Low Vitamin D Levels in Patients with Symptoms of Gastroparesis: Relationships with Nausea and Vomiting, Gastric Emptying and Gastric Myoelectrical Activity.

Patients with gastroparesis (Gp) often have diets deficient in calories, electrolytes, and vitamins. Vitamin D levels have been reported to be low in some patients with Gp but has not been systematically studied. AIMS: To determine vitamin D levels and relationships among symptoms, gastric emptying and gastric myoelectrical activity (GMA) in patients with symptoms of Gp. METHODS: 25-hydroxy-vitamin D was measured in patients at enrollment in the Gastroparesis Clinical Consortium Registry. Gastroparesis Cardinal Symptoms Index (GCSI), gastric emptying, and GMA before and after water load satiety test (WLST) were measured. GMA, expressed as percentage distribution of activity in normal and dysrhythmic ranges, was recorded using electrogastrography. RESULTS: Overall, vitamin D levels were low (< 30 ng/ml) in 288 of 513 (56.1%) patients with symptoms of Gp (206 of 376 (54.8%) patients with delayed gastric emptying (Gp) and 82 of 137 (59.9%) patients with symptoms of Gp and normal gastric emptying). Low vitamin D levels were associated with increased nausea and vomiting (P < 0.0001), but not with fullness or bloating subscores. Low vitamin D levels in patients with Gp were associated with greater meal retention at four hours (36% retention) compared with Gp patients with normal vitamin D levels (31% retention; P = 0.05). Low vitamin D in patients with normal gastric emptying was associated with decreased normal 3 cpm GMA before (P = 0.001) and increased tachygastria after WLST (P = 0.01). CONCLUSIONS: Low vitamin D levels are present in half the patients with symptoms of gastroparesis and are associated with nausea and vomiting and gastric neuromuscular dysfunction.

Large-Caliber Empiric Esophageal Dilation Results in Sustained Improvement for Selected Patients With Nonobstructive Dysphagia.

INTRODUCTION: Empiric esophageal dilation (EED) remains a controversial practice for managing nonobstructive dysphagia (NOD) secondary to concerns about safety and efficacy. We examine symptom response, presence of tissue disruption, and adverse events (AEs) after EED. METHODS: We examined large-caliber bougie EED for NOD at 2 tertiary referral centers: retrospectively evaluating for AEs. Esophageal manometry diagnoses were also reviewed. We then prospectively assessed EED's efficacy using the NIH Patient-Reported Outcomes Measurement Information System disrupted swallowing questionnaire to assess dysphagia at baseline, 1, 3, and 6 months after EED. Treatment success was defined by improvement in patient-reported outcome scores. RESULTS: AE rate for large-caliber dilation in the retrospective cohort of 180 patients undergoing EED for NOD was low (0.5% perforations, managed conservatively). Visible tissue disruption occurred in 18% of patients, with 47% occurring in the proximal esophagus. Obstructive motility disorders were found more frequently in patients with tissue disruption compared with those without (44% vs 14%, P = 0.05). The primary outcome, the mean disrupted swallowing T -score was 60.1 ± 9.1 at baseline, 56.1 ± 9.5 at 1 month ( P = 0.03), 57 ± 9.6 at 3 months ( P = 0.10), and 56 ± 10 at 6 months ( P = 0.02) (higher scores note more symptoms). EED resulted in a significant and durable improvement in dysphagia and specifically solid food dysphagia among patients with tissue disruption. DISCUSSION: EED is safe in solid food NOD and particularly effective when tissue disruption occurs. EED tissue disruption in NOD does not preclude esophageal dysmotility.

Association of glucagon-like peptide receptor 1 agonist therapy with the presence of gastric contents in fasting patients undergoing endoscopy under anesthesia care: a historical cohort study.

PURPOSE: We aimed to estimate the association of glucagon-like peptide 1 (GLP-1) receptor agonist therapy with the incidence of endoscopically visible gastric contents after preprocedural fasting. METHODS: We reviewed the records of esophagogastroduodenoscopy (EGD) performed at our institution between 2019 and 2023 and determined the presence of residual gastric contents from the procedure notes and saved images. We compared patients taking GLP-1 agonists at the time of the procedure (GLP group, 90 procedures) with patients who started GLP-1 agonist therapy within 1,000 days after undergoing EGD (control, 102 procedures). We excluded emergent procedures without fasting, combined EGD/colonoscopy procedures, and patients with known gastroparesis or previous gastric surgery. We estimated the association between GLP-1 agonist therapy and residual gastric contents with a confounder-adjusted generalized linear mixed effect model. RESULTS: Compared with controls, the GLP cohort had a higher age, American Society of Anesthesiologists' Physical Status, and incidence of nausea and diabetes mellitus. Body mass index and fasting duration were comparable between groups. Visible gastric content was documented in 17 procedures in the GLP group (19%) and in five procedures in the control group (5%), with an associated confounder adjusted odds ratio of 5.8 (95% confidence interval, 1.7 to 19.3; P = 0.004). There were five instances of emergent endotracheal intubation in the GLP group vs one case in control and one case of pulmonary aspiration vs none in control. CONCLUSIONS: In fasting patients, GLP-1 agonist therapy was associated with an increased incidence of residual gastric contents, potentially posing an additional risk of periprocedural pulmonary aspiration.

RéSUMé: OBJECTIF: Notre objectif était d'estimer l'association d'un traitement par agonistes des récepteurs du peptide-1 de type glucagon (glucagon-like peptide 1, GLP-1) avec l'incidence de contenu gastrique visible par endoscopie malgré le jeûne préopératoire. MéTHODE: Nous avons examiné les dossiers des œsophagogastroduodénoscopies (OGD) réalisées dans notre établissement entre 2019 et 2023 et déterminé la présence de contenu gastrique résiduel à partir des notes d'intervention et des images enregistrées. Nous avons comparé les patient·es prenant des agonistes du GLP-1 au moment de l'intervention (groupe GLP, 90 procédures) avec les patient·es qui ont commencé un traitement par agonistes du GLP-1 dans les 1000 jours suivant l'OGD (groupe témoin, 102 procédures). Nous avons exclu les procédures d'urgence sans jeûne, les procédures combinées OGD/coloscopie et les patient·es présentant une gastroparésie connue ou une chirurgie gastrique antérieure. Nous avons estimé l'association entre le traitement par agonistes du récepteur GLP-1 et le contenu gastrique résiduel à l'aide d'un modèle linéaire généralisé à effets mixtes ajusté en fonction des facteurs de confusion. RéSULTATS: Par rapport aux témoins, la cohorte GLP était plus âgée, de statut physique selon l'American Society of Anesthesiologists plus élevé et présentait une incidence plus élevée de nausées et de diabète. L'indice de masse corporelle et la durée du jeûne étaient comparables entre les groupes. Du contenu gastrique visible a été documenté dans 17 procédures dans le groupe GLP (19 %) et dans cinq procédures dans le groupe témoin (5 %), avec un rapport de cotes ajusté associé de 5,8 (intervalle de confiance à 95 %, 1,7 à 19,3; P = 0,004). Il y a eu cinq cas d'intubation endotrachéale urgente dans le groupe GLP vs un cas dans le groupe témoin et un cas d'aspiration pulmonaire vs aucun dans le groupe témoin. CONCLUSION: Chez la patientèle à jeun, le traitement par agonistes des récepteurs du GLP-1 a été associé à une incidence accrue de contenu gastrique résiduel, ce qui pourrait entraîner un risque supplémentaire d'aspiration pulmonaire périprocédurale.

Single cell atlas of human gastric muscle immune cells and macrophage-driven changes in idiopathic gastroparesis.

Gastrointestinal immune cells, particularly muscularis macrophages (MM) interact with the enteric nervous system and influence gastrointestinal motility. Here we determine the human gastric muscle immunome and its changes in patients with idiopathic gastroparesis (IG). Single cell sequencing was performed on 26,000 CD45+ cells obtained from the gastric tissue of 20 subjects. We demonstrate 11 immune cell clusters with T cells being most abundant followed by myeloid cells. The proportions of cells belonging to the 11 clusters were similar between IG and controls. However, 9/11 clusters showed 578-11,429 differentially expressed genes. In IG, MM had decreased expression of tissue-protective and microglial genes and increased the expression of monocyte trafficking and stromal activating genes. Furthermore, in IG, IL12 mediated JAK-STAT signaling involved in the activation of tissue-resident macrophages and Eph-ephrin signaling involved in monocyte chemotaxis were upregulated. Patients with IG had a greater abundance of monocyte-like cells. These data further link immune dysregulation to the pathophysiology of gastroparesis.

Management of Gastrointestinal Symptoms in Parkinson's Disease: A Comprehensive Review of Clinical Presentation, Workup, and Treatment.

Gastrointestinal symptoms in Parkinson's disease (PD) are among the most prevalent and debilitating of complications and present unique diagnostic and management challenges. Patients with PD commonly experience dysphagia, nausea, bloating, and constipation related to pathologic involvement of the enteric nervous system. In turn, gastrointestinal complications may impact motor fluctuations and the efficacy of levodopa therapy. This review will explore the common gastrointestinal manifestations of PD with an emphasis on clinical presentation, workup, and treatment strategies.

Influence of patient-clinician relationship style on acupuncture outcomes in functional dyspepsia: A multi-site randomized controlled trial in Korea.

INTRODUCTION: Research suggests that a warm and empathic "patient-centered" patient-clinician relationship produces better clinical outcomes when compared with a more neutral "disease-centered" relationship. Acupuncturists performed both styles of therapy for patients with functional dyspepsia in Korea. METHODS: The present randomized controlled trial assigned patients (n = 73) to identical acupuncture treatment with either patient-centered augmented care or disease-centered limited care. The Korean version of the Nepean Dyspepsia Index (NDI-K) was the primary outcome measure. Secondary outcome measures included Consultation And Relational Empathy (CARE) scale. RESULTS: Both groups showed improvement in NDI-K. Patient-centered augmented acupuncture produced less effective symptom improvement compared to disease-centered limited acupuncture (NDI-K sum score and frequency; P = 0.008 and P = 0.037 respectively). CARE scores were higher for the augmented versus limited group (P = 0.001), supporting the fidelity of the experimentally controlled patient/clinician relationship. There were no significant differences between the groups in any of other secondary outcomes. CONCLUSION: Patients demonstrated greater improvement following acupuncture conducted with a more neutral, "disease-centered" style of relationship. This result is counter to similar research conducted in Western countries and suggests that cultural factors can significantly shape optimum styles of acupuncture therapy. PRACTICE IMPLICATIONS: Clinicians should consider cultural differences when applying acupuncture therapy.

Benefits of Prokinetics, Gastroparesis Diet, or Neuromodulators Alone or in Combination for Symptoms of Gastroparesis.

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 benefits 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 ≤ .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 influence responses to any treatment. CONCLUSIONS: Initiating prokinetics as solo new therapy had little benefit 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.).

Safety of Pneumatic Dilation in Older Adults with Achalasia: An International Multicenter Cross-Sectional Study.

BACKGROUND: Pneumatic dilation (PD) is an effective first line treatment option for many patients with achalasia. PD use may be limited in adults with achalasia who are older than 65 because of concern for adverse events (AE), and less efficacious therapies are often utilized. We explored the periprocedural safety profile of PD in older adults. METHODS: An international real world cross-sectional study of patients undergoing PD between 2006-2020 in two tertiary centers. Thirty-day AEs were compared between older adults (65 and older) with achalasia and younger patients. RESULTS: A total of 252 patients underwent 319 PDs. In 319 PDs, 18 (5.7%) complications occurred: 6 (1.9%) perforations and 12 (3.8%) emergency department referrals with benign (non-perforation) chest pain, of which 9 (2.8%) were hospitalized. No bleeding or death occurred within 30 days. Perforation rates were similar in both age groups and across achalasia subtypes. Advanced age was protective of benign chest pain complications in univariate analysis, and the limited number of AEs precluded multivariable analysis. CONCLUSIONS: The safety of PD in older adults is at least comparable to that of younger patients and should be offered as an option for definitive therapy for older patients with achalasia. Our results may affect informed consent discussions.

A pilot genome-wide association study meta-analysis of gastroparesis.

BACKGROUND: Gastroparesis (GP) is characterized by delayed gastric emptying in the absence of mechanical obstruction. OBJECTIVE: Genetic predisposition may play a role; however, investigation at the genome-wide level has not been performed. METHODS: We carried out a genome-wide association study (GWAS) meta-analysis on (i) 478 GP patients from the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium (GpCRC) compared to 9931 population-based controls from the University of Michigan Health and Retirement Study; and (ii) 402 GP cases compared to 48,340 non-gastroparesis controls from the Michigan Genomics Initiative. Associations for 5,811,784 high-quality SNPs were tested on a total of 880 GP patients and 58,271 controls, using logistic mixed models adjusted for age, sex, and principal components. Gene mapping was obtained based on genomic position and expression quantitative trait loci, and a gene-set network enrichment analysis was performed. Genetic associations with clinical data were tested in GpCRC patients. Protein expression of selected candidate genes was determined in full thickness gastric biopsies from GpCRC patients and controls. RESULTS: While no SNP associations were detected at strict significance (p ≤ 5 × 10-8 ), nine independent genomic loci were associated at suggestive significance (p ≤ 1 × 10-5 ), with the strongest signal (rs9273363, odds ratio = 1.4, p = 1 × 10-7 ) mapped to the human leukocyte antigen region. Computational annotation of suggestive risk loci identified 14 protein-coding candidate genes. Gene-set network enrichment analysis revealed pathways potentially involved in immune and motor dysregulation (pFDR ≤ 0.05). The GP risk allele rs6984536A (Peroxidasin-Like; PXDNL) was associated with increased abdominal pain severity scores (Beta = 0.13, p = 0.03). Gastric muscularis expression of PXDNL also positively correlated with abdominal pain in GP patients (r = 0.8, p = 0.02). Dickkopf WNT Signaling Pathway Inhibitor 1 showed decreased expression in diabetic GP patients (p = 0.005 vs. controls). CONCLUSION: We report preliminary GWAS findings for GP, which highlight candidate genes and pathways related to immune and sensory-motor dysregulation. Larger studies are needed to validate and expand these findings in independent datasets.

Impact of outpatient gastroenterology consult on pharmacotherapy and management of gastrointestinal symptoms in Parkinson's Disease.

Background & aims: Gastrointestinal (GI) symptoms are common in Parkinson's Disease (PD) patients, and GI dysmotility is thought to induce motor fluctuations, requiring escalation of levodopa therapy. The role of GI consultation in managing such symptoms, however, is unclear. In this study, we investigate the possible association between GI dysmotility symptoms and escalated LEDD therapy, as well as factors associated with GI consultation for PD symptom management. Methods: This was a retrospective case-study of 248 PD patients evaluated by outpatient neurology at Massachusetts General Brigham Healthcare from 2018 to 2022. Logistic regression, t-test, and Fisher exact tests were performed to identify factors associated with GI consult, change in LEDD with consult, and association of consultation with GI diagnoses and treatments, respectively. Results: Among 248 PD patients, 12.9% received GI consultation despite 96.8% having GI symptoms. Bloating was the primary symptom associated with receiving GI consultation (OR 3.59 [95% CI 1.47-8.88], p = 0.005). GI consultation increased the odds of receiving GI-specific medications (78.2% vs 46.3%, p = 0.001) and specialized GI diagnoses like gastroparesis (9.4% vs 0.46%, p < 0.001) and pelvic floor dysfunction (15.6% vs 0%, p < 0.0001). Interestingly, LEDD tended not to change after GI consultation, and dysmotility symptoms, including bloating, did not predict need for higher LEDD. Conclusions: While treating symptoms of dysmotility may not ameliorate levodopa-based motor fluctuations as much as previously thought, GI consultations are underutilized in PD, and patients who receive GI consultation are more likely to have changes in GI diagnosis and treatment.

Antibiotic use as a risk factor for irritable bowel syndrome: Results from a nationwide, case-control study.

BACKGROUND: The microbiome plays an important role in the pathophysiology of irritable bowel syndrome (IBS). Antibiotic use can fundamentally alter gut microbial ecology. We examined the association of antibiotic use with IBS in a large population-based investigation. METHODS: A case-control study with prospectively collected data on 29,111 adult patients diagnosed with IBS in Sweden between 2007 and 2016 matched with 135,172 controls. Using a comprehensive histopathology cohort, the Swedish Patient Register, and the Prescribed Drug Register, we identified all consecutive cases of IBS in addition to cumulative antibiotic dispensations accrued until 1 year prior to IBS (exclusionary period) for cases and time of matching for up to five general population controls matched on the basis of age, sex, country and calendar year. Conditional logistic regression estimated multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of IBS. RESULTS: Patients with IBS (n = 29,111) were more likely than controls (n = 135,172) to have used antibiotics up to 1 year prior to diagnosis (74.9% vs. 57.8%). After multivariable adjustment, this translated to a more than twofold increased odds of IBS (OR 2.21, 95% CI 2.14-2.28) that did not differ according to age, sex, year of IBS diagnosis or IBS subtype. Compared to none, 1-2 (OR 1.67, 95% CI 1.61-1.73) and ≥3 antibiotics dispensations (OR 3.36, 95% CI 3.24-3.49) were associated with increased odds of IBS (p for trend <0.001) regardless of the antibiotic class. CONCLUSIONS: Prior antibiotics use was associated with an increased odds of IBS with the highest risk among people with multiple antibiotics dispensations.

Brief cognitive-behavioral treatment for avoidant/restrictive food intake disorder in the context of functional dyspepsia: Study protocol for a feasibility randomized controlled trial.

BACKGROUND: Avoidant/restrictive food intake disorder (ARFID) symptoms are common (up to 40%) among adults with functional dyspepsia (FD), a disorder of gut-brain interaction characterized by early satiation, post-prandial fullness, epigastric pain, and/or epigastric burning. Using an 8-session exposure-based cognitive-behavioral treatment (CBT) for adults with FD + ARFID compared to usual care (UC) alone, we aim to: (1) determine feasibility, (2) evaluate change in clinical outcomes in, and (3) explore possible mechanisms of action. METHODS: We will randomize adults with FD who meet criteria for ARFID with ≥5% weight loss (N = 50) in a 1:1 ratio to CBT (with continued UC) or to UC alone. A priori primary benchmarks will be: ≥75% eligible participants enroll; ≥75% participants complete assessments; ≥70% participants attend 6/8 sessions; ≥70% of sessions have all content delivered; ≥70% participants rate Client Satisfaction Questionnaire scores above scale midpoint. We will also examine the size of changes in FD symptom severity and related quality of life within and between groups, and explore possible mechanisms of action. CONCLUSIONS: Findings from this trial will inform next steps with treatment development or evaluation-either for further refinement or for next-step efficacy testing with a fully-powered clinical trial.

Randomized clinical trial: A phase 2b controlled study of the efficacy and safety of trazpiroben (TAK-906) for idiopathic or diabetic gastroparesis.

BACKGROUND: Previous clinical studies of trazpiroben, a dopamine D2 /D3 receptor antagonist for long-term treatment of moderate-to-severe idiopathic and diabetic gastroparesis, have shown improved symptoms of fullness. This study assessed trazpiroben efficacy, safety, and tolerability in adults with idiopathic and diabetic gastroparesis versus placebo. METHODS: This global, multicenter, double-blind, parallel-group, phase 2b study (NCT03544229) enrolled eligible adults aged 18-85 years with symptomatic idiopathic or diabetic gastroparesis. Randomized participants received either oral placebo or trazpiroben 5, 25, or 50 mg, administered twice daily over 12 weeks, and completed the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index-Daily Diary. Change in weekly composite score from baseline to week 12 (primary endpoint) and treatment-emergent adverse events were assessed. Data were summarized descriptively. KEY RESULTS: Overall, 242 participants were enrolled (mean [standard deviation] age 55.7 [14.2] years; 75.6% female); 193 completed the study. No significant differences in change from baseline in weekly average of the daily diary composite score occurred at week 12 between placebo (least-squares mean [standard error] -1.19 [0.12]) and trazpiroben (5, 25, and 50 mg: -1.11 [0.22], -1.17 [0.12], and -1.21 [0.12], respectively). Overall, 41.4% of participants receiving trazpiroben reported treatment-emergent adverse events (placebo, 39.7%). No serious events were considered trazpiroben-related; no life-threatening or fatal events were reported. CONCLUSIONS & INFERENCES: There was no clinically meaningful difference in efficacy between trazpiroben and placebo in treating gastroparesis, based on the primary endpoint analysis. Trazpiroben was well tolerated with no new safety concerns identified, strengthening evidence supporting its favorable safety profile. NCT number: NCT03544229.

Relationships among intragastric meal distribution during gastric emptying scintigraphy, water consumption during water load satiety testing, and symptoms of gastroparesis.

Gastric emptying scintigraphy (GES) measures total gastric retention after a solid meal and can assess intragastric meal distribution (IMD). Water load satiety test (WLST) measures gastric capacity. Both IMD immediately after meal ingestion [ratio of proximal gastric counts after meal ingestion to total gastric counts at time 0 (IMD0)] and WLST (volume of water ingested over 5 min) are indirect measures of gastric accommodation. In this study, IMD0 and WLST were compared with each other and to symptoms of gastroparesis to gauge their clinical utility for assessing patients with symptoms of gastroparesis. Patients with symptoms of gastroparesis underwent GES to obtain gastric retention and IMD0, WLST, and filled out patient assessment of upper GI symptoms. A total of 234 patients with symptoms of gastroparesis were assessed (86 patients with diabetes, 130 idiopathic, 18 postfundoplication) and 175 (75%) delayed gastric emptying. Low IMD0 <0.568 suggesting initial rapid transit to the distal stomach was present in 8% and correlated with lower gastric retention, less heartburn, and lower volumes consumed during WLST. Low WLST volume (<238 mL) was present in 20% and associated with increased severity of early satiety, postprandial fullness, loss of appetite, and nausea. Low IMD0 is associated with less gastric retention and less heartburn. Volume of water consumed during WLST, while associated with IMD0, has associations with early satiety, postprandial fullness, loss of appetite, and nausea. Thus, IMD0 and WLST appear to overlap somewhat in their assessment of gastric physiology in adults with symptoms of gastroparesis but relate to different dyspeptic symptoms.NEW & NOTEWORTHY IMD0 and WLST were assessed for their clinical utility in assessing patients with symptoms of gastroparesis. Low IMD0 is associated with less gastric retention and less heartburn. Volume of water consumed during WLST, while associated with IMD0, has associations with early satiety, postprandial fullness, loss of appetite, and nausea. IMD0 and WLST appear to overlap somewhat in their assessment of gastric physiology in adults with symptoms of gastroparesis but relate to different dyspeptic symptoms.

Gastrointestinal Sensory Neuropathy and Dysmotility in Fabry Disease: Presentations and Effect on Patient's Quality of Life.

INTRODUCTION: Fabry disease is a rare multisystemic lysosomal disease resulting in variable manifestations of the gastrointestinal (GI), neurologic, cardiac, and renal systems. Whether GI manifestations are a result of gut dysmotility is undetermined. We aimed to explore GI manifestations in depth and their effect on patients with Fabry disease and to characterize gut motility. METHODS: We recruited adult patients with Fabry disease reporting GI manifestations. All patients answered a battery of questionnaires covering symptom severity, GI-specific quality of life, and effects of work/productivity and underwent a wireless motility capsule test to measure pan-gut motility. RESULTS: In 48 patients with Fabry disease, abnormal bowel habits and abdominal pain were the most common symptoms. Bloating, nausea, vomiting, and reflux were also prevalent. Neurologic manifestations were found in 95.8% of patients, along with their GI manifestations. Dysmotility was found in less than 35% of wireless motility capsule tests. Colon transit time was associated with constipation severity and Bristol Stool Scale. Several GI symptoms were associated with reduced quality of life, anxiety, and work/productivity, but not Fabry severity score. DISCUSSION: This is the largest study of GI manifestations in patients with Fabry disease that characterizes gut motility. We found little association between GI manifestations and motility indices, suggesting that visceral hypersensitivity may be a major driver of symptoms. GI symptoms affect different aspects of patients' lives, yet are not always well-discussed or optimally managed in Fabry disease. Disease severity scores when used for therapeutic decision making do not often include GI symptoms or their impact.

Buspirone for early satiety and symptoms of gastroparesis: A multi-centre, randomised, placebo-controlled, double-masked trial (BESST).

BACKGROUND: Patients with gastroparesis and related disorders have symptoms including early satiety, postprandial fullness and bloating. Buspirone, a 5-HT1 receptor agonist, may improve fundic accommodation. AIM: To determine if buspirone treatment improves early satiety and postprandial fullness in patients with symptoms of gastroparesis. METHODS: This 4-week multi-centre clinical trial randomised patients with symptoms of gastroparesis and moderate-to-severe symptoms of fullness (Gastroparesis Cardinal Symptom Index [GCSI] early satiety/postprandial fullness subscore [ES/PPF]) to buspirone (10 mg orally) or placebo three times per day. The primary outcome was a change in the ES/PPF from baseline to 4 weeks. The primary analysis was per protocol intention-to-treat ANCOVA of between-group baseline vs. 4-week differences (DoD) in ES/PPF adjusted for baseline ES/PPF. Results are reported using both nominal and Bonferroni (BF) p values. RESULTS AND CONCLUSIONS: Ninety-six patients (47 buspirone, 49 placeboes; 92% female, 50% delayed gastric emptying, 39% diabetic) were enrolled. There was no between-groups difference in the 4-week ES/PPF primary outcome: -1.16 ± 1.25 (SD) on buspirone vs -1.03 ± 1.29 (SD) on placebo (mean DoD: -0.11 [95% CI: -0.68, 0.45]; p = 0.69). Buspirone performed better than placebo in patients with severe-to-very severe bloating at baseline compared to patients with none to moderate: (ES/PPF DoD = -0.65 vs. 1.58, pTX*GROUP  = 0.003; pBF  = 0.07). Among individual GCSI symptoms, only bloating appeared to improve with buspirone vs. placebo. CONCLUSIONS: Patients with moderate-to-severe early satiety/postprandial fullness and other symptoms of gastroparesis did not benefit from buspirone treatment to improve the ES/PPF primary outcome compared with placebo. There was a suggestion of the benefit of buspirone in patients with more severe bloating. TRIAL REGISTRATION: ClinicalTrials.gov NCT0358714285.