Choung, Rok Seon

SummaryBackgroundRumination syndrome is a functional gastroduodenal disorder characterised by effortless regurgitation of recently ingested food. Emerging evidence reports duodenal eosinophilic inflammation in a subset, suggesting a shared pathophysiology with functional dyspepsia (FD).AimTo assess the clinical features of rumination syndrome and FD in a community‐based study.MethodsWe mailed a survey assessing gastrointestinal symptoms, diet and psychological symptoms to 9835 residents of Olmsted County, MN, USA in 2017‐2018; diagnostic codes were obtained from linked clinical records. The two disorders were assessed as mutually exclusive in ‘pure’ forms with a separate overlap group, all compared to a control group not meeting criteria for either. Prevalence of associations, and univariate and independent associations with predictors were assessed by logistic regression.ResultsPrevalence of rumination syndrome and FD were 5.8% and 7.1%, respectively; the overlap was 3.83‐times more likely than expected by chance. Independent predictors for rumination (odds ratio (OR), 95% confidence interval (CI)) were female gender (1.79, 1.21‐2.63), smoking (1.89, 1.28‐2.78), gluten‐free diet (1.58, 1.14‐2.19), allergic rhinitis (1.45, 1.01‐2.08) and depression (1.10, 1.05‐1.16). FD was independently associated with female gender, depression, non‐coeliac wheat sensitivity, migraine, irritable bowel syndrome and somatic symptoms. A similar reported efficacy (≥54%) of low fat or dairy‐free diets was found with both disorders (P = 0.53 andP = 1.00, respectively). The strongest independent associations with overlapping FD and rumination syndrome were a history of rheumatoid arthritis (3.93, 1.28‐12.06) and asthma (3.02, 1.44‐6.34).ConclusionRumination syndrome overlaps with FD with a shared risk factor profile, suggesting a common pathophysiology.

INTRODUCTION: Studies on eosinophilic gastroenteritis have identified broad spectrums of disease. We aimed to characterize subtypes of disease and ascertain outcomes of each group. METHODS: This is a retrospective cohort study from a large tertiary medical center including 35 patients diagnosed with eosinophilic gastroenteritis from 2007 to 2018. We defined 2 groups of patients based on clinical and laboratory findings at presentation. Severe disease was defined as having weight loss at time of presentation, hypoalbuminemia at presentation, serosal disease involvement, or anemia at diagnosis. The remaining patients were labeled as mild disease group. We collected and compared demographic data, clinical features, laboratory findings, an allergy history, and disease course of both cohorts. RESULTS: Among 35 patients with eosinophilic gastroenteritis, 18 patients met the criteria for severe disease and 17 patients for mild disease. Of the patients with severe eosinophilic gastroenteritis, 6 (38%) had remission without chronic symptoms, whereas 10 (63%) had chronic symptoms requiring chronic medical therapy. Of the mild group, 12 patients (80%) had disease remission without chronic medications. An allergy history was more common in the severe disease group (83%) compared with the mild disease group (45%). Prednisone and open capsule budesonide were the most commonly used treatment medications in both groups. DISCUSSION: Patients with eosinophilic gastroenteritis may be characterized into 2 forms. Patients with weight loss at time of presentation, hypoalbuminemia at presentation, serosal disease involvement, or anemia at diagnosis were associated with a chronic disease course requiring chronic medications.

Abstract Background Crohn’s disease (CD) is a heterogenous, chronic inflammatory disorder driven by a combination of genetic, environmental, and microbiota-dependent risk factors. Mononuclear phagocytes (MNP) are crucial cells that maintain intestinal homeostasis. An important cytokine for MNP survival and function is granulocyte-macrophage colony stimulating factor (GM-CSF). Interestingly, several studies reported CD-associated genetic risk variants within the GM-CSF receptor and its downstream signaling components. Furthermore, high titers of autoantibodies specific to GM-CSF can be detected in CD patients. Taken together, this data suggests an important role for GM-CSF in abrogation of CD development in a subgroup of patients. Aims This study sought to investigate the function of GM-CSF autoantibodies in CD. Methods We retrospectively quantified and characterized GM-CSF autoantibodies in sera of 220 CD, 200 ulcerative colitis (UC) patients, and 220 healthy controls (HC) sampled at 3 time points prior to disease diagnosis and one time point after diagnosis. ELISA was used to determine GM-CSF autoantibody titers and isotypes followed by in vitro multiplexed mass cytometry (CyTOF) neutralization assays on peripheral blood mononuclear cells. Flow cytometry and CyTOF were used to map the profile of immune cells isolated from inflamed and non-inflamed CD mucosa. Results Our data demonstrates that GM-CSF autoantibodies are specific to CD, significantly elevated up to 7 years prior to diagnosis of disease, and correlate with disease location, severity, and complications at the time of diagnosis. Moreover, in contrast to GM-CSF autoantibodies in pulmonary alveolar proteinosis patients, CD-associated autoantibodies neutralize GM-CSF via specific recognition of post-translational modifications (PTM), affecting MNP function. Removal of PTM enabled GM-CSF to escape autoantibody binding and restored MNP response to GM-CSF in the presence of neutralizing antibodies, indicating a potential therapeutic avenue. Furthermore, we identified group 3 innate lymphoid cells (ILC3) as a major source of GM-CSF in the healthy intestinal tract, suggesting intriguing crosstalk of MNP and ILC3 across the GM-CSF-GM-CSFR axis. Conclusions Our results identify GM-CSF autoantibodies as predictive serological biomarker for CD in a subgroup of patients presenting with severe and complicated form of disease at the time of diagnosis. The presence of GM-CSF autoantibodies precedes the onset of CD by several years and likely abrogates homeostatic immune cell crosstalk involving ILC3 and MNP, suggesting the development of a pre-diseased state in CD patients. Funding Agencies CIHRDr. Edward Ketchum Graduate Scholarship

INTRODUCTION: Untreated symptomatic celiac disease (CD) adversely affects female reproduction; however, the effect of hidden CD autoimmunity is uncertain. METHODS: We identified women who were not previously diagnosed with CD and tested positive for tissue transglutaminase and endomysial antibodies between 2006 and 2011 in a community-based retrospective cohort study. We evaluated (i) the rate of adverse pregnancy outcomes and medical complications of pregnancy in successful singleton deliveries and (ii) reproductive characteristics in seropositive women without a clinical diagnosis of CD and age-matched seronegative women. RESULTS: Among 17,888 women whose serum samples were tested for CD autoimmunity, 215 seropositive and 415 seronegative women were included. We reviewed 231 and 509 live singleton deliveries of 117 seropositive and 250 seronegative mothers, respectively. Menarche and menopausal age, gravidity, parity, and age at first child were similar in seropositive and seronegative women. CD seropositivity was not associated with an increased risk of maternal pregnancy complications. Maternal seropositivity was associated with small for gestational age in boys (OR 3.77, 95% CI: 1.47–9.71; P = 0.006), but not in girls (OR 0.57, 95% CI: 0.15–2.17; P = 0.41). CD serum positivity was not associated with prematurity, small for gestational age (birth weight <10th percentile), or 5-minute Apgar score of less than 7. DISCUSSION: Although underpowered, the present study did not show any difference in reproductive characteristics or rates of adverse pregnancy outcomes in women with and without CD autoimmunity, except for birth weight in male offspring. Larger studies are needed to determine the effects of CD autoimmunity on female reproduction.

Goal: The goal of this study was to estimate the impact of verification bias on the diagnostic accuracy of immunoglobulin A tissue transglutaminase (IgA tTG) in detecting celiac disease as reported by an authoritative meta-analysis, the 2016 Comparative Effectiveness Review (CER). Background: Verification bias is introduced to diagnostic accuracy studies when screening test results impact the decision to verify disease status. Materials and Methods: We adjusted the sensitivity and specificity of IgA tTG reported by the 2016 CER with the proportion of IgA tTG positive and negative individuals who are referred for confirmatory small bowel biopsy. We performed a systematic review from January 1, 2007, to July 19, 2017, to determine these referral rates. Results: The systematic review identified 793 articles of which 9 met inclusion criteria (n=36,477). Overall, 3.6% [95% confidence interval (CI): 1.1%-10.9%] of IgA tTG negative and 79.2.2% (95% CI: 65.0%-88.7%) of IgA tTG positive individuals were referred for biopsy. Adjusting for these referral rates the 2016 CER reported sensitivity of IgA tTG dropped from 92.6% (95% CI: 90.2%-94.5%) to 57.1% (95% CI: 35.4%-76.4%) and the specificity increased from 97.6% (95% CI: 96.3%-98.5%) to 99.6% (95% CI: 98.4%-99.9%). Conclusions: The CER may have largely overestimated the sensitivity of IgA tTG due to a failure to account for verification bias. These findings suggest caution in the interpretation of a negative IgA tTG to rule out celiac disease in clinical practice. More broadly, they highlight the impact of verification bias on diagnostic accuracy estimates and suggest that studies at risk for this bias be excluded from systematic reviews.

Background: Celiac disease (CD) often presents with symptoms of diarrhea and malabsorption, termed classical CD. However, it can also present as nonclassical CD, which is commonly associated with nongastrointestinal symptoms. Studies suggest that nonclassical CD tends to have less severe symptoms than classical CD, which may affect both adherence to a gluten-free diet (GFD) and psychological stress. Therefore, we compared adherence to a GFD and psychological measures, including quality of life (QOL) and somatization, between patients with nonclassical and classical presentations of CD. Methods: Patients at a tertiary care center with biopsy-proven CD, who completed a Talley Bowel Disease Questionnaire and the Short Form-36 at diagnosis and who had been on a GFD for at least 1 year, were included in this study. Patients were further surveyed to assess gastrointestinal symptoms, QOL, Somatization Symptom Checklist (SSC), and adherence to a GFD. Results were compared between patients with classical versus nonclassical CD presentation. Results: Among 122 patients included in this study, 62 had classical CD and 60 had nonclassical CD. At diagnosis, health-related QOL was lower in the classical CD group than in the nonclassical CD group. After following a GFD, both groups had improved QOL after following a GFD, and body mass index significantly increased in both groups. Most subscales of QOL, SSC scores, and adherence to the GFD were similar between the groups, except the Short Form-36 Mental Component summary scores that were still lower in the classical CD (48.4 vs. 52.6 nonclassical CD group; P=0.03). Conclusions: Despite QOL at diagnosis being higher in those with nonclassical CD versus lower in those with classical CD, both groups had improved QOL and achieved a similar QOL after following a GFD.

Summary Background Pregabalin is a calcium channel α2δ ligand that modifies visceral hypersensitivity in IBS patients. Clinical data for pregabalin in IBS are lacking. Aim To test the efficacy of pregabalin on gastrointestinal symptoms in IBS patients. Methods A double‐blind, placebo‐controlled trial was performed. Adults meeting IBS Rome III criteria with ≥3 pain attacks per month were randomised to pregabalin 225 mg vs placebo twice daily for 12 weeks. Questionnaires were completed weekly. The primary endpoint was average pain Bowel Symptom Scale (BSS) scores weeks 9‐12. An intention‐to‐treat analysis of covariance evaluated treatment effects on quantitative endpoints, adjusting for age and gender. Adequate relief and change in pain score were assessed using a chi‐squared test. Results Eighty‐five patients were recruited and randomised. Sample characteristics include: mean age 39.4 (SD = 14.6); 73 (86%) female; 37 (44%) IBS‐D, 29 (35%) IBS‐M, 18 (21%) IBS‐C. The pregabalin arm had lower average pain‐BSS scores weeks 9‐12 (25 vs 42, P = 0.008). Compared with placebo, the overall IBS BSS severity score was lower in the pregabalin arm (26 vs 42, P = 0.009). Differences were observed for the diarrhoea‐BSS and bloating‐BSS scores ( P = 0.049 and 0.016, respectively). No differences between groups were seen for constipation‐BSS scores. Adequate relief was not different between the two arms (46% vs 36%, P = 0.35). 63% pregabalin vs 45% placebo had a change in pain score ≥30 at week 12 from baseline ( P = 0.10). Post‐treatment IBS‐QoL scores did not differ between groups. Conclusion This trial suggests that pregabalin may be beneficial for IBS abdominal pain, bloating and diarrhoea.

Goals: We analyzed demographics, lifestyle patterns, and clinical characteristics of people with celiac disease (CD) and people without CD avoiding gluten (PWAG) to better understand associations with medical conditions and consumer behavior. Background: Clinical significance of CD and gluten avoidance in the general population is incompletely understood. Recently, a high incidence of CD in adolescents with susceptibility genotypes, similar to other autoimmune or allergic disorders, and regional differences in consumer practices of gluten avoidance were reported. Methods: Among 22,277 participants in the National Health and Nutrition Examination Survey 2009-2014, we identified persons with CD by testing CD serology or by both a health care provider diagnosis and adherence to a gluten-free diet. Similarly, PWAG were defined as adherent to a gluten-free diet without a CD diagnosis. Consumer behavior and characteristics of both groups, CD and PWAG were compared with those without these conditions, using survey-weighted generalized logistic regression. Results: Participants with CD considered nutrition very important when grocery shopping and tended to have more constipation and thyroid disease. PWAG tended to spend more money on groceries, purchase organic foods, and check food labels more frequently during grocery shopping. They also reported having more food allergies, asthma, and thyroid disease. Conclusions: Our study confirms that CD and PWAG share comorbidities of autoimmune nature. PWAG had more autoimmune/allergy-related disorders that may be associated with non-celiac gluten sensitivity a self-justifiable reason to be on the diet.