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4. Direct use of eazyplex® SuperBug CRE assay from positive blood cultures in conjunction with inpatient infectious disease consulting for timely appropriate antimicrobial therapy in Escherichia coli and Klebsiella pneumoniae bloodstream infections

Author

Fiori B, D'Inzeo T, Posteraro B, Menchinelli G, Liotti FM, De Angelis G, De Maio F, Fantoni M, Murri R, Scoppettuolo G, Ventura G, Tumbarello M, Pennestrì F, Taccari F, Sanguinetti M, and Spanu T

Subjects
Escherichia coli, Klebsiella pneumoniae, bloodstream infection, drug resistance, targeted therapy, infectious disease consultation, Infectious and parasitic diseases, RC109-216
Abstract

Barbara Fiori,1–3,* Tiziana D’Inzeo,2,3,* Brunella Posteraro,4,5 Giulia Menchinelli,3 Flora Marzia Liotti,3 Giulia De Angelis,2,3 Flavio De Maio,3 Massimo Fantoni,6,7 Rita Murri,6,7 Giancarlo Scoppettuolo,6 Giulio Ventura,6 Mario Tumbarello,6,7 Francesco Pennestrì,4 Francesco Taccari,7 Maurizio Sanguinetti,2,3 Teresa Spanu2,31Scuola Provinciale Superiore di Sanità Claudiana, Bolzano, Italy; 2Fondazione Policlinico Universitario A. Gemelli IRCCS, Dipartimento di Scienze di Laboratorio e Infettivologiche, Rome, Italy; 3Università Cattolica del Sacro Cuore, Istituto di Microbiologia, Rome, Italy; 4Fondazione Policlinico Universitario A. Gemelli IRCCS, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Rome, Italy; 5Università Cattolica del Sacro Cuore Rome, Istituto di Patologia e Semeiotica Medica, Rome, Italy; 6Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC Malattie Infettive, Rome, Italy; 7Istituto di Malattie Infettive, Università Cattolica del Sacro Cuore, Rome, Italy*These authors contributed equally to this workObjectives: To describe a rapid workflow based on the direct detection of Escherichia coli (Ec) and Klebsiella pneumoniae (Kp) producing CTX-M extended-spectrum β-lactamase (ESBL) and/or carbapenemases (eg, KPC, VIM) from blood cultures (BCs) and the infectious disease (ID) consulting for timely appropriate antimicrobial therapy.Methods: This observational, retrospective study included adult patients with a first episode of Ec or Kp bloodstream infection (BSI) in a large Italian university hospital, where an inpatient ID consultation team (IDCT) has been operational. Results from the BCs tested for detecting blaCTX-M, blaKPC, blaNDM, blaOXA-48-like, and blaVIM genes by the eazyplex®, SuperBug CRE assay in Ec and Kp organisms had been notified for antimicrobial therapy consulting.Results: In 321 BSI episodes studied, we found that 151 (47.0%) of Ec or Kp organisms harbored blaCTX-M and/or blaKPC and/or blaVIM (meantime from BC collection: 18.5 h). Empirical antimicrobial treatment was appropriate in 21.8% (33/151) of BSIs, namely 5.9% (3/51) of BSIs caused by KPC/VIM producers and 30.0% (30/100) of BSIs caused by CTX-M producers. After notification of results, the IDCT modified antimicrobial therapy (mean time from BC collection: 20 h) such that the proportion of appropriate treatments increased to 84.8% (128/151) of BSIs, namely 70.6% (36/51) of BSIs caused by KPC/VIM producers and 92.0% (92/100) of BSIs caused by CTX-M producers.Conclusion: Our study shows that a rapid diagnostic-driven clinical strategy allowed for early prescription of potentially effective antimicrobial therapy in BSIs caused by CTX-M ESBL- and/or KPC/VIM carbapenemase-producing Ec and Kp organisms.Keywords: Escherichia coli, Klebsiella pneumoniae, bloodstream infection, drug resistance, targeted therapy, infectious disease consultation

Published
2019

5. Magnetic and electronic transport percolation in epitaxial GeMn films

Author

Pinto, N., Morresi, L., Ficcadenti, M., Murri, R., D'Orazio, F., Lucari, F., Boarino, L., and Amato, G.

Subjects
Condensed Matter - Materials Science
Abstract

Electronic transport and magnetic properties of Ge1-xMnx/Ge(100) films are investigated as a function of Mn dilution. Depending on x, characteristic temperatures separate different regimes in both properties. Resistivity exhibits an insulator-like behavior in the whole temperature range and, below about 80 K, two distinct activation energies are observed. At a higher temperature value, TR, resistivity experiences a sudden reduction. Hall coefficient shows a strong contribution from the anomalous Hall effect and, at TR, a sign inversion, from positive to negative, is recorded. The magnetic properties, inferred from magneto-optical Kerr effect, evidence a progressive decrease of the ferromagnetic long range order as the temperature is raised, with a Curie temperature TC not far from TR. The transport and magnetic results are qualitatively consistent with a percolation mechanism due to bound magnetic polarons in a GeMn diluted magnetic semiconductor, with localized holes [A. Kaminski and S. Das Sarma, Phys. Rev. B 68, 235210 (2003)]., Comment: 16 pages, 6 figures. To be published in Phys. Rev. B

Published
2005
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6. Performance evaluation of the (1,3)-β-D-glucan detection assay in non-intensive care unit adult patients

Author

Murri R, Camici M, Posteraro B, Giovannenze F, Taccari F, Ventura G, Scoppettuolo G, Sanguinetti M, Cauda R, and Fantoni M

Subjects
beta-glucan, candidemia, Candida, bloodstream infections, antimicrobial stewardship, diagnostic biomarkers, Infectious and parasitic diseases, RC109-216
Abstract

Rita Murri,1 Marta Camici,1 Brunella Posteraro,2 Francesca Giovannenze,1 Francesco Taccari,1 Giulio Ventura,1 Giancarlo Scoppettuolo,1 Maurizio Sanguinetti,3 Roberto Cauda,1 Massimo Fantoni1 1Institute of Infectious Diseases, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy; 2Institute of Medical Pathology and Semeiotics, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy; 3Institute of Microbiology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy Objectives: To assess the performance of the (1,3)-β-D-glucan (BDG) detection assay in a large cohort of patients with suspected candidemia who were admitted to non-intensive care unit hospital wards. Methods: This observational, retrospective cohort study was conducted in a 1,100-bed university hospital in Rome, where an infectious disease consultation team has been operational. Two groups of patients were included in the analysis: Group 1, patients with Candida bloodstream infection (BSI) who had at least one BDG test performed ±48 hours from the first positive blood culture (Candida BSI Group) and Group 2, patients with risk factors for candidemia who had at least one BDG test but had negative blood cultures (Control Group). Both Group 1 and Group 2 did not receive prior antifungal therapy. Different BDG cutoff values were considered: 80, 200, 300, 400, and ≥500 pg/mL. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve were calculated. Results: A total of 1,296 patients were studied. Of them, 100 patients (candidemic) were in Group 1 and the remaining 1,196 patients (controls) were in Group 2. There were no differences in demographic characteristics between patients of the two groups. According to the above cutoff values, sensitivity (%) and specificity (%) of the BDG assay ranged from 91 to 60.7 and 87.7 to 97.8, respectively, whereas the PPV (%) and NPV (%) ranged from 38.2 to 68.3 and 99.1 to 97.0, respectively. Conclusion: Serum BDG has a very high NPV in a population with~10% prevalence of candidemia. This NPV may support decisions to discontinue antifungal therapy in those patients who were empirically treated because of the suspect of candidemia. Keywords: β-glucan, candidemia, Candida, bloodstream infections, antimicrobial stewardship, diagnostic biomarkers

Published
2018

7. EPI-Net One Health reporting guideline for antimicrobial consumption and resistance surveillance data: a Delphi approach

Author

Babu Rajendran, N., Arieti, F., Mena-Benitez, C. A., Galia, L., Tebon, M., Alvarez, J., Gladstone, B. P., Collineau, L., De Angelis, Giulia, Duro, R., Gaze, W., Gopel, S., Kanj, S. S., Kasbohrer, A., Limmathurotsakul, D., Lopez de Abechuco, E., Mazzolini, E., Mutters, N. T., Pezzani, M. D., Presterl, E., Renk, H., Rodriguez-Bano, J., Sandulescu, O., Scali, F., Skov, R., Velavan, T. P., Vuong, C., Tacconelli, Evelina, Adegnika, A. A., Avery, L., Bonten, M., Cassini, A., Chauvin, C., Compri, M., Damborg, P., De Greeff, S., Del Toro, M. D., Filter, M., Franklin, A., Gonzalez-Zorn, B., Grave, K., Hocquet, D., Hoelzle, L. E., Kalanxhi, E., Laxminarayan, R., Leibovici, L., Malhotra-Kumar, S., Mendelson, M., Paul, M., Munoz Madero, C., Murri, Rita, Piddock, L. J. V., Ruesen, C., Sanguinetti, Maurizio, Schilling, T., Schrijver, R., Schwaber, M. J., Scudeller, L., Torumkuney, D., Van Boeckel, T., Vanderhaeghen, W., Voss, A., Wozniak, T., De Angelis G. (ORCID:0000-0002-7087-7399), Tacconelli E. (ORCID:0000-0001-8722-5824), Murri R. (ORCID:0000-0003-4263-7854), Sanguinetti M. (ORCID:0000-0002-9780-7059), Babu Rajendran, N., Arieti, F., Mena-Benitez, C. A., Galia, L., Tebon, M., Alvarez, J., Gladstone, B. P., Collineau, L., De Angelis, Giulia, Duro, R., Gaze, W., Gopel, S., Kanj, S. S., Kasbohrer, A., Limmathurotsakul, D., Lopez de Abechuco, E., Mazzolini, E., Mutters, N. T., Pezzani, M. D., Presterl, E., Renk, H., Rodriguez-Bano, J., Sandulescu, O., Scali, F., Skov, R., Velavan, T. P., Vuong, C., Tacconelli, Evelina, Adegnika, A. A., Avery, L., Bonten, M., Cassini, A., Chauvin, C., Compri, M., Damborg, P., De Greeff, S., Del Toro, M. D., Filter, M., Franklin, A., Gonzalez-Zorn, B., Grave, K., Hocquet, D., Hoelzle, L. E., Kalanxhi, E., Laxminarayan, R., Leibovici, L., Malhotra-Kumar, S., Mendelson, M., Paul, M., Munoz Madero, C., Murri, Rita, Piddock, L. J. V., Ruesen, C., Sanguinetti, Maurizio, Schilling, T., Schrijver, R., Schwaber, M. J., Scudeller, L., Torumkuney, D., Van Boeckel, T., Vanderhaeghen, W., Voss, A., Wozniak, T., De Angelis G. (ORCID:0000-0002-7087-7399), Tacconelli E. (ORCID:0000-0001-8722-5824), Murri R. (ORCID:0000-0003-4263-7854), and Sanguinetti M. (ORCID:0000-0002-9780-7059)

Abstract

Strategic and standardised approaches to analysis and reporting of surveillance data are essential to inform antimicrobial resistance (AMR) mitigation measures, including antibiotic policies. Targeted guidance on linking full-scale AMR and antimicrobial consumption (AMC)/antimicrobial residues (AR) surveillance data from the human, animal, and environmental sectors is currently needed. This paper describes the initiative whereby a multidisciplinary panel of experts (56 from 20 countries—52 high income, 4 upper middle or lower income), representing all three sectors, elaborated proposals for structuring and reporting full-scale AMR and AMC/AR surveillance data across the three sectors. An evidence-supported, modified Delphi approach was adopted to reach consensus among the experts for dissemination frequency, language, and overall structure of reporting; core elements and metrics for AMC/AR data; core elements and metrics for AMR data. The recommendations can support multisectoral national and regional plans on antimicrobials policy to reduce resistance rates applying a One Health approach.

Published
2023

10. The role of early procalcitonin determination in the emergency department in adults hospitalized with fever

Author

Covino, M., Gallo, A., Montalto, M., De Matteis, G., Burzo, M. L., Simeoni, B., Murri, R., Candelli, M., Ojetti, V., Franceschi, F., Covino M. (ORCID:0000-0002-6709-2531), Gallo A., Montalto M. (ORCID:0000-0001-8819-3684), De Matteis G., Simeoni B., Murri R. (ORCID:0000-0003-4263-7854), Candelli M. (ORCID:0000-0001-8443-7880), Ojetti V. (ORCID:0000-0002-8953-0707), Franceschi F. (ORCID:0000-0001-6266-445X), Covino, M., Gallo, A., Montalto, M., De Matteis, G., Burzo, M. L., Simeoni, B., Murri, R., Candelli, M., Ojetti, V., Franceschi, F., Covino M. (ORCID:0000-0002-6709-2531), Gallo A., Montalto M. (ORCID:0000-0001-8819-3684), De Matteis G., Simeoni B., Murri R. (ORCID:0000-0003-4263-7854), Candelli M. (ORCID:0000-0001-8443-7880), Ojetti V. (ORCID:0000-0002-8953-0707), and Franceschi F. (ORCID:0000-0001-6266-445X)

Abstract

Background and Objectives: Fever is one of the most common presenting complaints in the Emergency Department (ED). The role of serum procalcitonin (PCT) determination in the ED evaluation of adults presenting with fever is still debated. The aim of this study was to evaluate if, in adults presenting to the ED with fever and then hospitalized, the early PCT determination could improve prognosis. Materials and Methods. This is a retrospective, mono-centric study, conducted over a 10-year period (2009–2018). We analyzed consecutive patients ≥18 years admitted to ED with fever and then hospitalized. According to quick sequential organ failure assessment (qSOFA) at admission, we compared patients that had a PCT determination vs. controls. Primary endpoint was overall inhospital mortality; secondary endpoints were in-hospital length of stay, and mortality in patients with bloodstream infection and acute respiratory infections. Results. The sample included 12,062 patients, median age was 71 years and 55.1% were men. In patients with qSOFA ≥ 2 overall mortality was significantly lower if they had a PCT-guided management in ED, (20.5% vs. 26.5%; p = 0.046). In the qSOFA > 2 group the mortality was not significantly different in PCT patients, except for those with a final diagnosis of bloodstream infection. Conclusions. Among adults hospitalized with fever, the PCT evaluation at ED admission was not associated with better outcomes, with the possible exception of patients affected by bloodstream infections. However, in febrile patients presenting to the ED with qSOFA ≥ 2, the early PCT evaluation could improve the overall in-hospital survival.

Published
2021

13. Cefiderocol for severe carbapenem-resistant a. Baumannii pneumonia: Towards the comprehension of its place in therapy

Author

Rando, Emanuele, Segala, F. V., Vargas, J., Seguiti, C., De Pascale, Gennaro, Murri, Rita, Fantoni, Massimo, Rando E., De Pascale G. (ORCID:0000-0002-8255-0676), Murri R. (ORCID:0000-0003-4263-7854), Fantoni M. (ORCID:0000-0001-6913-8460), Rando, Emanuele, Segala, F. V., Vargas, J., Seguiti, C., De Pascale, Gennaro, Murri, Rita, Fantoni, Massimo, Rando E., De Pascale G. (ORCID:0000-0002-8255-0676), Murri R. (ORCID:0000-0003-4263-7854), and Fantoni M. (ORCID:0000-0001-6913-8460)

Abstract

Cefiderocol use in A. baumannii pneumonia still represents an important matter of debate. The aim of this study is to describe 13 cases of carbapenem-resistant A. baumannii (CRAB) pneumonia treated with cefiderocol in real-life practice. We retrospectively included patients with CRAB pneumonia hospitalized at Fondazione Policlinico Universitario Agostino Gemelli Hospital treated with cefiderocol either in the general ward or the intensive care unit. A total of 11 patients out of 13 had ventilator-associated pneumonia caused by CRAB, and 12/13 patients had polymicrobial infection. We found a 30-day success rate of 54%. Cefiderocol may have a role when facing severe XDR A. baumannii pneumonia. Future studies are warranted to better define its place in therapy in CRAB infections.

Published
2022

14. Fatigue in Covid-19 survivors: The potential impact of a nutritional supplement on muscle strength and function

Author

Galluzzo, Vincenzo, Zazzara, Maria Beatrice, Ciciarello, Francesca, Savera, Giulia, Pais, C., Calvani, Riccardo, Picca, A., Marzetti, Emanuele, Landi, Francesco, Tosato, Matteo, Steering, Committee, Gremese, Elisa, Coordination, Bernabei, Roberto, Fantoni, Massimo, Gasbarrini, Antonio, Field, Investigator, Gastroenterology, Team, Porcari, Serena, Settanni, Carlo Romano, Geriatric, Team, Benvenuto, F., Bramato, Giulia, Brandi, Vincenzo, Carfi, A., Fabrizi, Sofia, Lo Monaco, Maria Rita, Martone, Anna Maria, Napolitano, C., Pagano, Francesco Cosimo, Rocchi, Sara, Rota, E., Salerno, Andrea Maria, Tritto, M., Catalano, Lucio, Damiano, Francesco Paolo, Rocconi, Alessandra, Galliani, Alessandro, Spaziani, G., Tupputi, Salvatore, Cocchi, Camilla, Pirone, Flavia, D'Ignazio, F., Cacciatore, Stefano, Infectious disease, Team, Cauda, Roberto, Tamburrini, Enrica, Borghetti, Alberto, Di Gianbenedetto, S., Murri, Rita, Cingolani, Antonella, Ventura, Giulio, Taddei, E., Moschese, D., Ciccullo, A., Dusina, A., Internal Medicine, Team, Stella, L., Addolorato, Giovanni, Franceschi, Francesco, Mingrone, Geltrude, Zocco, Maria Assunta, Microbiology, Team, Sanguinetti, Maurizio, Cattani Franchi, Paola, Marchetti, Simona, Posteraro, Brunella, Sali, M., Neurology, Team, Bizzarro, Alessandra, Lauria, Alessandra, Ophthalmology, Team, Rizzo, Stanislao, Savastano, Maria Cristina, Gambini, Gloria, Cozzupoli, G. M., Culiersi, Carola, Otolaryngology, Team, Passali, Giulio Cesare, Paludetti, Gaetano, Galli, Jacopo, Crudo, F., Di Cintio, G., Longobardi, Ylenia, Tricarico, Laura, Santantonio, M., Pediatric, Team, Buonsenso, Danilo, Valentini, Piero, Pata, D., Sinatti, Dario, De Rose, Cristina, Pneumology, Team, Richeldi, Luca, Lombardi, F., Calabrese, Anna Chiara, Leone, Paolo Maria, Calvello, M. R., Intini, Enrica, Montemurro, G., Psychiatric, Team, Sani, Gabriele, Janiri, Delfina, Simonetti, Alessio, Giuseppin, G., Molinaro, M., Odica, M., Radiology, Team, Natale, Luigi, Larici, Anna Rita, Marano, Riccardo, Rheumatology, Team, Paglionico, A., Petricca, Luca, Gigante, Lavinia, Natalello, G., Fedele, Anna Laura, Lizzio, Marco Maria, Tolusso, Barbara, Di Mario, Clara, Alivernini, Stefano, Vascular, Team, Santoliquido, Angelo, Santoro, L., Di Giorgio, A., Nesci, A., Popolla, Valentina, Galluzzo V., Zazzara M. B., Ciciarello F., Savera G., Calvani R. (ORCID:0000-0001-5472-2365), Marzetti E. (ORCID:0000-0001-9567-6983), Landi F. (ORCID:0000-0002-3472-1389), Tosato M., Gremese E. (ORCID:0000-0002-2248-1058), Bernabei R. (ORCID:0000-0002-9197-004X), Fantoni M. (ORCID:0000-0001-6913-8460), Gasbarrini A. (ORCID:0000-0002-7278-4823), Porcari S., Settanni C. R., Bramato G., Brandi V., Fabrizi S., Lo Monaco M. R. (ORCID:0000-0002-1457-7981), Martone A. M., Pagano F. C., Rocchi S., Salerno A., Catalano L., Damiano F. P., Rocconi A., Galliani A., Tupputi S., Cocchi C., Pirone F., Cacciatore S., Cauda R. (ORCID:0000-0002-1498-4229), Tamburrini E. (ORCID:0000-0003-4930-426X), Borghetti A., Murri R. (ORCID:0000-0003-4263-7854), Cingolani A. (ORCID:0000-0002-3793-2755), Ventura G. (ORCID:0000-0002-0304-7264), Addolorato G. (ORCID:0000-0002-1522-9946), Franceschi F. (ORCID:0000-0001-6266-445X), Mingrone G. (ORCID:0000-0003-2021-528X), Zocco M. A. (ORCID:0000-0002-0814-9542), Sanguinetti M. (ORCID:0000-0002-9780-7059), Cattani P. (ORCID:0000-0003-4678-4763), Marchetti S., Posteraro B. (ORCID:0000-0002-1663-7546), Bizzarro A., Lauria A., Rizzo S. (ORCID:0000-0001-6302-063X), Savastano M. C. (ORCID:0000-0003-1397-4333), Gambini G., Culiersi C., Passali G. C. (ORCID:0000-0002-8176-0962), Paludetti G. (ORCID:0000-0003-2480-1243), Galli J. (ORCID:0000-0001-6353-6249), Longobardi Y., Tricarico L., Buonsenso D., Valentini P. (ORCID:0000-0001-6095-9510), Sinatti D., De Rose C., Richeldi L. (ORCID:0000-0001-8594-1448), Calabrese A., Leone P. M., Intini E., Sani G. (ORCID:0000-0002-9767-8752), Janiri D., Simonetti A., Natale L. (ORCID:0000-0002-7949-5119), Larici A. R. (ORCID:0000-0002-1882-6244), Marano R. (ORCID:0000-0003-2710-2093), Petricca L., Gigante L., Fedele A. L., Lizzio M. M., Tolusso B. (ORCID:0000-0002-9108-6609), Di Mario C., Alivernini S. (ORCID:0000-0002-7383-4212), Santoliquido A. (ORCID:0000-0003-1539-4017), Popolla V., Galluzzo, Vincenzo, Zazzara, Maria Beatrice, Ciciarello, Francesca, Savera, Giulia, Pais, C., Calvani, Riccardo, Picca, A., Marzetti, Emanuele, Landi, Francesco, Tosato, Matteo, Steering, Committee, Gremese, Elisa, Coordination, Bernabei, Roberto, Fantoni, Massimo, Gasbarrini, Antonio, Field, Investigator, Gastroenterology, Team, Porcari, Serena, Settanni, Carlo Romano, Geriatric, Team, Benvenuto, F., Bramato, Giulia, Brandi, Vincenzo, Carfi, A., Fabrizi, Sofia, Lo Monaco, Maria Rita, Martone, Anna Maria, Napolitano, C., Pagano, Francesco Cosimo, Rocchi, Sara, Rota, E., Salerno, Andrea Maria, Tritto, M., Catalano, Lucio, Damiano, Francesco Paolo, Rocconi, Alessandra, Galliani, Alessandro, Spaziani, G., Tupputi, Salvatore, Cocchi, Camilla, Pirone, Flavia, D'Ignazio, F., Cacciatore, Stefano, Infectious disease, Team, Cauda, Roberto, Tamburrini, Enrica, Borghetti, Alberto, Di Gianbenedetto, S., Murri, Rita, Cingolani, Antonella, Ventura, Giulio, Taddei, E., Moschese, D., Ciccullo, A., Dusina, A., Internal Medicine, Team, Stella, L., Addolorato, Giovanni, Franceschi, Francesco, Mingrone, Geltrude, Zocco, Maria Assunta, Microbiology, Team, Sanguinetti, Maurizio, Cattani Franchi, Paola, Marchetti, Simona, Posteraro, Brunella, Sali, M., Neurology, Team, Bizzarro, Alessandra, Lauria, Alessandra, Ophthalmology, Team, Rizzo, Stanislao, Savastano, Maria Cristina, Gambini, Gloria, Cozzupoli, G. M., Culiersi, Carola, Otolaryngology, Team, Passali, Giulio Cesare, Paludetti, Gaetano, Galli, Jacopo, Crudo, F., Di Cintio, G., Longobardi, Ylenia, Tricarico, Laura, Santantonio, M., Pediatric, Team, Buonsenso, Danilo, Valentini, Piero, Pata, D., Sinatti, Dario, De Rose, Cristina, Pneumology, Team, Richeldi, Luca, Lombardi, F., Calabrese, Anna Chiara, Leone, Paolo Maria, Calvello, M. R., Intini, Enrica, Montemurro, G., Psychiatric, Team, Sani, Gabriele, Janiri, Delfina, Simonetti, Alessio, Giuseppin, G., Molinaro, M., Odica, M., Radiology, Team, Natale, Luigi, Larici, Anna Rita, Marano, Riccardo, Rheumatology, Team, Paglionico, A., Petricca, Luca, Gigante, Lavinia, Natalello, G., Fedele, Anna Laura, Lizzio, Marco Maria, Tolusso, Barbara, Di Mario, Clara, Alivernini, Stefano, Vascular, Team, Santoliquido, Angelo, Santoro, L., Di Giorgio, A., Nesci, A., Popolla, Valentina, Galluzzo V., Zazzara M. B., Ciciarello F., Savera G., Calvani R. (ORCID:0000-0001-5472-2365), Marzetti E. (ORCID:0000-0001-9567-6983), Landi F. (ORCID:0000-0002-3472-1389), Tosato M., Gremese E. (ORCID:0000-0002-2248-1058), Bernabei R. (ORCID:0000-0002-9197-004X), Fantoni M. (ORCID:0000-0001-6913-8460), Gasbarrini A. (ORCID:0000-0002-7278-4823), Porcari S., Settanni C. R., Bramato G., Brandi V., Fabrizi S., Lo Monaco M. R. (ORCID:0000-0002-1457-7981), Martone A. M., Pagano F. C., Rocchi S., Salerno A., Catalano L., Damiano F. P., Rocconi A., Galliani A., Tupputi S., Cocchi C., Pirone F., Cacciatore S., Cauda R. (ORCID:0000-0002-1498-4229), Tamburrini E. (ORCID:0000-0003-4930-426X), Borghetti A., Murri R. (ORCID:0000-0003-4263-7854), Cingolani A. (ORCID:0000-0002-3793-2755), Ventura G. (ORCID:0000-0002-0304-7264), Addolorato G. (ORCID:0000-0002-1522-9946), Franceschi F. (ORCID:0000-0001-6266-445X), Mingrone G. (ORCID:0000-0003-2021-528X), Zocco M. A. (ORCID:0000-0002-0814-9542), Sanguinetti M. (ORCID:0000-0002-9780-7059), Cattani P. (ORCID:0000-0003-4678-4763), Marchetti S., Posteraro B. (ORCID:0000-0002-1663-7546), Bizzarro A., Lauria A., Rizzo S. (ORCID:0000-0001-6302-063X), Savastano M. C. (ORCID:0000-0003-1397-4333), Gambini G., Culiersi C., Passali G. C. (ORCID:0000-0002-8176-0962), Paludetti G. (ORCID:0000-0003-2480-1243), Galli J. (ORCID:0000-0001-6353-6249), Longobardi Y., Tricarico L., Buonsenso D., Valentini P. (ORCID:0000-0001-6095-9510), Sinatti D., De Rose C., Richeldi L. (ORCID:0000-0001-8594-1448), Calabrese A., Leone P. M., Intini E., Sani G. (ORCID:0000-0002-9767-8752), Janiri D., Simonetti A., Natale L. (ORCID:0000-0002-7949-5119), Larici A. R. (ORCID:0000-0002-1882-6244), Marano R. (ORCID:0000-0003-2710-2093), Petricca L., Gigante L., Fedele A. L., Lizzio M. M., Tolusso B. (ORCID:0000-0002-9108-6609), Di Mario C., Alivernini S. (ORCID:0000-0002-7383-4212), Santoliquido A. (ORCID:0000-0003-1539-4017), and Popolla V.

Abstract

Background: Fatigue with reduced tolerance to exercise is a common persistent long-lasting feature amongst COVID-19 survivors. The assessment of muscle function in this category of patients is often neglected.Aim.: To evaluate the potential impact of a daily supplementation based on amino acids, minerals, vi-tamins, and plant extracts (Apportal (R)) on muscle function, body composition, laboratory parameters and self-rated health in a small group of COVID-19 survivors affected by fatigue.Methods: Thirty participants were enrolled among patients affected by physical fatigue during or after acute COVID-19 and admitted to the post-COVID-19 outpatient service at Fondazione Policlinico Gemelli in Rome between 1st March 2021 and 30th April 2021. All participants were evaluated at first visit (t0) and at control visit (t1), after taking a daily sachet of Apportal (R) for 28 days. Muscle function was analyzed using hand grip strength test, exhaustion strength time and the number of repetitions at one -minute chair stand test. Body composition was assessed with bioelectrical impedance analysis (BIA). Laboratory parameters, including standard blood biochemistry and ferritin levels, were evaluated at the first visit and during the control visit. A quick evaluation of self-rated health, before COVID-19, at t0 and t1, was obtained through a visual analogue scale (VAS). Results: Participants aged 60 years and older were 13 (43%). Females represented the 70% of the study sample. Participants hospitalized for COVID-19 with low -flow oxygen supplementation represented the 43.3% of the study sample while 3.3% received noninvasive ventilation (NIV) or invasive ventilation. Hand grip strength improved from 26.3 Kg to 28.9 Kg (p < 0.05) at t1 as compared to t0. The mean time of strength exhaustion increased from 31.7 s (sec) at t0 to 47.5 s at t1 (p < 0.05). Participants performed a higher number of repetitions (28.3 vs. 22.0; p < 0.05) during the one-minute chair stand test at

Published
2022

15. A real-time integrated framework to support clinical decision making for covid-19 patients

Author

Murri, Rita, Masciocchi, Carlotta, Lenkowicz, Jacopo, Fantoni, Massimo, Damiani, Andrea, Marchetti, A., Sergi, P. D. A., Arcuri, Giovanni, Cesario, Alfredo, Patarnello, S., Antonelli, Massimo, Bellantone, Rocco Domenico Alfonso, Bernabei, Roberto, Boccia, Stefania, Calabresi, Paolo, Cambieri, Andrea, Cauda, Roberto, Colosimo, Cesare, Crea, Filippo, De Maria Marchiano, Ruggero, De Stefano, Valerio, Franceschi, Francesco, Gasbarrini, Antonio, Landolfi, Raffaele, Parolini, Ornella, Richeldi, Luca, Sanguinetti, Maurizio, Urbani, Andrea, Zega, Maurizio, Scambia, Giovanni, Valentini, Vincenzo, Murri R. (ORCID:0000-0003-4263-7854), Masciocchi C., Lenkowicz J., Fantoni M. (ORCID:0000-0001-6913-8460), Damiani A., Arcuri G., Cesario A. (ORCID:0000-0003-4687-0709), Antonelli M. (ORCID:0000-0003-3007-1670), Bellantone R. (ORCID:0000-0002-0844-3469), Bernabei R. (ORCID:0000-0002-9197-004X), Boccia S. (ORCID:0000-0002-1864-749X), Calabresi P. (ORCID:0000-0003-0326-5509), Cambieri A., Cauda R. (ORCID:0000-0002-1498-4229), Colosimo C. (ORCID:0000-0003-3800-3648), Crea F. (ORCID:0000-0001-9404-8846), De Maria R. (ORCID:0000-0003-2255-0583), De Stefano V. (ORCID:0000-0002-5178-5827), Franceschi F. (ORCID:0000-0001-6266-445X), Gasbarrini A. (ORCID:0000-0002-7278-4823), Landolfi R. (ORCID:0000-0002-7913-8576), Parolini O. (ORCID:0000-0002-5211-6430), Richeldi L. (ORCID:0000-0001-8594-1448), Sanguinetti M. (ORCID:0000-0002-9780-7059), Urbani A. (ORCID:0000-0001-9168-3174), Zega M. (ORCID:0000-0002-7821-2615), Scambia G. (ORCID:0000-0003-2758-1063), Valentini V. (ORCID:0000-0003-4637-6487), Murri, Rita, Masciocchi, Carlotta, Lenkowicz, Jacopo, Fantoni, Massimo, Damiani, Andrea, Marchetti, A., Sergi, P. D. A., Arcuri, Giovanni, Cesario, Alfredo, Patarnello, S., Antonelli, Massimo, Bellantone, Rocco Domenico Alfonso, Bernabei, Roberto, Boccia, Stefania, Calabresi, Paolo, Cambieri, Andrea, Cauda, Roberto, Colosimo, Cesare, Crea, Filippo, De Maria Marchiano, Ruggero, De Stefano, Valerio, Franceschi, Francesco, Gasbarrini, Antonio, Landolfi, Raffaele, Parolini, Ornella, Richeldi, Luca, Sanguinetti, Maurizio, Urbani, Andrea, Zega, Maurizio, Scambia, Giovanni, Valentini, Vincenzo, Murri R. (ORCID:0000-0003-4263-7854), Masciocchi C., Lenkowicz J., Fantoni M. (ORCID:0000-0001-6913-8460), Damiani A., Arcuri G., Cesario A. (ORCID:0000-0003-4687-0709), Antonelli M. (ORCID:0000-0003-3007-1670), Bellantone R. (ORCID:0000-0002-0844-3469), Bernabei R. (ORCID:0000-0002-9197-004X), Boccia S. (ORCID:0000-0002-1864-749X), Calabresi P. (ORCID:0000-0003-0326-5509), Cambieri A., Cauda R. (ORCID:0000-0002-1498-4229), Colosimo C. (ORCID:0000-0003-3800-3648), Crea F. (ORCID:0000-0001-9404-8846), De Maria R. (ORCID:0000-0003-2255-0583), De Stefano V. (ORCID:0000-0002-5178-5827), Franceschi F. (ORCID:0000-0001-6266-445X), Gasbarrini A. (ORCID:0000-0002-7278-4823), Landolfi R. (ORCID:0000-0002-7913-8576), Parolini O. (ORCID:0000-0002-5211-6430), Richeldi L. (ORCID:0000-0001-8594-1448), Sanguinetti M. (ORCID:0000-0002-9780-7059), Urbani A. (ORCID:0000-0001-9168-3174), Zega M. (ORCID:0000-0002-7821-2615), Scambia G. (ORCID:0000-0003-2758-1063), and Valentini V. (ORCID:0000-0003-4637-6487)

Abstract

Background: The COVID-19 pandemic affected healthcare systems worldwide. Predictive models developed by Artificial Intelligence (AI) and based on timely, centralized and standardized real world patient data could improve management of COVID-19 to achieve better clinical outcomes. The objectives of this manuscript are to describe the structure and technologies used to construct a COVID-19 Data Mart architecture and to present how a large hospital has tackled the challenge of supporting daily management of COVID-19 pandemic emergency, by creating a strong retrospective knowledge base, a real time environment and integrated information dashboard for daily practice and early identification of critical condition at patient level. This framework is also used as an informative, continuously enriched data lake, which is a base for several on-going predictive studies. Methods: The information technology framework for clinical practice and research was described. It was developed using SAS Institute software analytics tool and SAS® Vyia® environment and Open-Source environment R ® and Python ® for fast prototyping and modeling. The included variables and the source extraction procedures were presented. Results: The Data Mart covers a retrospective cohort of 5528 patients with SARS-CoV-2 infection. People who died were older, had more comorbidities, reported more frequently dyspnea at onset, had higher D-dimer, C-reactive protein and urea nitrogen. The dashboard was developed to support the management of COVID-19 patients at three levels: hospital, single ward and individual care level. Interpretation: The COVID-19 Data Mart based on integration of a large collection of clinical data and an AI-based integrated framework has been developed, based on a set of automated procedures for data mining and retrieval, transformation and integration, and has been embedded in the clinical practice to help managing daily care. Benefits from the availability of a Data Mart include the oppor

Published
2022

16. Characteristic of IgA and IgG antibody response to SARS-CoV-2 infection in an Italian referral COVID-19 Hospital

Author

Carnicelli, A., Fiori, B., Ricci, Rosalba, Piano, A., Bonadia, N., Taddei, Eleonora, Fantoni, Massimo, Murri, Rita, Cingolani, Antonella, Barillaro, Christian, Cutuli, S. L., Marchesini, Debora, Della Polla, D. A., Forte, E., Fuorlo, M., Di Maurizio, L., Amorini, Paola, Cattani, P., Franceschi, Francesco, Sanguinetti, Maurizio, Ricci R., Taddei E., Fantoni M. (ORCID:0000-0001-6913-8460), Murri R. (ORCID:0000-0003-4263-7854), Cingolani A. (ORCID:0000-0002-3793-2755), Barillaro C., Marchesini D., Amorini P., Franceschi F. (ORCID:0000-0001-6266-445X), Sanguinetti M. (ORCID:0000-0002-9780-7059), Carnicelli, A., Fiori, B., Ricci, Rosalba, Piano, A., Bonadia, N., Taddei, Eleonora, Fantoni, Massimo, Murri, Rita, Cingolani, Antonella, Barillaro, Christian, Cutuli, S. L., Marchesini, Debora, Della Polla, D. A., Forte, E., Fuorlo, M., Di Maurizio, L., Amorini, Paola, Cattani, P., Franceschi, Francesco, Sanguinetti, Maurizio, Ricci R., Taddei E., Fantoni M. (ORCID:0000-0001-6913-8460), Murri R. (ORCID:0000-0003-4263-7854), Cingolani A. (ORCID:0000-0002-3793-2755), Barillaro C., Marchesini D., Amorini P., Franceschi F. (ORCID:0000-0001-6266-445X), and Sanguinetti M. (ORCID:0000-0002-9780-7059)

Abstract

Introduction: Antibody response plays a fundamental role in the natural history of infectious disease. A better understanding of the immune response in patients with SARS-CoV-2 infection could be important for identifying patients at greater risk of developing a more severe form of disease and with a worse prognosis. Methods: We performed a cross-sectional analysis to determine the presence and the levels of both anti-SARS-CoV-2 IgG and IgA in a cohort of hospitalized patients with confirmed infection at different times in the natural history of the disease. Patients enrolled when admitted at the emergency department were prospectively followed up during hospital stay. Results: Overall, 131 patients were considered with a total of 237 samples processed. Cross-sectional analysis showed that seroconversion for IgA seems to occur between days 6 and 15, while IgG response seems to occur slightly later, peaking at day 20 after symptoms onset. Both IgA and IgG were maintained beyond 2 months. Severe patients showed a higher IgA response compared with mild patients when analyzing optical density (8.3 versus 5.6, p < 0.001). Prospective analysis conducted on 55 patients confirmed that IgA appear slightly earlier than IgG. After stratifying for the severity of disease, both the IgA and IgG responses were more vigorous in severe cases. Moreover, while IgG tended to stabilize, there was a relevant decline after the first month of IgA levels in mild cases. Conclusion: IgA and IgG antibody response is closely related, although seroconversion for IgA occurs earlier. Both IgA and IgG are maintained beyond 2 months. Severe patients showed a more vigorous IgA and IgG response. IgA levels seem to decline after 1 month since the onset of symptoms in mild cases. Our results should be interpreted with cautions due to several limitations in our study, mainly the small number of cases, lack of data on viral load and clinical setting.

Published
2022

20. Early procalcitonin determination in the emergency department and clinical outcome of community-acquired pneumonia in old and oldest old patients

Author

Covino, M, Piccioni, A, Bonadia, N, Onder, G, Sabia, L, Carbone, L, Candelli, M, Ojetti, V, Murri, R, Franceschi, F., Covino M (ORCID:0000-0002-6709-2531), Piccioni A, Onder G (ORCID:0000-0003-3400-4491), Sabia L, Carbone L, Candelli M (ORCID:0000-0001-8443-7880), Ojetti V (ORCID:0000-0002-8953-0707), Murri R (ORCID:0000-0003-4263-7854), Franceschi F. (ORCID:0000-0001-6266-445X), Covino, M, Piccioni, A, Bonadia, N, Onder, G, Sabia, L, Carbone, L, Candelli, M, Ojetti, V, Murri, R, Franceschi, F., Covino M (ORCID:0000-0002-6709-2531), Piccioni A, Onder G (ORCID:0000-0003-3400-4491), Sabia L, Carbone L, Candelli M (ORCID:0000-0001-8443-7880), Ojetti V (ORCID:0000-0002-8953-0707), Murri R (ORCID:0000-0003-4263-7854), and Franceschi F. (ORCID:0000-0001-6266-445X)

Abstract

We evaluated patients admitted through our ED for community-acquired pneumonia (CAP) to assess the relevance of an early procalcitonin (PCT) determination on patient's outcomes. Methods: We reviewed all patients admitted for CAP in a 10 years period (2008-2017). Patients were stratified according to age groups: (18-65 years; 65-84 years; and ≥85 years), CURB-65 score, need for ventilation, Sepsis-3 criteria at admission, enrollment period, blood culture in ED. In-hospital mortality rate and length of hospital stay (LOS) were compared between patients that had an early PCT determination in ED vs. patients admitted without. Results: Our study cohort consisted of 4056 CAP patients, age 76 [IQ range 64-84] years. We enrolled 1039 patients <65 years old, 2015 aged 65-84 years, and 1002 aged ≥85 years. Overall, the early PCT determination in ED was not associated to a reduced LOS (p=0.630), nor to a reduced mortality rate (p=0.134). However, in patients ≥ 85 years, the PCT determination in ED was associated with lower mortality in those with CURB-65 ≥ 2, and Charlson's score ≥ 2 (p=0.033 and p=0.002, respectively). Conclusions: Although an early PCT assessment in ED was not associated with better outcomes in term of LOS and mortality in patients with CAP, our findings suggest that it might be associated with reduced mortality in patients ≥ 85 years with severe CAP or high comorbidity.

Published
2020

21. Post-COVID-19 global health strategies: the need for an interdisciplinary approach

Author

Landi, F., Gremese, E., Bernabei, R., Fantoni, M., Gasbarrini, A., Settanni, C. R., Benvenuto, F., Bramato, G., Carfi, A., Ciciarello, F., LoMonaco, M. R., Martone, A. M., Marzetti, E., Napolitano, C., Pagano, F., Rocchi, S., Rota, E., Salerno, A., Tosato, M., Tritto, M., Calvani, R., Catalano, L., Picca, A., Savera, G., Tamburrini, E., Borghetti, A., Di Gianbenedetto, S., Murri, R., Cingolani, A., Ventura, G., Taddei, E., Moschese, D., Ciccullo, A., Stella, L., Addolorato, G., Franceschi, F., Mingrone, G., Zocco, M. A., Sanguinetti, M., Cattani, P., Marchetti, S., Bizzarro, A., Lauria, A., Rizzo, S., Savastano, M. C., Gambini, G., Cozzupoli, G. M., Culiersi, C., Passali, G. C., Paludetti, G., Galli, J., Crudo, F., Di Cintio, G., Longobardi, Y., Tricarico, L., Santantonio, M., Buonsenso, D., Valentini, P., Pata, D., Sinatti, D., De Rose, C., Richeldi, L., Lombardi, F., Calabrese, A., Sani, G., Janiri, D., Giuseppin, G., Molinaro, M., Modica, M., Natale, L., Larici, A. R., Marano, R., Paglionico, A., Petricca, L., Gigante, L., Natalello, G., Fedele, A. L., Lizzio, M. M., Santoliquido, A., Santoro, L., Nesci, A., Popolla, V., Landi F. (ORCID:0000-0002-3472-1389), Gremese E. (ORCID:0000-0002-2248-1058), Bernabei R. (ORCID:0000-0002-9197-004X), Fantoni M. (ORCID:0000-0001-6913-8460), Gasbarrini A. (ORCID:0000-0002-7278-4823), Settanni C. R., Benvenuto F., Bramato G., Ciciarello F., Martone A. M., Marzetti E. (ORCID:0000-0001-9567-6983), Pagano F., Rocchi S., Rota E., Salerno A., Tosato M., Tritto M., Calvani R. (ORCID:0000-0001-5472-2365), Savera G., Tamburrini E. (ORCID:0000-0003-4930-426X), Borghetti A., Murri R. (ORCID:0000-0003-4263-7854), Cingolani A. (ORCID:0000-0002-3793-2755), Ventura G. (ORCID:0000-0002-0304-7264), Taddei E., Stella L., Addolorato G. (ORCID:0000-0002-1522-9946), Franceschi F. (ORCID:0000-0001-6266-445X), Mingrone G. (ORCID:0000-0003-2021-528X), Zocco M. A. (ORCID:0000-0002-0814-9542), Sanguinetti M. (ORCID:0000-0002-9780-7059), Cattani P. (ORCID:0000-0003-4678-4763), Marchetti S., Bizzarro A., Lauria A., Rizzo S. (ORCID:0000-0001-6302-063X), Savastano M. C. (ORCID:0000-0003-1397-4333), Culiersi C., Passali G. C. (ORCID:0000-0002-8176-0962), Paludetti G. (ORCID:0000-0003-2480-1243), Galli J. (ORCID:0000-0001-6353-6249), Crudo F., Longobardi Y., Tricarico L., Santantonio M., Buonsenso D., Valentini P. (ORCID:0000-0001-6095-9510), Pata D., Sinatti D., De Rose C., Richeldi L. (ORCID:0000-0001-8594-1448), Lombardi F., Calabrese A., Sani G. (ORCID:0000-0002-9767-8752), Giuseppin G., Molinaro M., Modica M., Natale L. (ORCID:0000-0002-7949-5119), Larici A. R. (ORCID:0000-0002-1882-6244), Marano R. (ORCID:0000-0003-2710-2093), Gigante L., Natalello G., Lizzio M. M., Santoliquido A. (ORCID:0000-0003-1539-4017), Santoro L., Nesci A. (ORCID:0000-0001-9466-1755), Popolla V., Landi, F., Gremese, E., Bernabei, R., Fantoni, M., Gasbarrini, A., Settanni, C. R., Benvenuto, F., Bramato, G., Carfi, A., Ciciarello, F., LoMonaco, M. R., Martone, A. M., Marzetti, E., Napolitano, C., Pagano, F., Rocchi, S., Rota, E., Salerno, A., Tosato, M., Tritto, M., Calvani, R., Catalano, L., Picca, A., Savera, G., Tamburrini, E., Borghetti, A., Di Gianbenedetto, S., Murri, R., Cingolani, A., Ventura, G., Taddei, E., Moschese, D., Ciccullo, A., Stella, L., Addolorato, G., Franceschi, F., Mingrone, G., Zocco, M. A., Sanguinetti, M., Cattani, P., Marchetti, S., Bizzarro, A., Lauria, A., Rizzo, S., Savastano, M. C., Gambini, G., Cozzupoli, G. M., Culiersi, C., Passali, G. C., Paludetti, G., Galli, J., Crudo, F., Di Cintio, G., Longobardi, Y., Tricarico, L., Santantonio, M., Buonsenso, D., Valentini, P., Pata, D., Sinatti, D., De Rose, C., Richeldi, L., Lombardi, F., Calabrese, A., Sani, G., Janiri, D., Giuseppin, G., Molinaro, M., Modica, M., Natale, L., Larici, A. R., Marano, R., Paglionico, A., Petricca, L., Gigante, L., Natalello, G., Fedele, A. L., Lizzio, M. M., Santoliquido, A., Santoro, L., Nesci, A., Popolla, V., Landi F. (ORCID:0000-0002-3472-1389), Gremese E. (ORCID:0000-0002-2248-1058), Bernabei R. (ORCID:0000-0002-9197-004X), Fantoni M. (ORCID:0000-0001-6913-8460), Gasbarrini A. (ORCID:0000-0002-7278-4823), Settanni C. R., Benvenuto F., Bramato G., Ciciarello F., Martone A. M., Marzetti E. (ORCID:0000-0001-9567-6983), Pagano F., Rocchi S., Rota E., Salerno A., Tosato M., Tritto M., Calvani R. (ORCID:0000-0001-5472-2365), Savera G., Tamburrini E. (ORCID:0000-0003-4930-426X), Borghetti A., Murri R. (ORCID:0000-0003-4263-7854), Cingolani A. (ORCID:0000-0002-3793-2755), Ventura G. (ORCID:0000-0002-0304-7264), Taddei E., Stella L., Addolorato G. (ORCID:0000-0002-1522-9946), Franceschi F. (ORCID:0000-0001-6266-445X), Mingrone G. (ORCID:0000-0003-2021-528X), Zocco M. A. (ORCID:0000-0002-0814-9542), Sanguinetti M. (ORCID:0000-0002-9780-7059), Cattani P. (ORCID:0000-0003-4678-4763), Marchetti S., Bizzarro A., Lauria A., Rizzo S. (ORCID:0000-0001-6302-063X), Savastano M. C. (ORCID:0000-0003-1397-4333), Culiersi C., Passali G. C. (ORCID:0000-0002-8176-0962), Paludetti G. (ORCID:0000-0003-2480-1243), Galli J. (ORCID:0000-0001-6353-6249), Crudo F., Longobardi Y., Tricarico L., Santantonio M., Buonsenso D., Valentini P. (ORCID:0000-0001-6095-9510), Pata D., Sinatti D., De Rose C., Richeldi L. (ORCID:0000-0001-8594-1448), Lombardi F., Calabrese A., Sani G. (ORCID:0000-0002-9767-8752), Giuseppin G., Molinaro M., Modica M., Natale L. (ORCID:0000-0002-7949-5119), Larici A. R. (ORCID:0000-0002-1882-6244), Marano R. (ORCID:0000-0003-2710-2093), Gigante L., Natalello G., Lizzio M. M., Santoliquido A. (ORCID:0000-0003-1539-4017), Santoro L., Nesci A. (ORCID:0000-0001-9466-1755), and Popolla V.

Abstract

For survivors of severe COVID-19 disease, having defeated the virus is just the beginning of an uncharted recovery path. What follows after the acute phase of SARS-CoV-2 infection depends on the extension and severity of viral attacks in different cell types and organs. Despite the ridiculously large number of papers that have flooded scientific journals and preprint-hosting websites, a clear clinical picture of COVID-19 aftermath is vague at best. Without larger prospective observational studies that are only now being started, clinicians can retrieve information just from case reports and or small studies. This is the time to understand how COVID-19 goes forward and what consequences survivors may expect to experience. To this aim, a multidisciplinary post-acute care service involving several specialists has been established at the Fondazione Policlinico Universitario A. Gemelli IRCSS (Rome, Italy). Although COVID-19 is an infectious disease primarily affecting the lung, its multi-organ involvement requires an interdisciplinary approach encompassing virtually all branches of internal medicine and geriatrics. In particular, during the post-acute phase, the geriatrician may serve as the case manager of a multidisciplinary team. The aim of this article is to describe the importance of the interdisciplinary approach––coordinated by geriatrician––to cope the potential post-acute care needs of recovered COVID-19 patients.

Published
2020

22. White Paper: Bridging the gap between surveillance data and antimicrobial stewardship in the outpatient sector-practical guidance from the JPIAMR ARCH and COMBACTE-MAGNET EPI-Net networks

Author

Arieti, F., Gopel, S., Sibani, M., Carrara, E., Pezzani, M. D., Murri, R., Mutters, N. T., Lopez-Cerero, L., Voss, A., Cauda, R., Tacconelli, E., Murri R. (ORCID:0000-0003-4263-7854), Cauda R. (ORCID:0000-0002-1498-4229), Tacconelli E. (ORCID:0000-0001-8722-5824), Arieti, F., Gopel, S., Sibani, M., Carrara, E., Pezzani, M. D., Murri, R., Mutters, N. T., Lopez-Cerero, L., Voss, A., Cauda, R., Tacconelli, E., Murri R. (ORCID:0000-0003-4263-7854), Cauda R. (ORCID:0000-0002-1498-4229), and Tacconelli E. (ORCID:0000-0001-8722-5824)

Abstract

BACKGROUND: The outpatient setting is a key scenario for the implementation of antimicrobial stewardship (AMS) activities, considering that overconsumption of antibiotics occurs mainly outside hospitals. This publication is the result of a joint initiative by the JPIAMR ARCH and COMBACTE-MAGNET EPI-Net networks, which is aimed at formulating a set of target actions for linking surveillance data with AMS activities in the outpatient setting. METHODS: A scoping review of the literature was carried out in three research areas: AMS leadership and accountability; antimicrobial usage and AMS; antimicrobial resistance and AMS. Consensus on the actions was reached through a RAND-modified Delphi process involving over 40 experts in infectious diseases, clinical microbiology, AMS, veterinary medicine or public health, from 18 low-, middle- and high-income countries. RESULTS: Evidence was retrieved from 38 documents, and an initial 25 target actions were proposed, differentiating between essential or desirable targets according to clinical relevance, feasibility and applicability to settings and resources. In the first consultation round, preliminary agreement was reached for all targets. Further to a second review, 6 statements were re-considered and 3 were deleted, leading to a final list of 22 target actions in the form of a practical checklist. CONCLUSIONS: This White Paper is a pragmatic and flexible tool to guide the development of calibrated surveillance-based AMS interventions specific to the outpatient setting, which is characterized by substantial inter- and intra-country variability in the organization of healthcare structures, maintaining a global perspective and taking into account the feasibility of the target actions in low-resource settings.

Published
2020

27. Seroprevalence of anti‐SARS‐CoV‐2 IgG antibodies in children with household exposure to adults with COVID‐19: Preliminary findings

Author

Buonsenso, Danilo, Valentini, Piero, De Rose, Cristina, Pata, Davide, Sinatti, Dario, Speziale, Domenico, Ricci, R., Carfi, A., Landi, Francesco, Ferrari, V., De Maio, Flavio, Palucci, Ivana, Sanguinetti, Maurizio, Sali, Michela, Landi, F., Gremese, E., Bernabei, R., Fantoni, M., Gasbarrini, A., Settanni, C. R., Benvenuto, F., Bramato, G., Ciciarello, F., Lo Monaco, M. R., Martone, A. M., Marzetti, Emanuele, Napolitano, C., Pagano, F., Rocchi, S., Rota, E., Salerno, A., Tosato, M., Tritto, M., Calvani, Riccardo, Catalano, L., Picca, A., Savera, G., Cauda, R., Tamburrini, E., Borghetti, A., Di Gianbenedetto, S., Murri, R., Cingolani, A., Ventura, G., Taddei, E., Moschese, D., Ciccullo, A., Stella, L., Addolorato, G., Franceschi, F., Mingrone, G., Zocco, Maria Assunta, Sanguinetti, M., Cattani Franchi, Paola, Marchetti, S., Posteraro, Brunella, Sali, M., Bizzarro, A., Lauria, A., Rizzo, S., Savastano, Maria Cristina, Gambini, G., Cozzupoli, G. M., Culiersi, C., Passali, G. C., Paludetti, G., Galli, J., Crudo, F., Di Cintio, G., Longobardi, Y., Tricarico, L., Santantonio, M., Buonsenso, D., Valentini, P., Pata, D., Sinatti, D., De Rose, C., Richeldi, Luca, Lombardi, F., Calabrese, A., Sani, G., Janiri, D., Giuseppin, G., Molinaro, M., Modica, M., Natale, Luigi, Larici, A. R., Marano, R., Paglionico, A., Petricca, L., Gigante, L., Natalello, G., Fedele, A. L., Lizzio, M. M., Tolusso, B., Alivernini, S., Santoliquido, A., Santoro, L., Nesci, A., and Popolla, V.

Subjects
Adult, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Adolescent, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Antibodies, Viral, Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA, Immunoglobulin G, SARS‐CoV‐2, 03 medical and health sciences, 0302 clinical medicine, children, COVID‐19, Seroepidemiologic Studies, 030225 pediatrics, Internal medicine, medicine, Seroprevalence, Humans, Pediatrics, Perinatology, and Child Health, Child, Index case, biology, seroprevalence, business.industry, SARS-CoV-2, Public health, Infant, Newborn, COVID-19, Infant, Environmental Exposure, Middle Aged, household, 030228 respiratory system, Child, Preschool, Pediatrics, Perinatology and Child Health, biology.protein, Commentary, Antibody, business, Pediatric population
Abstract

Weather and the susceptibility of children to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection is still a debated question and currently a hot topic, particularly in view of important decisions regarding opening schools. Therefore, we performed this prospective analysis of anti‐SARS‐CoV‐2 immunoglobulin G (IgG) antibodies in children with known household exposure to SARS‐CoV‐2 and compared their IgG status with the other adults exposed to the index case in the same household. A total of 30 families with a documented COVID‐19 index case were included. A total of 44 out of 80 household contacts (55%) of index patients had anti SARS‐CoV‐2 IgG antibodies. In particular, 16/27 (59,3%) adult partners had IgG antibodies compared with 28/53 (52,3%) of pediatric contacts (p > .05). Among the pediatric population, children ≥5 years of age had a similar probability of having SARS‐CoV‐2 IgG antibodies (21/39, 53.8%) compared to those less than 5 years old (7/14, 50%) (p > .05). Adult partners and children also had a similar probability of having SARS‐CoV‐2 IgG antibodies. Interestingly, 10/28 (35.7%) of children and 5/27 (18.5%) of adults with SARS‐CoV‐2 IgG antibodies were previously diagnosed as COVID‐19 cases. Our study shows evidence of a high rate of IgG antibodies in children exposed to SARS‐CoV‐2. This report has public health implications, highlighting the need to establish appropriate guidelines for school openings and other social activities related to childhood.

Published
2021
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29. Population pharmacokinetics and pharmacogenetics of ritonavir-boosted darunavir in the presence of raltegravir or tenofovir disoproxil fumarate/emtricitabine in HIV-infected adults and the relationship with virological response:a sub-study of the NEAT001/ANRS143 randomized trial

Author

Dickinson L., Gurjar R., Stohr W., Bonora S., Owen A., D'Avolio A., Cursley A., Molina J. -M., Faetkenheuer G., Vandekerckhove L., Di Perri G., Pozniak A., Richert L., Raffi F., Boffito M., Dedes N., Chene G., Allavena C., Autran B., Antinori A., Bucciardini R., Vella S., Horban A., Arribas J., Babiker A. G., Pillay D., Franquet X., Schwarze S., Grarup J., Fischer A., Wallet C., Diallo A., Saillard J., Moecklinghoff C., Stellbrink H. -J., Vanleeuwen R., Gatell J., Sandstrom E., Flepp M., Ewings F., George E. C., Hudson F., Pearce G., Quercia R., Rogatto F., Leavitt R., Nguyen B. -Y., Peto T., Goebel F., Marcotullio S., Miller V., Sasieni P., Arnault F., Boucherie C., Jean D., Paniego V., Paraina F., Rouch E., Schwimmer C., Soussi M., Taieb A., Termote M., Touzeau G., Babiker A., Dodds W., Hoppe A., Kummeling I., Pacciarini F., Paton N., Russell C., Taylor K., Ward D., Aagaard B., Eid M., Gey D., Gramjensen B., Jakobsen M. -L., Jansson P. O., Jensen K., Mariajoensen Z., Moseholmlarsen E., Pahl C., Pearson M., Nielsen B. R., Reilev So. S., Christ I., Lathouwers D., Manting C., Van Leeuwen R., Mendy B., Metro A., Couffin-Cadiergues S., Knellwolf A. -L., Palmisiano L., Aznar E., Barea C., Cotarelo M., Esteban H., Girbau I., Moyano B., Ramirez M., Saiz C., Sanchez I., Yllescas M., Binelli A., Colasanti V., Massella M., Anagnostou O., Gioukari V., Touloumi G., Schmied B., Rieger A., Vetter N., Dewit S., Florence E., Gerstoft J., Mathiesen L., Katlama C., Cabie A., Cheret A., Dupon M., Ghosn J., Girard P. -M., Goujard C., Levy Y., Morlat P., Neau D., Obadia M., Perre P., Piroth L., Reynes J., Tattevin P., Ragnaud J. M., Weiss L., Yazdan Y., Yeni P., Zucman D., Esser S., Fatkenheuer G., Hoffmann C., Jessen H., Rockstroh J., Schmidt R., Stephan C., Unger S., Hatzakis A., Daikos G. L., Papadopoulos A., Skoutelis A., Banhegyi D., Mallon P., Mulcahy F., Andreoni M., Castelli F., D'Arminiomonforte A., Diperri G., Galli M., Lazzarin A., Mazzotta F., Torti C., Vullo V., Prins J., Richter C., Verhagen D., Vaneeden A., Doroana M., Antunes F., Maltez F., Sarmento-Castro R., Gonzalez Garcia J., Aldeguer J. L., Clotet B., Domingo P., Gatell J. M., Knobel H., Marquez M., Pilarmiralles M., Portilla J., Soriano V., Tellez M., Thalme A., Blaxhult A., Gisslen M., Winston A., Fox J., Gompels M., Herieka E., Johnson M., Leen C., Teague A., Williams I., Boyd M., Moller N. F., Moseholmlarsen E. F., Lemoing V., Wit F. W. N. M., Kowalska J., Berenguer J., Moreno S., Muller N. J., Torok E., Post F., Angus B., Calvez V., Boucher C., Collins S., Dunn D., Lambert S., Marcelin A. -G., Perno C. F., White E., Ammassari A., Schmidt R. E., Odermarsky M., Smith C., Thiebaut R., Delaserna J. I. B., Castagna A., De Wit S., Furrer H. -J., Mocroft A., Reiss P., Fragola V., Lauriola M., Murri R., Nieuwkerk P., Spire B., Volny-Anne A., West B., Amieva H., Llibre Codina J., Braggion M., Foca E., Dickinson, L., Gurjar, R., Stohr, W., Bonora, S., Owen, A., D'Avolio, A., Cursley, A., Molina, J. -M., Faetkenheuer, G., Vandekerckhove, L., Di Perri, G., Pozniak, A., Richert, L., Raffi, F., Boffito, M., Dedes, N., Chene, G., Allavena, C., Autran, B., Antinori, A., Bucciardini, R., Vella, S., Horban, A., Arribas, J., Babiker, A. G., Pillay, D., Franquet, X., Schwarze, S., Grarup, J., Fischer, A., Wallet, C., Diallo, A., Saillard, J., Moecklinghoff, C., Stellbrink, H. -J., Vanleeuwen, R., Gatell, J., Sandstrom, E., Flepp, M., Ewings, F., George, E. C., Hudson, F., Pearce, G., Quercia, R., Rogatto, F., Leavitt, R., Nguyen, B. -Y., Peto, T., Goebel, F., Marcotullio, S., Miller, V., Sasieni, P., Arnault, F., Boucherie, C., Jean, D., Paniego, V., Paraina, F., Rouch, E., Schwimmer, C., Soussi, M., Taieb, A., Termote, M., Touzeau, G., Babiker, A., Dodds, W., Hoppe, A., Kummeling, I., Pacciarini, F., Paton, N., Russell, C., Taylor, K., Ward, D., Aagaard, B., Eid, M., Gey, D., Gramjensen, B., Jakobsen, M. -L., Jansson, P. O., Jensen, K., Mariajoensen, Z., Moseholmlarsen, E., Pahl, C., Pearson, M., Nielsen, B. R., Reilev, So. S., Christ, I., Lathouwers, D., Manting, C., Van Leeuwen, R., Mendy, B., Metro, A., Couffin-Cadiergues, S., Knellwolf, A. -L., Palmisiano, L., Aznar, E., Barea, C., Cotarelo, M., Esteban, H., Girbau, I., Moyano, B., Ramirez, M., Saiz, C., Sanchez, I., Yllescas, M., Binelli, A., Colasanti, V., Massella, M., Anagnostou, O., Gioukari, V., Touloumi, G., Schmied, B., Rieger, A., Vetter, N., Dewit, S., Florence, E., Gerstoft, J., Mathiesen, L., Katlama, C., Cabie, A., Cheret, A., Dupon, M., Ghosn, J., Girard, P. -M., Goujard, C., Levy, Y., Morlat, P., Neau, D., Obadia, M., Perre, P., Piroth, L., Reynes, J., Tattevin, P., Ragnaud, J. M., Weiss, L., Yazdan, Y., Yeni, P., Zucman, D., Esser, S., Fatkenheuer, G., Hoffmann, C., Jessen, H., Rockstroh, J., Schmidt, R., Stephan, C., Unger, S., Hatzakis, A., Daikos, G. L., Papadopoulos, A., Skoutelis, A., Banhegyi, D., Mallon, P., Mulcahy, F., Andreoni, M., Castelli, F., D'Arminiomonforte, A., Diperri, G., Galli, M., Lazzarin, A., Mazzotta, F., Torti, C., Vullo, V., Prins, J., Richter, C., Verhagen, D., Vaneeden, A., Doroana, M., Antunes, F., Maltez, F., Sarmento-Castro, R., Gonzalez Garcia, J., Aldeguer, J. L., Clotet, B., Domingo, P., Gatell, J. M., Knobel, H., Marquez, M., Pilarmiralles, M., Portilla, J., Soriano, V., Tellez, M., Thalme, A., Blaxhult, A., Gisslen, M., Winston, A., Fox, J., Gompels, M., Herieka, E., Johnson, M., Leen, C., Teague, A., Williams, I., Boyd, M., Moller, N. F., Moseholmlarsen, E. F., Lemoing, V., Wit, F. W. N. M., Kowalska, J., Berenguer, J., Moreno, S., Muller, N. J., Torok, E., Post, F., Angus, B., Calvez, V., Boucher, C., Collins, S., Dunn, D., Lambert, S., Marcelin, A. -G., Perno, C. F., White, E., Ammassari, A., Schmidt, R. E., Odermarsky, M., Smith, C., Thiebaut, R., Delaserna, J. I. B., Castagna, A., De Wit, S., Furrer, H. -J., Mocroft, A., Reiss, P., Fragola, V., Lauriola, M., Murri, R., Nieuwkerk, P., Spire, B., Volny-Anne, A., West, B., Amieva, H., Llibre Codina, J., Braggion, M., Foca, E., Infectious diseases, AII - Infectious diseases, APH - Aging & Later Life, Global Health, APH - Personalized Medicine, APH - Mental Health, and Medical Psychology

Subjects
0301 basic medicine, Microbiology (medical), Adult, Male, medicine.medical_specialty, Anti-HIV Agents, 030106 microbiology, HIV Infections, Emtricitabine, 030226 pharmacology & pharmacy, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, immune system diseases, Internal medicine, Raltegravir Potassium, medicine, Humans, Pharmacology (medical), Tenofovir, Darunavir, Constitutive Androstane Receptor, Pharmacology, Ritonavir, biology, business.industry, Liver-Specific Organic Anion Transporter 1, virus diseases, Lopinavir, Viral Load, Raltegravir, Multidrug Resistance-Associated Protein 2, 3. Good health, NONMEM, SISTM, Infectious Diseases, Pharmacogenetics, biology.protein, Female, SLCO1B1, business, medicine.drug
Abstract

Objectives NEAT001/ANRS143 demonstrated non-inferiority of once-daily darunavir/ritonavir (800/100 mg) + twice-daily raltegravir (400 mg) versus darunavir/ritonavir + tenofovir disoproxil fumarate/emtricitabine (245/200 mg once daily) in treatment-naive patients. We investigated the population pharmacokinetics of darunavir, ritonavir, tenofovir and emtricitabine and relationships with demographics, genetic polymorphisms and virological failure. Methods Non-linear mixed-effects models (NONMEM v. 7.3) were applied to determine pharmacokinetic parameters and assess demographic covariates and relationships with SNPs (SLCO3A1, SLCO1B1, NR1I2, NR1I3, CYP3A5*3, CYP3A4*22, ABCC2, ABCC10, ABCG2 and SCL47A1). The relationship between model-predicted darunavir AUC0–24 and C24 with time to virological failure was evaluated by Cox regression. Results Of 805 enrolled, 716, 720, 347 and 361 were included in the darunavir, ritonavir, tenofovir and emtricitabine models, respectively (11% female, 83% Caucasian). No significant effect of patient demographics or SNPs was observed for darunavir or tenofovir apparent oral clearance (CL/F); coadministration of raltegravir did not influence darunavir or ritonavir CL/F. Ritonavir CL/F decreased by 23% in NR1I2 63396C>T carriers and emtricitabine CL/F was linearly associated with creatinine clearance (P Conclusions Darunavir concentrations were unaltered in the presence of raltegravir and not associated with virological failure. Polymorphisms investigated had little impact on study-drug pharmacokinetics. Darunavir/ritonavir + raltegravir may be an appropriate option for patients experiencing NRTI-associated toxicity.

Published
2020
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31. Baricitinib as rescue therapy in a patient with COVID-19 with no complete response to sarilumab

Author

Cingolani, A., Tummolo, A. M., Montemurro, G., Gremese, E., Larosa, L., Cipriani, M. C., Pasciuto, G., Liperoti, R., Murri, R., Pirronti, T., Cauda, R., Fantoni, M., Bellieni, A., Brandi, V., Calabrese, A., Calvello, M. R., Ciccullo, A., Corbo, G., Falsiroli, C., Intini, E., Landi, G., Leone, P. M., Macagno, F., Martis, I., Pais, C., Potenza, A., Salini, S., Simonetti, J., Taddei, E., Tosato, M., Varone, F., Ventura, G., and Siciliano, M.

Subjects
0301 basic medicine, Male, Baricitinib, medicine.medical_treatment, Azithromycin, Lopinavir, 0302 clinical medicine, Respiratory function, 030212 general & internal medicine, Sulfonamides, Brief Report, General Medicine, Drug Combinations, Infectious Diseases, Treatment Outcome, Radiological weapon, Anesthesia, Acute Disease, Immunotherapy, Coronavirus Infections, Respiratory Insufficiency, medicine.drug, Hydroxychloroquine, Microbiology (medical), Coronavirus disease 2019 (COVID-19), 030106 microbiology, Pneumonia, Viral, Antibodies, Monoclonal, Humanized, Antiviral Agents, 03 medical and health sciences, Betacoronavirus, medicine, Humans, Pandemics, Aged, Ritonavir, business.industry, SARS-CoV-2, Sarilumab, Drug Repositioning, COVID-19, Respiratory failure, Purines, Azetidines, Pyrazoles, business
Abstract

A patient with COVID-19-related severe respiratory failure, with insufficient response to an antiretroviral therapy, hydroxychloroquine and Interleukin-6 (IL-6) antagonist therapy, presented a prompt resolution of the respiratory function and improvement in the radiological picture after baricitinib at an oral dose of 4 mg per day for 2 weeks.

Published
2020

32. COVID-19 and RA share an SPP1 myeloid pathway that drives PD-L1+ neutrophils and CD14+ monocytes

Author

MacDonald, L., Alivernini, S. (ORCID:0000-0002-7383-4212), Tolusso, B., Elmesmari, A., Somma, D., Perniola, S., Paglionico, A., Petricca, L., Bosello, S. L. (ORCID:0000-0002-4837-447X), Carfi, A., Sali, M., Stigliano, E., Cingolani, A. (ORCID:0000-0002-3793-2755), Murri, R. (ORCID:0000-0003-4263-7854), Arena, V. (ORCID:0000-0002-7562-223X), Fantoni, M., Antonelli, M. (ORCID:0000-0003-3007-1670), Landi, F. (ORCID:0000-0002-3472-1389), Franceschi, F., Sanguinetti, M. (ORCID:0000-0002-9780-7059), McInnes, I. B., McSharry, C., Gasbarrini, A. (ORCID:0000-0002-7278-4823), Otto, T. D., Kurowska-Stolarska, M., Gremese, E. (ORCID:0000-0002-2248-1058), MacDonald, L., Alivernini, S. (ORCID:0000-0002-7383-4212), Tolusso, B., Elmesmari, A., Somma, D., Perniola, S., Paglionico, A., Petricca, L., Bosello, S. L. (ORCID:0000-0002-4837-447X), Carfi, A., Sali, M., Stigliano, E., Cingolani, A. (ORCID:0000-0002-3793-2755), Murri, R. (ORCID:0000-0003-4263-7854), Arena, V. (ORCID:0000-0002-7562-223X), Fantoni, M., Antonelli, M. (ORCID:0000-0003-3007-1670), Landi, F. (ORCID:0000-0002-3472-1389), Franceschi, F., Sanguinetti, M. (ORCID:0000-0002-9780-7059), McInnes, I. B., McSharry, C., Gasbarrini, A. (ORCID:0000-0002-7278-4823), Otto, T. D., Kurowska-Stolarska, M., and Gremese, E. (ORCID:0000-0002-2248-1058)

Abstract

We explored the potential link between chronic inflammatory arthritis and COVID-19 pathogenic and resolving macrophage pathways and their role in COVID-19 pathogenesis. We found that bronchoalveolar lavage fluid (BALF) macrophage clusters FCN1+ and FCN1+SPP1+ predominant in severe COVID-19 were transcriptionally related to synovial tissue macrophage (STM) clusters CD48hiS100A12+ and CD48+SPP1+ that drive rheumatoid arthritis (RA) synovitis. BALF macrophage cluster FABP4+ predominant in healthy lung was transcriptionally related to STM cluster TREM2+ that governs resolution of synovitis in RA remission. Plasma concentrations of SPP1 and S100A12 (key products of macrophage clusters shared with active RA) were high in severe COVID-19 and predicted the need for Intensive Care Unit transfer, and they remained high in the post–COVID-19 stage. High plasma levels of SPP1 were unique to severe COVID-19 when compared with other causes of severe pneumonia, and IHC localized SPP1+ macrophages in the alveoli of COVID-19 lung. Investigation into SPP1 mechanisms of action revealed that it drives proinflammatory activation of CD14+ monocytes and development of PD-L1+ neutrophils, both hallmarks of severe COVID-19. In summary, COVID-19 pneumonitis appears driven by similar pathogenic myeloid cell pathways as those in RA, and their mediators such as SPP1 might be an upstream activator of the aberrant innate response in severe COVID-19 and predictive of disease trajectory including post–COVID-19 pathology.

Published
2021

33. Residual respiratory impairment after COVID-19 pneumonia

Author

Lombardi, F., Calabrese, Anna Chiara, Iovene, Bruno, Pierandrei, C., Lerede, M., Varone, Francesco, Richeldi, Luca, Sgalla, Giacomo, Landi, Francesco, Gremese, Elisa, Bernabei, Roberto, Fantoni, Massimo, Gasbarrini, Antonio, Romano Settanni, C., Benvenuto, F., Bramato, Giulia, Carfi, A., Ciciarello, Francesca, Lo Monaco, Maria Rita, Maria Martone, A., Marzetti, Emanuele, Napolitano, C., Pagano, Francesco Cosimo, Rocchi, Sara, Rota, E., Salerno, Andrea Maria, Tosato, Matteo, Tritto, M., Calvani, Riccardo, Catalano, Lucio, Picca, A., Savera, Giulia, Tamburrini, Enrica, Borghetti, Alberto, Di Gianbenedetto, S., Murri, Rita, Cingolani, Antonella, Ventura, Giulio, Taddei, E., Moschese, D., Ciccullo, A., Stella, L., Addolorato, Giovanni, Franceschi, Francesco, Mingrone, Geltrude, Assunta Zocco, M., Sanguinetti, Maurizio, Cattani Franchi, Paola, Marchetti, Simona, Bizzarro, Alessandra, Lauria, Alessandra, Rizzo, Stanislao, Cristina Savastano, M., Gambini, Gloria, Grazia Cozzupoli, M., Culiersi, Carola, Passali, Giulio Cesare, Paludetti, Gaetano, Galli, Jacopo, Crudo, F., Di Cintio, G., Longobardi, Ylenia, Tricarico, Laura, Santantonio, M., Buonsenso, Danilo, Valentini, Piero, Pata, D., Sinatti, Dario, De Rose, Cristina, Sani, Gabriele, Janiri, Delfina, Giuseppin, G., Molinaro, M., Modica, Marco, Natale, Luigi, Rita Larici, A., Marano, Riccardo, Paglionico, A., Petricca, Luca, Gigante, Lavinia, Natalello, G., Laur, a. Fedele A., Maria Lizzio, M., Santoliquido, Angelo, Santoro, L., Nesci, A., Popolla, Valentina, Calabrese A., Iovene B., Varone F., Richeldi L. (ORCID:0000-0001-8594-1448), Sgalla G. (ORCID:0000-0003-3130-9388), Landi F. (ORCID:0000-0002-3472-1389), Gremese E. (ORCID:0000-0002-2248-1058), Bernabei R. (ORCID:0000-0002-9197-004X), Fantoni M. (ORCID:0000-0001-6913-8460), Gasbarrini A. (ORCID:0000-0002-7278-4823), Bramato G., Ciciarello F., Lo Monaco M. R. (ORCID:0000-0002-1457-7981), Marzetti E. (ORCID:0000-0001-9567-6983), Pagano F., Rocchi S., Salerno A., Tosato M., Calvani R. (ORCID:0000-0001-5472-2365), Catalano L., Savera G., Tamburrini E. (ORCID:0000-0003-4930-426X), Borghetti A., Murri R. (ORCID:0000-0003-4263-7854), Cingolani A. (ORCID:0000-0002-3793-2755), Ventura G. (ORCID:0000-0002-0304-7264), Addolorato G. (ORCID:0000-0002-1522-9946), Franceschi F. (ORCID:0000-0001-6266-445X), Mingrone G. (ORCID:0000-0003-2021-528X), Sanguinetti M. (ORCID:0000-0002-9780-7059), Cattani P. (ORCID:0000-0003-4678-4763), Marchetti S., Bizzarro A., Lauria A., Rizzo S. (ORCID:0000-0001-6302-063X), Gambini G., Culiersi C., Cesare Passali G. (ORCID:0000-0002-8176-0962), Paludetti G. (ORCID:0000-0003-2480-1243), Galli J. (ORCID:0000-0001-6353-6249), Longobardi Y., Tricarico L., Buonsenso D., Valentini P. (ORCID:0000-0001-6095-9510), Sinatti D., De Rose C., Sani G. (ORCID:0000-0002-9767-8752), Janiri D., Modica M., Natale L. (ORCID:0000-0002-7949-5119), Marano R. (ORCID:0000-0003-2710-2093), Petricca L., Gigante L., Santoliquido A. (ORCID:0000-0003-1539-4017), Popolla V., Lombardi, F., Calabrese, Anna Chiara, Iovene, Bruno, Pierandrei, C., Lerede, M., Varone, Francesco, Richeldi, Luca, Sgalla, Giacomo, Landi, Francesco, Gremese, Elisa, Bernabei, Roberto, Fantoni, Massimo, Gasbarrini, Antonio, Romano Settanni, C., Benvenuto, F., Bramato, Giulia, Carfi, A., Ciciarello, Francesca, Lo Monaco, Maria Rita, Maria Martone, A., Marzetti, Emanuele, Napolitano, C., Pagano, Francesco Cosimo, Rocchi, Sara, Rota, E., Salerno, Andrea Maria, Tosato, Matteo, Tritto, M., Calvani, Riccardo, Catalano, Lucio, Picca, A., Savera, Giulia, Tamburrini, Enrica, Borghetti, Alberto, Di Gianbenedetto, S., Murri, Rita, Cingolani, Antonella, Ventura, Giulio, Taddei, E., Moschese, D., Ciccullo, A., Stella, L., Addolorato, Giovanni, Franceschi, Francesco, Mingrone, Geltrude, Assunta Zocco, M., Sanguinetti, Maurizio, Cattani Franchi, Paola, Marchetti, Simona, Bizzarro, Alessandra, Lauria, Alessandra, Rizzo, Stanislao, Cristina Savastano, M., Gambini, Gloria, Grazia Cozzupoli, M., Culiersi, Carola, Passali, Giulio Cesare, Paludetti, Gaetano, Galli, Jacopo, Crudo, F., Di Cintio, G., Longobardi, Ylenia, Tricarico, Laura, Santantonio, M., Buonsenso, Danilo, Valentini, Piero, Pata, D., Sinatti, Dario, De Rose, Cristina, Sani, Gabriele, Janiri, Delfina, Giuseppin, G., Molinaro, M., Modica, Marco, Natale, Luigi, Rita Larici, A., Marano, Riccardo, Paglionico, A., Petricca, Luca, Gigante, Lavinia, Natalello, G., Laur, a. Fedele A., Maria Lizzio, M., Santoliquido, Angelo, Santoro, L., Nesci, A., Popolla, Valentina, Calabrese A., Iovene B., Varone F., Richeldi L. (ORCID:0000-0001-8594-1448), Sgalla G. (ORCID:0000-0003-3130-9388), Landi F. (ORCID:0000-0002-3472-1389), Gremese E. (ORCID:0000-0002-2248-1058), Bernabei R. (ORCID:0000-0002-9197-004X), Fantoni M. (ORCID:0000-0001-6913-8460), Gasbarrini A. (ORCID:0000-0002-7278-4823), Bramato G., Ciciarello F., Lo Monaco M. R. (ORCID:0000-0002-1457-7981), Marzetti E. (ORCID:0000-0001-9567-6983), Pagano F., Rocchi S., Salerno A., Tosato M., Calvani R. (ORCID:0000-0001-5472-2365), Catalano L., Savera G., Tamburrini E. (ORCID:0000-0003-4930-426X), Borghetti A., Murri R. (ORCID:0000-0003-4263-7854), Cingolani A. (ORCID:0000-0002-3793-2755), Ventura G. (ORCID:0000-0002-0304-7264), Addolorato G. (ORCID:0000-0002-1522-9946), Franceschi F. (ORCID:0000-0001-6266-445X), Mingrone G. (ORCID:0000-0003-2021-528X), Sanguinetti M. (ORCID:0000-0002-9780-7059), Cattani P. (ORCID:0000-0003-4678-4763), Marchetti S., Bizzarro A., Lauria A., Rizzo S. (ORCID:0000-0001-6302-063X), Gambini G., Culiersi C., Cesare Passali G. (ORCID:0000-0002-8176-0962), Paludetti G. (ORCID:0000-0003-2480-1243), Galli J. (ORCID:0000-0001-6353-6249), Longobardi Y., Tricarico L., Buonsenso D., Valentini P. (ORCID:0000-0001-6095-9510), Sinatti D., De Rose C., Sani G. (ORCID:0000-0002-9767-8752), Janiri D., Modica M., Natale L. (ORCID:0000-0002-7949-5119), Marano R. (ORCID:0000-0003-2710-2093), Petricca L., Gigante L., Santoliquido A. (ORCID:0000-0003-1539-4017), and Popolla V.

Abstract

Introduction: The novel coronavirus SARS-Cov-2 can infect the respiratory tract causing a spectrum of disease varying from mild to fatal pneumonia, and known as COVID-19. Ongoing clinical research is assessing the potential for long-term respiratory sequelae in these patients. We assessed the respiratory function in a cohort of patients after recovering from SARS-Cov-2 infection, stratified according to PaO2/FiO2 (p/F) values. Method: Approximately one month after hospital discharge, 86 COVID-19 patients underwent physical examination, arterial blood gas (ABG) analysis, pulmonary function tests (PFTs), and six-minute walk test (6MWT). Patients were also asked to quantify the severity of dyspnoea and cough before, during, and after hospitalization using a visual analogic scale (VAS). Seventy-six subjects with ABG during hospitalization were stratified in three groups according to their worst p/F values: above 300 (n = 38), between 200 and 300 (n = 30) and below 200 (n = 20). Results: On PFTs, lung volumes were overall preserved yet, mean percent predicted residual volume was slightly reduced (74.8 ± 18.1%). Percent predicted diffusing capacity for carbon monoxide (DLCO) was also mildly reduced (77.2 ± 16.5%). Patients reported residual breathlessness at the time of the visit (VAS 19.8, p < 0.001). Patients with p/F below 200 during hospitalization had lower percent predicted forced vital capacity (p = 0.005), lower percent predicted total lung capacity (p = 0.012), lower DLCO (p < 0.001) and shorter 6MWT distance (p = 0.004) than patients with higher p/F. Conclusion: Approximately one month after hospital discharge, patients with COVID-19 can have residual respiratory impairment, including lower exercise tolerance. The extent of this impairment seems to correlate with the severity of respiratory failure during hospitalization.

Published
2021

34. Gemelli decision tree Algorithm to Predict the need for home monitoring or hospitalization of confirmed and unconfirmed COVID-19 patients (GAP-Covid19): preliminary results from a retrospective cohort study

Author

Vetrugno, Giuseppe, Laurenti, Patrizia, Franceschi, F, Foti, F, D'Ambrosio, F, Cicconi, M, La Milia, Daniele Ignazio, Di Pumpo, M, Carini, E, Pascucci, Domenico, Boccia, Stefania, Pastorino, Roberta, Damiani, Gianfranco, De-Giorgio, F, Oliva, A, Nicolotti, Nicola, Cambieri, Andrea, Ghisellini, R, Murri, Rita, Sabatelli, G, Musolino, M, Gasbarrini, Antonio, Vetrugno, G (ORCID:0000-0003-0181-2855), Laurenti, P (ORCID:0000-0002-8532-0593), LA Milia, D I, Pascucci, D (ORCID:0000-0002-5804-2284), Boccia, S (ORCID:0000-0002-1864-749X), Pastorino, R (ORCID:0000-0001-5013-0733), Damiani, G (ORCID:0000-0003-3028-6188), Nicolotti, N, Cambieri, A, Murri, R (ORCID:0000-0003-4263-7854), Gasbarrini, A (ORCID:0000-0002-7278-4823), Vetrugno, Giuseppe, Laurenti, Patrizia, Franceschi, F, Foti, F, D'Ambrosio, F, Cicconi, M, La Milia, Daniele Ignazio, Di Pumpo, M, Carini, E, Pascucci, Domenico, Boccia, Stefania, Pastorino, Roberta, Damiani, Gianfranco, De-Giorgio, F, Oliva, A, Nicolotti, Nicola, Cambieri, Andrea, Ghisellini, R, Murri, Rita, Sabatelli, G, Musolino, M, Gasbarrini, Antonio, Vetrugno, G (ORCID:0000-0003-0181-2855), Laurenti, P (ORCID:0000-0002-8532-0593), LA Milia, D I, Pascucci, D (ORCID:0000-0002-5804-2284), Boccia, S (ORCID:0000-0002-1864-749X), Pastorino, R (ORCID:0000-0001-5013-0733), Damiani, G (ORCID:0000-0003-3028-6188), Nicolotti, N, Cambieri, A, Murri, R (ORCID:0000-0003-4263-7854), and Gasbarrini, A (ORCID:0000-0002-7278-4823)

Abstract

OBJECTIVE: To develop a deep learning-based decision tree for the primary care setting, to stratify adult patients with confirmed and unconfirmed coronavirus disease 2019 (COVID-19), and to predict the need for hospitalization or home monitoring.PATIENTS AND METHODS: We performed a retrospective cohort study on data from patients admitted to a COVID hospital in Rome, Italy, between 5 March 2020 and 5 June 2020. A confirmed case was defined as a patient with a positive nasopharyngeal RT-PCR test result, while an unconfirmed case had negative results on repeated swabs. Patients' medical history and clinical, laboratory and radiological findings were collected, and the dataset was used to train a predictive model for COVID-19 severity.RESULTS: Data of 198 patients were included in the study. Twenty-eight (14.14%) had mild disease, 62 (31.31%) had moderate disease, 64 (32.32%) had severe disease, and 44 (22.22%) had critical disease. The G(2) value assessed the contribution of each collected value to decision tree building. On this basis, SpO2 (%) with a cut point at 92 was chosen for the optimal first split. Therefore, the decision tree was built using values maximizing G(2) and LogWorth. After the tree was built, the correspondence between inputs and outcomes was validated.CONCLUSIONS: We developed a machine learning-based tool that is easy to understand and apply. It provides good discrimination in stratifying confirmed and unconfirmed COVID-19 patients with different prognoses in every context. Our tool might allow general practitioners visiting patients at home to decide whether the patient needs to be hospitalized.

Published
2021

35. Post-prescription audit plus beta-d-glucan assessment decrease echinocandin use in people with suspected invasive candidiasis

Author

Murri, Rita, Lardo, S., De Luca, Alessio, Posteraro, Brunella, Torelli, Riccardo, De Angelis, Giulia, Giovannenze, Francesca, Taccari, Francesco, Pavan, L., Parroni, L., Sanguinetti, Maurizio, Fantoni, Massimo, Murri R. (ORCID:0000-0003-4263-7854), De Luca A., Posteraro B. (ORCID:0000-0002-1663-7546), Torelli R., De Angelis G. (ORCID:0000-0002-7087-7399), Giovannenze F., Taccari F., Sanguinetti M. (ORCID:0000-0002-9780-7059), Fantoni M. (ORCID:0000-0001-6913-8460), Murri, Rita, Lardo, S., De Luca, Alessio, Posteraro, Brunella, Torelli, Riccardo, De Angelis, Giulia, Giovannenze, Francesca, Taccari, Francesco, Pavan, L., Parroni, L., Sanguinetti, Maurizio, Fantoni, Massimo, Murri R. (ORCID:0000-0003-4263-7854), De Luca A., Posteraro B. (ORCID:0000-0002-1663-7546), Torelli R., De Angelis G. (ORCID:0000-0002-7087-7399), Giovannenze F., Taccari F., Sanguinetti M. (ORCID:0000-0002-9780-7059), and Fantoni M. (ORCID:0000-0001-6913-8460)

Abstract

Background and Objectives: Overtreatment with antifungal drugs is often observed. Antifungal stewardship (AFS) focuses on optimizing the treatment for invasive fungal diseases. The objective of the present study was to evaluate the utility of a post-prescription audit plus beta-D-glucan (BDG) assessment on reducing echinocandin use in persons with suspected invasive candidiasis. Materials and Methods: This is a prospective, pre-post quasi-experimental study of people starting echinocandins for suspected invasive candidiasis. The intervention of the study included review of each echinocandin prescription and discontinuation of treatment if a very low probability of fungal disease or a negative BDG value were found. Pre-intervention data were compared with the intervention phase. The primary outcome of the study was the duration of echinocandin therapy. Secondary outcomes were length of hospital stay and mortality. Results: Ninety-two echinocan-din prescriptions were reviewed, 49 (53.3%) in the pre-intervention phase and 43 (46.7%) in the intervention phase. Discontinuation of antifungal therapy was possible in 21 of the 43 patients in the intervention phase (48.8%). The duration of echinocandin therapy was 7.4 (SD 4.7) in the pre-intervention phase, 4.1 days (SD 2.9) in persons undergoing the intervention, and 8.6 (SD 7.3) in persons in whom the intervention was not feasible (p at ANOVA = 0.016). Length of stay and mortality did not differ between pre-intervention and intervention phases. Conclusions: An intervention based on pre-prescription restriction and post-prescription audit when combined with BDG measurement is effective in optimizing antifungal therapy by significantly reducing excessive treatment duration.

Published
2021

36. A machine-learning parsimonious multivariable predictive model of mortality risk in patients with Covid-19

Author

Murri, Rita, Lenkowicz, Jacopo, Masciocchi, Carlotta, Iacomini, C., Fantoni, Massimo, Damiani, Andrea, Marchetti, A., Sergi, P. D. A., Arcuri, G., Cesario, Alfredo, Patarnello, S., Antonelli, Massimo, Bellantone, Rocco Domenico Alfonso, Bernabei, Roberto, Boccia, Stefania, Calabresi, Paolo, Cambieri, Andrea, Cauda, Roberto, Colosimo, Cesare, Crea, Filippo, De Maria Marchiano, Ruggero, De Stefano, Valerio, Franceschi, Francesco, Gasbarrini, Antonio, Parolini, Ornella, Richeldi, Luca, Sanguinetti, Maurizio, Urbani, Andrea, Zega, Maurizio, Scambia, Giovanni, Valentini, Vincenzo, Armuzzi, Alessandro, Barba, Marta, Baroni, Silvia, Bellesi, Silvia, Bentivoglio, Anna Rita, Biasucci, Luigi Marzio, Biscetti, Federico, Candelli, Marcello, Capalbo, Gennaro, Cattani Franchi, Paola, Chiusolo, Patrizia, Cingolani, Antonella, Corbo, Giuseppe Maria, Covino, Marcello, Cozzolino, A. M., D'Alfonso, Maria Elena, De Angelis, Giulia, De Pascale, Gennaro, Frisullo, Giovanni, Gabrielli, M., Gambassi, Giovanni, Garcovich, M., Gremese, Elisa, Grieco, D. L., Iaconelli, A., Iorio, Raffaele, Landi, Francesco, Larici, Anna Rita, Liuzzo, Giovanna, Maviglia, Riccardo, Miele, Luca, Montalto, Massimo, Natale, Luigi, Nicolotti, Nicola, Ojetti, Veronica, Pompili, Maurizio, Posteraro, Brunella, Rapaccini, Gian Ludovico, Rinaldi, R., Rossi, Elena, Santoliquido, Angelo, Sica, Simona, Tamburrini, Enrica, Teofili, Luciana, Testa, Antonia Carla, Tosoni, A., Trani, Carlo, Varone, Francesco, Verme, L. Z. D., Murri R. (ORCID:0000-0003-4263-7854), Lenkowicz J., Masciocchi C., Fantoni M. (ORCID:0000-0001-6913-8460), Damiani A., Cesario A. (ORCID:0000-0003-4687-0709), Antonelli M. (ORCID:0000-0003-3007-1670), Bellantone R. (ORCID:0000-0002-0844-3469), Bernabei R. (ORCID:0000-0002-9197-004X), Boccia S. (ORCID:0000-0002-1864-749X), Calabresi P. (ORCID:0000-0003-0326-5509), Cambieri A., Cauda R. (ORCID:0000-0002-1498-4229), Colosimo C. (ORCID:0000-0003-3800-3648), Crea F. (ORCID:0000-0001-9404-8846), De Maria R. (ORCID:0000-0003-2255-0583), De Stefano V. (ORCID:0000-0002-5178-5827), Franceschi F. (ORCID:0000-0001-6266-445X), Gasbarrini A. (ORCID:0000-0002-7278-4823), Parolini O. (ORCID:0000-0002-5211-6430), Richeldi L. (ORCID:0000-0001-8594-1448), Sanguinetti M. (ORCID:0000-0002-9780-7059), Urbani A. (ORCID:0000-0001-9168-3174), Zega M. (ORCID:0000-0002-7821-2615), Scambia G. (ORCID:0000-0003-2758-1063), Valentini V. (ORCID:0000-0003-4637-6487), Armuzzi A. (ORCID:0000-0003-1572-0118), Barba M. (ORCID:0000-0001-6084-7666), Baroni S. (ORCID:0000-0002-3410-2617), Bellesi S., Bentivoglio A. (ORCID:0000-0002-9663-095X), Biasucci L. M. (ORCID:0000-0002-6921-6497), Biscetti F. (ORCID:0000-0001-7449-657X), Candelli M. (ORCID:0000-0001-8443-7880), Capalbo G., Cattani P. (ORCID:0000-0003-4678-4763), Chiusolo P. (ORCID:0000-0002-1355-1587), Cingolani A. (ORCID:0000-0002-3793-2755), Corbo G. (ORCID:0000-0002-8104-4659), Covino M. (ORCID:0000-0002-6709-2531), D'Alfonso M., De Angelis G. (ORCID:0000-0002-7087-7399), De Pascale G. (ORCID:0000-0002-8255-0676), Frisullo G., Gambassi G. (ORCID:0000-0002-7030-9359), Gremese E. (ORCID:0000-0002-2248-1058), Iorio R. (ORCID:0000-0002-6270-0956), Landi F. (ORCID:0000-0002-3472-1389), Larici A. (ORCID:0000-0002-1882-6244), Liuzzo G. (ORCID:0000-0002-5714-0907), Maviglia R., Miele L. (ORCID:0000-0003-3464-0068), Montalto M. (ORCID:0000-0001-8819-3684), Natale L. (ORCID:0000-0002-7949-5119), Nicolotti N., Ojetti V. (ORCID:0000-0002-8953-0707), Pompili M. (ORCID:0000-0001-6699-7980), Posteraro B. (ORCID:0000-0002-1663-7546), Rapaccini G. (ORCID:0000-0002-6467-857X), Rossi E. (ORCID:0000-0002-7572-9379), Santoliquido A. (ORCID:0000-0003-1539-4017), Sica S. (ORCID:0000-0003-2426-3465), Tamburrini E. (ORCID:0000-0003-4930-426X), Teofili L. (ORCID:0000-0002-7214-1561), Testa A. (ORCID:0000-0003-2217-8726), Trani C. (ORCID:0000-0001-9777-013X), Varone F., Murri, Rita, Lenkowicz, Jacopo, Masciocchi, Carlotta, Iacomini, C., Fantoni, Massimo, Damiani, Andrea, Marchetti, A., Sergi, P. D. A., Arcuri, G., Cesario, Alfredo, Patarnello, S., Antonelli, Massimo, Bellantone, Rocco Domenico Alfonso, Bernabei, Roberto, Boccia, Stefania, Calabresi, Paolo, Cambieri, Andrea, Cauda, Roberto, Colosimo, Cesare, Crea, Filippo, De Maria Marchiano, Ruggero, De Stefano, Valerio, Franceschi, Francesco, Gasbarrini, Antonio, Parolini, Ornella, Richeldi, Luca, Sanguinetti, Maurizio, Urbani, Andrea, Zega, Maurizio, Scambia, Giovanni, Valentini, Vincenzo, Armuzzi, Alessandro, Barba, Marta, Baroni, Silvia, Bellesi, Silvia, Bentivoglio, Anna Rita, Biasucci, Luigi Marzio, Biscetti, Federico, Candelli, Marcello, Capalbo, Gennaro, Cattani Franchi, Paola, Chiusolo, Patrizia, Cingolani, Antonella, Corbo, Giuseppe Maria, Covino, Marcello, Cozzolino, A. M., D'Alfonso, Maria Elena, De Angelis, Giulia, De Pascale, Gennaro, Frisullo, Giovanni, Gabrielli, M., Gambassi, Giovanni, Garcovich, M., Gremese, Elisa, Grieco, D. L., Iaconelli, A., Iorio, Raffaele, Landi, Francesco, Larici, Anna Rita, Liuzzo, Giovanna, Maviglia, Riccardo, Miele, Luca, Montalto, Massimo, Natale, Luigi, Nicolotti, Nicola, Ojetti, Veronica, Pompili, Maurizio, Posteraro, Brunella, Rapaccini, Gian Ludovico, Rinaldi, R., Rossi, Elena, Santoliquido, Angelo, Sica, Simona, Tamburrini, Enrica, Teofili, Luciana, Testa, Antonia Carla, Tosoni, A., Trani, Carlo, Varone, Francesco, Verme, L. Z. D., Murri R. (ORCID:0000-0003-4263-7854), Lenkowicz J., Masciocchi C., Fantoni M. (ORCID:0000-0001-6913-8460), Damiani A., Cesario A. (ORCID:0000-0003-4687-0709), Antonelli M. (ORCID:0000-0003-3007-1670), Bellantone R. (ORCID:0000-0002-0844-3469), Bernabei R. (ORCID:0000-0002-9197-004X), Boccia S. (ORCID:0000-0002-1864-749X), Calabresi P. (ORCID:0000-0003-0326-5509), Cambieri A., Cauda R. (ORCID:0000-0002-1498-4229), Colosimo C. (ORCID:0000-0003-3800-3648), Crea F. (ORCID:0000-0001-9404-8846), De Maria R. (ORCID:0000-0003-2255-0583), De Stefano V. (ORCID:0000-0002-5178-5827), Franceschi F. (ORCID:0000-0001-6266-445X), Gasbarrini A. (ORCID:0000-0002-7278-4823), Parolini O. (ORCID:0000-0002-5211-6430), Richeldi L. (ORCID:0000-0001-8594-1448), Sanguinetti M. (ORCID:0000-0002-9780-7059), Urbani A. (ORCID:0000-0001-9168-3174), Zega M. (ORCID:0000-0002-7821-2615), Scambia G. (ORCID:0000-0003-2758-1063), Valentini V. (ORCID:0000-0003-4637-6487), Armuzzi A. (ORCID:0000-0003-1572-0118), Barba M. (ORCID:0000-0001-6084-7666), Baroni S. (ORCID:0000-0002-3410-2617), Bellesi S., Bentivoglio A. (ORCID:0000-0002-9663-095X), Biasucci L. M. (ORCID:0000-0002-6921-6497), Biscetti F. (ORCID:0000-0001-7449-657X), Candelli M. (ORCID:0000-0001-8443-7880), Capalbo G., Cattani P. (ORCID:0000-0003-4678-4763), Chiusolo P. (ORCID:0000-0002-1355-1587), Cingolani A. (ORCID:0000-0002-3793-2755), Corbo G. (ORCID:0000-0002-8104-4659), Covino M. (ORCID:0000-0002-6709-2531), D'Alfonso M., De Angelis G. (ORCID:0000-0002-7087-7399), De Pascale G. (ORCID:0000-0002-8255-0676), Frisullo G., Gambassi G. (ORCID:0000-0002-7030-9359), Gremese E. (ORCID:0000-0002-2248-1058), Iorio R. (ORCID:0000-0002-6270-0956), Landi F. (ORCID:0000-0002-3472-1389), Larici A. (ORCID:0000-0002-1882-6244), Liuzzo G. (ORCID:0000-0002-5714-0907), Maviglia R., Miele L. (ORCID:0000-0003-3464-0068), Montalto M. (ORCID:0000-0001-8819-3684), Natale L. (ORCID:0000-0002-7949-5119), Nicolotti N., Ojetti V. (ORCID:0000-0002-8953-0707), Pompili M. (ORCID:0000-0001-6699-7980), Posteraro B. (ORCID:0000-0002-1663-7546), Rapaccini G. (ORCID:0000-0002-6467-857X), Rossi E. (ORCID:0000-0002-7572-9379), Santoliquido A. (ORCID:0000-0003-1539-4017), Sica S. (ORCID:0000-0003-2426-3465), Tamburrini E. (ORCID:0000-0003-4930-426X), Teofili L. (ORCID:0000-0002-7214-1561), Testa A. (ORCID:0000-0003-2217-8726), Trani C. (ORCID:0000-0001-9777-013X), and Varone F.

Abstract

The COVID-19 pandemic is impressively challenging the healthcare system. Several prognostic models have been validated but few of them are implemented in daily practice. The objective of the study was to validate a machine-learning risk prediction model using easy-to-obtain parameters to help to identify patients with COVID-19 who are at higher risk of death. The training cohort included all patients admitted to Fondazione Policlinico Gemelli with COVID-19 from March 5, 2020, to November 5, 2020. Afterward, the model was tested on all patients admitted to the same hospital with COVID-19 from November 6, 2020, to February 5, 2021. The primary outcome was in-hospital case-fatality risk. The out-of-sample performance of the model was estimated from the training set in terms of Area under the Receiving Operator Curve (AUROC) and classification matrix statistics by averaging the results of fivefold cross validation repeated 3-times and comparing the results with those obtained on the test set. An explanation analysis of the model, based on the SHapley Additive exPlanations (SHAP), is also presented. To assess the subsequent time evolution, the change in paO2/FiO2 (P/F) at 48 h after the baseline measurement was plotted against its baseline value. Among the 921 patients included in the training cohort, 120 died (13%). Variables selected for the model were age, platelet count, SpO2, blood urea nitrogen (BUN), hemoglobin, C-reactive protein, neutrophil count, and sodium. The results of the fivefold cross-validation repeated 3-times gave AUROC of 0.87, and statistics of the classification matrix to the Youden index as follows: sensitivity 0.840, specificity 0.774, negative predictive value 0.971. Then, the model was tested on a new population (n = 1463) in which the case-fatality rate was 22.6%. The test model showed AUROC 0.818, sensitivity 0.813, specificity 0.650, negative predictive value 0.922. Considering the first quartile of the predicted risk score (low-risk sc

Published
2021

38. Predictors of mortality among adult, old and the oldest old patients with bloodstream infections: An age comparison

Author

Giovannenze, F., Murri, Rita, Palazzolo, C., Taccari, F., Camici, M., Spanu, Teresa, Posteraro, Brunella, Sanguinetti, Maurizio, Cauda, Roberto, Onder, Graziano, Fantoni, Massimo, Murri R. (ORCID:0000-0003-4263-7854), Spanu T. (ORCID:0000-0003-1864-5184), Posteraro B. (ORCID:0000-0002-1663-7546), Sanguinetti M. (ORCID:0000-0002-9780-7059), Cauda R. (ORCID:0000-0002-1498-4229), Onder G. (ORCID:0000-0003-3400-4491), Fantoni M. (ORCID:0000-0001-6913-8460), Giovannenze, F., Murri, Rita, Palazzolo, C., Taccari, F., Camici, M., Spanu, Teresa, Posteraro, Brunella, Sanguinetti, Maurizio, Cauda, Roberto, Onder, Graziano, Fantoni, Massimo, Murri R. (ORCID:0000-0003-4263-7854), Spanu T. (ORCID:0000-0003-1864-5184), Posteraro B. (ORCID:0000-0002-1663-7546), Sanguinetti M. (ORCID:0000-0002-9780-7059), Cauda R. (ORCID:0000-0002-1498-4229), Onder G. (ORCID:0000-0003-3400-4491), and Fantoni M. (ORCID:0000-0001-6913-8460)

Abstract

Background: Bloodstream infections (BSIs) are a major cause of mortality in elderly. Objective of the study is to identify factors predictive of mortality in old and oldest old patients. Methods: This is a single centre retrospective observational study, including all patients admitted to Fondazione Policlinico A. Gemelli university hospital and diagnosed with BSI. Patients were stratified into three groups according to age: adult (A), younger than 65; old (O), aged between 65 and 80; oldest old (OO), older than 80. Primary outcome was 30-day in-hospital mortality. Secondary outcomes were duration of antimicrobial therapy (DOT) and length of hospital stay (LOS). Results: Of the 1034 patients included in the study, 346 were in group A, 447 in group O and 241 in group OO. The rate of 30-day mortality raised from 6.9% (24/346) in group A to 10.8% (84/447) in group O and 33.2% (80/241) in group OO (p<0.01), while DOT and LOS significantly decreased moving from adults to oldest old (p<0.01). Methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus spp were both independently correlated to an increased 30-day mortality risk selectively in patients older than 80 (MRSA: HR 2.37, p=0.03; Enterococcus spp: HR 2.44, p=0.01). Conclusions: BSIs have a high impact on survival in old and oldest old patients. BSIs by gram-positive pathogens, in particular MRSA and Enterococcus spp, should be a wake-up call for physicians, who should focus efforts on adequate and prompt antibiotic and support treatment.

Published
2021

46. Seroprevalence of anti-SARS-CoV-2 IgG antibodies in children with household exposure to adults with COVID-19: Preliminary findings

Author

Buonsenso, Danilo, Valentini, Piero, De Rose, Cristina, Pata, Davide, Sinatti, Dario, Speziale, Domenico, Ricci, R., Carfi, A., Landi, Francesco, Ferrari, V., De Maio, Flavio, Palucci, Ivana, Sanguinetti, Maurizio, Sali, Michela, Landi, F., Gremese, E., Bernabei, R., Fantoni, M., Gasbarrini, A., Settanni, C. R., Benvenuto, F., Bramato, G., Ciciarello, F., Lo Monaco, M. R., Martone, A. M., Marzetti, Emanuele, Napolitano, C., Pagano, F., Rocchi, S., Rota, E., Salerno, A., Tosato, M., Tritto, M., Calvani, Riccardo, Catalano, L., Picca, A., Savera, G., Cauda, R., Tamburrini, E., Borghetti, A., Di Gianbenedetto, S., Murri, R., Cingolani, A., Ventura, G., Taddei, E., Moschese, D., Ciccullo, A., Stella, L., Addolorato, G., Franceschi, F., Mingrone, G., Zocco, Maria Assunta, Sanguinetti, M., Cattani Franchi, Paola, Marchetti, S., Posteraro, Brunella, Sali, M., Bizzarro, A., Lauria, A., Rizzo, S., Savastano, Maria Cristina, Gambini, G., Cozzupoli, G. M., Culiersi, C., Passali, G. C., Paludetti, G., Galli, J., Crudo, F., Di Cintio, G., Longobardi, Y., Tricarico, L., Santantonio, M., Buonsenso, D., Valentini, P., Pata, D., Sinatti, D., De Rose, C., Richeldi, Luca, Lombardi, F., Calabrese, A., Sani, G., Janiri, D., Giuseppin, G., Molinaro, M., Modica, M., Natale, Luigi, Larici, A. R., Marano, R., Paglionico, A., Petricca, L., Gigante, L., Natalello, G., Fedele, A. L., Lizzio, M. M., Tolusso, B., Alivernini, S., Santoliquido, A., Santoro, L., Nesci, A., Popolla, V., Buonsenso D., Valentini P. (ORCID:0000-0001-6095-9510), De Rose C., Pata D., Sinatti D., Speziale D., Landi F. (ORCID:0000-0002-3472-1389), De Maio F., Palucci I., Sanguinetti M. (ORCID:0000-0002-9780-7059), Sali M. (ORCID:0000-0003-3609-2990), Marzetti E. (ORCID:0000-0001-9567-6983), Calvani R. (ORCID:0000-0001-5472-2365), Zocco M. A. (ORCID:0000-0002-0814-9542), Cattani P. (ORCID:0000-0003-4678-4763), Posteraro B. (ORCID:0000-0002-1663-7546), Savastano M. C. (ORCID:0000-0003-1397-4333), Richeldi L. (ORCID:0000-0001-8594-1448), Natale L. (ORCID:0000-0002-7949-5119), Buonsenso, Danilo, Valentini, Piero, De Rose, Cristina, Pata, Davide, Sinatti, Dario, Speziale, Domenico, Ricci, R., Carfi, A., Landi, Francesco, Ferrari, V., De Maio, Flavio, Palucci, Ivana, Sanguinetti, Maurizio, Sali, Michela, Landi, F., Gremese, E., Bernabei, R., Fantoni, M., Gasbarrini, A., Settanni, C. R., Benvenuto, F., Bramato, G., Ciciarello, F., Lo Monaco, M. R., Martone, A. M., Marzetti, Emanuele, Napolitano, C., Pagano, F., Rocchi, S., Rota, E., Salerno, A., Tosato, M., Tritto, M., Calvani, Riccardo, Catalano, L., Picca, A., Savera, G., Cauda, R., Tamburrini, E., Borghetti, A., Di Gianbenedetto, S., Murri, R., Cingolani, A., Ventura, G., Taddei, E., Moschese, D., Ciccullo, A., Stella, L., Addolorato, G., Franceschi, F., Mingrone, G., Zocco, Maria Assunta, Sanguinetti, M., Cattani Franchi, Paola, Marchetti, S., Posteraro, Brunella, Sali, M., Bizzarro, A., Lauria, A., Rizzo, S., Savastano, Maria Cristina, Gambini, G., Cozzupoli, G. M., Culiersi, C., Passali, G. C., Paludetti, G., Galli, J., Crudo, F., Di Cintio, G., Longobardi, Y., Tricarico, L., Santantonio, M., Buonsenso, D., Valentini, P., Pata, D., Sinatti, D., De Rose, C., Richeldi, Luca, Lombardi, F., Calabrese, A., Sani, G., Janiri, D., Giuseppin, G., Molinaro, M., Modica, M., Natale, Luigi, Larici, A. R., Marano, R., Paglionico, A., Petricca, L., Gigante, L., Natalello, G., Fedele, A. L., Lizzio, M. M., Tolusso, B., Alivernini, S., Santoliquido, A., Santoro, L., Nesci, A., Popolla, V., Buonsenso D., Valentini P. (ORCID:0000-0001-6095-9510), De Rose C., Pata D., Sinatti D., Speziale D., Landi F. (ORCID:0000-0002-3472-1389), De Maio F., Palucci I., Sanguinetti M. (ORCID:0000-0002-9780-7059), Sali M. (ORCID:0000-0003-3609-2990), Marzetti E. (ORCID:0000-0001-9567-6983), Calvani R. (ORCID:0000-0001-5472-2365), Zocco M. A. (ORCID:0000-0002-0814-9542), Cattani P. (ORCID:0000-0003-4678-4763), Posteraro B. (ORCID:0000-0002-1663-7546), Savastano M. C. (ORCID:0000-0003-1397-4333), Richeldi L. (ORCID:0000-0001-8594-1448), and Natale L. (ORCID:0000-0002-7949-5119)

Abstract

Weather and the susceptibility of children to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still a debated question and currently a hot topic, particularly in view of important decisions regarding opening schools. Therefore, we performed this prospective analysis of anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies in children with known household exposure to SARS-CoV-2 and compared their IgG status with the other adults exposed to the index case in the same household. A total of 30 families with a documented COVID-19 index case were included. A total of 44 out of 80 household contacts (55%) of index patients had anti SARS-CoV-2 IgG antibodies. In particular, 16/27 (59,3%) adult partners had IgG antibodies compared with 28/53 (52,3%) of pediatric contacts (p >.05). Among the pediatric population, children ≥5 years of age had a similar probability of having SARS-CoV-2 IgG antibodies (21/39, 53.8%) compared to those less than 5 years old (7/14, 50%) (p >.05). Adult partners and children also had a similar probability of having SARS-CoV-2 IgG antibodies. Interestingly, 10/28 (35.7%) of children and 5/27 (18.5%) of adults with SARS-CoV-2 IgG antibodies were previously diagnosed as COVID-19 cases. Our study shows evidence of a high rate of IgG antibodies in children exposed to SARS-CoV-2. This report has public health implications, highlighting the need to establish appropriate guidelines for school openings and other social activities related to childhood.

Published
2020

47. Post-COVID-19 global health strategies: the need for an interdisciplinary approach

Author

Landi, Francesco, Gremese, Elisa, Bernabei, Roberto, Fantoni, Massimo, Gasbarrini, Antonio, Settanni, Carlo Romano, Benvenuto, Francesca, Bramato, Giulia, Carfi, A., Ciciarello, Francesca, Lomonaco, M. R., Martone, Anna Maria, Marzetti, Emanuele, Napolitano, C., Pagano, Francesco Cosimo, Rocchi, Sara, Rota, Elisabetta, Salerno, A., Tosato, Matteo, Tritto, Marcello, Calvani, Riccardo, Catalano, Lucio, Picca, A., Savera, Giulia, Tamburrini, Enrica, Borghetti, Alberto, Di Gianbenedetto, S., Murri, Rita, Cingolani, Antonella, Ventura, Giulio, Taddei, Eleonora, Moschese, D., Ciccullo, A., Stella, L., Addolorato, Giovanni, Franceschi, Francesco, Mingrone, Geltrude, Zocco, Maria Assunta, Sanguinetti, Maurizio, Cattani Franchi, Paola, Marchetti, Simona, Bizzarro, Alessandra, Lauria, Alessandra, Rizzo, Stanislao, Savastano, Maria Cristina, Gambini, Gloria, Cozzupoli, G. M., Culiersi, Carola, Passali, Giulio Cesare, Paludetti, Gaetano, Galli, Jacopo, Crudo, Fabrizio, Di Cintio, G., Longobardi, Ylenia, Tricarico, Laura, Santantonio, Mariaconsiglia, Buonsenso, Danilo, Valentini, Piero, Pata, Davide, Sinatti, Dario, De Rose, Cristina, Richeldi, Luca, Lombardi, F., Calabrese, Anna Chiara, Sani, Gabriele, Janiri, D., Giuseppin, Giulia, Molinaro, Marzia, Modica, Marco, Natale, Luigi, Larici, Anna Rita, Marano, Riccardo, Paglionico, A., Petricca, L., Gigante, Laura, Natalello, Gerlando, Fedele, A. L., Lizzio, Marco Maria, Santoliquido, Angelo, Santoro, Luca, Nesci, Domenico Arturo, Popolla, Valentina, Landi F. (ORCID:0000-0002-3472-1389), Gremese E. (ORCID:0000-0002-2248-1058), Bernabei R. (ORCID:0000-0002-9197-004X), Fantoni M. (ORCID:0000-0001-6913-8460), Gasbarrini A. (ORCID:0000-0002-7278-4823), Settanni C. R., Benvenuto F., Bramato G., Ciciarello F., Martone A. M., Marzetti E. (ORCID:0000-0001-9567-6983), Pagano F., Rocchi S., Rota E., Tosato M., Tritto M., Calvani R. (ORCID:0000-0001-5472-2365), Catalano L., Savera G., Tamburrini E. (ORCID:0000-0003-4930-426X), Borghetti A., Murri R. (ORCID:0000-0003-4263-7854), Cingolani A. (ORCID:0000-0002-3793-2755), Ventura G. (ORCID:0000-0002-0304-7264), Taddei E., Addolorato G. (ORCID:0000-0002-1522-9946), Franceschi F. (ORCID:0000-0001-6266-445X), Mingrone G. (ORCID:0000-0003-2021-528X), Zocco M. A. (ORCID:0000-0002-0814-9542), Sanguinetti M. (ORCID:0000-0002-9780-7059), Cattani P. (ORCID:0000-0003-4678-4763), Marchetti S., Bizzarro A., Lauria A., Rizzo S. (ORCID:0000-0001-6302-063X), Savastano M. C. (ORCID:0000-0003-1397-4333), Gambini G., Culiersi C., Passali G. C. (ORCID:0000-0002-8176-0962), Paludetti G. (ORCID:0000-0003-2480-1243), Galli J. (ORCID:0000-0001-6353-6249), Crudo F., Longobardi Y., Tricarico L., Santantonio M., Buonsenso D., Valentini P. (ORCID:0000-0001-6095-9510), Pata D., Sinatti D., De Rose C., Richeldi L. (ORCID:0000-0001-8594-1448), Calabrese A., Sani G. (ORCID:0000-0002-9767-8752), Giuseppin G., Molinaro M., Modica M., Natale L. (ORCID:0000-0002-7949-5119), Larici A. R. (ORCID:0000-0002-1882-6244), Marano R. (ORCID:0000-0003-2710-2093), Gigante L., Natalello G., Lizzio M. M., Santoliquido A. (ORCID:0000-0003-1539-4017), Santoro L., Nesci A. (ORCID:0000-0001-9466-1755), Popolla V., Landi, Francesco, Gremese, Elisa, Bernabei, Roberto, Fantoni, Massimo, Gasbarrini, Antonio, Settanni, Carlo Romano, Benvenuto, Francesca, Bramato, Giulia, Carfi, A., Ciciarello, Francesca, Lomonaco, M. R., Martone, Anna Maria, Marzetti, Emanuele, Napolitano, C., Pagano, Francesco Cosimo, Rocchi, Sara, Rota, Elisabetta, Salerno, A., Tosato, Matteo, Tritto, Marcello, Calvani, Riccardo, Catalano, Lucio, Picca, A., Savera, Giulia, Tamburrini, Enrica, Borghetti, Alberto, Di Gianbenedetto, S., Murri, Rita, Cingolani, Antonella, Ventura, Giulio, Taddei, Eleonora, Moschese, D., Ciccullo, A., Stella, L., Addolorato, Giovanni, Franceschi, Francesco, Mingrone, Geltrude, Zocco, Maria Assunta, Sanguinetti, Maurizio, Cattani Franchi, Paola, Marchetti, Simona, Bizzarro, Alessandra, Lauria, Alessandra, Rizzo, Stanislao, Savastano, Maria Cristina, Gambini, Gloria, Cozzupoli, G. M., Culiersi, Carola, Passali, Giulio Cesare, Paludetti, Gaetano, Galli, Jacopo, Crudo, Fabrizio, Di Cintio, G., Longobardi, Ylenia, Tricarico, Laura, Santantonio, Mariaconsiglia, Buonsenso, Danilo, Valentini, Piero, Pata, Davide, Sinatti, Dario, De Rose, Cristina, Richeldi, Luca, Lombardi, F., Calabrese, Anna Chiara, Sani, Gabriele, Janiri, D., Giuseppin, Giulia, Molinaro, Marzia, Modica, Marco, Natale, Luigi, Larici, Anna Rita, Marano, Riccardo, Paglionico, A., Petricca, L., Gigante, Laura, Natalello, Gerlando, Fedele, A. L., Lizzio, Marco Maria, Santoliquido, Angelo, Santoro, Luca, Nesci, Domenico Arturo, Popolla, Valentina, Landi F. (ORCID:0000-0002-3472-1389), Gremese E. (ORCID:0000-0002-2248-1058), Bernabei R. (ORCID:0000-0002-9197-004X), Fantoni M. (ORCID:0000-0001-6913-8460), Gasbarrini A. (ORCID:0000-0002-7278-4823), Settanni C. R., Benvenuto F., Bramato G., Ciciarello F., Martone A. M., Marzetti E. (ORCID:0000-0001-9567-6983), Pagano F., Rocchi S., Rota E., Tosato M., Tritto M., Calvani R. (ORCID:0000-0001-5472-2365), Catalano L., Savera G., Tamburrini E. (ORCID:0000-0003-4930-426X), Borghetti A., Murri R. (ORCID:0000-0003-4263-7854), Cingolani A. (ORCID:0000-0002-3793-2755), Ventura G. (ORCID:0000-0002-0304-7264), Taddei E., Addolorato G. (ORCID:0000-0002-1522-9946), Franceschi F. (ORCID:0000-0001-6266-445X), Mingrone G. (ORCID:0000-0003-2021-528X), Zocco M. A. (ORCID:0000-0002-0814-9542), Sanguinetti M. (ORCID:0000-0002-9780-7059), Cattani P. (ORCID:0000-0003-4678-4763), Marchetti S., Bizzarro A., Lauria A., Rizzo S. (ORCID:0000-0001-6302-063X), Savastano M. C. (ORCID:0000-0003-1397-4333), Gambini G., Culiersi C., Passali G. C. (ORCID:0000-0002-8176-0962), Paludetti G. (ORCID:0000-0003-2480-1243), Galli J. (ORCID:0000-0001-6353-6249), Crudo F., Longobardi Y., Tricarico L., Santantonio M., Buonsenso D., Valentini P. (ORCID:0000-0001-6095-9510), Pata D., Sinatti D., De Rose C., Richeldi L. (ORCID:0000-0001-8594-1448), Calabrese A., Sani G. (ORCID:0000-0002-9767-8752), Giuseppin G., Molinaro M., Modica M., Natale L. (ORCID:0000-0002-7949-5119), Larici A. R. (ORCID:0000-0002-1882-6244), Marano R. (ORCID:0000-0003-2710-2093), Gigante L., Natalello G., Lizzio M. M., Santoliquido A. (ORCID:0000-0003-1539-4017), Santoro L., Nesci A. (ORCID:0000-0001-9466-1755), and Popolla V.

Abstract

For survivors of severe COVID-19 disease, having defeated the virus is just the beginning of an uncharted recovery path. What follows after the acute phase of SARS-CoV-2 infection depends on the extension and severity of viral attacks in different cell types and organs. Despite the ridiculously large number of papers that have flooded scientific journals and preprint-hosting websites, a clear clinical picture of COVID-19 aftermath is vague at best. Without larger prospective observational studies that are only now being started, clinicians can retrieve information just from case reports and or small studies. This is the time to understand how COVID-19 goes forward and what consequences survivors may expect to experience. To this aim, a multidisciplinary post-acute care service involving several specialists has been established at the Fondazione Policlinico Universitario A. Gemelli IRCSS (Rome, Italy). Although COVID-19 is an infectious disease primarily affecting the lung, its multi-organ involvement requires an interdisciplinary approach encompassing virtually all branches of internal medicine and geriatrics. In particular, during the post-acute phase, the geriatrician may serve as the case manager of a multidisciplinary team. The aim of this article is to describe the importance of the interdisciplinary approach––coordinated by geriatrician––to cope the potential post-acute care needs of recovered COVID-19 patients.

Published
2020

48. Increased CD95 (Fas) and PD-1 expression in peripheral blood T lymphocytes in COVID-19 patients

Author

Bellesi, Silvia, Metafuni, Elisabetta, Hohaus, Stefan, Maiolo, E., Marchionni, F., D'Innocenzo, S., La Sorda, M., Ferraironi, M., Ramundo, Francesco, Fantoni, M., Murri, Rita, Cingolani, Antonella, Sica, Simona, Gasbarrini, Antonio, Sanguinetti, Maurizio, Chiusolo, Patrizia, De Stefano, Valerio, Bellesi S., Metafuni E., Hohaus S. (ORCID:0000-0002-5534-7197), Ramundo F., Murri R. (ORCID:0000-0003-4263-7854), Cingolani A. (ORCID:0000-0002-3793-2755), Sica S. (ORCID:0000-0003-2426-3465), Gasbarrini A. (ORCID:0000-0002-7278-4823), Sanguinetti M. (ORCID:0000-0002-9780-7059), Chiusolo P. (ORCID:0000-0002-1355-1587), De Stefano V. (ORCID:0000-0002-5178-5827), Bellesi, Silvia, Metafuni, Elisabetta, Hohaus, Stefan, Maiolo, E., Marchionni, F., D'Innocenzo, S., La Sorda, M., Ferraironi, M., Ramundo, Francesco, Fantoni, M., Murri, Rita, Cingolani, Antonella, Sica, Simona, Gasbarrini, Antonio, Sanguinetti, Maurizio, Chiusolo, Patrizia, De Stefano, Valerio, Bellesi S., Metafuni E., Hohaus S. (ORCID:0000-0002-5534-7197), Ramundo F., Murri R. (ORCID:0000-0003-4263-7854), Cingolani A. (ORCID:0000-0002-3793-2755), Sica S. (ORCID:0000-0003-2426-3465), Gasbarrini A. (ORCID:0000-0002-7278-4823), Sanguinetti M. (ORCID:0000-0002-9780-7059), Chiusolo P. (ORCID:0000-0002-1355-1587), and De Stefano V. (ORCID:0000-0002-5178-5827)

Abstract

A low count of CD4+ and CD8+ lymphocytes is a hallmark laboratory finding in the coronavirus disease 2019 (COVID-19). Using flow cytometry, we observed significantly higher CD95 (Fas) and PD-1 expression on both CD4+ T and CD8+ T cells in 42 COVID-19 patients when compared to controls. Higher CD95 expression in CD4+ cells correlated with lower CD4+ counts. A higher expression of CD95 in CD4+ and CD8+ lymphocytes correlated with a lower percentage of naive events. Our results might suggest a shift to antigen-activated T cells, expressing molecules increasing their propensity to apoptosis and exhaustion during COVID-19 infection.

Published
2020

49. Antibiotic appropriateness and adherence to local guidelines in perioperative prophylaxis: results from an antimicrobial stewardship intervention

Author

Segala, Francesco Vladimiro, Murri, Rita, Taddei, Eleonora, Giovannenze, F., Del Vecchio, Pierluigi, Birocchi, E., Taccari, F., Cauda, Roberto, Fantoni, Massimo, Segala F. V., Murri R. (ORCID:0000-0003-4263-7854), Taddei E., Del Vecchio P., Cauda R. (ORCID:0000-0002-1498-4229), Fantoni M. (ORCID:0000-0001-6913-8460), Segala, Francesco Vladimiro, Murri, Rita, Taddei, Eleonora, Giovannenze, F., Del Vecchio, Pierluigi, Birocchi, E., Taccari, F., Cauda, Roberto, Fantoni, Massimo, Segala F. V., Murri R. (ORCID:0000-0003-4263-7854), Taddei E., Del Vecchio P., Cauda R. (ORCID:0000-0002-1498-4229), and Fantoni M. (ORCID:0000-0001-6913-8460)

Abstract

Objectives: Surgical antibiotic prophylaxis (SAP) represents a major indication of antibiotic consumption worldwide. The present study aims to report the results of an enabling, long-term AMS intervention conducted between 2013 and 2019 on an Italian University Hospital performing more than 40.000 surgical interventions per year. Methods: SAP inappropriateness was defined according to the ASHP guidelines and divided in four main categories: indication, selection and dosing, duration, timing. Between 2013 and 2019, we conducted a continuative AMS intervention over 14 surgical departments that included enablement, review of selected clinical records and feedback. Results: We collected a total of 789 SAP prescribed to 735 patients (mean age 56.7 ± 17.8y). Overall, guideline adherence improved from 36.6% (n = 149) at baseline to 57.9% (n = 221) post-intervention (P < 0.0001). A significant improvement (P < 0.001) was also detected for each category: indication (from 58.5 to 93.2%), selection and dosing (from 58.5 to 80.6%), timing (from 92.4 to 97.6%), duration (from 71 to 80.1%). Conclusions: Though results cannot be generalized to all hospital populations, enabling AMS interventions may be effective in establishing a sustained improvement in SAP appropriateness rates. Once identified the main causes of SAP inappropriateness, tailored AMS interventions for each department may be beneficial. Further studies are needed to evaluate specific outcomes as incidence of surgical site infections and antimicrobial resistance.

Published
2020

50. Sarilumab use in severe SARS-CoV-2 pneumonia

Author

Gremese, Elisa, Cingolani, Antonella, Bosello, Silvia Laura, Alivernini, Stefano, Tolusso, Barbara, Perniola, S., Landi, Francesco, Pompili, Maurizio, Murri, Rita, Santoliquido, Angelo, Garcovich, M., Sali, Michela, De Pascale, Gennaro, Gabrielli, Maurizio, Biscetti, Federico, Montalto, Massimo, Tosoni, Alessio, Gambassi, Giovanni, Rapaccini, Gian Ludovico, Iaconelli, Amerigo, Zileri Del Verme, L., Petricca, L., Fedele, A. L., Lizzio, Marco Maria, Tamburrini, Enrica, Natalello, Gerlando, Gigante, Laura, Bruno, D., Verardi, Lucrezia, Taddei, Eleonora, Calabrese, Anna Chiara, Lombardi, Francesca, Bernabei, Roberto, Cauda, Roberto, Franceschi, Francesco, Landolfi, Raffaele, Richeldi, Luca, Sanguinetti, Maurizio, Fantoni, Massimo, Antonelli, Massimo, Gasbarrini, Antonio, Gremese E. (ORCID:0000-0002-2248-1058), Cingolani A. (ORCID:0000-0002-3793-2755), Bosello S. L. (ORCID:0000-0002-4837-447X), Alivernini S. (ORCID:0000-0002-7383-4212), Tolusso B. (ORCID:0000-0002-9108-6609), Landi F. (ORCID:0000-0002-3472-1389), Pompili M. (ORCID:0000-0001-6699-7980), Murri R. (ORCID:0000-0003-4263-7854), Santoliquido A. (ORCID:0000-0003-1539-4017), Sali M. (ORCID:0000-0003-3609-2990), De Pascale G. (ORCID:0000-0002-8255-0676), Gabrielli M., Biscetti F. (ORCID:0000-0001-7449-657X), Montalto M. (ORCID:0000-0001-8819-3684), Tosoni A., Gambassi G. (ORCID:0000-0002-7030-9359), Rapaccini G. L. (ORCID:0000-0002-6467-857X), Iaconelli A., Lizzio M. M., Tamburrini E. (ORCID:0000-0003-4930-426X), Natalello G., Gigante L., Verardi L., Taddei E., Calabrese A., Lombardi F. (ORCID:0000-0001-5757-8346), Bernabei R. (ORCID:0000-0002-9197-004X), Cauda R. (ORCID:0000-0002-1498-4229), Franceschi F. (ORCID:0000-0001-6266-445X), Landolfi R. (ORCID:0000-0002-7913-8576), Richeldi L. (ORCID:0000-0001-8594-1448), Sanguinetti M. (ORCID:0000-0002-9780-7059), Fantoni M. (ORCID:0000-0001-6913-8460), Antonelli M. (ORCID:0000-0003-3007-1670), Gasbarrini A. (ORCID:0000-0002-7278-4823), Gremese, Elisa, Cingolani, Antonella, Bosello, Silvia Laura, Alivernini, Stefano, Tolusso, Barbara, Perniola, S., Landi, Francesco, Pompili, Maurizio, Murri, Rita, Santoliquido, Angelo, Garcovich, M., Sali, Michela, De Pascale, Gennaro, Gabrielli, Maurizio, Biscetti, Federico, Montalto, Massimo, Tosoni, Alessio, Gambassi, Giovanni, Rapaccini, Gian Ludovico, Iaconelli, Amerigo, Zileri Del Verme, L., Petricca, L., Fedele, A. L., Lizzio, Marco Maria, Tamburrini, Enrica, Natalello, Gerlando, Gigante, Laura, Bruno, D., Verardi, Lucrezia, Taddei, Eleonora, Calabrese, Anna Chiara, Lombardi, Francesca, Bernabei, Roberto, Cauda, Roberto, Franceschi, Francesco, Landolfi, Raffaele, Richeldi, Luca, Sanguinetti, Maurizio, Fantoni, Massimo, Antonelli, Massimo, Gasbarrini, Antonio, Gremese E. (ORCID:0000-0002-2248-1058), Cingolani A. (ORCID:0000-0002-3793-2755), Bosello S. L. (ORCID:0000-0002-4837-447X), Alivernini S. (ORCID:0000-0002-7383-4212), Tolusso B. (ORCID:0000-0002-9108-6609), Landi F. (ORCID:0000-0002-3472-1389), Pompili M. (ORCID:0000-0001-6699-7980), Murri R. (ORCID:0000-0003-4263-7854), Santoliquido A. (ORCID:0000-0003-1539-4017), Sali M. (ORCID:0000-0003-3609-2990), De Pascale G. (ORCID:0000-0002-8255-0676), Gabrielli M., Biscetti F. (ORCID:0000-0001-7449-657X), Montalto M. (ORCID:0000-0001-8819-3684), Tosoni A., Gambassi G. (ORCID:0000-0002-7030-9359), Rapaccini G. L. (ORCID:0000-0002-6467-857X), Iaconelli A., Lizzio M. M., Tamburrini E. (ORCID:0000-0003-4930-426X), Natalello G., Gigante L., Verardi L., Taddei E., Calabrese A., Lombardi F. (ORCID:0000-0001-5757-8346), Bernabei R. (ORCID:0000-0002-9197-004X), Cauda R. (ORCID:0000-0002-1498-4229), Franceschi F. (ORCID:0000-0001-6266-445X), Landolfi R. (ORCID:0000-0002-7913-8576), Richeldi L. (ORCID:0000-0001-8594-1448), Sanguinetti M. (ORCID:0000-0002-9780-7059), Fantoni M. (ORCID:0000-0001-6913-8460), Antonelli M. (ORCID:0000-0003-3007-1670), and Gasbarrini A. (ORCID:0000-0002-7278-4823)

Abstract

Background: Interleukin-6 signal blockade showed preliminary beneficial effects in treating inflammatory response against SARS-CoV-2 leading to severe respiratory distress. Herein we describe the outcomes of off-label intravenous use of Sarilumab in severe SARS-CoV-2-related pneumonia. Methods: 53 patients with SARS-CoV-2 severe pneumonia received intravenous Sarilumab; pulmonary function improvement or Intensive Care Unit (ICU) admission rate in medical wards, live discharge rate in ICU treated patients and safety profile were recorded. Sarilumab 400 mg was administered intravenously on day 1, with eventual additional infusion based on clinical judgement, and patients were followed for at least 14 days, unless previously discharged or dead. Findings: Of the 53 SARS-CoV-2pos patients receiving Sarilumab, 39(73·6%) were treated in medical wards [66·7% with a single infusion; median PaO2/FiO2:146(IQR:120–212)] while 14(26·4%) in ICU [92·6% with a second infusion; median PaO2/FiO2: 112(IQR:100–141.5)]. Within the medical wards, 7(17·9%) required ICU admission, 4 of whom were re-admitted to the ward within 5–8 days. At 19 days median follow-up, 89·7% of medical inpatients significantly improved (46·1% after 24 h, 61·5% after 3 days), 70·6% were discharged from the hospital and 85·7% no longer needed oxygen therapy. Within patients receiving Sarilumab in ICU, 64·2% were discharged from ICU to the ward and 35·8% were still alive at the last follow-up. Overall mortality rate was 5·7%. Interpretation: IL-6R inhibition appears to be a potential treatment strategy for severe SARS-CoV-2 pneumonia and intravenous Sarilumab seems a promising treatment approach showing, in the short term, an important clinical outcome and good safety.

Published
2020

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