Conventional versus Rapid Glucocorticoid Tapering in Severe Systemic Lupus Erythematosus Patients: A Non-Blind, Randomized Controlled Trial

Glucocorticoids (GCs) have long played a central role in the treatment of systemic lupus erythematosus (SLE), but these drugs have many adverse effects. We will determine whether rapid weekly GC tapering is non-inferior to conventional biweekly tapering in patients with severe SLE. This is a randomized, open-label, multicenter controlled trial. The primary outcome is the relapse-free survival rate at 52 weeks. The main secondary outcome is the prevalence of the Lupus Low Disease Activity State at 52 weeks. The trial will determine the optimal method of tapering GCs in patients with severe SLE

Conventional-dose Versus Half-dose Sulfamethoxazole-trimethoprim for the Prophylaxis of Pneumocystis Pneumonia in Patients with Systemic Rheumatic Disease: A Non-blind, Randomized Controlled Trial

Pneumocystis pneumonia (PCP) due to Pneumocystis jirovecii infection is the leading cause of fatal opportunistic infections in immunocompromised patients. We will determine whether a daily sulfamethoxazole-trimethoprim (SMX/TMP) dose of 200/40 mg was non-inferior to 400/80 mg for PCP prevention in patients with systemic rheumatic disease under immunosuppressive therapy. This is a randomized, open-label, multicenter controlled trial. The primary outcome is the rate of PCP prevention at 52 weeks. The secondary outcome is the discontinuation rate of SMX/TMP. The trial will evaluate the optimal dose of SMX/TMP for PCP prevention in patients with systemic rheumatic disease under immunosuppressive therapy

心臓血管外科領域におけるゼラチンシートの止血効果、癒着防止効果の検討

BACKGROUND:The bi1ayer gelatin sealing sheet was developed as a safe, effective, easy-to-handle and low-cost hemostatic agent. OBJECTIVE:To examine the feasibility of gelatin sealing sheets using a canine aterial hemorrhage mode1. METHODS:In vivo degradation of gelatin sealing sheets was examined by implanting subcutaneously in rats. For the hemostatic and anti-adhesion efficacy investigations, femoral arteries of dogs were pricked with syringe needle to make as mall hole, and a gelatin(i.e. experimental group) or fibrin glue sealing sheet (i.e. control group) was applied on the hole to stop bleeding (n=8). After discontinuation of the bleeding, the skin incisions were closed and re-examined 4 weeks postoperatively. RESULTS:From the degradation study, 4h thermally treated gelatin sheet which degraded within 3 weeks in vivo was chosen for the further hemostatic study. In all cases of gelatin and fibrin glue sealing sheets, bleeding from the needle hole on canine femoral arteries was effectively stopped. Postoperative adhesions and inflammation at the site in the experimental group were significantly less than those in the control group (P<0.01 for adhesion scores). CONCLUSIONS:The gelatin sealing sheet was found to be as effective as the fibrin glue sealing sheet as a surgical hemostatic agent, and more effective in preventing postoperative adhesions.博士（医学）・甲第632号・平成27年3月16日Copyright ©2015 IOS Pres

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