Neurogastroenterology and Motility最新文献

Background: Certain patients still experience nocturnal reflux symptoms despite taking a standard morning PPI. This study compares the efficacy of adding a wedge pillow versus an evening PPI to the morning PPI for treating nocturnal reflux symptoms.

Methods: This noninferiority randomized trial included patients with ≥ 2/week nocturnal heartburn/regurgitation despite morning PPI use for ≥ 4 weeks. Participants were randomized to either a wedge pillow with morning or twice-daily PPI for 4 weeks. Nocturnal reflux symptoms were assessed using the nocturnal gastroesophageal reflux disease symptom severity and impact questionnaire (NGSSIQ) at Weeks 0, 2, and 4, along with quality of life, daytime sleepiness, and sleep quality. Twenty-four hour pH-impedance monitoring was conducted at baseline and Week 4. Wedge pillow compliance was monitored with a pressure-sensing timekeeper.

Results: Twenty-four patients were enrolled with comparable baseline characteristics and severity of nocturnal reflux. At Week 4, NGSSIQ scores were 30.01 ± 1.97 in the wedge pillow group and 36.33 ± 1.96 in the twice-daily PPI group (mean difference - 6.32; 95% CI -10.28 to 6.21), which falls below the predefined non-inferiority margin demonstrating non-inferiority. Sleep quality was better in the pillow group (5.55 ± 0.56 vs. 7.53 ± 0.60, p = 0.001). Although nighttime median bolus contact time was longer in the twice-daily PPI group [4.3 (2.9-5.4) vs. 7.4 (3.5-15.5) seconds, p = 0.03], other reflux parameters did not show clinically relevant differences between groups. Pillow compliance was high, with 83.3% reporting satisfaction.

Conclusion: Adding a wedge pillow was not inferior to evening PPI for nocturnal reflux symptoms and was associated with greater improvements in sleep quality, despite the absence of clinically relevant differences in reflux parameters, supporting the wedge pillow as a potential alternative for managing nocturnal reflux symptoms.

Trial registration: Thaiclinicaltrials.org: TCTR20240920004.

Introduction: Systemic sclerosis (SSc) is a rare autoimmune disease with near-universal symptoms of gastrointestinal dysmotility. The contribution of disruption of the gut-brain axis to SSc gastrointestinal symptoms is unknown. We aimed to quantify the frequency of SSc patients meeting diagnostic criteria for DGBI-like symptoms.

Methods: In a cross-sectional survey study, the frequency of irritable bowel syndrome (IBS), functional dyspepsia (FD), functional dysphagia and post prandial distress syndrome (PPDS) was assessed using the Rome-IV-Questionnaire. Participants completed a Short Form-36, Health Assessment Questionnaire Disability Index, UCLA Gastrointestinal 2.0 Questionnaire (GIT 2.0), and ScleroID to assess quality of life, daily function, SSc gastrointestinal disease severity, and overall impact of SSc, respectively. The associations between IBS, FD, functional dysphagia, PPDS, and SSc severity, daily function, and quality of life were assessed using linear regression analysis.

Results: Out of 101 participants, 21 met FD criteria, and 18 met IBS criteria. These patients had more severe SSc gastrointestinal disease, measured by total GIT-2.0 scores (IBS coef: 0.69 (0.44-0.95, p < 0.01); FD coef: 0.64 (0.41-0.86, p < 0.01)). FD was associated with poorer physical health-related quality of life (SF-36 PCS coef: 38.70 (28.54-48.66)), and both IBS and FD were associated with a greater overall impact of SSc as measured by the ScleroID (IBS coef: 1.55 (0.35-2.75), p < coef: 1.94 (0.89-2.98, p < 0.001)).

Conclusion: One-fifth of SSc patients surveyed met DGBI diagnostic criteria, suggesting that the presence of disorders of gut-brain interaction should be considered when assessing SSc gastrointestinal disease. Our results indicate that there may be a subgroup of SSc patients who have co-existing DGBI-like symptoms contributing to their clinical presentation of SSc-associated gastrointestinal disease.

Background: Enteroendocrine cells (EECs) are dispersed along the intestinal mucosa and transduce luminal stimuli into hormonal signals. EECs exhibit neuron-like features and express both α-synuclein and tau, two proteins pathologically and genetically linked to Parkinson disease (PD). These observations support the hypothesis that EECs may be involved in disease development in the "body-first" PD subtype. Cellular models represent invaluable tools for studying the role of α-synuclein and tau in PD pathogenesis. However, the sensitivity and specificity of commercial antibodies for detecting α-synuclein and tau in EEC cell lines remain unclear.

Methods: We tested by immunoblot a panel of commercial total-α-synuclein and total-tau antibodies on protein lysates from three EEC cell lines: GLUTag, NCI-H716, and STC-1. Pharmacological and biochemical manipulations were applied to assess the specificity of antibodies against phosphorylated α-synuclein and tau.

Key results: Five antibodies detected total α-synuclein in NCI-H716 lysates, whereas the antibodies D1M9X and Tau12 detected total tau in GLUTag and NCI-H716 lysates, respectively. α-synuclein and tau protein levels were comparable between naïve and differentiated NCI-H716 cells. Four phospho-specific antibodies revealed phospho-α-synuclein S129 in NCI-H716. Of the nine phospho-tau antibodies tested, six recognized tau phosphorylated at specific epitopes (T181, S199, T231, S356, S396, and S404) in GLUTag cells.

Conclusions and inferences: Our results indicate that NCI-H716 cells represent an ideal EEC model for studying α-synuclein expression and phosphorylation, whereas GLUTag cells are preferable for investigating tau protein biology. This work provides a comprehensive antibody toolbox to dissect the physiological and pathological role of α-synuclein and tau in EECs.

Background: Epilepsy is a chronic neurological disorder primarily affecting the central nervous system. However, growing evidence suggests that epilepsy also impacts peripheral organs, including the gastrointestinal tract. The intestinal barrier, essential for maintaining homeostasis and immune defense, is particularly susceptible to oxidative stress, which can disrupt junctional proteins, leading to increased permeability and barrier dysfunction. This study aimed to investigate the effects of epilepsy on duodenal morphology and intercellular junction integrity, as well as to evaluate the potential protective role of Rosa Canina Seed Oil (RSO) in mitigating these alterations.

Methods: A pilocarpine-induced rat model of epilepsy was employed in 47 male Sprague-Dawley rats, randomly assigned to eight experimental groups, and treated intragastrically with Rosa canina seed oil (RSO) at doses of 0.125, 0.25, or 0.5 mL/rat/day prior to epilepsy induction. Histomorphometric analysis was conducted to assess villus height, crypt depth, and mucosal surface area. Immunohistochemical staining was used to evaluate the expressions of key junctional and cytoskeletal proteins, including zonula occludens-1 (ZO-1), E-cadherin, and vimentin. Correlation analysis was performed to explore associations between morphological parameters and protein expression levels.

Results: Epileptic rats exhibited significant reductions in villus height, crypt depth, and absorptive surface area, along with downregulation of ZO-1, E-cadherin, and vimentin, indicating compromised barrier function. RSO treatment demonstrated a dose-dependent protective effect, with moderate and high doses partially restoring intestinal morphology and tight junction integrity. Notably, higher doses of RSO significantly restored ZO-1 levels and preserved vimentin expression, suggesting its role in stabilizing the epithelial barrier and cytoskeletal framework. Correlation analysis confirmed a strong association between epilepsy-induced structural disruptions and barrier dysfunction (p < 0.05), highlighting the potential protective effects of RSO.

Conclusion: These findings demonstrate that epilepsy impairs intestinal barrier integrity by altering epithelial structure and junctional protein expression, leading to increased permeability. RSO treatment partially counteracted these effects, supporting epithelial stability and barrier function in a dose-dependent manner.

Background and aims: Esophagogastric junction (EGJ) integrity influences gastroesophageal reflux disease (GERD) pathophysiology, but its association with positional reflux patterns remains unclear. This study evaluated whether upright and recumbent acid exposure differs based on EGJ status on high-resolution manometry (HRM).

Methods: Retrospective study of patients undergoing HRM and 24-h pH-impedance monitoring off-therapy. EGJ was defined disrupted if any of the following HRM features were present: type II/III morphology, basal pressure < 10.4 mmHg, or EGJ-CI < 9.6 mmHg·cm; intact otherwise. Acid exposure time (AET) and additional reflux metrics were calculated in both positions. Conclusive GERD was defined per Lyon 2.0 (AET > 6%).

Results: Among 283 patients, 102 (36%) had a disrupted EGJ. These patients showed higher total AET (4.7% vs. 1.9% in the intact EGJ, p < 0.001), primarily driven by recumbent exposure (1.9% vs. 0.2%, p < 0.001). In patients with conclusive GERD (n = 91), total and upright AET were similar across EGJ subgroups, while recumbent AET was significantly higher in the disrupted EGJ group (11.5% vs. 3.1%, p < 0.001). Pathologic recumbent AET (> 6%) and severe esophagitis (LA C-D) were observed only in patients with disrupted EGJ (72% vs. 0%, p < 0.001; 14% vs. 0%, p = 0.015, respectively).

Conclusion: EGJ integrity stratifies GERD phenotypes by positional pattern: upright-predominant in patients with intact EGJ and recumbent-predominant in those with disrupted EGJ, the latter also associated with severe esophagitis. This suggests distinct pathophysiologic GERD mechanisms depending on EGJ integrity and may guide personalized management.

Background: Disorders of gut-brain interactions (DGBI) are increasingly prevalent in children and adults and can significantly impact quality of life starting in childhood and extending into adulthood. DGBI encompass a range of gastrointestinal symptoms in the absence of identifiable structural etiologies with biopsychosocial implications. Ongoing research efforts aim to understand the etiology and pathophysiology of DGBI, with disruptions of the gut-brain axis leading to visceral hypersensitivity and hypervigilance believed to be involved in symptom manifestation. Currently, there are 17 pediatric DGBI that are diagnosed via the Rome IV criteria. However, there is a paucity of research evaluating the clinical presentation, diagnosis, and management of pediatric patients with DGBI and concurrent structural gastrointestinal conditions despite the significant symptom overlap and diagnostic challenges.

Purpose: This summative review will aid clinicians by providing an updated overview of pediatric studies assessing the overlap between DGBI and inflammatory bowel disease, celiac disease, and eosinophilic gastrointestinal disorders. Functional abdominal pain, irritable bowel syndrome, and functional constipation are common DGBI subtypes in pediatric patients with underlying structural gastrointestinal disorders. It is imperative that clinicians be cognizant of this overlap, particularly when gastrointestinal symptoms persist despite appropriate management of structural conditions. In such cases, a multidisciplinary approach may be necessary if there is concern for a comorbid DGBI to provide comprehensive care for patients and to improve quality of life, provider satisfaction, and successful clinical outcomes.

Background: The pathophysiology of rumination syndrome is not entirely elucidated. We aimed to assess gastric emptying and fundic accommodation through solid gastric emptying scintigraphy in children with rumination syndrome and explore the relationship between scintigraphic findings and high-resolution impedance esophageal manometry results.

Methods: Gastric retention at 1, 2, 3, and 4 h from standardized meal ingestion were measured. Delayed gastric emptying was defined as gastric retention > 10% at 4 h. The ratio of gastric counts in the proximal stomach to those in the entire stomach measured immediately after meal ingestion (IMD⁰) was used as a marker of fundic accommodation. A value of < 0.568 defined an impaired fundic accommodation. The number of rumination episodes occurring during the first postprandial hour of manometry recording were calculated.

Results: Among 33 children included (median age: 14 years) 10 (30%) had impaired fundic accommodation and 12 (36%) delayed gastric emptying. Children with impaired fundic accommodation have a higher median number of rumination events [10 (IQR 7-12) vs. 6 (IQR 4-89); p = 0.03] recorded during the first postprandial hour. Similarly, at 1-h children with delayed gastric emptying have a higher median number of rumination events [12 (IQR 10-13) vs. 6 (IQR 3-8); p = 0.0004]. The number of rumination events was inversely related to IMD⁰ (p = 0.03; r = -0.4) and directly related to gastric retention at 1-h in the whole stomach (p = 0.003; r = 0.5), fundus (p = 0.03; r = 0.4) and antrum (p = 0.02; r = 0.4).

Conclusion: More than half of children with rumination syndrome included in our study present an abnormal gastric motor function on solid-meal gastric emptying scintigraphy that might contribute to the occurrence of rumination episodes. The detection of these abnormalities might enhance targeted clinical trials and patient management.