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BACKGROUND AND AIMS: Colonic eosinophilia, an enigmatic finding often referred to as eosinophilic colitis (EoC), is a poorly understood condition. Whether EoC is a distinct disease or a colonic manifestation of eosinophilic gastrointestinal diseases (EGIDs) or inflammatory bowel disease (IBD) is undetermined. METHODS: Subjects with EoC (n=27) and controls (normal [NL, n=20], Crohn disease [CD, n=14]) were enrolled across sites associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). EoC was diagnosed as colonic eosinophilia (ascending ≥100, descending ≥85, sigmoid ≥65 eosinophils/high-power field) with related symptoms. Colon biopsies were subjected to RNA sequencing. Associations between gene expression and histologic features were analyzed with Spearman correlation; operational pathways and cellular constituents were computationally derived. RESULTS: We identified 987 differentially expressed genes (EoC transcriptome) between EoC and NL (>1.5-fold change, P < .05). Colonic eosinophil count correlated with 31% of EoC transcriptome, most notably with CCL11 and CLC (r=0.78 and 0.77, P < .001). Among EoC and other EGIDs, there was minimal transcriptomic overlap; and minimal evidence of a strong allergic type 2 immune response compared with other EGIDs. Decreased cell-cycle and increased apoptosis in EoC compared with NL were identified by functional enrichment analysis and immunostaining using Ki-67 and cleaved caspase-3. Pericryptal circumferential eosinophil collars were associated with the EoC transcriptome (P < .001). EoC transcriptome-based scores were reversible with disease remission and differentiated EoC from IBD, even after controlling for colonic eosinophil levels (P < .0001). CONCLUSION: We established EoC transcriptomic profiles, identified mechanistic pathways, and integrated findings with parallel IBD and EGID data. These findings establish EoC as a distinct disease compared with other EGIDs and IBD, thereby providing a basis for improving diagnosis and treatment.

Primary gastric Burkitt's lymphoma (BL) is rare in the pediatric population. Furthermore, the association of Burkitt's lymphoma with Helicobacter pylori is not well defined. We report a case of primary gastric Burkitt's lymphoma associated with Helicobacter pylori diagnosed in a pediatric patient. This diagnosis was made with the aid of endoscopic ultrasound (EUS)-guided fine-needle biopsy (FNB). This is one of the first pediatric cases of EUS-guided FNB for the diagnosis of H. pylori-associated gastric BL.

Objectives: Eosinophilic esophagitis (EoE) is a clinicopathologic disorder characterized by infiltration of eosinophils into the esophagus. Primary treatment approaches include topical corticosteroids and/or food elimination. The aim of the present study was to compare the effectiveness of combination therapy (topical corticosteroid plus test-based food elimination [FS]) with single therapy (topical corticosteroid [S] or test-based food elimination [F]). Methods: Chart review of patients with EoE at Texas Children's Hospital (age

Eosinophilic esophagitis (EoE) is an allergen-mediated, clinicopathological condition affecting all ages. The characteristics of children with EoE in the southwestern USA have not been fully described. Furthermore, very little is known about the relationship between parental allergies and risk of EoE in their offspring in this patient population. To characterize children with EoE and to examine the relationship between prevalence of parental allergies and occurrence of EoE in their offspring at a single referral pediatric center in the southwestern USA. Demographic and clinical information of 126 children (≤18 years of age) with EoE was abstracted in a pre-determined data extraction form and analyzed. The allergy history was collected from biological parents of 61 children (parent–child cluster) with EoE in a standardized questionnaire and analyzed. The median age at presentation was 8 years (interquartile range 4–13). The majority of our patients were male (71 %) and Caucasian (59 %). Overall, 84 % of children reported allergies. Prevalence of food allergy was significantly higher compared to environmental allergies (P = 0.001). At least 46 % of parents reported allergies. A significantly higher proportion of fathers had developed allergies during their childhood compared to adulthood (P = 0.03). The characteristics of EoE in our patients were similar to those reported from other parts of the country. Childhood onset of paternal allergies appears to be a risk factor for occurrence of EoE in their offspring. Additional research to elucidate the relationship between parental allergies and occurrence of EoE in their offspring is warranted.

Esophageal food impaction (EFI) can be the initial presentation of eosinophilic esophagitis (EoE). EoE is characterized by persistent esophageal eosinophilia (EE). Both EFI and EE are related to a variety of conditions. To date, the relationship between EFI, EE, and EoE remains unclear. To review our institutional experience with EFIs and combine our knowledge with the existing literature to conduct a systematic review and meta-analysis for delineating the relationship between EFI, EE, and EoE. We reviewed medical records of 72 children with EFI presenting to our emergency center between 2007 and 2013. PubMed, EMBASE, and Scopus databases were screened from inception until July 2014 to identify studies linking EFI and EoE. Included studies were methodically assessed for the quality and strength of association between EFI and EoE. Our institutional experience highlighted the possibility of proton-pump inhibitor therapy-responsive EE (PPI-REE) as an underrecognized risk factor for EFI. A systematic review of 14 studies, including ours, revealed that most studies did not eliminate other causes of EFI or EE. The meta-analysis revealed that esophageal biopsies were obtained from 54 % (40–68) of individuals presenting with EFI, and the overall EoE-attributable EFI among those who were biopsied was 54 % (43–65). Substantial heterogeneity was noted among the studies. PPI-REE is an underestimated risk factor for EFI. The quality of existing evidence linking EFI and EoE is limited by several important factors. Future studies with robust design are warranted to delineate the relationship between EFI, EE, and EoE.

Objective: Eosinophilic esophagitis (EoE) is a chronic esophageal inflammatory condition with a paucity of information on health-related quality of life (HRQOL). The objective of the study was to report on the measurement properties of the PedsQL EoE Module. Methods: The PedsQL EoE Module was completed in a multisite study by 196 pediatric patients with EoE and 262 parents of patients with EoE. Results: The PedsQL EoE Module scales evidenced excellent feasibility (0.6%–3.1% missing), excellent group comparison reliability across total scale scores (patient a 0.93; parent proxy a 0.94), good reliability for the 7 individual scales (patient a 0.75–0.87; parent proxy a 0.81–0.92), excellent test–retest reliability (patient intraclass correlation coefficient 0.88; parent intraclass correlation coefficient 0.82), demonstrated no floor effects and low ceiling effects, and demonstrated a high percentage of scaling success for most scales. Intercorrelations with the PedsQL Generic Core Scales were in the medium (0.30) to large (0.50) range. PedsQL EoE Module scores were worse among patients with active histologic disease (� 5 eos/hpf) compared with those in remission (patient self-report: 63.3 vs 69.9 [P < 0.05]; parent proxy report: 65.1 vs 72.3 [P < 0.01]), and those treated with dietary restrictions compared with those with no restrictions (patient self-report: 61.6 vs 74.3 [P < 0.01]; parent proxy report: 65.5 vs 74.7 [P < 0.01]). Conclusions: The results demonstrate excellent measurement properties of the PedsQL EoE Module. Patients with active histologic disease and those treated with dietary restrictions demonstrated worse PedsQL scores. The PedsQL EoE Module may be used in the evaluation of pediatric EoE diseasespecific HRQOL in clinical research and practice.

New geologic mapping reveals that Artemis, a unique 2400-km-diameter feature on Venus, is much larger than previously recognized, including a wide outer trough (>5000 km diameter), a radial dike swarm (12,000 km diameter), and a concentric wrinkle ridge suite (13,000 km diameter). Artemis's evolution included formation of its interior and chasma, accompanied by lateral propagation of radial dikes. The escape of dike magma to the surface formed local cover deposits that buried parts of the remaining radial fracture suite. Cover deposits are cut, in turn, by wrinkle ridges that likely formed by coupling of convective mantle flow with the lithosphere. The outer trough formed late relative to radial fractures, cover deposits, and wrinkle ridges. We suggest that Artemis represents the magmatic signature of a deep mantle plume acting on relatively thin lithosphere. As such, it appears to represent the largest tectonomagmatic feature in the solar system. The newly recognized vast extent of Artemis holds implications for the formation of giant radial dike swarms, wrinkle ridge formation, terrestrial planet mantle-lithosphere coupling, and Venus's surface and geodynamic evolution.

Background & Aims A 6-food elimination diet induces remission in most children and adults with eosinophilic esophagitis (EoE). The effectiveness of empiric elimination of only 4 foods has not been studied in children. We performed a prospective observational outcome study in children with EoE treated with dietary exclusion of cow's milk, wheat, egg, and soy. The objective was to assess the clinical, endoscopic, and histologic efficacy of this treatment in EoE. Methods We recruited children (1–18 years old, diagnosed per consensus guidelines) from 4 medical centers. Study participants (n = 78) were given a proton pump inhibitor twice daily and underwent a baseline esophagogastroduodenoscopy. Subjects were instructed on dietary exclusion of cow's milk, wheat, egg, and soy. Clinical, endoscopic, and histologic assessments were made after 8 weeks. Responders had single foods reintroduced for 8 weeks, with repeat endoscopy to assess for recurrence of active disease. The primary endpoint was histologic remission (fewer than 15 eosinophils per high-powered field). Secondary endpoints included symptom and endoscopic improvements and identification of foods associated with active histologic disease. Results After 8 weeks on 4-food elimination diet, 50 subjects were in histologic remission (64%). The subjects' mean baseline clinical symptoms score was 4.5, which decreased to 2.3 after 8 weeks of 4-food elimination diet ( P P Conclusions In a prospective study of children with EoE, 8 weeks of 4-food elimination diet induced clinical, endoscopic, and histologic remission in more than 60% of children with EoE. Although less restrictive than 6-food elimination diet, 4-food elimination diet was nearly as effective, and can be recommended as a treatment for children with EoE.

Human saliva is a complex fluid, rich in immunological components, which reflects real time systemic concentrations. Advances in biotechnology have enabled us to measure minute concentrations of immunological components such as cytokines in saliva samples with precision and accuracy 1. There are few data evaluating how the collection method may influence the results in addition to other methodological challenges, resulting in lack of consensus on a universally accepted saliva collection technique2, especially in children. Specifically, the impact of saliva collection methods on detection and analysis of salivary concentrations of allergic inflammatory cytokines such as the interleukin (IL)-4, IL-5, IL-13, eotaxin 3 (Eo3) and thymic stromal lymphopoietin (TSLP), that mediate allergic inflammation3 has not been reported. These cytokines play an important role in the development of allergic inflammatory states in increasingly prevalent conditions such as allergic rhinitis (AR), food allergy (FA), asthma (AS), atopic dermatitis (AD), and eosinophilic esophagitis (EoE)4. The overall goal of this study was to compare two methods of saliva collection in the detection and analysis of salivary concentrations of IL-4, IL-5, IL-13, Eo3 and TSLP in children. Our study was approved by the Baylor Institutional Review Board and informed consent was obtained from the parent and assent, where appropriate, from the child. We studied 20 children; median age: 14 years (9–17, IQR), female: 14 (64%), Caucasian: 13 (59%). Three (15%) children did not report any allergies and the remaining 17 (85%) children reported one or more of following commonly prevalent allergic conditions: AD (n=1), oral allergy syndrome (n=1), AS (n=2), FA (n=2), AR (n=6) and EoE (n=9). No attempt was made to distinguish salivary cytokine profiles between children with and without allergies in this study. Participants were nil per os for at least 4 hours. They rinsed their mouth with water, and following a 10 min. period, passive drool (PD) was collected followed by saliva collection via an oral swab (OS), in order to minimize the effect of saliva on the flow rate and concentration of cytokines in PD. PD samples were obtained with the head tilted forward while drooling down a 5.5 cm polypropylene Salimetrics Collection Aid® (Salimetrics LLC, State College, PA). Next, the participant placed a Salimetrics Oral Swab® (Salimetrics LLC, State College, PA) in their mouth and gently rolled it side-to-side for approximately 60–90 sec. to saturate the swab, which was then placed in a storage tube that allows saliva to be centrifuged. All samples were collected between 7:30 am and 12:30 pm. Two (9%) participants aged 11 and 14 years were unable to provide PD because they were not able to direct their drool into the collection device. All participants were able to use the OS. After providing paired saliva samples, all children responded to a short questionnaire assessing their knowledge of salivary diagnostics, asking them to rate their experience in providing each saliva sample in terms of perceived ease of use, acceptability and safety. Only 23% were aware of saliva testing in the surveillance of health or disease. A significantly higher proportion of children preferred the OS over PD sampling (82 % vs. 18 %; P < 0.05). Ease (68%) and speed (14%) of providing samples were the most common reasons cited by those who preferred the OS. Saliva samples were maintained at 4°C and transport ed to the laboratory within 2 hr of collection and were centrifuged at 3,000 rpm for 15 minutes. Supernatants were stored in aliquots and frozen at −80°C. On the day of anal ysis, samples were brought to room temperature, vortexed, and centrifuged for 15 minutes at 3,000 rpm. A magnetic, high sensitivity human multi-analytes profiling bead-based assay kit was used (EMD Millipore, Billerica, MA; lower limit of detection (LLD) for IL-4, IL-5, and IL-13: 0.13 pg/mL, and coefficient of variation (CV) < 10%

Abnormal cytokine production by T-helper 1 (Th1)/T-helper 2 (Th2) lymphocytes has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Few studies have examined Th1/Th2 cytokine status in pediatric IBD patients, and results have been inconsistent. We used flow cytometric detection of intracellular IFN-gamma/IL-4 cytokine production to investigate CD4+, Th1, and Th2 cells in the peripheral blood of children with untreated, newly diagnosed Crohn's disease (CD) (n = 23) and matched healthy controls (n = 49). Th1 cytokine levels were lower in CD patients compared with controls (p = 0.006) and strongly correlated with levels of albumin and hematocrit (r = 0.51, p = 0.007 and r = 0.35, p = 0.052, respectively). An age-dependent increase in Th1 cells was observed (p < 0.0005); however, no correlation was found between age, clinical end points, %CD4+, or Th2 cell numbers. In conclusion, the Th1 cytokine levels in blood are lower in early onset CD patients than in healthy children and are directly associated with disease-related clinical parameters. In future studies of pediatric IBD patients, it will be critical to consider the effect of age and disease progression on cytokine status in intestinal mucosa and peripheral blood.

G A A b st ra ct s calculated at baseline and at week 12. Proximal and distal esophageal scores, total scores (summation of proximal and distal), and subscores for individual component of EREFS (edema, rings, exudates, furrows, stricture) were prospectively recorded. Baseline and followup EREFS scores were compared, and post-treatment eosinophil counts and EREFS scores were correlated. Data analysis was performed on the intent-to-treat population. Results: A total of 93 subjects were randomized from 25 centers, and 87 were included in the final analysis. 97% of subjects had endoscopic features identified at baseline. The OBS (n= 49) and placebo (n=38) groups did not differ in baseline demographic and endoscopic characteristics. EREFS scores significantly improved after treatment in both proximal (3.4 to 1.5; p