Gluten-related Disorders From Bench to Bedside.

Celiac disease, non-celiac gluten sensitivity, and wheat allergy comprise 3 of the main conditions with wheat- and gluten-containing foods as the symptom trigger. Distinguishing between these entities can be daunting. In this review, we compare and contrast celiac disease, non-celiac gluten sensitivity, and wheat allergy to allow clinicians to determine which diagnosis fits their patient to facilitate high-quality management and longitudinal care.

Maternal, obstetrical, and neonatal outcomes in celiac disease.

OBJECTIVES: Some studies have suggested a link between celiac disease (CD) and adverse maternal, obstetrical, and neonatal outcomes. Using a large database, we evaluated the effect of CD on pregnancy outcomes. METHODS: We conducted a retrospective cohort study using the National Inpatient Sample (NIS) of all deliveries from 2015 to 2019 in the United States. Using ICD-10 codes, we identified pregnant patients who had CD and those who did not. A multivariate logistic regression was used to generate odds ratios (ORs) with 95% confidence intervals (CIs) for maternal, obstetrical, and neonatal outcomes. RESULTS: Of 12,039,222 deliveries between 2015 and 2019, there were 10,555 births in women with CD. Pregnant women with CD were more likely to be white and older compared to those without CD. Pregnant women with CD were significantly more likely to carry a diagnosis of gestational hypertension (OR 1.26; 95% CI 1.04-1.52), preeclampsia (1.28; 1.08-1.53), and severe preeclampsia (1.62; 1.25-2.09). They were less likely to have a full-term uncomplicated delivery (OR 0.11; 95% CI, 0.05-0.20), while being more likely to require device-assisted delivery (1.25; 1.04-1.50) and sustain 3rd or 4th degree vaginal lacerations (1.56; 1.21-2.02). Babies of pregnant women with CD were more likely to be small for gestational age (SGA) (OR 1.29; 95% CI 1.03-1.61). CONCLUSIONS: CD in pregnancy appears to be associated with increased adverse maternal, obstetrical, and neonatal outcomes. Clinicians should discuss these increased risks with CD patients who are planning to conceive.

A Dedicated Celiac Disease Program Improves Celiac Quality Care Metrics and Short-Term Outcomes in Real Life.

BACKGROUND AND AIMS: Dedicated multidisciplinary programs in gastroenterology are emerging with the goal to improve care. There is little information about the effects of a celiac disease program on disease-related quality care metrics and outcomes. We aimed to compare quality care metrics, symptom resolution, and serological response among patients diagnosed and treated in a celiac disease program with a standard of care cohort. METHODS: We performed a retrospective cohort study with adult celiac disease patients. We divided patients into two groups: celiac disease patients treated in our program and those treated by gastroenterologists not affiliated with the program (standard of care). We abstracted data from electronical medical records and compared frequency at which guideline-driven quality care metrics were obtained, assessed symptom resolution, and serological response based on IgA anti-tissue transglutaminase levels. RESULTS: We included 340 patients, 120 in the celiac disease program (89 women) and 220 (166 women) in the standard of care. Frequency of quality care metrics implementation in program patients was significantly greater for all variables (p < 0.0005). Diarrhea resolved in 38/46 (82.6%) in the CD program and 63/98 (64.2%) in the standard of care after starting a gluten-free diet (p = .025); bloating also resolved significantly more often in the former (26/34) than the latter (31/58; p = 0.03). Otherwise, there were no significant differences in resolution of clinical symptoms or serological response. CONCLUSION: A celiac disease program improves celiac-related quality care metrics and may improve outcomes such as diarrhea resolution compared to standard of care.

Increased Risk of Herpes Zoster Infection in Patients with Celiac Disease 50 Years Old and Older.

BACKGROUND: Celiac Disease (CD) is associated with increased susceptibility to certain bacterial and viral infections. Herpes zoster (HZ) is a viral infection that can be prevented by immunization. In the US, the vaccine is recommended for adults ≥ 50 or ≥ 19 with certain at-risk conditions, not including CD. AIMS: We aimed to determine if adult patients aged < 50 or ≥ 50 years with CD had a higher risk of developing HZ. METHODS: We designed a retrospective cohort study. CD was defined as patients with the ICD-10 code for CD and positive Celiac serology. Patients with negative serology and lacking CD ICD-10 codes served as controls. Patients who had HZ before CD diagnosis were excluded. We formed two sub-cohorts, those aged < 50 (cohort 1) and aged ≥ 50 years (cohort 2), and evaluated HZ infection at 10-year follow-up. To account for confounding variables, we performed 1:1 propensity score matching (PSM). RESULTS: Following PSM, cohort 1 had 6,826 CD patients, and cohort 2 had 5,337 CD patients and respective matched controls. After ten years of follow-up, in cohort 1, 62 CD patients developed HZ versus 57 controls, RR: 1.09 (CI: 0.76-1.56, p-value = 0.64). In cohort 2, 200 CD patients developed HZ versus 159 controls, RR: 1.2 (CI: 1.02-1.54, p-value = 0.03). CONCLUSION: There was no significant difference in the likelihood of getting HZ in CD patients < 50, although CD patients ≥ 50 had a modestly increased risk. Our findings do not support routine early vaccination for HZ in CD, and the vaccine should be offered at age 50.

Increased Risk of Hospitalization in Celiac Disease With COVID-19 Infection Is Mitigated by Vaccination.

BACKGROUND: We sought to describe clinical characteristics of celiac disease (CD) patients infected with coronavirus disease 2019 (COVID-19) and estimate hospitalization risk, intensive care unit (ICU) requirement, mortality, and thrombosis, and the impact of vaccination on these outcomes. METHODS: We performed a single-center, retrospective cohort study comparing biopsy-proven CD patients with a matched sample of non-CD (referent) patients diagnosed with COVID-19 between March 2020 and January 2022. Matching ensured 2 referent patients for every 1 CD patient by age, sex, ethnicity, and COVID-19 diagnosis date. We also adjusted for general and celiac-specific comorbidity. The primary outcome was hospitalization. Secondary outcomes included ICU requirement, mortality, and thrombosis. We also compared these outcomes between vaccinated and unvaccinated individuals. RESULTS: We included 330 patients: 110 with CD (mean age 47 years, 83% female) and 220 matched referents. Hospitalization occurred in 27 CD patients (24%) and 25 referent patients (11%) (hazard ratio, 2.10; 95% confidence interval, 1.21-3.65; P = .009). Vaccination was associated with significantly decreased risk of hospitalization (hazard ratio, 0.53; 95% confidence interval, 0.31-0.93; P = .026). Four unvaccinated CD patients and 2 unvaccinated referent patients required ICU. No mortality occurred among CD patients, and 2 referent patients died. No thrombosis occurred in either group. CONCLUSIONS: CD patients with COVID-19 have a higher risk of hospitalization compared with non-CD referents. This risk is mitigated by vaccination in CD patients as it is in non-CD referents. ICU requirement occurred only in unvaccinated CD patients, and no CD patient died. Vaccination against COVID-19 should be strongly recommended in patients with CD as it is for non-CD patients in the general population.

Relationship between gluten availability and celiac disease prevalence: A geo-epidemiologic systematic review.

Celiac disease is a global disease requiring genetic susceptibility and gluten exposure to trigger immune-mediated enteropathy. The effect of the degree of gluten-containing grain availability on celiac disease prevalence is unknown. Our objective was to compare country-based gluten availability to celiac prevalence using a systematic literature review. We searched MEDLINE, Embase, Cochrane, and Scopus until May 2021. We included population-based serum screening with confirmatory testing (second serological study or small intestine biopsy) and excluded specific, high-risk, or referral populations. We determined country-specific gluten availability using the United Nations food balance for wheat, barley, and rye. Human leukocyte antigen (HLA) frequencies were obtained from allelefrequencies.net. The primary outcome was association between gluten-containing grain availability and celiac disease prevalence. Generalized linear mixed models method with Poisson's link was used for analysis. We identified 5641 articles and included 120 studies on 427 146 subjects from 41 countries. Celiac disease prevalence was 0-3.1%, median 0.75% (interquartile range 0.35, 1.22). Median wheat supply was 246 g/capita/day (interquartile range 214.8, 360.7). The risk ratio (RR) for wheat availability on celiac disease was 1.002 (95% confidence interval [CI]: 1.0001, 1.004, P = 0.036). A protective association was seen with barley, RR 0.973 (95% CI: 0.956, 0.99, P = 0.003), and rye, RR 0.989 (95% CI: 0.982, 0.997, P = 0.006). The RR for gross domestic product on celiac disease prevalence was 1.009 (95% CI: 1.005, 1.014, P < 0.001). The RR for HLA-DQ2 was 0.982 (95% CI: 0.979, 0.986, P < 0.001), and that for HLA-DQ8 was 0.957 (95% CI: 0.950, 0.964, P < 0.001). In this geo-epidemiologic study, gluten-containing grain availability showed mixed associations with celiac disease prevalence.

Self-Reported Gluten Intolerance Is Prevalent, but Not All Gluten-Containing Foods Are Equal.

BACKGROUND: Celiac disease prevalence approaches 1%; more suffer from non-celiac gluten sensitivity. AIMS: Our goal was to estimate the prevalence of gluten intolerance. METHODS: We invited US adults (18-80 years) via Amazon's mechanical Turk to complete an online survey. Gluten intolerance was defined as self-reported intolerance to wheat, barley, rye, flour, or pasta. Those with celiac disease were not excluded. RESULTS: We collected 2133 responses. Rate of gluten intolerance was 5.1% (95% CI 4.2-6.1%). Each food had different rates: wheat 4.8%, flour 1.2%, pasta 0.9%, barley 0.8%, and rye 0.8%. Among 108 adults reporting any gluten intolerance, 62.0% selected only wheat, 10.2% selected all gluten-containing grains excluding pasta and flour, and 5.6% selected all gluten-containing products. Overall intolerance to any food was 24.8% (95% CI 23.0-26.6%). Wheat was second only to lactose. CONCLUSIONS: Self-reported intolerance to wheat, but not all gluten-containing foods, is common. Findings may suggest poor knowledge of gluten-containing foods or that self-perceived non-celiac gluten sensitivity is prevalent.

Bi-directional Relationship Between Celiac Disease and Liver Chemistries: A Systematic Review and Meta-Analysis.

AIMS: Previous studies have reported conflicting results regarding prevalence of elevated LC (2-70%) in celiac disease (CD). This systematic review and meta-analysis assessed the prevalence of elevated LC at time of CD diagnosis and associated response to GFD. We also report the prevalence of CD in patients with unexplained elevation of LC. METHODS: Studies assessing LC (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) in CD patients were eligible. Studies with < 50 cases or in pediatric populations were excluded. RESULTS: In total, 20 studies assessing prevalence of elevated LC in 4,265 participants with newly diagnosed CD (mean age = 35.6 ± 6.5 years, 69.8% female) were included. Pooled prevalence of elevated LC was 18.7% (95% CI 13.8-24.8; I2 = 95%). Normalization of elevated LC was seen in 83.1% (95% CI 73.4-89.7; I2 = 79%, 11 studies) of patients after GFD. On meta-regression, age at CD diagnosis, gender, and Marsh grading were not associated with elevated LC. Among 979 participants (7 studies) with unexplained elevation of LC, pooled seroprevalence and biopsy-proven CD was 6.4% (95% CI 2.9-10.3, I2 = 71%) and 4.5% (95% CI 2.6-7.7, I2 = 67%), respectively. CONCLUSION: Elevated LC are seen in approximately one-fifth of patients at CD diagnosis with majority normalizing after GFD. Age, gender, and degree of intestinal damage are not predictive of elevated LC. In the appropriate clinical scenario, liver tests should be serially monitored in CD reserving workup for additional causes after a trial of GFD. Patients with unexplained elevation of liver tests should be screened for celiac disease.

Clinical Presentation of Small Intestinal Bacterial Overgrowth from Aerodigestive Tract Bacteria Versus Colonic-Type Bacteria: A Comparison Study.

BACKGROUND: Small Intestinal Bacterial Overgrowth (SIBO) is a heterogenous syndrome from excessive bacteria in the small intestine lumen. It is unknown if differences in type of bacterial overgrowth lead to differences in symptoms. METHODS: Patients with suspected SIBO were recruited prospectively. Exclusion criteria were probiotics, antibiotics, or bowel prep in preceding 30 days. Clinical characteristics, risk factors, and labs were collected. Proximal jejunal aspiration via upper enteroscopy was performed. Aerodigestive tract (ADT) SIBO was defined as > 105 CFU/mL of oropharyngeal and respiratory bacteria. Colonic-type SIBO was defined as > 104 CFU/mL of distal small bowel and colon bacteria. Aims were to compare symptom profiles, clinical complications, labs, and underlying risk factors between ADT and colonic-type SIBO. KEY RESULTS: We consented 166 subjects. Aspiration was not obtained in 22 and SIBO was found in 69 (49%) of 144 subjects. Daily abdominal distention trended towards more prevalent in ADT SIBO versus colonic-type SIBO (65.2% vs 39.1%, p = 0.09). Patient symptom scores were similar. Iron deficiency was more prevalent in ADT SIBO (33.3% vs 10.3%, p = 0.04). Subjects with colonic-type SIBO were more likely to have a risk factor for colonic bacteria colonization (60.9% vs 17.4%, p = 0.0006). Subjects with ADT SIBO were more likely to have a risk factor for diminished gastric acid (91.3% vs 67.4%, p = 0.02). CONCLUSIONS & INFERENCES: We found differences in iron deficiency and underlying risk factors between ADT and colonic-type SIBO. However, distinct clinical profiles remained elusive. Future research is needed to develop validated symptom assessment tools and distinguish cause from correlation.

Associations of Food Intolerance with Irritable Bowel Syndrome, Psychological Symptoms, and Quality of Life.

BACKGROUND & AIMS: The impact of different types of food intolerance on gastrointestinal symptoms and quality of life (QOL) is poorly understood. We aimed to investigate associations of food intolerance and type of intolerance with irritable bowel syndrome (IBS), health-related QOL, and psychological symptoms. METHODS: We conducted an observational study of United States-based adults through an online survey. Demographics, culprit foods, symptoms, medical evaluation, Rome IV criteria for IBS, health-related QOL (Short-Form Health Survey 12), and anxiety and depression scores (Hospital Anxiety and Depression Scale) were collected in participants with self-reported food intolerance (lactose, non-lactose food, lactose plus food intolerance), and controls with no intolerance. Univariable associations of group with study endpoints were analyzed with the Kruskal-Wallis and Pearson χ2 or Fisher exact test. Multivariable comparisons were analyzed by logistic and linear regression. RESULTS: A total of 197 patients with (59 lactose, 61 non-lactose food, 77 lactose plus food intolerance) and 273 patients without intolerance participated. Lactose, wheat, and eggs were the most common food triggers. Gas (54.2%), abdominal pain (40.2%), and diarrhea (37.3%) were frequently reported symptoms of food intolerance. Reactions caused 57.8% to eliminate the food. Rates of IBS, abnormal anxiety scores, and abnormal depression scores were highest in lactose plus food intolerance; Short-Form Health Survey 12 scores were lowest in lactose plus food intolerance. Multivariable analyses revealed all intolerance subgroups were more likely to have IBS than controls. CONCLUSIONS: Food intolerance is associated with IBS, anxiety, depression, and decreased health-related QOL and frequently leads to food elimination. Adults with lactose and lactose plus food intolerance have higher rates of IBS, increased psychological symptoms, and poorer QOL.

Latitude and Celiac Disease Prevalence: A Meta-Analysis and Meta-Regression.

BACKGROUND & AIMS: The latitudinal gradient effect is described for several autoimmune diseases including celiac disease in the United States. However, the association between latitude and global celiac disease prevalence is unknown. We aimed to explore the association between latitude and serology-based celiac disease prevalence through meta-analysis. METHODS: We searched MEDLINE, Embase, Cochrane, and Scopus databases from their beginning through June 29, 2018, to identify screening studies that targeted a general population sample, used serology-based screening tests, and provided a clear location from which we could assign a latitude. Studies were excluded if sampling was based on symptoms, risk factors, or referral. Study selection and data extraction were performed by independent reviewers. The association measures between latitude and prevalence of serology-based celiac disease were evaluated with random-effects meta-analyses and meta-regression. RESULTS: Of the identified 4667 unique citations, 128 studies were included, with 155 prevalence estimates representing 40 countries. Celiac disease was more prevalent at the higher latitudes of 51° to 60° (relative risk [RR], 1.62; 95% CI, 1.09-2.38) and 61° to 70° (RR, 2.30; 95% CI, 1.36-3.89) compared with the 41° to 50° reference level. No statistically significant difference was observed at lower latitudes. When latitude was treated as continuous, we found a statistically significant association between CD prevalence and latitude overall in the world (RR, 1.03, 95% CI, 1.01-1.05) and a subregional analysis of Europe (RR, 1.05; 95% CI, 1.02-1.07) and North America (RR, 1.1; 95% CI, 1.0-1.2). CONCLUSIONS: In this comprehensive review of screening studies, we found that a higher latitude was associated with greater serology-based celiac disease prevalence.

Relationships of Intestinal Lactase and the Small Intestinal Microbiome with Symptoms of Lactose Intolerance and Intake in Adults.

BACKGROUND: Approximately two-thirds of adults are genetically predisposed to decreased lactase activity after weaning, putting them at risk of lactose intolerance. However, symptoms are a poor marker of lactose maldigestion. AIMS: We assessed association between self-reported lactose intolerance and intestinal lactase, lactose intake, and the small intestinal microbiome. METHODS: Patients 18-75 years presenting for upper endoscopy were recruited prospectively. Observational study participants completed a lactose intolerance symptom questionnaire and reported lactose intake. Post-bulbar biopsies were obtained to measure lactase activity and assess the small intestinal mucosal microbiome. We compared intestinal lactase between patients with and without lactose intolerance. We assessed associations between lactose intolerance symptoms and lactase and lactose intake. We examined associations of small bowel microbial composition with self-reported lactose intolerance and symptoms. RESULTS: Among 34 patients, 23 (68%) reported lactose intolerance. Those with lactose intolerance had higher total symptom scores, more frequent bowel urgency, and more bowel movements after consuming dairy. The proportion of individuals with abnormal lactase activity did not differ by lactose intolerance status. Median lactase levels were correlated with total lactose intolerance symptom scores (p = 0.038) and frequency of bowel urgency (p = 0.012). Daily lactose intake did not differ between groups. In 19 patients, we observed significant associations of small intestinal microbiome beta diversity with stool consistency after consuming dairy (p = 0.03). CONCLUSIONS: Intestinal lactase is associated with lactose intolerance symptoms and bowel urgency in adults but does not distinguish the clinical phenotype entirely. Studying other contributing factors (microbiota, diet) may further clarify the pathophysiology of lactose intolerance.

Virtual Gastroenterology Fellowship Recruitment During COVID-19 and Its Implications for the Future.

BACKGROUND AND AIMS: Amid the COVID-19 pandemic, medical education organizations endorsed a virtual recruitment format, representing a stark change from traditional in-person interviews. We aimed to identify the attitudes and perceptions of Gastroenterology Fellowship Program Directors (PDs) and applicants regarding the virtual interview experience and the role of virtual interviews (VI) in the future. METHODS: We designed separate surveys targeting PDs and applicants using the Qualtrics software. At the end of the interview season, we e-mailed both survey links to all PDs and requested that they forward the applicant survey to their interviewed candidates. Surveys were voluntary and anonymous. Descriptive statistics were used to analyze the data with results presented as percentages. RESULTS: A total of 29.7% of PDs completed the survey. Compared to traditional interviews, VI were viewed by 46.5% of PDs to be very suboptimal or suboptimal. Yet, 69.1% envisioned a role for VI in the future. A total of 14.2% of applicants completed the survey. Compared to traditional interviews, VI were viewed by 42.3% of applicants to be very suboptimal or suboptimal. However, 61.8% saw a future role for VI. While both applicants and PDs reported that establishing an interpersonal connection was a disadvantage with VI, applicants placed more emphasis on this need for connection (p = 0.001). CONCLUSION: Overall, PDs and applicants report mixed views with regard to VI but anticipate that it may continue to have a future role. VI may augment future recruitment cycles with care taken to not disadvantage applicants, who rely heavily on the interview process to create personal connections with programs.

Optical diagnosis of colorectal polyps using novel blue light imaging classification among trainee endoscopists.

BACKGROUND: Blue light imaging (BLI) has been shown to improve the characterization of colorectal polyps among the endoscopy experts. We aimed to determine if this technology could be taught to endoscopy trainees while maintaining high accuracy and interobserver agreement. METHODS: Twenty-one gastroenterology trainees (fellows) from two academic institutions participated in this prospective study. Each trainee completed a web-based learning comprising four modules: pre-test, didactic videos explaining the BLI Adenoma Serrated International Classification (BASIC), interactive examples, and post-test assessment. The pre- and post-test modules consisted of reviewing video images of colon polyps in high definition white light imaging and BLI and then applying the BASIC classification to determine if the polyps were likely to be adenomatous. Confidence in adenoma identification (rated '1' to '5'), accuracy in polyp (adenoma vs. non-adenoma) identification, and agreement in characterization per BASIC criteria were derived. RESULTS: Trainee accuracy in the adenoma diagnosis improved from 74.7% (pre-test) to 85.4% (post-test) (P < 0.01). There was a trend towards higher accuracy in polyp characterization with subsequent years of training (1st year fellows 77.4%, 2nd year 88.5%, and final year 94.0%) with consistent improvements after the e-learning across years of trainees. Overall, trainees were able to identify adenoma with a high sensitivity of 86.9%, specificity 83.9%, positive predictive value of 84.4%, and negative predictive value of 86.5%. However, their interobserver agreement in adenoma diagnosis was moderate (k = 0.52). CONCLUSION: The novel BLI classification can be easily taught to gastroenterology trainees using an online module and accuracy improves with years of training reaching >90% for colorectal polyp characterization.

Small Intestine Varices in Cirrhosis at a High-Volume Liver Transplant Center: A Retrospective Database Study and Literature Review.

INTRODUCTION: Esophageal varices are a well-characterized sequela of portal hypertension; however, less is known about varices arising in ectopic locations. We aimed to describe bleeding small intestine varices (SIV) in patients with cirrhosis and compare characteristics and outcomes to published case reports. METHODS: We performed an institutional chart review using billing codes and natural language processing between 2008 and 2019. Inclusion criteria were adult patients with cirrhosis and SIV verified by endoscopy, video capsule, or imaging. Patients with noncirrhotic portal hypertension and stomal varices were excluded. We examined demographic and clinical factors, characteristics of SIV, bleeding, intervention, and outcomes in our series and collated data from published cases identified during a literature review. RESULTS: We identified 71 patients with cirrhosis and SIV (18 bled). The literature search yielded 76 cases with bleeding SIV. Our series and published cases were matched for age, sex, liver disease etiology, and SIV location. Length of stay and transfusion requirements were similar. Aggregate initial treatments (number, hemostasis rate) included medical (n = 7, 57%), endoscopic (n = 48, 56%), interventional radiology (n = 31, 77%), and surgery (n = 8, 87%). Hospital and overall mortality rates were higher in our series (22% and 38%) compared with the published cases (5.3% and 18.4%), respectively (P = 0.02 and P = 0.07). DISCUSSION: A quarter of patients with cirrhosis and SIV experience bleeding, with high transfusion requirements, frequent need for secondary interventions, and high mortality. These findings highlight the need for a multidisciplinary approach and second-line therapeutic modalities in the timely management of bleeding SIV in cirrhosis.

Reproductive Characteristics and Pregnancy Outcomes in Hidden Celiac Disease Autoimmunity.

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.

Estimating the Impact of Verification Bias on Celiac Disease Testing.

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.

The role of female endoscopists: are women gastroenterologists better at obtaining biopsies for celiac disease than men?

OBJECTIVES: Celiac disease (CD) is commonly found in women. Given the sex differences in diagnosed patients, we hypothesized sex differences in physicians obtaining biopsies for CD may exist. MATERIALS AND METHODS: We retrospectively reviewed duodenal biopsies for suspected CD excluding pre-existing CD patients. Appropriate biopsy practice was defined as ≥5 specimens per ACG guidelines. RESULTS: We included 125 patients (females, 92). There were 85 properly (68%) biopsied. Presence of a female endoscopist was associated with better adherence to biopsy guidelines (OR, 2.99, 95% CI, 1.19-7.54; p = .02) which remained significant after multivariable adjustment (adjusted OR, 2.7; p = .047). CONCLUSIONS: Physician sex-based differences in biopsy patterns may exist.

Histoplasmosis in Inflammatory Bowel Disease with Tumor Necrosis Factor-Alpha Inhibitors: Safe to Continue Biologics?

BACKGROUND: The advent of tumor necrosis factor-α (TNF-α) inhibitor therapy has transformed inflammatory bowel disease management; however, these medications carry a boxed warning for risk of serious infections, including invasive fungal infections. AIMS: We aimed to study the clinical features, severity, and outcomes of histoplasmosis in patients on TNF-α inhibitors for IBD. METHODS: We performed a retrospective review of IBD patients receiving TNF-α inhibitors who developed histoplasmosis from January 1, 2001, to May 31, 2018. Patients with drug indications other than ulcerative colitis or Crohn's disease were excluded. IBD was diagnosed histologically, radiographically, or endoscopically. RESULTS: We identified 49 patients (median age 44 years; range 19-76) with histoplasmosis on TNF-α inhibitors. Patients with disseminated disease had a median urine antigen of 10.76 ng/mL compared with pulmonary disease alone 0.375 ng/mL (p < 0.001). Charlson Comorbidity Index and urine antigen levels showed a trend toward predicting disease severity (p > 0.05). Median length of stay was 9.5 days. Itraconazole was used for maintenance in all patients. Median follow-up was 4.7 years. Total treatment duration ranged from 3 to 15 months. TNF-α inhibitor therapy was continued in nine and resumed in ten patients after completing antifungals. Three deaths occurred (6%). CONCLUSIONS: Histoplasmosis outcomes were mostly favorable. Many patients were young with few comorbidities; however, those with more comorbidities experienced more severe histoplasmosis. Compared to prior studies, many of these patients resumed or continued biologic therapy. There were no histoplasmosis recurrences after resuming TNF-α inhibitor therapy. Vigilance for disseminated fungal infections in this patient population is essential.

High prevalence of food intolerances among US internet users.

OBJECTIVE: Food intolerances are commonly reported and are predicted to have gastrointestinal health implications. We aimed to quantify the prevalence of food intolerances among US adults and identify culprit foods through a brief web-based survey. DESIGN: We invited participation in an online cross-sectional survey involving a single questionnaire. Data were summarised using percentages or medians and interquartile range. Participant characteristics by self-reported food intolerance were compared using the Wilcoxon rank sum test and Pearson's χ2 test. Adjusted analyses were performed using multivariable logistic regression. SETTING: The survey was internet-based via Amazon's mechanical Turk, a crowdsourcing website for the completion of requester directed tasks. PARTICIPANTS: Adults who were US-based internet users were invited at ages 18-80. RESULTS: We collected 2133 survey responses (ages 18-79 years). The rate of food intolerance was 24·8 % (95 % CI 23·0, 26·6) in US adults. Younger (P < 0·01), female (P = 0·05) and Asian, African American or multiple race individuals (P < 0·01) predominated. Lactose intolerance was most common. Frequency of a non-lactose food intolerance was 18·1 % (95 % CI 16·5, 19·8). When categorised broadly, grains, fruit, lactose, fish, vegetables, alcohol and nuts were most troublesome for individuals in that order. CONCLUSIONS: Self-reported food intolerance is common in US internet users. The effect of food on gastrointestinal symptoms and avoidant behaviours deserves further attention.