摘要： Nodular regenerative hyperplasia (NRH) is a poorly understood liver condition, which is increasingly recognized in thiopurine-treated patients with inflammatory bowel disease (IBD).1 It is difficult to establish an optimal approach to NRH patients, because its manifestations are highly variable (from asymptomatic to symptoms of noncirrhotic portal hypertension [NCPH]) and the prognosis is unknown.2 The aim of this study was to identify NRH cases in IBD patients treated with azathioprine, mercaptopurine, and/or thioguanine, and to describe its clinical course.

关键词： Intestinal Diseases   DING   Patients   aluminium   Subset   Venous Thromboembolism   Inflammatory Bowel Diseases   letter  

摘要： Linked Content This article is linked to Chu et al and Ding et al papers. To view these articles, visit and .

关键词： Toll-like receptor (TLR)   Gene polymorphisms   Inflammatory bowel disease (IBD)   Crohn's disease (CD)   Ulcerative colitis (UC)   Meta-analysis  

摘要： Recently, the roles of toll-like receptor (TLR) polymorphisms in inflammatory bowel disease (IBD) were intensively explored, with conflicting results. Therefore, we performed this study to better assess the relationship between TLR polymorphisms and the risk of IBD. Eligible studies were searched in PubMed, Medline, Embase, and Web of Science. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate associations between TLR polymorphisms and IBD. Significant associations with the risk of IBD were detected for the TLR1 rs5743611, TLR4 rs4986790, TLR4 rs4986791, and TLR6 rs5743810 polymorphisms in overall analyses. Further subgroup analyses according to ethnicity of participants revealed that the TLR1 rs5743611, TLR4 rs4986790, TLR4 rs4986791, TLR6 rs5743810, and TLR9 rs352140 polymorphisms were significantly associated with the risk of IBD in Caucasians. Moreover, the TLR4 rs4986790 polymorphism was significantly correlated with the risk of IBD in West Asians, while the TLR9 rs352140 polymorphism was significantly associated with the risk of IBD in Africans. When we stratified available data according to type of disease, we found similar positive results for TLR1 rs5743611, TLR4 rs4986790, TLR4 rs4986791, and TLR6 rs5743810 polymorphisms. Our findings indicate that TLR1 rs5743611, TLR4 rs4986790, TLR4 rs4986791, TLR6 rs5743810, and TLR9 rs352140 polymorphisms may serve as genetic biomarkers of IBD in certain ethnicities. However, further well-designed studies are still warranted to confirm our findings.

关键词： Disease genetics   DNA sequencing   Genetic association study   Medical genomics  

摘要： In the United States, approximately 5% of individuals with inflammatory bowel disease (IBD) are younger than 20 years old. Studies of pediatric cohorts can provide unique insights into genetic architecture of IBD, which includes Crohn's disease (CD) and ulcerative colitis (UC). Large genome-wide association studies have found more than 200 IBD-associated loci but explain a minority of disease variance for CD and UC. We sought to characterize the contribution of rare variants to disease development, comparing exome sequencing of 368 pediatric IBD patients to publicly available exome sequencing (dbGaP) and aggregate frequency data (ExAC). Using dbGaP data, we performed logistic regression for common variants and optimal unified association tests (SKAT-O) for rare, likely-deleterious variants. We further compared rare variants to ExAC counts with Fisher's exact tests. We did pathway enrichment analysis on the most significant genes from each comparison. Many variants overlapped with known IBD-associated genes (e.g. NOD2). Rare variants were enriched in CD-associated loci (p = 0.009) and showed suggestive enrichment in neutrophil function genes (p = 0.05). Pathway enrichment implicated immune-related pathways, especially cell killing and apoptosis. Variants in extracellular matrix genes also emerged as an important theme in our analysis.

关键词： Colon   Crohn's disease   Histology   Inflammatory bowel diseases   Plasma cells   TNF alpha   Ulcerative colitis  

摘要： Background: Although antitumor necrosis factor alfa (TNF alpha) agents are widely used to treat patients with inflammatory bowel diseases (IBD) - both Crohn's disease (CD) and ulcerative colitis (UC) - there is still some uncertainty in the cell type expressing TNF alpha in human ileo-colonic segments. Aims: We investigated the immunohistochemical (IHC) expression of TNF alpha in the ileo-colonic segments of patients with both active CD and UC, to establish its anatomic and cellular localization in the inflamed sites. Our aim was to identify patients potentially resistant to anti TNF alpha agents. Patients and methods: Ileo-colonic slides of complete histological mapping of patients with CD and UC before any treatment was started were obtained, and serial sections assessed for TNF alpha expression, together with IHC markers for lymphocytes, macrophages, and plasma cells. Results: TNF alpha was expressed in almost all inflamed segments of IBD patients, albeit with different strength, and was present, in addition to lymphocytes and, to a lesser extent, to macrophages, in plasma cells, where it had a strong positivity, as also demonstrated by colocalization of specific IHC staining. The expression of TNF alpha was mostly focal in CD patients and more diffuse in UC patients, likely due to the different patterns of inflammation (transmural and mucosal) of the two entities. Conclusions: In IBD, TNF alpha is strongly expressed also in plasma cells, and it is easily evidenced by conventional IHC techniques. It remains to be established whether this observation might be useful in future to establish in routine biopsy samples whether patients may be responsive to treatments toward this cytokine.

摘要： Inflammatory Bowel Diseases (IBD) are chronic inflammatory conditions of the intestinal tract. IBD are believed to result from an inappropriate immune response against the intestinal flora in genetically predisposed patients. The precise etiology of these diseases is not fully understood, therefore treatments rely on the dampening of symptoms, essentially inflammation, rather than on the cure of the disease. Despite the availability of biologics, such as anti-TNF antibodies, some patients remain in therapeutic failure and new treatments are thus needed. The multiligand receptor for advanced glycation end-products (RAGE) is a pattern recognition receptor implicated in inflammatory reactions and immune system activation. Here, we investigated the role of RAGE in intestinal inflammation and its potential as a therapeutic target in IBD. We showed that RAGE was upregulated in inflamed tissues from IBD patients compared to controls. Rage(-/-) mice were less susceptible to intestinal and colonic inflammation development than WT mice. WT mice treated with the RAGE-specific inhibitor FPS-ZM1 experienced less severe enteritis and colitis. We demonstrated that RAGE could induce intestinal inflammation by promoting oxidative stress and endothelial activation which were diminished by FPS-ZM1 treatment. Our results revealed the RAGE signaling pathway as a promising therapeutic target for IBD patients.

关键词： Anti-drug antibodies   Anti-TNF   Biologics   Drug monitoring  

摘要： Golimumab is the third anti-TNF agent approved for the treatment of ulcerative colitis. Despite initial success demonstrated by PURSUIT trials, only few real-life studies have been published evaluating its efficacy and safety in clinical practice. Its subcutaneous route and monthly administration represent an advantage in patient compliance, respectively, vs infliximab (intravenous) and adalimumab (two doses per month). The most important weakness of the molecule which often leads clinicians to choose another anti-TNF is the impossibility to dose escalate or reduce the frequency of administrations in case of secondary failure;ongoing studies are trying to solve this problem by monitoring drug levels and the eventual presence of neutralizing anti-drug antibodies. No advantage has still been demonstrated for combination therapy of golimumab with immunosuppressants and further studies are necessary to evaluate this aspect. Preliminary data also report golimumab efficacy in Crohn's disease with higher doses than in ulcerative colitis with an acceptable safety profile. Additional studies are needed in this field to confirm the initial findings.

关键词： calprotectin   Crohn's disease   diagnostic delay   early diagnosis   feasibility   general practitioner   inflammatory bowel disease   primary care   ulcerative colitis  

摘要： Aims Diagnosis of inflammatory bowel disease (IBD) is often associated with a diagnostic delay. Although faecal calprotectin is a helpful screening tool, the widespread use in primary care (PC) may not be appropriate due to the low prevalence of IBD in this setting. To increase pretest probability for a positive calprotectin test, an 8-item questionnaire (CalproQuest) was tested for its feasibility and acceptability in PC. Methods Population: PC patients with unspecific gastrointestinal complaints for at least 2 weeks. The CalproQuest consists of four major and four minor questions specific for IBD. It is considered positive if greater than or equal to two major or one major and two minor criteria are positive. Primary outcome: feasibility of CalproQuest, secondary outcome: patient's acceptance of stool sampling. Results Of 95 patients with a complete CalproQuest 52 (54.7%) were positive, 39 (41.1%) fulfilled two major and 13 (13.7%) one major and greater than or equal to two minor criteria. Twenty-seven general practitioners completed 83 (87.4%) questionnaires on feasibility which was assessed positive. Eighty-two patients (86.3%) completed questionnaires on acceptance which was high. Conclusion The CalproQuest is a feasible instrument for assessing IBD in PC. Further prospective studies concerning validity and cost effectiveness of a combined use with the calprotectin test in this setting are necessary.

关键词： BAD   bile acid diarrhea   CD   Crohn’s disease   CI   confidence interval   CRP   C-reactive protein   FC   fecal calprotectin   FGID   functional gastrointestinal disorder   FODMAP   fermentable oligosaccharides, disaccharides, monosaccharides, and polyols   GI   gastrointestinal   IBD   inflammatory bowel disease   IBS   irritable bowel syndrome   QOL   quality of life   SIBO   small intestinal bacterial overgrowth   UC   ulcerative colitis  

摘要： Description: The purpose of this clinical practice update review is to describe key principles in the diagnosis and management of functional gastrointestinal (GI) symptoms in patients with inflammatory bowel disease (IBD). Methods: The evidence and best practices summarized in this manuscript are based on relevant scientific publications, systematic reviews, and expert opinion where applicable. Best practice advice 1: A stepwise approach to rule-out ongoing inflammatory activity should be followed in IBD patients with persistent GI symptoms (measurement of fecal calprotectin, endoscopy with biopsy, cross-sectional imaging). Best practice advice 2: In those patients with indeterminate fecal calprotectin levels and mild symptoms, clinicians may consider serial calprotectin monitoring to facilitate anticipatory management. Best practice advice 3: Anatomic abnormalities or structural complications should be considered in patients with obstructive symptoms including abdominal distention, pain, nausea and vomiting, obstipation or constipation. Best practice advice 4: Alternative pathophysiologic mechanisms should be considered and evaluated (small intestinal bacterial overgrowth, bile acid diarrhea, carbohydrate intolerance, chronic pancreatitis) based on predominant symptom patterns. Best practice advice 5: A low FODMAP diet may be offered for management of functional GI symptoms in IBD with careful attention to nutritional adequacy. Best practice advice 6: Psychological therapies (cognitive behavioural therapy, hypnotherapy, mindfulness therapy) should be considered in IBD patients with functional symptoms. Best practice advice 7: Osmotic and stimulant laxative should be offered to IBD patients with chronic constipation. Best practice advice 8: Hypomotility agents or bile-acid sequestrants may be used for chronic diarrhea in quiescent IBD. Best practice advice 9: Antispasmodics, neuropathic-directed agents, and anti-depressants should be used for functional pain in IBD

关键词： INFLAMMATORY bowel diseases   ENDOSCOPY   LOGISTIC regression analysis  

摘要： Background Characterization of colonic lesions in inflammatory bowel disease (IBD) remains challenging. We developed an endoscopic classification of visual characteristics to identify colitis-associated neoplasia using multimodal advanced endoscopic imaging (Frankfurt Advanced Chromoendoscopic IBD LEsions [FACILE] classification). Methods The study was conducted in three phases: 1) development-an expert panel defined endoscopic signs and predictors of dysplasia in IBD and, using multivariable logistic regression created the FACILE classification;2) validation-using 60 IBD lesions from an image library, two assessments of diagnostic accuracy for neoplasia were performed and interobserver agreement between experts using FACILE was determined;3) reproducibility-the reproducibility of the FACILE classification was tested in gastroenterologists, trainees, and junior doctors after completion of a training module. Results The experts initially selected criteria such as morphology, color, surface, vessel architecture, signs of inflammation, and lesion border. Multivariable logistic regression confirmed that nonpolypoid lesion, irregular vessel architecture, irregular surface pattern, and signs of inflammation within the lesion were predictors of dysplasia. Area under the curve of this logistic model using a bootstrapped estimate was 0.76 (0.73-0.78). The training module resulted in improved accuracy and kappa agreement in all nonexperts, though in trainees and junior doctors the kappa agreement was still moderate and poor, respectively. Conclusion We developed, validated, and demonstrated reproducibility of a new endoscopic classification (FACILE) for the diagnosis of dysplasia in IBD using all imaging modalities. Flat shape, irregular surface and vascular patterns, and signs of inflammation predicted dysplasia. The diagnostic performance of all nonexpert participants improved after a training module.