- Email: [email protected]
Sa1999 Characteristics of Racially Diverse Pediatric Inflammatory Bowel Disease (IBD) Population
18% added an immunomodulator, 10% had dose escalation of their current therapy and 18% had a change within medication class. VCE was abnormal in 94% of those who had change in treatment. VCE revealed more extensive small bowel involvement than concurrent small bowel imaging modalities in 27% (3/11) of patients. Abnormal VCE results was most commonly (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 decreased significantly after change in treatment post VCE (23 vs.15 p=0.004). VCE was able to “rule out” IBD in 94% of those who had suspected IBD, while 50% of patients with presumed UC or IBDU had diagnosis changed to CD. Conclusion: VCE provides an additive clinical benefit in pediatric patients with IBD requiring further small bowel evaluation despite active treatment especially in the face of poor growth. VCE can help “rule out” IBD, as well as help lead to diagnostic reclassification of patients with UC or IC. Though more prospective studies are needed, VCE can be very useful in decision making and monitoring in pediatric IBD.
Conclusion: Transabdominal US is effective in identifying remissive, mild, moderate and severe IBD. These results argue that US is a compelling adjunctive modality for monitoring pediatric inflammatory bowel disease.
The Probiotic VSL#3 in Children With Crohn Disease in Remission Andrew S. Day, Steven T. Leach, Thomas A. Judd, Kashan Baba, Rebecca J. Hill, Daniel A. Lemberg Background and Aims: VSL#3, a probiotic preparation containing 8 bacterial strains at a high concentration, has proven clinical efficacy in the induction and maintenance of remission of ulcerative colitis in children and adults. However, the role of this agent in the maintenance of remission in conjunction with standard therapy has not yet been evaluated in pediatric Crohn disease (CD). The primary aim of this study was to assess the role of VSL#3 in the maintenance of remission of children with CD, whilst secondary end-points included serum and faecal inflammatory markers, growth parameters and quality of life (QOL) scores. Methods: A randomised, double-blind, placebo-controlled study was conducted in children aged between 4 and 18 years with existing diagnosis of CD. Additional inclusion criteria was current remission based upon Pediatric CD Disease Activity Index (PCDAI) scores less than 15. Children were randomised to receive active probiotic (standard dose of 1,800 million organisms daily with adjustment for weight) or placebo for 12 months, with evaluation of length of remission, requirement for rescue therapy, serum and faecal inflammatory markers, growth and quality of life (QOL) scores. Results: Data from 28 children was available for evaluation. Twelve children (10 boys) of average age of 13.3 (SD 3.0) years were randomised 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 inflammatory markers and growth parameters were not different between the groups. QOL scores were not 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 greater at 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 any time points. Levels of the fecal inflammatory marker, S100A12, appeared higher in the placebo group than the probiotic group at months 6, 9 and 12, and indeed approached significance at month 6 (p < 0.055). Conclusions: In this 12 month study in children with CD in remission, high-dose probiotic therapy did not influence the relapse rate when assessed in comparison to standard therapy. However, there was a trend towards decreasing faecal markers of gut inflammation with VSL#3, and such results need to be confirmed in a larger study. In consideration of its beneficial effects on inflammatory and nutritional parameters in pediatric patients with active CD (Day et al, DDW 2012), we hypothesize that better results could be observed in the quiescent phase of the disease if VSL#3 supplementation is started during active disease.
Sa1996 Crohn's Disease Associated NOD2 Variants Show Differential Activation of NFkB in Response to Autosignaling and Muramyl Dipeptide Johan 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 family, member 15) are associated with increased susceptibility to Crohn's disease (CD). These SNPs are thought to disrupt the sensing of bacterial muramyl dipeptide (MDP) at the Cterminus 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 with MDP has not been investigated at low levels of NOD2 expression. Data regarding the linkage disequilibrium (LD) between these CD-associated SNPs are scarce. Methods: NOD2 variant constructs (rs2066842 (SNP5), rs2066844 (SNP8), rs2066845 (SNP12) and rs2066847 (SNP13), SNP5+8, SNP5+12 and SNP5+13) were created by site-directed mutagenesis of a pCMV plasmid containing wild-type N-terminal FLAG-NOD2. NF-kB luciferase assays were performed on HEK293 cells following transient transfection (20hr) with wildtype (WT) and NOD2 variant constructs, titrating NOD2 from 1-100ng/well. The NF-kB luciferase response of NOD2 (1ng)-transfected HEK293 cells to MDP (10microgram/well) was measured. 2way ANOVA and unpaired t-tests were used. By means of Haploview-analysis of sequencing data of the exons and exon-intron boundaries in 24 paediatric Caucasian Crohn's disease patients, we assessed the LD between SNP5 and SNP8, 12 and 13. Results: 2-way ANOVA demonstrated an effect of NOD2 genotype and concentration on auto-signaling at low levels of expression (p<0.0001). This was due to the significant difference of auto-activation between 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 for the MDP-stimulation experiment. MDP stimulation led to a significant increase of NF-kB luciferase 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 in 24 children with CD, showed that LD between SNP5 and the other CD-associated variants is low (r-squared <0.1), in spite of close physical proximity (D' 1.0). Conclusion: Our combined genetic and functional analyses demonstrate that the association of SNP5 with Crohn'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 activation of NF-kB.
Sa1999 Characteristics of Racially Diverse Pediatric Inflammatory Bowel Disease (IBD) Population Gitit Tomer, Yolanda Rivas, John F. Thompson Background: IBD is increasingly recognized in diverse ethnic populations. In the United States, IBD among minorities has not been thoroughly studied and there are scarce data regarding disease presentation and laboratory values. Objective: To characterize the clinical phenotype of racially diverse pediatric IBD population. Methods: A retrospective chart review of patients with IBD who are followed in Pediatric Gastroenterology was performed. Detailed phenotypic information was obtained and biomarkers at diagnosis were recorded, including hemoglobin, 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 with ulcerative 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 minority patients. 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% were hospitalized and only 5% had positive family history of IBD. The mean duration of symptoms before diagnosis was 25 weeks. The most frequent presenting symptom of CD was abdominal pain (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 with abdominal pain and bloody diarrhea; 21% of UC patients had fever and 36% had upper GI 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 was found 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. Altogether there was discrepancy between ESR and CRP in 35.5% of patients. Platelets were elevated in 44% of patients. Low albumin was seen only in 36% of patients and low hemoglobin was seen in 65% of patients. Normal values of ESR, CRP, albumin, Platelets, and Hemoglobin were 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 were a common presentation in CD as well as UC. 2. We observed high rates of obesity and low rates of BMI < 5% which is different than the rates reported in the literature. 3. We recommend screening laboratory tests to include CBC, albumin, ESR, and CRP as it increases the yield of abnormal results, alerts physicians to the possibility of inflammatory bowel disease diagnosis and may prevent delay in diagnosis.
Sa1997 Monitoring Crohns Disease Activity in Children: A Retrospective Comparison of Transabdominal Ultrasound and Ileocolonoscopy Kerri 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 children require general anesthetic for endoscopy and they are particularly vulnerable to potential adverse effects of ionizing radiation, present with computed tomography. Routine access to other modalities, such as magnetic resonance, is limited. Therefore, safe, tolerable, and accessible means of evaluating inflammatory activity in IBD is key to direct medical management. Data to support the use of US in monitoring pediatric IBD is limited. Objective: To compare sonographic and colonoscope features of inflammation in a group of pediatric IBD patients. Methods: This is a University of Calgary Ethics Board approved study. IBD patients were from an established database of children with IBD and cross-referenced with a radiology database. Luminal sonographic images and endoscopic findings from pediatric patients with IBD and controls were reviewed. Only patients having ileocolonoscopy within 3 months of ultrasound were included. Inflammatory US parameters included bowel wall thickness, presence of mesenteric inflammatory fat, lymphadenopathy, and hyperemia (detectable color Doppler signal within the bowel wall). The Mann-Whitney U-Test was utilized to compare ultrasound with endoscopic finding, the Signed Rank test was used to assess the relationship between endoscopic and US disease severity and T-tests were used to compare US parameters in IBD patients versus control patients. Results: This is the largest retrospective pediatric US study known to date. A total of 103 patients were evaluated: 72.8% (n=75) had confirmed IBD, 80% (n=60) had Crohns disease, 17.3% (n=13) had ulcerative colitis, 2.7% (n=2) had indeterminant colitis and 27.1% (n=28) were healthy. 17.4% of patients were treated with Biologics, 53.3% with immune modulators and 30.7% with corticosteroids. 20% (n=15) of patients 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, bowel wall thickness, hyperemia, number of lymph nodes or presence of inflammatory fat. Alternatively, 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
AGA Abstracts
Sa1998
Conclusion: Transabdominal US is effective in identifying remissive, mild, moderate and severe IBD. These results argue that US is a compelling adjunctive modality for monitoring pediatric inflammatory bowel disease.
The Probiotic VSL#3 in Children With Crohn Disease in Remission Andrew S. Day, Steven T. Leach, Thomas A. Judd, Kashan Baba, Rebecca J. Hill, Daniel A. Lemberg Background and Aims: VSL#3, a probiotic preparation containing 8 bacterial strains at a high concentration, has proven clinical efficacy in the induction and maintenance of remission of ulcerative colitis in children and adults. However, the role of this agent in the maintenance of remission in conjunction with standard therapy has not yet been evaluated in pediatric Crohn disease (CD). The primary aim of this study was to assess the role of VSL#3 in the maintenance of remission of children with CD, whilst secondary end-points included serum and faecal inflammatory markers, growth parameters and quality of life (QOL) scores. Methods: A randomised, double-blind, placebo-controlled study was conducted in children aged between 4 and 18 years with existing diagnosis of CD. Additional inclusion criteria was current remission based upon Pediatric CD Disease Activity Index (PCDAI) scores less than 15. Children were randomised to receive active probiotic (standard dose of 1,800 million organisms daily with adjustment for weight) or placebo for 12 months, with evaluation of length of remission, requirement for rescue therapy, serum and faecal inflammatory markers, growth and quality of life (QOL) scores. Results: Data from 28 children was available for evaluation. Twelve children (10 boys) of average age of 13.3 (SD 3.0) years were randomised 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 inflammatory markers and growth parameters were not different between the groups. QOL scores were not 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 greater at 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 any time points. Levels of the fecal inflammatory marker, S100A12, appeared higher in the placebo group than the probiotic group at months 6, 9 and 12, and indeed approached significance at month 6 (p < 0.055). Conclusions: In this 12 month study in children with CD in remission, high-dose probiotic therapy did not influence the relapse rate when assessed in comparison to standard therapy. However, there was a trend towards decreasing faecal markers of gut inflammation with VSL#3, and such results need to be confirmed in a larger study. In consideration of its beneficial effects on inflammatory and nutritional parameters in pediatric patients with active CD (Day et al, DDW 2012), we hypothesize that better results could be observed in the quiescent phase of the disease if VSL#3 supplementation is started during active disease.
Sa1996 Crohn's Disease Associated NOD2 Variants Show Differential Activation of NFkB in Response to Autosignaling and Muramyl Dipeptide Johan 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 family, member 15) are associated with increased susceptibility to Crohn's disease (CD). These SNPs are thought to disrupt the sensing of bacterial muramyl dipeptide (MDP) at the Cterminus 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 with MDP has not been investigated at low levels of NOD2 expression. Data regarding the linkage disequilibrium (LD) between these CD-associated SNPs are scarce. Methods: NOD2 variant constructs (rs2066842 (SNP5), rs2066844 (SNP8), rs2066845 (SNP12) and rs2066847 (SNP13), SNP5+8, SNP5+12 and SNP5+13) were created by site-directed mutagenesis of a pCMV plasmid containing wild-type N-terminal FLAG-NOD2. NF-kB luciferase assays were performed on HEK293 cells following transient transfection (20hr) with wildtype (WT) and NOD2 variant constructs, titrating NOD2 from 1-100ng/well. The NF-kB luciferase response of NOD2 (1ng)-transfected HEK293 cells to MDP (10microgram/well) was measured. 2way ANOVA and unpaired t-tests were used. By means of Haploview-analysis of sequencing data of the exons and exon-intron boundaries in 24 paediatric Caucasian Crohn's disease patients, we assessed the LD between SNP5 and SNP8, 12 and 13. Results: 2-way ANOVA demonstrated an effect of NOD2 genotype and concentration on auto-signaling at low levels of expression (p<0.0001). This was due to the significant difference of auto-activation between 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 for the MDP-stimulation experiment. MDP stimulation led to a significant increase of NF-kB luciferase 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 in 24 children with CD, showed that LD between SNP5 and the other CD-associated variants is low (r-squared <0.1), in spite of close physical proximity (D' 1.0). Conclusion: Our combined genetic and functional analyses demonstrate that the association of SNP5 with Crohn'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 activation of NF-kB.
Sa1999 Characteristics of Racially Diverse Pediatric Inflammatory Bowel Disease (IBD) Population Gitit Tomer, Yolanda Rivas, John F. Thompson Background: IBD is increasingly recognized in diverse ethnic populations. In the United States, IBD among minorities has not been thoroughly studied and there are scarce data regarding disease presentation and laboratory values. Objective: To characterize the clinical phenotype of racially diverse pediatric IBD population. Methods: A retrospective chart review of patients with IBD who are followed in Pediatric Gastroenterology was performed. Detailed phenotypic information was obtained and biomarkers at diagnosis were recorded, including hemoglobin, 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 with ulcerative 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 minority patients. 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% were hospitalized and only 5% had positive family history of IBD. The mean duration of symptoms before diagnosis was 25 weeks. The most frequent presenting symptom of CD was abdominal pain (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 with abdominal pain and bloody diarrhea; 21% of UC patients had fever and 36% had upper GI 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 was found 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. Altogether there was discrepancy between ESR and CRP in 35.5% of patients. Platelets were elevated in 44% of patients. Low albumin was seen only in 36% of patients and low hemoglobin was seen in 65% of patients. Normal values of ESR, CRP, albumin, Platelets, and Hemoglobin were 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 were a common presentation in CD as well as UC. 2. We observed high rates of obesity and low rates of BMI < 5% which is different than the rates reported in the literature. 3. We recommend screening laboratory tests to include CBC, albumin, ESR, and CRP as it increases the yield of abnormal results, alerts physicians to the possibility of inflammatory bowel disease diagnosis and may prevent delay in diagnosis.
Sa1997 Monitoring Crohns Disease Activity in Children: A Retrospective Comparison of Transabdominal Ultrasound and Ileocolonoscopy Kerri 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 children require general anesthetic for endoscopy and they are particularly vulnerable to potential adverse effects of ionizing radiation, present with computed tomography. Routine access to other modalities, such as magnetic resonance, is limited. Therefore, safe, tolerable, and accessible means of evaluating inflammatory activity in IBD is key to direct medical management. Data to support the use of US in monitoring pediatric IBD is limited. Objective: To compare sonographic and colonoscope features of inflammation in a group of pediatric IBD patients. Methods: This is a University of Calgary Ethics Board approved study. IBD patients were from an established database of children with IBD and cross-referenced with a radiology database. Luminal sonographic images and endoscopic findings from pediatric patients with IBD and controls were reviewed. Only patients having ileocolonoscopy within 3 months of ultrasound were included. Inflammatory US parameters included bowel wall thickness, presence of mesenteric inflammatory fat, lymphadenopathy, and hyperemia (detectable color Doppler signal within the bowel wall). The Mann-Whitney U-Test was utilized to compare ultrasound with endoscopic finding, the Signed Rank test was used to assess the relationship between endoscopic and US disease severity and T-tests were used to compare US parameters in IBD patients versus control patients. Results: This is the largest retrospective pediatric US study known to date. A total of 103 patients were evaluated: 72.8% (n=75) had confirmed IBD, 80% (n=60) had Crohns disease, 17.3% (n=13) had ulcerative colitis, 2.7% (n=2) had indeterminant colitis and 27.1% (n=28) were healthy. 17.4% of patients were treated with Biologics, 53.3% with immune modulators and 30.7% with corticosteroids. 20% (n=15) of patients 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, bowel wall thickness, hyperemia, number of lymph nodes or presence of inflammatory fat. Alternatively, 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
AGA Abstracts
Sa1998