and clinical status. Prescriptions for older COPD patients were often not adherent to GOLD guidelines. Poor adherence to guidelines was associated with a worse clinical status. There is a need to improve adherence to guidelines in treating COPD patients, with the ultimate goal of reducing clinical events.
2019
- Management of high cholesterol levels in older people
[Articolo su rivista]
Bertolotti, M.; Lancellotti, G.; Mussi, C.
abstract
The management of hypercholesterolemia in older adults still represents a challenge in clinical medicine. The pathophysiological alterations of cholesterol metabolism associated with aging are still incompletely understood, even if epidemiological evidence suggests that serum cholesterol levels increase with ongoing age, possibly with a plateau after the age of 80 years. Age is also one of the main determinants of cardiovascular disease, according to all cardiovascular risk estimate tools. Cholesterol-lowering treatment, therefore, would be expected to bring significant protection, even in these patients. Unfortunately, direct experimental evidence is extremely limited, particularly in the very old age strata of the population; a clinical benefit still seems to be present, but the risk for drug-related adverse events is clearly higher. At any rate, at the present time, definite guidelines for the correct management of hypercholesterolemia in older patients are not available. Therefore, the decision whether or not a pharmacological treatment should be set up, and the choice of the drug, need to be tailored to the individual patient, and requires accurate clinical judgment. The specific aspects of frailty and disability, along with the actual age of the patients, have to be considered together, with a comprehensive assessment approach. The present review summarizes the evidence regarding the modifications of cholesterol metabolism in older patients, the impact of lipid-lowering drugs on cardiovascular outcomes and focuses on the considerations that can help to define the most appropriate treatment strategy, in view of the individual functional profile. Geriatr Gerontol Int 2019; 19: 375-383.
2019
- Mortality rate and risk factors for gastrointestinal bleeding in elderly patients
[Articolo su rivista]
Lenti, M. V.; Pasina, L.; Cococcia, S.; Cortesi, L.; Miceli, E.; Dominioni, C. C.; Pisati, M.; Mengoli, C.; Perticone, F.; Nobili, A.; Di Sabatino, A.; Corazza, G. R.; Mannucci, P. M.; Tettamanti, M.; Franchi, C.; Corrao, S.; Marengoni, A.; Salerno, F.; Cesari, M.; Licata, G.; Violi, F.; Ardoino, I.; Prisco, D.; Silvestri, E.; Cenci, C.; Emmi, G.; Biolo, G.; Zanetti, M.; Guadagni, M.; Zaccari, M.; Vanoli, M.; Grignani, G.; Pulixi, E. A.; Bernardi, M.; Bassi, S. L.; Santi, L.; Zaccherini, G.; Mannarino, E.; Lupattelli, G.; Bianconi, V.; Paciullo, F.; Nuti, R.; Valenti, R.; Ruvio, M.; Cappelli, S.; Palazzuoli, A.; Olivieri, O.; Girelli, D.; Matteazzi, T.; Barbagallo, M.; Dominguez, L.; Cocita, F.; Beneduce, V.; Plances, L.; Zoli, M.; Lazzari, I.; Brunori, M.; Pasini, F. L.; Capecchi, P. L.; Palasciano, G.; Modeo, M. E.; Di Gennaro, C.; Cappellini, M. D.; Maira, D.; Di Stefano, V.; Fabio, G.; Seghezzi, S.; Mancarella, M.; Rossi, P. D.; Damanti, S.; Clerici, M.; Conti, F.; Murialdo, G.; Marra, A.; Cattaneo, F.; Pontremoli, R.; Secchi, M. B.; Ghelfi, D.; Anastasio, L.; Sofia, L.; Carbone, M.; Cipollone, F.; Guagnano, M. T.; Angelucci, E.; Valeriani, E.; Mancuso, G.; Calipari, D.; Bartone, M.; Delitala, G.; Berria, M.; Muscaritoli, M.; Molfino, A.; Petrillo, E.; ZuccalA, G.; D'aurizio, G.; Romanelli, G.; Zucchelli, A.; Picardi, A.; Gentilucci, U. V.; Gallo, P.; Dell'unto, C.; Annoni, G.; Corsi, M.; Bellelli, G.; Zazzetta, S.; Mazzola, P.; Szabo, H.; Bonfanti, A.; Arturi, F.; Succurro, E.; Rubino, M.; Serra, M. G.; Bleve, M. A.; Gasbarrone, L.; Sajeva, M. R.; Brucato, A.; Ghidoni, S.; Fabris, F.; Bertozzi, I.; Bogoni, G.; Rabuini, M. V.; Cosi, E.; Manfredini, R.; Fabbian, F.; Boari, B.; De Giorgi, A.; Tiseo, R.; Paolisso, G.; Rizzo, M. R.; Borghi, C.; Strocchi, E.; De Sando, V.; Pareo, I.; SabbA, C.; Vella, F. S.; Suppressa, P.; Agosti, P.; Schilardi, A.; Loparco, F.; Fenoglio, L.; Bracco, C.; Giraudo, A. V.; Fargion, S.; Periti, G.; Porzio, M.; Tiraboschi, S.; Peyvandi, F.; Rossio, R.; Ferrari, B.; Colombo, G.; Monzani, V.; Savojardo, V.; Folli, C.; Ceriani, G.; Pallini, G.; Dallegri, F.; Ottonello, L.; Liberale, L.; Caserza, L.; Salam, K.; Liberato, N. L.; Tognin, T.; Bianchi, G. B.; Giaquinto, S.; Purrello, F.; Di Pino, A.; Piro, S.; Rozzini, R.; Falanga, L.; Spazzini, E.; Ferrandina, C.; Montrucchio, G.; Petitti, P.; Salmi, R.; Gaudenzi, P.; Perri, L.; Landolfi, R.; Montalto, M.; Mirijello, A.; Guasti, L.; Castiglioni, L.; Maresca, A.; Squizzato, A.; Molaro, M.; Grossi, A.; Bertolotti, M.; Mussi, C.; Libbra, M. V.; Dondi, G.; Pellegrini, E.; Carulli, L.; Colangelo, L.; Falbo, T.; Stanghellini, V.; Giorgio, R. D.; Ruggeri, E.; Vecchio, S.; Salvi, A.; Leonardi, R.; Damiani, G.; Gabrielli, A.; Capeci, W.; Mattioli, M.; Martino, G. P.; Biondi, L.; Pettinari, P.; Ghio, R.; Col, A. D.; Minisola, S.; Colangelo, L.; Afeltra, A.; Marigliano, B.; Pipita, M. E.; Castellino, P.; Blanco, J.; Zanoli, L.; Pignataro, S.; Saracco, V.; Fogliati, M.; Bussolino, C.; Mete, F.; Gino, M.; Cittadini, A.; Vigorito, C.; Arcopinto, M.; Salzano, A.; Bobbio, E.; Marra, A. M.; Sirico, D.; Moreo, G.; Gasparini, F.; Prolo, S.; Pina, G.; Ballestrero, A.; Ferrando, F.; Berra, S.; Dassi, S.; Nava, M. C.; Graziella, B.; Baldassarre, S.; Fragapani, S.; Gruden, G.; Galanti, G.; Mascherini, G.; Petri, C.; Stefani, L.; Girino, M.; Piccinelli, V.; Nasso, F.; GioffrA, V.; Pasquale, M.; Scattolin, G.; Martinelli, S.; Turrin, M.; Sechi, L.; Catena, C.; Colussi, G.; Passariello, N.; Rinaldi, L.; Berti, F.; Famularo, G.; Patrizia, T.; Castello, R.; Pasino, M.; Ceda, G. P.; Maggio, M. G.; Morganti, S.; Artoni, A.; Giacco, S. D.; Firinu, D.; Losa, F.; Paoletti, G.; Montalto, G.; Licata, A.; Malerba, V.; Antonino, L.; Basile, G.; Antonino, C.; Malatino, L.; Stancanelli, B.; Terranova, V.; Di Marca, S.; Mecocci, P.; Ruggiero, C.; Boccardi, V.; Meschi, T.; Lauretani, F.; Ticinesi, A.; Minuz, P.; Fondrieschi, L.; Pirisi, M.; Fra, G. P.; Sola, D.; Porta, M.; Riva, P.; Quadri, R.; S
abstract
Background: Gastrointestinal bleeding (GIB) is burdened by high mortality rate that increases with aging. Elderly patients may be exposed to multiple risk factors for GIB. We aimed at defining the impact of GIB in elderly patients. Methods: Since 2008, samples of elderly patients (age ≥ 65 years) with multimorbidity admitted to 101 internal medicine wards across Italy have been prospectively enrolled and followed-up (REPOSI registry). Diagnoses of GIB, length of stay (LOS), mortality rate, and possible risk factors, including drugs, index of comorbidity (Cumulative Illness Rating Scale [CIRS]), polypharmacy, and chronic diseases were assessed. Adjusted multivariate logistic regression models were computed. Results: 3872 patients were included (mean age 79 ± 7.5 years, F:M ratio 1.1:1). GIB was reported in 120 patients (mean age 79.6 ± 7.3 years, F:M 0.9:1), with a crude prevalence of 3.1%. Upper GIB occurred in 72 patients (mean age 79.3 ± 7.6 years, F:M 0.8:1), lower GIB in 51 patients (mean age 79.4 ± 7.1 years, F:M 0.9:1), and both upper/lower GIB in 3 patients. Hemorrhagic gastritis/duodenitis and colonic diverticular disease were the most common causes. The LOS of patients with GIB was 11.7 ± 8.1 days, with a 3.3% in-hospital and a 9.4% 3-month mortality rates. Liver cirrhosis (OR 5.64; CI 2.51–12.65), non-ASA antiplatelet agents (OR 2.70; CI 1.23–5.90), and CIRS index of comorbidity >3 (OR 2.41; CI 1.16–4.98) were associated with GIB (p < 0.05). Conclusions: A high index of comorbidity is associated with high odds of GIB in elderly patients. The use of non-ASA antiplatelet agents should be discussed in patients with multimorbidity.
2019
- Need for deprescribing in hospital elderly patients discharged with a limited life expectancy: The REPOSI study
[Articolo su rivista]
Pasina, L.; Ottolini, B. B.; Cortesi, L.; Tettamanti, M.; Franchi, C.; Marengoni, A.; Mannucci, P. M.; Nobili, A.; Corrao, S.; Salerno, F.; Cesari, M.; Perticone, F.; Licata, G.; Violi, F.; Corazza, G. R.; Ardoino, I.; Prisco, D.; Silvestri, E.; Cenci, C.; Emmi, G.; Biolo, G.; Zanetti, M.; Guadagni, M.; Zaccari, M.; Vanoli, M.; Grignani, G.; Pulixi, E. A.; Bernardi, M.; Bassi, S. L.; Santi, L.; Zaccherini, G.; Mannarino, E.; Lupattelli, G.; Bianconi, V.; Paciullo, F.; Nuti, R.; Valenti, R.; Ruvio, M.; Cappelli, S.; Palazzuoli, A.; Olivieri, O.; Girelli, D.; Matteazzi, T.; Barbagallo, M.; Dominguez, L.; Cocita, F.; Beneduce, V.; Plances, L.; Zoli, M.; Lazzari, I.; Brunori, M.; Pasini, F. L.; Capecchi, P. L.; Palasciano, G.; Modeo, M. E.; Di Gennaro, C.; Cappellini, M. D.; Maira, D.; Di Stefano, V.; Fabio, G.; Seghezzi, S.; Mancarella, M.; Rossi, P. D.; Damanti, S.; Clerici, M.; Conti, F.; Miceli, E.; Lenti, M. V.; Pisati, M.; Dominioni, C. C.; Murialdo, G.; Marra, A.; Cattaneo, F.; Secchi, M. B.; Ghelfi, D.; Anastasio, L.; Sofia, L.; Carbone, M.; Cipollone, F.; Guagnano, M. T.; Angelucci, E.; Valeriani, E.; Mancuso, G.; Calipari, D.; Bartone, M.; Delitala, G.; Berria, M.; Muscaritoli, M.; Molfino, A.; Petrillo, E.; Zuccala, G.; D'Aurizio, G.; Romanelli, G.; Zucchelli, A.; Picardi, A.; Gentilucci, U. V.; Gallo, P.; Dell'Unto, C.; Annoni, G.; Corsi, M.; Bellelli, G.; Zazzetta, S.; Mazzola, P.; Szabo, H.; Bonfanti, A.; Arturi, F.; Succurro, E.; Rubino, M.; Serra, M. G.; Bleve, M. A.; Gasbarrone, L.; Sajeva, M. R.; Brucato, A.; Ghidoni, S.; Fabris, F.; Bertozzi, I.; Bogoni, G.; Rabuini, M. V.; Cosi, E.; Manfredini, R.; Fabbian, F.; Boari, B.; De Giorgi, A.; Tiseo, R.; Paolisso, G.; Rizzo, M. R.; Borghi, C.; Strocchi, E.; De Sando, V.; Pareo, I.; Sabba, C.; Vella, F. S.; Suppressa, P.; Agosti, P.; Schilardi, A.; Loparco, F.; Fenoglio, L.; Bracco, C.; Giraudo, A. V.; Fargion, S.; Periti, G.; Porzio, M.; Tiraboschi, S.; Peyvandi, F.; Rossio, R.; Ferrari, B.; Colombo, G.; Monzani, V.; Savojardo, V.; Folli, C.; Ceriani, G.; Pallini, G.; Dallegri, F.; Ottonello, L.; Liberale, L.; Caserza, L.; Salam, K.; Liberato, N. L.; Tognin, T.; Bianchi, G. B.; Giaquinto, S.; Purrello, F.; Di Pino, A.; Piro, S.; Rozzini, R.; Falanga, L.; Spazzini, E.; Ferrandina, C.; Montrucchio, G.; Petitti, P.; Salmi, R.; Gaudenzi, P.; Perri, L.; Landolfi, R.; Montalto, M.; Mirijello, A.; Guasti, L.; Castiglioni, L.; Maresca, A.; Squizzato, A.; Molaro, M.; Grossi, A.; Bertolotti, M.; Mussi, C.; Libbra, M. V.; Dondi, G.; Pellegrini, E.; Carulli, L.; Colangelo, L.; Falbo, T.; Stanghellini, V.; De Giorgio, R.; Ruggeri, E.; Del Vecchio, S.; Salvi, A.; Leonardi, R.; Damiani, G.; Gabrielli, A.; Capeci, W.; Mattioli, M.; Martino, G. P.; Biondi, L.; Pettinari, P.; Ghio, R.; Dal Col, A.; Minisola, S.; Colangelo, L.; Afeltra, A.; Marigliano, B.; Pipita, M. E.; Castellino, P.; Blanco, J.; Zanoli, L.; Pignataro, S.; Saracco, V.; Fogliati, M.; Bussolino, C.; Mete, F.; Gino, M.; Cittadini, A.; Vigorito, C.; Arcopinto, M.; Salzano, A.; Bobbio, E.; Marra, A. M.; Sirico, D.; Moreo, G.; Gasparini, F.; Prolo, S.; Pina, G.; Ballestrero, A.; Ferrando, F.; Berra, S.; Dassi, S.; Nava, M. C.; Graziella, B.; Baldassarre, S.; Fragapani, S.; Gruden, G.; Galanti, G.; Mascherini, G.; Petri, C.; Stefani, L.; Girino, M.; Piccinelli, V.; Nasso, F.; Gioffre, V.; Pasquale, M.; Scattolin, G.; Martinelli, S.; Turrin, M.; Sechi, L.; Catena, C.; Colussi, G.; Passariello, N.; Rinaldi, L.; Berti, F.; Famularo, G.; Patrizia, T.; Castello, R.; Pasino, M.; Ceda, G. P.; Maggio, M. G.; Morganti, S.; Artoni, A.; Del Giacco, S.; Firinu, D.; Losa, F.; Paoletti, G.; Montalto, G.; Licata, A.; Malerba, V.; Antonino, L.; Basile, G.; Antonino, C.; Malatino, L.; Stancanelli, B.; Terranova, V.; Di Marca, S.; Mecocci, P.; Ruggiero, C.; Boccardi, V.; Meschi, T.; Lauretani, F.; Ticinesi, A.; Minuz, P.; Fondrieschi, L.; Pirisi, M.; Fra, G. P.; Sola, D.; Porta, M.; Riva, P.; Quadri, R.; Scanzi, G.; Mengoli, C.; Provini, S.;
abstract
Objective: Older people approaching the end of life are at a high risk for adverse drug reactions. Approaching the end of life should change the therapeutic aims, triggering a reduction in the number of drugs. The main aim of this study is to describe the preventive and symptomatic drug treatments prescribed to patients discharged with a limited life expectancy from internal medicine and geriatric wards. The secondary aim was to describe the potentially severe drug-drug interactions (DDI). Materials and Methods: We analyzed Registry of Polytherapies Societa Italiana di Medicina Interna (REPOSI), a network of internal medicine and geriatric wards, to describe the drug therapy of patients discharged with a limited life expectancy. Results: The study sample comprised 55 patients discharged with a limited life expectancy. Patients with at least 1 preventive medication that could be considered for deprescription at the end of life were significantly fewer from admission to discharge (n = 30; 54.5% vs. n = 21; 38.2%; p = 0.02). Angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, lipid-lowering drugs, and clonidine were the most frequent potentially avoidable medications prescribed at discharge, followed by xanthine oxidase inhibitors and drugs to prevent fractures. Thirty-seven (67.3%) patients were also exposed to at least 1 potentially severe DDI at discharge. Conclusion: Hospital discharge is associated with a small reduction in the use of commonly prescribed preventive medications in patients discharged with a limited life expectancy. Cardiovascular drugs are the most frequent potentially avoidable preventive medications. A consensus framework or shared criteria for potentially inappropriate medication in elderly patients with limited life expectancy could be useful to further improve drug prescription.
2019
- Nutraceutical approach for the management of cardiovascular risk – a combination containing the probiotic Bifidobacterium longum BB536 and red yeast rice extract: results from a randomized, double-blind, placebo-controlled study
[Articolo su rivista]
Ruscica, Massimiliano; Pavanello, Chiara; Gandini, Sara; Macchi, Chiara; Botta, Margherita; Dall’Orto, Daria; Del Puppo, Marina; Bertolotti, Marco; Bosisio, Raffaella; Mombelli, Giuliana; Sirtori, Cesare R.; Calabresi, Laura; Magni, Paolo
abstract
BACKGROUND:
Probiotics incorporated into dairy products have been shown to reduce total (TC) and LDL cholesterolemia (LDL-C) in subjects with moderate hypercholesterolemia. More specifically, probiotics with high biliary salt hydrolase activity, e.g. Bifidobacterium longum BB536, may decrease TC and LDL-C by lowering intestinal cholesterol reabsorption and, combined with other nutraceuticals, may be useful to manage hypercholesterolemia in subjects with low cardiovascular (CV) risk. This study was conducted to evaluate the efficacy and safety of a nutraceutical combination containing Bifidobacterium longum BB536, red yeast rice (RYR) extract (10 mg/day monacolin K), niacin, coenzyme Q10 (Lactoflorene Colesterolo®). The end-points were changes of lipid CV risk markers (LDL-C, TC, non-HDL-cholesterol (HDL-C), triglycerides (TG), apolipoprotein B (ApoB), HDL-C, apolipoprotein AI (ApoAI), lipoprotein(a) (Lp(a), proprotein convertase subtilisin/kexin type 9 (PCSK9)), and of markers of cholesterol synthesis/absorption.
METHODS:
A 12-week randomized, parallel, double-blind, placebo-controlled study. Thirty-three subjects (18-70 years) in primary CV prevention and low CV risk (SCORE: 0-1% in 24 and 2-4% in 9 subjects; LDL-C: 130-200 mg/dL) were randomly allocated to either nutraceutical (N = 16) or placebo (N = 17).
RESULTS:
Twelve-week treatment with the nutraceutical combination, compared to placebo, significantly reduced TC (- 16.7%), LDL-C (- 25.7%), non-HDL-C (- 24%) (all p < 0.0001), apoB (- 17%, p = 0.003). TG, HDL-C, apoAI, Lp(a), PCSK9 were unchanged. Lathosterol:TC ratio was significantly reduced by the nutraceutical combination, while campesterol:TC ratio and sitosterol:TC ratio did not change, suggesting reduction of synthesis without increased absorption of cholesterol. No adverse effects and a 97% compliance were observed.
CONCLUSIONS:
A 12-week treatment with a nutraceutical combination containing the probiotic Bifidobacterium longum BB536 and RYR extract significantly improved the atherogenic lipid profile and was well tolerated by low CV risk subjects.
TRIAL REGISTRATION:
NCT02689934 .
2019
- Patterns of infections in older patients acutely admitted to medical wards: data from the REPOSI register
[Articolo su rivista]
Rossio, R.; Ardoino, I.; Franchi, C.; Nobili, A.; Mannuccio Mannucci, P.; Peyvandi, F.; Prisco, D.; Silvestri, E.; Emmi, G.; Bettiol, A.; Caterina, C.; Biolo, G.; Zanetti, M.; Guadagni, M.; Zaccari, M.; Chiuch, M.; Vanoli, M.; Grignani, G.; Pulixi, E. A.; Bernardi, M.; Bassi, S. L.; Santi, L.; Zaccherini, G.; Lupattelli, G.; Mannarino, E.; Bianconi, V.; Paciullo, F.; Alcidi, R.; Nuti, R.; Valenti, R.; Ruvio, M.; Cappelli, S.; Palazzuoli, A.; Girelli, D.; Busti, F.; Marchi, G.; Barbagallo, M.; Dominguez, L.; Cocita, F.; Beneduce, V.; Plances, L.; Corrao, S.; Natoli, G.; Mularo, S.; Raspanti, M.; Cavallaro, F.; Zoli, M.; Lazzari, I.; Brunori, M.; Fabbri, E.; Magalotti, D.; Arno, R.; Pasini, F. L.; Capecchi, P. L.; Palasciano, G.; Modeo, M. E.; Di Gennaro, C.; Cappellini, M. D.; Maira, D.; Di Stefano, V.; Fabio, G.; Seghezzi, S.; Mancarella, M.; De Amicis, M. M.; De Luca, G.; Scaramellini, N.; Cesari, M.; Rossi, P. D.; Damanti, S.; Clerici, M.; Conti, F.; Bonini, G.; Ottolini, B. B.; Di Sabatino, A.; Miceli, E.; Lenti, M. V.; Pisati, M.; Dominioni, C. C.; Murialdo, G.; Marra, A.; Cattaneo, F.; Pontremoli, R.; Beccati, V.; Nobili, G.; Secchi, M. B.; Ghelfi, D.; Anastasio, L.; Sofia, L.; Carbone, M.; Cipollone, F.; Guagnano, M. T.; Valeriani, E.; Rossi, I.; Mancuso, G.; Calipari, D.; Bartone, M.; Delitala, G.; Berria, M.; Pes, C.; Delitala, A.; Muscaritoli, M.; Molfino, A.; Petrillo, E.; Zuccala, G.; D'Aurizio, G.; Romanelli, G.; Marengoni, A.; Zucchelli, A.; Manzoni, F.; Volpini, A.; Picardi, A.; Gentilucci, U. V.; Gallo, P.; Dell'Unto, C.; Annoni, G.; Corsi, M.; Bellelli, G.; Zazzetta, S.; Mazzola, P.; Szabo, H.; Bonfanti, A.; Arturi, F.; Succurro, E.; Rubino, M.; Tassone, B.; Sesti, G.; Serra, M. G.; Bleve, M. A.; Gasbarrone, L.; Sajeva, M. R.; Brucato, A.; Ghidoni, S.; Fabris, F.; Bertozzi, I.; Bogoni, G.; Rabuini, M. V.; Cosi, E.; Scarinzi, P.; Amabile, A.; Omenetto, E.; Prandini, T.; Manfredini, R.; Fabbian, F.; Boari, B.; De Giorgi, A.; Tiseo, R.; De Giorgio, R.; Paolisso, G.; Rizzo, M. R.; Borghi, C.; Strocchi, E.; Ianniello, E.; Soldati, M.; Sabba, C.; Vella, F. S.; Suppressa, P.; Agosti, P.; Schilardi, A.; Loparco, F.; De Vincenzo, G. M.; Comitangelo, A.; Amoruso, E.; Fenoglio, L.; Falcetta, A.; Bracco, C.; Fracanzani Silvia Fargion, A. L.; Tiraboschi, S.; Cespiati, A.; Oberti, G.; Sigon, G.; Ferrari, B.; Colombo, G.; Monzani, V.; Savojardo, V.; Folli, C.; Ceriani, G.; Salerno, F.; Pallini, G.; Dallegri, F.; Ottonello, L.; Liberale, L.; Caserza, L.; Salam, K.; Liberato, N. L.; Tognin, T.; Bianchi, G. B.; Giaquinto, S.; Purrello, F.; Di Pino, A.; Piro, S.; Rozzini, R.; Falanga, L.; Spazzini, E.; Ferrandina, C.; Montrucchio, G.; Petitti, P.; Peasso, P.; Favale, E.; Poletto, C.; Salmi, R.; Gaudenzi, P.; Violi, F.; Perri, L.; Landolfi, R.; Montalto, M.; Mirijello, A.; Guasti, L.; Castiglioni, L.; Maresca, A.; Squizzato, A.; Campiotti, L.; Grossi, A.; Bertolotti, M.; Mussi, C.; Lancellotti, G.; Libbra, M. V.; Dondi, G.; Pellegrini, E.; Carulli, L.; Galassi, M.; Grassi, Y.; Perticone, F.; Perticone, M.; Battaglia, R.; Filice, M.; Maio, R.; Stanghellini, V.; Ruggeri, E.; del Vecchio, S.; Salvi, A.; Leonardi, R.; Damiani, G.; Capeci, W.; Gabrielli, A.; Mattioli, M.; Martino, G. P.; Biondi, L.; Pettinari, P.; Ghio, R.; Col, A. D.; Minisola, S.; Colangelo, L.; Cilli, M.; Labbadia, G.; Afeltra, A.; Marigliano, B.; Pipita, M. E.; Castellino, P.; Zanoli, L.; Pignataro, S.; Gennaro, A.; Blanco, J.; Saracco, V.; Fogliati, M.; Bussolino, C.; Mete, F.; Gino, M.; Cittadini, A.; Vigorito, C.; Arcopinto, M.; Salzano, A.; Bobbio, E.; Marra, A. M.; Sirico, D.; Moreo, G.; Gasparini, F.; Prolo, S.; Pina, G.; Ballestrero, A.; Ferrando, F.; Berra, S.; Dassi, S.; Nava, M. C.; Graziella, B.; Baldassarre, S.; Fragapani, S.; Gruden, G.; Galanti, G.; Mascherini, G.; Petri, C.; Stefani, L.; Girino, M.; Piccinelli, V.; Nasso, F.; Gioffre, V.; Pasquale, M.; Scattolin, G.; Martinelli, S.; Turrin, M.; Sechi, L.; Catena, C.; Colussi, G.; Passariello, N.; Rin
abstract
In older adults infections are among the leading causes of emergency department visits, hospitalization, morbidity and mortality.
Infections are frequent events diagnosed in older hospitalized patients with a high number of comorbidities and on polypharmacy, respiratory tract infections being the most frequent followed by urinary tract infections
2019
- Prevalence of use and appropriateness of antidepressants prescription in acutely hospitalized elderly patients
[Articolo su rivista]
Carlotta, F.; Raffaella, R.; Ilaria, A.; Alessandro, N.; Mannuccio, M. P.; Mannucci, P. M.; Nobili, A.; Pietrangelo, A.; Perticone, F.; Licata, G.; Violi, F.; Corazza, G. R.; Corrao, S.; Marengoni, A.; Salerno, F.; Cesari, M.; Tettamanti, M.; Pasina, L.; Franchi, C.; Cortesi, L.; Miglio, G.; Ardoino, I.; Novella, A.; Prisco, D.; Silvestri, E.; Emmi, G.; Bettiol, A.; Caterina, C.; Biolo, G.; Zanetti, M.; Guadagni, M.; Zaccari, M.; Chiuch, M.; Vanoli, M.; Grignani, G.; Pulixi, E. A.; Bernardi, M.; Bassi, S. L.; Santi, L.; Zaccherini, G.; Lupattelli, G.; Mannarino, E.; Bianconi, V.; Paciullo, F.; Alcidi, R.; Nuti, R.; Valenti, R.; Ruvio, M.; Cappelli, S.; Palazzuoli, A.; Girelli, D.; Busti, F.; Marchi, G.; Barbagallo, M.; Dominguez, L.; Cocita, F.; Beneduce, V.; Plances, L.; Natoli, G.; Mularo, S.; Raspanti, M.; Cavallaro, F.; Zoli, M.; Lazzari, I.; Brunori, M.; Fabbri, E.; Magalotti, D.; Arno, R.; Pasini, F. L.; Capecchi, P. L.; Palasciano, G.; Modeo, M. E.; Gennaro, C. D.; Cappellini, M. D.; Maira, D.; Di Stefano, V.; Fabio, G.; Seghezzi, S.; Mancarella, M.; De Amicis, M. M.; De Luca, G.; Scaramellini, N.; Rossi, P. D.; Damanti, S.; Clerici, M.; Conti, F.; Bonini, G.; Ottolini, B. B.; Di Sabatino, A.; Miceli, E.; Lenti, M. V.; Pisati, M.; Dominioni, C. C.; Murialdo, G.; Marra, A.; Cattaneo, F.; Pontremoli, R.; Beccati, V.; Nobili, G.; Secchi, M. B.; Ghelfi, D.; Anastasio, L.; Sofia, L.; Carbone, M.; Cipollone, F.; Guagnano, M. T.; Valeriani, E.; Rossi, I.; Mancuso, G.; Calipari, D.; Bartone, M.; Delitala, G.; Berria, M.; Pes, C.; Delitala, A.; Muscaritoli, M.; Molfino, A.; Petrillo, E.; Zuccala, G.; D'Aurizio, G.; Romanelli, G.; Zucchelli, A.; Manzoni, F.; Volpini, A.; Picardi, A.; Gentilucci, U. V.; Gallo, P.; Dell'Unto, C.; Annoni, G.; Corsi, M.; Bellelli, G.; Zazzetta, S.; Mazzola, P.; Szabo, H.; Bonfanti, A.; Arturi, F.; Succurro, E.; Rubino, M.; Tassone, B.; Sesti, G.; Interna, M.; Serra, M. G.; Bleve, M. A.; Gasbarrone, L.; Sajeva, M. R.; Brucato, A.; Ghidoni, S.; Fabris, F.; Bertozzi, I.; Bogoni, G.; Rabuini, M. V.; Cosi, E.; Scarinzi, P.; Amabile, A.; Omenetto, E.; Prandini, T.; Manfredini, R.; Fabbian, F.; Boari, B.; Giorgi, A. D.; Tiseo, R.; De Giorgio, R.; Paolisso, G.; Rizzo, M. R.; Borghi, C.; Strocchi, E.; Ianniello, E.; Soldati, M.; Sabba, C.; Vella, F. S.; Suppressa, P.; Schilardi, A.; Loparco, F.; De Vincenzo, G. M.; Comitangelo, A.; Amoruso, E.; Fenoglio, L.; Falcetta, A.; Bracco, C.; Fracanzani, A. L.; Fargion, S.; Tiraboschi, S.; Cespiati, A.; Oberti, G.; Sigon, G.; Peyvandi, F.; Rossio, R.; Ferrari, B.; Colombo, G.; Agosti, P.; Monzani, V.; Savojardo, V.; Folli, C.; Ceriani, G.; Pallini, G.; Dallegri, F.; Ottonello, L.; Liberale, L.; Caserza, L.; Salam, K.; Liberato, N. L.; Tognin, T.; Bianchi, G. B.; Giaquinto, S.; Purrello, F.; Di Pino, A.; Piro, S.; Rozzini, R.; Falanga, L.; Spazzini, E.; Ferrandina, C.; Montrucchio, G.; Petitti, P.; Peasso, P.; Favale, E.; Poletto, C.; Salmi, Rudy; Gaudenzi, P.; Perri, L.; Landolfi, R.; Montalto, M.; Mirijello, A.; Guasti, L.; Castiglioni, L.; Maresca, A.; Squizzato, A.; Campiotti, L.; Grossi, A.; Bertolotti, M.; Mussi, C.; Lancellotti, G.; Libbra, M. V.; Dondi, G.; Pellegrini, E.; Carulli, L.; Galassi, M.; Grassi, Y.; Perticone, M.; Battaglia, R.; Filice, M.; Maio, R.; Stanghellini, V.; Ruggeri, E.; del Vecchio, S.; Salvi, A.; Leonardi, R.; Damiani, G.; Capeci, W.; Gabrielli, A.; Mattioli, M.; Martino, G. P.; Biondi, L.; Pettinari, P.; Ghio, R.; Col, A. D.; Minisola, S.; Colangelo, L.; Cilli, M.; Labbadia, G.; Afeltra, A.; Marigliano, B.; Pipita, M. E.; Castellino, P.; Zanoli, L.; Pignataro, S.; Gennaro, A.; Blanco, J.; Saracco, V.; Fogliati, M.; Bussolino, C.; Mete, F.; Gino, M.; Cittadini, A.; Vigorito, C.; Arcopinto, M.; Salzano, A.; Bobbio, E.; Marra, A. M.; Sirico, D.; Moreo, G.; Gasparini, F.; Prolo, S.; Pina, G.; Ballestrero, A.; Ferrando, F.; Berra, S.; Dassi, S.; Nava, M. C.; Graziella, B.; Baldassarre, S.; Fragapani, S.; Gruden, G.; Galanti, G.; Mascherini, G
abstract
N/A
2018
- Appropriateness of oral anticoagulant therapy prescription and its associated factors in hospitalized older people with atrial fibrillation
[Articolo su rivista]
Franchi, Carlotta; Antoniazzi, Stefania; Proietti, Marco; Nobili, Alessandro; Mannucci, Pier Mannuccio; Santalucia, Paola; Monzani, Valter; Marcucci, Maura; Antoniazzi, Stefania; Bosari, Silvano; Mannucci, Pier Mannuccio; Franchi, Carlotta; Brignolo, Barbara; Proietti, Marco; Nicolis, Enrico; Ardoino, Ilaria; Fenoglio, Luigi M.; Melchio, Remo; Fabris, Fabrizio; Sartori, Maria Teresa; Manfredini, Roberto; De Giorgi, Alfredo; Fabbian, Fabio; Biolo, Gianni; Zanetti, Michela; Altamura, Nicola; Sabbà, Carlo; Suppressa, Patrizia; Bandiera, Francesco; Usai, Carlo; Murialdo, Giovanni; Fezza, Francesca; Marra, Alessio; Castelli, Francesca; Cattaneo, Federico; Beccati, Valentina; di Minno, Giovanni; Tufano, Antonella; Contaldi, Paola; Lupattelli, Graziana; Bianconi, Vanessa; Cappellini, Domenica; Hu, Cinzia; Minonzio, Francesca; Fargion, Silvia; Burdick, Larry; Francione, Paolo; Peyvandi, Flora; Rossio, Raffaella; Colombo, Giulia; Ceriani, Giuliana; Lucchi, Tiziano; Manfellotto, Dario; Caridi, Irene; Corazza, Gino Roberto; Miceli, Emanuela; Padula, Donatella; Fraternale, Giacomo; Guasti, Luigina; Squizzato, Alessandro; Maresca, Andrea; Liberato, Nicola Lucio; Tognin, Tiziana; Rozzini, Renzo; Bellucci, Francesco Baffa; Muscaritoli, Maurizio; Molfino, Alessio; Petrillo, Enrico; Dore, Maurizio; Mete, Francesca; Gino, Miriam; Franceschi, Francesco; Gabrielli, Maurizio; Perticone, Francesco; Perticone, Maria; Bertolotti, Marco; Mussi, Chiara; Borghi, Claudio; Strocchi, Enrico; Durazzo, Marilena; Fornengo, Paolo; Dallegri, Franco; Ottonello, Luciano Carlo; Salam, Kassem; Caserza, Lara; Barbagallo, Mario; Di Bella, Giovanna; Annoni, Giorgio; Bruni, Adriana Antonella; Odetti, Patrizio; Nencioni, Alessio; Monacelli, Fiammetta; Napolitano, Armando; Brucato, Antonio; Valenti, Anna; Castellino, Pietro; Zanoli, Luca; Mazzeo, Marco
abstract
Aims: Although oral anticoagulants (OACs) are effective in preventing stroke in older people with atrial fibrillation (AF), they are often underused in this particularly high-risk population. The aim of the present study was to assess the appropriateness of OAC prescription and its associated factors in hospitalized patients aged 65 years or older. Methods: Data were obtained from the retrospective phase of Simulation-based Technologies to Improve the Appropriate Use of Oral Anticoagulants in Hospitalized Elderly Patients With Atrial Fibrillation (SIM-AF) study, held in 32 Italian internal medicine and geriatric wards. The appropriateness of OAC prescription was assessed, grouping patients in those who were and were not prescribed OACs at hospital discharge. Multivariable logistic regression was used to establish factors independently associated with the appropriateness of OAC prescription. Results: A total of 328 patients were included in the retrospective phase of the study. Of these, almost 44% (N = 143) were inappropriately prescribed OACs, being mainly underprescribed or prescribed an inappropriate antithrombotic drug (N = 88). Among the patients prescribed OACs (N = 221), errors in the prescribed doses were the most frequent cause of inappropriate use (N = 55). Factors associated with a higher degree of patient frailty were inversely associated with the appropriateness of OAC prescription. Conclusions: In hospitalized older patients with AF, there is still a high prevalence of inappropriate OAC prescribing. Characteristics usually related to frailty are associated with the inappropriate prescribing. These findings point to the need for targeted interventions designed for internists and geriatricians, aimed at improving the appropriate prescribing of OACs in this complex and high-risk population.
2018
- Choice and Outcomes of Rate Control versus Rhythm Control in Elderly Patients with Atrial Fibrillation: A Report from the REPOSI Study
[Articolo su rivista]
Paciullo, Francesco; Proietti, Marco; Bianconi, Vanessa; Nobili, Alessandro; Pirro, Matteo; Mannucci, Pier Mannuccio; Lip, Gregory Y. H.; Lupattelli, Graziana; Tettamanti, Mauro; Pasina, Luca; Franchi, Carlotta; Perticone, Francesco; Salerno, Francesco; Corrao, Salvatore; Marengoni, Alessandra; Licata, Giuseppe; Violi, Francesco; Corazza, Gino Roberto; Marcucci, Maura; Eldin, Tarek Kamal; Di Blanca, Maria Pia Donatella; Lanzo, Giovanna; Astuto, Sarah; Ardoino, Ilaria; Cortesi, Laura; Prisco, Domenico; Silvestri, Elena; Cenci, Caterina; Emmi, Giacomo; Biolo, Gianni; Guarnieri, Gianfranco; Zanetti, Michela; Fernandes, Giovanni; Chiuch, Massimiliano; Vanoli, Massimo; Grignani, Giulia; Casella, Gianluca; Pulixi, Edoardo Alessandro; Bernardi, Mauro; Bassi, Silvia Li; Santi, Luca; Zaccherini, Giacomo; Mannarino, Elmo; Nuti, Ranuccio; Valenti, Roberto; Ruvio, Martina; Cappelli, Silvia; Palazzuoli, Alberto; Salvatore, Teresa; Sasso, Ferdinando Carlo; Girelli, Domenico; Olivieri, Oliviero; Matteazzi, Thomas; Barbagallo, Mario; Plances, Lidia; Alcamo, Roberta; Calvo, Luigi; Valenti, Maria; Zoli, Marco; Arnò, Raffaella; Pasini, Franco Laghi; Capecchi, Pier Leopoldo; Bicchi, Maurizio; Palasciano, Giuseppe; Modeo, Maria Ester; Peragine, Maria; Pappagallo, Fabrizio; Pugliese, Stefania; Di Gennaro, Carla; Postiglione, Alfredo; Barbella, Maria Rosaria; De Stefano, Francesco; Cappellini, MARIA DOMENICA; Fabio, Giovanna; Seghezzi, Sonia; De Amicis, Margherita Migone; Mancarella, Marta; Mari, Daniela; Rossi, Paolo Dionigi; Damanti, Sarah; Ottolini, Barbara Brignolo; Bonini, Giulia; Miceli, Emanuela; Lenti, Marco Vincenzo; Padula, Donatella; Murialdo, Giovanni; Marra, GIUSEPPE ALESSIO; Cattaneo, Federico; Secchi, Maria Beatrice; Ghelfi, Davide; Anastasio, Luigi; Sofia, Lucia; Carbone, Maria Maddalena; Davì, Giovanni; Guagnano, Maria Teresa; Sestili, Simona; Mancuso, Gerardo; Calipari, Daniela; Bartone, Mosè; Meroni, Maria Rachele; Perin, Paolo Cavallo; Lorenzati, Bartolomeo; Gruden, Gabriella; Bruno, Graziella; Amione, Cristina; Fornengo, Paolo; Tassara, Rodolfo; Melis, Deborah; Rebella, Lara; Delitala, Giuseppe; Pretti, Vincenzo; Masala, Maristella Salvatora; Pes, Chiara; Bolondi, Luigi; Rasciti, Leonardo; Serio, Ilaria; Fanelli, Filippo Rossi; Amoroso, Antonio; Molfino, Alessio; Petrillo, Enrico; Zuccalà, Giuseppe; Franceschi, Francesco; De Marco, Guido; Chiara, Cordischi; Marta, Sabbatini; D’Aurizio, Gabriella; Romanelli, Giuseppe; Amolini, Claudia; Chiesa, Deborah; Picardi, Antonio; Gentilucci, Umberto Vespasiani; Gallo, Paolo; Annoni, Giorgio; Corsi, Maurizio; Zazzetta, Sara; Bellelli, Giuseppe; Szabo, Hajnalka; Arturi, Franco; Succurro, Elena; Rubino, Mariangela; Sesti, Giorgio; Loria, Paola; Becchi, Maria Angela; Martucci, Gianfranco; Fantuzzi, Alessandra; Maurantonio, Mauro; Serra, Maria Grazia; Bleve, Maria Antonietta; Gasbarrone, Laura; Sajeva, Maria Rosaria; Brucato, Antonio; Ghidoni, Silvia; Di Corato, Paola; Agnelli, Giancarlo; Marchesini, Emanuela; Fabris, Fabrizio; Carlon, Michela; Turatto, Francesca; Baritusso, Aldo; Amabile, Annalisa; Omenetto, Elisabetta; Scarinzi, Paolo; Manfredini, Roberto; Molino, Christian; Pala, Marco; Fabbian, Fabio; Boari, Benedetta; De Giorgi, Alfredo; Paolisso, Giuseppe; Rizzo, Maria Rosaria; Laieta, Maria Teresa; Rini, Giovanbattista; Mansueto, Pasquale; Pepe, Ilenia; Borghi, Claudio; Strocchi, Enrico; De Sando, Valeria; Pareo, Ilaria; Sabbà, Carlo; Vella, Francesco Saverio; Suppressa, Patrizia; Valerio, Raffaella; Agosti, Pasquale; Fontana, Flavia; Loparco, Francesca; Capobianco, Caterina; Fenoglio, Luigi; Bracco, Christian; Giraudo, Alessia Valentina; Testa, Elisa; Serraino, Cristina; Fargion, Silvia; Bonara, Paola; Periti, Giulia; Porzio, Marianna; Tiraboschi, Slivia; Peyvandi, Flora; Tedeschi, Alberto; Rossio, Raffaella; Ferrari, Barbara; Monzani, Valter; Savojardo, Valeria; Folli, Christian; Magnini, Maria; Conca, Alessio; Gobbo, Giulia; Pallini, G
abstract
Background: Among rate-control or rhythm-control strategies, there is conflicting evidence as to which is the best management approach for non-valvular atrial fibrillation (AF) in elderly patients. Design: We performed an ancillary analysis from the ‘Registro Politerapie SIMI’ study, enrolling elderly inpatients from internal medicine and geriatric wards. Methods: We considered patients enrolled from 2008 to 2014 with an AF diagnosis at admission, treated with a rate-control-only or rhythm-control-only strategy. Results: Among 1114 patients, 241 (21.6%) were managed with observation only and 122 (11%) were managed with both the rate- and rhythm-control approaches. Of the remaining 751 patients, 626 (83.4%) were managed with a rate-control-only strategy and 125 (16.6%) were managed with a rhythm-control-only strategy. Rate-control-managed patients were older (p = 0.002), had a higher Short Blessed Test (SBT; p = 0.022) and a lower Barthel Index (p = 0.047). Polypharmacy (p = 0.001), heart failure (p = 0.005) and diabetes (p = 0.016) were more prevalent among these patients. Median CHA2DS2-VASc score was higher among rate-control-managed patients (p = 0.001). SBT [odds ratio (OR) 0.97, 95% confidence interval (CI) 0.94–1.00, p = 0.037], diabetes (OR 0.48, 95% CI 0.26–0.87, p = 0.016) and polypharmacy (OR 0.58, 95% CI 0.34–0.99, p = 0.045) were negatively associated with a rhythm-control strategy. At follow-up, no difference was found between rate- and rhythm-control strategies for cardiovascular (CV) and all-cause deaths (6.1 vs. 5.6%, p = 0.89; and 15.9 vs. 14.1%, p = 0.70, respectively). Conclusion: A rate-control strategy is the most widely used among elderly AF patients with multiple comorbidities and polypharmacy. No differences were evident in CV death and all-cause death at follow-up.
2018
- Correction to: Major adverse cardiovascular events in non-valvular atrial fibrillation with chronic obstructive pulmonary disease: the ARAPACIS study (Internal and Emergency Medicine, (2018), 13, 5, (651-660), 10.1007/s11739-018-1835-9)
[Articolo su rivista]
Raparelli, Valeria; Pastori, Daniele; Pignataro, Serena Francesca; Vestri, Anna Rita; Pignatelli, Pasquale; Cangemi, Roberto; Proietti, Marco; Davì, Giovanni; Hiatt, William Robert; Lip, Gregory Yoke Hong; Corazza, Gino Roberto; Perticone, Francesco; Violi, Francesco; Basili, Stefania; Alessandri, C.; Serviddio, G.; Palange, P.; Greco, E.; Bruno, G.; Averna, M.; Giammanco, A.; Sposito, P.; De Cristofaro, R.; Carulli, L.; Di Gennaro, L.; Pellegrini, E.; Cominacini, L.; Mozzini, C.; Pasini, A. F.; Sprovieri, M.; Spagnuolo, V.; Cerqua, G.; Cerasola, G.; Mulé, G.; Barbagallo, M.; Lo Sciuto, S.; Monteverde, A.; Saitta, A.; Lo Gullo, A.; Malatino, L.; Cilia, C.; Terranova, V.; Pisano, M.; Pinto, A.; Di Raimondo, D.; Tuttolomondo, A.; Conigliaro, R.; Signorelli, S.; De Palma, D.; Galderisi, M.; Cudemo, G.; Galletti, F.; Fazio, V.; De Luca, N.; Meccariello, A.; Caputo, D.; De Donato, M. T.; Iannuzi, A.; Bresciani, A.; Giunta, R.; Utili, R.; Iorio, V.; Adinolfi, L. E.; Sellitto, C.; Iuliano, N.; Bellis, P.; Tirelli, P.; Sacerdoti, D.; Vanni, D.; Iuliano, L.; Ciacciarelli, M.; Pacelli, A.; Palazzuoli, A.; Cacciafesta, M.; Gueli, N.; Lo Iacono, C.; Brusco, S.; Verrusio, W.; Nobili, L.; Tarquinio, N.; Pellegrini, F.; Vincentelli, G. M.; Ravallese, F.; Santini, C.; Letizia, C.; Petramala, L.; Zinnamosca, L.; Minisola, S.; Cilli, M.; Colangelo, L.; Falaschi, P.; Martocchia, A.; Pastore, F.; Bertazzoni, G.; Attalla El Halabieh, E.; Paradiso, Maria Bruna; Lizzi, E. M.; Timmi, S.; Battisti, P.; Cerci, S.; Ciavolella, M.; Di Veroli, C.; Malci, F.; De Ciocchis, A.; Abate, D.; Castellino, P.; Zanoli, L.; Fidone, F.; Mannarino, E.; Pasqualini, L.; Oliverio, G.; Pende, A.; Artom, N.; Ricchio, R.; Fimognari, F. L.; Alletto, M.; Messina, S.; Sesti, G.; Arturi, F.; Succurro, E.; Fiorentino, T. V.; Pedace, E.; Scarpino, P. E.; Carullo, G.; Maio, R.; Sciacqua, A.; Frugiuele, P.; Spagnuolo, V.; Battaglia, G.; Atzori, S.; Delitala, G.; Angelucci, E.; Sestili, S.; Traisci, G.; De Feudis, L.; Di Michele, D.; Fava, A.; Balsano, C.; De Ciantis, P.; Desideri, G.; Camerota, A.; Mezzetti, M.; Gresele, P.; Vedovati, C.; Fierro, T.; Puccetti, L.; Bertolotti, M.; Mussi, C.; Boddi, M.; Savino, A.; Contri, S.; Degl’Innocenti, G.; Saller, A.; Fabris, F.; Pesavento, R.; Filippi, L.; Vedovetto, V.; Puato, M.; Fabris, F.; Treleani, M.; De Luca, E.; De Zaiacomo, F.; Giantin, V.; Semplicini, A.; Minuz, P.; Romano, S.; Fantin, F.; Manica, A.; Stockner, I.; Pattis, P.; Gutmann, B.; Catena, Chiara; Colussi, G.; Sechi, L. A.; Annoni, G.; Bruni, A. A.; Castagna, A.; Spinelli, D.; Miceli, E.; Padula, D.; Schinco, G.; Spreafico, S.; Secchi, B.; Vanoli, M.; Casella, G.; Pulixi, E. A.; Sansone, L.; Serra, M. G.; Longo, S.; Antonaci, S.; Belfiore, A.; Frualdo, M.; Palasciano, G.; Ricci, L.; Ventrella, F.; Bianco, C.; Santovito, D.; Cipollone, F.; Nicolai, S.; Salvati, F.; Rini, G. B.; Scozzari, F.; Muiesan, M. L.; Salvetti, M.; Bazza, A.; Picardi, A.; Vespasiani-Gentilucci, U.; De Vincentis, Alessia; Cosio, P.; Terzolo, M.; Madaffari, B.; Parasporo, B.; Fenoglio, L.; Bracco, C.; Melchio, R.; Gentili, T.; Salvi, A.; Nitti, C.; Gabrielli, A.; Martino, G. P.; Capucci, A.; Brambatti, M.; Sparagna, A.; Tirotta, D.; Andreozzi, P.; Ettorre, E.; Viscogliosi, G.; Servello, A.; Musumeci, M.; Delfino, M.; Giorgi, A.; Glorioso, N.; Melis, G.; Marras, G.; Matta, M.; Sacco, A.; Stellitano, E.; Scordo, A.; Russo, F.; Caruso, A. A.; Porreca, E.; Tana, M.; Ferri, C.; Cheli, P.; Portincasa, P.; Muscianisi, G.; Giordani, S.; Stanghellini, V.; Sabbà, C.; Mancuso, G.; Bartone, M.; Calipari, D.; Arcidiacono, G.; Bellanuova, I.; Ferraro, M.; Marigliano, G.; Cozzolino, D.; Lampitella, A.; Acri, V.; Galasso, D.; Mazzei, F.; Buratti, A.; Galasso, S.; Porta, M.; Brizzi, M. F.; Fattorini, A.; Sampietro, F.; D’Angelo, A.; Manfredini, R.; Pala, M.; Fabbian, F.; Moroni, C.; Valente, L.; Lopreiato, F.
abstract
In the original publication, one of the ARAPACIS collaborators Dr. “Leonardo Di Gennaro” name has been erroneously mentioned as “Leonardo De Gennaro”.
2018
- Executive Summary of the 2018 Joint Consensus Document on Cardiovascular Disease Prevention in Italy
[Articolo su rivista]
Volpe, Massimo; Battistoni, Allegra; Gallo, Giovanna; Rubattu, Speranza; Tocci, Giuliano; Accettura, Domenico; Bellone, Simonetta; Bellotti, Paolo; Bertolotti, Marco; Borghi, Claudio; Casasco, Maurizio; Consoli, Agostino; Coppini, Rafaele; Corsini, Alberto; Costanzo, Gianfranco; Desideri, Giovambattista; Ferri, Claudio; Galanti, Giorgio; Giada, Franco; Icardi, Giancarlo; Lombardi, Niccolò; Modena, Maria Grazia; Modesti, Pietro Amedeo; Monti, Giorgio; Mugelli, Alessandro; Orsi, Andrea; Parati, Gianfranco; Pedretti, Roberto F. E.; Perseghin, Gianluca; Pirro, Matteo; Ricotti, Roberta; Rizzoni, Damiano; Rotella, Carlo; Salvetti, Guido; Sarto, Patrizio; Tassinari, Federico; Trimarco, Bruno; de Kreutzenberg, Saula Vigili; Volpe, Roberto
abstract
Cardiovascular diseases (CVDs) are the leading cause of death, disability and hospitalization in Italy. Primary prevention strategies are able to prevent clinically evident CVDs, mostly by early identifying asymptomatic, otherwise healthy individuals at risk of developing CVDs. A more modern approach recommended for effective CVD prevention is based on “4P”, that is: Predictive, Preventive, Personalized and Participative. This executive document reflects the key points of a consensus paper on CV prevention in Italy, realized though the contribution of different Italian Scientific Societies and the National Research Council, and coordinated by the Italian Society of Cardiovascular Prevention (SIPREC), published in 2018. The need for such document relies on the difficulty to apply “sic et simpliciter” European guidelines, to which this document is largely inspired, to national, regional and local realities, in this Mediterranean country, namely Italy. Indeed, our Country has specific features in terms of demography, socio-cultural habits, distribution and prevalence of risk factors, organization, policy and access to National Health Service compared to other European countries.
2018
- Implementation of the Frailty Index in hospitalized older patients: Results from the REPOSI register
[Articolo su rivista]
Cesari, M.; Franchi, C.; Cortesi, L.; Nobili, A.; Ardoino, I.; Mannucci, P. M.; Tettamanti, M.; Pasina, L.; Perticone, F.; Salerno, F.; Corrao, S.; Marengoni, A.; Licata, G.; Violi, F.; Corazza, G. R.; Eldin, T. K.; Di Blanca, M. P. D.; Lanzo, G.; Astuto, S.; Prisco, D.; Silvestri, E.; Cenci, C.; Emmi, G.; Biolo, G.; Guarnieri, G.; Zanetti, M.; Fernandes, G.; Chiuch, M.; Vanoli, M.; Grignani, G.; Casella, G.; Pulixi, E. A.; Bernardi, M.; Bassi, S. L.; Santi, L.; Zaccherini, G.; Mannarino, E.; Lupattelli, G.; Bianconi, V.; Paciullo, F.; Nuti, R.; Valenti, R.; Ruvio, M.; Cappelli, S.; Palazzuoli, A.; Salvatore, T.; Sasso, F. C.; Girelli, D.; Olivieri, O.; Matteazzi, T.; Barbagallo, M.; Plances, L.; Alcamo, R.; Calvo, L.; Valenti, M.; Zoli, M.; Arno, R.; Pasini, F. L.; Capecchi, P. L.; Bicchi, M.; Palasciano, G.; Modeo, M. E.; Peragine, M.; Pappagallo, F.; Pugliese, S.; Gennaro, C. D.; Postiglione, A.; Barbella, M. R.; De Stefano, F.; Cappellini, M. D.; Fabio, G.; Seghezzi, S.; De Amicis, M. M.; Mancarella, M.; Mari, D.; Rossi, P. D.; Damanti, S.; Ottolini, B. B.; Bonini, G.; Miceli, E.; Lenti, M. V.; Padula, D.; Murialdo, G.; Marra, A.; Cattaneo, F.; Secchi, M. B.; Ghelfi, D.; Anastasio, L.; Sofia, L.; Carbone, M.; Davi, G.; Guagnano, M. T.; Sestili, S.; Mancuso, G.; Calipari, D.; Bartone, M.; Meroni, M. R.; Perin, P. C.; Lorenzati, B.; Gruden, G.; Bruno, G.; Amione, C.; Fornengo, P.; Tassara, R.; Melis, D.; Rebella, L.; Delitala, G.; Pretti, V.; Masala, M. S.; Pes, C.; Bolondi, L.; Rasciti, L.; Serio, I.; Fanelli, F. R.; Amoroso, A.; Molfino, A.; Petrillo, E.; Zuccala, G.; Franceschi, F.; De Marco, G.; Chiara, C.; Marta, S.; D'aurizio, G.; Romanelli, G.; Amolini, C.; Chiesa, D.; Picardi, A.; Gentilucci, U. V.; Gallo, P.; Annoni, G.; Corsi, M.; Zazzetta, S.; Bellelli, G.; Szabo, H.; Arturi, F.; Succurro, E.; Rubino, M.; Sesti, G.; Loria, P.; Becchi, M. A.; Martucci, G.; Fantuzzi, A.; Maurantonio, M.; Serra, M. G.; Bleve, M. A.; Gasbarrone, L.; Sajeva, M. R.; Brucato, A.; Ghidoni, S.; Di Corato, P.; Agnelli, G.; Marchesini, E.; Fabris, F.; Carlon, M.; Turatto, F.; Baritusso, A.; Amabile, A.; Omenetto, E.; Scarinzi, P.; Manfredini, R.; Molino, C.; Pala, M.; Fabbian, F.; Boari, B.; De Giorgi, A.; Paolisso, G.; Rizzo, M. R.; Laieta, M. T.; Rini, G.; Mansueto, P.; Pepe, I.; Borghi, C.; Strocchi, E.; De Sando, V.; Pareo, I.; Sabba, C.; Vella, F. S.; Suppressa, P.; Valerio, R.; Agosti, P.; Fontana, F.; Loparco, F.; Capobianco, C.; Fenoglio, L.; Bracco, C.; Giraudo, A. V.; Testa, E.; Serraino, C.; Fargion, S.; Bonara, P.; Periti, G.; Porzio, M.; Tiraboschi, S.; Peyvandi, F.; Tedeschi, A.; Rossio, R.; Monzani, V.; Savojardo, V.; Folli, C.; Magnini, M.; Conca, A.; Gobbo, G.; Pallini, G.; Valenti, M.; Balduini, C. L.; Bertolino, G.; Provini, S.; Quaglia, F.; Dallegri, F.; Ottonello, L.; Liberale, L.; Chin, W. S.; Carassale, L.; Caporotundo, S.; Traisci, G.; De Feudis, L.; Di Carlo, S.; Liberato, N. L.; Buratti, A.; Tognin, T.; Bianchi, G. B.; Giaquinto, S.; Purrello, F.; Di Pino, A.; Piro, S.; Rozzini, R.; Falanga, L.; Spazzini, E.; Montrucchio, G.; Greco, E.; Tizzani, P.; Petitti, P.; Perciccante, A.; Coralli, A.; Salmi, R.; Gaudenzi, P.; Gamberini, S.; Semplicini, A.; Gottardo, L.; Vendemiale, G.; Serviddio, G.; Forlano, R.; Masala, C.; Mammarella, A.; Raparelli, V.; Basili, S.; Perri, L.; Landolfi, R.; Montalto, M.; Mirijello, A.; Vallone, C.; Bellusci, M.; Setti, D.; Pedrazzoli, F.; Guasti, L.; Castiglioni, L.; Maresca, A.; Squizzato, A.; Molaro, M.; Bertolotti, M.; Mussi, C.; Libbra, M. V.; Miceli, A.; Pellegrini, E.; Carulli, L.; Veltri, F.; Sciacqua, A.; Quero, M.; Bagnato, C.; Colangelo, L.; Falbo, T.; De Giorgio, R.; Serra, M.; Grasso, V.; Ruggeri, E.; Ilaria, B.; Salvi, A.; Leonardi, R.; Grassini, C.; Mascherona, I.; Minelli, G.; Maltese, F.; Damiani, G.; Capeci, W.; Mattioli, M.; Martino, G. P.; Biondi, L.; Ormas, M.; Pettinari, P.; Romiti, R.; Messina, S.; Cavallaro, F.; Ghio, R.; Favorini, S.; Col, A. D.; Minisola, S.; Colange
abstract
Background: Frailty is a state of increased vulnerability to stressors, associated to poor health outcomes. The aim of this study was to design and introduce a Frailty Index (FI; according to the age-related accumulation of deficit model) in a large cohort of hospitalized older persons, in order to benefit from its capacity to comprehensively weight the risk profile of the individual. Methods: Patients aged 65 and older enrolled in the REPOSI register from 2010 to 2016 were considered in the present analyses. Variables recorded at the hospital admission (including socio-demographic, physical, cognitive, functional and clinical factors) were used to compute the FI. The prognostic impact of the FI on in-hospital and 12-month mortality was assessed. Results: Among the 4488 patients of the REPOSI register, 3847 were considered eligible for a 34-item FI computation. The median FI in the sample was 0.27 (interquartile range 0.21–0.37). The FI was significantly predictive of both in-hospital (OR 1.61, 95%CI 1.38–1.87) and overall (HR 1.46, 95%CI 1.32–1.62) mortality, also after adjustment for age and sex. Conclusions: The FI confirms its strong predictive value for negative outcomes. Its implementation in cohort studies (including those conducted in the hospital setting) may provide useful information for better weighting the complexity of the older person and accordingly design personalized interventions.
2018
- Integrated assessment of global cardiovascular risk, risk maps and their use in clinical practice
[Articolo su rivista]
Pirro, M.; Bertolotti, M.
abstract
2018
- Living alone as an independent predictor of prolonged length of hospital stay and non-home discharge in older patients
[Articolo su rivista]
Agosti, P.; Tettamanti, M.; Vella, F. S.; Suppressa, P.; Pasina, L.; Franchi, C.; Nobili, A.; Mannucci, P. M.; Sabba, C.; Corrao, S.; Marengoni, A.; Marcucci, M.; Salerno, F.; Perticone, F.; Licata, G.; Violi, F.; Corazza, G. R.; Cortesi, L.; Ardoino, I.; Prisco, D.; Silvestri, E.; Cenci, C.; Emmi, G.; Biolo, G.; Zanetti, M.; Guadagni, M.; Zaccari, M.; Vanoli, M.; Grignani, G.; Pulixi, E. A.; Bernardi, M.; Bassi, S. L.; Santi, L.; Zaccherini, G.; Mannarino, E.; Lupattelli, G.; Bianconi, V.; Paciullo, F.; Nuti, R.; Valenti, R.; Ruvio, M.; Cappelli, S.; Palazzuoli, A.; Olivieri, O.; Girelli, D.; Matteazzi, T.; Barbagallo, M.; Dominguez, L.; Cocita, F.; Beneduce, V.; Plances, L.; Zoli, M.; Lazzari, I.; Brunori, M.; Pasini, F. L.; Capecchi, P. L.; Palasciano, G.; Modeo, M. E.; Di Gennaro, C.; Cappellini, M. D.; Maira, D.; Di Stefano, V.; Fabio, G.; Seghezzi, S.; Mancarella, M.; Cesari, M.; Rossi, P. D.; Damanti, S.; Clerici, M.; Conti, F.; Miceli, E.; Lenti, M. V.; Pisati, M.; Dominioni, C. C.; Murialdo, G.; Marra, A.; Cattaneo, F.; Secchi, M. B.; Ghelfi, D.; Anastasio, L.; Sofia, L.; Carbone, M.; Cipollone, F.; Guagnano, M. T.; Angelucci, E.; Valeriani, E.; Mancuso, G.; Calipari, D.; Bartone, M.; Delitala, G.; Berria, M.; Muscaritoli, M.; Molfino, A.; Petrillo, E.; Zuccala, G.; D'aurizio, G.; Romanelli, G.; Zucchelli, A.; Picardi, A.; Gentilucci, U. V.; Gallo, P.; Dell'unto, C.; Annoni, G.; Corsi, M.; Bellelli, G.; Zazzetta, S.; Mazzola, P.; Szabo, H.; Bonfanti, A.; Arturi, F.; Succurro, E.; Rubino, M.; Serra, M. G.; Bleve, M. A.; Gasbarrone, L.; Sajeva, M. R.; Brucato, A.; Ghidoni, S.; Fabris, F.; Bertozzi, I.; Bogoni, G.; Rabuini, M. V.; Cosi, E.; Manfredini, R.; Fabbian, F.; Boari, B.; De Giorgi, A.; Tiseo, R.; Paolisso, G.; Rizzo, M. R.; Borghi, C.; Strocchi, E.; De Sando, V.; Pareo, I.; Schilardi, A.; Loparco, F.; Fenoglio, L.; Bracco, C.; Giraudo, A. V.; Fargion, S.; Periti, G.; Porzio, M.; Tiraboschi, S.; Peyvandi, F.; Rossio, R.; Ferrari, B.; Colombo, G.; Monzani, V.; Savojardo, V.; Folli, C.; Ceriani, G.; Pallini, G.; Dallegri, F.; Ottonello, L.; Liberale, L.; Caserza, L.; Salam, K.; Liberato, N. L.; Tognin, T.; Bianchi, G. B.; Giaquinto, S.; Purrello, F.; Di Pino, A.; Piro, S.; Rozzini, R.; Falanga, L.; Spazzini, E.; Ferrandina, C.; Montrucchio, G.; Petitti, P.; Salmi, R.; Gaudenzi, P.; Perri, L.; Landolfi, R.; Montalto, M.; Mirijello, A.; Guasti, L.; Castiglioni, L.; Maresca, A.; Squizzato, A.; Molaro, M.; Grossi, A.; Bertolotti, M.; Mussi, C.; Libbra, M. V.; Dondi, G.; Pellegrini, E.; Carulli, L.; Colangelo, L.; Falbo, T.; Stanghellini, V.; De Giorgio, R.; Ruggeri, E.; Del Vecchio, S.; Salvi, A.; Leonardi, R.; Damiani, G.; Gabrielli, A.; Capeci, W.; Mattioli, M.; Martino, G. P.; Biondi, L.; Pettinari, P.; Ghio, R.; Dal Col, A.; Minisola, S.; Colangelo, L.; Afeltra, A.; Marigliano, B.; Pipita, M. E.; Castellino, P.; Blanco, J.; Zanoli, L.; Pignataro, S.; Saracco, V.; Fogliati, M.; Bussolino, C.; Mete, F.; Gino, M.; Cittadini, A.; Vigorito, C.; Arcopinto, M.; Salzano, A.; Bobbio, E.; Marra, A. M.; Sirico, D.; Moreo, G.; Gasparini, F.; Prolo, S.; Pina, G.; Ballestrero, A.; Ferrando, F.; Berra, S.; Dassi, S.; Nava, M. C.; Graziella, B.; Baldassarre, S.; Fragapani, S.; Gruden, G.; Galanti, G.; Mascherini, G.; Petri, C.; Stefani, L.; Girino, M.; Piccinelli, V.; Nasso, F.; Gioffre, V.; Pasquale, M.; Scattolin, G.; Martinelli, S.; Turrin, M.; Sechi, L.; Catena, C.; Colussi, G.; Passariello, N.; Rinaldi, L.; Berti, F.; Famularo, G.; Patrizia, T.; Castello, R.; Pasino, M.; Ceda, G. P.; Maggio, M. G.; Morganti, S.; Artoni, A.; Del Giacco, S.; Firinu, D.; Losa, F.; Paoletti, G.; Montalto, G.; Licata, A.; Malerba, V.; Antonino, L.; Basile, G.; Catalano, A.; Malatino, L.; Stancanelli, B.; Terranova, V.; Di Marca, S.; Mecocci, P.; Ruggiero, C.; Boccardi, V.; Meschi, T.; Lauretani, F.; Ticinesi, A.; Minuz, P.; Fondrieschi, L.; Pirisi, M.; Fra, G. P.; Sola, D.; Porta, M.; Riva, P.; Quadri, R.; Scanzi, G.; Mengoli, C.; Provini, S.; Ric
abstract
2018
- Major adverse cardiovascular events in non-valvular atrial fibrillation with chronic obstructive pulmonary disease: the ARAPACIS study
[Articolo su rivista]
Raparelli, Valeria; Pastori, Daniele; Pignataro, Serena Francesca; Vestri, Anna Rita; Pignatelli, Pasquale; Cangemi, Roberto; Proietti, Marco; Davì, Giovanni; Hiatt, William Robert; Lip, Gregory Yoke Hong; Corazza, Gino Roberto; Perticone, Francesco; Violi, Francesco; Basili, Stefania; Alessandri, C.; Serviddio, G.; Palange, P.; Greco, E.; Bruno, G.; Averna, M.; Giammanco, A.; Sposito, P.; De Cristofaro, R.; Carulli, L.; De Gennaro, L.; Pellegrini, E.; Cominacini, L.; Mozzini, C.; Pasini, A. F.; Sprovieri, M.; Spagnuolo, V.; Cerqua, G.; Cerasola, G.; Mulé, G.; Barbagallo, M.; Lo Sciuto, S.; Monteverde, A.; Saitta, A.; Lo Gullo, A.; Malatino, L.; Cilia, C.; Terranova, V.; Pisano, M.; Pinto, A.; Di Raimondo, D.; Tuttolomondo, A.; Conigliaro, R.; Signorelli, S.; De Palma, D.; Galderisi, M.; Cudemo, G.; Galletti, F.; Fazio, V.; De Luca, N.; Meccariello, A.; Caputo, D.; De Donato, M. T.; Iannuzi, A.; Bresciani, A.; Giunta, R.; Utili, R.; Iorio, V.; Adinolfi, L. E.; Sellitto, C.; Iuliano, N.; Bellis, P.; Tirelli, P.; Sacerdoti, D.; Vanni, D.; Iuliano, L.; Ciacciarelli, M.; Pacelli, A.; Palazzuoli, A.; Cacciafesta, M.; Gueli, N.; Lo Iacono, C.; Brusco, S.; Verrusio, W.; Nobili, L.; Tarquinio, N.; Pellegrini, F.; Vincentelli, G. M.; Ravallese, F.; Santini, C.; Letizia, C.; Petramala, L.; Zinnamosca, L.; Minisola, S.; Cilli, M.; Colangelo, L.; Falaschi, P.; Martocchia, A.; Pastore, F.; Bertazzoni, G.; Attalla El Halabieh, E.; Paradiso, M.; Lizzi, E. M.; Timmi, S.; Battisti, P.; Cerci, S.; Ciavolella, M.; Di Veroli, C.; Malci, F.; De Ciocchis, A.; Abate, D.; Castellino, P.; Zanoli, L.; Fidone, F.; Mannarino, E.; Pasqualini, L.; Oliverio, G.; Pende, A.; Artom, N.; Ricchio, R.; Fimognari, F. L.; Alletto, M.; Messina, S.; Sesti, G.; Arturi, F.; Succurro, E.; Fiorentino, T. V.; Pedace, E.; Scarpino, P. E.; Carullo, G.; Maio, R.; Sciacqua, A.; Frugiuele, P.; Spagnuolo, V.; Battaglia, G.; Atzori, S.; Delitala, G.; Angelucci, E.; Sestili, S.; Traisci, G.; De Feudis, L.; Di Michele, D.; Fava, A.; Balsano, C.; De Ciantis, P.; Desideri, G.; Camerota, A.; Mezzetti, M.; Gresele, P.; Vedovati, C.; Fierro, T.; Puccetti, L.; Bertolotti, M.; Mussi, C.; Boddi, M.; Savino, A.; Contri, S.; Degl’Innocenti, G.; Saller, A.; Fabris, F.; Pesavento, R.; Filippi, L.; Vedovetto, V.; Puato, M.; Fabris, F.; Treleani, M.; De Luca, E.; De Zaiacomo, F.; Giantin, V.; Semplicini, A.; Minuz, P.; Romano, S.; Fantin, F.; Manica, A.; Stockner, I.; Pattis, P.; Gutmann, B.; Catena, C.; Colussi, G.; Sechi, L. A.; Annoni, G.; Bruni, A. A.; Castagna, A.; Spinelli, D.; Miceli, E.; Padula, D.; Schinco, G.; Spreafico, S.; Secchi, B.; Vanoli, M.; Casella, G.; Pulixi, E. A.; Sansone, L.; Serra, M. G.; Longo, S.; Antonaci, S.; Belfiore, A.; Frualdo, M.; Palasciano, G.; Ricci, L.; Ventrella, F.; Bianco, C.; Santovito, D.; Cipollone, F.; Nicolai, S.; Salvati, F.; Rini, G. B.; Scozzari, F.; Muiesan, M. L.; Salvetti, M.; Bazza, A.; Picardi, A.; Vespasiani-Gentilucci, U.; De Vincentis, A.; Cosio, P.; Terzolo, M.; Madaffari, B.; Parasporo, B.; Fenoglio, L.; Bracco, C.; Melchio, R.; Gentili, T.; Salvi, A.; Nitti, C.; Gabrielli, A.; Martino, G. P.; Capucci, A.; Brambatti, M.; Sparagna, A.; Tirotta, D.; Andreozzi, P.; Ettorre, E.; Viscogliosi, G.; Servello, A.; Musumeci, M.; Delfino, M.; Giorgi, A.; Glorioso, N.; Melis, G.; Marras, G.; Matta, M.; Sacco, A.; Stellitano, E.; Scordo, A.; Russo, F.; Caruso, A. A.; Porreca, E.; Tana, M.; Ferri, C.; Cheli, P.; Portincasa, P.; Muscianisi, G.; Giordani, S.; Stanghellini, V.; Sabbà, C.; Mancuso, G.; Bartone, M.; Calipari, D.; Arcidiacono, G.; Bellanuova, I.; Ferraro, M.; Marigliano, G.; Cozzolino, D.; Lampitella, A.; Acri, V.; Galasso, D.; Mazzei, F.; Buratti, A.; Galasso, S.; Porta, M.; Brizzi, M. F.; Fattorini, A.; Sampietro, F.; D’Angelo, A.; Manfredini, R.; Pala, M.; Fabbian, F.; Moroni, C.; Valente, L.; Lopreiato, F.; Parente, F.
abstract
Chronic obstructive pulmonary disease (COPD) increases the risk of mortality in non-valvular atrial fibrillation (NVAF) patients. Data on the relationship of COPD to major cardiovascular events (MACE) in AF have not been defined. The aim of the study is to assess the predictive value of COPD on incident MACE in NVAF patients over a 3-year follow-up. In the Atrial Fibrillation Registry for Ankle-Brachial Index Prevalence Assessment-Collaborative Italian Study (ARAPACIS) cohort, we evaluate the impact of COPD on the following clinical endpoints: MACE (including vascular death, fatal/non-fatal MI and stroke/TIA), cardiovascular (CV) death and all-cause mortality. Among 2027 NVAF patients, patients with COPD (9%) are more commonly male, elderly and at higher thromboembolic risk. During a median 36.0 months follow-up, 186 patients experienced MACE: vascular death (n = 72), MI (n = 57), stroke/TIA (n = 57). All major outcomes (including stroke/TIA, MI, vascular death, and all-cause death) are centrally adjudicated. Kaplan–Meier curves show that NVAF patients with COPD are at higher risk for MACE (p < 0.001), CV death (p < 0.001) and all-cause death (p < 0.001). On Cox proportional hazard analysis, COPD is an independent predictor of MACE (Hazard ratio [HR] 1.77, 95% Confidence Intervals [CI] 1.20–2.61; p = 0.004), CV death (HR 2.73, 95% CI 1.76–4.23; p < 0.0001) and all-cause death (HR 2.16, 95% CI 1.48–3.16; p < 0.0001). COPD is an independent predictor of MACE, CV death and all-cause death during a long-term follow-up of NVAF patients.
2018
- Polypharmacy in older people: lessons from 10 years of experience with the REPOSI register
[Articolo su rivista]
Mannucci, Pier Mannuccio; Nobili, Alessandro; Pasina, Luca; Mannucci, Pier Mannuccio; Tettamanti, Mauro; Franchi, Carlotta; Corrao, Salvatore; Marengoni, Alessandra; Salerno, Francesco; Cesari, Matteo; Perticone, Francesco; Licata, Giuseppe; Violi, Francesco; Corazza, Gino Roberto; Franchi, Carlotta; Cortesi, Laura; Tettamanti, Mauro; Cortesi, Laura; Ardoino, Ilaria; Prisco, Domenico; Silvestri, Elena; Cenci, Caterina; Emmi, Giacomo; Biolo, Gianni; Zanetti, Michela; Guadagni, Martina; Zaccari, Michele; Vanoli, Massimo; Grignani, Giulia; Pulixi, Edoardo Alessandro; Bernardi, Mauro; Bassi, Silvia Li; Santi, Luca; Zaccherini, Giacomo; Mannarino, Elmo; Lupattelli, Graziana; Bianconi, Vanessa; Paciullo, Francesco; Nuti, Ranuccio; Valenti, Roberto; Ruvio, Martina; Cappelli, Silvia; Palazzuoli, Alberto; Olivieri, Oliviero; Girelli, Domenico; Matteazzi, Thomas; Barbagallo, Mario; Dominguez, Ligia; Cocita, Floriana; Beneduce, Vincenza; Plances, Lidia; Zoli, Marco; Lazzari, Ilaria; Brunori, Mattia; Pasini, Franco Laghi; Capecchi, Pier Leopoldo; Palasciano, Giuseppe; Modeo, Maria Ester; Di Gennaro, Carla; Cappellini, Maria Domenica; Maira, Diletta; Di Stefano, Valeria; Fabio, Giovanna; Seghezzi, Sonia; Mancarella, Marta; Cesari, Matteo; Rossi, Paolo Dionigi; Damanti, Sarah; Clerici, Marta; Conti, Federica; Corazza, Gino Roberto; Miceli, Emanuela; Lenti, Marco Vincenzo; Pisati, Martina; Dominioni, Costanza Caccia; Murialdo, Giovanni; Marra, Alessio; Cattaneo, Federico; Secchi, Maria Beatrice; Ghelfi, Davide; Anastasio, Luigi; Sofia, Lucia; Carbone, Maria; Cipollone, Francesco; Guagnano, Maria Teresa; Angelucci, Ermanno; Valeriani, Emanuele; Mancuso, Gerardo; Calipari, Daniela; Bartone, Mosè; Delitala, Giuseppe; Berria, Maria; Muscaritoli, Maurizio; Molfino, Alessio; Petrillo, Enrico; Zuccalà, Giuseppe; D’Aurizio, Gabriella; Romanelli, Giuseppe; Marengoni, Alessandra; Zucchelli, Alberto; Picardi, Antonio; Gentilucci, Umberto Vespasiani; Gallo, Paolo; Dell’Unto, Chiara; Annoni, Giorgio; Corsi, Maurizio; Bellelli, Giuseppe; Zazzetta, Sara; Mazzola, Paolo; Szabo, Hajnalka; Bonfanti, Alessandra; Arturi, Franco; Succurro, Elena; Rubino, Mariangela; Serra, Maria Grazia; Bleve, Maria Antonietta; Gasbarrone, Laura; Sajeva, Maria Rosaria; Brucato, Antonio; Ghidoni, Silvia; Fabris, Fabrizio; Bertozzi, Irene; Bogoni, Giulia; Rabuini, Maria Victoria; Cosi, Elisabetta; Manfredini, Roberto; Fabbian, Fabio; Boari, Benedetta; De Giorgi, Alfredo; Tiseo, Ruana; Paolisso, Giuseppe; Rizzo, Maria Rosaria; Borghi, Claudio; Strocchi, Enrico; De Sando, Valeria; Pareo, Ilenia; Sabbà, Carlo; Vella, Francesco Saverio; Suppressa, Patrizia; Agosti, Pasquale; Schilardi, Andrea; Loparco, Francesca; Fenoglio, Luigi; Bracco, Christian; Giraudo, Alessia Valentina; Fargion, Silvia; Periti, Giulia; Porzio, Marianna; Tiraboschi, Slivia; Peyvandi, Flora; Rossio, Raffaella; Ferrari, Barbara; Colombo, Giulia; Monzani, Valter; Savojardo, Valeria; Folli, Christian; Ceriani, Giuliana; Salerno, Francesco; Pallini, Giada; Dallegri, Franco; Ottonello, Luciano; Liberale, Luca; Caserza, Lara; Salam, Kassem; Liberato, Nicola Lucio; Tognin, Tiziana; Bianchi, Giovanni Battista; Giaquinto, Sabrina; Purrello, Francesco; Di Pino, Antonino; Piro, Salvatore; Rozzini, Renzo; Falanga, Lina; Spazzini, Elena; Ferrandina, Camillo; Montrucchio, Giuseppe; Petitti, Paolo; Salmi, Raffaella; Gaudenzi, Piergiorgio; Violi, Francesco; Perri, Ludovica; Landolfi, Raffaele; Montalto, Massimo; Mirijello, Antonio; Guasti, Luigina; Castiglioni, Luana; Maresca, Andrea; Squizzato, Alessandro; Molaro, Marta; Grossi, Alessandra; Bertolotti, Marco; Mussi, Chiara; Libbra, Maria Vittoria; Dondi, Giulia; Pellegrini, Elisa; Carulli, Lucia; Perticone, Francesco; Colangelo, Lidia; Falbo, Tania; Stanghellini, Vincenzo; De Giorgio, Roberto; Ruggeri, Eugenio; del Vecchio, Sara; Salvi, Andrea; Leonardi, Roberto; Damiani, Giampaolo; Gabrielli, Armando; Capeci, William; Mattioli,
abstract
As a consequence of population aging, we have witnessed in internal medicine hospital wards a progressive shift from a population of in-patients relatively young and mainly affected by a single ailment to one of ever older and more and more complex patients with multiple chronic diseases, followed as out-patients by many different specialists with poor integration and inevitably treated with multiple medications. Polypharmacy (defined as the chronic intake of five or more drugs) is associated with increased risks of drug–drug interactions and related adverse effects, prescription and intake errors, poor compliance, re-hospitalization and mortality. With this background, the Italian Society of Internal Medicine chose to start in 2008 a prospective register called REPOSI (REgistro POliterapie SIMI, Società Italiana di Medicina Interna) in internal medicine and geriatric hospital wards. The country wide register is an ongoing observatory on multimorbidity and polypharmacy in the oldest old, with the goal to improve prescription appropriateness and, thus to avoid potentially inappropriate medications. The main findings of the register, that has accrued so far, 7005 older patients throughout a 10 year period, are summarized herewith, with special emphasis on the main patterns of poor prescription appropriateness and related risks of adverse events.
2018
- Senior citizens
[Articolo su rivista]
Desideri, G.; Bertolotti, M.
abstract
2018
- Use of oral anticoagulant drugs in older patients with atrial fibrillation in internal medicine wards
[Articolo su rivista]
Proietti, Marco; Antoniazzi, Stefania; Monzani, Valter; Santalucia, Paola; Franchi, Carlotta; Fenoglio, Luigi M.; Melchio, Remo; Fabris, Fabrizio; Sartori, Maria Teresa; Manfredini, Roberto; De Giorgi, Alfredo; Fabbian, Fabio; Biolo, Gianni; Zanetti, Michela; Altamura, Nicola; Sabbà, Carlo; Suppressa, Patrizia; Bandiera, Francesco; Usai, Carlo; Murialdo, Giovanni; Fezza, Francesca; Marra, Alessio; Castelli, Francesca; Cattaneo, Federico; Beccati, Valentina; di Minno, Giovanni; Tufano, Antonella; Contaldi, Paola; Lupattelli, Graziana; Bianconi, Vanessa; Cappellini, Domenica; Hu, Cinzia; Minonzio, Francesca; Fargion, Silvia; Burdick, Larry; Francione, Paolo; Peyvandi, Flora; Rossio, Raffaella; Colombo, Giulia; Monzani, Valter; Ceriani, Giuliana; Lucchi, Tiziano; Brignolo, Barbara; Manfellotto, Dario; Caridi, Irene; Corazza, Gino Roberto; Miceli, Emanuela; Padula, Donatella; Fraternale, Giacomo; Guasti, Luigina; Squizzato, Alessandro; Maresca, Andrea; Liberato, Nicola Lucio; Tognin, Tiziana; Rozzini, Renzo; Bellucci, Francesco Baffa; Muscaritoli, Maurizio; Molfino, Alessio; Petrillo, Enrico; Dore, Maurizio; Mete, Francesca; Gino, Miriam; Franceschi, Francesco; Gabrielli, Maurizio; Perticone, Francesco; Perticone, Maria; Bertolotti, Marco; Mussi, Chiara; Borghi, Claudio; Strocchi, Enrico; Durazzo, Marilena; Fornengo, Paolo; Dallegri, Franco; Ottonello, Luciano Carlo; Salam, Kassem; Caserza, Lara; Barbagallo, Mario; Di Bella, Giovanna; Annoni, Giorgio; Bruni, Adriana Antonella; Odetti, Patrizio; Nencioni, Alessio; Monacelli, Fiammetta; Napolitano, Armando; Brucato, Antonio; Valenti, Anna Chiara; Castellino, Pietro; Zanoli, Luca; Mazzeo, Marco
abstract
Atrial fibrillation is independently associated with a higher risk of morbidity and mortality, in particular with an increased risk of thromboembolic events. Use of oral anticoagulant (OAC) drugs reduces the risk of stroke and systemic embolism, as well as mortality among patients with AF. With the aim to provide evidences about use of OAC and NOACs in older hospitalized patients, we here report data about the retrospective observational phase of the “ Simulation-Based Technologies to Improve the Appropriate Use of Oral Anticoagulants in Hospitalized Elderly Patients with Atrial Fibrillation” (SIM-AF) Trial
2018
- [Consensus document and recommendations for the prevention of cardiovascular disease in Italy - 2018]
[Articolo su rivista]
Volpe, Massimo; Tocci, Giuliano; Accettura, Domenico; Battistoni, Allegra; Bellone, Simonetta; Bellotti, Paolo; Bertolotti, Marco; Borghi, Claudio; Casasco, Maurizio; Consoli, Agostino; Coppini, Raffaele; Corsini, Alberto; Costanzo, Gianfranco; Desideri, Giovambattista; Ferri, Claudio; Galanti, Giorgio; Giada, Franco; Icardi, Giancarlo; Lombardi, Niccolò; Modena, Maria Grazia; Modesti, Pietro Amedeo; Monti, Giorgio; Mugelli, Alessandro; Orsi, Andrea; Parati, Gianfranco; Pedretti, Roberto F. E.; Perseghin, Gianluca; Pirro, Matteo; Ricotti, Roberta; Rizzoni, Damiano; Rotella, Carlo; Rubattu, Speranza; Salvetti, Guido; Sarto, Patrizio; Tassinari, Federico; Trimarco, Bruno; de Kreutzenberg, Saula Vigili; Volpe, Roberto
abstract
Cardiovascular prevention represents a cornerstone of modern strategies to reduce the burden of cardiovascular disease. It is of key importance to prevent cardiovascular diseases and associated events, not only to reduce morbidity and mortality, but also to increase the years of wellness in the aging population and to make the growing socio-economic burden imposed by cardiovascular events more sustainable.The current approach to prevention is based on an integrated use of effective lifestyle measures and, whenever appropriate, of antihypertensive and antidiabetic drugs, lipid-lowering agents and antiplatelet drugs.Given that population characteristics, in terms of ethnicity, demography and lifestyle habits, and healthcare system organizations differ among countries, international guidelines are not always applicable to specific countries and, often, are difficult to translate into daily clinical practice.In order to afford the specific features of Italy, 10 Scientific Societies and Research Institutions, mostly involved in preventive strategies, contributed to the present Italian consensus document, which includes brief, practical recommendations to support the preventive actions within the physician community and the general practice setting.
2017
- Carotid plaque detection improves the predictve value of CHA2DS2-VASc score in patients with non-valvular atrial fibrilation: The ARAPACIS Study
[Articolo su rivista]
Basili, S.; Loffredo, L.; Pastori, D.; Proieti, M.; Farcomeni, A.; Vesti, A. R.; Pignatelli, P.; Davi, G.; Hiatt, W. R.; Lip, G. Y. H.; Corazza, G. R.; Perticone, F.; Violi, F.; Alessandri, C.; Serviddio, G.; Fascetti, S.; Palange, P.; Greco, E.; Bruno, G.; Averna, M.; Giammanco, A.; Sposito, P.; De Cristofaro, R.; De Gennaro, L.; Carulli, L.; Pellegrini, E.; Cominacini, L.; Mozzini, C.; Pasini, A. F.; Sprovieri, M.; Spagnuolo, V.; Cerqua, G.; Cerasola, G.; Mule, G.; Barbagallo, M.; Lo Sciuto, S.; Monteverde, A.; Saitta, A.; Lo Gullo, A.; Malatino, L.; Ciia, C.; Terranova, V.; Pisano, M.; Pinto, A.; Di Raimondo, D.; Tuttolomondo, A.; Conigliaro, R.; Signorelli, S.; De Palma, D.; Galderisi, M.; Cudemo, G.; Galletti, F.; Fazio, V.; De Luca, N.; Meccariello, A.; Caputo, D.; De Donato, M. T.; Iannuzi, A.; Bresciani, A.; Giunta, R.; Utili, R.; Iorio, V.; Adinolfi, L. E.; Sellitto, C.; Iuliano, N.; Bellis, P.; Tirelli, P.; Sacerdoti, D.; Vanni, D.; Iuliano, L.; Ciacciarelli, M.; Pacelli, A.; Palazzuoli, A.; Cacciafesta, M.; Gueli, N.; Lo Iacono, G.; Brusco, S.; Verrusio, W.; Nobili, L.; Tarquinio, N.; Pellegrini, F.; Vincentelli, G. M.; Ravallese, F.; Santini, C.; Letizia, C.; Petramala, L.; Zinnamosca, L.; Minisola, S.; Cilli, M.; Savoriti, C.; Colangelo, L.; Falaschi, P.; Martocchia, A.; Pastore, F.; Bertazzoni, G.; Attalla El Halabieh, E.; Paradiso, M.; Lizzi, E. M.; Timmi, S.; Battisti, P.; Cerci, S.; Ciavolella, M.; Di Veroli, C.; Malei, F.; De Ciocchis, A.; Abate, D.; Castellino, P.; Zanoli, L.; Fidone, F.; Mannarino, E. T.; Pasqualini, L.; Oliverio, G.; Pende, A.; Aitom, N.; Ricchio, R.; Fimognari, F. L.; Alletto, M.; Messina, S.; Sesti, G.; Arturi, F.; Fiorentino, T. V.; Pedace, E.; Scarpino, P. E.; Carullo, G.; Maio, R.; Sciacqua, A.; Frugiuele, P.; Spagnuolo, V.; Battaglia, G.; Atzori, S.; Delitala, G.; Angelucci, E.; Sestili, S.; Traisci, G.; De Feudis, L.; Di Michele, D.; Fava, A.; Balsano, C.; De Ciantis, P.; Desideri, G.; Camerota, A.; Mezzetti, M.; Gresele, P.; Vedovati, C.; Fierro, T.; Puccetti, L.; Bertolotti, M.; Mussi, C.; Boddi, M.; Savino, A.; Contri, S.; Degl'Innocenti, G.; Sailer, A.; Fabris, F.; Pesavento, R.; Filippi, L.; Vedovetto, V.; Puato, M.; Fabris, F.; Treleani, M.; De Luca, E.; De Zaiacomo, F.; Giantin, V.; Semplicini, A.; Minuz, P.; Romano, S.; Fantin, F.; Manica, A.; Stockner, I.; Pattis, P.; Gutmann, B.; Catena, C.; Colussi, G.; Sechi, L. A.; Annoni, G.; Bruni, A. A.; Castagna, A.; Spinelli, D.; Miceli, E.; Paduia, D.; Schinco, G.; Spreafico, S.; Secchi, B.; Vanoli, M.; Casella, G.; Pulixi, E. A.; Sansone, L.; Serra, M. G.; Longo, S.; Antonaci, S.; Belfiaore, A.; Frualdo, M.; Palasciano, G.; Ricci, L.; Ventrella, F.; Bianco, C.; Santovito, D.; Cipollone, F.; Nicolai, S.; Salvati, F.; Rini, G. B.; Scozzari, F.; Muiesan, M. L.; Salvetti, M.; Bazza, A.; Picardi, A.; Vespasiani-Gentilucci, U.; De Vincentis, A.; Cosio, P.; Terzolo, M.; Madaffari, B.; Parasporo, B.; Fenoglio, L.; Bracco, C.; Melchio, R.; Gentili, T.; Salvi, A.; Nitti, C.; Gabrielli, A.; Martino, G. P.; Capucci, A.; Brambatti, M.; Sparagna, A.; Tirotta, D.; Andreozzi, P.; Ettorre, E.; Viscogliosi, G.; Servello, A.; Musumeci, M.; Rossi Fanelli, F.; Delfino, M.; Giorgi, A.; Glorioso, N.; Melis, G.; Marras, G.; Matta, M.; Sacco, A.; Stellitano, E.; Scordo, A.; Russo, F.; Caruso, A. A.; Porreca, E.; Tana, M.; Ferri, C.; Cheli, P.; Portincasa, P.; Muscianisi, G.; Giordani, S.; Stanghellini, V.; Sabba, C.; Mancuso, G.; Bartone, M.; Calipari, D.; Arcidiacono, G.; Bellanuova, I.; Ferraro, M.; Marigliano, G.; Cozzolino, D.; Lampitella, A.; Acri, V.; Galasso, D.; Mazzei, F.; Galasso, S.; Buratti, A.; Porta, M.; Brizzi, M. F.; Fattorini, A.; Sampietro, F.; D'Angelo, A.; Manfredini, R.; Pala, M.; Fabbian, F.; Moroni, C.; Valente, L.; Lopreiato, F.; Parente, F.; Granata, M.; Moia, M.; Braham, S.; Rossi, M.; Pesce, M.; Gentile, A.; Catozzo, V.; Baciarello, G.; Cosimati, A.; Ageno, W.; Rancan, E.; Guasti, L.; Ciccaglioni, A.; Negri, S.; Polselli, M.; P
abstract
Background and aims: Vascular disease (VD), as assessed by history of myocardial infarction or peripheral artery disease or aortic plaque, increases stroke risk in atrial fibrillation (AF), and is a component of risk assessment using the CHA2DS2-VASc score. We investigated if systemic atherosclerosis as detected by ultrasound carotid plaque (CP) could improve the predictive value of the CHA2DS2-VASC score. Methods: We analysed data from the ARAPACIS study, an observational study including 2027 Ialian patents with non-valvular AF, in whom CP was detected using Doppler Ultrasonography. Results: VD was reported in 351 (17.3%) patients while CP was detected in 16.6% patents. Adding CP to the VD definition leaded to higher VD prevalence (30.9%). During a median [IQR] follow-up time of 36 months, 56 (2.8%) stroke/TIA events were recorded. Survival analysis showed that conventional VD alone did not increase the risk of stroke (Log-Rank: 0.009, p = 0.924), while addition of CP to conventional VD was significantly associated to an increased risk of stroke (LR: 5.730, p = 0.017). Cox regression analysis showed that VD + CP was independently associated with stroke (HR: 1.78, 95% CI: 1.05-3.01, p = 0.0318). Reclassification analysis showed that VD + CP allowed a significant risk reclassification when compared to VD alone in predicting stroke at 36 months (NRI: 0.192, 95% CI: 0.028-0.323, p = 0.032). Conclusions: In non-valvular AF patients the addition of ultrasound detection of carotid plaque to conventional VD significantly increases the pedictive value of CHA2DS2-VASc score for stroke.
2017
- Case of an old man with aortic dissection type A and enlarging meningioma
[Articolo su rivista]
Lancellotti, Giulia; Rontauroli, Caterina; Turrini, Elisabete; Bertolotti, Marco; Mussi, Chiara
abstract
In this paper we describe a clinical case of an old man with a large meningioma and a concomitant diagnosis of atypa A aortic dissection.
2017
- Defining aging phenotypes and related outcomes: Clues to recognize frailty in hospitalized older patients
[Articolo su rivista]
Marcucci, M.; Franchi, C.; Nobili, A.; Mannucci, P. M.; Ardoino, I.; Tettamanti, M.; Pasina, L.; Perticone, F.; Salerno, F.; Corrao, S.; Marengoni, A.; Licata, G.; Violi, F.; Corazza, G. R.; Eldin, T. K.; Di Blanca, M. P. D.; Djade, C. D.; Cortesi, L.; Prisco, D.; Silvestri, E.; Cenci, C.; Emmi, G.; Biolo, G.; Guarnieri, G.; Zanetti, M.; Fernandes, G.; Vanoli, M.; Grignani, G.; Casella, G.; Bernardi, M.; Bassi, S. L.; Santi, L.; Zaccherini, G.; Mannarino, E.; Lupattelli, G.; Bianconi, V.; Paciullo, F.; Nuti, R.; Valenti, R.; Ruvio, M.; Cappelli, S.; Palazzuoli, A.; Salvatore, T.; Sasso, F. C.; Girelli, D.; Olivieri, O.; Matteazzi, T.; Barbagallo, M.; Plances, L.; Alcamo, R.; Calvo, L.; Valenti, M.; Zoli, M.; Arno, R.; Pasini, F. L.; Capecchi, P. L.; Bicchi, M.; Palasciano, G.; Modeo, M. E.; Peragine, M.; Pappagallo, F.; Pugliese, S.; Di Gennaro, C.; Postiglione, A.; Barbella, M. R.; De Stefano, F.; Cappellini, M. D.; Fabio, G.; Seghezzi, S.; De Amicis, M. M.; Mari, D.; Rossi, P. D.; Damanti, S.; Ottolini, B. B.; Miceli, E.; Lenti, M. V.; Padula, D.; Murialdo, G.; Marra, A.; Cattaneo, F.; Secchi, M. B.; Ghelfi, D.; Anastasio, L.; Sofia, L.; Carbone, M.; Davi, G.; Guagnano, M. T.; Sestili, S.; Mancuso, G.; Calipari, D.; Bartone, M.; Meroni, M. R.; Perin, P. C.; Lorenzati, B.; Gruden, G.; Bruno, G.; Amione, C.; Fornengo, P.; Tassara, R.; Melis, D.; Rebella, L.; Delitala, G.; Pretti, V.; Masala, M. S.; Bolondi, L.; Rasciti, L.; Serio, I.; Fanelli, F. R.; Amoroso, A.; Molfino, A.; Petrillo, E.; Zuccala, G.; Franceschi, F.; De Marco, G.; Chiara, C.; Marta, S.; Romanelli, G.; Amolini, C.; Chiesa, D.; Picardi, A.; Gentilucci, U. V.; Gallo, P.; Annoni, G.; Corsi, M.; Zazzetta, S.; Bellelli, G.; Arturi, F.; Succurro, E.; Rubino, M.; Sesti, G.; Loria, P.; Becchi, M. A.; Martucci, G.; Fantuzzi, A.; Maurantonio, M.; Carta, S.; Atzori, S.; Serra, M. G.; Bleve, M. A.; Gasbarrone, L.; Sajeva, M. R.; Brucato, A.; Ghidoni, S.; Di Corato, P.; Agnelli, G.; Marchesini, E.; Fabris, F.; Carlon, M.; Turatto, F.; Baritusso, A.; Manfredini, R.; Molino, C.; Pala, M.; Fabbian, F.; Boari, B.; De Giorgi, A.; Paolisso, G.; Rizzo, M. R.; Laieta, M. T.; Rini, G.; Mansueto, P.; Pepe, I.; Borghi, C.; Strocchi, E.; De Sando, V.; Sabba, C.; Vella, F. S.; Suppressa, P.; Valerio, R.; Capobianco, C.; Fenoglio, L.; Bracco, C.; Giraudo, A. V.; Testa, E.; Serraino, C.; Fargion, S.; Bonara, P.; Periti, G.; Porzio, M.; Peyvandi, F.; Tedeschi, A.; Rossio, R.; Monzani, V.; Savojardo, V.; Folli, C.; Magnini, M.; Conca, A.; Gobbo, G.; Balduini, C. L.; Bertolino, G.; Provini, S.; Quaglia, F.; Dallegri, F.; Ottonello, L.; Liberale, L.; Chin, W. S.; Carassale, L.; Caporotundo, S.; Traisci, G.; De Feudis, L.; Di Carlo, S.; Liberato, N. L.; Buratti, A.; Tognin, T.; Bianchi, G. B.; Giaquinto, S.; Purrello, F.; Di Pino, A.; Piro, S.; Rozzini, R.; Falanga, L.; Montrucchio, G.; Greco, E.; Tizzani, P.; Petitti, P.; Perciccante, A.; Coralli, A.; Salmi, R.; Gaudenzi, P.; Gamberini, S.; Semplicini, A.; Gottardo, L.; Vendemiale, G.; Serviddio, G.; Forlano, R.; Masala, C.; Mammarella, A.; Raparelli, V.; Basili, S.; Perri, L.; Landolfi, R.; Montalto, M.; Mirijello, A.; Vallone, C.; Bellusci, M.; Setti, D.; Pedrazzoli, F.; Guasti, L.; Castiglioni, L.; Maresca, A.; Squizzato, A.; Molaro, M.; Bertolotti, M.; Mussi, C.; Libbra, M. V.; Miceli, A.; Pellegrini, E.; Carulli, L.; Sciacqua, A.; Quero, M.; Bagnato, C.; Corinaldesi, R.; De Giorgio, R.; Serra, M.; Grasso, V.; Ruggeri, E.; Salvi, A.; Leonardi, R.; Grassini, C.; Mascherona, I.; Minelli, G.; Maltese, F.; Gabrielli, A.; Mattioli, M.; Capeci, W.; Martino, G. P.; Messina, S.; Ghio, R.; Favorini, S.; Dal Col, A.; Minisola, S.; Colangelo, L.; Afeltra, A.; Alemanno, P.; Marigliano, B.; Castellino, P.; Blanco, J.; Zanoli, L.; Cattaneo, M.; Fracasso, P.; Amoruso, M. V.; Saracco, V.; Fogliati, M.; Bussolino, C.; Durante, V.; Eusebi, G.; Tirotta, D.; Mete, F.; Gino, M.; Cittadini, A.; Arcopinto, M.; Salzano, A.; Bobbio, E.; Marra, A. M.; Sirico, D.;
abstract
Background: Because frailty is a complex phenomenon associated with poor outcomes, the identification of patient profiles with different care needs might be of greater practical help than to look for a unifying definition. This study aimed at identifying aging phenotypes and their related outcomes in order to recognize frailty in hospitalized older patients. Methods: Patients aged 65 or older enrolled in internal medicine and geriatric wards participating in the REPOSI registry. Relationships among variables associated to sociodemographic, physical, cognitive, functional, and medical status were explored using a multiple correspondence analysis. The hierarchical cluster analysis was then performed to identify possible patient profiles. Multivariable logistic regression was used to verify the association between clusters and outcomes (in-hospital mortality and 3-month postdischarge mortality and rehospitalization). Results: 2,841 patients were included in the statistical analyses. Four clusters were identified: the healthiest (I); those with multimorbidity (II); the functionally independent women with osteoporosis and arthritis (III); and the functionally dependent oldest old patients with cognitive impairment (IV). There was a significantly higher in-hospital mortality in Cluster II (odds ratio [OR] = 2.27, 95% confidence interval [CI] = 1.15-4.46) and Cluster IV (OR = 5.15, 95% CI = 2.58-10.26) and a higher 3-month mortality in Cluster II (OR = 1.66, 95% CI = 1.13-2.44) and Cluster IV (OR = 1.86, 95% CI = 1.15-3.00) than in Cluster I. Conclusions: Using alternative analytical techniques among hospitalized older patients, we could distinguish different frailty phenotypes, differently associated with adverse events. The identification of different patient profiles can help defining the best care strategy according to specific patient needs.
2017
- Effects of cholecalciferol supplementation in patients with stable heart failure and low vitamin D levels (ECSPLOIT-D). A double-blind, randomized, placebo-controlled pilot study
[Articolo su rivista]
Turrini, Fabrizio; Scarlini, Stefania; Giovanardi, Paolo; Messora, Roberto; Roli, Laura; Chester, Johanna Mary; Mussi, Chiara; Bertolotti, Marco; Trenti, Tommaso; Bondi, Marco
abstract
The aim of this study was to investigate the effects of vitamin D (VD) on the interaction among functional, echocardiographic and hormonal parameters in patients with heart failure (HF) and VD deficiency.
2017
- Multiclass HCV resistance to direct-acting antiviral failure in real-life patients advocates for tailored second-line therapies
[Articolo su rivista]
Di Maio, Velia C.; Cento, Valeria; Lenci, Ilaria; Aragri, Marianna; Rossi, Piera; Barbaliscia, Silvia; Melis, Michela; Verucchi, Gabriella; Magni, Carlo F.; Teti, Elisabetta; Bertoli, Ada; Antonucci, Francescopaolo; Bellocchi, Maria C.; Micheli, Valeria; Masetti, Chiara; Landonio, Simona; Francioso, Simona; Santopaolo, Francesco; Pellicelli, Adriano M.; Calvaruso, Vincenza; Gianserra, Laura; Siciliano, Massimo; Romagnoli, Dante; Cozzolongo, Raffaele; Grieco, Antonio; Vecchiet, Jacopo; Morisco, Filomena; Merli, Manuela; Brancaccio, Giuseppina; Di Biagio, Antonio; Loggi, Elisabetta; Mastroianni, Claudio M.; Pace Palitti, Valeria; Tarquini, Pierluigi; Puoti, Massimo; Taliani, Gloria; Sarmati, Loredana; Picciotto, Antonino; Vullo, Vincenzo; Caporaso, Nicola; Paoloni, Maurizio; Pasquazzi, Caterina; Rizzardini, Giuliano; Parruti, Giustino; Craxì, Antonio; Babudieri, Sergio; Andreoni, Massimo; Angelico, Mario; Perno, Carlo F.; Ceccherini-Silberstein, Francesca; MARIANI COSTANTINI, Renato; Iapadre, N.; Grimaldi, A.; Cozzolongo, R.; Andreone, P.; Verucchi, G.; Menzaghi, B.; Quirino, T.; Pisani, Vincenzo; Torti, C.; Vecchiet, J.; Bruzzone, B.; De Maria, A.; Marenco, S.; Nicolini, L. A.; Viscoli, C.; Casinelli, K.; Delle Monache, M.; Lichtner, M.; Aghemo, A.; Boccaccio, V.; Bruno, S.; Cerrone, M.; Colombo, M.; D'Arminio Monforte, A.; Danieli, E.; Donato, Francesco; Gubertini, G.; Lleo, A.; Magni, C. F.; Mancon, A.; Monico, S.; Niero, F.; Russo, M. L.; Gnocchi, M.; Orro, A.; Milanesi, L.; Baldelli, E.; Bertolotti, M.; Borghi, V.; Mussini, C.; Brancaccio, Giulia; Gaeta, G. B.; Lembo, V.; Sangiovanni, V.; Di Marco, V.; Mazzola, A.; Petta, S.; D'Amico, maria ester; Cacciatore, P.; Consorte, A.; Pieri, A.; Polilli, E.; Sozio, F.; Antenucci, Francesca; Aragri, M.; Baiocchi, L.; Barbaliscia, S.; Biliotti, E.; Biolato, M.; Carioti, L.; Ceccherini-Silberstein, F.; Cerasari, G.; Cerva, C.; Ciotti, M.; D'Ambrosio, C.; D'Ettorre, G.; De Leonardis, F.; De Sanctis, A.; Di Maio, V. C.; Di Paolo, D.; Furlan, C.; Gallo, P.; Gasbarrini, A.; Giannelli, V.; Grieco, S.; Lambiase, L.; Lattanzi, B.; Lenci, I.; Lula, R.; Malagnino, V.; Manuelli, M.; Miglioresi, L.; Milana, M.; Moretti, A.; Nosotti, L.; Palazzo, D.; Pellicelli, A.; Romano, M.; Sarrecchia, C.; Sforza, Diego; Sorbo, M. C.; Spaziante, M.; Svicher, V.; Tisone, G.; Vespasiani-Gentilucci, U.; D'Adamo, G.; Mangia, A.; Maida, I.; Mura, M. S.; Falconi, L.; Di Giammartino, D.
abstract
Background & Aims: Despite the excellent efficacy of direct-acting antivirals (DAA) reported in clinical trials, virological failures can occur, often associated with the development of resistance-associated substitutions (RASs). This study aimed to characterize the presence of clinically relevant RASs to all classes in real-life DAA failures. Methods: Of the 200 virological failures that were analyzed in 197 DAA-treated patients, 89 with pegylated-interferon+ribavirin (PegIFN+RBV) and 111 without (HCV-1a/1b/1g/2/3/4=58/83/1/6/24/25; 56.8% treatment experienced; 65.5% cirrhotic) were observed. Sanger sequencing of NS3/NS5A/NS5B was performed by home-made protocols, at failure (N=200) and whenever possible at baseline (N=70). Results: The majority of the virological failures were relapsers (57.0%), 22.5% breakthroughs, 20.5% non-responders. RAS prevalence varied according to IFN/RBV use, DAA class, failure type and HCV genotype/subtype. It was 73.0% in IFN group vs 49.5% in IFN free, with the highest prevalence of NS5A-RASs (96.1%), compared to NS3-RASs (75.9% with IFN, 70.5% without) and NS5B-RASs (66.6% with IFN, 20.4% without, in sofosbuvir failures). In the IFN-free group, RASs were higher in breakthrough/non-responders than in relapsers (90.5% vs 40.0%, P<.001). Interestingly, 57.1% of DAA IFN-free non-responders had a misclassified genotype, and 3/4 sofosbuvir breakthroughs showed the major-RAS-S282T, while RAS-L159F was frequently found in sofosbuvir relapsers (18.2%). Notably, 9.0% of patients showed also extra target RASs, and 47.4% of patients treated with â¥2 DAA classes showed multiclass resistance, including 11/11 NS3+NS5A failures. Furthermore, 20.0% of patients had baseline-RASs, which were always confirmed at failure. Conclusions: In our failure setting, RAS prevalence was remarkably high in all genes, with a partial exception for NS5B, whose limited resistance is still higher than previously reported. This multiclass resistance advocates for HCV resistance testing at failure, in all three genes for the best second-line therapeutic tailoring.
2017
- Pattern of in-hospital changes in drug use in the older people from 2010 to 2016
[Articolo su rivista]
Franchi, C.; Ardoino, I.; Nobili, A.; Pasina, L.; Mannucci, P. M.; Marengoni, A.; Perticone, F.; Tettamanti, M.; Salerno, F.; Corrao, S.; Licata, G.; Violi, F.; Corazza, G. R.; Marcucci, M.; Eldin, T. K.; Donatella Di Blanca, M. P.; Lanzo, G.; Astuto, S.; Cortesi, L.; Prisco, D.; Silvestri, E.; Cenci, C.; Emmi, G.; Biolo, G.; Guarnieri, G.; Zanetti, M.; Fernandes, G.; Chiuch, M.; Vanoli, M.; Grignani, G.; Casella, G.; Pulixi, E. A.; Bernardi, M.; Li Bassi, S.; Santi, L.; Zaccherini, G.; Mannarino, E.; Lupattelli, G.; Bianconi, V.; Paciullo, F.; Nuti, R.; Valenti, R.; Ruvio, M.; Cappelli, S.; Palazzuoli, A.; Salvatore, T.; Sasso, F. C.; Girelli, D.; Olivieri, O.; Matteazzi, T.; Barbagallo, M.; Plances, L.; Alcamo, R.; Calvo, L.; Valenti, M.; Zoli, M.; Arno, R.; Pasini, F. L.; Capecchi, P. L.; Bicchi, M.; Palasciano, G.; Modeo, M. E.; Peragine, M.; Pappagallo, F.; Pugliese, S.; Di Gennaro, C.; Postiglione, A.; Barbella, M. R.; De Stefano, F.; Cappellini, M. D.; Fabio, G.; Seghezzi, S.; De Amicis, M. M.; Mancarella, M.; Mari, D.; Rossi, P. D.; Damanti, S.; Ottolini, B. B.; Bonini, G.; Miceli, E.; Lenti, M. V.; Padula, D.; Murialdo, G.; Marra, A.; Cattaneo, F.; Secchi, M. B.; Ghelfi, D.; Anastasio, L.; Sofia, L.; Carbone, M.; Davi, G.; Guagnano, M. T.; Sestili, S.; Mancuso, G.; Calipari, D.; Bartone, M.; Meroni, M. R.; Perin, P. C.; Lorenzati, B.; Gruden, G.; Bruno, G.; Amione, C.; Fornengo, P.; Tassara, R.; Melis, D.; Rebella, L.; Delitala, G.; Pretti, V.; Masala, M. S.; Pes, C.; Bolondi, L.; Rasciti, L.; Serio, I.; Fanelli, F. R.; Amoroso, A.; Molfino, A.; Petrillo, E.; Zuccala, G.; Franceschi, F.; De Marco, G.; Chiara, C.; Marta, S.; D'Aurizio, G.; Romanelli, G.; Amolini, C.; Chiesa, D.; Picardi, A.; Gentilucci, U. V.; Gallo, P.; Annoni, G.; Corsi, M.; Zazzetta, S.; Bellelli, G.; Szabo, H.; Arturi, F.; Succurro, E.; Rubino, M.; Sesti, G.; Loria, P.; Becchi, M. A.; Martucci, G.; Fantuzzi, A.; Maurantonio, M.; Serra, M. G.; Bleve, M. A.; Gasbarrone, L.; Sajeva, M. R.; Brucato, A.; Ghidoni, S.; Di Corato, P.; Agnelli, G.; Marchesini, E.; Fabris, F.; Carlon, M.; Turatto, F.; Baritusso, A.; Amabile, A.; Omenetto, E.; Scarinzi, P.; Manfredini, R.; Molino, C.; Pala, M.; Fabbian, F.; Boari, B.; De Giorgi, A.; Paolisso, G.; Rizzo, M. R.; Laieta, M. T.; Rini, G.; Mansueto, P.; Pepe, I.; Borghi, C.; Strocchi, E.; De Sando, V.; Pareo, I.; Sabba, C.; Vella, F. S.; Suppressa, P.; Valerio, R.; Agosti, P.; Fontana, F.; Loparco, F.; Capobianco, C.; Fenoglio, L.; Bracco, C.; Giraudo, A. V.; Testa, E.; Serraino, C.; Fargion, S.; Bonara, P.; Periti, G.; Porzio, M.; Tiraboschi, S.; Peyvandi, F.; Tedeschi, A.; Rossio, R.; Monzani, V.; Savojardo, V.; Folli, C.; Magnini, M.; Conca, A.; Gobbo, G.; Pallini, G.; Valenti, M.; Balduini, C. L.; Bertolino, G.; Provini, S.; Quaglia, F.; Dallegri, F.; Ottonello, L.; Liberale, L.; Chin, W. S.; Carassale, L.; Caporotundo, S.; Traisci, G.; De Feudis, L.; Di Carlo, S.; Liberato, N. L.; Buratti, A.; Tognin, T.; Bianchi, G. B.; Giaquinto, S.; Purrello, F.; Di Pino, A.; Piro, S.; Rozzini, R.; Falanga, L.; Spazzini, E.; Montrucchio, G.; Greco, E.; Tizzani, P.; Petitti, P.; Perciccante, A.; Coralli, A.; Salmi, R.; Gaudenzi, P.; Gamberini, S.; Semplicini, A.; Gottardo, L.; Vendemiale, G.; Serviddio, G.; Forlano, R.; Masala, C.; Mammarella, A.; Raparelli, V.; Basili, S.; Perri, L.; Landolfi, R.; Montalto, M.; Mirijello, A.; Vallone, C.; Bellusci, M.; Setti, D.; Pedrazzoli, F.; Guasti, L.; Castiglioni, L.; Maresca, A.; Squizzato, A.; Molaro, M.; Bertolotti, M.; Mussi, C.; Libbra, M. V.; Miceli, A.; Pellegrini, E.; Carulli, L.; Veltri, F.; Sciacqua, A.; Quero, M.; Bagnato, C.; Colangelo, L.; Falbo, T.; De Giorgio, R.; Serra, M.; Grasso, V.; Ruggeri, E.; Ilaria, B.; Salvi, A.; Leonardi, R.; Grassini, C.; Mascherona, I.; Minelli, G.; Maltese, F.; Damiani, G.; Capeci, W.; Mattioli, M.; Martino, G. P.; Biondi, L.; Ormas, M.; Pettinari, P.; Romiti, R.; Messina, S.; Cavallaro, F.; Ghio, R.; Favorini, S.; Dal Col, A.; Minisola, S
abstract
Purpose: To assess the pattern of in-hospital changes in drug use in older patients from 2010 to 2016. Methods: People aged 65 years or more acutely hospitalized in those internal medicine and geriatric wards that did continuously participate to the REgistro POliterapie Società Italiana di Medicina Interna register from 2010 to 2016 were selected. Drugs use were categorized as 0 to 1 drug (very low drug use), 2 to 4 drugs (low drug use), 5 to 9 drugs (polypharmacy), and 10 or more drugs (excessive polypharmacy). To assess whether or not prevalence of patients in relation to drug use distribution changed overtime, adjusted prevalence ratios (PRs) was estimated with log-binomial regression models. Results: Among 2120 patients recruited in 27 wards continuously participating to data collection, 1882 were discharged alive and included in this analysis. The proportion of patients with very low drug use (0-1 drug) at hospital discharge increased overtime, from 2.7% in 2010 to 9.2% in 2016. Results from a log-logistic adjusted model confirmed the increasing PR of these very low drug users overtime (particularly in 2014 vs 2012, PR 1.83 95% CI 1.14-2.95). Moreover, from 2010 to 2016, there was an increasing number of patients who, on polypharmacy at hospital admission, abandoned it at hospital discharge, switching to the very low drug use group. Conclusion: This study shows that in internal medicine and geriatric wards continuously participating to the REgistro POliterapie Società Italiana di Medicina Interna register, the proportion of patients with a very low drug use at hospital discharge increased overtime, thus reducing the therapeutic burden in this at risk population.
2017
- Physical exercise for late life depression: effects on cognition and disability
[Articolo su rivista]
Neviani, Francesca; Belvederi Murri, Martino; Mussi, Chiara; Triolo, Federico; Toni, Giulio; Simoncini, Elisabetta; Tripi, Ferdinando; Menchetti, Marco; Ferrari, Silvia; Ceresini, Graziano; Cremonini, Alessandro; Bertolotti, Marco; Neri, Giovanni; Squatrito, Salvatore; Amore, Mario; Zanetidou, Stamatula; Neri, Mirco
abstract
Background:: Late-life depression is often associated with cognitive impairments and disability, which may persist even after adequate antidepressant drug treatment. Physical exercise is increasingly recognized as an effective antidepressant agent, and may exert positive effects on these features too. However, few studies examined this issue, especially by comparing different types of exercises. Methods:: We performed secondary analyses on data from the Safety and Efficacy of Exercise for Depression in Seniors study, a trial comparing the antidepressant effectiveness of sertraline (S), sertraline plus thrice-weekly non-progressive exercise (S+NPE), and sertraline plus thrice-weekly progressive aerobic exercise (S+PAE). Exercise was conducted in small groups and monitored by heart rate meters. Patients with late-life depression without severe cognitive impairment were recruited from primary care and assessed at baseline and 24 weeks, using the Montreal Cognitive Assessment (MOCA, total and subdomain scores) and Brief Disability Questionnaire. Analyses were based on Generalized Linear Models. Results:: In total, 121 patients (mean age 75, 71% females) were randomized to the study interventions. Compared with the S group, patients in the S+PAE group displayed greater improvements of MOCA total scores (p=0.006, effect size=0.37), visuospatial/executive functions (p=0.001, effect size=0.13), and disability (p=0.02, effect size=−0.31). Participants in the S+NPE group did not display significant differences with the control group. Conclusions:: Adding aerobic, progressive exercise to antidepressant drug treatment may offer significant advantages over standard treatment for cognitive abilities and disability. These findings suggest that even among older patients exercise may constitute a valid therapeutic measure to improve patients’ outcomes.
2017
- Prevalence and Determinants of the Use of Lipid-Lowering Agents in a Population of Older Hospitalized Patients: the Findings from the REPOSI (REgistro POliterapie Società Italiana di Medicina Interna) Study
[Articolo su rivista]
Bertolotti, Marco; Franchi, Carlotta; Rocchi, Marco Bruno; Miceli, Andrea; Libbra, Maria Vittoria; Nobili, Alessandro; Lancellotti, Giulia; Carulli, Lucia; Mussi, Chiara
abstract
BACKGROUND:
Older patients are prone to multimorbidity and polypharmacy, with an inherent risk of adverse events and drug interactions. To the best of our knowledge, available information on the appropriateness of lipid-lowering treatment is extremely limited.
AIM:
The aim of the present study was to quantify and characterize lipid-lowering drug use in a population of complex in-hospital older patients.
METHODS:
We analyzed data from 87 units of internal medicine or geriatric medicine in the REPOSI (Registro Politerapie della Società Italiana di Medicina Interna) study, with reference to the 2010 and 2012 patient cohorts. Lipid-lowering drug use was closely correlated with the clinical profiles, including multimorbidity markers and polypharmacy.
RESULTS:
2171 patients aged >65 years were enrolled (1057 males, 1114 females, mean age 78.6 years). The patients treated with lipid-lowering drugs amounted to 508 subjects (23.4%), with no gender difference. Atorvastatin (39.3%) and simvastatin (34.0%) were the most widely used statin drugs. Likelihood of treatment was associated with polypharmacy (≥5 drugs) and with higher Cumulative Illness Rating Scale (CIRS) score. At logistic regression analysis, the presence of coronary heart disease, peripheral vascular disease, and hypertension were significantly correlated with lipid-lowering drug use, whereas age showed an inverse correlation. Diabetes was not associated with drug treatment.
CONCLUSIONS:
In this in-hospital cohort, the use of lipid-lowering agents was mainly driven by patients' clinical history, most notably the presence of clinically overt manifestations of atherosclerosis. Increasing age seems to be associated with lower prescription rates. This might be indicative of cautious behavior towards a potentially toxic treatment regimen.
2017
- Prognostic value of degree and types of anaemia on clinical outcomes for hospitalised older patients
[Articolo su rivista]
Riva, E.; Colombo, R.; Moreo, G.; Mandelli, S.; Franchi, C.; Pasina, L.; Tettamanti, M.; Lucca, U.; Mannucci, P. M.; Nobili, A.; Perticone, F.; Salerno, F.; Corrao, S.; Marengoni, A.; Licata, G.; Violi, F.; Corazza, G. R.; Marcucci, M.; Eldin, T. K.; Di Blanca, M. P. D.; Djade, C. D.; Ardoino, I.; Cortesi, L.; Prisco, D.; Silvestri, E.; Cenci, C.; Emmi, G.; Biolo, G.; Guarnieri, G.; Zanetti, M.; Fernandes, G.; Vanoli, M.; Grignani, G.; Casella, G.; Bernardi, M.; Li Bassi, S.; Santi, L.; Zaccherini, G.; Mannarino, E.; Lupattelli, G.; Bianconi, V.; Paciullo, F.; Nuti, R.; Valenti, R.; Ruvio, M.; Cappelli, S.; Palazzuoli, A.; Salvatore, T.; Sasso, F. C.; Girelli, D.; Olivieri, O.; Matteazzi, T.; Barbagallo, M.; Plances, L.; Alcamo, R.; Licata, G.; Calvo, L.; Valenti, M.; Zoli, M.; Arno, R.; Pasini, F. L.; Capecchi, P. L.; Bicchi, M.; Palasciano, G.; Modeo, M. E.; Peragine, M.; Pappagallo, F.; Pugliese, S.; Di Gennaro, C.; Postiglione, A.; Barbella, M. R.; De Stefano, F.; Cappellini, M. D.; Fabio, G.; Seghezzi, S.; De Amicis, M. M.; Mari, D.; Rossi, P. D.; Damanti, S.; Ottolini, B. B.; Damanti, S.; Corazza, G. R.; Miceli, E.; Lenti, M. V.; Padula, D.; Murialdo, G.; Marra, A.; Cattaneo, F.; Secchi, M. B.; Ghelfi, D.; Anastasio, L.; Sofia, L.; Carbone, M.; Davi, G.; Guagnano, M. T.; Sestili, S.; Mancuso, G.; Calipari, D.; Bartone, M.; Meroni, M. R.; Perin, P. C.; Lorenzati, B.; Gruden, G.; Bruno, G.; Amione, C.; Fornengo, P.; Tassara, R.; Melis, D.; Rebella, L.; Delitala, G.; Pretti, V.; Masala, M. S.; Bolondi, L.; Rasciti, L.; Serio, I.; Fanelli, F. R.; Amoroso, A.; Molfino, A.; Petrillo, E.; Zuccala, G.; Franceschi, F.; De Marco, G.; Chiara, C.; Marta, S.; Romanelli, G.; Amolini, C.; Chiesa, D.; Marengoni, A.; Picardi, A.; Gentilucci, U. V.; Gallo, P.; Annoni, G.; Corsi, M.; Zazzetta, S.; Bellelli, G.; Arturi, F.; Succurro, E.; Rubino, M.; Sesti, G.; Loria, P.; Becchi, M. A.; Martucci, G.; Fantuzzi, A.; Maurantonio, M.; Delitala, G.; Carta, S.; Atzori, S.; Serra, M. G.; Bleve, M. A.; Gasbarrone, L.; Sajeva, M. R.; Brucato, A.; Ghidoni, S.; Di Corato, P.; Agnelli, G.; Marchesini, E.; Fabris, F.; Carlon, M.; Turatto, F.; Baritusso, A.; Turatto, F.; Manfredini, R.; Molino, C.; Pala, M.; Fabbian, F.; Boari, B.; De Giorgi, A.; Paolisso, G.; Rizzo, M. R.; Laieta, M. T.; Rini, G.; Mansueto, P.; Pepe, I.; Borghi, C.; Strocchi, E.; De Sando, V.; Sabba, C.; Vella, F. S.; Suppressa, P.; Valerio, R.; Pugliese, S.; Capobianco, C.; Fenoglio, L.; Bracco, C.; Giraudo, A. V.; Testa, E.; Serraino, C.; Fargion, S.; Bonara, P.; Periti, G.; Porzio, M.; Peyvandi, F.; Tedeschi, A.; Rossio, R.; Monzani, V.; Savojardo, V.; Folli, C.; Magnini, M.; Salerno, F.; Conca, A.; Gobbo, G.; Conca, A.; Balduini, C. L.; Bertolino, G.; Provini, S.; Quaglia, F.; Dallegri, F.; Ottonello, L.; Liberale, L.; Chin, W. S.; Carassale, L.; Caporotundo, S.; Traisci, G.; De Feudis, L.; Di Carlo, S.; Liberato, N. L.; Buratti, A.; Tognin, T.; Bianchi, G. B.; Giaquinto, S.; Purrello, F.; Di Pino, A.; Piro, S.; Rozzini, R.; Falanga, L.; Montrucchio, G.; Greco, E.; Tizzani, P.; Petitti, P.; Perciccante, A.; Coralli, A.; Salmi, R.; Gaudenzi, P.; Gamberini, S.; Semplicini, A.; Gottardo, L.; Vendemiale, G.; Serviddio, G.; Forlano, R.; Masala, C.; Mammarella, A.; Raparelli, V.; Violi, F.; Basili, S.; Perri, L.; Landolfi, R.; Montalto, M.; Mirijello, A.; Vallone, C.; Bellusci, M.; Setti, D.; Pedrazzoli, F.; Guasti, L.; Castiglioni, L.; Maresca, A.; Squizzato, A.; Molaro, M.; Bertolotti, M.; Mussi, C.; Libbra, M. V.; Miceli, A.; Pellegrini, E.; Carulli, L.; Perticone, F.; Sciacqua, A.; Quero, M.; Bagnato, C.; Corinaldesi, R.; De Giorgio, R.; Serra, M.; Grasso, V.; Ruggeri, E.; Salvi, A.; Leonardi, R.; Grassini, C.; Mascherona, I.; Minelli, G.; Maltese, F.; Gabrielli, A.; Mattioli, M.; Capeci, W.; Martino, G. P.; Corrao, S.; Messina, S.; Ghio, R.; Favorini, S.; Dal Col, A.; Minisola, S.; Colangelo, L.; Afeltra, A.; Alemanno, P.; Marigliano, B.; Castellino, P.; Blanco, J.; Zanoli, L.; Cattan
abstract
Study objective This study investigated in a large sample of in-patients the impact of mild-moderate-severe anaemia on clinical outcomes such as in-hospital mortality, re-admission, and death within three months after discharge. Methods A prospective multicentre observational study, involving older people admitted to 87 internal medicine and geriatric wards, was done in Italy between 2010 and 2012. The main clinical/laboratory data were obtained on admission and discharge. Based on haemoglobin (Hb), subjects were classified in three groups: group 1 with normal Hb, (reference group), group 2 with mildly reduced Hb (10.0–11.9 g/dL in women; 10.0–12.9 g/dL in men) and group 3 with moderately-severely reduced Hb (<10 g/dL in women and men). Results Patients (2678; mean age 79.2 ± 7.4 y) with anaemia (54.7%) were older, with greater functional impairment and more comorbidity. Multivariable analysis showed that mild but not moderate-severe anaemia was associated with a higher risk of hospital re-admission within three months (group 2: OR = 1.62; 95%CI 1.21–2.17). Anaemia failed to predict in-hospital mortality, while a higher risk of dying within three months was associated with the degree of Hb reduction on admission (group 2: OR = 1.82;95%CI 1.25–2.67; group 3: OR = 2.78;95%CI 1.82–4.26) and discharge (group 2: OR = 2.37;95%CI 1.48–3.93; group 3: OR = 3.70;95%CI 2.14–6.52). Normocytic and macrocytic, but not microcytic anaemia, were associated with adverse clinical outcomes. Conclusions Mild anaemia predicted hospital re-admission of older in-patients, while three-month mortality risk increased proportionally with anaemia severity. Type and severity of anaemia affected hospital re-admission and mortality, the worst prognosis being associated with normocytic and macrocytic anaemia.
2017
- The relationship between age and fat infiltration in liver and muscle
[Articolo su rivista]
Dondi, Giulia; Lancellotti, Giulia; Bertolotti, Marco; Mussi, Chiara
abstract
The relationship between sarcopenia and non-alcoholic fatty liver disease (NAFLD) is intriguing and extremely topical, when we consider the increasing prevalence of the manifestations of NAFLD and non-alcoholic steatohepatitis (NASH) worldwide, together with the overwhelming burden of aging-related disease conditions such as sarcopenia. Such an association was described mainly in Eastern Asian populations and different indices of fat infiltration, including computed tomography (CT) were utilized. On the other hand, the evidence in the industrialized countries of the Western world is rather limited. The present findings replicate the association between liver and muscle fat infiltration in an older Western population, and using a densitometric definition. Such an association suggests the presence of common pathogenic mechanisms in the two conditions, and among these insulin resistance might play a crucial role; nonetheless, in older populations the epidemiological pattern is likely more complex and diseases such as NAFLD and sarcopenia may not necessarily coexist in the same subject.
2016
- "Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool
[Articolo su rivista]
Bellelli, G.; Morandi, A.; Di Santo, S. G.; Mazzone, A.; Cherubini, A.; Mossello, E.; Bo, M.; Bianchetti, A.; Rozzini, R.; Zanetti, E.; Musicco, M.; Ferrari, A.; Ferrara, N.; Trabucchi, M.; Boffelli, S.; Stefano, F. D.; Filippi, F. D.; Guerini, F.; Bertoletti, E.; March, A.; Margiotta, A.; Mecocci, P.; Addesi, D.; Fanto, F.; Dijik, B.; Porrino, P.; Cotroneo, A. M.; Galli, G.; Bruni, A. C.; Bernardini, B.; Corsini, C.; Cagnin, A.; Zurlo, A.; Barbagallo, G.; Lunardelli, M. L.; Martini, E.; Battaglia, G.; Latella, R.; Petritola, D.; Sinforiani, E.; Cester, A.; Formilan, M.; Carbone, P.; Appollonio, I.; Cereda, D.; Tremolizzo, L.; Bottacchi, E.; Lucchetti, L.; Mariani, C.; Rapazzini, P.; Romanelli, G.; Marengoni, A.; Zuliani, G.; Bianchi, L.; Suardi, T.; Muti, E.; Bottura, R.; Sgro, G.; Mandas, A.; Serchisu, L.; Crippa, P.; Ivaldi, C.; Ungar, A.; Villani, D.; Raimondi, C.; Mussi, C.; Isaia, G.; Provenzano, G.; Mari, D.; Odetti, P.; Monacelli, F.; Incalzi, R. A.; Pluderi, A.; Bellamoli, C.; Terranova, L.; Scarpini, E.; D'Amico, G.; Cavallini, M. C.; Guerrini, G.; Scotuzzi, A. M.; Chiarello, A.; Pilotto, A.; Tognini, S.; Dell'Aquila, G.; Toigo, G.; Ceschia, G.; Piccinini, M.; Fabbo, A.; Zoli, M.; Forti, P.; Wenter, C.; Basile, G.; Lasagni, A.; Padovani, A.; Rozzini, L.; Cottino, M.; Vitali, S.; Tripi, G.; Avanzi, S.; Annoni, G.; Ruotolo, G.; Boschi, F.; Bonino, P.; Marchionni, N.; Fascendini, S.; Noro, G.; Turco, R.; Ubezio, M. C.; Serrati, C.; Infante, M.; Gentile, S.; Pernigotti, L. M.; Biagini, C. A.; Canonico, E.; Bonati, P.; Gareri, P.; Caffarra, P.; Ceretti, A.; Castiglia, R.; Gabelli, C.; Storto, M. L.; Putzu, P.; Santo, S. D.; Malara, A.; Spadea, F.; Di Cello, S.; Ceravolo, F.; Fabiano, F.; Rispoli, V.; Chiaradia, G.; Gabriele, A.; Settembrini, V.; Capomolla, D.; Citrino, A.; Scriva, A.; Bruno, I.; Secchi, R.; De Martino, E.; Muccinelli, R.; Lupi, G.; Paonessa, P.; Fabbri, A.; Castellari, S.; Po, A.; Gaggioli, G.; Varesi, M.; Moneti, P.; Capurso, S.; Latini, V.; Ghidotti, S.; Riccardelli, F.; Macchi, M.; Cassinadri, A.; Tonini, G.; Andreani, L.; Coralli, M.; Balotta, A.; Cancelliere, R.; Strazzacapa, M.; Cavallino, P.; Fabio, S.; De Filippi, F.; Giudice, C.; Floris, P.; Dentizzi, C.; D'Elia, K.; Azzini, M.; Cazzadori, M.; Benati, C.; Tobaldini, C.; Antonioli, A.; Mombelloni, P.; Fontanini, F.; Oliverio, M.; Del Grosso, L.; Giavedoni, C.; Bidoli, G.; Mazzei, B.; Corsonello, A.; Fusco, S.; Vena, S.; De Vuono, T.; Maiuri, G.; Castegnaro, E.; De Rosa, S.; Sechi, R. B.; Benvenuti, E.; Del Lungo, I.; Giardini, S.; Giulietti, C.; D'Amico, F.; Caronzolo, F.; Grippa, A.; Lombardo, G.; Pipicella, T.; Nitti, M. T.; Felici, A.; Pavan, S.; Lunelli, A.; Dimori, S.; Magnani, A.; Soglia, T.; Postacchini, D.; Brunelli, R.; Santini, S.; Francavilla, M.; Macchiati, I.; Sorvillo, F.; Giuli, C.; Perticone, F.; Rosa, P. C.; Bencardino, G.; Falbo, T.; Grillo, N.; Pezzilli, S.; Bergamo, D.; Furno, E.; Rrodhe, S.; Lucarini, S.; Dall'Acqua, F.; Cappelletto, F.; Calvani, D.; Becheri, D.; Gambardella, L.; Valente, C.; Ceci, G.; Ettorre, E.; Tironi, S.; Grassi, M. G.; Troisi, E.; Gabutto, A.; Baglietto, N.; Quazzo, L.; Rosatello, A.; Suraci, D.; Tagliabue, B.; Perrone, C.; Ferrara, L.; Castagna, A.; Tremolada, M.; Piano, S.; Serviddio, G.; Lo Buglio, A.; Gurrera, T.; Merlo, V.; Rovai, C.; Carlucci, R.; Abbaldo, A.; Monzani, F.; Qasem, A.; Bini, G.; Tafuto, S.; Mancuso, G.; Fragiacomo, F.; Pompanin, S.; Guerra, G.; Pala, M.; Menozzi, L.; Gatti, C. D.; Magon, S.; Di Francesco, V.; Faccioli, S.; Pellizzari, L.; Lia Lunardelli, M.; Macchiarulo, M.; Corneli, M.; Bacci, M.; Lo Storto, M.; Seresin, C.; Simonato, M.; Loreggian, M.; Cestonaro, F.; Durando, M.; Mazzoleni, M.; Russo, G.; Ponte, M.; Valchera, A.; Salustri, G.; Costa, A.; Cotta, M. R.; Pizio, R. N.; Perego, G.; Bucciantini, E.; Di Giovanni, M.; Franchi, F.; Claudio Mariani, S. B.; Grande, G.; Fugazza, L.; Guerrini, C.; De Paduanis, G.; Iallonardo, L.; Palumbo, P.; Ortolani, B.; Capatti, E.; Soavi, C
abstract
Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 ± 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys.
2016
- Adherence to antithrombotic therapy guidelines improves mortality among elderly patients with atrial fibrillation: insights from the REPOSI study
[Articolo su rivista]
Marco, Proietti; Alessandro, Nobili; Valeria, Raparelli; Laura, Napoleone; Pier Mannuccio, Mannucci; Gregory Y. H., Lip; On behalf of REPOSI, Investigators; Carulli, Lucia; Bertolotti, Marco; Mussi, Chiara
abstract
Atrial fibrillation (AF) is associated with a substantial risk of thromboembolism and mortality, significantly reduced by oral anticoagulation. Adherence to guidelines may lower the risks for both all cause and cardiovascular (CV) deaths. Methods: Our objective was to evaluate if antithrombotic prophylaxis according to the 2012 European Society of Cardiology (ESC) guidelines is associated to a lower rate of adverse outcomes. Data were obtained from REPOSI; a prospective observational study enrolling inpatients aged ≥65 years. Patients enrolled in 2012 and 2014 discharged with an AF diagnosis were analysed. Results: Among 2535 patients, 558 (22.0 %) were discharged with a diagnosis of AF. Based on ESC guidelines, 40.9 % of patients were on guideline-adherent thromboprophylaxis, 6.8 % were overtreated, and 52.3 % were undertreated. Logistic analysis showed that increasing age (p = 0.01), heart failure (p = 0.04), coronary artery disease (p = 0.013), peripheral arterial disease (p = 0.03) and concomitant cancer (p = 0.003) were associated with non-adherence to guidelines. Specifically, undertreatment was significantly associated with increasing age (p = 0.001) and cancer (p < 0.001), and inversely associated with HF (p = 0.023). AF patients who were guideline adherent had a lower rate of both all-cause death (p = 0.007) and CV death (p = 0.024) compared to those non-adherent. Kaplan–Meier analysis showed that guideline-adherent patients had a lower cumulative risk for both all-cause (p = 0.002) and CV deaths (p = 0.011). On Cox regression analysis, guideline adherence was independently associated with a lower risk of all-cause and CV deaths (p = 0.019 and p = 0.006). Conclusions: Non-adherence to guidelines is highly prevalent among elderly AF patients, despite guideline-adherent treatment being independently associated with lower risk of all-cause and CV deaths. Efforts to improve guideline adherence would lead to better outcomes for elderly AF patients
2016
- Bile acids and nonalcoholic fatty liver disease: An intriguing relationship
[Articolo su rivista]
Carulli, Lucia; Gabbi, Chiara; Bertolotti, Marco
abstract
Non-alcoholic fatty liver disease (NAFLD) stands nowadays as a leading cause of progressive impairment of liver function.
The role of bile acids in the modulation of hepatic lipid metabolism is interesting and controversial; previous evidence showed an inhibitory effect of bile acids on lipogenesis, which was attributed to the activation of the FXR-SHP axis and consequent depression of the LXRα-SREBP-1c lipogenic pathway. Evidence from our research group has shown that both exogenous administration of bile acids and endogenous exposure to bile acid overload (as in cholestasis) may reduce hepatic fat accumulation in rat models, although by different mechanisms.
The findings in the paper by Nagahashi et al are quite surprising, showing the development of fatty liver disease in SphK2 -/- mice, in association with a decreased expression of SREBP1c and lipogenic enzymes like FAS. The metabolic effects of bile acids on hepatic lipid metabolism seem to be strictly dependent on the experimental model utilized to induce fat liver accumulation, as well as on the modality of bile acid exposure (exogenous vs endogenous) and the relative activation of the LXR/FXR pathways.
Experimental evidence like that brought by Nagahashi et al1 may bring an enormous contribution in this field, in the perspective of novel pharmacological targets for the treatment of NAFLD.
2016
- HCV NS3 sequencing as a reliable and clinically useful tool for the assessment of genotype and resistance mutations for clinical samples with different HCV-RNA levels
[Articolo su rivista]
Di Maio, V. C.; Cento, V.; Di Paolo, D.; Aragri, M.; De Leonardis, F.; Tontodonati, M.; Micheli, V.; Bellocchi, M. C.; Antonucci, F. P.; Bertoli, A.; Lenci, I.; Milana, M.; Gianserra, L.; Melis, M.; Di Biagio, A.; Sarrecchia, C.; Sarmati, L.; Landonio, S.; Francioso, S.; Lambiase, L.; Nicolini, L. A.; Marenco, S.; Nosotti, L.; Giannelli, V.; Siciliano, M.; Romagnoli, Dante; Pellicelli, A.; Vecchiet, J.; Magni, C. F.; Babudieri, S.; Mura, M. S.; Taliani, G.; Mastroianni, C.; Vespasiani Gentilucci, U.; Romano, M.; Morisco, F.; Gasbarrini, A.; Vullo, V.; Bruno, S.; Baiguera, C.; Pasquazzi, C.; Tisone, G.; Picciotto, A.; Andreoni, M.; Parruti, G.; Rizzardini, G.; Angelico, M.; Perno, C. F.; Ceccherini Silberstein, F; Mariani, R.; Paoloni, M.; Iapadre, N.; Grimaldi, A.; Menzaghi, B.; Quirino, T.; Vecchiet, J.; Bruzzone, B.; De Maria, A.; Di Biagio, A.; Marenco, S.; Picciotto, A.; Viscoli, C.; Casinelli, K.; Delle Monache, M.; Lichtner, M.; Mastroianni, C.; Aghemo, A.; Bruno, S.; Cerrone, M.; Colombo, M.; D'Arminio Monforte, A.; Danieli, E.; Donato, F.; Gubertini, G.; Landonio, S.; Magni, C. F.; Mancon, A.; Micheli, V.; Monico, S.; Niero, F.; Puoti, M.; Rizzardini, G.; Russo, M. L.; Alfieri, R.; Gnocchi, M.; Orro, A.; Milanesi, L.; Baldelli, Enrica; Bertolotti, Marco; Borghi, Valentina; Mussini, C.; Romagnoli, D.; Brancaccio, G.; Caporaso, N.; Gaeta, G. B.; Lembo, V.; Morisco, F.; Calvaruso, V.; Craxí, A.; Di Marco, V.; Mazzola, A.; Petta, S.; D'Amico, E.; Cacciatore, P.; Consorte, A.; Pace Palitti, V.; Parruti, G.; Pieri, A.; Polilli, E.; Tontodonati, M.; Andreoni, M.; Angelico, M.; Antenucci, F.; Antonucci, F. P.; Aragri, M.; Armenia, D.; Baiocchi, L.; Bellocchi, M.; Biliotti, E.; Biolato, M.; Carioti, L.; Ceccherini Silberstein, F.; Cento, V.; Cerasari, G.; Cerva, C.; Ciotti, M.; D'Ambrosio, C.; D'Ettorre, G.; De Leonardis, F.; De Sanctis, A.; Di Maio, V. C.; Di Paolo, D.; Francioso, S.; Furlan, C.; Gallo, P.; Gasbarrini, A.; Giannelli, V.; Gianserra, L.; Grieco, A.; Grieco, S.; Lambiase, L.; Lattanzi, B.; Lenci, I.; Malagnino, V.; Manuelli, M.; Merli, M.; Miglioresi, L.; Milana, M.; Nosotti, L.; Palazzo, D.; Pasquazzi, C.; Pellicelli, A.; Perno, C. F.; Romano, M.; Santopaolo, F.; Santoro, M. M.; Sarmati, L.; Sarrecchia, C.; Sforza, D.; Siciliano, M.; Sorbo, M. C.; Spaziante, M.; Svicher, V.; Taliani, G.; Teti, E.; Tisone, G.; Vullo, V.; Mangia, A.; Babudieri, S.; Maida, I.; Melis, M.; Mura, M. S.; Falconi, L.; Di Giammartino, D.; Tarquini, P.
abstract
Objectives: This study aims to evaluate the reliability and clinical utility of NS3 sequencing in hepatitis C virus (HCV) 1-infected patients who were candidates to start a PI-containing regimen. Methods: NS3 protease sequencing was performed by in-house-developed HCV-1 subtype-specific protocols. Phylogenetic analysis was used to test sequencing reliability and concordance with previous genotype/subtype assignment by commercial genotyping assays. Results: Five hundred and sixty-seven HCV plasma samples with quantifiable HCV-RNA from 326 HCV-infected patients were collected between 2011 and 2014. Overall, the success rate of NS3 sequencing was 88.9%. The success rate between the two subtype protocols (HCV-1a/HCV-1b) was similarly high for samples with HCV-RNA > 3 log IU/mL (>92% success rate), while it was slightly lower for HCV-1a samples with HCV-RNA ≤ 3 log IU/mL compared with HCV-1b samples. Phylogenetic analysis confirmed the genotype/subtype given by commercial genotyping assays in 92.9% (303/326) of cases analysed. In the remaining 23 cases (7.1%), 1 was HCV-1g (previously defined as subtype 1a), 1 was HCV-4d (previously defined as genotype 1b) and 1 was HCV-1b (previously defined as genotype 2a/2c). In the other cases, NS3 sequencing precisely resolved the either previous undetermined/discordant subtype 1 or double genotype/subtype assignment by commercial genotyping assays. Resistance-associated variants (RAVs) to PI were detected in 31.0% of samples. This prevalence changed according to PI experience (17.1% in PI-naive patients versus 79.2% in boceprevir/telaprevir/simeprevir-failing patients). Among 96 patients with available virological outcome following boceprevir/telaprevir treatment, a trend of association between baseline NS3 RAVs and virological failure was observed (particularly for HCV-1a-infected patients: 3/21 failing patients versus 0/22 achieving sustained virological response; P = 0.11). Conclusions: HCV-NS3 sequencing provides reliable results and at the same time gives two clinically relevant pieces of information: A correct subtype/genotype assignment and the detection of variants that may interfere with the efficacy of PI.
2016
- Liver X receptors and copper metabolism: New frontiers for the oxysterol receptors
[Articolo su rivista]
Gabbi, Chiara; Bertolotti, Marco
abstract
Treatment with Liver X Receptor (LXR) agonists ameliorates disease manifestation in a mouse model of Wilson disease (WD) but only with a partial effect in inducing the predicted LXR target genes. These studies open new perspective for the oxysterols recptors LXR, involved not only in controlling lipid metabolism, inflammation, water transport and cell proliferation but also in regulating copper homeostasis.
2016
- Telomere length elongation after weight loss intervention in obese adults
[Articolo su rivista]
Carulli, Lucia; Anzivino, Claudia; Baldelli, Enrica; Zenobii, Mf; Rocchi, Mb; Bertolotti, Marco
abstract
INTRODUCTION:
Telomeres may be considered markers of biological aging, shorter telomere length is associated with some age-related diseases; in several studies short telomere length has also been associated to obesity in adults and adolescents. However the relationship between telomere complex functions and obesity is still not clear. Aim of the study was to assess telomere length (TL) in adults' obese subjects before and after weight loss obtained by placement of bioenteric intragastric balloon (BIB) for 6months.
METHODS:
We enrolled 42 obese subjects before and after BIB placement as weight loss intervention. Blood samples were collected in order to obtain DNA from leukocyte to measure TL by quantitative PCR.
RESULTS:
Data were analyzed only in 37 subjects with complete data; all presented important body weight loss (124.06±26.7 vs 105.40±23.14, p<0.001) and more interesting they presented a significant increase in TL (3.58±0.83 vs 5.61±3.29, p<0.001). Moreover we observed a significant positive correlation between TL elongation and weight loss (r=0.44, p=0.007) as well as an inverse correlation between TL at baseline and TL elongation (r=-0.35, p=0.03).The predictors of TL elongation were once again weight loss and short TL at baseline (respectively p=0.007 and p=0.003).
CONCLUSIONS:
Our study shows that weight loss is associated to telomere lengthening in a positive correlation: the greater weight loss the greater telomere lengthening; moreover telomere lengthening is more significant in those subjects with shortest telomeres at baseline.
2015
- Adherence to antibiotic treatment guidelines and outcomes in the hospitalized elderly with different types of pneumonia
[Articolo su rivista]
Rossio, Raffaella; Franchi, Carlotta; Ardoino, Ilaria; Djade, Codjo D.; Tettamanti, Mauro; Pasina, Luca; Salerno, Francesco; Marengoni, Alessandra; Corrao, Salvatore; Marcucci, Maura; Peyvandi, Flora; Biganzoli, Elia M.; Nobili, Alessandro; Mannucci, Pier Mannuccio; Sparacio, Eleonora; Alborghetti, Stefania; Di Costanzo, Rosa; Prisco, Domenico; Silvestri, Elena; Cenci, Caterina; Barnini, Tommaso; Delitala, Giuseppe; Carta, Stefano; Atzori, Sebastiana; Guarnieri, Gianfranco; Zanetti, Michela; Spalluti, Annalisa; Serra, Maria Grazia; Bleve, Maria Antonietta; Vanoli, Massimo; Grignani, Giulia; Casella, Gianluca; Gasbarrone, Laura; Maniscalco, Giorgio; Gunelli, Massimo; Tirotta, Daniela; Brucato, Antonio; Ghidoni, Silvia; Di Corato, Paola; Bernardi, Mauro; Li Bassi, Silvia; Santi, Luca; Agnelli, Giancarlo; Iorio, Alfonso; Marchesini, Emanuela; Mannarino, Elmo; Lupattelli, Graziana; Rondelli, Pamela; Paciullo, Francesco; Fabris, Fabrizio; Carlon, Michela; Turatto, Francesca; Baroni, Maria Cristina; Zardo, Marianna; Manfredini, Roberto; Molino, Christian; Pala, Marco; Fabbian, Fabio; Nuti, Ranuccio; Valenti, Roberto; Ruvio, Martina; Cappelli, Silvia; Paolisso, Giuseppe; Rizzo, Maria Rosaria; Laieta, Maria Teresa; Salvatore, Teresa; Sasso, Ferdinando Carlo; Utili, Riccardo; Mangoni, Emanuele Durante; Pinto, Daniela; Olivieri, Oliviero; Stanzial, Anna Maria; Fellin, Renato; Volpato, Stefano; Fotini, Sioulis; Barbagallo, Mario; Dominguez, Ligia; Plances, Lidia; D'Angelo, Daniela; Rini, Giovanbattista; Mansueto, Pasquale; Pepe, Ilenia; Licata, Giuseppe; Calvo, Luigi; Valenti, Maria; Borghi, Claudio; Strocchi, Enrico; Rinaldi, Elisa Rebecca; Zoli, Marco; Fabbri, Elisa; Magalotti, Donatella; Auteri, Alberto; Pasqui, Anna Laura; Puccetti, Luca; Pasini, Franco Laghi; Capecchi, Pier Leopoldo; Bicchi, Maurizio; Sabbà, Carlo; Vella, Francesco Saverio; Marseglia, Alessandro; Luglio, Chiara Valentina; Palasciano, Giuseppe; Modeo, Maria Ester; Aquilino, Annamaria; Raffaele, Pallante; Pugliese, Stefania; Capobianco, Caterina; Postiglione, Alfredo; Barbella, Maria Rosaria; De Stefano, Francesco; Fenoglio, Luigi; Brignone, Chiara; Bracco, Christian; Giraudo, Alessia; Musca, Giuseppe; Cuccurullo, Olga; Cricco, Luigi; Fiorentini, Alessandra; Cappellini, Maria Domenica; Fabio, Giovanna; Seghezzi, Sonia; De Amicis, Margherita Migone; Fargion, Silvia; Bonara, Paola; Bulgheroni, Mara; Lombardi, Rosa; Magrini, Fabio; Massari, Ferdinando; Tonella, Tatiana; Tedeschi, Alberto; Moreo, Guido; Ferrari, Barbara; Roncari, Luisa; Monzani, Valter; Savojardo, Valeria; Folli, Christian; Magnini, Maria; Mari, Daniela; Rossi, Paolo Dionigi; Damanti, Sarah; Prolo, Silvia; Lilleri, Maria Sole; Micale, Giuliana; Podda, Mauro; Selmi, Carlo; Meda, Francesca; Accordino, Silvia; Conca, Alessio; Monti, Valentina; Corazza, Gino Roberto; Miceli, Emanuela; Lenti, Marco Vincenzo; Padula, Donatella; Balduini, Carlo L.; Bertolino, Giampiera; Provini, Stella; Quaglia, Federica; Murialdo, Giovanni; Bovio, Marta; Dallegri, Franco; Ottonello, Luciano; Quercioli, Alessandra; Barreca, Alessandra; Secchi, Maria Beatrice; Ghelfi, Davide; Chin, Wu Sheng; Carassale, Laura; Caporotundo, Silvia; Anastasio, Luigi; Sofia, Lucia; Carbone, Maria; Traisci, Giancarlo; De Feudis, Lucrezia; Di Carlo, Silvia; Davì, Giovanni; Guagnano, Maria Teresa; Sestili, Simona; Bergami, Elisabetta; Rizzioli, Emanuela; Cagnoni, Carlo; Bertone, Luca; Manucra, Antonio; Buratti, Alberto; Tognin, Tiziana; Liberato, Nicola Lucio; Bernasconi, Giordano; Nardo, Barbara; Bianchi, Giovanni Battista; Benetti, Giampiero; Quagliolo, Michela; Centenaro, Giuseppe Riccardo; Purrello, Francesco; Di Pino, Antonino; Piro, Salvatore; Mancuso, Gerardo; Calipari, Daniela; Bartone, Mosè; Gullo, Francesco; Cortellaro, Michele; Magenta, Marina; Perego, Francesca; Meroni, Maria Rachele; Cicardi, Marco; Magenta, Antonio Gidaro Marina; Sacco, Andrea; Bonelli, Antonio; Dentamaro, Gaetano; Rozzini,
abstract
Background: Few studies evaluated the clinical outcomes of Community Acquired Pneumonia (CAP), Hospital-Acquired Pneumonia (HAP) and Health Care-Associated Pneumonia (HCAP) in relation to the adherence of antibiotic treatment to the guidelines of the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) in hospitalized elderly people (65 years or older). Methods: Data were obtained from REPOSI, a prospective registry held in 87 Italian internal medicine and geriatric wards. Patients with a diagnosis of pneumonia (ICD-9 480-487) or prescribed with an antibiotic for pneumonia as indication were selected. The empirical antibiotic regimen was defined to be adherent to guidelines if concordant with the treatment regimens recommended by IDSA/ATS for CAP, HAP, and HCAP. Outcomes were assessed by logistic regression models. Results: A diagnosis of pneumonia was made in 317 patients. Only 38.8% of them received an empirical antibiotic regimen that was adherent to guidelines. However, no significant association was found between adherence to guidelines and outcomes. Having HAP, older age, and higher CIRS severity index were the main factors associated with in-hospital mortality. Conclusions: The adherence to antibiotic treatment guidelines was poor, particularly for HAP and HCAP, suggesting the need for more adherence to the optimal management of antibiotics in the elderly with pneumonia.
2015
- Frequency of left ventricular hypertrophy in non-valvular atrial fibrillation
[Articolo su rivista]
Proietti, M.; Marra, A. M.; Tassone, E. J.; de Vuono, S.; Corrao, S.; Gobbi, P.; Perticone, F.; Corazza, G. R.; Basili, S.; Lip, G. Y. H.; Violi, F.; Raparelli, V.; Alessandri, C.; Serviddio, G.; Fascetti, S.; Serra, P.; Palange, P.; Greco, E.; Bruno, G.; Averna, M.; Giammanco, A.; Sposito, P.; de Cristofaro, R.; de Gennaro, L.; Loria, P.; Pellegrini, E.; Cominacini, L.; Mozzini, C.; Sprovieri, M.; Spagnuolo, V.; Cerqua, G.; Cerasola, G.; Mule, G.; Barbagallo, M.; Lo Sciuto, S.; Monteverde, A.; Saitta, A.; Lo Gullo, A.; Malatino, L.; Cilia, C.; Licata, G.; Tuttolomondo, A.; Conigliaro, R.; Pinto, A.; Di Raimondo, D.; Signorelli, S.; Anzaldi, M.; de Palma, D.; Galderisi, M.; Cudemo, G.; Galletti, F.; Fazio, V.; de Luca, N.; Meccariello, A.; Caputo, D.; de Donato, M. T.; Iannuzi, A.; Bresciani, A.; Giunta, R.; Cimini, C.; Durante, M. E.; Agrusta, F.; Iorio, F.; Adinolfi, L. E.; Sellitto, A.; Restivo, L.; Bellis, P.; Tirelli, P.; Sacerdoti, D.; Pesce, P.; Vanni, D.; Iuliano, L.; Ciacciarelli, M.; Pacelli, A.; Palazzuoli, A.; Cacciafesta, M.; Gueli, N.; Capeci, W.; Tarquinio, N.; Pellegrini, F.; Vincentelli, G. M.; Ravallese, F.; Santini, C.; Letizia, C.; Petramala, L.; Zinnamosca, L.; Cilli, M.; Savoriti, C.; Falaschi, P.; Martocchia, A.; Stefanelli, M.; Marigliano, V.; Lo Iacono, C.; Brusco, S.; Bertazzoni, G.; Attalla El Halabieh, E.; Paradiso, M.; Lizzi, E. M.; Timmi, S.; Battisti, P.; Cerci, S.; Ciavolella, M.; Di Veroli, C.; Malci, F.; de Ciocchis, A.; Abate, D.; Castellino, P.; Curto, I.; Vecchio, C. R.; Mannarino, E.; Pasqualini, L.; Fattori, C.; Pende, A.; Denegri, A.; Artom, N.; Ricchio, R.; Fimognari, F. L.; Alletto, M.; Messina, S.; Sesti, G.; Arturi, F.; Grembiale, A.; Maio, R.; Scarpino, P. E.; Carullo, G.; Sciacqua, A.; Frugiuele, P.; Battaglia, G.; Vidili, G.; Atzori, S.; Delitala, G.; Davi, G.; Angelucci, E.; Sestili, S.; Traisci, G.; de Feudis, L.; Di Michele, D.; Fava, A.; Balsano, C.; de Ciantis, P.; Desideri, G.; Camerota, A.; Migliacci, R.; Porciello, G.; Mezzetti, M.; Gresele, P.; Vedovati, C.; Fierro, T.; Puccetti, L.; Scarpini, F.; Bertolotti, M.; Mussi, C.; Boddi, M.; Savino, A.; Contri, S.; Saller, A.; Fabris, F.; Pesavento, R.; Filippi, L.; Vedovetto, V.; Puato, M.; Treleani, M.; de Luca, E.; de Zaiacomo, F.; Giantin, V.; Semplicini, A.; Minuz, P.; Calabria, S.; Romano, S.; Fantin, F.; Manica, A.; Stockner, I.; Pattis, P.; Gutmann, B.; Catena, C.; Colussi, G.; Annoni, G.; Bruni, A. A.; Castagna, A.; Spinelli, D.; Miceli, E.; Padula, D.; Schinco, G.; Spreafico, S.; Secchi, B.; Vanoli, M.; Casella, G.; Serra, M. G.; Longo, S.; Antonaci, S.; Belfiore, A.; Ricci, L.; Ventrella, F.; Iamele, L.; Bianco, C.; Santovito, D.; Cipollone, F.; Nicolai, S.; Salvati, F.; Rini, G. B.; Scozzari, F.; Muiesan, M. L.; Salvetti, M.; Bazza, A.; Picardi, A.; de Vincentis, A.; Cosio, P.; Terzolo, M.; Madaffari, B.; Parasporo, B.; Fenoglio, L.; Bracco, C.; Melchio, R.; Gentili, T.; Salvi, A.; Nitti, C.; Falsetti, L.; Gabrielli, A.; Paglione, I.; Capucci, A.; Brambatti, M.; Sparagna, A.; Tirotta, D.; Andreozzi, P.; Ettorre, E.; Viscogliosi, G.; Rossi, F. F.; Delfino, M.; Glorioso, N.; Melis, G.; Marras, G.; Matta, M.; Sacco, A.; Stellitano, E.; Scordo, A.; Russo, F.; Caruso, A. A.; Porreca, E.; Santilli, F.; Tana, M.; Ferri, C.; Grassi, D.; Cheli, P.; Portincasa, P.; Muscianisi, G.; Giordani, S.; Stanghellini, V.; Sabba, C.; Suppressa, P.; Mancuso, G.; Bartone, M.; Calipari, D.; Arcidiacono, G.; Bellanuova, I.; Ferraro, M.; Scalzo, A.; Marigliano, G.; Cozzolino, D.; Lampitella, A.; Acri, V.; Galasso, D.; Mazzei, F.; Galasso, S.; Buratti, A.; Porta, M.; Brizzi, M. F.; Fattorini, A.; Sampietro, F.; D'Angelo, A.; Pala, M.; Fabbian, F.; Manfredini, R.; Moroni, C.; Valente, L.; Lopreiato, F.; Parente, F.; Granata, M.; Moia, M.; Braham, S.; Rossi, M.; Pesce, M.; Gentile, A.; Catozzo, V.; Di Napoli, M.; Baciarello, G.; Rancan, E.; Ageno, W.; Guasti, L.; Ciccaglioni, A.; Negri, S.; Polselli, M.; Abbate, R.; Marcucci, R.; Cangemi, R.; Pi
abstract
Left ventricular hypertrophy (LVH) is significantly related to adverse clinical outcomes in patients at high risk of cardiovascular events. In patients with atrial fibrillation (AF), data on LVH, that is, prevalence and determinants, are inconsistent mainly because of different definitions and heterogeneity of study populations. We determined echocardiographic-based LVH prevalence and clinical factors independently associated with its development in a prospective cohort of patients with non-valvular (NV) AF. From the "Atrial Fibrillation Registry for Ankle-brachial Index Prevalence Assessment: Collaborative Italian Study" (ARAPACIS) population, 1,184 patients with NVAF (mean age 72 ± 11 years; 56% men) with complete data to define LVH were selected. ARAPACIS is a multicenter, observational, prospective, longitudinal on-going study designed to estimate prevalence of peripheral artery disease in patients with NVAF. We found a high prevalence of LVH (52%) in patients with NVAF. Compared to those without LVH, patients with AF with LVH were older and had a higher prevalence of hypertension, diabetes, and previous myocardial infarction (MI). A higher prevalence of ankle-brachial index ≤0.90 was seen in patients with LVH (22 vs 17%, p = 0.0392). Patients with LVH were at significantly higher thromboembolic risk, with CHA2DS2-VASc ≥2 seen in 93% of LVH and in 73% of patients without LVH (p <0.05). Women with LVH had a higher prevalence of concentric hypertrophy than men (46% vs 29%, p = 0.0003). Logistic regression analysis demonstrated that female gender (odds ratio [OR] 2.80, p <0.0001), age (OR 1.03 per year, p <0.001), hypertension (OR 2.30, p <0.001), diabetes (OR 1.62, p = 0.004), and previous MI (OR 1.96, p = 0.001) were independently associated with LVH. In conclusion, patients with NVAF have a high prevalence of LVH, which is related to female gender, older age, hypertension, and previous MI. These patients are at high thromboembolic risk and deserve a holistic approach to cardiovascular prevention.
2015
- Lights and shadows in the management of old and new oral anticoagulants in the real world of atrial fibrillation by Italian internists. A survey from the Atrial Fibrillation Registry for Ankle-Brachial Index Prevalence Assessment-Collaborative Italian Study
[Articolo su rivista]
Pignatelli, P.; Pastori, D.; Perticone, F.; Corazza, G. R.; Violi, F.; Cominacini, L.; Mozzini, C.; De Palma, D.; Galderisi, M.; Cudemo, G.; Galletti, F.; Fazio, V.; Adinolfi, L. E.; Sellitto, A.; Restivo, L.; Cacciafesta, M.; Gueli, N.; Castellino, P.; Curto, I.; Vecchio, C.; Sesti, G.; Arturi, F.; Grembiale, A.; Scarpino, P. E.; Carullo, G.; Vidili, G.; Atzori, S.; Delitala, G.; Di Michele, D.; Fava, A.; Bertolotti, M.; Mussi, C.; De Luca, E.; De Zaiacomo, F.; Giantin, V.; Miceli, E.; Padula, D.; Santovito, D.; Cipollone, F.; Andreozzi, P.; Ettorre, E.; Viscogliosi, G.; Glorioso, N.; Melis, G.; Marras, G.; Matta, M.; Porta, M.; Brizzi, M. F.; Moroni, C.; Valente, L.; Lopreiato, F.; Gentile, A.; Catozzo, V.; Rancan, E.; Ageno, W.; Guasti, L.; Cangemi, R.; Pignataro, F. S.; Ferro, D.; Loffredo, L.; Perri, L.; Catasca, E.; Raparelli, V.; Napoleone, L.; Bucci, T.; Baratta, F.; Talerico, G.; Calvieri, C.; Vicario, T.; Russo, R.; Saliola, M.; Del Ben, M.; Angelico, F.; Vestri, A. R.; Farcomeni, A.; Di Tanna, G.; Davi', G.; Basili, S.; Mannucci, P. M.; Lip, G. Y.; Hiatt, W.; Licata, G.; Gobbi, P.; Corrao, S.
abstract
The lights and shadows in the management of old and new oral anticoagulants are described in the real world of atrial fibrillation by Italian internists.
2015
- Sofosbuvir-based therapy cures hepatitis C virus infection after prior treatment failures in a patient with concurrent lymphoma
[Articolo su rivista]
Romagnoli, Dante; Marrazzo, Alessandra; Ballestri, Stefano; Lonardo, Amedeo; Bertolotti, Marco
abstract
We report on the first well-tolerated and successful use of sofosbuvir-based therapy in a patient in whom chronic infection with hepatitis C had preceded the development of B-cell non-Hodgkin's lymphoma. The patient had previously failed numerous attempts to clear the hepatitis C virus with traditional antiviral schedules. We demonstrate that sofosbuvir-based therapy resulted in cure of hepatitis C in a patient who had relapsed during combination therapy with an NS5A inhibitor, an NS3 protease inhibitor and ribavirin, as well as treatment failures to multiple courses of interferon-based therapy. This report also suggests that eradication of hepatitis C virus may result in the short-term prevention of B-cell non-Hodgkin's lymphoma relapse. The findings from our case require further validation in future cohorts of patients.
2014
- Age-associated alterations in cholesterol homeostasis: evidence from a cross-sectional study in a Northern Italy population.
[Articolo su rivista]
Bertolotti, Marco; Mussi, Chiara; Pellegrini, E; Magni, A; Del Puppo, M; Ognibene, Silvia; Carulli, Lucia; Anzivino, C; Baldelli, Enrica; Loria, Paola; Carulli, N.
abstract
BACKGROUND:
The modifications of cholesterol metabolism associated with aging are ill-defined. The objective of this study was to define age-associated alterations of the different metabolic pathways controlling cholesterol homeostasis by analyzing circulating sterols.
METHODS:
We analyzed serum samples collected from 201 adult (75 male, 126 female) subjects within the epidemiological MICOL study (Multicentrica Italiana Colelitiasi). The age range was 38-79 years; 103 had evidence of gallstones. The concentrations of the different sterols, recognized as markers of the main pathways of cholesterol homeostasis, were analyzed by gas chromatography-mass spectrometry, including lathosterol (synthesis), campesterol and sitosterol (absorption), and 7α-hydroxy-4-cholesten-3-one (degradation to bile acids).
RESULTS:
A significant direct correlation was detected between age and cholesterol levels (r =0.34, P<0.01). The lathosterol/cholesterol ratio was lower in older age quartiles (P<0.05 by analysis of variance), with an inverse correlation between the lathosterol/cholesterol ratio and age (r=-0.32, P<0.01). Such correlation was particularly evident in females. The campesterol/cholesterol and sitosterol/cholesterol ratios were inversely correlated with aging in control, but not in gallstone patients. The levels of 7α-hydroxy-4-cholesten-3-one were not correlated with age.
CONCLUSION:
These data show a reduction of cholesterol synthesis with aging which is associated with increased circulating cholesterol levels. The finding might be related to a reduced metabolic need for cholesterol in advancing age, leading to a downregulation of the main mechanisms of cholesterol intake in the liver. A different age-related behavior was observed in gallstone-free versus gallstone patients regarding cholesterol absorption. The possible implications in terms of the pharmacological management of hypercholesterolemia in the elderly remain to be defined.
2014
- Diabete materno e rischio di macrosomia fetale: uno studio di coorte nella regione Emilia-Romagna.
[Abstract in Atti di Convegno]
Malagoli, Carlotta; Filippini, Tommaso; Rodolfi, R; Bertolotti, Marco; Astolfi, G; Calzolari, E; Puccini, A; Martini, M; Nicolini, F; Vinceti, Marco
abstract
.
2014
- Gender-differences in disease distribution and outcome in hospitalized elderly: Data from the REPOSI study
[Articolo su rivista]
Corrao, S.; Santalucia, P.; Argano, C.; Djade, C. D.; Barone, E.; Tettamanti, M.; Pasina, L.; Franchi, C.; Kamal Eldin, T.; Marengoni, A.; Salerno, F.; Marcucci, M.; Mannucci, P. M.; Nobili, A.; Sparacio, Eleonora; Alborghetti, Stefania; Di Costanzo, Rosa; Prisco, Domenico; Silvestri, Elena; Cenci, Caterina; Barnini, Tommaso; Delitala, Giuseppe; Carta, Stefano; Atzori, Sebastiana; Guarnieri, Gianfranco; Zanetti, Michela; Spalluti, Annalisa; Serra, Maria Grazia; Bleve, Maria Antonietta; Vanoli, Massimo; Grignani, Giulia; Casella, Gianluca; Gasbarrone, Laura; Maniscalco, Giorgio; Gunelli, Massimo; Tirotta, Daniela; Brucato, Antonio; Ghidoni, Silvia; Di Corato, Paola; Bernardi, Mauro; Li Bassi, Silvia; Santi, Luca; Agnelli, Giancarlo; Iorio, Alfonso; Marchesini, Emanuela; Mannarino, Elmo; Lupattelli, Graziana; Rondelli, Pamela; Paciullo, Francesco; Fabris, Fabrizio; Carlon, Michela; Turatto, Francesca; Baroni, Maria Cristina; Zardo, Marianna; Manfredini, Roberto; Molino, Christian; Pala, Marco; Fabbian, Fabio; Nuti, Ranuccio; Valenti, Roberto; Ruvio, Martina; Cappelli, Silvia; Paolisso, Giuseppe; Rizzo, Maria Rosaria; Laieta, Maria Teresa; Salvatore, Teresa; Sasso, Ferdinando Carlo; Utili, Riccardo; Mangoni, Emanuele Durante; Pinto, Daniela; Olivieri, Oliviero; Stanzial, Anna Maria; Fellin, Renato; Volpato, Stefano; Fotini, Sioulis; Barbagallo, Mario; Dominguez, Ligia; Plances, Lidia; D'Angelo, Daniela; Rini, Giovanbattista; Mansueto, Pasquale; Pepe, Ilenia; Licata, Giuseppe; Calvo, Luigi; Valenti, Maria; Borghi, Claudio; Strocchi, Enrico; Rinaldi, Elisa Rebecca; Zoli, Marco; Fabbri, Elisa; Magalotti, Donatella; Auteri, Alberto; Pasqui, Anna Laura; Puccetti, Luca; Pasini, Franco Laghi; Capecchi, Pier Leopoldo; Bicchi, Maurizio; Sabbà, Carlo; Vella, Francesco Saverio; Marseglia, Alessandro; Luglio, Chiara Valentina; Palasciano, Giuseppe; Modeo, Maria Ester; Aquilino, Annamaria; Raffaele, Pallante; Pugliese, Stefania; Capobianco, Caterina; Postiglione, Alfredo; Barbella, Maria Rosaria; De Stefano, Francesco; Fenoglio, Luigi; Brignone, Chiara; Bracco, Christian; Giraudo, Alessia; Musca, Giuseppe; Cuccurullo, Olga; Cricco, Luigi; Fiorentini, Alessandra; Cappellini, Maria Domenica; Fabio, Giovanna; Seghezzi, Sonia; De Amicis, Margherita Migone; Fargion, Silvia; Bonara, Paola; Bulgheroni, Mara; Lombardi, Rosa; Magrini, Fabio; Massari, Ferdinando; Tonella, Tatiana; Peyvandi, Flora; Tedeschi, Alberto; Rossio, Raffaella; Moreo, Guido; Ferrari, Barbara; Roncari, Luisa; Monzani, Valter; Savojardo, Valeria; Folli, Christian; Magnini, Maria; Mari, Daniela; Rossi, Paolo Dionigi; Damanti, Sarah; Prolo, Silvia; Lilleri, Maria Sole; Micale, Giuliana; Podda, Mauro; Selmi, Carlo; Meda, Francesca; Accordino, Silvia; Conca, Alessio; Monti, Valentina; Corazza, Gino Roberto; Miceli, Emanuela; Lenti, Marco Vincenzo; Padula, Donatella; Balduini, Carlo L.; Bertolino, Giampiera; Provini, Stella; Quaglia, Federica; Murialdo, Giovanni; Bovio, Marta; Dallegri, Franco; Ottonello, Luciano; Quercioli, Alessandra; Barreca, Alessandra; Secchi, Maria Beatrice; Ghelfi, Davide; Chin, Wu Sheng; Carassale, Laura; Caporotundo, Silvia; Anastasio, Luigi; Sofia, Lucia; Carbone, Maria; Traisci, Giancarlo; De Feudis, Lucrezia; Di Carlo, Silvia; Davì, Giovanni; Guagnano, Maria Teresa; Sestili, Simona; Bergami, Elisabetta; Rizzioli, Emanuela; Cagnoni, Carlo; Bertone, Luca; Manucra, Antonio; Buratti, Alberto; Tognin, Tiziana; Liberato, Nicola Lucio; Bernasconi, Giordano; Nardo, Barbara; Bianchi, Giovanni Battista; Benetti, Giampiero; Quagliolo, Michela; Centenaro, Giuseppe Riccardo; Purrello, Francesco; Di Pino, Antonino; Piro, Salvatore; Mancuso, Gerardo; Calipari, Daniela; Bartone, Mosè; Gullo, Francesco; Cortellaro, Michele; Magenta, Marina; Perego, Francesca; Meroni, Maria Rachele; Cicardi, Marco; Magenta, Antonio Gidaro Marina; Sacco, Andrea; Bonelli, Antonio; Dentamaro, Gaetano; Rozzini, Renzo; Falanga, Lina; Giordano, Ale
abstract
Background and purpose Women live longer and outnumber men. On the other hand, older women develop more chronic diseases and conditions such as arthritis, osteoporosis and depression, leading to a greater number of years of living with disabilities. The aim of this study was to describe whether or not there are gender differences in the demographic profile, disease distribution and outcome in a population of hospitalized elderly people. Methods Retrospective observational study including all patients recruited for the REPOSI study in the year 2010. Analyses are referred to the whole group and gender categorization was applied. Results A total of 1380 hospitalized elderly subjects, 50.5% women and 49.5% men, were considered. Women were older than men, more often widow and living alone or in nursing homes. Disease distribution showed that malignancy, diabetes, coronary artery disease, chronic kidney disease and chronic obstructive pulmonary disease were more frequent in men, but hypertension, osteoarthritis, anemia and depression were more frequent in women. Severity and comorbidity indexes according to the Cumulative Illness Rating Scale (CIRS-s and CIRS-c) were higher in men, while cognitive impairment evaluated by the Short Blessed Test (SBT), mood disorders by the Geriatric Depression Scale (GDS) and disability in daily life measured by Barthel Index (BI) were worse in women. In-hospital and 3-month mortality rates were higher in men. Conclusions Our study showed a gender dimorphism in the demographic and morbidity profiles of hospitalized elderly people, emphasizing once more the need for a personalized process of healthcare.
2014
- Gout, allopurinol intake and clinical outcomes in the hospitalized multimorbid elderly
[Articolo su rivista]
Franchi, Carlotta; Salerno, Francesco; Conca, Alessio; Djade, Codjo D; Tettamanti, Mauro; Pasina, Luca; Corrao, Salvatore; Marengoni, Alessandra; Marcucci, Maura; Mannucci, Pier Mannuccio; Nobili, Alessandro; REPOSI Study, Group; Bertolotti, Marco; Becchi, Maria Angela
abstract
Increased serum uric acid has been considered a cardiovascular risk factor but no study has assessed its relation with hospital mortality or length of stay. On the basis of data obtained from a prospective registry, the prevalence of gout/hyperuricemia and its association with these and other clinical parameters was evaluated in an Italian cohort of elderly patients acutely admitted to internal medicine or geriatric wards.
2014
- Heart failure and chronic kidney disease in a registry of internal medicine wards
[Articolo su rivista]
Mannucci, P. M.; Nobili, A.; Tettamanti, M.; Pasina, L.; Franchi, C.; Salerno, F.; Corrao, S.; Marengoni, A.; Iorio, A.; Marcucci, M.; Sparacio, E.; Alborghetti, S.; Di Costanzo, R.; Djade, C. D.; Prisco, D.; Silvestri, E.; Cenci, C.; Barnini, T.; Delitala, G.; Carta, S.; Atzori, S.; Guarnieri, G.; Zanetti, M.; Spalluti, A.; Serra, M. G.; Bleve, M. A.; Vanoli, M.; Grignani, G.; Casella, G.; Gasbarrone, L.; Maniscalco, G.; Gunelli, M.; Tirotta, D.; Brucato, A.; Ghidoni, S.; Di Corato, P.; Bernardi, M.; Li Bassi, S.; Santi, L.; Agnelli, G.; Marchesini, E.; Mannarino, E.; Lupattelli, G.; Rondelli, P.; Paciullo, F.; Fabris, F.; Carlon, M.; Turatto, F.; Baroni, M. C.; Zardo, M.; Manfredini, R.; Molino, C.; Pala, M.; Fabbian, F.; Nuti, R.; Valenti, R.; Ruvio, M.; Cappelli, S.; Paolisso, G.; Rizzo, M. R.; Laieta, M. T.; Salvatore, T.; Sasso, F. C.; Utili, R.; Mangoni, E. D.; Pinto, D.; Olivieri, O.; Stanzial, A. M.; Fellin, R.; Volpato, S.; Fotini, S.; Barbagallo, M.; Dominguez, L.; Plances, L.; D'Angelo, D.; Rini, G.; Mansueto, P.; Pepe, I.; Licata, G.; Calvo, L.; Valenti, M.; Borghi, C.; Strocchi, E.; Rinaldi, E. R.; Zoli, M.; Fabbri, E.; Magalotti, D.; Auteri, A.; Pasqui, A. L.; Puccetti, L.; Pasini, F. L.; Capecchi, P. L.; Bicchi, M.; Sabba, C.; Vella, F. S.; Marseglia, A.; Luglio, C. V.; Palasciano, G.; Modeo, M. E.; Aquilino, A.; Raffaele, P.; Pugliese, S.; Capobianco, C.; Postiglione, A.; Barbella, M. R.; De Stefano, F.; Fenoglio, L.; Brignone, C.; Bracco, C.; Giraudo, A.; Musca, G.; Cuccurullo, O.; Cricco, L.; Fiorentini, A.; Cappellini, M. D.; Fabio, G.; Seghezzi, S.; De Amicis, M. M.; Fargion, S.; Bonara, P.; Bulgheroni, M.; Lombardi, R.; Magrini, F.; Massari, F.; Tonella, T.; Peyvandi, F.; Tedeschi, A.; Rossio, R.; Moreo, G.; Ferrari, B.; Roncari, L.; Monzani, V.; Savojardo, V.; Folli, C.; Magnini, M.; Mari, D.; Rossi, P. D.; Damanti, S.; Prolo, S.; Lilleri, M. S.; Micale, G.; Podda, M.; Selmi, C.; Meda, F.; Accordino, S.; Conca, A.; Monti, V.; Corazza, G. R.; Miceli, E.; Lenti, M. V.; Padula, D.; Balduini, C. L.; Bertolino, G.; Provini, S.; Quaglia, F.; Murialdo, G.; Bovio, M.; Dallegri, F.; Ottonello, L.; Quercioli, A.; Barreca, A.; Secchi, M. B.; Ghelfi, D.; Chin, W. S.; Carassale, L.; Caporotundo, S.; Anastasio, L.; Sofia, L.; Carbone, M.; Traisci, G.; De Feudis, L.; Di Carlo, S.; Davi, G.; Guagnano, M. T.; Sestili, S.; Bergami, E.; Rizzioli, E.; Cagnoni, C.; Bertone, L.; Manucra, A.; Buratti, A.; Tognin, T.; Liberato, N. L.; Bernasconi, G.; Nardo, B.; Bianchi, G. B.; Ospedale, S. G.; Benetti, G.; Quagliolo, M.; Centenaro, G. R.; Purrello, F.; Di Pino, A.; Piro, S.; Mancuso, G.; Calipari, D.; Bartone, M.; Gullo, F.; Cortellaro, M.; Magenta, M.; Perego, F.; Meroni, M. R.; Cicardi, M.; Magenta, A. G. M.; Sacco, A.; Bonelli, A.; Dentamaro, G.; Rozzini, R.; Falanga, L.; Giordano, A.; Perin, P. C.; Lorenzati, B.; Gruden, G.; Bruno, G.; Montrucchio, G.; Greco, E.; Tizzani, P.; Fera, G.; Di Luca, M. L.; Renna, D.; Perciccante, A.; Coralli, A.; Tassara, R.; Melis, D.; Rebella, L.; Menardo, G.; Bottone, S.; Sferrazzo, E.; Ferri, C.; Striuli, R.; Scipioni, R.; Salmi, R.; Gaudenzi, P.; Gamberini, S.; Ricci, F.; Morabito, C.; Fava, R.; Semplicini, A.; Gottardo, L.; Vendemiale, G.; Serviddio, G.; Forlano, R.; Bolondi, L.; Rasciti, L.; Serio, I.; Masala, C.; Mammarella, A.; Raparelli, V.; Fanelli, F. R.; Delfino, M.; Amoroso, A.; Violi, F.; Basili, S.; Perri, L.; Serra, P.; Fontana, V.; Falcone, M.; Landolfi, R.; Grieco, A.; Gallo, A.; Zuccala, G.; Franceschi, F.; De Marco, G.; Chiara, C.; Marta, S.; Bellusci, M.; Setti, D.; Pedrazzoli, F.; Romanelli, G.; Pirali, C.; Amolini, C.; Rosei, E. A.; Rizzoni, D.; Castoldi, L.; Picardi, A.; Gentilucci, U. V.; Mazzarelli, C.; Gallo, P.; Guasti, L.; Castiglioni, L.; Maresca, A.; Squizzato, A.; Contini, S.; Molaro, M.; Annoni, G.; Corsi, M.; Zazzetta, S.; Bertolotti, M.; Mussi, C.; Scotto, R.; Ferri, M. A.; Veltri, F.; Arturi, F.; Succurro, E.; Sesti, G.; Gualtieri, U.; Perticone, F.; Sciacqua
abstract
Background: The aim of the present study was to evaluate the association between heart failure (HF) and chronic kidney disease (CKD) in tertiary care centers using the clinical records of patients enrolled in internal medicine departments.Patients and methods: We used the clinical records of 1380 elderly patients to identify patients with a history of HF and CKD using admission ICD codes and glomerular filtration rate (GFR) formulas. Magnitude and strength of such associations were investigated by univariable and multivariable analysis.Results: Of the 1380 patients enrolled, 27.9% had HF (age 80 ± 7, BMI 27 ± 6 kg/m2) and 17.4% CKD (age 81 ± 7, BMI 26.8 ± 6 kg/m2). Both groups were significantly older (P <' 0.0001) with BMI higher than the patients without those diagnosis (P < 0.02). Patients with a history of CKD showed higher non-fasting glycaemia (140 ± 86 vs. 125 ± 63 mg/dL, P < 0.001). CKD was significantly associated with HF (P < 0.0001). Patients with HF had an estimated GFR lower than patients without HF (P < 0.0001). Comorbidity and severity indices were significantly higher in subjects with HF (P < 0.0001) and CKD (P < 0.0001) than in those without. Multivariable analysis showed a significant association between HF and age (for five years increase OR 1.13, P < 0.009), BMI (for each 3 kg/m2 increase OR 1.15, P < 0.001), GFR (for each decrease of 10 mL/min increase OR 0.92, P < 0.002) and severity index (IS) (for each 0.25 units increase OR 1.43, P < 0.001).Conclusion: HF on admission is strongly associated with CKD, older age, BMI, and SI. These data focus the value of epidemiological studies such REPOSI in identifying and monitoring multimorbidity in elderly.
2014
- In Vivo Degradation of Cholesterol to Bile Acids Is Reduced in Patients Receiving Parenteral Nutrition.
[Articolo su rivista]
Carulli, Lucia; Del Puppo, M; Anzivino, Claudia; Zambianchi, L; Gabbi, C; Baldelli, Enrica; Odoardi, Mr; Loria, Paola; Carulli, Nicola; Bertolotti, Marco
abstract
Background. Artificial nutrition is frequently associated with hepatobiliary complications, probably due to the inherent derangement of the gastrointestinal tract physiology. Alterations of hepatic lipid metabolism are likely to be involved. The aim of the present study was to investigate the effect of artificial nutrition on bile acid production, a key event in cholesterol homeostasis, in humans. Patients and Methods. Eleven patients receiving artificial nutrition, either parenteral nutrition (PN; n = 6) or enteral nutrition (EN; n = 5) with no previous history of liver disease, underwent analysis of cholesterol 7α-hydroxylation rates in vivo, a measure of bile acid formation, by isotope release analysis after intravenous injection of [7α-(3)H]cholesterol. The results were compared with those obtained in a population of 16 age-matched control subjects. Results. Hydroxylation rates were lower in patients with artificial nutrition (PN: 94 ± 13 mg/d; EN: 230 ± 39 mg/d, mean ± SEM) when compared with controls (385 ± 47 mg/d) (P < .01, 1-way analysis of variance). In a patient receiving EN, hydroxylation rates increased 3.5-fold after treatment with the cholecystokinin analogue ceruletide (20 µg bid for 2 weeks intramuscularly). Serum lathosterol-to-cholesterol ratio, a marker of cholesterol synthesis, was also significantly reduced in artificial nutrition, whereas serum levels of fibroblast growth factor 19 (FGF19) were increased. Conclusion. In vivo 7α-hydroxylation is suppressed in artificial nutrition, particularly in PN. The finding associates with reduced cholesterol production, possibly as a metabolic consequence. The data suggest a regulatory role of gastrointestinal hormones and FGF19 on bile acid production and might suggest a pathophysiological basis for some common complications of artificial nutrition, such as gallstone disease and cholestasis.
2014
- Lung fibrosis, bone marrow fibrosis and liver cirrhosis: A Short Telomere Syndrome or a casual association?
[Articolo su rivista]
Carulli, Lucia; Anzivino, Claudia; Bertolotti, Marco; Loria, Paola; Richeldi, Luca; Cerri, Stefania
abstract
Background: Telomere-mediated disease has diverse presentations that span the age spectrum. Their type, age of onset,
and severity depend on the extent of the telomere length defect. During adult life, telomerase mutations may represent risk
factors rather than genetic determinants and need other factors to contribute to disease development. This is case of
diseases such as aplastic anemia, pulmonary fibrosis and liver cirrhosis which may occur as single disease or together in a
syndromic clustering. Here we report a case of a man most likely affected by a short telomere syndrome.
Case report: A 58 years old man, presented for evaluation of pulmonary fibrosis diagnosed few years earlier in a different
medical center. He also presented a mild bone marrow fibrosis and a liver cirrhosis, both diagnosed one year prior
evaluation with a bone marrow analysis and liver biopsy. The patient was an active smoker, obese, with digital clubbing
and inspiratory Velcro crackles at the right lower lobe. Laboratory tests showed thrombocytopenia and liver enzymes
alteration. He rapidly developed ascites and progression of the pulmonary fibrosis, the patient became oxygen-dependent
in few months.
Methods: Sequencing and mutation analysis of hTERT and hTERC genes, Leukocyte Telomere length (LTL) and
Telomerase activity (TA) were evaluated.
Results: In our patient LTL was shorter and TA reduced compared to the controls. Genes sequencing did not show any
hTERT and hTERC mutations.
Conclusions: This is a report on a short telomere syndrome involving lung, liver and bone marrow, associated to very
short telomere and absent telomerase activity not in the setting of dyskeratosis congenita.
The fact that short telomeres mediate inflammation and fibrosis provides a rationale for pursuing translational strategies
aimed at preventing telomere shortening or its cellular consequences as a therapeutic approach
2014
- Multimorbidity and polypharmacy in the elderly: Lessons from REPOSI
[Articolo su rivista]
Mannucci, Pier Mannuccio; Nobili, Alessandro; Mannucci, Pier Mannuccio; Nobili, Alessandro; Tettamanti, Mauro; Pasina, Luca; Franchi, Carlotta; Sparacio, Eleonora; Alborghetti, Stefania; Di Costanzo, Rosa; Eldin, Tarek Kamal; Tettamanti, Mauro; Djade, Codjo Djignefa; Salerno, Francesco; Corrao, Salvatore; Marengoni, Alessandra; Marcucci, Maura; Prisco, Domenico; Silvestri, Elena; Cenci, Caterina; Barnini, Tommaso; Delitala, Giuseppe; Carta, Stefano; Atzori, Sebastiana; Guarnieri, Gianfranco; Zanetti, Michela; Spalluti, Annalisa; Serra, Maria Grazia; Bleve, Maria Antonietta; Vanoli, Massimo; Grignani, Giulia; Casella, Gianluca; Gasbarrone, Laura; Maniscalco, Giorgio; Gunelli, Massimo; Tirotta, Daniela; Brucato, Antonio; Ghidoni, Silvia; Di Corato, Paola; Bernardi, Mauro; Bassi, Silvia Li; Santi, Luca; Agnelli, Giancarlo; Iorio, Alfonso; Marchesini, Emanuela; Mannarino, Elmo; Lupattelli, Graziana; Rondelli, Pamela; Paciullo, Francesco; Fabris, Fabrizio; Carlon, Michela; Turatto, Francesca; Baroni, Maria Cristina; Zardo, Marianna; Manfredini, Roberto; Molino, Christian; Pala, Marco; Fabbian, Fabio; Nuti, Ranuccio; Valenti, Roberto; Ruvio, Martina; Cappelli, Silvia; Paolisso, Giuseppe; Rizzo, Maria Rosaria; Laieta, Maria Teresa; Salvatore, Teresa; Sasso, Ferdinando Carlo; Utili, Riccardo; Mangoni, Emanuele Durante; Pinto, Daniela; Olivieri, Oliviero; Stanzial, Anna Maria; Fellin, Renato; Volpato, Stefano; Fotini, Sioulis; Barbagallo, Mario; Dominguez, Ligia; Plances, Lidia; D’Angelo, Daniela; Rini, Giovanbattista; Mansueto, Pasquale; Pepe, Ilenia; Licata, Giuseppe; Calvo, Luigi; Valenti, Maria; Borghi, Claudio; Strocchi, Enrico; Rinaldi, Elisa Rebecca; Zoli, Marco; Fabbri, Elisa; Magalotti, Donatella; Auteri, Alberto; Pasqui, Anna Laura; Puccetti, Luca; Pasini, Franco Laghi; Capecchi, Pier Leopoldo; Bicchi, Maurizio; Sabbà, Carlo; Vella, Francesco Saverio; Marseglia, Alessandro; Luglio, Chiara Valentina; Palasciano, Giuseppe; Modeo, Maria Ester; Aquilino, Annamaria; Raffaele, Pallante; Pugliese, Stefania; Capobianco, Caterina; Postiglione, Alfredo; Barbella, Maria Rosaria; De Stefano, Francesco; Fenoglio, Luigi; Brignone, Chiara; Bracco, Christian; Giraudo, Alessia; Musca, Giuseppe; Cuccurullo, Olga; Cricco, Luigi; Fiorentini, Alessandra; Cappellini, Maria Domenica; Fabio, Giovanna; Seghezzi, Sonia; De Amicis, Margherita Migone; Fargion, Silvia; Bonara, Paola; Bulgheroni, Mara; Lombardi, Rosa; Magrini, Fabio; Massari, Ferdinando; Tonella, Tatiana; Peyvandi, Flora; Tedeschi, Alberto; Rossio, Raffaella; Moreo, Guido; Ferrari, Barbara; Roncari, Luisa; Monzani, Valter; Savojardo, Valeria; Folli, Christian; Magnini, Maria; Mari, Daniela; Rossi, Paolo Dionigi; Damanti, Sarah; Prolo, Silvia; Lilleri, Maria Sole; Cricco, Luigi; Fiorentini, Alessandra; Micale, Giuliana; Podda, Mauro; Selmi, Carlo; Meda, Francesca; Salerno, Francesco; Accordino, Silvia; Conca, Alessio; Monti, Valentina; Corazza, Gino Roberto; Miceli, Emanuela; Lenti, Marco Vincenzo; Padula, Donatella; Balduini, Carlo L.; Bertolino, Giampiera; Provini, Stella; Quaglia, Federica; Murialdo, Giovanni; Bovio, Marta; Dallegri, Franco; Ottonello, Luciano; Quercioli, Alessandra; Barreca, Alessandra; Secchi, Maria Beatrice; Ghelfi, Davide; Chin, Wu Sheng; Carassale, Laura; Caporotundo, Silvia; Anastasio, Luigi; Sofia, Lucia; Carbone, Maria; Traisci, Giancarlo; De Feudis, Lucrezia; Di Carlo, Silvia; Davì, Giovanni; Guagnano, Maria Teresa; Sestili, Simona; Bergami, Elisabetta; Rizzioli, Emanuela; Cagnoni, Carlo; Bertone, Luca; Manucra, Antonio; Buratti, Alberto; Tognin, Tiziana; Liberato, Nicola Lucio; Bernasconi, Giordano; Nardo, Barbara; Bianchi, Giovanni Battista; Ospedale, Sabrina Giaquinto; Benetti, Giampiero; Quagliolo, Michela; Centenaro, Giuseppe Riccardo; Purrello, Francesco; Di Pino, Antonino; Piro, Salvatore; Mancuso, Gerardo; Calipari, Daniela; Bartone, Mosè; Gullo, Francesco; Cortellaro, Michele; Magenta, Marina; Perego, ;
abstract
The dramatic demographic changes that are occurring in the third millennium are modifying the mission of generalist professionals such as primary care physicians and internists. Multiple chronic diseases and the related prescription of multiple medications are becoming typical problems and present many challenges. Unfortunately, the available evidence regarding the efficacy of medications has been generated by clinical trials involving patients completely different from those currently admitted to internal medicine: much younger, affected by a single disease and managed in a highly controlled research environment. Because only registries can provide information on drug effectiveness in real-life conditions, REPOSI started in 2008 with the goal of acquiring data on elderly people acutely admitted to medical or geriatric hospital wards in Italy. The main goals of the registry were to evaluate drug prescription appropriateness, the relationship between multimorbidity/polypharmacy and such cogent outcomes as hospital mortality and re-hospitalization, and the identification of disease clusters that most often concomitantly occur in the elderly. The findings of 3-yearly REPOSI runs (2008, 2010, 2012) suggest the following pertinent tasks for the internist in order to optimally handle their elderly patients: the management of multiple medications, the need to become acquainted with geriatric multidimensional tools, the promotion and implementation of a multidisciplinary team approach to patient health and care and the corresponding involvement of patients and their relatives and caregivers. There is also a need for more research, tailored to the peculiar features of the multimorbid elderly patient.
2014
- Nonalcoholic fatty liver disease and aging: epidemiology to management
[Articolo su rivista]
Bertolotti, Marco; Lonardo, Amedeo; Mussi, Chiara; Baldelli, Enrica; Pellegrini, Elisa; Ballestri, Stefano; Romagnoli, Dante; Loria, Paola
abstract
Nonalcoholic fatty liver disease (NAFLD) is common in the elderly, in whom it carries a more substantial burden of hepatic (nonalcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma) and extra-hepatic manifestations and complications (cardiovascular disease, extrahepatic neoplasms) than in younger age groups. Therefore, proper identification and management of this condition is a major task for clinical geriatricians and geriatric hepatologists. In this paper, the epidemiology and pathophysiology of this condition are reviewed, and a full discussion of the link between NAFLD and the aspects that are peculiar to elderly individuals is provided; these aspects include frailty, multimorbidity, polypharmacy and dementia. The proper treatment strategy will have to consider the peculiarities of geriatric patients, so a multidisciplinary approach is mandatory. Non-pharmacological treatment (diet and physical exercise) has to be tailored individually considering the physical limitations of most elderly people and the need for an adequate caloric supply. Similarly, the choice of drug treatment must carefully balance the benefits and risks in terms of adverse events and pharmacological interactions in the common context of both multiple health conditions and polypharmacy. In conclusion, further epidemiological and pathophysiological insight is warranted. More accurate understanding of the molecular mechanisms of geriatric NAFLD will help in identifying the most appropriate diagnostic and therapeutic approach for individual elderly patients.
2014
- Risk of birth defects associated with maternal pregestational diabetes.
[Articolo su rivista]
Vinceti, Marco; Malagoli, Carlotta; Rothman, Kj; Rodolfi, R; Astolfi, G; Calzolari, E; Puccini, A; Bertolotti, Marco; Lunt, M; Paterlini, L; Martini, M; Nicolini, F.
abstract
Maternal diabetes preceding pregnancy may increase the risk of birth defects in the offspring, but not all studies confirm this association, which has shown considerable variation over time, and the effect of having type 1 versus type 2 diabetes is unclear. We conducted a population-based cohort study in the Northern Italy Emilia-Romagna region linking administrative databases with a Birth Defects Registry. From hospital discharge records we identified all diabetic pregnancies during 1997-2010, and a population of non-diabetic parturients matched for age, residence, year and delivery hospital. We collected available information on education, smoking and drug prescriptions, from which we inferred the type of diabetes. We found 62 malformed infants out of 2,269 births among diabetic women, and 162 out of 10,648 births among non-diabetic women. The age-standardized prevalence ratio (PR) of malformation associated with maternal pregestational diabetes was 1.79 (95 % confidence interval 1.34-2.39), a value that varied little by age. Type of diabetes strongly influenced the PR, with higher values related to type 2 diabetic women. Most major subgroups of anomalies had PRs above 1, including cardiovascular, genitourinary, musculoskeletal, and chromosomal abnormalities. There was an unusually high PR for the rare defect 'extra-ribs', but it was based on only two cases. This study indicates that maternal pregestational type 2 diabetes is associated with a higher prevalence of specific birth defects in offspring, whereas for type 1 diabetic mothers, particularly in recent years, the association was unremarkable.
2013
- ABCB4 and ABCB11 mutations in intrahepatic cholestasis of pregnancy in an Italian population
[Articolo su rivista]
Anzivino, Claudia; Odoardi, Maria Rosaria; Meschiari, Erica; Baldelli, Enrica; Facchinetti, Fabio; Neri, Isabella; Ruggiero, Giuseppe; Zampino, Rosa; Bertolotti, Marco; Loria, Paola; Carulli, Lucia
abstract
Background: Genetic alterations in the ATP-binding cassette subfamily B member 4 (ABCB4) and ATPbinding cassette subfamily B member 11 (ABCB11) have been associated to the onset of intrahepatic cholestasis of pregnancy (ICP) in predisposed women.
Aims: To identify new and/or frequent ABCB4 and ABCB11 genes variants in a cohort of Italian patients with ICP and to evaluate the possible pathogenetic role for the novel mutations identified.
Methods: DNA of 33 unrelated Italian women with obstetric cholestasis were screened for mutations in the entire coding sequence of ABCB4 and ABCB11 genes. Polymerase chain reaction and automated sequencing was performed on the 27 coding exons of both genes.
Results: Genotyping revealed 11 mutations, 5 of whom were novel variants: 2 localized on ABCB4 (p.I587DfsX603, p.I738LfsX744) and 3 on ABCB11 (p.V284D, p.Q558H, p.P731S). The most severe phenotypes were associated with the variants p.I587DfsX603, p.I738LfsX744 and p.V284D. Moreover, the already described mutation p.N510S found in ABCB4 seems to be strictly involved in the onset of ICP in that particular patient.
Conclusions: Our data support the hypothesis of a significant involvement of ABCB4 mutations in the onset of ICP, but also confirm an important role for ABCB11 mutations in increasing the susceptibility to cholestasis of pregnancy.
2013
- Hypertensive disease in the elderly: Predictors of clinical evolution in a follow-up study
[Abstract in Rivista]
Mussi, C.; Venturelli, F.; Finelli, M. E.; Neviani, F.; Martini, E.; Scotto, R.; Vedele, C.; Patti, C.; Lancellotti, G.; Bertolotti, M.; Neri, M.
abstract
Aims.– Hypertension is the first etiological factor of cerebrovascular disease in the elderly. Aims of the study: – to assess at the follow-up the rates of mortality, morbidity, disability, cognitive deficits; – to identify the major predictors of clinical outcomes.
Materials and methods.– Sixty-six patients were recruited in a follow-up study of 2.5 years, (inclusion criteria: age > 60 years, hypertension; MMSE > 15/30; exclusion criteria: high comorbidity index, diabetes, psychiatric disease, severe sensorial impairments), and they were matched with a sample of InChianty Longitudinal Study.
Results.– Mortality: no significant differences between expected and observed data (vascularity index (VI) in neuroimaging: main predictor of mortality). Comorbidities: significant reduction of the classes with lower comorbidity, paralleled by an increase of the higher levels of comorbidity. Disability: same trend of comorbidity, namely the significant shifting toward the lowest of the three levels of competence considered; an high VI was a predictor of functional decline as well as the level of cognitive impairment, of arterial stiffness and BMI. Cognitive performance: trend to decline of the overall performance, in both the “bedside” MMSE and the most complex CAMCOG; only long-term memory showed a statistically significant impairment. VI, ApoE and hypercholesterolemia, were the strongest predictors of worsening of cognitive performance. Conclusions.– Hypertensive disease in the elderly could be the source of a significant worsening of the considered outcomes. It is remarkable the reduction of competence in daily activities, explained by the convergence of the condition of frailty and difficulties of adequate response of the health-care system.
2013
- Is nonalcoholic steatohepatitis associated with a high-though-normal thyroid stimulating hormone level and lower cholesterol levels?
[Articolo su rivista]
Carulli, Lucia; Ballestri, Stefano; Lonardo, Amedeo; Lami, Francesca; Violi, Enrico; Losi, Luisa; Bonilauri, Lisa; Verrone, Anna Maria; Odoardi, Maria Rosaria; Scaglioni, Federica; Bertolotti, Marco; Loria, Paola
abstract
Hypothyroidism is associated with the risk of development of the metabolic syndrome (MS) and hypercholesterolemia. Direct evidence that hypothyroidism might be associated with advanced chronic liver disease via nonalcoholic steatohepatitis (NASH) is limited. We studied the relationship between thyroid hormones, thyroid stimulating hormone (TSH), cholesterol, and NASH. In consecutive euthyroid patients with biopsy-proven nonalcoholic fatty liver disease, TSH and thyroid hormone (FT3 and FT4) concentrations were compared in 25 patients with steatosis and 44 non-cirrhotic NASH patients featuring concurrent ballooning, lobular inflammation and steatosis. The MS was diagnosed according to ATP III criteria. A meta-analysis of previously published studies was performed to evaluate whether NASH, compared to simple steatosis, is associated with lower cholesterol levels. At univariate analysis, compared to those with steatosis, patients with NASH have a wider waist, elevated levels of BMI, ALT, AST, fasting insulin, HOMA-IR, ferritin, TSH and a lower serum cholesterol. At stepwise multivariable logistic regression analysis, the independent predictors of NASH are high HOMA and TSH and lower total cholesterol (Model 1); MS and high TSH (Model 2). At meta-analysis, serum total cholesterol levels are significantly lower in predominantly non-cirrhotic NASH than in simple steatosis. This study provides cross-sectional and meta-analytic evidence that, in euthyroid patients, high-though-normal TSH values are independently associated with NASH. Further work is needed to ascertain the role, if any, of lower cholesterol serum levels in assisting in the diagnosis of NASH.
2013
- Lipoprotein glomerulopathy associated with a mutation in apolipoprotein e
[Articolo su rivista]
Magistroni, Riccardo; Bertolotti, Marco; Furci, Luciana; Fano, Rita Adriana; Leonelli, Marco; Pisciotta, Livia; Pellegrini, Elisa; Calabresi, Laura; Bertolini, Stefano; Calandra, Sebastiano
abstract
Lipoprotein glomerulopathy is a pathological condition characterized by lipid accumulation in the glomerular capillaries that has been associated with the presence of rare mutants of apolipoprotein E (ApoE). We describe a 51-year-old Italian patient presenting Type III hyperlipidemia and proteinuria in whom renal biopsy showed capillary ectasia and intraluminal lipid deposits, suggesting the diagnosis of lipoprotein glomerulopathy. The patient, who had elevated plasma ApoE level, was found to be heterozygous for a mutation in ApoE (Arg150Cys), designated apoEMODENA. This mutation induces the formation of ApoE dimers that are detectable under non-reducing conditions. Treatment with hypolipidemic drugs did not result in a complete remission of the proteinuria and was accompanied by a slow but progressive worsening of renal function with the persistence of intracapillary lipid thrombi. The introduction of low-density lipoprotein aphaeresis combined with a more aggressive lipid lowering and antihypertensive therapy resulted in the remission of proteinuria and a substantial improvement of renal function. Switching from low-density lipoprotein aphaeresis to plasma filtration did not result in an equivalent control of renal damage. The patient died of intracranial hemorrhage during an acute episode of malignant hypertension.
2013
- Prevalence of peripheral artery disease by abnormal ankle-brachial index in atrial fibrillation: implications for risk and therapy
[Articolo su rivista]
Violi, Francesco; Daví, Giovanni; Hiatt, William; Lip, Gregory Y. H; Corazza, Gino R; Perticone, Francesco; Proietti, Marco; Pignatelli, Pasquale; Vestri, Anna R; Basili, Stefania; ARAPACIS Study, Investigators; Bertolotti, Marco
abstract
Nonvalvular atrial fibrillation (NVAF) is the most
common sustained arrhythmia encountered in clinical practice and
is associated with a 5-fold increased risk for stroke
2013
- Prophylaxis of venous thromboembolism in elderly patients with multimorbidity
[Articolo su rivista]
Marcucci, Maura; Iorio, Alfonso; Nobili, Alessandro; Tettamanti, Mauro; Pasina, Luca; Djade, Codjo Djignefa; Marengoni, Alessandra; Salerno, Francesco; Corrao, Salvatore; Mannucci, Pier Mannuccio; Franchi, Carlotta; Sparacio, Eleonora; Alborghetti, Stefania; Di Costanzo, Rosa; Prisco, Domenico; Silvestri, Elena; Cenci, Caterina; Barnini, Tommaso; Delitala, Giuseppe; Carta, Stefano; Atzori, Sebastiana; Guarnieri, Gianfranco; Zanetti, Michela; Spalluti, Annalisa; Serra, Maria Grazia; Bleve, Maria Antonietta; Vanoli, Massimo; Grignani, Giulia; Casella, Gianluca; Gasbarrone, Laura; Maniscalco, Giorgio; Gunelli, Massimo; Tirotta, Daniela; Brucato, Antonio; Ghidoni, Silvia; Di Corato, Paola; Bernardi, Mauro; Bassi, Silvia Li; Santi, Luca; Agnelli, Giancarlo; Marchesini, Emanuela; Mannarino, Elmo; Lupattelli, Graziana; Rondelli, Pamela; Paciullo, Francesco; Fabris, Fabrizio; Carlon, Michela; Turatto, Francesca; Baroni, Maria Cristina; Zardo, Marianna; Manfredini, Roberto; Molino, Christian; Pala, Marco; Fabbian, Fabio; Nuti, Ranuccio; Valenti, Roberto; Ruvio, Martina; Cappelli, Silvia; Paolisso, Giuseppe; Rizzo, Maria Rosaria; Laieta, Maria Teresa; Salvatore, Teresa; Sasso, Ferdinando Carlo; Utili, Riccardo; Mangoni, Emanuele Durante; Pinto, Daniela; Olivieri, Oliviero; Stanzial, Anna Maria; Fellin, Renato; Volpato, Stefano; Fotini, Sioulis; Barbagallo, Mario; Dominguez, Ligia; Plances, Lidia; D’Angelo, Daniela; Rini, Giovanbattista; Mansueto, Pasquale; Pepe, Ilenia; Licata, Giuseppe; Calvo, Luigi; Valenti, Maria; Borghi, Claudio; Strocchi, Enrico; Rinaldi, Elisa Rebecca; Zoli, Marco; Fabbri, Elisa; Magalotti, Donatella; Auteri, Alberto; Pasqui, Anna Laura; Puccetti, Luca; Pasini, Franco Laghi; Capecchi, Pier Leopoldo; Bicchi, Maurizio; Sabbà, Carlo; Vella, Francesco Saverio; Marseglia, Alessandro; Luglio, Chiara Valentina; Palasciano, Giuseppe; Modeo, Maria Ester; Aquilino, Annamaria; Raffaele, Pallante; Pugliese, Stefania; Capobianco, Caterina; Postiglione, Alfredo; Barbella, Maria Rosaria; De Stefano, Francesco; Fenoglio, Luigi; Brignone, Chiara; Bracco, Christian; Giraudo, Alessia; Musca, Giuseppe; Cuccurullo, Olga; Cricco, Luigi; Fiorentini, Alessandra; Cappellini, Maria Domenica; Fabio, Giovanna; Seghezzi, Sonia; De Amicis, Margherita Migone; Fargion, Silvia; Bonara, Paola; Bulgheroni, Mara; Lombardi, Rosa; Magrini, Fabio; Massari, Ferdinando; Tonella, Tatiana; Peyvandi, Flora; Tedeschi, Alberto; Rossio, Raffaella; Moreo, Guido; Ferrari, Barbara; Roncari, Luisa; Monzani, Valter; Savojardo, Valeria; Folli, Christian; Magnini, Maria; Mari, Daniela; Rossi, Paolo Dionigi; Damanti, Sarah; Prolo, Silvia; Lilleri, Maria Sole; Micale, Giuliana; Podda, Mauro; Selmi, Carlo; Meda, Francesca; Accordino, Silvia; Conca, Alessio; Monti, Valentina; Corazza, Gino Roberto; Miceli, Emanuela; Lenti, Marco Vincenzo; Padula, Donatella; Balduini, Carlo L.; Bertolino, Giampiera; Provini, Stella; Quaglia, Federica; Murialdo, Giovanni; Bovio, Marta; Dallegri, Franco; Ottonello, Luciano; Quercioli, Alessandra; Barreca, Alessandra; Secchi, Maria Beatrice; Ghelfi, Davide; Chin, Wu Sheng; Carassale, Laura; Caporotundo, Silvia; Anastasio, Luigi; Sofia, Lucia; Carbone, Maria; Traisci, Giancarlo; De Feudis, Lucrezia; Di Carlo, Silvia; Daví, Giovanni; Guagnano, Maria Teresa; Sestili, Simona; Bergami, Elisabetta; Rizzioli, Emanuela; Cagnoni, Carlo; Bertone, Luca; Manucra, Antonio; Buratti, Alberto; Tognin, Tiziana; Liberato, Nicola Lucio; Bernasconi, Giordano; Nardo, Barbara; Bianchi, Giovanni Battista; Benetti, Giampiero; Quagliolo, Michela; Centenaro, Giuseppe Riccardo; Purrello, Francesco; Di Pino, Antonino; Piro, Salvatore; Mancuso, Gerardo; Calipari, Daniela; Bartone, Mosè; Gullo, Francesco; Cortellaro, Michele; Magenta, Marina; Perego, Francesca; Meroni, Maria Rachele; Cicardi, Marco; Magenta, Antonio Gidaro Marina; Sacco, Andrea; Bonelli, Antonio; Dentamaro, Gaetano; Rozzini, Renzo; Falanga, Lina; Giordano
abstract
Pharmacological thromboprophylaxis (TP) is known to reduce venous thromboembolism (VTE) in medical inpatients, but the criteria for risk-driven prescription, safety and impact on mortality are still debated. We analyze data on elderly patients with multimorbidities admitted in the year 2010 to the Italian internal medicine wards participating in the REPOSI registry to investigate the rate of TP during the hospital stay, and analyze the factors that are related to its prescription. Multivariate logistic regression, area under the ROC curve and CART analysis were performed to look for independent predictors of TP prescription. Association between TP and VTE, bleeding and death in hospital and during the 3-month postdischarge follow-up were explored by logistic regression and propensity score analysis. Among the 1,380 patients enrolled, 171 (15.2%) were on TP during the hospital stay (162 on low molecular weight heparins, 9 on fondaparinux). The disability Barthel index was the main independent predictor of TP prescription. Rate of fatal and non-fatal VTE and bleeding during and after hospitalization did not differ between TP and non-TP patients. In-hospital and post-discharge mortality was significantly higher in patients on TP, that however was not an independent predictor of mortality. Among elderly medical patients there was a relatively low rate of TP, that was more frequently prescribed to patients with a higher degree of disability and who had an overall higher mortality.
2013
- Risk of birth defects associated with maternal pregestational diabetes: a population-based cohort study in northern Italy
[Abstract in Rivista]
Vinceti, Marco; Malagoli, Carlotta; Rodolfi, R; Rothman, K; Puccini, A; Lunt, M; Bertolotti, Marco; Astolfi, G; Calzolari, E; Nicolini, F.
abstract
Maternal diabetes preceding pregnancy, whether type-1 or type-2, appears to increase the risk of birth defects in the offspring, though several aspects of this relation are still unknown or controversial.
We conducted a large population-based cohort study in the Northern Italy region of Emilia-Romagna using administrative databases and a Birth Defects Registry. From hospital discharge records we identified all diabetic pregnancies during 1997-2010, and a population of non-diabetic parturients matched for age, province of residence, year and hospital of delivery. We collected where available information on drug prescriptions, from which we inferred the type of diabetes.
We found 62 malformed infants out of 2,269 births among diabetic women, and 162 out of 10,648 births among non-diabetic women. The prevalence ratio (PR) of malformation associated with maternal pregestational diabetes was 1.73 (95% confidence interval 1.28-2.33). Period of birth and type of diabetes strongly influenced the PR, with higher values estimates in the earliest periods and in type-2 diabetic women compared with type-1 diabetic mothers. The latter group exhibited no excess risk in the most recent period, 2006-2010, possibly owing to improvements in metabolic control over time. Most subgroups of anomalies had PRs above 1, but relevant and statistically more precise excess risks were seen for cardiovascular, genitourinary, musculoskeletal, and chromosomal abnormalities.
The present study indicates that maternal diabetes increases the risk of specific birth defects in offspring, particularly for type-2 diabetes, whereas for type-1 diabetic mothers in the most recent years, this was not the case.
2012
- DIABETES AND CARDIOVASCULAR EVENTS: USEFULNESS AND LIMITS OF RISK FUNCTIONS
[Articolo su rivista]
Bertolotti, Marco; Elisa, Pellegrini; Mauro, Maurantonio; Silvia, Venturi; Ganazzi, Dorval; Carulli, Lucia; Mussi, Chiara; Anzivino, Claudia; Loria, Paola; Carulli, Nicola
abstract
Cardiovascular diseases represent a leading cause of death and disability worldwide. Risk functions and algorithms have been constructed to estimate cardiovascular risk as the weighed sum of different variables, considered as risk factors. Basically all utilized functions consider age, gender, cigarette smoking status, some estimate of systemic blood pressure and of plasma lipid profile, and diabetes. The functions derived from the Framingham study are the most commonly utilized worldwide, even if their applicability to some geographical areas has been heavily questioned. Furthermore, almost all functions, including Framingham’s, consider diabetes only as a dichotomous (yes / no) variable, despite its heavy impact on cardiovascular risk. On the other hand, the risk engine developed by the United Kingdom Prevention of Diabetes Study (UKPDS) takes into account some variables which characterize diabetes and its severity.Evidence from an outpatient population of diabetic subjects in northern Italy has underlined the extreme variability of risk stratification when utilizing different risk functions; whereas anglo-american functions overestimate cardiovascular risk, Italian charts and functions tend to underestimate risk, particularly in women. Estimation of cardiovascular risk is largely dependent on the function adopted, and on the baseline risk of each cohort. Functions should be designed which are geographically homogeneous for a selected population, and which take into account variables that are specific for diabetes. This should hopefully allow appropriate identification of high risk subjects, and ultimately help to optimize the allocation of health care resources.
2012
- Effects of bile duct ligation and cholic acid treatment on fatty liver in two rat models of non-alcoholic fatty liver disease
[Articolo su rivista]
Gabbi, Chiara; Bertolotti, Marco; Anzivino, Claudia; Macchioni, Daria; Del Puppo, Marina; Ricchi, Matteo; Carubbi, Francesca; Tagliafico, Enrico; Romagnoli, Dante; Odoardi, Maria Rosaria; Loria, Paola; Losi, Luisa; Carulli, Nicola
abstract
Non-alcoholic fatty liver disease, one of the most prevalent liver disorders in Western countries, is characterized by hepatic accumulation of triglycerides. Bile acids have long been known to affect triglyceride homeostasis through a not completely understood mechanism.
2012
- Increased appearance rate of 27-hydroxycholesterol in vivo in hypercholesterolemia: A possible compensatory mechanism.
[Articolo su rivista]
Bertolotti, Marco; Del Puppo, M; Corna, F; Anzivino, Claudia; Gabbi, Chiara; Baldelli, Enrica; Carulli, Lucia; Loria, Paola; Galli Kienle, M; Carulli, Nicola
abstract
BACKGROUND AND AIMS: The first step in the alternative pathway of bile acid biosynthesis is the 27-hydroxylation of cholesterol, which takes place both in liver and extrahepatic tissues. This pathway is believed to play a role in peripheral cholesterol degradation. Aim of this study was to investigate theimpact of hyperlipidemia on 27-hydroxycholesterol appearance rate, and to assess the effects induced by treatment with statins. METHODS AND RESULTS: Seven patients with familial hypercholesterolemia and eight patients with familial combined hyperlipidemia underwent determination of 27-hydroxylation rates in vivo by i.v. infusion of deuterated 27-hydroxycholesterol. Isotope enrichment was assayed by gas chromatography-mass spectrometry, allowing to calculate 27-hydroxycholesterol appearance rates. Six normocholesterolemic subjects wereregarded as controls. In some hypercholesterolemic patients the infusions were repeated during treatment with atorvastatin or rosuvastatin. Hydroxylation rates were higher in hypercholesterolemic patients (8.7 ± 2.5 mg/h; controls,3.4 ± 2.0 mg/h; combined hyperlipidemia, 4.4 ± 1.6 mg/h; mean ± SD, P < 0.01 vs both). After statin treatment, both plasma cholesterol levels and hydroxylation rates dropped by nearly 50%. No difference was detectable between the two statins. A linear correlation was shown between plasma cholesterol and 27-hydroxylation rates. CONCLUSION: Hypercholesterolemia associates withincreased 27-hydroxycholesterol appearance rates, which decrease during hypocholesterolemic treatment. The correlation with cholesterol levels supports the view that 27-hydroxylation may act as a compensatory mechanism in a conditionof larger plasma cholesterol pool. A regulatory role for hepatic and extrahepatic nuclear receptors seems reasonable. These data prompt novel pharmacological approaches for the management of hypercholesterolemia and the prevention of atherosclerosis.
2012
- Meal-induced blood pressure variation and cardiovascular mortality in ambulatory hypertensive elderly patients: preliminary results.
[Articolo su rivista]
Zanasi, A; Tincani, E; Evandri, V; Giovanardi, P; Bertolotti, Marco; Rioli, G.
abstract
OBJECTIVES: : This prospective cohort study was designed to investigate the prevalence and the prognostic value of postprandial hypotension (PPH) in ambulatory hypertensive elderly patients without overt heart diseases, an issue that has never been evaluated so far.
METHODS: : All patients consecutively referred to our cardiologic clinic in the period from January 2005 to August 2009, were enrolled in the study and underwent a 24-h ambulatory arterial blood pressure monitoring (ABPM). PPH has been defined as a decrease in SBP of 20mmHg within 2h after a meal.
RESULTS: : Four hundred and one patients were enrolled (mean age 77.7±11 years, males 47.7%). Hypertension was not adequately controlled in 290 (72.3%) patients. PPH was found in 292 of 401 (72.8%) patients. A value of 10mmHg or higher of SD SBP was predictive of PPH, with a sensitivity and specificity of 87 and 57%, respectively. At each meal, patients with higher SBP readings before meal had the greatest decrease in SBP (P<0.001). During the follow-up, 34 patients died for cardiovascular causes. Breakfast BP variation was the most predictive variable of cardiovascular mortality (B=0.020, P=0.04, HR 1.020, IC 1.001-1.040).
CONCLUSION: : In our population, PPH was common. A diurnal standard deviation of SBP of 10mmHg or higher was suggestive of its presence. ABPM identified breakfast BP decrease as a possible new risk factor for cardiovascular mortality.
2012
- The genetic basis of Insulin resistance. A brief review
[Articolo su rivista]
Carulli, Lucia; Nascimbeni, Fabio; Bertolotti, Marco; Loria, Paola
abstract
Insulin resistance, represents the primary physiologic defect underlying the metabolic syndrome (MS) which includes insulin resistance/hyperinsulinemia, glucose intolerance and/or type 2 diabetes mellitus, visceral obesity, hypertension, and dyslipidemia. This constellation of traits is a major risk factor of cardiovascular mortality and morbidity. Insulin sensitivity varies among individuals. Although environment, physical inactivity and caloric excess, plays an important role in the development of obesity and thus insulin resistance, several studies show that there are also a genetic influence in the development of insulin resistance. Extreme forms of insulin resistance may be caused by mutations in the genes for the insulin receptor and peroxisome proliferator-activated receptor gamma, these forms rare. The genetic basis for common more moderate forms of insulin resistance is likely to be polygenic and heterogeneous. There is evidence that gene variants may have phenotypic influences on more than one MS traits which may explain, in part, the clustering of these traits. We briefly review in this article the evidence that insulin resistance has a genetic basis. The identification of specific gene variants will help understanding the molecular basis of MS and ultimately will help to set up preventive and therapeutic intervention
2012
- The use of stable and radioactive sterol tracers as a tool to investigate cholesterol degradation to bile acids in humans in vivo
[Articolo su rivista]
Bertolotti, Marco; A., Crosignani; M., Del Puppo
abstract
Alterations of cholesterol homeostasis represent important risk factors for atherosclerosis and cardiovascular disease. Different clinical-experimental approaches have been devised to study the metabolism of cholesterol and particularly the synthesis of bile acids, its main catabolic products. Most evidence in humans has derived from studies utilizing the administration of labeled sterols; these have several advantages over in vitro assay of enzyme activity and expression, requiring an invasive procedure such as a liver biopsy, or the determination of fecal sterols, which is cumbersome and not commonly available. Pioneering evidence with administration of radioactive sterol derivatives has allowed to characterize the alterations of cholesterol metabolism and degradation in different situations, including spontaneous disease conditions, aging, and drug treatment. Along with the classical isotope dilution methodology, other approaches were proposed, among which isotope release following radioactive substrate administration. More recently, stable isotope studies have allowed to overcome radioactivity exposure. Isotope enrichment studies during tracer infusion has allowed to characterize changes in the degradation of cholesterol via the “classical” and the “alternative” pathways of bile acid synthesis. Evidence brought by tracer studies in vivo, summarized here, provides an exceptional tool for the investigation of sterol metabolism, and integrate the studies in vitro on human tissue.
2011
- Associated factors to post-operative delirium in patients with hip fractures: an orthogeriatric experience.
[Abstract in Rivista]
Bertolotti, Marco; Facchini, Mc; Garutti, Anna; Guerzoni, Valentina; Lancellotti, Giulia; Manfredini, Ilenia; Mussi, Chiara; Patti, Corrado; Resta, Gianluca; Scotto, Roberto; Squarzina, Pb; Vedele, Carmen
abstract
The aim of the study was to evaluate the incidence of post-operative delirium and associated factors in patients with hip fracture admitted to an orthogeriatric ward.
2011
- Invecchiamento e alterazioni dell’omeosatsi del colesterolo: studio dei livelli plasmatici degli steroli idrossilati come markers metabolici.
[Articolo su rivista]
Bertolotti, Marco; P., Loria; Mussi, Chiara; E., Pellegrini; M., del Puppo; C., Galbusera; S., Ognibene; Carulli, Lucia; Carulli, Nicola
abstract
Objectives: The modifications of cholesterol metabolism which associate with aging are ill-defined. The objective of this study is to define aging-associated alterations of the different metabolic pathways controlling cholesterol homeostasis by analysis of circulating levels of hydroxylated sterols.Methods: We analyzed serum samples from 123 adult subjects (45 male, 78 female, age range 38-78) from the epidemiological M.I.COL. study (Multicentrica Italiana Colelitiasi). The concentrations of the different hydroxysterols, recognized as markers of the main metabolic pathways of cholesterol homeostasis, were determined: synthesis (lathosterol), absorption (campesterol and sitosterol), degradation to bile acids (7alpha-hydroxy-4-cholesten-3-one). Analysis was performed by gas-chromatography - mass spectrometry.Results: a significant correlation was detected between age and cholesterol levels. The lathosterol/cholesterol ratio (an index of cholesterol synthesis) was lower in older (age > 65), compared to younger subjects (10239 vs 12662 microg/100 microg cholesterol; P < 0.05, t test for independent data). A significant inverse correlation was present between the lathosterol/cholesterol ratio and age. The remaining markers did not show significant modifications with aging, even if a trend toward a reduction of cholesterol markers was present.Conclusions: These data, although preliminary, show a reduction of cholesterol synthesis with aging. The finding might be related with a reduced metabolic need for cholesterol in advancing age, leading to a down-regulation of the main mechanisms of cholesterol uptake in the liver. The possible implications in terms of pharmacological management of hypercholesterolemia remain to be defined.
2011
- Risk for cardiovascular events in an Italian population of patients with type 2 diabetes
[Articolo su rivista]
E., Pellegrini; M., Maurantonio; I. M., Giannico; M. S., Simonini; Ganazzi, Dorval; Carulli, Lucia; D'Amico, Roberto; A., Baldini; Loria, Paola; Bertolotti, Marco; Carulli, Nicola
abstract
BACKGROUND AND AIM:This study aims to analyse the risk of cardiovascular events in a local cohort of patients with type 2 diabetes, and to evaluate the prognostic accuracy of four algorithms used to estimate cardiovascular risk: the Framingham study, United Kingdom Prospective Diabetes Study (UKPDS), Riskard study and Progetto Cuore.METHOD AND RESULTS:We analysed clinical charts of the Diabetes Clinics of Modena for the period 1991-95. Patients in the age range of 35-65 with type 2 diabetes and no previous cardiovascular disease were eligible. The incidence of new cardiovascular disease was compared with estimated rates deriving from the different functions. A stratification was obtained in subgroups at different cardiovascular risk, allowing comparison between the algorithms. A total of 1532 patients were eligible; women presented a worse cardiovascular risk profile. An absolute 10-year rate of cardiovascular events of 14.9% was observed. Comparing patients with events with event-free subjects, we found significant differences in systolic blood pressure, age at visit, smoking, high-density lipoprotein (HDL)-cholesterol, duration of diabetes, glycosylated haemoglobin (HbA1c) and co-morbidities. Comparing the estimated risk rate according to the different functions, Italian algorithms were more consistent with observed data; however, Progetto Cuore and Riskard show underestimation of events when applied to females.CONCLUSIONS:Estimation of cardiovascular risk is dependent on the algorithm adopted and on the baseline risk of the reference cohort. Functions designed for a specific population, including risk variables peculiar for diabetes, should be adopted to increase the performance of such functions which is clearly unsatisfactory at present.
2011
- Usefullness of a “cardiogeriatric” outpatient clinic in a third world country: an experience in Tanzania.
[Abstract in Rivista]
Bertolotti, Marco; Garutti, Anna; Manfredini, Ilenia; Mussi, Chiara; Patti, Corrado; Resta, Gianluca; Scotto, Roberto; Vedele, Carmen
abstract
The aim of the study was to describe the usefullness of a “cardiogeriatric” outpatient clinic in a third world country, in particular in a developing country like Tanzania.
2010
- Cholesterol metabolism in gallstone disease .Preliminary evidence from the analysis of circulating markers of sterol homeostasis
[Abstract in Rivista]
Pellegrini, E; Bertolotti, Marco; Loria, Paola; Del Puppo, M; Galbusera, C; Ognibene, S; Carulli, Lucia; Carulli, Nicola
abstract
Little is known on the molecular mechanisms underlying cholesterol cholelithiasis even if previous evidence has suggested that reduced production of bile acids might play a role. AIM of the present study was to analyze the hepatic expression of a number of genes involved in bile acid metabolism in human cholelithiasis. METHODS. Surgical liver biopsies were obtained in 11 patients with untreated cholesterol cholelithiasis and 9 gallstone-free subjects; mRNA levels of CYP7A1 and related nuclear receptors and coactivators were assayed by real-time quantitative RT-PCR. RESULTS. No differences were detected the expression of any of the genes studied, with the exception of PPAR-gamma coactivator 1 (PGC-1), a transcriptional coactivator of CYP7A1 involved in insulin sensitivity and energy balance, which was significantly (p < 0.01) less expressed in gallstone subjects. Expression of PGC-1 was linearly correlated with the bile acid receptor FXR in the population of gallstone patients (r = 0.87 on a log scale, p < 0.01). CONCLUSIONS. PGC-1 appears to play a role in the prevention of cholesterol gallstone disease in humans; the finding might suggest a link with insulin resistance conditions. This effect might take place via interaction with the bile acid receptor FXR, whose protective role in cholelithiasis has been suggested by recent evidence in animal models. PGC-1 and related genes might therefore represent molecular targets for the prevention and/or treatment of gallstone disease.
2010
- Invecchiamento ed alterazioni dell’omeostasi del colesterolo: studi dei livelli plasmatici degli steroli idrossilati come markers metabolici.
[Abstract in Rivista]
Bertolotti, Marco; Loria, Paola; Pellegrini, E; Mussi, Chiara; Del Puppo, M; Galbusera, G; Ognibene, S; Carulli, Lucia; Carulli, Nicola
abstract
-
2010
- Lancellotti G, Bergamini L, Finelli ME, Guerzoni V, Mannina M, Zanasi A, Facchini MC, Squarzina PB, Bertolotti M, Mussi C. Fattori associati al delirium post-chirurgico in pazienti fratturati di femore: l’esperienza in ortogeriatria.
[Abstract in Rivista]
Lancellotti, Giulia; Bergamini, Lucia; Finelli, Maria Elisa; Guerzoni, Valentina; Mannina, Massimo; Zanasi, Andrea; Facchini, Mc; Squarzina, Pb; Bertolotti, Marco; Mussi, Chiara
abstract
Il lavoro si propone di studiare le caratteristiche cliniche del delirium post-chirurgico nei pazienti anziani con frattura di femore secondaria a caduta.
2010
- Novel genetic mutation in apolipoprotein E2 homozygosis and its implication in organ donation: a case report
[Articolo su rivista]
Cautero, Nicola; DI BENEDETTO, Fabrizio; N., De Ruvo; R., Montalti; Guerrini, Gian Piero; Ballarin, Roberto; Spaggiari, Mario; Smerieri, Nazareno; DE BLASIIS, Maria Grazia; Rompianesi, Gianluca; R. M., Iemmolo; M., Marino; Bertolotti, Marco; S., Zivieri; Gerunda, Giorgio Enrico
abstract
Disorders in lipoprotein metabolism do not contraindicate liver procurement and transplantation (LT). In this circumstance, LT provides an intriguing opportunity to assess the in vivo contribution of the liver to the synthesis and degradation of genetically polymorphic plasma proteins. Apolipoprotein (APO) E exists with several common phenotypic differences due to gene polymorphism. Some authors have shown that the APOE phenotype of the recipient was virtually completely converted to that of the donor, providing evidence that >90\% of plasma APOE arises from the liver. Homozygosis for APOE2 (E2-E2) is related to an increased incidence of type III hyperlipoproteinemia (HLP). Recently, some authors have identified 4 new APOE mutations that are strongly linked to a unique entity of renal lipidosis called lipoprotein glomerulopathy (LPG). At present, 65 cases of LPG have been reported worldwide, although most patients have been discovered in Japan and other East Asian countries. We have herein reported a case of LT in a patient with advanced hepatocarcinoma who received a liver from a caucasian donor affected by type III HLP due to homozygous E2-E2. The LPG was due to a novel genetic mutation in APOE. After the LT, the recipient, developed de novo severe lipid abnormalities despite good graft function. To our knowledge this is the first report of an LT using a graft from a non Asian donor with homozygous E2-E2 with the presence of a novel APOE mutation.
2010
- Predictive factors of lack of response to antiviral therapy among in patients with recurrent hepatitis C after liver transplantation.
[Articolo su rivista]
M., Marino; R. M., Iemmolo; R., Montalti; Bertolotti, Marco; DI BENEDETTO, Fabrizio; N. D., Ruvo; Cautero, Nicola; G., Guerrini; DE BLASIIS, Maria Grazia; Gerunda, Giorgio Enrico
abstract
The current therapy for hepatitis C recurrence after liver transplantation OLT is based on interferon (IFN) and ribavirin (RBV) in monotherapy or combination. The rate of sustained virological response (SVR) varies between 10% and 45%. We have retrospectively analyzed factors that could predict SVR after antiviral therapy. We analyzed 42 patients who completed a cycle of therapy with natural or pegylated IFN plus RBV. There were 15 (35.7%) patients who obtained an SVR. The following factors were significantly associated with a lack of SVR: donor age >or=50 years (P = .046); donor body mass index (BMI) > 27 (P = .016); genotype 1 versus 2 to 3 (P = 0.010), aspartate transferase (AST) before therapy >or= 140 U/L (P = .046), alanine transferase before therapy >or= 280 U/L (P = .055), use of natural IFN versus pegylated IFN (P = .016). The only factors remaining after multivariate analysis were: donor BMI, AST before therapy and genotype. Our data confirmed that genotype 1 was associated with poorer outcomes; other additional parameters can influence the response to antiviral therapy.
2009
- Differential effect of oleic and palmitic acid on lipid accumulation and apoptosis in cultured hepatocytes
[Articolo su rivista]
Ricchi, Matteo; Odoardi, Maria Rosaria; Carulli, Lucia; Anzivino, Claudia; Ballestri, Stefano; Pinetti, Adriano; Fantoni, Luca Isaia; F., Marra; Bertolotti, Marco; S., Banni; A., Lonardo; Carulli, Nicola; Loria, Paola
abstract
BACKGROUND AND AIM: Studies have shown monounsaturated oleic acid to be less toxic than palmitic acid and to prevent/attenuate palmitic acid hepatocites toxicity in steatosis models in vitro. However, to what degree these effects are mediated by steatosis extent is unknown. METHODS: We evaluated whether steatosis per se is associated with hepatocytes apoptosis and determined the role of oleic and palmitic acid, the most abundant fatty acids in western diets, on triglyceride accumulation and apoptosis in an in vitro model of steatosis induced in three hepatocytic cell lines (HepG2, HuH7, WRL68). The impact of incubation for 24 h with oleic (0.66 and 1.32 mM) and palmitic acid (0.33 and 0.66 mM), alone or combined (molar ratio 2 : 1) on steatosis, apoptosis, and insulin signalling, was evaluated. RESULTS: Concurrent with PPARgamma and SREBP-1 gene activation, steatosis extent was larger when cells were treated with oleic than with palmitic acid; the latter fatty acid was associated with increased PPARalpha expression. Cell apoptosis was inversely proportional to steatosis deposition. Moreover, palmitic, but not oleic acid, impaired insulin signalling. Despite the higher amount of fat resulting from incubation of the two fatty acids combined, the apoptosis rate and impaired insulin signalling were lower than in cells treated with palmitic acid alone, indicating a protective effect of oleic acid. CONCLUSIONS: Oleic acid is more steatogenic but less apoptotic than palmitic acid in hepatocityc cell cultures. These data may provide a biological basis for clinical findings on dietary patterns and pathogenetic models of nonalcoholic fatty liver disease.
2009
- Do diabetes and obesity promote hepatic fibrosis in familial heterozygous hypobetalipoproteinemia?
[Articolo su rivista]
Ballestri, Stefano; Lonardo, A; Losi, L; Pellegrini, E; Bertolotti, Marco; Loria, Paola
abstract
Letter
2009
- Endocrine and liver interaction: the role of endocrine pathways in NASH
[Articolo su rivista]
Loria, Paola; Carulli, Lucia; Bertolotti, Marco; A., Lonardo
abstract
This article reviews evidence that causally links hormonal disorders with hepatobiliary disease, and gives particular focus to nonalcoholic steatohepatitis (NASH). The downstream mechanisms by which endocrine disturbances cause liver disease might be similar to those involved in the development of primary liver disease. Hypothyroidism, for example, might lead to NASH, cirrhosis and potentially liver cancer via the development of hyperlipidemia and obesity. Patients with growth hormone deficiency have a metabolic-syndrome-like phenotype that is also associated with the development of NASH. Polycystic ovary syndrome is a common endocrine disorder that is often associated with insulin resistance, the metabolic syndrome, altered levels of liver enzymes and the development of NASH. Recent findings support a role of dehydroepiandrosterone sulfate deficiency in the development of advanced NASH. In addition, adrenal failure is increasingly reported in patients with end stage liver disease and in patients who have received a liver transplant, which suggests a bidirectional relationship between liver and endocrine functions. Clinicians should, therefore, be aware of the potential role of endocrine disorders in patients with cryptogenic liver disease and of the effects of liver function on the endocrine system.
2009
- Genetic polymorphisms in subjects with Non Alcoholic Fatty Liver Disease.
[Articolo su rivista]
Carulli, Lucia; Canedi, I; Rondinella, S; Lombardini, S; Ganazzi, Dorval; Fargion, S; DE PALMA, M; Lonardo, A; Ricchi, Matteo; Bertolotti, Marco; Carulli, Nicola; Loria, Paola
abstract
BACKGROUND: Environmental and genetic factors play a role in the pathogenesis and natural history of non-alcoholic fatty liver disease (NAFLD). METHODS: In 114 subjects with NAFLD we report the prevalence and correlation with clinical parameters of three polymorphisms: interleukin-6 (-174G/C), plasma cell differentiation antigen (K121Q) and microsomal transfer protein (-493G/T). In 59 biopsied patients with NAFLD the polymorphisms were also related to histological features. RESULTS: IL-6 -174C variant was more prevalent (p<0.01) in NAFLD compared to controls. In the NAFLD group, C carriers had higher HOMA-IR and fasting insulin than G carriers (p<0.05). The prevalence of IL-6/C variant was higher (83%) in biopsied than in not biopsied subjects (66%) (p<0.05). In biopsied subjects, C carriers had higher HOMA and fasting insulin (p<0.05) compared than those with G allele. The prevalence of IL-6 -174G/C polymorphism was significantly higher in NASH than in NAFLD (p=0.048). At logistic regression analysis IL-6 -174C was an independent predictor of both NAFLD (OR 4.116, C.I. 1.126-15.048) and NASH (OR 7.035, C.I. 1.167-42.394). Conversely, the distribution of PC-1 and MTP polymorphisms was not significantly different compared to the control group, nor associated with clinical or histological characteristics. CONCLUSIONS: Our data suggest that IL-6 -174C genetic polymorphisms, involved in inflammation and insulin resistance, are associated with NASH. These data may contribute to the understanding of the genetic susceptibility to NAFLD.
2008
- APOE MODENA : A NOVEL APOE MUTANT CAUSING LIPOPROTEIN GLOMERULOPATHY
[Abstract in Rivista]
Bertolotti, Marco; Elisa, Pellegrini; Magistroni, Riccardo; Juri, Piattoni; Carulli, Lucia; Gian Paolo, Russi; Livia, Pisciotta; Sebastiano, Calandra; Stefano, Bertolini
abstract
Lipoprotein glomerulopathy (LPG) is a rare disease characterized by laminated lipid thrombi in the lumina of dilated glomerular capillaries. Apolipoproteins E and B can be demonstrated in these lipid deposits. The plasma lipid profile of LPG patients is similar to that of dysbetalipoproteinemia with elevated IDL and ApoE. Patients often present nephrotic proteinuria but their lipid profile differs from that of nephrotic syndrome secondary to other kidney diseases. LPG has been mainly reported in Japanese and Chinese subjects, associated with novel mutations in APOE gene encoding ApoE. We have identified LPG in an Italian women who at the age of 47 was found to have a combined hyperlipidemia (TC 376 and TG 306 mg/dl) and subsequently developed proteinuria in the nephrotic range. Renal biopsy demonstrated lipoprotein thrombi in glomerular capillaries suggesting LPG. The sequence of APOE gene showed that the patient was: i) homozygous for 2 allele [Cys112 and Cys158 in the mature protein] and ii) heterozygous for a novel mutation in exon 4: c.502 C>T [Arg 150>Cys in the mature protein]. Since the mutant ApoE has a new cysteine residue it is likely that it forms a disulfide bridge with the other Cys residues of the E2 isoforms, resulting in ApoE polymerization (dominant negative effect). This is probably the cause of both dyslipidemia and lipid thrombi in the glomerular capillaries. In view of the poor response of plasma lipids and renal histology and function to statin treatment, the patient started lipid-apheresis with reduction of both dyslipidemia and proteinuria.
2008
- Correlation between plasma levels of 7alpha-hydroxy-4-cholesten-3-one and cholesterol 7alpha-hydroxylation rates in vivo in hyperlipidemic patients
[Articolo su rivista]
Bertolotti, Marco; DEL PUPPO, M; Gabbi, Chiara; Corna, F; Carulli, Lucia; Pellegrini, E; Zambianchi, Lisa; Anzivino, Claudia; Ricchi, M; Loria, Paola; Kienle, Mg; Carulli, Nicola
abstract
BACKGROUND/AIM: Hepatic bile acid synthesis is the main mechanism whereby the organism can degrade cholesterol. Plasma levels of 7alpha-hydroxy-4-cholesten-3-one have been reported to reflect bile acid synthesis and the expression or activity of the limiting enzyme of the main biosynthetic pathway, cholesterol 7alpha-hydroxylase. Aim of this study was to correlate the levels of this metabolite with the rates of cholesterol 7alpha-hydroxylation in vivo, a direct measurement of bile acid synthesis, in hyperlipidemic patients. DESIGN: Concentrations of 7alpha-hydroxy-4-cholesten-3-one were assayed by gas-liquid chromatography: mass spectrometry in plasma samples obtained in 18 patients with primary hyperlipoproteinemia who previously underwent determination of cholesterol 7alpha-hydroxylation rates in vivo by tritium release analysis. Both determinations were performed in basal conditions and after treatment with hypolipidemic drugs (the fibric acid derivatives gemfibrozil and bezafibrate, cholestyramine alone or associated with simvastatin). RESULTS: Changes in plasma 7alpha-hydroxy-4-cholesten-3-one profile closely reflected in vivo cholesterol 7alpha-hydroxylation rates during treatment with fibrates, cholestyramine and cholestyramine plus simvastatin. When plotting determinations from all studies (n=40), a very strict correlation was disclosed between plasma 7alpha-hydroxy-4-cholesten-3-one and cholesterol 7alpha-hydroxylation rates (r=0.81, P<0.001). CONCLUSIONS: Plasma 7alpha-hydroxy-4-cholesten-3-one closely mirrors measurements of cholesterol 7alpha-hydroxylation rates in vivo in hyperlipidemic subjects and therefore stands as a reliable marker of global bile acid synthesis. In view of the correlation observed, these data may help to interpret changes of plasma levels of this metabolite in terms of cholesterol balance quantification.
2008
- ESTIMATION OF CARDIOVASCULAR RISK IN TYPE 2 DIABETES
[Abstract in Rivista]
E., Pellegrini; Simonini, M. S.; M., Maurantonio; I. M., Giannico; D'Amico, Roberto; Ganazzi, Dorval; Carulli, Lucia; Loria, Paola; Bertolotti, Marco; Carulli, Nicola
abstract
Diabetes mellitus is a major risk factor for cardiovascular (CV) events. Many algorithms have been devised to assess CV risk, some of which specific for diabetics. Most of them, however, can hardly be extrapolated to Mediterranean countries. AIM of this study was to analyze CV risk and the incidence of CV events in a local cohort of patients with type 2 diabetes. METHODS. Clinical charts of the Diabetes Clinics of Modena in the period 1991-1995 were analyzed. Patients aged 35-65 with type 2 diabetes and no previous CV disease were eligible. Global CV risk was computed according to Framingham, RISCARD, Progetto Cuore and UKPDS algorithms and compared with the actual rate of CV events over the following 10 years. RESULTS. 2416 patients were screened; 1532 of them (63.4%) were eligible on the basis of predefined criteria and completeness of data. In such population an absolute 10-yr risk rate of 14.6% was observed. When looking at the characteristics of the patients who developed a cardiovascular event compared to those who did not, we found a significant difference in the prevalence of risk factors as systolic blood pressure, age at visit, smoke, duration of diabetic disease and HbA1c. COPD and chronic heart failure also display a higher prevalence in patients with events, suggesting a possible role of these chronic conditions in developing cardiovascular disease. Interestingly, most of the subjects presenting with a CV event had a low to moderate risk estimate at the beginning; this was particularly evident with the Progetto Cuore algorithm. CONCLUSIONS. Estimation of CV risk is largely dependent on the algorithm adopted and on the baseline risk of the reference cohort. Equations designed for a specific population should be adopted. The overall performance of presently available functions is however low. Inclusion of additional risk parameters might hopefully increase the performance of such algorithms, which is presently clearly unsatisfactory. The algorithm derived from the present study will be utilized for a prospective evaluation of CV risk in our local cohort.
2008
- INCREASED 27-HYDROXYLATION OF CHOLESTEROL IN PRIMARY HYPERCHOLESTEROLEMIA
[Abstract in Rivista]
Bertolotti, Marco; M., Del Puppo*; C., Gabbi; Anzivino, Claudia; Carulli, Lucia; M., Galli Kienle*; Carulli, Nicola
abstract
BACKGROUND. The first step in the alternate biosynthetic pathway of bile acid synthesis from cholesterol is represented by hydroxylation on cholesterol side chain, and is catalyzed by the mitochondrial enzyme 27-hydroxylase, which is present both in liver and in extrahepatic tissues. The physiological relevance of such pathway is still unknown, even if it is believed to play a role in the degradation of cholesterol outside the liver, possibly in the vessel wall (1).AIM of the present study was to investigate the rates of cholesterol 27-hydroxylation “in vivo” in patients with primary hypercholesterolemia, and to assess the effects induced by treatment with statin drugs.METHODS. Seven patients with primary hypercholesterolemia (FH or polygenic hypercholesterolemia) underwent determination of cholesterol 27-hydroxylation rates “in vivo” by means of continuous i.v. infusion of deuterated 27-hydroxycholesterol over 2 hr. Plasma deuterated 27-hydroxycholesterol was assayed after standard sterol extraction by gas chromatography-mass spectrometry (GC-MS) with 19-hydroxycholesterol as an internal standard. The rate of production of 27-hydroxycholesterol was calculated as the ratio between isotope enrichment and infusion rate (1,2). The data were compared with those obtained in a population of 4 normocholesterolemic controls. In some patients the infusions were repeated during treatment with standard doses of atorvastatin (5 infusions) or rosuvastatin (5 infusions).RESULTS. The rates of 27-hydroxylation were significantly higher in untreated hypercholesterolemic patients, compared with controls (8.7±2.7 mg/h vs 3.7±1.2 mg/h, mean ± SD, p < 0.01). After treatment with statins, hydroxylation rates dropped by nearly 50% along with a drastic reduction in plasma total and LDL-cholesterol, so that the ratio between 27-hydroxylation rates and plasma cholesterol was unchanged. No difference was detectable between the two statins. Linear regression analysis showed a correlation trend between plasma cholesterol and 27-hydroxylation rates.CONCLUSIONS. Primary hypercholesterolemia associates with increased rates of cholesterol 27-hydroxylation, which tend to normalize during hypocholesterolemic treatment with statins. The correlation between plasma cholesterol levels and 27-hydroxylation support the view that the latter may act as a compensatory mechanism in a condition of larger plasma cholesterol pool. A regulatory role for hepatic and extrahepatic nuclear receptors seems reasonable. These data might encourage novel pharmacological approaches for the management of hypercholesterolemia and the prevention of atherosclerosis.
2008
- Increase degradation of cholesterol via the alternate pathway of bile acid biosynthesis in primary hypercholesterolemia.
[Abstract in Rivista]
Bertolotti, Marco; Del Puppo, M; Gabbi, C; Anzivino, Claudia; Carulli, Lucia; Galli Kienle, M; Carulli, N.
abstract
Priamry hyeprcholesterolemai associates with increased rates of cholesterol 27 hydroxylation which normalizes with statin treatment. the correlation between plasma cholesterol levels and 27 hydroxylation support the view that the latter may act as a compensatory mechanism in a condition of larger plasma cholesterol pool. A regulatory roel for uclear receptors seems reasonable.These dta may encourage novel pharmacplogical approaches for the managment of hypercholesterolemia and prevention of atherosclerosis
2008
- La calcolosi biliare.
[Articolo su rivista]
Bertolotti, Marco; Carulli, Lucia
abstract
Articolo di review sulla calcolosi biliare
2008
- NAFLD AND TYPE 2 DIABETES: A GENETIC OR METABOLIC ISSUE?
[Abstract in Rivista]
Rondinella, S; Carulli, Lucia; Rudilosso, A; Ganazzi, D; Bertolotti, Marco; Loria, Paola; Carulli, Nicola
abstract
BackgroundType 2 diabetes (T2D) seems to be a risk factor for the development of Non Alcoholic Fatty Liver Disease (NAFLD) and for its progression to fibrosis. The pathogenesis of the NAFLD-T2D association is not known. Recent data have shown that hyperinsulinemia and insulinresistance (IR) may be the primary phenomenon in NAFLD as well as inflammation.Aim of the study was to evaluate the prevalence of NAFLD in T2D, to correlate NAFLD with the Metabolic Syndrome (MetS) features and with T2D therapy, to evaluate the relation between NAFLD and genetic polymorphisms associated to IR, PC-1 K121Q, and inflammation, IL-6–174 C/G.Methods80 diabetic subjects were enrolled and underwent blood sample and medical history to ruled out alcohol consumption and other liver diseases aetiology. Steatosis was defined according to standardized ultrasonographic criteria and a score for each criterion was assigned like indicator of the severity of fatty liver infiltration (Fatty liver indicator, FLI).ResultsThe subjects studied were overweight with BMI=28.60 (25°÷ 75°=25.35÷ 32.95), had normal lipid profile and uric acid and had higher GPT levels (25°÷ 75°; GOT: 7.00÷ 27.25 and GPT: 21.00÷38.00)22.5% subjects had no steatosis whereas 77.5% had different severity of fatty liver infiltrationFLI did correlate significantly with BMI (p< 0.01), total Cholesterol (p<0.01), glycosilated haemoglobin (p<0.05) and TG (p<0.01)No correlation was found between T2D therapy and severity of NAFLD.No significant difference in polymorphisms prevalence was observed when NAFLD subjects were compared to a control group.DiscussionOur data show that T2D patients have a very high prevalence of NAFLD which is probably related to hyperinsulinism and IR. This is further supported by the positive correlation of NAFLD with BMI and TG. The lipogenic effects of insulin may underlie such relationship. In our population NAFLD associates with some features of MetS whereas no significant genetic component is present.
2008
- Nonalcoholic fatty liver disease induced by leuprorelin acetate
[Articolo su rivista]
Gabbi, C.; Carubbi, Francesca; Losi, L.; Loria, Paola; Costantini, M.; Bertolotti, Marco; Carulli, N.
abstract
Leuprorelin acetate is an agonist of gonadotropinreleasinghormone, used as a first choice treatment in patientswith prostate carcinoma. The impact of leuprorelin therapy inliver function and metabolism is largely unknown. We reportabout a patient who had been treated for 32 months withleuprorelin acetate, who developed a nonalcoholic fatty liverdisease (NAFLD), associated with a focal lesion at the IVhepatic segment where histologic features appeared to be moresevere. The patient, in addition to NAFLD, presented a markediatrogenic hypotestosteronemia and full-criteria meeting thediagnosis of metabolic syndrome, including insulin resistance.The radiologic and clinical findings, the histopathologicfeatures, and the absence of any hepatic abnormalities beforetreatment, support a causal role of leuprorelin in inducingmetabolic derangement that, most likely secondary to androgendeprivation, were, in turn, responsible for the development of NAFLD. This is the first case report of NAFLDwith focal fatty liver associated with leuprorelin therapy.Patients in leuprorelin should be carefully monitored for thedevelopment of liver disease.
2008
- Nuclear receptors and obstructive cholestasis in Humans: increased heaptic expression of short heterodimer partner : a protective response?
[Abstract in Rivista]
Bertolotti, Marco; Gabbi, Chiara; Anzivino, C; Baldelli, Enrica; Carulli, Lucia; Carulli, Nicola
abstract
alteration in hepatic expression of nuclear receptors durinhg obstructive cholestasis, appear to be mediated by increaased expression of SHPa nd appear to be finalized to stimulate extrusion of biliary lipid out of teh liver and to inhibit further uptake of organic anions into the liver cell itself.
2008
- Nuclear receptors as potential molecular targets in cholesterol accumulation conditions: Insights from evidence on hepatic cholesterol degradation and gallstone disease in humans
[Articolo su rivista]
Bertolotti, Marco; Gabbi, C; Anzivino, Claudia; Carulli, Lucia; Loria, Paola; Carulli, Nicola
abstract
The liver plays a central role in the regulation of cholesterol homeostasis. Hepatic cholesterol content is maintained by a complex interplay between input and output pathways; alterations in the balance among these processes may lead to accumulation of excess cholesterol in body compartments with potentially deleterious consequences at the level of blood vessels (atherosclerosis) and biliary tract (gallstone disease). Molecular biology has brought new insights into this field. Nuclear receptors have been shown to play a key role in the "sensing" of intracellular cholesterol levels and in the triggering of metabolic responses via the sterol regulatory element binding protein (SREBP) cascade. A nuclear receptor for bile acids, farnesoid X receptor (FXR), has been identified and the molecular pathways underlying feedback inhibition of bile acid synthesis, the main mechanism of irreversible degradation of cholesterol, have been clarified. Such regulation involves a number of additional coactivators/corepressors of the transcription of the limiting enzyme of bile acid synthesis, cholesterol 7alpha-hydroxylase. Finally, the main transporters of biliary lipids (bile acids, phospholipids and cholesterol) have been described; most of them undergo transcriptional control by nuclear receptors, allowing regulation of biliary lipid efflux in conditions of different intracellular availability. Despite a body of evidence coming from experimental models the intimate mechanisms of regulation have not been clearly defined and direct evidence in humans is rather limited. This review will focus on the role of nuclear receptors in the regulation of hepatic cholesterol degradation and biliary lipid secretion, and on the theoretical applications from a pharmacotherapeutic perspective.
2008
- Olanzapine metabolic side effects: a weight gain issue?
[Articolo su rivista]
Carulli, Lucia; F., Mazzi; S., Rondinella; Bertolotti, Marco
abstract
Case report
2008
- Reply
[Articolo su rivista]
Bertolotti, Marco; C., Gabbi; Anzivino, Claudia; Carulli, Lucia; Carulli, Nicola
abstract
Letter reply
2008
- TYPE 2 DIABETES AND CARDIOVASCULAR EVENTS : STUDY OF THE AMIN RISK FACTORS IN A LOCAL POPULATION OF PATIENTS
[Abstract in Rivista]
Elisa, Pellegrini; M., Sole Simonini; Mauro, Maurantonio; Iolanda M., Giannico; Carulli, Lucia; D'Amico, Roberto; Dorval, Ganazzi; Loria, Paola; Bertolotti, Marco; Carulli, Nicola
abstract
Background and aim. The aim of this study is to analyze the risk of cardiovascular events in a local cohort of patients with type 2 diabetes, and to evaluate the prognostic accuracy of four algorithms used to estimate cardiovascular risk: Framingham study, UKPDS study, Riskard study and Progetto Cuore. Method and results. We analyzed clinical charts of the Diabetes Clinics of Modena during the period 1991-1995. Patients aged 35-65 with type 2 diabetes and no previous cardiovascular disease were eligible. The incidence of new cardiovascular disease was compared with estimated rates deriving from the different functions. A stratification was obtained in subgroups at different cardiovascular risk, allowing comparison between the algorithms. The presence of heart failure and chronic obstructive pulmonary disease was also recorded. 1532 patients were eligible; women presented a worse cardiovascular risk profile. An absolute 10-yr rate of cardiovascular events of 14.9% was observed. Comparing patients with events with event-free subjects we found significant differences in systolic blood pressure, age at visit, smoke, HDL-cholesterol, duration of diabetes, HbA1c and comorbidities. Comparing the estimated risk rate according to the different functions, Italian algorithms were more consistent with observed data; however, Progetto Cuore shows underestimation of events, particularly when applied to females.Conclusions. Estimation of cardiovascular risk is dependent on the algorithm adopted and on the baseline risk of the reference cohort. Functions designed for a specific population, including risk variables peculiar for diabetes should be adopted to increase the performance of such functions which is presently clearly unsatisfactory.
2008
- Variable phenotypic expression of homozygous familial hypobetalipoproteinaemia due to novel APOB gene mutations
[Articolo su rivista]
E., Di Leo E; Magnolo, Antonia Lucia; Bertolotti, Marco; M., Bourbon; S., Carmo Pereira; M., Pirisi; CALANDRA BUONAURA, Sebastiano; Tarugi, Patrizia Maria
abstract
Homozygous familial hypobetalipoproteinaemia (Ho-FHBL) is a rare co-dominant disorder characterized by extremely low levels of low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB). Most patients with Ho-FHBL have mutations in APOB gene resulting in truncated apoBs. Some patients are asymptomatic, while others have fatty liver, intestinal fat malabsorption and neurological dysfunctions. We investigated three adult subjects with severe hypobetalipoproteinaemia and a family history of FHBL. Proband FHBL-47 had liver cirrhosis with hepatocarcinoma and a renal carcinoma but no clinical manifestations related to FHBL. He was a compound heterozygote for a 7-bp deletion in exon 21 and a base insertion in exon 26 resulting in truncated apoBs (apoB-22.46/apoB-66.51). Proband FHBL-53, with severe hepatic steatosis and fibrosis, had a nonsense mutation in exon 19 resulting in a truncated apoB (apoB-20.61) and a rare nucleotide substitution in intron 14 (c.2068-4T>A). The latter was also present in her daughter, found to have low plasma LDL-C and apoB. Proband FHBL-82 had chronic diarrhoea and steatorrhoea. She was found to be homozygous for a nonsense mutation in exon 24 resulting in a truncated apoB (apoB-26.65). In adult subjects, the presence of chronic liver disease and chronic diarrhoea, when associated with severe hypobetalipoproteinaemia, may lead to the diagnosis of Ho-FHBL.
2007
- Age-related changes in bile acid synthesis and hepatic nuclear receptor expression
[Articolo su rivista]
Bertolotti, Marco; Gabbi, C; Anzivino, Claudia; Crestani, M; Mitro, N; Del Puppo, M; Godio, C; De Fabiani, E; Macchioni, D; Carulli, Lucia; Rossi, Aldo; Ricchi, M; Loria, P; Carulli, Nicola
abstract
BACKGROUND:Recent data highlighted the role of nuclear receptors in the transcriptional regulation of the limiting enzyme of bile acid synthesis, cholesterol 7alpha-hydroxylase, in cellular and animal models. This study was designed to analyze the effects of age on cholesterol 7alpha-hydroxylase and related nuclear receptor expression in human livers.DESIGN:Surgical liver biopsies were obtained in 23 patients requiring operation on the gastrointestinal tract. mRNA levels of cholesterol 7alpha-hydroxylase and related nuclear receptors and co-activators were assayed by quantitative real-time RT-PCR. Serum levels of 7alpha-hydroxy-4-cholesten-3-one, a marker of bile acid synthesis, were assayed by gas-liquid chromatography:mass spectrometry.RESULTS:Ageing was inversely correlated with serum 7alpha-hydroxy-4-cholesten-3-one and with cholesterol 7alpha-hydroxylase mRNA levels (r = -0.44 and r = -0.45 on a semi-log scale, respectively, P < 0.05). Among different nuclear factors, cholesterol 7alpha-hydroxylase mRNA best correlated with hepatocyte nuclear factor-4 (r = 0.55 on a log scale, P < 0.05); hepatocyte nuclear factor-4 levels were also inversely correlated with age (r = -0.64 on a semi-log scale, P < 0.05). Age was inversely correlated with serum insulin-like growth factor-I levels, which were directly correlated with hepatocyte nuclear factor-4 and cholesterol 7alpha-hydroxylase expression. No suppressive effect of short heterodimer partner expression on cholesterol 7alpha-hydroxylase was observed.CONCLUSIONS:Ageing associates with reduced bile acid synthesis, possibly related to decreased hepatic expression of hepatocyte nuclear factor-4 and consequently of cholesterol 7alpha-hydroxylase. Age-related modifications of the growth hormone/insulin-like growth factor axis might play a role. These findings may help to elucidate the pathophysiology of age-related modifications of cholesterol metabolism.
2007
- Changes in bile acid synthesis in gallstone disease: cause, consequence or neither?
[Articolo su rivista]
Bertolotti, Marco; Gabbi, Chiara; Anzivino, Claudia; Carulli, Lucia; Carulli, Nicola
abstract
nd
2007
- HEPATIC EXPRESSION OF NUCLEAR RECEPTORS AND BILIARY TRANSPOTERS IN HUMAN CHOLESTEROL GALLSTONE DISEASE.
[Abstract in Rivista]
Bertolotti, Marco; Gabbi, C; Anzivino, Claudia; Tagliafico, Enrico; Carulli, Lucia; Ricchi, M; Rossi, A; Loria, Paola; Carulli, Nicola
abstract
Little is known on the molecular mechanisms underlying cholesterol cholelithiasis even if previous evidence has suggested that reduced production of bile acids might play a role. AIM of the present study was to analyze the hepatic expression of a number of genes involved in bile acid metabolism in human cholelithiasis. METHODS. Surgical liver biopsies were obtained in 11 patients with untreated cholesterol cholelithiasis and 9 gallstone-free subjects; mRNA levels of CYP7A1 and related nuclear receptors and coactivators were assayed by real-time quantitative RT-PCR. RESULTS. No differences were detected the expression of any of the genes studied, with the exception of PPAR-gamma coactivator 1 (PGC-1), a transcriptional coactivator of CYP7A1 involved in insulin sensitivity and energy balance, which was significantly (p < 0.01) less expressed in gallstone subjects. Expression of PGC-1 was linearly correlated with the bile acid receptor FXR in the population of gallstone patients (r = 0.87 on a log scale, p < 0.01). CONCLUSIONS. PGC-1 appears to play a role in the prevention of cholesterol gallstone disease in humans; the finding might suggest a link with insulin resistance conditions. This effect might take place via interaction with the bile acid receptor FXR, whose protective role in cholelithiasis has been suggested by recent evidence in animal models. PGC-1 and related genes might therefore represent molecular targets for the prevention and/or treatment of gallstone disease.
2007
- HEPATIC NUCLEAR RECEPTOR EXPRESSION AND REGULATION OF BILE ACID SYNTHESIS IN HUMANS
[Abstract in Rivista]
Bertolotti, Marco; C., Gabbi; Anzivino, Claudia; M., Crestani; E., Defabiani; Tagliafico, Enrico; Carulli, Lucia; M., Ricchi; Loria, Paola; Carulli, Nicola
abstract
Bile acid synthesis plays a crucial role in cholesterol homeostasis. Recent evidence has highlighted the role of nuclear receptors in the regulation of the expression and activity of cholesterol 7alpha-hydroxylase (CYP7A1), the limiting enzyme, in cellular and animal models. Understanding the regulatory role of nuclear receptors in humans might help to define molecular targets for pharmacological intervention aimed to enhance hepatic cholesterol degradation. AIM of the present study was to analyze the expression of CYP7A1 and a number of related nuclear receptors in human liver. METHODS. Surgical liver biopsies were obtained in 40 patients; 30 of them were untreated, presenting gallbladder stones (12), non-metastatic abdominal cancer (10) or obstructive cholestasis (8); 10 subjects were receiving standard dose of CDCA (3), UDCA (5) or cholestyramine (2). mRNA levels of CYP7A1 and of the main nuclear receptors involved in its regulation (FXR, SHP, LRH-CPF-1, HNF-4, PGC-1) were assayed by real-time RT-PCR, using custom-designed primers and with sybr-green as an intercalator of double-stranded DNA. RESULTS. CYP7A1 mRNA showed a high degree of variability. No difference was detected between untreated gallstone and gallstone-free subjects regarding the expression of CYP7A1 and other genes, with the exception of PGC-1 which was significantly (p < 0.05 on a log scale) less expressed in gallstone subjects. In untreated, non-cholestatic subjects no correlation could be detected between CYP7A1 or other genes and age. Stepwise regression analysis of data from all non-cholestatic subjects, with CYP7A1 mRNA levels as the dependent variable, showed the strongest correlation with HNF-4 as the independent variable (r = 0.471 on a log scale, p < 0.05), all other genes (including SHP) bringing non-significant further contribution to the correlation. A very strong direct correlation (r = 0.880 on a log scale, p< 0.05) was detected between HNF-4 and LRH-CPF-1 expression. Finally, no difference was observed between cholestatic and non-cholestatic patients.CONCLUSIONS. Our data suggest that HNF-4 might play a relevant role in the regulation of CYP7A1 transcription in humans; on the other hand no evidence for a suppressive role of SHP, which was well documented in cellular models, was observed. As a whole, the interrelationships between the different nuclear receptors, and their physiological role, have still to be defined. Data on CYP7A1 expression support the view that post-transcriptional, and possibly post-translational levels of regulation may also play a critical role in the control of bile acid synthesis.
2007
- Is cholangiocarcinoma another complication of insulin resistance: A report of three cases
[Articolo su rivista]
Michelini, E; Lonardo, A; Ballestri, Stefano; Costantini, M; Caporali, C; Bonati, Me; Bertolotti, Marco; Iori, R; Loria, Paola
abstract
Background: Cholangiocarcinoma is the second most common primary liver cancer, and the number of cases of intrahepatic cholangiocarcinoma (ICC) have been steadily increasing worldwide. Although the reasons for this surge are unknown, insulin resistance (IR) could be a risk factor, similar to what has been reported for other cancers. Case Report: We report on 3 cases of ICC arising in subjects sharing IR as an underlying risk factor. Case 1 was an obese and dyslipidemic patient with NAFLD. The second and the third patients were affected by type 2 diabetes. Conclusions: Evidence for a link between IR and onset of cholangiocarcinoma in our patients rests on three lines of evidence: epidemiological, biological, and exclusion of others risk factors. Studies are needed to confirm our hypothesis that IR is a risk factor for the development of ICC.
2007
- NAFLD AND TYPE 2 DIABETES: A GENETIC OR METABOLIC ISSUE?
[Abstract in Rivista]
Carulli, Lucia; Rondinella, S; Rudilosso, A; Ganazzi, D; Bertolotti, Marco; Loria, Paola; Carulli, Nicola
abstract
BackgroundType 2 diabetes (T2D) seems to be a risk factor for the development of Non Alcoholic Fatty Liver Disease (NAFLD) and for its progression to fibrosis. The pathogenesis of the NAFLD-T2D association is not known. Recent data have shown that hyperinsulinemia and insulinresistance (IR) may be the primary phenomenon in NAFLD as well as inflammation.Aim of the study was to evaluate the prevalence of NAFLD in T2D, to correlate NAFLD with the Metabolic Syndrome (MetS) features and with T2D therapy, to evaluate the relation between NAFLD and genetic polymorphisms associated to IR, PC-1 K121Q, and inflammation, IL-6–174 C/G.Methods80 diabetic subjects were enrolled and underwent blood sample and medical history to ruled out alcohol consumption and other liver diseases aetiology. Steatosis was defined according to standardized ultrasonographic criteria and a score for each criterion was assigned like indicator of the severity of fatty liver infiltration (Fatty liver indicator, FLI).ResultsThe subjects studied were overweight with BMI=28.60 (25°÷ 75°=25.35÷ 32.95), had normal lipid profile and uric acid and had higher GPT levels (25°÷ 75°; GOT: 7.00÷ 27.25 and GPT: 21.00÷38.00)22.5% subjects had no steatosis whereas 77.5% had different severity of fatty liver infiltrationFLI did correlate significantly with BMI (p< 0.01), total Cholesterol (p<0.01), glycosilated haemoglobin (p<0.05) and TG (p<0.01)No correlation was found between T2D therapy and severity of NAFLD.No significant difference in polymorphisms prevalence was observed when NAFLD subjects were compared to a control group.DiscussionOur data show that T2D patients have a very high prevalence of NAFLD which is probably related to hyperinsulinism and IR. This is further supported by the positive correlation of NAFLD with BMI and TG. The lipogenic effects of insulin may underlie such relationship. In our population NAFLD associates with some features of MetS whereas no significant genetic component is present.
2007
- Olanzapine-induced hypertriglyceridemia and Diabetes mellitus
[Abstract in Rivista]
Carulli, Lucia; Simonini, Ms; Maurantonio, M; Bertolotti, Marco; Carulli, Nicola
abstract
BackgroundHypertriglyceridemia (HTG), weight gain and new onset diabetes mellitus (DM) are documented side effects of olanzapine (OLZ). Case reports of OLZ-induced ketoacidosis with DM has been recently described. Weight gain often does not correlate with the severity of HTG and/or DM observed and it is difficult to delineate the direct effects of OLZ versus those associated with OLZ–induced obesity.We report a case showing improvement of lipid and glucose metabolism after discontinuation of OLZ, independent of body weight.Case recordA 36 years old white man had a 5 years history of hospitalizations for schizophrenia, with unremarkable lipid and glucose profile prior to initiation OLZ in October 2006. He had weight 90 Kg and BMI 33 Kg/m2. He initiated OLZ and started losing weight, with polydipsia and polyuria; in February 2007 a blood test disclosed HTG (1151 mg/dl), hyperglycemia (463 mg/dl), glycosuria (8902 mg/dl) and ketonuria (80 mg/dl). A subsequent blood test upon hospital admission showed TG=3298 mg/dl, glycated haemoglobin A1C=14.3%. His body weight was 76 Kg, BMI 27 Kg/m2 and waist circumference 90 cm. Serum insulin, serum and urinary C peptide, serum amylases and lipases and abdomen CT scan did not show any alteration.OLZ was discontinued and the patient put on insulin therapy and hydration. After one week we observed a complete remission of HTG (176 mg/dl) and improvement of glucose metabolism (glycaemia=249 mg/dl, glycosuria=652 mg/dl). A month after discharge, he still presented hyperglycaemia.ConclusionOur case demonstrates changes in OLZ-related HTG and DM unrelated to weight gain. The patient had no other cause of HTG so OLZ appeared to have a direct effect on lipid metabolism independently of weight gain. He had a family history of DM and it’s possible that the OLZ acted on a DM susceptibility. Future research is needed in order to understand the mechanisms related to glucose and lipid metabolism of atypical antipsychotic drugs.
2007
- RISK FOR CARDIOVASCULAR EVENTS IN A LOCAL POPULATION OF DIABETIC PATIENTS
[Abstract in Rivista]
Elisa, Pellegrini; Iolanda M., Giannico; Mauro, Maurantonio; D'Amico, Roberto; Dorval, Ganazzi; Augusto, Baldini; Carulli, Lucia; Bertolotti, Marco; Loria, Paola; Carulli, Nicola
abstract
AbstractBackground and aim. The aim of this study is to analyze the risk of cardiovascular events in a local cohort of patients with type 2 diabetes, and to evaluate the prognostic accuracy of four algorithms used to estimate cardiovascular risk: Framingham study, UKPDS study, Riskard study and Progetto Cuore. Method and results. We analyzed clinical charts of the Diabetes Clinics of Modena during the period 1991-1995. Patients aged 35-65 with type 2 diabetes and no previous cardiovascular disease were eligible. The incidence of new cardiovascular disease was compared with estimated rates deriving from the different functions. A stratification was obtained in subgroups at different cardiovascular risk, allowing comparison between the algorithms. 1532 patients were eligible; women presented a worse cardiovascular risk profile. An absolute 10-yr rate of cardiovascular events of 14.9% was observed. Comparing patients with events with event-free subjects we found significant differences in systolic blood pressure, age at visit, smoke, HDL-cholesterol, duration of diabetes, HbA1c and comorbidities. Comparing the estimated risk rate according to the different functions, Italian algorithms were more consistent with observed data; however, Progetto Cuore shows underestimation of events, particularly when applied to females.Conclusions. Estimation of cardiovascular risk is dependent on the algorithm adopted and on the baseline risk of the reference cohort. Functions designed for a specific population, including risk peculiar for diabetes should be adopted to increase the performance of such functions which is presently clearly unsatisfactory.
2007
- RISK FOR CARDIOVASCULAR EVENTS IN AN ITALIAN POPULATION OF PATIENTS WITH TYPE 2 DIABETES
[Abstract in Rivista]
Elisa, Pellegrini; Mauro, Maurantonio; Iolanda M., Giannico; M., Sole Simonini; Dorval, Ganazzi; Carulli, Lucia; D'Amico, Roberto; Augusto, Baldini; Loria, Paola; Bertolotti, Marco; Carulli, Nicola
abstract
Background and aim. The aim of this study is to analyze the risk of cardiovascular events in a local cohort of patients with type 2 diabetes, and to evaluate the prognostic accuracy of four algorithms used to estimate cardiovascular risk: Framingham study, UKPDS study, Riskard study and Progetto Cuore. Method and results. We analyzed clinical charts of the Diabetes Clinics of Modena during the period 1991-1995. Patients aged 35-65 with type 2 diabetes and no previous cardiovascular disease were eligible. The incidence of new cardiovascular disease was compared with estimated rates deriving from the different functions. A stratification was obtained in subgroups at different cardiovascular risk, allowing comparison between the algorithms. 1532 patients were eligible; women presented a worse cardiovascular risk profile. An absolute 10-yr rate of cardiovascular events of 14.9% was observed. Comparing patients with events with event-free subjects we found significant differences in systolic blood pressure, age at visit, smoke, HDL-cholesterol, duration of diabetes, HbA1c and comorbidities. Comparing the estimated risk rate according to the different functions, Italian algorithms were more consistent with observed data; however, Progetto Cuore shows underestimation of events, particularly when applied to females.Conclusions. Estimation of cardiovascular risk is dependent on the algorithm adopted and on the baseline risk of the reference cohort. Functions designed for a specific population, including risk peculiar for diabetes should be adopted to increase the performance of such functions which is presently clearly unsatisfactory.
2007
- Statins and HCV: a complex issue
[Articolo su rivista]
Lonardo, A; Loria, Paola; Bertolotti, Marco; Carulli, Nicola
abstract
Letter
2006
- 17 Beta-estradiol prevents cytotoxicity from hydrophobic bile acids in HepG2 and WRL-68 cell cultures
[Articolo su rivista]
M., Ricchi; Bertolotti, Marco; C., Anzivino; Carulli, Lucia; I., Canedi; Ml, Bormioli; Tiozzo, Roberta; Croce, Maria Antonietta; A., Lonardo; N., Carulli; P., Loria
abstract
Background: Epidemiological and clinical studies suggest the possibility that estrogens might have a cytoprotective effect on the liver. The aim of the present study was to test the hypothesis that 17 beta-estradiol (E-2) prevents hepatocellular damage induced by deoxycholic acid (DCA), a hydrophobic bile acid. Methods:HepG2 cells were exposed for 24 h to DCA (350 mu mol/L). Cell viability, aspartate aminotransferase and lactate dehydrogenase activity and apoptosis were measured as indices of cell toxicity. The effect of DCA was compared to that observed using either a hydrophilic bile acid, ursodeoxycholic acid (UDCA; 100 mu mol/L), or E-2 at different concentrations (1 nmol/L, 10 nmol/L, 50 nmol/L and 50 mu mol/L) or mixtures of E-2/DCA or UDCA/DCA. The same experiments were performed using WRL-68 cells that, at variance with HepG2, express a higher level of nuclear estrogen receptor. Results:High concentrations of E-2 and UDCA prevented DCA-induced decrease in cell viability, increase in enzyme activity and apoptosis evaluated both by 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) and TdT-mediated dUTP nick-end labeling (TUNEL) assays. In addition, DCA-related apoptosis, assessed by caspase activity, was also prevented by E-2 (P < 0.01) in physiological (1-10 nmol/L) doses. The cytoprotective effects of E-2 and UDCA was also observed in the WRL-68 cell line. Conclusions: 17 beta-Estradiol prevents DCA-induced cell damage in HepG2 and WRL-68 cell lines to an extent comparable to UDCA. The hypothesis that the protective effect of E-2 may be mediated by a mechanism that is nuclear estrogen receptor independent, deserves further verification.
2006
- Acute abdomen associated with schistosomiasis of the appendix
[Articolo su rivista]
Gabbi, C.; Bertolotti, M.; Iori, R.; Rivasi, F.; Stanzani, C.; Maurantonio, M.; Carulli, N.
abstract
2006
- Decreased hepatic expression of PPAR-gamma coactivator-1 in cholesterol cholelithiasis.
[Articolo su rivista]
Bertolotti, Marco; Gabbi, C; Anzivino, Claudia; Mitro, N; Godio, C; De Fabiani, E; Crestani, M; Del Puppo, M; Ricchi, M; Carulli, Lucia; Rossi, Aldo; Loria, Paola; Carulli, Nicola
abstract
Cholesterol cholelithiasis (gallstone disease) is a common disease in the Western world. The aim of the present study was to analyze the hepatic expression of a number of nuclear receptors involved in bile acid metabolism in human cholesterol gallstone disease. Surgical liver biopsies were obtained from 11 patients with untreated cholesterol cholelithiasis and nine gallstone-free subjects; mRNA levels of cholesterol 7 alpha-hydroxylase (CYP7A1) and related nuclear receptors and coactivators were assayed by quantitative real-time RT-PCR. No differences between the two groups were detected in mRNA levels of CYP7A1 and related nuclear receptors, with the exception of peroxysome proliferator-activated receptor-gamma coactivator 1 (PGC-1), which was significantly (P < 0.01) less expressed in gallstone subjects. Expression of PGC-1 was linearly correlated with farnesoid X receptor (FXR) in gallstone patients (r = 0.87 on a log scale, P < 0.01), but not in control subjects; in gallstone patients PGC-1 expression was also correlated with hepatocyte nuclear factor 4 (HNF-4) (r = 0.78, P < 0.01). These findings suggest that PGC-1 can play a role in the prevention of cholesterol gallstone disease in humans; this might take place via interaction with the bile acid receptor FXR, whose protective role in cholelithiasis has been suggested by recent evidence in animal models and other coactivators. The present data might help to understand the pathophysiology and possibly focus on new therapeutical targets in cholesterol gallstone disease.
2006
- Fatty liver, carotid disease and gallstones: A study ofage-related associations
[Articolo su rivista]
Amedeo, Lonardo; Silvia, Lombardini; Federica, Scaglioni; Stefano, Ballestri; Anna Maria, Verrone; Bertolotti, Marco; Carulli, Lucia; Dorval, Ganazzi; Carulli, Nicola; Loria, Paola
abstract
AIM: To evaluate carotid intima-media thickening (IMT)and plaques, gallstone disease (GD) and fatty liver (FL)as a function of age.METHODS: In 449 subjects, FL and carotid diseasewere assessed ultrasonographically. In a subgroup of65/449 patients with non-alcoholic fatty liver disease(NAFLD), carotid disease, GD and associated factorswere determined.RESULTS: FL of unspecifi ed etiology was more commonin younger and GD in older individuals. FL subjectshad an increased prevalence of IMT and a decreasedprevalence of plaques and manifested carotid diseaseearlier. Plaques were more common in subjects with GD.Age was an independent predictor of carotid diseaseoutcome and FL was a protective factor for plaques. InNAFLD, there was an inverse correlation between bodyweight and age and the latter independently predictedcarotid fi ndings.CONCLUSION: Cardiovascular risk in patients with FLand NAFLD needs to be assessed as a function of ageand body weight.
2006
- Hepatic nuclear receptors in human cholelithiasis: A link with insulin resistance?
[Abstract in Rivista]
Bertolotti, Marco; Gabbi, C; Anzivino, Claudia; Crestani, M; Mitro, N; del Puppo, M; Rossi, Aldo; Carulli, Lucia; Loria, Paola; Carulli, Nicola
abstract
Little is known on the molecular mechanisms underlying cholesterol cholelithiasis even if previous evidence has suggested that reduced production of bile acids might play a role. AIM of the present study was to analyze the hepatic expression of a number of genes involved in bile acid metabolism in human cholelithiasis. METHODS. Surgical liver biopsies were obtained in 11 patients with untreated cholesterol cholelithiasis and 9 gallstone-free subjects; mRNA levels of CYP7A1 and related nuclear receptors and coactivators were assayed by real-time quantitative RT-PCR. RESULTS. No differences were detected the expression of any of the genes studied, with the exception of PPAR-gamma coactivator 1 (PGC-1), a transcriptional coactivator of CYP7A1 involved in insulin sensitivity and energy balance, which was significantly (p < 0.01) less expressed in gallstone subjects. Expression of PGC-1 was linearly correlated with the bile acid receptor FXR in the population of gallstone patients (r = 0.87 on a log scale, p < 0.01). CONCLUSIONS. PGC-1 appears to play a role in the prevention of cholesterol gallstone disease in humans; the finding might suggest a link with insulin resistance conditions. This effect might take place via interaction with the bile acid receptor FXR, whose protective role in cholelithiasis has been suggested by recent evidence in animal models. PGC-1 and related genes might therefore represent molecular targets for the prevention and/or treatment of gallstone disease.
2006
- Influence of age on bile acid synthesis: Role of hepatic expression of nuclear receptors
[Abstract in Rivista]
C., Gabbi; Bertolotti, Marco; Anzivino, Claudia; D., Macchioni; M., Crestani*; N., Mitro*; M., Del Puppo**; Carulli, Lucia; Loria, Paola; Carulli, Nicola
abstract
Bile acid synthesis plays a key role in cholesterol homeostasis. Recent data have highlighted the role of nuclear receptors in the transcriptional regulation of the limiting enzyme, cholesterol 7alpha-hydroxylase (CYP7A1), in cellular and animal models. AIM of the present study was to analyze the effects of age on the expression of CYP7A1 and related nuclear receptors in human livers. METHODS. Liver biopsies were obtained in 22 untreated patients with abdominal diseases requiring surgery. mRNA levels of CYP7A1 and related nuclear receptors and coactivators were assayed by quantitative real-time RT-PCR. Serum levels of 7alpha-hydroxycholest-3-one (3-ONE), a marker of bile acid synthesis, were assayed by GC-MS. RESULTS. Aging was inversely correlated with serum 3-ONE and with CYP7A1 mRNA levels (r = -0.53 and r = -0.48, respectively, p < 0.05). Among the different nuclear factors, CYP7A1 mRNA best correlated with HNF-4 (r = 0.51, p < 0.05); HNF-4 levels were inversely correlated with age (r = -0.72, p < 0.05). Age was inversely correlated with serum IGF-1 levels which, in turn, were directly correlated with HNF-4 expression. CONCLUSIONS. Aging associates with reduced bile acid synthesis, in agreement with previous evidence from this laboratory; this might be related with reduced expression of hepatic nuclear receptors, in particular HNF-4, in turn leading to reduced expression of CYP7A1. Age-related modifications of the GH/IGF axis might play a role. The changes observed may help to understand age-related modifications of cholesterol metabolism.
2006
- MOLECULAR REGULATION OF STEROL METABOLISM BY BILE ACIDS IN CULTURED HUMAN HEPATOCYTES
[Abstract in Rivista]
Anzivino, Claudia; Bertolotti, Marco; C., Gabbi; M., Ricchi; Tagliafico, Enrico; Tenedini, Elena; Carulli, Lucia; Carubbi, Francesca; Loria, Paola; Carulli, Nicola
abstract
Disruption of hepatic cholesterol homeostasis may predispose to important clinical conditions such as cholelithiasis and atherosclerosis. The regulatory role of nuclear receptors has recently been underlined but the integration of the different metabolic pathways is largely unknown. AIM of the present study is to analyze the expression of a number of genes involved in cholesterol and bile acid metabolism in cultured human hepatocytes. METHODS. HepG2 cells were incubated with 100 micromol concentrations of different bile acids (DCA, CDCA, UDCA) for 24 hr. mRNA levels of cholesterol 7alpha-hydroxylase (CYP7A1), LDL-receptor, HMG-CoA reductase and a number of nuclear receptors and coactivators involved in sterol metabolism were assayed by real-time RT-PCR. RESULTS. A significant effect of bile acid treatment, detected by ANOVA, was shown on the expression of CYP7A1 and SHP, which were respectively reduced and increased by treatment with the hydrophobic bile acids DCA and CDCA, but not with UDCA; expression of SREBP-2 and LDL-receptor were also significantly increased by hydrophobic bile acids. CONCLUSIONS. Hydrophobic, but not hydrophilic bile acids suppress CYP7A1 expression, possibly via increased expression of SHP. Surprisingly, the same bile acids seem to enhance the expression of SREBP-2 and of genes involved in LDL uptake, mimicking a condition of cholesterol depletion. Knowledge of the subtle relationships linking bile acid and cholesterol metabolism might provide useful information for the management of cholesterol accumulation conditions.
2006
- Multidisciplinary approach to the treatment of metabolic and morphologic alterations of HIV-related lipodystrophy
[Articolo su rivista]
Guaraldi, Giovanni; G., Orlando; N., Squillace; DE SANTIS, Giorgio; A., Pedone; A., Spaggiari; D., De Fazio; Vandelli, Maria Angela; M., De Paola; C., Bertucelli; C., Aldrovandi; Nardini, Giulia; Beghetto, Barbara; V., Borghi; Bertolotti, Marco; Bagni, Bruno; M. G., Amorico; A., Roverato; Esposito, Roberto
abstract
Background: Treatment for metabolic and morphologic alterations in HIV-related lipodystrophy include medical therapy, physical exercise, and surgical interventions. Method: We assessed the efficacy and safety of a comprehensive multidisciplinary approach for treating morphological and metabolic alterations of the lipodystrophy syndrome in consecutive patients attending the Metabolic Clinic (MC) of the University of Modena and Reggio Emilia who had at least 2 evaluations over a 48-week period. 245 patients were evaluated: 143 (62.4%) were men, 74 (36.1%) presented with lipoatrophy, 10 (4.9%) with fat accumulation, 93 (45%) with mixed forms, 24 (11.3%) had hypercholesterolemia (LDL >1 60 mg/dL), 87 (38%) had hypertriglyceridemia (TG >1 50 mg/dL), 13 (5.7%) had diabetes (glucose >1 26 mg/ dL), and 78 (44%) had insulin resistance (HOMA-IR >4). Results: At follow-up, a significant improvement was observed in both objective and subjective variables. Anthropometric improvement was observed in waist to hip ratio, waist circumference, and right and left cheek dermal thickness measurements. A nonsignificant improvement was observed in fat and lean regional mass by DEXA; CT showed improvement in visceral and subcutaneous adipose tissue. Glucose, HOMA-IR, total cholesterol, and APO B improved. Subjective variables improved in aesthetic satisfaction. Conclusion: We conclude that the medical and surgical interventions proposed in this multidisciplinary therapeutic approach are efficacious and safe in the management of lipodystrophy.
2006
- Risk for cardiovascular events in a local population of diabetic patients
[Abstract in Rivista]
E., Pellegrini; M., Maurantonio; D'Amico, Roberto; B., Madeo*; I. M., Giannico; D., Ganazzi; A., Baldini*; Carulli, Lucia; Loria, Paola; Bertolotti, Marco; Carulli, Nicola
abstract
Diabetes mellitus (DM) is a major risk factor for cardiovascular (CV) events. Many algorithms have been devised to assess CV risk, some of which specific for diabetics. Most of them, however, are based on data which can hardly be extrapolated to Mediterranean countries. AIM of the present study was to analyze CV risk and the incidence of CV events in a local cohort of patients with type 2 DM. METHODS. Clinical charts of two Diabetes Clinics of Modena in the period 1991-1994 were analyzed. Patients aged 35-65 with type 2 DM and no history of CV disease were eligible. Global CV risk was computed according to Framingham, RISCARD, Progetto Cuore and UKPDS algorithms and compared with the actual rate of CV events over the following 10 years. RESULTS. 774 patients were screened; 473 of them (61.1%) were eligible on the basis of predefined criteria and completeness of data. In such population an absolute 10-yr risk rate of 10.8% was observed. When comparing the estimated risk rate according to the different functions, a high degree of variability was present; Italian algorithms were more consistent with the observed data even if only 31% of patients with CV events had a risk > 20% at initial observation. CONCLUSIONS. Estimation of CV risk is largely dependent on the algorithm adopted and on the baseline risk of the reference cohort. Functions designed for a specific population should be adopted. The overall performance of such functions is however low. The algorithm derived from the present study will be utilized for a prospective evaluation of CV risk in our local cohort.
2006
- Structure and concentartion of differenty fatty acid (FFAS) affect steatosis extent and apoptosis in hepatocytes coltures
[Abstract in Rivista]
Ricchi, M; Carulli, Lucia; Odoardi, Mr; Bormioli, Ml; Anzivino, Claudia; Lonardo, A; Bertolotti, Marco; Carulli, Nicola; Loria, Paola
abstract
Steatosis can be induced in hepatocytes coltures . FFAs strucutre , concentration and cell line type, arei mportant factors in modulating extent of TG storage and apoptosis. Oleic acid is more steatogenic but less toxic than palmitic and when associted to palmitic , decreases its toxicity.
2006
- Tenofovir treatment in HIV-related lipodystrophy syndrome. Retrospective observational forty-eight weeks follow-up study
[Articolo su rivista]
Guaraldi, Giovanni; Orlando, Gabriella; Roverato, A.; DE SANTIS, Giorgio; Pedone, A.; Spaggiari, A.; Baccarani, A.; De Fazio, D.; Vandelli, M.; Bertucelli, C.; Beghetto, Barbara; Nardini, Giulia; Borghi, V.; Grisendi, C.; Bertolotti, Marco; Carubbi, Francesca; Zini, I.; Esposito, Roberto
abstract
Efficacy and safety of morphological and metabolic alterations treatment in HIV related lipodystrophy syndrome have never been evaluated outside clinical trials and progression of lipodystrophy remains uncertain. This is a 48 weeks follow up observational retrospective study over consecutive patients attending the Metabolic Clinic of the University of Modena and Reggio Emilia in whom a biochemical, antropometric with DEXA and psychometric evaluation was available. The aim of this research was to assess efficacy and safety of switching to tenofovir (TDF) in the context of the multidisciplinary interventions offered in the Metabolic Clinic comprehensive of: dietary counseling, physical activities, surgical treatment for facial lipoatrophy or fat hypertrophy and psychological support. In a cohort of 189 people with lipodystrophy, TDF was part of the antiretroviral regimen in 125 individuals (82 males e 43 females). TDF-control group was made of 64 individuals (38 males e 26 females). The two study groups were homogeneous for metabolic, morphologic and psychometric profile at baseline. In the follow up period a significant improvement was observed in TDF+ group with regard of blood glucose, insuline, triglyceride. Non significant change in morphologic alterations evaluated with DEXA was observed in the two study groups. With regards of psychometric evaluations, a striking improvement was observed in aesthetic satisfaction of the face, of the body, of body image and depression. In the cohort, no progressions of HIV disease nor serious adverse events were observed. We conclude that switching to tenofovir in the context of the multidisciplinary interventions offered in the Metabolic Clinic is efficacious and safe in the management of LD
2005
- Gallstone disease in non-alcoholic fatty liver: Prevalence and associated factors
[Articolo su rivista]
P., Loria; A., Lonardo; S., Lombardini; Carulli, Lucia; A., Verrone; D., Ganazzi; A., Rudilosso; D'Amico, Roberto; Bertolotti, Marco; N., Carulli
abstract
Background: Insulin resistance is a risk factors for non-alcoholic fatty liver disease (NAFLD) and for gallstone disease (GD). Aims of the present study were to assess the prevalence of and factors associated with GD in unselected patients with NAFLD. Methods: A total of 161 consecutive patients with NAFLD diagnosed through compatible ultrasonography in the absence of known etiologies of liver disease (in all patients) and/or confirmed histologically (in 61 patients), was studied. Gallstone disease was diagnosed through ultrasound scanning or on the basis of previous cholecystectomy. Anthropometric and biochemical variables and concurrent diseases were compared in 32 NAFLD-GD patients and in 129 NAFLD patients without GD (controls) according to gender. Results: The overall prevalence of GD was 19.88%, higher in female patients (P< 0.05), who were older (P < 001). The overall percentage of GD increased with age (P < 0.05). The GD patients had higher uric acid (men), total cholesterol and apolipoprotein B (apo-B) serum concentrations (women, P < 0.05); women also had a higher prevalence of hypertriglyceridemia (P < 0.05). The age-corrected odds ratio of having GD by tertiles increased significantly with increasing uric acid (men) and with increasing total cholesterol, triglycerides and apo-B (women). At univariate continuous analysis GD was associated with insulin 120 min and uric acid in male patients; and with body mass index, insulin 120 min, apo-B, total cholesterol and triglycerides in female patients. On multivariate analysis it was found that among these factors only uric acid in men and apo-B in women were independently associated with GD in NAFLD. Conclusions: The prevalence of GD in NAFLD is more elevated than reported in the general population. The factors independently associated with GD in NAFLD are different from those reported in the general population and vary according to the gender.
2005
- Review article: hyperlipidaemia and cardiovascular risk
[Articolo su rivista]
Bertolotti, Marco; M., Maurantonio; C., Gabbi; Anzivino, Claudia; Carulli, Nicola
abstract
Hyperlipidaemia represents a determinant for the development of atherosclerosis and an important risk factor for cardiovascular disease, particularly in the context of the insulin resistance syndrome. This is characterized by alterations in the profile of plasma lipoprotein including high triglyceride levels, low high-density lipoprotein cholesterol concentrations and the appearance of qualitatively modified, small-dense low-density lipoproteins. Many charts and algorithms have been developed to estimate the entity of coronary and cardiovascular risk as related to dyslipidaemia, on the basis of additional individual risk factors and conditions: most include age and gender, smoking status, hypertension and diabetes. They should preferably be utilized in consistent patient populations, in terms of geographical areas and general risk profile. Pharmacological treatment of dyslipidaemia, in particular with statin drugs, was shown to greatly improve cardiovascular morbidity and mortality. A body of evidence also underlines the need for a multidisciplinary approach, integrating non-pharmacological lifestyle and diet interventions, as well as treatment of concomitant diseases (hypertension and diabetes).
2004
- Dislipidemie.In Teodori 2004. Trattato italiano di medicina interna
[Monografia/Trattato scientifico]
Carulli, Nicola; Carubbi, Francesca; Bertolotti, Marco
abstract
le dislipidemie. Fisiopatologia, diagnosi e terapia.
2004
- Genetic determinants of NAFLD. Role of PC-1, K121Q, IL-6 G 174C and MTO G 493T
[Abstract in Rivista]
Carulli, Lucia; Rondinella, S; Lombardinis, ; Canedi, I; Ricchi, M; Bertolotti, Marco; Carulli, Nicola; Loria, Paola
abstract
Study of the role of genetic polymorphism on determining fatty liver. In particular I eavaluated PC-1 K121Q, Il-6 G 174C and MTP G 493T in 100 healthy control and 123 Nafld subjectsOnly PC-1 K121Q, and Il-6 G 174C seem to associated with greater inflammatory activity and more advanced NAFLD.
2004
- HEPATIC NUCLEAR RECEPTOR EXPRESSION AND REGULATION OF BILE ACID SYNTHESIS IN HUMANS
[Abstract in Rivista]
Bertolotti, Marco; C., Gabbi; Anzivino, Claudia; M., Crestani; N., Mitro; M., Del Puppo; Carulli, Lucia; Rossi, Aldo; Loria, Paola; Carulli, Nicola
abstract
Bile acid synthesis plays a crucial role in cholesterol homeostasis. Recent evidence has highlighted the role of nuclear receptors in the regulation of the expression and activity of cholesterol 7alpha-hydroxylase (CYP7A1), the limiting enzyme, in cellular and animal models. Understanding the regulatory role of nuclear receptors in humans might help to define molecular targets for pharmacological intervention aimed to enhance hepatic cholesterol degradation. AIM of the present study was to analyze the expression of CYP7A1 and a number of related nuclear receptors in human liver. METHODS. Surgical liver biopsies were obtained in 40 patients; 30 of them were untreated, presenting gallbladder stones (12), non-metastatic abdominal cancer (10) or obstructive cholestasis (8); 10 subjects were receiving standard dose of CDCA (3), UDCA (5) or cholestyramine (2). mRNA levels of CYP7A1 and of the main nuclear receptors involved in its regulation (FXR, SHP, LRH-CPF-1, HNF-4, PGC-1) were assayed by real-time RT-PCR, using custom-designed primers and with sybr-green as an intercalator of double-stranded DNA. RESULTS. CYP7A1 mRNA showed a high degree of variability. No difference was detected between untreated gallstone and gallstone-free subjects regarding the expression of CYP7A1 and other genes, with the exception of PGC-1 which was significantly (p < 0.05 on a log scale) less expressed in gallstone subjects. In untreated, non-cholestatic subjects no correlation could be detected between CYP7A1 or other genes and age. Stepwise regression analysis of data from all non-cholestatic subjects, with CYP7A1 mRNA levels as the dependent variable, showed the strongest correlation with HNF-4 as the independent variable (r = 0.471 on a log scale, p < 0.05), all other genes (including SHP) bringing non-significant further contribution to the correlation. A very strong direct correlation (r = 0.880 on a log scale, p< 0.05) was detected between HNF-4 and LRH-CPF-1 expression. Finally, no difference was observed between cholestatic and non-cholestatic patients.CONCLUSIONS. Our data suggest that HNF-4 might play a relevant role in the regulation of CYP7A1 transcription in humans; on the other hand no evidence for a suppressive role of SHP, which was well documented in cellular models, was observed. As a whole, the interrelationships between the different nuclear receptors, and their physiological role, have still to be defined. Data on CYP7A1 expression support the view that post-transcriptional, and possibly post-translational levels of regulation may also play a critical role in the control of bile acid synthesis.
2004
- Non alcoholic Fatty liver disease ( NAFLD): and insulin reistance:does PC-1 K121Q play a role?
[Abstract in Rivista]
Carulli, Lucia; Canedi, I; Rondinella, S; Lombardini, S; Verrone, Am; Ricchi, M.; Lonardo, A; Bertolotti, Marco; Carulli, Nicola; Loria, Paola
abstract
NAFLD often associates with metabolic syndrome features. The polymorphism PC-1 K121Q associates with insulin resistance.Does PC-1 K121Q associates with Nafld? Our data , indicate that PC-1K121Q is not required to develop NAFLD but it associates with higher extent of steatosis and greater inflammatory activity, possibly as a result of insulinresiatnce.
2004
- non alcoholic fatty liver disease ( NAFLD) :is femlae sex safer?
[Abstract in Rivista]
Carulli, Lucia; Lombardini, S; Lonardo, A; Leonardi, F; Bertolotti, Marco; Ricchi, M; Verrone, A; Bagni, A; Carulli, Nicola; Loria, Paola
abstract
Women are less suceptible to liver disease and fibrosis progression si lower. In our NAFLD population females were older and with higher prevaelnce of meatbolic disorder compared to maels. But the majority of them had mild histological NAFLD. These data suggets that female hormones might delay teh appearance of nafld and its progression to fibrosis.
2003
- Epatopatia steatosica non alcolica:definizione e aspetti clinici.
[Articolo su rivista]
Carulli, N; Bagni, A; Carulli, Lucia; Borsatti, A; Bertolotti, Marco; Loria, P.
abstract
Non alcoholic fatty liver disease (NAFLD) is an acohol-like liver diseasethat develops in subjects with none or negligible alcohol intake.pathological features range from simple hepatic steatosis at one end to cirrhosis at teh opposite extreme of teh spectrum . NAFLd is trongly associated with obesity, type 2 diabetes, hyperlipidemia and may be considered as afeature of the metabolic syndrome.NAFLD may be secondary to malnutrition, genetic defects, drugs and enviromental toxic compuonds. Most of the subjects with NAFLD are asyntomatic. Laboraory features may show raised alanine aminotransferase>aspartate amin otransferase. Ultrasonography shows hyperechogenig liver parenchyma.Signs and symptoms follow the progression of the disease and are those of decompensated liver disease.
2003
- Influence of newly synthesized cholesterol on bile acid synthesis during chronic inhibition of bile acid absorption
[Articolo su rivista]
Bertolotti, Marco; L., Zambianchi; Carulli, Lucia; Ms, Simonini; M., Del Puppo; Mg, Kienle; P., Loria; A., Pinetti; N., Carulli
abstract
The effects of newly synthesized cholesterol availability on bile acid synthesis are largely unknown, particularly in humans. The present study was aimed to study the changes induced on bile acid synthesis by simvastatin, a competitive inhibitor of hydroxymethyl glutaryl-CoA (HMG-CoA) reductase, the rate-limiting enzyme of cholesterol synthesis, during pharmacologic interruption of the enterohepatic circulation. Six patients with primary hypercholesterolemia were studied in basal conditions, after treatment with the bile acid binding resin cholestyramine alone (8-16 g/d for 6-8 weeks) and subsequently in combination with simvastatin (40 mg/d for 6-8 weeks). Cholesterol 7alpha-hydroxylation rate, a measure of total bile acid synthesis, was assayed in vivo by tritium release analysis. Serum lathosterol levels were assayed by gas chromatography mass spectrometry as a measure of cholesterol synthesis. Serum total and low-density lipoprotein-cholesterol were reduced significantly after cholestyramine (by 26% and 30%, respectively) and during combined treatment (by 47% and 55%). 7alpha-Hydroxylation rates increased nearly 4-fold with cholestyramine alone; addition of simvastatin induced a significant decrease of hydroxylation rates (cholestyramine alone, 1,591 +/- 183 mg/d; plus simvastatin, 1,098 +/- 232 mg/d; mean +/- SEM; P <.05). Hydroxylation rates significantly correlated with serum lathosterol/ cholesterol ratio (r = 0.79, P <.05). In conclusion, in conditions of chronic stimulation bile acid synthesis may be affected by changes in newly synthesized cholesterol availability. The finding might relate to the degree of substrate saturation of microsomal cholesterol 7alpha-hydroxylase; alternatively, newly synthesized cholesterol might induce a stimulatory effect on cholesterol 7alpha-hydroxylase transcription.
2003
- La clinica metabolica per il trattamento della lipodistrofia
[Abstract in Rivista]
Guaraldi, Giovanni; Orlando, G.; DE SANTIS, Giorgio; De fazio, D.; Giuricin, F.; Vandeli, M.; Bertolotti, Marco; Galetti, G.; Sartini, S.; Murri, R.; Covezzi, R.; Esposito, Roberto; Wu, A.
abstract
La presa in carico del paziente con lipodistrofia trascende le competenze infettivologiche e necessita di una rete di specialisti competenti per la diagnosi, il monitoraggio, e il trattamento delle alterazioni metaboliche e morfologiche ad essa associate. L'obiettivo della ricerca è di illustrare la metodologia di lavoro e i risultati di questo approccio multidisciplinare integrato denominato "Clinica Metabolica"
2003
- Non-organ-specific autoantibodies in nonalcoholic fatty liver disease: Prevalence and correlates
[Articolo su rivista]
Loria, Paola; A., Lonardo; F., Leonardi; C., Fontana; Carulli, Lucia; Am, Verrone; A., Borsatti; Bertolotti, Marco; F., Cassani; A., Bagni; P., Muratori; D., Ganazzi; Fb, Bianchi; N., Carulli
abstract
Eighty-four consecutive subjects with nonalcoholic fatty liver disease (NAFLD) were tested for non-organ-specific autoantibodies (NOSA) by indirect immunoflorescence. Indices of insulin resistance and biochemical and anthropometric parameters were assessed. The overall prevalence of anti-nuclear-antibodies (ANA), smooth muscle antibodies (SMA) and anti-mitochondrial-antibodies (AMA) was 35.7% (30/84), 18 subjects (21.4%) being positive for ANA, 4 (4.7%) for SMA, 6 for ANA and SMA, and 2 for AMA. NOSA-positive subjects were older (P < 0.01) and mostly females (63.3%). No significant difference was found in the age-corrected parameters studied, except for copper and ceruloplasmin, which was more elevated in NOSA-positive patients. The subset of high titer (&GE;1:100) ANA-positive patients had significantly (P < 0.05) greater insulin resistance than ANA-negative patients. In contrast, SMA-positive patients had higher gammaglobulin and significantly lower insulin resistance as compared to high-titer ANA-positive patients. In 3 NOSA-positive but not in NOSA-negative patients, liver biopsy disclosed features of overlapping NASH with autoimmune hepatitis, partially responding to diet combined with steroid treatment. In conclusion, NOSA positivity in NAFLD is more prevalent than in the general population. High-titre ANA but not SMA positivity is associated with insulin resistance.
2002
- Comparative cytotoxic and cytoprotective effects of taurohyodeoxycholic acid (THDCA) and tauroursodeoxycholic acid (TUDCA) in HepG2 cell line.
[Articolo su rivista]
Carubbi, Francesca; Me, Guicciardi; M., Concari; Loria, Paola; Bertolotti, Marco; Carulli, Nicola
abstract
This study was performed to compare the effects of two hydrophilic bile acids, taurohyodeoxycholic acid (THDCA) and tauroursodeoxycholic acid (TUDCA), on HepG2 cells. Cytotoxicity was evaluated at different times of exposure by incubating cells with increasing concentrations (50-800 micromol/l) of either bile acid, while their cytoprotective effect was tested in comparison with deoxycholic acid (DCA) (350 micromol/l and 750 micromol/l)-induced cytotoxicity. Culture media, harvested at the end of each incubation period, were analyzed to evaluate aspartate transaminase (AST), alanine transaminase and gamma-glutamyltranspeptidase release. In addition, the hemolytic effect of THDCA and TUDCA on human red blood cells was also determined. At 24 h of incubation neither THDCA nor TUDCA was cytotoxic at concentrations up to 200 and 400 micromol/l. At 800 micromol/l both THDCA and TUDCA induced a slight increase in AST release. At this concentration and with time of exposure prolonged up to 72 h, THDCA and TUDCA induced a progressive increase of AST release significantly (P<0.05) higher than that of controls being AST values for THDCA (2.97+/-0.88 time control value (tcv) at 48 h and 4.50+/-1.13 tcv at 72 h) significantly greater than those of TUDCA (1.50+/-0.20 tcv at 48 h and 1.80+/-0.43 tcv at 72 h) (P<0.01). In cytoprotection experiments, the addition of 50 micromol/l THDCA decreased only slightly (-5%) AST release induced by 350 micromol/l DCA, while the addition of 50 micromol/l TUDCA was significantly effective (-23%; P<0.05). Higher doses of THDCA or TUDCA did not reduce toxicity induced by 350 micromol/l DCA, but were much less toxic than an equimolar dose of DCA alone. At the concentration used in this experimental model neither THDCA nor TUDCA was hemolytic; however at a very high concentration (6 mmol/l) both bile acids induced 5-8% hemolysis. We conclude that bile acid molecules with a similar degree of hydrophilicity may show different cytotoxic and cytoprotective prope
2002
- Fasting insulin and uric acid levels but not indices of iron metabolism are independent predictors of non-alcoholic fatty liver disease. A case-control study
[Articolo su rivista]
A., Lonardo; Loria, Paola; F., Leonardi; A., Borsatti; P., Neri; M., Pulvirenti; Am, Verrone; A., Bagni; Bertolotti, Marco; Ganazzi, Dorval; Carulli, Nicola
abstract
Background. Non-alcoholic fatty liver disease is a common reason for hepatological consultation and may herald severe hepatic and extra-hepatic disease. The aetiopathogenesis of this condition is an area of increasing interest. Aim. To evaluate anthropometric and biochemical factors associated to non-alcoholic fatty liver disease in a case-control study. Methods. Demographic and biochemical data of 60 consecutive patients with bright liver absent-to-low alcohol consumption, no evidence of viral, genetic and autoimmune diseases, were compared to those of 60ED age- and gender-matched historical controls without fatty liver by univariate and multiple logistic regression analysis. Results. Patients were more often hypertriglyceridaemic, obese and diabetic than controls (p<01). Mean values of alanine transaminase, gammaglutamyltranspeptidase, triglycerides, uric acid, fasting and log insulin, transferrin percent saturation and ferritin were significantly higher in the patients, while transferrin and quantitative insulin sensitivity check index, a quantitative insulin sensitivity index, were lower No iron storage was found in those who underwent liver biopsy. At univariate analysis the relative risk for non-alcoholic fatty liver disease significantly increased (p<0.05) with increasing body mass index, fasting insulin, alanine transaminase, uric acid, triglycerides and gammaglutamyltranspeptidase; it decreased with increasing transferrin and quantitative insulin sensitivity check index. Multiple logistic regression analysis disclosed only fasting insulin and uric acid to be independent predictors of non-alcoholic fatty liver disease (p<0.05). Conclusions. Fasting insulin and serum uric acid levels indicating Insulin resistance, but not indices of iron overload, are independent predictors of non-alcoholic fatty liver disease.
2002
- determinants of lt levels and fibrosis in non alcoholic fatty liver disease
[Abstract in Rivista]
Loria, P; Lonardo, A; D'Amico, Roberto; Leonardi, F; Borsatii, A; Verrone, A; Carulli, Lucia; Rudilosso, A; Ricchi, M; Bertolotti, Marco; Ganazzi, D. Carulli N.
abstract
The study suggets that as yet incomplety understood factors might account for the progression from steatosis to steatohepatitis and that predictors of fibrosis in our unselected population with non alcoholic fatty liver disease are differet compared to other studies.
2002
- regulation of bile acid synthesis in humans: availability of newly sythetized cholesterol is a limiting fator during pharmacological inhibition of bile acid recirculation.
[Abstract in Rivista]
Bertolotti, Marco; Zambianchi, L; Carulli, Lucia; Loria, Paola; Simonini, Ms; Carulli, Nicola
abstract
In conditions of chronically stimulated bile acid syntehsis , obtained by pharmacological interruption of bile acid recirculation, inhibition of HMGCoA-reductase induces a relative reduction of Bile Acids synthesis rates. These data suggets taht newly synthesized cholestreol avilabuility maybe a limiting factor for bile acid synthesis under these conditions as previously observed in bile fistula patients.These findings indirectly suggedt a feedforward stimulation exerted by intracellular newly synthesized choletsreol on bile acids synthesis which might involve nuclear receptor and/or coactivators of 7 alpha hydroxylase transcription.
2001
- Inhibition of intestinal cholesterol absorption by surfomer [alpha-olefin maleic acid] affects hepatic cholesterol synthesis and low density lipoprotein transport in hamsters fed a fat-enriched diet
[Articolo su rivista]
Bertolotti, Marco; Dk, Spady
abstract
Background, Surfomer (alpha -olefin maleic acid) reduces intestinal cholesterol absorption. Aims. This study was performed to investigate the effect of surfomer on cholesterol synthesis and low density lipoprotein in hamsters fed a hypercholesterolaemic, lipid-enriched diet. Animals and methods. Male hamsters were fed a diet enriched in cholesterol (0.07%) and saturated fatty acids (coconut oil 20%); the diet was supplemented with 3% surfomer: for 1-4 weeks. Cholesterol synthesis was assessed measuring incorporation of [H-3]water into tissue sterols; low density lipoprotein clearance was determined using a primed-continuous infusion of [I-125]tyramine-cellobiose lipoprotein. Results. Cholesterol synthesis was suppressed after 3 weeks of hyperlipidaemic diet in liver and small bowel (by 88% and 38%, respectively) and was significantly increased by supplementing the fat-enriched diet with surfomer. Low density lipoprotein-cholesterol was increased by 44% after 4 weeks of hyperlipidaemic diet, in parallel with a decrease in hepatic low density lipoprotein clearance rates (48 +/-3 vs 68 +/-7 mul of plasma/h per g of tissue). Concurrent treatment with surfomer for 1, P or 4 weeks prevented the decrease of clearance and maintained normal low density lipoprotein-cholesterol levels at all time points, Conclusions. Surfomer represents a powerful tool to investigate the impact of cholesterol absorption on sterol homeostasis. Furthermore, since surfomer appears to normalize low density lipoprotein transport in hamsters fed a diet comparable to a lipid-rich western-style regimen, this drug may deserve consideration as an adjunct treatment for hypercholesterolaemia in selected patient groups.
2001
- Suppression of bile acid synthesis, but not of hepatic cholesterol 7alpha-hydroxylase expression, by obstructive cholestasis in humans
[Articolo su rivista]
Bertolotti, Marco; Carulli, Lucia; Concari, M; Martella, P; Loria, Paola; Tagliafico, Enrico; Ferrari, S; Del Puppo, M; Amati, B; De Fabiani, E; Crestani, M; Amorotti, Claudio; Manenti, A; Carubbi, Francesca; Pinetti, A; Carulli, N.
abstract
Regulation of bile acid synthesis, a key determinant of cholesterol homeostasis, is still incompletely understood. To elucidate the feedback control exerted on bile acid biosynthesis in humans with obstructive cholestasis, 16 patients with bile duct obstruction were studied. In vivo 7alpha-hydroxylation, reflecting bile acid synthesis, was assayed in 13 of them by tritium release analysis. Serum 27-hydroxycholesterol was determined by gas chromatography-mass spectrometry. In a subgroup, hepatic cholesterol 7alpha-hydroxylase mRNA was assayed by real-time polymerase chain reaction (PCR), enzyme activity was determined by isotope incorporation, and microsomal cholesterol content was assayed by gas chromatography-mass spectrometry. Age-matched control subjects were studied in parallel. Hydroxylation rates were lower in cholestatic patients (108 +/- 33 mg of cholesterol per day, mean +/- SEM; controls: 297 +/- 40 mg/d; P <.01). The reduction was proportional to the severity of cholestasis, and synthetic rates were normalized in 4 subjects restudied after resolution of biliary obstruction. Consistent findings were obtained by analysis of serum 7alpha-hydroxycholesterol levels. On the other hand, hepatic cholesterol 7alpha-hydroxylase mRNA, microsomal enzyme activity, and cholesterol content tended to be increased in cholestasis. Finally, serum 27-hydroxycholesterol levels were slightly reduced in cholestatic subjects and were not related with the severity of the disease. Suppression of in vivo bile acid synthesis with no corresponding reduction in tissue 7alpha-hydroxylase expression and activity is consistent with nontranscriptional, posttranslational levels of regulation; these may play a role in the feedback control of bile acid synthesis in particular conditions. Alteration of the alternate biosynthetic pathway seems unlikely according to the present data.
2000
- Bleeding jejunal varices and portal thrombosis in a splenectomized patient with hereditary spherocytosis
[Articolo su rivista]
Bertolotti, Marco; Loria, P; Martella, P; Carulli, Lucia; De Santis, M; Carulli, N.
abstract
Bleeding from varices located in the small bowel is a
very uncommon finding; nonetheless, such events accompany
with a high mortality rate (1– 4). Moreover,
early diagnosis of jejunal or ileal varices cannot usually
be accomplished with standard diagnostic tools
(ie, esophagogastroduodenoscopy, colonoscopy).
Most reports in the literature relate to subjects with
liver cirrhosis, often with hepatocarcinoma; in unusual
anatomical situations, varices may develop beyond
the ligament of Treitz in adjunct to the far more
common location in the esophageal and gastric wall.
Thrombosis of the portal vein is a common feature in
such conditions. Portal thrombosis has also been described
in association with overt or latent myeloproliferative
diseases (5); its occurrence in nonneoplastic
hematological conditions in subjects with normal liver
function is quite uncommon.
This report describes the observation of jejunal
varices, with repeated episodes of “melena of unknown
origin,” some of which quite severe, as their
clinical presentation in a patient with portal thrombosis
and with otherwise absolutely normal liver function,
who had undergone splenectomy for hereditary
spherocytosis in early adolescence.
2000
- Nuove prospettive terapeutiche con acidi biliari.
[Capitolo/Saggio]
Carulli, Nicola; Loria, Paola; Carubbi, Francesca; Bertolotti, Marco; Concari, M.
abstract
Eds. Paolo Gentilini, Editore Scientific Press
2000
- Review article: effect of bile salt pool composition on hepatic and biliary functions
[Articolo su rivista]
Carulli, N; Bertolotti, Marco; Carubbi, Francesca; Concari, M; Martella, P; Carulli, Lucia; Loria, P.
abstract
The enterohepatic recirculation of bile salts exerts important regulatory effects on many hepatic, biliary and intestinal functions: such regulation is likely to depend, to a large extent, on the physical-chemical property of hydrophobicity of the recirculating pool. The present review summarizes the main experimental evidence carried out by our research group over the past two decades, in the attempt to investigate systematically the relationships between structural properties and biological effects of bile acids in humans. Hydrophobic bile acids (chenodeoxycholic acid, deoxycholic acid), but not hydrophilic acids (ursodeoxycholic acid), significantly suppressed hepatic activity of HMG-CoA reductase, the limiting step of cholesterol synthesis, and in vivo cholesterol 7alpha-hydroxylation, the limiting step of bile acid synthesis. The output of biliary cholesterol and phospholipid was also directly related to the hydrophobicity of the bile acid pool. Finally, treatment with chenodeoxycholic acid, but not with ursodeoxycholic acid, significantly decreased gall-bladder emptying rates. When turning to the in vitro model of HepG2 cells, hydrophobic bile acids were found to induce greater cytotoxic and pro-apoptotic effects. From this series of studies, we conclude that the regulatory effects of bile acids on the liver and biliary tract are largely dependent on the hydrophobic-hydrophilic balance of the recirculating bile acid pool.
2000
- Suprression of in vivo bile acid synthesis, but not of in vitro cholesterol 7 alpha-hydroxylase expression, by biliary obstruction in humans
[Articolo su rivista]
Bertolotti, Marco; Carulli, Lucia; Concari, M; Martella, P; Loria, Paola; Tagliafico, Enrico; De Fabiani, E; Amorotti, Claudio; Carulli, Nicola
abstract
1999
- Inquadramento delle sindromi colestatiche.
[Capitolo/Saggio]
N., Carulli; Bertolotti, Marco; Carubbi, Francesca; P., Loria
abstract
le sindromi colestatiche nell'uomo: inquadramento nosologico, etiopatogenesi e terapia
1999
- LA SECREZIONE LIPIDICA BILIARE
[Capitolo/Saggio]
P., Loria; Bertolotti, Marco; Carubbi, Francesca; P., Martella; M., Concari; N. C. A. R. U. L. L. I., Masson; Milano, P. P.
abstract
biliary lipid sceretion in humans: pathophysiology
1999
- Regolazione della sintesi di colesterolo e acidi biliari
[Capitolo/Saggio]
Bertolotti, Marco; M., Concari; Carulli, Lucia; Loria, Paola; P., Martella; Carulli, Nicola
abstract
La sintesi di colesterolo e di acidi biliari rappresentano tappe fondamentali nella regolazione dell'omeostasi di colesterolo nell'uomo. Molti aspetti della regolazione molecolare di queste vie metaboliche sono stati chiariti nelle ultime decadi, sottolineando il ruolo dei recettori nucleari nel controllo trascrizionale degli enzimi limitanti. Queste conoscenze possono avere importanti ricadute speculative ed applicative nell'uomo.
1999
- Ursodeoxycholic acid improves liver tests in chronic hepatitis - Results of a randomised controlled trial
[Articolo su rivista]
Bertolotti, Marco; AM Morselli, Labate; Ag, Rusticali; Loria, Paola; Carulli, Nicola
abstract
Objective: The present study was designed to investigate the effect of ursodeoxycholic acid (UDCA), a drug widely utilised in the management of cholestatic conditions, on liver function tests and symptom relief in a group of patients with chronic hepatitis of different aetiologies. Patients and Design: 219 patients (128 males, 91 females) with a histological diagnosis of chronic hepatitis were enrolled in a multicentre randomised trial with UDCA (300mg twice daily orally) and folic acid as a placebo. Treatment was carried out for 6 months. Biochemical markers of liver disease activity and scores for dyspeptic and systemic symptoms were determined. 213 patients completed the study (112 in the UDCA group, 101 in the placebo group). Results: UDCA induced a significant decrease (p < 0.001) in serum ALT, AST and gamma-GT; folic acid induced a significant reduction (p < 0.05) of ALT at 4 and 6 months of treatment, and of AST at 6 months. As assessed by ANCOVA, the changes in enzyme levels were significantly (p < 0.001) more pronounced in the UDCA group compared with placebo. This was accompanied by a significantly higher (p < 0.05) percentage of patients showing normalisation of liver enzymes. Analysis of the interference of pre-existing factors on the biochemical outcome showed a more marked effect of UDCA in reducing ALT in patients with elevated gamma-GT. Finally, the frequency and score of most symptoms were significantly reduced (p < 0.05) with ursodeoxycholic acid. Conclusions: The effectiveness and tolerability of ursodeoxycholic acid make it worth consideration as a useful therapeutic tool in the treatment of chronic hepatitis.
1998
- Influence of age and sex on serum concentrations of total dimeric activin A
[Articolo su rivista]
Loria, Paola; F., Petraglia; M., Concari; Bertolotti, Marco; P., Martella; S., Luisi; C., Grisolia; C., Foresta; Volpe, Annibale; A. R., Genazzani; Carulli, Nicola
abstract
Several studies have shown that activin A is secreted in substantial amounts into the systemic circulation. The changes that occur during menstrual cycle and pregnancy suggest a correlation with reproductive function. At present, however, no definitive evidence has confirmed this pattern throughout adult life; moreover, neither the origin nor the physiological implications of this circulating growth factor have been clearly defined. The aim of the present study was to evaluate whether circulating concentrations of activin A change in adult men and women according to age and sex, and to examine the possible correlation with serum concentrations of FSH. Total dimeric activin A was measured using a specific two-site enzyme immunoassay in serum specimens collected from a cohort of normal individuals enrolled in an epidemiological survey A group of men (n = 106) and one of women (n = 151) were subdivided into six age groups (20-30, 30-40, 40-50, 50-60, 60-70 and 70-90 years). In a small group of 8 men and 11 women, serum concentrations of activin A were evaluated twice, in specimens collected at an interval of 10 years. Serum FSH concentrations were also measured in all specimens. Serum concentrations of activin A were not significantly different in men and women and showed an age-related progressive increase between 20 and 50 pars of age (P < 0.01, those aged 40-50 compared with those aged 20-30 years). After the age of 50 years, activin A concentrations remained in the same range of values in women, whereas they increased significantly in men, reaching peak values between 70 and 90 years (P < 0.01 compared with the group aged between 20 and 50 years). From the age of 50 years, activin ii concentrations were significantly greater in men compared with those in women in the corresponding age groups (P < 0.001), Activin A concentrations correlated with age in men, but not in women, No significant correlation between concentrations of activin A and FSH was found in either sex. Activin A concentrations in specimens collected 10 years apart showed an increase in seven of eight men, but not in women. Finally, no significant variations of activin A concentrations were observed when fertile and postmenopausal women were compared. The present data indicate that circulating concentrations of activin A vary according to age; furthermore, men older than 50:years have greater concentrations than women. These changes, which occur irrespectively of FSH concentrations, indicate that circulating activin A is not a hormone of the reproductive axis.
1998
- Serum time course of naltrexone and 6 beta-naltrexol levels during long term treatment in drug addicts
[Articolo su rivista]
Ferrari, Anna; Bertolotti, Marco; A., Dell'Utri; U., Avico; Sternieri, Emilio
abstract
The pharmacokinetics of naltrexone have been scarcely explored in patients during chronic treatment despite the observation that the pharmacological effect of the drug is related to its plasma concentrations. In this study we investigated the time course of serum levels of naltrexone and its active metabolite, 6 beta-naltrexol, in 13 heroin addicts (3 F, 10 M; age 22-32 years) in the 24 h after 100 mg of naltrexone orally. Six patients were studied once, at different times during chronic treatment, whereas in seven patients the study was done at the beginning and after 1 month of naltrexone treatment. Four of these patients also repeated the study after 3 months of naltrexone treatment. Serum naltrexone and 6 beta-naltrexol were assayed by GLC with a nitrogen-phosphorus detector, Our results showed large differences among patients in serum naltrexone and 6 beta-naltrexol levels. On the other hand, there were no differences in serum time course of both substances in the same patient over 3 months. Peak levels and AUCs of naltrexone were lower than those of 6 beta-naltrexol in ten addicts and higher than those of the metabolite in three patients. No significant differences in the apparent half-lives of the two drugs were detected among groups. These data are consistent with the occurrence of a decreased first-pass metabolism of naltrexone in three patients leading to a larger availability of an oral dose. The increased bioavailability of the drug is not very important for opioid receptor antagonist activity but may play a role in naltrexone treatment safety. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.
1997
- Analgesic drug taking: Beliefs and behavior among headache patients
[Articolo su rivista]
Ferrari, Anna; Stefani, M; Sternieri, S; Bertolotti, Marco; Sternieri, Emilio
abstract
Objective.-To explore beliefs and behavior with respect to analgesic drug taking in headache patients. To compare episodic headache to chronic headache sufferers. Methods.-A consecutive series of 280 headache patients, newly admitted to the Headache Center of the University of Modena, all referred by their general practitioner, were asked to fill out a brief questionnaire, specially compiled for this survey. The questionnaire invited patients to indicate how they themselves thought they should best cope with their headache, and how they actually did so in practice. Results.-The majority of our patients had a positive attitude towards over-the-counter analgesics, which they believed to be more adequate than prescription drugs for acute treatment of their headache. They handled analgesics very carefully, believing it correct to take the drug only when the pain became unbearable, if it was not possible for them to stop work. Chronic headache patients tended to consume more prescription drugs than episodic headache sufferers. Furthermore, the majority of chronic sufferers, as opposed to episodic sufferers, took the analgesic even when not at work. Conclusions.-The use of over-the-counter drugs is considered the best way to treat acute headache even by subjects suffering from severe idiopathic headache and seeking professional care in specialized clinics. Prescribed analgesics are underused by patients with serious episodic headache, which is precisely the group for which they are principally intended.
1997
- Cholecystokinin increases bile acid synthesis with fetal parenteral nutrition but does not prevent stone formation
[Articolo su rivista]
Lg, Dawes; Jp, Muldoon; Ma, Greiner; Bertolotti, Marco
abstract
Total parenteral nutrition (TPN) is associated with cholestasis and gallstones. Gallbladder stasis may be important in the development of gallstones, and cholecystokinin (CCK) to stimulate gallbadder contraction has been proposed as a treatment to prevent this complication. We studied in vivo bile acid synthesis and bile acid output in miniswine on TPN to test whether daily CCK improves bile acid output and normalizes bile acid profiles with TPN. Nine miniswine were nutritionally maintained with TPN for 4 weeks; four pigs received CCK (0.1 mg/kg) iv daily. In vivo bile acid synthesis was measured with injection of 7 alpha-tritiated cholesterol. An increase in tritiated water reflects the activity of 7 alpha-hydroxylation, the rate-limiting step in bile acid synthesis. At the end of 4 weeks, bile was collected and bile acid output and bile salt profiles were determined. One of five animals on TPN developed gallstones while two of four receiving daily CCK developed stones. In vivo bile acid synthesis decreased with TPN (controls, 63 +/- 9 mg/24 hr versus TPN, 13 +/- 4 mg/24 hr) and increased in TPN animals with CCK treatment (TPN-CCK, 105 +/- 35 mg/24 hr). Bile acid profiles are changed with TPN with more secondary bile acids, this was not improved with CCK. CCK improved bile acid synthesis and bile acid output but failed to prevent gallstone formation or normalize bile salt profiles. In addition to promoting gallbladder contraction, CCK may have a stimulatory effect on bile acid synthesis. CCK alone did not prevent gallstone formation.
1997
- Effect of liver cirrhosis on the systemic availability of naltrexone in humans
[Articolo su rivista]
Bertolotti, Marco; Ferrari, Anna; Vitale, Giovanni; Stefani, M; Trenti, T; Loria, Paola; Carubbi, Francesca; Carulli, Nicola; Sternieri, Emilio
abstract
Naltrexone is a competitive opiate antagonist with high hepatic extraction. It is used for detoxification treatment for heroin addicts and has been proposed as a possible treatment of pruritus in cholestasis. Such patients are likely to have impaired liver function, underscoring the need to understand the pharmacokinetic behavior of naltrexone in liver disease. These studies were undertaken to evaluate the effect of liver cirrhosis on the plasma time-course of naltrexone.
METHODS: A total of 18 patients were investigated: seven migraine patients with normal liver function regarded as controls and 11 patients with liver cirrhosis (six with decompensated disease and five with preserved liver function). A bolus of 100 mg of naltrexone was administered orally in the morning, after an overnight fast. Blood samples were taken in basal conditions and at fixed intervals, up to 24 h after administration. Serum levels of naltrexone and of its major active metabolite, 6 beta-naltrexol, were assayed by reversed-phase HPLC analysis.
RESULTS: In control subjects, circulating concentrations of naltrexone were always much lower than those of 6 beta-naltrexol (area under the curve: naltrexone, 200 +/- 97 ng/ml x 24 h; 6 beta-naltrexol, 2467 +/- 730 ng/ml x 24 h, p < 0.01). In severe cirrhosis serum levels of 6 beta-naltrexol increased more slowly, so that circulating levels of naltrexone during the first 2-4 h after drug intake were higher than those of 6 beta-naltrexol (6 beta-naltrexol/naltrexone ratio at 2 h: controls, 10.91 +/- 4.80; cirrhosis, 0.39 +/- 0.18, p < 0.01). The area under the curve for naltrexone (1610 +/- 629 ng/ml x 24 h) was significantly greater than in controls, whereas that for 6 beta-naltrexol (2021 +/- 955 ng/ml x 24 h) was not significantly different. Patients with compensated cirrhosis showed an intermediate pattern. No differences in elimination half-life of the two drugs were detected among the groups.
CONCLUSIONS: Our data suggest the occurrence of important changes in the systemic availability of naltrexone and 6 beta-naltrexol in liver cirrhosis; such alterations are consistent with lesser reduction of naltrexone to 6 beta-naltrexol and appear to be related to the severity of liver disease. This must be considered when administering naltrexone in conditions of liver insufficiency.
1997
- Effect of taurohyodeoxycholic acid on biliary lipid secretion in humans
[Articolo su rivista]
Loria, Paola; M., Bozzoli; M., Concari; M. E., Guicciardi; Carubbi, Francesca; Bertolotti, Marco; D., Piani; A., Nistri; M., Angelico; M., Romani; Carulli, Nicola
abstract
This study aimed to determine the effect in humans of taurohyodeoxycholic acid, a 6 alpha-hydroxylated bile acid with hydrophilic properties, on bile lipid secretion, Four cholecystectomized patients who had gallstones and an interrupted enterohepatic circulation were intraduodenally infused with taurohyodeoxycholic and tauroursodeoxycholic acids on separate occasions at a dose of 0.8 to 1 g/h for 3 hours, In hourly bile samples collected for 8 hours after the beginning of the infusion, biliary bile acid composition (by high-performance liquid chromatography), biliary lipid concentrations (by standard methods), and distribution of biliary carriers (by gel chromatography) were evaluated, Blood liver function tests were performed before and after the infusions. Taurohyodeoxycholic and tauroursodeoxycholic acids became the predominant biliary bile acids in all patients except for one infused with taurohyodeoxycholic acid. Taurohyodeoxycholic acid stimulated significantly greater (P<.05) cholesterol and phospholipid secretion per unit of secreted bile acid (0.098 and 0.451 mu mol/mu mol, respectively) compared with tauroursodeoxycholic acid (0.061 mu mol/mu mol for cholesterol and 0.275 mu mol/mu mol for phospholipids). The secretory ratio between phospholipid and cholesterol was significantly higher after infusion of taurohyodeoxycholic acid (3.88 mu mol/mu mol) compared with taroursodeoxycholic acid (3.09 mu mol/pmol) (P<.05). Biliary enrichment with taurohyodeoxycholic acid was positively related with percent concentration of phospholipids but not with that of cholesterol, The opposite trend was observed in tauroursodeoxycholic acid-enriched biles. In both tauroursodeoxycholic acid- and tauroursodeoxycholic acid-rich bile, 80% to 90% of cholesterol was carried in a gel-chromatographic fraction corresponding to an apparent molecular weight of 80 to 200 kd. No alteration in liver function test results was observed after taurohyodeoxycholic acid infusion, In conclusion, taurohyodeoxycholic acid stimulates greater cholesterol and phospholipid secretion than tauroursodeoxycholic acid, but with a higher phospholipid/cholesterol secretory ratio. In bile enriched with both bile acids, biliary cholesterol is transported in nonmicellar aggregates, Finally, in the conditions of our study, taurohyodeoxycholic acid was not hepatotoxic.
1997
- Oral naltrexone treatment for cholestatic pruritus: a double-blind, placebo-controlled study
[Articolo su rivista]
F. H. J., Wolfhagen; E., Sternieri; W. C. J., Hop; Vitale, Giovanni; Bertolotti, Marco; H. R., van Buuren
abstract
Background & Aims: The efficacy of currently available therapeutic: agents for cholestatic pruritus is often disappointing. The aim of this study was to assess the antipruritic effect of naltrexone, an oral opiate receptor antagonist. Methods: Sixteen patients with pruritus of chronic cholestasis were randomized to receive naltrexone (4-week course of 50 mg naltrexone daily) or placebo, Pruritus, duality of sleep, fatigue (using visual analogue scales), side effects, and liver function were assessed every 2 weeks. Serum naltrexone and 6 beta-naltrexol concentrations in all patients and 5 healthy controls were measured during the first day of naltrexone treatment. Results: Mean changes with respect to baseline were significantly different, in favor of the naltrexone group, for daytime itching (-54% vs, 8%; P < 0.001) and nighttime itching (-44% vs. 7%, P = 0.003). In 4 naltrexone-treated patients, side effects (transient in 3 cases) consistent with an opiate withdrawal syndrome were noted. No deterioration of the underlying disease was observed. Naltrexone and 6 beta-naltrexol levels did not differ between patients and controls, and there was no significant association with treatment response. Conclusions: For patients with cholestatic liver disease and itching, refractory to regular antipruritic therapy, oval naltrexone may be an effective and well-tolerated alternative.
1996
- Bile acid structure and regulation of biliary protein secretion and composition in man
[Articolo su rivista]
M., Bozzoli; Loria, Paola; Carubbi, Francesca; M., Concari; M. E., Guicciardi; Bertolotti, Marco; Tagliafico, Enrico; Carulli, Nicola
abstract
To evaluate the effect of bile acid structure on total protein secretion and composition, 4 different bile acids, deoxycholic acid, chenodeoxycholic acid, cholic acid and ursodeoxycholic acid, in order of decreasing hydrophobicity, were infused intraduodenally in 5 cholecystectomized T-tube patients with interrupted enterohepatic circulation, Concentration and composition of biliary proteins were evaluated before and after acute substitution of the endogenous bile acid pool with each bile acid, Total biliary protein concentration and secretion increased progressively with increasing hydrophobicity of the infused bile acid and was highest for deoxycholic acid, followed by chenodeoxycholic acid, cholic acid and ursodeoxycholic acid, A significant increase in the 120 and 150 kDa protein bands on gel-electrophoresis was found after infusion with the more hydrophobic bile acids (deoxycholic acid and chenodeoxycholic acid), Quantitative and qualitative changes in biliary proteins, associated with the administration of bile acids that have different physico-chemical structures, may be relevant to the process of cholesterol crystal nucleation and the:pathogenesis of gallstone formation.
1996
- Effect of hypocholesterolemic doses of 17 alpha-ethinyl estradiol on cholesterol balance in liver and extrahepatic tissues
[Articolo su rivista]
Bertolotti, Marco; Spady, Dk
abstract
This study was performed to investigate the effects of 17 alpha-ethinyl estradiol, a potent hypocholesterolemic agent at pharmacological doses, on cholesterol balance in the liver and extrahepatic tissues of the rat in vivo. Female Sprague-Dawley rats were treated with 17 alpha-ethinyl estradiol (5 mg/kg per day s.c. for 5 days) or with 4-aminopyrazolo(3,4-d)pyrimidine (20 mg/kg per day i.p. for 3 days). Both drug regimens suppressed plasma total and low density lipoprotein-cholesterol by more than 80%. Analysis of the kinetic parameters of low density lipoprotein transport did not show increased receptor activity in extrahepatic tissues during either treatment. 17 alpha-Ethinyl estradiol significantly increased low density lipoprotein tissue spaces and clearance rates in the liver, with a 5-fold increase in low density lipoprotein-receptor activity, whereas 4-aminopyrazolo(3,4-d)pyrimidine suppressed hepatic transport of low density lipoprotein probably due to a nonspecific toxic effect. Treatment with 17 alpha-ethinyl estradiol markedly enhanced the hepatic expression of low density lipoprotein-receptor protein and mRNA despite a 7-fold increase in hepatic cholesteryl ester levels. Finally, treatment with both drugs increased cholesterol synthesis in several extrahepatic tissues, such as adrenals, ovaries, small bowel, and spleen. These findings confirm that 17 alpha-ethinyl estradiol at pharmacological doses markedly increases synthesis and expression of low density lipoprotein-receptor in the liver. Hypocholesterolemia, whether induced by activation of low density lipoprotein-receptors or by other mechanisms, fails to up-regulate low density lipoprotein transport in extrahepatic tissues, which rather respond by increasing local sterol synthesis. This suggests the occurrence of separate regulatory mechanisms for low density lipoprotein transport and cholesterol synthesis.
1996
- Effect of taurohyodeoxycholic acid on biliary lipid secretion in man: preliminary report.
[Articolo su rivista]
Loria, Paola; M., Bozzoli; M., Angelico; Bertolotti, Marco; Carubbi, Francesca; M., Concari; L., Baiocchi; A., Nistri; P., Della Guardia; M., Romani; Carulli, Nicola
abstract
Taurohyodeoxycholic acid and tauroursodeoxycholic acid were infused intraduodenally at a rate of 0.8 gk for three hours in 3 cholecystectomized T-tube patients, Biliary lipid secretion and bile acid composition were evaluated before and after replacement of the endogenous bile acid pool with the two bile acids. As compared to basal values (2.78+/-1.67 mM/l), taurohyodeoxycholic acid induced a greater increase in the biliary concentration of phospholipids (4.12+/-1.23 mM/l) as compared to tauroursodeoxycholic acid (3.14+/-0.98 mM/l). Biliary cholesterol concentration after taurohyodeoxycholic acid (1.89+/-0.63 mM/l) was unchanged as compared to the pretreatment period (1.98+/-0.58 mM/l), while it decreased significantly after tauroursodeoxycholic acid (0.85+/-0.08 mM/l). Biliary cholesterol secreted per unit of bile acid was greater during taurohyodeoxycholic acid than during tauroursodeoxycholic acid, while the opposite was observed for the secretion of phospholipids.
1995
- Effects of different phenotypes of hyperlipoproteinemia and of treatment with fibric acid derivatives on the rates of cholesterol 7alpha-hydroxylation in humans
[Articolo su rivista]
Bertolotti, Marco; M., Concari; Loria, Paola; N., Abate; Pinetti, Adriano; Me, Guicciardi; Carulli, Nicola
abstract
Little is known about the relationships between hyperlipidemia and bile acid metabolism. However, hypolipidemic treatment with fibric acid derivatives has been shown to increase biliary cholesterol secretion, presumably by reducing bile acid synthesis. To clarify such relationships, we investigated the effects of different hyperlipoproteinemic conditions and of treatment with fibric acid derivatives on the rates of cholesterol 7 alpha-hydroxylation (the limiting step of bile acid synthesis) in humans. We studied 10 patients (aged 36 to 68 years) with lipoprotein phenotype IIa and with a clinical diagnosis of heterozygous familial hypercholesterolemia, a condition of reduced activity of LDL receptors, and 11 patients (aged 48 to 70 years) with lipoprotein phenotype IIb or IV and clinical diagnosis of familial combined hyperlipidemia, a condition probably related to increased hepatic lipoprotein synthesis. Cholesterol 7 alpha-hydroxylation rates were assayed in vivo by tritium release assay after an intravenous injection of [7 alpha-H-3]cholesterol. The results were compared by ANOVA to the values obtained in a group of 28 normolipidemic patients (aged 34 to 83 years), with age as the covariate. Six patients were also studied after treatment with gemfibrozil (900 to 1200 mg/d for 6 to 8 weeks) and 5 patients were studied after treatment with bezafibrate (400 mg/d for 6 to 8 weeks). Hydroxylation rates were 0.82 +/- 0.22 mmol/d in the familial hypercholesterolemia group and 1.30 +/- 0.47 mmol/d in the familial combined hyperlipidemia. group (P < .05 between the two groups and between patients with familial combined hyperlipidemia and control subjects; P = NS between patients with familial hypercholesterolemia and control subjects, as determined by ANOVA). Treatment with both gemfibrozil and bezafibrate reduced serum cholesterol, slightly increased HDL cholesterol, and significantly reduced serum triglyceride and apo B concentrations. Cholesterol 7 alpha-hydroxylation rates were significantly reduced by nearly 55% both after gemfibrozil and after bezafibrate. Our findings indirectly suggest that cholesterol degradation to bile acid is independent of receptor-mediated uptake of LDL by the liver. Hydroxylation rates seem to parallel serum levels of triglyceride and apo B (particularly after fibrate treatment), possibly suggesting a coordinate reg ulation of bile acid and lipoprotein synthesis.
1995
- REGULATION OF HEPATIC CHOLESTEROL-METABOLISM IN THE RAT IN-VIVO. EFFECT OF A SYNTHETIC FAT-FREE DIET ON STEROL SYNTHESIS AND LOW-DENSITY-LIPOPROTEIN TRANSPORT
[Articolo su rivista]
Bertolotti, Marco; Spady, Dk; Dietschy, Jm
abstract
A synthetic fat-free diet, previously shown to decrease hepatic cholesterol synthesis, was utilized to manipulate cholesterol balance in vivo in female Sprague-Dawley rats. A significant 65% decrease of hepatic cholesterol synthesis compared to controls was shown after 1 week of treatment, which remained constant during the following 3 weeks. The inhibitory effect of the diet was completely abolished by cholestyramine supplementation. At week 3 of the experimental diet, bile acid synthesis was reduced by 63%, this reduction being correlated with decreased recycling frequency of the bile acid pool. Hepatic clearance of low-density lipoprotein (LDL) was slightly decreased, with no changes in plasma cholesterol, hepatic LDL-cholesterol uptake and whole body LDL-cholesterol production. When cholesterol and saturated fatty acids were supplemented to the diets in the attempt to disclose alteration in LDL transport, LDL clearance was unaffected; plasma LDL-cholesterol and hepatic LDL-cholesterol uptake were increased, as a consequence of increased LDL-cholesterol production. On the other hand, hepatic cholesterol synthesis was further suppressed; bile acid synthesis was increased by cholesterol supplementation in the fat-free group, even if to subnormal levels. These findings suggest that: (1) bile acid synthesis is decreased by feeding a synthetic fat-free diet, probably due to slower recirculation of bile acids along the entero-hepatic axis in conditions of reduced functional need; (2) consequently, a significant reduction of hepatic cholesterol synthesis is observed with no changes in LDL-cholesterol uptake; (3) further supplementation of dietary cholesterol and saturated fats is compensated for by changes in the rates of cholesterol and bile acid synthesis, but not of LDL transport. The data confirm the existence of independent regulation for hepatic sterol synthesis and LDL transport in this species.
1995
- Regulation of bile acid synthesis in humans: studies on cholesterol 7alpha-hydroxylation 'in vivo'
[Articolo su rivista]
Bertolotti, Marco; N., Abate; Loria, Paola; M., Concari; M. E., Guicciardi; M. A., Dilengite; M., Bozzoli; Carubbi, Francesca; Carulli, Nicola
abstract
Over the last few years important progress has been made on the quantitation of cholesterol 7 alpha-hydroxylation, the rate-limiting step of bile acid synthesis. The use of a technique based on the determination of body water tritium enrichment after i.v. administration of [7 alpha-H-3] cholesterol has allowed in vivo investigation of this step in humans in different experimental conditions, The cholesterol 7 alpha-hydroxylation rate was not affected by the administration of the hydrophilic bile acid ursodeoxycholic acid (UDCA) whereas it was significantly reduced by the more hydrophobic chenodeoxycholic acid (CDCA) and even more so by the strongly hydrophobic deoxycholic acid (DCA). The administration of cholestyramine induced a significant dose-related increase of 7 alpha-hydroxylation along with a correspondent decrease in plasma cholesterol, The administration of simvastatin exerted no effect on cholesterol 7 alpha-hydroxylation despite a marked decrease in serum cholesterol, Treatment with fibrates reduced plasma lipid levels and 7 alpha-hydroxylation rates, Hydroxylation rates were unchanged in familial hypercholesterolaemia and increased in familial combined hyperlipidaemia. These data suggest that in humans bile acid synthesis can be affected by quantitative and qualitative alterations of the enterohepatic circulation of bile acids. Changes in cholesterol 7 alpha-hydroxylation rates may be associated with alterations in plasma lipid levels, bat such a relationship is ill-defined and seems to vary with the different experimental models.
1994
- Anatomia e fisiologia delle vie biliari
[Articolo su rivista]
Loria, Paola; Bozzoli, M; Bertolotti, Marco; Carubbi, Francesca; Carulli, N; Bagni, A.
abstract
No Abstract
1994
- Drug metabolism in liver cirrhosis: alterations of the time-course of plasma naltrexone levels after oral intake
[Abstract in Rivista]
Bertolotti, Marco; Ferrari, Anna; Vitale, Giovanni; Stefani, M; Trenti, T; Loria, Paola; Carulli, N; Sternieri, E.
abstract
In liver cirrhosis significant changes in the serum levels of naltrexone and 6-beta-naltrexolare are observed. These alterations are related to the severity of liver disease
1994
- EFFECT OF CHENODEOXYCHOLIC ACID AND URSODEOXYCHOLIC ACID ADMINISTRATION ON ACYL-COA - CHOLESTEROL ACYLTRANSFERASE ACTIVITY IN HUMAN LIVER
[Articolo su rivista]
Abate, N; Carubbi, Francesca; Bozzoli, M; Bertolotti, Marco; Farah, I; Rosi, A; Carulli, Nicola
abstract
In order to investigate the relationship between bile acid pool composition and hepatic cholesterol metabolism in humans, we studied the effect of chronic feeding of chenodeoxycholic (CDCA) or ursodeoxycholic acid (UDCA) on the hepatic activity of acyl-CoA: cholesterol acyltransferase (ACAT) evaluated ''in vitro''. Twenty-eight gallstone patients were admitted to the study: 15 were untreated subjects, 8 were treated with UDCA (10 mg/kg/day for 15-20 days) and 5 were treated with CDCA (15 mg/kg/day for 15-20 days). A liver specimen and a bile sample were obtained during laparotomy for elective cholecystectomy. Untreated subjects had bile supersaturated with cholesterol (mean saturation index: 1.35 +/- 0.31) whereas subjects treated with either UDCA or CDCA had bile unsaturated with cholesterol (mean saturation index: 0.66 +/- 0.1 and 0.75 +/- 0.06 respectively). In all treated subjects the bile acid administered became predominant in bile. ACAT activity was 14% lower in subjects treated with UDCA and 16% lower in those treated with CDCA compared to controls; the differences did not achieve statistical significance. Microsomal cholesterol content did not differ between the groups (75.4 +/- 7.2 nmol/mg protein in control group; 86.5 +/- 7.0 nmol/mg protein in CDCA treated group; 83.4 +/- 7.0 nmol/mg protein in UDCA treated group). Our data show that the cholesterol esterifying activity of human liver is not affected by changes in bile acid pool composition.
1994
- Effect of Chenodeoxycholic acid and Ursodeoxycholic acid administration on acyl-CoA: cholesterol acyl tranferase activity in human liver.
[Articolo su rivista]
Abate, N.; Carubbi, Francesca; Bozzoli, M.; Bertolotti, Marco; Farah, I.; Rosi, A.; Carulli, N.
abstract
Chenodeoxycholic acid and Ursodeoxycholic acid administration on acyl-CoA: cholesterol acyl tranferase activity in human liver.
1994
- Effect of diabetic autonomic neuropathy on gallbladder kinetics in insulin dependent diabetic patients
[Articolo su rivista]
Dilengite, Ma; Loria, Paola; Menozzi, D; Tripodi, A; Giucciardi, L; Digrisolo, A; Bertolotti, Marco; Bozzoli, M; Carubbi, Francesca; Carulli, Nicola
abstract
Objective: To evaluate the relationship between autonomic nervous system involvement and gall bladder contraction in insulin-dependent diabetic patients. Patients and methods: Fasting gall bladder volume and gall bladder emptying in response to a standard liquid meal were evaluated using ultrasonography in 10 normal subjects and in 35 patients with insulin-dependent diabetes: 10 without, 15 with asymptomatic and 10 with symptomatic autonomic neuropathy (AN). Gall bladder volumes were calculated from ultrasonographic images, taken during fasting and at regular intervals after a standard meal, using the sum of cylinders method. Evaluation of the presence and degree of AN was based on standard tests and clinical history. Results: In controls, the mean fasting gall bladder volume was 1 7.6 +/- 3.7 ml, while respective values for residual volume, per cent emptying and emptying rate were: 3.63 +/- 1.69 ml, 77.3 +/- 10.7% and 0.0356 +/- 0.0121 min-1. Compared with controls, diabetic patients had a slightly higher fasting gall bladder volume (19.1 +/- 5.6 ml), while values for residual volume, per cent emptying and emptying rate were significantly altered at: 9.79 +/- 5.90 ml, 50.7 +/- 18.2% and 0.0155 +/- 0.0070 min-1, respectively (P<0.01). When diabetic patients were grouped according to the degree of AN, values for fasting gall bladder volume were significantly higher in those with symptomatic AN (22.0 +/- 7.7 ml) compared with controls (P<0.05). When compared with controls, patients without AN had a significantly (P<0.01) higher residual volume (5.58 +/- 1.96 ml), a significantly lower value for per cent emptying (65.3 +/- 11.3%) and a prolonged emptying rate (0.0213 +/- 0.0055 min-1). Gall bladder motility deteriorated progressively in diabetic patients with asymptomatic and symptomatic neuropathy. In the latter group, gall bladder emptying was greatly compromised, with a residual volume of 15.22 +/- 8.10 ml, and per cent emptying and emptying rate of 32.8 +/- 19.8% and 0.0060 +/- 0.0030 min-1, respectively (P<0.01 versus controls and diabetic patients with and without asymptomatic AN). Conclusions: Impairment of gall bladder contraction in diabetic patients seems to be dependent on the presence of AN. However, the presence of an alteration in gall bladder motility in those without neuropathy suggests that other factors could also play a role in gall bladder contraction in diabetic patients.
1994
- Headache patients’ attitude toward analgesic drugs
[Relazione in Atti di Convegno]
Ferrari, Anna; Stefani, M; Bertolotti, Marco; Sternieri, S; Trenti, T; Sternieri, E.
abstract
The majority of our patients had a positive attitude towards over-the-counter analgesics, which they believed to be more adequate than prescription drugs for acute treatment of their headache. They handled analgesics very carefully, believing it correct to take the drug only when the pain became unbearable, if it was not possible for them to stop work. Chronic headache patients tended to consume more prescription drugs than episodic headache sufferers. Furthermore, the majority of chronic sufferers, as opposed to episodic sufferers, took the analgesic even when not at work.
The use of over-the-counter drugs is considered the best way to treat acute headache even by subjects suffering from severe idiopathic headache and seeking professional care in specialized clinics. Prescribed analgesics are underused by patients with serious episodic headache, which is precisely the group for which they are principally intended.
1994
- Naltrexone and 6-Beta-naltrexol concentration/time profile in the treatment of opiate dependence
[Abstract in Rivista]
Ferrari, Anna; Bertolotti, Marco; Trenti, T; Vitale, Giovanni; Stefani, M; Sternieri, E.
abstract
The time-course of naltrexone and 6-beta-naltrexol did not change after month of naltrexone treatment in heroin addicts
1994
- Naltrexone: aspetti di farmacologia ed applicazioni cliniche
[Articolo su rivista]
Sternieri, E; Ferrari, Anna; Bertolotti, Marco; Stefani, M; Vitale, Giovanni
abstract
L’azione farmacologica del naltrexone consiste in una inibizione competitiva a livello dei siti recettoriali per gli oppiacei, come è stato dimostrato in vitro su organi isolati (Leslie et al., 1979) ed in vivo nell’animale. Il Naltrexone produce l’effetto antagonista spostando le molecole dei morfinici a livello recettoriale e bloccandone l’accesso a livello dei recettori (Martin, 1968; Anou, 1978; Anou, 1982). La somministrazione a lungo termine di naltrexone determina un aumento del numero dei recettori cerebrali di tipo mu, kappa e delta (ma non sigma) (Tempel et al., 1982) ed una ipersensibilità recettoriale nel locus coeruleus che può essere accentuata da un successivo trattamento con morfina (Bardo et al., 1983).. Praticamente il naltrexone non ha attività agonista (Martin et al, 1973; O’Brin et al 1978; Gold et al 1982) e quindi la sospensione del suo uso non si associa a sintomi di astinenza (Anou, 1978), ma in alcuni studi in soggetti sani, non dipendenti da oppiacei, ha determinato un leggero grado di attività agonistica morfinica (miosi, depressione respiratoria, disforia) (Crabtree, 1984; Hollisten et al 1981, Mendelson et al, 1979).
1994
- Prevalence rates of gallstone disease in Italy: the Chianciano population study
[Articolo su rivista]
Loria, Paola; Ma, Dilengite; M., Bozzoli; Carubbi, Francesca; R., Messora; R., Sassatelli; Bertolotti, Marco; A., Tampieri; Pl, Tartoni; M., Cassinadri; M., Dellaciana; M., Contemori; N., Save; B., Sordi; G., Alimenti; F., Fabrizi; A., Buciuni; Carulli, Nicola
abstract
The prevalence of gallstone disease and associated factors in the entire population of subjects aged 15-65 years born and resident in Chianciano Terme (Siena - Tuscany) was examined in the years 1985 and 1986. The investigation included gallbladder ultrasonography, administration of a questionnaire on personal and family history, physical examination and blood chemistry. A total of 1809 subjects (attendance rate 87.7%) participated in the study. Personal history and physical examination showed that Chianciano inhabitants have a low prevalence of obesity (4.3%) and only 4.4% of the female population had more than two pregnancies. Overall prevalence of gallstone disease (cholecystectomy + cholelithiasis) was 5.9% (3.7% for males and 8.4% for females). Age standardized relative risk of gallstone disease for females was 2.25 (95% confidence limits = 1.68-2.68). Prevalence of cholelithiasis was 3.5% (2.7% for males and 4.2% for females). Prevalence of gallstone disease increased with increasing age in both sexes, being extremely low in the age interval of 15-29 years (0.25%). The overall gallstones/cholecystectomy ratio was found to be lower(l:l) in females than in males (2.7:1). Although subjects with gallstones reported more frequently biliary colics and nonspecific dyspeptic symptoms, the diagnostic power of all symptoms in identifying cholelithiasis was very poor due to low sensitivity. Only one third of subjects with gallstones was aware of having the disease. Age, obesity and number of pregnancies were positively associated with gallstone disease in univariate analyses. The association with obesity and parity disappeared in multivariate analysis. Blood lipids and glucose were not associated with the disease both in univariate and multivariate analyses. Our data show that the prevalence of gallbladder disease in Chianciano is lower than that previously reported in italy. This difference could be related to a lower prevalence of obesity and to a smaller number of pregnancies or to the effect of environmental and genetic factors.
1994
- Prevalenza e frequenza dell’uso di cocaina in un campione di tossicodipendenti del territorio modenese
[Articolo su rivista]
Ferrari, Anna; Bertolotti, Marco; Poppi, B; Trenti, T; Nuzzo, C; Ferretti, C; Sternieri, E.
abstract
Nel corso del 1992 abbiamo studiato, mediante la somministrazione di un questionario e l'analisi delle urine, la diffusione e le modalità dell'abuso di cocaina in un campione di 185 tossicodipendenti formato da soggetti ricoverati nei reparti del policlinico, detenuti presso la casa circondariale e nuovi utenti del servizio per le tossicodipendenze dell'USL 16 di Modena.
La prevalenza dell'uso di cocaina nella vita era dell'82% e significativamente più elevata tra i ricoverati (95%) rispetto ai detenuti (75%) e ai nuovi utenti del SERT (66%). Non vi erano differenze tra maschi e femmine. Il 39% del campione dichiarava di assumere cocaina solo per via nasale, il 61% per più vie di assunzione; il 16% usava in vena cocaina ed eroina insieme. Il 10% dei campioni di urine esaminati risultava positivo per la cocaina e/o i suoi metaboliti.
I risultati del nostro studio indicano che l'abuso di cocaina è comune tra i dipendenti da eroina dell'area modenese.
1994
- Regulation of bile acid synthesis in humans
[Relazione in Atti di Convegno]
Bertolotti, Marco; Abate, N.; Loria, Paola; Dilengite, M.; Carubbi, Francesca; Bozzoli, M.; Carulli, N.
abstract
regulation of bile acid synthesis is studied by determination of 7 alpha hydroxylase activity in vivo in humans
1994
- Short-term effects of simvastatin on bile acid synthesis and biliary lipid secretion in human subjects.
[Articolo su rivista]
Loria, Paola; Bertolotti, Marco; Cassinadri, M. T.; Dilengite, M. A.; Bozzoli, M.; Carubbi, Francesca; Concari, M.; Guicciardi, M. E.; Carulli, N. .
abstract
To test whether de novo synthesis of cholesterol is a limiting factor for bile acid synthesis, we studied the acute effect of simvastatin, an inhibitor of HMG-coenzyme A reductase (the limiting step of cholesterol synthesis) on bile acid synthesis and biliary lipid secretion in subjects with interrupted enterohepatic circulation. In these conditions bile acid synthesis is derepressed and is assumed to equal biliary bile acid secretion. Five cholecystectomized patients fitted with T-tubes were studied. All subjects were administered simvastatin (80 mg as a single dose) 5 days after surgery. Bile was collected in 3-hr intervals for 15 hr before and 30 hr after the administration of the drug. During the experiment we kept the enterohepatic circulation of bile acid interrupted by inflating an occludable balloon inserted, during cholecystectomy, in the common bile duct. Simvastatin induced significant decreases of plasma total and low density lipoprotein cholesterol concentrations, from 163 +/- 29 mg/dl and 97 +/- 24 mg/dl of the pretreatment value to 144 +/- 30 mg/dl and 82 +/- 22 mg/dl 18 hr after simvastatin administration, respectively. Bile flow tended to increase after simvastatin, and the mean values from the third to the 15th hour after simvastatin administration (22.1 +/- 1.9 ml/hr) were significantly greater than the mean values of the pretreatment period (19.9 +/- 2.8 ml/hr). Concomitantly biliary bile acid, cholesterol and phospholipid concentrations fell from basal values of 15.9 +/- 5.1, 2.3 +/- 0.3 and 5.5 +/- 0.3 mmol/L to mean values, after treatment, of 9.0 +/- 3.5, 1.9 +/- 0.5 and 3.0 +/- 0.9 mmol/L, respectively
1993
- Disposition of naproxen after oral administration during and between migraine attacks.
[Articolo su rivista]
PINI, Luigi Alberto; BERTOLOTTI, Marco; Trenti, T; VITALE, Giovanni
abstract
Naproxen is an anti-inflammatory drug widely used in the management of pain and in the treatment of migraine and headache. As gastrointestinal disturbances are a common feature of migraine, the aim of this study was to evaluate the absorption and the efficacy of naproxen administered during migraine attacks. Ten patients were treated with 500 mg of a soluble form of naproxen during and between migraine attacks. Clinical parameters and drug plasma levels were recorded at scheduled times. Pain reduction, from severe to mild was evident by 6.5 +/- 3.4 hours and the total pain score showed a reduction from 2 hours onwards. Pharmacokinetic data showed a slight delay in drug absorption during attacks (absorption half-life and time of maximum drug concentration were increased during attacks), but overall bioavailability of naproxen, as reflected by area under the curve (AUC) and maximum plasma drug concentration were unchanged. Since pain relief was reported, it may be concluded that delayed absorption has little or no influence on the therapeutic effect of naproxen in migraine attacks in fasting patients.
1993
- Effect of aging on cholesterol 7 alpha-hydroxylation in humans
[Articolo su rivista]
Bertolotti, Marco; N., Abate; S., Bertolotti; Loria, Paola; M., Concari; R., Messora; Carubbi, Francesca; A., Pinetti; Carulli, Nicola
abstract
In order to investigate the alterations of bile acid synthesis in aging, we studied the rates of cholesterol 7 alpha-hydroxylation, the rate-limiting step, in 28 patients of different ages (34-83 years old, 14 below and 14 above the age of 65) of both sexes. Hydroxylation rates were determined by tritium release assay after an intravenous bolus of [7 alpha-3H]cholesterol. Cholesterol 7 alpha-hydroxylation was significantly decreased in the older age group, compared to middle-aged subjects, both in males and females; moreover, a significant inverse correlation between hydroxylation rates and age was found in the whole sample (r = -0.56; P < 0.01) and in females, but not in males. The percent concentration of deoxycholic acid in plasma (determined by gas-liquid chromatography) was increased in older subjects. Plasma cholesterol and triglyceride levels were not related with age even though triglyceride concentrations tended to be lower in the older age group. Triglyceride, but not cholesterol levels, were directly correlated with hydroxylation rates (r = 0.45, P < 0.05). After cholestyramine treatment (8-12 g/day for 4 weeks) a sharp increase in 7 alpha-hydroxylation rates was observed in three elderly patients, accompanied by reduced levels of dihydroxylated bile acids. Our data are consistent with a reduced rate of conversion of cholesterol to bile acids with aging, particularly in females, and suggest a coordinate reduction of triglyceride production. Alterations of the quantitative and/or qualitative pattern of the bile acid pool recirculating to the liver may be responsible, at least in part, for the changes observed.
1993
- Plasma reduced glutathione and cysteine levels in heroin addicts
[Abstract in Rivista]
Trenti, T; Bertolotti, M; Ferrari, A; Pini, L. A.; Sternieri, E.
abstract
Experimental evidence that in the metabolism of heroin there is a decrease in plasma GSH
1993
- Plasma time-course of naltrexone and 6beta-naltrexol after oral naltrexone administration in patients with liver cirrhosis
[Abstract in Atti di Convegno]
Bertolotti, Marco; Ferrari, Anna; Vitale, Giovanni; Trenti, T; Carulli, N; Sternieri, E.
abstract
BACKGROUND/AIMS: Naltrexone has been proposed as a possible treatment of pruritus in cholestasis.These studies were undertaken to evaluate the effect of liver cirrhosis on the plasma time-course of naltrexone.
METHODS: A total of 18 patients were investigated: seven migraine patients with normal liver function regarded as controls and 11 patients with liver cirrhosis (six with decompensated disease and five with preserved liver function). Serum levels of naltrexone and of its major active metabolite, 6 beta-naltrexol, were assayed by reversed-phase HPLC analysis.
RESULTS: In control subjects, circulating concentrations of naltrexone were always much lower than those of 6 beta-naltrexol (area under the curve: naltrexone, 200 +/- 97 ng/ml x 24 h; 6 beta-naltrexol, 2467 +/- 730 ng/ml x 24 h, p < 0.01). In severe cirrhosis serum levels of 6 beta-naltrexol increased more slowly, so that circulating levels of naltrexone during the first 2-4 h after drug intake were higher than those of 6 beta-naltrexol (6 beta-naltrexol/naltrexone ratio at 2 h: controls, 10.91 +/- 4.80; cirrhosis, 0.39 +/- 0.18, p < 0.01). The area under the curve for naltrexone (1610 +/- 629 ng/ml x 24 h) was significantly greater than in controls, whereas that for 6 beta-naltrexol (2021 +/- 955 ng/ml x 24 h) was not significantly different. Patients with compensated cirrhosis showed an intermediate pattern. No differences in elimination half-life of the two drugs were detected among the groups.
CONCLUSIONS: Our data suggest the occurrence of important changes in the systemic availability of naltrexone and 6 beta-naltrexol in liver cirrhosis; such alterations are consistent with lesser reduction of naltrexone to 6 beta-naltrexol and appear to be related to the severity of liver disease. This must be considered when administering naltrexone in conditions of liver insufficiency.
1993
- Plasma time-course of naltrexone and 6beta-naltrexol levels after oral administration in drug addicts and in patients with liver cirrhosis
[Abstract in Rivista]
Bertolotti, M; Ferrari, A; Trenti, T; Vitale, G; Macchia, T; Carullin, ; Sternieri, E.
abstract
Abstract sulla cinetica del naltrexone
1993
- Serum levels of naltrexone and 6-beta-naltrexol after oral naltrexone in patients with liver cirrhosis
[Abstract in Rivista]
Bertolotti, Marco; Ferrari, Anna; Vitale, Giovanni; Trenti, T; Loria, P; Carulli, N; Sternieri, E.
abstract
liver cirrhosis induces important changes in the time-course of naltrexone with higher bioavailability of naltrexone and slower conversion to 6-beta-naltrexol
1993
- The decrease in plasma thiol groups in daily headache paracetamol abuser patients as possible factor of pain maintenance
[Abstract in Rivista]
Trenti, T; Bertolotti, Marco; Ferrari, Anna; Pini, Luigi Alberto; Sternieri, E.
abstract
We have assessed plasma GSH in patients using paracetamol daily. In these patients a significant lower plasma GSH concentration was found with respect to controls. After the i.v. administration of GSH free plasma cysteine was 12 fold higher than in basal condition and all the pattern of plasma thiol groups was modified. This work suggests that the possible protective effect of GSH administration is due to the availability of plasma thiol compounds that enter the cell rather than GSH itself.
1992
- Lipids and serum apoproteins in subjects with slight or mild coronary atherosclerosis evaluated with angiography
[Articolo su rivista]
Magnavacchi, P.; Boiardi, L.; Barbagallo, M.; Novo, S.; Bertolotti, M.; Benassi, A.; Butturini, L.; Biagi, R.; Pedrazzini, F.; Barbagallo, C. M.
abstract
In this study 126 subjects (91 males and 35 females, range of age 43-65 years) were studied by coronary angiography. We considered positive for coronary atherosclerosis also patients showing mild or moderate stenosis (> or = 25%). In all subjects we have evaluated serum lipid and apoprotein A-I, B, C-II, C-III and E levels; therefore also cholesterol concentrations in all lipoprotein fractions, separated by sequential ultracentrifugation (VLDL d < 1.006, LDL d 1.006-1.063, HDL d > 1.063 g/ml) and apoprotein B in LDL have been measured. Subjects with coronary atherosclerosis have shown significantly higher levels of total cholesterol, LDL-cholesterol, total cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol ratios than controls. Therefore, a lower apo A-I/apo B ratio in males and a higher LDL-apo B levels in females has been found in subjects with coronary atherosclerosis in comparison with controls. The stepwise multiple analysis has demonstrated that LDL-cholesterol levels is the parameter that best correlates with the presence of coronary atherosclerosis. These data confirm the importance of the reduction of LDL-cholesterol levels in primary and secondary prevention of coronary heart disease.
1992
- PHARMACOKINETIC OF REDUCED GLUTATHIONE IN MAN - EFFECT ON PLASMA CYSTEINE AND THIOL COMPOUNDS
[Articolo su rivista]
Trenti, T; Bertolotti, Marco; Ferrari, Anna; Pini, Luigi Alberto; Sternieri, E.
abstract
No abstract available
1992
- PHARMACOKINETICS OF NAPROXEN AFTER ORAL-ADMINISTRATION DURING AND OUT OF MIGRAINE ATTACKS
[Articolo su rivista]
Pini, Luigi Alberto; Bertolotti, Marco; Trenti, T; Sternieri, E.
abstract
Naproxen is an anti-inflammatory drug widely used in the management of pain and in the treatment of migraine and headache. As gastrointestinal disturbances are a common feature of migraine, the aim of this study was to evaluate the absorption and the efficacy of naproxen administered during migraine attacks. Clinical parameters and drug plasma levels were recorded at scheduled times. Pain reduction, from severe to mild was evident by 6.5 +/- 3.4 hours and the total pain score showed a reduction from 2 hours onwards. Pharmacokinetic data showed a slight delay in drug absorption during attacks (absorption half-life and time of maximum drug concentration were increased during attacks), but overall bioavailability of naproxen, as reflected by area under the curve (AUC) and maximum plasma drug concentration were unchanged. Since pain relief was reported, it may be concluded that delayed absorption has little or no influence on the therapeutic effect of naproxen in migraine attacks in fasting patients.
1992
- Plasma concentrations of naltrexone and 6β-naltrexol in patients with liver cirrhosis and drug addicts in chronic treatment with naltrexone
[Articolo su rivista]
Ferrari, A.; Bertolotti, M.; Vecchi, M. C.; Trenti, T.; Sternieri, S.
abstract
1992
- Plasma glutathione level in paracetamol daily abuser patients. Changes in plasma cysteine and thiol groups after reduced glutathione administration
[Articolo su rivista]
Trenti, T; Bertolotti, Marco; Castellana, Cn; Ferrari, Anna; Pini, Luigi Alberto; Sternieri, Emilio
abstract
Since plasma reduced glutathione (GSH) seems to reflect liver GSH content, we have assessed plasma GSH in patients using paracetamol daily. In these patients a significant lower plasma GSH concentration was found with respect to controls. After the i.v. administration of GSH free plasma cysteine was 12 fold higher than in basal condition and all the pattern of plasma thiol groups was modified. This work suggests that the possible protective effect of GSH administration is due to the availability of plasma thiol compounds that enter the cell rather than GSH itself.
1992
- Serum naltrexone and 6-beta naltrexol concentrations in detoxified addicts during long term naltrexone treatment
[Articolo su rivista]
Ferrari, Anna; Trenti, T; Macchia, T; Dell'Utri, A; Sternieri, E; Avico, U; Ferretti, C; Bertolotti, Marco
abstract
The pourpose of the present study was to evaluate naltrexone and 6-b-naltrexol plasma time course during long term treatment in the usual clinical setting, in drug addicts. The plasma levels of naltrexone and 6-b-naltrexol were determined for 24 hours following an oral dose of 100 mg at the beginning and after months of naltrexone treatment.
Our results showed large differences among patients in serum naltrexone and 6b-naltrexol levels. On the other hand, there were no differences in serum time course of both substances in the same patient over 3 months. Peak levels and AUCs of naltrexone were lower than those of 6b-naltrexol in 10 addicts and higher than those of the metabolite in 3 patients. No significant differences in the apparent half-lives of the two drugs were detected among groups. These data are consistent with the occurrence of a decreased first-pass metabolism of naltrexone in 3 patients leading to a larger availability of an oral dose.
1991
- Advances in the comprehension of the pathophysiology of bile secretion
[Articolo su rivista]
Loria, Paola; Bertolotti, Marco; A., Tripodi; Ma, Dilengite; Carulli, Nicola
abstract
(No Abstract)
1991
- Interactions between chronic headache and analgesic drug overuse: clinical and toxicological aspects
[Articolo su rivista]
Ferrari, Anna; Bertolotti, Marco; Malferrari, G; Pini, Luigi Alberto; Trenti, T; Sternieri, E.
abstract
Usually overuse of analgesic drugs in chronic headache sufferers is seen only as a secondary or accesssory event complicating headache. We instead believe that the two phenomena are closely interrelated, so to generate a "loop" from which important clinical and toxicologial implication can derive. On the basis of these considerations the aim of our research was to descrive the complex interactions between patient, chronic headache and analgesic drug.
The combination of indomethacin plus caffeine plus prochlorperazine, and triptans were the medications most frequently overused by our patients; only a few patients overused ergot preparations. The majority of patients used the same type of drug daily. All patients referred they increased the frequency of self-medication because the headaches were getting worse. For most patients medication overuse made the headache more endurable, thus allowing them to work orfunction more or less normally in daily life. Only a minority experiencedwithdrawal symptoms after discontinuation of the medication overuse. After detoxification, antidepressants were the class of drugs most used for prophylaxis.
1991
- Pharmacological outline of chronic headache patients: overlap between depressive and nociceptive symptomatology
[Capitolo/Saggio]
Sternieri, Emilio; Guaraldi, Gp; Mazzi, Fausto; Venuta, Marco; Orlandi, Emanuele; Trenti, T; Bertolotti, Marco; Ferrari, Anna; Pini, Luigi Alberto
abstract
This book is a collection of 30 chapters of widely varying subject matter—the unifying theme being that these chapters deal with depression, headache, or both. Sections include the following: neurochemistry of 5-hydroxytryptamine pathways, with four excellent chapters on this subject and review of findings as they relate to headache, depression, and pain; chronic headache and mood disorders, four primarily clinical chapters with a brief, interesting review of pain threshold studies; periodicity of affective and headache disorders, with chapters on seasonal cycles found in depression, menstrual cycles in mood and headache, and effects of different treatments; drugs affecting the serotonergic system (seven chapters of widely varying quality) with three review articles, one (by Sicuteri) giving a summary of his overall formulation of central pain systems, another summarizing data on serotonin and depression, and three subsequent studies briefly reporting results on specific pharmacologic agents
1991
- Regulation of bile acid synthesis in humans: effect of treatment with bile acids, cholestyramine or simvastatin on cholesterol 7 alpha-hydroxylation rates in vivo.
[Articolo su rivista]
Bertolotti, Marco; N., Abate; Loria, Paola; M., Dilengite; Carubbi, Francesca; Pinetti, Adriano; A., Digrisolo; Carulli, Nicola
abstract
The rates of cholesterol 7-alpha-hydroxylation (the first and rate-limiting step of bile acid synthesis from cholesterol) were evaluated in vivo in patients administered bile acids with different structural properties, cholestyramine or simvastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Twenty-three subjects, with normal hepatic and intestinal functions, were studied in basal conditions and after one of the following treatment schedules, lasting 4 to 6 weeks: cholestyramine, 4 and 12 gm/day (four patients); ursodeoxycholic acid, 9 to 11 mg/kg/day (four patients); chenodeoxycholic acid, 12 to 15 mg/kg/day (five patients); deoxycholic acid, 8 to 10 mg/kg/day (four patients); and simvastatin, 40 mg/day (six patients). 7-alpha-Hydroxylation of cholesterol was assayed by measuring the increase in body water tritium after intravenous bolus of cholesterol tritiated at the 7-alpha position. Plasma bile acid composition, evaluated by gas-liquid chromatography, revealed a substantial enrichment of the recirculating pool by the administered bile acid, whereas treatment with cholestyramine decreased the content of dihydroxylated bile acids. Cholesterol 7-alpha-hydroxylation increased in a dose-related manner after cholestyramine, in parallel with a decrease of cholesterol in total plasma and low-density lipoproteins (1.006 to 1.063 gm/ml). Hydroxylation rates decreased by an average of 47% with chenodeoxycholic acid and by an average of 78% with deoxycholic acid; ursodeoxycholic acid treatment did not affect 7-alpha-hydroxylation significantly. Simvastatin markedly reduced plasma total and low-density lipoprotein-cholesterol but exerted no change on 7-alpha-hydroxylation rates. Our results support the existence of a feedback inhibition exerted on cholesterol 7-alpha-hydroxylation (and consequently on bile acid synthesis) by hydrophobic bile acids returning to the liver through the enterohepatic circulation. The finding emphasizes the importance of the physicochemical properties of bile acids in the regulation of hepatic cholesterol balance. Under these experimental conditions, inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and presumably reduced availability of newly synthesized cholesterol are not critical for bile acid synthesis.
1990
- BILE CHANGES DURING TREATMENT WITH DEOXYCHOLIC-ACID - REPLY
[Articolo su rivista]
Bertolotti, Marco; Carulli, Nicola
abstract
Letter reply
1990
- Effects of bile acid pool composition on hepatic metabolism of cholesterol in man
[Articolo su rivista]
Carulli, Nicola; Loria, Paola; Bertolotti, Marco; Carubbi, Francesca; A., Tripodi; N., Abate; M., Dilengite
abstract
This work reviews the evidence concerning the role of the bile acid pool composition in the regulation of the overall hepatic metabolism of cholesterol in man. It has been known that bile acids regulate bile secretion, biliary lipid transport and hepatic cholesterol metabolism. However, the intimate mechanisms of these regulatory functions are not well understood. Current thinking attributes most of this regulation to the size of the bile acid pool. A typical example is represented by the negative feed-back mechanism by which bile acids returning to the liver control their own synthesis. Recent evidence however tend to suggest that not only the size but also the composition contributes to the regulatory activity of the bile acid pool. Specifically the hydrophobic-hydrophilic balance of the pool, as resulting from the characteristics and the proportions of the individual bile acids present within the pool, seems to dictate most of the effects of bile acids on hepatic cholesterol metabolism. Thus abundance within the pool of hydrophobic bile acids, such as deoxycholic or chenodeoxycholic acid, seems to induce a greater biliary lipid secretion and to exert inhibition of cholesterol and bile acid synthesis whereas hydrophilic bile acids such as ursodeoxycholic acid seem to be uneffective. It follows that by changing the composition of the bile acid pool it is possible to influence the hepatic metabolism of cholesterol
1990
- PHARMACOKINETICS OF TIAPROFENIC ACID AFTER ORAL-ADMINISTRATION IN FASTING PATIENTS DURING AND BETWEEN MIGRAINE ATTACKS
[Articolo su rivista]
Pini, Luigi Alberto; Bertolotti, Marco; Bergonzini, G; Casalgrandi, L; Giroldi, L; Sternieri, E.
abstract
This study examined the pharmacokinetics of 300 mg of tiaprofenic acid, a NSAID belonging to the 2-arylpropionic class, as a single oral dose, in 10 migraine patients during and out of migraine attacks. Plasma concentration of tiaprofenic acid was determined by HPLC analysis. Drug absorption appeared to be the same during and out of migraine attacks (absorption half life: during attack, 0.249 +/- 0.122 hr; out of attack, 0.249 +/- 0.105 hr; maximum plasma concentration: during attack, 37.8 +/- 9.8 ug/ml; out of attack, 40.1 +/- 13.2 ug/ml). The other pharmacokinetic parameters evaluated were not affected by headache attacks as well. We conclude that tiaprofenic acid absorption and metabolism are not affected by migraine attacks. Also, our data suggest that tiaprofenic acid might be useful in the treatment of migraine
1990
- PRIMARY NON-HODGKINS-LYMPHOMA OF THE ESOPHAGUS
[Articolo su rivista]
Mengoli, M; Marchi, M; Rota, E; Bertolotti, Marco; Gollini, C; Signorelli, S.
abstract
Case report
1989
- Patogenesi della colelitiasi. I. Colelitiasi colesterinica.
[Articolo su rivista]
Loria, Paola; Tripodi, A; Bertolotti, Marco; Carubbi, Francesca; Medici, G; Dilengite, Ma; Carulli, N.
abstract
no abstract
1989
- Pharmacokinetics of tia profenic acid in headache attacks - a preliminary report
[Articolo su rivista]
Pini, Luigi Alberto; Casalgrandi, L; Bertolotti, Marco; Giroldi, L.; Bergonzini, G.
abstract
This preliminary study examined the pharmacokinetics of 300 mg of tiaprofenic acid, in single oral dose, in 7 migraine patients during and out of migraine attacks. Plasma concentration of tiaprofenic acid was determined by HPLC analysis. The absorption phase did not differe between in and out migraine attacks.
also other pharmacokinetic parameters evaluated were not affected by headache attacks as well. We conclude that tiaprofenic acid absorption and metabolism are not affected by migraine attacks.
1988
- Bile acids and cholesterol metabolism: Effect of deoxycholic acid on plasma lipoprotein and biliary cholesterol concentration
[Articolo su rivista]
Bertolotti, M.; Iori, R.; Zironi, F.; Montanari, M.; Tripodi, A.; Carulli, N.
abstract
1987
- Il pool degli acidi biliari quale regolatore del metabolismo epatico del colesterolo: sintesi degli acidi biliari.
[Articolo su rivista]
Carulli, N; Bertolotti, Marco; Menozzi, D; Loria, Paola; Tripodi, A; Carubbi, Francesca
abstract
Supplemento "Progressi in Epatologia".
1986
- Effect of ursocholic acid on bile lipid secretion and composition
[Articolo su rivista]
Loria, Paola; Carulli, Nicola; Medici, G; Menozzi, D; Salvioli, G; Bertolotti, Marco; Montanari, M.
abstract
To further clarify the relationship between physical-chemical characteristics of bile acids and biliary lipid secretion, we investigated the effect of ursocholic acid, the 7 beta-hydroxyepimer of cholic acid, on bile lipid secretion and composition. The study included acute duodenal infusion (1 g/h for 5 h) of ursocholic acid contrasted with a less hydrophilic bile acid, ursodeoxycholic acid, in 3 T-tube patients and short-term oral administration (2 wk) of ursocholic acid (10-15 mg/kg X day) to 10 gallstone patients. Following acute infusion, ursocholic acid, similarly to ursodeoxycholic acid, accounted for greater than 80% of the biliary bile acids. However, ursocholic acid induced (per micromole of secreted bile acid) a significantly lower (p less than 0.01) secretion of cholesterol (0.013 mumol) and phospholipids (0.054 mumol) than that induced by ursodeoxycholic acid (0.034 mumol of cholesterol and 0.138 mumol of phospholipids). Biliary alkaline phosphatase activity during ursocholic acid administration was significantly lower (p less than 0.01) than during ursodeoxycholic acid administration. After short-term oral administration, ursocholic acid, undetectable before treatment, constituted 20.50% +/- 8.60% of the biliary bile acids. The percentage of deoxycholic acid increased from 32.35% +/- 18.79% to 47.53% +/- 16.19% (p less than 0.05). Mean saturation index decreased from a pretreatment value of 1.23 +/- 0.22 to 0.99 +/- 0.17 (p less than 0.05), but only in 4 of 10 subjects did bile become undersaturated. It is concluded that ursocholic acid, due to its higher hydrophilicity, stimulates a lower cholesterol and phospholipid output than ursodeoxycholic acid. Consequently, despite the low enrichment of the biliary bile acids with ursocholic acid, oral administration of ursocholic acid induces a reduction of bile cholesterol saturation.
1986
- In vivo evaluation of cholesterol 7 alpha-hydroxylation in humans: effect of disease and drug treatment
[Articolo su rivista]
Bertolotti, Marco; Carulli, Nicola; D., Menozzi; F., Zironi; A., Digrisolo; A., Pinetti; M. G., Baldini
abstract
7 alpha-Hydroxylation of cholesterol is a stereospecific reaction consisting of the replacement of the 7 alpha-hydrogen with a hydroxyl group. When cholesterol labeled with tritium at the 7 alpha position is administered, the hydroxylation of the substrate will result in the loss of tritium which in turn will label the body water. The rate of tritium enrichment of the body water could thus give a quantitative estimate of the hydroxylation rate. This study describes the validation of the procedure with some 21 studies performed on 15 subjects in different conditions. [7 alpha-3H]cholesterol was administered intravenously in 50 ml of plasma and thereafter blood was sampled at timed intervals for 4 to 5 days. The rate of the hydroxylation of cholesterol was calculated from the time course of the specific activities of plasma cholesterol and body water after tracer administration and was expressed as 7 alpha-hydroxycholesterol formed/24 hr. Calculated values of hydroxylation in three control subjects (493 +/- 206), five patients with hyperlipoproteinemia (539 +/- 168), and seven cirrhotic patients (153 +/- 136) are in good agreement with figures reported for bile acid synthesis determined with other techniques. Cholesterol 7 alpha-hydroxylation rate is reduced in patients with cirrhosis, the impairment being related to the severity of the disease. Cholestyramine administered to one subject for 4 weeks produced a threefold increase of the hydroxylation. Administration of chenodeoxycholic acid resulted in a 50% decrease, whereas that of ursodeoxycholic did not produce consistent changes of the hydroxylation rate. The results support the current view that 7 alpha-hydroxylation of cholesterol is rate-limiting in the synthesis of bile acids.(ABSTRACT TRUNCATED AT 250 WORDS
1985
- Effect of different bile acids on biliary secretion of Alkaline phosphatase in man
[Capitolo/Saggio]
P., Loria; PONZ DE LEON, Maurizio; F., Zironi; Bertolotti, Marco; D., Menozzi; N., Carulli
abstract
Not applicable
1984
- "In vivo" evaluation of 7-alpha-hydroxylation of cholesterol in man
[Articolo su rivista]
Bertolotti, Marco; F., Zironi; PONZ DE LEON, Maurizio; D., Menozzi; N., Carulli
abstract
Not applicable
1984
- Determinanti della secrezione biliare di colesterolo nell'uomo: ruolo della composizione del pool degli acidi biliari.
[Articolo su rivista]
Carulli, N; Loria, Paola; Bertolotti, Marco; PONZ DE LEON, Maurizio
abstract
Supplemento "Progressi nella epatologia italiana".
1984
- Determinants of bile lipid secretion: bile acid detergency
[Abstract in Atti di Convegno]
P., Loria; Bertolotti, Marco; I., Iori; PONZ DE LEON, Maurizio; G., Taddia; N., Carulli
abstract
Not applicable
1984
- Effect of thyroid function on hepatic sterol metabolism in man
[Abstract in Atti di Convegno]
P., Loria; PONZ DE LEON, Maurizio; Bertolotti, Marco; F., Zironi; R., Iori; N., Carulli
abstract
Not applicable
1984
- Effects of acute changes of bile acid pool composition on biliary lipid secretion
[Articolo su rivista]
Carulli, Nicola; Loria, Paola; Bertolotti, Marco; PONZ DE LEON, Maurizio; D., Menozzi; G., Medici; I., Piccagli
abstract
To elucidate the mechanism responsible for the bile acid-induced changes of biliary lipid secretion, we evaluated bile flow and biliary output of bile acids, cholesterol, phospholipids, and alkaline phosphatase activity in seven cholecystectomized subjects with a balloon occludable T-tube during two experimental periods: (a) depletion of the endogenous bile acid pool and (b) replacement of the pool by means of duodenal infusion with individual bile acids, such as deoxycholic (DCA), chenodeoxycholic (CDCA), cholic (CA), and ursodeoxycholic (UDCA) acids. Bile flow, cholesterol, and phospholipid output were linearly related to bile acid secretion in all experimental periods. During the replacement periods, the amount of cholesterol and phospholipids coupled to bile acids was significantly different (at 1% level at least) for each individual bile acid secreted; it was the highest during DCA secretion (slope value: 0.209 for cholesterol and 0.434 for phospholipids) followed, in the order, by CDCA (0.078 and 1.794), CA (0.044 and 0.127), and UDCA (0.030 and 0.122). The phospholipid to cholesterol ratio was higher during secretion of CA and UDCA as compared with DCA and CDCA. The secretion of CA seemed to stimulate a greater bile flow than the other bile acids did. The infusion of all bile acids, except UDCA, induced an increase of biliary alkaline phosphatase activity as compared with the values of the depletion period. The mean highest increase (13-fold the pretreatment value) was observed during DCA secretion followed by CDCA (fivefold) and CA (1.5-fold). These results would suggest that the physical chemical properties, namely the lipid-solubilizing capacity, of bile acids could directly contribute to the regulation of biliary lipid secretion. The observed changes in biliary alkaline phosphatase activity lend support to the view that bile acid-induced lipid secretion may be, at least in part, contributed by membrane solubilization.
1984
- Role of bile acid pool composition on biliary lipid secretion
[Capitolo/Saggio]
N., Carulli; P., Loria; Bertolotti, Marco; PONZ DE LEON, Maurizio; G., Medici; D., Menozzi; F., Zironi; R., Iori
abstract
Not applicable
1983
- Biliary secretion of alkalyne phosphatase (AP) in man: dependency on the bile acid (BA) secretion and detergency of BA pool
[Articolo su rivista]
P., Loria; PONZ DE LEON, Maurizio; F., Zironi; Bertolotti, Marco; D., Menozzi; N., Carulli
abstract
Not applicable
1983
- Determinanti della secrezione lipidica biliare nell'uomo: ruolo della composizione del pool degli acidi biliari
[Articolo su rivista]
N., Carulli; P., Loria; Bertolotti, Marco; PONZ DE LEON, Maurizio
abstract
Not applicable
1981
- Chenodeoxycholic acid metabolism in patients with thyroid dysfunction.
[Articolo su rivista]
Loria, Paola; Bertolotti, Marco; PONZ DE LEON, Maurizio; Iori, R; Carulli, N.
abstract
no abstract