Endoscopic and histologic utility of transnasal endoscopy in pediatric eosinophilic esophagitis.

Unsedated transnasal endoscopy (TNE) is an alternative method of examining the esophageal mucosa in pediatric patients with eosinophilic esophagitis (EoE), reducing cost, time, and risk associated with frequent surveillance esophagogastroduodenoscopies (EGD). Adequacy of transnasal esophageal biopsies for the evaluation of eosinophilic esophagitis histologic scoring system (EoEHSS) has not yet been evaluated. We compared procedure times, endoscopic findings, and EoEHSS scoring for EoE patients undergoing TNE versus standard EGD. Sixty-six TNE patients and 132 EGD controls matched for age (mean age 14.0 years) and disease status (29.3% active) were included. Compared to patients undergoing standard EGD, patients undergoing TNE spent 1.94 h less in the GI suite (p < 0.0001), with comparable occurrence rates of all visual endoscopic findings and most EoEHSS components. TNE serves as a useful tool for long-term disease surveillance, and consideration should be given to its use in clinical trials for EoE.

Canakinumab for the treatment of autoinflammatory very early onset- inflammatory bowel disease.

Introduction: Therapeutic options are critically needed for children with refractory very early onset inflammatory bowel disease (VEO-IBD). Our aim was to evaluate clinical response to canakinumab, an anti-IL-1ß monoclonal antibody, in patients with VEO-IBD whose phenotype resembles those with monogenic autoinflammatory disease. Methods: This is a single center retrospective study of patients with VEO-IBD with autoinflammatory phenotype (AIP) in the absence of identified monogenic disease treated with canakinumab for >6 months. AIP was defined as confirmed IBD with associated signs of systemic inflammation in the absence of infection, including leukocytosis, markedly elevated inflammatory markers, and extraintestinal manifestations (recurrent fevers, oral ulcers, arthritis). Primary outcomes included clinical response in disease activity indices after 6 months of therapy. Secondary outcomes included rate of AIP signs and symptoms, growth, surgery, steroid use, hospitalizations, and adverse events. Results: Nineteen patients were included: 47% with infantile onset, 58% classified as IBD-U, and 42% classified as CD. At baseline, 37% were biologic naïve, and canakinumab was used as dual therapy in 74% of patients. Clinical response was achieved in 89% with statistically significant improvement in PCDAI and PUCAI. Clinical remission was achieved in 32% of patients. There was significant improvement in the clinical manifestations of AIP and the biochemical markers of disease. Number of hospitalizations (p<0.01) and length of stay (p<0.05) decreased. Growth improved with median weight-for-length Z-score increasing from -1.01 to 1.1 in children less than 2 years old. There were minimal adverse events identified during the study period. Conclusion: Canakinumab may be an effective and safe treatment for a subset of children with VEO-IBD with AIP, as well as older patients with IBD. This study highlights the importance of a precision medicine approach in children with VEO-IBD.

Management of Magnet Ingestions at a Large Tertiary Care Children's Hospital.

OBJECTIVES: To review the clinical management and outcomes of magnet ingestions at a large tertiary children's hospital. To determine the association of frequency of high-powered magnet ingestion with the regulation of these magnets. METHODS: Children <18 years who presented to the emergency room and were admitted to the Children's Hospital of Philadelphia for ingestion of single or multiple magnets from January 2008 to December 2020 were included. Demographics, symptoms, management, and outcomes were analyzed. The frequency of magnet ingestion was compared over 3 eras: (1) pre-ban (2008-2012), (2) intra-ban (2013-2016), and (3) post-ban (2017-2020). RESULTS: There were 167 magnet ingestions, including 99 with multiple magnets. Most patients (59%) were male and median age was 6 (interquartile range, 3-9) years. Most single magnet ingestions (86%) were discharged with outpatient monitoring, and none experienced severe outcomes. Multiple magnet ingestions led to significant morbidity including hospitalizations (68%), endoscopic procedures (48%), surgical procedures (14%), and severe outcomes (12%). Most patients (75%) were asymptomatic, however, there was a higher risk of surgery and severe complications based on the presence of symptoms ( P = 0.003). The rate of surgical intervention was higher with ≥3 magnets (31.7%) compared to 2 magnets (2.4%) ( P < 0.003). Additionally, we found an 160% increase in children with magnet ingestions in the post-ban period ( P = 0.021). CONCLUSIONS: Multiple magnet ingestion is associated with high morbidity and rate of severe outcomes. There is a relationship between public policy of magnet sale and frequency of magnet ingestion.

Ruxolitinib: Targeted Approach for Treatment of Autoinflammatory Very Early Onset Inflammatory Bowel Disease.

Very early onset inflammatory bowel disease (VEO-IBD), diagnosed <6 years old, can be genetically and phenotypically distinct and more refractory than older-onset IBD. Identified causal monogenic defects have been targeted therapeutically in a small subset of VEO-IBD1; however, for most of these children, treatment strategies, such as phenotypic profiles, are critically needed to improve outcomes.

Novel mutations in NOTCH2 gene in infants with neonatal cholestasis.

One cause of neonatal cholestasis (NC) is paucity of intrahepatic bile ducts which can be associated with Alagille syndrome or non- syndromic. Alagille syndrome is caused by autosomal dominant mutations in the Notch signaling pathway ligand Jagged1 in 94% of patients and mutations in the NOTCH2 receptor in <1% of patients. This is a retrospective case series studying infants with neonatal cholestasis found to have variants of unknown significance (VOUS) in NOTCH2. Sorting intolerant from tolerant (SIFT) and polymorphism phenotyping (PolyPhen) were utilized to predict a damaging effect. Five infants with NC without other features of Alagille syndrome were found to have one copy of a VOUS in NOTCH2, predicted to be damaging by SIFT and PolyPhen. Our cases support the notion that NOTCH2 mutations may result in hypoplastic biliary system. Further characterization of these variants is important to assist with our clinical approach to NC.

Pediatric oncologist willingness to offer germline TP53 testing in osteosarcoma.

BACKGROUND: Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by mutations in the tumor-suppressor gene TP53. Osteosarcoma is a sentinel cancer in LFS. Prior studies using Sanger sequencing platforms have demonstrated that 3% of individuals with osteosarcoma harbor a mutation in TP53. New data from next-generation sequencing have demonstrated that 3.8% of patients with osteosarcoma have a known pathogenic variant, and an additional 5.7% carry exonic variants of unknown significance in TP53. METHODS: Pediatric oncologists were e-mailed an anonymous 18-question survey assessing their willingness to offer TP53 germline testing to a child with osteosarcoma with or without a family history, and they were evaluated for changes in their choices with the prior data and the new data. RESULTS: One hundred seventy-seven pediatric oncologists (22%) responded to the survey. Respondents were more likely to offer TP53 testing to a patient with a positive family history (77.4% vs 12.4%; P < .0001). Significantly more providers responded that they would offer TP53 testing once they were provided with the new data (25.4% vs 12.4%; P = .0038). The proportion of providers who responded that they were unsure increased significantly when they were presented with the new data (25.4% vs 10.2%; P = .0002). Potential implications for other family members and the possibility that surveillance imaging would detect new malignancies at an earlier stage were important factors influencing a provider's decision to offer TP53 testing. CONCLUSIONS: Recent data increase the proportion of providers willing to offer testing, and this suggests concern on the part of pediatric oncologists that variants of unknown significance may be disease-defining in rare cancers. Cancer 2018;124:1242-50. © 2018 American Cancer Society.