Disease Severity In Ulcerative Colitis Research Articles

Congenital abnormalities and other birth outcomes in children born to women with ulcerative colitis in Denmark and Sweden

Studies of women with ulcerative colitis (UC) during pregnancy have reported increased risks of preterm delivery, growth restriction, and congenital malformation. However, the results are inconsistent due to inadequate study design and limitations in sample size. We performed a population-based prevalence study on 2637 primiparous women with a UC hospital diagnosis prior to delivery and 868,942 primiparous women with no UC diagnosis in Denmark and Sweden, 1994-2006. Logistic regression analysis was used to estimate relative risks for moderately (32-36 weeks) and very (before 32 weeks) preterm birth, 5-minute Apgar score <7, small-for-gestational-age (SGA) birth, stillbirth, neonatal death, and congenital abnormalities. Maternal UC was associated with increased risk of moderately preterm birth (prevalence odds ratio [POR] 1.77, 95% confidence interval [CI]: 1.54-2.05), very preterm birth (POR 1.41, 95% CI: 1.02-1.96), cesarean section (POR 2.01, 95% CI: 1.84-2.19), and neonatal death (POR 1.93, 95% CI: 1.04-3.60). The strongest associations were observed for prelabor cesarean section (POR = 2.78, 95% CI: 2.38-3.25) and induced preterm delivery (POR 2.55, 95% CI: 1.95-3.33). There was a slightly increased risk of SGA birth (POR 1.27, 95% CI: 1.05-1.54). We found no association between UC and overall risk of congenital abnormalities (POR 1.05, 95% CI: 0.84-1.31) or specific congenital abnormalities. Risks for adverse birth outcomes were higher in women with previous UC-related surgery and hospital admissions. Women with UC have increased risks of preterm delivery, SGA-birth, neonatal death, and cesarean section but not congenital abnormalities. Adverse birth outcomes appeared correlated with UC disease severity.

Correlation of disease severity in ulcerative colitis with fecal MMP-9 levels, occludin, PAR-2 and PAR-4 mRNA expression in corresponding biopsies

Introduction: Active ulcerative colitis (UC) is characterized by tight junction alterations and increased gut permeability. Matrix-metalloprotease 9 (MMP-9) is capable of occludin degradation and disruption of the epithelial barrier, while increased PAR-2 promoter methylation was shown in patients with severe forms of the disease. Our aims were: 1. to examine the correlation of UC disease severity with fecal levels of MMP-9 and occludin mRNA and protein expression; 2. to examine PAR-2 and 4 mRNA expressions related to disease severity.

A comparison of physician-rated disease severity and patient reported outcomes in mild to moderately active ulcerative colitis

Background and aimsThe aim was to derive health state utility scores in ulcerative colitis (UC) by establishing the relationship between the physician-rated ulcerative colitis disease activity index (UCDAI) and a patient reported EQ-5D by statistically mapping the two instruments. MethodsIn a randomised controlled trial comparing oral plus enema mesalazine treatment with oral mesalazine treatment alone (PINCE), UCDAI and EQ-5D scores were collected in parallel from patients with active UC. From these data, multinomial logistic regression was used to estimate response probabilities to each of the five domains of the EQ-5D index from assessment of UC disease severity using original and abbreviated (no endoscopy) versions of the UCDAI. Predicted EQ-5D responses were converted by Monte Carlo simulation to the EQ-5D index for predicting health-related quality of life (HRQoL). The reliability of the algorithm was tested using UCDAI scores from a second mesalazine RCT (PODIUM). ResultsThe abbreviated-UCDAI showed comparable explanatory performance to the full UCDAI. For patients in remission, mean utility was 0.939, 0.944, and 0.940U for PINCEestimated, PINCEobserved, and PODIUM, respectively. Mild/moderate and relapsing cases showed mean utilities of 0.801, 0.811, and 0.775, respectively; whilst for those in severe relapse, the mean utilities were 0.630, 0.700 and 0.660units, respectively. The mean squared error between actual and predicted utilities from observations in PINCE was 0.019. ConclusionResponse mapping of UC activity to EQ-5D domains produced reliable estimates of patient-rated health state utility consistent with UCDAI rated severity. Comparing abbreviated-UCDAI and full UCDAI suggests that inclusion of endoscopy scores has limited predictive value in estimating patient HRQoL.

Can bedside criteria predict complications after Ileal Pouch-Anal Anastomosis for chronic Ulcerative Colitis?

Truelove and Witts' criteria remains the gold standard for assessment of disease severity in ulcerative colitis, but it's clinical use is not ideal given its reliance on the combination of clinical, laboratory, and radiographic variables. In a recent study reporting the feasibility of minimally invasive subtotal colectomy and ileal pouch-anal anastomosis (IPAA) for fulminant colitis, we described surgical selection criteria which can be assessed at the bedside, including 1) recent (prior 6 weeks) hospitalization, 2) recent transfusion, 3) malnutrition (weight loss, hypoalbuminemia, or need for parenteral nutrition), or 4) immunosuppression (corticosteroids or infliximab). We aimed to determine if these criteria were associated with overall or infectious complications when present in a cohort of patients who underwent 2-stage IPAA. We identified all adult patients with CUC who underwent hand-assisted laparoscopic total proctocolectomy TPC-IPAA (stage 1 of 2) at our institution from 2004 - 2009 using a prospectively maintained database. Disease extent and severity was assessed according to the Montreal classification. Univariate analysis was performed to assess associations with overall or infectious complications after IPAA. Multivariate logistic regression analysis was performed to assess associations with overall 30-day complications. Data are frequency (proportion), median (interquartile range). Over 5-years, 212 patients underwent HALS-IPAA. Overall age was 35 (26 - 46) years, 88 (41%) women, BMI 25.3 (21.3 - 28.4) kg/m2. According to the Montreal classification of extent, 172 (80%) had pancolitis (E3), 34 (16%) had left-sided colitis (E2), and 8 (3.7%) had ulcerative proctitis (E1), and severity was classified as follows: 7 (3.2%) had severe colitis (S3), 84 (39%) moderate colitis (S2), 100 (48%) mild colitis (S1), and 23 (11%) asymptomatic (S0). A total of 169 (79%) were receiving steroids or infliximab, 49 (23%) had been recently hospitalized, 27 (13%) had evidence of malnourishment, and 16 (7.4%) had recent transfusion. Median operative time was 290 (241 - 354) minutes, 16 (7.4%) were converted to laparotomy, and the median post-operative length of stay was 5 (4 - 7) days. Overall 81 (38%) of patients developed a complication of any grade; 29 of these (13.5% overall) were infectious complications. On univariate analysis, neither Montreal classification extent or severity, nor any of the 4 clinical criteria were associated with overall complications; recent hospitalization (p= 0.5), transfusions (p= 0.82), immunosuppression (p= 0.96) were not associated with infectious complications, while malnutrition was associated with post-operative infections (p= 0.04). When stratified by the number of selection criteria present (2 or more, 3 or more) no statistically significant associations were noted with either overall or infectious complications on univariate analysis. On multivariate analysis of predictors for overall complications, including adjustment for disease severity, no statistically significant associations were noted; multivariate analysis of infectious complications was limited by the absolute number of events. In patients undergoing 2-stage ileal pouch-anal anastomosis, malnutrition appears to be a risk factor for post-operative infectious complications. Further study in a larger cohort is needed to determine if this association is independent of disease severity, extent, or other clinically important variables.

Increased serum levels of L-arginine in ulcerative colitis and correlation with disease severity

L-arginine (L-Arg) is a semi-essential amino acid that is the substrate for both nitric oxide and polyamine synthesis. Cellular uptake of L-Arg is an active transport process that is subject to competitive inhibition by L-ornithine (L-Orn) and L-lysine (L-Lys). We investigated L-Arg utilization in patients with ulcerative colitis (UC). Serum was collected from 14 normal controls and 22 UC patients with pancolitis of moderate or severe activity by histopathology score. The Mayo Disease Activity Index (DAI) and endoscopy subscore were assessed. Serum amino acid levels were measured by high-performance liquid chromatography. Arginine availability index (AAI) was defined as [L-Arg]/([L-Orn] + [L-Lys]). Serum L-Arg levels were significantly associated with histopathologic grade (P = 0.001). L-Arg levels were increased in subjects with severe colitis when compared to those with moderate colitis or normal mucosa. L-Orn + L-Lys levels were also increased in severe colitis, so that AAI was not significantly increased. L-Arg levels were also strongly associated with the endoscopy subscore (P < 0.001). There was a strong correlation between DAI and L-Arg levels (r = 0.656, P < 0.001). Serum L-Arg levels correlate with UC disease severity but availability is not increased due to competitive inhibition by L-Orn and L-Lys. Our findings suggest that L-Arg uptake by cells in the inflamed colon is defective, which may contribute to the pathogenesis of UC. Studies delineating the mechanism of uptake inhibition could enhance our understanding of UC or lead to novel treatment options.

W1172 Serum Levels of L-Arginine Are Correlated with Disease Severity in Ulcerative Colitis

W1172 Serum Levels of L-Arginine Are Correlated with Disease Severity in Ulcerative Colitis

Mucosal vascular pattern in ulcerative colitis: observations using narrow band imaging colonoscopy with special reference to histologic inflammation

Narrow band imaging (NBI) is a novel endoscopy system, which enables a clear visualization of the mucosal vasculature of the gastrointestinal tract. The aim of this study is to determine whether this system may be of value for assessing the disease severity in ulcerative colitis (UC). We observed the mucosal vascular pattern (MVP) in 157 colorectal segments of 30 patients with UC using both conventional and NBI colonoscopy. The MVP was determined to be normal or distorted under conventional colonoscopy and, subsequently, to be clear or obscure under NBI colonoscopy. The histologic variables in each segment were assessed in biopsy specimen. The possible correlation between MVP and the histologic grade of inflammation was evaluated. The MVP under conventional colonoscopy was normal in 60 segments while it was distorted in 97 segments. In all of the former 60 segments, their MVP was clear under NBI colonoscopy. The MVP in the latter 97 segments were determined to be clear (n = 44) or obscure (n = 53) under NBI colonoscopy. Acute inflammatory cell infiltrates (26% vs. 0%, p = 0.0001), goblet cell depletion (32% vs. 5%, p = 0.0006), and basal plasmacytosis (2% vs. 21%, p = 0.006) were more frequently observed in segments with an obscure MVP than in those with a clear MVP. NBI colonoscopy may be of value for determining the grade of inflammation in patients with quiescent UC.

PG125 ESTABLISHING THE RELATIONSHIP BETWEENTHE ULCERATIVE COLITIS DISEASE ACTIVITY INSTRUMENT (UCDAI) AND PATIENT HEALTH RELATED QUALITY OF LIFE FROM A LARGE RANDOMISED CONTROLLED TRIAL

OBJECTIVES: The purpose of this study was to conduct a statistical mapping between standard assessments of disease severity in ulcerative colitis (UC) using the ulcerative colitis disease activity index (UCDAI) and a patient reported generic health-related utility instrument to estimate patient preference-based health utility. METHODS: Multinomial logistic regression was used to estimate response probabilities to each of the five domains of the EuroQol-5D index instrument (EQ-5D) from assessments of UC severity using the original UCDAI and an abbreviated (ie. No endoscopy) UCDAI instrument in patients enrolled into a clinical trial studying the use of oral/rectal mesalazine combination maintenance therapy. Predicted EQ-5D health utility was estimated by Monte Carlo bootstrap simulation. The predictive ability of the response mapping was assessed by comparing estimated and directly measured utility derived from the UK tariff (Dolan, 1997). RESULTS: Evaluable datawere available for 128 patients,59%of whom were male, and for which the median age at screening was 43.5 years (IQR 30 to 54). Using UCDAI item responses as predictor variables, the percentage of variance in domain response attributable to predictor variable change ranged from 20.4% (ANXIETY/DEPRESSION) to 42.5.5% (SELF CARE). Summary UCDAI score was a less effective predictor of the same domains (R2 = 13.2% and 20.4 respectively). Items from the abbreviated UCDAI (no endoscopy score) showed comparable explanatory performance (R2 range 21.3% to 38.0%). The mean utility predicted by the UCDAI item algorithm was 0.844 (sd 0.104) and 0.852 (sd 0.175) by estimation directly from EQ-5D responses (p = 0.238). The mean squared error (MSE) between the actual and predicted utilities was 0.019. Predicted EQ-5D utility was within 3% of the actual utility in 38.1% of cases and within 10% of the actual utility in 58.5% of cases. CONCLUSIONS: In this study responsemapping of UC disease activity to EQ-5D domains produced reliable estimates of preference-based health-related utility. The near-identical explanatory power of models using either the original or abbreviated UCDAI assessment suggests that endoscopy adds little information to patient perception of UC disease severity. The results from this study will enable future investigators to generate health-related utility from the UCDAI in trials where this data was not prospectively collected

Histologic Predictors of Future Ulcerative Colitis Disease Severity

Purpose: Accurate prediction of future disease severity course may optimize management of ulcerative colitis (UC) including tailoring “top-down” versus “step-up” approaches to therapy. We sought to determine if specific histologic variable could predict future clinical UC disease severity. Methods: The initial histopathology parameters from 19 patients with UC that later (≥ 6 months) underwent colectomy for severe disease (colectomy/severe course group) were compared to those from 25 patients who did not require colectomy (no colectomy/mild course group) from 1998–2007. The pathology variables assessed were cryptitis, cryptopenia, crypt branching, crypt abscesses, ulcerations and mucin depletion. The predictive value of disease extent, endoscopic severity, and initial serum albumin were also assessed. Groups were compared using Chi-square, Mann-Whitney or t-test with a significance level of 0.05. Patients with dysplasia were excluded. Results: Patients were followed for a median of 3 years. Median age was 39 years in no colectomy group versus 34 years in colectomy group (NS). Severe cryptitis occurred in 16/19 (84%) in colectomy group versus 13/25 (52%) in no colectomy group (P= 0.026). Cryptopenia was present in 11 (58%) colectomy group versus 10 (40%) no colectomy group (P= 0.239). In colectomy group, crypt abscesses were present in 16 (84%), crypt branching 16 (84%), mucin depletion 18 (96%), ulceration 6 (24%) at the initial histopathology. The prevalence of crypt abscess, crypt branching, cryptopenia, mucin depletion, ulceration were all not significantly different in the colectomy (severe course) versus no colectomy (mild course) group. A Mayo Score ≥2 on initial endoscopy was not significantly more common in colectomy group 13 (69%) versus no colectomy group 18 (75%) (P= 0.228). The initial albumin was significantly lower in the colectomy group 2.9 g/dL (SD ± 0.88) versus noncolectomy group 3.5 g/dL (SD ± 0.57) (P= 0.040). Pancolitis at initial endoscopy was not more prevalent in the colectomy group (32%) versus noncolectomy (32%). Immunosuppressant usage was not statistically different between groups: colectomy group (24%) versus no colectomy (32%). Conclusion: Cryptopenia, mucin depletion, crypt branching and crypt abscesses are common findings in UC but do not predict future clinical disease severity. The initial serum albumin and cryptitis were the only variables predictive of future progression to colectomy. Histopathology with extensive cryptitis was more predictive of future severe disease that eventually required colectomy than was the initial endoscopic severity or disease extent. Future prospective studies are required to confirm the prognostic value of diffuse cryptitis to predict a future colectomy in UC.

Racial Differences in Disease Extent and Severity in Patients with Ulcerative Colitis: A Retrospective Cohort Study

Ulcerative colitis (UC) is increasing in African-Americans (AA). The objectives of this study were to assess disease extent and severity in UC by race. Disease extent and severity was assessed in UC outpatients evaluated at the University of Maryland and Baltimore VA from 1997 to 2005. About 197 patients were identified; 47 were AA (23%). Of AA, 23% had proctitis, 23% had left-sided colitis, and 53% had extensive colitis compared to 10%, 31%, and 59% of Caucasians, respectively (P = 0.056). African-Americans were less likely to ever receive steroids (45% versus 62%; P = 0.065), be treated with > or = 2 courses of steroids (54% versus 68%; P = 0.242) or be steroid dependant (33% versus 46%; P = 0.304). After adjustment, only female gender (OR 0.32, [0.16-0.66]) and age at diagnosis (OR 2.50, [1.28-4.90]) were associated with extensive colitis. Being seen at UMMS (OR 5.10, [2.60-10.10]) was associated with steroid use. Race was not associated with extent of colitis or disease severity in UC.

Younger Age at Diagnosis Predicts Disease Severity in Ulcerative Colitis

Purpose: Canada has one of the highest incidences of ulcerative colitis (UC) in the world, with 3500 new cases each year and a prevalence of over 60, 000†. Previous studies have examined the natural history of UC, however, this is the first to examine it in Southwestern Ontario (SWO). London is uniquely situated with a catchment area of nearly all of SWO, and the London Health Sciences Centre – South Street Hospital (LHSC-SSH) Inflammatory Bowel Disease (IBD) clinic is set up to longitudinally follow patients who are diagnosed and treated there. The goal of the current study is to understand the demographic characteristics of this population in order to predict disease severity. †Am J Gastro 2006;101:1559–68. Methods: Records from 1996 to 2001 were examined to create a database of UC patients seen in the LHSC-SSH IBD clinic. To be included, patients’ charts were required to have information of their disease presentation and a minimum of five years of follow-up. Charts were reviewed using standardized data collection forms. Disease severity was generated during the chart review process, and non-endoscopic Mayo Severity Index‡ criteria were collected into a composite. ‡NEJM 1987;317:1625–9. Results: 102 consecutive patients’ data were entered into the database. Demographic analyses revealed that 51% of the patients were male, the mean age at diagnosis was 39 years, 13.7% had a first degree relative with IBD, 61.8% were nonsmokers and 24.5% were ex-smokers. In 22.5% of patients the disease was limited to proctitis, 21.6% had proctosigmoiditis, 22.5% had left-sided colitis, and 32.4% had pancolitis. Standard multiple regression analysis which regressed a composite of physician global assessment of disease severity, average number of bowel movements, and average amount of blood in bowel movements on year of diagnosis and age at time of diagnosis was significant, R2 = .306, F (7, 74) = 4.66, P < .01. Delay from symptoms to diagnosis of UC, gender, family history of IBD, smoking status and disease severity at the time of diagnosis did not significantly predict the composite measure. Conclusion: A composite of UC disease severity, blood in bowel movements, and number of bowel movements is associated with younger age at diagnosis as well as year of diagnosis in a longitudinal cohort of UC patients in SWO. This suggests a potential mechanism for predicting disease severity at diagnosis and may be a step towards the identification of prognostic indicators of UC.

Laboratory Values for Children With Newly Diagnosed Inflammatory Bowel Disease

The goal was to determine how often common laboratory tests yield normal results at the time of diagnosis for children with inflammatory bowel disease. Data were obtained from a registry of children with newly diagnosed inflammatory bowel disease who were enrolled prospectively in 18 US/Canadian centers. Laboratory values investigated included hemoglobin level, platelet count, albumin level, and erythrocyte sedimentation rate. Disease severity was categorized by physician global assessment. A total of 526 children (mean age: 11.6 years; 58% male; 392 with Crohn disease and 134 with ulcerative colitis) were studied. All 4 values were normal for 21% of patients with mild Crohn disease and 54% with mild ulcerative colitis. In contrast, only 3.8% of children with moderate/severe Crohn disease and 4.3% with moderate/severe ulcerative colitis had normal results for all 4 tests. The erythrocyte sedimentation rate was least likely to be normal; overall, 26% of patients with inflammatory bowel disease had a normal erythrocyte sedimentation rate, including 18% with moderate/severe disease. Hemoglobin levels were normal for 32%, platelet counts for 50%, and albumin levels for 60%. There was no clear association between Crohn disease location and either severity or number of normal laboratory values. In contrast, there were direct correlations between ulcerative colitis disease severity and both the extent of bowel inflammation and the number of abnormal laboratory tests. The presence of normal screening laboratory studies should not dissuade clinicians from considering a diagnosis of inflammatory bowel disease.

Alterations in the Composition of the Supramucosal Defense Barrier in Relation to Disease Severity of Ulcerative Colitis

Mucin glycoproteins and trefoil peptides play an important role in protection and repair of the gastrointestinal epithelium. This study investigates alterations in mucin and trefoil peptide gene expression and product localization in ulcerative colitis (UC). Product localization and message expression of mucin MUC1 to 6 and trefoil peptide TFF1 to 3 genes was analyzed in rectosigmoid tissue from a cohort of patients with active UC and compared with that of normal colorectal mucosa. MUC1 expression was upregulated in severe UC at the site of rupture of crypt abscesses. Reduction in MUC2 expression occurred in UC adjacent to ulceration. No alteration in MUC3 or MUC4 gene expression was detectable in UC compared with normal colorectal mucosa. No ectopic expression of MUC5AC, MUC5B, or MUC6 was identified in UC. Ectopic TFF1 expression was identified in tissues eliciting histological features of severe disease. Decreased TFF3 localization was demonstrated in UC tissues, but no TFF2 expression was detected in any colorectal specimens. Subtle alterations in composition of the supramucosal defense barrier exist in UC and vary in relation to clinical severity of disease. There is upregulation in mucin MUC1 at crypt abscesses and neo-expression of TFF1 trefoil peptide in severe disease.

DNA flow cytometric evaluation of cell cycle distribution in ulcerative colitis: a proposed method for assessing severity of disease.

The assessment of disease severity in ulcerative colitis depends mainly on subjective variables, and an objective method of assessing mucosal inflammation is needed. Determination of the synthetic phase of the cell cycle is an accurate expression of inflammatory activity in the colonic mucosa. The aim of the study was to find out if the proliferative index or the synthetic phase (S phase) of the colonic mucosa of patients with ulcerative colitis, as evaluated by DNA flow cytometry, is a reliable and reproducible marker of disease activity. Sixty consecutive patients with ulcerative colitis of different degrees of activity were entered into the study and submitted to colonoscopy plus multiple rectal biopsies. Disease severity was defined for each patient by means of a clinical, endoscopic, and histological score. Flow cytometry was used to calculate the proliferative index and the S phase of the cell cycle. A statistically significant correlation (p < 0.001) was found between all indices of severity. It is suggested that flow cytometric evaluation of the cell cycle in the rectal mucosa may be an efficient method of assessing severity of disease and efficacy of medical treatment in ulcerative colitis.

Potential of measurements of unsaturated vitamin B12-binding capacity in serial colonoscopic biopsy specimens for global and regional assessments of disease severity in inflammatory bowel disease.

We investigated whether measurements of unsaturated vitamin B12-binding capacity (UBBC), in homogenates of serial colonoscopic biopsy specimens, could be used as objective measures of disease severity in ulcerative colitis (UC) and Crohn's disease (CD). On a regional basis UBBC activity correlated with and showed good agreement with endoscopic and histologic activity scores (r = 0.8 and 0.6, respectively, for UC, and r = 0.7 and 0.7, respectively, for CD). For global assessment aggregate UBBC, endoscopic and histologic scores were compared with standard clinical activity scores. In UC, correlations with the van Hees index were r = 0.7, 0.8, and 0.7, respectively, and UBBC assays accurately reflected both regional and global disease activity. In CD, correlations with the CDAI were -0.1, 0.7, and 0.6, respectively. Thus, aggregate UBBC scores failed to reflect disease activity in CD, in which focal deep ulcers may produce high symptom scores but in which adjacent specimens may show no acute inflammation.

Assessment profiles of disease severity in ulcerative colitis.

There is no general agreement as to which activity profile or activity is preferable for the clinical assessment of ulcerative colitis. Examples of qualitative and quantitative indices are given. Most of the latter include clinical data, macroscopic evaluation at endoscopy and histological grading of inflammation. It is proposed that the activity of the disease, reflected by the patient's symptoms, might be the determinant of the treatment, and the severity of the disease, defined by objective means, could be assessed in scientific evaluation.