Patient self-reported symptoms using visual analog scales are useful to estimate endoscopic activity in ulcerative colitis

Background/Aims In clinical practice, colonoscopy has been regarded as the gold standard for the evaluation of disease severity as well as mucosal healing in ulcerative colitis (UC). Some activity indices incorporating patient symptoms as parameters have been shown to reflect the endoscopic activity of UC. The aim of this study was to examine whether self-reported symptoms with visual analog scales (VAS) can predict endoscopic activity. Methods A cross-sectional study of 150 UC patients who underwent colonoscopy with submission of VAS scores of 4 symptoms: general condition, bloody stools, stool form, and abdominal pain (0: no symptoms, 10: the most severe symptoms). Each VAS score was compared with colonoscopic activity assessed with the Mayo endoscopic subscore (MES). Results All VAS scores were significantly correlated with the endoscopic severity (Spearman correlation coefficients of general condition, bloody stools, stool form, and abdominal pain: 0.63, 0.64, 0.58, and 0.43, respectively). Mucosal healing defined as MES 0 alone was predicted by VAS score <1.5 on general condition or 0 on bloody stools with sensitivity of 0.84 and 0.76 and specificity of 0.66 and 0.76, respectively. Additionally, VAS score <2.5 on stool form predicted active lesions in distal colorectum alone with sensitivity of 0.67 and specificity of 0.66, suggesting that this item could predict the indication of topical therapy. Conclusions Self-reported VAS scores on symptoms were correlated with endoscopic activity of UC. To clarify the relationship between VAS and mucosal healing, further validation studies are needed

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

Up-regulation of Gr1 + CD11b + cell population in the spleen of NaClO-administered mice works to repair skin wounds

In wound healing, early infiltration of neutrophils followed by macrophage infiltration are important defense mechanisms for repair of tissue damage.　Here we examined the effects of neutrophils on wound healing. Administration of sodium hypochlorite (NaClO) to mouse skin induces neutrophil recruitment to the wound site and repeated administration of NaClO was shown to prolong wound healing. Examination of the spleens of mice whose wounds were repeatedly treated with NaClO, showed that GR-1&lt;sup&gt;+&lt;/sup&gt;CD11b&lt;sup&gt;+&lt;/sup&gt; cells were up regulated in the recovery phase of wounding. Many of the GR-1&lt;sup&gt;+&lt;/sup&gt;CD11b &lt;sup&gt;+&lt;/sup&gt; cells in the mouse bone marrow were neutrophils, as indicated by a ring-shaped nucleus, and some of the cells were immature myeloid-lineage cells. GR-1&lt;sup&gt;+&lt;/sup&gt;CD11b&lt;sup&gt;+&lt;/sup&gt; cells from bone marrow were sorted and injected intravenously to syngeneic Imprinting Control Region (ICR) mice. The mice that received GR-1&lt;sup&gt;+&lt;/sup&gt;CD11b&lt;sup&gt;+&lt;/sup&gt; cells recovered faster than the mice injected with the control, phosphate buffer saline (PBS)