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Lucia CARULLI

Professore Associato
Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze sede ex-Medicina, Endocrinologia, Metabolismo e Geriatria


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Pubblicazioni

2021 - Dynamic angiopoietin-2 assessment predicts survival and chronic course in hospitalized patients with COVID-19 [Articolo su rivista]
Villa, E.; Critelli, R.; Lasagni, S.; Melegari, A.; Curatolo, A.; Celsa, C.; Romagnoli, D.; Melegari, G.; Pivetti, A.; Di Marco, L.; Casari, F.; Arioli, D.; Turrini, F.; Zuccaro, V.; Cassaniti, I.; Riefolo, M.; de Santis, E.; Bernabucci, V.; Bianchini, M.; Lei, B.; de Maria, N.; Carulli, L.; Schepis, F.; Gozzi, C.; Malaguti, S.; Del Buono, M.; Brugioni, L.; Torricelli, P.; Trenti, T.; Pinelli, G.; Bertellini, E.; Bruno, R.; Camma, C.; D'Errico, A.
abstract

This study examined the association between dynamic angiopoietin-2 assessment and COVID-19 short- and long-term clinical course. We included consecutive hospitalized patients from 1 February to 31 May 2020 with laboratory-confirmed COVID-19 from 2 Italian tertiary referral centers (derivation cohort, n 5 187 patients; validation cohort, n 5 62 patients). Serum biomarker levels were measured by sandwich enzyme-linked immunosorbent assay. Lung tissue from 9 patients was stained for angiopoietin-2, Tie2, CD68, and CD34. Cox model was used to identify risk factors for mortality and nonresolving pulmonary condition. Area under the receiver operating characteristic curve (AUROC) was used to assess the accuracy of 3- and 10-day angiopoietin-2 for in-hospital mortality and nonresolving pulmonary condition, respectively. Three-day angiopoietin-2 increase of at least twofold from baseline was significantly associated with in-hospital mortality by multivariate analysis (hazard ratio [HR], 6.69; 95% confidence interval [CI], 1.85-24.19; P 5 .004) with AUROC 5 0.845 (95% CI, 0.725-0.940). Ten-day angiopoietin-2 of at least twofold from baseline was instead significantly associated with nonresolving pulmonary condition by multivariate analysis (HR, 5.33; 95% CI, 1.34-11.77; P # .0001) with AUROC 5 0.969 (95% CI, 0.919-1.000). Patients with persistent elevation of 10-day angiopoietin-2 levels showed severe reticular interstitial thickening and fibrous changes on follow-up computed tomography scans. Angiopoietin-2 and Tie2 were diffusely colocalized in small-vessel endothelia and alveolar new vessels and macrophages. Angiopoietin-2 course is strongly associated with COVID-19 in-hospital mortality and nonresolving pulmonary condition. Angiopoietin-2 may be an early and useful predictor of COVID-19 clinical course, and it could be a relevant part of disease pathogenesis. Angiopoietin-2 blockade may be a COVID-19 treatment option.


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 - 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.


2019 - Angiopoietin-2/Tie2 Inhibition by Regorafenib Associates With Striking Response in a Patient With Aggressive Hepatocellular Carcinoma [Articolo su rivista]
Todesca, P.; Marzi, L.; Critelli, R. M.; Cuffari, B.; Caporali, C.; Turco, L.; Pinelli, G.; Schepis, F.; Carulli, L.; de Maria, N.; Casari, F.; Scaglioni, R.; Villa, E.
abstract


2019 - Gender differences in chronic alcoholic and viral liver diseases [Articolo su rivista]
Carulli, L.; Romagnoli, D.; Turco, L.; Bernabucci, V.; Villa, E.
abstract

Chronic liver disease progresses in men and women at different rates, regardless of the etiology of the disease itself. In general, the natural history of chronic liver disease is more favorable in women than in men. The biological basis of these marked differences, in an organ that is not considered a classical hormone-dependent organ, is the presence in the liver of receptors both for estrogens and for androgens, which make the liver susceptible to changes in hormone levels during the various stages of reproductive life. In the literature, there are several studies that demon-strate, both in experimental animal models and in humans, that the presence of estrogens, at levels similar to those of the fertile period, is in principle protective against the develop-ment of a more severe disease, while on the contrary the effect of androgenic modulation has negative effects. Estrogen protection disappears when a woman goes into menopause. As estrogen levels decrease, the tendency to develop a more pronounced fibrosis increases. Most impor-tantly, there is a marked propensity to develop primary liver cancer, which in women over 65 has a similar incidence to that of men.


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 - 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 - 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


2019 - Retraction: The OMICs Window into Nonalcoholic Fatty Liver Disease (NAFLD) (Metabolites 2019, 9(2), 25) [Articolo su rivista]
Carulli, L.; Zanca, G.; Schepis, F.; Villa, E.
abstract

As the authors of the title paper [1], it is with great regret that we inform the readership of Metabolites that we have asked the journal’s publisher, MDPI, to retract the paper from the scientific literature. Due to human error, we included contents similar to article [2], which has already been published by Pirola et al. We apologize to the readership of Metabolites and to the authors of [2] for any inconvenience caused. MDPI is a member of the Committee on Publication Ethics (COPE) and takes the responsibility to enforce strict ethical policies and standards very seriously. To ensure the integrity of the publication record, [1] is retracted and shall be marked accordingly.


2019 - The OMICs window into nonalcoholic fatty liver disease (NAFLD) [Articolo su rivista]
Carulli, L.; Zanca, G.; Schepis, F.; Villa, E.
abstract

Nonalcoholic fatty liver disease (NAFLD) is a common cause of hepatic abnormalities worldwide. Nonalcoholic steatohepatitis (NASH) is part of the spectrum of NAFLD and leads to progressive liver disease, such as cirrhosis and hepatocellular carcinoma. In NASH patient, fibrosis represents the major predictor of liver-related mortality; therefore, it is important to have an early and accurate diagnosis of NASH. The current gold standard for the diagnosis of NASH is still liver biopsy. The development of biomarkers able to predict disease severity, prognosis, as well as response to therapy without the need for a biopsy is the focus of most up-to-date genomic, transcriptomic, proteomic, and metabolomic research. In the future, patients might be diagnosed and treated according to their molecular signatures. In this short review, we discuss how information from genomics, proteomics, and metabolomics contribute to the understanding of NAFLD pathogenesis.


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 - 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 - 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.


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 - 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 - 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 - 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.


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 - 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 - Telomere shortening as genetic risk factor of liver cirrhosis [Articolo su rivista]
Carulli, Lucia
abstract

Cirrhosis is the main complication of chronic liver disease, leads to progressive liver function impairment and is the main risk factor for the development of liver cancer. Liver failure at endstage cirrhosis is associated with increased mortality with liver transplantation as the only possible treatment at this stage. The pathogenesis of liver cirrhosis is not completely elucidated. Although the common factors leading to liver injury, such as viral hepatitis, alcohol consume or fatty liver disease can be identified in the majority of patients a small percentage of patients have no apparent risk factors. Moreover given the same risk factors, some patients progress to cirrhosis whereas others have a benign course, the reason remains unclear. In order to develop new diagnostic and therapeutic tools, it is s essential to understand the pathogenesis of cirrhosis. The identification of genetic risk factors associated with cirrhosis is one of the possible approach to achieve these goal. In the past years several studies have supported the role of telomere shortening and cirrhosis. In the recent year several studies on the relation between several single nucleotide polymorphism (SNPs) and cirrhosis have been published; it has been proposed also a cirrhosis risk score based on seven SNPs. Also epidemiological studies on identical twins and in different ethnic groups have been supporting the importance of the role of genetic risk factors. Finally in the very recent years it has been suggested that telomere shortening may represent a genetic risk factor for the development of cirrhosis.


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 - 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 - Telomere and telomerase in chronic liver disease and hepatocarcinoma [Articolo su rivista]
Carulli, Lucia; Anzivino, Claudia
abstract

The pathogenesis of liver cirrhosis is not completely elucidated. Although in the majority of patients, the risk factors may be identified in B and C viral hepatitis, alcohol intake, drugs or fatty liver disease, there is a small percentage of patients with no apparent risk factors. In addition, the evolution of chronic liver disease is highly heterogeneous from one patient to another. Among patient with identical risk factors, some rapidly progress to cirrhosis and hepatocellular carcinoma (HCC) whereas others have a benign course. Therefore, a genetic predisposition may contribute to the development of cirrhosis and HCC. Evidence supporting the role of genetic factors as a risk for cirrhosis has been accumulating during the past years. In addition to the results from epidemiological studies, polymorphisms studies and data on twins, the concept of telomere shortening as a genetic risk factor for chronic liver disease and HCC has been proposed. Here we review the literature on telomerase mutations, telomere shortening and liver disease including hepatocellular carcinoma.


2014 - Telomeres and atherosclerosis [Articolo su rivista]
Carulli, Lucia
abstract

Abstract The pathogenesis of atherosclerosis, an age-related disorder, may be due to a premature biological ageing. Cellular senescence, the finite replicative lifespan of cells, plays a critical role in the pathogenesis of atherosclerosis. The biological mechanism that triggers the onset of cellular senescence is thought to be telomere shortening. The two major mechanisms responsible for telomere shortening are the end-replication problem, oxidative DNA damage as well as inflammation induced by environmental risk factors. Repair of the endothelium depends on the presence of endothelial progenitor cells which depends on the hematopoietic stem cells (HSC) reserves. In numerous past studies, short LTL has been associated with atherosclerosis. Here we review the literature on telomere biology and coronary artery disease (CAD).


2014 - The Individual Care Plan (ICP): proposal of a model to improve the communication between hospital and primary health care services [Articolo su rivista]
Carulli, Lucia; Becchi, Maria Angela; Carozza, Lorenzo Mauro; Martucci, Gianfranco; Pignatti, Fabio
abstract

Background. Patients admitted to Internal Medicine wards are frequently defined complex patients for their severe symptoms, comorbidity, disabilities and socioeconomic critical conditions. Once the clinical stability is achieved, they may be discharged from hospital and to ensure continuity of care they require personalized arrangements providing medical, nursing and social supports in primary health care services. The aim of this study is to propose a model of Individual Care Plan (ICP) for complex patients. Methods. The model was developed starting from the assessment of multidimensional needs according to the International Classification of Functioning, Disability and Health (ICF) of World Health Organization (WHO), and defining for each detected need the goals, the related interventions, the professionals involved and the devices prescribed for personal use. Results. This paper presents the model in a practical manner, indicating the ICP of a complex patient. The ICP, divided into three sections (clinical, care and environmental) describes all the aspects of cure and care to be delivered in the primary health care services. Conclusions. The ICP that we proposed is a dynamic tool aimed to ensure the continuity of care and cure after hospital discharge, to facilitate the communication between hospital and primary health services and in the different settings of care in which the patient transits, to monitor the evolution of multidimensional needs over the time. Finally the ICP is useful in evaluating the costs, results and outcome of care and cure of a patient.


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 - Classical and innovative insulin sensitizing drugs for the prevention and treatment of NAFLD [Articolo su rivista]
Carulli, Lucia; Mauro, Maurantonio; Lionel, Hebbard; Baldelli, Enrica; Loria, Paola; George, Jacob
abstract

Background. Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disorder worldwide, comprises a spectrum of conditions ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. NASH is associated with an increased risk of hepatocellular carcinoma (HCC) and cardiometabolic disease. Insulin resistance (IR) is the underlying pathogenic mechanism for NAFLD, the presence of which in turn, is a strong predictor for the development of metabolic disorders. Hence, therapy of NAFLD with insulin-sensitizing drugs (ISDs) should ideally improve the key hepatic histological changes (steatosis, inflammation and fibrosis), but should also reduce cardiometabolic and cancer risk. Objectives. In this review, the rationale for the use of ISDs and the evidence for their efficacy are detailed. In particular, the mechanism of action, potential for use, limitations and untoward effects of metformin and thiazolidinediones are systematically reviewed. Further, we discuss novel ISDs that may have potential clinical utility in NAFLD. Results and Conclusion. Despite the theoretical prediction that ISDs might have beneficial effects on disease outcomes, evidence that ISDs are able to alter the natural history of NAFLD are presently not available. The exploration of novel strategies exploiting “non-conventional” ISDs is encouraged


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.


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 - 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 - Synchronous cryptogenic liver cirrhosis and idiopathic pulmonary fibrosis: a clue to telomeres involvement on line pubblication 03-Oct-2012Hepatology- [Articolo su rivista]
Carulli, Lucia; Dei Cas, A; Nascimbeni, Fabio
abstract

Background: Cryptogenic liver cirrhosis (CC) and Idiopathic pulmonary fibrosis (IPF) are chronic, progressive diseases with poor prognosis that share inflammation and fibrosis of target organs as common pathogenetic mechanisms. Both are included in the spectrum of syndrome of telomeres shortening. We describe a case of synchronous diagnosis of IPF and CC associated with a novel mutation in telomerase reverse transcriptase (hTERT). Subjects and Design: The proband was a 48-year-old active smoker, formerly obese, woman with type-2 diabetes mellitus. IPF and CC had a rapid and negative course. Her large family had an excess of type-2 diabetes and chronic liver disease and a high prevalence of different cancers, premature menopause and osteoporosis. In this family, we suggested an implication of telomeres shortening. Results: Sequencing and mutation analysis of hTERT and hTR demonstrated the presence of a novel hTERT mutation (L153M) and of a hTERT polymorphism (A305A). The patient was a carrier of both mutation and polymorphism, which were observed also in other family members. The relevance of L153M variant was confirmed by protein sequence alignment and by the prediction program PolyPhen. Furthermore, leukocyte telomeres length was significantly shorter in family members compared to age-matched healthy controls (0.94 ± 0.45 vs 1.37 ± 0.63; p=0.007). Conclusions: this is the first description of the coexistence of CC and IPF associated with a novel telomerase mutation not in the setting of dyskeratosis congenita. This case report gives further evidence of telomeres involvement in liver disease progression and suggests a possible link between NASH and CC through telomeres shortening.


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 - Ultrasonographic fatty liver indicator, a novel score which rules out NASH and is correlated with metabolic parameters in NAFLD. [Articolo su rivista]
Ballestri, Stefano; A., Lonardo; Romagnoli, Dante; Carulli, Lucia; L., Losi; Cp, Day; Loria, Paola
abstract

BACKGROUND: Differentiating steatosis from NASH is key in deciding treatment and follow-up schedules. We hypothesized that sonographic grading of steatosis willcorrelate with metabolic and pathologic changes of NASH.METHODS: Fifty-three non-consecutive patients had a semi-quantitative evaluation of hepatic steatosis through ultrasonographic Fatty Liver Indicator (US-FLI) justprior to liver biopsy. All biopsies demonstrated NAFLD. US-FLI is a new scoring system ranging 2-8 based on the intensity of liver/kidney contrast, posterior attenuation of ultrasound beam, vessel blurring, difficult visualization of gallbladder wall, difficult visualization of the diaphragm and areas of focalsparing. NAFLD is diagnosed by the minimum score ≥2. Ultrasonographic findings were correlated with metabolic and histological data. Inter-observer US-FLI scoreagreement, evaluated by three different operators in 31 consecutive patients with steatosis, showed "almost perfect/substantial" agreement (P < 0.001).RESULTS: US-FLI showed a positive correlation with HOMA, insulin, uric acid, ferritin, ALT and bilirubin and was associated with steatosis extent assessed histologically and histological features of NASH, except for fibrosis. US-FLI was an independent predictor of NASH (OR 2.236; P = 0.007) and a US-FLI < 4 had ahigh negative predictive value (94%) in ruling out the diagnosis of severe NASH according to Kleiner's criteria.CONCLUSION: Data confirm the hypothesis that US-FLI significantly correlates with metabolic derangements and individual pathologic criteria for NASH and may betterselect patients for liver biopsy.


2011 - Genetic determinants of susceptibility and severity in nonalcoholic fatty liver disease. [Articolo su rivista]
Daly, Ak; Ballestri, Stefano; Carulli, Lucia; Loria, Paola; Day, C. P.
abstract

Nonalcoholic fatty liver disease (NAFLD) in most patients involves only simple hepatic steatosis; however, a minority develop progressive steatohepatitis. Family studies and inter-ethnic differences in susceptibility suggest that genetic factors may be important risk determinants for progressive disease. Polymorphisms in genes affecting lipid metabolism, cytokines, fibrotic mediators and oxidative stress may be associated with steatohepatitis and/or fibrosis, but most of these findings require replication. A recent finding that a nonsynonymous polymorphism in the PNPLA3 gene predicts the extent of steatosis in NAFLD has been replicated in at least eight studies, with several studies also demonstrating an association with fibrosis. A new genome-wide association study has identified several additional novel associations with NAFLD severity. Other disease genes may be identified by similar approaches in the future.


2011 - Human Immunodeficiency Virus Is the Major Determinant of Steatosis and Hepatitis C Virus of Insulin Resistance in Virus-associated Fatty Liver Disease. [Articolo su rivista]
Guaraldi, Giovanni; Lonardo, A; Ballestri, Stefano; Zona, Stefano; Stentarelli, Chiara; Orlando, Gabriella; Carli, Federica; Carulli, Lucia; Roverato, A; Loria, Paola
abstract

BACKGROUND AND AIMS: To promote our understanding of the relative contribution of metabolic and viral factors, the independent predictors of fatty liver and insulin resistance (IR) were assessed by comparing patients with nonalcoholic fatty liver disease (NAFLD) to individuals with virus-associated fatty liver disease (VAFLD): human immunodeficiency virus (HIV)-VAFLD, hepatitis C virus (HCV)-VAFLD and HIV-HCV-VAFLD.METHODS: One hundred eighty eight consecutive patients with viral infections (103 HIV, 85 patients with HCV genotype 1 infection: 45 mono-infected and 40 HIV/HCV co-infected) with or without steatosis and 126 NAFLD patients were analyzed. Steatosis was diagnosed by ultrasonography. To assess the odds ratio (OR) of steatosis and IR, HCV and NAFLD, respectively, were used as the reference values. IR was evaluated through homeostasis model (HOMA) and the metabolic syndrome (MetS) using standard criteria.RESULTS: The prevalence of VAFLD was 47%. Multivariate logistic regression analysis was carried out using HCV as the reference. VAFLD was predicted by HIV, HIV/HCV, female gender, waist circumference (WC) and HOMA (OR = 3.99, 3.76, 2.80, 1.08 and 1.18). According to multiple linear regression using NAFLD as a reference, IR was predicted by HCV, HIV and HIV/HCV, WC, triglycerides (coefficient beta = 2.25, 0.99, 1.86, 0.08, 0.05, respectively). In linear models, for any given number of components of MetS, HCV and HCV/HIV-associated fatty liver disease had greater HOMA compared to NAFLD (p <0.001).CONCLUSIONS: Whereas HIV confers a higher risk of steatosis, VAFLD is associated with higher IR than NAFLD and such an effect is specifically linked to HCV rather than to HIV infection.


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 &gt; 65), compared to younger subjects (10239 vs 12662 microg/100 microg cholesterol; P &lt; 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.


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 &lt; 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 &lt; 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

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2009 - Antiretroviral drugs induced metabolic diseases in HIV infected patients. [Abstract in Atti di Convegno]
Guaraldi, Giovanni; A., Leonardo; S., Ballestri; Zona, Stefano; C., Stenterelli; Orlando, Gabriella; Carli, Federica; Carulli, Lucia; A., Roverato
abstract

The aim of the first study was to describe prevalence and predictors of HIV virus associated fatty liver disease that in HIV-infected HAART- experienced patients are unknown.The aim of the second study was to ascertain a) the determinants of steatosis and insulin resistance in virus-associated fatty liver disease and b) the role of HIV, HCV and HIV/HCV as modulators of the relationship between MS and IR.


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 - 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 - Fatty liver disease associated with epatiti C and/or human immunodeficiency virus: characterization of the link between hepatic steatosis, insulin resistance and metabolic syndrome. [Abstract in Rivista]
Guaraldi, Giovanni; A., Lonardo; S., Ballestri; S., Zona; C., Stentarelli; G., Orlando; F., Carli; Carulli, Lucia; A., Roverato; Loria, Paola
abstract

Little is known about the relationship between steatosis, insulin resistance (IR) and metabolic syndrome (MS) in patients with hepatitis C (HCV) and/or human immunodeficiency virus (HIV) infections. The aim of this study was to ascertain the determinants of steatosis and of insulin resistance in virus-associated fatty liver disease and the role of HIV, HCV and HIV/HCV as modulators of the relationship between MS and IR


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.


2009 - Hepatitis C virus-infected patients are 'spared' from the metabolic syndrome but not from insulin resistance. A comparative study of nonalcoholic fatty liver disease and hepatitis C virus-related steatosis. [Articolo su rivista]
Lonardo, A; Ballestri, Stefano; Adinolfi, Le; Violi, Enrico; Carulli, Lucia; Lombardini, S; Scaglioni, Federica; Ricchi, Matteo; Ruggiero, G; Loria, Paola
abstract

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis C feature steatosis and insulin resistance (IR), conditions associated with the metabolic syndrome (MS). OBJECTIVES: To assess the prevalence of MS and determinants of IR in patients with NAFLD and chronic hepatitis C. METHODS: Ninety-three consecutive patients with NAFLD, 97 with chronic hepatitis C virus (HCV) genotypes 1 and 2, and 182 'healthy' controls without steatosis were enrolled in the present study. The prevalence of MS was assessed by modified Adult Treatment Panel III criteria and IR by the homeostasis model assessment of insulin resistance (HOMA-IR). IR was defined as the 75th percentile of the HOMA-IR of control subjects. RESULTS: While the prevalence of IR was similar in NAFLD and HCV-infected subjects (70.0% and 78.7%, respectively), the prevalence of MS was significantly higher in NAFLD patients than in HCV-infected patients (27.9% versus 4.1%) and in controls (5.6%). With multivariate analysis, IR was predicted by body mass index (OR 1.263; 95% CI 1.078 to 1.480) and triglyceridemia (OR 1.011; 95% CI 1.002 to 1.020) in NAFLD and by sex (OR for female sex 0.297; 95% CI 0.094 to 0.940) and fibrosis stage (OR 2.751; 95% CI 1.417 to 5.340) in chronic hepatitis C. CONCLUSIONS: IR is independently associated with body mass index and triglyceridemia in NAFLD, sex and fibrosis in chronic HCV infection, and has a higher prevalence in NAFLD and chronic hepatitis C than in controls. However, the frequency of MS in HCVinfected patients, similar to that of controls, is significantly lower than that seen in NAFLD patients. The current diagnostic criteria of MS are more likely to 'capture' patients with NAFLD than with chronic hepatitis C, although both groups are insulin resistant


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 - 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 - Replica a: “Increased synthesis of bile acids in gallstone disease is a global finding and not a peculiar condition solely in Chile”, di M. Rudling. [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 - The neck-liver axis. Madelung disease as further evidence for an impact of body fat distribution on hepatic histology [Articolo su rivista]
Ballestri, Stefano; Amedeo, Lonardo; Carulli, Lucia; Matteo, Ricchi; Lorena, Bertozzi; DE SANTIS, Giorgio; Mario, Bondi; Loria, Paola
abstract

tissue.A 49-year-old alcoholic man withMD(Fig. 1) fulfilling ATP IIIcriteria6 for arterial hypertension, waist girth and HDL cholesterol,and showing bull-like neck due to subcutaneuos lipoma in DCA,quit drinking alcohol when first observed in 2001. Subsequently,the patient was subjected to anthropometric laboratory evaluationand paired liver biopsy. Owing to neurological and respiratorycomplications, surgical removal of 5kg adipose tissue from the neck area was performed at 2 times (2005-2007). Follow-up of this patient (June 2001– June 2007) disclosed increasing body weight (90-148 kg) coupled with decreasing triglyceride serum levels (90-38mg/dL), as if the expanded adipose tissue were avidly absorbingcirculating triglycerides, thus removing them from the bloodstream.Paired liver biopsy showedalcoholic steatohepatitis in advanced fibrotic stage (2001) and precirrhoticchanges without steatosis (2006), as seen in NAFLD.studies support,therefore, hepatic steatosis to be a protective mechanism against freefatty acid toxicity in the liver. Conversely, selective accumulation offateb in the neck-DCA could be a risk factor for inflammatoryfibrotichepatic changes.


2008 - Tipologia dei ricoveri negli Ospedali Universitari: l'impatto sulle attività istituzionali [Articolo su rivista]
Carulli, Nicola; S., Rondinella; Carulli, Lucia; O., Caiti; M., Pescetelli; Becchi, Maria Angela
abstract

Lo studio riporta le caratteristiche di pazienti ricoverati in Reparti di Universitari di Medicina Interna. Vengono riportati i profili sanitari e socio-assistenziali dei pazienti ricoverati, gli aspetti relativi al ricovero e alla dimissione e viene focalizzata l'attenzione sulle "dimissioni difficili" e sui fattori ad esse correlati. Viene discusso l'impatto di questi aspetti sulla formazione e la ricerca e viene delineato il ruolo della Medicina Interna in un modello innovativo di servizio accademico orientato alla formazione


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 - Cirrosi criptogenetiche. Un report di 5 pazienti [Abstract in Rivista]
Giannico, I; Scaglioni, F; Carulli, Lucia; Lonardo, A; Maurantonio, M; Bonati, Me; Iori, R; Loria, Paola; Carulli, Nicola
abstract

La cirrosi criptogenetica si associa prevalentemente a sesso femminile, età media 64 anni, sovrappeso/ obesità e diabete di tipo 2 , questo porta a definire la cirrosi criptogenetica come cirrosi metabolica.


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 - 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.


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 - 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 - Does fatty liver associate with carotid atherosclerosis? [Abstract in Rivista]
Scaglioni, F; Lombardini, S; Ricchi, M; Verrone, A; Ballestri, S; Carulli, Lucia; Lonardo, A; Carulli, Nicola; Loria, Paola
abstract

age rahter than fatty liver is a predictor of atherosclerosis and is also teh only independent predictor of CVD in patients with non alcoholic fatty liver.


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 - Gender, fatty liver and GGT [Articolo su rivista]
Carulli, Lucia; Lonardo, A; Lombardini, Silvia; Marchesini, G; Loria, Paola
abstract

Letter


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 - Hepatic steatosis and insulin resistance: Does etiology make a difference? [Articolo su rivista]
A., Lonardo; S., Lombardini; F., Scaglioni; Carulli, Lucia; M., Ricchi; D., Ganazzi; Le, Adinolfi; G., Ruggiero; N., Carulli; P., Loria
abstract

Background/Aims: To ascertain whether the etiology of hepatic steatosis modulates insulin resistance (IR) and to determine the predictors of IR. Methods: We studied IR through HOMA IR in 146 subjects, 99 of whom had ultrasonographic and/or histologic steatosis. Twenty-two had familial heterozygous hypobetalipoproteinemia (FHBL), 48 had non-alcoholic fatty liver disease (NAFLD), 34 HCV infection (17 with HCV1b, 17 with HCV3a) and 42 were healthy controls without steatosis. Results: Steatosis was present in 77.3% of FHBL and, by enrolment criteria, in all NAFLD and HCV cases. Overall HOMA-IR correlated with BMI and GGT (P < 0.01). FHBL and healthy groups had similar HOMA-IR and GGT values, whereas higher levels were observed in HCV and NAFLD. HCV3a and FHBL patients were hypolipidemic. HONIA-IR was similar in FHBL patients and controls and lower than in HCV and NAFLD. FHBL patients had a high extent of steatosis, similar to that observed in HCV3a, but lower grading and staging than NAFLD and HCV. At multivariate analysis, steatosis and GGT predicted HOMA-IR. Conclusions: Data suggest that not all hepatic fat associates with IR. FHBL patients, for some aspects, resemble HCV3a infection, possibly suggesting a shared steatogenic mechanism. Among steatotic patients serum GGT levels is the independent predictor of IR. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.


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 - 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.


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: diabetes, genetics and ethnicity [Articolo su rivista]
Carulli, Lucia; S., Rondinella; S., Lombardini; I., Canedi; Loria, Paola; Carulli, Nicola
abstract

The prevalence of insulin resistance and diabetes has increased in the past decades at an alarming rate in all Western countries and in those countries which are adopting a 'western life style'. This trend suggests the impact of environmental factors such as diet, obesity and physical activity on the pathogenesis of diabetes. However it is known that the prevalence and variation of prevalence, as consequence of environmental changes, it is different in various ethnic groups. Studies conducted in multiethnic populations suggest that some ethnic groups, such as Hispanics or Asian Indians, might have a particular predisposition, possibly on genetic basis, to develop insulin resistance and diabetes, when exposed to adverse conditions. According to the 'thrifty gene' hypothesis, a clustering of different genetic defects or polymorphisms, developed as genetic advantage in some populations, could predispose some ethnic groups to insulin resistance and diabetes in presence of an increased food supply. Multiple mutations, associated with small changes in insulin sensitivity, when combined, may induce a significant reduction in insulin sensitivity. This review deals with the possible relevance of genetic factors in the expression of insulin resistance and diabetes in relation to ethnicity.


2005 - Review article: the metabolic syndrome and non-alcoholic fatty liver disease [Articolo su rivista]
Loria, Paola; A., Lonardo; Carulli, Lucia; Am, Verrone; Ricchi, Matteo; S., Lombardini; A., Rudilosso; Ballestri, Stefano; Carulli, Nicola
abstract

Metabolic syndrome represents a common risk factor for premature cardiovascular disease and cancer whose core cluster includes diabetes, hypertension, dyslipidaemia and obesity. The liver is a target organ in metabolic syndrome patients in which it manifests itself with nonalcoholic fatty liver disease spanning steatosis through hepatocellular carcinoma via steatohepatitis and cirrhosis. Given that metabolic syndrome and non-alcoholic fatty liver disease affect the same insulin-resistant patients. not unexpectedly, there are amazing similarities between metabolic syndrome and non-alcoholic fatty liver disease in terms of prevalence, pathogenesis, clinical features and outcome. The available drug weaponry for metabolic syndrome includes aspirin, metformin, peroxisome proliferator-activated receptor agonists, statins, ACE (angiotensin I-converting enzyme) inhibitors and sartans, which are potentially or clinically useful also to the non-alcoholic fatty liver disease patient. Studies are needed to highlight the grey areas in this topic. Issues to be addressed include: diagnostic criteria for metabolic syndrome; nomenclature of non-alcoholic fatty liver disease; enlargement of the clinical spectrum and characterization of the prognosis of insulin resistance-related diseases: evaluation of the most specific clinical predictors of metabolic syndrome/non-alcoholic fatty liver disease and assessment of their variability over the time; characterization of the importance of new risk factors for metabolic syndrome with regard to the development and progression of non-alcoholic fatty liver disease.


2004 - Cholestatic icterus: is there still a role for the clinic? [Articolo su rivista]
Mauro, Maurantonio; Leonardo, Venezia; Carulli, Lucia; Silvia, Lombardini; Chiara, Gabbi; Mario De, Santis; Gabriele, Luppi; Giampiero, Rigo; Carulli, Nicola
abstract

Caso clinico. Ruolo della clinica e delle indagini strumentali nella diagnosi diferenziale della colestasi epatica.


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 &lt; 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 &lt; 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&lt; 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 - Epidemiologia e storia naturale dell'epatopatia steatosica non alcolica [Articolo su rivista]
Loria, Paola; Lonardo, A; Lombardini, S; Leonardi, F; Carulli, Lucia; Ganazzi, D; Rudilosso, A; Verrone, Am; Ricchi, M; Carulli, Nicola
abstract

Epidemiology of NAFLD is not well defined. Estimated prevalence in teh general population is 20% for NAFLD and 2% for NASH. the disease affects all ages, males are more affected than females . Associated conditions are obeisty ,type 2 diabetes , hyperlypemia, all features of metabolic syndroem. Natural history includes a clinically nenign course for steatosis and teh progression of nASH to cirrhosis in a significant proportion of cases(20%) and eventually to hepatocellular carcinoma.. steatosis is a negative predictor for graft surbvival in orthotopic liver transplantation and is associated with the progression of hepatitis C virus to cirrhosis.


2003 - Genetic polymorphism PC-1 K121Q and ethnic susceptibility to insulin resistance. [Articolo su rivista]
Abate, N; Carulli, Lucia; CABO CHAN A., Jr; Chandalia, M; Snell, Pg; Grundy, S. M.
abstract

Genetic susceptibility may be responsible for high prevalence of insulin resistance in Asian Indians. This study was carried out in samples of local Asian Indians and Caucasians to determine whether plasma cell membrane glycoprotein (PC)-1 K121Q and insulin receptor substrate-1 (IRS-1) G972A polymorphisms contribute significantly to susceptibility to insulin resistance in Asian Indians. The frequency of carrying at least one copy of the PC-1 121Q variant in Asian Indians was significantly higher than that in Caucasians (P = 0.01), but the frequency was similar for IRS-1 972A (6% and 7%). A significantly higher insulin area under the curve during oral glucose tolerance testing (P < 0.0001) and lower insulin sensitivity during hyperinsulinemic-euglycemic clamps (P = 0.04) were found in Asian Indians with PC-1 121Q variant compared with Asian Indians with wild-type PC-1 and with Caucasians with or without the polymorphism. IRS-1 972A was not associated with any change in insulin sensitivity. We conclude that the PC-1 K121Q polymorphism associates with primary insulin resistance in migrant Asian Indians. A relatively high frequency of this polymorphism thus may be one factor contributing to insulin resistance susceptibility in Asian Indians. This finding indicates the need for expanded studies on the association between PC-1 K121Q and insulin resistance in a representative sample of the Asian Indian population.


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 - 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 - Sindromi steatosiche non alcoliche. Stato dell'arte e progressi nella ricerca. [Articolo su rivista]
Loria, P.; Lonardo, A.; Lombardini, S.; Leonardi, F.; Carulli, Lucia; Borsatti, A.; Verrone, A. M.; Canedi, I.; Ricchi, M.; Ganazzi, D.; Bagni, A.; Bertolottti, M.; Rudilosso, A.; D`amico, R.; Neri, P.; Pulvirenti, M.; De Micheli, E.; Carulli, Nicola
abstract

review della letteratura su sindromi steatosiche


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 - Interethnic diffrences in Free Fatty acids and glucose metabolism in asian Indians and Caucasinas [Abstract in Rivista]
Caochan, A; Chandalia, M; Carulli, Lucia; Grundy, Sm; Abate, N.
abstract

Mild increase in body fat content is known to induce excessive insulin resistance in Asian Indians compared to Caucasians. We evaluated the difference in Free fatty acids and Glucose metabolism in Asian Indians and Caucasians. Insulin-dependent plasma FFA suppression is impaired in Asian Indians with even minor body fat content compared to Caucasians. Furthermore , induced plasma FFA elevation had much more impact on insulinmediated glucose disposal of Asian Indians than Caucasians even in very thin and insulin sensitive subjetcs.


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 - 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 - 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 - Regulation of ob gene expression: evidence for epinephrine-induced suppression in human obesity [Articolo su rivista]
Carulli, Lucia; Ferrari, S; Bertolini, M; Tagliafico, Enrico; DEL RIO, Graziano
abstract

Leptin acts as satiety factor and increases energy expenditure. Studies conducted on animals and in vitro on adipocytes culture have shown that infusion of catecholamines leads to a significant reduction of ob gene expression; it appears of interest to evaluate the in vivo effects of adrenergic activation on the expression of the ob gene in humans. We studied ob gene expression in adipose tissue samples from 13 obese subjects before and after epinephrine (25 ng/min x kg ideal body weight for 3 h) and 6 obese patients during saline infusion. Hormonal infusion led to a significant increase in epinephrine plasma levels (from 27 +/- 4 to 339 +/- 75 pg/mL; P < 0.001), plasma free fatty acids (from 0.73 +/- 0.05 to 0.98 +/- 0.07; P < 0.05), heart rate (13.5 +/- 3.1 beats/min; F = 2.9; P < 0.03), and systolic blood pressure (F = 2.7; P < 0.05), whereas diastolic blood pressure did not show significant variation. Plasma leptin levels decreased by the end of the infusion (from 63 +/- 13 to 49 +/- 11 ng/mL; P < 0.05), and ob messenger ribonucleic acid levels were significantly reduced (decrease amounting to 47 +/- 5% of basal values). Our study shows that adrenergic activation contributes to regulate ob messenger ribonucleic acid levels in humans. The interaction between epinephrine and leptin may operate during metabolic and psychological stress to regulate energy expenditure and food intake.