Association between Intra-Circuit Activated Clotting Time and Incidence of Bleeding Complications during Continuous Renal Replacement Therapy using Nafamostat Mesilate : a Retrospective Pilot Observational Study

It has been proposed that anticoagulant activity during continuous renal replacement therapy with nafamostat mesilate can be monitored by using intra-circuit activated clotting time. However, it is still unclear whether activated clotting time would be useful for this purpose. We conducted a retrospective study and included 76 patients who required continuous renal replacement therapy using nafamostat mesilate. We obtained information for pre- and post-filter activated clotting times and bleeding complications. We calculated time-weighted average activated clotting time. We divided the patients into three activated clotting time groups (low, middle, high) according to the tertiles of pre- and post-filter activated clotting times. Regarding post-filter time-weighted average activated clotting time, the incidence of bleeding complications in the high activated clotting time group was significantly higher than those in the low and middle activated clotting time groups (p=0.04). The incidences of bleeding complications were not significantly different among the three groups according to pre-filter time-weighted average activated clotting time (p=0.35). In sensitive analysis, the duration on continuous renal replacement therapy without bleeding complications was significantly longer for filters with post-tw ACT<262 than for those with post-tw ACT≧262 (p=0.03). This result suggested that post-filter time-weighted average activated clotting time might be a good predictor of bleeding complications during continuous renal replacement therapy with nafamostat mesilate. Further study is required to refute or confirm our findings

Malignant peripheral nerve sheath tumor arising from the greater omentum: Case report

Malignant peripheral nerve sheath tumors (MPNSTs) are rare soft tissue tumors that arise from a peripheral nerve or exhibit nerve sheath differentiation. Most of these tumors arise on the trunk, extremities, or head and neck regions; they are very rarely located in the abdominal cavity. The patient was a 71-year-old man who was referred to our hospital for a mass and pain in the right lower abdomen. Abdominal computed tomography revealed a large (9 × 9 cm), well-circumscribed, lobulated, heterogeneously enhanced mass in the pelvis. Exploratory laparotomy revealed a large mass in the greater omentum, and the tumor was completely excised. Histopathological analysis revealed that the tumor was composed of spindle cells with high mitotic activity. On staining the tumor, positive results were obtained for S-100 but negative results were obtained for c-kit, cluster of differentiation (CD)34, α-smooth muscle actin, and desmin. These findings strongly supported a diagnosis of MPNST primarily arising from the greater omentum. To the best of our knowledge, this is the first reported case of an MPNST arising from the greater omentum. In this report, we have described the case of a patient with an MPNST arising from the greater omentum and have discussed the clinical characteristics and management of MPNSTs

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

Body Mass Index as a Predictor of Postoperative Complications in Loop Ileostomy Closure after Rectal Resection in Japanese Patients

Loop ileostomy is widely employed after low rectal anastomosis to prevent pelvic sepsis from anastomotic leakage. However, stoma closure carries a risk of morbidity and even mortality in some cases. It is important to assess complications after stoma closure for maximizing the benefit of making loop ileostomy. The aim of this study was to review and examine the possible risk factors associated with complications after closure of loop ileostomies. A retrospective analysis, which focused on risk factors for complications after surgery, was performed for 82 consecutive patients who underwent elective closure of loop ileostomy from 2005-2012 at Hiroshima University Hospital. Postoperative complications developed in 22 patients (26.8%): 12 (14.6%) had an ileus, 8 (9.8%) had a wound infection, 2 (2.4%) had an intraperitoneal abscess and 1 had pseudomembranous enterocolitis. There was no postoperative mortality. In univariate analysis, gender and higher body mass index (BMI) were identified as significant risk factors for postoperative complications. After multivariate analysis, a BMI of 24 kg/m2 was identified as the cut-off value, above which significantly higher incidences of postoperative complications were observed. Furthermore, patients who succeeded in reducing their weight (BMI 24 kg/m2). Our study showed that the majority of complications associated with ileostomy closure are ileus. A BMI >24 kg/m2 is an independent risk factor for postoperative complications. Weight loss programs before stoma closure might reduce postoperative complications

Submucosal Invasive Micropapillary Carcinoma of the Colon with Massive Lymph Node Metastases: A Case Report

Micropapillary carcinoma was originally reported to be an aggressive variant of breast carcinoma, and it is associated with frequent lymphovascular invasion and a dismal clinical outcome. It has subsequently been found in other organs; however, at present, only a limited number of cases of colorectal micropapillary carcinoma have been reported. We present a case of early colon cancer with extensive nodal metastases in a Japanese patient. An 82-year-old man was found by colonoscopy to have a 20-mm pedunculated polyp in his sigmoid colon. Endoscopic resection of the sigmoid colon tumor was performed, and pathological examination of the resected specimen revealed a poorly differentiated adenocarcinoma component and a micropapillary component. Despite the tumor being confined within the submucosa, massive lymphatic invasion was noted. Thereafter, the patient underwent laparoscopic sigmoidectomy with lymph node dissection, and multiple lymph node metastases were observed. Our case suggests that when a micropapillary component is identified in a pre-operative biopsy specimen, even for early colorectal cancer, surgical resection with adequate lymph node dissection would be required because of the high potential for nodal metastases