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1. 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

2. 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

3. 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

4. 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

5. 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
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6. Higher levels of IgA and IgG at sepsis onset are associated with higher mortality: results from the Albumin Italian Outcome Sepsis (ALBIOS) trial

Author

Walter Taccone, Andrea Cortegiani, Irene Principale, Pietro Caironi, Roberto Latini, Barbara Bottazzi, Francesca Motta, Laura Alagna, Fabio Silvio Taccone, Giacomo Grasselli, Luigi Vivona, Alessandra Bandera, Nicolò M Agnelli, Francesca Di Marzo Capozzi, Jennifer Meessen, Roberto Keim, Vieri Parrini, Giacomo Bellani, Daniela Albiero, Stefano Romagnoli, Alagna, L, Meessen, J, Bellani, G, Albiero, D, Caironi, P, Principale, I, Vivona, L, Grasselli, G, Motta, F, Agnelli, N, Parrini, V, Romagnoli, S, Keim, R, Di Marzo Capozzi, F, Taccone, F, Taccone, W, Bottazzi, B, Bandera, A, Cortegiani, A, Latini, R, Alagna, Laura, Meessen, Jennifer M T A, Bellani, Giacomo, Albiero, Daniela, Caironi, Pietro, Principale, Irene, Vivona, Luigi, Grasselli, Giacomo, Motta, Francesca, Agnelli, Nicolò M, Parrini, Vieri, Romagnoli, Stefano, Keim, Roberto, Di Marzo Capozzi, Francesca, Taccone, Fabio S, Taccone, Walter, Bottazzi, Barbara, Bandera, Alessandra, Cortegiani, Andrea, and Latini, Roberto

Subjects
medicine.medical_specialty, Sepsi, IgG, Secondary infection, Critical Care and Intensive Care Medicine, Gastroenterology, law.invention, Sepsis, Randomized controlled trial, law, Internal medicine, Septic shock, Risk of mortality, medicine, Clinical significance, Mortality, business.industry, RC86-88.9, Research, Medical emergencies. Critical care. Intensive care. First aid, Venous blood, medicine.disease, IgM Immunoglobulins, business, IgA, IgM Immunoglobulin, Cohort study
Abstract

Background The role of intravenous immunoglobulins (IVIG) during sepsis is controversial, as different trials on IVIG have observed inconsistent survival benefits. We aimed to elucidate the possible association and clinical significance between circulating levels of immunoglobulins. Methods In a subset of 956 patients with severe sepsis and septic shock of the multicentre, open-label RCT ALBIOS, venous blood samples were serially collected 1, 2, and 7 days after enrolment (or at ICU discharge, whichever came first). IgA, IgG and IgM concentrations were assayed in all patients on day 1 and in a subgroup of 150 patients on days 2 and 7. Ig concentrations were measured employing a turbidimetric assay, OSR61171 system. Results IgA on day 1 had a significant predictive value for both 28-day and 90-day mortality (28-day mortality, HR: 1.50 (95% CI 1.18–1.92); 90-day mortality, HR: 1.54 (95% CI 1.25–1.91)). IgG, but not IgM, on day 1 showed similar results for 28-day (HR 1.83 (95% CI 1.33–2.51) and 90-day mortality HR: 1.66 (95% CI 1.23–2.25)). In addition, lower levels of IgG but not of IgA and IgM, at day 1 were associated with significantly higher risk of secondary infections (533 [406–772] vs 600 [452–842] mg/dL, median [Q1–Q3], p = 0.007). Conclusions In the largest cohort study of patients with severe sepsis or septic shock, we found that high levels of IgA and IgG on the first day of diagnosis were associated with a decreased 90-day survival. No association was found between IgM levels and survival. As such, the assessment of endogenous immunoglobulins could be a useful tool to identify septic patients at high risk of mortality. Trial registration #NCT00707122, Clinicaltrial.gov, registered 30 June 2008

Published
2021

7. Combination Antifungal Therapy for Invasive Mold Infections Among Pediatric Patients with Hematological Malignancies: Data from A Real-Life Case-Series

Author

Benedetta Longhi, Andrea Gori, Alessandra Bandera, Attilio Rovelli, Laura Alagna, Guglielmo Migliorino, Antonella Colombini, Carmelo Rizzari, Sergio Foresti, Stefano Biffi, Anna Maria Peri, Marta Verna, Peri, A, Verna, M, Biffi, S, Alagna, L, Longhi, B, Migliorino, G, Foresti, S, Bandera, A, Rovelli, A, Rizzari, C, Gori, A, and Colombini, A

Subjects
lcsh:Immunologic diseases. Allergy, Microbiology (medical), Antifungal, Posaconazole, Treatment response, medicine.medical_specialty, medicine.drug_class, Immunology, chemistry.chemical_compound, Internal medicine, lcsh:Pathology, Immunology and Allergy, Medicine, hematological malignancies, Antifungal therapy, Molecular Biology, Voriconazole, business.industry, Medical record, Clinical course, Discontinuation, Infectious Diseases, chemistry, Mold, Hematological malignancie, Caspofungin, lcsh:RC581-607, business, Research Article, lcsh:RB1-214, medicine.drug
Abstract

Background: Invasive mold infections in children with hematological malignancies are associated with high mortality rates. The use of combination antifungal therapy in cases with a severe clinical course is increasing, although information on the efficacy and safety of this approach is limited. Methods: We present a case series of 13 children affected by hemato-oncological disorders who received combination antifungal therapy for invasive mold infections at our center (Pediatric Hematology, San Gerardo Hospital, Monza, Italy) from 2011 to 2016, with the aim of describing their clinical characteristics, types of infections, treatment regimens, clinical outcomes, and treatment safety. Medical records were retrospectively reviewed in order to describe patients’ characteristics. Results: Combination antifungal therapy included liposomal amphotericin associated with caspofungin (5/13, 38.4%), voriconazole (5/13, 38.4%), or posaconazole (3/13, 23.1%). The 12-week treatment response rate was 69.2% (6/13 patients showed complete response, 3/13 partial response). The crude mortality was 30.7% (4/13): half was related to invasive mold infections (2/13, 15.38%) and half to disease progression (2/13, 15.38%). Overall, treatment was well tolerated, and we did not observe any permanent discontinuation of antifungals due to related side effects. Conclusions: In our experience, combination antifungal therapy seems to be a safe option in immunocompromised children with invasive mold infections. Well-designed studies are needed to confirm the safety of this approach and to better understand its efficacy in the pediatric setting. Keywords: antifungal therapy; mold; hematological malignancies

Published
2019
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