Drug-induced liver injury (DILI) is a drug-induced disease that not only complicates the treatment of the primary disease but may also lead to acute liver failure or even death in severe cases. Drugs commonly used in primary care, such as anti-infective agents and nonsteroidal anti-inflammatory drugs, are major causes of DILI. In addition, a large elderly population, comorbidities, and combination therapy with multiple drugs increase the risk of DILI in primary care. Therefore, primary care providers should proactively screen and monitor high-risk patients to identify potential DILI timely. Currently, diagnosis of DILI relies on the exclusion of liver diseases of other etiologies. Collection of detailed medical history of the patients and careful exclusion of other potential liver injury of other etiologies are crucial for accurate diagnosis. This guideline, developed based on evidence-based medicine from the latest research, aimed to provide primary care providers with professional guidance on the timely identification of suspected DILI cases and standardized diagnosis and management in clinical practice.

Gastric cardiac carcinoma (GCC), also known as gastroesophageal junction (GEJ) carcinoma, is a slow-growing fatal cancer that arises in gastric cardiac mucosa in a region of about 2 cm above and 3 cm below the GEJ line. This carcinoma shows clinicopathologic and genomic features similar, but not identical, to gastric noncardiac carcinoma (GNCC). In contrast, GCC is much more complicated than esophageal adenocarcinoma (EA) in clinicopathology, genomics, and prognosis. GCC is heterogeneous geographically, accounting for 20%–50% of all gastric carcinomas in endemic regions in China. Compared with EA, GCC shows a much broader histopathologic spectrum and worse prognosis. Although detailed mechanisms of GCC pathogenesis remain elusive, advanced age, Helicobacter pylori infection, and gastroesophageal reflux disease are key risk factors. Intriguingly, goblet cell intestinal metaplasia may not be an essential initial step toward carcinogenesis in all GCC cases. At present, an accurate diagnosis of early GCC with prompt curative resection is the only realistic hope for dramatically improving patient outcomes. The recently developed liquid biopsy technology for serum cell-free DNA is a promising tool for the detection of early GCC, though many challenges remain and an in-depth investigation is required. Given the recent rapid advances in artificial intelligence, endoscopic technology, and a better understanding of endoscopists for subtle mucosal/vascular changes in early GCC, accurate detection of early GCC in a high proportion of cases would be possible.

Objectives: Etiological therapy has been documented to improve portal hypertension. We aimed to analyze the effectiveness of etiological therapy on hepatic venous pressure gradient (HVPG) reduction by conducting a systematic review and meta-analysis.

Methods: Literature search of the PubMed, EMBASE, and Cochrane Library was performed to identify studies involving patients with PHT published up to January 2024. The absolute HVPG reduction and the HVPG response rate were assessed. Pooled analyses were performed using random-effects models, and the heterogeneity was evaluated using sensitivity and subgroup analyses.

Results: Altogether 21 studies were included for analysis. After etiological therapy, the absolute reduction in HVPG was 2.25 mmHg (95% confidence interval [CI] 1.80–2.71). Longer (> 1 year) duration of etiological therapy showed more significant HVPG reduction compared with those treated with 1 year or less (3.02 mmHg vs. 2.24 mmHg, p = 0.001). A more pronounced HVPG reduction was also observed in patients with viral hepatitis-induced cirrhosis than in those with non-viral hepatitis-induced cirrhosis (2.39 mmHg vs. 1.27 mmHg, p = 0.001). Furthermore, 64% and 41% of patients showed ≥ 10% HVPG reduction and a reduction of ≥ 20% or to ≤ 12 mmHg, respectively, after etiology control.

Conclusion: Effective etiology control can significantly decrease HVPG and increase the HVPG response rate, which may contribute to the improvement of the prognosis of cirrhotic patients.

Objectives: Double-balloon enteroscopy (DBE) is effective for managing small bowel (SB) diseases. We aimed to evaluate the patient outcomes of DBE polypectomy in Peutz–Jeghers syndrome (PJS) with large SB polyps at surveillance imaging studies and to identify the risk factors for SB surgery.

Methods: Forty-five PJS patients who underwent regular SB surveillance imaging studies from 2005 to 2023 were retrospectively included. DBE was performed for polyps > 15 mm detected by imaging studies, and DBE polypectomy was conducted for those > 10 mm or symptomatic ones.

Results: Patients' average age at PJS diagnosis and surveillance initiation was 19.9 and 27.8 years, respectively. Thirty-one (68.9%) patients had laparotomy before surveillance. Each patient underwent 2.7 DBE procedures at a 31.0-month interval. An average of 7.8 and 4.4 polyps were removed during the first and second DBE procedures (p = 0.070). During 9 (8.2%) DBE procedures, complications, including two perforations requiring surgery, occurred. During the follow-up period, 11 patients required SB surgery, with a median time to surgery of 155 months. Patients with ≥ 5 polyps removed at initial DBE had a higher cumulative probability of SB surgery than those with < 5 polyps (hazard ratio [HR] 9.65, p = 0.031). Patients with ≥ 3 laparotomies before surveillance tended to have an increased surgery risk (HR 9.98, p = 0.078).

Conclusions: DBE polypectomy effectively manages large SB polyps detected by imaging surveillance in PJS over the long term. Early initiation of surveillance should be emphasized to minimize the risk of SB surgery.

Objective: We aimed to evaluate the effect of primary sclerosing cholangitis (PSC) on hospitalization outcomes of inflammatory bowel disease (IBD) patients.

Methods: This retrospective study used data from the Nationwide Inpatient Sample (NIS) database from January 1, 2019, to December 31, 2020, including adults (≥ 18 years) admitted and diagnosed with IBD. Key outcomes included length of hospital stay (LOS), in-hospital mortality, hospitalization cost, and complications. The propensity score matching (PSM) analysis was used to balance characteristics between IBD patients with and without PSC, followed by logistic regression for analysis.

Results: After PSM analysis, 4950 patients (PSC: 990; non-PSC: 3960) were analyzed. IBD patients with PSC showed higher odds of any complication (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.80–2.39), including acute kidney injury (OR 1.31, 95% CI 1.10–1.55), septic shock (OR 1.84, 95% CI 1.33–2.54), liver cirrhosis (OR 18.19, 95% CI 14.23–23.25), and liver failure (OR 8.33, 95% CI 5.93–11.70) (all p < 0.05). These associations were consistently observed across subgroups with stronger associations in the Crohn's disease subgroup.

Conclusions: PSC significantly increases the risk of short-term complications in hospitalized IBD patients and the likelihood of chronic liver disease-related complications. These findings highlight the need for targeted management strategies for IBD patients with co-existing PSC.

Objectives: Designer receptors exclusively activated by designer drugs (DREADDs)-based chemogenetic tools are commonly used to activate or silence targeted neurons by the agonistic ligand deschloroclozapine (DCZ). This study aimed to establish a Gi-DREADD-based murine model of slow transit constipation (STC) and elucidate its pathophysiological mechanisms.

Methods: Adeno-associated virus (AAV) 9-hM4Di was injected into the intestinal wall of mice, and colonic motility was evaluated. The efficiency and immunogenicity of AAV9-hM4Di transduction in the enteric nervous system (ENS) were evaluated. Nitric oxide (NO), acetylcholine (ACh), and substance P (SP) in the colonic tissues and serum samples were analyzed. Calcium (Ca²⁺) imaging was performed to evaluate the responses of AAV9-hM4Di on enteric nerves.

Results: AAV9-hM4Di-treated mice showed gastrointestinal motility dysfunction, including reduced fecal pellets and decreased fecal mass and water content. Electrophysiological recording of muscle contraction in the isolated colonic tissues from the chemogenetic mice showed decreased frequency and amplitude after DCZ treatment. The mice treated with AAV9-hM4Di showed the highest levels of transduction in the myenteric plexuses of the ENS. There were no differences in transduction in neuronal nitric oxide synthase (nNOS) and choline acetyltransferase (ChAT) neurons. Gi-DREADDs significantly downregulated ACh but not NO or SP expression in the distal colon in the chemogenetic mice. Ca²⁺ transient in neurons of ENS in chemogenetic mice was strongly inhibited by DCZ.

Conclusions: It is feasible to apply the DREADDs-based chemogenetic tools to the ENS. Gi-DREADDs can selectively modulate the ENS, inducing STC without excitatory-neural bias, offering targeted neuromodulation for gastrointestinal motility disorders.

Objectives: In this study, we aimed to evaluate the effectiveness of a novel endoscopic purse-string suture auxiliary instrument compared with traditional methods for closure of a full-thickness defect of the stomach in an ex vivo model.

Methods: Twelve perforation sites (10–20 mm in diameter) were created in the ex vivo porcine stomach models. Two physicians (A and B had performed endoscopic surgery for 6 and 3 years) performed suturing using both the experimental and traditional (control) instruments. Operation time, success rate, and number of attempts for successful suture required were recorded.

Results: For physician A, the median suturing time was 56.50 s (interquartile range [IQR] 40.50 s, 134.50 s) and 215.50 s (IQR 63.75 s, 254.75 s) in the experimental and control groups. For physician B, they were 53.00 s (IQR 38.50 s, 87.75 s) and 174.00 s (IQR 104.50 s, 279.25 s), respectively. The differences between experimental and control groups were statistically significant for both physicians A (p = 0.010) and B (p = 0.004). The median number of attempts required for successful suturing in the experimental and control groups was 1 (IQR 1, 2) and 2 (IQR 1, 3) for physician A, and 1 (IQR 1, 1) and 3 (IQR 2, 3) for physician B, which were statistically significant for both physicians (p = 0.026 and 0.006). The overall success rate was significantly higher in the experimental group (100% vs. 75.0%, p = 0.022).

Conclusion: This novel purse-string suture auxiliary instrument may assist in single-channel endoscopic suturing operations, improve the suture success rate, reduce the number of operations required, and shorten the operation time.

Objective: This study aimed to develop a computer-aided diagnosis (CADx) model using an automated deep learning (DL) program to classify low- and high-risk adenomas among colorectal polyps ≤ 10 mm with standard white-light endoscopy.

Methods: Still images of colorectal adenomas ≤ 10 mm were extracted. High-risk adenomas were defined as high-grade dysplasia or adenomas with villous histology. Neuro-T version 3.2.1 (Neurocle Inc., Seoul, Republic of Korea), an automated DL software, was used for DL. Accuracy, precision, recall, and F1 score of the DL model were calculated. Endoscopy experts and trainees were invited to diagnose endoscopic images to compare their diagnostic accuracy with that of the DL model.

Results: A total of 2696 endoscopic images (2460 images of low-grade and 236 of high-grade adenomas) were used for training the DL model. In classifying high- and low-risk adenomas in the external validation dataset (398 images of low-grade and 41 images of high-grade adenomas), the model demonstrated 93.8% accuracy, 81.0% precision, 85.7% recall, and 83.3% F1 score overall. The area under the receiver operating characteristic curve for classifying high- and low-risk adenomas was 0.910 and 0.914, respectively. The expert endoscopists and trainees showed an overall accuracy of 95.1% and 79.7%, respectively, for discriminating high- and low-risk adenomas in the external validation dataset.

Conclusions: The CADx model established by the automated DL program showed high diagnostic performance in differentiating high- and low-risk adenomas among colorectal polyps ≤ 10 mm. The performance of the model was comparable to the experts and superior to the trainees.