SORL1 Is Genetically Associated with Late-Onset Alzheimer’s Disease in Japanese, Koreans and Caucasians

To discover susceptibility genes of late-onset Alzheimer’s disease (LOAD), we conducted a 3-stage genome-wide association study (GWAS) using three populations: Japanese from the Japanese Genetic Consortium for Alzheimer Disease (JGSCAD), Koreans, and Caucasians from the Alzheimer Disease Genetic Consortium (ADGC). In Stage 1, we evaluated data for 5,877,918 genotyped and imputed SNPs in Japanese cases (n = 1,008) and controls (n = 1,016). Genome-wide significance was observed with 12 SNPs in the APOE region. Seven SNPs from other distinct regions with p-values ,261025 were genotyped in a second Japanese sample (885 cases, 985 controls), and evidence of association was confirmed for one SORL1 SNP (rs3781834, P=7.3361027 in the combined sample). Subsequent analysis combining results for several SORL1 SNPs in the Japanese, Korean (339 cases, 1,129 controls) and Caucasians (11,840 AD cases, 10,931 controls) revealed genome wide significance with rs11218343 (P=1.7761029) and rs3781834 (P=1.0461028). SNPs in previously established AD loci in Caucasians showed strong evidence of association in Japanese including rs3851179 near PICALM (P=1.7161025) and rs744373 near BIN1 (P = 1.3961024). The associated allele for each of these SNPs was the same as in Caucasians. These data demonstrate for the first time genome-wide significance of LOAD with SORL1 and confirm the role of other known loci for LOAD in Japanese. Our study highlights the importance of examining associations in multiple ethnic populations

Data from: Do failures in non-technical skills contribute to fatal medical accidents in Japan? A review of the 2010–2013 national accident reports

Objectives: We sought to clarify how large a proportion of fatal medical accidents can be considered to be caused by poor Non-Technical Skills, and to support development of a policy to reduce numbers of such accidents by making recommendations about possible training requirements. Design: Summaries of reports of fatal medical accidents, published by the Japan Medical Safety Research Organization, were reviewed individually. Three experienced clinicians and one patient safety expert conducted the reviews to determine the cause of death. Views of the patient safety expert were given additional weight in the overall determination. Setting: A total of 73 summary reports of fatal medical accidents were reviewed. These reports had been submitted by healthcare organisations across Japan to the Japan Medical Safety Research Organization between April 2010 and March 2013. Primary and secondary outcome measures: The cause of death in fatal medical accidents, categorised into technical skills, non-technical skills, and inevitable progress of disease were evaluated. Non-technical skills were further sub-divided into situation awareness, decision-making, communication, team working, leadership, managing stress, and coping with fatigue. Results: Overall, the cause of death was identified as non-technical skills in 34 cases (46.6%), disease progression in 33 cases (45.2%), and technical skills in two cases (5.5%). In two cases, no consensual determination could be achieved. Further categorisation of cases of non-technical skills were identified 14 cases (41.2%) of problems with situation awareness, eight (23.5%) with team-working, and three (8.8%) with decision-making. These three sub-categories, or combinations of them, were identified as the cause of death in 33 cases (97.1%). Conclusions: Poor non-technical skills were considered to be a significant cause of adverse events in nearly half of the fatal medical accidents examined. Improving non-technical skills may be effective for reducing accidents, and training in particular sub-categories of non-technical skills may be especially relevant

JMSRO Summary

JMSRO Summar

Effect of Mirogabalin on Chemotherapy-Induced Peripheral Neuropathy Caused by Gemcitabine plus Nab-Paclitaxel Therapy in Pancreatic Cancer Patients: A Pilot Study

Background: Gemcitabine/nab-paclitaxel therapy (GnP) is widely used to treat pancreatic cancer (PC), but chemotherapy-induced peripheral neuropathy (CIPN) is common. The CIPN is also reported to be related by microvascular damage as the basis for toxic neuropathy. However, no sufficient treatment options are available for CIPN. Mirogabalin is a novel drug for treating peripheral neuropathy. We investigated the effects of mirogabalin on CIPN due to GnP. Methods: Patients who had received GnP for PC and had taken mirogabalin for CIPN, were included. Patients completed a questionnaire about their symptoms before and after taking mirogabalin. The outcome was the change in numbness and tingling scores on the patient-reported outcomes version of the Common Terminology Criteria for Adverse Events, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Chemotherapy-Induced Peripheral Neuropathy (EORTC-QLQ-CIPN20), numerical rating scale, and adverse events (AEs). Results: Increased numbness and tingling severity (1.84 vs. 1.76; p = 0.63) and interference (1.42 vs. 1.44; p = 0.80) were not seen in any of the 25 enrolled patients. The scores on the sensory subscale of the EORTC-QLQ-CIPN improved significantly after treatment (17.5 vs. 15.7; p = 0.02). Adverse events occurred in 22 patients (88%), but there were no serious AEs (≥grade 3). Conclusions: Mirogabalin may control the progression of CIPN caused by GnP and significantly improved sensory neuropathy. However, as the incidence of AEs is high, mirogabalin should be used with caution. (UMIN:R000044039)

Role of Peroral Cholangioscopy in the Diagnosis of Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) is characterized by idiopathic biliary stricture followed by progressive cholestasis and fibrosis. When diagnosing PSC, its differentiation from other types of sclerosing cholangitis and cholangiocarcinoma is necessary. The cholangioscopic findings of PSC have not been investigated sufficiently. PSC and IgG4-related sclerosing cholangitis are difficult to distinguish by peroral cholangioscopy (POCS), but POCS is useful for excluding cholangiocarcinoma. POCS findings vary according to the condition and stage of disease. In the active phase, findings such as mucosal erythema, ulceration, fibrinous white exudate, and an irregular surface are observed and may reflect strong inflammation in the biliary epithelium. On the other hand, findings such as scarring, pseudodiverticula, and bile duct stenosis appear in the chronic phase and may reflect fibrosis and stenosis resulting from repeated inflammation. Observation of inside the bile duct by POCS might confirm the current PSC activity. Because POCS offers not only information regarding the diagnosis of PSC and PSC-associated cholangiocarcinoma but also the current statuses of biliary inflammation and stenosis, POCS could significantly contribute to the diagnosis and treatment of PSC once the characteristic findings of PSC are confirmed by future studies

Endoscopic Ultrasonography Findings of Early and Suspected Early Chronic Pancreatitis

Chronic pancreatitis (CP) is associated with a risk of pancreatic cancer and is characterized by irreversible morphological changes, fibrosis, calcification, and exocrine and endocrine insufficiency. CP is a progressive disease with a poor prognosis and is typically diagnosed at an advanced stage. The Japan Pancreas Society proposed criteria for early CP in 2009, and their usefulness has been reported. Recently, a mechanism definition was proposed by the International Consensus Guidelines and early CP was defined as a disease state that is not based on disease duration. CP is diagnosed by computed tomography, magnetic resonance imaging, and endoscopic cholangiopancreatography, which can detect calcification and dilation of the pancreatic ducts; however, detecting early CP with these modalities is difficult because subtle changes in early CP occur before established CP or end-stage CP. Endoscopic ultrasonography (EUS) is useful in the diagnosis of early CP because it allows high-resolution, close-up observation of the pancreas. In addition to imaging findings, EUS with elastography enables measurement of the stiffness of the pancreas, an objective diagnostic measure. Understanding the EUS findings of early CP is important because a histological diagnosis is problematic, and other modalities are not capable of detecting subtle changes in early CP

Best Procedure for the Management of Common Bile Duct Stones via the Papilla: Literature Review and Analysis of Procedural Efficacy and Safety

Background: Endoscopic management of common bile duct stones (CBDS) is standard; however, various techniques are performed via the papilla, and the best procedure in terms of both efficacy and safety has not been determined. Methods: Endoscopic procedures were classified into five categories according to endoscopic sphincterotomy (EST) and balloon dilation (BD): (1) EST, (2) endoscopic papillary BD (≤10 mm) (EPBD), (3) EST followed by BD (≤10 mm) (ESBD), (4) endoscopic papillary large BD (≥12 mm) (EPLBD), and (5) EST followed by large BD (≥12 mm) (ESLBD). We performed a literature review of prospective and retrospective studies to compare efficacy and adverse events (AEs). Each procedure was associated with different efficacy and AE profiles. Results: In total, 19 prospective and seven retrospective studies with a total of 3930 patients were included in this study. For EST, the complete stone removal rate at the first session, rate of mechanical lithotripsy (ML), and rate of overall AEs in EST were superior to EPBD, but a higher rate of bleeding was found for EST. Based on one retrospective study, complete stone removal rate at the first session, rate of ML, and rate of overall AEs were superior for ESBD vs. EST, and the rate of bleeding for the former was also lower. Complete stone removal rate at the first session and rate of ML for ESLBD were superior to those for EST, with no significant difference in rate of AEs. For EST vs. EPLBD, complete stone removal rate at the first session and rate of ML were superior for the latter. For EPLBD vs. ESLBD, the efficacy and safety were similar. Conclusions: ESBD is considered the best procedure for the management of small CBDS, but strong evidence is lacking. For large CBDS, both ESLBD and EPLBD are similar

Impact of the Coronavirus Disease-2019 Pandemic on Pancreaticobiliary Disease Detection and Treatment

The emergency declaration (ED) associated with the coronavirus disease-2019 (COVID-19) pandemic in Japan had a major effect on the management of gastrointestinal endoscopy. We retrospectively compared the number of pancreaticobiliary endoscopies and newly diagnosed pancreaticobiliary cancers before (1 April 2018 to 6 April 2020), during (7 April to 25 May 2020), and after the ED (26 May to 31 July). Multiple comparisons of the three groups were performed with respect to the presence or absence of symptoms and clinical disease stage. There were no significant differences among the three groups (Before/During/After the ED) in the mean number of diagnoses of pancreatic cancer and biliary cancer per month in each period (8.0/7.5/7.5 cases, p = 0.5, and 4.0/3.5/3.0 cases, p = 0.9, respectively). There were no significant differences among the three groups in the number of pancreaticobiliary endoscopies (EUS: endoscopic ultrasonography/ERCP: endoscopic retrograde cholangiopancreatography) per month (67.8/62.5/69.0 cases, p = 0.7 and 89.8/51.5/86.0 cases, p = 0.06, respectively), whereas the number of EUS cases decreased by 42.7% between before and during the ED. There were no significant differences among the three groups in the presence or absence of symptoms at diagnosis or clinical disease stage. There was no significant reduction in the newly diagnosed pancreaticobiliary cancer, even during the ED. The number of ERCP cases was not significantly reduced as a result of urgent procedures, but the number of EUS cases was significantly reduced