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2. Progression Of Atherosclerotic Plaque Determined By Computed Tomography Angiography: A Practical CCTA-based SCORE

Author

Volpe, A., primary, Mushtaq, S., additional, Baggiano, A., additional, Annoni, A., additional, Carerj, M., additional, Cilia, F., additional, Fazzari, F., additional, Formenti, A., additional, Fusini, L., additional, Mancini, M., additional, Marchetti, F., additional, Maragna, R., additional, Tassetti, L., additional, Rossi, A., additional, and Pontone, G., additional

Published
2024
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3. Stress Computed Tomography Perfusion Versus Stress Cardiac Magnetic Resonance For The Management Of Suspected Or Known Coronary Arterydisease: Resources And Outcomes Impact (Strategy II Study)

Author

Baggiano, A., primary, Maragna, R., additional, Guglielmo, M., additional, Mushtaq, S., additional, Annoni, A., additional, Formenti, A., additional, Mancini, M., additional, Fusini, L., additional, Volpe, A., additional, Tassetti, L., additional, Marchetti, F., additional, Junod, D., additional, Fazzari, F., additional, Cannata, F., additional, Del Torto, A., additional, Guaricci, A., additional, and Pontone, G., additional

Published
2024
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4. Does the AVNeo valve reduce wall stress on the aortic wall? A cardiac magnetic resonance analysis with 4D-flow for the evaluation of aortic valve replacement with the Ozaki technique

Author

Pirola, S, Mastroiacovo, G, Bonomi, A, Manchester, E, Fisichella, S, Maragna, R, Baggiano, A, Mushtaq, S, Muscogiuri, G, Guglielmo, M, Xu, X, Pontone, G, Polvani, G, Pirola S., Mastroiacovo G., Bonomi A., Manchester E. L., Fisichella S. M., Maragna R., Baggiano A., Mushtaq S., Muscogiuri G., Guglielmo M., Xu X. Y., Pontone G., Polvani G., Pirola, S, Mastroiacovo, G, Bonomi, A, Manchester, E, Fisichella, S, Maragna, R, Baggiano, A, Mushtaq, S, Muscogiuri, G, Guglielmo, M, Xu, X, Pontone, G, Polvani, G, Pirola S., Mastroiacovo G., Bonomi A., Manchester E. L., Fisichella S. M., Maragna R., Baggiano A., Mushtaq S., Muscogiuri G., Guglielmo M., Xu X. Y., Pontone G., and Polvani G.

Abstract

OBJECTIVES: Aortic valve neocuspidalization aims to replace the 3 aortic cusps with autologous pericardium pre-treated with glutaraldehyde, and it is a surgical alternative to the classical aortic valve replacement (AVR). Image-based patient-specific computational fluid dynamics allows the derivation of shear stress on the aortic wall [wall shear stress (WSS)]. Previous studies support a potential link between increased WSS and histological alterations of the aortic wall. The aim of this study is to compare the WSS of the ascending aorta in patients undergoing aortic valve neocuspidalization versus AVR with biological prostheses. METHODS: This is a prospective nonrandomized clinical trial. Each patient underwent a 4D-flow cardiac magnetic resonance scan after surgery, which informed patient-specific computational fluid dynamics models to evaluate WSS at the ascending aortic wall. The adjusted variables were calculated by summing the residuals obtained from a multivariate linear model (with ejection fraction and left ventricle outflow tract-aorta angle as covariates) to the mean of the variables. RESULTS: Ten patients treated with aortic valve neocuspidalization were enrolled and compared with 10 AVR patients. The aortic valve neocuspidalization group showed a significantly lower WSS in the outer curvature segments of the proximal and distal ascending aorta as compared to AVR patients (P = 0.0179 and 0.0412, respectively). WSS levels remained significantly lower along the outer curvature of the proximal aorta in the aortic valve neocuspidalization population, even after adjusting the WSS for the ejection fraction and the left ventricle outflow tract-aorta angle [2.44 Pa (2.17-3.01) vs 1.94 Pa (1.72-2.01), P = 0.02]. CONCLUSIONS: Aortic valve neocuspidalization hemodynamical features are potentially associated with a lower WSS in the ascending aorta as compared to commercially available bioprosthetic valves.

Published
2023

5. Quantification of extracellular volume with cardiac computed tomography in patients with left ventricle dysfunction

Author

Baggiano, A, primary, Fusini, L, additional, Mushtaq, S, additional, Annoni, A, additional, Formenti, A, additional, Mancini, E, additional, Fazzari, F, additional, Volpe, A, additional, Tassetti, L, additional, Maragna, R, additional, Junod, D, additional, Gaudenzi, M, additional, Conte, E, additional, Guaricci, A I, additional, and Pontone, G, additional

Published
2023
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6. Plasma exosomes reflect myocardial injury detected by cardiac magnetic resonance in STEMI patients

Author

Baggiano, A, primary, Zara', M, additional, Banfi, C, additional, Campodonico, J, additional, Tedesco, C, additional, Amadio, P, additional, Gili, S, additional, De Dona, G, additional, Sandrini, L, additional, Maragna, R, additional, Junod, D, additional, Fusini, L, additional, Marenzi, G, additional, Pontone, G, additional, and Barbieri, S, additional

Published
2023
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7. Stress computed tomography perfusion versus stress cardiac magnetic resonance for the management of suspected or known coronary artery disease: resources and outcomes impact (STRATEGY II Study)

Author

Baggiano, A, primary, Guglielmo, M, additional, Mushtaq, S, additional, Annoni, A, additional, Formenti, A, additional, Mancini, E, additional, Fusini, L, additional, Tassetti, L, additional, Volpe, A, additional, Marchetti, F, additional, Cilia, F, additional, Fazzari, F, additional, Maragna, R, additional, Junod, D, additional, and Pontone, G, additional

Published
2023
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8. Cardiac magnetic resonance for prophylactic implantable-cardioVerter defibrillator therapy international registry in patients with ischemic cardiomyopathy

Author

Fusini, L, primary, Volpe, A, additional, Baggiano, A, additional, Mushtaq, S, additional, Annoni, A, additional, Mancini, M E, additional, Maragna, R, additional, Fazzari, F, additional, Tassetti, L, additional, Cilia, F, additional, Formenti, A, additional, Marchetti, F, additional, Schwitter, J, additional, Guaricci, A I, additional, and Pontone, G, additional

Published
2023
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9. Quantification Of Extracellular Volume With Cardiac Computed Tomography In Patients With Left Ventricle Dysfunction

Author

Baggiano, A., primary, Maragna, R., additional, Fusini, L., additional, Mushtaq, S., additional, Annoni, A., additional, Formenti, A., additional, Mancini, E., additional, Fazzari, F., additional, Volpe, A., additional, Tassetti, L., additional, Junod, D., additional, Gaudenzi Asinelli, M., additional, Conte, E., additional, Guaricci, A., additional, and Pontone, G., additional

Published
2023
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11. Stress Computed Tomography Perfusion Versus Stress Cardiac Magnetic Resonance For The Management Of Suspectedor Known Coronary Artery Disease: Resources And Outcomes Impact (Strategy II Study)

Author

Baggiano, A., primary, Maragna, R., additional, Guglielmo, M., additional, Mushtaq, S., additional, Annoni, A., additional, Formenti, A., additional, Mancini, E., additional, Fusini, L., additional, Volpe, A., additional, Tassetti, L., additional, Marchetti, F., additional, Cilia, F., additional, Junod, D., additional, Gaudenzi Asinelli, M., additional, Guaricci, A., additional, and Pontone, G., additional

Published
2023
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12. Diagnostic Accuracy Of Dynamic Stress Myocardial Ct Perfusion As Compared With Invasive Coronary Physiology Assessment In Patients With Suspected In-stent Restenosis Or Cad Progression: Results Of Advantage 2 Study

Author

Mushtaq, S., primary, Andreini, D., additional, Conte, E., additional, baggiano, A., additional, trabattoni, D., additional, maragna, R., additional, fazzari, F., additional, collet, C., additional, belmonte, M., additional, LoRusso, G., additional, Bartorelli, A., additional, annoni, A., additional, and pontone, G., additional

Published
2023
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14. Diagnostic performance of deep learning algorithm for analysis of computed tomography myocardial perfusion

Author

Muscogiuri, G, Chiesa, M, Baggiano, A, Spadafora, P, De Santis, R, Guglielmo, M, Scafuri, S, Fusini, L, Mushtaq, S, Conte, E, Annoni, A, Formenti, A, Mancini, M, Ricci, F, Ariano, F, Spiritigliozzi, L, Babbaro, M, Mollace, R, Maragna, R, Giacari, C, Andreini, D, Guaricci, A, Colombo, G, Rabbat, M, Pepi, M, Sardanelli, F, Pontone, G, Muscogiuri G, Chiesa M, Baggiano A, Spadafora P, De Santis R, Guglielmo M, Scafuri S, Fusini L, Mushtaq S, Conte E, Annoni A, Formenti A, Mancini ME, Ricci F, Ariano FP, Spiritigliozzi L, Babbaro M, Mollace R, Maragna R, Giacari CM, Andreini D, Guaricci AI, Colombo GI, Rabbat MG, Pepi M, Sardanelli F, Pontone G., Muscogiuri, G, Chiesa, M, Baggiano, A, Spadafora, P, De Santis, R, Guglielmo, M, Scafuri, S, Fusini, L, Mushtaq, S, Conte, E, Annoni, A, Formenti, A, Mancini, M, Ricci, F, Ariano, F, Spiritigliozzi, L, Babbaro, M, Mollace, R, Maragna, R, Giacari, C, Andreini, D, Guaricci, A, Colombo, G, Rabbat, M, Pepi, M, Sardanelli, F, Pontone, G, Muscogiuri G, Chiesa M, Baggiano A, Spadafora P, De Santis R, Guglielmo M, Scafuri S, Fusini L, Mushtaq S, Conte E, Annoni A, Formenti A, Mancini ME, Ricci F, Ariano FP, Spiritigliozzi L, Babbaro M, Mollace R, Maragna R, Giacari CM, Andreini D, Guaricci AI, Colombo GI, Rabbat MG, Pepi M, Sardanelli F, and Pontone G.

Abstract

Purpose: To evaluate the diagnostic accuracy of a deep learning (DL) algorithm predicting hemodynamically significant coronary artery disease (CAD) by using a rest dataset of myocardial computed tomography perfusion (CTP) as compared to invasive evaluation. Methods: One hundred and twelve consecutive symptomatic patients scheduled for clinically indicated invasive coronary angiography (ICA) underwent CCTA plus static stress CTP and ICA with invasive fractional flow reserve (FFR) for stenoses ranging between 30 and 80%. Subsequently, a DL algorithm for the prediction of significant CAD by using the rest dataset (CTP-DLrest) and stress dataset (CTP-DLstress) was developed. The diagnostic accuracy for identification of significant CAD using CCTA, CCTA + CTP stress, CCTA + CTP-DLrest, and CCTA + CTP-DLstress was measured and compared. The time of analysis for CTP stress, CTP-DLrest, and CTP-DLStress was recorded. Results: Patient-specific sensitivity, specificity, NPV, PPV, accuracy, and area under the curve (AUC) of CCTA alone and CCTA + CTPStress were 100%, 33%, 100%, 54%, 63%, 67% and 86%, 89%, 89%, 86%, 88%, 87%, respectively. Patient-specific sensitivity, specificity, NPV, PPV, accuracy, and AUC of CCTA + DLrest and CCTA + DLstress were 100%, 72%, 100%, 74%, 84%, 96% and 93%, 83%, 94%, 81%, 88%, 98%, respectively. All CCTA + CTP stress, CCTA + CTP-DLRest, and CCTA + CTP-DLStress significantly improved detection of hemodynamically significant CAD compared to CCTA alone (p < 0.01). Time of CTP-DL was significantly lower as compared to human analysis (39.2 ± 3.2 vs. 379.6 ± 68.0 s, p < 0.001). Conclusion: Evaluation of myocardial ischemia using a DL approach on rest CTP datasets is feasible and accurate. This approach may be a useful gatekeeper prior to CTP stress..

Published
2022

15. P72 A CASE OF DRAMATIC HEART CHAMBERS REVERSE REMODELING AND DISEASE REGRESSION IN A PATIENT WITH HEART FAILURE AND END–STAGE RENAL FAILURE TREATED WITH SACUBITRIL/VALSARTAN AND SGLT2I: THE IMPORTANCE OF PUSHING THE BOUNDARIES

Author

Mapelli, M, primary, Mantegazza, V, additional, Ferrari, C, additional, Cimino, R, additional, Maragna, R, additional, Pontone, G, additional, Palermo, P, additional, Amelotti, N, additional, Matteo, S, additional, Pepi, M, additional, and Agostoni, P, additional

Published
2023
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16. Value of 3D echocardiography in the diagnosis of arrhythmogenic right ventricular cardiomyopathy

Author

Addetia, K, Mazzanti, A, Maragna, R, Monti, L, Yamat, M, Kukavica, D, Pagan, E, Kishiki, K, Prado, A, Marino, M, Bagnardi, V, Priori, S, Lang, R, Addetia, Karima, Mazzanti, Andrea, Maragna, Riccardo, Monti, Lorenzo, Yamat, Megan, Kukavica, Deni, Pagan, Eleonora, Kishiki, Kanako, Prado, Aldo, Marino, Maira, Bagnardi, Vincenzo, Priori, Silvia, Lang, Roberto M, Addetia, K, Mazzanti, A, Maragna, R, Monti, L, Yamat, M, Kukavica, D, Pagan, E, Kishiki, K, Prado, A, Marino, M, Bagnardi, V, Priori, S, Lang, R, Addetia, Karima, Mazzanti, Andrea, Maragna, Riccardo, Monti, Lorenzo, Yamat, Megan, Kukavica, Deni, Pagan, Eleonora, Kishiki, Kanako, Prado, Aldo, Marino, Maira, Bagnardi, Vincenzo, Priori, Silvia, and Lang, Roberto M

Abstract

AIMS: The 2010 Task Force Criteria (TFC) require that both right ventricular (RV) regional wall-motion abnormalities (WMA) and specific RV size cut-offs be met in order to fulfil one of the major criterion for arrhythmogenic right ventricular cardiomyopathy (ARVC) diagnosis. Currently, 2D echocardiography (2DE) and cardiovascular magnetic resonance imaging (cMRI) are used to determine if these criteria are met. Little is known about the diagnostic value of 3D echocardiography (3DE) in ARVC. The aim of this study was to determine whether a combination of 2DE-3DE is non-inferior to the currently used 2DE-cMRI combination in the diagnosis of patients with ARVC. METHODS AND RESULTS: Thirty-nine individuals (47±15 years) with suspected ARVC underwent evaluation of the RV with cMRI, 2DE, and 3DE. 3DE and cMRI were independently used to obtain RV volumes, ejection fraction (EF) and determine the presence of segmental RV WMA. Studies were blindly classified as meeting criteria for ARVC in accordance with the 2010 TFC. Kappa statistics were used to test the concordance between 2DE-cMRI and 2DE-3DE approaches. Using the 2DE-cMRI approach, 3/39 were not affected, 5/39 possible, 8/39 borderline, and 23/39 definite ARVC. The proposed 2DE-3DE approach yielded 5/39 not affected, 7/39 possible, 8/39 borderline, and 19/39 definite diagnoses. The two approaches were highly concordant (k = 0.71; 95% confidence interval: 0.44-0.84). Although 3DE underestimated RV volumes in comparison with cMRI, interfering, in some instances with the fulfilment of a major criterion, it was able to identify more RV WMA (28/39) than 2DE (11/39), with a detection-rate comparable to cMRI (33/39) highlighting a unique advantage. CONCLUSION: The combination of 2DE-3DE for ARVC diagnosis is comparable to the conventional 2DE-cMRI approach. 3DE should be performed in all suspected ARVC patients to aide in the detection of WMA.

Published
2023

17. Is EuroSCORE II still a reliable predictor for cardiac surgery mortality in 2022? A retrospective study study

Author

Mastroiacovo, G, Bonomi, A, Ludergnani, M, Franchi, M, Maragna, R, Pirola, S, Baggiano, A, Caglio, A, Pontone, G, Polvani, G, Merlino, L, Mastroiacovo, G, Bonomi, A, Ludergnani, M, Franchi, M, Maragna, R, Pirola, S, Baggiano, A, Caglio, A, Pontone, G, Polvani, G, and Merlino, L

Abstract

OBJECTIVES: The European System for Cardiac Operation Risk Evaluation II (EuroSCORE II) is the most common tool used to evaluate the perioperative risk of mortality after cardiac surgery in Europe, and its use is currently recommended by the relevant guidelines. However, recently, its role has been questioned: Several papers have suggested that these algorithms may no longer be adequate for risk prediction due to an overestimation of adult cardiac surgical risk. Our goal was to validate the EuroSCORE II in the prediction of 30-day in-hospital mortality in patients undergoing open cardiac surgery in a high-volume hospital. METHODS: In this retrospective cohort study, we included all patients who underwent cardiac surgery from January 2016 to May 2022 within the departments of cardiac surgery of the Monzino Cardiology Centre in Milan, Italy. We evaluated the discrimination power of the EuroSCORE II by using the receiver operating characteristic curve and the corresponding area under the curve. We performed calibration plots to assess the concordance between the model's prediction and the observed outcomes. RESULTS: A total of 4, 034 patients were included (mean age = 65.1 years; 68% males), of which 674 (16.7%) underwent isolated coronary artery bypass grafting. The EuroSCORE II showed a good discrimination power in predicting 30-day in-hospital mortality (area under the curve = 0.834). However, for interventions performed in an elective setting, very low values of the EuroSCORE II overestimated the observed mortality, whereas for interventions performed in an emergency setting, EuroSCORE II values above 10 extensively underestimated the observed mortality. CONCLUSIONS: Our study suggests that the EuroSCORE II seems not to be a reliable score in estimating the true risk of death, especially in high-risk patients.

Published
2023

18. The Potential Role of Cardiac CT in the Evaluation of Patients With Known or Suspected Cardiomyopathy: From Traditional Indications to Novel Clinical Applications

Author

Conte, E, Mushtaq, S, Muscogiuri, G, Formenti, A, Annoni, A, Mancini, E, Ricci, F, Melotti, E, Gigante, C, Lorenza, Z, Guglielmo, M, Baggiano, A, Maragna, R, Giacari, C, Carbucicchio, C, Catto, V, Pepi, M, Andreini, D, Pontone, G, Conte E., Mushtaq S., Muscogiuri G., Formenti A., Annoni A., Mancini E., Ricci F., Melotti E., Gigante C., Lorenza Z., Guglielmo M., Baggiano A., Maragna R., Giacari C. M., Carbucicchio C., Catto V., Pepi M., Andreini D., Pontone G., Conte, E, Mushtaq, S, Muscogiuri, G, Formenti, A, Annoni, A, Mancini, E, Ricci, F, Melotti, E, Gigante, C, Lorenza, Z, Guglielmo, M, Baggiano, A, Maragna, R, Giacari, C, Carbucicchio, C, Catto, V, Pepi, M, Andreini, D, Pontone, G, Conte E., Mushtaq S., Muscogiuri G., Formenti A., Annoni A., Mancini E., Ricci F., Melotti E., Gigante C., Lorenza Z., Guglielmo M., Baggiano A., Maragna R., Giacari C. M., Carbucicchio C., Catto V., Pepi M., Andreini D., and Pontone G.

Abstract

After 15 years from its advent in the clinical field, coronary computed tomography (CCTA) is now widely considered as the best first-step test in patients with low-to-moderate pre-test probability of coronary artery disease. Technological innovation was of pivotal importance for the extensive clinical and scientific interest in CCTA. Recently, the advent of last generation wide-coverage CT scans paved the way for new clinical applications of this technique beyond coronary arteries anatomy evaluation. More precisely, both biventricular volume and systolic function quantification and myocardial fibrosis identification appeared to be feasible with last generation CT. In the present review we would focus on potential applications of cardiac computed tomography (CCT), beyond CCTA, for a comprehensive assessment patients with newly diagnosed cardiomyopathy, from technical requirements to novel clinical applications.

Published
2021

20. Use of hydroxychloroquine in hospitalised COVID-19 patients is associated with reduced mortality: Findings from the observational multicentre Italian CORIST study

Author

Castelnuovo, A, Costanzo, S, Antinori, A, Berselli, N, Blandi, L, Bruno, R, Cauda, R, Guaraldi, G, Menicanti, L, My, I, Parruti, G, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Spinoni, E, Stefanini, G, Vergori, A, Ageno, W, Agodi, A, Aiello, L, Agostoni, P, Moghazi, S, Astuto, M, Aucella, F, Barbieri, G, Bartoloni, A, Bonaccio, M, Bonfanti, P, Cacciatore, F, Caiano, L, Cannata, F, Carrozzi, L, Cascio, A, Ciccullo, A, Cingolani, A, Cipollone, F, Colomba, C, Crosta, F, Pra, C, Danzi, G, D'Ardes, D, Donati, K, Giacomo, P, Gennaro, F, Tano, G, D'Offizi, G, Filippini, T, Fusco, F, Gentile, I, Gialluisi, A, Gini, G, Grandone, E, Grisafi, L, Guarnieri, G, Lamonica, S, Landi, F, Leone, A, Maccagni, G, Maccarella, S, Madaro, A, Mapelli, M, Maragna, R, Marra, L, Maresca, G, Marotta, C, Mastroianni, F, Mazzitelli, M, Mengozzi, A, Menichetti, F, Meschiari, M, Minutolo, F, Montineri, A, Mussinelli, R, Mussini, C, Musso, M, Odone, A, Olivieri, M, Pasi, E, Petri, F, Pinchera, B, Pivato, C, Poletti, V, Ravaglia, C, Rinaldi, M, Rognoni, A, Rossato, M, Rossi, I, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Scorzolini, L, Sgariglia, R, Simeone, P, Spinicci, M, Trecarichi, E, Venezia, A, Veronesi, G, Vettor, R, Vianello, A, Vinceti, M, Vocciante, L, De Caterina, R, Iacoviello, L, Castelnuovo A. D., Costanzo S., Antinori A., Berselli N., Blandi L., Bruno R., Cauda R., Guaraldi G., Menicanti L., My I., Parruti G., Patti G., Perlini S., Santilli F., Signorelli C., Spinoni E., Stefanini G. G., Vergori A., Ageno W., Agodi A., Aiello L., Agostoni P., Moghazi S. A., Astuto M., Aucella F., Barbieri G., Bartoloni A., Bonaccio M., Bonfanti P., Cacciatore F., Caiano L., Cannata F., Carrozzi L., Cascio A., Ciccullo A., Cingolani A., Cipollone F., Colomba C., Crosta F., Pra C. D., Danzi G. B., D'Ardes D., Donati K. D. G., Giacomo P. D., Gennaro F. D., Tano G. D., D'Offizi G., Filippini T., Fusco F. M., Gentile I., Gialluisi A., Gini G., Grandone E., Grisafi L., Guarnieri G., Lamonica S., Landi F., Leone A., Maccagni G., Maccarella S., Madaro A., Mapelli M., Maragna R., Marra L., Maresca G., Marotta C., Mastroianni F., Mazzitelli M., Mengozzi A., Menichetti F., Meschiari M., Minutolo F., Montineri A., Mussinelli R., Mussini C., Musso M., Odone A., Olivieri M., Pasi E., Petri F., Pinchera B., Pivato C. A., Poletti V., Ravaglia C., Rinaldi M., Rognoni A., Rossato M., Rossi I., Rossi M., Sabena A., Salinaro F., Sangiovanni V., Sanrocco C., Scorzolini L., Sgariglia R., Simeone P. G., Spinicci M., Trecarichi E. M., Venezia A., Veronesi G., Vettor R., Vianello A., Vinceti M., Vocciante L., De Caterina R., Iacoviello L., Castelnuovo, A, Costanzo, S, Antinori, A, Berselli, N, Blandi, L, Bruno, R, Cauda, R, Guaraldi, G, Menicanti, L, My, I, Parruti, G, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Spinoni, E, Stefanini, G, Vergori, A, Ageno, W, Agodi, A, Aiello, L, Agostoni, P, Moghazi, S, Astuto, M, Aucella, F, Barbieri, G, Bartoloni, A, Bonaccio, M, Bonfanti, P, Cacciatore, F, Caiano, L, Cannata, F, Carrozzi, L, Cascio, A, Ciccullo, A, Cingolani, A, Cipollone, F, Colomba, C, Crosta, F, Pra, C, Danzi, G, D'Ardes, D, Donati, K, Giacomo, P, Gennaro, F, Tano, G, D'Offizi, G, Filippini, T, Fusco, F, Gentile, I, Gialluisi, A, Gini, G, Grandone, E, Grisafi, L, Guarnieri, G, Lamonica, S, Landi, F, Leone, A, Maccagni, G, Maccarella, S, Madaro, A, Mapelli, M, Maragna, R, Marra, L, Maresca, G, Marotta, C, Mastroianni, F, Mazzitelli, M, Mengozzi, A, Menichetti, F, Meschiari, M, Minutolo, F, Montineri, A, Mussinelli, R, Mussini, C, Musso, M, Odone, A, Olivieri, M, Pasi, E, Petri, F, Pinchera, B, Pivato, C, Poletti, V, Ravaglia, C, Rinaldi, M, Rognoni, A, Rossato, M, Rossi, I, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Scorzolini, L, Sgariglia, R, Simeone, P, Spinicci, M, Trecarichi, E, Venezia, A, Veronesi, G, Vettor, R, Vianello, A, Vinceti, M, Vocciante, L, De Caterina, R, Iacoviello, L, Castelnuovo A. D., Costanzo S., Antinori A., Berselli N., Blandi L., Bruno R., Cauda R., Guaraldi G., Menicanti L., My I., Parruti G., Patti G., Perlini S., Santilli F., Signorelli C., Spinoni E., Stefanini G. G., Vergori A., Ageno W., Agodi A., Aiello L., Agostoni P., Moghazi S. A., Astuto M., Aucella F., Barbieri G., Bartoloni A., Bonaccio M., Bonfanti P., Cacciatore F., Caiano L., Cannata F., Carrozzi L., Cascio A., Ciccullo A., Cingolani A., Cipollone F., Colomba C., Crosta F., Pra C. D., Danzi G. B., D'Ardes D., Donati K. D. G., Giacomo P. D., Gennaro F. D., Tano G. D., D'Offizi G., Filippini T., Fusco F. M., Gentile I., Gialluisi A., Gini G., Grandone E., Grisafi L., Guarnieri G., Lamonica S., Landi F., Leone A., Maccagni G., Maccarella S., Madaro A., Mapelli M., Maragna R., Marra L., Maresca G., Marotta C., Mastroianni F., Mazzitelli M., Mengozzi A., Menichetti F., Meschiari M., Minutolo F., Montineri A., Mussinelli R., Mussini C., Musso M., Odone A., Olivieri M., Pasi E., Petri F., Pinchera B., Pivato C. A., Poletti V., Ravaglia C., Rinaldi M., Rognoni A., Rossato M., Rossi I., Rossi M., Sabena A., Salinaro F., Sangiovanni V., Sanrocco C., Scorzolini L., Sgariglia R., Simeone P. G., Spinicci M., Trecarichi E. M., Venezia A., Veronesi G., Vettor R., Vianello A., Vinceti M., Vocciante L., De Caterina R., and Iacoviello L.

Abstract

Background: Hydroxychloroquine (HCQ) was proposed as potential treatment for COVID-19. Objective: We set-up a multicenter Italian collaboration to investigate the relationship between HCQ therapy and COVID-19 in-hospital mortality. Methods: In a retrospective observational study, 3,451 unselected patients hospitalized in 33 clinical centers in Italy, from February 19, 2020 to May 23, 2020, with laboratory-confirmed SARS-CoV-2 infection, were analyzed. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received HCQ with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores, with the addition of subgroup analyses. Results: Out of 3,451 COVID-19 patients, 76.3% received HCQ. Death rates (per 1,000 person-days) for patients receiving or not HCQ were 8.9 and 15.7, respectively. After adjustment for propensity scores, we found 30% lower risk of death in patients receiving HCQ (HR=0.70; 95%CI: 0.59 to 0.84; E-value=1.67). Secondary analyses yielded similar results. The inverse association of HCQ with inpatient mortality was particularly evident in patients having elevated C-reactive protein at entry. Conclusions: HCQ use was associated with a 30% lower risk of death in COVID-19 hospitalized patients. Within the limits of an observational study and awaiting results from randomized controlled trials, these data do not discourage the use of HCQ in inpatients with COVID-19.

Published
2020

21. Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering

Author

Di Castelnuovo, A, Gialluisi, A, Antinori, A, Berselli, N, Blandi, L, Bonaccio, M, Bruno, R, Cauda, R, Costanzo, S, Guaraldi, G, Menicanti, L, Mennuni, M, My, I, Parruti, G, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Stefanini, G, Vergori, A, Ageno, W, Agodi, A, Agostoni, P, Aiello, L, Al Moghazi, S, Arboretti, R, Aucella, F, Barbieri, G, Barchitta, M, Bonfanti, P, Cacciatore, F, Caiano, L, Cannata, F, Carrozzi, L, Cascio, A, Castiglione, G, Cicullo, A, Cingolani, A, Cipollone, F, Colomba, C, Colombo, C, Crisetti, A, Crosta, F, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Tano, G, D'Offizi, G, Fusco, F, Gaudiosi, C, Gentile, I, Gianfagna1, F, Giuliano, G, Graziani, E, Guarnieri, G, Langella, V, Larizza, G, Leone, A, Maccagni, G, Magni, F, Maitan, S, Mancarella, S, Manuele, R, Mapelli, M, Maragna, R, Marcucci, R, Maresca, G, Marongiu, S, Marotta, C, Marra, L, Mastroianni, F, Mengozzi, A, Meschiari, M, Milic, J, Minutolo, F, Mussinelli, R, Mussini, C, Musso, M, Odone, A, Olivieri, M, Palimodde, A, Pasi, E, Pesavento, R, Petri, F, Pivato, C, Poletti, V, Ravaglia, C, Righetti, G, Rognoni, A, Rossato, M, Rossi, I, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Schiano Moriello, N, Scorzolini, L, Sgariglia, R, Simeone, P, Spinicci, M, Tamburrini, E, Torti, C, Trecarichi, E, Vettor, R, Vianello, A, Vinceti, M, Virdis, A, De Caterina, R, Iacoviello, L, Di Castelnuovo, Augusto, Gialluisi, Alessandro, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bonaccio, Marialaura, Bruno, Raffaele, Cauda, Roberto, Costanzo, Simona, Guaraldi, Giovanni, Menicanti, Lorenzo, Mennuni, Marco, My, Ilaria, Parruti, Giustino, Patti, Giuseppe, Perlini, Stefano, Santilli, Francesca, Signorelli, Carlo, Stefanini, Giulio, Vergori, Alessandra, Ageno, Walter, Agodi, Antonella, Agostoni, Piergiuseppe, Aiello, Luca, Al Moghazi, Samir, Arboretti, Rosa, Aucella, Filippo, Barbieri, Greta, Barchitta, Martina, Bonfanti, Paolo, Cacciatore, Francesco, Caiano, Lucia, Cannata, Francesco, Carrozzi, Laura, Cascio, Antonio, Castiglione, Giacomo, Cicullo, Arturo, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Colombo, Crizia, Crisetti, Annalisa, Crosta, Francesca, Danzi, Gian Battista, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Tano, Giuseppe, D'Offizi, Gianpiero, Fusco, Francesco Maria, Gaudiosi, Carlo, Gentile, Ivan, Gianfagna1, Francesco, Giuliano, Gabriele, Graziani, Emauele, Guarnieri, Gabriella, Langella, Valerio, Larizza, Giovanni, Leone, Armando, Maccagni, Gloria, Magni, Federica, Maitan, Stefano, Mancarella, Sandro, Manuele, Rosa, Mapelli, Massimo, Maragna, Riccardo, Marcucci, Rossella, Maresca, Giulio, Marongiu, Silvia, Marotta, Claudia, Marra, Lorenzo, Mastroianni, Franco, Mengozzi, Alessandro, Meschiari, Marianna, Milic, Jovana, Minutolo, Filippo, Mussinelli, Roberta, Mussini, Cristina, Musso, Maria, Odone, Anna, Olivieri, Marco, Palimodde, Antonella, Pasi, Emanuela, Pesavento, Raffaele, Petri, Francesco, Pivato, Carlo A, Poletti, Venerino, Ravaglia, Claudia, Righetti, Giulia, Rognoni, Andrea, Rossato, Marco, Rossi, Ilaria, Rossi, Marianna, Sabena, Anna, Salinaro, Francesco, Sangiovanni, Vincenzo, Sanrocco, Carlo, Schiano Moriello, Nicola, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola Giustina, Spinicci, Michele, Tamburrini, Enrica, Torti, Carlo, Trecarichi, Enrico Maria, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, Virdis, Agostino, De Caterina, Raffaele, Iacoviello, Licia, Di Castelnuovo, A, Gialluisi, A, Antinori, A, Berselli, N, Blandi, L, Bonaccio, M, Bruno, R, Cauda, R, Costanzo, S, Guaraldi, G, Menicanti, L, Mennuni, M, My, I, Parruti, G, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Stefanini, G, Vergori, A, Ageno, W, Agodi, A, Agostoni, P, Aiello, L, Al Moghazi, S, Arboretti, R, Aucella, F, Barbieri, G, Barchitta, M, Bonfanti, P, Cacciatore, F, Caiano, L, Cannata, F, Carrozzi, L, Cascio, A, Castiglione, G, Cicullo, A, Cingolani, A, Cipollone, F, Colomba, C, Colombo, C, Crisetti, A, Crosta, F, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Tano, G, D'Offizi, G, Fusco, F, Gaudiosi, C, Gentile, I, Gianfagna1, F, Giuliano, G, Graziani, E, Guarnieri, G, Langella, V, Larizza, G, Leone, A, Maccagni, G, Magni, F, Maitan, S, Mancarella, S, Manuele, R, Mapelli, M, Maragna, R, Marcucci, R, Maresca, G, Marongiu, S, Marotta, C, Marra, L, Mastroianni, F, Mengozzi, A, Meschiari, M, Milic, J, Minutolo, F, Mussinelli, R, Mussini, C, Musso, M, Odone, A, Olivieri, M, Palimodde, A, Pasi, E, Pesavento, R, Petri, F, Pivato, C, Poletti, V, Ravaglia, C, Righetti, G, Rognoni, A, Rossato, M, Rossi, I, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Schiano Moriello, N, Scorzolini, L, Sgariglia, R, Simeone, P, Spinicci, M, Tamburrini, E, Torti, C, Trecarichi, E, Vettor, R, Vianello, A, Vinceti, M, Virdis, A, De Caterina, R, Iacoviello, L, Di Castelnuovo, Augusto, Gialluisi, Alessandro, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bonaccio, Marialaura, Bruno, Raffaele, Cauda, Roberto, Costanzo, Simona, Guaraldi, Giovanni, Menicanti, Lorenzo, Mennuni, Marco, My, Ilaria, Parruti, Giustino, Patti, Giuseppe, Perlini, Stefano, Santilli, Francesca, Signorelli, Carlo, Stefanini, Giulio, Vergori, Alessandra, Ageno, Walter, Agodi, Antonella, Agostoni, Piergiuseppe, Aiello, Luca, Al Moghazi, Samir, Arboretti, Rosa, Aucella, Filippo, Barbieri, Greta, Barchitta, Martina, Bonfanti, Paolo, Cacciatore, Francesco, Caiano, Lucia, Cannata, Francesco, Carrozzi, Laura, Cascio, Antonio, Castiglione, Giacomo, Cicullo, Arturo, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Colombo, Crizia, Crisetti, Annalisa, Crosta, Francesca, Danzi, Gian Battista, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Tano, Giuseppe, D'Offizi, Gianpiero, Fusco, Francesco Maria, Gaudiosi, Carlo, Gentile, Ivan, Gianfagna1, Francesco, Giuliano, Gabriele, Graziani, Emauele, Guarnieri, Gabriella, Langella, Valerio, Larizza, Giovanni, Leone, Armando, Maccagni, Gloria, Magni, Federica, Maitan, Stefano, Mancarella, Sandro, Manuele, Rosa, Mapelli, Massimo, Maragna, Riccardo, Marcucci, Rossella, Maresca, Giulio, Marongiu, Silvia, Marotta, Claudia, Marra, Lorenzo, Mastroianni, Franco, Mengozzi, Alessandro, Meschiari, Marianna, Milic, Jovana, Minutolo, Filippo, Mussinelli, Roberta, Mussini, Cristina, Musso, Maria, Odone, Anna, Olivieri, Marco, Palimodde, Antonella, Pasi, Emanuela, Pesavento, Raffaele, Petri, Francesco, Pivato, Carlo A, Poletti, Venerino, Ravaglia, Claudia, Righetti, Giulia, Rognoni, Andrea, Rossato, Marco, Rossi, Ilaria, Rossi, Marianna, Sabena, Anna, Salinaro, Francesco, Sangiovanni, Vincenzo, Sanrocco, Carlo, Schiano Moriello, Nicola, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola Giustina, Spinicci, Michele, Tamburrini, Enrica, Torti, Carlo, Trecarichi, Enrico Maria, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, Virdis, Agostino, De Caterina, Raffaele, and Iacoviello, Licia

Abstract

The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February–May 2020). Patients’ characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR[CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster∗HCQ interaction (). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment.

Published
2021

22. Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study

Author

Di Castelnuovo, A, Costanzo, S, Antinori, A, Berselli, N, Blandi, L, Bonaccio, M, Bruno, R, Cauda, R, Gialluisi, A, Guaraldi, G, Menicanti, L, Mennuni, M, My, I, Parruti, A, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Stefanini, G, Vergori, A, Ageno, W, Aiello, L, Agostoni, P, Al Moghazi, S, Arboretti, R, Aucella, F, Barbieri, G, Barchitta, M, Bartoloni, A, Bologna, C, Bonfanti, P, Caiano, L, Carrozzi, L, Cascio, A, Castiglione, G, Chiarito, M, Ciccullo, A, Cingolani, A, Cipollone, F, Colomba, C, Colombo, C, Crosta, F, Dalena, G, Dal Pra, C, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Tano, G, D'Offizi, G, Filippini, T, Maria Fusco, F, Gaudiosi, C, Gentile, I, Gini, G, Grandone, E, Guarnieri, G, Lamanna, G, Larizza, G, Leone, A, Lio, V, Losito, A, Maccagni, G, Maitan, S, Mancarella, S, Manuele, R, Mapelli, M, Maragna, R, Marra, L, Maresca, G, Marotta, C, Mastroianni, F, Mazzitelli, M, Mengozzi, A, Menichetti, F, Milic, J, Minutolo, F, Molena, B, Mussinelli, R, Mussini, C, Musso, M, Odone, A, Olivieri, M, Pasi, E, Perroni, A, Petri, F, Pinchera, B, Pivato, C, Poletti, V, Ravaglia, C, Rossato, M, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Scorzolini, L, Sgariglia, R, Simeone, P, Spinicci, M, Trecarichi, E, Veronesi, G, Vettor, R, Vianello, A, Vinceti, M, Visconti, E, Vocciante, L, De Caterina, R, Iacoviello, L, Di Castelnuovo, Augusto, Costanzo, Simona, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bonaccio, Marialaura, Bruno, Raffaele, Cauda, Roberto, Gialluisi, Alessandro, Guaraldi, Giovanni, Menicanti, Lorenzo, Mennuni, Marco, My, Ilaria, Parruti, Agostino, Patti, Giuseppe, Perlini, Stefano, Santilli, Francesca, Signorelli, Carlo, Stefanini, Giulio G, Vergori, Alessandra, Ageno, Walter, Aiello, Luca, Agostoni, Piergiuseppe, Al Moghazi, Samir, Arboretti, Rosa, Aucella, Filippo, Barbieri, Greta, Barchitta, Martina, Bartoloni, Alessandro, Bologna, Carolina, Bonfanti, Paolo, Caiano, Lucia, Carrozzi, Laura, Cascio, Antonio, Castiglione, Giacomo, Chiarito, Mauro, Ciccullo, Arturo, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Colombo, Crizia, Crosta, Francesco, Dalena, Giovanni, Dal Pra, Chiara, Danzi, Gian Battista, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Tano, Giuseppe, D'Offizi, Gianpiero, Filippini, Tommaso, Maria Fusco, Francesco, Gaudiosi, Carlo, Gentile, Ivan, Gini, Giancarlo, Grandone, Elvira, Guarnieri, Gabriella, Lamanna, Gennaro L F, Larizza, Giovanni, Leone, Armando, Lio, Veronica, Losito, Angela Raffaella, Maccagni, Gloria, Maitan, Stefano, Mancarella, Sandro, Manuele, Rosa, Mapelli, Massimo, Maragna, Riccardo, Marra, Lorenzo, Maresca, Giulio, Marotta, Claudia, Mastroianni, Franco, Mazzitelli, Maria, Mengozzi, Alessandro, Menichetti, Francesco, Milic, Jovana, Minutolo, Filippo, Molena, Beatrice, Mussini, Cristina, Musso, Maria, Odone, Anna, Olivieri, Marco, Pasi, Emanuela, Perroni, Annalisa, Petri, Francesco, Pinchera, Biagio, Pivato, Carlo A, Poletti, Venerino, Ravaglia, Claudia, Rossato, Marco, Rossi, Marianna, Sabena, Anna, Salinaro, Francesco, Sangiovanni, Vincenzo, Sanrocco, Carlo, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola Giustina, Spinicci, Michele, Trecarichi, Enrico Maria, Veronesi, Giovanni, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, Visconti, Elena, Vocciante, Laura, De Caterina, Raffaele, Iacoviello, Licia, Di Castelnuovo, A, Costanzo, S, Antinori, A, Berselli, N, Blandi, L, Bonaccio, M, Bruno, R, Cauda, R, Gialluisi, A, Guaraldi, G, Menicanti, L, Mennuni, M, My, I, Parruti, A, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Stefanini, G, Vergori, A, Ageno, W, Aiello, L, Agostoni, P, Al Moghazi, S, Arboretti, R, Aucella, F, Barbieri, G, Barchitta, M, Bartoloni, A, Bologna, C, Bonfanti, P, Caiano, L, Carrozzi, L, Cascio, A, Castiglione, G, Chiarito, M, Ciccullo, A, Cingolani, A, Cipollone, F, Colomba, C, Colombo, C, Crosta, F, Dalena, G, Dal Pra, C, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Tano, G, D'Offizi, G, Filippini, T, Maria Fusco, F, Gaudiosi, C, Gentile, I, Gini, G, Grandone, E, Guarnieri, G, Lamanna, G, Larizza, G, Leone, A, Lio, V, Losito, A, Maccagni, G, Maitan, S, Mancarella, S, Manuele, R, Mapelli, M, Maragna, R, Marra, L, Maresca, G, Marotta, C, Mastroianni, F, Mazzitelli, M, Mengozzi, A, Menichetti, F, Milic, J, Minutolo, F, Molena, B, Mussinelli, R, Mussini, C, Musso, M, Odone, A, Olivieri, M, Pasi, E, Perroni, A, Petri, F, Pinchera, B, Pivato, C, Poletti, V, Ravaglia, C, Rossato, M, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Scorzolini, L, Sgariglia, R, Simeone, P, Spinicci, M, Trecarichi, E, Veronesi, G, Vettor, R, Vianello, A, Vinceti, M, Visconti, E, Vocciante, L, De Caterina, R, Iacoviello, L, Di Castelnuovo, Augusto, Costanzo, Simona, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bonaccio, Marialaura, Bruno, Raffaele, Cauda, Roberto, Gialluisi, Alessandro, Guaraldi, Giovanni, Menicanti, Lorenzo, Mennuni, Marco, My, Ilaria, Parruti, Agostino, Patti, Giuseppe, Perlini, Stefano, Santilli, Francesca, Signorelli, Carlo, Stefanini, Giulio G, Vergori, Alessandra, Ageno, Walter, Aiello, Luca, Agostoni, Piergiuseppe, Al Moghazi, Samir, Arboretti, Rosa, Aucella, Filippo, Barbieri, Greta, Barchitta, Martina, Bartoloni, Alessandro, Bologna, Carolina, Bonfanti, Paolo, Caiano, Lucia, Carrozzi, Laura, Cascio, Antonio, Castiglione, Giacomo, Chiarito, Mauro, Ciccullo, Arturo, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Colombo, Crizia, Crosta, Francesco, Dalena, Giovanni, Dal Pra, Chiara, Danzi, Gian Battista, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Tano, Giuseppe, D'Offizi, Gianpiero, Filippini, Tommaso, Maria Fusco, Francesco, Gaudiosi, Carlo, Gentile, Ivan, Gini, Giancarlo, Grandone, Elvira, Guarnieri, Gabriella, Lamanna, Gennaro L F, Larizza, Giovanni, Leone, Armando, Lio, Veronica, Losito, Angela Raffaella, Maccagni, Gloria, Maitan, Stefano, Mancarella, Sandro, Manuele, Rosa, Mapelli, Massimo, Maragna, Riccardo, Marra, Lorenzo, Maresca, Giulio, Marotta, Claudia, Mastroianni, Franco, Mazzitelli, Maria, Mengozzi, Alessandro, Menichetti, Francesco, Milic, Jovana, Minutolo, Filippo, Molena, Beatrice, Mussini, Cristina, Musso, Maria, Odone, Anna, Olivieri, Marco, Pasi, Emanuela, Perroni, Annalisa, Petri, Francesco, Pinchera, Biagio, Pivato, Carlo A, Poletti, Venerino, Ravaglia, Claudia, Rossato, Marco, Rossi, Marianna, Sabena, Anna, Salinaro, Francesco, Sangiovanni, Vincenzo, Sanrocco, Carlo, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola Giustina, Spinicci, Michele, Trecarichi, Enrico Maria, Veronesi, Giovanni, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, Visconti, Elena, Vocciante, Laura, De Caterina, Raffaele, and Iacoviello, Licia

Abstract

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients. Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients. Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores. Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs. Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients.

Published
2021

23. Heparin in COVID-19 Patients Is Associated with Reduced In-Hospital Mortality: the Multicenter Italian CORIST Study

Author

Di Castelnuovo, A, Costanzo, S, Antinori, A, Berselli, N, Blandi, L, Bonaccio, M, Cauda, R, Guaraldi, G, Menicanti, L, Mennuni, M, Parruti, G, Patti, G, Santilli, F, Signorelli, C, Vergori, A, Abete, P, Ageno, W, Agodi, A, Agostoni, P, Aiello, L, Al Moghazi, S, Arboretti, R, Astuto, M, Aucella, F, Barbieri, G, Bartoloni, A, Bonfanti, P, Cacciatore, F, Caiano, L, Carrozzi, L, Cascio, A, Ciccullo, A, Cingolani, A, Cipollone, F, Colomba, C, Colombo, C, Crosta, F, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Tano, G, D'Offizi, G, Fantoni, M, Fusco, F, Gentile, I, Gianfagna, F, Grandone, E, Graziani, E, Grisafi, L, Guarnieri, G, Larizza, G, Leone, A, Maccagni, G, Madaro, F, Maitan, S, Mancarella, S, Mapelli, M, Maragna, R, Marcucci, R, Maresca, G, Marongiu, S, Marotta, C, Marra, L, Mastroianni, F, Mazzitelli, M, Mengozzi, A, Menichetti, F, Meschiari, M, Milic, J, Minutolo, F, Molena, B, Montineri, A, Mussini, C, Musso, M, Niola, D, Odone, A, Olivieri, M, Palimodde, A, Parisi, R, Pasi, E, Pesavento, R, Petri, F, Pinchera, B, Poletti, V, Ravaglia, C, Rognoni, A, Rossato, M, Rossi, M, Sangiovanni, V, Sanrocco, C, Scorzolini, L, Sgariglia, R, Simeone, P, Taddei, E, Torti, C, Vettor, R, Vianello, A, Vinceti, M, Virano, A, Vocciante, L, De Caterina, R, Iacoviello, L, Di Castelnuovo, Augusto, Costanzo, Simona, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bonaccio, Marialaura, Cauda, Roberto, Guaraldi, Giovanni, Menicanti, Lorenzo, Mennuni, Marco, Parruti, Giustino, Patti, Giuseppe, Santilli, Francesca, Signorelli, Carlo, Vergori, Alessandra, Abete, Pasquale, Ageno, Walter, Agodi, Antonella, Agostoni, Piergiuseppe, Aiello, Luca, Al Moghazi, Samir, Arboretti, Rosa, Astuto, Marinella, Aucella, Filippo, Barbieri, Greta, Bartoloni, Alessandro, Bonfanti, Paolo, Cacciatore, Francesco, Caiano, Lucia, Carrozzi, Laura, Cascio, Antonio, Ciccullo, Arturo, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Colombo, Crizia, Crosta, Francesca, Danzi, Gian Battista, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Tano, Giuseppe, D'Offizi, Gianpiero, Fantoni, Massimo, Fusco, Francesco Maria, Gentile, Ivan, Gianfagna, Francesco, Grandone, Elvira, Graziani, Emauele, Grisafi, Leonardo, Guarnieri, Gabriella, Larizza, Giovanni, Leone, Armando, Maccagni, Gloria, Madaro, Ferruccio, Maitan, Stefano, Mancarella, Sandro, Mapelli, Massimo, Maragna, Riccardo, Marcucci, Rossella, Maresca, Giulio, Marongiu, Silvia, Marotta, Claudia, Marra, Lorenzo, Mastroianni, Franco, Mazzitelli, Maria, Mengozzi, Alessandro, Menichetti, Francesco, Meschiari, Marianna, Milic, Jovana, Minutolo, Filippo, Molena, Beatrice, Montineri, Arturo, Mussini, Cristina, Musso, Maria, Niola, Daniela, Odone, Anna, Olivieri, Marco, Palimodde, Antonella, Parisi, Roberta, Pasi, Emanuela, Pesavento, Raffaele, Petri, Francesco, Pinchera, Biagio, Poletti, Venerino, Ravaglia, Claudia, Rognoni, Andrea, Rossato, Marco, Rossi, Marianna, Sangiovanni, Vincenzo, Sanrocco, Carlo, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola Giustina, Taddei, Eleonora, Torti, Carlo, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, Virano, Alexandra, Vocciante, Laura, De Caterina, Raffaele, Iacoviello, Licia, Di Castelnuovo, A, Costanzo, S, Antinori, A, Berselli, N, Blandi, L, Bonaccio, M, Cauda, R, Guaraldi, G, Menicanti, L, Mennuni, M, Parruti, G, Patti, G, Santilli, F, Signorelli, C, Vergori, A, Abete, P, Ageno, W, Agodi, A, Agostoni, P, Aiello, L, Al Moghazi, S, Arboretti, R, Astuto, M, Aucella, F, Barbieri, G, Bartoloni, A, Bonfanti, P, Cacciatore, F, Caiano, L, Carrozzi, L, Cascio, A, Ciccullo, A, Cingolani, A, Cipollone, F, Colomba, C, Colombo, C, Crosta, F, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Tano, G, D'Offizi, G, Fantoni, M, Fusco, F, Gentile, I, Gianfagna, F, Grandone, E, Graziani, E, Grisafi, L, Guarnieri, G, Larizza, G, Leone, A, Maccagni, G, Madaro, F, Maitan, S, Mancarella, S, Mapelli, M, Maragna, R, Marcucci, R, Maresca, G, Marongiu, S, Marotta, C, Marra, L, Mastroianni, F, Mazzitelli, M, Mengozzi, A, Menichetti, F, Meschiari, M, Milic, J, Minutolo, F, Molena, B, Montineri, A, Mussini, C, Musso, M, Niola, D, Odone, A, Olivieri, M, Palimodde, A, Parisi, R, Pasi, E, Pesavento, R, Petri, F, Pinchera, B, Poletti, V, Ravaglia, C, Rognoni, A, Rossato, M, Rossi, M, Sangiovanni, V, Sanrocco, C, Scorzolini, L, Sgariglia, R, Simeone, P, Taddei, E, Torti, C, Vettor, R, Vianello, A, Vinceti, M, Virano, A, Vocciante, L, De Caterina, R, Iacoviello, L, Di Castelnuovo, Augusto, Costanzo, Simona, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bonaccio, Marialaura, Cauda, Roberto, Guaraldi, Giovanni, Menicanti, Lorenzo, Mennuni, Marco, Parruti, Giustino, Patti, Giuseppe, Santilli, Francesca, Signorelli, Carlo, Vergori, Alessandra, Abete, Pasquale, Ageno, Walter, Agodi, Antonella, Agostoni, Piergiuseppe, Aiello, Luca, Al Moghazi, Samir, Arboretti, Rosa, Astuto, Marinella, Aucella, Filippo, Barbieri, Greta, Bartoloni, Alessandro, Bonfanti, Paolo, Cacciatore, Francesco, Caiano, Lucia, Carrozzi, Laura, Cascio, Antonio, Ciccullo, Arturo, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Colombo, Crizia, Crosta, Francesca, Danzi, Gian Battista, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Tano, Giuseppe, D'Offizi, Gianpiero, Fantoni, Massimo, Fusco, Francesco Maria, Gentile, Ivan, Gianfagna, Francesco, Grandone, Elvira, Graziani, Emauele, Grisafi, Leonardo, Guarnieri, Gabriella, Larizza, Giovanni, Leone, Armando, Maccagni, Gloria, Madaro, Ferruccio, Maitan, Stefano, Mancarella, Sandro, Mapelli, Massimo, Maragna, Riccardo, Marcucci, Rossella, Maresca, Giulio, Marongiu, Silvia, Marotta, Claudia, Marra, Lorenzo, Mastroianni, Franco, Mazzitelli, Maria, Mengozzi, Alessandro, Menichetti, Francesco, Meschiari, Marianna, Milic, Jovana, Minutolo, Filippo, Molena, Beatrice, Montineri, Arturo, Mussini, Cristina, Musso, Maria, Niola, Daniela, Odone, Anna, Olivieri, Marco, Palimodde, Antonella, Parisi, Roberta, Pasi, Emanuela, Pesavento, Raffaele, Petri, Francesco, Pinchera, Biagio, Poletti, Venerino, Ravaglia, Claudia, Rognoni, Andrea, Rossato, Marco, Rossi, Marianna, Sangiovanni, Vincenzo, Sanrocco, Carlo, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola Giustina, Taddei, Eleonora, Torti, Carlo, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, Virano, Alexandra, Vocciante, Laura, De Caterina, Raffaele, and Iacoviello, Licia

Abstract

INTRODUCTION: A hypercoagulable condition was described in patients with coronavirus disease 2019 (COVID-19) and proposed as a possible pathogenic mechanism contributing to disease progression and lethality.AIM: We evaluated if in-hospital administration of heparin improved survival in a large cohort of Italian COVID-19 patients.METHODS: In a retrospective observational study, 2,574 unselected patients hospitalized in 30 clinical centers in Italy from February 19, 2020 to June 5, 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection were analyzed. The primary endpoint in a time-to event analysis was in-hospital death, comparing patients who received heparin (low-molecular-weight heparin [LMWH] or unfractionated heparin [UFH]) with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores.RESULTS: Out of 2,574 COVID-19 patients, 70.1% received heparin. LMWH was largely the most used formulation (99.5%). Death rates for patients receiving heparin or not were 7.4 and 14.0 per 1,000 person-days, respectively. After adjustment for propensity scores, we found a 40% lower risk of death in patients receiving heparin (hazard ratio=0.60; 95% confidence interval: 0.49-0.74; E-value=2.04). This association was particularly evident in patients with a higher severity of disease or strong coagulation activation.CONCLUSION: In-hospital heparin treatment was associated with a lower mortality, particularly in severely ill COVID-19 patients and in those with strong coagulation activation. The results from randomized clinical trials are eagerly awaited to provide clear-cut recommendations.

Published
2021

24. RAAS inhibitors are not associated with mortality in COVID-19 patients: findings from an observational multicenter study in Italy and a meta-analysis of 19 studies

Author

Di Castelnuovo, A, Costanzo, S, Antinori, A, Berselli, N, Blandi, L, Bonaccio, M, Cauda, R, Gialluisi, A, Guaraldi, G, Menicanti, L, Mennuni, M, Mussinelli, R, My, I, Parruti, G, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Stefanini, G, Vergori, A, Abete, P, Ageno, W, Agostoni, P, Aiello, L, Al Moghazi, S, Arboretti, R, Aucella, F, Barbieri, G, Barchitta, M, Bartoloni, A, Bonfanti, P, Cacciatore, F, Caiano, L, Carrozzi, L, Cascio, A, Castiglione, G, Cianfrone, S, Ciccullo, A, Cingolani, A, Cipollone, F, Colomba, C, Colombo, C, Cozzi, O, Crisetti, A, Crosta, F, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Tano, G, D'Offizi, G, Fusco, F, Gentile, I, Graziani, E, Guarnieri, G, Larizza, G, Leone, A, Lio, V, Lucia, M, Maccagni, G, Madaro, F, Maitan, S, Mancarella, S, Manuele, R, Mapelli, M, Maragna, R, Marcucci, R, Maresca, G, Marongiu, S, Marotta, C, Marra, L, Mastroianni, F, Mazzitelli, M, Mengozzi, A, Menichetti, F, Meschiari, M, Milic, J, Minutolo, F, Molena, B, Mussini, C, Musso, M, Odone, A, Olivieri, M, Palimodde, A, Pasi, E, Pesavento, R, Petri, F, Pinchera, B, Pivato, C, Poletti, V, Ravaglia, C, Rossato, M, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Scoppettuolo, G, Scorzolini, L, Sgariglia, R, Simeone, P, Trecarichi, E, Vettor, R, Vianello, A, Vinceti, M, Virano, A, Vocciante, L, Iacoviello, L, De Caterina, R, Di Castelnuovo, Augusto, Costanzo, Simona, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bonaccio, Marialaura, Cauda, Roberto, Gialluisi, Alessandro, Guaraldi, Giovanni, Menicanti, Lorenzo, Mennuni, Marco, Mussinelli, Roberta, My, Ilaria, Parruti, Giustino, Patti, Giuseppe, Perlini, Stefano, Santilli, Francesca, Signorelli, Carlo, Stefanini, Giulio G, Vergori, Alessandra, Abete, Paolo, Ageno, Walter, Agostoni, Piergiuseppe, Aiello, Luca, Al Moghazi, Samir, Arboretti, Rosa, Aucella, Filippo, Barbieri, Greta, Barchitta, Martina, Bartoloni, Alessandro, Bonfanti, Paolo, Cacciatore, Francesco, Caiano, Lucia, Carrozzi, Laura, Cascio, Antonio, Castiglione, Giacomo, Cianfrone, Stefania, Ciccullo, Arturo, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Colombo, Crizia, Cozzi, Ottavia, Crisetti, Annalisa, Crosta, Francesca, Danzi, Gian Battista, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Tano, Giuseppe, D'Offizi, Gianpiero, Fusco, Francesco Maria, Gentile, Ivan, Graziani, Emauele, Guarnieri, Gabriella, Larizza, Giovanni, Leone, Armando, Lio, Veronica, Lucia, Mothanje Barbara, Maccagni, Gloria, Madaro, Ferruccio, Maitan, Stefano, Mancarella, Sandro, Manuele, Rosa, Mapelli, Massimo, Maragna, Riccardo, Marcucci, Rossella, Maresca, Giulio, Marongiu, Silvia, Marotta, Claudia, Marra, Lorenzo, Mastroianni, Franco, Mazzitelli, Maria, Mengozzi, Alessandro, Menichetti, Francesco, Meschiari, Marianna, Milic, Jovana, Minutolo, Filippo, Molena, Beatrice, Mussini, Cristina, Musso, Maria, Odone, Anna, Olivieri, Marco, Palimodde, Antonella, Pasi, Emanuela, Pesavento, Raffaele, Petri, Francesco, Pinchera, Biagio, Pivato, Carlo A, Poletti, Venerino, Ravaglia, Claudia, Rossato, Marco, Rossi, Marianna, Sabena, Anna, Salinaro, Francesco, Sangiovanni, Vincenzo, Sanrocco, Carlo, Scoppettuolo, Giancarlo, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola Giustina, Trecarichi, Enrico Maria, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, Virano, Alexandra, Vocciante, Laura, Iacoviello, Licia, De Caterina, Raffaele, Di Castelnuovo, A, Costanzo, S, Antinori, A, Berselli, N, Blandi, L, Bonaccio, M, Cauda, R, Gialluisi, A, Guaraldi, G, Menicanti, L, Mennuni, M, Mussinelli, R, My, I, Parruti, G, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Stefanini, G, Vergori, A, Abete, P, Ageno, W, Agostoni, P, Aiello, L, Al Moghazi, S, Arboretti, R, Aucella, F, Barbieri, G, Barchitta, M, Bartoloni, A, Bonfanti, P, Cacciatore, F, Caiano, L, Carrozzi, L, Cascio, A, Castiglione, G, Cianfrone, S, Ciccullo, A, Cingolani, A, Cipollone, F, Colomba, C, Colombo, C, Cozzi, O, Crisetti, A, Crosta, F, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Tano, G, D'Offizi, G, Fusco, F, Gentile, I, Graziani, E, Guarnieri, G, Larizza, G, Leone, A, Lio, V, Lucia, M, Maccagni, G, Madaro, F, Maitan, S, Mancarella, S, Manuele, R, Mapelli, M, Maragna, R, Marcucci, R, Maresca, G, Marongiu, S, Marotta, C, Marra, L, Mastroianni, F, Mazzitelli, M, Mengozzi, A, Menichetti, F, Meschiari, M, Milic, J, Minutolo, F, Molena, B, Mussini, C, Musso, M, Odone, A, Olivieri, M, Palimodde, A, Pasi, E, Pesavento, R, Petri, F, Pinchera, B, Pivato, C, Poletti, V, Ravaglia, C, Rossato, M, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Scoppettuolo, G, Scorzolini, L, Sgariglia, R, Simeone, P, Trecarichi, E, Vettor, R, Vianello, A, Vinceti, M, Virano, A, Vocciante, L, Iacoviello, L, De Caterina, R, Di Castelnuovo, Augusto, Costanzo, Simona, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bonaccio, Marialaura, Cauda, Roberto, Gialluisi, Alessandro, Guaraldi, Giovanni, Menicanti, Lorenzo, Mennuni, Marco, Mussinelli, Roberta, My, Ilaria, Parruti, Giustino, Patti, Giuseppe, Perlini, Stefano, Santilli, Francesca, Signorelli, Carlo, Stefanini, Giulio G, Vergori, Alessandra, Abete, Paolo, Ageno, Walter, Agostoni, Piergiuseppe, Aiello, Luca, Al Moghazi, Samir, Arboretti, Rosa, Aucella, Filippo, Barbieri, Greta, Barchitta, Martina, Bartoloni, Alessandro, Bonfanti, Paolo, Cacciatore, Francesco, Caiano, Lucia, Carrozzi, Laura, Cascio, Antonio, Castiglione, Giacomo, Cianfrone, Stefania, Ciccullo, Arturo, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Colombo, Crizia, Cozzi, Ottavia, Crisetti, Annalisa, Crosta, Francesca, Danzi, Gian Battista, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Tano, Giuseppe, D'Offizi, Gianpiero, Fusco, Francesco Maria, Gentile, Ivan, Graziani, Emauele, Guarnieri, Gabriella, Larizza, Giovanni, Leone, Armando, Lio, Veronica, Lucia, Mothanje Barbara, Maccagni, Gloria, Madaro, Ferruccio, Maitan, Stefano, Mancarella, Sandro, Manuele, Rosa, Mapelli, Massimo, Maragna, Riccardo, Marcucci, Rossella, Maresca, Giulio, Marongiu, Silvia, Marotta, Claudia, Marra, Lorenzo, Mastroianni, Franco, Mazzitelli, Maria, Mengozzi, Alessandro, Menichetti, Francesco, Meschiari, Marianna, Milic, Jovana, Minutolo, Filippo, Molena, Beatrice, Mussini, Cristina, Musso, Maria, Odone, Anna, Olivieri, Marco, Palimodde, Antonella, Pasi, Emanuela, Pesavento, Raffaele, Petri, Francesco, Pinchera, Biagio, Pivato, Carlo A, Poletti, Venerino, Ravaglia, Claudia, Rossato, Marco, Rossi, Marianna, Sabena, Anna, Salinaro, Francesco, Sangiovanni, Vincenzo, Sanrocco, Carlo, Scoppettuolo, Giancarlo, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola Giustina, Trecarichi, Enrico Maria, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, Virano, Alexandra, Vocciante, Laura, Iacoviello, Licia, and De Caterina, Raffaele

Abstract

Objective: The hypothesis that been set forward that use of Renin Angiotensin Aldosterone System (RAAS) inhibitors is associated with COVID-19 severity. We set-up a multicenter Italian collaboration (CORIST Project, ClinicalTrials.gov ID: NCT04318418) to retrospectively investigate the relationship between RAAS inhibitors and COVID-19 in-hospital mortality. We also carried out an updated meta-analysis on the relevant studies. Methods: We analyzed 4,069 unselected patients with laboratory-confirmed SARS-CoV-2 infection and hospitalized in 34 clinical centers in Italy from February 19, 2020 to May 23, 2020. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received angiotensin-converting-enzyme inhibitors (ACE-I) or angiotensin-receptor blockers (ARB) with patients who did not. Articles for the meta-analysis were retrieved until July 13th, 2020 by searching in web-based libraries, and data were combined using the general variance-based method. Results: Out of 4,069 COVID-19 patients, 13.5% and 13.3% received ACE-I or ARB, respectively. Use of neither ACE-I nor ARB was associated with mortality (multivariable hazard ratio (HR) adjusted also for COVID-19 treatments: 0.96, 95% confidence interval 0.77-1.20 and HR=0.89, 0.67-1.19 for ACE-I and ARB, respectively). Findings were similar restricting the analysis to hypertensive (N=2,057) patients (HR=1.00, 0.78-1.26 and HR=0.88, 0.65-1.20) or when ACE-I or ARB were considered as a single group. Results from the meta-analysis (19 studies, 29,057 COVID-19 adult patients, 9,700 with hypertension) confirmed the absence of association. Conclusions: In this observational study and meta-analysis of the literature, ACE-I or ARB use was not associated with severity or in-hospital mortality in COVID-19 patients.

Published
2020

25. Common cardiovascular risk factors and in-hospital mortality in 3,894 patients with COVID-19: survival analysis and machine learning-based findings from the multicentre Italian CORIST Study

Author

Di Castelnuovo, A, Bonaccio, M, Costanzo, S, Gialluisi, A, Antinori, A, Berselli, N, Blandi, L, Bruno, R, Cauda, R, Guaraldi, G, My, I, Menicanti, L, Parruti, A, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Stefanini, G, Vergori, A, Abdeddaim, A, Ageno, W, Agodi, A, Agostoni, P, Aiello, L, Al Moghazi, S, Aucella, F, Barbieri, G, Bartoloni, A, Bologna, C, Bonfanti, P, Brancati, S, Cacciatore, F, Caiano, L, Cannata, F, Carrozzi, L, Cascio, A, Cingolani, A, Cipollone, F, Colomba, C, Crisetti, A, Crosta, F, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Palma, G, Di Tano, G, Fantoni, M, Filippini, T, Fioretto, P, Fusco, F, Gentile, I, Grisafi, L, Guarnieri, G, Landi, F, Larizza, G, Leone, A, Maccagni, G, Maccarella, S, Mapelli, M, Maragna, R, Marcucci, R, Maresca, G, Marotta, C, Marra, L, Mastroianni, F, Mengozzi, A, Menichetti, F, Milic, J, Miurri, R, Montineri, A, Mussinelli, R, Mussini, C, Musso, M, Odone, A, Olivieri, M, Pasi, E, Petri, F, Pinchera, B, Pivato, C, Pizzi, R, Poletti, V, Raffaelli, F, Ravaglia, C, Righetti, G, Rognoni, A, Rossato, M, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Scarafino, A, Scorzolini, L, Sgariglia, R, Simeone, P, Spinoni, E, Torti, C, Trecarichi, E, Vezzani, F, Veronesi, G, Vettor, R, Vianello, A, Vinceti, M, De Caterina, R, Iacoviello, L, Di Castelnuovo, Augusto, Bonaccio, Marialaura, Costanzo, Simona, Gialluisi, Alessandro, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bruno, Raffaele, Cauda, Roberto, Guaraldi, Giovanni, My, Ilaria, Menicanti, Lorenzo, Parruti, Agostino, Patti, Giuseppe, Perlini, Stefano, Santilli, Francesca, Signorelli, Carlo, Stefanini, Giulio G., Vergori, Alessandra, Abdeddaim, Amina, Ageno, Walter, Agodi, Antonella, Agostoni, Piergiuseppe, Aiello, Luca, Al Moghazi, Samir, Aucella, Filippo, Barbieri, Greta, Bartoloni, Alessandro, Bologna, Carolina, Bonfanti, Paolo, Brancati, Serena, Cacciatore, Francesco, Caiano, Lucia, Cannata, Francesco, Carrozzi, Laura, Cascio, Antonio, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Crisetti, Annalisa, Crosta, Francesco, Danzi, Gian Battista, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Palma, Gisella, Di Tano, Giuseppe, Fantoni, Massimo, Filippini, Tommaso, Fioretto, Paola, Fusco, Francesco Maria, Gentile, Ivan, Grisafi, Leonardo, Guarnieri, Gabriella, Landi, Francesco, Larizza, Giovanni, Leone, Armando, Maccagni, Gloria, Maccarella, Sandro, Mapelli, Massimo, Maragna, Riccardo, Marcucci, Rossella, Maresca, Giulio, Marotta, Claudia, Marra, Lorenzo, Mastroianni, Franco, Mengozzi, Alessandro, Menichetti, Francesco, Milic, Jovana, Miurri, Rita, Montineri, Arturo, Mussinelli, Roberta, Mussini, Cristina, Musso, Maria, Odone, Anna, Olivieri, Marco, Pasi, Emanuela, Petri, Francesco, Pinchera, Biagio, Pivato, Carlo A., Pizzi, Roberto, Poletti, Venerino, Raffaelli, Francesca, Ravaglia, Claudia, Righetti, Giulia, Rognoni, Andrea, Rossato, Marco, Rossi, Marianna, Sabena, Anna, Salinaro, Francesco, Sangiovanni, Vincenzo, Sanrocco, Carlo, Scarafino, Antonio, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola Giustina, Spinoni, Enrico, Torti, Carlo, Trecarichi, Enrico Maria, Vezzani, Francesca, Veronesi, Giovanni, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, De Caterina, Raffaele, Iacoviello, Licia, Di Castelnuovo, A, Bonaccio, M, Costanzo, S, Gialluisi, A, Antinori, A, Berselli, N, Blandi, L, Bruno, R, Cauda, R, Guaraldi, G, My, I, Menicanti, L, Parruti, A, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Stefanini, G, Vergori, A, Abdeddaim, A, Ageno, W, Agodi, A, Agostoni, P, Aiello, L, Al Moghazi, S, Aucella, F, Barbieri, G, Bartoloni, A, Bologna, C, Bonfanti, P, Brancati, S, Cacciatore, F, Caiano, L, Cannata, F, Carrozzi, L, Cascio, A, Cingolani, A, Cipollone, F, Colomba, C, Crisetti, A, Crosta, F, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Palma, G, Di Tano, G, Fantoni, M, Filippini, T, Fioretto, P, Fusco, F, Gentile, I, Grisafi, L, Guarnieri, G, Landi, F, Larizza, G, Leone, A, Maccagni, G, Maccarella, S, Mapelli, M, Maragna, R, Marcucci, R, Maresca, G, Marotta, C, Marra, L, Mastroianni, F, Mengozzi, A, Menichetti, F, Milic, J, Miurri, R, Montineri, A, Mussinelli, R, Mussini, C, Musso, M, Odone, A, Olivieri, M, Pasi, E, Petri, F, Pinchera, B, Pivato, C, Pizzi, R, Poletti, V, Raffaelli, F, Ravaglia, C, Righetti, G, Rognoni, A, Rossato, M, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Scarafino, A, Scorzolini, L, Sgariglia, R, Simeone, P, Spinoni, E, Torti, C, Trecarichi, E, Vezzani, F, Veronesi, G, Vettor, R, Vianello, A, Vinceti, M, De Caterina, R, Iacoviello, L, Di Castelnuovo, Augusto, Bonaccio, Marialaura, Costanzo, Simona, Gialluisi, Alessandro, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bruno, Raffaele, Cauda, Roberto, Guaraldi, Giovanni, My, Ilaria, Menicanti, Lorenzo, Parruti, Agostino, Patti, Giuseppe, Perlini, Stefano, Santilli, Francesca, Signorelli, Carlo, Stefanini, Giulio G., Vergori, Alessandra, Abdeddaim, Amina, Ageno, Walter, Agodi, Antonella, Agostoni, Piergiuseppe, Aiello, Luca, Al Moghazi, Samir, Aucella, Filippo, Barbieri, Greta, Bartoloni, Alessandro, Bologna, Carolina, Bonfanti, Paolo, Brancati, Serena, Cacciatore, Francesco, Caiano, Lucia, Cannata, Francesco, Carrozzi, Laura, Cascio, Antonio, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Crisetti, Annalisa, Crosta, Francesco, Danzi, Gian Battista, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Palma, Gisella, Di Tano, Giuseppe, Fantoni, Massimo, Filippini, Tommaso, Fioretto, Paola, Fusco, Francesco Maria, Gentile, Ivan, Grisafi, Leonardo, Guarnieri, Gabriella, Landi, Francesco, Larizza, Giovanni, Leone, Armando, Maccagni, Gloria, Maccarella, Sandro, Mapelli, Massimo, Maragna, Riccardo, Marcucci, Rossella, Maresca, Giulio, Marotta, Claudia, Marra, Lorenzo, Mastroianni, Franco, Mengozzi, Alessandro, Menichetti, Francesco, Milic, Jovana, Miurri, Rita, Montineri, Arturo, Mussinelli, Roberta, Mussini, Cristina, Musso, Maria, Odone, Anna, Olivieri, Marco, Pasi, Emanuela, Petri, Francesco, Pinchera, Biagio, Pivato, Carlo A., Pizzi, Roberto, Poletti, Venerino, Raffaelli, Francesca, Ravaglia, Claudia, Righetti, Giulia, Rognoni, Andrea, Rossato, Marco, Rossi, Marianna, Sabena, Anna, Salinaro, Francesco, Sangiovanni, Vincenzo, Sanrocco, Carlo, Scarafino, Antonio, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola Giustina, Spinoni, Enrico, Torti, Carlo, Trecarichi, Enrico Maria, Vezzani, Francesca, Veronesi, Giovanni, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, De Caterina, Raffaele, and Iacoviello, Licia

Abstract

Background and aims: There is poor knowledge on characteristics, comorbidities and laboratory measures associated with risk for adverse outcomes and in-hospital mortality in European Countries. We aimed at identifying baseline characteristics predisposing COVID-19 patients to in-hospital death. Methods and results: Retrospective observational study on 3894 patients with SARS-CoV-2 infection hospitalized from February 19th to May 23rd, 2020 and recruited in 30 clinical centres distributed throughout Italy. Machine learning (random forest)-based and Cox survival analysis. 61.7% of participants were men (median age 67 years), followed up for a median of 13 days. In-hospital mortality exhibited a geographical gradient, Northern Italian regions featuring more than twofold higher death rates as compared to Central/Southern areas (15.6% vs 6.4%, respectively). Machine learning analysis revealed that the most important features in death classification were impaired renal function, elevated C reactive protein and advanced age. These findings were confirmed by multivariable Cox survival analysis (hazard ratio (HR): 8.2; 95% confidence interval (CI) 4.6–14.7 for age ≥85 vs 18–44 y); HR = 4.7; 2.9–7.7 for estimated glomerular filtration rate levels <15 vs ≥ 90 mL/min/1.73 m2; HR = 2.3; 1.5–3.6 for C-reactive protein levels ≥10 vs ≤ 3 mg/L). No relation was found with obesity, tobacco use, cardiovascular disease and related-comorbidities. The associations between these variables and mortality were substantially homogenous across all sub-groups analyses. Conclusions: Impaired renal function, elevated C-reactive protein and advanced age were major predictors of in-hospital death in a large cohort of unselected patients with COVID-19, admitted to 30 different clinical centres all over Italy.

Published
2020

26. Common cardiovascular risk factors and in-hospital mortality in 3,894 patients with COVID-19: survival analysis and machine learning-based findings from the multicentre Italian CORIST Study

Author

Di Castelnuovo, A., Bonaccio, M., Costanzo, S., Gialluisi, A., Antinori, A., Berselli, N., Blandi, L., Bruno, Rosa Anna, Cauda, Roberto, Guaraldi, G., My, I., Menicanti, L., Parruti, G., Patti, G., Perlini, S., Santilli, F., Signorelli, C., Stefanini, G. G., Vergori, A., Abdeddaim, A., Ageno, W., Agodi, A., Agostoni, P., Aiello, L., Al Moghazi, S., Aucella, F., Barbieri, G., Bartoloni, A., Bologna, C., Bonfanti, P., Brancati, S., Cacciatore, F., Caiano, L., Cannata, F., Carrozzi, L., Cascio, A., Cingolani, Antonella, Cipollone, F., Colomba, C., Crisetti, A., Crosta, F., Danzi, G. B., D'Ardes, D., De Gaetano Donati, Katleen, Di Gennaro, F., Di Palma, G., Di Tano, G., Fantoni, Massimo, Filippini, T., Fioretto, P., Fusco, F. M., Gentile, I., Grisafi, L., Guarnieri, G., Landi, Francesco, Larizza, G., Leone, A., Maccagni, G., Maccarella, S., Mapelli, M., Maragna, R., Marcucci, R., Maresca, G., Marotta, C., Marra, L., Mastroianni, F., Mengozzi, A., Menichetti, F., Milic, J., Murri, Rita, Montineri, A., Mussinelli, R., Mussini, C., Musso, M., Odone, A., Olivieri, M., Pasi, E., Petri, F., Pinchera, B., Pivato, C. A., Pizzi, R., Poletti, V., Raffaelli, Francesca, Ravaglia, C., Righetti, G., Rognoni, A., Rossato, M., Rossi, M., Sabena, A., Salinaro, F., Sangiovanni, V., Sanrocco, C., Scarafino, A., Scorzolini, L., Sgariglia, R., Simeone, P. G., Spinoni, E., Torti, C., Trecarichi, Enrico Maria, Vezzani, F., Veronesi, G., Vettor, R., Vianello, A., Vinceti, M., De Caterina, R., Iacoviello, L., Bruno R., Cauda R. (ORCID:0000-0002-1498-4229), Cingolani A. (ORCID:0000-0002-3793-2755), de Gaetano Donati K., Fantoni M. (ORCID:0000-0001-6913-8460), Landi F. (ORCID:0000-0002-3472-1389), Murri R. (ORCID:0000-0003-4263-7854), Raffaelli F., Trecarichi E. M., Di Castelnuovo, A., Bonaccio, M., Costanzo, S., Gialluisi, A., Antinori, A., Berselli, N., Blandi, L., Bruno, Rosa Anna, Cauda, Roberto, Guaraldi, G., My, I., Menicanti, L., Parruti, G., Patti, G., Perlini, S., Santilli, F., Signorelli, C., Stefanini, G. G., Vergori, A., Abdeddaim, A., Ageno, W., Agodi, A., Agostoni, P., Aiello, L., Al Moghazi, S., Aucella, F., Barbieri, G., Bartoloni, A., Bologna, C., Bonfanti, P., Brancati, S., Cacciatore, F., Caiano, L., Cannata, F., Carrozzi, L., Cascio, A., Cingolani, Antonella, Cipollone, F., Colomba, C., Crisetti, A., Crosta, F., Danzi, G. B., D'Ardes, D., De Gaetano Donati, Katleen, Di Gennaro, F., Di Palma, G., Di Tano, G., Fantoni, Massimo, Filippini, T., Fioretto, P., Fusco, F. M., Gentile, I., Grisafi, L., Guarnieri, G., Landi, Francesco, Larizza, G., Leone, A., Maccagni, G., Maccarella, S., Mapelli, M., Maragna, R., Marcucci, R., Maresca, G., Marotta, C., Marra, L., Mastroianni, F., Mengozzi, A., Menichetti, F., Milic, J., Murri, Rita, Montineri, A., Mussinelli, R., Mussini, C., Musso, M., Odone, A., Olivieri, M., Pasi, E., Petri, F., Pinchera, B., Pivato, C. A., Pizzi, R., Poletti, V., Raffaelli, Francesca, Ravaglia, C., Righetti, G., Rognoni, A., Rossato, M., Rossi, M., Sabena, A., Salinaro, F., Sangiovanni, V., Sanrocco, C., Scarafino, A., Scorzolini, L., Sgariglia, R., Simeone, P. G., Spinoni, E., Torti, C., Trecarichi, Enrico Maria, Vezzani, F., Veronesi, G., Vettor, R., Vianello, A., Vinceti, M., De Caterina, R., Iacoviello, L., Bruno R., Cauda R. (ORCID:0000-0002-1498-4229), Cingolani A. (ORCID:0000-0002-3793-2755), de Gaetano Donati K., Fantoni M. (ORCID:0000-0001-6913-8460), Landi F. (ORCID:0000-0002-3472-1389), Murri R. (ORCID:0000-0003-4263-7854), Raffaelli F., and Trecarichi E. M.

Abstract

Background and aims: There is poor knowledge on characteristics, comorbidities and laboratory measures associated with risk for adverse outcomes and in-hospital mortality in European Countries. We aimed at identifying baseline characteristics predisposing COVID-19 patients to in-hospital death. Methods and results: Retrospective observational study on 3894 patients with SARS-CoV-2 infection hospitalized from February 19th to May 23rd, 2020 and recruited in 30 clinical centres distributed throughout Italy. Machine learning (random forest)-based and Cox survival analysis. 61.7% of participants were men (median age 67 years), followed up for a median of 13 days. In-hospital mortality exhibited a geographical gradient, Northern Italian regions featuring more than twofold higher death rates as compared to Central/Southern areas (15.6% vs 6.4%, respectively). Machine learning analysis revealed that the most important features in death classification were impaired renal function, elevated C reactive protein and advanced age. These findings were confirmed by multivariable Cox survival analysis (hazard ratio (HR): 8.2; 95% confidence interval (CI) 4.6–14.7 for age ≥85 vs 18–44 y); HR = 4.7; 2.9–7.7 for estimated glomerular filtration rate levels <15 vs ≥ 90 mL/min/1.73 m2; HR = 2.3; 1.5–3.6 for C-reactive protein levels ≥10 vs ≤ 3 mg/L). No relation was found with obesity, tobacco use, cardiovascular disease and related-comorbidities. The associations between these variables and mortality were substantially homogenous across all sub-groups analyses. Conclusions: Impaired renal function, elevated C-reactive protein and advanced age were major predictors of in-hospital death in a large cohort of unselected patients with COVID-19, admitted to 30 different clinical centres all over Italy.

Published
2020

27. Endomyocardial biopsy: what future in arrhythmogenic right ventricular dysplasia diagnosis?

Author

Maragna, R, primary, Trombara, F, additional, Frappampina, A, additional, Dello Russo, A, additional, Gasperetti, A, additional, Catto, V, additional, Conte, E, additional, Vettor, G, additional, Sicuso, R, additional, Sommariva, E, additional, Natale, A, additional, Andreini, D, additional, Basso, C, additional, Tondo, C, additional, and Casella, M, additional

Published
2020
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29. Arrhythmogenic Right Ventricular Cardiomyopathy: Clinical Course and Predictors of Arrhythmic Risk

Author

Mazzanti, A, Ng, K, Faragli, A, Maragna, R, Chiodaroli, E, Orphanou, N, Monteforte, N, Memmi, M, Gambelli, P, Novelli, V, Bloise, R, Catalano, O, Moro, G, Tibollo, V, Morini, M, Bellazzi, R, Napolitano, C, Priori, S., BAGNARDI, VINCENZO, Mazzanti, A, Ng, K, Faragli, A, Maragna, R, Chiodaroli, E, Orphanou, N, Monteforte, N, Memmi, M, Gambelli, P, Novelli, V, Bloise, R, Catalano, O, Moro, G, Tibollo, V, Morini, M, Bellazzi, R, Napolitano, C, Bagnardi, V, and Priori, S

Subjects
implantable cardioverter-defibrillator, athlete, ventricular tachycardia, genetic, sudden cardiac death
Abstract

Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a leading cause of sudden cardiac death, but its progression over time and predictors of arrhythmias are still being defined. Objectives This study sought to describe the clinical course of ARVC and occurrence of life-threatening arrhythmic events (LAE) and cardiovascular mortality; identify risk factors associated with increased LAE risk; and define the response to therapy. Methods We determined the clinical course of 301 consecutive patients with ARVC using the Kaplan-Meier method adjusted to avoid the bias of delayed entry. Predictors of LAE over 5.8 years of follow-up were determined with Cox multivariable analysis. Treatment efficacy was assessed comparing LAE rates during matched time intervals. Results A first LAE occurred in 1.5 per 100 person-years between birth and age 20 years, in 4.0 per 100 person-years between ages 21 and 40 years, and in 2.4 per 100 person-years between ages 41 and 60 years. Cumulative probability of a first LAE at follow-up was 14% at 5 years, 23% at 10 years, and 30% at 15 years. Higher risk of LAE was predicted by atrial fibrillation (hazard ratio [HR]: 4.38; p = 0.002), syncope (HR: 3.36; p < 0.001), participation in strenuous exercise after the diagnosis (HR: 2.98; p = 0.028), hemodynamically tolerated sustained monomorphic ventricular tachycardia (HR: 2.19; p = 0.023), and male sex (HR: 2.49; p = 0.012). No difference was observed in the occurrence of LAE before and after treatment with amiodarone, beta-blockers, sotalol, or ablation. A total of 81 patients received an implantable cardioverter-defibrillator, 34 were successfully defibrillated. Conclusions The high risk of life-threatening arrhythmias in patients with ARVC spans from adolescence to advanced age, reaching its peak between ages 21 and 40 years. Atrial fibrillation, syncope, participation in strenuous exercise after the diagnosis of ARVC, hemodynamically tolerated sustained monomorphic ventricular tachycardia, and male sex predicted lethal arrhythmias at follow-up. The lack of efficacy of antiarrhythmic therapy and the life-saving role of the implantable cardioverter-defibrillator highlight the importance of risk stratification for patient management.

Published
2016

30. Interplay Between Genetic Substrate, QTc Duration, and Arrhythmia Risk in Patients With Long QT Syndrome

Author

Mazzanti, A, Maragna, R, Vacanti, G, Monteforte, N, Bloise, R, Marino, M, Braghieri, L, Gambelli, P, Memmi, M, Pagan, E, Morini, M, Malovini, A, Ortiz, M, Sacilotto, L, Bellazzi, R, Monserrat, L, Napolitano, C, Bagnardi, V, Priori, S, Priori, SG, Mazzanti, A, Maragna, R, Vacanti, G, Monteforte, N, Bloise, R, Marino, M, Braghieri, L, Gambelli, P, Memmi, M, Pagan, E, Morini, M, Malovini, A, Ortiz, M, Sacilotto, L, Bellazzi, R, Monserrat, L, Napolitano, C, Bagnardi, V, Priori, S, and Priori, SG

Abstract

Background: Long QT syndrome (LQTS) is a common inheritable arrhythmogenic disorder, often secondary to mutations in the KCNQ1, KCNH2, and SCN5A genes. The disease is characterized by a prolonged ventricular repolarization (QTc interval) that confers susceptibility to life-threatening arrhythmic events (LAEs). Objectives: This study sought to create an evidence-based risk stratification scheme to personalize the quantification of the arrhythmic risk in patients with LQTS. Methods: Data from 1,710 patients with LQTS followed up for a median of 7.1 years (interquartile range [IQR]: 2.7 to 13.4 years) were analyzed to estimate the 5-year risk of LAEs based on QTc duration and genotype and to assess the antiarrhythmic efficacy of beta-blockers. Results: The relationship between QTc duration and risk of events was investigated by comparison of linear and cubic spline models, and the linear model provided the best fit. The 5-year risk of LAEs while patients were off therapy was then calculated in a multivariable Cox model with QTc and genotype considered as independent factors. The estimated risk of LAEs increased by 15% for every 10-ms increment of QTc duration for all genotypes. Intergenotype comparison showed that the risk for patients with LQT2 and LTQ3 increased by 130% and 157% at any QTc duration versus patients with LQT1. Analysis of response to beta-blockers showed that only nadolol reduced the arrhythmic risk in all genotypes significantly compared with no therapy (hazard ratio: 0.38; 95% confidence interval: 0.15 to 0.93; p = 0.03). Conclusions: The study provides an estimator of risk of LAEs in LQTS that allows a granular estimate of 5-year arrhythmic risk and demonstrate the superiority of nadolol in reducing the risk of LAEs in LQTS

Published
2018

33. Hydroquinidine Prevents Life-Threatening Arrhythmic Events in Patients With Short QT Syndrome

Author

Mazzanti, A, Maragna, R, Vacanti, G, Kostopoulou, A, Marino, M, Monteforte, N, Bloise, R, Underwood, K, Tibollo, V, Pagan, E, Napolitano, C, Bellazzi, R, Bagnardi, V, Priori, S, Priori, SG, Mazzanti, A, Maragna, R, Vacanti, G, Kostopoulou, A, Marino, M, Monteforte, N, Bloise, R, Underwood, K, Tibollo, V, Pagan, E, Napolitano, C, Bellazzi, R, Bagnardi, V, Priori, S, and Priori, SG

Abstract

Background Short QT syndrome (SQTS) is a rare and life-threatening arrhythmogenic syndrome characterized by abbreviated repolarization. Hydroquinidine (HQ) prolongs the QT interval in SQTS patients, although whether it reduces cardiac events is currently unknown. Objectives This study investigated whether long-term treatment with HQ reduces the occurrence of life-threatening arrhythmic events (LAE) (cardiac arrest or sudden cardiac death) in SQTS patients. Methods In this cohort study on consecutive SQTS patients, 2 analyses were performed: 1) a matched-period analysis for the occurrence of LAE in 17 SQTS patients who received long-term HQ; and 2) a comparison of the annual incidence of LAE off- and on-HQ in 16 SQTS patients who survived a cardiac arrest. Results A total of 17 patients (82% male, age 29 ± 3 years, QTc before treatment 331 ± 3 ms) received HQ therapy (584 ± 53 mg/day). Therapy was stopped in 2 cases (12%) due to gastrointestinal intolerance, and 15 patients continued treatment for 6 ± 1 year. QTc prolongation was observed in all patients (by 60 ± 6 ms; p < 0.001). We compared the occurrence of LAE during 6 ± 1 years before and after HQ, observing that patients on HQ experienced a reduction in both the rate of LAE from 40% to 0% (p = 0.03) and the number of LAE per patient from 0.73 ± 0.3 to 0 (p = 0.026). Furthermore, the annual rate of LAE in the 16 patients with a previous cardiac arrest dropped from 12% before HQ to 0 on therapy (p = 0.028). Conclusions We demonstrated for the first time that treatment with HQ was associated with a lower incidence of LAE in SQTS patients. These data point to the importance that quinidine, that in several countries has been removed from the market, remains available worldwide for patients with SQTS. In the present study, therapy with HQ has been proven to be safe, with a relatively low rate of side effects.

Published
2017

35. Gene-specific therapy with mexiletine reduces arrhythmic events in patients with long QT syndrome type 3

Author

Mazzanti, A, Maragna, R, Faragli, A, Monteforte, N, Bloise, R, Memmi, M, Novelli, V, Baiardi, P, Bagnardi, V, Etheridge, S, Napolitano, C, Priori, S, Priori, S., BAGNARDI, VINCENZO, Mazzanti, A, Maragna, R, Faragli, A, Monteforte, N, Bloise, R, Memmi, M, Novelli, V, Baiardi, P, Bagnardi, V, Etheridge, S, Napolitano, C, Priori, S, Priori, S., and BAGNARDI, VINCENZO

Abstract

Background Long QT syndrome type 3 (LQT3) is a lethal disease caused by gain-of-function mutations in the SCN5A gene, coding for the alpha-subunit of the sodium channel NaV1.5. Mexiletine is used to block late sodium current and to shorten QT interval in LQT3 patients. Objectives The aim of this study was to determine whether mexiletine prevents arrhythmic events (arrhythmic syncope, aborted cardiac arrest, or sudden cardiac death) in LQT3 patients. Methods The endpoint of this retrospective cohort study, which studied consecutive LQT3 patients who were referred to our center and treated with mexiletine, was to evaluate the antiarrhythmic efficacy of mexiletine by comparing the number of arrhythmic events per patient and the annual rate of arrhythmic events during observation periods of equal duration before and after the beginning of therapy with mexiletine. Results The study population comprised 34 LQT3 patients, 19 (56%) of whom were male. The median age at beginning of treatment with mexiletine was 22 years, and median QTc interval before therapy 509 ms. The median duration of oral mexiletine therapy was 36 months, at an average daily dose of 8 ± 0.5 mg/kg. Mexiletine significantly shortened QTc (by 63 ± 6 ms; p < 0.0001) and reduced the percentage of patients with arrhythmic events (from 22% to 3%; p = 0.031), the mean number of arrhythmic events per patient (from 0.43 ± 0.17 to 0.03 ± 0.03; p = 0.027), and the annual rate of arrhythmic events (from 10.3% to 0.7%; p = 0.0097). Conclusions Besides shortening QTc interval, mexiletine caused a major reduction of life-threatening arrhythmic events in LQT3 patients, thus representing an efficacious therapeutic strategy.

Published
2016

39. Heparin in COVID-19 patients is associated with reduced in-hospital mortality: the multicentre Italian CORIST Study

Author

Walter Ageno, Raffaele Pesavento, Marinella Astuto, Katleen de Gaetano Donati, Francesca Santilli, Filippo Aucella, Eleonora Taddei, Marianna Meschiari, Laura Scorzolini, Biagio Pinchera, Giustino Parruti, Licia Iacoviello, Andrea Vianello, Gabriella Guarnieri, Arturo Montineri, Crizia Colombo, Carlo Signorelli, Lorenzo Blandi, Raffaele De Caterina, Maria Musso, Francesco Petri, Stefano Maitan, Anna Odone, Lucia Caiano, Francesca Crosta, Lorenzo Marra, Giuseppe Patti, Emanuela Pasi, Jovana Milic, Marco Olivieri, Claudia Colomba, Francesco Maria Fusco, Claudia Ravaglia, Alexandra Virano, Carlo Torti, Samir Al Moghazi, Venerino Poletti, Riccardo Maragna, Carlo Sanrocco, Sandro Mancarella, Greta Barbieri, Arturo Ciccullo, Leonardo Grisafi, Paola Simeone, Lorenzo Menicanti, Antonella Palimodde, Gloria Maccagni, Alessandra Vergori, Daniela Niola, Marco G. Mennuni, Gianpiero D'Offizi, Claudia Marotta, Damiano D'Ardes, Vincenzo Sangiovanni, Paolo Bonfanti, Giovanni Larizza, Francesco Di Gennaro, Alessandro Mengozzi, Massimo Mapelli, Giuseppe Di Tano, Laura Carrozzi, Antonella Agodi, Francesco Menichetti, Marialaura Bonaccio, Andrea Antinori, Marco Vinceti, Armando Leone, Franco Mastroianni, Silvia Marongiu, Filippo Minutolo, Giulio Maresca, Beatrice Molena, Nausicaa Berselli, Francesco Cipollone, Massimo Fantoni, Antonella Cingolani, Giovanni Guaraldi, Raffaella Sgariglia, Piergiuseppe Agostoni, Antonio Cascio, Maria Mazzitelli, Roberta Parisi, Augusto Di Castelnuovo, Gian Battista Danzi, Luca Aiello, Roberto Vettor, Elvira Grandone, Laura Vocciante, Emauele Graziani, Cristina Mussini, Marianna Rossi, Marco Rossato, Roberto Cauda, Rosa Arboretti, Alessandro Bartoloni, Simona Costanzo, Francesco Gianfagna, Andrea Rognoni, Ferruccio Madaro, Rossella Marcucci, Pasquale Abete, Francesco Cacciatore, Ivan Gentile, Di Castelnuovo, A, Costanzo, S, Antinori, A, Berselli, N, Blandi, L, Bonaccio, M, Cauda, R, Guaraldi, G, Menicanti, L, Mennuni, M, Parruti, G, Patti, G, Santilli, F, Signorelli, C, Vergori, A, Abete, P, Ageno, W, Agodi, A, Agostoni, P, Aiello, L, Al Moghazi, S, Arboretti, R, Astuto, M, Aucella, F, Barbieri, G, Bartoloni, A, Bonfanti, P, Cacciatore, F, Caiano, L, Carrozzi, L, Cascio, A, Ciccullo, A, Cingolani, A, Cipollone, F, Colomba, C, Colombo, C, Crosta, F, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Tano, G, D'Offizi, G, Fantoni, M, Fusco, F, Gentile, I, Gianfagna, F, Grandone, E, Graziani, E, Grisafi, L, Guarnieri, G, Larizza, G, Leone, A, Maccagni, G, Madaro, F, Maitan, S, Mancarella, S, Mapelli, M, Maragna, R, Marcucci, R, Maresca, G, Marongiu, S, Marotta, C, Marra, L, Mastroianni, F, Mazzitelli, M, Mengozzi, A, Menichetti, F, Meschiari, M, Milic, J, Minutolo, F, Molena, B, Montineri, A, Mussini, C, Musso, M, Niola, D, Odone, A, Olivieri, M, Palimodde, A, Parisi, R, Pasi, E, Pesavento, R, Petri, F, Pinchera, B, Poletti, V, Ravaglia, C, Rognoni, A, Rossato, M, Rossi, M, Sangiovanni, V, Sanrocco, C, Scorzolini, L, Sgariglia, R, Simeone, P, Taddei, E, Torti, C, Vettor, R, Vianello, A, Vinceti, M, Virano, A, Vocciante, L, De Caterina, R, Iacoviello, L, Danzi, G. B, De Gaetano Donati, K, Fusco, F. M, Simeone, P. G, Iacoviello, L., Di Castelnuovo, Augusto, Costanzo, Simona, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bonaccio, Marialaura, Cauda, Roberto, Guaraldi, Giovanni, Menicanti, Lorenzo, Mennuni, Marco, Parruti, Giustino, Patti, Giuseppe, Santilli, Francesca, Signorelli, Carlo, Vergori, Alessandra, Abete, Pasquale, Ageno, Walter, Agodi, Antonella, Agostoni, Piergiuseppe, Aiello, Luca, Al Moghazi, Samir, Arboretti, Rosa, Astuto, Marinella, Aucella, Filippo, Barbieri, Greta, Bartoloni, Alessandro, Bonfanti, Paolo, Cacciatore, Francesco, Caiano, Lucia, Carrozzi, Laura, Cascio, Antonio, Ciccullo, Arturo, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Colombo, Crizia, Crosta, Francesca, Danzi, Gian Battista, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Tano, Giuseppe, D'Offizi, Gianpiero, Fantoni, Massimo, Fusco, Francesco Maria, Gentile, Ivan, Gianfagna, Francesco, Grandone, Elvira, Graziani, Emauele, Grisafi, Leonardo, Guarnieri, Gabriella, Larizza, Giovanni, Leone, Armando, Maccagni, Gloria, Madaro, Ferruccio, Maitan, Stefano, Mancarella, Sandro, Mapelli, Massimo, Maragna, Riccardo, Marcucci, Rossella, Maresca, Giulio, Marongiu, Silvia, Marotta, Claudia, Marra, Lorenzo, Mastroianni, Franco, Mazzitelli, Maria, Mengozzi, Alessandro, Menichetti, Francesco, Meschiari, Marianna, Milic, Jovana, Minutolo, Filippo, Molena, Beatrice, Montineri, Arturo, Mussini, Cristina, Musso, Maria, Niola, Daniela, Odone, Anna, Olivieri, Marco, Palimodde, Antonella, Parisi, Roberta, Pasi, Emanuela, Pesavento, Raffaele, Petri, Francesco, Pinchera, Biagio, Poletti, Venerino, Ravaglia, Claudia, Rognoni, Andrea, Rossato, Marco, Rossi, Marianna, Sangiovanni, Vincenzo, Sanrocco, Carlo, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola Giustina, Taddei, Eleonora, Torti, Carlo, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, Virano, Alexandra, Vocciante, Laura, De Caterina, Raffaele, Iacoviello, Licia, Di Castelnuovo A., Costanzo S., Antinori A., Berselli N., Blandi L., Bonaccio M., Cauda R., Guaraldi G., Menicanti L., Mennuni M., Parruti G., Patti G., Santilli F., Signorelli C., Vergori A., Abete P., Ageno W., Agodi A., Agostoni P., Aiello L., Al Moghazi S., Arboretti R., Astuto M., Aucella F., Barbieri G., Bartoloni A., Bonfanti P., Cacciatore F., Caiano L., Carrozzi L., Cascio A., Ciccullo A., Cingolani A., Cipollone F., Colomba C., Colombo C., Crosta F., Danzi G.B., D'Ardes D., De Gaetano Donati K., Di Gennaro F., Di Tano G., D'Offizi G., Fantoni M., Fusco F.M., Gentile I., Gianfagna F., Grandone E., Graziani E., Grisafi L., Guarnieri G., Larizza G., Leone A., MacCagni G., Madaro F., Maitan S., Mancarella S., Mapelli M., Maragna R., Marcucci R., Maresca G., Marongiu S., Marotta C., Marra L., Mastroianni F., Mazzitelli M., Mengozzi A., Menichetti F., Meschiari M., Milic J., Minutolo F., Molena B., Montineri A., Mussini C., Musso M., Niola D., Odone A., Olivieri M., Palimodde A., Parisi R., Pasi E., Pesavento R., Petri F., Pinchera B., Poletti V., Ravaglia C., Rognoni A., Rossato M., Rossi M., Sangiovanni V., Sanrocco C., Scorzolini L., Sgariglia R., Simeone P.G., Taddei E., Torti C., Vettor R., Vianello A., Vinceti M., Virano A., Vocciante L., De Caterina R., and Iacoviello L.

Subjects
Male, medicine.medical_specialty, Settore MED/17 - Malattie Infettive, coronavirus, heparin, 030204 cardiovascular system & hematology, Lower risk, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Clinical endpoint, medicine, Humans, Thrombophilia, 030212 general & internal medicine, Hospital Mortality, Blood Coagulation, Survival analysis, Aged, Retrospective Studies, treatment, business.industry, Heparin, Mortality rate, COVID-19,mortality, Low-Molecular-Weight, Anticoagulants, COVID-19, Retrospective cohort study, Hematology, Heparin, Low-Molecular-Weight, Middle Aged, mortality, Survival Analysis, COVID-19 Drug Treatment, coagulation activation, coronaviru, Italy, treatments, Propensity score matching, Female, business, medicine.drug
Abstract

Introduction A hypercoagulable condition was described in patients with coronavirus disease 2019 (COVID-19) and proposed as a possible pathogenic mechanism contributing to disease progression and lethality. Aim We evaluated if in-hospital administration of heparin improved survival in a large cohort of Italian COVID-19 patients. Methods In a retrospective observational study, 2,574 unselected patients hospitalized in 30 clinical centers in Italy from February 19, 2020 to June 5, 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection were analyzed. The primary endpoint in a time-to event analysis was in-hospital death, comparing patients who received heparin (low-molecular-weight heparin [LMWH] or unfractionated heparin [UFH]) with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores. Results Out of 2,574 COVID-19 patients, 70.1% received heparin. LMWH was largely the most used formulation (99.5%). Death rates for patients receiving heparin or not were 7.4 and 14.0 per 1,000 person-days, respectively. After adjustment for propensity scores, we found a 40% lower risk of death in patients receiving heparin (hazard ratio = 0.60; 95% confidence interval: 0.49–0.74; E-value = 2.04). This association was particularly evident in patients with a higher severity of disease or strong coagulation activation. Conclusion In-hospital heparin treatment was associated with a lower mortality, particularly in severely ill COVID-19 patients and in those with strong coagulation activation. The results from randomized clinical trials are eagerly awaited to provide clear-cut recommendations.

Published
2021
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40. Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering

Author

Anna Sabena, Gabriele Giuliano, Raffaele Bruno, Francesco Cacciatore, Carlo Torti, Silvia Marongiu, Gloria Maccagni, Claudia Marotta, Giovanni Larizza, Francesco Petri, Massimo Mapelli, Giulio Maresca, Giulia Righetti, Alessandra Vergori, Ilaria Rossi, Damiano D'Ardes, Nicola Schiano Moriello, Ivan Gentile, Enrica Tamburrini, Luca Aiello, Piergiuseppe Agostoni, Antonio Cascio, Jovana Milic, Carlo Andrea Pivato, Agostino Virdis, Stefano Maitan, Francesco Cannata, Simona Costanzo, Carlo Signorelli, Franco Mastroianni, Federica Magni, Crizia Colombo, Giulio G. Stefanini, Lucia Caiano, Francesca Crosta, Lorenzo Marra, Giuseppe Patti, Katleen de Gaetano Donati, Valerio Langella, Annalisa Crisetti, Filippo Aucella, Antonella Cingolani, Francesco Salinaro, Augusto Di Castelnuovo, Giacomo Castiglione, Alessandro Gialluisi, Anna Odone, Cristina Mussini, Samir Al Moghazi, Lorenzo Blandi, Maria Musso, Marialaura Bonaccio, Raffaele De Caterina, Marco Olivieri, Roberto Cauda, Emanuela Pasi, Arturo Ciccullo, Stefano Perlini, Claudia Colomba, Antonella Palimodde, Gianpiero D'Offizi, Marco G. Mennuni, Walter Ageno, Raffaele Pesavento, Rosa Manuele, Roberta Mussinelli, Vincenzo Sangiovanni, Paolo Bonfanti, Andrea Antinori, Francesco Gianfagna, Andrea Rognoni, Laura Scorzolini, Riccardo Maragna, Rossella Marcucci, Filippo Minutolo, Armando Leone, Giustino Parruti, Licia Iacoviello, Lorenzo Menicanti, Sandro Mancarella, Rosa Arboretti, Greta Barbieri, Carlo Gaudiosi, Marco Rossato, Claudia Ravaglia, Andrea Vianello, Marianna Rossi, Emauele Graziani, Martina Barchitta, Giovanni Guaraldi, Enrico Maria Trecarichi, Gian Battista Danzi, Francesco Cipollone, Carlo Sanrocco, Marco Vinceti, Francesca Santilli, Marianna Meschiari, Gabriella Guarnieri, Antonella Agodi, Roberto Vettor, Raffaella Sgariglia, Ilaria My, Francesco Di Gennaro, Alessandro Mengozzi, Giuseppe Di Tano, Laura Carrozzi, Michele Spinicci, Venerino Poletti, Paola Simeone, Nausicaa Berselli, Francesco Maria Fusco, Di Castelnuovo A., Gialluisi A., Antinori A., Berselli N., Blandi L., Bonaccio M., Bruno R., Cauda R., Costanzo S., Guaraldi G., Menicanti L., Mennuni M., My I., Parruti G., Patti G., Perlini S., Santilli F., Signorelli C., Stefanini G., Vergori A., Ageno W., Agodi A., Agostoni P., Aiello L., Moghazi S.A., Arboretti R., Aucella F., Barbieri G., Barchitta M., Bonfanti P., Cacciatore F., Caiano L., Cannata F., Carrozzi L., Cascio A., Castiglione G., Cicullo A., Cingolani A., Cipollone F., Colomba C., Colombo C., Crisetti A., Crosta F., Danzi G.B., D'Ardes D., de Gaetano Donati K., Di Gennaro F., Di Tano G., D'Offizi G., Fusco F.M., Gaudiosi C., Gentile I., Gianfagna F., Giuliano G., Graziani E., Guarnieri G., Langella V., Larizza G., Leone A., Maccagni G., Magni F., Maitan S., Mancarella S., Manuele R., Mapelli M., Maragna R., Marcucci R., Maresca G., Marongiu S., Marotta C., Marra L., Mastroianni F., Mengozzi A., Meschiari M., Milic J., Minutolo F., Mussinelli R., Mussini C., Musso M., Odone A., Olivieri M., Palimodde A., Pasi E., Pesavento R., Petri F., Pivato C.A., Poletti V., Ravaglia C., Righetti G., Rognoni A., Rossato M., Rossi I., Rossi M., Sabena A., Salinaro F., Sangiovanni V., Sanrocco C., Moriello N.S., Scorzolini L., Sgariglia R., Simeone P.G., Spinicci M., Tamburrini E., Torti C., Trecarichi E.M., Vettor R., Vianello A., Vinceti M., Virdis A., de Caterina R., Iacoviello L., Di Castelnuovo, A, Gialluisi, A, Antinori, A, Berselli, N, Blandi, L, Bonaccio, M, Bruno, R, Cauda, R, Costanzo, S, Guaraldi, G, Menicanti, L, Mennuni, M, My, I, Parruti, G, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Stefanini, G, Vergori, A, Ageno, W, Agodi, A, Agostoni, P, Aiello, L, Al Moghazi, S, Arboretti, R, Aucella, F, Barbieri, G, Barchitta, M, Bonfanti, P, Cacciatore, F, Caiano, L, Cannata, F, Carrozzi, L, Cascio, A, Castiglione, G, Cicullo, A, Cingolani, A, Cipollone, F, Colomba, C, Colombo, C, Crisetti, A, Crosta, F, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Tano, G, D'Offizi, G, Fusco, F, Gaudiosi, C, Gentile, I, Gianfagna1, F, Giuliano, G, Graziani, E, Guarnieri, G, Langella, V, Larizza, G, Leone, A, Maccagni, G, Magni, F, Maitan, S, Mancarella, S, Manuele, R, Mapelli, M, Maragna, R, Marcucci, R, Maresca, G, Marongiu, S, Marotta, C, Marra, L, Mastroianni, F, Mengozzi, A, Meschiari, M, Milic, J, Minutolo, F, Mussinelli, R, Mussini, C, Musso, M, Odone, A, Olivieri, M, Palimodde, A, Pasi, E, Pesavento, R, Petri, F, Pivato, C, Poletti, V, Ravaglia, C, Righetti, G, Rognoni, A, Rossato, M, Rossi, I, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Schiano Moriello, N, Scorzolini, L, Sgariglia, R, Simeone, P, Spinicci, M, Tamburrini, E, Torti, C, Trecarichi, E, Vettor, R, Vianello, A, Vinceti, M, Virdis, A, De Caterina, R, Iacoviello, L, Di Castelnuovo, A., Gialluisi, A., Antinori, A., Berselli, N., Blandi, L., Bonaccio, M., Bruno, R., Cauda, R., Costanzo, S., Guaraldi, G., Menicanti, L., Mennuni, M., My, I., Parruti, G., Patti, G., Perlini, S., Santilli, F., Signorelli, C., Stefanini, G., Vergori, A., Ageno, W., Agodi, A., Agostoni, P., Aiello, L., Moghazi, S. A., Arboretti, R., Aucella, F., Barbieri, G., Barchitta, M., Bonfanti, P., Cacciatore, F., Caiano, L., Cannata, F., Carrozzi, L., Cascio, A., Castiglione, G., Cicullo, A., Cingolani, A., Cipollone, F., Colomba, C., Colombo, C., Crisetti, A., Crosta, F., Danzi, G. B., D’Ardes, D., de Gaetano Donati, K., Di Gennaro, F., Di Tano, G., D’Offizi, G., Fusco, F. M., Gaudiosi, C., Gentile, I., Gianfagna, F., Giuliano, G., Graziani, E., Guarnieri, G., Langella, V., Larizza, G., Leone, A., Maccagni, G., Magni, F., Maitan, S., Mancarella, S., Manuele, R., Mapelli, M., Maragna, R., Marcucci, R., Maresca, G., Marongiu, S., Marotta, C., Marra, L., Mastroianni, F., Mengozzi, A., Meschiari, M., Milic, J., Minutolo, F., Mussinelli, R., Mussini, C., Musso, M., Odone, A., Olivieri, M., Palimodde, A., Pasi, E., Pesavento, R., Petri, F., Pivato, C. A., Poletti, V., Ravaglia, C., Righetti, G., Rognoni, A., Rossato, M., Rossi, I., Rossi, M., Sabena, A., Salinaro, F., Sangiovanni, V., Sanrocco, C., Moriello, N. S., Scorzolini, L., Sgariglia, R., Simeone, P. G., Spinicci, M., Tamburrini, E., Torti, C., Trecarichi, E. M., Vettor, R., Vianello, A., Vinceti, M., Virdis, A., de Caterina, R., and Iacoviello, L.

Subjects
Male, Medicine (General), Antimalarial, 030204 cardiovascular system & hematology, Severity of Illness Index, Hospital Mortality, 0302 clinical medicine, Retrospective Studie, 80 and over, Cluster Analysis, 030212 general & internal medicine, Aged, Aged, 80 and over, Antimalarials, COVID-19, Female, Humans, Hydroxychloroquine, Italy, Middle Aged, Retrospective Studies, SARS-CoV-2, Treatment Outcome, Biotechnology, medicine.drug, Research Article, medicine.medical_specialty, Article Subject, Biomedical Engineering, Renal function, Health Informatics, 03 medical and health sciences, R5-920, Internal medicine, Diabetes mellitus, Severity of illness, medicine, Medical technology, R855-855.5, Cluster Analysi, business.industry, Cancer, Retrospective cohort study, medicine.disease, Obesity, COVID-19 Drug Treatment, Surgery, Observational study, business
Abstract

The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February–May 2020). Patients’ characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR[CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster∗HCQ interaction ( p < 0.001 ). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment.

Published
2021
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41. Lopinavir/ritonavir and darunavir/cobicistat in hospitalized covid-19 patients: Findings from the multicenter italian corist study

Author

Augusto Di Castelnuovo, Simona Costanzo, Andrea Antinori, Nausicaa Berselli, Lorenzo Blandi, Marialaura Bonaccio, Raffaele Bruno, Roberto Cauda, Alessandro Gialluisi, Giovanni Guaraldi, Lorenzo Menicanti, Marco Mennuni, Ilaria My, Agostino Parruti, Giuseppe Patti, Stefano Perlini, Francesca Santilli, Carlo Signorelli, Giulio G. Stefanini, Alessandra Vergori, Walter Ageno, Luca Aiello, Piergiuseppe Agostoni, Samir Al Moghazi, Rosa Arboretti, Filippo Aucella, Greta Barbieri, Martina Barchitta, Alessandro Bartoloni, Carolina Bologna, Paolo Bonfanti, Lucia Caiano, Laura Carrozzi, Antonio Cascio, Giacomo Castiglione, Mauro Chiarito, Arturo Ciccullo, Antonella Cingolani, Francesco Cipollone, Claudia Colomba, Crizia Colombo, Francesco Crosta, Giovanni Dalena, Chiara Dal Pra, Gian Battista Danzi, Damiano D'Ardes, Katleen de Gaetano Donati, Francesco Di Gennaro, Giuseppe Di Tano, Gianpiero D'Offizi, Tommaso Filippini, Francesco Maria Fusco, Carlo Gaudiosi, Ivan Gentile, Giancarlo Gini, Elvira Grandone, Gabriella Guarnieri, Gennaro L. F. Lamanna, Giovanni Larizza, Armando Leone, Veronica Lio, Angela Raffaella Losito, Gloria Maccagni, Stefano Maitan, Sandro Mancarella, Rosa Manuele, Massimo Mapelli, Riccardo Maragna, Lorenzo Marra, Giulio Maresca, Claudia Marotta, Franco Mastroianni, Maria Mazzitelli, Alessandro Mengozzi, Francesco Menichetti, Jovana Milic, Filippo Minutolo, Beatrice Molena, R. Mussinelli, Cristina Mussini, Maria Musso, Anna Odone, Marco Olivieri, Emanuela Pasi, Annalisa Perroni, Francesco Petri, Biagio Pinchera, Carlo A. Pivato, Venerino Poletti, Claudia Ravaglia, Marco Rossato, Marianna Rossi, Anna Sabena, Francesco Salinaro, Vincenzo Sangiovanni, Carlo Sanrocco, Laura Scorzolini, Raffaella Sgariglia, Paola Giustina Simeone, Michele Spinicci, Enrico Maria Trecarichi, Giovanni Veronesi, Roberto Vettor, Andrea Vianello, Marco Vinceti, Elena Visconti, Laura Vocciante, Raffaele De Caterina, Licia Iacoviello, The COVID-19 RISK and Treatments (CORIST) Collaboration, Di Castelnuovo, Augusto, Costanzo, Simona, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bonaccio, Marialaura, Bruno, Raffaele, Cauda, Roberto, Gialluisi, Alessandro, Guaraldi, Giovanni, Menicanti, Lorenzo, Mennuni, Marco, My, Ilaria, Parruti, Agostino, Patti, Giuseppe, Perlini, Stefano, Santilli, Francesca, Signorelli, Carlo, Stefanini, Giulio G, Vergori, Alessandra, Ageno, Walter, Aiello, Luca, Agostoni, Piergiuseppe, Al Moghazi, Samir, Arboretti, Rosa, Aucella, Filippo, Barbieri, Greta, Barchitta, Martina, Bartoloni, Alessandro, Bologna, Carolina, Bonfanti, Paolo, Caiano, Lucia, Carrozzi, Laura, Cascio, Antonio, Castiglione, Giacomo, Chiarito, Mauro, Ciccullo, Arturo, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Colombo, Crizia, Crosta, Francesco, Dalena, Giovanni, Dal Pra, Chiara, Danzi, Gian Battista, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Tano, Giuseppe, D'Offizi, Gianpiero, Filippini, Tommaso, Maria Fusco, Francesco, Gaudiosi, Carlo, Gentile, Ivan, Gini, Giancarlo, Grandone, Elvira, Guarnieri, Gabriella, Lamanna, Gennaro L F, Larizza, Giovanni, Leone, Armando, Lio, Veronica, Losito, Angela Raffaella, Maccagni, Gloria, Maitan, Stefano, Mancarella, Sandro, Manuele, Rosa, Mapelli, Massimo, Maragna, Riccardo, Marra, Lorenzo, Maresca, Giulio, Marotta, Claudia, Mastroianni, Franco, Mazzitelli, Maria, Mengozzi, Alessandro, Menichetti, Francesco, Milic, Jovana, Minutolo, Filippo, Molena, Beatrice, Mussinelli, R, Mussini, Cristina, Musso, Maria, Odone, Anna, Olivieri, Marco, Pasi, Emanuela, Perroni, Annalisa, Petri, Francesco, Pinchera, Biagio, Pivato, Carlo A, Poletti, Venerino, Ravaglia, Claudia, Rossato, Marco, Rossi, Marianna, Sabena, Anna, Salinaro, Francesco, Sangiovanni, Vincenzo, Sanrocco, Carlo, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola Giustina, Spinicci, Michele, Trecarichi, Enrico Maria, Veronesi, Giovanni, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, Visconti, Elena, Vocciante, Laura, De Caterina, Raffaele, Iacoviello, Licia, Di Castelnuovo, A, Costanzo, S, Antinori, A, Berselli, N, Blandi, L, Bonaccio, M, Bruno, R, Cauda, R, Gialluisi, A, Guaraldi, G, Menicanti, L, Mennuni, M, My, I, Parruti, A, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Stefanini, G, Vergori, A, Ageno, W, Aiello, L, Agostoni, P, Al Moghazi, S, Arboretti, R, Aucella, F, Barbieri, G, Barchitta, M, Bartoloni, A, Bologna, C, Bonfanti, P, Caiano, L, Carrozzi, L, Cascio, A, Castiglione, G, Chiarito, M, Ciccullo, A, Cingolani, A, Cipollone, F, Colomba, C, Colombo, C, Crosta, F, Dalena, G, Dal Pra, C, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Tano, G, D'Offizi, G, Filippini, T, Maria Fusco, F, Gaudiosi, C, Gentile, I, Gini, G, Grandone, E, Guarnieri, G, Lamanna, G, Larizza, G, Leone, A, Lio, V, Losito, A, Maccagni, G, Maitan, S, Mancarella, S, Manuele, R, Mapelli, M, Maragna, R, Marra, L, Maresca, G, Marotta, C, Mastroianni, F, Mazzitelli, M, Mengozzi, A, Menichetti, F, Milic, J, Minutolo, F, Molena, B, Mussini, C, Musso, M, Odone, A, Olivieri, M, Pasi, E, Perroni, A, Petri, F, Pinchera, B, Pivato, C, Poletti, V, Ravaglia, C, Rossato, M, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Scorzolini, L, Sgariglia, R, Simeone, P, Spinicci, M, Trecarichi, E, Veronesi, G, Vettor, R, Vianello, A, Vinceti, M, Visconti, E, Vocciante, L, De Caterina, R, Iacoviello, L, Di Castelnuovo, A., Costanzo, S., Antinori, A., Berselli, N., Blandi, L., Bonaccio, M., Bruno, R., Cauda, R., Gialluisi, A., Guaraldi, G., Menicanti, L., Mennuni, M., My, I., Parruti, A., Patti, G., Perlini, S., Santilli, F., Signorelli, C., Stefanini, G. G., Vergori, A., Ageno, W., Aiello, L., Agostoni, P., Moghazi, S. A., Arboretti, R., Aucella, F., Barbieri, G., Barchitta, M., Bartoloni, A., Bologna, C., Bonfanti, P., Caiano, L., Carrozzi, L., Cascio, A., Castiglione, G., Chiarito, M., Ciccullo, A., Cingolani, A., Cipollone, F., Colomba, C., Colombo, C., Crosta, F., Dalena, G., Dal Pra, C., Danzi, G. B., D'Ardes, D., Donati, K. G., Di Gennaro, F., Di Tano, G., D'Offizi, G., Filippini, T., Fusco, F. M., Gaudiosi, C., Gentile, I., Gini, G., Grandone, E., Guarnieri, G., Lamanna, G. L. F., Larizza, G., Leone, A., Lio, V., Losito, A. R., Maccagni, G., Maitan, S., Mancarella, S., Manuele, R., Mapelli, M., Maragna, R., Marra, L., Maresca, G., Marotta, C., Mastroianni, F., Mazzitelli, M., Mengozzi, A., Menichetti, F., Milic, J., Minutolo, F., Molena, B., Mussinelli, R., Mussini, C., Musso, M., Odone, A., Olivieri, M., Pasi, E., Perroni, A., Petri, F., Pinchera, B., Pivato, C. A., Poletti, V., Ravaglia, C., Rossato, M., Rossi, M., Sabena, A., Salinaro, F., Sangiovanni, V., Sanrocco, C., Scorzolini, L., Sgariglia, R., Simeone, P. G., Spinicci, M., Trecarichi, E. M., Veronesi, G., Vettor, R., Vianello, A., Vinceti, M., Visconti, E., Vocciante, L., Caterina, R. D., Iacoviello, L., Di Castelnuovo A., Costanzo S., Antinori A., Berselli N., Blandi L., Bonaccio M., Bruno R., Cauda R., Gialluisi A., Guaraldi G., Menicanti L., Mennuni M., My I., Parruti A., Patti G., Perlini S., Santilli F., Signorelli C., Stefanini G.G., Vergori A., Ageno W., Aiello L., Agostoni P., Moghazi S.A., Arboretti R., Aucella F., Barbieri G., Barchitta M., Bartoloni A., Bologna C., Bonfanti P., Caiano L., Carrozzi L., Cascio A., Castiglione G., Chiarito M., Ciccullo A., Cingolani A., Cipollone F., Colomba C., Colombo C., Crosta F., Dalena G., Dal Pra C., Danzi G.B., D'ardes D., Donati K.G., Di Gennaro F., Di Tano G., D'offizi G., Filippini T., Fusco F.M., Gaudiosi C., Gentile I., Gini G., Grandone E., Guarnieri G., Lamanna G.L.F., Larizza G., Leone A., Lio V., Losito A.R., Maccagni G., Maitan S., Mancarella S., Manuele R., Mapelli M., Maragna R., Marra L., Maresca G., Marotta C., Mastroianni F., Mazzitelli M., Mengozzi A., Menichetti F., Milic J., Minutolo F., Molena B., Mussinelli R., Mussini C., Musso M., Odone A., Olivieri M., Pasi E., Perroni A., Petri F., Pinchera B., Pivato C.A., Poletti V., Ravaglia C., Rossato M., Rossi M., Sabena A., Salinaro F., Sangiovanni V., Sanrocco C., Scorzolini L., Sgariglia R., Simeone P.G., Spinicci M., Trecarichi E.M., Veronesi G., Vettor R., Vianello A., Vinceti M., Visconti E., Vocciante L., Caterina R.D., and Iacoviello L.

Subjects
Medicine (General), medicine.medical_specialty, Lopinavir/ritonavir, Lopinavir, R5-920, Internal medicine, medicine, Darunavir, Original Research, COVID-19, In-hospital mortality, SARS-CoV-2, darunavir, in-hospital mortality, lopinavir, business.industry, Cobicistat, Mortality rate, General Medicine, medicine.disease, Propensity score matching, Medicine, Ritonavir, business, medicine.drug, Kidney disease
Abstract

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients.Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients.Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores.Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs.Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients.

Published
2021

42. Common cardiovascular risk factors and in-hospital mortality in 3,894 patients with COVID-19: survival analysis and machine learning-based findings from the multicentre Italian CORIST Study

Author

Augusto Di Castelnuovo, Marialaura Bonaccio, Simona Costanzo, Alessandro Gialluisi, Andrea Antinori, Nausicaa Berselli, Lorenzo Blandi, Raffaele Bruno, Roberto Cauda, Giovanni Guaraldi, Ilaria My, Lorenzo Menicanti, Giustino Parruti, Giuseppe Patti, Stefano Perlini, Francesca Santilli, Carlo Signorelli, Giulio G. Stefanini, Alessandra Vergori, Amina Abdeddaim, Walter Ageno, Antonella Agodi, Piergiuseppe Agostoni, Luca Aiello, Samir Al Moghazi, Filippo Aucella, Greta Barbieri, Alessandro Bartoloni, Carolina Bologna, Paolo Bonfanti, Serena Brancati, Francesco Cacciatore, Lucia Caiano, Francesco Cannata, Laura Carrozzi, Antonio Cascio, Antonella Cingolani, Francesco Cipollone, Claudia Colomba, Annalisa Crisetti, Francesca Crosta, Gian B. Danzi, Damiano D'Ardes, Katleen de Gaetano Donati, Francesco Di Gennaro, Gisella Di Palma, Giuseppe Di Tano, Massimo Fantoni, Tommaso Filippini, Paola Fioretto, Francesco M. Fusco, Ivan Gentile, Leonardo Grisafi, Gabriella Guarnieri, Francesco Landi, Giovanni Larizza, Armando Leone, Gloria Maccagni, Sandro Maccarella, Massimo Mapelli, Riccardo Maragna, Rossella Marcucci, Giulio Maresca, Claudia Marotta, Lorenzo Marra, Franco Mastroianni, Alessandro Mengozzi, Francesco Menichetti, Jovana Milic, Rita Murri, Arturo Montineri, Roberta Mussinelli, Cristina Mussini, Maria Musso, Anna Odone, Marco Olivieri, Emanuela Pasi, Francesco Petri, Biagio Pinchera, Carlo A. Pivato, Roberto Pizzi, Venerino Poletti, Francesca Raffaelli, Claudia Ravaglia, Giulia Righetti, Andrea Rognoni, Marco Rossato, Marianna Rossi, Anna Sabena, Francesco Salinaro, Vincenzo Sangiovanni, Carlo Sanrocco, Antonio Scarafino, Laura Scorzolini, Raffaella Sgariglia, Paola G. Simeone, Enrico Spinoni, Carlo Torti, Enrico M. Trecarichi, Francesca Vezzani, Giovanni Veronesi, Roberto Vettor, Andrea Vianello, Marco Vinceti, Raffaele De Caterina, Licia Iacoviello, Di Castelnuovo, A., Bonaccio, M., Costanzo, S., Gialluisi, A., Antinori, A., Berselli, N., Blandi, L., Bruno, R., Cauda, R., Guaraldi, G., My, I., Menicanti, L., Parruti, G., Patti, G., Perlini, S., Santilli, F., Signorelli, C., Stefanini, G. G., Vergori, A., Abdeddaim, A., Ageno, W., Agodi, A., Agostoni, P., Aiello, L., Al Moghazi, S., Aucella, F., Barbieri, G., Bartoloni, A., Bologna, C., Bonfanti, P., Brancati, S., Cacciatore, F., Caiano, L., Cannata, F., Carrozzi, L., Cascio, A., Cingolani, A., Cipollone, F., Colomba, C., Crisetti, A., Crosta, F., Danzi, G. B., D'Ardes, D., de Gaetano Donati, K., Di Gennaro, F., Di Palma, G., Di Tano, G., Fantoni, M., Filippini, T., Fioretto, P., Fusco, F. M., Gentile, I., Grisafi, L., Guarnieri, G., Landi, F., Larizza, G., Leone, A., Maccagni, G., Maccarella, S., Mapelli, M., Maragna, R., Marcucci, R., Maresca, G., Marotta, C., Marra, L., Mastroianni, F., Mengozzi, A., Menichetti, F., Milic, J., Murri, R., Montineri, A., Mussinelli, R., Mussini, C., Musso, M., Odone, A., Olivieri, M., Pasi, E., Petri, F., Pinchera, B., Pivato, C. A., Pizzi, R., Poletti, V., Raffaelli, F., Ravaglia, C., Righetti, G., Rognoni, A., Rossato, M., Rossi, M., Sabena, A., Salinaro, F., Sangiovanni, V., Sanrocco, C., Scarafino, A., Scorzolini, L., Sgariglia, R., Simeone, P. G., Spinoni, E., Torti, C., Trecarichi, E. M., Vezzani, F., Veronesi, G., Vettor, R., Vianello, A., Vinceti, M., De Caterina, R., Iacoviello, L., Di Castelnuovo, Augusto, Bonaccio, Marialaura, Costanzo, Simona, Gialluisi, Alessandro, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bruno, Raffaele, Cauda, Roberto, Guaraldi, Giovanni, My, Ilaria, Menicanti, Lorenzo, Parruti, Giustino, Patti, Giuseppe, Perlini, Stefano, Santilli, Francesca, Signorelli, Carlo, Stefanini, Giulio G, Vergori, Alessandra, Abdeddaim, Amina, Ageno, Walter, Agodi, Antonella, Agostoni, Piergiuseppe, Aiello, Luca, Al Moghazi, Samir, Aucella, Filippo, Barbieri, Greta, Bartoloni, Alessandro, Bologna, Carolina, Bonfanti, Paolo, Brancati, Serena, Cacciatore, Francesco, Caiano, Lucia, Cannata, Francesco, Carrozzi, Laura, Cascio, Antonio, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Crisetti, Annalisa, Crosta, Francesca, Danzi, Gian B, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Palma, Gisella, Di Tano, Giuseppe, Fantoni, Massimo, Filippini, Tommaso, Fioretto, Paola, Fusco, Francesco M, Gentile, Ivan, Grisafi, Leonardo, Guarnieri, Gabriella, Landi, Francesco, Larizza, Giovanni, Leone, Armando, Maccagni, Gloria, Maccarella, Sandro, Mapelli, Massimo, Maragna, Riccardo, Marcucci, Rossella, Maresca, Giulio, Marotta, Claudia, Marra, Lorenzo, Mastroianni, Franco, Mengozzi, Alessandro, Menichetti, Francesco, Milic, Jovana, Murri, Rita, Montineri, Arturo, Mussinelli, Roberta, Mussini, Cristina, Musso, Maria, Odone, Anna, Olivieri, Marco, Pasi, Emanuela, Petri, Francesco, Pinchera, Biagio, Pivato, Carlo A, Pizzi, Roberto, Poletti, Venerino, Raffaelli, Francesca, Ravaglia, Claudia, Righetti, Giulia, Rognoni, Andrea, Rossato, Marco, Rossi, Marianna, Sabena, Anna, Salinaro, Francesco, Sangiovanni, Vincenzo, Sanrocco, Carlo, Scarafino, Antonio, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola G, Spinoni, Enrico, Torti, Carlo, Trecarichi, Enrico M, Vezzani, Francesca, Veronesi, Giovanni, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, De Caterina, Raffaele, Iacoviello, Licia, Di Castelnuovo, A, Bonaccio, M, Costanzo, S, Gialluisi, A, Antinori, A, Berselli, N, Blandi, L, Bruno, R, Cauda, R, Guaraldi, G, My, I, Menicanti, L, Parruti, A, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Stefanini, G, Vergori, A, Abdeddaim, A, Ageno, W, Agodi, A, Agostoni, P, Aiello, L, Al Moghazi, S, Aucella, F, Barbieri, G, Bartoloni, A, Bologna, C, Bonfanti, P, Brancati, S, Cacciatore, F, Caiano, L, Cannata, F, Carrozzi, L, Cascio, A, Cingolani, A, Cipollone, F, Colomba, C, Crisetti, A, Crosta, F, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Palma, G, Di Tano, G, Fantoni, M, Filippini, T, Fioretto, P, Fusco, F, Gentile, I, Grisafi, L, Guarnieri, G, Landi, F, Larizza, G, Leone, A, Maccagni, G, Maccarella, S, Mapelli, M, Maragna, R, Marcucci, R, Maresca, G, Marotta, C, Marra, L, Mastroianni, F, Mengozzi, A, Menichetti, F, Milic, J, Miurri, R, Montineri, A, Mussinelli, R, Mussini, C, Musso, M, Odone, A, Olivieri, M, Pasi, E, Petri, F, Pinchera, B, Pivato, C, Pizzi, R, Poletti, V, Raffaelli, F, Ravaglia, C, Righetti, G, Rognoni, A, Rossato, M, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Scarafino, A, Scorzolini, L, Sgariglia, R, Simeone, P, Spinoni, E, Torti, C, Trecarichi, E, Vezzani, F, Veronesi, G, Vettor, R, Vianello, A, Vinceti, M, De Caterina, R, and Iacoviello, L

Subjects
Male, Epidemiology, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), 030204 cardiovascular system & hematology, computer.software_genre, Machine Learning, 0302 clinical medicine, Retrospective Studie, Risk Factors, Cardiovascular Disease, 80 and over, Medicine, Age Factor, Viral, Hospital Mortality, Betacoronavirus Hospital Mortality, Young adult, Aged, 80 and over, Nutrition and Dietetics, COVID-19, In-hospital mortality, Risk factors, Mortality rate, Hazard ratio, Age Factors, Middle Aged, C-Reactive Protein, Cardiovascular Diseases, Female, Survival Analysi, Cardiology and Cardiovascular Medicine, Coronavirus Infections, Human, Glomerular Filtration Rate, Adult, medicine.medical_specialty, Adolescent, Pneumonia, Viral, 030209 endocrinology & metabolism, Settore MED/17 - MALATTIE INFETTIVE, Machine learning, Aged, Humans, Pandemics, Retrospective Studies, SARS-CoV-2, Survival Analysis, Young Adult, Betacoronavirus, Article, 03 medical and health sciences, Risk factor, Survival analysis, Pandemic, Betacoronaviru, business.industry, Coronavirus Infection, Risk Factor, Retrospective cohort study, Pneumonia, Confidence interval, Artificial intelligence, business, computer
Abstract

Background and aims There is poor knowledge on characteristics, comorbidities and laboratory measures associated with risk for adverse outcomes and in-hospital mortality in European Countries. We aimed at identifying baseline characteristics predisposing COVID-19 patients to in-hospital death. Methods and results Retrospective observational study on 3894 patients with SARS-CoV-2 infection hospitalized from February 19th to May 23rd, 2020 and recruited in 30 clinical centres distributed throughout Italy. Machine learning (random forest)-based and Cox survival analysis. 61.7% of participants were men (median age 67 years), followed up for a median of 13 days. In-hospital mortality exhibited a geographical gradient, Northern Italian regions featuring more than twofold higher death rates as compared to Central/Southern areas (15.6% vs 6.4%, respectively). Machine learning analysis revealed that the most important features in death classification were impaired renal function, elevated C reactive protein and advanced age. These findings were confirmed by multivariable Cox survival analysis (hazard ratio (HR): 8.2; 95% confidence interval (CI) 4.6–14.7 for age ≥85 vs 18–44 y); HR = 4.7; 2.9–7.7 for estimated glomerular filtration rate levels, Highlights • Impaired renal function, elevated C-reactive protein and advanced age were major indicators of death in COVID-19 patients. • These associations were substantially homogenous across all sub-groups analysed. • No relation was found with obesity, tobacco use, cardiovascular disease and related-comorbidities. • Death rates were higher in the Northern as opposed to Central-Southern Italian regions.

Published
2020

43. Use of hydroxychloroquine in hospitalised COVID-19 patients is associated with reduced mortality: Findings from the observational multicentre Italian CORIST study

Author

Venerino Poletti, Damiano D'Ardes, Paola Simeone, Cristina Mussini, Giustino Parruti, Sandro Maccarella, Licia Iacoviello, Giulio G. Stefanini, Roberta Mussinelli, Vincenzo Sangiovanni, Paolo Bonfanti, Roberto Vettor, Andrea Vianello, Arturo Montineri, Roberto Cauda, Elvira Grandone, Maria Mazzitelli, Claudia Ravaglia, Marialaura Bonaccio, Giulio Maresca, Francesco Di Gennaro, Alessandro Mengozzi, Anna Sabena, Gian Battista Danzi, Giuseppe Di Tano, Emanuela Pasi, Ilaria Rossi, Lucia Caiano, Laura Carrozzi, Francesco Landi, Francesca Crosta, Tommaso Filippini, Francesco Menichetti, Piergiuseppe Agostoni, Andrea Madaro, Antonio Cascio, Carlo Signorelli, Michele Spinicci, Carlo Sanrocco, Enrico Guido Spinoni, Maria Musso, Alessandra Vergori, Lorenzo Marra, Giuseppe Patti, Laura Vocciante, Marco Olivieri, Francesca Santilli, Stefano Perlini, Claudia Colomba, Francesco Salinaro, Marianna Meschiari, Gabriella Guarnieri, Giampiero D'Offizi, Riccardo Maragna, Paola Del Giacomo, Giancarlo Gini, Katleen de Gaetano Donati, Andrea Antinori, Filippo Aucella, Raffaele De Caterina, Lorenzo Menicanti, Gloria Maccagni, Amedeo Venezia, Chiara Dal Pra, Carlo Andrea Pivato, Walter Ageno, Antonella Agodi, Francesco Cannata, Francesco Petri, Luca Aiello, Biagio Pinchera, Marinella Astuto, Raffaella Sgariglia, Giovanni Guaraldi, Marco Vinceti, Laura Scorzolini, Samir Al Moghazi, Armando Leone, Giovanni Veronesi, Arturo Ciccullo, Leonardo Grisafi, Francesco Cipollone, Massimo Mapelli, Greta Barbieri, Silvia Lamonica, Raffaele Bruno, Filippo Minutolo, Antonella Cingolani, Alessandro Gialluisi, Marco Rossato, Andrea Rognoni, Marianna Rossi, Claudia Marotta, Franco Mastroianni, Ilaria My, Enrico Maria Trecarichi, Anna Odone, Alessandro Bartoloni, Simona Costanzo, Francesco Cacciatore, Ivan Gentile, Massimo Rinaldi, Nausicaa Berselli, Francesco Maria Fusco, Augusto Di Castelnuovo, Lorenzo Blandi, Castelnuovo A.D., Costanzo S., Antinori A., Berselli N., Blandi L., Bruno R., Cauda R., Guaraldi G., Menicanti L., My I., Parruti G., Patti G., Perlini S., Santilli F., Signorelli C., Spinoni E., Stefanini G.G., Vergori A., Ageno W., Agodi A., Aiello L., Agostoni P., Moghazi S.A., Astuto M., Aucella F., Barbieri G., Bartoloni A., Bonaccio M., Bonfanti P., Cacciatore F., Caiano L., Cannata F., Carrozzi L., Cascio A., Ciccullo A., Cingolani A., Cipollone F., Colomba C., Crosta F., Pra C.D., Danzi G.B., D'Ardes D., Donati K.D.G., Giacomo P.D., Gennaro F.D., Di Tano G., D'Offizi G., Filippini T., Fusco F.M., Gentile I., Gialluisi A., Gini G., Grandone E., Grisafi L., Guarnieri G., Lamonica S., Landi F., Leone A., Maccagni G., Maccarella S., Madaro A., Mapelli M., Maragna R., Marra L., Maresca G., Marotta C., Mastroianni F., Mazzitelli M., Mengozzi A., Menichetti F., Meschiari M., Minutolo F., Montineri A., Mussinelli R., Mussini C., Musso M., Odone A., Olivieri M., Pasi E., Petri F., Pinchera B., Pivato C.A., Poletti V., Ravaglia C., Rinaldi M., Rognoni A., Rossato M., Rossi I., Rossi M., Sabena A., Salinaro F., Sangiovanni V., Sanrocco C., Scorzolini L., Sgariglia R., Simeone P.G., Spinicci M., Trecarichi E.M., Venezia A., Veronesi G., Vettor R., Vianello A., Vinceti M., Vocciante L., De Caterina R., Iacoviello L., Castelnuovo, A. D., Costanzo, S., Antinori, A., Berselli, N., Blandi, L., Bruno, R., Cauda, R., Guaraldi, G., Menicanti, L., My, I., Parruti, G., Patti, G., Perlini, S., Santilli, F., Signorelli, C., Spinoni, E., Stefanini, G. G., Vergori, A., Ageno, W., Agodi, A., Aiello, L., Agostoni, P., Moghazi, S. A., Astuto, M., Aucella, F., Barbieri, G., Bartoloni, A., Bonaccio, M., Bonfanti, P., Cacciatore, F., Caiano, L., Cannata, F., Carrozzi, L., Cascio, A., Ciccullo, A., Cingolani, A., Cipollone, F., Colomba, C., Crosta, F., Pra, C. D., Danzi, G. B., D'Ardes, D., Donati, K. D. G., Giacomo, P. D., Gennaro, F. D., Di Tano, G., D'Offizi, G., Filippini, T., Fusco, F. M., Gentile, I., Gialluisi, A., Gini, G., Grandone, E., Grisafi, L., Guarnieri, G., Lamonica, S., Landi, F., Leone, A., Maccagni, G., Maccarella, S., Madaro, A., Mapelli, M., Maragna, R., Marra, L., Maresca, G., Marotta, C., Mastroianni, F., Mazzitelli, M., Mengozzi, A., Menichetti, F., Meschiari, M., Minutolo, F., Montineri, A., Mussinelli, R., Mussini, C., Musso, M., Odone, A., Olivieri, M., Pasi, E., Petri, F., Pinchera, B., Pivato, C. A., Poletti, V., Ravaglia, C., Rinaldi, M., Rognoni, A., Rossato, M., Rossi, I., Rossi, M., Sabena, A., Salinaro, F., Sangiovanni, V., Sanrocco, C., Scorzolini, L., Sgariglia, R., Simeone, P. G., Spinicci, M., Trecarichi, E. M., Venezia, A., Veronesi, G., Vettor, R., Vianello, A., Vinceti, M., Vocciante, L., De Caterina, R., Iacoviello, L., Castelnuovo, A, Costanzo, S, Antinori, A, Berselli, N, Blandi, L, Bruno, R, Cauda, R, Guaraldi, G, Menicanti, L, My, I, Parruti, G, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Spinoni, E, Stefanini, G, Vergori, A, Ageno, W, Agodi, A, Aiello, L, Agostoni, P, Moghazi, S, Astuto, M, Aucella, F, Barbieri, G, Bartoloni, A, Bonaccio, M, Bonfanti, P, Cacciatore, F, Caiano, L, Cannata, F, Carrozzi, L, Cascio, A, Ciccullo, A, Cingolani, A, Cipollone, F, Colomba, C, Crosta, F, Pra, C, Danzi, G, D'Ardes, D, Donati, K, Giacomo, P, Gennaro, F, Tano, G, D'Offizi, G, Filippini, T, Fusco, F, Gentile, I, Gialluisi, A, Gini, G, Grandone, E, Grisafi, L, Guarnieri, G, Lamonica, S, Landi, F, Leone, A, Maccagni, G, Maccarella, S, Madaro, A, Mapelli, M, Maragna, R, Marra, L, Maresca, G, Marotta, C, Mastroianni, F, Mazzitelli, M, Mengozzi, A, Menichetti, F, Meschiari, M, Minutolo, F, Montineri, A, Mussinelli, R, Mussini, C, Musso, M, Odone, A, Olivieri, M, Pasi, E, Petri, F, Pinchera, B, Pivato, C, Poletti, V, Ravaglia, C, Rinaldi, M, Rognoni, A, Rossato, M, Rossi, I, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Scorzolini, L, Sgariglia, R, Simeone, P, Spinicci, M, Trecarichi, E, Venezia, A, Veronesi, G, Vettor, R, Vianello, A, Vinceti, M, Vocciante, L, De Caterina, R, and Iacoviello, L

Subjects
Male, medicine.medical_specialty, 030204 cardiovascular system & hematology, Lower risk, law.invention, COVID-19, Disease severity, Hydroxychloroquine, Inflammation, Mortality, Aged, Aged, 80 and over, Female, Hospital Mortality, Humans, Italy, Middle Aged, Retrospective Studies, Treatment Outcome, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Retrospective Studie, law, Internal medicine, 80 and over, Internal Medicine, medicine, 030212 general & internal medicine, Risk factor, business.industry, Mortality rate, Retrospective cohort study, COVID-19 Drug Treatment, Propensity score matching, Commentary, Observational study, business, Human, medicine.drug
Abstract

Background Hydroxychloroquine (HCQ) was proposed as potential treatment for COVID-19. Objective We set-up a multicenter Italian collaboration to investigate the relationship between HCQ therapy and COVID-19 in-hospital mortality. Methods In a retrospective observational study, 3,451 unselected patients hospitalized in 33 clinical centers in Italy, from February 19, 2020 to May 23, 2020, with laboratory-confirmed SARS-CoV-2 infection, were analyzed. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received HCQ with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores, with the addition of subgroup analyses. Results Out of 3,451 COVID-19 patients, 76.3% received HCQ. Death rates (per 1,000 person-days) for patients receiving or not HCQ were 8.9 and 15.7, respectively. After adjustment for propensity scores, we found 30% lower risk of death in patients receiving HCQ (HR=0.70; 95%CI: 0.59 to 0.84; E-value=1.67). Secondary analyses yielded similar results. The inverse association of HCQ with inpatient mortality was particularly evident in patients having elevated C-reactive protein at entry. Conclusions HCQ use was associated with a 30% lower risk of death in COVID-19 hospitalized patients. Within the limits of an observational study and awaiting results from randomized controlled trials, these data do not discourage the use of HCQ in inpatients with COVID-19.

Published
2020

44. RAAS inhibitors are not associated with mortality in COVID-19 patients: Findings from an observational multicenter study in Italy and a meta-analysis of 19 studies

Author

Francesca Santilli, Marianna Meschiari, Gabriella Guarnieri, Francesco Petri, Anna Sabena, Gloria Maccagni, Giovanni Larizza, Massimo Mapelli, Maria Mazzitelli, Gian Battista Danzi, Katleen de Gaetano Donati, Annalisa Crisetti, Jovana Milic, Raffaele Pesavento, Biagio Pinchera, Riccardo Maragna, Carlo Andrea Pivato, Lorenzo Menicanti, Francesco Maria Fusco, Luca Aiello, Sandro Mancarella, Carlo Sanrocco, Alessandra Vergori, Greta Barbieri, Filippo Aucella, Silvia Marongiu, Giulio Maresca, Marianna Rossi, Andrea Antinori, Venerino Poletti, Francesco Cacciatore, Giacomo Castiglione, Enrico Maria Trecarichi, Lucia Caiano, Francesca Crosta, Roberto Vettor, Francesco Menichetti, Maria Musso, Francesco Salinaro, Marco Olivieri, Stefano Perlini, Claudia Colomba, Crizia Colombo, Ottavia Cozzi, Stefano Maitan, Marialaura Bonaccio, Ilaria My, Alexandra Virano, Paola Simeone, Marco Vinceti, Antonella Cingolani, Gianpiero D'Offizi, Damiano D'Ardes, Claudia Marotta, M. B. Lucia, Carlo Signorelli, Lorenzo Marra, Giuseppe Patti, Raffaele De Caterina, Armando Leone, Veronica Lio, Beatrice Molena, Giustino Parruti, Giulio G. Stefanini, Licia Iacoviello, Laura Vocciante, Franco Mastroianni, Raffaella Sgariglia, Cristina Mussini, Francesco Cipollone, Marco Rossato, Lorenzo Blandi, Emanuela Pasi, Samir Al Moghazi, Andrea Vianello, Filippo Minutolo, Ivan Gentile, Giovanni Guaraldi, Rosa Manuele, Pasquale Abete, Arturo Ciccullo, Antonella Palimodde, Giancarlo Scoppettuolo, Walter Ageno, Marco G. Mennuni, Roberta Mussinelli, Vincenzo Sangiovanni, Roberto Cauda, Laura Scorzolini, Paolo Bonfanti, Alessandro Gialluisi, Stefania Cianfrone, Piergiuseppe Agostoni, Antonio Cascio, Simona Costanzo, Augusto Di Castelnuovo, Nausicaa Berselli, Rosa Arboretti, Emauele Graziani, Martina Barchitta, Anna Odone, Francesco Di Gennaro, Alessandro Mengozzi, Alessandro Bartoloni, Giuseppe Di Tano, Laura Carrozzi, Ferruccio Madaro, Rossella Marcucci, Claudia Ravaglia, Di Castelnuovo, Augusto, Costanzo, Simona, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bonaccio, Marialaura, Cauda, Roberto, Gialluisi, Alessandro, Guaraldi, Giovanni, Menicanti, Lorenzo, Mennuni, Marco, Mussinelli, Roberta, My, Ilaria, Parruti, Giustino, Patti, Giuseppe, Perlini, Stefano, Santilli, Francesca, Signorelli, Carlo, Stefanini, Giulio G., Vergori, Alessandra, Abete, Pasquale, Ageno, Walter, Agostoni, Piergiuseppe, Aiello, Luca, Al Moghazi, Samir, Arboretti, Rosa, Aucella, Filippo, Barbieri, Greta, Barchitta, Martina, Bartoloni, Alessandro, Bonfanti, Paolo, Cacciatore, Francesco, Caiano, Lucia, Carrozzi, Laura, Cascio, Antonio, Castiglione, Giacomo, Cianfrone, Stefania, Ciccullo, Arturo, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Colombo, Crizia, Cozzi, Ottavia, Crisetti, Annalisa, Crosta, Francesca, Danzi, Gian Battista, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Tano, Giuseppe, D'Offizi, Gianpiero, Fusco, Francesco Maria, Gentile, Ivan, Graziani, Emauele, Guarnieri, Gabriella, Larizza, Giovanni, Leone, Armando, Lio, Veronica, Lucia, Mothanje Barbara, Maccagni, Gloria, Madaro, Ferruccio, Maitan, Stefano, Mancarella, Sandro, Manuele, Rosa, Mapelli, Massimo, Maragna, Riccardo, Marcucci, Rossella, Maresca, Giulio, Marongiu, Silvia, Marotta, Claudia, Marra, Lorenzo, Mastroianni, Franco, Mazzitelli, Maria, Mengozzi, Alessandro, Menichetti, Francesco, Meschiari, Marianna, Milic, Jovana, Minutolo, Filippo, Molena, Beatrice, Mussini, Cristina, Musso, Maria, Odone, Anna, Olivieri, Marco, Palimodde, Antonella, Pasi, Emanuela, Pesavento, Raffaele, Petri, Francesco, Pinchera, Biagio, Pivato, Carlo A., Poletti, Venerino, Ravaglia, Claudia, Rossato, Marco, Rossi, Marianna, Sabena, Anna, Salinaro, Francesco, Sangiovanni, Vincenzo, Sanrocco, Carlo, Scoppettuolo, Giancarlo, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola Giustina, Trecarichi, Enrico Maria, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, Virano, Alexandra, Vocciante, Laura, De Caterina, Raffaele, Iacoviello, Licia, Di Castelnuovo, A., Costanzo, S., Antinori, A., Berselli, N., Bl, I, L., Bonaccio, M., Cauda, R., Gialluisi, A., Guaraldi, G., Menicanti, L., Mennuni, M., Mussinelli, R., My, I., Parruti, G., Patti, G., Perlini, S., Santilli, F., Signorelli, C., Stefanini, G. G., Vergori, A., Abete, P., Ageno, W., Agostoni, P., Aiello, L., Al Moghazi, S., Arboretti, R., Aucella, F., Barbieri, G., Barchitta, M., Bartoloni, A., Bonfanti, P., Cacciatore, F., Caiano, L., Carrozzi, L., Cascio, A., Castiglione, G., Cianfrone, S., Ciccullo, A., Cingolani, A., Cipollone, F., Colomba, C., Colombo, C., Cozzi, O., Crisetti, A., Crosta, F., Danzi, G. B., D'Ardes, D., de Gaetano Donati, K., Di Gennaro, F., Di Tano, G., D'Offizi, G., Fusco, F. M., Gentile, I., Graziani, E., Guarnieri, G., Larizza, G., Leone, A., Lio, V., Lucia, M. B., Maccagni, G., Madaro, F., Maitan, S., Mancarella, S., Manuele, R., Mapelli, M., Maragna, R., Marcucci, R., Maresca, G., Marongiu, S., Marotta, C., Marra, L., Mastroianni, F., Mazzitelli, M., Mengozzi, A., Menichetti, F., Meschiari, M., Milic, J., Minutolo, F., Molena, B., Mussini, C., Musso, M., Odone, A., Olivieri, M., Palimodde, A., Pasi, E., Pesavento, R., Petri, F., Pinchera, B., Pivato, C. A., Poletti, V., Ravaglia, C., Rossato, M., Rossi, M., Sabena, A., Salinaro, F., Sangiovanni, V., Sanrocco, C., Scoppettuolo, G., Scorzolini, L., Sgariglia, R., Simeone, P. G., Trecarichi, E. M., Vettor, R., Vianello, A., Vinceti, M., Virano, A., Vocciante, L., De Caterina, R., Iacoviello, L., Blandi, L., Di Castelnuovo, A, Costanzo, S, Antinori, A, Berselli, N, Blandi, L, Bonaccio, M, Cauda, R, Gialluisi, A, Guaraldi, G, Menicanti, L, Mennuni, M, Mussinelli, R, My, I, Parruti, G, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Stefanini, G, Vergori, A, Abete, P, Ageno, W, Agostoni, P, Aiello, L, Al Moghazi, S, Arboretti, R, Aucella, F, Barbieri, G, Barchitta, M, Bartoloni, A, Bonfanti, P, Cacciatore, F, Caiano, L, Carrozzi, L, Cascio, A, Castiglione, G, Cianfrone, S, Ciccullo, A, Cingolani, A, Cipollone, F, Colomba, C, Colombo, C, Cozzi, O, Crisetti, A, Crosta, F, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Tano, G, D'Offizi, G, Fusco, F, Gentile, I, Graziani, E, Guarnieri, G, Larizza, G, Leone, A, Lio, V, Lucia, M, Maccagni, G, Madaro, F, Maitan, S, Mancarella, S, Manuele, R, Mapelli, M, Maragna, R, Marcucci, R, Maresca, G, Marongiu, S, Marotta, C, Marra, L, Mastroianni, F, Mazzitelli, M, Mengozzi, A, Menichetti, F, Meschiari, M, Milic, J, Minutolo, F, Molena, B, Mussini, C, Musso, M, Odone, A, Olivieri, M, Palimodde, A, Pasi, E, Pesavento, R, Petri, F, Pinchera, B, Pivato, C, Poletti, V, Ravaglia, C, Rossato, M, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Scoppettuolo, G, Scorzolini, L, Sgariglia, R, Simeone, P, Trecarichi, E, Vettor, R, Vianello, A, Vinceti, M, Virano, A, Vocciante, L, Iacoviello, L, and De Caterina, R

Subjects
0301 basic medicine, Male, Physiology, Middle Aged, Renin-Angiotensin System, Angiotensin-Converting Enzyme Inhibitors, 030204 cardiovascular system & hematology, ACE-I, ARB, COVID-19, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, mortality, sartans, Severity of Illness Index, Renin-Angiotensin System, 0302 clinical medicine, Risk Factors, 80 and over, Medicine, Hospital Mortality, Sartan, Aged, 80 and over, Incidence (epidemiology), Incidence, Hazard ratio, Angiotensin Receptor Antagonist, Middle Aged, Hospitalization, Antihypertensive Agent, Italy, Meta-analysis, Hypertension, Sartans, Molecular Medicine, Female, Risk assessment, Human, medicine.medical_specialty, Angiotensin converting enzyme inhibitors, Angiotensin receptor blockers, Mortality, Coronavirus disease 2019 (COVID-19), Risk Assessment, Article, COVID−19, 03 medical and health sciences, Angiotensin Receptor Antagonists, Meta-Analysis as Topic, Internal medicine, Severity of illness, Humans, Angiotensin receptor blocker, Antihypertensive Agents, Aged, Pharmacology, business.industry, Risk Factor, Angiotensin-Converting Enzyme Inhibitor, Confidence interval, 030104 developmental biology, COVID-19, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, mortality, sartans, Observational study, Angiotensin converting enzyme inhibitor, business
Abstract

Objective The hypothesis that been set forward that use of Renin Angiotensin Aldosterone System (RAAS) inhibitors is associated with COVID−19 severity. We set-up a multicenter Italian collaboration (CORIST Project, ClinicalTrials.gov ID: NCT04318418 ) to retrospectively investigate the relationship between RAAS inhibitors and COVID−19 in-hospital mortality. We also carried out an updated meta-analysis on the relevant studies. Methods We analyzed 4069 unselected patients with laboratory-confirmed SARS-CoV-2 infection and hospitalized in 34 clinical centers in Italy from February 19, 2020 to May 23, 2020. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received angiotensin-converting–enzyme inhibitors (ACE I) or angiotensin-receptor blockers (ARB) with patients who did not. Articles for the meta-analysis were retrieved until July 13th, 2020 by searching in web-based libraries, and data were combined using the general variance-based method. Results Out of 4069 COVID−19 patients, 13.5% and 13.3% received ACE-I or ARB, respectively. Use of neither ACE-I nor ARB was associated with mortality (multivariable hazard ratio (HR) adjusted also for COVID−19 treatments: 0.96, 95% confidence interval 0.77–1.20 and HR = 0.89, 0.67–1.19 for ACE-I and ARB, respectively). Findings were similar restricting the analysis to hypertensive (N = 2057) patients (HR = 1.00, 0.78–1.26 and HR = 0.88, 0.65–1.20) or when ACE-I or ARB were considered as a single group. Results from the meta-analysis (19 studies, 29,057 COVID−19 adult patients, 9700 with hypertension) confirmed the absence of association. Conclusions In this observational study and meta-analysis of the literature, ACE-I or ARB use was not associated with severity or in-hospital mortality in COVID−19 patients.

Published
2020

45. Diagnostic performance of deep learning algorithm for analysis of computed tomography myocardial perfusion

Author

Giuseppe Muscogiuri, Mattia Chiesa, Andrea Baggiano, Pierino Spadafora, Rossella De Santis, Marco Guglielmo, Stefano Scafuri, Laura Fusini, Saima Mushtaq, Edoardo Conte, Andrea Annoni, Alberto Formenti, Maria Elisabetta Mancini, Francesca Ricci, Francesco Paolo Ariano, Luigi Spiritigliozzi, Mario Babbaro, Rocco Mollace, Riccardo Maragna, Carlo Maria Giacari, Daniele Andreini, Andrea Igoren Guaricci, Gualtiero I. Colombo, Mark G. Rabbat, Mauro Pepi, Francesco Sardanelli, Gianluca Pontone, Muscogiuri, G, Chiesa, M, Baggiano, A, Spadafora, P, De Santis, R, Guglielmo, M, Scafuri, S, Fusini, L, Mushtaq, S, Conte, E, Annoni, A, Formenti, A, Mancini, M, Ricci, F, Ariano, F, Spiritigliozzi, L, Babbaro, M, Mollace, R, Maragna, R, Giacari, C, Andreini, D, Guaricci, A, Colombo, G, Rabbat, M, Pepi, M, Sardanelli, F, and Pontone, G

Subjects
Myocardial ischemia, Computed Tomography Angiography, Coronary Stenosis, Myocardial Perfusion Imaging, Settore MED/11 - Malattie dell'Apparato Cardiovascolare, Convolutional neural network, Deep learning, General Medicine, Coronary Angiography, Coronary artery disease, Fractional Flow Reserve, Myocardial, Perfusion, Predictive Value of Tests, Humans, Coronary computed tomography angiography, Myocardial CT perfusion, Radiology, Nuclear Medicine and imaging
Abstract

Purpose: Artificial intelligence could play a key role in cardiac imaging analysis. To evaluate the diagnostic accuracy of a deep learning (DL) algorithm predicting hemodynamically significant coronary artery disease (CAD) by using a rest dataset of myocardial computed tomography perfusion (CTP) as compared to invasive evaluation. Methods: One hundred and twelve consecutive symptomatic patients scheduled for clinically indicated invasive coronary angiography (ICA) underwent CCTA plus static stress CTP and ICA with invasive fractional flow reserve (FFR) for stenoses ranging between 30% and 80%. Subsequently, a DL algorithm for the prediction of significant CAD by using the rest dataset (CTP-DLrest) and stress dataset (CTP-DLstress) was developed. The diagnostic accuracy for identification of significant CAD using CCTA, CCTA+CTPStress, CCTA+CTP-DLrest, and CCTA+CTP-DLstress were measured and compared. The time of analysis for CTPStress, CTP-DLrest and CTP-DLStress were recorded. Results: Patient-specific sensitivity, specificity, NPV, PPV, accuracy and area under the curve (AUC) of CCTA alone and CCTA+CTPStress were 100%, 33%, 100%, 54%, 63%, 67% and 86%, 89%, 89%, 86%, 88%, 87%, respectively. Patient-specific sensitivity, specificity, NPV, PPV, accuracy and AUC of CCTA+DLrest and CCTA+DLstress were 100%, 72%, 100%, 74%, 84%, 96% and 93%, 83%, 94%, 81%,88%,98%, respectively. All CCTA+CTPStress, CCTA+CTP-DLRest and CCTA+CTP-DLStress significantly improved detection of hemodynamically significant CAD (pConclusion: Evaluation of myocardial ischemia using a DL approach on rest CTP datasets is feasible and accurate. This approach may be a useful gatekeeper prior to CTPStress.

Published
2022
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46. Value of 3D echocardiography in the diagnosis of arrhythmogenic right ventricular cardiomyopathy

Author

Karima Addetia, Andrea Mazzanti, Riccardo Maragna, Lorenzo Monti, Megan Yamat, Deni Kukavica, Eleonora Pagan, Kanako Kishiki, Aldo Prado, Maira Marino, Vincenzo Bagnardi, Silvia Priori, Roberto M Lang, Addetia, K, Mazzanti, A, Maragna, R, Monti, L, Yamat, M, Kukavica, D, Pagan, E, Kishiki, K, Prado, A, Marino, M, Bagnardi, V, Priori, S, and Lang, R

Subjects
arrhythmogenic right ventricular cardiomyopathy, Task Force Criteria for ARVC, three-dimensional echocardiography, echocardiography, Radiology, Nuclear Medicine and imaging, General Medicine, Cardiology and Cardiovascular Medicine, cardiovascular MRI
Abstract

Aims The 2010 Task Force Criteria (TFC) require that both right ventricular (RV) regional wall-motion abnormalities (WMA) and specific RV size cut-offs be met in order to fulfil one of the major criterion for arrhythmogenic right ventricular cardiomyopathy (ARVC) diagnosis. Currently, 2D echocardiography (2DE) and cardiovascular magnetic resonance imaging (cMRI) are used to determine if these criteria are met. Little is known about the diagnostic value of 3D echocardiography (3DE) in ARVC. The aim of this study was to determine whether a combination of 2DE-3DE is non-inferior to the currently used 2DE-cMRI combination in the diagnosis of patients with ARVC. Methods and results Thirty-nine individuals (47±15 years) with suspected ARVC underwent evaluation of the RV with cMRI, 2DE, and 3DE. 3DE and cMRI were independently used to obtain RV volumes, ejection fraction (EF) and determine the presence of segmental RV WMA. Studies were blindly classified as meeting criteria for ARVC in accordance with the 2010 TFC. Kappa statistics were used to test the concordance between 2DE–cMRI and 2DE–3DE approaches. Using the 2DE–cMRI approach, 3/39 were not affected, 5/39 possible, 8/39 borderline, and 23/39 definite ARVC. The proposed 2DE–3DE approach yielded 5/39 not affected, 7/39 possible, 8/39 borderline, and 19/39 definite diagnoses. The two approaches were highly concordant (k = 0.71; 95% confidence interval: 0.44–0.84). Although 3DE underestimated RV volumes in comparison with cMRI, interfering, in some instances with the fulfilment of a major criterion, it was able to identify more RV WMA (28/39) than 2DE (11/39), with a detection-rate comparable to cMRI (33/39) highlighting a unique advantage. Conclusion The combination of 2DE–3DE for ARVC diagnosis is comparable to the conventional 2DE–cMRI approach. 3DE should be performed in all suspected ARVC patients to aide in the detection of WMA.

Published
2023

47. Gene-Specific Therapy With Mexiletine Reduces Arrhythmic Events in Patients With Long QT Syndrome Type 3

Author

Paola Baiardi, Riccardo Maragna, Andrea Mazzanti, Susan P. Etheridge, Valeria Novelli, Mirella Memmi, Nicola Monteforte, Raffaella Bloise, Vincenzo Bagnardi, Silvia G. Priori, Alessandro Faragli, Carlo Napolitano, Mazzanti, A, Maragna, R, Faragli, A, Monteforte, N, Bloise, R, Memmi, M, Novelli, V, Baiardi, P, Bagnardi, V, Etheridge, S, Napolitano, C, and Priori, S

Subjects
0301 basic medicine, Male, Administration, Oral, LQTS, long QT syndrome, 030204 cardiovascular system & hematology, Sudden cardiac death, Electrocardiography, 0302 clinical medicine, Retrospective Studie, Heart Rate, Medicine, Child, SCN5A, Original Investigation, medicine.diagnostic_test, Medicine (all), Long QT Syndrome, Treatment Outcome, Anesthesia, Cardiology, beta-blocker, Female, Cardiology and Cardiovascular Medicine, Human, medicine.drug, sodium channel, Adult, medicine.medical_specialty, Adolescent, medicine.drug_class, Long QT syndrome, Mexiletine, QT interval, sudden cardiac death, Follow-Up Studie, Young Adult, 03 medical and health sciences, Internal medicine, Heart rate, Humans, Beta blocker, business.industry, LQT3, long QT syndrome type 3, Retrospective cohort study, Genetic Therapy, medicine.disease, CI, confidence interval, 030104 developmental biology, Voltage-Gated Sodium Channel Blocker, ECG, electrocardiogram, mutation, business
Abstract

Background Long QT syndrome type 3 (LQT3) is a lethal disease caused by gain-of-function mutations in the SCN5A gene, coding for the alpha-subunit of the sodium channel NaV1.5. Mexiletine is used to block late sodium current and to shorten QT interval in LQT3 patients. Objectives The aim of this study was to determine whether mexiletine prevents arrhythmic events (arrhythmic syncope, aborted cardiac arrest, or sudden cardiac death) in LQT3 patients. Methods The endpoint of this retrospective cohort study, which studied consecutive LQT3 patients who were referred to our center and treated with mexiletine, was to evaluate the antiarrhythmic efficacy of mexiletine by comparing the number of arrhythmic events per patient and the annual rate of arrhythmic events during observation periods of equal duration before and after the beginning of therapy with mexiletine. Results The study population comprised 34 LQT3 patients, 19 (56%) of whom were male. The median age at beginning of treatment with mexiletine was 22 years, and median QTc interval before therapy 509 ms. The median duration of oral mexiletine therapy was 36 months, at an average daily dose of 8 ± 0.5 mg/kg. Mexiletine significantly shortened QTc (by 63 ± 6 ms; p < 0.0001) and reduced the percentage of patients with arrhythmic events (from 22% to 3%; p = 0.031), the mean number of arrhythmic events per patient (from 0.43 ± 0.17 to 0.03 ± 0.03; p = 0.027), and the annual rate of arrhythmic events (from 10.3% to 0.7%; p = 0.0097). Conclusions Besides shortening QTc interval, mexiletine caused a major reduction of life-threatening arrhythmic events in LQT3 patients, thus representing an efficacious therapeutic strategy.

Published
2016
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48. Interplay Between Genetic Substrate, QTc Duration, and Arrhythmia Risk in Patients With Long QT Syndrome

Author

Nicola Monteforte, Mirella Memmi, Raffaella Bloise, Alberto Malovini, Carlo Napolitano, Vincenzo Bagnardi, L. Braghieri, Silvia G. Priori, Massimo Morini, Gaetano Vacanti, Eleonora Pagan, Andrea Mazzanti, Patrick Gambelli, Luciana Sacilotto, Lorenzo Monserrat, Martín Ortiz, Riccardo Maragna, Maira Marino, Riccardo Bellazzi, Ministero della Salute (Italia), Mazzanti, A, Maragna, R, Vacanti, G, Monteforte, N, Bloise, R, Marino, M, Braghieri, L, Gambelli, P, Memmi, M, Pagan, E, Morini, M, Malovini, A, Ortiz, M, Sacilotto, L, Bellazzi, R, Monserrat, L, Napolitano, C, Bagnardi, V, Priori, S, and Italian Ministry of Health

Subjects
Male, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Genotype, Long QT syndrome, 030204 cardiovascular system & hematology, QT interval, Risk Assessment, sudden cardiac death, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Nadolol, Internal medicine, medicine, Humans, 030212 general & internal medicine, cardiovascular diseases, Proportional hazards model, business.industry, life-threatening arrhythmic event, Hazard ratio, Heart, medicine.disease, inherited arrhythmia, Confidence interval, Long QT Syndrome, beta-blocker, Cardiology, Female, genetic, Cardiology and Cardiovascular Medicine, Risk assessment, business, medicine.drug
Abstract

Long QT syndrome (LQTS) is a common inheritable arrhythmogenic disorder, often secondary to mutations in the KCNQ1, KCNH2, and SCN5A genes. The disease is characterized by a prolonged ventricular repolarization (QTc interval) that confers susceptibility to life-threatening arrhythmic events (LAEs). This study sought to create an evidence-based risk stratification scheme to personalize the quantification of the arrhythmic risk in patients with LQTS. Data from 1,710 patients with LQTS followed up for a median of 7.1 years (interquartile range [IQR]: 2.7 to 13.4 years) were analyzed to estimate the 5-year risk of LAEs based on QTc duration and genotype and to assess the antiarrhythmic efficacy of beta-blockers. The relationship between QTc duration and risk of events was investigated by comparison of linear and cubic spline models, and the linear model provided the best fit. The 5-year risk of LAEs while patients were off therapy was then calculated in a multivariable Cox model with QTc and genotype considered as independent factors. The estimated risk of LAEs increased by 15% for every 10-ms increment of QTc duration for all genotypes. Intergenotype comparison showed that the risk for patients with LQT2 and LQT3 increased by 130% and 157% at any QTc duration versus patients with LQT1. Analysis of response to beta-blockers showed that only nadolol reduced the arrhythmic risk in all genotypes significantly compared with no therapy (hazard ratio: 0.38; 95% confidence interval: 0.15 to 0.93; p = 0.03). The study provides an estimator of risk of LAEs in LQTS that allows a granular estimate of 5-year arrhythmic risk and demonstrate the superiority of nadolol in reducing the risk of LAEs in LQTS. This work was supported by the Ricerca Corrente funding scheme of the Italian Ministry of Health. Dr. Ortiz has received personal fees from Health in Code, SL. Dr. Monserrat is a shareholder in Health in Code, SL. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Sí

Published
2018

49. Hydroquinidine Prevents Life-Threatening Arrhythmic Events in Patients With Short QT Syndrome

Author

Silvia G. Priori, Riccardo Bellazzi, Riccardo Maragna, Gaetano Vacanti, Andrea Mazzanti, Valentina Tibollo, Katherine Underwood, Carlo Napolitano, Maira Marino, Anna Kostopoulou, Nicola Monteforte, Eleonora Pagan, Raffaella Bloise, Vincenzo Bagnardi, Italian Ministry of Health, Mazzanti, A, Maragna, R, Vacanti, G, Kostopoulou, A, Marino, M, Monteforte, N, Bloise, R, Underwood, K, Tibollo, V, Pagan, E, Napolitano, C, Bellazzi, R, Bagnardi, V, Priori, S, and Ministero della Salute (Italia)

Subjects
0301 basic medicine, Adult, Male, medicine.medical_specialty, Adolescent, 030204 cardiovascular system & hematology, arrhythmia, QT interval, sudden cardiac death, Follow-Up Studie, Sudden cardiac death, 03 medical and health sciences, Electrocardiography, Young Adult, 0302 clinical medicine, Heart Conduction System, Heart Rate, Internal medicine, Heart rate, medicine, Humans, Survival rate, short QT syndrome, drug repurposing, medicine.diagnostic_test, business.industry, Incidence, Short QT syndrome, Arrhythmias, Cardiac, medicine.disease, Quinidine, Survival Rate, 030104 developmental biology, Death, Sudden, Cardiac, hydroquinidine, Italy, Anti-Arrhythmia Agent, Ventricular fibrillation, Ventricular Fibrillation, Cardiology, Female, Electrical conduction system of the heart, Cardiology and Cardiovascular Medicine, business, Anti-Arrhythmia Agents, Human, Follow-Up Studies
Abstract

Short QT syndrome (SQTS) is a rare and life-threatening arrhythmogenic syndrome characterized by abbreviated repolarization. Hydroquinidine (HQ) prolongs the QT interval in SQTS patients, although whether it reduces cardiac events is currently unknown. This study investigated whether long-term treatment with HQ reduces the occurrence of life-threatening arrhythmic events (LAE) (cardiac arrest or sudden cardiac death) in SQTS patients. In this cohort study on consecutive SQTS patients, 2 analyses were performed: 1) a matched-period analysis for the occurrence of LAE in 17 SQTS patients who received long-term HQ; and 2) a comparison of the annual incidence of LAE off- and on-HQ in 16 SQTS patients who survived a cardiac arrest. A total of 17 patients (82% male, age 29 ± 3 years, QTc before treatment 331 ± 3 ms) received HQ therapy (584 ± 53 mg/day). Therapy was stopped in 2 cases (12%) due to gastrointestinal intolerance, and 15 patients continued treatment for 6 ± 1 year. QTc prolongation was observed in all patients (by 60 ± 6 ms; p < 0.001). We compared the occurrence of LAE during 6 ± 1 years before and after HQ, observing that patients on HQ experienced a reduction in both the rate of LAE from 40% to 0% (p = 0.03) and the number of LAE per patient from 0.73 ± 0.3 to 0 (p = 0.026). Furthermore, the annual rate of LAE in the 16 patients with a previous cardiac arrest dropped from 12% before HQ to 0 on therapy (p = 0.028). We demonstrated for the first time that treatment with HQ was associated with a lower incidence of LAE in SQTS patients. These data point to the importance that quinidine, that in several countries has been removed from the market, remains available worldwide for patients with SQTS. In the present study, therapy with HQ has been proven to be safe, with a relatively low rate of side effects. This work was supported by the Ricerca Corrente Funding scheme of the Italian Ministry of Health. Dr. Bellazzi is a shareholder of Biomeris; and is a stakeholder of Engenome. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Pedro Brugada, MD, served as Guest Editor for this paper. Sí

Published
2017

50. Role of advanced CMR features in identifying a positive genotype of hypertrophic cardiomyopathy.

Author

Mushtaq S, Chiesa M, Novelli V, Sommariva E, Biondi ML, Manzoni M, Florio A, Lampus ML, Avallone C, Zocchi C, Ianniruberto M, Zannoni J, Nudi A, Arcudi A, Annoni A, Baggiano A, Berna G, Carerj ML, Cannata F, Celeste F, Del Torto A, Fazzari F, Formenti A, Frappampina A, Fusini L, Ali SG, Gripari P, Pizzamiglio F, Ribatti V, Junod D, Maltagliati A, Mancini ME, Mantegazza V, Maragna R, Marchetti F, Muratori M, Sbordone FP, Tassetti L, Volpe A, Saba L, Autore C, Olivotto I, Guaricci AI, Andreini D, and Pontone G

Subjects
Humans, Male, Female, Middle Aged, Adult, Cardiomyopathy, Hypertrophic genetics, Cardiomyopathy, Hypertrophic diagnostic imaging, Genotype, Magnetic Resonance Imaging, Cine methods
Abstract

Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. Cardiac magnetic resonance (CMR) imaging has emerged as a powerful tool for the non-invasive assessment of HCM. CMR can accurately quantify the extent and distribution of hypertrophy, assess the presence and severity of myocardial fibrosis, and detect associated abnormalities. We will study basic and advanced features of CMR in 2 groups of HCM patients with negative and positive genotype, respectively., Materials and Methods: The study population consisted in consecutive HCM patients referred to Centro Cardiologico Monzino who performed both CMR and genetic testing. Clinical CMR images were acquired at 1.5 T Discovery MR450 scanner (GE Healthcare, Milwaukee, Wisconsin)) using standardized protocols T1 mapping, T2 mapping and late gadolinium enhancement (LGE). Population was divided in 2 groups: group 1 with HCM patients with a negative genotype and group 2 with a positive genotype., Results: The analytic population consisted of 110 patients: 75 in group 1 and 35 patients in group 2. At CMR evaluation, patients with a positive genotype had higher LV mass (136 vs. 116 g, p = 0.02), LV thickness (17.5 vs. 16.9 mm), right ventricle ejection fraction (63 % vs. 58 %, p = 0.002). Regarding the LGE patients with positive genotype have a higher absolute (33.8 vs 16.7 g, p = 0.0003) and relative LGE mass (31.6 % vs 14.6 %, p = 0.0007). On a segmental analysis all the septum (segments 2, 8, 9, and 14) had a significantly increased native T1 compared to others segments. ECV in the mid antero and infero-septum (segments 8 and 9) have lower values in positive genotype HCM. Interestingly the mean T2 was lower in positive genotype HCM as compared to negative genotype HCM (50,1 ms vs 52,4)., Conclusions: Our paper identifies the mid septum (segments 8 and 9) as a key to diagnose a positive genotype HCM., Competing Interests: Declaration of competing interest The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Published
2024
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