Neurogastroenterology & Motility

Background & Aims: The association between upper gastrointestinal (GI) symptoms and delayed gastric emptying time (GET) is debated. This study utilized Body Surface Gastric Mapping (BSGM) and the 'Auckland Classification' BSGM phenotyping scheme to investigate whether symptom associations with GET vary across different mechanistic phenotypes. Methods: A pooled analysis was performed on two prospective datasets of 194 patients with chronic upper GI symptoms. Participants underwent simultaneous BSGM (Gastric Alimetry) and gastric emptying testing (breath test or scintigraphy). Validated time-of-test symptom profiling was recorded at 15-minute intervals using 0-10 Likert-type scales. Patients were classified: 'Spectral Abnormal' (abnormal electrophysiology), 'Sensorimotor' (symptoms correlate with gastric electrical amplitude), 'Continuous' (symptoms uncorrelated), and 'NA' (no phenotype). Results: In the analyzed cohort, 24% had delayed GET. Overall, delayed GET was associated with a higher total symptom burden (15.6 delayed vs. 8.8 normal, p=0.006; r=0.30, p<0.001), specifically postprandial fullness (p=0.004) and early satiation (p=0.015). However, associations varied significantly by phenotype. In the 'Sensorimotor' phenotype, nausea was associated with delayed GET (4.9 vs. 1.0, p=0.027; r=0.59, p=0.009), while total symptom burden was 23.3 vs. 8.4 (p=0.135). Conversely, patients with 'Continuous' or 'Spectral Abnormal' phenotypes, or who were unclassified, showed no symptom associations. Conclusions: Delayed GET is weakly associated with an increased burden of upper GI symptoms. However, gastroduodenal disorders are heterogeneous, such that phenotyping reveals this association to be exclusive to patients with a 'Sensorimotor' phenotype. These results could improve targeting of therapies that address gastric emptying.

Introduction: Illness perceptions, the cognitive and emotional beliefs patients hold about their condition, are key determinants of patient outcomes across a range of chronic health conditions. Although well-studied in several gastrointestinal disorders, their role remains poorly characterized within patients with functional dyspepsia (FD) and chronic nausea and vomiting syndrome (CNVS). This study examined the associations between illness perceptions, gastrointestinal symptoms, mental health, and gastric electrophysiology in these patients. Methods: Patients meeting self-reported Rome IV criteria for FD and/or CNVS underwent body surface gastric mapping (BSGM) using Gastric Alimetry (Alimetry, New Zealand). The standardized protocol included a 30-minute fasting baseline, 482 kCal meal, and a 4-hour postprandial recording, with concurrent symptom logging. From the BSGM data, patients were phenotyped using established rule-based criteria via the Auckland Classification. Illness perceptions were assessed using the Brief Illness Perceptions Questionnaire alongside validated psychological and quality of life metrics. Results: The cohort included 309 patients (80% female; median age= 36, 15-88) who reported highly negative illness perceptions, which were significantly correlated with worse symptomatology, quality of life, and mental health (medium-large effect sizes). Using multivariable analysis, perceived consequences and emotional responses emerged as the most robust predictors of these patient-reported outcomes. Additionally, illness perceptions significantly mediated the relationship between mental health and gastrointestinal symptoms, with large effect sizes. Associations with gastric electrophysiology were limited to BMI-Adjusted Amplitude, which was associated with poorer perceptions of treatment control and greater emotional response to symptoms. Furthermore, the Continuous Phenotype (normal spectral activity, with continuous symptoms) was associated with worse illness perceptions, including higher perceived consequences, symptom identity, concern, and emotional response, whilst the High Frequency Phenotype was associated with lower understanding. Discussion: The way patients perceive their condition is a quantifiable aspect of the illness experience that is associated with symptom burden, mental health, and quality of life in patients with FD and CNVS. The observed associations with gastric electrophysiology suggest that illness perceptions may also vary in relation to underlying patient physiology. These findings support the consideration of illness perceptions as part of multidisciplinary assessment and management, including targeted patient education and clinical interventions to address distressing or maladaptive illness beliefs.

Background: Functional dyspepsia (FD) is among the most common gastrointestinal disorders worldwide and is characterized by symptoms including epigastric pain, early satiety, postprandial fullness, bloating, and upper abdominal discomfort. Itopride hydrochloride is commonly administered as 50 mg three times daily (TID). To improve convenience and potentially enhance adherence, a once-daily (OD) 150 mg extended-release formulation was developed. Phase 1 studies demonstrated bioequivalent overall exposure between the OD and TID regimens, with sustained-release characteristics and no evidence of dose dumping, supporting advancement to Phase 3. This pivotal clinical study evaluated whether itopride hydrochloride 150 mg OD is non-inferior to the established 50 mg TID regimen in improving FD symptoms over 8 weeks. Methods: This Phase 3, randomized, open-label, multicenter, active-controlled study enrolled 564 participants with FD (or chronic gastritis) to compare the efficacy and safety of itopride hydrochloride 150 mg OD versus 50 mg TID over 8 weeks. The primary endpoint was change in overall FD severity from baseline to Week 8, assessed using the Leeds Dyspepsia Questionnaire (LDQ) severity score. Secondary endpoints included symptom-specific severity, disease-specific quality of life, responder rates, treatment acceptance, and safety. Results: Clinical non-inferiority in terms of overall FD severity was demonstrated with OD treatment compared to TID. LDQ severity improved by -9.60 (95% CI -10.15, -9.05) with TID and -9.76 (95% CI -10.32, -9.19) with OD, with a between-group difference of 0.16 (95% CI -0.42, 0.74). Improvements across symptom domains and quality of life measures were comparable. Treatment acceptance favored OD (mean 4.22 vs 3.83; p < 0.001). Both regimens were well tolerated, with predominantly mild adverse events. This clinical evaluation of OD was supported by the Phase 1 results confirming that both single-dose and multiple-dose administration of itopride hydrochloride 150 mg OD provided a comparable extent of exposure to the 50 mg TID regimen, demonstrated by area under the curve (AUC) values within the 80 to125% bioequivalence range and stable pharmacokinetic profiles across fed and fasted conditions. Conclusion: The study confirmed that itopride hydrochloride 150 mg OD is non-inferior to the TID regimen for improving FD (or chronic gastritis) symptoms. The OD regimen demonstrated comparable efficacy, favorable treatment acceptance, and a positive benefit-risk profile, offering a more convenient therapeutic option for patients.

BackgroundObjective tools for longitudinal dietary monitoring, despite its importance in the health triad of diet, sleep, and exercise, remain limited. Widely available ambulatory options include continuous glucose monitoring, which is a delayed response, and manual logging, which is rife with human error. Clinical tools such as gastric emptying scintigraphy are impractical for everyday use. High-resolution electrogastrography (HR-EGG) offers an alternative by treating gastric myoelectric activity as a biomarker of digestive state. However, its utility for ambulatory meal detection remains unclear. We hypothesize that HR-EGG and accelerometry together encode distinct postprandial gastric signatures to enable automated meal detection, and that postural context represents a relevant source of variation in signal detectability. MethodsHR-EGG and accelerometry data were collected from seven healthy adults across sixteen 150-minute meal sessions under IRB-approved protocol. Each session included a 30-minute fasted baseline, consumption of a standardized meal, and 90-minute postprandial period of sitting, walking, and lying in a randomized order. Features of the gastric slow wave, including raw and normalized bandpower, phase gradient directionality (PGD), wave direction, and wave speed, were extracted alongside triaxial accelerometer magnitude. A dilated one-dimensional convolutional network (1D CNN) was trained to classify meal consumption at five-minute resolution using leave-one-subject-out cross-validation. Postural effects on gastric myoelectric metrics were assessed using the Friedman test. ResultsThe model achieved a mean AUROC of 0.925 (95% CI: [0.857, 0.993]) and mean AUPRC of 0.824 (95% CI: [0.668, 0.980]; null model: 0.20). Feature ablation showed PGD as the most informative input ({Delta}AUPRC = -0.188), with wave propagation speed the least informative ({Delta}AUPRC = -0.105). Walking produced the highest signal-to-noise ratio (9.94 dB), lying had the most stable gastric rhythm (89.1% normogastric), and sitting demonstrated the greatest frequency instability (dominant frequency standard deviation = 0.825 cpm). ConclusionA dilated 1D CNN applied to spatiotemporal HR-EGG features enables temporally aware passive meal detection across ambulatory contexts. This study framework addresses a gap between clinical need for objective dietary monitoring and the limitations of current detection methods.

Background: Sleeve gastrectomy is the most frequently performed bariatric procedure worldwide but is associated with the development of de novo gastroesophageal reflux disease (GERD). Hiatal hernia has been identified as a relevant anatomical factor in postoperative reflux, although most studies evaluate it dichotomously without analyzing whether its size influences GERD risk. The aim was to evaluate the association between preoperative hiatal hernia size and de novo GERD after sleeve gastrectomy. Methods: Retrospective, single - center, observational study of patients undergoing sleeve gastrectomy at Hospital Central Norte de Petroleos Mexicanos (2018 - 2025). Demographic and clinical characteristics, endoscopic classification of hiatal hernia size (small <2 cm, medium 2.1 - 4 cm, large >4 cm), and evidence of de novo GERD were analyzed using descriptive statistics, Fisher's exact test, odds ratio (=R) estimation with 95% confidence intervals (CI), and binary logistic regression. Statistical significance was set at p<0.05. Results: Fiftysix patients were included (mean age 48.3 {+/-} 8.1 years; 67.9% male). Hiatal hernia classification was conclusive in 46 patients (82.1%): 63.0% no hernia, 4.3% small, 30.4% medium, and 2.2% large. De novo GERD occurred in 14.0% of patients without preexisting GERD (6/43). No significant association was found between hiatal hernia size and de novo GERD (Fisher p=0.515). In the reduced logistic model, neither hiatal hernia (medium/large vs. absent/small; OR 3.47; 95% CI 0.50 - 29.43; p=0.207) nor age (OR 1.02; 95% CI 0.90 - 1.13; p=0.754) was significantly associated. No evaluated factor (sex, smoking, alcohol, age) reached significance. Conclusions: In this cohort, no statistically significant association was demonstrated between preoperative hiatal hernia size and de novo GERD after sleeve gastrectomy; however, the low number of events limits the ability to exclude a clinically relevant association. These findings are compatible with a multifactorial mechanism rather than with the isolated presence of this finding. Prospective studies with larger sample sizes and standardized reflux assessment instruments are required to confirm these results.

Body surface gastric mapping (BSGM) enables non-invasive measurement of gastric electrophysiology, but the signals are approximately 100 times weaker than cardiac potentials and overlap spectrally with motion artifacts, necessitating labor-intensive manual review that limits clinical scalability. We present an uncertainty-aware deep learning framework combining a signal reconstruction network with a parallel uncertainty estimation network to automate artifact correction in high-resolution BSGM. Models were trained on 2,398 multihour, 64-channel recordings from 27 international clinical sites using weak supervision, a physiology-aware loss function, and uncertainty-gated quality control. In an independent cohort of 127 patients, the system achieved relative reductions of 39% in signal reconstruction error, 9% in total data removed, and 23% in amplitude--movement correlation compared with the industry-standard Wiener filter. Improved signal fidelity altered automated clinical phenotyping in 7% of patients by recovering previously obscured gastric rhythms. Uncertainty-aware deep learning enables reliable automated artifact correction in body-surface gastric mapping, improving signal fidelity and enabling scalable clinical interpretation. The system is FDA-cleared (510(k) K252504) and deployed in clinical practice, demonstrating that data-driven artifact correction can meet regulatory requirements for medical devices and reduce dependence on specialist manual review.

Introduction Individuals with Gastroesophageal Reflux Disease (GERD) often experience airway inflammation and bronchoconstriction as a result of reflux aspiration and/or vagally mediated reflexes. The Impulse Oscillometry System (IOS) is a sensitive, non-invasive tool that can detect subtle changes in airway resistance. While there are few studies exploring airway resistance in GERD globally, no studies have been conducted in Sri Lanka. Therefore, we aim to compare the airway resistance using IOS in medical undergraduates with and without symptomatic GERD. Methods A cross-sectional study was conducted among 811 medical undergraduates (31.1% male; mean age 22.9 years) at the Faculty of Medicine, Rajarata University of Sri Lanka. Symptomatic GERD was screened using the validated GerdQ, and a cutoff of[&ge;]8 was used to diagnose those with GERD symptoms. Of the 242 (29.8%) with GERD symptoms, 188 with chronic respiratory diseases or recent respiratory symptoms were excluded, and 50 with GERD symptoms and 50 healthy, age- and sex-matched controls were recruited. Lung function was assessed using IOS and spirometry, according to American Thoracic Society (ATS) and European Respiratory Society (ERS) guidelines. Results Prevalence of symptomatic GERD among medical undergraduates was 29.8% (242/811). The common symptoms among GERD were heartburn (89.6%, 217/242) and regurgitation (85.5%, 207/242). Oscillometry parameters including, R5-R20 Hz (15.29% vs 9.69%, p=0.002), Fres (14.95 1/s vs 13.37 1/s, p = 0.04), and AX (0.66 vs 0.48, p = 0.02) were significantly higher in students with symptomatic GERD (mean = 15.29%) than in healthy controls (mean = 9.69%; p = 0.002). However, spirometry parameters including FEV1, FVC, and PERF did not differ between the GERD-positive and control groups. Conclusion Individuals with symptomatic GERD demonstrated a higher peripheral airway resistance compared to controls, whereas no significant difference was observed in upper airway resistance. This could be due to the gastric acid stimulation of vagal nerve terminations in the lower part of the esophageal wall, leading to increased resistance in the peripheral airways through vagally mediated bronchoconstriction.

Gut-brain communication has emerged as a rapidly expanding field of research, with recent electrophysiological studies revealing rhythmic gut-brain coupling between gastric activity and brain oscillations in humans. Gut motility is a key determinant of gastrointestinal function, but it remains unclear whether individual differences in gut motility reflected by weekly bowel movements (e.g., defecation frequency) are associated with differences in gut-brain coupling. Here, we address this question by examining women with self-reported daily bowel movements (N = 38) and women with less frequent bowel movements (N = 38). We recorded simultaneous electroencephalography (EEG) and electrogastrography (EGG) at fasting state, performed cognitive assessments, and analysed faecal short-chain fatty acids (SCFAs) as markers of colonic fermentation. In a subset of participants, EEG-EGG coupling was assessed twice over an interval of at least eight weeks to assess test-retest reliability. In this group, EEG-EGG coupling showed moderate test-retest reliability (Intraclass Correlation Coefficient (ICC) = 0.50). When comparing the two groups of women, the phase-amplitude coupling (PAC) analysis between EEG and EGG signals revealed a significantly stronger gut-brain coupling in women with daily bowel movements compared to women with less frequent bowel movements (p = 0.03). We additionally found that women with daily bowel movements made less errors in the cognitive tasks and had higher levels of faecal SCFAs. A path analysis suggested that bowel movements significantly affect gut-brain phase-amplitude coupling through faecal SCFAs. However, neither faecal SCFAs nor phase-amplitude coupling significantly predicted cognitive performance, suggesting the existence of alternative pathways for the association between bowel movements and cognitive performance. Together, our findings suggest that the strength of gut-brain coupling is associated with bowel movements and cognitive performance, making EEG-EGG coupling a promising marker of human gut-brain interactions.

ObjectiveTo establish a standardized training program for endoscopic pathogen visualization literacy (EPVL) based on fluorescence rapid on-site evaluation (ROSE) technology for gastroenterologists, and to evaluate its training efficacy. MethodsA prospective quasi-experimental study was conducted. A total of 54 gastroenterology trainees were non-randomly allocated into the EPVL training group (Group A, n=28, 16-hour comprehensive training) and the control group (Group B, n=26, 3.5-hour traditional teaching). Pre- and post-training assessments included theoretical examinations, fluorescence ROSE image interpretation tests (30 parallel images per set), interpretation speed measurement, and clinical decision-making integration evaluation. The primary outcome was the change in image interpretation accuracy, analyzed by ANCOVA with pre-test scores as the covariate. ResultsBaseline characteristics were comparable between groups (P>0.05 for all demographic variables and pre-test scores). Group A showed significant improvement in image interpretation accuracy from 57.8{+/-}13.6% pre-training to 82.5{+/-}11.2% post-training (improvement of 24.7%, paired t=-12.86, P<0.001), while Group B improved from 58.5{+/-}13.0% to 71.0{+/-}13.5% (improvement of 12.5%, paired t=-5.24, P<0.001). After ANCOVA adjustment for pre-test scores, the between-group difference was significant (F(1, 51)=10.95, P=0.0017, 2=0.177), with Cohens d=0.94 (large effect size). Interpretation speed in Group A (19.2{+/-}2.8 s/image) was significantly faster than in Group B (32.5{+/-}6.0 s/image, t=-10.45, P<0.001). Clinical decision-making scores were significantly higher in Group A (80.5{+/-}8.0 vs. 65.3{+/-}11.5, t=5.60, P<0.001). The Kappa agreement with the gold standard in Group A improved from 0.56{+/-}0.18 to 0.84{+/-}0.11 (t=-8.35, P<0.001). Participant satisfaction exceeded 88%. ConclusionThe EPVL training program significantly improves gastroenterologists fluorescence ROSE image interpretation accuracy, speed, and clinical decision-making integration, providing a novel and effective standardized training paradigm for digestive endoscopy education.

Objective: Circadian rhythms are frequently disrupted in patients in the intensive care unit (ICU), potentially worsening clinical outcomes. Continuous enteral nutrition throughout the day and night is common in the ICU, but eliminates feeding-fasting cycles that serve as important timing cues for the circadian system. The objective of this study was to determine the effect of providing enteral nutrition in a cyclic daytime pattern, compared with continuous administration, on circadian rhythmicity in critically ill patients in the ICU. Design: Single-center randomized controlled trial Setting: Mixed medical-surgical tertiary intensive care unit in the Netherlands Patients: Adult ICU patients ([&ge;]18 yr) receiving enteral nutrition. Intervention: Patients were randomized to receive either continuous, or cyclic daytime enteral feeding (08:00-20:00), initiated from the start of nutritional support. Measurements and Main Results: Sixty-two ICU patients were enrolled, of whom 51 were included in the per-protocol analysis. While the amplitude of the 24-hour rhythm in core body temperature did not differ significantly between the cyclic daytime and continuous feeding groups (0.17 [interquartile range: 0.09-0.24] vs. 0.20 [0.13-0.30], p=0.182), the 24-hour rhythm in heart rate was enhanced in patients receiving cyclic daytime feeding, as reflected by significantly higher amplitudes and more synchronized peak times. No significant differences in 24-hour rhythmicity were observed between groups for the other vital signs or melatonin. Conclusions: Our findings suggest that cyclic daytime feeding may strengthen circadian rhythms in critically ill patients. Further studies are warranted to evaluate its impact on clinical outcomes.

BackgroundTranscutaneous auricular vagus nerve stimulation (taVNS) depends on activating afferent vagal pathways, leading to central and physiological (parasympathetic) modulation. Explaining how taVNS changes cardiorespiratory physiology requires systematic characterization of the effects of electrode location and stimulation waveform using rigorous experimental controls. ObjectiveTo determine the acute effects of four taVNS stimulation configurations (left unilateral 25 Hz, 100 Hz, burst, and bilateral 25 Hz) on physiological markers of parasympathetic activation compared with configuration-matched earlobe stimulation in healthy subjects at rest. MethodsCustomized 8-mm ear-clip electrodes delivered monophasic 500 s pulses (anode anterior) to the tragus or a configuration-matched earlobe control across four stimulation configurations (left unilateral 25 Hz, 100 Hz, burst, and bilateral 25 Hz). Twenty-five healthy participants completed a randomized, single-blind, within-subject crossover study, undergoing both active and control stimulation for all four configurations (200 sessions total). Each session consisted of five 60-second stimulation blocks (1,000 stimuli total). Heart rate (HR), heart rate variability (HRV; RMSSD), and respiration were recorded continuously. Linear mixed-effects models compared physiological responses between tragus and earlobe stimulation during the first stimulation block (primary analysis), across 5-second HR intervals (secondary analysis), and averaged across all five stimulation blocks (post hoc analysis). ResultsDuring the first stimulation block, HRV was significantly higher during unilateral left 25 Hz tragus stimulation than during the matched earlobe control ({beta} = -10.34, t(33) = -2.63, p = .01, 95% CI [-18.05, -2.64]), consistent with increased parasympathetic activity. No significant differences were observed for HRV with the other stimulation configurations, or for HR or respiration under any configuration. Analysis of 5-second HR intervals likewise revealed no significant temporal effects for block one. Analysis of 5-second heart rate intervals across the five blocks identified differences between tragus and earlobe at discrete time points but did not show a consistent temporal pattern across the stimulation period. Across all five stimulation blocks, unilateral left 25 Hz tragus stimulation remained associated with higher HRV ({beta} = -6.56, t(124) = -3.85, p < .01, 95% CI [-9.90, -3.22]) and also produced an increase in HR relative to earlobe stimulation ({beta} = -1.05, t(24) = -2.57, p = .01, 95% CI [-1.85, -0.24]). Respiration was unaffected throughout. ConclusionIn this systematic study, unilateral left 25 Hz tragus stimulation produced physiological modulation consistent with vagal target engagement. These findings underscore the importance of rigorous dose-specific taVNS studies to establish reproducible physiological biomarkers.

Central Amygdala neurons expressing Isl1 (CeAIsl1+) project to brainstem regions involved in control of the jaw and the stomach, including the parabrachial nucleus (PBN), the nucleus of the tractus solitary (NTS), and the parvocellular reticular nucleus (PCRt). Stimulation of CeAIsl1+ cells elicits fictive feeding, particularly biting. Activation of these neurons can rate dependently set the amplitude of bite force and inhibition dramatically reduces bite force. Findings suggest this force generation depends on modulation of a jaw closing reflex involving tooth sensory neurons in the mesencephalic trigeminal nucleus (Me5). Anatomical tracing studies show Me5 neurons receive synaptic input from CeAIsl1+ neurons. Patch clamp recordings of Me5 neurons indicate this synapse is mediated by GABA yet depolarizing. Activation of CeAIsl1+ neurons is capable of dramatically potentiating the periodontal jaw closing reflex, a reflex whereby Me5 tooth sensory neurons activate jaw closing muscles. In addition to controlling the actions of the jaw, CeAIsl1+ neuron stimulation is sufficient to reduce gastric pH. Inhibition experiments show these cells are necessary for lowering gastric pH in mice anticipating a meal. Finally, CeAIsl1+ neurons can modulate gastric motility, stimulation transiently suppresses gastric motility, an effect also observed when animals chewed food. Subdiaphragmatic vagotomy eliminated the transient suppression of gastric motility otherwise observed with CeAIsl1+ neuron stimulation or food chewing. Taken together, this molecularly and anatomically defined population generates specific motor patterns of ingestion that involve not only release of oromotor patterns, but also modulation of gastric functions.

Aims To develop the Bowel Irrigation Questionnaire (BIQ), a patient-reported experience measure (PREM) designed to assess the user experience of transanal irrigation (TAI). Methods Statements were generated through literature review and qualitative interviews with healthcare professionals (HCPs) and product users. Statements were rated on a 6-point content validity index scale through an international three-round online Delphi survey by 20 expert panel members. Consensus attainment was defined based on percentage agreement, statements which did not meet consensus were discussed at a final international online consensus meeting. The content validity of the PREM was evaluated through cognitive interviews and the Questionnaire on Questionnaires (QQ-10). Reliability was assessed using a test-retest design, where users completed the BIQ on two occasions one week apart. Results 215 statements were generated from 9 multi-disciplinary qualitative interviews and literature review. Statements were refined to reduce repetition and ensure clarity. 73 statements grouped into 11 domains were reviewed through the Delphi survey. Following the Delphi survey and clinical consensus meeting, the preliminary BIQ consisted of 15 items. Six cognitive interviews were conducted, resulting in a finalised BIQ of 16 items. 32 product users completed both the QQ-10 and test-retest study, the results of which demonstrated good content validity and temporal stability respectively. Conclusions The Bowel Irrigation Questionnaire is a novel PREM designed to assess the user experience of TAI in both clinical and research settings. The instrument demonstrates good validity, acceptability and temporal stability, supporting its use as a reliable measure of patient experience.

Background The Low Anterior Resection Syndrome (LARS) score is an internationally validated instrument for identifying bowel dysfunction following anterior resection for rectal cancer. Although widely used, it has been shown to have limited sensitivity for capturing the impact of LARS on daily-life and response to treatment. We have therefore developed a novel patient-reported outcome measure (PROM): the LARS Impact and Consequences Assessment Tool (LARS-ICAT). Methods Initial development of LARS-ICAT followed a five-stage process following established PROM development guidance. Stage one established the conceptual foundation through previously published Delphi consensus. Stage two involved item generation, followed by evaluation of content validity through patient focus groups (n=11) in stage three. Stage four comprised iterative expert review and refinement through clinical consensus with patient involvement. Stage five involved cognitive interviews with patients conducted across five rounds (n=23). Results Several items identified through the Delphi consensus were reworded as they included multiple concepts. A one-month recall period was selected, with six and four response options for symptom and consequence items respectively. Additional consequence items, including impact on sleep and transport use, were incorporated. Focus groups and clinicians emphasised the importance of capturing individual symptom burden, leading to the addition of symptom bother scales. These iterative refinements culminated in LARS-ICAT v2.6. Conclusions LARS-ICAT is a novel PROM designed to assess symptom burden and treatment response in LARS. Future studies will assess its psychometric properties. Once validated, LARS-ICAT will provide a comprehensive, patient-centred assessment of LARS, enhancing our ability to manage this challenging condition.

Background: Endoscopic submucosal dissection (ESD) of superficial esophageal squamous cell carcinoma (SESCC), with or without the esophageal gland duct involvement (DI or NDI), has been reported in small case series, but ESD-related safety, efficacy, and outcomes remain unknown. We conducted a retrospective study of those issues in consecutive 748 patients treated at our center in China. Material and Methods: Over the study period from January 2014 to January 2019, we identified 748 eligible SESCC patients who were divided into the DI (22.6%, 169/748) and NDI (77.4%, 579/748) groups, based on histopathologic reports. Following the European and Japanese guidelines on endoscopic resection of SESCC, we investigated and statistically compared characteristics of clinicopathology and ESD-related safety, efficacy, and prognosis between DI and NDI groups. Results: The mean age of patients was 64.9 years for the cohort and significantly older in the DI (66.1) than in the NDI (64.5) group (P<0.05). There was no significant difference in smoking/alcohol abuse and comorbidity. Endoscopically, the DI group showed significantly larger tumor size and deeper invasion than the NDI group. There was no ESD-related death in the cohort. Although the en bloc resection rate was 100%, the complete and curative resection rates were significantly lower in the DI (88.2% and 61.2%, respectively) than in the NDI (96.4%, and 86.9%, respectively) group (P<0.01). ESD-related infection (0.7%) and bleeding (2.3%) rates were very low and no significant difference was found between the two groups. Only one perforation (0.1%) occurred in the NDI group. Post-ESD stenosis was 11.9% for the cohort and significantly more common in the DI (20.7%) than in the NDI (9.3%) group (P<0.01). The overall survival rate was 95.7% for the cohort and significantly lower in the NDI (94.6%) than in the DI (100.0%) group (P<0.05). However, there was no significant difference in disease-specific death, recurrence-free survival, distant metastasis, and the requirement for subsequent chemoradiation therapy and surgery between the two groups. Conclusion: In our cohort, there was no ESD-associated death; ESD-related infection and bleeding were minimal; and perforation was rare. Post-ESD stenosis was 11.9% in prevalence and successfully managed by endoscopic dilation. The overall survival rate was 95.7%. Compared to the NDI group, the DI group showed older age, larger tumor size, deeper invasion, lower complete and curative resection rates, higher prevalence of post-ESD stenosis; there was no significant difference in disease-specific death. Taken together, ESD was safe with excellent efficacy and prognosis for endoscopic resection of SESCC with or without esophageal gland duct involvement. Keywords: superficial esophageal squamous cell carcinoma, endoscopic submucosal dissection, ductal involvement, survival, postoperative stenosis.

Serotonin (5-HT) is a monoamine which regulates not only central functions but also various peripheral functions. Peripheral 5-HT is primarily derived from the gut, and its synthesis and secretion are regulated by enterochromaffin cells. Stimulation of enterochromaffin cells by food factors may regulate mental functions via the gut-brain axis. We studied whether oleuropein, an olive-derived polyphenol, regulates central functions by stimulating 5-HT secretion from enterochromaffin cells. In QGP-1 cells, which are enterochromaffin-like cells, 10 {micro}M oleuropein stimulated 5-HT secretion via Ca2+ influx through T-type and L-type voltage-dependent Ca2+ channels. Hydroxytyrosol, a metabolite of oleuropein, also promoted 5-HT secretion via the same mechanism. Furthermore, oleuropein stimulated 5-HT secretion from isolated mouse colon via voltage-dependent Ca2+ channels. Finally, oral administration of 200 mg/kg oleuropein acutely increased the depression-like behavior in the mice, which was inhibited by the prior administration of ramosetron, a 5-HT3 receptor antagonist. These findings suggest that oleuropein is a potent stimulant of gut 5-HT secretion, and show that food factors may act to regulate mental function via the secretion of gut 5-HT.

Importance Sleep-disordered breathing (SDB) is common in childhood and is associated with attentional and behavioral impairments despite largely preserved sleep macrostructure and minimal abnormalities in conventional electroencephalographic measures. This discrepancy has contributed to the perception that sleep is relatively preserved in pediatric SDB and has limited understanding of the physiological mechanisms underlying morbidity. Objective To determine whether pediatric SDB is associated with disruption of the regional organization and homeostatic dynamics of slow-wave activity (SWA), a key physiological marker of sleep-dependent neural recovery and development. Design, Setting, and Participants Cross-sectional study of 62 children aged 4 to 12 years who underwent overnight polysomnography with high-density electroencephalography in a laboratory setting. Participants were recruited from clinical referrals and the community, spanning the full spectrum of SDB severity. Exposures SDB severity indexed by hypopnea index (HI), apnea-hypopnea index (AHI), and obstructive apnea index (OAI). Main Outcomes and Measures Regional electroencephalogram-derived SWA (0.5 to 4 Hz) topography and exponential decay parameters derived from frontal and posterior cortical regions. The frontal-to-posterior decay-rate ratio was evaluated as a summary measure of regional sleep homeostasis. Results In children with lower hypopnea index, SWA demonstrated the expected developmental pattern, with posterior predominance in younger children and a progressive shift toward a more balanced anterior-posterior distribution with age. Increasing HI was associated with attenuation or reversal of this spatial organization. Global SWA showed no meaningful association with SDB severity. In contrast, regional frontal and posterior decay parameters were strongly associated with HI (adjusted R2 = 0.53; p < 1e-6) but not OAI (adjusted R2 = 0.05; p = .95). The frontal-to-posterior decay-rate ratio showed the strongest association with HI {beta} = 4.15; 95% CI, 3.17-5.13; p < 1e-10; adjusted R2 = 0.55. Conclusions and Relevance Pediatric SDB was associated with regional disruption of slow-wave sleep homeostasis rather than global loss of deep sleep. These alterations affected both the spatial organization and temporal dynamics of SWA during a period of active cortical maturation and were not captured by conventional sleep metrics. Regional SWA dynamics may provide a developmentally sensitive marker of physiological disease burden in children with SDB.

Background Optimal timing for resuming direct oral anticoagulants (DOACs) after high-risk endoscopic procedures remains uncertain, and existing recommendations derive largely from expert opinion. The objective of this study was to characterize practice patterns and perceptions among endoscopists and outcome prioritization among patients with atrial fibrillation, in order to inform the design of the planned RESUME randomized trial. Methods We conducted parallel, cross-sectional surveys of practicing endoscopists and patients with atrial fibrillation using electronic questionnaires administered via Qualtrics. The endoscopist survey, distributed through the American Society for Gastrointestinal Endoscopy, assessed practice patterns, acceptability of early (postoperative day [POD] +1), intermediate (POD +3), and late (POD +5) resumption strategies, and perceptions of clinical equipoise. The patient survey, distributed through two advocacy organizations, assessed perceived confidence in existing guidance and prioritization of bleeding versus thromboembolic risk. Results A total of 201 endoscopists and 477 patients (92.5% taking a DOAC) provided evaluable responses. Endoscopists demonstrated wide variability in preferred timing of DOAC resumption after a standardized high-risk mucosal resection vignette, ranging from same-day resumption to delays beyond five days. POD +2 was the most commonly selected strategy, and most respondents rated more than one proposed RESUME trial arm as acceptable. Nearly all endoscopists (98.9%) rated a randomized trial to determine optimal timing as important. Patient preferences regarding bleeding versus stroke risk were heterogeneous and symmetrically distributed around the neutral response on a five-point ordinal scale. Preferences did not differ by prior stroke or transient ischemic attack, prior major bleeding, age, sex, or geographic region. More than half of patients (54.6%) reported being very or somewhat confident that clear guidance exists regarding DOAC resumption, despite the absence of high-quality randomized evidence informing this question. Conclusions Endoscopists demonstrate substantial practice variability and clinical equipoise, and patients demonstrate heterogeneous and balanced outcome preferences, regarding the timing of DOAC resumption after high-risk endoscopy. These findings support the ethical justification and relevance of the planned RESUME trial.

Background and AimsActive capsule endoscopy could advance gastrointestinal diagnostics by enabling controlled navigation beyond passive peristalsis. However, current systems are often limited by inefficient propulsion, high power demands, or reliance on external actuation. Herein, we designed, developed and evaluated a novel electromagnetic impact-actuated capsule endoscope incorporating a ferromagnetic rail-enhanced locomotion mechanism. MethodsThe capsule employed an internal electromagnetic actuator comprising a movable coil-armature assembly guided along a ferromagnetic rail and surrounded by permanent magnets. Controlled current pulses generated reciprocating motion and propulsion through momentum transfer. Bench-top testing using a deformable intestinal model assessed locomotion and power consumption. Ex-vivo experiments were subsequently performed in porcine intestine under dry and physiologically simulated wet conditions. Transit speed, power consumption, and system stability were recorded. ResultsBench-top testing demonstrated stable propulsion at speeds up to 8.5 mm/s with a mean power consumption of 84 mW. During ex-vivo evaluation, mean capsule velocities were 1.95 mm/s and 7.2 mm/s under dry and wet conditions, respectively. Average power consumption was 96 mW and 193 mW. The actuator maintained reliable locomotion while preserving a compact system volume of [~]6.19 cm3. Lubricated conditions, representative of the intestinal environment, resulted in enhanced propulsion efficiency despite a concomitant increase in instantaneous power consumption. ConclusionThe electromagnetic impact-actuated capsule demonstrated reliable locomotion in biologically relevant ex-vivo environments while maintaining compact dimensions and moderate power requirements. Ferromagnetic rail-enhanced flux concentration offers a promising propulsion strategy for future actively navigated and therapeutic capsule endoscopy platforms.

Abstract Background : Helicobacter pylori infection remains a significant public health concern and a leading cause of peptic ulcer disease (PUD). This organism colonizes the gastric mucosa and often remains asymptomatic until complications develop. Despite its global prevalence, the magnitude and association between H. pylori infection and PUD are not well established in many community settings, including Dar es Salaam. This study aimed to determine the fecal prevalence of H. pylori, risk factors, and the correlation between H. pylori and PUD in adults clinically suspected of PUD in Dar es Salaam Communities, 2025. Methodology: A cross-sectional, community-based study was conducted among 390 adults clinically suspected of having PUD in Dar es Salaam over a two-month data-collection period (April-June 2025). Sociodemographic, environmental, behavioral, and clinical data were collected using structured questionnaires, and stool samples were analyzed for Helicobacter pylori antigen using standard methods. The primary outcome was Helicobacter pylori infection status, while the secondary outcome was associated risk factors and their correlation with clinical suspicion of PUD. Data were analyzed using SPSS version 25, with categorical variables expressed in frequencies and percentages. Associations were assessed using chi-square tests and multivariable logistic regression, with results reported as adjusted odds ratios and 95% confidence intervals. Spearmans rank correlation was used to assess the relationship between H.pylori infection and clinical suspicion of PUD. Of the 400 adults enrolled,390(97.5%) provided complete data and were included in the analysis Results: Of 390 participants, 252 (64.6%) were female, and the mean age was 36.9 {+/-} 15.7 years. A total of 161 individuals (41.3%) tested positive for H. pylori. Higher Infection rates were observed among adults aged 40-49 years (46.7%), singles (44.6%), those consuming tap water (46.9%), residents of crowded area//s (43.2%), and individuals who consumed alcohol and smoked (50.4% and 44.5%, respectively). Only the source of drinking water showed a significant association with H. pylori infection. A positive correlation was observed between H. pylori infection and clinically suspected PUD. Conclusion: H.pylori infection was common among adults clinically suspected of PUD in the Dar es Salaam communities. The use of tap water for drinking was identified as the most significant risk factor. These findings highlight the need for routine community-based screening and public health interventions to improve water safety and reduce transmission. Future studies should employ longitudinal designs to establish causal relationships between H. pylori infection, behavioral risk factors, and clinical outcomes.