Neurogastroenterology and Motility最新文献

Background: A high prevalence of disorders of gut-brain interaction (DGBI) exist in patients with hypermobile Ehlers-Danlos Syndrome (hEDS) and hypermobility spectrum disorders (HSD). However, it is unknown if clusters of hEDS/HSD patients exist which overlap with different DGBIs and whether this overlap influences presence of comorbidities and quality of life. We aimed to study these knowledge gaps.

Methods: A prospectively collected hEDS/HSD cohort of 1044 individuals were studied. We undertook Uniform Manifold Approximation and Projection-enabled (UMAP) dimension reduction to create a representation of nonlinear interactions between hEDS/HSD and DGBIs, from which individuals were stratified into clusters. Somatization, Postural Tachycardia Syndrome (PoTS), autonomic symptoms, psychological factors and quality of life were statistically compared between clusters.

Key results: The mean age of patients was 40 ± 13.2 years; 87.8% were female. Patients segregated into three clusters: Cluster 0 (n = 466): hEDS/HSD+ functional foregut disorders (FFD) + irritable bowel syndrome (IBS); Cluster 1 (n = 180): hEDS/HSD+ IBS and Cluster 2 (n = 337): hEDS/HSD alone. In cluster 0, we demonstrated increased somatization (p <0.0001), anxiety (p <0.0001), depression (p <0.0001), PoTS prevalence (p = 0.003), autonomic symptoms (p <0.0001) and reduced quality of life (p <0.0001) compared to cluster 2. Cluster 0 had greater comorbidity burden than cluster 1.

Conclusions: Within hEDS/HSD, subgroups exist with a high prevalence of FFD and IBS. These subgroups have a higher prevalence of psychological disorders, dysautonomia and poorer quality of life compared with hEDS/HSD alone. Further research should focus on healthcare utilization, management and prognosis in hEDS/HSD and DGBI overlap.

Background: The aims of this study were to confirm the non-inferiority of tegoprazan to lansoprazole up to week 4 in patients with erosive esophagitis (EE) and to evaluate its effectiveness in rapid mucosal healing and symptom relief at week 2.

Methods: In this multi-center, randomized, double-blind, active-comparator non-inferiority trial, 218 patients with endoscopically confirmed EE (Los Angeles Classification Grades A-D) were randomly allocated to either the tegoprazan (50 mg) or lansoprazole (30 mg) group. The primary endpoint was the cumulative proportion of patients with healed EE up to week 4, as confirmed through endoscopy. The proportion of patients with healed EE at week 2 was also evaluated. Furthermore, CYP2C19 genotypes, symptoms, safety, and tolerability were assessed.

Key results: In the full-analysis set, 103 and 109 participants in the tegoprazan and lansoprazole groups, respectively, were analyzed. The cumulative healing rates up to week 4 were 95.2% (98/103) and 86.2% (94/109) (difference [95% confidence interval], 8.91 [1.22-16.59]; p < 0.0001 for non-inferiority and 0.0266 for superiority), while those at week 2 were 88.4% (91/103) and 82.6% (90/109) (5.78 [-3.66-15.22], p = 0.0005 for non-inferiority) for tegoprazan and lansoprazole, respectively. Tegoprazan showed consistent healing rates regardless of CYP2C19 genotypes.

Conclusions and inferences: Tegoprazan was superior to lansoprazole in the treatment of EE up to 4 weeks. Further studies are necessary to confirm these findings and clarify the superiority of tegoprazan, especially in the treatment of severe EE.

Trial registration: ClinicalTrials.gov identifier: NCT05267743.

Background: Oropharyngeal dysphagia is prevalent among neurological patients, often necessitating enteral tube feeding with a nasogastric tube (NGT) or percutaneous endoscopic gastrostomy (PEG). These patients are at significant risk of developing aspiration pneumonia. This study aimed to assess the impact of oropharyngeal dysphagia on pneumonia risk requiring hospitalization in neurological patients on long-term enteral tube feeding.

Methods: This retrospective observational study was conducted between 2015 and 2022. It included neurological patients who underwent upper gastrointestinal endoscopy combined with a Modified Flexible Endoscopic Evaluation of Swallowing (mFEES) for suspect dysphagia, characterized by difficulty or discomfort in swallowing. Participants were either orally fed or had been on long-term enteral tube feeding via NGT or PEG. A 2-year follow-up was conducted to monitor pneumonia cases requiring hospitalization. Multivariate analyses were conducted to identify risk factors for pneumonia requiring hospitalization.

Key results: A total of 226 orally fed and 152 enteral tube-fed patients were enrolled. Multivariate analyses showed a significantly increased risk of pneumonia in patients with a history of pneumonia and those receiving enteral tube feeding. Subgroup analysis indicated a significantly lower risk of pneumonia among enteral tube-fed patients with oropharyngeal dysphagia who PEG-fed patients compared to NGT-fed patients (adjusted HR: 0.21, 95% CI: 0.10-0.44, p < 0.001). The cumulative incidence of pneumonia requiring hospitalization was significantly lower in the PEG group than in the NGT group (p < 0.001).

Conclusion: mFEES could be a screening tool for oropharyngeal dysphagia. PEG is preferred over NGT for long-term enteral feeding, as it significantly reduces the risk of pneumonia requiring hospitalization, especially in patients with oropharyngeal dysphagia.

Background: Gastro-esophageal reflux disease (GERD) is the most common cause for noncardiac chest pain (NCCP), with an estimated prevalence rate ranging between 30% and 60%. Heartburn and NCCP may share common mechanisms.

Aims/methods: To assess whether particular patterns of impedance-pH variables characterize patients with dominant heartburn, regurgitation, or NCCP and their ability to predict proton pump inhibitor (PPI) response for each symptom, GERD patients, evaluated with high-resolution manometry (HRM) and impedance-pH, were included.

Results: In total, 109 NCCP, 68 heartburn, and 64 regurgitation patients were included. Pathological reflux episodes were observed in 28%, 19%, and 56% (p < 0.001). Pathological mean nocturnal baseline impedance (MNBI) values were observed in 55%, 53%, and 34% (p < 0.05). Hypomotility was more frequent in NCCP compared to heartburn patients (p < 0.05). When comparing NCCP with heartburn, hypomotility was associated with NCCP perception (OR: 2.34, 95% CI: 1.23-4.43; p < 0.01). When comparing NCCP with regurgitation, >80 refluxes and type 2/3 esophagogastric junction (EGJ) were associated with regurgitation perception (OR: 0.31, 95% CI: 0.16-0.59; p < 0.001, and OR: 0.5, 95% CI: 0.27-0.93; p < 0.05), while pathological MNBI was associated with NCCP perception (OR: 2.34, 95% CI: 1.23-4.43; p < 0.01). 45.5% NCCP patients, 45.6% with heartburn, and 36% with regurgitation responded to PPIs (p < 0.05). At multivariate analysis, pathological MNBI or PSPW index were associated with PPI responsiveness in patients with NCCP or heartburn, while in patients with regurgitation, pathological MNBI was associated with PPI responsiveness and a reflux number >80 to PPI refractoriness.

Conclusions: We highlight the usefulness of an accurate clinical and functional evaluation of GERD patients, allowing to discriminate particular characteristics in patients with dominant heartburn, NCCP, or regurgitation, which may benefit of distinct therapeutic strategies.

Background: There is a bidirectional relationship between sleep and pain disturbances. Sleep disturbances increase the risk for chronic pain, while chronic pain can interfere with sleep. Hence, we assessed the subjective sleep characteristics of youth with functional abdominal pain disorders (FAPDs) compared to healthy youth and examined associations with gastrointestinal symptoms.

Methods: We included youth ages 10-18 years without a sleep or organic GI disorder diagnosis from a large private school. Participants completed demographics, sleep history, and validated questionnaires: sleep quality (ASWS-SF), insomnia (PISI), daytime sleepiness (ESS), sleep disturbance (PROMIS SD), sleep-related impairment (PROMIS SRI), and Rome 4 diagnostic questionnaire. Cases (FAPDs) completed abdominal pain index (API), nausea severity (NSS), anxiety, depression (PROMIS), and functional disability (FDI). Parents filled sleep hygiene metrics (SHIP). Cases were matched 1:1 with controls based on age and gender.

Results: Of 120 youth (60 cases and 60 controls), the mean age was 13.5 ± 1.9 years and 50% were females. Youth with FAPDs had higher insomnia, sleep disturbance, sleep-related impairment, daytime sleepiness, sleep hygiene, gasping, and nightmares than healthy youth (p < 0.05). Higher insomnia severity was associated with worse abdominal pain (r = 0.41, p < 0.01), higher daytime sleepiness with a family history of disorders of gut-brain interaction (DGBIs, OR = 14.7, p = 0.002), and higher sleep-related impairment (OR = 5.6, p = 0.02) and depression (OR = 6.1, p = 0.01) with black race.

Conclusion: Youth with FAPDs have worse sleep than healthy youth and multiple sleep parameters are associated with abdominal pain. Future studies could focus on determining mechanisms by which sleep disturbances affect abdominal pain and vice versa.

Background: Evaluate the impact of Spondias mombin L. juice (SM), alone and in combination with Lactobacillus acidophilus, in an experimental model of intestinal mucositis.

Methods: Swiss mice were orally administered with saline, SM, or SM combined with L. acidophilus NRRL B-4495 at 1 × 10⁹ colony-forming unit (CFU/mL) for 15 days before the induction of intestinal mucositis by a single intraperitoneal injection of 5-fluorouracil (5-FU) at 450 mg/kg. On the 18th day, following euthanasia, tissue samples were collected for histopathological examination. Jejunum tissues were analyzed for MUC-2 immunoexpression, concentrations of interleukin-1-beta (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor (TNF)-α, and invertase activity.

Key results: 5-FU induced intestinal damage in all intestinal segments, and this damage involved villus blunting, flattened and vacuolated cells, crypt necrosis, inflammatory cell infiltration, and mucosa and submucosal edema compared to the control group. In contrast, SM or SM with L. acidophilus prevented these morphological alterations in all intestinal segments (p < 0.05). Both treatments reduced the intestinal concentration of IL-1 beta (p < 0.05), IL-6 (p < 0.05), and TNF-alpha (p < 0.05). Notably, the combination of SM and L. acidophilus, but not SM alone, prevented the 5-FU-induced decrease in invertase activity and mucin expression (p < 0.05). Furthermore, SM combined with L. acidophilus resulted in an increased population of lactic acid bacteria in feces on the 7th and 18th days. Combining SM with L. acidophilus also decreased fecal excretion of γ-Ergostenol and γ-sitosterol.

Conclusions and inferences: SM, alone and combined with Lactobacillus acidophilus demonstrated significant protective effects against 5-FU-induced intestinal mucositis, reducing inflammatory markers.

Background: The shear rheology of ingested fluids influences their pharyngo-esophageal transit during deglutition. Thus, swallowed fluids elicit differing physiological responses due to their shear-thinning profile.

Methods: Two hydrocolloid fluids, xanthan gum (XG) and sodium carboxymethylcellulose gum (CMC), were compared in 10 healthy adults (mean age 39 years). Manometry swallowing assessments were performed using an 8-French catheter. Swallows were analyzed using the Swallow Gateway web application (www.swallowgateway.com). Grouped data were analyzed by a mixed statistical model. The coefficient of determination (r²) assessed the relationship between measures and bolus viscosity (SI units, mPa.s) at shear rates of 1-1000 s^-1.

Key results: Rheology confirmed that the thickened fluids had similar viscosities at 50 s^-1 shear rate (XG IDDSI Level-1, 2, and 3 respectively, 74.3, 161.2, and 399.6 mPa.s vs. CMC Level-1, 2, and 3 respectively 78.0, 176.5, and 429.2 mPa.s). However, at 300 s^-1 shear, CMC-thickened fluids exhibited approximately double the viscosity (XG Level-1, 2, and 3 respectively 19.5, 34.4, and 84.8 mPa.s vs. CMC Level-1, 2, and 3 respectively, 41.3, 80.8, and 160.2 mPa.s). In vivo swallows of CMC, when compared to XG, showed evidence of greater flow resistance, such as increased intrabolus pressure (p < 0.01) and UES Integrated Relaxation Pressure (UESIRP, p < 0.01) and shorter UES Relaxation Time (p < 0.05) and Bolus Presence Time (p < 0.001). The apparent fluid viscosity (mPa.s) correlated most significantly with increasing UESIRP (r² 0.69 at 50 s^-1 and r² 0.97 at 300 s^-1, p < 0.05).

Conclusion: Fluids with divergent shear viscosities demonstrated differences in pharyngeal function. These physiological responses were linked to the shear viscosity and not the IDDSI level.

Background: Cyclic vomiting syndrome (CVS) is defined by its episodic patterning. Furthermore, CVS is associated with other episodic disorders such as migraine and epilepsy. Indeed, many of the medications that are known to be useful for prophylaxis and abortive therapy in CVS are also effective in preventing and aborting migraines and seizures. These observations strongly suggest that CVS has a neural basis, but the precise pathophysiological mechanisms that operate in CVS remain unclear.

Purpose: This brief review describes recent neurophysiological insights and opportunities to further advance the understanding of pathophysiological neural mechanisms that are present in patients with CVS. These insights are poised to translate into the next generation of neurotherapeutic strategies for CVS using central neuromodulation. Additionally, the development of neurophysiological tests of neural excitability could be positioned to shape management decisions in future CVS care.

Introduction: Gastrointestinal (GI) magnetic resonance imaging (MRI) enables simultaneous assessment of gastric peristalsis, emptying, and intestinal filling and transit. However, GI MRI in animals typically requires anesthesia, which complicates physiology and confounds interpretation and translation to humans. This study aimed to establish GI MRI in conscious rats, and for the first time, characterize GI motor functions in awake versus anesthetized conditions.

Methods: Fourteen Sprague-Dawley rats were acclimated to remain awake, still, and minimally stressed during MRI. GI MRI was performed under both awake and anesthetized conditions following voluntary consumption of a contrast-enhanced test meal.

Results: Awake rats remained physiologically stable during MRI, giving rise to gastric emptying of 23.7% ± 1.4% at 48 min and robust peristaltic contractions propagating through the antrum at 0.72 ± 0.04 mm/s, with a relative amplitude of 40.7% ± 2.3% and a frequency of 5.1 ± 0.1 cycles per minute. Under anesthesia, gastric emptying was approximately halved, mainly due to a significant reduction in peristaltic contraction amplitude, rather than the change in propagation speed, whereas the contraction frequency remained unchanged. Additionally, the small intestine showed faster filling and stronger motility in awake rats.

Conclusion: This study demonstrates the feasibility of GI MRI in awake rats and highlights notable differences in gastric and intestinal motility between awake and anesthetized states. Our protocol provides a novel and valuable framework for preclinical studies of GI physiology and pathophysiology.

Normal anal sensibility can be present in ARM patients diagnosed with all types of ARM after they have been treated with corrective surgery. Anal sensibility was better in those with a functional IAS. This means that the IAS, present in the distal end of the fistula, should be spared as much as possible to preserve anal sensibility. In this way, aiming to maintain the best possible fecal continence. Furthermore, the outcomes of this study demonstrate that anal sensibility is regulated by transmural nerves.