Disease Activity In Ulcerative Colitis Research Articles

Ultra-Processed Food, Disease Activity, and Inflammation in Ulcerative Colitis: The Manitoba Living With IBD Study.

The purpose of this study was to investigate the relationship between ultra-processed food (UPF) consumption and (i) symptomatic disease and (ii) intestinal inflammation among adults with inflammatory bowel disease (IBD). We identified participants (Crohn's disease [CD] and ulcerative colitis [UC]) from the Manitoba Living with IBD study. Active disease was defined using the IBD Symptom Inventory (score >14 for CD; >13 for UC); fecal calprotectin was measured for intestinal inflammation (>250 μg/g). Diet data were collected using the Harvard Food Frequency Questionnaire. UPF consumption was determined by the NOVA classification system. Percentage of energy consumption from UPFs was calculated and divided into 3 tertiles (T1 = low; T3 = high). Multiple linear regression analysis was used for active disease and inflammation predicted by UPF consumption. Among 135 participants (65% with CD), mean number of episodes of active disease (14.2 vs 6.21) and active inflammation (1.6 vs 0.6) was significantly higher among participants with UC in T3 compared with T1 of UPF consumption ( P < 0.05). When adjusting for age, sex, disease type, and duration, number of episodes of active disease was lower in T1 compared with T3 (β = -7.11, P = 0.02); similarly, number of episodes of intestinal inflammation was lower in T1 (β = -0.95, P = 0.03). No significant differences were observed among participants with CD. UPF consumption may be a predictor of active symptomatic disease and inflammation among participants with UC. Reducing UPF consumption is a dietary strategy that can be suggested for minimizing symptoms and inflammation among people living with IBD.

Assessing the correlation between fecal calprotectin, blood markers and disease activity in pediatric inflammatory bowel disease.

Crohn's disease (CD) and ulcerative colitis (UC) are the 2 main types of inflammatory bowel disease (IBD), a chronic inflammatory condition of the gastrointestinal tract. Management of IBD necessitates frequent clinical monitoring, including blood tests and occasionally endoscopy. Fecal calprotectin (FC) is a non-invasive measurement of luminal inflammatory activity, and can therefore be used as a useful monitoring tool. This study aimed to assess the relationship between FC, IBD activity indices and the commonly used blood markers in pediatric IBD. Electronic patient records were accessed to retrospectively collect patient data from a tertiary pediatric hospital from 2015-2021. CD and UC disease activity was quantified using the Pediatric CD Activity Index (PCDAI) and Pediatric UC Activity Index (PUCAI), respectively. The Paris classification was used for phenotype identification. A total of 208 patients were included in the study, 115 with CD (18% <10 years and 82% 10-17 years) and 93 with UC (32% <10 years and 68% 10-17 years). There was a positive correlation between FC and PCDAI (rs=0.546, P<0.001) and between FC and PUCAI (rs=0.485, P<0.001). FC and activity indices were correlated positively with inflammatory markers/platelets and negatively with albumin and hemoglobin. FC correlated positively with PCDAI in all CD phenotypes, including isolated ileal disease. In pediatric IBD, FC shows a positive correlation with the clinical picture and blood markers in all disease phenotypes, and can provide an accurate non-invasive measure of disease activity.

USEFULLNESS OF SERUM LEUCINE-RICH ALPHA2-GLYCOPROTEIN AND FECAL CALPROTECTIN ASSURROGATE MARKERS IN ULCERATIVE COLITIS

Abstract BACKGROUND AND AIM Serum Leucine-rich alpha-2 glycoprotein (LRG) was identified as a novel biomarker for rheumatoid arthritis and IBD by using a proteomics approach. Several studies have suggested that serum LRG levels and fecal calprotectin (fCal) were correlated with clinical activities in patients with ulcerative colitis (UC). We compared utility of these biomarkers for monitoring disease activity in UC. METHODS A single-center observational study was conducted at Kyushu University Hospital. A total of 101 patients who underwent colonoscopy during the period from February to December 2021 were enrolled. The associations between endoscopic and histological activity and biomarkers were investigated. Endoscopic activity was defined as Mayo endoscopic score (MES) of 1 or less for mucosal healing and 0 for complete mucosal healing. For histological activity (n=90), Geboes score of 2 or less was defined as histological remission. RESULTS Subjects ranged in age from 16 to 80 years (35 males and 66 females). There were 63 cases of total colitistype, 32 cases of left-sided colitis type, and 6 cases of proctitis type. The MES at enrollment were as follows: MES 0 in 41 cases, MES 1 in 33 cases, MES 2 in 19 cases, and MES 3 in 8 cases. In comparison between the mucosal healing and non-mucosal healing groups, LRG was significantly lower in the mucosal healing group (p&amp;lt;0.0001). The correlation coefficient of LRG with MES was r=0.614 (p&amp;lt;0.0001), which was higher than that of fCal, r=0.414 (p&amp;lt;0.0001). In ROC analysis with mucosal healing as the outcome, the AUC and cut-off value of LRG were 0.781 and 17.9 μg/ml, respectively, and for fCal were 0.850 and 396 μg/g, respectively. In the ROC analysis with complete mucosal healing as the outcome, the AUC for LRG was 0.690, which was lower than the AUC of 0.846 for fCal . When compared by histological remission, LRG was lower in the histological remission group (p&amp;lt;0.001). In the ROC analysis with histological remission as the outcome, the AUC for LRG was 0.722 (cutoff value 14.2 μg/ml) and for fCal was 0.837 (cutoff value 119 μg/g). CONCLUSION Both LRG and fCal are valuable biomarkers reflecting disease activity in UC.

P336 Exploring Extracellular Matrix Markers in Ulcerative Colitis: Degradation and Formation Insights

Abstract Background The gold standard for assessing disease activity in ulcerative colitis (UC) is endoscopy, which is uncomfortable for the patient, and only evaluates the superficial layers of the colon. Intestinal extracellular matrix (ECM) remodeling is highly dynamic during disease activity and blood spillover of ECM components might reflect transmural disease burden. The aim of this study was to evaluate baseline serum markers of ECM formation (PRO-C11, PRO-C22, and PRO-C7) and degradation (C7M) to assess disease activity and treatment response in UC. Methods Forty-nine UC patients with active disease and 50 healthy controls (HC) were included. All underwent endoscopy and blood sampling at inclusion. UC patients additionally had fecal calprotectin (FCP) measured at baseline and had treatment adjusted at the discretion of the attending physician. Subsequent follow up of UC patients included clinical activity score, FCP, and blood samples at 3 and 6 months as well as an endoscopy at 6 months. Ulcerative Colitis Endoscopic Index of Severity (UCEIS), total Mayo score (TMS), and disease extent (E1-E3) was registered. Response was defined as a reduction from severe to moderate or mild disease based on TMS. If no follow-up endoscopy was performed (n=9), partial Mayo was used. Spearman’s correlation and one-way-ANOVA with Turkey correlation and correction for multiple testing were applied for statistical analysis. Results All markers of ECM degradation and formation were elevated in patients with severely active UC measured by both UCEIS and TMS compared to HC (adjusted p&amp;lt;0.0001 for each marker). CM7 and PRO-C22 differentiated moderate from severe UC by TMS (p&amp;lt;0.0001) and UCEIS (p&amp;lt;0.05) (Figure 1A-B). Baseline C7M, PRO-C7, and PRO-C11 correlated with CRP (Spearman’s: r=0.82, p&amp;lt;0.0001; r=-0.45, p=0.0012; and r=-0.33, p=0.032, respectively). None of the markers correlated with FCP. Elevated C7M, PRO-C7, and PRO-C11 levels for E3 could differentiate E3 from E1 (Difference ng/ml: 3.89 (SE of diff: 1.47), 13.15 (4.55), 10.08 (4.09), respectively, all p&amp;lt;0.05) (Figure 1C-E). Remission was achieved in 18/49 patients at 6 months. Both C7M and PRO-22 exhibited acceptable discriminative capabilities at baseline for 6-month TMS between remission and non-remission (AUC 0.72 (95% CI 0.58-0.87) p=0.01 and AUC 0.68 (95% CI 0.53-0.83) p=0.04, respectively) (Figure 1F-G). Conclusion This study demonstrates that ECM markers correlate with disease activity, disease extent, and predict future disease outcome in UC. ECM markers hold great promise as they provide a 'window' into transmural tissue remodeling and inflammatory and fibrotic burden, warranting further investigation.

P436 The AI based Red Density score is correlated with the established and new histological indices for Ulcerative Colitis in an independent cohort

Abstract Background Red Density (RD) is an automated endoscopic tool that is developed for the objective evaluation of disease activity in ulcerative colitis (UC). The initial development integrated histological disease activity based on Robarts histological index (RHI) in the machine learning algorithm. New histological scores for UC have been developed since. The aim of this study was to establish the correlation between RD and the Nancy histological index (NHI) and PICaSSO Histologic Remission Index (PHRI). Methods Patients included in 4 centers in the ongoing PROCEED-UC study (NCT04408703) had assessment with RD in the rectum and sigmoid at baseline, w52 or early termination visit. Biopsies were taken according to protocol. Biopsies were scored for the Geboes score (GBS), RHI, NHI, PHRI in a blinded way after initial scoring convention training. Correlation was tested on patient level between mean RD per segment and the different histological indices based on Spearman correlation. Results In total 96 patients from 4 centers were included representing 2634 RD images from 400 colonic segments with biopsies and corresponding RD score. Mean (± SEM) rectal RD score was 32.7 (± 4.54), 33.69 (± 5.25) and 64.86 (± 31.71) at baseline, w52 and ET respectively. Mean sigmoidal RD score was 38.13 (± 3.68), 42.82 (± 11.80) and 77.33 (± 24.65) at baseline, w52 and ET respectively. Analysis based on the segment with the highest mean RD score per patient showed significant correlation with NHI (r=0.60, p&amp;lt;0.0001), PHRI (r=0.62, p&amp;lt;0.0001). In the rectum the RD score at all time points correlated significant with NHI (r =0,53, p&amp;lt;0.0001) and PHRI (r=0.63, p&amp;lt;0.0001). Similar correlation was seen in the sigmoid for NHI (r=0.51, p&amp;lt;0.0001) and PHRI (r=0.22, p0.0108). A RD score of &amp;lt;57.5 (Likelihood Ratio (LR) 4.176; AUC 0.7820 (95CI 0.7047 - 0.8593), p&amp;lt;0.0001) was associated with histological remission based on NHI (&amp;lt;2) and a RD score of &amp;lt; 64.5 (LR 9.821; AUC 0.8133 (95%CI 0.7053 - 0.9212), p&amp;lt;0.0001) with histological remission based on PHRI (=0). The current dataset demonstrated to be stable in line with the previously established RD cut-off with GBS and RHI. 1 Conclusion In an independent cohort of patients with UC the correlation with the established and new histological indices for UC is confirmed. This underlines the value of RD as an objective endoscopic tool for the assessment of histological and endoscopic disease activity in UC. Ref 1: Bossuyt P, Nakase H, Vermeire S, De G, Eelbode T, Ferrante M, et al. Automatic, computer-aided determination of endoscopic and histological inflammation in patients with mild to moderate ulcerative colitis based on red density. Gut. 2020;69:1778–86.

P472 A Real World Practice of Intestinal Ultrasound in the Monitoring of Disease Activity in Ulcerative Colitis

Abstract Background Intestinal ultrasound (IUS) has emerged as an important monitoring tool in the clinical course of ulcerative colitis (UC). Previously known factors about UC have been considered in terms of the associations with IUS. However, a few studies reported about the associations between the findings of IUS and clinical factors. Methods We performed a multi-center, cross-sectional study of patients with UC who received IUS and clinical exams including endoscopy simultaneously. The primary endpoint was the association between endoscopic disease activity as Mayo endoscopic score (MES) and IUS finding as Milan ultrasound criteria (MUC). The secondary endpoint comprised the various clinical factors associated with MUC. Patients with MUC&amp;lt;6.2 were defined as low MUC group and others as high MUC group. Results A total of 35 patients were enrolled in this study. The numbers of Low- and high-MUC groups were 23 and 12, respectively. The median age in each group was 41 and 53 years old. The portion of male sex in each group was 57% and 75%. There were no significant differences in terms of body mass index, onset age, disease duration, current medication such as 5-aminosalicylic acid, steroid, immunomodulator, and biologics and small molecules between both groups. Compared with low and high MUC groups, endoscopic remission was more significantly associated with the low MUC group than the high MUC group (35% vs. 0, p = 0.032). In addition, the rate of disease activity ranged from remission to mild, as tolerable clinical activity, was also significantly higher in the low MUC group than the high MUC group (91% vs. 58%, p = 0.033). Other outcomes such as symptomatic remission, histologic remission, and biochemical response revealed similar rates between the two groups. Conclusion Low MUC of IUS in the patients with UC showed significant clinical association such as endoscopic remission and tolerable clinical activity. This study is now ongoing prospective research and further investigation into the relationship between IUS and clinical outcomes of UC will elicit robust results.

P131 Therapeutic effects of KPG-818 in a trinitrobenzene sulfonic acid - induced mouse Crohn's/Ulcerative Colitis model

Abstract Background Immunomodulatory drugs have the potential therapeutic benefit not only in malignancy but also in diseases characterized by an inflammatory phenotype. In inflammatory bowel diseases (IBD), colonic inflammation results from dysregulation of the mucosal immune responses to intestinal flora together with genetic and environmental factors. Inflammatory cytokines are implicated in pathogenesis of IBD. Treatments for IBD that improve clinical outcomes and limit adverse effects are needed. KPG-818 is a novel generation of lenalidomide derivative and small molecule immunomodulatory drug. KPG-818 is currently under clinical development for therapy of multiple myeloma, lymphoma (phase 1), and systemic lupus erythematosus (SLE) (phase 2a). Remarkable immunomodulatory effects of KPG-818 are observed in SLE patients. In preclinical studies, KPG-818 significantly inhibits inflammatory cytokines interleukin-6 and TNF-α in human peripheral blood mononuclear cells, inhibits tumor growth in multiple myeloma and lymphoma xenograft tumor models. Here we report the significant therapeutic effects of KPG-818 in a chronic Crohn’s/ulcerative colitis mouse model. Methods Trinitrobenzene Sulfonic Acid (TNBS) was intra-colonially administered to induce Balb/c mouse Crohn’s/ulcerative colitis model at 50 mg/kg, once a week for 4 weeks. KPG-818 was orally administered at doses of 0.03, 0.12, 0.4, and 1.0 mg/kg, once a day for 6 consecutive weeks. Upadacitinib served as a positive control drug. Vehicle solution served as a negative control. To evaluate the therapeutic effects of the KPG-818, disease activity index (DAI) of ulcerative colitis, the degree of weight loss, fecal morphology, and rectal bleeding were scored once every other day for six consecutive weeks. At the end of the study, colonic samples were collected for gross observation and scoring of macroscopic damage, measurement of length and weight, and histopathological diagnosis and scoring. At the end of study, peripheral blood samples were also collected for analyses of immune cells and cytokines. Results Compared to the vehicle control, KPG-818 significantly improved the body weight loss, disease activity of ulcerative colitis, gross degree of colorectal injury, pathological lesions of colorectal tissue, inhibited the inflammatory cytokines in a dose-response manner. The effective dose was as low as 0.03 mg/kg. KPG-818 showed similar therapeutic effects to Upadacitinib. Conclusion In this mouse model of chronic Crohn’s/ulcerative colitis, KPG-818 showed remarkable therapeutic effects in a dose-dependent manner. These data encourage the clinical evaluation of KPG-818 in inflammatory bowel diseases.

P280 Comparative responsiveness of disease activity indices in moderately-to-severely active Ulcerative Colitis: a post-hoc analysis of the UNIFI trial

Abstract Background Clinical, endoscopic, histological, and composite instruments are used to measure disease activity in ulcerative colitis (UC). We compared responsiveness of the Mayo Clinic Score (MCS), modified Mayo Clinic Score (mMS), partial Mayo Clinic Score (pMS), Robarts Histopathology Index (RHI), and UC-100 score after treatment with ustekinumab in patients with moderately-to-severely active UC. Methods Publicly available data from the phase 3 UNIFI induction trial (NCT02407236) comparing the efficacy and safety of ustekinumab versus placebo in patients with moderate-to-severe UC were obtained from Vivli (Vivli ID #7549) and Yale University Open Data Access Project (#2021-4848). Post-hoc analyses were performed on patient level data to ascertain outcomes of interest. Treatment assignment was the criterion for change in evaluation of responsiveness, which was quantified using the probability of a treated patient having a larger change than a placebo patient (win probability [WinP]) and estimated using nonparametric methods. Extent of responsiveness was interpreted according to Cohen’s benchmarks as very small (WinP&amp;lt;0.56); small (0.56≤ WinP&amp;lt;0.64); medium (0.64≤ WinP&amp;lt;0.71); and large (WinP≥0.71). Results Data from 961 patients with moderately-to-severely active UC randomised in UNIFI were included. At baseline, 319 patients received placebo and 624 patients received ustekinumab. A total of 912 (94.9%) patients completed the induction trial. Overall mean baseline index scores were: MCS 8.9 (±1.6), mMS 6.6 (±1.3), pMS 6.2 (±1.4), RHI 16.6 (±8.1), and UC-100 score 71.4 (±16.5) (Table). The UC-100 demonstrated a large degree of responsiveness (WinP 0.72 [95% CI: 0.66, 0.78]). The MCS (0.68 [0.62, 0.73]), mMS (0.69 [0.63, 0.75]), and pMS (0.65 [0.59, 0.71]) demonstrated similar, medium effect sizes (all comparisons p&amp;gt;0.05) (Figure). The RHI alone had a relatively small effect size (WinP 0.63 [0.56-0.70]). Among individual UC-100 components (Mayo Clinic stool frequency subscore, Mayo Clinic endoscopic subscore, and RHI), the endoscopic score was most responsive (WinP 0.59 [0.36-0.82]). The combination of endoscopy and RHI was associated with a medium degree of responsiveness (WinP 0.69 ([0.34, 1.00]). Conclusion UC disease activity indices are similarly responsive to change. Depending on trial design and measurement feasibility, different instruments can be considered optimal for evaluation of efficacy. The mMS is similarly responsive to the MCS without including the physician global assessment and may be more appropriate for determining trial eligibility and defining primary endpoint, whereas the UC-100 may be more appropriate for measuring treatment effect when an objective continuous measure is needed.

P1041 Coconut water modulates dietary potassium and gut microbiome to induce remission in ulcerative colitis: randomized controlled trial

Abstract Background High potassium intake is associated with decreased risk of inflammatory bowel disease(IBD), urinary potassium has been correlated with disease activity in ulcerative colitis(UC), and gut microbiome modulation improves outcomes in UC. We evaluated coconut water as potassium rich diet and gut microbiome modulator in patients with mild-moderate UC. Methods This single-center double-blind placebo-controlled trial randomized patients with mild-moderate (simple clinical colitis activity index-SCCAI:3–9) endoscopically active UC (ulcerative colitis endoscopic index of severity-UCEIS&amp;gt;1) in 1:1 ratio to coconut water + standard medical therapy-SMT(CW) vs placebo + SMT. 400ml of coconut water (200-250mg potassium/100ml) was administered for 8 weeks. Primary outcome measure was clinical remission (SCCAI ≤ 2) and secondary outcome measures were clinical response (SCCAI decline ≥ 3) and adverse events at 8 weeks. Microbiome was analyzed at baseline and 8 weeks. Results Of 121 patients screened, 95 were included for modified intention to treat analysis(49-CW, 46-placebo)[mean age-37.2 ± 11.2years; males-54.1%; disease duration-48 (IQR:24–90) months; pancolitis - 26.1%; SCCAI-5 (IQR:4 – 6); UCEIS-4 (IQR:3 – 5)]. There was significant increase in dietary potassium and decline in sodium/potassium ratio at 8 weeks in CW. Clinical response [57.1% vs 28.3%, p=0.01, OR-3.4 (95%CI:1.4 – 7.9)], remission [53.1% vs 28.3%, p=0.02, OR-2.9(95%CI:1.2 – 6.7)] and proportion of patients with fecal calprotectin (FCP)&amp;lt;150μg/g [53.6% vs 14.3%, p=0.01, OR-6.9(95%CI:1.6 – 28.9)] were significantly higher in CW. The relative abundance of bacterial taxa which had a significant or trend towards negative correlation with SCCAI, UCEIS, or FCP, increased at 8 weeks in CW. Adverse events were comparable and no patient developed hyperkalemia. Conclusion Coconut water increased dietary potassium, modulated the gut microbiome and was more effective than placebo for induction of remission in mild-moderate UC.

P412 Faecal Calprotectin as a predictor of endoscopic and histologic remission in patients with Ulcerative Colitis

Abstract Background Faecal calprotectin (FCP) is a reliable surrogate marker for disease activity in ulcerative colitis (UC). However, there are no consensus cut-off values for histoendoscopic remission. The aim of the study is to correlate FCP with Mayo Endoscopic Score (MES) and histological disease activity (Geboes score) of UC patients in clinical remission. Methods We performed a prospective study including adult UC patients at the McGill IBD Center between 2013 and 2017. Patients in clinical remission (partial Mayo score ≤2) or disease relapse, undergoing endoscopy for disease activity or dysplasia surveillance, were enrolled. Before bowel preparation, FCP was collected. MES was documented during colonoscopy. Biopsies were taken throughout the colon and histological activity was assessed using Geboes score (GS) by a blinded expert gastrointestinal pathologist. Results The study included 253 patients, of which 117 (46%) were male with a mean age of 38.2 years (standard deviation [SD] ± 24.8). 46% of the patients had pancolitis at the time of colonoscopy. 5-aminosalicylate were used by 68.4% of patients while 20.9% were on immunomodulators, 19% on biologics and 0.4% on small molecules as treatment. Regarding endoscopic correlation, it showed that an FCP ≥ 200 μg/g predicts MES &amp;gt; 1 despite clinical remission, yielding sensitivity of 59% and specificity of 74%. A FCP ≥ 123 predicts MES &amp;gt; 0 despite clinical remission (58% sensitivity and 70% specificity), also aiding to differentiate MES 0 from MES 1 (61% sensitivity and 70% specificity). As to histologic correlation, a FCP ≥ 80 μg/g identified histological disease activity using Geboes criteria (GS score &amp;gt; 3.1) in patients with clinical remission, yielding 64.7% sensitivity, 58.7% specificity and 77% positive predictive value (Figure 1). When using a GS score threshold of &amp;gt; 2, a cut-off value of FCP ≥ 50 μg/g, appears to be the most clinically relevant to identify patients in clinical remission who continue to have active histologic inflammation, with an 49.6% sensitivity, 41.6% specificity and 40% positive predict value. Results are summarized in Table 1. Conclusion FCP correlates very well with endoscopic and histologic disease activity and can be used as a surrogate marker for disease activity. Our study prospectively demonstrated the optimal cut-off values helping to discriminate endoscopic healing and histologic remission.

P357 Automated assessment of histological disease activity in Ulcerative Colitis using a deep learning algorithm

Abstract Background Assessment of histological disease activity in patients with ulcerative colitis (UC) is becoming more important. Therefore, the DCA score was developed for use in clinical practice. Distribution (D), chronicity (C) and activity (A) are each scored on a three-point scale with distribution being dependent on the percentage of biopsy area affected by inflammatory changes. A major problem for implementation of any score is interobserver heterogeneity. To overcome this hurdle, we developed a deep learning algorithm to automatically compute the DCA score. Methods A retrospective cohort was created consisting of 117 adult patients with ulcerative colitis from which biopsies were taken during a colonoscopy performed in the setting of routine clinical evaluation (training set of 537 slides). From 75 cohort patients, an additional set of biopsies was available (test set of 299 slides). An expert gastrointestinal pathologist performed the DCA score. The model was trained on H&amp;E-stained whole slide images scanned at 40x (0.243-μm pixel) resolution. Training was performed in a weakly supervised multiple-instance learning setup, using slide-level labels without region of interest annotations. The features from the convolutional neural network-based model trained at 2.5x, 5x, and 10x magnification were incorporated using a random forest classifier for final prediction. Model accuracy was evaluated using the test set. Results The algorithm differentiates between normal and inflamed with an accuracy of 90.9% (Table 1). Model performance from features aggregated across all magnification levels (i.e., 2.5x, 5x, and 10x) was superior to features from individual levels. This can be explained with the help of GradCam heatmaps (Figure 1), where we show that features learned at different magnification levels correspond to different aspects of histological changes in UC. The multiple instance approach did not appear to detect crypt abscesses, which may have resulted in a relatively poor performance in differentiating A1 from A2. The model accuracy for the 9-class DCA was 64.8%. Conclusion The algorithm first appears to assess architectural distortions at lower magnification and then the presence of cellular elements like neutrophils at higher magnification. This closely mirrors the approach of pathologists. The present model automates the scoring process and by supporting the daily diagnostic practice highlights the potential of deep learning technologies in assessment of histological disease activity in UC.

P138 Novel serum markers for predicting disease activity in ulcerative colitis: results from a retrospective case-control study

Abstract Background Commonly used serum or faecal markers, such as C-reactive protein (CRP) and feacal calprotectin have several limitations and do not always correlate well with the degree of mucosal inflammation in the intestine as established by endoscopy. The aim of the current study was to evaluate the utility of a panel of serum markers (Visfatin, serum amyloid, LRG1, MMP-1, MMP-2, TFF3, Lipocalin-2 (NGAL), IL-6, IL-4, IL-7, IL-17) in predicting mucosal inflammation in ulcerative colitis(UC) patients. Methods We conducted an unmatched case-control retrospective study. Patients were selected consecutively, based on their enrollement date, from a prospective IBD cohort. We selected two groups of UC patients, each of them with active disease at baseline and different outcomes during follow-up: mucosal healing and persistant disease activity, as resulted from clinical and endoscopic evaluation. Inflammatory burden was investigated using the C-reactive protein and endoscopic activity was reported using the Mayo endoscopic score. Quality of life was also evaluated at each visit using The Short Inflammatory Bowel Disease Questionnaire (SIBDQ). Clinical disease activity was quantified using the partial Mayo score. Clinical remission was defined as a partial Mayo score &amp;lt; 2. Endoscopic activity was assessed using the Mayo endoscopic score[i] . Mucosal healing was defined as Mayo endoscopic score of 0. The selection of investigated biomarkers was based on the results of a systematic review previously published by the research team [i] State M, Negreanu L, Voiosu T, Voiosu A, Balanescu P, Mateescu RB. Surrogate markers of mucosal healing in inflammatory bowel disease: A systematic review. World J Gastroenterol. 2021 Apr 28;27(16):1828-1840. doi: 10.3748/wjg.v27.i16.1828. Results 84 serum samples from 42 patients were retrospectively analyzed (21 patients with mucosal healing and 21 patients with persistant activity during follow-up). Lipocalin proved to be a reliable marker for the noninvasive assessment of endoscopic activity, with 90% sensitivity and 95% specificity at a cut-off level of 0,421μg/ml (AUROC 0,677). The combination of lipocalin, age, gender and BMI (Figure 1) is a good predictor of persistant activity during follow-up (AUROC 0.87, 95% CI, 0.762-0.979). Conclusion Our findings provide support for the use of lipocalin as a surrogate marker for mucosal inflammation. The combination of lipocalin, age, gender and BMI might be useful for guiding treatment and monitoring decisions.

P355 Correlation of Intestinal Ultrasound with histological activity in patients with Ulcerative Colitis

Abstract Background Histological remission in ulcerative colitis (UC) is considered a therapeutic target predictive of favorable clinical outcomes. Intestinal ultrasound (IUS) represents an imaging tool that is well correlated with endoscopy and can accurately define disease activity in UC. There is a major gap in the international literature examining the potential link between activity indices on IUS and histological findings in UC1. We aimed to evaluate the correlation of the Milan Ultrasound Criteria (MUC) with Nancy Histological index (NIH) in patients with UC. Methods We performed a cross-sectional study that included consecutive patients with established diagnosis of UC. All patients underwent colonoscopy with biopsy samples, as well as IUS within 3 days of one another. Endoscopic activity was defined as an endoscopic mayo score (EMS) &amp;gt; 0, while histological activity was defined as NHI &amp;gt; 12. Active disease on IUS was calculated on the most affected bowel segment by MUC [MUC = 1.4 × Bowel wall thickness (BWT) in mm) + 2 × Bowel Wall Flow (BWF); BWF = 1 if present, or BWF = 0 if absent] 3. Activity on IUS was defined as a MUC score &amp;gt; 6.2. For maximum accuracy, the most affected bowel segments on endoscopy and IUS were matched. On the day of endoscopy, partial mayo score (PMS) was calculated (PMS &amp;gt;1 corresponded to clinical activity), and C-reactive protein (CRP) was recorded. Results A total of 45 patients were included (table 1). We observed a strong correlation between MUC and endoscopic activity [ρ: 0.802 (p&amp;lt; 0.001)], as well as between MUC, PMS and CRP [ρ: 0.743 (p&amp;lt; 0.001) and ρ: 0.798 (p&amp;lt; 0.001)] respectively. We revealed a strong correlation between MUC and NHI [ρ: 0.811 (p&amp;lt; 0.001)]. A MUC &amp;gt; 6.2 possessed 74.3% sensitivity, 90% specificity, 96.3% PPV and 50%, NPV (p&amp;lt;0.001) in predicting histological activity (Nancy&amp;gt;1). At the optimal cut-off value of 5.67, MUC displayed a sensitivity of 97.1% and a specificity of 90% [(AUC: 0.973, 95% CI: 0.918-1.000, (p&amp;lt;0.0001) – fig 1] in predicting histological activity (NHI&amp;gt;1), in patients with UC. Conclusion Intestinal ultrasound represents a promising non-invasive tool that can accurately define histological activity in patients with UC. Further studies are needed to confirm the aforementioned results.

P229 Comparison of Different Histological Scoring Systems for Ulcerative Colitis [Nancy Histological Index, Robarts Histopathology Index and IBD-DCA (Inflammatory Bowel Disease-Distribution, Chronicity, Activity Score)] Among Specialists in GI Pathology and General Pathologists Pre- &amp; Post Workshop

Abstract Background Histopathology is an emerging treatment target and an important parameter in predicting clinical outcomes of patients with ulcerative colitis (UC). Histological scoring indices Nancy Histological Index (NHI) and Robarts Histopathology Index (RHI) have been developed and validated for UC. We aim to compare the inter-observer reliability of NHI, RHI and the recently described Inflammatory Bowel Disease-Distribution, Chronicity, Activity (IBD-DCA) Score among gastrointestinal (GI) pathologists versus general pathologists pre- and post-workshop to determine the scoring system with the best reproducibility. Methods Digital whole slide images of 20 H&amp;E-stained biopsies of ulcerative colitis (UC) cases are scored independently by 6 GI pathologists and 44 general pathologists that attended the Singhealth GI Pathology Course 2023 using NHI, RHI and IBD-DCA on the digital Pathpresenter platform. The 44 course participants performed the scoring before the course and again after attending a 3-hour IBD workshop on the assessment of histological remission using these 3 scoring systems. Data tabulation using “Free Online Surveys” platform is collated and intraclass correlation coefficient (ICC) of each component of the scoring indices is calculated. The ICC values of &amp;lt;0.5, 0.5–0.75, 0.75–0.9, and &amp;gt;0.9, indicate ‘poor’, ‘moderate’, ‘good’, and ‘excellent’ agreement, respectively. Results There is good inter-observer reliability for IBD-DCA ‘Activity’ component (ICC 0.85) and NHI (ICC 0.83) among GI pathologists while lBD-DCA ‘Distribution’ component (ICC 0.395) has the poorest agreement. Poor to moderate inter-observer reliability for all 3 scoring systems (ICC 0.4 – 0.6) is seen among the 44 participants pre-workshop with an observed post-workshop improvement, achieving best agreement for the NHI, ‘lamina propria neutrophils’ component of RHI and IBD-DCA ‘activity’ component (ICC 0.7). Conclusion GI pathologists are generally consistent in assessing disease activity in UC with good inter-observer reliability for NHI (a scoring system with an emphasis on activity grade) and only the ‘activity’ component of the IBD-DCA. Our study confirms NHI as a reliable scoring system for UC with the best reproducibility and favour its application to assess histological response in routine clinical practice to help gastroenterologists better manage patients with UC. We have also demonstrated that improvement in NHI scoring reproducibility can be achieved after training workshop for pathologists less familiar with the application of IBD histological scoring.

P235 Correlation of mental and psychological status to disease activity in patients with Inflammatory Bowel Disease using The Symptom Checklist -90- Revised Questionnaire (SCL90R)

Abstract Background Inflammatory Bowel Disease can affect mental health. There is no evidence that stress is a direct cause of the disease. Most Inflammatory Bowel Disease patients describe an emotional impact, mainly feelings of depression and anxiety. Many questionnaires used to assess anxiety in those patients including Symptom Checklist -90-Revised Questionnaire. This research aimed to investigate Correlation of mental and psychological status to disease activity in patients with Inflammatory Bowel Disease using Symptom Checklist -90-Revised Questionnaire. Methods The study included one hundred patients (50 Crohn's Disease patients – 50 Ulcerative Colitis patients). Detailed history taking, systemic physical examination, laboratory investigations, Colonoscopy, Symptom Checklist -90-Revised Questionnaire. A self-report psychometric instrument (questionnaire) for every patient. Results The mean age of Crohn’s Disease patients was 24,2 years +/- SD 3,6 years. In Ulcerative Colitis patients the mean age was 28,5 years +/- SD 7,3 years. No age or gender relation could be detected with Symptom Checklist -90-Revised Questionnaire score in both groups, The study showed a direct correlation of Crohn's Disease Activity Index (CDAI) and endoscopic activity (Simple Endoscopic Score) (SES) to Symptom Checklist -90-Revised Questionnaire. There was direct correlation of Ulcerative Colitis disease activity (Simple Clinical Colitis Activity Index) (SCCAI) and Endoscopic activity (Ulcerative Colitis Endoscopic Index of Severity) (UCEIS) to Symptom Checklist -90-Revised Questionnaire. Conclusion There is a direct correlation of disease activity and Endoscopic activity in Ulcerative Colitis and Crohn's Diseases to Symptom Checklist -90-Revised Questionnaire.

P428 Nutritional, Muscular status and micronutrient deficiencies in patients with Inflammatory Bowel Disease

Abstract Background Malnutrition and micronutrient deficiencies are common in inflammatory bowel disease (IBD). Nutrient deficiencies increase the morbidity and complications of IBD. The aim of this study was to evaluate the nutritional and muscular status and identify micronutrient deficiencies of patients with IBD receiving treatment. Methods A total of 105 patients with IBD were enrolled prospectively in the department of gastroenterology and pediatrics from June 2019 to October 2021. To obtain objective data, iron, ferritin, phosphate, folate, Mg, 25-OH vitamin D, vitamin B12, and Zinc were measured in the patient's serum. In addition, body composition analysis was performed using bioelectrical impedance analysis to gain information regarding muscular status. Results There were 51 patients with ulcerative colitis (UC), 54 with Crohn's disease (CD), and the gender ratio (M:F) was 54:51. The average age was 37±18 years, which was significantly lower in patients with CD than UC (28.6±15.9 vs. 45.3±16.3, p&amp;lt;0.001). The mean body mass index (BMI) was 22.0 ± 3.7 kg/m2, lower in patients with CD than UC (21.2 ± 3.8 kg/m2, vs. 22.0 ± 3.3 kg/m2, p=0.030). The disease activity of the patients was 64.8% in remission, with 17.1% mild, 15.2% moderate, and 2.9% severe. In the UC and CD patient groups, skeletal muscle index(SMI) and adjusted skeletal muscle mass were lower in patients with CD compared to UC.(SMI : 35.8±5.5 vs. 32.8±4.7 %, p&amp;lt;0.004, adjusted skeletal muscle : 8.2±1.9 vs. 7.0±1.5 kg/m2, p&amp;lt;0.001) However, there was no difference of SMI and adjusted skeletal muscle according to disease activity in both UC and CD patients (Table 1). Iron was lower in patients with CD compared to UC (63.3 ± 42.5 vs. 82.8 ± 44.0 ug/dL, p=0.024). Ferritin, phosphorus, folic acid, vitamin B12, and zinc were also within normal limits. Magnesium was lower in patients with CD compared to UC (2.08 ± 0.15 vs. 2.15 ± 0.19, p=0.036 mg/dL). Vitamin D levels showed insufficient vitamin D in patients with UC and vitamin D deficiency (below 20 ng/mL) in patients with CD (20.1 ± 10.6 vs. 19.0 ± 9.9 ng/mL, p = 0.567) (Table 2). Conclusion Nutritional status of patients with IBD is favorable, and the lack of trace elements, specifically iron, magnesium, and vitamin D, and reduced skeletal muscle mass were observed to be prominent in patients with CD compared to UC.

P295 Early sonographic improvement predicts the middle-term efficacy of molecular-targeted medications for Ulcerative Colitis

Abstract Background Today molecular-targeted medications (MTMs) are widely used for ulcerative colitis (UC). Predicting the efficacy of MTMs early after induction remains a crucial clinical challenge. Intestinal ultrasound (IUS) is now considered a non-invasive, promising monitoring tool for UC. It can assess the disease activity of UC in the whole colon safely and repeatedly. Here, we hypothesized that over time IUS assessment can predict the MTM efficacy early, contribute to early clinical decision-making on whether to continue or switch MTMs, and reduce the burden of colonoscopy (CS) recommended to be scheduled at around 6 months after the induction. Methods We analyzed 44 patients who started an MTM for active UC, underwent IUS at baseline and 3 months, and took CS at 6 months after the induction. The clinical disease activity and endoscopic activity at 6 months were assessed with Lichtiger index (LI) and Mayo endoscopic subscore (MES), respectively. Clinical remission was defined as a LI ≤ 3. Endoscopic improvement (EI) was defined as a MES = 0 or 1. In addition to the assessment of sonographic findings, such as bowel wall thickness (BWT), bowel wall stratification including submucosa index (SMI), bowel wall flow with modified Limberg score (mLS), Milan Ultrasound Criteria (MUC), UC-IUS index (UII), Kyorin Ultrasound Criterion for UC (KUC-UC; BWT&amp;lt;3.8mm with SMI&amp;lt;50%) were evaluated. Results Patients who achieved steroid-free clinical remission (SFCR) showed better improvement in BWT, %BWT, and mLS in 3 months compared to those who did not achieve SFCR (p&amp;lt;0.01 for each). The improvement in MUC and UII was also observed in patients who achieved SFCR at 6 months (p&amp;lt;0.001 for both). In ROC analyses, the area under the curve for SFCR at 6 months was 0.80 with BWT, 0.80 with %BWT, 0.81 with mLS, 0.85 with MUC, and 0.85 with UII. Among the 44 patients, 7 patients achieved MUC≤ 6.2, estimating MES=0/1, at 3 months, and 6 out of 7 patients demonstrated EI at 6 months (positive predictive value [PPV]=87.5%). Meanwhile, 4 patients satisfied KUC-UC at 3 months and all of them achieved SFCR and EI at 6 months (PPV=100%). Conclusion Our study suggests that patients who achieved sonographic improvement in 3 months can continue an ongoing MTM therapy and that patients who demonstrated sonographic findings estimating EI at 3 months can postpone CS at 6 months.

P492 All intestinal ultrasound scores for ulcerative colitis (and IBUS-SAS) strongly correlate with endoscopic activity: a prospective study

Abstract Background Intestinal ultrasound (IUS) is gaining increasing acceptance as a reliable tool for tight monitoring of ulcerative colitis (UC). Although several IUS scores have been proposed, none has been formally implemented into official recommendations of international scientific societies. This study aims to compare the available IUS score for UC, in terms of correlation with endoscopic activity. Methods Patients with UC ≥ 18 years old undergoing partial or full colonoscopy between April and October 2023 were prospectively included. Endoscopic evaluation of at least the sigmoid colon was mandatory for inclusion, and patients with proctitis (Montreal E1) were excluded. Endoscopic activity was scored with both the Mayo Endoscopic Subscore (MES) and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and defined by MES ≥ 1 and UCEIS ≥ 2. IUS was performed within 4 weeks of endoscopy. The Milan Ultrasound Criteria (MUC, Allocca et al.), the UC-IUS score (Bots et al.), the US Score from Parente et al., and the score from Hata et al. were included in the analysis. Applicability of the US Score from Civitelli et al, an IUS score developed for paediatric patients, and the IBUS-SAS, an IUS score validated for Crohn’s disease, was also evaluated. The Spearman’s rank coefficient (rho = ρ) was used to perform correlations, while receiver operating characteristic (ROC) curves were compared with the Hanley &amp; McNeil method. Results Fifty-nine patients were included, of which 59.3% and 50.8% showed any endoscopic activity using the MES and the UCEIS, respectively. Detailed information about the population is reported in Table. All the evaluated IUS scores showed a significant positive correlation with endoscopic activity (p &amp;lt; 0.001), with the UC-IUS score and the US Score from Civitelli et al. outperforming the others both with MES (ρ = 0.745, ρ = 0.762) and UCEIS (ρ = 0.751, ρ = 0.769). The same scores showed the highest Areas Under the Curve (AUC) for detecting a MES ≥ 2 (UC-IUS: 0.841, 95%CI 0.722-0.923, p &amp;lt; 0.001; Civitelli et al.: 0.842, 95%CI 0.724-0.924, p &amp;lt; 0.001) [Figure]. The optimal cut-offs for detecting a MES ≥ 2 with both the MUC and the Civitelli score were similar to that proposed by the Authors (&amp;gt; 5.04 vs &amp;gt; 6.20 and &amp;gt; 2 vs &amp;gt; 1, respectively). Conclusion All the included IUS scores showed good correlation with endoscopic activity. The UC-IUS and the US Score from Civitelli et al. performed better than the others in detecting a MES ≥ 2 and might be suggested to monitor disease activity of UC and intervene early during disease relapse.

P281 The role of transabdominal ultrasound in evaluating Ulcerative Colitis disease activity and predicting treatment response

Abstract Background As a non-invasive, accurate, and feasible examination, transabdominal ultrasound（TAUS） is of great value in disease monitoring of ulcerative colitis. The cut-off for disease activity of 3.0 or 4.0 mm is often debated， and studies lacked assessment of treatment response. This study aimed to assess the diagnostic accuracy of TAUS in detecting disease activity in adult patients with UC using endoscopy as the reference standard and evaluate TAUS for treatment response in a longitudinal cohort. Methods This study prospectively consecutive adult patients with an established diagnosis of UC in the First Affiliated Hospital of Zhengzhou University between June 2022 and September 2023. The patients with moderate-to-severe disease activity at baseline should have follow-up endoscopic assessment after induction, with available corresponding TAUS. The primary outcome of this study was the difference in BWT in the descending colon(DC) or sigmoid colon(SC) for patients with and without segmental endoscopic response after treatment. Endoscopic remission was defined as MES=0-1 or UCEIS=0-1, and Endoscopic response as a decrease of MES ≥1 or a reduction of UCEIS ≥2. Results A total of 315 colon segments in 80 patients were included. 171 (54.3%) colorectal segments had endoscopic remission and 144(45.7%) were in endoscopic activity. The TAUS parameters correlated with the Mayo endoscopic sub-score with significant differences between patients in endoscopic remission and patients in endoscopic activity. And we found 3.45mm(AUROC 0.833;95%CI 0.789-0.878， P＜0.001) to be the cutoff for endoscopic remission with 78% sensitivity and 75% specificity. The multivariable analysis identified BWT， the Colour Doppler Signal(CDS), and the wall layer stratification as independent predictors for endoscopic activity（ P＜0.001、=0.004、=0.001）. BWT in the DC or SC was significantly lower in patients with endoscopic response than those without after treatment. A 28% decrease in BWT from baseline predicted endoscopic response [AUROC 0.743;95%CI 0.589-0.896， P=0.015] with 58% sensitivity and 93% specificity. Multivariable analysis among all the ultrasound parameters considered normal wall layer stratification at baseline as the only independent predictor of endoscopic response at reassessment (odds ratio [OR]23.334, 95% CI 2.257-241.219; p = 0.008). Conclusion TAUS, importantly BWT, CDS, and wall layer stratification as the crucial parameters, is highly accurate in detecting disease activity and treatment response when evaluated against endoscopic outcomes. Normal intestinal wall stratification at baseline predicts long-term endoscopic response.

P066 Serum amyloid A – A Novel Biomarker of Ulcerative Colitis Disease Activity

Abstract Background Despite recent advancements in the treatment of ulcerative colitis (UC), a substantial number of patients fail to achieve long-term remission. Persistent histological activity has been linked with poorer treatment outcomes. Histological remission is now an accepted treatment target; however there remains significant variability in the interpretation of UC histology. As such, there is a need for novel biomarker identification to aid assessment and ultimately predict disease relapse. Serum amyloid A (SAA) is an acute-phase protein, of which serum levels have shown promise as a biomarker in IBD1. This study aims to explore the utility of SAA levels in UC colonic tissue as a diagnostic biomarker for disease activity and progression. Methods Two cohorts were prospectively recruited, including healthy controls and UC patients. Sigmoid biopsies were collected and tissue explants generated. Tissue-conditioned media from these explants was collected and secreted SAA quantified using 54 V-plex ELISA. Demographic information, disease characteristics, endoscopic Mayo scores and disease progression were documented. Endoscopic remission was defined as a Mayo endoscopic sub-score ≤1. Disease progression was defined as the requirement for corticosteroid therapy, UC-related hospitalisation, UC-related surgery or the introduction of a new immunomodulatory agent in follow-up period. P values &amp;lt;0.05 were considered significant in analyses. Results The two cohorts included 11 healthy controls and 16 UC patients (endoscopic remission n=6). Active UC patients demonstrated significantly higher SAA concentrations than healthy controls (p=0.0013) and those in endoscopic remission (p=0.02). There was no significant difference in SAA concentrations between healthy controls and UC patients in remission (p=NS). UC patients in the lowest SAA concentration quartile had a significantly longer time to disease progression (p=0.0462) (Figure 1). Conclusion Quantification of SAA secretion in IBD ex-plants has potential as a biomarker of UC activity and progression. Further investigation of SAA as a biomarker in IBD is warranted.