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101. Upstream therapy with statin and recurrence of atrial fibrillation after electrical cardioversion. Review of the literature and meta-analysis

Author

Loffredo Lorenzo, Angelico Francesco, Perri Ludovica, and Violi Francesco

Subjects
Atrial fibrillation, Statin, Electrical cardioversion, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Background Atrial fibrillation (AF) is the most common sustained arrhythmia observed in clinical practice. Electrical cardioversion (EC) is commonly used to restore and maintain sinus rhythm but it is characterized by high rate of recurrences. Several trials analyzed the effects of statins to reduce the recurrences in AF with contradictory results. Methods We performed a meta-analysis of the interventional trials with statins in patients with persistent AF to evaluate recurrences after EC. Only randomized controlled trials were included in the analysis. Data sources included: Medline, ISI Web of Science, SCOPUS and Cochrane database (up to June 2012). Data extraction was performed by three authors. Study-specific odds ratios (ORs) were combined using fixed-effects model. Results Six studies with 515 patients were included in the analysis. Statins used in the selected trials were: atorvastatin (at dosages ranging from 10 to 80 mg/day), pravastatin (40 mg/day) and rosuvastatin (20 mg/day). AF recurrence after EC occurred in 108/258 (41.8%) of patients treated with statins and in 132/257 (51.3%) patients not on treatment with statins. Compared with control, recurrences were significantly reduced with statin treatment (O.R.: 0.662; 95% C.I., 0.45-0.96; p=0.03); statin treatment was associated with an absolute risk reduction of 0.095 and a number needed to treat of 11. Conclusions This review suggests that statin therapy was significantly associated with a decreased risk of recurrence in patients with persistent AF after EC.

Published
2012
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102. Oxidative stress mediated arterial dysfunction in patients with obstructive sleep apnoea and the effect of continuous positive airway pressure treatment

Author

Del Ben Maria, Fabiani Mario, Loffredo Lorenzo, Polimeni Licia, Carnevale Roberto, Baratta Francesco, Brunori Marco, Albanese Fabiana, Augelletti Teresa, Violi Francesco, and Angelico Francesco

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Abstract Background Several studies suggest an increase of oxidative stress and a reduction of endothelial function in obstructive sleep apnoea syndrome (OSAS). We assessed the association between OSAS, endothelial dysfunction and oxidative stress. Further aim was to evaluate the effect of nasal continuous positive airway pressure (nCPAP) on oxidative stress and arterial dysfunction. Methods We studied 138 consecutive patients with heavy snoring and possible OSAS. Patients underwent unattended overnight home polysomnography. Ten patients with severe OSAS were revaluated after 6 months of nCPAP therapy. To assess oxidative stress in vivo, we measured urinary 8-iso-PGF2α and serum levels of soluble NOX2-derived peptide (sNOX2-dp). Serum levels of nitrite/nitrate (NOx) were also determined. Flow-mediated brachial artery dilation (FMD) was measured to asses endothelial function. Results Patients with severe OSAS had higher urinary 8-iso-PGF2α (p Conclusions The results of our study indicate that patients with OSAS and cardiometabolic comorbidities have increased oxidative stress and arterial dysfunction that are partially reversed by nCPAP treatment.

Published
2012
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103. Carotid plaque detection improves the predictve value of CHA2DS2-VASc score in patients with non-valvular atrial fibrilation: The ARAPACIS Study

Author

Basili, Stefania, Loffredo, Lorenzo, Pastori, Daniele, Proieti, Marco, Farcomeni, Alessio, Vesti, Anna Rta, Pignatelli, Pasquale, Davì, Giovanni, Hiatt, William R., Lip, Gregory Y. H., Corazza, Gino R., Perticone, Francesco, Violi, Francesco, 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., Battaglia, G., Atzori, S., Delitala, G., Angelucci, E., Sestili, S., Traisci, G., De Feudis, L., Di Michèle, 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., 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., Belfiäore, 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., 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., 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., Prisco, D., Marcucci, R., Ferro, D., Cangemi, R., Perri, L., Polimeni, L., Catasca, E., Vicario, T., Russo, R., Saliola, M., Del Ben, M., Ange-lico, F., Calvieri, C., Bucci, T., Baratta, F., Migliacci, R., Porciello, G., Corrao, S., Pignataro, F. S., Napoleone, L., Talerico, G., Amoroso, D., Romiti, G. F., Ruscio, E., Toriello, F., Todisco, T., Di Tanna, G., Saccheti, M. L., Puddu, P. E., Anzaldi, M., Bazzini, C., Bianchi, P. I., Boari, B., Bracco, G., Buonauro, A., Butta, C., Buzzetti, E., Calabria, S., Capeci, W., Caradio, F., Carleo, P., Carrabba, M. D., Castorani, L., Cecchetto, L., Cicco, S., Cimini, C., Colombo, B. M., De Giorgi, A., De Vuono, S., Del Corso, L., Denegri, A., Di Giosia, P., Durante Mangoni, E., Falsetti, L., Forgione, A., Giorgini, P., Grassi, D., Grembiale, A., Hijazi, D., Iamele, L., Lorusso, G., Marchese, A., Marra, A. M., Masala, M., Miceli, G., Montebianco Abenavoli, L., Murgia, G., Naccarato, P., Pattoneri, P., Perego, F., Pesce, P., Piano, S., Pinna, M., Pinto, D., Pretti, V., Pucci, G., Raparelli, V., Salinaro, F., Salzano, A., Santilli, F., Scarpini, F., Scicali, R., Sirico, D., Suppressa, P., Talia, M., Tassone, E. J., Torres, D., Vazzana, N., Vecchio, C. R., Vidili, G., Vitale, F., Zaccone, V., Simi Young Internists GIS Group, Basili, S, Loffredo, L, Pastori, D, Proieti, M, Farcomeni, A, Vesti, A, Pignatelli, P, Davi, G, Hiatt, W, Lip, G, Corazza, G, 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, 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, Iannuzi, A, Bresciani, A, Giunta, R, Utili, R, Iorio, V, Adinolfi, L, 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, 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, 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, Pasqualini, L, Oliverio, G, Pende, A, Aitom, N, Ricchio, R, Fimognari, F, Alletto, M, Messina, S, Sesti, G, Arturi, F, Fiorentino, T, Pedace, E, Scarpino, P, Carullo, G, Maio, R, Sciacqua, A, Frugiuele, P, 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, 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, Annoni, G, Bruni, A, Castagna, A, Spinelli, D, Miceli, E, Paduia, D, Schinco, G, Spreafico, S, Secchi, B, Vanoli, M, Casella, G, Pulixi, E, Sansone, L, Serra, M, 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, Scozzari, F, Muiesan, M, 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, 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, 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, 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, Prisco, D, Marcucci, R, Ferro, D, Cangemi, R, Perri, L, Polimeni, L, Catasca, E, Vicario, T, Russo, R, Saliola, M, Del Ben, M, Ange-lico, F, Calvieri, C, Bucci, T, Baratta, F, Migliacci, R, Porciello, G, Corrao, S, Pignataro, F, Napoleone, L, Talerico, G, Amoroso, D, Romiti, G, Ruscio, E, Toriello, F, Todisco, T, Di Tanna, G, Saccheti, M, Puddu, P, Anzaldi, M, Bazzini, C, Bianchi, P, Boari, B, Bracco, G, Buonauro, A, Butta, C, Buzzetti, E, Calabria, S, Capeci, W, Caradio, F, Carleo, P, Carrabba, M, Castorani, L, Cecchetto, L, Cicco, S, Cimini, C, Colombo, B, De Giorgi, A, De Vuono, S, Del Corso, L, Denegri, A, Di Giosia, P, Durante Mangoni, E, Falsetti, L, Forgione, A, Giorgini, P, Grassi, D, Grembiale, A, Hijazi, D, Iamele, L, Lorusso, G, Marchese, A, Marra, A, Masala, M, Miceli, G, Montebianco Abenavoli, L, Murgia, G, Naccarato, P, Pattoneri, P, Perego, F, Pesce, P, Piano, S, Pinna, M, Pinto, D, Pretti, V, Pucci, G, Raparelli, V, Salinaro, F, Salzano, A, Santilli, F, Scarpini, F, Scicali, R, Sirico, D, Suppressa, P, Talia, M, Tassone, E, Torres, D, Vazzana, N, Vecchio, C, Vidili, G, Vitale, F, Zaccone, V, 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., 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., 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., Prisco, D., Marcucci, R., Ferro, D., Cangemi, R., Perri, L., Polimeni, L., Catasca, E., Vicario, T., Russo, R., Saliola, M., Del Ben, M., Ange-lico, F., Calvieri, C., Bucci, T., Baratta, F., Migliacci, R., Porciello, G., Corrao, S., Pignataro, F. S., Napoleone, L., Talerico, G., Amoroso, D., Romiti, G. F., Ruscio, E., Toriello, F., Todisco, T., Di Tanna, G., Saccheti, M. L., Puddu, P. E., Anzaldi, M., Bazzini, C., Bianchi, P. I., Boari, B., Bracco, G., Buonauro, A., Butta, C., Buzzetti, E., Calabria, S., Capeci, W., Caradio, F., Carleo, P., Carrabba, M. D., Castorani, L., Cecchetto, L., Cicco, S., Cimini, C., Colombo, B. M., De Giorgi, A., De Vuono, S., Del Corso, L., Denegri, A., Di Giosia, P., Durante Mangoni, E., Falsetti, L., Forgione, A., Giorgini, P., Grassi, D., Grembiale, A., Hijazi, D., Iamele, L., Lorusso, G., Marchese, A., Marra, A. M., Masala, M., Miceli, G., Montebianco Abenavoli, L., Murgia, G., Naccarato, P., Pattoneri, P., Perego, F., Pesce, P., Piano, S., Pinna, M., Pinto, D., Pretti, V., Pucci, G., Raparelli, V., Salinaro, F., Salzano, A., Santilli, F., Scarpini, F., Scicali, R., Sirico, D., Suppressa, P., Talia, M., Tassone, E. J., Torres, D., Vazzana, N., Vecchio, C. R., Vidili, G., Vitale, F., Zaccone, V., 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., 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., 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., Prisco D., Marcucci R., Ferro D., Cangemi R., Perri L., Polimeni L., Catasca E., Vicario T., Russo R., Saliola M., Del Ben M., Ange-lico F., Calvieri C., Bucci T., Baratta F., Migliacci R., Porciello G., Corrao S., Pignataro F.S., Napoleone L., Talerico G., Amoroso D., Romiti G.F., Ruscio E., Toriello F., Todisco T., Di Tanna G., Saccheti M.L., Puddu P.E., Anzaldi M., Bazzini C., Bianchi P.I., Boari B., Bracco G., Buonauro A., Butta C., Buzzetti E., Calabria S., Capeci W., Caradio F., Carleo P., Carrabba M.D., Castorani L., Cecchetto L., Cicco S., Cimini C., Colombo B.M., De Giorgi A., De Vuono S., Del Corso L., Denegri A., Di Giosia P., Durante Mangoni E., Falsetti L., Forgione A., Giorgini P., Grassi D., Grembiale A., Hijazi D., Iamele L., Lorusso G., Marchese A., Marra A.M., Masala M., Miceli G., Montebianco Abenavoli L., Murgia G., Naccarato P., Pattoneri P., Perego F., Pesce P., Piano S., Pinna M., Pinto D., Pretti V., Pucci G., Raparelli V., Salinaro F., Salzano A., Santilli F., Scarpini F., Scicali R., Sirico D., Suppressa P., Talia M., Tassone E.J., Torres D., Vazzana N., Vecchio C.R., Vidili G., Vitale F., and Zaccone V.

Subjects
Atherosclerosis, Atrial fibrillation, Carotid plaque, CHA2DS2-VASc score, Stroke, Vascular disease, Carotid Artery Diseases, Male, Atherosclerosis, Atrial fibrillation, Carotid plaque, CHA2DS2-VASc score, Stroke, Vascular disease, Aged, Aged, 80 and over, Ankle Brachial Index, Atrial Fibrillation, Female, Humans, Incidence, Italy, Plaque, Atherosclerotic, Retrospective Studies, Risk Factors, Survival Rate, Ultrasonography, Doppler, Risk Assessment, Cardiology and Cardiovascular Medicine, 030204 cardiovascular system & hematology, atrialf fibrillation, 0302 clinical medicine, Retrospective Studie, Carotid artery disease, CHA, 2, DS, VASc score, 80 and over, 030212 general & internal medicine, Myocardial infarction, CHA(2)DS(2)-VASc score, CHA 2 DS 2 -VASc score, Plaque, Atherosclerotic, Ultrasonography, Doppler, Atherosclerosi, Cardiology, artherosclerosis, atrial fibrillation, carotid plaque, stroke, vascular disease, aged, aged, 80 and over, ankle brachial index, carotid artery diseases, female, humans, incidence, italy, male, plaque, atherosclerotic, retrospective studies, risk factors, survival rate, ultrasonography, doppler, risk assessment, cardiology and cardiovascular medicine, Settore SECS-S/01 - Statistica, Human, medicine.medical_specialty, Socio-culturale, 03 medical and health sciences, Internal medicine, medicine, cardiovascular diseases, Risk factor, Survival rate, Carotid Artery Disease, business.industry, Risk Factor, medicine.disease, CHA2DS2–VASc score, business
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 CHA 2 DS 2 -VASc score. We investigated if systemic atherosclerosis as detected by ultrasound carotid plaque (CP) could improve the predictive value of the CHA 2 DS 2 -VASc score. Methods We analysed data from the ARAPACIS study, an observational study including 2027 Italian patients 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% patients. Adding CP to the VD definition leaded to higher VD prevalence (30.9%). During a median [IQR] follow-up time of 36months, 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 36months (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 predictive value of CHA 2 DS 2 -VASc score for stroke.

Published
2017

104. Under-prescription of statins in patients with non-alcoholic fatty liver disease

Author

M. Del Ben, Francesco Violi, Lorenzo Loffredo, Maurizio Averna, Daniele Pastori, Francesco Baratta, Licia Polimeni, Francesco Angelico, Del Ben, M., Baratta, F., Polimeni, L., Pastori, D., Loffredo, L., Averna, M., Violi, F., and Angelico, F.

Subjects
Male, Settore MED/09 - Medicina Interna, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), Disease, 030204 cardiovascular system & hematology, Endocrinology, 0302 clinical medicine, Drug Prescription, Non-alcoholic Fatty Liver Disease, Risk Factors, Cardiovascular Disease, Nutrition and Dietetic, Practice Patterns, Physicians', Nutrition and Dietetics, medicine.diagnostic_test, Fatty liver, Middle Aged, Diabetes and Metabolism, Cardiovascular Diseases, Practice Guidelines as Topic, Cohort, Under-prescription, Female, lipids (amino acids, peptides, and proteins), 030211 gastroenterology & hepatology, Guideline Adherence, Cardiology and Cardiovascular Medicine, Human, Adult, Cardiovascular risk, Non-alcoholic fatty liver disease, Statins, medicine.medical_specialty, Statin, medicine.drug_class, Context (language use), Health Services Misuse, Drug Prescriptions, 03 medical and health sciences, Internal medicine, medicine, Humans, Medical prescription, Aged, Dyslipidemias, Cross-Sectional Studie, business.industry, Risk Factor, nutritional and metabolic diseases, Non alcoholic, Biomarker, Cholesterol, LDL, medicine.disease, Cross-Sectional Studies, Dyslipidemia, Physical therapy, Hydroxymethylglutaryl-CoA Reductase Inhibitor, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Lipid profile, business, Biomarkers
Abstract

Background and Aim Non-alcoholic fatty liver disease (NAFLD) is a common disease associated with high cardiovascular risk. Management of dyslipidaemia plays a pivotal role in the prevention of CV events and statins have proved to be safe in these patients. However, in everyday clinical practice statin prescription is sometimes limited because of the concern of physicians about side-effects. The aim of the study was to investigate if the presence of NAFLD affects the prescription of lipid-lowering treatment in a large series of patients with cardio-metabolic disorders. Methods and Results Cardiovascular risk and LDL-C targets were defined according to ESC/EAS Guidelines in 605 consecutive adult subjects referred for screening of suspected metabolic diseases. Liver steatosis was assessed by ultrasound Hamaguchi criteria. In the whole cohort, 442 patients had indication for cholesterol-lowering treatment. Lack of statin prescription was present in 230 (52.0%) patients. Of these, 77 (33.5%) were very high-risk, 48 (20.8%) high-risk, and 105 (45.6%) moderate risk patients. Only 44% of the NAFLD patients with indication for statin treatment were on therapy. NAFLD patients on statin treatment had significantly lower ALT values as compared to those not on treatment (p Conclusions Our findings show that about 50% of patients with indication to statin treatment do not receive any cholesterol-lowering medication. Statin under-use was particularly high in subjects with NAFLD. Use of statin treatment should be encouraged in the context of NAFLD, as it may improve lipid profile and reduce the cardiovascular risk in this setting.

Published
2017
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105. Premature coronary disease in systemic lupus.

Author

Wurzel J, Goldman BI, Doria A, Shoenfeld Y, Pauletto P, Violi F, Loffredo L, Ferro D, Pezzetta F, Mascitelli L, Noël B, Roman MJ, Lockshin MD, Salmon JE, Stein CM, and Hahn BH

Published
2004

106. Low Rate of Intrahospital Deep Venous Thrombosis in Acutely Ill Medical Patients: Results From the AURELIO Study

Author

Marco Antonio Casciaro, Veronica Pacetti, Sciaila Bernardini, Francesco Violi, Sara Melis, Emilia Donnarumma, Sarah Lunardi, Andrea Crociani, Ludovica Pesci, Ilaria Maria Palumbo, Antonella Tufano, Maria Luna Summa, Stefania Basili, Lohengrin Stefania Pirillo, Lorenzo Baldini, Mauro Cacciafesta, Simona Battaglia, Chiara Cogliati, Corrado Lodigiani, Evaristo Ettorre, Pier Luigi Meloni, Maria Boddi, Giulia Pacciani, Ludovica Perri, Rosella Di Giulio, Alberto Vegetti, Alessio Farcomeni, Deborah Blanca, Lorenzo Loffredo, Elisabetta Rossi, Angela Sciacqua, Pasquale Pignatelli, Francesco Casella, Assunta Sauchella, Gianpaolo Vidili, Francesco Perticone, Domenico Ferro, Giovanni Di Minno, Rossella Rovereto, Maurizio Cringoli, Antonello Pietrangelo, Arianna Pannunzio, Maria Berria, Vincenzo Arienti, Loffredo, L., Arienti, V., Vidili, G., Cogliati, C., Battaglia, S., Perri, L., Di Giulio, R., Bernardini, S., Summa, M. L., Sciacqua, A., Perticone, F., Boddi, M., Di Minno, G., Lodigiani, C., Pietrangelo, A., Farcomeni, A., Violi, F., Basili, S., Pignatelli, P., Ferro, D., Rossi, E., Casciaro, M. A., Pirillo, L. S., Palumbo, I. M., Pannunzio, A., Pesci, L., Baldini, L., Meloni, P. L., Sauchella, A., Melis, S., Berria, M., Cringoli, M., Blanca, D., Casella, F., Ettorre, E., Cacciafesta, M., Vegetti, A., Crociani, A., Donnarumma, E., Pacciani, G., Rovereto, R., Lunardi, S., Tufano, A., and Pacetti, V.

Subjects
Male, medicine.drug_class, Low molecular weight heparin, Asymptomatic, Hospitals, University, Risk Factors, Secondary Prevention, Medicine, Humans, Cumulative incidence, Prospective Studies, Ultrasonography, Doppler, Color, Prospective cohort study, Aged, Aged, 80 and over, Venous Thrombosis, business.industry, Incidence (epidemiology), Incidence, Medicine (all), Acute Disease, Anticoagulants, Female, Follow-Up Studies, Italy, Length of Stay, Lower Extremity, General Medicine, medicine.disease, Pneumonia, Venous thrombosis, Respiratory failure, Anesthesia, medicine.symptom, business, Settore SECS-S/01 - Statistica
Abstract

Objective To evaluate the effect of hospitalization on deep venous thrombosis (DVT) rate by the cumulative incidence of DVT in the proximal venous tract of the lower limbs at admission and discharge. Methods The AURELIO (rAte of venoUs thRombosis in acutEly iLl patIents hOspitalized in internal medicine wards) multicenter observational study was carried out in hospital-university internal medicine wards including consecutive acutely ill medical patients. Patients underwent compression ultrasonography (CUS) of proximal lower limb veins at admission and discharge. The occurrence of DVT was the primary end point of the study. Results Among 1340 patients, 26 (1.9%; 95% CI, 1.3%-2.8%) had asymptomatic DVT at admission and were excluded. During the follow-up, 144 patients were excluded because of hospitalization less than 5 days. The remaining 1170 patients underwent a CUS at discharge. Two hundred fifty (21%) underwent prophylaxis with parenteral anticoagulants; the remaining 920 (79%) were not treated with anticoagulants. The mean length of hospitalization was 13±8 days. Compared with patients without prophylaxis, those treated with parenteral anticoagulants had a higher incidence of active cancer, heart and respiratory failure, pneumonia, renal failure, previous venous thromboembolism, reduced mobility, and elderly age. During the hospital stay, 3 patients with a negative CUS at admission experienced DVT in the proximal tract (0.025%, rate of 1 per 5017 patient-days); 2 of them were in prophylaxis with parenteral anticoagulants. Conclusion We provide evidence that in the real world acutely ill medical patients display more than 90% (1.9%) asymptomatic DVT at admission, whereas the intrahospital DVT occurrence is very low. This suggests a novel diagnostic workup and a careful reanalysis of anticoagulant prophylaxis.

Published
2019

107. Moderate alcohol use and health: a consensus document

Author

Simona Costanzo, M. Bucci, Lorenzo Loffredo, Claudio Pelucchi, Francesco Marangoni, Andrea Poli, Giuseppe Marelli, L. Lucchin, Francesco Visioli, Francesco Violi, C. La Vecchia, Alberico L. Catapano, M. Musicco, R. Sterzi, G. de Gaetano, Lucia Fontana, Roberto Vettor, Claudio Cricelli, G. Forlani, Carlo Nozzoli, Francesco Fattirolli, S. Frattini, Salvatore Minisola, Salvatore Novo, Ludovica Perri, Gianvincenzo Barba, Angelo Avogaro, L. Lazzaretto, Filippo Pieralli, A. Di Castelnuovo, Damiano Rizzoni, Rosalba Giacco, Stefano Bellentani, Walter Marrocco, Pompilio Faggiano, R. Cambieri, Poli, A, Marangoni, F, Avogaro, A, Barba, G, Bellentani, S, Bucci, M, Cambieri, R, Catapano, AL, Costanzo, S, Cricelli, C, de Gaetano, G, Di Castelnuovo, A, Faggiano, P, Fattirolli, F, Fontana, L, Forlani, G, Frattini, S, Giacco, R, La Vecchia, C, Lazzaretto, L, Loffredo, L, Lucchin, L, Marelli, G, Marrocco, W, Minisola, S, Musicco, M, Novo, S, Nozzoli, C, Pelucchi, C, Perri, L, Pieralli, F, Rizzoni, D, Sterzi, R, Vettor, R, Violi, F, Visioli, F, A. Poli, F. Marangoni, A. Avogaro, G. Barba, S. Bellentani, M. Bucci, R. Cambieri, A.L. Catapano, S. Costanzo, C. Cricelli, G. de Gaetano, A. Di Castelnuovo, P. Faggiano, F. Fattirolli, L. Fontana, G. Forlani, S. Frattini, R. Giacco, C. La Vecchia, L. Lazzaretto, L. Loffredo, L. Lucchin, G. Marelli, W. Marrocco, S. Minisola, M. Musicco, S. Novo, C. Nozzoli, C. Pelucchi, L. Perri, F. Pieralli, D. Rizzoni, R. Sterzi, R. Vettor, F. Violi, and F. Visioli

Subjects
Polyphenol, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, MEDLINE, Medicine (miscellaneous), Cognitive decline, Disease, Diabete, alcohol, cancer, cardiovascular disease, cognitive decline, diabetes, metabolic syndrome, overall mortality, polyphenols, prevention, ALCOHOLIC LIVER DISEASE, Breast cancer, Diabetes mellitus, Intervention (counseling), medicine, Overall mortality, Psychiatry, Cancer, Nutrition and Dietetics, business.industry, Prevention, Primary care physician, medicine.disease, Moderation, Cardiovascular disease, Metabolic syndrome, Settore MED/11 - Malattie Dell'Apparato Cardiovascolare, HEALTH, Cardiology and Cardiovascular Medicine, business, Alcohol, Polyphenols, Diabetes
Abstract

Aims The aim of this consensus paper is to review the available evidence on the association between moderate alcohol use, health and disease and to provide a working document to the scientific and health professional communities. Data synthesis In healthy adults and in the elderly, spontaneous consumption of alcoholic beverages within 30 g ethanol/d for men and 15 g/d for women is to be considered acceptable and do not deserve intervention by the primary care physician or the health professional in charge. Patients with increased risk for specific diseases, for example, women with familiar history of breast cancer, or subjects with familiar history of early cardiovascular disease, or cardiovascular patients should discuss with their physician their drinking habits. No abstainer should be advised to drink for health reasons. Alcohol use must be discouraged in specific physiological or personal situations or in selected age classes (children and adolescents, pregnant and lactating women and recovering alcoholics). Moreover, the possible interactions between alcohol and acute or chronic drug use must be discussed with the primary care physician. Conclusions The choice to consume alcohol should be based on individual considerations, taking into account the influence on health and diet, the risk of alcoholism and abuse, the effect on behaviour and other factors that may vary with age and lifestyle. Moderation in drinking and development of an associated lifestyle culture should be fostered.

Published
2013
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108. Does NADPH Oxidase Deficiency Cause Artery Dilatation in Humans?

Author

Anna Rosa Soresina, Valerio Sanguigni, Domenico De Mattia, Baldassarre Martire, Silvana Martino, Roberto Carnevale, Pasquale Pignatelli, Giuliana Giardino, Claudio Pignata, Paolo Rossi, Francesco Martino, Alessandro Plebani, Lorenzo Loffredo, Francesco Violi, Eleonora Gambineri, Maria Cristina Pietrogrande, Andrea Finocchi, Loffredo, L., Carnevale, R., Sanguigni, V., Plebani, A., Rossi, P., Pignata, Claudio, De Mattia, D., Finocchi, A., Martire, B., Pietrogrande, M. C., Martino, S., Gambineri, E., Giardino, Giuliana, Soresina, Ar, Martino, F., Pignatelli, P., and Violi, F.

Subjects
Male, Pathology, Physiology, Clinical Biochemistry, Vasodilation, isoprostane, NADPH Oxidase, atherosclerosis, NADPH oxidase, chronic granulomatous disease, Isoprostanes, medicine.disease_cause, Granulomatous Disease, Chronic, Biochemistry, Gastroenterology, Carotid Intima-Media Thickness, Chronic granulomatous disease, Chronic, Child, General Environmental Science, Membrane Glycoproteins, biology, artery, Young Adult, Humans, Carotid Arteries, Blood Platelets, Case-Control Studies, Adolescent, Female, medicine.anatomical_structure, NADPH Oxidase 2, cardiovascular system, Granulomatous Disease, hormones, hormone substitutes, and hormone antagonists, circulatory and respiratory physiology, Artery, medicine.medical_specialty, Urinary system, NADPH, Internal medicine, medicine, NADPH Oxidases, Molecular Biology, Settore MED/38 - Pediatria Generale e Specialistica, urogenital system, business.industry, Case-control study, Cell Biology, medicine.disease, biology.protein, General Earth and Planetary Sciences, business, Oxidative stress
Abstract

NADPH oxidase is known to modulate the arterial tone, but the role of its specific subunits is still unclear. The objective of this study was to compare the role of p47 and gp91phox (NOX2) on artery dilatation. We conducted a multicenter study enrolling 30 patients with chronic granulomatous disease (CGD) (25 with NOX2 deficiency and 5 with p47(phox) deficiency) and 30 healthy subjects (HS), matched for gender and age, in whom flow-mediated dilation (FMD), serum activity of NOX2 (soluble NOX2-derived peptide [sNOX2-dp]), urinary isoprostanes (8-iso-PGF2α), and platelet production of isoprostanes and NOX2 were determined. Compared to HS, patients with CGD had significantly higher FMD and lower sNOX2-dp and 8-iso-PGF2α levels. Compared to patients with NOX2 deficiency and HS, patients with p47(phox) hereditary deficiency had intermediate FMD and oxidative stress, that is, higher and lower FMD and lower and higher isoprostanes compared to HS and patients with NOX2 deficiency, respectively. In agreement with this finding, an ex vivo study showed higher inhibition of NOX2 activity and lower isoprostane formation in platelets from patients with NOX2 deficiency compared to platelets from ones with p47(phox) deficiency. Our observations lead to the hypothesis that oxidants are implicated in artery vasoconstriction.

Published
2013

109. Prevalence of peripheral artery disease by abnormal ankle-brachial index in atrial fibrillation: implications for risk and therapy

Author

Violi, Francesco, Daví, Giovanni, Hiatt, William, Lip, Gregory Y. H., Corazza, Gino R., Perticone, Francesco, Proietti, Marco, Pignatelli, Pasquale, Vestri, Anna R., Basili, Stefania, Desideri, ARAPACIS Study Investigators Alessandri Cesare (Dipartimento di Scienze e Biotecnologie Medico-Chirurgiche, G., Sapienza-Università di Roma), Serviddio Gaetano (Department of Medical and Surgical Sciences, University of Foggia), Fascetti Stefano (UOC Medicina Generale, USL 12 Viareggio, Toscana), Serra, Pietro, Palange Paolo(UOC Medicina Interna, I, Dipartimento di Sanità Pubblica, e Malattie Infettive, Greco, Eleonora, Bruno Graziella (Medicina, 3, Department of Medical Sciences, Città della Salute e della Scienza, A. O., University of Turin), Averna, Maurizio, Giammanco Antonina (Dipartimento Biomedico di Medicina Interna, e Specialistica (DIBIMIS), Università di Palermo), Sposito Pietro (Azienda Ospedaliera Ospedali Riuniti Papardo Piemonte, Messina), De Cristofaro Raimondo, De Gennaro Leonardo(Istituto di Medicina Interna, e Geriatria, Centro Emostasi, e Trombosi, Gemelli, Policlinico A., Roma), Loria, Paola, Pellegrini Elisa(Medicina Interna ad Indirizzo Metabolico, – NOCSAE Baggiovara, Department of Internal Medicine, Endocrinology, Metabolism and Geriatrics, Università degli Studi di Modena, e Reggio Emilia), Cominacini, Luciano, Mozzini Chiara (Dipartimento di Medicina, Sezione di Medicina Interna, D, Università di Verona), Sprovieri, Mario, Spagnuolo Vitaliano (UOC Medicina d'Urgenza, e PS, Stabilimento Ospedaliero dell'Annunziata, Cosenza), Cerqua Giannantonio (UOC Medicina Interna per l'Urgenza, S Giovanni Addolorata, Ao, Cerasola Giovanni, Mulé Giuseppe (Università degli Studi di Palermo), Barbagallo, Mario, Lo Sciuto Salvatore, Monteverde Alfredo(UOC di Geriatria, e Lungodegenza, Azienda Ospedaliera Universitaria Policlinico, Aoup, Palermo), Saitta, Antonino, Lo Gullo Alberto (UOC Medicina Interna, Università di Messina), Malatino, Lorenzo, Cilia Chiara (Clinica Medica, Ospedale, Cannizzaro, Università degli Studi di Catania), Licata, Giuseppe, Tuttolomondo, Antonino, Conigliaro Roberta (UOC Medicina Interna, e Cardioangiologia, Dipartimento Biomedico di Medicina Interna, e Specialistica, Università degli Studi di Palermo), Pinto, Antonio, Di Raimondo Domenico (UOC Medicina Vascolare, Dipartimento Biomedico di Medicina Interna e Specialistica, (Di. Bi. M. I. S. )., Signorelli, Santo, Anzaldi Massimiliano (Dipartimento di Medicina Interna, e Patologia, Università degli studi di Catania), De Palma Daniela, Galderisi, Maurizio, Cudemo Giuseppe (Dipartimento di Medicina Clinica, e Sperimentale, AUP Federico II di Napoli), Galletti, Ferruccio, Fazio Valeria(Dipartimento di Medicina Clinica, e Chirurgia, Università di Napoli Federico II), De Luca Nicola, Meccariello Alfonso (Centro Ipertensione, AUO Federico II, Napoli), Caputo, Dario, De Donato Maria Teresa (UO Medicina Interna, Azienda Ospedaliera Universitaria San Giovanni di Dio, e Ruggi D'Aragona, Salerno), Iannuzi, Arcangelo, Bresciani Alessandro (Divisione di Medicina Interna, Cardarelli, Osp. A., Giunta, Riccardo, Cimini Claudia (V Divisione Medicina Interna ed Immunoallergologia, Policlinico, Sun, Utili, Riccardo, Durante Mangoni Emanuele, Agrusta Federica (Medicina Infettivologica, e dei Trapianti, Monaldi, Ao, Sun, Napoli), Adinolfi Luigi, E., Sellitto, Cristiana, Restivo Luciano (Medicina Interna, Seconda Università di Napoli, Ospedale di Marcianise), Bellis, Paolo, Tirelli Paolo (UOC Medicina Interna e di Urgenza, e Pronto Soccorso, del Loreto Nuovo, P. O. S. M., Loreto, Mare), Sacerdoti, David, Pesce Paola (Clinica Medica, 5, Dipartimento di Medicina DIMED, Università degli Studi di Padova), Vanni Dino (UO Medicina Interna Arezzo, Ospedale San Donato, Azienda USL, 8 Arezzo), Iuliano, Luigi, Ciacciarelli, Marco, Pacelli Antonio (Department of Medico-Surgical Sciences and Biotechnology, Vascular Biology, Mass Spectrometry Lab, Sapienza-University of Rome), Palazzuoli Alberto (Sezione Cardiologia, Dipartimento di Medicina Interna, e Malattie Metaboliche, Università di Siena, Ospedale Le Scotte), Cacciafesta, Mauro, Gueli Nicola (UOC di Medicina Geriatrica, e Riabilitazione, Sapienza- Università di Roma, Capeci, William, Tarquinio, Nicola, Pellegrini Francesco (UO Medicina 'SS Benvenuto, e Rocco', Dipartimento di Medicina Interna, Asur, Marche, Area Vasta, n. 2., ex ZT 7), Vincentelli Giovanni Maria (UOS Breve Osservazione, Calibita 'Fatebenefratelli' Isola Tiberina, Ospedale S. G., Ravallese, Ferdinando, Santini Claudio (UOC Medicina Interna, Ospedale, Vannini, Letizia, Claudio, Petramala, Luigi, Zinnamosca Laura (UOD Ipertensione Secondaria, Dipartimento di Medicina Interna, e Specialità Mediche, Cilli, Mirella, Savoriti Claudio (UOC Medicina Interna F, e Malattie Metaboliche Dell'osso-Direttore Minisola Salvatore, Falaschi, Paolo, Martocchia, Antonio, Stefanelli Manuela (UO Geriatria, Andrea, Azienda Ospedaliera S., Facoltà di Medicina, e Psicologia, Marigliano, Vincenzo, Lo Iacono Cristina, Brusco Simona (Centro di Ricerca Interdipartimentale Scienze dell’Invecchiamento, Bertazzoni, Giuliano, Attalla El Halabieh Elias (UOC Medicina d’Urgenza, Dipartimento di Emergenza ed Accettazione, Paradiso, Michele, Lizzi Eugenio Maria, Timmi Stefano (Ospedale San Giovanni Battista, Ordine di Malta, Battisti Paola (Medicina Interna II, Ospedale San Giovanni-Addolorata, Cerci Sabina (UOC Medicina Interna, Ospedali Riuniti Frascati, Marino), Ciavolella Massimo (UOC Cardiologia-UTIC, Ospedale di Frascati, Di Veroli Claudio (Centro dell’Ipertensione Arteriosa e delle Malattie Metaboliche, e Renali, Casa di Cura 'San Domenico', Malci, Francesco, De Ciocchis Anita (UOC di Medicina Interna, Ospedale, ASL Roma, G, Subiaco), Abate, Damiano(Az., Castellino, Pietro, Curto, Irene, Vecchio Claudia (UOC Medicina Interna, Dipartimento di Scienze Mediche, e Pediatriche, Mannarino, Elmo, Pasqualini, Leonella, Fattori Chiara (Medicina Interna, Angiologia, e Malattie da Arteriosclerosi, Università degli Studi di Perugia), Pende, Aldo, Denegri, Andre, Artom Nathan (Clinica di Medicina Interna, 1, Università di Genova, San Martino - IST, IRCCS Az. Osp. Univ., Genova), Ricchio, Roberto, Fimognari Filippo Luca (UOC Geriatria, Azienda Ospedaliera di Cosenza, Alletto, Maurizio, Messina Simona (Unità Operativa di Medicina, Elia, Ospedale S., Caltanissetta), Sesti, Giorgio, Arturi, Franco, Grembiale Alessandro (Università degli Studi, UOC Medicina Interna, Policlinico Universitario 'Mater Domini'), Scarpino Paola Elisa, Carullo Giuseppe (Cattedra di Medicina Interna, UO Malattie Cardiovascolari, Campus Universitario di Germaneto, Università Magna Graecia di Catanzaro), Frugiuele, Pierluigi, Spagnuolo Vitaliano (UOC Medicina Interna, e Reumatologia, Stabilimento Ospedaliero Annunziata, Azienda Ospedaliera Cosenza), Battaglia Giuseppe (UO Lungodegenza, Serra San Bruno, S. O., ASP Vibo Valentia), Vidili, Gianpaolo, Atzori, Sebastiana, Delitala Giuseppe (Clinica Medica, Dipartimento di Medicina Clinica, e Sperimentale, Aou, Sassari), Davì, Giovanni, Angelucci, Ermanno, Sestili Simona (UOC di Clinica Medica, PO Clinicizzato di Chieti), Traisci, Giancarlo, De Feudis Lucrezia (UOC Medicina Interna, 2, PO di Pescara), Di Michele Dario, Fava Alessandra (UOC Medicina Interna, Asl, Teramo), Balsano, Clara, De Ciantis Pierpaolo (Dipartimento di Medicina Interna, e Sanità Pubblica, Università, dell'Aquila), Desideri, Giovambattista, Camerota Antonio (UOC Geriatria, e Lungodegenza Geriatrica, Dipartimento Medico ORM, Avezzano), Po, Migliacci, Rino, Medicina Interna, Porciello Giovanni (S. C., Ospedale della Valdichiana, Cortona, Usl, 8 Arezzo), Mezzetti Matteo (UOC Medicina Interna Ospedale del Casentino-Direttore Dr. Emilio Santoro, AUSL8 Arezzo), Gresele, Paolo, Vedovati, Cristina, Fierro Tiziana (Dipartimento di Medicina Interna, Sezione di Medicina Interna, e Cardiovascolare, Università di Perugia), Puccetti, Luca, Scarpini Francesca (Centro Aterosclerosi, Trombosi, e Coagulopatie, Università degli Studi di Siena, Azienda Ospedaliero-Universitaria Senese), Bertolotti, Marco, Mussi Chiara (UO Geriatria, Università degli Studi di Modena e Reggio Emilia), Dipartimento Integrato di Medicina Endocrinologia Metabolismo e Geriatria., Boddi, Maria, Savino, Andrea, Contri Silvia (Dipartimento di Area Critica Medico- Chirurgica, Università degli Studi di Firenze), Saller, Alois, Fabris Fabrizio (Clinica Medica1, Medicina Interna CLOPD, Departement of Medicine DIMED, University of Padova, Italy), Pesavento, Raffaele, Filippi, Lucia, Vedovetto Valentina (Dipartimento di Scienze Cardiologiche, Toraciche, e Vascolari, Clinica Medica, 2, Azienda Ospedaliera-Università di Padova), Puato Massimo (Clinica Medica IV, Dipartimento di Medicina, Azienda Ospedaliera Universitaria Padova, Padova), Fabris, Fabrizio, Treleani Martina (UOA Medicina, Policlinico, Universitario, Maselli, Monica, Corradin Maria Luisa, Giantin Valter (Clinica Geriatrica, Università di Padova), Semplicini Andrea (Medicina Interna, 1, Giovanni e Paolo, Ospedale SS., Venezia), Minuz, Pietro, Calabria, Stefano, Romano Simone (Sezione di Medicina Interna, C, Università di Verona, Aoui, Verona), Fantin, Francesco, Manica Angela (Dipartimento di Medicina, Sezione di Geriatria, Stockner, Ingrid, Pattis, Peter, Wiedermann), Gutmann Bernhard (Divisione di Medicina Interna-Direttore Prof. J., Ospedale centrale di Bolzano), Catena, Cristiana, Colussi GianLuca (Hypertension Unit and Division of Internal Medicine, Department of Experimental and Clinical Medical Science, University of Udine, Udine, Italy), Annoni, Giorgio, Bruni Adriana Antonella, Castagna Alberto (Clinica Geriatrica, Università degli Studi di Milano- Bicocca, Dipartimento di Scienze della Salute, AO San Gerardo, Monza), Spinelli Diana (Medicina Interna 1a, Dipartimento di Scienze Cliniche, e di Comunità, Fondazione, Irccs, Università di Milano), Corazza Gino Roberto, Miceli, Emanuela, Padula Donatella (Clinica Medica, I, Reparto, 11, IRCCS Policlinico San Matteo di Pavia, Pavia), Schinco, Giuseppina, Spreafico Sibilla (UOC Geriatria, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico), Secchi Beatrice (UOC Medicina Interna, Ospedale, Bassini, Milano), Vanoli, Massimo, Casella Gianluca (SC Medicina Interna, Azienda Ospedaliera della Provincia di Lecco, Ospedale di Merate, Lecco), Serra Maria Grazia (UOC Medicina, Panico', Azienda Ospedaliera 'Cardinale G., Lecce), Longo, Stefania, Antonaci Salvatore (UOC Medicina Interna, Azienda Ospedaliera Policlinico, Bari), Belfiore, Anna, Giuseppe Palasciano, Frualdo Mariella (Clinica Medica 'A. Murri'-Direttore Prof., Ventrella, Francesco, Iamele Luigi (Struttura Complessa di Medicina Interna, Cerignola, Asl, Foggia), Bianco Cesare (UOC Medicina Interna, Tropea), Santovito, Donato, Mezzetti, Andrea, Cipollone Francesco (Centro di Eccellenza Europeo, e di Riferimento Regionale per l'Aterosclerosi, l'Ipertensione Arteriosa, e le Dislipidemie, Università, Chieti), Nicolai, Salvatore, Salvati Filippo (UO Medicina Interna, Ospedale di Ortona, ASL 02 Abruzzo), Rini Giovan Battista, Scozzari Francesca (UOC Medicina Interna ed Ipertensione, Dipartimento Biomedico di Medicina Interna e Specialistica (Di. Bi. M. I., S), Giaccone' di Palermo), Policlinico 'P., Muiesan Maria Lorenza, Salvetti, Massimo, Bazza Abramo (Dipartimento di Scienze Cliniche, e Sperimentali, Università di Brescia, 2° Medicina Generale Spedali Civili, Brescia), Picardi, Antonio, De Vincentis Antonio (UOC Medicina Clinica, Policlinico Universitario Campus Bio-Medico, Cosio, Paolo, Terzolo Massimo (Medicina Interna, 1, Dipartimento di Scienze Cliniche, e Biologiche, AOU San Luigi Gonzaga, Università di Torino), Madaffari, Bruno, Parasporo Bruno (UO Medicina Interna, Azienda Ospedaliera Bianchi Melacrino Morelli, Reggio, Calabria), Fenoglio, Luigi, Bracco, Christian, Melchio Remo (SC Medicina Interna, Croce e Carle, AO S., Cuneo), Gentili, Tamira, Salvi Aldo (Medicina Generale, - Settore Subintensivo, Azienda, Ospedaliero-Universitaria, Ancona), Nitti, Cinzia, Falsetti Lorenzo (Medicina Generale, - Settore Ordinario, Gabrielli, Armando, Paglione Ivano (Clinica Medica, Capucci, Alessandro, Brambatti, Michela, Sparagna Armando (Clinica di Cardiologia, Ospedale, Torrette, Tirotta Daniela (UO Medicina Generale IV, Ospedale, Cervesi, Cattolica), Andreozzi, Paola, Ettorre, Evaristo, Cipriani Elisa (Area Geriatria, DAI Medicina Interna, Sapienza-Università di Roma, Rossi Fanelli Fillippo, Delfino Massimo (UOC Medicina Interna, H, Immunologia, Clinica, Nutrizione, Clinica, Endocrinologia, Glorioso, Nicola, Melis, Giada, Marras, Gianfranca, Matta Michela (Ambulatorio Ipertensione Arteriosa, e Patologie Correlate, Aou, Sassari, Sassari), Sacco Andrea (UOC Medicina Interna, PO Madonna delle Grazie, Matera), Stellitano, Elio, Scordo Anna (UO Medicina, PO 'Tiberio Evoli', Melito Porto Salvo), Russo, Franco, Caruso Assunta Antonietta (UOC Medicina Generale di Rogliano, AO di Cosenza), Porreca, Ettore, Santilli, Francesca, Tana Marco (UO Medicina Interna, e Geriatria, Ospedale Clinicizzato Colle Dell'Ara, D'Annunzio, Università G., Chieti-Pescara), Ferri, Claudio, Grassi, Davide, Di Giosia Paolo (Divisione di Medicina Interna Universitaria, - Ospedale San Salvatore, Dipartimento, Mesva, Università, Dell'Aquila, L'Aquila), Portincasa Piero (Clinica Medica 'Murri', Dipartimento di Scienze Mediche, e Oncologia Umana, Università degli Studi di Bari), Muscianisi Giuseppe (ASP Reggio Calabria, Saline Joniche), Giordani, Sara, Stanghellini Vincenzo (Dipartimento di Scienze Mediche, e Chirurgiche, Università degli Studi di Bologna), Sabbà, Carlo, Suppressa Patrizia (UOC Geriatria e Centro di assistenza, e ricerca sovraziendale per le malattie rare, Mancuso, Giuseppe, Bartone, Mosè, Calipari Daniela (UOC Medicina Interna, Presidio, Ospedaliero, ASP di Catanzaro), Arcidiacono, Giuseppe, Bellanuova Ignazio (UOC Cardiologia, e UTIC, Catania), Ferraro, Maria, Scalzo, Antonio, Marigliano Giampietro (ASP Cosenza), Cozzolino, Domenico, Lampitella, Antonio, Acri Vera (Dipartimento di Internistica Clinica, e Sperimentale, Galasso, Domenico, Mazzei, Francesca, Galasso Salvatore (RSA Madonna di Porto Gimigliano, Catanzaro), Buratti Alberto (Azienda Ospedaliera della Provincia di Pavia, UO Medicina Interna, Ospedale, Civile, Casorate, Primo, Porta, Massimo, Brizzi Maria Felice (SC Medicina Interna 1U, Azienda, Ospedaliera, Torino), Fattorini, Annalisa, Sampietro, Francesca, D’Angelo Armando (Coagulation Service and Thrombosis Research Unit, IRCCS Ospedale San Raffaele, Pala, Marco, Fabbian, Fabio, Manfredini Roberto (UOC Clinica Medica, Anna, Azienda Ospedaliera-Universitaria S., Ferrara), Moroni, Carlo, Valente, Lucia, Lopreiato Francesco (Laboratorio di Ecocardiografia-Cardiologia Preventiva, DAI Cuore, e Grossi Vasi, Parente Fernando (UOC Medicina Interna, Granata Massimo (Immunologia Clinica, A, Moia, Marco, Braham Simon (Fondazione IRCCS Ca'Granda, Ospedale Maggiore Policlinico, Rossi, Marco, Pesce Margherita (Dipartimento di Medicina Clinica, e Sperimentale, Università di Pisa), Gentile, Adelina, Catozzo Vania (UO Medicina, Ldp, Loreto, Ferranti, Edoardo, Soldini, Maurizio, Di Napoli Mariarosaria, Baciarello Giacinto (UOC Cardiologia Preventiva, e Riabilitativa, Rancan, Elena, Ageno, Walter, Guasti Luigina (Dipartimento di Medicina Clinica, e Sperimentale, Università, Dell'Insubria, Varese), Ciccaglioni, Antonio, Negri, Silvia, Polselli Marco (Centro Elettro-Stimolazione Cardiaca, Prisco Domenico (SOD Patologia Medica, Aou, Careggi, Firenze), Pignataro Francesca Serena, Pastori, Daniele, Ferro, Domenico, Loffredo, Lorenzo, Cangemi, Roberto, Perri, Ludovica, Polimeni, Licia, Catasca, Elisa, Raparelli, Valeria, Napoleone, Laura, Schillizzi, Marianna, Vicario, Tommasa, Russo, Roberta, Gentile Maria Cristina, Saliola, Mirella, Del Ben Maria, Angelico Francesco (I Clinica Medica, Sapienza-Università di, Roma)., Violi F, Daví G, Hiatt W, Lip GY, Corazza GR, Perticone F, Proietti M, Pignatelli P, Vestri AR, Basili S, ARAPACIS Study Investigators: […, Alessandri C, Serviddio G, Fascetti S, Serra P, Palange P, Greco E, Bruno G, Averna M, Giammanco A, Sposito P, De Cristofaro R, De Gennaro L, Loria P, Pellegrini E, Cominacini L, Mozzini C, Spovieri 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, Licata G, Tuttolomondo A, Conigliaro R, Pinto A, Di Raimondo D, Signorelli S, Anzaldi M, De Palma D, Galderisi M, Cudemo G, Galletti F, Fazio V, De Luca N, Meccariello A, Caputo D, De Donato MT, Iannuzi A, Bresciani A, Giunta R, Cimini C, Utili R, Durante M, Emanuele AF, Adinolfi LE, Cristiana S, Restivo L, Bellis P, Tirelli P, Sacerdoti D, Pesce P, Vanni D, Iuliano L, Palazzuoli A, Cacciafesta M, Gueli N, Capeci W, Tarquino N, Pellegrini F, Vincentelli GM, Ravallese F, Santini C, Letizia C, Petramala L, Zinnamosca L, Cilli M, Savoriti C, Falaschi P, Martocchia A, Stefanelli M, Marigliano V, Lo Iacono C, Brusco S, Bertazzoni G, El Halabieh Elias A, Paradiso M, Lizzi EM, Stefano T, Paola B, Cerci S, Ciavolella M, Di Veroli C, Malci F, De Ciocchis A, Abate D, Castellino P, Curto I, Vecchio C, Mannarino E, Pasqualini L, Fattori C, Pende A, Denegri A, Nathan A, Ricchio R, Fimognari FL, Alletto M, Messina S, Sesti G, Arturi F, Gembiale A, Scarpino PE, Carullo G, Pierluigi F, Battaglia G, Vadili G, Atzori S, Delitala G, Davì G, Angelucci E, Simona S, Giancarlo T, De Feudis L, Di Michele D, Fava A, Balsano C, De Ciantis P, Giovambattista D, Camerota A, Migliacci R, Porciello G, Mezzetti M, Gresele P, Vedovati C, Fierro T, Puccetti L, Scarpini F, Bertolotti M, Mussi C, Boddi M, Savino A, Contri S, Saller A, Fabris F, Pesavento R, Filippi L, Vedovetto V, Puato M, Treleani M, Maselli M, Corradin ML, Giantin V, Semplicini A, Minuz P, Calabria S, Romano S, Fantin F, Manica A, Stockner I, Pattis P, Guttman B, Catena C, Colussi GL, Annoni G, Bruni AA, Castagna A, Miceli E, Padula D, Schinco G, Spreafico S, Secchi B, Vanoli M, Casella G, Serra MG, Longo S, Antonaci S, Belfiore A, Frualdo M, Francesco V, Iamele L, Bianco C, Santovito D, Mezzetti A, Cipollone F, Nicolai S, Salvati F, Battista RG, Scozzari F, Muiesan ML, Salvetti M, Bazza A, Picardi A, De Vincentis A, Cosio P, Terzolo M, Fenoglio L, Bracco C, Melchio R, Gentili T, Salvi A, Nitti C, Falsetti L, Gabrielli A, Paglione I, Capucci A, Brambatti M, Sparagna A, Tirotta D, Andreozzi P, Ettorrre E, Cipriani E, Fanelli Fillippo R, Delfino M, Glorioso N, Melis G, Marras G, Matta M, Sacco A, Stellitano E, Scordo A, Russo F, Caruso Assunta A, Porreca E, Santilli F, Tana M, Ferri C, Grassi D, Di Giosia P, Portincasa P, Muscianisi G, Giordani S, Stanghellini V, Sabbà C, Supressa P, Mancuso G, Bartone M, Calipari D, Arcidiacono G, Bellanuova I, Ferraro M, Scalzo A, Marigliano G, Cozzolina D, Lampitella A, Acri V, Galasso D, Mazzei F, Galasso S, Buratti A, Porto M, Brizzi MF, Fattorini A, Sampietro F, D'Angelo A, Pala M, Fabbian F, Manfredini R, Moroni C, Valente L, Lopreiato F, Parente F, Granata M, Moia M, Braham S, Rossi M, Pesce M, Gentile A, Catozzzo V, Ferranti E, Soldini M, Di Napoli M, Baciarello G, Rancan E, Ageno W, Guasti L, Ciccaglioni A, Negri S, Polselli M, Prisco D, Pignataro FS, Pastori D, Ferro D, Loffredo L, Cangemi R, Perri L, Polimeni L, Catasca E, Raparelli V, Napoleone L, Schillizzi M, Vicario T, Russo R, Gentile MC, Saliola M, Del Ben M, Angelico F, Farcomeni A, Di Tanna G, Davi' G, Traisci G, Montebianco Abenavoli L, Grembiale A, Di Minno G, Durante ME, Pattoneri P, Boari B, Fabio G, Perego F, Bianchi Paola I, Angeli A, Colombo BM, Giannelli G, Vidili G, Torres D, Hijazl D, Gatta A, Mannucci Mannuccio P, Licata G., and …]

Subjects
Adult, Male, Risk, therapy, atrial fibrillation, cardiovascular disease, peripheral vascular disease, Aged, Atrial Fibrillation, Female, Humans, Internal Medicine, Italy, Middle Aged, Peripheral Arterial Disease, Prevalence, Registries, Societies, Medical, Ankle Brachial Index, ATRIAL FIBRILLATION, Cardiology and Cardiovascular Medicine, Medical, RISK FACTORS, cardiovascular diseases, Societies
Abstract

To the Editor: Nonvalvular atrial fibrillation (NVAF) is the most common sustained arrhythmia encountered in clinical practice and is associated with a 5-fold increased risk for stroke (1). Moreover, patients with NVAF often suffer from atherosclerotic complications such as acute myocardial infarction (AMI) (2). Peripheral artery disease (PAD) is an established marker of systemic atherosclerosis but its prevalence in NVAF is still unclear. We reasoned that inclusion of ankle-brachial index (ABI), which is an established tool for diagnosis of PAD (3), in the CHA2DS2-VASc (4) score would better define the prevalence of vascular disease. To address this issue, the Italian Society of Internal Medicine (SIMI) established an Italian registry documenting ABI in NVAF patients. The Atrial Fibrillation Registry for the ARAPACIS (Ankle-brachial Index Prevalence Assessment: Collaborative Italian Study) study is an independent research project involving all Regional Councils of SIMI. The first objective of the study was to estimate the prevalence of ABI ≤0.90 in NVAF patients. Consecutive patients with NVAF referred to internal medicine wards were eligible for the enrollment. Enrollment started in October 2010 and continued until October 30, 2012. Patients were enrolled if they were 18 years or older and had a diagnosis of NVAF, recording during the qualifying admission/consultation or in the preceding 12 months, and if it was possible to obtain the ABI measurement. Exclusion criteria included the following: acquired or congenital valvular AF, active cancer, disease with life expectancy 0.90 (93% vs. 82%; p < 0.0001). Logistic regression analysis demonstrated that ABI ≤0.90 was significantly associated with a smoking habit (odds ratio [OR]: 1.99; 95% confidence interval [CI]: 1.48 to 2.66; p < 0.0001), diabetes (OR: 1.93; 95% CI: 1.51 to 2.46; p < 0.0001), age class 65 to 74 years (OR: 2.05; 95% CI: 1.40 to 3.07; p < 0.0001), age class ≥75 years (OR: 3.12; 95% CI: 2.16 to 4.61; p < 0.0001), and history of previous transient ischemic attack/stroke (OR: 1.64; 95% CI: 1.20 to 2.24; p = 0.002). Vascular disease, as assessed by the history elements of CHA2DS2VASc score, was recorded in 17.3% of patients; inclusion of ABI ≤0.90 in the definition of vascular disease yielded a total prevalence of 33%. A higher prevalence of vascular disease was detected if ABI ≤0.90 was included in the CHA2DS2VASc score (Fig. 1). CHA2DS2VASc including ABI ≤0.90 was more associated with previous stroke (43%; OR: 1.85; 95% CI: 1.41 to 2.44; p < 0.0001) compared to CHA2DS2VASc with ABI 0.91 to 1.39 (23%; OR: 1.52; 95% CI: 1.10 to 2.11; p = 0.0117). To the best of our knowledge, there is no large-scale study that specifically examined the prevalence of ABI ≤0.90 in NVAF. In our population, 21% had ABI ≤0.90 indicating that NVAF is often associated with systemic atherosclerosis. The CHADS2 has been recently refined with the CHA2DS2-VASc score, which includes vascular disease as documented by a history of AMI, symptomatic PAD, or detection of atherosclerotic plaque in the aortic arch (4). Comparison of vascular prevalence as assessed by CHA2DS2-VASc score and/or ABI ≤0.90 is of interest to define the potentially positive impact of measuring ABI in the management of NVAF patients. Inclusion of ABI ≤0.90 in the definition of vascular disease greatly increased the prevalence of vascular disease, which increased from 17.3% (based on history alone) to 33% (based on ABI) in the entire population. If ABI ≤0.90 was encompassed in the definition of vascular disease of CHA2DS2-VASc score the prevalence of vascular disease increased in every risk class. Inclusion of ABI ≤0.90 in the CHA2DS2-VASc score allowed us to better define the risk profile of NVAF patients with an up-grading of the risk score in each CHA2DS2-VASc score category. This may have important therapeutic implications if the new score could be tested prospectively, as a higher number of NVAF patients would potentially be candidates for an anticoagulant treatment by measuring ABI. A prospective study is, therefore, necessary to validate the risk score of this new definition of vascular disease. In conclusion, this study provides the first evidence that one-fifth of NVAF patients had an ABI ≤0.90, indicating that it may represent a simple and cheap method to better define the prevalence of vascular disease in NVAF.

Published
2013

110. Analysis of foveation duration and repeatability at different gaze positions in patients affected by congenital nystagmus

Author

M. Cesarelli, P. Bifulco, M. Romano, G. Pasquariello, A. Fratini, L. Loffredo, A. Magli, DE BERARDINIS, TERESA, Cesarelli, M., Bifulco, P., Romano, M., Pasquariello, G., Fratini, A., Loffredo, L., Magli, A., and DE BERARDINIS, Teresa

Subjects
EOG, Visual acuity, Conenital nystagmu
Abstract

Congenita nustagmus is a disturbance of the oculomotor centers.Current therapies aim to icrease the patient's visual acuity by means of refraction defect correction, drug delivery and ocular muscles surgery.Eye movement recording supports for accurate diagnosis and therapy evaluation. Selected patients eye movements were recorded by using EOG or infrared oculography devices. Computation of CN concise parameters allows in depth analysis of foveations and estimation of visual acuity at different gaze. Preliminary results show a maximum of visual acuity at a specific gaze angle, this angle is mostly located at the patient right side.

Published
2007

112. Eye Movement Baseline Oscillation and Variability of Eye Position During Foveation in Congenital Nystagmus

Author

Paolo, Bifulco, Mario, Cesarelli, Luciano, Loffredo, Mario, Sansone, Marcello, Bracale, Bifulco, Paolo, Cesarelli, Mario, L., Loffredo, Sansone, Mario, Bracale, Marcello, Bifulco, P., Cesarelli, M., Loffredo, L., and Sansone, M.

Subjects
Adult, Male, Fovea Centralis, Adolescent, Eye Movements, foveation periods, Visual Acuity, eye-movement baseline, Eye, congenital nystagmu, Oscillometry, Humans, Female, Child, Nystagmus, Congenital
Abstract

Despite the inability to maintain steady fixation, congenital nystagmus does not necessarily reduce visual acuity, that can be achieved during the foveation periods. The duration of the foveation period, but also the cycle-to-cycle variability of eye position and velocity during foveations play an important role. A quantitative relationship that relates visual acuity with foveation time and cycle-to-cycle variability of eye position during foveation has been previously proposed. In many infrared-oculographic and electro-oculographic eye position recordings of our database, a sinusoidal-like oscillation of the baseline was observed, on which the nystagmus waveforms lay. This oscillation may contribute to increase cycle-to-cycle variability during foveations. The aim of this work is to extract the baseline oscillation from the recordings and to verify its relationship with eye position variability during foveation. On the basis of the observations, the baseline oscillation was assumed to be sinusoidal, and was estimated (using a least mean square technique) from eye movement signals recorded during fixation intervals, at different gaze positions, from 20 patients affected by congenital nystagmus with low visual acuity. The average baseline oscillation amplitude was 1.31 degrees, while the average frequency was 0.34 Hz. Baseline oscillation amplitude was well correlated (with a coefficient of 0.66) to the standard deviations of eye-position during foveation, which in turn is connected to visual acuity.

Published
2003

114. Sensorial and motor evaluation of dyslexia: preliminary report

Author

L. Loffredo, M. Cesarelli, G. D’Addio, R. De Marco, R. M. Bove, M. Acquaviva, F. D’Esposito, AMBROSIO, GENNARO, Loffredo, L., Cesarelli, M., Ambrosio, Gennaro, D’Addio, G., De Marco, R., Bove, R. M., Acquaviva, M., and D’Esposito, F.

Published
1994

116. Visual function before and after photorefractive keratectomy for myopia

Author

Nicola Rosa, Rocco De Marco, G. Ambrosio, Luciano Loffredo, Giovanni Cennamo, Adolfo Sebastiani, Ambrosio, G, Cennamo, Giovanni, De Marco, R, Loffredo, L, Rosa, N, and Sebastiani, A.

Subjects
Adult, medicine.medical_specialty, Adolescent, Light, genetic structures, medicine.medical_treatment, media_common.quotation_subject, Group ii, Vision Disorders, Visual Acuity, Contrast Sensitivity, Cornea, Ophthalmology, Glare testing, Refractive surgery, Myopia, medicine, Humans, Scattering, Radiation, Contrast (vision), Prospective Studies, Vision, Ocular, Dioptre, media_common, business.industry, Glare (vision), Middle Aged, eye diseases, Photorefractive keratectomy, Visual function, Surgery, Laser Therapy, sense organs, business
Abstract

BACKGROUND: To date, Snellen visual acuity and postoperative refraction have been used to evaluate the results of photorefractive keratectomy. However, other parameters, such as contrast sensitivity function and glare, may be affected by refractive surgery and lead to unsatisfactory visual performance. This prospective study is aimed at evaluating the effect of photorefractive keratectomy on contrast sensitivity function and glare. SUBJECTS AND METHODS: Static contrast sensitivity function, dynamic contrast sensitivity function, and glare sensitivity were evaluated in 22 myopic eyes before as well as 1, 3, and 6 months after photorefractive keratectomy. The eyes tested were divided into three groups, according to the amount of myopia: group I, from - 4.00 to - 8.00 diopters (D); group II, from -8.25 to -11.00 D; group ??, from -11.25 to -20.00 D. RESULTS: Both static and dynamic contrast sensitivity function at the intermediate spatial frequencies were altered at 1 month after photorefractive keratectomy, with a trend toward recovery at 3 and 6 months postoperatively. Glare sensitivity was not significantly affected by surgery. CONCLUSIONS: Contrast sensitivity function and glare testing may show abnormalities in the presence of optimal visual and refractive results. These tests may result especially important for the evaluation of new refractive surgical procedures. [J Refract Corneal Surg. 1994;10:129-136.]

Published
1994

117. Rate and predictors of thromboprophylaxis in internal medicine wards: Results from the AURELIO study.

Author

Magna A, Maggio E, Vidili G, Sciacqua A, Cogliati C, Di Giulio R, Bernardini S, Fallarino A, Palumbo IM, Pannunzio A, Bagnato C, Serra C, Boddi M, Falsetti L, Zaccone V, Ettorre E, Desideri G, Santoro L, Cantisani V, Pignatelli P, Santoliquido A, Violi F, and Loffredo L

Subjects
Humans, Female, Male, Aged, Prospective Studies, Middle Aged, Aged, 80 and over, Hospitalization, Risk Factors, Venous Thrombosis prevention & control, Risk Assessment, Anticoagulants therapeutic use, Internal Medicine, Venous Thromboembolism prevention & control
Abstract

Background: Randomized controlled trials suggest that prophylactic doses of anticoagulants effectively prevent venous thromboembolism (VTE) in hospitalized medical patients with high thromboembolic risk. However, no prospective studies exist regarding the real-world prevalence of prophylactic anticoagulant use. This prospective study aimed to determine the rate and predictors of thromboprophylaxis in an unselected population of patients hospitalized in medical departments., Methods: We conducted a multicenter prospective observational study (AURELIO - rAte of venous thrombosis in acutely iLl patIents hOspitalized) to assess the rate of deep vein thrombosis (DVT) in unselected acutely ill patients hospitalized in medical wards using compression ultrasound (CUS) at admission and discharge. Additionally, we evaluated the rate of pharmacological thromboprophylaxis administration in this population and analyzed the thrombotic risk by assessing RAMs (Risk Assessment Models) such as the IMPROVE-VTE and PADUA scores following the clinician's decision to administer thromboprophylaxis. Patients with IMPROVE-VTE scores ≥3 and/or PADUA scores ≥4 were classified as high thrombotic risk; those with IMPROVE-VTE scores <3 and/or PADUA scores <4 were classified as low risk., Results: We recruited 2371 patients (1233 males [52 %] and 1138 females [48 %]; mean age 72 ± 16 years). The median length of hospitalization was 13 ± 12 days. Overall, 442/2371 (18.6 %) patients received prophylactic parenteral anticoagulants (subcutaneous low weight molecular heparin or fondaparinux once daily) at admission. Assessing the thrombotic risk of the population recruited 1016 (42.9 %) patients were classified as high risk and 1354 (57.1 %) were low risk. Among high-risk patients, 339/1016 (33.4 %) received anticoagulant prophylaxis compared to 103/1354 (7.6 %) low-risk patients. During hospitalization, 9 patients developed DVT, comprising 7 asymptomatic and 2 symptomatic cases of proximal DVT. Of these, 3 patients were on anticoagulant prophylaxis, while 6 were not. Among the high-risk population, 7 out of 1016 patients (0.7 %) experienced proximal DVT during hospitalization, with 2 out of these 7 (28 %) receiving anticoagulant thromboprophylaxis. In the low-risk population, 2 out of 1354 patients (0.2 %) developed DVT, with 1 out of these 2 (50 %) receiving anticoagulant thromboprophylaxis. Age, heart or respiratory failure, pneumonia, active neoplasia, previous VTE, reduced mobility, and absence of kidney failure were more frequent in patients receiving prophylaxis. Multivariable logistic regression identified age (RR 1.010; CI 95 % 1002-1019; p = 0.015), heart/respiratory failure (RR 1.609; CI 95 % 1248-2075; p < 0.0001), active neoplasia (RR 2.041; CI 95 % 1222-2141; p < 0.0001), pneumonia (RR 1.618; CI 95 % 1557-2676; p < 0.0001), previous VTE (RR 1.954; CI 95 % 1222-3125; p < 0.0001), and reduced mobility (RR 4.674; CI 95 % 3700-5905; p < 0.0001) as independent predictors of thromboprophylaxis., Conclusions: This study, conducted without pre-established thromboembolic risk scores, offers a comprehensive view of venous thromboembolism prophylaxis in medical patients with acute conditions hospitalized in internal medicine departments. It reveals that advanced age, heart or respiratory failure, active cancer, pneumonia, previous VTE, and reduced mobility are predictors that may influence the decision to administer thromboprophylaxis in these patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2024
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118. Impaired arterial dilation and increased NOX2 generated oxidative stress in subjects with ataxia-telangiectasia mutated (ATM) kinase.

Author

Loffredo L, Soresina A, Cinicola BL, Capponi M, Salvatori F, Bartimoccia S, Picchio V, Forte M, Caputi C, Poscia R, Leuzzi V, Spalice A, Pignatelli P, Badolato R, Duse M, Violi F, Carnevale R, and Zicari AM

Subjects
Humans, Female, Male, Adolescent, Child, Cross-Sectional Studies, Mutation, Young Adult, Nitric Oxide metabolism, Vasodilation genetics, Ataxia Telangiectasia Mutated Proteins genetics, Ataxia Telangiectasia Mutated Proteins metabolism, Oxidative Stress, NADPH Oxidase 2 genetics, NADPH Oxidase 2 metabolism, Ataxia Telangiectasia genetics, Ataxia Telangiectasia metabolism
Abstract

Background: Subjects with mutations in the Ataxia-Telangiectasia mutated (ATM) gene encoding for ATM kinase have a greater predisposition to develop atherosclerosis, but the mechanism behind this phenomenon is not yet understood. NADPH oxidase type 2 may play a role in this process, leading to endothelial dysfunction and an increased susceptibility to thrombosis. The purpose of this study was to assess the redox state in individuals with ATM mutations and determine its impact on endothelial function., Methods: In this cross-sectional study, twenty-seven children with ataxia telangiectasia (AT) (13 males and 14 females, mean age 15.1 ± 7.6 years) were compared with 27 controls (13 males and 14 females, mean age 14.6 ± 8.4 years) matched for age and gender. Additionally, 29 AT parents with heterozygous mutation of ATM (h-ATM) gene, and 29 age- and gender-matched controls were included. Endothelial function was evaluated through brachial flow-mediated dilation (FMD) and the assessment of nitric oxide (NO) bioavailability. Oxidative stress was evaluated by measuring serum activity of soluble NOX2-dp (sNOX2-dp), hydrogen peroxide (H 2 O 2 ) production, and hydrogen breakdown activity (HBA). Thrombus formation was assessed through the Total Thrombus Formation Analysis System (T-TAS)., Results: AT children and parents with heterozygous ATM mutations exhibited significantly lower FMD, HBA, and NO bioavailability as compared to age and gender matched controls. AT children and ATM carrier of heterozygous ATM mutations had significantly higher concentrations of sNOX2-dp and H 2 O 2 as compared to controls. Compared to the respective controls, AT children and their parents, who carried heterozygous ATM mutation, showed an accelerated thrombus growth as revealed by reduced occlusion time. Multivariable linear regression analysis revealed that sNOX2 (standardized coefficient β: -0.296; SE: 0.044; p = 0.002) and NO bioavailability (standardized coefficient β: 0.224; SE: 0.065; p = 0.02) emerged as the only independent predictive variables associated with FMD (R 2 : 0.44)., Conclusions: This study demonstrates that individuals with ATM mutations experience endothelial dysfunction, increased oxidative stress, and elevated thrombus formation. These factors collectively contribute to the heightened susceptibility of these individuals to develop atherosclerosis., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Published
2024
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120. Vitamin E supplementation (alone or with other antioxidants) and stroke: a meta-analysis.

Author

Maggio E, Bocchini VP, Carnevale R, Pignatelli P, Violi F, and Loffredo L

Subjects
Humans, Randomized Controlled Trials as Topic, Incidence, Vitamin E administration & dosage, Antioxidants administration & dosage, Dietary Supplements, Stroke prevention & control, Stroke epidemiology
Abstract

Context: A previous study showed that vitamin E is effective in reducing the incidence of myocardial infarction only when it is taken in the absence of other antioxidants. It is unclear if it also reduces the incidence of stroke., Objective: The aim of this meta-analysis is to compare the effect of vitamin E supplementation alone or combined with other antioxidants on the incidence of stroke., Data Sources: A search was performed in the following databases: PubMed, ISI Web of Science, SCOPUS, and Cochrane Library., Data Extraction: Sixteen randomized controlled trials were selected to evaluate the effect of vitamin E supplementation on stroke., Data Analysis: The range of vitamin E doses used was 33-800 IU. The follow-up period ranged from 6 months to 9.4 years. Compared with controls, when vitamin E was given alone it did not reduce the incidence of ischemic and hemorrhagic stroke. Conversely, compared with controls, supplementation of vitamin E with other antioxidants reduced ischemic stroke (random effects, RR: 0.91; 95% CI: 0.84-0.99; P = 0.02) but with a significant increase in hemorrhagic stroke (random effects, RR: 1.22; 95% CI: 1.0-1.48; P = 0.04)., Conclusions: Supplementation with vitamin E alone is not associated with stroke reduction. Instead, supplementation of vitamin E with other antioxidants reduces the incidence of ischemic stroke but increases the risk of hemorrhagic stroke, cancelling any beneficial effect derived. Thus, vitamin E is not recommended in stroke prevention., Systematic Review Registration: PROSPERO registration no. CRD42022258259., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Published
2024
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122. In adult X-CGD patients, regulatory T cells are expanded while activated T cells display a NOX2-independent ROS increase.

Author

Cammarata I, Pinna V, Pacella I, Rotella I, Soresina A, Badolato R, Plebani A, Pignata C, Cirillo E, Zicari AM, Violi F, Carnevale R, Loffredo L, and Piconese S

Subjects
Adult, Humans, T-Lymphocytes, Regulatory, NADPH Oxidases genetics, NADPH Oxidases metabolism, Reactive Oxygen Species metabolism, Mutation, Granulomatous Disease, Chronic genetics, Granulomatous Disease, Chronic metabolism
Abstract

The X-linked chronic granulomatous disease (X-CGD), a rare genetic disease characterised by recurrent infections, is caused by mutations of NOX2. Significant proportions of X-CGD patients display signs of immune dysregulation. Regulatory T cells (Tregs) are CD4 + T lymphocytes that expand in active inflammation and prevent autoimmune disorders. Here we asked whether X-CGD is associated to Treg dysfunctions in adult patients. To this aim, the frequency of Tregs was analysed through intracellular flow cytometry in a cohort of adult X-CGD patients, carriers and controls. We found that Tregs were significantly expanded and activated in blood of adult X-CGD patients, and this was associated with activation of conventional CD4 + T cells (Tconvs). T cell activation was characterised by accumulation of intracellular ROS, not derived from NOX2 but likely produced by cellular metabolism. The higher TNF production by Tconvs in X-CGD patients might contribute to the expansion of Tregs through the TNFR2 receptor. In summary, our data indicate that Tregs expand in adult X-CGD in response to immune activation, and that the increase of NOX2-independent ROS content is a feature of activated T cells., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Published
2024
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123. Effect of traditional or heat-not-burn cigarette smoking on circulating miRNAs in healthy subjects.

Author

Picchio V, Ferrero G, Cozzolino C, Pardini B, Floris E, Tarallo S, Dhori X, Nocella C, Loffredo L, Biondi-Zoccai G, Carnevale R, Frati G, Chimenti I, and Pagano F

Subjects
Humans, Hot Temperature, Healthy Volunteers, Circulating MicroRNA, Cigarette Smoking, MicroRNAs genetics, Neoplasms
Abstract

Background: Traditional combustion cigarette (TCC) smoking is an established risk factor for several types of cancer and cardiovascular diseases. Circulating microRNAs (miRNAs) represent key molecules mediating pathogenetic mechanisms, and potential biomarkers for personalized risk assessment. TCC smoking globally changes the profile of circulating miRNAs. The use of heat-not-burn cigarettes (HNBCs) as alternative smoking devices is rising exponentially worldwide, and the circulating miRNA profile of chronic HNBC smokers is unknown. We aimed at defining the circulating miRNA profile of chronic exclusive HNBC smokers, and identifying potentially pathogenetic signatures., Methods: Serum samples were obtained from 60 healthy young subjects, stratified in chronic HNBC smokers, TCC smokers and nonsmokers (20 subjects each). Three pooled samples per group were used for small RNA sequencing, and the fourth subgroup constituted the validation set., Results: Differential expression analysis revealed 108 differentially expressed miRNAs; 72 exclusively in TCC, 10 exclusively in HNBC and 26 in both smoker groups. KEGG pathway analysis on target genes of the commonly modulated miRNAs returned cancer and cardiovascular disease associated pathways. Stringent abundance and fold-change criteria nailed down our functional bioinformatic analyses to a network where miR-25-3p and miR-221-3p are main hubs., Conclusion: Our results define for the first time the miRNA profile in the serum of exclusive chronic HNBC smokers and suggest a significant impact of HNBCs on circulating miRNAs., (© 2023 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Published
2024
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124. Impact of heat-not-burn cigarette passive smoking on children's oxidative stress, endothelial and platelet function.

Author

Loffredo L, Carnevale R, Pannunzio A, Cinicola BL, Palumbo IM, Bartimoccia S, Nocella C, Cammisotto V, Violi F, Biondi-Zoccai G, Frati G, and Zicari AM

Subjects
Child, Humans, Hydrogen Peroxide, Hot Temperature, Oxidative Stress physiology, Isoprostanes, Tobacco Smoke Pollution adverse effects, Tobacco Products, Thrombosis
Abstract

Growing global use of heat-not-burn cigarettes (HNBC) prompts investigation. Prior studies assessed HNBC's effects on cardiovascular health, revealing heightened oxidative stress, platelet activation, and endothelial dysfunction. However, limited understanding exists regarding passive smoking's impact on children exposed to HNBC. This study aims to assess levels of oxidative stress, endothelial and platelet function among children exposed to passive smoke from HNBC, traditional tobacco (TT) cigarettes and unexposed subjects. Seventy-eight children (2-18 years) were divided into three groups: HNBC passive smokers (n = 26), TT cigarette exposed (n = 26), and control (CNT) group (n = 26, unexposed). Oxidative stress was evaluated by serum NADPH oxidase-2 (NOX2) activity, assessed by soluble Nox2-derived peptide (sNOX2-dp), isoprostanes, hydrogen peroxide (H 2 O 2 ) production, hydrogen break-down activity (HBA) and NO bioavailability. Endothelial function was assessed by brachial flow-mediated dilation (FMD). Platelet function was evaluated by soluble CD40 ligand (sCD40L), soluble P-selectin (sP-selectin) and thrombus formation by T-TAS analysis. Passive smoking-exposed children (both HNBC and TT) exhibited significantly increased serum sNOX2-dp, isoprostanes, H2O2, sCD40L sP-selectin and thrombus formation versus controls. Conversely, exposed children displayed reduced brachial FMD and serum NO bioavailability. No significant differences were found between children exposed to passive smoking of HNBC vs TT. Multivariable regression linked sNOX2 (standardized coefficient β: 0.284; SE: 0.040; p = 0.01) and H 2 O 2 (standardized coefficient β: 0.243; SE: 0.0; p = 0.02) as independent predictors of FMD, and isoprostanes (standardized coefficient β:0.388; SE: 0.022; p < 0.001) and serum cotinine (standardized coefficient β:0.270; SE: 0.048; p = 0.01) with sNOX2-dp levels. Exposure to HNBC smoke heightened oxidative stress, endothelial dysfunction, platelet activation, and thrombus formation in children. Findings suggest avenues for interventions to curb childhood passive smoking exposure., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lorenzo Loffredo reports financial support was provided by University of Rome La Sapienza. Lorenzo Loffredo reports a relationship with University of Rome La Sapienza that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Published
2024
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125. Immunological characterization of an Italian PANDAS cohort.

Author

Leonardi L, Lorenzetti G, Carsetti R, Piano Mortari E, Guido CA, Zicari AM, Förster-Waldl E, Loffredo L, Duse M, and Spalice A

Abstract

This cross-sectional study aimed to contribute to the definition of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) pathophysiology. An extensive immunological assessment has been conducted to investigate both immune defects, potentially leading to recurrent Group A β-hemolytic Streptococcus (GABHS) infections, and immune dysregulation responsible for a systemic inflammatory state. Twenty-six PANDAS patients with relapsing-remitting course of disease and 11 controls with recurrent pharyngotonsillitis were enrolled. Each subject underwent a detailed phenotypic and immunological assessment including cytokine profile. A possible correlation of immunological parameters with clinical-anamnestic data was analyzed. No inborn errors of immunity were detected in either group, using first level immunological assessments. However, a trend toward higher TNF-alpha and IL-17 levels, and lower C3 levels, was detected in the PANDAS patients compared to the control group. Maternal autoimmune diseases were described in 53.3% of PANDAS patients and neuropsychiatric symptoms other than OCD and tics were detected in 76.9% patients. ASO titer did not differ significantly between the two groups. A possible correlation between enduring inflammation (elevated serum TNF-α and IL-17) and the persistence of neuropsychiatric symptoms in PANDAS patients beyond infectious episodes needs to be addressed. Further studies with larger cohorts would be pivotal to better define the role of TNF-α and IL-17 in PANDAS pathophysiology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Leonardi, Lorenzetti, Carsetti, Piano Mortari, Guido, Zicari, Förster-Waldl, Loffredo, Duse and Spalice.)

Published
2024
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126. Reply to Özdemir, Ö. Allergic Disease with Selective IgA Deficiency. Comment on "Cinicola et al. The Allergic Phenotype of Children and Adolescents with Selective IgA Deficiency: A Longitudinal Monocentric Study. J. Clin. Med. 2022, 11 , 5705".

Author

Cinicola BL, Brindisi G, Capponi M, Gori A, Loffredo L, De Castro G, Anania C, Spalice A, Guido CA, Milito C, Duse M, Quinti I, Pulvirenti F, and Zicari AM

Abstract

We carefully read the correspondence [...].

Published
2023
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127. Endothelial dysfunction, oxidative stress and low-grade endotoxemia in COVID-19 patients hospitalised in medical wards.

Author

Ciacci P, Paraninfi A, Orlando F, Rella S, Maggio E, Oliva A, Cangemi R, Carnevale R, Bartimoccia S, Cammisotto V, D'Amico A, Magna A, Nocella C, Mastroianni CM, Pignatelli P, Violi F, and Loffredo L

Subjects
Humans, Lipopolysaccharides, Hydrogen Peroxide, Interleukin-6, Tumor Necrosis Factor-alpha, Oxidative Stress, Endotoxemia diagnosis, COVID-19 diagnosis, Vascular Diseases, Pneumonia
Abstract

Background: Endothelial dysfunction, assessed by flow-mediated dilation (FMD), is related to poor prognosis in patients with COVID-19 pneumonia (CP). In this study, we explored the interplay among FMD, NADPH oxidase type 2 (NOX-2) and lipopolysaccharides (LPS) in hospitalised patients with CP, community acquired pneumonia (CAP) and controls (CT)., Methods: We enrolled 20 consecutive patients with CP, 20 hospitalised patients with CAP and 20 CT matched for sex, age, and main cardiovascular risk factors. In all subjects we performed FMD and collected blood samples to analyse markers of oxidative stress (soluble Nox2-derived peptide (sNOX2-dp), hydrogen peroxide breakdown activity (HBA), nitric oxide (NO), hydrogen peroxide (H2O2)), inflammation (TNF-α and IL-6), LPS and zonulin levels., Results: Compared with controls, CP had significant higher values of LPS, sNOX-2-dp, H2O2,TNF-α, IL-6 and zonulin; conversely FMD, HBA and NO bioavailability were significantly lower in CP. Compared to CAP patients, CP had significantly higher levels of sNOX2-dp, H2O2, TNF-α, IL-6, LPS, zonulin and lower HBA. Simple linear regression analysis showed that FMD inversely correlated with sNOX2-dp, H2O2, TNF-α, IL-6, LPS and zonulin; conversely FMD was directly correlated with NO bioavailability and HBA. Multiple linear regression analysis highlighted LPS as the only predictor of FMD., Conclusion: This study shows that patients with COVID-19 have low-grade endotoxemia that could activate NOX-2, generating increased oxidative stress and endothelial dysfunction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Published
2023
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128. Case Report: Interindividual variability and possible role of heterozygous variants in a family with deficiency of adenosine deaminase 2: are all heterozygous born equals?

Author

Pulvirenti F, Cinicola BL, Ferrari S, Guadagnolo D, Sculco E, Capponi M, Loffredo L, Sciannamea M, Insalaco A, Quinti I, De Benedetti F, and Zicari AM

Subjects
Male, Female, Adolescent, Humans, Child, Adult, Adenosine Deaminase genetics, Intercellular Signaling Peptides and Proteins, Agammaglobulinemia diagnosis, Agammaglobulinemia genetics, Agammaglobulinemia complications, Vasculitis etiology
Abstract

Deficiency of adenosine deaminase 2 (DADA2) is a rare systemic autoinflammatory disease, typically with autosomal recessive inheritance, usually caused by biallelic loss of function mutations in the ADA2 gene. The phenotypic spectrum is broad, generally including fever, early-onset vasculitis, stroke, and hematologic dysfunction. Heterozygous carriers may show related signs and symptoms, usually milder and at an older age. Here we describe the case of two relatives, the proband and his mother, bearing an ADA2 homozygous pathogenic variant, and a heterozygous son. The proband was a 17-year-old boy with intermittent fever, lymphadenopathies, and mild hypogammaglobulinemia. He also had sporadic episodes of aphthosis, livedo reticularis and abdominal pain. Hypogammaglobulinemia was documented when he was 10 years old, and symptoms appeared in his late adolescence. The mother demonstrated mild hypogammaglobulinemia, chronic pericarditis since she was 30 years old and two transient episodes of diplopia without lacunar lesions on MRI. ADA2 (NM&#95;001282225.2) sequencing identified both mother and son as homozygous for the c.1358A>G, p.(Tyr453Cys) variant. ADA2 activity in the proband and the mother was 80-fold lower than in the controls. Clinical features in both patients improved on anti-tumor necrosis factor therapy. An older son was found to be heterozygous for the same mutation post-mortem. He died at the age of 12 years due to a clinical picture of fever, lymphadenitis, skin rash and hypogammaglobulinemia evolving toward fatal multiorgan failure. Biopsies of skin, lymph nodes, and bone marrow excluded lymphomas and vasculitis. Despite being suspected of symptomatic carrier, the contribution of an additional variant in compound heterozygosity, or further genetic could not be ruled out, due to poor quality of DNA samples available. In conclusion, this familiar case demonstrated the wide range of phenotypic variability in DADA2. The search for ADA2 mutations and the assessment of ADA2 activity should be considered also in patients with the association of hypogammaglobulinemia and inflammatory conditions, also with late presentation and in absence of vasculitis. Furthermore, the clinical picture of the deceased carrier suggests a possible contribution of heterozygous pathogenic variants to inflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pulvirenti, Cinicola, Ferrari, Guadagnolo, Sculco, Capponi, Loffredo, Sciannamea, Insalaco, Quinti, De Benedetti and Zicari.)

Published
2023
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129. Low Grade Endotoxemia and Oxidative Stress in Offspring of Patients with Early Myocardial Infarction.

Author

Cinicola BL, Palumbo IM, Pannunzio A, Carnevale R, Bartimoccia S, Cammisotto V, Capponi M, Brindisi G, Salvatori F, Barillà F, Martino F, D'Amico A, Poscia R, Spalice A, Zicari AM, Violi F, and Loffredo L

Abstract

Background and aims : Offspring of patients with early myocardial infarction are at higher cardiovascular risk, but the underlying physio-pathological mechanism is unclear. NADPH oxidase-type 2 (NOX-2) plays a pivotal role as mediator of oxidative stress and could be involved in activating platelets in these patients. Furthermore, altered intestinal permeability and serum lipopolysaccharide (LPS) could be a trigger to promote NOX-2 activation and platelet aggregation. This study aims to evaluate the behavior of low grade endotoxemia, oxidative stress and platelet activation in offspring of patients with early myocardial infarction. Methods: We enrolled, in a cross-sectional study, 46 offspring of patients with early myocardial infarction and 86 healthy subjects (HS). LPS levels and gut permeability (assessed by zonulin), oxidative stress (assessed by serum NOX-2-derived peptide (sNOX2-dp) release, hydrogen peroxide (H 2 O 2 ) production and isoprostanes), serum nitric oxide (NO) bioavailability and platelet activation (by serum thromboxane B2 (TXB2) and soluble P-Selectin (sP-Selectin)) were analyzed. Results: Compared to HS, offspring of patients with early myocardial infarction had higher values of LPS, zonulin, serum isoprostanes, sNOX2-dp H 2 O 2 , TXB2, p-selectin and lower NO bioavailability. Logistic regression analysis showed that the variables associated with offspring of patients with early myocardial infarction were LPS, TXB2 and isoprostanes. The multiple linear regression analysis confirmed that serum NOX-2, isoprostanes, p-selectin and H 2 O 2 levels were significantly associated to LPS. Furthermore, serum LPS, isoprostanes and TXB2 levels were significantly associated with sNOX-2-dp. Conclusions: Offspring of patients with early myocardial infarction have a low grade endotoxemia that could generate oxidative stress and platelet activation increasing their cardiovascular risk. Future studies are needed to understand the role of dysbiosis in this population.

Published
2023
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130. Association between PaO 2 /FiO 2 ratio and thrombotic events in COVID-19 patients.

Author

Loffredo L, Pignatelli P, Pirro M, Ceccarelli G, Oliva A, Maggio E, Cancelli F, D'Ardes D, Amitrano M, Zicari AM, Cinicola BL, Taliani G, Cangemi R, Lichtner M, Falcone M, Orlando F, Pugliese F, Venditti M, Mastroianni CM, and Violi F

Subjects
Humans, Hypoxia, Hospitalization, Retrospective Studies, COVID-19 complications, Thrombosis epidemiology, Thrombosis etiology, Thrombophilia
Abstract

PaO 2 /FiO 2 (P/F ratio) is considered a marker of hypoxia/hypoxemia and mortality. Several prothrombotic changes are associated with the decrease of P/F ratio. The role of P/F ratio in patients with arterial and venous thrombosis remains unclear. The aim of this study was to assess in patients with coronavirus disease 2019 (COVID-19), the association between P/F ratio and arterial/venous thrombosis. One thousand and four hundred and six COVID-19 patients were recruited; 289 (21%) patients had P/F ratio < 200 and 1117 (79%) ≥ 200. Compared to the patients with P/F ratio ≥ 200, those with P/F ratio < 200 were older and with higher levels of glycemia, D-dimer and lower levels of albumin. Multiple linear regression analysis showed that albumin (standardized coefficient β:  0.156; SE: 0.001; p = 0.0001) and D-dimer (standardized coefficient β: -0.135; SE: 0.0001; p = 0.0001) were associated with P/F ratio. During the hospitalization 159 patients were transferred in intensive care unit (ICU), 253 patients died, 156 patients had arterial or venous thrombotic events. A bivariate logistic analysis was performed to analyze the predictors of thrombosis in COVID-19 patients; P/F ratio < 200 (Odds Ratio: [OR] 1.718, 95% Confidence Interval [CI] 1.085-2.718, p = 0.021), albumin (OR 1.693, 95% CI 1.055-2.716, p = 0.029), D-dimer (OR 3.469, 95% CI 2.110-5.703, p < 0.0001), coronary artery disease (CAD) (OR 1.800, 95% CI 1.086-2.984, p = 0.023) and heart failure (OR 2.410 95% CI 1.385-4.193, p = 0.002) independently predicted thrombotic events in this population. This study suggests that the P/F ratio is associated with thrombotic events by promoting a hypercoagulation state in patients hospitalized for COVID-19., (© 2023. The Author(s).)

Published
2023
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131. Structure, Activation, and Regulation of NOX2: At the Crossroad between the Innate Immunity and Oxidative Stress-Mediated Pathologies.

Author

Nocella C, D'Amico A, Cammisotto V, Bartimoccia S, Castellani V, Loffredo L, Marini L, Ferrara G, Testa M, Motta G, Benazzi B, Zara F, Frati G, Sciarretta S, Pignatelli P, Violi F, Carnevale R, and Group S

Abstract

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) is a multisubunit enzyme complex that participates in the generation of superoxide or hydrogen peroxide (H 2 O 2 ) and plays a key role in several biological functions. Among seven known NOX isoforms, NOX2 was the first identified in phagocytes but is also expressed in several other cell types including endothelial cells, platelets, microglia, neurons, and muscle cells. NOX2 has been assigned multiple roles in regulating many aspects of innate and adaptive immunity, and human and mouse models of NOX2 genetic deletion highlighted this key role. On the other side, NOX2 hyperactivation is involved in the pathogenesis of several diseases with different etiologies but all are characterized by an increase in oxidative stress and inflammatory process. From this point of view, the modulation of NOX2 represents an important therapeutic strategy aimed at reducing the damage associated with its hyperactivation. Although pharmacological strategies to selectively modulate NOX2 are implemented thanks to new biotechnologies, this field of research remains to be explored. Therefore, in this review, we analyzed the role of NOX2 at the crossroads between immunity and pathologies mediated by its hyperactivation. We described (1) the mechanisms of activation and regulation, (2) human, mouse, and cellular models studied to understand the role of NOX2 as an enzyme of innate immunity, (3) some of the pathologies associated with its hyperactivation, and (4) the inhibitory strategies, with reference to the most recent discoveries.

Published
2023
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132. Toll-Like Receptor 4-Dependent Platelet-Related Thrombosis in SARS-CoV-2 Infection.

Author

Carnevale R, Cammisotto V, Bartimoccia S, Nocella C, Castellani V, Bufano M, Loffredo L, Sciarretta S, Frati G, Coluccia A, Silvestri R, Ceccarelli G, Oliva A, Venditti M, Pugliese F, Maria Mastroianni C, Turriziani O, Leopizzi M, D'Amati G, Pignatelli P, and Violi F

Subjects
Humans, Antibodies, Monoclonal pharmacology, Blood Platelets metabolism, Cross-Sectional Studies, SARS-CoV-2, Thromboxanes metabolism, Thromboxanes pharmacology, Toll-Like Receptor 4 metabolism, COVID-19 metabolism, Thrombosis etiology, Thrombosis metabolism
Abstract

Background: SARS-CoV-2 is associated with an increased risk of venous and arterial thrombosis, but the underlying mechanism is still unclear., Methods: We performed a cross-sectional analysis of platelet function in 25 SARS-CoV-2 and 10 healthy subjects by measuring Nox2 (NADPH oxidase 2)-derived oxidative stress and thromboxane B 2 , and investigated if administration of monoclonal antibodies against the S protein (Spike protein) of SARS-CoV-2 affects platelet activation. Furthermore, we investigated in vitro if the S protein of SARS-CoV-2 or plasma from SARS-CoV-2 enhanced platelet activation., Results: Ex vivo studies showed enhanced platelet Nox2-derived oxidative stress and thromboxane B 2 biosynthesis and under laminar flow platelet-dependent thrombus growth in SARS-CoV-2 compared with controls; both effects were lowered by Nox2 and TLR4 (Toll-like receptor 4) inhibitors. Two hours after administration of monoclonal antibodies, a significant inhibition of platelet activation was observed in patients with SARS-CoV-2 compared with untreated ones. In vitro study showed that S protein per se did not elicit platelet activation but amplified the platelet response to subthreshold concentrations of agonists and functionally interacted with platelet TLR4. A docking simulation analysis suggested that TLR4 binds to S protein via three receptor-binding domains; furthermore, immunoprecipitation and immunofluorescence showed S protein-TLR4 colocalization in platelets from SARS-CoV-2. Plasma from patients with SARS-CoV-2 enhanced platelet activation and Nox2-related oxidative stress, an effect blunted by TNF (tumor necrosis factor) α inhibitor; this effect was recapitulated by an in vitro study documenting that TNFα alone promoted platelet activation and amplified the platelet response to S protein via p47phox (phagocyte oxidase) upregulation., Conclusions: The study identifies 2 TLR4-dependent and independent pathways promoting platelet-dependent thrombus growth and suggests inhibition of TLR4. or p47phox as a tool to counteract thrombosis in SARS-CoV-2.

Published
2023
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133. External validation of the ADA score for predicting thrombosis among acutely ill hospitalized medical patients from the APEX Trial.

Author

Chi G, Violi F, Pignatelli P, Vestri A, Spagnoli A, Loffredo L, Hernandez AF, Hull RD, Cohen AT, Harrington RA, Goldhaber SZ, and Gibson CM

Subjects
Humans, Enoxaparin therapeutic use, Risk Assessment, Anticoagulants therapeutic use, Risk Factors, COVID-19 complications, Venous Thrombosis diagnosis, Venous Thrombosis drug therapy, Venous Thrombosis chemically induced, Venous Thromboembolism diagnosis, Venous Thromboembolism drug therapy, Venous Thromboembolism chemically induced
Abstract

The ADA (Age-D-dimer-Albumin) score was developed to identify hospitalized patients at an increased risk for thrombosis in the coronavirus infectious disease-19 (COVID-19) setting. The study aimed to validate the ADA score for predicting thrombosis in a non-COVID-19 medically ill population from the APEX trial. The APEX trial was a multinational, randomized trial that evaluated the efficacy and safety of betrixaban vs. enoxaparin among acutely ill hospitalized patients at risk for venous thromboembolism. The study endpoints included the composite of arterial or venous thrombosis and its components. Metrics of model calibration and discrimination were computed for assessing the performance of the ADA score as compared to the IMPROVE score, a well-validated VTE risk assessment model. Among 7,119 medical inpatients, 209 (2.9%) had a thrombosis event up to 77 days of follow-up. The ADA score demonstrated good calibration for both arterial and venous thrombosis, whereas the IMPROVE score had adequate calibration for venous thrombosis (p > 0.05 from the Hosmer-Lemeshow test). For discriminating arterial and venous thrombosis, there was no significant difference between the ADA vs. IMPROVE score (c statistic = 0.620 [95% CI: 0.582 to 0.657] vs. 0.590 [95% CI: 0.556 to 0.624]; ∆ c statistic = 0.030 [95% CI: -0.022 to 0.081]; p = 0.255). Similarly, for discriminating arterial thrombosis, there was no significant difference between the ADA vs. IMPROVE score (c statistic = 0.582 [95% CI: 0.534 to 0.629] vs. 0.609 [95% CI: 0.564 to 0.653]; ∆ c statistic = -0.027 [95% CI: -0.091 to 0.036]; p = 0.397). For discriminating venous thrombosis, the ADA score was modestly superior to the IMPROVE score (c statistic = 0.664 [95% CI: 0.607 to 0.722] vs. 0.573 [95% CI: 0.521 to 0.624]; ∆ c statistic = 0.091 [95% CI: 0.011 to 0.172]; p = 0.026). The ADA score had a higher sensitivity (0.579 [95% CI: 0.512 to 0.646]; vs. 0.440 [95% CI: 0.373 to 0.507]) but lower specificity (0.625 [95% CI: 0.614 to 0.637] vs. 0.747 [95% CI: 0.737 to 0.758]) than the IMPROVE score for predicting thrombosis. Among acutely ill hospitalized medical patients enrolled in the APEX trial, the ADA score demonstrated good calibration but suboptimal discrimination for predicting thrombosis. The findings support the use of either the ADA or IMPROVE score for thrombosis risk assessment. The applicability of the ADA score to non-COVID-19 populations warrants further research.Clinical Trial Registration: http://www.clinicaltrials.gov . Unique identifier: NCT01583218., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Published
2023
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134. Effect of COVID-19 lockdown on refractive errors in Italian children aged 5-12 years: A multi-center retrospective study.

Author

Trovato Battagliola E, Mangiantini P, D'Andrea M, Malvasi M, Loffredo L, Scalinci SZ, Comberiati AM, Migliorini R, and Pacella E

Subjects
Humans, Child, Retrospective Studies, Communicable Disease Control, Refraction, Ocular, COVID-19 epidemiology, Refractive Errors, Myopia, Hyperopia
Abstract

Purpose: to explore the potential consequences of the COVID-19 lockdown on the prevalence of myopia among Italian children aged 5-12 years., Materials and Methods: retrospective multicenter study conducted in Italy. Population: children aged 5-12. Selection: random selection of children who received an eye exam between 2016 to 2021. Inclusion criteria: healthy children presenting for a routine eye exam. Exclusion criteria: presence of ocular comorbidities other than refractive error, such as blepharoptosis, media opacities, corneal or retinal dystrophies, strabismus, amblyopia, or concurrent therapy with atropine 0.01%. Outcome measure: age and spherical equivalent (SE) measured in diopters (D) in the right eye (RE) in cycloplegia. Statistical analysis: ANOVA test., Results: total of 803 children. In the years prior to COVID-19, the mean SE ± SD of healthy age-school children was: 0.54 ± 1.49 D in 2016; 0.43 ± 1.84 D in 2017; 0.34 ± 1.41 D in 2018; 0.35 ± 1.75 D in 2019 (ANOVA, p = .659). In 2021, the mean SE changed to -0.08 ± 1.44 D (ANOVA, p = .005). Mean age was comparable in all groups (ANOVA, p = .307). The prevalence of myopes (SE ≤-0.5D) and hyperopes (SE ≥ 2D) was respectively 24.10% and 9.64% among children aged 60-96 months, and 63.86% and 6.02% among children aged 97-144 months. These values represent a statistically-significant increase in the number of myopes (Chi-square, p = .016) and decrease in the number of hyperopes (Chi-square, p = .001), as compared to previous years (.06 and.48 respectively)., Conclusion: this retrospective study shows a statistically-significant decrease in the mean SE in children aged 5-12 in the year following the COVID-19 lockdown. The percentage of myopes has increased significantly, while the percentage of hyperopes has decreased. The lifestyle changes caused by the lockdown led children to spend more time on near-work activities and digital devices, and less time outdoors. These are known risk factors for the development and progression of myopia. Studies in different countries are encouraged.

Published
2023
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137. Asymptomatic and symptomatic deep venous thrombosis in hospitalized acutely ill medical patients: risk factors and therapeutic implications.

Author

Loffredo L, Vidili G, Sciacqua A, Cogliati C, Di Giulio R, Bernardini S, Ciacci P, Pietrangelo A, Orlando F, Paraninfi A, Boddi M, Di Minno G, Falsetti L, Lodigiani C, Santoliquido A, Ettorre E, Pignatelli P, Arezzo MF, Gutu E, Harenberg J, and Violi F

Abstract

Background: Acutely ill medical patients experience deep venous thrombosis (DVT) during the hospitalization, however the time course of DVT is still unclear., Objectives: To evaluate risk factors in acutely ill hospitalized medical patients for proximal asymptomatic DVT (ADVT) and symptomatic DVT (SDVT) at admission and discharge., Patients/methods: In this prospective observational study, consecutive acutely ill medical patients (hospitalized mainly for acute medical disease as infections, neoplasm, anemia, heart failure) underwent compression ultrasonography (CUS) of proximal lower limb veins within 48 h from admission and at discharge to diagnose ADVT and SDVT. Covid-19 patients, anticoagulant therapy, surgical procedures, acute SDVT, and acute pulmonary embolism, were exclusion criteria. Biographical characteristics at hospitalization, D-Dimer (assessed by ELISA)) and DD-improve score., Results: Of 2,100 patients (1002 females, 998 males, age 71 ± 16 years) 58 (2.7%) had proximal ADVT at admission. Logistic regression analysis showed that age, and active cancer were independently associated with ADVT at admission. The median length of hospitalization was 10 days [interquartile range: 6-15]. During the hospital stay, 6 patients (0.3%) with a negative CUS at admission experienced DVT (2 SDVT and 4 ADVT). In the subgroup of patients (n = 1118), in whom D-dimer was measured at admission, D-Dimer and IMPROVE-DD score were associated with ADVT at admission (n = 37) and with all DVT (n = 42) at discharge. ROC curve defined an IMPROVE-DD score of 2.5 as the optimal cut-off for discriminating patients with and without thrombotic events., Conclusions: We provide evidence of early development of ADVT in unselected acutely ill medical patients suggesting the need of investigating patients by CUS immediately after hospital admission (within 48 h). Advanced age, active cancer, known thrombophilia and increased IMPROVE-DD score may identify patients at risk. The benefit of anticoagulation needs to be investigated in patients with these specific risk factors and negative CUS at admission., Trial Registration: NCT03157843., (© 2022. The Author(s).)

Published
2022
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138. The Allergic Phenotype of Children and Adolescents with Selective IgA Deficiency: A Longitudinal Monocentric Study.

Author

Cinicola BL, Brindisi G, Capponi M, Gori A, Loffredo L, De Castro G, Anania C, Spalice A, Guido CA, Milito C, Duse M, Quinti I, Pulvirenti F, and Zicari AM

Abstract

Background: Selective IgA deficiency (SIgAD) is the most common inborn error of immunity. The exact prevalence and pathogenesis of allergy in SIgAD have not yet been defined. We aimed to describe the prevalence and the characteristics of allergy in pediatric SIgAD subjects, evaluate the association between allergy and other comorbidities, and define the immune phenotype of allergic and non-allergic patients., Methods: Clinical and immunological data from 67 SIgAD patients were collected over a 13-year period at a single center. Patients' characteristics were analyzed according to the presence of allergy., Results: Allergy was diagnosed in 34% of SIgAD patients, with a median age at allergy diagnosis of 8 years. Allergy was the second-most-common clinical manifestation, following recurrent respiratory infections. Among the allergic group, 74% had rhinitis, 30% asthma, 30% atopic dermatitis, and 22% food allergy; one out of three had more than one allergic manifestation. SIgAD patients showed more frequent transitory lymphopenia and a lower count of CD19+ at diagnosis than at last FU. However, compared to non-allergic subjects, allergic patients did not differ in their immune phenotype, number and severity of infections, or increased autoimmunity., Conclusions: In our longitudinal study, compared to non-allergic SIgAD patients, those with allergies did not present a more severe immune defect or complex clinical phenotype. However, evaluation and early identification of allergy in the context of SIgAD assessment, both at diagnosis and during FU, and definition of a proper management are important to prevent complications and improve the patient's quality of life.

Published
2022
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139. Natural Activators of Autophagy Increase Maximal Walking Distance and Reduce Oxidative Stress in Patients with Peripheral Artery Disease: A Pilot Study.

Author

Martinelli O, Peruzzi M, Bartimoccia S, D'Amico A, Marchitti S, Rubattu S, Chiariello GA, D'Ambrosio L, Schiavon S, Miraldi F, Saade W, D'Abramo M, Pingitore A, Loffredo L, Nocella C, Forte M, and Pignatelli P

Abstract

Trehalose, spermidine, nicotinamide, and polyphenols have been shown to display pro-autophagic and antioxidant properties, eventually reducing cardiovascular and ischemic complications. This study aimed to investigate whether a mixture of these components improves maximal walking distance (MWD) in peripheral artery disease (PAD) patients. Nitrite/nitrate (NOx), endothelin-1, sNOX2-dp, H2O2 production, H2O2 break-down activity (HBA), ATG5 and P62 levels, flow-mediated dilation (FMD), and MWD were evaluated in 20 PAD patients randomly allocated to 10.5 g of mixture or no-treatment in a single-blind study. The above variables were assessed at baseline and 60 days after mixture ingestion. Compared with baseline, mixture intake significantly increased MWD (+91%; p < 0.01) and serum NOx (+96%; p < 0.001), whereas it significantly reduced endothelin-1 levels (−30%, p < 0.01). Moreover, mixture intake led to a remarkable reduction in sNOX2dp (−31%, p < 0.05) and H2O2 (−40%, p < 0.001) and potentiated antioxidant power (+110%, p < 0.001). Finally, mixture ingestion restored autophagy by increasing ATG5 (+43%, p < 0.01) and decreasing P62 (−29%, p < 0.05). No changes in the above-mentioned variables were observed in the no-treatment group. The treatment with a mixture of trehalose, spermidine, nicotinamide, and polyphenols improves MWD in PAD patients, with a mechanism possibly related to NOX2-mediated oxidative stress downregulation and autophagic flux upregulation. Clinical Trial Registration unique identifier: NCT04061070.

Published
2022
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141. The ADA (Age-D-Dimer-Albumin) Score to Predict Thrombosis in SARS-CoV-2.

Author

Violi F, Pignatelli P, Vestri AR, Spagnoli A, Cipollone F, Ceccarelli G, Oliva A, Amitrano M, Pirro M, Taliani G, Cangemi R, Lichtner M, Pugliese F, Falcone M, D'Ardes D, Venditti M, Mastroianni CM, and Loffredo L

Subjects
Fibrin Fibrinogen Degradation Products, Humans, SARS-CoV-2, Serum Albumin, COVID-19, Thrombosis
Abstract

Background:  Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-related pneumonia is associated with venous and arterial thrombosis. Aim of the study was to find out a new score for predicting thrombosis in patients with SARS-CoV-2., Methods:  We included a cohort of 674 patients affected by SARS-CoV-2, not requiring intensive care units, and followed-up during the hospitalization until discharge. Routine analyses performed at in-hospital admission included also serum albumin and D-dimer while arterial and venous thromboses were the endpoints of the study., Results:  During the follow-up, 110 thrombotic events were registered; patients with thrombotic events were older and had lower albumin and higher D-dimer, compared with thrombotic event-free ones. On multivariable logistic regression with step-by-step procedure age, serum albumin, and D-dimer were independently associated with thrombotic events. The linear combination of age, D-dimer, and albumin allowed to build-up the ADA (age-D-dimer-albumin) score, whose area under the curve (AUC) was 0.752 (95% confidence interval [CI], 0.708-0.795). ADA score was internally validated by bootstrap sampling procedure giving an AUC of 0.752 (95% CI: 0.708-0.794)., Conclusion:  Combination of age, D-dimer, and albumin in the ADA score allows identifying SARS-CoV-2 patients at higher risk of thrombotic events., Competing Interests: None declared., (Thieme. All rights reserved.)

Published
2022
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142. (R)Evolution in Allergic Rhinitis Add-On Therapy: From Probiotics to Postbiotics and Parabiotics.

Author

Capponi M, Gori A, De Castro G, Ciprandi G, Anania C, Brindisi G, Tosca M, Cinicola BL, Salvatori A, Loffredo L, Spalice A, and Zicari AM

Abstract

Starting from the "Hygiene Hypothesis" to the "Microflora hypothesis" we provided an overview of the symbiotic and dynamic equilibrium between microbiota and the immune system, focusing on the role of dysbiosis in atopic march, particularly on allergic rhinitis. The advent of deep sequencing technologies and metabolomics allowed us to better characterize the microbiota diversity between individuals and body sites. Each body site, with its own specific environmental niches, shapes the microbiota conditioning colonization and its metabolic functionalities. The analysis of the metabolic pathways provides a mechanistic explanation of the remote mode of communication with systems, organs, and microflora of other body sites, including the ecosystem of the upper respiratory tract. This axis may have a role in the development of respiratory allergic disease. Notably, the microbiota is significant in the development and maintenance of barrier function; influences hematopoiesis and innate immunity; and shows its critical roles in Th1, Th2, and Treg production, which are necessary to maintain immunological balance and promote tolerance, taking part in every single step of the inflammatory cascade. These are microbial biotherapy foundations, starting from probiotics up to postbiotics and parabiotics, in a still-ongoing process. When considering the various determinants that can shape microbiota, there are several factors to consider: genetic factors, environment, mode of delivery, exposure to antibiotics, and other allergy-unrelated diseases. These factors hinder the engraftment of probiotic strains but may be upgradable with postbiotic and parabiotic administration directly on molecular targets. Supplementation with postbiotics and parabiotics could represent a very exciting perspective of treatment, bypassing probiotic limitations. At present, this avenue remains theoretical and to be explored, but it will certainly be a fascinating path to follow.

Published
2022
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144. Sex-Related Differences in Oxidative, Platelet, and Vascular Function in Chronic Users of Heat-not-Burn vs. Traditional Combustion Cigarettes.

Author

Schirone L, Loffredo L, Carnevale R, Battaglia S, Marti R, Pizzolo S, Bartimoccia S, Nocella C, Cammisotto V, Saade W, Tanzilli A, Sciarretta S, Chimenti I, De Falco E, Cavarretta E, Picchio V, Peruzzi M, Marullo A, Miraldi F, Violi F, Morelli A, Biondi-Zoccai G, and Frati G

Abstract

Smoking is still a major cardiovascular risk factor, despite many public awareness campaigns and dedicated interventions. Recently, modified risk products (MRP), e.g., heat-not-burn cigarettes (HNBCs), have been introduced as surrogates of traditional combustion cigarettes (TCCs). Although these products are promoted as healthier than TCCs, few studies have been conducted to assess it. This work is a sex-focused sub-study of a prospective observational study in which apparently healthy chronic TCC smokers were age-matched with regular HNBC users. Blood samples were collected for biochemical assays and blood pressure and flow-mediated dilation (FMD) were measured. Out of 60 subjects, 33 (55%) were women, and 27 (45%) men, with 11 (33%) vs. 9 (33%) non-smokers, respectively, 10 (30%) vs. 10 (37%) TCC smokers, and 12 (36%) vs. 8 (30%) HNBC smokers (p = 0.946). Bivariate and multivariable analyses showed no statistically significant between-sex differences in NO, H2O2, sCD40L, sNox2-dp, sP-selectin, platelet aggregation, cotinine or FMD, overall, in non-smokers, in TCC smokers, or in HNBC smokers (all p > 0.05). HNBCs appeared safer than TCCs when focusing on Nox2-dp (p = 0.026) and sP-selectin (p = 0.050) but had similar levels of the other measured markers. In conclusion, HNBCs have similar detrimental effects on women and men’s oxidative stress (H2O2: p = 0.49; sNox2-dp: p = 0.31) and platelet activation (sP-selectin: p = 0.33; platelet aggregation p = 0.87).

Published
2022
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145. Building a foundation in self-awareness: Genetic counseling students' experiences with self-care, reflection, and mindfulness.

Author

Bulmer L, Stanley C, Loffredo L, Mills R, and Doyle L

Subjects
Anxiety psychology, Genetic Counseling, Humans, Self Care, Students, Mindfulness methods
Abstract

Stress and anxiety are significant concerns for practicing genetic counselors as well as genetic counseling students and can have downstream effects on patient care. Prior research suggests graduate-level training in self-awareness practices such as self-care, reflection, and mindfulness could have lasting effects for genetic counselors, their patients, and the profession as a whole. This mixed-methods study assessed self-awareness among 154 genetic counseling graduate students using the Self-Reflection and Insight Scale (SRIS), the Mindfulness Attention Awareness Scale (MAAS), and self-described experiences with self-awareness practice. Genetic counseling students had significantly lower mean scores on the MAAS and the Insight subscale of the SRIS compared with other health professionals, indicating that genetic counseling students have lower levels of mindfulness and may lack insight into their thoughts and feelings. After starting genetic counseling graduate programs, students were more likely to reduce participation in active self-awareness practices such as physical activity and mental health counseling. Most students reported having structured practice in self-care (n = 97, 63%), reflection (n = 125, 81.2%), and mindfulness (n = 77, 50%) as a part of their training programs. Second-year genetic counseling students reporting mindfulness practices had significantly higher scores on the Insight subscale of the SRIS than those who did not, indicating that students engaged in mindfulness practice are better able to understand their thoughts, feelings, and behavior. The majority of students reported benefitting from structured practice in self-care (n = 63, 64.9%), reflection (n = 101, 80%), and mindfulness (n = 54, 70.1%). Open-ended responses regarding students' perceived benefits and limitations of structured practice were analyzed for recurrent themes. Students reported improved self-awareness which enhanced their counseling relationships during clinical rotations. However, they also perceived that implementation of self-awareness practices may have been inconsistent. Findings from this study have implications for integrating self-awareness practices into genetic counseling graduate curriculum., (© 2021 National Society of Genetic Counselors.)

Published
2022
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146. Extra Virgin Olive Oil Reduces Gut Permeability and Metabolic Endotoxemia in Diabetic Patients.

Author

Bartimoccia S, Cammisotto V, Nocella C, Del Ben M, D'Amico A, Castellani V, Baratta F, Pignatelli P, Loffredo L, Violi F, and Carnevale R

Subjects
Blood Glucose metabolism, Glucagon-Like Peptide 1, Humans, Insulin, Lipopolysaccharides, Olive Oil, Permeability, Diabetes Mellitus, Endotoxemia, Prediabetic State
Abstract

Background: Extra virgin olive oil (EVOO) improves post-prandial glycemia, but the underlying mechanism has not been fully elucidated. We tested the hypothesis that EVOO improves post-prandial glycemia by reducing gut permeability-derived low-grade endotoxemia., Methods: Serum levels of lipopolysaccharides (LPS), zonulin, a marker of gut permeability, glucose, insulin and glucagon-like peptide 1 (GLP1) were measured in 20 patients with impaired fasting glucose (IFG) and 20 healthy subjects (HS) matched for sex and age. The same variables were measured in IFG patients ( n = 20) and HS ( n = 20) before and after a Mediterranean diet with 10 g EVOO added or not ( n = 20) or in IFG patients ( n = 20) before and after intake of 40 g chocolate with EVOO added or not., Results: Compared to HS, IFG had higher levels of LPS and zonulin. In HS, meal intake was associated with a significant increase of blood glucose, insulin, and GLP1 with no changes of blood LPS and zonulin. Two hours after a meal intake containing EVOO, IFG patients showed a less significant increase of blood glucose, a more marked increase of blood insulin and GLP1 and a significant reduction of LPS and zonulin compared to IFG patients not given EVOO. Correlation analysis showed that LPS directly correlated with blood glucose and zonulin and inversely with blood insulin. Similar findings were detected in IFG patients given a chocolate added or without EVOO., Conclusion: Addition of EVOO to a Mediterranean diet or chocolate improves gut permeability and low-grade endotoxemia.

Published
2022
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147. Platelet Activation Favours NOX2-Mediated Muscle Damage in Elite Athletes: The Role of Cocoa-Derived Polyphenols.

Author

D'Amico A, Cavarretta E, Fossati C, Borrione P, Pigozzi F, Frati G, Sciarretta S, Costa V, De Grandis F, Nigro A, Peruzzi M, Miraldi F, Saade W, Calogero A, Rosa P, Galardo G, Loffredo L, Pignatelli P, Nocella C, and Carnevale R

Subjects
Antioxidants metabolism, Antioxidants pharmacology, Athletes, Biomarkers, Humans, Hydrogen Peroxide metabolism, Muscle, Skeletal metabolism, Oxidative Stress, Platelet Activation, Cacao, Polyphenols metabolism, Polyphenols pharmacology
Abstract

Mechanisms of exercise-induced muscle injury with etiopathogenesis and its consequences have been described; however, the impact of different intensities of exercise on the mechanisms of muscular injury development is not well understood. The aim of this study was to exploit the relationship between platelet activation, oxidative stress and muscular injuries induced by physical exercise in elite football players compared to amateur athletes. Oxidant/antioxidant status, platelet activation and markers of muscle damage were evaluated in 23 elite football players and 23 amateur athletes. Compared to amateurs, elite football players showed lower antioxidant capacity and higher oxidative stress paralleled by increased platelet activation and muscle damage markers. Simple linear regression analysis showed that sNOX2-dp and H 2 O 2 , sCD40L and PDGF-bb were associated with a significant increase in muscle damage biomarkers. In vitro studies also showed that plasma obtained from elite athletes increased oxidative stress and muscle damage in human skeletal muscle myoblasts cell line compared to amateurs' plasma, an effect blunted by the NOX2 inhibitor or by the cell treatment with cocoa-derived polyphenols. These results indicate that platelet activation increased muscular injuries induced by oxidative stress. Moreover, NOX2 inhibition and polyphenol extracts treatment positively modulates redox status and reduce exercise-induced muscular injury.

Published
2022
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149. Allergic rhinitis, microbiota and passive smoke in children: A pilot study.

Author

Brindisi G, Marazzato M, Brunetti F, De Castro G, Loffredo L, Carnevale R, Cinicola B, Palamara AT, Conte MP, and Zicari AM

Subjects
Adolescent, Child, Dysbiosis, Humans, Pilot Projects, Smoking, Microbiota, Rhinitis, Allergic
Abstract

Background: Allergic rhinitis (AR) is one of the most common allergic diseases affecting children. Objective assessment of nasal obstruction is possible through active anterior rhinomanometry (AAR). Several factors, such as passive smoke exposure (PSE), are triggers for worsening nasal obstruction and chronic inflammation. PSE affects bacterial eubiosis in the upper respiratory tract. This study evaluates the influence of PSE and cotinine levels on both nasal obstruction and local microbiome composition in children with AR., Methods: Fifty patients (aged between 6 and 16 years) with AR monosensitized grass pollen were enrolled. They underwent skin prick tests, a nasal swab to evaluate the microbial composition of the anterior nostrils, a basal AAR, a post-decongestion AAR, and spirometry. Serum cotinine levels were assessed to evaluate PSE., Results: A significantly lower percentage of mean nasal flow (mNF%) was observed before and after hydrazine administration in subjects exposed to passive smoke (Exp group) compared with the non-exposed group. In contrast, higher cotinine levels were observed in the Exp group than in the controls. PSE has been associated with a decrease in biodiversity and a change in the nasal microbiome composition; instead, although to a different extent, the abundance of specific taxa resulted in being correlated to cotinine levels and nasal flow., Conclusion: Children with AR exposed to passive smoke with positive serum cotinine could represent a risk factor for developing nasal obstruction and microbial dysbiosis, suggesting their possible role in pathophysiological processes., (© 2022 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Published
2022
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150. Interventional study with vitamin E in cardiovascular disease and meta-analysis.

Author

Violi F, Nocella C, Loffredo L, Carnevale R, and Pignatelli P

Subjects
Antioxidants therapeutic use, Humans, Tocopherols, Vitamin E, Cardiovascular Diseases drug therapy, Cardiovascular Diseases prevention & control, Tocotrienols
Abstract

Cardiovascular disease (CVD) is one of the major causes of morbidity and mortality and atherosclerosis is the common root to most of the CVD. Oxidative stress is one of the most important factors driving atherosclerosis and its complications. Thus, strategies for the prevention and treatment of cardiovascular events had oxidative changes as a potential target. Natural vitamin E consists of a family of eight different compounds, four tocopherols and four tocotrienols. All tocopherols and tocotrienols are potent antioxidants with lipoperoxyl radical-scavenging activities. In addition, α-tocopherol possesses also anti-inflammatory as well as anti-atherothrombotic effects by modulating platelet and clotting system. Experimental and in vitro studies described molecular and cellular signalling pathways regulated by vitamin E antithrombotic and antioxidant properties. While observational studies demonstrated an inverse association between vitamin E serum levels and CVD, interventional trials with vitamin supplements provided negative results. This review focus on the impact of vitamin E in the atherothrombotic process and describes the results of experimental and clinical studies with the caveats related to the interventional trials with vitamin E to prevent CVD., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Published
2022
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