关键词： Cytokines   Gastroenterology   Inflammatory bowel disease   Vascular Biology   endothelial cells  

摘要： Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with rising incidence. Diseased tissues are heavily vascularized. Surprisingly, the pathogenic impact of the vasculature in IBD and the underlying regulatory mechanisms remain largely unknown. IFN-gamma is a major cytokine in IBD pathogenesis, but in the context of the disease, it is almost exclusively its immune-modulatory and epithelial cell-directed functions that have been considered. Recent studies by our group demonstrated that IFN-gamma also exerts potent effects on blood vessels. Based on these considerations, we analyzed the vessel-directed pathogenic functions of IFN-gamma and found that it drives IBD pathogenesis through vascular barrier disruption. Specifically, we show that inhibition of the IFN-gamma response in vessels by endothelial-specific knockout of IFN-gamma receptor 2 ameliorates experimentally induced colitis in mice. IFN-gamma acts pathogenic by causing a breakdown of the vascular barrier through disruption of the adherens junction protein VE-cadherin. Notably, intestinal vascular barrier dysfunction was also confirmed in human IBD patients, supporting the clinical relevance of our findings. Treatment with imatinib restored VE-cadherin/adherens junctions, inhibited vascular permeability, and significantly reduced colonic inflammation in experimental colitis. Our findings inaugurate the pathogenic impact of IFN-gamma-mediated intestinal vessel activation in IBD and open new avenues for vascular-directed treatment of this disease.

关键词： laparoscopy   subtotal colectomy   inflammatory bowel disease   single port  

摘要： Background: Single incision laparoscopic surgery (SILS) is expanding, enhancing the advantages of multi-port laparoscopic surgery (MLS). Limited literature exists regarding SILS total/subtotal colectomies for inflammatory bowel disease (IBD). Aim of the study was to present the initial experience with this type of approach in a district general hospital and extrapolate its feasibility and safety in this specific context based on gold standard outcomes reported in literature. Materials and Methods: Preoperative parameters, operative details and surgical outcomes of consecutive patients who underwent colonic SILS for IBD in a 5-year period were reviewed retrospectively. Median length of follow-up was 26 months. Results: Fourteen patients underwent SILS subtotal/total colectomy. Median body mass index was 25 (18.1-35). Two patients had previous abdominal surgeries. Median operating time was 202.5 minutes. Two cases were converted to open. Median length of stay was 5 days. Three patients presented complications. Three patients developed parastomal hernias (21.4%). Five out of 12 patients with ulcerative colitis declined further surgery, 3 are awaiting laparoscopic/SILS pouch formation, 1 underwent SILS pouch formation, 1 SILS ileo-rectal anastomosis and 1 patient had SILS completion proctectomy. One patient was not followed up. Conclusions: Despite literature data heterogeneity, these results provide support to the feasibility and applicability of SILS in the subgroup of patients who undergo subtotal/total colectomies for IBD, offering the option for subsequent SILS completion or restorative procedures. Further studies are required to explore the benefit of SILS over MLS (including cosmesis and quality of life) and non-inferiority of SILS regarding the parastomal hernia issue and the operative duration.

关键词： Tomography, X-ray computed   Radiation exposure   Contrast media   Image quality   Inflammatory bowel disease   Abdomen, acute  

摘要： Purpose: To prospectively evaluate image quality and diagnostic efficacy of a low radiation-high contrast (LR-HC) CT Enterography (CTE) in active Inflammatory Bowel Disease (IBD). Materials and methods: Eighty-five (36M;49F;1775 yrs) patients with active IBD underwent contrast-enhanced CTE and were stratified in two groups according to age (< or >= 45 yrs): Group A (N = 45;32 +/- 9 yrs;58 +/- 10 kg) and Group B (N = 40;58 +/- 10 yrs;61 +/- 13 kg). Each group received a different amount of radiation (Noise Index, NI) and non-ionic iodinated contrast media (LOCM) as follows: Group A (NI = 15;2.5 ml/kg) and Group B (NI = 12.5;2 ml/kg). Thyroid functional tests were performed in all patients of group A at 4-6 wks. Signal- and contrast-to-noise ratios were calculated for liver (L) and abdominal aorta (A). Statistical analysis was performed by Student's t- or Chi-square test for continuous and categorical data, respectively. Results: No patient of Group A developed signs of thyrotoxicosis. SNRL, CNRL and diagnostic accuracy of CTE were 8.4 +/- 1.7 vs 8.9 +/- 2.1 (p = 0.256), 5.4 +/- 1.5 vs 5.6 +/- 1.7 (p = 0.486) and 91.1 vs 92.5% (p = 0.764) whereas the effective dose and the LOCM administered were 6.7 +/- 2.2 vs 13.9 +/- 6.0 mSv (p < 0.001) and 144 +/- 25 vs 122 +/- 25 ml (p < 0.001) for Group A and B, respectively. Conclusion: LR-HC CTE is a dose-effective protocol in the evaluation of active IBD in young patients.

关键词： antibodies to adalimumab   antibodies to infliximab   antibody suppression   inflammatory bowel disease   tumor necrosis factor-alpha  

摘要： Background:Treatment of pediatric inflammatory bowel disease (IBD) with monoclonal anti- tumor necrosis factor-alpha (TNF alpha) can result in immunogenicity and formation of anti-drug antibodies (ADAs). ADAs are associated with loss of clinical response and worsening disease progression. Data examining treatment interventions to overcome ADA in pediatric patients with IBD are ***:Medical records were reviewed from 234 children and adolescents with IBD treated with infliximab or adalimumab who underwent therapeutic drug monitoring (626 tests). All patients who had detectable antibodies were further analyzed. A total 58 patients (24.8%) developed ADA while being treated with infliximab or adalimumab. The incidence of antibody development was 12.9 per 100 person-years of anti-TNF treatment. Twenty-eight patients underwent dose optimization and 54% had undetectable ADA on follow-up monitoring. The mean duration of antibody suppression was 16.810.9 months in those who were successfully suppressed with optimization. Patients who switched to a second anti-TNF medication were not more likely to develop antibodies to the second ***:With limited therapies for IBD and the chronicity of the disease, we advocate salvage of the current anti-TNF through dose optimization in pediatric patients with antibody level <10U/mL.

关键词： Outcome   Originator Drug   TNF Antagonist   Drug Monitoring  

摘要： BACKGROUND & AIMS: There is evidence that it is safe and effective for patients with inflammatory bowel diseases (IBD) to switch from maintenance therapy with an original infliximab drug to a biosimilar, but little is known about outcomes of reverse switches and/or multiple switches. We aimed to evaluate the effects of a reverse switch (from a biosimilar to Remicade) in a real-life cohort. METHODS: We performed a prospective observational study of 174 unselected and consecutive patients with IBD (136 with Crohn's disease [CD] and 38 with ulcerative colitis [UC]) who received maintenance therapy with the biosimilar in Hungary. In September 2017, patients were switched from the biosimilar (CT-P13) to Remicade, due to reimbursement policies. In our cohort, 8% (n = 14) patients had been previously exposed to the originator Remicade. We collected clinical and biochemical information from patients at baseline (time of the switch) and 16 and 24 weeks thereafter. Clinical remission was defined as a Crohn's disease activity index <150 points or no fistula drainage, or a partial Mayo score <3 points for patients with UC. Serum drug trough levels and anti-drug antibodies were measured at baseline and week 16. RESULTS:There was no significant difference in the proportion of patients in clinical remission at week 8 before the switch (82.5% with CD and 82.9% with UC), at baseline (80.6% with CD and 81.6% with UC), at week 16 (77.5% with CD and 83.7% with UC), or at week 24 (CD 76.3% with CD and 84.9% with UC) (P = .60 among groups for patients with CD and P = .98 among groups for patients with UC). For all patients, mean serum trough levels of infliximab were 5.33 +/- 4.70 mu g/mL at baseline and 5.69 +/- 4.94 mu g/mL at week 16 (P = .71);we did not find significant differences in prevalence of anti-drug antibody at baseline (16.2%) compared with week 16 (16.9%) (P = .87). Four infusion reactions occurred, until week 24 of follow up. There was no difference in outcomes or trough

关键词： Inflammatory bowel disease   Irritable bowel syndrome   FODMAP   Mast cell   Ischemia  

摘要： Functional bowel symptoms can be occurred during remission from inflammatory bowel disease. In this case, a low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet is effective for the amelioration or prevention of symptoms. However, the reason is not fully explained. This report proposes a hypothesis regarding the entire process in which inflammatory bowel disease with IBS-like symptoms (IBD-IBS) causes symptoms. A detailed process was assumed, starting from high pressure in the lumen and finally to abdominal symptoms. In this process, relationships were linked based on interactions such as ischemia, compliance, pain threshold, visceral hypersensitivity, mast cells, and permeability reported in IBD-IBS. In the process mapping, to understand the relationship between the amount of gas increased by FODMAP and ischemia, the hydrodynamic hypothesis and Ritchie's hypothesis were adapted. Ischemia in dilated intestines due to an increase in gas volume can induce excessive spasms via the mast cells and show the whole process of lowering the pain threshold. From the standpoint of the mechanism of IBD-IBS, the origin trigger may be FODMAP. Therefore, a low-FODMAP diet is recommended to relieve and prevent IBD-IBS symptoms.

关键词： Association (Psychology)   Arthritis   Inflammatory Bowel Diseases   Authority   Intestinal Diseases  

摘要： However, a recent routine screening colonoscopy and subsequent biopsy showed severe active inflammation with ulcerations characteristic of Crohn's disease. 4 Adarsh MB, Dogra S, Vaiphei K, Vaishnavi C, Sinha SK, Sharma A. Evaluation of subclinical gut inflammation using fecal calprotectin levels and colonic mucosal biopsy in psoriasis and psoriatic arthritis patients. [Extracted from the article]

关键词： Antibiotics   Clostridium difficile   inflammatory bowel disease   risk factors   Turkey  

摘要： Background / Aims: Clostridium difficile is a Gram-positive, strict anaerobe, spore-forming bacterium. It can cause self-limiting mild diarrhea, severe diarrhea, pseudomembranous colitis, and fatal fulminant colitis. We aimed to investigate the changes in epidemiology and incidence of C. difficile infection in our hospital database. Patients and Methods: Episodes of C. difficile toxin were identified in hospital database, and data such as age, sex, community versus hospital acquisition, intensive care follow-up, current or previous treatments with antibiotics within the past 3 months, medication with proton pump inhibitors, or immunosuppressive therapies were collected. Results: Toxin-positive 78 individuals constituted the patient group. In univariate analyses, independent risk factors for toxin positivity were community versus hospital acquisition [odds ratio (OR), 5.49;95% confidence interval (CI), 2.52-11.95;P = 0.0001], presence of inflammatory bowel diseases (IBDs) (OR, 21.5;95% CI, 8.65-53.44;P = 0.0001), proton pump inhibitors' use (OR, 4.53;95% CI, 1.97-10.43;P = 0.0001), immunosuppressive drug use (OR, 4.1;95% CI, 2.01-8.3;P = 0.0001), and use of quinolone group of antibiotics (OR, 5.95;95% CI, 1.92-18.46;P = 0.001). Antibiotic use was a protective risk factor (OR, 0.09;95% CI, 0.01-0.78;P = 0.01) and presence of IBDs was an independent risk factor (OR, 6.8;95% CI, 1.5-30.08;P = 0.01) in community-acquired group (OR, 0.09;95% CI, 0.01-0.78;P = 0.01). Conclusion: In recent studies, C. difficile infections were demonstrated to be more frequent in younger individuals who did not have a history of hospitalization but had an underlying disease such as IBD. In our study, we showed the change in the epidemiological data with prominence of underlying diseases such as IBDs.