Au-doped MOFs catalyzed electrochemiluminescence platform coupled with target-induced self-enrichment for detection of synthetic cannabinoid RCS-4.

A ternary composite material with Au, Co-based organic frameworks (ZIF-67) and perylene derivatives (PTCD-cys) has been synthesized for identification of synthetic cannabinoids. Through contact with Au-S, Au-ZIF-67 increased electrochemiluminescence (ECL) sensitivity and stability and efficiently catalyzed the ECL of PTCD-cys. Compared with the ECL response of PTCD-cys monomer, the ECL signal value of the composite material was significantly increased, and the onset potential of Au-ZIF-67/PTCD-cys favorably shifted more than that of PTCD-cys/GCE. When the target cannabinoid molecule RCS-4 appeared, Au-ZIF-67 captured and immobilized it on the sensor surface by adsorption to achieve target-induced self-enrichment of RCS-4. Under optimal conditions, the ECL sensor was found to be linearly related to the logarithm of the RCS-4 concentration ranging from 3.1 × 10-15 to 3.1 × 10-9 mol/L with a detection limit (LOD) of 6.0 × 10-16 mol/L (S/N = 3). The approach had the advantages of being simple to use, having a high sensitivity, a wide detection range, and good stability, making it a novel platform for RSC-4 detection in public health safety monitoring.

PTCD1 Is Required for Mitochondrial Oxidative-Phosphorylation: Possible Genetic Association with Alzheimer's Disease.

In addition to amyloid-ß plaques and tau tangles, mitochondrial dysfunction is implicated in the pathology of Alzheimer's disease (AD). Neurons heavily rely on mitochondrial function, and deficits in brain energy metabolism are detected early in AD; however, direct human genetic evidence for mitochondrial involvement in AD pathogenesis is limited. We analyzed whole-exome sequencing data of 4549 AD cases and 3332 age-matched controls and discovered that rare protein altering variants in the gene pentatricopeptide repeat-containing protein 1 (PTCD1) show a trend for enrichment in cases compared with controls. We show here that PTCD1 is required for normal mitochondrial rRNA levels, proper assembly of the mitochondrial ribosome and hence for mitochondrial translation and assembly of the electron transport chain. Loss of PTCD1 function impairs oxidative phosphorylation and forces cells to rely on glycolysis for energy production. Cells expressing the AD-linked variant of PTCD1 fail to sustain energy production under increased metabolic stress. In neurons, reduced PTCD1 expression leads to lower ATP levels and impacts spontaneous synaptic activity. Thus, our study uncovers a possible link between a protein required for mitochondrial function and energy metabolism and AD risk.SIGNIFICANCE STATEMENT Mitochondria are the main source of cellular energy and mitochondrial dysfunction is implicated in the pathology of Alzheimer's disease (AD) and other neurodegenerative disorders. Here, we identify a variant in the gene PTCD1 that is enriched in AD patients and demonstrate that PTCD1 is required for ATP generation through oxidative phosphorylation. PTCD1 regulates the level of 16S rRNA, the backbone of the mitoribosome, and is essential for mitochondrial translation and assembly of the electron transport chain. Cells expressing the AD-associated variant fail to maintain adequate ATP production during metabolic stress, and reduced PTCD1 activity disrupts neuronal energy homeostasis and dampens spontaneous transmission. Our work provides a mechanistic link between a protein required for mitochondrial function and genetic AD risk.

Mitochondrial ribosomal protein PTCD3 mutations cause oxidative phosphorylation defects with Leigh syndrome.

Pentatricopeptide repeat domain proteins are a large family of RNA-binding proteins involved in mitochondrial RNA editing, stability, and translation. Mitochondrial translation machinery defects are an expanding group of genetic diseases in humans. We describe a patient who presented with low birth weight, mental retardation, and optic atrophy. Brain MRI showed abnormal bilateral signals at the basal ganglia and brainstem, and the patient was diagnosed as Leigh syndrome. Exome sequencing revealed two potentially loss-of-function variants [c.415-2A>G, and c.1747_1748insCT (p.Phe583Serfs*3)] in PTCD3 (also known as MRPS39). PTCD3, a member of the pentatricopeptide repeat domain protein family, is a component of the small mitoribosomal subunit. The patient had marked decreases in mitochondrial complex I and IV levels and activities, oxygen consumption and ATP biosynthesis, and generalized mitochondrial translation defects in fibroblasts. Quantitative proteomic analysis revealed decreased levels of the small mitoribosomal subunits. Complementation experiments rescued oxidative phosphorylation complex I and IV levels and activities, ATP biosynthesis, and MT-RNR1 rRNA transcript level, providing functional validation of the pathogenicity of identified variants. This is the first report of an association of PTCD3 mutations with Leigh syndrome along with combined oxidative phosphorylation deficiencies caused by defects in the mitochondrial translation machinery.

Identification of genes required for the spontaneous repair of partial-thickness cartilage defects in immature rats.

PURPOSE: Our previous study showed that partial-thickness articular cartilage defects (PTCDs) created in immature rats spontaneously healed to resemble normal hyaline cartilage, but that of mature rats did not. To identify molecules involved in the spontaneous cartilage repair observed in this model, gene expression was compared between PTCD and sham-operated cartilage of immature and mature rats. MATERIALS AND METHODS: Six sets of gene comparisons were made at 12, 24, and 48 hours after the creation of PTCDs in immature and mature rats using microarrays. All the genes upregulated in immature cartilage at 12 hours were selected for further analysis if their expression pattern was not irregular such that diminished at 24 hours and re-upregulated at 48 hours. Relationships among genes selected through the above steps were analyzed using Ingenuity Pathway Analysis (IPA) software. After deriving networks, important molecules were further narrowed down by location within a network. Genes were regarded as central if they had relationships with more than 10 molecules in a network. Protein localization in tissues was confirmed by immunohistochemistry. RESULTS: Five networks were identified. Their functional annotations were gene expression, cell cycle, growth and proliferation, and cell signaling. Transforming growth factor-beta (TGF-ß) was centrally located in the network with the highest IPA score and mothers against decapentaplegic homolog-3 (Smad3) were centrally located in the second highest ranking network. Phosphorylated Smad3 was detected in the nuclei of chondrocytes in immature cartilage. CONCLUSIONS: Our data suggest the possible importance of Smad3 in the TGF-ß signaling in the spontaneous healing of PTCDs in immature rats.

MRI-guided percutaneous transhepatic cholangiodrainage: feasibility study in a porcine model.

BACKGROUND AND STUDY AIMS: MRI-guided procedures combine high-quality imaging with lack of radiation. Percutaneous transhepatic cholangiodrainage under real-time MRI guidance (MRI-PTCD) seems promising, allowing targeted puncture and avoiding multiple blind passes and use of contrast, which are associated with standard PTCD's heaviest complications. PATIENTS AND METHODS: Aim of this study was to investigate the feasibility of MRI-PTCD in three outbred piglets. Obstructive cholestasis was induced by common bile duct ligation. Two days later, MRI-PTCD was performed (open MRI, 1.0 Tesla) with prototype MRI-compatible accessories. Visualization was achieved with a balanced steady-state free precession real-time sequence (bSSFP: 0.75 frames/s, TR/TE [ms]: 7.2/3.6; flip angle: 45°; 200 × 200 matrix size; resolution: 1.3 × 1.3 mm(2), slice thickness: 7 mm). Cannulation of the bile ducts was followed by placement of Yamakawa drainages. RESULTS: Twelve punctures were performed (four per animal, 10/12 successful); in 2/10 the bile ducts could not be cannulated. Animal survival was 100% and no significant complications occurred. CONCLUSIONS: Initial data show that MRI-PTCD can be successfully performed. This may lead to establishment of a new optimized PTCD technique compared to the standard approach under fluoroscopy.

Intraductal radiofrequency ablation plus biliary stent versus stent alone for malignant biliary obstruction: a systematic review and meta-analysis.

Background and study aims Recurrent biliary stent occlusion and tumor ingrowth remain a major concern among patients with malignant biliary obstruction (MBO) with significant impact on patient morbidity and survival. Intraductal radiofrequency ablation (RFA) has emerged as a promising treatment that seeks to extend stent patency. This study aimed to evaluate the impact of RFA on overall survival (OS) and stent patency among patients with unresectable MBO. Methods A comprehensive search of electronic databases was performed for randomized controlled trials (RCTs) comparing RFA plus biliary stent (RFA+S) versus biliary stent alone (S-alone). Outcomes assessed included overall survival, stent patency, and adverse events (AEs) with mean difference (MD) calculated from pooled proportions. Subgroup analyses were performed for hilar strictures and cholangiocarcinoma (CCA). Results Six RCTs (n=439 patients) were included and demonstrated improved survival among patients who received RFA+S (MD 85.80 days; 95% confidence interval [CI] 35.02-136.58; I 2 =97%; P <0.0009). The pooled MD for total stent patency was 22.25 days (95% CI 17.38-61.87; I 2 =97%; P =0.27). There was no difference in AEs between RFA+S vs S-alone ( P >0.05). On subgroup analyses, RFA+S was associated with improved stent patency (MD 76.73 days; 95% CI 50.11-103.34; I 2 =67%; P <0.01) and OS (MD 83.14 (95% CI 29.52-136.77; I 2 =97%; P <0.01] for CCA. For hilar strictures, stent patency was improved among patients with RFA+S [MD 83.71 days (95% CI 24.85-142.56; I 2 =84%; P <0.01]. Conclusions RFA+S improved OS in the treatment of MBO when compared with S-alone. Moreover, the RFA therapy prolonged stent patency in hilar strictures and CCA, with similar rates of AEs.

Computed tomography-based prediction of pancreatitis following biliary metal stent placement with the convolutional neural network.

Background and study aims Pancreatitis is a potentially lethal adverse event of endoscopic transpapillary placement of a self-expandable metal stent (SEMS) for malignant biliary obstruction (MBO). Deep learning-based image recognition has not been investigated in predicting pancreatitis in this setting. Patients and methods We included 70 patients who underwent endoscopic placement of a SEMS for nonresectable distal MBO. We constructed a convolutional neural network (CNN) model for pancreatitis prediction using a series of pre-procedure computed tomography images covering the whole pancreas (≥ 120,960 augmented images in total). We examined the additional effects of the CNN-based probabilities on the following machine learning models based on clinical parameters: logistic regression, support vector machine with a linear or RBF kernel, random forest classifier, and gradient boosting classifier. Model performance was assessed based on the area under the curve (AUC) in the receiver operating characteristic analysis, positive predictive value (PPV), accuracy, and specificity. Results The CNN model was associated with moderate levels of performance metrics: AUC, 0.67; PPV, 0.45; accuracy, 0.66; and specificity, 0.63. When added to the machine learning models, the CNN-based probabilities increased the performance metrics. The logistic regression model with the CNN-based probabilities had an AUC of 0.74, PPV of 0.85, accuracy of 0.83, and specificity of 0.96, compared with 0.72, 0.78, 0.77, and 0.96, respectively, without the probabilities. Conclusions The CNN-based model may increase predictability for pancreatitis following endoscopic placement of a biliary SEMS. Our findings support the potential of deep learning technology to improve prognostic models in pancreatobiliary therapeutic endoscopy.

Pure cut vs. Endocut in endoscopic biliary sphincterotomy: Systematic review and meta-analysis of randomized clinical trials.

Background and study aims Biliary sphincterotomy is a crucial step in endoscopic retrograde cholangiopancreatography (ERCP), a procedure known to carry a 5% to 10% risk of complications. The relationship between Pure cut, Endocut, post-ERCP pancreatitis (PEP) and bleeding is unclear. This systematic review and meta-analysis compared these two current types and their relationships with adverse events. Patients and methods This systematic review involved searching articles in multiple databases until August 2023 comparing pure cut versus Endocut in biliary sphincterotomy. The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Results A total of 987 patients from four randomized controlled trials were included. Overall pancreatitis: A higher risk of pancreatitis was found in the Endocut group than in the Pure cut group ( P =0.001, RD=0.04 [range, 0.01 to 0.06]; I 2 =29%). Overall immediate bleeding: Statistical significance was found to favor Endocut, ( P =0.05; RD=-0.15 [range, -0.29 to -0.00]; I 2 =93%). No statistical significance between current modes was found in immediate bleeding without endoscopic intervention ( P =0.10; RD=-0.13 [range, -0.29 to 0.02]; I 2 =88%), immediate bleeding with endoscopic intervention ( P =0.06; RD=-0.07 [range, -0.14 to 0.00]; I 2 =76%), delayed bleeding (P=0.40; RD=0.01 [range, -0.02 to 0.05]; I 2 =72%), zipper cut ( P =0.58; RD=-0.03 [range, -0.16 to 0.09]; I 2 =97%), perforation ( P =1.00; RD=0.00 [range, -0.01 to 0.01]; I 2 =0%) and cholangitis ( P =0.77; RD=0.00 [range, -0.01 to 0.02]; I 2 =29%). Conclusions The available data in the literature show that Endocut carries an increased risk for PEP and does not prevent delayed or clinically significant bleeding, although it prevents intraprocedural bleeding. Based on such findings, Pure cut should be the preferred electric current mode for biliary sphincterotomy.

Impact of temperature-controlled endobiliary radiofrequency ablation for inoperable hilar cholangiocarcinoma: A propensity score-matched analysis.

Background and study aims Endobiliary radiofrequency ablation (RFA) can be an effective palliative treatment, but few studies have evaluated its outcomes for malignant obstruction in the hilar bile duct, which has a thin wall and complex duct-vascular contacts. We evaluated the efficacy and safety of temperature-controlled endobiliary RFA, which can reduce the risk of unintentional thermal injury by maintaining the temperature of the ablation segment, in the treatment of inoperable hilar cholangiocarcinoma (CCA). Patients and methods After propensity score matching, 64 patients with inoperable hilar CCA were categorized to the RFA + stent group (endobiliary RFA with stenting; n=32) or stent-only group (stenting only; n=32). The evaluated outcomes were the median time to recurrent biliary obstruction (RBO), overall survival (OS), and adverse events (AEs). Results Technical success was achieved in all patients. The clinical success rate was 93.8% in the RFA + stent group and 87.5% in the stent-only group ( P =0.672). The median time to RBO was 242 days in the RFA + stent group and 168 days in the stent-only group ( P =0.031). The median OS showed a non-significant tendency to be higher in the RFA + stent group (337 versus 296 days; P =0.260). Overall AE rates were comparable between the two groups (12.5% vs 9.4%, P =1.000). Conclusions Temperature-controlled endobiliary RFA resulted in favorable stent patency without increasing the rate of AEs but it did not significantly increase OS in patients with inoperable hilar CCA (Clinical trial registration number: KCT0008576).

Assessment of pancreatic ductal stone density on non-contrast computed tomography for predicting the outcome of extracorporeal shock wave lithotripsy.

Background and study aims The utility of stone density at non-contrast computed tomography (NCCT) for predicting the effectiveness of extracorporeal shock wave lithotripsy (ESWL) in chronic calcific pancreatitis (CCP) is relatively unexplored. Patients and methods This was a prospective observational study of patients with CCP. Hounsfield units (HU) were determined for the largest pancreatic ductal stone during pretreatment NCCT. All patients underwent ESWL until the largest stone was fragmented to <3mm, followed by endoscopic retrograde cholangiopancreatography (ERCP) for stone extraction. The predictive factors following ESWL for successful stone extraction were studied and the receiver operating characteristic (ROC) curve determined the HU optimal cut-point. Results Eighty-two patients with a median (interquartile range) age of 36 years (range, 29-55); majority male 45 (54.9%), were included. Idiopathic CCP was noted in 78 patients (95.1%). The median stone density (SD) was 1095 HU (range, 860.7-1260.7) and the number of ESWL sessions was 2 (range, 2-3). Complete stone removal at index ERCP was achieved in 55 patients (67.1%). Those with partial clearance (n=27) needed a repeat ERCP, which was successful in 26 (96.3%); one patient (3.7%) underwent surgery. There was a significant, positive correlation between number of ESWL sessions and SD (r=0.797; P <0.001). On bivariate analysis, SD and the number of ESWL sessions revealed a significant association with complete ductal clearance. The optimal cut-point for complete stone removal by the ROC curve was 1106.5 HU (Youden index 0.726), with a sensitivity of 93% and a specificity of 80%. Conclusions The SD is a significant predictor of ESWL success followed by ductal clearance at ERCP, and <1106.5 HU is a predictor of good candidates for ESWL therapy.

Feasibility and safety of a novel plastic stent designed specifically for endoscopic ultrasound-guided pancreatic duct drainage.

Background and study aims Endoscopic ultrasound-guided pancreatic duct drainage (EUS-PD) is emerging as an effective alternative treatment for obstructive pancreatitis after unsuccessful endoscopic retrograde pancreatography (ERP). However, the high incidence of adverse events associated with EUS-PD (approximately 20%) remains an issue. Recently, we developed a novel plastic stent for EUS-PD, with a radiopaque marker positioned at approximately one-third of the length from the distal end of the stent and side holes positioned exclusively distal to the marker. This study aimed to evaluate the feasibility and safety of using this stent in EUS-PD. Patients and methods We retrospectively reviewed data from 10 patients who underwent EUS-PD with the novel plastic stent at the National Cancer Center Hospital between March 2021 and October 2023. Technical and clinical success, procedure times, adverse events (AEs), recurrent pancreatic duct obstruction (RPO), and time to RPO were assessed. Results Of the 10 patients, five had postoperative benign pancreaticojejunal anastomotic strictures and five had malignant pancreatic duct obstruction. The technical and clinical success rates were both 100% (10/10). An AE (self-limited abdominal pain) occurred in one patient (10.0%). Two patients (20.0%) died of their primary disease during the follow-up period (median, 44 days; range, 25-272 days). The incidence of RPO was 10.0% (1/10), and the 3-month non-RPO rate was 83.3%. Conclusions The novel plastic stent shows potential as a useful and safe tool in EUS-PD.

Primary anastomosis closure after endoscopic ultrasound-directed transgastric intervention.

Background and study aims Endoscopic ultrasound-directed transgastric intervention (EDGI) is a technique that creates an anastomosis between the gastric pouch or jejunum to the excluded stomach in Roux-en-Y gastric bypass (RYGB) anatomy to allow access to the pancreaticobiliary system. Thus far, management of anastomosis closure at the time of lumen-apposing metal stent (LAMS) removal has varied widely. This study aimed to assess the efficacy of primary closure at the time of LAMS removal using a through-the-scope (TTS) tack-based suture system.  Patients and methods This was a two-center retrospective study of RYGB patients who underwent single-stage EDGI using a 20-mm LAMS and subsequent primary anastomosis closure with the X-tack system at the time of stent removal. Patient demographics, procedure details, clinical outcomes, and imaging findings are reported. Results Nineteen patients (median age 63 years, 84% female) underwent single-stage EDGI with a median follow-up of 31.5 months. Adverse events occurred in two patients (11%) who had abdominal pain requiring hospitalization. The median LAMS dwell time was 32 days (range 16-86). All patients (100%) who underwent follow-up studies after LAMS removal had confirmed anastomosis closure (n = 18). Most patients had documented weight loss at the time of LAMS removal and at last follow-up (68%, n = 13). Conclusions Single-stage EDGI is an effective approach to managing RYGB patients with pancreaticobiliary pathology. Thus far, endoscopic TTS tack-based suturing appears to have a high success rate in anastomosis closure after LAMS removal and should be considered as a primary method for preventing chronic fistulae.

Impact of a new dedicated sheath device for tissue sampling of biliary stricture on pathological diagnostic yield: Retrospective study.

Background and study aims Endoscopic transpapillary biliary forceps biopsy (TBFB) is a common method for obtaining specimens from biliary lesions. Its diagnostic yield is unsatisfactory; to overcome this disadvantage, a dedicated sheath has been developed. This study aimed to evaluate the outcomes of conventional TBFB and TBFB with a novel sheath device. Patients and methods Consecutive patients who underwent TBFB between January 2020 and December 2021 were retrospectively evaluated. The rate of obtaining adequate samples, failed attempts at forceps insertion into the bile duct, and sensitivity were compared between the two groups. Results Ninety-two patients who underwent 115 endoscopic retrograde cholangiopancreatographies (76 in the conventional group vs. 39 in the dedicated sheath group) were included. The rates of obtaining adequate samples, failed attempts of the forceps into the bile duct, and sensitivity were 72.4% vs. 89.7% ( P = 0.03), 28.3% vs. 0% ( P < 0.01), and 66.7% vs. 88.9% ( P = 0.02), respectively. Conclusions TBFB with the novel sheath device contributed to improved sensitivity for diagnosis of biliary stricture without insertion of forceps outside the bile duct.

Accurate and safe diagnosis and treatment of neoplastic biliary lesions using a novel 9F and 11F digital single-operator cholangioscope.

Background and study aims Digital single-operator cholangioscopy (DSOC) allows the diagnosis of biliary duct disorders and treatment for complicated stones. However, these technologies have limitations such as the size of the probe and working channel, excessive cost, and low image resolution. Recently, a novel DSOC system (eyeMAX, Micro-Tech, Nanjing, China) was developed to address these limitations. We aimed to evaluate the usefulness and safety of a novel 9F and 11F DSOC system in terms of neoplastic diagnostic accuracy based on visual examination, ability to evaluate tumor extension and to achieve complete biliary stone clearance, and procedure-related adverse events (AEs). Patients and methods Data from ≥ 18-year-old patients who underwent DSOC from July 2021 to April 2022 were retrospectively recovered and divided into a diagnostic and a therapeutic cohort. Results A total of 80 patients were included. In the diagnostic cohort (n = 49/80), neovascularity was identified in 26 of 49 patients (46.9%). Biopsy was performed in 65.3% patients with adequate tissue sample obtained in 96.8% of cases. Biopsy confirmed neoplasia in 23 of 32 cases. DSOC visual impression achieved 91.6% sensitivity and 87.5% specificity in diagnosing neoplasms. In the therapeutic cohort (n = 43/80), 26 of 43 patients required lithotripsy alone. Total stone removal was achieved in 71% patients in the first session. Neither early nor late AEs were documented in either the diagnostic or therapeutic cohort. Conclusions The novel DSOC device has excellent diagnostic accuracy in distinguishing neoplastic biliary lesions as well as therapeutic benefits in the context of total stone removal, with no documented AEs.

Outcomes predictors in endoscopic ultrasound-guided choledochoduodenostomy with lumen-apposing metal stent: Systematic review and meta-analysis.

Background and study aims EUS-guided choledochoduodenostomy (EUS-CDS) is a minimally invasive procedure used to treat malignant biliary obstruction (MBO) by transduodenal placement of a lumen-apposing metal stent (LAMS) into the extrahepatic bile duct. To identify factors that contribute to safe and effective EUS-CDS using LAMS, we performed a systematic review of the literature and meta-analysis. Methods The methodology of our analysis was based on PRISMA recommendations. Electronic databases (Medline, Scopus, EMBASE) were searched up to November 2022. Full articles that included patients with distal malignant biliary obstruction who underwent EUS-CDS using LAMS after failed endoscopic retrograde cholangiopancreatography were eligible. Random-effect meta-analysis was performed reporting pooled rates of technical success, clinical success, and adverse events (AEs) by means of a random model. Multivariate meta-regression and subgroup analysis were performed to assess possible associations between the outcomes and selected variables to assess the correlation between outcomes and different variables. Results were also stratified according to stent size. Results Twelve studies with 845 patients were included in the meta-analysis. Pooled technical and clinical success rates were 96% (95% confidence interval [CI] 94%-98%; I 2 = 52.29%) and 96% (95%CI 95%-98%), respectively, with no significant association with baseline characteristics, such are sex, age, common bile duct diameter, or stent size. The pooled AE rate was 12% (95%CI: 8%-16%; I 2 = 71.62%). The AE rate was significantly lower when using an 8 × 8 mm stent as compared with a 6 × 8 mm LAMS (odds ratio 0.59, 0.35-0.99; P = 0.04), with no evidence of heterogeneity (I 2 = 0%). Conclusions EUS-CDS with LAMS is a safe and effective option for relief of MBO. Selecting an appropriate stent size is crucial for achieving optimal safety outcomes.

Association of short-course antimicrobial therapy and bacterial resistance in acute cholangitis: Retrospective cohort study.

Background and study aims Although the number of resistant bacteria tends to increase with prolonged antimicrobial therapy, no studies have examined the relationship between the duration of antimicrobial therapy and increase in the number of resistant bacteria in acute cholangitis. We hypothesized that the short-term administration of antimicrobial agents in acute cholangitis would suppress bacterial resistance. Patients and methods This was a single-center, retrospective, observational study of patients with acute cholangitis admitted between January 2018 and June 2020 who met the following criteria: successful biliary drainage, positive blood or bile cultures, bacteria identified from cultures sensitive to antimicrobials, and subsequent cholangitis recurrence by January 2022. The patients were divided into two groups: those whose causative organisms at the time of recurrence became resistant to the antimicrobial agents used at the time of initial admission (resistant group) and those who remained susceptible (susceptible group). Multivariate analysis was used to examine risk factors associated with the development of resistant pathogens. Multivariate analysis investigated antibiotics used with the length of 3 days or shorter after endoscopic retrograde cholangiopancreatography (ERCP) and previously reported risk factors for the development of bacterial resistance. Results In total, 89 eligible patients were included in this study. There were no significant differences in patient background or ERCP findings between the groups. The use of antibiotics, completed within 3 days after ERCP, was associated with a lower risk of developing bacterial resistance (odds ratio, 0.17; 95% confidence interval, 0.04-0.65; P =0.01). Conclusions In acute cholangitis, the administration of antimicrobials within 3 days of ERCP may suppress the development of resistant bacteria.

Evaluation of exclusive internal endoscopic drainage for complex biloma with transluminal and transpapillary stenting.

Background and study aims Biloma is treated endoscopically with endoscopic retrograde cholangiography (ERCP) or endoscopi ultrasound-guided transluminal biloma drainage (EUS-TBD). However, almost all previous studies have used both internal and external drainage. External drainage has the disadvantages of poor cosmetic appearance and self-tube removal. The aim of the present study was to evaluate the internal endoscopic drainage for complex biloma after hepatobiliary surgery with an ERCP- or EUS-guided approach, without external drainage. Patients and methods This retrospective study included consecutive patients who had bilomas. A 7F plastic stent was deployed from the biloma to the duodenum in the ERCP group and the metal stent was deployed from the biloma to the stomach in the EUS-TBD group. Results Forty-seven patients were enrolled. The technical success rate was similar between the groups (ERCP 94% vs EUS-TBD 100%, P =0.371); however, mean procedure time was significantly shorter in the EUS-TBD group (16.9 minutes) than in the ERCP group (26.6 minutes) ( P =0.009). The clinical success rate was 87% (25 of 32 patients) in the ERCP group and 84% (11 of 13 patients) in the EUS-TBD group ( P =0.482). The duration of median hospital stay was significantly shorter in the EUS-TBD group (22 days) than in the ERCP group (46 days) ( P =0.038). There was no significant difference in procedure-associated adverse events between the groups. Conclusions In conclusion, ERCP and EUS-TBD are complementary techniques, each with its own merits in specific clinical scenarios. If both techniques can be performed, EUS-TBD should be considered because of the short times for the procedure, hospital stay. and biloma resolution.

Using a customized GPT to provide guideline-based recommendations for management of pancreatic cystic lesions.

Background and study aims Rising prevalence of pancreatic cysts and inconsistent management guidelines necessitate innovative approaches. New features of large language models (LLMs), namely custom GPT creation, provided by ChatGPT can be utilized to integrate multiple guidelines and settle inconsistencies. Methods A custom GPT was developed to provide guideline-based management advice for pancreatic cysts. Sixty clinical scenarios were evaluated by both the custom GPT and gastroenterology experts. A consensus was reached between experts and review of guidelines and the accuracy of recommendations provided by the custom GPT was evaluated and compared with experts. Results The custom GPT aligned with expert recommendations in 87% of scenarios. Initial expert recommendations were correct in 97% and 87% of cases, respectively. No significant difference was observed between the accuracy of custom GPT and the experts. Agreement analysis using Cohen's and Fleiss' Kappa coefficients indicated consistency among experts and the custom GPT. Conclusions This proof-of-concept study shows the custom GPT's potential to provide accurate, guideline-based recommendations for pancreatic cyst management, comparable to expert opinions. The study highlights the role of advanced features of LLMs in enhancing clinical decision-making in fields with significant practice variability.

Comparison of stent patency between EUS-guided hepaticogastrostomy with bridging and endoscopic transpapillary biliary drainage for hilar obstruction.

Background and study aims Endoscopic ultrasound-guided hepaticogastrostomy with bridging between the left and right bile ducts is an alternative to endoscopic transpapillary drainage for malignant hilar biliary obstruction. We aimed to analyze the long-term stent patency of endoscopic ultrasound-guided hepaticogastrostomy with bridging. Patients and methods Patients who underwent endoscopic ultrasound-guided hepaticogastrostomy with bridging between April 2018 and July 2023 were retrospectively analyzed. We retrospectively compared the stent patency of these patients with that of the individuals who underwent endoscopic transpapillary drainage-multi-stenting using unmatched (entire) and propensity score-matched cohorts. Results Endoscopic ultrasound-guided hepaticogastrostomy with bridging had a technical success rate of 90% (18/20). Adverse events were minimal. The number of clinical success cases was 17 and 82 for endoscopic ultrasound-guided hepaticogastrostomy with bridging using metallic stent and endoscopic transpapillary drainage-multi-stenting, respectively. The recurrent biliary obstruction rate was 17.6% and 58.5% for endoscopic ultrasound-guided hepaticogastrostomy with bridging and endoscopic transpapillary drainage-multi-stenting, respectively; the median time to recurrent biliary obstruction (days) was significantly longer for endoscopic ultrasound-guided hepaticogastrostomy with bridging in the entire (not reached vs. 104, P =0.03) and propensity score-matched (183 vs. 79, P =0.05) cohorts. The non-recurrent biliary obstruction rate for endoscopic ultrasound-guided hepaticogastrostomy with bridging was 91.6% at 3 and 6 months and 57% at 12 months. Multivariate analyses revealed that endoscopic ultrasound-guided hepaticogastrostomy with bridging contributed to a lower recurrent biliary obstruction incidence (hazard ratio, 0.31, P =0.05) without significant difference. Conclusions Stent patency was significantly better for endoscopic ultrasound-guided hepaticogastrostomy with bridging. However, future prospective studies are needed.

Novel treatment with double scope technique for disconnected pancreatic duct syndrome with external pancreatic fistula.

Background and study aims External pancreatic fistula in association with disconnected pancreatic duct syndrome is a common sequelae of the percutaneous step-up approach for infected pancreatic necrosis and is associated with significant morbidity. The present study aimed to report the initial outcome of a novel technique of two-scope guided tractogastrostomy for management of this condition. Patients and methods The present study was a retrospective analysis of data from patients with external pancreatic fistula and disconnected pancreatic duct syndrome, who underwent two-scope-guided tractogastrostomy. All the patients had a 24F or larger drain placed in the left retroperitoneum. Transgastric echo endoscopy and sinus tract endoscopy were performed simultaneously to place a stent between the gastric lumen and the sinus tract. Technical success was defined as placement of the stent between the tract and the stomach. Clinical success was defined as successful removal of the percutaneous drain without the occurrence of pancreatic fluid collection, ascites, external fistula, or another intervention 12 weeks after the procedure. Results Three patients underwent two scope-guided tractogastrostomy. Technical and clinical success were achieved in all the patients. No procedure-related side effects or recurrence occurred in any of the patients. Conclusions Two-scope-guided tractogastrostomy for treatment of external pancreatic fistula due to disconnected pancreatic duct syndrome is a feasible technique and can be further evaluated.