Association of airway obstruction with first-pass success and intubation-related adverse events in the emergency department: multicenter prospective observational studies

BackgroundAirway obstruction is a relatively rare but critical condition that requires urgent intervention in the emergency department (ED). The present study aimed to investigate the association of airway obstruction with first-pass success and intubation-related adverse events in the ED.MethodsWe analyzed data from two prospective multicenter observational studies of ED airway management. We included adults (aged ≥18 years) who underwent tracheal intubation for non-trauma indications from 2012 through 2021 (113-month period). Outcome measures were first-pass success and intubation-related adverse events. We constructed a multivariable logistic regression model adjusting for age, sex, modified LEMON score (without airway obstruction), intubation methods, intubation devices, bougie use, intubator’s specialty, and ED visit year with accounting for patients clustering within the ED.ResultsOf 7,349 eligible patients, 272 (4%) underwent tracheal intubation for airway obstruction. Overall, 74% of patients had first-pass success and 16% had intubation-related adverse events. The airway obstruction group had a lower first-pass success rate (63% vs. 74%; unadjusted odds ratio [OR], 0.63; 95% CI, 0.49–0.80), compared to the non-airway obstruction group. This association remained significant in the multivariable analysis (adjusted OR 0.60, 95%CI 0.46–0.80). The airway obstruction group also had a significantly higher risk of adverse events (28% vs. 16%; unadjusted OR, 1.93; 95% CI, 1.48–2.56, adjusted OR, 1.70; 95% CI, 1.27–2.29). In the sensitivity analysis using multiple imputation, the results remained consistent with the main results: the airway obstruction group had a significantly lower first-pass success rate (adjusted OR, 0.60; 95% CI, 0.48–0.76).ConclusionBased on these multicenter prospective data, airway obstruction was associated with a significantly lower first-pass success rate and a higher intubation-related adverse event rate in the ED

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Solid acid-catalyzed one-step synthesis of oleacein from oleuropein

Abstract In this study, we developed a new synthetic strategy to convert secoiridoid glucosides into unique dialdehydic compounds using solid acid catalysts. Specifically, we succeeded in the direct synthesis of oleacein, a rare component of extra-virgin olive oil, from oleuropein, which is abundant in olive leaves. Whereas the conventional total synthesis of oleacein from lyxose requires more than 10 steps, these solid acid catalysts enabled the one-step synthesis of oleacein from oleuropein. A key step in this synthesis was the selective hydrolysis of methyl ester. Density functional theory calculations at the B3LYP/631+G (d) level of theory revealed the formation of a tetrahedral intermediate bonded to one H2O molecule. These solid acid catalysts were easily recovered and reused at least five times by simple cleaning. Importantly, this synthetic procedure was not only applicable to other secoiridoid glucosides, but could also be employed for the corresponding scale-up reaction using oleuropein extracted from olive leaves as the starting material

Development of a toileting performance assessment test for patients in the early stroke phase

<p><b>Purpose:</b> The study aimed to develop a toileting performance assessment test to measure the toileting performance ability of patients in the early phase after stroke.</p> <p><b>Methods:</b> In this study, 214 stroke patients were enrolled. Cronbach’s <i>α</i>, Spearman’s rank correlations (<i>ρ</i> values) with the toileting-related items of the functional independence measure and Barthel Index, interrater reliability (weighted <i>κ</i>), and responsiveness (standardized response mean) were evaluated. Receiver operating characteristic and the area under the curves were utilized to determine the cutoff scores for the significance of the independence of toilet ability with the functional independence measure and Barthel Index.</p> <p><b>Results:</b> Cronbach’s <i>α</i> was ≥0.90. The <i>p</i> values between toileting performance assessment test and Barthel Index and between toileting performance assessment test and functional independence measure were 0.88 and 0.86, respectively. The weighted <i>κ</i> for each item was ≥0.61. The standardized response means were 0.81 for the functional independence measure, 0.70 for the Barthel Index, and 0.93 for the toileting performance assessment test. Cutoff scores of the toileting performance assessment test were 18 points.</p> <p><b>Conclusions:</b> The toileting performance assessment test has acceptable psychometric properties and proved useful in assessing toileting performance ability of patients in the early phase after stroke.Implications for rehabilitation</p><p>Toileting performance assessment test demonstrated acceptable psychometric properties, and it can be useful for assessing the toileting ability of patients in the early phase after stroke.</p><p>Toileting performance assessment test should provide information that leads to lowered risk of falls while toileting, and the information gathered can assist patients in achieving early toileting independence after stroke.</p><p>As the development of toileting performance assessment test excluded patients with cognitive disabilities, the item for cognitive function should be developed as well.</p><p></p> <p>Toileting performance assessment test demonstrated acceptable psychometric properties, and it can be useful for assessing the toileting ability of patients in the early phase after stroke.</p> <p>Toileting performance assessment test should provide information that leads to lowered risk of falls while toileting, and the information gathered can assist patients in achieving early toileting independence after stroke.</p> <p>As the development of toileting performance assessment test excluded patients with cognitive disabilities, the item for cognitive function should be developed as well.</p