Neurogastroenterology and Motility最新文献

Objectives: Percutaneous electrical nerve field stimulation (PENFS) is an effective treatment for disorders of gut-brain interaction (DGBI), proposed to influence vagal pathways. Cardiac metrics such as respiratory sinus arrythmia (RSA) and vagal efficiency (VE) can noninvasively assess parasympathetic output. Commonly used antidepressant drugs inhibit vagal signaling and may interfere with PENFS. This study examined immediate effects of active compared to sham PENFS on cardiac vagal function in adolescents with chronic nausea with and without concurrent drug therapy.

Materials and methods: Participants (n = 84) were randomized to active (3.2 V, 1-10 Hz) or sham PENFS within an 8-week prospective, double-blind clinical trial. Subjects underwent posture challenges to elicit a vagal response before and after PENFS device placement mid-way through the study. RSA, mean heart period (HP), and VE were calculated from electrocardiogram recordings. Exposure to antidepressant drugs was recorded.

Results: The mean (SD) age was 15.61 (2.07) years (83% female). Fifty percent were treated with antidepressants. PENFS neurostimulation enhanced VE in patients without antidepressant exposure (mean increase after PENFS stimulation =7.56 [95% CI: 0.26, 14.86], d = 0.30, 17% increase) but not in those treated with antidepressants (mean change = -5.30 [95% CI:-14.28, 3.68]). Sham PENFS did not produce significant VE changes regardless of medication use (both p > 0.40). There were no significant effects on RSA or HP.

Conclusions: Acute enhancement of cardiac VE is demonstrated with PENFS in patients not exposed to chronic antidepressant drug therapy. Findings indicate that VE is a sensitive metric for rapid assessment of PENFS effects but raise concern for possible interaction or interference by standard of care medications.

Trial registration: Clinicaltrials.gov #: 1064187-2.

Background: Cyclic vomiting syndrome (CVS) is a disorder characterized by sudden, recurrent episodes of severe nausea and vomiting. The pathophysiology of CVS is not known but genetic factors that regulate emetic neurocircuitry have been proposed. The aim of this study was to investigate whether different variations in genes encoding serotonin receptors (HTRs) are associated with susceptibility to CVS and/or CVS symptoms.

Methods: This case-control study included 70 patients with CVS:16 male and 54 female, and 2504 healthy controls from the 1000 Genomes Project database. Single-nucleotide polymorphisms (SNPs) in genes encoding serotonin receptors (HTR1B, HTR1D, HTR3B and HTR3C) and correlations between SNPs and the symptoms of CVS were determined.

Key results: Our study discovered that patients with GG, AA and GG genotypes of HTR1B/D rs6296, rs6298 and rs6300, respectively, as well as the CC genotype of HTR3B rs176744 are associated with an increased risk (p < 0.001), whereas allele C in rs3788987 (HTR3B, p < 0.01) and allele A in rs6766410 (HTR3C, p < 0.05) were associated with a decreased risk of CVS. In addition, statistical analysis indicated that CVS patients with GA or AA genotypes of HTR1D rs676643 gene have a seven-fold increase in risk of depression compared to patients with GG genotype (p < 0.01).

Conclusions and inferences: Our study revealed for the first time that variations in 5-HTR genes may contribute to CVS susceptibility and CVS-related symptoms.

Background: The carbon-13 spirulina gastric emptying breath test (GEBT) is approved to identify delayed, but not accelerated, gastric emptying (GE). We compared the utility of the GEBT to scintigraphy for diagnosing abnormal GE in patients with diabetes mellitus.

Methods: Twenty-eight patients with diabetes ate a 230-kcal test meal labeled with technetium 99 m and ¹³C-spirulina, after which 10 scintigraphic images and breath samples (baseline, 15, 30, 45, 60, 90, 120, 150, 180, 210, and 240 min) were collected on 2 occasions 1 week apart. We assessed the accuracy of ¹³C-spirulina GEBT excretion rate (percent dose multiplied by 1000 [kPCD] min^-1) values to predict scintigraphic half-life and distinguish between normal, delayed, and accelerated GE and the intraindividual reproducibility of the GEBT.

Key results: Scintigraphy revealed normal, delayed, and accelerated GE, respectively, in 17 (30%), 29 (52%), and 10 (18%) test results. GE T½ values measured with scintigraphy and GEBT were highly concordant within individuals; the intraindividual reproducibility was 34% (scintigraphy) and 15% (GEBT). Compared to current criteria, the kPCD150 (150 min) and kPCD180 values provided equally sensitive (90%) and more specific (81% vs. 67%) approach for distinguishing between delayed versus normal/accelerated GE. A new metric (kPCD60-kPCD15 min) was 90% sensitive and 83% specific for distinguishing between accelerated versus normal/delayed GE. These findings were used to create nomograms and an algorithm for interpreting GEBT results.

Conclusions and inferences: Among patients with poorly controlled diabetes, the ¹³C-spirulina GEBT can accurately and precisely assess GE and effectively distinguish between normal, delayed, and accelerated GE.

The role of esophageal motility in determining GERD severity has been widely explored. Kamboj et al. show that IEM diagnosis is associated with increased GERD severity. We aim to further highlight the impact of IEM in reflux burden, as demonstrated by several recent studies in patients with both typical and atypical symptoms.

Background: Transanal irrigation is a well-established minimally invasive therapy that addresses symptoms of both constipation and incontinence. The therapy has been extended from just neurogenic bowel dysfunction patients to those with disorders of brain-gut interaction and postsurgical conditions.

Aim: To summarized the literature on transanal irrigation and update the contraindication profile.

Materials and methods: We undertook a literature review of transanal irrigation complications and outcomes.

Results: Initiation of therapy as part of a bowel care regime is becoming more common outside specialist centers. In addition, the concept of both high- and low-volume irrigation schedules has entered the treatment paradigm, and it is clear that there is a differing safety profile. We present an update from the previous long list of contraindications.

Discussion: We describe how optimizing long-term adherence depends on these factors in addition to a structured follow-up programme.

Conclusion: Transanal irrigation is an increasingly used therapy, with a good safety profile, further improved by the advent of low-volume irrigation options. Key to safe and effective usage of transanal irrigation is careful patient selection allied to tailored initial training of the patient.

Background: Proton pump inhibitors (PPI) for gastroesophageal reflux disease (GERD) are associated with a high failure rate. Our uncontrolled feasibility study aimed determining the effect of a transcutaneous electrical stimulation system (TESS) on GERD symptoms and acid exposure time (AET).

Methods: Recruited patients with heartburn and regurgitation. During the first phase (one-week, run-in period, off-PPI's), patients completed symptom diaries and demographic questionnaires. Thereafter, all patients underwent gastroscopy with subsequent placement of a wireless esophageal pH capsule, off-PPI. Based on pH analysis in the first 24 h, only those with increased AET (percent total time pH < 4 above 6%) continued to the next phase. During that phase, patients were treated for up to 3 weeks with TESS and documented their symptoms. The Primary endpoint was the magnitude of reduction in GERD-related symptoms. The secondary endpoints were the magnitude of reduction of AET and DeMeester score, as compared with their baseline values.

Results: Included 31 patients and of those, 26 patients (42% females, aged 49 ± 15 years, mean BMI 25 ± 3 kg/m²) completed the first two phases of the study. At baseline, mean number of daily heartburn and regurgitation episodes was 2.55 ± 1.79 and 1.40 ± 1.73, respectively. Following TESS, mean number of daily heartburn and regurgitation episodes dropped to 0.77 ± 0.75 and 0.36 ± 0.8, respectively (p < 0.001). At base line, mean AET and DeMeester score were 12.4 ± 5.6 and 32.1 ± 12.7, respectively. Following TESS mean AET dropped to 6.0 ± 3.5 and DeMeester score dropped to 16.2 ± 8.2 (p < 0.001).

Conclusions: TESS is effective in reducing both symptoms and esophageal AET in GERD patients.

Introduction: Fluid thickeners used in the management of oropharyngeal dysphagia exhibit non-Newtonian shear-thinning rheology, impacting their viscosity during deglutition. This study investigated how the rheological properties of thickened fluids affect pharyngeal swallowing parameters in patients with oropharyngeal motor disorders diagnosed by pharyngeal high-resolution manometry impedance (P-HRM-I).

Methods: Seventy-two patients (18-89 years) referred for P-HRM-I were diagnostically assessed with a 10 mL thin bolus. In 57 of the patients, 10 mL swallows of two moderately thick formulations-xanthan gum (XG) and sodium carboxymethylcellulose gum (CMC)-were also tested. The XG and CMC fluids had equivalent empirical thickness but different viscosity at pharyngeal phase shear rates: XG 87 mPa.s (83-91) versus CMC mean 157 mPa.s (148-164) at 300 s^-1. Standard metrics of pharyngeal and upper esophageal sphincter (UES) function were derived from P-HRM-I recordings and analyzed to characterize patients into one of four disorder subtypes: (i) No Disorder, (ii) UES Disorder, (iii) Pharyngeal Disorder, and (iv) Combination UES/Pharyngeal Disorder. Impedance recordings also assessed pharyngeal bolus transit.

Results: Patients with a Combination UES/Pharyngeal Disorder were most likely to have abnormal bolus transit (82%, p < 0.001). Increasing bolus viscosity significantly influenced UES residual pressure, UES opening area, and post-swallow residue. Patients with UES Disorder exhibited pronounced increases in UES residual pressure with CMC compared to XG. Pharyngeal contractility was unaffected by viscosity changes. Post-swallow residue increased with CMC, particularly in patients with a Combination Disorder. Case-by-case analysis revealed individual variability in response to the different viscosities.

Conclusion: The rheological properties of thickened fluids significantly affect swallowing function, with these effects dependent upon the disorder subtype.

Background: Gastric accommodation (GA) testing is gaining clinical recognition as novel and minimally invasive modalities emerge. We investigated the feasibility of hybrid nuclear imaging volumetry (SPECT/CT) and combined high-resolution manometry-nutrient drink test (HRM-NDT) to assess GA.

Methods: In this non-randomized pilot study, [^99mTc]NaTcO₄ gastric SPECT/CT (250 mL protocol) and proximal gastric HRM-NDT (~60 mL/min protocol) were performed separately within 30 days using Ensure Gold test meal (1.05 kcal/mL; Abbott). GA parameters were measured, and their preliminary associations were examined using Spearman's ρ and Hoeffding's D correlation tests. Data were presented as median ± normalized median absolute deviation.

Key results: Twenty healthy, asymptomatic individuals (11 females; 23.5 ± 2.2 years, 23.7 ± 2.2 kg/m²) completed both procedures without serious adverse events and interrupted sessions. The accommodation volume and postprandial-to-fasting volume ratio from SPECT/CT were 325.8 ± 28.5 mL and 5.31 ± 1.28, respectively. During HRM-NDT, the nadir-intragastric pressure (IGP) was -6.6 ± 3.6 mmHg at an ingested volume of 360.0 ± 177.9 mL, and the area-under-curve of IGP was -1566.0 ± 1596.8 mmHg·mL. The maximum tolerated volume for reaching satiety/maximum discomfort was 450.0 ± 177.9 mL, and the area-under-curve of satiation score was 900.0 ± 266.9 satiation-unit·mL. The area-under-curve of IGP showed significant associations with maximum tolerated volume (ρ: -0.702; D: 0.234) and the area-under-curve of satiation score (D: 0.119): all p < 0.01. No correlations were found between volumetric with manometric and subjective NDT GA parameters.

Conclusions & inferences: SPECT/CT and HRM-NDT are feasible and tolerable techniques for measuring GA in healthy individuals. Thus, determining their diagnostic utility among patient populations requires further optimization and standardization.

Background: Constipation is one of the most common non-motor symptoms in patients with Parkinson's disease (PD), which could manifest during the early stage of the disease. However, the etiology of constipation in PD remains largely unknown. Previous studies supported that gastrointestinal dysfunction may be associated with functional connectivity alterations in paraventricular hypothalamic nucleus (PVN). Therefore, this study aimed to investigate the potential contribution of the PVN to the pathogenesis of constipation in a cohort of early-stage patients with PD and to compare brain network organization between PD patients with and without constipation.

Methods: A total of 66 PD patients (PD with constipation and without constipation) and 30 healthy controls were prospectively enrolled. All participants acquired T1-weighted and resting-state fMRI scans. Then we employed voxel-based morphometry analysis and functional connectivity analysis.

Results: We observed a decreased functional connectivity in the PVN-pontine tegmentum pathway in PD patients with constipation compared to the patients without constipation (p = 0.006, t = 5.37), while we did not find any changes in basal ganglia circuitry between these two groups. In addition, we found that the functional connectivity between PVN and pontine tegmentum was negatively associated with the UPDRS I, II, III and NMSS scores (p < 0.05). Meanwhile, these two types of patients also showed substantial differences in functional connections linking the inferior frontal gyrus and cerebellum with multiple brain regions. We discovered no statistical difference in gray matter volume among these two groups.

Conclusions: Our study provides further insights into the dysfunctional mechanisms of constipation, suggesting that abnormal PVN functional connectivity may be related to the mechanism of constipation in PD. Meanwhile, the inferior frontal gyrus and cerebellum may be involved in the occurrence of constipation in PD patients.

Background: Refluxate volume and pH drop following gastroesophageal reflux are mostly cleared by peristalsis. We evaluated the roles of primary volume clearing peristaltic wave (VCPW), secondary VCPW, post-reflux swallow-induced peristaltic wave (PSPW), and late primary peristaltic wave (LPPW) in refluxate clearance.

Methods: We retrospectively analyzed pH-impedance studies performed off therapy in 40 patients with typical esophageal symptoms. Mechanism of refluxate clearance was evaluated for each reflux episode (primary VCPW vs. secondary VCPW vs. none), as well as presence of PSPW, LPPW when PSPW was absent, and pH recovery with each mechanism. Per-episode and per-patient analyses determined the dominant mechanism of refluxate clearance and pH recovery.

Results: Of 958 reflux episodes, 88% were acidic. A primary VCPW was the dominant mechanism for volume clearance (48.4% acid, 47.8% non-acid reflux episodes), and ≥ 50% pH recovery (58.7%). Of reflux episodes lacking pH recovery, PSPW resulted in ≥ 50% pH recovery in 40.2%, and LPPW in 60.9%. In logistic regression models, primary peristaltic wave (primary VCPW, PSPW, or LPPW) had the highest likelihood of pH recovery in per-episode analysis (OR 2.1, CI 1.3-3.0, p < 0.001), and in per-patient analysis (OR 11.0, CI 1.5-20.5, p = 0.025), among which primary VCPW was the most effective (OR 3.4, CI 1.5-7.7, p = 0.003).

Conclusions: A primary peristaltic wave from a swallow, either in the form of a VCPW, PSPW, or LPPW, is the dominant mechanism of pH recovery after gastroesophageal reflux. When a primary VCPW does not correct pH drop, PSPW, and LPPW are equivalent salvage mechanisms for pH recovery.