关键词： Crohn Disease   reactivation tuberculosis   Biologic Products   Inflammatory Bowel Diseases   infection risk   Intestinal Diseases   Biological Therapy   Patients  

摘要： The development of biologic drugs revolutionized the management of inflammatory bowel diseases: Crohn's disease and ulcerative colitis. However, while their efficacy has been well established, it remains uncertain to what extent biologic treatments may be associated with important safety risks, such as serious infections, opportunistic infections, or tuberculosis reactivation. Herein, we review and discuss the current evidence on the infection risk associated with biologic therapy in patients with inflammatory bowel disease (IBD).

关键词： Stenosis   Colitis   Mesenchymal Cells   Epithelial-to-Mesenchymal Transition  

摘要： BACKGROUND: Intestinal fibrosis resulting in (sub) obstruction is a common complication of Crohn's disease (CD). Rho kinases (ROCKs) play multiple roles in TGFb-induced myofibroblast activation that could be therapeutic targets. Because systemic ROCK inhibition causes cardiovascular side effects, we evaluated the effects of a locally acting ROCK inhibitor (AMA0825) on intestinal fibrosis. METHODS: Fibrosis was assessed in mouse models using dextran sulfate sodium (DSS) and adoptive T-cell transfer. The in vitro and ex vivo effects of AMA0825 were studied in different cell types and in CD biopsy cultures. RESULTS: ROCK is expressed in fibroblastic, epithelial, endothelial, and muscle cells of the human intestinal tract and is activated in inflamed and fibrotic tissue. Prophylactic treatment with AMA0825 inhibited myofibroblast accumulation, expression of pro-fibrotic factors, and accumulation of fibrotic tissue without affecting clinical disease activity and histologic inflammation in 2 models of fibrosis. ROCK inhibition reversed established fibrosis in a chronic DSS model and impeded ex vivo pro-fibrotic protein secretion from stenotic CD biopsies. AMA0825 reduced TGFb1-induced activation of myocardin-related transcription factor (MRTF) and p38 mitogen-activated protein kinase (MAPK), down-regulating matrix metalloproteinases, collagen, and IL6 secretion from fibroblasts. In these cells, ROCK inhibition potentiated autophagy, which was required for the observed reduction in collagen and IL6 production. AMA0825 did not affect pro-inflammatory cytokine secretion from other ROCK-positive cell types, corroborating the selective in vivo effect on fibrosis. CONCLUSIONS: Local ROCK inhibition prevents and reverses intestinal fibrosis by diminishing MRTF and p38 MAPK activation and increasing autophagy in fibroblasts. Overall, our results show that local ROCK inhibition is promising for counteracting fibrosis as an add-on therapy for CD.

关键词： children   colectomy   primary sclerosing cholangitis   ulcerative colitis  

摘要： Objectives: In adults, primary sclerosing cholangitis (PSC), a cholestatic liver disease characterized by inflammation/fibrosis of intra/extrahepatic bile ducts, associates with a milder form of inflammatory bowel disease (IBD), particularly ulcerative colitis (UC). The pediatric PSC-IBD phenotype is less well characterized. Methods: We performed a retrospective, single-center study examining patients with PSC-IBD at Texas Children's Hospital between 2000 and 2015. IBD-phenotype (Modified Montreal Classification), medications, laboratory values, endoscopic records, and IBD-based hospital admissions were collected. PSC-UC phenotype was compared to UC, non-PSC patients (n = 95) from Texas Children's Hospital. Elevated gamma-glutamyl transpeptidase levels were compared to calprotectin levels and IBD-flare activity, that is, gastrointestinal symptoms resulting in office/emergency department visits or hospital admission. Results: Of 39 patients with PSC-IBD, 34 (87.2%) had UC (PSC-UC) and 5 (12.8%) had Crohn disease. Pancolitis was more common in PSC-UC than UC, non-PSC (96.3%, 64%, P = 0.0009). Patients with PSC-UC required less treatment with steroids (76.5%, 91.6%, P = 0.0326) or infliximab (8.8%, 37.9%, P = 0.0011), and fewer had at least 1 IBD-related hospital admission (32.4%, 63.2%, P = 0.0025) than UC, non-PSC. Progression to colectomy was significantly less (5.8%, 24.2%, P = 0.0223) in PSC-UC. Median diagnosis-to-colectomy time tended to be longer in PSC-UC (6.37, 2.5 years, P = 0.0792). In 2 smaller subsets, gamma-glutamyl transpeptidase did not correlate with calprotectin in PSC-UC (n = 11, P = 0.7922) and less strongly associated with IBD-flares in PSC-UC than UC, non-PSC (n = 33, n = 67;15.2%, 41.8%, P = 0.0120). Conclusions: Pediatric PSC appears to associate with milder pancolitic-UC. PSC and IBD activity do not appear to correlate. Our findings may provide useful information toward etiology and management of pediatric PSC-IBD.

关键词： Inflammatory bowel disease   Blood pressure   Blood pressure monitoring   Ulcerative colitis   Masked hypertension  

摘要： Masked hypertension (MHTN) and lack of nocturnal dipping in blood pressure (BP) have been linked to the state of inflammation. We aimed to assess the frequency of nocturnal patterns of BP and heart rate (HR) in patients with IBD. Sixty-three normotensive patients with confirmed IBD during remission and 63 healthy subjects were enrolled in a case-control study. All subjects were monitored for BP and HR over a period of 24 h under ambulatory setting. Means for BP and HR were calculated for nighttime and daytime periods. Daytime BP ae 135/85 mmHg, nighttime BP ae 120/70 mmHg, and 24-h average BP ae 130/80 mmHg were defined as MHTN. The main end points of this study were lack of > 10% nocturnal decrease in the systolic BP (NDP-BP) and in HR (NDP-HR). After exclusion of 8 patients with IBD from analysis, 55 patients and 63 control subjects (49% men) with a mean age of 37.5 +/- 11.0 years were enrolled. NDP-BP was more common in the IBD group compared to controls (55 vs. 33%;P = 0.026). MHTN was detected in 24% of IBD patients compared to 8% among controls (P = 0.017). Meanwhile, NDP-HR was observed in 22% of the IBD patients and 30% of the control group (P = 0.402). IBD remained a significant predictor of NDP-BP (odds ratio 2.60, 95% confidence interval 1.19-5.51) following an adjustment for age and gender. IBD is associated with higher frequency of NDP-BP and MHTN;however, nocturnal changes in HR were similar in both groups.

关键词： Crohn's disease   infliximab   observance   predictor   ulcerative colitis  

摘要： OBJECTIVE: To assess adherence to infliximab (IFX) therapy in inflammatory bowel disease patients, to investigate reasons for non-adherence and to identify predictors for non-adherence. METHODS: This observational study was conducted in two French referral university hospitals between 1 September and 31 October, 2011. Patients were systematically asked if they had already delayed or missed an IFX perfusion since the beginning of the treatment and about the reasons for their nonadherence. RESULTS: Of the 162 included patients (121 Crohn's disease [CD], 41 ulcerative colitis), 87 (53.7%) reported a delay of at least one IFX injection and 14 (8.6%) missed at least one IFX perfusion since the beginning of the treatment. The overall non-adherence rate was 54.3%. Pooling all misses, the main reasons for non-adherence were pregnancy (33.3%), intentional non-adherence (20%) and forgetfulness (13.3%). Pooling all delays, the main reasons for nonadherence were professional constraints (46.9%), infections (17.3%) and travels (14.3%). Perineal disease was associated with IFX delays (P = 0.0007, odds ratio 4.0), whereas active CD/UC was associated with IFX misses (P = 0.0258, OR = 5.4). CONCLUSIONS: The overall non-adherence rate for IFX use was 54.3%. Professional constraints and intentional non-adherence were the leading causes of non-adherence. Perineal disease and active CD were negatively related to adherence.

关键词： faecal calprotectin   immunoassays   inflammatory bowel disease  

摘要： Background: We evaluated the analytical performance of six different faecal calprotectin immunoassays together with their diagnostic accuracy in the discrimination between functional and organic bowel disorders. Methods: The faecal samples were obtained from inflammatory bowel disease patients (n = 27) at the time of diagnosis [Crohn's disease (n = 15), colitis ulcerosa (n = 12)], gastroenterologic disease control patients (n = 52) and rheumatologic disease control patients (n = 26). All individuals included in the study underwent a concurrent ileocolonoscopy. Analytical performance (imprecision, accuracy, carry-over, correlation and agreement) and diagnostic accuracy (sensitivity, specificity, likelihood ratios) of the different assays were evaluated. Results: All methods demonstrated good analytical performance, but within-run and total imprecision varied depending on the assay methodology used. Using Passing Bablok and Bland-Altman analyses, low quantitative agreement was observed between the assays. All assays showed excellent diagnostic accuracy, with areas under the receiver operating characteristic curves (ROC) ranging from 0.974 to 0.998. The AUCs were not significantly different between assays (p > 0.05). Diagnostic sensitivity at the cut-off at a fixed specificity of 75% ranged from 95.2% to 100%. Introduction of multiple result intervals increased the clinical interpretation of all the assays. Conclusions: Analytical and diagnostic performance of the evaluated faecal calprotectin assays is good, but numerical values differ substantially between the assays necessitating the use of different clinical cut-offs. Introduction of multiple result intervals aids in clinical decision-making.

关键词： Inflammatory bowel disease   Bone strength   Muscle functions   Peripheral quantitative computed tomography   Mechanography   Vitamin D  

摘要： Low bone mineral density (BMD) and an increased fracture incidence are two extraintestinal complications associated with inflammatory bowel disease (IBD). We aimed to evaluate musculoskeletal traits and assess vertebral fracture (VF) rate in children and adolescents with IBD. Seventy patients with IBD with a median age of 13.8 years were included. The BMD and geometric parameters of the non-dominant tibia were assessed using pQCT. Dynamic muscle functions were evaluated using jumping mechanography. VFs were assessed according to the semiquantitative standardized method by Genant. The muscle functions adjusted for the patients' weight did not differ from the reference population. A low trabecular BMD (Z-score - 1.6;p < 0.001) and cortical thickness (Z-score - 0.7;p < 0.001) were found in children and adolescents with IBD. Conversely, an increased cortical BMD (Z-score 1.1;p < 0.001) was noted. No significant association was found between the 25-OHD serum levels and the bone or muscle measurements. One patient with asymptomatic VF was identified. Conclusion: IBD in childhood or adolescents affects bones but not muscles. Bone changes are independent of the 25-OHD serum level. A thoracolumbar spine X-ray should not be routinely recommended in children with IBD.