Neurogastroenterology and Motility最新文献

Background: Intestinal ischemia affects the functioning of the Enteric Nervous System (ENS). Pannexin-1 channel participates in cell communication and extracellular signaling. Probenecid (PB) is a pannexin-1 channel inhibitor, which can be a potential treatment for intestinal ischemia.

Aim: Study the effects of ileal ischemia and reperfusion (I/R) and PB treatment on myenteric neurons and in rats.

Methods: Male Wistar rats were used for I/R induction, the ileal vessels were occluded for 45 min and reperfusion was performed after this time. The Sham groups underwent all surgical procedures without obstruction of the ileal vessels. Animals were euthanized 24 h or 14d post-I/R. The PB group received an injection of PB post-I/R. Ileal segments were collected for immunofluorescence analyses to identify neurons calretinin immunoreactive (-ir) and pannexin-1-ir. Neuronal density (cells/field), area (μm²), intestinal motility, and ultrastructural analyses were performed.

Key results: The pannexin-1 channel was double-labeled with calretinin-ir neurons. Neuronal density reduced by 21% reduction in calretinin-ir neurons in the I/R 24 h group and recovered 26% in the PB 24 h group. In the 14d group, there was a 23% reduction in calretinin-ir neurons in the I/R 14d group and a recovery of 26% in the PB 14d group. The analysis of the contraction after electrical simulation was lower in the I/R 14 d group and recovered in the PB 14d.

Conclusions and inferences: Intestinal I/R affects myenteric neurons and causes morphological and functional changes. PB was able to attenuate the effects of I/R and could constitute a therapeutic tool for intestinal I/R.

Introduction: High-resolution manometry (HRM) allows assessment of esophagogastric junction (EGJ) disruption. While type 3 EGJ predicts definitive gastroesophageal reflux disease (GERD), type 2 EGJ is less clearly implicated in GERD pathogenesis. This study aimed to characterize physiologic findings in type 2 EGJ to determine if the HRM-based Milan Score can define GERD within type 2 EGJ.

Methods: 535 patients with suspected GERD who underwent HRM and reflux monitoring were retrospectively analyzed. Clinical, HRM, and reflux study data were compared between the EGJ morphology subtypes, with objective GERD defined according to Lyon Consensus 2.0. The Milan Score, a novel metric that integrates ineffective esophageal motility, EGJ-contractile integral, EGJ morphology, and straight leg raise response, was abnormal when ≥ 137 (risk rate 50% for GERD). Receiver operating characteristic (ROC) curve analysis was performed to assess the accuracy of the Milan Score to predict objective GERD.

Results: Type 3 EGJ was associated with the highest rate of objective GERD, followed by type 2 and type 1 EGJ (p < 0.001), with a corresponding stepwise increase in AET from type 1 to 3 EGJ (p < 0.001). Type 2 EGJ with Milan Score < 137 resembled type 1 EGJ (objective GERD in 23.6% vs. 33.2%, p = 0.09), and type 2 EGJ with score ≥ 137 resembled type 3 EGJ (objective GERD in 88.2% vs. 78.8%, p = 0.11). On ROC analysis, the Milan Score had an area under the curve of 0.858.

Conclusion: While type 2 EGJ includes varying GERD severity, the Milan Score can segregate patients at risk for objective GERD.

Background: Irritable Bowel Syndrome (IBS) is a prevalent condition characterized by dysregulated brain-gut interactions. Despite its widespread impact, the brain mechanism of IBS remains incompletely understood, and there is a lack of objective diagnostic criteria and biomarkers. This study aims to investigate brain network alterations in IBS patients using the functional connectivity strength (FCS) method and to develop a support vector machine (SVM) classifier for distinguishing IBS patients from healthy controls (HCs).

Methods: Thirty-one patients with IBS and thirty age and sex-matched HCs were enrolled in this study and underwent resting-state functional magnetic resonance imaging (fMRI) scans. We applied FCS to assess global brain functional connectivity changes in IBS patients. An SVM-based machine - learning approach was then used to evaluate whether the altered FCS regions could serve as fMRI-based markers for classifying IBS patients and HCs.

Results: Compared to the HCs, patients with IBS showed significantly increased FCS in the left medial orbitofrontal cortex (mOFC) and decreased FCS in the bilateral cingulate cortex/precuneus (PCC/Pcu) and middle cingulate cortex (MCC). The machine-learning model achieved a classification accuracy of 91.9% in differentiating IBS patients from HCs.

Conclusion: These findings reveal a unique pattern of FCS alterations in brain areas governing pain regulation and emotional processing in IBS patients. The identified abnormal FCS features have the potential to serve as effective biomarkers for IBS classification. This study may contribute to a deeper understanding of the neural mechanisms of IBS and aid in its diagnosis in clinical practice.

Confocal laser endomicroscopy (CLE) is a novel technique allowing real time in vivo microscopy during standard endoscopy. Recently, acute mucosal alterations after food administration visualized by CLE have been linked to symptoms in irritable bowel syndrome (IBS). Interestingly, the observed reactions occurred in subjects without demonstrable allergic sensitization to food-this is in line with mechanistic research showing local but not systemic allergic sensitization to foods in an animal model for IBS. Here, European experts conducting CLE with food administration provide a narrative review of the available literature and propose practical guidance on the use of this technique. CLE allows physicians to observe acute mucosal reactions after the application of food to the duodenal mucosa in patients with functional gastrointestinal disorders. Some open-label interventions show a symptomatic benefit when patients exclude the nutrient that triggered an acute mucosal reaction. However, many technical, mechanistic, and clinical questions remain unanswered to date. Technically, the interobserver variability and learning curve requires systematic evaluation and criteria or cutoffs for alterations require validation. Mechanistic studies are needed to enhance our understanding of the mechanisms underlying observed alterations. Finally, rigorous blinded controlled studies are needed to assess a link of these observed alterations with symptom generation. CLE offers a platform allowing scientific insights related to food induced acute mucosal alterations. However, many questions remain unanswered, and more research is warranted to understand the role of acute mucosal alterations visualized upon food administration in IBS pathophysiology and treatment.

Background: Internationally adopted Chicago Classification (CC) criteria based on adult normative data have been used to diagnose children with esophageal motility disorders undergoing high-resolution esophageal manometry (HREM). The aim of this study was to compare HREM parameters of children without dysphagia and children with dysphagia and normal findings according to CC.

Methods: HREM metrics of 41 children (13.2 (9-18) years; 20 female) without dysphagia and 41 children (13.7 (8-18) years; 30 female) with dysphagia and normal diagnosis according to CC were compared. Analyzed data included resting and integrated relaxation pressures (IRP) of upper (UES) and lower (LES) esophageal sphincters, esophageal peristaltic contractile integrals, transition zone (TZ) gaps, distal latency (DL), and manometric esophageal length to height ratio (MELH). 95%ile normative cutoffs were calculated from the cohort without dysphagia.

Key results: Proximal contractile integral (PCI), UES and LES mean resting and IRP were not significantly different between the cohorts (p > 0.3). On the contrary, distal contractile integral (DCI), TZ gap and MELH were notably different with p = 0.0002, p = 0.027, and p = 0.033 respectively. According to 95%ile normative cutoffs of DCI, TZ gap and MELH, in cohort with dysphagia 27%, 15%, and 22% of patients respectively were not normal.

Conclusion & inferences: First study ever to compare HREM parameters of children without dysphagia to children with dysphagia. Considerable proportion of children with dysphagia may be underdiagnosed according to the adult criteria. This emphasizes the need for universally accepted child-specific diagnostic protocols and norms.

Background: Dysphagia is one of the most common complaints that gastroenterologists encounter in the outpatient setting. To evaluate this common complaint, patients are often sent for a barium esophagram, a test that is widely available, inexpensive, and easy to perform. This simple test provides a reliable method to evaluate esophageal anatomy and structural abnormalities.

Purpose: This narrative reviews the history of the development and validation of the timed-barium esophagram (TBE), along with its strengths and limitations, and discusses its use in the pre- and posttreatment assessment of patients with achalasia, esophagogastric junction outflow obstruction (EGJOO), and esophageal strictures. Providing excellent anatomic detail of the esophagus and an accurate assessment of esophageal emptying, over time, the TBE has become part of the standard workup in our Swallowing Center for patients with dysphagia.

Background: Patients' report of bowel movement consistency is unreliable. We demonstrate the feasibility of long-term automated stool image data collection using a novel Smart Toilet and evaluate a deterministic computer-vision analytic approach to assess stool form according to the Bristol Stool Form Scale (BSFS).

Methods: Our smart toilet integrates a conventional toilet bowl with an engineered portal to image feces in a predetermined region of the plumbing post-flush. The smart toilet was installed in a workplace bathroom and used by six healthy volunteers. Images were annotated by three experts. A computer vision method based on deep learning segmentation and mathematically defined hand-crafted features was developed to quantify morphological attributes of stool from images.

Key results: 474 bowel movements images were recorded in total from six subjects over a mean period of 10 months. 3% of images were rated abnormal with stool consistency BSFS 2 and 4% were BSFS 6. Our image analysis algorithm leverages interpretable morphological features and achieves classification of abnormal stool form with 94% accuracy, 81% sensitivity and 95% specificity.

Conclusions: Our study supports the feasibility and accuracy of long-term, non-invasive automated stool form monitoring with the novel smart toilet system which can eliminate the patient burden of tracking bowel forms.

Background: Functional diarrhea (FDr) is a common disorder in toddlers and adults. In children, the Rome criteria define FDr as a disorder of children younger than 5 years old exclusively. However, in clinical practice, school-aged children and adolescents sometimes consult for symptoms that mimic the diagnosis of FDr. We conducted a study aimed at assessing the prevalence of FDr in school-aged children and adolescents.

Methods: A cross-sectional study was conducted in children aged 8-18 years from two schools in Colombia. Children completed self-report validated questionnaires to diagnose disorders of gut-brain interaction (DGBI) per Rome IV (QPGS-IV) for their age group and the questions related to FDr from the Rome IV questionnaire for infants and toddlers.

Key results: After excluding children with organic diseases and IBS-D, 981 participants were included (female 53.8%, White 24.7%, Indigenous 10.9%, mixed race 52.6%). Of the 981 participants, 325 (33.1%) had a DGBI. Of these, 17 children (5.2%) were diagnosed with FDr (3 participants 8-12 years; 14 participants 13-18 years). FDr was more prevalent among White children compared to non-White children (mixed race, Black, and Indigenous) (p = 0.01).

Conclusion & inferences: Despite the absence of FDr in the Rome IV criteria for children and adolescents, 1.7% of children aged 8-18 years likely have FDr. This study suggests that FDr does occur in children and adolescents. If confirmed in future studies, the diagnosis of FDr should be considered for inclusion in future editions of the Rome criteria for children of all ages.

Introduction: The 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).

Methods: The 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.

Results: ANMS 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.

Conclusion: The 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.