Ulcerative Colitis Disease Patients Research Articles

Intestinal Epithelial Cells Adapt to Chronic Inflammation through Partial Genetic Reprogramming.

Reactive oxygen species (ROS) are considered to be the main drivers of inflammatory bowel disease. We investigated whether this permanent insult compels intestinal stem cells to develop strategies to dampen the deleterious effects of ROS. As an adverse effect, this adaptation process may increase their tolerance to oncogenic insults and facilitate their neoplastic transformation. We submitted immortalized human colonic epithelial cells to either a mimic of chronic inflammation or to a chemical peroxide, analyzed how they adapted to stress, and addressed the biological relevance of these observations in databases. We demonstrated that cells adapt to chronic-inflammation-associated oxidative stress in vitro through a partial genetic reprogramming. Through a gene set enrichment analysis, we showed that this program is recurrently active in the intestinal mucosae of Crohn's and ulcerative colitis disease patients and evolves alongside disease progression. Based on a previously reported characterization of intestinal stem and precursor cells using tracing experiments, we lastly confirmed the activation of the program in intestinal precursor cells during murine colorectal cancer development. This adaptive process is thus likely to play a role in the progression of Crohn's and ulcerative disease, and potentially in the initiation of colorectal cancer.

Endocytoscopy for assessing histologic inflammation in ulcerative colitis: development and prospective validation of the ELECT (ErLangen Endocytoscopy in ColiTis) score (with videos)

Apart from endoscopic healing as an established treatment goal in patients with inflammatory bowel disease (IBD), histologic remission is an emerging endpoint that might even better predict disease outcome, especially in ulcerative colitis (UC). Within this study, we aimed to evaluate whether endocytoscopy (EC) as an invivo contact microscopy technology can accurately assess histologic inflammation and predict the further course of disease in UC patients. Initially, a new and intuitive EC score reflecting the entire spectrum of microscopic disease activity in UC was consensually developed. Subsequently, this score was independently validated in 46 patients with UC who underwent close-meshed follow-up during which major adverse outcomes (MAOs; defined as disease flare, IBD-related hospitalization, IBD-related surgery, necessity for initiation or escalation therapy) were recorded. Results of EC grading of inflammatory activity were compared against 2 validated histologic scores in UC. Diagnostic performance of endoscopic remission under white-light endoscopy (Mayo Endoscopic Score and Ulcerative Colitis Endoscopic Index of Severity), EC, and histology were compared for the prediction of MAOs. Endocytoscopic assessment of inflammatory activity in UC based on the newly developed ErLangen Endocytoscopy in ColiTis score showed strong correlation with histopathologic scoring (Robarts Histopathology Index, r= .70; Nancy Histologic Index, r= .73) and was superior to white-light endoscopy for grading of microscopic disease activity, with a sensitivity of 88%, specificity of 95.2%, and area under the curve of .916. Furthermore, EC exhibited a high interobserver agreement for invivo grading of microscopic inflammation and was comparably accurate as histopathology for forecasting the occurrence of MAOs in UC. Endocytoscopic grading of inflammatory activity along a newly developed scoring system enabled real-time histology in UC patients and better predicted clinical outcome in UC patients than endoscopic remission.

Effects of saffron supplementation on oxidative/antioxidant status and severity of disease in ulcerative colitis patients: A randomized, double-blind, placebo-controlled study.

Supplementation with saffron helps improve antioxidant status. Oxidative stress plays an important role in ulcerative colitis (UC). The present study aimed to investigate the effect of saffron supplementation on disease severity and Oxidative/Antioxidant factors in patients with UC. This randomized double-blinded study was conducted on 80 mild to moderate UC patients. Participants were randomly divided into intervention (100 mg saffron/daily) and placebo (100 mg maltodextrin/daily) groups. Of all the participants, 75 completed the study. After 8 weeks, there were significantly increased in the mean score of simple clinical colitis activity index questionnaire (3.83 ± 1.78 to 3 ± 1.60, p = .004), the serum levels of total antioxidant capacity (2.68 ± 0.90 to 2.79 ± 0.87, p = .016), superoxide dismutase (60.69 ± 9.59 to 66.30 ± 10.79, p = .009) and glutathione peroxidase (22.05 ± 14.27 to 29.67 ± 17.97, p = .011) in patients received saffron compared to the placebo group. Whereas, there was no significant difference in serum levels of malondialdehyde between the two groups. Finally, dietary saffron as an alternative therapy may effective in improving antioxidant factors and reducing the severity of disease in UC patients.

Metabolic bone disease in children and adolescent patients with ulcerative colitis

ObjectiveMetabolic bone disease concerns a broad spectrum of conditions related to reduced bone density. Metabolic bone disease has been linked to chronic inflammatory diseases, such as ulcerative colitis. This study examines the prevalence of metabolic bone disease in ulcerative colitis patients and explores possible clinical predictors. MethodThe authors performed a retrospective study involving children and adolescents with confirmed ulcerative colitis between January 2013 and December 2018. Bone density was evaluated through a dual-energy X-ray absorptiometry scan of the spine and total body. Osteoporosis was defined as a bone mineral density Z-score of <−2 and osteopenia as a Z-score of between −1.0 and −2. ResultsA total of 37 patients were included in this analysis, with a mean age of 13.4±3.9 years and a mean duration of illness of 2.1±2.4 years. Using lumbar spine Z-scores and total body Z-scores, osteoporosis and osteopenia were identified by dual-energy X-ray absorptiometry scan measurements in 11 patients (29.7%) and 15 patients (40.5%), and in ten patients (27%) and 13 patients (35%), respectively. Lumbar spine Z-scores were significantly positively associated with male gender (B=2.02; p=0.0001), and negatively associated with the presence of extraintestinal manifestations (B=−1.51, p=0.009) and the use of biologics (B=−1.33, p=0.004). However, total body Z-scores were positively associated with body mass index Z-scores (B=0.26, p=0.004) and duration of illness in years (B=0.35, p=0.003). ConclusionsMetabolic bone disease is very common in this cohort of Saudi Arabian children and adolescents with ulcerative colitis and its occurrence appears to increase in female patients who suffer from extraintestinal manifestations.

P087 Biomarkers of elastin degradation differentiate between clinically inactive and active disease in ulcerative colitis patients

Abstract Background In ulcerative colitis (UC), the state of chronic inflammation results in increased matrix metalloprotease (MMP) and serine protease activity, which effectively leads to a higher degree of intestinal tissue remodelling, including components of the extracellular matrix (ECM). One of these components is elastin a matrix protein of the interstitial matrix in the lamina propria and submucosa, providing tissue resilience and elasticity. As such, we investigated whether elastin degradation in UC patients was associated with disease activity and severity, potentially enabling patient differentiation based on elastin degradation. Methods Twenty-nine UC patients and 29 healthy donors were included in the study. Disease activity was determined according to the partial Mayo score (pMayo &amp;gt;1) and the Mayo Endoscopic Score (MES). Disease severity and extension was assessed using the Montreal classification. Disease severity was additionally assessed using the Trulove and Witt’s (TW) clinical score. The biomarkers of elastin degradation included: MMP-7 (ELM-7) cathepsin-G (EL-CG) and proteinase-3 (ELP-3), measured in serum by ELISA. One-way ANOVA (Kruskal–Wallis) correcting for the false discovery rate were applied for the statistical analysis. Results TW: ELP-3 levels in moderate-to-severe UC patients were significantly elevated in comparison with HD (p &amp;lt; 0.001). Partial Mayo: EL-CG levels in patients with active UC were significantly elevated in comparison with HD (p &amp;lt; 0.01), and UC patients in remission (p &amp;lt; 0.01). ELP-3 levels were likewise significantly elevated in active UC patients compared with HD (p &amp;lt; 0.001), and UC patients in remission (p &amp;lt; 0.01). Montreal classification: ELM-7 was significantly elevated in active UC compared with HD (p &amp;lt; 0.05), and UC patients in remission (p &amp;lt; 0.05). EL-CG were also significantly elevated in active UC compared with HD (p &amp;lt; 0.05), and UC patients in remission (p &amp;lt; 0.05). ELP-3 was significantly elevated in active UC compared with HD (p &amp;lt; 0.01). According to the MES score, ELP-3 levels in moderate-to-severe UC patients were significantly elevated in comparison to HD (p &amp;lt; 0.01). Conclusion The data presented in this study demonstrate an association between biomarkers of proteolytic elastin degradation and disease activity in UC patients especially the protease-3-derived biomarker, ELP-3, showed significant association with active UC in all the clinical scoring systems as well as the MES score. Utilising these minimally invasive elastin degradation biomarkers could serve as surrogate markers for monitoring of disease activity and potentially aid the differentiation of patients with an active disease from patients in remission or with a lower disease activity for UC.

Atrial peak longitudinal strain may be predictive of pancolitis in patients with ulcerative colitis.

Ulcerative colitis is a chronic idiopathic inflammatory bowel disease of the colon that is characterized by a relapsing and remitting course. Previous studies have shown that arterial stiffness, carotid intima media thickness, atrial electromechanical delay, and global longitudinal strain suggested subclinical cardiovascular disorders in ulcerative colitis patients. The aims of our study was to evaluate the left atrial function of patients with ulcerative colitis by using speckle tracking echocardiography, and to assess the relationship between echocardiographic variables and the extent of the disease. We recruited 51 outpatients with ulcerative colitis in remission phase and 52 healthy volunteers. The ulcerative colitis patients were evaluated by for the extent of the disease by endoscopy at the initial diagnosis. E/Em , left atrial volume, and left atrial stiffness index were higher, and peak atrial longitudinal strain was lower in pancolitis than in non-pancolitis patients. In the multivariate logistic regression test, peak atrial longitudinal strain and E/Em were found to be independent predictors for pancolitis. Early detection of myocardial abnormalities by conventional echocardiography and speckle tracking echocardiography, which is a simple and non-invasive technique, may be useful for giving insights to the extent of the disease in ulcerative colitis patients.

P600. Safety and efficacy of infliximab biosimilar (Remsima©) in ulcerative colitis disease patients in clinical practice: results after 6-months treatment

P600. Safety and efficacy of infliximab biosimilar (Remsima©) in ulcerative colitis disease patients in clinical practice: results after 6-months treatment

Fecal calprotectin is a useful marker to diagnose ulcerative colitis from irritable bowel syndrome.

Background:This study was aimed to evaluate the predictive value of fecal calprotectin in patients with ulcerative colitis from patients with irritable bowel syndrome (IBS).Materials and Methods:Between May and October 2013, 88 adult patients, between the age 18 and 65 years with a history of chronic diarrhea of unknown origin were assessed. Standard colonoscopies were performed in all patients to assess ulcerative colitis. Before colonoscopies, they were asked to supply a stool specimen. Fecal calprotectin value was measured using a commercial enzyme-linked immunosorbent assay kit.Results:The mean of age, gender combination, and body mass index were not significantly different between patients with ulcerative colitis or IBS. The duration of disease in ulcerative colitis patients was significantly higher than IBS patients (P < 0.0001). The level of calprotectin in ulcerative colitis patients was significantly higher than IBS patients (265.9 vs 115.8, respectively, P = 0.001). Also, cutoff value >164 μg/g with sensitivity and specify of 57 (CI: 41%–71.6%), and 75 (CI: 59.7%–56.8%), respectively, was the best for discrimination between patients with ulcerative colitis and those with IBS.Conclusion:Our results show that fecal calprotectin as a noninvasive method, which can be used to identify patients with ulcerative colitis from IBS patients has low sensitivity and specificity.

Association of vitamin D receptor gene polymorphisms with the susceptibility to ulcerative colitis in patients from Southeast China

The association studies from different ethnic groups showed that vitamin D receptor (VDR) gene polymorphisms might be connected with the susceptibility to ulcerative colitis (UC); however, the conclusions were less consistent. Our study aimed to analyze the associations of UC with common mutations of VDR in Chinese patients. A total of 382 UC patients and 489 healthy controls were recruited. The genotypes of VDR FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236) were examined by SNaPshot assays. Haplotype analysis was performed in all study subjects. After Bonferroni correction, the mutant alleles and genotypes of VDR FokI, BsmI, ApaI and TaqI did not statistically differ between UC patients and the controls (all p > 0.0125). However, the mutant allele C and genotype TC + CC of FokI gene were significantly increased in patients with mild and moderate UC compared to those with severe UC (C allele: 54.1% versus 39.3%, OR = 1.83, 95% CI: 1.21–2.75, p = 0.004; TC + CC genotype: 81.6% versus 57.1%, OR = 3.32, 95% CI: 1.83–6.06, p < 0.001, respectively). Haplotype analysis showed that the VDR BsmI, ApaI and TaqI polymorphic loci were in a strong linkage disequilibrium. Furthermore, the frequency of AAC haplotype was statistically lower in UC patients than that in the controls (3.8 versus 5.9%, OR = 0.63, 95% CI: 0.39–1.01, p = 0.039). In conclusion, the mutation of FokI gene influenced severity of the disease in UC patients. Moreover, the AAC haplotype formed by the VDR BsmI, ApaI and TaqI gene might engender a reduced risk of UC attack.

How fast up the ladder? Factors associated with immunosuppressive or anti-TNF therapies in IBD patients at early stages: results from a population-based cohort.

With the introduction of anti-TNF therapies in the treatment of IBD, the therapeutic strategies have changed to an accelerated step-up care to avoid long-term complications. Little is known about the implementation of these strategies into daily care. We aimed to evaluate this question and to identify factors associated with the early use of immunosuppressants or anti-TNF therapies in a population-based IBD cohort. Patients with an IBD diagnosed between January 2004 and December 2008 were included. Medical therapies were evaluated at first diagnosis and during a 5-year follow-up. Risk factors associated with the initiation of an immunosuppressive therapy were assessed. Two hundred and forty-one patients were evaluated (145 Crohn's disease (CD), 96 ulcerative colitis (UC)). An immunosuppressive or anti-TNF therapy was started in 83 CD (57.2 %) and 40 UC (43 %) patients (p = 0.033, relative risks (RR) 1.77; 95 % confidence interval (CI) 1.05-3.0). After 5 years, 38.8 % CD patients on immunosuppressive therapy were treated with anti-TNF therapies. The use of corticosteroids at first diagnosis, disease localization and surgery were independent predictors for an immunosuppressive or anti-TNF therapy in CD. In UC, the extension of disease was associated with immunosuppressive therapies. The use of steroids and localization in CD patients and an extended disease in UC patients affected the time until an immunosuppressive therapy was started. We found a high proportion of patients using an immunosuppressive therapy during the early course. Therefore, the accelerated step-up strategy seems to be successfully implemented in the daily care of IBD patients. We were able to identify several factors associated with an immunosuppressive or anti-TNF therapy in CD and UC.

Family history of inflammatory bowel disease among patients with ulcerative colitis: A systematic review and meta-analysis

Background and aimsDespite numerous shared susceptibility loci between Crohn's disease and ulcerative colitis, the prevalence of family history among ulcerative colitis patients is not well-established and considered to be less prevalent. A systemic review and meta-analysis were conducted to estimate the prevalence of family history of inflammatory bowel disease in ulcerative colitis patients, and its effect on disease outcomes. MethodsPubMED was searched to identify studies reporting the prevalence of family history of inflammatory bowel disease among ulcerative colitis patients. Definitions of family history, study type, and subtypes of family history prevalence were abstracted, as were disease outcomes including age at ulcerative colitis diagnosis, disease location, surgery and extraintestinal manifestations. Pooled prevalence estimates were calculated using random effects models. ResultsSeventy-one studies (86,824 patients) were included. The prevalence of a family history of inflammatory bowel disease in ulcerative colitis patients was 12% (95% confidence interval [CI] 11 to 13%; range 0–39%). Family history of ulcerative colitis (9%; 22 studies) was more prevalent than Crohn's disease (2%; 18 studies). Patients younger than 18years of age at time of diagnosis had a greater family history of inflammatory bowel disease (prevalence 15%, 95% CI: 11–20%; 13 studies). There were no differences in disease location, need for surgery, or extraintestinal manifestations among those with a family history, although very few studies reported on these outcomes. ConclusionsOverall, 12% of ulcerative colitis patients have a family history of inflammatory bowel disease, and were more likely to have a family history of ulcerative colitis than Crohn's disease. Pediatric-onset ulcerative colitis patients were more likely to have a family history of inflammatory bowel disease.

A risk of difficult to treat disease in ulcerative colitis patients exists even with normal serology antibody assay values

A risk of difficult to treat disease in ulcerative colitis patients exists even with normal serology antibody assay values

Do Patients with Ulcerative Colitis Diagnosed at a Young Age Have More Severe Disease Activity than Patients Diagnosed when Older?

Background/Aims: To compare the clinical features and disease behavior of ulcerative colitis (UC) according to the age at onset. Methods: This retrospective study included 455 patients with UC who were diagnosed and treated between 1990 and 2008 at a single tertiary institution in Korea. The patients were divided into 2 groups according to their age at diagnosis of UC: an elderly group (≧40 years) and a young group (<40 years). Clinical findings at diagnosis, extent of disease, treatment modalities used, cumulative admission rates, cumulative relapse rates, and surgery rates were analyzed according to these age groups. Results: Two hundred and forty-two patients with UC (53.2%) were diagnosed before the age of 40 years. Disease severity at initial presentation as assessed by diarrhea frequency, the presence of pancolitis, and the use of steroids were higher in the young group; however, clinical disease course including cumulative admission rates, cumulative relapse rates, and surgery rates were not significantly different between the 2 groups. Conclusions: Certain clinical features and the extent of disease in UC patients appear to be more severe when the disease is diagnosed at younger age; however, their disease course and prognosis might not be different from those of their older counterparts.

Lamina propria and circulating interleukin-6 in newly diagnosed pediatric inflammatory bowel disease patients.

Understanding cytokine production patterns in early mucosal lesions of pediatric patients newly diagnosed with inflammatory bowel disease (IBD) may be critical to understanding IBD pathogenesis. Interleukin-6 (IL-6) has a central role in a multitude of immune system reactions; however, inconsistent lamina propria and serum IL-6 has been reported in IBD patients. Newly diagnosed pediatric IBD patients have not previously been evaluated for lamina propria or serum IL-6. Serum and intestinal lamina propria biopsy whole organ culture supernatants were evaluated by ELISA for IL-6 obtained from newly diagnosed IBD patients, before initiation of immunomodulatory therapies. Levels of lamina propria IL-6 demonstrated significant correlation with graded severity of histological inflammation (p < 0.001). Log-transformed serum and organ culture IL-6 levels demonstrated significant correlation (p < 0.0001, R2 = 0.6226). Assigning a demarcation level of >400 pg/ml, serum IL-6 concentrations were a superior marker for the presence of microscopic intestinal inflammation than erythrocyte sedimentation rate (ESR), with a sensitivity of 82%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 82%. When evaluating subtypes of IBD, serum IL-6 levels were correlated more significantly with active disease in ulcerative colitis patients (p = 0.01, R2 = 0.74) than in Crohn's disease patients (p = 0.21, R2 = 0.33). This study outlines graded production of IL-6 in intestinal lamina propria and serum of newly diagnosed pediatric IBD patients, confirming the presence of IL-6 in early IBD patients. In addition, serum IL-6 may be a good predictor of IBD in pediatric patients with suspected or newly diagnosed IBD.

Lamina propria and circulating interleukin-6 in newly diagnosed pediatric inflammatory bowel disease patients

OBJECTIVES: Understanding cytokine production patterns in early mucosal lesions of pediatric patients newly diagnosed with inflammatory bowel disease (IBD) may be critical to understanding IBD pathogenesis. Interleukin-6 (IL-6) has a central role in a multitude of immune system reactions; however, inconsistent lamina propria and serum IL-6 has been reported in IBD patients. Newly diagnosed pediatric IBD patients have not previously been evaluated for lamina propria or serum IL-6. METHODS: Serum and intestinal lamina propria biopsy whole organ culture supernatants were evaluated by ELISA for IL-6 obtained from newly diagnosed IBD patients, before initiation of immunomodulatory therapies. RESULTS: Levels of lamina propria IL-6 demonstrated significant correlation with graded severity of histological inflammation ( p < 0.001). Log-transformed serum and organ culture IL-6 levels demonstrated significant correlation ( p < 0.0001, R 2 = 0.6226). Assigning a demarcation level of >400 pg/ml, serum IL-6 concentrations were a superior marker for the presence of microscopic intestinal inflammation than erythrocyte sedimentation rate (ESR), with a sensitivity of 82%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 82%. When evaluating subtypes of IBD, serum IL-6 levels were correlated more significantly with active disease in ulcerative colitis patients ( p = 0.01, R 2 = 0.74) than in Crohn’s disease patients ( p = 0.21, R 2 = 0.33). CONCLUSIONS: This study outlines graded production of IL-6 in intestinal lamina propria and serum of newly diagnosed pediatric IBD patients, confirming the presence of IL-6 in early IBD patients. In addition, serum IL-6 may be a good predictor of IBD in pediatric patients with suspected or newly diagnosed IBD.