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Ulcerative colitis is associated with an increased risk of thromboembolic phenomena. Thrombotic storm defined by the development of multiple thrombi in multiple locations within a short period of time is a rare condition that is potentially life threatening. We present a 14-year-old adolescent boy with an ulcerative colitis flare complicated by Budd-Chiari syndrome and thrombotic storm.

Growth failure remains a common complication of pediatric Crohn's disease (CD) and has been associated with small bowel involvement and need for surgery. We have reported that patients with elevated (≥ 1.6 μg/mL) granulocyte macrophage colony stimulating factor autoantibodies (GM-CSF Ab) are more likely to experience complicated ileal disease requiring surgery. We hypothesized that concurrent GM-CSF Ab and CARD15 risk allele carriage (C15(+) GMAb(+) ) would be associated with growth failure in CD and growth hormone (GH) resistance in murine ileitis.We enrolled 229 pediatric CD patients at two sites and determined CARD15 genotype, serum GM-CSF Ab, and GH binding protein (GHBP), and height (HTz) and weight (WTz) z-scores at diagnosis. Ileitis was induced in card15-deficient mice by GM-CSF neutralization and nonsteroidal antiinflammatory drug (NSAID) exposure. Hepatic GH receptor (GHR) abundance and GH-dependent Stat5 activation were determined by western blot and Igf-I mRNA expression by real-time polymerase chain reaction (PCR).Mean (95% confidence interval [CI]) HTz at diagnosis was reduced to -0.48 (-4.2, 2.3) in C15(+) GMAb(+) patients, compared to -0.07 (-4.9, 3.4) in disease controls (P ≤ 0.05). Circulating GHBP, as a marker for tissue GHR abundance, was reduced in C15(+) GMAb(+) patients. Hepatic GHR abundance, GH induction of Stat5 tyrosine phosphorylation, and Igf-I mRNA expression were reduced in male card15-deficient mice with ileitis due to GM-CSF neutralization and NSAID exposure.Innate dysfunction due to concurrent genetic variation in CARD15 and neutralizing GM-CSF Ab is associated with linear growth failure in pediatric CD, and hepatic GH resistance in murine ileitis.

BACKGROUND: Alterations in intestinal permeability have been implicated in the pathogenesis of Crohn disease (CD). We have reported that granulocyte macrophage-colony-stimulating factor (GM-csF) is required for mucosal barrier function in mice, and elevated neutralizing GM-CsF autoantibodies (Ab) are associated with stricturing ileal disease and surgery in patients with CD. We hypothesized that children with CD with elevated GM-CSF Ab would exhibit increased intestinal permeability. PATIENTS AND METHODS: Subjects were divided into 3 groups: 15 with CD andhigh GM-CSF Ab (≥1.6 μg/mL, GM-CSF Ab Hi), 12 with CD and low GM-CSF Ab (

In the original description of Crohn's disease, the appendix was not believed to be involved in the inflammatory process. Later on, case reports started to appear in publications demonstrating that the appendix could be involved in the inflammatory changes of Crohn's disease, and it could also be the primary or the sole manifestation of the disease. Being that appendectomies are one of the most common procedures performed by pediatric surgeons, the knowledge about this diagnosis, all be it rare, is important. Our aim was to report a case and discuss the results of our literature review in order to elucidate the probability of a pediatric patient subsequently developing full Crohn's disease and the follow up that is indicated in such patients. A 12-year-old male patient presented with a history of chronic abdominal pain (3-4 times per week) for 1 year, crampy in nature, localized in the left lower quadrant, and associated with diarrhea (2 episodes per day). There were no extraintestinal manifestations of Crohn's, such as arthralgia or uveitis. Important family history included two paternal uncles with ulcerative colitis both of whom currently have stomas. The only abnormal laboratory value in our patient was an elevated fecal calprotectin level. An esophagogastroduodenoscopy and colonoscopy were performed and found to be unremarkable except for the cecum where it appeared that an exudate was emanating from the appendiceal orifice. A magnetic resonance enterography was ordered and showed an enlarged enhancing appendix. An exploratory laparoscopy identified an appendix with macroscopic cobblestone or lymphoid reaction that histologically was consistent with Crohn's disease. It appears that the Crohn's appendix is more indolent than Crohn's disease of the ileum or colon, with a recurrence rate in the largest series of 8%. The interval time from diagnosis to recurrence varied from 1 to 48 months with an average of 19 months. Some authors debate the need of follow up at all in those patients, believing that the appendectomy alone is curative in the majority of patients. Others recommend follow up for up to 5 years.

Systemic exposure to lipopolysaccharide (LPS) has been linked to clinical disease activity in adults with inflammatory bowel disease (IBD). We hypothesized that markers of LPS exposure and the acute phase response (APR) would be increased in pediatric IBD patients with growth failure, and that LPS signaling would be required for induction of the APR in murine colitis.Serum markers of LPS exposure, endotoxin core IgA antibody (EndoCAb), and the APR, LPS binding protein (LBP) were quantified in pediatric IBD patients and controls. LBP and cytokine production were determined after administration of trinitrobenzene sulfonic acid (TNBS) enemas to mice with genetic deletion of Toll-Like receptor 4 (TLR4), and wildtype (WT) controls.Serum EndoCAb and LBP were significantly elevated in patients with Crohn's disease (CD), compared to disease controls with ulcerative colitis (UC) and healthy controls (P0.001). This was independent of disease activity or location. CD patients with elevated serum EndoCAb and LBP exhibited linear growth failure which persisted during therapy. Serum LBP increased in WT mice following TNBS administration, in conjunction with increased serum TNF-alpha, IL-6, and IL-10, and expansion of regulatory T-cell numbers. Both the APR and expansion of foxp3+ T cells were abrogated in TLR4-deficient mice, in conjunction with a reduction in acute weight loss.LPS exposure and a persistent APR are associated with growth failure in pediatric CD. LPS signaling is required for the APR in murine colitis. Therapies targeting this pathway may benefit the subset of patients with refractory growth failure.

presence of disabling chronic symptoms, need for immunosuppressive therapy and intestinal resection or perianal surgery. (b) Liege Hospital (Belgium) definition including at least one of the following criteria: development of a complex perianal disease, any colonic resection, more than one small-bowel resection or a definite stoma. (c) a new definition that we proposed including nutritional impairment defined by a BMI or weight or height less than 2SD Z scores and at least one intestinal resection or two perianal surgeries. RESULTS: According to definition (a), the rate of PO was 76%. Independent predictors at diagnosis were L2L3 (Montreal classification) (OR: 3.74 [1.71-8.22]) and nutritional impairment (OR: 2.47 [1.26-4.85]). According to definition (b), the rate of PO was 34% and the only predictive factor was B2B3 behaviour at diagnosis (OR: 3.26[1.77-6.02]). According to definition (c), the rate of PO was 15% and predictors were B2B3 behaviour (OR: 3.42 [1.179.95]), nutritional impairment at diagnosis (OR: 5.35 [1.89-15.16]), and an age between 14 and 17 years at diagnosis (OR: 4.07 [1.44-11.49]). Bootstrap validation is ongoing. CONCLUSION: Using a new descriminant definition, 15% of children developped PO within 5 years after diagnosis. Nutritional impairment and stricturing or penetrating behaviour at diagnosis were predictors of PO as well as an age between 14 and 17 years at diagnosis. If validated, these predictors may be useful to select patients in whom early intensive therapy should be considered.