Grover, Madhusudan

Summary Background Patients with gastroparesis and related disorders have symptoms including early satiety, postprandial fullness and bloating. Buspirone, a 5‐HT 1 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, p TX*GROUP = 0.003; p BF = 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.

AbstractBackgroundPatients with gastroparesis (Gp) may need enteral nutrition (EN) or exclusive parenteral nutrition (PN). Among patients with Gp, we aimed to (1) identify the frequency of EN and exclusive PN use and (2) explore characteristics of patients using EN and/or exclusive PN compared with those using oral nutrition (ON), including changes over 48 weeks.MethodsPatients with Gp underwent history and physical examination, gastric emptying scintigraphy, water load satiety testing (WLST), and questionnaires assessing gastrointestinal symptoms and quality of life (QOL). Patients were observed 48 weeks.ResultsOf 971 patients with Gp (idiopathic, 579; diabetic, 336; post–Nissen fundoplication, 51), 939 (96.7%) were using ON only, 14 (1.4%) using exclusive PN, and 18 (1.9%) using EN. Compared with patients receiving ON, patients receiving exclusive PN and/or EN were younger, had lower body mass index, and had greater symptom severity. Patients receiving exclusive PN and/or EN had lower physical QOL but not mental QOL or Gp‐related QOL scores. Patients receiving exclusive PN and/or EN ingested less water during WLST but did not have worse gastric emptying. Of those who had been receiving exclusive PN and/or EN, 50% and 25%, respectively, resumed ON at 48‐week follow‐up.ConclusionsThis study describes patients with Gp requiring exclusive PN and/or EN for nutrition support, who represent a small (3.3%) but important subset of patients with Gp. Unique clinical and physiological parameters are associated with this subset and provide insight into the use of nutrition support in Gp.

AbstractBackgroundThe Rome IV irritable bowel syndrome (IBS) criteria include changes to the description and frequency of abdominal pain. Existing studies have demonstrated a lower prevalence and greater severity in IBS patients identified using Rome IV than Rome III criteria. Our aim was to investigate the prevalence of post‐infection IBS (PI‐IBS) using Rome IV criteria in a population‐based cohort of laboratory‐confirmed C. jejuni infection cases.MethodsThe Minnesota Department of Health (MDH) requires notification of Campylobacter cases and interviews patients to gather information on clinical symptoms. For this study, the Rome IV diagnostic questionnaire was utilized 6–9 months after infection to determine the development of PI‐IBS. The survey responses were analyzed for the prevalence of IBS and symptom severity.Key ResultsSurveys were completed by 391 participants (31% response rate). Twenty‐three patients had pre‐existing IBS, and 18 did not complete enough questions to categorize their case status. Of the 350 remaining participants, 58 (17%) met Rome IV criteria. An additional 47 patients would have met the Rome III IBS criteria for pain frequency, driving the cumulative prevalence to 30%. The mean IBS Symptom Severity Score (IBS‐SSS) in Rome IV patients was significantly higher than in Rome III (p < 0.05). With Rome IV, IBS‐diarrhea was the most common subtype.Conclusions & InferencesRome IV criteria resulted in a 19% lower prevalence of PI‐IBS than earlier reported Rome III‐based prevalence in a similar population. Rome IV defined PI‐IBS patients have greater symptom severity but similar distribution of IBS subtypes.

LINKED CONTENTThis article is linked to Lembo et al paper. To view this article, visit https://doi.org/10.1111/apt.17274

Patients with delayed and normal gastric emptying (GE) had similar symptom profiles during gastric emptying scintigraphy (GES). Idiopathic patients with symptoms of gastroparesis had less gastric retention by GES; but more symptoms after GES meal and after water load satiety test (WLST) compared with diabetic patients. In patients with symptoms of gastroparesis, symptoms after WLST increased with decreasing water consumption. Early satiety and loss of appetite were associated with decreased water consumption during WLST. Thus, impaired accommodation and perhaps visceral hypersensitivity are important in explaining postprandial symptoms in gastroparesis.

Background Immortalized cell lines are conventionally used to examine bacterial virulence and host responses. These models lack heterogeneity, complexity and do not allow interrogation of host specific characteristics. Human intestinal organoids provide a model of human epithelium and allow determination of whether bacterial infections elicit host dependent responses. Objective Determine how gender and stress influence responses to Campylobacter infection using human colonic organoids. Methods Colonic biopsies were collected from 20 volunteers (10/sex), with Hospital Anxiety and Depression Score of <4 (low stress) or >14 (high stress). Crypts were isolated from biopsies. Monolayers were generated, experimentally infected with 3 different clinical isolates of C. jejuni (OD 600 1) and averaged. Bacterial virulence and transepithelial resistance (TER) was measured throughout infection. Proteomics was done 24h post‐infection, with analysis via 1D‐LC‐MS using an Orbitrap Eclipse. Data was processed with MS2 ID pipeline MyriMatch‐IDPicker and proteins FDR<0.1 considered significant. Results Colonoid cultures were generated from 75% of volunteers. C. jejuni strains attachmed and invaded all colonoids. Greater bacterial attachment was seen on high stress volunteer colonoids compared low stress (0.08 ± 0.11 vs. 0.03 ± 0.08 CFU/starting inoculum for males, 0.015 ± 0.036 vs. 0.014 ± 0.014 for females, p<0.05 for both) and on high stress males compared to females (p<0.001). Colonoids from high stress volunteers had a significant drop in TER 24h post‐infection compared to non‐infected controls (42.1 ± 30.7 vs 125.2 ± 62.4, % baseline, p<0.05). Proteomic analysis showed minimal differences between high and low stress or between female and male colonoids at baseline (4 and 9 proteins respectively). Upon infection 195 proteins were differentially abundant with 161 increased in stressed organoids (FDR<0.1). Increased apoptotic pathway activation and cellular reorganization; pro‐apoptotic death‐associated protein‐kinase 3 (DAPK3), and DNA damage response serine/threonine‐protein kinase protein (TAOK3) were seen. Gene set enrichment analysis (GSEA) showed increased interferon alpha and beta signaling, IL‐1 and IL‐17 responses and MHC1/2 antigen processing in high stress infected monolayers (FDR<0.1). No differences between male high and low stress organoids post infection. In contrast, 1289 proteins were differentially abundant between high and low stress females with 84% up in stressed organoids. IL‐1 and IL‐12 signaling was up in high stress female organoids (FDR<0.1). Conclusions Colonoid monolayers can be developed from human volunteers and used to evaluate host pathogen interactions. Colonoid cultures highlight variability in C. jejuni infectivity and host responses; with robust C. jejuni virulence seen with high stress male individuals and the greatest change in proteomic profile in response to infection in high stress females. These findings demonstrate utility of colonoids and provide a platform to study personalized host responses to infection.

AbstractBackgroundPatients with gastroparesis (GP) and functional dyspepsia (FD) have similar symptoms, but the pathophysiology of postprandial symptoms remains uncertain.AimsTo compare symptoms and gastric myoelectrical activity (GMA) after liquid and solid test meals in patients with GP and FD.MethodsPatients enrolled in the Gastroparesis Clinical Research Consortium Registry were studied. Clinical characteristics were measured with standard questionnaires. GP was determined by 4‐h solid‐phase gastric scintigraphy. GMA was measured using electrogastrography before and after ingestion of a water load or nutrient bar on separate days. Symptoms were measured on visual analog scales. GMA responses to the water load for individual patients were also determined.Results284 patients with GP and 113 with FD were identified who ingested both test meals. Patients with GP and FD had similar maximal tolerated volumes of water [mean (SD) 378 (218) ml vs. 402 (226) ml,p = 0.23] and reported similar intensity of fullness, nausea, bloating, and abdominal discomfort after the test meals. Twenty‐six percent and 19% of the patients with GP and FD, respectively, ingested subthreshold (<238 ml) volumes of water (p = 0.15). Gastric dysrhythmias were recorded in 66% of the GP and 65% of the FD patients after the water load. Symptoms and GMA were similar in both groups after ingestion of the nutrient bar.ConclusionThe similarity in GMA responses and symptoms after ingestion of solid or liquid test meals suggests GP and FD are closely related gastric neuromuscular disorders.

INTRODUCTION: Treated patients with celiac disease (CeD) and nonceliac gluten sensitivity (NCGS) report acute, transient, incompletely understood symptoms after suspected gluten exposure. To determine whether (i) blinded gluten exposure induces symptoms, (ii) subjects accurately identify gluten exposure, and (iii) serum interleukin-2 (IL-2) levels distinguish CeD from NCGS subjects after gluten exposure. METHODS: Sixty subjects (n = 20 treated, healed CeD; n = 20 treated NCGS; n = 20 controls) were block randomized to a single, double-blind sham (rice flour) or 3-g gluten challenge with 72-hours follow-up. Twelve serial questionnaires (100 mm visual analog scale; pain, bloating, nausea, and fatigue) and 10 serial plasma samples were collected. Mucosal permeability was assessed using both urinary lactulose- 13 C mannitol ratios and endoscopic mucosal impedance. RESULTS: Thirty-five of 40 (83%) subjects with CeD and NCGS reported symptoms with gluten (8 CeD, 9 NCGS) and sham (9 CeD, 9 NCGS) compared with 9 of 20 (45%) controls after gluten (n = 6) and sham (n = 3). There was no significant difference in symptoms among groups. Only 2 of 10 subjects with CeD and 4 of 10 NCGS identified gluten, whereas 8 of 10 subjects with CeD and 5 of 10 NCGS identified sham. A significant plasma IL-2 increase occurred only in subjects with CeD after gluten, peaking at 3 hours and normalizing within 24 hours postchallenge despite no significant intestinal permeability change from baseline. DISCUSSION: Symptoms do not reliably indicate gluten exposure in either subjects with CeD or NCGS. IL-2 production indicates a rapid-onset gluten-induced T-cell activation in CeD despite long-standing treatment. The effector site is unknown, given no increased intestinal permeability after gluten.

LINKED CONTENTThis article is linked to Grover et al and Elwing & Sayuk papers. To view these articles, visit https://doi.org/10.1111/apt.16591 and https://doi.org/10.1111/apt.16603