Implementing Entrustable Professional Activities in Pediatric Fellowships: Facilitating the Process.

BACKGROUND AND OBJECTIVES: Entrustable professional activities (EPAs) will be used for initial certification by the American Board of Pediatrics by 2028. Less than half of pediatric fellowships currently use EPAs for assessment, yet all will need to adopt them. Our objectives were to identify facilitators and barriers to the implementation of EPAs to assess pediatric fellows and to determine fellowship program directors' (FPD) perceptions of EPAs and Milestones. METHODS: We conducted a survey of FPDs from 15 pediatric subspecialties. EPA users were asked about their implementation of EPAs, barriers encountered, and perceptions of EPAs. Nonusers were queried about deterrents to using EPAs. Both groups were asked about potential facilitators of implementation and their perceptions of Milestones. RESULTS: The response rate was 65% (575/883). Of these, 344 (59.8%) were EPA users and 231 (40.2%) were nonusers. Both groups indicated work burden as a barrier to implementation. Nonusers reported more barriers than users (mean [SD]: 7 [3.8] vs 5.8 [3.4], P < .001). Both groups identified training materials and premade assessment forms as facilitators to implementation. Users felt that EPAs were easier to understand than Milestones (89%) and better reflected what it meant to be a practicing subspecialty physician (90%). In contrast, nonusers felt that Milestones were easy to understand (57%) and reflected what it meant to be a practicing subspecialist (58%). CONCLUSIONS: Implementing EPA-based assessment will require a substantial investment by FPDs, facilitated by guidance and easily accessible resources provided by multiple organizations. Perceived barriers to be addressed include FPD time constraints, a need for additional assessment tools, and outcomes data.

Pediatric Gastrointestinal Histopathology in Patients With Tetratricopeptide Repeat Domain 7A (TTC7A) Germline Mutations: A Rare Condition Leading to Multiple Intestinal Atresias, Severe Combined Immunodeficiency, and Congenital Enteropathy.

Mutations in the tetratricopeptide repeat domain 7A (TTC7A) gene are a rare cause of congenital enteropathy that can result in significant morbidity. TTC7A deficiency leads to disruption of the intestinal epithelium. The histopathology of this condition has been partly described in case reports and clinical studies. This manuscript describes an in-depth investigation of the pediatric gastrointestinal pathology of the largest histologically examined cohort with confirmed TTC7A mutations reported to date and, for the first time, compared the findings to age-matched and sex-matched control patients with intestinal atresia not thought to be associated with TTC7A mutations. Hematoxylin and eosin-stained slides of endoscopically obtained mucosal biopsies and surgical resection specimens from 7 patients with known TTC7A mutations were examined retrospectively. The microscopic findings were found to be on a spectrum from atresia-predominant to those with predominantly epithelial abnormalities. Several unique histopathologic characteristics were observed when compared with controls. These included neutrophilic colitis and prominent lamina propria eosinophilia throughout the gastrointestinal tract. Striking architectural abnormalities of the epithelium were observed in 4 of the 7 patients. The 5 patients with intestinal atresia demonstrated hypertrophy and disorganization of the colonic muscularis mucosae accompanied by bland spindle cell nodules within the intestinal wall. The components of the latter were further elucidated using immunohistochemistry, and we subsequently hypothesize that they represent obliterated mucosa with remnants of the muscularis mucosae. Finally, atrophic gastritis was noted in 4 patients. In conclusion, the unique histopathologic characteristics of TTC7A mutation-associated enteropathy described herein more fully describe this novel disease entity in infants who present with congenital enteropathy or enterocolitis.

The Student-Generated Reasoning Tool (SGRT): Linking medical knowledge and clinical reasoning in preclinical education.

INTRODUCTION: The simultaneous integration of knowledge acquisition and development of clinical reasoning in preclinical medical education remains a challenge. To help address this challenge, the authors developed and implemented the Student-Generated Reasoning Tool (SGRT)-a tool asking students to propose and justify pathophysiological hypotheses, generate findings, and critically appraise information. METHODS: In 2019, students in a first-year preclinical course (n = 171; SGRT group) were assigned to one of 20 teams. Students used the SGRT individually, then in teams, and faculty provided feedback. The control group (n = 168) consisted of students from 2018 who did not use SGRT. Outcomes included academic performance, effectiveness of collaborative environments using the SGRT, and student feedback. RESULTS: Students were five times more likely to get questions correct if they were in the SGRT group versus control group. Accuracy of pathophysiological hypotheses was significantly lower for individuals than teams. Qualitative analysis indicated students benefited from generating their own data, justifying their reasoning, and working individually as well as in teams. CONCLUSIONS: This study introduces the SGRT as a potentially engaging, case-based, and collaborative learning method that may help preclinical medical students become aware of their knowledge gaps and integrate their knowledge in basic and clinical sciences in the context of clinical reasoning.

A Case of Red Retching?

This piece features a 14-year-old young man who presented with epigastric pain and bright red emesis. His father brought both a photo and sample of the vomitus, which guided initial management in one direction, and then on closer inspection, diverted his diagnostic trajectory. Through a traditional case report and accompanied image and prose, we explore how we process and reinterpret visual data to help guide our management of hematemesis.

Understanding and Optimizing Group Dynamics in Case-Based Collaborative Learning.

Teamwork skills are recognized as a core competency of physicians. To more effectively prepare trainees for the demands of their future work, medical educators are increasingly turning to group-based instructional formats. We employ case-based collaborative learning (CBCL) - a format which requires daily in-class discussion and collaboration in assigned small groups. While students overwhelmingly embraced CBCL as stimulating and thought-provoking, some students reported that social dynamics among group members adversely impacted their experience. Using mixed methods, we demonstrate that a short intervention that asked students to discuss how they can best learn together improved small group dynamics, and promoted psychological safety among peers. Importantly, no specific instruction in team work was required, students overall had a clear understanding how they could improve, but they did not know how to start this conversation with each other. To promote team learning, we propose that educators emphasize students' accountability to their peers' learning in addition to their own, and devote some time in class for teams to reflect and discuss how to improve learning with each other. Our observations are of interest to anyone frequently relying on group work without peer assessment or formal feedback on group performance.

Variable management strategies for NEC totalis: a national survey.

BACKGROUND/OBJECTIVES: Necrotizing enterocolitis (NEC) is a serious disease linked to prematurity. A variant, NEC totalis, is associated with nearly 100% mortality. There is wide variation in counseling practices for NEC totalis. Our objectives are to determine what treatment options, if any, are offered to families, and which factors influence these decisions. METHODS: An anonymous survey was distributed to members of the AAP Sections on Neonatal-Perinatal Medicine and Pediatric Surgery. Data were analyzed utilizing chi-square tests and Spearman correlations, where applicable. RESULTS: In the setting of NEC totalis, 90% of the 378 respondents viewed offering life-sustaining interventions (LSI) as ethically permissible and 87% felt that transfer to another center willing to provide LSI should be considered; however, only 43% reported offering LSI to families. CONCLUSIONS: Management of NEC totalis remains challenging and significant practice variability persists. Most respondents do not offer ongoing medical/surgical management, despite believing it is an ethically permissible option.

Neonatal-Onset Chronic Diarrhea Caused by Homozygous Nonsense WNT2B Mutations.

Homozygous nonsense mutations in WNT2B were identified in three individuals from two unrelated families with severe, neonatal-onset osmotic diarrhea after whole-exome sequencing was performed on trios from the two families. Intestinal biopsy samples from affected individuals were used for histology and immunofluorescence and to generate enteroids ex vivo. Histopathologic evaluation demonstrated chronic inflammatory changes in the stomach, duodenum, and colon. Immunofluorescence demonstrated diminished staining for OLFM4, a marker for intestinal stem cells (ISCs). The enteroids generated from WNT2B-deficient intestinal epithelium could not be expanded and did not survive passage. Addition of CHIR-99021 (a GSK3A and GSK3B inhibitor and activator of canonical WNT/ß-CATENIN signaling) could not rescue WNT2B-deficient enteroids. Addition of supplemental recombinant murine WNT2B was able to perpetuate small enteroids for multiple passages but failed to expand their number. Enteroids showed a 10-fold increase in the expression of LEF1 mRNA and a 100-fold reduction in TLR4 expression, compared with controls by quantitative RT-PCR, indicating alterations in canonical WNT and microbial pattern-recognition signaling. In summary, individuals with homozygous nonsense mutations in WNT2B demonstrate severe intestinal dysregulation associated with decreased ISC number and function, likely explaining their diarrheal phenotype. WNT2B deficiency should be considered for individuals with neonatal-onset diarrhea.

Advances in Evaluation of Chronic Diarrhea in Infants.

Diarrhea is common in infants (children less than 2 years of age), usually acute, and, if chronic, commonly caused by allergies and occasionally by infectious agents. Congenital diarrheas and enteropathies (CODEs) are rare causes of devastating chronic diarrhea in infants. Evaluation of CODEs is a lengthy process and infrequently leads to a clear diagnosis. However, genomic analyses and the development of model systems have increased our understanding of CODE pathogenesis. With these advances, a new diagnostic approach is needed. We propose a revised approach to determine causes of diarrhea in infants, including CODEs, based on stool analysis, histologic features, responses to dietary modifications, and genetic tests. After exclusion of common causes of diarrhea in infants, the evaluation proceeds through analyses of stool characteristics (watery, fatty, or bloody) and histologic features, such as the villus to crypt ratio in intestinal biopsies. Infants with CODEs resulting from defects in digestion, absorption, transport of nutrients and electrolytes, or enteroendocrine cell development or function have normal villi to crypt ratios; defects in enterocyte structure or immune-mediated conditions result in an abnormal villus to crypt ratios and morphology. Whole-exome and genome sequencing in the early stages of evaluation can reduce the time required for a definitive diagnosis of CODEs, or lead to identification of new variants associated with these enteropathies. The functional effects of gene mutations can be analyzed in model systems such as enteroids or induced pluripotent stem cells and are facilitated by recent advances in gene editing procedures. Characterization and investigation of new CODE disorders will improve management of patients and advance our understanding of epithelial cells and other cells in the intestinal mucosa.

Unpasteurized Shared Human Milk Use in Pediatric Inpatients: Health and Ethical Implications.

Growing evidence supporting the health benefits of human milk, particularly in the preterm population, has led to rising demand for donor human milk in NICUs and pediatric hospitals. There are no previous reports describing the use of unpasteurized shared human milk (USHM) in the hospital setting, but the use of USHM solicited from community donors through social networks appears to be common. Many pediatric hospitals permit inpatients to receive breast milk that has been screened and pasteurized by a human milk banking organization and will provide pasteurized donor human milk (PDHM) only to infants who are preterm or have specific medical conditions. These policies are designed to minimize potential adverse effects from improperly handled or screened donor milk and to target patients who would experience the greatest benefit in health outcomes with donor milk use. We explore the ethical and health implications of 2 cases of medically complex infants who did not meet criteria in our tertiary care hospital for the use of PDHM from a regulated human milk bank and were incidentally found to be using USHM. These cases raise questions about how best to balance the ethical principles of beneficence, nonmaleficence, justice, and patient autonomy in the provision of PDHM, a limited resource. Health care staff should ask about USHM use to provide adequate counseling about the risks and benefits of various feeding options in the context of an infant's medical condition.

Identification and characterization of a novel DGAT1 missense mutation associated with congenital diarrhea.

Acyl-CoA:diacylglycerol acyltransferase (DGAT)1 and DGAT2 catalyze triglyceride (TG) biosynthesis in humans. Biallelic loss-of-function mutations in human DGAT1 result in severe congenital diarrhea and protein-losing enteropathy. Additionally, pharmacologic inhibition of DGAT1 led to dose-related diarrhea in human clinical trials. Here we identify a previously unknown DGAT1 mutation in identical twins of South Asian descent. These male patients developed watery diarrhea shortly after birth, with protein-losing enteropathy and failure to thrive. Exome sequencing revealed a homozygous recessive mutation in DGAT1, c.314T>C, p.L105P. We show here that the p.L105P DGAT1 enzyme produced from the mutant allele is less abundant, resulting in partial loss of TG synthesis activity and decreased formation of lipid droplets in patient-derived primary dermal fibroblasts. Thus, in contrast with complete loss-of-function alleles of DGAT1, the p.L105P missense allele partially reduces TG synthesis activity and causes a less severe clinical phenotype. Our findings add to the growing recognition of DGAT1 deficiency as a cause of congenital diarrhea with protein-losing enteropathy and indicate that DGAT1 mutations result in a spectrum of diseases.

The Case-Based Collaborative Learning Peer Observation Worksheet and Compendium: An Evaluation Tool for Flipped Classroom Facilitators.

INTRODUCTION: In a flipped classroom, students learn basic concepts before class, allowing them time during class to apply newly gained knowledge to problem sets and cases. Harvard Medical School (HMS) has introduced a form of flipped classroom, called case-based collaborative learning (CBCL), during preclinical curricula. Finding few published resources, the HMS Academy's Peer Observation of Teaching Interest Group developed a guide for observations and feedback to CBCL facilitators. METHODS: After conducting an extensive literature search, speaking to flipped classroom methodology experts, and observing 14 facilitators using CBCL methods, the interest group identified specific teaching behaviors that optimize student interaction and knowledge application. The group next engaged in several rounds of the modified Delphi method to develop the CBCL peer observation worksheet and compendium and then tested these materials' effectiveness in capturing CBCL teaching behaviors and providing feedback to CBCL faculty facilitators. RESULTS: Seventy-three percent of faculty rated the worksheet and compendium as extremely helpful or helpful in identifying new teaching techniques. Moreover, 90% found the CBCL peer observation and debriefing to be extremely helpful or helpful, and 90% were extremely likely or likely to incorporate peer suggestions in future teaching sessions. DISCUSSION: Medical schools have begun to embrace flipped classroom methods to eliminate passive, lecture-style instruction during the preclinical years of the MD curriculum. This tool identifies specific in-classroom approaches that engage students in active learning, guides peer observers in offering targeted feedback to faculty on teaching strategies, and presents consensus-based resources for use during CBCL faculty development and training.

Pediatric non-Helicobacter pylori atrophic gastritis: a case series.

Although autoimmune atrophic gastritis is classically a disease of elderly adults, recent studies have described the disease in younger adults, particularly in those with other autoimmune diseases and iron-deficiency anemia. Atrophic gastritis in pediatrics is a rare and possibly underdiagnosed entity that has been primarily reported as single-case reports. This retrospective study of atrophic gastritis not associated with Helicobacter pylori infection was performed to further expand the knowledge of clinical presentation, pathologic findings, and natural history of this disease in the pediatric population. Twelve patients with a histologic diagnosis of atrophic gastritis were identified, with an age range of 8 months to 18 years. Seven had other autoimmune diseases and/or immunodeficiency. Atrophy was confined to the oxyntic mucosa in 10 patients, with intramucosal inflammation in a diffuse or basal-predominant pattern. Active inflammation was present in 7 patients. Pseudopyloric, intestinal, or squamous/mucinous metaplasia was seen at initial biopsy or on follow-up in 8 patients, and enterochromaffin-like cell hyperplasia was seen in 5. One patient developed an adenocarcinoma during the follow-up period of 10 years. Two false-negative diagnoses were retrospectively identified. In the majority of cases, the possibility of atrophic gastritis was not raised by the submitting physician, and the endoscopic findings were not specific. Therefore, accurate diagnosis requires a high degree of suspicion on the part of the pathologist, and the diagnosis should be considered particularly in patients with a clinical history of other autoimmune diseases or iron-deficiency anemia.

Embolization of a bleeding Dieulafoy lesion of the duodenum in a child. Case report and review of the literature.

We report an adolescent with chronic, recurrent upper gastrointestinal bleeding in whom extensive prior investigations failed to reveal the source of bleeding. Angiography accurately identified a bleeding Dieulafoy lesion of the duodenum which was successfully embolized. The clinical history, angiographic appearances and treatment of this rare lesion are presented.

Risk factors for small bowel bacterial overgrowth and diagnostic yield of duodenal aspirates in children with intestinal failure: a retrospective review.

BACKGROUND: Children with intestinal failure (IF) are at risk for small bowel bacterial overgrowth (SBBO) because of anatomical and other factors. We sought to identify risk factors for SBBO confirmed by quantitative duodenal culture. METHODS: A single-center retrospective record review of children who had undergone endoscopic evaluation for SBBO (defined as bacterial growth in duodenal fluid of >10(5) colony-forming unit per mL) was performed. RESULTS: We reviewed 57 children with median (25th-75th percentile) age 5.0 (2.0-9.2) years. Diagnoses included motility disorders (28%), necrotizing enterocolitis (16%), atresias (16%), gastroschisis (14%), and Hirschsprung disease (10.5%). Forty patients (70%) had confirmed SBBO. Univariate analysis showed no significant differences between patients with and without SBBO for the following variables: age, sex, diagnosis, presence of ileocecal valve, and antacid use. Patients receiving parenteral nutrition (PN) were more likely to have SBBO (70% vs 35%, P = .02). Multiple logistic regression analysis confirmed that PN administration was independently associated with SBBO (adjusted odds ratio, 5.1; adjusted 95% confidence interval, 1.4-18.3; P = .01). SBBO was not related to subsequent risk of catheter-related bloodstream infection (CRBSI). CONCLUSION: SBBO is strongly and independently associated with PN use. Larger prospective cohorts and more systematic sampling techniques are needed to better determine the relationship between SBBO and gastrointestinal function.

Cisapride improves enteral tolerance in pediatric short-bowel syndrome with dysmotility.

BACKGROUND AND OBJECTIVES: Gastrointestinal dysmotility is common in pediatric short-bowel syndrome, leading to prolonged parenteral nutrition dependence. There is limited literature regarding the safety and efficacy of cisapride for this indication. The aim of the study was to describe the safety and efficacy of cisapride for enteral intolerance in pediatric short-bowel syndrome. METHODS: Open-labeled pilot study in a limited access program for cisapride. Indications were short-bowel syndrome with underlying dysmotility and difficulty advancing enteral feeds despite standard therapies and without evidence of anatomic obstruction. Patients received cisapride 0.1 to 0.2 mg/kg per dose for 3 to 4 doses per day. We collected electrocardiogram, nutrition, and anthropometric data prospectively at study visits. RESULTS: Ten patients with mean (SD) age of 30.3 (30.5) months were enrolled in our multidisciplinary pediatric intestinal rehabilitation program. Median (interquartile range [IQR]) duration of follow-up was 8.7 (3.1-14.3) months. Median (IQR) residual bowel length was 102 (85-130) cm. Median (IQR) citrulline level was 14.5 (10.5-31.3) µmol/L. Diagnoses included isolated gastroschisis (n = 3), gastroschisis with intestinal atresia (n = 4), necrotizing enterocolitis (n = 2), and long-segment Hirschsprung disease (n = 1). Six subjects had at least 1 prior bowel-lengthening procedure. Median (IQR) change in percentage enteral energy intake was 19.9% (15.4%-29.8%) during follow-up (P = 0.01). Seven patients improved in enteral tolerance during treatment and 2 were weaned completely from parenteral nutrition. Complications during therapy were prolonged corrected QT interval (n = 2), gastrointestinal bleeding (n = 2), D-lactic acidosis (n = 1), and death due to presumed sepsis (n = 1). Longitudinal analysis (general estimating equation model) showed a strong positive association between cisapride duration and improved enteral tolerance. Mean percentage of enteral intake increased by 2.9% for every month of cisapride treatment (P < 0.0001). CONCLUSIONS: Cisapride is a potentially useful therapy in patients with pediatric short-bowel syndrome with gastrointestinal dysmotility. We observed modest improvement in feeding tolerance where prior treatments failed; however, patients treated with cisapride require careful cardiac monitoring because corrected QT prolongation occurred in 20% of our cohort.

Hypertrophic osteoarthropathy in intestinal transplant recipients.

We report 3 patients with periosteal new bone formation consistent with hypertrophic osteoarthropathy (HOA), in the context of intestinal allograft rejection. Patient 1 developed thick periosteal new bone formation of the right arm during a prolonged episode of intestinal acute cellular rejection (ACR) 2 months posttransplant. Patient 2 developed ankle pain and swelling during an episode of severe ACR. Plain films showed periosteal new bone formation of the left ankle. In patient 3, the right wrist became swollen during an episode of moderate ACR, whereas plain films demonstrated mild periosteal reaction. Patients 2 and 3 had resolution of their symptoms once the ACR resolved with treatment. This is the first case series of HOA occurring in association with intestinal ACR. We speculate that an immune-mediated process is responsible for the bone disease. Further inquiry will help establish if HOA is related to transplant status, intestinal inflammation, or allograft rejection in general.