Clinical Diversity in Biliary Pancreatitis — Classification of Two Types

One hundred and seven patients with biliary pancreatitis undergoing operation from 1976 to 1989 were reviewed. To clarify the reason for failure to respond to conventional supportive therapy, 73 patients (68%) who underwent emergency surgery were retrospectively divided into two groups according to the severity of the pancreatitis evaluated at laparotomy and compared. Sixty-two had minimal or mild pancreatitis (Group I), among whom 44 (71%) had life-threatening acute biliary tract disease. All underwent biliary surgery and 4 (6%) subsequently died, 2 due to acute obstructive suppurative cholangitis. Eleven had hemorrhagic necrotizing pancreatitis (Group II), among whom 7 had complications of acute pancreatitis such as pancreatic ascites or abscess. These underwent pancreatic and/or biliary surgery and 3 (27%) died of multi-organ failure

Etiology and Pathogenesis of Marked Elevation of Serum Transaminase in Patients With Acute Gallstone Disease

From 1980 through 1988, biliary surgery was performed in 197 patients with acute gallstone disease and concomitant elevation of serum glutamic oxalacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) of over 300 Karmen units. In 137 patients, anatomic inspection and liver biopsy were performed during the acute stage of the disease. Impacted and floating bile duct stones were found in 69 (50%) and in 43 (32%) of the 137 patients, respectively. The main liver histology was necrosis of liver cells. After surgery, high serum transaminase fell rapidly with immediate recovery in 99% of the patients. In the remaining 60 patients, their signs and symptoms settled soon after initial conservative treatment and surgery was performed after an average time of 21 days. At laparotomy, impacted bile duct stones were found in 2 (3%) and liver histology revealed regeneration of liver cells

Duodenal ulcer penetration into the superior mesenteric artery after percutaneous transluminal angioplasty and stent placement for acute mesenteric ischemia: report of a case

A 78-year-old male presented with the chief complaints of abdominal pain and vomiting. Contrast-enhanced computed tomography and abdominal angiography showed occlusion of the superior mesenteric artery due to thrombosis, and emergency percutaneous transluminal angioplasty and stent placement were carried out. Two months later, stent thrombosis developed, and a second stent was placed. Eight months later, he complained of general fatigue and anorexia. Gastrointestinal endoscopy revealed a duodenal ulcer at the third portion close to the superior mesenteric artery. Thirteen days after conservative management, duodenal ulcer penetration into the superior mesenteric artery with subsequent air embolism developed, and the patient died of multiple organ failure

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