Boerhavia diffusa attenuates podocyte injury in rats with adenine induced chronic kidney disease by enhancing nephrin expression.

Nephrin is a transmembrane protein that maintains the slit diaphragm of renal podocyte. In chronic kidney disease (CKD), podocyte effacement causes damage to glomerular basement membrane barrier leading to proteinuria. Boerhavia diffusa, (BD), an Ayurveda herb, is used in treatment of various diseases particularly in relation to the urinary system. This study attempts to evaluate the effect of ethanolic extract of BD on the expression of nephrin in adenine induced CKD rats. CKD was induced in Wistar albino rats using adenine (600/mg/kg, orally for 10 days). CKD rats were treated with BD (400/mg/kg) and pirfenidone (500/mg/kg) orally for 14 days. The kidneys were harvested from euthanized animals and processed for histopathology, electron microscopy and immunohistochemistry, gene and protein expression of nephrin. Diseased rats treated with BD and pirfenidone showed reduction in the thickening of renal basement membranes and reduced haziness in brush border of PCT and glomeruli. Nephrin gene and protein expressions were higher in BD and pirfenidone treated group when compared to the disease control group. The structural and functional damage brought on by adenine-induced nephrotoxicity was countered by protective action of BD by up regulating the expression of nephrin. Therefore, BD can be utilized as a nutraceutical for the prevention and treatment of CKD.

Prolonged T-cell activation and long COVID symptoms independently associate with severe COVID-19 at 3 months.

Coronavirus disease-19 (COVID-19) causes immune perturbations which may persist long term, and patients frequently report ongoing symptoms for months after recovery. We assessed immune activation at 3-12 months post hospital admission in 187 samples from 63 patients with mild, moderate, or severe disease and investigated whether it associates with long COVID. At 3 months, patients with severe disease displayed persistent activation of CD4+ and CD8+ T-cells, based on expression of HLA-DR, CD38, Ki67, and granzyme B, and elevated plasma levels of interleukin-4 (IL-4), IL-7, IL-17, and tumor necrosis factor-alpha (TNF-α) compared to mild and/or moderate patients. Plasma from severe patients at 3 months caused T-cells from healthy donors to upregulate IL-15Rα, suggesting that plasma factors in severe patients may increase T-cell responsiveness to IL-15-driven bystander activation. Patients with severe disease reported a higher number of long COVID symptoms which did not however correlate with cellular immune activation/pro-inflammatory cytokines after adjusting for age, sex, and disease severity. Our data suggests that long COVID and persistent immune activation may correlate independently with severe disease.

Clinical characteristics and outcomes of 85 intensive care patients with Covid-19 in South London: A single centre observational study.

Background: In March 2020, Covid-19 secondary to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was declared a global pandemic. Methods: This retrospective observational study included patients with Covid-19, managed in a single intensive care unit (ICU). We collected data on patient characteristics, laboratory and radiological findings and ICU management. Data are reported as median (interquartile range). Binary logistic regression modelling was used to identify variables at ICU admission associated with mortality. Results: 85 patients (age 57.3 years [49.4-64.2], 75.3% male) were followed up for 34 days (26-40). The commonest comorbidities were hypertension (51.8%), obesity (48.7%), and type 2 diabetes (31.8%). Covid-19 presented with shortness of breath (89.4%), fever (82.4%), and cough (81.2%), first noted 8 days (6-10) prior to ICU admission. PaO2/FiO2-ratios at ICU admission were 8.28 kPa (7.04-11.7). Bilateral infiltrates on chest X-ray, lymphopenia, and raised C-reactive protein and ferritin were typical. 81.2% received invasive mechanical ventilation (IMV). Acute kidney injury occurred in 62.4% with renal replacement therapy required in 20.0%. By the end of the follow-up period, 44.7% had died, 30.6% had been discharged from hospital, 14.1% had been discharged from ICU but remained in hospital and 10.6% remained in ICU. ICU length of stay was 14 days (9-23). Age was the only variable at admission which was associated with mortality. PaO2/FiO2-ratio, driving pressure and peak ferritin and neutrophil count over the first 72-hours of IMV all correlated with mortality. Conclusions: We report the clinical characteristics, ICU practices and outcomes of a South London cohort with Covid-19, and have identified factors which correlate with mortality. By sharing our insight, we hope to further understanding of this novel disease.

Subcutaneous Emphysema, Pneumomediastinum, and Pneumothorax in Critically Ill Patients With Coronavirus Disease 2019: A Retrospective Cohort Study.

IMPORTANCE: Management of severe coronavirus disease 2019 relies on advanced respiratory support modalities including invasive mechanical ventilation, continuous positive airway pressure, and noninvasive ventilation, all of which are associated with the development of subcutaneous emphysema, pneumomediastinum, and pneumothorax (herein collectively termed barotrauma). OBJECTIVES: To assess the occurrence rate of barotrauma in severe coronavirus disease 2019 and to explore possible associated factors. DESIGN SETTING AND PARTICIPANTS: A retrospective, single-center cohort study with nested case series, conducted at University Hospital Lewisham: a 450-bed general hospital in London, United Kingdom. All patients with confirmed coronavirus disease 2019 admitted to the critical care department from March 12, to April 12, 2020, were included. MAIN OUTCOMES AND MEASURES: Patients were retrospectively screened for radiological evidence of barotrauma. Admission characteristics, modalities of respiratory support, and outcomes were compared between barotrauma and nonbarotrauma groups. Respiratory parameters in the period preceding barotrauma identification were recorded. RESULTS: Of 83 admissions with coronavirus disease 2019, eight suffered barotrauma (occurrence rate 9.6%; 95% CI 4.3%-18.1%). Barotrauma cases had longer illness duration prior to critical care admission (10 vs 7 d; interquartile range, 8-14 and 6-10, respectively; p = 0.073) and were more often treated with continuous positive airway pressure or noninvasive ventilation as the initial modality of advanced respiratory support (87.5% vs 36.0%; p = 0.007). Patients managed with continuous positive airway pressure or noninvasive ventilation prior to the development of barotrauma had median minute ventilation of 16.2-19.9 and 21.3-22.7 L/min, respectively. Compared with the nonbarotrauma group, a higher proportion of patients with barotrauma had died (62.5% vs 43.2%), and a lower proportion of patients had been discharged (25.0% vs 53.3%) at 3-month follow-up. CONCLUSIONS AND RELEVANCE: Barotrauma appears to be a common complication of severe coronavirus disease 2019. Determining whether high minute ventilation while using continuous positive airway pressure or noninvasive ventilation predisposes patients to barotrauma requires further investigation.

Outcomes following severe hand foot and mouth disease: A systematic review and meta-analysis.

BACKGROUND: Hand, foot and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) is associated with acute neurological disease in children. This study aimed to estimate the burden of long-term sequelae and death following severe HFMD. METHODS: This systematic review and meta-analysis pooled all reports from English and Chinese databases including MEDLINE and Wangfang on outbreaks of clinically diagnosed HFMD and/or laboratory-confirmed EV-A71 with at least 7 days' follow-up published between 1st January 1966 and 19th October 2015. Two independent reviewers assessed the literature. We used a random effects meta-analysis to estimate cumulative incidence of neurological sequelae or death. Studies were assessed for methodological and reporting quality. PROSPERO registration number: 10.15124/CRD42015021981. FINDINGS: 43 studies were included in the review, and 599 children from 9 studies were included in the primary analysis. Estimated cumulative incidence of death or neurological sequelae at maximum follow up was 19.8% (95% CI:10.2%, 31.3%). Heterogeneity (Iˆ2) was 88.57%, partly accounted for by year of data collection and reporting quality of studies. Incidence by acute disease severity was 0.00% (0.00, 0.00) for grade IIa; 17.0% (7.9, 28.2) for grade IIb/III; 81.6% (65.1, 94.5) for grade IV (p = 0.00) disease. CONCLUSIONS: HFMD with neurological involvement is associated with a substantial burden of long-term neurological sequelae. Grade of acute disease severity was a strong predictor of outcome. Strengths of this study include its bilingual approach and clinical applicability. Future prospective and interventional studies must use rigorous methodology to assess long-term outcomes in survivors. FUNDING: There was no specific funding for this study. See below for researcher funding.