The Crohn's Disease-Health Index: Development and Evaluation of a Novel Outcome Measure.

Objective: We sought to develop and validate the Crohn's Disease-Health Index (CD-HI), a disease-specific, patient-reported outcome measure that serially measures Crohn's disease (CD) symptomatic burden in adults with CD.

Background: As therapeutic interventions are tested among patients with CD, responsive outcome measures are needed to track disease progression and therapeutic gain during clinical trials.

Patients And Methods: We conducted a national cross-sectional study of individuals with CD to identify the most prevalent and impactful symptoms of CD.

Patient-Reported Impact of Symptoms in Crohn's Disease.

Introduction: Patients with Crohn's disease (CD) experience a variety of symptoms that significantly affect their lives. In this study, we (i) ascertain the most prevalent and impactful symptoms in CD and (ii) identify modifying factors that are associated with a higher disease burden in CD.

Methods: We conducted semistructured interviews with adult participants with CD to determine what issues have the greatest impact on their lives.

P047 The Crohn's Disease-Health Index (CD-HI): Development and Validation of a Novel, Disease-Specific Patient Reported Outcome Measure for Clinical Trials.

Background: In preparation for upcoming clinical trials involving patients with Crohn's disease (CD), we examine the validity, reliability and usability of the Crohn's Disease-Health Index (CD-HI). The CD-HI is a multifaceted, disease-specific patient reported outcome measure (PROM) designed to measure CD symptomatic disease burden during clinical trials. As promising therapeutic interventions are being tested among CD patients, there is a clear need for researchers to have access to a valid, sensitive, and reliable patient reported outcome tool to track disease burden.

Late-Onset Posttransplant Lymphoproliferative Disorder Results in Jejunal Stricture Managed with Endoscopic Dilation.

Background: Late-onset posttransplant lymphoproliferative disorder (PTLD) after orthotopic heart transplantation is rare. . We present a rare diagnosis of small bowel stricture caused by healed lymphomatous ulcers in a patient with orthotopic heart transplantation and PTLD diagnosed 25 years after initial transplantation.

Assessment of systemic genetic damage in pediatric inflammatory bowel disease.

The etiology of distal site cancers in inflammatory bowel disease (IBD) is not well understood and requires further study. We investigated whether pediatric IBD patients' blood cells exhibit elevated levels of genomic damage by measuring the frequency of mutant phenotype (CD59-/CD55-) reticulocytes (MUT RET) as a reporter of PIG-A mutation, and the frequency of micronucleated reticulocytes (MN-RET) as an indicator of chromosomal damage. IBD patients (n = 18 new-onset disease, 46 established disease) were compared to age-matched controls (constipation or irritable bowel syndrome patients from the same clinic, n = 30) and young healthy adults age 19-24 (n = 25).

Human blood PIG-A mutation and micronucleated reticulocyte flow cytometric assays: Method optimization and evaluation of intra- and inter-subject variation.

We previously described flow cytometry-based methods for scoring the incidence of micronucleated reticulocytes (MN-RET) and PIG-A mutant phenotype reticulocytes (MUT RET) in rodent and human blood samples. The current report describes important methodological improvements for human blood analyses, including immunomagnetic enrichment of CD71-positive reticulocytes prior to MN-RET scoring, and procedures for storing frozen blood for later PIG-A analysis. Technical replicate variability in MN-RET and MUT RET frequencies based on blood specimens from 14 subjects, intra-subject variability based on serial blood draws from 6 subjects, and inter-subject variation based on up to 344 subjects age 0 to 73 years were quantified.

Dextran sulfate sodium mouse model of inflammatory bowel disease evaluated for systemic genotoxicity via blood micronucleus and Pig-a gene mutation assays.

Inflammatory bowel disease (IBD) is an important risk factor for gastrointestinal cancers. Inflammation and other carcinogenesis-related effects at distal, tissue-specific sites require further study. In order to better understand if systemic genotoxicity is associated with IBD, we exposed mice to dextran sulfate sodium salt (DSS) and measured the incidence of micronucleated cells (MN) and Pig-a mutant phenotype cells in blood erythrocyte populations.

Assessing the Validity of Adult-derived Prognostic Models for Primary Sclerosing Cholangitis Outcomes in Children.

Background: Natural history models for primary sclerosing cholangitis (PSC) are derived from adult patient data, but have never been validated in children. It is unclear how accurate such models are for children with PSC.

Methods: We utilized the pediatric PSC consortium database to assess the Revised Mayo Clinic, Amsterdam-Oxford, and Boberg models.

Ursodeoxycholic Acid Therapy in Pediatric Primary Sclerosing Cholangitis: Predictors of Gamma Glutamyltransferase Normalization and Favorable Clinical Course.

Objective: To investigate patient factors predictive of gamma glutamyltransferase (GGT) normalization following ursodeoxycholic acid (UDCA) therapy in children with primary sclerosing cholangitis.

Study Design: We retrospectively reviewed patient records at 46 centers. We included patients with a baseline serum GGT level ≥50 IU/L at diagnosis of primary sclerosing cholangitis who initiated UDCA therapy within 1 month and continued therapy for at least 1 year.

Gamma Glutamyltransferase Reduction Is Associated With Favorable Outcomes in Pediatric Primary Sclerosing Cholangitis.

Adverse clinical events in primary sclerosing cholangitis (PSC) happen too slowly to capture during clinical trials. Surrogate endpoints are needed, but no such validated endpoints exist for children with PSC. We evaluated the association between gamma glutamyltransferase (GGT) reduction and long-term outcomes in pediatric PSC patients.

Unexpectedly High Prevalence of Cystoisospora belli Infection in Acalculous Gallbladders of Immunocompetent Patients.

Objectives: Indications for cholecystectomy have changed dramatically over the past three decades. Cystoisospora belli has been reported in cholecystectomy specimens of immunocompetent patients. The present study was designed to determine the prevalence and clinical association of C belli in the gallbladder.

The natural history of primary sclerosing cholangitis in 781 children: A multicenter, international collaboration.

Unlabelled: There are limited data on the natural history of primary sclerosing cholangitis (PSC) in children. We aimed to describe the disease characteristics and long-term outcomes of pediatric PSC. We retrospectively collected all pediatric PSC cases from 36 participating institutions and conducted a survival analysis from the date of PSC diagnosis to dates of diagnosis of portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or death.

Hepatic Issues and Complications Associated With Inflammatory Bowel Disease: A Clinical Report From the NASPGHAN Inflammatory Bowel Disease and Hepatology Committees.

Hepatobiliary disorders are common in patients with inflammatory bowel disease (IBD), and persistent abnormal liver function tests are found in approximately 20% to 30% of individuals with IBD. In most cases, the cause of these elevations will fall into 1 of 3 main categories. They can be as a result of extraintestinal manifestations of the disease process, related to medication toxicity, or the result of an underlying primary hepatic disorder unrelated to IBD.

Sustained improvement in health-related quality of life measures in patients with inflammatory bowel disease receiving prolonged anti-tumor necrosis factor therapy.

Objective: The aim of this study was to determine whether the effects of prolonged therapy (≥1 year) with anti-tumor necrosis factor (TNF) agents were sustained on the health-related quality of life (HRQoL) in patients with inflammatory bowel disease (IBD).

Methods: A cross-sectional survey of patients with IBD who were treated with anti-TNF agents was performed. Results of the validated HRQoL measures (inflammatory bowel disease questionnaire [IBDQ], EuroQoL-5 dimensions [EQ-5D], health status visual analogue scale [VAS] and the Zung self-rating depression scale) were recorded and compared between patients treated with anti-TNF agents for <1 year and ≥1 year.

Neither direct nor developmental exposure to bisphenol A alters the severity of experimental inflammatory colitis in mice.

Bisphenol A (BPA) is a high production volume endocrine disrupting chemical that is widely used in many consumer products and prevalent in human biological fluids. Recent studies suggest that BPA is active even at low levels, raising concern about its potential harm to human health. Given that the main route of exposure to BPA is oral, via the consumption of BPA-tainted foods and beverages, intestinal tissues could be particularly vulnerable to BPA-induced changes.

Mitigation effect of an FGF-2 peptide on acute gastrointestinal syndrome after high-dose ionizing radiation.

Purpose: Acute gastrointestinal syndrome (AGS) resulting from ionizing radiation causes death within 7 days. Currently, no satisfactory agent exists for mitigation of AGS. A peptide derived from the receptor binding domain of fibroblast growth factor 2 (FGF-P) was synthesized and its mitigation effect on AGS was examined.

Selegiline shortage: Causes and costs of a generic drug shortage.

Background: In September 2007, shortages of generic selegiline occurred, forcing patients to either switch to more expensive alternatives or forego treatment. We sought to evaluate prescription trends of generic selegiline and to quantify the economic impact of any resulting drug substitution of more expensive alternatives.

Methods: We analyzed proprietary data from IMS Health on monthly prescriptions in the United States for selegiline and potential substitutes from February 2002 through December 2007.

Characterization of K-ras gene mutations in association with mucinous hypersecretion in intraductal papillary-mucinous neoplasms.

Background/purpose: Intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas have a favorable prognosis. However, invasive ductal carcinomas of the pancreas show a rapid progression. The aim of this study was to investigate gene mutations in pure pancreatic juice from IPMN patients and to define these genetic mutations in relation to the histopathological and clinical features of IPMNs.

Mucosal T-cell immunoregulation varies in early and late inflammatory bowel disease.

Background And Aims: Crohn's disease is a life-long form of inflammatory bowel disease (IBD) mediated by mucosal immune abnormalities. Understanding of the pathogenesis is limited because it is based on data from adults with chronic Crohn's disease. We investigated mucosal T-cell immunoregulatory events in children with early Crohn's disease.

Repertoire of the alpha beta T-cell receptor in the intestine.

The majority of T cells in the human and mouse intestine express the T-cell receptor (TCR) as an alphabeta heterodimer on their cell surface. As the major recognition element of antigens in the context of major histocompatibility complex-derived proteins, an examination of the structure of the alpha beta TCR in intestines has provided significant insights into the potential function of these cells and the major determinants that drive their selection. Studies in the human intestine have shown that the repertoires of intraepithelial lymphocytes (IELs), and likely lamina propria lymphocytes, are polyclonal before and shortly after birth, with the repertoire becoming oligoclonal in adults.

PPARgamma inhibitors reduce tubulin protein levels by a PPARgamma, PPARdelta and proteasome-independent mechanism, resulting in cell cycle arrest, apoptosis and reduced metastasis of colorectal carcinoma cells.

The nuclear transcription factor peroxisome proliferator-activated receptor-gamma (PPARgamma) has been identified as an important therapeutic target in murine models of colorectal cancer (CRC). To examine whether PPARgamma inhibition has therapeutic effects in late-stage CRC, the effects of PPARgamma inhibitors on CRC cell survival were examined in CRC cell lines and a murine CRC model. Low doses (0.

Anti-Saccharomyces cerevisiae antibodies are associated with the development of postoperative fistulas following ileal pouch-anal anastomosis.

Although serologic testing for perinuclear antineutrophil cytoplasmic antibodies (pANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) is reportedly useful in distinguishing ulcerative colitis (UC) from Crohn's disease (CD), there are few and conflicting reports assessing their utility in predicting postoperative complications after ileal pouch-anal anastomosis (IPAA). We examined the associations between postoperative complications such as pouchitis or fistulas and pANCA and ASCA antibodies in a group of patients who underwent IPAA for UC. We conducted a retrospective chart review of 34 patients initially diagnosed with UC (four of these patients had a diagnosis of indeterminate colitis) who underwent IPAA by a single surgeon, and who had pANCA and ASCA antibody levels measured during their clinical course.