关键词： inflammatory bowel disease unclassified   prognosis   treatment  

摘要： Background and Aim A definitive diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) is not always possible, and a proportion of patients will be diagnosed as inflammatory bowel disease unclassified (IBDU). The aim of the study was to investigate the prognosis of patients initially diagnosed with IBDU and the disease course during the following 5 years. Methods The Epi-IBD study is a prospective population-based cohort of 1289 IBD patients diagnosed in centers across Europe. Clinical data were captured prospectively throughout the follow-up period. Results Overall, 476 (37%) patients were initially diagnosed with CD, 701 (54%) with UC, and 112 (9%) with IBDU. During follow-up, 28 (25%) IBDU patients were changed diagnoses to either UC (n = 20, 71%) or CD (n = 8, 29%) after a median of 6 months (interquartile range: 4-12), while 84 (7% of the total cohort) remained IBDU. A total of 17 (15%) IBDU patients were hospitalized for their IBD during follow-up, while 8 (7%) patients underwent surgery. Most surgeries (n = 6, 75%) were performed on patients whose diagnosis was later changed to UC;three of these colectomies led to a definitive diagnosis of UC. Most patients (n = 107, 96%) received 5-aminosalicylic acid, while 11 (10%) patients received biologicals, of whom five remained classified as IBDU. Conclusions In a population-based inception cohort, 7% of IBD patients were not given a definitive diagnosis of IBD after 5 years of follow-up. One in four patients with IBDU eventually was classified as CD or UC. Overall, the disease course and medication burden in IBDU patients were mild.

关键词： Crohn's diseaseMicrobiomeSystems analysisUlcerative colitis  

摘要： Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, affect several million individuals worldwide. Crohn's disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 time points each;in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation. The study's infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi'omics Database (http://***), provide the most comprehensive description to date of host and microbial activities in inflammatory bowel diseases.

关键词： Bacterial beta-glucuronidase   Colitis   Inflammatory bowel disease   Digestive proteases  

摘要： Objective: Inflammatory bowel diseases (IBD) including ulcerative colitis and Crohn's disease are devastating diseases of the gut. At present, all the treatments are mainly targeting symptoms like inflammation. The disease remains regarded as incurable, largely due to lacking of knowledge on its etiology. Our previous studies suggested that impaired inactivation of digestive proteases by deconjugated bilirubin in experimental colitis, thus bacterial beta-glucuronidase for catalyzing the reaction, may have played critical role in the pathogenesis of IBD. Methods: We first analyzed beta-glucuronidase activity in gut tissue and feces of mice by a colitis model. Then the effect of beta-glucuronidase on experimental colitis was investigated in detail by administration of beta-glucuronidase (from E. coli) and fecal material transplantation to mice with 3% DSS in drinking water for 7 days. Results: Mice with colitis showed unchanged activity of beta-glucuronidase in colon tissue but decreased activity in feces. Treatment with bacterial beta-glucuronidase at 100 U or above alleviated DSS-induced colitis as demonstrated by the less body weight loss, less disease activity score, increased expression of tight junction proteins and decreased gut permeability, decreases in MPO, TNF-alpha, IL-10, TLR-4 and MyD88, and increase in IL-10 and I kappa B3 alpha in gut, restored fecal beta-glucuronidase and gut microbiota along with decreases in fecal digestive proteases. Transplantation of fecal material from control to colitis mice showed similar effects as treatment with beta-glucuronidase. Conclusions: Bacterial beta-glucuronidase showed strong inhibition on colitis along with the reduction in fecal digestive proteases, which may be a crucial diagnostic and therapeutic target for IBD. (C) 2019 Published by Elsevier Inc.

关键词： Biopsy   Case series   Clinical medicine   Clinical research design   Clinical trials   Database and informatics methods   Database searching   Drug research and development   Gastroenterology and hepatology   Inflammatory bowel disease   Medicine and health sciences   Observational studies   Pharmacology   Randomized controlled trials   Research and analysis methods   Research Article   Research assessment   Research design   Routes of administration   Surgical and invasive medical procedures   Systematic reviews  

摘要： Background The recently established association between higher levels of DNA-incorporated thioguanine nucleotides and lower relapse risk in childhood acute lymphoblastic leukaemia (ALL) calls for reassessment of prolonged 6-thioguanine (6TG) treatment, while avoiding the risk of hepatotoxicity. Objectives To assess the incidence of hepatotoxicity in patients treated with 6TG, and to explore if a safe dose of continuous 6TG can be established. Data sources Databases, conference proceedings, and reference lists of included studies were systematically searched for 6TG and synonyms from 1998-2018. Methods We included studies of patients with ALL or inflammatory bowel disorder (IBD) treated with 6TG, excluding studies with 6TG as part of an intensive chemotherapy regimen. We uploaded a protocol to PROSPERO (registration number CRD42018089424). Database and manual searches yielded 1823 unique records. Of these, 395 full-texts were screened for eligibility. Finally, 134 reports representing 42 studies were included. Results and conclusions We included data from 42 studies of ALL and IBD patients;four randomised controlled trials (RCTs) including 3,993 patients, 20 observational studies including 796 patients, and 18 case reports including 60 patients. Hepatotoxicity in the form of sinusoidal obstruction syndrome (SOS) occurred in 9-25% of the ALL patients in two of the four included RCTs using 6TG doses of 40-60 mg/m(2)/day, and long-term hepatotoxicity in the form of nodular regenerative hyperplasia (NRH) was reported in 2.5%. In IBD patients treated with 6TG doses of approximately 23 mg/m(2)/day, NRH occurred in 14% of patients. At a 6TG dose of approximately 12 mg/m(2)/day, NRH was reported in 6% of IBD patients, which is similar to the background incidence. According to this review, doses at or below 12 mg/m(2)/day are rarely associated with notable hepatotoxicity and can probably be considered safe.

关键词： Vitamin D deficiency   Vitamin D   Medical risk factors   Regression analysis   Ulcerative colitis   Seasons   Crohn's disease   Inflammatory bowel disease  

摘要： Objectives Vitamin D deficiency predicts unfavorable disease outcomes in inflammatory bowel disease. Endogenous vitamin D synthesis is affected by seasonal factors including sunlight exposure, raising the question whether seasonality determines the risk of vitamin D deficiency and may mask other clinical risk factors. Methods Univariable and multiple regression analyses were performed in a retrospective cohort of 384 patients to determine risk factors for vitamin D deficiency. Since the observed 25-hydroxyvitamin D [25(OH) D] concentrations followed a sinusoidal pattern over the year, all 25 (OH) D concentrations were normalized for the predicted variability of the respective day of analysis based on a sinusoidal regression analysis of 25(OH) D test results obtained in more than 86,000 control serum samples. Results Vitamin D deficiency was highly prevalent in patients with Crohn's disease or ulcerative colitis (63% and 55%, respectively) and associated with winter/spring seasons. After normalization of 25(OH) D concentrations for the day of analysis, vitamin D deficiency was associated with histories of complications related to inflammatory bowel disease, surgery, smoking and ongoing diarrhea while initial disease manifestation during adulthood, ongoing vitamin D supplementation and diagnosis of ulcerative colitis vs. Crohn's disease appeared to be protective. Multiple regression analyses revealed that vitamin D deficiency was associated with disease activity in Crohn's disease and anemia in ulcerative colitis patients. Only few deficient patients achieved sufficient 25(OH) D concentrations over time. However, increasing 25(OH) D concentrations correlated with improved Crohn's disease activity. Conclusions Vitamin D deficiency was highly prevalent in patients with Crohn's disease and ulcerative colitis and dependent on the season of the year. Following normalization for seasonality by sinusoidal regression analysis, vitamin D deficiency was found to be associated w

关键词： Chitosan microparticles   Mesalazine   Inflammatory bowel diseases   Anti-inflammatory effect   In vivo model  

摘要： The development of innovative strategies for the efficacious treatment of inflammatory bowel diseases (IBD) still remains a goal for pharmaceutical research. Targeting the lower section of the intestine is the main aim of therapy because it is the compartment primarily affected by IBDs. Mesalazine was microencapsulated in chitosan particles in order to modulate its unfavorable pharmacokinetic profile exploiting the bioadhesive feature of the polysaccharide and increase the anti-inflammatory effect of the drug following its rectal administration in an in vivo model of induced IBD. The chitosan microparticles (1-4 mu m mean size) allowed efficient retention of the mesalazine and a prolonged drug release lasting up to 48 h. In vitro and in vivo experiments confirmed the significant mucoadhesion feature of the formulation by means of mucin assay and CLSM experiments and demonstrated its therapeutic efficacy at a drug concentration 2-fold lower than the commercial formulation Asamax (R) (13 mg/kg vs 26 mg/kg).

关键词： Inflammatory bowel disease   ATP   P2X7 receptor  

摘要： Inflammatory bowel disease is a chronic nonspecific inflammatory disease of the intestine. Its pathogenesis is not yet fully understood. It may be related to heredity, environmental triggers, infection, immune dysfunction and other factors. Purinergic receptor (P2X7R) ligand-gated ion channel is closely related to inflammation and widely expressed in intestinal cells. Previous studies have shown that ATP/P2X7R signal is involved in the pathogenesis of intestinal inflammation, but its specific mechanism needs further study. This article reviews the research progress of P2X7 receptor in inflammatory bowel disease.

关键词： Inflammatory bowel diseases   ultrasound   fecal calprotectin   pediatric   children   diagnosis   Crohn's disease  

摘要： Objective: To assess the accuracy of noninvasive parameters, fecal calprotectin (FC), increased bowel wall thickening (BWT) at intestinal ultrasound (IUS) and blood inflammatory indexes (BII), alone or in combination, as diagnostic tools for inflammatory bowel disease (IBD) in pediatric patients. Methods: Retrospective data were collected on consecutive children (age 2-18 years) referred to our pediatric gastroenterology clinic, for recurrent abdominal pain and/or altered bowel habit from 2007 to 2013. Subjects who had diagnostic workup: laboratory tests (FC, BII, white blood cell (WBC), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)) and IUS as initial assessment were eligible. Subjects with known gastrointestinal (GI) diseases, or signs or symptoms highly suggestive for organic diseases necessitating prompt endoscopy (e.g., perianal disease or rectal bleeding), or who had recently performed endoscopy were excluded. The accuracy of noninvasive tests for detecting IBD was assessed using endoscopic and/or radiological investigations, performed in subsequent clinical follow up, as reference gold standard. Results: Seventy-seven patients (mean age 11.3, 44 males) were included, 23 (29.9%) with a final diagnosis of IBD. As single tests, FC gave the highest sensitivity (96%) but lower specificity (72%) and IUS highest specificity (96%) with lower sensitivity (70%). The combination of FC + IUS showed excellent accuracy for detecting children with IBD with positive predictive value: 100%;negative predictive value: 88.5%. The probability of IBD in children with normal FC, BII and IUS was 0.09%. Conclusions: FC and increased BWT at IUS are accurate to guide reassurance or proceeding with further invasive procedures for detecting IBD in children with mild GI symptoms.

关键词： Inflammatory bowel disease   Crohn's disease   ulcerative colitis   quality of life   Short Health Scale  

摘要： Objectives: Patient reported outcomes are widely used in today's clinical practice. The Short Health Scale has been proven to be an easy-to-use and reliable measure to evaluate quality of life in patients with inflammatory bowel disease. We aimed to validate this Short Health Scale in Dutch speaking ***: A total of 157 Crohn's disease and ulcerative colitis patients (46% male, median age 39years) completed the Short Health Scale on a tablet during the outpatient clinic. Validity was assessed by correlating both individual and total Short Health Scale scores with short Inflammatory Bowel Disease Questionnaire dimensions and clinical disease activity. Test-retest reliability was assessed in eight patients in stable remission who completed the Short Health Scale a second time after ***: All Short Health Scale items correlated with corresponding short Inflammatory Bowel Disease Questionnaire dimensions (correlation coefficients ranging from -0.403 to -0.833, all p<.01). Short Health Scale scores increased stepwise with increasing clinical disease activity (all p<.001). The results of the Short Health Scale questionnaire remained stable on repeated measurements in patients in remission (r(s) between 0.699 and 0.994, all p<.01 except for well-being).Conclusions: The Short health Scale is a rapid and valid instrument for measuring quality of life in Dutch speaking patients with Inflammatory Bowel Disease. Its simplicity and usability make it a good candidate for routine care and suitable for home-monitoring of patients.

关键词： anti-TNF   biological   inflammatory bowel disease   Crohn's disease   ulcerative colitis   paediatrics   children   adolescents  

摘要： Inflammatory bowel disease (IBD) presents with disabling symptoms and may lead to insufficient growth and late pubertal development in cases of disease onset during childhood or adolescence. During the last decade, the role of anti-tumor necrosis factor (TNF) in the treatment of paediatric-onset IBD has gained more ground. The number of biologicals presently available for children and adolescents with IBD has increased, biosimilars have become available, and practices in adult gastroenterology with regards to anti-TNF have changed. The aim of this study is to review the current evidence on the indications, judicious use, effectiveness and safety of anti-TNF agents in paediatric IBD. A PubMed literature search was performed and included articles published after 2000 using the following terms: child or paediatric, Crohn, ulcerative colitis, inflammatory bowel disease, anti-TNF, TNF alpha inhibitor, infliximab, adalimumab, golimumab and biological. Anti-TNF agents, specifically infliximab and adalimumab, have proven to be effective in moderate and severe paediatric IBD. Therapeutic drug monitoring increases therapy effectiveness and safety. Clinical predictors for anti-TNF response are currently of limited value because of the variation in outcome definitions and follow-ups. Future research should comprise large cohorts and clinical trials comparing groups according to their risk profile in order to provide personalized therapeutic strategies.