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Silvana Bonilla, Samuel Nurko Division of Pediatric Gastroenterology, Hepatology and Nutrition, Boston Children’s Hospital. Boston, MA, USA Abstract: Chronic abdominal pain is frequently encountered in pediatric practice. A large proportion of cases meet Rome criteria for abdominal pain-functional gastrointestinal disorders (AP-FGIDs). These disorders are costly and, in some cases, lead to impairment of daily functioning and overall quality of life. Pathophysiologic mechanisms include early stressful events, visceral hypersensitivity, dysmotility, changes in intestinal microbiota, and altered central nervous system processing. They are considered disorders of the brain–gut interaction. The diagnosis is made on clinical grounds using symptom-based criteria (Rome criteria). Anxiety and depressive symptoms are more prevalent in patients with AP-FGIDs. Therefore, attention has been directed to the use of neuromodulators as potential interventions for AP-FGIDs. Antidepressants are one type of neuromodulators, and one of the most studied drugs for the management of AP-FGIDs in adult and pediatric population. Data available in pediatric population have significant limitations including nonuniform methodology with different study designs and primary endpoints. Evidence of the efficacy of antidepressants in the management of pediatric AP-FGIDs is not consistent. There is an urgent need for well-designed randomized clinical trials using age-appropriate validated outcome measures. Careful consideration must be given to adverse effects, particularly increased suicidal ideation. Keywords: tricyclic antidepressants, SSRI, functional gastrointestinal disorders, children

Background Food allergies are a growing health problem, and the development of therapies that prevent disease onset is limited by the lack of adjuvant-free experimental animal models. We compared allergic sensitization in patients with food allergy or Wiskott-Aldrich syndrome ( WAS) and defined whether spontaneous disease in Was −/− mice recapitulates the pathology of a conventional disease model and/or human food allergy. Methods Comparative Immuno CAP ISAC microarray was performed in patients with food allergy or WAS. Spontaneous food allergy in Was −/− mice was compared to an adjuvant-based model in wild-type mice ( WT- OVA/alum). Intestinal and systemic anaphylaxis was assessed, and the role of the high-affinity IgE Fc receptor (Fcε RI) in allergic sensitization was evaluated using Was −/− Fcer1a −/− mice. Results Polysensitization to food was detected in both WAS and food-allergic patients which was recapitulated in the Was −/− model. Oral administration of ovalbumin (OVA) in Was −/− mice induced low titers of OVA-specific IgE compared to the WT- OVA/alum model. Irrespectively, 79% of Was −/− mice developed allergic diarrhea following oral OVA challenge. Systemic anaphylaxis occurred in Was −/− mice (95%) with a mortality rate >50%. Spontaneous sensitization and intestinal allergy occurred independent of Fcε RI expression on mast cells (MCs) and basophils. Conclusions Was −/− mice provide a model of food allergy with the advantage of mimicking polysensitization and low food-antigen IgE titers as observed in humans with clinical food allergy. This model will facilitate studies on aberrant immune responses during spontaneous disease development. Our results imply that therapeutic targeting of the IgE/Fcε RI activation cascade will not affect sensitization to food. [ABSTRACT FROM AUTHOR]

Background The differential diagnosis of intractable reflux in children includes rumination syndrome, but confirming the diagnosis using antroduodenal manometry is invasive, is costly, and requires anesthesia. High-resolution esophageal manometry with impedance ( HRM- MII) overcomes these limitations, and the goal of this study is to validate the use of HRM- MII as a diagnostic tool for rumination and to describe the subtypes of pediatric rumination. Methods We reviewed the HRM- MII tracings of 21 children presenting with symptoms of intractable reflux in whom rumination was being considered. Patients underwent a standard and post-prandial HRM- MII. Peak intraluminal esophageal pressures, baseline gastric and thoracic pressures, and the timing of the R wave relative to LES relaxations and bolus flow were recorded. Chi-square analyses were used for comparison of proportions and means were compared using t-tests or non-parametric equivalent. Key Results Forty-one (55.5%) primary and 33 (44.5%) secondary rumination episodes were seen. Three types of primary rumination were identified: i) LES relaxation without retrograde flow preceding the R wave (51% of episodes); ii) LES relaxation after the R wave (20% of episodes); and iii) R waves with no LES relaxation (29% of episodes). Eleven patients had rumination episodes with a peak gastric pressure <30 mm Hg. A total of 44 (60%) rumination episodes occurred during the standard HRM- MII, and 30 (40%) occurred during or after the meal. Conclusions & Inferences HRM- MII can accurately diagnose rumination in children. We identify three types of primary rumination which may provide insight into therapeutic response. [ABSTRACT FROM AUTHOR]