38 results on '"Tenti, E."'
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2. P346 MINIMALLY INVASIVE APPROACH FOR THE SURGICAL TREATMENT OF COMBINED MITRAL AND AORTIC VALVE DISEASE
- Author
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Fiorentino, M, primary, Mikus, E, additional, Tripodi, A, additional, Sangiorgi, D, additional, Calvi, S, additional, Tenti, E, additional, Panzavolta, M, additional, Tizzano, F, additional, and Savini, C, additional
- Published
- 2023
- Full Text
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3. P45 MINITHORACOTOMY APPROACH FOR MITRAL VALVE REDO SURGERY
- Author
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Fiorentino, M, primary, Mikus, E, additional, Tripodi, A, additional, Zucchetta, F, additional, Calvi, S, additional, Sangiorgi, D, additional, Tenti, E, additional, and Savini, C, additional
- Published
- 2023
- Full Text
- View/download PDF
4. Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial
- Author
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Perrone, F, Piccirillo, M, Ascierto, P, Salvarani, C, Parrella, R, Marata, A, Popoli, P, Ferraris, L, Marrocco-trischitta, M, Ripamonti, D, Binda, F, Bonfanti, P, Squillace, N, Castelli, F, Muiesan, M, Lichtner, M, Calzetti, C, Salerno, N, Atripaldi, L, Cascella, M, Costantini, M, Dolci, G, Facciolongo, N, Fraganza, F, Massari, M, Montesarchio, V, Mussini, C, Negri, E, Botti, G, Cardone, C, Gargiulo, P, Gravina, A, Schettino, C, Arenare, L, Chiodini, P, Gallo, C, Vitale, M, Trojaniello, C, Palla, M, Bianchi, A, De Feo, G, Miscio, L, Froldi, M, Menicanti, L, Cuppone, M, Gobbo, G, Baldessari, C, Valenti, V, Castelvecchio, S, Poli, F, Giacomazzi, F, Piccinni, R, Annnunziata, M, Biondi, A, Bussolari, C, Mazzoleni, M, Giachi, A, Filtz, A, Manini, A, Poletti, E, Masserini, F, Conforti, F, Gaudiano, G, Favero, V, Moroni, A, Viva, T, Fancoli, F, Ferrari, D, Niro, D, Resta, M, Ballotta, A, Poli, M, Ranucci, M, Tebaldi, A, Gritti, G, Pasulo, L, Gaglio, L, Del Fabbro, R, Alborghetti, L, Giustinetti, G, Columpsi, P, Cazzaniga, M, Capici, S, Sala, L, Di Sciacca, R, Mosca, G, Pirozzi, M, Franceschini, F, Roccaro, A, Salvetti, M, Paini, A, Corda, L, Ricci, C, Tomasoni, L, Nasta, P, Lorenzotti, S, Odolini, S, Foca, E, Roldan, E, Metra, M, Magrini, S, Borghetti, P, Latronico, N, Piva, S, Filippini, M, Tomasoni, G, Zuccala, F, Cattaneo, S, Scolari, F, Bossini, N, Gaggiotti, M, Properzi, M, Del Giudice, E, Marocco, R, Carraro, A, Del Borgo, C, Belvisi, V, Tieghi, T, De Masi, M, Zuccala, P, Fabietti, P, Vetica, A, Mercurio, V, Fondaco, L, Kertusha, B, Curtolo, A, Lubrano, R, Zotti, M, Puorto, A, Ciuffreda, M, Sarni, A, Monteforte, G, Romeo, D, Viola, E, Damiani, C, Barone, A, Mantovani, B, Di Sanzo, D, Gentili, V, Carletti, M, Aiuti, M, Gallo, A, Meliante, P, Martellucci, S, Riggio, O, Cardinale, V, Ridola, L, Bragazzi, M, Gioia, S, Valenzi, E, Graziosi, C, Bina, N, Fasolo, M, Ricci, S, Gioacchini, M, Lucci, A, Corso, L, Tornese, D, Nijhawan, P, Equitani, F, Cosentino, C, Palladino, M, Leonetti, F, Leto, G, Gnessi, C, Campagna, G, Cesareo, R, Marrocco, F, Straface, G, Mecozzi, A, Cerbo, L, Isgro, V, Parrocchia, S, Visconti, G, Casati, G, Ariani, A, Donghi, L, Tacconelli, E, Bertoldi, M, Cattaneo, P, Lambertenghi, L, Motta, L, Omega, L, Albano, G, Scarano, F, De Rosa, A, Buglione, A, Lavoretano, S, Gaglione, G, De Marco, M, Sangiovanni, V, Fusco, F, Viglietti, R, Manzillo, E, Rescigno, C, Pisapia, R, Plamieri, G, Maraolo, A, Calabria, G, Catalano, M, Fiorentino, G, Annunziata, A, Polistina, G, Imitazione, P, Mollica, M, Esposito, V, D'Abraccio, M, Punzi, R, Bianco, V, Sbreglia, C, Del Vecchio, R, Bordonali, A, Franco, A, Salsi, P, Fontana, M, Virzi, G, Ornella, C, Molteni, A, Gennarini, S, Gnudi, U, Ricci, M, Titolo, G, Mensi, G, Vuotto, P, Gasperini, B, Mancini, M, Pasquini, Z, Spanu, P, Clementi, S, Pierini, S, Bokor, D, Gori, D, Ciofetti, M, Caimi, M, Bettazzi, L, Allevi, E, Furiani, S, Capitanio, C, Mastropasqua, B, Fara, C, Pulitano, G, Matsuno, J, Porta, F, Dolfini, V, Beyene, N, Bezzi, M, Novali, M, Viale, P, Tedeschi, S, Pascale, R, Bruno, R, Di Filippo, A, Sachs, M, Oggionni, T, Di Stefano, M, Mengoli, C, Facchini, C, Daniele, D, Frausini, G, Mucci, L, Tedesco, S, Girolimetti, R, Manfredini, E, Di Carlo, A, Espinosa, E, Dennetta, D, Ticinesi, A, Meschi, T, Nouvenne, A, Claudio, N, Vitale, F, Saracco, M, Codeluppi, M, Fronti, E, Ferrante, P, Nespola, G, Francisci, D, Tosti, A, Carbonelli, C, Greco, A, Tinti, M, Stellini, R, Appiani, C, Reghenzi, P, Poletti, V, Ravaglia, C, Tacconi, D, Malcontenti, C, Sainaghi, P, Landi, R, Vassia, V, Rizzi, E, Bellan, M, Rossati, A, Castello, L, Mastroianni, C, Russo, G, Fabio, T, Serino, F, Brollo, L, Momesso, E, Turati, M, Monforte, A, Marchetti, G, Boni, F, Teopompi, E, Trenti, C, Boracchia, L, Minelli, E, Ghidoni, G, Matei, A, Caruso, A, Arcoleo, G, Camarda, G, Catalano, F, Spatafora, M, Bettega, D, Andreoni, M, Teti, E, Sarmati, L, Di Lorenzo, A, Celeste, M, Baratto, F, Monticelli, J, Criveller, P, Andrea, A, Anselmo, R, Castellano, M, Cappelli, C, Corvini, F, Zanini, B, Crippa, M, Ronconi, M, Costa, R, Casella, S, Brentana, L, Bernardi, L, Frascati, A, Panese, S, Presotto, F, Michieletto, L, Bernardi, C, Fusar, M, Agnoletti, V, Farina, M, Russo, Lavorini, F, Ginanni, R, Palmieri, F, Mosti, S, Amaglio, A, Cattaneo, A, Cirri, S, Montisci, A, Gallazzi, C, Cosseta, D, Baronio, B, Rampa, L, Maggi, P, Messina, V, Berlendis, M, Sabatti, M, Palumbo, M, Mazzone, A, Faggioli, P, Bussini, L, Fornaro, G, Volpato, F, Imperiale, D, Manno, E, Ferreri, E, Martelli, D, Verhovez, A, Giorgis, S, Faccio, L, Quadri, R, Negro, C, Converso, M, Bosco, F, Amadasi, S, Prandini, P, Cocchi, S, Manfrin, V, Del Punta, V, Mazzola, G, Sportato, G, Romagnoli, M, Cristini, F, Facondini, F, Perin, T, Boschi, A, Meschiari, M, Guaraldi, G, Modica, S, Moneta, S, Boccalatte, D, Marchetti, V, Ebbreo, G, Dale, M, Tura, P, Rizzoni, D, Boari, G, Bonetti, S, Marini, E, Daniele, I, Grossi, P, Delfrate, N, Bernhart, O, Spizzo, G, Mahlknecht, K, Volkl, T, Di Pietro, M, Trezzi, M, Monacci, C, Peris, A, Bonizzoli, M, Cavanna, L, Moroni, C, Stroppa, E, Savio, M, Gatti, F, Bartolaminelli, C, Petrosillo, N, Donno, D, Taglietti, F, Topino, S, Chinello, P, Galati, V, D'Offizi, G, Taibi, C, Cimolato, B, Moroni, F, Palagano, N, Pelagatti, L, Cristiana, S, Landini, G, Amitrano, M, Raimondo, M, Mangiacapra, S, Romano, A, Atteno, M, Blanc, P, Suardi, L, Pallotto, C, Casinelli, K, Uccella, I, Harari, S, Caminati, A, Lipani, F, Di Perri, G, Calcagno, A, Calleri, G, Montrucchio, C, Caputo, A, Cozzio, S, Donne, L, Bassetti, M, Malgorzata, M, Nicolini, L, Russo, C, Sepulcri, C, Beltramini, S, Mina, F, Puoti, M, Gandino, A, Langer, T, D'Amico, F, Rocchetti, C, Cettolo, F, Gabriele, F, Bocchi, P, Cioni, G, Cappi, C, Corcione, S, De Rosa, F, Scabini, S, Canta, F, Pinna, S, Pensa, A, Rocco, M, Cirasa, M, Spinicci, M, Mencarini, J, Zammarchi, L, Giovanni, C, Sciole, K, Bassi, F, Bianchi, M, Frigerio, S, Spaziani, S, Nucera, A, Rizzardini, G, Cossu, M, Antivalle, M, Carpinteri, G, Macheda, S, Labate, D, Bottiroli, M, Erne, E, Cristina, Z, Di Biase, V, Malberti, F, Montani, G, Poisa, P, Bettini, D, Cauda, R, Ciccullo, A, Riccardi, N, Angheben, A, Turrini, M, Clerici, R, Gardellini, A, Liparulo, L, Rossini, T, Ucciferri, C, Cipollone, F, Vecchiet, J, Nico, A, Marra, L, Leone, A, Sdanganelli, A, Palmiotti, G, D'Alagni, G, Santantonio, T, Caputo, S, Bottalico, I, Ponticiello, A, Di Perna, F, Bernardi, E, Beltrame, A, Bravi, S, David, M, Bernardi, P, Galante, D, Uccelli, M, Prestini, K, Drera, M, Zini, E, Peregrinelli, A, Blanzuoli, L, Benedetti, V, Calvi, R, Scaglione, N, Nallino, G, Bonazzi, M, Crespi, T, Masolin, T, Regazzetti, A, Cerri, M, Maffezzini, E, Piazza, M, Papetti, C, Filippi, C, Roveda, E, Cipolla, G, Scozzafava, M, Crepaldi, M, Henchi, S, Vanoni, N, Repossi, A, Vezzoli, M, Scorletti, E, Perugini, O, Pasini, S, Pacetti, V, Ferrari, L, de Paduanis, G, Del Duca, S, Dell'Ara, F, Brocchieri, A, Minoja, G, Storti, E, Pitagora, L, Costa, I, Delfanti, F, Orlandi, M, Ruggeri, R, Ruggieri, L, Livigni, S, Silengo, D, Ageno, W, Pedrini, L, Artiol, S, Morbidoni, L, De Donno, G, Ravagnani, V, Inglese, F, Scotton, P, Costantini, P, Delucchi, M, Clini, E, Ansuini, A, Marco, B, Giuseppe, L, Vincenzo, B, Rastelli, G, Doria, A, Vianello, A, Cattelan, A, Bindoli, S, Felicietti, M, Canetta, C, Scartabellati, A, Accordino, S, Ferrara, M, Cocco, L, Cirillo, F, Pace, E, De Caro, M, Alberico, M, Benigni, G, Damiano, T, Fusco, P, Iuorio, A, Torretta, G, Racagni, M, Muttini, S, Sala, G, Ghiringhelli, P, Chiumiento, F, Baccari, L, Luca, B, Bocchi, F, Benatti, F, Catellani, J, Coppola, M, Papi, A, Bosco, E, Lazzeri, C, Cesira, N, Puttini, C, Carli, T, Croci, L, Corridi, M, Arlotti, M, Guerrini, G, Cola, L, Romanelli, M, Bonifazi, M, Gasparini, S, Mei, F, Cerutti, E, Lacedonia, D, Santoro, A, Guidelli, G, Greco, S, Castellan, A, Infantino, G, Camici, L, Frigieri, F, Pavoni, V, Migliori, L, Rossetti, B, Montagnini, F, Mauro, I, Genovese, E, Capuozzo, A, Vitiello, L, Sirignano, E, Gnesin, P, Servillo, G, Marinelli, A, Pasero, D, Casadio, L, Babudieri, S, Madeddu, G, De Vito, A, Ranghitta, M, Passalacqua, R, Antonio, F, Gentile, I, Buonomo, A, Scotto, R, Zappulo, E, Dell'Aquila, G, Bianchetti, A, Guerini, F, Vallone, A, Oppedisano, P, Pusterla, L, Giglio, O, Sartori, E, Zanardini, C, Gatti, P, Vincenzo, V, Piconi, S, Molteni, C, Dognini, G, Cosimo, F, Guarneri, L, Pulvirenti, F, Mondino, V, Traballi, G, Iemoli, E, Grisolia, A, Giorgi, R, Nucera, G, Raffaelli, V, Marino, P, Negro, E, Serati, L, Silvia, T, Iacobello, C, Strano, G, Boglione, L, Catania, A, Gipponi, P, Di Cato, L, Panaccione, A, Vitale, G, Crippa, I, Giacomini, M, Basile, A, Andrea, B, Tundo, P, Buzzigoli, S, Palmiero, G, Magnaca, A, Silva, M, Crespi, S, Pasquino, B, Consales, G, Bragantini, D, Mastroianni, F, Righetti, G, Scarafino, A, Bitetto, M, Franzetti, F, Piga, S, Delmonte, V, Carbonara, S, Losappio, R, Dejaco, C, Del Bono, V, Gilioli, F, Barzan, D, De Struppi, S, Carlotto, A, Guadagnin, M, Girardis, M, Bertellini, E, Dentali, F, Foresta, G, Baratta, A, Viviani, R, Agrati, A, Perego, G, Montineri, A, Manuele, R, Bonfante, S, Aquilini, D, Prozzo, A, Santopuoli, D, Di Rosa, Z, Alborghetti, A, Peci, P, Bakhtadze, N, Pandini, C, Ashofarir, N, Casella, G, Spagnolli, W, Urru, S, Marchesoni, I, Caminiti, G, Argilloni, E, Danieli, E, Ghirardi, G, Antonioli, C, Lipari, A, Zavarise, P, Kokaly, F, Polati, E, Gottin, L, Lucernoni, P, De Conti, F, Marcon, E, Pontali, E, Vacca, E, Saffioti, C, Zunino, A, Pognuz, E, Berlot, G, Saltori, M, Tedesco, A, Agostini, C, Di Rosolini, M, Marino, F, Bellinzona, G, Grassi, W, Di Carlo, M, Scimonello, G, Nonini, S, Mondino, M, Mantovani, L, Tenti, E, Tropea, C, Di Stefano, D, Guelfi, P, Dagna, L, Morgana, G, Montemurro, L, Girelli, D, Crisafulli, E, Maroccia, A, Cemuschi, A, Bernasconi, M, Zummo, U, Barbato, V, Bevilacqua, S, Buonfanti, G, Canzanella, G, De Matteis, G, Florio, M, Martino, M, Ribecco, M, Romano, F, Savio, A, Sparavigna, L, Curvietto, M, Citarella, M, Nava, V, Maggioni, P, Magni, M, Iommelli, C, Bianco, A, Corsini, R, Valli, L, Ruggieri, M, Mancini, A, Melica, T, Ferrari, A, Cicognini, D, Delliponti, M, Zuccarini, A, Ciani, S, Raffaeli, D, Donati, L, Cannizzo, S, Lui, S, Santini, L, Roncaglia, E, Mighali, P, Eisendle, F, Cerino, G, Citterio, C, Di Nunzio, C, Lamonica, S, Resimini, S, Sarteschi, G, Pavei, C, Battistini, N, Gazzola, E, Miceli, M, Pontiggia, S, Lonati, V, Giannandrea, G, Sortino, C, Ravani, S, Uggeri, C, Jocolle, G, Bare, C, Baroni, I, De Candia, D, Fiorini, B, Chierico, K, Romeo, F, Bottega, R, Boccasile, L, Corsaro, A, Spadoni, C, Ria, E, Chiari, S, Ercolino, G, Dell'Uomo, V, Viri, S, Minato, M, Gazzola, L, Dorina, B, Gianelli, D, Maspero, S, Farinazzo, M, Zanini, P, Sangiovanni, A, Del Giudice, A, Dragonetti, M, Bordignon, S, Machiavelli, A, Chiodelli, G, Spatarella, M, Zenoni, D, Beretta, F, Santilli, G, Badagliacca, R, Angileri, M, Giannelli, L, Campomori, A, Maimone, P, Fadda, A, Faoro, S, Pisterna, A, Cacopardo, B, Marino, A, Pampaloni, A, Celesia, B, Cinnella, G, Labella, D, Caporusso, R, Danzi, M, Fiscon, M, Malena, M, Fendt, D, Nardi, S, Stobbione, P, Savi, M, De Monte, A, Scala, A, Liberato, N, Luchi, S, Vincenti, A, Cabrini, L, Pinelli, G, Brugioni, L, Potenza, D, Numis, F, Porta, G, D'Amico, M, Iengo, B, Angarano, G, Saracino, A, Blasi, L, De Negri, P, Angelici, S, Farina, A, Martino, G, Bitti, G, Tedeschi, A, De Ponti, S, Agostinone, A, Parruti, G, Consorte, A, Frattari, A, Filippelli, A, Pagliano, P, Masullo, A, Sellitto, C, Reta, M, Rossi, N, Raumer, L, Andreassi, S, Brancaleoni, P, Carai, A, Salerno, A, Marinangeli, F, Mariani, R, Ciccone, A, Meschini, C, Santoboni, G, Angrisani, C, Micarelli, D, Tarquini, G, Fregoni, V, Volta, C, Cherubini, A, Del Prete, M, Ciarrochi, E, Tasca, F, Ballarin, A, Bianchin, A, Flocco, R, Cuzzone, V, Carpinteri, M, Gallotti, P, Torre, F, Zannetti, P, Crapis, M, Venturini, S, Barattini, M, Gori, G, Mastroianni, A, De Stefano, G, Gilio, M, Rapisarda, G, Gulisano, L, Granata, M, Saglimbene, S, Montalto, M, Grasso, I, De Luca, S, Magro, G, Messina, F, Scapino, B, Abrate, P, Francisco, C, Pesce, L, Navarra, M, Agosti, M, Pagani, S, Piluso, M, Ricioppo, A, Tognella, S, Rovere, P, Vincenzi, M, Ghirardi, L, Generali, D, Ingrosso, M, Desiderio, E, Molaro, R, Vitiello, S, Lancione, L, Paone, T, Meli, A, Mainardi, S, Rastellino, V, Ursillo, A, Grigoli, P, Bovetto, E, Stefanetto, I, Mazzola, F, Daniele, A, Bisio, C, Delnero, P, Morando, G, Nava, A, Francesco, L, Fiammengo, F, Regis, M, Roccatello, D, Sabato, E, Liccardi, M, Bretto, C, Lutri, L, Castenetto, E, Roberti, G, Guidi, M, Bini, F, Zappa, M, Trequattrini, T, Rivitti, R, Vigliarolo, R, Succu, A, Lilli, M, Serao, M, Giogre, G, Ruggieri, A, Flores, K, Vairo, G, Satira, R, Lingua, A, Spina, R, Nicastri, E, Maffongelli, G, Barreca, F, Scollet, S, Franchi, F, Fabbri, C, Minuz, P, Dalbeni, A, Zanatta, P, Gelormini, D, Mandelli, A, Galderisi, F, Zoia, E, Marchi, M, Neves, N, Carbone, G, Di Caterino, E, Petrone, A, Usai, C, Bandiera, F, Monti, R, Hofer, A, Castiglione, G, Angeletti, C, Tarsia, P, Veronese, L, Artoni, P, Larussa, D, Fumagalli, R, Brioschi, P, Cerutti, A, Pasquino, P, Gilberto, F, Cantadori, L, Coppola, N, Spolveri, S, Pollastri, C, Fico, L, Principi, T, Pierantozzi, S, Fontana, C, Lubrano, G, Martinelli, L, Navalesi, P, Serra, E, Cogi, E, Manzi, A, Furino, E, Dasseni, N, Gentilini, C, Benatti, E, Pignatti, A, Aiello, G, Milia, M, Covesnon, M, Brianti, A, Francesco, C, Ilaria, B, Pagnozzi, F, Mietta, S, Rossi, A, Maroni, L, Borroni, V, Bellintani, C, Sgarabotto, C, Bizzotto, G, Bucci, L, Spagnuolo, G, Agostini, M, Caria, F, Testa, F, De Palma, R, Murdaca, G, Zanolini, G, Sala, N, Righini, E, Pontremoli, R, Aondio, G, Riccardi, F, De Cristoforo, M, De Michele, F, Storti, A, Perra, R, Deidda, S, Enrica, C, Valastro, F, Pierfranceschi, M, De Gennaro, F, Nardecchia, A, Castellini, M, Buetto, G, Ippoliti, G, Sicheri, D, Bottoli, M, De Arroyabe, B, Versaci, A, Pallotti, G, Civita, M, Grio, M, Liuzzi, N, Molino, P, Pastorelli, M, Ricchiardi, A, Varbella, F, Zeme, A, Sighieri, C, Portale, G, Olivetti, A, Pagnoni, C, Moschini, G, Boni, S, Guerra, A, Scudellari, R, Vella, S, Inchiostro, S, Piazza, O, Guarino, S, Aldegheri, G, Napoli, G, Morettini, A, Caldini, E, Menicacci, L, Pieralli, F, Torrini, M, Poggesi, L, Visetti, E, Mangano, C, Visconti, S, Maietta, P, Banfi, E, Cartella, S, Venturi, B, Nuceri, A, Chiesa, E, Pacentra, E, Panzolato, G, Giannotti, M, Bianchi, C, Pietrangelo, A, Para, O, Rutili, M, Russo, R, Lanfranco, M, Scalabrino, E, Tafuri, A, Chiarello, T, Perfetti, E, Cancanelli, L, Otero, M, Pannella, G, Bellucci, F, Ferrero, G, Vico, C, Stillante, M, D'Andrea, G, Amoroso, F, Arcidiacono, A, Bella, A, Belsito, A, Berte, Y, Carubia, G, Caruso, M, Casella, O, Chiereleson, F, Costa, C, De Franco, D, Germana, G, Messina, A, Musumeci, D, Noto, C, Valenti, M, Sorrentino, C, Panico, R, Schettino, G, Piccoli, J, Pepe, A, Ottaviano, M, Marrazzo, G, Raponi, G, Diberardino, S, Bausi, S, Marini, S, Giubellino, E, Innocenti, G, Gugliemi, G, Maccari, D, Baciu, I, Perrone F., Piccirillo M. C., Ascierto P. A., Salvarani C., Parrella R., Marata A. M., Popoli P., Ferraris L., Marrocco-trischitta M. M., Ripamonti D., Binda F., Bonfanti P., Squillace N., Castelli F., Muiesan M. L., Lichtner M., Calzetti C., Salerno N. D., Atripaldi L., Cascella M., Costantini M., Dolci G., Facciolongo N. C., Fraganza F., Massari M., Montesarchio V., Mussini C., Negri E. A., Botti G., Cardone C., Gargiulo P., Gravina A., Schettino C., Arenare L., Chiodini P., Gallo C., Vitale M. G., Trojaniello C., Palla M., Bianchi A. A. M., De Feo G., Miscio L., Froldi M., Menicanti L., Cuppone M. T., Gobbo G., Baldessari C., Valenti V., Castelvecchio S., Poli F., Giacomazzi F., Piccinni R., Annnunziata M. L., Biondi A., Bussolari C., Mazzoleni M., Giachi A., Filtz A., Manini A., Poletti E., Masserini F., Conforti F., Gaudiano G., Favero V., Moroni A., Viva T., Fancoli F., Ferrari D., Niro D., Resta M., Ballotta A., Poli M. D., Ranucci M., Tebaldi A., Gritti G., Pasulo L., Gaglio L., Del Fabbro R., Alborghetti L., Giustinetti G., Columpsi P., Cazzaniga M., Capici S., Sala L., Di Sciacca R., Mosca G., Pirozzi M. R., Franceschini F., Roccaro A., Salvetti M., Paini A., Corda L., Ricci C., Tomasoni L., Nasta P., Lorenzotti S., Odolini S., Foca E., Roldan E. Q., Metra M., Magrini S., Borghetti P., Latronico N., Piva S., Filippini M., Tomasoni G., Zuccala F., Cattaneo S., Scolari F., Bossini N., Gaggiotti M., Properzi M., Del Giudice E., Marocco R., Carraro A., Del Borgo C., Belvisi V., Tieghi T., De Masi M., Zuccala P., Fabietti P., Vetica A., Mercurio V. S., Fondaco L., Kertusha B., Curtolo A., Lubrano R., Zotti M. G., Puorto A., Ciuffreda M., Sarni A., Monteforte G., Romeo D., Viola E., Damiani C., Barone A., Mantovani B., Di Sanzo D., Gentili V., Carletti M., Aiuti M., Gallo A., Meliante P. G., Martellucci S., Riggio O., Cardinale V., Ridola L., Bragazzi M. 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B., Montineri A., Manuele R., Bonfante S., Aquilini D., Prozzo A., Santopuoli D., Di Rosa Z., Alborghetti A., Peci P., Bakhtadze N., Pandini C. S., Ashofarir N., Casella G., Spagnolli W., Urru S., Marchesoni I., Caminiti G., Argilloni E., Danieli E., Ghirardi G., Antonioli C. M., Lipari A., Zavarise P., Kokaly F., Polati E., Gottin L., Lucernoni P., De Conti F., Marcon E., Pontali E., Vacca E. B., Saffioti C., Zunino A., Pognuz E. R., Berlot G., Saltori M., Tedesco A., Agostini C., Di Rosolini M. A., Marino F., Bellinzona G., Grassi W., Di Carlo M., Scimonello G., Nonini S., Mondino M., Mantovani L. F., Tenti E., Tropea C. M. G., Di Stefano D. E., Guelfi P., Dagna L., Morgana G., Montemurro L., Girelli D., Crisafulli E., Maroccia A., Cemuschi A. M., Bernasconi M., Zummo U., Barbato V., Bevilacqua S., Buonfanti G., Canzanella G., De Matteis G., Florio M., Martino M., Ribecco M. T., Romano F., Savio A., Sparavigna L., Curvietto M., Citarella M., Nava V., Maggioni P., Magni M., Iommelli C., Bianco A., Corsini R., Valli L., Ruggieri M. P., Mancini A., Melica T., Ferrari A., Cicognini D., Delliponti M., Zuccarini A., Ciani S., Raffaeli D., Donati L., Cannizzo S., Lui S., Santini L., Roncaglia E., Mighali P., Eisendle F., Cerino G., Citterio C., Di Nunzio C., Lamonica S., Resimini S., Sarteschi G., Pavei C., Battistini N., Gazzola E., Miceli M., Pontiggia S., Lonati V., Giannandrea G., Sortino C., Ravani S., Uggeri C., Jocolle G., Bare C., Baroni I., De Candia D., Fiorini B., Chierico K., Romeo F., Bottega R., Boccasile L., Corsaro A., Spadoni C., Ria E., Chiari S., Ercolino G., Dell'uomo V., Viri S., Minato M., Gazzola L., Dorina B., Gianelli D., Maspero S., Farinazzo M., Zanini P., Sangiovanni A., Del Giudice A., Dragonetti M. M., Bordignon S., Machiavelli A. M., Chiodelli G., Spatarella M., Zenoni D., Beretta F. N., Santilli G., Badagliacca R., Angileri M., Giannelli L., Campomori A., Maimone P., Fadda A., Faoro S., Pisterna A., Cacopardo B., Marino A., Pampaloni A., Celesia B. M., Cinnella G., Labella D., Caporusso R. R., Danzi M., Fiscon M., Malena M., Fendt D., Nardi S., Stobbione P., Savi M. L., De Monte A., Scala A., Liberato N. L., Luchi S., Vincenti A., Cabrini L., Pinelli G., Brugioni L., Potenza D., Numis F. G., Porta G., D'amico M., Iengo B., Angarano G., Saracino A., Blasi L., De Negri P., Angelici S., Farina A., Martino G. P., Bitti G., Tedeschi A., De Ponti S., Agostinone A., Parruti G., Consorte A., Frattari A., Filippelli A., Pagliano P., Masullo A., Sellitto C., Reta M., Rossi N., Raumer L., Andreassi S., Brancaleoni P., Carai A., Salerno A. M., Marinangeli F., Mariani R., Ciccone A., Meschini C., Santoboni G., Angrisani C., Micarelli D., Tarquini G., Fregoni V., Volta C. A., Cherubini A., Del Prete M. S., Ciarrochi E., Tasca F., Ballarin A., Bianchin A., Flocco R., Cuzzone V., Carpinteri M., Gallotti P., Torre F., Zannetti P., Crapis M., Venturini S., Barattini M., Gori G., Mastroianni A., De Stefano G., Gilio M., Rapisarda G., Gulisano L., Granata M. L., Saglimbene S., Montalto M. T., Grasso I., De Luca S., Magro G., Messina F., Scapino B., Abrate P., Francisco C., Pesce L., Navarra M., Agosti M., Pagani S., Piluso M., Ricioppo A., Tognella S., Rovere P., Vincenzi M., Ghirardi L., Generali D., Ingrosso M., Desiderio E., Molaro R., Vitiello S., Lancione L., Paone T. C., Meli A., Mainardi S., Rastellino V., Ursillo A., Grigoli P. D., Bovetto E., Stefanetto I. M., Mazzola F., Daniele A., Bisio C., Delnero P., Morando G., Nava A., Francesco L., Fiammengo F., Regis M., Roccatello D., Sabato E., Liccardi M. M., Bretto C., Lutri L., Castenetto E., Roberti G., Guidi M. F., Bini F., Zappa M. C., Trequattrini T., Rivitti R., Vigliarolo R., Succu A., Lilli M., Serao M., Giogre G., Ruggieri A., Flores K., Vairo G., Satira R., Lingua A., Spina R., Nicastri E., Maffongelli G., Barreca F., Scollet S., Franchi F., Fabbri C., Minuz P., Dalbeni A., Zanatta P., Gelormini D., Mandelli A., Galderisi F., Zoia E., Marchi M. R., Neves N. D. A., Carbone G., Di Caterino E., Petrone A., Usai C. A., Bandiera F., Monti R., Hofer A., Castiglione G., Angeletti C., Tarsia P., Veronese L., Artoni P. D., Larussa D., Fumagalli R., Brioschi P., Cerutti A., Pasquino P., Gilberto F., Cantadori L., Tomasoni L. R., Coppola N., Spolveri S., Pollastri C., Fico L., Principi T., Pierantozzi S., Fontana C. C., Lubrano G., Martinelli L., Navalesi P., Serra E., Cogi E., Manzi A., Furino E., Dasseni N., Gentilini C., Benatti E., Pignatti A., Aiello G., Milia M., Covesnon M. G., Brianti A., Francesco C., Ilaria B., Pagnozzi F., Mietta S., Rossi A., Maroni L., Borroni V., Bellintani C., Sgarabotto C., Bizzotto G., Bucci L., Spagnuolo G., Agostini M., Caria F. C., Testa F., De Palma R., Murdaca G., Zanolini G., Sala N., Righini E., Pontremoli R., Aondio G., Riccardi F., De Cristoforo M. G., De Michele F., Storti A., Perra R., Deidda S., Enrica C., Valastro F., Pierfranceschi M. G., De Gennaro F., Nardecchia A. L., Castellini M., Buetto G., Ippoliti G., Sicheri D., Bottoli M. G., De Arroyabe B. M. L., Versaci A., Pallotti G., Civita M., Grio M., Liuzzi N., Molino P., Pastorelli M., Ricchiardi A., Varbella F., Zeme A. D., Sighieri C., Portale G., Olivetti A., Pagnoni C., Moschini G., Boni S., Guerra A., Scudellari R., Vella S., Inchiostro S., Piazza O., Guarino S., Aldegheri G., Napoli G., Morettini A., Caldini E., Menicacci L., Pieralli F., Torrini M., Poggesi L., Visetti E. M., Mangano C., Visconti S., Maietta P., Banfi E., Cartella S., Venturi B., Nuceri A., Chiesa E., Pacentra E., Panzolato G., Giannotti M., Bianchi C., Pietrangelo A., Para O., Rutili M. S., Russo R., Lanfranco M., Scalabrino E., Tafuri A., Chiarello T., Perfetti E., Cancanelli L., Otero M., Pannella G., Bellucci F., Ferrero G., Vico C., Stillante M. S., D'andrea G., Amoroso F., Arcidiacono A., Bella A. M., Belsito A., Berte Y., Carubia G., Caruso M. G., Casella O., Chiereleson F., Costa C., De Franco D., Germana G., Messina A., Musumeci D., Noto C., Valenti M., Sorrentino C., Panico R., Schettino G., Piccoli J., Pepe A., De Rosa F., Ottaviano M., Marrazzo G., Raponi G., Diberardino S., Bausi S., Marini S. F., Giubellino E., Innocenti G., Gugliemi G., Maccari D., Baciu I., Perrone, F, Piccirillo, M, Ascierto, P, Salvarani, C, Parrella, R, Marata, A, Popoli, P, Ferraris, L, Marrocco-trischitta, M, Ripamonti, D, Binda, F, Bonfanti, P, Squillace, N, Castelli, F, Muiesan, M, Lichtner, M, Calzetti, C, Salerno, N, Atripaldi, L, Cascella, M, Costantini, M, Dolci, G, Facciolongo, N, Fraganza, F, Massari, M, Montesarchio, V, Mussini, C, Negri, E, Botti, G, Cardone, C, Gargiulo, P, Gravina, A, Schettino, C, Arenare, L, Chiodini, P, Gallo, C, Vitale, M, Trojaniello, C, Palla, M, Bianchi, A, De Feo, G, Miscio, L, Froldi, M, Menicanti, L, Cuppone, M, Gobbo, G, Baldessari, C, Valenti, V, Castelvecchio, S, Poli, F, Giacomazzi, F, Piccinni, R, Annnunziata, M, Biondi, A, Bussolari, C, Mazzoleni, M, Giachi, A, Filtz, A, Manini, A, Poletti, E, Masserini, F, Conforti, F, Gaudiano, G, Favero, V, Moroni, A, Viva, T, Fancoli, F, Ferrari, D, Niro, D, Resta, M, Ballotta, A, Poli, M, Ranucci, M, Tebaldi, A, 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D., Negro C., Converso M., Bosco F., Amadasi S., Prandini P., Cocchi S., Manfrin V., Del Punta V., Mazzola G., Sportato G., Romagnoli M., Cristini F., Facondini F., Perin T., Boschi A., Meschiari M., Guaraldi G., Modica S., Moneta S., Boccalatte D., Marchetti V., Ebbreo G., Dale M., Tura P., Rizzoni D., Boari G. E. M., Bonetti S., Marini E., Daniele I., Grossi P. A., Delfrate N. W., Bernhart O., Spizzo G., Mahlknecht K., Volkl T., Di Pietro M. A., Trezzi M., Monacci C., Peris A., Bonizzoli M., Cavanna L., Moroni C., Stroppa E. M., Savio M. C., Gatti F., Bartolaminelli C., Petrosillo N., Donno D. R., Taglietti F., Topino S., Chinello P., Galati V., D'offizi G., Taibi C., Cimolato B., Moroni F., Palagano N., Pelagatti L., Cristiana S., Landini G., Amitrano M., Raimondo M., Mangiacapra S., Romano A., Atteno M., Blanc P., Suardi L. R., Pallotto C., Casinelli K., Uccella I., Harari S., Caminati A., Lipani F., Di Perri G., Calcagno A., Calleri G., Montrucchio C., Caputo A. M., Cozzio S., Donne L. D., Bassetti M., Malgorzata M., Nicolini L. A., Russo C., Sepulcri C., Beltramini S., Mina F., Puoti M., Gandino A., Langer T., D'amico F., Rocchetti C., Cettolo F., Gabriele F., Bocchi P., Cioni G., Cappi C., Corcione S., De Rosa F. G., Scabini S., Canta F., Pinna S. M., Pensa A., Rocco M., Cirasa M. T., Spinicci M., Mencarini J., Zammarchi L., Giovanni C., Sciole K., Bassi F., Bianchi M., Frigerio S., Spaziani S., Nucera A., Rizzardini G., Cossu M. V., Antivalle M., Carpinteri G., Macheda S., Labate D., Bottiroli M., Erne E. M., Cristina Z., Di Biase V., Malberti F., Montani G., Poisa P., Bettini D., Cauda R., Ciccullo A., Riccardi N., Angheben A., Turrini M., Clerici R., Gardellini A., Liparulo L., Rossini T., Ucciferri C., Cipollone F., Vecchiet J., Nico A., Marra L., Leone A., Sdanganelli A., Palmiotti G. A., D'alagni G., Santantonio T. A., Caputo S. L., Bottalico I., Ponticiello A., Di Perna F., Bernardi E., Beltrame A., Bravi S., David M., Bernardi P., Galante D., Uccelli M. C., Prestini K., Drera M., Zini E., Peregrinelli A., Blanzuoli L., Benedetti V., Calvi R., Scaglione N., Nallino G., Bonazzi M., Crespi T., Masolin T., Regazzetti A., Cerri M. C., Maffezzini E., Piazza M., Papetti C., Filippi C. D., Roveda E., Cipolla G., Scozzafava M., Crepaldi M., Henchi S., Vanoni N., Repossi A., Vezzoli M., Scorletti E., Perugini O., Pasini S. M., Pacetti V., Ferrari L., de Paduanis G. A., Del Duca S., Dell'ara F., Brocchieri A., Minoja G., Storti E., Pitagora L., Costa I., Delfanti F., Orlandi M., Ruggeri R., Ruggieri L., Livigni S., Silengo D., Ageno W., Pedrini L., Artiol S., Morbidoni L., De Donno G., Ravagnani V., Inglese F., Scotton P. G., Costantini P., Delucchi M., Clini E., Ansuini A., Marco B., Giuseppe L., Vincenzo B., Rastelli G., Doria A., Vianello A., Cattelan A. M., Bindoli S., Felicietti M., Canetta C., Scartabellati A., Accordino S., Ferrara M., Cocco L., Cirillo F., Pace E., De Caro M., Alberico M., Benigni G., Damiano T., Fusco P., Iuorio A., Torretta G., Racagni M., Muttini S., Sala G., Ghiringhelli P., Chiumiento F., Baccari L., Luca B., Bocchi F., Benatti F., Catellani J., Coppola M., Papi A., Bosco E., Lazzeri C., Cesira N., Puttini C., Carli T., Croci L., Corridi M., Arlotti M., Guerrini G., Cola L., Romanelli M., Bonifazi M., Gasparini S., Mei F., Cerutti E., Lacedonia D., Santoro A., Guidelli G. M., Greco S., Castellan A., Infantino G., Camici L., Frigieri F. C., Pavoni V., Migliori L., Rossetti B., Montagnini F., Mauro I., Genovese E., Capuozzo A., Vitiello L., Sirignano E., Gnesin P., Servillo G., Marinelli A., Pasero D., Casadio L., Babudieri S., Madeddu G., De Vito A., Ranghitta M., Passalacqua R., Antonio F., Gentile I., Buonomo A. R., Scotto R., Zappulo E., Dell'aquila G., Bianchetti A., Guerini F., Vallone A., Oppedisano P., Pusterla L., Giglio O., Sartori E., Zanardini C., Gatti P., Vincenzo V., Piconi S., Molteni C., Dognini G., Cosimo F., Guarneri L., Pulvirenti F., Mondino V., Traballi G., Iemoli E., Grisolia A., Giorgi R., Nucera G., Raffaelli V., Marino P., Negro E., Serati L., Silvia T., Iacobello C., Strano G., Boglione L., Catania A., Gipponi P., Di Cato L., Panaccione A., Vitale G., Crippa I. A., Giacomini M., Basile A., Andrea B., Tundo P., Buzzigoli S., Palmiero G., Magnaca A., Silva M., Ricci M., Crespi S., Pasquino B., Consales G., Bragantini D., Mastroianni F., Righetti G., Scarafino A., Bitetto M., Franzetti F., Piga S., Delmonte V., Carbonara S., Losappio R., Dejaco C., Mastroianni C., Del Bono V., Gilioli F., Barzan D., De Struppi S., Carlotto A., Guadagnin M. L., Girardis M., Bertellini E., Dentali F., Foresta G., Baratta A., Viviani R., Agrati A. M., Perego G. B., Montineri A., Manuele R., Bonfante S., Aquilini D., Prozzo A., Santopuoli D., Di Rosa Z., Alborghetti A., Peci P., Bakhtadze N., Pandini C. S., Ashofarir N., Casella G., Spagnolli W., Urru S., Marchesoni I., Caminiti G., Argilloni E., Danieli E., Ghirardi G., Antonioli C. M., Lipari A., Zavarise P., Kokaly F., Polati E., Gottin L., Lucernoni P., De Conti F., Marcon E., Pontali E., Vacca E. B., Saffioti C., Zunino A., Pognuz E. R., Berlot G., Saltori M., Tedesco A., Agostini C., Di Rosolini M. A., Marino F., Bellinzona G., Grassi W., Di Carlo M., Scimonello G., Nonini S., Mondino M., Mantovani L. F., Tenti E., Tropea C. M. G., Di Stefano D. E., Guelfi P., Dagna L., Morgana G., Montemurro L., Girelli D., Crisafulli E., Maroccia A., Cemuschi A. M., Bernasconi M., Zummo U., Barbato V., Bevilacqua S., Buonfanti G., Canzanella G., De Matteis G., Florio M., Martino M., Ribecco M. T., Romano F., Savio A., Sparavigna L., Curvietto M., Citarella M., Nava V., Maggioni P., Magni M., Iommelli C., Bianco A., Corsini R., Valli L., Ruggieri M. P., Mancini A., Melica T., Ferrari A., Cicognini D., Delliponti M., Zuccarini A., Ciani S., Raffaeli D., Donati L., Cannizzo S., Lui S., Santini L., Roncaglia E., Mighali P., Eisendle F., Cerino G., Citterio C., Di Nunzio C., Lamonica S., Resimini S., Sarteschi G., Pavei C., Battistini N., Gazzola E., Miceli M., Pontiggia S., Lonati V., Giannandrea G., Sortino C., Ravani S., Uggeri C., Jocolle G., Bare C., Baroni I., De Candia D., Fiorini B., Chierico K., Romeo F., Bottega R., Boccasile L., Corsaro A., Spadoni C., Ria E., Chiari S., Ercolino G., Dell'uomo V., Viri S., Minato M., Gazzola L., Dorina B., Gianelli D., Maspero S., Farinazzo M., Zanini P., Sangiovanni A., Del Giudice A., Dragonetti M. M., Bordignon S., Machiavelli A. M., Chiodelli G., Spatarella M., Zenoni D., Beretta F. N., Santilli G., Badagliacca R., Angileri M., Giannelli L., Campomori A., Maimone P., Fadda A., Faoro S., Pisterna A., Cacopardo B., Marino A., Pampaloni A., Celesia B. M., Cinnella G., Labella D., Caporusso R. R., Danzi M., Fiscon M., Malena M., Fendt D., Nardi S., Stobbione P., Savi M. L., De Monte A., Scala A., Liberato N. L., Luchi S., Vincenti A., Cabrini L., Pinelli G., Brugioni L., Potenza D., Numis F. G., Porta G., D'amico M., Iengo B., Angarano G., Saracino A., Blasi L., De Negri P., Angelici S., Farina A., Martino G. P., Bitti G., Tedeschi A., De Ponti S., Agostinone A., Parruti G., Consorte A., Frattari A., Filippelli A., Pagliano P., Masullo A., Sellitto C., Reta M., Rossi N., Raumer L., Andreassi S., Brancaleoni P., Carai A., Salerno A. M., Marinangeli F., Mariani R., Ciccone A., Meschini C., Santoboni G., Angrisani C., Micarelli D., Tarquini G., Fregoni V., Volta C. A., Cherubini A., Del Prete M. S., Ciarrochi E., Tasca F., Ballarin A., Bianchin A., Flocco R., Cuzzone V., Carpinteri M., Gallotti P., Torre F., Zannetti P., Crapis M., Venturini S., Barattini M., Gori G., Mastroianni A., De Stefano G., Gilio M., Rapisarda G., Gulisano L., Granata M. L., Saglimbene S., Montalto M. T., Grasso I., De Luca S., Magro G., Messina F., Scapino B., Abrate P., Francisco C., Pesce L., Navarra M., Agosti M., Pagani S., Piluso M., Ricioppo A., Tognella S., Rovere P., Vincenzi M., Ghirardi L., Generali D., Ingrosso M., Desiderio E., Molaro R., Vitiello S., Lancione L., Paone T. C., Meli A., Mainardi S., Rastellino V., Ursillo A., Grigoli P. D., Bovetto E., Stefanetto I. M., Mazzola F., Daniele A., Bisio C., Delnero P., Morando G., Nava A., Francesco L., Fiammengo F., Regis M., Roccatello D., Sabato E., Liccardi M. M., Bretto C., Lutri L., Castenetto E., Roberti G., Guidi M. F., Bini F., Zappa M. C., Trequattrini T., Rivitti R., Vigliarolo R., Succu A., Lilli M., Serao M., Giogre G., Ruggieri A., Flores K., Vairo G., Satira R., Lingua A., Spina R., Nicastri E., Maffongelli G., Barreca F., Scollet S., Franchi F., Fabbri C., Minuz P., Dalbeni A., Zanatta P., Gelormini D., Mandelli A., Galderisi F., Zoia E., Marchi M. R., Neves N. D. A., Carbone G., Di Caterino E., Petrone A., Usai C. A., Bandiera F., Monti R., Hofer A., Castiglione G., Angeletti C., Tarsia P., Veronese L., Artoni P. D., Larussa D., Fumagalli R., Brioschi P., Cerutti A., Pasquino P., Gilberto F., Cantadori L., Tomasoni L. R., Coppola N., Spolveri S., Pollastri C., Fico L., Principi T., Pierantozzi S., Fontana C. C., Lubrano G., Martinelli L., Navalesi P., Serra E., Cogi E., Manzi A., Furino E., Dasseni N., Gentilini C., Benatti E., Pignatti A., Aiello G., Milia M., Covesnon M. 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M., Mangano C., Visconti S., Maietta P., Banfi E., Cartella S., Venturi B., Nuceri A., Chiesa E., Pacentra E., Panzolato G., Giannotti M., Bianchi C., Pietrangelo A., Para O., Rutili M. S., Russo R., Lanfranco M., Scalabrino E., Tafuri A., Chiarello T., Perfetti E., Cancanelli L., Otero M., Pannella G., Bellucci F., Ferrero G., Vico C., Stillante M. S., D'andrea G., Amoroso F., Arcidiacono A., Bella A. M., Belsito A., Berte Y., Carubia G., Caruso M. G., Casella O., Chiereleson F., Costa C., De Franco D., Germana G., Messina A., Musumeci D., Noto C., Valenti M., Sorrentino C., Panico R., Schettino G., Piccoli J., Pepe A., De Rosa F., Ottaviano M., Marrazzo G., Raponi G., Diberardino S., Bausi S., Marini S. F., Giubellino E., Innocenti G., Gugliemi G., Maccari D., and Baciu I.
- Abstract
Background: Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods: A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results: In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P = 0.52) and 22.4% (97.5% CI: 17.2-28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions: Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).
- Published
- 2020
5. Correction to: Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial (Journal of Translational Medicine, (2020), 18, 1, (405), 10.1186/s12967-020-02573-9)
- Author
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Perrone, F., Piccirillo, M. C., Ascierto, P. A., Salvarani, C., Parrella, R., Marata, A. M., Popoli, P., Ferraris, L., Marrocco-Trischitta, M. M., Ripamonti, D., Binda, F., Bonfanti, P., Squillace, N., Castelli, F., Muiesan, M. L., Lichtner, M., Calzetti, C., Salerno, N. D., Atripaldi, L., Cascella, M., Costantini, M., Dolci, G., Facciolongo, N. C., Fraganza, F., Massari, M., Montesarchio, V., Mussini, C., Negri, E. A., Botti, G., Cardone, C., Gargiulo, P., Gravina, A., Schettino, C., Arenare, L., Chiodini, P., Gallo, C., Vitale, M. G., Trojaniello, C., Palla, M., Bianchi, A. A. M., De Feo, G., Miscio, L., Chiodiniy, P., Froldi, M., Menicanti, L., Cuppone, M. T., Gobbo, G., Baldessari, C., Valenti, V., Castelvecchio, S., Poli, F., Giacomazzi, F., Piccinni, R., Annnunziata, M. L., Biondi, A., Bussolari, C., Mazzoleni, M., Giachi, A., Filtz, A., Manini, A., Poletti, E., Masserini, F., Conforti, F., Gaudiano, G., Favero, V., Moroni, A., Viva, T., Fancoli, F., Ferrari, D., Niro, D., Resta, M., Ballotta, A., Poli, M. D., Ranucci, M., Tebaldi, A., Gritti, G., Pasulo, L., Gaglio, L., Del Fabbro, R., Alborghetti, L., Giustinetti, G., Columpsi, P., Cazzaniga, M., Capici, S., Sala, L., Di Sciacca, R., Mosca, G., Pirozzi, M. R., Franceschini, F., Roccaro, A., Salvetti, M., Paini, A., Corda, L., Ricci, C., Tomasoni, L., Nasta, P., Lorenzotti, S., Odolini, S., Foca, E., Roldan, E. Q., Metra, M., Magrini, S., Borghetti, P., Latronico, N., Piva, S., Filippini, M., Tomasi, G., Zuccala, F., Cattaneo, S., Scolari, F., Bossini, N., Gaggiotti, M., Properzi, M., Del Borgo, C., Marocco, R., Belvisi, V., Tieghi, T., De Masi, M., Zuccala, P., Fabietti, P., Vetica, A., Mercurio, V. S., Carraro, A., Fondaco, L., Kertusha, B., Curtolo, A., Del Giudice, E., Lubrano, R., Zotti, M. G., Puorto, A., Ciuffreda, M., Sarni, A., Monteforte, G., Romeo, D., Viola, E., Damiani, C., Barone, A., Mantovani, B., Di Sanzo, D., Gentili, V., Carletti, M., Aiuti, M., Gallo, A., Meliante, P. G., Martellucci, S., Riggio, O., Cardinale, V., Ridola, L., Bragazzi, M. C., Gioia, S., Valenzi, E., Graziosi, C., Bina, N., Fasolo, M., Ricci, S., Gioacchini, M. T., Lucci, A., Corso, L., Tornese, D., Nijhawan, P., Equitani, F., Cosentino, C., Palladino, M., Leonetti, F., Leto, G., Gnessi, C., Campagna, G., Cesareo, R., Marrocco, F., Straface, G., Mecozzi, A., Cerbo, L., Isgro, V., Parrocchia, S., Visconti, G., Casati, G., Ariani, A., Donghi, L., Tacconelli, E., Bertoldi, M., Cattaneo, P., Lambertenghi, L., Motta, L., Omega, L., Albano, G., Scarano, F., De Rosa, A., Buglione, A., Lavoretano, S., Gaglione, G., De Marco, M., Sangiovanni, V., Fusco, F. M., Viglietti, R., Manzillo, E., Rescigno, C., Pisapia, R., Plamieri, G., Maraolo, A., Calabria, G., Catalano, M., Fiorentino, G., Annunziata, A., Polistina, G., Imitazione, P., Mollica, M., Esposito, V., D'Abraccio, M., Punzi, R., Bianco, V., Sbreglia, C., Del Vecchio, R. F., Bordonali, A., Franco, A., Salsi, P., Fontana, M., Virzi, G., Calderone, O., Molteni, A., Gennarini, S., Gnudi, U., Ricci, M. A., Titolo, G., Mensi, G., Vuotto, P., Gasperini, B., Mancini, M., Pasquini, Z., Spanu, P., Clementi, S., Pierini, S., Bokor, D., Gori, D., Ciofetti, M., Caimi, M., Bettazzi, L., Allevi, E., Furiani, S., Capitanio, C., Mastropasqua, B., Fara, C., Pulitano, G., Matsuno, J. S., Porta, F. D., Dolfini, V., Beyene, N. B., Bezzi, M., Novali, M., Viale, P., Tedeschi, S., Pascale, R., Bruno, R., Di Filippo, A., Sachs, M., Oggionni, T., Di Stefano, M., Mengoli, C., Facchini, C., De Nardo, D., Frausini, G., Mucci, L., Tedesco, S., Girolimetti, R., Manfredini, E., Di Carlo, A. M., Espinosa, E., Dennetta, D., Ticinesi, A., Meschi, T., Nouvenne, A., Norbiato, C., Vitale, F., Saracco, M., Codeluppi, M., Fronti, E., Ferrante, P., Nespola, G. A., Francisci, D., Tosti, A., Carbonelli, C. M., Greco, A., Tinti, M. G., Stellini, R., Appiani, C., Reghenzi, P., Poletti, V., Ravaglia, C., Tacconi, D., Malcontenti, C., Sainaghi, P. P., Landi, R., Vassia, V., Rizzi, E., Bellan, M., Rossati, A., Castello, L., Mastroianni, C. M., Russo, G., Toffoletto, F., Serino, F. S., Brollo, L., Momesso, E., Turati, M. L., Monforte, A. D., Marchetti, G., Boni, F., Teopompi, E., Trenti, C., Boracchia, L., Minelli, E., Ghidoni, G., Matei, A., Caruso, A., Arcoleo, G., Camarda, G., Catalano, F., Spatafora, M., Bettega, D., Andreoni, M., Teti, E., Sarmati, L., Di Lorenzo, A., Celeste, M., Baratto, F., Monticelli, J., Criveller, P., Antonini, A., Anselmo, Riccio, Castellano, M., Cappelli, C., Corvini, F., Zanini, B., Crippa, M., Ronconi, M., Costa, R., Casella, S., Brentana, L., Bernardi, L., Frascati, A., Panese, S., Presotto, F., Michieletto, L., Bernardi, C., Fusar, M., Agnoletti, V., Farina, M., Russo, Lavorini, F., Ginanni, R., Palmieri, F., Mosti, S., Amaglio, A., Cattaneo, A., Cirri, S., Montisci, A., Gallazzi, C., Cosseta, D., Baronio, B., Rampa, L., Maggi, P., Messina, V., Sabatti, M. C., Palumbo, M., Mazzone, A., Faggioli, P., Bussini, L., Fornaro, G., Volpato, F., Imperiale, D., Manno, E., Ferreri, E., Martelli, D., Verhovez, A., Giorgis, S., Faccio, L., Delli Quadri, R., Negro, C., Converso, M., Bosco, F., Amadosi, S., Prandini, P., Cocchi, S., Manfrin, V., Del Punta, V., Mazzola, G., Sportato, G., Romagnoli, M., Cristini, F., Facondini, F., Perin, T., Boschi, A., Meschiari, M., Guaraldi, G., Modica, S., Moneta, S., Boccalatte, D., Marchetti, V., Amadasi, S., Ebbreo, G., Dale, M., Tura, P., Rizzoni, D., Boari, G. E. M., Bonetti, S., Marini, E., Daniele, I., Grossi, P. A., Delfrate, N. W., Bernhart, O., Spizzo, G., Mahlknecht, K., Volkl, T., Di Pietro, M. A., Trezzi, M., Monacci, C., Peris, A., Bonizzoli, M., Cavanna, L., Moroni, C., Stroppa, E. M., Savio, M. C., Gatti, F., Bartolaminelli, C., Petrosillo, N., Donno, D. R., Taglietti, F., Topino, S., Chinello, P., Galati, V., D'Offizi, G., Taibi, C., Cimolato, B., Moroni, F., Palagano, N., Pelagatti, L., Seravalle, C., Landini, G., Amitrano, M., Raimondo, M., Mangiacapra, S., Romano, A., Atteno, M., Blanc, P., Suardi, L. R., Pallotto, C., Casinelli, K., Uccella, I., Harari, S., Caminati, A., Lipani, F., Di Perri, G., Calcagno, A., Calleri, G., Montrucchio, C., Caputo, A. M., Cozzio, S., Delle Donne, L., Bassetti, M., Malgorzata, M., Nicolini, L. A., Russo, C., Sepulcri, C., Beltramini, S., Mina, F., Puoti, M., Gandino, A., Langer, T., D'Amico, F., Berlendis, M., Rocchetti, C., Cettolo, F., Fausini, G., Bocchi, P., Cioni, G., Cappi, C., Corcione, S., De Rosa, F. G., Scabini, S., Canta, F., Mornese Pinna, S., Pensa, A., Rocco, M., Cirasa, M. T., Spinicci, M., Mencarini, J., Zammarchi, L., Cenderello, G., Sciole, K., Bassi, F., Bianchi, M., Frigerio, S., Spaziani, S., Nucera, A., Rizzardini, G., Cossu, M. V., Antivalle, M., Carpinteri, G., Macheda, S., Labate, D., Bottiroli, M., Erne, E. M., Cristina, Z., Di Biase, V., Malberti, F., Montani, G., Poisa, P., Bettini, D., Cauda, R., Ciccullo, A., Riccardi, N., Angheben, A., Turrini, M., Clerici, R., Gardellini, A., Liparulo, L., Rossini, T., Ucciferri, C., Cipollone, F., Vecchiet, J., Nico, A., Marra, L., Leone, A., Sdanganelli, A., Palmiotti, G. A., D'Alagni, G., Santantonio, T. A., Lo Caputo, S., Bottalico, I., Ponticiello, A., Di Perna, F., Bernardi, E., Beltrame, A., Bravi, S., David, M., Bernardi, P., Galante, D., Uccelli, M. C., Prestini, K., Drera, M., Zini, E., Peregrinelli, A., Blanzuoli, L., Benedetti, V., Calvi, R., Scaglione, N., Nallino, G., Bonazzi, M., Crespi, T., Masolin, T., Regazzetti, A., Cerri, M. C., Maffezzini, E., Piazza, M., Papetti, C., De Filippi, C., Roveda, E., Cipolla, G., Scozzafava, M., Crepaldi, M., Henchi, S., Vanoni, N., Repossi, A., Vezzoli, M., Scorletti, E., Perugini, O., Pasini, S. M., Pacetti, V., Ferrari, L., de Paduanis, G. A., del Duca, S., Dell'Ara, F., Brocchieri, A., Minoja, G., Storti, E., Pitagora, L., Costa, I., Delfanti, F., Orlandi, M., Ruggeri, R., Ruggieri, L., Livigni, S., Silengo, D., Ageno, W., Pedrini, L., Artiol, S., Morbidoni, L., De Donno, G., Ravagnani, V., Inglese, F., Scotton, P. G., Costantini, P., Delucchi, M., Clini, E., Ansuini, A., Baiocchi, M., Lain, G., Vincenzo, B., Rastelli, G., Doria, A., Vianello, A., Cattelan, A. M., Bindoli, S., Felicietti, M., Canetta, C., Scartabellati, A., Accordino, S., Ferrara, M., Cocco, L., Cirillo, F., Pace, E., De Caro, M., Alberico, M., Benigni, G., Damiano, T., Fusco, P., Iuorio, A., Torretta, G., Racagni, M., Muttini, S., Sala, G., Ghiringhelli, P., Chiumiento, F., Baccari, L., Bocchi, F., Benatti, F., Catellani, J., Coppola, M., Papi, A., Bosco, E., Lazzeri, C., Cesira, N., Puttini, C., Carli, T., Croci, L., Corridi, M., Arlotti, M., Guerrini, G., Cola, L., Romanelli, M., Bonifazi, M., Gasparini, S., Mei, F., Cerutti, E., Lacedonia, D., Santoro, A., Guidelli, G. M., Greco, S., Castellan, A., Infantino, G., Camici, L., Covani Frigieri, F. C., Pavoni, V., Migliori, L., Rossetti, B., Montagnini, F., Mauro, I., Genovese, E., Capuozzo, A., Vitiello, L., Sirignano, E., Gnesin, P., Servillo, G., Marinelli, A., Pasero, D., Babudieri, S., Madeddu, G., De Vito, A., Casadio, L., Ranghitta, M., Passalacqua, R., Fioravanti, A., Gentile, I., Buonomo, A. R., Scotto, R., Zappulo, E., Dell'Aquila, G., Bianchetti, A., Guerini, F., Vallone, A., Oppedisano, P., Pusterla, L., Giglio, O., Sartori, E., Zanardini, C., Gatti, P., Valiani, V., Piconi, S., Molteni, C., Dognini, G., Cosimo, F., Guarneri, L., Pulvirenti, F., Mondino, V., Traballi, G., Iemoli, E., Grisolia, A., Giorgi, R., Nucera, G., Raffaelli, V., Marino, P., Negro, E., Serati, L., Tamanini, S., Iacobello, C., Strano, G., Boglione, L., Catania, A., Gipponi, P., Di Cato, L., Panaccione, A., Vitale, G., Crippa, I. A., Giacomini, M., Basile, A., Bellone, A., Tundo, P., Buzzigoli, S., Palmiero, G., Magnaca, A., Silva, M., Ricci, M., Crespi, S., Pasquino, B., Consales, G., Bragantini, D., Mastroianni, F., Righetti, G., Scarafino, A., Bitetto, M., Franzetti, F., Piga, S., Delmonte, V., Carbonara, S., Losappio, R., Dejaco, C., Mastroianni, C., Del Bono, V., Gilioli, F., Barzan, D., De Struppi, S., Carlotto, A., Guadagnin, M. L., Girardis, M., Bertellini, E., Dentali, F., Foresta, G., Baratta, A., Viviani, R., Agrati, A. M., Perego, G. B., Montineri, A., Manuele, R., Bonfante, S., Aquilini, D., Prozzo, A., Santopuoli, D., Di Rosa, Z., Alborghetti, A., Peci, P., Bakhtadze, N., Pandini, C. S., Ashofarir, N., Casella, G., Spagnolli, W., Urru, S., Marchesoni, I., Caminiti, G., Argilloni, E., Danieli, E., Ghirardi, G., Antonioli, C. M., Lipari, A., Zavarise, P., Kokaly, F., Polati, E., Gottin, L., Lucernoni, P., De Conti, F., Marcon, E., Pontali, E., Vacca, E. B., Saffioti, C., Zunino, A., Pognuz, E. R., Berlot, G., Saltori, M., Tedesco, A., Agostini, C., Di Rosolini, M. A., Marino, F., Bellinzona, G., Grassi, W., Di Carlo, M., Scimonello, G., Nonini, S., Mondino, M., Mantovani, L. F., Tenti, E., Tropea, C. M. G., Di Stefano, D. E., Guelfi, P., Dagna, L., Morgana, G., Montemurro, L., Girelli, D., Crisafulli, E., Maroccia, A., Cemuschi, A. M., Bernasconi, M., Zummo, U., Barbato, V., Bevilacqua, S., Buonfanti, G., Canzanella, G., De Matteis, G., Florio, M., Martino, M., Ribecco, M. T., Romano, F., Savio, A., Sparavigna, L., Curvietto, M., Citarella, M., Nava, V., Maggioni, P., Magni, M., Iommelli, C., Bianco, A., Corsini, R., Valli, L., Ruggieri, M. P., Melica, T., Ferrari, A., Cicognini, D., Delliponti, M., Zuccarini, A., Ciani, S., Raffaeli, D., Donati, L., Cannizzo, S., Lui, S., Santini, L., Roncaglia, E., Mighali, P., Eisendle, F., Cerino, G., Citterio, C., Di Nunzio, C., Mancini, A., Lamonica, S., Resimini, S., Sarteschi, G., Pavei, C., Battistini, N., Gazzola, O. E., Miceli, M., Pontiggia, S., Lonati, V., Giannandrea, G., Sortino, C., Ravani, S., Uggeri, C., Jocolle, G., Bare, C., Baroni, I., De Candia, D., Fiorini, B., Chierico, K., Romeo, F., Bottega, R., Boccasile, L., Corsaro, A., Spadoni, C., Chiari, S., Ercolino, G., Dell'Uomo, V., Viri, S., Minato, M., Gazzola, L., Dorina, B., Gianelli, D., Maspero, S., Farinazzo, M., Zanini, P., Sangiovanni, A., Del Giudice, A., Dragonetti, M. M., Bordignon, S., Machiavelli, A. M., Chiodelli, G., Spatarella, M., Zenoni, D., Beretta, F. N., Santilli, G., Badagliacca, R., Angileri, M., Giannelli, L., Campomori, A., Maimone, P., Fadda, A., Faoro, S., Pisterna, A., Cacopardo, B., Marino, A., Pampaloni, A., Celesia, B. M., Cinnella, G., Labella, D., Caporusso, R. R., Danzi, M., Fiscon, M., Malena, M., Fendt, D., Nardi, S., Stobbione, P., Savi, M. L., De Monte, A., Scala, A., Liberato, N. L., Luchi, S., Vincenti, A., Cabrini, L., Pinelli, G., Brugioni, L., Potenza, D., Numis, F. G., Porta, G., D'Amico, M., Iengo, B., Angarano, G., Saracino, A., Blasi, L., De Negri, P., Angelici, S., Farina, A., Martino, G. P., Bitti, G., Tedeschi, A., De Ponti, S., Agostinone, A., Parruti, G., Consorte, A., Frattari, A., Filippelli, A., Pagliano, P., Masullo, A., Sellitto, C., Reta, M., Rossi, N., Raumer, L., Andreassi, S., Brancaleoni, P., Carai, A., Salerno, A. M., Marinangeli, F., Mariani, R., Ciccone, A., Meschini, C., Santoboni, G., Angrisani, C., Micarelli, D., Tarquini, G., Fregoni, V., Volta, C. A., Cherubini, A., Del Prete, M. S., Ciarrochi, E., Tasca, F., Ballarin, A., Bianchin, A., Flocco, R., Cuzzone, V., Carpinteri, M., Gallotti, P., Torre, F., Zannetti, P., Crapis, M., Venturini, S., Barattini, M., Gori, G., Mastroianni, A., De Stefano, G., Gilio, M., Rapisarda, G., Gulisano, L., Granata, M. L., Saglimbene, S., Montalto, M. T., Grasso, I., De Luca, S., Magro, G., Messina, F., Scapino, B., Abrate, P., Francisco, C., Pesce, L., Navarra, M., Agosti, M., Pagani, S., Piluso, M., Ricioppo, A., Tognella, S., Rovere, P., Vincenzi, M., Ghirardi, L., Generali, D., Ingrosso, M., Desiderio, E., Molaro, R., Vitiello, S., Lancione, L., Paone, T. C., Meli, A., Mainardi, S., Rastellino, V., Ursillo, A., di Grigoli, P., Bovetto, E., Stefanetto, I. M., Mazzola, F., Daniele, A., Bisio, C., Delnero, P., Morando, G., Nava, A., Francesco, L., Fiammengo, F., Regis, M., Roccatello, D., Sabato, E., Liccardi, M. M., Bretto, C., Lutri, L., Castenetto, E., Roberti, G., Guidi, M. F., Bini, F., Zappa, M. C., Trequattrini, T., Rivitti, R., Vigliarolo, R., Succu, A., Lilli, M., Serao, M., Giogre, G., Ruggieri, A., Flores, K., Vairo, G., Satira, R., Lingua, A., Spina, R., Nicastri, E., Maffongelli, G., Barreca, F., Scollet, S., Franchi, F., Fabbri, C., Minuz, P., Dalbeni, A., Zanatta, P., Gelormini, D., Mandelli, A., Galderisi, F., Zoia, E., Marchi, M. R., De Almeida Neves, N., Carbone, G., Di Caterino, E., Petrone, A., Usai, C. A., Bandiera, F., Monti, R., Hofer, A., Castiglione, G., Angeletti, C., Tarsia, P., Veronese, L., Artoni, P. D., Larussa, D., Fumagalli, R., Brioschi, P., Cerutti, A., Pasquino, P., Gilberto, F., Cantadori, L., Tomasoni, G., Tomasoni, L. R., Coppola, N., Spolveri, S., Pollastri, C., Fico, L., Principi, T., Pierantozzi, S., Fontana, C., Lubrano, G., Martinelli, L., Navalesi, P., Serra, E., Cogi, E., Manzi, A., Furino, E., Dasseni, N., Gentilini, C., Benatti, E., Pignatti, A., Aiello, G., Milia, M., Covesnon, M. G., Brianti, A., Francesco, C., Ilaria, B., Pagnozzi, F., Mietta, S., Rossi, A., Maroni, L., Borroni, V., Bellintani, C., Sgarabotto, C., Bizzotto, G., Bucci, L., Spagnuolo, G., Agostini, M., Caria, F. C., Testa, F., De Palma, R., Murdaca, G., Zanolini, G., Sala, N., Righini, E., Pontremoli, R., Aondio, G., Riccardi, F., De Cristoforo, M. G., De Michele, F., Storti, A., Perra, R., Deidda, S., Enrica, C., Valastro, F., Pierfranceschi, M. G., De Gennaro, F., Nardecchia, A. L., Castellini, M., Buetto, G., Ippoliti, G., Sicheri, D., Bottoli, M. G., De Arroyabe, B. M. L., Versaci, A., Di Cura Villa Giada Pallotti, C., Civita, M., Grio, M., Liuzzi, N., Molino, P., Pastorelli, M., Ricchiardi, A., Varbella, F., Zeme, A. D., Sighieri, C., Portale, G., Olivetti, A., Pagnoni, C., Moschini, G., Boni, S., Guerra, A., Scudellari, R., Vella, S., Inchiostro, S., Piazza, O., Guarino, S., Aldegheri, G., Napoli, G., Morettini, A., Caldini, E., Menicacci, L., Pieralli, F., Torrini, M., Poggesi, L., Visetti, E. M., Mangano, C., Visconti, S., Maietta, P., Banfi, E., Cartella, S., Venturi, B., Nuceri, A., Chiesa, E., Pacentra, E., Panzolato, G., Giannotti, M., Bianchi, C., Pietrangelo, A., Para, O., Rutili, M. S., Russo, R., Lanfranco, M., Scalabrino, E., Tafuri, A., Perfetti, E., Chiarello, T., Cancanelli, L., Otero, M., Pannella, G., Bellucci, F., Ferrero, G., Vico, C., Stillante, M. S., D'Andrea, G., Amoroso, F., Arcidiacono, A., Bella, A. M., Belsito, A., Berte, Y., Carubia, G., Caruso, M. G., Casella, O., Chiereleson, F., Costa, C., De Franco, D., Germana, G., Messina, A., Musumeci, D., Noto, C., Valenti, M., Sorrentino, C., Panico, R., Schettino, G., Piccoli, J., Pepe, A., De Rosa, F., Ottaviano, M., Marrazzo, G., Raponi, G., Diberardino, S., Bausi, S., Marini, S. F., Giubellino, E., Innocenti, G., Gugliemi, G., Maccari, D., and Baciu, I.
- Subjects
tocilizumab ,covid 19 ,pneumonia - Published
- 2021
6. Main changes in European Clinical Trials Regulation (No 536/2014)
- Author
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Tenti, E., Simonetti, G., Bochicchio, M.T., and Martinelli, G.
- Published
- 2018
- Full Text
- View/download PDF
7. Electronic Capturing of Genetic and Molecular Data in Modern Clinical Trials
- Author
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Ferrari R, Tenti E, Zavan B, Manfrini M, and Balla C
- Subjects
Clinical trial ,medicine.medical_specialty ,business.industry ,medicine ,Medical physics ,business - Published
- 2018
8. S123 SETD2 LOSS OF FUNCTION IS A RECURRENT EVENT IN ADVANCED-PHASE CHRONIC MYELOID LEUKEMIA INDUCED BY POST-TRANSLATIONAL MECHANISMS THAT CAN BE THERAPEUTICALLY TARGETED
- Author
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Mancini, M., primary, De Santis, S., additional, Monaldi, C., additional, Bavaro, L., additional, Martelli, M., additional, Castagnetti, F., additional, Gugliotta, G., additional, Rosti, G., additional, Fontana, M.C., additional, Dan, E., additional, Sinigallia, B., additional, Iurlo, A., additional, Orofino, N., additional, Abbruzzese, E., additional, Salvucci, M., additional, Pregno, P., additional, Gozzini, A., additional, Crugnola, M., additional, Albano, F., additional, Bonifacio, M., additional, Calistri, E., additional, Tiribelli, M., additional, Binotto, G., additional, Imovilli, A., additional, Trabacchi, E., additional, Galimberti, S., additional, Baratè, C., additional, Tenti, E., additional, Baccarani, M., additional, Martinelli, G., additional, Cavo, M., additional, and Soverini, S., additional
- Published
- 2019
- Full Text
- View/download PDF
9. ESTABLISHING A NATIONAL NETWORK OF LABORATORIES USING NEXT GENERATION AMPLICON DEEP SEQUENCING FOR BCR-ABL1 KINASE DOMAIN MUTATION SCREENING: THE 'NEXT-IN-CML' STUDY
- Author
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Soverini, S., Benedittis, C., Bavaro, L., Martelli, M., Stella, S., Iurlo, A., Orofino, N., Barate, C., Galimberti, S., Sica, S., Sora, F., Rossi, A. Russo, Albano, F., Ciceri, F., Lunghi, F., Castagnetti, F., Gugliotta, G., Tenti, E., Rosti, G., CRISTINA PAPAYANNIDIS, Stagno, F., Vigneri, P., Serra, A., Saglio, G., Carnuccio, F., Pane, F., Errichiello, S., Annunziata, M., Breccia, M., Abruzzese, E., Bonifacio, M., Novella, E., Di Bona, E., Sancetta, R., Calistri, E., Spinosa, G., D Adda, M., Capodanno, I., Baccarani, M., Cavo, M., and Martinelli, G.
- Published
- 2017
10. MITRAL VALVE REPLACEMENT OR REPAIR IN INFECTIVE ENDOCARDITIS: ROLE OF THE ISOLATED PATHOGENS ON MORTALITY AND EARLY OR LATE RELAPSE RATE
- Author
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Fiorentino, M, Mikus, E, Costantino, A, Pin, M, Sangiorgi, D, Tenti, E, Tripodi, A, and Savini, C
- Published
- 2024
- Full Text
- View/download PDF
11. INITIAL EXPERIENCE IN TOTAL ENDOSCOPIC MITRAL VALVE SURGERY WITH THREE–DIMENSIONAL VIDEO–ASSISTED TECHNOLOGY
- Author
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Fiorentino, M, Mikus, E, Vostantino, A, Sangiorgi, D, Tenti, E, Tremoli, E, and Savini, C
- Published
- 2024
- Full Text
- View/download PDF
12. ENOS polymorphisms and clinical outcome in advanced HCC patients receiving sorafenib: Final results of the ePHAS Study
- Author
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Casadei Gardini, A., primary, Marisi, G., additional, Faloppi, L., additional, Scarpi, E., additional, Foschi, F.G., additional, Iavarone, M., additional, Lauletta, G., additional, Corbelli, J., additional, Tenti, E., additional, Facchetti, F., additional, della Corte, C., additional, Tamberi, S., additional, Cascinu, S., additional, Scartozzi, M., additional, Amadori, D., additional, Nanni, O., additional, Ulivi, P., additional, and Frassineti, G.L., additional
- Published
- 2016
- Full Text
- View/download PDF
13. eNOS polymorphisms in relation to outcome in advanced HCC patients receiving sorafenib. Final results of ePHAS study
- Author
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Casadei Gardini, A., primary, Marisi, G., additional, Scartozzi, M., additional, Faloppi, L., additional, Foschi, F., additional, Corbelli, J., additional, Scarpi, E., additional, Iavarone, M., additional, Lauletta, G., additional, Ulivi, P., additional, Tamberi, S., additional, Nanni, O., additional, Cascinu, S., additional, Tenti, E., additional, and Frassineti, G.L., additional
- Published
- 2015
- Full Text
- View/download PDF
14. eNOS polymorphisms in relation to outcome in advanced HCC patients receiving sorafenib
- Author
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Gardini, A. Casadei, primary, Marisi, G., additional, Scarpi, E., additional, Scartozzi, M., additional, Foschi, F.G., additional, Faloppi, L., additional, Tenti, E., additional, Tamberi, S., additional, Tamburini, E., additional, Frassineti, G.L., additional, Cascinu, S., additional, and Ulivi, P., additional
- Published
- 2015
- Full Text
- View/download PDF
15. OHP-011 Pharmacovigilance in the conduct of clinical trials: the experience of an Italian ethics committee
- Author
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Burioli, P, primary, Benini, G, additional, Tenti, E, additional, and Minguzzi, M, additional
- Published
- 2014
- Full Text
- View/download PDF
16. Use of non-conventional medicines by cancer patients,Uso di medicinali non convenzionali da parte di pazienti con tumore
- Author
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Tenti, E., Casadei Gardini, A., ORIANA NANNI, Foca, F., and Cumero, S.
17. THE ADDITION OF GEMTUZUMAB OZAGAMICIN (GO) TO INTENSIVE CHEMOTHERAPY SIGNIFICANTLY IMPROVES COMPLETE RESPONSES CR RATES AND OVERALL SURVIVAL IN PATIENTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA
- Author
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Sartor, C., Papayannidis, C., anna candoni, Malagola, M., Marconi, G., Tenti, E., Manfrini, M., Simonetti, G., Zuffa, E., Abbenante, M. C., Parisi, S., Paolini, S., Lo Monaco, S., Franchini, E., Ottaviani, E., Fontana, M. C., Padella, A., Guadagnuolo, V., Fanin, R., Russo, D., and Martinelli, G.
18. Prospective assessment of NGS-detectable mutations in CML patients with nonoptimal response: The NEXT-in-CML study
- Author
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Anna Serra, Antonio Percesepe, Gabriele Gugliotta, Caterina Musolino, Gianni Binotto, Elisabetta Abruzzese, Immacolata Attolico, Gianantonio Rosti, Mario Annunziata, Rosaria Sancetta, Mariella Girasoli, Fabrizio Pane, Maria Antonella Laginestra, Sara Galimberti, Alessandra Iurlo, Stefania Stella, Sabrina Coluzzi, Simona Sica, Monica Bocchia, Marzia Salvucci, Francesca Lunghi, Fabio Stagno, Nicola Orofino, Stefano Pileri, Federica Sorà, Santa Errichiello, Elisabetta Calistri, Paolo Vigneri, Fausto Castagnetti, Michele Baccarani, Luana Bavaro, Michele Cavo, Eros Di Bona, Francesco Di Raimondo, Claudia Baratè, Margherita Martelli, Simona Soverini, Antonella Russo Rossi, Francesco Albano, Mariella D'Adda, Fabio Ciceri, Flavio Mignone, Elena Tenti, Caterina De Benedittis, Giuseppe Saglio, Isabella Capodanno, Giovanni Martinelli, Massimiliano Bonifacio, Luigi Scaffidi, Soverini, S., Bavaro, L., de Benedittis, C., Martelli, M., Iurlo, A., Orofino, N., Sica, S., Sora, F., Lunghi, F., Ciceri, F., Galimberti, S., Barate, C., Bonifacio, M., Scaffidi, L., Castagnetti, F., Gugliotta, G., Albano, F., Rossi, A. V. R., Stagno, F., di Raimondo, F., D'Adda, M., di Bona, E., Abruzzese, E., Binotto, G., Sancetta, R., Salvucci, M., Capodanno, I., Girasoli, M., Coluzzi, S., Attolico, I., Musolino, C., Calistri, E., Annunziata, M., Bocchia, M., Stella, S., Serra, A., Errichiello, S., Saglio, G., Pane, F., Vigneri, P., Mignone, F., Laginestra, M. A., Pileri, S. A., Percesepe, A., Tenti, E., Rosti, G., Baccarani, M., Cavo, M., Martinelli, G., Soverini, Simona, Bavaro, Luana, De Benedittis, Caterina, Martelli, Margherita, Iurlo, Alessandra, Orofino, Nicola, Sica, Simona, Sora, Federica, Lunghi, Francesca, Ciceri, Fabio, Galimberti, Sara, Baratè, Claudia, Bonifacio, Massimiliano, Scaffidi, Luigi, Castagnetti, Fausto, Gugliotta, Gabriele, Albano, Francesco, Russo Rossi, Antonella Vita, Stagno, Fabio, Di Raimondo, Francesco, D'Adda, Mariella, Di Bona, Ero, Abruzzese, Elisabetta, Binotto, Gianni, Sancetta, Rosaria, Salvucci, Marzia, Capodanno, Isabella, Girasoli, Mariella, Coluzzi, Sabrina, Attolico, Immacolata, Musolino, Caterina, Calistri, Elisabetta, Annunziata, Mario, Bocchia, Monica, Stella, Stefania, Serra, Anna, Errichiello, Santa, Saglio, Giuseppe, Pane, Fabrizio, Vigneri, Paolo G, Mignone, Flavio, Laginestra, Maria Antonella, Pileri, Stefano A, Percesepe, Antonio, Tenti, Elena, Rosti, Gianantonio, Baccarani, Michele, Cavo, Michele, and Martinelli, Giovanni
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Oncology ,Male ,Mutation rate ,bcr-abl ,Drug Resistance ,Fusion Proteins, bcr-abl ,Gene mutation ,medicine.disease_cause ,Settore MED/01 - STATISTICA MEDICA ,Biochemistry ,Adult ,Aged ,Aged, 80 and over ,Drug Resistance, Neoplasm ,Female ,High-Throughput Nucleotide Sequencing ,Humans ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Middle Aged ,Mutation ,Mutation Rate ,Prospective Studies ,Protein Kinase Inhibitors ,hemic and lymphatic diseases ,80 and over ,cml mutation ,BCR-ABL mutations ,Chronic ,Prospective cohort study ,Sanger sequencing ,Leukemia ,Chronic myeloid leukemia ,Myeloid leukemia ,Hematology ,TKI ,NGS ,symbols ,Human ,medicine.medical_specialty ,Immunology ,symbols.namesake ,CML, TKIs, BCR-ABL1 ,Chronic myeloid leukemia,TKI,BCR-ABL mutations,Sanger Sequencing,NGS ,Internal medicine ,medicine ,business.industry ,Fusion Proteins ,Cell Biology ,medicine.disease ,Clinical trial ,Prospective Studie ,Sanger Sequencing ,Neoplasm ,BCR-ABL Positive ,business ,Myelogenous - Abstract
In chronic myeloid leukemia (CML) patients, tyrosine kinase inhibitors (TKIs) may select for drug-resistant BCR-ABL1 kinase domain (KD) mutants. Although Sanger sequencing (SS) is considered the gold standard for BCR-ABL1 KD mutation screening, next-generation sequencing (NGS) has recently been assessed in retrospective studies. We conducted a prospective, multicenter study (NEXT-in-CML) to assess the frequency and clinical relevance of low-level mutations and the feasibility, cost, and turnaround times of NGS-based BCR-ABL1 mutation screening in a routine setting. A series of 236 consecutive CML patients with failure (n = 124) or warning (n = 112) response to TKI therapy were analyzed in parallel by SS and NGS in 1 of 4 reference laboratories. Fifty-one patients (22 failure, 29 warning) who were negative for mutations by SS had low-level mutations detectable by NGS. Moreover, 29 (27 failure, 2 warning) of 60 patients who were positive for mutations by SS showed additional low-level mutations. Thus, mutations undetectable by SS were identified in 80 out of 236 patients (34%), of whom 42 (18% of the total) had low-level mutations somehow relevant for clinical decision making. Prospective monitoring of mutation kinetics demonstrated that TKI-resistant low-level mutations are invariably selected if the patients are not switched to another TKI or if they are switched to a inappropriate TKI or TKI dose. The NEXT-in-CML study provides for the first time robust demonstration of the clinical relevance of low-level mutations, supporting the incorporation of NGS-based BCR-ABL1 KD mutation screening results in the clinical decision algorithms.
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- 2020
19. Clinical experience with dalbavancin for the treatment of deep sternal wound infection
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Maddalena Giannella, Elena Tenti, Sara K. Tedeschi, Fabio Tumietto, Pierluigi Viale, Simone Calvi, Renato Pascale, Michele Bartoletti, Elisa Mikus, Bartoletti M., Mikus E., Pascale R., Giannella M., Tedeschi S., Calvi S., Tenti E., Tumietto F., and Viale P.
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0301 basic medicine ,Microbiology (medical) ,Male ,Methicillin-Resistant Staphylococcus aureus ,medicine.medical_specialty ,Sternum ,Lipoglycopeptide ,medicine.drug_class ,Deep sternal wound infection ,030106 microbiology ,Immunology ,Antibiotics ,Microbiology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Postoperative Complications ,Interquartile range ,Immunology and Allergy ,Medicine ,Humans ,Surgical Wound Infection ,030212 general & internal medicine ,Aged ,Retrospective Studies ,business.industry ,Cardiovascular Surgical Procedures ,Dalbavancin ,Middle Aged ,Staphylococcal Infections ,Cardiac surgery ,medicine.disease ,Mediastinitis ,Surgery ,Anti-Bacterial Agents ,chemistry ,Female ,Teicoplanin ,business ,Complication ,Cohort study - Abstract
Objectives Deep sternal wound infection (DSWI) is a complication of major heart surgery with high morbidity as well as prolonged antimicrobial treatment and hospital length of stay (LoS). Dalbavancin is a new lipoglycopeptide antibiotic active against Gram-positive micro-organisms, including methicillin-resistant Staphylococcus aureus (MRSA), with a long half-life. This small case series assessed the feasibility of dalbavancin for the treatment of DSWI. Methods This was retrospective, observational, cohort study of patients treated with dalbavancin for DSWI over a 2-year period (March 2016 to April 2018) in two cardiac surgery departments in Italy. All patients with DSWI underwent surgical accurate debridement. Dalbavancin was administered during the hospital stay or in an outpatient facility. Results Among 15 patients enrolled in the study, MRSA was isolated in 7 (47%), methicillin-resistant Staphylococcus epidermidis in 6 (40%) and other coagulase-negative staphylococci in 2 (13%). Dalbavancin was administered by two infusions in 9 patients (60%), whereas 5 patients (33%) received a median of four doses. Fourteen patients received a first dose of 1000 mg followed by 500 mg, whereas one patient received two doses of 1500 mg each. All patients were defined as clinically cured. The median hospital LoS was 13 days (interquartile range, 8–18 days). At 6 months after discharge, 14 patients (93%) showed no relapse of DSWI, whereas 1 patient recurred with a diagnosis of DSWI caused by another pathogen (Candida sp.). Conclusion Dalbavancin may be an alternative option for DSWI caused by Gram-positive bacteria when first-line treatments are contraindicated or as salvage treatment.
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- 2019
20. Aneuploidy: Cancer strength or vulnerability?
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Simonetti, Giorgia, Bruno, Samantha, Padella, Antonella, Tenti, Elena, Martinelli, Giovanni, Simonetti G., Bruno S., Padella A., Tenti E., and Martinelli G.
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Spindle Apparatu ,Models, Genetic ,Carcinogenesis ,Animal ,Mini Review ,Spindle Apparatus ,M Phase Cell Cycle Checkpoint ,Aneuploidy ,spindle assembly checkpoint ,Gene Expression Regulation, Neoplastic ,Neoplasms ,Chromosomal Instability ,Animals ,Humans ,M Phase Cell Cycle Checkpoints ,cancer therapy ,Neoplasm ,carcinogenesi ,Human - Abstract
Aneuploidy is a very rare and tissue-specific event in normal conditions, occurring in a low number of brain and liver cells. Its frequency increases in age-related disorders and is one of the hallmarks of cancer. Aneuploidy has been associated with defects in the spindle assembly checkpoint (SAC). However, the relationship between chromosome number alterations, SAC genes and tumor susceptibility remains unclear. Here, we provide a comprehensive review of SAC gene alterations at genomic and transcriptional level across human cancers and discuss the oncogenic and tumor suppressor functions of aneuploidy. SAC genes are rarely mutated but frequently overexpressed, with a negative prognostic impact on different tumor types. Both increased and decreased SAC gene expression show oncogenic potential in mice. SAC gene upregulation may drive aneuploidization and tumorigenesis through mitotic delay, coupled with additional oncogenic functions outside mitosis. The genomic background and environmental conditions influence the fate of aneuploid cells. Aneuploidy reduces cellular fitness. It induces growth and contact inhibition, mitotic and proteotoxic stress, cell senescence and production of reactive oxygen species. However, aneuploidy confers an evolutionary flexibility by favoring genome and chromosome instability (CIN), cellular adaptation, stem cell-like properties and immune escape. These properties represent the driving force of aneuploid cancers, especially under conditions of stress and pharmacological pressure, and are currently under investigation as potential therapeutic targets. Indeed, promising results have been obtained from synthetic lethal combinations exploiting CIN, mitotic defects, and aneuploidy-tolerating mechanisms as cancer vulnerability.
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- 2019
21. The Role of Microbes in Surgical Decision Making for Infective Endocarditis: Mitral Valve Repair or Replacement?
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Mikus E, Fiorentino M, Sangiorgi D, Pascale R, Costantino A, Nocera C, Calvi S, Tenti E, Tremoli E, Tripodi A, and Savini C
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Background: The benefits of mitral repair versus replacement for endocarditis are inconclusive. This study compares outcomes of patients with infective endocarditis undergoing mitral valve repair versus replacement and investigates the impact of microbial etiology., Methods: All 251 patients undergoing mitral valve surgery for active endocarditis between 2010 and 2023 were enrolled, 180 (71.7%) replacement and 71 (28.3%) repair. To adjust for imbalances, inverse probability of treatment weighting was applied and 187 patients were obtained., Results: The analysis between groups, following the application of inverse probability of treatment weighting, showed no statistically significant differences across all considered outcomes. Early and late death was observed respectively in 6 (8.5%) and 11 (15.5%) patients in the repair group versus 24 (13.3%) and 45 (25.0%) in the replacement group without statistical significance ( p = 0.221 and p = 0.446). Relapse occurred in six patients (8.5%) in the repair group after a median time of 4.0 months and in six (3.3%) in the replacement after 6.9 months ( p = 0.071)., Conclusions: Surgical strategy in mitral endocarditis has no effect on major postoperative complications, mortality, or medium/long-term survival. Staphylococcus aureus and Coagulase-negative Staphylococci represent a risk for early mortality and relapse. However, mitral valve repair for endocarditis can be pursued when it ensures the complete eradication of all infected tissue, particularly in cases caused by Streptococcus infection, in young patients, and after a minimum of 18 days of antibiotic therapy.
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- 2024
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22. Surgical Treatment of Active Endocarditis Pre- and Post-COVID-19 Pandemic Onset.
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Mikus E, Fiorentino M, Sangiorgi D, Fiaschini C, Tenti E, Tremoli E, Calvi S, Costantino A, Tripodi A, Zucchetta F, and Savini C
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Background: Despite advanced diagnosis and treatment, infective endocarditis (IE) is a potentially life-threatening condition. The impact of COVID-19 on the diagnosis and outcome of the surgical treatment of IE is uncertain. The aim of this study was to analyze the incidence, characteristics, and outcomes of surgically treated IE before and after the COVID-19 pandemic., Methods: This study retrospectively analyzed the data of 535 patients who underwent valve surgical procedures for IE between January 2010 and December 2022 in a single cardiac surgery center. Patients were divided into two groups depending on the date of their operation: before ( n = 393) and after ( n = 142) COVID-19 onset. In order to balance the groups, inverse probability of treatment weighting (IPTW) calculated from the propensity score (PS) was applied. Weighted univariate logistic regressions were reported for outcomes; weights were derived from IPTW. Interrupted time series analysis (ITSA) according to Linden's method was used to evaluate the changes in the manifestation of IE after 11 March 2020., Results: Patients from the post-COVID-19 cohort (after 11 March 2020) had a greater number of comorbidities such as diabetes (29.6% vs. 16.3% p = 0.001), hypertension (71.1% vs. 59.5% p = 0.015), and preoperative kidney injury requiring dialysis (9.2% vs. 2.5% p = 0.002), but the median additive and logistic EuroSCORE were not statistically different. In the post-COVID-19 group, we observed a greater prevalence of Staphylococcus aureus -related endocarditis (24.5% vs. 15.4% p = 0.026), a consequent reduction in Staphylococcus non aureus -related endocarditis (12.2% vs. 20.1% p = 0.048), and a decrease in aortic valve replacements (43.0% vs. 53.9%), while the number of mitral valve replacements and repair was greater (21.1% vs. 15.0% and 6.3% vs. 4.3%, respectively). No differences were found in the two groups concerning early death, death, or relapse at 1 year after surgery. Data obtained by multivariable analysis identified preoperative renal dysfunction requiring dialysis as the only common risk factor for early mortality via stratifying by time periods in analysis., Conclusions: The incidence of surgically treated IE significantly increases after the COVID-19 pandemic with a higher incidence of mitral valve involvement with respect to the aortic valve. Although a delay in surgical timing occurred during the COVID-19 pandemic, data in terms of mortality and outcomes were largely unaffected.
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- 2024
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23. Post-Operative Delirium and Cognitive Dysfunction in Aged Patients Undergoing Cardiac Surgery: A Randomized Comparison between Two Blood Oxygenators.
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Mantovani L, Mikus E, Tenti E, Sangiorgi D, Zannoni S, Cavallucci A, Ferroni L, Cimaglia P, Tolio V, Tremoli E, and Savini C
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In elderly patients undergoing cardiac surgery, extracorporeal circulation affects the incidence of post-operative delirium and cognitive impairment with an impact on quality of life and mortality. In this study, a new oxygenator system (RemoweLL 2) was tested against a conventional system to assess its efficacy in reducing the onset of postoperative delirium and cognitive dysfunction and the levels of serum inflammatory markers. A total of 154 patients (>65 y.o.) undergoing cardiopulmonary bypass (CPB) were enrolled and randomly assigned to oxygenator RemoweLL 2 ( n = 81) or to gold standard device Inspire ( n = 73) between September 2019 and March 2022. The aims of the study were to assess the incidence of delirium and the cognitive decline by neuropsychiatric tests and the MoCa test intra-hospital and at 6 months after CPB. Inflammation biomarkers in both groups were also evaluated. Before the CPB, the experimental groups were comparable for all variables. After CPB, the incidence of severe post-operative delirium showed a better trend ( p = 0.093) in patients assigned to RemoweLL 2 (16.0%) versus Inspire (26.0%). Differences in enolase levels ( p = 0.049), white blood cells ( p = 0.006), and neutrophils ( p = 0.003) in favor of RemoweLL 2 were also found. The use of novel and better construction technologies in CPB oxygenator devices results in measurable better neurocognitive and neurological outcomes in the elderly population undergoing CPB.
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- 2023
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24. Albumin Thiolation and Oxidative Stress Status in Patients with Aortic Valve Stenosis.
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Savini C, Tenti E, Mikus E, Eligini S, Munno M, Gaspardo A, Gianazza E, Greco A, Ghilardi S, Aldini G, Tremoli E, and Banfi C
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- Humans, Serum Albumin, Oxidative Stress, Acetylcysteine pharmacology, Sulfhydryl Compounds, Antioxidants, Aortic Valve Stenosis
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Recent evidence indicates that reactive oxygen species play an important causative role in the onset and progression of valvular diseases. Here, we analyzed the oxidative modifications of albumin (HSA) occurring on Cysteine 34 and the antioxidant capacity of the serum in 44 patients with severe aortic stenosis (36 patients underwent aortic valve replacement and 8 underwent a second aortic valve substitution due to a degenerated bioprosthetic valve), and in 10 healthy donors (controls). Before surgical intervention, patients showed an increase in the oxidized form of albumin (HSA-Cys), a decrease in the native reduced form (HSA-SH), and a significant reduction in serum free sulfhydryl groups and in the total serum antioxidant activity. Patients undergoing a second valve replacement showed levels of HSA-Cys, free sulfhydryl groups, and total antioxidant activity similar to those of controls. In vitro incubation of whole blood with aspirin (ASA) significantly increased the free sulfhydryl groups, suggesting that the in vivo treatment with ASA may contribute to reducing oxidative stress. We also found that N-acetylcysteine and its amide derivative were able to regenerate HSA-SH. In conclusion, the systemic oxidative stress reflected by high levels of HSA-Cys is increased in patients with aortic valve stenosis. Thiol-disulfide breaking agents regenerate HSA-SH, thus paving the way to the use these compounds to mitigate the oxidative stress occurring in the disease.
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- 2023
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25. Less Is More? Combined Approaches to Improve Mortality and Morbidity after Aortic Valve Replacement.
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Mikus E, Fiorentino M, Sangiorgi D, Calvi S, Tenti E, Cavallucci A, Tremoli E, Tripodi A, Pin M, and Savini C
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Background: Nowadays, one of the main goals of aortic valve surgery is to reduce the biological impact, mortality, and complications. It is well-known that long operative times in terms of the extracorporeal circulation, but above all, of the aortic cross-clamp time (ACC), represent a risk factor for mortality in patients undergoing cardiac surgery. In order to shorten the aortic cross-clamp time, many technological improvements, such as sutureless prostheses, have been introduced, but their actual effectiveness has not been proven yet. The aim of this study was to assess the 30-day outcomes of patients undergoing aortic valve replacement surgery, focusing on the ACC length., Methods: All 3139 patients undergoing aortic valve replacement between January 2013 and July 2022 at our institution were enrolled. The data were retrospectively collected and the baseline characteristics and intraoperative variables were recorded. In order to adjust the results according to the differences in the baseline characteristics, propensity score matching was performed and four groups of 351 patients were obtained based on the first, second, third, and fourth quartile of the ACC time., Results: The patient population included 132 redo surgeries (9.4%) and 61 cases of active endocarditis (4.3%), with an overall median EuroSCORE II of 1.8 (IQR 1.2-3.1). An increase across the groups was observed in terms of the acute kidney failure ( p < 0.001) incidence, the number of blood transfusions ( p = 0.022), prolonged hospital stays ( p < 0.001), the and respiratory failure ( p < 0.001) incidence. A p of < 0.1 was found for the 30-day mortality ( p = 0.079). The predictors of an early 30-day mortality were standard full sternotomy (OR 2.48, 95% CI 1.14-5.40, p = 0.022), EuroSCORE II (OR 1.10, 95% CI 1.05-1.16, p < 0.001), and a trend for a longer ACC time (Q4 vs. Q1: OR 2.62, 95% CI 0.89-7.68, p = 0.080)., Conclusions: Shortening the operative times resulted in marked improvements of the patients' outcomes. The combined use of minimally invasive approaches and sutureless aortic valve prostheses allows for a lower 30-day events rate. New technologies should be assessed to obtain the best results with the least risk.
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- 2023
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26. A retrospective multicentre study on dalbavancin effectiveness and cost-evaluation in sternotomic wound infection treatment: DALBA SWIT Study.
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Pascale R, Maccaro A, Mikus E, Baldassarre M, Tazza B, Esposito F, Rinaldi M, Tenti E, Ambretti S, Albertini A, Viale P, Giannella M, and Bartoletti M
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- Aged, Cost-Benefit Analysis, Daptomycin therapeutic use, Female, Humans, Male, Middle Aged, Retrospective Studies, Anti-Bacterial Agents economics, Anti-Bacterial Agents therapeutic use, Methicillin-Resistant Staphylococcus aureus, Staphylococcal Infections drug therapy, Teicoplanin analogs & derivatives, Teicoplanin therapeutic use, Wound Infection drug therapy
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Objective: To evaluate the cost-effectiveness of dalbavancin compared with standard of care (SoC) treatment as daptomycin or teicoplanin in patients with sternal wound infections (SWI)., Methods: Multicentre retrospective study of patients diagnosed with SWI from January 2016 to December 2019 at two cardiac surgery facilities treated with dalbavancin, teicoplanin or daptomycin. Patients with SWI treated with dalbavancin were compared with SoC to evaluate resolution of infection at 90 and 180 days from infection diagnosis, length of stay (LoS) and management costs., Results: 48 patients with SWI were enrolled, 25 (50%) male, median age 67 (60-73) years, Charlson index score 5 (4-7). Fifteen patients were treated with dalbavancin (31%) and 33 with SoC (69%): teicoplanin in 21 (63%), and daptomycin in 12 (37%). Staphylococcus species were the most frequent isolates (44, 92%), mostly (84%) resistant to methicillin. All patients were treated with surgical debridement followed by negative pressure wound therapy. Wound healing at day 90 and 180 was achieved in 46 (95.8%) and 34 (82.9%) of patients, respectively. A shorter length of hospitalization in patients treated with dalbavancin compared with SoC [12 (7-18) days vs 22 (12-36) days, p:0.009] was found. Treatment with dalbavancin resulted in total cost savings of €16 026 (95% CI 5976-26 076, P < 0.001). Savings were mainly related to the LoS that was significantly shorter in the dalbavancin group, generating significantly lower cost compared to SoC group., Conclusion: Dalbavancin treatment of sternal wound infections is effective and seems to reduce hospitalization length, leading to significantly lower costs., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2022
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27. High-Sensitivity Cardiac Troponin Predicts Major Cardiovascular Events in Diabetic Patients With Critical Limb Ischemia and Foot Lesions.
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Cimaglia P, Dalla Paola L, Carone A, Scavone G, Manfrini M, Brogneri S, Tenti E, Pavasini R, Bernucci D, Passarini G, Vitali F, Gaudenzi E, Ferrari R, and Campo G
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Background: Diabetic patients with critical limb ischemia (CLI) and foot lesions show a poor prognosis. Optimal risk stratification to guide tailored intervention is still uncertain. The aim of the present study was to assess the prognostic role of high-sensitivity cardiac troponin T (hs-TnT) in such a high-risk population. Methods and Results: Clinical, laboratory, and interventional data, as well as the SPINACH score, were collected. Hs-TnT was measured at hospital admission. All patients were followed up for at least 1 year. The primary endpoint was the cumulative occurrence of major cardiovascular events (MACEs, all-cause death, myocardial infarction, or stroke). The secondary endpoint was all-cause mortality. Overall, 618 patients were included and followed for a median of 981 (557-1,325) days. Diagnosis of coronary artery disease (CAD) was established in 270 (43.7%) patients. Median hs-TnT at admission was 31 (20-59) ng/L, with 525 (85%) patients over the upper reference limit. Hs-TnT values were significantly higher in patients with established CAD (39 vs. 29 ng/L, p < 0.01). Hs-TnT was an independent predictor of MACE (HR 2.440, 95% CI 1.706-3.489, p < 0.001). The best cut-offs were 40 ng/L (AUC 0.711) for patients with established CAD and 25 ng/L (AUC 0.725) for those without. Hs-TnT emerged also as an independent predictor of all-cause mortality. The addition of hs-TnT improved prognostic value of the SPINACH score. Conclusions: Hs-TnT is a powerful biomarker for prognostic stratification of diabetic CLI patients with foot lesions. This is confirmed independently to CAD diagnosis and permits the identification of higher risk patients requiring tailored intervention., 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 © 2021 Cimaglia, Dalla Paola, Carone, Scavone, Manfrini, Brogneri, Tenti, Pavasini, Bernucci, Passarini, Vitali, Gaudenzi, Ferrari and Campo.)
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- 2021
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28. Pacemaker need after sutureless aortic valve replacement: the role of the learning curve.
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Mikus E, Calvi S, Tavazzi L, Brega C, Tripodi A, Pin M, Manfrini M, Zucchetta F, Tenti E, and Albertini A
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- Aged, Aged, 80 and over, Aortic Valve surgery, Aortic Valve Stenosis complications, Arrhythmias, Cardiac etiology, Female, Humans, Male, Postoperative Complications etiology, Prosthesis Design, Retrospective Studies, Treatment Outcome, Aortic Valve Stenosis surgery, Arrhythmias, Cardiac prevention & control, Heart Valve Prosthesis Implantation methods, Learning Curve, Pacemaker, Artificial, Postoperative Complications prevention & control, Sutureless Surgical Procedures methods
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Aim: Aortic valve replacement (AVR) using sutureless prosthesis is a reasonable alternative in those patients with aortic stenosis who would benefit from reduced cross clamp time, such as elderly and high-risk patients. Actually, excellent performances have been demonstrated in hemodynamic outcomes and safety, but some questions remain open regarding long-term durability and the need for postoperative pacemaker implantation., Methods: Between January 2014 and August 2019, all 436 patients [male 40.6%, median age 78 years interquartile range (73-82)] treated with sutureless AVR with a Perceval prosthesis were included in our analysis., Results: The univariate logistic regression showed previous aortic valve surgery [P = 0.028; odds ratio (OR) 3.248], dialysis (P = 0.036; OR 6.435), renal insufficiency (P = 0.021; OR 2.75), EuroSCORE II (P = 0.016; OR 1.051) and year of operation (P < 0.01; OR 0.658) as factors associated with the development of atrioventricular type II or type III block or junctional block requiring pacemaker implantation. The overall incidence of pacemaker implantation after sutureless AVR was 7.1% in the current study, but it dropped to 3.8 and 4.7%, respectively, in 2018 and 2019., Conclusion: The Perceval aortic valve is associated with encouraging postoperative results. The incidence of pacemaker implantation is strictly linked to the surgeons' experience, decreasing year by year after an adequate sizing, reaching a percentage comparable with sutured valve., (Copyright © 2020 Italian Federation of Cardiology - I.F.C. All rights reserved.)
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- 2021
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29. Prospective assessment of NGS-detectable mutations in CML patients with nonoptimal response: the NEXT-in-CML study.
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Soverini S, Bavaro L, De Benedittis C, Martelli M, Iurlo A, Orofino N, Sica S, Sorà F, Lunghi F, Ciceri F, Galimberti S, Baratè C, Bonifacio M, Scaffidi L, Castagnetti F, Gugliotta G, Albano F, Russo Rossi AV, Stagno F, di Raimondo F, D'Adda M, di Bona E, Abruzzese E, Binotto G, Sancetta R, Salvucci M, Capodanno I, Girasoli M, Coluzzi S, Attolico I, Musolino C, Calistri E, Annunziata M, Bocchia M, Stella S, Serra A, Errichiello S, Saglio G, Pane F, Vigneri P, Mignone F, Laginestra MA, Pileri SA, Percesepe A, Tenti E, Rosti G, Baccarani M, Cavo M, and Martinelli G
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- Adult, Aged, Aged, 80 and over, Drug Resistance, Neoplasm, Female, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged, Mutation, Mutation Rate, Prospective Studies, Fusion Proteins, bcr-abl genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Protein Kinase Inhibitors therapeutic use
- Abstract
In chronic myeloid leukemia (CML) patients, tyrosine kinase inhibitors (TKIs) may select for drug-resistant BCR-ABL1 kinase domain (KD) mutants. Although Sanger sequencing (SS) is considered the gold standard for BCR-ABL1 KD mutation screening, next-generation sequencing (NGS) has recently been assessed in retrospective studies. We conducted a prospective, multicenter study (NEXT-in-CML) to assess the frequency and clinical relevance of low-level mutations and the feasibility, cost, and turnaround times of NGS-based BCR-ABL1 mutation screening in a routine setting. A series of 236 consecutive CML patients with failure (n = 124) or warning (n = 112) response to TKI therapy were analyzed in parallel by SS and NGS in 1 of 4 reference laboratories. Fifty-one patients (22 failure, 29 warning) who were negative for mutations by SS had low-level mutations detectable by NGS. Moreover, 29 (27 failure, 2 warning) of 60 patients who were positive for mutations by SS showed additional low-level mutations. Thus, mutations undetectable by SS were identified in 80 out of 236 patients (34%), of whom 42 (18% of the total) had low-level mutations somehow relevant for clinical decision making. Prospective monitoring of mutation kinetics demonstrated that TKI-resistant low-level mutations are invariably selected if the patients are not switched to another TKI or if they are switched to a inappropriate TKI or TKI dose. The NEXT-in-CML study provides for the first time robust demonstration of the clinical relevance of low-level mutations, supporting the incorporation of NGS-based BCR-ABL1 KD mutation screening results in the clinical decision algorithms., (© 2020 by The American Society of Hematology.)
- Published
- 2020
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30. Clinical experience with dalbavancin for the treatment of deep sternal wound infection.
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Bartoletti M, Mikus E, Pascale R, Giannella M, Tedeschi S, Calvi S, Tenti E, Tumietto F, and Viale P
- Subjects
- Aged, Anti-Bacterial Agents therapeutic use, Cardiovascular Surgical Procedures adverse effects, Female, Humans, Male, Mediastinitis microbiology, Methicillin-Resistant Staphylococcus aureus drug effects, Methicillin-Resistant Staphylococcus aureus isolation & purification, Middle Aged, Postoperative Complications, Retrospective Studies, Staphylococcal Infections epidemiology, Staphylococcal Infections microbiology, Sternum surgery, Surgical Wound Infection epidemiology, Teicoplanin administration & dosage, Teicoplanin analogs & derivatives, Mediastinitis drug therapy, Staphylococcal Infections drug therapy, Sternum microbiology, Surgical Wound Infection drug therapy, Teicoplanin therapeutic use
- Abstract
Objectives: Deep sternal wound infection (DSWI) is a complication of major heart surgery with high morbidity as well as prolonged antimicrobial treatment and hospital length of stay (LoS). Dalbavancin is a new lipoglycopeptide antibiotic active against Gram-positive micro-organisms, including methicillin-resistant Staphylococcus aureus (MRSA), with a long half-life. This small case series assessed the feasibility of dalbavancin for the treatment of DSWI., Methods: This was retrospective, observational, cohort study of patients treated with dalbavancin for DSWI over a 2-year period (March 2016 to April 2018) in two cardiac surgery departments in Italy. All patients with DSWI underwent surgical accurate debridement. Dalbavancin was administered during the hospital stay or in an outpatient facility., Results: Among 15 patients enrolled in the study, MRSA was isolated in 7 (47%), methicillin-resistant Staphylococcus epidermidis in 6 (40%) and other coagulase-negative staphylococci in 2 (13%). Dalbavancin was administered by two infusions in 9 patients (60%), whereas 5 patients (33%) received a median of four doses. Fourteen patients received a first dose of 1000mg followed by 500mg, whereas one patient received two doses of 1500mg each. All patients were defined as clinically cured. The median hospital LoS was 13 days (interquartile range, 8-18 days). At 6 months after discharge, 14 patients (93%) showed no relapse of DSWI, whereas 1 patient recurred with a diagnosis of DSWI caused by another pathogen (Candida sp.)., Conclusion: Dalbavancin may be an alternative option for DSWI caused by Gram-positive bacteria when first-line treatments are contraindicated or as salvage treatment., (Copyright © 2019 International Society for Antimicrobial Chemotherapy. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2019
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31. Aneuploidy: Cancer strength or vulnerability?
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Simonetti G, Bruno S, Padella A, Tenti E, and Martinelli G
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- Animals, Carcinogenesis genetics, Humans, M Phase Cell Cycle Checkpoints genetics, Models, Genetic, Neoplasms pathology, Aneuploidy, Chromosomal Instability genetics, Gene Expression Regulation, Neoplastic, Neoplasms genetics, Spindle Apparatus genetics
- Abstract
Aneuploidy is a very rare and tissue-specific event in normal conditions, occurring in a low number of brain and liver cells. Its frequency increases in age-related disorders and is one of the hallmarks of cancer. Aneuploidy has been associated with defects in the spindle assembly checkpoint (SAC). However, the relationship between chromosome number alterations, SAC genes and tumor susceptibility remains unclear. Here, we provide a comprehensive review of SAC gene alterations at genomic and transcriptional level across human cancers and discuss the oncogenic and tumor suppressor functions of aneuploidy. SAC genes are rarely mutated but frequently overexpressed, with a negative prognostic impact on different tumor types. Both increased and decreased SAC gene expression show oncogenic potential in mice. SAC gene upregulation may drive aneuploidization and tumorigenesis through mitotic delay, coupled with additional oncogenic functions outside mitosis. The genomic background and environmental conditions influence the fate of aneuploid cells. Aneuploidy reduces cellular fitness. It induces growth and contact inhibition, mitotic and proteotoxic stress, cell senescence and production of reactive oxygen species. However, aneuploidy confers an evolutionary flexibility by favoring genome and chromosome instability (CIN), cellular adaptation, stem cell-like properties and immune escape. These properties represent the driving force of aneuploid cancers, especially under conditions of stress and pharmacological pressure, and are currently under investigation as potential therapeutic targets. Indeed, promising results have been obtained from synthetic lethal combinations exploiting CIN, mitotic defects, and aneuploidy-tolerating mechanisms as cancer vulnerability., (© 2018 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
- Published
- 2019
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32. Efficacy of Azacitidine in the treatment of adult patients aged 65 years or older with AML.
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Tenti E, Papayannidis C, Marconi G, Parisi S, Simonetti G, Paolini S, Sartor C, Ottaviani E, Testoni N, and Martinelli G
- Subjects
- Aged, Aged, 80 and over, Antimetabolites, Antineoplastic pharmacology, Azacitidine pharmacology, Clinical Trials as Topic methods, DNA Methylation drug effects, Epigenesis, Genetic drug effects, Humans, Leukemia, Myeloid, Acute diagnosis, Myelodysplastic Syndromes diagnosis, Myelodysplastic Syndromes drug therapy, Quality of Life, Treatment Outcome, Antimetabolites, Antineoplastic therapeutic use, Azacitidine therapeutic use, Leukemia, Myeloid, Acute drug therapy
- Abstract
Introduction: Therapy for acute myeloid leukemia (AML) in elderly populations (>65 years) is still a challenge for scientists and hematologists worldwide, and represents an urgent medical need. Notably, the identification and the recognition of molecular and epigenetic mechanisms involved in the pathogenesis of such a heterogeneous disease, are providing new tools for a more successful and 'targeted' approach. Azacitidine is a hypomethylating agent (HMA) with relevant activity in patients affected by myelodysplastic syndrome (MDS) and AML with low blast cells percentage (>30%), in terms of reduction of transfusion dependence, and improvement of quality of life. Areas covered: This review summarizes the mechanism of action, safety profile and efficacy of azacitidine in the field of elderly AML populations, providing up-to-date references on this subset of high-risk patients. Expert opinion: HMAs are the first successful treatment for elderly patients with high-risk MDS and are effective for some AML subtypes. Translational studies based on gene expression profiling and molecular sequencing, would be able to identify, in the near future, patients with a favorable profile of response to these compounds suggesting new potential treatment combinations also.
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- 2016
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33. Multicentric survey on dose reduction/interruption of cancer drug therapy in 12.472 patients: indicators of suspected adverse reactions.
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Casadei Gardini A, Tenti E, Masini C, Nanni O, Scarpi E, Valgiusti M, Restuccia S, Gallani ML, Palazzini S, Bianchini E, Menozzi S, Maugeri A, Amadori D, Minguzzi M, and Frassineti GL
- Subjects
- Capecitabine adverse effects, Docetaxel, Drug Administration Schedule, Humans, Niacinamide adverse effects, Niacinamide analogs & derivatives, Organoplatinum Compounds adverse effects, Oxaliplatin, Phenylurea Compounds adverse effects, Retrospective Studies, Sorafenib, Taxoids adverse effects, Treatment Outcome, Antineoplastic Agents adverse effects, Neoplasms drug therapy, Pharmacovigilance
- Abstract
Antiblastic drugs have a high number of potential side-effects. Paradoxically, according to the National Network of Pharmacovigilance, the number of reported adverse reactions to these agents is proportionally lower than that registered for non antiblastic drugs. Critical phenomena such as treatment interruptions and significant dose reductions within the first two months of use may be indicators of adverse drug reactions. The aim of the present study was to increase our knowledge of pharmacovigilance to facilitate the actions taken to improve the risk-benefit profile of cancer drugs and, consequently, their safety. This retrospective observational survey was carried out on prescriptions from 1st January 2012 to 31st December 2012.Dose reductions of more than 10% during the first 90 days of therapy were considered as a surrogate indicator of an adverse reaction. Dose interruptions during the first 60 days of therapy were taken into consideration. Of the12,472 patients 1,248 underwent a dose reduction. The drugs that most often required a dose reduction were paclitaxel and oxaliplatin (17.4% and 17.3%, respectively), docetaxel (14.8%), carboplatin (15%), fluorouracil (10.7%) and, among oral medications, capecitabine (6.9%). Of the 1896 patients treated with the same drugs, 9.7% interrupted treatment. Patients required a lower dose reduction than that reported by other authors. Around 15% of cases underwent a 30% dose reduction within three months of starting therapy, indicating a possible adverse reaction. Constant monitoring of dose prescription and continuous training of medical and nursing staff are clearly needed to increase awareness of the importance of reporting adverse events., Competing Interests: CONFLICTS OF INTERESTS The authors have no competing interests to declare.
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- 2016
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34. Inflammatory indexes as predictors of prognosis and bevacizumab efficacy in patients with metastatic colorectal cancer.
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Passardi A, Scarpi E, Cavanna L, Dall'Agata M, Tassinari D, Leo S, Bernardini I, Gelsomino F, Tamberi S, Brandes AA, Tenti E, Vespignani R, Frassineti GL, Amadori D, and De Giorgi U
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bevacizumab adverse effects, Blood Platelets, Colorectal Neoplasms blood, Colorectal Neoplasms mortality, Colorectal Neoplasms pathology, Disease Progression, Disease-Free Survival, Female, Humans, Italy, Kaplan-Meier Estimate, Lymphocyte Count, Male, Middle Aged, Neoplasm Metastasis, Patient Selection, Platelet Count, Predictive Value of Tests, Proportional Hazards Models, Prospective Studies, Time Factors, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bevacizumab therapeutic use, Colorectal Neoplasms drug therapy, Lymphocytes, Neutrophils
- Abstract
Background: To investigate the role of pre-treatment inflammatory indexes (II) as predictors of prognosis and treatment efficacy in patients with metastatic colorectal cancer mCRC randomized onto the prospective multicenter randomized ITACa (Italian Trial in Advanced Colorectal Cancer) trial to receive first-line chemotherapy (CT) with or without bevacizumab (Bev)., Results: In the overall population, PFS and OS were higher in patients with low SII (p = .015 and .002, respectively), low NLR (p = .0001 and <.0001, respectively) and low PLR (p = .004 and .008, respectively). Patients with low NLR in the CT plus Bev arm had a higher PFS than those treated with CT alone (HR = 0.69, p = .021)., Patients and Methods: Two hundred and eighty-nine patients were considered for this study, 141 receiving CT plus Bev and 148 receiving CT alone. The pre-treatment systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were evaluated to identify a potential correlation with progression-free (PFS) and overall survival (OS) in both the overall population and the 2 treatment arms., Conclusion: Our results indicate that II, in particular NLR, are good prognostic and predictive markers for mCRC patients who are candidates for CT plus Bev., Competing Interests: CONFICTS OF INTEREST The authors have declared that no competing interests exist.
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- 2016
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35. eNOS polymorphisms and clinical outcome in advanced HCC patients receiving sorafenib: final results of the ePHAS study.
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Casadei Gardini A, Marisi G, Faloppi L, Scarpi E, Foschi FG, Iavarone M, Lauletta G, Corbelli J, Valgiusti M, Facchetti F, Della Corte C, Neri LM, Tamberi S, Cascinu S, Scartozzi M, Amadori D, Nanni O, Tenti E, Ulivi P, and Frassineti GL
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Hepatocellular drug therapy, Carcinoma, Hepatocellular mortality, Case-Control Studies, Disease-Free Survival, Drug Resistance, Neoplasm genetics, Female, Genotype, Humans, Kaplan-Meier Estimate, Liver Neoplasms drug therapy, Liver Neoplasms mortality, Male, Middle Aged, Niacinamide therapeutic use, Retrospective Studies, Sorafenib, Antineoplastic Agents therapeutic use, Carcinoma, Hepatocellular genetics, Liver Neoplasms genetics, Niacinamide analogs & derivatives, Nitric Oxide Synthase Type III genetics, Phenylurea Compounds therapeutic use, Polymorphism, Single Nucleotide
- Abstract
Sorafenib may reduce endothelial nitric oxide synthase (eNOS) activity by inhibiting vascular endothelial growth factor receptors (VEGF-R), leading to a decrease in nitric oxide production. In the Italian multicenter ePHAS (eNOS polymorphisms in HCC and sorafenib) study, we analyzed the role of eNOS polymorphisms in relation to clinical outcome in patients with hepatocellular carcinoma (HCC) receiving sorafenib. Our retrospective study included a training cohort of 41 HCC patients and a validation cohort of 87 HCC patients, all undergoing sorafenib treatment. Three eNOS polymorphisms (eNOS -786T>C, eNOS VNTR 27bp 4a/b and eNOS+894G>T) were analyzed by direct sequencing or Real Time PCR in relation to progression-free survival (PFS) and overall survival (OS) (log-rank test). In univariate analysis, training cohort patients homozygous for eNOS haplotype (HT1:T-4b at eNOS-786/eNOS VNTR) had a lower median PFS (2.6 vs. 5.8 months, P < 0.0001) and OS (3.2 vs.14.6 months, P = 0.024) than those with other haplotypes. In the validation set, patients homozygous for HT1 had a lower median PFS (2.0 vs. 6.7 months, P < 0.0001) and OS (6.4 vs.18.0 months, P < 0.0001) than those with other haplotypes. Multivariate analysis confirmed this haplotype as the only independent prognostic factor. Our results suggest that haplotype HT1 in the eNOS gene may be capable of identifying a subset of HCC patients who are resistant to sorafenib., Competing Interests: The authors declare no conflicts of interest.
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- 2016
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36. Effects of metformin on clinical outcome in diabetic patients with advanced HCC receiving sorafenib.
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Casadei Gardini A, Marisi G, Scarpi E, Scartozzi M, Faloppi L, Silvestris N, Masi G, Vivaldi C, Brunetti O, Tamberi S, Foschi FG, Tamburini E, Tenti E, Ricca Rosellini S, Ulivi P, Cascinu S, Nanni O, and Frassineti GL
- Subjects
- Carcinoma, Hepatocellular complications, Diabetes Mellitus, Type 2 complications, Drug Resistance, Neoplasm, Humans, Liver Neoplasms complications, Niacinamide therapeutic use, Retrospective Studies, Sorafenib, Survival Analysis, Treatment Outcome, Antineoplastic Agents therapeutic use, Carcinoma, Hepatocellular drug therapy, Diabetes Mellitus, Type 2 drug therapy, Hypoglycemic Agents therapeutic use, Liver Neoplasms drug therapy, Metformin therapeutic use, Niacinamide analogs & derivatives, Phenylurea Compounds therapeutic use, Protein Kinase Inhibitors therapeutic use
- Abstract
Background and Objective: Several studies have reported an association between type 2 diabetes mellitus and hepatocellular carcinoma (HCC). Data from several retrospective studies and meta-analyses have highlighted a reduction of about 50% in the risk of developing HCC in cirrhotic patients treated with metformin for diabetes. The aim of this study was to evaluate the different outcomes of patients who received or did not receive metformin during treatment with sorafenib., Methods: We analyzed 93 patients consecutively treated with sorafenib. Forty-two (45.2%) patients were diabetic, of whom 31 were on metformin. Progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method and compared with the log-rank test., Results: The concomitant use of sorafenib and metformin was associated with a median PFS of 2.6 months (95% CI 1.9-3.3) compared to 5.0 months (95% CI 2.5-8.2) for patients receiving sorafenib alone (p = 0.029). The median OS of patients treated with the combination was 10.4 months (95% CI 3.9-14.4) compared to 15.1 months (95% CI 11.7-17.8) for those who were not given metformin (p = 0.014)., Conclusions: Our findings could be the result of increased tumor aggressiveness and resistance to sorafenib in metformin-treated patients.
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- 2015
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37. Long-term complete response in a patient with liver metastases from breast cancer treated with metronomic chemotherapy.
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Cecconetto L, Casadei Gardini A, Tenti E, Maltoni R, Bravaccini S, Oboldi D, Zoli W, Serra P, Donati C, Sarti S, Amadori D, and Rocca A
- Subjects
- Administration, Oral, Carcinoma, Ductal, Breast secondary, Cyclophosphamide administration & dosage, Doxorubicin administration & dosage, Female, Humans, Immunohistochemistry, Liver Neoplasms diagnosis, Maintenance Chemotherapy, Mastectomy, Modified Radical, Methotrexate administration & dosage, Middle Aged, Neoplasm Staging, Paclitaxel administration & dosage, Predictive Value of Tests, Tomography, X-Ray Computed, Treatment Outcome, Up-Regulation, Administration, Metronomic, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biomarkers, Tumor analysis, Carcinoma, Ductal, Breast drug therapy, Liver Neoplasms drug therapy, Liver Neoplasms secondary, Triple Negative Breast Neoplasms drug therapy, Triple Negative Breast Neoplasms pathology, Vascular Endothelial Growth Factor Receptor-2 analysis
- Abstract
Background: Preclinical studies have shown that several chemotherapeutic agents at low doses may affect the vascular system. Here we report the case of a patient with long-term cancer control by metronomic chemotherapy., Case Presentation: A 62-year-old woman with breast cancer underwent a left mastectomy in July 2007. For a liver metastasis she was given first-line chemotherapy with doxorubicin plus paclitaxel every 21 days. A CT scan after the sixth cycle showed a partial response. It was decided to stop the treatment with doxorubicin and paclitaxel, and start metronomic therapy with cyclophosphamide 50 mg daily orally and methotrexate 2.5 mg twice daily, 2 days a week. After 6 months of this maintenance treatment, CT scan showed a complete response. We examined the expression of vascular endothelial growth factor receptor 2 (VEGFR2) in histological sections of the primary tumor of our patient, finding evidence of overexpression of the receptor. The metronomic treatment is still ongoing, and after 60 months the patient maintains a complete response., Conclusion: This clinical case highlights how suitable metronomic chemotherapy can be used as maintenance therapy, allowing long-term treatment with no significant toxicity. This case suggests that the level of VEGFR2 is predictive of best response to antiangiogenic therapy.
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- 2014
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38. Separate episodes of capillary leak syndrome and pulmonary hypertension after adjuvant gemcitabine and three years later after nab-paclitaxel for metastatic disease.
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Casadei Gardini A, Aquilina M, Oboldi D, Lucchesi A, Carloni S, Tenti E, Burgio MA, Amadori D, and Frassineti GL
- Subjects
- Aged, Albumins administration & dosage, Albumins therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Capillary Leak Syndrome diagnosis, Chemotherapy, Adjuvant, Deoxycytidine administration & dosage, Deoxycytidine adverse effects, Deoxycytidine therapeutic use, Female, Humans, Hypertension, Pulmonary diagnosis, Paclitaxel administration & dosage, Paclitaxel therapeutic use, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms pathology, Time Factors, Tomography, X-Ray Computed, Ultrasonography, Doppler, Gemcitabine, Albumins adverse effects, Capillary Leak Syndrome etiology, Deoxycytidine analogs & derivatives, Hypertension, Pulmonary etiology, Paclitaxel adverse effects, Pancreatic Neoplasms complications
- Abstract
Background: Systemic capillary leak syndrome is a rare disease with a high mortality rate. This syndrome is characterised by generalised edema, hypotension, hemoconcentration, and hypoproteinemia. The cause is the sudden onset of capillary hyperpermeability with extravasations of plasma from the intravascular to the extravascular compartment. We present the case of a patient who experienced two episodes of systemic capillary leak syndrome and pulmonary hypertension; the first after gemcitabine in an adjuvant setting and the second three years later after treatment with nab-paclitaxel for metastatic disease., Case Presentation: A 65-year-old patient underwent a pancreatectomy in January 2010 for ductal carcinoma (pT3 N0 M0, stage IIa), followed by adjuvant chemotherapy. Seven days after the last cycle, she developed dyspnea associated with orthopnea and cough. A transthoracic cardiac ecocolordoppler was performed, with evidence of pulmonary hypertension (58 mmHg). Blood tests showed an increase in creatinine, pro-BNP and D-Dimer. She began high-dose diuretic therapy combined with cortisone. After a month, the patient was eupneic and the anasarca had resolved. We decided gradually to reduce the steroid and diuretic therapy. After ten days of the reduction, the patient began to re-present the same symptoms after treatment with gemcitabine. Corticosteroid therapy was restored with rapid clinical benefit and decreased pro-BNP after a week of treatment. After two years, the disease returned. As a first line treatment, it was decided to use nab-paclitaxel 100 mg/m2 weekly. After two doses, followed by approximately 14 days of treatment, the patient developed acute respiratory distress syndrome. The clinical suspicion was a relapse of capillary leak syndrome and treatment with a high-dose diuretic (furosemide 250 mg daily) was started combined with cortisone (40 mg methylprednisolone). The patient showed a progressive clinical benefit., Conclusions: In patients treated with gemcitabine and nab-paclitaxel who experience a sudden onset of diffuse edema with respiratory distress, capillary leak syndrome should be suspected. Immediate treatment with corticosteroids may be life-saving.
- Published
- 2013
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