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2. Economic Consequences of Investing in Anti-HCV Antiviral Treatment from the Italian NHS Perspective: A Real-World-Based Analysis of PITER Data

Author

Marcellusi, A, Viti, R, Kondili, L, Rosato, S, Vella, S, Mennini, F, Quaranta, M, Tosti, M, Weimer, L, Ferrigno, L, D'Angelo, F, Falzano, L, Benedetti, A, Schiada, L, Cucco, M, Giacometti, A, Brescini, L, Castelletti, S, Drenaggi, D, Mazzaro, C, Angarano, G, Milella, M, Dileo, A, Rendina, M, Contaldo, A, Iannone, A, La Fortezza, F, Rizzi, M, Cologni, G, Bolondi, L, Benevento, F, Serio, I, Andreone, P, Caraceni, P, Guarneri, V, Margotti, M, Simonetti, G, Mazzella, G, Verucchi, G, Donati, V, Mian, P, Rimenti, G, Rossini, A, Contessi, G, Castelli, F, Zaltron, S, Spinetti, A, Odolini, S, Leandro, G, Cozzolongo, R, Zappimbulso, M, Russello, M, Benigno, R, Coco, C, Torti, C, Costa, C, Greco, G, Mazzitelli, M, Pisani, V, Cosco, L, Quintieri, F, Desiena, M, Giancotti, F, Vecchiet, J, Falasca, K, Mastroianni, A, Apuzzo, G, Chidichimo, L, Foschi, F, Dall'Aglio, A, Libanore, M, Segala, D, Sighinolfi, L, Bartolozzi, D, Salomoni, E, Blanc, P, Baragli, F, Delpin, B, Mariabelli, E, Mazzotta, F, Poggi, A, Zignego, A, Monti, M, Madia, F, Xheka, A, Cela, E, Santantonio, T, Bruno, S, Viscoli, C, Alessandrini, A, Curti, C, Dibiagio, A, Nicolini, L, Balletto, E, Mastroianni, C, Blerta, K, Prati, D, Raffaele, L, Andreoletti, M, Perboni, G, Costa, P, Manzini, L, Raimondo, G, Filomia, R, Lazzarin, A, Morsica, G, Salpietro, S, Puoti, M, Baiguera, C, Vassalli, S, Rumi, M, Labanca, S, Zuin, M, Giorgini, A, Orellana, D, D'Arminiomonforte, A, Debona, A, Solaro, S, Fargion, S, Valenti, L, Periti, G, Pelusi, S, Galli, M, Calvi, E, Milazzo, L, Peri, A, Lampertico, P, Borghi, M, D'Ambrosio, R, Degasperi, E, Vinci, M, Villa, E, Bernabucci, V, Bristot, L, Pereira, F, Chessa, L, Pasetto, M, Loi, M, Gori, A, Beretta, I, Pastore, V, Soria, A, Strazzabosco, M, Ciaccio, A, Gemma, M, Borgia, G, Foggia, A, Zappulo, E, Gentile, I, Buonomo, A, Abrescia, N, Maddaloni, A, Caporaso, N, Morisco, F, Camera, S, Donnarumma, L, Coppola, C, Amoruso, D, Staiano, L, Saturnino, M, Coppola, N, Martini, S, Monari, C, Federico, A, Dallio, M, Loguercio, C, Gaeta, G, Brancaccio, G, Nardone, G, Sgamato, C, D'Adamo, G, Alberti, A, Gonzo, M, Piovesan, S, Chemello, L, Buggio, A, Cavalletto, L, Barbaro, F, Castelli, E, Floreani, A, Cazzagon, N, Franceschet, I, Russo, F, Zanetto, A, Franceschet, E, Madonia, S, Cannizzaro, M, Montalto, G, Licata, A, Capitano, A, Craxi, A, Petta, S, Calvaruso, V, Rini, F, Ferrari, C, Negri, E, Orlandini, A, Pesci, M, Bruno, R, Lombardi, A, Zuccaro, V, Gulminetti, R, Asti, A, Villaraggia, M, Mondelli, M, Ludovisi, S, Baldelli, F, Di Candilo, F, Parruti, G, Di Stefano, P, Sozio, F, Gizzi, M, Brunetto, M, Colombatto, P, Coco, B, Surace, L, Foti, G, Pellicano, S, Fornaciari, G, Schianchi, S, Vignoli, P, Massari, M, Corsini, R, Garlassi, E, Ballardini, G, Andreoni, M, Cerva, C, Angelico, M, Gasbarrini, A, Siciliano, M, De Siena, M, Nosotti, L, Taliani, G, Biliotti, E, Santori, M, Spaziante, M, Tamburini, F, Vullo, V, D'Ettorre, G, Cavallari, E, Gebremeskel, T, Pavone, P, Cauda, R, Cingolani, A, Lamonica, S, D'Offizi, G, Lionetti, R, Visco Comandini, U, Grieco, A, D'Aversa, F, Picardi, A, De Vincentis, A, Galati, G, Gallo, P, Dell'Unto, C, Aghemo, A, Gatti Comini, A, Persico, M, Masarone, M, Anselmo, M, De Leo, P, Marturano, M, Brunelli, E, Ridolfi, F, Schimizzi, A, Ayoubi Khajekini, M, Framarin, L, Di Perri, G, Cariti, G, Boglione, L, Cardellino, C, Marinaro, L, Saracco, G, Ciancio, A, Toniutto, P, Alterini, G, Capra, F, Ieluzzi, D, Marcellusi A., Viti R., Kondili L. A., Rosato S., Vella S., Mennini F. S., Quaranta M. G., Tosti M. E., Weimer L. E., Ferrigno L., D'Angelo F., Falzano L., Benedetti A., Schiada L., Cucco M., Giacometti A., Brescini L., Castelletti S., Drenaggi D., Mazzaro C., Angarano G., Milella M., DiLeo A., Rendina M., Contaldo A., Iannone A., La Fortezza F., Rizzi M., Cologni G., Bolondi L., Benevento F., Serio I., Andreone P., Caraceni P., Guarneri V., Margotti M., Simonetti G., Mazzella G., Verucchi G., Donati V., Mian P., Rimenti G., Rossini A., Contessi G. B., Castelli F., Zaltron S., Spinetti A., Odolini S., Leandro G., Cozzolongo R., Zappimbulso M., Russello M., Benigno R., Coco C., Torti C., Costa C., Greco G., Mazzitelli M., Pisani V., Cosco L., Quintieri F., DeSiena M., Giancotti F., Vecchiet J., Falasca K., Mastroianni A., Apuzzo G., Chidichimo L., Foschi F. G., Dall'Aglio A. C., Libanore M., Segala D., Sighinolfi L., Bartolozzi D., Salomoni E., Blanc P., Baragli F., DelPin B., Mariabelli E., Mazzotta F., Poggi A., Zignego A. L., Monti M., Madia F., Xheka A., Cela E. M., Santantonio T. A., Bruno S. R., Viscoli C., Alessandrini A. I., Curti C., DiBiagio A., Nicolini L. A., Balletto E., Mastroianni C., Blerta K., Prati D., Raffaele L., Andreoletti M., Perboni G., Costa P., Manzini L., Raimondo G., Filomia R., Lazzarin A., Morsica G., Salpietro S., Puoti M., Baiguera C., Vassalli S., Rumi M. G., Labanca S., Zuin M., Giorgini A., Orellana D., D'ArminioMonforte A., Debona A., Solaro S., Fargion S., Valenti L., Periti G., Pelusi S., Galli M., Calvi E., Milazzo L., Peri A., Lampertico P., Borghi M., D'Ambrosio R., Degasperi E., Vinci M., Villa E., Bernabucci V., Bristot L., Pereira F., Chessa L., Pasetto M. C., Loi M., Gori A., Beretta I., Pastore V., Soria A., Strazzabosco M., Ciaccio A., Gemma M., Borgia G., Foggia A., Zappulo E., Gentile I., Buonomo A. R., Abrescia N., Maddaloni A., Caporaso N., Morisco F., Camera S., Donnarumma L., Coppola C., Amoruso D. C., Staiano L., Saturnino M. R., Coppola N., Martini S., Monari C., Federico A., Dallio M., Loguercio C., Gaeta G. B., Brancaccio G., Nardone G., Sgamato C., D'Adamo G., Alberti A., Gonzo M., Piovesan S., Chemello L., Buggio A., Cavalletto L., Barbaro F., Castelli E., Floreani A., Cazzagon N., Franceschet I., Russo F. P., Zanetto A., Franceschet E., Madonia S., Cannizzaro M., Montalto G., Licata A., Capitano A. R., Craxi A., Petta S., Calvaruso V., Rini F., Ferrari C., Negri E., Orlandini A., Pesci M., Bruno R., Lombardi A., Zuccaro V., Gulminetti R., Asti A., Villaraggia M., Mondelli M., Ludovisi S., Baldelli F., Di Candilo F., Parruti G., Di Stefano P., Sozio F., Gizzi M. C., Brunetto M. R., Colombatto P., Coco B., Surace L., Foti G., Pellicano S., Fornaciari G., Schianchi S., Vignoli P., Massari M., Corsini R., Garlassi E., Ballardini G., Andreoni M., Cerva C., Angelico M., Gasbarrini A., Siciliano M., De Siena M., Nosotti L., Taliani G., Biliotti E., Santori M., Spaziante M., Tamburini F., Vullo V., D'Ettorre G., Cavallari E. N., Gebremeskel T. S., Pavone P., Cauda R., Cingolani A., Lamonica S., D'Offizi G., Lionetti R., Visco Comandini U., Grieco A., D'Aversa F., Picardi A., De Vincentis A., Galati G., Gallo P., Dell'Unto C., Aghemo A., Gatti Comini A., Persico M., Masarone M., Anselmo M., De Leo P., Marturano M., Brunelli E., Ridolfi F., Schimizzi A. M., Ayoubi Khajekini M., Framarin L., Di Perri G., Cariti G., Boglione L., Cardellino C., Marinaro L., Saracco G. M., Ciancio A., Toniutto P., Alterini G., Capra F., Ieluzzi D., Marcellusi, A, Viti, R, Kondili, L, Rosato, S, Vella, S, Mennini, F, Quaranta, M, Tosti, M, Weimer, L, Ferrigno, L, D'Angelo, F, Falzano, L, Benedetti, A, Schiada, L, Cucco, M, Giacometti, A, Brescini, L, Castelletti, S, Drenaggi, D, Mazzaro, C, Angarano, G, Milella, M, Dileo, A, Rendina, M, Contaldo, A, Iannone, A, La Fortezza, F, Rizzi, M, Cologni, G, Bolondi, L, Benevento, F, Serio, I, Andreone, P, Caraceni, P, Guarneri, V, Margotti, M, Simonetti, G, Mazzella, G, Verucchi, G, Donati, V, Mian, P, Rimenti, G, Rossini, A, Contessi, G, Castelli, F, Zaltron, S, Spinetti, A, Odolini, S, Leandro, G, Cozzolongo, R, Zappimbulso, M, Russello, M, Benigno, R, Coco, C, Torti, C, Costa, C, Greco, G, Mazzitelli, M, Pisani, V, Cosco, L, Quintieri, F, Desiena, M, Giancotti, F, Vecchiet, J, Falasca, K, Mastroianni, A, Apuzzo, G, Chidichimo, L, Foschi, F, Dall'Aglio, A, Libanore, M, Segala, D, Sighinolfi, L, Bartolozzi, D, Salomoni, E, Blanc, P, Baragli, F, Delpin, B, Mariabelli, E, Mazzotta, F, Poggi, A, Zignego, A, Monti, M, Madia, F, Xheka, A, Cela, E, Santantonio, T, Bruno, S, Viscoli, C, Alessandrini, A, Curti, C, Dibiagio, A, Nicolini, L, Balletto, E, Mastroianni, C, Blerta, K, Prati, D, Raffaele, L, Andreoletti, M, Perboni, G, Costa, P, Manzini, L, Raimondo, G, Filomia, R, Lazzarin, A, Morsica, G, Salpietro, S, Puoti, M, Baiguera, C, Vassalli, S, Rumi, M, Labanca, S, Zuin, M, Giorgini, A, Orellana, D, D'Arminiomonforte, A, Debona, A, Solaro, S, Fargion, S, Valenti, L, Periti, G, Pelusi, S, Galli, M, Calvi, E, Milazzo, L, Peri, A, Lampertico, P, Borghi, M, D'Ambrosio, R, Degasperi, E, Vinci, M, Villa, E, Bernabucci, V, Bristot, L, Pereira, F, Chessa, L, Pasetto, M, Loi, M, Gori, A, Beretta, I, Pastore, V, Soria, A, Strazzabosco, M, Ciaccio, A, Gemma, M, Borgia, G, Foggia, A, Zappulo, E, Gentile, I, Buonomo, A, Abrescia, N, Maddaloni, A, Caporaso, N, Morisco, F, Camera, S, Donnarumma, L, Coppola, C, Amoruso, D, Staiano, L, Saturnino, M, Coppola, N, Martini, S, Monari, C, Federico, A, Dallio, M, Loguercio, C, Gaeta, G, Brancaccio, G, Nardone, G, Sgamato, C, D'Adamo, G, Alberti, A, Gonzo, M, Piovesan, S, Chemello, L, Buggio, A, Cavalletto, L, Barbaro, F, Castelli, E, Floreani, A, Cazzagon, N, Franceschet, I, Russo, F, Zanetto, A, Franceschet, E, Madonia, S, Cannizzaro, M, Montalto, G, Licata, A, Capitano, A, Craxi, A, Petta, S, Calvaruso, V, Rini, F, Ferrari, C, Negri, E, Orlandini, A, Pesci, M, Bruno, R, Lombardi, A, Zuccaro, V, Gulminetti, R, Asti, A, Villaraggia, M, Mondelli, M, Ludovisi, S, Baldelli, F, Di Candilo, F, Parruti, G, Di Stefano, P, Sozio, F, Gizzi, M, Brunetto, M, Colombatto, P, Coco, B, Surace, L, Foti, G, Pellicano, S, Fornaciari, G, Schianchi, S, Vignoli, P, Massari, M, Corsini, R, Garlassi, E, Ballardini, G, Andreoni, M, Cerva, C, Angelico, M, Gasbarrini, A, Siciliano, M, De Siena, M, Nosotti, L, Taliani, G, Biliotti, E, Santori, M, Spaziante, M, Tamburini, F, Vullo, V, D'Ettorre, G, Cavallari, E, Gebremeskel, T, Pavone, P, Cauda, R, Cingolani, A, Lamonica, S, D'Offizi, G, Lionetti, R, Visco Comandini, U, Grieco, A, D'Aversa, F, Picardi, A, De Vincentis, A, Galati, G, Gallo, P, Dell'Unto, C, Aghemo, A, Gatti Comini, A, Persico, M, Masarone, M, Anselmo, M, De Leo, P, Marturano, M, Brunelli, E, Ridolfi, F, Schimizzi, A, Ayoubi Khajekini, M, Framarin, L, Di Perri, G, Cariti, G, Boglione, L, Cardellino, C, Marinaro, L, Saracco, G, Ciancio, A, Toniutto, P, Alterini, G, Capra, F, Ieluzzi, D, Marcellusi A., Viti R., Kondili L. A., Rosato S., Vella S., Mennini F. S., Quaranta M. G., Tosti M. E., Weimer L. E., Ferrigno L., D'Angelo F., Falzano L., Benedetti A., Schiada L., Cucco M., Giacometti A., Brescini L., Castelletti S., Drenaggi D., Mazzaro C., Angarano G., Milella M., DiLeo A., Rendina M., Contaldo A., Iannone A., La Fortezza F., Rizzi M., Cologni G., Bolondi L., Benevento F., Serio I., Andreone P., Caraceni P., Guarneri V., Margotti M., Simonetti G., Mazzella G., Verucchi G., Donati V., Mian P., Rimenti G., Rossini A., Contessi G. B., Castelli F., Zaltron S., Spinetti A., Odolini S., Leandro G., Cozzolongo R., Zappimbulso M., Russello M., Benigno R., Coco C., Torti C., Costa C., Greco G., Mazzitelli M., Pisani V., Cosco L., Quintieri F., DeSiena M., Giancotti F., Vecchiet J., Falasca K., Mastroianni A., Apuzzo G., Chidichimo L., Foschi F. G., Dall'Aglio A. C., Libanore M., Segala D., Sighinolfi L., Bartolozzi D., Salomoni E., Blanc P., Baragli F., DelPin B., Mariabelli E., Mazzotta F., Poggi A., Zignego A. L., Monti M., Madia F., Xheka A., Cela E. M., Santantonio T. A., Bruno S. R., Viscoli C., Alessandrini A. I., Curti C., DiBiagio A., Nicolini L. A., Balletto E., Mastroianni C., Blerta K., Prati D., Raffaele L., Andreoletti M., Perboni G., Costa P., Manzini L., Raimondo G., Filomia R., Lazzarin A., Morsica G., Salpietro S., Puoti M., Baiguera C., Vassalli S., Rumi M. G., Labanca S., Zuin M., Giorgini A., Orellana D., D'ArminioMonforte A., Debona A., Solaro S., Fargion S., Valenti L., Periti G., Pelusi S., Galli M., Calvi E., Milazzo L., Peri A., Lampertico P., Borghi M., D'Ambrosio R., Degasperi E., Vinci M., Villa E., Bernabucci V., Bristot L., Pereira F., Chessa L., Pasetto M. C., Loi M., Gori A., Beretta I., Pastore V., Soria A., Strazzabosco M., Ciaccio A., Gemma M., Borgia G., Foggia A., Zappulo E., Gentile I., Buonomo A. R., Abrescia N., Maddaloni A., Caporaso N., Morisco F., Camera S., Donnarumma L., Coppola C., Amoruso D. C., Staiano L., Saturnino M. R., Coppola N., Martini S., Monari C., Federico A., Dallio M., Loguercio C., Gaeta G. B., Brancaccio G., Nardone G., Sgamato C., D'Adamo G., Alberti A., Gonzo M., Piovesan S., Chemello L., Buggio A., Cavalletto L., Barbaro F., Castelli E., Floreani A., Cazzagon N., Franceschet I., Russo F. P., Zanetto A., Franceschet E., Madonia S., Cannizzaro M., Montalto G., Licata A., Capitano A. R., Craxi A., Petta S., Calvaruso V., Rini F., Ferrari C., Negri E., Orlandini A., Pesci M., Bruno R., Lombardi A., Zuccaro V., Gulminetti R., Asti A., Villaraggia M., Mondelli M., Ludovisi S., Baldelli F., Di Candilo F., Parruti G., Di Stefano P., Sozio F., Gizzi M. C., Brunetto M. R., Colombatto P., Coco B., Surace L., Foti G., Pellicano S., Fornaciari G., Schianchi S., Vignoli P., Massari M., Corsini R., Garlassi E., Ballardini G., Andreoni M., Cerva C., Angelico M., Gasbarrini A., Siciliano M., De Siena M., Nosotti L., Taliani G., Biliotti E., Santori M., Spaziante M., Tamburini F., Vullo V., D'Ettorre G., Cavallari E. N., Gebremeskel T. S., Pavone P., Cauda R., Cingolani A., Lamonica S., D'Offizi G., Lionetti R., Visco Comandini U., Grieco A., D'Aversa F., Picardi A., De Vincentis A., Galati G., Gallo P., Dell'Unto C., Aghemo A., Gatti Comini A., Persico M., Masarone M., Anselmo M., De Leo P., Marturano M., Brunelli E., Ridolfi F., Schimizzi A. M., Ayoubi Khajekini M., Framarin L., Di Perri G., Cariti G., Boglione L., Cardellino C., Marinaro L., Saracco G. M., Ciancio A., Toniutto P., Alterini G., Capra F., and Ieluzzi D.

Abstract

Objective: We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy. Methods: A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulative costs saved to recover the Italian NHS investment in DAA treatment. Three different PITER enrolment periods, which covered the full DAA access evolution in Italy, were considered. Results: The disease stages of 2657 patients who consecutively underwent DAA therapy from January 2015 to December 2017 at 30 PITER clinical centres were standardized for 1000 patients. The investment in DAAs was considered to equal €25 million, €15 million, and €9 million in 2015, 2016, and 2017, respectively. For patients treated in 2015, the BPT was not achieved, because of the disease severity of the treated patients and high DAA prices. For 2016 and 2017, the estimated BPTs were 6.6 and 6.2 years, respectively. The total cost savings after 20 years were €50.13 and €55.50 million for 1000 patients treated in 2016 and 2017, respectively. Conclusions: This study may be a useful tool for public decision makers to understand how HCV clinical and epidemiological profiles influence the economic burden of HCV.

Published
2019

3. Economic Consequences of Investing in Anti-HCV Antiviral Treatment from the Italian NHS Perspective: A Real-World-Based Analysis of PITER Data

Author

Marcellusi, Andrea, Viti, Raffaella, Kondili, Loreta A., Rosato, Stefano, Vella, Stefano, Mennini, Francesco Saverio, Kondili, L. A., Vella, S., Quaranta, M. G., Rosato, S., Tosti, M. E., Weimer, L. E., Ferrigno, L., D’Angelo, F., Falzano, L., Benedetti, A., Schiadà, L., Cucco, M., Giacometti, A., Brescini, L., Castelletti, S., Drenaggi, D., Mazzaro, C., Angarano, G., Milella, M., Di Leo, A., Rendina, M., Contaldo, A., Iannone, A., La Fortezza, F., Rizzi, M., Cologni, G., Bolondi, L., Benevento, F., Serio, I., Andreone, P., Caraceni, P., Guarneri, V., Margotti, M., Simonetti, G., Mazzella, G., Verucchi, G., Donati, V., Mian, Peter, Rimenti, G., Rossini, A., Contessi, G. B., Castelli, Fulvio, Zaltron, S., Spinetti, A., Odolini, S., Leandro, G., Cozzolongo, R., Zappimbulso, M., Russello, M., Benigno, R., Coco, C., Torti, C., Costa, C., Greco, G., Mazzitelli, M., Pisani, V., Cosco, Lucia, Quintieri, F., De Siena, Martina, Giancotti, F., Vecchiet, J., Falasca, K., Mastroianni, A., Apuzzo, G., Chidichimo, L., Foschi, F. G., Dall’Aglio, A. C., Libanore, M., Segala, D., Sighinolfi, L., Bartolozzi, D., Salomoni, E., Blanc, P., Baragli, F., DelundefinedPin, B., Mariabelli, E., Mazzotta, F., Poggi, A., Zignego, A. L., Monti, M., Madia, Francesca, Xheka, A., Cela, E. M., Santantonio, T. A., Bruno, S. R., Viscoli, C., Alessandrini, A. I., Curti, C., DiundefinedBiagio, A., Nicolini, L. A., Balletto, E., Mastroianni, Chiara, Blerta, K., Prati, D., Raffaele, L., Andreoletti, M., Perboni, G., Costa, P., Manzini, L., Raimondo, G., Filomia, R., Lazzarin, A., Morsica, G., Salpietro, S., Puoti, M., Baiguera, C., Vassalli, S., Rumi, M. G., Labanca, S., Zuin, M., Giorgini, A., Orellana, D., D’ArminioundefinedMonforte, A., Debona, A., Solaro, S., Fargion, S., Valenti, L., Periti, G., Pelusi, S., Galli, M., Calvi, E., Milazzo, L., Peri, A., Lampertico, P., Borghi, Margherita, D’Ambrosio, R., Degasperi, E., Vinci, Maria Rosaria, Villa, E., Bernabucci, V., Bristot, Luca, Pereira, F., Chessa, L., Pasetto, M. C., Loi, M., Gori, A., Beretta, I., Pastore, V., Soria, A., Strazzabosco, M., Ciaccio, A., Gemma, M., Borgia, G., Foggia, A., Zappulo, E., Gentile, I., Buonomo, A. R., Abrescia, N., Maddaloni, A., Caporaso, N., Morisco, F., Camera, S., Donnarumma, L., Coppola, C., Amoruso, D. C., Staiano, L., Saturnino, M. R., Coppola, N., Martini, S., Monari, C., Federico, Alex, Dallio, M., Loguercio, C., Gaeta, G. B., Brancaccio, G., Nardone, G., Sgamato, C., D’Adamo, G., Alberti, A., Gonzo, M., Piovesan, S., Chemello, L., Buggio, A., Cavalletto, L., Barbaro, F., Castelli, Enrico, Floreani, A., Cazzagon, N., Franceschet, I., Russo, F. P., Zanetto, A., Franceschet, E., Madonia, S., Cannizzaro, Maria Chiara, Montalto, G., Licata, A., Capitano, A. R., Craxì, A., Petta, S., Calvaruso, V., Rini, F., Ferrari, C., Negri, E., Orlandini, A., Pesci, M., Bruno, R., Lombardi, A., Zuccaro, V., Gulminetti, R., Asti, A., Villaraggia, M., Mondelli, M., Ludovisi, S., Baldelli, F., Di Candilo, F., Parruti, G., Di Stefano, Paolo, Sozio, F., Gizzi, M. C., Brunetto, M. R., Colombatto, P., Coco, B., Surace, L., Foti, G., Pellicano, S., Fornaciari, G., Schianchi, S., Vignoli, P., Massari, M., Corsini, R., Garlassi, E., Ballardini, G., Andreoni, M., Cerva, C., Angelico, M., Gasbarrini, Antonio, Siciliano, M., Nosotti, L., Taliani, G., Biliotti, E., Santori, M., Spaziante, M., Tamburini, F., Vullo, V., D’Ettorre, G., Cavallari, E. N., Gebremeskel, T. S., Pavone, P., Cauda, Roberto, Cingolani, Antonella, Lamonica, S., D’Offizi, G., Lionetti, R., Visco Comandini, U., Grieco, Antonio, D’Aversa, F., Picardi, A., De Vincentis, A., Galati, G., Gallo, Patrizia, Dell’Unto, C., Aghemo, A., Gatti Comini, A., Persico, M., Masarone, M., Anselmo, M., De Leo, P., Marturano, Monia, Brunelli, E., Ridolfi, F., Schimizzi, A. M., Ayoubi Khajekini, M., Framarin, L., Di Perri, G., Cariti, G., Boglione, L., Cardellino, C., Marinaro, L., Saracco, G. M., Ciancio, A., Toniutto, P., Alterini, G., Capra, F., Ieluzzi, D., Marcellusi, A, Viti, R, Kondili, L, Rosato, S, Vella, S, Mennini, F, Quaranta, M, Tosti, M, Weimer, L, Ferrigno, L, D'Angelo, F, Falzano, L, Benedetti, A, Schiada, L, Cucco, M, Giacometti, A, Brescini, L, Castelletti, S, Drenaggi, D, Mazzaro, C, Angarano, G, Milella, M, Dileo, A, Rendina, M, Contaldo, A, Iannone, A, La Fortezza, F, Rizzi, M, Cologni, G, Bolondi, L, Benevento, F, Serio, I, Andreone, P, Caraceni, P, Guarneri, V, Margotti, M, Simonetti, G, Mazzella, G, Verucchi, G, Donati, V, Mian, P, Rimenti, G, Rossini, A, Contessi, G, Castelli, F, Zaltron, S, Spinetti, A, Odolini, S, Leandro, G, Cozzolongo, R, Zappimbulso, M, Russello, M, Benigno, R, Coco, C, Torti, C, Costa, C, Greco, G, Mazzitelli, M, Pisani, V, Cosco, L, Quintieri, F, Desiena, M, Giancotti, F, Vecchiet, J, Falasca, K, Mastroianni, A, Apuzzo, G, Chidichimo, L, Foschi, F, Dall'Aglio, A, Libanore, M, Segala, D, Sighinolfi, L, Bartolozzi, D, Salomoni, E, Blanc, P, Baragli, F, Delpin, B, Mariabelli, E, Mazzotta, F, Poggi, A, Zignego, A, Monti, M, Madia, F, Xheka, A, Cela, E, Santantonio, T, Bruno, S, Viscoli, C, Alessandrini, A, Curti, C, Dibiagio, A, Nicolini, L, Balletto, E, Mastroianni, C, Blerta, K, Prati, D, Raffaele, L, Andreoletti, M, Perboni, G, Costa, P, Manzini, L, Raimondo, G, Filomia, R, Lazzarin, A, Morsica, G, Salpietro, S, Puoti, M, Baiguera, C, Vassalli, S, Rumi, M, Labanca, S, Zuin, M, Giorgini, A, Orellana, D, D'Arminiomonforte, A, Debona, A, Solaro, S, Fargion, S, Valenti, L, Periti, G, Pelusi, S, Galli, M, Calvi, E, Milazzo, L, Peri, A, Lampertico, P, Borghi, M, D'Ambrosio, R, Degasperi, E, Vinci, M, Villa, E, Bernabucci, V, Bristot, L, Pereira, F, Chessa, L, Pasetto, M, Loi, M, Gori, A, Beretta, I, Pastore, V, Soria, A, Strazzabosco, M, Ciaccio, A, Gemma, M, Borgia, G, Foggia, A, Zappulo, E, Gentile, I, Buonomo, A, Abrescia, N, Maddaloni, A, Caporaso, N, Morisco, F, Camera, S, Donnarumma, L, Coppola, C, Amoruso, D, Staiano, L, Saturnino, M, Coppola, N, Martini, S, Monari, C, Federico, A, Dallio, M, Loguercio, C, Gaeta, G, Brancaccio, G, Nardone, G, Sgamato, C, D'Adamo, G, Alberti, A, Gonzo, M, Piovesan, S, Chemello, L, Buggio, A, Cavalletto, L, Barbaro, F, Castelli, E, Floreani, A, Cazzagon, N, Franceschet, I, Russo, F, Zanetto, A, Franceschet, E, Madonia, S, Cannizzaro, M, Montalto, G, Licata, A, Capitano, A, Craxi, A, Petta, S, Calvaruso, V, Rini, F, Ferrari, C, Negri, E, Orlandini, A, Pesci, M, Bruno, R, Lombardi, A, Zuccaro, V, Gulminetti, R, Asti, A, Villaraggia, M, Mondelli, M, Ludovisi, S, Baldelli, F, Di Candilo, F, Parruti, G, Di Stefano, P, Sozio, F, Gizzi, M, Brunetto, M, Colombatto, P, Coco, B, Surace, L, Foti, G, Pellicano, S, Fornaciari, G, Schianchi, S, Vignoli, P, Massari, M, Corsini, R, Garlassi, E, Ballardini, G, Andreoni, M, Cerva, C, Angelico, M, Gasbarrini, A, Siciliano, M, De Siena, M, Nosotti, L, Taliani, G, Biliotti, E, Santori, M, Spaziante, M, Tamburini, F, Vullo, V, D'Ettorre, G, Cavallari, E, Gebremeskel, T, Pavone, P, Cauda, R, Cingolani, A, Lamonica, S, D'Offizi, G, Lionetti, R, Visco Comandini, U, Grieco, A, D'Aversa, F, Picardi, A, De Vincentis, A, Galati, G, Gallo, P, Dell'Unto, C, Aghemo, A, Gatti Comini, A, Persico, M, Masarone, M, Anselmo, M, De Leo, P, Marturano, M, Brunelli, E, Ridolfi, F, Schimizzi, A, Ayoubi Khajekini, M, Framarin, L, Di Perri, G, Cariti, G, Boglione, L, Cardellino, C, Marinaro, L, Saracco, G, Ciancio, A, Toniutto, P, Alterini, G, Capra, F, Ieluzzi, D, Kondili LA, Vella S, Quaranta MG, Rosato S, Tosti ME, Weimer LE, Ferrigno L, D'Angelo F, Falzano L, Benedetti A, Schiadà L, Cucco M, Giacometti A, Brescini L, Castelletti S, Drenaggi D, Mazzaro C, Angarano G, Milella M, Di Leo A, Rendina M, Contaldo A, Iannone A, La Fortezza F, Rizzi M, Cologni G, Bolondi L, Benevento F, Serio I, Andreone P, Caraceni P, Guarneri V, Margotti M, Simonetti G, Mazzella G, Verucchi G, Donati V, Mian P, Rimenti G, Rossini A, Contessi GB, Castelli F, Zaltron S, Spinetti A, Odolini S, Leandro G, Cozzolongo R, Zappimbulso M, Russello M, Benigno R, Coco C, Torti C, Costa C, Greco G, Mazzitelli M, Pisani V, Cosco L, Quintieri F, De Siena M, Giancotti F, Vecchiet J, Falasca K, Mastroianni A, Apuzzo G, Chidichimo L, Foschi FG, Dall'Aglio AC, Libanore M, Segala D, Sighinolfi L, Bartolozzi D, Salomoni E, Blanc P, Baragli F, Del Pin B, Mariabelli E, Mazzotta F, Poggi A, Zignego AL, Monti M, Madia F, Xheka A, Cela EM, Santantonio TA, Bruno SR, Viscoli C, Alessandrini AI, Curti C, Di Biagio A, Nicolini LA, Balletto E, Mastroianni C, Blerta K, Prati D, Raffaele L, Andreoletti M, Perboni G, Costa P, Manzini L, Raimondo G, Filomia R, Lazzarin A, Morsica G, Salpietro S, Puoti M, Baiguera C, Vassalli S, Rumi MG, Labanca S, Zuin M, Giorgini A, Orellana D, D'Arminio Monforte A, Debona A, Solaro S, Fargion S, Valenti L, Periti G, Pelusi S, Galli M, Calvi E, Milazzo L, Peri A, Lampertico P, Borghi M, D'Ambrosio R, Degasperi E, Vinci M, Villa E, Bernabucci V, Bristot L, Pereira F, Chessa L, Pasetto MC, Loi M, Gori A, Beretta I, Pastore V, Soria A, Strazzabosco M, Ciaccio A, Gemma M, Borgia G, Foggia A, Zappulo E, Gentile I, Buonomo AR, Abrescia N, Maddaloni A, Caporaso N, Morisco F, Camera S, Donnarumma L, Coppola C, Amoruso DC, Staiano L, Saturnino MR, Coppola N, Martini S, Monari C, Federico A, Dallio M, Loguercio C, Gaeta GB, Brancaccio G, Nardone G, Sgamato C, D'Adamo G, Alberti A, Gonzo M, Piovesan S, Chemello L, Buggio A, Cavalletto L, Barbaro F, Castelli E, Floreani A, Cazzagon N, Franceschet I, Russo FP, Zanetto A, Franceschet E, Madonia S, Cannizzaro M, Montalto G, Licata A, Capitano AR, Craxì A, Petta S, Calvaruso V, Rini F, Ferrari C, Negri E, Orlandini A, Pesci M, Bruno R, Lombardi A, Zuccaro V, Gulminetti R, Asti A, Villaraggia M, Mondelli M, Ludovisi S, Baldelli F, Di Candilo F, Parruti G, Di Stefano P, Sozio F, Gizzi MC, Brunetto MR, Colombatto P, Coco B, Surace L, Foti G, Pellicano S, Fornaciari G, Schianchi S, Vignoli P, Massari M, Corsini R, Garlassi E, Ballardini G, Andreoni M, Cerva C, Angelico M, Gasbarrini A, Siciliano M, De Siena M, Nosotti L, Taliani G, Biliotti E, Santori M, Spaziante M, Tamburini F, Vullo V, D'Ettorre G, Cavallari EN, Gebremeskel TS, Pavone P, Cauda R, Cingolani A, Lamonica S, D'Offizi G, Lionetti R, Visco Comandini U, Grieco A, D'Aversa F, Picardi A, De Vincentis A, Galati G, Gallo P, Dell'Unto C, Aghemo A, Gatti Comini A, Persico M, Masarone M, Anselmo M, De Leo P, Marturano M, Brunelli E, Ridolfi F, Schimizzi AM, Ayoubi Khajekini M, Framarin L, Di Perri G, Cariti G, Boglione L, Cardellino C, Marinaro L, Saracco GM, Ciancio A, Toniutto P, Alterini G, Capra F, Ieluzzi D., Marcellusi, A., Viti, R., Kondili, L. A., Rosato, S., Vella, S., Mennini, F. S., Quaranta, M. G., Tosti, M. E., Weimer, L. E., Ferrigno, L., D'Angelo, F., Falzano, L., Benedetti, A., Schiada, L., Cucco, M., Giacometti, A., Brescini, L., Castelletti, S., Drenaggi, D., Mazzaro, C., Angarano, G., Milella, M., Dileo, A., Rendina, M., Contaldo, A., Iannone, A., La Fortezza, F., Rizzi, M., Cologni, G., Bolondi, L., Benevento, F., Serio, I., Andreone, P., Caraceni, P., Guarneri, V., Margotti, M., Simonetti, G., Mazzella, G., Verucchi, G., Donati, V., Mian, P., Rimenti, G., Rossini, A., Contessi, G. B., Castelli, F., Zaltron, S., Spinetti, A., Odolini, S., Leandro, G., Cozzolongo, R., Zappimbulso, M., Russello, M., Benigno, R., Coco, C., Torti, C., Costa, C., Greco, G., Mazzitelli, M., Pisani, V., Cosco, L., Quintieri, F., Desiena, M., Giancotti, F., Vecchiet, J., Falasca, K., Mastroianni, A., Apuzzo, G., Chidichimo, L., Foschi, F. G., Dall'Aglio, A. C., Libanore, M., Segala, D., Sighinolfi, L., Bartolozzi, D., Salomoni, E., Blanc, P., Baragli, F., Delpin, B., Mariabelli, E., Mazzotta, F., Poggi, A., Zignego, A. L., Monti, M., Madia, F., Xheka, A., Cela, E. M., Santantonio, T. A., Bruno, S. R., Viscoli, C., Alessandrini, A. I., Curti, C., Dibiagio, A., Nicolini, L. A., Balletto, E., Mastroianni, C., Blerta, K., Prati, D., Raffaele, L., Andreoletti, M., Perboni, G., Costa, P., Manzini, L., Raimondo, G., Filomia, R., Lazzarin, A., Morsica, G., Salpietro, S., Puoti, M., Baiguera, C., Vassalli, S., Rumi, M. G., Labanca, S., Zuin, M., Giorgini, A., Orellana, D., D'Arminiomonforte, A., Debona, A., Solaro, S., Fargion, S., Valenti, L., Periti, G., Pelusi, S., Galli, M., Calvi, E., Milazzo, L., Peri, A., Lampertico, P., Borghi, M., D'Ambrosio, R., Degasperi, E., Vinci, M., Villa, E., Bernabucci, V., Bristot, L., Pereira, F., Chessa, L., Pasetto, M. C., Loi, M., Gori, A., Beretta, I., Pastore, V., Soria, A., Strazzabosco, M., Ciaccio, A., Gemma, M., Borgia, G., Foggia, A., Zappulo, E., Gentile, I., Buonomo, A. R., Abrescia, N., Maddaloni, A., Caporaso, N., Morisco, F., Camera, S., Donnarumma, L., Coppola, C., Amoruso, D. C., Staiano, L., Saturnino, M. R., Coppola, N., Martini, S., Monari, C., Federico, A., Dallio, M., Loguercio, C., Gaeta, G. B., Brancaccio, G., Nardone, G., Sgamato, C., D'Adamo, G., Alberti, A., Gonzo, M., Piovesan, S., Chemello, L., Buggio, A., Cavalletto, L., Barbaro, F., Castelli, E., Floreani, A., Cazzagon, N., Franceschet, I., Russo, F. P., Zanetto, A., Franceschet, E., Madonia, S., Cannizzaro, M., Montalto, G., Licata, A., Capitano, A. R., Craxi, A., Petta, S., Calvaruso, V., Rini, F., Ferrari, C., Negri, E., Orlandini, A., Pesci, M., Bruno, R., Lombardi, A., Zuccaro, V., Gulminetti, R., Asti, A., Villaraggia, M., Mondelli, M., Ludovisi, S., Baldelli, F., Di Candilo, F., Parruti, G., Di Stefano, P., Sozio, F., Gizzi, M. C., Brunetto, M. R., Colombatto, P., Coco, B., Surace, L., Foti, G., Pellicano, S., Fornaciari, G., Schianchi, S., Vignoli, P., Massari, M., Corsini, R., Garlassi, E., Ballardini, G., Andreoni, M., Cerva, C., Angelico, M., Gasbarrini, A., Siciliano, M., De Siena, M., Nosotti, L., Taliani, G., Biliotti, E., Santori, M., Spaziante, M., Tamburini, F., Vullo, V., D'Ettorre, G., Cavallari, E. N., Gebremeskel, T. S., Pavone, P., Cauda, R., Cingolani, A., Lamonica, S., D'Offizi, G., Lionetti, R., Visco Comandini, U., Grieco, A., D'Aversa, F., Picardi, A., De Vincentis, A., Galati, G., Gallo, P., Dell'Unto, C., Aghemo, A., Gatti Comini, A., Persico, M., Masarone, M., Anselmo, M., De Leo, P., Marturano, M., Brunelli, E., Ridolfi, F., Schimizzi, A. M., Ayoubi Khajekini, M., Framarin, L., Di Perri, G., Cariti, G., Boglione, L., Cardellino, C., Marinaro, L., Saracco, G. M., Ciancio, A., Toniutto, P., Alterini, G., Capra, F., Ieluzzi, D., Marcellusi, Andrea, Viti, Raffaella, Kondili, Loreta A., Rosato, Stefano, Vella, Stefano, Mennini, Francesco Saverio, Kondili, L.A., Quaranta, M.G., Tosti, M.E., Weimer, L.E., D’Angelo, F., Schiadà, L., Di&nbsp, Leo, A., Contessi, G.B., De&nbsp, Siena, M., Foschi, F.G., Dall’Aglio, A.C., Del&nbsp, Pin, B., Zignego, A.L., Cela, E.M., Santantonio, T.A., Bruno, S.R., Alessandrini, A.I., Biagio, A., Nicolini, L.A., Rumi, M.G., D’Arminio&nbsp, Monforte, A., D’Ambrosio, R., Pasetto, M.C., Buonomo, A.R., Amoruso, D.C., Saturnino, M.R., Gaeta, G.B., D’Adamo, G., Russo, F.P., Capitano, A.R., Craxì, A., Gizzi, M.C., Brunetto, M.R., D’Ettorre, G., Cavallari, E.N., Gebremeskel, T.S., D’Offizi, G., D’Aversa, F., Dell’Unto, C., Schimizzi, A.M., Saracco, G.M., Cosco, Alfredo, Dall’Aglio, A. C., Salomoni, Valentina, Nicolini, Elvira, Calvi, Marta, Soria, Giovanni, D'Adamo, Danilo, ALONSO ALBERTI, MARIA PALOMA CARMEN, Orlandini, Giovanni, DE ASTIS, Fabio, Sozio, Concetta, Terzini, Angelico, DE SIENA, ANDREA URIEL, Taliani, Sabrina, Spaziante, Agata, Lamonica, Emilia, and Capra, Carlo

Subjects
Liver Cirrhosis, Pediatrics, Time Factors, Settore MED/09 - Medicina Interna, National Health Programs, ERADICATION, OUTBREAK, antiviral treatment, anti HCV, economic consequences, Hepacivirus, LIVER FIBROSIS, Severity of Illness Index, Health Services Accessibility, COST-EFFECTIVENESS, Indirect costs, 0302 clinical medicine, Epidemiology, virus infection, 030212 general & internal medicine, health care economics and organizations, cost effectiveness, 030503 health policy & services, Health Policy, Health services research, health, Hepatitis C, Markov Chains, chronic hepatitis C, virus infection, fibrosis progression, cost effectiveness, liver fibrosis, Italy, Pharmacology, Public Health, Environmental and Occupational Health, Cohort, Settore SECS-P/03 - Scienza delle Finanze, Disease Progression, Public Health, 0305 other medical science, Viral hepatitis, Anti-HCV antiviral treatment, CHRONIC HEPATITIS-C, medicine.medical_specialty, Genotype, Settore MED/12 - GASTROENTEROLOGIA, VIRUS-INFECTION, Antiviral Agents, NO, 03 medical and health sciences, Cost Savings, Humans, medicine, MANAGEMENT, chronic hepatitis C, INDUCED DISEASES, METAANALYSIS, Health economics, business.industry, Public health, Environmental and Occupational Health, medicine.disease, FIBROSIS PROGRESSION, business
Abstract

OBJECTIVE:\ud We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy.\ud \ud METHODS:\ud A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulative costs saved to recover the Italian NHS investment in DAA treatment. Three different PITER enrolment periods, which covered the full DAA access evolution in Italy, were considered.\ud \ud RESULTS:\ud The disease stages of 2657 patients who consecutively underwent DAA therapy from January 2015 to December 2017 at 30 PITER clinical centres were standardized for 1000 patients. The investment in DAAs was considered to equal €25 million, €15 million, and €9 million in 2015, 2016, and 2017, respectively. For patients treated in 2015, the BPT was not achieved, because of the disease severity of the treated patients and high DAA prices. For 2016 and 2017, the estimated BPTs were 6.6 and 6.2 years, respectively. The total cost savings after 20 years were €50.13 and €55.50 million for 1000 patients treated in 2016 and 2017, respectively.\ud \ud CONCLUSIONS:\ud This study may be a useful tool for public decision makers to understand how HCV clinical and epidemiological profiles influence the economic burden of HCV.

Published
2019

6. Activity Test of CLA Syntheszed from Castor Oil by in Vivo White Mice (Rattus norveginus)

Author

Minat Karya Nia Hia, Rini F. Hutabarat, Manihar Situmorang, Tita Juwitaningsih, and Marham Sitorus

Subjects
White (mutation), History, In vivo, Chemistry, Castor oil, medicine, Food science, Computer Science Applications, Education, medicine.drug
Abstract

Malondialdehyde (MDA) is a metabolite resulting from lipid peroxidation by free radicals that can be formed when hydroxyl free radicals such as Reactive Oxygen Species (ROS) react with fatty acid components of the cell membrane so that a chain reaction is known as fat peroxidation. The fat peroxidation will break the chain of fatty acids into various toxic compounds and cause damage to the cell membrane. Thus MDA is an parameter of the presence of free radicals in the body. In this research, the Conjugated Linoleic Acid (CLA) antioxidant test was synthesized from castor oil in vivo against white mice (Rattus norveginus). White mice exposed to free radicals through cigarette smoke for 2 hours per day for 14 days. Mice were given an antioxidant intake of CLA with a concentration of 200, 400, 600,800,1000 mg / body weight every day with three repetitions. The same thing is done with intake of Ascorbic acid (Vitamin C) and α-tocopherol (Vitamin E) as a comparison. As a control also made negative control without treatment and positive control by exposure to cigarette smoke without intake of antioxidants. The CLA can inhibit free radicals by reduction MDA in blood an inhibitory equivalent to Ascorbic acid (Vitamin C) and α- tocopherol (Vitamin E).

Published
2020

7. OC.07.1 DIRECT ACTING ANTIVIRALS AFTER SUCCESSFUL TREATMENT OF EARLY HEPATOCELLULAR CARCINOMA IMPROVE SURVIVAL AND REDUCE HEPATIC DECOMPENSATION IN HCV-CIRRHOTIC PATIENTS

Author

Celsa, C., primary, Cabibbo, G., additional, Calvaruso, V., additional, Petta, S., additional, Cacciola, I., additional, Cannavò, M.R., additional, Madonia, S., additional, Rossi, M., additional, Magro, B., additional, Rini, F., additional, Distefano, M., additional, Larocca, L., additional, Prestileo, T., additional, Malizia, G., additional, Bertino, G., additional, Benanti, F., additional, Licata, A., additional, Scalisi, I., additional, Mazzola, G., additional, Di Rosolini, M.A., additional, Alaimo, G., additional, Averna, A., additional, Cartabellotta, F., additional, Alessi, N., additional, Guastella, S., additional, Russello, M., additional, Scifo, G., additional, Squadrito, G., additional, Raimondo, G., additional, Craxì, A., additional, Di Marco, V., additional, and Cammà, C., additional

Published
2019
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8. AA genotype of deSNP rs6726639 of MERTK gene is associated with development of Hepatocellular Carcinoma after eradication of Hepatitis C Virus infection

Author

Di Marco, L., primary, Calvaruso, V., additional, Grimaudo, S., additional, Petta, S., additional, Pipitone, M.R., additional, Cabibbo, G., additional, Conte, E., additional, Magro, B., additional, Rini, F., additional, Celsa, C., additional, Cammà, C., additional, Craxì, A., additional, and Di Marco, V., additional

Published
2019
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10. Changes in 13C-aminopyrine breath test predict liver-related events and death in patients with HCV-related previous decompensated child A5 or child A6 to B cirrhosis who achieve SVR after DAA therapy

Author

Petta, S., primary, Rini, F., additional, Calvaruso, V., additional, Cammà, C., additional, Ciminnisi, S., additional, Di Marco, V., additional, Giannini, E., additional, Grimaudo, S., additional, Pipitone, R.M., additional, and Craxì, A., additional

Published
2019
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11. Direct acting antivirals after successful treatment of early hepatocellular carcinoma improve survival in HCV-cirrhotic patients

Author

Cabibbo, G., primary, Celsa, C., additional, Calvaruso, V., additional, Petta, S., additional, Cacciola, I., additional, Cannavò, M.R., additional, Madonia, S., additional, Rossi, M., additional, Magro, B., additional, Rini, F., additional, Distefano, M., additional, Larocca, L., additional, Prestileo, T., additional, Malizia, G., additional, Bertino, G., additional, Benanti, F., additional, Licata, A., additional, Scalisi, I., additional, Mazzola, G., additional, Di Rosolini, M.A., additional, Alaimo, G., additional, Averna, A., additional, Cartabellotta, F., additional, Alessi, N., additional, Guastella, S., additional, Russello, M., additional, Scifo, G., additional, Squadrito, G., additional, Raimondo, G., additional, Craxì, A., additional, Di Marco, V., additional, and Cammà, C., additional

Published
2019
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12. Hepatitis C Virus eradication by direct antiviral agents improves carotid atherosclerosis in patients with advanced fibrosis/compensated cirrhosis

Author

Petta, S., primary, Adinolfi, L.E., additional, Fracanzani, A.L., additional, Calvaruso, V., additional, Rini, F., additional, Camma, C., additional, Marco, V.D., additional, Giordano, M., additional, Marrone, A., additional, Nevola, R., additional, Pinto, A., additional, Rinaldi, L., additional, Torres, D., additional, Tuttolomondo, A., additional, Valenti, L., additional, Fargion, S., additional, and Craxi, A., additional

Published
2018
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13. Adaptive Immunity in Fibrosarcomatous Dermatofibrosarcoma Protuberans and Response to Imatinib Treatment

Author

Tazzari, M., Indio, V., Vergani, B., Cecco, L. De, Rini, F., Negri, T., Camisaschi, C., Fiore, M., Stacchiotti, S., Dagrada, G.P., Casali, P.G., Gronchi, A., Astolfi, A., Pantaleo, M.A., Villa, A., Lombardo, C., Arienti, F., Pilotti, S., Rivoltini, L., Castelli, C., Tazzari, M., Indio, V., Vergani, B., Cecco, L. De, Rini, F., Negri, T., Camisaschi, C., Fiore, M., Stacchiotti, S., Dagrada, G.P., Casali, P.G., Gronchi, A., Astolfi, A., Pantaleo, M.A., Villa, A., Lombardo, C., Arienti, F., Pilotti, S., Rivoltini, L., and Castelli, C.

Abstract

Item does not contain fulltext, Dermatofibrosarcoma protuberans (DFSP), although rare, is the most frequent skin sarcoma. Here, we focus on DFSP carrying the fibrosarcomatous transformation (FS-DFSP). FS-DFSP responds to imatinib (IM); however, tumor relapse often occurs. In a series of 21 pre- and post-treatment FS-DFSP samples, the present study explored the events that occur at the tumor site during IM therapy. Gene expression profile and immunohistochemistry analyses documented the occurrence of IM-induced senescence phenotype in the tumor cells and showed the accumulation of activated CD3+ T cells and CD163+CD14+ myeloid cells expressing the CD209 marker in post-therapy lesions. In post-IM specimens, the pathological response and tumor apoptosis were tightly associated with T-cell infiltration, thus suggesting the presence of an ongoing anti-tumor response, which was further confirmed by in vitro functional assays with CD3+ T cells isolated from an IM-responding FS-DFSP lesion. The integration of targeted therapies with immune therapies is currently under investigation to achieve longer tumor control. Our data outline the in situ immunological effects of IM and classify IM-treated FS-DFSP as potentially sensitive to immunotherapy, thus providing the rationale for further investigations of combination treatment for this soft-tissue sarcoma.

Published
2017

14. Adaptive Immunity in Fibrosarcomatous Dermatofibrosarcoma Protuberans and Response to Imatinib Treatment

Author

Tazzari, M, Indio, V, Vergani, B, De Cecco, L, Rini, F, Negri, T, Camisaschi, C, Fiore, M, Stacchiotti, S, Dagrada, G, Casali, P, Gronchi, A, Astolfi, A, Pantaleo, M, Villa, A, Lombardo, C, Arienti, F, Pilotti, S, Rivoltini, L, Castelli, C, Castelli, C., VERGANI, BARBARA, VILLA, ANTONELLO, Tazzari, M, Indio, V, Vergani, B, De Cecco, L, Rini, F, Negri, T, Camisaschi, C, Fiore, M, Stacchiotti, S, Dagrada, G, Casali, P, Gronchi, A, Astolfi, A, Pantaleo, M, Villa, A, Lombardo, C, Arienti, F, Pilotti, S, Rivoltini, L, Castelli, C, Castelli, C., VERGANI, BARBARA, and VILLA, ANTONELLO

Abstract

Dermatofibrosarcoma protuberans (DFSP), although rare, is the most frequent skin sarcoma. Here, we focus on DFSP carrying the fibrosarcomatous transformation (FS-DFSP). FS-DFSP responds to imatinib (IM); however, tumor relapse often occurs. In a series of 21 pre- and post-treatment FS-DFSP samples, the present study explored the events that occur at the tumor site during IM therapy. Gene expression profile and immunohistochemistry analyses documented the occurrence of IM-induced senescence phenotype in the tumor cells and showed the accumulation of activated CD3+ T cells and CD163+CD14+ myeloid cells expressing the CD209 marker in post-therapy lesions. In post-IM specimens, the pathological response and tumor apoptosis were tightly associated with T-cell infiltration, thus suggesting the presence of an ongoing anti-tumor response, which was further confirmed by in vitro functional assays with CD3+ T cells isolated from an IM-responding FS-DFSP lesion. The integration of targeted therapies with immune therapies is currently under investigation to achieve longer tumor control. Our data outline the in situ immunological effects of IM and classify IM-treated FS-DFSP as potentially sensitive to immunotherapy, thus providing the rationale for further investigations of combination treatment for this soft-tissue sarcoma.

Published
2017

16. Immunomodulatory Factors Control the Fate of Melanoma Tumor Initiating Cells

Author

Tuccitto, A., Tazzari, M., Beretta, V., Rini, F., Miranda, C., Greco, A, Santinami, M., Patuzzo, R., Vergani, B., Villa, A., Manenti, G., Cleris, L., Giardiello, D., Alison, M., Rivoltini, L., Castelli, C., Perego, M., Tuccitto, A., Tazzari, M., Beretta, V., Rini, F., Miranda, C., Greco, A, Santinami, M., Patuzzo, R., Vergani, B., Villa, A., Manenti, G., Cleris, L., Giardiello, D., Alison, M., Rivoltini, L., Castelli, C., and Perego, M.

Abstract

Item does not contain fulltext, Melanoma is a highly heterogeneous tumor for which recent evidence supports a model of dynamic stemness. Melanoma cells might temporally acquire tumor-initiating properties or switch from a status of tumor-initiating cells (TICs) to a more differentiated one depending on the tumor context. However, factors driving these functional changes are still unknown. We focused on the role of cyto/chemokines in shaping TICs isolated directly from tumor specimens of two melanoma patients, namely Me14346S and Me15888S. We analyzed the secretion profile of TICs and of their corresponding melanoma differentiated cells and we tested the ability of cyto/chemokines to influence TIC self-renewal and differentiation. We found that TICs, grown in vitro as melanospheres, had a complex secretory profile as compared to their differentiated counterparts. Some factors, such as CCL-2 and IL-8, also produced by adherent melanoma cells and melanocytes did not influence TIC properties. Conversely, IL-6, released by differentiated cells, reduced TIC self-renewal and induced TIC differentiation while IL-10, produced by Me15888S, strongly promoted TIC self-renewal through paracrine/autocrine actions. Complete neutralization of IL-10 activity by gene silencing and antibody-mediated blocking of the IL-10Ralpha was required to sensitize Me15888S to IL-6-induced differentiation. For the first time these results show that functional heterogeneity of melanoma could be directly influenced by inflammatory and suppressive soluble factors, with IL-6 favoring TIC differentiation, and IL-10 supporting TIC self-renewal. Thus, understanding the tumor microenvironment (TME) role in modulating melanoma TIC phenotype is fundamental to identifying novel therapeutic targets to achieve long-lasting regression of metastatic melanoma. Stem Cells 2016;34:2449-2460.

Published
2016

18. Melan-A/MART-1 immunity in a EWS-ATF1 translocated clear cell sarcoma patient treated with sunitinib: A case report

Author

Tazzari, M, Palassini, E, Vergani, B, Villa, A, Rini, F, Negri, T, Colombo, C, Crippa, F, Morosi, C, Casali, P, Pilotti, S, Stacchiotti, S, Rivoltini, L, Castelli, C, Castelli, C., VERGANI, BARBARA, VILLA, ANTONELLO, Tazzari, M, Palassini, E, Vergani, B, Villa, A, Rini, F, Negri, T, Colombo, C, Crippa, F, Morosi, C, Casali, P, Pilotti, S, Stacchiotti, S, Rivoltini, L, Castelli, C, Castelli, C., VERGANI, BARBARA, and VILLA, ANTONELLO

Abstract

Background: Clear cell sarcoma (CCS), initially named malignant melanoma of soft parts, is an aggressive soft tissue sarcoma (STS) that, due to MITF activation, shares with melanoma the expression of melanocyte differentiation antigens. CCS is poorly sensitive to chemotherapy. Multi-kinase inhibitors have been used as therapeutic agents. In the case we report here, treatment with sunitinib induced a long-lasting clinical response that was associated with an immune activation directed against Melan-A/MART-1 antigen. Case presentation: A 28years old female patient with an advanced molecularly confirmed CCS resistant to conventional chemotherapy was started in January 2012 on sunitinib, 37.5mg/day, with evidence of radiologic and metabolic response at the primary and metastatic sites of disease. Pathologic response and loss of the Melan-A/MART-1 antigen were evidenced on residual tumor removed in April 2012. Immunological monitoring performed on patient's blood during pharmacological treatment revealed a systemic, Melan-A/MART-1 specific immunity and a low frequency of immunosuppressive cells. Sunitinib was restarted in May 2012, with a new response, and continued for 11months although with repeatedly interruptions due to toxicity. Disease progression and new responses were documented at each treatment interruption and restart. Sunitinib was definitively interrupted in April 2013 for disease progression. Conclusion: The analysis of this case proves that antigens expressed by CCS, as for melanoma, can be immunogenic in vivo and that tumor-antigen specific T cells may exert anti-tumor activity in CCS patient. Thus, manipulation of the immune response may have therapeutic potential for this STS subtype and immunotherapy approaches, can be promising therapeutic options for these patients.

Published
2015

21. Inorganic component of saliva during fasting and after fast break

Author

Nurul Waqiah Mas’ud, Arsmin Nur Idul Fitri, Rasmidar Samad, Rini F Lestari, Yusrini Selviani, and Atikah Balqis Ferry

Subjects
medicine.medical_specialty, Saliva, Component (thermodynamics), Chemistry, 030206 dentistry, lcsh:RK1-715, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, lcsh:Dentistry, Internal medicine, medicine, 030212 general & internal medicine, Food science, Saliva, Inorganic, Fasting
Abstract

Oral health is closely related to salivary components. Saliva consists of water, inorganic and organic materials. Fasting changes one’s meal and drinking time that in turn can affect the environment in oral cavity, including inorganic componenet of saliva. The purpose of this study is to determine the inorganic component of saliva during fasting and after fast break. The study is an observational analytic (longitudinal/follow-up study) conducted in Hasanuddin University dental hospital in July 2015. The sampling method is purposive sampling with the entire population of Dental Public Health section students, who are 35 people with 16 research subjects who fullfill the criteria of the study. Samples were tested in the laboratory using Atomic Absorption Spectrophotometer (AAS) in part per million (ppm) units. The data is analysed by paired t-test with SPSS version 17.0. The result shows that concentration of inorganic components (calcium, phosphate and potassium) in the saliva decreased significantly after fast break (p

Published
2016

22. Adaptive immune contexture at the tumour site and downmodulation of circulating myeloid-derived suppressor cells in the response of solitary fibrous tumour patients to anti-angiogenic therapy

Author

Tazzari, M, Negri, T, Rini, F, Vergani, B, Huber, V, Villa, A, Dagrada, P, Colombo, C, Fiore, M, Gronchi, A, Stacchiotti, S, Casali, P, Pilotti, S, Rivoltini, L, Castelli, C, Castelli, C., VERGANI, BARBARA, VILLA, ANTONELLO, Tazzari, M, Negri, T, Rini, F, Vergani, B, Huber, V, Villa, A, Dagrada, P, Colombo, C, Fiore, M, Gronchi, A, Stacchiotti, S, Casali, P, Pilotti, S, Rivoltini, L, Castelli, C, Castelli, C., VERGANI, BARBARA, and VILLA, ANTONELLO

Abstract

Host immunity is emerging as a key player in the prognosis and response to treatment of cancer patients. However, the impact of the immune system and its modulation by therapies are unknown in rare soft tissue sarcomas such as solitary fibrous tumours (SFTs), whose management in the advanced forms includes anti-angiogenic therapy. Here, we studied the in situ and systemic immune status of advanced SFT patients and the effects of sunitinib malate (SM) in association with the clinical efficacy. Immune contexture of SFTs was assessed by immunohistochemistry in lesions from untreated or SM-treated patients. Frequency of circulating myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs) and T-cell functions was assessed ex vivo in SFT patients prior and during anti-angiogenic therapy. Patients with long-term tumour control were included to correlate immune profiles and clinical responses. Anti-angiogenic naïve SFT lesions were heavily infiltrated by CD163(+)CD14(+)CD68(-) and CD163(+)CD14(-)CD68(-) myeloid cells but devoid of T cells. Conversely, post-SM tumours acquired a new subset of CD68(+)CD14(+) myeloid cells and displayed traits of an on-going adaptive immunity, strongly enriched in activated CD8(+) and CD4(+) T cells. These changes at the tumour site paralleled the alleviation of systemic immunosuppression and the drop in the frequency of circulating monocytic MDSCs (mMDSCs) and granulocytic MDSCs (gMDSCs). Rebound in the number of mMDSCs, but not of gMDSCs occurred at disease progression, and a reduced percentages of mMDSCs, comparable to those found in healthy donors (HDs), endured only in the SM-responsive patients. The immune contexture of SFT patients is heavily involved in anti-angiogenic therapy and it could be exploited to achieve more durable disease control through immune-based combination strategies.

Published
2014

23. [Rad-Esito: new informational additions in the integration of content of hospital discharge cards for acute patients]

Author

Rini, F, Piscioneri, C, Consolante, C, and Fara, G M

Subjects
Aged, 80 and over, Male, Outcome Assessment, Quality Assurance, Health Care, Rome, Myocardial Infarction, Length of Stay, Middle Aged, Aged, Female, Hospital Records, Hospitalization, Humans, Medical Records, Outcome Assessment, Health Care, Patient Discharge, Survival Rate, Coronary Artery Bypass, Femoral Neck Fractures, Health Care, 80 and over, Quality Assurance
Abstract

Since the January 2008 the tracking of additional information about hospital discharge card's content has been activated in Latium. The new data, noticed by RAD-Esito card, regard the hospitalizations for acute myocardial infarction, femoral neck fracture and coronary artery bypass surgery. This study's objective has been to evaluate the quality of the data collected with the new card, at the end of the 1st semester of experimentation, concerning two institutes of care of Latium, the Casilino Polyclinic (ASL Rome B) and the Anzio-Nettuno hospital (Assembled Hospitals, ASL Rome H). Furthermore, any significant correlation's existence between a few variables for acute myocardial infarction and femoral fracture with the mortality rate and the average hospitalization period has been statistically verified. This study's preliminary results show how the integration of the hospital informative flow with the new clinical variables will be able to allow the promotion of the quality in the coding of the diagnosis and procedures, according to the current international innovations. This additional information will also be able to support the regional appropriateness and outcome of the treatments evaluation programs.

Published
2009

24. La Consulta degli Specializzandi SItI presenta: 'È come te lo aspettavi?'

Author

Tantucci, L., Bartolini, R., Bentivegna, R., Brambilla, R., Cantù, A. P., Caputo, D., Cattogno, F., Chiesa, M., Corsi, R., Di Nola, A., Dinelli, F., Fanti, M., Farneti, F., Gianfagna, Francesco, Lazzari, C., Luciano, M., Mascellini, D., Matricoti, F., Mazzini, E., Molè, A., Montanari, K., Palombo, A., Pasqualetto, C., Pucci, D., Rini, F., Schieppati, S., Vigiani, N., Vitale, A., Busilacchi, G., and Esposto, E.

Subjects
Formazione professionale, Epidemiologia, Public Health
Published
2007

26. La Consulta degli Specializzandi SItI: quali aspettative?

Author

Torri, E., Schieppati, S., Bartolini, R., Bentivegna, R., Bulegato, L., Cattogno, F., Cecchini, M., Corsi, R., Di Benedetto, C., Di Legami, V., Di Nola, A., Esposto, E., Fanti, M., Franchi, S., Gallo, A., Gallo, E., Gianfagna, Francesco, Gregoretti, B., Lazzari, C., Luciano, M., Maccari, F., Marani Toro, P., Marano, E., Molè, A., Mazzini, E., Orizio, G., Pagani, G., Palla, S., Paudice, A., Pedote, P., Piras, G., Rini, F., Salemi, M., Segagli, L., Vigiani, N., Vitale, A., Zerman, T., and Tantucci, L.

Subjects
Formazione professionale, Public Health
Published
2007

28. Adaptive immune contexture at the tumour site and downmodulation of circulating myeloid-derived suppressor cells in the response of solitary fibrous tumour patients to anti-angiogenic therapy

Author

Tazzari, M, primary, Negri, T, additional, Rini, F, additional, Vergani, B, additional, Huber, V, additional, Villa, A, additional, Dagrada, P, additional, Colombo, C, additional, Fiore, M, additional, Gronchi, A, additional, Stacchiotti, S, additional, Casali, P G, additional, Pilotti, S, additional, Rivoltini, L, additional, and Castelli, C, additional

Published
2014
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33. Recognition of melanoma-derived antigens by CTL: possible mechanisms involved in down-regulating anti-tumor T-cell reactivity

Author

Rivoltini, L, Loftus, D J, Squarcina, P, Castelli, C, Rini, F, Arienti, F, Belli, F, Marincola, F M, Geisler, C, Borsatti, A, Appella, E, Parmiani, G, Rivoltini, L, Loftus, D J, Squarcina, P, Castelli, C, Rini, F, Arienti, F, Belli, F, Marincola, F M, Geisler, C, Borsatti, A, Appella, E, and Parmiani, G

Abstract

Udgivelsesdato: 1998-null, Several T cell-recognized epitopes presented by melanoma cells have been identified recently. Despite the large array of epitopes potentially available for clinical use, it is still unclear which of these antigens could be effective in mediating anti-tumor responses when used as a vaccine. Preliminary studies showed that immunization of melanoma patients with epitopes derived from proteins of the MAGE family may result in significant clinical regressions. However, no sign of systemic immunization could be observed in peripheral blood of treated patients. Conversely, significant immunization (detected as increased antigen-specific CTL activity in peripheral blood) was obtained by vaccinating HLA-A2.1+ melanoma patients with the immunodominant epitope (residues 27-35) of the differentiation antigen MART-1, but this immunization was not accompanied by a significant clinical response. To implement immunotherapeuties capable of significantly impacting disease outcome, it is necessary to identify the potential mechanisms responsible for the failure of some antigens to mediate significant anti-tumor responses in vivo. In the case of the MART-1(27-35) epitope, we hypothesize that one of these mechanisms may be related to the existence of natural analogs of this peptide in other human normal proteins.

Published
1998

35. The nitroimidazoles as radiosensitizers and cytotoxic agents

Author

Hall, E. J., Miller, R., Astro, M., and Rini, F.

Subjects
Oxygen, Radiation-Sensitizing Agents, Cell Transformation, Neoplastic, Cell Survival, Nitrofurans, Nitroimidazoles, Cells, Cultured, Research Article
Abstract

Using hamster cells in culture, the radiosensitizing and cytotoxic properties of 8 electron-affinic drugs have been compared. These include nitrofurans derivatives as well as 2 and 5-nitroimidazoles. Most work has been performed with misonidazole for which it appears that, at 37 degree C, the concentration of drug required to produce a given level of cell killing is inversely proportional to the square of the exposure time. Misonidazole was also compared with X-rays for its ability to produce neoplastic transformations in vitro, using the C3H 10T 1/2 cell line.

Published
1978

44. Impact of hepatitis C virus clearance by direct-acting antiviral treatment on the incidence of major cardiovascular events: A prospective multicentre study

Author

Vito Di Marco, Vincenza Calvaruso, Salvatore Petta, Mariarosaria Saturnino, Riccardo Nevola, Pia Clara Pafundi, Ferdinando Carlo Sasso, Carmine Coppola, Graziano Troina, Aldo Marrone, Francesca Rini, Laura Staiano, Anna Ludovica Fracanzani, Barbara Guerrera, Mauro Giordano, Luigi Elio Adinolfi, Vincenzo Narciso, Rosa Lombardi, Luca Rinaldi, Antonio Craxì, Antonio Solano, Adinolfi L.E., Petta S., Fracanzani A.L., Coppola C., Narciso V., Nevola R., Rinaldi L., Calvaruso V., Staiano L., Di Marco V., Marrone A., Pafundi P.C., Solano A., Lombardi R., Sasso F.C., Saturnino M., Rini F., Guerrera B., Troina G., Giordano M., Craxi A., Adinolfi, Luigi Elio, Petta, Salvatore, Ludovica Fracanzani, Anna, Coppola, Carmine, Narciso, Vincenzo, Nevola, Riccardo, Rinaldi, Luca, Calvaruso, Vincenza, Staiano, Laura, Di Marco, Vito, Marrone, Aldo, Clara Pafundi, Pia, Solano, Antonio, Lombardi, Rosa, Sasso, Ferdinando Carlo, Saturnino, Mariarosaria, Rini, Francesca, Guerrera, Barbara, Troina, Graziano, Giordano, Mauro, and Craxì, Antonio

Subjects
Liver Cirrhosis, Male, 0301 basic medicine, Cirrhosis, Myocardial Ischemia, Comorbidity, Hepacivirus, Disease, 030204 cardiovascular system & hematology, Chronic hepatitis C, medicine.disease_cause, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Prospective Studies, Ischemic heart disease, Ischemic cerebral stroke, Chronic hepatitis C, Cirrhosis, Incidence, Incidence (epidemiology), Smoking, Middle Aged, Viral Load, Stroke, Italy, Hypertension, Female, Cardiology and Cardiovascular Medicine, Direct acting, medicine.medical_specialty, Ischemic heart disease, Hepatitis C virus, Hypercholesterolemia, Antiviral Agents, 03 medical and health sciences, Diabetes mellitus, Internal medicine, Diabetes Mellitus, medicine, Humans, Viremia, Aged, Cirrhosi, business.industry, Cholesterol, Hepatitis C, Chronic, medicine.disease, 030104 developmental biology, chemistry, Relative risk, Ischemic cerebral stroke, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business
Abstract

Background and aims: HCV is associated with an increased risk of cardiovascular events (CV). Whether HCV clearance by direct-acting antivirals (DAA) reduces incident CV disease is poorly understood. We investigate whether HCV eradication reduces CV events. Methods: In a prospective multicentre study, 2204 HCV patients (F0–F2:29.5%, F3–F4: 70.5%) were enrolled. Males were 48%, median age was 68 (59–74) years and BMI 25.9 (23.1–28); 24.7% were smokers, 18% had diabetes, 13.2% had cholesterol levels >200 mg/dl and 9.1% took statins, 44% had hypertension. During an overall median follow-up of 28 (24–39) months, incident CV events, such as ischemic heart disease (IHD) and ischemic cerebral stroke (ICS), were recorded. An overall of 2204 patients were evaluated as control group and 1668 patients after HCV elimination were followed as a case group. Factors associated with CV events were evaluated by uni- and multi-variate analyses. Results: Incident CV rates per 100 patient years in pre-treatment and untreated controls and treated cases were 1.12, 1.14 and 0.44 (p = 0.0001 vs. controls), respectively, and a decreased of relative risk (RR = 0.379; p = 0.0002) was observed. CV risk was 2.0–3.5 times lower then in controls (HR 3.671; 95%C.I.:1.871–7.201; p < 0.001). The calculated number of patients to be treated to get a benefit in a patient was 55.26. The annual incidence reduction of CV events was 0.68%. HCV clearance was independently associated with CV events reduction (OR, 4.716; 95% C.I.:1.832–12.138; p = 0.001). Conclusions: HCV clearance by DAA reduces CV events (IHD and ICS) with both clinical and socio-economic benefits.

Published
2020

45. Point‐of‐care HCV RNA testing in the setting of DAA therapy: HCV‐FiS (HEpatitis C Virus Fingerstick Study)

Author

Vito Di Marco, Elisabetta Conte, Antonio Craxì, Salvatore Petta, Vincenza Calvaruso, Giada Reina, Donatella Ferraro, Francesca Rini, Bianca Magro, Fabrizio Bronte, Calvaruso V., Bronte F., Ferraro D., Reina G., Conte E., Rini F., Magro B., Petta S., Di Marco V., and Craxi A.

Subjects
Male, medicine.medical_specialty, End of therapy, Fingerstick, Hepatitis C virus, Hepacivirus, medicine.disease_cause, Antiviral Agents, Internal medicine, TaqMan, medicine, Outpatient setting, Humans, HCV, DAA, Aged, Point of care, Hepatology, business.industry, Venous blood sample, Middle Aged, Viral Load, Hepatitis C, Point-of-Care Testing, RNA, Viral, Female, business, Viral load
Abstract

HCV-RNA assessment during therapy with Direct-Acting Antiviral (DAA) regimens still relies on assays requiring blood collection and transport to a specialised laboratory, which may compromise linkage to care. GeneXpert-HCV Viral Load (GXHVL) (Cepheid) is a plasma-based assay used at point of care (POC) with a sensitivity of ≤10IU/mL, and, results available within 2hours. Fifty-nine consecutive HCV-patients ready for DAAs treatment were enrolled. HCV-RNA was simultaneously tested using Roche TaqMan RT-PCR (venous blood sample) and GXHVL (capillary blood collected by fingerstick), at baseline (BL), week 4 (W4) of therapy, end of therapy (EOT) and week 12 of follow-up (W12FU). Both assays demonstrated undetectable HCV-RNA in all patients at EOT and identified the single case of HCV-relapse at W12FU. GXHVL used as a point-of-care assay in the outpatient setting provides results fully comparable to the laboratory-based test. Its excellent performance and ease of use suggest its adoption in non-specialist settings where simplicity of care is paramount to implement HCV eradication campaigns.

Published
2019

46. Reduced incidence of type 2 diabetes in patients with chronic hepatitis C virus infection cleared by direct-acting antiviral therapy: A prospective study

Author

Antonio Solano, Anna Ludovica Fracanzani, Ferdinando Carlo Sasso, Salvatore Petta, Pia Clara Pafundi, Antonio Craxì, Riccardo Nevola, Barbara Guerrera, Carmine Coppola, Vito Di Marco, Rosa Lombardi, Vincenzo Narciso, Aldo Marrone, Vincenza Calvaruso, Luigi Elio Adinolfi, Luca Rinaldi, Mariarosaria Saturnino, Mauro Giordano, Francesca Rini, Laura Staiano, Graziano Troina, Adinolfi L.E., Petta S., Fracanzani A.L., Nevola R., Coppola C., Narciso V., Rinaldi L., Calvaruso V., Pafundi P.C., Lombardi R., Staiano L., Di Marco V., Solano A., Marrone A., Saturnino M., Rini F., Guerrera B., Troina G., Giordano M., Craxi A., Sasso F.C., Adinolfi, Luigi E, Petta, Salvatore, Fracanzani, Anna L, Nevola, Riccardo, Coppola, Carmine, Narciso, Vincenzo, Rinaldi, Luca, Calvaruso, Vincenza, Pafundi, Pia Clara, Lombardi, Rosa, Staiano, Laura, Di Marco, Vito, Solano, Antonio, Marrone, Aldo, Saturnino, Mariarosaria, Rini, Francesca, Guerrera, Barbara, Troina, Graziano, Giordano, Mauro, Craxì, Antonio, and Sasso, Ferdinando C

Subjects
medicine.medical_specialty, Cirrhosis, endocrine system diseases, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, Antiviral Agents, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, chronic hepatiti, Internal medicine, Internal Medicine, medicine, Humans, Glucose homeostasis, Prospective Studies, Prospective cohort study, direct-acting antiviral, business.industry, Incidence, Incidence (epidemiology), nutritional and metabolic diseases, Type 2 Diabetes Mellitus, Hepatitis C, Chronic, medicine.disease, Diabetes Mellitus, Type 2, Case-Control Studies, Relative risk, HCV, Population study, type 2 diabetes, business, cirrhosi
Abstract

Aim HCV infection increases the risk of type 2 diabetes mellitus (T2DM). However, it remains still unclear whether HCV clearance by direct-acting antivirals (DAA) reduces T2DM. Therefore, the effect of HCV eradication on T2DM incidence was assessed. Methods A prospective multicenter case-control study was performed, which included 2,426 HCV patients, 42% of which with liver fibrosis F0-F2 and 58% F3-F4. Study population consisted of a control group including 1099 untreated patients and 1327 cases treated with DAA. T2DM incidence was assessed during a follow-up median period of 30 [IQR: 28-42] months. Risk factors of T2DM were assessed by Cox regression model (Relative risk (RR), Hazard risk (HR), Kaplan-Meier). Insulin sensitivity was evaluated by HOMA and changes by ANOVA for repeated measurements. Factors independently associated with T2DM were assessed by multivariate analysis RESULTS: The absolute incidence of T2DM/1,000 person-years for controls and cases was 28 and 7, respectively (p=0.001). In cases compared to controls, HCV clearance reduced the RR and HR of T2DM by 81% and 75-93% respectively (p = 0.001). It has been calculated that for every 15 patients who obtained HCV clearance one case of T2DM is saved. HCV clearance was associated with a significant reduction in HOMA-IR and HOMA- β and an increase in HOMA-S as assessed in 384 patients before and after HCV clearance. At multivariate analysis, HCV clearance emerged as independently associated with a reduced T2DM risk. Conclusion HCV clearance by DAA treatment reduces T2DM incidence more likely by restoring the HCV-induced alteration of glucose homeostasis mechanisms. This article is protected by copyright. All rights reserved.

Published
2020

47. Hepatitis C virus eradication by direct antiviral agents abates oxidative stress in patients with advanced liver fibrosis

Author

Salvatore Petta, Rosaria Maria Pipitone, Francesca Rini, Alfio Distefano, Agnieszka Micek, Giovanni Li Volti, Stefania Grimaudo, Carlo Castruccio Castracani, Federico Salomone, Michelino Di Rosa, Concetta Gardi, Vito Di Marco, Antonio Craxì, Vincenza Calvaruso, Salomone F., Petta S., Micek A., Pipitone R.M., Distefano A., Castruccio Castracani C., Rini F., Di Rosa M., Gardi C., Calvaruso V., Di Marco V., Li Volti G., Grimaudo S., and Craxi A.

Subjects
Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, Hepatitis C virus, isoprostanes, Hepacivirus, medicine.disease_cause, Antiviral Agents, Carotid Intima-Media Thickness, Gastroenterology, 03 medical and health sciences, Liver disease, 0302 clinical medicine, atherosclerosi, Fibrosis, Settore BIO/13 - Biologia Applicata, Internal medicine, medicine, Humans, intima-media thickness, Aged, Retrospective Studies, Settore MED/12 - Gastroenterologia, Hepatology, business.industry, cirrhosis, Carotid ultrasonography, lipid peroxidation, Middle Aged, medicine.disease, Hepatitis C, Isoprostanes, atherosclerosis, F, 2, Oxidative Stress, Intima-media thickness, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, business, Oxidative stress, cirrhosi
Abstract

Background and aims: HCV eradication improves non-hepatic outcomes such as cardiovascular diseases, although without clearly defined mechanisms. In this study we aimed to assess whether improvement of carotid atherosclerosis may be linked to a reduction in systemic oxidative stress after viral clearance. Methods: We studied a retrospective cohort of 105 patients (age 62.4±11.2years; 62 men) with F3/F4 fibrosis, characterized by carotid ultrasonography at baseline and at sustained virologic response (SVR) follow-up. Levels of 8-iso-prostaglandin F2α (F2-isoprostanes) and other oxidative stress markers were measured on frozen sera. Association between change (denoted as Δ) in oxidative stress markers (exposures) and change in carotid intima-media thickness (cIMT) (outcome) was examined using multiple linear regression. Results: Subclinical atherosclerosis, defined as the presence of carotid plaque and/or cIMT≥0.9, was present in 72% of the cohort. All patients achieved SVR that led to reduction in cIMT (0.92±0.20 vs 0.83±0.21mm, P&nbsp

Published
2020

48. Direct-acting antivirals after successful treatment of early hepatocellular carcinoma improve survival in HCV-cirrhotic patients

Author

A. Averna, Rete Sicilia Selezione Terapia – Hcv, Giovanni Raimondo, F. Cartabellotta, Salvatore Guastella, Giuseppe Alaimo, Vito Di Marco, Bianca Magro, Giovanni Mazzola, L. Larocca, M.R. Cannavò, Anna Licata, Gaetano Bertino, Salvatore Madonia, Irene Cacciola, Marco Distefano, Giuseppe Cabibbo, G. Scifo, N. Alessi, Giovanni Squadrito, Antonio Craxì, Franco Trevisani, Salvatore Petta, Margherita Rossi, Maurizio Russello, Francesca Rini, Calogero Cammà, Maria Antonietta Di Rosolini, Ciro Celsa, Giuseppe Malizia, Tullio Prestileo, Vincenza Calvaruso, I. Scalisi, F. Benanti, Cabibbo G., Celsa C., Calvaruso V., Petta S., Cacciola I., Cannavo M.R., Madonia S., Rossi M., Magro B., Rini F., Distefano M., Larocca L., Prestileo T., Malizia G., Bertino G., Benanti F., Licata A., Scalisi I., Mazzola G., Di Rosolini M.A., Alaimo G., Averna A., Cartabellotta F., Alessi N., Guastella S., Russello M., Scifo G., Squadrito G., Raimondo G., Trevisani F., Craxi A., Di Marco V., Camma C., and Cammà Calogero.

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Survival rate, Carcinoma, Hepatocellular, Cirrhosis, Sustained Virologic Response, Prognosi, Hepatitis C virus (HCV), Hepatocellular carcinoma (HCC), Direct-acting antiviral (DAA), Overall survival, Prognosis, Survival rate, Liver cirrhosis, Hepacivirus, Antiviral Agents, Gastroenterology, Liver cirrhosi, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Early Hepatocellular Carcinoma, Overall survival, Prospective Studies, Hepatocellular carcinoma (HCC), Propensity Score, Aged, Aged, 80 and over, Hepatology, business.industry, Liver Neoplasms, Hazard ratio, Direct-acting antiviral (DAA), Hepatitis C, Hepatitis C virus (HCV), Middle Aged, medicine.disease, Prognosis, Liver cirrhosis, 030104 developmental biology, Hepatocellular carcinoma, Female, 030211 gastroenterology & hepatology, Neoplasm Recurrence, Local, Liver cancer, business, Viral hepatitis, Follow-Up Studies
Abstract

Background & Aims: The effectiveness of direct-acting antivirals (DAAs) against hepatitis C virus (HCV), following successful treatment of early hepatocellular carcinoma (HCC), has been studied extensively. However, the benefit in terms of overall survival (OS) remains to be conclusively demonstrated. The aim of this study was to assess the impact of DAAs on OS, HCC recurrence, and hepatic decompensation. Methods: We prospectively enrolled 163 consecutive patients with HCV-related cirrhosis and a first diagnosis of early Barcelona Clinic Liver Cancer stage 0/A HCC, who had achieved a complete radiologic response after curative resection or ablation and were subsequently treated with DAAs. DAA-untreated patients from the ITA.LI.CA. cohort (n = 328) served as controls. After propensity score matching, outcomes of 102 DAA-treated (DAA group) and 102 DAA-untreated patients (No DAA group) were compared. Results: In the DAA group, 7/102 patients (6.9%) died, HCC recurred in 28/102 patients (27.5%) and hepatic decompensation occurred in 6/102 patients (5.9%), after a mean follow-up of 21.4 months. OS was significantly higher in the DAA group compared to the No DAA group (hazard ratio [HR] 0.39; 95% CI 0.17–0.91; p = 0.03). HCC recurrence was not significantly different between the DAA and No DAA groups (HR 0.70; 95% CI 0.44–1.13; p = 0.15). A significant reduction in the rate of hepatic decompensation was observed in the DAA group compared with the No DAA group (HR 0.32; 95% CI 0.13–0.84; p = 0.02). In the DAA group, sustained virologic response was a significant predictor of OS (HR 0.02; 95% CI 0.00–0.19; p

Published
2019

49. Aminopyrine breath test predicts liver-related events and death in HCV-related cirrhosis on SVR after DAA therapy

Author

Calogero Cammà, Vito Di Marco, Francesca Rini, S. Ciminnisi, Vincenza Calvaruso, Rosaria Maria Pipitone, Salvatore Petta, Antonio Craxì, Edoardo G. Giannini, Stefania Grimaudo, Petta S., Rini F., Calvaruso V., Camma C., Ciminnisi S., Di Marco V., Giannini E.G., Grimaudo S., Maria Pipitone R., and Craxi A.

Subjects
Liver Cirrhosis, medicine.medical_specialty, Cirrhosis, Sofosbuvir, Hepatitis C virus, Hepacivirus, medicine.disease_cause, Antiviral Agents, Gastroenterology, Internal medicine, Humans, Medicine, Decompensation, Aminopyrine, Child, CIRRHOSIS, Hepatic encephalopathy, aminopyrine breath test, Breath test, Hepatology, medicine.diagnostic_test, direct antiviral agent, Cumulative dose, business.industry, Hepatitis C, Chronic, medicine.disease, Hepatitis C, Breath Tests, liver function, Liver function, business, DIRECT ANTIVIRAL AGENTS, AMINOPYRINE BREATH TEST, LIVER FUNCTION, medicine.drug, cirrhosi
Abstract

Background & Aims: In patients with hepatitis C virus (HCV)-related advanced cirrhosis, the effects of sustained virological response (SVR) by direct antiviral agents (DAAs) on decompensation and liver deaths are less clearcut, since up to 30% of patients do not improve, and no predictors of outcome have been identified. We used 13C-aminopyrine breath test (ABT) to assess whether its changes can predict liver-related outcomes after DAA treatment in patients with HCV cirrhosis. Methods: Fifty consecutive patients with HCV cirrhosis were enrolled. Patients were included if they had Child A cirrhosis at risk for decompensation – defined as Child A6 (N=22, 44%) or previous decompensation (N=7, 14%) – or Child B cirrhosis (N=21, 42%) eligible for DAA-based antiviral therapy. ABT was performed at baseline and 12weeks after the end of antiviral therapy. Patients received sofosbuvir-based regimens. Results: Aminopyrine breath test was available for all 50 patients at baseline. The 120’ cumulative dose was directly associated at regression analysis only with albumin levels (P=.001). ABT was available at follow-up week 12 for 41 patients (FUW12), all with SVR, and followed for a median of 25.2months (range 12.2-32.1months). Lower Ʌ ABT – defined as changes of 120’ cumulative dose from FUW12 to baseline – (HR 0.97, 95% CI 0.94-0.99; P=.02) and FUW12 hepatic encephalopathy (HR 19.0, 95% CI 1.16-310.3; P=.03) were the only independent predictors of liver events/death at multivariate Cox regression analysis. The AUC of Ʌ ABT was good (0.87, 95% CI 0.75-0.97), with a delta ≥0% well discriminating patients at lower vs patients at higher risk of liver-related events/death (P&nbsp

Published
2019

50. Hepatobiliary phase in cirrhotic patients with different Model for End-stage Liver Disease score: comparison of the performance of gadoxetic acid to gadobenate dimeglumine

Author

Claudia Khouri Chalouhi, Federica Vernuccio, Angelo Vanzulli, Francesca Rini, Bruno Tuscano, Piergiorgio Duca, Giuseppe Brancatelli, Khouri Chalouhi C., Vernuccio F., Rini F., Duca P., Tuscano B., Brancatelli G., and Vanzulli A.

Subjects
Liver Cirrhosis, Adult, Male, Gadolinium DTPA, Gadoxetic acid, medicine.medical_specialty, Liver Cirrhosi, Contrast Media, Sensitivity and Specificity, Severity of Illness Index, 030218 nuclear medicine & medical imaging, Gadobenic acid, 03 medical and health sciences, Liver disease, Young Adult, 0302 clinical medicine, Model for End-Stage Liver Disease, Meglumine, Retrospective Studie, medicine, Gadolinium ethoxybenzyl DTPA, Organometallic Compounds, Humans, Radiology, Nuclear Medicine and imaging, Retrospective Studies, Neuroradiology, Aged, Aged, 80 and over, Cross-Sectional Studie, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, General Medicine, Odds ratio, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Cross-Sectional Studies, 030220 oncology & carcinogenesis, Female, Radiology, Nuclear medicine, business, medicine.drug, Human
Abstract

The purpose of this study was to compare the performance of gadobenate dimeglumine–enhanced MRI and gadoxetic acid–enhanced MRI in the hepatobiliary phase (HBP) in cirrhotic patients with different degrees of liver dysfunction. In this retrospective cross-sectional study, we analyzed the unenhanced phase and the HBP of 131 gadobenate dimeglumine–enhanced MRI examinations (gadobenate dimeglumine group) and 127 gadoxetic acid–enhanced MRI examinations (gadoxetic acid group) performed in 249 cirrhotic patients (181 men and 68 women; mean age, 64.8 years) from August 2011 to April 2017. For each MRI, the contrast enhancement index of the liver parenchyma was calculated and correlated to the Model For End-Stage Liver Disease (MELD) score (multiple linear regression analysis). A qualitative analysis of the adequacy of the HBP, adjusted for the MELD score (logistic regression analysis), was performed. The contrast enhancement index was inversely related (r = − 0.013) with MELD score in both gadoxetic acid and gadobenate dimeglumine group. At the same MELD score, the contrast enhancement index in the gadoxetic acid group was increased by a factor of 0.23 compared to the gadobenate dimeglumine group (p 10, if the hepatobiliary phase is clinically indicated. • In patients with high MELD score (> 15), the administration of the hepatobiliary agent could be useless; even though, if it is clinically indicated, we recommend to use gadoxetic acid given the higher probability of obtaining clinically relevant information.

Published
2019

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