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Background/objectivesGermline genetic testing is recommended for younger patients with idiopathic pancreatitis but there has been a lack of consensus in recommendations for those over age 35. We aimed to analyze the results of genetic testing among subjects of varying ages.MethodsIndividuals who underwent germline multigene testing for pancreatitis susceptibility genes (CASR, CFTR, CPA1, CTRC, PRSS1, SPINK1) through a large commercial laboratory between 2017 and 2022 were included. Test results and information collected from test requisition forms were evaluated. Multivariable logistic regression models were performed to identify factors associated with a positive pancreatitis panel (pathogenic, likely pathogenic, and/or increased risk variants) in pancreatitis-related genes.ResultsOverall, 2,468 subjects with primary indication of acute pancreatitis (AP) (n = 401), chronic pancreatitis (CP) (n = 631), pancreatic cancer (n = 128), or other indications (n = 1,308) completed germline testing. Among patients with AP or CP, the prevalence of any positive result for those ConclusionsThe highest prevalence of pathogenic variants is seen in younger individuals with a positive family history of pancreatitis. However, clinically meaningful results are identified in older subjects, suggesting that genetic counseling and testing should be considered for all age groups.

Background and Objectives: While studies have demonstrated the efficacy of cholangioscopy-guided Holmium-Yttrium aluminum garnet (Ho:YAG) laser lithotripsy for the treatment of refractory bile duct stones, data regarding the safety of the operating parameters for laser lithotripsy are lacking. The aim of this study was to determine safe, yet effective, energy settings for Ho:YAG laser in the ex-vivo model. Materials and Methods: This ex vivo experimental study utilized the Ho:YAG laser on porcine bile duct epithelium and human gallstones. Ho:YAG laser lithotripsy was applied in different power settings from 8 to 15 Watts (W) to six explanted porcine bile ducts. Settings that appeared safe were then utilized to fragment seventy-three human gallstones. Results: The median bile duct perforation times with the Ho:YAG laser between 8–15 W were: >60 s (8 W); 23 s (9 W); 29 s (10 W); 27 s (12 W); 12 s (14 W); and 8 s (15 W). Statistically significant differences in the median perforation times were noted between 8 W vs. 15 W, 9 W vs. 15 W, 10 W vs. 15 W, and 12 W vs. 15 W (p < 0.05). When using a 365 µm Ho:YAG laser probe at 8–12 W, the fragmentation rates on various size stones were: 100% (2.0 cm). Optimal fragmentation was seen utilizing 12 W with high energy (2.4 J) and low frequency (5 Hz) settings. Using a larger 550 µm probe at these settings resulted in 100% fragmentation of stones larger than 2 cm. Conclusions: The Ho:YAG laser appears to be safe and effective in the treatment of large bile duct stones when used between 8–12 W in 5 s bursts in an ex vivo model utilizing porcine bile ducts and human gallstones.

Purpose: To investigate the clinical response to infliximab in ocular inflammation patients who develop anti-infliximab antibodies (AIA) vs. those patients who do not develop AIA. Observations: A retrospective review was performed of patients treated with infliximab for noninfectious uveitis (NIU) or scleritis. Clinical response was determined as a composite clinical endpoint and classified as complete, partial, or absent. Nine of 32 infliximab-treated patients (28%) were found to develop AIA. Among the AIA-positive patients, clinical response was complete in 7 patients (78%) and partial in 2 patients (22%). Among the AIA-negative patients, clinical response was complete in 15 patients (65%), partial in 6 patients (26%) and absent in 2 patients (9%). Serum infliximab levels tended to decrease with appearance of AIA but rarely became undetectable. Conclusions and Importance: In this pilot study, AIA-positive patients did not have diminished clinical response to infliximab when compared with AIA-negative patients. There was a high rate of complete clinical response to infliximab in this group of NIU and scleritis patients. Approximately a quarter of patients developed AIA. AIA-positive patients did not have diminished rates of clinical response when compared with AIA-negative patients. This suggests that routine AIA monitoring may not be clinically useful, although validation of this finding in larger cohorts is necessary.

Background and study aims Dominant strictures (DS) occur in up to 60 % of patients with primary sclerosing cholangitis (PSC). Data regarding the long-term effects of stenting vs. dilation remain limited. The aim of this study was to compare the two treatment modalities in terms of transplantation-free survival. Patients and methods This single-center, retrospective study examined patients with PSC and DS treated endoscopically with a minimum of 1 year follow-up. Patients were divided into two cohorts: 1) those who received dilation alone; and 2) those who received both dilation and stenting. The primary outcome was transplantation-free survival, defined as time after index ERCP to liver transplantation. Results In all, 169 patients (54 in dilation cohort, 115 in stenting cohort) were included. The stenting cohort had a significantly higher Mayo PSC Risk Score (1.8 ± 1.1 vs. 0.9 ± 1.2) and presented with cholangitis more frequently (22.6 % vs. 1.9 %). During a follow-up period of 1198 person-years, 69 (40.8 %) patients received transplantation at a mean of 3.4 (± 2.9) years. There was no difference in transplantation rate in the stenting cohort [68 (95 % CI 5.2–8.8) per 100 person-years] compared to the dilation cohort [3.7 (95 % CI 2.1–6.0) per 100 person-years] and no difference in risk for transplantation (dilation cohort adjusted hazards ratio 0.67, 95 % CI 0.33–1.32). Conclusions Despite a higher Mayo Risk Score in the stenting group, there was no difference in transplantation-free survival between patients managed with stenting vs. dilation alone. Stenting, therefore, may offer benefit in patients with advanced PSC and DS.

Choroidal caverns (CCs) have been described in association with age-related macular degeneration and pachychoroid disease. However, it is unknown if caverns are found in patients with chronic non-infectious uveitis (NIU). Herein, we evaluated patients with NIU who had optical coherence tomography and indocyanine green angiography for CCs. Clinical and demographic characteristics were extracted from the chart review. Univariate and multivariate mixed-effects logistical models were used to assess the association between clinical and demographic factors and the presence of CCs. One hundred thirty-five patients (251 eyes) met the inclusion criteria: 1 eye had anterior uveitis, 5 had intermediate uveitis, 194 had posterior uveitis, and 51 had panuveitis. The prevalence of CCs was 10%. CCs were only observed in patients with posterior and panuveitis, with a prevalence of 10.8% and 7.8%, respectively. Multifocal choroiditis (MFC) was the type of uveitis where CCs were most frequently observed, with 40% of eyes with MFC having CCs. In addition, male sex (p = 0.024) was associated with CCs. There was no significant difference in the degree of intraocular inflammation or mean subfoveal choroidal thickness between CC+ and CC− eyes. This is the first study to describe CCs in uveitis. Overall, these findings suggest that caverns may be a sequela of structural and/or vascular perturbations in the choroid from uveitis.

Background and study aims Hands-on training for per-oral endoscopic myotomy (POEM) in the United States is limited and without a structured curriculum or assessment tool. Training to competency in POEM is critical and POEM trainees must acquire multiple cognitive and technical skills to achieve proficiency. The aim of this study was to develop a POEM training and skills evaluation tool. Patients and methods The training protocol included initial explant porcine models followed by live human cases, proctored by a single endoscopist experienced in POEM who prospectively graded trainees for each step (“skill”) of the procedure on a 5-point scale. Procedural skills were divided into cognitive and technical skills. Acceptable passing level was considered a score ≥ 4 for each skill. Results Three trainees completed a total of 18 cases (8 cases on animal explant models and 10 human cases). Overall, cognitive skills were acquired early in training with scores of ≥ 4 achieved by ≤ 3 cases. Technical skills required more cases and direction with scores ≥ 4 in technical skills achieved by three porcine and eight human cases. Entry of the endoscope into the submucosal space and submucosal tunneling were the most challenging steps followed by myotomy. Conclusion This pilot study introduces a POEM training and skills evaluation tool for training to competency. Submucosal entry, tunneling, and myotomy were the most challenging to learn while cognitive skills were learned early in training. Evaluation of more trainees at multiple sites will be necessary to further validate the utility of this tool.

Background and study aims Third space endoscopy (TSE), including per-oral endoscopic myotomy and endoscopic submucosal dissection, is technically challenging and physically demanding. The aim of this study was to assess the prevalence and types of musculoskeletal symptoms and injuries (MSI) in third space endoscopists and its impact on clinical practice. Materials, Patients and methods A 22-item survey measuring endoscopist characteristics, procedure volumes, MSI, and its effect on clinical practice was distributed to endoscopists practicing TSE. Descriptive statistics were used to depict MSI. Logistic regression was used to identify predictors for MSI related to TSE. Results The survey was completed by 45 of 110 endoscopists (40.9 %) who received the survey, representing 10 countries across four continents. Thirty-one (69 %) endoscopists reported current MSI with 71 % (n = 22/31) believing these began after starting TSE, and 48.9 % (22/45) reporting more symptoms after TSE compared to endoscopic ultrasound/endoscopic retrograde cholangiopancreatography. Common MSI included the shoulders (42.2 %), back (37.8 %), neck (33.3 %), and wrist (24.4 %). Lower extremity MSI were also reported with foot symptoms (11.1 %) being most common. A minority required disability (2.2 %), change in endoscopy scheduling (6.7 %) or surgery (2.2 %). Only 15.6 % of endoscopists had received prior ergonomics training. Logistic regression revealed no significant predictors for MSI. Conclusions Over two-thirds of endoscopists performing TSE suffer from MSI, with many reporting onset of their symptoms after starting TSE in their practice. Further studies are needed to understand and reduce the risk of MSI in TSE given the growing demand for these procedures and the potential long-term impact of this occupational hazard.

Background and study aim Endoscopic submucosal dissection (ESD) enables en bloc removal of gastrointestinal epithelial lesions but can leave a large mucosal defect, which can lead to inpatient observation and delayed bleeding or perforation. The aim of this study was to examine the safety and effectiveness of endoscopic suturing in closing ESD defects to prevent adverse events. Patients and methods In this single-center prospective cohort study, endoscopic suturing was performed to close ESD defects in the stomach or rectum. Suturing was performed in the antegrade position starting from the edge most distal to the endoscope insertion site, moving from right to left, left to right manner before ending at the edge most proximal to the endoscope insertion site. Results In total, 31 patients (mean age 65.6, 71 % male) received endoscopic suturing after gastric (58.1 %) or rectal (41.9 %) ESD. Mean lesion size was 27.4 ± 16.2 mm and mean suturing time was 13.4 ± 5.9 min. Complete closure was achieved in all patients. Same-day discharge occurred in 58.1 % of patients; the remainder were hospitalized with mean length of stay of 1 ± 0.6 day. There were no instances of delayed bleeding or delayed perforation (0 %, 95 % CI: 0–11.5 %). No recurrences were found on surveillance endoscopy. Conclusions Based on this small prospective study, endoscopic suturing of post-ESD defects in the stomach and rectum appears to be feasible, safe, and potentially effective in preventing bleeding or perforation. Further larger controlled studies, however, are needed to validate these findings.

Background and study aims Cholangiopancreatoscopy-guided laser dissection or ablation (CPL) is a novel therapeutic modality for refractory benign strictures. Our aim was to describe the safety and efficacy of CPL for pancreaticobiliary disorders. Patients and methods Patients who underwent CPL using holmium or thulium laser between February 2017 and September 2019 were included. For stricture dissection, gentle strokes of the laser fiber from a distal to proximal approach were applied until luminal patency permitted advancement of the cholangiopancreatoscope. Immediate technical success was defined as ability to traverse the stricture with the cholangiopancreatoscope after CPL. Short-term technical success was defined as > 90 % resolution of the stricture on follow-up pancreatogram. Results Eleven patients underwent a mean of 3.6 ERCPs (mean total diameter of 14.2 Fr of stenting) prior to CPL. Indications included pancreatic duct stricture (n = 8), pancreaticojejunostomy anastomotic stricture (n = 1), bile duct stricture (n = 1) and pancreatic intraductal papillary mucinous neoplasm ablation (n = 1). Immediate technical success was 94.1 % and short-term technical success rates was 88.2 %. At a mean follow-up of 12.1 months, there have been no stricture recurrences. Conclusions CPL may be an effective therapy for strictures refractory to conventional dilation and multiple stenting.

The push for high quality care in all fields of medicine highlights the importance of establishing and adhering to quality indicators. In response, several gastrointestinal societies have established quality indicators specific to Barrett’s esophagus, which serve to create thresholds for performance while standardizing practice and guiding value-based care. Recent studies, however, have consistently demonstrated the lack of adherence to these quality indicators, particularly in surveillance (appropriate utilization of endoscopy and obtaining biopsies using the Seattle protocol) and endoscopic eradication therapy practices. These findings suggest that innovative interventions are needed to address these shortcomings in order to deliver high quality care to patients with Barrett’s esophagus.

Background and study aims The role of the digital single-operator pancreatoscopy (D-SOP) with electrohydraulic (EHL) or laser lithotripsy (LL) in treating pancreatic ductal stones is unclear. We investigated the safety and efficacy of D-SOP with EHL or LL in patients with obstructing pancreatic duct stones. Patients and methods Retrospective analysis of 109 patients who underwent D-SOP for pancreatic stones at 17 tertiary centers in the United States and Europe from February 2015 to September 2017. Logistic regression was performed to identify factors associated with the need for more than one D-SOP with EHL/LL. Results Most patients were males (70.6 %),mean age 54.7 years. Fifty-nine (54.1 %) underwent EHL and 50 (45.9 %) underwent LL. Mean procedure time was longer in the EHL group (74.4 min vs 53.8 min; P

Novel binary gene expression tools like the LexA-LexAop system could powerfully enhance studies of metabolism, development, and neurobiology in Drosophila. However, specific LexA drivers for neuroendocrine cells and many other developmentally relevant systems remain limited. In a unique high school biology course, we generated a LexA-based enhancer trap collection by transposon mobilization. The initial collection provides a source of novel LexA-based elements that permit targeted gene expression in the corpora cardiaca, cells central for metabolic homeostasis, and other neuroendocrine cell types. The collection further contains specific LexA drivers for stem cells and other enteric cells in the gut, and other developmentally relevant tissue types. We provide detailed analysis of nearly 100 new LexA lines, including molecular mapping of insertions, description of enhancer-driven reporter expression in larval tissues, and adult neuroendocrine cells, comparison with established enhancer trap collections and tissue specific RNAseq. Generation of this open-resource LexA collection facilitates neuroendocrine and developmental biology investigations, and shows how empowering secondary school science can achieve research and educational goals.

Background and study aims: Retrograde double-balloon enteroscopy (RDBE) has a high failure rate due to difficulty intubating the ileo-cecal (IC) valve. We examined the utility of a pre-RDBE colonoscopy using a pediatric colonoscope to clean the cecum and perform an initial intubation of the IC valve. Patients and methods: This study is a retrospective review of RDBE procedures for 45 patients at a single tertiary-care center to examine the success of IC intubation, maximal depth of enteroscope insertion, and duration of the procedure. Results: The IC intubation success rate among patients who underwent RDBE using this novel method was 100 % as compared to 72.7 % using the traditional method (P

Abstract Drawing inspiration from cohesive integration of skeletal muscles and sensory skins in vertebrate animals, we present a design strategy of soft robots, primarily consisting of an electronic skin (e-skin) and an artificial muscle. These robots integrate multifunctional sensing and on-demand actuation into a biocompatible platform using an in-situ solution-based method. They feature biomimetic designs that enable adaptive motions and stress-free contact with tissues, supported by a battery-free wireless module for untethered operation. Demonstrations range from a robotic cuff for detecting blood pressure, to a robotic gripper for tracking bladder volume, an ingestible robot for pH sensing and on-site drug delivery, and a robotic patch for quantifying cardiac function and delivering electrotherapy, highlighting the application versatilities and potentials of the bio-inspired soft robots. Our designs establish a universal strategy with a broad range of sensing and responsive materials, to form integrated soft robots for medical technology and beyond.