Predicting the occurrence of embolic events: an analysis of 1456 episodes of infective endocarditis from the Italian Study on Endocarditis (SEI)

Background: Embolic events are a major cause of morbidity and mortality in patients with infective endocarditis. We analyzed the database of the prospective cohort study SEI in order to identify factors associated with the occurrence of embolic events and to develop a scoring system for the assessment of the risk of embolism. Methods: We retrospectively analyzed 1456 episodes of infective endocarditis from the multicenter study SEI. Predictors of embolism were identified. Risk factors identified at multivariate analysis as predictive of embolism in left-sided endocarditis, were used for the development of a risk score: 1 point was assigned to each risk factor (total risk score range: minimum 0 points; maximum 2 points). Three categories were defined by the score: low (0 points), intermediate (1 point), or high risk (2 points); the probability of embolic events per risk category was calculated for each day on treatment (day 0 through day 30).Results: There were 499 episodes of infective endocarditis (34%) that were complicated by 65 1 embolic event. Most embolic events occurred early in the clinical course (first week of therapy: 15.5 episodes per 1000 patient days; second week: 3.7 episodes per 1000 patient days). In the total cohort, the factors associated with the occurrence of embolism at multivariate analysis were prosthetic valve localization (odds ratio, 1.84), right-sided endocarditis (odds ratio, 3.93), Staphylococcus aureus etiology (odds ratio, 2.23) and vegetation size 65 13 mm (odds ratio, 1.86). In left-sided endocarditis, Staphylococcus aureus etiology (odds ratio, 2.1) and vegetation size 65 13 mm (odds ratio, 2.1) were independently associated with embolic events; the 30-day cumulative incidence of embolism varied with risk score category (low risk, 12%; intermediate risk, 25%; high risk, 38%; p < 0.001).Conclusions: Staphylococcus aureus etiology and vegetation size are associated with an increased risk of embolism. In left-sided endocarditis, a simple scoring system, which combines etiology and vegetation size with time on antimicrobials, might contribute to a better assessment of the risk of embolism, and to a more individualized analysis of indications and contraindications for early surgery

Lipid Accumulation in Hearts Transplanted From Nondiabetic Donors to Diabetic Recipients

Background: Early pathogenesis of diabetic cardiomyopathy (DMCM) may involve lipotoxicity of cardiomyocytes in the context of hyperglycemia. There are many preclinical studies of DMCM pathogenesis, but the human evidence is still poorly understood. Objectives: By using a nondiabetic mellitus (non-DM) heart transplanted (HTX) in diabetes mellitus (DM) recipients, this study conducted a serial study of human heart transplant recipients evaluating cardiac effects of diabetic milieu (hyperglycemia and insulin resistance) on lipotoxic-mediated injury. We evaluated cardiomyocyte morpho-pathology by seriated biopsies of healthy implanted hearts in DM recipients during 12-month follow-up from HTX. Because metformin reduces ectopic lipid accumulation, we evaluated the effects of the drug in a nonrandomized subgroup. Methods: The DMCM-AHEAD (Diabetes and Lipid Accumulation and Heart Transplant) prospective ongoing study (NCT03546062) evaluated 158 first HTX recipients (82 non-DM, 76 DM of whom 35 [46%] were receiving metformin). HTX recipients were undergoing clinical standard evaluation (metabolic status, echocardiography, coronary computed tomography angiography, and endomyocardial biopsies). Biopsies evaluated immune response, Oil Red-O staining, ceramide, and triacylglycerol levels. Lipotoxic factors and insulin resistance were evaluated by reverse transcriptase–polymerase chain reaction. Results: There was a significant early and progressive cardiomyocyte lipid accumulation in DM but not in non-DM recipients (p = 0.019). In the subgroup receiving metformin, independently from immunosuppressive therapy that was similar among groups, lipid accumulation was reduced in comparison with DM recipients not receiving the drug (hazard ratio: 6.597; 95% confidence interval: 2.516 to 17.296; p &lt; 0.001). Accordingly, lipotoxic factors were increased in DM versus non-DM recipients, and, relevantly, metformin use was associated with fewer lipotoxic factors. Conclusions: Early pathogenesis of human DMCM started with cardiomyocyte lipid accumulation following HTX in DM recipients. Metformin use was associated with reduced lipid accumulation independently of immunosuppressive therapy. This may constitute a novel target for therapy of DMCM

Lipid Accumulation in Hearts Transplanted From Nondiabetic Donors to Diabetic Recipients

Background: Early pathogenesis of diabetic cardiomyopathy (DMCM) may involve lipotoxicity of cardiomyocytes in the context of hyperglycemia. There are many preclinical studies of DMCM pathogenesis, but the human evidence is still poorly understood. Objectives: By using a nondiabetic mellitus (non-DM) heart transplanted (HTX) in diabetes mellitus (DM) recipients, this study conducted a serial study of human heart transplant recipients evaluating cardiac effects of diabetic milieu (hyperglycemia and insulin resistance) on lipotoxic-mediated injury. We evaluated cardiomyocyte morpho-pathology by seriated biopsies of healthy implanted hearts in DM recipients during 12-month follow-up from HTX. Because metformin reduces ectopic lipid accumulation, we evaluated the effects of the drug in a nonrandomized subgroup. Methods: The DMCM-AHEAD (Diabetes and Lipid Accumulation and Heart Transplant) prospective ongoing study (NCT03546062) evaluated 158 first HTX recipients (82 non-DM, 76 DM of whom 35 [46%] were receiving metformin). HTX recipients were undergoing clinical standard evaluation (metabolic status, echocardiography, coronary computed tomography angiography, and endomyocardial biopsies). Biopsies evaluated immune response, Oil Red-O staining, ceramide, and triacylglycerol levels. Lipotoxic factors and insulin resistance were evaluated by reverse transcriptase–polymerase chain reaction. Results: There was a significant early and progressive cardiomyocyte lipid accumulation in DM but not in non-DM recipients (p = 0.019). In the subgroup receiving metformin, independently from immunosuppressive therapy that was similar among groups, lipid accumulation was reduced in comparison with DM recipients not receiving the drug (hazard ratio: 6.597; 95% confidence interval: 2.516 to 17.296; p < 0.001). Accordingly, lipotoxic factors were increased in DM versus non-DM recipients, and, relevantly, metformin use was associated with fewer lipotoxic factors. Conclusions: Early pathogenesis of human DMCM started with cardiomyocyte lipid accumulation following HTX in DM recipients. Metformin use was associated with reduced lipid accumulation independently of immunosuppressive therapy. This may constitute a novel target for therapy of DMCM

Violenza contro le donne. Uno studio interdisciplinare

La violenza maschile contro le donne non \ue8 una novit\ue0 degli ultimi anni, emersa grazie alla recente adozione di convenzioni che ne attestano il carattere strutturale. Non siamo dinanzi a una congiunturae neppure a un fenomeno emergenziale. Lo scopo del volume, che documenta gli esiti di una prima International Summer School dedicata alla violenza contro le donne, \ue8 offrire un\u2019analisi multifocale del carattere sistemico che le violazioni subite dalle donne hanno ormai assunto, il pi\uf9 delle volte al di l\ue0 dei luoghi di appartenenza e della condizione sociale. I saggi che compongono l\u2019opera esplorano in ottica interdisciplinare da un lato il terreno simbolico, linguistico e rappresentativo che alimenta la violenza maschile contro le donne, dall\u2019altro l\u2019efficacia degli strumenti adottati dalla politica e dal diritto per contrastarla

Questioni LGBTI e dimensione del pubblico

I saggi contenuti nel volume si occupano di unioni omosessuali, surrogacy, transessualismo e intersessualit\ue0, questioni uscite negli ultimi tempi dall\u2019ombra e dalla rimozione ed entrate in uno spazio di dibattito politico. La visibilit\ue0 associata alla luce dell\u2019emersione pubblica sposta i confini di territori fisici e simbolici che il diritto contribuisce convenzionalmente e transitoriamente a tracciare di volta in volta. Lo studio \ue8 l\u2019esito di intense giornate di lavoro e confronto accademico, ospitate all\u2019interno di una International Summer School in Gender Studies, che hanno idealmente rappresentato un luogo pubblico di appaesamento delle questioni di genere e segnatamente di quelle LGBTI, acronimo che va col tempo arricchendosi e con il quale si indica, senza esaurirlo, un ventaglio di possibilit\ue0 che la dimensione affettiva, relazionale, sessuale, identitaria pu\uf2 esprimere. I saggi fanno luce su cambiamenti in atto, su dibattiti, anche nominali e lessicali, senza censurare il fatto che pregiudizi e stereotipi nell\u2019et\ue0 dei diritti possono assumere mute inedite e subdole

Le nuove frontiere del diritto e della politica. Studi e questioni LGBTI

I saggi contenuti in questo volume si occupano di unioni omosessuali, surrogacy, transessualismo e intersessualit\ue0, questioni uscite negli ultimi tempi dall\u2019ombra e dalla rimozione ed entrate in uno spazio di dibattito politico. La visibilit\ue0 associata alla luce dell\u2019emersione pubblica sposta i confini di territori fisici e simbolici che il diritto contribuisce convenzionalmente e transitoriamente a tracciare di volta in volta. Questo studio \ue8 l\u2019esito di intense giornate di lavoro e confronto accademico, ospitate all\u2019interno di una International Summer School in Gender Studies, che hanno idealmente rappresentato un luogo pubblico di appaesamento delle questioni di genere e segnatamente di quelle LGBTI, acronimo che va col tempo arricchendosi e con il quale si indica, senza esaurirlo, un ventaglio di possibilit\ue0 che la dimensione affettiva, relazionale, sessuale, identitaria pu\uf2 esprimere. Questi saggi cercano di fare luce su cambiamenti in atto, su dibattiti, anche nominali e lessicali, senza censurare il fatto che pregiudizi e stereotipi nell\u2019et\ue0 dei diritti possono assumere mute inedite e subdole

Genere e religioni. Un dialogo interdisciplinare

Il volume \ue8 il risultato di due giornate seminariali organizzate nel 2017 e 2018 presso l\u2019Universit\ue0 degli Studi di Macerata che hanno messo a tema le differenze di genere e di religioni, attraverso uno sguardo multidisciplinare e transdisciplinare. I diversi contributi spaziano dalla filosofia alla medicina, dall\u2019antropologia alla politica, dalla storia alla sociologia e alla teologia, in un intreccio di prospettive accomunate da un interesse di ricerca che si addensa attorno al genere come domanda posta alle mentalit\ue0 e tradizioni religiose. Contributi di Francesca Bartolacci, Edoardo Bressan, Carla Canullo, Carla Carotenuto, Antonio Chiaese, Ines Corti, Martina Crescenti, Isabella Crespi, Elisabetta Croci Angelini, Maria Luisa Dupuis, Simona Epasto, Claudio Giovannini, Roberto Lambertini, Cinzia La Rocca, Walter Malorni, Natascia Mattucci, Serena Noceti, Maria Teresa Pagano, Donatella Pagliacci, Sabina Pavone, Amanda Rosini, Mina Sedhev, Daniela Verducci, Maria Letizia Zanier