Gabriela Neira, Julia Hernández-Castañeda, Victoria Catalán, Sara Becerril, Marina Martín, Víctor Valentí, Rafael Moncada, Camilo Silva, Javier Gómez-Ambrosi, Javier Escalada, Gema Frühbeck, Amaia Rodríguez
{"title":"FNDC4 and FNDC5 Attenuate SARS-CoV-2 S1-Induced Inflammatory Responses in Human Adipose Tissue.","authors":"Gabriela Neira, Julia Hernández-Castañeda, Victoria Catalán, Sara Becerril, Marina Martín, Víctor Valentí, Rafael Moncada, Camilo Silva, Javier Gómez-Ambrosi, Javier Escalada, Gema Frühbeck, Amaia Rodríguez","doi":"10.1111/eci.70215","DOIUrl":"10.1111/eci.70215","url":null,"abstract":"<p><strong>Background: </strong>Adipose tissue is recognised as a SARS-CoV-2 reservoir and potential infection site. We herein characterised SARS-CoV-2 entry points in visceral (VAT) and subcutaneous (SAT) adipose tissue from people with obesity and determined whether the adipo-myokines FNDC4 and FNDC5 modulate SARS-CoV-2 spike glycoprotein subunit 1 (S1)-induced inflammation in adipocytes and macrophages.</p><p><strong>Methods: </strong>Plasma concentrations of FNDC4, FNDC5 and angiotensin-converting enzyme 2 (ACE2) were measured in 183 participants with obesity and normal weight. Expression of SARS-CoV-2 host cell entry receptors was analysed in paired VAT and SAT biopsies (n = 121). The effects of FNDC4 and FNDC5 on S1-induced inflammatory responses were evaluated in vitro using human visceral adipocytes and THP-1-derived macrophages.</p><p><strong>Results: </strong>Obesity was associated with higher circulating ACE2 and increased expression of SARS-CoV-2 entry receptors (ACE2, CD147, DPP4 and neuropilin-1) in VAT, whereas plasma FNDC4 and FNDC5 levels were reduced. FNDC4, FNDC5 and ACE2 co-localised with macrophage populations in VAT, and FNDC4 and FNDC5 transcripts positively correlated with genes involved in viral entry and priming. Both adipo-myokines attenuated S1-induced M1 macrophage polarisation and HMGB1 secretion and reduced HMGB1 expression in adipocytes.</p><p><strong>Conclusion: </strong>Reduced FNDC4 and FNDC5 levels in obesity may amplify SARS-CoV-2 S1-induced inflammatory responses in VAT macrophages and adipocytes.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 5","pages":"e70215"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13123202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lisa Caldera, Chiara Lovati, Alessandra Vecchié, Walter Ageno, Marco Paolo Donadini, Francesco Dentali, Flavio Tangianu, Aldo Bonaventura
{"title":"Management and Prognosis of Patients With Acute Pericarditis in the Emergency Department: A Retrospective, Single-Centre Study.","authors":"Lisa Caldera, Chiara Lovati, Alessandra Vecchié, Walter Ageno, Marco Paolo Donadini, Francesco Dentali, Flavio Tangianu, Aldo Bonaventura","doi":"10.1111/eci.70206","DOIUrl":"10.1111/eci.70206","url":null,"abstract":"<p><strong>Background: </strong>Despite being a common reason for Emergency Department (ED) admission, information about the management of acute pericarditis is limited in this setting.</p><p><strong>Methods: </strong>In this retrospective study conducted at the ED of Ospedale di Circolo in Varese (Italy) from 2019 to 2023, patients with acute pericarditis were included. The primary endpoint was the occurrence of the 12-month composite outcome (treatment failure, recurrent pericarditis, cardiac tamponade, constrictive pericarditis or death).</p><p><strong>Results: </strong>One-hundred and sixty-nine patients were included (median age 54 years, 65.1% males). Chest pain was the main symptom (96.4%). On admission, aspirin was more frequently given over non-steroidal anti-inflammatory drugs (NSAIDs), and colchicine was prescribed in 40% of patients. At discharge, more patients were prescribed ibuprofen, and colchicine prescription significantly increased to 71%. Drug doses were compliant with guidelines in a limited number of patients at admission and increased at discharge. The composite outcome occurred in 20.1% of patients (n = 34), mainly driven by recurrences (n = 18) and treatment failure. Patients with a complicated course were older, of female sex, with a larger proportion of comorbidities and higher CRP levels. Diabetes (HR 3.9, 95% CI 1.7-9.1), COPD (HR 6.2, 95% CI 2.3-17.1), recent percutaneous cardiac procedures (HR 6.5, 95% CI 2.1-19.6), and recent SARS-CoV-2 vaccination (HR 3.0, 95% CI 1.1-8.2) were independent risk factors for the composite outcome.</p><p><strong>Conclusion: </strong>A significant proportion of patients with acute pericarditis experience long-term complications. Sub-optimal adherence to guideline-recommended doses of anti-inflammatory drugs was commonly observed, suggesting an area for improvement in the management of these patients.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 5","pages":"e70206"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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