Citations

ABSTRACT Introduction Chronic gastroduodenal disorders remain challenging to manage, and new diagnostic approaches are needed to better delineate underlying causes and guide therapeutic decisions. Body Surface Gastric Mapping (BSGM) technologies combine high‐resolution gastric myoelectrical activity measurements with symptom and psychological profiling to provide mechanistic insights into gastric motor and sensory dysfunction. An International Working Group convened to derive the first consensus classification of BSGM phenotypes (the “Auckland Classification”). Methods A Technical Group conducted a systematic literature and clinical database review to identify objective test biomarkers and candidate disease mechanisms. Evidence was synthesized across 50 studies (primarily in gastroparesis, chronic nausea and vomiting, and functional dyspepsia), and BSGM phenotypes were mapped to existing treatment guidelines. Subsequently, iterative review and development of consensus was performed by a Consensus Group composed of international clinical experts familiar with BSGM. Eleven statements underlying the classification were then derived and circulated as a final survey to establish agreement. Results Six BSGM phenotypes were endorsed: three defined by myoelectrical abnormalities (Dysrhythmic, High Frequency, and Low Meal Response) and three by characteristic symptom associations (Sensorimotor, Continuous, and Delayed Onset Symptoms). Published studies plausibly linked these phenotypes to mechanisms including interstitial cell of Cajal depletion, vagal impairment, hypomotility, visceral hypersensitivity, gut‐brain dysregulation, and small bowel dysfunction. Phenotypes were also mapped to existing mechanism‐based treatment guidelines. Ten out of the eleven statements had > 80% agreement. Conclusions The Auckland Classification, derived by international consensus, presents a structured framework for BSGM‐defined patient phenotypes. Evidence and mechanism‐based treatment options are suggested for each phenotype to provide a foundation for research, further validation, and a pathway for integrating BSGM into clinical care.

Abstract Sex differences in cancer outcome, including that of glioblastoma (GBM), are shaped by biological, hormonal, and immunological factors and impact disease progression, treatment responses, survival, and tumor microenvironment (TME) interactions. Platelets regulate the immune responses and tumor progression in many cancers, but it is not clear how they contribute to these sex-based differences by affecting the dynamics of the TME. Here, we show that GBM patients exhibit heightened platelet reactivity driven by PAR4 signaling. In murine GBM models, both pharmacological inhibition of PAR4 using BMS986120 and genetic deletion of PAR4 significantly prolong survival in females but not males. This survival advantage is estrogen dependent: it is preserved in chromosomal male-hormonal female mice within the four-core genotype model and is rescued in ovariectomized mice treated with estrogen. The survival benefit is TME specific and is mediated by platelet-driven enhancement of CD8⁺ T cell infiltration into the tumor. Inhibition of platelet PAR4 signaling increases calcium signaling through an estrogen-dependent interaction between PAR4 and estrogen receptor β (ERβ)—a receptor interaction not previously described. PAR4-activated platelets within the TME suppress CD8⁺ T cell function, and depletion of CD8⁺ T cells abolishes both the tumor-induced platelet reactivity and the survival benefit conferred by PAR4 inhibition. These findings establish platelet-mediated PAR4 signaling as a critical driver of tumor progression and identify sex-specific immune responses as key to therapeutic efficacy.

Gastrointestinal (GI) defects pose a significant clinical challenge, impacting patient outcomes and healthcare costs. Endoscopic closure techniques have emerged as effective and minimally invasive approaches to manage these defects. This review explores the various endoscopic techniques, including over-the-scope clips (OTSC), endo suturing systems, through-the-scope (TTS) clips, and the X-Tack system. Each technique offers distinct advantages and limitations, making it suitable for specific clinical scenarios. While these devices have demonstrated promising results in clinical practice, further research is needed to optimize their use and address knowledge gaps. Large-scale randomized controlled trials are essential to establish evidence-based guidelines for device selection and procedural techniques. By embracing technological advancements and addressing research limitations, the field of endoscopic closure devices has the potential to revolutionize GI care, leading to improved patient outcomes and expanded therapeutic possibilities.

INTRODUCTION: Bloating, distention, and gas-related gastrointestinal (GI) symptoms are frequently reported by patients across the spectrum of disorders of gut-brain interaction (DGBI). We aimed to characterize these using latent class modeling in a large multinational survey. METHODS: A nationwide survey of adults in the United States, United Kingdom, and Mexico used quota sampling for demographic balance. It included Rome IV diagnostic questions, Intestinal Gas Questionnaire, Patient Health Questionnaires for anxiety and depression (PHQ-4) and somatization (PHQ-12), quality of life (PROMIS Global-10), and lifestyle questions. Latent class analysis was performed using “depmix” in RStudio 4.2.3. RESULTS: A total of 3,471 subjects experiencing bloating and/or distention (mean age 43 years, 57% female) were included. Using 42 demographic and pertinent clinical variables, latent class analysis revealed 6 distinct clusters. The first 2 clusters demonstrated limited-to-moderate impairment in health-related quality of life (HRQoL), with both characterized by some degree of dietary and supplement associations; however, cluster 2 lacked specific triggers observed in other clusters. The subsequent 2 clusters showed favorable HRQoL and mild gas-related symptoms, with only cluster 4 exhibiting distinct dietary triggers. The final 2 clusters, associated with bowel dysfunction, showed a higher prevalence of irritable bowel syndrome (IBS) with constipation and IBS mixed in cluster 5, and IBS with diarrhea in cluster 6. These bowel dysfunction clusters exhibited severe gas symptoms in the preceding 24 hours and greater HRQoL impairment compared with the other 4 clusters. Notably, cluster 5 was linked to dietary triggers, whereas cluster 6 was defined by psychosocial comorbidities. DISCUSSION: Bloating and distention patients are likely driven by variable influences of dietary, psychological, and bowel dysfunction. Further studies are needed to identify mechanisms and titrate treatment suited to specific mechanistic drivers.

ABSTRACTBackgroundData are limited on the natural history and symptom patterns of cyclic vomiting syndrome (CVS), a disorder of gut–brain interaction characterized by recurrent stereotypical vomiting, retching, and nausea episodes.MethodsA 6‐month, observational, remote study prospectively assessed symptom patterns in adults with CVS using an electronic daily diary. Patients recorded their disease experience, including CVS symptoms and associated severity, in the daily diary. The study defined a CVS episode start as the first day of 5 or more vomiting and/or retching (V + R) events. Episode end was defined as the first day of ≥ 7 (prespecified main analysis) or ≥ 4 (sensitivity analysis) days without any diary V + R events.Key ResultsEighty‐eight of 93 (94.6%) enrolled patients (62 female; mean age, 37.7 years) had daily diary data recorded during the study; 61 (69.3%) patients had at least one episode. In the prespecified main analysis, 191 episodes (median, 0.6 per 30 diary days) were reported (median duration, 3.0 days); 17.8% of the episodes lasted > 10 days. In the sensitivity analysis, 248 episodes (median, 0.7 per 30 diary days) were reported (median duration, 2.0 days). Thirteen of 88 (14.8%) patients with diary data had interepisodic V + R (reported V + R events without meeting the threshold for study‐defined episode). Other CVS‐related (non‐V + R) symptoms (most frequently nausea, abdominal pain, and sweating) were reported more frequently during the episode versus the interepisodic period.Conclusions and InferencesThis prospective longitudinal study shows marked heterogeneity of CVS episodes and highlights the need to better define and characterize episodes in these patients.

AbstractIntroductionThe American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index‐Daily Diary (ANMS GCSI‐DD) is a patient‐reported outcome (PRO) instrument for gastroparesis. This study evaluated the psychometric properties of the ANMS GCSI‐DD and determined a meaningful change threshold using the data from a phase 2b trial in adults with moderate‐to‐severe idiopathic or diabetic gastroparesis (DG).MethodsThe psychometric properties of ANMS GCSI‐DD were analyzed using other clinician‐ and patient‐reported outcomes from 242 patients during the 12‐week trial. Trial exit interviews were conducted in a cohort of 32 patients to capture their perspectives on meaningful change from the trial.ResultsANMS GCSI‐DD demonstrated good performance: unidimensionality scores exhibited good fit; internal consistency reliability was >0.70; test–retest reliability was above 0.90, and convergent validity showed strong correlations (0.70–0.90) with overall severity rating and moderate correlations (0.30–0.70) with other outcomes. ANMS GCSI‐DD scores discriminated among groups with varying severity of gastroparesis symptoms in known‐groups validity (p < 0.001) and were responsive to symptom improvement. Triangulation of the quantitative anchor‐based estimates of 0.9–1.4 category points as a meaningful change in the ANMS GCSI‐DD composite score, and the qualitative exit interview findings of 0.5–1.5 as meaningful change, supports a one‐point change on a five‐point scale (0–4) as the meaningful change threshold.ConclusionThe ANMS GCSI‐DD is a reliable and valid PRO instrument to employ in clinical development for patients with moderate‐to‐severe idiopathic or DG, and a one‐point score change in the ANMS GCSI‐DD composite score is recommended as a meaningful change threshold of symptom change.

AbstractThe role of long‐term parenteral support in patients with underlying benign conditions who do not have intestinal failure (IF) is contentious, not least since there are clear benefits in utilising the oral or enteral route for nutritional support. Furthermore, the risks of long‐term home parenteral nutrition (HPN) are significant, with significant impacts on morbidity and mortality. There has, however, been a recent upsurge of the use of HPN in patients with conditions such as gastro‐intestinal neuromuscular disorders, opioid bowel dysfunction, disorders of gut–brain interaction and possibly eating disorders, who do not have IF. As a result, the European Society of Clinical Nutrition and Metabolism (ESPEN), the European Society of Neuro‐gastroenterology and Motility (ESNM) and the Rome Foundation for Disorders of Gut Brain Interaction felt that a position statement is required to clarify – and hopefully reduce the potential for harm associated with – the use of long‐term parenteral support in patients without IF. Consensus opinion is that HPN should not be prescribed for patients without IF, where the oral and/or enteral route can be utilised. On the rare occasions that PN commencement is required to treat life‐threatening malnutrition in conditions such as those listed above, it should only be prescribed for a time‐limited period to achieve nutritional safety, while the wider multi‐disciplinary team focus on more appropriate biopsychosocial holistic and rehabilitative approaches to manage the patient's primary underlying condition.

AbstractBackgroundGastrointestinal dysmotility is frequently suspected in patients with gastroparesis, functional dyspepsia, and ileus, and in the intensive care unit. Monitoring of gastric motility in clinical practice remains challenging. A novel technology was developed to meet the medical need for a widely available bedside tool to monitor gastric motility continuously. The VIPUN™ Gastric Monitoring System (GMS) comprises a nasogastric feeding tube with intragastric balloon to allow for measuring gastric contractions.AimsTo compare the performance of the VIPUN GMS versus a reference technique (manometry).MethodsIn this validation study in healthy subjects, the investigational catheter and a solid‐state manometry catheter were placed in the stomach concomitantly. Motility was recorded for 2.5 h: 2 h in a fasting state, followed by a 400‐kcal liquid meal, and monitoring of the fed state for the remaining half hour. The performance of both systems was compared by automated recognition and manual identification of the contractile activity. Data are presented as mean (standard deviation).Key ResultsThe analysis set comprised 13 healthy subjects (6 women, age: 27.5 (8.1) years, BMI: 22.2 (2.46) kg/m2). Automatically‐recognized contractility was strongly correlated between the two techniques (endpoint: contraction duration; Spearman ρ = 0.96, p < 0.001). A correlation was also observed between the number of individual contractions identified by expert gastroenterologists on both technologies independently (ρ = 0.71, p = .007) and between the contractions identified by the experts and by the GMS software (ρ = 0.87, p = 0.001). No serious or unanticipated adverse events occurred.Conclusions & InferencesThe observed strong correlations with the gold standard, manometry, validate the performance of the VIPUN GMS as a gastric monitoring system.