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, 1...

Background Preliminary reports suggest a hypercoagulable state in COVID-19. Deep vein thrombosis (DVT) is perceived as a frequent finding in hospitalized COVID-19 patients, but data describing the prevalence of DVT are lacking. Objectives We aimed to report the prevalence of DVT in COVID-19 patients in general wards, blinded to symptoms/signs of disease, using lower extremities duplex ultrasound (LEDUS) in random patients. We tested the association of DVT with clinical, laboratory and inflammatory markers and also reported on the secondary endpoint of in-hospital mortality. Patients/Methods n = 263 COVID-19 patients were screened with LEDUS between March 01, 2020 and April 05, 2020 out of the overall n = 1012 admitted with COVID-19. Results DVT was detected in n = 67 screened patients (25.5%), n = 41 patients (15.6%) died during the index hospitalization. Multiple logistic regression demonstrated that only C-reactive protein (odds ratio 1.009, 95% CI 1.004-1.013, p < 0.001) was independently associated with the presence of DVT at LEDUS. Both age (odds ratio 1.101, 95% CI 1.054-1.150, p < 0.001) and C-reactive protein (odds ratio 1.012, 95% CI 1.006-1.018, p < 0.001) were instead significantly independently associated with in-hospital mortality. Conclusions The main study finding is that DVT prevalence in COVID-19 patients admitted to general wards is 25.5%, suggesting it may be reasonable to screen COVID-19 patients for this potentially severe but treatable complication, and that inflammation, measured with serum C-reactive protein, is the main variable associated with the presence of DVT, where all other clinical or laboratory variables, age or D-dimer included, are instead not independently associated with DVT.

With stress echo (SE) 2020 study, a new standard of practice in stress imaging was developed and disseminated: the ABCDE protocol for functional testing within and beyond CAD. ABCDE protocol was the fruit of SE 2020, and is the seed of SE 2030, which is articulated in 12 projects: 1-SE in coronary artery disease (SECAD); 2-SE in diastolic heart failure (SEDIA); 3-SE in hypertrophic cardiomyopathy (SEHCA); 4-SE post-chest radiotherapy and chemotherapy (SERA); 5-Artificial intelligence SE evaluation (AI-SEE); 6-Environmental stress echocardiography and air pollution (ESTER); 7-SE in repaired Tetralogy of Fallot (SETOF) ; 8-SE in post-COVID-19 (SECOV); 9: Recovery by stress echo of conventionally unfit donor good hearts (RESURGE); 10-SE for mitral ischemic regurgitation (SEMIR); 11-SE in valvular heart disease (SEVA); 12-SE for coronary vasospasm (SESPASM). The study aims to recruit in the next 5 years (2021–2025) ≥10,000 patients followed for ≥5 years (up to 2030) from ≥20 quality-controlled laboratories from ≥10 countries. In this COVID-19 era of sustainable health care delivery, SE2030 will provide the evidence to finally recommend SE as the optimal and versatile imaging modality for functional testing anywhere, any time, and in any patient.

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Background: Inflammation plays a key role in atrial fibrillation (AF). Epicardial adipose tissue around the atrial wall can influence atrial morpho-functional properties. The aim of this study was to assess whether an increased quantity and/or density of adipose tissue located around the left atrium (Fat-LA) are related to AF, independently from atrial size. Methods: eighty patients who underwent AF ablation and 80 patients without history of AF were selected. The Fat-LA mass was quantified as tissue within −190 to −30 Hounsfield Units (HU) on cardiac computed tomography angiograms (CCTA), and the mean adipose tissue attenuation was assessed. Results: Adipose tissue mass was higher in patients with AF (5.42 ± 2.94 mL) versus non-AF (4.16 ± 2.55 mL, p = 0.007), but relative fat quantity did not differ after adjusting for atrial size. Mean fat density was significantly higher in AF (−69.15 HU) versus non-AF (−76.82 HU, p < 0.0001) participants. In the logistic regression models, only the addition of mean Fat-LA attenuation led to a significant improvement of the model’s chi-square (from 22.89 of the clinical model to 31.69 of the clinical and adipose tissue attenuation model, p < 0.01) and discrimination (AUC from 0.775 to 0.829). Conclusions: Fat-LA volume is significantly greater only in absolute terms in patients with AF, but this difference does not hold after adjusting for the larger LA of AF subjects. On the contrary, a higher Fat-LA density was associated with AF, independently from LA size, providing incremental value over other variables that are associated with AF.