Efficacy of Mucosal Cutting Biopsy for the Histopathological Diagnosis of Gastric Submucosal Tumors

Background: Gastrointestinal stromal tumors occur frequently. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is performed commonly for diagnosis. However, the success rate of histological diagnosis is insufficient when the submucosal tumor (SMT) is small. Recently, another technique, mucosal cutting biopsy (MCB) has been reported. The aim of this study is to evaluate the efficacy and safety of MCB. Method: Between January 2012 and August 2018, MCB and EUS-FNA were performed 16 and 31 times for diagnosing gastric SMT. The diagnostic rate, the rate of successful immunohistochemistry, and the safety were reviewed. Difficult locations for EUS-FNA were also evaluated. Results: The mean SMT sizes measured on MCB and EUS-FNA were 21.2 and 36.2 mm. The diagnostic rates of MCB and EUS-FNA were almost the same (88 vs. 81%), but successful immunohistochemistry was significantly higher in the MCB group (93 vs. 59%, p = 0.03). In the subgroup of SMTs < 20 mm, the successful histological diagnosis rate from EUS-FNA was relatively low. There were no complications. Failures of EUS-FNA were more frequent in the middle third of the stomach. Conclusions: MCB was an effective procedure for diagnosing gastric SMT, especially in the case of small SMTs located at the middle third of the stomach

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

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

Efficacy and safety of scheduled early endoscopic ultrasonography‐guided ethanol reinjection for patients with pancreatic neuroendocrine tumors: Prospective pilot study

Endoscopic ultrasonography (EUS)‐guided ethanol injection was recently proposed for treatment of patients with small pancreatic neuroendocrine tumors (p‐NET); however, tips on how to carry out safe and effective procedures are unclear. We launched a pilot study for scheduled early EUS‐guided ethanol reinjection for small p‐NET. Major eligibility criteria were presence of pathologically diagnosed grade (G) 1 or G2, tumor size ≤2 cm and being a poor or rejected candidate for surgery. For the treatment, we used a 25‐gauge needle and pure ethanol. Contrast‐enhanced computed tomography (CE‐CT) was carried out on postoperative day 3, and if enhanced areas of the tumor were still apparent, an additional session was scheduled during the same hospitalization period. Primary endpoint was complete ablation rate at 1 month after treatment, and secondary endpoint was procedure‐related adverse events. A total of five patients were treated. Median size of the tumor was 10 (range: 7–14) mm. Of the five patients, three underwent an additional session. Median volume of ethanol injection per session was 0.8 (range: 0.3–1.0) mL, and the total was 1.0 (0.9–1.8) mL. Complete ablation was achieved in four of the five tumors (80%) with no adverse events. During 1 year of follow up, none of the patients reported any procedure‐related adverse events, and no recurrence of tumor. Scheduled early EUS‐guided ethanol reinjection appears to be safe and effective for treating small p‐NET (UMIN number: 000018834)

Appendix A. Microfocus X-ray Computed Tomography cross-sectional images of Joergensenium arcticum Ikenoue, Dumitrica and Bjørklund n. sp.

Radiolarians in the Arctic Ocean have been studied lately in both plankton and sediment trap samples in the Chukchi Sea area. These studies have shed light on new radiolarian taxa, especially within the order Entactinaria, including two new species of Joergensenium, Joergensenium arcticum from the western Arctic Ocean, so far restricted to the Pacific Winter Water in the Chukchi Sea, and Joergensenium clevei hitherto found in the northern part of the Norwegian Sea south of the Fram Strait. The taxonomic position of the order Entactinaria is discussed and the genus Joergensenium has been emended. We have also observed in detail the internal structure of J. arcticum using Microfocus X-ray Computed Tomography and have utilized three-dimensional imaging for the first time in a species description