Summary Objectives Patients with acute respiratory distress syndrome (ARDS) due to viral infection are at risk for secondary complications like invasive aspergillosis. Our study evaluates coronavirus disease 19 (COVID‐19) associated invasive aspergillosis at a single centre in Cologne, Germany. Methods A retrospective chart review of all patients with COVID‐19 associated ARDS admitted to the medical or surgical intensive care unit at the University Hospital of Cologne, Cologne, Germany. Results COVID‐19 associated invasive pulmonary aspergillosis was found in five of 19 consecutive critically ill patients with moderate to severe ARDS. Conclusion Clinicians caring for patients with ARDS due to COVID‐19 should consider invasive pulmonary aspergillosis and subject respiratory samples to comprehensive analysis to detect co‐infection.

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...

BackgroundAcute kidney injury (AKI) is a common complication after cardiac surgery. Currently, prediction of AKI with classical tools remains uncertain. Therefore, it was the aim of the present study to evaluate two new urinary biomarkers—insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) in patients after coronary artery bypass surgery (CABG).MethodsIn a prospective cohort study, 60 consecutive patients undergoing isolated on-pump CABG were enrolled. Urine samples collected every 12 h in the postoperative course were analyzed for the product of TIMP-2 and IGFBP7. Urinary output, serum creatinine and estimated glomerular filtration rate (eGFR) were recorded simultaneously. Primary clinical endpoint was the development of AKI stage 2 or 3 according to the classification of the KDIGO within 48 h after surgery.Results48 male and 12 female patients with a mean age of 69.61 ± 8.4 years were included. 19 patients developed an AKI (31.6 %), six patients met the endpoint with AKI 2 or 3 (10 %). Urinary [TIMP-2]*[IGFBP7] increased significantly as early as 4 h after CABG in patients with AKI 2/3 (1.83 ± 2.15 vs. 0.23 ± 0.45, p < 0.05) whereas serum creatinine did not increase until 48 h after surgery. The diagnostic accuracy of [TIMP 2]*[IGFBP7] on day one after surgery for the prediction of AKI 2/3 was significantly better (sensitivity 0.89, specificity 0.81, AUC 0.817, 95 % CI 0.622–1.0 SE 0.099, p = 0.022, cut-off 0.817) than for serum creatinine (AUC 0.359, sensitivity 0.50, specificity of 0.52, cut-off value 1.17 mg/dl) and eGFR.ConclusionUrinary [TIMP-2]*[IGFBP7] represents a sensitive and specific biomarker to predict moderate to severe AKI very early after CABG. Analyses from our ongoing larger study are necessary to confirm these findings and probably increase sensitivity and specificity.