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1. Multi-Criteria Decision Analysis to prioritize hospital admission of patients affected by COVID-19 in low-resource settings with hospital-bed shortage

Author: Durante Mangoni, E., Florio, L.L., Zampino, R., Mele, F., Gentile, I., Pinchera, B., Coppola, N., Pisaturo, M., Luzzati, R., Petrosillo, N., Nicastri, E., Corpolongo, A., Cataldo, M.A., D’Abramo, A., Maffongelli, G., Scorzolini, L., Palazzolo, C., Boumis, E., Pan, A., D’Arminio Monforte, A., Bai, F., Antinori, S., De Rosa, F.G., Corcione, S., Lupia, T., Pinna, S.M., Scabini, S., Canta, F., Belloro, S., Bisoffi, Z., Angheben, A., Gobbi, F., Turcato, E., Ronzoni, N., Moro, L., Calabria, S., Rodari, P., Bertoli, G., Marasca, G., Puoti, M., Gori, A., Bandera, A., Mangioni, D., Rizzi, M., Castelli, F., Montineri, A., Coco, C.A., Maresca, M., Frasca, M., Aquilini, D., Vincenzi, M., Lambertenghi, L., De Rui, M.E., Razzaboni, E., Cattaneo, P., Visentin, A., Erbogasto, A., Dalla Vecchia, I., Coledan, I., Vecchi, M., Be, G., Motta, L., Zaffagnini, A., Auerbach, N., Del Bravo, P., Azzini, A.M., Righi, E., Carrara, E., Savoldi, A., Sibani, M., Lattuada, E., Carolo, G., Cordioli, M., Soldani, F., Pezzani, M.D., Avallone, S., Bruno, R., Ricciardi, A., Saggese, M.P., Malerba, G., De Nardo, Pasquale, Gentilotti, Elisa, Mazzaferri, Fulvia, Cremonini, Eleonora, Hansen, Paul, Goossens, Herman, and Tacconelli, Evelina
Published: 2020
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2. (718) Multiorgan Donor Bronchoalveolar Lavage Positivity: Incidence, Risk Factors, and Lung Transplant Recipients’ Outcome

Author: Fumagalli, J., primary, Rosso, L., additional, Cattaneo, M., additional, Romeo, G., additional, Scaravilli, V., additional, Righi, I., additional, Damarco, F., additional, Mangioni, D., additional, Gori, F., additional, Bandera, A., additional, Rossetti, V., additional, Morlacchi, L., additional, Nosotti, M., additional, Zanella, A., additional, and Grasselli, G., additional
Published: 2023
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3. Characteristics of 1573 healthcare workers who underwent nasopharyngeal swab testing for SARS-CoV-2 in Milan, Lombardy, Italy

Author: Lombardi, A., Consonni, D., Carugno, M., Bozzi, G., Mangioni, D., Muscatello, A., Castelli, V., Palomba, E., Cantù, A.P., Ceriotti, F., Tiso, B., Pesatori, A.C., Riboldi, L., Bandera, A., Lunghi, G., and Gori, A.
Published: 2020
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4. Clinical factors associated with death in 3044 COVID-19 patients managed in internal medicine wards in Italy: comment

Author: Bandera, A., Nobili, A., Tettamanti, M., Harari, S., Bosari, S., Mannucci, P. M., Scudeller, L., Fusetti, G., Rusconi, L., Dell'Orto, S., Prati, D., Valenti, L., Giovannelli, S., Manunta, M., Lamorte, G., Ferrari, F., Gori, A., Muscatello, A., Mangioni, D., Alagna, L., Bozzi, G., Lombardi, A., Ungaro, R., Ancona, G., Zuglian, G., Bolis, M., Iannotti, N., Ludovisi, S., Comelli, A., Renisi, G., Biscarini, S., Castelli, V., Palomba, E., Fava, M., Fortina, V., Peri, C. A., Saltini, P., Viero, G., Itri, T., Ferroni, V., Pastore, V., Massafra, R., Liparoti, A., Muheberimana, T., Giommi, A., Bianco, R., De Azevedo, R. M., Chitani, G. E., Peyvandi, F., Gualtierotti, R., Ferrari, B., Rossio, R., Boasi, N., Pagliaro, E., Massimo, C., De Caro, M., Montano, N., Vigone, B., Bellocchi, C., Carandina, A., Fiorelli, E., Melli, V., Tobaldini, E., Blasi, F., Aliberti, S., Spotti, M., Terranova, L., Misuraca, S., D'Adda, A., Della Fiore, S., Di Pasquale, M., Contarini, M. M. M., Ori, M., Morlacchi, L., Rossetti, V., Gramegna, A., Pappalettera, M., Cavallini, M., Buscemi, A., Vicenzi, M., Rota, I., Costantino, G., Solbiati, M., Furlan, L., Mancarella, M., Colombo, G., Fanin, A., Passarella, M., Monzani, V., Canetta, C., Rovellini, A., Barbetta, L., Billi, F., Folli, C., Accordino, S., Maira, D., C. M., Hu, Motta, I., Scaramellini, N., Fracanzani, A. L., Lombardi, R., Cespiati, A., Cesari, M., Lucchi, T., Proietti, M., Calcaterra, L., Mandelli, C., Coppola, C., Cerizza, A., Pesenti, A. M., Grasselli, G., Galazzi, A., Monti, I., Galbussera, A. A., Crisafulli, E., Girelli, D., Maroccia, A., Gabbiani, D., Busti, F., Vianello, A., Biondan, M., Sartori, F., Faverio, P., Pesci, A., Zucchetti, S., Bonfanti, P., Rossi, M., Beretta, I., Spolti, A., Elia, D., Cassandro, R., Caminati, A., Cipollone, F., Guagnano, M. T., D'Ardes, D., Rossi, I., Vezzani, F., Spanevello, A., Cherubino, F., Visca, D., Contoli, M., Papi, A., Morandi, L., Battistini, N., Moreo, G. L., Iannuzzi, P., Fumagalli, D., Leone, S., Bandera, A, Nobili, A, Tettamanti, M, Harari, S, Bosari, S, Mannucci, P, Scudeller, L, Fusetti, G, Rusconi, L, Dell'Orto, S, Prati, D, Valenti, L, Giovannelli, S, Manunta, M, Lamorte, G, Ferrari, F, Gori, A, Muscatello, A, Mangioni, D, Alagna, L, Bozzi, G, Lombardi, A, Ungaro, R, Ancona, G, Zuglian, G, Bolis, M, Iannotti, N, Ludovisi, S, Comelli, A, Renisi, G, Biscarini, S, Castelli, V, Palomba, E, Fava, M, Fortina, V, Peri, C, Saltini, P, Viero, G, Itri, T, Ferroni, V, Pastore, V, Massafra, R, Liparoti, A, Muheberimana, T, Giommi, A, Bianco, R, De Azevedo, R, Chitani, G, Peyvandi, F, Gualtierotti, R, Ferrari, B, Rossio, R, Boasi, N, Pagliaro, E, Massimo, C, De Caro, M, Montano, N, Vigone, B, Bellocchi, C, Carandina, A, Fiorelli, E, Melli, V, Tobaldini, E, Blasi, F, Aliberti, S, Spotti, M, Terranova, L, Misuraca, S, D'Adda, A, Della Fiore, S, Di Pasquale, M, Contarini, M, Ori, M, Morlacchi, L, Rossetti, V, Gramegna, A, Pappalettera, M, Cavallini, M, Buscemi, A, Vicenzi, M, Rota, I, Costantino, G, Solbiati, M, Furlan, L, Mancarella, M, Colombo, G, Fanin, A, Passarella, M, Monzani, V, Canetta, C, Rovellini, A, Barbetta, L, Billi, F, Folli, C, Accordino, S, Maira, D, Hu, C, Motta, I, Scaramellini, N, Fracanzani, A, Lombardi, R, Cespiati, A, Cesari, M, Lucchi, T, Proietti, M, Calcaterra, L, Mandelli, C, Coppola, C, Cerizza, A, Pesenti, A, Grasselli, G, Galazzi, A, Monti, I, Galbussera, A, Crisafulli, E, Girelli, D, Maroccia, A, Gabbiani, D, Busti, F, Vianello, A, Biondan, M, Sartori, F, Faverio, P, Pesci, A, Zucchetti, S, Bonfanti, P, Rossi, M, Beretta, I, Spolti, A, Elia, D, Cassandro, R, Caminati, A, Cipollone, F, Guagnano, M, D'Ardes, D, Rossi, I, Vezzani, F, Spanevello, A, Cherubino, F, Visca, D, Contoli, M, Papi, A, Morandi, L, Battistini, N, Moreo, G, Iannuzzi, P, Fumagalli, D, and Leone, S
Subjects: Adult, medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Critical Care, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Ce - Letter to the Editor, MEDLINE, Cohort Studies, Hospital, Internal Medicine, Medicine, Humans, Hospital Mortality, Intensive care medicine, Aged, Aged, 80 and over, business.industry, SARS-CoV-2, COVID-19, Middle Aged, Respiration, Artificial, Hospitals, Hospitalization, Survival Rate, Italy, Emergency Medicine, business, Human
Abstract: During the COVID-19 2020 outbreak, a large body of data has been provided on general management and outcomes of hospitalized COVID-19 patients. Yet, relatively little is known on characteristics and outcome of patients managed in Internal Medicine Units (IMU). To address this gap, the Italian Society of Internal Medicine has conducted a nationwide cohort multicentre study on death outcome in adult COVID-19 patients admitted and managed in IMU. This study assessed 3044 COVID-19 patients at 41 referral hospitals across Italy from February 3rd to May 8th 2020. Demographics, comorbidities, organ dysfunction, treatment, and outcomes including death were assessed. During the study period, 697 patients (22.9%) were transferred to intensive care units, and 351 died in IMU (death rate 14.9%). At admission, factors independently associated with in-hospital mortality were age (OR 2.46, p = 0.000), productive cough (OR 2.04, p = 0.000), pre-existing chronic heart failure (OR 1.58, p = 0.017) and chronic obstructive pulmonary disease (OR 1.17, p = 0.048), the number of comorbidities (OR 1.34, p = 0.000) and polypharmacy (OR 1.20, p = 0.000). Of note, up to 40% of elderly patients did not report fever at admission. Decreasing PaO
Published: 2022

5. Clinical risk scores for the early prediction of severe outocomes in patients hospitalized for COVID-19: comment

Author: Rossio R., Tettamanti M., Nobili A., Harari S., Mannucci P. M., Bandera A., Peyvandi F., Bosari S., Scudeller L., Fusetti G., Rusconi L., Dell'Orto S., Prati D., Valenti L., Giovannelli S., Manunta M., Lamorte G., Ferrari F., Gori A., Muscatello A., Mangioni D., Alagna L., Bozzi G., Lombardi A., Ungaro R., Ancona G., Zuglian G., Bolis M., Iannotti N., Ludovisi S., Comelli A., Renisi G., Biscarini S., Castelli V., Palomba E., Fava M., Fortina V., Peri C. A., Saltini P., Viero G., Itri T., Ferroni V., Pastore V., Massafra R., Liparoti A., Muheberimana T., Giommi A., Bianco R., De Azevedo R. M., Chitani G. E., Gualtierotti R., Ferrari B., Boasi N., Pagliaro E., Massimo C., De Caro M., Giachi A., Montano N., Vigone B., Bellocchi C., Carandina A., Fiorelli E., Melli V., Tobaldini E., Blasi F., Aliberti S., Spotti M., Terranova L., Misuraca S., D'Adda A., Fiore S. D., Di Pasquale M., Mantero M., Contarini M., Ori M., Morlacchi L., Rossetti V., Gramegna A., Pappalettera M., Cavallini M., Buscemi A., Vicenzi M., Rota I., Costantino G., Solbiati M., Furlan L., Mancarella M., Colombo G., Fanin A., Passarella M., Monzani V., Canetta C., Rovellini A., Barbetta L., Billi F., Folli C., Accordino S., Maira D., Hu C. M., Motta I., Scaramellini N., Fracanzani A. L., Lombardi R., Cespiati A., Cesari M., Lucchi T., Proietti M., Calcaterra L., Mandelli C., Coppola C., Cerizza A., Pesenti A. M., Grasselli G., Galazzi A., Monti I., Galbussera A. A., Crisafulli E., Girelli D., Maroccia A., Gabbiani D., Busti F., Vianello A., Biondan M., Sartori F., Faverio P., Pesci A., Zucchetti S., Bonfanti P., Rossi M., Beretta I., Spolti A., Elia D., Cassandro R., Caminati A., Cipollone F., Guagnano M. T., D'Ardes D., Rossi I., Vezzani F., Spanevello A., Cherubino F., Visca D., Contoli M., Papi A., Morandi L., Battistini N., Moreo G. L., Iannuzzi P., Fumagalli D., Leone S., Rossio, R, Tettamanti, M, Nobili, A, Harari, S, Mannucci, P, Bandera, A, Peyvandi, F, Bosari, S, Scudeller, L, Fusetti, G, Rusconi, L, Dell'Orto, S, Prati, D, Valenti, L, Giovannelli, S, Manunta, M, Lamorte, G, Ferrari, F, Gori, A, Muscatello, A, Mangioni, D, Alagna, L, Bozzi, G, Lombardi, A, Ungaro, R, Ancona, G, Zuglian, G, Bolis, M, Iannotti, N, Ludovisi, S, Comelli, A, Renisi, G, Biscarini, S, Castelli, V, Palomba, E, Fava, M, Fortina, V, Peri, C, Saltini, P, Viero, G, Itri, T, Ferroni, V, Pastore, V, Massafra, R, Liparoti, A, Muheberimana, T, Giommi, A, Bianco, R, De Azevedo, R, Chitani, G, Gualtierotti, R, Ferrari, B, Boasi, N, Pagliaro, E, Massimo, C, De Caro, M, Giachi, A, Montano, N, Vigone, B, Bellocchi, C, Carandina, A, Fiorelli, E, Melli, V, Tobaldini, E, Blasi, F, Aliberti, S, Spotti, M, Terranova, L, Misuraca, S, D'Adda, A, Fiore, S, Di Pasquale, M, Mantero, M, Contarini, M, Ori, M, Morlacchi, L, Rossetti, V, Gramegna, A, Pappalettera, M, Cavallini, M, Buscemi, A, Vicenzi, M, Rota, I, Costantino, G, Solbiati, M, Furlan, L, Mancarella, M, Colombo, G, Fanin, A, Passarella, M, Monzani, V, Canetta, C, Rovellini, A, Barbetta, L, Billi, F, Folli, C, Accordino, S, Maira, D, Hu, C, Motta, I, Scaramellini, N, Fracanzani, A, Lombardi, R, Cespiati, A, Cesari, M, Lucchi, T, Proietti, M, Calcaterra, L, Mandelli, C, Coppola, C, Cerizza, A, Pesenti, A, Grasselli, G, Galazzi, A, Monti, I, Galbussera, A, Crisafulli, E, Girelli, D, Maroccia, A, Gabbiani, D, Busti, F, Vianello, A, Biondan, M, Sartori, F, Faverio, P, Pesci, A, Zucchetti, S, Bonfanti, P, Rossi, M, Beretta, I, Spolti, A, Elia, D, Cassandro, R, Caminati, A, Cipollone, F, Guagnano, M, D'Ardes, D, Rossi, I, Vezzani, F, Spanevello, A, Cherubino, F, Visca, D, Contoli, M, Papi, A, Morandi, L, Battistini, N, Moreo, G, Iannuzzi, P, Fumagalli, D, and Leone, S
Subjects: Male, Outcome Assessment, Disease, 030204 cardiovascular system & hematology, Respiratory failure, 0302 clinical medicine, Risk Factors, Epidemiology, Early prediction, Outcome Assessment, Health Care, 030212 general & internal medicine, Framingham Risk Score, Respiration, Area under the curve, Middle Aged, Hospitalization, Survival Rate, Italy, Artificial, Emergency Medicine, Female, Clinical risk factor, 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Ce - Letter to the Editor, MEDLINE, Risk Assessment, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, Internal Medicine, medicine, Intubation, Intratracheal, Humans, In patient, Derivation, COVID-19, Risk prediction model, SARS-CoV 2, Selection (genetic algorithm), Aged, Retrospective Studies, SARS-CoV-2, business.industry, Retrospective cohort study, Respiration, Artificial, Im - Original, Health Care, Intratracheal, ROC Curve, Intubation, business
Abstract: Coronavirus disease of 2019 (COVID-19) is associated with severe acute respiratory failure. Early identification of high-risk COVID-19 patients is crucial. We aimed to derive and validate a simple score for the prediction of severe outcomes. A retrospective cohort study of patients hospitalized for COVID-19 was carried out by the Italian Society of Internal Medicine. Epidemiological, clinical, laboratory, and treatment variables were collected at hospital admission at five hospitals. Three algorithm selection models were used to construct a predictive risk score: backward Selection, Least Absolute Shrinkage and Selection Operator (LASSO), and Random Forest. Severe outcome was defined as the composite of need for non-invasive ventilation, need for orotracheal intubation, or death. A total of 610 patients were included in the analysis, 313 had a severe outcome. The subset for the derivation analysis included 335 patients, the subset for the validation analysis 275 patients. The LASSO selection identified 6 variables (age, history of coronary heart disease, CRP, AST, D-dimer, and neutrophil/lymphocyte ratio) and resulted in the best performing score with an area under the curve of 0.79 in the derivation cohort and 0.80 in the validation cohort. Using a cut-off of 7 out of 13 points, sensitivity was 0.93, specificity 0.34, positive predictive value 0.59, and negative predictive value 0.82. The proposed score can identify patients at low risk for severe outcome who can be safely managed in a low-intensity setting after hospital admission for COVID-19.
Published: 2021

6. Development of a Risk Prediction Model for Carbapenem-resistant Enterobacteriaceae Infection after Liver Transplantation: A Multinational Cohort Study

Author: Giannella, M., Freire, M., Rinaldi, M., Abdala, E., Rubin, A., Mularoni, A., Gruttadauria, S., Grossi, P., Shbaklo, N., Tandoi, F., Ferrarese, A., Burra, P., Fernandes, R., Aranha Camargo, L. F., Asensio, A., Alagna, L., Bandera, A., Simkins, J., Abbo, L., Halpern, M., Santana Girao, E., Valerio, M., Munoz, P., Fernandez Yunquera, A., Statlender, L., Yahav, D., Franceschini, E., Graziano, E., Morelli, M. C., Cescon, M., Viale, P., Lewis, R., Bartoletti, M., Pascale, R., Campoli, C., Coladonato, S., Cristini, F., Tumietto, F., Siniscalchi, A., Laici, C., Ambretti, S., Romagnoli, R., De Rosa, F. G., Muscatello, A., Mangioni, D., Gori, A., Antonelli, B., Dondossola, D., Rossi, G., Invernizzi, F., Peghin, M., Cillo, U., Mussini, C., Benedetto, F. D., Terrabuio, D. R. B., Bittante, C. D., Toniolo, A. D. R., Balbi, E., Garcia, J. H. P., Morras, I., Ramos, A., Cruz, A. F., Salcedo, M., Giannella M., Freire M., Rinaldi M., Abdala E., Rubin A., Mularoni A., Gruttadauria S., Grossi P., Shbaklo N., Tandoi F., Ferrarese A., Burra P., Fernandes R., Aranha Camargo L.F., Asensio A., Alagna L., Bandera A., Simkins J., Abbo L., Halpern M., Santana Girao E., Valerio M., Munoz P., Fernandez Yunquera A., Statlender L., Yahav D., Franceschini E., Graziano E., Morelli M.C., Cescon M., Viale P., Lewis R., Bartoletti M., Pascale R., Campoli C., Coladonato S., Cristini F., Tumietto F., Siniscalchi A., Laici C., Ambretti S., Romagnoli R., De Rosa F.G., Muscatello A., Mangioni D., Gori A., Antonelli B., Dondossola D., Rossi G., Invernizzi F., Peghin M., Cillo U., Mussini C., Benedetto F.D., Terrabuio D.R.B., Bittante C.D., Toniolo A.D.R., Balbi E., Garcia J.H.P., Morras I., Ramos A., Cruz A.F., and Salcedo M.
Subjects: Microbiology (medical), Adult, medicine.medical_specialty, medicine.medical_treatment, Carbapenem-resistant enterobacteriaceae, Liver transplantation, CRE carriage, CRE infection, SOT, liver transplantation, Anti-Bacterial Agents, Carbapenems, Cohort Studies, Humans, Risk Factors, Carbapenem-Resistant Enterobacteriaceae, Enterobacteriaceae Infections, Liver Transplantation, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, Anti-Bacterial Agent, Medicine, 030212 general & internal medicine, Carbapenem, Univariate analysis, business.industry, Risk Factor, Area under the curve, Nomogram, Enterobacteriaceae Infection, Transplantation, Infectious Diseases, 030211 gastroenterology & hepatology, Cohort Studie, business, Human, Cohort study
Abstract: BackgroundPatients colonized with carbapenem-resistant Enterobacteriaceae (CRE) are at higher risk of developing CRE infection after liver transplantation (LT), with associated high morbidity and mortality. Prediction model for CRE infection after LT among carriers could be useful to target preventive strategies.MethodsMultinational multicenter cohort study of consecutive adult patients underwent LT and colonized with CRE before or after LT, from January 2010 to December 2017. Risk factors for CRE infection were analyzed by univariate analysis and by Fine-Gray subdistribution hazard model, with death as competing event. A nomogram to predict 30- and 60-day CRE infection risk was created.ResultsA total of 840 LT recipients found to be colonized with CRE before (n = 203) or after (n = 637) LT were enrolled. CRE infection was diagnosed in 250 (29.7%) patients within 19 (interquartile range [IQR], 9–42) days after LT. Pre- and post-LT colonization, multisite post-LT colonization, prolonged mechanical ventilation, acute renal injury, and surgical reintervention were retained in the prediction model. Median 30- and 60-day predicted risk was 15% (IQR, 11–24) and 21% (IQR, 15–33), respectively. Discrimination and prediction accuracy for CRE infection was acceptable on derivation (area under the curve [AUC], 74.6; Brier index, 16.3) and bootstrapped validation dataset (AUC, 73.9; Brier index, 16.6). Decision-curve analysis suggested net benefit of model-directed intervention over default strategies (treat all, treat none) when CRE infection probability exceeded 10%. The risk prediction model is freely available as mobile application at https://idbologna.shinyapps.io/CREPostOLTPredictionModel/.ConclusionsOur clinical prediction tool could enable better targeting interventions for CRE infection after transplant.
Published: 2021

7. Effect of anakinra on mortality in patients with COVID-19: a systematic review and patient-level meta-analysis

Author: Kyriazopoulou, E. Huet, T. Cavalli, G. Gori, A. Kyprianou, M. Pickkers, P. Eugen-Olsen, J. Clerici, M. Veas, F. Chatellier, G. Kaplanski, G. Netea, M.G. Pontali, E. Gattorno, M. Cauchois, R. Kooistra, E. Kox, M. Bandera, A. Beaussier, H. Mangioni, D. Dagna, L. van der Meer, J.W.M. Giamarellos-Bourboulis, E.J. Hayem, G. Netea, M.G. van der Meer, J.W.M. Giamarellos-Bourboulis, E.J. Volpi, S. Sormani, M.P. Signori, A. Bozzi, G. Minoia, F. Aliberti, S. Grasselli, G. Alagna, L. Lombardi, A. Ungaro, R. Agostoni, C. Blasi, F. Costantino, G. Fracanzani, A.L. Montano, N. Peyvandi, F. Sottocorno, M. Muscatello, A. Filocamo, G. Papadopoulos, A. Mouktaroudi, M. Karakike, E. Saridaki, M. Gkavogianni, T. Katrini, K. Vechlidis, N. Avgoustou, C. Chalvatzis, S. Marantos, T. Damoulari, C. Damoraki, G. Ktena, S. Tsilika, M. Koufargyris, P. Karageorgos, A. Droggiti, D.-I. Koliakou, A. Poulakou, G. Tsiakos, K. Myrodia, D.-M. Gravvani, A. Trontzas, I.P. Syrigos, K. Kalomenidis, I. Kranidioti, E. Panagopoulos, P. Petrakis, V. Metallidis, S. Loli, G. Tsachouridou, O. Dalekos, G.N. Gatselis, N. Stefos, A. Georgiadou, S. Lygoura, V. Milionis, H. Kosmidou, M. Papanikolaou, I.C. Akinosoglou, K. Giannitsioti, E. Chrysos, G. Mavroudis, P. Sidiropoulou, C. Adamis, G. Fragkou, A. Rapti, A. Alexiou, Z. Symbardi, S. Masgala, A. Kostaki, K. Kostis, E. Samarkos, M. Bakakos, P. Tzavara, V. Dimakou, K. Tzatzagou, G. Chini, M. Kotsis, V. Tsoukalas, G. Bliziotis, I. Doumas, M. Argyraki, A. Kainis, I. Fantoni, M. Cingolani, A. Angheben, A. Cardellino, C.S. Castelli, F. Serino, F.S. Nicastri, E. Ippolito, G. Bassetti, M. Selmi, C. International Collaborative Group for Anakinra in COVID-19
Abstract: Background: Anakinra might improve the prognosis of patients with moderate to severe COVID-19 (ie, patients requiring oxygen supplementation but not yet receiving organ support). We aimed to assess the effect of anakinra treatment on mortality in patients admitted to hospital with COVID-19. Methods: For this systematic review and individual patient-level meta-analysis, a systematic literature search was done on Dec 28, 2020, in Medline (PubMed), Cochrane, medRxiv, bioRxiv, and the ClinicalTrials.gov databases for randomised trials, comparative studies, and observational studies of patients admitted to hospital with COVID-19, comparing administration of anakinra with standard of care, or placebo, or both. The search was repeated on Jan 22, 2021. Individual patient-level data were requested from investigators and corresponding authors of eligible studies; if individual patient-level data were not available, published data were extracted from the original reports. The primary endpoint was mortality after 28 days and the secondary endpoint was safety (eg, the risk of secondary infections). This study is registered on PROSPERO (CRD42020221491). Findings: 209 articles were identified, of which 178 full-text articles fulfilled screening criteria and were assessed. Aggregate data on 1185 patients from nine studies were analysed, and individual patient-level data on 895 patients were provided from six of these studies. Eight studies were observational and one was a randomised controlled trial. Most studies used historical controls. In the individual patient-level meta-analysis, after adjusting for age, comorbidities, baseline ratio of the arterial partial oxygen pressure divided by the fraction of inspired oxygen (PaO2/FiO2), C-reactive protein (CRP) concentrations, and lymphopenia, mortality was significantly lower in patients treated with anakinra (38 [11%] of 342) than in those receiving standard of care with or without placebo (137 [25%] of 553; adjusted odds ratio [OR] 0·32 [95% CI 0·20–0·51]). The mortality benefit was similar across subgroups regardless of comorbidities (ie, diabetes), ferritin concentrations, or the baseline PaO2/FiO2. In a subgroup analysis, anakinra was more effective in lowering mortality in patients with CRP concentrations higher than 100 mg/L (OR 0·28 [95% CI 0·17–0·47]). Anakinra showed a significant survival benefit when given without dexamethasone (OR 0·23 [95% CI 0·12–0·43]), but not with dexamethasone co-administration (0·72 [95% CI 0·37–1·41]). Anakinra was not associated with a significantly increased risk of secondary infections when compared with standard of care (OR 1·35 [95% CI 0·59–3·10]). Interpretation: Anakinra could be a safe, anti-inflammatory treatment option to reduce the mortality risk in patients admitted to hospital with moderate to severe COVID-19 pneumonia, especially in the presence of signs of hyperinflammation such as CRP concentrations higher than 100 mg/L. Funding: Sobi. © 2021 Elsevier Ltd
Published: 2021

8. COVID-19 Network: the response of an Italian Reference Institute to research challenges about a new pandemia

Author: Bosari, S., Scudeller, L., Fusetti, G., Rusconi, L., Dell Orto, S., Prati, D., Valenti, L., Lamorte, G., Manunta, M., Baselli, G., Santoro, L., Gori, A., Bandera, A., Muscatello, A., Mangioni, D., Alagna, L., Bozzi, G., Lombardi, A., Ungaro, R., Itri, T., Ferroni, V., Pastore, V., Massafra, R., Rondolini, I., Peyvandi, F., Gualtierotti, R., Ferrari, B., Rossio, R., Corona, E., Rampi, N., Massimo, C., Montano, N., Vigone, B., Bellocchi, C., Fiorelli, E., Melli, V., Tobaldini, E., Blasi, F., Aliberti, S., Spotti, M., Simonetta, E., Terranova, L., Amati, F., Miele, C., Misuraca, S., D'Adda, A., Della Fiore, S., Di Pasquale, M., Contarini, M.M.M., Ori, M., Morlacchi, L., Rossetti, V., Gramegna, A., Pappalettera, M., Cavallini, M., Vigni, A., Vicenzi, M., Rota, I., Costantino, G., Solbiati, M., Furlan, L., Mancarella, M., Colombo, G., Fanin, A., Monzani, V., Rovellini, A., Barbetta, L., Billi, F., Folli, C., Baldini, M., Motta, I., Scaramellini, N., Fracanzani, A.L., Lombardi, R., Iuculano, F., Cesari, M., Proietti, M., Calcaterra, L., Nobili, A., Tettamanti, M., Monti, I., and Pesenti, A.
Published: 2020
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9. COVID-19 Network: the response of an Italian Reference Institute to research challenges about a new pandemia

Author: Bandera, A., primary, Aliberti, S., additional, Gualtierotti, R., additional, Baldini, M., additional, Blasi, F., additional, Cesari, M., additional, Costantino, G., additional, Fracanzani, A.L., additional, Gori, A., additional, Montano, N., additional, Monzani, V., additional, Nobili, A., additional, Peyvandi, F., additional, Pesenti, A., additional, Prati, D., additional, Valenti, L., additional, Fusetti, G., additional, Scudeller, L., additional, Bosari, S., additional, Rusconi, L., additional, Dell Orto, S., additional, Lamorte, G., additional, Manunta, M., additional, Baselli, G., additional, Santoro, L., additional, Bandera, A., additional, Muscatello, A., additional, Mangioni, D., additional, Alagna, L., additional, Bozzi, G., additional, Lombardi, A., additional, Ungaro, R., additional, Itri, T., additional, Ferroni, V., additional, Pastore, V., additional, Massafra, R., additional, Rondolini, I., additional, Ferrari, B., additional, Rossio, R., additional, Corona, E., additional, Rampi, N., additional, Massimo, C., additional, Vigone, B., additional, Bellocchi, C., additional, Fiorelli, E., additional, Melli, V., additional, Tobaldini, E., additional, Spotti, M., additional, Simonetta, E., additional, Terranova, L., additional, Amati, F., additional, Miele, C., additional, Misuraca, S., additional, D'Adda, A., additional, Della Fiore, S., additional, Di Pasquale, M., additional, Contarini, M.M.M., additional, Ori, M., additional, Morlacchi, L., additional, Rossetti, V., additional, Gramegna, A., additional, Pappalettera, M., additional, Cavallini, M., additional, Vigni, A., additional, Vicenzi, M., additional, Rota, I., additional, Solbiati, M., additional, Furlan, L., additional, Mancarella, M., additional, Colombo, G., additional, Fanin, A., additional, Rovellini, A., additional, Barbetta, L., additional, Billi, F., additional, Folli, C., additional, Motta, I., additional, Scaramellini, N., additional, Lombardi, R., additional, Iuculano, F., additional, Proietti, M., additional, Calcaterra, L., additional, Tettamanti, M., additional, and Monti, I., additional
Published: 2020
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10. 10-Year microbiological scenario of uropathogens in a single tertiary centre and the distinctive features of the urology department

Author: Ripa, F., primary, Rocchini, L., additional, Bebi, C., additional, Boeri, L., additional, Longo, F., additional, De Lorenzis, E., additional, Albo, G., additional, Mangioni, D., additional, Bandera, A., additional, and Montanari, E., additional
Published: 2020
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11. Multi-Criteria Decision Analysis to prioritize hospital admission of patients affected by COVID-19 in low-resource settings with hospital-bed shortage

Author: De Nardo, Pasquale, primary, Gentilotti, Elisa, additional, Mazzaferri, Fulvia, additional, Cremonini, Eleonora, additional, Hansen, Paul, additional, Goossens, Herman, additional, Tacconelli, Evelina, additional, Durante Mangoni, E., additional, Florio, L.L., additional, Zampino, R., additional, Mele, F., additional, Gentile, I., additional, Pinchera, B., additional, Coppola, N., additional, Pisaturo, M., additional, Luzzati, R., additional, Petrosillo, N., additional, Nicastri, E., additional, Corpolongo, A., additional, Cataldo, M.A., additional, D’Abramo, A., additional, Maffongelli, G., additional, Scorzolini, L., additional, Palazzolo, C., additional, Boumis, E., additional, Pan, A., additional, D’Arminio Monforte, A., additional, Bai, F., additional, Antinori, S., additional, De Rosa, F.G., additional, Corcione, S., additional, Lupia, T., additional, Pinna, S.M., additional, Scabini, S., additional, Canta, F., additional, Belloro, S., additional, Bisoffi, Z., additional, Angheben, A., additional, Gobbi, F., additional, Turcato, E., additional, Ronzoni, N., additional, Moro, L., additional, Calabria, S., additional, Rodari, P., additional, Bertoli, G., additional, Marasca, G., additional, Puoti, M., additional, Gori, A., additional, Bandera, A., additional, Mangioni, D., additional, Rizzi, M., additional, Castelli, F., additional, Montineri, A., additional, Coco, C.A., additional, Maresca, M., additional, Frasca, M., additional, Aquilini, D., additional, Vincenzi, M., additional, Lambertenghi, L., additional, De Rui, M.E., additional, Razzaboni, E., additional, Cattaneo, P., additional, Visentin, A., additional, Erbogasto, A., additional, Dalla Vecchia, I., additional, Coledan, I., additional, Vecchi, M., additional, Be, G., additional, Motta, L., additional, Zaffagnini, A., additional, Auerbach, N., additional, Del Bravo, P., additional, Azzini, A.M., additional, Righi, E., additional, Carrara, E., additional, Savoldi, A., additional, Sibani, M., additional, Lattuada, E., additional, Carolo, G., additional, Cordioli, M., additional, Soldani, F., additional, Pezzani, M.D., additional, Avallone, S., additional, Bruno, R., additional, Ricciardi, A., additional, Saggese, M.P., additional, and Malerba, G., additional
Published: 2020
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12. Duration of quarantine in hospitalized patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection: a question needing an answer

Author: Lombardi, A., primary, Alagna, L., additional, Bozzi, G., additional, Mangioni, D., additional, Muscatello, A., additional, Peri, A.M., additional, Taramasso, L., additional, Ungaro, R., additional, Bandera, A., additional, and Gori, A., additional
Published: 2020
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13. The role of immune suppression in COVID-19 hospitalization: clinical and epidemiological trends over three years of SARS-CoV-2 epidemic

Author: Marta Canuti, Maria Cristina Monti, Chiara Bobbio, Antonio Muscatello, Toussaint Muheberimana, Sante Leandro Baldi, Francesco Blasi, Ciro Canetta, Giorgio Costantino, Alessandro Nobili, Flora Peyvandi, Mauro Tettamanti, Simone Villa, Stefano Aliberti, Mario C. Raviglione, Andrea Gori, Alessandra Bandera, COVID-19 Network Study Group, Bosari Silvano, Scudeller Luigia, Fusetti Giuliana, Rusconi Laura, Dell’Orto Silvia, Prati Daniele, Valenti Luca, Giovannelli Silvia, Manunta Maria, Lamorte Giuseppe, Ferarri Francesca, Mangioni Davide, Alagna Laura, Bozzi Giorgio, Lombardi Andrea, Ungaro Riccardo, Ancona Giuseppe, Zuglian Gianluca, Bolis Matteo, Iannotti Nathalie, Ludovisi Serena, Comelli Agnese, Renisi Giulia, Biscarini Simona, Castelli Valeria, Palomba Emanuele, Fava Marco, Fortina Valeria, Liparoti Arianna, Pastena Andrea, Alberto Peri Carlo, Saltini Paola, Viero Giulia, Itri Teresa, Ferroni Valentina, Pastore Valeria, Massafra Roberta, Curri Maria Teresa, Rizzo Alice, Scarpa Stefano, Giommi Alessandro, Bianco Rosaria, Chitani Grazia Eliana, Gualtierotti Roberta, Ferrari Barbara, Rossio Raffaella, Boasi Nadia, Pagliaro Erica, Massimo Costanza, Caro Michele De, Giachi Andrea, Montano Nicola, Vigone Barbara, Bellocchi Chiara, Carandina Angelica, Fiorelli Elisa, Melli Valerie, Tobaldini Eleonora, Spotti Maura, Terranova Leonardo, Misuraca Sofia, D’Adda Alice, Fiore Silvia Della, Pasquale Marta Di, Mantero Marco, Contarini Martina, Ori Margherita, Morlacchi Letizia, Rossetti Valeria, Gramegna Andrea, Pappalettera Maria, Cavallini Mirta, Buscemi Agata, Vicenzi Marco, Rota Irena, Solbiati Monica, Furlan Ludovico, Mancarella Marta, Colombo Giulia, Colombo Giorgio, Fanin Alice, Passarella Mariele, Monzani Valter, Rovellini Angelo, Barbetta Laura, Billi Filippo, Folli Christian, Accordino Silvia, Maira Diletta, Hu Cinzia Maria, Motta Irene, Scaramellini Natalia, Fracanzani Anna Ludovica, Lombardi Rosa, Cespiati Annalisa, Cesari Matteo, Lucchi Tiziano, Proietti Marco, Calcaterra Laura, Mandelli Clara, Coppola Carlotta, Cerizza Arturo, Grasselli Giacomo, Galazzi Alessandro, Monti Igor, and Galbusera Alessia Antonella
Subjects: SARS-CoV-2, COVID-19, disease outcome, hospitalization, COVID-19 vaccination, immune suppression, Medicine (General), R5-920
Abstract: Specific immune suppression types have been associated with a greater risk of severe COVID-19 disease and death. We analyzed data from patients >17 years that were hospitalized for COVID-19 at the “Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico” in Milan (Lombardy, Northern Italy). The study included 1727 SARS-CoV-2-positive patients (1,131 males, median age of 65 years) hospitalized between February 2020 and November 2022. Of these, 321 (18.6%, CI: 16.8–20.4%) had at least one condition defining immune suppression. Immune suppressed subjects were more likely to have other co-morbidities (80.4% vs. 69.8%, p
Published: 2023
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14. Characterization of immune failure by monocyte activation phenotypes in HIV-infected patients receiving antiretroviral therapy

Author: BANDERA, ALESSANDRA, INCONTRI, ARIANNA, GORI, ANDREA, Mangioni, D, Perseghin, P, Bandera, A, Mangioni, D, Incontri, A, Perseghin, P, and Gori, A
Subjects: Inflammation, Male, Medicine (all), Immunology and Allergy, Female, HIV Infection, Infectious Disease, Monocyte, Human
Published: 2015

15. SC108 - 10-Year microbiological scenario of uropathogens in a single tertiary centre and the distinctive features of the urology department

Author: Ripa, F., Rocchini, L., Bebi, C., Boeri, L., Longo, F., De Lorenzis, E., Albo, G., Mangioni, D., Bandera, A., and Montanari, E.
Published: 2020
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16. Hospital-Acquired Infections in Critically Ill Patients With COVID-19

Author: Antonio Muscatello, Giacomo Bellani, Paolo Bonfanti, Gabriele Fior, Sara Linguadoca, Antonio Pesenti, Alessandra Bandera, Massimiliano Greco, Michele Bartoletti, Massimo Girardis, Irene Coloretti, Paola Morelli, N Bottino, Mario Carlo Raviglione, Gennaro De Pascale, Marianna Meschiari, Marco Ranieri, Giacomo Grasselli, Roberto Fumagalli, Luigia Scudeller, Giuseppe Foti, Daniela Ferlicca, Andrea Forastieri, Antonio Messina, Emanuela Biagioni, Flavia Stefanini, Pierluigi Viale, Marco Franzetti, Maurizio Cecconi, Tommaso Tonetti, Andrea Gori, Massimo Antonelli, Laura Alagna, Vittorio Scaravilli, Amedeo Guzzardella, SL Cutuli, Simone Redaelli, Davide Mangioni, Gianpaola Monti, Grasselli G., Scaravilli V., Mangioni D., Scudeller L., Alagna L., Bartoletti M., Bellani G., Biagioni E., Bonfanti P., Bottino N., Coloretti I., Cutuli S.L., De Pascale G., Ferlicca D., Fior G., Forastieri A., Franzetti M., Greco M., Guzzardella A., Linguadoca S., Meschiari M., Messina A., Monti G., Morelli P., Muscatello A., Redaelli S., Stefanini F., Tonetti T., Antonelli M., Cecconi M., Foti G., Fumagalli R., Girardis M., Ranieri M., Viale P., Raviglione M., Pesenti A., Gori A., Bandera A., Grasselli, G, Scaravilli, V, Mangioni, D, Scudeller, L, Alagna, L, Bartoletti, M, Bellani, G, Biagioni, E, Bonfanti, P, Bottino, N, Coloretti, I, Cutuli, S, De Pascale, G, Ferlicca, D, Fior, G, Forastieri, A, Franzetti, M, Greco, M, Guzzardella, A, Linguadoca, S, Meschiari, M, Messina, A, Monti, G, Morelli, P, Muscatello, A, Redaelli, S, Stefanini, F, Tonetti, T, Antonelli, M, Cecconi, M, Foti, G, Fumagalli, R, Girardis, M, Ranieri, M, Viale, P, Raviglione, M, Pesenti, A, Gori, A, and Bandera, A
Subjects: Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, COVID-19, SARS-CoV-2, critical care, hospital-acquired infections, medicine.medical_treatment, Critical Illness, Critical Care and Intensive Care Medicine, Aged, Cross Infection, Female, Humans, Middle Aged, Pneumonia, Ventilator-Associated, Retrospective Studies, Sepsis, Interquartile range, Internal medicine, Settore MED/41 - ANESTESIOLOGIA, Hospital-acquired infection, Correspondence, medicine, Mechanical ventilation, hospital-acquired infection, Septic shock, business.industry, Incidence (epidemiology), Mortality rate, Ventilator-associated pneumonia, Pneumonia, medicine.disease, Ventilator-Associated, Cardiology and Cardiovascular Medicine, business
Abstract: Background: Few small studies have described hospital-acquired infections (HAIs) occurring in patients with COVID-19. Research Question: What characteristics in critically ill patients with COVID-19 are associated with HAIs and how are HAIs associated with outcomes in these patients? Study Design and Methods: Multicenter retrospective analysis of prospectively collected data including adult patients with severe COVID-19 admitted to eight Italian hub hospitals from February 20, 2020, through May 20, 2020. Descriptive statistics and univariate and multivariate Weibull regression models were used to assess incidence, microbial cause, resistance patterns, risk factors (ie, demographics, comorbidities, exposure to medication), and impact on outcomes (ie, ICU discharge, length of ICU and hospital stays, and duration of mechanical ventilation) of microbiologically confirmed HAIs. Results: Of the 774 included patients, 359 patients (46%) demonstrated 759 HAIs (44.7 infections/1,000 ICU patient-days; 35% multidrug-resistant [MDR] bacteria). Ventilator-associated pneumonia (VAP; n = 389 [50%]), bloodstream infections (BSIs; n = 183 [34%]), and catheter-related BSIs (n = 74 [10%]) were the most frequent HAIs, with 26.0 (95% CI, 23.6-28.8) VAPs per 1,000 intubation-days, 11.7 (95% CI, 10.1-13.5) BSIs per 1,000 ICU patient-days, and 4.7 (95% CI, 3.8-5.9) catheter-related BSIs per 1,000 ICU patient-days. Gram-negative bacteria (especially Enterobacterales) and Staphylococcus aureus caused 64% and 28% of cases of VAP, respectively. Variables independently associated with infection were age, positive end expiratory pressure, and treatment with broad-spectrum antibiotics at admission. Two hundred thirty-four patients (30%) died in the ICU (15.3 deaths/1,000 ICU patient-days). Patients with HAIs complicated by septic shock showed an almost doubled mortality rate (52% vs 29%), whereas noncomplicated infections did not affect mortality. HAIs prolonged mechanical ventilation (median, 24 days [interquartile range (IQR), 14-39 days] vs 9 days [IQR, 5-13 days]; P < .001), ICU stay (24 days [IQR, 16-41 days] vs 9 days [IQR, 6-14 days]; P = .003), and hospital stay (42 days [IQR, 25-59 days] vs 23 days [IQR, 13-34 days]; P < .001). Interpretation: Critically ill patients with COVID-19 are at high risk for HAIs, especially VAPs and BSIs resulting from MDR organisms. HAIs prolong mechanical ventilation and hospitalization, and HAIs complicated by septic shock almost double mortality. Trial Registry: ClinicalTrials.gov; No.: NCT04388670; URL: www.clinicaltrials.gov
Published: 2020

17. Plasma Proteomic Variables Related to COVID-19 Severity: An Untargeted nLC-MS/MS Investigation

Author: Lisa Pagani, Clizia Chinello, Giulia Risca, Giulia Capitoli, Lucrezia Criscuolo, Andrea Lombardi, Riccardo Ungaro, Davide Mangioni, Isabella Piga, Antonio Muscatello, Francesco Blasi, Andrea Favalli, Martina Martinovic, Andrea Gori, Alessandra Bandera, Renata Grifantini, Fulvio Magni, Pagani, L, Chinello, C, Risca, G, Capitoli, G, Criscuolo, L, Lombardi, A, Ungaro, R, Mangioni, D, Piga, I, Muscatello, A, Blasi, F, Favalli, A, Martinovic, M, Gori, A, Bandera, A, Grifantini, R, and Magni, F
Subjects: SARS-CoV-2, Organic Chemistry, severe, COVID-19, General Medicine, Catalysis, Computer Science Applications, Inorganic Chemistry, proteomics, blood, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, plasma, proteomic, mass spectrometry
Abstract: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection leads to a wide range of clinical manifestations and determines the need for personalized and precision medicine. To better understand the biological determinants of this heterogeneity, we explored the plasma proteome of 43 COVID-19 patients with different outcomes by an untargeted liquid chromatography-mass spectrometry approach. The comparison between asymptomatic or pauci-symptomatic subjects (MILDs), and hospitalised patients in need of oxygen support therapy (SEVEREs) highlighted 29 proteins emerged as differentially expressed: 12 overexpressed in MILDs and 17 in SEVEREs. Moreover, a supervised analysis based on a decision-tree recognised three proteins (Fetuin-A, Ig lambda-2chain-C-region, Vitronectin) that are able to robustly discriminate between the two classes independently from the infection stage. In silico functional annotation of the 29 deregulated proteins pinpointed several functions possibly related to the severity; no pathway was associated exclusively to MILDs, while several only to SEVEREs, and some associated to both MILDs and SEVEREs; SARS-CoV-2 signalling pathway was significantly enriched by proteins up-expressed in SEVEREs (SAA1/2, CRP, HP, LRG1) and in MILDs (GSN, HRG). In conclusion, our analysis could provide key information for ‘proteomically’ defining possible upstream mechanisms and mediators triggering or limiting the domino effect of the immune-related response and characterizing severe exacerbations.
Published: 2023

18. Changes in upper airways microbiota in ventilator-associated pneumonia

Author: Laura Alagna, Leonardo Mancabelli, Federico Magni, Liliane Chatenoud, Gabriele Bassi, Silvia Del Bianco, Roberto Fumagalli, Francesca Turroni, Davide Mangioni, Guglielmo M. Migliorino, Christian Milani, Antonio Muscatello, Giovanni Nattino, Edoardo Picetti, Riccardo Pinciroli, Sandra Rossi, Tommaso Tonetti, Alessia Vargiolu, Alessandra Bandera, Marco Ventura, Giuseppe Citerio, Andrea Gori, Alagna, L, Mancabelli, L, Magni, F, Chatenoud, L, Bassi, G, Del Bianco, S, Fumagalli, R, Turroni, F, Mangioni, D, Migliorino, G, Milani, C, Muscatello, A, Nattino, G, Picetti, E, Pinciroli, R, Rossi, S, Tonetti, T, Vargiolu, A, Bandera, A, Ventura, M, Citerio, G, Gori, A, Alagna, Laura, Mancabelli, Leonardo, Magni, Federico, Chatenoud, Liliane, Bassi, Gabriele, Del Bianco, Silvia, Fumagalli, Roberto, Turroni, Francesca, Mangioni, Davide, Migliorino, Guglielmo M, Milani, Christian, Muscatello, Antonio, Nattino, Giovanni, Picetti, Edoardo, Pinciroli, Riccardo, Rossi, Sandra, Tonetti, Tommaso, Vargiolu, Alessia, Bandera, Alessandra, Ventura, Marco, Citerio, Giuseppe, and Gori, Andrea
Subjects: Mechanical ventilation, VAP, Ventilator-associated pneumonia, 16S-rRNA microbial profiling, Critical Care and Intensive Care Medicine, Cohort study, Upper airways microbiota
Abstract: Background The role of upper airways microbiota and its association with ventilator-associated pneumonia (VAP) development in mechanically ventilated (MV) patients is unclear. Taking advantage of data collected in a prospective study aimed to assess the composition and over-time variation of upper airway microbiota in patients MV for non-pulmonary reasons, we describe upper airway microbiota characteristics among VAP and NO-VAP patients. Methods Exploratory analysis of data collected in a prospective observational study on patients intubated for non-pulmonary conditions. Microbiota analysis (trough 16S-rRNA gene profiling) was performed on endotracheal aspirates (at intubation, T0, and after 72 h, T3) of patients with VAP (cases cohort) and a subgroup of NO-VAP patients (control cohort, matched according to total intubation time). Results Samples from 13 VAP patients and 22 NO-VAP matched controls were analyzed. At intubation (T0), patients with VAP revealed a significantly lower microbial complexity of the microbiota of the upper airways compared to NO-VAP controls (alpha diversity index of 84 ± 37 and 160 ± 102, in VAP and NO_VAP group, respectively, p-value Prevotella 7, Fusobacterium, Neisseria, Escherichia–Shigella and Haemophilus) was found in VAP patients. In contrast, eight genera belonging to the Bacteroidetes, Firmicutes and Fusobacteria phyla was predominant in this group. However, it is unclear whether VAP caused dysbiosis or dysbiosis caused VAP. Conclusions In a small sample size of intubated patients, microbial diversity at intubation was less in patients with VAP compared to patients without VAP.
Published: 2023

19. Multiorgan Donor Bronchoalveolar Lavage Positivity: Incidence, Risk Factors, and Lung Transplant Recipients' Outcome.

Author: Fumagalli, J., Rosso, L., Cattaneo, M., Romeo, G., Scaravilli, V., Righi, I., Damarco, F., Mangioni, D., Gori, F., Bandera, A., Rossetti, V., Morlacchi, L., Nosotti, M., Zanella, A., and Grasselli, G.
Subjects: *ARTIFICIAL respiration, *LUNG transplantation, *LENGTH of stay in hospitals, *BRONCHOALVEOLAR lavage, *OPTIMISM, *INTENSIVE care units, *PULMONARY alveolar proteinosis
Abstract: To evaluate the incidence and risk factors for bronchoalveolar lavage (BAL) positivity in lung donors. To measure the rate of donor derived infections (DDI) and the effect of BAL positivity on lung transplant (LuTX) recipients' outcome. Retrospective single center analysis of consecutive LuTX from January 2018 to December 2021. BAL samples were obtained from donors' lungs immediately ahead harvesting and from recipients' lungs at three times after LuTX: day 1-3, 7, and 14. BAL positivity was defined as bacterial growth ≥104 colony forming units. A DDI was defined as growth of the same bacterial species between the donor and the recipient BAL. Recipients' cohort was divided between colonized and not-colonized subjects based on the presence of pre-transplant colonizing disease. Recipients' duration of mechanical ventilation, intensive care unit and hospital length of stay were assessed. 100 LuTX procedures were analyzed out of 104 LuTX performed along the study period. 42 (42%) of donor BAL were positive for at least one bacterial species: Staphylococcus Aureus and Enterobacterales were the predominant causative pathogens. Donors' age, sex, cause of death, duration of mechanical ventilation, and PaO 2 /FiO 2 were not correlated to occurrence of the BAL positive result. Figure 1 illustrates the recipients' BAL results course along the first two weeks after LuTX. Three cases of DDI were detected accounting for 3.4% of all LuTX. No effect was detected in recipients' outcome neither among the colonized and not-colonized cohort. In the present cohort the incidence of positive BAL coltures among lung donors is about 40% and donor characteristics available at the time of harvesting are unable to predict donor BAL positivity. Donor BAL positivity does not affect recipients' outcomes. [ABSTRACT FROM AUTHOR]
Published: 2023
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20. Effect of anakinra on mortality in patients with COVID-19: a systematic review and patient-level meta-analysis

Author: Evdoxia Kyriazopoulou, Thomas Huet, Giulio Cavalli, Andrea Gori, Miltiades Kyprianou, Peter Pickkers, Jesper Eugen-Olsen, Mario Clerici, Francisco Veas, Gilles Chatellier, Gilles Kaplanski, Mihai G Netea, Emanuele Pontali, Marco Gattorno, Raphael Cauchois, Emma Kooistra, Matthijs Kox, Alessandra Bandera, Hélène Beaussier, Davide Mangioni, Lorenzo Dagna, Jos W M van der Meer, Evangelos J Giamarellos-Bourboulis, Gilles Hayem, Mihai G. Netea, Jos W.M. van der Meer, Evangelos J. Giamarellos-Bourboulis, Stefano Volpi, Maria Pia Sormani, Alessio Signori, Giorgio Bozzi, Francesca Minoia, Stefano Aliberti, Giacomo Grasselli, Laura Alagna, Andrea Lombardi, Riccardo Ungaro, Carlo Agostoni, Francesco Blasi, Giorgio Costantino, Anna Ludovica Fracanzani, Nicola Montano, Flora Peyvandi, Marcello Sottocorno, Antonio Muscatello, Giovanni Filocamo, Antonios Papadopoulos, Maria Mouktaroudi, Eleni Karakike, Maria Saridaki, Theologia Gkavogianni, Konstantina Katrini, Nikolaos Vechlidis, Christina Avgoustou, Stamatios Chalvatzis, Theodoros Marantos, Christina Damoulari, Georgia Damoraki, Sofia Ktena, Maria Tsilika, Panagiotis Koufargyris, Athanasios Karageorgos, Dionysia-Irene Droggiti, Aikaterini Koliakou, Garyfallia Poulakou, Konstantinos Tsiakos, Dimitra-Melia Myrodia, Areti Gravvani, Ioannis P. Trontzas, Konstantinos Syrigos, Ioannis Kalomenidis, Eleftheria Kranidioti, Periklis Panagopoulos, Vasileios Petrakis, Simeon Metallidis, Georgia Loli, Olga Tsachouridou, George N. Dalekos, Nikolaos Gatselis, Aggelos Stefos, Sarah Georgiadou, Vassiliki Lygoura, Haralampos Milionis, Maria Kosmidou, Ilias C. Papanikolaou, Karolina Akinosoglou, Efthymia Giannitsioti, Georgios Chrysos, Panagiotis Mavroudis, Chrysanthi Sidiropoulou, Georgios Adamis, Archontoula Fragkou, Aggeliki Rapti, Zoi Alexiou, Styliani Symbardi, Aikaterini Masgala, Konstantina Kostaki, Evangelos Kostis, Michael Samarkos, Petros Bakakos, Vassiliki Tzavara, Katerina Dimakou, Glykeria Tzatzagou, Maria Chini, Vasileios Kotsis, George Tsoukalas, Ioannis Bliziotis, Michael Doumas, Aikaterini Argyraki, Ilias Kainis, Massimo Fantoni, Antonella Cingolani, Andrea Angheben, Chiara Simona Cardellino, Francesco Castelli, Francesco Saverio Serino, Emanuele Nicastri, Giuseppe Ippolito, Matteo Bassetti, Carlo Selmi, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Kyriazopoulou, E., Huet, T., Cavalli, Giulio., Gori, A., Kyprianou, M., Pickkers, P., Eugen-Olsen, J., Clerici, M., Veas, F., Chatellier, G., Kaplanski, G., Netea, M. G., Pontali, E., Gattorno, M., Cauchois, R., Kooistra, E., Kox, M., Bandera, A., Beaussier, H., Mangioni, D., Dagna, L., van der Meer, J. W. M., Giamarellos-Bourboulis, E. J., Hayem, G., Volpi, S., Sormani, M. P., Signori, A., Bozzi, G., Minoia, F., Aliberti, S., Grasselli, G., Alagna, L., Lombardi, A., Ungaro, R., Agostoni, C., Blasi, F., Costantino, G., Fracanzani, A. L., Montano, N., Peyvandi, F., Sottocorno, M., Muscatello, A., Filocamo, G., Papadopoulos, A., Mouktaroudi, M., Karakike, E., Saridaki, M., Gkavogianni, T., Katrini, K., Vechlidis, N., Avgoustou, C., Chalvatzis, S., Marantos, T., Damoulari, C., Damoraki, G., Ktena, S., Tsilika, M., Koufargyris, P., Karageorgos, A., Droggiti, D. -I., Koliakou, A., Poulakou, G., Tsiakos, K., Myrodia, D. -M., Gravvani, A., Trontzas, I. P., Syrigos, K., Kalomenidis, I., Kranidioti, E., Panagopoulos, P., Petrakis, V., Metallidis, S., Loli, G., Tsachouridou, O., Dalekos, G. N., Gatselis, N., Stefos, A., Georgiadou, S., Lygoura, V., Milionis, H., Kosmidou, M., Papanikolaou, I. C., Akinosoglou, K., Giannitsioti, E., Chrysos, G., Mavroudis, P., Sidiropoulou, C., Adamis, G., Fragkou, A., Rapti, A., Alexiou, Z., Symbardi, S., Masgala, A., Kostaki, K., Kostis, E., Samarkos, M., Bakakos, P., Tzavara, V., Dimakou, K., Tzatzagou, G., Chini, M., Kotsis, V., Tsoukalas, G., Bliziotis, I., Doumas, M., Argyraki, A., Kainis, I., Fantoni, M., Cingolani, A., Angheben, A., Cardellino, C. S., Castelli, F., Serino, F. S., Nicastri, E., Ippolito, G., Bassetti, M., and Selmi, C.
Subjects: medicine.medical_specialty, Anakinra, business.industry, Secondary infection, [SDV]Life Sciences [q-bio], Immunology, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Odds ratio, Articles, Placebo, law.invention, Rheumatology, Randomized controlled trial, law, Meta-analysis, Fraction of inspired oxygen, Internal medicine, Clinical endpoint, Immunology and Allergy, Medicine, business, ComputingMilieux_MISCELLANEOUS, medicine.drug
Abstract: Contains fulltext : 237989.pdf (Publisher’s version ) (Closed access) BACKGROUND: Anakinra might improve the prognosis of patients with moderate to severe COVID-19 (ie, patients requiring oxygen supplementation but not yet receiving organ support). We aimed to assess the effect of anakinra treatment on mortality in patients admitted to hospital with COVID-19. METHODS: For this systematic review and individual patient-level meta-analysis, a systematic literature search was done on Dec 28, 2020, in Medline (PubMed), Cochrane, medRxiv, bioRxiv, and the ClinicalTrials.gov databases for randomised trials, comparative studies, and observational studies of patients admitted to hospital with COVID-19, comparing administration of anakinra with standard of care, or placebo, or both. The search was repeated on Jan 22, 2021. Individual patient-level data were requested from investigators and corresponding authors of eligible studies; if individual patient-level data were not available, published data were extracted from the original reports. The primary endpoint was mortality after 28 days and the secondary endpoint was safety (eg, the risk of secondary infections). This study is registered on PROSPERO (CRD42020221491). FINDINGS: 209 articles were identified, of which 178 full-text articles fulfilled screening criteria and were assessed. Aggregate data on 1185 patients from nine studies were analysed, and individual patient-level data on 895 patients were provided from six of these studies. Eight studies were observational and one was a randomised controlled trial. Most studies used historical controls. In the individual patient-level meta-analysis, after adjusting for age, comorbidities, baseline ratio of the arterial partial oxygen pressure divided by the fraction of inspired oxygen (PaO(2)/FiO(2)), C-reactive protein (CRP) concentrations, and lymphopenia, mortality was significantly lower in patients treated with anakinra (38 [11%] of 342) than in those receiving standard of care with or without placebo (137 [25%] of 553; adjusted odds ratio [OR] 0·32 [95% CI 0·20-0·51]). The mortality benefit was similar across subgroups regardless of comorbidities (ie, diabetes), ferritin concentrations, or the baseline PaO(2)/FiO(2). In a subgroup analysis, anakinra was more effective in lowering mortality in patients with CRP concentrations higher than 100 mg/L (OR 0·28 [95% CI 0·17-0·47]). Anakinra showed a significant survival benefit when given without dexamethasone (OR 0·23 [95% CI 0·12-0·43]), but not with dexamethasone co-administration (0·72 [95% CI 0·37-1·41]). Anakinra was not associated with a significantly increased risk of secondary infections when compared with standard of care (OR 1·35 [95% CI 0·59-3·10]). INTERPRETATION: Anakinra could be a safe, anti-inflammatory treatment option to reduce the mortality risk in patients admitted to hospital with moderate to severe COVID-19 pneumonia, especially in the presence of signs of hyperinflammation such as CRP concentrations higher than 100 mg/L. FUNDING: Sobi.
Published: 2021

21. Integrated longitudinal immunophenotypic, transcriptional and repertoire analyses delineate immune responses in COVID-19 patients

Author: Samuele, Notarbartolo, Valeria, Ranzani, Alessandra, Bandera, Paola, Gruarin, Valeria, Bevilacqua, Anna Rita, Putignano, Andrea, Gobbini, Eugenia, Galeota, Cristina, Manara, Mauro, Bombaci, Elisa, Pesce, Elena, Zagato, Andrea, Favalli, Maria Lucia, Sarnicola, Serena, Curti, Mariacristina, Crosti, Martina, Martinovic, Tanya, Fabbris, Federico, Marini, Lorena, Donnici, Mariangela, Lorenzo, Marilena, Mancino, Riccardo, Ungaro, Andrea, Lombardi, Davide, Mangioni, Antonio, Muscatello, Stefano, Aliberti, Francesco, Blasi, Tullia, De Feo, Daniele, Prati, Lara, Manganaro, Francesca, Granucci, Antonio, Lanzavecchia, Raffaele, De Francesco, Andrea, Gori, Renata, Grifantini, Sergio, Abrignani, Notarbartolo, S, Ranzani, V, Bandera, A, Gruarin, P, Bevilacqua, V, Putignano, A, Gobbini, A, Galeota, E, Manara, C, Bombaci, M, Pesce, E, Zagato, E, Favalli, A, Sarnicola, M, Curti, S, Crosti, M, Martinovic, M, Fabbris, T, Marini, F, Donnici, L, Lorenzo, M, Mancino, M, Ungaro, R, Lombardi, A, Mangioni, D, Muscatello, A, Aliberti, S, Blasi, F, De Feo, T, Prati, D, Manganaro, L, Granucci, F, Lanzavecchia, A, De Francesco, R, Gori, A, Grifantini, R, and Abrignani, S
Subjects: Adult, Male, Cell Plasticity, T-Lymphocyte Subset, Antibodies, Viral, Immunophenotyping, Clonal Evolution, T-Lymphocyte Subsets, Humans, Lymphocyte Count, Aged, B-Lymphocytes, SARS-CoV-2, Gene Expression Profiling, B-Lymphocyte, COVID-19, Biomarker, Middle Aged, Immunoglobulin Isotypes, Host-Pathogen Interaction, Immunoglobulin Isotype, Host-Pathogen Interactions, Leukocytes, Mononuclear, Female, Transcriptome, Immunologic Memory, Biomarkers, Human
Abstract: To understand how a protective immune response against SARS-CoV-2 develops over time, we integrated phenotypic, transcriptional and repertoire analyses on PBMCs from mild and severe COVID-19 patients during and after infection, and compared them to healthy donors (HD). A type I IFN-response signature marked all the immune populations from severe patients during the infection. Humoral immunity was dominated by IgG production primarily against the RBD and N proteins, with neutralizing antibody titers increasing post infection and with disease severity. Memory B cells, including an atypical FCRL5+ T-BET+ memory subset, increased during the infection, especially in patients with mild disease. A significant reduction of effector memory, CD8+T cells frequency characterized patients with severe disease. Despite such impairment, we observed robust clonal expansion of CD8+T lymphocytes, while CD4+T cells were less expanded and skewed toward TCMand TH2-like phenotypes. MAIT cells were also expanded, but only in patients with mild disease. Terminally differentiated CD8+GZMB+effector cells were clonally expanded both during the infection and post-infection, while CD8+GZMK+lymphocytes were more expanded post-infection and represented bona fide memory precursor effector cells. TCR repertoire analysis revealed that only highly proliferating T cell clonotypes, which included SARS-CoV-2-specific cells, were maintained post-infection and shared between the CD8+GZMB+and GZMK+subsets. Overall, this study describes the development of immunity against SARS-CoV-2 and identifies an effector CD8+T cell population with memory precursor-like features.
Published: 2021

22. Inflammatory Cytokines Drive CD4+ T-Cell Cycling and Impaired Responsiveness to Interleukin 7: Implications for Immune Failure in HIV Disease

Author: Benigno Rodriguez, Jeffrey M. Hardacre, Carey L. Shive, Scott F. Sieg, Benjamin Kyi, John B. Ammori, Davide Mangioni, Andrea Gori, Joseph C. Mudd, Nicholas T. Funderburg, Timothy W. Schacker, Ari D. Brooks, Jeffrey M. Jacobson, Jacob D. Estes, Michael M. Lederman, Doug A. Bazdar, Shive, C, Mudd, J, Funderburg, N, Sieg, S, Kyi, B, Bazdar, D, Mangioni, D, Gori, A, Jacobson, J, Brooks, A, Hardacre, J, Ammori, J, Estes, J, Schacker, T, Rodriguez, B, and Lederman, M
Subjects: CD4-Positive T-Lymphocytes, Interleukin 1 beta, medicine.medical_treatment, Interleukin-1beta, Interleukin 6, Infectious Disease, HIV Infections, Inflammation, Interleukin 7, Biology, Proinflammatory cytokine, Interleukin-7 Receptor alpha Subunit, Major Articles and Brief Reports, Immune system, Antiretroviral Therapy, Highly Active, medicine, Humans, Immunology and Allergy, HIV Infection, Interleukin-7 receptor, Cells, Cultured, Receptors, Interleukin-7, Interleukin-6, Immune failure, Interleukin-7, Cell Cycle, HIV, Interleukin, Infectious Diseases, Cytokine, CD4-Positive T-Lymphocyte, Immunology, HIV-1, Leukocytes, Mononuclear, biology.protein, medicine.symptom, CD8, Human
Abstract: In successfully treated human immunodeficiency virus (HIV) infection, chronic inflammation often persists and has been identified as a major predictor of morbidity and mortality [1, 2]. Moreover, in treated patients with controlled viremia, immune activation and elevated plasma markers of inflammation have been associated with poor CD4+ T-cell restoration [3, 4]; yet the mechanistic link between persistent immune activation, inflammation, and CD4+ T-cell restoration failure is unknown. Earlier studies of patients with immune restoration failure found a link between higher indices of inflammation with morbidities and mortalities despite antiretroviral therapy (ART)–induced viral suppression [1, 5, 6]. It is not clear, however, whether the relationship between inflammation and immune failure is causal, and if it is, the mechanisms whereby inflammation might promote persistent CD4+ T-cell restoration failure (or vice versa) are not defined. An increase in T-cell turnover is characteristic of untreated HIV infection [5–7], and recent data demonstrate elevated frequencies of cycling CD4+ (but not CD8+) T cells in treated HIV-infected patients with immune restoration failure [3, 8]. Loss of CD127, the interleukin 7 receptor α chain (IL-7Rα), and an imputed failure of homeostatic CD4+ T-cell expansion in response to IL-7 have also been identified in treated HIV infection [9, 10] and may contribute to CD4+ T-cell restoration failure [11]. This work asked whether inflammatory cytokines might contribute to CD4+ T-cell restoration failure in treated HIV infection. By treating peripheral blood mononuclear cells (PBMCs) from healthy subjects with the inflammatory cytokines interleukin 6 (IL-6) or interleukin 1β (IL-1β), we could recapitulate much of the immunophenotype seen in patients with immune restoration failure—decreased expression of CD127 [11, 12] and increased T-cell cycling, especially of memory CD4+ T cells [3, 6, 8, 13]. Importantly, IL-1β is expressed throughout all lymph node (LN) compartments in HIV-infected viremic patients and, while reduced with ART, still remains elevated, compared with levels in uninfected controls, providing in vivo support for our in vitro findings.
Published: 2014

23. Combination versus sequential monotherapy in chronic HBV infection: a mathematical approach

Author: Davide Mangioni, Fabio Zucca, Sergio Foresti, Daniela Bertacchi, Andrea Gori, Bertacchi, D, Zucca, F, Foresti, S, Mangioni, D, and Gori, A
Subjects: Hepatitis B virus, Combination therapy, Stochastic modelling, viral dynamics stochastic modelling, Drug resistance, medicine.disease_cause, Bioinformatics, Quantitative Biology - Quantitative Methods, General Biochemistry, Genetics and Molecular Biology, Virus, Therapeutic approach, Hepatitis B, Chronic, 60J28, Drug Resistance, Viral, Classical Analysis and ODEs (math.CA), FOS: Mathematics, medicine, ordinary differential equations model, Humans, Quantitative Methods (q-bio.QM), General Environmental Science, Pharmacology, Stochastic Processes, Models, Statistical, drug resistance, General Immunology and Microbiology, business.industry, Applied Mathematics, General Neuroscience, Probability (math.PR), General Medicine, deterministic approximation, mutation, Chronic infection, Mathematics - Classical Analysis and ODEs, FOS: Biological sciences, Modeling and Simulation, Drug Therapy, Combination, business, Viral load, Mathematics - Probability
Abstract: Sequential monotherapy is the most widely used therapeutic approach in the treatment of HBV chronic infection. Unfortunately, under therapy, in some patients the hepatitis virus mutates and gives rise to variants which are drug resistant. We conjecture that combination therapy is able to delay drug resistance for a longer time than sequential monotherapy. To study the action of these two therapeutic approaches in the event of unknown mutations and to explain the emergence of drug resistance, we propose a stochastic model for the infection within a patient which is treated with two drugs, either sequentially or contemporaneously, and develops a two-step mutation which is resistant to both drugs. We study the deterministic approximation of our stochastic model and give a biological interpretation of its asymptotic behaviour. We compare the time when this new strain first reaches detectability in the serum viral load. Our results show that the best choice is to start an early combination therapy, which allows to stay drug-resistance free for a longer time., Comment: 21 pages, 2 figures, 3 tables
Published: 2015

24. A case of classic neuromyelitis optica (Devic's syndrome) triggered by pegylated-interferon α

Author: Alessandra Bandera, Davide Mangioni, Andrea Gori, Carlo Ferrarese, Alessandro Soria, Laura Brighina, Mangioni, D, Soria, A, Brighina, L, Bandera, A, Ferrarese, C, and Gori, A
Subjects: Adult, Male, Pediatrics, medicine.medical_specialty, Standard of care, Alpha interferon, Pegylated interferon α, Case Report, Interferon alpha-2, Polyethylene Glycol, Polyethylene Glycols, Interferon, medicine, Humans, Pharmacology (medical), Adverse effect, Pharmacology, Neuromyelitis optica, S syndrome, Pegylated-interferonα, business.industry, Medicine (all), Neuromyelitis Optica, Interferon-alpha, Hepatitis C, Hepatitis C, Chronic, Recombinant Protein, medicine.disease, Recombinant Proteins, Adverse events, Immunology, HCV, business, medicine.drug, Human
Abstract: Background: Despite recent development of direct acting antivirals for treatment of hepatitis C, the current standard of care may still include pegylated-interferon, which is associated with frequent and, at times, serious adverse events. Case presentation: Here we report for the first time on a severe case of classic neuromyelitis optica (i.e., optic-spinal form) in a 32 year-old Egyptian man with chronic hepatitis C treated with pegylated-interferon α2a for 4 months. Conclusions: Treating physicians must be alerted on rare but important unexpected complications of interferon, in order to consider carefully its use especially when they deal with patients not in dire need of urgent treatment.
Published: 2014

25. A Case of Cerebrospinal Fluid Viral Escape on a Dual Antiretroviral Regimen: Worth the Risk?

Author: Marianna Rossi, Carlo De Grandi, Luca Bisi, Antonio Muscatello, Alessandra Bandera, Davide Mangioni, Andrea Gori, Francesca Sabbatini, Alessandro Soria, Nicola Squillace, Mangioni, D, Muscatello, A, Sabbatini, F, Soria, A, Rossi, M, Bisi, L, Squillace, N, De Grandi, C, Gori, A, and Bandera, A
Subjects: Microbiology (medical), Anti-Retroviral Agents, business.industry, Brain, Infectious Disease, Middle Aged, Viral Load, DUAL (cognitive architecture), Magnetic Resonance Imaging, Virology, Regimen, Infectious Diseases, Cerebrospinal fluid, Immunology, RNA, Viral, Medicine, Anti-Retroviral Agent, Female, HIV Infection, business, Viral load, Human
Published: 2014

26. Focal bone lesions in hiv-positive patient treated with tenofovir

Author: Nicola Squillace, Cristina Messa, Luca Guerra, Alessandra Bandera, Davide Mangioni, Antonio Muscatello, Cinzia Crivellaro, Andrea Gori, Mangioni, D, Bandera, A, Muscatello, A, Squillace, N, Crivellaro, C, Guerra, L, Messa, M, and Gori, A
Subjects: Drug, Male, medicine.medical_specialty, Pathology, medicine.drug_class, Anti-HIV Agents, media_common.quotation_subject, Organophosphonates, Renal function, HIV Infections, Case Report, Gastroenterology, Bone remodeling, Medical microbiology, Internal medicine, medicine, Humans, Adverse effect, Tenofovir, media_common, business.industry, Adenine, HIV, virus diseases, Middle Aged, Bone lesions, Regimen, Infectious Diseases, Bone lesion, Antiviral drug, Bone Diseases, business
Abstract: Background Tenofovir is a widely used antiviral drug for the treatment of HIV and HBV infection. Although its side effects on renal function and bone metabolism are well known, there are no reports on focal bone lesions caused by this drug. Our case suggests this new, unusual but important scenario. Case presentation We report on a 46-year-old HIV-positive man treated with an antiretroviral regimen containing tenofovir who suddenly developed localized inflammatory bone lesions. The examinations performed ruled out all the disorders commonly associated with this clinical pattern, and the patient’s conditions improved only after the suspension of tenofovir. Conclusions The case study suggests a rare but severe adverse event, which should be taken into account when physicians treat HIV-positive patients with focal inflammatory bone lesions
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27. Genomic characterization of Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) strains circulating in three university hospitals in Northern Italy over three years.

Author: Fox V, Mangioni D, Renica S, Comelli A, Teri A, Zatelli M, Orena BS, Scuderi C, Cavallero A, Rossi M, Casana M, Mela L, Bielli A, Scutari R, Morelli P, Cariani L, Casari E, Vismara CS, Matinato C, Callegaro A, Bottazzi B, Cassani B, Perno CF, Gori A, Muscatello A, Bandera A, and Alteri C
Subjects: Humans, beta-Lactamases genetics, Cross Infection microbiology, Cross Infection epidemiology, Drug Resistance, Multiple, Bacterial genetics, Genome, Bacterial, Genomics, Hospitals, University, Italy epidemiology, Microbial Sensitivity Tests, Whole Genome Sequencing, Anti-Bacterial Agents pharmacology, Bacterial Proteins genetics, Klebsiella Infections microbiology, Klebsiella Infections epidemiology, Klebsiella pneumoniae genetics, Klebsiella pneumoniae drug effects, Klebsiella pneumoniae isolation & purification, Klebsiella pneumoniae classification, Klebsiella pneumoniae enzymology
Abstract: Objectives: Genomic surveillance of Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) is crucial for virulence, drug-resistance monitoring, and outbreak containment., Methods: Genomic analysis on 87 KPC-Kp strains isolated from 3 Northern Italy hospitals in 2019-2021 was performed by whole genome sequencing (WGS), to characterize resistome, virulome, and mobilome, and to assess potential associations with phenotype resistance and clinical presentation. Maximum Likelihood and Minimum Spanning Trees were used to determine strain correlations and identify potential transmission clusters., Results: Overall, 15 different STs were found; the predominant ones included ST307 (35, 40.2%), ST512/1519 (15, 17.2%), ST20 (12, 13.8%), and ST101 (7, 8.1%). 33 (37.9%) KPC-Kp strains were noticed to be in five transmission clusters (median number of isolates in each cluster: 5 [3-10]), four of them characterized by intra-hospital transmission. All 87 strains harbored Tn4401a transposon, carrying bla KPC-3 (48, 55.2%), bla KPC-2 (38, 43.7%), and in one case (1.2%) bla KPC-33, the latter gene conferred resistance to ceftazidime/avibactam (CZA). Thirty strains (34.5%) harbored porin mutations; of them, 7 (8.1%) carried multiple Tn4401a copies. These strains were characterized by significantly higher CZA minimum inhibitory concentration compared with strains with no porin mutations or single Tn4401a copy, respectively, even if they did not overcome the resistance breakpoint of 8 ug/mL. Median 2 (IQR:1-2) virulence factors per strain were detected. The lowest number was observed in ST20 compared to the other STs (p<0.001). While ST307 was associated with infection events, a trend associated with colonization events could be observed for ST20., Conclusions: Integration of genomic, resistance score, and clinical data allowed us to define a relative diversification of KPC-Kp in Northern Italy between 2019 and 2021, characterized by few large transmission chains and rare inter-hospital transmission. Our results also provided initial evidence of correlation between KPC-Kp genomic signatures and higher MIC levels to some antimicrobial agents or colonization/infection status, once again underlining WGS's importance in bacterial surveillance., (© 2024. The Author(s).)
Published: 2024
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28. Adverse events during intravenous fosfomycin therapy in a real-life scenario. Risk factors and the potential role of therapeutic drug monitoring.

Author: Biscarini S, Mangioni D, Bobbio C, Mela L, Alagna L, Baldelli S, Blasi F, Canetta C, Ceriotti F, Gori A, Grasselli G, Mariani B, Muscatello A, Cattaneo D, and Bandera A
Subjects: Humans, Female, Male, Retrospective Studies, Middle Aged, Risk Factors, Aged, Administration, Intravenous, Italy, Adult, Tandem Mass Spectrometry, Fosfomycin adverse effects, Fosfomycin administration & dosage, Fosfomycin therapeutic use, Anti-Bacterial Agents adverse effects, Anti-Bacterial Agents administration & dosage, Anti-Bacterial Agents therapeutic use, Drug Monitoring
Abstract: Background: Intravenous fosfomycin (IVFOF) is gaining interest in severe infections. Its use may be limited by adverse events (AEs). Little experience exists on IVFOF therapeutic drug monitoring (TDM) in real-life setting., Patients and Methods: Retrospective study of patients receiving IVFOF for > 48 h at Policlinico Hospital (Milan, Italy) from 01/01/2019 to 01/01/2023. AEs associated to IVFOF graded CTCAE ≥ II were considered. Demographic and clinical risk factors for IVFOF-related AEs were analysed with simple and multivariable regression models. The determination of IVFOF TDM was made by a rapid ultraperformance liquid chromatography mass spectrometry method (LC-MS/MS) on plasma samples. The performance of TDM (trough levels (Cmin) in intermittent infusion, steady state levels (Css) in continuous infusion) in predicting AEs ≤ 5 days after its assessment was evaluated., Results: Two hundred and twenty-four patients were included. At IVFOF initiation, 81/224 (36.2%) patients were in ICU and 35/224 (15.7%) had septic shock. The most frequent infection site was the low respiratory tract (124/224, 55.4%). Ninety-five patients (42.4%) experienced ≥ 1AEs, with median time of 4.0 (2.0-7.0) days from IVFOF initiation. Hypernatremia was the most frequent AE (53/224, 23.7%). Therapy discontinuation due to AEs occurred in 38/224 (17.0%). ICU setting, low respiratory tract infections and septic shock resulted associated with AEs (RR adjusted 1.59 (95%CI:1.09-2.31), 1.46 (95%CI:1.03-2.07) and 1.73 (95%CI:1.27-2.37), respectively), while IVFOF daily dose did not. Of the 68 patients undergone IVFOF TDM, TDM values predicted overall AEs and hypernatremia with AUROC of 0.65 (95%CI:0.44-0.86) and 0.91 (95%CI:0.79-1.0) respectively for Cmin, 0.67 (95%CI:0.39-0.95) and 0.76 (95%CI:0.52-1.0) respectively for Css., Conclusions: We provided real world data on the use of IVFOF-based regimens and associated AEs. IVFOF TDM deserves further research as it may represent a valid tool to predict AEs., Key Points: Real world data on intravenous fosfomycin for severe bacterial infections. AEs occurred in over 40% (therapy discontinuation in 17%) and were related to baseline clinical severity but not to fosfomycin dose. TDM showed promising results in predicting AEs., (© 2024. The Author(s).)
Published: 2024
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29. Correction: Rapid multiplex PCR panels for the management of ventilator-associated pneumonia: pondering strengths and weaknesses.

Author: Tomasello M, Mangioni D, Panigada M, Matinato C, and Bandera A
Published: 2024
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30. Rapid multiplex PCR panels for the management of ventilator-associated pneumonia: pondering strengths and weaknesses.

Author: Tomasello M, Mangioni D, Panigada M, Matinato C, and Bandera A
Subjects: Humans, Pneumonia, Ventilator-Associated diagnosis, Multiplex Polymerase Chain Reaction methods
Published: 2024
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31. New Antibiotics Against Multidrug-Resistant Gram-Negative Bacteria in Liver Transplantation: Clinical Perspectives, Toxicity, and PK/PD Properties.

Author: Lombardi A, Alagna L, Palomba E, Viero G, Tonizzo A, Mangioni D, and Bandera A
Subjects: Humans, beta-Lactamase Inhibitors pharmacology, beta-Lactamase Inhibitors therapeutic use, Drug Resistance, Multiple, Bacterial, Gram-Negative Bacteria, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Liver Transplantation
Abstract: Antimicrobial resistance is a growing global health problem, and it is especially relevant among liver transplant recipients where infections, particularly when caused by microorganisms with a difficult-to-treat profile, are a significant cause of morbidity and mortality. We provide here a complete dissection of the antibiotics active against multidrug-resistant Gram-negative bacteria approved over the last years, focusing on their activity spectrum, toxicity profile and PK/PD properties, including therapeutic drug monitoring, in the setting of liver transplantation. Specifically, the following drugs are presented: ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam, cefiderocol, and eravacycline. Overall, studies on the safety and optimal employment of these drugs in liver transplant recipients are limited and especially needed. Nevertheless, these pharmaceuticals have undeniably enhanced therapeutic options for infected liver transplant recipients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lombardi, Alagna, Palomba, Viero, Tonizzo, Mangioni and Bandera.)
Published: 2024
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32. Increase in invasive group A streptococcal infections in Milan, Italy: a genomic and clinical characterization.

Author: Mangioni D, Fox V, Saltini P, Lombardi A, Bussini L, Carella F, Cariani L, Comelli A, Matinato C, Muscatello A, Teri A, Terranova L, Cento V, Carloni S, Bartoletti M, Alteri C, and Bandera A
Abstract: Background: Group A Streptococcus (GAS) causes multiple clinical manifestations, including invasive (iGAS) or even life-threatening (severe-iGAS) infections. After the drop in cases during COVID-19 pandemic, in 2022 a sharp increase of GAS was reported globally., Methods: GAS strains collected in 09/2022-03/2023 in two university hospitals in Milan, Italy were retrospectively analyzed. Clinical/epidemiological data were combined with whole-genome sequencing to: (i) define resistome/virulome, (ii) identify putative transmission chains, (iii) explore associations between emm- types and clinical severity., Results: Twenty-eight isolates were available, 19/28 (67.9%) from adults and 9/28 (32.1%) from pediatric population. The criteria for iGAS were met by 19/28 cases (67.9%), of which 11/19 (39.3%) met the further criteria for severe-iGAS. Pediatric cases were mainly non-invasive infections (8/9, 88.9%), adult cases were iGAS and severe-iGAS in 18/19 (94.7%) and 10/19 (52.6%), respectively. Thirteen emm -types were detected, the most prevalent being emm 1 and emm 12 (6/28 strains each, 21.4%). Single nucleotide polymorphism (SNP) analysis of emm 1.0 and emm 12.0 strains revealed pairwise SNP distance always >10, inconsistent with unique transmission chains. Emm 12.0-type, found to almost exclusively carry virulence factors spe H and spe I, was mainly detected in children and in no-iGAS infections (55.6 vs. 5.3%, p = 0.007 and 66.7 vs. 0.0%, p < 0.001, respectively), while emm 1.0-type was mainly detected in severe-iGAS (0.0 vs. 45.5%, p = 0.045)., Conclusions: This study showed that multiple emm -types contributed to a 2022/2023 GAS infection increase in two hospitals in Milan, with no evidence of direct transmission chains. Specific emm -types could be associated with disease severity or invasiveness. Overall, these results support the integration of classical epidemiological studies with genomic investigation to appropriately manage severe infections and improve surveillance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Mangioni, Fox, Saltini, Lombardi, Bussini, Carella, Cariani, Comelli, Matinato, Muscatello, Teri, Terranova, Cento, Carloni, Bartoletti, Alteri and Bandera.)
Published: 2024
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33. Incidence, microbiological and immunological characteristics of ventilator-associated pneumonia assessed by bronchoalveolar lavage and endotracheal aspirate in a prospective cohort of COVID-19 patients: CoV-AP study.

Author: Mangioni D, Panigada M, Palomba E, Bobbio C, Chatenoud L, Alagna L, Fumagalli J, Gori A, Grancini A, Guzzardella A, Lombardi A, Matinato C, Meli A, Muscatello A, Porretti L, Tomasello M, Trombetta E, Valenti L, Bandera A, and Grasselli G
Subjects: Humans, Cohort Studies, Incidence, Prospective Studies, Bronchoalveolar Lavage, Dimercaprol, COVID-19 epidemiology, Pneumonia, Ventilator-Associated diagnosis, Pneumonia, Ventilator-Associated epidemiology
Abstract: Background: No univocal recommendation exists for microbiological diagnosis of ventilator-associated pneumonia (VAP). Sampling of either proximal or distal respiratory tract likely impacts on the broad range of VAP incidence between cohorts. Immune biomarkers to rule-in/rule-out VAP diagnosis, although promising, have not yet been validated. COVID-19-induced ARDS made VAP recognition even more challenging, often leading to overdiagnosis and overtreatment. We evaluated the impact of different respiratory samples and laboratory techniques on VAP incidence and microbiological findings in COVID-19 patients., Methods: Prospective single-centre cohort study conducted among COVID-19 mechanically ventilated patients in Policlinico Hospital (Milan, Italy) from January 2021 to May 2022. Microbiological confirmation of suspected VAP (sVAP) was based on concomitant endotracheal aspirates (ETA) and bronchoalveolar lavage (BAL). Conventional and fast microbiology (FILMARRAY® Pneumonia Panel plus, BAL FAPPP ) as well as immunological markers (immune cells and inflammatory cytokines) was analysed., Results: Seventy-nine patients were included. Exposure to antibiotics and steroid therapy before ICU admission occurred in 51/79 (64.6%) and 60/79 (65.9%) patients, respectively. Median duration of MV at VAP suspicion was 6 (5-9) days. Incidence rate of microbiologically confirmed VAP was 33.1 (95% CI 22.1-44.0) and 20.1 (95% CI 12.5-27.7) according to ETA and BAL, respectively. Concordance between ETA and BAL was observed in 35/49 (71.4%) cases, concordance between BAL FAPPP and BAL in 39/49 (79.6%) cases. With BAL as reference standard, ETA showed 88.9% (95% CI 70.8-97.7) sensitivity and 50.0% (95% CI 28.2-71.8) specificity (Cohen's Kappa 0.40, 95% CI 0.16-0.65). BAL FAPPP showed 95.0% (95% CI 75.1-99.9) sensitivity and 69% (95% CI 49.2-84.7) specificity (Cohen's Kappa 0.60, 95% CI 0.39-0.81). BAL IL-1β differed significantly between VAP (135 (IQR 11-450) pg/ml) and no-VAP (10 (IQR 2.9-105) pg/ml) patients (P = 0.03)., Conclusions: In COVID-19 ICU patients, differences in microbial sampling at VAP suspicion could lead to high variability in VAP incidence and microbiological findings. Concordance between ETA and BAL was mainly limited by over 20% of ETA positive and BAL negative samples, while BAL FAPPP showed high sensitivity but limited specificity when evaluating in-panel targets only. These factors should be considered when comparing results of cohorts with different sampling. BAL IL-1β showed potential in discriminating microbiologically confirmed VAP., Clinical Trial Registration: NCT04766983, registered on February 23, 2021., (© 2023. BioMed Central Ltd., part of Springer Nature.)
Published: 2023
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34. Multidrug-Resistant Bacterial Colonization and Infections in Large Retrospective Cohort of Mechanically Ventilated COVID-19 Patients 1 .

Author: Mangioni D, Chatenoud L, Colombo J, Palomba E, Guerrero FA, Bolis M, Bottino N, Breda G, Chiaruttini MV, Fior G, Marotta M, Massobrio G, Matinato C, Muscatello A, Previtali P, Santambrogio S, Tardini F, Zuglian G, Grasselli G, Fumagalli R, Gori A, Stocchetti N, Monti G, and Bandera A
Subjects: Humans, Retrospective Studies, Drug Resistance, Multiple, Bacterial, Respiration, Artificial, Pandemics, COVID-19 epidemiology, Bacterial Infections microbiology
Abstract: Few data are available on incidence of multidrug-resistant organism (MDRO) colonization and infections in mechanically ventilated patients, particularly during the COVID-19 pandemic. We retrospectively evaluated all patients admitted to the COVID-19 intensive care unit (ICU) of Hub Hospital in Milan, Italy, during October 2020‒May 2021. Microbiologic surveillance was standardized with active screening at admission and weekly during ICU stay. Of 435 patients, 88 (20.2%) had MDROs isolated ≤48 h after admission. Of the remaining patients, MDRO colonization was diagnosed in 173 (51.2%), MDRO infections in 95 (28.1%), and non-MDRO infections in 212 (62.7%). Non-MDRO infections occurred earlier than MDRO infections (6 days vs. 10 days; p<0.001). Previous exposure to antimicrobial drugs within the ICU was higher in MDRO patients than in non-MDRO patients (116/197 [58.9%] vs. 18/140 [12.9%]; p<0.001). Our findings might serve as warnings for future respiratory viral pandemics and call for increased measures of antimicrobial stewardship and infection control.
Published: 2023
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35. Genomic Characterization of Carbapenem-Resistant Acinetobacter baumannii (CRAB) in Mechanically Ventilated COVID-19 Patients and Impact of Infection Control Measures on Reducing CRAB Circulation during the Second Wave of the SARS-CoV-2 Pandemic in Milan, Italy.

Author: Mangioni D, Fox V, Chatenoud L, Bolis M, Bottino N, Cariani L, Gentiloni Silverj F, Matinato C, Monti G, Muscatello A, Teri A, Terranova L, Piatti A, Gori A, Grasselli G, Stocchetti N, Alteri C, and Bandera A
Abstract: COVID-19 has significantly affected hospital infection prevention and control (IPC) practices, especially in intensive care units (ICUs). This frequently caused dissemination of multidrug-resistant organisms (MDROs), including carbapenem-resistant Acinetobacter baumannii (CRAB). Here, we report the management of a CRAB outbreak in a large ICU COVID-19 hub Hospital in Italy, together with retrospective genotypic analysis by whole-genome sequencing (WGS). Bacterial strains obtained from severe COVID-19 mechanically ventilated patients diagnosed with CRAB infection or colonization between October 2020 and May 2021 were analyzed by WGS to assess antimicrobial resistance and virulence genes, along with mobile genetic elements. Phylogenetic analysis in combination with epidemiological data was used to identify putative transmission chains. CRAB infections and colonization were diagnosed in 14/40 (35%) and 26/40 (65%) cases, respectively, with isolation within 48 h from admission in 7 cases (17.5%). All CRAB strains belonged to Pasteur sequence type 2 (ST2) and 5 different Oxford STs and presented bla OXA-23 gene-carrying Tn 2006 transposons. Phylogenetic analysis revealed the existence of four transmission chains inside and among ICUs, circulating mainly between November and January 2021. A tailored IPC strategy was composed of a 5-point bundle, including ICU modules' temporary conversion to CRAB-ICUs and dynamic reopening, with limited impact on ICU admission rate. After its implementation, no CRAB transmission chains were detected. Our study underlies the potentiality of integrating classical epidemiological studies with genomic investigation to identify transmission routes during outbreaks, which could represent a valuable tool to ensure IPC strategies and prevent the spread of MDROs. IMPORTANCE Infection prevention and control (IPC) practices are of paramount importance for preventing the spread of multidrug-resistant organisms (MDROs) in hospitals, especially in the intensive care unit (ICU). Whole-genome sequencing (WGS) is seen as a promising tool for IPC, but its employment is currently still limited. COVID-19 pandemics have posed dramatic challenges in IPC practices, causing worldwide several outbreaks of MDROs, including carbapenem-resistant Acinetobacter baumannii (CRAB). We present the management of a CRAB outbreak in a large ICU COVID-19 hub hospital in Italy using a tailored IPC strategy that allowed us to contain CRAB transmission while preventing ICU closure during a critical pandemic period. The analysis of clinical and epidemiological data coupled with retrospective genotypic analysis by WGS identified different putative transmission chains and confirmed the effectiveness of the IPC strategy implemented. This could be a promising approach for future IPC strategies.
Published: 2023
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36. Changes in upper airways microbiota in ventilator-associated pneumonia.

Author: Alagna L, Mancabelli L, Magni F, Chatenoud L, Bassi G, Del Bianco S, Fumagalli R, Turroni F, Mangioni D, Migliorino GM, Milani C, Muscatello A, Nattino G, Picetti E, Pinciroli R, Rossi S, Tonetti T, Vargiolu A, Bandera A, Ventura M, Citerio G, and Gori A
Abstract: Background: The role of upper airways microbiota and its association with ventilator-associated pneumonia (VAP) development in mechanically ventilated (MV) patients is unclear. Taking advantage of data collected in a prospective study aimed to assess the composition and over-time variation of upper airway microbiota in patients MV for non-pulmonary reasons, we describe upper airway microbiota characteristics among VAP and NO-VAP patients., Methods: Exploratory analysis of data collected in a prospective observational study on patients intubated for non-pulmonary conditions. Microbiota analysis (trough 16S-rRNA gene profiling) was performed on endotracheal aspirates (at intubation, T0, and after 72 h, T3) of patients with VAP (cases cohort) and a subgroup of NO-VAP patients (control cohort, matched according to total intubation time)., Results: Samples from 13 VAP patients and 22 NO-VAP matched controls were analyzed. At intubation (T0), patients with VAP revealed a significantly lower microbial complexity of the microbiota of the upper airways compared to NO-VAP controls (alpha diversity index of 84 ± 37 and 160 ± 102, in VAP and NO_VAP group, respectively, p-value < 0.012). Furthermore, an overall decrease in microbial diversity was observed in both groups at T3 as compared to T0. At T3, a loss of some genera (Prevotella 7, Fusobacterium, Neisseria, Escherichia-Shigella and Haemophilus) was found in VAP patients. In contrast, eight genera belonging to the Bacteroidetes, Firmicutes and Fusobacteria phyla was predominant in this group. However, it is unclear whether VAP caused dysbiosis or dysbiosis caused VAP., Conclusions: In a small sample size of intubated patients, microbial diversity at intubation was less in patients with VAP compared to patients without VAP., (© 2023. The Author(s).)
Published: 2023
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37. Plasma Proteomic Variables Related to COVID-19 Severity: An Untargeted nLC-MS/MS Investigation.

Author: Pagani L, Chinello C, Risca G, Capitoli G, Criscuolo L, Lombardi A, Ungaro R, Mangioni D, Piga I, Muscatello A, Blasi F, Favalli A, Martinovic M, Gori A, Bandera A, Grifantini R, and Magni F
Subjects: Humans, Chromatography, Liquid, SARS-CoV-2 pathogenicity, Tandem Mass Spectrometry, COVID-19 diagnosis, COVID-19 metabolism, Proteomics methods, Patient Acuity
Abstract: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection leads to a wide range of clinical manifestations and determines the need for personalized and precision medicine. To better understand the biological determinants of this heterogeneity, we explored the plasma proteome of 43 COVID-19 patients with different outcomes by an untargeted liquid chromatography-mass spectrometry approach. The comparison between asymptomatic or pauci-symptomatic subjects (MILDs), and hospitalised patients in need of oxygen support therapy (SEVEREs) highlighted 29 proteins emerged as differentially expressed: 12 overexpressed in MILDs and 17 in SEVEREs. Moreover, a supervised analysis based on a decision-tree recognised three proteins (Fetuin-A, Ig lambda-2chain-C-region, Vitronectin) that are able to robustly discriminate between the two classes independently from the infection stage. In silico functional annotation of the 29 deregulated proteins pinpointed several functions possibly related to the severity; no pathway was associated exclusively to MILDs, while several only to SEVEREs, and some associated to both MILDs and SEVEREs; SARS-CoV-2 signalling pathway was significantly enriched by proteins up-expressed in SEVEREs ( SAA1/2 , CRP , HP , LRG1 ) and in MILDs ( GSN , HRG ). In conclusion, our analysis could provide key information for 'proteomically' defining possible upstream mechanisms and mediators triggering or limiting the domino effect of the immune-related response and characterizing severe exacerbations.
Published: 2023
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38. Prognostic Value of Mid-Region Proadrenomedullin and In Vitro Interferon Gamma Production for In-Hospital Mortality in Patients with COVID-19 Pneumonia and Respiratory Failure: An Observational Prospective Study.

Author: Mangioni D, Oggioni M, Chatenoud L, Liparoti A, Uceda Renteria S, Alagna L, Biscarini S, Bolis M, Di Modugno A, Mussa M, Renisi G, Ungaro R, Muscatello A, Gori A, Ceriotti F, and Bandera A
Subjects: Adrenomedullin, Adult, Aged, Biomarkers, COVID-19 Vaccines, Female, Hospital Mortality, Humans, Interferon-gamma, Male, Prognosis, Prospective Studies, Protein Precursors, COVID-19, Respiratory Insufficiency
Abstract: Coagulopathy and immune dysregulation have been identified as important causes of adverse outcomes in coronavirus disease (COVID-19). Mid-region proadrenomedullin (MR-proADM) is associated with endothelial damage and has recently been proposed as a prognostic factor in COVID-19. In non-COVID-19 immunocompromised patients, low in vitro interferon gamma (IFNγ) production correlates with infection risk and mortality. This prospective, monocentric, observational study included adult patients consecutively admitted with radiologic evidence of COVID-19 pneumonia and respiratory failure. MR-proADM and in vitro IFNγ production were measured at T0 (day 1 from admission) and T1 (day 7 from enrollment). One hundred patients were enrolled. Thirty-six percent were females, median age 65 (Q1−Q3 54.5−75) years, and 58% had ≥1 comorbidity. Only 16 patients had received COVID-19 vaccination before hospitalization. At admission, the median PaO2:FiO2 ratio was 241 (157−309) mmHg. In-hospital mortality was 13%. MR-proADM levels differed significantly between deceased and survivors both at T0 (1.41 (1.12−1.77) nmol/L vs. 0.79 (0.63−1.03) nmol/L, p < 0.001) and T1 (1.67 (1.08−1.96) nmol/L vs. 0.66 (0.53−0.95) nmol/L, p < 0.001). In vitro IFNγ production at T0 and T1 did not vary between groups. When only the subset of non-vaccinated patients was considered, both biomarkers at T1 resulted significantly associated with in-hospital mortality. AUROC for MR-proADM at T0 to predict in-hospital mortality was 0.87 (95%CI 0.79−0.94), with the best cut-off point at 1.04 nmol/L (92% sensitivity, 75% specificity and 98% negative predictive value). In patients with COVID-19 pneumonia and different degrees of respiratory failure, MR-proADM at admission and during hospitalization resulted strongly associated with in-hospital mortality. Low in vitro IFNγ production after the first week of hospitalization was associated with mortality in non-vaccinated patients possibly identifying the subgroup characterized by a higher degree of immune suppression.
Published: 2022
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39. Immunogenicity and effectiveness of BNT162b2 COVID-19 vaccine in a cohort of healthcare workers in Milan (Lombardy Region, Northern Italy).

Author: Consonni D, Lombardi A, Mangioni D, Bono P, Oggioni M, Uceda Renteria S, Valzano A, Bordini L, Nava CD, Tiwana N, Gentiloni Silverj F, Castaldi S, Rognoni M, Cavalieri D'Oro L, Carugno M, Luisetti G, Riboldi L, Ceriotti F, Bandera A, Gori A, and Pesatori AC
Subjects: Humans, Cohort Studies, COVID-19 Vaccines, Italy epidemiology, SARS-CoV-2, Health Personnel, BNT162 Vaccine, COVID-19 epidemiology, COVID-19 prevention & control
Abstract: Objectives: to evaluate immunogenicity and effectiveness of BNT162b2 COVID-19 vaccine in a cohort of healthcare workers (HCWs)., Design: cohort study., Setting and Participants: in a hospital in Milan (Lombardy Region, Northern Italy) HCWs without ("negative cohort") and with ("positive cohort") history of SARS-CoV-2 infection or elevated serum antibody before the vaccination campaign (27.12.2020) were included. Data collection and follow-up covered the period 27.12.2020-13.05.2022., Main Outcomes Measures: 1. serum anti-spike-1 (anti-S1) antibody levels after vaccination; 2. vaccine effectiveness (VE) against SARS-CoV-2 infections (either symptomatic or not) in the negative cohort. Data on infections were extracted from multiple sources (laboratory, accident reports, questionnaires). Vaccination was treated as a time-dependent variable. Using unvaccinated person-time as reference, hazard ratios (HR) of infections and 95% confidence intervals (95%CI) were calculated with a Cox regression model adjusted for gender, age, and occupation. VE was calculated as (1 - HR)×100., Results: 5,596 HCWs were included, 4,771 in the negative and 825 in the positive cohort. In both cohorts, serum anti-S1 antibodies were high one months after the second dose, halved after six months, and returned to high levels after the third dose. In the negative cohort, 1,401 SARS-CoV-2 infections were identified. VE was 70% (95%CI 54-80; 46 infected) in the first four months after the second dose and later declined to 16% (95%CI 0-43; 97 infected). After the third dose, VE increased to 57% (95%CI 35-71; 61 infected) in the first month but rapidly declined over time, particularly after three months (24% in the fourth month and 1% afterwards). The number of infections avoided by vaccination was estimated to be 643 (95%CI 236-1,237)., Conclusions: in spite of rapidly declining effectiveness, vaccination helped to avoid several hundred infections in the considered hospital.
Published: 2022
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40. Fosfomycin therapeutic drug monitoring in real-life: development and validation of a LC-MS/MS method on plasma samples.

Author: Baldelli S, Cerea M, Mangioni D, Alagna L, Muscatello A, Bandera A, and Cattaneo D
Subjects: Anti-Bacterial Agents administration & dosage, Anti-Bacterial Agents adverse effects, Chromatography, High Pressure Liquid, Fosfomycin administration & dosage, Fosfomycin adverse effects, Humans, Tandem Mass Spectrometry, Time Factors, Anti-Bacterial Agents blood, Drug Monitoring methods, Fosfomycin blood
Abstract: Individualization of fosfomycin dosing based on therapeutic drug monitoring (TDM) of plasma concentrations could reduce drug-related adverse events and improve clinical outcome in complex clinical conditions. Quantification of fosfomycin in plasma samples was performed by a rapid ultraperformance liquid chromatography mass spectrometry method. Sample preparation involved protein precipitation with [ 13 C 3 ]-fosfomycin benzylamine salt as internal standard. The calibration curve ranged from 2 to 800 mg/L. Within- and between-day precision and accuracy, sensitivity, selectivity, dilution integrity, recovery were investigated and the results met the acceptance criteria. In patients, multiple drug dosing (every 6 or 8 hours) or in continuous administration were adopted, resulting in a large interpatient variability in drug concentrations (from 7.4 mg/L and 644.6 mg/L; CV: 91.1%). In critical care patient setting TDM can represent an important tool to identify the best fosfomycin dosing in single patients, taking into consideration clinical characteristics, infection sites and susceptibility of the treated pathogens.
Published: 2022
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41. Strongyloides stercoralis central nervous system dissemination in a migrant misdiagnosed with eosinophilic granulomatosis with polyangiitis.

Author: Comelli A, Mangioni D, Scaramella L, Maraschini A, Gaudino C, Folli C, Ceriotti F, Triulzi F, Canetta C, Gori A, and Bandera A
Subjects: Animals, Central Nervous System, Diagnostic Errors, Humans, Churg-Strauss Syndrome, Granulomatosis with Polyangiitis, Strongyloides stercoralis, Strongyloidiasis diagnosis, Strongyloidiasis drug therapy, Transients and Migrants
Published: 2022
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42. Exosomes Recovered From the Plasma of COVID-19 Patients Expose SARS-CoV-2 Spike-Derived Fragments and Contribute to the Adaptive Immune Response.

Author: Pesce E, Manfrini N, Cordiglieri C, Santi S, Bandera A, Gobbini A, Gruarin P, Favalli A, Bombaci M, Cuomo A, Collino F, Cricrì G, Ungaro R, Lombardi A, Mangioni D, Muscatello A, Aliberti S, Blasi F, Gori A, Abrignani S, De Francesco R, Biffo S, and Grifantini R
Subjects: Acute Disease, Adult, Aged, COVID-19 blood, Exosomes metabolism, Female, Humans, Male, Middle Aged, Plasma, SARS-CoV-2 metabolism, Spike Glycoprotein, Coronavirus blood, Adaptive Immunity, COVID-19 immunology, Exosomes immunology, SARS-CoV-2 immunology, Spike Glycoprotein, Coronavirus immunology
Abstract: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by beta-coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has rapidly spread across the globe starting from February 2020. It is well established that during viral infection, extracellular vesicles become delivery/presenting vectors of viral material. However, studies regarding extracellular vesicle function in COVID-19 pathology are still scanty. Here, we performed a comparative study on exosomes recovered from the plasma of either MILD or SEVERE COVID-19 patients. We show that although both types of vesicles efficiently display SARS-CoV-2 spike-derived peptides and carry immunomodulatory molecules, only those of MILD patients are capable of efficiently regulating antigen-specific CD4 + T-cell responses. Accordingly, by mass spectrometry, we show that the proteome of exosomes of MILD patients correlates with a proper functioning of the immune system, while that of SEVERE patients is associated with increased and chronic inflammation. Overall, we show that exosomes recovered from the plasma of COVID-19 patients possess SARS-CoV-2-derived protein material, have an active role in enhancing the immune response, and possess a cargo that reflects the pathological state of patients in the acute phase of the disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pesce, Manfrini, Cordiglieri, Santi, Bandera, Gobbini, Gruarin, Favalli, Bombaci, Cuomo, Collino, Cricrì, Ungaro, Lombardi, Mangioni, Muscatello, Aliberti, Blasi, Gori, Abrignani, De Francesco, Biffo and Grifantini.)
Published: 2022
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43. Side effects among healthcare workers from a large Milan university hospital after second dose of BNT162b2 mRNA COVID-19 vaccine.

Author: Borroni E, Consonni D, Cugno M, Lombardi A, Mangioni D, Bono P, Oggioni M, Uceda Renteria S, Bordini L, Nava CD, Letzgus M, Gentiloni Silverj F, Castaldi S, Rognoni M, Cavallieri D'Oro L, Carugno M, Riboldi L, Ceriotti F, Bandera A, Gori A, and Pesatori AC
Subjects: Adult, BNT162 Vaccine, Female, Health Personnel, Hospitals, Humans, RNA, Messenger, SARS-CoV-2, COVID-19, COVID-19 Vaccines
Abstract: Background: In Italy, healthcare workers (HCWs) were among the first to receive COVID-19 vaccination. Aim of the present study is to evaluate frequency and severity of adverse events (AEs) following the second dose of BNT162b2 vaccine among HCWs of a large university hospital in Milan, Italy., Methods: One month after having received the second dose of vaccine, HCWs filled-in a form about type, severity, and duration of post-vaccination local and systemic symptoms. We calculated the overall frequency of AEs and used multivariable Poisson regression models (adjusted for sex, age, BMI, smoking, allergy history, previous SARS-CoV-2 infection, anti-hypertensive therapy, and occupation) to calculate risk ratios (RR) and 95% confidence intervals (CI) of AEs according to selected variables., Results: We included 3659 HCWs. Overall, 2801 (76.6%) experienced at least one local event, with pain at injection site being the most frequent (2788, 76.2%). Systemic events were reported by 2080 (56.8%) HCWs, with fatigue (52.3%), muscle pain (42.2%), headache (37.7%), joint pain (31.9%), and fever (26.2%) being the most frequent. Risks of systemic events were associated with female gender (RR=1.14, CI: 1.06-1.23), age (strong decrease with increasing age, p-trend<0.001), allergy history (RR=1.13, CI: 1.05-1.20), and current smoking (RR=0.90, CI: 0.84-0.97). HCWs with previous SARS-CoV-2 infection (even if symptomatic) were not at increased risk., Conclusions: Both local and systemic acute effects after second dose of BNT162b2 vaccine were frequently reported. However, symptoms were mostly light/mild and of short duration. Thus, our findings support the safety of COVID-19 vaccination in adults in relatively good health.
Published: 2021
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44. Effect of anakinra on mortality in patients with COVID-19: a systematic review and patient-level meta-analysis.

Author: Kyriazopoulou E, Huet T, Cavalli G, Gori A, Kyprianou M, Pickkers P, Eugen-Olsen J, Clerici M, Veas F, Chatellier G, Kaplanski G, Netea MG, Pontali E, Gattorno M, Cauchois R, Kooistra E, Kox M, Bandera A, Beaussier H, Mangioni D, Dagna L, van der Meer JWM, Giamarellos-Bourboulis EJ, and Hayem G
Abstract: Background: Anakinra might improve the prognosis of patients with moderate to severe COVID-19 (ie, patients requiring oxygen supplementation but not yet receiving organ support). We aimed to assess the effect of anakinra treatment on mortality in patients admitted to hospital with COVID-19., Methods: For this systematic review and individual patient-level meta-analysis, a systematic literature search was done on Dec 28, 2020, in Medline (PubMed), Cochrane, medRxiv, bioRxiv, and the ClinicalTrials.gov databases for randomised trials, comparative studies, and observational studies of patients admitted to hospital with COVID-19, comparing administration of anakinra with standard of care, or placebo, or both. The search was repeated on Jan 22, 2021. Individual patient-level data were requested from investigators and corresponding authors of eligible studies; if individual patient-level data were not available, published data were extracted from the original reports. The primary endpoint was mortality after 28 days and the secondary endpoint was safety (eg, the risk of secondary infections). This study is registered on PROSPERO (CRD42020221491)., Findings: 209 articles were identified, of which 178 full-text articles fulfilled screening criteria and were assessed. Aggregate data on 1185 patients from nine studies were analysed, and individual patient-level data on 895 patients were provided from six of these studies. Eight studies were observational and one was a randomised controlled trial. Most studies used historical controls. In the individual patient-level meta-analysis, after adjusting for age, comorbidities, baseline ratio of the arterial partial oxygen pressure divided by the fraction of inspired oxygen (PaO 2 /FiO 2 ), C-reactive protein (CRP) concentrations, and lymphopenia, mortality was significantly lower in patients treated with anakinra (38 [11%] of 342) than in those receiving standard of care with or without placebo (137 [25%] of 553; adjusted odds ratio [OR] 0·32 [95% CI 0·20-0·51]). The mortality benefit was similar across subgroups regardless of comorbidities (ie, diabetes), ferritin concentrations, or the baseline PaO 2 /FiO 2 . In a subgroup analysis, anakinra was more effective in lowering mortality in patients with CRP concentrations higher than 100 mg/L (OR 0·28 [95% CI 0·17-0·47]). Anakinra showed a significant survival benefit when given without dexamethasone (OR 0·23 [95% CI 0·12-0·43]), but not with dexamethasone co-administration (0·72 [95% CI 0·37-1·41]). Anakinra was not associated with a significantly increased risk of secondary infections when compared with standard of care (OR 1·35 [95% CI 0·59-3·10])., Interpretation: Anakinra could be a safe, anti-inflammatory treatment option to reduce the mortality risk in patients admitted to hospital with moderate to severe COVID-19 pneumonia, especially in the presence of signs of hyperinflammation such as CRP concentrations higher than 100 mg/L., Funding: Sobi., Competing Interests: EJG-B has received honoraria from AbbVie USA, Abbott CH, Biotest Germany, Brahms, InflaRx, MSD Greece, XBiotech, and Angelini Italy; independent educational grants from AbbVie, Abbott CH, Astellas Pharma Europe, AxisShield, bioMérieux, InflaRx, the Medicines Company and XBiotech; and funding from the FrameWork 7 program HemoSpec (granted to the National and Kapodistrian University of Athens), the Horizon2020 Marie-Curie Project European Sepsis Academy (granted to the National and Kapodistrian University of Athens), and the Horizon 2020 European Grant ImmunoSep (granted to the Hellenic Institute for the Study of Sepsis). MG has received speakers' fees and unrestricted grants from Novartis and Sobi. PP, MKo, and EKo are funded by a COVID-19 grant paid to the Radboud University Medical Center (Radboudumc). JE-O is a co-founder, shareholder, and CSO of ViroGates, Denmark, and named inventor on patents on suPAR owned by Copenhagen University Hospital Hvidovre, Denmark. GK has received from ROCHE-CHUGAI Research Grants (<€20 000), fees from Sobi France for scientific presentations (<€4000) and participated in a SOBI Advisory Board on COVID (unpaid) and in an OLATEC Monitoring Board (unpaid). GCa has received speakers' and consulting fees from Novartis and Sobi. LD has received grants (paid to LD's institution outside the current work) from AbbVie, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Kiniksa, Merk Sharp & Dohme, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi Genzyme, and Sobi; and consulting fees from AbbVie, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Galapagos, GlaxoSmithKline, Kiniksa, Novartis, Pfizer, Roche, Sanofi-Genzyme, and Sobi. GH reports consultancy fees from Bristol-Myers Squibb, Lilly, Novartis; speakers' fees from AbbVie, Bristol-Myers-Squibb, Celgene, Lilly, Novartis, Pfizer, Roche, Sanofi-Aventis; support for attending meetings from Bristol-Myers-Squibb, Fresenius-Kabi, Janssen-Cilag, Lilly, Mylan, Roche, UCB; and participation on advisory boards for Bristol-Myers-Squibb and Lilly. FV has received (via the Institut de Recherche pour le Développement) Horizon 2020-EDCTP-European Grants: PANDORA and ITAIL-COVID. All other authors declare no competing interests., (© 2021 Elsevier Ltd. All rights reserved.)
Published: 2021
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45. Response.

Author: Grasselli G, Scaravilli V, Mangioni D, Scudeller L, Alagna L, Gori A, and Bandera A
Published: 2021
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46. Immune Checkpoint Inhibitors in People Living with HIV/AIDS: Facts and Controversies.

Author: Castelli V, Lombardi A, Palomba E, Bozzi G, Ungaro R, Alagna L, Mangioni D, Muscatello A, Bandera A, and Gori A
Subjects: Animals, Humans, Neoplasms virology, HIV Infections drug therapy, Immune Checkpoint Inhibitors pharmacology, Neoplasms drug therapy, T-Lymphocytes drug effects
Abstract: Immune checkpoint inhibitors (ICIs) are reshaping the landscape of cancer treatment, redefining the prognosis of several tumors. They act by restoring the cytotoxic activity of tumor-specific T lymphocytes that are in a condition of immune exhaustion. The same condition has been widely described in chronic HIV infection. In this review, we dissect the role of ICIs in people living with HIV/AIDS (PLWHIV). First, we provide an overview of the immunologic scenario. Second, we discuss the possible use of ICIs as adjuvant treatment of HIV to achieve elimination of the viral reservoir. Third, we examine the influence of HIV infection on ICI safety and effectiveness. Finally, we describe how the administration of ICIs impacts opportunistic infections.
Published: 2021
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47. Nasopharyngeal Testing among Healthcare Workers (HCWs) of a Large University Hospital in Milan, Italy during Two Epidemic Waves of COVID-19.

Author: Comelli A, Consonni D, Lombardi A, Viero G, Oggioni M, Bono P, Uceda Renteria SC, Ceriotti F, Mangioni D, Muscatello A, Piatti A, Pesatori AC, Castaldi S, Riboldi L, Bandera A, and Gori A
Subjects: Health Personnel, Hospitals, University, Humans, Italy epidemiology, RNA, Viral, SARS-CoV-2, COVID-19, Epidemics
Abstract: Background: since October 2020, a second SARS-CoV-2 epidemic wave has hit Italy. We investigate the frequency of positive nasopharyngeal swabs among HCWs during the two waves and the association with occupation and demographic characteristics., Methods: this is a retrospective, observational study conducted in a large university hospital in Milan, Northern Italy. We defined two epidemic waves: 1st (February 2020-July 2020) and 2nd (August 2020-January 2021). Occupational and demographic characteristics of HCWs who underwent nasopharyngeal swabs for SARS-CoV-2 were collected., Results: in the 1st wave, 242 positive subjects (7.2%) were found among 3378 HCWs, whereas in the 2nd wave, the positive subjects were 545 out of 4465 (12.2%). In both epidemic waves positive NPSs were more frequent among HCWs with health-related tasks and lower among students ( p < 0.001). However, in the 2nd wave, workers engaged in non-health-related tasks had a peak of 20.7% positivity. Among 160 positive HCWs in the 1st wave who were tested again in the 2nd wave, the rate of reinfection based on SARS-CoV2 RNA cycle quantification value was 0.6%., Conclusions: during the 2nd epidemic wave, we confirmed a significant impact of COVID-19 among HCWs. The rise of infection rate among HCWs seems to reflect the increasing spread of SARS-CoV-2 among the overall population.
Published: 2021
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48. Integrated longitudinal immunophenotypic, transcriptional and repertoire analyses delineate immune responses in COVID-19 patients.

Author: Notarbartolo S, Ranzani V, Bandera A, Gruarin P, Bevilacqua V, Putignano AR, Gobbini A, Galeota E, Manara C, Bombaci M, Pesce E, Zagato E, Favalli A, Sarnicola ML, Curti S, Crosti M, Martinovic M, Fabbris T, Marini F, Donnici L, Lorenzo M, Mancino M, Ungaro R, Lombardi A, Mangioni D, Muscatello A, Aliberti S, Blasi F, De Feo T, Prati D, Manganaro L, Granucci F, Lanzavecchia A, De Francesco R, Gori A, Grifantini R, and Abrignani S
Subjects: Adult, Aged, Antibodies, Viral immunology, B-Lymphocytes immunology, B-Lymphocytes metabolism, Biomarkers, COVID-19 virology, Cell Plasticity genetics, Cell Plasticity immunology, Clonal Evolution immunology, Female, Gene Expression Profiling, Humans, Immunoglobulin Isotypes immunology, Immunologic Memory, Leukocytes, Mononuclear immunology, Leukocytes, Mononuclear metabolism, Lymphocyte Count, Male, Middle Aged, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, COVID-19 genetics, COVID-19 immunology, Host-Pathogen Interactions immunology, Immunophenotyping, SARS-CoV-2 immunology, Transcriptome
Abstract: To understand how a protective immune response against SARS-CoV-2 develops over time, we integrated phenotypic, transcriptional and repertoire analyses on PBMCs from mild and severe COVID-19 patients during and after infection, and compared them to healthy donors (HD). A type I IFN-response signature marked all the immune populations from severe patients during the infection. Humoral immunity was dominated by IgG production primarily against the RBD and N proteins, with neutralizing antibody titers increasing post infection and with disease severity. Memory B cells, including an atypical FCRL5 + T-BET + memory subset, increased during the infection, especially in patients with mild disease. A significant reduction of effector memory, CD8 + T cells frequency characterized patients with severe disease. Despite such impairment, we observed robust clonal expansion of CD8 + T lymphocytes, while CD4 + T cells were less expanded and skewed toward T CM and T H 2-like phenotypes. MAIT cells were also expanded, but only in patients with mild disease. Terminally differentiated CD8 + GZMB + effector cells were clonally expanded both during the infection and post-infection, while CD8 + GZMK + lymphocytes were more expanded post-infection and represented bona fide memory precursor effector cells. TCR repertoire analysis revealed that only highly proliferating T cell clonotypes, which included SARS-CoV-2-specific cells, were maintained post-infection and shared between the CD8 + GZMB + and GZMK + subsets. Overall, this study describes the development of immunity against SARS-CoV-2 and identifies an effector CD8 + T cell population with memory precursor-like features., (Copyright © 2021, American Association for the Advancement of Science.)
Published: 2021
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49. Hospital-Acquired Infections in Critically Ill Patients With COVID-19.

Author: Grasselli G, Scaravilli V, Mangioni D, Scudeller L, Alagna L, Bartoletti M, Bellani G, Biagioni E, Bonfanti P, Bottino N, Coloretti I, Cutuli SL, De Pascale G, Ferlicca D, Fior G, Forastieri A, Franzetti M, Greco M, Guzzardella A, Linguadoca S, Meschiari M, Messina A, Monti G, Morelli P, Muscatello A, Redaelli S, Stefanini F, Tonetti T, Antonelli M, Cecconi M, Foti G, Fumagalli R, Girardis M, Ranieri M, Viale P, Raviglione M, Pesenti A, Gori A, and Bandera A
Subjects: Aged, Critical Illness, Cross Infection epidemiology, Female, Humans, Male, Middle Aged, Pneumonia, Ventilator-Associated complications, Pneumonia, Ventilator-Associated epidemiology, Retrospective Studies, Sepsis complications, Sepsis epidemiology, COVID-19 complications, Cross Infection complications
Abstract: Background: Few small studies have described hospital-acquired infections (HAIs) occurring in patients with COVID-19., Research Question: What characteristics in critically ill patients with COVID-19 are associated with HAIs and how are HAIs associated with outcomes in these patients?, Study Design and Methods: Multicenter retrospective analysis of prospectively collected data including adult patients with severe COVID-19 admitted to eight Italian hub hospitals from February 20, 2020, through May 20, 2020. Descriptive statistics and univariate and multivariate Weibull regression models were used to assess incidence, microbial cause, resistance patterns, risk factors (ie, demographics, comorbidities, exposure to medication), and impact on outcomes (ie, ICU discharge, length of ICU and hospital stays, and duration of mechanical ventilation) of microbiologically confirmed HAIs., Results: Of the 774 included patients, 359 patients (46%) demonstrated 759 HAIs (44.7 infections/1,000 ICU patient-days; 35% multidrug-resistant [MDR] bacteria). Ventilator-associated pneumonia (VAP; n = 389 [50%]), bloodstream infections (BSIs; n = 183 [34%]), and catheter-related BSIs (n = 74 [10%]) were the most frequent HAIs, with 26.0 (95% CI, 23.6-28.8) VAPs per 1,000 intubation-days, 11.7 (95% CI, 10.1-13.5) BSIs per 1,000 ICU patient-days, and 4.7 (95% CI, 3.8-5.9) catheter-related BSIs per 1,000 ICU patient-days. Gram-negative bacteria (especially Enterobacterales) and Staphylococcus aureus caused 64% and 28% of cases of VAP, respectively. Variables independently associated with infection were age, positive end expiratory pressure, and treatment with broad-spectrum antibiotics at admission. Two hundred thirty-four patients (30%) died in the ICU (15.3 deaths/1,000 ICU patient-days). Patients with HAIs complicated by septic shock showed an almost doubled mortality rate (52% vs 29%), whereas noncomplicated infections did not affect mortality. HAIs prolonged mechanical ventilation (median, 24 days [interquartile range (IQR), 14-39 days] vs 9 days [IQR, 5-13 days]; P < .001), ICU stay (24 days [IQR, 16-41 days] vs 9 days [IQR, 6-14 days]; P = .003), and hospital stay (42 days [IQR, 25-59 days] vs 23 days [IQR, 13-34 days]; P < .001)., Interpretation: Critically ill patients with COVID-19 are at high risk for HAIs, especially VAPs and BSIs resulting from MDR organisms. HAIs prolong mechanical ventilation and hospitalization, and HAIs complicated by septic shock almost double mortality., Trial Registry: ClinicalTrials.gov; No.: NCT04388670; URL: www.clinicaltrials.gov., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)
Published: 2021
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50. Fecal Microbiota Transplant: Keep Calm and Carry On, Learning From Experience.

Author: Mangioni D, Alagna L, Gori A, and Bandera A
Subjects: Fecal Microbiota Transplantation, Gram-Negative Bacteria, Humans, Bacteremia, Gastrointestinal Microbiome, Microbiota
Published: 2021
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