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Background: Due to the global increase in alcoholic liver disease (ALD) rates, interest in gut-derived bacterial products is growing in targeted therapies. Identifying microbiome-derived metabolite signatures is challenging due to the complex patterns that have long-term effects on the development of ALD. We evaluated a feature of the gut-microbiota-derived metabolite signatures in patients with ALD. Methods: A prospective cohort study was carried out between April 2017 and March 2022. Stool samples (healthy control [HC, n = 62], alcoholic fatty liver [AFL, n = 25], alcoholic hepatitis [AH, n = 80], and alcoholic cirrhosis [AC, n = 80]) were collected for the microbiota analysis by 16S rRNA sequencing and metabolite profiles by using GC-MS and LC-MS methods. Results: Proteobacteria relative abundance increased in ALD, while Bacteroides decreased (p = 0.001). Fusobacteria levels were found to be higher in AH (p = 0.0001). A total of 103 metabolites were quantified and screened. 3-Indole propionic acid levels are significantly lower in AH and AC (p = 0.001). Surprisingly, AC increases indole-3-lactic acid (p = 0.04). AC had significantly lower levels of short-chain fatty acids (SCFAs) and bile acids (BAs). The levels of stercobilin, hexadecanedioic acid, and 3-methyladipic acid were significantly decreased in ALD. The pathways of linoleic acid metabolism, indole compounds, histidine metabolism, fatty acid degradation, and glutamate metabolism were closely related to ALD metabolism. Conclusions: Short-chain fatty acids, bile acids, and indole metabolites were depleted according to the ALD progression. Microbial dysbiosis is associated with a shift in metabolite changes in ALD. Clinicaltrials.gov, number NCT04339725.

The coronavirus disease 2019 (COVID-19) pandemic has reduced the ability to prevent or control chronic disease due to the concerns about safety in accessing health care. Inflammatory bowel disease (IBD) is a chronic condition requiring long- term sustained treatment, which is difficult in the current panedemic situation. The Korean Association for the Study of Intestinal Diseases (KASID) has developed an expert consensus statement on the clinical practice management of adult inflammatory bowel disease during the COVID-19 pandemic. This expert consensus statement is based on guidelines and clinical reports from several countries around the world. It provides recommendations to deal with the risk of COVID-19 and medication use in IBD patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and emphasizes the importance of right treatment approach to avoid worsening of the disease condition in IBD patients.

Background: Establishment of an artificial intelligence model in gastrointestinal endoscopy has no standardized dataset. The optimal volume or class distribution of training datasets has not been evaluated. An artificial intelligence model was previously created by the authors to classify endoscopic images of colorectal polyps into four categories, including advanced colorectal cancer, early cancers/high-grade dysplasia, tubular adenoma, and nonneoplasm. The aim of this study was to evaluate the impact of the volume and distribution of training dataset classes in the development of deep-learning models for colorectal polyp histopathology prediction from endoscopic images. Methods: The same 3828 endoscopic images that were used to create earlier models were used. An additional 6838 images were used to find the optimal volume and class distribution for a deep-learning model. Various amounts of data volume and class distributions were tried to establish deep-learning models. The training of deep-learning models uniformly used no-code platform Neuro-T. Accuracy was the primary outcome on four-class prediction. Results: The highest internal-test classification accuracy in the original dataset, doubled dataset, and tripled dataset was commonly shown by doubling the proportion of data for fewer categories (2:2:1:1 for advanced colorectal cancer: early cancers/high-grade dysplasia: tubular adenoma: non-neoplasm). Doubling the proportion of data for fewer categories in the original dataset showed the highest accuracy (86.4%, 95% confidence interval: 85.0–97.8%) compared to that of the doubled or tripled dataset. The total required number of images in this performance was only 2418 images. Gradient-weighted class activation mapping confirmed that the part that the deep-learning model pays attention to coincides with the part that the endoscopist pays attention to. Conclusion: As a result of a data-volume-dependent performance plateau in the classification model of colonoscopy, a dataset that has been doubled or tripled is not always beneficial to training. Deep-learning models would be more accurate if the proportion of fewer category lesions was increased.

Atherosclerosis, the major cause of myocardial infarction and stroke, results from converging inflammatory, metabolic, and biomechanical factors. Arterial lesions form at sites of low and disturbed blood flow but are suppressed by high laminar shear stress (LSS) mainly via transcriptional induction of the anti-inflammatory transcription factor, Kruppel-like factor 2 (Klf2). We therefore performed a whole genome CRISPR-Cas9 screen to identify genes required for LSS induction of Klf2. Subsequent mechanistic investigation revealed that LSS induces Klf2 via activation of both a MEKK2/3–MEK5–ERK5 kinase module and mitochondrial metabolism. Mitochondrial calcium and ROS signaling regulate assembly of a mitophagy- and p62-dependent scaffolding complex that amplifies MEKK–MEK5–ERK5 signaling. Blocking the mitochondrial pathway in vivo reduces expression of KLF2-dependent genes such as eNOS and inhibits vascular remodeling. Failure to activate the mitochondrial pathway limits Klf2 expression in regions of disturbed flow. This work thus defines a connection between metabolism and vascular inflammation that provides a new framework for understanding and developing treatments for vascular disease.

Introduction: Defective clearance of apoptotic cells (ACs) by macrophages (efferocytosis) contributes to unresolved inflammation. Our recent genome-wide CRISPR screen has discovered WDFY3 as a novel regulator required for the efficient uptake of ACs during efferocytosis. WDFY3 is well known as a scaffold protein facilitating the autophagic degradation of aggregated proteins in neurons. Yet, if and how WDFY3 may also be required for the efficient degradation of engulfed ACs by macrophages have not been characterized. Hypothesis: WDFY3 is responsible for the efficient degradation of ACs by interacting with other autophagic proteins to facilitate phagosome-lysosome fusion, a process known as LC3-associated phagocytosis (LAP). Methods: Bone marrow-derived macrophages (BMDMs), peritoneal macrophages (PMs), and mice with myeloid-specific Wdfy3 knockout (LysMCre +/- Wdfy3 fl/fl ) or transgenic overexpression of human WDFY3 ( hWDFY3 Tg ) were used for in vitro and in vivo assays. Results: Wdfy3 knockout BMDMs and PMs showed impaired lysosomal acidification and degradation of engulfed ACs. Mechanistically, Wdfy3 knockout impedes efficient LC3 lipidation upon AC engulfment, the last step required for phagosome-lysosome fusion and subsequent lysosomal degradation. Pull-down assay supports that WDFY3 interacts with GABARAP, but not LC3B, to mediate LC3 lipidation, supporting the direct involvement of WDFY3 protein in the process. At the transcriptomic level, RNA-seq and pathway analyses further revealed that gene sets of ROS/RNS production by phagocytes, fatty acid oxidation, and autophagosome were enriched in differentially expressed genes downregulated in Wdfy3 knockout BMDM, supporting the secondary effects of WDFY3-deficiency on the mRNA expression of genes and pathways essential for cargo degradation. Intriguingly, BMDMs and PMs from hWDFY3 Tg mice showed enhanced AC uptake and degradation both in vitro and in vivo , suggesting that WDFY3 has a wide dynamic range in its regulatory capacity. Conclusion: We discovered a novel role of WDFY3 in the degradation of ACs during macrophage efferocytosis. Enhancing WDFY3 may represent a therapeutic approach to promote the resolution of inflammation in diseases due to defective efferocytosis.

Endoscopic submucosal dissection (ESD) criteria are histologically categorized by early gastric cancer (EGC) with differentiated- and undifferentiated-type histology. However, EGC is histologically heterogenous and there have been no separate criteria for EGC with mixed-type histology [EGC-MH; differentiated-type predominant EGC mixed with an undifferentiated component (EGC-MD) or undifferentiated-type predominant EGC mixed with a differentiated component (EGC-MU)]. Moreover, therapeutic outcomes of ESD for EGC-MH have not been clearly described.This study aimed to evaluate the feasibility of ESD for EGC-MH.We searched core databases for specific inclusion factors: patients with EGC-MH, intervention of ESD, and at least one of the following outcomes: rate of en bloc, complete, curative resection, recurrence, procedure-related adverse event, lymphovascular invasion (LVI), or lymph node metastasis (LNM) that enabled evaluation of feasibility of ESD.A total of eight (systematic review) and four studies (meta-analysis) were included. There was no robustness in age, location, or morphology of EGC-MH. Moderately differentiated adenocarcinoma was frequent in pre-ESD biopsy. EGC-MH showed larger size, deeper invasion, and higher rates of LVI/LNM than pure-type EGC. Total en bloc, complete resection, and curative resection rates were 94.6% (95% confidence interval 86.6-97.9%), 77.8% (57.9-89.9%), and 55.1% (50.4-59.6%), respectively. There was no LNM or extra-gastric recurrence after ESD if the EGC-MD met the curative resection criteria. However, the EGC-MD itself was a risk factor for non-curative resection. (Margin positivity was the most common reason.) CONCLUSIONS: Although ESD seems to be technically feasible, inaccurate prediction of lateral or vertical margin leads to lower curative resection rate. Application of more strict indication is needed for EGC-MH.

Although alcohol intake is known to be associated with the development of colorectal cancer, the effect of alcohol consumption on the development of colorectal neoplasm (CRN) is unclear. We performed a retrospective cohort analysis with 1 to 1 propensity score matching in a single center of Korea. Among 1,448 patients who underwent index and surveillance colonoscopy, 210 matched pairs were analyzed. The 5-year cumulative occurrence of overall CRN after index colonoscopy was higher in the significant alcohol consumption group (defined as alcohol consumption more than 30 g/day in men and 20 g/day in women) (vs. without significant alcohol consumption group) (40% vs. 27.6%, p = 0.004). Significant alcohol consumption increased the development of overall CRN (adjusted hazard ratio [aHR]: 1.86, 95% confidence interval [CI]: 1.28–2.70, p = 0.001) at surveillance colonoscopy. However, this effect was not valid on the development of advanced CRN. In subgroup analysis considering the risk classification of index colonoscopy, significant alcohol consumption increased the overall CRN development at surveillance colonoscopy in the normal group (patients with no detected adenoma in the index colonoscopy) (aHR: 1.90, 95% CI: 1.16–3.13, p = 0.01). Alcohol consumption habits should be considered in optimizing time intervals of surveillance colonoscopy.

Although macroautophagy deficits are implicated across adult-onset neurodegenerative diseases, we understand little about how the discrete, highly evolved cell types of the central nervous system use macroautophagy to maintain homeostasis. One such cell type is the oligodendrocyte, whose myelin sheaths are central for the reliable conduction of action potentials. Using an integrated approach of mouse genetics, live cell imaging, electron microscopy, and biochemistry, we show that mature oligodendrocytes require macroautophagy to degrade cell autonomously their myelin by consolidating cytosolic and transmembrane myelin proteins into an amphisome intermediate prior to degradation. We find that disruption of autophagic myelin turnover leads to changes in myelin sheath structure, ultimately impairing neural function and culminating in an adult-onset progressive motor decline, neurodegeneration, and death. Our model indicates that the continuous and cell-autonomous maintenance of the myelin sheath through macroautophagy is essential, shedding insight into how macroautophagy dysregulation might contribute to neurodegenerative disease pathophysiology.

Clarithromycin resistance is a main factor for treatment failure in the context ofThis was a multicenter, randomized, controlled trial. A total of 782 patients withThe overall genotypic clarithromycin resistance rate was 25.7% according to the sequencing method. The eradication rate of 14-day bismuth-based quadruple therapy was not significantly different in the intention-to-treat analysis (80.4% vs 69.7%, p=0.079), but was significantly higher than that of 14-day metronidazole-intensified triple therapy in the per-protocol analysis (95.1% vs 76.4%, p=0.001). There were no significant differences in the incidence of side effects. In addition, the 14-day bismuth-based quadruple therapy was more cost-effective than the 14-day metronidazole-intensified triple therapy.Fourteen-day bismuth-based quadruple therapy showed comparable efficacy with 14-day metronidazole-intensified triple therapy, and it was more cost-effective in the context of clarithromycin-resistant

Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus, is threatening global health worldwide with unprecedented contagiousness and severity. The best strategy to overcome COVID-19 is a vaccine. Various vaccines are currently being developed, and mass vaccination is in progress. Despite the very encouraging clinical trial results of these vaccines, there is insufficient information on the safety and efficacy of vaccines for inflammatory bowel disease (IBD) patients facing various issues. After reviewing current evidence and international guidelines, the Korean Association for the Study of Intestinal Diseases (KASID) developed an expert consensus statement on COVID-19 vaccination issues for Korean IBD patients. This expert consensus statement emphasizes that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination be strongly recommended for IBD patients, and it is safe for IBD patients receiving immunomodulatory therapy.

The prevalence of osteoporosis and sarcopenia is significantly higher in patients with liver disease than in those without liver disease and osteoporosis and sarcopenia negatively influence morbidity and mortality in liver disease, yet these musculoskeletal disorders are frequently overlooked in clinical practice for patients with chronic liver disease. The objective of this review is to provide a comprehensive understanding of the molecular mechanisms of musculoskeletal disorders accompanying the pathogenesis of liver disease. The increased bone resorption through the receptor activator of nuclear factor kappa (RANK)-RANK ligand (RANKL)-osteoprotegerin (OPG) system and upregulation of inflammatory cytokines and decreased bone formation through increased bilirubin and sclerostin and lower insulin-like growth factor-1 are important mechanisms for osteoporosis in patients with liver disease. Sarcopenia is associated with insulin resistance and obesity in non-alcoholic fatty liver disease, whereas hyperammonemia, low amount of branched chain amino acids, and hypogonadism contributes to sarcopenia in liver cirrhosis. The bidirectional crosstalk between muscle and bone through myostatin, irisin, β-aminoisobutyric acid (BAIBA), osteocalcin, as well as the activation of the RANK and the Wnt/β-catenin pathways are associated with osteosarcopenia. The increased understandings for these musculoskeletal disorders would be contributes to the development of effective therapies targeting the pathophysiological mechanism involved.

Background: Clarithromycin resistance is a main factor for treatment failure in Helicobacter pylori infection. However, the treatment regimen for clarithromycin-resistant H. pylori infection has not yet been determined. Here, we aimed to compare the efficacy and cost-effectiveness of bismuth-based quadruple therapy versus metronidazole-intensified triple therapy with increased the dose and duration for clarithromycin-resistant H. pylori infection. Methods: This was a multicenter, randomized, controlled trial. A total of 782 patients with H. pylori infection examined using sequencing-based clarithromycin resistance point mutation tests were recruited between December 2018 and October 2020 in four institutions in Korea. Patients with significant point mutations (A2142G, A2142C, A2143G, A2143C, and A2144G) were randomly assigned to receive either 14-day bismuth-based quadruple therapy (n=102) or 14-day metronidazole-intensified triple therapy (n=99). Findings: The overall H. pylori eradication rate was 81.5% in the intention-to-treat analysis. The overall clarithromycin resistance rate was 25.7%. The eradication rate of 14-day bismuth-based quadruple therapy was not significantly different in the ITT analysis (80.4% vs. 69.7%, P =0.079), but was significantly higher than the 14-day metronidazole-intensified triple therapy in the per protocol analysis (95.1% vs. 76.4%, P =0.001). There were no significant differences in the incidence of side effects. Compared with empirical clarithromycin-based triple therapy, the 14-day bismuth-based quadruple therapy is more cost-effective than the 14-day metronidazole-intensified triple therapy. Interpretation: The 14-day bismuth-based quadruple therapy showed comparable efficacy with 14-day metronidazole-intensified triple therapy, and it was more cost-effective in the clarithromycin-resistant H. pylori infection. Clinical Trial Registration Details: This study was registered with the Clinical Trials Registry (NCT03431688). Funding Information: Dong-A ST. Declaration of Interests: None. Ethics Approval Statement: The study was approved by the ethics committee of four institutions, and was approved by the ethical guidelines of the Declaration of Helsinki (IRB no. 2018-01-015 for Kangdong Sacred Heart Hospital, 2018-04-007 for Hallym University Sacred Heart Hospital, 2018-04-043 for Chuncheon Sacred Heart Hospital, and 2018-11-009 for Dongtan Sacred Heart Hospital).

Background: Classification of colorectal neoplasms during colonoscopic examination is important to avoid unnecessary endoscopic biopsy or resection. This study aimed to develop and validate deep learning models that automatically classify colorectal lesions histologically on white-light colonoscopy images. Methods: White-light colonoscopy images of colorectal lesions exhibiting pathological results were collected and classified into seven categories: stages T1-4 colorectal cancer (CRC), high-grade dysplasia (HGD), tubular adenoma (TA), and non-neoplasms. The images were then re-classified into four categories including advanced CRC, early CRC/HGD, TA, and non-neoplasms. Two convolutional neural network models were trained, and the performances were evaluated in an internal test dataset and an external validation dataset. Results: In total, 3828 images were collected from 1339 patients. The mean accuracies of ResNet-152 model for the seven-category and four-category classification were 60.2% and 67.3% in the internal test dataset, and 74.7% and 79.2% in the external validation dataset, respectively, including 240 images. In the external validation, ResNet-152 outperformed two endoscopists for four-category classification, and showed a higher mean area under the curve (AUC) for detecting TA+ lesions (0.818) compared to the worst-performing endoscopist. The mean AUC for detecting HGD+ lesions reached 0.876 by Inception-ResNet-v2. Conclusions: A deep learning model presented promising performance in classifying colorectal lesions on white-light colonoscopy images, this model could help endoscopists build optimal treatment strategies.

The optimal treatment regimen or the duration of treatment for an endoscopic submucosal dissection (ESD)-induced gastric ulcer has not been established. The aim of this study was to assess the efficacy of novel proton-pump inhibitor, ilaprazole, for the treatment of ESD-induced gastric ulcer. This was a prospective, open-label, randomized multicenter study. Between June 2015 and March 2018, a total of 176 patients (178 lesions) who underwent ESD for a gastric neoplasm were randomly allocated to receive the oral proton-pump inhibitor ilaprazole 20 mg or rabeprazole 20 mg daily for 8 weeks. The primary outcome was the ulcer healing rate at 4 and 8 weeks. A total of 155 (157 lesions) and 154 patients (156 lesions) were included in the modified intention-to-treat (mITT) and per-protocol analyses, respectively. There was no significant difference in the ulcer healing rate (ilaprazole vs. rabeprazole, 97.4% vs. 97.0 p = 0.78 at 4 weeks, 100% vs. 100%, p = 0.95 at 8 weeks in the mITT analysis) or stage of ulcer (scar stage, 25.6% vs. 17.7%, p = 0.25 at 4 weeks, 92.3% vs. 88.6%, p = 0.59 at 8 weeks in the mITT analysis) between the treatment groups. The quality of ulcer healing was not significantly different between the two groups. No independent predictive factor for higher-quality ulcer healing was found in the multivariate analysis. According to this trial, ilaprazole and rabeprazole showed no significant difference in the healing of artificial gastric ulcers. Most of the ulcers achieved complete healing within 4–8 weeks. Trial registration: ClinicalTrial.gov NCT02638584.

The forward-viewing endoscope has been increasingly used to perform endoscopic retrograde cholangiopancreatography (ERCP) in patients who underwent Billroth II gastrectomy. This study intended to assess efficacy and safety of the forward-viewing endoscope for ERCP in Billroth II gastrectomy patients compared with conventional side-viewing endoscope using a systematic review and meta-analysis. A systematic review was conducted for studies that evaluated the outcomes of ERCP for patients with Billroth II gastrectomy. Random-effect model meta-analyses with subgroup analyses were conducted. The methodological quality of the included publications was evaluated using the risk of bias assessment tool for non-randomized studies. The publication bias was assessed. In total, 25 studies (1 randomized, 18 retrospective, 1 prospective, and 5 case series studies) with 2446 patients (499 forward-viewing and 1947 side-viewing endoscopes) were analyzed. The pooled afferent loop intubation rate was higher with the forward-viewing endoscope (90.3%, 95% confidence interval (CI) 85.6–93.6 vs. 86.8%, 95% CI 82.8–89.9%). The pooled selective cannulation rate was higher with the side-viewing endoscope (92.3%, 95% CI 88.0–95.2 vs. 91.1%, 95% CI 87.2–93.9%). The pooled bowel perforation rate was higher with the side-viewing endoscope (3.6%, 95% CI 2.3–5.7 vs. 3.0%, 95% CI 1.7–5.3%). The pooled pancreatitis rate was higher with the forward-viewing endoscope (5.4%, 95% CI 3.6–8.0 vs. 2.5%, 95% CI 2.3–5.7%). The pooled bleeding rate was higher with the forward-viewing endoscope (3.0%, 95% CI 1.6–5.5 vs. 2.0%, 95% CI 1.4–3.0%). The heterogeneity among the studies was not significant. The publication bias was minimal. This meta-analysis indicates that the forward-viewing endoscope is as safe and effective as conventional side-viewing endoscope for ERCP in patients with Billroth II gastrectomy.

Background Visual inspection, lesion detection, and differentiation between malignant and benign features are key aspects of an endoscopist’s role. The use of machine learning for the recognition and differentiation of images has been increasingly adopted in clinical practice. This study aimed to establish convolutional neural network (CNN) models to automatically classify gastric neoplasms based on endoscopic images. Methods Endoscopic white-light images of pathologically confirmed gastric lesions were collected and classified into five categories: advanced gastric cancer, early gastric cancer, high grade dysplasia, low grade dysplasia, and non-neoplasm. Three pretrained CNN models were fine-tuned using a training dataset. The classifying performance of the models was evaluated using a test dataset and a prospective validation dataset. Results A total of 5017 images were collected from 1269 patients, among which 812 images from 212 patients were used as the test dataset. An additional 200 images from 200 patients were collected and used for prospective validation. For the five-category classification, the weighted average accuracy of the Inception-Resnet-v2 model reached 84.6 %. The mean area under the curve (AUC) of the model for differentiating gastric cancer and neoplasm was 0.877 and 0.927, respectively. In prospective validation, the Inception-Resnet-v2 model showed lower performance compared with the endoscopist with the best performance (five-category accuracy 76.4 % vs. 87.6 %; cancer 76.0 % vs. 97.5 %; neoplasm 73.5 % vs. 96.5 %; P Conclusion The evaluated deep-learning models have the potential for clinical application in classifying gastric cancer or neoplasm on endoscopic white-light images.

The gastrointestinal endoscopy unit is frequently exposed to gastrointestinal gas expelled from patients and electrocoagulated tissue through carbonation. This can be potentially harmful to the health of not only the healthcare personnel but also patients who undergo endoscopy. This study aimed to measure the air quality in the endoscopy unit. We measured indoor air quality indices (CO2, total volatile organic compounds (VOCs), PM2.5, NO2, CO, and ozone) using portable passive air quality monitoring sensors in the procedural area, recovery area, and cleansing-of-equipment area, at 1-min intervals for 1 week, and the type and number of endoscopic procedures were recorded. CO2, PM2.5, NO2, and ozone levels were the highest in the cleansing area, followed by the procedural and recovery areas, and VOC level was highest in the procedural area. The proportion of poor-quality level of CO2 and VOCs was highest in the procedural area and that of NO2 was highest in the cleansing area. The proportion of tolerable to poor-quality (exceeding acceptable level) level of CO2 and total VOCs in the procedural area was 26% and 19.2% in all measurement times, respectively. The proportion of tolerable to poor-quality level of NO2 in the cleansing area of the endoscopy unit was 32.1% in all measurement times. Multivariate analyses revealed that tolerable to poor-quality (exceeding acceptable level) level of VOCs was associated with the number of endoscopic procedures (odds ratio, 1.79; 95% confidence interval, 1.42–2.27) and PM2.5 level (1.27, 1.12–1.44). Moreover, tolerable to poor-quality level of CO2 was associated with the number of colonoscopy (5.35, 1.19–24.02), especially with electrocoagulation procedures (24.31, 1.31–452.44) in the procedural area. Healthcare personnel and patients who undergo endoscopy are frequently exposed to ambient air pollution. Health-related protective strategies for ambient air pollution in the endoscopy unit are warranted. NCT03724565.

Background/Aim: Endoscopic retrograde cholangiopancreatography (ERCP) is typically performed in prone position. In cases of difficulty in prone position, ERCP can be performed in left lateral position. We aimed to evaluate the efficacy and safety of left lateral position for ERCP compared with those of prone position. Patients and Methods: Between August 2015 and March 2016, a total of 62 patients with native papilla who underwent ERCP were randomly assigned to undergo the procedure in left lateral position (n = 31) or prone position (n = 31). The outcomes of procedures were compared between the two groups. Results: There were no significant differences between the two groups in terms of the demographic data, indications for ERCP, comorbidities, anticoagulation agents, the types and doses of sedative agents, and procedural durations. The rates of technical success and adverse events were similar (96.8 and 40%, respectively, in left lateral group and 100 and 32.3%, respectively, in prone group). The rates of unintentional pancreatic duct (PD) cannulation and the acquisition of pancreatograms in left lateral group were significantly greater than those in prone group (9/30, 30.0% vs. 3/31, 9.7%, P = 0.046; 7/30, 23.3% vs. 1/31, 3.2%, P = 0.020, respectively). However, there was no significant difference in the rate of post-ERCP pancreatitis (6/30, 20% vs. 5/31, 16.1%, P = 0.694). Conclusion: The left lateral position for ERCP can be as effective and safe as prone position. Due to increased rates of unintended PD cannulation and contrast injection, the initial use of left lateral position may be limited to cases that exhibit difficulty in prone position.

The aim of this study was to identify the effect of selective estrogen receptor modulator (SERM) on non-alcoholic fatty liver disease (NAFLD) in Asian women.We retrospectively evaluated fatty liver development and/or serum alanine aminotransferase (ALT) elevation during SERM treatment in 1061 women who were diagnosed and treated with breast cancer in 2005 at Asan Medical Center.45 of 618 SERM-treated patients with normal ALT at baseline experienced ALT elevation during SERM treatment. Among the 112 SERM-treated patients who underwent liver imaging test, fatty liver was observed in 47 and both fatty liver and ALT elevation developed in 16 of 102 SERM-treated patients with normal baseline ALT. The cumulative rates of ALT elevation (10.7 vs. 4.3%; P = 0.002), fatty liver (48.5 vs. 20.9%; P 0.001), and both fatty liver and ALT elevation (17.7 vs. 7.1%; P = 0.02) at 60 months were significantly higher in the SERM group than non-SERM group. By multivariate analysis, SERM treatment increased the risk of ALT elevation (hazard ratio [HR], 2.20; P = 0.01), fatty liver development (HR, 3.59; P 0.001), and both fatty liver and ALT elevation (HR, 4.98; P = 0.01). After discontinuation of SERM, elevated serum ALT normalized in 39 (92.9%) and there were no instances of liver-related death or progression to liver cirrhosis in patients who experienced fatty liver or ALT elevation.Although SERM treatment is significantly associated with NAFLD in Asian women, considering the tolerability and reversibility of NAFLD induced by SERM, it can be continued with liver function monitoring in relevant patients.

Candidemia is a rare adverse event of endoscopic retrograde cholangiopancreatography (ERCP). To date, several case reports of post-ERCP candidemia have been reported. Recently, we experienced a case of disseminated candidemia caused by Candida albicans with secondary complications of acute respiratory distress syndrome, acute kidney injury, and hematogenous candidal endophthalmitis following ERCP in a young healthy patient without well-recognized risk factors for candidemia. After intravenous and intravitreal antifungal therapy and intensive care, the candidemia resolved, and the patient was discharged without further sequela. The present case alerted us to consider candidemia as a rare but potentially fatal adverse event of ERCP, even in an immunocompetent host.

Artificial intelligence (AI) using deep-learning (DL) has emerged as a breakthrough computer technology. By the era of big data, the accumulation of an enormous number of digital images and medical records drove the need for the utilization of AI to efficiently deal with these data, which have become fundamental resources for a machine to learn by itself. Among several DL models, the convolutional neural network showed outstanding performance in image analysis. In the field of gastroenterology, physicians handle large amounts of clinical data and various kinds of image devices such as endoscopy and ultrasound. AI has been applied in gastroenterology in terms of diagnosis, prognosis, and image analysis. However, potential inherent selection bias cannot be excluded in the form of retrospective study. Because overfitting and spectrum bias (class imbalance) have the possibility of overestimating the accuracy, external validation using unused datasets for model development, collected in a way that minimizes the spectrum bias, is mandatory. For robust verification, prospective studies with adequate inclusion/exclusion criteria, which represent the target populations, are needed. DL has its own lack of interpretability. Because interpretability is important in that it can provide safety measures, help to detect bias, and create social acceptance, further investigations should be performed.

Background: Melatonin generated in the gastrointestinal tract has mucosal protective effect with inhibiting gastric acid secretion, while increasing gastrin release, which in turn stimulates the contractility of lower esophageal sphincter. Gastroesophageal reflux disease (GERD) is also known to have association with sleep disturbance. However, melatonin or melatonin receptor agonist has not been included in the treatment of GERD. This study aimed to evaluate the efficacy of melatonin for the treatment of GERD. Methods: We will search the core databases [MEDLINE (through PubMed), the Cochrane Library, and Embase] from their inception to December 2018 by 2 independent evaluators. The P.I.C.O. is as follows; Patients: who have GERD, Intervention: melatonin or melatonin receptor agonist treatment, Comparison: patients without melatonin or melatonin receptor agonist treatment, Outcome: clinical indices (or crude number or proportion of improvement) for the evaluation of symptomatic improvement which enable comparison of efficacy between patients with melatonin or melatonin receptor agonist and the control group. All types of study design will be sought with full-text will be included. The risk of bias will be assessed using the ROBINS-I tool. Descriptive data synthesis is planned and quantitative synthesis will be used if the included studies are sufficiently homogenous. Publication bias will be assessed with quantitative analyses if more than 10 articles are enrolled. Results: The results will provide evidence for the efficacy of melatonin or melatonin receptor agonist for the treatment of GERD. Conclusion: This study will provide evidence of melatonin or melatonin receptor agonist treatment for GERD.

Understanding the fundamental mechanism underlying the accumulation and clearance of misfolded proteins can lead to insights into the synthetic and degradative pathways that maintain the homeostasis of proteins in all cells. Given the interconnection between protein homeostasis and cell health, as well as the complexity of aggregate formation and the degradation pathways with which it is intertwined, the design of the tools that are used to examine protein aggregation and accumulation can have a profound impact on the interpretation of results. We rely on two previously published stable cell lines that use conditional expression and the ligand-receptor tag known as HaloTag, to temporally distinguish distinct pools of aggregates, and use a combination of biochemical- and imaging-based methods to measure aggregation of a canonical aggregation-prone protein. We measure aggregate load biochemically using Filter Trap Analysis, which combines a filter trap retardation assay and immunoblotting to measure detergent soluble and insoluble protein levels, and visually, using confocal microscopy to monitor simultaneously aggregate formation and growth events in the background of aggregate clearance. As a secondary screen to more simplistic screen based approaches, this method permits further insight into how aggregate load is affected.

Understanding the fundamental mechanism underlying the accumulation and clearance of misfolded proteins can lead to insights into the synthetic and degradative pathways that maintain the homeostasis of proteins in all cells. Given the interconnection between protein homeostasis and cell health, as well as the complexity of aggregate formation and the degradation pathways with which it is intertwined, the design of the tools that are used to examine protein aggregation and accumulation can have a profound impact on the interpretation of results. We rely on two previously published stable cell lines that use conditional expression and the ligand-receptor tag known as HaloTag, to temporally distinguish distinct pools of aggregates, and use a combination of biochemical- and imaging-based methods to measure aggregation of a canonical aggregation-prone protein. We measure aggregate load biochemically using Filter Trap Analysis, which combines a filter trap retardation assay and immunoblotting to measure detergent soluble and insoluble protein levels, and visually, using confocal microscopy to monitor simultaneously aggregate formation and growth events in the background of aggregate clearance. As a secondary screen to more simplistic screen based approaches, this method permits further insight into how aggregate load is affected.

Antibiotic resistance is growing worldwide, and patients who have failed consecutive 1st- and 2nd-lineH. pylorieradication regimens are increasing. Therefore, the role of the bacterial culture with antibiotic susceptibility testing and molecular susceptibility testing is important for avoiding the use of ineffective antibiotics. However, antibiotic susceptibility testing-guided treatment does not necessarily guarantee successful eradication, and there have been mixed results for the effectiveness of a 3rd-line rescue therapy. Therefore, providing patients with pretreatment medication instructions and education is important. It is also crucial to determine the reason of the eradication failure, including host-related factors (poor compliance to eradication regimen, smoking, and cytochrome P450 2C19 genetic polymorphism) or treatment-related factors (inadequate dosage or duration of therapy and gastric acidity), as such factors can be modified for a tailored therapy. Although the indications forH. pylorieradication have widened, patients at a high risk of gastric cancer can gain definitive benefits with a 3rd-line or even 4th-line therapy.