Background In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov ( NCT04381936 ). Findings Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding UK Research and Innovation (Medical Research Council) and National Institute of Health Research.

SummaryBackgroundClinical outcomes after major surgery are poorly described at the national level. Evidence of heterogeneity between hospitals and health-care systems suggests potential to improve care for patients but this potential remains unconfirmed. The European Surgical Outcomes Study was an international study designed to assess outcomes after non-cardiac surgery in Europe.MethodsWe did this 7 day cohort study between April 4 and April 11, 2011. We collected data describing consecutive patients aged 16 years and older undergoing inpatient non-cardiac surgery in 498 hospitals across 28 European nations. Patients were followed up for a maximum of 60 days. The primary endpoint was in-hospital mortality. Secondary outcome measures were duration of hospital stay and admission to critical care. We used χ2 and Fisher's exact tests to compare categorical variables and the t test or the Mann-Whitney U test to compare continuous variables. Significance was set at p<0·05. We constructed multilevel logistic regression models to adjust for the differences in mortality rates between countries.FindingsWe included 46 539 patients, of whom 1855 (4%) died before hospital discharge. 3599 (8%) patients were admitted to critical care after surgery with a median length of stay of 1·2 days (IQR 0·9–3·6). 1358 (73%) patients who died were not admitted to critical care at any stage after surgery. Crude mortality rates varied widely between countries (from 1·2% [95% CI 0·0–3·0] for Iceland to 21·5% [16·9–26·2] for Latvia). After adjustment for confounding variables, important differences remained between countries when compared with the UK, the country with the largest dataset (OR range from 0·44 [95% CI 0·19–1·05; p=0·06] for Finland to 6·92 [2·37–20·27; p=0·0004] for Poland).InterpretationThe mortality rate for patients undergoing inpatient non-cardiac surgery was higher than anticipated. Variations in mortality between countries suggest the need for national and international strategies to improve care for this group of patients.FundingEuropean Society of Intensive Care Medicine, European Society of Anaesthesiology.

isrctn.org Identifier: ISRCTN04386758.

Among patients undergoing noncardiac surgery, peak postoperative hsTnT during the first 3 days after surgery was significantly associated with 30-day mortality. Elevated postoperative hsTnT without an ischemic feature was also associated with 30-day mortality.

Objective-To identify an appropriate diagnostic tool for the early diagnosis of Acute Traumatic Coagulopathy (ATC) and validate this modality through prediction of transfusion requirements in trauma hemorrhage. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Design-Prospective observational cohort study Setting-Level 1 trauma centre Europe PMC Funders Group Europe PMC Funders Author Manuscripts Europe PMC Funders Author ManuscriptsPatients-Adult trauma patients who met the local criteria for full trauma team activation. Exclusion criteria included emergency department (ED) arrival >2 hours after injury, >2000ml of intravenous fluid before ED arrival or transfer from another hospital. Interventions-NoneMeasurements-Blood was collected on arrival in ED and analysed with laboratory prothrombin time (PT), point of care (PoC) PT and rotational thromboelastometry (ROTEM). Prothrombin ratio (PTr) was calculated and ATC defined as laboratory PTr>1.2. Transfusion requirements were recorded for the first 12 hours following admission.Main Results-300 patients were included in the study. Laboratory PT results were available at median 78 (62-103) minutes. PoC PTr had reduced agreement with laboratory PTr in patients with ATC, with 29% false negative results. In ATC the ROTEM Clot Amplitude at 5 minutes (CA5) was diminished by 42% and this persisted throughout clot maturation. ROTEM clotting time was not significantly prolonged. A CA5 threshold ≤35mm had a detection rate of 77% for ATC with a false positive rate of 13%. Patients with CA5 ≤35mm were more likely to receive red cell (46% vs 17%, p<0.001) and plasma (37% vs 11%, p<0.001) transfusions. The CA5 could identify patients who would require massive transfusion (detection rate of 71%, vs 43% for PTr >1.2, p<0.001).Conclusions-In trauma hemorrhage PTr is not rapidly available from the laboratory and PoC devices can be inaccurate. ATC is functionally characterised by a reduction in clot strength. With a threshold of CA5 ≤35mm ROTEM can identify ATC at 5 minutes and predict the need for massive transfusion.