Immune dysregulation is characteristic of the more severe stages of SARS-CoV-2 infection. Understanding the mechanisms by which the immune system contributes to COVID-19 severity may open new avenues to treatment. Here we report that elevated interleukin-13 (IL-13) was associated with the need for mechanical ventilation in two independent patient cohorts.In addition, patients who acquired COVID-19 while prescribed Dupilumab, a mAb that blocks IL-13 and IL-4 signaling, had less severe disease. In SARS-CoV-2 infected mice, IL-13 neutralization reduced death and disease severity without affecting viral load, demonstrating an immunopathogenic role for this cytokine. Following anti-IL-13 treatment in infected mice, hyaluronan synthase 1 (Has1) was the most downregulated gene and accumulation of the hyaluronan polysaccharide was decreased in the lung. In patients with COVID-19, hyaluronan was increased in the lungs and plasma. Blockade of the hyaluronan receptor, CD44, reduced mortality in infected mice, supporting the importance of hyaluronan as a pathogenic mediator.Finally, hyaluronan was directly induced in the lungs of mice by administration of IL-13, indicating a new role for IL-13 in lung disease. Understanding the role of IL-13 and hyaluronan has important implications for therapy of COVID-19 and potentially other pulmonary diseases.Summary: IL-13 levels were elevated in patients with severe COVID-19. In a mouse model of disease, IL-13 neutralization reduced disease and decreased lung hyaluronan deposition.Administration of IL-13 induced hyaluronan in the lung. Blockade of the hyaluronan receptor CD44 prevented mortality, highlighting a novel mechanism for IL-13-mediated hyaluronan synthesis in pulmonary pathology.
Clinicaltrials.gov, NCT03028623.
Dyskinesia is a recognized but uncommon side-effect of treatment with phenytoin. Two additional cases of dyskinesia during treatment with phenytoin are described; both had radiographically documented thalamic infarctions. The reported experience to date with movement disorders induced by phenytoin is reviewed and the clinical features summarized. The available experimental evidence addressing the mechanism underlying this side effect is discussed.
Editor’s Perspective What We Know about This Topic What This Article Tells Us That Is New Background Patient perception of physician competence is important. The role of body language and physician sex on patient perceptions has not been investigated. The authors hypothesized that patients perceive anesthesiologists displaying confident body language as more competent and that patients would prefer male anesthesiologists. Methods Two hundred adult patients presenting to the Preanesthesia Evaluation and Testing Center at the University of Virginia Health System were recruited to participate using consecutive sampling. Patients viewed four 90-s videos in random order. Each video featured a male or female actor displaying confident, high-power poses or unconfident, low-power poses. Each actor recited the same script describing general anesthesia. Patients were randomized (100 per group) to view one of two sets of videos to account for any actor preferences. Participants ranked each actor anesthesiologist on perceived confidence, intelligence, and likelihood of choosing that anesthesiologist to care for their family member. Participants also chose the one actor anesthesiologist who seemed most like a leader. Results Two hundred patients watched the videos and completed the questionnaire. Actor anesthesiologists displaying confident, high-power body language had greater odds of being ranked as more confident (odds ratio, 2.27; 95% CI, 1.76 to 2.92; P < 0.0001), more intelligent (odds ratio, 1.69; 95% CI, 1.13 to 2.18; P < 0.0001), more likely chosen to care for one’s family member (odds ratio, 2.34; 95% CI, 1.82 to 3.02; P < 0.0001), and more likely to be considered a leader (odds ratio, 2.60; 95% CI, 1.86 to 3.65; P < 0.0001). Actor anesthesiologist sex was not associated with ranking for any response measures. Conclusions Patients perceive anesthesiologists displaying confident body language as more confident, more intelligent, more like a leader, and are more likely to choose that anesthesiologist to care for their family member. Differences in patient perceptions based on sex of the anesthesiologist were not detected.
Here we report on an inpatient cohort of COVID-19 positive patients where plasma cytokines were tested for association with future need for mechanical ventilation. Hierarchical clustering, Kaplan-Meier curves, and odds ratios demonstrated that two cytokines, IL-13 (OR: 1.57) and IL-7 (OR: 1.04) and the growth factor bFGF (OR: 1.04), were predictive for intubation.
Aims:The aim of the current study was to compare the prevalence of intimate partner violence (IPV) during the perinatal period among respondents with self-reported disability compared with those without a disability. Design:We conducted a secondary analysis of nationally representative data from the Pregnancy Risk Assessment Monitoring System data from 24 participating United States between 2018 and 2020. Methods:A cross-sectional sample of 43,837 respondents provided data on disability, including difficulty in vision, hearing, ambulation, cognition, communication and selfcare. The exposure was perinatal IPV, defined as experiencing abuse by a current or ex-partner in the year before or during pregnancy. Regression models were used to calculated odds of IPV by disability status while accounting for relevant sociodemographic characteristics.Results: Respondents who self-reported disabilities experienced IPV at a higher rate than those without disabilities, both before and during pregnancy. In fully adjusted models, respondents with disabilities had about 2.6 times the odds of experiencing IPV before pregnancy, and about 2.5 times the odds of experiencing IPV during pregnancy, compared with those without disabilities. Conclusion:Respondents with disabilities experienced IPV at higher rates than the general population, and thus are at increased risk for adverse maternal, neonatal and infant health outcomes.Impact: Perinatal IPV is a significant issue globally, and our findings suggest perinatal IPV is particularly salient for persons with disability. Findings highlight the need to screen women with disabilities for IPV during the perinatal period as well as the importance of providing them appropriate, accessible information, resources and referrals.
Low birth weight (LBW) is associated with a higher risk of neonatal mortality and the development of adult-onset chronic disease. Understanding the ongoing contribution of maternal hemoglobin (Hgb) levels to the incidence of LBW in South Asia is crucial to achieve the World Health Assembly global nutrition target of a 30% reduction in LBW by 2025. We enrolled pregnant women from the rural Tangail District of Bangladesh in a Maternal Newborn Health Registry established under The Global Network for Women’s and Children’s Health Research. We measured the Hgb of pregnant women at enrollment and birth weights of all infants born after 20 weeks gestation. Using logistic regression to adjust for multiple potential confounders, we estimated the association between maternal Hgb and the risk of LBW. We obtained Hgb measurements and birth weights from 1,665 mother–child dyads between July 2019 and April 2020. Using trimester-specific cutoffs for anemia, 48.3% of the women were anemic and the mean (±SD) Hgb level was 10.6 (±1.24) g/dL. We identified a U-shaped relationship where the highest risk of LBW was seen at very low (< 7.0 g/dL, OR = 2.00, 95% CI = 0.43–7.01, P = 0.31) and high (> 13.0 g/dL, OR = 2.17, 95% CI = 1.01–4.38, P = 0.036) Hgb levels. The mechanisms underlying this U-shaped association may include decreased plasma expansion during pregnancy and/or iron dysregulation resulting in placental disease. Further research is needed to explain the observed U-shaped relationship, to guide iron supplementation in pregnancy and to minimize the risk of LBW outcomes.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a unique disease, COVID-19, which ranges in severity from asymptomatic to causing severe respiratory failure and death. Viral transmission throughout the world continues at a high rate despite the development and widespread use of effective vaccines.
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