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.

Liver homing of clinical grade Tregs after therapeutic infusion in patients with autoimmune hepatitis Tregs suppress proliferation and cytokine production of T effector cells & prevent autoimmunity Autologous Tregs home to inflamed autoimmune livers after infusion without side effects Autoimmune hepatitis patients Tregs express CXCR3 chemokine receptor and are functional Highlights • Tregs from patients with autoimmune hepatitis are suppressive, possess functional markers CD39 and CTLA-4, and express CXCR3. • Treg infusion in autoimmune liver disease is safe without any side effects. • 22-44% of infused Tregs home to and were retained in the livers of patients with autoimmune hepatitis for up to 72 hours.

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Summary: Navicular disease (also referred to as palmar foot syndrome or navicular syndrome, although not completely the same) causes lameness in many horses of all activity groups.The objective of this study was to compare clodronate efficacy at improving lameness grade in horses with clinical signs of navicular disease to that of horses given placebo. A randomized, multi-center, double-blinded clinical field study was conducted on 146 horses with forelimb lameness due to navicular disease. Navicular disease was confirmed by lameness examination (with diagnostic nerve blocks) and radiography of the affected distal forelimb(s). At study initiation, treated horses received 1.4 mg/kg clodronate disodium IM, and control (placebo) horses received a corresponding IM volume of 0.9 % saline. Primary effectiveness was evaluated at Day 56 using a lameness grading scale, with positive response defined as improvement by at least 1 grade in the limb with the most apparent lameness, with no worsening of the lameness grade (compared to baseline) in the contralateral forelimb. Positive response rates at Days 28 and 180 were also recorded. On Day 56, 75 % of horses in the clodronate group were considered showing a positive response, versus only 3 % in the placebo group (p = 0.003). Of the 86 horses treated with clodronate, 8 horses had an improvement of 3 lameness grades, 45 horses improved by 2 lameness grades and 16 horses improved by one lameness grade. The clodronate positive response rate remained high through Day 180 (65 %). Adverse events (primarily abdominal pain) were generally few, mild, and transient. In this study, clodronate disodium was demonstrated to be safe and effective in reducing the clinical signs of lameness associated with navicular syndrome.