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Objective: To characterize the frequency and predictors of follow-up endoscopic biopsy in patients with celiac disease., Background: The utility of routine follow-up biopsy in patients after a diagnosis of celiac disease is uncertain, especially in patients whose symptoms resolve on the gluten-free diet., Patients and Methods: Using the Merative MarketScan U.S. commercial insurance and Medicare databases, we identified 30,737 patients with biopsy-diagnosed celiac disease. We followed them until they had a second duodenal biopsy (our primary outcome) or insurance coverage ended., Results: Among the patients with celiac disease we identified, 5976 (19.4%) underwent a follow-up biopsy. The median time between initial and follow-up biopsies was 16.8 months. Compared with younger patients, those aged 20 years or older had an increased likelihood of undergoing a follow-up biopsy (cumulative incidence rate at 5 y for patients age ≥20 y was 36.0%, 95% CI: 35.0%-37.1% vs 21.9%, 95% CI: 20.5%-23.4% in patients age ≤19 y). Follow-up biopsies occurred less frequently in more recent calendar years. Follow-up biopsy was more common among patients with an Elixhauser Comorbidity Index of 1 (hazard ratio: 1.09; 95% CI: 1.01-1.17) or ≥2 (hazard ratio: 1.28; 95% CI: 1.20-1.37) compared with patients with an index of zero. Among patients who had a follow-up biopsy, 57% had a celiac disease-related symptom recorded in the 30 days before the procedure., Conclusions: Follow-up duodenal biopsy is performed in a substantial minority of U.S. patients with celiac disease. Adult age and increased comorbidity burden were associated with a greater likelihood of follow-up biopsy. Just under half of follow-up biopsies are performed for routine surveillance, in the absence of persistent symptoms., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Coeliac disease (CeD) is a type of enteropathy characterised by an immune-mediated reaction to ingested gluten, resulting in impaired absorption of nutrients and symptoms such as bloating, abdominal cramping and diarrhoea. Currently, the only treatment for CeD is adherence to a gluten-free diet (GFD). The latest draft guidance from the US Food and Drug Administration recommends that dietitians experienced in CeD management evaluate patients during the screening and treatment period of CeD clinical trials to assess adherence to a GFD. However, there are currently no standardised guidelines on dietary assessment of patients with CeD on a GFD and there is a lack of widespread availability of expertise in this field., Methods: Based on the findings of a literature review conducted between April and September 2023, this article provides an overview of key points to consider in the nutritional and dietary assessment of patients with CeD who are following a GFD, with particular focus on the clinical trial setting., Results: Based on a consensus from dietitians and gastroenterologists experienced in treating patients with CeD, we present specific recommendations for registered dietitians who manage patients with CeD. We also describe the development of a simplified tool for assessment of adherence to a GFD, the Gluten-Free Adherence Survey, based on these recommendations., Conclusions: These guidelines cover nutritional and dietary assessment of patients with CeD, physical assessments, intake of oats, environmental considerations and the disease burden., (© 2024 The Author(s). Journal of Human Nutrition and Dietetics published by John Wiley & Sons Ltd on behalf of British Dietetic Association.)

Coeliac disease is an autoimmune disease characterized by small intestinal villus atrophy and inflammation upon exposure to gluten. It has a global prevalence of approximately 1%. Although the gluten-free diet can be an effective treatment, this diet is burdensome with practical difficulties and frequent inadvertent gluten exposure. Moreover, there are a variety of potential complications and comorbidities of coeliac disease that might be related to malabsorption and/or chronic immune activation. Overall, individuals with coeliac disease have increased mortality compared with the general population, underscoring the severity of this common disease. Comorbidities and complications that have been associated with coeliac disease include poor growth, reproductive complications, kidney and liver diseases, respiratory disease (such as pneumonia) and infections (including sepsis). Furthermore, coeliac disease has been linked to other autoimmune disease and psychiatric disease, as well as certain cancers. Data suggest that mucosal healing on a gluten-free diet might protect against some, but not all, of these complications. In this Review, we present absolute and relative risks of coeliac-associated disorders. We discuss underlying mechanisms, the role of the gluten-free diet and mucosal healing, as well as implications for follow-up and non-dietary treatment of coeliac disease., Competing Interests: Competing interests: J.F.L. has coordinated an unrelated study on behalf of the Swedish Inflammatory Bowel Disease quality register (SWIBREG). That study received funding from the Janssen Corporation. J.F.L. has also received financial support from Merck Sharp & Dohme to develop a paper reviewing national healthcare registers in China. J.F.L. also has a research collaboration on coeliac disease with Takeda. D.A.L. receives a salary as an employee of Takeda Pharmaceuticals., (© 2025. Springer Nature Limited.)

Identifying which patients should undergo serologic screening for celiac disease (CD) may help diagnose patients who otherwise often experience diagnostic delays or remain undiagnosed. Using anonymized outpatient data from the electronic medical records of Maccabi Healthcare Services, we developed and evaluated five machine learning models to classify patients as at-risk for CD autoimmunity prior to first documented diagnosis or positive serum tissue transglutaminase (tTG-IgA). A train set of highly seropositive (tTG-IgA > 10X ULN) cases (n = 677) with likely CD and controls (n = 176,293) with no evidence of CD autoimmunity was used for model development. Input features included demographic information and commonly available laboratory results. The models were then evaluated for discriminative ability as measured by AUC on a distinct set of highly seropositive cases (n = 153) and controls (n = 41,087). The highest performing model was XGBoost (AUC = 0.86), followed by logistic regression (AUC = 0.85), random forest (AUC = 0.83), multilayer perceptron (AUC = 0.80) and decision tree (AUC = 0.77). Contributing features for the XGBoost model for classifying a patient as at-risk for undiagnosed CD autoimmunity included signs of anemia, transaminitis and decreased high-density lipoprotein. This model's ability to distinguish cases of incident CD autoimmunity from controls shows promise as a potential clinical tool to identify patients with increased risk of having undiagnosed celiac disease in the community, for serologic screening., Competing Interests: Declarations. Competing interests: Michael Dreyfuss, Benjamin Getz, Or Ramni, Daniel Underberger, Shlomit Steinberg-Koch, Yonathan Jenudi are paid employees of Predicta Med. Tahel Ilan Ber is a former employee of Predicta Med. Yehuda Shoenfeld owns options in the Predicta Med. Kahn Sagol Maccabi Research and Innovation Centre (KSM) is under a commercial agreement with Predicta Med; Sivan Gazit, Tal Patalon, Gabriel Chodick and Amir Ben-Tov are employed by KSM. Benjamin Lebwohl has no conflicts of interest. Ethics approval: The Maccabi Helsinki Committee provided ethical approval for this study including a full waiver on informed consent (approval #0052-20-MHS)., (© 2024. The Author(s).)

Introduction: Celiac disease (CeD) is increasingly diagnosed in older adults, though few studies have explored complications in this group. As frailty confers increased risk for adverse events, we aimed to explore frailty in older adults with CeD., Methods: In a nationwide Swedish cohort, we identified adults ≥60 years with incident CeD between 2004 and 2017 which we matched to population-based controls without CeD by age, sex, county, and calendar-period. Baseline frailty within 3 years before CeD diagnosis or index date was assessed using the Hospital Frailty Risk Score. Among those without baseline frailty, we used conditional logistic regression to estimate odds ratios and 95% confidence intervals of future frailty at 5 years comparing CeD with controls. Logistic regression was used to evaluate the association between persistent villous atrophy vs mucosal healing and frailty in patients with CeD., Results: A total of 4,646 older adults with CeD were matched to 21,944 non-CeD individuals. Baseline frailty was increased in patients with CeD (54.4%) compared with controls (29.7%, P < 0.001), which existed across all frailty categories: low-risk (43.4% vs 23.8%), intermediate-risk (10.3% vs 5.4%), and high-risk (0.8% vs 0.6%). Among those without baseline frailty, patients with CeD had a 61% increased risk of overall frailty at 5 years (95% confidence interval 1.46-1.78). Mucosal healing in CeD individuals on follow-up biopsy did not protect against future frailty., Discussion: Older adults with CeD were significantly more likely to become frail than matched comparators. This analysis reveals the increased vulnerability that older patients with CeD are likely to experience., (Copyright © 2024 by The American College of Gastroenterology.)

Background: Most people maintaining a gluten-free diet (GFD) do not have celiac disease (CD). Comorbidities and associated conditions in this population are largely unknown., Aims: This study identified demographics, dietary patterns, and diagnoses for patients prescribed a GFD during hospitalization and compared patients with CD to those without CD., Methods: We performed a retrospective cross-sectional study for hospital admissions with a GFD between Jan 1, 2010 and June 30, 2022, while excluding patients missing demographic data (n = 113). We compared patients with and without a CD diagnosis, including multivariable logistic regression to identify characteristics independently associated with a CD diagnosis., Results: We analyzed 1527 hospitalized patients of all ages. A minority (n = 467, 30.6%) carried a CD diagnosis. Age, sex, body mass index, and Medicare/Medicaid enrollment and additional diagnoses associated with a GFD (e.g., IBS) were not significantly different. The CD cohort was more predominantly white (66.6% vs 58.4%, p = 0.007) and non-Hispanic (62.5% vs. 52.7%, p = 0.001). While hospitalized, patients with CD had fewer additional dietary restrictions (mean 0.33 vs 0.56, p < 0.001) and more frequent micronutrient supplementation (26.6% vs 21.4%, p = 0.03). CD was independently associated with malnutrition (OR 1.86, 95% CI 1.31-2.65) and inversely associated with a vegetarian diet (OR 0.35, 95% CI 0.15-0.81), reduced lactose diet (OR 0.25, 95% CI 0.13-0.50), and Hispanic ethnicity (OR 0.56, 95% CI 0.35-0.90) while controlling for other covariates., Discussion: Two-thirds of hospitalized patients receiving a GFD do not have a diagnosis of CD. Among GFD inpatients, CD is associated with fewer dietary restrictions and independently associated with malnutrition., Competing Interests: Declarations Conflict of interest No conflicts of interest and nothing to declare., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: This review highlights recent research in the field of celiac disease., Recent Findings: Epidemiological studies continue to identify celiac disease-associated diseases such as inflammatory arthritis, irritable bowel syndrome, and cardiovascular disease. Recently published consensus guidelines provide recommendations for the long-term management and monitoring of patients with celiac disease. There are multiple pharmaceutical therapies for celiac disease under investigation, and recent phase I and phase II trials are reviewed here. Finally, a recent trial of patients with nonceliac gluten sensitivity demonstrates a significant nocebo effect in this condition., Summary: Recent advances in celiac disease include the development of new clinical guidelines as well as promising new therapeutics. Continued high-quality research is needed to improve the outcomes of patients with celiac disease and nonceliac enteropathies., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The only treatment for Celiac Disease (CeD), which affects about 1% of the population, is a gluten-free diet (GFD). Studies have indicated an association between the GFD, a diminished quality of life (QOL), and maladaptive eating patterns. This study aims to explore food avoidance behaviors in adults with CeD., Methods: This cross-sectional study assessed 50 adults with biopsy-confirmed CeD who completed validated surveys evaluating demographics, psychological factors, QOL, eating pathology, and food avoidance., Results: Overall CDQOL scores were good (mean: 62.7 out of 100). However, 58.0% of the participants self-elected to avoid one or more additional foods without diagnosed allergies or intolerances. Those avoiding one or more other foods had lower QOL scores (57.4 (23.2) vs. 70.2 (15.9)) compared to those only avoiding gluten ( p = 0.034). The mean depression score (CESD) for the group avoiding foods beyond gluten was in the depressive range, unlike those avoiding only gluten (16.0 (4.9) vs. 13.6 (4.0), p = 0.078), with 77% of those avoiding more than gluten scoring above the CESD cut-off point of 15, indicating clinical depression., Conclusions: Over half of participants (58%) reported avoiding additional foods beyond the GFD, a behavior associated with decreased QOL and increased depression.

Celiac disease (CeD) is a common autoimmune condition, with a prevalence of ~1%. Currently, a gluten-free diet (GFD) is the only treatment option. Due to fortification rules excluding gluten-free products in the United States of America (U.S.A.), understanding the nutritional adequacy of a GFD is important for promoting optimal health among those with CeD. Cross-sectional examination of multiple 24 h dietary recalls from a study sample of 50 adults and 30 teens with CeD was used to determine nutritional adequacy and excesses according to U.S.A. recommendations. The results were compared with those of 15,777 adults and 2296 teens from a nationally representative sample not reporting CeD, the National Health and Nutrition Examination Survey (NHANES) 2009-2014. Compared with NHANES, our study population was more at risk of low folate and carbohydrate (adults) consumption, and of excessive niacin and vitamin A (teens), as well as saturated and total fat consumption (adults). Overall, though, compared with NHANES, our study participants had similar nutrient concerns but fewer nutritional imbalances, with some notable exceptions. In addition to maintaining a GFD, individuals with CeD should be counseled to maintain a balanced diet and to pay attention to nutrient-dense foods. Special attention should be given to teens in providing dietary counseling to potentially mitigate the risk of future morbidity.

Aims/hypothesis: While the association between coeliac disease and type 1 diabetes is well documented, the association of coeliac disease with type 2 diabetes risk remains undetermined. We conducted a nationwide cohort and Mendelian randomisation analysis to investigate this link., Methods: This nationwide matched cohort used data from the Swedish ESPRESSO cohort including 46,150 individuals with coeliac disease and 219,763 matched individuals in the comparator group selected from the general population, followed up from 1969 to 2021. Data from 9053 individuals with coeliac disease who underwent a second biopsy were used to examine the association between persistent villous atrophy and type 2 diabetes. Multivariable Cox regression was employed to estimate the associations. In Mendelian randomisation analysis, 37 independent genetic variants associated with clinically diagnosed coeliac disease at p<5×10 -8 were used to proxy genetic liability to coeliac disease. Summary-level data for type 2 diabetes were obtained from the DIAGRAM consortium (80,154 cases) and the FinnGen study (42,593 cases)., Results: Over a median 15.7 years' follow-up, there were 6132 (13.3%) and 30,138 (13.7%) incident cases of type 2 diabetes in people with coeliac disease and comparator individuals, respectively. Those with coeliac disease were not at increased risk of incident type 2 diabetes with an HR of 1.00 (95% CI 0.97, 1.03) compared with comparator individuals. Persistent villous atrophy was not associated with an increased risk of type 2 diabetes compared with mucosal healing among participants with coeliac disease (HR 1.02, 95% CI 0.90, 1.16). Genetic liability to coeliac disease was not associated with type 2 diabetes in DIAGRAM (OR 1.01, 95% CI 0.99, 1.03) or in FinnGen (OR 1.01, 95% CI 0.99-1.04)., Conclusions/interpretation: Coeliac disease was not associated with type 2 diabetes risk., (© 2024. The Author(s).)

Background: Patients on a gluten-free diet (GFD) whose celiac disease (CD) status is unknown may undergo gluten challenge (GC) to clarify their diagnosis. Though this is an established diagnostic practice, the proportion of patients undergoing GC who are diagnosed with CD is unknown., Aims: We aimed to analyze which factors were predictive of having CD in a cohort of patients who underwent GC followed by upper endoscopy with duodenal biopsy., Methods: We identified adult patients at a CD referral center who had been on a GFD and then underwent GC to determine a diagnosis of CD during the years spanning 2006 to 2020. We compared those patients found to have CD (defined as villus atrophy/Marsh 3) on duodenal biopsy with those who did not, using the chi square and Fischer exact tests., Results: We identified 206 patients who underwent GC. Of these 206, 30 (14%) were diagnosed with CD based on post-GC duodenal biopsy. 176 of the 206 (85%) patients reported various gastrointestinal symptoms, including bloating (39%), though these were more common in those without CD (any GI symptoms: 89% vs 67%, p 0.004; bloating: 43% vs 20%, p 0.019). Serology values, when normalized, including pre- and post-challenge TTG IgA (37% vs 1.7%, p 0.001; 23% versus 2.3%, p 0.001), DGP IgG and IgA (57% vs 2.8%, p 0.001; 37% vs 6.2%, p 0.001) were higher in the group of patients with CD., Conclusion: Among patients undergoing GC for diagnostic purposes, only 14% had evidence of villus atrophy corresponding with CD on duodenal biopsy. The presence of any elevated pre-challenge serology was associated with CD. Bloating in combination with low serologies may help risk stratify patients as being less likely to have CD upon GC., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background & Aims: The aim of this study was to determine the risk of irritable bowel syndrome (IBS) diagnosis in patients with celiac disease (CD) compared with general population comparators., Methods: Using Swedish histopathology and register-based data, we identified 27,262 patients with CD diagnosed in 2002-2017 and 132,922 age- and sex-matched general population comparators. Diagnoses of IBS were obtained from nationwide inpatient and non-primary outpatient records. Cox regression estimated hazard ratios (aHRs) for IBS adjusted for education level and Charlson Comorbidity Index. To reduce potential surveillance bias our analyses considered incident IBS diagnosis ≥1 year after CD diagnosis. Using conditional logistic regression, secondary analyses were calculated to estimate odds ratios (ORs) for IBS diagnosis ≥1 year before CD diagnosis., Results: During an average of 11.1 years of follow-up, 732 celiac patients (2.7%) were diagnosed with IBS vs 1131 matched general population comparators (0.9%). Overall (≥1-year of follow-up), the aHR for IBS was 3.11 (95% confidence interval [CI], 2.83-3.42), with aHR of 2.00 (95% CI, 1.63-2.45) after ≥10 years of follow-up. Compared with siblings (n = 32,010), celiac patients (n = 19,211) had ≥2-fold risk of later IBS (aHR, 2.42; 95% CI, 2.08-2.82). Compared with celiac patients with mucosal healing, those with persistent villus atrophy on follow-up biopsy were less likely to be diagnosed with IBS (aHR, 0.66; 95% CI, 0.46-0.95). CD was also associated with having an earlier IBS diagnosis (OR, 3.62; 95% CI, 3.03-4.34)., Conclusions: In patients with CD, the risk of IBS is increased long before and after diagnosis. Clinicians should be aware of these long-term associations and their implications on patient management., (Copyright © 2024 The Authos. Published by Elsevier Inc. All rights reserved.)

Background: Ultra-short coeliac disease (USCD) is defined as villous atrophy only present in the duodenal bulb (D1) with concurrent positive coeliac serology. We present the first, multicentre, international study of patients with USCD., Methods: Patients with USCD were identified from 10 tertiary hospitals (6 from Europe, 2 from Asia, 1 from North America and 1 from Australasia) and compared with age-matched and sex-matched patients with conventional coeliac disease., Findings: Patients with USCD (n=137, median age 27 years, IQR 21-43 years; 73% female) were younger than those with conventional coeliac disease (27 vs 38 years, respectively, p<0.001). Immunoglobulin A-tissue transglutaminase (IgA-tTG) titres at index gastroscopy were lower in patients with USCD versus conventional coeliac disease (1.8×upper limit of normal (ULN) (IQR 1.1-5.9) vs 12.6×ULN (IQR 3.3-18.3), p<0.001).Patients with USCD had the same number of symptoms overall (median 3 (IQR 2-4) vs 3 (IQR 1-4), p=0.875). Patients with USCD experienced less iron deficiency (41.8% vs 22.4%, p=0.006).Both USCD and conventional coeliac disease had the same intraepithelial lymphocytes immunophenotype staining pattern; positive for CD3 and CD8, but not CD4.At follow-up having commenced a gluten-free diet (GFD) (median of 1181 days IQR: 440-2160 days) both USCD and the age-matched and sex-matched controls experienced a similar reduction in IgA-tTG titres (0.5 ULN (IQR 0.2-1.4) vs 0.7 ULN (IQR 0.2-2.6), p=0.312). 95.7% of patients with USCD reported a clinical improvement in their symptoms., Interpretation: Patients with USCD are younger, have a similar symptomatic burden and benefit from a GFD. This study endorses the recommendation of D1 sampling as part of the endoscopic coeliac disease diagnostic workup., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Predominantly antibody deficiency (PAD) is associated with noninfectious inflammatory gastrointestinal disease. Population estimates of celiac disease (CeD) risk in those with PAD are limited., Objective: To estimate population risk of PAD in individuals with CeD., Methods: We conducted a nationwide case-control study in Swedish individuals who received a diagnosis of CeD between 1997 and 2017 (n = 34,980), matched to population comparators by age, sex, calendar year, and county. The CeD was confirmed through the Epidemiology Strengthened by histopathology Reports in Sweden study, which provided information on biopsy specimens from each of Sweden's pathology departments. PAD was identified using International Classification of Diseases, 10th Revision coding and categorized according to the International Union of Immunologic Societies. Logistic regression was used to calculate adjusted odds ratios (aORs) and 95% CIs., Results: PAD was more prevalent in CeD than in population controls (n = 105 [0.3%] vs n = 57 [0.033%], respectively). This translated to an aOR of 8.23 (95% CI 5.95-11.48). The association was strongest with common variable immunodeficiency (aOR 17.25; 95% CI 6.86-52.40), and slightly lower in other PAD (aOR 8.39; 95% CI 5.79-12.32). The risk of CeD remained increased at least 5 years after diagnosis of PAD (aOR 4.79; 95% CI 2.89-7.97, P-heterogeneity ≤ 0.001)., Conclusion: PAD was associated with an increased risk of CeD. A particularly strong association was seen in those with CVID, although this should be interpreted cautiously given the limited understanding of the mechanisms of histopathologic changes in these patients., Competing Interests: Disclosures Dr Khalili receives consulting fees from Takeda and grant funding from Takeda and Pfizer. Dr Ludvigsson has coordinated an effort on behalf of the Swedish Inflammatory Bowel Disease Quality Register that received funding from Janssen corporation and has received support from MSD/Merck for a manuscript reviewing national healthcare registers in China. Dr Farmer has received support from Pharming, Bristol-Myers Squibb, and Pfizer. Dr DiGiacomo has recieved support from Pfizer. These relationships have no direct relation to this work. Dr Roelstrate, Dr Green, Dr Lebwohl, and Dr Hammarstrom have no conflicts of interest to report., (Copyright © 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Purpose: Public health is a necessary focus of modern medical education. However, while numerous studies demonstrate benefits of public health education during medical school among self-selected students (i.e., those interested in public health), there are few educational models shown to be effective across the general medical student population. This study examined the effect of a multiyear, case-based, longitudinal online public health curriculum required for all medical students at an urban, research-focused U.S. medical school., Method: The authors created 11 short public health modules to supplement a year-long, organ-based preclerkship course at Columbia University Vagelos College of Physicians and Surgeons. Beginning in 2020, all students were required to complete these modules, with repeated surveys to assess changes in attitudes and knowledge of public health over time. The authors compared responses for these domains before and after each module, across multiple time points throughout the year, and cross-sectionally to a 2019 cohort of students who were not provided the modules., Results: Across 3 cohorts, 405 of 420 (96.4%) students provided responses and were included in subsequent analyses. After completing the modules, students reported perceiving a greater importance of public health to nearly every medical specialty ( P < .001), more positive attitudes toward public health broadly ( P < .001), and increased knowledge of public health content ( P < .001). These findings were consistent across longitudinal analysis of students throughout the year-long course and when compared to the cohort who did not complete the modules., Conclusions: Case-based, interactive, and longitudinal public health content can be effectively integrated into the required undergraduate medical education curriculum to improve all medical students' knowledge and perceptions of public health. Incorporating evidence-based public health education into medical training may help future physicians to better address the needs of the communities and populations in which they practice., (Copyright © 2024 the Association of American Medical Colleges.)

The accumulating data regarding a non-biopsy diagnosis of celiac disease has led to its adoption in certain scenarios, although debate on whether and when to use non-biopsy criteria in clinical practice is ongoing. Despite the growing popularity and evidence basis for a biopsy-free approach to diagnosis in the context of highly elevated serologies, there will continue to be a role for a biopsy in some groups. This review summarizes the current evidence supporting a non-biopsy approach and arguments supporting continued reliance on biopsy, and focuses on opportunities to improve both approaches., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Celiac disease (CeD) is associated with several immune-mediated disorders, but it is unclear whether it is associated with eosinophilic esophagitis (EoE)., Objective: We sought to examine the risk of EoE in patients with biopsy-verified CeD compared with matched controls and siblings., Methods: Using nationwide population-based histopathology data, we identified 27,338 patients with CeD diagnosed in the period 2002 to 2017 in Sweden. Patients with CeD were age- and sex-matched with up to 5 reference individuals (n = 134,987) from the general population. Cox Regression was used to estimate hazard ratios (HRs) for developing biopsy-verified EoE. In a secondary analysis, we used unaffected siblings of patients with CeD as comparators to adjust for intrafamilial confounding., Results: The median age at CeD diagnosis was 27 years, and 63.3% were female patients. During a median follow-up of 8.1 years, 17 patients with CeD and 13 matched reference individuals were diagnosed with EoE. This corresponded to incidence rates of 0.08 versus 0.01 per 1000 person-years, respectively, and an adjusted HR for EoE of 6.65 (95% CI, 3.26-13.81). Compared with their siblings without CeD, patients with CeD were however at a no increased risk of EoE (HR, 1.39; 95% CI, 0.55-3.51)., Conclusions: In this study, individuals with CeD were at a 6.6-fold increased risk of later EoE compared with the general population. This association might be explained by an altered health-seeking behavior or through shared genetic or early environmental factors because the excess risk disappeared in sibling analyses., Competing Interests: This study was supported by grants from Örebro County Council (avtal om läkarutbildning och forskning [ALF]). A.U. is supported by the Consortium of Eosinophilic Gastrointestinal Disease Researchers. Disclosure of potential conflict of interest: A. Uchida consults for Sanofi-Regeneron and AstraZeneca. J. F. Ludvigsson coordinates a study on behalf of the Swedish Inflammatory Bowel Disease Register (SWIBREG), which has received funding from Janssen Corporation; has also received financial support from Merck Sharp and Dohme (MSD) developing an article reviewing national health care registers in China; and is currently discussing potential research collaboration with Takeda. The rest of the authors declare that they have no relevant conflicts of interest., (© 2024 The Authors.)

Background: The diagnosis of celiac disease (CD) is based on positive IgA autoantibodies to tissue transglutaminase (TTG IgA) and confirmatory histopathology demonstrating duodenal villus atrophy (VA). Diagnostic challenges can occur when VA is found on duodenal biopsies in patients without prior CD serologies., Aims: To characterize the predictors of CD seropositivity in patients with VA on biopsy without prior CD serologies., Methods: We performed a retrospective cohort study of patients found to have duodenal VA on histopathology from 2010 to 2020 who did not have prior CD serologies measured and who had them checked after their biopsy. Patients with known or suspected CD prior to their duodenal biopsy were excluded., Results: Of 162 patients with VA and no prior CD serologies, 50 (31%) subsequently had an elevated TTG IgA consistent with CD. Patients with an elevated TTG IgA were more likely to be non-Hispanic (76% vs. 42%; p < 0.001), white (74% vs. 62%; p = 0.025), and younger (ages 18-39, 26% vs. 12%; p = 0.002) compared to those with a negative TTG IgA. By contrast, these patients were less likely to present in middle adulthood (ages 40-59, 6% vs. 29%; p =  0.002). The most common identified etiologies of seronegative VA were Crohn's disease (13%), seronegative CD (8.9%), H. pylori infection (6.3%), tropical sprue (5.4%), and olmesartan-related enteropathy (3.6%)., Conclusion: Age and ethnicity may be helpful when stratifying the likelihood of CD in the absence of supporting serologies. A majority of patients (69%) diagnosed with VA without prior CD serologies have negative serologies, consistent with seronegative CD or the spectrum of non-celiac enteropathies for which further evaluation is needed., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Coeliac disease (CeD) is an immunological disease triggered by the consumption of gluten contained in food in individuals with a genetic predisposition. Diagnosis is based on the presence of small bowel mucosal atrophy and circulating autoantibodies (anti-type 2 transglutaminase antibodies). After diagnosis, patients follow a strict, life-long gluten-free diet. Although the criteria for diagnosis of this disease are well defined, the monitoring phase has been studied less and there is a lack of specific guidelines for this phase. To develop a set of clinical guidelines for CeD monitoring, we followed the Grading of Recommendations Assessment, Development and Evaluation methodology. Statements and recommendations with the level of evidence were developed and approved by the working group, which comprised gastroenterologists, pathologists, dieticians and biostatisticians. The proposed guidelines, endorsed by the North American and European coeliac disease scientific societies, make recommendations for best practices in monitoring patients with CeD based on the available evidence. The evidence level is low for many topics, suggesting that further research in specific aspects of CeD would be valuable. In conclusion, the present guidelines support clinicians in improving CeD treatment and follow-up and highlight novel issues that should be considered in future studies., (© 2023. Springer Nature Limited.)

Background: Studies on the effect of computer-aided detection (CAD) in a daily clinical screening and surveillance colonoscopy population practice are scarce. The aim of this study was to evaluate a novel CAD system in a screening and surveillance colonoscopy population., Methods: This multicentre, randomised, controlled trial was done in ten hospitals in Europe, the USA, and Israel by 31 endoscopists. Patients referred for non-immunochemical faecal occult blood test (iFOBT) screening or surveillance colonoscopy were included. Patients were randomomly assigned to CAD-assisted colonoscopy or conventional colonoscopy; a subset was further randomly assigned to undergo tandem colonoscopy: CAD followed by conventional colonoscopy or conventional colonoscopy followed by CAD. Primary objectives included adenoma per colonoscopy (APC) and adenoma per extraction (APE). Secondary objectives included adenoma miss rate (AMR) in the tandem colonoscopies. The study was registered at ClinicalTrials.gov, NCT04640792., Findings: A total of 916 patients were included in the modified intention-to-treat analysis: 449 in the CAD group and 467 in the conventional colonoscopy group. APC was higher with CAD compared with conventional colonoscopy (0·70 vs 0·51, p=0·015; 314 adenomas per 449 colonoscopies vs 238 adenomas per 467 colonoscopies; poisson effect ratio 1·372 [95% CI 1·068-1·769]), while showing non-inferiority of APE compared with conventional colonoscopy (0·59 vs 0·66; p<0·001 for non-inferiority; 314 of 536 extractions vs 238 of 360 extractions). AMR in the 127 (61 with CAD first, 66 with conventional colonoscopy first) patients completing tandem colonoscopy was 19% (11 of 59 detected during the second pass) in the CAD first group and 36% (16 of 45 detected during the second pass) in the conventional colonoscopy first group (p=0·024)., Interpretation: CAD increased adenoma detection in non-iFOBT screening and surveillance colonoscopies and reduced adenoma miss rates compared with conventional colonoscopy, without an increase in the resection of non-adenomatous lesions., Funding: Magentiq Eye., Competing Interests: Declaration of interests HN reports equipment from Magentiq Eye. AAB is a consultant for Boston Scientific Corp. SN is a consultant for Boston Scientific Corp, Olympus, and Neptune Medical. HJ reports consultancy fees from Magentiq Eye, and stock options from Magentiq Eye from activities before the clinical trial. PDS reports research support from Pentax, The eNose company, Lucid Diagnostics, Micro Tech, Motus GI, Magentiq Eye, Norgine, and Endo Tools Therapeutics, and consultancy fees from Motus GI and Magentiq Eye. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background & Aims: Fecal microbiota-based therapies include conventional fecal microbiota transplant and US Food and Drug Administration-approved therapies, fecal microbiota live-jslm and fecal microbiota spores live-brpk. The American Gastroenterological Association (AGA) developed this guideline to provide recommendations on the use of fecal microbiota-based therapies in adults with recurrent Clostridioides difficile infection; severe to fulminant C difficile infection; inflammatory bowel diseases, including pouchitis; and irritable bowel syndrome., Methods: The guideline was developed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis. The guideline panel used the Evidence-to-Decision framework to develop recommendations for the use of fecal microbiota-based therapies in the specified gastrointestinal conditions and provided implementation considerations for clinical practice., Results: The guideline panel made 7 recommendations. In immunocompetent adults with recurrent C difficile infection, the AGA suggests select use of fecal microbiota-based therapies on completion of standard of care antibiotics to prevent recurrence. In mildly or moderately immunocompromised adults with recurrent C difficile infection, the AGA suggests select use of conventional fecal microbiota transplant. In severely immunocompromised adults, the AGA suggests against the use of any fecal microbiota-based therapies to prevent recurrent C difficile. In adults hospitalized with severe or fulminant C difficile not responding to standard of care antibiotics, the AGA suggests select use of conventional fecal microbiota transplant. The AGA suggests against the use of conventional fecal microbiota transplant as treatment for inflammatory bowel diseases or irritable bowel syndrome, except in the context of clinical trials., Conclusions: Fecal microbiota-based therapies are effective therapy to prevent recurrent C difficile in select patients. Conventional fecal microbiota transplant is an adjuvant treatment for select adults hospitalized with severe or fulminant C difficile infection not responding to standard of care antibiotics. Fecal microbiota transplant cannot yet be recommended in other gastrointestinal conditions., (Copyright © 2024. Published by Elsevier Inc.)

Background: Coeliac disease (CeD) has been associated with a broad range of diseases in observational data; however, whether these associations are causal remains undetermined. We conducted a phenome-wide Mendelian randomization analysis (MR-PheWAS) to investigate the comorbidities of CeD., Methods: Single nucleotide polymorphisms (SNPs) associated with CeD at the genome-wide significance threshold and without linkage disequilibrium (R 2 <0.001) were selected from a genome-wide association study including 12,041 CeD cases as the instrumental variables. We first constructed a polygenic risk score for CeD and estimated its associations with 1060 unique clinical outcomes in the UK Biobank study (N = 385,917). We then used two-sample MR analysis to replicate the identified associations using data from the FinnGen study (N = 377,277). We performed a secondary analysis using a genetic instrument without extended MHC gene SNPs., Findings: Genetic liability to CeD was associated with 68 clinical outcomes in the UK Biobank, and 38 of the associations were replicated in the FinnGen study. Genetic liability to CeD was associated with a higher risk of several autoimmune diseases (type 1 diabetes and its complications, Graves' disease, Sjögren syndrome, chronic hepatitis, systemic and cutaneous lupus erythematosus, and sarcoidosis), non-Hodgkin's lymphoma, and osteoporosis and a lower risk of prostate diseases. The associations for type 1 diabetes and non-Hodgkin's lymphoma attenuated when excluding SNPs in the MHC region, indicating shared genetic aetiology., Interpretation: This study uncovers multiple clinical outcomes associated with genetic liability to CeD, which suggests the necessity of comorbidity monitoring among this population., Funding: This project was funded by Karolinska Institutet and the Swedish Research Council., Competing Interests: Declaration of interests Dr. Leffler is an employee of Takeda. Dr. Ludvigsson has coordinated an unrelated study for the Swedish IBD quality register (SWIBREG). That study received funding from Janssen Corporation. Dr. Ludvigsson has also received financial support from MSD, developing a paper reviewing national healthcare registers in China. Dr. Ludvigsson has an ongoing research collaboration with Takeda. The other authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: Celiac disease (CeD) has been linked to an increased risk of other autoimmune diseases, yet the impact of delayed CeD diagnosis on risk of developing additional autoimmune diseases remains uncertain. We investigated this through a nationwide matched case-control study., Methods: Using the ESPRESSO cohort with histophatology data from Sweden's 28 pathology departments, we assessed 46,575 biopsy-confirmed CeD cases from 1964 to 2017. We extracted 225,295 matched controls without histopathology information from the Swedish Total Population Register. Autoimmune disease was defined through diagnostic codes in the National Patient Register. Through conditional logistic regression we estimated odds ratio (OR) of autoimmune disease up until CeD diagnosis/matching date comparing CeD cases to controls across different age strata., Results: A total of 3059 (6.6 %) CeD patients and 4076 (1.8 %) controls had earlier autoimmune disease. The overall OR for autoimmune disease in CeD was 3.50 (95%CI 3.32-3.70). The risk of autoimmune disease did not escalate with increasing age at CeD diagnosis. Compared with controls, the OR of autoimmune disease in CeD patients was 7.70 (95%CI 4.71-12.57) in those diagnosed with CeD in 0-4 years, 19.02 (95%CI 13.80-26.23) in 5-9 years, 6.18 (95%CI 5.14-7.44) in 10-14 years, 4.80 (95%CI 3.97-5.79) in 15-19 years, 4.24 (95%CI 3.55-5.07) in 20-29 years, 4.65 (95%CI 3.93-5.51) in 30-39 years, 3.67 (95%CI 3.30-4.09) in 40-59 years, and 1.67 (95%CI 1.50-1.85) in ≥60 years., Conclusions: This study revealed an increased risk of autoimmune disease among CeD patients compared with controls. However, older age at CeD diagnosis did not seem to escalate the risk of autoimmune diseases., Competing Interests: Declaration of competing interest Dr. Leffler is an employee of Takeda. Dr. Ludvigsson has coordinated an unrelated study for the Swedish IBD quality register (SWIBREG). That study received funding from Janssen Corporation. Dr. Ludvigsson has also received financial support from MSD, developing a paper reviewing national healthcare registers in China. Dr. Ludvigsson has an ongoing research collaboration with Takeda. The other authors report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: We evaluated the associations between celiac disease (CD) prevalence and regional sociodemographic variables in the United States., Methods: The outcome was CD relative prevalence, defined as number of patients with CD among those in a Medicare registry per 3-digit ZIP code. Linear regression models assessed associations between relative prevalence of CD and sociodemographic variables., Results: CD relative prevalence was positively correlated with median income, urban area, and proximity to a CD specialty center and negatively correlated with Black race, Latino/Hispanic ethnicity, and median social deprivation index score ( P < 0.01, all)., Discussion: CD relative prevalence is associated with indicators of economic advantage., (Copyright © 2023 by The American College of Gastroenterology.)

Background & Aims: There is a need to develop safe and effective pharmacologic options for the treatment of celiac disease (CeD); however, consensus on the appropriate design and configuration of randomized controlled trials (RCTs) in this population is lacking., Methods: A 2-round modified Research and Development/University of California Los Angeles Appropriateness Method study was conducted. Eighteen gastroenterologists (adult and pediatric) and gastrointestinal pathologists voted on statements pertaining to the configuration of CeD RCTs, inclusion and exclusion criteria, gluten challenge, and trial outcomes. Two RCT designs were considered, representing the following distinct clinical scenarios for which pharmacotherapy may be used: trials incorporating a gluten challenge to simulate exposure; and trials evaluating reversal of histologic changes, despite attempted adherence to a gluten-free diet. Each statement was rated as appropriate, uncertain, or inappropriate, using a 9-point Likert scale., Results: For trials evaluating prevention of relapse after gluten challenge, participants adherent to a gluten-free diet for 12 months or more with normal or near-normal-sized villi should be enrolled. Gluten challenge should be FODMAPS (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) free, and efficacy evaluated using histology with a secondary patient-reported outcome measure. For trials evaluating reversal of villus atrophy, the panel voted it appropriate to enroll participants with a baseline villus height to crypt depth ratio ≤2 and measure efficacy using a primary histologic end point. Guidance for measuring histologic, endoscopic, and patient-reported outcomes in adult and pediatric patients with CeD are provided, along with recommendations regarding the merits and limitations of different end points., Conclusions: We developed standardized recommendations for clinical trial design, eligibility criteria, outcome measures, gluten challenge, and disease evaluations for RCTs in patients with CeD., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Abstract: Generations of medical educators have recommended including public and population health (PPH) content in the training of U.S. physicians. The COVID-19 pandemic, structural racism, epidemic gun violence, and the existential threats caused by climate change are currently unsubtle reminders of the essential nature of PPH in medical education and practice. To assess the state of PPH content in medical education, the authors reviewed relevant guidance, including policies, standards, and recommendations from national bodies that represent and oversee medical education for physicians with MD degrees.Findings confirm that guidance across the medical education continuum, from premedical education to continuing professional development, increasingly includes PPH elements that vary in specificity and breadth. Graduate medical education policies present the most comprehensive approach in both primary care and subspecialty fields. Behavioral, quantitative, social, and systems sciences are represented, although not uniformly, in guidance for every phase of training. Quantitative PPH skills are frequently presented in the context of research, but not in relation to the development of population health perspectives (e.g., evidence-based medicine, quality improvement, policy development). The interdependence between governmental public health and medical practice, environmental health, and the impact of structural racism and other systems of oppression on health are urgent concerns, yet are not consistently or explicitly included in curricular guidance. To prepare physicians to meet the health needs of patients and communities, educators should identify and address gaps and inconsistencies in PPH curricula and related guidance.Re-examinations of public health and health care systems in the wake of the COVID-19 pandemic support the importance of PPH in physician training and practice, as physicians can help to bridge clinical and public health systems. This review provides an inventory of existing guidance (presented in the appendices) to assist educators in establishing PPH as an essential foundation of physician training and practice., (Copyright © 2023 the Association of American Medical Colleges.)

Purpose: Proton pump inhibitors (PPIs) are among the most commonly used drugs in the United States (U.S.). We aimed to determine the trends in use of PPIs among adults in the U.S. from 1999 through 2018, hypothesizing the trend would follow an inverted U-shaped curve, with a decline in recent years due to safety concerns., Methods: Temporal trends in use of prescription PPIs were assessed using the 1999-2018 National Health and Nutrition Examination Survey (NHANES), a nationally representative cross-sectional survey of non-institutionalized U.S. civilians. Use of PPIs was defined as any use during the month preceding the survey. Descriptive statistics were produced and trends in PPI use were examined, stratified by sex, age, race, body mass index (BMI), and poverty level., Results: Use of prescription PPIs increased from 4.1% of U.S. adults in 1999-2000 to 8.6% in 2017-2018 (p for trend <0.01). All of the increase was observed during the first half of the study period (4.6% increase from 1999 to 2008 vs. 0.5% decrease from 2009 to 2018) and almost all of it was among those aged 55 or more (8.6% increase among those aged ≥ 55 compared to 1.2% increase among those aged < 55, p for interaction based on age <0.01)., Conclusions: Use of prescription PPIs increased from 1999 to 2008 and then plateaued through 2018. This rise was driven by increased usage among older NHANES respondents., (© 2023 John Wiley & Sons Ltd.)

Background: Data on COVID-19 vaccine effectiveness among patients with coeliac disease are currently lacking because patients with immune conditions were excluded from clinical trials. We used our coeliac disease autoimmunity (CDA) cohort to explore the effectiveness of the BNT162b2 mRNA COVID-19 vaccine in preventing SARS-CoV-2 infection among patients with CDA., Methods: This retrospective cohort study included patients with positive autoantibodies against tissue transglutaminase (tTG-IgA). In the primary analysis, the cohort included CDA patients who received two vaccine doses against COVID-19 and matched patients in a 1:3 ratio. Patients were divided into subgroups based on their positive tTG-IgA level at diagnosis and their current serology status., Results: The cohort included 5381 vaccinated patients with CDA and 14,939 matched vaccinated patients. The risk for breakthrough SARS-CoV-2 infection evaluated with Kaplan-Meier survival analysis via log-rank tests was similar between groups ( p = 0.71). In a Cox regression survival analysis, the hazard ratio for breakthrough infection among patients with CDA compared to matched patients was 0.91 (95% confidence interval = 0.77-1.09)., Conclusions: COVID-19 vaccination is effective in patients with coeliac disease autoimmunity. Vaccine effectiveness was comparable to the reference population.

Recent guidelines recommend screening for patients with chronic gastroesophageal reflux disease who have three or more additional risk factors for Barrett's esophagus (BE). Failure to screen high-risk individuals represents a missed opportunity in esophageal adenocarcinoma prevention and early detection. We aimed to determine the frequency of upper endoscopy and prevalence of BE and esophageal cancer in a cohort of United States veterans who possessed four or more risk factors for BE. All patients at VA New York Harbor Healthcare System with at least four risk factors for BE between 2012 and 2017 were identified. Procedure records were reviewed for upper endoscopies performed between January 2012 and December 2019. Multivariable logistic regression was used to determine risk factors associated with undergoing endoscopy and factors associated with BE and esophageal cancer. 4505 patients with at least four risk factors for BE were included. 828 patients (18.4%) underwent upper endoscopy, of which 42 (5.1%) were diagnosed with BE and 11 (1.3%) with esophageal cancer (10 adenocarcinoma; 1 squamous cell carcinoma). Among individuals who underwent upper endoscopy, risk factors associated with undergoing endoscopy included obesity (OR, 1.79; 95% CI, 1.41-2.30; P < 0.001) and chronic reflux (OR, 3.86; 95% CI, 3.04-4.90; P < 0.001). There were no individual risk factors associated with BE or BE/esophageal cancer. In this retrospective analysis of patients with 4 or more risk factors for BE, fewer than one-fifth of patients underwent upper endoscopy, supporting the need for efforts aimed at improving BE screening rates., (Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus 2023.)

Background: Coeliac disease (CeD), a common autoimmune condition, requires strict adherence to a gluten-free diet (GFD). Adherence to the GFD has been associated with quality of life (QOL). However, there may be other diet-related concerns, such as overall diet patterns, including diet quality or ultra-processed food (UPF) consumption, possibly associated with QOL among people with CeD following a GFD that have not been examined., Methods: Diet quality was determined based on 24-h diet recalls of a cross-sectional prospectively recruited sample of 80 participants (50 adults and 30 teens) with biopsy-confirmed CeD ('Study Sample') using the Healthy Eating Index and Alternate Mediterranean Diet score. The amount of UPF consumed was assessed using Nova, a food processing classification system. QOL was measured using Celiac Disease-Specific Quality of Life (CDQOL) and Celiac Disease Pediatric-Specific Quality of Life (CDPQOL). The Study Sample's diet patterns were compared with National Health and Nutrition Examination Survey (NHANES) groups (25 adults reporting prior CeD and GFD; 51 adults with new CeD and no GFD; 15,777 adults and 2296 teens without CeD). The relationship of the Study Sample's diet patterns with CDQOL/CDPQOL was assessed using analysis of covariance., Results: The Study Sample's diet patterns were suboptimal but generally favourable compared with all NHANES groups. Compared to Study Adults with the highest tertile of UPF, those with the lowest tertile had significantly higher CDQOL (mean: 67.6 vs. 78.3, p < 0.001). Compared to Study Teens with the lowest tertile of AMED, those with the highest tertile had significantly higher CDPQOL (mean: 67.0 vs. 79.9, p < 0.01)., Conclusions: Maintaining high diet quality and minimising UPF may be important for CeD-specific QOL among individuals with CeD maintaining a GFD., (© 2023 The British Dietetic Association Ltd.)

Introduction: Several earlier studies have indicated an increased risk of cardiac birth defects among infants born to mothers with celiac disease (CeD). Through linking nationwide Swedish health care registries, we aimed to investigate maternal CeD and risk of any or cardiac birth defects in their offspring., Methods: We performed a retrospective cohort study of infants born between 2002 and 2016 to women with biopsy-proven CeD (villous atrophy, Marsh III) matched to infants born to nonceliac women from the general population. Conditional logistic regression with odds ratios (OR) and their 95% confidence intervals (CI) was used to determine the association between maternal CeD and birth defects. To minimize the impact of intrafamilial confounding, we also compared infants born to mothers with CeD with infants born to their nonaffected sisters., Results: A total of 6,990 infants were born to mothers with diagnosed CeD compared with 34,643 infants born to reference mothers. Any birth defect was seen in 234 (33 per 1,000 infants) and 1,244 (36/1,000) reference infants corresponding to an OR of 0.93 (95% CI 0.81-1.08). Cardiac birth defects were seen in 113 (16/1,000) vs 569 (16/1,000) infants (OR 0.98, 95% CI 0.80-1.20). Similar OR for any and cardiac birth defects were also seen in sibling comparisons., Discussion: We found no statistically significant risk of any or cardiac birth defects in infants born to mothers with diagnosed CeD compared with the general population and to their nonaffected sisters., (Copyright © 2023 by The American College of Gastroenterology.)

Celiac disease (CD) is an autoimmune disease in which intestinal inflammation is induced by dietary gluten. The means through which gluten-specific CD4 + T cell activation culminates in intraepithelial T cell (T-IEL)-mediated intestinal damage remain unclear. Here, we performed multiplexed single-cell analysis of intestinal and gluten-induced peripheral blood T cells from patients in different CD states and healthy controls. Untreated, active, and potential CD were associated with an enrichment of activated intestinal T cell populations, including CD4 + follicular T helper (T FH ) cells, regulatory T cells (T regs ), and natural CD8 + αβ and γδ T-IELs. Natural CD8 + αβ and γδ T-IELs expressing activating natural killer cell receptors (NKRs) exhibited a distinct TCR repertoire in CD and persisted in patients on a gluten-free diet without intestinal inflammation. Our data further show that NKR-expressing cytotoxic cells, which appear to mediate intestinal damage in CD, arise from a distinct NKR-expressing memory population of T-IELs. After gluten ingestion, both αβ and γδ T cell clones from this memory population of T-IELs circulated systemically along with gluten-specific CD4 + T cells and assumed a cytotoxic and activating NKR-expressing phenotype. Collectively, these findings suggest that cytotoxic T cells in CD are rapidly mobilized in parallel with gluten-specific CD4 + T cells after gluten ingestion.

Background: The only treatment for celiac disease (CeD) is strict lifelong adherence to a gluten-free diet (GFD). In some individuals the demands of a GFD may contribute to maladaptive eating attitudes and behaviors that impair quality of life (QOL). The Celiac Disease Food Attitudes and Behaviors (CD-FAB) is an easily administered and scored 11-item tool querying potentially maladaptive food attitudes and behaviors resulting from beliefs around gluten exposures and food safety., Objectives: To assess the usefulness of the CD-FAB in establishing the presence of maladaptive food attitudes and behaviors among adults with CeD and to explore the relationship between these attitudes and behaviors and other factors including QOL, anxiety, depression, CeD symptoms and personality traits., Methods: The study is a cross-sectional pilot of 50 adults (mean age 29.6 years) with biopsy-proven CeD who followed a GFD for at least one year and had no self-reported eating disorder diagnosis. High scores on the CD-FAB tool suggest higher disordered eating attitudes and beliefs., Results: Compared to lower scores (mean 20.2), higher (worse) CD-FAB scores (mean 54.5) were positively associated with recency of diagnosis, number of CeD-related gastrointestinal symptoms, and the personality trait of neuroticism. Higher CD-FAB scores were statistically and clinically significantly associated with diminished QOL (p < 0.001). The relationship with anxiety and depression was less clear but trended in the expected direction., Conclusion: The CD-FAB may be a useful tool for dietitians who wish to monitor maladaptive food attitudes and behaviors among their CeD patients, especially in the first-year post-diagnosis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The aim of this review is to broadly cover how the COVID-19 pandemic has affected individuals with celiac disease, including perceived risk, risk of contraction or severe infection, considerations regarding vaccination, access to gluten-free food during the pandemic, and possible long-term changes to the practice of celiac disease management spurred by the pandemic. While initially there was increased perceived risk about COVID-19 in the celiac disease population, studies have found that individuals with celiac disease are not at an increased risk of contracting or having a severe course compared to the general population. There is not yet evidence that COVID-19 infection will lead to an increase in celiac disease incidence, though more research on this topic with longer-term follow-up is necessary to make this determination. Limited access to in-person visits led to an increase in telemedicine, which was adopted swiftly by this patient population and may offer improved access in the long term. In summary, individuals with celiac disease do not appear to be at an increased risk of contracting COVID-19 or having a more severe disease course., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2023.)

For patients with celiac disease (CeD), a lifelong gluten-free diet is not a voluntary lifestyle choice-it is a necessity. The key end points in clinical follow-up are symptom resolution, the normalization of weight, prevention of overweight, seroconversion, and negation or minimization of increased long-term morbidity. For the latter, a surrogate endpoint is mucosal healing, which means the normalization of histology to Marsh 0-1. Ideally, celiac follow-up care includes a multidisciplinary approach, effective referral processes, improved access that leverages technological advances, and following guidelines with the identification of measurable quality indicators, ideally informed by evidence-based research. Face-to-face CeD care and telemedicine are considered the standards for this process, although published data are insufficient. Guidelines and statements on diagnosis are readily available. However, data are lacking on optimal clinic visit intervals and outcomes and quality indicators such as improvement of symptoms, function and quality of life, survival and disease control, and how to most effectively use healthcare resources. The results of future research should provide the basis for general recommendations for evidence-based standards of quality of care in CeD.

Beethoven's autopsy findings of cirrhosis may have been due to alcoholism. This condition may have been underemphasized historically, given its stigma and the incongruence with the often heroic portrayal of Beethoven. We therefore aimed to compare how medical experts and biographers writing for a non-medical audience describe his final illness in the context of alcoholism. English-language biographies were identified using a survey of biographies of Beethoven and supplemented by the authors. English-language medical publications were identified by searching for "Beethoven" in the PubMed® MEDLINE database. We included studies that mentioned Beethoven's final illness and death. We recorded statements regarding alcohol consumption, alcoholism, or alcohol use disorder, and the role of alcohol in Beethoven's death. The most commonly cited final illness was liver disease. Alcohol use was more frequently mentioned in biographies, but alcoholism less so. Alcohol use was invoked as a possible cause of final illness more frequently by medical publications., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, ein Teil von Springer Nature.)

Background & Aims: The incidence of biopsy-confirmed celiac disease has increased. However, few studies have explored the incidence of celiac autoimmunity based on positive serology results., Methods: A population-based cohort study assessed testing of tissue transglutaminase antibodies (tTG-IgA) in Alberta from 2012 to 2020. After excluding prevalent cases, incident celiac autoimmunity was defined as the first positive tTG-IgA result between 2015 and 2020. Testing and incidence rates for celiac autoimmunity were calculated per 1000 and 100,000 person-years, respectively. Incidence rate ratios (IRRs) were calculated to identify differences by demographic and regional factors. Average annual percent changes (AAPCs) assessed trends over time., Results: The testing rate of tTG-IgA was 20.2 per 1000 person-years and remained stable from 2012 to 2020 (AAPC, 1.2%; 95% confidence interval [CI], -0.5 to 2.9). Testing was higher in female patients (IRR, 1.66; 95% CI, 1.65-1.66), those living in metropolitan areas (IRR, 1.39; 95% CI, 1.38-1.40), and in areas of lower socioeconomic deprivation (lowest compared to highest IRR, 1.24; 95% CI, 1.23-1.25). Incidence of celiac autoimmunity was 33.8 per 100,000 person-years and increased from 2015 to 2020 (AAPC, 6.2%; 95% CI, 3.1-9.5). Among those with tTG-IgA results ≥10 times the upper limit of normal, the incidence was 12.9 per 100,000 person-years. The incidence of celiac autoimmunity was higher in metropolitan settings (IRR, 1.28; 95% CI, 1.21-1.35) and in the least socioeconomically deprived areas compared to the highest (IRR, 1.22; 95% CI, 1.14-1.32)., Conclusions: Incidence of celiac autoimmunity is high and increasing, despite stable testing rates. Variation in testing patterns may lead to underreporting the incidence of celiac autoimmunity in nonmetropolitan areas and more socioeconomically deprived neighborhoods., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: An association has been reported between celiac disease (CD) and microscopic colitis (MC). However, large, population-based cohort studies are rare., Objective: To systematically examine the association between CD and MC in a large, nationwide cohort., Methods: We conducted a nationwide population-based matched cohort study in Sweden of 45,138 patients with biopsy-verified CD (diagnosed in 1990-2016), 223,149 reference individuals, and 51,449 siblings of CD patients. Data on CD and MC were obtained from all (n = 28) pathology departments in Sweden. Adjusted hazard ratios (aHRs) were calculated using Cox regression., Results: During follow-up, 452 CD patients and 197 reference individuals received an MC diagnosis (86.1 vs. 7.5 per 100,000 person-years). This difference corresponded to an aHR of 11.6 (95% confidence interval [CI] = 9.8-13.8) or eight extra MC cases in 1000 CD patients followed up for 10 years. Although the risk of MC was highest during the first year of follow-up (aHR 35.2; 95% CI = 20.1-61.6), it remained elevated even after 10 years (aHR 8.1; 95% CI = 6.0-10.9). Examining MC subtypes lymphocytic colitis (LC) and collagenous colitis (CC) separately, the aHR was 12.4 (95% CI = 10.0-15.3) for LC and 10.2 (95% CI = 7.7-13.6) for CC. MC was also more common before CD (adjusted odds ratio [aOR] = 52.7; 95% CI = 31.4-88.4). Compared to siblings, risk estimates decreased but remained elevated (CD and later MC: HR = 6.2; CD and earlier MC: aOR = 7.9)., Conclusion: Our study demonstrated a very strong association of MC with CD with an increased risk of future and previous MC in CD patients. The magnitude of the associations underscores the need to consider the concomitance of these diagnoses in cases in which gastrointestinal symptoms persist or recur despite a gluten-free diet or conventional MC treatment. The comparatively lower risk estimates in sibling comparisons suggest that shared genetic and early environmental factors may contribute to the association between CD and MC., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

This guideline presents an update to the 2013 American College of Gastroenterology Guideline on the Diagnosis and Management of Celiac Disease with updated recommendations for the evaluation and management of patients with celiac disease (CD). CD is defined as a permanent immune-mediated response to gluten present in wheat, barley, and rye. CD has a wide spectrum of clinical manifestations that resemble a multisystemic disorder rather than an isolated intestinal disease, and is characterized by small bowel injury and the presence of specific antibodies. Detection of CD-specific antibodies (e.g., tissue transglutaminase) in the serum is very helpful for the initial screening of patients with suspicion of CD. Intestinal biopsy is required in most patients to confirm the diagnosis. A nonbiopsy strategy for the diagnosis of CD in selected children is suggested and discussed in detail. Current treatment for CD requires strict adherence to a gluten-free diet (GFD) and lifelong medical follow-up. Most patients have excellent clinical response to a GFD. Nonresponsive CD is defined by persistent or recurrent symptoms despite being on a GFD. These patients require a systematic workup to rule out specific conditions that may cause persistent or recurrent symptoms, especially unintentional gluten contamination. Refractory CD is a rare cause of nonresponsive CD often associated with poor prognosis., (Copyright © 2022 by The American College of Gastroenterology.)

Introduction: Celiac disease (CD) is associated with many immune-mediated conditions, but a definitive epidemiological association between CD and juvenile idiopathic arthritis (JIA) or rheumatoid arthritis (RA) has not been established. We quantified the risk of JIA and RA among patients with CD using a population-based cohort., Methods: We identified patients diagnosed with biopsy-proven CD between 2004 and 2017 using data from a national histopathology cohort in Sweden. Each patient was matched by age, sex, calendar year, and geographic region to reference individuals in the general population. We calculated the incidence and estimated the relative risk, through Cox proportional hazards models, of JIA in individuals with CD aged <18 and of RA in individuals with CD aged ≥18., Results: We identified 24,014 individuals with CD who were matched to 117,397 reference individuals from the general population. Among individuals aged <18, the incidence rate of JIA was 5.9 per 10,000 person-years in patients with CD and 2.2 per 10,000 person-years in the general population (n events = 40 and 73, respectively; hazard ratio [HR] 2.68, 95% confidence interval 1.82-3.95) over a follow-up of 7.0 years. Among individuals aged ≥ 18, the incidence of RA was 8.4 per 10,000 person-years in CD and 5.1 per 10,000 person-years in matched comparators (n events = 110 and 322, respectively; HR 1.70, 95% confidence interval 1.36-2.12) over a follow-up of 8.8 years., Discussion: Among children with CD, JIA develops nearly 3 times as often as it does in the general population, and among adults with CD, RA occurs nearly 2 times as often. Clinicians caring for patients with CD with joint symptoms should have a low threshold to evaluate for JIA or RA., (Copyright © 2022 by The American College of Gastroenterology.)

Celiac disease (CD) is an autoimmune disorder mediated by an immune response to dietary gluten that affects the small intestine and leads to inflammation, malabsorption, and systemic consequences. 1 The only established therapy is strict adherence to a gluten-free diet. 2,3 Recently there has been growth in the development of novel non-dietary therapies for patients with CD, 4 which are driven by dissatisfaction with the burden of the gluten-free diet. 5,6 ., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background/aims: When seeking a romantic partner, individuals with celiac disease (CD) must navigate challenging social situations. We aimed to investigate dating-related behaviors in adults with CD., Methods: A total of 11,884 affiliates of the Celiac Disease Center at Columbia University were invited to participate in an online survey. Adults (≥ 18 years) with biopsy-diagnosed CD were included. Among the 5,249 who opened the email, 538 fully completed the survey (10.2%). The survey included a CD-specific dating attitudes/behaviors questionnaire, a Social Anxiety Questionnaire (SAQ), a CD-specific quality of life instrument (CD-QOL), and a CD Food Attitudes and Behaviors scale (CD-FAB)., Results: Respondents were primarily female (86.8%) and the plurality (24.4%) was in the 23-35 year age range. 44.3% had dated with CD, and among them, 68.4% reported that CD had a major/moderate impact on their dating life. A major/moderate impact was more commonly reported among females (69.3%, p  < 0.001), 23-35-year-olds (77.7%, p = 0.015), those with a household income < $50 K (81.7%, p = 0.019), and those with a lower CD-QOL score (50.5 vs. 73.4, p = 0.002). While on dates, 39.3% were uncomfortable explaining precautions to waiters, 28.2% engaged in riskier eating behaviors, and 7.5% intentionally consumed gluten. 39.0% of all participants were hesitant to kiss their partner because of CD; females more so than males (41.1% vs. 22.7%, p = 0.005)., Conclusions: The majority of participants felt that CD had a major/moderate impact on their dating life. This impact may result in hesitation toward dating and kissing, decreased QOL, greater social anxiety, and less adaptive eating attitudes and behaviors. CD and the need to adhere to a gluten free diet have a major impact on dating and intimacy., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Differential diagnosis of villous atrophy (VA) without coeliac antibodies in adults includes seronegative coeliac disease (CD) and chronic enteropathies unrelated to gluten, ie. non-coeliac enteropathies (NCEs). There is currently no international consensus on the nomenclature and diagnostic criteria for these enteropathies. In this work, a Delphi process was conducted to address this diagnostic and clinical uncertainty., Design: An international task force of 13 gastroenterologists from six countries was recruited at the 16th International Coeliac Disease Symposium, Paris, 2019. Between September 2019 and July 2021, a Delphi process was conducted through mail surveys to reach a consensus on which conditions to consider in the differential diagnosis of VA with negative coeliac serology and the clinical diagnostic approaches required for these conditions. A 70% agreement threshold was adopted., Results: Chronic enteropathies characterised by VA and negative coeliac serology can be attributed to two main clinical scenarios: forms of CD presenting with negative serology, which also include seronegative CD and CD associated with IgA deficiency, and NCEs, with the latter recognising different underlying aetiologies. A consensus was reached on the diagnostic criteria for NCEs assisting clinicians in differentiating NCEs from seronegative CD. Although in adults seronegative CD is the most common aetiology in patients with VA and negative serology, discriminating between seronegative CD and NCEs is key to avoid unnecessary lifelong gluten-free diet, treat disease-specific morbidity and contrast poor long-term outcomes., Conclusion: This paper describes the Paris consensus on the definitions and diagnostic criteria for seronegative CD and chronic NCEs in adults., Competing Interests: Competing interests: JAM has received study grants from Nexpep/ImmusanT, National Institutes of Health, Immunogenics, Johnson & Johnson, Kanyos/Anakion, Takeda Pharmaceutical, Allakos, Oberkotter, and Cour; consultancy fees from Bionix, UKKO, Dren Bio, Dr. Schär USA, Immunic, Chugai Pharma; holds patents licenced to Evelo Biosciences; and receives royalties from Torax Medical. GM received consultancy fees from Calypso Biotech. DAL: Takeda Pharmaceuticals., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)