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Background and Aims: PTEN hamartoma tumor syndrome (PHTS) confers a high risk of specific cancers and is the most common genetic cause of autism spectrum disorder (ASD). Gastrointestinal (GI) phenotypes in PHTS are poorly characterized in children. Thus, we aimed to characterize the GI and hepatic manifestations in children with PHTS and to investigate genotype-phenotype associations. Methods: We performed a retrospective chart review of prospectively accrued children with PHTS at 2 tertiary-care centers. Wilcoxon rank-sum, Chi-squared, and Fisher’s exact tests and Firth’s logistic regression were utilized to explore associations between variables. Results: This series included 80 children with disease-causing PTEN variants. Common GI manifestations included constipation in 41 (51%), feeding issues in 31 (39%), and polyps in 22 (28%) children. The polyps were of mixed histologic types. Eosinophilic gastrointestinal disorders were observed in 5 (6%) children. Crohn’s disease, celiac disease, and protein-losing enteropathy were observed once each. Eosinophilic gastrointestinal disorders were observed exclusively in patients without ASD (P = .052). Nonsense PTEN variants were enriched in those with polyps (P = .029). Missense PTEN variants (OR 2.9, P = .034) and upper GI polyps (OR 4.4, P = .018) were associated with increased odds of constipation. Conclusion: Constipation and feeding issues are common in children with PHTS. Polyps are more prevalent in children with PHTS than previously described and associated with nonsense PTEN variants. Children without ASD represent a distinct patient subset with a predisposition to eosinophilic gastrointestinal disorders and possibly upper GI polyps. Endoscopic evaluation should continue to be performed in symptomatic children with PHTS, with consideration of closer follow-up in those without ASD.

Colonoscopy is an important diagnostic and therapeutic tool in evaluating and treating gastrointestinal tract pathologies. Adequate visualization of the intestinal lumen is necessary for detection of lesions, and thus bowel preparation is a key component of the process. It is estimated that over 25% percent of pediatric patients have sub-optimal bowel preparations, which can lead to longer procedure times, missed pathology, unsuccessful ileal intubation, and possibly repeat procedure/anesthesia. There is no universal protocol for bowel preparation in pediatrics and there is a wide variability of practices around the world. The purpose of this paper is to review the recent published literature regarding bowel preparations for pediatric colonoscopy with focus on published work in the last decade exploring a number of factors involved in bowel preparation including the role of patient education, types of bowel preparation, and their efficacy and safety.

OBJECTIVES/SPECIFIC AIMS: Juvenile Polyposis Syndrome (JPS) is an inherited cancer predisposition syndrome sometimes attributed to a germline mutation in SMAD4 or BMPR1A. However, many patients meet clinical criteria for JPS without having a pathogenic alteration in either gene. Herein, we perform a cross-sectional analysis of JPS patients at a pediatric and adult tertiary referral center to understand potential differences in the clinical presentation and outcomes of patients with or without a known causative gene mutation. Additionally, we conduct whole exome sequencing (WES) on a subset of the pediatric patients to evaluate for novel genomic drivers of disease. METHODS/STUDY POPULATION: Data were abstracted from medical charts using IRB-approved protocols at the Children’s Hospital of Philadelphia (CHOP) and the University of Pennsylvania (Penn). Records were reviewed for patients with a clinical diagnosis of JPS and genetic testing result and seen at either institution in the last 10 years (2008-2018). Patients recruited for sequencing were consented for blood draw through the CHOP IRB protocol, and had whole exome sequencing completed at 70X depth, with data analyzed through institutional pipeline. RESULTS/ANTICIPATED RESULTS: Records were reviewed for 41 patients at CHOP and 19 patients at Penn, for a total of 60 JPS patients. Mean age of CHOP cohort was 11 years: 58.5% male, mean length of follow up 3.9 years. Mean age Penn cohort was 33 years: 47.4% male, mean length of follow up 9.3 years. In the pediatric cohort, 7 patients (17%) had a mutation in BMPR1A (n=6) or SMAD4 (n=1); in the adult cohort, 15 patients (79%) had a mutation in BMPR1A (n=3) or SMAD4 (n=12). The average number of polyps in the pediatric cohort was not significantly higher in patients with a SMAD4 or BMPR1A mutation (9.3 polyps/year of surveillance with a SMAD4 or BMPR1A mutation, vs 5.7 polyps/year; p=0.19). In combined cohort review, all individuals that required gastrectomy and/or colectomy (n=8) as well as all those who developed gastrointestinal cancer (n=3) had a mutation in SMAD4 or BMPR1A. Of the patients who underwent whole exome sequencing (n=13), potential causative germline mutations were identified in four patients (30.8%); all potential drivers identified were within the TNF/BMP pathway. DISCUSSION/SIGNIFICANCE OF IMPACT: This data from a dual-institution review demonstrates that the rate of SMAD4/BMPR1A mutation in JPS is lower in a pediatric cohort compared to an adult cohort. Furthermore, although individuals with JPS may have similar clinical presentations in childhood regardless of whether or not a causative mutation is present, the presence of a mutation in SMAD4 or BMPR1A is associated with a more severe course of disease in adulthood. Further study and a larger cohort will be required to fully validate these findings. Approximately 30% of patients who underwent germline WES had a potential novel driver identified, with further validation underway.

The aim of this paper was to determine the changes in viscosity of stirred yoghurt from producer A (n = 20) and producer B (n = 20) throughout 21 days of storage. The content of fat, dry matter, non-fat dry matter, lactic acid, pH and viscosity of stirred yoghurt were determined on the 0, 7th, 14th and the 21st day of storage of the product at the temperature of 4 °C. Considerable change in viscosity of stirred yoghurt (p < 0,05) throughout the maintenance period was determined on the 0 and the 21st day for both yoghurts. The viscosity of the stirred yoghurt from producer A was increased from 0,324Pa s on the 0 day to 1,912 Pa s on the 21st day. At the same time the viscosity of the stirred yoghurt from producer B was increased from 0,208 Pa s on the 0 day to 0,883 Pa s on the 21st day. In comparison with producer A, a considerably higher quantity of non-fat dry matter and higher quantities of lactic acid (p

OBJECTIVE:: The Pediatric Crohn''s Disease Activity Index (PCDAI) is a validated measure of disease activity comprised of historical, laboratory and physical examination parameters. It has been suggested that an abbreviated PCDAI may be of similar utility without requiring laboratory evaluations or calculated height velocity. The aim of this study was to compare an abbreviated PCDAI and the original PCDAI and also compare the abbreviated PCDAI and a quality-of-life measurement. METHODS:: The authors prospectively analyzed quality of life and disease activity, using the IMPACT-35 Questionnaire, the PCDAI and an abbreviated PCDAI consisting of three historical items (abdominal pain, stools and patient functioning) and three physical examination items (weight, abdomen and perirectal disease). RESULTS:: Forty subjects aged 5'''24 years (22 males) were included in analysis. Correlations were performed between the original PCDAI, an abbreviated PCDAI and the IMPACT-35. There was a significant, strong correlation between the PCDAI and the abbreviated PCDAI (n = 40, r = 0.849, p <0.001), a significant, moderate correlation between PCDAI and IMPACT-35 (n = 29, r = '''0.547, p = 0.002) and a significant, moderate correlation between the abbreviated PCDAI and IMPACT-35 (n = 29, r = '''0.579, p <0.001). CONCLUSIONS:: An abbreviated PCDAI predicted disease activity as well as the full PCDAI. The IMPACT-35 correlated well with disease activity based on both PCDAI and an abbreviated PCDAI. An abbreviated PCDAI may offer advantages over the original PCDAI and should be prospectively validated in future studies. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The role of infliximab in treating pediatric ulcerative colitis (UC) is not defined. The authors previously have described their experience with the open label use of infliximab in nine children with moderate to severe UC. The aim of this study was to describe the outcome of these patients after a minimum 2-year follow-up and to describe the responses of eight additional patients to this medication. METHODS: The authors reviewed all pediatric patients with UC who received infliximab at The Children's Hospital of Philadelphia from its first use until February 2003. Tolerance of the infusions and adverse events were recorded. RESULTS: Follow-up information for a minimum of 2 years was reviewed for the nine initial patients. A total of 73 infliximab infusions were administered to these patients. Seven of nine (78%) patients were considered to be responders to the initial dose of infliximab. Two of these patients became nonresponders within 9 months of the first dose of infliximab and underwent colectomy. Of the remaining five (56%) patients with sustained response, two continue to receive infliximab infusions and three are doing well without infliximab. One patient experienced an infusion reaction, and one experienced herpes zoster infection. We have treated eight additional UC patients with infliximab. Seven (88%) patients were considered responders. One responder experienced relapse within 2 months. Overall, a short-term improvement was seen in 14 of 17 (82%) patients, and sustained improvement in 10 of 16 (63%) patients followed up for more than 9 months. All five patients with severe or fulminant UC, unresponsive to 2 weeks of intravenous corticosteroid therapy, experienced improvement with infliximab. Infliximab was well tolerated. CONCLUSION: Infliximab is associated with short- and long-term clinical improvement in children and adolescents with moderate to severe UC. [ABSTRACT FROM AUTHOR]

BACKGROUND The site for percutaneous liver biopsy is determined by physical examination and anatomic landmarks. The authors compared physical examination with ultrasound examination to determine liver location, size, and an optimal biopsy site.METHODS A pediatric gastroenterology fellow or attending gastroenterologist initially selected a biopsy site by physical examination. An ultrasonographer performed a limited ultrasound examination to evaluate this site.RESULTS Sixty biopsy sites from 58 patients were evaluated. Forty-six patients had no previous liver surgery. Two patients had had a Kasai procedure. Ten patients had had orthotopic liver transplantation. The mean age of the patients was 11.1 ± 7.6 years. Ultrasonography detected the following potential complications of percutaneous biopsy at the site determined by physical examination: insufficient liver (7 of 15, 47.0%), diaphragm injury (4 of 15, 27.0%), bowel perforation (2 of 15, 13.0%), kidney laceration (1 of 15, 7.0%), and large blood vessel laceration (1 of 15, 7.0%). These ultrasound findings directed a change in biopsy site for 15 (25.0%) physical examination sites. Major biopsy complications were rare (1.7%).CONCLUSION Ultrasound examination resulted in a location change to a more optimal site in 25.0% of the sites determined by physical examination. Ultrasound determination of the biopsy site should be considered before pediatric percutaneous liver biopsy. [ABSTRACT FROM AUTHOR]