Utility of methylated DNA markers for the diagnosis of malignant biliary strictures.

BACKGROUND AND AIMS: Early identification of malignant biliary strictures (MBS) is challenging, with up to 20% classified as indeterminants after preliminary testing and tissue sampling with endoscopic retrograde cholangiopancreatography (ERCP). We aimed to evaluate the use of methylated DNA markers (MDM) from biliary brushings to enhance MBS detection in a prospective cohort. METHODS: Candidate MDMs were evaluated for their utility in MBS diagnosis through a series of discovery and validation phases. DNA was extracted from biliary brushing samples, quantified, bisulfite-converted, and then subjected to methylation-specific Droplet Digital Polymerase Chain Reaction (ddPCR).  Patients were considered to have no malignancy if the sampling was negative and there was no evidence of malignancy after 1 year or definitive negative surgical histopathology. RESULTS: Fourteen candidate MDMs were evaluated in the discovery phase, with top-performing and new markers evaluated in the technical validation phase. The top four MDMs were TWIST1, HOXA1, VSTM2B, and CLEC11A, which individually achieved AUC values of 0.82, 0.81, 0.83, and 0.78, respectively, with sensitivities of 59.4%, 53.1%, 62.5%, and 50.0%, respectively, at high specificities for malignancy of 95.2-95.3% for the final biologic validation phase. When combined as a panel, the AUC was 0.86, achieving 73.4% sensitivity and 92.9% specificity, which outperformed cytology and fluorescent in situ hybridization (FISH). CONCLUSIONS: The selected methylated DNA markers demonstrated improved performance characteristics for the detection of MBS compared to cytology and FISH. ​ Therefore, MDMs should be considered viable candidates for inclusion in diagnostic testing algorithms.​.

Third and Fourth Vaccine Doses Broaden and Prolong Immunity to SARS-CoV-2 in Adult Patients with Immune-Mediated Inflammatory Diseases.

Previous studies have reported impaired humoral responses after SARS-CoV-2 mRNA vaccination in patients with immune-mediated inflammatory diseases (IMIDs), particularly those treated with anti-TNF biologics. We previously reported that IMID patients diagnosed with inflammatory bowel disease, psoriasis, psoriatic arthritis, ankylosing spondylitis, or rheumatoid arthritis exhibited greater waning of Ab and T cell responses than healthy control subjects after SARS-CoV-2 vaccine dose 2. Fewer data are available on the effects of third and fourth doses. This observational cohort study collected plasma and PBMCs from healthy control subjects and untreated or treated patients with IMIDs prevaccination and after one to four doses of SARS-CoV-2 mRNA vaccine (BNT162b2 or mRNA-1273). SARS-CoV-2-specific Ab levels, neutralization, and T cell cytokine release were measured against wild-type and Omicron BA.1 and BA.5 variants of concern. Third vaccine doses substantially restored and prolonged Ab and T cell responses in patients with IMIDs and broadened responses against variants of concern. Fourth-dose effects were subtle but also prolonged Ab responses. However, patients with IMIDs treated with anti-TNF, especially patients with inflammatory bowel disease, exhibited lower Ab responses even after the fourth dose. Although T cell IFN-γ responses were maximal after one dose, IL-2 and IL-4 production increased with successive doses, and early production of these cytokines was predictive of neutralization responses at 3-4 mo postvaccination. Our study demonstrates that third and fourth doses of the SARS-CoV-2 mRNA vaccines sustain and broaden immune responses to SARS-CoV-2, supporting the recommendation for three- and four-dose vaccination regimens in patients with IMIDs.

Valuing innovative endoscopic techniques: hemostatic powder for the treatment of GI tumor bleeding.

BACKGROUND AND AIMS: Access to new endoscopic treatment modalities often depends on price. To resolve this gap and therefore help to ensure that care delivery can occur on a clinical basis, we aimed to establish the value to insurers of novel hemostatic powder to treat GI tumor bleeding. METHODS: A decision-analytic model developed to assess the impact of endoscopic intervention on the risk of 30-day readmission for GI bleeding from an insurer perspective was adapted to assess GI tumor bleeding with hemostatic powder or standard endoscopic therapy. Costs were derived from Medicare populations. Outcomes were derived from a recent multicenter randomized clinical trial. RESULTS: Costs ranged from $651 to $1613 to treat upper GI tumor bleeding and from $531 to $1014 to treat lower GI tumor bleeding based on risk reduction in 30-day hospital readmission for recurrent bleeding. These valuations should represent medical device and incremental facility costs in addition to incremental physician and staff time. CONCLUSIONS: Coverage for novel endoscopic hemostatic powder therapy seems cost-saving to insurers.

Safety of EUS latex balloon use in patients with a latex allergy.

BACKGROUND AND AIMS: Balloons are used in EUS to improve visualization. However, data on the safety of latex balloons in patients with latex allergies are limited, and nonlatex alternatives can be costly. We investigated the safety of latex balloon use during EUS. METHODS: A retrospective review was conducted at a tertiary center between 2019 and 2022. Patients with reported latex allergies who underwent linear EUS were included. Baseline demographics, EUS characteristics, and adverse events were collected. The primary outcome was the rate of adverse events. RESULTS: Eighty-seven procedures were performed on 57 unique patients (mean age, 65.3 ± 14.5 years). Latex balloons were used in 59 procedures (67.8%), with only 8 procedures (13.6%) using prophylactic medications. No adverse events occurred during or after procedures, regardless of medication use or history of anaphylaxis. CONCLUSIONS: The use of EUS latex balloons in patients with a latex allergy was associated with no adverse events.

Development and initial validation of a video-based peroral endoscopic myotomy assessment tool.

BACKGROUND AND AIMS: Video analysis has emerged as a potential strategy for performance assessment and improvement. We aimed to develop a video-based skill assessment tool for peroral endoscopic myotomy (POEM). METHODS: POEM was deconstructed into basic procedural components through video analysis by an expert panel. A modified Delphi approach and 2 validation exercises were conducted to refine the POEM assessment tool (POEMAT). Twelve assessors used the final POEMAT version to grade 10 videos. Fully crossed generalizability (G) studies investigated the contributions of assessors, endoscopists' performance, and technical elements to reliability. G coefficients below .5 were considered unreliable, between .5 and .7 as modestly reliable, and above .7 as indicative of satisfactory reliability. RESULTS: After task deconstruction, discussions, and the modified Delphi process, the final POEMAT comprised 9 technical elements. G analysis showed low variance for endoscopist performance (.8%-24.9%) and high interrater variability (range, 63.2%-90.1%). The G score was moderately reliable (≥.60) for "submucosal tunneling" and "myotomy" and satisfactorily reliable (≥.70) for "active hemostasis" and "mucosal closure." CONCLUSIONS: We developed and established initial content and response process validity evidence for the POEMAT. Future steps include appraisal of the tool using a wider range of POEM videos to establish and improve the discriminative validity of this tool.

Lumen-apposing metal stents with or without coaxial plastic stent placement for the management of pancreatic fluid collections.

BACKGROUND AND AIMS: Coaxial double-pigtail plastic stent (DPPS) placement is often performed within lumen-apposing metal stents (LAMSs) for drainage of pancreatic fluid collections (PFCs) to prevent adverse events (AEs) such as stent occlusion and bleeding. This study compares the safety and outcomes of LAMSs alone versus LAMSs with coaxial DPPSs for PFC management. METHODS: Patients undergoing drainage of a PFC with LAMSs were retrospectively identified and categorized as LAMS or LAMS/DPPS based on initial drainage strategy. The AE rate, AE type, and clinical success were extracted by chart review. RESULTS: One hundred eighty-five individuals (83 LAMS, 102 LAMS/DPPS) were identified. No significant differences were found in rates of clinical success (75.9% LAMS vs 69.6% LAMS/DDPS, P = .34) or overall AEs (15.7% LAMS vs 15.7% LAMS/DPPS, P = .825). CONCLUSIONS: In this comparative single-center study, placement of a coaxial DPPS for drainage of PFCs with LAMSs did not affect rates of AEs or clinical success.

Endoscopic Ultrasound-based Shear Wave Elastography for Detection of Advanced Liver Disease.

BACKGROUND AND AIMS: Endoscopic ultrasound shear wave elastography (EUS-SWE) is a novel modality for liver stiffness measurement. The aims of this study are to evaluate the performance and reliability of EUS-SWE for detecting advanced liver disease in a prospective cohort. METHODS: EUS-SWE measurements were prospectively obtained from patients undergoing EUS between August 2020 and March 2023. Liver stiffness measurements were compared between patients with and without advanced liver disease (ALD), defined as stage ≥3, to determine diagnostic accuracy for advanced fibrosis and portal hypertension. Logistic regression was performed to identify variables that impact the reliability of EUS-SWE readings. Select patients underwent paired magnetic resonance elastography (MRE) for liver fibrosis correlation. RESULTS: Patients with ALD demonstrated higher liver stiffness compared to healthy controls (left lobe: 17.6 vs. 12.7 kPa, P<0.001; median right lobe: 24.8 vs. 11.0 kPa, P<0.001). The area under the receiver operator characteristic (AUROC) for the detection of ALD was 0.73 and 0.80 for left and right lobe measurements, respectively. General anesthesia was associated with reliable EUS-SWE liver readings (odds ratio: 2.73, 95% CI: 1.07-7.39, P=0.040). Left lobe measurements correlated significantly with MRE with an increase of 0.11 kPa (95% CI: 0.05-0.17 kPA) for every 1 kPa increase on EUS-SWE. D. CONCLUSIONS: SWE is a promising technology that can readily be incorporated into standard EUS examinations for the assessment of ALD.

AGA Clinical Practice Update on the Endoscopic Approach to Recurrent Acute and Chronic Pancreatitis: Expert Review.

DESCRIPTION: The purpose of this American Gastroenterological Association (AGA) Clinical Practice Update Expert Review is to provide practical, evidence-based guidance to clinicians regarding the role of endoscopy for recurrent acute and chronic pancreatitis. METHODS: This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide guidance on a topic of clinical importance to the AGA membership, underwent internal peer review by the Clinical Practice Updates Committee (CPUC), and external peer review through standard procedures of Gastroenterology. This review is framed around the 8 best practice advice points agreed upon by the authors, based on the results of randomized controlled trials, observational studies, systematic reviews and meta-analyses, as well expert consensus in this field. Best Practice Advice Statements BEST PRACTICE ADVICE 1: After an unrevealing initial evaluation, endoscopic ultrasound is the preferred diagnostic test for unexplained acute and recurrent pancreatitis. Magnetic resonance imaging with contrast and cholangiopancreatography is a reasonable complementary or alternative test to endoscopic ultrasound, based on local expertise and availability. BEST PRACTICE ADVICE 2: The role of endoscopic retrograde cholangiopancreatography (ERCP) for reducing the frequency of acute pancreatitis episodes in patients with pancreas divisum is controversial, but minor papilla endotherapy may be considered, particularly for those with objective signs of outflow obstruction, such as a dilated dorsal pancreatic duct and/or santorinicele. There is no role for ERCP to treat pain alone in patients with pancreas divisum. BEST PRACTICE ADVICE 3: The role of ERCP for reducing the frequency of pancreatitis episodes in patients with unexplained recurrent acute pancreatitis and standard pancreatic ductal anatomy is controversial and should only be considered after a comprehensive discussion of the uncertain benefits and potentially severe procedure-related adverse events. When pursued, ERCP with biliary sphincterotomy alone may be preferable to dual sphincterotomy. BEST PRACTICE ADVICE 4: Surgical intervention should be considered over endoscopic therapy for long-term treatment of patients with painful obstructive chronic pancreatitis. Endoscopic intervention is a reasonable alternative to surgery for suboptimal operative candidates or those who favor a less invasive approach, assuming they are clearly informed that the best practice advice primarily favors surgery. BEST PRACTICE ADVICE 5: When ERCP is pursued, small (≤5mm) main pancreatic duct stones can be treated with pancreatography and conventional stone extraction maneuvers. For larger stones, extracorporeal shockwave lithotripsy and/or pancreatoscopy with intraductal lithotripsy may be required. BEST PRACTICE ADVICE 6: When ERCP is pursued, prolonged stent therapy (6-12 months) is effective for treating symptoms and remodeling main pancreatic duct strictures. The preferred approach is to place and sequentially add multiple plastic stents in parallel (upsizing); emerging evidence suggests that fully covered self-expanding metal stents may have a role for this indication, but additional research is necessary. BEST PRACTICE ADVICE 7: ERCP with stent insertion is the preferred treatment for benign biliary stricture due to chronic pancreatitis. FCSEMS placement is favored over multiple plastic stents whenever feasible, given similar efficacy but significantly reduced need for stent exchange procedures during the treatment course. BEST PRACTICE ADVICE 8: Celiac plexus block should not be routinely performed for the management of pain due to chronic pancreatitis. The decision to proceed with celiac plexus block in selected patients with debilitating pain in whom other therapeutic measures have failed can be considered on a case-by-case basis, but only after discussion of the unclear outcomes of this intervention and its procedural risks.

A Protocolized Management of Walled-Off Necrosis (WON) Reduces Time to WON Resolution and Improves Outcomes.

BACKGROUND AND AIMS: Patients with infected or symptomatic walled-off necrosis (WON) have high morbidity and health care utilization. Despite the recent adoption of nonsurgical treatment approaches, WON management remains nonalgorithmic. We investigated the impact of a protocolized early necrosectomy approach compared with a nonprotocolized, clinician-driven approach on important clinical outcomes. METHODS: Records were reviewed for consecutive patients with WON who underwent a protocolized endoscopic drainage with a lumen-apposing metal stent (cases), and for patients with WON treated with a lumen-apposing metal stent at the same tertiary referral center who were not managed according to the protocol (control subjects). The protocol required repeat cross-sectional imaging within 14 days after lumen-apposing metal stent placement, with regularly scheduled endoscopic necrosectomy if WON diameter reduction was <50%. Control patients were treated according to their clinician's preference without an a priori strategy. Inverse probability of treatment weighting-adjusted analysis was used to evaluate the influence of being in the protocolized group on time to resolution. RESULTS: A total of 24 cases and 47 control subjects were included. There were no significant differences in baseline characteristics. Although numbers of endoscopies and necrosectomies were similar, cases had lower adverse event rates, shorter intensive care unit stay, and required nutritional support for fewer days. On matched multivariate Cox regression, cases had earlier WON resolution (hazard ratio, 5.73; 95% confidence interval, 2.62-12.5). This was confirmed in the inverse probability of treatment weighting-adjusted analysis (hazard ratio, 3.4; 95% confidence interval, 1.92-6.01). CONCLUSIONS: A protocolized strategy resulted in faster WON resolution compared with a discretionary approach without the need for additional therapeutic interventions, and with a better safety profile and decreased health care utilization.

Longitudinal Assessment of SARS-CoV-2-Specific T Cell Cytokine-Producing Responses for 1 Year Reveals Persistence of Multicytokine Proliferative Responses, with Greater Immunity Associated with Disease Severity.

Cell-mediated immunity is critical for long-term protection against most viral infections, including coronaviruses. We studied 23 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected survivors over a 1-year post-symptom onset (PSO) interval by ex vivo cytokine enzyme-linked immunosorbent spot assay (ELISpot) assay. All subjects demonstrated SARS-CoV-2-specific gamma interferon (IFN-γ), interleukin 2 (IL-2), and granzyme B (GzmB) T cell responses at presentation, with greater frequencies in severe disease. Cytokines, mainly produced by CD4+ T cells, targeted all structural proteins (nucleocapsid, membrane, and spike) except envelope, with GzmB and IL-2 greater than IFN-γ. Mathematical modeling predicted that (i) cytokine responses peaked at 6 days for IFN-γ, 36 days for IL-2, and 7 days for GzmB, (ii) severe illness was associated with reduced IFN-γ and GzmB but increased IL-2 production rates, and (iii) males displayed greater production of IFN-γ, whereas females produced more GzmB. Ex vivo responses declined over time, with persistence of IL-2 in 86% and of IFN-γ and GzmB in 70% of subjects at a median of 336 days PSO. The average half-life of SARS-CoV-2-specific cytokine-producing cells was modeled to be 139 days (~4.6 months). Potent T cell proliferative responses persisted throughout observation, were CD4 dominant, and were capable of producing all 3 cytokines. Several immunodominant CD4 and CD8 epitopes identified in this study were shared by seasonal coronaviruses or SARS-CoV-1 in the nucleocapsid and membrane regions. Both SARS-CoV-2-specific CD4+ and CD8+ T cell clones were able to kill target cells, though CD8 tended to be more potent. IMPORTANCE Our findings highlight the relative importance of SARS-CoV-2-specific GzmB-producing T cell responses in SARS-CoV-2 control and shared CD4 and CD8 immunodominant epitopes in seasonal coronaviruses or SARS-CoV-1, and they indicate robust persistence of T cell memory at least 1 year after infection. Our findings should inform future strategies to induce T cell vaccines against SARS-CoV-2 and other coronaviruses.

Identification of patients with malignant biliary strictures using a cholangioscopy-based deep learning artificial intelligence (with video).

BACKGROUND AND AIMS: Accurately diagnosing malignant biliary strictures (MBSs) as benign or malignant remains challenging. It has been suggested that direct visualization and interpretation of cholangioscopy images provide greater accuracy for stricture classification than current sampling techniques (ie, brush cytology and forceps biopsy sampling) using ERCP. We aimed to develop a convolutional neural network (CNN) model capable of accurate stricture classification and real-time evaluation based solely on cholangioscopy image analysis. METHODS: Consecutive patients with cholangioscopy examinations from 2012 to 2021 were reviewed. A CNN was developed and tested using cholangioscopy images with direct expert annotations. The CNN was then applied to a multicenter, reserved test set of cholangioscopy videos. CNN performance was then directly compared with that of ERCP sampling techniques. Occlusion block heatmap analyses were used to evaluate and rank cholangioscopy features associated with MBSs. RESULTS: One hundred fifty-four patients with available cholangioscopy examinations were included in the study. The final image database comprised 2,388,439 still images. The CNN demonstrated good performance when tasked with mimicking expert annotations of high-quality malignant images (area under the receiver-operating characteristic curve, .941). Overall accuracy of CNN-based video analysis (.906) was significantly greater than that of brush cytology (.625, P = .04) or forceps biopsy sampling (.609, P = .03). Occlusion block heatmap analysis demonstrated that the most frequent image feature for an MBS was the presence of frond-like mucosa/papillary projections. CONCLUSIONS: This study demonstrates that a CNN developed using cholangioscopy data alone has greater accuracy for biliary stricture classification than traditional ERCP-based sampling techniques.

Uncovered versus fully covered self-expandable metal stents for the management of distal malignant biliary obstruction.

BACKGROUND AND AIM: Self-expandable metal stents (SEMSs) are widely used for palliation of distal malignant biliary obstruction (dMBO). However, previous studies comparing the outcomes between uncovered SEMSs (UCSEMSs) and fully covered SEMSs (FCSEMSs) report conflicting results. This large cohort study aimed to compare the clinical outcomes between UCSEMSs and FCSEMSs for dMBO. METHODS: A retrospective cohort study was performed in patients with dMBO who underwent either UCSEMS or FCSEMS placement between May 2017 and May 2021. Primary outcomes were rates of clinical success, adverse events (AEs), and unplanned endoscopic reintervention. Secondary outcomes were types of AEs, intervention-free stent patency, and management and outcomes of stent occlusion. RESULTS: The cohort included 454 patients (364 in the UCSEMS group and 90 in the FCSEMS group). Median follow-up duration was 9.6 months and was similar between the 2 groups. Use of UCSEMSs and FCSEMSs had comparable clinical success (P = .250). However, use of UCSEMSs had significantly higher rates of AEs (33.5% vs 21.1%; P = .023) and unplanned endoscopic reintervention (27.0% vs 11.1%; P = .002). UCSEMSs had a higher rate of stent occlusion (26.9% vs 8.9%; P < .001) and shorter median time to stent occlusion (4.4 months vs 10.7 months; P = .002). Stent reintervention-free survival was higher in the FCSEMS group. FCSEMSs had a significantly higher rate of stent migration (7.8% vs 1.1%; P < .001), but patients in the FCSEMS group had similar rates of cholecystitis (.3% vs 1.1%; P = .872) and post-ERCP pancreatitis (6.3% vs 6.6%; P = .90). When UCSEMSs did occlude, placement of a coaxial plastic stent had a higher rate of stent reocclusion compared with coaxial SEMS placement (46.7% vs 19.7%; P = .007). CONCLUSION: FCSEMSs should be considered for the palliation of dMBO because of lower rates of AEs, longer patency rates, and lower rates of unplanned endoscopic intervention.

Novel classification system for walled-off necrosis: a step toward standardized nomenclature and risk-stratification framework.

BACKGROUND AND AIMS: The optimal therapeutic approach for walled-off necrosis (WON) is not fully understood, given the lack of a validated classification system. We propose a novel and robust classification system based on radiologic and clinical factors to standardize the nomenclature, provide a framework to guide comparative effectiveness trials, and inform the optimal WON interventional approach. METHODS: This was a retrospective analysis of patients who underwent endoscopic management of WON by lumen-apposing metal stent placement at a tertiary referral center. Patients were classified according to the proposed QNI classification system: quadrant ("Q"), represented an abdominal quadrant distribution; necrosis ("N"), denoted by the percentage of necrosis of WON; and infection ("I"), denoted as positive blood culture and/or systemic inflammatory response syndrome reaction with a positive WON culture. Two blinded reviewers classified all patients according to the QNI system. Patients were then divided into 2 groups: those with a lower QNI stratification (≤2 quadrants and ≤30% necrosis; group 1) and those with a higher stratification (≥3 quadrants, 2 quadrants with ≥30% necrosis, or 1 quadrant with >60% necrosis and infection; group 2). The primary outcome was mean time to WON resolution. Secondary procedural and clinical outcomes between the groups were compared. RESULTS: Seventy-one patients (75% men) were included and stratified by the QNI classification; group 1 comprised 17 patients and group 2, 54 patients. Patients in group 2 had a higher number of necrosectomies, longer hospital stays, and more readmissions. The mean time to resolution was longer in group 2 than in group 1 (79.6 ± 7.76 days vs 48.4 ± 9.22 days, P = .02). The mortality rate was higher in group 2 (15% vs 0%, P = .18). CONCLUSIONS: Despite the heterogeneous nature of WON in severe acute pancreatitis, a proposed QNI system may provide a standardized framework for WON classification to inform clinical trials, risk-stratify the disease course, and potentially inform an optimal management approach.

A novel blood-sensing capsule for rapid detection of upper GI bleeding: a prospective clinical trial.

BACKGROUND AND AIMS: Upper GI bleeding (UGIB) is a common medical emergency associated with high resource utilization, morbidity, and mortality. Timely EGD can be challenging from personnel, resource, and access perspectives. PillSense (EnteraSense Ltd, Galway, Ireland) is a novel swallowed bleeding sensor for the detection of UGIB, anticipated to aid in patient triage and guide clinical decision-making for individuals with suspected UGIB. METHODS: This prospective, open-label, single-arm comparative clinical trial of a novel bleeding sensor for patients with suspected UGIB was performed at a tertiary care center. The PillSense system consists of an optical sensor and an external receiver that processes and displays data from the capsule as "Blood Detected" or "No Blood Detected." Patients underwent EGD within 4 hours of capsule administration; participants were followed up for 21 days to confirm capsule passage. RESULTS: A total of 126 patients were accrued to the study (59.5% male; mean age, 62.4 ± 14.3 years). Sensitivity and specificity for detecting the presence of blood were 92.9% (P = .02) and 90.6% (P < .001), respectively. The capsule's positive and negative predictive values were 74.3% and 97.8%, and positive and negative likelihood ratios were 9.9 and .08. No adverse events or deaths occurred related to the PillSense system, and all capsules were excreted from patients on follow-up. CONCLUSIONS: The PillSense system is safe and effective for detecting the presence of blood in patients evaluated for UGIB before upper GI endoscopy. It is a rapidly deployed tool, with easy-to-interpret results that will affect the diagnosis and triage of patients with suspected UGIB. (Clinical trial registration number: NCT05385224.).

Lumen-apposing metal stents for the treatment of benign gastrointestinal tract strictures: a single-center experience and proposed treatment algorithm.

BACKGROUND: Lumen-apposing metal stents (LAMS) are an alternative therapeutic option for benign gastrointestinal (GI) tract strictures. Our study aimed to evaluate the safety and efficacy of LAMS for the management of benign GI strictures. METHODS: Consecutive patients who underwent a LAMS placement for benign luminal GI strictures at a tertiary care center between January 2014 and July 2021 were reviewed. Primary outcomes included technical success, early clinical success, and adverse events (AEs). Other outcomes included rates of stent migration and re-intervention after LAMS removal. RESULTS: One hundred and nine patients who underwent 128 LAMS placements (67.9% female, mean age of 54.3 ± 14.2 years) were included, and 70.6% of the patients had failed prior endoscopic treatments. The majority of strictures (83.5%) were anastomotic, and the most common stricture site was the gastrojejunal anastomosis (65.9%). Technical success was achieved in 100% of procedures, while early clinical success was achieved in 98.4%. The overall stent-related AE rate was 25%. The migration rate was 27.3% (35/128). Of these, five stents were successfully repositioned endoscopically. The median stent dwell time was 119 days [interquartile range (IQR) 68-189 days], and the median follow-up duration was 668.5 days [IQR: 285.5-1441.5 days]. The re-intervention rate after LAMS removal was 58.3%. CONCLUSIONS: LAMS is an effective therapeutic option for benign GI strictures, offering high technical and early clinical success. However, the re-intervention rate after LAMS removal was high. In select cases, using LAMS placement as destination therapy with close surveillance is a reasonable option.

Endoscopic ultrasound-guided versus percutaneous drainage for the management of post-operative fluid collections after distal pancreatectomy.

BACKGROUND: Post-operative pancreatic fluid collections (POPFCs) can be drained using percutaneous or endoscopic approaches. The primary aim of this study was to compare rates of clinical success between endoscopic ultrasound-guided drainage (EUSD) with percutaneous drainage (PTD) in the management of symptomatic POPFCs after distal pancreatectomy. Secondary outcomes included technical success, total number of interventions, time to resolution, rates of adverse events (AEs), and POPFC recurrence. METHODS: Adults who underwent distal pancreatectomy from January 2012 to August 2021 and developed symptomatic POPFC in the resection bed were retrospectively identified from a single academic center database. Demographic data, procedural data, and clinical outcomes were abstracted. Clinical success was defined as symptomatic improvement and radiographic resolution without requiring an alternate drainage modality. Quantitative variables were compared using a two-tailed t-test and categorical data were compared using Chi-squared or Fisher's exact tests. RESULTS: Of 1046 patients that underwent distal pancreatectomy, 217 met study inclusion criteria (median age 60 years, 51.2% female), of whom 106 underwent EUSD and 111 PTD. There were no significant differences in baseline pathology and POPFC size. PTD was generally performed earlier after surgery (10 vs. 27 days; p < 0.001) and more commonly in the inpatient setting (82.9% vs. 49.1%; p < 0.001). EUSD was associated with a significantly higher rate of clinical success (92.5% vs. 76.6%; p = 0.001), fewer median number of interventions (2 vs. 4; p < 0.001), and lower rate of POPFC recurrence (7.6% vs. 20.7%; p = 0.007). AEs were similar between EUSD (10.4%) and PTD (6.3%, p = 0.28), with approximately one-third of EUSD AEs due to stent migration. CONCLUSION: In patients with POPFCs after distal pancreatectomy, delayed drainage with EUSD was associated with higher rates of clinical success, fewer interventions, and lower rates of recurrence than earlier drainage with PTD.

Utility of Urgent Endoscopic Retrograde Cholangiopancreatography in Patients with Predicted Mild Acute Pancreatitis and Cholestasis.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) within 72 h is suggested for patients presenting with acute biliary pancreatitis (ABP) and biliary obstruction without cholangitis. This study aimed to identify if urgent ERCP (within 24 h) improved outcomes compared to early ERCP (24-72 h) in patients admitted with predicted mild ABP. METHODS: Patients admitted for predicted mild ABP defined as a bedside index of severity in acute pancreatitis score < 3 and underwent ERCP for biliary obstruction within 72 h of presentation during the study period were included. Patients with prior biliary sphincterotomy or surgically altered anatomy preventing conventional ERCP were excluded. The primary outcome was the development of moderately severe or severe pancreatitis based on the revised Atlanta classification. Secondary outcomes were the length of hospital stay, the need for ICU admission, and ERCP-related adverse events (AEs). RESULTS: Of the identified 166 patients, baseline characteristics were similar between both the groups except for the WBC count (9.4 vs. 8.3/µL; p < 0.044) and serum bilirubin level (3.0 vs. 1.6 mg/dL; p < 0.0039). Biliary cannulation rate and technical success were both high in the overall cohort (98.8%). Urgent ERCP was not associated with increased development of moderately severe pancreatitis (10.4% vs. 15.7%; p = 0.3115). The urgent ERCP group had a significantly shorter length of hospital stay [median 3 (IQR 2-3) vs. 3 days (IQR 3-4), p < 0.01]. CONCLUSION: Urgent ERCP did not impact the rate of developing more severe pancreatitis in patients with predicted mild ABP but was associated with a shorter length of hospital stay and a lower rate of hospital readmission.

Gastric per-oral endoscopic myotomy (G-POEM) for refractory gastroparesis: results from an international prospective trial.

OBJECTIVE: Although gastric per-oral endoscopic myotomy (G-POEM) is considered a promising technique for the management of refractory gastroparesis, high-quality evidence is limited. We prospectively investigated the efficacy and safety of G-POEM in unselected patients with refractory gastroparesis. DESIGN: In five tertiary centres, patients with symptomatic gastroparesis refractory to standard medical therapy and confirmed by impaired gastric emptying were included. The primary endpoint was clinical success, defined as at least one score decrease in Gastroparesis Cardinal Symptom Index (GCSI) with ≥25% decrease in two subscales, at 12 months. GCSI Score and subscales, adverse events (AEs) and 36-Item Short Form questionnaire of quality of life were evaluated at baseline and 1, 3, 6 and 12 months after G-POEM. Gastric emptying study was performed before and 3 months after the procedure. RESULTS: Of 80 enrolled patients, 75 patients (94%) completed 12-month follow-up. Clinical success at 12 months was 56% (95% CI, 44.8 to 66.7). GCSI Score (including subscales) improved moderately after G-POEM (p<0.05). In a regression model, a baseline GCSI Score >2.6 (OR=3.23, p=0.04) and baseline gastric retention >20% at 4 hours (OR=3.65, p=0.03) were independent predictors of clinical success at 12 months, as was early response to G-POEM at 1 month after therapy (OR 8.75, p<0.001). Mild procedure-related AEs occurred in 5 (6%) patients. CONCLUSION: G-POEM is a safe procedure, but showed only modest overall effectiveness in the treatment of refractory gastroparesis. Further studies are required to identify the best candidates for G-POEM; unselective use of this procedure should be discouraged. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry NCT02732821.

Lists with and without Syntax: A New Approach to Measuring the Neural Processing of Syntax.

In the neurobiology of syntax, a methodological challenge is to vary syntax while holding semantics constant. Changes in syntactic structure usually correlate with changes in meaning. We approached this challenge from a new angle. We deployed word lists-typically, the unstructured control in studies of syntax-as both test and control stimuli. Three-noun lists ("lamps, dolls, guitars") were embedded in sentences ("The eccentric man hoarded lamps, dolls, guitars…") and in longer lists ("forks, pen, toilet, rodeo, lamps, dolls, guitars…"). This allowed us to minimize contributions from lexical semantics and local phrasal combinatorics: the same words occurred in both conditions, and in neither case did the list items locally compose into phrases (e.g., "lamps" and "dolls" do not form a phrase). Crucially, the list partakes in a syntactic tree in one case but not the other. Lists-in-sentences increased source-localized MEG activity at ∼250-300 ms from each of the list item onsets in the left inferior frontal cortex, at ∼300-350 ms in the left anterior temporal lobe and, most reliably, at ∼330-400 ms in left posterior temporal cortex. In contrast, the main effects of semantic association strength, which we also varied, localized in the left temporoparietal cortex, with high associations increasing activity at ∼400 ms. This dissociation offers a novel characterization of the structure versus word meaning contrast in the brain: the frontotemporal network that is familiar from studies of sentence processing can be driven by the sheer presence of global sentence structure, while associative semantics has a more posterior neural signature.SIGNIFICANCE STATEMENT Human languages all have a syntax, which both enables the infinitude of linguistic creativity and determines what is grammatical in a language. The neurobiology of syntactic processing has, however, been challenging to characterize despite decades of study. One reason is pure manipulations of syntax are difficult to design. The approach here offers a novel control of two variables that are notoriously hard to keep constant when syntax is manipulated: word meaning and phrasal combinatorics. The same noun lists occurred inside longer lists and sentences, while semantic associations also varied. Our MEG results show that classic frontotemporal language regions can be driven by sentence structure even when local semantic contributions are absent. In contrast, the left temporoparietal junction tracks associative relationships.

Therapeutic endoscopic ultrasound: European Society of Gastrointestinal Endoscopy (ESGE) Technical Review.

1: ESGE recommends a prolonged course of a prophylactic broad-spectrum antibiotic in patients with ascites who are undergoing therapeutic endoscopic ultrasound (EUS) procedures.Strong recommendation, low quality evidence. 2: ESGE recommends placement of partially or fully covered self-expandable metal stents during EUS-guided hepaticogastrostomy for biliary drainage in malignant disease.Strong recommendation, moderate quality evidence. 3: ESGE recommends EUS-guided pancreatic duct (PD) drainage should only be performed in high volume expert centers, owing to the complexity of this technique and the high risk of adverse events.Strong recommendation, low quality evidence. 4: ESGE recommends a stepwise approach to EUS-guided PD drainage in patients with favorable anatomy, starting with rendezvous-assisted endoscopic retrograde pancreatography (RV-ERP), followed by antegrade or transmural drainage only when RV-ERP fails or is not feasible.Strong recommendation, low quality evidence. 5: ESGE suggests performing transduodenal EUS-guided gallbladder drainage with a lumen-apposing metal stent (LAMS), rather than using the transgastric route, as this may reduce the risk of stent dysfunction.Weak recommendation, low quality evidence. 6: ESGE recommends using saline instillation for small-bowel distension during EUS-guided gastroenterostomy.Strong recommendation, low quality evidence. 7: ESGE recommends the use of saline instillation with a 19G needle and an electrocautery-enhanced LAMS for EUS-directed transgastric endoscopic retrograde cholangiopancreatography (EDGE) procedures.Strong recommendation, low quality evidence. 8: ESGE recommends the use of either 15- or 20-mm LAMSs for EDGE, with a preference for 20-mm LAMSs when considering a same-session ERCP.Strong recommendation, low quality evidence.