摘要： The inflammatory changes in the placenta that are intially associated with uterine quiescence but are later associated with labor and delivery need to be elucidated. During steady state, monocytes differentiate into macrophages that maintain tolerance and homeostasis. In inflammatory states, such as inflammatory bowel disease (IBD), this differentiation is arrested, the monocyte population increases and neutrophils accumulate. Additionally, these monocytes can differentiate into dendritic cells (DCs) capable of migrating into lymph nodes where thay can prime T cells and induce an immune response. We analyzed these alterations in placentas throughout normal pregnancy as compared to those observed in a mouse model of IBD.

关键词： Inflammatory bowel disease   Crohn's disease   Ulcerative colitis   Colorectal cancer   Screening   Colonoscopy   Chemoprophylaxis  

摘要： Inflammatory bowel disease (IBD)-related colorectal cancer (CRC) is responsible for approximately 2% of the annual mortality from CRC overall, but 10-15% of the annual deaths in IBD patients. IBD-related CRC patients are also affected at a younger age than sporadic CRC patients, and have a 5-year survival rate of 50%. Despite optimal medical treatment, the chronic inflammatory state inherent in IBD increases the risk for high-grade dysplasia and CRC, with additional input from genetic and environmental risk factors and the microbiome. Recognizing risk factors, implementing appropriate surveillance, and identifying high-risk patients are key to managing the CRC risk in IBD patients. Chemoprevention strategies exist, and studies evaluating their efficacy are underway. Once dysplasia or invasive cancer is diagnosed, appropriate surgical resection and postoperative treatment and surveillance are necessary. Here, we discuss the current state of IBD-related CRC, prevalence, risk factors, and evidence for surveillance, prophylaxis, and treatment recommendations.

关键词： genetics   inborn errors of immunity   inflammatory bowel disease   pathomechanisms  

摘要： Rare, monogenetic diseases present unique models to dissect gene functions and biological pathways, concomitantly enhancing our understanding of the etiology of complex (and often more common) traits. Although inflammatory bowel disease (IBD) is a generally prototypic complex disease, it can also manifest in an early-onset, monogenic fashion, often following Mendelian modes of inheritance. Recent advances in genomic technologies have spurred the identification of genetic defects underlying rare, very early-onset IBD (VEO-IBD) as a disease subgroup driven by strong genetic influence, pinpointing key players in the delicate homeostasis of the immune system in the gut and illustrating the intimate relationships between bowel inflammation, systemic immune dysregulation, and primary immunodeficiency with increased susceptibility to infections. As for other human diseases, it is likely that adult-onset diseases may represent complex diseases integrating the effects of host genetic susceptibility and environmental triggers. Comparison of adult-onset IBD and VEO-IBD thus provides beautiful models to investigate the relationship between monogenic and multifactorial/polygenic diseases. This review discusses the present and novel findings regarding monogenic IBD as well as key questions and future directions of IBD research.

摘要： BACKGROUND: Malignancy may occur as long-term complication of inflammatory bowel disease (IBD) due to different risk factors. We assessed prevalence and incidence of malignancy, and predictive factors in the Swiss IBD Cohort Study (SIBDCS). METHODS: All IBD patients in the SIBDCS were analyzed from a cross-sectional and longitudinal perspective. Patients with malignancies were compared to controls. Standardized incidence ratios (SIR) were calculated based on age-specific and sex-specific background rates. RESULTS: Malignancies were identified in 122 of 3119 patients (3.9%). In a logistic regression model, age (OR 1.04 per year), intestinal surgery (OR 3.34), and treatment with steroids (OR 2.10) were the main predictors for the presence of malignancy, while treatment with 5-ASA (OR 0.57) and biologics (OR 0.38) were protective. From a longitudinal perspective, 67 out of 2580 patients (2.6%) were newly diagnosed with malignancy during a follow-up of 12,420.8 years (median 4.9 years). While there was no increased risk for malignancy overall (SIR 0.93, 95% CI 0.72-1.18) and colorectal cancer (SIR 1.55, 95% CI 0.71-2.95), IBD patients had an increased risk for lymphoma (SIR 2.98, 95% CI 1.36-5.66) and biliary cancer (SIR 6.3, 95% CI 1.27-18.41). In a Cox regression model, age and recent use of immunomodulators were the main predictors for development of malignancies, while 5-ASA, biologics were protective. CONCLUSIONS: IBD patients showed increased risk for lymphoma and biliary cancer, but not colorectal cancer and cancer overall. Age and recent use of immunomodulators were the main risk factors for malignancy, while aminosalicylates and biologics appear to be protective.

关键词： Crohn Disease   Inflammatory Bowel Diseases   Incidence   Colitis of Indeterminate Type   Opioids   Chronic Obstructive Airway Disease   Heart Rate  

摘要： Background Opioids are commonly prescribed to manage pain associated with inflammatory bowel disease (IBD). It is unknown what percentage of patients develop new persistent opioid use following a steroid-treated IBD flare. Aim To identify the incidence and the predictors of new persistent opioid use following an IBD flare. Methods We used a national insurance claim dataset to identify patients with IBD who received an opioid medication around the time of a corticosteroid-treated IBD flare. Patients were stratified as previously opioid naive, intermittent users, or chronic users. The incidence of persistent opioid use among the opioid-naive cohort was evaluated along with associated predictors. Results We identified 15 119 IBD patients who received opioids around the time of a flare. 5411 (35.8%) were opioid-naive patients of which 35.0% developed persistent opioid use after the flare. Factors associated with new persistent opioid use include a history of depression (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.13-1.47), substance abuse (HR 1.36, 95% CI 1.2-1.54), chronic obstructive pulmonary disease (COPD) (HR 1.17, 95% CI 1.04-1.3), as well as, Crohn's disease (HR 1.26, 95% CI 1.14-1.4) or indeterminate colitis (HR 1.6, 95% CI 1.36-1.88). Conclusions New persistent opioid use is common in IBD patients who experience a flare, especially among those with mental health disorders, COPD, and Crohn's disease or indeterminate colitis. These findings can be helpful in risk-stratifying patients when choosing an acute pain therapy and providing counselling before choosing to prescribe opioids to opioid-naive patients experiencing an IBD flare.

关键词： Crohn's disease   disability, self-report   inflammatory bowel disease   ulcerative colitis  

摘要： Background and Aim The Inflammatory Bowel Disease Disability Index (IBD-DI) is a measure of disability in inflammatory bowel disease (IBD). The IBD-DI is validated for use as a clinical interview but not for use as a self-report questionnaire. We aimed to validate the IBD-DI for self-report (IBD-DI-SR) and to reduce the number of items, using IBD patients from two centers. Methods Between April and August 2017, ambulatory IBD patients were recruited from Christchurch Hospital, New Zealand and Concord Hospital, Australia. The IBD-DI clinical interview version was compared with a self-report version. Participants were randomized to do the clinical interview or self-report first. Validation of the IBD-DI-SR involved calculating the correlation coefficient between the clinician completed and self-reported version of the IBD-DI and Cronbach's alpha of internal consistency of the IBD-DI-SR. To create an item-reduced version, multiple linear regression was used. The R-2 of the model described the overall association between the item-reduced IBD-DI-SR and the IBD-DI. Results One hundred fourteen patients (57 from Christchurch and 57 from Sydney) completed the IBD-DI-SR validation phase, of whom 63 had Crohn's disease and 51 had ulcerative colitis. The Pearson correlation coefficient between the IBD-DI-SR and IBD-DI is 0.90 (P < 0.001), and Cronbach's alpha of the IBD-DI-SR was 0.86. The item-reduced version of the IBD-DI-SR consisted of eight questions instead of 28, explaining 77% of the variance. Conclusions The IBD-DI-SR has demonstrated reliability and validity. The item-reduced IBD-DI-SR is a concise self-report instrument for measuring IBD disability, which makes the IBD-DI more widely usable.

关键词： faecal calprotectin   inflammatory bowel disease   cost utility   colonoscopy  

摘要： BackgroundFaecal calprotectin (FC) is an accurate biomarker of disease activity in inflammatory bowel disease (IBD), yet the cost/resource implications of incorporating FC into real-world' practice remain uncertain. AimTo evaluate the utility of FC in clinical decision-making and on healthcare costs in IBD. MethodsRetrospective data, including colonoscopy/other investigations, medication, admission and surgical data, were collected from hospital records and compared between two groups: pre-FC historical cohort (2005-2009) where colonoscopy was used to assess IBD activity versus the cohort where FC was used first instead (2010-2014). Post-test costs were also compared. ResultsA total of 357 FC tests (246 patients, 2010-2014) and 450 colonoscopies (268 patients, 2005-2009) were performed. On subsequent review, both FC and colonoscopy (in their respective cohorts) were associated with changes in management in 50.7 versus 56.2% (P = 0.14), respectively, with similar proportions of subsequent IBD-related investigations within 6 months (21.8 vs 21.9%, P = 1.0). Prior to FC availability (2005-2009), a colonoscopy for disease reassessment cost AU$606 578 (cost per patient-year $1887.34) versus AU$282 048 (cost per patient-year $968.60) when FC colonoscopy was used (2010-2014). Within the FC cohort, 73.6% did not proceed to colonoscopy within 6 months post-FC, and 60.6% had not undergone colonoscopy post-FC by the end of follow up (median 1.8 years (0.1, 4.6) post-FC). Those with FC 250 were scoped earlier than those with FC < 100 g/mL (median 0.49 vs 1.0 years, P = 0.03). ConclusionIntroduction of FC into routine IBD care aided changes in clinical management in a similar proportion, yet at potentially half the total cost, compared to a historical colonoscopy-only cohort at the same centre.

关键词： Crohn's disease   inflammatory bowel disease   ulcerative colitis   vitamin D   vitamin D receptor  

摘要： Background: The intestinal vitamin D receptor (VDR) remains poorly characterized in patients with inflammatory bowel disease (IBD). Methods: Colonoscopic biopsies and intestinal resection specimens from the terminal ileum, ascending and sigmoid colon, from patients with and without IBD, were analyzed for VDR mRNA quantification by polymerase chain reaction, and protein localization and semi-quantification by immunohistochemistry. The relationship between VDR and intestinal inflammation, serum 25(OH)D and oral vitamin D intake was elicited. Results: A total of 725 biopsies from 20 patients with Crohn's disease (CD), 15 with ulcerative colitis (UC) and 14 non-IBD controls who underwent colonoscopy were studied. VDR gene expression and protein staining intensity was similar across all three groups, and across the intestinal segments. Sigmoid colon VDR mRNA expression inversely correlated with faecal calprotectin (r = -0.64, p = 0.026) and histological score (r = -0.67, p = 0.006) in UC, and histological score (r = -0.58, p = 0.019) in patients with CD. VDR staining intensity was higher in quiescent than diseased segments. No relationship with serum 25(OH)D or oral vitamin D intake was noted. Immunohistochemical staining of 28 intestinal resection specimens from 15 patients (5 each with CD, UC and non-IBD controls) showed diffuse VDR staining in the mucosa, submucosa and circular muscle. Conclusions: VDR transcript expression and protein staining intensity are inversely related to inflammation in IBD, but unrelated to serum 25(OH)D, and similar to non-IBD controls. Strategies to upregulate intestinal VDR, potentially translating to modulation of disease activity, require investigation.

摘要： Disease heterogeneity hampers achieving long-term disease remission in inflammatory bowel disease (IBD). Monitoring ongoing tissue-localized regulatory and inflammatory T-cell responses in peripheral blood would empower disease classification. We determined whether regulatory and inflammatory phenotypes of circulating CD38(+) effector (CD62L(neg)CD4(+)) T cells, a population enriched for cells with mucosal antigen specificity, classify disease course in pediatric IBD patients. In healthy individuals, circulating CD38(+) effector T cells had a predominant regulatory component with lower frequencies of IFN gamma-secreting T cells, higher frequencies of IL-10-secreting T cells and higher frequencies of inhibitory molecule T-cell immunoglobulin and ITIM domain(+) (TIGIT) cells than CD38(neg) effector T cells. TIGIT expression was stable upon stimulation and marked CD38(+) T cells with inhibitory properties. In IBD patients with active intestinal inflammation this predominant regulatory component was lost: circulating CD38(+) effector T cells had increased activated CD25(+) CD45RA(neg) and decreased TIGIT(+) cell frequencies. TIGIT percentages below 25% before treatment associated with shorter duration of clinical remission. In conclusion, phenotypic changes in circulating CD38(+) effector T cells, in particular the frequency of TIGIT(+) cells, classify pediatric IBD patients and predict severity of disease course. These findings have relevance for IBD and can be exploited in graft-versus-host-disease and checkpoint inhibitor-induced inflammation in cancer.

关键词： Co-occurrence   LRRK2   Population-based   Risk ratio  

摘要： Background: Several studies have reported an increased prevalence of Parkinson disease (PD) amongst patients with inflammatory bowel disease (IBD) with conflicting results. We aimed to evaluate the risk of PD in the IBD population by conducting a meta-analysis (MA). Methods: A systematic review with MA of the existing literature was conducted. The main outcome of interest was the incidence of developing PD in patients previously diagnosed with IBD. Results: Four studies were included in this MA. The overall risk of PD in IBD was significantly higher than controls (RR 1.41, 95% c.i. 1.19-1.66). Crohn's disease had a 28% increased risk of PD and ulcerative colitis had a 30% increased risk of PD compared to controls (CD: RR 1.28, 95% c.i. 1.08-1.52, UC: RR 1.30, 95% c.i. 1.15-1.47). Conclusion: The MA detected an increased risk of PD in the IBD population and CD/UC subgroup. These results merit further clinical validation in future studies. (C) 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.