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2. The Potential Role of Vitamin D Supplementation In Cognitive Impairment Prevention

Author

Piffero R., Zeqaj I., Calzaducca E., Pirisi M., and Bellan M.

Subjects
Pharmacology, General Neuroscience
Abstract

Background: Vitamin D is implicated in many processes in the central nervous system (CNS), such as neurogenesis, neurotransmitter synthesis, synaptogenesis and protection against oxidative stress, thereby exerting a neuroprotective effect. Objective: In the present review, we aimed to evaluate the potential benefit(s) of vitamin D supplementation for CNS aging in different clinical contexts. Methods: We performed a literature search, looking for clinical trials and randomized clinical trials evaluating the effect of vitamin D supplementation on different endpoints related to cognitive outcomes. Results: Firstly, we identified 16 papers dealing with the impact of vitamin D supplementation on cognitive function in healthy subjects; the current literature suggests a real role for vitamin D supplementation in the prevention of cognitive decay in this clinical setting. Conversely, two papers suggest that vitamin D supplementation may be beneficial in patients with mild cognitive impairment (MCI). Finally, current data on vitamin D in Alzheimer’s disease are contradictory. Conclusion: Vitamin D supplementation may improve the cognitive outcomes of patients with MCI, whereas there is no evidence that it may prevent dementia or modulate the course of Alzheimer’s disease.

Published
2023
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3. Fatality rate and predictors of mortality in an Italian cohort of hospitalized COVID-19 patients

Author

Bellan, M, Patti, G, Hayden, E, Azzolina, D, Pirisi, M, Acquaviva, A, Aimaretti, G, Aluffi Valletti, P, Angilletta, R, Arioli, R, Avanzi, G, Avino, G, Balbo, P, Baldon, G, Baorda, F, Barbero, E, Baricich, A, Barini, M, Barone-Adesi, F, Battistini, S, Beltrame, M, Bertoli, M, Bertolin, S, Bertolotti, M, Betti, M, Bobbio, F, Boffano, P, Boglione, L, Borre, S, Brucoli, M, Calzaducca, E, Cammarata, E, Cantaluppi, V, Cantello, R, Capponi, A, Carriero, A, Casciaro, F, Castello, L, Ceruti, F, Chichino, G, Chirico, E, Cisari, C, Cittone, M, Colombo, C, Comi, C, Croce, E, Daffara, T, Danna, P, Della Corte, F, De Vecchi, S, Dianzani, U, Di Benedetto, D, Esposto, E, Faggiano, F, Falaschi, Z, Ferrante, D, Ferrero, A, Gagliardi, I, Gaidano, G, Galbiati, A, Gallo, S, Garavelli, P, Gardino, C, Garzaro, M, Gastaldello, M, Gavelli, F, Gennari, A, Giacomini, G, Giacone, I, Giai Via, V, Giolitti, F, Gironi, L, Gramaglia, C, Grisafi, L, Inserra, I, Invernizzi, M, Krengli, M, Labella, E, Landi, I, Landi, R, Leone, I, Lio, V, Lorenzini, L, Maconi, A, Malerba, M, Manfredi, G, Martelli, M, Marzari, L, Marzullo, P, Mennuni, M, Montabone, C, Morosini, U, Mussa, M, Nerici, I, Nuzzo, A, Olivieri, C, Padelli, S, Panella, M, Parisini, A, Pasche, A, Pau, A, Pedrinelli, A, Percivale, I, Re, R, Rigamonti, C, Rizzi, E, Rognoni, A, Roveta, A, Salamina, L, Santagostino, M, Saraceno, M, Savoia, P, Sciarra, M, Schimmenti, A, Scotti, L, Spinoni, E, Smirne, C, Tarantino, V, Tillio, P, Vaschetto, R, Vassia, V, Zagaria, D, Zavattaro, E, Zeppegno, P, Zottarelli, F, Sainaghi, P, Bellan M., Patti G., Hayden E., Azzolina D., Pirisi M., Acquaviva A., Aimaretti G., Aluffi Valletti P., Angilletta R., Arioli R., Avanzi G. C., Avino G., Balbo P. E., Baldon G., Baorda F., Barbero E., Baricich A., Barini M., Barone-Adesi F., Battistini S., Beltrame M., Bertoli M., Bertolin S., Bertolotti M., Betti M., Bobbio F., Boffano P., Boglione L., Borre S., Brucoli M., Calzaducca E., Cammarata E., Cantaluppi V., Cantello R., Capponi A., Carriero A., Casciaro F. G., Castello L. M., Ceruti F., Chichino G., Chirico E., Cisari C., Cittone M. G., Colombo C., Comi C., Croce E., Daffara T., Danna P., Della Corte F., De Vecchi S., Dianzani U., Di Benedetto D., Esposto E., Faggiano F., Falaschi Z., Ferrante D., Ferrero A., Gagliardi I., Gaidano G., Galbiati A., Gallo S., Garavelli P. L., Gardino C. A., Garzaro M., Gastaldello M. L., Gavelli F., Gennari A., Giacomini G. M., Giacone I., Giai Via V., Giolitti F., Gironi L. C., Gramaglia C., Grisafi L., Inserra I., Invernizzi M., Krengli M., Labella E., Landi I. C., Landi R., Leone I., Lio V., Lorenzini L., Maconi A., Malerba M., Manfredi G. F., Martelli M., Marzari L., Marzullo P., Mennuni M., Montabone C., Morosini U., Mussa M., Nerici I., Nuzzo A., Olivieri C., Padelli S. A., Panella M., Parisini A., Pasche A., Pau A., Pedrinelli A. R., Percivale I., Re R., Rigamonti C., Rizzi E., Rognoni A., Roveta A., Salamina L., Santagostino M., Saraceno M., Savoia P., Sciarra M., Schimmenti A., Scotti L., Spinoni E., Smirne C., Tarantino V., Tillio P. A., Vaschetto R., Vassia V., Zagaria D., Zavattaro E., Zeppegno P., Zottarelli F., Sainaghi P. P., Bellan, M, Patti, G, Hayden, E, Azzolina, D, Pirisi, M, Acquaviva, A, Aimaretti, G, Aluffi Valletti, P, Angilletta, R, Arioli, R, Avanzi, G, Avino, G, Balbo, P, Baldon, G, Baorda, F, Barbero, E, Baricich, A, Barini, M, Barone-Adesi, F, Battistini, S, Beltrame, M, Bertoli, M, Bertolin, S, Bertolotti, M, Betti, M, Bobbio, F, Boffano, P, Boglione, L, Borre, S, Brucoli, M, Calzaducca, E, Cammarata, E, Cantaluppi, V, Cantello, R, Capponi, A, Carriero, A, Casciaro, F, Castello, L, Ceruti, F, Chichino, G, Chirico, E, Cisari, C, Cittone, M, Colombo, C, Comi, C, Croce, E, Daffara, T, Danna, P, Della Corte, F, De Vecchi, S, Dianzani, U, Di Benedetto, D, Esposto, E, Faggiano, F, Falaschi, Z, Ferrante, D, Ferrero, A, Gagliardi, I, Gaidano, G, Galbiati, A, Gallo, S, Garavelli, P, Gardino, C, Garzaro, M, Gastaldello, M, Gavelli, F, Gennari, A, Giacomini, G, Giacone, I, Giai Via, V, Giolitti, F, Gironi, L, Gramaglia, C, Grisafi, L, Inserra, I, Invernizzi, M, Krengli, M, Labella, E, Landi, I, Landi, R, Leone, I, Lio, V, Lorenzini, L, Maconi, A, Malerba, M, Manfredi, G, Martelli, M, Marzari, L, Marzullo, P, Mennuni, M, Montabone, C, Morosini, U, Mussa, M, Nerici, I, Nuzzo, A, Olivieri, C, Padelli, S, Panella, M, Parisini, A, Pasche, A, Pau, A, Pedrinelli, A, Percivale, I, Re, R, Rigamonti, C, Rizzi, E, Rognoni, A, Roveta, A, Salamina, L, Santagostino, M, Saraceno, M, Savoia, P, Sciarra, M, Schimmenti, A, Scotti, L, Spinoni, E, Smirne, C, Tarantino, V, Tillio, P, Vaschetto, R, Vassia, V, Zagaria, D, Zavattaro, E, Zeppegno, P, Zottarelli, F, Sainaghi, P, Bellan M., Patti G., Hayden E., Azzolina D., Pirisi M., Acquaviva A., Aimaretti G., Aluffi Valletti P., Angilletta R., Arioli R., Avanzi G. C., Avino G., Balbo P. E., Baldon G., Baorda F., Barbero E., Baricich A., Barini M., Barone-Adesi F., Battistini S., Beltrame M., Bertoli M., Bertolin S., Bertolotti M., Betti M., Bobbio F., Boffano P., Boglione L., Borre S., Brucoli M., Calzaducca E., Cammarata E., Cantaluppi V., Cantello R., Capponi A., Carriero A., Casciaro F. G., Castello L. M., Ceruti F., Chichino G., Chirico E., Cisari C., Cittone M. G., Colombo C., Comi C., Croce E., Daffara T., Danna P., Della Corte F., De Vecchi S., Dianzani U., Di Benedetto D., Esposto E., Faggiano F., Falaschi Z., Ferrante D., Ferrero A., Gagliardi I., Gaidano G., Galbiati A., Gallo S., Garavelli P. L., Gardino C. A., Garzaro M., Gastaldello M. L., Gavelli F., Gennari A., Giacomini G. M., Giacone I., Giai Via V., Giolitti F., Gironi L. C., Gramaglia C., Grisafi L., Inserra I., Invernizzi M., Krengli M., Labella E., Landi I. C., Landi R., Leone I., Lio V., Lorenzini L., Maconi A., Malerba M., Manfredi G. F., Martelli M., Marzari L., Marzullo P., Mennuni M., Montabone C., Morosini U., Mussa M., Nerici I., Nuzzo A., Olivieri C., Padelli S. A., Panella M., Parisini A., Pasche A., Pau A., Pedrinelli A. R., Percivale I., Re R., Rigamonti C., Rizzi E., Rognoni A., Roveta A., Salamina L., Santagostino M., Saraceno M., Savoia P., Sciarra M., Schimmenti A., Scotti L., Spinoni E., Smirne C., Tarantino V., Tillio P. A., Vaschetto R., Vassia V., Zagaria D., Zavattaro E., Zeppegno P., Zottarelli F., and Sainaghi P. P.

Abstract

Clinical features and natural history of coronavirus disease 2019 (COVID-19) differ widely among different countries and during different phases of the pandemia. Here, we aimed to evaluate the case fatality rate (CFR) and to identify predictors of mortality in a cohort of COVID-19 patients admitted to three hospitals of Northern Italy between March 1 and April 28, 2020. All these patients had a confirmed diagnosis of SARS-CoV-2 infection by molecular methods. During the study period 504/1697 patients died; thus, overall CFR was 29.7%. We looked for predictors of mortality in a subgroup of 486 patients (239 males, 59%; median age 71 years) for whom sufficient clinical data were available at data cut-off. Among the demographic and clinical variables considered, age, a diagnosis of cancer, obesity and current smoking independently predicted mortality. When laboratory data were added to the model in a further subgroup of patients, age, the diagnosis of cancer, and the baseline PaO2/FiO2 ratio were identified as independent predictors of mortality. In conclusion, the CFR of hospitalized patients in Northern Italy during the ascending phase of the COVID-19 pandemic approached 30%. The identification of mortality predictors might contribute to better stratification of individual patient risk.

Published
2020

4. Simple parameters from complete blood count predict in-hospital mortality in covid-19

Author

Bellan, M., Azzolina, D., Hayden, E., Gaidano, G., Pirisi, M., Acquaviva, A., Aimaretti, G., Valletti, P. A., Angilletta, R., Arioli, R., Avanzi, G. C., Avino, G., Balbo, P. E., Baldon, G., Baorda, F., Barbero, E., Baricich, A., Barini, M., Barone-Adesi, F., Battistini, S., Beltrame, M., Bertoli, M., Bertolin, S., Bertolotti, M., Betti, M., Bobbio, F., Boffano, P., Boglione, L., Borre, S., Brucoli, M., Calzaducca, E., Cammarata, E., Cantaluppi, V., Cantello, R., Capponi, A., Carriero, A., Casciaro, G. F., Castello, L. M., Ceruti, F., Chichino, G., Chirico, E., Cisari, C., Cittone, M. G., Colombo, C., Comi, C., Croce, E., Daffara, T., Danna, P., Corte, F. D., de Vecchi, S., Dianzani, U., Benedetto, D. D., Esposto, E., Faggiano, F., Falaschi, Z., Ferrante, D., Ferrero, A., Gagliardi, I., Galbiati, A., Gallo, S., Garavelli, P. L., Gardino, C. A., Garzaro, M., Gastaldello, M. L., Gavelli, F., Gennari, A., Giacomini, G. M., Giacone, I., Via, V. G., Giolitti, F., Gironi, L. C., Gramaglia, C., Grisafi, L., Inserra, I., Invernizzi, M., Krengli, M., Labella, E., Landi, I. C., Landi, R., Leone, I., Lio, V., Lorenzini, L., Maconi, A., Malerba, M., Manfredi, G. F., Martelli, M., Marzari, L., Marzullo, P., Mennuni, M., Montabone, C., Morosini, U., Mussa, M., Nerici, I., Nuzzo, A., Olivieri, C., Padelli, S. A., Panella, M., Parisini, A., Pasche, A., Patrucco, F., Patti, G., Pau, A., Pedrinelli, A. R., Percivale, I., Ragazzoni, L., Re, R., Rigamonti, C., Rizzi, E., Rognoni, A., Roveta, A., Salamina, L., Santagostino, M., Saraceno, M., Savoia, P., Sciarra, M., Schimmenti, A., Scotti, L., Spinoni, E., Smirne, C., Tarantino, V., Tillio, P. A., Tonello, S., Vaschetto, R., Vassia, V., Zagaria, D., Zavattaro, E., Zeppegno, P., Zottarelli, F., Sainaghi, P. P., Aiosa, G., Airoldi, A., Barco, A., Bargiacchi, O., Bazzano, S., Berni, P., Bianchi, B., Bianco, S., Biffi, S., Binda, V., Bolgeo, T., Bolla, C., Bonato, V., Bonizzoni, G., Bragantini, A., Brustia, D., Bullara, V., Burlone, M., Brustia, F., Caccia, S., Calareso, A., Cammarota, G., Cancelliere, L., Carbone, R., Cassinari, A., Ceriani, E., Cena, T., Clivati, E., Collimedaglia, L., Colombatto, A., Cornella, C., Costanzo, M., Croce, A., de Benedittis, C., Delorenzi, S., Dionisio, R., Donato, P., Esposito, M., Fangazio, S., Feggi, A., Ferrillo, S., Foci, V., Fra, G. P., Gaggino, C., Gambaro, E., Gattoni, E., Gattoni, L., Giacchero, F., Gianfreda, R., Giubertoni, A., Grecu, L., Grossi, F., Guglielmetti, G., Guido, S., Iannantuoni, G., Ingrao, S., Jona, A., Lazzarich, E., Lissandrin, R., Maduli, E., Magne, F., Mantia, E., Marangon, D., Massara, M., Matino, E., Mauri, M. G., Menegatti, M., Moglia, R., Molinari, R., Morelli, S., Morlino, P., Naldi, P., Nebbiolo, C., Omodeo, P., Palmieri, D., Panero, A., Parodi, M., Pedrazzoli, R., Pelazza, C., Penpa, S., Perucca, R., Pirovano, A., Pittau, S., Pochetti, P., Poletti, F., Polla, B., Prandi, P., Prodam, F., Prosperini, P., Puma, A., Quaglia, M., Raie, A., Rapetti, R., Ravera, S., Re, A., Reale, M., Rossati, A., Rossi, M., Rossi, P., Rostagno, R., Salomoni, G., Sama, M. T., Sarchi, E., Sarcoli, M., Sarda, C., Sguazzotti, I., Soddu, D., Sola, D., Stobbione, P., Todoerti, M., Vallese, G. C., Varrasi, C., Veia, A., Vignazia, G. L., Zanotti, I., Zecca, E., Zichittella, D., Zisa, G., and Zoppis, E.

Subjects
Adult, Male, medicine.medical_specialty, Medicine (General), Multivariate analysis, Article Subject, Clinical Decision Rules, COVID-19, Prognosis, Blood Cell Count, Hospital Mortality, Severity of Illness Index, Clinical Biochemistry, Asymptomatic, Severity of Illness Index, NO, R5-920, Internal medicine, Clinical Decision Rules, Severity of illness, Genetics, 80 and over, Medicine, Humans, Hospital Mortality, Molecular Biology, Aged, Retrospective Studies, Aged, 80 and over, medicine.diagnostic_test, business.industry, Biochemistry (medical), Complete blood count, COVID-19, Retrospective cohort study, Red blood cell distribution width, General Medicine, Odds ratio, Middle Aged, Prognosis, Female, Italy, Multivariate Analysis, Blood Cell Count, Cohort, medicine.symptom, business, Research Article
Abstract

Introduction. The clinical course of Coronavirus Disease 2019 (COVID-19) is highly heterogenous, ranging from asymptomatic to fatal forms. The identification of clinical and laboratory predictors of poor prognosis may assist clinicians in monitoring strategies and therapeutic decisions. Materials and Methods. In this study, we retrospectively assessed the prognostic value of a simple tool, the complete blood count, on a cohort of 664 patients ( F 260; 39%, median age 70 (56-81) years) hospitalized for COVID-19 in Northern Italy. We collected demographic data along with complete blood cell count; moreover, the outcome of the hospital in-stay was recorded. Results. At data cut-off, 221/664 patients (33.3%) had died and 453/664 (66.7%) had been discharged. Red cell distribution width (RDW) ( χ 2 10.4; p < 0.001 ), neutrophil-to-lymphocyte (NL) ratio ( χ 2 7.6; p = 0.006 ), and platelet count ( χ 2 5.39; p = 0.02 ), along with age ( χ 2 87.6; p < 0.001 ) and gender ( χ 2 17.3; p < 0.001 ), accurately predicted in-hospital mortality. Hemoglobin levels were not associated with mortality. We also identified the best cut-off for mortality prediction: a NL ratio > 4.68 was characterized by an odds ratio for in-hospital mortality OR = 3.40 (2.40-4.82), while the OR for a RDW > 13.7 % was 4.09 (2.87-5.83); a platelet count > 166,000 /μL was, conversely, protective (OR: 0.45 (0.32-0.63)). Conclusion. Our findings arise the opportunity of stratifying COVID-19 severity according to simple lab parameters, which may drive clinical decisions about monitoring and treatment.

Published
2021

6. Fatality rate and predictors of mortality in an Italian cohort of hospitalized COVID-19 patients

Author

Lucio Boglione, Irene Cecilia Landi, Marinella Bertolotti, Alessandra Galbiati, Luca Lorenzini, Carlo Cisari, Luigia Salamina, Matteo Brucoli, Irene Giacone, Carlo Olivieri, Flavio Bobbio, Marta Betti, Maria Martelli, Paolo Amedeo Tillio, Vanessa Tarantino, Anita R. Pedrinelli, Mario Pirisi, Pietro Luigi Garavelli, Eleonora Croce, Alessandra Gennari, Francesca Zottarelli, Pietro Danna, Marco Invernizzi, Antonio Maconi, Francesca Giolitti, Sofia Battistini, Paolo Marzullo, Roberta Re, Domenico Zagaria, Francesco Gavelli, Federico Ceruti, Ilaria Leone, Greta Maria Giacomini, Leonardo Grisafi, Andrea Parisini, Stephanie Bertolin, Elia Esposto, Vincenzo Cantaluppi, Mattia Bellan, Giuseppe Patti, Emilio Chirico, Matteo Bertoli, Paolo Boffano, Paolo Aluffi Valletti, Alessandro Carriero, Cristoforo Comi, Umberto Dianzani, Eleonora Rizzi, Massimiliano Panella, Marco Sciarra, Edoardo Cammarata, Letizia Marzari, Elisa Zavattaro, Claudia Montabone, Gian Carlo Avanzi, Samuel Alberto Padelli, Massimiliano Garzaro, Pier Paolo Sainaghi, Francesco Barone-Adesi, Carlo Smirne, Gianluca Gaidano, Michela Barini, Francesco Giuseppe Casciaro, Ilaria Inserra, Laura Cristina Gironi, Ilaria Nerici, Clara Ada Gardino, Maria Luisa Gastaldello, Micol Giulia Cittone, Marco Mussa, Umberto Morosini, Andrea Capponi, Davide Di Benedetto, Fabrizio Faggiano, Crizia Colombo, Andrea Rognoni, Elisa Calzaducca, Alessio Paschè, Annalisa Roveta, Gianluca Aimaretti, Roberto Arioli, Giulia Baldon, Roberto Cantello, Ilaria Percivale, Piero Emilio Balbo, Emanuela Barbero, Silvio Borrè, Luigi Mario Castello, Patrizia Zeppegno, Ileana Gagliardi, Emanuela Labella, Alice Ferrero, Marco Krengli, Silvia Gallo, Andrea Schimmenti, Tommaso Daffara, Raffaella Landi, Paola Savoia, Giulia Francesca Manfredi, Valentina Giai Via, Michela Beltrame, Eyal Hayden, Enrico Guido Spinoni, Francesca Baorda, Cristina Rigamonti, Alessandro Nuzzo, Mario Malerba, Carla Gramaglia, Rosanna Vaschetto, Massimo Saraceno, Gianluca Avino, Marco G. Mennuni, Daniela Ferrante, Guido Chichino, Danila Azzolina, Alessio Baricich, Veronica Lio, Veronica Vassia, Alberto Pau, Roberto Angilletta, Simona De Vecchi, Antonio Acquaviva, Lorenza Scotti, Francesco Della Corte, Matteo Santagostino, Zeno Falaschi, Bellan, M, Patti, G, Hayden, E, Azzolina, D, Pirisi, M, Acquaviva, A, Aimaretti, G, Aluffi Valletti, P, Angilletta, R, Arioli, R, Avanzi, G, Avino, G, Balbo, P, Baldon, G, Baorda, F, Barbero, E, Baricich, A, Barini, M, Barone-Adesi, F, Battistini, S, Beltrame, M, Bertoli, M, Bertolin, S, Bertolotti, M, Betti, M, Bobbio, F, Boffano, P, Boglione, L, Borre, S, Brucoli, M, Calzaducca, E, Cammarata, E, Cantaluppi, V, Cantello, R, Capponi, A, Carriero, A, Casciaro, F, Castello, L, Ceruti, F, Chichino, G, Chirico, E, Cisari, C, Cittone, M, Colombo, C, Comi, C, Croce, E, Daffara, T, Danna, P, Della Corte, F, De Vecchi, S, Dianzani, U, Di Benedetto, D, Esposto, E, Faggiano, F, Falaschi, Z, Ferrante, D, Ferrero, A, Gagliardi, I, Gaidano, G, Galbiati, A, Gallo, S, Garavelli, P, Gardino, C, Garzaro, M, Gastaldello, M, Gavelli, F, Gennari, A, Giacomini, G, Giacone, I, Giai Via, V, Giolitti, F, Gironi, L, Gramaglia, C, Grisafi, L, Inserra, I, Invernizzi, M, Krengli, M, Labella, E, Landi, I, Landi, R, Leone, I, Lio, V, Lorenzini, L, Maconi, A, Malerba, M, Manfredi, G, Martelli, M, Marzari, L, Marzullo, P, Mennuni, M, Montabone, C, Morosini, U, Mussa, M, Nerici, I, Nuzzo, A, Olivieri, C, Padelli, S, Panella, M, Parisini, A, Pasche, A, Pau, A, Pedrinelli, A, Percivale, I, Re, R, Rigamonti, C, Rizzi, E, Rognoni, A, Roveta, A, Salamina, L, Santagostino, M, Saraceno, M, Savoia, P, Sciarra, M, Schimmenti, A, Scotti, L, Spinoni, E, Smirne, C, Tarantino, V, Tillio, P, Vaschetto, R, Vassia, V, Zagaria, D, Zavattaro, E, Zeppegno, P, Zottarelli, F, and Sainaghi, P

Subjects
Male, COVID-19, Viral infection, Risk factors, lcsh:Medicine, Comorbidity, Sex Factor, 030204 cardiovascular system & hematology, 0302 clinical medicine, Retrospective Studie, Case fatality rate, Pandemic, Age Factor, 030212 general & internal medicine, lcsh:Science, clinical characteristics, Aged, 80 and over, Multidisciplinary, Reverse Transcriptase Polymerase Chain Reaction, Smoking, Age Factors, Middle Aged, Coronavirus disease, Natural history, Survival Rate, Italy, Cohort, Female, Human, medicine.medical_specialty, Article, NO, 03 medical and health sciences, Sex Factors, Internal medicine, medicine, Humans, Pandemics, Survival rate, Retrospective Studies, Aged, business.industry, SARS-CoV-2, Risk Factor, lcsh:R, Retrospective cohort study, Length of Stay, medicine.disease, Obesity, lcsh:Q, Coronavirus disease, clinical characteristics, business
Abstract

Clinical features and natural history of coronavirus disease 2019 (COVID-19) differ widely among different countries and during different phases of the pandemia. Here, we aimed to evaluate the case fatality rate (CFR) and to identify predictors of mortality in a cohort of COVID-19 patients admitted to three hospitals of Northern Italy between March 1 and April 28, 2020. All these patients had a confirmed diagnosis of SARS-CoV-2 infection by molecular methods. During the study period 504/1697 patients died; thus, overall CFR was 29.7%. We looked for predictors of mortality in a subgroup of 486 patients (239 males, 59%; median age 71 years) for whom sufficient clinical data were available at data cut-off. Among the demographic and clinical variables considered, age, a diagnosis of cancer, obesity and current smoking independently predicted mortality. When laboratory data were added to the model in a further subgroup of patients, age, the diagnosis of cancer, and the baseline PaO2/FiO2 ratio were identified as independent predictors of mortality. In conclusion, the CFR of hospitalized patients in Northern Italy during the ascending phase of the COVID-19 pandemic approached 30%. The identification of mortality predictors might contribute to better stratification of individual patient risk.

Published
2020

7. Ongoing Mycophenolate Treatment Impairs Anti-SARS-CoV-2 Vaccination Response in Patients Affected by Chronic Inflammatory Autoimmune Diseases or Liver Transplantation Recipients: Results of the RIVALSA Prospective Cohort.

Author

Zecca E, Rizzi M, Tonello S, Matino E, Costanzo M, Rizzi E, Casciaro GF, Manfredi GF, Acquaviva A, Gagliardi I, Calzaducca E, Mallela VR, D'Onghia D, Minisini R, Bellan M, Castello LM, Gavelli F, Avanzi GC, Patrucco F, Chiocchetti A, Pirisi M, Rigamonti C, Lilleri D, Sola D, and Sainaghi PP

Subjects
Antibodies, Viral, COVID-19 Vaccines, Humans, Immunoglobulin G, Immunosuppressive Agents therapeutic use, Prospective Studies, RNA, Messenger, SARS-CoV-2, Vaccination, Vaccines, Synthetic, mRNA Vaccines, Autoimmune Diseases drug therapy, COVID-19 prevention & control, Liver Transplantation, Viral Vaccines
Abstract

Vaccines are the most effective means to prevent the potentially deadly effects of SARS-CoV-2 infection, but not all vaccinated individuals gain the same degree of protection. Patients undergoing chronic immunosuppressive therapy due to autoimmune diseases or liver transplants, for example, may show impaired anti-SARS-CoV-2 antibody response after vaccination. We performed a prospective observational study with parallel arms, aiming to (a) evaluate seroconversion after anti-SARS-CoV-2 mRNA vaccine administration in different subgroups of patients receiving immunosuppressive treatment for rheumatological or autoimmune diseases or to prevent organ rejection after liver transplantation and (b) identify negative predictors of IgG anti-SARS-CoV-2 development. Out of 437 eligible patients, 183 individuals were enrolled at the Rheumatology and Hepatology Tertiary Units of “Maggiore della Carità” University Hospital in Novara: of those, 52 were healthy subjects, while among the remaining 131 patients, 30 had a diagnosis of spondyloarthritis, 25 had autoimmune hepatitis, 10 were liver transplantation recipients, 23 suffered from connective tissue diseases (including 10 cases that overlapped with other diseases), 40 were treated for rheumatoid arthritis, and 5 had vasculitis. Moreover, all patients were receiving chronic immunosuppressive therapy. The immunogenicity of mRNA COVID-19 vaccines was evaluated by measuring IgG anti-SARS-CoV-2 antibody titers before vaccination and after 10, 30, and 90 days since the first dose administration. Of the selected cohort of patients, 24.0% did not develop any detectable anti-SARS-CoV-2 IgG after a complete mRNA-based two doses primary vaccination cycle. At univariate analysis, independent predictors of an absent antibody response to vaccine were a history of liver transplantation (OR 11.5, 95% CI 2.5−53.7, p = 0.0018), the presence of a comorbid active neoplasia (OR 26.4, 95% CI 2.8−252.4, p = 0.0045), and an ongoing immunosuppressive treatment with mycophenolate (MMF) (OR 14.0, 95% CI 3.6−54.9, p = 0.0002) or with calcineurin inhibitors (OR 17.5, 95% CI 3.1−99.0, p = 0.0012). At multivariate analysis, only treatment with MMF (OR 24.8, 95% CI 5.9−103.2, p < 0.0001) and active neoplasia (OR 33.2, 95% CI 5.4−204.1, p = 0.0002) were independent predictors of seroconversion failure. These findings suggest that MMF dose reduction or suspension may be required to optimize vaccine response in these patients.

Published
2022
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8. Risk of Severe Infection among Rheumatoid Arthritis Patients on Biological DMARDs: A Population-Based Cohort Study.

Author

Bellan M, Scotti L, Ferrante D, Calzaducca E, Manfredi GF, Sainaghi PP, and Barone-Adesi F

Abstract

Biological disease-modifying anti-rheumatic drugs (bDMARDs) are widely used for the management of rheumatoid arthritis, although their benefits are counterweight by an increased risk of infections. In the present study, we used administrative data to compare the risk of severe infections among different classes of bDMARDs. A retrospective cohort study was conducted using Administrative Health Databases of the Piedmont Region, Italy. Relevant data were obtained from: (1) the inhabitants registry, (2) hospital discharge records, and (3) the co-payment exemption registry and (4) drug claims registry. Fine and Gray competing risk models were fitted to evaluate the association between the use of different types of bDMARDs and occurrence of severe infection accounting for treatment interruption as competing risk. A total of 1780 new users of bDMARDs were identified. Among them, 50 hospitalizations for infection occurred during the study period. The use of Tocilizumab was associated with an increased risk of infection, compared to tumor necrosis factor (TNF) inhibitor drugs (sub-distribution hazard ratios-sHR: 2.510; 95% CI: 1.279-4.926), whereas no difference in the risk of severe infection was found for abatacept (sHR: 0.584; 95% CI: 0.234-1.457). bDMARDs treatment is generally safe in clinical practice with slight but important differences among classes. The increased risk of infection associated with tocilizumab use should be taken into account when balancing the risk and benefits of starting a treatment with this drug.

Published
2022
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9. Simple Parameters from Complete Blood Count Predict In-Hospital Mortality in COVID-19.

Author

Bellan M, Azzolina D, Hayden E, Gaidano G, Pirisi M, Acquaviva A, Aimaretti G, Aluffi Valletti P, Angilletta R, Arioli R, Avanzi GC, Avino G, Balbo PE, Baldon G, Baorda F, Barbero E, Baricich A, Barini M, Barone-Adesi F, Battistini S, Beltrame M, Bertoli M, Bertolin S, Bertolotti M, Betti M, Bobbio F, Boffano P, Boglione L, Borrè S, Brucoli M, Calzaducca E, Cammarata E, Cantaluppi V, Cantello R, Capponi A, Carriero A, Casciaro GF, Castello LM, Ceruti F, Chichino G, Chirico E, Cisari C, Cittone MG, Colombo C, Comi C, Croce E, Daffara T, Danna P, Della Corte F, De Vecchi S, Dianzani U, Di Benedetto D, Esposto E, Faggiano F, Falaschi Z, Ferrante D, Ferrero A, Gagliardi I, Galbiati A, Gallo S, Garavelli PL, Gardino CA, Garzaro M, Gastaldello ML, Gavelli F, Gennari A, Giacomini GM, Giacone I, Giai Via V, Giolitti F, Gironi LC, Gramaglia C, Grisafi L, Inserra I, Invernizzi M, Krengli M, Labella E, Landi IC, Landi R, Leone I, Lio V, Lorenzini L, Maconi A, Malerba M, Manfredi GF, Martelli M, Marzari L, Marzullo P, Mennuni M, Montabone C, Morosini U, Mussa M, Nerici I, Nuzzo A, Olivieri C, Padelli SA, Panella M, Parisini A, Paschè A, Patrucco F, Patti G, Pau A, Pedrinelli AR, Percivale I, Ragazzoni L, Re R, Rigamonti C, Rizzi E, Rognoni A, Roveta A, Salamina L, Santagostino M, Saraceno M, Savoia P, Sciarra M, Schimmenti A, Scotti L, Spinoni E, Smirne C, Tarantino V, Tillio PA, Tonello S, Vaschetto R, Vassia V, Zagaria D, Zavattaro E, Zeppegno P, Zottarelli F, and Sainaghi PP

Subjects
Adult, Aged, Aged, 80 and over, COVID-19 diagnosis, Female, Humans, Italy epidemiology, Male, Middle Aged, Multivariate Analysis, Prognosis, Retrospective Studies, Blood Cell Count, COVID-19 blood, COVID-19 mortality, Clinical Decision Rules, Hospital Mortality, Severity of Illness Index
Abstract

Introduction: The clinical course of Coronavirus Disease 2019 (COVID-19) is highly heterogenous, ranging from asymptomatic to fatal forms. The identification of clinical and laboratory predictors of poor prognosis may assist clinicians in monitoring strategies and therapeutic decisions., Materials and Methods: In this study, we retrospectively assessed the prognostic value of a simple tool, the complete blood count, on a cohort of 664 patients ( F 260; 39%, median age 70 (56-81) years) hospitalized for COVID-19 in Northern Italy. We collected demographic data along with complete blood cell count; moreover, the outcome of the hospital in-stay was recorded., Results: At data cut-off, 221/664 patients (33.3%) had died and 453/664 (66.7%) had been discharged. Red cell distribution width (RDW) ( χ 2 10.4; p < 0.001), neutrophil-to-lymphocyte (NL) ratio ( χ 2 7.6; p = 0.006), and platelet count ( χ 2 5.39; p = 0.02), along with age ( χ 2 87.6; p < 0.001) and gender ( χ 2 17.3; p < 0.001), accurately predicted in-hospital mortality. Hemoglobin levels were not associated with mortality. We also identified the best cut-off for mortality prediction: a NL ratio > 4.68 was characterized by an odds ratio for in-hospital mortality (OR) = 3.40 (2.40-4.82), while the OR for a RDW > 13.7% was 4.09 (2.87-5.83); a platelet count > 166,000/ μ L was, conversely, protective (OR: 0.45 (0.32-0.63))., Conclusion: Our findings arise the opportunity of stratifying COVID-19 severity according to simple lab parameters, which may drive clinical decisions about monitoring and treatment., Competing Interests: The authors have no conflict of interest to declare., (Copyright © 2021 Mattia Bellan et al.)

Published
2021
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10. Role of Osteopontin as a Potential Biomarker of Pulmonary Arterial Hypertension in Patients with Systemic Sclerosis and Other Connective Tissue Diseases (CTDs).

Author

Bellan M, Piccinino C, Tonello S, Minisini R, Giubertoni A, Sola D, Pedrazzoli R, Gagliardi I, Zecca E, Calzaducca E, Mazzoleni F, Piffero R, Patti G, Pirisi M, and Sainaghi PP

Abstract

Pulmonary arterial hypertension (PAH) is a severe complication of connective tissue diseases (CTD). Its early diagnosis is essential to start effective treatment. In the present paper, we aimed to evaluate the role of plasma osteopontin (OPN) as a candidate biomarker of PAH in a cohort of CTD patients. OPN is a pleiotropic protein involved in inflammation and fibrogenesis and, therefore, potentially promising in this specific clinical context. We performed a cross-sectional observational study on a cohort of 113 CTD patients (females N = 101, 89.4%) affected by systemic sclerosis N = 88 (77.9%), mixed connective tissue disease N = 10 (8.8%), overlap syndrome N = 10 (8.8%) or undifferentiated connective tissue disease N = 5 (4.4%). CTD-PAH patients showed significantly higher OPN plasma values than patients with CTD alone (241.0 (188.8-387.2) vs. 200.7 (133.5-281.6) ng/mL; p = 0.03). Although OPN levels were directly correlated with age and inversely with glomerular filtration rate, they remained associated with PAH at multivariate analysis. In conclusion, OPN was significantly associated with PAH among patients with CTD, suggesting it may have a role as a non-invasive disease biomarker of PAH.

Published
2021
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11. Cardiopulmonary Exercise Testing Is an Accurate Tool for the Diagnosis of Pulmonary Arterial Hypertension in Scleroderma Related Diseases.

Author

Bellan M, Giubertoni A, Piccinino C, Buffa M, Cromi D, Sola D, Pedrazzoli R, Gagliardi I, Calzaducca E, Zecca E, Patrucco F, Patti G, Sainaghi PP, and Pirisi M

Abstract

The early diagnosis of pulmonary arterial hypertension (PAH) is a major determinant of prognosis in patients affected by connective tissue diseases (CTDs) complicated by PAH. In the present paper we investigated the diagnostic accuracy of cardiopulmonary exercise testing (CPET) in this specific setting. We recorded clinical and laboratory data of 131 patients who underwent a CPET at a pulmonary hypertension clinic. Out of them, 112 (85.5%) had a diagnosis of CTDs; 8 (6.1%) received a diagnosis of CTDs-PAH and 11 (8.4%) were affected PH of different etiology. Among CPET parameters the following parameters showed the best diagnostic performance for PAH: peak volume of oxygen uptake (VO 2 ; AUC: 0.845, CI95% 0.767-0.904), ratio between ventilation and volume of exhaled carbon dioxide (VE/VCO 2 slope; AUC: 0.888, CI95%: 0.817-0.938) and end-tidal partial pressures (PetCO 2 ; AUC: 0.792, CI95%: 0.709-0.861). These parameters were comparable among CTDs-PAH and PH of different etiology. The diagnostic performance was even improved by creating a composite score which included all the three parameters identified. In conclusion, CPET is a very promising tool for the stratification of risk of PAH among CTDs patients; the use of composite measures may improve diagnostic performance.

Published
2021
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12. Fatality rate and predictors of mortality in an Italian cohort of hospitalized COVID-19 patients.

Author

Bellan M, Patti G, Hayden E, Azzolina D, Pirisi M, Acquaviva A, Aimaretti G, Aluffi Valletti P, Angilletta R, Arioli R, Avanzi GC, Avino G, Balbo PE, Baldon G, Baorda F, Barbero E, Baricich A, Barini M, Barone-Adesi F, Battistini S, Beltrame M, Bertoli M, Bertolin S, Bertolotti M, Betti M, Bobbio F, Boffano P, Boglione L, Borrè S, Brucoli M, Calzaducca E, Cammarata E, Cantaluppi V, Cantello R, Capponi A, Carriero A, Casciaro FG, Castello LM, Ceruti F, Chichino G, Chirico E, Cisari C, Cittone MG, Colombo C, Comi C, Croce E, Daffara T, Danna P, Della Corte F, De Vecchi S, Dianzani U, Di Benedetto D, Esposto E, Faggiano F, Falaschi Z, Ferrante D, Ferrero A, Gagliardi I, Gaidano G, Galbiati A, Gallo S, Garavelli PL, Gardino CA, Garzaro M, Gastaldello ML, Gavelli F, Gennari A, Giacomini GM, Giacone I, Giai Via V, Giolitti F, Gironi LC, Gramaglia C, Grisafi L, Inserra I, Invernizzi M, Krengli M, Labella E, Landi IC, Landi R, Leone I, Lio V, Lorenzini L, Maconi A, Malerba M, Manfredi GF, Martelli M, Marzari L, Marzullo P, Mennuni M, Montabone C, Morosini U, Mussa M, Nerici I, Nuzzo A, Olivieri C, Padelli SA, Panella M, Parisini A, Paschè A, Pau A, Pedrinelli AR, Percivale I, Re R, Rigamonti C, Rizzi E, Rognoni A, Roveta A, Salamina L, Santagostino M, Saraceno M, Savoia P, Sciarra M, Schimmenti A, Scotti L, Spinoni E, Smirne C, Tarantino V, Tillio PA, Vaschetto R, Vassia V, Zagaria D, Zavattaro E, Zeppegno P, Zottarelli F, and Sainaghi PP

Subjects
Age Factors, Aged, Aged, 80 and over, COVID-19 virology, Comorbidity, Female, Humans, Italy epidemiology, Length of Stay, Male, Middle Aged, Retrospective Studies, Reverse Transcriptase Polymerase Chain Reaction, Risk Factors, Sex Factors, Smoking, Survival Rate, COVID-19 epidemiology, COVID-19 mortality, Pandemics, SARS-CoV-2 genetics
Abstract

Clinical features and natural history of coronavirus disease 2019 (COVID-19) differ widely among different countries and during different phases of the pandemia. Here, we aimed to evaluate the case fatality rate (CFR) and to identify predictors of mortality in a cohort of COVID-19 patients admitted to three hospitals of Northern Italy between March 1 and April 28, 2020. All these patients had a confirmed diagnosis of SARS-CoV-2 infection by molecular methods. During the study period 504/1697 patients died; thus, overall CFR was 29.7%. We looked for predictors of mortality in a subgroup of 486 patients (239 males, 59%; median age 71 years) for whom sufficient clinical data were available at data cut-off. Among the demographic and clinical variables considered, age, a diagnosis of cancer, obesity and current smoking independently predicted mortality. When laboratory data were added to the model in a further subgroup of patients, age, the diagnosis of cancer, and the baseline PaO 2 /FiO 2 ratio were identified as independent predictors of mortality. In conclusion, the CFR of hospitalized patients in Northern Italy during the ascending phase of the COVID-19 pandemic approached 30%. The identification of mortality predictors might contribute to better stratification of individual patient risk.

Published
2020
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