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Summary Background Autochthonous (locally acquired) hepatitis E is increasingly recognised in developed countries, and is thought to be a porcine zoonosis. A range of extra‐hepatic manifestations of hepatitis E infection have been described, but have never been systematically studied. Aim To report the extra‐hepatic manifestations of hepatitis E virus. Methods Retrospective review of data of 106 cases of autochthonous hepatitis E (acute n = 105, chronic n = 1). Results Eight (7.5%) cases presented with neurological syndromes, which included brachial neuritis, Guillain‐Barré syndrome, peripheral neuropathy, neuromyopathy and vestibular neuritis. Patients with neurological syndromes were younger (median age 40 years, range 34–92 years, P = 0.048) and had a more modest transaminitis (median ALT 471 IU/L, P = 0.015) compared to cases without neurological symptoms [median age 64 years (range 18–88 years), median ALT 1135 IU/L]. One patient presented with a cardiac arrhythmia,twelve patients (11.3%) presented with thrombocytopenia, fourteen (13.2%) with lymphocytosis and eight (7.5%) with a lymphopenia, none of which had any clinical consequence. Serum electrophoresis was performed in 65 patients at presentation, of whom 17 (26%) had a monoclonal gammopathy of uncertain significance. Two cases developed haematological malignancies, acute myeloid leukaemia and duodenal plasmacytoma, 18 and 36 months after presenting with acute hepatitis E infection. Conclusions A range of extra‐hepatic manifestations can occur with hepatitis E. Neurological and haematological features of hepatitis E infection are relatively frequent in this UK cohort, and result in significant morbidity which warrants further study.

BackgroundVasoactive medications are essential in septic shock, but are not fully incorporated into current mortality prediction risk scores. We sought to develop a novel mortality prediction model for septic shock incorporating quantitative vasoactive medication usage.MethodsQuantitative vasopressor use was calculated in a cohort of 5352 septic shock patients and compared using norepinephrine equivalents (NEE), cumulative vasopressor index and the vasoactive inotrope score models. Having best discrimination prediction, log10NEE was selected for further development of a novel prediction model for 28-day and 1-year mortality via backward stepwise logistic regression. This model termed ‘MAVIC’ (Mechanical ventilation, Acute Physiology And Chronic Health Evaluation-III, Vasopressors, Inotropes, Charlson comorbidity index) was then compared to Acute Physiology And Chronic Health Evaluation-III (APACHE-III) and Sequential Organ Failure Assessment (SOFA) scores in an independent validation cohort for its accuracy in predicting 28-day and 1-year mortality.Measurements and main resultsThe MAVIC model was superior to the APACHE-III and SOFA scores in its ability to predict 28-day mortality (area under receiver operating characteristic curve [AUROC] 0.73 vs. 0.66 and 0.60) and 1-year mortality (AUROC 0.74 vs. 0.66 and 0.60), respectively.ConclusionsThe incorporation of quantitative vasopressor usage into a novel ‘MAVIC’ model results in superior 28-day and 1-year mortality risk prediction in a large cohort of patients with septic shock.

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Background Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX). Methods In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.

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Background: Gestational diabetes mellitus (GDM) is a glucose tolerance disorder that occurs or is diagnosed for the first time during pregnancy. Perinatal morbidity is more and women with GDM have more risk of developing diabetes. Uttar Pradesh is a state of India with one of the highest rate of infant as well as maternal mortality which might be, at least partially, due to GDM. Thus, appropriate assessment and management of GDM can improve the outcomes. Aims & Objectives: Primary objective of this study was to determine the prevalence of GDM and evaluate the maternal and fetal outcome in and around Kanpur. Thus, this study was undertaken to know the extent of burden on the healthcare, before scope of intervention could be defined. Materials and Methods: A prospective study (September, 2012-October, 2014) was done at 198 healthcare facilities. 24,656 mothers were screened (24 th-28 th weeks of pregnancy) as per guidelines of Diabetes in Pregnancy Study Group India (DIPSI) and Federation of Obstetric and Gynecological Societies of India (FOGSI). Results: > 94% pregnant women did not know about GDM. Prevalence of GDM was 14.42%. Stillbirth, Perinatal & neonatal mortality were respectively 2, 3.3 & 6 times higher in GDM. Most of the GDM were diagnosed in primigravida (62%). Congenital Malformation was 8 times higher. Low Birth Weight (LBW) was 35% in GDM (16% in Non GDM). GDM positive cases had 20.6% positive family history of diabetes (compared to 6.5% in non-GDM). Relative risks for PBU (post birth unit), LGA (large for gestational age), LBW (low birth weight), pre-eclampsia and jaundice were also higher. Conclusion: A well predictive screening criteria is needed. As the ignorance about GDM among pregnant ladies is high, to reduce the risk, awareness can be an area of thrust.

Morbidly obese patients had lower in-hospital mortality but had higher 1-year mortality compared to normal weight and underweight patients. Cumulative norepinephrine exposure was highest in morbidly obese patients. Total norepinephrine exposure was an independent mortality predictor in septic shock.