Cary G. Sauer

Medical radiation exposure in children with inflammatory bowel disease estimates high cumulative doses

Background: Children with inflammatory bowel disease (IBD) undergo imaging using ionizing radiation and may be exposed to high cumulative radiation. We hypothesized that children with IBD have high exposure to radiation from medical imaging. Methods: An Institutional Review Board (IRB)‐approved retrospective chart review from 2002–2008 was performed on all patients with IBD. Radiographic studies performed were recorded and exposure for each study was estimated. Results: A total of 117 children with IBD (86 Crohns disease [CD], 31 ulcerative colitis [UC]) were evaluated. The median current exposure was 15.1 mSv in CD and 7.2 mSv in UC (P = 0.005). Computed tomography (CT) scan and small bowel follow‐through (SBFT) were responsible for 43% and 36% of all radiation exposures, respectively. The rate of radiation was higher in CD compared to UC (4.3 versus 2.2 mSv/yr). In CD, the rate of exposure was highest in the first 3 years of diagnosis (8.2 mSv/yr), and no different between the 3–5 year follow‐up and 5+ year follow‐up groups (3.8 versus 4.3 mSv/yr). Using the annual dose rate in those followed for more than 3 years, an estimated 47 out of 78 (60%) children (40 CD, 7 UC) would exceed 50 mSv by 35 years of age. Conclusions: Radiation exposure from medical imaging is high in a subset of children diagnosed with IBD. Estimation of radiation exposure at age 35 suggests a significant portion of children with IBD will have high radiation exposure in their lifetime. Nonionizing imaging such as magnetic resonance imaging (MRI) and ultrasound should be offered to children with IBD as an alternative to current imaging that employs radiation. Inflamm Bowel Dis 2011

Diverse roles of leptin in the gastrointestinal tract: Modulation of motility, absorption, growth, and inflammation

OBJECTIVE Leptin was discovered in 1994 as a hormone produced by adipose tissue with a modulatory effect on feeding behavior and weight control. Recently, the stomach has been identified as an important source of leptin and growing evidence has shown diverse functions for leptin in the gastrointestinal tract. METHODS Using leptin as a keyword in PubMed, more than 17 000 articles were identified, of which more than 500 articles were related to the role of leptin in the gastrointestinal tract. Available abstracts were reviewed and more than 200 original articles were reviewed in detail. RESULTS The available literature demonstrated that leptin can modulate several important functions of the gastrointestinal tract. Leptin interacts with the vagus nerve and cholecystokinin to delay gastric emptying and has a complex effect on motility of the small bowel. Leptin modulates absorption of macronutrients in the gastrointestinal tract differentially in physiologic and pathologic states. In physiologic states, exogenous leptin has been shown to decrease carbohydrate absorption and to increase the absorption of small peptides by the PepT1 di-/tripeptide transporter. In certain pathologic states, leptin has been shown to increase absorption of carbohydrates, proteins, and fat. Leptin has been shown to be upregulated in the colonic mucosa in patients with inflammatory bowel disease. Leptin stimulates gut mucosal cell proliferation and inhibits apoptosis. These functions have led to speculation about the role of leptin in tumorigenesis in the gastrointestinal tract, which is complicated by the multiple immunoregulatory effects of leptin. CONCLUSION Leptin is an important modulator of major aspects of gastrointestinal tract functions, independent of its more well-described roles in appetite regulation and obesity.

Magnetic Resonance Enterography Healing and Magnetic Resonance Enterography Remission Predicts Improved Outcome in Pediatric Crohn Disease.

Background: Mucosal healing predicts clinical remission and improved outcomes in patients with Crohn disease (CD). Magnetic resonance enterography (MRE) is a noninvasive imaging modality that can assess small and large bowel wall inflammation. Evidence suggests that MRE may be an acceptable alternative to evaluate mucosal healing over endoscopy. Our objective is to determine whether MRE remission predicts clinical remission at follow-up in children with CD. Methods: We performed an institutional review board–approved retrospecitve chart review using our prospectively maintained MRE CD database. Inclusion criteria were all children who underwent an MRE more than 6 months after diagnosis with CD who had follow-up of at least 1 year from imaging. Results: A total of 101 children with CD underwent MRE, a median of 1.3 years from diagnosis with a median follow-up of 2.8 years after MRE. Active inflammation was detected in 65 MRE studies, whereas 36 MRE studies demonstrated MRE remission. A total of 88.9% of children demonstrating MRE remission were in clinical remission at follow-up, whereas only 44.6% of those demonstrating MRE active inflammation achieved clinical remission. Children demonstrating MRE-active inflammation were more likely to have a change in medication (44.6% vs 8.3%) and more likely to undergo surgery (18.5% vs 2.8%). Conclusions: MRE remission is associated with clinical remission at follow-up at least 1 year after MRE. MRE remission was associated with fewer medication changes and fewer surgeries suggesting that, similar to endoscopic remission, MRE remission demonstrates improved outcome. Additional research is needed to confirm that MRE can be used as a surrogate for mucosal healing.

Comparison of magnetic resonance enterography with endoscopy, histopathology, and laboratory evaluation in pediatric crohn disease

Background and Objective: Children with Crohn disease (CD) often undergo cross-sectional imaging during clinical evaluation. Magnetic resonance enterography (MRE) is becoming the preferred radiologic assessment due to the lack of radiation exposure; however, there are few data in children with CD comparing MRE with objective disease measures. The aim of the present study was to compare MRE with endoscopy, histopathology, and laboratory evaluation in children with CD. Methods: We performed an institutional review board–approved query of our prospective CD MRE database, which includes data in children with CD undergoing MRE since 2008. Results: A total of 147 MRE studies were performed in 119 different children with symptomatic CD. Of those, 53 (39.6%) MRE studies were performed at diagnosis to evaluate small bowel disease burden. A total of 117 (79.6%) MRE studies displayed active and/or chronic disease, whereas 30 (20.4%) MRE studies were normal. When compared with normal MRE studies, active inflammation on MRE was associated with a higher mean C-reactive protein (3.6 vs 1.1, P < 0.001), higher erythrocyte sedimentation rate (36 vs 22, P = 0.0.31), higher platelet value (439 vs 352, P = 0.033), and lower albumin (3.4 vs 3.7, P = 0.049). Comparison between MRE and endoscopy demonstrated excellent agreement when ulcers were present, and moderate agreement with histopathology. Conclusions: Active inflammation on MRE is associated with higher C-reactive protein, erythrocyte sedimentation rate, platelets, and lower albumin in children with CD. MRE displays excellent agreement with endoscopic disease described by ulcers but poor agreement with mild mucosal disease described by erythema and friability. The present study adds to a growing body of evidence that MRE provides excellent assessment of inflammation and measures disease activity in CD.

Vitamin D status and bone mineral density in African American children with Crohn disease.

Background: Vitamin D deficiency and low bone mineral density (BMD) are complications of inflammatory bowel disease. Vitamin D deficiency is more prevalent among African Americans compared with whites. There are little data comparing differences in serum 25-hydroxyvitamin D (25OHD) concentrations and BMD between African American and white children with Crohn disease (CD). Methods: We compared serum 25OHD concentrations of African American children with CD (n = 52) to white children with CD (n = 64) and healthy African American controls (n = 40). We also analyzed BMD using dual-energy x-ray absorptiometry results from our pediatric CD population. Results: African American children with CD had lower serum 25OHD concentrations (16.1 [95% confidence interval, CI 14.5–17.9] ng/mL) than whites with CD (22.3 [95% CI 20.2–24.6] ng/mL; P < 0.001). African Americans with CD and controls exhibited similar serum 25OHD concentration (16.1 [95% CI 14.5–17.9] vs 16.3 [95% CI 14.4–18.4] ng/mL; NS). African Americans with CD exhibited no difference in serum 25OHD concentration when controlling for seasonality, disease severity, and surgical history, although serum 25OHD concentration was significantly decreased in overweight children (body mass index ≥85%, P = 0.003). Multiple regression analysis demonstrated that obese African American girls with CD had the lowest serum 25OHD concentrations (9.6 [95% CI 6.8–13.5] ng/mL). BMD was comparable between African American and white children with CD (z score −0.4 ± 0.9 vs −0.7 ± 1.2; NS). Conclusions: African American children with CD are more likely to have vitamin D deficiency compared with white children with CD, but have similar BMD. CD disease severity and history of surgery do not affect serum 25OHD concentrations among African American children with CD. African American children have low serum 25OHD concentrations, independent of CD, compared with white children. Future research should focus on how race affects vitamin D status and BMD in children with CD.

Magnetic resonance enterography in Crohn's disease: techniques, interpretation, and utilization for clinical management.

Crohns disease treatment has improved significantly with the development of immunosuppressive and immunomodulatory agents, while surgery remains an important option in selected patients. However, a relative lag in diagnostics has become apparent with a growing need for the capacity to noninvasively and safely evaluate the tissue changes of Crohns disease within the bowel wall and deeper tissues. We have noted marked technical improvements in magnetic resonance enterography (MRE) and in our understanding of the different facets of Crohns disease that can be elucidated by optimized MRE, in contrast to other diagnostics. This review will provide an integrated understanding of MRE related to other available tests and recommendations for the optimal use of MRE for the clinical management of Crohns disease. We will review the relative strengths and limitations of MRE as applied to clinical evaluation and therapeutic decisions, including the use of the unique capacity to delineate active inflammation and fibrosis in the submucosal and deeper enteric tissues, which is beyond the diagnostic reach of endoscopy and biopsy.

Gastric heterotopia of the rectum.

JPGN Volume 50, N a child is a common s roenterologist. Gastri H ematochezia in ign that precipitates a visit to a gast c heterotopia of the rectum is an uncommon diagnosis but should be considered in a patient with chronic painless rectal bleeding. The true prevalence and risk for malignant transformation is unknown, therefore, removal of the lesion is recommended. We report a case of gastric heterotopia of the rectum in a 5-year-old that was removed with endoscopic ablation and we review the literature.

Common NOD2 risk variants in African Americans with Crohn's disease are due exclusively to recent Caucasian admixture†

Background: Crohns disease (CD) is highly heritable. NOD2 has emerged as the main susceptibility gene among individuals of European ancestry; however, NOD2 does not appear to contribute to CD susceptibility among many non‐European populations. Todays African American (AA) population represents an admixture of West African (80%) and European (20%) ancestry. Since genotype‐based tools are becoming increasingly available for CD, it is important that we validate the risk variants in different populations, such as admixed AAs. Methods: We analyzed the NOD2 variants among admixed AAs (n = 321, 240 with CD and 111 healthy controls [HCs]) and nonadmixed West Africans (n = 40) by genotyping four known disease‐causing NOD variants. We extracted the publicly available 1000 Genomes data on NOD2 variants from 500 subjects of West African origin. Association with disease was evaluated by logistic regression. Results: An association with CD was found for the classical single nucleotide polymorphism (SNP) 1007fs (2.6% CD, 0% HC, P = 0.012); there was no association when the genotypic and allelic frequencies of the risk alleles were compared for SNPs R702W and G908R. No known NOD2 risk alleles were seen in either the West African cohort or in subjects of African ancestry from the 1000 Genomes project. Conclusions: The NOD2 gene is a risk for CD in AAs, although the allele frequencies and the attributable risk are much lower compared with Caucasians. The risk alleles are not seen in the West African population, suggesting that the risk for CD contributed by NOD2 among AAs is due exclusively to recent European admixture. (Inflamm Bowel Dis 2012;)

Consensus recommendations for evaluation, interpretation, and utilization of computed tomography and magnetic resonance enterography in patients with small bowel Crohn’s disease

Computed tomography and magnetic resonance enterography have become routine small bowel imaging tests to evaluate patients with established or suspected Crohns disease, but the interpretation and use of these imaging modalities can vary widely. A shared understanding of imaging findings, nomenclature, and utilization will improve the utility of these imaging techniques to guide treatment options, as well as assess for treatment response and complications. Representatives from the Society of Abdominal Radiology Crohns Disease-Focused Panel, the Society of Pediatric Radiology, the American Gastroenterological Association, and other experts, systematically evaluated evidence for imaging findings associated with small bowel Crohns disease enteric inflammation and established recommendations for the evaluation, interpretation, and use of computed tomography and magnetic resonance enterography in small bowel Crohns disease. This work makes recommendations for imaging findings that indicate small bowel Crohns disease, how inflammatory small bowel Crohns disease and its complications should be described, elucidates potential extra-enteric findings that may be seen at imaging, and recommends that cross-sectional enterography should be performed at diagnosis of Crohns disease and considered for small bowel Crohns disease monitoring paradigms. A useful morphologic construct describing how imaging findings evolve with disease progression and response is described, and standard impressions for radiologic reports that convey meaningful information to gastroenterologists and surgeons are presented. ©2018, RSNA, AGA Institute, and Society of Abdominal Radiology This article is being published jointly in Radiology and Gastroenterology.

Infliximab Optimization Based on Therapeutic Drug Monitoring in Pediatric Inflammatory Bowel Disease

Background: Infliximab (IFX) is an effective treatment for the management of moderate to severe inflammatory bowel disease (IBD). Low-serum IFX levels are associated with the development of antibodies to IFX (ATI), which subsequently associated with clinical relapse and increased morbidity. The primary purpose of this study is to examine the relation between dose and interval to IFX level. Secondary goal is to evaluate the relation between IFX level and ATI in a pediatric IBD population. Methods: We performed a retrospective chart review of all children diagnosed with IBD and treated with IFX at a tertiary care pediatric IBD center. We performed our analysis based on prescribed dosing intervals and rounded dose up to 5 or 10 mg/kg as indicated in clinical practice. Results: Our study included 278 samples from 129 children on IFX. ATI were detected in 37 samples (13.3%). Low IFX levels (<3 &mgr;g/mL) were detected in 37.2% of children receiving IFX. Samples with ATI present had significantly lower levels of IFX than samples in which ATI were not present. For the dose 5 mg/kg, Q6 dosing had significantly higher IFX levels than Q8 dosing (P = 0.009). Higher IFX levels were seen with interval shortening rather than dose escalation. Conclusions: We demonstrate that low IFX levels are associated with development of immunogenicity to IFX as measured by ATI. We demonstrate that interval shortening rather than dose escalation results in higher IFX levels. We suggest that given the high number of IFX levels below 3 &mgr;g/mL in patients, early IFX level evaluation or primary initiation of Q6 week dosing be considered.