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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Increased levels of a number of immunomodulatory cytokines relative to IL-12p70 in this Caucasian SLE patient population are seen in patients with renal involvement and are associated with increased accrual of damage at the 5-year follow-up.

ObjectivesTo describe the baseline characteristics of SLE patients requiring biologic therapy in the UK and to explore short term efficacy and infection rates associated with rituximab (RTX) use.MethodsPatients commencing biologic therapy for refractory SLE and who consented to join BILAG-BR were analysed. Baseline characteristics, disease activity (BILAG 2004/SLEDAI-2K) and rates of infection over follow-up were analysed. Response was defined as loss of all A and B BILAG scores to ⩽ 1 B score with no new A/B scores in other organ systems at 6 months.ResultsTwo hundred and seventy SLE patients commenced biologic therapy from September 2010 to September 2015, most commonly RTX (n = 261). Two hundred and fifty (93%) patients were taking glucocorticoids at baseline at a median [interquartile range (IQR)] oral dose of 10 mg (5–20 mg) daily. Response rates at 6 months were available for 68% of patients. The median (IQR) BILAG score was 15 (10–23) at baseline and 3 (2–12) at 6 months (P < 0.0001). The median (IQR) SLEDAI-2K reduced from 8 (5–12) to 4 (0–7) (P < 0.001). Response was achieved in 49% of patients. There was also a reduction in glucocorticoid use to a median (IQR) dose of 7.5 mg (5–12 mg) at 6 months (P < 0.001). Serious infections occurred in 26 (10%) patients, being more frequent in the first 3 months post-RTX therapy. A higher proportion of early infections were non-respiratory (odds ratio = 1.98, 95% CI: 0.99, 3.9; P = 0.049).ConclusionRTX is safe and is associated with improvement in disease activity in refractory SLE patients with concomitant reductions in glucocorticoid use. Early vigilance for infection post-infusion is important to further improve treatment risks and benefits.

Endothelial microparticles (EMPs) are endothelium-derived submicron vesicles that are released in response to diverse stimuli and are elevated in cardiovascular disease, which is correlated with risk factors. This study investigates the effect of EMPs on endothelial cell function and dysfunction in a model of free fatty acid (FFA) palmitate-induced oxidative stress. EMPs were generated from TNF-α-stimulated HUVECs and quantified by using flow cytometry. HUVECs were treated with and without palmitate in the presence or absence of EMPs. EMPs were found to carry functional eNOS and to protect against oxidative stress by positively regulating eNOS/Akt signaling, which restored NO production, increased superoxide dismutase and catalase, and suppressed NADPH oxidase and reactive oxygen species (ROS) production, with the involvement of NF-erythroid 2-related factor 2 and heme oxygenase-1. Conversely, under normal conditions, EMPs reduced NO release and increased ROS and redox-sensitive marker expression. In addition, functional assays using EMP-treated mouse aortic rings that were performed under homeostatic conditions demonstrated a decline in endothelium-dependent vasodilatation, but restored the functional response under lipid-induced oxidative stress. These data indicate that EMPs harbor functional eNOS and potentially play a role in the feedback loop of damage and repair during homeostasis, but are also effective in protecting against FFA-induced oxidative stress; thus, EMP function is reflected by the microenvironment.—Mahmoud, A. M., Wilkinson, F. L., McCarthy, E. M., Moreno-Martinez, D., Langford-Smith, A., Romero, M., Duarte, J., Alexander, M. Y. Endothelial microparticles prevent lipid-induced endothelial damage via Akt/eNOS signaling and reduced oxidative stress.

Background: Supine or prone positioning of the patient on the gantry table is the current standard of care for CT-guided lung biopsy; positioning biopsy side down was hypothesized to be associated with lower pneumothorax rate.Purpose: To assess the effect of positioning patients biopsy side down during CT-guided lung biopsy on the incidence of pneumothorax, chest drain placement, and hemoptysis. Materials and Methods:This retrospective study was performed between January 2013 and December 2016 in a tertiary referral oncology center. Patients undergoing CT-guided lung biopsy were either positioned in (a) the standard prone or supine position or (b) the lateral decubitus position with the biopsy side down. The relationship between patient position and pneumothorax, drain placement, and hemoptysis was assessed by using multivariable logistic regression models.Results: A total of 373 consecutive patients (mean age 6 standard deviation, 68 years 6 10), including 196 women and 177 men, were included in the study. Among these patients, 184 were positioned either prone or supine depending on the most direct path to the lesion and 189 were positioned biopsy side down. Pneumothorax occurred in 50 of 184 (27.2%) patients who were positioned either prone or supine and in 20 of 189 (10.6%) patients who were positioned biopsy side down (P , .001). Drain placement was required in 10 of 184 (5.4%) patients who were positioned either prone or supine and in eight of 189 (4.2%) patients who were positioned biopsy side down (P = .54). Hemoptysis occurred in 19 of 184 (10.3%) patients who were positioned prone or supine and in 10 of 189 (5.3%) patients who were positioned biopsy side down (P = .07). Prone or supine patient position (P = .001, odds ratio [OR] = 2.7 [95% confidence interval {CI}: 1.4, 4.9]), emphysema along the needle path (P = .02, OR = 2.1 [95% CI: 1.1, 4.0]), and lesion size (P = .02, OR = 1.0 [95% CI: 0.9, 1.0]) were independent risk factors for developing pneumothorax. Conclusion:Positioning a patient biopsy side down for percutaneous CT-guided lung biopsy reduced the incidence of pneumothorax compared with the supine or prone position.