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Metabolism in males and females is distinct. Differences are usually linked to sexual reproduction, with circulating signals (e.g. hormones) playing major roles. By contrast, sex differences prior to sexual maturity and intrinsic to individual metabolic tissues are less understood. We analyzedDrosophila melanogasterlarvae and find that males store more fat than females, the opposite of the sexual dimorphism in adults. We show that metabolic differences are intrinsic to the major fat storage tissue, including many differences in the expression of metabolic genes. Our previous work identified fat storage roles for Spenito (Nito), a conserved RNA-binding protein and regulator of sex determination. Nito knockdown specifically in the fat storage tissue abolished fat differences between males and females. We further show that Nito is required for sex-specific expression of the master regulator of sex determination, Sex-lethal (Sxl). “Feminization” of fat storage cells via tissue-specific overexpression of a Sxl target gene made larvae lean, reduced the fat differences between males and females, and induced female-like metabolic gene expression. Altogether, this study supports a model in which Nito autonomously controls sexual dimorphisms and differential expression of metabolic genes in fat cells in part through its regulation of the sex determination pathway.

IntroductionCardiovascular diseases are highly prevalent amongst the UK population, and the quality of care is being reduced due to accessibility and resource issues. Increased implementation of digital technologies into the cardiovascular care pathway has enormous potential to lighten the load on the NHS, however, it is not possible to adopt this shift without embedding the perspectives of service users and clinicians.Methods and AnalysisA series of qualitative studies will be carried out with the aim of developing a stakeholder-led perspective on the implementation of digital technologies to improve holistic diagnosis of heart disease. Focus groups will be carried out with 20 people with lived experience of heart disease, and interviews will be carried out with 10 clinicians with experience of diagnosing heart diseases. The data will be analysed using an inductive thematic analysis approach.Ethics and DisseminationThis study received ethical approval from the Sciences and Technology Cross Research Council at the University of Sussex. The findings will be disseminated through conference presentations, peer-reviewed publications and to the study participants.Strengths and LimitationsThe study materials have been informed by patient advisory boards, meaning they are sensitive to the experiences of the participants and the clinicians that will be recruited.The study will allow an in-depth understanding of the attitudes and experience of people with lived experience of heart disease and clinicians with experience of diagnosing heart disease.The use of an online research platform for participant recruitment will disadvantage those less comfortable using online resources. This may include those living in deprived areas without access to high quality technologies (which disproportionately excludes ethnic minority groups) and clinical populations with comorbidities that prevent the use of certain technologies, such as visual, auditory, physical, or learning impairments.The use of thematic analysis will not be free from the influence of the researcher’s personal experience and knowledge

The Nancy team is supported by the RHU Fight-HF, a public grant overseen by the French National Research Agency (ANR) as part of the second 'Investissements d'Avenir' programme (reference: ANR-15-RHUS-0004), by the French PIA project 'Lorraine Université d'Excellence' (reference: ANR-15-IDEX-04-LUE), the ANR FOCUS-MR (reference: ANR-15-CE14-0032-01), ERA-CVD EXPERT (reference: ANR-16-ECVD-0002-02), the Contrat de Plan Etat Lorraine IT2MP, and FEDER Lorraine. Aims: In ambulatory patients with chronic heart failure (HF), congestion and decongestion assessment may be challenging. The aim of this study is to assess the value of lung ultrasound (LUS) in outpatients with HF in characterizing decompensation and recompensation, and in outcomes prediction. Methods and results: Heart failure outpatients attended to establish HF decompensation were included. LUS was blindly performed at baseline (LUS1) and at clinical recompensation (LUS2). B-lines were counted in eight scanned areas. Diagnosis of no HF decompensation vs. right-sided, left-sided, or global HF decompensation, and patients' management were performed by physicians blinded to LUS1. Outcome was the composite of all-cause death or HF-related hospitalization. Two hundred and thirty-three suspicions of HF decompensation were included in 187 patients (71.4 ± 11.3 years, 66.8% men). Mean B-line (LUS1) was 17.6 ± 11.2 vs. 3.7 ± 4.5 for episodes with and without HF decompensation, respectively (P < 0.001). Global HF decompensation showed the highest number of B-lines (20.6 ± 11), followed by left-sided (19.7 ± 11.6) and right-sided (13.5 ± 9.8). B-lines declined to 6.9 ± 6.7 (LUS2) (P < 0.001 vs. LUS1) after treatment, within a mean time of 24.2 ± 23.7 days [median 13.5 days (interquartile range 6-40)]. B-lines were significantly associated with the composite endpoint at 30 days (hazard ratio [HR] 1.04 [95% confidence interval 1.01-1.07], P = 0.02), but not at 60 (P = 0.22) or 180 days (P = 0.54). In multivariable analysis, B-line number remained as an independent predictor of the composite endpoint at 30 days, [HR 1.04 (1.01-1.07), P = 0.014], with a 4% increase risk per B-line added. B-lines correlated significantly with CA125 (R = 0.30, P = 0.001). Conclusions: Lung ultrasound supports the diagnostic work-up of congestion and decongestion in chronic HF outpatients and identifies patients at high risk of short-term events.

Resumen Introduccion y objetivos La utilidad de la ecografia pulmonar (EP) en la insuficiencia cardiaca (IC) aguda esta bien definida, pero no asi en la IC cronica. Este estudio investigo el valor pronostico de la EP en pacientes estables con IC cronica. Metodos Se incluyo a pacientes ambulatorios consecutivos con visita programada en una unidad de IC. La EP se realizo in situ, con los datos clinicos enmascarados, y evaluo 8 areas toracicas. La suma de lineas B en todas las areas pulmonares y los cuartiles de dicha adicion se utilizaron para los analisis de regresion lineal y de Cox. Los objetivos principales fueron el compuesto de muerte por cualquier causa u hospitalizacion por IC y mortalidad por cualquier causa. Resultados Se incluyo a 577 individuos (edad, 69 ± 12 anos; el 72% varones). La media de lineas B fue de 5 ± 6. Durante un seguimiento de 31 ± 7 meses, en 157 pacientes se produjo el resultado compuesto y 111 fallecieron. Tener ≥ 8 lineas B (Q4) doblo el riesgo de padecer el evento compuesto (p Conclusiones La EP identifico a pacientes con IC cronica estable y alto riesgo de muerte u hospitalizacion por IC.

Background Inconsistent and controversial results have been reported about the association of quality of life (QoL) and left ventricular ejection fraction (LVEF) in patients with heart failure (HF). The 2021 universal definition of HF specifically describes the criteria for the patients with HF and improved LVEF (HFimpEF): HF with a baseline LVEF ≤40%, a ≥10 point increase from baseline LVEF, and a second measurement of LVEF >40%. Purpose 1) To assess whether patients with HF and reduced LVEF (HFrEF) at first visit in an outpatient HF Clinic that fulfil the HFimpEF criteria one year later presented a higher improvement in QoL assessed by the Minnesota Living With Heart Failure Questionnaire (MLWHFQ) than those patients that did not fulfil HFimpEF criteria. 2) To assess the prognostic role of QoL on outcomes in HFimpEF patients. Methods In a prospective registry of real-life HF outpatients LVEF and QoL evaluated by MLWHFQ were assessed at first visit at the HF Clinic and at one year of follow-up. Results From August 2001 to August 2021, baseline and one year LVEF and MLWFQ scores were available in 1040 patients with an initial LVEF ≤40%. Table 1 shows baseline demographic and clinical characteristics of patients. In summary, mean age was 65.2±11.7 years, 75.9% of the patients were men, the main aetiology was ischaemic heart disease (52.9%) and patients were mostly in New York heart Association (NHYA) class II (71.1%) and III (21.6%). Baseline LVEF was 28.5% ± 7.3 and baseline MLWHFQ score was 30.2±19.5. At one year, mean LVEF increased to 38.0±12.2 while MLWHFQ scores improved to 17.4±16.0. There were 361 patients that fulfilled the HFimpEF criteria (34.7%). These patients significantly and markedly improved both LVEF (from 28.7±6.6 to 50.9±7.6, p Conclusions QoL improved both in patients with and without HFimpEF criteria, and QoL perception at one year was similar in both groups, suggesting the influence of other factors other than LVEF in QoL perception. QoL at one year revealed to be superior to QoL changes from baseline from the prognostic point of view. Funding Acknowledgement Type of funding sources: None.

Background During two decades we have been screening fragility in outpatients with heart failure (HF) with a multimodality assessment using several geriatric scales, showing that frailty or fragility is frequent in HF patients, even in young patients, and we demonstrated that this identified fragility played an important prognostic role. Frailty is a medical syndrome with multiple causes and contributors that increases outpatients' vulnerability so a minimal stress can cause functional impairment, with a major risk of dependency, even death. Frailty can be reversible or attenuated by interventions. Nowadays several specific scales for fragility or frailty detection are widely available. One of them, the Vulnerable Elderly Survey 13 (VES-13) has scarcely been used in HF. Purpose To assess the prevalence of fragility in an outpatient HF Clinic at first visit using both the VES-13 scale and a multimodality assessment that includes Barthel index, OARS scale, Pfeiffer test, and abbreviated Yesavage Geriatric Depression Scale of 4 items (GDS), and compare the two approaches Methods Nurses fulfilled the scales with the patients at their first visit. An scoring ≥3 in the VES-13 scale and the presence of one of the predefined criteria in the multimodality assessment (Barthel 3±1, depending on educational level; one positive depression response in abbreviated GDS; and age >85 years or nobody to turn to for help) were considered to have fragility for the purpose of the study. Results From March 2021 to December 2021, 136 patients were evaluated with the two fragility screening modalities (mean age 68.8±10.8 years, 64% men, 46% from ischaemic aetiology, 65.4%/27.9% in NYHA class II/III, LVEF 39.5% ± 13.4). VES-13 identified 51 (37.5%) patients with fragility, while the multimodality assessment detected 45 (33.6%) patients. Barthel index and depressive symptoms in the GDS were the most altered items (19 and 20 patients respectively) in the multimodality assessment. Concordance between VES-13 and multimodality assessment was 83.8%, but Cohen's Kappa was 0.65, not reaching the suitable level of 0.70. Conclusions VES-13 was capable of identifying a higher number of patients with fragility at first visit in the routine screening performed in an outpatient HF clinic, than the multimodality assessment used in the last decades. Follow-up of patients and further analysis will allow evaluating which of these two approaches adds more value for outcomes prediction. Funding Acknowledgement Type of funding sources: None.

Multiple viruses cause a phenomenon termed superinfection exclusion whereby a currently infected cell is resistant to secondary infection by the same or a closely related virus. In alphaviruses, this process is thought to be mediated, at least in part, by the viral protease (nsP2) which is responsible for processing the non-structural polyproteins (P123 and P1234) into individual proteins (nsP1-nsP4), forming the viral replication complex. Taking a synthetic-biology approach, we mimicked this naturally occurring phenomenon by generating a superinfection exclusion-like state in Aedes aegypti mosquitoes, rendering them refractory to alphavirus infection. By artificially expressing Sindbis virus (SINV) and chikungunya virus (CHIKV) nsP2 in mosquito cells and transgenic mosquitoes, we demonstrated a reduction in both SINV and CHIKV viral replication rates in cells following viral infection as well as reduced infection prevalence, viral titres and transmission potential in mosquitoes.

Substantial increases in the conjugation of the main human SUMO paralogs, SUMO1, SUMO2, and SUMO3, are observed upon exposure to different cellular stressors, and such increases are considered important to facilitate cell survival to stress. Despite their critical cellular role, little is known about how the levels of the SUMO modifiers are regulated in the cell, particularly as it relates to the changes observed upon stress. Here we characterize the contribution of alternative splicing towards regulating the expression of the main human SUMO paralogs under normalcy and three different stress conditions, heat-shock, cold-shock, and Influenza A Virus infection. Our data reveal that the normally spliced transcript variants are the predominant mature mRNAs produced from the SUMO genes and that the transcript coding for SUMO2 is by far the most abundant of all. We also provide evidence that alternatively spliced transcripts coding for protein isoforms of the prototypical SUMO proteins, which we refer to as the SUMO alphas, are also produced, and that their abundance and nuclear export are affected by stress in a stress- and cell-specific manner. Additionally, we provide evidence that the SUMO alphas are actively synthesized in the cell as their coding mRNAs are found associated with translating ribosomes. Finally, we provide evidence that the SUMO alphas are functionally different from their prototypical counterparts, with SUMO1α and SUMO2α being non-conjugatable to protein targets, SUMO3α being conjugatable but targeting a seemingly different subset of proteins from those targeted by SUMO3, and all three SUMO alphas displaying different cellular distributions from those of the prototypical SUMOs. Thus, alternative splicing appears to be an important contributor to the regulation of the expression of the SUMO proteins and the cellular functions of the SUMOylation system.

Health consequences that persist beyond the acute infection phase of COVID-19, termed post-COVID-19 condition (also commonly known as long COVID), vary widely and represent a growing global health challenge. Research on post-COVID-19 condition is expanding but, at present, no agreement exists on the health outcomes that should be measured in people living with the condition. To address this gap, we conducted an international consensus study, which included a comprehensive literature review and classification of outcomes for post-COVID-19 condition that informed a two-round online modified Delphi process followed by an online consensus meeting to finalise the core outcome set (COS). 1535 participants from 71 countries were involved, with 1148 individuals participating in both Delphi rounds. Eleven outcomes achieved consensus for inclusion in the final COS: fatigue; pain; post-exertion symptoms; work or occupational and study changes; survival; and functioning, symptoms, and conditions for each of cardiovascular, respiratory, nervous system, cognitive, mental health, and physical outcomes. Recovery was included a priori because it was a relevant outcome that was part of a previously published COS on COVID-19. The next step in this COS development exercise will be to establish the instruments that are most appropriate to measure these core outcomes. This international consensus-based COS should provide a framework for standardised assessment of adults with post-COVID-19 condition, aimed at facilitating clinical care and research worldwide.

Vitamin D may protect against breast cancer. Although Black/African American women and Hispanic/Latina women have lower circulating vitamin D levels than non-Hispanic White women, few studies have examined the association between vitamin D and breast cancer within these racial/ethnic groups.The vitamin D-breast cancer association was evaluated using a case-cohort sample of self-identified Black/African American and non-Black Hispanic/Latina women participating in the US-wide Sister Study cohort. Circulating 25-hydroxyvitamin D (25(OH)D) and 24,25-dihydroxyvitamin D (24,25(OH)2D) were measured using liquid chromatography-tandem mass spectrometry in blood samples collected at the baseline from 415 women (290 Black/African American women and 125 non-Black Hispanic/Latina women) who developed breast cancer. These were compared to concentrations in 1545 women (1084 Black/African American women and 461 Hispanic/Latina women) randomly selected from the cohort. Multivariable-adjusted Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).Over a mean follow-up of 9.2 years, women with circulating 25(OH)D concentrations above the clinical cut point for deficiency (20.0 ng/mL) had lower breast cancer rates than women with concentrations ≤ 20 ng/mL (HR, 0.79; 95% CI, 0.61-1.02). The inverse association was strongest among Hispanic/Latina women (HR, 0.52; 95% CI, 0.29-0.93), with a weaker association observed among Black/African American women (HR, 0.89; 95% CI, 0.68-1.18; P for heterogeneity = 0.13). There were no clear differences by menopausal status, follow-up time, estrogen receptor status, or invasiveness. Neither 24,25(OH)This prospective study supports the hypothesis that vitamin D may be protective against breast cancer incidence in women, including non-Black Hispanic/Latina and Black/African American women.Vitamin D may protect against breast cancer. Although women of color have lower average vitamin D levels than non-Hispanic White women, few studies have considered the role of race/ethnicity. In a sample of self-identified Black/African American and Hispanic/Latina women, we observed that vitamin D concentrations measured in blood were inversely associated with breast cancer, particularly among Latinas. These findings indicate that vitamin D may protect women against breast cancer, including those in racial/ethnic groups with low average circulating levels.

Background A substantial portion of people with COVID-19 subsequently experience lasting symptoms including fatigue, shortness of breath, and neurological complaints such as cognitive dysfunction many months after acute infection. Emerging evidence suggests that this condition, commonly referred to as long COVID but also known as post-acute sequelae of SARS-CoV-2 infection (PASC) or post-COVID-19 condition, could become a significant global health burden. Main text While the number of studies investigating the post-COVID-19 condition is increasing, there is no agreement on how this new disease should be defined and diagnosed in clinical practice and what relevant outcomes to measure. There is an urgent need to optimise and standardise outcome measures for this important patient group both for clinical services and for research and to allow comparing and pooling of data. Conclusions A Core Outcome Set for post-COVID-19 condition should be developed in the shortest time frame possible, for improvement in data quality, harmonisation, and comparability between different geographical locations. We call for a global initiative, involving all relevant partners, including, but not limited to, healthcare professionals, researchers, methodologists, patients, and caregivers. We urge coordinated actions aiming to develop a Core Outcome Set (COS) for post-COVID-19 condition in both the adult and paediatric populations.

OBJECTIVE Gestational diabetes mellitus complicates ∼6% of pregnancies and strongly predicts subsequent type 2 diabetes. It has not been fully elucidated how risk depends on the number of affected pregnancies or how long the excess risk persists. RESEARCH DESIGN AND METHODS We assessed reproductive histories in relation to risk of type 2 diabetes using a nationwide cohort of 50,884 women. Among participants who initially did not have diabetes, 3,370 were diagnosed with diabetes during 10 years of follow-up. We used Cox proportional hazards models that allowed risk to depend on age, cumulative number of pregnancies with gestational diabetes mellitus, and time since the most recent affected pregnancy, adjusting for BMI, educational level, and race/ethnicity. RESULTS History of one or more pregnancies with gestational diabetes mellitus predicted elevated age-specific risk of type 2 diabetes, with a hazard ratio of 3.87 (95% CI 2.60–5.75) 6–15 years after an affected pregnancy. Risk increased steeply with multiple affected pregnancies. The age-specific associations attenuated over time after an affected pregnancy, with an estimated 24% reduction of the hazard ratio per decade. Risk remained elevated, however, for >35 years. CONCLUSIONS Gestational diabetes mellitus predicted markedly increased rates of type 2 diabetes. Relative risk increased substantially with each additional affected pregnancy. The estimated hazard ratio declined with time after a pregnancy with gestational diabetes mellitus but remained elevated for >35 years. Women recalling a history of gestational diabetes mellitus should be screened regularly for type 2 diabetes, even late in life.

Background Vitamin D has anticarcinogenic properties, but a relationship between vitamin D supplement use and breast cancer is not established. Few studies have accounted for changes in supplement use over time or evaluated racial-ethnic differences. Methods The Sister Study is a prospective cohort of 50,884 women with 35-74 years of age who had a sister with breast cancer, but no breast cancer themselves at enrollment (2003-2009). We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between vitamin D supplement use and incident breast cancer (3,502 cases; median follow-up 10.5 years). Results Vitamin D supplement use was common, with 64% reporting ever use (at least once per month) in the year before enrollment. Considering supplement use over time, ever use of vitamin D supplements was not meaningfully associated with breast cancer (HR = 0.96, 95% CI = 0.88, 1.0), relative to never use. However, after adjusting for prior use, recent use of vitamin D supplements ≥1/month was inversely associated with breast cancer (HR = 0.88, 95% CI = 0.78, 1.0), relative to nonrecent use. The inverse association was stronger for ductal carcinoma in situ (HR = 0.67, 95% CI = 0.52, 0.87) than invasive breast cancer (HR = 0.94, 95% CI = 0.72, 1.1, p-for-heterogeneity = 0.02). Supplement use was less common among African American/Black (56%) and non-Black Hispanic/Latina (50%) women than non-Hispanic White women (66%), but there was limited evidence of racial-ethnic differences in HRs (p-for-heterogeneity = 0.16 for ever use, P = 0.55 for recent). Conclusions Our findings are consistent with the hypothesis that recent vitamin D use is inversely associated with breast cancer risk.

Aim: To develop clinical algorithms for the assessment and management of slow progress of labour. Population: Low-risk singleton, term, pregnant women in labour. Setting: Institutional births in low- and middle-income countries. Search strategy: We systematically reviewed the literature on normal labour progression, and guidance on clinical management of abnormally slow progression from 1 December 2015 to 1 October 2020 from relevant international guidelines, Cochrane reviews and primary research studies in PubMed by searching for international and national guidance documents, electronic databases and published systematic reviews using relevant keywords. Case scenarios: We developed two clinical algorithms: one for abnormally slow labour progression and arrest during first stage and one for the second stage. The algorithms provide definitions of suspected and confirmed slow progress of labour or arrest, initial assessment and ongoing monitoring, differential diagnosis, and management of the abnormalities, as well as links to other algorithms for labour management. Conclusions: Identifying abnormal progress of labour is often challenging. These algorithms may help healthcare providers identify abnormal labour progress and institute prompt management or referral where needed but also reduce misdiagnosis and unnecessary use of interventions to accelerate labour. Tweetable abstract: Evidence-based clinical algorithms may help and standardize early identification and management of abnormally slow labour progress or arrest.

People with COVID-19 might have sustained postinfection sequelae. Known by a variety of names, including long COVID or long-haul COVID, and listed in the ICD-10 classification as post-COVID-19 condition since September, 2020, this occurrence is variable in its expression and its impact. The absence of a globally standardised and agreed-upon definition hampers progress in characterisation of its epidemiology and the development of candidate treatments. In a WHO-led Delphi process, we engaged with an international panel of 265 patients, clinicians, researchers, and WHO staff to develop a consensus definition for this condition. 14 domains and 45 items were evaluated in two rounds of the Delphi process to create a final consensus definition for adults: post-COVID-19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset, with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include, but are not limited to, fatigue, shortness of breath, and cognitive dysfunction, and generally have an impact on everyday functioning. Symptoms might be new onset following initial recovery from an acute COVID-19 episode or persist from the initial illness. Symptoms might also fluctuate or relapse over time. A separate definition might be applicable for children. Although the consensus definition is likely to change as knowledge increases, this common framework provides a foundation for ongoing and future studies of epidemiology, risk factors, clinical characteristics, and therapy.

BackgroundSex disparities in acute ischemic stroke outcomes are well reported with IV thrombolysis. Despite several studies, there is still a lack of consensus on whether endovascular thrombectomy (EVT) outcomes differ between men and women.ObjectiveTo compare sex differences in EVT outcomes at 90-day follow-up and assess whether progression in functional status from discharge to 90-day follow-up differs between men and women.MethodsFrom the Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT) prospective cohort study (2016–2018), adult men and women (≥18 years) with anterior circulation large vessel occlusion (internal carotid artery, middle cerebral artery M1/M2) treated with EVT up to 24 hours from last known well were matched using propensity scores. Discharge and 90-day modified Rankin Scale (mRS) scores were compared between men and women. Furthermore, we evaluated the improvement in mRS scores from discharge to 90 days in men and women using a repeated-measures, mixed-effects regression model.ResultsOf 285 patients, 139 (48.8%) were women. Women were older with median (IQR) age 69 (57–81) years vs 64.5 (56–75), p=0.044, had smaller median perfusion deficits (Tmax >6 s) 109 vs 154 mL (pConclusionIn a propensity-matched cohort from the SELECT study, women had similar discharge outcomes as men following EVT, but the improvement from discharge to 90 days was significantly worse in women, suggesting the influence of post-discharge factors. Further exploration of this phenomenon to identify target interventions is warranted.Trial registration numberNCT02446587.

Objective: To estimate pairwise associations between administration of tocilizumab, sarilumab and usual care or placebo with 28-day mortality, in COVID-19 patients receiving concomitant corticosteroids and non-invasive or mechanical ventilation, based on all available direct and indirect evidence. Methods: Eligible trials randomized hospitalized patients with COVID-19 that compared either interleukin-6 receptor antagonist with usual care or placebo in a recent prospective meta-analysis (27 trials, 10930 patients) or that directly compared tocilizumab with sarilumab. Data were restricted to patients receiving corticosteroids and either non-invasive or invasive ventilation at randomization. Pairwise associations between tocilizumab, sarilumab and usual care or placebo for all-cause mortality 28 days after randomization were estimated using a frequentist contrast-based network meta-analysis of odds ratios (ORs), implementing multivariate fixed-effects models that assume consistency between the direct and indirect evidence. Results: One trial (REMAP-CAP) was identified that directly compared tocilizumab with sarilumab and supplied results on all-cause mortality at 28-days. This network meta-analysis was based on 898 eligible patients (278 deaths) from REMAP-CAP and 3710 eligible patients from 18 trials (1278 deaths) from the prospective meta-analysis. Summary ORs were similar for tocilizumab [0.82 [0.71-0.95, P=0.008]] and sarilumab [0.80 [0.61-1.04, P=0.09]] compared with usual care or placebo. The summary OR for 28-day mortality comparing tocilizumab with sarilumab was 1.03 [95%CI 0.81-1.32, P=0.80]. The P value for the global test for inconsistency was 0.28. Conclusion: Administration of either tocilizumab or sarilumab was associated with lower 28-day all-cause mortality compared with usual care or placebo. The association is not dependent on the choice of interleukin-6 receptor antagonist.