Esophageal Distensibility Defines Fibrostenotic Severity in Pediatric Eosinophilic Esophagitis.

BACKGROUND & AIMS: Identification of fibrosis in pediatric eosinophilic esophagitis (EoE) relies on symptom assessment and endoscopy. Symptoms are highly variable, and early fibrotic remodeling may go undetected on endoscopy yet contribute to esophageal dysfunction. We aimed to assess whether esophageal distensibility has utility in defining fibrostenotic severity in a cohort of pediatric patients with EoE with symptoms of esophageal dysfunction. METHODS: We analyzed a prospectively recruited a cohort of children ages 9 to 21 years undergoing upper endoscopy and Endoscopic Functional Lumen Imaging Probe (EndoFLIP) for suspected or previously diagnosed EoE. Esophageal distensibility was evaluated by the distensibility index (DI) and esophageal diameter at the distensibility plateau. The association of esophageal distensibility to clinical, endoscopic, and histologic parameters of disease severity was assessed. Receiver operating characteristic analysis was performed to determine the utility of distensibility in defining esophageal rigidity in pediatric EoE. RESULTS: We identified 59 pediatric patients with EoE undergoing endoscopy and EndoFLIP at a single pediatric tertiary referral center. DI (mm2/mmHg) was significantly lower in patients with fibrotic as compared with inflammatory features on endoscopy (median, 3.3; interquartile range, 2.3-4.4) vs median, 5.5; interquartile range, 4.1-6.0; P = .02) and showed no correlation with eosinophil count. DI <4.5 mm2/mmHg predicted grade 2 rings on endoscopy with area under the curve of 0.81 (P = .0004). DI predicted food impaction in both unadjusted and adjusted models (fully adjusted odds ratio, 1.44; 95% confidence interval, 1.02-2.14; P = .0486). CONCLUSION: Esophageal distensibility determined by EndoFLIP is a measure of fibrostenotic severity that can be used to clinically phenotype pediatric EoE. We propose parameters of DI <4.5 mm2/mmHg for defining esophageal rigidity in pediatric patients with EoE ages 9 years and older.

A Case of Syphilitic Hepatitis in an Adolescent.

The incidence of syphilis is rising among adolescents necessitating improved provider awareness and screening practices. We present a case of an adolescent with acute hepatitis ultimately diagnosed with secondary syphilitic hepatitis. Clinical presentation, laboratory abnormalities, and histologic features of syphilitic hepatitis are nonspecific, with diagnosis relying on clinical suspicion and targeted testing. This case highlights the importance of screening for syphilis in sexually active adolescents with acute hepatitis. The rising incidence of syphilis among adolescents, and the variety of clinical manifestations including those commonly seen by pediatric gastroenterologists, makes elevated clinical suspicion essential to prompt diagnosis and treatment. With improved provider awareness across general pediatric and subspecialty providers, the transmission of syphilis among adolescent patients can be reduced.

Food protein-induced enterocolitis syndrome: Dynamic relationship among gastrointestinal symptoms, immune response, and the autonomic nervous system.

OBJECTIVE: To explore the relationship among gastrointestinal (GI) symptoms, immune response, and autonomic nervous system (ANS) in food protein-induced enterocolitis syndrome (FPIES) in relation to the current understanding of disease phenotype and pathogenesis. DATA SOURCES: Relevant studies related to FPIES, GI symptomatology, and ANS were reviewed. Literature search was performed using PubMed, with keyword combinations including but not limited to FPIES, allergic GI disorders, ANS, autonomic dysfunction, dysautonomia, GI, diarrhea, vomiting, neuroimmune, and clinical phenotyping tools. STUDY SELECTIONS: Peer-reviewed case-control studies, observational studies, reviews and guidelines, and systematic reviews related to FPIES and ANS were selected for review. RESULTS: There is limited research directly relating GI symptoms and FPIES to the ANS and immunologic response. To support the proposed mechanisms of action related to patient symptoms, studies relevant to coexisting GI-autonomic processes and FPIES immunologic triggers were examined. These related disease processes were extrapolated to FPIES based on the current knowledge of FPIES phenotype and pathogenesis. CONCLUSION: The etiology of FPIES and the underlying mechanisms triggering symptoms are not well understood. On the basis of the exaggerated GI symptoms and hemodynamic response observed, the ANS likely plays an important role in FPIES, possibly as a compensatory response. The trigger for this cascade of symptoms may be related to the disruption of immunologic homeostasis that typically contributes to immune tolerance. To more accurately evaluate FPIES pathophysiology necessitates understanding the diverse spectrum of presenting symptoms. A consistent and comprehensive symptom assessment tool may improve our understanding of this dynamic relationship.

AAV mediated GDNF secretion from retinal glia slows down retinal degeneration in a rat model of retinitis pigmentosa.

Mutations in over 80 identified genes can induce apoptosis in photoreceptors, resulting in blindness with a prevalence of 1 in 3,000 individuals. This broad genetic heterogeneity of disease impacting a wide range of photoreceptor functions renders the design of gene-specific therapies for photoreceptor degeneration impractical and necessitates the development of mutation-independent treatments to slow photoreceptor cell death. One promising strategy for photoreceptor neuroprotection is neurotrophin secretion from Müller cells, the primary retinal glia. Müller glia are excellent targets for secreting neurotrophins as they span the entire tissue, ensheath all neuronal populations, are numerous, and persist through retinal degeneration. We previously engineered an adeno-associated virus (AAV) variant (ShH10) capable of efficient and selective glial cell transduction through intravitreal injection. ShH10-mediated glial-derived neurotrophic factor (GDNF) secretion from glia, generates high GDNF levels in treated retinas, leading to sustained functional rescue for over 5 months. This GDNF secretion from glia following intravitreal vector administration is a safe and effective means to slow the progression of retinal degeneration in a rat model of retinitis pigmentosa (RP) and shows significant promise as a gene therapy to treat human retinal degenerations. These findings also demonstrate for the first time that glia-mediated secretion of neurotrophins is a promising treatment that may be applicable to other neurodegenerative conditions.