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3. Italian guidelines for the management of adult individuals with overweight and obesity and metabolic comorbidities that are resistant to behavioral treatment

Author

Chianelli, M., Busetto, L., Vettor, R., Annibale, B., Paoletta, A., Papini, E., Albanese, A., Carabotti, M., Casarotto, D., De Pergola, G., Disoteo, O. E., Grandone, I., Medea, G., Nisoli, E., Raffaelli, M., Schiff, S., Vignati, F., Cinquini, M., Gonzalez-Lorenzo, M., Fittipaldo, V. A., Minozzi, S., Monteforte, M., Tralongo, A. C., Novizio, R., Persichetti, A., Samperi, I., Scoppola, A., Borretta, G., Carruba, M., Carbonelli, M. G., De Luca, M., Frontoni, S., Corradini, S. G., Muratori, F., and Attanasio, R.

Published
2024
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6. Insulin Stimulates IL-23 Expression in Human Adipocytes: A Possible Explanation for the Higher Prevalence of Psoriasis in Obesity

Author

Di Vincenzo A, Granzotto M, Crescenzi M, Costa C, Piaserico S, Vindigni V, Vettor R, and Rossato M

Subjects
adipocyte, human, il-23, insulin, obesity, psoriasis, Specialties of internal medicine, RC581-951
Abstract

Angelo Di Vincenzo,1 Marnie Granzotto,1 Marika Crescenzi,1 Camilla Costa,1 Stefano Piaserico,2 Vincenzo Vindigni,3 Roberto Vettor,1 Marco Rossato1 1Department of Medicine – DIMED, Clinica Medica 3, University - Hospital of Padova, Padova, Italy; 2Department of Medicine - DIMED, Section of Dermatology, University - Hospital of Padova, Padova, Italy; 3Department of Neurosciences, Clinic of Plastic Reconstructive and Aesthetic Surgery, University – Hospital of Padova, Padova, ItalyCorrespondence: Marco Rossato, Department of Medicine – DIMED, Clinica Medica 3, University Hospital of Padova, Via Giustiniani 2, Padova, 35128, Italy, Tel +39 49 8218746, Fax +39 49 8213332, Email marco.rossato@unipd.itPurpose: Psoriasis is a chronic systemic inflammatory disease involving the production of many pro-inflammatory cytokines derived from immune cells and interacting with different tissues leading to the typical skin lesions. Psoriasis shows a higher prevalence and a worse progression in obese than in lean subjects. The IL-23/IL-17 immune axis has a pivotal role in the pathogenesis of psoriasis and anti-IL-23 monoclonal antibodies are highly effective in its treatment. Since obesity in frequently associated with elevated insulin plasma levels, we have investigated the ability of in vitro differentiated human adipocytes to produce IL-23 at basal conditions and after insulin stimulation.Material and Methods: In vitro differentiated human adipocytes were incubated in the absence and presence of different insulin concentrations and the expression of IL-23 was analyzed by real-time PCR and Western blotting.Results: The results of this study show that in vitro differentiated human adipocytes spontaneously express IL-23 mRNA and protein being stimulated by insulin in a dose-dependent manner. The stimulatory effects of insulin on IL-23 expression were specific since it did not stimulate the expression of other well-known cytokines involved in psoriasis pathogenesis such as Il-22 nor LL-37. Furthermore, lipopolysaccharide did not stimulate IL-23 expression in human adipocytes, thus highlightening the specific effects of insulin in the stimulation of IL-23 expression in human adipocytes.Conclusion: Here we show that human adipocytes spontaneously express IL-23 and that insulin stimulates IL-23 production by these cells in a specific manner as other stimuli, known to be involved in psoriasis pathophysiology, are ineffective. These observations could explain the association between psoriasis and obesity, a condition frequently characterized by a state of insulin hypersecretion.Keywords: adipocyte, human, IL-23, insulin, obesity, psoriasis

Published
2023

18. Very-low-calorie ketogenic diet (VLCKD) in the management of metabolic diseases: systematic review and consensus statement from the Italian Society of Endocrinology (SIE)

Author

Caprio, M., Infante, M., Moriconi, E., Armani, A., Fabbri, A., Mantovani, G., Mariani, S., Lubrano, C., Poggiogalle, E., Migliaccio, S., Donini, L. M., Basciani, S., Cignarelli, A., Conte, E., Ceccarini, G., Bogazzi, F., Cimino, L., Condorelli, R. A., La Vignera, S., Calogero, A. E., Gambineri, A., Vignozzi, L., Prodam, F., Aimaretti, G., Linsalata, G., Buralli, S., Monzani, F., Aversa, A., Vettor, R., Santini, F., Vitti, P., Gnessi, L., Pagotto, U., Giorgino, F., Colao, A., and Lenzi, A.

Published
2019
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22. Performance of non-invasive respiratory function indices in predicting clinical outcomes in patients hospitalized for COVID-19 pneumonia in medical and sub-intensive wards: a retrospective cohort study

Author

Cattazzo, F, Inglese, F, Dalbeni, A, Piano, S, Pengo, M, Montagnana, M, Dell'Atti, D, Soliani, F, Cascella, A, Vicini, S, Gambino, C, Minuz, P, Vettor, R, Parati, G, Angeli, P, Fava, C, Cattazzo F., Inglese F., Dalbeni A., Piano S., Pengo M., Montagnana M., Dell'Atti D., Soliani F., Cascella A., Vicini S., Gambino C., Minuz P., Vettor R., Parati G., Angeli P., Fava C., Cattazzo, F, Inglese, F, Dalbeni, A, Piano, S, Pengo, M, Montagnana, M, Dell'Atti, D, Soliani, F, Cascella, A, Vicini, S, Gambino, C, Minuz, P, Vettor, R, Parati, G, Angeli, P, Fava, C, Cattazzo F., Inglese F., Dalbeni A., Piano S., Pengo M., Montagnana M., Dell'Atti D., Soliani F., Cascella A., Vicini S., Gambino C., Minuz P., Vettor R., Parati G., Angeli P., and Fava C.

Abstract

Coronavirus disease 2019 (COVID-19) is a newly recognized infectious disease which can lead to acute respiratory distress syndrome requiring ventilatory support and intensive care unit admission. The aim of our study is to evaluate the performance of two non-invasive respiratory function indices (the ROX index and the SatO2/FiO2 ratio), as compared to the traditional PaO2/FiO2 ratio, in predicting a clinically relevant composite outcome (death or intubation) in hospitalized patients for COVID-19 pneumonia. Four hospital centers in Northern Italy conducted an observational retrospective cohort study during the first wave of COVID-19 pandemic. Four hundred and fifty-six patients with COVID-19 pneumonia admitted to medical or sub-intensive wards were enrolled. Clinical, laboratory, and respiratory parameters, for the calculation of different indices, were measured at hospital admission. In medical wards (Verona and Padua) the PaO2/FiO2 ratio, ROX index and SatO2/FiO2 ratio were able to predict intubation or death with good accuracy (AUROC for the PaO2/FiO2 ratio, ROX index and SatO2/FiO2 ratio of 75%, 75% and 74%, respectively). Regarding sub-intensive wards (Milan and Mantua), none of the three respiratory function indices was significantly associated with the composite outcome. In patients admitted to medical wards for COVID-19 pneumonia, the ROX index and the SatO2/FiO2 ratio demonstrated not only good performance in predicting intubation or death, but their accuracy was comparable to that of the PaO2/FiO2 ratio. In this setting, where repeated arterial blood gas tests are not always feasible, they could be considered a reliable alternative to the invasive PaO2/FiO2 ratio.

Published
2022

23. The CCAAT/Enhancer-Binding Protein beta - SerpinB3 axis inhibition as a novel strategy for Non-Alcoholic Steatohepatitis treatment

Author

Martini, A., primary, Villano, G., additional, Novo, E., additional, Turato, C., additional, Quarta, S., additional, Ruvoletto, M., additional, Biasiolo, A., additional, Protopapa, F., additional, Chinellato, M., additional, Trevellin, E., additional, Granzotto, M., additional, Cannito, S., additional, Cendron, L., additional, De Siervi, S., additional, Guido, M., additional, Parola, M., additional, Vettor, R., additional, and Pontisso, P., additional

Published
2023
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25. Management of Hypothyroidism in Internal Medicine: Patient Profile and Effects of an Educational Programme in the Cluster-Randomized FADOI TIAMO Study

Author

Brancato, D., Biondi, B., Attardo, T. M., Fierro, A., Nizzoli, M., Vettor, R., Monaco, E., Romano, R., Ariete, V., Usai, C., Zagarrì, E., Campanini, M., Brancato, D, Biondi, B, Attardo, Tm, Fierro, A, Nizzoli, M, Vettor, R, Monaco, E, Romano, R, Ariete, V, Usai, C, Zagarrì, E, and Campanini, M

Subjects
Aged, 80 and over, Hospitalization, Male, Hypothyroidism, hospitalized patients , levothyroxine, Thyroxine, Hypothyroidism, Italy, Endocrinology, Diabetes and Metabolism, Humans, Female, Middle Aged, Aged, Retrospective Studies
Abstract

Background and aimsThere is still limited knowledge regarding the clinical profile and appropriateness of treatment in patients with hypothyroidism hospitalized in Internal Medicine (IM) Departments in Italy. The aim of this study is to evaluate: 1) the characteristics of patients and possible deviations from national and international clinical practice recommendations (CPRs) in evidence-based guidelines (EBGs); 2) the improvement of patient management by means of a standardized educational programme (EP).MethodsA nationwide multicentre study, comprising two replications of a retrospective survey (phases 1 and 3) with an intervening EP (phase 2) in half of the centres and no EP in the other half, was conducted. The EP was based on outreach visits. Centres were assigned to the two arms of the study, labelled the training group (TG) and control group (CG) respectively, by cluster randomization. Four EBGs and 39 CPRs provided the basis on which 22 treatment management indicators were identified (7 referring to the time of hospital admission, 15 to post-admission).ResultsThe 21 participating centres recruited 587 hospitalized patients with hypothyroidism, 421 of which were females (71.7%, mean age 74.1 + 14.4 yrs): 318 in phase 1 and 269 in phase 3. The cause of hypothyroidism was unknown in 282 patients (48%). Evaluation at the time of admission identified satisfactory adherence to CPRs (>50%) for 63.6% of the indicators. In the phase 3, TG centres showed significant improvement vs CG in 4 of the 15 post-admission indicators, while 1 out of 15 was significantly worse.ConclusionsThe EP based on outreach visits significantly improved some indicators in the management of patients with hypothyroidism, with specific reference to appropriateness of TSH dosage and levothyroxine (LT4) treatment modality.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT05314790.

Published
2022

27. The accreditation system of Italian medical residency programs: fostering quality and sustainability of the National Health Service

Author

Mazzucco, W., Silenzi, A., Gray, M., Vettor, R., Mazzucco W., Silenzi A., Gray M., and Vettor R.

Subjects
continuous quality improvement, Continuous quality improve-ment, sustainability in healthcare, Internship and Residency, National Health System, standards and requirements, Settore MED/42 - Igiene Generale E Applicata, Post-graduate medical education and training, Quality Improvement, State Medicine, Accreditation, residency programs, Standards and requirement, Italy, Humans, Original Article, Residency program
Abstract

Summary. Background and aim: In June 2017, University and Health Ministries jointly enacted a decree imple-menting a new accreditation system for the Italian post-graduate medical schools (residency programs). We report the innovations introduced through the reform. Methods: Universities were called to submit post-gradu-ate medical school projects to the National Observatory on medical residency programs, the inter-institutional committee responsible for the entire accreditation process, through an interactive web platform. The adherence to minimum standards, requirements and the performances were measured. After this first assessment, universities were asked to provide programs of improvement for critical schools. At the end of the evaluation, residency schools were proposed for a full or a partial accreditation. Results: Of the 1,431 post-graduate medical school projects submitted to the National Observatory by 37 public and 4 private Universities, 672 (47.0%) obtained a full accreditation, 629 (43.9%) a partial accreditation, with a gap to be filled within a two-year period according to a specific improvement programme, while 130 (9.1%) were not accredited. Further, 1,254 out of the 1,301 schools with a full or partial accreditation were activated according to the available public financial resources, excluding those performing the lowest. Annual surveys were in place to investigate the residents’ level of satisfaction concerning the quality of the training programs. The National Observatory further devel-oped an experimental methodology to conduct on-site visits to support quality improvement. Conclusions: This reform can be considered an important initiative to guarantee high standards in the quality of care and to face the challenge of sustainability for the National Health System. (www.actabiomedica.it).

Published
2020

28. Use of low-molecular weight heparin, transfusion and mortality in COVID-19 patients not requiring ventilation

Author

Grandone, E, Tiscia, G, Pesavento, R, De Laurenzo, A, Ceccato, D, Sartori, M, Mirabella, L, Cinnella, G, Mastroianno, M, Dalfino, L, Colaizzo, D, Vettor, R, Intrieri, M, Ostuni, A, Margaglione, M, Alboini, P, Antonioni, A, Aucella, F, Bochicchio, G, Carbonelli, C, Carella, M, Castori, M, Centonze, A, Ciliberti, G, Copetti, M, Corritore, M, De Cosmo, S, D'Aloiso, L, D'Errico, M, de Matthaeis, A, Del Gaudio, A, Di Giorgio, A, Giambra, V, Greco, A, Florio, L, Fontana, A, Inchingolo, V, Inglese, M, Labonia, M, La Marca, A, Latiano, T, Leone, M, Maiello, E, Mangia, A, Marciano, C, Massa, V, Massafra, S, Orciuli, G, Palladino, N, Perna, R, Piscitelli, P, Piemontese, M, Prencipe, M, Raggi, P, Rodriquenz, M, Russo, R, Sancarlo, D, Simeone, A, Trischitta, V, Zarrelli, M, Vaira, P, Vergara, D, Vescovi, A, Grandone E., Tiscia G., Pesavento R., De Laurenzo A., Ceccato D., Sartori M. T., Mirabella L., Cinnella G., Mastroianno M., Dalfino L., Colaizzo D., Vettor R., Intrieri M., Ostuni A., Margaglione M., Alboini P. E., Antonioni A., Aucella F., Bochicchio G. B., Carbonelli C., Carella M., Castori M., Centonze A., Ciliberti G., Copetti M., Corritore M., De Cosmo S., D'Aloiso L., D'Errico M. M., de Matthaeis A., Del Gaudio A., Di Giorgio A., Giambra V., Greco A., Florio L., Fontana A., Inchingolo V., Inglese M., Labonia M., La Marca A., Latiano T., Leone M., Maiello E., Mangia A., Marciano C., Massa V., Massafra S., Orciuli G., Palladino N., Perna R., Piscitelli P., Piemontese M., Prencipe M. A., Raggi P., Rodriquenz M. G., Russo R., Sancarlo D., Simeone A., Trischitta V., Zarrelli M., Vaira P., Vergara D., Vescovi A., Grandone, E, Tiscia, G, Pesavento, R, De Laurenzo, A, Ceccato, D, Sartori, M, Mirabella, L, Cinnella, G, Mastroianno, M, Dalfino, L, Colaizzo, D, Vettor, R, Intrieri, M, Ostuni, A, Margaglione, M, Alboini, P, Antonioni, A, Aucella, F, Bochicchio, G, Carbonelli, C, Carella, M, Castori, M, Centonze, A, Ciliberti, G, Copetti, M, Corritore, M, De Cosmo, S, D'Aloiso, L, D'Errico, M, de Matthaeis, A, Del Gaudio, A, Di Giorgio, A, Giambra, V, Greco, A, Florio, L, Fontana, A, Inchingolo, V, Inglese, M, Labonia, M, La Marca, A, Latiano, T, Leone, M, Maiello, E, Mangia, A, Marciano, C, Massa, V, Massafra, S, Orciuli, G, Palladino, N, Perna, R, Piscitelli, P, Piemontese, M, Prencipe, M, Raggi, P, Rodriquenz, M, Russo, R, Sancarlo, D, Simeone, A, Trischitta, V, Zarrelli, M, Vaira, P, Vergara, D, Vescovi, A, Grandone E., Tiscia G., Pesavento R., De Laurenzo A., Ceccato D., Sartori M. T., Mirabella L., Cinnella G., Mastroianno M., Dalfino L., Colaizzo D., Vettor R., Intrieri M., Ostuni A., Margaglione M., Alboini P. E., Antonioni A., Aucella F., Bochicchio G. B., Carbonelli C., Carella M., Castori M., Centonze A., Ciliberti G., Copetti M., Corritore M., De Cosmo S., D'Aloiso L., D'Errico M. M., de Matthaeis A., Del Gaudio A., Di Giorgio A., Giambra V., Greco A., Florio L., Fontana A., Inchingolo V., Inglese M., Labonia M., La Marca A., Latiano T., Leone M., Maiello E., Mangia A., Marciano C., Massa V., Massafra S., Orciuli G., Palladino N., Perna R., Piscitelli P., Piemontese M., Prencipe M. A., Raggi P., Rodriquenz M. G., Russo R., Sancarlo D., Simeone A., Trischitta V., Zarrelli M., Vaira P., Vergara D., and Vescovi A.

Abstract

It is still debated whether prophylactic doses of low-molecular- weight heparin (LMWH) are always effective in preventing Venous Thromboembolism (VTE) and mortality in COVID-19. Furthermore, there is paucity of data for those patients not requiring ventilation. We explored mortality and the safety/efficacy profile of LMWH in a cohort of Italian patients with COVID-19 who did not undergo ventilation. From the initial cohort of 422 patients, 264 were enrolled. Most (n = 156, 87.7%) received standard LMWH prophylaxis during hospitalization, with no significant difference between medical wards and Intensive Care Unit (ICU). Major or not major but clinically relevant hemorrhages were recorded in 13 (4.9%) patients: twelve in those taking prophylactic LMWH and one in a patient taking oral anticoagulants (p: n.s.). Thirty-nine patients (14.8%) with median age 75 years. were transfused. Hemoglobin (Hb) at admission was significantly lower in transfused patients and Hb at admission inversely correlated with the number of red blood cells units transfused (p < 0.001). In-hospital mortality occurred in 76 (28.8%) patients, 46 (24.3%) of whom admitted to medical wards. Furthermore, Hb levels at admittance were significantly lower in fatalities (g/dl 12.3; IQR 2.4 vs. 13.3; IQR 2.8; Mann–Whitney U-test; p = 0.001). After the exclusion of patients treated by LMWH intermediate or therapeutic doses (n = 32), the logistic regression showed that prophylaxis significantly and independently reduced mortality (OR 0.31, 95% CI 0.13–0.85). Present data show that COVID-19 patients who do not require ventilation benefit from prophylactic doses of LMWH.

Published
2021

30. Clinical factors associated with death in 3044 COVID-19 patients managed in internal medicine wards in Italy: results from the SIMI-COVID-19 study of the Italian Society of Internal Medicine (SIMI)

Author

Corradini E., Ventura P., Ageno W., Cogliati C. B., Muiesan M. L., Girelli D., Pirisi M., Gasbarrini A., Angeli P., Querini P. R., Bosi E., Tresoldi M., Vettor R., Cattaneo M., Piscaglia F., Brucato A. L., Perlini S., Martelletti P., Pontremoli R., Porta M., Minuz P., Olivieri O., Sesti G., Biolo G., Rizzoni D., Serviddio G., Cipollone F., Grassi D., Manfredini R., Moreo G. L., Pietrangelo A., Teatini T., Salvetti M., Crisafulli E., Sainaghi P. P., Zileri Dal Verme L., Piano S., De Lorenzo R., Arcidiacono G., Podda M., Muratori L., Gabiati C., Salinaro F., Luciani M., Barnini C., Morra di Cella S., Dalbeni A., Friso S., Mearelli F., Malerba P., Cavallone F., D'Ardes D., Notargiacomo S., De Giorgi A., Mansi M., Buzzetti E., Ricci A., Martelli F., Corradini E., Ventura P., Ageno W., Cogliati C.B., Muiesan M.L., Girelli D., Pirisi M., Gasbarrini A., Angeli P., Querini P.R., Bosi E., Tresoldi M., Vettor R., Cattaneo M., Piscaglia F., Brucato A.L., Perlini S., Martelletti P., Pontremoli R., Porta M., Minuz P., Olivieri O., Sesti G., Biolo G., Rizzoni D., Serviddio G., Cipollone F., Grassi D., Manfredini R., Moreo G.L., Pietrangelo A., Teatini T., Salvetti M., Crisafulli E., Sainaghi P.P., Zileri Dal Verme L., Piano S., De Lorenzo R., Arcidiacono G., Podda M., Muratori L., Gabiati C., Salinaro F., Luciani M., Barnini C., Morra di Cella S., Dalbeni A., Friso S., Mearelli F., Malerba P., Cavallone F., D'Ardes D., Notargiacomo S., De Giorgi A., Mansi M., Buzzetti E., Ricci A., Martelli F., Corradini, E., Ventura, P., Ageno, W., Cogliati, C. B., Muiesan, M. L., Girelli, D., Pirisi, M., Gasbarrini, A., Angeli, P., Rovere-Querini, P., Bosi, E., Tresoldi, M., Vettor, R., Cattaneo, M., Piscaglia, F., Brucato, A. L., Perlini, S., Martelletti, P., Pontremoli, R., Porta, M., Minuz, P., Olivieri, O., Sesti, G., Biolo, G., Rizzoni, D., Serviddio, G., Cipollone, F., Grassi, D., Manfredini, R., Moreo, G. L., Pietrangelo, A., Teatini, T., Salvetti, M., Crisafulli, E., Sainaghi, P. P., Zileri Dal Verme, L., Piano, S., De Lorenzo, R., Arcidiacono, G., Podda, M., Muratori, L., Gabiati, C., Salinaro, F., Luciani, M., Barnini, C., Morra di Cella, S., Dalbeni, A., Friso, S., Mearelli, F., Malerba, P., Cavallone, F., D'Ardes, D., Notargiacomo, S., De Giorgi, A., Mansi, M., Buzzetti, E., Ricci, A., and Martelli, F.

Subjects
Mortality from COVID-19, Comorbidity, 030204 cardiovascular system & hematology, Cohort Studies, 0302 clinical medicine, 80 and over, Medicine, 030212 general & internal medicine, Hospital Mortality, Internal medicine, Comorbidity, Internal medicine, Mortality from COVID-19, Polypharmacy, SARS-CoV-2, Aged, 80 and over, LS7_9, Mortality rate, Respiration, Middle Aged, Hospitals, Survival Rate, Hospitalization, Italy, Polypharmacy, SARS-CoV-2, Cohort, Artificial, Emergency Medicine, Adult, Aged, COVID-19, Critical Care, Humans, Respiration, Artificial, Internal Medicine, medicine.symptom, Cohort study, medicine.medical_specialty, Settore MED/12 - GASTROENTEROLOGIA, Socio-culturale, 03 medical and health sciences, Intensive care, Survival rate, business.industry, Organ dysfunction, Settore MED/09 - MEDICINA INTERNA, medicine.disease, Im - Original, business
Abstract

During the COVID-19 2020 outbreak, a large body of data has been provided on general management and outcomes of hospitalized COVID-19 patients. Yet, relatively little is known on characteristics and outcome of patients managedin Internal Medicine Units (IMU). To address this gap, the Italian Society of Internal Medicine has conducted a nationwide cohort multicentre study on death outcome in adult COVID-19 patients admitted and managed in IMU. This study assessed 3044 COVID-19 patients at 41 referral hospitals across Italy from February 3rd to May 8th 2020. Demographics, comorbidities, organ dysfunction, treatment, and outcomes including death were assessed. During the study period, 697 patients (22.9%) were transferred to intensive care units, and 351 died in IMU (death rate 14.9%). At admission, factors independently associated with in-hospital mortality were age (OR 2.46, p = 0.000), productive cough (OR 2.04, p = 0.000), pre-existing chronic heart failure (OR 1.58, p = 0.017) and chronic obstructive pulmonary disease (OR 1.17, p = 0.048), the number of comorbidities (OR 1.34, p = 0.000) and polypharmacy (OR 1.20, p = 0.000). Of note, up to 40% of elderly patients did not report fever at admission. Decreasing PaO2/FiO2 ratio at admission was strongly inversely associated with survival. The use of conventional oxygen supplementation increased with the number of pre-existing comorbidities, but it did not associate with better survival in patients with PaO2/FiO2 ratio

Published
2021

31. 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

36. Use of low-molecular weight heparin, transfusion and mortality in COVID-19 patients not requiring ventilation

Author

Grandone, E., Tiscia, G., Pesavento, R., De Laurenzo, A., Ceccato, D., Sartori, M. T., Mirabella, L., Cinnella, G., Mastroianno, M., Dalfino, L., Colaizzo, D., Vettor, R., Intrieri, M., Ostuni, A., Margaglione, M., Alboini, P. E., Antonioni, A., Aucella, F., Bochicchio, G. B., Carbonelli, C., Carella, M., Castori, M., Centonze, A., Ciliberti, G., Copetti, M., Corritore, M., De Cosmo, S., D'Aloiso, L., D'Errico, M. M., de Matthaeis, A., Del Gaudio, A., Di Giorgio, A., Giambra, V., Greco, A., Florio, L., Fontana, A., Inchingolo, V., Inglese, M., Labonia, M., La Marca, A., Latiano, T., Leone, M., Maiello, E., Mangia, A., Marciano, C., Massa, V., Massafra, S., Orciuli, G., Palladino, N., Perna, R., Piscitelli, P., Piemontese, M., Prencipe, M. A., Raggi, P., Rodriquenz, M. G., Russo, R., Sancarlo, D., Simeone, A., Trischitta, V., Zarrelli, M., Vaira, P., Vergara, D., Vescovi, A., Grandone, E, Tiscia, G, Pesavento, R, De Laurenzo, A, Ceccato, D, Sartori, M, Mirabella, L, Cinnella, G, Mastroianno, M, Dalfino, L, Colaizzo, D, Vettor, R, Intrieri, M, Ostuni, A, Margaglione, M, Alboini, P, Antonioni, A, Aucella, F, Bochicchio, G, Carbonelli, C, Carella, M, Castori, M, Centonze, A, Ciliberti, G, Copetti, M, Corritore, M, De Cosmo, S, D'Aloiso, L, D'Errico, M, de Matthaeis, A, Del Gaudio, A, Di Giorgio, A, Giambra, V, Greco, A, Florio, L, Fontana, A, Inchingolo, V, Inglese, M, Labonia, M, La Marca, A, Latiano, T, Leone, M, Maiello, E, Mangia, A, Marciano, C, Massa, V, Massafra, S, Orciuli, G, Palladino, N, Perna, R, Piscitelli, P, Piemontese, M, Prencipe, M, Raggi, P, Rodriquenz, M, Russo, R, Sancarlo, D, Simeone, A, Trischitta, V, Zarrelli, M, Vaira, P, Vergara, D, and Vescovi, A

Subjects
Male, Time Factors, 030204 cardiovascular system & hematology, Logistic regression, law.invention, 0302 clinical medicine, law, Risk Factors, 80 and over, 030212 general & internal medicine, Hospital Mortality, Hematology, Low-Molecular-Weight, COVID-19, Low-molecular-weight heparin, Mortality, Ventilation, Aged, Aged, 80 and over, Anticoagulants, Clinical Decision-Making, Female, Heparin, Low-Molecular-Weight, Hospitalization, Humans, Middle Aged, Protective Factors, Risk Assessment, Thromboembolism, Treatment Outcome, Blood Transfusion, Heparin, Intensive care unit, Cohort, Breathing, Cardiology and Cardiovascular Medicine, medicine.drug, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), medicine.drug_class, Low molecular weight heparin, Article, 03 medical and health sciences, Internal medicine, medicine, low-molecular-weight heparin, mortality, ventilation, aged, aged 80 and over, anticoagulants, clinical decision-making, female, low-molecular-weight, hospital mortality, hospitalization, humans, male, middle aged, protective factors, risk assessment, risk factors, thromboembolism, time factors, treatment outcome, blood transfusion, business.industry, business
Abstract

It is still debated whether prophylactic doses of low-molecular- weight heparin (LMWH) are always effective in preventing Venous Thromboembolism (VTE) and mortality in COVID-19. Furthermore, there is paucity of data for those patients not requiring ventilation. We explored mortality and the safety/efficacy profile of LMWH in a cohort of Italian patients with COVID-19 who did not undergo ventilation. From the initial cohort of 422 patients, 264 were enrolled. Most (n = 156, 87.7%) received standard LMWH prophylaxis during hospitalization, with no significant difference between medical wards and Intensive Care Unit (ICU). Major or not major but clinically relevant hemorrhages were recorded in 13 (4.9%) patients: twelve in those taking prophylactic LMWH and one in a patient taking oral anticoagulants (p: n.s.). Thirty-nine patients (14.8%) with median age 75 years. were transfused. Hemoglobin (Hb) at admission was significantly lower in transfused patients and Hb at admission inversely correlated with the number of red blood cells units transfused (p < 0.001). In-hospital mortality occurred in 76 (28.8%) patients, 46 (24.3%) of whom admitted to medical wards. Furthermore, Hb levels at admittance were significantly lower in fatalities (g/dl 12.3; IQR 2.4 vs. 13.3; IQR 2.8; Mann–Whitney U-test; p = 0.001). After the exclusion of patients treated by LMWH intermediate or therapeutic doses (n = 32), the logistic regression showed that prophylaxis significantly and independently reduced mortality (OR 0.31, 95% CI 0.13–0.85). Present data show that COVID-19 patients who do not require ventilation benefit from prophylactic doses of LMWH.

Published
2021

40. Correction to: Use of low-molecular weight heparin, transfusion and mortality in COVID-19 patients not requiring ventilation

Author

Grandone, E., Tiscia, G., Pesavento, R., De Laurenzo, A., Ceccato, D., Sartori, M. T., Mirabella, L., Cinnella, G., Mastroianno, M., Dalfino, L., Colaizzo, D., Vettor, R., Intrieri, M., Ostuni, A., Margaglione, M., Alboini, P. E., Antonioni, A., Aucella, F., Bochicchio, G. B., Carbonelli, C., Carella, M., Castori, M., Centonze, A., Ciliberti, G., Copetti, M., Corritore, M., De Cosmo, S., D'Aloiso, L., D'Errico, M. M., de Matthaeis, A., Del Gaudio, A., Di Giorgio, A., Giambra, V., Greco, A., Florio, L., Fontana, A., Inchingolo, V., Inglese, M., Labonia, M., La Marca, A., Latiano, T., Leone, M., Maiello, E., Mangia, A., Marciano, C., Massa, V., Massafra, S., Orciulo, G., Palladino, N., Perna, R., Piscitelli, P., Piemontese, M., Prencipe, M. A., Raggi, P., Rodriquenz, M. G., Russo, R., Sancarlo, D., Simeone, A., Trischitta, V., Zarrelli, M., Vaira, P., Vergara, D., and Vescovi, A.

Subjects
Male, 2019-20 coronavirus outbreak, medicine.medical_specialty, Time Factors, Coronavirus disease 2019 (COVID-19), medicine.drug_class, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Clinical Decision-Making, Low molecular weight heparin, Risk Assessment, Risk Factors, Internal medicine, Thromboembolism, medicine, Humans, Blood Transfusion, Hospital Mortality, Aged, Aged, 80 and over, Hematology, business.industry, Correction, Anticoagulants, COVID-19, Heparin, Low-Molecular-Weight, Middle Aged, Protective Factors, CSS COVID-19 Group, Covid-19, research groups, Hospitalization, Treatment Outcome, Emergency medicine, Breathing, Female, Cardiology and Cardiovascular Medicine, business
Abstract

It is still debated whether prophylactic doses of low-molecular- weight heparin (LMWH) are always effective in preventing Venous Thromboembolism (VTE) and mortality in COVID-19. Furthermore, there is paucity of data for those patients not requiring ventilation. We explored mortality and the safety/efficacy profile of LMWH in a cohort of Italian patients with COVID-19 who did not undergo ventilation. From the initial cohort of 422 patients, 264 were enrolled. Most (n = 156, 87.7%) received standard LMWH prophylaxis during hospitalization, with no significant difference between medical wards and Intensive Care Unit (ICU). Major or not major but clinically relevant hemorrhages were recorded in 13 (4.9%) patients: twelve in those taking prophylactic LMWH and one in a patient taking oral anticoagulants (p: n.s.). Thirty-nine patients (14.8%) with median age 75 years. were transfused. Hemoglobin (Hb) at admission was significantly lower in transfused patients and Hb at admission inversely correlated with the number of red blood cells units transfused (p 0.001). In-hospital mortality occurred in 76 (28.8%) patients, 46 (24.3%) of whom admitted to medical wards. Furthermore, Hb levels at admittance were significantly lower in fatalities (g/dl 12.3; IQR 2.4 vs. 13.3; IQR 2.8; Mann-Whitney U-test; p = 0.001). After the exclusion of patients treated by LMWH intermediate or therapeutic doses (n = 32), the logistic regression showed that prophylaxis significantly and independently reduced mortality (OR 0.31, 95% CI 0.13-0.85). Present data show that COVID-19 patients who do not require ventilation benefit from prophylactic doses of LMWH.

Published
2021

41. Correction to: Use of low-molecular weight heparin, transfusion and mortality in COVID-19 patients not requiring ventilation (Journal of Thrombosis and Thrombolysis, (2021), 52, 3, (772-778), 10.1007/s11239-021-02429-z)

Author

Grandone, E., Tiscia, G., Pesavento, R., De Laurenzo, A., Ceccato, D., Sartori, M. T., Mirabella, L., Cinnella, G., Mastroianno, M., Dalfino, L., Colaizzo, D., Vettor, R., Intrieri, M., Ostuni, A., Margaglione, M., Alboini, P. E., Antonioni, A., Aucella, F., Bochicchio, G. B., Carbonelli, C., Carella, M., Castori, M., Centonze, A., Ciliberti, G., Copetti, M., Corritore, M., De Cosmo, S., D'Aloiso, L., D'Errico, M. M., de Matthaeis, A., Del Gaudio, A., Di Giorgio, A., Giambra, V., Greco, A., Florio, L., Fontana, A., Inchingolo, V., Inglese, M., Labonia, M., La Marca, A., Latiano, T., Leone, M., Maiello, E., Mangia, A., Marciano, C., Massa, V., Massafra, S., Orciulo, G., Palladino, N., Perna, R., Piscitelli, P., Piemontese, M., Prencipe, M. A., Raggi, P., Rodriquenz, M. G., Russo, R., Sancarlo, D., Simeone, A., Trischitta, V., Zarrelli, M., Vaira, P., Vergara, D., and Vescovi, A.

Published
2021

42. 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

43. 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

44. 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

45. Effects of insomnia and restless legs syndrome on sleep arterial blood pressure: A systematic review and meta-analysis

Author

Maiolino, G, Bisogni, V, Soranna, D, Pengo, M, Pucci, G, Vettor, R, Fava, C, Colussi, G, Bilo, G, Lombardi, C, Parati, G, Rossi, G, Silvani, A, Colussi, GL, Rossi, GP, Maiolino, G, Bisogni, V, Soranna, D, Pengo, M, Pucci, G, Vettor, R, Fava, C, Colussi, G, Bilo, G, Lombardi, C, Parati, G, Rossi, G, Silvani, A, Colussi, GL, and Rossi, GP

Abstract

Hypertension and blunted blood pressure (BP) dipping during nighttime sleep are associated with increased cardiovascular risk. Chronic insomnia and restless legs syndrome (RLS) may affect the 24-h BP profile. We systematically reviewed the association of insomnia and RLS with BP values during nighttime sleep and the relative BP dipping pattern. We searched relevant articles in any language with selection criteria including enrolment of subjects with insomnia or RLS and with obstructive sleep apnea comorbidity assessment. Of the 872 studies originally retrieved, seven were selected. Four studies enrolled subjects with insomnia. One study relied on sleep diaries to classify nighttime sleep BP, whereas three relied only on clock time. At meta-analysis, subjects with insomnia displayed an attenuated dipping of systolic BP (−2.00%; 95% confidence interval (CI): −3.61 - −0.39%) and diastolic BP (−1.58%; 95% CI: −2.66 ̶ −0.49%) during nighttime sleep compared to controls. Three studies enrolled subjects with RLS. One study relied on polysomnography to classify nighttime sleep BP, whereas two relied only on clock time. Subjects with RLS showed increases in nighttime sleep systolic BP (5.61 mm Hg, 95% CI 0.13̶–11.09 mm Hg) compared to controls. In conclusion, the limited available data suggest that insomnia and RLS are both associated with altered BP control during nighttime sleep. There is need for more clinical studies to confirm these findings, specifically focusing on measurements of BP during objectively defined sleep, on causal roles of leg movements during sleep and alterations in sleep architecture, and on implications for cardiovascular risk. Prospero acknowledgement of number: CRD42020217947.

Published
2021

46. Clinical factors associated with death in 3044 COVID-19 patients managed in internal medicine wards in Italy: results from the SIMI-COVID-19 study of the Italian Society of Internal Medicine (SIMI)

Author

Corradini, E., Ventura, P., Ageno, W., Cogliati, C. B., Muiesan, M. L., Girelli, Davide Nicola, Pirisi, M., Gasbarrini, Antonio, Angeli, P., Querini, P. R., Bosi, E., Tresoldi, M., Vettor, R., Cattaneo, M., Piscaglia, F., Brucato, A. L., Perlini, S., Martelletti, P., Pontremoli, R., Porta, M., Minuz, P., Olivieri, O., Sesti, G., Biolo, G., Rizzoni, D., Serviddio, G., Cipollone, F., Grassi, D., Manfredini, R., Moreo, G. L., Pietrangelo, A., Teatini, T., Salvetti, Maria Cristina, Crisafulli, E., Sainaghi, Pier Paolo, Zileri Dal Verme, Lorenzo, Piano, S., De Lorenzo, R., Arcidiacono, G., Podda, Maria Vittoria, Muratori, L., Gabiati, C., Salinaro, F., Luciani, Massimiliano, Barnini, C., Morra di Cella, S., Dalbeni, A., Friso, S., Mearelli, F., Malerba, P., Cavallone, F., D'Ardes, D., Notargiacomo, S., De Giorgi, A., Mansi, M., Buzzetti, E., Ricci, A., Martelli, Franco, Girelli D., Gasbarrini A. (ORCID:0000-0002-7278-4823), Salvetti M., Sainaghi P. P., Zileri Dal Verme L., Podda M. (ORCID:0000-0002-2779-8417), Luciani M., Martelli F., Corradini, E., Ventura, P., Ageno, W., Cogliati, C. B., Muiesan, M. L., Girelli, Davide Nicola, Pirisi, M., Gasbarrini, Antonio, Angeli, P., Querini, P. R., Bosi, E., Tresoldi, M., Vettor, R., Cattaneo, M., Piscaglia, F., Brucato, A. L., Perlini, S., Martelletti, P., Pontremoli, R., Porta, M., Minuz, P., Olivieri, O., Sesti, G., Biolo, G., Rizzoni, D., Serviddio, G., Cipollone, F., Grassi, D., Manfredini, R., Moreo, G. L., Pietrangelo, A., Teatini, T., Salvetti, Maria Cristina, Crisafulli, E., Sainaghi, Pier Paolo, Zileri Dal Verme, Lorenzo, Piano, S., De Lorenzo, R., Arcidiacono, G., Podda, Maria Vittoria, Muratori, L., Gabiati, C., Salinaro, F., Luciani, Massimiliano, Barnini, C., Morra di Cella, S., Dalbeni, A., Friso, S., Mearelli, F., Malerba, P., Cavallone, F., D'Ardes, D., Notargiacomo, S., De Giorgi, A., Mansi, M., Buzzetti, E., Ricci, A., Martelli, Franco, Girelli D., Gasbarrini A. (ORCID:0000-0002-7278-4823), Salvetti M., Sainaghi P. P., Zileri Dal Verme L., Podda M. (ORCID:0000-0002-2779-8417), Luciani M., and Martelli F.

Abstract

During the COVID-19 2020 outbreak, a large body of data has been provided on general management and outcomes of hospitalized COVID-19 patients. Yet, relatively little is known on characteristics and outcome of patients managed in Internal Medicine Units (IMU). To address this gap, the Italian Society of Internal Medicine has conducted a nationwide cohort multicentre study on death outcome in adult COVID-19 patients admitted and managed in IMU. This study assessed 3044 COVID-19 patients at 41 referral hospitals across Italy from February 3rd to May 8th 2020. Demographics, comorbidities, organ dysfunction, treatment, and outcomes including death were assessed. During the study period, 697 patients (22.9%) were transferred to intensive care units, and 351 died in IMU (death rate 14.9%). At admission, factors independently associated with in-hospital mortality were age (OR 2.46, p = 0.000), productive cough (OR 2.04, p = 0.000), pre-existing chronic heart failure (OR 1.58, p = 0.017) and chronic obstructive pulmonary disease (OR 1.17, p = 0.048), the number of comorbidities (OR 1.34, p = 0.000) and polypharmacy (OR 1.20, p = 0.000). Of note, up to 40% of elderly patients did not report fever at admission. Decreasing PaO2/FiO2 ratio at admission was strongly inversely associated with survival. The use of conventional oxygen supplementation increased with the number of pre-existing comorbidities, but it did not associate with better survival in patients with PaO2/FiO2 ratio < 100. The latter, significantly benefited by the early use of non-invasive mechanical ventilation. Our study identified PaO2/FiO2 ratio at admission and comorbidity as the main alert signs to inform clinical decisions and resource allocation in non-critically ill COVID-19 patients admitted to IMU.

Published
2021

49. Abstract

Author

Andries, L. J., Sys, S. U., Meulemans, A. L., Schuurkes, J. A. J., Vanheel, B., Van de Voorde, J., De Smet, P., Li, J., Van Driessche, W., Flamion, B., Foulon, S., Abramow, M., Calders, P., Eechaute, W., Lacroix, E., Weyne, I., Hoeben, D., Burvenich, C., Fransen, P., Andries, L. J., Van Bedaf, D., Demolder, M., Sys, S. U., Ouedraogo, R., Lebrun, P., Herchuelz, A., Antoine, M. -H., Vandenput, S., Votion, D., Anciaux, N., Duvivier, D. H., Art, T., Lekeux, P., Votion, D., Ghafir, Y., Vandenput, S., Art, T., Lekeux, P., Geurts, M., Hermans, E., Maloteaux, J. -M., Perrad, B., Noel, B., Lagache, F., Bister, J. L., Paquay, R., Bister, J. L., Derycke, G., Vandermeir, M. A., Paquay, R., de Brouwer, S., Porret, C. -A., Stergiopulos, N., Meister, J. -J., Verbeke, M., Van de Voorde, J., Lameire, N., De Clerck, N. M., De Schuytter, J., Tytgato, J., Buyse, G., Eggermont, J., Droogmans, G., Nilius, B., Daenens, P., Salomone, S., Feron, O., Dessy, C., Morel, N., Godfraind, T., Aloisi, A. M., Sacerdote, P., Lodi, L., Carli, G., Carobi, C., Garinei, G., Miniaci, U. C., Scotto, P., Sabatino, M., Sardo, P., Iurato, L., La Grutta, V., Bagni, M. A., Cecchi, G., Cecchini, E., Colomo, F., Garzella, P., Bottinelli, R., Harridge, S. D. H., Canepari, M., Reggiani, C., Reggiani, Saltin, Bambagioni, D., Fanò, G., Menchetti, G,, Danieli-Betto, P., Esposito, A., Betto, R., Megighian, A., Midrio, M., Betto, D. Danieli, Esposito, A., Megighian, A., Midrio, M., Orizio, C., Liberati, D., Locatelli, C., De Grandis, D., Veicsteinas, A., Angoli, D., Delia, D., Wanke, E., Bramucci, M., Miano, A., Quassinti, L., Maccari, E., Murri, O., Amici, D., Cibelli, G., Jüngling, S., Schoch, S., Gerdest, H. H., Thiel, G., Demori, I., Bottazzi, C., Voci, A., Fugassa, E., Barreca, A., Minuto, F., Gallo, G., Fulle, S., Belia, S., Menchetti, G., Cacchio, M., Fanò, G., Gastaldi, G., Laforenza, U., Ferrari, G., Rindi, G., Doni, M. G., Padoin, E., Residori, O., Cesaro, M., Toma, L., Rubini, A., Mutinelli, F, Paulesu, L., Romagnolie, R., Cintorino, M., Pippia, P., Meloni, M. A., Sciola, L., Spano, A., Cogoli-Greuter, M., Cogoli, A., Sardini, A., Mintenig, G. M., Valverde, M. A., Sepùlveda, F. V., Gill, D. R., Hyde, S. C., Higgins, C. F., McNaughton, P. A., Spena, A., Arcuri, M. T., Bonofiglio, S., Chimenti, R., Covello, C., De Cicco, T., Mazzulla, S., Martino, G., Tottene, A., Moretti, A., Pietrobon, D., Baccari, M. C., Calamai, F., Staderini, G., Cova, E., Marelli, R., Sommi, P., Ventura, U., Lombardi, A. M., Fabris, R., Pagano, C., Federspil, G., Vettor, R., Mancinelli, R., Tonali, P., Servidei, S., Romani, R., Tringali, A., Azzena, G. B., Mulè, F., Serio, R., Postorino, A., Pagano, C., Rizzato, M., Granzotto, M., Lombardi, A. M., Fabris, R., Vettor, R., Federspil, G., Sommi, P., Ricci, V., Romano, M., Ivey, K. J., Ventura, U., Vacca, G., Papillo, B., Mary, D. A. S. G., Battaglia, A., Grossini, E., Vacca, G., Papillo, B., Battaglia, A., Grossini, E., Accili, E. A., Redaelli, G., DiFrancesco, D., Antoniotti, S., Distasi, C., Lovisolo, D., Munaron, L., Bertaso, F., Assandri, R., Mazzanti, M., Bianchi, L., Arcangeli, A., Faravelli, L., Becchetti, A., Coronello, M., Mini, E., Francini, F., Olivotto, M., Wanke, E., Bigiani, A., Kim, D. -J., Roper, S. D., Carabelli, V., Lovallo, M., Magnelli, V., Zucker, H., Carbone, E., D’Angelo, E., Rossi, P., De Filippi, G., Taglietti, V., Faravelli, L., Bianchi, L., Arcangeli, A., Francini, F., Olivotto, M., Wanke, E., Francini, F., Bencini, C., Squecco, R., Guatteo, E., Bacci, A., Franceschetti, S., Avanzini, G., Wanke, E., Magnelli, V., Carbone, E., Mazzanti, M., Assandri, R., Ferroni, A., DiFrancesco, D., Navangione, A., Vellani, V., Rispoli, G., Peres, A., Centinaio, E., Giovannardi, S., Russo, G., Marcotti, W., Prigioni, I., Trequattrini, C., Harper, A. A., Petris, A., Franciolini, F., Zaza, A., Micheletti, M., Brioschi, A., Antonutto, G., Capelli, C., Girardis, M., Zamparo, P., di Prampero, P. E., Antonutto, G., Girardis, M., Tuniz, D., di Prampero, P. E., Filippi, G. M., Troiani, D., Grassi, B., Poole, D. C., Richardson, R. S., Knight, D. R., Erickson, B. K., Wagner, P. D., Aimi, B., Stilli, D., Gallo, P., Sgoifo, A., Lagrasta, C., Olivetti, G., Reali, N., Casti, A., Musso, E., Alloatti, G., Penna, C., Gallo, M. P., Levi, R. C., Fenoglio, I., Appendino, G., Gallo, P., Sgoifo, A., Medici, D., Aimi, B., Manghi, M., Stilli, D., Musso, E., Sgoifo, A., Pasini, E., Gallo, P., Aimi, B., Stilli, D., Ceconi, C., Musso, E., Baldissera, F., Cavallari, P., Locatelli, M., Bartesaghi, R., Gessi, T., Benfenati, F., Valtorta, F., Onofri, F., Poo, M., Greengard, P., Biagini, G., Sala, D., Viani§, P., Kozlov, A. V., Zini, I., Bravin, M., Tempia, F., Strata, P., Brescia, G., Di Benedetto, C., Corsi, P., Cangiano, G., Buttiglione, M., Ambrosini, M., Gennarini, G., Casadio, A., Levi, R. C., Montarolo, P. G., Cesare, P., Stoughton, R., McNaughton, P. A., D’Arcangelo, G., Dodt, H. U., Brancati, A., Zieglgänsberger, W., Errico, P., Ferraresi, A., Barmack, N. H., Pettorossi, V. E., Gasparini, S., D’Ambrosio, R., Janigro, D., DiFrancesco, D., Gritti, I., Marintti, M., Calcaterra, R., Freddi, R., Mancia, M., Imeri, I., Bianchi, S., Mancia, M., Lui, F., Gregory, K. M., Blanks, R. H. I., Giolli, R. A., Benassi, C., Corazza, R., Magherini, P. C., Bardoni, R., Belluzzi, O., Mancinelli, R., Manni, E., Azzena, G. B., Tringali, A., Romani, R., Diana, M., Fratta, W., Manzoni, D., Andre, P., Pompeiano, O., Mazzocchio, R., Rossi, A., Melis, F., Kitura, A., Caria, M. A., Asanuma, H., Melone, M, De Biasi, S, Minelli, A, Conti, F, Minelli, A, Karschin, C, DeBiasi, S, Brecha, N C, Conti, F, Monda, M., Amaro, S., Sullo, A., De Luca, B., Monda, M., Amaro, S., Sullo, A., De Luca, B., Pantò, M. R., Cicirata, F., Parenti, R., Serapide, M. F., Parenti, R., Wassef, M., Cicirata, F., Podda, M. V., Solinas, A., Chessa, G., Deriu, F., Mameli, O., Tolu, E., Pompeiano, O., Andre, P., Manzoni, D., Porro, C. A., Francescato, M. P., Cettolo, V., Diamond, M. E., Baraldi, P., Bazzocchi, M., Rivosecchi, R., Konnerth, A., Rossi, M. L., Martini, M., Pelucchi, B., Fesce, R., Santarelli, L., Schacher, S., Montarolo, P. G., Santarelli, R., Grassi, C., Valente, A., Nisticò, S., Bagetta, G., Azzena, G. B., Scuri, Rossana, Garcia-Gil, Mercedes, Mozzachiodi, Riccardo, Brunelli, Marcello, Stefani, G., Onofri, F., Vaccaro, P., Nielander, H. B., Benfenati, F., Tancredi, V., D’Antuono, M., Siniscalchi, A., Brancati, A., Avoli, M., Vellani, V., Navangione, A., Rispoli, G., Verzè, L., Buffo, A., Rossi, F., Oestreicher, A. B., Gispen, W. H., Strata, P., Zamboni, G., Amici, R., Jones, C. A., Perez, E., Domeniconi, R., Parmeggiani, P. L., Zoli, Michele, Le Novàre, Nicolas, Changeux, Jean -Pierre, Lafortuna, C. L., Reinach, E., Saibene, F., Scotto, P., Zocchi, L., Agostoni, E., and Cremaschi, D.

Published
1996
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50. Very-low-calorie ketogenic diet (VLCKD) in the management of metabolic diseases: systematic review and consensus statement from the Italian Society of Endocrinology (SIE)

Author

Caprio M, Infante M, Moriconi E, Armani A, Fabbri A, Mantovani G, Maria, Biondi B, Cannavò S, I L, Prodam F, Aimaretti G, Linsalata G, Buralli S, Monzani F, Aversa A, Vettor R, Santini F, Vitti P, Gnessi L, Pagotto U, Giorgino F, Colao A, Lenzi A, Cardiovascular Endocrinology Club of the Italian Society of Endocrinology (Aldo Di Gregorio, Francesco Fallo, Carlo Foresta, Gilberta Giacchetti, Riccarda Granata, Andrea M Isidori, Paolo Magni, Pasquale Maiellaro, Mirko Parasiliti Caprino, Rosario Pivonello, Riccardo Pofi, Alfredo Pontecorvi, Chiara Simeoli, Caprio, M, Infante, M, Moriconi, E, Armani, A, Fabbri, A, Mantovani, G, Maria, Biondi, B, Cannavò, S, I, L, Prodam, F, Aimaretti, G, Linsalata, G, Buralli, S, Monzani, F, Aversa, A, Vettor, R, Santini, F, Vitti, P, Gnessi, L, Pagotto, U, Giorgino, F, Colao, A, Lenzi, A, Cardiovascular Endocrinology Club of the Italian Society of Endocrinology (Aldo Di, Gregorio, Francesco, Fallo, Carlo, Foresta, Gilberta, Giacchetti, Riccarda, Granata, Andrea, M Isidori, Paolo, Magni, Pasquale, Maiellaro, Mirko Parasiliti, Caprino, Rosario, Pivonello, Riccardo, Pofi, Alfredo, Pontecorvi, and Chiara, Simeoli

Published
2019

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