The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset (NCT04348656). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm—relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94–1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02–1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57–0.95 and OR = 0.66, 95% CI 0.50–0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14–2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.

Expression of the intrinsic cellular caspase inhibitor XIAP is regulated primarily at the level of protein synthesis. The 5′ untranslated region harbours an Internal Ribosome Entry Site (IRES) motif that supports cap-independent translation of XIAP mRNA during conditions of cellular stress. In this study, we show that the RNA-binding protein HuR, which is known to orchestrate an antiapoptotic cellular program, stimulates translation of XIAP mRNA through XIAP IRES. We further show that HuR binds to XIAP IRES in vitro and in vivo, and stimulates recruitment of the XIAP mRNA into polysomes. Importantly, protection from the apoptosis-inducing agent etoposide by overexpression of HuR requires the presence of XIAP, suggesting that HuR-mediated cytoprotection is partially executed through enhanced XIAP translation. Our data suggest that XIAP belongs to the HuR-regulated RNA operon of antiapoptotic genes, which, along with Bcl-2, Mcl-1 and ProTα, contributes to the regulation of cell survival.

Objective To analyse the association between survival from critical illness and suicide or self-harm after hospital discharge. Design Population based cohort study using linked and validated provincial databases. Setting Ontario, Canada between January 2009 and December 2017 (inclusive). Participants Consecutive adult intensive care unit (ICU) survivors (≥18 years) were included. Linked administrative databases were used to compare ICU hospital survivors with hospital survivors who never required ICU admission (non-ICU hospital survivors). Patients were categorised based on their index hospital admission (ICU or non-ICU) during the study period. Main outcome measures The primary outcome was the composite of death by suicide (as noted in provincial death records) and deliberate self-harm events after discharge. Each outcome was also assessed independently. Incidence of suicide was evaluated while accounting for competing risk of death from other causes. Analyses were conducted by using overlap propensity score weighted, cause specific Cox proportional hazard models. Results 423 060 consecutive ICU survivors (mean age 61.7 years, 39% women) were identified. During the study period, the crude incidence (per 100 000 person years) of suicide, self-harm, and the composite of suicide or self-harm among ICU survivors was 41.4, 327.9, and 361.0, respectively, compared with 16.8, 177.3, and 191.6 in non-ICU hospital survivors. Analysis using weighted models showed that ICU survivors ( v non-ICU hospital survivors) had a higher risk of suicide (adjusted hazards ratio 1.22, 95% confidence interval 1.11 to 1.33) and self-harm (1.15, 1.12 to 1.19). Among ICU survivors, several factors were associated with suicide or self-harm: previous depression or anxiety (5.69, 5.38 to 6.02), previous post-traumatic stress disorder (1.87, 1.64 to 2.13), invasive mechanical ventilation (1.45, 1.38 to 1.54), and renal replacement therapy (1.35, 1.17 to 1.56). Conclusions Survivors of critical illness have increased risk of suicide and self-harm, and these outcomes were associated with pre-existing psychiatric illness and receipt of invasive life support. Knowledge of these prognostic factors might allow for earlier intervention to potentially reduce this important public health problem.

There is currently a lack of high-quality data on the use of remifentanil in the ED. Physicians should exert caution when using remifentanil in the absence of published standardised dosing protocols in light of frequently reported paediatric respiratory depression. However, PSA efficacy combined with faster recovery times merit ongoing investigations into its use.

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