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Background Rumination syndrome is a functional gastrointestinal disorder characterized by effortless and repetitive regurgitation of recently ingested food from the stomach to the oral cavity followed by either re-swallowing or spitting. Rumination is thought to occur due to a reversal of the esophagogastric pressure gradient. This is achieved by a coordinated abdominothoracic maneuver consisting of a thoracic suction, crural diaphragm relaxation and an increase in intragastric pressure. Careful history is important in the diagnosis of rumination syndrome; patients often report 'vomiting' or 'reflux' and the diagnosis can therefore be missed. Objective testing is available with high resolution manometry or gastroduodenal manometry. Increase in intra-gastric pressure followed by regurgitation is the most important characteristic to distinguish rumination from other disorders such as gastroesophageal reflux. The mainstay of the treatment of rumination syndrome is behavioral therapy via diaphragmatic breathing in addition to patient education and reassurance. Purpose The purpose of this review was to critically appraise recent key developments in the pathophysiology, diagnosis and therapy for rumination syndrome. A literature search using OVID (Wolters Kluwer Health, New York, NY, USA) to examine the MEDLINE database its inception until May 2016 was performed using the search terms 'rumination syndrome,' 'biofeedback therapy,' and 'regurgitation.' References lists and personal libraries of the authors were used to identify supplemental information. Articles published in English were reviewed in full text. English abstracts were reviewed for all other languages. Priority was given to evidence obtained from randomized controlled trials when possible. [ABSTRACT FROM AUTHOR]

Objectives: The prevalence of celiac disease (CeD) is increasing, yet it is still underdiagnosed, in part because of its heterogeneous presentation. Diagnostic criteria are evolving and management with strict adherence to a gluten-free diet is challenging for many. We aimed to characterize the clinical presentation of CeD among a large multicenter cohort of pediatric patients and to identify factors associated with gluten-free diet adherence., Methods: Patients with CeD aged 0-18 years were recruited from 11 United States health centers. Parents completed surveys about gluten-free diet adherence and patient electronic health records were reviewed. Logistic regression analyses were performed to identify risk factors associated with gluten exposure., Results: Charts were reviewed for 460 children with a median age of 6.4 years. Abdominal pain was reported in 57% of the cohort, but diverse symptoms were identified. Parent surveys were completed for 455 participants. Sixty-five (14%) participants were at high risk for gluten exposure based on parental reports of weekly or daily gluten exposure or eating gluten by choice in the past year. Participants under the age of 5 years had a lower risk of gluten exposure, while participants without repeat serology testing 18 months after initial diagnosis were at higher risk of gluten exposure., Conclusions: In a large, multicenter cohort of pediatric CeD patients, clinical presentation is highly variable, necessitating a high index of suspicion to make a diagnosis. Parent surveys indicate that 14% of patients are at high risk of gluten exposure, with patient age and lack of close follow-up associated with gluten-free diet adherence., (© 2024 The Author(s). Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: Eosinophilic esophagitis (EoE) is often diagnosed in school-age children between 6- and 9-year-old. There is less known about those who are diagnosed with EoE that are younger than 6 years old. The objective of this study is to compare clinical presentation, comorbidities, and outcomes based on age at diagnosis of EoE., Methods: Single-center retrospective chart review of children (<18 years) diagnosed with EoE between 2005 and 2020. We recorded demographics, clinical presentation, family history, past medical history, treatment, and endoscopic findings. Children in this cohort were classified based on age into three age groups: <2 years, 2-<6 years, and 6-<18 years., Results: We identified 256 children with EoE, the mean age (SD) at the time of diagnosis was 9 (5.2) years and 184 (72%) were male. We had 164 (64%) patients with available follow-up esophagogastroduodenoscopies (EGDs) data (495 EGDs in total) of those 99/164 (60%) reached mucosal remission. In the very young children (<2 years) vomiting was the most common presentation, while poor weight gain was seen more in the 2-<6-year group in comparison to the >6-years. Food impaction and abdominal pain were most likely to present in older children 6-18 years. Combination therapy, as opposed to a single therapy, induced remission at a higher frequency in the <6-year group in comparison to the 6-<18-year group (85% vs. 66%)., Conclusion: EoE should be considered in younger children presenting with feeding difficulty and poor weight gain. Combination therapy seems to be more effective in younger children with EoE, but further studies with bigger sample size are needed to study the efficacy of the different combination therapies., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: While guidelines exist for the diagnosis and management of pediatric celiac disease (CeD), current practices in North America are not well-described. This study aimed to explore current practice patterns to identify gaps and direct future clinical, training and research initiatives., Methods: A 23-item survey designed by the Celiac Disease Special Interest Group was distributed electronically to its members. Questions explored four themes: (1) screening and diagnosis pre and post the coronavirus disease (COVID)-19 pandemic, (2) treatment and monitoring, (3) family screening and transition of care, and (4) CeD focused training., Results: The survey response rate was 10.8% (278/2552). Most respondents were from the United States (89.9%, n  = 250) and Canada (8.6%, n  = 24). While endoscopy remained the gold standard, serology-based diagnosis was accepted by 47.5% (132/278). In response to the COVID-19 pandemic, 37.4% of providers changed their diagnostic practice. Barriers to care included: lack of insurance coverage for dietitians, wait times, and lack of CeD focused training. During fellowship 69.1% (192/278) reported no focused CeD training., Conclusion: Survey results revealed practice variation regarding the diagnosis and management of CeD in North America including a substantial proportion accepting non-biopsy, serology-based diagnosis, which increased during the COVID-19 pandemic. Variations in screening, diagnosis, interval surveillance, and family screening were also identified. Dedicated CeD education in pediatric gastroenterology fellowship may be an opportunity for standardizing practice and advancing research. Future North American guidelines should take current care patterns into consideration and develop new initiatives to improve care of children with CeD., Competing Interests: Dr. Jocelyn Silvester has served on advisory boards for Alimentiv, Mozart Therapeutics, Takeda Pharmaceuticals, and Teva Pharmaceuticals. She has served as site‐PI for clinical trials sponsored by Cour Pharmaceuticals and Takeda Pharmaceuticals and has research support from Milky Way Life Sciences. Research reported in this publication was supported by the National Institute Of Diabetes And Digestive And Kidney Diseases of the National Institutes of Health under Award Number K23DK119584. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The remaining authors declare no conflict of interest., (© 2024 The Author(s). JPGN Reports published by Wiley Periodicals LLC on behalf of The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

We have developed an artificial intelligence (AI)-based digital pathology model for the evaluation of histologic features related to eosinophilic esophagitis (EoE). In this study, we evaluated the performance of our AI model in a cohort of pediatric and adult patients for histologic features included in the Eosinophilic Esophagitis Histologic Scoring System (EoEHSS). We collected a total of 203 esophageal biopsy samples from patients with mucosal eosinophilia of any degree (91 adult and 112 pediatric patients) and 10 normal controls from a prospectively maintained database. All cases were assessed by a specialized gastrointestinal (GI) pathologist for features in the EoEHSS at the time of original diagnosis and rescored by a central GI pathologist (R.K.M.). We subsequently analyzed whole-slide image digital slides using a supervised AI model operating in a cloud-based, deep learning AI platform (Aiforia Technologies) for peak eosinophil count (PEC) and several histopathologic features in the EoEHSS. The correlation and interobserver agreement between the AI model and pathologists (Pearson correlation coefficient [r s ] = 0.89 and intraclass correlation coefficient [ICC] = 0.87 vs original pathologist; r s  = 0.91 and ICC = 0.83 vs central pathologist) were similar to the correlation and interobserver agreement between pathologists for PEC (r s  = 0.88 and ICC = 0.91) and broadly similar to those for most other histologic features in the EoEHSS. The AI model also accurately identified PEC of >15 eosinophils/high-power field by the original pathologist (area under the curve [AUC] = 0.98) and central pathologist (AUC = 0.98) and had similar AUCs for the presence of EoE-related endoscopic features to pathologists' assessment. Average eosinophils per epithelial unit area had similar performance compared to AI high-power field-based analysis. Our newly developed AI model can accurately identify, quantify, and score several of the main histopathologic features in the EoE spectrum, with agreement regarding EoEHSS scoring which was similar to that seen among GI pathologists., (Copyright © 2023. Published by Elsevier Inc.)

Background & Aims: Guidelines recommend measuring antibody (Ab) titers to hepatitis B virus (HBV) after vaccination for patients with inflammatory bowel disease (IBD) or celiac disease (CD) ("patients with IBD/CD") and revaccinating when titers are low. Few data, however, support this recommendation. We aimed to compare effectiveness of HBV vaccination (immunity and infection rates) for patients with IBD/CD vs matched referents., Methods: Using the Rochester Epidemiology Project, we performed a retrospective cohort study of patients first diagnosed with IBD/CD (index date) while residing in Olmsted County, Minnesota, from January 1, 2000, through December 31, 2019. HBV screening results were obtained from health records., Results: In 1264 incident cases of IBD/CD, only 6 HBV infections were diagnosed before the index date. A total of 351 IBD/CD cases had documented receipt of 2 or more HBV vaccines before their index date and had hepatitis B surface antigen Ab (anti-HBs) titers measured after their index date. The proportion of patients with HBV-protective titers (≥10 mIU/mL) decreased with time before plateauing, with protective titer rates of 45% at 5 up to 10 years and 41% at 15 up to 20 years after the last HBV vaccination. The proportion of referents with protective titers also decreased with time and was consistently higher than the levels of patients with IBD/CD within 15 years after the last HBV vaccination. However, no new HBV infection developed in any of 1258 patients with IBD/CD during a median follow-up of 9.4 years (interquartile range, 5.0-14.1 years)., Conclusions: Routine testing of anti-HBs titers may not be indicated for fully vaccinated patients with IBD/CD. Additional studies are needed to confirm these findings in other settings and populations., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objectives: Patients with Trisomy 21 (T21) commonly have gastrointestinal symptoms and diseases that prompt evaluation with esophagogastroduodenoscopy (EGD). Our objective is to characterize duodenal histological abnormalities in these patients when undergoing EGD. A secondary aim is to explore associations of histologic findings with different therapies., Methods: Patients 30 years old or younger with T21 who underwent EGD from 2000 to 2020 at 6 hospitals were included in this retrospective cohort study. Duodenal biopsies were categorized based on reported histopathology findings as normal or abnormal. Abnormal pathology reports were reviewed and categorized into villous atrophy (VA) and duodenitis without VA. The VA group was further categorized based on the presence or absence of celiac disease (CD)., Results: We identified 836 patients with T21 who underwent EGD, 419 (50.1%) of whom had duodenal histologic abnormalities. At the time of the first (index) abnormal duodenal biopsy, 290 of 419 had VA and of those, 172 of 290 met CD diagnostic criteria, while 118 of 290 did not meet CD criteria (nonspecific VA). Among the patients with an abnormal biopsy, acid suppression at the time of the index biopsy was less common in patients with VA-CD compared to patients without VA or patients with nonspecific VA (12.2% vs 45.7% vs 44.9%)., Conclusions: Half of the T21 patients in this cohort had abnormal duodenal biopsies including a subgroup with nonspecific VA. In this cohort, acid suppression use was more prevalent in patients with abnormalities other than CD., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Patient satisfaction (PS) surveying has become a commonly used measure of physician performance, but little is known about the impact on pediatricians. To investigate our hypothesis that PS surveys negatively impact pediatricians, we conducted a survey at an academic children's medical center. Of 155 eligible physicians, 115 responded (response rate 74%). Two-thirds (68%) did not find the PS score report useful and 88% did not feel that PS scores accurately reflect the physician's clinical ability. A third reported ordering tests, medications, or consultations due to pressure for higher PS scores. In addition, one-third agreed that PS surveys contribute to burnout and make it difficult to practice meaningful medicine. Overall, PS score reporting has a negative impact on pediatricians, especially those who are female, BIPOC (Black, Indigenous, and People of color), subspecialists, younger, and attended non-US medical schools. Further investigation into improved methods for providing feedback to pediatric physicians is warranted.

Objectives: Mucosal injury in celiac disease (CD) patients can be patchy, and up to 12% of CD patients can have mucosal changes limited to the duodenal bulb. Hence, recent guidelines recommend obtaining bulb biopsies in addition to distal duodenum. This study aimed to describe a cohort of children with isolated bulb CD and assess the benefit of separating bulb biopsies., Methods: A retrospective chart review between January 2011 and January 2022 at 2 medical centers was conducted. We included children with CD who underwent endoscopy with separated biopsies from the bulb and distal duodenum. A blinded pathologist performed Marsh-Oberhuber grading on selected cases., Results: We identified 224 CD patients, of which 33 (15%) had histologically confirmed isolated bulb CD. Patients with isolated bulb CD were older at diagnosis (10 vs 8 years; P = 0.03). Median anti-tissue transglutaminase immunoglobulin A (TTG IgA) level was lower in isolate bulb CD (2.8 vs 16.7 times the upper limit of normal [ULN], P < 0.001). Almost 88% (29/33) of isolated bulb CD patients had an anti-TTG IgA value of less than 10 times the ULN. Time to anti-TTG IgA normalization (mean 14 months) was similar between the 2 groups. A pathologist review of diagnostic biopsies could not distinguish between the bulb and distal duodenum biopsies in approximately one-third of the reviewed samples., Conclusions: Separating bulb from distal duodenum biopsies can be considered during CD diagnosis, particularly in children with anti-TTG IgA levels less than 10 times the ULN. Larger prospective cohorts are needed to decide whether isolated bulb CD is a unique cohort or an early stage of the conventional CD., Competing Interests: J.A.M. reports grants from Nexpep/ImmusanT, National Institutes of Health, Immunogenix, Takeda Pharmaceutical, Allakos, Provention Bio, Oberkotter Foundation, and Kanyos/Anokion and consultancy fees from Johnson & Johnson, Bristol Myers Squibb, Intrexon Corporation, Dren Bio, Neoleukin, Reistone Pharma, Immunic Therapeutics, Senda Biosciences, Brightseed Bio, Chugai Pharma, Kanyos, Alimentiv, Equillium, Ukko, Vial Health Technologies and have received royalties from Torax Medical, and Evelo. The remaining authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: We sought to evaluate the safety and effectiveness of fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (CDI) in pediatric immunocompromised (IC) patients., Methods: This is a multicenter retrospective cohort study of pediatric participants who underwent FMT between March 2013 and April 2020 with 12-week follow-up. Pediatric patients were included if they met the definition of IC and were treated with FMT for an indication of recurrent CDI. We excluded patients over 18 years of age, those with incomplete records, insufficient follow-up, or not meeting study definition of IC. We also excluded those treated for Clostridioides difficile recurrence without meeting the study definition and those with inflammatory bowel disease without another immunocompromising condition., Results: Of 59 pediatric patients identified at 9 centers, there were 42 who met inclusion and no exclusion criteria. Included patients had a median age of 6.7 years. Etiology of IC included: solid organ transplantation (18, 43%), malignancy (12, 28%), primary immunodeficiency (10, 24%), or other chronic conditions (2, 5%). Success rate was 79% after first FMT and 86% after 1 or more FMT. There were no statistically significant differences in patient characteristics or procedural components when patients with a failed FMT were compared to those with a successful FMT. There were 15 total serious adverse events (SAEs) in 13 out of 42 (31%) patients that occurred during the follow-up period; 4 (9.5%) of which were likely treatment-related. There were no deaths or infections with multidrug resistant organisms during follow-up and all patients with a SAE fully recovered., Conclusions: The success rate of FMT for recurrent CDI in this pediatric IC cohort is high and mirrors data for IC adults and immunocompetent children. FMT-related SAEs do occur (9.5%) and highlight the need for careful consideration of risk and benefit., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background  It is not clear if the increase in the number of esophagogastroduodenoscopies (EGDs) performed has any significant effect on the rate of lymphocytic duodenosis (LD) reporting in children and adolescents and whether it correlates with abnormal gastric and/or esophageal pathology." Methods  We performed a single-center retrospective study using the Mayo Clinic electronic health record and pathology database. We reviewed all EGD procedures performed in children and adolescents (<18 years) between January 1, 2000, and December 31, 2018, and identified two groups, the LD group and matched age and sex control group (normal duodenal biopsies). We evaluated the correlation of LD rate with the yearly number of EGDs performed and the presence of abnormal gastric and/or esophageal pathology. Results  Of 11,870 EGDs performed, we identified 338 (3%) individuals with LD and 390 (3%) randomly selected controls, with a mean (SD) age of 9.6 (5.3) and 11.7 (5.0) years, respectively. Based on logistic regression analysis, abnormal gastric histology was associated with the presence of LD when compared with controls (odds ratio, 2.85; 95% CI, 2.05-3.97; P  < 0.001). The rate of LD-positive biopsies per year was highly correlated with the number of EGDs performed (ρ = 0.931; 95% CI, 0.826-0.974; P  < 0.001). Conclusion  The rate of LD reporting is correlated with the number of EGDs performed and is more likely seen in children and adolescents with abnormal gastric histology., Competing Interests: Conflict of Interest None declared., (Syrian American Medical Society. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background: In an attempt to provide quantitative, reproducible, and standardized analyses in cases of eosinophilic esophagitis (EoE), we have developed an artificial intelligence (AI) digital pathology model for the evaluation of histologic features in the EoE/esophageal eosinophilia spectrum. Here, we describe the development and technical validation of this novel AI tool., Methods: A total of 10 726 objects and 56.2 mm 2 of semantic segmentation areas were annotated on whole-slide images, utilizing a cloud-based, deep learning artificial intelligence platform (Aiforia Technologies, Helsinki, Finland). Our training set consisted of 40 carefully selected digitized esophageal biopsy slides which contained the full spectrum of changes typically seen in the setting of esophageal eosinophilia, ranging from normal mucosa to severe abnormalities with regard to each specific features included in our model. A subset of cases was reserved as independent "test sets" in order to assess the validity of the AI model outside the training set. Five specialized experienced gastrointestinal pathologists scored each feature blindly and independently of each other and of AI model results., Results: The performance of the AI model for all cell type features was similar/non-inferior to that of our group of GI pathologists (F1-scores: 94.5-94.8 for AI vs human and 92.6-96.0 for human vs human). Segmentation area features were rated for accuracy using the following scale: 1. "perfect or nearly perfect" (95%-100%, no significant errors), 2. "very good" (80%-95%, only minor errors), 3. "good" (70%-80%, significant errors but still captures the feature well), 4. "insufficient" (less than 70%, significant errors compromising feature recognition). Rating scores for tissue (1.01), spongiosis (1.15), basal layer (1.05), surface layer (1.04), lamina propria (1.15), and collagen (1.11) were in the "very good" to "perfect or nearly perfect" range, while degranulation (2.23) was rated between "good" and "very good"., Conclusion: Our newly developed AI-based tool showed an excellent performance (non-inferior to a group of experienced GI pathologists) for the recognition of various histologic features in the EoE/esophageal mucosal eosinophilia spectrum. This tool represents an important step in creating an accurate and reproducible method for semi-automated quantitative analysis to be used in the evaluation of esophageal biopsies in this clinical context., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier Inc. on behalf of Association for Pathology Informatics.)

Background and Aims: Collagenous gastritis (CG) is a rare disorder characterized by subepithelial collagen deposition in the stomach. Standard medications have been only moderately successful in treating CG. We report results of a large, retrospective, open-label noncontrolled study of topical budesonide for CG, with an aim of establishing an alternative therapy for the disease., Methods: We identified patients treated for CG at Mayo Clinic (2000-2017) with topically targeted budesonide (TTB) in 2 formulations: open-capsule budesonide or compounded immediate-release budesonide capsule. Demographic, clinical, biochemical, and histologic variables were assessed for all patients before and after treatment., Results: We identified 64 patients with CG (50 adults, 14 children). Most were female (68%), mean age was 41 ± 22.8 years, and body mass index was 23.1 ± 5.9 kg/m 2 . In most pediatric patients, CG presented with abdominal pain and anemia; in adults, CG presented more often with weight loss (P < .001). Collagenous sprue or colitis were more common in patients >50 years of age (83%) vs those 19-50 years of age (27%) or <19 years of age (50%) (P < .001). Of the patients treated with TTB, 89% had a clinical response to TTB (42% complete, 46% partial), and 88% had a histologic response (53% complete, 33% partial)., Conclusions: Adults and children with CG have a wide variety of symptoms, and notably, TTB therapy produced clinical and histologic improvement after other therapy had failed., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: We aimed to assess the efficacy of intrapyloric botulinum toxin A injection (IPBTI) in children with and without gastroparesis and to perform a meta-analysis and review of the literature., Methods: We retrospectively searched our electronic health records to identify children (aged < 18 years) who underwent an esophagogastroduodenoscopy with IPBTI between 2007 and 2018 for persistent upper gastrointestinal tract symptoms. We included children with and without gastroparesis and excluded children with a history of gastrointestinal surgery, gastrointestinal obstruction, or mucosal disease that could explain their symptoms. A meta-analysis including our study findings was performed., Results: We identified 20 children (mean [standard deviation] age, 9.7 [5.8] years; 14 [70%] girls) with upper gastrointestinal symptoms who underwent IPBTI at our institution during the study period. Of the 20 children, 17 (85%) underwent gastric emptying scintigraphy, only nine (53%) of whom had gastroparesis. Response to IPBTI was reported in ten children (50%). Response to IPBTI did not differ by the presence of gastroparesis in included children (p = 0.64). Repeated IPBTI was performed in four children who had a response to the first injection; all four reported no benefit from the second IPBTI. There were no reported complications of IPBTI in our cohort. The meta-analysis indicated that 68% (95% confidence interval 59-78) of patients had a response to IPBTI, regardless of the presence of gastroparesis; 66% (95% confidence interval 53-78) of patients who had gastroparesis had a response to IPBTI., Conclusions: Intrapyloric botulinum toxin A injection is safe in children and can offer transient relief for patients with refractory upper gastrointestinal symptoms with and without gastroparesis., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objectives: Nutrition support is essential in improving outcome and survival in children on extra corporal membranous support (ECMO). We aim to evaluate the association between the timing of enteral nutrition (EN) initiation and its impact on outcome., Methods: We retrospectively reviewed the electronic health records of children (≤18 years) from November 2014 to November 2019 who were on veno-arterial ECMO for ≥48 hours. Abstracted data included demographics, ECMO indication and duration, timing of EN initiation, change in weight-for-age z score (WAZ), and survival rate. The vasoactive-inotropic score (VIS) was calculated to assess illness acuity., Results: We identified 76 children with median age (interquartile range [IQR]) of 0.3 years (0-2.6), 46 of which were infants (59%) who required ECMO for a median (IQR) of 10 days (6-22). Thirty-six (47%) survived to hospital discharge. EN was initiated in 55 (72%) of patients while on ECMO. EN initiation by day 3 of ECMO was positively associated with survival ( P = 0.0438). VIS at the time of EN initiation was lower in surviving infants ( P = 0.022). Children who achieved enteral autonomy were more likely to survive ( P = 0.0024). Survivors had greater WAZs at ECMO completion ( P = 0.0004)., Conclusions: Initiation of EN by day 3 of ECMO and at a lower VIS is associated with greater likelihood of survival., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Purpose: The Mayo-Baylor RIGHT 10K Study enabled preemptive, sequence-based pharmacogenomics (PGx)-driven drug prescribing practices in routine clinical care within a large cohort. We also generated the tools and resources necessary for clinical PGx implementation and identified challenges that need to be overcome. Furthermore, we measured the frequency of both common genetic variation for which clinical guidelines already exist and rare variation that could be detected by DNA sequencing, rather than genotyping., Methods: Targeted oligonucleotide-capture sequencing of 77 pharmacogenes was performed using DNA from 10,077 consented Mayo Clinic Biobank volunteers. The resulting predicted drug response-related phenotypes for 13 genes, including CYP2D6 and HLA, affecting 21 drug-gene pairs, were deposited preemptively in the Mayo electronic health record., Results: For the 13 pharmacogenes of interest, the genomes of 79% of participants carried clinically actionable variants in 3 or more genes, and DNA sequencing identified an average of 3.3 additional conservatively predicted deleterious variants that would not have been evident using genotyping., Conclusion: Implementation of preemptive rather than reactive and sequence-based rather than genotype-based PGx prescribing revealed nearly universal patient applicability and required integrated institution-wide resources to fully realize individualized drug therapy and to show more efficient use of health care resources., Competing Interests: Conflict of Interest Liewei Wang, John Logan Black III, and Richard M. Weinshilboum are cofounders of and stockholders in OneOme, LLC, which was used only to return results to the study participants. Additionally, John Logan Black III and Mayo Clinic Ventures have applied for a patent on the CNVAR software cited in this study as well as the methodology upon which the software is based. All other authors declare no conflicts of interest., (Copyright © 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of our study was to assess the response to hepatitis B virus (HBV) vaccination and the risk of HBV infection in patients with celiac disease (CD)., Patients and Methods: We performed a cross-sectional study using the National Health and Nutrition Examination Survey (NHANES) database (2009-2014) to assess the rate of HBV vaccination, immune response, and HBV infection risk in patients with and without CD. We also determined the rate of HBV infection via retrospective analysis of two cohorts: patients seen at Mayo Clinic (1998-2021), and a stable longitudinally observed cohort, the Rochester Epidemiology Project (REP; 2010-2020)., Results: Based on the NHANES data, the rate of HBV infection in the United States was 0.33% (95% confidence interval 0.25-0.41). Of 93 patients with CD, 46 (49%) were vaccinated for HBV and of the remaining 19,422 without CD, 10,228 (53%) were vaccinated. Twenty-two (48%) vaccinated patients with CD had HBV immunity and 4405 (43.07%) vaccinated patients without CD had HBV immunity, which was not statistically different. In NHANES data, there were no cases of HBV infection in patients with CD. During the study period, 3568 patients with CD were seen at Mayo Clinic and 3918 patients with CD were identified using the REP database. Of those patients with CD, only four (0.11%) at Mayo Clinic and nine (0.23%) of the REP patients had HBV infection., Conclusion: The rate of HBV vaccination and immunity was similar in individuals with and without CD. Predictably, no increased risk of HBV infection was detected in CD patients. These results do not support screening and revaccination practice for HBV immunity in patients with CD within the United States., Competing Interests: Dr Jacobson serves as a member of two safety review committees for post-licensure safety studies of human papillomavirus vaccines conducted by Merck & Co. and a member of an external data monitoring committee for a series of trials of a novel pneumococcal conjugate vaccine also conducted by Merck & Co. The other authors report no conflicts of interest., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objective: Extracorporeal membrane oxygenation (ECMO)-associated direct hyperbilirubinemia (DHB) is likely multifactorial. The objective of this study is to assess the frequency and risk factors for developing direct hyperbilirubinemia while on ECMO, and its implication on the mortality of children., Methods: We performed a retrospective study between January 2010 and January 2020. Using Mayo Clinic electronic health record, we identified children (<18 years) who required veno-arterial (VA) ECMO support. Demographics, ECMO indication, laboratory findings, and outcomes were abstracted. Illness acuity scores, including vasoactive-ionotropic score (VIS), were used to assess disease severity at time of admission. Study cohort was divided into two groups: children who developed direct hyperbilirubinemia (DHB) on ECMO and children who did not (control). DHB was defined as direct bilirubin (DB) of >1.0 mg/dL. Disease acuity and mortality rates were compared between the two groups. Logistic regression was used to analyze the risk of mortality independent of potential confounding variables., Results: We identified 106 children who required ECMO support during the study period. Of those, 36 (34%) children developed DHB on ECMO. Illness acuity scores were significantly higher in the DHB group on ECMO day 2 (P = 0.046) and day 7 (P = 0.01). Mortality rate was higher in the DHB group 72%, versus 29% in the control group (P < 0.001)., Conclusion: DHB was associated with a higher mortality rate than the control group., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: Children with perianal fistulizing Crohn disease require intensive medical management but also have a higher risk for subsequent surgical interventions., Objective: We performed a retrospective study to identify patient factors and perianal anatomical features by pelvic MR that are associated with surgical interventions in these children., Materials and Methods: We included children with Crohn disease and perianal fistula who underwent pelvic MR with available, archived images and collected demographic, clinical and laboratory data. Radiologists reviewed pelvic MR exams and identified Park classification and additional anatomical features of perianal fistulas, including fistula branching, horseshoe ramifications, abscess, inflammatory mass, supralevator extension, anal sphincter damage, proctitis and posterior anal space involvement. We performed univariate and subsequent multivariate analysis to determine features associated with subsequent surgical intervention., Results: Ninety-nine children with Crohn disease underwent pelvic MR. In this cohort, 69 children had no surgical interventions prior to baseline MRI, with subsequent median clinical follow-up of 5.5 years. Univariate analysis demonstrated that branching (P=0.009), supralevator extension (P=0.015) and anal sphincter damage (P=0.031) were significantly associated with subsequent surgical intervention. Age at baseline MRI was also associated with intervention (hazard ratio [HR] every 5 years: 2.13; 95% confidence interval [CI]: 1.18-3.83; P=0.012). A multivariable model identified only fistula branching (HR: 2.31; 95% CI: 1.28-4.15; P=0.005) and age (HR: 5.18; CI: 1.57-17.14; P=0.007) as independent predictors of subsequent surgery. No demographic, clinical or laboratory parameter predicted subsequent surgical intervention., Conclusion: Age and anatomical MR features indicating fistula complexity (branching, supralevator extension) and sphincter damage confer a higher risk of subsequent surgical intervention in children with perianal Crohn disease., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: The authors report no conflicts of interest.

Background As the use of antibiotics during the peripartum period increases, the incidence of autoimmune disorders and autism spectrum disorders (ASDs) is also increasing. In this study, we aim to assess if antibiotic exposure during the peripartum period affects the incidence of autoimmune diseases and ASD in the offspring. Methods We identified children (< 18 years of age) born in Olmsted County from January 1, 2003 through December 31, 2012. Offspring with celiac disease (CD), inflammatory bowel disease (IBD), or ASD diagnoses were matched to two controls on birth date, index date, mother's age at delivery, and sex. Data from the mother's medical records were retrieved to determine peripartum antibiotics use. Results A total of 242 cases and 484 matched controls were included in this study. Median age at the last follow-up was 11.3 years (range: 0.5-14.9), 73% were males in both groups. Odds of CD diagnosis was not statistically different between vaginal delivery with antibiotics compared with vaginal delivery with no antibiotics (odds ratio [OR] = 0.76, 95% confidence interval [CI]: 0.32-1.85), similarly in IBD (OR = 2.41, 95% CI: 0.53-10.98) and ASD (OR = 1.00, 95% CI:0.55-1.79). Preeclampsia or eclampsia was associated with offspring CD (OR = 3.20, 95% CI: 1.05-9.78). Smoking history and diabetes mellitus were associated with offspring ASD (OR = 1.84, 95% CI: 1.22-2.77 and OR = 2.01, 95% CI: 1.03-3.91, respectively). Conclusion In this cohort, we found no statistically significant association between peripartum antibiotics exposure and the development of CD, IBD, or ASD., (Syrian American Medical Society. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Competing Interests: AUTHOR DISCLOSUREDrs Ariagno, Hull, and Absah and Ms Jeeji have disclosed no financial relationships relevant to this article. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.

Objectives: Excessive fecal bile acids in adults have been associated with diarrhea-predominant irritable bowel syndrome (IBS-D), but their role in pediatric IBS-D is unknown. Serum markers including 7α-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor-19 (FGF-19) were validated in adults to detect bile acid diarrhea (BAD) compared to 48-hour fecal bile acid collection (48FBA). Our aims were to assess fasting serum C4 and FGF-19 and 48FBA in a pediatric population, to compare measurements in IBS-D patients and healthy controls (HC), and to determine the prevalence of BAD among children with IBS-D., Methods: Using a cross-sectional design, 26 patients with IBS-D and 56 HC were recruited in two pediatric tertiary care centers. Fasting serum C4 and FGF-19 and 48FBA were obtained. Participants completed a 7-day bowel diary coinciding with stool collection. Associations were analyzed using Spearman correlations., Results: Mean age was 14.7 ± 2.5 years (42.3% female) in IBS-D and 12.6 ± 2.4 years (39.3% female) in HC. There was a significant correlation of C4 with 48FBA (r = 0.48, P < 0.05) and an inverse association with FGF-19 (r = -0.43, P < 0.05). No significant differences were noted in C4 (P = 0.32), FGF-19 (P = 0.1), or 48FBA (P = 0.5) between IBS-D and HC groups; however, 20% of IBS-D patients had elevated C4 and 28% had low FGF-19 values.Fecal primary BA was significantly correlated with stool frequency (r = 0.45, P < 0.002)., Conclusions: Correlations of C4 with 48FBA and FGF-19 are confirmed in a pediatric population. Twenty percent of pediatric patients with IBS-D had abnormal fasting serum C4. This serum test could be applied to identify BAD in pediatric IBS-D., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

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., (Copyright © 2021 by The American College of Gastroenterology.)

Background: Lymphocytic duodenosis (LD) defined as increased intraepithelial lymphocytes >25 intraepithelial lymphocytes (IELs) per 100 epithelial cells with normal villous architecture is associated with many gastrointestinal (GI) disorders. We aim to assess the rate and outcome of LD in children and perform a systematic review., Method: We reviewed all children (<18 years) who underwent esophagogastroduodenoscopy (EGD) with duodenal biopsy between January 2000 and June 2019 to identify LD cases and control group. Demographics, clinical, and pathologic information were reviewed and recorded. A systematic review including our findings was performed., Results: During the study period 12,744 children underwent an EGD with biopsies. Of those, we identified 426 children with LD (3%) and 474 controls. The median age in years was 10.7 and 12.6 and there were 254 (60%) and 278 (59%) girls in the LD and control group, respectively. The most common presenting symptoms in both groups were abdominal pain (52%), gastroesophageal acid reflux disease (18%), diarrhea (16%), and vomiting (12%). Diarrhea (21% vs 12%, P < 0.001) and constipation (2% vs 0.4%, P = 0.021) were statistically different between the LD and control group, respectively. Median follow-up (range) is 3.6 (0.0, 190.9) and 3.1 (0.0, 194.2) in the LD and control group, respectively. CD (5% vs 0%, P < 0.001), Crohn disease (9% vs 3%, P = 0.003) and Helicobacter pylori gastritis (3% vs 1%, P = 0.021) were more common in the LD group., Conclusions: The Rate of LD in children is similar to reported rate in adults. In the absence of Crohn disease, CD or H. Pylori, LD seems to be a benign and transient histologic finding in children., (Copyright © 2020 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background & Aims: Fecal microbiota transplantation (FMT) is used commonly for treatment of Clostridioides difficile infections (CDIs), although prospective safety data are limited and real-world FMT practice and outcomes are not well described. The FMT National Registry was designed to assess FMT methods and both safety and effectiveness outcomes from North American FMT providers., Methods: Patients undergoing FMT in clinical practices across North America were eligible. Participating investigators enter de-identified data into an online platform, including FMT protocol, baseline patient characteristics, CDI cure and recurrence, and short and long-term safety outcomes., Results: Of the first 259 participants enrolled at 20 sites, 222 had completed short-term follow-up at 1 month and 123 had follow-up to 6 months; 171 (66%) were female. All FMTs were done for CDI and 249 (96%) used an unknown donor (eg, stool bank). One-month cure occurred in 200 patients (90%); of these, 197 (98%) received only 1 FMT. Among 112 patients with initial cure who were followed to 6 months, 4 (4%) had CDI recurrence. Severe symptoms reported within 1-month of FMT included diarrhea (n = 5 [2%]) and abdominal pain (n = 4 [2%]); 3 patients (1%) had hospitalizations possibly related to FMT. At 6 months, new diagnoses of irritable bowel syndrome were made in 2 patients (1%) and inflammatory bowel disease in 2 patients (1%)., Conclusions: This prospective real-world study demonstrated high effectiveness of FMT for CDI with a good safety profile. Assessment of new conditions at long-term follow-up is planned as this registry grows and will be important for determining the full safety profile of FMT., (Copyright © 2021. Published by Elsevier Inc.)

Increased gut permeability has been suggested in patients with celiac disease (CD). We aimed to compare gut permeability in children using the lactulose/rhamnose permeability test. We prospectively recruited 55 children into 3 groups; 27 in group 1 (children with newly diagnosed celiac disease, 12 in group 2 (siblings of children with celiac disease) and 16 in group 3 (control group). The median age of participants was 11 years 2 months in group 1, 9 years 5 months in group 2 and 10 years 3 months in group 3. Standardized median delta rhamnose was lower in CD group as compared to control group (147.5 vs 3153.1, P  = 0.040). The low median rhamnose absorption in children with celiac disease as compared to other groups suggests that this test can differentiate between damaged and healthy mucosa, hence can it potentially can be used as a noninvasive test of mucosal healing in children with celiac disease., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Current screening guidelines in North America for celiac disease recommend additional IgG based testing for younger children. Our multicenter retrospective study showed that the anti-tissue transglutaminase IgA antibody test should be the recommended initial test in all children, including those ≤24 months of age., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Orthostatic intolerance (OI) and autonomic dysfunction (AD) are common in adolescents and young adults. Patients experience multisystem symptoms including gastrointestinal (GI), postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension (OH), or only symptoms of OI (SOI) without significant findings on 70-degree head-up tilt testing (HUT). We hypothesize that patients with POTS, OH, and SOI show differences in GI symptoms and motility test and that heart rate (HR) changes on HUT predict severity of GI dysmotility., Study Design: From medical records of patients (<18 years) with OI, we collected demographics, presenting symptoms, GI manifestations, and GI motility testing. Data were compared between the 3 groups (POTS, OH, and SOI). We assessed changes in HR on HUT with changes on GI motility evaluation., Results: Two hundred twenty-nine patients were included (73% females). Abdominal pain (65%), nausea (49%), vomiting (18%), and constipation (24%) were the most common GI symptoms. In patients who had motility evaluation, there were 27% (53/193) with delayed gastric emptying (GE) at 4 hours, 35% (32/92) with delayed colonic transit (CT), 55% (17/31) with reduced gastric accommodation (GA), and 75% (21/28) with dyssynergic defecation (DD). Among 100 POTS, 34 OH, and 95 SOI patients, no significant differences in GI symptoms or motility tests were identified and HR changes on HUT were not associated with changes on motility tests., Conclusion: GI symptoms are frequent in adolescents with OI and are associated with delayed GE, reduced GA, delayed CT, and presence of DD., (© 2020 John Wiley & Sons Ltd.)

Introduction: Immunocompromised children are susceptible to infectious diarrhea. Oral administration of human serum immunoglobulins to treat immunocompromised patients with viral gastroenteritis caused by viruses like rotavirus and norovirus has been reported., Objective: The aim of this study was to assess the efficacy of oral immunoglobulin (OIG) in treating hospitalized immunocompromised children with diarrheal illness., Methods: We conducted a retrospective cohort review of the Mayo Clinic electronic medical records from January 1, 2005, through April 30, 2019. We included children who were immunocompromised and received OIG as a treatment for a diarrheal illness that was classified as acute (< 4 weeks) or chronic (> 4 weeks) at the time of their treatment. Response to therapy was defined by 50% reduction in stool output., Results: Nineteen children were identified (11 males); average age at the time of treatment was 11 (0.25-18) years. In the acute diarrhea cohort, the mean duration of symptoms was 9.5 days (4-21). In the chronic diarrhea cohort, the mean duration of symptoms was 41 days (28-90). All 19 children were treated with OIG with doses in the range of 100-300 mg/kg/day for 1-5 days. Eighteen patients (95%) had improvement. Overall average time to response was 3.1 (1-9) days after receiving the OIG., Conclusion: Oral administration of human serum immunoglobulin in immunocompromised children presenting with acute and chronic diarrheal illness appeared helpful in reducing stool output by 50% in the majority of patients.

Background: Patients with autoimmune disorders (ADs) are at increased risk for celiac disease (CD), but data are conflicting on the risk of ADs in treated patients with CD. We aimed to assess the incidence of ADs in treated patients with CD., Methods: Using the Rochester Epidemiology Project, we retrospectively searched for the medical records at Mayo Clinic and Olmsted Medical Center from January 1997 to December 2015 for patients with CD who met accepted diagnostic criteria. For each patient with CD, we identified 2 age and sex-matched controls during the same study period. The incidence rate of AD diagnosis 5 years after index date was calculated using Kaplan-Meier analysis for the CD cases and controls and compared using the log-rank test., Results: We identified 249 treated patients with CD during the study period and 498 matched controls, with mean (standard deviation) ages of 32 (22) years and 33 (22) years, respectively. One third of patients (n = 85) and controls (n = 170) were boys. Five years after the index date, 5.0% of patients with CD and 1.3% of controls had a de novo AD diagnosis (P = 0.006). In the presence of a prior AD, the cumulative risk of a de novo or additional AD was significantly higher in the CD group compared with controls (P < 0.001). Children had a significantly higher risk of AD development compared with adults (P = 0.010)., Conclusions: Treated patients with CD are at higher risk for the development of ADs. The risk of a new AD is higher in children, especially when >1 AD diagnosis exists.

Objective: To investigate the prevalence of first-degree relatives (FDRs) with celiac disease detected at screening and diagnostic significance of anti-tissue transglutaminase (anti-TTG)., Patients and Methods: We performed a retrospective cohort study of 104 patients with a diagnosis of celiac disease and their FDRs, collecting data from electronic records of Mayo Clinic and celiac disease registry from December 20, 1983, to May 22, 2017. We collected demographics, presenting symptoms, indication for testing, family history, number of other family members screened, biopsy reports, and results of serologic tests., Results: Of 477 FDRs identified, 360 were screened (mean screening rate per family, 79%±25%) and 160 FDRs (44.4%) were diagnosed with celiac disease, at a mean age 31.9±21.6 years (62% female). All diagnosed FDRs had positive anti-TTG titers. Clinical features were documented in 148 diagnosed FDRs, of those 9 (6%) had classic, 97 (66%) had non-classic symptoms, and 42(28%) had no reported symptoms. Histology reports were available from 155 FDRs: 12 (8%) had Marsh 1, 77 (50%) had Marsh 3a, and 66 (43%) had Marsh 3b. A level of anti-TTG greater than or equal to 2.75 of the upper limit of normal identified FDRs with villous atrophy with 87% sensitivity, 82% specificity, and a positive predictive value of 95%., Conclusion: In a retrospective cohort study of patients diagnosed with celiac disease, we found a high prevalence of celiac disease among screened FDRs. High anti-TTG titers associated with villous atrophy on small bowel biopsies, irrespective of symptoms., (Copyright © 2019 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate micronutrient deficiencies in a contemporary cohort of adult patients with newly diagnosed celiac disease (CD)., Patients and Methods: This is a retrospective study of prospective adults newly diagnosed with CD from January 1, 2000, through October 31, 2014, at Mayo Clinic. Micronutrient data were collected for tissue transglutaminase IgA, zinc, 25-hydroxy vitamin D, ferritin, albumin, copper, vitamin B 12 , and serum folate. Data were analyzed for absolute number of deficiencies and associations with age, sex, body mass index, presenting symptoms, and tissue transglutaminase IgA; each deficiency was assessed using logistic regression. Deficiencies were compared with age- and sex-matched controls from the National Health and Nutrition Examination Survey., Results: In total, 309 patients with CD (196 women and 113 men; mean age, 46.1±15.1 years; mean body mass index, 25.9 kg/m 2 ) were included. Weight loss was seen in only 25.2% (78/309) of patients. Zinc was deficient in 59.4% (126/212) of patients with CD compared with 33.2% (205/618) of controls (P<.001). Albumin was low in 19.7% (24/122) compared with 1.1% of controls (P<.001). Copper was low in 6.4% (13/204) compared with 2.1% (13/618) of controls (P=.003). Vitamin B 12 was low in 5.3% (13/244) compared with 1.8% (11/618) of controls (P=.004). Folate was low in 3.6% (6/159) compared with 0.3% (2/618) of controls (P=.002). 25-Hydroxy vitamin D was low in 19.0% (44/213) compared with 18% (111/618) of controls (P=.72). Ferritin was low in 30.8% (66/214) of patients; no NHANES controls were available for comparison for ferritin., Conclusion: Micronutrient deficiencies remain common in adults with CD despite increased nonclassic presentation. This study provides support for micronutrient assessment at the time of CD diagnosis., (Copyright © 2019 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Familial adenomatous polyposis (FAP) is a hereditary syndrome that can affect the entire GI tract. Current screening recommendations include EGD starting at age 25 to 30 years or earlier in symptomatic patients. However, few reports describe upper GI tract involvement in children with FAP that support the notion of early screening. The aim of our study is to understand the prevalence and severity of upper GI involvement in children with FAP., Methods: We performed a retrospective review of the Mayo Clinic records, between 1992 and 2016, to identify children with the diagnosis of FAP who underwent EGD examinations. A systematic review of the literature was performed to include published studies reporting children with FAP and upper GI findings., Results: The retrospective study included 69 children with a mean age of 13.5 years (range, 3-18). Thirty-six children (52%) had duodenal adenoma with low-grade dysplasia. Five children required an ampullectomy secondary to enlarged and polypoid ampullas. Combined with published studies, a total of 206 children with upper GI findings were identified, of which 87 (42%) had duodenal adenoma (1 had high-grade dysplasia). Meta-analysis of 5 series demonstrated duodenal adenoma detection rate of 39% (95% confidence interval, 21%-57%; I 2  = 85%)., Conclusions: The available data to date show that children with FAP can have clinically relevant lesions in the upper GI tract earlier than previously foreseen, suggesting that earlier screening may be indicated. Larger multicenter prospective studies are needed to determine the best approach and optimal age for EGD screening in children with FAP., (Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Although human leukocyte antigen (HLA)-DR and HLA-DQ genes and gluten play crucial roles in developing celiac disease (CD), most patients with these risk factors still do not develop CD, which indicates additional unrecognized risk factors., Objective: To determine the association between asthma and the risk of CD in children., Methods: We conducted a population-based retrospective case-control study in children who resided in Olmsted County, Minnesota. We identified children with CD (cases) between January 1, 1997, and December 31, 2014, and compared these with children without CD (controls) (1:2 matching). Asthma status was ascertained by using the predetermined asthma criteria (PAC) and the asthma predictive index (API). Data analysis included conditional logistic regression models and an unsupervised network analysis by using an independent phenome-wide association scan (PheWAS) data set., Results: Although asthma status as determined by using PAC was not associated with the risk of CD (odds ratio [OR] 1.4 [95% confidence interval {CI}, 0.8-2.5]; p = 0.2), asthma status by using the API was significantly associated (OR 2.8 [95% CI, 1.3-6.0]; p = 0.008). A subgroup analysis indicated that children with both asthma as determined by using PAC and a family history of asthma had an increased risk of CD compared with those without asthma (OR 2.28 [95% CI, 1.11-4.67]; p = 0.024). PheWAS data showed a cluster of asthma single nucleotide polymorphisms and patients with CD., Conclusion: A subgroup of children with asthma who also had a family history of asthma seemed to be at an increased risk of CD, and, thus, the third factor that underlies the risk of CD might be related to genetic factors for asthma. Heterogeneity of asthma plays a role in determining the risk of asthma-related comorbidity.

Objective: To assess the prevalence of gluten-free diet (GFD) among school-age children in Olmsted County, Minnesota, and compare it with the prevalence of celiac disease (CD) in the same age group., Methods: We performed a population-based study in Olmsted County using a survey to collect information from the six school districts in the county for the academic year 2014-2015. The survey contained questions to (1) assess the prevalence of GFD among school-age children in the public schools of Olmsted County; (2) assess the prevalence of CD among school-age children in Olmsted County; and (3) determine the indications for GFD in these children. We used the infrastructure of the Rochester Epidemiology Project (REP) to calculate the prevalence of CD in children aged 4-18 years in December 2014., Results: Using the REP data, we identified sixty patients with CD in the county aged 4-18 years; the prevalence of CD among school students in 2014 was 193.6/100,000. The prevalence of GFD in Olmsted County children, however, was higher, at 265/100,000 according to the survey from the school districts. The prevalence of GFD was highest in Rochester, the largest city. GFD was more common among children in secondary schools., Conclusion: According to our study, there are more children on GFD than the actual cases of CD in Olmsted County during the study period. This finding could be related to an increased number of children without CD who are following GFD for other indications., Competing Interests: There are no conflicts of interest.

Objectives: Celiac disease (CD) is a common immune-mediated disorder that affects up to 1% of the general population. Recent reports suggest that the incidence of CD has reached a plateau in many countries. We aim to study the incidence and altered presentation of childhood CD in a well-defined population., Methods: Using the Rochester Epidemiology Project, we retrospectively reviewed Mayo Clinic and Olmsted Medical Center medical records from January 1994 to December 2014. We identified all CD cases of patients ages 18 years or younger at the time of diagnosis. Incidence rates were calculated by adjusting for age, sex, and calendar year and standardizing to the 2010 US white population., Results: We identified 100 patients with CD. Incidence of CD has increased from 8.1 per 100,000 person-years (2000-2002) to 21.5 per 100,000 person-years (2011-2014). There was an increase in CD prevalence in children from 2010 (0.10%) to 2014 (0.17%). Thirty-four patients (34%) presented with classical CD symptoms, 43 (43%) had nonclassical CD, and 23 (23%) were diagnosed by screening asymptomatic high-risk patients. Thirty-six patients (36%) had complete villous atrophy, 51 (51%) had partial atrophy, and 11 (11%) had increased intraepithelial lymphocytes. Two patients were diagnosed without biopsy. Most patients (67%) had a normal body mass index, 17% were overweight/obese, and only 9% were underweight., Conclusions: Both incidence and prevalence of CD have continued to increase in children during the past 15 years in Olmsted County, Minnesota. Clinical and pathologic presentations of CD are changing over time (more nonclassical and asymptomatic cases are emerging).

Background: The association between celiac disease (CD) and eosinophilic esophagitis (EoE) has been the focus of multiple studies with variable results. Both diseases are immune mediated, and dietary triggers play a role in their pathogenesis., Objectives: The aim of the study was to analyze the risk of EoE in children with CD, assess the magnitude of association between CD and EoE in children, and report the characteristics and outcomes of children with both conditions., Methods: We conducted a retrospective study of the Mayo Clinic Electronic medical records between January 1, 1998 and December 31, 2015. Systematic review and meta-analysis of multiple databases was conducted to include studies reporting on the same association. Random-effects model was used to report pooled odds ratio (OR) and 95% confidence interval (CI)., Results: In this cohort study, of 10,201 children who underwent at least 1 endoscopy, 595 had EoE, and 546 had CD. The risk of having EoE was not increased in children with CD compared to those without CD (OR, 0.29; 95% CI, 0.154-0.545). Nine of 10 children improved with gluten-free diet, topical glucocorticosteroid, and/or elimination diet. One child lost to follow-up.Meta-analysis of 5 studies showed similar results (OR, 0.525; 95% CI, 0.364-0.797). A total of 45 cases in the literature had both CD and EoE (mean age, 10 years; 64% boys; majority presenting with abdominal pain, vomiting, and diarrhea)., Conclusions: Based on our cohort and the observational data, the diagnosis of CD in children is not associated with increased risk of EoE.

Objectives: Guidelines for diagnosing celiac disease (CD) recommend initial testing with a highly sensitive serologic test for anti-tissue transglutaminase immunoglobulin A antibodies (tTG IgA). When the probability of CD is high, IgA deficiency should be considered. The 2 approaches to address this include measuring "both tTG IgA and tTG IgG" or measuring "total IgA." We aim to assess the utility of an isolated positive tTG IgG result in diagnosing CD., Methods: We conducted a retrospective review of patients undergoing serologic testing for CD from January 1997 to June 2014. Patients with positive tTG IgG and negative tTG IgA were included. Moreover, all patients who had any other positive CD-specific serologic findings were excluded. Demographics, clinical presentation, tests, and biopsy results were recorded., Results: The indication for checking celiac serology was gastrointestinal symptoms in 172 of 233 patients, iron deficiency anemia in 12, and high-risk screening in 48. Small bowel biopsy was performed in 178 patients (77%); 160 had normal results and 18 had histologic changes suggestive of enteropathy. Nine patients had increased intraepithelial lymphocytes, and 9 had partial villous atrophy. Only 6 cases of CD were, however, confirmed. The utility of isolated tTG IgG in diagnosis of CD was low at 3% (6/178)., Conclusion: In this cohort of patients, the utility of isolated tTG IgG in diagnosing CD was low at 3%.

Background & Aims: In patients with positive results from serologic tests for celiac disease, analysis of tissues samples from the duodenal bulb, in addition to those from other parts of the small bowel, might increase the diagnostic yield. However, biopsies are not routinely collected from the duodenal bulb because of concerns that villous atrophy detected there could be caused by other disorders (Brunner glands or peptic duodenitis, gastric metaplasia, shorter villi, or lymphoid follicles). We investigated whether analysis of biopsies from duodenal bulbs of all patients undergoing endoscopy (a population with a low probability for celiac disease) increases diagnoses of celiac disease., Methods: We performed a retrospective analysis of data from 679 patients (63% female; mean age, 50 years) from whom duodenal bulb and small bowel biopsies were collected during endoscopy at 3 Mayo Clinic sites, from January 1, 2011 through December 31, 2011. Records were reviewed for age, sex, pathology findings, serology test results (HLA DQ2 or DQ), indications for biopsy analyses, and adherence to a gluten-free diet. Patients with celiac disease were identified on the basis of increased intraepithelial lymphocytosis, with or without villous atrophy and crypt hyperplasia, and results from serology tests. Findings from duodenal bulbs were compared with diagnoses using the Fisher exact test., Results: Of all patients undergoing endoscopy, 16 patients (2%) were found to have celiac disease. Analysis of the duodenal bulb biopsies identified 1 patient (0.1%) with celiac disease limited to this region. Of 399 patients whose celiac serology was not known before endoscopic examination, only 2 patients had histologic changes consistent with celiac disease but not limited to duodenal bulb. Abnormal duodenal histology was detected in 265 patients (39%), most commonly in the bulb (n = 241; P < .0001). Of abnormal bulb histologies, chronic peptic duodenitis was most common (observed in 114 patients, 47%). In patients with a normal distal duodenum (n = 576), the duodenal bulb had abnormal histology in 162 (28%)., Conclusions: In a low pretest probability cohort, separate sampling of the duodenal bulb had minimal effect on celiac disease detection. Abnormal histologic findings are more commonly detected in the duodenal bulb; although they do not seem to impair identification of celiac disease, their clinical implications are unclear., (Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.)