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.

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Objective: The Cor-Knot automated fastener has been used to eliminate the need for manual knot-tying in cardiac valve surgery for over a decade. We review the current literature pertaining to Cor-Knot and discuss its benefits and shortcomings with respect to cardiac valve surgery. Methods: A comprehensive literature search was conducted to identify articles discussing the use of automated fasteners and manually tied knots in the setting of cardiac valve surgery. The search terms used were "heart", "valve surgery", "cardiac", "Cor-Knot", "fastener", "automated fastener", "aortic valve", "mitral valve", "minimally invasive", and "titanium". These terms were used as keywords and, in combination, as MeSH terms to maximize the output of literature searches. Twenty-four relevant articles were identified and reviewed. Results: Current literature provides evidence to support the role of Cor-Knot in facilitating enhanced intraoperative efficacy by reducing total operation times as compared with manual knot-tying. However, studies to date fail to provide evidence for the translation of these intraoperative advantages into improved patient outcomes. Moreover, Cor-Knot is associated with a significant financial burden. Conclusion: A plethora of evidence exists to support the intraoperative advantages provided by Cor-Knot. However, the literature is yet to support its role in facilitating superior clinical outcomes as compared with manual knot tying. Larger high-quality trials and studies are required to provide evidence supporting the ongoing use of Cor-Knot in valve surgery.

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