Hypermobile Ehlers-Danlos Syndrome (hEDS) is a genetic connective tissue disorder characterized by hypermobile joints, chronic pain, fatigue, brain fog, orthostatic intolerance, and GI symptoms and dysmotility. Its heterogeneous presentation contributes to poor quality of life, inappropriate interventions, and prolonged diagnostic delays, often up to 10 years. This study primarily aimed to determine if physiological signals captured by a medical-grade wrist wearable could characterize autonomic patterns in hEDS and relate them to symptoms. Individuals with hEDS (n=30) and healthy controls (n=28) wore a medical grade smartwatch for 30 days, collecting continuous heart rate variability, activity, oxygen saturation, and blood pressure, alongside initial baseline symptom and quality-of-life surveys. Individuals with hEDS showed greater instability and variability in both systolic and diastolic blood pressure as well as the HRV metric LF/HF ratio, in comparison to healthy controls (p-values: 0.04, 0.02, 0.02). During sleep, metrics of parasympathetic activity (HRV measures: HF power, pNN50, RMSSD) trended lower in hEDS than healthy in comparison. As expected, survey domains assessing physiologic symptoms and quality-of-life were significantly worse in the hEDS cohort (p-values < 0.05). Notably, autonomic metrics correlated with GI symptoms in the hEDS cohort (Spearman's ρ range: 0.38-0.60), and psychological symptoms in the healthy cohort (Spearman's ρ range: -0.47-0.41). Principal component analysis (PCA) of physiologic and symptom features clearly separated groups, supporting distinct physiologic profiles. Combination of GI symptom index and wearable monitoring show promise as a hybrid screening approach that could substantially shorten the time to diagnosis in this population.

OBJECTIVE:Prior studies have reported the loss of α-smooth muscle actin (α-SMA) immunoreactivity in the inner circular layer of the muscularis propria in small bowel motility disorder cases, but this remains controversial with conflicting data. In this study, we aimed to characterize α-SMA immunoreactivity in the muscularis propria of the small intestine-specifically, jejunum-in patients with and without small bowel motility disorder. METHODS:A total of 28 transmural proximal jejunum biopsy specimens from adult patients with clinical impression of upper gastrointestinal dysmotility disorder and 64 control tissues were evaluated. The controls were full-thickness, longitudinal tissue sections from segmental resections performed due to gunshot wounds, multivisceral transplant donation, and tumors. Immunostaining for α-SMA was performed with appropriate controls to confirm the presence of immunoreactivity in the circular and longitudinal muscle layers of the muscularis propria in each sample and recorded as retained or diminished. RESULTS:In the small bowel motility disorder and control cases, 42.9% (12/28) and 70.3% (49/64) of the cases showed no or minimal α-SMA immunoreactivity in the inner circular layer with peripheral accentuation, respectively. CONCLUSIONS:Loss or diminished α-SMA immunoreactivity in the inner circular layer of the muscularis propria occurs with a similar frequency in cases with and without small bowel motility disorder and does not correlate with impairment of function.

BACKGROUND & AIMS:Gastric peroral endoscopic myotomy (G-POEM) is an emerging treatment for gastroparesis, but clinical outcomes can be inconsistent; hence, it is vital to enhance our management strategies for patients with clinical failure. METHODS:This was a multicenter retrospective review of patients who underwent G-POEM for refractory gastroparesis from September 2015 to November 2023. Clinical outcomes and management post-G-POEM were assessed and categorized into 4 types based on symptom improvement and gastric emptying metrics. RESULTS:Of the 482 patients, 221 (46%) underwent evaluations with pre- and post-G-POEM gastric emptying tests and were included in the study. Type 1 clinical response (clinical success with improved gastric emptying scintigraphy [GES]) was the most common outcome, occurring in 56%. This was followed by type 4 (clinical failure with no GES improvement) at 23%, type 2 (clinical failure with improved GES) at 15%, and type 3 (clinical success with no GES improvement) at 6.7%. Patients with primary clinical failure (types 2 and 4) showed significantly higher daily opioid use at 23%, compared with 7% in types 1 and 3 (P = .032). Clinical failure overall was observed in 60% during a median follow-up of 48 months, with 31% managed by pylorus-directed retreatment and 7% with gastric neurostimulator placement. In the type 1 response group, clinical success was re-established in 71% following pylorus-directed therapies, with repeat G-POEM being an independent predictor of clinical success post-re-treatment (odds ratio, 2.2; P = .02). CONCLUSIONS:Our study highlights the importance of post-G-POEM GES assessments for characterizing clinical responses. Type 1 responders are more likely to benefit from subsequent pylorus-directed re-treatments, particularly repeat G-POEM interventions. CLINICALTRIALS:gov, Number: NCT04434781.

Background and Aims The postoperative management of gastric peroral endoscopic myotomy (G-POEM) lacks standardization. This study aimed to evaluate adverse events, readmission rates, and feasibility of same-day discharge (SDD) after G-POEM. Methods A multicenter retrospective review of prospectively collected G-POEM data was conducted. The primary outcome was the 15-day readmission rates in SDD and admitted patients. Secondary outcomes included readmission risk factors, clinical success, and adverse events (AEs). Results We found a 4.1% 15-day readmission rate in 482 patients (95% CI, 3.2%-5.4%). SDD clinical success rates at 6 to 12 months were 54.1% versus 59.7% for the admitted group. The overall AE rate was 4.1%. SDD patients tended to have shorter procedure times and higher frequencies of double myotomy and endoscopic suturing for closure. Conclusions G-POEM is safe with low incidence of AEs and 15-day readmission rates. SDD appears safe in uncomplicated cases, suggesting that upper gastrointestinal studies after G-POEM may be unnecessary. ClinicalTrials.gov (NCT04434781).

INTRODUCTION:Studies demonstrate an overlap of constipation with gastroparesis and functional dyspepsia, but the impact of treatments that target constipation on improving upper gastrointestinal (UGI) symptoms is unexplored. We quantified the effects of constipation medication therapies on UGI and constipation symptom severity in subjects presenting with symptoms of gastroparesis. METHODS:Fifty-six subjects with symptoms of gastroparesis underwent concurrent wireless motility capsule and gastric emptying scintigraphy and were recommended to receive either a new medication therapy for constipation or a change in constipation therapy based on investigator interpretation of test results. Gastroparesis Cardinal Symptom Index (GCSI), upper abdominal pain, and constipation scores were compared between baseline and 6 months. Data were compared between delayed or non-delayed gastric emptying and the presence or absence of slow colonic transit. KEY RESULTS:Subjects with slow colonic transit had improvements in GCSI (p = 0.007) and constipation scores (p = 0.004) after treatment with a new or changed constipation medication, with the delayed emptying subgroup driving GCSI improvements (p = 0.004). Reductions in nausea/vomiting (p = 0.02) and early satiety/fullness subscores (p = 0.002) with trends to improved bloating/distention subscores (p = 0.06) were observed in this subgroup, but upper abdominal pain was unchanged. Subjects with normal colonic transit showed no improvement in GCSI scores regardless of gastric emptying status (p > 0.05). CONCLUSIONS AND INFERENCES:Identifying and treating delayed colonic transit in gastroparetic (delayed gastric emptying) subjects improves global UGI symptoms as well as selected individual symptoms. Evaluation of whole gut motility as well as recognizing and managing extragastric delay may promote improved outcomes in these patients. TRIAL REGISTRATION:ClinicalTrials.gov: NCT02022826.

BACKGROUND & AIMS: Prokinetics have limited effectiveness for treating symptoms of gastroparesis. Thus, alternative or adjunct therapies, such as gastroparesis diets or neuromodulators, are often prescribed. Their therapeutic bene fi ts alone or in combination remain unclear. METHODS: One hundred and twenty-nine patients with symptoms of gastroparesis underwent wireless motility capsule gastric emptying time and gastric emptying scintigraphy. Based on test results, changes in therapy were recommended. Changes in Gastroparesis Cardinal Symptom Index (GCSI) and individual symptom scores over 6 months were related to recommendations for prokinetics, gastroparesis diet, or neuromodulators given as solo new therapies or in dual combinations. Multivariate analyses were performed to adjust for gastric emptying and other variables. RESULTS: In the whole group regardless of therapy, GCSI scores decreased by 0.53 points (interquartile range, -1.25 to 0.05; P < .0001) over 6 months. GCSI did not decrease for prokinetics as solo new therapy ( P = .95). Conversely, neuromodulators as solo therapy decreased GCSI scores ( P = .04) and all individual symptoms except nausea/vomiting ( P = .86). Prokinetics combined with gastroparesis diets or neuromodulators improved GCSI scores ( P pound .04) and most individual symptoms. Adjusting for gastric emptying time on multivariate analyses showed greater GCSI decreases for nondelayed emptying for neuromodulators as solo new therapy ( P [ .01). Gastric emptying scintigraphy, gender, diabetes, and functional dyspepsia did not in fl uence responses to any treatment. CONCLUSIONS: Initiating prokinetics as solo new therapy had little bene fi t for patients with symptoms of gastroparesis. Neuromodulators as the only new therapy decreased symptoms other than nausea and vomiting, especially with nondelayed gastric emptying. Adding gastroparesis diets or neuromodulators to prokinetics offered relief, suggesting that combination therapies may be more useful in managing these patients. (ClinicalTrials.gov NCT02022826.)