33 results on '"Digaetano M."'
Search Results
2. Ceftolozane/Tazobactam for Treatment of Severe ESBL-Producing
- Author
-
Bassetti, M., Vena, A., Giacobbe, D. R., Falcone, M., Tiseo, G., Giannella, M., Pascale, R., Meschiari, M., Digaetano, M., Oliva, A., Rovelli, C., Carannante, N., Losito, A. R., Carbonara, S., Mariani, M. F., Mastroianni, A., Angarano, G., Tumbarello, M., Tascini, C., Grossi, P., Mastroianni, C. M., Mussini, C., Viale, P., Menichetti, F., Viscoli, C., Russo, A., Verdenelli, S., Fabiani, S., Castaldo, N., Pecori, D., Carnellutti, A., Givone, F., Graziano, E., Merelli, M., Cadeo, B., Peghin, M., Cattelan, A., Cipriani, L., Coletto, D., Gianluca, R., Ciardi, M. R., Ajassa, C., Tieghi, T., Pontino, P., Raffaelli, F., Artioli, S., Caruana, G., Luzzati, R., Bontempo, G., Petrosillo, N., Capone, A., Rizzardini, G., Coen, M., Passerini, M., Guadagnino, G., Urso, F., Borgia, G., Gentile, I., Maraolo, A. E., Crapis, M., Venturini, S., Parruti, G., Trave, F., Girardis, M., Cascio, A., Gioe, C., Anselmo, M., Malfatto, E., Bassetti, Matteo, Vena, Antonio, Giacobbe, Daniele Roberto, Falcone, Marco, Tiseo, Giusy, Giannella, Maddalena, Pascale, Renato, Meschiari, Marianna, Digaetano, Margherita, Oliva, Alessandra, Rovelli, Cristina, Carannante, Novella, Losito, Angela Raffaella, Carbonara, Sergio, Mariani, Michele Fabiano, Mastroianni, Antonio, Angarano, Gioacchino, Tumbarello, Mario, Tascini, Carlo, Grossi, Paolo, Mastroianni, Claudio Maria, Mussini, Cristina, Viale, Pierluigi, Menichetti, Francesco, Viscoli, Claudio, Russo, Alessandro, Bassetti M., Vena A., Giacobbe D.R., Falcone M., Tiseo G., Giannella M., Pascale R., Meschiari M., Digaetano M., Oliva A., Rovelli C., Carannante N., Losito A.R., Carbonara S., Mariani M.F., Mastroianni A., Angarano G., Tumbarello M., Tascini C., Grossi P., Mastroianni C.M., Mussini C., Viale P., Menichetti F., Viscoli C., Russo A., Verdenelli S., Fabiani S., Castaldo N., Pecori D., Carnellutti A., Givone F., Graziano E., Merelli M., Cadeo B., Peghin M., Cattelan A., Cipriani L., Coletto D., Gianluca R., Ciardi M.R., Ajassa C., Tieghi T., Pontino P., Raffaelli F., Artioli S., Caruana G., Luzzati R., Bontempo G., Petrosillo N., Capone A., Rizzardini G., Coen M., Passerini M., Guadagnino G., Urso F., Borgia G., Gentile I., Maraolo A.E., Crapis M., Venturini S., Parruti G., Trave F., Girardis M., Cascio A., Gioe C., Anselmo M., Malfatto E., Russo, Alessandro &, and Luzzati, R.
- Subjects
medicine.medical_specialty ,ceftolozane/tazobactam ,medicine.medical_treatment ,CRRT ,Tazobactam ,Enterobacterales ,Enterobacterale ,Internal medicine ,ESBL ,septic shock ,Major Article ,medicine ,Clinical endpoint ,Renal replacement therapy ,business.industry ,Septic shock ,Retrospective cohort study ,Odds ratio ,medicine.disease ,Ceftolozane/tazobactam ,AcademicSubjects/MED00290 ,Infectious Diseases ,Oncology ,Ceftolozane ,business ,Empiric therapy ,medicine.drug - Abstract
Background Few data are reported in the literature about the outcome of patients with severe extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) infections treated with ceftolozane/tazobactam (C/T), in empiric or definitive therapy. Methods A multicenter retrospective study was performed in Italy (June 2016–June 2019). Successful clinical outcome was defined as complete resolution of clinical signs/symptoms related to ESBL-E infection and lack of microbiological evidence of infection. The primary end point was to identify predictors of clinical failure of C/T therapy. Results C/T treatment was documented in 153 patients: pneumonia was the most common diagnosis (n = 46, 30%), followed by 34 cases of complicated urinary tract infections (22.2%). Septic shock was observed in 42 (27.5%) patients. C/T was used as empiric therapy in 46 (30%) patients and as monotherapy in 127 (83%) patients. Favorable clinical outcome was observed in 128 (83.7%) patients; 25 patients were considered to have failed C/T therapy. Overall, 30-day mortality was reported for 15 (9.8%) patients. At multivariate analysis, Charlson comorbidity index >4 (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.9–3.5; P = .02), septic shock (OR, 6.2; 95% CI, 3.8–7.9; P < .001), and continuous renal replacement therapy (OR, 3.1; 95% CI, 1.9–5.3; P = .001) were independently associated with clinical failure, whereas empiric therapy displaying in vitro activity (OR, 0.12; 95% CI, 0.01–0.34; P < .001) and adequate source control of infection (OR, 0.42; 95% CI, 0.14–0.55; P < .001) were associated with clinical success. Conclusions Data show that C/T could be a valid option in empiric and/or targeted therapy in patients with severe infections caused by ESBL-producing Enterobacterales. Clinicians should be aware of the risk of clinical failure with standard-dose C/T therapy in septic patients receiving CRRT.
- Published
- 2020
3. Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial
- Author
-
François-Xavier Lescure, Hitoshi Honda, Robert A Fowler, Jennifer Sloane Lazar, Genming Shi, Peter Wung, Naimish Patel, Owen Hagino, Ignacio J. Bazzalo, Marcelo M. Casas, Sebastián A. Nuñez, Yael Pere, Carlos M. Ibarrola, Marco A. Solis Aramayo, Maria C. Cuesta, Andrea E. Duarte, Pablo M. Gutierrez Fernandez, Maria A. Iannantuono, Erica A. Miyazaki, Javier P. Silvio, Dario G. Scublinsky, Alessandra Bales, Daniela Catarino, Elie Fiss, Sara Mohrbacher, Victor Sato, Antonio Baylao, Adilson Cavalcante, Francini Correa, Celso A. de Andrade, Juvencio Furtado, Nelson Ribeiro Filho, Valéria Telles, Leopoldo T. Trevelin, Ricardo Vipich, Rodrigo Boldo, Paula Borges, Suzana Lobo, Graziela Luckemeyer, Luana Machado, Maysa B. Alves, Ana C. Iglessias, Marianna M. Lago, Daniel W. Santos, Hugo Chapdelaine, Emilia L. Falcone, Rahima Jamal, Me-Linh Luong, Madeleine Durand, Stephane Doucet, François-Martin Carrier, Bryan A. Coburn, Lorenzo Del Sorbo, Sharon L. Walmsley, Sara Belga, Luke Y. Chen, Allison D. Mah, Theodore Steiner, Alissa J. Wright, J. Hajek, Neill Adhikari, Robert A. Fowler, Nick Daneman, Kosar A. Khwaja, Jason Shahin, Carolina Gonzalez, Rafael Silva, Marcelo Lindh, Gabriel Maluenda, Patricia Fernandez, Maite Oyonarte, Martin Lasso, Alexandre Boyer, Didier Bronnimann, Hoang-Nam Bui, Charles Cazanave, Helene Chaussade, Arnaud Desclaux, Mailys Ducours, Alexandre Duvignaud, Denis Malvy, Lisa Martin, Didier Neau, Duc Nguyen, Thierry Pistone, Gaetane Soubrane-Wirth, Julie Leitao, Clotilde Allavena, Charlotte Biron, Sabelline Bouchez, Benjamin Gaborit, Antoine Gregoire, Paul Le Turnier, Anne-Sophie Lecompte, Raphael Lecomte, Maeva Lefebvre, Francois Raffi, David Boutoille, Pascale H. Morineau, Romain Guéry, Emmanuel Chatelus, Nathalie Dumoussaud, Renaud Felten, Florina Luca, Bernard Goichot, Francis Schneider, Marie-Caroline Taquet, Matthieu Groh, Mathilde Roumier, Mathilde Neuville, Antoine Bachelard, Valentina Isernia, F-Xavier Lescure, Bao-Chau Phung, Anne Rachline, Aurelie Sautereau, Dorothee Vallois, Yves Bleher, Delphine Boucher, Clémentine Coudon, Jean Esnault, Thomas Guimard, Sophie Leautez-Nainville, Dominique Merrien, Marine Morrier, Pauline Motte-Vincent, Romain Gabeff, Hélène Leclerc, Céline Cozic, Romain Decours, Ronan Février, Gwenhael Colin, Sophie Abgrall, Dorothee Vignes, Raluca Sterpu, Mira Kuellmar, Melanie Meersch-Dini, Raphael Weiss, Alexander Zarbock, Christiane Antony, Marc Berger, Thorsten Brenner, Christian Taube, Frank Herbstreit, Sebastian Dolff, Margarethe Konik, Karsten Schmidt, Markus Zettler, Oliver Witzke, Boris Boell, Jorge Garcia Borrega, Philipp Koehler, Thomas Zander, Fabian Dusse, Othman Al-Sawaf, Philipp Köhler, Dennis Eichenauer, Matthias Kochanek, Alexander Shimabukuro-Vornhagen, Sibylle Mellinghoff, Annika Claßen, Jan-Michel Heger, Charlotte Meyer-Schwickerath, Paul Liedgens, Katrin Heindel, Ana Belkin, Asaf Biber, Mayan Gilboa, Itzchak Levy, Vladislav Litachevsky, Galia Rahav, Anat Finesod Wiedner, Tal Zilberman-Daniels, Yonatan Oster, Jacob Strahilevitz, Sigal Sviri, Elena M. Baldissera, Corrado Campochiaro, Giulio Cavalli, Lorenzo Dagna, Giacomo De Luca, Emanuel Della Torre, Alessandro Tomelleri, Davide Bernasconi De Luca, Amedeo F. Capetti, Massimo Coen, Maria V. Cossu, Massimo Galli, Andrea Giacomelli, Guido A. Gubertini, Stefano Rusconi, Giulia J. Burastero, Margherita Digaetano, Giovanni Guaraldi, Marianna Meschiari, Cristina Mussini, Cinzia Puzzolante, Sara Volpi, Marina Aiello, Alarico Ariani, Alfredo A. Chetta, Annalisa Frizzelli, Andrea Ticinesi, Domenico Tuttolomondo, Stefano Aliberti, Francesco B. Blasi, Marta F. Di Pasquale, Sofia Misuraca, Tommaso Pilocane, Edoardo Simonetta, Alessio M. Aghelmo, Claudio Angelini, Enrico Brunetta, Giorgio W. Canonica, Michele Ciccarelli, Sara Dal Farra, Maria De Santis, Sebastian Ferri, Marco Folci, Giacomo M. Guidelli, Enrico M. Heffler, Ferdinando Loiacono, Giacomo Malipiero, Giovanni Paoletti, Rosa Pedale, Francesca A. Puggioni, Francesca Racca, Aurora Zumbo, Morihiko Satou, Tatyana Lisun, Denis Protsenko, Nikolay Rubtsov, Irina Beloglazova, Daria Fomina, Mariana Lysenko, Sofia Serdotetskova, Vitali Firstov, Ivan Gordeev, Ilia Kokorin, Ksenia Komissarova, Nina Lapochkina, Elena Luchinkina, Valentin Malimon, Sevinch Mamedguseyinova, Ksenia Polubatonova, Natalia Suvorova, Jose Arribas, Alberto M. Borobia Perez, Fernando de la Calle Prieto, Juan Carlos Figueira, Rocio Motejano Sanchez, Marta Mora-Rillo, Concepcion Prados Sanchez, Javier Queiruga Parada, Francisco Fernandez Arnalich, Maria Guerro Barrientos, Alejandro Bendala Estrada, Aranzazu Caballero Marcos, Maria E. Garcia Leoni, Rita García-Martínez, Ana María Collado, Patricia Munoz Garcia, Ana Torres do Rego, María V. Villalba García, Almudena Burrillo, Maricela Valerio Minero, Paloma Gijon Vidaurreta, Sonsoles Infante Herrero, Elena Velilla, Marina Machado, Maria Olmedo, Blanca Pinilla, Benito Almirante Gragera, Maria de la Esperanza Cañas Ruano, Sofia Contreras Medina, Alejandro Cortés Herrera, Vicenç Falcó Ferrer, Ricard Ferrer Roca, Xavier Nuvials Casals, Esteve Ribera Pascuet, Paula Suanzes Diez, Pedro Rebollo Castro, Felipe Garcia Alcaide, Alejandro Soriano, Aina Oliver Caldes, Ana González Cordón, Celia Cardozo, Lorena De la Mora Cañizo, Romina Pena López, Sandra Chamorro, Clara Crespillo-Andujar, Rosa Escudero Sanchez, Jesús Fortún-Abete, Begoña Monge-Maillo, Ana Moreno Zamora, Francesca Norman, Matilde Sanchez Conde, Sergio Serrano Villar, Pilar Vizcarra, Lescure, F. -X., Honda, H., Fowler, R. A., Lazar, J. S., Shi, G., Wung, P., Patel, N., Hagino, O., Bazzalo, I. J., Casas, M. M., Nunez, S. A., Pere, Y., Ibarrola, C. M., Solis Aramayo, M. A., Cuesta, M. C., Duarte, A. E., Gutierrez Fernandez, P. M., Iannantuono, M. A., Miyazaki, E. A., Silvio, J. P., Scublinsky, D. G., Bales, A., Catarino, D., Fiss, E., Mohrbacher, S., Sato, V., Baylao, A., Cavalcante, A., Correa, F., de Andrade, C. A., Furtado, J., Ribeiro Filho, N., Telles, V., Trevelin, L. T., Vipich, R., Boldo, R., Borges, P., Lobo, S., Luckemeyer, G., Machado, L., Alves, M. B., Iglessias, A. C., Lago, M. M., Santos, D. W., Chapdelaine, H., Falcone, E. L., Jamal, R., Luong, M. -L., Durand, M., Doucet, S., Carrier, F. -M., Coburn, B. A., Del Sorbo, L., Walmsley, S. L., Belga, S., Chen, L. Y., Mah, A. D., Steiner, T., Wright, A. J., Hajek, J., Adhikari, N., Daneman, N., Khwaja, K. A., Shahin, J., Gonzalez, C., Silva, R., Lindh, M., Maluenda, G., Fernandez, P., Oyonarte, M., Lasso, M., Boyer, A., Bronnimann, D., Bui, H. -N., Cazanave, C., Chaussade, H., Desclaux, A., Ducours, M., Duvignaud, A., Malvy, D., Martin, L., Neau, D., Nguyen, D., Pistone, T., Soubrane-Wirth, G., Leitao, J., Allavena, C., Biron, C., Bouchez, S., Gaborit, B., Gregoire, A., Le Turnier, P., Lecompte, A. -S., Lecomte, R., Lefebvre, M., Raffi, F., Boutoille, D., Morineau, P. H., Guery, R., Chatelus, E., Dumoussaud, N., Felten, R., Luca, F., Goichot, B., Schneider, F., Taquet, M. -C., Groh, M., Roumier, M., Neuville, M., Bachelard, A., Isernia, V., Phung, B. -C., Rachline, A., Sautereau, A., Vallois, D., Bleher, Y., Boucher, D., Coudon, C., Esnault, J., Guimard, T., Leautez-Nainville, S., Merrien, D., Morrier, M., Motte-Vincent, P., Gabeff, R., Leclerc, H., Cozic, C., Decours, R., Fevrier, R., Colin, G., Abgrall, S., Vignes, D., Sterpu, R., Kuellmar, M., Meersch-Dini, M., Weiss, R., Zarbock, A., Antony, C., Berger, M., Brenner, T., Taube, C., Herbstreit, F., Dolff, S., Konik, M., Schmidt, K., Zettler, M., Witzke, O., Boell, B., Garcia Borrega, J., Koehler, P., Zander, T., Dusse, F., Al-Sawaf, O., Kohler, P., Eichenauer, D., Kochanek, M., Shimabukuro-Vornhagen, A., Mellinghoff, S., Classen, A., Heger, J. -M., Meyer-Schwickerath, C., Liedgens, P., Heindel, K., Belkin, A., Biber, A., Gilboa, M., Levy, I., Litachevsky, V., Rahav, G., Finesod Wiedner, A., Zilberman-Daniels, T., Oster, Y., Strahilevitz, J., Sviri, S., Baldissera, E. M., Campochiaro, C., Cavalli, G., Dagna, L., De Luca, Giacomo., Della Torre, E., Tomelleri, A., Bernasconi De Luca, D., Capetti, A. F., Coen, M., Cossu, M. V., Galli, M., Giacomelli, A., Gubertini, G. A., Rusconi, S., Burastero, G. J., Digaetano, M., Guaraldi, G., Meschiari, M., Mussini, C., Puzzolante, C., Volpi, S., Aiello, M., Ariani, A., Chetta, A. A., Frizzelli, A., Ticinesi, A., Tuttolomondo, D., Aliberti, S., Blasi, F. B., Di Pasquale, M. F., Misuraca, S., Pilocane, T., Simonetta, E., Aghelmo, A. M., Angelini, C., Brunetta, E., Canonica, G. W., Ciccarelli, M., Dal Farra, S., De Santis, M., Ferri, S., Folci, M., Guidelli, G. M., Heffler, E. M., Loiacono, F., Malipiero, G., Paoletti, G., Pedale, R., Puggioni, F. A., Racca, F., Zumbo, A., Satou, M., Lisun, T., Protsenko, D., Rubtsov, N., Beloglazova, I., Fomina, D., Lysenko, M., Serdotetskova, S., Firstov, V., Gordeev, I., Kokorin, I., Komissarova, K., Lapochkina, N., Luchinkina, E., Malimon, V., Mamedguseyinova, S., Polubatonova, K., Suvorova, N., Arribas, J., Borobia Perez, A. M., de la Calle Prieto, F., Figueira, J. C., Motejano Sanchez, R., Mora-Rillo, M., Prados Sanchez, C., Queiruga Parada, J., Fernandez Arnalich, F., Guerro Barrientos, M., Bendala Estrada, A., Caballero Marcos, A., Garcia Leoni, M. E., Garcia-Martinez, R., Collado, A. M., Munoz Garcia, P., Torres do Rego, A., Villalba Garcia, M. V., Burrillo, A., Valerio Minero, M., Gijon Vidaurreta, P., Infante Herrero, S., Velilla, E., Machado, M., Olmedo, M., Pinilla, B., Almirante Gragera, B., Canas Ruano, M. D. L. E., Contreras Medina, S., Cortes Herrera, A., Falco Ferrer, V., Ferrer Roca, R., Nuvials Casals, X., Ribera Pascuet, E., Suanzes Diez, P., Rebollo Castro, P., Garcia Alcaide, F., Soriano, A., Oliver Caldes, A., Gonzalez Cordon, A., Cardozo, C., De la Mora Canizo, L., Pena Lopez, R., Chamorro, S., Crespillo-Andujar, C., Escudero Sanchez, R., Fortun-Abete, J., Monge-Maillo, B., Moreno Zamora, A., Norman, F., Sanchez Conde, M., Serrano Villar, S., and Vizcarra, P.
- Subjects
Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Critical Care ,International Cooperation ,Population ,Antibodies, Monoclonal, Humanized ,Placebo ,Severity of Illness Index ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,Intensive care ,Severity of illness ,medicine ,Clinical endpoint ,Humans ,Immunologic Factors ,030212 general & internal medicine ,Mortality ,education ,Respiratory Distress Syndrome ,education.field_of_study ,Dose-Response Relationship, Drug ,SARS-CoV-2 ,business.industry ,Hazard ratio ,COVID-19 ,Articles ,Middle Aged ,Receptors, Interleukin-6 ,Sarilumab ,Treatment Outcome ,030228 respiratory system ,Female ,Drug Monitoring ,Cytokine Release Syndrome ,business - Abstract
Summary Background Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group. Interpretation This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19. Funding Sanofi and Regeneron Pharmaceuticals.
- Published
- 2021
4. The impact of tocilizumab on respiratory support states transition and clinical outcomes in COVID-19 patients. A Markov model multi-state study
- Author
-
Giovanni Guaraldi, Gianluca Cuomo, Marianna Meschiari, Andrea Cossarizza, Massimo Girardis, Cristina Mussini, Stefano Busani, Luca Corradi, Alessandro Raimondi, Erica Bacca, Erica Franceschini, Giovanni Dolci, Margherita Digaetano, Antonella Santoro, Giacomo Ciusa, Dina Yaacoub, Marianna Menozzi, Sara Volpi, Marco Tutone, Cinzia Puzzolante, Gabriella Orlando, Giacomo Franceschi, Jovana Milic, Andrea Bedini, Licia Gozzi, Federico Banchelli, Vittorio Iadisernia, Giulia Burastero, Roberto D'Amico, Federica Carli, Matteo Faltoni, Rossella Miglio, Carlotta Rogati, Milic J., Banchelli F., Meschiari M., Franceschini E., Ciusa G., Gozzi L., Volpi S., Faltoni M., Franceschi G., Iadisernia V., Yaacoub D., Dolci G., Bacca E., Rogati C., Tutone M., Burastero G., Raimondi A., Menozzi M., Cuomo G., Corradi L., Orlando G., Santoro A., Digaetano M., Puzzolante C., Carli F., Bedini A., Busani S., Girardis M., Cossarizza A., Miglio R., Mussini C., Guaraldi G., and D'Amico R.
- Subjects
Male ,medicine.medical_specialty ,Respiratory Therapy ,Time Factors ,Time Factor ,medicine.medical_treatment ,Science ,Antibodies, Monoclonal, Humanized ,law.invention ,chemistry.chemical_compound ,Tocilizumab ,Randomized controlled trial ,law ,Oxygen therapy ,Internal medicine ,medicine ,Humans ,Aged ,Mechanical ventilation ,Multidisciplinary ,Noninvasive Ventilation ,business.industry ,Mortality rate ,Oxygen Inhalation Therapy ,COVID-19 ,Markov Chain ,Middle Aged ,medicine.disease ,Respiration, Artificial ,Markov Chains ,COVID-19 Drug Treatment ,Pneumonia ,Treatment Outcome ,chemistry ,Breathing ,Medicine ,Observational study ,Female ,business ,Research Article ,Human - Abstract
Background The benefit of tocilizumab on mortality and time to recovery in people with severe COVID pneumonia may depend on appropriate timing. The objective was to estimate the impact of tocilizumab administration on switching respiratory support states, mortality and time to recovery. Methods In an observational study, a continuous-time Markov multi-state model was used to describe the sequence of respiratory support states including: no respiratory support (NRS), oxygen therapy (OT), non-invasive ventilation (NIV) or invasive mechanical ventilation (IMV), OT in recovery, NRS in recovery. Results Two hundred seventy-one consecutive adult patients were included in the analyses contributing to 695 transitions across states. The prevalence of patients in each respiratory support state was estimated with stack probability plots, comparing people treated with and without tocilizumab since the beginning of the OT state. A positive effect of tocilizumab on the probability of moving from the invasive and non-invasive mechanical NIV/IMV state to the OT in recovery state (HR = 2.6, 95% CI = 1.2–5.2) was observed. Furthermore, a reduced risk of death was observed in patients in NIV/IMV (HR = 0.3, 95% CI = 0.1–0.7) or in OT (HR = 0.1, 95% CI = 0.0–0.8) treated with tocilizumab. Conclusion To conclude, we were able to show the positive impact of tocilizumab used in different disease stages depicted by respiratory support states. The use of the multi-state Markov model allowed to harmonize the heterogeneous mortality and recovery endpoints and summarize results with stack probability plots. This approach could inform randomized clinical trials regarding tocilizumab, support disease management and hospital decision making.
- Published
- 2021
5. Evaluating immunological and inflammatory changes of treatment-experienced people living with HIV switching from first-line triple cART regimens to DTG/3TC vs. B/F/TAF: the DEBATE trial.
- Author
-
Cossarizza A, Cozzi-Lepri A, Mattioli M, Paolini A, Neroni A, De Biasi S, Tartaro DL, Borella R, Fidanza L, Gibellini L, Beghetto B, Roncaglia E, Nardini G, Milic J, Menozzi M, Cuomo G, Digaetano M, Orlando G, Borghi V, Guaraldi G, and Mussini C
- Subjects
- Humans, Interleukin-6, Tenofovir therapeutic use, Lamivudine therapeutic use, CD4-CD8 Ratio, HIV Infections
- Abstract
Background: The aim of this randomized clinical trial (RCT) was to compare immunological changes in virally suppressed people living with HIV (PLWH) switching from a three-drug regimen (3DR) to a two-drug regimen (2DR)., Methods: An open-label, prospective RCT enrolling PLWH receiving a 3DR who switched to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir/lamivudine (DTG/3TC) was performed. Blood was taken at baseline and months 6 and 12. The primary outcome was the change in CD4+ or CD8+ T-cell counts and CD4/CD8 ratio over time points. The secondary outcomes were the changes in immunological and inflammatory parameters. Parametric mixed-linear models with random intercepts and slopes were fitted separately for each marker after controlling for potential confounders., Results: Between the two arms (33 PLWH each), there was no difference in CD4+ or CD8+ T cells, CD4/CD8 ratio, and IL-6 trajectories. PLWH switching to DTG/3TC had increased levels of both transitional memory and terminally differentiated CD4+ T cells (arm-time interaction p-value = 0.02) and to a lesser extent for the corresponding CD8+ T-cell subsets (p = 0.09). Significantly lower levels of non-classical monocytes were detected in the B/F/TAF arm at T6 (diff = -6.7 cells/mm
3 ; 95% CI; -16, +2.6; p-value for interaction between arm and time = 0.03). All differences were attenuated at T12., Conclusion: No evidence for a difference in absolute CD4+ and CD8+ T-cell counts, CD4/CD8 ratio, and IL-6 trajectories by study arm over 12 months was found. PLWH on DTG/3TC showed higher levels of terminally differentiated and exhausted CD4+ and CD8+ T lymphocytes and non-classical monocytes at T6. Further studies are warranted to better understand the clinical impact of our results., Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT04054089., Competing Interests: GG and CM received a research grant and a speaker honorarium from Gilead, ViiV, MERCK, and Jansen. GG and CM are on the advisory boards of Gilead, ViiV, and MERCK. JM received a speaker honorarium from Gilead and ViiV. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cossarizza, Cozzi-Lepri, Mattioli, Paolini, Neroni, De Biasi, Tartaro, Borella, Fidanza, Gibellini, Beghetto, Roncaglia, Nardini, Milic, Menozzi, Cuomo, Digaetano, Orlando, Borghi, Guaraldi and Mussini.)- Published
- 2023
- Full Text
- View/download PDF
6. Long-term outcome of lamivudine/dolutegravir dual therapy in HIV-infected, virologically suppressed patients.
- Author
-
Maggiolo F, Gulminetti R, Pagnucco L, Digaetano M, Cervo A, Valenti D, Callegaro A, and Mussini C
- Subjects
- Antigens, Surface therapeutic use, Creatinine, Heterocyclic Compounds, 3-Ring adverse effects, Humans, Lamivudine adverse effects, Oxazines, Piperazines, Prospective Studies, Pyridones, RNA, Viral Load, Anti-HIV Agents adverse effects, HIV Infections, HIV-1
- Abstract
Background: The use of DTG-containing two-drug regimens is one of the most promising solutions to the need to ease the management of HIV treatment without harming its efficacy and safety. We report long- term results in patients switched, while virologically suppressed, to the combination of dolutegravir (DTG) plus lamivudine (3TC)., Methods: This is a prospective, clinical, uncontrolled cohort enrolling ART-experienced people living with HIV (PLWH) with HIV-RNA < 50 copies/ml for 6 months or longer, negative hepatitis B virus surface antigen, and without known M184V/I mutations. Kaplan-Meiers curves are used to describe persistency of virological suppression on therapy and a Cox regression model to evaluate baseline characteristics and the risk of stopping therapy., Results: 218 individuals switched their regimen since 2015. The mean estimated follow-up was of 64.3 months (95% CI 61.3-67.3) for approximately 1000 patient/years. After 5 years of follow-up, 77.1% were still on the DTG-3TC combination. No virologic failure was detected throughout the whole study period, and only 15 subjects presented single isolated viral blips above 50 copies/ml. Most patients stopped therapy because of reasons unrelated to study drugs (lost to follow-up; patients' decision; moved to other Centers), but due to the unselected nature of the casuistry; 11 subjects died in the 5 years of follow-up mostly because of pre-existing co-morbidities (6 neoplastic diseases and 2 end-stage liver disease). The median baseline CD4 count was 669 cells/mcl (IQR 483-927). After 5 years it raised to 899 cells/mcl (IQR 646-1160) (P < 0.001) without a significant change of CD8 counts that lowered from 767 cells/mcl (IQR 532-1034) to 683 cells/mcl (IQR 538-988). Consequently, the CD4/CD8 ratio varied from 0.93 (IQR 0.60-1.30) to 1.15 (IQR 0.77-1.45) (P < 0.0001). A non-significant (P = 0.320) increment of mean creatinine, 0.06 mg/dl in magnitude, was observed over the whole follow-up., Conclusion: These long-term results over 5 years reinforce the durability and good tolerability of DTG-3TC. Our results continue to support the recommended switch use of this 2DR as a well-accepted treatment option for ART-experienced PLWH., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
7. Development of post-COVID-19 cardiovascular events: an analysis of clinical features and risk factors from a single hospital retrospective study.
- Author
-
Cuomo G, Puzzolante C, Iadisernia V, Santoro A, Menozzi M, Carli F, Digaetano M, Orlando G, Franceschini E, Bedini A, Meschiari M, Manzini L, Corradi L, Milic J, Borghi V, Brugioni L, Pietrangelo A, Clini E, Girardis M, Guaraldi G, and Mussini C
- Abstract
Cardiovascular complications after a SARS-CoV-2 infection are a phenomenon of relevant scientific interest. The aim of this study was to analyze the onset of post-COVID-19 cardiovascular events in patients hospitalized in a tertiary care center. This is a retrospective study conducted on patients hospitalized over a period of three months. The patients were older than 18 years of age and had a diagnosis of COVID-19 infection confirmed from a nasopharyngeal swab sample. Anamnestic and clinical-laboratory data were collected. Cardiovascular events at 30 days were defined as follows: arrhythmias, myocardial infarction, myocarditis, and pulmonary embolism. Univariate analysis (Student's t-test or Mann-Whitney U test, as appropriate) and multivariate analysis (multinomial logistic regression) were applied to the data. A total of 394 patients were included; they were mostly males and had a median age of 65.5 years. Previous cardiovascular disease was present in 14.7% of patients. Oxygen therapy was required for 77.9%, and 53% received anticoagulant therapy. The overall 30-day mortality was 20.3%. A cardiovascular event developed in 15.7% of the subjects. These were mainly pulmonary embolism (9.4%), followed by arrhythmias (3.3%), myocardial infarction (2.3%), and myocarditis (0.8%). Patients who developed cardiovascular events upon univariate analysis were significantly older, with major comorbidities, a more compromised respiratory situation, and a higher mortality rate. Multivariate analysis revealed independent factors that were significantly associated with the development of cardiovascular events: hypertension, endotracheal intubation, and age older than 75 years. In patients with COVID-19, the development of a cardiovascular event occurs quite frequently and is mainly seen in elderly subjects with comorbidities (especially hypertension) in the presence of a severe respiratory picture., Competing Interests: Competing interests The authors declare that they have no competing interests., (Copyright © 2016 - 2021 InfezMed.)
- Published
- 2021
- Full Text
- View/download PDF
8. Incidence, risk factors and outcome of acute kidney injury (AKI) in patients with COVID-19.
- Author
-
Alfano G, Ferrari A, Fontana F, Mori G, Magistroni R, Meschiari M, Franceschini E, Menozzi M, Cuomo G, Orlando G, Santoro A, Digaetano M, Puzzolante C, Carli F, Bedini A, Milic J, Coloretti I, Raggi P, Mussini C, Girardis M, Cappelli G, and Guaraldi G
- Subjects
- Acute Kidney Injury diagnosis, Acute Kidney Injury mortality, Aged, Aged, 80 and over, COVID-19 diagnosis, COVID-19 mortality, Female, Hematuria epidemiology, Humans, Incidence, Italy epidemiology, Male, Middle Aged, Prognosis, Proteinuria epidemiology, Retrospective Studies, Risk Assessment, Risk Factors, Acute Kidney Injury epidemiology, COVID-19 epidemiology
- Abstract
Background: Acute kidney injury (AKI) is a severe complication of coronavirus disease-2019 (COVID-19). This study aims to evaluate incidence, risk factors and case-fatality rate of AKI in patients with COVID-19., Methods: We reviewed the health medical records of 307 consecutive patients with COVID-19 hospitalized at the University Hospital of Modena, Italy., Results: AKI was diagnosed in 69 out of 307 (22.4%) COVID-19 patients. Stages 1, 2, or 3 AKI accounted for 57.9%, 24.6% and 17.3%, respectively. AKI patients had a mean age of 74.7 ± 9.9 years. These patients showed higher serum levels of the main markers of inflammation and higher rate of severe pneumonia than non-AKI patients. Kidney injury was associated with a higher rate of urinary abnormalities including proteinuria (0.44 ± 0.85 vs 0.18 ± 0.29 mg/mg; P = < 0.0001) and microscopic hematuria (P = 0.032) compared to non-AKI patients. Hemodialysis was performed in 7.2% of the subjects and 33.3% of the survivors did not recover kidney function after AKI. Risk factors for kidney injury were age, male sex, CKD and higher non-renal SOFA score. Patients with AKI had a mortality rate of 56.5%. Adjusted Cox regression analysis revealed that COVID-19-associated AKI was independently associated with in-hospital death (hazard ratio [HR] = 4.82; CI 95%, 1.36-17.08) compared to non-AKI patients., Conclusion: AKI was a common and harmful consequence of COVID-19. It manifested with urinary abnormalities (proteinuria, microscopic hematuria) and conferred an increased risk for death. Given the well-known short-term sequelae of AKI, prevention of kidney injury is imperative in this vulnerable cohort of patients., (© 2021. Japanese Society of Nephrology.)
- Published
- 2021
- Full Text
- View/download PDF
9. AKI in hospitalized patients with COVID-19: a single-center experience.
- Author
-
Alfano G, Giovanella S, Fontana F, Milic J, Ligabue G, Morisi N, Giaroni F, Mori G, Magistroni R, Franceschini E, Bedini A, Cuomo G, DiGaetano M, Meschiari M, Mussini C, Cappelli G, and Guaraldi G
- Subjects
- Hospital Mortality, Humans, Retrospective Studies, SARS-CoV-2, Acute Kidney Injury therapy, COVID-19
- Published
- 2021
10. Herpes Simplex Virus Re-Activation in Patients with SARS-CoV-2 Pneumonia: A Prospective, Observational Study.
- Author
-
Franceschini E, Cozzi-Lepri A, Santoro A, Bacca E, Lancellotti G, Menozzi M, Gennari W, Meschiari M, Bedini A, Orlando G, Puzzolante C, Digaetano M, Milic J, Codeluppi M, Pecorari M, Carli F, Cuomo G, Alfano G, Corradi L, Tonelli R, De Maria N, Busani S, Biagioni E, Coloretti I, Guaraldi G, Sarti M, Luppi M, Clini E, Girardis M, Gyssens IC, and Mussini C
- Abstract
Background: Herpes simplex 1 co-infections in patients with COVID-19 are considered relatively uncommon; some reports on re-activations in patients in intensive-care units were published. The aim of the study was to analyze herpetic re-activations and their clinical manifestations in hospitalized COVID-19 patients, performing HSV-1 PCR on plasma twice a week., Methods: we conducted a prospective, observational, single-center study involving 70 consecutive patients with severe/critical SARS-CoV-2 pneumonia tested for HSV-1 hospitalized at Azienda Ospedaliero-Universitaria of Modena., Results: of these 70 patients, 21 (30.0%) showed detectable viremia and 13 (62%) had clinically relevant manifestations of HSV-1 infection corresponding to 15 events (4 pneumonia, 5 herpes labialis, 3 gingivostomatitis, one encephalitis and two hepatitis). HSV-1 positive patients were more frequently treated with steroids than HSV-1 negative patients (76.2% vs. 49.0%, p = 0.036) and more often underwent mechanical ventilation (IMV) (57.1% vs. 22.4%, p = 0.005). In the unadjusted logistic regression analysis, steroid treatment, IMV, and higher LDH were significantly associated with an increased risk of HSV1 re-activation (odds ratio 3.33, 4.61, and 16.9, respectively). The association with the use of steroids was even stronger after controlling for previous use of both tocilizumab and IMV (OR = 5.13, 95% CI:1.36-19.32, p = 0.016). The effect size was larger when restricting to participants who were treated with high doses of steroids while there was no evidence to support an association with the use of tocilizumab Conclusions: our study shows a high incidence of HSV-1 re-activation both virologically and clinically in patients with SARS-CoV-2 severe pneumonia, especially in those treated with steroids.
- Published
- 2021
- Full Text
- View/download PDF
11. The impact of tocilizumab on respiratory support states transition and clinical outcomes in COVID-19 patients. A Markov model multi-state study.
- Author
-
Milic J, Banchelli F, Meschiari M, Franceschini E, Ciusa G, Gozzi L, Volpi S, Faltoni M, Franceschi G, Iadisernia V, Yaacoub D, Dolci G, Bacca E, Rogati C, Tutone M, Burastero G, Raimondi A, Menozzi M, Cuomo G, Corradi L, Orlando G, Santoro A, Digaetano M, Puzzolante C, Carli F, Bedini A, Busani S, Girardis M, Cossarizza A, Miglio R, Mussini C, Guaraldi G, and D'Amico R
- Subjects
- Aged, Female, Humans, Male, Markov Chains, Middle Aged, Noninvasive Ventilation, Oxygen Inhalation Therapy, Respiration, Artificial, Time Factors, Treatment Outcome, Antibodies, Monoclonal, Humanized therapeutic use, Respiratory Therapy methods, COVID-19 Drug Treatment
- Abstract
Background: The benefit of tocilizumab on mortality and time to recovery in people with severe COVID pneumonia may depend on appropriate timing. The objective was to estimate the impact of tocilizumab administration on switching respiratory support states, mortality and time to recovery., Methods: In an observational study, a continuous-time Markov multi-state model was used to describe the sequence of respiratory support states including: no respiratory support (NRS), oxygen therapy (OT), non-invasive ventilation (NIV) or invasive mechanical ventilation (IMV), OT in recovery, NRS in recovery., Results: Two hundred seventy-one consecutive adult patients were included in the analyses contributing to 695 transitions across states. The prevalence of patients in each respiratory support state was estimated with stack probability plots, comparing people treated with and without tocilizumab since the beginning of the OT state. A positive effect of tocilizumab on the probability of moving from the invasive and non-invasive mechanical NIV/IMV state to the OT in recovery state (HR = 2.6, 95% CI = 1.2-5.2) was observed. Furthermore, a reduced risk of death was observed in patients in NIV/IMV (HR = 0.3, 95% CI = 0.1-0.7) or in OT (HR = 0.1, 95% CI = 0.0-0.8) treated with tocilizumab., Conclusion: To conclude, we were able to show the positive impact of tocilizumab used in different disease stages depicted by respiratory support states. The use of the multi-state Markov model allowed to harmonize the heterogeneous mortality and recovery endpoints and summarize results with stack probability plots. This approach could inform randomized clinical trials regarding tocilizumab, support disease management and hospital decision making., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2021
- Full Text
- View/download PDF
12. Darunavir/Cobicistat Is Associated with Negative Outcomes in HIV-Negative Patients with Severe COVID-19 Pneumonia.
- Author
-
Milic J, Novella A, Meschiari M, Menozzi M, Santoro A, Bedini A, Cuomo G, Franceschini E, Digaetano M, Carli F, Ciusa G, Volpi S, Bacca E, Franceschi G, Yaacoub D, Rogati C, Tutone M, Burastero G, Faltoni M, Iadisernia V, Dolci G, Cossarizza A, Mussini C, Pasina L, and Guaraldi G
- Subjects
- Adult, Anti-HIV Agents adverse effects, COVID-19 mortality, COVID-19 virology, Cobicistat adverse effects, Darunavir adverse effects, Drug Combinations, Female, Humans, Male, Middle Aged, Retrospective Studies, SARS-CoV-2 isolation & purification, Anti-HIV Agents therapeutic use, Cobicistat therapeutic use, Darunavir therapeutic use, COVID-19 Drug Treatment
- Abstract
The aim of this study was to evaluate both positive outcomes, including reduction of respiratory support aid and duration of hospital stay, and negative ones, including mortality and a composite of invasive mechanical ventilation or death, in patients with coronavirus disease 2019 (COVID-19) pneumonia treated with or without oral darunavir/cobicistat (DRV/c, 800/150 mg/day) used in different treatment durations. The secondary objective was to evaluate the percentage of patients treated with DRV/c who were exposed to potentially severe drug-drug interactions (DDIs) and died during hospitalization. This observational retrospective study was conducted in consecutive patients with COVID-19 pneumonia admitted to a tertiary care hospital in Modena, Italy. Kaplan-Meier survival curves and Cox proportional hazards regression were used to compare patients receiving standard of care with or without DRV/c. Adjustment for key confounders was applied. Two hundred seventy-three patients (115 on DRV/c) were included, 75.8% males, mean age was 64.6 (±13.2) years. Clinical improvement was similar between the groups, depicted by respiratory aid switch ( p > .05). The same was observed for duration of hospital stay [13.2 (±8.9) for DRV/c vs. 13.4 (±7.2) days for no-DRV/c, p = .9]. Patients on DRV/c had higher rates of mortality (25.2% vs. 10.1%, p < .0001. The rate of composite outcome of mechanical ventilation and death was higher in the DRV/c group (37.4% vs. 25.3%, p = .03). Multiple serious DDI associated with DRV/c were observed in the 19 patients who died. DRV/c should not be recommended as a treatment option for COVID-19 pneumonia outside clinical trials.
- Published
- 2021
- Full Text
- View/download PDF
13. Efficient T-Cell Compartment in HIV-Positive Patients Receiving Orthotopic Liver Transplant and Immunosuppressive Therapy.
- Author
-
Franceschini E, De Biasi S, Digaetano M, Bianchini E, Lo Tartaro D, Gibellini L, Menozzi M, Zona S, Tarantino G, Nasi M, Codeluppi M, Guaraldi G, Magistri P, Di Benedetto F, Pinti M, Mussini C, and Cossarizza A
- Subjects
- CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, Case-Control Studies, Cross-Sectional Studies, Cytokines metabolism, Female, HIV-1 immunology, Humans, Immunosuppressive Agents, Interferon-gamma, Leukocytes, Mononuclear immunology, Male, Middle Aged, Viral Load, HIV Infections immunology, Immunosuppression Therapy, Liver Transplantation
- Abstract
Background: In patients undergoing orthotopic liver transplant (OLT), immunosuppressive treatment is mandatory and infections are leading causes of morbidity/mortality. Thus, it is essential to understand the functionality of cell-mediated immunity after OLT. The aim of the study was to identify changes in T-cell phenotype and polyfunctionality in human immunodeficiency virus-positive (HIV+) and -negative (HIV-) patients undergoing immunosuppressive treatment after OLT., Methods: We studied peripheral blood mononuclear cells from 108 subjects divided into 4 groups of 27: HIV+ transplanted patients, HIV- transplanted patients, HIV+ nontransplanted patients, and healthy subjects. T-cell activation, differentiation, and cytokine production were analyzed by flow cytometry., Results: Median age was 55 years (interquartile range, 52-59 years); the median CD4 count in HIV+ patients was 567 cells/mL, and all had undetectable viral load. CD4+ and CD8+ T-cell subpopulations showed different distributions between HIV+ and HIV- OLT patients. A cluster representing effector cells expressing PD1 was abundant in HIV- transplanted patients and they were characterized by higher levels of CD4+ T cells able to produce interferon-γ and tumor necrosis factor-α., Conclusions: HIV- transplanted patients have more exhausted or inflammatory T cells compared to HIV+ transplanted patients, suggesting that patients who have already experienced a form of immunosuppression due to HIV infection respond differently to anti-rejection therapy., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
- Published
- 2021
- Full Text
- View/download PDF
14. Immunomodulation for the management of severe SARS-CoV2 infections. State of the art and review of the literature.
- Author
-
Bacca E, Digaetano M, Meschiari M, Franceschini E, Menozzi M, Cuomo G, and Mussini C
- Subjects
- Humans, Immunomodulation, SARS-CoV-2, COVID-19 Drug Treatment
- Abstract
This Mini Review of the literature aimed to assess the role of tocilizumab for the treatment of severe coronavirus disease 2019 (COVID-19). Based on the available scientific evidence, it is not clear to date what is the best therapeutic strategy for the treatment of COVID-19. Since SARS-CoV-2 infection stimulates a vigorous proinflammatory response and may cause the so-called "cytokine storm", immunomodulator drugs have been investigated as potential treatment for severe COVID-19 pneumonia. Among immunomodulators, tocilizumab, a recombinant humanized monoclonal antibody directed against IL-6 receptor, seems to be promising. An increasing number of clinical trials are exploring the role of tocilizumab in COVID-19, focusing on outcomes like mortality, risk of intensive care unit admission and the need for mechanical ventilation. At the moment, there is no conclusive evidence that tocilizumab would be proper outright in all patients with COVID-19 pneumonia, but some studies suggest that its use may be beneficial in selected categories of patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
15. Machine learning in predicting respiratory failure in patients with COVID-19 pneumonia-Challenges, strengths, and opportunities in a global health emergency.
- Author
-
Ferrari D, Milic J, Tonelli R, Ghinelli F, Meschiari M, Volpi S, Faltoni M, Franceschi G, Iadisernia V, Yaacoub D, Ciusa G, Bacca E, Rogati C, Tutone M, Burastero G, Raimondi A, Menozzi M, Franceschini E, Cuomo G, Corradi L, Orlando G, Santoro A, Digaetano M, Puzzolante C, Carli F, Borghi V, Bedini A, Fantini R, Tabbì L, Castaniere I, Busani S, Clini E, Girardis M, Sarti M, Cossarizza A, Mussini C, Mandreoli F, Missier P, and Guaraldi G
- Subjects
- Aged, Betacoronavirus, Blood Gas Analysis, COVID-19, Female, Humans, Italy, Male, Middle Aged, Models, Statistical, Pandemics, Prospective Studies, Respiration, Artificial, Respiratory Insufficiency etiology, SARS-CoV-2, Computer Simulation, Coronavirus Infections complications, Machine Learning, Pneumonia, Viral complications, Respiratory Insufficiency diagnosis
- Abstract
Aims: The aim of this study was to estimate a 48 hour prediction of moderate to severe respiratory failure, requiring mechanical ventilation, in hospitalized patients with COVID-19 pneumonia., Methods: This was an observational prospective study that comprised consecutive patients with COVID-19 pneumonia admitted to hospital from 21 February to 6 April 2020. The patients' medical history, demographic, epidemiologic and clinical data were collected in an electronic patient chart. The dataset was used to train predictive models using an established machine learning framework leveraging a hybrid approach where clinical expertise is applied alongside a data-driven analysis. The study outcome was the onset of moderate to severe respiratory failure defined as PaO2/FiO2 ratio <150 mmHg in at least one of two consecutive arterial blood gas analyses in the following 48 hours. Shapley Additive exPlanations values were used to quantify the positive or negative impact of each variable included in each model on the predicted outcome., Results: A total of 198 patients contributed to generate 1068 usable observations which allowed to build 3 predictive models based respectively on 31-variables signs and symptoms, 39-variables laboratory biomarkers and 91-variables as a composition of the two. A fourth "boosted mixed model" included 20 variables was selected from the model 3, achieved the best predictive performance (AUC = 0.84) without worsening the FN rate. Its clinical performance was applied in a narrative case report as an example., Conclusion: This study developed a machine model with 84% prediction accuracy, which is able to assist clinicians in decision making process and contribute to develop new analytics to improve care at high technology readiness levels., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2020
- Full Text
- View/download PDF
16. Health care during electricity failure: The hidden costs.
- Author
-
Mechtenberg A, McLaughlin B, DiGaetano M, Awodele A, Omeeboh L, Etwalu E, Nanjula L, Musaazi M, and Shrime M
- Subjects
- Bangladesh, Clinical Decision-Making, Cost-Benefit Analysis, Electric Power Supplies classification, Ghana, Humans, Iraq, Uganda, Electric Power Supplies supply & distribution, Health Care Costs
- Abstract
Background: Surgery risks increase when electricity is accessible but unreliable. During unreliable electricity events and without data on increased risk to patients, medical professionals base their decisions on anecdotal experience. Decisions should be made based on a cost-benefit analysis, but no methodology exists to quantify these risks, the associated hidden costs, nor risk charts to compare alternatives., Methods: Two methodologies were created to quantify these hidden costs. In the first methodology through research literature and/or measurements, the authors obtained and analyzed a year's worth of hour-by-hour energy failures for four energy healthcare system (EHS) types in four regions (SolarPV in Iraq, Hydroelectric in Ghana, SolarPV+Wind in Bangladesh, and Grid+Diesel in Uganda). In the second methodology, additional patient risks were calculated according to time and duration of electricity failure and medical procedure impact type. Combining these methodologies, the cost from the Value of Statistical Lives lost divided by Energy shortage ($/kWh) is calculated for EHS type and region specifically. The authors define hidden costs due to electricity failure as VSL/E ($/kWh) and compare this to traditional electricity costs (always defined in $/kWh units), including Levelized Cost of Electricity (LCOE also in $/kWh). This is quantified into a fundamentally new energy healthcare system risk chart (EHS-Risk Chart) based on severity of event (probability of deaths) and likelihood of event (probability of electricity failure)., Results: VSL/E costs were found to be 10 to 10,000 times traditional electricity costs (electric utility or LCOE based). The single power source EHS types have higher risks than hybridized EHS types (especially as power loads increase over time), but all EHS types have additional risks to patients due to electricity failure (between 3 to 105 deaths per 1,000 patients)., Conclusions: These electricity failure risks and hidden healthcare costs can now be calculated and charted to make medical decisions based on a risk chart instead of anecdotal experience. This risk chart connects public health and electricity failure using this adaptable, scalable, and verifiable model., Competing Interests: No authors funded to do this specific research project due to the fact that funding agencies we approached do not fund this type of research connecting electricity and health care directly.
- Published
- 2020
- Full Text
- View/download PDF
17. Short Communication: Circulating Mitochondrial DNA and Lipopolysaccharide-Binding Protein but Not Bacterial DNA Are Increased in Acute Human Immunodeficiency Virus Infection.
- Author
-
Nasi M, Pecorini S, De Biasi S, Digaetano M, Chester J, Aramini B, Lo Tartaro D, Pinti M, De Gaetano A, Gibellini L, Mattioli AV, Mussini C, and Cossarizza A
- Subjects
- Acute-Phase Proteins, Bacterial Translocation, Carrier Proteins, DNA, Bacterial, DNA, Mitochondrial, Humans, Lipopolysaccharide Receptors, Lipopolysaccharides, Membrane Glycoproteins, HIV Infections
- Abstract
Microbial translocation has been suggested as a major driver of chronic immune activation HIV infection. Thus, we compared the extent of microbial translocation in patients with acute HIV infection and patients followed after CD4-guided structured treatment interruption (STI) by measuring different circulating markers: (1) lipopolysaccharide (LPS)-binding protein (LBP), (2) bacterial DNA, (3) soluble CD14 (sCD14), and (4) mitochondrial DNA (mtDNA). Bacterial DNA and sCD14 levels were similar in all groups. Patients in acute phase showed higher levels of LBP and mtDNA. In STI, we found a positive correlation between the percentage of CD8+ T cells and bacterial DNA levels. Considering all patients, LBP was positively correlated with the percentage and the absolute count of CD8+ T cells, and with mtDNA stressing the importance of mitochondrial products in sustaining chronic immune activation.
- Published
- 2020
- Full Text
- View/download PDF
18. Epidemiology and Risk Factors Associated With Mortality in Consecutive Patients With Bacterial Bloodstream Infection: Impact of MDR and XDR Bacteria.
- Author
-
Santoro A, Franceschini E, Meschiari M, Menozzi M, Zona S, Venturelli C, Digaetano M, Rogati C, Guaraldi G, Paul M, Gyssens IC, and Mussini C
- Abstract
Background: Mortality related to bloodstream infections (BSIs) is high. The epidemiology of BSIs is changing due to the increase in multidrug resistance, and it is unclear whether the presence of multidrug-resistant (MDR) organisms, per se, is an independent risk factor for mortality. Our objectives were, first, to describe the epidemiology and outcome of BSIs and, second, to determine the risk factors associated with mortality among patients with BSI., Methods: This research used a single-center retrospective observational study design. Patients were identified through microbiological reports. Data on medical history, clinical condition, bacteria, antimicrobial therapy, and mortality were collected. The primary outcome was crude mortality at 30 days. The relationships between mortality and demographic, clinical, and microbiological variables were analyzed by multivariate analysis., Results: A total of 1049 inpatients were included. MDR bacteria were isolated in 27.83% of patients, where 2.14% corresponded to an extremely drug-resistant (XDR) isolate. The crude mortality rates at days 7, 30, and 90 were 12.11%, 25.17%, and 36.13%, respectively. Pitt score >2, lung and abdomen as site of infection, and XDR Pseudomonas aeruginosa were independent risk factors for 7-, 30-, and 90-day mortality. Charlson score >4, carbapenem-resistant Klebsiella pneumoniae , and XDR Acinetobacter baumannii were independent risk factors for 30- and 90-day mortality. Infection by XDR gram-negative bacteria, Charlson score >4, and immunosuppression were independent risk factors for mortality in patients who were stable at the time of BSI., Conclusions: BSI is an event with an extreme impact on mortality. Patients with severe clinical condition are at higher risk of death. The presence of XDR gram-negative bacteria in blood is strongly and independently associated with patient death., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
- Published
- 2020
- Full Text
- View/download PDF
19. Epidemiology and Outcomes of Bloodstream Infections in HIV-Patients during a 13-Year Period.
- Author
-
Franceschini E, Santoro A, Menozzi M, Bacca E, Venturelli C, Zona S, Bedini A, Digaetano M, Puzzolante C, Meschiari M, Cuomo G, Orlando G, Sarti M, Guaraldi G, Cozzi-Lepri A, and Mussini C
- Abstract
No data on antibiotic resistance in bloodstream infection (BSI) in people living with HIV (PLWH) exist. The objective of this study was to describe BSI epidemiology in PLWH focusing on multidrug resistant (MDR) organisms. A retrospective, single-center, observational study was conducted including all positive blood isolates in PLWH from 2004 to 2017. Univariable and multivariable GEE models using binomial distribution family were created to evaluate the association between MDR and mortality risk. In total, 263 episodes (299 isolates) from 164 patients were analyzed; 126 (48%) BSI were community-acquired, 137 (52%) hospital-acquired. At diagnosis, 34.7% of the patients had virological failure, median CD4 count was 207/μL. Thirty- and 90-day mortality rates were 24.2% and 32.4%, respectively. Thirty- and 90-day mortality rates for MDR isolates were 33.3% and 46.9%, respectively ( p < 0.05). Enterobacteriaceae were the most prevalent microorganisms (29.8%), followed by Coagulase-negative staphylococci (21.4%), and S. aureus (12.7%). In BSI due to MDR organisms, carbapenem-resistant K. pneumoniae and methicillin-resistant S. aureus were associated with mortality after adjustment for age, although this correlation was not confirmed after further adjustment for CD4 < 200/μL. In conclusion, BSI in PLWH is still a major problem in the combination antiretroviral treatment era and it is related to a poor viro-immunological status, posing the question of whether it should be considered as an AIDS-defining event.
- Published
- 2020
- Full Text
- View/download PDF
20. Acute myocarditis as the main clinical manifestation of SARS-CoV 2 infection.
- Author
-
Cuomo G, Menozzi M, Carli F, Digaetano M, Raimondi A, Reggianini L, Ligabue G, Guaraldi G, and Mussini C
- Abstract
We describe a case of acute myocarditis, which was reported as the main COVID-19 clinical manifestation, with a favorabile outcome. In addition to symptoms, laboratory tests (BNP and troponin), echocardiogram and cardiac MRI contributed to diagnosis. Regardless heart biopsy was not obtained, it is likely an immunological pathogenesis of this condition which pave the way to further therapeutic implications, since there are currently no standardized treatments., Competing Interests: Conflict of interest: The authors declare no conflict of interest., (©Copyright: the Author(s).)
- Published
- 2020
- Full Text
- View/download PDF
21. Altered Expression of PYCARD, Interleukin 1β, Interleukin 18, and NAIP in Successfully Treated HIV-Positive Patients With a Low Ratio of CD4+ to CD8+ T Cells.
- Author
-
Nasi M, Pecorini S, De Biasi S, Bianchini E, Digaetano M, Neroni A, Lo Tartaro D, Pullano R, Pinti M, Gibellini L, Mussini C, and Cossarizza A
- Subjects
- Adult, Aged, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, Female, Gene Expression Regulation, HIV Infections virology, HIV Seropositivity, Humans, Male, Middle Aged, Monocytes immunology, CARD Signaling Adaptor Proteins genetics, HIV Infections immunology, Inflammasomes immunology, Interleukin-18 genetics, Interleukin-1beta genetics, Neuronal Apoptosis-Inhibitory Protein genetics
- Abstract
The expression and activity of main inflammasome components in monocytes from successfully treated human immunodeficiency virus (HIV)-positive patients are poorly studied. Thus, we enrolled 18 patients with a low and 17 with a normal ratio of CD4+ T cells to CD8+ T cells and 11 healthy donors. We found that patients with a low ratio had decreased CCR2 expression among classical and intermediate monocytes and increased CCR5 expression among classical monocytes, compared with patients with a normal ratio. Patients with a low ratio also had higher NAIP and PYCARD messenger RNA levels after lipopolysaccharide stimulation, suggesting an altered ability to control immune activation that could affect their immune reconstitution., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
- Published
- 2019
- Full Text
- View/download PDF
22. Ceftolozane/tazobactam for the treatment of serious Pseudomonas aeruginosa infections: a multicentre nationwide clinical experience.
- Author
-
Bassetti M, Castaldo N, Cattelan A, Mussini C, Righi E, Tascini C, Menichetti F, Mastroianni CM, Tumbarello M, Grossi P, Artioli S, Carannante N, Cipriani L, Coletto D, Russo A, Digaetano M, Losito AR, Peghin M, Capone A, Nicolè S, and Vena A
- Subjects
- Aged, Bacteremia drug therapy, Bacteremia microbiology, Bone Diseases, Infectious drug therapy, Bone Diseases, Infectious microbiology, Drug Resistance, Multiple, Bacterial genetics, Female, Humans, Male, Middle Aged, Pneumonia, Bacterial drug therapy, Pneumonia, Bacterial microbiology, Pneumonia, Ventilator-Associated drug therapy, Pneumonia, Ventilator-Associated microbiology, Pseudomonas Infections microbiology, Pseudomonas aeruginosa genetics, Pseudomonas aeruginosa isolation & purification, Retrospective Studies, Skin Diseases, Bacterial drug therapy, Skin Diseases, Bacterial microbiology, Treatment Outcome, Urinary Tract Infections drug therapy, Urinary Tract Infections microbiology, Anti-Bacterial Agents therapeutic use, Cephalosporins adverse effects, Cephalosporins therapeutic use, Pseudomonas Infections drug therapy, Pseudomonas aeruginosa drug effects, Tazobactam adverse effects, Tazobactam therapeutic use
- Abstract
This study describes the largest clinical experience using ceftolozane/tazobactam (C/T) for different Pseudomonas aeruginosa infections. A retrospective study was performed at 22 hospitals in Italy (June 2016-March 2018). All adult patients treated with ≥4 days of C/T were enrolled. Successful clinical outcome was defined as complete resolution of clinical signs/symptoms related to P. aeruginosa infection and lack of microbiological evidence of infection. C/T treatment was documented in 101 patients with diverse infections, including nosocomial pneumonia (31.7%), acute bacterial skin and skin-structure infection (20.8%), complicated UTI (13.9%), complicated IAI (12.9%), bone infection (8.9%) and primary bacteraemia (5.9%). Over one-half of P. aeruginosa strains were XDR (50.5%), with 78.2% of isolates resistant to at least one carbapenem. C/T was used as first-line therapy in 39 patients (38.6%). When used as second-line or later, the most common reasons for discontinuation of previous antibiotics were in vitro resistance of P. aeruginosa and clinical failure of previous therapy. Concomitant antibiotics were reported in 35.6% of patients. C/T doses were 1.5 g q8h in 70 patients (69.3%) and 3 g q8h in 31 patients (30.7%); median duration of C/T therapy was 14 days. Overall clinical success was 83.2%. Significant lower success rates were observed in patients with sepsis or receiving continuous renal replacement therapy (CRRT). Mild adverse events were reported in only three patients. C/T demonstrated a favourable safety and tolerability profile regardless of the infection type. Clinicians should be aware of the risk of clinical failure with C/T therapy in septic patients receiving CRRT., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
23. Migration and health: A retrospective study about the prevalence of HBV, HIV, HCV, tuberculosis and syphilis infections amongst newly arrived migrants screened at the Infectious Diseases Unit of Modena, Italy.
- Author
-
Cuomo G, Franconi I, Riva N, Bianchi A, Digaetano M, Santoro A, Codeluppi M, Bedini A, Guaraldi G, and Mussini C
- Subjects
- Adolescent, Adult, Cross-Sectional Studies, Female, Humans, Italy epidemiology, Male, Prevalence, Radiography, Thoracic, Retrospective Studies, Serologic Tests, Tuberculin Test, Young Adult, HIV Infections epidemiology, Hepatitis B epidemiology, Hepatitis C epidemiology, Syphilis epidemiology, Transients and Migrants, Tuberculosis epidemiology
- Abstract
Introduction: Aim of the study is to evaluate the prevalence of HBV, HIV, HCV, tuberculosis and syphilis infection among immigrants assigned to the immigrant centre of the province of Modena., Methods: At the time of arrival all immigrant were tested for: HBsAg, HBsAb, HBcAb, Ag p24/HIVAb, HCVAb, RPR, TPPA, Mantoux test (>10mm diameter of induration was considered to be positive), Chest X-rays. In case of positive samples, second level tests were performed (HbeAg, HBeAb, HDVAb, and baseline management and treatment of the infection detected)., Results: A total of 304 immigrant people were enrolled in the study. HBsAg positivity was 12.2%, HCVAb 3.3%, HIVAb 1.6%, TPPA+RPR positivity in the 0.7%; 10.2% had a positive Mantoux test; 5.6% had Chest X-rays positive for signs of infection and 6 patients had an active tuberculosis. 83.8% HBsAg were HBeAb positive/HBeAg negative. HDVAb resulted positive in 1 patient (2.7%). Previous HBV infection was detected in 28.6% of cases, isolated HBcAb in 2.3%; 5.6% of patients resulted to be positive to HbsAb alone (probable vaccinated)., Conclusion: Our study confirms the high prevalence of HBsAg positivity and latent tuberculosis among immigrants, underlying the importance of screening for infections in this special population., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
24. Efficacy of Ceftazidime-Avibactam Salvage Therapy in Patients With Infections Caused by Klebsiella pneumoniae Carbapenemase-producing K. pneumoniae.
- Author
-
Tumbarello M, Trecarichi EM, Corona A, De Rosa FG, Bassetti M, Mussini C, Menichetti F, Viscoli C, Campoli C, Venditti M, De Gasperi A, Mularoni A, Tascini C, Parruti G, Pallotto C, Sica S, Concia E, Cultrera R, De Pascale G, Capone A, Antinori S, Corcione S, Righi E, Losito AR, Digaetano M, Amadori F, Giacobbe DR, Ceccarelli G, Mazza E, Raffaelli F, Spanu T, Cauda R, and Viale P
- Subjects
- Adult, Aged, Drug Combinations, Female, Humans, Italy, Klebsiella Infections microbiology, Klebsiella Infections mortality, Klebsiella Infections pathology, Male, Middle Aged, Retrospective Studies, Survival Analysis, Treatment Outcome, Anti-Bacterial Agents therapeutic use, Azabicyclo Compounds therapeutic use, Carbapenem-Resistant Enterobacteriaceae isolation & purification, Ceftazidime therapeutic use, Klebsiella Infections drug therapy, Klebsiella pneumoniae isolation & purification, Salvage Therapy methods, beta-Lactamase Inhibitors therapeutic use
- Abstract
Background: Ceftazidime-avibactam (CAZ-AVI) has been approved in Europe for the treatment of complicated intra-abdominal and urinary tract infections, as well as hospital-acquired pneumonia, and for gram-negative infections with limited treatment options. CAZ-AVI displays in vitro activity against Klebsiella pneumoniae carbapenemase (KPC) enzyme producers, but clinical trial data on its efficacy in this setting are lacking., Methods: We retrospectively reviewed 138 cases of infections caused by KPC-producing K. pneumoniae (KPC-Kp) in adults who received CAZ-AVI in compassionate-use programs in Italy. Case features and outcomes were analyzed, and survival was then specifically explored in the large subcohort whose infections were bacteremic., Results: The 138 patients started CAZ-AVI salvage therapy after a first-line treatment (median, 7 days) with other antimicrobials. CAZ-AVI was administered with at least 1 other active antibiotic in 109 (78.9%) cases. Thirty days after infection onset, 47 (34.1%) of the 138 patients had died. Thirty-day mortality among the 104 patients with bacteremic KPC-Kp infections was significantly lower than that of a matched cohort whose KPC-Kp bacteremia had been treated with drugs other than CAZ-AVI (36.5% vs 55.8%, P = .005). Multivariate analysis of the 208 cases of KPC-Kp bacteremia identified septic shock, neutropenia, Charlson comorbidity index ≥3, and recent mechanical ventilation as independent predictors of mortality, whereas receipt of CAZ-AVI was the sole independent predictor of survival., Conclusions: CAZ-AVI appears to be a promising drug for treatment of severe KPC-Kp infections, especially those involving bacteremia.
- Published
- 2019
- Full Text
- View/download PDF
25. Incidence of HCV infection amongst HIV positive men who had sex with men and prevalence data from patients followed at the Infectious Diseases Clinic of Modena, Italy.
- Author
-
Cuomo G, Digaetano M, Menozzi M, Tagliazucchi S, Guaraldi G, Borghi V, and Mussini C
- Subjects
- Adult, Aged, Coinfection virology, Hepatitis C Antibodies blood, Humans, Incidence, Italy epidemiology, Kaplan-Meier Estimate, Male, Middle Aged, Prevalence, Young Adult, Coinfection epidemiology, HIV Infections complications, Hepatitis C epidemiology, Homosexuality, Male statistics & numerical data
- Abstract
Background: Men who had sex with men (MSM) living with HIV are at higher risk of developing sexual transmitted diseases. This study reports two years incidence rate and prevalence of HCV in a cohort of HIV positive MSM., Methods: MSM HIV-positive outpatients negative to HCV-Ab at first observation entered a Kaplan-Meier model in order to assess the HCV infection incidence rate. Prevalence analysis was performed with MSM HIV-positive that were on follow-up at 2016. An MSM population HIV-negative served as control., Results: 421 patients entered the incidence analysis. The incidence rate of HCV infection among MSM-HIV people was 0.44 per 100 patients-years (19 events). 40 out of 442 (9%) patients were HCV-positive (prevalence analysis); they were mostly genotype 1a and 3 with APRI score <0.7 (87.5%). Univariate analysis between MSM HIV-positive patients and MSM HIV-negative showed significant differences in the prevalence rate (9.0% vs 0.6%, P < 0.001) and median age (39 vs 47, P < 0.001)., Conclusion: Incidence and prevalence rate of HCV amongst MSM HIV-positive patients is higher than in other settings. Annual HCV-Ab screening for MSM HIV-positive patients should be enforced and early treatment of HCV recommended., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
26. Exploring viral reservoir: The combining approach of cell sorting and droplet digital PCR.
- Author
-
Gibellini L, Pecorini S, De Biasi S, Pinti M, Bianchini E, De Gaetano A, Digaetano M, Pullano R, Lo Tartaro D, Iannone A, Mussini C, Cossarizza A, and Nasi M
- Subjects
- Antiretroviral Therapy, Highly Active, Cell Separation methods, DNA, Viral genetics, DNA, Viral isolation & purification, HIV Infections drug therapy, HIV Infections immunology, HIV-1 isolation & purification, HIV-1 pathogenicity, Humans, RNA, Viral genetics, RNA, Viral isolation & purification, Flow Cytometry methods, HIV Infections virology, Polymerase Chain Reaction methods, Virus Replication genetics
- Abstract
Combined antiretroviral therapy (cART) blocks different steps of HIV replication and maintains plasma viral RNA at undetectable levels. The virus can remain in long-living cells and create a reservoir where HIV can restart replicating after cART discontinuation. A persistent viral production triggers and maintains a persistent immune activation, which is a well-known feature of chronic HIV infection, and contributes either to precocious aging, or to the increased incidence of morbidity and mortality of HIV positive patients. The new frontier of the treatment of HIV infection is nowadays eradication of the virus from all host cells and tissues. For this reason, it is crucial to have a clear and precise idea of where the virus hides, and which are the cells that keep it silent. Important efforts have been made to improve the detection of viral reservoirs, and new techniques are now giving the opportunity to characterize viral reservoirs. Among these techniques, a strategic approach based upon cell sorting and droplet digital PCR (ddPCR) is opening new horizons and opportunities of research. This review provides an overview of the methods that combine cell sorting and ddPCR for the quantification of HIV DNA in different cell types, and for the detection of its maintenance., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
27. Clinical Utility of Epstein-Barr Virus Viral Load Monitoring and Risk Factors for Posttransplant Lymphoproliferative Disorders After Kidney Transplantation: A Single-Center, 10-Year Observational Cohort Study.
- Author
-
Franceschini E, Plessi J, Zona S, Santoro A, Digaetano M, Fontana F, Alfano G, Guaraldi G, Comoli P, Facchini F, Potenza L, Gennari W, Codeluppi M, Luppi M, Cappelli G, Gyssens IC, and Mussini C
- Abstract
Background: Posttransplant lymphoproliferative disease (PTLD) is an important cause of morbidity and mortality in solid organ transplants. Epstein Barr virus (EBV) plays a major role in PTLD development. Guidelines recommend EBV viral load (VL) monitoring in high-risk populations in the first year., Methods: Retrospective observational study in all adult patients who had at least 1 EBV-VL performed in the postkidney transplant (KT) period from January 2005 to December 2014 at the Policlinico Modena Hospital. We compared patients with negative EBV-DNA to patients with positive EBV-DNA and we described PTLD developed in the study period., Results: One hundred ninety (36.3%) KT patients of 523 were screened for EBV-DNA with 796 samples. One hundred twenty-eight (67.4%) of 190 tested patients presented at least 1 positive sample for EBV. Older age, the use of sirolimus, everolimus, and steroids were associated with EBV-DNA positivity in the univariate analysis. Nine (1.7%) of 523 patients had PTLD. Incidence rate of PTLD in the KT cohort was 0.19/100 person year follow-up (95% confidence interval, 0.09-0.37). One of 9 patients developed early PTLD and was a high-risk patient. Only this PTLD case was positive for EBV. No PTLD case had an EBV-VL superior to 4000 copies/mL., Conclusions: Our results suggest that the keystone of PTLD diagnosis is the clinical suspicion. Our study suggests that, in line with guidelines, EBV-VL assays may be avoided in low-risk patients in the absence of a strong clinical PTLD suspicion without increasing patients' risk of developing PTLD. This represents a safe and cost-saving clinical strategy for our center., Competing Interests: The authors declare no funding or conflict of interest.
- Published
- 2017
- Full Text
- View/download PDF
28. HIV-DNA content in different CD4+ T-cell subsets correlates with CD4+ cell : CD8+ cell ratio or length of efficient treatment.
- Author
-
Gibellini L, Pecorini S, De Biasi S, Bianchini E, Digaetano M, Pinti M, Carnevale G, Borghi V, Guaraldi G, Mussini C, Cossarizza A, and Nasi M
- Subjects
- Adult, Female, Humans, Male, Middle Aged, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets virology, CD4-CD8 Ratio, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes virology, CD8-Positive T-Lymphocytes immunology, DNA, Viral analysis, HIV Infections immunology, HIV Infections virology
- Abstract
Objectives: HIV establishes a latent infection at different degrees within naïve (TN) or central (TCM) and effector memory (TEM) CD4 T cell. Studying patients in whom HIV production was suppressed by combined antiretroviral therapy, our main aim was to find which factors are related or can influence intracellular viral reservoir in different CD4 T-cell subsets., Methods: We enrolled 32 HIV patients successfully treated for more than 2 years, with a CD4 T-cell count more than 500 cells/μl and plasma viremia undetectable from at least 1 year. Proviral HIV-DNA, the amount of cells expressing signal-joint T-cell receptor rearrangement excision circles and telomere length were quantified by droplet digital PCR in highly purified, sorted CD4 T-cell subsets; plasma IL-7 and IL-15 were measured by ELISA., Results: HIV-DNA was significantly lower in TN cells compared with TCM or to TEM. Conversely, TN cells contained more signal-joint T-cell receptor rearrangement excision circles compared with TCM or to TEM; no appreciable changes were observed in telomere length. HIV-DNA content was significantly higher in TN and TCM cells, but not in TEM, from patients with shorter time of treatment, or in those with lower CD4 : CD8 ratio., Conclusion: Length of treatment or recovery of CD4 : CD8 ratio significantly influences viral reservoir in both TN and TCM. Measuring HIV-DNA in purified lymphocyte populations allows a better monitoring of HIV reservoir and could be useful for designing future eradication strategies.
- Published
- 2017
- Full Text
- View/download PDF
29. Lamivudine/dolutegravir dual therapy in HIV-infected, virologically suppressed patients.
- Author
-
Maggiolo F, Gulminetti R, Pagnucco L, Digaetano M, Benatti S, Valenti D, Callegaro A, Ripamonti D, and Mussini C
- Subjects
- CD4 Lymphocyte Count, Comorbidity, Drug Therapy, Combination, Female, HIV Infections immunology, HIV Infections physiopathology, Humans, Male, Middle Aged, Oxazines, Piperazines, Prospective Studies, Pyridones, RNA, Viral blood, Treatment Outcome, HIV Infections drug therapy, HIV Infections virology, HIV-1 drug effects, Heterocyclic Compounds, 3-Ring therapeutic use, Lamivudine therapeutic use, Viral Load drug effects
- Abstract
Background: Little is known about the applicability of dual treatments based on integrase inhibitors. We explored the combination of lamivudine + dolutegravir as an option when switching from standard cART in virologically suppressed patients., Methods: In this prospective cohort we enrolled patients previously switched to 3TC + DTG who were 18 years or older, with no previous resistance mutations to the used drugs, having a HIV-RNA <50 copies/ml for 6 months or longer, negative for HBsAg and on a stable (>6 months) cART., Results: Ninety-four individuals were included. They were mostly men (77.7%) with a mean age of 53 years. They presented 159 co-morbidities including cardiovascular, bone, hepatic, kidney, and CNS diseases. Because of these pathologies, they took 207 non-ARV drugs (mean 2.2 per patient). Median duration of viral suppression was 77.5 months (IQR 61). All subjects were prospectively followed up to week 24 and all remained on dual therapy during the whole period. Neither virological failure, nor viral blip was detected. The median CD4 count rose from 658 cells/mcl (IQR 403) to 724 cells/mcl (IQR 401) (P = 0.006) without a significant (P = 0.44) change in the CD4/CD8 ratio. A significant (P < 0.0001) increment of median creatinine from 0.87 mg/dl (IQR 0.34) to 0.95 mg/dl (IQR 0.29) was observed in the first 2 months but thereafter leveled on these values (1.00 mg/dl; IQR 0.35) (P = 0.111 compared to 2 months). The lipid profile slightly improved. The daily cost of cART was significantly (P < 0.0001) reduced of 6.89 euros (SD 6.10)., Discussion: Switching to a dual cART regimen based on lamivudine + dolutegravir maintains virological efficacy up to week 24, and is associated to slight improvements of the immunologic and metabolic status. The strategy allows to freely using concomitant medications for associated pathologies. The dual therapy is less expensive in economic terms., Conclusion: Although still limited evidence exists, a dolutegravir-based dual therapy in combination with lamivudine shows promising results to be confirmed in larger controlled trials.
- Published
- 2017
- Full Text
- View/download PDF
30. Th1 and Th17 proinflammatory profile characterizes invariant natural killer T cells in virologically suppressed HIV+ patients with low CD4+/CD8+ ratio.
- Author
-
De Biasi S, Bianchini E, Nasi M, Digaetano M, Gibellini L, Carnevale G, Borghi V, Guaraldi G, Pinti M, Mussini C, and Cossarizza A
- Subjects
- Adult, Anti-Retroviral Agents therapeutic use, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, Female, Flow Cytometry, Humans, Male, Middle Aged, Sustained Virologic Response, CD4-CD8 Ratio, HIV Infections pathology, Natural Killer T-Cells immunology, Th1 Cells immunology, Th17 Cells immunology
- Abstract
Introduction: Scanty data exist on the phenotype and functionality of invariant natural killer T (iNKT) cells in HIV-infected (HIV+) patients., Methods: By flow cytometry, we studied iNKT cells from 54 HIV+ patients who started combined antiretroviral therapy and had undetectable viral load for more than 1 year. Twenty-five maintained a CD4/CD8 ratio less than 0.4, whereas 29 reached a ratio more than 1.1; 32 age-matched and sex-matched patients were healthy controls (CTR)., Results: Patients with low ratio had lower percentage of CD4 iNKT cells compared with patients with high ratio and higher CD8 iNKT cell percentage; double-negative iNKT cells were lower in HIV+ patients compared with CTR. Patients with low ratio had higher percentage of CD4 and double-negative iNKT cells expressing CD38 and HLA-DR compared with patients with high ratio. CD4 iNKT cells expressing PD-1 were higher in patients with CD4/CD8 ratio less than 0.4, whereas double-negative iNKT cells expressing PD-1 were lower compared with patients with ratio more than 1.1. Patients with low ratio had higher CD4 iNKT cells producing IL-17, CD8 iNKT cells producing IFN-γ, TNF-α or IFN-γ and TNF-α, and double-negative iNKT cells producing IL-17 or IL-17 and IFN-γ compared with CTR. Activated CD4 (or CD8) T cells correlated with activated CD4 (or CD8) iNKT cells, as well as the percentages of CD4 (or CD8) T cells expressing PD-1 was correlated to that of CD4 (or CD8) iNKT cells expressing PD-1., Conclusion: Low CD4/CD8 ratio despite effective combined antiretroviral therapy is associated with altered iNKT cell subsets, enhanced activation, and prominent Th1/Th17 proinflammatory profile.
- Published
- 2016
- Full Text
- View/download PDF
31. Analysis of inflammasomes and antiviral sensing components reveals decreased expression of NLRX1 in HIV-positive patients assuming efficient antiretroviral therapy.
- Author
-
Nasi M, De Biasi S, Bianchini E, Digaetano M, Pinti M, Gibellini L, Pecorini S, Carnevale G, Guaraldi G, Borghi V, Mussini C, and Cossarizza A
- Subjects
- Adult, Female, Gene Expression Profiling, Humans, Immunity, Innate, Leukocytes, Mononuclear immunology, Male, Middle Aged, Real-Time Polymerase Chain Reaction, Anti-Retroviral Agents administration & dosage, HIV Infections drug therapy, HIV Infections pathology, Inflammasomes analysis, Mitochondrial Proteins analysis, Receptors, Immunologic analysis
- Abstract
Objective: Few studies have investigated the importance of different components of the inflammasome system and of innate mitochondrial sensing (IMS) pathways in HIV infection and its treatment. We analysed the expression of several components of the inflammasome and of the IMS in HIV-positive patients taking successful combination antiretroviral therapy (cART)., Methods: We enrolled 20 HIV-positive patients under cART, who achieved viral suppression since at least 10 months and 20 age and sex-matched healthy donors. By RT-PCR, using peripheral blood mononuclear cells (PBMCs), we quantified the mRNA expression of 16 genes involved in inflammasome activation and regulation (AIM2, NAIP, PYCARD, CASP1, CASP5, NLRP6, NLRP1, NLRP3, TXNIP, BCL2, NLRC4, PANX1, P2RX7, IL-18, IL-1β, SUGT1) and eight genes involved in IMS (MFN2, MFN1, cGAS, RIG-I, MAVS, NLRX1, RAB32, STING)., Results: Compared with controls, HIV-positive patients showed significantly lower mRNA levels of the mitochondrial protein NLRX1, which plays a key role in regulating apoptotic cell death; main PBMC subpopulations behave in a similar manner. No differences were observed in the expression of inflammasome components, which however showed complex correlations., Conclusion: The decreased level of NLRX1 in HIV infection could suggest that the virus is able to downregulate mechanisms linked to triggering of cell death in several immune cell types. The fact that HIV-positive patients did not show altered expression of inflammasome components, nor of most genes involved in IMS, suggests that the infection and/or the chronic immune activation does not influence the transcriptional machinery of innate mechanisms able to trigger inflammation at different levels.
- Published
- 2015
- Full Text
- View/download PDF
32. Vibrio vulnificus corneal ulcer. Case reports.
- Author
-
DiGaetano M, Ball SF, and Straus JG
- Subjects
- Adult, Anti-Bacterial Agents administration & dosage, Corneal Ulcer drug therapy, Corneal Ulcer surgery, Humans, Male, Ointments, Ophthalmic Solutions, Vibrio isolation & purification, Corneal Ulcer etiology, Vibrio Infections drug therapy, Vibrio Infections surgery
- Published
- 1989
- Full Text
- View/download PDF
33. The pathogenesis of contact lens-associated Pseudomonas aeruginosa corneal ulceration. II. An animal model.
- Author
-
DiGaetano M, Stern GA, and Zam ZS
- Subjects
- Animals, Bacterial Adhesion drug effects, Cornea microbiology, Corneal Injuries, Disease Models, Animal, Epithelium injuries, Epithelium microbiology, Mucins pharmacology, Pseudomonas aeruginosa metabolism, Rabbits, Contact Lenses, Hydrophilic adverse effects, Corneal Ulcer microbiology, Eye Infections, Bacterial etiology, Pseudomonas Infections etiology
- Published
- 1986
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.