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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Foot infections are common among diabetic patients with peripheral neuropathy and/or peripheral arterial disease, and it can be the pivotal event leading to a minor or major amputation of the lower extremity. Treatment of diabetic foot infections, especially deep-seated ones, remains challenging, in part because impaired blood perfusion and the presence of biofilms can impair the effectiveness of systemic antibiotics. The local application of antibiotics is an emerging field in the treatment of diabetic foot infections, with demonstrable advantages. These include delivery of high concentrations of antibiotics in the affected area, limited systemic absorption, and thus negligible side effects. Biodegradable vehicles, such as calcium sulfate beads, are the prototypical system, providing a good elution profile and the ability to be impregnated with a variety of antibiotics. These have largely superseded the nonbiodegradable vehicles, but the strongest evidence available is for calcium bead implantation for osteomyelitis management. Natural polymers, such as collagen sponge, are an emerging class of delivery systems, although thus far, data on diabetic foot infections are limited. There is recent interest in the novel antimicrobial peptide pexiganan in the form of cream, which is active against most of the microorganisms isolated in diabetic foot infections. These are promising developments, but randomized trials are required to ascertain the efficacy of these systems and to define the indications for their use. Currently, the role of topical antibiotic agents in treating diabetic foot infections is limited and outside of routine practice.