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.

Higher circulating 25(OH)D was related to a statistically significant, substantially lower colorectal cancer risk in women and non-statistically significant lower risk in men. Optimal 25(OH)D concentrations for colorectal cancer risk reduction, 75-100 nmol/L, appear higher than current IOM recommendations.

Several definitions for pancreatic leakage after pancreaticodoudenectomy exist, and the reported range of 2-50% underscores this variation. The goal was to determine if drain data alone was predictive of a leak and validate International Study Group on Pancreatic Fistula (ISGPF) leak criteria. Participating surgeons entered de-identified data into a web-based database designed to collect Whipple-related data. Definitions used were the ISGPF definition, > or = 3 days, amylase 3x normal; and Sarr's definition, > or = 5 days, amylase 5x normal, > 30 ml. We compared how well these two definitions were at detecting a leak and its complications. There were 1,507 cases submitted from 16 international institutions. A pancreaticoduodenectomy (PPPD) was performed in 76.2%. Drain placement occurred in 98.0%. Using the ISGPF definition, the pancreatic leak rate was 26.7 and 14.3% with the Sarr definition. There were more grades A and B leaks detected by the ISGPF definition. Both determined grade C leaks equally. Both definitions correlated with an increased length of stay (LOS), need for percutaneous drains, reoperation, and delayed gastric emptying (DGE). Neither was associated with an increased risk of intensive care unit (ICU) stay or 30-day mortality. The ISGPF was able to capture more patients with clinically relevant leaks than Sarr's criteria; however, the ability to detect a leak by drain data alone is imperfect.

Writing Committee for the REMAP-CAP Investigators IMPORTANCE The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive.OBJECTIVE To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTSThe ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021. INTERVENTIONSThe immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916). MAIN OUTCOMES AND MEASURESThe primary ordinal end point was organ support-free days (days alive and free of intensive care unit-based organ support) up to day 21 (range, −1 to 21 days; patients who died were assigned -1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support-free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support-free days; cardiovascular support-free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events. RESULTS Among the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support-free days was 0 (IQR, -1 to 16) in the convalescent plasma group and 3 (IQR, -1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (OR <1.2) was 99.4% for the convalescent plasma group compared with the no convalescent plasma group. The treatment effects were consistent across the primary outcome and the 11...

Objective: The aim of this study was to test the efficacy of technology-based weight loss interventions for endometrial cancer (EC) survivors with obesity. Methods: EC survivors with obesity (n 5 196) from three medical centers completed assessments for knowledge of obesity as a risk for EC and interest in weight management. Forty-one women were randomized to a 6-month intervention: telemedicine with Wi-Fi scales, text messaging (texting), or enhanced usual care (EUC). Changes in anthropometrics and psychosocial measures were analyzed. Results: One-third of survey participants lacked awareness that obesity increased the risk of EC, and 40% misclassified their body mass. There were no significant differences in weight loss across interventions (mean 5 24.4 kg, SD 5 6.5 kg). Telemedicine showed improvements in physical health and cancerrelated body image (Ps 5 0.04) compared to texting and in sexual functioning compared to EUC (P 5 0.03). Total physical activity was increased in EUC compared with telemedicine (P 5 0.01), and vigorous physical activity was increased in EUC compared with both interventions (P 5 0.01-0.03); walking significantly increased in texting compared with telemedicine (P 5 0.02). Conclusions: Technology-based lifestyle interventions in EC survivors with obesity were accessible and resulted in weight loss and improved quality of life. EUC also produced weight loss, demonstrating a potential for beginning weight management with information on specific diet and exercise goals.