Causes of inflammatory bowel diseases are not well understood and the most prominent forms, Crohn’s disease (CD) and ulcerative colitis (UC), are sometimes hard to distinguish. Glycosylation of IgG ...has been associated with CD and UC. IgG Fc-glycosylation affects IgG effector functions. We evaluated changes in IgG Fc-glycosylation associated with UC and CD, as well as with disease characteristics in different patient groups.
We analyzed 3441 plasma samples obtained from 2 independent cohorts of patients with CD (874 patients from Italy and 391 from the United States) or UC (1056 from Italy and 253 from the US and healthy individuals controls; 427 in Italy and 440 from the United States). IgG Fc-glycosylation (tryptic glycopeptides) was analyzed by liquid chromatography coupled to mass spectrometry. We analyzed associations between disease status (UC vs controls, CD vs controls, and UC vs CD) and glycopeptide traits, and associations between clinical characteristics and glycopeptide traits, using a logistic regression model with age and sex included as covariates.
Patients with CD or UC had lower levels of IgG galactosylation than controls. For example, the odds ratio (OR) for IgG1 galactosylation in patients with CD was 0.59 (95% confidence interval CI, 0.51–0.69) and for patients with UC was 0.81 (95% CI, 0.71–0.92). Fucosylation of IgG was increased in patients with CD vs controls (for IgG1: OR, 1.27; 95% CI, 1.12–1.44), but decreased in patients with UC vs controls (for IgG23: OR, 0.72; 95% CI, 0.63–0.82). Decreased galactosylation associated with more severe CD or UC, including the need for surgery in patients with UC vs controls (for IgG1: OR, 0.69; 95% CI, 0.54–0.89) and in patients with CD vs controls (for IgG23: OR, 0.78; 95% CI, 0.66–0.91).
In a retrospective analysis of plasma samples from patients with CD or UC, we associated levels of IgG Fc-glycosylation with disease (compared to controls) and its clinical features. These findings could increase our understanding of mechanisms of CD and UC pathogenesis and be used to develop diagnostics or guide treatment.
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Neoangiogenesis and increased endothelial permeability are observed as results of chronic intestinal inflammation. However, limited data on microvascular and crypt architecture during remission ...phases is available. The aim of this prospective investigator blinded cohort study was to assess crypt and microvascular architecture and function in ulcerative colitis by probe based confocal laser endomicroscopy; we also evaluated whether these findings may have the potential to predict disease relapse.
19 ulcerative colitis patients in clinical and endoscopic remission and 19 controls were studied. A computer based image processing technique was applied to construct 20 mosaicing image sets from each subject. Remitting patients were sub-grouped into either inactive or quiescent disease according to histology.
Pericrypt fluorescence (p<0.01), crypt diameter (p<0.05) but not intercrypt distance (p=0.07) were significantly increased in ulcerative colitis patients compared to controls. Patients with inactive disease showed a significant increase in fluorescence leakage (median fluorescence (IQR), 3888 (3560–4240) vs. 2696 (2502–3390), p<0.01), crypt diameter (median diameter (IQR), 92.5 (85.5–101) vs. 73 (70–77), p<0.05) and intercrypt distance (median distance (IQR), 82.5 (70.5–91.2) vs. 66 (59.5–73.5), p<0.05) compared to those with quiescent disease. A composite outcome score combining fluorescence leakage and crypt diameter was able to predict a disease flare during a 12month follow-up period (p<0.01).
In vivo intramucosal changes detected by confocal endomicroscopy in ulcerative colitis remittent patients can predict disease relapse. This observation may have further implications for disease management and medical treatment.
Assessing the clinical course of inflammatory bowel disease (IBD) patients consists of periodical clinical evaluations and laboratory tests. We aimed to assess the role of calprotectin tests in ...predicting clinical relapse in IBD patients.
Ninety-seven patients with ulcerative colitis (UC) and 65 with Crohn's disease (CD) in clinical remission were prospectively included in the study. A 10-g stool sample was collected for calprotectin assay. The cutoff level was set at 130 mg/kg of feces. Patients were followed up for 1 yr after the test or until relapse. The cumulative proportion of relapses was estimated by the Kaplan-Meier analysis. Statistics for equality of survival distribution were tested using the log-rank test.
The calprotectin test was positive in 44 UC patients and 26 of them relapsed within a year, while 11 of 53 UC patients with a negative calprotectin test relapsed within the same time frame. Thirty CD patients had a positive calprotectin test and 13 of them relapsed within a year, as did 7 of the 35 with a negative test result. A significant correlation emerged between a positive calprotectin test and the probability of relapse in UC patients (P= 0.000). In CD patients, only cases of colonic CD showed a significant correlation between a positive calprotectin test and the probability of relapse, i.e., 6 colonic CD patients were positive for the calprotectin test and 4 relapsed (P= 0.02).
Measuring calprotectin may help to identify UC and colonic CD patients at higher risk of clinical relapse.
Background Our aim was to assess the relationship between the ileal-pouch microbiota and inflammatory parameters in patients operated on for ulcerative colitis. Methods In this cross-sectional study, ...32 consecutive outpatients returning for follow-up endoscopy were recruited. Pouch biopsies were obtained during endoscopy for culture of bacteria adherent to the mucosa, histology, and analysis of local inflammation (IL-1β, IL-6, and TNFα by immunometric assay; and toll--like receptor TLR 2 and 4 mRNA by quantitative real-time PCR). Fecal samples were collected for analysis of lactoferrin by ELISA. Results Granulocyte and monocyte mucosal infiltration correlated directly with mucosal Bacteriodiaceae spp. counts. Clostridiaceae spp. counts showed a direct correlation with mucosal ulceration and number of daily stools. In patients with pouchitis, Enterococcaceae spp. counts were less than in healthy patients. Enterobacteriaceae spp., Streptococcaceae spp. and Enterococcaceae spp. counts correlated inversely with immune cell infiltration. TLR-2 and TLR-4 mRNA, and mucosal levels of IL-1β levels all correlated directly with Veilonella spp. counts. Conclusion Bacteriodaceae spp. and, Clostridiaceae spp. may be associated with inflammation of the pouch mucosa. Conversely, Enterococcaceae spp., and possibly Enterobacteriaceae spp. and Streptococcaceae spp., may have an active role in maintaining immunologic homeostasis within the pouch mucosa.
Biological agents such as inhibitors of tumour necrosis factor alpha (TNF-alpha ) are associated with the development of opportunistic infections. Although there are no international recommendations ...for the management of opportunistic infections, their prevention is a key safety issue for patients with inflammatory bowel disease (IBD). We report that chemoprophylaxis with oral valaciclovir was effective in preventing Herpes simplex virus (HSV-1) reactivation in a girl treated with infliximab for Crohn's disease.
The cost of caring for patients with inflammatory bowel disease (IBD) continues to increase worldwide. The cause is not only a steady increase in the prevalence of Crohn's disease and ulcerative ...colitis in both developed and newly industrialised countries, but also the chronic nature of the diseases, the need for long-term, often expensive treatments, the use of more intensive disease monitoring strategies, and the effect of the diseases on economic productivity. This Commission draws together a wide range of expertise to discuss the current costs of IBD care, the drivers of increasing costs, and how to deliver affordable care for IBD in the future. The key conclusions are that (1) increases in health-care costs must be evaluated against improved disease management and reductions in indirect costs, and (2) that overarching systems for data interoperability, registries, and big data approaches must be established for continuous assessment of effectiveness, costs, and the cost-effectiveness of care. International collaborations should be sought out to evaluate novel models of care (eg, value-based health care, including integrated health care, and participatory health-care models), as well as to improve the education and training of clinicians, patients, and policy makers.
Patients affected by Crohn's disease (CD) require lifelong medical therapy, but they can also often require abdominal surgery. The effect of CD therapy on postoperative course is still unclear. The ...aim of this study was to evaluate the effect of preoperative medical therapy on the outcome of intestinal surgery in these patients.
Data from a consecutive series of 167 patients with CD operated on at the University of Padova Hospital from 2000 to 2013 were retrieved. Data of preoperative therapy during the 6 months before surgery were available for 146 patients who were enrolled in this retrospective study. Clinical data and surgical details were retrieved and postoperative complications and reoperation were considered outcome measures. Univariate and multivariate analysis were performed.
No significant difference was observed between patients without data about their preoperative therapy and those with them. Eight patients underwent reoperation in the first 30 postoperative days: two of them for anastomotic leak, three for bleeding, one for obstruction and two for abdominal wound dehiscence. At multivariate analysis, preoperative adalimumab and budesonide resulted to be an independent predictor of reoperation (OR = 7.67 (95% CI = 1.49-39.20), p = 0.01 and OR = 6.7749 (95% CI = 0.98-46.48), p = 0.05, respectively). At multivariate analysis neither pharmacological nor clinical variables resulted to predict anastomotic leak.
In our series, adalimumab seemed to be associated to early reoperation after intestinal surgery. This may be due to a worst disease severity in patients who needed surgery in spite of biological therapy. Preoperative tapering of budesonide dose seems a safe option before elective abdominal surgery for CD.
Crohn's disease and ulcerative colitis have a feature in common (i.e., chronic inflammation). Their clinical management requires repeated assessments; endoscopy with histological examination remains ...the gold standard for detecting and quantifying intestinal inflammation. An ideal marker should be quick and easy to obtain noninvasively, and should be inexpensive and reproducible. Several laboratory tests have been studied but, to date, a disease marker is not yet available. A combination of signs and symptoms, laboratory findings and imaging techniques is consequently still needed for assessing disease activity and prognosis. In recent years, research has drawn attention to fecal markers owing to their specificity for intestinal inflammation, ease of sample collection, availability of commercial immunoassays and convenience. Biological markers have been used to assess inflammatory bowel disease patients for the purposes of their clinical management, monitoring disease activity, predicting relapses, assessing prognosis and monitoring response to treatment.
This study was designed to assess the role of fecal lactoferrin and calprotectin as markers of intestinal inflammation in patients with Crohn's disease who have undergone ileocolonic resection.
...Sixty-three patients who had undergone ileocolonic resection for Crohn's disease with a median follow-up of 40.5 (range, 5-102) months were enrolled. Clinical examination and blood test were performed, and fecal lactoferrin and calprotectin levels were dosed. The predictors for fecal lactoferrin and calprotectin levels that resulted to be significant at the univariate analyses were included in two multiple regression analysis models.
The mean lactoferrin level was 21 +/- 3.9 microg/g and the mean calprotectin fecal level was 247 +/- 22.7 ng/ml. C-reactive protein levels (P < 0.01), calprotectin levels (P < 0.01), and the presence of clinical recurrence (P = 0.04) resulted to be independent predictors of lactoferrin levels. Only lactoferrin levels resulted to be an independent predictor for calprotectin fecal levels (P < 0.01).
Crohn's disease patients maintain high fecal levels of lactoferrin and calprotectin at long-term follow-up after resection of the diseased bowel even in case of clinical remission. The significant correlation between the two fecal markers may be the expression of the ongoing intestinal inflammation. Only lactoferrin significantly correlated with C-reactive protein and showed a reliable threshold value for systemic inflammation. Lactoferrin fecal levels may be a reliable indicator for intestinal inflammation influencing the systemic inflammatory status. The third predictor of lactoferrin fecal level was the presence of episodes of clinical recurrence during the postoperative follow-up.
Maintenance of medically induced remission is a clinical challenge in Crohn's disease (CD), since it is a chronic disease and that often occurs in young people. The introduction of immunosuppressors ...and biologics has significantly improved the management of these patients, however efficacy and safety of these treatments in the very long term still needs clarification. Furthermore, scientific research is driven more into new drugs to induce remission rather then maintenance.
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