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1. GM-CSF blockade with mavrilimumab in severe COVID-19 pneumonia and systemic hyperinflammation: a single-centre, prospective cohort study

Author: De Luca G., Cavalli G., Campochiaro C., Della-Torre E., Angelillo P., Tomelleri A., Boffini N., Tentori S., Mette F., Farina N., Rovere-Querini P., Ruggeri A., D'Aliberti T., Scarpellini P., Landoni G., De Cobelli F., Paolini J. F., Zangrillo A., Tresoldi M., Trapnell B. C., Ciceri F., Dagna L., DE LUCA , GIACOMO, De Luca, G., Cavalli, G., Campochiaro, C., Della-Torre, E., Angelillo, P., Tomelleri, A., Boffini, N., Tentori, S., Mette, F., Farina, N., Rovere-Querini, P., Ruggeri, A., D'Aliberti, T., Scarpellini, P., Landoni, G., De Cobelli, F., Paolini, J. F., Zangrillo, A., Tresoldi, M., Trapnell, B. C., Ciceri, F., Dagna, L., and DE LUCA, Giacomo
Subjects: Mechanical ventilation, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, medicine.medical_treatment, Immunology, medicine.disease, Article, Blockade, Single centre, Pneumonia, Mavrilimumab, Rheumatology, Internal medicine, medicine, Immunology and Allergy, Prospective cohort study, Adverse effect, business
Abstract: Summary Background Mortality in patients with COVID-19 pneumonia and systemic hyperinflammation is high. We aimed to examine whether mavrilimumab, an anti-granulocyte–macrophage colony-stimulating factor receptor-α monoclonal antibody, added to standard management, improves clinical outcomes in patients with COVID-19 pneumonia and systemic hyperinflammation. Methods This single-centre prospective cohort study included patients aged 18 years or older who were admitted to San Raffaele Hospital (Milan, Italy) with severe COVID-19 pneumonia, hypoxia, and systemic hyperinflammation. Patients received a single intravenous dose (6 mg/kg) of mavrilimumab added to standard care given by the hospital at the time. The control group consisted of contemporaneous patients with similar baseline characteristics who received standard care at the same hospital. The main outcome was time to clinical improvement (defined as improvement of two or more points on the seven-point ordinal scale of clinical status). Other outcomes included proportion of patients achieving clinical improvement, survival, mechanical ventilation-free survival, and time to fever resolution. Adverse events were monitored daily. Findings Between March 17 and April 15, 2020, 13 non-mechanically ventilated patients (median age 57 years [IQR 52–58], 12 [92%] men) received mavrilimumab and 26 patients (median age 60 [IQR 53–67], 17 [65%] men) in the control group received standard care. During the 28-day follow-up, no patients in the mavrilimumab group died, and seven (27%) patients in the control group died (p=0·086). At day 28, all patients in the mavrilimumab group and 17 (65%) patients in the control group showed clinical improvement (p=0·030), with earlier improvement in the mavrilimumab than in the control group (mean time to improvement 8 days [IQR 5 to 11] vs 19 days [11 to >28], p=0·0001). By day 28, one (8%) patient in the mavrilimumab group progressed to mechanical ventilation compared with nine (35%) patients in the control group who progressed to mechanical ventilation or died (p=0·14). By day 14, fever resolved in ten (91%) of 11 febrile patients in the mavrilimumab group, compared with 11 (61%) of 18 febrile patients in the control group (p=0·18); fever resolution was faster in mavrilimumab recipients versus controls (median time to resolution 1 day [IQR 1 to 2] vs 7 days [3 to >14], p=0·0093). Mavrilimumab was well tolerated, with no infusion reactions. Three (12%) patients in the control group developed infectious complications. Interpretation Mavrilimumab treatment was associated with improved clinical outcomes compared with standard care in non-mechanically ventilated patients with severe COVID-19 pneumonia and systemic hyperinflammation. Treatment was well tolerated. Confirmation of efficacy requires controlled testing. Funding IRCCS San Raffaele Scientific Institute.
Published: 2020

2. Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study

Author: Cavalli G, De Luca G, Campochiaro C, Della-Torre E, Ripa M, Canetti D, Oltolini C, Castiglioni B, Tassan Din C, Boffini N, Tomelleri A, Farina N, Ruggeri A, Rovere-Querini P, Di Lucca G, Martinenghi S, Scotti R, Tresoldi M, Ciceri F, Landoni G, Zangrillo A, Scarpellini P, Dagna L, DE LUCA , GIACOMO, Cavalli, G, De Luca, G, Campochiaro, C, Della-Torre, E, Ripa, M, Canetti, D, Oltolini, C, Castiglioni, B, Tassan Din, C, Boffini, N, Tomelleri, A, Farina, N, Ruggeri, A, Rovere-Querini, P, Di Lucca, G, Martinenghi, S, Scotti, R, Tresoldi, M, Ciceri, F, Landoni, G, Zangrillo, A, Scarpellini, P, Dagna, L, and DE LUCA, Giacomo
Subjects: Mechanical ventilation, ARDS, Anakinra, medicine.medical_specialty, education.field_of_study, business.industry, medicine.medical_treatment, Standard treatment, Immunology, Population, Retrospective cohort study, medicine.disease, Article, Rheumatology, Intensive care, Internal medicine, medicine, Immunology and Allergy, Respiratory function, business, education, medicine.drug
Abstract: Summary Background Mortality of patients with coronavirus disease 2019 (COVID-19), acute respiratory distress syndrome (ARDS), and systemic inflammation is high. In areas of pandemic outbreak, the number of patients can exceed maximum capacity of intensive care units (ICUs), and, thus, these individuals often receive non-invasive ventilation outside of the ICU. Effective treatments for this population are needed urgently. Anakinra is a recombinant interleukin-1 receptor antagonist that might be beneficial in this patient population. Methods We conducted a retrospective cohort study at the San Raffaele Hospital in Milan, Italy. We included consecutive patients (aged ≥18 years) with COVID-19, moderate-to-severe ARDS, and hyperinflammation (defined as serum C-reactive protein ≥100 mg/L, ferritin ≥900 ng/mL, or both) who were managed with non-invasive ventilation outside of the ICU and who received standard treatment of 200 mg hydroxychloroquine twice a day orally and 400 mg lopinavir with 100 mg ritonavir twice a day orally. We compared survival, mechanical ventilation-free survival, changes in C-reactive protein, respiratory function, and clinical status in a cohort of patients who received additional treatment with anakinra (either 5 mg/kg twice a day intravenously [high dose] or 100 mg twice a day subcutaneously [low dose]) with a retrospective cohort of patients who did not receive anakinra (referred to as the standard treatment group). All outcomes were assessed at 21 days. This study is part of the COVID-19 Biobank study, which is registered with ClinicalTrials.gov , NCT04318366 . Findings Between March 17 and March 27, 2020, 29 patients received high-dose intravenous anakinra, non-invasive ventilation, and standard treatment. Between March 10 and March 17, 2020, 16 patients received non-invasive ventilation and standard treatment only and comprised the comparison group for this study. A further seven patients received low-dose subcutaneous anakinra in addition to non-invasive ventilation and standard treatment; however, anakinra treatment was interrupted after 7 days because of a paucity of effects on serum C-reactive protein and clinical status. At 21 days, treatment with high-dose anakinra was associated with reductions in serum C-reactive protein and progressive improvements in respiratory function in 21 (72%) of 29 patients; five (17%) patients were on mechanical ventilation and three (10%) died. In the standard treatment group, eight (50%) of 16 patients showed respiratory improvement at 21 days; one (6%) patient was on mechanical ventilation and seven (44%) died. At 21 days, survival was 90% in the high-dose anakinra group and 56% in the standard treatment group (p=0·009). Mechanical ventilation-free survival was 72% in the anakinra group versus 50% in the standard treatment group (p=0·15). Bacteraemia occurred in four (14%) of 29 patients receiving high-dose anakinra and two (13%) of 16 patients receiving standard treatment. Discontinuation of anakinra was not followed by inflammatory relapses. Interpretation In this retrospective cohort study of patients with COVID-19 and ARDS managed with non-invasive ventilation outside of the ICU, treatment with high-dose anakinra was safe and associated with clinical improvement in 72% of patients. Confirmation of efficacy will require controlled trials. Funding None.
Published: 2020

3. Treatment of Dilated Cardiomyopathy With Interleukin-1 Inhibition

Author: De Luca, Giacomo, Campochiaro, Corrado, Dinarello, Charles A, Dagna, Lorenzo, Cavalli, Giulio, DE LUCA , GIACOMO, De Luca, Giacomo, Campochiaro, Corrado, Dinarello, Charles A, Dagna, Lorenzo, Cavalli, Giulio, and DE LUCA, Giacomo
Subjects: 0301 basic medicine, medicine.medical_specialty, Myocarditis, biology, business.industry, Cardiomyopathy, Interleukin, Dilated cardiomyopathy, Inflammation, General Medicine, 030204 cardiovascular system & hematology, medicine.disease, Troponin, Gastroenterology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Fibrosis, Heart failure, Internal medicine, Internal Medicine, biology.protein, Medicine, medicine.symptom, business
Published: 2018

4. Impact of systemic immune-mediated diseases on clinical features and prognosis of patients with biopsy-proved myocarditis

Author: Peretto, Giovanni, Sala, Simone, De Luca, Giacomo, Campochiaro, Corrado, Sartorelli, Silvia, Cappelletti, Alberto M., Rizzo, Stefania, Palmisano, Anna, Esposito, Antonio, Margonato, Alberto, Tresoldi, Moreno, Thiene, Gaetano, Basso, Cristina, Dagna, Lorenzo, Della Bella, Paolo, PALMISANO , ANNA, Peretto, Giovanni, Sala, Simone, De Luca, Giacomo, Campochiaro, Corrado, Sartorelli, Silvia, Cappelletti, Alberto M., Rizzo, Stefania, Palmisano, Anna, Esposito, Antonio, Margonato, Alberto, Tresoldi, Moreno, Thiene, Gaetano, Basso, Cristina, Dagna, Lorenzo, and Della Bella, Paolo
Subjects: Adult, Male, medicine.medical_specialty, Myocarditis, Cardiac magnetic resonance, Biopsy, Systemic immune-mediated disease, Autoimmune, Endomyocardial biopsy, Outcome, Systemic immune-mediated diseases, Myocarditi, Context (language use), 030204 cardiovascular system & hematology, 03 medical and health sciences, Pericarditis, 0302 clinical medicine, Immune system, Fibrosis, Internal medicine, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Aged, medicine.diagnostic_test, business.industry, Myocardium, Middle Aged, medicine.disease, Prognosis, Immune System Diseases, Female, Presentation (obstetrics), business, Cardiology and Cardiovascular Medicine, Follow-Up Studies
Abstract: Introduction: Myocarditis has been described in association with many systemic immune-mediated diseases (SIDs). However, the role of SIDs in influencing clinical presentation and outcome of patients with a new diagnosis of biopsy-proved myocarditis, has never been investigated so far. Methods: We enrolled 25 consecutive cases with biopsy-proved myocarditis in the context of SIDs, and controls with isolated myocarditis, matched 1:1 by age, gender, ethnicity and clinical presentation. All of the patients presented with acute symptoms, normal coronary arteries, and no previous history of myocarditis. Detailed diagnostic workup, including blood exams, echocardiogram, arrhythmia monitoring and cardiac magnetic resonance (CMR) were obtained at baseline and at defined time points, up to 12-month follow-up (FU). Results: At presentation, patients with SIDs had more commonly inflammatory biomarkers elevation, signs of associated pericarditis, and replacement fibrosis at histology, as compared to controls (18 vs. 6, 20 vs. 12, and 21 vs. 11, respectively; all p < 0.05). The Lake Louise criteria at CMR were negative in 19 vs. 10 patients with and without underlying SIDs, respectively (p = 0.021). Baseline ECG, in-hospital arrhythmia telemonitoring and echocardiographic findings were not significantly different between groups (all p = n.s.). At 12-month FU, the composite major endpoint of cardiac death, end-stage heart failure or malignant ventricular arrhythmias was significantly more common in cases than in controls (7 vs. 1, respectively, p = 0.049). Conclusion: In patients with a new diagnosis of myocarditis, the presence of underlying SIDs is associated with distinct baseline clinical features and a significantly worse 1-year outcome.
Published: 2019

5. Arrhythmias in myocarditis: State of the art

Author: Peretto, Giovanni, Sala, Simone, Rizzo, Stefania, De Luca, Giacomo, Campochiaro, Corrado, Sartorelli, Silvia, Bendetti, Giulia, Palmisano, Anna, Esposito, Antonio, Tresoldi, Moreno, Thiene, Gaetano, Basso, Cristina, Della Bella, Paolo, PALMISANO , ANNA, Peretto, Giovanni, Sala, Simone, Rizzo, Stefania, De Luca, Giacomo, Campochiaro, Corrado, Sartorelli, Silvia, Bendetti, Giulia, Palmisano, Anna, Esposito, Antonio, Tresoldi, Moreno, Thiene, Gaetano, Basso, Cristina, and Della Bella, Paolo
Subjects: medicine.medical_specialty, Myocarditis, Myocarditi, Disease, 030204 cardiovascular system & hematology, Ventricular tachycardia, Imaging, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), Epidemiology, medicine, Humans, In patient, 030212 general & internal medicine, Intensive care medicine, Inflammation, business.industry, Myocardial inflammation, Disease Management, Arrhythmias, Cardiac, Limiting, medicine.disease, Prognosis, Arrhythmia, Endomyocardial biopsy, Etiology, Cardiology and Cardiovascular Medicine, business
Abstract: Many kinds of arrhythmias may occur in patients with myocarditis at any stage of the disease. However, as compared to the other clinical presentations, arrhythmic myocarditis has been poorly described so far in the literature. In fact, arrhythmias occurring in either ongoing or previous myocardial inflammation are complex and heterogeneous, and the disease itself is often underdiagnosed, thus limiting data collection and interpretation. However, differently from the other clinical presenations, arrhythmic myocarditis require specific diagnostic, prognostic and therapeutic considerations. The aim of the current paper is to critically summarize the state of the art on myocarditis presenting with arrhythmias in terms of epidemiology, aetiology, diagnosis, prognosis and treatment.
Published: 2019

6. Pattern of comorbidities and 1-year mortality in elderly patients with COPD hospitalized in internal medicine wards: data from the RePoSI Registry

Author: Argano, Christiano, Scichilone, Nicola, Natoli, Giuseppe, Nobili, Alessandro, Corazza, Gino Roberto, Mannucci, Pier Mannuccio, Perticone, Francesco, Corrao, Salvatore, Pietrangelo, Antonello, Licata, Giuseppe, Violi, Francesco, Marengoni, Alessandra, Salerno, Francesco, Cesari, Matteo, Tettamanti, Mauro, Pasina, Luca, Franchi, Carlotta, Miglio, Gabriella, Cortesi, Laura, Ardoino, Ilaria, Novella, Alessio, Prisco, Domenico, Silvestri, Elena, Emmi, Giacomo, Bettiol, Alessandra, Caterina, Cenci, Biolo, Gianni, Zanetti, Michela, Guadagni, Martina, Zaccari, Michele, Chiuch, Massimiliano, Vanoli, Massimo, Grignani, Giulia, Pulixi, Edoardo Alessandro, Bernardi, Mauro, Bassi, Silvia Li, Santi, Luca, Zaccherini, Giacomo, Lupattelli, Graziana, Mannarino, Elmo, Bianconi, Vanessa, Paciullo, Francesco, Alcidi, Riccardo, Nuti, Ranuccio, Valenti, Roberto, Ruvio, Martina, Cappelli, Silvia, Palazzuoli, Alberto, Girelli, Domenico, Busti, Fabiana, Marchi, Giacomo, Barbagallo, Mario, Dominguez, Ligia, Cocita, Floriana, Beneduce, Vincenza, Plances, Lidia, Mularo, Salvatore, Raspanti, Massimo, Cavallaro, Federica, Zoli, Marco, Lazzari, Ilaria, Brunori, Mattia, Fabbri, Elisa, Magalotti, Donatella, Arnò, Raffaella, Pasini, Franco Laghi, Capecchi, Pier Leopoldo, Palasciano, Giuseppe, Modeo, Maria Ester, Di Gennaro, Carla, Cappellini, Maria Domenica, Maira, Diletta, Di Stefano, Valeria, Fabio, Giovanna, Seghezzi, Sonia, Mancarella, Marta, De Amicis, Margherita Migone, De Luca, Giacomo, Scaramellini, Natalia, Rossi, Paolo Dionigi, Damanti, Sarah, Clerici, Marta, Conti, Federica, Bonini, Giulia, Ottolini, Barbara Brignolo, Di Sabatino, Antonio, Miceli, Emanuela, Lenti, Marco Vincenzo, Pisati, Martina, Dominioni, Costanza Caccia, Murialdo, Giovanni, Marra, Alessio, Cattaneo, Federico, Pontremoli, Roberto, Beccati, Valentina, Nobili, Giulia, Secchi, Maria Beatrice, Ghelfi, Davide, Anastasio, Luigi, Sofia, Lucia, Carbone, Maria, Cipollone, Francesco, Guagnano, Maria Teresa, Valeriani, Emanuele, Rossi, Ilaria, Mancuso, Gerardo, Calipari, Daniela, Bartone, Mosè, Delitala, Giuseppe, Berria, Maria, Pes, Chiara, Delitala, Alessandro, Muscaritoli, Maurizio, Molfino, Alessio, Petrillo, Enrico, Zuccalà, Giuseppe, D’Aurizio, Gabriella, Romanelli, Giuseppe, Zucchelli, Alberto, Manzoni, Francesca, Volpini, Andrea, Picardi, Antonio, Gentilucci, Umberto Vespasiani, Gallo, Paolo, Dell’Unto, Chiara, Annoni, Giorgio, Corsi, Maurizio, Bellelli, Giuseppe, Zazzetta, Sara, Mazzola, Paolo, Szabo, Hajnalka, Bonfanti, Alessandra, Arturi, Franco, Succurro, Elena, Rubino, Mariangela, Tassone, Bruno, Sesti, Giorgio, Serra, Maria Grazia, Bleve, Maria Antonietta, Gasbarrone, Laura, Sajeva, Maria Rosaria, Brucato, Antonio, Ghidoni, Silvia, Fabris, Fabrizio, Bertozzi, Irene, Bogoni, Giulia, Rabuini, Maria Victoria, Cosi, Elisabetta, Scarinzi, Paolo, Amabile, Annalisa, Omenetto, Elisabetta, Prandini, Tancredi, Manfredini, Roberto, Fabbian, Fabio, Boari, Benedetta, De Giorgi, Alfredo, Tiseo, Ruana, De Giorgio, Roberto, Paolisso, Giuseppe, Rizzo, Maria Rosaria, Borghi, Claudio, Strocchi, Enrico, Ianniello, Eugenia, Soldati, Mario, Sabbà, Carlo, Vella, Francesco Saverio, Suppressa, Patrizia, Schilardi, Andrea, Loparco, Francesca, De Vincenzo, Giovanni Michele, Comitangelo, Alessio, Amoruso, Emanuele, Fenoglio, Luigi, Falcetta, Andrea, Bracco, Christian, Fracanzani Silvia Fargion, Anna L., Tiraboschi, Silvia, Cespiati, Annalisa, Oberti, Giovanna, Sigon, Giordano, Peyvandi, Flora, Rossio, Raffaella, Ferrari, Barbara, Colombo, Giulia, Agosti, Pasquale, Monzani, Valter, Savojardo, Valeria, Folli, Christian, Ceriani, Giuliana, Pallini, Giada, Dallegri, Franco, Ottonello, Luciano, Liberale, Luca, Caserza, Lara, Salam, Kassem, Liberato, Nicola Lucio, Tognin, Tiziana, Bianchi, Giovanni Battista, Giaquinto, Sabrina, Purrello, Francesco, Di Pino, Antonino, Piro, Salvatore, Rozzini, Renzo, Falanga, Lina, Spazzini, Elena, Ferrandina, Camillo, Montrucchio, Giuseppe, Petitti, Paolo, Peasso, Paolo, Favale, Edoardo, Poletto, Cesare, Salmi, Raffaella, Gaudenzi, Piergiorgio, Perri, Ludovica, Landolfi, Raffaele, Montalto, Massimo, Mirijello, Antonio, Guasti, Luigina, Castiglioni, Luana, Maresca, Andrea, Squizzato, Alessandro, Campiotti, Leonardo, Grossi, Alessandra, Bertolotti, Marco, Mussi, Chiara, Lancellotti, Giulia, Libbra, Maria Vittoria, Dondi, Giulia, Pellegrini, Elisa, Carulli, Lucia, Galassi, Matteo, Grassi, Yasmine, Perticone, Maria, Battaglia, Rosa, FIlice, Marco, Maio, Raffaele, Stanghellini, Vincenzo, Ruggeri, Eugenio, del Vecchio, Sara, Salvi, Andrea, Leonardi, Roberto, Damiani, Giampaolo, Capeci, William, Gabrielli, Armando, Mattioli, Massimo, Martino, Giuseppe Pio, Biondi, Lorenzo, Pettinari, Pietro, Ghio, Riccardo, Col, Anna Dal, Minisola, Salvatore, Colangelo, Luciano, Cilli, Mirella, Labbadia, Giancarlo, Afeltra, Antonella, Marigliano, Benedetta, Pipita, Maria Elena, Castellino, Pietro, Zanoli, Luca, Pignataro, Samuele, Gennaro, Alfio, Blanco, Julien, Saracco, Valter, Fogliati, Marisa, Bussolino, Carlo, Mete, Francesca, Gino, Miriam, Cittadini, Antonio, Vigorito, Carlo, Arcopinto, Michele, Salzano, Andrea, Bobbio, Emanuele, Marra, Alberto Maria, Sirico, Domenico, Moreo, Guido, Gasparini, Francesca, Prolo, Silvia, Pina, Gloria, Ballestrero, Alberto, Ferrando, Fabio, Berra, Sergio, Dassi, Simonetta, Nava, Maria Cristina, Graziella, Bruno, Baldassarre, Stefano, Fragapani, Salvatore, Gruden, Gabriella, Galanti, Giorgio, Mascherini, Gabriele, Petri, Cristian, Stefani, Laura, Girino, Margherita, Piccinelli, Valeria, Nasso, Francesco, Gioffrè, Vincenza, Pasquale, Maria, Scattolin, Giuseppe, Martinelli, Sergio, Turrin, Mauro, Sechi, Leonardo, Catena, Cristina, Colussi, Gianluca, Passariello, Nicola, Rinaldi, Luca, Berti, Franco, Famularo, Giuseppe, Tarsitani, Patrizia, Castello, Roberto, Pasino, Michela, Ceda, Gian Paolo, Maggio, Marcello Giuseppe, Morganti, Simonetta, Artoni, Andrea, Del Giacco, Stefano, Firinu, Davide, Losa, Francesca, Paoletti, Giovanni, Costanzo, Giulia, Montalto, Giuseppe, Licata, Anna, Malerba, Valentina, Montalto, Filippo Alessandro, Lasco, Antonino, Basile, Giorgio, Catalano, Antonino, Malatino, Lorenzo, Stancanelli, Benedetta, Terranova, Valentina, Di Marca, Salvatore, Di Quattro, Rosario, La Malfa, Lara, Caruso, Rossella, Mecocci, Patrizia, Ruggiero, Carmelinda, Boccardi, Virginia, Meschi, Tiziana, Lauretani, Fulvio, Ticinesi, Andrea, Nouvenne, Antonio, Minuz, Pietro, Fondrieschi, Luigi, Pirisi, Mario, Fra, Gian Paolo, Sola, Daniele, Porta, Massimo, Riva, Piero, Quadri, Roberto, Larovere, Erica, Novelli, Marco, Scanzi, Giorgio, Mengoli, Caterina, Provini, Stella, Ricevuti, Laura, Simeone, Emilio, Scurti, Rosa, Tolloso, Fabio, Tarquini, Roberto, Valoriani, Alice, Dolenti, Silvia, Vannini, Giulia, Tedeschi, Alberto, Trotta, Lucia, Volpi, Riccardo, Bocchi, Pietro, Vignali, Alessandro, Harari, Sergio, Lonati, Chiara, Cattaneo, Mara, Napoli, Federico, Argano, Christiano, Scichilone, Nicola, Natoli, Giuseppe, Nobili, Alessandro, Corazza, Gino Roberto, Mannucci, Pier Mannuccio, Perticone, Francesco, Corrao, Salvatore, Paolisso, Giuseppe, Rizzo, Maria Rosaria, Argano, C., Scichilone, N., Natoli, G., Nobili, A., Corazza, G. R., Mannucci, P. M., Perticone, F., Corrao, S., Pietrangelo, A., Licata, G., Violi, F., Marengoni, A., Salerno, F., Cesari, M., Tettamanti, M., Pasina, L., Franchi, C., Miglio, G., Cortesi, L., Ardoino, I., Novella, A., Prisco, D., Silvestri, E., Emmi, G., Bettiol, A., Caterina, C., Biolo, G., Zanetti, M., Guadagni, M., Zaccari, M., Chiuch, M., Vanoli, M., Grignani, G., Pulixi, E. A., Bernardi, M., Bassi, S. L., Santi, L., Zaccherini, G., Lupattelli, G., Mannarino, E., Bianconi, V., Paciullo, F., Alcidi, R., Nuti, R., Valenti, R., Ruvio, M., Cappelli, S., Palazzuoli, A., Girelli, D., Busti, F., Marchi, G., Barbagallo, M., Dominguez, L., Cocita, F., Beneduce, V., Plances, L., Mularo, S., Raspanti, M., Cavallaro, F., Zoli, M., Lazzari, I., Brunori, M., Fabbri, E., Magalotti, D., Arno, R., Pasini, F. L., Capecchi, P. L., Palasciano, G., Modeo, M. E., Di Gennaro, C., Cappellini, M. D., Maira, D., Di Stefano, V., Fabio, G., Seghezzi, S., Mancarella, M., De Amicis, M. M., De Luca, G., Scaramellini, N., Rossi, P. D., Damanti, S., Clerici, M., Conti, F., Bonini, G., Ottolini, B. B., Di Sabatino, A., Miceli, E., Lenti, M. V., Pisati, M., Dominioni, C. C., Murialdo, G., Marra, A., Cattaneo, F., Pontremoli, R., Beccati, V., Nobili, G., Secchi, M. B., Ghelfi, D., Anastasio, L., Sofia, L., Carbone, M., Cipollone, F., Guagnano, M. T., Valeriani, E., Rossi, I., Mancuso, G., Calipari, D., Bartone, M., Delitala, G., Berria, M., Pes, C., Delitala, A., Muscaritoli, M., Molfino, A., Petrillo, E., Zuccala, G., D'Aurizio, G., Romanelli, G., Zucchelli, A., Manzoni, F., Volpini, A., Picardi, A., Gentilucci, U. V., Gallo, P., Dell'Unto, C., Annoni, G., Corsi, M., Bellelli, G., Zazzetta, S., Mazzola, P., Szabo, H., Bonfanti, A., Arturi, F., Succurro, E., Rubino, M., Tassone, B., Sesti, G., Serra, M. G., Bleve, M. A., Gasbarrone, L., Sajeva, M. R., Brucato, A., Ghidoni, S., Fabris, F., Bertozzi, I., Bogoni, G., Rabuini, M. V., Cosi, E., Scarinzi, P., Amabile, A., Omenetto, E., Prandini, T., Manfredini, R., Fabbian, F., Boari, B., De Giorgi, A., Tiseo, R., De Giorgio, R., Paolisso, G., Rizzo, M. R., Borghi, C., Strocchi, E., Ianniello, E., Soldati, M., Sabba, C., Vella, F. S., Suppressa, P., Schilardi, A., Loparco, F., De Vincenzo, G. M., Comitangelo, A., Amoruso, E., Fenoglio, L., Falcetta, A., Bracco, C., Fracanzani Silvia Fargion, A. L., Tiraboschi, S., Cespiati, A., Oberti, G., Sigon, G., Peyvandi, F., Rossio, R., Ferrari, B., Colombo, G., Agosti, P., Monzani, V., Savojardo, V., Folli, C., Ceriani, G., Pallini, G., Dallegri, F., Ottonello, L., Liberale, L., Caserza, L., Salam, K., Liberato, N. L., Tognin, T., Bianchi, G. B., Giaquinto, S., Purrello, F., Di Pino, A., Piro, S., Rozzini, R., Falanga, L., Spazzini, E., Ferrandina, C., Montrucchio, G., Petitti, P., Peasso, P., Favale, E., Poletto, C., Salmi, R., Gaudenzi, P., Perri, L., Landolfi, R., Montalto, M., Mirijello, A., Guasti, L., Castiglioni, L., Maresca, A., Squizzato, A., Campiotti, L., Grossi, A., Bertolotti, M., Mussi, C., Lancellotti, G., Libbra, M. V., Dondi, G., Pellegrini, E., Carulli, L., Galassi, M., Grassi, Y., Perticone, M., Battaglia, R., Filice, M., Maio, R., Stanghellini, V., Ruggeri, E., del Vecchio, S., Salvi, A., Leonardi, R., Damiani, G., Capeci, W., Gabrielli, A., Mattioli, M., Martino, G. P., Biondi, L., Pettinari, P., Ghio, R., Col, A. D., Minisola, S., Colangelo, L., Cilli, M., Labbadia, G., Afeltra, A., Marigliano, B., Pipita, M. 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Malfa L., Caruso R., Mecocci P., Ruggiero C., Boccardi V., Meschi T., Lauretani F., Ticinesi A., Nouvenne A., Minuz P., Fondrieschi L., Pirisi M., Fra G.P., Sola D., Porta M., Riva P., Quadri R., Larovere E., Novelli M., Scanzi G., Mengoli C., Provini S., Ricevuti L., Simeone E., Scurti R., Tolloso F., Tarquini R., Valoriani A., Dolenti S., Vannini G., Tedeschi A., Trotta L., Volpi R., Bocchi P., Vignali A., Harari S., Lonati C., Cattaneo M., and Napoli F.
Subjects: Male, medicine.medical_specialty, Chronic Obstructive, Cirrhosis, Socio-culturale, Comorbidity, 030204 cardiovascular system & hematology, comorbidities, elderly, Pulmonary Disease, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Internal medicine, medicine, 80 and over, COPD, Humans, 030212 general & internal medicine, LS4_4, Registries, Hospital Mortality, COPD, comorbidities, elderly, internal medicine, in-hospital mortality, Depression (differential diagnoses), Cause of death, Aged, Retrospective Studies, 1-year mortality, 3-month mortality, internal medicine, in-hospital mortality, Aged, 80 and over, business.industry, medicine.disease, Im - Original, Female, Internal Medicine, Clinical diagnosis, Cohort, Emergency Medicine, 1-year mortality, 3-month mortality, COPD, comorbidities, elderly, internal medicine, in-hospital mortality, Observational study, business, 1 year mortality
Abstract: Currently, chronic obstructive pulmonary disease (COPD) represents the fourth cause of death worldwide with significant economic burden. Comorbidities increase in number and severity with age and are identified as important determinants that influence the prognosis. In this observational study, we retrospectively analyzed data collected from the RePoSI register. We aimed to investigate comorbidities and outcomes in a cohort of hospitalized elderly patients with the clinical diagnosis of COPD. Socio-demographic, clinical characteristics and laboratory findings were considered. The association between variables and in-hospital, 3-month and 1-year follow-up were analyzed. Among 4696 in-patients, 932 (19.8%) had a diagnosis of COPD. Patients with COPD had more hospitalization, a significant overt cognitive impairment, a clinically significant disability and more depression in comparison with non-COPD subjects. COPD patients took more drugs, both at admission, in-hospital stay, discharge and 3-month and 1-year follow-up. 14 comorbidities were more frequent in COPD patients. Cerebrovascular disease was an independent predictor of in-hospital mortality. At 3-month follow-up, male sex and hepatic cirrhosis were independently associated with mortality. ICS-LABA therapy was predictor of mortality at in-hospital, 3-month and 1-year follow-up. This analysis showed the severity of impact of COPD and its comorbidities in the real life of internal medicine and geriatric wards. Electronic supplementary material The online version of this article (10.1007/s11739-020-02412-1) contains supplementary material, which is available to authorized users.
Published: 2020

7. Prognostic relevance of glomerular filtration rate estimation obtained through different equations in hospitalized elderly patients

Author: Gallo, Paolo, De Vincentis, Antonio, Pedone, Claudio, Nobili, Alessandro, Tettamanti, Mauro, Gentilucci, Umberto Vespasiani, Picardi, Antonio, Mannucci, Pier Mannuccio, Incalzi, Raffaele Antonelli, Prisco, Domenico, Silvestri, Elena, Emmi, Giacomo, Bettiol, Alessandra, Caterina, Cenci, Biolo, Gianni, Zanetti, Michela, Guadagni, Martina, Zaccari, Michele, Chiuch, Massimiliano, Vanoli, Massimo, Grignani, Giulia, Pulixi, Edoardo Alessandro, Bernardi, Mauro, Bassi, Silvia Li, Santi, Luca, Zaccherini, Giacomo, Lupattelli, Graziana, Mannarino, Elmo, Bianconi, Vanessa, Paciullo, Francesco, Alcidi, Riccardo, Nuti, Ranuccio, Valenti, Roberto, Ruvio, Martina, Cappelli, Silvia, Palazzuoli, Alberto, Girelli, Domenico, Busti, Fabiana, Marchi, Giacomo, Barbagallo, Mario, Dominguez, Ligia, Cocita, Floriana, Beneduce, Vincenza, Plances, Lidia, Corrao, Salvatore, Natoli, Giuseppe, Mularo, Salvatore, Raspanti, Massimo, Cavallaro, Federica, Zoli, Marco, Lazzari, Ilaria, Brunori, Mattia, Fabbri, Elisa, Magalotti, Donatella, Arno, Raffaella, Pasini, Franco Laghi, Capecchi, Pier Leopoldo, Palasciano, Giuseppe, Modeo, Maria Ester, Di Gennaro, Carla, Cappellini, Maria Domenica, Maira, Diletta, Di Stefano, Valeria, Fabio, Giovanna, Seghezzi, Sonia, Mancarella, Marta, De Amicis, Margherita Migone, De Luca, Giacomo, Scaramellini, Natalia, Cesari, Matteo, Rossi, Paolo Dionigi, Damanti, Sarah, Clerici, Marta, Conti, Federica, Bonini, Giulia, Ottolini, Barbara Brignolo, Di Sabatino, Antonio, Miceli, Emanuela, Lenti, Marco Vincenzo, Pisati, Martina, Dominioni, Costanza Caccia, Murialdo, Giovanni, Marra, Alessio, Cattaneo, Federico, Pontremoli, Roberto, Beccati, Valentina, Nobili, Giulia, Secchi, Maria Beatrice, Ghelfi, Davide, Anastasio, Luigi, Sofia, Lucia, Carbone, Maria, Cipollone, Francesco, Guagnano, Maria Teresa, Valeriani, Emanuele, Rossi, Ilaria, Mancuso, Gerardo, Calipari, Daniela, Bartone, Mose, Delitala, Giuseppe, Berria, Maria, Pes, Chiara, Delitala, Alessandro, Muscaritoli, Maurizio, Molfino, Alessio, Petrillo, Enrico, Zuccala, Giuseppe, D'Aurizio, Gabriella, Romanelli, Giuseppe, Marengoni, Alessandra, Zucchelli, Alberto, Manzoni, Francesca, Volpini, Andrea, Dell'Unto, Chiara, Annoni, Giorgio, Corsi, Maurizio, Bellelli, Giuseppe, Zazzetta, Sara, Mazzola, Paolo, Szabo, Hajnalka, Bonfanti, Alessandra, Arturi, Franco, Succurro, Elena, Rubino, Mariangela, Tassone, Bruno, Sesti, Giorgio, Serra, Maria Grazia, Bleve, Maria Antonietta, Gasbarrone, Laura, Sajeva, Maria Rosaria, Brucato, Antonio, Ghidoni, Silvia, Fabris, Fabrizio, Bertozzi, Irene, Bogoni, Giulia, Rabuini, Maria Victoria, Cosi, Elisabetta, Scarinzi, Paolo, Amabile, Annalisa, Omenetto, Elisabetta, Prandini, Tancredi, Manfredini, Roberto, Fabbian, Fabio, Boari, Benedetta, De Giorgi, Alfredo, Tiseo, Ruana, De Giorgio, Roberto, Paolisso, Giuseppe, Rizzo, Maria Rosaria, Borghi, Claudio, Strocchi, Enrico, Ianniello, Eugenia, Soldati, Mario, Sabba, Carlo, Vella, Francesco Saverio, Suppressa, Patrizia, Agosti, Pasquale, Schilardi, Andrea, Loparco, Francesca, De Vincenzo, Giovanni Michele, Comitangelo, Alessio, Amoruso, Emanuele, Fenoglio, Luigi, Falcetta, Andrea, Bracco, Christian, Fracanzani, Anna L., Fargion, Silvia, Tiraboschi, Silvia, Cespiati, Annalisa, Oberti, Giovanna, Sigon, Giordano, Peyvandi, Flora, Rossio, Raffaella, Ferrari, Barbara, Colombo, Giulia, Monzani, Valter, Savojardo, Valeria, Folli, Christian, Ceriani, Giuliana, Salerno, Francesco, Pallini, Giada, Dallegri, Franco, Ottonello, Luciano, Liberale, Luca, Caserza, Lara, Salam, Kassem, Liberato, Nicola Lucio, Tognin, Tiziana, Bianchi, Giovanni Battista, Giaquinto, Sabrina, Purrello, Francesco, Di Pino, Antonino, Piro, Salvatore, Rozzini, Renzo, Falanga, Lina, Spazzini, Elena, Ferrandina, Camillo, Montrucchio, Giuseppe, Petitti, Paolo, Peasso, Paolo, Favale, Edoardo, Poletto, Cesare, Salmi, Raffaella, Gaudenzi, Piergiorgio, Violi, Francesco, Perri, Ludovica, Landolfi, Raffaele, Montalto, Massimo, Mirijello, Antonio, Guasti, Luigina, Castiglioni, Luana, Maresca, Andrea, Squizzato, Alessandro, Campiotti, Leonardo, Grossi, Alessandra, Bertolotti, Marco, Mussi, Chiara, Lancellotti, Giulia, Libbra, Maria Vittoria, Dondi, Giulia, Pellegrini, Elisa, Carulli, Lucia, Galassi, Matteo, Grassi, Yasmine, Perticone, Francesco, Perticone, Maria, Battaglia, Rosa, Filice, Marco, Maio, Raffaele, Stanghellini, Vincenzo, Ruggeri, Eugenio, del Vecchio, Sara, Salvi, Andrea, Leonardi, Roberto, Damiani, Giampaolo, Capeci, William, Gabrielli, Armando, Mattioli, Massimo, Martino, Giuseppe Pio, Biondi, Lorenzo, Pettinari, Pietro, Ghio, Riccardo, Dal Col, Anna, Minisola, Salvatore, Colangelo, Luciano, Cilli, Mirella, Labbadia, Giancarlo, Afeltra, Antonella, Marigliano, Benedetta, Pipita, Maria Elena, Castellino, Pietro, Zanoli, Luca, Pignataro, Samuele, Gennaro, Alfio, Blanco, Julien, Saracco, Valter, Fogliati, Marisa, Bussolino, Carlo, Mete, Francesca, Gino, Miriam, Cittadini, Antonio, Vigorito, Carlo, Arcopinto, Michele, Salzano, Andrea, Bobbio, Emanuele, Marra, Alberto Maria, Sirico, Domenico, Moreo, Guido, Gasparini, Francesca, Prolo, Silvia, Pina, Gloria, Ballestrero, Alberto, Ferrando, Fabio, Berra, Sergio, Dassi, Simonetta, Nava, Maria Cristina, Graziella, Bruno, Baldassarre, Stefano, Fragapani, Salvatore, Gruden, Gabriella, Galanti, Giorgio, Mascherini, Gabriele, Petri, Cristian, Stefani, Laura, Girino, Margherita, Piccinelli, Valeria, Nasso, Francesco, Gioffre, Vincenza, Pasquale, Maria, Scattolin, Giuseppe, Martinelli, Sergio, Turrin, Mauro, Sechi, Leonardo, Catena, Cristina, Colussi, Gianluca, Passariello, Nicola, Rinaldi, Luca, Berti, Franco, Famularo, Giuseppe, Tarsitani, Patrizia, Castello, Roberto, Pasino, Michela, Ceda, Gian Paolo, Maggio, Marcello Giuseppe, Morganti, Simonetta, Artoni, Andrea, Del Giacco, Stefano, Firinu, Davide, Losa, Francesca, Paoletti, Giovanni, Costanzo, Giulia, Montalto, Giuseppe, Licata, Anna, Malerba, Valentina, Montalto, Filippo Alessandro, Lasco, Antonino, Basile, Giorgio, Catalano, Antonino, Malatino, Lorenzo, Stancanelli, Benedetta, Terranova, Valentina, Di Marca, Salvatore, Di Quattro, Rosario, La Malfa, Lara, Caruso, Rossella, Mecocci, Patrizia, Ruggiero, Carmelinda, Boccardi, Virginia, Meschi, Tiziana, Lauretani, Fulvio, Ticinesi, Andrea, Nouvenne, Antonio, Minuz, Pietro, Fondrieschi, Luigi, Pirisi, Mario, Fra, Gian Paolo, Sola, Daniele, Porta, Massimo, Riva, Piero, Quadri, Roberto, Larovere, Erica, Novelli, Marco, Scanzi, Giorgio, Mengoli, Caterina, Provini, Stella, Ricevuti, Laura, Simeone, Emilio, Scurti, Rosa, Tolloso, Fabio, Tarquini, Roberto, Valoriani, Alice, Dolenti, Silvia, Vannini, Giulia, Tedeschi, Alberto, Trotta, Lucia, Volpi, Riccardo, Bocchi, Pietro, Vignali, Alessandro, Harari, Sergio, Lonati, Chiara, Cattaneo, Mara, Duque Nieves, Ramirez, Molinero Alberto, Muela, Requejo Pedro, Abad, Pelaez Vanessa, Lopez, Lara, Tamargo, Viros Xavier, Corbella, Francesc, Formiga, Manglano Jesus, Diez, Tello Esperanza, Bejarano, Behamonte Esther, Del Corral, Puras Maria, Sevil, Romero, Manuel, Llorente Blanca, Pinilla, Gonzalez-Cobos Cristina, Lopez, Victoria, Villalba Garcia M., Saez, Lopez, Bosco, Juan, Baena Susana, Sanz, Gallego Marta, Arroyo, Becerra Concepcion, Gonzalez, Moyano Antonio, Fernandez, Gomez Hernandez, Mercedes, Poyato Borrego, Manuel, Cuadros Raquel, Pacheco, Rojas Florencia, Perez, Olid Beatriz, Garcia, Garcia Sara, Carrascosa, Cervellera Alfonso, Gonzalez-Cruz, Martinez Marta, Peinado, Cantero Alberto, Ruiz, Arraigosa Antonio, Albarracin, Guerrero Montserrat, Godoy, Miguel Angel, Baron Ramos, Jose Manuel, Machin, Veleiro Ignacio, Novo, Suarez Lucia, Alvela, Alfonso, Lopez, Bran David, Rubal, Vazquez Iria, Iniguez, and Prego Monica, Rios
Subjects: Male, medicine.medical_specialty, Population, Socio-culturale, Renal function, Disease, 030204 cardiovascular system & hematology, Elderly in-patients, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Acute care, Epidemiology, eGFR, 80 and over, Internal Medicine, medicine, Humans, Renal Insufficiency, Hospital Mortality, 030212 general & internal medicine, Renal Insufficiency, Chronic, Chronic, education, Glomerular filtration rate estimation, Aged, Aged, 80 and over, Estimation, Creatinine, education.field_of_study, business.industry, Prognosis, Female, Italy, Glomerular Filtration Rate, Hospitalization, medicine.disease, Elderly in-patients, Glomerular filtration rate estimation, Prognosis, eGFR, chemistry, business, Kidney disease
Abstract: The estimated glomerular filtration rate (eGFR) is a predictor of important outcomes and its reduction has been associated with the risk of all-cause mortality in both general population and elderly patients. However while reduced renal function is common in older people, the best method for estimating GFR remains unclear, especially in an acute care setting. Most studies analyzing the accuracy of eGFR in the elderly were carried out in different heterogeneous settings. In this study, we compare the prognostic value of different formulas estimating GFR in predicting the risk of in-hospital morbidity and mortality within 3 months from discharge in elderly hospitalized patients. Data were extracted from “Registro Politerapia Societa Italiana di Medicina Interna (REPOSI)”. Patients with available creatinine values at hospital admission were selected and eGFR was calculated according to the different formulas: Cockcroft-Gault, Modification of Diet in Renal Disease equation, Chronic Kidney Disease Epidemiology Collaboration, Berlin Initiative Study and Full Age Spectrum. 4621 patients were included in the analysis. Among these, 4.2% and 14.2% died during hospitalization and within 3 months from discharge, respectively. eGFR > 60 ml/min/1.73 m2 at admission was associated with a very low risk of mortality during the hospital stay and within 90 days from discharge, while an eGFR
Published: 2018

8. Sex-Differences in the Pattern of Comorbidities, Functional Independence, and Mortality in Elderly Inpatients: Evidence from the RePoSI Register

Author: Corrao, Salvatore, Argano, Christiano, Natoli, Giuseppe, Nobili, Alessandro, Corazza, Gino Roberto, Mannucci, Pier Mannuccio, Perticone, Francesco, Prisco, Domenico, Silvestri, Elena, Emmi, Giacomo, Bettiol, Alessandra, Caterina, Cenci, Biolo, Gianni, Zanetti, Michela, Guadagni, Martina, Zaccari, Michele, Chiuch, Massimiliano, Vanoli, Massimo, Grignani, Giulia, Pulixi, Edoardo Alessandro, Bernardi, Mauro, Bassi, Silvia Li, Santi, Luca, Zaccherini, Giacomo, Lupattelli, Graziana, Mannarino, Elmo, Bianconi, Vanessa, Paciullo, Francesco, Alcidi, Riccardo, Nuti, Ranuccio, Valenti, Roberto, Ruvio, Martina, Cappelli, Silvia, Palazzuoli, Alberto, Girelli, Domenico, Busti, Fabiana, Marchi, Giacomo, Barbagallo, Mario, Dominguez, Ligia, Cocita, Floriana, Beneduce, Vincenza, Plances, Lidia, Mularo, Salvatore, Raspanti, Massimo, Cavallaro, Federica, Zoli, Marco, Lazzari, Ilaria, Brunori, Mattia, Fabbri, Elisa, Magalotti, Donatella, Arno, Raffaella, Pasini, Franco Laghi, Capecchi, Pier Leopoldo, Palasciano, Giuseppe, Modeo, Maria Ester, Di Gennaro, Carla, Cappellini, Maria Domenica, Maira, Diletta, Di Stefano, Valeria, Fabio, Giovanna, Seghezzi, Sonia, Mancarella, Marta, De Amicis, Margherita Migone, De Luca, Giacomo, Scaramellini, Natalia, Cesari, Matteo, Rossi, Paolo Dionigi, Damanti, Sarah, Clerici, Marta, Conti, Federica, Bonini, Giulia, Ottolini, Barbara Brignolo, Di Sabatino, Antonio, Miceli, Emanuela, Lenti, Marco Vincenzo, Pisati, Martina, Dominioni, Costanza Caccia, Murialdo, Giovanni, Marra, Alessio, Cattaneo, Federico, Pontremoli, Roberto, Beccati, Valentina, Nobili, Giulia, Secchi, Maria Beatrice, Ghelfi, Davide, Anastasio, Luigi, Sofia, Lucia, Carbone, Maria, Cipollone, Francesco, Guagnano, Maria Teresa, Valeriani, Emanuele, Rossi, Ilaria, Mancuso, Gerardo, Calipari, Daniela, Bartone, Mose, Delitala, Giuseppe, Berria, Maria, Pes, Chiara, Delitala, Alessandro, Muscaritoli, Maurizio, Molfino, Alessio, Petrillo, Enrico, Zuccala, Giuseppe, D'Aurizio, Gabriella, Romanelli, Giuseppe, Marengoni, Alessandra, Zucchelli, Alberto, Manzoni, Francesca, Volpini, Andrea, Picardi, Antonio, Gentilucci, Umberto Vespasiani, Gallo, Paolo, Dell'Unto, Chiara, Annoni, Giorgio, Corsi, Maurizio, Bellelli, Giuseppe, Zazzetta, Sara, Mazzola, Paolo, Szabo, Hajnalka, Bonfanti, Alessandra, Arturi, Franco, Succurro, Elena, Rubino, Mariangela, Tassone, Bruno, Sesti, Giorgio, Serra, Maria Grazia, Bleve, Maria Antonietta, Gasbarrone, Laura, Sajeva, Maria Rosaria, Brucato, Antonio, Ghidoni, Silvia, Fabris, Fabrizio, Bertozzi, Irene, Bogoni, Giulia, Rabuini, Maria Victoria, Cosi, Elisabetta, Scarinzi, Paolo, Amabile, Annalisa, Omenetto, Elisabetta, Prandini, Tancredi, Manfredini, Roberto, Fabbian, Fabio, Boari, Benedetta, De Giorgi, Alfredo, Tiseo, Ruana, De Giorgio, Roberto, Paolisso, Giuseppe, Rizzo, Maria Rosaria, Borghi, Claudio, Strocchi, Enrico, Ianniello, Eugenia, Soldati, Mario, Sabba, Carlo, Vella, Francesco Saverio, Suppressa, Patrizia, Agosti, Pasquale, Schilardi, Andrea, Loparco, Francesca, De Vincenzo, Giovanni Michele, Comitangelo, Alessio, Amoruso, Emanuele, Fenoglio, Luigi, Falcetta, Andrea, Bracco, Christian, Fracanzani, Anna L., Fargion, Silvia, Tiraboschi, Silvia, Cespiati, Annalisa, Oberti, Giovanna, Sigon, Giordano, Peyvandi, Flora, Rossio, Raffaella, Ferrari, Barbara, Colombo, Giulia, Monzani, Valter, Savojardo, Valeria, Folli, Christian, Ceriani, Giuliana, Salerno, Francesco, Pallini, Giada, Dallegri, Franco, Ottonello, Luciano, Liberale, Luca, Caserza, Lara, Salam, Kassem, Liberato, Nicola Lucio, Tognin, Tiziana, Bianchi, Giovanni Battista, Giaquinto, Sabrina, Purrello, Francesco, Di Pino, Antonino, Piro, Salvatore, Rozzini, Renzo, Falanga, Lina, Spazzini, Elena, Ferrandina, Camillo, Montrucchio, Giuseppe, Petitti, Paolo, Peasso, Paolo, Favale, Edoardo, Poletto, Cesare, Salmi, Raffaella, Gaudenzi, Piergiorgio, Violi, Francesco, Perri, Ludovica, Landolfi, Raffaele, Montalto, Massimo, Mirijello, Antonio, Guasti, Luigina, Castiglioni, Luana, Maresca, Andrea, Squizzato, Alessandro, Campiotti, Leonardo, Grossi, Alessandra, Bertolotti, Marco, Mussi, Chiara, Lancellotti, Giulia, Libbra, Maria Vittoria, Dondi, Giulia, Pellegrini, Elisa, Carulli, Lucia, Galassi, Matteo, Grassi, Yasmine, Perticone, Maria, Battaglia, Rosa, Filice, Marco, Maio, Raffaele, Stanghellini, Vincenzo, Ruggeri, Eugenio, del Vecchio, Sara, Salvi, Andrea, Leonardi, Roberto, Damiani, Giampaolo, Capeci, William, Gabrielli, Armando, Mattioli, Massimo, Martino, Giuseppe Pio, Biondi, Lorenzo, Pettinari, Pietro, Ghio, Riccardo, Dal Col, Anna, Minisola, Salvatore, Colangelo, Luciano, Cilli, Mirella, Labbadia, Giancarlo, Afeltra, Antonella, Marigliano, Benedetta, Pipita, Maria Elena, Castellino, Pietro, Zanoli, Luca, Pignataro, Samuele, Gennaro, Alfio, Blanco, Julien, Saracco, Valter, Fogliati, Marisa, Bussolino, Carlo, Mete, Francesca, Gino, Miriam, Cittadini, Antonio, Vigorito, Carlo, Arcopinto, Michele, Salzano, Andrea, Bobbio, Emanuele, Marra, Alberto Maria, Sirico, Domenico, Moreo, Guido, Gasparini, Francesca, Prolo, Silvia, Pina, Gloria, Ballestrero, Alberto, Ferrando, Fabio, Berra, Sergio, Dassi, Simonetta, Nava, Maria Cristina, Graziella, Bruno, Baldassarre, Stefano, Fragapani, Salvatore, Gruden, Gabriella, Galanti, Giorgio, Mascherini, Gabriele, Petri, Cristian, Stefani, Laura, Girino, Margherita, Piccinelli, Valeria, Nasso, Francesco, Gioffre, Vincenza, Pasquale, Maria, Scattolin, Giuseppe, Martinelli, Sergio, Turrin, Mauro, Sechi, Leonardo, Catena, Cristina, Colussi, Gianluca, Passariello, Nicola, Rinaldi, Luca, Berti, Franco, Famularo, Giuseppe, Tarsitani, Patrizia, Castello, Roberto, Pasino, Michela, Ceda, Gian Paolo, Maggio, Marcello Giuseppe, Morganti, Simonetta, Artoni, Andrea, Del Giacco, Stefano, Firinu, Davide, Losa, Francesca, Paoletti, Giovanni, Costanzo, Giulia, Montalto, Giuseppe, Licata, Anna, Malerba, Valentina, Montalto, Filippo Alessandro, Lasco, Antonino, Basile, Giorgio, Catalano, Antonino, Malatino, Lorenzo, Stancanelli, Benedetta, Terranova, Valentina, Di Marca, Salvatore, Di Quattro, Rosario, La Malfa, Lara, Caruso, Rossella, Mecocci, Patrizia, Ruggiero, Carmelinda, Boccardi, Virginia, Meschi, Tiziana, Lauretani, Fulvio, Ticinesi, Andrea, Nouvenne, Antonio, Minuz, Pietro, Fondrieschi, Luigi, Pirisi, Mario, Fra, Gian Paolo, Sola, Daniele, Porta, Massimo, Riva, Piero, Quadri, Roberto, Larovere, Erica, Novelli, Marco, Scanzi, Giorgio, Mengoli, Caterina, Provini, Stella, Ricevuti, Laura, Simeone, Emilio, Scurti, Rosa, Tolloso, Fabio, Tarquini, Roberto, Valoriani, Alice, Dolenti, Silvia, Vannini, Giulia, Tedeschi, Alberto, Trotta, Lucia, Volpi, Riccardo, Bocchi, Pietro, Vignali, Alessandro, Harari, Sergio, Lonati, Chiara, Cattaneo, Mara, Napoli, Federico, Corrao, Salvatore, Argano, Christiano, Natoli, Giuseppe, Nobili, Alessandro, Corazza, Gino Roberto, Mannucci, Pier Mannuccio, Perticone, Francesco, and Rinaldi, Luca
Subjects: medicine.medical_specialty, Multivariate analysis, lcsh:Medicine, Socio-culturale, Disease, 030204 cardiovascular system & hematology, elderly, Article, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, 030212 general & internal medicine, Depression (differential diagnoses), Polypharmacy, business.industry, lcsh:R, General Medicine, medicine.disease, Comorbidity, elderly, sex profiles, disease distribution, in-hospital mortality, 3-month mortality, 1-year mortality, Mood disorders, disease distribution, 1-year mortality, 3-month mortality, sex profiles, business, in-hospital mortality, Kidney disease
Abstract: Background: The RePoSi study has provided data on comorbidities, polypharmacy, and sex dimorphism in hospitalised elderly patients. Methods: We retrospectively analysed data collected from the 2010, 2012, 2014, and 2016 data sets of the RePoSi register. The aim of this study was to explore the sex-differences and to validate the multivariate model in the entire dataset with an expanded follow-up at 1 year. Results: Among 4714 patients, 51% were women and 49% were men. The disease distribution showed that diabetes, coronary artery disease, chronic obstructive pulmonary disease, chronic kidney disease, and malignancy were more frequent in men but that hypertension, anaemia, osteoarthritis, depression, and diverticulitis disease were more common in women. Severity and comorbidity indexes according to the Cumulative Illness Rating Scale (CIRS-s and CIRS-c) were higher in men, while cognitive impairment, mood disorders, and disability in daily life measured by the Barthel Index (BI) were worse in women. In the multivariate analysis, BI, CIRS, and malignancy significantly increased the risk of death in men at the 1-year follow-up, while age was independently associated with mortality in women. Conclusions: Our study highlighted the relevance and the validity of our previous predictive model in the identification of sex dimorphism in hospitalised elderly patients underscoring the need of sex-personalised health-care.
Published: 2019

9. Prevalence, characteristics and treatment of chronic pain in elderly patients hospitalized in internal medicine wards

Author: Corsi, Nicole, Roberto, Anna, Cortesi, Laura, Nobili, Alessandro, Mannucci, Pier Mannuccio, Corli, Oscar, Prisco, Domenico, Silvestri, Elena, Emmi, Giacomo, Bettiol, Alessandra, Caterina, Cenci, Biolo, Gianni, Zanetti, Michela, Guadagni, Martina, Zaccari, Michele, Chiuch, Massimiliano, Vanoli, Massimo, Grignani, Giulia, Pulixi, Edoardo Alessandro, Bernardi, Mauro, Bassi, Silvia Li, Santi, Luca, Zaccherini, Giacomo, Lupattelli, Graziana, Mannarino, Elmo, Bianconi, Vanessa, Paciullo, Francesco, Alcidi, Riccardo, Nuti, Ranuccio, Valenti, Roberto, Ruvio, Martina, Cappelli, Silvia, Palazzuoli, Alberto, Girelli, Domenico, Busti, Fabiana, Marchi, Giacomo, Barbagallo, Mario, Dominguez, Ligia, Cocita, Floriana, Beneduce, Vincenza, Plances, Lidia, Corrao, Salvatore, Natoli, Giuseppe, Mularo, Salvatore, Raspanti, Massimo, Cavallaro, Federica, Zoli, Marco, Lazzari, Ilaria, Brunori, Mattia, Fabbri, Elisa, Magalotti, Donatella, Arno, Raffaella, Pasini, Franco Laghi, Capecchi, Pier Leopoldo, Palasciano, Giuseppe, Modeo, Maria Ester, Di Gennaro, Carla, Cappellini, Maria Domenica, Maira, Diletta, Di Stefano, Valeria, Fabio, Giovanna, Seghezzi, Sonia, Mancarella, Marta, De Amicis, Margherita Migone, De Luca, Giacomo, Scaramellini, Natalia, Cesari, Matteo, Rossi, Paolo Dionigi, Damanti, Sarah, Clerici, Marta, Conti, Federica, Bonini, Giulia, Ottolini, Barbara Brignolo, Di Sabatino, Antonio, Miceli, Emanuela, Lenti, Marco Vincenzo, Pisati, Martina, Dominioni, Costanza Caccia, Murialdo, Giovanni, Marra, Alessio, Cattaneo, Federico, Pontremoli, Roberto, Beccati, Valentina, Nobili, Giulia, Secchi, Maria Beatrice, Ghelfi, Davide, Anastasio, Luigi, Sofia, Lucia, Carbone, Maria, Cipollone, Francesco, Guagnano, Maria Teresa, Valeriani, Emanuele, Rossi, Ilaria, Mancuso, Gerardo, Calipari, Daniela, Bartone, Mose, Delitala, Giuseppe, Berria, Maria, Pes, Chiara, Delitala, Alessandro, Muscaritoli, Maurizio, Molfino, Alessio, Petrillo, Enrico, Zuccala, Giuseppe, D'Aurizio, Gabriella, Romanelli, Giuseppe, Marengoni, Alessandra, Zucchelli, Alberto, Manzoni, Francesca, Volpini, Andrea, Picardi, Antonio, Gentilucci, Umberto Vespasiani, Gallo, Paolo, Dell'Unto, Chiara, Annoni, Giorgio, Corsi, Maurizio, Bellelli, Giuseppe, Zazzetta, Sara, Mazzola, Paolo, Szabo, Hajnalka, Bonfanti, Alessandra, Arturi, Franco, Succurro, Elena, Rubino, Mariangela, Tassone, Bruno, Sesti, Giorgio, Serra, Maria Grazia, Bleve, Maria Antonietta, Gasbarrone, Laura, Sajeva, Maria Rosaria, Brucato, Antonio, Ghidoni, Silvia, Fabris, Fabrizio, Bertozzi, Irene, Bogoni, Giulia, Rabuini, Maria Victoria, Cosi, Elisabetta, Scarinzi, Paolo, Amabile, Annalisa, Omenetto, Elisabetta, Prandini, Tancredi, Manfredini, Roberto, Fabbian, Fabio, Boari, Benedetta, De Giorgi, Alfredo, Tiseo, Ruana, De Giorgio, Roberto, Paolisso, Giuseppe, Rizzo, Maria Rosaria, Borghi, Claudio, Strocchi, Enrico, Ianniello, Eugenia, Soldati, Mario, Sabba, Carlo, Vella, Francesco Saverio, Suppressa, Patrizia, Agosti, Pasquale, Schilardi, Andrea, Loparco, Francesca, De Vincenzo, Giovanni Michele, Comitangelo, Alessio, Amoruso, Emanuele, Fenoglio, Luigi, Falcetta, Andrea, Bracco, Christian, Fracanzani, Anna L., Fargion, Silvia, Tiraboschi, Silvia, Cespiati, Annalisa, Oberti, Giovanna, Sigon, Giordano, Peyvandi, Flora, Rossio, Raffaella, Ferrari, Barbara, Colombo, Giulia, Monzani, Valter, Savojardo, Valeria, Folli, Christian, Ceriani, Giuliana, Salerno, Francesco, Pallini, Giada, Dallegri, Franco, Ottonello, Luciano, Liberale, Luca, Caserza, Lara, Salam, Kassem, Liberato, Nicola Lucio, Tognin, Tiziana, Bianchi, Giovanni Battista, Giaquinto, Sabrina, Purrello, Francesco, Di Pino, Antonino, Piro, Salvatore, Rozzini, Renzo, Falanga, Lina, Spazzini, Elena, Ferrandina, Camillo, Montrucchio, Giuseppe, Petitti, Paolo, Peasso, Paolo, Favale, Edoardo, Poletto, Cesare, Salmi, Raffaella, Gaudenzi, Piergiorgio, Violi, Francesco, Perri, Ludovica, Landolfi, Raffaele, Montalto, Massimo, Mirijello, Antonio, Guasti, Luigina, Castiglioni, Luana, Maresca, Andrea, Squizzato, Alessandro, Campiotti, Leonardo, Grossi, Alessandra, Bertolotti, Marco, Mussi, Chiara, Lancellotti, Giulia, Libbra, Maria Vittoria, Dondi, Giulia, Pellegrini, Elisa, Carulli, Lucia, Galassi, Matteo, Grassi, Yasmine, Perticone, Francesco, Perticone, Maria, Battaglia, Rosa, Filice, Marco, Maio, Raffaele, Stanghellini, Vincenzo, Ruggeri, Eugenio, del Vecchio, Sara, Salvi, Andrea, Leonardi, Roberto, Damiani, Giampaolo, Capeci, William, Gabrielli, Armando, Mattioli, Massimo, Martino, Giuseppe Pio, Biondi, Lorenzo, Pettinari, Pietro, Ghio, Riccardo, Dal Col, Anna, Minisola, Salvatore, Colangelo, Luciano, Cilli, Mirella, Labbadia, Giancarlo, Afeltra, Antonella, Marigliano, Benedetta, Pipita, Maria Elena, Castellino, Pietro, Zanoli, Luca, Pignataro, Samuele, Gennaro, Alfio, Blanco, Julien, Saracco, Valter, Fogliati, Marisa, Bussolino, Carlo, Mete, Francesca, Gino, Miriam, Cittadini, Antonio, Vigorito, Carlo, Arcopinto, Michele, Salzano, Andrea, Bobbio, Emanuele, Marra, Alberto Maria, Sirico, Domenico, Moreo, Guido, Gasparini, Francesca, Prolo, Silvia, Pina, Gloria, Ballestrero, Alberto, Ferrando, Fabio, Berra, Sergio, Dassi, Simonetta, Nava, Maria Cristina, Graziella, Bruno, Baldassarre, Stefano, Fragapani, Salvatore, Gruden, Gabriella, Galanti, Giorgio, Mascherini, Gabriele, Petri, Cristian, Stefani, Laura, Girino, Margherita, Piccinelli, Valeria, Nasso, Francesco, Gioffre, Vincenza, Pasquale, Maria, Scattolin, Giuseppe, Martinelli, Sergio, Turrin, Mauro, Sechi, Leonardo, Catena, Cristina, Colussi, Gianluca, Passariello, Nicola, Rinaldi, Luca, Berti, Franco, Famularo, Giuseppe, Tarsitani, Patrizia, Castello, Roberto, Pasino, Michela, Ceda, Gian Paolo, Maggio, Marcello Giuseppe, Morganti, Simonetta, Artoni, Andrea, Del Giacco, Stefano, Firinu, Davide, Losa, Francesca, Paoletti, Giovanni, Costanzo, Giulia, Montalto, Giuseppe, Licata, Anna, Malerba, Valentina, Montalto, Filippo Alessandro, Lasco, Antonino, Basile, Giorgio, Catalano, Antonino, Malatino, Lorenzo, Stancanelli, Benedetta, Terranova, Valentina, Di Marca, Salvatore, Di Quattro, Rosario, La Malfa, Lara, Caruso, Rossella, Mecocci, Patrizia, Ruggiero, Carmelinda, Boccardi, Virginia, Meschi, Tiziana, Lauretani, Fulvio, Ticinesi, Andrea, Nouvenne, Antonio, Minuz, Pietro, Fondrieschi, Luigi, Pirisi, Mario, Fra, Gian Paolo, Sola, Daniele, Porta, Massimo, Riva, Piero, Quadri, Roberto, Larovere, Erica, Novelli, Marco, Scanzi, Giorgio, Mengoli, Caterina, Provini, Stella, Ricevuti, Laura, Simeone, Emilio, Scurti, Rosa, Tolloso, Fabio, Tarquini, Roberto, Valoriani, Alice, Dolenti, Silvia, Vannini, Giulia, Tedeschi, Alberto, Trotta, Lucia, Volpi, Riccardo, Bocchi, Pietro, Vignali, Alessandro, Harari, Sergio, Lonati, Chiara, Cattaneo, Mara, Duque Nieves, Ramirez, Molinero Alberto, Muela, Requejo Pedro, Abad, Pelaez Vanessa, Lopez, Lara, Tamargo, Viros Xavier, Corbella, Francesc, Formiga, Manglano Jesus, Diez, Tello Esperanza, Bejarano, Behamonte Esther, Del Corral, Puras Maria, Sevil, Romero, Manuel, Llorente Blanca, Pinilla, Gonzalez-Cobos Cristina, Lopez, Victoria, Villalba Garcia M., Saez, Lopez, Bosco, Juan, Baena Susana, Sanz, Gallego Marta, Arroyo, Becerra Concepcion, Gonzalez, Moyano Antonio, Fernandez, Gomez Hernandez, Mercedes, Poyato Borrego, Manuel, Cuadros Raquel, Pacheco, Rojas Florencia, Perez, Olid Beatriz, Garcia, Garcia Sara, Carrascosa, Cervellera Alfonso, Gonzalez-Cruz, Martinez Marta, Peinado, Cantero Alberto, Ruiz, Arraigosa Antonio, Albarracin, Guerrero Montserrat, Godoy, Miguel Angel, Baron Ramos, Jose Manuel, Machin, Veleiro Ignacio, Novo, Suarez Lucia, Alvela, Alfonso, Lopez, Bran David, Rubal, Vazquez Iria, Iniguez, and Prego Monica, Rios
Subjects: Male, medicine.medical_specialty, Aging, Pharmacological therapy, Undertreatment, Socio-culturale, Chronic pain, Comorbidity, Pharmacological treatment, 03 medical and health sciences, 0302 clinical medicine, Cognition, Aging, Analgesic treatment, Chronic pain, Pain management, Undertreatment, Internal medicine, medicine, Hospital discharge, 80 and over, Internal Medicine, Elderly people, Cognitive status, Humans, 030212 general & internal medicine, Registries, Depression (differential diagnoses), Aged, Aged, 80 and over, Analgesics, business.industry, Depression, Settore MED/09 - MEDICINA INTERNA, medicine.disease, Pain management, Logistic Models, Italy, Analgesic treatment, Spain, Chronic Pain, Female, Hospital Units, Multivariate Analysis, Pain Management, business, Hospital stay, 030217 neurology & neurosurgery
Abstract: Chronic pain is a frequent characteristic of elderly people and represents an actual and still poorly debated topic.We investigated pain prevalence and intensity, and its pharmacological therapy in elderly patients hospitalized in 101 internal medicine wards.Taking advantage of the "REgistro POliterapie Società Italiana Medicina Interna" (REPOSI), we collected 2535 patients of whom almost a quarter was older than 85 years old. Among them, 582 patients were affected by pain (either chronic or acute) and 296 were diagnosed with chronic pain.Patients with pain showed worse cognitive status, higher depression and comorbidities, and a longer duration of hospital stay compared to those without pain (all p .0366). Patients with chronic pain revealed lower level of independency in their daily life, worse cognitive status and higher level of depression compared to acute pain patients (all p .0156). Moreover, most of them were not treated for pain at admission (73.4%) and half of them was not treated with any analgesic drug at discharge (50.5%). This difference affected also the reported levels of pain intensity. Patients who received analgesics at both admission and discharge remained stable (p = .172). Conversely, those not treated at admission who received an analgesic treatment during the hospital stay decreased their perceived pain (p .0001).Our results show the need to focus more attention on the pharmacological treatment of chronic pain, especially in hospitalized elderly patients, in order to support them and facilitate their daily life after hospital discharge.
Published: 2018

10. Sex-related Differences in Systemic Sclerosis: A Multicenter Cross-sectional Study From the National Registry of the Italian Society for Rheumatology

Author: Rossella, De Angelis, Dilia, Giuggioli, Gianluigi, Bajocchi, Lorenzo, Dagna, Giovanni, Zanframundo, Rosario, Foti, Fabio, Cacciapaglia, Giovanna, Cuomo, Alarico, Ariani, Edoardo, Rosato, Serena, Guiducci, Francesco, Girelli, Valeria, Riccieri, Elisabetta, Zanatta, Silvia, Bosello, Ilaria, Cavazzana, Francesca, Ingegnoli, Maria De, Santis, Giuseppe, Murdaca, Giuseppina, Abignano, Nicoletta, Romeo, Alessandra, Della Rossa, Maurizio, Caminiti, Annamaria, Iuliano, Giovanni, Ciano, Lorenzo, Beretta, Gianluca, Bagnato, Ennio, Lubrano, Ilenia, De Andres, Alessandro, Giollo, Marta, Saracco, Cecilia, Agnes, Federica, Lumetti, Amelia, Spinella, Luca, Magnani, Corrado, Campochiaro, Giacomo, De Luca, Veronica, Codullo, Elisa, Visalli, Francesco, Masini, Antonietta, Gigante, Silvia, Bellando-Randone, Greta, Pellegrino, Erika, Pigatto, Francesca, Dall'Ara, Maria Grazia, Lazzaroni, Elena, Generali, Gianna, Mennillo, Simone, Barsotti, Giuseppa Pagano, Mariano, Francesca, Calabrese, Federica, Furini, Licia, Vultaggio, Simone, Parisi, Clara Lisa, Peroni, Anna Maria, Risa, Davide, Rozza, Anna, Zanetti, Greta, Carrara, Giampiero, Landolfi, Carlo Alberto, Scirè, Gerolamo, Bianchi, Enrico, Fusaro, Gian Domenico, Sebastiani, Marcello, Govoni, Salvatore, D'Angelo, Franco, Cozzi, Andrea, Doria, Florenzo, Iannone, Carlo, Salvarani, Marco, Matucci-Cerinic, Clodoveo, Ferri, De Angelis, R, Giuggioli, D, Bajocchi, G, Dagna, L, Zanframundo, G, Foti, R, Cacciapaglia, F, Cuomo, G, Ariani, A, Rosato, E, Guiducci, S, Girelli, F, Riccieri, V, Zanatta, E, Bosello, S, Cavazzana, I, Ingegnoli, F, Santis, M, Murdaca, G, Abignano, G, Romeo, N, Della Rossa, A, Caminiti, M, Iuliano, A, Ciano, G, Beretta, L, Bagnato, G, Lubrano, E, De Andres, I, Giollo, A, Saracco, M, Agnes, C, Lumetti, F, Spinella, A, Magnani, L, Campochiaro, C, De Luca, G, Codullo, V, Visalli, E, Masini, F, Gigante, A, Bellando-Randone, S, Pellegrino, G, Pigatto, E, Dall'Ara, F, Lazzaroni, M, Generali, E, Mennillo, G, Barsotti, S, Mariano, G, Calabrese, F, Furini, F, Vultaggio, L, Parisi, S, Peroni, C, Risa, A, Rozza, D, Zanetti, A, Carrara, G, Landolfi, G, Scire, C, Bianchi, G, Fusaro, E, Sebastiani, G, Govoni, M, D'Angelo, S, Cozzi, F, Doria, A, Iannone, F, Salvarani, C, Matucci-Cerinic, M, Ferri, C, de Angelis, R., Giuggioli, D., Bajocchi, G., Dagna, L., Zanframundo, G., Foti, R., Cacciapaglia, F., Cuomo, G., Ariani, A., Rosato, E., Guiducci, S., Girelli, F., Riccieri, V., Zanatta, E., Bosello, S., Cavazzana, I., Ingegnoli, F., de Santis, M., Murdaca, G., Abignano, G., Romeo, N., Rossa, A. D., Caminiti, M., Iuliano, A., Ciano, G., Beretta, L., Bagnato, G., Lubrano, E., de Andres, I., Giollo, A., Saracco, M., Agnes, C., Lumetti, F., Spinella, A., Magnani, L., Campochiaro, C., de Luca, Giacomo., Codullo, V., Visalli, E., Masini, F., Gigante, A., Bellando-Randone, S., Pellegrino, G., Pigatto, E., Dall'Ara, F., Lazzaroni, M. G., Generali, E., Mennillo, G., Barsotti, S., Mariano, G. P., Calabrese, F., Furini, F., Vultaggio, L., Parisi, S., Peroni, C. L., Risa, A. M., Rozza, D., Zanetti, A., Carrara, G., Landolfi, G., Scire, C. A., Bianchi, G., Fusaro, E., Sebastiani, G. D., Govoni, M., D'Angelo, S., Cozzi, F., Doria, A., Iannone, F., Salvarani, C., Matucci-Cerinic, M., Ferri, C., De Angelis, Rossella, Giuggioli, Dilia, Bajocchi, Gianluigi, Dagna, Lorenzo, Zanframundo, Giovanni, Foti, Rosario, Cacciapaglia, Fabio, Cuomo, Giovanna, Ariani, Alarico, Rosato, Edoardo, Guiducci, Serena, Girelli, Francesco, Riccieri, Valeria, Zanatta, Elisabetta, Bosello, Silvia, Cavazzana, Ilaria, Ingegnoli, Francesca, De Santis, Maria, Murdaca, Giuseppe, Abignano, Giuseppina, Romeo, Nicoletta, Della Rossa, Alessandra, Caminiti, Maurizio, Iuliano, Annamaria, Ciano, Giovanni, Beretta, Lorenzo, Bagnato, Gianluca, Lubrano, Ennio, De Andres, Ilenia, Giollo, Alessandro, Saracco, Marta, Agnes, Cecilia, Lumetti, Federica, Spinella, Amelia, Magnani, Luca, Campochiaro, Corrado, De Luca, Giacomo, Codullo, Veronica, Visalli, Elisa, Masini, Francesco, Gigante, Antonietta, Bellando-Randone, Silvia, Pellegrino, Greta, Pigatto, Erika, Dall'Ara, Francesca, Lazzaroni, Maria Grazia, Generali, Elena, Mennillo, Gianna, Barsotti, Simone, Pagano Mariano, Giuseppa, Calabrese, Francesca, Furini, Federica, Vultaggio, Licia, Parisi, Simone, Peroni, Clara Lisa, Risa, Anna Maria, Rozza, Davide, Zanetti, Anna, Carrara, Greta, Landolfi, Giampiero, Scirè, Carlo Alberto, Bianchi, Gerolamo, Fusaro, Enrico, Sebastiani, Gian Domenico, Govoni, Marcello, D'Angelo, Salvatore, Cozzi, Franco, Doria, Andrea, Iannone, Florenzo, Salvarani, Carlo, Matucci-Cerinic, Marco, and Ferri, Clodoveo
Subjects: Male, medicine.medical_specialty, Vital capacity, Settore MED/16 - REUMATOLOGIA, Cross-sectional study, Immunology, Left, Socio-culturale, scleroderma, sex, systemic sclerosis, Disease, Ventricular Function, Left, Scleroderma, Systemic sclerosi, Rheumatology, Internal medicine, Sicca syndrome, Sex, Systemic sclerosis, Cross-Sectional Studies, Female, Humans, Italy, Registries, Sex Characteristics, Stroke Volume, Scleroderma, Systemic, Sjogren's Syndrome, medicine, LS8_2, Immunology and Allergy, Ventricular Function, Honeycombing, skin and connective tissue diseases, Ejection fraction, integumentary system, business.industry, Systemic, medicine.disease, Cohort, business
Abstract: ObjectiveThere is still a great deal to learn about the influence of sex in systemic sclerosis (SSc). In this respect, national registries provide large and homogeneous patient cohorts for analytical studies. We therefore investigated a wide-ranging and well-characterized SSc series with the aim of identifying sex differences in disease expression, with a special focus on demographic, clinical, and serological characteristics.MethodsA multicenter SSc cohort of 2281 patients, including 247 men, was recruited in the Italian Systemic sclerosis PRogression INvestiGation (SPRING) registry. Demographic data, disease manifestations, serological profile, and internal organ involvement were compared.ResultsThe overall female/male ratio was 8.2:1. Female/male ratios for limited cutaneous SSc, diffuse cutaneous SSc, and SSc sine scleroderma subsets were 8.7:1, 4.9:1, and 10.7:1, respectively. A shorter time from onset of Raynaud phenomenon to SSc diagnosis, an increased prevalence of the diffuse cutaneous subset, renal crisis, and digital ulcers were found in males, whereas a significantly higher percentage of sicca syndrome, serum antinuclear antibodies, antiextractable nuclear antigens, anti-La/SSB, and anticentromere protein B was detected in the female group. Males exhibited lower left ventricular ejection fraction, as well as higher prevalence of conduction blocks, arrhythmias, ground glass, and honeycombing. Moreover, forced vital capacity and total lung capacity were medially lower in men than in women. Finally, males were more frequently treated with immunosuppressive drugs.ConclusionOur study further supports the presence of several sex-related differences in patients with SSc. These differences were pronounced in the severity of cutaneous, peripheral vascular, and cardiopulmonary involvement for male patients, whereas an increased prevalence of sicca syndrome and a specific autoantibody profile characterized the female sex.
Published: 2022

11. Spectrum of short-term inflammatory musculoskeletal manifestations after COVID-19 vaccine administration: a report of 66 cases

Author: Francesca Motta, Veronica Brusi, Corrado Campochiaro, Lorenzo Dagna, Enrico Fusaro, Ilenia Di Cola, Clodoveo Ferri, Fabio Cacciapaglia, Caterina Bruno, Rosario Foti, Riccardo Meliconi, Francesca Francioso, Felice Galluccio, Serena Guiducci, Vincenzo Raimondo, Jacopo Ciaffi, Annamaria Iagnocco, Giovanna Cuomo, Giacomo De Luca, Antonio Tavoni, Francesco Ursini, Roberto Giacomelli, Maria De Santis, Silvia Bilia, Piero Ruscitti, Salvatore D'Angelo, Florenzo Iannone, Domenico Olivo, Martina D'Onghia, Rossella De Angelis, Marcella Visentini, Luana Mancarella, E. Pigatto, Ursini, F., Ruscitti, P., Raimondo, V., De Angelis, R., Cacciapaglia, F., Pigatto, E., Olivo, D., Di Cola, I., Galluccio, F., Francioso, F., Foti, R., Tavoni, A., D'Angelo, S., Campochiaro, C., Motta, F., De Santis, M., Bilia, S., Bruno, C., DE LUCA, Giacomo, Visentini, M., Ciaffi, J., Mancarella, L., Brusi, V., D'Onghia, M., Cuomo, G., Fusaro, E., Dagna, L., Guiducci, S., Meliconi, R., Iannone, F., Iagnocco, A., Giacomelli, R., Ferri, C., Ursini, Francesco, Ruscitti, Piero, Raimondo, Vincenzo, De Angelis, Rossella, Cacciapaglia, Fabio, Pigatto, Erika, Olivo, Domenico, Di Cola, Ilenia, Galluccio, Felice, Francioso, Francesca, Foti, Rosario, Tavoni, Antonio, D'Angelo, Salvatore, Campochiaro, Corrado, Motta, Francesca, De Santis, Maria, Bilia, Silvia, Bruno, Caterina, De Luca, Giacomo, Visentini, Marcella, Ciaffi, Jacopo, Mancarella, Luana, Brusi, Veronica, D'Onghia, Martina, Cuomo, Giovanna, Fusaro, Enrico, Dagna, Lorenzo, Guiducci, Serena, Meliconi, Riccardo, Iannone, Florenzo, Iagnocco, Annamaria, Giacomelli, Roberto, Ferri, Clodoveo, Ursini, F, Ruscitti, P, Raimondo, V, De Angelis, R, Cacciapaglia, F, Pigatto, E, Olivo, D, Di Cola, I, Galluccio, F, Francioso, F, Foti, R, Tavoni, A, D'Angelo, S, Campochiaro, C, Motta, F, De Santis, M, Bilia, S, Bruno, C, De Luca, G, Visentini, M, Ciaffi, J, Mancarella, L, Brusi, V, D'Onghia, M, Cuomo, G, Fusaro, E, Dagna, L, Guiducci, S, Meliconi, R, Iannone, F, Iagnocco, A, Giacomelli, R, and Ferri, C
Subjects: Male, medicine.medical_specialty, COVID-19 Vaccines, Coronavirus disease 2019 (COVID-19), Immunology, Population, Arthritis, medicine.disease_cause, General Biochemistry, Genetics and Molecular Biology, polymyalgia rheumatica, Immune system, Rheumatology, Rheumatic Diseases, Pandemic, medicine, Immunology and Allergy, Humans, Musculoskeletal Diseases, Covid-19, arthritis, vaccination, Intensive care medicine, Adverse effect, education, education.field_of_study, business.industry, SARS-CoV-2, COVID-19, Female, Middle Aged, medicine.disease, Vaccination, arthriti, Molecular mimicry, business
Abstract: In the past months, mass vaccination represented the turning point of the global battle against the COVID-19 pandemic, an unprecedented challenge for physicians, healthcare professionals, health systems and pharmaceutical companies. More than 6 billion doses of vaccine have been administered to date, covering nearly 50% of the world’s population. Although the vaccination campaign is still thwarted by spread of fake news disseminated by a ubiquitous antivaxxer movement, accumulating real-life data1 confirm the favourable safety profile already demonstrated in phase III clinical trials.2 Despite the lack of a steady literature evidence,3 the potential role of vaccines in promoting autoimmunity continues to intrigue many researchers. The theoretical basis of this association relies on the possible molecular mimicry between macromolecular components of the vaccine and specific human proteins and the exuberant immune response elicited by adjuvants contained in vaccines.4 Adverse events (AEs) associated with COVID-19 vaccines are usually mild and mainly restricted to injection site reactions. Interestingly, among systemic AEs, arthralgia is one of the most common.2 To the best of our knowledge, only isolated cases5 of arthritis developed after COVID-19 …
Published: 2022

12. Efficacy of canakinumab as first-line biologic agent in adult-onset Still's disease

Author: Alessandro Tomelleri, Elena Baldissera, Corrado Campochiaro, Lorenzo Dagna, Giulio Cavalli, Giacomo De Luca, Charles A. Dinarello, Cavalli, Giulio, Tomelleri, Alessandro, De Luca, Giacomo, Campochiaro, Corrado, Dinarello, Charles A., Baldissera, Elena, Dagna, Loreno, and DE LUCA, Giacomo
Subjects: medicine.medical_specialty, Adult-onset Still's disease, Letter, lcsh:Diseases of the musculoskeletal system, First line, Still's disease, Immunology, MEDLINE, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], 03 medical and health sciences, Remission induction, 0302 clinical medicine, Rheumatology, Internal medicine, medicine, Immunology and Allergy, 030304 developmental biology, 030203 arthritis & rheumatology, 0303 health sciences, business.industry, Canakinumab, Monoclonal, lcsh:RC925-935, business, medicine.drug
Abstract: Contains fulltext : 202901.pdf (Publisher’s version ) (Open Access)
Published: 2019

13. Large-Vessel Vasculitides: Takayasu Arteritis and Giant Cell Arteritis

Author: Lorenzo Dagna, Giacomo De Luca, Giulio Cavalli, Cavalli G., De Luca Giacomo., Dagna L., Tshomba Y., Baccellieri D., Chiesa R, Cavalli, G., De Luca, Giacomo., and Dagna, Lorenzo.
Subjects: Aorta, Pathology, medicine.medical_specialty, Endothelium, business.industry, medicine.disease, Giant cell arteritis, Stenosis, medicine.anatomical_structure, medicine.artery, cardiovascular system, medicine, medicine.symptom, business, Vasculitis, Claudication, Artery, Rare disease
Abstract: Vasculitis is an inflammatory process affecting blood vessels. Based on the involvement of the endothelium or the wall of an artery or vein, the inflammatory process can cause thickening, weakening, stenosis, occlusion, aneurysmal dilation, and scarring of the vessel, limiting blood supply to tissues and leading to partial or complete organ failure. Vasculitides affecting large arteries include Takayasu arteritis (TA) and giant cell arteritis (GCA). TA is a rare disease, which is more commonly observed in parts of Asia and the Middle East and typically affects younger women. TA causes inflammation of the aorta and its main branches and may cause a broad spectrum of symptoms ranging from limb claudication to chest pain.
Published: 2019

14. Myocarditis: An Interleukin-1-Mediated Disease?

Author: Corrado Campochiaro, Giacomo De Luca, Lorenzo Dagna, Giulio Cavalli, Moreno Tresoldi, De Luca, Giacomo, Cavalli, Giulio, Campochiaro, Corrado, Tresoldi, Moreno, Dagna, Lorenzo, and DE LUCA, Giacomo
Subjects: 0301 basic medicine, lcsh:Immunologic diseases. Allergy, auto-inflammatory disease, Opinion, Myocarditis, Immunology, heart failure, Context (language use), Inflammation, Disease, 030204 cardiovascular system & hematology, Sudden death, Anti-Cytokine Therapy, 03 medical and health sciences, 0302 clinical medicine, Fibrosis, medicine, Immunology and Allergy, auto-inflammatory diseases, business.industry, autoimmune myocarditi, Dilated cardiomyopathy, medicine.disease, autoimmune myocarditis, 030104 developmental biology, anti-cytokine therapy, medicine.symptom, business, lcsh:RC581-607, interleukin-1
Abstract: Myocarditis is defined by WHO as an inflammatory disease affecting the myocardium, diagnosed by endomyocardial biopsy (EMB) using established histological, immunological, and immunohistochemical criteria; it may be idiopathic, infectious, or autoimmune (1–4). A wide variety of histological myocarditis patterns have been described according to the diverse etiologies and to the stage of the disease at the time of EMB ascertainment. Viral infections represent the most common cause in Europe and North America (5). Different viral genomes can be detected in the myocardium of patients with myocarditis and dilated cardiomyopathy (DCM) using molecular techniques (6–14). When no infectious agents are identified on EMB and other known causes are excluded, autoimmune myocarditis (AMy) is the presumed etiology (15). These so-called “autoimmune myocarditis” or “virus-negative myocarditis” may occur as a distinct disease with exclusive cardiac involvement, or in the context of systemic autoimmune or inflammatory disorders with extracardiac involvement (5, 16–23). It is likely that several etiologic types of myocarditis confluence in a common immune-mediated pathogenic process leading to chronic inflammation and tissue damage. Irrespective of triggering agents, acute inflammation may progress to subacute and chronic stages and eventually result in tissue remodeling, fibrosis, contractile dysfunction, and finally DCM (4, 6, 8, 24–29). Besides contractile dysfunction, both early myocardial inflammation and late fibrotic changes play a critical role in the development of the arrhythmic burden, which makes myocarditis one of the leading causes of sudden death (19, 27–31). Clearly, treatment interventions effectively curbing the acute inflammatory process at an early stage can prevent late cardiac remodeling and improve patient’s outcome. Emerging evidence on the pathogenic mechanisms underlying cardiac inflammation is paving the way to novel, promising treatment strategies for myocarditis.
Published: 2018

15. Canakinumab injection for the treatment of active Still’s disease, including adult-onset Still’s disease

Author: Giulio Cavalli, Lorenzo Dagna, Nicola Farina, Alessandro Tomelleri, Corrado Campochiaro, Giacomo De Luca, Tomelleri, A., Campochiaro, C., De Luca, Giacomo., Farina, N., Cavalli, G., and Dagna, L.
Subjects: Adult-onset Still's disease, systemic juvenile idiopathic arthritis, Still's disease, Arthritis, Disease, canakinumab, 03 medical and health sciences, 0302 clinical medicine, medicine, Juvenile, Pharmacology (medical), Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Still’s disease, business.industry, Health Policy, Interleukin, medicine.disease, adult onset still’s disease, Canakinumab, 030220 oncology & carcinogenesis, Macrophage activation syndrome, Immunology, aosd, business, interleukin-1, macrophage activation syndrome, 030217 neurology & neurosurgery, medicine.drug
Abstract: Introduction: Still’s disease is a systemic, non-monogenic autoinflammatory condition affecting both children and adolescents (systemic juvenile idiopathic arthritis, sJIA) and adults (adult-onset Still’s disease, AOSD). Its clinical spectrum ranges from mild forms to life-threatening cases. Glucocorticoids represent the first-line therapy, but their chronic use is burdened with significant side effects. Hence, add-on therapy with disease modifying anti-rheumatic drugs and biologic anti-cytokine agents is frequently required, especially in patients with severe and recalcitrant clinical phenotypes. Among the targetable cytokines with a primary role in the pathogenesis of Still’s disease, interleukin-1 has a leading position. Areas covered: This review presents the available controlled evidence and observational studies regarding the efficacy and safety of canakinumab, a monoclonal antibody targeting interleukin-1β, in the treatment of Still’s disease. Expert opinion: Controlled studies fully support the clinical efficacy of canakinumab in the treatment of patients affected by sJIA. Conversely, strong evidences are still lacking in AOSD patients; nevertheless, its use in the adult population is legitimated by an increasing number of cases series and case reports and by preclinical data linking the pathogenesis of these two diseases. In addition, canakinumab has an excellent safety profile. Its role in preventing and treating macrophage activation syndrome is still debated.
Published: 2021

16. Hybrid FDG-PET/MR or FDG-PET/CT to Detect Disease Activity in Patients With Persisting Arrhythmias After Myocarditis

Author: Elena Busnardo, Giovanni Peretto, Cristina Basso, Anna Palmisano, Francesco De Cobelli, Alessandro Del Maschio, Antonio Esposito, Paola Ferro, Corrado Campochiaro, Claudia Calcagno, Giacomo De Luca, Simone Sala, Davide Vignale, Palmisano, Anna, Vignale, Davide, Peretto, Giovanni, Busnardo, Elena, Calcagno, Claudia, Campochiaro, Corrado, De Luca, Giacomo, Sala, Simone, Ferro, Paola, Basso, Cristina, Del Maschio, Alessandro, De Cobelli, Francesco, and Esposito, Antonio
Subjects: medicine.medical_specialty, Myocarditis, Inflammation, 030204 cardiovascular system & hematology, 030218 nuclear medicine & medical imaging, Disease activity, 03 medical and health sciences, 0302 clinical medicine, Fluorodeoxyglucose F18, Predictive Value of Tests, hybrid imaging, Positron Emission Tomography Computed Tomography, Humans, Medicine, Radiology, Nuclear Medicine and imaging, In patient, Late enhancement, business.industry, PET-MR, late enhancement, Myocardial inflammation, Arrhythmias, Cardiac, medicine.disease, Magnetic Resonance Imaging, Positron-Emission Tomography, Fdg pet ct, Radiology, Radiopharmaceuticals, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract: In myocarditis patients, persisting inflammation is associated with arrhythmias and unfavorable remodeling ([1][1]). Novel therapeutic strategies may counteract chronic myocardial inflammation, but their use is strictly dependent on the ability to detect and monitor myocardial inflammation.
Published: 2021

17. Systemic sclerosis myocarditis has unique clinical, histological and prognostic features: a comparative histological analysis

Author: Silvia Sartorelli, Anna Palmisano, Cristina Basso, Elisa Gremese, Antonio Esposito, Giacomo De Luca, Simone Sala, Stefania Rizzo, Carlo Selmi, Lorenzo Dagna, Maria De Santis, Corrado Campochiaro, Giovanni Peretto, Paolo Della Bella, Enrico De Lorenzis, G. Canestrari, S. L. Bosello, Gaetano Thiene, De Luca, G., Campochiaro, C., De Santis, M., Sartorelli, S., Peretto, G., Sala, S., Canestrari, G., De Lorenzis, E., Basso, C., Rizzo, S., Thiene, G., Palmisano, A., Esposito, A., Selmi, C., Gremese, E., Della Bella, P., Dagna, L., Bosello, S. L., and DE LUCA, Giacomo
Subjects: Male, medicine.medical_specialty, Settore MED/16 - REUMATOLOGIA, Myocarditis, systemic sclerosis, Biopsy, endomyocardial biopsy, heart failure, myocardial fibrosis, myocarditis, Magnetic Resonance Imaging, Cine, 030204 cardiovascular system & hematology, Systemic scleroderma, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Fibrosis, Internal medicine, medicine, Humans, Pharmacology (medical), Retrospective Studies, 030203 arthritis & rheumatology, Scleroderma, Systemic, medicine.diagnostic_test, business.industry, Myocardium, Retrospective cohort study, Middle Aged, Prognosis, medicine.disease, Dyspnea, Echocardiography, Heart failure, Electrocardiography, Ambulatory, Cardiology, Female, Myocardial fibrosis, business, Complication, Immunosuppressive Agents
Abstract: Objective To outline the clinical, histological and prognostic features of systemic sclerosis (SSc) endomyocardial biopsy-proven myocarditis with respect to those of diverse endomyocardial biopsy-proven virus-negative myocarditis (VNM). Methods We retrospectively analysed data from three cohorts of endomyocardial biopsy-proven myocarditis: SSc-related VNM (SSc-VNM); isolated VNM (i-VNM); and VNM related to other systemic autoimmune diseases (a-VNM). The degree of myocardial fibrosis was expressed as relative percentage and fibrotic score (0–3). Clinical data, cardiac enzymes, echocardiogram, 24 h ECG Holter and cardiac magnetic resonance were obtained at baseline and during follow-up. Non-parametric tests were used. Results We enrolled 12 SSc-VNM [11 females, mean age 49.3 (14.2) years; seven diffuse-SSc, five early-SSc], 12 i-VNM [12 females, mean age 47.7 (10.8) years] and 10 a-VNM [four females, mean age 48.4 (16.3) years] patients. SSc patients had higher degrees of myocardial fibrosis as assessed by both percentage [SSc-VNM: 44.8 (18.8)%; a-VNM: 28.6 (16.5)%; i-VNM: 24.9 (10.3)%; P = 0.019] and score [SSc-VNM: 2.3 (0.8); a-VNM: 1.4 (1.1); i-VNM: 1.2 (0.7); P = 0.002]. Myocardial fibrosis directly correlated with skin score (r = 0.625, P = 0.03) and number of ventricular ectopic beats on 24 h ECG Holter in SSc patients (r = 0.756, P = 0.01). Dyspnoea class was higher at presentation in SSc-VNM patients (P = 0.041) and we found heart failure only in SSc patients (25%) (P = 0.05). At cardiac magnetic resonance, myocardial oedema was nearly undetectable in SSc-VNM patients compared with others (P = 0.02). All patients received immunosuppressive treatment. The number of patients who died during follow-up due to cardiac complications was significantly higher in SSc-VNM patients (50%), as compared with a-VNM (0%) and i-VNM (8.3%) patients (P = 0.006). Patients who died during follow-up had higher degrees of myocardial fibrosis [52.2 (11.6)% vs 27.5 (12.9)%, P = 0.024; fibrotic score: 2.83 (0.41) vs 1.4 (0.9), P Conclusion SSc has unique clinical and histological features, as it tends to present more frequently with heart failure and a higher dyspnoea class and to show higher degrees of myocardial fibrosis. These specific features are paralleled by a worse cardiac prognosis.
Published: 2020

18. Primary systemic sclerosis heart involvement: A systematic literature review and preliminary data-driven, consensus-based WSF/HFA definition

Author: Cosimo Bruni, Maya H Buch, Daniel E Furst, Giacomo De Luca, Aleksandra Djokovic, Raluca B Dumitru, Alessandro Giollo, Marija Polovina, Alexia Steelandt, Kostantinos Bratis, Yossra Atef Suliman, Ivan Milinkovic, Anna Baritussio, Ghadeer Hasan, Anastasia Xintarakou, Yohei Isomura, George Markousis-Mavrogenis, Lorenzo Tofani, Sophie Mavrogeni, Luna Gargani, Alida LP Caforio, Carsten Tschöpe, Arsen Ristic, Karin Klingel, Sven Plein, Elijah R Behr, Yannick Allanore, Masataka Kuwana, Christopher P Denton, Dinesh Khanna, Thomas Krieg, Renzo Marcolongo, Ilaria Galetti, Elisabetta Zanatta, Francesco Tona, Petar Seferovic, Marco Matucci-Cerinic, Bruni, C., Buch, M. H., Furst, D. E., DE LUCA, Giacomo, Djokovic, A., Dumitru, R. B., Giollo, A., Polovina, M., Steelandt, A., Bratis, K., Suliman, Y. A., Milinkovic, I., Baritussio, A., Hasan, G., Xintarakou, A., Isomura, Y., Markousis-Mavrogenis, G., Tofani, L., Mavrogeni, S., Gargani, L., Caforio, A. L. P., Tschope, C., Ristic, A., Klingel, K., Plein, S., Behr, E. R., Allanore, Y., Kuwana, M., Denton, C. P., Khanna, D., Krieg, T., Marcolongo, R., Galetti, I., Zanatta, E., Tona, F., Seferovic, P., and Matucci-Cerinic, M.
Subjects: medicine.medical_specialty, Primary (chemistry), business.industry, Immunology, Original Manuscript, heart, Systematic review, Rheumatology, cardiac involvement, Immunology and Allergy, Medicine, definition, Systemic sclerosis, business, Intensive care medicine
Abstract: Introduction: Primary heart involvement in systemic sclerosis may cause morpho-functional and electrical cardiac abnormalities and is a common cause of death. The absence of a clear definition of primary heart involvement in systemic sclerosis limits our understanding and ability to focus on clinical research. We aimed to create an expert consensus definition for primary heart involvement in systemic sclerosis. Methods: A systematic literature review of cardiac involvement and manifestations in systemic sclerosis was conducted to inform an international and multi-disciplinary task force. In addition, the nominal group technique was used to derive a definition that was then subject to voting. A total of 16 clinical cases were evaluated to test face validity, feasibility, reliability and criterion validity of the newly created definition. Results: In total, 171 publications met eligibility criteria. Using the nominal group technique, experts added their opinion, provided statements to consider and ranked them to create the consensus definition, which received 100% agreement on face validity. A median 60(5–300) seconds was taken for the feasibility on a single case. Inter-rater agreement was moderate (mKappa (95% CI) = 0.56 (0.46–1.00) for the first round and 0.55 (0.44–1.00) for the second round) and intra-rater agreement was good (mKappa (95% CI) = 0.77 (0.47–1.00)). Criterion validity showed a 78 (73–84)% correctness versus gold standard. Conclusion: A preliminary primary heart involvement in systemic sclerosis consensus-based definition was created and partially validated, for use in future clinical research.
Published: 2022

19. The role of chest CT in deciphering interstitial lung involvement: systemic sclerosis versus COVID-19

Author: Jelena Blagojevic, Francesca Wanda Rossi, Alessandro Bartoloni, Cosimo Nardi, S. Tomassetti, Martina Orlandi, Alberto Moggi-Pignone, Yannick Allanore, L. Dagna, Stefano Palmucci, Carlo Vancheri, Marco Matucci-Cerinic, Francesca Della Casa, Marco Confalonieri, Federico Lavorini, Amato de Paulis, Lorenzo Tofani, Gloria Taliani, Virginia Vegni, Dinesh Khanna, Vittorio Miele, Alberto Pesci, Barbara Ruaro, C. Campochiaro, Lorenzo Zammarchi, Giovanni Morana, Michele Spinicci, Gianluca Sambataro, Antonella Caminati, Silvia Bellando-Randone, Daniela Melchiorre, Cosimo Bruni, Nicholas Landini, Francesco De Cobelli, Masataka Kuwana, Giacomo De Luca, Sergio Harari, Stefano Colagrande, Fabio Melchiorre, Edoardo Cavigli, Serena Guiducci, Christopher P. Denton, Fabrizio Luppi, Michael Hughes, Marco Albanesi, Orlandi, Martina, Landini, Nichola, Sambataro, Gianluca, Nardi, Cosimo, Tofani, Lorenzo, Bruni, Cosimo, Bellando-Randone, Silvia, Blagojevic, Jelena, Melchiorre, Daniela, Hughes, Michael, Denton, Christopher P, Luppi, Fabrizio, Ruaro, Barbara, Della Casa, Francesca, Rossi, Francesca W, De Luca, Giacomo, Campochiaro, Corrado, Spinicci, Michele, Zammarchi, Lorenzo, Tomassetti, Sara, Caminati, Antonella, Cavigli, Edoardo, Albanesi, Marco, Melchiorre, Fabio, Palmucci, Stefano, Vegni, Virginia, Guiducci, Serena, Moggi-Pignone, Alberto, Allanore, Yannick, Bartoloni, Alessandro, Confalonieri, Marco, Dagna, Lorenzo, De Cobelli, Francesco, De Paulis, Amato, Harari, Sergio, Khanna, Dinesh, Kuwana, Masataka, Taliani, Gloria, Lavorini, Federico, Miele, Vittorio, Morana, Giovanni, Pesci, Alberto, Vancheri, Carlo, Colagrande, Stefano, Matucci-Cerinic, Marco, Denton, Christopher P., Rossi, Francesca W., Decobelli, Francesco, Depaulis, Amato, Orlandi, M, Landini, N, Sambataro, G, Nardi, C, Tofani, L, Bruni, C, Bellando-Randone, S, Blagojevic, J, Melchiorre, D, Hughes, M, Denton, C, Luppi, F, Ruaro, B, Della Casa, F, Rossi, F, De Luca, G, Campochiaro, C, Spinicci, M, Zammarchi, L, Tomassetti, S, Caminati, A, Cavigli, E, Albanesi, M, Melchiorre, F, Palmucci, S, Vegni, V, Guiducci, S, Moggi-Pignone, A, Allanore, Y, Bartoloni, A, Confalonieri, M, Dagna, L, De Cobelli, F, De Paulis, A, Harari, S, Khanna, D, Kuwana, M, Taliani, G, Lavorini, F, Miele, V, Morana, G, Pesci, A, Vancheri, C, Colagrande, S, Matucci-Cerinic, M, Orlandi, M., Landini, N., Sambataro, G., Nardi, C., Tofani, L., Bruni, C., Bellando-Randone, S., Blagojevic, J., Melchiorre, D., Hughes, M., Denton, C. P., Luppi, F., Ruaro, B., Della Casa, F., Rossi, F. W., De Luca, G., Campochiaro, C., Spinicci, M., Zammarchi, L., Tomassetti, S., Caminati, A., Cavigli, E., Albanesi, M., Melchiorre, F., Palmucci, S., Vegni, V., Guiducci, S., Moggi-Pignone, A., Allanore, Y., Bartoloni, A., Confalonieri, M., Dagna, L., Decobelli, F., de Paulis, A., Harari, S., Khanna, D., Kuwana, M., Taliani, G., Lavorini, F., Miele, V., Morana, G., Pesci, A., Vancheri, C., Colagrande, S., and Matucci-Cerinic, M.
Subjects: medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Fibrosi, systemic sclerosis, education, Chest ct, Stock options, COVID-19, COVID-19 pneumonia, interstitial lung disease, lung CT scan, Computed tomography, Institutional ethics, COVID-19 Testing, Rheumatology, Fibrosis, Medicine, Humans, Pharmacology (medical), Lung, health care economics and organizations, Scleroderma, Systemic, Competing interests, medicine.diagnostic_test, business.industry, Interstitial lung disease, medicine.disease, Lung involvement, Peripheral, Clinical Practice, Pneumonia, Family medicine, Radiology, Differential diagnosis, business, Lung Diseases, Interstitial, Tomography, X-Ray Computed, systemic sclerosi, Human
Abstract: Background: In clinical practice, the striking similarities observed at computed tomography (CT) between the diseases make it difficult to distinguish a COVID-19 pneumonia from a progression of interstitial lung disease (ILD) secondary to Systemic sclerosis (SSc). The aim of the present study was to identify the main CT features that may help distinguishing SSc-ILD from COVID-19 pneumonia. Methods: This multicentric study included 22 international readers divided in the radiologist group (RAD) and non-radiologist group (nRAD). A total of 99 patients, 52 with COVID-19 and 47 with SSc-ILD, were included in the study. Findings: Fibrosis inside focal ground glass opacities (GGO) in the upper lobes; fibrosis in the lower lobe GGO; reticulations in lower lobes (especially if bilateral and symmetrical or associated with signs of fibrosis) were the CT features most frequently associated with SSc-ILD. The CT features most frequently associated with COVID- 19 pneumonia were: consolidation (CONS) in the lower lobes, CONS with peripheral (both central/peripheral or patchy distributions), anterior and posterior CONS and rounded-shaped GGOs in the lower lobes. After multivariate analysis, the presence of CONS in the lower lobes (p
Published: 2022

20. Cardiac immune-related adverse events: an immune-cardio-oncology puzzle

Author: Corrado Campochiaro, Giacomo De Luca, Lorenzo Dagna, Campochiaro, C., De Luca, Giacomo., and Dagna, L.
Subjects: Heart Failure, medicine.medical_specialty, business.industry, MEDLINE, medicine.disease, Medical Oncology, Immune system, Heart failure, Neoplasms, medicine, Humans, Cardio oncology, Cardiology and Cardiovascular Medicine, Adverse effect, Intensive care medicine, business
Published: 2021

21. Patient-reported outcome instruments in clinical trials of systemic sclerosis

Author: Joana Caetano, Corrado Campochiaro, Dinesh Khanna, Ana Maria Gheorghiu, Giacomo De Luca, John D Pauling, Maria Grazia Lazzaroni, Pauling, J. D., Caetano, J., Campochiaro, C., De Luca, Giacomo., Gheorghiu, A. M., Lazzaroni, M. G., and Khanna, D.
Subjects: 030203 arthritis & rheumatology, clinical trials, medicine.medical_specialty, Raynaud’s phenomenon, systemic sclerosis, business.industry, Immunology, Outcome measures, Reviews, Patient-reported outcome instruments, Outcome (game theory), Complement (complexity), Clinical trial, outcome measures, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, medicine, Immunology and Allergy, Patient-reported outcome, 030212 general & internal medicine, Intensive care medicine, business
Abstract: Patient-reported outcome instruments provide valuable insight into disease-related morbidity known only to the patient and complement more objective outcome tools in the clinical trial setting. They are of particular importance in systemic sclerosis owing to the challenges around defining disease activity, the episodic nature of many disease-specific manifestations and the paucity of validated objective surrogate outcome measures for use in clinical trials. Early clinical trials of systemic sclerosis often incorporated legacy patient-reported outcome instruments, but the last 20 years has witnessed the emergence of several scleroderma-specific instruments that are now being routinely used alongside other outcomes in systemic sclerosis clinical trials. More recently, the value of patient-reported outcomes has been highlighted by their prominence in the American College of Rheumatology Combined Response Index for Systemic Sclerosis that has been utilized as the primary endpoint of recent clinical trials of early diffuse systemic sclerosis. This review considers the role and performance of the various patient-reported outcome instruments utilized in systemic sclerosis clinical trials, the current positioning of patient-reported outcome instruments within clinical trial endpoint models across the range of systemic sclerosis disease manifestations and, where applicable, we shall highlight areas for future research.
Published: 2019

22. Interleukin-1 and Systemic Sclerosis: Getting to the Heart of Cardiac Involvement

Author: Giacomo De Luca, Giulio Cavalli, Corrado Campochiaro, Cosimo Bruni, Alessandro Tomelleri, Lorenzo Dagna, Marco Matucci-Cerinic, De Luca, Giacomo., Cavalli, G., Campochiaro, C., Bruni, C., Tomelleri, A., Dagna, L., and Matucci-Cerinic, M.
Subjects: lcsh:Immunologic diseases. Allergy, 0301 basic medicine, Heart Diseases, Inflammasomes, medicine.medical_treatment, Immunology, Inflammation, 030204 cardiovascular system & hematology, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, inflammasome, Fibrosis, medicine, Humans, Immunology and Allergy, Molecular Targeted Therapy, Scleroderma, Systemic, integumentary system, business.industry, Disease Management, Interleukin, Inflammasome, heart inflammation, medicine.disease, Connective tissue disease, systemic sclerosis (scleroderma), 030104 developmental biology, Cytokine, Perspective, Cytokines, Myocardial fibrosis, Disease Susceptibility, Inflammation Mediators, medicine.symptom, Energy Metabolism, lcsh:RC581-607, business, interleukin-1, cellular metabolism, Signal Transduction, medicine.drug
Abstract: Systemic sclerosis (SSc) is rare, severe connective tissue disease characterized by endothelial and vascular damage, immune activation, and resulting in inflammation and fibrosis of skin and internal organs, including the heart. SSc is associated with high morbidity and mortality. Cardiac involvement is frequent in SSc patients, even though often asymptomatic at early stages, and represents one of the major causes of SSc-related mortality. Heart involvement has a variable clinical presentation, and its pathogenesis is not completely understood. Myocardial fibrosis is traditionally considered the immunopathologic hallmark of heart involvement in SSc. This unique histological feature is paralleled by distinctive clinical and prognostic features. The so-called “vascular hypothesis” represents the most credited hypothesis to explain myocardial fibrosis. More recently, the prominent role of an inflammatory myocardial process has been identified as a cardinal event in the evolution to fibrosis, thus also delineating an “inflammation-driven pathway to fibrosis”. The pro-inflammatory cytokine interleukin (IL)-1 has an apical and cardinal role in the myocardial inflammatory cascade and in cardiac dysfunction. The primary aim of this perspective article is: to present the emerging evidence on the role of IL-1 and inflammasome in both SSc and heart inflammation, to review the complex interplay between cellular metabolism and inflammasome activation, and to discuss the rationale for targeted inhibition of IL-1 for the treatment of SSc-heart involvement, providing preliminary experimental and clinical data to support this hypothesis.
Published: 2021

23. Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial

Author: François-Xavier Lescure, Hitoshi Honda, Robert A Fowler, Jennifer Sloane Lazar, Genming Shi, Peter Wung, Naimish Patel, Owen Hagino, Ignacio J. Bazzalo, Marcelo M. Casas, Sebastián A. Nuñez, Yael Pere, Carlos M. Ibarrola, Marco A. Solis Aramayo, Maria C. Cuesta, Andrea E. Duarte, Pablo M. Gutierrez Fernandez, Maria A. Iannantuono, Erica A. Miyazaki, Javier P. Silvio, Dario G. Scublinsky, Alessandra Bales, Daniela Catarino, Elie Fiss, Sara Mohrbacher, Victor Sato, Antonio Baylao, Adilson Cavalcante, Francini Correa, Celso A. de Andrade, Juvencio Furtado, Nelson Ribeiro Filho, Valéria Telles, Leopoldo T. Trevelin, Ricardo Vipich, Rodrigo Boldo, Paula Borges, Suzana Lobo, Graziela Luckemeyer, Luana Machado, Maysa B. Alves, Ana C. Iglessias, Marianna M. Lago, Daniel W. Santos, Hugo Chapdelaine, Emilia L. Falcone, Rahima Jamal, Me-Linh Luong, Madeleine Durand, Stephane Doucet, François-Martin Carrier, Bryan A. Coburn, Lorenzo Del Sorbo, Sharon L. Walmsley, Sara Belga, Luke Y. Chen, Allison D. Mah, Theodore Steiner, Alissa J. Wright, J. Hajek, Neill Adhikari, Robert A. Fowler, Nick Daneman, Kosar A. Khwaja, Jason Shahin, Carolina Gonzalez, Rafael Silva, Marcelo Lindh, Gabriel Maluenda, Patricia Fernandez, Maite Oyonarte, Martin Lasso, Alexandre Boyer, Didier Bronnimann, Hoang-Nam Bui, Charles Cazanave, Helene Chaussade, Arnaud Desclaux, Mailys Ducours, Alexandre Duvignaud, Denis Malvy, Lisa Martin, Didier Neau, Duc Nguyen, Thierry Pistone, Gaetane Soubrane-Wirth, Julie Leitao, Clotilde Allavena, Charlotte Biron, Sabelline Bouchez, Benjamin Gaborit, Antoine Gregoire, Paul Le Turnier, Anne-Sophie Lecompte, Raphael Lecomte, Maeva Lefebvre, Francois Raffi, David Boutoille, Pascale H. Morineau, Romain Guéry, Emmanuel Chatelus, Nathalie Dumoussaud, Renaud Felten, Florina Luca, Bernard Goichot, Francis Schneider, Marie-Caroline Taquet, Matthieu Groh, Mathilde Roumier, Mathilde Neuville, Antoine Bachelard, Valentina Isernia, F-Xavier Lescure, Bao-Chau Phung, Anne Rachline, Aurelie Sautereau, Dorothee Vallois, Yves Bleher, Delphine Boucher, Clémentine Coudon, Jean Esnault, Thomas Guimard, Sophie Leautez-Nainville, Dominique Merrien, Marine Morrier, Pauline Motte-Vincent, Romain Gabeff, Hélène Leclerc, Céline Cozic, Romain Decours, Ronan Février, Gwenhael Colin, Sophie Abgrall, Dorothee Vignes, Raluca Sterpu, Mira Kuellmar, Melanie Meersch-Dini, Raphael Weiss, Alexander Zarbock, Christiane Antony, Marc Berger, Thorsten Brenner, Christian Taube, Frank Herbstreit, Sebastian Dolff, Margarethe Konik, Karsten Schmidt, Markus Zettler, Oliver Witzke, Boris Boell, Jorge Garcia Borrega, Philipp Koehler, Thomas Zander, Fabian Dusse, Othman Al-Sawaf, Philipp Köhler, Dennis Eichenauer, Matthias Kochanek, Alexander Shimabukuro-Vornhagen, Sibylle Mellinghoff, Annika Claßen, Jan-Michel Heger, Charlotte Meyer-Schwickerath, Paul Liedgens, Katrin Heindel, Ana Belkin, Asaf Biber, Mayan Gilboa, Itzchak Levy, Vladislav Litachevsky, Galia Rahav, Anat Finesod Wiedner, Tal Zilberman-Daniels, Yonatan Oster, Jacob Strahilevitz, Sigal Sviri, Elena M. Baldissera, Corrado Campochiaro, Giulio Cavalli, Lorenzo Dagna, Giacomo De Luca, Emanuel Della Torre, Alessandro Tomelleri, Davide Bernasconi De Luca, Amedeo F. Capetti, Massimo Coen, Maria V. Cossu, Massimo Galli, Andrea Giacomelli, Guido A. Gubertini, Stefano Rusconi, Giulia J. Burastero, Margherita Digaetano, Giovanni Guaraldi, Marianna Meschiari, Cristina Mussini, Cinzia Puzzolante, Sara Volpi, Marina Aiello, Alarico Ariani, Alfredo A. Chetta, Annalisa Frizzelli, Andrea Ticinesi, Domenico Tuttolomondo, Stefano Aliberti, Francesco B. Blasi, Marta F. Di Pasquale, Sofia Misuraca, Tommaso Pilocane, Edoardo Simonetta, Alessio M. Aghelmo, Claudio Angelini, Enrico Brunetta, Giorgio W. Canonica, Michele Ciccarelli, Sara Dal Farra, Maria De Santis, Sebastian Ferri, Marco Folci, Giacomo M. Guidelli, Enrico M. Heffler, Ferdinando Loiacono, Giacomo Malipiero, Giovanni Paoletti, Rosa Pedale, Francesca A. Puggioni, Francesca Racca, Aurora Zumbo, Morihiko Satou, Tatyana Lisun, Denis Protsenko, Nikolay Rubtsov, Irina Beloglazova, Daria Fomina, Mariana Lysenko, Sofia Serdotetskova, Vitali Firstov, Ivan Gordeev, Ilia Kokorin, Ksenia Komissarova, Nina Lapochkina, Elena Luchinkina, Valentin Malimon, Sevinch Mamedguseyinova, Ksenia Polubatonova, Natalia Suvorova, Jose Arribas, Alberto M. Borobia Perez, Fernando de la Calle Prieto, Juan Carlos Figueira, Rocio Motejano Sanchez, Marta Mora-Rillo, Concepcion Prados Sanchez, Javier Queiruga Parada, Francisco Fernandez Arnalich, Maria Guerro Barrientos, Alejandro Bendala Estrada, Aranzazu Caballero Marcos, Maria E. Garcia Leoni, Rita García-Martínez, Ana María Collado, Patricia Munoz Garcia, Ana Torres do Rego, María V. Villalba García, Almudena Burrillo, Maricela Valerio Minero, Paloma Gijon Vidaurreta, Sonsoles Infante Herrero, Elena Velilla, Marina Machado, Maria Olmedo, Blanca Pinilla, Benito Almirante Gragera, Maria de la Esperanza Cañas Ruano, Sofia Contreras Medina, Alejandro Cortés Herrera, Vicenç Falcó Ferrer, Ricard Ferrer Roca, Xavier Nuvials Casals, Esteve Ribera Pascuet, Paula Suanzes Diez, Pedro Rebollo Castro, Felipe Garcia Alcaide, Alejandro Soriano, Aina Oliver Caldes, Ana González Cordón, Celia Cardozo, Lorena De la Mora Cañizo, Romina Pena López, Sandra Chamorro, Clara Crespillo-Andujar, Rosa Escudero Sanchez, Jesús Fortún-Abete, Begoña Monge-Maillo, Ana Moreno Zamora, Francesca Norman, Matilde Sanchez Conde, Sergio Serrano Villar, Pilar Vizcarra, Lescure, F. -X., Honda, H., Fowler, R. A., Lazar, J. S., Shi, G., Wung, P., Patel, N., Hagino, O., Bazzalo, I. J., Casas, M. M., Nunez, S. A., Pere, Y., Ibarrola, C. M., Solis Aramayo, M. A., Cuesta, M. C., Duarte, A. E., Gutierrez Fernandez, P. M., Iannantuono, M. A., Miyazaki, E. A., Silvio, J. P., Scublinsky, D. G., Bales, A., Catarino, D., Fiss, E., Mohrbacher, S., Sato, V., Baylao, A., Cavalcante, A., Correa, F., de Andrade, C. A., Furtado, J., Ribeiro Filho, N., Telles, V., Trevelin, L. T., Vipich, R., Boldo, R., Borges, P., Lobo, S., Luckemeyer, G., Machado, L., Alves, M. B., Iglessias, A. C., Lago, M. M., Santos, D. W., Chapdelaine, H., Falcone, E. L., Jamal, R., Luong, M. -L., Durand, M., Doucet, S., Carrier, F. -M., Coburn, B. A., Del Sorbo, L., Walmsley, S. L., Belga, S., Chen, L. Y., Mah, A. D., Steiner, T., Wright, A. J., Hajek, J., Adhikari, N., Daneman, N., Khwaja, K. A., Shahin, J., Gonzalez, C., Silva, R., Lindh, M., Maluenda, G., Fernandez, P., Oyonarte, M., Lasso, M., Boyer, A., Bronnimann, D., Bui, H. -N., Cazanave, C., Chaussade, H., Desclaux, A., Ducours, M., Duvignaud, A., Malvy, D., Martin, L., Neau, D., Nguyen, D., Pistone, T., Soubrane-Wirth, G., Leitao, J., Allavena, C., Biron, C., Bouchez, S., Gaborit, B., Gregoire, A., Le Turnier, P., Lecompte, A. -S., Lecomte, R., Lefebvre, M., Raffi, F., Boutoille, D., Morineau, P. H., Guery, R., Chatelus, E., Dumoussaud, N., Felten, R., Luca, F., Goichot, B., Schneider, F., Taquet, M. -C., Groh, M., Roumier, M., Neuville, M., Bachelard, A., Isernia, V., Phung, B. -C., Rachline, A., Sautereau, A., Vallois, D., Bleher, Y., Boucher, D., Coudon, C., Esnault, J., Guimard, T., Leautez-Nainville, S., Merrien, D., Morrier, M., Motte-Vincent, P., Gabeff, R., Leclerc, H., Cozic, C., Decours, R., Fevrier, R., Colin, G., Abgrall, S., Vignes, D., Sterpu, R., Kuellmar, M., Meersch-Dini, M., Weiss, R., Zarbock, A., Antony, C., Berger, M., Brenner, T., Taube, C., Herbstreit, F., Dolff, S., Konik, M., Schmidt, K., Zettler, M., Witzke, O., Boell, B., Garcia Borrega, J., Koehler, P., Zander, T., Dusse, F., Al-Sawaf, O., Kohler, P., Eichenauer, D., Kochanek, M., Shimabukuro-Vornhagen, A., Mellinghoff, S., Classen, A., Heger, J. -M., Meyer-Schwickerath, C., Liedgens, P., Heindel, K., Belkin, A., Biber, A., Gilboa, M., Levy, I., Litachevsky, V., Rahav, G., Finesod Wiedner, A., Zilberman-Daniels, T., Oster, Y., Strahilevitz, J., Sviri, S., Baldissera, E. M., Campochiaro, C., Cavalli, G., Dagna, L., De Luca, Giacomo., Della Torre, E., Tomelleri, A., Bernasconi De Luca, D., Capetti, A. F., Coen, M., Cossu, M. V., Galli, M., Giacomelli, A., Gubertini, G. A., Rusconi, S., Burastero, G. J., Digaetano, M., Guaraldi, G., Meschiari, M., Mussini, C., Puzzolante, C., Volpi, S., Aiello, M., Ariani, A., Chetta, A. A., Frizzelli, A., Ticinesi, A., Tuttolomondo, D., Aliberti, S., Blasi, F. B., Di Pasquale, M. F., Misuraca, S., Pilocane, T., Simonetta, E., Aghelmo, A. M., Angelini, C., Brunetta, E., Canonica, G. W., Ciccarelli, M., Dal Farra, S., De Santis, M., Ferri, S., Folci, M., Guidelli, G. M., Heffler, E. M., Loiacono, F., Malipiero, G., Paoletti, G., Pedale, R., Puggioni, F. A., Racca, F., Zumbo, A., Satou, M., Lisun, T., Protsenko, D., Rubtsov, N., Beloglazova, I., Fomina, D., Lysenko, M., Serdotetskova, S., Firstov, V., Gordeev, I., Kokorin, I., Komissarova, K., Lapochkina, N., Luchinkina, E., Malimon, V., Mamedguseyinova, S., Polubatonova, K., Suvorova, N., Arribas, J., Borobia Perez, A. M., de la Calle Prieto, F., Figueira, J. C., Motejano Sanchez, R., Mora-Rillo, M., Prados Sanchez, C., Queiruga Parada, J., Fernandez Arnalich, F., Guerro Barrientos, M., Bendala Estrada, A., Caballero Marcos, A., Garcia Leoni, M. E., Garcia-Martinez, R., Collado, A. M., Munoz Garcia, P., Torres do Rego, A., Villalba Garcia, M. V., Burrillo, A., Valerio Minero, M., Gijon Vidaurreta, P., Infante Herrero, S., Velilla, E., Machado, M., Olmedo, M., Pinilla, B., Almirante Gragera, B., Canas Ruano, M. D. L. E., Contreras Medina, S., Cortes Herrera, A., Falco Ferrer, V., Ferrer Roca, R., Nuvials Casals, X., Ribera Pascuet, E., Suanzes Diez, P., Rebollo Castro, P., Garcia Alcaide, F., Soriano, A., Oliver Caldes, A., Gonzalez Cordon, A., Cardozo, C., De la Mora Canizo, L., Pena Lopez, R., Chamorro, S., Crespillo-Andujar, C., Escudero Sanchez, R., Fortun-Abete, J., Monge-Maillo, B., Moreno Zamora, A., Norman, F., Sanchez Conde, M., Serrano Villar, S., and Vizcarra, P.
Subjects: Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Critical Care, International Cooperation, Population, Antibodies, Monoclonal, Humanized, Placebo, Severity of Illness Index, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Intensive care, Severity of illness, medicine, Clinical endpoint, Humans, Immunologic Factors, 030212 general & internal medicine, Mortality, education, Respiratory Distress Syndrome, education.field_of_study, Dose-Response Relationship, Drug, SARS-CoV-2, business.industry, Hazard ratio, COVID-19, Articles, Middle Aged, Receptors, Interleukin-6, Sarilumab, Treatment Outcome, 030228 respiratory system, Female, Drug Monitoring, Cytokine Release Syndrome, business
Abstract: Summary Background Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group. Interpretation This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19. Funding Sanofi and Regeneron Pharmaceuticals.
Published: 2021

24. Severe acute respiratory syndrome coronavirus-2-induced flare of systemic sclerosis

Author: Marco Matucci-Cerinic, Nicola Farina, Corrado Campochiaro, Lorenzo Dagna, Anna Palmisano, G. De Luca, Davide Vignale, Campochiaro, C., De Luca, Giacomo., Farina, N., Vignale, D., Palmisano, A., Matucci-Cerinic, M., and Dagna, L.
Subjects: 2019-20 coronavirus outbreak, Scleroderma, Systemic, Coronavirus disease 2019 (COVID-19), SARS-CoV-2, business.industry, musculoskeletal, neural, and ocular physiology, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, Disease progression, COVID-19, macromolecular substances, General Medicine, nervous system, Rheumatology, Humans, Immunology and Allergy, Medicine, Respiratory system, business
Abstract: Systemic sclerosis (SSc) patients may develop severe coronavirus disease 2019 (COVID-19) (1), but no reports are available on disease progression following a severe acute respiratory syndrome coron...
Published: 2021

25. Drug retention rates of biological agents in adult onset Still's disease

Author: Lorenzo Dagna, Nicola Farina, Giacomo De Luca, Alessandro Tomelleri, Elena Baldissera, Giulio Cavalli, Corrado Campochiaro, Campochiaro, C., Farina, N., Tomelleri, A., De Luca, Giacomo., Baldissera, E., Cavalli, G., and Dagna, L.
Subjects: Adult, medicine.medical_specialty, 03 medical and health sciences, chemistry.chemical_compound, Biological Factors, 0302 clinical medicine, Tocilizumab, Rheumatology, Prednisone, Internal medicine, medicine, Humans, 030212 general & internal medicine, Retrospective Studies, 030203 arthritis & rheumatology, Anakinra, business.industry, Hazard ratio, Retrospective cohort study, Discontinuation, Anesthesiology and Pain Medicine, Treatment Outcome, chemistry, Pharmaceutical Preparations, Concomitant, Antirheumatic Agents, Cohort, business, Still's Disease, Adult-Onset, medicine.drug
Abstract: Objectives To assess drug retention rates (DRRs) and reasons for discontinuation of biologic disease-modifying antirheumatic drugs (bDMARDs) in a large monocentric cohort of patients with adult onset Still's disease (AOSD). Methods Clinical data of AOSD patients treated with at least one bDMARD and followed up at our Center were retrospectively evaluated. Data about disease duration, number of previous bDMARDs, concomitant treatments, and reasons for therapy discontinuation were collected. Survival curves were examined by the Kaplan-Meier method and compared using a stratified log-rank test. 24-month DRRs were calculated for each bDMARD. Hazard ratio (HR) for previous bDMARD use was evaluated. Results Forty-two AOSD patients received a total of 79 bDMARD-courses. Anakinra (ANK; n = 41) was the most frequently used bDMARD, followed by tocilizumab (TCZ; n = 21) and Tumor Necrosis Factor inhibitors (TNFi; n = 17). Biologic agents were administered concomitantly with prednisone in all cases (mean dose, 23 ± 18 mg/day) and with csDMARD therapy in 54 (68%) of courses. Thirty-six (46%) treatment courses were discontinued by 24 months. DRRs at 24 months were 62.5% for TCZ, 53.1% for ANK, and 11.8% for TNFi. ANK and TCZ DRRs were similar (p = 0.576), but significantly higher than TNFi (p = 0.015). Previous biologic therapies did not impact DRR (HR 0.73, 95% CI = 0.40 - 1.31, p = 0.288). Conclusions In our AOSD study population, 24 months DRRs of TCZ and ANK were similar and significantly higher than the TNFi DRR. Previous use of biologic agents did not affect DRRs.
Published: 2021

26. Oncogene-induced maladaptive activation of trained immunity in the pathogenesis and treatment of Erdheim-Chester disease

Author: Mihai G. Netea, Riccardo Biavasco, Lorenzo Dagna, Simone Cenci, Travis Nemkov, Giulio Cavalli, Philippe Maksud, Claudio Doglioni, Gianfranco Distefano, Daniela Cesana, Charles A. Dinarello, Eleonora Cantoni, Anna Kajaste-Rudnitski, Corrado Campochiaro, Simone Cardaci, Daniela Gnani, Isak W. Tengesdal, Julien Haroche, Samuel Zambrano, Alessandro Tomelleri, Giacomo De Luca, Davide Stefanoni, Francesco Piras, Ivan Merelli, Angelo D'Alessandro, Maddalena Panigada, Davide Mazza, Rob J.W. Arts, Jorge Domínguez-Andrés, Alessia Loffreda, Laura Cassina, Raffaella Molteni, Eugenio Montini, Alessandra Boletta, Leo A. B. Joosten, Elisabetta Ferrero, Marina Ferrarini, Biavasco, Riccardo, Molteni, Raffaella, Stefanoni, Davide, Nemkov, Travi, Netea, Mihai G., Domínguez-Andrés, Jorge, Arts, Rob JW, Merelli, Ivan, Mazza, Davide, Zambrano, S, Panigada, Maddalena, Cantoni, Eleonora, Tengesdal, Isak, Maksud, Philippe, Piras, Francesco, De Luca, Giacomo, Cassina, Laura, Distefano, Gianfranco, Loffreda, Alessia, Gnani, Daniela, Doglioni, Claudio, Tomelleri, Alessandro, Campochiaro, Corrado, Joosten, Leo, Dinarello, Charles A, Kajaste-Rudnitski, Anna, Haroche, Julien, Cardaci, Simone, Cenci, Simone, Dagna, Lorenzo, Ferrarini, Marina, Ferrero, Elisabetta, Boletta, Alessandra, D'Alessandro, Angelo, Montini, Eugenio, and Cavalli, Giulio
Subjects: Proto-Oncogene Proteins B-raf, Erdheim-Chester Disease, Myeloid, medicine.medical_treatment, Immunology, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Inflammation, Biochemistry, Myeloid Neoplasm, Proinflammatory cytokine, Epigenesis, Genetic, Pathogenesis, medicine, Humans, Point Mutation, Protein kinase B, Cells, Cultured, business.industry, Monocyte, Macrophages, Immunity, Cell Biology, Hematology, Oncogenes, Cytokine, medicine.anatomical_structure, Cancer research, medicine.symptom, business
Abstract: Trained immunity (TI) is a proinflammatory program induced in monocyte/macrophages upon sensing of specific pathogens and is characterized by immunometabolic and epigenetic changes that enhance cytokine production. Maladaptive activation of TI (ie, in the absence of infection) may result in detrimental inflammation and development of disease; however, the exact role and extent of inappropriate activation of TI in the pathogenesis of human diseases is undetermined. In this study, we uncovered the oncogene-induced, maladaptive induction of TI in the pathogenesis of a human inflammatory myeloid neoplasm (Erdheim-Chester disease, [ECD]), characterized by the BRAFV600E oncogenic mutation in monocyte/macrophages and excess cytokine production. Mechanistically, myeloid cells expressing BRAFV600E exhibit all molecular features of TI: activation of the AKT/mammalian target of rapamycin signaling axis; increased glycolysis, glutaminolysis, and cholesterol synthesis; epigenetic changes on promoters of genes encoding cytokines; and enhanced cytokine production leading to hyperinflammatory responses. In patients with ECD, effective therapeutic strategies combat this maladaptive TI phenotype; in addition, pharmacologic inhibition of immunometabolic changes underlying TI (ie, glycolysis) effectively dampens cytokine production by myeloid cells. This study revealed the deleterious potential of inappropriate activation of TI in the pathogenesis of human inflammatory myeloid neoplasms and the opportunity for inhibition of TI in conditions characterized by maladaptive myeloid-driven inflammation.
Published: 2021

27. The spectrum of covid-19-associated myocarditis: A patient-tailored multidisciplinary approach

Author: Paolo Della Bella, Silvia Sartorelli, Maria Grazia Calabrò, Paola Ferro, Andrea Villatore, Alberto Margonato, Francesco De Cobelli, Giovanni Peretto, Fabrizio Monaco, Paolo G. Camici, Cristina Basso, Lorenzo Dagna, Mara Scandroglio, Monica De Gaspari, Corrado Campochiaro, Antonio Esposito, Stefania Rizzo, Giulio Cavalli, Marco Ripa, Giacomo De Luca, Evgeny Fominskiy, Moreno Tresoldi, Patrizio Mazzone, Alberto Cappelletti, Simone Sala, Anna Palmisano, Elena Busnardo, Luigi Gianolli, Davide Vignale, Peretto, G., Villatore, A., Rizzo, S., Esposito, A., De Luca, Giacomo., Palmisano, A., Vignale, D., Cappelletti, A. M., Tresoldi, M., Campochiaro, C., Sartorelli, S., Ripa, M., De Gaspari, M., Busnardo, E., Ferro, P., Calabro, M. G., Fominskiy, E., Monaco, F., Cavalli, G., Gianolli, L., De Cobelli, F., Margonato, A., Dagna, L., Scandroglio, M., Camici, P. G., Mazzone, P., Della Bella, P., Basso, C., and Sala, S.
Subjects: medicine.medical_specialty, Myocarditis, Cardiac magnetic resonance, medicine.medical_treatment, Hemodynamics, Context (language use), 030204 cardiovascular system & hematology, Article, 03 medical and health sciences, 0302 clinical medicine, Ventricular arrhythmias, Internal medicine, Biopsy, medicine, 030212 general & internal medicine, Heart transplantation, Inflammation, Ejection fraction, Multidisciplinary, medicine.diagnostic_test, business.industry, SARS-CoV-2, COVID-19, Immunosuppression, General Medicine, medicine.disease, Cardiology, Etiology, Medicine, Endomyocardial biopsy, business
Abstract: Background. Myocarditis lacks systematic characterization in COVID-19 patients. Methods. We enrolled consecutive patients with newly diagnosed myocarditis in the context of COVID-19 infection. Diagnostic and treatment strategies were driven by a dedicated multidisciplinary disease unit for myocarditis. Multimodal outcomes were assessed during prospective follow-up. Results. Seven consecutive patients (57% males, age 51 ± 9 y) with acute COVID-19 infection received a de novo diagnosis of myocarditis. Endomyocardial biopsy was of choice in hemodynamically unstable patients (n = 4, mean left ventricular ejection fraction (LVEF) 25 ± 9%), whereas cardiac magnetic resonance constituted the first exam in stable patients (n = 3, mean LVEF 48 ± 10%). Polymerase chain reaction (PCR) analysis revealed an intra-myocardial SARS-CoV-2 genome in one of the six cases undergoing biopsy: in the remaining patients, myocarditis was either due to other viruses (n = 2) or virus-negative (n = 3). Hemodynamic support was needed for four unstable patients (57%), whereas a cardiac device implant was chosen in two of four cases showing ventricular arrhythmias. Medical treatment included immunosuppression (43%) and biological therapy (29%). By the 6-month median follow-up, no patient died or experienced malignant arrhythmias. However, two cases (29%) were screened for heart transplantation. Conclusions. Myocarditis associated with acute COVID-19 infection is a spectrum of clinical manifestations and underlying etiologies. A multidisciplinary approach is the cornerstone for tailored management.
Published: 2021

28. Covid-19 And Rheumatic Autoimmune Systemic Diseases: Role of Pre-Existing Lung Involvement and Ongoing Treatments

Author: M. L. Aprile, Rosario Foti, Ruscitti Piero, Giuseppe Varcasia, Ilaria Cavazzana, Nicoletta Romeo, Riccardo Meliconi, Serena Lorini, Serena Guiducci, Amelia Spinella, Roberto Giacomelli, Vincenzo Aiello, Alessandra Della Rossa, Giorgio Amato, Daiana Giannini, Vincenzo Raimondo, Francesco Caso, Ennio Lubrano, Silvia Bosello, Maurizio Caminiti, Monica Monti, Tasso Marco, Francesca Ingegnoli, Giorgio Pettiti, Massimo L'Andolina, Salvatore D'Angelo, Francesca Ragusa, Elisabetta Zanatta, Giacomo De Luca, Riccardo Cecchetti, Franco Franceschini, Greta Pellegrino, Silvia Bellando-Randone, Silvia Martina Ferrari, Micaela Fredi, Veronica Brusi, Lorenzo Dagna, Giusy Elia, Fabio Cacciapaglia, Francesco Ursini, Giuseppina Abignano, Sebastiano Lorusso, Clodoveo Ferri, Anna Linda Zignego, Rodolfo Caminiti, Sabrina Rosaria Paparo, Raffaele Brittelli, Liala Moschetti, Elena Generali, Marco Matucci-Cerinic, Roberta Pellegrini, Ylenia Dal Bosco, Giovanni Zanframundo, Domenico Olivo, Tommaso Ferrari, Alessandro Antonelli, M. Vadacca, Andrea Doria, Pietro Gigliotti, Poupak Varcasia, Enrico Fusaro, Elisa Visalli, Simone Barsotti, Giuseppa Pagano Mariano, Giovanna Cuomo, Florenzo Iannone, Maria De Santis, Valeria Mazzi, Giuseppe Murdaca, Michele Colaci, Silvia Bilia, Franco Cozzi, Dilia Giuggioli, Corrado Campochiaro, Valeria Riccieri, Erika Pigatto, Laura Gragnani, Ilenia Di Cola, Daniela Scorpiniti, Mario Miccoli, Francesco Masini, Veronica Codullo, Rossella De Angelis, Federica Lumetti, Antonio Tavoni, Ferri, Clodoveo, Giuggioli, Dilia, Raimondo, Vincenzo, L’Andolina, Massimo, Dagna, Lorenzo, Tavoni, Antonio, Caso, Francesco, Ursini, Francesco, Piero, Ruscitti, Caminiti, Maurizio, Foti, Rosario, Riccieri, Valeria, Guiducci, Serena, Pellegrini, Roberta, Zanatta, Elisabetta, Varcasia, Giuseppe, Olivo, Domenico, Gigliotti, Pietro, Cuomo, Giovanna, Murdaca, Giuseppe, Cecchetti, Riccardo, De Angelis, Rossella, Romeo, Nicoletta, Ingegnoli, Francesca, Cozzi, Franco, Codullo, Veronica, Cavazzana, Ilaria, Colaci, Michele, Abignano, Giuseppina, De Santis, Maria, Lubrano, Ennio, Fusaro, Enrico, Rossa, Alessandra Della, Spinella, Amelia, Lumetti, Federica, De Luca, Giacomo, Bellando-Randone, Silvia, Visalli, Elisa, Dal Bosco, Ylenia, Amato, Giorgio, Giannini, Daiana, Bilia, Silvia, Masini, Francesco, Pellegrino, Greta, Pigatto, Erika, Generali, Elena, Mariano, Giuseppa Pagano, Pettiti, Giorgio, Zanframundo, Giovanni, Brittelli, Raffaele, Aiello, Vincenzo, Caminiti, Rodolfo, Scorpiniti, Daniela, Ferrari, Tommaso, Campochiaro, Corrado, Brusi, Veronica, Fredi, Micaela, Moschetti, Liala, Cacciapaglia, Fabio, Gragnani, Laura, Monti, Monica, Lorini, Serena, Paparo, Sabrina Rosaria, Ragusa, Francesca, Mazzi, Valeria, Elia, Giusy, Ferrari, Silvia Martina, Di Cola, Ilenia, Vadacca, Marta, Lorusso, Sebastiano, Barsotti, Simone, Aprile, Maria Letizia, Marco, Tasso, Miccoli, Mario, Bosello, Silvia, Matucci-Cerinic, Marco, D'Angelo, Salvatore, Doria, Andrea, Franceschini, Franco, Meliconi, Riccardo, Iannone, Florenzo, Giacomelli, Roberto, Zignego, Anna Linda, Varcasia, Poupak, Antonelli, Alessandro, L'Andolina, Massimo, Della Rossa, Alessandra, Pagano Mariano, Giuseppa, Rosaria Paparo, Sabrina, Martina Ferrari, Silvia, Letizia Aprile, Maria, Linda Zignego, Anna, Ferri C., Giuggioli D., Raimondo V., L'andolina M., Dagna L., Tavoni A., Caso F., Ursini F., Ruscitti P., Caminiti M., Foti R., Riccieri V., Guiducci S., Pellegrini R., Zanatta E., Varcasia G., Olivo D., Gigliotti P., Cuomo G., Murdaca G., Cecchetti R., De Angelis R., Romeo N., Ingegnoli F., Cozzi F., Codullo V., Cavazzana I., Colaci M., Abignano G., De Santis M., Lubrano E., Fusaro E., Della Rossa A., Spinella A., Lumetti F., De Luca G., Bellando-Randone S., Visalli E., Dal Bosco Y., Amato G., Giannini D., Bilia S., Masini F., Pellegrino G., Pigatto E., Generali E., Mariano G.P., Pettiti G., Zanframundo G., Brittelli R., Aiello V., Caminiti R., Scorpiniti D., Ferrari T., Campochiaro C., Brusi V., Fredi M., Moschetti L., Cacciapaglia F., Gragnani L., Monti M., Lorini S., Paparo S.R., Ragusa F., Mazzi V., Elia G., Ferrari S.M., Di Cola I., Vadacca M., Lorusso S., Barsotti S., Aprile M.L., Marco T., Miccoli M., Bosello S., Matucci-Cerinic M., D'angelo S., Doria A., Franceschini F., Meliconi R., Iannone F., Giacomelli R., Zignego A.L., Fallahi P., and Antonelli A.
Subjects: medicine.medical_specialty, Settore MED/16 - REUMATOLOGIA, Referral, Coronavirus disease 2019 (COVID-19), autoimmune systemic disease, systemic sclerosis, Population, COVID-19, SARS-CoV-2, arthritis, autoimmune systemic diseases, connective tissue diseases, interstitial lung disease, rheumatic diseases, Arthritis, Keywords: COVID-19, Scleroderma, Autoimmune Diseases, Covid-19, Autoimmune systemic diseases, Connective tissue diseases, Interstitial lung disease, Rheumatic diseases, Systemic sclerosis, Internal medicine, Rheumatic Diseases, Drug Discovery, Pandemic, medicine, Humans, education, rheumatic disease, Lung, Pandemics, Pharmacology, education.field_of_study, Aspirin, business.industry, covid 19, medicine.disease, arthriti, connective tissue disease, business, medicine.drug
Abstract: Background: The Covid-19 pandemic may have a deleterious impact on patients with autoimmune systemic diseases (ASD) due to their deep immune-system alterations. Objective: This study aims to investigate the prevalence of symptomatic Covid-19 and its correlations with both organ involvement and ongoing treatments in a large series of Italian ASD patients during the first wave of pandemic. Methods: Our multicenter telephone 6-week survey included 3,029 unselected ASD patients enrolled at 36 tertiary referral centers of northern, central, and southern Italian macro-areas with different diffusion of the pandemic. Symptomatic SARS-CoV-2 infection was classified as definite Covid-19 (presence of symptoms plus positive oral/nasopharyngeal swabs) or highly suspected Covid-19 (highly suggestive symptoms, in the absence of a swab testing). Results: A significantly higher prevalence of definite plus highly suspected Covid-19 compared to the Italian general population was detected in the whole ASD series (p=.000), as well as in patients from the three macro-areas (p=.000 in all). Statistically higher prevalence of Covid-19 was also found in connective tissue diseases compared to chronic arthritis subgroup (p=.000) and in ASD patients with pre-existing interstitial lung involvement (p=.000). Patients treated with either conventional disease-modifying anti-rheumatic drugs (DMARDs) and/or biological DMARDs showed a significantly lower prevalence of Covid-19 (p=.000 in both). Finally, scleroderma patients undergoing low-dose aspirin showed a significantly lower rate of Covid-19 compared to those without (p=0.003). Conclusion: The higher prevalence of Covid-19 in ASD patients, along with the significant correlations with important clinical features and therapeutic regimens, suggests the need to develop targeted prevention/management strategies during the current pandemic wave.
Published: 2021

29. COVID-19 and systemic sclerosis: clinicopathological implications from Italian nationwide survey study

Author: Clodoveo Ferri, Dilia Giuggioli, Vincenzo Raimondo, Lorenzo Dagna, Valeria Riccieri, Elisabetta Zanatta, Serena Guiducci, Antonio Tavoni, Rosario Foti, Giovanna Cuomo, Rossella De Angelis, Franco Cozzi, Giuseppe Murdaca, Ilaria Cavazzana, Nicoletta Romeo, Veronica Codullo, Francesca Ingegnoli, Roberta Pellegrini, Giuseppe Varcasia, Alessandra Della Rossa, Maria De Santis, Giuseppina Abignano, Michele Colaci, Maurizio Caminiti, Massimo L'Andolina, Ennio Lubrano, Amelia Spinella, Federica Lumetti, Giacomo De Luca, Silvia Bellando-Randone, Elisa Visalli, Silvia Bilia, Daiana Giannini, Francesco Masini, Greta Pellegrino, Erika Pigatto, Elena Generali, Francesca Dall'Ara, Giuseppa Pagano Mariano, Simone Barsotti, Giorgio Pettiti, Giovanni Zanframundo, Raffaele Brittelli, Vincenzo Aiello, Daniela Scorpiniti, Tommaso Ferrari, Rodolfo Caminiti, Corrado Campochiaro, Salvatore D'Angelo, Florenzo Iannone, Marco Matucci-Cerinic, Andrea Doria, Mario Miccoli, Poupak Fallahi, Alessandro Antonelli, Riccardo Cecchetti, Pietro Gigliotti, Domenico Olivo, Francesco Ursini, Veronica Brusi, Riccardo Meliconi, Raffaele Scarpa, Enrico Fusaro, Anna Linda Zignego, Sabrina Rosaria Paparo, Francesca Ragusa, Giusy Elia, Silvia Martina Ferrari, Ferri, C., Giuggioli, D., Raimondo, V., Dagna, L., Riccieri, V., Zanatta, E., Guiducci, S., Tavoni, A., Foti, R., Cuomo, G., De Angelis, R., Cozzi, F., Murdaca, G., Cavazzana, I., Romeo, N., Codullo, V., Ingegnoli, F., Pellegrini, R., Varcasia, G., Rossa, A. D., De Santis, M., Abignano, G., Colaci, M., Caminiti, M., L'Andolina, M., Lubrano, E., Spinella, A., Lumetti, F., De Luca, G., Bellando-Randone, S., Visalli, E., Bilia, S., Giannini, D., Masini, F., Pellegrino, G., Pigatto, E., Generali, E., Dall'Ara, F., Mariano, G. P., Barsotti, S., Pettiti, G., Zanframundo, G., Brittelli, R., Aiello, V., Scorpiniti, D., Ferrari, T., Caminiti, R., Campochiaro, C., D'Angelo, S., Iannone, F., Matucci-Cerinic, M., Doria, A., Miccoli, M., Fallahi, P., Antonelli, A., Della Rossa, A., Pagano Mariano, G., Cecchetti, R., Gigliotti, P., Olivo, D., Ursini, F., Brusi, V., Meliconi, R., Scarpa, R., Fusaro, E., Zignego, A. L., Paparo, S. R., Ragusa, F., Elia, G., Ferrari, S. M., Ferri C., Giuggioli D., Raimondo V., Dagna L., Riccieri V., Zanatta E., Guiducci S., Tavoni A., Foti R., Cuomo G., De Angelis R., Cozzi F., Murdaca G., Cavazzana I., Romeo N., Codullo V., Ingegnoli F., Pellegrini R., Varcasia G., Rossa A.D., De Santis M., Abignano G., Colaci M., Caminiti M., L'Andolina M., Lubrano E., Spinella A., Lumetti F., De Luca G., Bellando-Randone S., Visalli E., Bilia S., Giannini D., Masini F., Pellegrino G., Pigatto E., Generali E., Dall'Ara F., Mariano G.P., Barsotti S., Pettiti G., Zanframundo G., Brittelli R., Aiello V., Scorpiniti D., Ferrari T., Caminiti R., Campochiaro C., D'Angelo S., Iannone F., Matucci-Cerinic M., Doria A., Miccoli M., Fallahi P., Antonelli A., Della Rossa A., Pagano Mariano G., Cecchetti R., Gigliotti P., Olivo D., Ursini F., Brusi V., Meliconi R., Scarpa R., Fusaro E., Zignego A.L., Paparo S.R., Ragusa F., Elia G., Ferrari S.M., and De Luca, Giacomo.
Subjects: medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, MEDLINE, COVID-19, Nationwide survey, Rheumatology, Family medicine, Systemic sclerosis, Immunology and Allergy, Medicine, business
Abstract: None
Published: 2021

30. Repurposing of Biologic and Targeted Synthetic Anti-Rheumatic Drugs in COVID-19 and Hyper-Inflammation: A Comprehensive Review of Available and Emerging Evidence at the Peak of the Pandemic

Author: Giulio Cavalli, Nicola Farina, Corrado Campochiaro, Giacomo De Luca, Emanuel Della-Torre, Alessandro Tomelleri, Lorenzo Dagna, Cavalli, G., Farina, N., Campochiaro, C., De Luca, Giacomo., Della-Torre, E., Tomelleri, A., and Dagna, L.
Subjects: 0301 basic medicine, medicine.medical_treatment, Inflammation, Review, Disease, DMARDs (biologic), disease modifying anti-rheumatic drug, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Tocilizumab, medicine, cytokine, Pharmacology (medical), 030203 arthritis & rheumatology, Pharmacology, Anakinra, Coronavirus disease 2019, JAK inhibitors, business.industry, lcsh:RM1-950, immunesuppressants, Sarilumab, lcsh:Therapeutics. Pharmacology, 030104 developmental biology, Cytokine, chemistry, Immunology, Tumor necrosis factor alpha, medicine.symptom, Janus kinase, business, medicine.drug, severe acute respiratory syndrome coronavirus 2
Abstract: Coronavirus disease 2019 (COVID-19) is a condition caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Severe cases of COVID-19 result in acute respiratory distress syndrome and death. A detrimental, hyper-inflammatory immune response with excess release of cytokines is the main driver of disease development and of tissue damage in these patients. Thus, repurposing of biologic agents and other pharmacological inhibitors of cytokines used for the treatment of various inflammatory conditions emerged as a logical therapeutic strategy to quench inflammation and improve the clinical outcome of COVID-19 patients. Evaluated agents include the interleukin one receptor blocker anakinra, monoclonal antibodies inhibiting IL-6 tocilizumab and sarilumab, monoclonal antibodies inhibiting granulocyte-monocyte colony stimulating factor and tumor necrosis factor, and Janus kinase inhibitors. In this review, we discuss the efficacy and safety of these therapeutic options based on direct personal experience and on published evidence from observational studies and randomized clinical trials.
Published: 2020

31. Safety and efficacy of rituximab biosimilar (CT-P10) in systemic sclerosis: an Italian multicentre study

Author: Corrado Campochiaro, Andrea Doria, Paolo Airò, S. L. Bosello, Maria De Santis, Maria Grazia Lazzaroni, Cosimo Bruni, Carlo Selmi, Lorenzo Dagna, Elisa Gremese, Adriana Cariddi, Marco Matucci-Cerinic, Elisabetta Zanatta, Giacomo De Luca, Campochiaro, Corrado, DE LUCA, Giacomo, Grazia Lazzaroni, Maria, Zanatta, Elisabetta, Laura Bosello, Silvia, De Santis, Maria, Cariddi, Adriana, Bruni, Cosimo, Selmi, Carlo, Gremese, Elisa, Matucci-Cerinic, Marco, Doria, Andrea, Airò, Paolo, and Dagna, Lorenzo
Subjects: Adult, Male, medicine.medical_specialty, skin, systemic sclerosis, bDMARD, Arthritis, Neutropenia, Systemic scleroderma, Gastroenterology, Pulmonary function testing, B cell, CD20, biologic, biosimilar, interstitial lung disease, rituximab, scleroderma, 03 medical and health sciences, Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, Rheumatology, Internal medicine, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Aged, Retrospective Studies, 030203 arthritis & rheumatology, Scleroderma, Systemic, business.industry, Interstitial lung disease, Retrospective cohort study, Middle Aged, medicine.disease, Treatment Outcome, Concomitant, Antirheumatic Agents, Rituximab, Female, business, medicine.drug
Abstract: Objectives Recent data have shown a significant efficacy of rituximab (RTX) in SSc. An RTX biosimilar (RTX-B) is a more affordable option. We assessed the safety and efficacy of an RTX-B (CT-P10) in SSc. Methods SSc patients treated with RTX-B with at least 6 months of follow-up were retrospectively identified from six Italian referral centres. SSc patients naïve to RTX-B (RTX-Bn) or already treated with RTX originator and switched to an RTX-B (RTX-Bs) were evaluated. A comprehensive assessment of disease characteristics and organ involvement at baseline and after 6 months was obtained. Results Thirty-three SSc patients were selected: 29 (87.9%) females, mean age 51.6 years (s.d. 14.2), mean disease duration 9.8 years (s.d. 8.1); 21 (64.5%) with dcSSc, 20 (60.1%) anti-topoisomerase I, 7 (21.2%) anti-RNA polymerase III and 6 (18.2%) anti-centromere positive. Seventeen (51.5%) were RTX-Bn and 16 were on RTX-Bs (48.5%). RTX was introduced because of skin progression in 18 patients (54.5%), interstitial lung disease (ILD) worsening in 11 (33.3%) and arthritis in 12 (36.4%). All patients were previously treated with immunosuppressants. At RTX-B introduction, 21 (63.6%) patients were on concomitant immunosuppressants: 15 (71.4%) on MMF and 6 (28.6%) on MTX. Twenty-three (69.7%) were on low-dose steroids. After 6 months, a significant reduction of the modified Rodnan skin score (mRSS), 28-joint DAS and CRP was observed (P = 0.002, 0.005 and 0.008, respectively); the mRSS significantly improved both in RTX-Bn (P Conclusion Our data suggest that RTX-B can represent a cheaper option in SSc patients, as it is effective in improving skin and joint involvement and in stabilizing lung function.
Published: 2019

32. Large-vessel Vasculitis Affecting the Aorta and its Branches in Relapsing Polychondritis: Case Series and Systematic Review of the Literature

Author: Corrado Campochiaro, Silvia Sartorelli, Lorenzo Dagna, Alessandro Tomelleri, Elena Baldissera, Giulio Cavalli, Giacomo De Luca, Maurizio Papa, Tomelleri, Alessandro, Campochiaro, Corrado, Sartorelli, Silvia, Papa, Maurizio, De Luca, Giacomo, Cavalli, Giulio, Baldissera, Elena, and Dagna, Lorenzo
Subjects: Aorta, medicine.medical_specialty, business.industry, Immunology, Giant Cell Arteritis, MEDLINE, medicine.disease, Dermatology, Systematic review, Rheumatology, medicine.artery, Large vessel vasculitis, Antirheumatic Agents, medicine, Immunology and Allergy, Humans, In patient, Arteritis, Polychondritis, Relapsing, Vasculitis, business, Relapsing polychondritis, Retrospective Studies
Abstract: ObjectiveTo describe the features of large-vessel vasculitis (LVV) as it affects the aorta and its branches in patients with relapsing polychondritis (RP).MethodsRetrospective data and systematic literature review.ResultsTwenty-one patients were identified. LVV diagnosis was subsequent to RP and associated with extrachondral involvement in the majority of patients. Supraaortic vessels were more frequently involved (82%). Fourteen patients (67%) were treated with a conventional synthetic disease-modifying antirheumatic drug (csDMARD) and 7 (33%) with a biological DMARD (bDMARD). Vascular interventional procedures were performed in 10 patients (48%). Premature death due to cardiovascular complications was reported in 3 cases (14%).ConclusionExtraaortic LVV is a serious and overlooked RP manifestation. All patients with RP should be investigated for LVV.
Published: 2019

33. A Novel Histiocytosis With Synovial and Skin Involvement

Author: Elisabetta Ferrero, Giulio Cavalli, Claudio Doglioni, Lorenzo Dagna, Marina Ferrarini, Giacomo De Luca, Cavalli, Giulio, De Luca, Giacomo, Doglioni, Claudio, Ferrero, Elisabetta, Ferrarini, Marina, and Dagna, Lorenzo
Subjects: medicine.medical_specialty, Histiocytosis, Text mining, business.industry, Internal Medicine, medicine, MEDLINE, General Medicine, business, medicine.disease, Dermatology
Published: 2021

34. Mavrilimumab for severe COVID-19 – Authors' reply

Author: Giulio Cavalli, Corrado Campochiaro, Lorenzo Dagna, Giacomo De Luca, Emanuel Della-Torre, De Luca, Giacomo., Cavalli, G., Campochiaro, C., Della-Torre, E., and Dagna, L.
Subjects: 2019-20 coronavirus outbreak, Rheumatology, Coronavirus disease 2019 (COVID-19), Mavrilimumab, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Correspondence, Immunology, Immunology and Allergy, Medicine, business, Virology
Published: 2020

35. Tocilizumab for the Treatment of Myocardial Inflammation Shown by Cardiac Magnetic Resonance: Report of Two Cases and Rationale for Its Therapeutic Use

Author: Alessandro Tomelleri, Silvia Sartorelli, Giulio Cavalli, Lorenzo Dagna, Simone Sala, Giovanni Peretto, Anna Palmisano, Corrado Campochiaro, Antonio Esposito, Giacomo De Luca, Campochiaro, Corrado, De Luca, Giacomo, Tomelleri, Alessandro, Sartorelli, Silvia, Peretto, Giovanni, Sala, Simone, Palmisano, Anna, Esposito, Antonio, Cavalli, Giulio, and Dagna, Lorenzo
Subjects: Inflammation, medicine.medical_specialty, Magnetic Resonance Spectroscopy, business.industry, Myocardial inflammation, MEDLINE, Antibodies, Monoclonal, Humanized, Magnetic Resonance Imaging, chemistry.chemical_compound, Myocarditis, Text mining, Tocilizumab, Rheumatology, chemistry, Internal medicine, Cardiology, Medicine, Humans, business, Cardiac magnetic resonance
Published: 2019

36. Diagnostic approach and novel therapeutic option for cardiac inflammatory disorders. Comment on 'Antisynthetase syndrome and cardiac involvement: a rare association' by Meudec et al. Joint Bone Spine 2018. doi: 10.1016/j.jbspin.2018.09.019

Author: Silvia Sartorelli, Corrado Campochiaro, Giacomo De Luca, Sartorelli, S., Campochiaro, C., and De Luca, Giacomo.
Subjects: medicine.medical_specialty, Anakinra, Myocarditis, business.industry, Interleukin, Joint bone, Antisynthetase syndrome, medicine.disease, Dermatology, Rheumatology, medicine, business, medicine.drug, Interleukin-1
Published: 2019

37. Efficacy and Safety of Methotrexate for the Treatment of Autoimmune Virus-Negative Myocarditis: A Case Series

Author: C. Candela, Giacomo De Luca, Silvia Sartorelli, Giulio Cavalli, Lorenzo Dagna, Alessandro Tomelleri, Corrado Campochiaro, Antonio Esposito, Campochiaro, Corrado, De Luca, Giacomo, Sartorelli, Silvia, Tomelleri, Alessandro, Esposito, Antonio, Candela, Caterina, Cavalli, Giulio, and Dagna, Lorenzo
Subjects: 030203 arthritis & rheumatology, Myocarditis, business.industry, Myocardium, MEDLINE, 030204 cardiovascular system & hematology, medicine.disease, Virus, Autoimmune Diseases, 03 medical and health sciences, 0302 clinical medicine, Methotrexate, Rheumatology, Immunology, medicine, Humans, business, medicine.drug
Published: 2018

38. The fibrogenic chemokine CCL18 is associated with disease severity in Erdheim-Chester disease

Author: Guido Pacini, Greta Pacini, Alessandro Tomelleri, Lorenzo Dagna, Giacomo De Luca, Giulio Cavalli, Marina Ferrarini, Claudio Doglioni, Pacini, Greta, Cavalli, Giulio, Tomelleri, Alessandro, De Luca, Giacomo, Pacini, Guido, Ferrarini, Marina, Doglioni, Claudio, and Dagna, Lorenzo
Subjects: 0301 basic medicine, lcsh:Immunologic diseases. Allergy, Chemokine, Pathology, medicine.medical_specialty, genetic structures, Immunology, Disease, lcsh:RC254-282, CCL-18, Pathogenesis, 03 medical and health sciences, Disease severity, Fibrosis, Immunology and Allergy, Medicine, erdheim-chester disease, biology, business.industry, Brief Report, fibrosis, CCL18, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Histiocytosis, 030104 developmental biology, Oncology, Erdheim–Chester disease, biology.protein, Erdheim-Chester disease, ccl-18, business, lcsh:RC581-607
Abstract: Erdheim-Chester disease (ECD) is a rare histiocytosis, characterized by xanthogranulomatous tissue infiltration by foamy histiocytes. Fibrosis, a histologic hallmark of ECD, is responsible for lesion growth and clinical manifestations. Unraveling molecular fibrotic pathway in ECD would allow the identification of new pharmacologic targets. In this study, we evaluated serum and tissue samples from a large cohort of ECD patients focusing on two major pro-fibrotic mediators, TGF-β1 and chemokine ligand 18 (CCL18). We found a marked increase in CCL18 but not TGF-β1 levels in serum and lesions of ECD patients (p < 0.001), independently of treatment status and consistently over time. Using a linear mathematical model, we also found that elevated CCL18 serum levels correlate with both number and severity of disease localizations. These findings suggest the involvement of CCL18-induced fibrosis in ECD pathogenesis, providing a rationale for exploring CCL18 inhibition as a treatment for progressive fibrosis in ECD.
Published: 2018

39. Treating Heart Inflammation With Interleukin-1 Blockade in a Case of Erdheim–Chester Disease

Author: Alessandro Tomelleri, Teresa D'Aliberti, Giacomo De Luca, Corrado Campochiaro, Moreno Tresoldi, Lorenzo Dagna, Giulio Cavalli, Tomelleri, Alessandro, Cavalli, Giulio, De Luca, Giacomo, Campochiaro, Corrado, D'Aliberti, Teresa, Tresoldi, Moreno, and Dagna, Lorenzo
Subjects: lcsh:Immunologic diseases. Allergy, Male, 0301 basic medicine, Erdheim-Chester Disease, medicine.medical_specialty, Heart disease, Erdheim–Chester disease, Immunology, pericarditis, Pericardial effusion, Gastroenterology, Pericardial Effusion, 03 medical and health sciences, Pericarditis, 0302 clinical medicine, Internal medicine, Cardiac tamponade, cytokine, medicine, Humans, Immunology and Allergy, Pericardium, Radionuclide Imaging, 030203 arthritis & rheumatology, Anakinra, business.industry, Receptors, Interleukin-1, Middle Aged, medicine.disease, cytokines, Interleukin 1 Receptor Antagonist Protein, Myocarditis, Treatment Outcome, 030104 developmental biology, medicine.anatomical_structure, inflammation, Echocardiography, Heart failure, lcsh:RC581-607, Tomography, X-Ray Computed, business, interleukin-1, anakinra, Interleukin-1, medicine.drug
Abstract: Pericarditis is an inflammatory heart disease, which may be idiopathic or secondary to autoimmune or auto-inflammatory diseases and often leads to severe or life-threatening complications. Colchicine and non-steroidal anti-inflammatory drugs represent the mainstay of treatment, whereas use of corticosteroids is associated with recurrence of disease flares. While effective and safe anti-inflammatory therapies remain an unmet clinical need, emerging clinical and experimental evidence points at a promising role of inhibition of the pro-inflammatory cytokine interleukin-1 (IL-1). We thus evaluated treatment with the IL-1 receptor antagonist anakinra in a case of extremely severe pericarditis with cardiac tamponade and heart failure secondary to Erdheim-Chester disease (ECD), a rare clonal disorder of macrophages characterized by rampant inflammation and multiorgan involvement. A 62-year-old man was admitted to the Emergency Department with severe pericardial effusion requiring the creation of a pleuro-pericardial window. A whole-body contrast-enhanced computed tomography pointed at a diagnosis of ECD with involvement of the heart and pericardium and of the retroperitoneal space. Over the following days, an echocardiography revealed a closure of the pleuro-pericardial window and a relapse of the pericardial effusion. Treatment with anakinra, the recombinant form of the naturally occurring IL-1 receptor antagonist, was started at a standard subcutaneous dose of 100 mg/day. After 2 days, we observed a dramatic clinical improvement, an abrupt reduction of the inflammatory markers, and a reabsorption of the pericardial effusion. Anakinra was maintained as monotherapy, and the patient remained asymptomatic in the absence of disease flares for the following year. Recent studies point at inhibition of IL-1 activity as an attractive treatment option for patients with refractory idiopathic recurrent pericarditis. Anakinra treatment may also have a role in patients with pericarditis in the setting of systemic inflammatory disorders, such as ECD.
Published: 2018

40. Abnormal Cardiac Biomarkers in Patients with Systemic Lupus Erythematosus and No Prior Heart Disease: The Role of Endomyocardial Biopsy

Author: Corrado Campochiaro, Lorenzo Dagna, Giacomo De Luca, de Luca, Giacomo, Campochiaro, Corrado, and Dagna, Lorenzo
Subjects: medicine.medical_specialty, Allergy, Heart Diseases, Heart disease, Biopsy, Immunology, Disease, Antimalarials, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Internal medicine, medicine, Humans, Lupus Erythematosus, Systemic, Immunology and Allergy, 030212 general & internal medicine, 030203 arthritis & rheumatology, biology, business.industry, medicine.disease, Brain natriuretic peptide, Cohort, biology.protein, Cardiology, Biomarker (medicine), Creatine kinase, business, Biomarkers
Abstract: To the Editor: Tselios, et al reported in their recent study that patients with systemic lupus erythematosus (SLE) who receive prolonged antimalarial (AM) treatment are at increased risk for elevated cardiac biomarkers [brain natriuretic peptide (BNP) and high-sensitivity cardiac troponin I (HS-cTnI)], particularly when persistently elevated creatine phosphokinase (CPK) is present1. Among a well-characterized SLE cohort of 179 patients, the authors found that 16 (all without cardiac disease, renal failure, or pulmonary arterial hypertension) presented an increase of at least 1 cardiac biomarker. Prolonged AM use (> 5.6 yrs) was found to be associated with these laboratory abnormalities, regardless of age and SLE disease duration1. Regarding the potential reason underlying these findings, the authors speculated that AM deposition in muscle tissue (expressed with chronic CPK elevation) could not be restricted to skeletal muscles, and the drug could also accumulate within the myocardium. Therefore, they proposed the evaluation of these cardiac biomarkers as a screening tool for patients with SLE receiving AM … Address correspondence to Dr. G. De Luca, Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina 60, 20132, Milan, Italy. E-mail: deluca.giacomo{at}hsr.it
Published: 2019

41. Advances in potential targeted therapies for Erdheim-Chester disease

Author: Giulio Cavalli, Lorenzo Dagna, Giacomo De Luca, Cavalli, Giulio, De Luca, Giacomo, and Dagna, Lorenzo
Subjects: 0301 basic medicine, Neuroblastoma RAS viral oncogene homolog, genetic structures, myeloid neoplasm, Disease, Myeloid Neoplasm, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Medicine, Langerhansâ cell histiocytosi, Pharmacology (medical), dabrafenib, Vemurafenib, cobimetinib, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Trametinib, trametinib, business.industry, Health Policy, oncogene-induced senescence, medicine.disease, Histiocytosis, 030104 developmental biology, Anakinra, 030220 oncology & carcinogenesis, Erdheim–Chester disease, Cancer research, vemurafenib, business, medicine.drug
Abstract: Introduction: Erdheim-Chester disease (ECD) is a rare histiocytosis, characterized by infiltration of aberrant macrophages into multiple tissues and organs causing rampant inflammation and fibrosis. The clinical severity and the nuances of disease pathogenesis must be considered when pondering different treatment strategies for the individual patient. Areas covered: Interferon-Î± has long represented the first-line treatment for ECD, but its preeminence may be reappraised in the future as new effective medications become available. For example, alternative treatment options include cytokine-blocking agents, which dampen local and systemic inflammation. Of crucial importance, recent evidence indicates that deregulated activation of the mitogen-activated protein kinase (MAPK) pathway due to oncogenic mutations in the BRAF, NRAS, PIK3CA, and MAP2K1 genes is central to the pathogenesis of ECD. These advances in the molecular understanding of ECD as an inflammatory myeloid neoplasm translated into the therapeutic use of small-molecule RAF and MEK inhibitors, with unprecedented results in terms of clinical efficacy. Expert opinion: In the future, the development of ERK inhibitors holds tremendous promise for the treatment of ECD. Combination therapy with small-molecule plus anti-inflammatory agents may prove more beneficial than either treatment alone. New drugs against fibrosis, not amenable to treatment with currently available strategies, remain an unmet clinical need.
Published: 2017

42. Adult leukoencephalopathies with prominent infratentorial involvement can be caused by Erdheim-Chester disease

Author: Luisa Chiapparini, Lorenzo Dagna, Davide Pareyson, Anna Venerando, Sergio Raspante, Tiziana Langella, Giulio Cavalli, Andrea Botturi, Simonetta Gerevini, Maria Giulia Cangi, Ettore Salsano, Giacomo De Luca, Giorgio Marotta, Giuseppe Lauria, Bianca Pollo, Chiapparini, Luisa, Cavalli, Giulio, Langella, Tiziana, Venerando, Anna, de Luca, Giacomo, Raspante, Sergio, Marotta, Giorgio, Pollo, Bianca, Lauria, Giuseppe, Cangi, Maria Giulia, Gerevini, Simonetta, Botturi, Andrea, Pareyson, Davide, Dagna, Lorenzo, and Salsano, Ettore
Subjects: Adult, Brain Infarction, Male, medicine.medical_specialty, Pathology, Erdheim-Chester Disease, Neurology, Indoles, Antineoplastic Agents, ErdheimâChester disease, Imaging, Leukoencephalopathy, White matter, 03 medical and health sciences, 0302 clinical medicine, Leukoencephalopathies, White matter lesion, Cerebellum, medicine, Humans, Longitudinal Studies, Sulfonamides, Cerebellar ataxia, medicine.diagnostic_test, business.industry, Leukodystrophy, Middle Aged, medicine.disease, Histiocytosi, Magnetic Resonance Imaging, Histiocytosis, medicine.anatomical_structure, Bone scintigraphy, Vemurafenib, 030220 oncology & carcinogenesis, Erdheim–Chester disease, Female, Neurology (clinical), medicine.symptom, business, Tomography, X-Ray Computed, 030217 neurology & neurosurgery, Brain Stem
Abstract: Background: Leukoencephalopathies with prominent involvement of cerebellum and brainstem, henceforward called prominent infratentorial leukoencephalopathies (PILs), encompass a variety of inherited and acquired white matter diseases. ErdheimâChester disease (ECD) is a rare non-Langerhans cell histiocytosis likely under-diagnosed as cause of adult PIL. Methods: We reviewed the clinical and laboratory information of ten consecutive sporadic adult patients with PIL of unknown origin, who were investigated for ECD. Results: There were seven males and three females; mean age at clinical onset was 49.6 years (range 38â59); cerebellar ataxia with or without other neurological symptoms was the only or the main clinical manifestation; diabetes insipidus was present in three individuals. Eight patients had white matter focal supratentorial abnormalities, in addition to the infratentorial white matter changes. Six out of eight patients had spinal cord lesions. Thoraco-abdominal CT showed periaortic sheathing in two patients, whole-body FDG-PET revealed increased glucose uptake in the long bones of the legs in five patients, brain FDG-PET showed overt infratentorial hypermetabolism in one patient. In eight patients, ECD was confirmed by bone scintigraphy, pathological data, or both. Two ECD patients treated with vemurafenib showed a marked improvement of neurological symptoms and brain MRI abnormalities at 1 year follow-up. Conclusions: Symptoms of PIL can be the only clinical manifestation of ECD. Adult patients with PIL of unknown origin should undergo investigations aimed at unveiling ECD, including bone scintigraphy and whole-body FDG-PET. The early diagnosis allows starting disease-modifying therapies of an otherwise life-threatening disease.
Published: 2017

43. QTc interval prolongation in Systemic Sclerosis: Correlations with clinical variables and arrhythmic risk

Author: G. Canestrari, Lorenzo Dagna, Gianfranco Ferraccioli, Giulio Cavalli, Silvia Laura Bosello, Giacomo De Luca, De Luca, Giacomo, Bosello, Silvia Laura, Canestrari, Giovanni, Cavalli, Giulio, Dagna, Lorenzo, and Ferraccioli, Gianfranco
Subjects: Risk, 030203 arthritis & rheumatology, medicine.medical_specialty, Scleroderma, Systemic, Clinical variables, Settore MED/16 - REUMATOLOGIA, Arrhythmic risk, business.industry, systemic sclerosis, Medicine (all), Arrhythmias, Cardiac, 030204 cardiovascular system & hematology, Electrocardiography, Long QT Syndrome, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Cardiology, medicine, Qtc interval prolongation, Humans, Cardiology and Cardiovascular Medicine, business
Published: 2017

44. Anti-PD1 therapy-associated cutaneous leucocytoclastic vasculitis: A case series

Author: Corrado Campochiaro, Lorenzo Dagna, Giulio Cavalli, Giacomo De Luca, Alessandro Tomelleri, Tomelleri, Alessandro, Campochiaro, Corrado, De Luca, Giacomo, Cavalli, Giulio, and Dagna, Lorenzo
Subjects: Vasculitis, 030203 arthritis & rheumatology, Leucocytoclastic vasculitis, medicine.medical_specialty, business.industry, Immune checkpoint inhibitors, Leucocytoclastic vasculiti, Immune checkpoint inhibitor, medicine.disease, Dermatology, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal Medicine, medicine, Lung cancer, Anti pd1, business
Published: 2018

45. Anti-Ku syndrome with elevated CK: association with myocardial involvement in systemic sclerosis

Author: Maria De Santis, Corrado Campochiaro, Giacomo De Luca, Campochiaro, C., De Luca, Giacomo., and De Santis, M.
Subjects: 0301 basic medicine, medicine.medical_specialty, Myocarditis, autoantibodies, systemic sclerosis, Immunology, Polymyositis, General Biochemistry, Genetics and Molecular Biology, polymyositis, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Internal medicine, medicine, Humans, Immunology and Allergy, skin and connective tissue diseases, 030203 arthritis & rheumatology, Scleroderma, Systemic, business.industry, Interstitial lung disease, Autoantibody, medicine.disease, Connective tissue disease, 030104 developmental biology, Cohort, business, Rheumatism
Abstract: We read with great interest the paper by Spielmann et al describing a large cohort of anti-Ku-positive connective tissue disease patients.1 In their paper, the authors could identify two different subgroups of patients: ‘anti-Ku with elevated CK patients’, who are at risk of developing interstitial lung disease (ILD), and ‘anti-Ku with anti-dsDNA patients’, who are at risk of developing glomerulonephritis. Interestingly, the authors found an extremely low rate of myocarditis in both subgroups as only one patient in the C1 cluster (‘elevated CK’) was diagnosed with myocarditis. Of note, in our cohort of anti-Ku-positive systemic sclerosis (SSc) patients we found that the positivity for this rare antibody was invariably associated with myocardial inflammation. We indeed performed a retrospective review of anti-Ku-positive patients affected by SSc according to European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) 2013 criteria2 followed-up at two referral centres for SSc. We routinely performed anti-Ku in all SSc patients without any detected positivity for …
Published: 2019

46. Life-threatening arrhythmias in a scleroderma patient: the role of myocardial inflammation in arrhythmic outburst

Author: G. De Luca, Gemma Pelargonio, Francesca Augusta Gabrielli, Gianfranco Ferraccioli, Filippo Crea, Antonio Maria Leone, Frediano Inzani, Silvia Laura Bosello, De Luca, Giacomo., Bosello, S., Leone, A. M., Gabrielli, F., Pelargonio, G., Inzani, F., Crea, F., and Ferraccioli, G.
Subjects: Adult, medicine.medical_specialty, Settore MED/16 - REUMATOLOGIA, systemic sclerosis, Immunology, 030204 cardiovascular system & hematology, Scleroderma, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Internal medicine, medicine, Immunology and Allergy, Humans, 030203 arthritis & rheumatology, Scleroderma, Systemic, medicine.diagnostic_test, business.industry, Myocardium, Myocardial inflammation, Magnetic resonance imaging, Arrhythmias, Cardiac, General Medicine, medicine.disease, Magnetic Resonance Imaging, Anesthesia, Cardiology, Female, business
Abstract: We report the work-up, diagnosis, management, and 14-month follow-up of a 43-year-old female referred to our attention in December 2013 for evaluation of her long-standing (13 years) anti-Scl70+ sy...
Published: 2016

47. Relationship Between Ventricular Arrhythmias, Conduction Disorders, and Myocardial Fibrosis in Patients With Systemic Sclerosis

Author: Giacomo De Luca, Corrado Campochiaro, Lorenzo Dagna, Giulio Cavalli, De Luca, Giacomo, Campochiaro, Corrado, Cavalli, Giulio, and Dagna, Lorenzo
Subjects: Tachycardia, medicine.medical_specialty, Conduction disorders, Magnetic Resonance Imaging, Cine, 030204 cardiovascular system & hematology, Risk Assessment, Scleroderma, 03 medical and health sciences, 0302 clinical medicine, Cardiac Conduction System Disease, Rheumatology, Internal medicine, medicine, Humans, In patient, 030203 arthritis & rheumatology, Scleroderma, Systemic, medicine.diagnostic_test, business.industry, Myocardium, Magnetic resonance imaging, Prognosis, medicine.disease, Fibrosis, Tachycardia, Ventricular, Cardiology, Myocardial fibrosis, medicine.symptom, business, Cardiac magnetic resonance
Published: 2018

48. Long-term efficacy of B cell depletion therapy on lung and skin involvement in diffuse systemic sclerosis

Author: Francesco Danza, Silvia Laura Bosello, Giacomo De Luca, M. Rucco, Tommaso Pirronti, Gianfranco Ferraccioli, Matteo Falcione, G. Berardi, Bosello, Silvia Laura, De Luca, Giacomo, Rucco, Manuela, Berardi, Giorgia, Falcione, Matteo, Danza, Fm, Pirronti, Tommaso, and Ferraccioli, Gianfranco
Subjects: Adult, Male, medicine.medical_specialty, Settore MED/16 - REUMATOLOGIA, Time Factors, CD20 depletion therapy, Lung involvement, Gastroenterology, Severity of Illness Index, Pulmonary function testing, FEV1/FVC ratio, Antibodies, Monoclonal, Murine-Derived, B-Cell Depletion Therapy, Rheumatology, DLCO, Internal medicine, medicine, Humans, Restrictive lung disease, Cyclophosphamide, Lung, Settore MED/36 - DIAGNOSTICA PER IMMAGINI E RADIOTERAPIA, Skin, B cells, B-Lymphocytes, Scleroderma, Systemic, Skin fibrosis, business.industry, respiratory system, Middle Aged, medicine.disease, Antigens, CD20, respiratory tract diseases, Surgery, Respiratory Function Tests, Anesthesiology and Pain Medicine, medicine.anatomical_structure, Treatment Outcome, Systemic sclerosis, Rituximab, Female, business, Tomography, X-Ray Computed, medicine.drug, Follow-Up Studies
Abstract: Objectives To assess the long-term efficacy and safety of single and multiple courses of rituximab therapy in systemic sclerosis (SSc) patients with and without lung disease. Methods A total of 20 SSc patients with a diffuse disease were treated with rituximab. At baseline and during follow-up the lung involvement was evaluated with pulmonary function tests (FVC and DLCO) and with lung high-resolution computed tomography (HRCT). Results The skin score, activity, and severity indices improved significantly after 12 months and at final follow-up compared to baseline. After 12 months, there was a significant increase of FVC and TLC compared to baseline ( p = 0.024 and p = 0.005, respectively), while the mean DLCO value remained stable. Considering the last available follow-up in six patients with restrictive lung disease at baseline, two patients (33.3%) experienced an increase of more than 10% of FVC, one patient had a decrease of FVC >10%, while in three patients FVC remained stable (50%). After the mean follow-up of 48.5 ± 20.4 months, among the patients with normal lung parameters at baseline, FVC remained stable in 12 (85.7%) and in one patient (14.3%) it increased by more than 10%. At the final follow-up, the alveolar and interstitial HRCT scores remained stable in more than 80% of patients, both in patients with and without restrictive lung disease at baseline. Conclusions Anti-CD20 B cell depletion therapy is effective on skin involvement but seems also to preserve the pulmonary function, as supported by a stable or improved FVC and stable interstitial score, suggesting a possible role of rituximab as a modifying therapy overall in early diffuse SSc.
Published: 2014

49. B cells in systemic sclerosis: a possible target for therapy

Author: Gianfranco Ferraccioli, Silvia Laura Bosello, Barbara Tolusso, Gigliola Sica, Giacomo De Luca, Cristiana Angelucci, Gina Lama, Bosello, S., De Luca, Giacomo., Tolusso, B., Lama, G., Angelucci, C., Sica, G., and Ferraccioli, G.
Subjects: Immunology, Naive B cell, medicine.disease_cause, Lymphocyte Activation, Lymphocyte Depletion, Autoimmunity, Anti-CD20, Antibodies, Monoclonal, Murine-Derived, Mice, Fibrosis, Genetic model, medicine, Immunology and Allergy, Animals, Humans, Molecular Targeted Therapy, skin and connective tissue diseases, Autoimmune disease, CD20, B cells, B-Lymphocytes, Clinical Trials as Topic, Scleroderma, Systemic, integumentary system, biology, business.industry, medicine.disease, Mice, Mutant Strains, Disease Models, Animal, biology.protein, Systemic sclerosis, Cytokines, Rituximab, Settore BIO/17 - ISTOLOGIA, Antibody, business, medicine.drug
Abstract: Systemic sclerosis (SSc) is an autoimmune disease characterized by excessive extracellular matrix (ECM) deposition in the skin and other visceral organs and it is associated with immune activation characterized by autoantibody production, release of various cytokines and T-lymphocyte activation. Several recent lines of evidence in animal models and in SSc patients indicate a potential role for B cells in the SSc. B cells have arisen as a possible player in tissue fibrosis in some experimental models and, since IL-6 produced by B cells, along with TGF-β, may induce matrix synthesis and less collagen degradation, targeting B cells could be one way to reduce ECM deposition and reduce the inflammatory background. Both SSc patients and tight-skin mice, a genetic model of SSc, have intrinsic B-cell abnormalities characterized by chronic B-cell activation. SSc patients present an increased number of naïve B cells and an activation of memory B cells, despite a reduction in their number. B cells from SSc patients exhibit increased expression of CD19. Remarkably, CD19 loss or B-cell depletion using antimouse CD20 antibody suppresses the development of skin hyperplasia and autoimmunity in tight-skin mice. Additionally, recent studies revealed a possible beneficial effect of anti-human CD20 antibody (Rituximab) therapy on skin fibrosis and lung involvement in SSc patients. These studies reported also the safety of Rituximab in SSc patients. All these findings suggest a possible role of antiCD20 treatment in SSc patients. © 2011 Elsevier B.V.
Published: 2011

50. The clinical phenotype of Systemic Sclerosis patients with anti-PM/Scl antibodies: results from the EUSTAR cohort

Author: Vanessa Smith, Ellen De Langhe, Elisabetta Zanatta, Jorge Rojas-Serrano, Christopher P. Denton, Roger Hesselstrand, Lorenzo Cavagna, Franco Franceschini, Montserrat-Ixchel Gonzalez-Perez, Angela Ceribelli, Konstantinos Triantafyllias, Marie-Elise Truchetet, Federica Furini, Giacomo De Luca, Alessio Furloni, Francesco Del Galdo, Yannick Allanore, Ilaria Cavazzana, Hadi Poormoghim, Corrado Campochiaro, G. Abignano, M. G. Lazzaroni, Francesca Ingegnoli, Paolo Airò, Silvia Bellando-Randone, Emiliano Marasco, Eugenia Bertoldo, Enrico Colombo, Eric Hachulla, S. Zingarelli, Oliver Distler, Jeska DeVries-Bouwstra, Simone Barsotti, Lazzaroni, Maria-Grazia, Marasco, Emiliano, Campochiaro, Corrado, DeVries-Bouwstra, Jeska, Gonzalez-Perez, Montserrat-Ixchel, Rojas-Serrano, Jorge, Hachulla, Eric, Zanatta, Elisabetta, Barsotti, Simone, Furini, Federica, Triantafyllias, Konstantino, Abignano, Giuseppina, Truchetet, Marie-Elise, De Luca, Giacomo, De Langhe, Ellen, Hesselstrand, Roger, Ingegnoli, Francesca, Bertoldo, Eugenia, Smith, Vanessa, Bellando-Randone, Silvia, Poormoghim, Hadi, Colombo, Enrico, Ceribelli, Angela, Furloni, Alessio, Zingarelli, Stefania, Cavazzana, Ilaria, Franceschini, Franco, Del Galdo, Francesco, Denton, Christopher P, Cavagna, Lorenzo, Distler, Oliver, Allanore, Yannick, and Airò, Paolo
Subjects: Adult, Male, Myositis and muscle disease, medicine.medical_specialty, Scleroderma Renal Crisis, Laboratory Diagnosis, Systemic scleroderma, behavioral disciplines and activities, Gastroenterology, Scleroderma, Rheumatology, Calcinosis, Internal medicine, Scleroderma and related disorders, Myositis and muscle disease, Autoantigens and Autoantibodies, Biomarkers, Laboratory Diagnosis, medicine, Humans, Pharmacology (medical), autoantigens and autoantibodies, biomarkers, laboratory diagnosis, myositis and muscle disease, scleroderma and related disorders, Autoantibodies, Europe, Exoribonucleases, Exosome Multienzyme Ribonuclease Complex, Female, Middle Aged, Phenotype, Retrospective Studies, Scleroderma, Systemic, Registries, skin and connective tissue diseases, integumentary system, business.industry, Systemic, Autoantigens and Autoantibodies, Autoantibody, Interstitial lung disease, Cancer, Dermatomyositis, medicine.disease, Scleroderma and related disorders, Cohort, business, Biomarkers
Abstract: Objective To evaluate clinical associations of anti-PM/Scl antibodies in patients with SSc in a multicentre international cohort, with particular focus on unresolved issues, including scleroderma renal crisis (RC), malignancies, and functional outcome of interstitial lung disease (ILD). Methods (1) Analysis of SSc patients from the EUSTAR database: 144 anti-PM/Scl+ without SSc-specific autoantibodies were compared with 7202 anti-PM/Scl−, and then to 155 anti-Pm/Scl+ with SSc-specific antibodies. (2) Case–control study: additional data were collected for 165 anti-PM/Scl+ SSc patients (85 from the EUSTAR registry) and compared with 257 anti-PM/Scl− SSc controls, matched for sex, cutaneous subset, disease duration and age at SSc onset. Results Patients with isolated anti-PM/Scl+, as compared with anti-Pm/Scl−, had higher frequency of muscle involvement, ILD, calcinosis and cutaneous signs of DM, but similar frequency of SRC and malignancies (either synchronous with SSc onset or not). The presence of muscle involvement was associated with a more severe disease phenotype. Although very frequent, ILD had a better functional outcome in cases than in controls. In patients with both anti-PM/Scl and SSc-specific antibodies, a higher frequency of typical SSc features than in those with isolated anti-PM/Scl was observed. Conclusion The analysis of the largest series of anti-PM/Scl+ SSc patients so far reported helps to delineate a specific clinical subset with muscle involvement, cutaneous DM, calcinosis and ILD characterized by a good functional outcome. SRC and malignancies do not seem to be part of this syndrome.

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