Efficacy of Fecal Microbiota Transplantation for Clostridium difficile Infection in Children.

BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is commonly used to treat Clostridium difficile infection (CDI). CDI is an increasing cause of diarrheal illness in pediatric patients, but the effects of FMT have not been well studied in children. We performed a multi-center retrospective cohort study of pediatric and young adult patients to evaluate the efficacy, safety, and factors associated with a successful FMT for the treatment of CDI. METHODS: We performed a retrospective study of 372 patients, 11 months to 23 years old, who underwent FMT at 18 pediatric centers, from February 1, 2004, to February 28, 2017; 2-month outcome data were available from 335 patients. Successful FMT was defined as no recurrence of CDI in the 2 months following FMT. We performed stepwise logistic regression to identify factors associated with successful FMT. RESULTS: Of 335 patients who underwent FMT and were followed for 2 months or more, 271 (81%) had a successful outcome following a single FMT and 86.6% had a successful outcome following a first or repeated FMT. Patients who received FMT with fresh donor stool (odds ratio [OR], 2.66; 95% CI, 1.39-5.08), underwent FMT via colonoscopy (OR, 2.41; 95% CI, 1.26-4.61), did not have a feeding tube (OR, 2.08; 95% CI, 1.05-4.11), or had 1 less episode of CDI before FMT (OR, 1.20; 95% CI, 1.04-1.39) had increased odds for successful FMT. Seventeen patients (4.7%) had a severe adverse event during the 3-month follow-up period, including 10 hospitalizations. CONCLUSIONS: Based on the findings from a large multi-center retrospective cohort, FMT is effective and safe for the treatment of CDI in children and young adults. Further studies are required to optimize the timing and method of FMT for pediatric patients-factors associated with success differ from those of adult patients.

Vitamin deficiencies in pediatric eosinophilic esophagitis: A systematic review.

BACKGROUND: Nutritional deficiencies are seen in patients with food allergy. Low vitamin D levels have been found in patients with atopic conditions. Eosinophilic esophagitis (EoE) is a chronic immune antigen-mediated disease found to be highly associated in patients with atopic disease and treated with dietary elimination with recommendations to utilize a dietician to prevent nutritional deficiencies. Nonetheless, the relationship between EoE and vitamin deficiency remains unclear. We aimed to systematically review the evidence to support a possible association between vitamin deficiency and eosinophilic esophagitis. METHODS: Electronic searches were performed with keywords relating to EoE and vitamins among pediatric patients in MEDLINE, EMBASE, and The Cochrane Library. Summary estimates were calculated. Citations were reviewed against pre-defined criteria. (Inclusion: human subjects, aged 0-18, with eosinophilic esophagitis. Exclusion: adults over 18 years, non-English papers). RESULTS: The search yielded 1707 studies. Five of these studies with a total of 137 pediatric patients were included in the systematic review. Outcome measures were assessed at different points in EoE treatment across studies. The single common outcome measure across all included studies was vitamin D. Reported prevalence of low vitamin D varied in these studies (0%-52%). Vitamin D levels of children with EoE both pre- and post-intervention were low. CONCLUSIONS: There is limited published literature on vitamin deficiencies associated with EoE both pre- and post-intervention. The limited data on vitamin D suggest that insufficiency or deficiency may be present in these patients, but it remains unclear whether deficiency is caused by diet. More prospective, well-defined studies, in addition to routine reporting on dietary intake and nutritional status, are needed to make any conclusions or recommendations for screening.

Impact of COVID-19 on Pediatric Gastroenterology Fellow Training in North America.

BACKGROUND: The COVID-19 pandemic has drastically changed healthcare systems and training around the world. The Training Committee of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition sought to understand how COVID-19 has affected pediatric gastroenterology fellowship training. METHODS: A 21 question survey was distributed to all 77 pediatric gastroenterology fellowship program directors (PDs) in the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition program director database via email on April 7. Responses collected through April 19, 2020 were analyzed using descriptive statistics. RESULTS: Fifty-one of 77 (66%) PDs from the United States, Canada, and Mexico responded to the survey. Forty-six of 51 (90%) PDs reported that they were under a "stay-at-home" order for a median of 4 weeks at the time of the survey. Two of the 51 (4%) programs had fellows participating in outpatient telehealth before COVID-19 and 39 of 51 (76%) at the time of the survey. Fellows stopped participating in outpatient clinics in 22 of 51 (43%) programs and endoscopy in 26 of 51 (52%) programs. Changes to inpatient care included reduced fellow staffing, limiting who entered patient rooms, and rounding remotely. Fellows in 3 New York programs were deployed to adult medicine units. Didactics were moved to virtual conferences in 47 of 51 (94%) programs, and fellows used various online resources. Clinical research and, disproportionately, bench research were restricted. CONCLUSIONS: This report provides early information of the impact of COVID-19 on pediatric fellowship training. Rapid adoption of telehealth and reduced clinical and research experiences were important changes. Survey information may spur communication and innovation to help educators adapt.

Pediatric Gastroenterology, Hepatology, and Nutrition Entrustable Professional Activities: Development of an Assessment Tool and Curricular Resources.

BACKGROUND: Entrustable professional activities (EPAs) are critical activities performed by medical professionals, which can be observed and assessed. Adding on to common EPAs for all pediatric subspecialty trainees, specialty-specific EPAs for pediatric gastroenterology, hepatology, and nutritional fellowship were developed by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) EPA Task Force. METHODS: Having developed specialty-specific EPAs, building EPA assessments is the next logical step, as EPAs are included under a larger umbrella of competency-based assessment. Thus, the NASPGHAN EPA Task Force and Training Committee collaborated on an assessment tool and associated curricular resources to aid in tracking trainees' progression to entrustment within individual EPAs and readiness for independent practice. RESULTS: This manuscript reports the development of an EPA assessment tool, including guiding principles and the theory behind the assessment tool, with a focus on simple, meaningful assessments that can provide crucial performance feedback to trainees. In addition, curricular resources were developed, based on the assessment tool, to support training. Ultimately, it is the hope of the NASPGHAN EPA Task Force and Training Committee that this tool can aid training programs in providing formative feedback for trainees, and can be used by training programs and clinical competency committees for summative evaluation.

Correlation Between Aeroallergen Levels and New Diagnosis of Eosinophilic Esophagitis in New York City.

OBJECTIVE: The relation between food allergies and eosinophilic esophagitis (EoE) is well established. Aeroallergens may also contribute to the development of EoE; however, there are limited data to support or refute this hypothesis. The objectives of this pilot study were to determine whether there is a seasonal variation in the onset of symptoms and/or diagnosis of EoE and whether these variations correlate with a specific pollen concentration within New York City. METHODS: We performed a retrospective chart review to identify all pediatric patients at New York Presbyterian Weill Cornell Medical Center diagnosed with EoE between 2002 and 2012. Sixty-six patients were identified and 28 were excluded. Cases were classified by both date of initial symptoms and date of histologic diagnosis. Pollen counts from a certified New York City counting station and the percentage of EoE cases were collated monthly and seasonally and compared. RESULTS: There was a seasonal variation in onset of symptoms and diagnosis of EoE, with the highest number of patients reporting onset of symptoms of EoE in July to September, and those being diagnosed with EoE in October to December. There was a seasonal correlation between peak levels of grass pollen and peak onset of EoE symptoms, which were both highest in July to September. The diagnosis of EoE peaked one season later. CONCLUSIONS: The study findings suggest that there is a correlation between specific aeroallergens and both the onset of symptoms and time of diagnosis of patients with EoE.

Using the Objective Structured Clinical Examination to Assess ACGME Competencies in Pediatric Gastroenterology Fellows.

BACKGROUND: The Accreditation Council for Graduate Medical Education has described 6 core competencies with which trainees should demonstrate proficiency. Using the Objective Structured Clinical Examination (OSCE), we aimed to assess 4 of these competencies among Pediatric Gastrointestinal (GI) fellows (PGs). METHODS: Eight first-year PGs from 6 medical centers in the New York area participated in a 4-station OSCE with trained standardized patient (SP) actors. The cases included an emergency department (ED) consult, or "ED Consult" for lower gastrointestinal bleeding; "Breaking Bad News" focusing on CF nutritional complications; "Second Opinion" for abdominal pain; "Transition of Care" for inflammatory bowel disease. At each station, attending faculty observed the encounters behind a 1-way mirror. SPs and faculties provided immediate feedback to the examined fellows. Previously validated OSCE checklists were used to assess performance. On completion, fellows attended debriefing sessions and completed surveys about the educational value. RESULTS: Median overall milestone competency scores were 6.9 (PC1), 4.8 (PC2), 5.9 (MK1), 5.7 (MK2), 6.4 (ICS1), 6.9 (Prof1), and 6.7 (Prof3). Overall, fellows score highest (7/9) on the inflammatory bowel disease "Transition of Care" case, found the "Breaking Bad News" Cystic Fibrosis OSCE to be the most challenging, and were most comfortable with the "ED Consult" OSCE, as a commonly encountered scenario. Overall, the fellows rated the educational value of the program highly. CONCLUSIONS: To our knowledge, although the OSCE has been validated in other medical fields, this is the first OSCE program developed for PGs fellows. These OSCEs have included Accreditation Council for Graduate Medical Education competencies, serving to assess fellows' skills in these areas while exposing them to challenging medical and psychosocial cases that they may not frequently encounter.

Non-invasive assessment of endothelial function in children with obesity and lipid disorders.

BACKGROUND: Digital tonometry is designed to non-invasively screen for endothelial dysfunction by the detection of impaired flow-induced reactive hyperaemia in the fingertip. We determined whether digital reactive hyperaemia correlated with risk factors for atherosclerosis in two groups of children at increased risk for endothelial dysfunction. METHODS: A total of 15 obese children and 23 non-obese, dyslipidaemic children, 8-21 years of age, were enrolled, and their medical histories, anthropometric measurements, carotid wall thickness by means of ultrasonography, and fasting blood samples for cardiovascular risk factors were obtained. The standard endoPAT index of digital reactive hyperaemia was modified to reflect the true peak response or the integrated response of the entire post-occlusion period. In each group, age, sex, pubertal status, carotid wall thickness, and multiple cardiovascular risk factors were tested as predictors of endothelial dysfunction. RESULTS: In the non-obese, dyslipidaemic group, but not in the obese group, both indices strongly correlated with height (r=0.55, p=0.007, by peak response) followed by weight, waist circumference, and age. In both groups, neither index of reactive hyperaemia significantly correlated with any other cardiovascular risk factor. CONCLUSIONS: Contrary to the known age-related increase in atherosclerosis, digital reactive hyperaemia increased with age and its correlates in non-obese, dyslipidaemic children and was not related to other cardiovascular risk factors in either group. The reason for the lack of this relationship with age in obese children is unknown. The age-dependent physiology of digital microvascular reactivity and the endothelium-independent factors controlling the peak hyperaemic response need further study in children with a wide age range.

Longitudinal diffusion-weighted imaging changes in children with small bowel Crohn's disease: preliminary experience.

PURPOSE: Crohn's disease has been associated with restricted diffusion in diseased small bowel segments on diffusion-weighted imaging (DWI). However, data addressing longitudinal changes in DWI findings and their potential clinical ramifications in the pediatric population are lacking. The purpose of this study was to follow DWI changes in diseased small bowel segments between serial magnetic resonance enterography (MRE) examinations, and to correlate these changes with other imaging parameters and clinical status. METHODS: This retrospective study evaluated patients less than 21 years of age undergoing serial MRE examinations including DWI for Crohn's disease involving the small bowel. All patients carried a diagnosis of Crohn's disease established by pathology or corroborative clinical and imaging findings. Longitudinal changes in mean apparent diffusion coefficient (ADC) values within the wall of affected small bowel lesions were recorded and normalized to both unaffected bowel and skeletal muscle. ADC changes were correlated with qualitative imaging phenotype, as reflected by a defined set of non-DWI imaging parameters, as well as with clinical disease activity. RESULTS: Seventeen lesions were evaluated longitudinally, distributed among 13 patients (9 boys and 4 girls, mean age at baseline 16.6 years), each of whom had two sequential MRE examinations. Lesions demonstrating a fibrostenotic imaging phenotype at follow-up MRE had a significantly lower change in mean ADC value between examinations than lesions that did not have a fibrostenotic imaging phenotype (p = 0.0005), an effect that persisted when ADC values were normalized to unaffected bowel and skeletal muscle. Across all studies, lesions with a fibrostenotic imaging phenotype had lower ADC values than those with an inflammatory imaging phenotype, which were in turn lower than those with a normal imaging phenotype (p = 0.0001). CONCLUSION: Patterns of longitudinal DWI changes in Crohn's disease may differ among small bowel lesions depending upon their specific natural histories. These findings may assist in the evaluation of the ADC value as a potential imaging surrogate when evaluating lesion status, particularly as it pertains to relative contributions of inflammation and fibrosis.

Delivering bad or difficult news. An innovative simulation-based education approach to prepare interdisciplinary fellowships.

BACKGROUND: There is limited data on the effectiveness of training interventions to improve the delivery of bad news. METHODS: This preliminary research included pre-post assessments and an open-ended survey to evaluate the effectiveness and perceived value of training on delivering bad news for 26 first- and second-year fellows from five adult and pediatric fellowship programs. RESULTS: There was a significant increase in faculty assessment scores (34.5 vs. 41.0, respectively, Z = -3.661, p < 0.001) and Standardized Patient (SP) assessment scores (37.5 vs .44.5, respectively, Z = -2.244, p = 0.025). Fellows valued having a standard framework to aid in the delivery of bad news; receiving targeted feedback and having the opportunity to apply their skills in a subsequent case. CONCLUSIONS: A one-hour, four-phase lesson plan that includes an individualized training approach and simulation do-overs can be effective and valuable for preparing fellows to deliver bad news.

Efficacy and Outcomes of Faecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection in Children with Inflammatory Bowel Disease.

BACKGROUND: Children with inflammatory bowel disease [IBD] are disproportionally affected by recurrent Clostridioides difficile infection [rCDI]. Although faecal microbiota transplantation [FMT] has been used with good efficacy in adults with IBD, little is known about outcomes associated with FMT in paediatric IBD. METHODS: We performed a retrospective review of FMT at 20 paediatric centres in the USA from March 2012 to March 2020. Children with and without IBD were compared with determined differences in the efficacy of FMT for rCDI. In addition, children with IBD with and without a successful outcome were compared with determined predictors of success. Safety data and IBD-specific outcomes were obtained. RESULTS: A total of 396 paediatric patients, including 148 with IBD, were included. Children with IBD were no less likely to have a successful first FMT then the non-IBD affected cohort [76% vs 81%, p = 0.17]. Among children with IBD, patients were more likely to have a successful FMT if they received FMT with fresh stool [p = 0.03], were without diarrhoea prior to FMT [p = 0.03], or had a shorter time from rCDI diagnosis until FMT [p = 0.04]. Children with a failed FMT were more likely to have clinically active IBD post-FMT [p = 0.002] and 19 [13%] patients had an IBD-related hospitalisation in the 3-month follow-up. CONCLUSIONS: Based on the findings from this large US multicentre cohort, the efficacy of FMT for the treatment of rCDI did not differ in children with IBD. Failed FMT among children with IBD was possibly related to the presence of clinically active IBD.

Positive association between Helicobacter pylori and gastroesophageal reflux disease in children.

OBJECTIVES: The role of Helicobacter pylori (H pylori) in gastroesophageal reflux disease (GERD) remains controversial, particularly in children, because there are limited published data. Adult studies suggested that H pylori infection may protect against GERD by causing atrophic gastritis, which leads to reduced gastric acid secretion. The objective of our study was to determine the role of H pylori infection in the development of GERD in a pediatric population. PATIENTS AND METHODS: A retrospective analysis of 420 patients (M:F = 214:206) who underwent esophagogastroduodenoscopy (EGD) with biopsies between January 2000 and April 2006 was conducted. Patient demographics, clinical indications for EGD and the prevalence of reflux esophagitis (RE), the biomarker for GERD, in 2 groups, H pylori positive and H pylori negative, were reviewed. The prevalence of RE in the H pylori-positive and H pylori-negative groups was further analyzed on the basis of sex and age (<1 year, 1-10 years, >10 years). The mean age of the study population was 8.2 years (range 0-20 years). The clinical indications for EGD were as follows: recurrent abdominal pain (n = 186, 44%), malabsorption (n = 80, 19%), persistent vomiting (n = 80, 19%), suspected eosinophilic gastrointestinal disorders (n = 63, 15%), and others such as upper gastrointestinal bleeding or inflammatory bowel disease surveillance (n = 11, 3%). Statistical analysis was performed by using chi test, Fisher exact test, and multivariate logistical regression analysis. RESULTS: Among the 420 patients, 16 patients (3.8%) were positive for H pylori and 167 patients (39.8%) were found to have RE. Thirteen patients with H pylori were found to have histologic evidence of RE. The prevalence of RE in the H pylori-positive population was 81.3% compared with 38.1% in the H pylori-negative population (P < or = 0.05). There were no patients with H pylori in the youngest age group. In the second age group (1-10 years), 100% of the H pylori-positive patients had RE, whereas 44.6% of the H pylori-negative patients had RE (P < or = 0.05). Both male and female patients with H pylori had a higher prevalence of RE, 77.8% and 85.7%, respectively. On a multivariate logistical regression, for the overall study cohort, H pylori-positive patients had an odds ratio of 5.79 of developing RE compared with H pylori-negative patients (P < or = 0.05). CONCLUSIONS: Our study results indicate that there is a significantly higher prevalence of RE in an H pylori-infected cohort independent of age or sex. The findings suggest that H pylori infection in children is positively associated with RE.

Esophageal IgE, IgG4, and mucosal eosinophilia in individuals with dysphagia.

BACKGROUND: Eosinophilic esophagitis (EoE) is an inflammatory disease of the esophagus, producing failure to thrive in infants and dysphagia with food impaction in older children and adults. Although most people with EoE manifest atopic/allergic disease, the specific allergens to which immunoglobulin E (IgE) is directed, if any, have not yet been characterized. METHODS: Mucosal brush biopsy (MBB) and solid tissue biopsy (STB) specimens were prospectively obtained from 25 individuals with dysphagia and suspicion of EoE. Specific IgE (sIgE) against 112 epitopes from airborne and food proteins, antigens known to cause a polyclonal IgE response and IgG4 to food allergens, were measured. RESULTS: There was no difference in total IgE harvested between the 2 biopsy methods (p > 0.05) or between the EoE-positive (N = 12) and EoE-negative (N = 13) groups (p > 0.05). None of the samples in either group contained measurable serum IgE to any of the airborne or food proteins tested, but low levels of IgE specific to Candida and Staphylococcus enterotoxins were detected. Low levels of IgG4 specific to wheat, soy, peanut, and egg were also detected. CONCLUSIONS: Both MBB and STB are able to harvest measureable levels of IgE and IgG4 from the esophageal mucosa. Low levels of serum-specific IgE suggest that other inflammatory mechanisms, besides type I, IgE-mediated, allergen-specific hypersensitivity, may act as the primary catalyst for mucosal eosinophilia. Clarifying the role of both IgE-mediated and non-IgE-mediated inflammatory mechanisms will help identify more targeted diagnostic and treatment strategies for individuals who present with dysphagia and esophageal eosinophilia.

Magnetic resonance enterography and wireless capsule endoscopy in the evaluation of patients with inflammatory bowel disease.

BACKGROUND: Magnetic resonance enterography (MRE) is increasingly used in children due to growing concerns of radiation. OBJECTIVE: To determine the performance of MRE, imaging findings were compared to wireless capsule endoscopy (WCE) and histology results in children with/or suspected inflammatory bowel disease (IBD). MATERIALS AND METHODS: Pathology and WCE reports were retrospectively reviewed in 23 patients who had MRE. RESULTS: The sensitivity of MRE was 75.0% while the sensitivity of WCE was 77.8%. CONCLUSION: MRE and WCE are complementary techniques in evaluation of the small bowel in IBD.