Randomised clinical trial: individualised vs. weight-based dosing of azathioprine in Crohn's disease

Azathioprine (AZA), a pro-drug metabolized to the active metabolites 6-thioguanine nucleotides (6TGN), is a steroid-sparing therapy for Crohn’s disease (CD). This trial investigated whether AZA therapy is optimized by individualized dosing based on thiopurine methyltransferase (TPMT) activity and 6TGN concentrations

Race and Inflammatory Bowel Disease in an Urban Healthcare System

Inflammatory bowel disease (IBD) is increasingly common among non-Caucasian populations, but interracial differences in disease characteristics and management are not well-characterized. We tested the hypothesis that disease characteristics and management vary by race among IBD patients in an ethnically diverse healthcare system. A retrospective study of the safety net healthcare system of San Francisco, CA, from 1996 to 2009 was undertaken. Patient records with International Classification of Diseases, 9th Revision (ICD9) codes 555.xx, 556.xx, and 558.xx were reviewed. Adult patients with confirmed IBD diagnoses were included. Interracial variations in disease characteristics and management were assessed broadly; focused between-race comparisons identified specific differences. The 228 subjects included 77 (33.4%) with Crohn’s disease (CD), 150 (65.8%) with ulcerative colitis, and 1 (0.4%) with IBD, type unclassified. The race distribution included 105 (46.1%) white, 34 (14.9%) black, 35 (15.4%) Hispanic, and 51 (22.4%) Asian subjects. Asians and Hispanics were diagnosed at older ages (41.0 and 37.1 years, respectively) and had shorter disease durations (5.4 and 5.2 years, respectively) than whites (30.5 years at diagnosis and 8.6 years duration, P < 0.05) and blacks (31.7 years at diagnosis and 12.1 years duration, P < 0.05). CD was more common among blacks (50% of subjects) than Asians (25.5% of subjects, P = 0.015). The Montreal classification of IBD was similar among races. Hispanics were less likely than others to be treated with 5-aminosalicylates (5-ASA), immunomodulators, and steroids. Medical and surgical management was otherwise similar among races. Modest race-based differences in IBD characteristics exist in this racially diverse healthcare system, but the management of IBD is similar among race groups

NOD2 Mutations and Anti-Saccharomyces cerevisiae Antibodies Are Risk Factors for Crohn's Disease in African Americans

NOD2 mutations and anti-Saccharomyces cerevisiae antibodies (ASCA) are associated with Crohn’s disease (CD), ileal involvement and complicated disease behavior in whites. ASCA and the three common NOD2 mutations have not been assessed in African American (AA) adults with CD

Mucosal Healing in Ulcerative Colitis: A Comprehensive Review

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by periods of remission and periods of relapse. Patients often present with symptoms such as rectal bleeding, diarrhea and weight loss, and may require hospitalization and even colectomy. Long-term complications of UC include decreased quality of life and productivity and an increased risk of colorectal cancer. Mucosal healing (MH) has gained progressive importance in the management of UC patients. In this article, we review the endoscopic findings that define both mucosal injury and MH, and the strengths and limitations of the scoring systems currently available in clinical practice. The basic mechanisms behind colonic injury and MH are covered, highlighting the pathways through which different drugs exert their effect towards reducing inflammation and promoting epithelial repair. A comprehensive review of the evidence for approved drugs for UC to achieve and maintain MH is provided, including a section on the pharmacokinetics of anti-tumor necrosis factor (TNF)-alpha drugs. Currently approved drugs with proven efficacy in achieving MH in UC include salicylates, corticosteroids (induction only), calcineurin inhibitors (induction only), thiopurines, vedolizumab and anti-TNF alpha drugs (infliximab, adalimumab, and golimumab). MH is of crucial relevance in the outcomes of UC, resulting in lower incidences of clinical relapse, the need for hospitalization and surgery, as well as reduced rates of dysplasia and colorectal cancer. Finally, we present recent evidence towards the need for a more strict definition of complete MH as the preferred endpoint for UC patients, using a combination of both endoscopic and histological findings.info:eu-repo/semantics/publishedVersio

Host Genes Related to Paneth Cells and Xenobiotic Metabolism Are Associated with Shifts in Human Ileum-Associated Microbial Composition

The aim of this study was to integrate human clinical, genotype, mRNA microarray and 16 S rRNA sequence data collected on 84 subjects with ileal Crohn’s disease, ulcerative colitis or control patients without inflammatory bowel diseases in order to interrogate how host-microbial interactions are perturbed in inflammatory bowel diseases (IBD). Ex-vivo ileal mucosal biopsies were collected from the disease unaffected proximal margin of the ileum resected from patients who were undergoing initial intestinal surgery. Both RNA and DNA were extracted from the mucosal biopsy samples. Patients were genotyped for the three major NOD2 variants (Leufs1007, R702W, and G908R) and the ATG16L1T300A variant. Whole human genome mRNA expression profiles were generated using Agilent microarrays. Microbial composition profiles were determined by 454 pyrosequencing of the V3–V5 hypervariable region of the bacterial 16 S rRNA gene. The results of permutation based multivariate analysis of variance and covariance (MANCOVA) support the hypothesis that host mucosal Paneth cell and xenobiotic metabolism genes play an important role in host microbial interactions

Contribution of higher risk genes and European admixture to Crohnʼs disease in African Americans:

African Americans (AA) are an admixed population of West African (WA) and European ancestry (EA). Crohn's disease (CD) susceptibility genes have not been established. We therefore evaluated the contribution of European admixture and major established risk genes to AA CD

JPN Guidelines for the management of acute pancreatitis: epidemiology, etiology, natural history, and outcome predictors in acute pancreatitis

Acute pancreatitis is a common disease with an annual incidence of between 5 and 80 people per 100 000 of the population. The two major etiological factors responsible for acute pancreatitis are alcohol and cholelithiasis (gallstones). The proportion of patients with pancreatitis caused by alcohol or gallstones varies markedly in different countries and regions. The incidence of acute alcoholic pancreatitis is considered to be associated with high alcohol consumption. Although the incidence of alcoholic pancreatitis is much higher in men than in women, there is no difference in sexes in the risk involved after adjusting for alcohol intake. Other risk factors include endoscopic retrograde cholangiopancreatography, surgery, therapeutic drugs, HIV infection, hyperlipidemia, and biliary tract anomalies. Idiopathic acute pancreatitis is defined as acute pancreatitis in which the etiological factor cannot be specified. However, several studies have suggested that this entity includes cases caused by other specific disorders such as microlithiasis. Acute pancreatitis is a potentially fatal disease with an overall mortality of 2.1%–7.8%. The outcome of acute pancreatitis is determined by two factors that reflect the severity of the illness: organ failure and pancreatic necrosis. About half of the deaths in patients with acute pancreatitis occur within the first 1–2 weeks and are mainly attributable to multiple organ dysfunction syndrome (MODS). Depending on patient selection, necrotizing pancreatitis develops in approximately 10%–20% of patients and the mortality is high, ranging from 14% to 25% of these patients. Infected pancreatic necrosis develops in 30%–40% of patients with necrotizing pancreatitis and the incidence of MODS in such patients is high. The recurrence rate of acute pancreatitis is relatively high: almost half the patients with acute alcoholic pancreatitis experience a recurrence. When the gallstones are not treated, the risk of recurrence in gallstone pancreatitis ranges from 32% to 61%. After recovering from acute pancreatitis, about one-third to one-half of acute pancreatitis patients develop functional disorders, such as diabetes mellitus and fatty stool; the incidence of chronic pancreatitis after acute pancreatitis ranges from 3% to 13%. Nevertheless, many reports have shown that most patients who recover from acute pancreatitis regain good general health and return to their usual daily routine. Some authors have emphasized that endocrine function disorders are a common complication after severe acute pancreatitis has been treated by pancreatic resection

G.: A Meta Registration Framework for Lesion Matching

Abstract. A variety of pixel and feature based methods have been proposed for registering multiple views of anatomy visible in studies obtained using diagnostic, minimally invasive imaging. A given registration method may outperform another depending on anatomical variations, imaging conditions, and imaging sensor performance, and it is often difficult a priori to determine the best registration method for a particular application. To address this problem, we propose a registration framework that pools the results of multiple registration methods using a decision function for validating registrations. We refer to this as meta registration. We demonstrate that our framework outperforms several individual registration methods on the task of registering multiple views of Crohn's disease lesions sampled from a Capsule Endoscopy (CE) study database. We also report on preliminary work on assessing the quality of registrations obtained, and the possibility of using such assessment in the registration framework