Gastroenterology

BackgroundBarretts esophagus (BE), characterized by specialized intestinal metaplasia (SIM), is the precursor to esophageal adenocarcinoma (EAC). Despite published BE screening guidelines for at-risk individuals, uptake of endoscopic screening remains low. We present 18 months of real-world data on non-endoscopic BE screening using EsoGuard(R) (EG), the first commercially available U.S. molecular biomarker test for this purpose, performed on esophageal cell samples collected with the swallowable EsoCheck(R) (EC) balloon-capsule device. MethodsWe retrospectively analyzed EC performance and EG results in patients tested commercially from January 2023 to June 2024. A subset enrolled in a registry underwent follow-up endoscopy. Multivariable logistic regression was used to evaluate risk factors associated with (1) positive EG results, and (2) confirmed BE (SIM [&ge;]1 cm). ResultsAmong 11,991 tested patients, 11,355 (94.7%) had successful EC cell collection, averaging under 2 minutes with no serious adverse events. EG was positive in 16.6% of patients, with positivity increasing by age; age > 50 years was the strongest individual risk factor for predicting a positive EG result. Among 177 EG-positive registry patients who underwent endoscopy, 59 (33.3%) had SIM, of which 33 met American College of Gastroenterology criteria for BE and 26 had ultra-short SIM (<1 cm). Dysplasia was found in 3 patients: 1 HGD, 1 LGD, and 1 indefinite for dysplasia (IND). ConclusionsWe report here the largest real-world experience of EG and EC to date, demonstrating excellent safety, tolerability, and scalability. EG detects both guideline-recognized and ultra-short SIM, supporting its utility as a non-invasive BE screening tool.

Background and study aimsEndoscopic resection (ER) is curative for early-stage oesophageal adenocarcinoma (OAC) without high-risk features. Piecemeal endoscopic mucosal resection (pEMR) prevents assessment of lateral margins, complicating risk estimation for neoplastic recurrence. We investigated risk factors for residual and recurrent OAC post-pEMR. MethodsWe performed a longitudinal study of two independent patient cohorts: the test cohort, who underwent piecemeal or en-bloc ER, (n=138) and the validation cohort, treated with pEMR only (n=89). Inclusion criteria were: OAC stage T1a or low-risk T1b, no lympho-vascular invasion, and R0 resection. The primary outcome was residual OAC at first post-ER endoscopy, and secondary outcomes were residual high-grade dysplasia (HGD), recurrence of neoplasia at any post-ER endoscopy, and remission of neoplasia and metaplasia at most recent endoscopy. ResultsIn the test cohort, the incidence of HGD recurrence was higher in patients treated with pEMR versus en-bloc ER (p=0.021). The percentage of pEMR specimens with OAC was an independent risk factor for residual OAC at the first post-pEMR endoscopy (OR for a 10% increase=1.21, CI=1-1.46, p=0.044). A 50% cut-off of involved pEMR specimens was optimal to predict residual OAC (specificity=0.69, sensitivity=0.63). Rates of residual (p=0.02) and recurrent (p=0.0024) OAC were higher when >50% of pEMR specimens were involved by OAC. In the validation cohort, recurrent OAC was also more frequent when cancer burden was >50% (p=0.013). ConclusionsHigh OAC burden on pEMR specimens correlates with the risk of residual OAC. Post-pEMR site check before endoscopic ablation is recommended if more than 50% of pEMR specimens show OAC.

Background and AimsBarretts Esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). We aimed to assess performance, safety, and tolerability of the EsoGuard (EG) assay on samples collected non-endoscopically with the EsoCheck (EC) device (EG/EC) for BE detection in the intended-use population, meeting American College of Gastroenterology (ACG) guideline criteria (chronic gastroesophageal reflux disease (GERD) and 3+ additional risk factors). MethodsWe performed a prospective, multicenter study (NCT04293458) to assess EG performance (primary endpoint) on cells collected with EC, for detection of BE and EAC using esophagogastroduodenoscopy (EGD) and biopsies as the comparator. Twenty-four sites across the U.S. and Spain participated. EC safety and usability were assessed as secondary endpoints. Results180 male subjects aged >50 years with chronic GERD met eligibility criteria, of which 163 (90.6%) had EGD and successful EC administration. Mean age was 60.5yrs, 34.4% were obese, 56.7% had tobacco history, and 3.9% had a 1st degree relative with BE or EAC. Of 122 samples analyzed, 93 contributed to the primary endpoint analysis. About 9% of subjects in the Primary Analysis Population had BE on EGD, none with dysplasia. Sensitivity of EG for BE was 87.5% (95% CI 47.4-99.7), specificity was 81.2% (95% CI 71.2-88.8), positive predictive value was 30.4% (95% CI 13.2-52.9), and negative predictive value was 98.6% (95% CI 92.3-99.96). Mild esophageal abrasions were observed in 1.5%; no serious adverse events were reported. ConclusionsEG/EC appears effective for BE screening. This approach provides a safe, accurate, and well-tolerated non-endoscopic alternative in high-risk patients.

BackgroundEosinophilic Esophagitis (EoE) is a chronic inflammatory condition diagnosed by [&ge;]15 eosinophils (Eos) per high-power field (HPF). There is no gold standard for clinical remission and Eo-associated metrics are poorly correlated with symptoms. Deep learning can be used to explore the relationships of tissue features with clinical response. ObjectivesTo determine if deep learning can elucidate tissue patterns in EoE that predict treatments or symptoms at remission. MethodsWe created two deep learning models using esophageal biopsies from histologically normal and EoE patients: one to identify Eos in esophageal biopsies and a second to broadly classify esophageal tissue as EoE vs. normal. We used these models to analyze biopsies at diagnosis and first remission timepoint, as defined by <15 Eos/HPF, in a subset of 19 treatment-naive patients. Differences in deep learning metrics between patient groups were assessed using Wilcoxon Rank-Sum tests. ResultsAll initial patients were symptomatic at diagnosis and a majority were still suffering from dysphagia at remission. The Eo identification model had a low mean (SD) error of -0.3 (11.5) Eos/HPF. Higher peak and average Eo counts at diagnosis were associated with higher likelihood of being on a food-elimination diet at remission than steroids or proton-pump inhibitor (p<0.05). The EoE classification model had an F1-score of 0.97 for distinguishing normal tissue from EoE. There was a significant decrease from diagnosis in the percentage of EoE-classified tissue among asymptomatic remission patients (p<0.05). ConclusionsDeep learning may have utility in diagnosing EoE and predicting future treatment response at diagnosis and resolution of symptoms at follow-up. Clinical Implications or Key Messages (for mechanistic article)We developed two deep learning approaches for tissue analysis in eosinophilic esophagitis, which may improve histologic assessment of patients at diagnosis and predict treatment response and symptoms at remission. Capsule summaryTwo deep learning approaches for eosinophilic esophagitis (EoE): (1) Quantification of eosinophils throughout an entire biopsy, which predicted treatment at remission (2) Classifying esophageal tissue as EoE or normal, which predicted symptoms at remission.

BackgroundFirefighters have frequent exposure to compounds shown to increase risk of esophageal neoplasia. EsoGuard(R) (EG) is a DNA biomarker assay that can be utilized with efficiency and high tolerability as a triage to endoscopy for diagnosis of patients with Barretts Esophagus (BE), a known precursor to esophageal adenocarcinoma (EAC). This diagnostic tool may facilitate disease testing among busy at-risk firefighters. MethodsRetrospective analysis of prospectively collected clinical utility (CU) data for use of EG as a triage to more invasive endoscopic evaluation. EG was performed on esophageal cell samples collected with the nonendoscopic EsoCheck(R) (EC) device during two large cancer and pre-cancer screening events for firefighters in San Antonio, TX, in January 2023. CU was evaluated by provider impact assessment. Results388 firefighters were identified for EG testing, of which >99% (385/388) successfully completed EC cell collection. Over 96% (372/385) of tests had binary results; the remaining <4% failed analysis due to insufficient DNA. The EG positivity rate was 7.3% (28/385), all of whom were referred for specialist and upper endoscopy evaluation. Among those who tested negative, none were referred for further diagnostic workup. This represented a 100% concordance between EG results and physician management decisions. ConclusionsThis study capturing real-world data on use of EG in a population of firefighters demonstrates its ability to test many individuals rapidly and efficiently in a well-tolerated fashion, and reliable use of the test to triage individuals prior to pursuing more invasive and time-consuming diagnostic approaches.

BackgroundAbnormal gastric myoelectrical function may contribute to gastroesophageal reflux disease (GERD). We assessed if myoelectrical abnormalities measured using body surface gastric mapping were correlated with reflux measured by 24 hr pH testing, and symptom severity. MethodsGastric Alimetry(R) was performed simultaneously on patients undergoing 24 hr pH testing for investigation of reflux symptoms, with a standardised 4.5 hr test and validated symptom logging. Data were segmented into 15-minute epochs. Correlations between myoelectric activity, reflux events, and symptoms were assessed, including temporal correlations adjusted for repeated measures. ResultsForty subjects were recruited (mean age 46.5 years, 60% female): 20 undergoing pH testing (12 with GERD and 8 symptomatic patients without), and 20 controls. GERD patients displayed less stable Gastric Alimetry(R) Rhythm-Index (GA-RI) compared with controls (p=0.011), but not with non-GERD patients (p=0.605). Decreasing GA-RI was associated with esophageal acid exposure (DeMeester score; r=-0.46, p=0.042). Periods of decreased GA-RI were not temporally correlated with reflux (r=0.08, p=0.182), or heartburn severity (r=0.04, p=0.309), but were correlated with nausea (r=-0.22, p<0.001) and excessive fullness (r=-0.28, p<0.001). ConclusionGastric rhythm instability is associated with increased symptom severity and overall acid exposure in GERD patients, although no temporal link to heartburn was found. Reduced rhythm stability was temporally associated with increased nausea and fullness. GA-RI offers an emerging biomarker of gastric dysfunction in patients with GERD symptomatology. Study highlightsO_ST_ABSWhat is knownC_ST_ABS[bullet] Heartburn is common and often medically refractory [bullet]Gastric conduction and motility abnormalities may contribute to symptoms but the temporal relationship is unknown What is new here[bullet] Gastric rhythm abnormalities measured by Gastric Alimetry(R) are correlated with increasing reflux burden and symptom severity [bullet]There is no temporal association between gastric rhythm and reflux events [bullet]Gastric rhythm abnormalities may predispose patients to worse reflux, but there is no direct temporal correlation

BackgroundBarretts Esophagus (BE) is the only known precursor for esophageal adenocarcinoma (EAC), a highly lethal malignancy which has had increasing incidence in Western populations over the last 40 years. Recommendations are for endoscopic screening of patients with multiple risk factors for BE, however most eligible patients are not undergoing such evaluation, or failing to be referred, leading to most patients with EAC being diagnosed without an existing BE diagnosis. EsoGuard(R) (EG) is a commercially available biomarker test for detection of BE, and when used to analyze cells collected non-endoscopically with EsoCheck(R) (EC), may serve as an easily accessible and well-tolerated diagnostic tool that has been recognized by the ACG and AGA as a reasonable alternative to screening endoscopy. The aim of this study was to evaluate the clinical utility of EG as a triage test for upper endoscopy in the diagnose BE in real world use. MethodsWe present the first data snapshot from a multi-center, observational trial evaluating the CLinical Utility of EsoGuard (CLUE) among physicians who have adopted the technology into their clinical practice. At the time of data snapshot, four centers had contributed to enrollment of 275 subjects between February 23, 2023, to July 28, 2023. Participating centers followed their own standard practices for determining whom to test with EG on cells collected with EC and subsequent management of the patient following results. Demographics, risk factors, test results, and subsequent management decisions were collected and analyzed. The clinical utility of the technology was evaluated based on the impact of the EG test results on the ordering physicians decision to refer or not refer a patient for further endoscopic evaluation. ResultsAmong 275 subjects contributing data for analysis, the average age was 61.9 years, and there was a similar distribution among males and females. Eighty-nine-point seven percent (89.7%) reported a history of chronic GERD, and 73.8% had GERD plus an additional 3 BE risk factors (i.e., ACG screening cohort). 232 subjects had EG results documented at the time of data analysis, among which 229 also had a physician decision on endoscopy referral. Total EG positivity rate was 29.3% (68/232) and 65.5% (152/232) were negative; the positive agreement between positive EG results and referral for endoscopy was 100%. The negative agreement between a negative EG result and non-referral for endoscopy was 99.3%. The overall concordance between EG result and endoscopy referral was 98.8%. This did not substantially differ between the ACG screening cohort compared to others. ConclusionsData from the first snapshot of the CLUE study demonstrates physicians ordering EC/EG in the commercial setting are reliably utilizing EG results as a triage tool to guide referrals for endoscopic evaluation of BE. Physicians always refer EG(+) individual for additional endoscopic evaluation, whereas EG(-) subjects are consistently being spared an invasive test.

BackgroundBarretts Esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC), and guidelines exist for screening, surveillance, and treatment. However, historically most high-risk individuals have not been reliably screened, likely due to a combination of factors associated with patient/physician awareness and use of upper endoscopy (UE) as the traditional screening test. EsoGuard(R) (EG) is a DNA biomarker assay, and EsoCheck(R) (EC) is a non-invasive, swallowable capsule device designed to collect cells from a targeted region of the esophagus. EG and EC in combination offers a well-tolerated, accessible, in-office triage test to improve detection of BE in patients with multiple risk factors. The Lucid Registry captures real-world data from the commercial use of EC with EG, and we present an interim review of clinical utility data from the first 517 enrolled subjects. MethodsMulticenter, prospective, registry designed to capture data from patients undergoing EC cell collection and EG testing in the commercial setting. Data collection consists of demographics, risk factors, test results, provider management, and early clinical outcomes (through a maximum of four months post-EG). This data snapshot includes subjects enrolled from the start of the registry (April 14, 2023), through August 16, 2023. The primary assessment of clinical utility was agreement between EG assay results and physicians decision on whether to refer the patient for subsequent UE. The relationship between BE/EAC risk factors and EG positivity rates was assessed. ResultsAmong 517 subjects enrolled, average age was 47.9{+/-}14.3 years, 47.2% had history of gastroesophageal reflux disease (GERD), and 63.8% had a minimum of 3 established BE risk factors (i.e., met American Gastroenterological Association (AGA) criteria for screening). 58.8% of subjects were firefighters; when firefighting i.e., occupational exposure to smoke and carcinogens is treated as an additional BE/EAC risk factor (+) those of the AGA, 81.2% of the study population had [&ge;]3 risks, making up the "AGA(+)" cohort. EG positivity was 14.1%. 437 subjects contributed data for the clinical utility endpoint: agreement between positive EG results and subsequent referral for UE was 100%; agreement between negative EG results and non-referral for UE was 99.4%; concordance between EG results and UE referral decisions was 97.9%. These findings were comparable between the AGA and AGA(+) cohorts. ConclusionsExperience from the Lucid Registry demonstrates that physicians who have adopted EC/EG in the commercial setting are reliably utilizing EG as a triage test to inform decision making on which patients to refer for further endoscopic evaluation of BE.

Metastatic pancreatic ductal adenocarcinoma (PDAC) remains deadly, with minimal improvement in prognosis over the past 20 years despite expansion of our chemotherapeutic arsenal. The complex tumor microenvironment (TME) of PDAC in the advanced stage, which often accompany clinical diagnosis, likely contributes to the limited efficacy of current standard of care chemotherapy. Informed by mechanistic preclinical studies, we evaluated the impact of inhibition of Hedgehog (Hh) signaling to prime PDAC TME and leverage anti-tumor efficacy of Gemcitabine plus nab-Paclitaxel (GnP) together with anti-CTLA-4 immune check point inhibitor (ICI, zalifrelimab). Hh inhibition using NLM-001 (an oral small molecule inhibitor of Smo) aimed to polarize the PDAC TME, including cancer associated fibroblasts (CAFs) and intratumoral immune profile, and to foster an immunosuppressive milieu that engages ICI. In this Phase 1b/2, open label, single arm study, patients with metastatic PDAC received standard GnP every 28-day cycles. In addition, NLM-001 was given at 800 mg daily on days -4 to -1 and days 10 to 13 of the GnP cycles 1 to 3, 6 to 8, 11 to 13 onwards (3 cycles on, followed by 2 rest cycles). Anti CTLA-4 inhibitor, zalifrelimab, was administered at 1mg/kg on day 15 of cycle 1 and every 6 weeks thereafter. The primary end point was to assess efficacy by objective response rate (ORR) as per RECIST v1.1. Treatment was overall well tolerated in the 28 patients enrolled. Most frequent grade 3-4 adverse events (AEs) were neutropenia (46.4%), asthenia (21.4%), and neurotoxicity (14.3%). No patient discontinued treatment due to toxicity. ORR was 50% [95% CI, 29.1-70.9] and disease control rate was 95.5% [95% CI, 86.8 - 100.0]. Median progression-free survival (PFS) was 7.3 months 95.5% [95% CI, 5.564 - 9.041] and median overall survival (OS) was 11.5 months [95% CI, 10.23 -12.73]; 1-year PFS was 18.2% [95% CI, 2.1 - 34.3] and 1-year OS was 50% [95% CI, 29.0 - 710]. Patients who achieved ctDNA clearance at cycle 4 had a significant better PFS (10.7 vs 6.0 months; p<0.0001). Paired biopsies immunolabeling and spatial transcriptomic analyses showed polarization of the TME, with increased CD4+ and CD8+ T cells infiltration, down trending Tregs, and decreased SMA/FAP ratio. Hedgehog inhibitor NLM-001 in combination with gemcitabine/nab-paclitaxel and zalifrelimab was safe and well tolerated and showed encouraging objective responses in the first line treatment of advanced PDAC. Clinical Trial RegistrationEudraCT: 2020-004932-52; NCT04827953.

BackgroundGuidelines support Barretts esophagus (BE) screening, but most eligible patients do not undergo endoscopic evaluation; non-endoscopic strategies are now supported as a reasonable alternative by U.S gastroenterology societies. EsoGuard (EG) is a DNA assay used with EsoCheck, a non-endoscopic cell collection device for detection of BE, which can be utilized as a triage to esophagogastroduodenoscopy (EGD) in patients meeting screening criteria. In doing so, EG may serve to enrich the population undergoing EGD, resulting in more BE diagnoses while potentially reducing utilization of already-limited endoscopy resources. AimTo test the hypothesis that BE detection in EGDs performed on EG positive patients will be significantly higher than the positive predictive value (PPV) of screening EGD alone. MethodsReal-world data was retrospectively collected from EG positive patients for whom EGD diagnoses were available. Baseline patient characteristics, risk factors, and EGD results were obtained from the treating physicians. PPV of screening EGDs was the comparator and estimated by literature-established disease prevalence of BE, which in the U.S gastroesophageal reflux disease population is [~]10.6%. The hypothesis was tested using t-tests for single proportions at a one-sided 5% significance level. ResultsData from 209 patients found 60 (28.7%) subjects with salmon-colored mucosa on EGD and specialized intestinal metaplasia on histopathology. However, 10 (4.8%) had < 1cm of disease on visual inspection, therefore, did not meet the American College of Gastroenterology definition of BE so was excluded from the analysis. Of the remaining 199 patients, 50 (25.1%) had BE on EGD. In the cohort of patients meeting ACG screening criteria, 28.9% (33/114) had BE. Overall, a 2.4-fold increase in BE detection was observed compared to the PPV of screening EGD, and in the ACG cohort this increase was 2.7-fold. Among ACG patients [&ge;]65 years old, the increase was nearly 2.5-fold (25.9% detection rate). ConclusionsOur data suggests EG and EC used as a triage test enriches the population undergoing EGD for BE, and compared to screening EGD alone, can help direct more efficient use of endoscopy resources to unburden the system without reducing the number of eligible patients screened and diagnosed.

BackgroundSodium-Glucose Cotransporter Protein 2 Inhibitors (SGLT2Is) are known for their cardiovascular and renoprotective benefits and are efficacious in managing Metabolic-Associated Steatotic Liver Disease (MASLD). However, limited data exist on their use in advanced liver disease, particularly liver cirrhosis. AimsTo synthesize existing evidence on the efficacy and safety of SGLT2Is in patients with liver cirrhosis and to provide clinical guidance. MethodsA systematic review and meta-analysis were conducted following the PRISMA 2020 Statement. Searches in major health databases identified studies where SGLT2Is were used in patients with cirrhosis. The analysis focused on prospective trials in decompensated cirrhosis and retrospective studies in compensated cirrhosis. Primary outcomes included the need for large-volume paracentesis (LVP) and mortality. Secondary outcomes assessed weight loss, loop diuretic dose reduction, residual ascites, acute kidney injury (AKI), hyponatremia, hepatic encephalopathy (HE), and urinary tract infections (UTIs). ResultsTen studies (8 peer-reviewed) from 2020-2024 were included: 2 randomized controlled trials, 4 single-arm prospective trials, and 4 retrospective studies. SGLT2I use was associated with reduced LVP (RR 0.45, CI 0.31-0.66, p<0.001) and mortality (aHR 0.46, CI 0.38-0.55, p<0.001). Benefits included a 39 mg reduction in loop diuretic dose, 7 kg weight loss, and no significant increase in residual ascites, AKI, hyponatremia, HE, or UTIs. ConclusionsSGLT2Is show promise in managing diuretic-resistant ascites and reducing mortality in liver cirrhosis without causing significant adverse events. Larger, randomized controlled trials are needed to validate these findings.

IntroductionHereditary diffuse gastric cancer (HDGC) associated with CDH1 germline pathogenic variants (GPV), carries a high lifetime risk of signet ring cell carcinoma (SRCC). Currently, there is uncertainty regarding to whom and when to recommend prophylactic total gastrectomy (PTG). We hypothesise a small number of early SRCC lesions correlates with low risk of progression to clinical gastric cancer. This study aimed to identify predictors of early SRCC burden and provide evidence to inform best surveillance intervals. MethodsWe analyzed data from 53 CDH1-GPV carriers who underwent PTG prospectively recruited between Aug 2004 and Aug 2024 (PTG dataset) and a separate cohort of 94 CDH1 CDH1-GPV carriers with [&ge;]2 surveillance endoscopies (endoscopy dataset). Targeted biopsies (TB) and systematic random biopsies (RB) were obtained using the Cambridge protocol. Multivariable negative binomial regression was used to assess the association of clinical (age, family history, CDH1 variant type) and endoscopic factors (mean number of positive TB and RB per endoscopy) with SRCC burden in PTG specimens. A logistic regression model with significant predictors was trained to classify patients into low and high SRCC burden. Temporal trends in biopsy findings were analyzed using linear mixed-effects models, and pathological outcomes at 6-, 12- and 24-month intervals were compared in endoscopy dataset. ResultsOf the 53 patients, 89% had early-stage cancer (pT1aN0M0) and 11% had no cancer (pT0N0M0). The number of SRCC foci ranged from 0 to 273 (median 33, IQR 2-37). The number of positive targeted (P = 0.003) and random biopsies (P < 0.001) during endoscopy surveillance were independent predictors of SRCC burden in the PTG specimen, whereas age, CDH1 mutation type (truncating vs. non-truncating), number of 1st and 2nd degree relatives (SDRs) were not significantly associated. In the endoscopy surveillance cohort, the number of positive biopsies remained largely stable over time, showing fluctuations rather than consistent progression; no significant temporal increase in biopsy positivity was detected over time (P = 0.177) with stable number of SRCC foci at follow-up. Extending surveillance intervals from 6 to 12 or 24 months did not significantly alter progression detection rates. ConclusionEndoscopic surveillance using targeted and random biopsies by experienced endoscopists provides a reliable estimate of SRCC burden in HDGC. Our findings suggest that extending surveillance intervals in patients with low early SRCC burden is clinically safe.

IntroductionEosinophilic oesophagitis (EoE) is a chronic, immune-mediated disease characterized by oesophageal dysfunction and mucosal eosinophilia. Conventional therapies, including dietary elimination, proton pump inhibitors, and topical corticosteroids, are often insufficient or associated with relapse, highlighting the need for targeted treatments. Biologic agents modulating type 2 inflammation have emerged as promising options. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of biologics in EoE. MethodsElectronic databases (PubMed, Embase, CENTRAL, Web of Science, Scopus) and trial registries were searched from inception to [insert date]. Eligible studies were double-blind RCTs comparing biologics with placebo in EoE. Data extraction and risk-of-bias assessment (RoB 2.0) were performed independently by two reviewers. Pooled analyses were conducted using random-effects models, reporting log odds ratios (OR) or risk ratios (RR) with 95% confidence intervals (CIs). Certainty of evidence was rated with GRADE. ResultsA total of 1,706 patients (1,046 males and 696 females; mean age 56.1 {+/-} 15 years; mean follow-up 9.2 months) from 14 randomized controlled trials were included, with 982 patients receiving biologics and 723 assigned to placebo. Biologics significantly increased histological remission compared with placebo (log OR 1.57, 95% CI 0.55-2.60; I{superscript 2} = 89.6%), with benralizumab and lirentelimab demonstrating the strongest effects, while dupilumab showed variable histological outcomes but consistent symptomatic benefits in pivotal trials. Symptomatic response did not improve significantly overall (log OR 0.18, 95% CI -0.73-1.09), although benralizumab showed benefit and lirentelimab trended negatively. Endoscopic remission was not significantly different between biologics and placebo (log OR -0.38, 95% CI -1.56-0.79). Safety analyses revealed no overall increase in adverse events (log RR -0.10, 95% CI -0.40-0.19), with etarsimod and reslizumab associated with fewer events, while lirentelimab suggested a possible increase in cardiological adverse events. Neurological adverse events were infrequent and comparable to placebo. ConclusionBiologic therapies are effective in achieving histological remission in EoE, with benralizumab, lirentelimab, and dupilumab showing the greatest promise. Symptomatic and endoscopic benefits are less consistent, underscoring the need for standardized outcome measures. Biologics were generally safe, with no overall increase in adverse events. These findings support the expanding role of biologics in EoE management while highlighting the importance of long-term and head-to-head trials to optimize therapeutic strategies.

BackgroundThe prevalence and significance of digestive manifestations in COVID-19 remain uncertain. MethodsConsecutive patients hospitalized with COVID-19 were identified across a geographically diverse alliance of medical centers in North America. Data pertaining to baseline characteristics, symptomatology, laboratory assessment, imaging, and endoscopic findings from the time of symptom onset until discharge or death were manually abstracted from electronic health records to characterize the prevalence, spectrum, and severity of digestive manifestations. Regression analyses were performed to evaluate the association between digestive manifestations and severe outcomes related to COVID-19. ResultsA total of 1992 patients across 36 centers met eligibility criteria and were included. Overall, 53% of patients experienced at least one gastrointestinal symptom at any time during their illness, most commonly diarrhea (34%), nausea (27%), vomiting (16%), and abdominal pain (11%). In 74% of cases, gastrointestinal symptoms were judged to be mild. In total, 35% of patients developed an abnormal alanine aminotransferase or total bilirubin level; these were elevated to less than 5 times the upper limit of normal in 77% of cases. After adjusting for potential confounders, the presence of gastrointestinal symptoms at any time (odds ratio 0.93, 95% confidence interval 0.76-1.15) or liver test abnormalities on admission (odds ratio 1.31, 95% confidence interval 0.80-2.12) were not independently associated with mechanical ventilation or death. ConclusionsAmong patients hospitalized with COVID-19, gastrointestinal symptoms and liver test abnormalities were common but the majority were mild and their presence was not associated with a more severe clinical course

BackgroundDolichocolon (DC) is an underrecognized anatomic variant associated with constipation; its association with pediatric ulcerative colitis (UC) is unknown. MethodsWe retrospectively reviewed abdominal MRI and CT scans in pediatric UC, Crohns disease (CD), and non-IBD controls, classifying DC subtypes in 111 cases. ResultsDC prevalence was higher in UC than CD or controls. Type 1 DC predominated in proctitis/left-sided UC (E1/E2), while Type 2 DC was enriched in extensive/pancolitis (E3/E4). Complex DC (Types 1+2) was observed only in UC. DiscussionDC may modify UC distribution independent of constipation, representing a potential developmental modifier of pediatric UC phenotype and a nidus for prevention. Graphic abstractCreated with BioRender by D. Berens

Background and rationale. Digestive diseases are common and lead to significant morbidity, mortality, and health care utilization. We used national survey and claims databases to expand on earlier findings and investigate current trends in the digestive disease burden in the United States. Methods. The National Ambulatory Medical Care Survey, Nationwide Emergency Department Sample, National Inpatient Sample, Vital Statistics of the U.S., Surveillance, Epidemiology, and End Results Program, Optum Clinformatics(R) Data Mart, and Centers for Medicare and Medicaid Services Medicare 5% Sample databases were used to estimate medical care, mortality, cancer incidence, and claims-based prevalence with a digestive disease diagnosis. Rates were age-adjusted (for national databases) and shown per 100,000 population. Results. For all digestive diseases, prevalence (claims-based, all-listed diagnoses) was 30.5% among commercial insurance enrollees (2020) and 53.1% among Medicare beneficiaries (2019). In the U.S. population, digestive diseases contributed to approximately 126 million ambulatory care visits (2015), 41 million emergency department visits (2018), 16 million hospital discharges (2018), and 472,000 deaths (2019) annually. Prevalence, medical care, and mortality rates with a digestive disease diagnosis were higher among children and younger adults (except for emergency department visits) and then increased with age. Women had higher prevalence and medical care rates with a digestive disease diagnosis, but mortality rates were higher among men. Prevalence and medical care rates with a digestive disease diagnosis were higher among Blacks, followed by Whites, then Hispanics, and lowest among Asians. Mortality rates were higher among Blacks compared with Whites and lower among Hispanics compared with non-Hispanics. Between 2004 and the most recent year, ambulatory care visit rates with a digestive disease diagnosis increased by 4%, hospital discharge rates decreased by 3%, and mortality rates decreased by 7%. Among commercial insurance enrollees, rates were higher compared with national data for ambulatory care visits and hospital discharges, but lower for emergency department visits. The medical care use and mortality burdens varied among individual digestive diseases. Conclusion. The digestive disease burden in the United States is substantial, particularly among Blacks and older adults.

ObjectivesGastric emptying testing (GET) assesses gastric motility, however is non-specific and insensitive for neuromuscular disorders. Gastric Alimetry(R) (GA) is a new medical device combining non-invasive gastric electrophysiological mapping and validated symptom profiling. This study assessed patient-specific phenotyping using GA compared to GET. MethodsPatients with chronic gastroduodenal symptoms underwent simultaneous GET and GA, comprising a 30-minute baseline, 99mTC-labelled egg meal, and 4-hour postprandial recording. Results were referenced to normative ranges. Symptoms were profiled in the validated GA App and phenotyped using rule-based criteria based on their relationships to the meal and gastric activity: i) sensorimotor; ii) continuous; and iii) other. Results75 patients were assessed; 77% female. Motility abnormality detection rates were: GET 22.7% (14 delayed, 3 rapid); GA spectral analysis 33.3% (14 low rhythm stability / low amplitude; 5 high amplitude; 6 abnormal frequency); combined yield 42.7%. In patients with normal spectral analysis, GA symptom phenotypes included: sensorimotor 17% (where symptoms strongly paired with gastric amplitude; median r=0.61); continuous 30%; other 53%. GA phenotypes showed superior correlations with GCSI, PAGI-SYM, and anxiety scales, whereas Rome IV Criteria did not correlate with psychometric scores (p>0.05). Delayed emptying was not predictive of specific GA phenotypes. ConclusionsGA improves patient phenotyping in chronic gastroduodenal disorders in the presence and absence of motility abnormalities with improved correlation with symptoms and psychometrics compared to gastric emptying status and Rome IV criteria. These findings have implications for the diagnostic profiling and personalized management of gastroduodenal disorders. Study Highlights1) WHAT IS KNOWN O_LIChronic gastroduodenal symptoms are common, costly and greatly impact on quality of life C_LIO_LIThere is a poor correlation between gastric emptying testing (GET) and symptoms C_LIO_LIGastric Alimetry(R) is a new medical device combining non-invasive gastric electrophysiological mapping and validated symptom profiling C_LI 2) WHAT IS NEW HERE O_LIGastric Alimetry generates a 1.5x higher yield for motility abnormalities than GET C_LIO_LIWith symptom profiling, Gastric Alimetry identified 2.7x more specific patient categories than GET C_LIO_LIGastric Alimetry improves clinical phenotyping, with improved correlation with symptoms and psychometrics compared to GET C_LI

MessageGastric per oral endoscopic myotomy (GPOEM) is a promising therapy for refractory gastroparesis, but patient selection remains challenging. We evaluated body surface gastric mapping (BSGM) phenotypes to predict treatment response. Patients were recruited at Kings College Hospital (Nov 2022-July 2025). BSGM comprised 30-min fasting, standardized nutrient drink with oatmeal bar (482 kcal), and 4-h postprandial recording. Success was defined as [&ge;]1 point reduction in Gastroparesis Cardinal Symptom Index or complete symptom resolution at follow-up. Overall, 53% responded, including all patients with dysrhythmic or continuous phenotypes. Higher gastric frequencies predicted non-response (p=0.03).

BackgroundLuminal application of 5-HT4 receptor agonists can increase peristalsis in the guinea pig, mouse, rat and rabbit colon. Our aim in the present study was to test the effects of intraluminal prucalopride on motor patterns in the human colon. MethodsColonic motor patterns were studied in vivo in a healthy volunteer using High-Resolution Colonic Manometry (HRCM) with an 84-sensor water perfused catheter with 1cm spacing. 5-HT and 5-HT4 receptor immunohistochemistry was performed on human tissue biopsies throughout the colon. Key resultsActivating mucosal 5-HT4 receptors via intraluminal prucalopride enhanced propulsive motor activity in the human colon by increasing occurrence and amplitude of propulsive motor patterns including high-amplitude propagating pressure waves (HAPWs), pancolonic simultaneous pressure waves (SPWs) and HAPW-SPWs. Prucalopride-induced motor patterns had a close temporal association with a significant degree of anal sphincter relaxation and some were accompanied by a strong urge to defecate. Biopsies showed 100% colocalization of the 5-HT4 receptor to enterochromaffin cells throughout the colon and rectum. Conclusions and inferencesActivating luminal 5-HT4 receptors on enterochromaffin cells by intraluminal prucalopride increased propulsive motor activity. 5-HT4 receptors were found only on enterochromaffin cells and not ubiquitous on all epithelial cells. Our data support incorporation of prucalopride in colon-specific drug delivery systems as a prokinetic to treat colonic hypomotility disorders. 50 word abstractHigh-resolution colonic manometry and biopsy immunohistochemistry revealed that 5-HT4 receptors in the lumen of the human colon are present exclusively on enterochromaffin cells and that the 5-HT4 agonist prucalopride evokes all major propulsive motor patterns, associated with significant anal sphincter relaxation, when given intraluminally. 250-character clinical messageActivating luminal 5-HT4 receptors on enterochromaffin cells by intraluminal prucalopride increased propulsive motor activity in the human colon. Colon-specific delivery systems with a 5-HT4 agonist may become the preferred colon prokinetic.

Background/ObjectiveThere is a paucity of data on the management of gastrointestinal (GI) bleeding in patients with COVID-19 amid concerns about the risk of transmission during endoscopic procedures. We aimed to study the outcomes of conservative treatment for GI bleeding in patients with COVID-19. MethodsIn this retrospective analysis, 24 of 1342 (1.8%) patients with COVID-19, presenting with GI bleeding from 22 April to 22 July 2020, were included. ResultsThe mean age of patients was 45.8{+/-}12.7 years; 17 (70.8%) were males; upper GI (UGI) bleeding: lower GI (LGI) 23:1. Twenty-two (91.6%) patients had evidence of cirrhosis-21 presented with UGI bleeding while one had bleeding from hemorrhoids. Two patients without cirrhosis were presumed to have non-variceal bleeding. The medical therapy for UGI bleeding included vasoconstrictors-somatostatin in 17 (73.9%) and terlipressin in 4 (17.4%) patients. All patients with UGI bleeding received proton pump inhibitors and antibiotics. Packed red blood cells (PRBCs), fresh frozen plasma and platelets were transfused in 14 (60.9%), 3 (13.0%) and 3 (13.0%), respectively. The median PRBCs transfused was 1 (0-3) unit(s). The initial control of UGI bleeding was achieved in all 23 patients and none required an emergency endoscopy. At 5-day follow-up, none rebled or died. Two patients later rebled, one had intermittent bleed due to gastric antral vascular ectasia, while another had rebleed 19 days after discharge. Three (12.5%) cirrhosis patients succumbed to acute hypoxemic respiratory failure during hospital stay. ConclusionConservative management strategies including pharmacotherapy, restrictive transfusion strategy, and close hemodynamic monitoring can successfully manage GI bleeding in COVID-19 patients and reduce need for urgent endoscopy. The decision for proceeding with endoscopy should be taken by a multidisciplinary team after consideration of the patients condition, response to treatment, resources and the risks involved, on a case to case basis.