Citations

ABSTRACT Background In healthy controls, higher gastric accommodation (GA) was associated with slower gastric emptying (GE) of solids. Aims In patients with gastroparesis: (1) To investigate the association between GA and GE of solids. (2) To assess the prevalence of abnormally high GA. Methods An electronic medical records (EMR) review (2010–2024) was conducted on 745 adult patients with measured GA following 300 kcal Ensure using SPECT, and scintigraphy‐based GE of solids (320 kcal, 30% fat, egg meal). Among these patients, 284 had gastroparesis (GE < 25% emptied at 2 h or < 75% emptied at 4 h). Spearman correlation analysis examined associations between GA volume or ratio and GE at 1, 2, and 4 h, and GE T 1/2 . Results Weak positive correlations were observed between GA volume and GE of solids % at 1 and 2 h (respectively R s = 0.148, p = 0.0234, and R s = 0.121, p = 0.042). In addition, there was a correlation between GA ratio and GE of solids % at 2 h ( R s = 0.143, p = 0.0160). However, there were no significant correlations of GA with GE % at 4 h or GE T 1/2 . Among the 284 patients with gastroparesis, we had documented increased GA, assessed by postprandial minus preprandial gastric volume (> 640 mL), in 7.75%, and increased GA by GA ratio > 3.85 in 22.9%. Conclusions Among patients with gastroparesis, higher GA is associated with accelerated GE of solids in the first 2 h, though the effect size is small. There is no significant effect on delayed GE at 4 h or GE T 1/2 .

ABSTRACTBackgroundThe intestinal barrier protects humans from potentially deleterious ingested material. It consists of several components: commensal organisms, mucus, and transepithelial pathways, and immune functions.AimsTo review, with major focus on human studies, the methods to measure intestinal barrier function in vivo and the impaired intestinal barrier function in non‐inflammatory conditions, and the deleterious or beneficial effects of dietary components on the intestinal barrier.MethodsPUBMED literature search was intentionally focused, when possible, on human studies conducted in vivo.ResultsAlthough many gastrointestinal, rheumatological, and degenerative neurological diseases are attributed to impaired intestinal barrier function, often termed “leaky gut,” methods of accurate measurement of intestinal barrier function in vivo in humans are still being developed. In vivo measurements provide an overall assessment of barrier function at a whole organ level, whereas ex vivo or in vitro measurements using mucosal biopsies address mechanistic information at the cellular level. Several dietary components are detrimental to the barrier, including ethanol, fat, sugars, gliadin, food additives, emulsifiers, and microbial transglutaminase. Conversely, dietary components improving barrier function include fibre and metabolites such as short‐chain fatty acids, anthocyanins, polyphenols, vitamins (such as A and D), zinc, specific amino acids (such as glutamine) and probiotics.ConclusionsCurrently, data are not exclusively from human studies, and research is needed to corroborate observations in animals or further validate in humans. There are several practical dietary approaches that can be instituted for restoration of the intestinal barrier in humans.

ABSTRACT Background Several genetic syndromes that affect nerve development and functioning may involve the enteric nervous system and present clinically as dysmotility syndromes, typically in childhood. Aim To review the enteric neuromuscular manifestations, predominantly observed in adults, of neurofibromatosis type I at a tertiary referral center. Methods We conducted a medical records review at the Mayo Clinic and documented clinical manifestations and findings on radiology, pathology, and specialized motility tests of the esophagus, stomach, colon, and rectal evacuatory functions. The tests included scintigraphic gastrointestinal and colonic transit measurements, intraluminal esophageal, gastrointestinal, colonic, and anorectal manometry, and balloon expulsion test. Results Among 2406 with documented NF1, the gastrointestinal manifestations were obstruction or dysmotility, seen in 2% of the cohort. Thirteen patients had small bowel or colonic obstructions: 4 gastrointestinal stromal tumors, 3 malignant peripheral nerve sheath tumors, 3 neurofibromas, 1 diffuse ganglioneuromatosis, 1 schwannoma, and 1 inflammatory fibroid polyp. In addition, 38 patients had abnormal gut motility, including esophageal achalasia or spasm, delayed gastric emptying, slow colonic transit, and dyssynergic defecation. Gastric, small bowel, and colonic manometry were characterized by normal amplitude incoordinated contractions suggestive of neuropathy. In the few resected specimens, myenteric plexus proliferation or diffuse ganglioneuromatosis was identified histologically. Conclusions In addition to mechanical obstruction, typically due to benign tumors affecting smooth muscle or components of nerve (sheath or nerve fiber), patients with NF1 may present with dysmotility syndromes such as gastroparesis, slow colonic transit, or global dysmotility. Neuropathic dysmotility in NF1 can be identified by manometry and by histological evidence of myenteric plexus proliferation or diffuse ganglioneuromatosis.

INTRODUCTION: Altered intestinal permeability (IP) is implicated in multiple gastrointestinal and systemic disease conditions; an experimental model of perturbed IP in healthy subjects is needed. Traditional approaches to perturbing IP include use of nonsteroidal anti-inflammatory drugs. METHODS: We conducted a single-center, randomized, placebo-controlled pilot study of dose-related effects of castor oil (CO) (and its ingredient ricinoleic acid) at 750, 1,500, or 3,000 mg daily doses on IP. Permeability was assessed using validated 13 C-mannitol and lactulose urine excretion at 0–2, 8–24, and 0–24 hours after oral administration. RESULTS: Permeability analysis across all groups demonstrated significant difference among the groups for 0–2 hours 13 C-mannitol, 0–24 hours 13 C-mannitol, and borderline significant difference for 2–8 hours 13 C-mannitol ( P = 0.060) and 0–24 hours lactulose ( P = 0.056). Direct comparison of 3,000 mg CO vs placebo ( t test) demonstrated higher excretion of 13 C-mannitol and lactulose at 0–2, and 0–24 hours, and lactulose at 2–8 hours. DISCUSSION: CO may perturb small intestinal and colonic permeability in healthy adults.

ImportanceDirect immunofluorescence (DIF) testing has been an important ancillary tool for the diagnosis of various inflammatory mucocutaneous conditions for more than 50 years. Current DIF test panels are based on historical clinical descriptions; few studies have rigorously addressed preanalytical, analytical, and/or postanalytical aspects, and even fewer have been replicated or validated. Recent unresolved key issues include whether DIF testing and test panels should be triaged or truncated based on clinical indication or histopathologic findings.ObjectiveTo assess levels of consensus regarding practical aspects of DIF testing among immunodermatology testing specialists in the US.Design, Setting, and ParticipantsUsing modified Delphi methods with a priori characterized criteria, a survey containing 54 statements pertaining to DIF testing was created and distributed to assess consensus. Statements not initially reaching consensus were discussed in 2 live virtual sessions, which were supplemented by relevant literature review and free-text survey comments. These statements were then reassessed in a second survey. Immunodermatology testing specialists in US academic institution–based and independent laboratories were invited based on serving as immunodermatology laboratory medical directors, authoring pertinent literature, or delivering relevant talks at major conferences or by referral. The first survey was conducted from January to February 2024, and the second survey was conducted from March to April 2024.Main Outcomes and MeasuresThe primary measured outcome was degree of consensus for various DIF testing practice, including DIF testing triage by histopathology/dermatopathology findings and DIF testing panel tailored truncations by clinical indication.ResultsA total of 23 respondents to the survey invitation had a mean (SD) of 18.5 (11.1) years and median (range) of 20.0 (1.5-46.0) years in immunodermatology laboratory practice. Consensus was achieved for 46 of 54 statements (85.2%) in the initial survey and for an additional 4 statements in the second survey (50 of 54 [92.6%]). Strong consensus was found against tailored truncation of DIF panel based on the clinical indication in the first survey round. The general acceptability of triaging specimens for DIF testing based on histopathology findings remained without consensus after both surveys.Conclusions and RelevanceOverall, participating US specialists in immunodermatology laboratory testing agreed on many practical aspects of DIF testing, including matters not queried previously. The findings also revealed areas of continued controversy and identified issues for prioritized future study.

Lay Summary This article looks at how changes in bile acids and gut bacteria might contribute to chronic pouchitis, a condition that can develop after surgical removal of the colon and creation of a J-pouch for people with inflammatory bowel disease. The goal is to better understand pouchitis and find treatments to improve patients’ health.

Abstract Background and Aims Inflammatory bowel disease (IBD) is associated with altered mucus and increased intestinal permeability (IP). Prior reports on permeability in IBD typically used lactulose-to-mannitol ratio (LMR). Food contamination with 12C-mannitol is a significant potential confounder in IP assessment. We aimed to compare small intestinal (SI) and colonic (COL) permeability in IBD, both active (ACT) and in remission (REM), to normal healthy volunteers (NHV). Methods Inflammatory bowel disease activity was based on Simple Endoscopic Score for Crohn’s Disease (SES-CD) and Mayo endoscopy score for ulcerative colitis (UC). We performed 24-hour IP test using 100 mg 13C-mannitol and 1000 mg lactulose with urine collected during 0-2, 2-8, and 8-24 hours. The primary endpoint was mg excretion of 13C-mannitol and lactulose during 2-24 hours reflecting SI and COL permeability. Results Among 17 CD patients, 7 were ACT (SES-CD &gt;6), and 10 REM (SES-CD 0-2). Among 20 UC patients, 10 had ACT (Mayo score 2-3), and 10 REM (Mayo score 0-1). Urinary excretions over 2-24 hours were higher for IBD than NHV: 13C-mannitol (13.8 [IQR 8.8, 18.7] NHV; 18.4 [15.6, 29.9] REM; 19.7 [13.8, 23.6] ACT, P = .003) and lactulose (1.8 [1.3, 3.1] NHV; 3.6 [2.0, 5.0] REM; 3.5 [2.0, 6.6] ACT, P = .006). There was no difference between ACT and REM for any timed urine collection. LMR at 2-24 hours (or 2-8 and 8-24 hours) were not statistically significant between the 3 groups (0.014 [0.010, 0.021] NHV; 0.016 [0.010, 0.023] REM; 0.016 [0.012, 0.038] ACT, P = .237). Conclusions Intestinal permeability is increased in IBD using validated in vivo assay relative to NHV; increased IP in IBD persists during remission.

Objective: To develop and validate 2 predictive models, the Diabetes Remission Index (DRI) and the Weight loss–adjusted DRI (W-DRI), for assessing type 2 diabetes (T2D) remission following metabolic and bariatric surgery (MBS). Background: MBS, including Roux-en-Y gastric bypass and sleeve gastrectomy, is highly effective in achieving T2D remission, but outcomes vary across populations. Predicting remission remains critical for individualized patient care and optimizing surgical outcomes. Existing tools focus on general outcomes, and a specific model incorporating weight loss data has been lacking. Methods: This multicenter, retrospective cohort study included patients with T2D and overweight/obesity (body mass index: ≥27 kg/m 2 ) who underwent Roux-en-Y gastric bypass or sleeve gastrectomy between 2008 and 2018. Institution 1 (I-1) data (n = 503) were used to develop and internally validate the models, whereas Institution 2 (I-2) data (n = 409) were used for external validation. The DRI model incorporated preoperative variables, and the W-DRI model, in addition, included postsurgical weight loss. Predictive accuracy was assessed using area under the Receiver Operating Characteristic curve [area under the curve (AUC)], calibration plots, and stratified analyses. Results: In I-1, 44.7% of patients achieved T2D remission, with a DRI model AUC of 0.80. In I-2, 52.6% achieved remission, with a model AUC of 0.78. Incorporating weight loss improved W-DRI predictive accuracy (AUC: 0.82 in I-1, 0.79 in I-2). Calibration plots demonstrated strong agreement between predicted and observed remission rates. An online DRI and W-DRI calculator is available through the Mayo Clinic webpage (https://newsnetwork.mayoclinic.org/dri-calculator/). Conclusions: The DRI and W-DRI models accurately predict T2D remission post-MBS, enabling personalized patient care and informed decision-making. Further validation across diverse populations is warranted.

ABSTRACTBackgroundSurrogate endpoints such as laboratory parameters that are not direct measurements of, but predict, clinical benefit are approved by regulatory agencies for initial proof of efficacy. No surrogate endpoints are approved for disorders of gut–brain interaction.AimTo assess the correlation of scintigraphic colonic transit (CT) with response rates according to patient‐reported symptom‐based endpoints (composite/global symptoms, abdominal pain or stool frequency/consistency) in irritable bowel syndrome (IBS) or chronic idiopathic constipation (CIC).MethodsWe reviewed available data from, randomised controlled trials (RCTs) reporting effects on CT at 24 h and 48 h with drug versus placebo and extracted the difference in the proportions responding to drug or placebo, using rates from individual RCTs or from meta‐analyses when more than one RCT existed for a drug. We analysed associations between differences (drug vs. placebo) in CT and in response rates using Spearman correlation. Additional analyses of CT at 24 h with composite/global symptom or pain endpoints were performed with exclusion of alosetron (the only drug slowing CT).ResultsCT at 24 h correlated significantly with composite/global symptom endpoints (Rs = −0.755, p = 0.021). CT correlated with stool frequency or consistency (at 24 h, Rs = 0.506, p = 0.074; at 48 h, Rs = 0.631, p = 0.026). CT at 24 h did not correlate with abdominal pain (Rs = −0.054, p = 0.843). With the exclusion of alosetron data, CT at 24 h was non‐significantly correlated with the composite/global symptom endpoint (Rs = −0.667, p = 0.073), but not with abdominal pain (Rs = 0.377, p = 0.419).ConclusionScintigraphic CT measurement fulfils the expectation of a surrogate endpoint for symptom‐based outcomes, particularly in IBS‐D or IBS‐C and CIC.