Background Entrustable Professional Activities (EPA) and competencies represent components of a competency-based education framework. EPAs are assessed based on the level of supervision (LOS) necessary to perform the activity safely and effectively. The broad competencies, broken down into narrower subcompetencies, are assessed using milestones, observable behaviors of one’s abilities along a developmental spectrum. Integration of the two methods, accomplished by mapping the most relevant subcompetencies to each EPA, may provide a cross check between the two forms of assessment and uncover those subcompetencies that have the greatest influence on the EPA assessment. Objectives We hypothesized that 1) there would be a strong correlation between EPA LOS ratings with the milestone levels for the subcompetencies mapped to the EPA; 2) some subcompetencies would be more critical in determining entrustment decisions than others, and 3) the correlation would be weaker if the analysis included only milestones reported to the Accreditation Council for Graduate Medical Education (ACGME). Methods In fall 2014 and spring 2015, the Subspecialty Pediatrics Investigator Network asked Clinical Competency Committees to assign milestone levels to each trainee enrolled in a pediatric fellowship for all subcompetencies mapped to 6 Common Pediatric Subspecialty EPAs as well as provide a rating for each EPA based upon a 5-point LOS scale. Results One-thousand forty fellows were assessed in fall and 1048 in spring, representing about 27% of all fellows. For each EPA and in both periods, the average milestone level was highly correlated with LOS (rho range 0.59–0.74; p < 0.001). Correlations were similar when using a weighted versus unweighted milestone score or using only the ACGME reported milestones (p > 0.05). Conclusions We found a strong relationship between milestone level and EPA LOS rating but no difference if the subcompetencies were weighted, or if only milestones reported to the ACGME were used. Our results suggest that representative behaviors needed to effectively perform the EPA, such as key subcompetencies and milestones, allow for future language adaptations while still supporting the current model of assessment. In addition, these data provide additional validity evidence for using these complementary tools in building a program of assessment.

Background: Gut microbiome dysbiosis has been demonstrated in subjects with newly diagnosed and chronic inflammatory bowel disease (IBD). In this study we sought to explore longitudinal changes in dysbiosis and ascertain associations between dysbiosis and markers of disease activity and treatment outcome. Methods: We performed a prospective cohort study of 19 treatment-naïve pediatric IBD subjects and 10 healthy controls, measuring fecal calprotectin and assessing the gut microbiome via repeated stool samples. Associations between clinical characteristics and the microbiome were tested using generalized estimating equations. Random forest classification was used to predict ultimate treatment response (presence of mucosal healing at follow-up colonoscopy) or non-response using patients' pretreatment samples. Results: Patients with Crohn's disease had increased markers of inflammation and dysbiosis compared to controls. Patients with ulcerative colitis had even higher inflammation and dysbiosis compared to those with Crohn's disease. For all cases, the gut microbial dysbiosis index associated significantly with clinical and biological measures of disease severity, but did not associate with treatment response. We found differences in specific gut microbiome genera between cases/controls and responders/non-responders including Akkermansia, Coprococcus, Fusobacterium, Veillonella, Faecalibacterium, and Adlercreutzia. Using pretreatment microbiome data in a weighted random forest classifier, we were able to obtain 76.5 % accuracy for prediction of responder status. Conclusions: Patient dysbiosis improved over time but persisted even among those who responded to treatment and achieved mucosal healing. Although dysbiosis index was not significantly different between responders and non-responders, we found specific genus-level differences. We found that pretreatment microbiome signatures are a promising avenue for prediction of remission and response to treatment.

Objectives: Fellowship program directors (FPD) and Clinical Competency Committees (CCCs) both assess fellow performance. We examined the association of entrustment levels determined by the FPD with those of the CCC for 6 common pediatric subspecialty entrustable professional activities (EPAs), hypothesizing there would be strong correlation and minimal bias between these raters. Methods: The FPDs and CCCs separately assigned a level of supervision to each of their fellows for 6 common pediatric subspecialty EPAs. For each EPA, we determined the correlation between FPD and CCC assessments and calculated bias as CCC minus FPD values for when the FPD was or was not a member of the CCC. In addition, we examined the effect of program size, FPD understanding of EPAs, and subspecialty on the correlations. Data were obtained in fall 2014 and spring 2015. Results: A total of 1040 fellows were assessed in the fall and 1048 in the spring. In both periods and for each EPA, there was a strong correlation between FPD and CCC supervision levels (P < .001). The correlation was somewhat lower when the FPD was not a CCC member (P < .001). Overall bias in both periods was small. Conclusions: The correlation between FPD and CCC assignment of EPA supervision levels is strong. Although slightly weaker when the FPD is not a CCC member, bias is small, so this is likely unimportant in determining fellow entrustment level. The similar performance ratings of FPDs and CCCs support the validity argument for EPAs as competency-based assessment tools.

Backgrounds: Recent studies have identified the role of serologic markers in characterizing disease phenotype, location, complications, and severity among Northern Europeans (NE) with Crohn's disease (CD). However, very little is known about the role of serology in CD among African Americans (AA). Our study explored the relationship between serology and disease phenotype in AA with CD, while controlling for genetic ancestry. Methods: AAs with CD were enrolled as participants through multicenter collaborative efforts. Serological levels of IgA anti-Saccharomyces cervisiae antibody (ASCA), IgG ASCA, E. coli outermembrane porin C, anti-CBir1, and ANCA were measured using enzyme-linked immunosorbent assays. Genotyping was performed using Illumina immunochip technology; an admixture rate was calculated for each subject. Multiple imputation by chained equations was performed to account for data missing at random. Logistic regression was used to calculate adjusted odds ratio (OR) for associations between serological markers and both complicated disease and disease requiring surgery. Results: A total of 358 patients were included in the analysis. The majority of our patients had inflammatory, noncomplicated disease (58.4%), perianal disease (55.7%), and documented colonic inflammation (86.8%). On multivariable analysis, both IgG ASCA and OmpC were associated with complicated disease (OR, 2.67; 95% CI, 1.67-4.28; OR, 2.23; 95% CI, 1.41-3.53, respectively) and disease requiring surgery (OR, 2.51; 95% CI, 1.49-4.22; OR, 3.57; 95% CI, 2.12-6.00). NE admixture to the African genome did not have any associations or interactions in relation to clinical outcome. Conclusions: Our study comprises the largest cohort of AAs with CD. The utility of serological markers for the prognosis of CD in NE applies equally to AA populations.

Background Crohn’s disease (CD) is highly heritable. NOD2 has emerged as the main susceptibility gene among individuals of European ancestry; however, NOD2 does not appear to contribute to CD susceptibility among many non-European populations. Today’s African American (AA) population represents an admixture of West African (80%) and European (20%) ancestry. Since genotype-based tools are becoming increasingly available for CD, it is important that we validate the risk variants in different populations, such as admixed AAs. Methods We analyzed the NOD2 variants among admixed AAs (n=321, 240 with CD and 111 healthy controls) and non-admixed West Africans (n=40) by genotyping for 4 known disease-causing NOD variants. We extracted the publically available 1000 Genomes data on NOD2 variants from 500 subjects of West African origin. Association with disease was evaluated by logistic regression. Results An association with CD was found for the classical SNP 1007fs (2.6% CD, 0% HC, p=0.012); there was no association when the genotypic and allelic frequencies of the risk alleles were compared for SNPs R702W and G908R. No known NOD2 risk alleles were seen in either the West African cohort or in subjects of African ancestry from the 1000 Genomes project. Conclusions The NOD2 gene is a risk for CD in AAs, although the allele frequencies and the attributable risk are much lower compared to Caucasians. The risk alleles are not seen in the West African population suggesting the risk for CD contributed by NOD2 among AAs is due exclusively to recent European admixture

Background: Lack of evidence-based outcomes data leads to uncertainty in developing treatment regimens in children who are newly diagnosed with ulcerative colitis. We hypothesised that pretreatment clinical, transcriptomic, and microbial factors predict disease course. Methods: In this inception cohort study, we recruited paediatric patients aged 4–17 years with newly diagnosed ulcerative colitis from 29 centres in the USA and Canada. Patients initially received standardised mesalazine or corticosteroids, with pre-established criteria for escalation to immunomodulators (ie, thiopurines) or anti-tumor necrosis factor-α (TNFα) therapy. We used RNA sequencing to define rectal gene expression before treatment, and 16S sequencing to characterise rectal and faecal microbiota. The primary outcome was week 52 corticosteroid-free remission with no therapy beyond mesalazine. We assessed factors associated with the primary outcome using logistic regression models of the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01536535. Findings: Between July 10, 2012, and April 21, 2015, of 467 patients recruited, 428 started medical therapy, of whom 400 (93%) were evaluable at 52 weeks and 386 (90%) completed the study period with no protocol violations. 150 (38%) of 400 participants achieved week 52 corticosteroid-free remission, of whom 147 (98%) were taking mesalazine and three (2%) were taking no medication. 74 (19%) of 400 were escalated to immunomodulators alone, 123 (31%) anti-TNFα therapy, and 25 (6%) colectomy. Low baseline clinical severity, high baseline haemoglobin, and week 4 clinical remission were associated with achieving week 52 corticosteroid-free remission (n=386, logistic model area under the curve [AUC] 0·70, 95% CI 0·65–0·75; specificity 77%, 95% CI 71–82). Baseline severity and remission by week 4 were validated in an independent cohort of 274 paediatric patients with newly diagnosed ulcerative colitis. After adjusting for clinical predictors, an antimicrobial peptide gene signature (odds ratio [OR] 0·57, 95% CI 0·39–0·81; p=0·002) and abundance of Ruminococcaceae (OR 1·43, 1·02–2·00; p=0·04), and Sutterella (OR 0·81, 0·65–1·00; p=0·05) were independently associated with week 52 corticosteroid-free remission. Interpretation: Our findings support the utility of initial clinical activity and treatment response by 4 weeks to predict week 52 corticosteroid-free remission with mesalazine alone in children who are newly diagnosed with ulcerative colitis. The development of personalised clinical and biological signatures holds the promise of informing ulcerative colitis therapeutic decisions. Funding: US National Institutes of Health.

Hereditary hemorrhagic telangiectasia (HHT) is an underreported autosomal dominant vascular dysplasia. Neonatal presentations of HHT are rare, as this disorder typically presents in adolescence or beyond with epistaxis. We report a female neonate with hematochezia on the 1st day of life secondary to multiple gastrointestinal arteriovenous malformations (AVMs) along with intracranial hemorrhage. We describe her clinical course and management, as well as her novel family mutation in ENG. This is the first reported HHT case with significant gastrointestinal bleeding in the newborn. We review neonatal HHT and raise the consideration for more directed prenatal imaging and delivery options for fetuses at high risk of HHT.

Background/Objectives:Esophageal button battery impactions (BBI) in children pose a significant danger to children. Although there are expert-opinion guidelines to help manage this population, few studies detail the impact of guidelines on the clinical care of these patients. With this study, we aimed to describe the care of these patients before and following adoption of guidelines at a single center.Methods:Retrospective cohort study of patients with esophageal BBI at a single center, large volume, urban academic pediatric hospital system before adoption of expert-opinion guidelines (2007-2017) and following adoption (2018-2020).Results:Cohort was comprised of 31 patients before adoption and 32 patients following adoption of guidelines. Patient characteristics did not differ between groups. After 2018, significantly more patients received acetic acid irrigation, initial cross-sectional imaging, and serial cross-sectional imaging. There was also an increase in intensive care unit (ICU) stays, number of intubations, nil per os time, and hospital length of stay. There was no difference in patient outcomes.Conclusion:This study describes a large cohort of pediatric esophageal BBI before and following adoption of guidelines. Findings detail increased adherence to guidelines resulting in more cross-sectional imaging which led to ICU stays, longer length of stays, and more nil per os time. This study emphasizes the need for multi-disciplinary guidelines as well as further multi-institutional study.

Objective Leptin was discovered in 1994 as a hormone produced by adipose tissue with a modulatory effect on feeding behavior and weight control. Recently, the stomach has been identified as an important source of leptin and growing evidence has shown diverse functions for leptin in the gastrointestinal tract. Methods Using leptin as a keyword in PubMed, more than 17 000 articles were identified, of which more than 500 articles were related to the role of leptin in the gastrointestinal tract. Available abstracts were reviewed and more than 200 original articles were reviewed in detail. Results The available literature demonstrated that leptin can modulate several important functions of the gastrointestinal tract. Leptin interacts with the vagus nerve and cholecystokinin to delay gastric emptying and has a complex effect on motility of the small bowel. Leptin modulates absorption of macronutrients in the gastrointestinal tract differentially in physiologic and pathologic states. In physiologic states, exogenous leptin has been shown to decrease carbohydrate absorption and to increase the absorption of small peptides by the PepT1 di-/tripeptide transporter. In certain pathologic states, leptin has been shown to increase absorption of carbohydrates, proteins, and fat. Leptin has been shown to be upregulated in the colonic mucosa in patients with inflammatory bowel disease. Leptin stimulates gut mucosal cell proliferation and inhibits apoptosis. These functions have led to speculation about the role of leptin in tumorigenesis in the gastrointestinal tract, which is complicated by the multiple immunoregulatory effects of leptin. Conclusion Leptin is an important modulator of major aspects of gastrointestinal tract functions, independent of its more well-described roles in appetite regulation and obesity.

BACKGROUND:: Vitamin D deficiency and low bone mineral density (BMD) are complications of inflammatory bowel disease. Vitamin D deficiency is more prevalent among African Americans compared with whites. There are little data comparing differences in serum 25-hydroxyvitamin D (25OHD) concentrations and BMD between African American and white children with Crohn disease (CD). METHODS:: We compared serum 25OHD concentrations of African American children with CD (n=52) to white children with CD (n=64) and healthy African American controls (n=40). We also analyzed BMD using dual-energy x-ray absorptiometry results from our pediatric CD population. RESULTS:: African American children with CD had lower serum 25OHD concentrations (16.1 [95% confidence interval, CI 14.5-17.9] ng/mL) than whites with CD (22.3 [95% CI 20.2-24.6] ng/mL; P<0.001). African Americans with CD and controls exhibited similar serum 25OHD concentration (16.1 [95% CI 14.5-17.9] vs 16.3 [95% CI 14.4-18.4] ng/mL; NS). African Americans with CD exhibited no difference in serum 25OHD concentration when controlling for seasonality, disease severity, and surgical history, although serum 25OHD concentration was significantly decreased in overweight children (body mass index ≥85%, P=0.003). Multiple regression analysis demonstrated that obese African American girls with CD had the lowest serum 25OHD concentrations (9.6 [95% CI 6.8-13.5] ng/mL). BMD was comparable between African American and white children with CD (z score -0.4±0.9 vs -0.7±1.2; NS). CONCLUSIONS:: African American children with CD are more likely to have vitamin D deficiency compared with white children with CD, but have similar BMD. CD disease severity and history of surgery do not affect serum 25OHD concentrations among African American children with CD. African American children have low serum 25OHD concentrations, independent of CD, compared with white children. Future research should focus on how race affects vitamin D status and BMD in children with CD.