Association between the ulcerative colitis endoscopic index of severity (UCEIS) and outcomes in acute severe ulcerative colitis.

BACKGROUND: The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) accounts for 86% of the variance between observers in the overall assessment of endoscopic severity, but has not been correlated with outcomes. METHODS: Consecutive cases of acute severe colitis (ASC) defined by Truelove and Witts (TW) criteria were retrospectively evaluated. Demographic details, number of TW criteria, prior medical therapy, UCEIS and inpatient medical therapy were recorded. Pre-specified (adverse) endpoints included rescue therapy, colectomy and readmission. RESULTS: Eighty-nine patients, 48 (54%) male, mean age 38 years, all received intravenous hydrocortisone 400mg/d (median 5 days [range 1-11]). Median follow-up was 14 months (2-33). Forty-eight (54%) were diagnosed the year prior to or at the time of admission. Thirty-six (40%) required rescue therapy (infliximab 25/36, ciclosporin 12/36, one receiving both). Twenty-one (24%) underwent colectomy on the index admission (9/21) or during follow-up (12/21). Median UCEIS score (possible range 0-8) was 5 (3-8). UCEIS was higher in patients requiring rescue therapy or colectomy (median score 6 [range 4-8] versus 5/8 [3-8], both p < 0.005). For UCEIS ≥5, 27/54 (50%) required rescue therapy, compared with 9/33 (27%) for UCEIS ≤4 (p = 0.037). When UCEIS was ≥5, 18/54 (33%) came to colectomy during follow-up, compared with 3/33 (9%) with UCEIS ≤4. Of 14 patients with UCEIS 7 or 8, 11/14 needed rescue therapy and 13/14 met any adverse endpoint. CONCLUSION: Endoscopic severity is associated with a worse outcome in ASC. When the UCEIS is ≥7 on admission, almost all patients will need treatment with infliximab or ciclosporin beyond steroids. This may mark a threshold for an early decision to use infliximab or ciclosporin.

The intracellular sensor NOD2 induces microRNA-29 expression in human dendritic cells to limit IL-23 release.

NOD2 is an intracellular sensor that contributes to immune defense and inflammation. Here we investigated whether NOD2 mediates its effects through control of microRNAs (miRNAs). miR-29 expression was upregulated in human dendritic cells (DCs) in response to NOD2 signals, and miR-29 regulated the expression of multiple immune mediators. In particular, miR-29 downregulated interleukin-23 (IL-23) by targeting IL-12p40 directly and IL-23p19 indirectly, likely via reduction of ATF2. DSS-induced colitis was worse in miR-29-deficient mice and was associated with elevated IL-23 and T helper 17 signature cytokines in the intestinal mucosa. Crohn's disease (CD) patient DCs expressing NOD2 polymorphisms failed to induce miR-29 upon pattern recognition receptor stimulation and showed enhanced release of IL-12p40 on exposure to adherent invasive E. coli. Therefore, we suggest that loss of miR-29-mediated immunoregulation in CD DCs might contribute to elevated IL-23 in this disease.

Inflammatory gene expression profiles in Crohn's disease and ulcerative colitis: a comparative analysis using a reverse transcriptase multiplex ligation-dependent probe amplification protocol.

BACKGROUND AND AIMS: Cytokines and their receptors play a critical role in the pathogenesis of the inflammatory bowel disease (IBD). The aim of this study was to investigate the expression profiles of inflammatory genes in inflamed and non-inflamed colonic tissue samples in patients with Crohn's disease (CD) and ulcerative colitis (UC), and to identify molecular signatures for different IBD phenotypes. METHODS: Seventy-one patients diagnosed with IBD (38 CD, 33 UC) and 15 non-IBD controls have been included in the study. For each patient, biopsy samples were obtained during colonoscopy from inflamed (L) and healthy (N) mucosa. We investigated by commercially available reverse-transcriptase multiplex ligation-dependent probe amplification (RT-MLPA) kit the mRNA expression of a set of 40 genes involved in inflammation: cytokines, chemokines, receptors, signal transduction molecules and transcription factors. RESULTS: In L biopsies from patients with CD, higher expression levels were found for IL-4 (p=0.009) and IL-12p35 (p=0.0005), whereas in L biopsy samples from patients with UC higher expression levels were found for IL-8 (p=0.03), chemokines SCYA3 (p=0.05), SCYA4 (p=0.01) and glutathione S-transferase P1 (p=0.01). In N biopsies of patients with CD higher expression levels were found for IL-1R (p=0.01) and IL-12p35 (p=0.007), whereas in N biopsies of patients with UC higher expression levels were found for IL-15 (p=0.009) and SCYA8 (p=0.001). The logistic regression analysis has indicated that low expression levels of IL-2 and IL-10, together with higher ASCA IgG titers were independently associated with penetrating/stricturing CD. CONCLUSIONS: RT-MLPA is a sensitive and effective method for the evaluation of the profiles of inflammatory genes in IBD, with potential future applications for diagnosis, phenotypic stratification and targeted therapy.

Higher titers of anti-Saccharomyces cerevisiae antibodies IgA and IgG are associated with more aggressive phenotypes in Romanian patients with Crohn's disease.

BACKGROUND AND AIMS: Serological markers have been widely used for diagnostic purposes and disease stratification in inflammatory bowel diseases (IBD). The aim of this study was to investigate the seroprevalence and the correlations of anti-Saccharomyces cerevisiae antibodies (ASCA) titers with different clinical phenotypes in Romanian patients with Crohn's disease (CD). METHODS: The study included 107 CD and 86 ulcerative colitis (UC) patients from the Gastroenterology Departments of three University Hospitals, and 60 healthy subjects. ASCA IgA and IgG titers were determined using ELISA test. For CD patients the phenotype was established according to the Montreal classification. The differences in ASCA titers for different CD phenotypes were assessed using the Mann-Whitney U test. RESULTS: ASCA prevalence was 33.6% in CD group, 12.8% in UC group and 6.6% in the control group. Significantly higher IgA (p=0.05) and IgG (p=0.03) titers were found in patients from the Montreal A1+A2 groups (age at onset below 40) compared with the older patients (A3). Higher titers were found in patients with extensive ileo-colonic lesions (L3) and upper gastrointestinal tract involvement (L4) than in patients having only colonic disease (L2). Significantly higher IgA (p=0.03) and IgG (p=0.03) titers were observed in patients with stenosing (B2) and penetrating (B3) disease compared with the nonstricturing, nonpenetrating (B1) phenotype. No correlation between ASCA titers and disease duration was found. CONCLUSION: ASCA seropositivity in Romanian CD patients is lower than in Western Europe. Higher ASCA IgA and IgG titers are associated with a younger age at diagnosis and more aggressive phenotypes.

Current epidemiologic trends in Crohn's disease: data from a tertiary referral centre in Bucharest: (Fundeni Institute, Center of Gastroenterology and Hepatology).

The purpose of this study was to estimate the incidence and prevalence of Crohn's disease (CD) in South-Muntenia, Bucharest-Ilfov and the Southwest region, using data collected from the main referral center in the area, during 2005-2009.Materials and methods A retrospective, descriptive study was conducted based on the 593 patients with CD admitted to the Center of Gastroenterology and Hepatology, Fundeni Institute, during this period. The incidence and the prevalence were reported per 100,000 inhabitants aged over 18.Results The incidence and the prevalence between 2005-2009 were estimated at 0.49 /100,000 and 1.88 / 100,000 inhabitants respectively. They both described an oscillating trend between 2005-2009, increasing in 2009 by 32% (p = 0.036) and by 69% (p = 0.000) respectively, as compared to 2005. The sex specific incidence rates was slightly, but not significantly, higher among women (0.59) than men (0.49). The average age at admission was 44. A bimodal age distribution was noticed with two peaks: between 30-39 and 50-59 years old. The highest incidence rate was found in the urban areas (1.09) and Bucharest (0.7). The temporal trend analysis showed that incidence of CD does not suffer significant changes over the interval 2010-2014, predicting an annual incidence rate of 0.52 / 100,000.Conclusion Data collected in the main referral center for the South-Muntenia, Bucharest-Ilfov and Southwest regions during the last five years confirms the previously described low frequency of CD in Romania, the bimodal age distribution and later onset of disease. The male to female ratio is close to unity, suggesting that men and women are generally at similar risk. There is a significant increase in both incidence and prevalence of CD when comparing 2005 with 2009. In term of predicting trends, the incidence of CD appears to be relatively stable, whereas the prevalence understandably rises over the interval 2010-2014. A further prospective multicenter study is necessary in order to assess the precise incidence, prevalence CD in Romania and to make more accurate predictions regarding future trends.