Disease Severity In Ulcerative Colitis Research Articles

Extraintestinal manifestation of inflammatory bowel disease and associated factors in pediatric patients

ObjectiveExtraintestinal manifestations in irritable bowel disease (IBD), Crohn's disease and ulcerative colitis are reported in different system of the body. We aimed to investigate the factors determining disease severity and evaluate extraintestinal manifestations in patients with irritable bowel disease based on disease activity scoring system. MethodsThis cross-sectional study was conducted on all patients with irritable bowel disease referred to clinic and gastroenterology ward of (XXX). Medical history, gastrointestinal complications and incidence of extraintestinal manifestations were recorded. Disease severity in ulcerative colitis was rated based on PUCAI (Pediatric Ulcerative Colitis Activity Index) score and in Crohn's disease was calculated based on PCDAI (Pediatric Crohn's Disease Activity Index) score. ResultsOf 73 children included in our study, 54.80% were diagnosed with ulcerative colitis and 45.20% were diagnosed with Crohn's disease. The most prevalent symptom was weight loss (81.81%), diarrhea (72.72%) and abdominal pain (69.69%) in Crohn's diseases and bloody diarrhea (80%), abdominal pain (77.5%) and weight loss (57.5%) in ulcerative colitis. The average of PCDAI score was 43.44 and PUCAI score was 35.62. The most prevalent extraintestinal manifestation of the disease was arthritis in 7 Crohn's disease patients (21.21%) and 5 patients (12.5%) with ulcerative colitis, oral plague in 5 patients (15.15%) with Crohn's disease and erythema nodosum in 2 patients (6.06%) with Crohn's disease. ConclusionThe severity of oral plaque was positively associated with the severity of the disease. There was no significant association among other parameters. Scoring systems, to determine the extraintestinal manifestation, should be standardized based on the scoring outcomes.

Anti-proteinase 3 antineutrophil cytoplasmic antibody reflects disease activity and predicts the response to steroid therapy in ulcerative colitis

BackgroundSerum anti-proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA) is a disease-specific antibody against granulomatosis with polyangiitis. PR3-ANCA is a useful serological marker for disease severity in ulcerative colitis (UC). The purpose of this study was to investigate whether PR3-ANCA levels could also predict the success of induction therapy and to compare its performance against other markers, including serum CRP and fecal hemoglobin.MethodsThis was a multicenter retrospective study. In total, 159 patients with active-phase UC underwent colonoscopy. Disease activity was measured using the Mayo endoscopic subscore (MES). PR3-ANCA positivity and the response to induction therapy, either 5-aminosalicylic acid or steroid, were assessed. PR3-ANCA, CRP, and fecal hemoglobin were measured during the active phase, and during clinical remission.ResultsEighty-five (53.5%) of 159 patients with active UC were positive for PR3-ANCA. PR3-ANCA titers were significantly higher in the group of patients with MES 3 compared to patients with MES 1 (P = 0.002) or MES 2 (P = 0.035). Steroid therapy was administered to 56 patients with a median partial Mayo score of 7 (5–9), which is equivalent to moderate-to-severe disease activity. PR3-ANCA positivity of non-responders to steroid therapy was significantly higher than that of responders (71.9% vs, 41.7%, P = 0.030), whereas CRP and fecal hemoglobin were not predictive of steroid response. Multivariate analysis demonstrated that PR3-ANCA positivity was associated with non-response to steroid therapy (odds ratio 5.19; 95% confidence interval, 1.54–17.5; P = 0.008). Of the 37 patients treated to clinical remission who were also positive for PR3-ANCA during the active phase, 27 had an MES of ≥ 1, and 10 patients had an MES of 0. In clinical remission, the proportion of patients with MES 0 in 17 patients whose PR3-ANCA became negative was significantly higher than that in 20 patients whose PR3-ANCA remained positive (47.1% vs. 10.0%, P = 0.023).ConclusionsPR3-ANCA not only serves as a marker of disease activity, but also predicts the failure of steroid therapy in moderate-to-severe UC.Trial registration: This study was retrospectively registered in the UMIN Clinical Trials Registry System (000039174) on January 16, 2020.

Profile of patients with inflammatory bowel disease in conjunction with unmet needs and decision-making for choosing a new biologic therapy: a baseline analysis of the VEDOIBD-Study.

We characterized the profile of Crohn's disease (CD) or ulcerative colitis (UC) biologic-naïve patients (starting a new therapy with vedolizumab or TNFα-antagonists), their baseline disease activity predictors, and their perception of the quality of life (HRQoL). The VEDOIBD-Study is a real-world study on the effectiveness of vedolizumab vs other biologics as induction and maintenance therapy for CD and UC. A total of 627 CD and 546 UC patients were enrolled from IBD-experienced centers across Germany. In both biologic-naïve vedolizumab (n=397) and anti-TNF (n=359) patients, CD and UC disease severity and HRQoL predictors were analyzed with logistic regression. The results were reported as odds ratio (OR) and 95% confidence interval (CI). When compared to biologic-naïve anti-TNF patients, a first biological therapy with vedolizumab was considered for older CD patients, with a less complicated though longer disease course, and with a history of comorbidities. No differences in (unmet) needs were observed among patients with UC. The presence of extra-intestinal manifestations in biologic-naïve anti-TNF patients with CD (OR (95% CI): 3.83 (1.69-8.68)) and, in both biologic-naïve groups of patients with UC, stool frequency (2.00 (1.25-3.19); 1.82 (1.10-3.02), respectively) and rectal bleeding (2.24 (1.20-4.18); 1.92 (1.19-3.11), respectively) emerged as the most important predictors of disease severity, which in turn were also significantly associated with a worse HRQoL. This study highlights the existence of unmet medical needs of patients with CD or UC, for whom a new biological therapy is planned as part of the VEDOIBD-Study, which considerably impacts their HRQoL.

Colonic Epithelial-Derived Selenoprotein P Is the Source for Antioxidant-Mediated Protection in Colitis-Associated Cancer

Patients with inflammatory bowel disease (IBD) demonstrate nutritional selenium deficiencies and are at greater risk of developing colon cancer. Previously, we determined that global reduction of the secreted antioxidant selenium-containing protein, selenoprotein P (SELENOP), substantially increased tumor development in an experimental colitis-associated cancer (CAC) model. We next sought to delineate tissue-specific contributions of SELENOP to intestinal inflammatory carcinogenesis and define clinical context. Selenop floxed mice crossed with Cre driver lines to delete Selenop from the liver, myeloid lineages, or intestinal epithelium were placed on an azoxymethane/dextran sodium sulfate experimental CAC protocol. SELENOP loss was assessed in human ulcerative colitis (UC) organoids, and expression was queried in human and adult UC samples. Although large sources of SELENOP, both liver- and myeloid-specific Selenop deletion failed to modify azoxymethane/dextran sodium sulfate-mediated tumorigenesis. Instead, epithelial-specific deletion increased CAC tumorigenesis, likely due to elevated oxidative stress with a resulting increase in genomic instability and augmented tumor initiation. SELENOP was down-regulated in UC colon biopsies and levels were inversely correlated with endoscopic disease severity and tissue S100A8 (calprotectin) gene expression. Although global selenium status is typically assessed by measuring liver-derived plasma SELENOP levels, our results indicate that the peripheral SELENOP pool is dispensable for CAC. Colonic epithelial SELENOP is the main contributor to local antioxidant capabilities. Thus, colonic SELENOP is the most informative means to assess selenium levels and activity in IBD patients and may serve as a novel biomarker for UC disease severity and identify patients most predisposed to CAC development.

S0692 Characterizing Prior Healthcare Resource Utilization by Disease Severity in Ulcerative Colitis: Real World Data From the Corrona Inflammatory Bowel Disease Registry

INTRODUCTION: Ulcerative colitis (UC) is a chronic, life-long inflammatory disease of the colon that poses a substantial burden for more than 1 million patients in the USA. This study aimed to characterize whether higher disease severity is associated with a history of greater healthcare resource utilization (HCRU) in UC. METHODS: Data were collected at enrollment for patients aged ≥18 years with a physician diagnosis of UC in the Corrona Inflammatory Bowel Disease Registry between 2017 and 2020. Exclusion criteria included indeterminate colitis (n = 30), change in diagnosis after enrollment (n = 21), or missing disease severity (n = 38) or history of HCRU measures at the time of enrollment (n = 12). Patients were stratified by disease severity (remission [0–1], mild [2–4], or moderate/severe [≥5]; partial Mayo Clinic Score), and associations between disease severity and history of HCRU were evaluated. The Cochran-Armitage test for trend was used for binary variables, and the Jonckheere-Terpstra test was used for continuous and interval/ordinal variables. RESULTS: 839 patients with UC met inclusion criteria (mean age 47.3; 54.7% female) (Table 1). Greater disease severity was associated with more prevalent usage (Table 2) of biologics (39.3%, 52.9%, 59.8%; remission, mild, moderate/severe, respectively; P < 0.001) and corticosteroids (8.9%, 20.2%, 32.1%; P < 0.001), but fewer with 5-aminosalicyclic acid (54.5%, 48.1%, 42.0%; P = 0.010). Significant associations and increasing trends were observed between disease severity and history of inflammatory bowel disease (IBD)-related hospitalizations in the past 12 months (10.8%, 16.3%, 33.0%; P < 0.001), number of IBD-related hospitalizations (0.1, 0.3, 0.5; P = 0.001), history of emergency room (ER) visits (13.5%, 19.4%, 34.5%; P < 0.001), and number of ER visits in the past 12 months (0.2, 0.4, 0.5; P = 0.002) (Table 3). CONCLUSION: Our study demonstrates that in real-world patients with UC, there was a significant trend of greater disease severity with higher recent HCRU use. Although there was higher current utilization of biologics and corticosteroids with worsening disease severity, the temporality and effect of these treatments is unclear. Additional longitudinal analyses are needed to determine if reduction in disease severity results in diminished future HCRU.Table 1Table 2Table 3

S0691 Worsening Patient-Reported Outcomes With Increasing Disease Severity in Ulcerative Colitis in the USA: The National Health and Wellness Survey

INTRODUCTION: Ulcerative colitis (UC) is a debilitating disease that leads to poor patient well-being. We aimed to establish the relationship between self-reported UC severity and patient-reported outcomes (PROs). METHODS: Data from the 2019 US National Health and Wellness Survey (NHWS)—a self-administered, internet-based survey that is representative of the US adult population in terms of age, sex, and race/ethnicity (N = 74,895)—were used. Patients with UC were defined by self-reported UC diagnosis. Respondents were categorized by self-reported UC severity: mild (n = 464), moderate/severe (n = 233), and non-UC controls (NUC) (n = 74,198). Patient-reported outcomes (PROs) were measured by SF-36v2, SF-6D, EQ-5D Visual Analogue Scale (VAS), and Work Productivity and Activity Impairment (WPAI). Bivariate analyses were conducted to evaluate differences between UC groups (mild vs moderate/severe vs NUC). Categorical variables were analyzed using chi-square tests; continuous variables by analysis of variance. Two-tailed P values < 0.05 were considered statistically significant. RESULTS: Mean age (Table 1) differed significantly between groups (NUC = 47.6 ± 17.3, mild = 51.4 ± 16.9; moderate/severe = 43.8 ± 14.8; P < 0.001), whereas sex did not (NUC = 43.1% male, mild = 40.5%; moderate/severe = 45.5%; P = 0.0405). Mean SF36v2 scores (Table 2) significantly decreased with disease presence and severity for both mental (NUC = 46.6 ± 11.8, mild = 44.7 ± 12.4, moderate/severe = 38.2 ± 11.4; P < 0.001) and physical (NUC = 50.3 ± 9.5, mild = 45.8 ± 10.1, moderate/severe = 40.7 ± 10.4; P < 0.001) components. Similar trends were observed for mean SF-6D (NUC = 0.72 ± 0.14, mild = 0.67 ± 0.15, moderate/severe = 0.57 ± 0.14; P < 0.001), and EQ-5D VAS (NUC = 75.5 ± 22.5, mild = 68.5 ± 24.98, moderate/severe = 61.1 ± 28.1; P < 0.001). WPAI outcomes were poorer with increasing disease severity, including absenteeism (NUC = 8.5 ± 19.6%, mild = 16.6 ± 25.2%, moderate/severe = 28.2 ± 26.6%; P < 0.001), presenteeism (NUC = 21.5 ± 29.3%, mild = 34.7 ± 34.9%, moderate/severe = 58.9 ± 31.8%; P < 0.001), and overall work impairment (NUC = 24.2 ± 31.7%, mild = 38.4 ± 37.3%, moderate/severe = 65.3 ± 33.6%; P < 0.001). UC symptoms (Table 3) were more prevalent and frequent in the moderate/severe group (P < 0.05). CONCLUSION: PROs worsened with UC disease severity. Patients with moderate/severe UC demonstrated significantly worse absenteeism, presenteeism, and lower scores on the SF-36v2, EQ-5D, and SF-6D than those with mild UC or without UC. Appropriate management of UC may reduce disease severity and potentially improve outcomes and PROs.Table 1Table 2Table 3

S3186 Healthcare Resource Utilization Increases With Disease Severity in Ulcerative Colitis in the USA: The National Health and Wellness Survey

S3186 Healthcare Resource Utilization Increases With Disease Severity in Ulcerative Colitis in the USA: The National Health and Wellness Survey

P121 REAL WORLD PREVALENCE OF BOWEL MOVEMENT URGENCY – A SNAPSHOT OF SYMPTOM EXPERIENCE REPORTED BY PATIENTS WITH ULCERATIVE COLITIS PARTICIPATING IN SPARC IBD

Abstract Background Urgency, also referred to as bowel movement urgency or bowel urgency, is the sudden need for a bowel movement. Bowel urgency is one of the most bothersome and important symptoms experienced by patients with ulcerative colitis (UC), contributing to decrements in quality of life. Bowel urgency is distinct from the common symptoms associated with UC, namely stool frequency and rectal bleeding, however patients often experience all symptoms, urgent, frequent bowel movements with bleeding, concurrently. Bowel movement urgency is a key symptom for triggering clinical consideration of UC diagnosis and for defining more severe disease activity in clinical practice. Methods The results published here are based on data obtained from the IBD Plexus program of the Crohn’s &amp; Colitis Foundation. To better understand the prevalence of bowel movement urgency in patients with UC, an ad hoc analysis was performed using data from a Study of a Prospective Adult Research Cohort with IBD (SPARC IBD), a multicenter longitudinal study of adult patients with IBD that collects and links clinical data, patient-reported outcome (PRO) data, and serial bio-samples throughout the course of the patients’ disease. The enrollment visit was defined as 7 days from the patients’ date of enrollment in SPARC IBD. At study enrollment, patients were asked to answer questions based on their symptom experiences. Patients reported how much urgency they experienced before bowel movements on average during the past 3 days (none, mild, moderate, moderately severe, severe, not applicable). Descriptive analyses for patient demographic and disease characteristics were conducted. Additionally, contingency table analyses were conducted exploring the association of urgency with other UC symptoms and other measures of UC disease severity. Results Of 1,833 patients included in the SPARC IBD data cutoff of May 13, 2019 (Enrolled from 08 November 2016 to 15 May 2019), 582 were patients with UC, of which 514 had urgency data available. Overall, 51.8% of patients were male, and the mean age is 42.4 years (Table 1). At enrollment, 59.7% of patients reported some level (mild, moderate, moderately severe/severe) of urgency. Forty-six percent of UC patients with urgency data were receiving biologic treatment with 31% still reporting mild urgency, and 32% reporting moderate to severe urgency (Table 1). The severity of urgency was associated with patient reported severity of other UC symptoms and disease activity (Table 2). Conclusion Results from ad hoc analyses using a real-world sample of patients with UC suggest that bowel movement urgency is a prevalent symptom of UC which varies with disease activity.

P595 Feasibility and performance of a fully automated endoscopic disease severity grading tool for ulcerative colitis using unaltered multisite videos

Abstract Background Endoscopic assessment is a core component of disease severity in ulcerative colitis (UC), but subjectivity threatens accuracy and reproducibility. We aimed to develop and test a fully-automated video analysis system for endoscopic disease severity in UC. Methods A developmental dataset of local high-resolution UC colonoscopy videos were generated with Mayo endoscopic scores (MES) provided by experienced local reviewers. Videos were converted into still images stacks and annotated for both sufficient image quality for scoring (informativeness) and MES grade (e.g. Mayo 0,1,2,3). Convolutional neural networks (CNNs) were used to train models to predict still image informativeness and disease severity grading with 5-fold cross-validation. Whole video MES models were developed by matching reviewer MES scores with the proportion of still image predicted scores within each video using a template matching grid search. The automated whole video MES workflow was tested in a separate endoscopic video set from an international multicenter UC clinical trial (LYC-30937-EC). Cohen’s kappa coefficient with quadratic weighting was used for agreement assessment. Results The developmental set included 51 high-resolution videos (Mayo 2,3 41.2%), with the multicenter clinical trial containing 264 videos (Mayo 2,3 83.7%, p &amp;lt; .0001) from 157 subjects. In 34,810 frames, the still image informative classifier had excellent performance with an AUC of 0.961, sensitivity of 0.902, and specificity of 0.870. In high-resolution videos, agreement between reviewers and fully-automated MES was very good with correct prediction of exact MES in 78% (40/51,κ=0.84, 95% CI 0.75–0.92) of videos (Figure 1). In external clinical trial videos where dual central review was performed, reviewers agreed on exact MES in 82.8% (140/169) of videos (κ = 0.78, 95% CI 0.71–0.86). Automated MES grading of the clinical trial videos (often low resolution) correctly distinguished Mayo 0,1 vs. 2,3 in 83.7% (221/264) of videos. Agreement between automated and central reviewer on exact MES occurred in 57.1% of videos (κ=0.59, 95% CI 0.46–0.71), but improved to 69.5% when accounting for human reviewer disagreement. Automated MES was within 1-level of central scores in 93.5% of videos (247/264). Ordinal characteristics are shown for the automated process, predicting progressively increasing disease severity. TPR, true positive rate; FPR, false-positive rate. Conclusion Though premature for immediate deployment, these early results support the feasibility for artificial intelligence to approach expert-level endoscopic disease grading in UC.

Colonic mucosa-associated candida assessed by biopsy culture is associated with disease severity in ulcerative colitis: A prospective study.

To evaluate the relationship of mucosa-associated candida (MAC) and disease severity in patients with ulcerative colitis (UC). We prospectively investigated the presence, nature, and quantification of MAC in patients with UC and its relationship with disease severity. Consecutive patients with UC were assessed for clinical, endoscopic, histological features and serum markers of disease severity. All patients underwent mucosal brushing cytology, brushing culture, and biopsy culture for candida growth. MAC was considered present if mucosal biopsy culture grew candida. Candida spp. identification was performed by matrix-assisted laser desorption/ionization. Serum β-D-glucan was measured with a Fungitell assay. Patients with irritable bowel syndrome who had undergone similar investigations were included as controls. Ninety-six patients with UC showed evidence of MAC more often than the controls (n = 20) based on biopsy culture (33.3% vs 5.0%, P = 0.011), brush cytology (30.2% vs 5.0%, P = 0.019), and brush culture (36.5% vs 10.0%, P = 0.021). Patients with UC had higher candida colony counts (≥103 CFU/mL) than controls (34.4% vs 5.0%, P = 0.007). Median β-D-glucan values were higher in patients with UC than in controls (103.26 pg/mL vs 66.51 pg/mL, P = 0.011). The UC group with MAC had a higher median total Mayo score, C-reactive protein, fecal calprotectin, β-D-glucan, and histological activity than those without MAC. Patients with UC more often show evidence of MAC and a higher candida colony count than controls. The presence of MAC is associated with high disease severity in patients with UC.

Effect of Lactocare® Synbiotic on Disease Severity in Ulcerative Colitis: A Randomized Placebo-Controlled Double-Blind Clinical Trial.

BACKGROUND Inflammatory bowel diseases are managed by different methods, which may not be well tolerated because of their side effects. Recently, pro-prebiotics are considered as a supplementary treatment in gastrointestinal diseases. In this study, the effect of Lactocare® (ZistTakhmir Company) was investigated on the disease severity in mild to moderate ulcerative colitis. METHODS In this randomized, double-blind clinical trial (Iranian Registry of Clinical Trials number: IRCT201407271264N5), 60 patients with mild to moderate ulcerative colitis were included. An 8-week trial was carried out comparing Lactocare® as a supplement with standard therapy against placebo. Simple Clinical Colitis Activity Index (SCCAI) was measured at baseline and after 8 weeks. Statistical analysis was performed using paired ttest to assess the temporal changes (before and after the treatment) in the mean of SCCAI in each group. Chi-square test was used to compare the response rates. Odds ratios (OR) and the 95% confidence intervals (95%CI) were also calculated. p values of less than 0.05 were considered significant. RESULTS A significant decreased mean SCCAI was seen in the intervention group (4.56 ± 2.56) vs. placebo group (6.54 ± 2.47) (p < 0.05). Response to treatment was seen in 64.3% of the treatment group vs. 47% in the placebo group (p = 0.18). Response to treatment was observed in 90.9% of patients with ulcerative colitis for more than 5 years compared with 44.4% of the control group (p = 0.01). CONCLUSION Regarding the effectiveness of pre-probiotics in mitigating symptoms in patients with ulcerative colitis, it could be suggested to try pre-probiotics in the standard treatment particularly in those with more than five years ofthe disease.

PGI50 THE RELATIONSHIP BETWEEN DISEASE SEVERITY AND HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH ULCERATIVE COLITIS IN JAPAN

Patients with ulcerative colitis (UC) experience abdominal pain and bloody diarrhea during the active phase of their disease, and their health-related quality of life (HRQOL) is often disrupted. Understanding patient's HRQOL along with disease severity is an important guide to select their treatment options for both patients and physicians. The aim of this study is to assess the relationship between disease severity and HRQOL in patients with UC in Japan. We conducted a multi-center, cross-sectional study in patients with UC. Patients with a variety of disease severity were recruited during their routine visits. Patients' disease severities were evaluated by their physicians using the Partial Mayo Score (pMayo). Patients were requested to fill in the Inflammatory Bowel Disease Questionnaire (IBDQ), EQ-5D, and the Work Productivity and Activity Impairment (WPAI), to assess their HRQOL and impairment in their daily work and activity. A total of 319 out-patients were enrolled from 12 health facilities. The mean age was 46 years old and 54% of patients were male. Of these, 60% of patients were in remission, 23% had a mild disease, and 18% had a moderate-to-severe disease based on the pMayo. The mean IBDQ scores were 190.5, 165.8 and 149.7 in remission, mild, and moderate-to-severe disease, respectively and these scores were statistically significant (P<0.001). The mean EQ-5D scores were also significantly lower in patients with moderate-to-severe symptoms than those in remission (mean=0.93, 0.86 and 0.79 in remission, mild and moderate-to-severe, respectively, p<0.001). A similar finding was observed with WPAI scores, where patients with moderate-to-severe disease symptoms had the largest impairment in both work and daily activity. The study demonstrated that UC disease severity is associated with patients' HRQOL. The more severe a level of disease the patients had, the greater impairment in HRQOL and work productivity patients experienced.

Characterization of Stool Virome in Children Newly Diagnosed With Moderate to Severe Ulcerative Colitis.

BackgroundViral infections have been suggested as possible triggers for the onset of ulcerative colitis (UC).MethodsWe employed VirCapSeq-Vert, a high-throughput sequencing virus capture platform, to examine the stool virome of children with newly diagnosed moderate to severe UC. We surveyed fecal samples collected at presentation, after symptom remission, and from a control group diagnosed with irritable bowel syndrome.ResultsSeventy subjects with UC (mean age 13 years, 45 had moderate symptoms, 25 had severe, 69 of 70 had a Mayo endoscopy subscore 2/3) were studied. We detected a wide range of animal viruses that were taxonomically classified into 12 viral families. A virus was present in 50% of fecal samples collected at presentation, 41% of samples collected after remission, and 40% of samples in our control group. The most frequently identified viruses were diet-based gyroviruses. The UC cohort had a significantly higher prevalence of anelloviruses compared with the control cohort. However, we did not identify a single virus that can be implicated in the onset of UC and did not find an association between UC disease severity and viral presence.ConclusionPresence of virus in stool was not associated with the onset of pediatric UC.

Performance of a Deep Learning Model vs Human Reviewers in Grading Endoscopic Disease Severity of Patients With Ulcerative Colitis

Assessing endoscopic disease severity in ulcerative colitis (UC) is a key element in determining therapeutic response, but its use in clinical practice is limited by the requirement for experienced human reviewers. To determine whether deep learning models can grade the endoscopic severity of UC as well as experienced human reviewers. In this diagnostic study, retrospective grading of endoscopic images using the 4-level Mayo subscore was performed by 2 independent reviewers with score discrepancies adjudicated by a third reviewer. Using 16 514 images from 3082 patients with UC who underwent colonoscopy at a single tertiary care referral center in the United States between January 1, 2007, and December 31, 2017, a 159-layer convolutional neural network (CNN) was constructed as a deep learning model to train and categorize images into 2 clinically relevant groups: remission (Mayo subscore 0 or 1) and moderate to severe disease (Mayo subscore, 2 or 3). Ninety percent of the cohort was used to build the model and 10% was used to test it; the process was repeated 10 times. A set of 30 full-motion colonoscopy videos, unseen by the model, was then used for external validation to mimic real-world application. Model performance was assessed using area under the receiver operating curve (AUROC), sensitivity and specificity, positive predictive value (PPV), and negative predictive value (NPV). Kappa statistics (κ) were used to measure agreement of the CNN relative to adjudicated human reference cores. The authors included 16 514 images from 3082 unique patients (median [IQR] age, 41.3 [26.1-61.8] years, 1678 [54.4%] female), with 3980 images (24.1%) classified as moderate-to-severe disease by the adjudicated reference score. The CNN was excellent for distinguishing endoscopic remission from moderate-to-severe disease with an AUROC of 0.966 (95% CI, 0.967-0.972); a PPV of 0.87 (95% CI, 0.85-0.88) with a sensitivity of 83.0% (95% CI, 80.8%-85.4%) and specificty of 96.0% (95% CI, 95.1%-97.1%); and NPV of 0.94 (95% CI, 0.93-0.95). Weighted κ agreement between the CNN and the adjudicated reference score was also good for identifying exact Mayo subscores (κ = 0.84; 95% CI, 0.83-0.86) and was similar to the agreement between experienced reviewers (κ = 0.86; 95% CI, 0.85-0.87). Applying the CNN to entire colonoscopy videos had similar accuracy for identifying moderate to severe disease (AUROC, 0.97; 95% CI, 0.963-0.969). This study found that deep learning model performance was similar to experienced human reviewers in grading endoscopic severity of UC. Given its scalability, this approach could improve the use of colonoscopy for UC in both research and routine practice.

336 – Using Deep Learning for Automated Grading of Endoscopic Disease Severity in Ulcerative Colitis

336 – Using Deep Learning for Automated Grading of Endoscopic Disease Severity in Ulcerative Colitis

P025 PERCEIVED DISEASE CONTROL AND TREATMENT SATISFACTION AMONG PATIENTS WITH ULCERATIVE COLITIS IN THE UNITED STATES

The goal of treatment in ulcerative colitis (UC) is to induce and maintain disease remission. Despite the available treatment options, ongoing challenges remain in managing patients with UC. The current study focused on the patient perspective by exploring how patients perceive their disease severity and treatment experiences and how these evaluations are related to their symptoms and patient-reported outcomes. Data were used from the 2016 UC Patient Study (Kantar Health, New York, NY), a cross-sectional, Internet survey of adult patients who report being diagnosed with UC and currently reside in the US. Measures include demographics, disease and treatment history, and patient-reported outcomes (e.g., Work Productivity and Activity Impairment [WPAI] questionnaire, Inflammatory Bowel Disease Questionnaire). Patients were identified from an Internet panel. The present study focused exclusively on patients who had a history of using an immunomodulator, a biologic, or a combination of 5-ASA and steroids. Statistical differences among groups were examined using chi-square (for symptoms) and one-way ANOVA tests (for WPAI variables). A total of 471 patients were included in this analysis (59.2% were female, mean age=50.6 years [SD=15.0], and 43.9% were currently using an immunomodulator or biologic for maintenance). Self-perceived severity was as follows: 49.0% considered themselves mild, 37.2% moderate, and 13.8% severe. Twenty-three of the 29 patient-reported symptoms varied significantly (p<.05) across levels of severity. Among patients who considered themselves mild, UC-related symptoms were common: diarrhea=44.2%, urgency=42.0%, tenesmus=22.1%, nocturnal bowel movements=20.8%, and rectal bleeding=20.3% (Table 1). Work and activity impairment also varied by level of severity (e.g., overall work impairment=21.8%, 56.7%, and 67.8% for mild, moderate, and severe disease, respectively; p<.05). Similar effects were observed as a function of treatment satisfaction (of which 390 patients had data). Specifically, 18.7% reported being either dissatisfied or neither satisfied nor dissatisfied, 22.1% reported being somewhat satisfied, and 59.2% reported being very/extremely satisfied with their current maintenance treatment. Twenty-three of the 29 patient-reported symptoms varied significantly (p<.05) across levels of satisfaction. Even among patients who were very/extremely satisfied with their treatment, UC-related symptoms were common: diarrhea=53.2%, urgency=48.1%, tenesmus=27.3%, nocturnal bowel movements=24.7%, and rectal bleeding=26.4%. Large proportions of patients perceive their UC disease severity to be mild and are very/extremely satisfied with their current treatment. Yet, even among these patients, many symptoms remain, and considerable impairment in work and daily activities are observed.

Fecal sST2 correlates with the disease severity of ulcerative colitis

Background/Aim. Ulcerative colitis (UC) is a chronic, relapsing inflammatory disease affecting the distal colon and rectum with complex pathogenesis and diagnosis, indicating the need for new diagnostic and prognostic markers. The aim of this study was to determine the fecal values of TNF- ?, IL-17, IL-10 and soluble protein ST2 (sST2) in the patients with UC and their relationship with clinicopathological aspects. Methods. The samples of stool of 80 patients with UC were analyzed. Concentrations of TNF-?, IL-17, IL-10 and sST2 were measured by ELISA. Results. Concentrations of TNF-?, IL-17 and sST2 were significantly increased in the feces of patients with the higher endoscopic, clinical and total Mayo score, as well as in the patients with an intense crypt destruction, erosion of the mucous membranes, architectural changes, neutrophil infiltration and eosinophil infiltration. The local value of anti-inflammatory cytokine IL-10 in liquid fraction of feces was increased in the patients with an advanced endoscopic stage of UC. The moderate positive correlation between the fecal sST2/IL-17 and the clinical and histological parameters of disease severity and also the strong correlation between sST2 and IL-17 was also observed in the feces of patients with UC. The analysis of receiver operating characteristic (ROC) curves showed that the optimal cut-off value for sST2 of 624.0 pg/g allows the discrimination of clinical stages of UC. Conclusion. The increased fecal value of sST2 in the UC patients with a higher endoscopic, clinical and histological stage of disease may be considered as a sign of the disease severity. The fecal values of sST2 can be used as a valuable marker for UC severity.

A [Glyco]biomarker that Predicts Failure to Standard Therapy in Ulcerative Colitis Patients.

There is a clinical need to identify biomarkers able to select patients who are most likely to develop aggressive/complicated disease, for early selection for appropriate therapy. Changes in the glycosylation profile of intestinal lymphocytic infiltrate were previously demonstrated to regulate T cell activity, being associated with disease severity in ulcerative colitis [UC] patients. We interrogated whether this heterogeneous expression of branched N-glycans in intestinal inflammatory infiltrate predicts therapy response early in disease course. The expression levels of the branched N-glycans in colonic biopsies collected around time of diagnosis from a well-characterised cohort of 131 UC patients were correlated with response to standard therapy. Receiver operating characteristic analysis and specificity/sensitivity were determined. Branched N-glycans levels around time of diagnosis predict non-response to conventional therapy with 75% specificity. Moreover, high levels of branched N-glycans predict 78% of UC patients who will display a favourable disease course [exclusively under 5-aminosalicylate therapy for more than 5 years of disease]. The best predictive performance was observed in severe UC patients with Mayo endoscopic subscore 3 and in those that were naïve to therapy. Multivariable analysis revealed that low levels of branched N-glycans and high levels of C-reactive protein [CRP] around time of diagnosis act as independent predictors of non-response to standard therapy. A powerful effect of the combined use of the branched N-glycans and CRP was observed. Our results reveal a potential [glyco]biomarker that predicts, early in the disease course, patients who will fail to respond to standard therapy, benefiting thereby from other therapeutic strategies such as biologics.

Platelet-to-lymphocyte Ratio and Neutrophil-to-lymphocyte Ratio Predict Mucosal Disease Severity in Ulcerative Colitis.

SummaryBackgroundWe investigated the sensitivity of neutrophil to lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as well as a combination of NLR and PLR to predict endoscopic disease severity based on mucosal assessment in ulcerative colitis (UC).MethodsThe study group consisted 104 patients with active UC, 104 patients in remission, and 105 healthy individuals. Disease activity was described with Rachmilewitz endoscopic activity index (EAI). Curve analysis was used to determine the optimal cutoff values of NLR and PLR for obtaining remission. The patients with both PLR and NLR values higher than the cutoff values were coded as »high risk,« those with one parameter higher were coded as »moderate risk«, those with both parameters lower than the cutoff values were coded as »low-risk« patients.ResultsThe mean NLR and PLR values in the endoscopically active disease group were higher than the others, with higher values in the endoscopic remission group compared with the control group (p<0.001). Rachmilewitz EAI in high-risk patients was significantly higher than that in others (p<0.001). In Cox regression analyses, moderate and high risk, high erythrocyte sedimentation rate and high EAI were found as independent predictors of endoscopic active disease.ConclusionsThis is the first study that investigated the use of NLR and PLR combination to assess endoscopic disease severity in UC. Either high NLR or PLR levels can predict active endoscopic disease. However, the use of these parameters in combination is more accurate in evaluating mucosal disease and inflammation in UC.

Altered expression of Tumor Necrosis Factor Alpha -Induced Protein 3 correlates with disease severity in Ulcerative Colitis

Ulcerative colitis (UC), an inflammatory disorder of the colon arises from dysregulated immune response towards gut microbes. Transcription factor NFκB is a major regulatory component influencing mucosal inflammation. We evaluated expression of Tumor Necrosis Factor Alpha Induced Protein3 (TNFAIP3), the inhibitor of NFκB activation and its associated partners ITCH, RNF11 and Tax1BP1 in inflamed mucosa of UC patients. We found highly significant up-regulated mRNA expression of TNFAIP3 that negatively correlated with disease activity in UC. mRNA levels of ITCH, RNF11 and Tax1BP1 were significantly down-regulated. Significant positive correlation with disease activity was noted for Tax1BP1. All four genes showed significant down-regulation at protein level. mRNA levels of inducers of TNFAIP3 expression, NFκB p65 subunit and MAST3 was determined. There was significant increase in p65 mRNA expression and down-regulated MAST3 expression. This suggested that increase in NFκB expression regulates TNFAIP3 levels. Deficiency of TNFAIP3 expression resulted in significant up-regulation of NFκB p65 sub-unit as well as its downstream genes such as iNOS, an inflammatory marker, inhibitors of apoptosis like cIAP2 and XIAP and mediators of anti-apoptotic signals TRAF1 and TRAF2. Taken together, decreased expression of TNFAIP3 and its partners contribute to inflammation and up-regulation of apoptosis inhibitors that may create microenvironment for colorectal cancer.