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1. Correction to: Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting: evidence from the REPOSI Register (Internal and Emergency Medicine, (2023), 18, 4, (1049-1063), 10.1007/s11739-023-03254-3)

Author

Succurro E., Succurro, E, Novella, A, Nobili, A, Giofre, F, Arturi, F, Sciacqua, A, Andreozzi, F, Pietrangelo, A, Sesti, G, Perticone, F, Violi, F, Corrao, S, Marengoni, A, Tettamanti, M, Pasina, L, Franchi, C, Miglio, G, Ardoino, I, Cantiero, S, Prisco, D, Silvestri, E, Emmi, G, Bettiol, A, Mattioli, I, Mazzetti, M, Biolo, G, Zanetti, M, Bartelloni, G, Zaccari, M, Chiuch, M, Martini, I, Pirro, M, Lupattelli, G, Bianconi, V, Alcidi, R, Giotta, A, Mannarino, M, Girelli, D, Busti, F, Marchi, G, Barbagallo, M, Dominguez, L, Beneduce, V, Cacioppo, F, Natoli, G, Mularo, S, Raspanti, M, Argano, C, Cavallaro, F, Zoli, M, Orio, G, Magnolfi, E, Serafini, G, Brunori, M, Lazzari, I, Simili, A, Fabio, G, De Amicis, M, Luca, G, Scaramellini, N, Stefano, V, Leoni, S, Seghezzi, S, Di Mauro, A, Maira, D, Mancarella, M, Lucchi, T, Clerici, M, Bonini, G, Conti, F, Prolo, S, Fabrizi, M, Martelengo, M, Vigani, G, Nicolini, P, Sabatino, A, Miceli, E, Pisati, M, Pitotti, L, Antoci, V, Cambie, G, Pontremoli, R, Beccati, V, Nobili, G, Leoncini, G, Alberto, J, Cattaneo, F, Anastasio, L, Sofia, L, Carbone, M, Cipollone, F, Rossi, I, Valeriani, E, D'Ardes, D, Cipollone, A, Esposito, L, Sestili, S, Angelucci, E, Mancuso, G, Calipari, D, Bartone, M, Manetti, R, Sircana, M, Berria, M, Delitala, A, Muscaritoli, M, Molfino, A, Petrillo, E, Giorgi, A, Gracin, C, Imbimbo, G, Romanelli, G, Volpini, A, Lucente, D, Manzoni, F, Pirozzi, A, Zucchelli, A, Geneletti, T, Picardi, A, Bellelli, G, Corsi, M, Antonucci, C, Sidoli, C, Principato, G, Bonfanti, A, Szabo, H, Mazzola, P, Piazzoli, A, Tassone, B, De Falco, A, Negro, E, Brenna, M, Trotta, L, Fabris, F, Bertozzi, I, Bogoni, G, Prandini, T, Ratti, F, Zurlo, C, Cerruti, L, Cosi, E, Reni, E, Manfredini, R, Boari, B, Tiseo, R, Savrie, C, Fabbian, F, Paolisso, G, Catalano, C, Meo, I, Sabba, C, Suppressa, P, De Vincenzo, G, Comitangelo, A, Amoruso, E, Custodero, C, Re, G, Barnaba, I, Schilardi, A, Fenoglio, L, Falcetta, A, D'Aniano, S, Tiraboschi, S, Cespiati, A, Oberti, G, Sigon, G, Cinque, F, Colavolpe, L, Curra, J, Alletto, F, Benzoni, G, Peyvandi, F, Rossio, R, Colombo, G, Agosti, P, Pagliaro, E, Semproni, E, Canetta, C, Monzani, V, Savojardo, V, Ceriani, G, Folli, C, Tognin, T, Purrello, F, Pino, A, Piro, S, Rozzini, R, Falanga, L, Boffelli, S, Ferrandina, C, Mazzeo, F, Spazzini, E, Cono, G, Cesaroni, G, Perri, L, Guasti, L, Rotunno, F, Castiglioni, L, Maresca, A, Squizzato, A, Campiotti, L, Grossi, A, Dentali, F, Behnke, V, Perticone, M, Maio, R, Scozzafava, A, Condoleo, V, Clausi, E, Armentaro, G, Panza, A, Stanghellini, V, Ruggeri, E, Vecchio, S, Benzoni, I, Minisola, S, Colangelo, L, Cilli, M, Labbadia, G, Pepe, J, Castellino, P, Zanoli, L, Gaudio, A, Xourafa, A, Spichetti, C, Torre, S, Gennaro, A, Ballestrero, A, Ferrando, F, Gonella, R, Cerminara, D, Setti, P, Traversa, C, Scarsi, C, Famularo, G, Tarsitani, P, Morretti, T, Aglitti, A, Giacco, S, Firinu, D, Costanzo, G, Chessa, S, Montalto, G, Licata, A, Rizzo, A, Corica, F, Basile, G, Catalano, A, Bellone, F, Principato, C, Cocuzza, A, Mecocci, P, Ruggiero, C, Boccardi, V, Meschi, T, Ticinesi, A, Nouvenne, A, Pirisi, M, Sola, D, Bellan, M, Quadri, R, Larovere, E, Novelli, M, Simeone, E, Scurti, R, Tolloso, F, Tarquini, R, Valoriani, A, Dolenti, S, Vannini, G, Volpi, R, Bocchi, P, Vignali, A, Harari, S, Lonati, C, Napoli, F, Aiello, I, Salvatore, T, Monaco, L, Ricozzi, C, Coviello, F, Catalini, C, Pilotto, A, Indiano, I, Gandolfo, F, Gonella, D, Nuti, R, Valenti, R, Ruvio, M, Cappelli, S, Palazzuoli, A, Durante, V, Tirotta, D, Eusebi, G, Tresoldi, M, Bozzolo, E, Damanti, S, Porta, M, Gino, M, Pari, B, Pace, E, Succurro E., Novella A., Nobili A., Giofre F., Arturi F., Sciacqua A., Andreozzi F., Pietrangelo A., Sesti G., Perticone F., Violi F., Corrao S., Marengoni A., Tettamanti M., Pasina L., Franchi C., Miglio G., Ardoino I., Cantiero S., Prisco D., Silvestri E., Emmi G., Bettiol A., Mattioli I., Mazzetti M., Biolo G., Zanetti M., Bartelloni G., Zaccari M., Chiuch M., Martini I., Pirro M., Lupattelli G., Bianconi V., Alcidi R., Giotta A., Mannarino M. 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D., Maira D., Mancarella M., Lucchi T., Clerici M., Bonini G., Conti F., Prolo S., Fabrizi M., Martelengo M., Vigani G., Nicolini P., Sabatino A., Miceli E., Pisati M., Pitotti L., Antoci V., Cambie G., Pontremoli R., Beccati V., Nobili G., Leoncini G., Alberto J., Cattaneo F., Anastasio L., Sofia L., Carbone M., Cipollone F., Rossi I., Valeriani E., D'Ardes D., Cipollone A., Esposito L., Sestili S., Angelucci E., Mancuso G., Calipari D., Bartone M., Manetti R., Sircana M., Berria M., Delitala A., Muscaritoli M., Molfino A., Petrillo E., Giorgi A., Gracin C., Imbimbo G., Romanelli G., Volpini A., Lucente D., Manzoni F., Pirozzi A., Zucchelli A., Geneletti T., Picardi A., Bellelli G., Corsi M., Antonucci C., Sidoli C., Principato G., Bonfanti A., Szabo H., Mazzola P., Piazzoli A., Tassone B., De Falco A. B. T., Negro E., Brenna M., Trotta L., Fabris F., Bertozzi I., Bogoni G., Prandini T., Ratti F., Zurlo C., Cerruti L., Cosi E., Reni E., Manfredini R., Boari B., Tiseo R., Savrie C., Fabbian F., Paolisso G., Catalano C., Meo I., Sabba C., Suppressa P., De Vincenzo G. M., Comitangelo A., Amoruso E., Custodero C., Re G., Barnaba I., Schilardi A., Fenoglio L., Falcetta A., D'Aniano S., Tiraboschi S., Cespiati A., Oberti G., Sigon G., Cinque F., Colavolpe L., Curra J., Alletto F., Benzoni G., Peyvandi F., Rossio R., Colombo G., Agosti P., Pagliaro E., Semproni E., Canetta C., Monzani V., Savojardo V., Ceriani G., Folli C., Tognin T., Purrello F., Pino A., Piro S., Rozzini R., Falanga L., Boffelli S., Ferrandina C., Mazzeo F., Spazzini E., Cono G., Cesaroni G., Perri L., Guasti L., Rotunno F., Castiglioni L., Maresca A., Squizzato A., Campiotti L., Grossi A., Dentali F., Behnke V., Perticone M., Maio R., Scozzafava A., Condoleo V., Clausi E., Armentaro G., Panza A., Stanghellini V., Ruggeri E., Vecchio S., Benzoni I., Minisola S., Colangelo L., Cilli M., Labbadia G., Pepe J., Castellino P., Zanoli L., Gaudio A., Xourafa A., Spichetti C., Torre S., Gennaro A., Ballestrero A., Ferrando F., Gonella R., Cerminara D., Setti P., Traversa C., Scarsi C., Famularo G., Tarsitani P., Morretti T., Aglitti A., Giacco S., Firinu D., Costanzo G., Chessa S., Montalto G., Licata A., Rizzo A., Corica F., Basile G., Catalano A., Bellone F., Principato C., Cocuzza A., Mecocci P., Ruggiero C., Boccardi V., Meschi T., Ticinesi A., Nouvenne A., Pirisi M., Sola D., Bellan M., Quadri R., Larovere E., Novelli M., Simeone E., Scurti R., Tolloso F., Tarquini R., Valoriani A., Dolenti S., Vannini G., Volpi R., Bocchi P., Vignali A., Harari S., Lonati C., Napoli F., Aiello I., Salvatore T., Monaco L., Ricozzi C., Coviello F., Catalini C., Pilotto A., Indiano I., Gandolfo F., Gonella D., Nuti R., Valenti R., Ruvio M., Cappelli S., Palazzuoli A., Durante V., Tirotta D., Eusebi G., Tresoldi M., Bozzolo E., Damanti S., Porta M., Gino M., Pari B., Pace E., Succurro E., Succurro, E, Novella, A, Nobili, A, Giofre, F, Arturi, F, Sciacqua, A, Andreozzi, F, Pietrangelo, A, Sesti, G, Perticone, F, Violi, F, Corrao, S, Marengoni, A, Tettamanti, M, Pasina, L, Franchi, C, Miglio, G, Ardoino, I, Cantiero, S, Prisco, D, Silvestri, E, Emmi, G, Bettiol, A, Mattioli, I, Mazzetti, M, Biolo, G, Zanetti, M, Bartelloni, G, Zaccari, M, Chiuch, M, Martini, I, Pirro, M, Lupattelli, G, Bianconi, V, Alcidi, R, Giotta, A, Mannarino, M, Girelli, D, Busti, F, Marchi, G, Barbagallo, M, Dominguez, L, Beneduce, V, Cacioppo, F, Natoli, G, Mularo, S, Raspanti, M, Argano, C, Cavallaro, F, Zoli, M, Orio, G, Magnolfi, E, Serafini, G, Brunori, M, Lazzari, I, Simili, A, Fabio, G, De Amicis, M, Luca, G, Scaramellini, N, Stefano, V, Leoni, S, Seghezzi, S, Di Mauro, A, Maira, D, Mancarella, M, Lucchi, T, Clerici, M, Bonini, G, Conti, F, Prolo, S, Fabrizi, M, Martelengo, M, Vigani, G, Nicolini, P, Sabatino, A, Miceli, E, Pisati, M, Pitotti, L, Antoci, V, Cambie, G, Pontremoli, R, Beccati, V, Nobili, G, Leoncini, G, Alberto, J, Cattaneo, F, Anastasio, L, Sofia, L, Carbone, M, Cipollone, F, Rossi, I, Valeriani, E, D'Ardes, D, Cipollone, A, Esposito, L, Sestili, S, Angelucci, E, Mancuso, G, Calipari, D, Bartone, M, Manetti, R, Sircana, M, Berria, M, Delitala, A, Muscaritoli, M, Molfino, A, Petrillo, E, Giorgi, A, Gracin, C, Imbimbo, G, Romanelli, G, Volpini, A, Lucente, D, Manzoni, F, Pirozzi, A, Zucchelli, A, Geneletti, T, Picardi, A, Bellelli, G, Corsi, M, Antonucci, C, Sidoli, C, Principato, G, Bonfanti, A, Szabo, H, Mazzola, P, Piazzoli, A, Tassone, B, De Falco, A, Negro, E, Brenna, M, Trotta, L, Fabris, F, Bertozzi, I, Bogoni, G, Prandini, T, Ratti, F, Zurlo, C, Cerruti, L, Cosi, E, Reni, E, Manfredini, R, Boari, B, Tiseo, R, Savrie, C, Fabbian, F, Paolisso, G, Catalano, C, Meo, I, Sabba, C, Suppressa, P, De Vincenzo, G, Comitangelo, A, Amoruso, E, Custodero, C, Re, G, Barnaba, I, Schilardi, A, Fenoglio, L, Falcetta, A, D'Aniano, S, Tiraboschi, S, Cespiati, A, Oberti, G, Sigon, G, Cinque, F, Colavolpe, L, Curra, J, Alletto, F, Benzoni, G, Peyvandi, F, Rossio, R, Colombo, G, Agosti, P, Pagliaro, E, Semproni, E, Canetta, C, Monzani, V, Savojardo, V, Ceriani, G, Folli, C, Tognin, T, Purrello, F, Pino, A, Piro, S, Rozzini, R, Falanga, L, Boffelli, S, Ferrandina, C, Mazzeo, F, Spazzini, E, Cono, G, Cesaroni, G, Perri, L, Guasti, L, Rotunno, F, Castiglioni, L, Maresca, A, Squizzato, A, Campiotti, L, Grossi, A, Dentali, F, Behnke, V, Perticone, M, Maio, R, Scozzafava, A, Condoleo, V, Clausi, E, Armentaro, G, Panza, A, Stanghellini, V, Ruggeri, E, Vecchio, S, Benzoni, I, Minisola, S, Colangelo, L, Cilli, M, Labbadia, G, Pepe, J, Castellino, P, Zanoli, L, Gaudio, A, Xourafa, A, Spichetti, C, Torre, S, Gennaro, A, Ballestrero, A, Ferrando, F, Gonella, R, Cerminara, D, Setti, P, Traversa, C, Scarsi, C, Famularo, G, Tarsitani, P, Morretti, T, Aglitti, A, Giacco, S, Firinu, D, Costanzo, G, Chessa, S, Montalto, G, Licata, A, Rizzo, A, Corica, F, Basile, G, Catalano, A, Bellone, F, Principato, C, Cocuzza, A, Mecocci, P, Ruggiero, C, Boccardi, V, Meschi, T, Ticinesi, A, Nouvenne, A, Pirisi, M, Sola, D, Bellan, M, Quadri, R, Larovere, E, Novelli, M, Simeone, E, Scurti, R, Tolloso, F, Tarquini, R, Valoriani, A, Dolenti, S, Vannini, G, Volpi, R, Bocchi, P, Vignali, A, Harari, S, Lonati, C, Napoli, F, Aiello, I, Salvatore, T, Monaco, L, Ricozzi, C, Coviello, F, Catalini, C, Pilotto, A, Indiano, I, Gandolfo, F, Gonella, D, Nuti, R, Valenti, R, Ruvio, M, Cappelli, S, Palazzuoli, A, Durante, V, Tirotta, D, Eusebi, G, Tresoldi, M, Bozzolo, E, Damanti, S, Porta, M, Gino, M, Pari, B, Pace, E, Succurro E., Novella A., Nobili A., Giofre F., Arturi F., Sciacqua A., Andreozzi F., Pietrangelo A., Sesti G., Perticone F., Violi F., Corrao S., Marengoni A., Tettamanti M., Pasina L., Franchi C., Miglio G., Ardoino I., Cantiero S., Prisco D., Silvestri E., Emmi G., Bettiol A., Mattioli I., Mazzetti M., Biolo G., Zanetti M., Bartelloni G., Zaccari M., Chiuch M., Martini I., Pirro M., Lupattelli G., Bianconi V., Alcidi R., Giotta A., Mannarino M. R., Girelli D., Busti F., Marchi G., Barbagallo M., Dominguez L., Beneduce V., Cacioppo F., Natoli G., Mularo S., Raspanti M., Argano C., Cavallaro F., Zoli M., Orio G., Magnolfi E., Serafini G., Brunori M., Lazzari I., Simili A., Fabio G., De Amicis M. M., Luca G., Scaramellini N., Stefano V., Leoni S., Seghezzi S., Di Mauro A. D., Maira D., Mancarella M., Lucchi T., Clerici M., Bonini G., Conti F., Prolo S., Fabrizi M., Martelengo M., Vigani G., Nicolini P., Sabatino A., Miceli E., Pisati M., Pitotti L., Antoci V., Cambie G., Pontremoli R., Beccati V., Nobili G., Leoncini G., Alberto J., Cattaneo F., Anastasio L., Sofia L., Carbone M., Cipollone F., Rossi I., Valeriani E., D'Ardes D., Cipollone A., Esposito L., Sestili S., Angelucci E., Mancuso G., Calipari D., Bartone M., Manetti R., Sircana M., Berria M., Delitala A., Muscaritoli M., Molfino A., Petrillo E., Giorgi A., Gracin C., Imbimbo G., Romanelli G., Volpini A., Lucente D., Manzoni F., Pirozzi A., Zucchelli A., Geneletti T., Picardi A., Bellelli G., Corsi M., Antonucci C., Sidoli C., Principato G., Bonfanti A., Szabo H., Mazzola P., Piazzoli A., Tassone B., De Falco A. B. T., Negro E., Brenna M., Trotta L., Fabris F., Bertozzi I., Bogoni G., Prandini T., Ratti F., Zurlo C., Cerruti L., Cosi E., Reni E., Manfredini R., Boari B., Tiseo R., Savrie C., Fabbian F., Paolisso G., Catalano C., Meo I., Sabba C., Suppressa P., De Vincenzo G. M., Comitangelo A., Amoruso E., Custodero C., Re G., Barnaba I., Schilardi A., Fenoglio L., Falcetta A., D'Aniano S., Tiraboschi S., Cespiati A., Oberti G., Sigon G., Cinque F., Colavolpe L., Curra J., Alletto F., Benzoni G., Peyvandi F., Rossio R., Colombo G., Agosti P., Pagliaro E., Semproni E., Canetta C., Monzani V., Savojardo V., Ceriani G., Folli C., Tognin T., Purrello F., Pino A., Piro S., Rozzini R., Falanga L., Boffelli S., Ferrandina C., Mazzeo F., Spazzini E., Cono G., Cesaroni G., Perri L., Guasti L., Rotunno F., Castiglioni L., Maresca A., Squizzato A., Campiotti L., Grossi A., Dentali F., Behnke V., Perticone M., Maio R., Scozzafava A., Condoleo V., Clausi E., Armentaro G., Panza A., Stanghellini V., Ruggeri E., Vecchio S., Benzoni I., Minisola S., Colangelo L., Cilli M., Labbadia G., Pepe J., Castellino P., Zanoli L., Gaudio A., Xourafa A., Spichetti C., Torre S., Gennaro A., Ballestrero A., Ferrando F., Gonella R., Cerminara D., Setti P., Traversa C., Scarsi C., Famularo G., Tarsitani P., Morretti T., Aglitti A., Giacco S., Firinu D., Costanzo G., Chessa S., Montalto G., Licata A., Rizzo A., Corica F., Basile G., Catalano A., Bellone F., Principato C., Cocuzza A., Mecocci P., Ruggiero C., Boccardi V., Meschi T., Ticinesi A., Nouvenne A., Pirisi M., Sola D., Bellan M., Quadri R., Larovere E., Novelli M., Simeone E., Scurti R., Tolloso F., Tarquini R., Valoriani A., Dolenti S., Vannini G., Volpi R., Bocchi P., Vignali A., Harari S., Lonati C., Napoli F., Aiello I., Salvatore T., Monaco L., Ricozzi C., Coviello F., Catalini C., Pilotto A., Indiano I., Gandolfo F., Gonella D., Nuti R., Valenti R., Ruvio M., Cappelli S., Palazzuoli A., Durante V., Tirotta D., Eusebi G., Tresoldi M., Bozzolo E., Damanti S., Porta M., Gino M., Pari B., and Pace E.

Abstract

In this article the names of a few collaborators and some data in Table 5 were missing. It has been corrected. The original article has been corrected.

Published
2023

2. Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting: evidence from the REPOSI Register

Author

Succurro, E, Novella, A, Nobili, A, Giofre, F, Arturi, F, Sciacqua, A, Andreozzi, F, Pietrangelo, A, Sesti, G, Perticone, F, Violi, F, Corrao, S, Marengoni, A, Tettamanti, M, Pasina, L, Franchi, C, Miglio, G, Ardoino, I, Cantiero, S, Prisco, D, Silvestri, E, Emmi, G, Bettiol, A, Mattioli, I, Mazzetti, M, Biolo, G, Zanetti, M, Bartelloni, G, Zaccari, M, Chiuch, M, Martini, I, Pirro, M, Lupattelli, G, Bianconi, V, Alcidi, R, Giotta, A, Mannarino, M, Girelli, D, Busti, F, Marchi, G, Barbagallo, M, Dominguez, L, Beneduce, V, Cacioppo, F, Natoli, G, Mularo, S, Raspanti, M, Argano, C, Cavallaro, F, Zoli, M, Orio, G, Magnolfi, E, Serafini, G, Brunori, M, Lazzari, I, Simili, A, Fabio, G, De Amicis, M, Luca, G, Scaramellini, N, Stefano, V, Leoni, S, Seghezzi, S, Di Mauro, A, Maira, D, Mancarella, M, Lucchi, T, Clerici, M, Bonini, G, Conti, F, Prolo, S, Fabrizi, M, Martelengo, M, Vigani, G, Nicolini, P, Sabatino, A, Miceli, E, Pisati, M, Pitotti, L, Antoci, V, Cambie, G, Pontremoli, R, Beccati, V, Nobili, G, Leoncini, G, Alberto, J, Cattaneo, F, Anastasio, L, Sofia, L, Carbone, M, Cipollone, F, Rossi, I, Valeriani, E, D'Ardes, D, Cipollone, A, Esposito, L, Sestili, S, Angelucci, E, Mancuso, G, Calipari, D, Bartone, M, Manetti, R, Sircana, M, Berria, M, Delitala, A, Muscaritoli, M, Molfino, A, Petrillo, E, Giorgi, A, Gracin, C, Imbimbo, G, Romanelli, G, Volpini, A, Lucente, D, Manzoni, F, Pirozzi, A, Zucchelli, A, Geneletti, T, Picardi, A, Bellelli, G, Corsi, M, Antonucci, C, Sidoli, C, Principato, G, Bonfanti, A, Szabo, H, Mazzola, P, Piazzoli, A, Tassone, B, De Falco, A, Negro, E, Brenna, M, Trotta, L, Fabris, F, Bertozzi, I, Bogoni, G, Prandini, T, Ratti, F, Zurlo, C, Cerruti, L, Cosi, E, Reni, E, Manfredini, R, Boari, B, Tiseo, R, Savrie, C, Fabbian, F, Paolisso, G, Catalano, C, Meo, I, Sabba, C, Suppressa, P, De Vincenzo, G, Comitangelo, A, Amoruso, E, Custodero, C, Re, G, Barnaba, I, Schilardi, A, Fenoglio, L, Falcetta, A, D'Aniano, S, Tiraboschi, S, Cespiati, A, Oberti, G, Sigon, G, Cinque, F, Colavolpe, L, Curra, J, Alletto, F, Benzoni, G, Peyvandi, F, Rossio, R, Colombo, G, Agosti, P, Pagliaro, E, Semproni, E, Canetta, C, Monzani, V, Savojardo, V, Ceriani, G, Folli, C, Tognin, T, Purrello, F, Pino, A, Piro, S, Rozzini, R, Falanga, L, Boffelli, S, Ferrandina, C, Mazzeo, F, Spazzini, E, Cono, G, Cesaroni, G, Perri, L, Guasti, L, Rotunno, F, Castiglioni, L, Maresca, A, Squizzato, A, Campiotti, L, Grossi, A, Dentali, F, Behnke, V, Perticone, M, Maio, R, Scozzafava, A, Condoleo, V, Clausi, E, Armentaro, G, Panza, A, Stanghellini, V, Ruggeri, E, Vecchio, S, Benzoni, I, Minisola, S, Colangelo, L, Cilli, M, Labbadia, G, Pepe, J, Castellino, P, Zanoli, L, Gaudio, A, Xourafa, A, Spichetti, C, Torre, S, Gennaro, A, Ballestrero, A, Ferrando, F, Gonella, R, Cerminara, D, Setti, P, Traversa, C, Scarsi, C, Famularo, G, Tarsitani, P, Morretti, T, Aglitti, A, Giacco, S, Firinu, D, Costanzo, G, Chessa, S, Montalto, G, Licata, A, Rizzo, A, Corica, F, Basile, G, Catalano, A, Bellone, F, Principato, C, Cocuzza, A, Mecocci, P, Ruggiero, C, Boccardi, V, Meschi, T, Ticinesi, A, Nouvenne, A, Pirisi, M, Sola, D, Bellan, M, Quadri, R, Larovere, E, Novelli, M, Simeone, E, Scurti, R, Tolloso, F, Tarquini, R, Valoriani, A, Dolenti, S, Vannini, G, Volpi, R, Bocchi, P, Vignali, A, Harari, S, Lonati, C, Napoli, F, Aiello, I, Salvatore, T, Monaco, L, Ricozzi, C, Coviello, F, Catalini, C, Pilotto, A, Indiano, I, Gandolfo, F, Gonella, D, Nuti, R, Valenti, R, Ruvio, M, Cappelli, S, Palazzuoli, A, Durante, V, Tirotta, D, Eusebi, G, Tresoldi, M, Bozzolo, E, Damanti, S, Porta, M, Gino, M, Pari, B, Pace, E, Succurro E., Novella A., Nobili A., Giofre F., Arturi F., Sciacqua A., Andreozzi F., Pietrangelo A., Sesti G., Perticone F., Violi F., Corrao S., Marengoni A., Tettamanti M., Pasina L., Franchi C., Miglio G., Ardoino I., Cantiero S., Prisco D., Silvestri E., Emmi G., Bettiol A., Mattioli I., Mazzetti M., Biolo G., Zanetti M., Bartelloni G., Zaccari M., Chiuch M., Martini I., Pirro M., Lupattelli G., Bianconi V., Alcidi R., Giotta A., Mannarino M. R., Girelli D., Busti F., Marchi G., Barbagallo M., Dominguez L., Beneduce V., Cacioppo F., Natoli G., Mularo S., Raspanti M., Argano C., Cavallaro F., Zoli M., Orio G., Magnolfi E., Serafini G., Brunori M., Lazzari I., Simili A., Fabio G., De Amicis M. M., Luca G., Scaramellini N., Stefano V., Leoni S., Seghezzi S., Di Mauro A. D., Maira D., Mancarella M., Lucchi T., Clerici M., Bonini G., Conti F., Prolo S., Fabrizi M., Martelengo M., Vigani G., Nicolini P., Sabatino A., Miceli E., Pisati M., Pitotti L., Antoci V., Cambie G., Pontremoli R., Beccati V., Nobili G., Leoncini G., Alberto J., Cattaneo F., Anastasio L., Sofia L., Carbone M., Cipollone F., Rossi I., Valeriani E., D'Ardes D., Cipollone A., Esposito L., Sestili S., Angelucci E., Mancuso G., Calipari D., Bartone M., Manetti R., Sircana M., Berria M., Delitala A., Muscaritoli M., Molfino A., Petrillo E., Giorgi A., Gracin C., Imbimbo G., Romanelli G., Volpini A., Lucente D., Manzoni F., Pirozzi A., Zucchelli A., Geneletti T., Picardi A., Bellelli G., Corsi M., Antonucci C., Sidoli C., Principato G., Bonfanti A., Szabo H., Mazzola P., Piazzoli A., Tassone B., De Falco A. B. T., Negro E., Brenna M., Trotta L., Fabris F., Bertozzi I., Bogoni G., Prandini T., Ratti F., Zurlo C., Cerruti L., Cosi E., Reni E., Manfredini R., Boari B., Tiseo R., Savrie C., Fabbian F., Paolisso G., Catalano C., Meo I., Sabba C., Suppressa P., De Vincenzo G. M., Comitangelo A., Amoruso E., Custodero C., Re G., Barnaba I., Schilardi A., Fenoglio L., Falcetta A., D'Aniano S., Tiraboschi S., Cespiati A., Oberti G., Sigon G., Cinque F., Colavolpe L., Curra J., Alletto F., Benzoni G., Peyvandi F., Rossio R., Colombo G., Agosti P., Pagliaro E., Semproni E., Canetta C., Monzani V., Savojardo V., Ceriani G., Folli C., Tognin T., Purrello F., Pino A., Piro S., Rozzini R., Falanga L., Boffelli S., Ferrandina C., Mazzeo F., Spazzini E., Cono G., Cesaroni G., Perri L., Guasti L., Rotunno F., Castiglioni L., Maresca A., Squizzato A., Campiotti L., Grossi A., Dentali F., Behnke V., Perticone M., Maio R., Scozzafava A., Condoleo V., Clausi E., Armentaro G., Panza A., Stanghellini V., Ruggeri E., Vecchio S., Benzoni I., Minisola S., Colangelo L., Cilli M., Labbadia G., Pepe J., Castellino P., Zanoli L., Gaudio A., Xourafa A., Spichetti C., Torre S., Gennaro A., Ballestrero A., Ferrando F., Gonella R., Cerminara D., Setti P., Traversa C., Scarsi C., Famularo G., Tarsitani P., Morretti T., Aglitti A., Giacco S., Firinu D., Costanzo G., Chessa S., Montalto G., Licata A., Rizzo A., Corica F., Basile G., Catalano A., Bellone F., Principato C., Cocuzza A., Mecocci P., Ruggiero C., Boccardi V., Meschi T., Ticinesi A., Nouvenne A., Pirisi M., Sola D., Bellan M., Quadri R., Larovere E., Novelli M., Simeone E., Scurti R., Tolloso F., Tarquini R., Valoriani A., Dolenti S., Vannini G., Volpi R., Bocchi P., Vignali A., Harari S., Lonati C., Napoli F., Aiello I., Salvatore T., Monaco L., Ricozzi C., Coviello F., Catalini C., Pilotto A., Indiano I., Gandolfo F., Gonella D., Nuti R., Valenti R., Ruvio M., Cappelli S., Palazzuoli A., Durante V., Tirotta D., Eusebi G., Tresoldi M., Bozzolo E., Damanti S., Porta M., Gino M., Pari B., Pace E., Succurro, E, Novella, A, Nobili, A, Giofre, F, Arturi, F, Sciacqua, A, Andreozzi, F, Pietrangelo, A, Sesti, G, Perticone, F, Violi, F, Corrao, S, Marengoni, A, Tettamanti, M, Pasina, L, Franchi, C, Miglio, G, Ardoino, I, Cantiero, S, Prisco, D, Silvestri, E, Emmi, G, Bettiol, A, Mattioli, I, Mazzetti, M, Biolo, G, Zanetti, M, Bartelloni, G, Zaccari, M, Chiuch, M, Martini, I, Pirro, M, Lupattelli, G, Bianconi, V, Alcidi, R, Giotta, A, Mannarino, M, Girelli, D, Busti, F, Marchi, G, Barbagallo, M, Dominguez, L, Beneduce, V, Cacioppo, F, Natoli, G, Mularo, S, Raspanti, M, Argano, C, Cavallaro, F, Zoli, M, Orio, G, Magnolfi, E, Serafini, G, Brunori, M, Lazzari, I, Simili, A, Fabio, G, De Amicis, M, Luca, G, Scaramellini, N, Stefano, V, Leoni, S, Seghezzi, S, Di Mauro, A, Maira, D, Mancarella, M, Lucchi, T, Clerici, M, Bonini, G, Conti, F, Prolo, S, Fabrizi, M, Martelengo, M, Vigani, G, Nicolini, P, Sabatino, A, Miceli, E, Pisati, M, Pitotti, L, Antoci, V, Cambie, G, Pontremoli, R, Beccati, V, Nobili, G, Leoncini, G, Alberto, J, Cattaneo, F, Anastasio, L, Sofia, L, Carbone, M, Cipollone, F, Rossi, I, Valeriani, E, D'Ardes, D, Cipollone, A, Esposito, L, Sestili, S, Angelucci, E, Mancuso, G, Calipari, D, Bartone, M, Manetti, R, Sircana, M, Berria, M, Delitala, A, Muscaritoli, M, Molfino, A, Petrillo, E, Giorgi, A, Gracin, C, Imbimbo, G, Romanelli, G, Volpini, A, Lucente, D, Manzoni, F, Pirozzi, A, Zucchelli, A, Geneletti, T, Picardi, A, Bellelli, G, Corsi, M, Antonucci, C, Sidoli, C, Principato, G, Bonfanti, A, Szabo, H, Mazzola, P, Piazzoli, A, Tassone, B, De Falco, A, Negro, E, Brenna, M, Trotta, L, Fabris, F, Bertozzi, I, Bogoni, G, Prandini, T, Ratti, F, Zurlo, C, Cerruti, L, Cosi, E, Reni, E, Manfredini, R, Boari, B, Tiseo, R, Savrie, C, Fabbian, F, Paolisso, G, Catalano, C, Meo, I, Sabba, C, Suppressa, P, De Vincenzo, G, Comitangelo, A, Amoruso, E, Custodero, C, Re, G, Barnaba, I, Schilardi, A, Fenoglio, L, Falcetta, A, D'Aniano, S, Tiraboschi, S, Cespiati, A, Oberti, G, Sigon, G, Cinque, F, Colavolpe, L, Curra, J, Alletto, F, Benzoni, G, Peyvandi, F, Rossio, R, Colombo, G, Agosti, P, Pagliaro, E, Semproni, E, Canetta, C, Monzani, V, Savojardo, V, Ceriani, G, Folli, C, Tognin, T, Purrello, F, Pino, A, Piro, S, Rozzini, R, Falanga, L, Boffelli, S, Ferrandina, C, Mazzeo, F, Spazzini, E, Cono, G, Cesaroni, G, Perri, L, Guasti, L, Rotunno, F, Castiglioni, L, Maresca, A, Squizzato, A, Campiotti, L, Grossi, A, Dentali, F, Behnke, V, Perticone, M, Maio, R, Scozzafava, A, Condoleo, V, Clausi, E, Armentaro, G, Panza, A, Stanghellini, V, Ruggeri, E, Vecchio, S, Benzoni, I, Minisola, S, Colangelo, L, Cilli, M, Labbadia, G, Pepe, J, Castellino, P, Zanoli, L, Gaudio, A, Xourafa, A, Spichetti, C, Torre, S, Gennaro, A, Ballestrero, A, Ferrando, F, Gonella, R, Cerminara, D, Setti, P, Traversa, C, Scarsi, C, Famularo, G, Tarsitani, P, Morretti, T, Aglitti, A, Giacco, S, Firinu, D, Costanzo, G, Chessa, S, Montalto, G, Licata, A, Rizzo, A, Corica, F, Basile, G, Catalano, A, Bellone, F, Principato, C, Cocuzza, A, Mecocci, P, Ruggiero, C, Boccardi, V, Meschi, T, Ticinesi, A, Nouvenne, A, Pirisi, M, Sola, D, Bellan, M, Quadri, R, Larovere, E, Novelli, M, Simeone, E, Scurti, R, Tolloso, F, Tarquini, R, Valoriani, A, Dolenti, S, Vannini, G, Volpi, R, Bocchi, P, Vignali, A, Harari, S, Lonati, C, Napoli, F, Aiello, I, Salvatore, T, Monaco, L, Ricozzi, C, Coviello, F, Catalini, C, Pilotto, A, Indiano, I, Gandolfo, F, Gonella, D, Nuti, R, Valenti, R, Ruvio, M, Cappelli, S, Palazzuoli, A, Durante, V, Tirotta, D, Eusebi, G, Tresoldi, M, Bozzolo, E, Damanti, S, Porta, M, Gino, M, Pari, B, Pace, E, Succurro E., Novella A., Nobili A., Giofre F., Arturi F., Sciacqua A., Andreozzi F., Pietrangelo A., Sesti G., Perticone F., Violi F., Corrao S., Marengoni A., Tettamanti M., Pasina L., Franchi C., Miglio G., Ardoino I., Cantiero S., Prisco D., Silvestri E., Emmi G., Bettiol A., Mattioli I., Mazzetti M., Biolo G., Zanetti M., Bartelloni G., Zaccari M., Chiuch M., Martini I., Pirro M., Lupattelli G., Bianconi V., Alcidi R., Giotta A., Mannarino M. R., Girelli D., Busti F., Marchi G., Barbagallo M., Dominguez L., Beneduce V., Cacioppo F., Natoli G., Mularo S., Raspanti M., Argano C., Cavallaro F., Zoli M., Orio G., Magnolfi E., Serafini G., Brunori M., Lazzari I., Simili A., Fabio G., De Amicis M. M., Luca G., Scaramellini N., Stefano V., Leoni S., Seghezzi S., Di Mauro A. D., Maira D., Mancarella M., Lucchi T., Clerici M., Bonini G., Conti F., Prolo S., Fabrizi M., Martelengo M., Vigani G., Nicolini P., Sabatino A., Miceli E., Pisati M., Pitotti L., Antoci V., Cambie G., Pontremoli R., Beccati V., Nobili G., Leoncini G., Alberto J., Cattaneo F., Anastasio L., Sofia L., Carbone M., Cipollone F., Rossi I., Valeriani E., D'Ardes D., Cipollone A., Esposito L., Sestili S., Angelucci E., Mancuso G., Calipari D., Bartone M., Manetti R., Sircana M., Berria M., Delitala A., Muscaritoli M., Molfino A., Petrillo E., Giorgi A., Gracin C., Imbimbo G., Romanelli G., Volpini A., Lucente D., Manzoni F., Pirozzi A., Zucchelli A., Geneletti T., Picardi A., Bellelli G., Corsi M., Antonucci C., Sidoli C., Principato G., Bonfanti A., Szabo H., Mazzola P., Piazzoli A., Tassone B., De Falco A. B. T., Negro E., Brenna M., Trotta L., Fabris F., Bertozzi I., Bogoni G., Prandini T., Ratti F., Zurlo C., Cerruti L., Cosi E., Reni E., Manfredini R., Boari B., Tiseo R., Savrie C., Fabbian F., Paolisso G., Catalano C., Meo I., Sabba C., Suppressa P., De Vincenzo G. M., Comitangelo A., Amoruso E., Custodero C., Re G., Barnaba I., Schilardi A., Fenoglio L., Falcetta A., D'Aniano S., Tiraboschi S., Cespiati A., Oberti G., Sigon G., Cinque F., Colavolpe L., Curra J., Alletto F., Benzoni G., Peyvandi F., Rossio R., Colombo G., Agosti P., Pagliaro E., Semproni E., Canetta C., Monzani V., Savojardo V., Ceriani G., Folli C., Tognin T., Purrello F., Pino A., Piro S., Rozzini R., Falanga L., Boffelli S., Ferrandina C., Mazzeo F., Spazzini E., Cono G., Cesaroni G., Perri L., Guasti L., Rotunno F., Castiglioni L., Maresca A., Squizzato A., Campiotti L., Grossi A., Dentali F., Behnke V., Perticone M., Maio R., Scozzafava A., Condoleo V., Clausi E., Armentaro G., Panza A., Stanghellini V., Ruggeri E., Vecchio S., Benzoni I., Minisola S., Colangelo L., Cilli M., Labbadia G., Pepe J., Castellino P., Zanoli L., Gaudio A., Xourafa A., Spichetti C., Torre S., Gennaro A., Ballestrero A., Ferrando F., Gonella R., Cerminara D., Setti P., Traversa C., Scarsi C., Famularo G., Tarsitani P., Morretti T., Aglitti A., Giacco S., Firinu D., Costanzo G., Chessa S., Montalto G., Licata A., Rizzo A., Corica F., Basile G., Catalano A., Bellone F., Principato C., Cocuzza A., Mecocci P., Ruggiero C., Boccardi V., Meschi T., Ticinesi A., Nouvenne A., Pirisi M., Sola D., Bellan M., Quadri R., Larovere E., Novelli M., Simeone E., Scurti R., Tolloso F., Tarquini R., Valoriani A., Dolenti S., Vannini G., Volpi R., Bocchi P., Vignali A., Harari S., Lonati C., Napoli F., Aiello I., Salvatore T., Monaco L., Ricozzi C., Coviello F., Catalini C., Pilotto A., Indiano I., Gandolfo F., Gonella D., Nuti R., Valenti R., Ruvio M., Cappelli S., Palazzuoli A., Durante V., Tirotta D., Eusebi G., Tresoldi M., Bozzolo E., Damanti S., Porta M., Gino M., Pari B., and Pace E.

Abstract

Diabetes is an increasing global health burden with the highest prevalence (24.0%) observed in elderly people. Older diabetic adults have a greater risk of hospitalization and several geriatric syndromes than older nondiabetic adults. For these conditions, special care is required in prescribing therapies including anti- diabetes drugs. Aim of this study was to evaluate the appropriateness and the adherence to safety recommendations in the prescriptions of glucose-lowering drugs in hospitalized elderly patients with diabetes. Data for this cross-sectional study were obtained from the REgistro POliterapie–Società Italiana Medicina Interna (REPOSI) that collected clinical information on patients aged ≥ 65 years acutely admitted to Italian internal medicine and geriatric non-intensive care units (ICU) from 2010 up to 2019. Prescription appropriateness was assessed according to the 2019 AGS Beers Criteria and anti-diabetes drug data sheets.Among 5349 patients, 1624 (30.3%) had diagnosis of type 2 diabetes. At admission, 37.7% of diabetic patients received treatment with metformin, 37.3% insulin therapy, 16.4% sulfonylureas, and 11.4% glinides. Surprisingly, only 3.1% of diabetic patients were treated with new classes of anti- diabetes drugs. According to prescription criteria, at admission 15.4% of patients treated with metformin and 2.6% with sulfonylureas received inappropriately these treatments. At discharge, the inappropriateness of metformin therapy decreased (10.2%, P < 0.0001). According to Beers criteria, the inappropriate prescriptions of sulfonylureas raised to 29% both at admission and at discharge. This study shows a poor adherence to current guidelines on diabetes management in hospitalized elderly people with a high prevalence of inappropriate use of sulfonylureas according to the Beers criteria.

Published
2023

3. CXCR3 and (alpha sub E beta sub 7) integrin identify a subset of CD8+ mature thymocytes that share phenotypic and functional properties with CD8+ gut intraepithelial lymphocytes

Author

Annunziato, F., Cosmi, L., Liotta, F., Lazzeri, E., Ramagnani, P., Angeli, R., Lasagni, L., Manetti, R., Marra, F., Gerard, C., Petrai, I., Dello Sbarba, P., Tonelli, F., Maggi, E., and Romagnani, S.

Subjects
CD8 lymphocytes -- Research, Integrins -- Research, Gastrointestinal mucosa -- Physiological aspects, Gastrointestinal mucosa -- Research, Health
Published
2006

5. Declining Prevalence of HIV-1 Drug Resistance in Antiretroviral Treatment-exposed Individuals in Western Europe

Author

De Luca, A, Dunn, D, Zazzi, M, Camacho, R, Torti, C, Fanti, I, Kaiser, R, Sönnerborg, A, Codoñer, Fm, Van Laethem, K, Vandamme, Am, Bansi, L, Ghisetti, V, van de Vijver DA, Asboe, D, Prosperi, Mc, Di Giambenedetto, S, Collaborators: Giacometti A, SEHERE collaboration in C. h. a. i. n., Butini, L, del Gobbo, R, Menzo, S, Tacconi, D, Corbelli, G, Zanussi, S, Monno, L, Punzi, G, Maggiolo, F, Callegaro, A, Calza, L, Pristerà, R, Turconi, P, Mandas, A, Tini, S, Zoncada, A, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Corsi, P, Galli, L, Di Pietro, M, Bartalesi, F, Colao, G, Tosti, A, Di Biagio, A, Setti, M, Bruzzone, B, Penco, G, Trezzi, M, Orani, A, Pardelli, R, De Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, Monforte, Ad, Cicconi, P, Rusconi, S, Gismondo, Mr, Micheli, V, Biondi, Ml, Gianotti, N, Capetti, A, Meraviglia, P, Boeri, E, Mussini, C, Pecorari, M, Soria, A, Vecchi, L, Santirocchi, M, Brustia, D, Ravanini, P, Dal Bello, F, Romano, N, Mancuso, S, Calzetti, C, Maserati, R, Filice, G, Baldanti, F, Francisci, D, Parruti, G, Polilli, E, Sacchini, D, Martinelli, C, Consolini, Rita, De Luca, A, Dunn, D, Zazzi, M, Camacho, R, Torti, C, Fanti, I, Kaiser, R, Sönnerborg, A, Codoñer, F, Van Laethem, K, Vandamme, A, Bansi, L, Ghisetti, V, Van De Vijver, D, Asboe, D, Prosperi, M, Di Giambenedetto, S, Mancuso, S, and Virology

Subjects
Male, Multivariate analysis, Databases, Factual, Drug Resistance, HIV Infections, Drug resistance, 0302 clinical medicine, Retrospective Studie, Risk Factors, Epidemiology, Genotype, pol Gene Products, Human Immunodeficiency Viru, Odds Ratio, Prevalence, Immunology and Allergy, HIV Infection, 030212 general & internal medicine, pol Gene Products, Viral, Multivariate Analysi, media_common, 0303 health sciences, Drug Resistance Prevalence HIV-1, Middle Aged, Resistance mutation, 3. Good health, Reverse Transcriptase Inhibitor, Europe, Infectious Diseases, Reverse Transcriptase Inhibitors, epidemiology, Female, Multiple, Human Immunodeficiency Virus, Human, Drug, Adult, medicine.medical_specialty, Evolution, media_common.quotation_subject, Sexual Behavior, antiretroviral therapy, Infectious Disease, Biology, Settore MED/17 - MALATTIE INFETTIVE, Evolution, Molecular, 03 medical and health sciences, Databases, SDG 3 - Good Health and Well-being, Drug Resistance, Multiple, Viral, medicine, Humans, HIV Protease Inhibitor, Factual, Retrospective Studies, 030306 microbiology, Risk Factor, Molecular, Retrospective cohort study, Odds ratio, HIV Protease Inhibitors, CD4 Lymphocyte Count, drug resistance, genotyping, HIV-1, Multivariate Analysis, Mutation, pol Gene Products, Human Immunodeficiency Virus, Immunology, Demography
Abstract

HIV-1 drug resistance represents a major obstacle to infection and disease control. This retrospective study analyzes trends and determinants of resistance in antiretroviral treatment (ART)-exposed individuals across 7 countries in Europe. Of 20 323 cases, 80% carried at least one resistance mutation: these declined from 81% in 1997 to 71% in 2008. Predicted extensive 3-class resistance was rare (3.2% considering the cumulative genotype) and peaked at 4.5% in 2005, decreasing thereafter. The proportion of cases exhausting available drug options dropped from 32% in 2000 to 1% in 2008. Reduced risk of resistance over calendar years was confirmed by multivariable analysis. © 2013 The Author.

Published
2013
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7. Laparoscopic Appendectomy Performed by Residents and Experienced Surgeons

Author

Bencini L, Bernini M, Martini F, Rossi M, Tommasi C, Miranda E, Luis Jose' SANCHEZ, Naspetti R, Manetti R, Ferrara A, Nesi S, Boffi B, Farsi M, and Moretti R

Subjects
Adult, Aged, 80 and over, Male, Chi-Square Distribution, Adolescent, Residents, Internship and Residency, Middle Aged, Statistics, Nonparametric, Trainees, Postoperative Complications, Treatment Outcome, Laparoscopic appendectomy, Scientific Papers, Appendectomy, Humans, Female, Laparoscopy, Clinical Competence, Safety, Indications, Aged
Abstract

Background: Laparoscopic appendectomy is widely performed by surgical residents, but its changing indications and outcomes have been poorly investigated. The aim of this study was to examine whether a difference exists in indications and outcomes between laparoscopic appendectomies performed by residents and those performed by experienced surgeons. Methods: Between 1999 and 2007, 218 laparoscopic appendectomies were performed and recorded. Data were analyzed to compare operations performed by residents with those by experienced surgeons in terms of indications for surgery and severity of disease. Moreover, laparoscopic appendectomies were thoroughly compared regarding outcomes and complications. Results: The residents had fewer conversions with laparoscopic appendectomy (8% vs 17%, P=0.04), and similar complication rates (12% vs 13%, P=0.16), compared with experienced surgeons. The median operating time was also comparable (67 minutes vs 60 minutes, P=0.23). However, patients operated on by residents had more emergencies (86% vs 70%, P=0.009), included more foreigners (27% vs 15%, P=0.03), and had intermediate to severe diseases, (81 vs 52%, P

Published
2009

8. Genotypic resistance profiles associated with virological failure to darunavir-containing regimens: a cross-sectional analysis

Author

Sterrantino, G, Zaccarelli, M, Colao, G, Baldanti, F, Di Giambenedetto, S, Carli, T, Maggiolo, F, Zazzi, M, Giacometti, A, Butini, L, Del Gobbo, R, Bagnarelli, P, Tacconi, D, Corbelli, G, Zanussi, S, Monno, L, Punzi, G, Callegaro, A, Calza, L, Re, MC, Pristera, R, Turconi, P, Mandas, A, Tini, S, Zoncada, A, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Corsi, P, Galli, L, Di Pietro, M, Bartalesi, F, Tosti, A, Di Biagio, A, Setti, M, Bruzzone, B, di Biagio, A, Penco, G, Trezzi, M, Orani, A, Pardelli, R, Arcidiacono, I, Degiuli, A, de Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, Cicconi, P, Rusconi, S, Gismondo, MR, Micheli, V, Biondi ML, Gianotti, N, Capetti, A, Meraviglia, P, Boeri, E, Mussini, C, Pecorari, M, Soria, A, Vecchi, L, Gerardo, AO, Santirocchi, M, Brustia, D, Maggiore, AO, Ravanini, P, Bello, FD, Romano, N, MANCUSO, Salvatrice, Calzetti, C, Maserati, R, Filice, G, Francisci, D, Parruti, G, Polilli, E, Sacchini, D, Martinelli, C, Consolini, R, Vatteroni, L, Vivarelli, A, Nerli, A, Lenzi, L, Magnani, G, Ortolani, P, Andreoni, M, Palamara, G, Fimiani, C, Palmisano, L, di Giambenedetto, S, Colafigli, M, Vullo, V, Turriziani, O, Montano, M, Antinori, A, Dentone, C, Gonnelli, A, de Luca, A, Palumbo, M, Ghisetti, V, Bonora, S, Foglie, PD, Rossi, C, Mondino, V, Malena, M, Grossi, P, Seminari, E, Poletti, F., Sterrantino, G, Zaccarelli, M, Colao, G, Baldanti, F, Di Giambenedetto, S, Carli, T, Maggiolo, F, Zazzi, M, Giacometti, A, Butini, L, Del Gobbo, R, Bagnarelli, P, Tacconi, D, Corbelli, G, Zanussi, S, Monno, L, Punzi, G, Callegaro, A, Calza, L, Re, MC, Pristera, R, Turconi, P, Mandas, A, Tini, S, Zoncada, A, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Corsi, P, Galli, L, Di Pietro, M, Bartalesi, F, Tosti, A, Di Biagio, A, Setti, M, Bruzzone, B, di Biagio, A, Penco, G, Trezzi, M, Orani, A, Pardelli, R, Arcidiacono, I, Degiuli, A, de Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, Cicconi, P, Rusconi, S, Gismondo, MR, Micheli, V, Biondi ML, Gianotti, N, Capetti, A, Meraviglia, P, Boeri, E, Mussini, C, Pecorari, M, Soria, A, Vecchi, L, Gerardo, AO, Santirocchi, M, Brustia, D, Maggiore, AO, Ravanini, P, Bello, FD, Romano, N, Mancuso, S, Calzetti, C, Maserati, R, Filice, G, Francisci, D, Parruti, G, Polilli, E, Sacchini, D, Martinelli, C, Consolini, R, Vatteroni, L, Vivarelli, A, Nerli, A, Lenzi, L, Magnani, G, Ortolani, P, Andreoni, M, Palamara, G, Fimiani, C, Palmisano, L, di Giambenedetto, S, Colafigli, M, Vullo, V, Turriziani, O, Montano, M, Antinori, A, Dentone, C, Gonnelli, A, de Luca, A, Palumbo, M, Ghisetti, V, Bonora, S, Foglie, PD, Rossi, C, Mondino, V, Malena, M, Grossi, P, Seminari, E, and Poletti, F

Subjects
Male, Time Factors, Cross-sectional study, Human immunodeficiency virus (HIV), Drug Resistance, HIV Infections, Drug resistance, medicine.disease_cause, Cohort Studies, Antiretroviral Therapy, Highly Active, Ritonavir-boosted darunavir, Genotype, HIV Infection, Treatment Failure, Viral, Genotypic resistance, Darunavir, Sulfonamides, General Medicine, Middle Aged, Virological failure, Infectious Diseases, Female, Human, medicine.drug, Adult, Microbiology (medical), Logistic Model, Time Factor, Antiretroviral Therapy, Settore MED/17 - MALATTIE INFETTIVE, Sulfonamide, Drug Resistance, Viral, medicine, Humans, Highly Active, Protease inhibitors, Cross-Sectional Studies, HIV Protease Inhibitors, HIV-1, Logistic Models, Mutation, HIV Protease Inhibitor, Cross-Sectional Studie, business.industry, Antiretroviral therapy, Virology, Protease inhibitor, Cohort Studie, business
Abstract

Introduction: This study aimed at defining protease (PR) resistance mutations associated with darunavir (DRV) failure and PR resistance evolution at DRV failure in a large database of treatment-experienced human immunodeficiency virus (HIV) patients. Results: Overall, 1,104 patients were included: 118 (10.7%) failed at a median observation time of 16 months. The mean number of PR mutations at baseline was 2.7, but it was higher in patients who subsequently failed DRV. In addition, the number of PR mutations increased at failure. The increase in the mean number of mutations was completely related to mutations considered to be associated with DRV resistance following the indications of the main DRV clinical trials. Discussion The higher statistical difference at baseline between failing versus non-failing patients was observed for the V32I and I84V mutations. At DRV failure, the major increase was still observed for V32I; I54L, V11I, T74P and I50V also increased. Despite the increment in the mean number of mutations per patient between baseline and failure, in 21 patients (17.8%) at baseline and 36 (30.5%) at failure, no PR mutation was detected. Conclusion: The HIV-DB interpretation algorithm identified few patients with full DRV resistance at baseline and few patients developed full resistance at DRV failure, indicating that complete resistance to DRV is uncommon. © Springer-Verlag 2011.

Published
2012

9. No pol mutation is associated independently with the lack of immune recovery in patients infected with HIV and failing antiretroviral therapy

Author

Gianotti, N1, Galli, L, Zazzi, M, Ghisetti, V, Bonora, S, Micheli, V, Meraviglia, P, Corsi, P, Bruzzone, B, Menzo, S, Di Giambenedetto, S, De Luca, A, Filice, G, Penco, G, Castagna, A, Collaborators Giacometti A, ARCA database i. n. i. t. i. a. t. i. v. e., Butini, L, del Gobbo, R, Tacconi, D, Corbelli, G, Zanussi, S, Monno, L, Punzi, G, Maggiolo, F, Callegaro, A, Calza, L, Re, Mc, Pristerà, R, Turconi, P, Mandas, A, Tini, S, Carnevale, G, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Di Pietro, M, Bartalesi, F, Colao, G, Tosti, A, Di Biagio, A, Setti, M, Trezzi, M, Orani, A, Pardelli, R, De Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, Gianotti, N, Cicconi, P, Rusconi, S, Gismondo, Mr, Biondi, Ml, Capetti, A, Boeri, E, Pecorari, M, Mussini, C, Santirocchi, M, Brustia, D, Ravanini, P, Dal Bello, F, Romano, N, Mancuso, S, Calzetti, C, Maserati, R, Baldanti, F, Francisci, D, Parruti, G, Polilli, E, Sacchini, D, Martinelli, C, Consolini, R, Vatteroni, L, Vivarelli, A, Nerli, A, Lenzi, L, Magnani, G, Ortolani, P, Andreoni, M, Palamara, G, Fimiani, C, Palmisano, L, Antinori, A, Vullo, Vincenzo, Turriziani, O, Perno, Cf, Montano, M, Cenderello, G, Gonnelli, A, Romano, L, Palumbo, M, Delle Foglie, P, Rossi, C, Poletti, F, Mondino, V, Malena, M, Lattuada, E., Gianotti, N, Galli, L, Zazzi, M, Ghisetti, V, Bonora, S, Micheli, V, Meraviglia, P, Corsi, P, Bruzzone, B, Menzo, S, Di Giambenedetto, S, De Luca, A, Filice, G, Penco, G, Castagna, A, Mancuso, S, Gianotti N, Galli L, Zazzi M, Ghisetti V, Bonora S, Micheli V, Meraviglia P, Corsi P, Bruzzone B, Menzo S, Di Giambenedetto S, De Luca A, Filice G, Penco G, Castagna A, Giacometti A, Butini L, del Gobbo R, Tacconi D, Corbelli G, Zanussi S, Monno L, Punzi G, Maggiolo F, Callegaro A, Calza L, Re MC, Pristerà R, Turconi P, Mandas A, Tini S, Carnevale G, Paolini E, Amadio G, Sighinolfi L, Zuccati G, Morfini M, Manetti R, Di Pietro M, Bartalesi F, Colao G, Tosti A, Di Biagio A, Setti M, Trezzi M, Orani A, Pardelli R, De Gennaro M, Chiodera A, Scalzini A, Palvarini L, Almi P, Todaro G, Cicconi P, Rusconi S, Gismondo MR, Biondi ML, Capetti A, Boeri E, Pecorari M, Mussini C, Santirocchi M, Brustia D, Ravanini P, Dal Bello F, Romano N, Mancuso S, Calzetti C, Maserati R, Baldanti F, Francisci D, Parruti G, Polilli E, Sacchini D, Martinelli C, Consolini R, Vatteroni L, Vivarelli A, Nerli A, Lenzi L, Magnani G, Ortolani P, Andreoni M, Palamara G, Fimiani C, Palmisano L, Antinori A, Vullo V, Turriziani O, Perno CF, Montano M, Cenderello G, Gonnelli A, Romano L, Palumbo M, Delle Foglie P, Rossi C, Poletti F, Mondino V, Malena M, Lattuada E., Gianotti, Nicola, Galli, Laura, Zazzi, Maurizio, Ghisetti, Valeria, Bonora, Stefano, Micheli, Valeria, Meraviglia, Paola, Corsi, Paola, Bruzzone, Bianca, Menzo, Stefano, Di Giambenedetto, Simona, De Luca, Andrea, Filice, Gaetano, Penco, Giovanni, and Castagna, Antonella

Subjects
Male, HIV Infections, Drug resistance, Logistic regression, Resistance to nucleoside reverse transcriptase inhibitor, CD4+ T-lymphocyte, Retrospective Studie, Immunopathology, Antiretroviral Therapy, Highly Active, Resistance to non-nucleoside reverse transcriptase inhibitor, genetics, Resistance to protease inhibitor, HIV Infection, resistance to nucleoside reverse transcriptase inhibitors, Viral, Sida, resistance to protease inhibitors, biology, Reverse-transcriptase inhibitor, Viral Load, Genes, pol, drug therapy/immunology/virology, Reverse Transcriptase Inhibitor, Infectious Diseases, Treatment Outcome, resistance to non-nucleoside reverse transcriptase inhibitors, Reverse Transcriptase Inhibitors, Female, Viral load, medicine.drug, Human, pol, Anti-HIV Agents, Antiretroviral Therapy, Viremia, Infectious Disease, Settore MED/17 - MALATTIE INFETTIVE, pharmacology/therapeutic use, Acquired immunodeficiency syndrome (AIDS), Virology, Drug Resistance, Viral, medicine, Humans, Highly Active, Retrospective Studies, pharmacology/therapeutic use, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Drug Resistance, genetics, Female, Genes, pol, HIV Infections, drug therapy/immunology/virology, HIV-1, drug effects/enzymology/genetics, Humans, Male, Mutation, Retrospective Studies, Reverse Transcriptase Inhibitors, therapeutic use, Treatment Outcome, Viral Load, drug resistance, Anti-HIV Agent, biology.organism_classification, medicine.disease, CD4 Lymphocyte Count, Genes, drug effects/enzymology/genetics, therapeutic use, Mutation, CD4+ T-lymphocytes, HIV-1
Abstract

An investigation was undertaken to determine whether specific pol mutations hinder long-term immune recovery regardless of virological response. In total, 826 patients with >50 HIV RNA copies/ml, who underwent genotypic resistance testing between 1 January 2000 and 31 December 2003 after >3 years of antiretroviral treatment, and were followed up for >3 years after genotypic resistance testing, were analyzed retrospectively. The outcome of the study was the lack of immune recovery after >3 years of follow-up, defined as a slope by linear regression 50 copies/ml divided by the number of HIV RNA measurements during follow-up. Logistic regression was used for univariable and multivariable analysis. Median (Q1, Q3) values at baseline were the following: age 40 (37, 45) years, years on antiretroviral therapy 4.45 (3.65, 5.47), HIV RNA 3.91 (3.39, 4.53) log 10 copies/ml, CD4+ T-cell 358 (211, 524)/μl. After 3.13 years of follow-up, 375 patients (45.4%) showed a lack of immune recovery. The risk of lack of immune recovery increased independently with increasing baseline CD4+ counts (OR=1.104 per 50-cell increase, 95% CI=1.069-1.142, P

Published
2011

10. A novel methodology for large-scale phylogeny partition

Author

Prosperi, Mattia C. F., Ciccozzi, Massimo, Fanti, Iuri, Saladini, Francesco, Pecorari, Monica, Borghi, Vanni, Di Giambenedetto, Simona, Bruzzone, Bianca, Capetti, Amedeo, Vivarelli, Angela, Rusconi, Stefano, Maria Carla, Re, Gismondo, Maria Rita, Sighinolfi, Laura, Gray, Rebecca R., Salemi, Marco, Zazzi, Maurizio, De Luca, Andrea, Giacometti, A, Butini, L, Menzo, S, Tacconi, D, Corbelli, G, Zanussi, S, Monno, L, Punzi, G, Maggiolo, F, Callegaro, A, Calza, L, Re, Mc, Pristerà, R, Turconi, P, Mandas, A, Tini, S, Zoncada, A, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Corsi, P, Galli, L, Di Pietro, M, Bartalesi, F, Colao, G, Tosti, A, Di Biagio, A, Setti, M, Bruzzone, B, Penco, G, Trezzi, M, Orani, A, Pardelli, R, De Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, Cicconi, P, Rusconi, S, Gismondo, Mr, Micheli, V, Biondi, Ml, Gianotti, N, Capetti, A, Meraviglia, P, Boeri, E, Mussini, C, Pecorari, M, Soria, A, Vecchi, L, Santirocchi, M, Brustia, D, Ravanini, P, Dal Bello, F, Romano, N, Mancuso, S, Calzetti, C, Maserati, R, Filice, G, Baldanti, F, Francisci, D, Parruti, G, Polilli, E, Sacchini, D, Martinelli, C, Consolini, R, Vatteroni, L, Vivarelli, A, Dionisio, D, Nerli, A, Lenzi, L, Magnani, G, Ortolani, P, Andreoni, M, Palamara, G, Fimiani, C, Palmisano, L, De Luca, A, Fadda, G, Vullo, Vincenzo, Turriziani, Ombretta, Montano, M, Cenderello, G, Gonnelli, A, Palumbo, M, Ghisetti, V, Bonora, S, Delle Foglie, P, Rossi, C, Grossi, P, Seminari, E, Poletti, F, Mondino, V, Malena, M, Lattuada, E., Prosperi MC, Ciccozzi M, Fanti I, Saladini F, Pecorari M, Borghi V, Di Giambenedetto S, Bruzzone B, Capetti A, Vivarelli A, Rusconi S, Re MC, Gismondo MR, Sighinolfi L, Gray RR, Salemi M, Zazzi M, De Luca A, ARCA collaborative group., Prosperi, M, Ciccozzi, M, Fanti, I, Saladini, F, Pecorari, M, Borghi, V, Di Giambenedetto, S, Bruzzone, B, Capetti, A, Vivarelli, A, Rusconi, S, Re, M, Gismondo, M, Sighinolfi, L, Gray, R, Salemi, M, Zazzi, M, De Luca, A, and Mancuso, S

Subjects
Genetics and Molecular Biology (all), Male, pol, Theoretical computer science, Inference, Gene Products, pol, General Physics and Astronomy, HIV Infections, Biology, Network topology, Settore MED/17 - MALATTIE INFETTIVE, Biochemistry, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Physics and Astronomy (all), 0302 clinical medicine, Search algorithm, phylogenetic analysis, virus transmission, Gene Products, Humans, HIV Infection, 030212 general & internal medicine, Phylogeny, 030304 developmental biology, Algorithms, Classification, Female, HIV-1, Biochemistry, Genetics and Molecular Biology (all), Chemistry (all), Genetics, 0303 health sciences, Multidisciplinary, Phylogenetic tree, Node (networking), HIV, General Chemistry, Partition (database), Algorithm, Identification (information), Transmission (telecommunications), METHODOLOGY, Human
Abstract

Understanding the determinants of virus transmission is a fundamental step for effective design of screening and intervention strategies to control viral epidemics. Phylogenetic analysis can be a valid approach for the identification of transmission chains, and very-large data sets can be analysed through parallel computation. Here we propose and validate a new methodology for the partition of large-scale phylogenies and the inference of transmission clusters. This approach, on the basis of a depth-first search algorithm, conjugates the evaluation of node reliability, tree topology and patristic distance analysis. The method has been applied to identify transmission clusters of a phylogeny of 11,541 human immunodeficiency virus-1 subtype B pol gene sequences from a large Italian cohort. Molecular transmission chains were characterized by means of different clinical/demographic factors, such as the interaction between male homosexuals and male heterosexuals. Our method takes an advantage of a flexible notion of transmission cluster and can become a general framework to analyse other epidemics. © 2011 Macmillan Publishers Limited. All rights reserved.

Published
2011
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11. Detection of drug resistance mutations at low plasma HIV-1 RNA load in a European multicentre cohort study

Author

Prosperi, Mc1, Mackie, N, Di Giambenedetto, S, Zazzi, M, Camacho, R, Fanti, I, Torti, C, Sönnerborg, A, Kaiser, R, Codoñer, Fm, Van Laethem, K, Bansi, L, van de Vijver DA, Geretti, Am, De Luca, A, Giacometti A, SEHERE c. o. n. s. o. r. t. i. u. m., Butini, L, del Gobbo, R, Menzo, S, Tacconi, D, Corbelli, G, Zanussi, S, Monno, L, Punzi, G, Maggiolo, F, Callegaro, A, Calza, L, Carla Re, M, Pristerà, R, Turconi, P, Mandas, A, Tini, S, Zoncada, A, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Corsi, P, Galli, L, Di Pietro, M, Bartalesi, F, Colao, G, Tosti, A, Di Biagio, A, Setti, M, Bruzzone, B, Penco, G, Trezzi, M, Orani, A, Pardelli, R, De Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, d'Arminio Monforte, A, Cicconi, P, Rusconi, S, Gismondo, Mr, Micheli, V, Biondi, Ml, Gianotti, N, Capetti, A, Meraviglia, P, Boeri, E, Mussini, C, Pecorari, M, Soria, A, Vecchi, L, Santirocchi, M, Brustia, D, Ravanini, P, Bello, Fd, Romano, N, Mancuso, S, Calzetti, C, Maserati, R, Filice, G, Baldanti, F, Francisci, D, Parruti, G, Polilli, E, Sacchini, D, Martinelli, C, Consolini, R, Vatteroni, L, Vivarelli, A, Dionisio, D, Nerli, A, Lenzi, L, Magnani, G, Ortolani, P, Andreoni, M, Palamara, G, Fimiani, C, Palmisano, L, Fadda, G, Vullo, Vincenzo, Turriziani, O, Montano, M, Cenderello, G, Gonnelli, A, Palumbo, M, Ghisetti, V, Bonora, S, Foglie, Pd, Rossi, C, Grossi, P, Seminari, E, Poletti, F, Mondino, V, Malena, M, Lattuada, E, Lengauer, T, Däumer, M, Hoffmann, D, Schülter, E, Müller, C, Oette, M, Reuter, S, Esser, S, Fätkenheuer, G, Rockstroh, J, Incardona, F, Rosen Zvi, M, Clotet, B, Thalme, A, Svedhem, V, Bratt, G, Gargiulo, F, Lapadula, G, Manca, N, Paraninfo, G, Quiros Roldan, E, Carosi, G, Castelnuovo, F, Vandamme, Am, Van Wijngaerden, E, Ainsworth, J, Anderson, J, Babiker, A, Dunn, D, Easterbrook, P, Fisher, M, Gazzard, B, Garrett, N, Gilson, R, Gompels, M, Hill, T, Johnson, M, Leen, C, Orkin, C, Phillips, A, Pillay, D, Porter, K, Post, F, Sabin, C, Sadiq, T, Schwenk, A, Walsh, J, Delpech, V, Palfreeman, A, Glabay, A, Lynch, J, Hand, J, de Souza, C, Perry, N, Tilbury, S, Churchill, D, Nelson, M, Waxman, M, Mandalia, S, Kall, M, Korat, H, Taylor, C, Ibrahim, F, Campbell, L, James, L, Brima, N, Williams, I, Youle, M, Lampe, F, Smith, C, Grabowska, H, Chaloner, C, Puradiredja, Di, Weber, J, Ramzan, F, Carder, M, Wilson, A, Dooley, D, Asboe, D, Pozniak, A, Cameron, S, Cane, P, Chadwick, D, Clark, D, Collins, S, Lazarus, L, Dolling, D, Fearnhill, E, Castro, H, Coughlin, K, Zuckerman, M, Booth, C, Goldberg, D, Hale, A, Kaye, S, Kellam, P, Leigh Brown, A, Smit, E, Templeton, K, Tilston, P, Tong, W, Zhang, H, Ushiro Lumb, I, Oliver, T, Bibby, D, Mitchell, S, Mbisa, T, Wildfire, A, Tandy, R, Shepherd, J, Maclean, A, Bennett, D, Hopkins, M, Garcia Diaz, A, Kirk, S, Sloot, P. M., Virology, Prosperi, M, Mackie, N, di Giambenedetto, S, Zazzi, M, Camacho, R, Fanti, I, Torti, C, Sönnerborg, A, Kaiser, R, Codoñer, F, van laethem, K, Bansi, L, van de Vijver, D, Geretti, A, de luca, A, and Mancuso, S

Subjects
Male, Drug Resistance, HIV Infections, Drug resistance, Cohort Studies, 0302 clinical medicine, Genotype, HIV Infection, Pharmacology (medical), 030212 general & internal medicine, Viral, 0303 health sciences, Proteolytic enzymes, Genotypic testing, HIV, Viral load, Adult, Anti-HIV Agents, CD4 Lymphocyte Count, Europe, Female, HIV-1, Humans, RNA, Viral, Viral Proteins, Drug Resistance, Viral, Mutation, Missense, Viral Load, Pharmacology, Infectious Diseases, 3. Good health, Cohort, Cohort study, Human, Microbiology (medical), Biology, Settore MED/17 - MALATTIE INFETTIVE, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Viral Protein, 030306 microbiology, Anti-HIV Agent, Virology, Reverse transcriptase, Regimen, genotypic testing, viral load, Immunology, Mutation, RNA, Missense, Cohort Studie
Abstract

Background and objectives: Guidelines indicate a plasma HIV-1 RNA load of 500-1000 copies/mL as the minimal threshold for antiretroviral drug resistance testing. Resistance testing at lower viral load levels may be useful to guide timely treatment switches, although data on the clinical utility of this remain limited. We report here the influence of viral load levels on the probability of detecting drug resistance mutations (DRMs) and other mutations by routine genotypic testing in a large multicentre European cohort, with a focus on tests performed at a viral load

Published
2011

12. Low Rate of Virological Failure and Maintenance of Susceptibility to HIV-1 Protease Inhibitors with First-Line Lopinavir/Ritonavir-Based Antiretroviral Treatment in Clinical Practice

Author

Prosperi, Mc, Zazzi, M, Punzi, G, Monno, L, Colao, G, Corsi, P, Di Giambenedetto, S, Meini, G, Ghisetti, V, Bonora, S, Pecorari, M, Gismondo, Mr, Bagnarelli, P, Carli, T, De Luca, A, ARCA Collaborative Group, Giacometti, A, Butini, L, del Gobbo, R, Menzo, S, Tacconi, D, Corbelli, G, Zanussi, S, Maggiolo, F, Callegaro, A, Calza, L, Re, Mc, Raffaele, P, Turconi, P, Mandas, A, Tini, S, Zoncada, A, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Galli, L, Di Pietro, M, Bartalesi, F, Tosti, A, Di Biagio, A, Setti, M, Bruzzone, B, Penco, G, Trezzi, M, Orani, A, Pardelli, R, De Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, Monforte, A, Cicconi, P, Rusconi, S, Micheli, V, Biondi, Ml, Gianotti, N, Capetti, A, Meraviglia, P, Boeri, E, Mussini, C, Soria, A, Vecchi, L, Santirocchi, M, Brustia, D, Ravanini, P, Dal Bello, F, Romano, N, Mancuso, S, Calzetti, C, Maserati, R, Filice, G, Baldanti, F, Francisci, D, Parruti, G, Polilli, E, Sacchini, D, Martinelli, C, Consolini, Rita, Clinic of Infectious Diseases, Università cattolica del Sacro Cuore [Roma] (Unicatt), Molecular Biology, Microbiology and Virology, Bari University Hospital, Clinical Infectious Diseases, Careggi University Hospital, Unit of Infectious Diseases, Catholic Universisty of Sacred Heart, A. Savoia Hospital, infectiuos diseases, Università degli studi di Torino (UNITO), Modena University Hospital, L. Sacco University Hospital, Ancona University Hospital, Grosseto General Hospital, Institute of Infectious Diseases, Sacro Cuore Catholic University, Infectious Diseases Unit, University Hospital of Siena, Prosperi, M, Zazzi, M, Punzi, G, Monno, L, Colao, G, Corsi, P, Di Giambenedetto, S, Meini, G, Ghisetti, V, Bonora, S, Pecorari, M, Gismondo, M, Bagnarelli, P, Carli, T, De Luca, A, Mancuso, S, Prosperi MC, Zazzi M, Punzi G, Monno L, Colao G, Corsi P, Di Giambenedetto S, Meini G, Ghisetti V, Bonora S, Pecorari M, Gismondo MR, Bagnarelli P, Carli T, De Luca A, ARCA Collaborative Group [.., Giacometti A, Butini L, del Gobbo R, Menzo S, Tacconi D, Corbelli G, Zanussi S, Maggiolo F, Callegaro A, Calza L, Re MC, Raffaele P, Turconi P, Mandas A, Tini S, Zoncada A, Paolini E, Amadio G, Sighinolfi L, and ]

Subjects
Male, Lopinavir/ritonavir, HIV Infections, boosted protease inhibitor, Lopinavir, Cohort Studies, 0302 clinical medicine, Antiretroviral Therapy, Highly Active, virologic failure, HIV Infection, Treatment Failure, 030212 general & internal medicine, Pyrimidinone, 0303 health sciences, education.field_of_study, lopinavir/ritonavir, Viral Load, Resistance mutation, first-line antiretroviral therapy, Reverse Transcriptase Inhibitor, 3. Good health, Treatment Outcome, Infectious Diseases, RNA, Viral, Reverse Transcriptase Inhibitors, Medicine, Drug Therapy, Combination, Female, Survival Analysi, Viral load, Human, medicine.drug, Anti-HIV Agents, Population, Pyrimidinones, Settore MED/17 - MALATTIE INFETTIVE, Emtricitabine, human immunodeficiency virus type 1, 03 medical and health sciences, Virology, Drug Resistance, Viral, antiretroviral drug resistance, medicine, Humans, Protease inhibitor (pharmacology), education, HIV Protease Inhibitor, Ritonavir, 030306 microbiology, business.industry, Anti-HIV Agent, HIV Protease Inhibitors, Survival Analysis, HIV-1, Cohort Studie, business
Abstract

Protease inhibitor (PI)-resistant HIV-1 has hardly ever been detected at failed boosted PI-based first-line antiretroviral regimens in clinical trials. However, this phenomenon has not been investigated in clinical practice. To address this gap, data from patients starting a first-line lopinavir/ritonavir (LPV/rtv)-based therapy with available baseline HIV-1 RNA load, a viral genotype and follow-up viral load after 3 and 6 months of treatment were extracted from the Italian Antiretroviral Resistance Cohort Analysis (ARCA) observational database. Based on survival analysis, 39 (7.1%) and 43 (7.8%) of the 548 examined patient cases had an HIV-1 RNA >500 and >50 copies/ml, respectively, after 6 months of treatment. Cox proportional hazard models detected baseline HIV-1 RNA (RH 1.79, 95%CI 1.10-2.92 per 1 - log10 increase, P = 0.02) and resistance to the nucleoside backbone (RH 1.04, 95%CI 1.02-1.06 per 10-point increase using the Stanford HIVdb algorithm, P < 0.001) as independent predictors of HIV-1 RNA at >500 copies/ml, but not at the >50 copies/ml cutoff criteria. Higher baseline viral load, older patient age, heterosexual route of infection and use of tenofovir/emtricitabine were predictors of failure at month 3 using the 50-copy and/or 500-copy threshold. Resistance to LPV/rtv did not occur or increase in any of the available 36 follow-up HIV-1 genotypes. Resistance to the nucleoside backbone (M184V) developed in four cases. Despite the likely differences in patient population and adherence, both the low rate of virological failure and the lack of development of LPV/rtv resistance documented in clinical trials are thus confirmed in clinical practice. J. Med. Virol. 82:1996-2003, 2010. © 2010 Wiley-Liss, Inc.

Published
2010
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13. Low rate of virological failure and maintenance of susceptibility to HIV-1 protease inhibitors with first-line lopinavir/ritonavir-based antiretroviral treatment in clinical practice

Author

Prosperi, Mc1, Zazzi, M, Punzi, G, Monno, L, Colao, G, Corsi, P, Di Giambenedetto, S, Meini, G, Ghisetti, V, Bonora, S, Pecorari, M, Gismondo, Mr, Bagnarelli, P, Carli, T, De Luca, A, Collaborators Giacometti A, ARCA Collaborative G. r. o. u. p., Butini, L, del Gobbo, R, Menzo, S, Tacconi, D, Corbelli, G, Zanussi, S, Maggiolo, F, Callegaro, A, Calza, L, Re, Mc, Raffaele, P, Turconi, P, Mandas, A, Tini, S, Zoncada, A, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Galli, L, Di Pietro, M, Bartalesi, F, Tosti, A, Di Biagio, A, Setti, M, Bruzzone, B, Penco, G, Trezzi, M, Orani, A, Pardelli, R, De Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, Monforte, Ad, Cicconi, P, Rusconi, S, Micheli, V, Biondi, Ml, Gianotti, N, Capetti, A, Meraviglia, P, Boeri, E, Mussini, C, Soria, A, Vecchi, L, Santirocchi, M, Brustia, D, Ravanini, P, Dal Bello, F, Romano, N, Mancuso, S, Calzetti, C, Maserati, R, Filice, G, Baldanti, F, Francisci, D, Parruti, G, Polilli, E, Sacchini, D, Martinelli, C, Consolini, R, Vatteroni, L, Vivarelli, A, Dionisio, D, Nerli, A, Lenzi, L, Magnani, G, Ortolani, P, Andreoni, M, Palamara, G, Fimiani, C, Palmisano, L, Vullo, Vincenzo, Turriziani, O, Montano, M, Cenderello, G, Gonnelli, A, Palumbo, M, Delle Foglie, P, Rossi, C, Poletti, F, Mondino, V, Malena, M, and Lattuada, E.

Published
2010

14. Rules-based HIV-1 genotypic resistance interpretation systems predict 8 week and 24 week virological antiretroviral treatment outcome and benefit from drug potency weighting

Author

Zazzi, M, Prosperi, M, Vicenti, I, Di Giambenedetto, S, Callegaro, A, Bruzzone, B, Baldanti, F, Gonnelli, A, Boeri, E, Paolini, E, Rusconi, S, Giacometti, A, Maggiolo, F, Menzo, S, De Luca, A, ARCA Collaborative Group, Butini, L, del Gobbo, R, Tacconi, D, Corbelli, G, Zanussi, S, Monno, L, Punzi, G, Calza, L, Re, Mc, Pristerà, R, Turconi, P, Mandas, A, Tini, S, Carnevale, G, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Corsi, P, Galli, L, Di Pietro, M, Bartalesi, F, Colao, G, Tosti, A, Di Biagio, A, Setti, M, Penco, G, Trezzi, M, Orani, A, Pardelli, R, De Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, Cicconi, P, Gismondo, Mr, Micheli, V, Biondi, Ml, Gianotti, N, Capetti, A, Meraviglia, P, Mussini, C, Pecorari, M, Santirocchi, M, Brustia, D, Ravanini, P, Dal Bello, F, Romano, N, Mancuso, S, Calzetti, C, Maserati, R, Filice, G, Francisci, D, Parruti, G, Polilli, E, Sacchini, D, Martinelli, C, Consolini, Rita, Zazzi, M, Prosperi, M, Vicenti, I, Di Giambenedetto, S, Callegaro, A, Bruzzone, B, Baldanti, F, Gonnelli, A, Boeri, E, Paolini, E, Rusconi, S, Giacometti, A, Maggiolo, F, Menzo, S, De Luca, A, Mancuso, S, Zazzi M, Prosperi M, Vicenti I, Di Giambenedetto S, Callegaro A, Bruzzone B, Baldanti F, Gonnelli A, Boeri E, Paolini E, Rusconi S, Giacometti A, Maggiolo F, Menzo S, De Luca A, ARCA Collaborative Group: [.., Butini L, del Gobbo R, Tacconi D, Corbelli G, Zanussi S, Monno L, Punzi G, Calza L, Re M C, Pristerà R, Turconi P, Mandas A, Tini S, and ]

Subjects
Male, interpretation system, HIV Infections, Drug resistance, Logistic regression, Retrospective Studie, HIV Infection, Pharmacology (medical), Microbial Sensitivity Test, Middle Aged, Prognosis, genotype, drug resistance, algorithm, Algorithm, Treatment Outcome, Infectious Diseases, Italy, RNA, Viral, Female, Cohort study, Human, Microbiology (medical), Adult, medicine.medical_specialty, Genotype, Logistic Model, Anti-HIV Agents, Prognosi, antiretroviral, Microbial Sensitivity Tests, Internal medicine, medicine, Potency, Animals, Humans, Retrospective Studies, Pharmacology, Receiver operating characteristic, business.industry, Animal, Anti-HIV Agent, Retrospective cohort study, Odds ratio, genotype, drug potency weighting, Weighting, Logistic Models, ROC Curve, Immunology, HIV-1, business
Abstract

Objectives: To test retrospectively the ability of four freely available rules-based expert systems to predict short- and medium-term virological outcome following an antiretroviral treatment switch in pre-treated HIV-1 patients. Methods: The HIV-1 genotype interpretation systems (GISs) HIVdb, ANRS, Rega and AntiRetroScan were tested for their accuracy in predicting response to highly active antiretroviral therapy using 8 week (n = 765) and 24 week (n = 634) follow-up standardized treatment change episodes extracted from the Italian Antiretroviral Resistance Cohort Analysis (ARCA) database. A genotypic sensitivity score (GSS) was derived for each genotype-treatment pair for the different GISs and tested as a predictor of virological treatment outcome by univariable and multivariable logistic regression as well as by receiver operating characteristic curve analysis. The two systems implementing drug potency weights (AntiRetroScan and Rega) were evaluated with and without this correction factor. Results: All four GSSs were strong predictors of virological treatment outcome at both 8 and 24 weeks after adjusting for baseline viro-immunological parameters and previous drug exposure (odds ratios ranging from 2.04 to 2.43 per 1 unit GSS increase; P < 0.001 for all the systems). The accuracy of AntiRetroScan and Rega was significantly increased by drug potency weighting with respect to the unweighted versions (P ≤ 0.001). HIVdb and ANRS also increased their performance with the same drug potency weighting adopted by AntiRetroScan and Rega, respectively (P < 0.001 for both analyses). Conclusions: Currently available GISs are valuable tools for assisting antiretroviral treatment choices. Drug potency weighting can increase the accuracy of all systems. © The Author 2009. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

Published
2009

16. A Prognostic Model for Estimating the Time to Virologic Failure in HIV-1 Infected Patients Undergoing a New Combination Antiretroviral Therapy Regimen

Author

PProsperi MC, Di Giambenedetto S, Fanti I, Meini G, Bruzzone B, Callegaro A, Penco G, Bagnarelli P, Micheli V, Paolini E, Di Biagio A, Ghisetti V, Di Pietro M, Zazzi M, De Luca A, Giacometti A, Butini L, del Gobbo R, Menzo S, Tacconi D, Corbelli G, Zanussi S, Monno L, Punzi G, Maggiolo F, CALZA, LEONARDO, RE, MARIA CARLA, Pristerà R, Turconi P, Mandas A, Tini S, Carnevale G, Amadio G, Sighinolfi L, Zuccati G, Morfini M, Manetti R, Galli L, Bartalesi F, Colao G, Tosti A, Setti M, Trezzi M, Orani A, Pardelli R, De Gennaro M, Chiodera A, Scalzini A, Palvarini L, Almi P, Todaro G, Gianotti N, Cicconi P, Rusconi S, Gismondo MR, Biondi ML, Capetti A, Meraviglia P, Boeri E, Pecorari M, Mussini C, Santirocchi M, Brustia D, Ravanini P, Dal Bello F, Romano N, Mancuso S, Calzetti C, Maserati R, Baldanti F, Francisci D, Parruti G, Polilli E, Sacchini D, Martinelli C, Consolini R, Vatteroni L, Vivarelli A, Nerli A, Lenzi L, Magnani G, Ortolani P, Andreoni M, Palamara G, Fimiani C, Palmisano L, Antinori A, Vullo V, Turriziani O, Perno CF, Montano M, Cenderello G, Gonnelli A, Romano L, Palumbo M, Bonora S, Delle Foglie P, Rossi C, Poletti F, Mondino V, Malena M, Lattuada E., PProsperi MC, Di Giambenedetto S, Fanti I, Meini G, Bruzzone B, Callegaro A, Penco G, Bagnarelli P, Micheli V, Paolini E, Di Biagio A, Ghisetti V, Di Pietro M, Zazzi M, De Luca A, Giacometti A, Butini L, del Gobbo R, Menzo S, Tacconi D, Corbelli G, Zanussi S, Monno L, Punzi G, Maggiolo F, Calza L, Re MC, Pristerà R, Turconi P, Mandas A, Tini S, Carnevale G, Amadio G, Sighinolfi L, Zuccati G, Morfini M, Manetti R, Galli L, Bartalesi F, Colao G, Tosti A, Setti M, Trezzi M, Orani A, Pardelli R, De Gennaro M, Chiodera A, Scalzini A, Palvarini L, Almi P, Todaro G, Gianotti N, Cicconi P, Rusconi S, Gismondo MR, Biondi ML, Capetti A, Meraviglia P, Boeri E, Pecorari M, Mussini C, Santirocchi M, Brustia D, Ravanini P, Dal Bello F, Romano N, Mancuso S, Calzetti C, Maserati R, Baldanti F, Francisci D, Parruti G, Polilli E, Sacchini D, Martinelli C, Consolini R, Vatteroni L, Vivarelli A, Nerli A, Lenzi L, Magnani G, Ortolani P, Andreoni M, Palamara G, Fimiani C, Palmisano L, Antinori A, Vullo V, Turriziani O, Perno CF, Montano M, Cenderello G, Gonnelli A, Romano L, Palumbo M, Bonora S, Delle Foglie P, Rossi C, Poletti F, Mondino V, Malena M, Lattuada E., Prosperi, M, Di Giambenedetto, S, Fanti, I, Meini, G, Bruzzone, B, Callegaro, A, Penco, G, Bagnarelli, P, Micheli, V, Paolini, E, Di Biagio, A, Ghisetti, V, Di Pietro, M, Zazzi, M, De Luca, A, and Mancuso, S

Subjects
Oncology, Male, Adult, Anti-HIV Agents, Cohort Studies, Drug Therapy, Combination, Female, HIV Infections, HIV-1, Humans, Middle Aged, Proportional Hazards Models, Treatment Failure, Viral Load, 0302 clinical medicine, ANTIRETROVIRAL THERAPY, Medicine, HIV Infection, 030212 general & internal medicine, 0303 health sciences, Health Policy, 3. Good health, Computer Science Applications, Censoring (clinical trials), Cohort, Combination, lcsh:R858-859.7, Viral load, Human, Research Article, Cart, medicine.medical_specialty, antiretroviral therapy, Health Informatics, Settore MED/17 - MALATTIE INFETTIVE, lcsh:Computer applications to medicine. Medical informatics, 03 medical and health sciences, Drug Therapy, Internal medicine, Survival analysis, 030306 microbiology, business.industry, Proportional hazards model, ANTIRETROVIRAL DRUGS, Anti-HIV Agent, HIV, GENOTYPES, Discontinuation, Regimen, Immunology, Proportional Hazards Model, Cohort Studie, business
Abstract

Background HIV-1 genotypic susceptibility scores (GSSs) were proven to be significant prognostic factors of fixed time-point virologic outcomes after combination antiretroviral therapy (cART) switch/initiation. However, their relative-hazard for the time to virologic failure has not been thoroughly investigated, and an expert system that is able to predict how long a new cART regimen will remain effective has never been designed. Methods We analyzed patients of the Italian ARCA cohort starting a new cART from 1999 onwards either after virologic failure or as treatment-naïve. The time to virologic failure was the endpoint, from the 90th day after treatment start, defined as the first HIV-1 RNA > 400 copies/ml, censoring at last available HIV-1 RNA before treatment discontinuation. We assessed the relative hazard/importance of GSSs according to distinct interpretation systems (Rega, ANRS and HIVdb) and other covariates by means of Cox regression and random survival forests (RSF). Prediction models were validated via the bootstrap and c-index measure. Results The dataset included 2337 regimens from 2182 patients, of which 733 were previously treatment-naïve. We observed 1067 virologic failures over 2820 persons-years. Multivariable analysis revealed that low GSSs of cART were independently associated with the hazard of a virologic failure, along with several other covariates. Evaluation of predictive performance yielded a modest ability of the Cox regression to predict the virologic endpoint (c-index≈0.70), while RSF showed a better performance (c-index≈0.73, p < 0.0001 vs. Cox regression). Variable importance according to RSF was concordant with the Cox hazards. Conclusions GSSs of cART and several other covariates were investigated using linear and non-linear survival analysis. RSF models are a promising approach for the development of a reliable system that predicts time to virologic failure better than Cox regression. Such models might represent a significant improvement over the current methods for monitoring and optimization of cART.

Published
2011
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19. New advances on human TH1 and TH2 cells

Author

Romagnani, S., Decarli, M., Piccinni, M. P., Manetti, R., Parronchi, P., D'Elios, M. M., Annunziato, F., Sampognaro, S., Giudizi, M. G., Biagiotti, R., Almerigogna, F., Maggi, E., and Delprete, G. F.

Published
1994

26. CD30 expression by CD8+ T cells producing type 2 helper cytokines. Evidence for large numbers of CD8+CD30+ T cell clones in human immunodeficiency virus infection.

Author

Manetti, R, primary, Annunziato, F, additional, Biagiotti, R, additional, Giudizi, M G, additional, Piccinni, M P, additional, Giannarini, L, additional, Sampognaro, S, additional, Parronchi, P, additional, Vinante, F, additional, Pizzolo, G, additional, Maggi, E, additional, and Romagnani, S, additional

Published
1994
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30. Interleukin 12 induces stable priming for interferon gamma (IFN-gamma) production during differentiation of human T helper (Th) cells and transient IFN-gamma production in established Th2 cell clones.

Author

Manetti, R, primary, Gerosa, F, additional, Giudizi, M G, additional, Biagiotti, R, additional, Parronchi, P, additional, Piccinni, M P, additional, Sampognaro, S, additional, Maggi, E, additional, Romagnani, S, additional, and Trinchieri, G, additional

Published
1994
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32. CXCR3 and αE137 integrin identify a subset of CD8+ mature thymocytes that share phenotypic and functional properties with CD8+ gut intraepithelial lymphocytes.

Author

Annunziato, F., Cosmi, L., Liotta, F., Lazzeri, E., Romagnani, P., Angeli, R., Lasagni, L., Manetti, R., Marra, F, Gerard, C., Petrai, I., Dello Sbarba, P., Tonelli, F., Maggi, E., and Romagnani, S.

Subjects
T cell receptors, LYMPHOCYTES, GASTROINTESTINAL mucosa, CELL-mediated lympholysis, LYMPH nodes, GASTROINTESTINAL motility, PHENOTYPES
Abstract

Background: We previously demonstrated the existence of two distinct subsets of T cell receptor (TCR)αβ+CD8cαβ+ single positive (SP) cells in human postnatal thymus which express the chemokine receptor CCR7 or CXCR3 and migrate in vitro in response to their specific ligands. Aim: To investigate whether these two CD8+ thymocyte subsets had distinct peripheral colonisation. Methods: TCRαβ+CD8+ SP cells were obtained from normal postnatal thymus, mesenteric lymph node (LNs), small bowel, and peripheral blood (PB) specimens. Cells were then evaluated for expression of surface molecules, cytolytic potential, telomere length, and profile of cytokine production. Results: CD8+CCR7+CXCR3- thymocytes exhibited CD62L, in common with those which localise to LNs. In contrast, CD8+CCR7-CXCR3+ thymocytes lacked CD62L but exhibited CD103, similar to intraepithelial lymphocytes (IELs) present in the gut mucosa where the CXCR3 ligand, CXCL10, and the CD103 ligand, E-cadherin, are highly and consistently expressed. In addition, thymocytes and gut CD8+CXCR3+CD103+ cells showed comparable telomere length, which was higher than that of PB CXCR3+CD8+ T cells. However, both of these populations contained perforin and granzyme A, and displayed the ability to produce interferon γ and interleukin 2. Of note, CXCR3 deficient, in comparison with wild-type C57Black/6, mice showed decreased proportions of CD3+CD8αβ+ and increased proportions of CD3+CD8αα+ lymphocytes at gut level. Moreover, adoptive transfer of CD3+CD8αβ+ thymocytes from wild-type into CXCR3 deficient mice resulted in a significant increase in CD3+CD8αβ+ T cells in the gut mucosa but not in other tissues. Conclusions: The results of this study demonstrate the existence of a previously unrecognised subset of TCRαβ+CD8αβ+ SP CXCR3+CD103+ thymocytes which share phenotypic and functional features with CD8+ IELs, thus suggesting the possibility of their direct colonisation of the gut mucosa. [ABSTRACT FROM AUTHOR]

Published
2006
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36. Low pH activates the vacuolating toxin of Helicobacter pylori, which becomes acid and pepsin resistant.

Author

de Bernard, M, Papini, E, de Filippis, V, Gottardi, E, Telford, J, Manetti, R, Fontana, A, Rappuoli, R, and Montecucco, C

Abstract

The protein toxin VacA, produced by cytotoxic strains of Helicobacter pylori, causes a vacuolar degeneration of cells, which eventually die. VacA is strongly activated by a short exposure to acidic solutions in the pH 1.5-5.5 range, followed by neutralization. Activated VacA has different CD and fluorescence spectra and a limited proteolysis fragmentation pattern from VacA kept at neutral pH. Moreover, activated VacA is resistant to pH 1.5 and to pepsin. The relevance of these findings to pathogenesis of H. pylori-induced gastrointestinal ulcers is discussed.

Published
1995

37. Binding of the Helicobacter pylori vacuolating cytotoxin to target cells.

Author

Massari, P, Manetti, R, Burroni, D, Nuti, S, Norais, N, Rappuoli, R, and Telford, J L

Abstract

The vacuolating cytotoxin of Helicobacter pylori, VacA, enters the cytoplasm of target cells and causes vacuolar degeneration by interfering with late stages of endocytosis. By using indirect immunofluorescence and flow cytometry, we have demonstrated that VacA binds to specific high-affinity cell surface receptors and that this interaction is necessary for cell intoxication.

Published
1998

39. The burden of HIV-Associated neurocognitive disorder (HAND) in post-HAART era: Amultidisciplinary review of the literature

Author

Caruana G, Vidili G, Pa, Serra, Bagella P, Spanu A, Fiore V, Df, Calvisi, Manetti R, Rocchitta G, Susanna Maria F. NUVOLI, Babudieri S, Mm, Simile, and Madeddu G

Subjects
AIDS Dementia Complex, Cost of Illness, Antiretroviral Therapy, Highly Active, Humans
Abstract

The purpose of the present multidisciplinary review is to give an updated insight into the most recent findings regarding the pathophysiology, diagnosis and therapeutics of HIV-associated neurocognitive disorder (HAND).We performed a comprehensive search, through electronic databases (Pubmed - MEDLINE) and search engines (Google Scholar), of peer-reviewed publications (articles and reviews) and conferences proceedings on HAND pathophysiology, diagnosis, and therapy, from 1999 to 2016.It seems to be increasingly clear that neurodegeneration in HIV-1 affected patients is a multi-faceted disease involving numerous factors, from chronic inflammation to central nervous system (CNS) compartmentalization of HIV. Diagnosis of HAND may benefit from both laboratory analysis and advanced specific neuroimaging techniques. As regards HAND therapy, modified HAART combinations and simplification strategies have been tested, while novel exciting frontiers seem to involve the use of nanoparticles with the ability to cross the Blood-Brain Barrier (BBB).Albeit highly active antiretroviral therapy (HAART) allowed a major decrease in morbidity and mortality for AIDS patients, CNS involvement still represents a challenge in HIV patients even today, affecting up to 50% of patients with access to combination antiretroviral therapy (cART). Future studies will have to focus on CNS compartmentalization, drugs' ability to penetrate and suppress viral replication in this compartment, and on new approaches to reduce HIV-associated neuroinflammation.

41. Cytoplasmic nucleoside-triphosphatase similar to axonemal dynein occur widely in different cell types

Author

Pallini, V., Mencarelli, C., LUISA BRACCI, Contorni, M., Ruggiero, P., Tiezzi, A., and Manetti, R.

Subjects
Adenosine Triphosphatases, Brain Chemistry, Cytoplasm, Diptera, Proteins, Nucleoside-Triphosphatase, Phosphoric Monoester Hydrolases, Molecular Weight, Tubulin, Animals, Humans, Cattle, Electrophoresis, Polyacrylamide Gel, Female, Pyrophosphatases, Peptides, Microtubule-Associated Proteins, HeLa Cells, Ovum

42. Underserved populations and bacterial and protozoal sexually transmitted infections: a lost health-care opportunity

Author

Fiore, V., Latte, G., Giordano MADEDDU, Galleri, G., Rocchitta, G., Nuvoli, S., Calvisi, D., Bagella, P., Manetti, R., Serra, P. A., Spanu, A., and Babudieri, S.

Subjects
Male, Transients and Migrants, Databases, Factual, Substance-Related Disorders, Sexual Behavior, Ill-Housed Persons, Sexually Transmitted Diseases, Humans, Female, Delivery of Health Care, Anti-Bacterial Agents
Abstract

The purpose of our review is an update about the burden of sexually transmitted infections (STIs) among various types of underserved populations, such as migrants, substance abusers, homeless and incarcerated inmates. First-line test and treatment based on the latest available evidence according to the revised guidelines of Centers for Disease Control and Prevention have also been considered.We performed a comprehensive research using scientific databases such as Medline and Pubmed, followed by a review of citations and reference list. A consultation with other experts in the management of the various subpopulations was also conducted.Health-care is often influenced by social determinants, which play a vital role in the diffusion of STIs. The consequence is a socio-economical and ethnic disparity in the rate of STIs. Early screening and treatment of STIs should be implemented in clinical practice, starting from marginalized social groups, which are the most affected by this health problem.In the literature, there are very few papers containing information on STIs prevalence in various types of underserved populations, such as migrants, substance abusers, homeless and incarcerated inmates. The availability of more accurate epidemiological data is needed. In these groups, the most relevant barrier is the lower perception of health-care need, with an underestimation of risk and symptoms of STIs, causing a retard of diagnosis and health-care provision and use. For these populations, targeted interventions are needed, particularly on unaware people, responsible for most STIs transmissions.

46. Immune cell impact of three differently coated lipid nanocapsules: pluronic, chitosan and polyethylene glycol

Author

Francesco Sgarrella, Cristiano Farace, Lucia Gemma Delogu, Marco Orecchioni, Juan A. Marchal, J. M. Peula-Garcia, Yolande Asara, Roberto Madeddu, Paola Sánchez-Moreno, Roberto Manetti, [Farace,C, Asara,Y, Madeddu,R] Department of Biomedical Science, University of Sassari, Sassari, Italy. [Sánchez-Moreno,P, Peula-García,JM, Delogu,LG] Biocolloid and Fluid Physics Group, Department of Applied Physics, University of Granada, Granada, Spain. [Orecchioni,M, Manetti,R, Sgarrella,F] Department of Chemistry and Pharmacy University of Sassari, Sassari, Italy. [Peula-García,JM] Department of Applied Physics II, University of Málaga,Málaga, Spain. [Marchal,JA] Biopathology and Medicine Regenerative Institute (IBIMER), University of Granada, Granada, Spain. Biosanitary Institute of Granada (ibs.GRANADA), University Hospitals of Granada-Univesity of Granada, Granada, Spain. Department of Human Anatomy and Embryology, University of Granada, Granada, Spain. [Madeddu,R]National Institute of Biostructures and Biosystem (INBB), Rome, Italy., and This work was partly supported by the Fondazione Banco di Sardegna (grant N° 2013.1308, 2014.6035 to L.G.D.), the University of Sassari (Italy), the Sardinia Region (grant N° CRP-59720 to L.G.D.), the Gianfranco del Prete Association 'The future: medicine, biology and nanotechnology Award' to L.G.D, the Instituto de Salud Carlos III (FEDER funds, grant N° PI10/02295 to J.A.M), the Consejería de Economía, Innovación y Ciencia (Junta de Andalucía, excellence grant N° (CTS-6568 to J.A.M) and by the grant N° (MAT2013-43922-R).

Subjects
Biocompatible, Polímeros, Polietilenglicoles, Erythrocytes, T-Lymphocytes, medicine.medical_treatment, Chemicals and Drugs::Organic Chemicals::Alcohols::Glycols::Ethylene Glycols::Polyethylene Glycols::Poloxamer [Medical Subject Headings], 02 engineering and technology, Linfocitos t, Leucocitos mononucleares, Lymphocyte Activation, 01 natural sciences, Monocytes, Polyethylene Glycols, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Coated Materials, Biocompatible, Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Monocytes [Medical Subject Headings], Inmunomodulación, Leukocytes, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy [Medical Subject Headings], Inmunidad innata, Ácido láctico, Poloxámero, Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes [Medical Subject Headings], Multidisciplinary, Chemistry, Citocinas, Nanocápsulas, 021001 nanoscience & nanotechnology, Lipids, Humanos, Quitosano, Cytokine, medicine.anatomical_structure, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Cell Separation::Flow Cytometry [Medical Subject Headings], Lípidos, Cytokines, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Immunomodulation [Medical Subject Headings], 0210 nano-technology, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Microscopy::Microscopy, Confocal [Medical Subject Headings], Monocitos, Biocompatibility, Cell Survival, Mononuclear, Cell Proliferation, Humans, Immune System, Leukocytes, Mononuclear, Chitosan, Nanocapsules, Chemicals and Drugs::Pharmaceutical Preparations::Dosage Forms::Drug Carriers::Nanocapsules [Medical Subject Headings], Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::Necrosis [Medical Subject Headings], Chemicals and Drugs::Lipids [Medical Subject Headings], 010402 general chemistry, Peripheral blood mononuclear cell, Article, Immune system, medicine, Phenomena and Processes::Immune System Phenomena::Immunity::Immunity, Innate [Medical Subject Headings], Inmunoterapia, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines [Medical Subject Headings], Microscopía confocal, Chemicals and Drugs::Macromolecular Substances::Polymers::Biopolymers::Chitin::Chitosan [Medical Subject Headings], Innate immune system, Monocyte, Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear [Medical Subject Headings], Coated Materials, Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Hydroxy Acids::Lactates::Lactic Acid [Medical Subject Headings], Immunotherapy, Chemicals and Drugs::Macromolecular Substances::Polymers [Medical Subject Headings], Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::Apoptosis [Medical Subject Headings], 0104 chemical sciences, Immunology, Biophysics, Chemicals and Drugs::Organic Chemicals::Alcohols::Glycols::Ethylene Glycols::Polyethylene Glycols [Medical Subject Headings], Citometría de flujo
Abstract

Lipid nanocapsules (NCs) represent promising tools in clinical practice for diagnosis and therapy applications. However, the NC appropriate functionalization is essential to guarantee high biocompatibility and molecule loading ability. In any medical application, the immune system-impact of differently functionalized NCs still remains to be fully understood. A comprehensive study on the action exerted on human peripheral blood mononuclear cells (PBMCs) and major immune subpopulations by three different NC coatings: pluronic, chitosan and polyethylene glycol-polylactic acid (PEG) is reported. After a deep particle characterization, the uptake was assessed by flow-cytometry and confocal microscopy, focusing then on apoptosis, necrosis and proliferation impact in T cells and monocytes. Cell functionality by cell diameter variations, different activation marker analysis and cytokine assays were performed. We demonstrated that the NCs impact on the immune cell response is strongly correlated to their coating. Pluronic-NCs were able to induce immunomodulation of innate immunity inducing monocyte activations. Immunomodulation was observed in monocytes and T lymphocytes treated with Chitosan-NCs. Conversely, PEG-NCs were completely inert. These findings are of particular value towards a pre-selection of specific NC coatings depending on biomedical purposes for pre-clinical investigations; i.e. the immune-specific action of particular NC coating can be excellent for immunotherapy applications.

Published
2016
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47. Mutations in the linker region of BvgS abolish response to environmental signals for the regulation of the virulence factors in Bordetella pertussis

Author

Rino Rappuoli, Riccardo Manetti, Beatrice Aricò, Vincenzo Scarlato, Manetti R., Arico B., Rappuoli R., and Scarlato V.

Subjects
Bordetella pertussis, Transcription, Genetic, Molecular Sequence Data, Mutant, Virulence, Biology, Bacterial Proteins, Transcription (biology), bvg locu, Genetics, Amino Acid Sequence, Gene, Peptide sequence, Regulation of gene expression, Promoter, Gene Expression Regulation, Bacterial, General Medicine, biology.organism_classification, Molecular biology, two-component system, Pathogenic bacteria, Mutation, environmental transcription control, Transcription Factors
Abstract

Expression of virulence factors of Bordetella pertussis is coordinately regulated by the products of the bvg locus, which codes for a sensory protein (BvgS) and a positive regulator of transcription (BvgA), a pair in the family of bacterial 'two-component' regulators. Transcription of the bvg-regulated promoters is repressed by modulating environmental factors such as 50 mM MgSO4, 10 mM nicotinic acid (NA) or low temperature (25 degrees C). We have isolated a spontaneous mutant (SK170) which expresses virulence genes at either 25 degrees C, or in the presence of 1-5 mM NA, or 10-50 mM MgSO4. Virulence factors in strain SK170 are still repressed by higher concentrations of NA (10 mM), or by a combination of low temperature (25 degrees C) and one of the other modulating agents. From this strain, we have isolated a second mutant (SK180) that showed constitutive synthesis of the virulence factors under any growth regime. Nucleotide (nt) and deduced amino acid (aa) sequence analysis showed that SK170 contains a substitution at aa570 of BvgS and SK180 contains an additional substitution at aa680. These substitutions are confined to a 161-aa sequence that links the transmembrane (TM) and kinase domains of BvgS. These mutations also alter the transcriptional autoregulation of the P1 and P2 promoters of the bvg locus. P1, which in the wild-type (wt) strain is repressed by modulating agents, is constitutively active in the mutant strains. On the contrary, P2, which is normally induced by all three modulating agents, is active in strain SK170 only in the presence of MgSO4 or NA, while in strain SK180 this promoter is repressed by modulating agents. The mutants exhibit elevated levels of the BvgA regulatory protein and have a virulent phenotype also in the presence of modulating agents.

Published
1994
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48. Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing

Author

Derek W. Hood, Tanya Mason, L Baldi, Elisa Marchetti, CL Galeotti, Sandra Nuti, E Storni, B Knapp, Guido Grandi, Marzia Monica Giuliani, Maurizio Comanducci, Roberto Manetti, E Hundt, Marirosa Mora, AC Jeffries, Gary T. Jennings, Hervé Tettelin, Enrico Luzzi, Beatrice Aricò, Giulio Ratti, Rino Rappuoli, Laura Santini, Nigel J. Saunders, M Broeker, Barbara Capecchi, Erika Bartolini, [No Value] Scarlato, Silvana Savino, E R Moxon, Dan M. Granoff, E Blair, Maria Scarselli, Mariagrazia Pizza, Masignani, J. C. Venter, PJ Zuo, Pizza M., Scarlato V., Masignani V., Giuliani M.M., Arico B., Comanducci M., Jennings G.T., Baldi L., Bartolini E., Capecchi B., Galeotti C.L., Luzzi E., Manetti R., Marchetti E., Mora M., Nuti S., Ratti G., Santini L., Savino S., Scarselli M., Storni E., Zuo P., Broeker M., Hundt E., Knapp B., Blair E., Mason T., Tettelin H., Hood D.W., Jeffries A.C., Saunders N.J., Granoff D.M., Venter J.C., Moxon E.R., Grandi G., Rappuoli R., and University of Groningen

Subjects
Serotype, OUTER-MEMBRANE PROTEIN, Surface-exposed protein, RECOMBINATION, Biology, HAEMOPHILUS-INFLUENZAE, medicine.disease_cause, DISEASE, Conserved sequence, Microbiology, vaccine candidates, NEISSERIA-MENINGITIDIS, medicine, Escherichia coli, Multidisciplinary, Neisseria meningitidis, POLYSIALIC ACID, Reverse vaccinology, Vaccine efficacy, Virology, GENE, CAPSULAR POLYSACCHARIDE, Bacterial vaccine, Vaccination, ESCHERICHIA-COLI, POPULATIONS
Abstract

Neisseria meningitidisis a major cause of bacterial septicemia and meningitis.Sequence variation of surface-exposed proteins and cross-reactivity of the serogroup B capsular polysaccharide with human tissues have hampered efforts to develop a successful vaccine. To overcome these obstacles, the entire genome sequence of a virulent serogroup B strain (MC58) was used to identify vaccine candidates. A total of 350 candidate antigens were expressed inEscherichia coli, purified, and used to immunize mice. The sera allowed the identification of proteins that are surface exposed, that are conserved in sequence across a range of strains, and that induce a bactericidal antibody response, a property known to correlate with vaccine efficacy in humans.

Published
2000

49. The small GTP binding protein rab7 is essential for cellular vacuolation induced by Helicobacter pylori cytotoxin

Author

Rino Rappuoli, Roberto Manetti, Emanuele Papini, Barbara Satin, Cesare Montecucco, Marina de Bernard, John L. Telford, Marino Zerial, Cecilia Bucci, Papini, E, Satin, B, Bucci, Cecilia, DE BERNARD, M, Telford, J, Manetti, R, Rappuoli, R, Zerial, M, and Montecucco, C.

Subjects
Endosome, Endocytic cycle, Bacterial Toxins, Vacuole, Endosomes, Biology, Endocytosis, Transfection, Membrane Fusion, General Biochemistry, Genetics and Molecular Biology, GTP Phosphohydrolases, GTP-binding protein regulators, Bacterial Proteins, GTP-Binding Proteins, Humans, Small GTPase, Molecular Biology, rab5 GTP-Binding Proteins, General Immunology and Microbiology, Helicobacter pylori, Cytotoxins, General Neuroscience, rab7 GTP-Binding Proteins, Molecular biology, Cell biology, Vacuolization, rab GTP-Binding Proteins, Mutation, Vacuoles, Rab, HeLa Cells, Research Article
Abstract

The VacA cytotoxin, produced by toxigenic strains of Helicobacter pylori, induces the formation of large vacuoles highly enriched in the small GTPase rab7. To probe the role of rab7 in vacuolization, HeLa cells were transfected with a series of rab mutants and exposed to VacA. Dominant-negative mutants of rab7 effectively prevented vacuolization, whereas homologous rab5 and rab9 mutants were only partially inhibitory or ineffective, respectively. Expression of wild-type or GTPase-deficient rab mutants synergized with VacA in inducing vacuolization. In vitro fusion of late endosomes was enhanced by active rab7 and inhibited by inactive rab7, consistent with vacuole formation by merging of late endosomes in a process that requires functional rab7. Taken together, the effects of overexpressed rab proteins described here indicate that continuous membrane flow along the endocytic pathway is necessary for vacuole growth.

Published
1997

50. Response of the bvg regulon of Bordetella pertussis to different temperatures and short-term temperature shifts

Author

Anna Prugnola, Rino Rappuoli, Vincenzo Scarlato, Riccardo Manetti, Beatrice Aricò, Prugnola A., Ario B., Manetti R., Rappuoli R., and Scarlato V.

Subjects
Bordetella pertussis, Bordetella pertussi, Environmental regulation, Hot Temperature, Time Factors, Blotting, Western, DNA Footprinting, Virulence, Biology, Regulon, Microbiology, Thermoregulation, Bacterial Proteins, Transcription (biology), Gene expression, bvg locu, Promoter, Gene Expression Regulation, Bacterial, Haemolysis, biology.organism_classification, Molecular biology, Adenylate Cyclase Toxin, Virulence genes, Cell Division, Transcription Factors
Abstract

Summary: Bordetella pertussis produces a number of virulence factors whose expression is coordinately regulated by the bvgAS locus. Transcription of virulence genes is repressed by environmental factors such as low temperature (25°C) and chemical stimuli. Temperature shift of bacterial cultures from 25°C to 37°C activates two classes of bvg-regulated virulence genes: the early genes, which are activated within 10 min, and late genes, which require 2-4 h for activation. During the interval between the activation of the early and late genes, the intracellular concentration of BvgA increases 50-fold. It has been proposed that this increased concentration may be required for the activation of the late genes. Here we have analysed the response of the bvg locus to intermediate temperatures and to repeated temperature shifts. Temperature shifts of B. pertussis cultures from 22°C to 28°C, 32°C or 35°C resulted in the synthesis of low, intermediate, and high amounts of BvgA. This implied that the intracellular concentration of BvgA is temperature-dependent. We have also observed that the amount of virulence factors produced correlates with the BvgA concentration. When bacteria grown at 37°C were shifted to 22 °C, transcription from the adenylate cyclase toxin haemolysis promoter (PAC) was repressed after 30 min, while transcription from the bvg (P1) and filamentous haemagglutinin (PFHA) promoters was repressed after 2 h. During this time, the amount of BvgA did not decrease. A subsequent temperature shift from 22°C to 37°C induced transcription from the P, and PFHA promoters after 10 min and transcription from the PAC promoter after 20 min. This result shows that in the presence of a high concentration of BvgA, the time lag between temperature shift and late promoter transcription is reduced from 2-4 h to 20 min. The above data support the proposal that the concentration of BvgA plays a role in activating expression of the late genes.

Published
1995

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