18% added an immunomodulator, 10% had dose escalation of their current therapy and18% had a change within medication class. VCE was abnormal in 94% of those who hadchange in treatment. VCE revealed more extensive small bowel involvement than concurrentsmall bowel imaging modalities in 27% (3/11) of patients. Abnormal VCE results was mostcommonly (63%) seen in those CD patients on treatment with decreased height velocity.These patients had mean z-scores pre and 12 months post-VCE of -0.5 and -0.1, respectively(p=0.02). Overall, mean BMI's also improved from 18.9 to 19.9 (p=.001). ESR decreasedsignificantly after change in treatment post VCE (23 vs.15 p=0.004). VCE was able to “ruleout” IBD in 94% of those who had suspected IBD, while 50% of patients with presumedUC or IBDU had diagnosis changed to CD. Conclusion: VCE provides an additive clinicalbenefit in pediatric patients with IBD requiring further small bowel evaluation despite activetreatment especially in the face of poor growth. VCE can help “rule out” IBD, as well ashelp lead to diagnostic reclassification of patients with UC or IC. Though more prospectivestudies are needed, VCE can be very useful in decision making and monitoring inpediatric IBD.

Sa1996

Crohn's Disease Associated NOD2 Variants Show Differential Activation ofNFkB in Response to Autosignaling and Muramyl DipeptideJohan Van Limbergen, Fraser Soares, Richard K. Russell, Stephen Girardin, Anne M.Griffiths, Dana Philpott

Background: Single nucleotide polymorphisms (SNPs) located of the NOD2/CARD15 gene(nucleotide-binding oligomerization domain containing 2/caspase recruitment domain fam-ily, member 15) are associated with increased susceptibility to Crohn's disease (CD). TheseSNPs are thought to disrupt the sensing of bacterial muramyl dipeptide (MDP) at the C-terminus of the NOD2 protein. The precise contribution of each of these SNPs (SNP5, 8,12 and 13) to NF-kB activation by means of NOD2-auto-signaling and stimulation withMDP has not been investigated at low levels of NOD2 expression. Data regarding the linkagedisequilibrium (LD) between these CD-associated SNPs are scarce. Methods: NOD2 variantconstructs (rs2066842 (SNP5), rs2066844 (SNP8), rs2066845 (SNP12) and rs2066847(SNP13), SNP5+8, SNP5+12 and SNP5+13) were created by site-directed mutagenesis of apCMV plasmid containing wild-type N-terminal FLAG-NOD2. NF-kB luciferase assays wereperformed on HEK293 cells following transient transfection (20hr) with wildtype (WT) andNOD2 variant constructs, titrating NOD2 from 1-100ng/well. The NF-kB luciferase responseof NOD2 (1ng)-transfected HEK293 cells to MDP (10microgram/well) was measured. 2-way ANOVA and unpaired t-tests were used. By means of Haploview-analysis of sequencingdata of the exons and exon-intron boundaries in 24 paediatric Caucasian Crohn's diseasepatients, we assessed the LD between SNP5 and SNP8, 12 and 13. Results: 2-way ANOVAdemonstrated an effect of NOD2 genotype and concentration on auto-signaling at low levelsof expression (p<0.0001). This was due to the significant difference of auto-activationbetween WT and SNP5, SNP8 and SNP12 (p<0.001). At low levels of NOD2 expression(1-2ng), the presence of SNP5 modified the auto-activating potential of SNP12 (p<0.01).Based on these titration experiments, a low NOD2 transfection of 1ng/well was chosen forthe MDP-stimulation experiment. MDP stimulation led to a significant increase of NF-kBluciferase activity in WT and all NOD2 variant constructs, except SNP13 and SNP5+13(p<0.0001). Haplotype analysis of 11 NOD2 SNPs, identified through direct sequencing in24 children with CD, showed that LD between SNP5 and the other CD-associated variantsis low (r-squared <0.1), in spite of close physical proximity (D' 1.0). Conclusion: Ourcombined genetic and functional analyses demonstrate that the association of SNP5 withCrohn's disease is unlikely due to LD with other SNPs. At low levels of NOD2 expression,NOD2 variant constructs differ from WT in their auto-signaling and MDP-stimulated activa-tion of NF-kB.

Sa1997

Monitoring Crohns Disease Activity in Children: A Retrospective Comparisonof Transabdominal Ultrasound and IleocolonoscopyKerri L. Novak, Gilaad G. Kaplan, Remo Panaccione, Subrata Ghosh, Jennifer deBruyn,Clara L. Ortiz-Neira, Stephanie Wilson

Background: Monitoring pediatric inflammatory bowel disease (IBD) is challenging as chil-dren require general anesthetic for endoscopy and they are particularly vulnerable to potentialadverse effects of ionizing radiation, present with computed tomography. Routine access toother modalities, such as magnetic resonance, is limited. Therefore, safe, tolerable, andaccessible means of evaluating inflammatory activity in IBD is key to direct medical manage-ment. Data to support the use of US in monitoring pediatric IBD is limited. Objective: Tocompare sonographic and colonoscope features of inflammation in a group of pediatric IBDpatients. Methods: This is a University of Calgary Ethics Board approved study. IBD patientswere from an established database of children with IBD and cross-referenced with a radiologydatabase. Luminal sonographic images and endoscopic findings from pediatric patients withIBD and controls were reviewed. Only patients having ileocolonoscopy within 3 months ofultrasound were included. Inflammatory US parameters included bowel wall thickness,presence of mesenteric inflammatory fat, lymphadenopathy, and hyperemia (detectable colorDoppler signal within the bowel wall). The Mann-Whitney U-Test was utilized to compareultrasound with endoscopic finding, the Signed Rank test was used to assess the relationshipbetween endoscopic and US disease severity and T-tests were used to compare US parametersin IBD patients versus control patients. Results: This is the largest retrospective pediatricUS study known to date. A total of 103 patients were evaluated: 72.8% (n=75) had confirmedIBD, 80% (n=60) had Crohns disease, 17.3% (n=13) had ulcerative colitis, 2.7% (n=2) hadindeterminant colitis and 27.1% (n=28) were healthy. 17.4% of patients were treated withBiologics, 53.3% with immune modulators and 30.7% with corticosteroids. 20% (n=15) ofpatients had a least one prior surgery. When US was compared with endoscopy (n=32)there were no significant differences found (p>0.05) with regard to disease severity, bowelwall thickness, hyperemia, number of lymph nodes or presence of inflammatory fat. Alternat-ively, ileal thickness showed the strongest difference between patients with IBD and controls(p<0.0001). The positive predictive value (PPV) of US for all disease states (remission, mild,moderate and severe) was found to be 89.6% and negative predictive value was 100%.

S-377 AGA Abstracts

Conclusion: Transabdominal US is effective in identifying remissive, mild, moderate andsevere IBD. These results argue that US is a compelling adjunctive modality for monitoringpediatric inflammatory bowel disease.

Sa1998

The Probiotic VSL#3 in Children With Crohn Disease in RemissionAndrew S. Day, Steven T. Leach, Thomas A. Judd, Kashan Baba, Rebecca J. Hill, DanielA. Lemberg

Background and Aims: VSL#3, a probiotic preparation containing 8 bacterial strains at ahigh concentration, has proven clinical efficacy in the induction andmaintenance of remissionof ulcerative colitis in children and adults. However, the role of this agent in the maintenanceof remission in conjunction with standard therapy has not yet been evaluated in pediatricCrohn disease (CD). The primary aim of this study was to assess the role of VSL#3 in themaintenance of remission of children with CD, whilst secondary end-points included serumand faecal inflammatory markers, growth parameters and quality of life (QOL) scores.Methods: A randomised, double-blind, placebo-controlled study was conducted in childrenaged between 4 and 18 years with existing diagnosis of CD. Additional inclusion criteriawas current remission based upon Pediatric CD Disease Activity Index (PCDAI) scores lessthan 15. Children were randomised to receive active probiotic (standard dose of 1,800million organisms daily with adjustment for weight) or placebo for 12months, with evaluationof length of remission, requirement for rescue therapy, serum and faecal inflammatorymarkers, growth and quality of life (QOL) scores. Results: Data from 28 children was availablefor evaluation. Twelve children (10 boys) of average age of 13.3 (SD 3.0) years wererandomised to receive VSL#3 and 16 children (11 boys) with mean age of 13.9 (SD 2.4)years were randomised to receive placebo. At baseline PCDAI scores, serum inflammatorymarkers and growth parameters were not different between the groups. QOL scores werenot different at baseline or at any subsequent time-points between the two groups (p>0.05).Relapse rates did not differ between the two groups (p>0.05). Platelet counts were greaterat 6 months in the placebo group compared to the probiotic group (310 ± 58 vs 254 ± 58:p=0.03). Other serum inflammatory markers did not differ between the two groups at anytime points. Levels of the fecal inflammatory marker, S100A12, appeared higher in theplacebo group than the probiotic group at months 6, 9 and 12, and indeed approachedsignificance at month 6 (p < 0.055). Conclusions: In this 12 month study in children withCD in remission, high-dose probiotic therapy did not influence the relapse rate when assessedin comparison to standard therapy. However, there was a trend towards decreasing faecalmarkers of gut inflammation with VSL#3, and such results need to be confirmed in a largerstudy. In consideration of its beneficial effects on inflammatory and nutritional parametersin pediatric patients with active CD (Day et al, DDW 2012), we hypothesize that betterresults could be observed in the quiescent phase of the disease if VSL#3 supplementationis started during active disease.

Sa1999

Characteristics of Racially Diverse Pediatric Inflammatory Bowel Disease(IBD) PopulationGitit Tomer, Yolanda Rivas, John F. Thompson

Background: IBD is increasingly recognized in diverse ethnic populations. In the UnitedStates, IBD among minorities has not been thoroughly studied and there are scarce dataregarding disease presentation and laboratory values. Objective: To characterize the clinicalphenotype of racially diverse pediatric IBD population. Methods: A retrospective chart reviewof patients with IBD who are followed in Pediatric Gastroenterology was performed. Detailedphenotypic information was obtained and biomarkers at diagnosis were recorded, includinghemoglobin, platelet count, serum albumin, sedimentation rate (ESR) and C-reactive protein(CRP). Results: Seventy four patients were studied: 58 with Crohn's disease (CD), 14 withulcerative colitis (UC) and 2 IBD unclassified. At diagnosis the mean age was 12.7; 31%were female. Only 19% of our patients were Caucasian and the remainder were minoritypatients. Among CD patients, 66% had ileocolonic disease and 57% had upper tract disease;22% had penetrating disease and 16% had stricturing disease. At diagnosis 34% werehospitalized and only 5% had positive family history of IBD. The mean duration of symptomsbefore diagnosis was 25 weeks. The most frequent presenting symptom of CD was abdominalpain (100%) followed by diarrhea (59%), weight loss (40%), nausea (24%) and vomiting(14%). Fever was present in 22% of CD patients. All patients with UC presented withabdominal pain and bloody diarrhea; 21% of UC patients had fever and 36% had upperGI symptoms. The prevalence of overweight/obesity among patients with IBD was 15%;only 9% of CD patients and none of UC patients had a low BMI (< 5%). Elevated ESR wasfound in 72% of CD patients and 75% of UC patients; 77% of CD patients but only 33%of UC patients had elevated CRP. Among 48 IBD patients that had both CRP and ESR done,23% had normal CRP but elevated ESR; 12.5% had normal ESR but elevated CRP. Altogetherthere was discrepancy between ESR and CRP in 35.5% of patients. Platelets were elevatedin 44% of patients. Low albumin was seen only in 36% of patients and low hemoglobinwas seen in 65% of patients. Normal values of ESR, CRP, albumin, Platelets, and Hemoglobinwere seen only in 8% of patients (1 UC patient and 3 in CD inflammatory phenotype).Conclusions: In our racially diverse pediatric IBD population: 1. Upper GI symptoms werea common presentation in CD as well as UC. 2. We observed high rates of obesity and lowrates of BMI < 5% which is different than the rates reported in the literature. 3. Werecommend screening laboratory tests to include CBC, albumin, ESR, and CRP as it increasesthe yield of abnormal results, alerts physicians to the possibility of inflammatory boweldisease diagnosis and may prevent delay in diagnosis.

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