Disease Severity In Ulcerative Colitis Research Articles

Gut colonization with antibiotic resistance Escherichia coli pathobionts leads to disease severity in ulcerative colitis.

Escherichia coli is a Gram-negative commensal of human gut. Surprisingly, the role of E. coli in the pathogenesis of ulcerative colitis (UC) has not been explored till date. Human gut microbiota composition and meta-gut resistome was evaluated using metagenomics. Antibiotic susceptibility of E. coli isolates against different class of antibiotics was investigated. Further, the genome sequence analysis of E. coli isolates was performed to get insight into the antimicrobial resistance (AMR) mechanism and virulence factors. Gut proteome of UC and non-UC was examined to understand the effect of resistant bacteria on host physiology. In UC patients, meta-gut resistome was found to be dominated by AMR genes (829) compared to healthy control (HC) [518]. Metagenome study revealed higher prevalence of AMR genes in rural population (378 in HC; 607 in UC) compared to urban (340 in HC; 578 in UC). Approximately, 40% of all E. coli isolates were multi-drug resistant with higher prevalence in UC (43.75%) compared to HC (33.33%). Up-regulated expression of antimicrobial human proteins (lactotransferrin, azurocidin, cathepsin G, neutrophil elastase, and neutrophil defensin 3) and immuneproteins (Protein S100-A9 and Protein S100-A8) suggest microbial infection in UC gut. In addition to the conventional culturomics method, multi-omics strategy provides deeper insights into the disease etiology, emergence of pathobionts, andits role in the disruption of the healthy gut environment in UC patients.

Clinical practice and outcome of patients with elderly-onset ulcerative colitis: Insights from a nationwide claims database study in Japan.

The number of older patients with ulcerative colitis is increasing; however, limited data exist regarding the differences between elderly- and non-elderly-onset ulcerative colitis. We aimed to compare the clinical practice and course of elderly-onset ulcerative colitis with those of non-elderly-onset ulcerative colitis. We selected older patients with ulcerative colitis and divided them into the elderly- and non-elderly-onset ulcerative colitis groups according to their age at onset. We compared the cumulative systemic steroid-free, molecular targeting drug-free, and surgery-free rates between the two groups. We performed a multivariate analysis to identify the clinical factors related to systemic steroid administration, the use of molecular targeting drugs, surgery, and death. We collected data of 2669 and 277 elderly and non-elderly-onset ulcerative colitis patients, respectively. The cumulative systemic steroid-free rate of elderly-onset ulcerative colitis was significantly lower than that of non-elderly-onset ulcerative colitis. However, no difference was observed in the cumulative molecular targeting drugs and surgery-free rates between the two groups. Elderly-onset ulcerative colitis significantly increased the risk of systemic steroid administration and death but not the use of molecular targeting drugs and surgery. The disease severity of ulcerative colitis and clinical practice may not differ between the elderly- and non-elderly-onset groups. However, elderly-onset ulcerative colitis was associated with increased mortality risk. Thus, we need to pay attention to the patients' condition and appropriate timing of surgery for patients with elderly-onset ulcerative colitis.

Is there any association between dietary FODMAP score and disease severity in patients with ulcerative colitis?

IntroductionWe hypothesized that low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet may associated with the disease severity of ulcerative colitis (UC). So, this cross-sectional study was undertaken to assess the association between FODMAP score and UC severity. MethodsIn this study, 158 patients with UC were enrolled. The disease severity was designated using the Mayo Clinic score. The diet relation information was obtained using the 160-item food frequency questionnaire. For calculating the FODMAP score, the consumption of all food items was converted to a gram per day and multiplied by the FODMAP factor. The FODMAP factor was obtained from the application developed by the University of Monash, Melbourne, Australia. An association between disease severity (dependent factor) and FODMAP score tertiles (independent factors) was conducted by a logistic regression adjusted to different covariates. ResultsIn the present study, the age range of participants was 18-64 years old, and 46.2% of patients had moderate or severe disease activity. There were significant differences in gender, body mass index, and supplement use across different tertiles of FODMAP score. There was no significant association between the FODMAP score tertiles and disease severity in the crude model and adjusted models. ConclusionThe results of the present study showed that there was no significant association between the FODMAP score and UC severity. However, considering the limitations of the study, more studies with prospective and interventional designs and using more accurate methods of dietary assessments are needed to confirm these preliminary results.

Is Helicobacter pylori Infection Associated With Ulcerative Colitis Activity?

Objectives: Epidemiological studies have shown an inverse association between <i>Helicobacter pylori</i> infection and ulcerative colitis (UC). In this study, we investigated the protective effects of H. pylori infection on the severity of UC.Methods: This single-center study included 316 patients with newly diagnosed UC based on findings of colonoscopy and upper endoscopy for H. pylori evaluation between January 1994 and December 2015. Patients’ medical records were retrospectively reviewed, and severity of UC was assessed based on endoscopic findings, clinical symptoms, treatment regimens, and Mayo scores.Results: The prevalence of <i>H. pylori</i> infection in patients with UC was 74/316 (23.4%). Based on upper endoscopic findings, the percentage of patients with duodenal ulcers was significantly higher in the H. pylori positive group than that in the <i>H. pylori</i> negative group (27.0% vs. 11.6%, <i>p</i>=0.022). Disease extent and endoscopic severity showed no significant intergroup difference (<i>p</i>=0.765 and <i>p</i>=0.803, respectively). Endoscopic severity was unaffected by the <i>H. pylori</i> infection status, based on the extent of endoscopically documented disease and endoscopic findings. Furthermore, UC-related symptom severity assessed on the basis of stool frequency, rectal bleeding severity, and rate of admission necessitated by UC aggravation was not associated with <i>H. pylori</i> infection (<i>p</i>=0.185, 0.144, and 0.182, respectively). Use of steroids as induction therapy for severe UC did not differ with regard to <i>H. pylori</i> infection (<i>p</i>=0.327). No intergroup difference was observed in disease severity of UC classified using the Mayo score (<i>p</i>=0.323).Conclusions: <i>H. pylori</i> infection was detected in approximately 25.0% of patients with UC. However, the <i>H. pylori</i> infection status was not associated with the severity of UC based on endoscopic disease activity, patients’ symptoms, steroid use, or the Mayo clinic score.

A268 1 YEAR FOLLOW-UP OF PEDIATRIC ULCERATIVE COLITIS USING INTESTINAL ULTRASOUND

Abstract Background Intestinal ultrasound (IUS) is an emerging tool that offers a non-invasive method for monitoring inflammatory bowel disease in pediatric patients, with increasing popularity worldwide. Assessment of IUS for monitoring pediatric Ulcerative Colitis (UC) has been previously limited to small samples of patients with no long-term follow up. Aims This project aims to utilize intestinal ultrasound assessments obtained at routine time points to determine changes in IUS parameters within 12 months of study enrollment in newly diagnosed children with UC, and their relationship to biochemical markers, clinical assessments, and endoscopic findings. Methods Pediatric patients with suspected ulcerative colitis were prospectively enrolled through the Edmonton Pediatric IBD Clinic. Participants underwent IUS, clinical assessments, bloodwork for biomarkers, and fecal calprotectin (FCP) testing at baseline, 1-, 3-, 6-, and 12-month visits, as well as endoscopy at baseline and 6-12 months. In each IUS assessment, the bowel wall thickness (BWT), presence of hyperemia, abnormal haustrations, and fat wrapping was determined in 4 bowel segments (right, transverse, descending, and sigmoid colon). The Pediatric Ulcerative Colitis Activity Index (PUCAI) scores and Ulcerative Colitis Intestinal Ultrasound Scores (UC-IUS) were calculated at each visit. Results 42 patients (55% male) were included. Median UC-IUS total scores and BWT alone improved in all bowel segments over the study period. For the most affected bowel segment for all patients, median percent reduction of BWT was 39.6%, 34.2%, 33.7%, and 42.5%, at the 1-, 3-, 6-, and 12-month assessment respectively. The biggest decrease in UC-IUS scores and BWT occurred with the initiation of therapy between baseline and 1-month. UC-IUS scores significantly correlated with endoscopy at 12-months, clinical assessments at all time points, and biochemical markers of disease at all time points over the 12-month study period (pampersand:003C0.05). BWT measurement alone also had significant correlation with endoscopy at 12 months; clinical assessment at 1-, 3-, and 6-months; and with biochemical markers at every time point (pampersand:003C0.05). Patients with inflammatory bowel markers (indicated by elevated FCP (ampersand:003E250)) at 12-months were found to have significantly thicker BWT and UC-IUS scores at 3- and 6-months. Conclusions BWT and UC-IUS performed well in pediatric patients with newly-diagnosed UC, with UC-IUS scores and BWT measurements alone correlating significantly with endoscopic, clinical, and biochemical disease activity over the 12-month study period. BWT alone performed similarly to total UC-IUS scores. This data suggests that IUS can offer a non-invasive method to monitor long-term pediatric UC disease severity. Funding Agencies TRIANGLE, WCHRI, Stollery Children's Hospital Foundation.

BREASTFEEDING STATUS AND DISEASE SEVERITY IN PEDIATRIC PATIENTS WITH ULCERATIVE COLITIS: AN EXPLORATORY RETROSPECTIVE COHORT STUDY

Abstract OBJECTIVE While the protective effect of being breastfed on the development of ulcerative colitis has been well established, it is not known if being breastfed decreases colectomy rate and disease severity for pediatric patients. This work is designed to better understand the connection between breastfeeding status and disease severity of ulcerative colitis among pediatric patients. METHODS This exploratory retrospective cohort study analyzed the clinical and laboratory data of patients at Boston Children’s Hospital enrolled in a data registry and biorepository since 2012. Data was collected from charts and analyzed to determine if there is a significant difference in colectomy rate, pediatric ulcerative colitis activity index (PUCAI) score, ESR, or CRP, between not breastfed (n=56), breastfed (n=39), and mixed breastfed patients (n=31). Breastfed patients are defined as patients who were exclusively breastfed for greater than or equal to three months. Patients who were never breastfed were considered not breastfed. Patients who were exclusively breastfed for less than three months or received a mix of formula and breastfeeding were considered mixed breastfed. Statistical analysis of the groups was performed using a one-way ANOVA. RESULTS At disease diagnosis, the average PUCAI score of the not breastfed group (32.4) was significantly higher than the exclusively breastfed group (18.4) (p value = 0.0189). No significant difference was detected in the average PUCAI score of the mixed breastfed group (34.1) compared to the not breastfed group (32.4). Significant differences in the colectomy rate between all three groups were not detected, and likewise we did not find significant differences in markers of disease severity including ESR, CRP, and hemoglobin at diagnostic visit between groups. CONCLUSION These results suggest that children with ulcerative colitis who were exclusively breastfed have a lower average PUCAI score at the time of diagnosis than those who were not breastfed. Further investigation with larger data sets may be necessary to determine other benefits of exclusive breastfeeding in pediatric ulcerative colitis patients.

P098 The Endoscopic Severity Score Map (ESSM): An Artificial Intelligence scoring system providing accurate, objective and localised measurements of endoscopic disease severity in ulcerative colitis

Abstract Background Commonly used scoring schemes as the Mayo Endoscopic Subscore (MES) account for disease severity only at specific (i.e., the worst) segments and do not capture disease extent. However, for an accurate assessment of disease severity in patients with ulcerative colitis (UC), the measure of the precise extent of disease activity is necessary. Alternative systems that include disease extent have been proposed (Balint 2018), but their implementation is prohibited by the time and cost constraints of comprehensively scoring each location along the entire colon. Here, we present the Endoscopic Severity Score Map (ESSM), a scoring system based on Artificial Intelligence, capable of providing an assessment of disease severity and extent in UC in a fully automated manner. Methods The ESSM consists of 3 main elements (Fig. 1): 1) a quality algorithm which selects readable frames from a colonoscopy video, 2) a scoring system which assigns an MES to each readable frame (Gutierrez Becker 2020) and 3) a camera localisation algorithm that assigns each frame to an anatomical location within the colon (Yao 2022). The ESSM was trained and tested using 4,306 sigmoidoscopy videos from phase III Etrolizumab clinical trials (Hickory NCT02100696, Laurel NCT02165215, Hibiscus I NCT02163759, Hibiscus II NCT02171429 and Gardenia NCT02136069). Results We evaluate the performance of the ESSM by first assessing the agreement of scoring as compared to centrally read MES. The agreement between central reading and the ESSM at the colon section level was high (quadratic-weighted kappa k=0.81; Tab. 1). This was comparable to the agreement between central and local reading (k=0.84), suggesting that the ESSM shows levels of inter-rater variability comparable to experienced readers. Finally, we found correlations between the average ESSM at all anatomical locations and other disease activity markers to be moderate to high: faecal calprotectin rs=0.24, CRP rs=0.29, stool frequency rs=0.49, rectal bleeding rs=0.43 and physician global assessment rs=0.47 (Tab. 1). Conclusion Here, we introduced the ESSM, a fully-automated AI-based scoring system that enables accurate, objective and localised assessment of disease severity in UC. In brief, we show that the ESSM compares well with central reading (at the colon section level) and has clinical relevance when compared to other markers of disease activity. This tentatively suggests that the ESSM has the potential to augment the current way of assessing disease severity, both in clinical trials and everyday clinical practice.

P816 Baseline disease severity of patients with Ulcerative Colitis influences rapid symptom relief under filgotinib treatment: post hoc analysis of the phase 2b/3 SELECTION study

Abstract Background Filgotinib (FIL) is an oral, once-daily, Janus kinase 1 preferential inhibitor approved in Europe and Japan for the treatment of ulcerative colitis (UC). A recent analysis of SELECTION trial data (NCT02914522) showed rapid and sustained improvements in UC symptoms with FIL 200 mg (FIL200) treatment in patients with moderate-to-severe UC.1 Here we assess symptomatic remission rates over time with FIL200 induction treatment according to baseline UC disease severity (partial Mayo Clinic Score [pMCS]). Methods SELECTION was a phase 2b/3 randomized, double-blind, placebo-controlled study. Patients aged 18–75 years were randomized (2:2:1) to receive FIL200, FIL 100 mg or placebo once daily for 11 weeks in induction study A (biologic-naive patients) or induction study B (biologic-experienced patients). In this post hoc analysis, proportions of patients with symptomatic remission (Mayo rectal bleeding sub-score of 0 and Mayo stool frequency sub-score of ≤ 1), from days 2 to 15 and weeks 2 to 10 of the induction study, were analysed at each timepoint by baseline pMCS (pMCS ≥7 and pMCS <7 [cut-off previously used for severe and moderate disease, respectively]2). Symptomatic remission rates were compared between the pMCS ≥7 and pMCS <7 groups within the FIL200 and placebo arms using a Cochran–Mantel–Haenszel test adjusted by study randomization stratification factors. Nominal p values <0.05 were considered statistically significant. Results At day 2, symptomatic remission rates with FIL200 treatment were significantly higher in patients with baseline pMCS <7 than in those with baseline pMCS ≥7 (8.4% vs 1.1%, p=0.009 [induction study A]; 8.8% vs 0.7%, p=0.004 [induction study B]) (Figure A and B). From days 2 to 15, symptomatic remission rates increased in both groups and, except for day 7 for induction study A and day 9 for induction study B, continued to be significantly higher in those with baseline pMCS <7. From week 2, symptomatic remission rates with FIL200 treatment generally continued to increase in both pMCS ≥7 and pMCS <7 groups (Figure C and D). By week 10, symptomatic remission rates with FIL200 treatment were no longer significantly different between those with baseline pMCS <7 and those with baseline pMCS ≥7 (54.8% vs 43.3%, p=0.124 [induction study A]; 39.5% vs 26.4%, p=0.099 [induction study B]). Conclusion Symptomatic response to FIL200 occurs more rapidly in patients with lower UC disease severity than in those with higher UC disease severity. However, converging response rates over 10 weeks of treatment leads to symptomatic remission regardless of baseline UC disease severity.

P299 Ulcerative Colitis Severity Assessment through Abdominal Ultrasonography: A Diagnostic Accuracy Meta-analysis

Abstract Background Ulcerative colitis, a prevalent form of inflammatory bowel disease, necessitates a precise evaluation of disease severity. While effective, traditional diagnostic methods like colonoscopy are invasive and uncomfortable for patients. Abdominal ultrasonography offers a non-invasive alternative for this assessment, but its differential accuracy in evaluating disease severity in the right and left colon is not fully explored.This study aims to assess the diagnostic accuracy of abdominal ultrasonography in determining the severity of ulcerative colitis, focusing on its performance in the right and left colon. Methods A systematic review was conducted in PubMed, EMBASE, and the Cochrane Library, targeting studies up to June 2023. The selection criteria included studies that used abdominal ultrasonography for ulcerative colitis severity assessment, compared against histopathology or combined clinical, endoscopic, and radiological findings. Data analysis was performed using R software (version 4.0.3) with the mada package. This analysis focused on calculating sensitivity, specificity, diagnostic odds ratio, and positive and negative Likelihood Ratios for both the right and left colon, each with a 95% Confidence Interval. Results The search identified 5 studies with a total of 383 ulcerative colitis patients. In the right colon, the pooled sensitivity was 73.7% (95% CI, 57.6-85.2%, I2=0%), and specificity was 99.5% (95% CI, 1.6-100%, I2=0%). The diagnostic odds ratio was extremely high at 560.1 (95% CI, 0.04-6966551), with a positive Likelihood Ratio of 148.14 (95% CI, 0.01-1713586.1) and a negative Likelihood Ratio of 0.26 (95% CI, 0.15-0.45). In the left colon, sensitivity was higher at 93.7% (95% CI, 87.2-97%, I2=49.1%) with a specificity of 73.3% (95% CI, 41.8-91.3%, I2=70.9%). The diagnostic odds ratio for the left colon was 40.96 (95% CI, 8.67-193.62), with a positive Likelihood Ratio of 3.51 (95% CI, 1.31-9.42) and a negative Likelihood Ratio of 0.08 (95% CI, 0.04-0.19). Conclusion Abdominal ultrasonography shows promising results in assessing disease severity in ulcerative colitis, particularly in the left colon. The high specificity in the right colon is notable, but the wide confidence intervals suggest caution in interpretation, likely due to the small sample sizes and study variability. The left colon's more consistent and reliable performance indicates its suitability for routine clinical use in this region. This study highlights the need for further research with larger patient cohorts and standardized methodologies to solidify these findings and optimize ultrasonography’s role in ulcerative colitis management.

P417 1 year follow-up of pediatric ulcerative colitis using intestinal ultrasound

Abstract Background Intestinal ultrasound (IUS) is an emerging tool that offers a non-invasive method for monitoring inflammatory bowel disease in pediatric patients, with increasing popularity worldwide. Assessment of IUS for monitoring pediatric Ulcerative Colitis (UC) has been limited to small samples of patients with no long-term follow up. Our aim is to utilize intestinal ultrasound assessments obtained at routine time points to determine changes in IUS parameters within 12 months of study enrollment in newly diagnosed children with UC, and their relationship to biochemical markers, clinical assessments, and endoscopic findings. Methods Pediatric patients with suspected ulcerative colitis were prospectively enrolled through the Edmonton Pediatric IBD Clinic. Participants underwent IUS, clinical assessments, bloodwork for biomarkers, and fecal calprotectin (FCP) testing at baseline, 1-, 3-, 6-, and 12-month visits, as well as endoscopy at baseline and 6-12 months. In each IUS assessment, the bowel wall thickness (BWT), presence of hyperemia, abnormal haustrations, and fat wrapping was determined in 4 bowel segments (right, transverse, descending, and sigmoid colon). The Pediatric Ulcerative Colitis Activity Index (PUCAI) scores and Ulcerative Colitis Intestinal Ultrasound Scores (UC-IUS) were calculated at each visit. Results 42 patients (55% male) were included. Median UC-IUS total scores and BWT alone improved in all bowel segments over the study period. For the most affected bowel segment for all patients, median percent reduction of BWT was 39.6%, 34.2%, 33.7%, and 42.5%, at the 1-, 3-, 6-, and 12-month assessment respectively. The biggest decrease in UC-IUS scores and BWT occurred with the initiation of therapy between baseline and 1-month. UC-IUS scores significantly correlated with endoscopy at 12-months, clinical assessments at all time points, and biochemical markers of disease at all time points over the 12-month study period (p<0.05). BWT measurement alone also had significant correlation with endoscopy at 12 months; clinical assessment at 1-, 3-, and 6-months; and with biochemical markers at every time point (p<0.05). Patients with inflammatory bowel markers (indicated by elevated FCP (>250)) at 12-months were found to have significantly thicker BWT and UC-IUS scores at 3- and 6-months. Conclusion BWT and UC-IUS performed well in pediatric patients with newly-diagnosed UC, with UC-IUS scores and BWT measurements alone correlating significantly with endoscopic, clinical, and biochemical disease activity over the 12-month study period. BWT alone performed similarly to total UC-IUS scores. This data suggests that IUS can offer a non-invasive method to monitor long-term pediatric UC disease severity.

Revisiting the Role of Valeric Acid in Manipulating Ulcerative Colitis.

Ulcerative colitis (UC) is characterized by a complicated interaction between mucosal inflammation, epithelial dysfunction, abnormal activation of innate immune responses, and gut microbiota dysbiosis. Though valeric acid (VA), one type of short-chain fatty acids (SCFAs), has been identified in other inflammatory disorders and cancer development, the pathological role of VA and underlying mechanism of VA in UC remain under further investigation. Studies of human clinical specimens and experimental colitis models were conducted to confirm the pathological manifestations of the level of SCFAs from human fecal samples and murine colonic homogenates. Valeric acid-intervened murine colitis and a macrophage adoptive transfer were applied to identify the underlying mechanisms. In line with gut microbiota dysfunction in UC, alteration of SCFAs from gut microbes were identified in human UC patients and dextran sodium sulfate -induced murine colitis models. Notably, VA was consistently negatively related to the disease severity of UC, the population of monocytes, and the level of interluekin-6. Moreover, VA treatment showed direct suppressive effects on lipopolysaccharides (LPS)-activated human peripheral blood mononuclear cells and murine macrophages in the dependent manner of upregulation of GPR41 and GPR43. Therapeutically, replenishment of VA or adoptive transfer with VA-modulated macrophages showed resistance to dextran sodium sulfate-driven murine colitis though modulating the production of inflammatory cytokine interleukin-6. In summary, the research uncovered the pathological role of VA in modulating the activation of macrophages in UC and suggested that VA might be a potential effective agent for UC patients.

Correlation of Blood and Intestinal Mucosa miR-34a Expressions with Disease Severity in Ulcerative Colitis Patients.

miR-34a has been implicated in many autoimmune diseases and gastrointestinal diseases. However, the expression of miR-34 in ulcerative colitis (UC) patients were not fully studied. This study was performed to in-vestigate the association of blood and intestinal tissue miR-34a expression of patients with disease severity in UC patients. Our study enrolled 82 patients with UC and 80 age- and gender- matched healthy individuals. Blood miR-34a expressions were detected using reverse transcription-polymerase chain reaction (RT-PCR). Local intestinal miR-34a, STAT3 mRNA and IL-23 mRNA expressions were also detected in the lesioned area and adjacent non-affected intestinal tissue in patients. Disease severity of UC was assessed by Mayo score. The diagnostic value of both blood and local miR-34a expression for UC patients was assessed by receiver operating characteristic (ROC) curve. Blood miR-34a was increased in UC patients in contrast with healthy individuals with statistical significance. In UC patients, local intestinal miR-34a expressions were markedly upregulated compared to adjacent non-affected intestinal tissue. Local intestinal miR-34a expressions were positively correlated with STAT3 mRNA and IL-23 mNRA. Both blood and local miR-34a expressions were significantly and positively related to Mayo scores. ROC curve analysis indicated that both blood and local miR-34a expressions may act as decent marker for Mayo grade. Blood and intestinal tissue miR-34a expressions are correlated with disease severity in UC patients. Both blood and intestinal tissue miR-34a expressions may serve as potential diagnostic and prognostic makers for UC. Therapeutic methods targeting miR-34a may act as potential ways for UC treatment.

The Role of Akkermansia muciniphila and Faecalibacterium prausnitzii in the Pathogenesis of Ulcerative Colitis and Crohn's Disease.

Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases with uncertain etiology. We aimed to determine the amounts of Akkermansia muciniphila and Faecalibacterium prausnitzii in the intestinal microbiota of these patients and to correlate their amounts with blood IL-8, IL-10, and IL-12 cytokine levels. Thirty UC, 30 CDs, and 46 healthy controls were included. IL-8, IL-10, and IL-12 levels of blood samples were analyzed by ELISA. The amounts of Akkermansia muciniphila and Faecalibacterium prausnitzii were determined by the LightCycler 480 qPCR system. F. prausnitzii, A. muciniphila, IL-10, and IL-12 decreased in patient groups, while IL-8 decreased in UC but increased in CD. A significant difference was detected between the patient and control groups in terms of F. prausnitzii, A. muciniphila, and IL-8, but not for others. The amount of F. prausnitzii was correlated with IL-8 and IL-10 in UC and with IL-10 in CD patients. The decrease in the amount of F. prausnitzii was associated with the increase in UC disease severity. A. muciniphila and F. prausnitzii were detected in lower amounts in both diseases. F. prausnitzii decreased more with the severity of UC, suggesting that these bacteria may have complex roles in their etiopathogenesis.

The ulcerative colitis endoscopic index of severity score is superior to reflecting long-term prognosis in ulcerative colitis patients treated with vedolizumab.

The scoring systems commonly used to assess endoscopic disease severity of ulcerative colitis (UC) in clinical research and practice include the Mayo endoscopic score (MES), ulcerative colitis endoscopic severity index (UCEIS), and degree of ulcerative colitis burden of luminal inflammation (DUBLIN). We aimed to assess and compare the predictive efficacy of the MES, DUBLIN score and UCEIS score for prognosis in UC patients treated with vedolizumab (VDZ). Seventy-four UC patients who treated with VDZ from September 2021 to February 2023 were retrospectively enrolled. We used the MES, DUBLIN and UCEIS score to evaluate endoscopic findings. The predictive capability of these 3 scores for surgery or therapeutic escalation was assessed using the receiver operating characteristic curve. The mean MES, DUBLIN and UCEIS score significantly improved from 2.83 ± 0.38, 7.80 ± 1.82 and 6.24 ± 1.51 to 2.07 ± 0.88, 5.57 ± 2.68, and 3.72 ± 2.12, respectively (P < .001). Lower pre-therapeutic UCEIS scores were associated with favorable short-term outcomes. Importantly, the post-therapeutic UCEIS score showed the best predictive capability with an area under curve of 0.871 (95% confidence interval: 0.767-0.976), specificity of 0.654, sensitivity of 0.900, and cutoff value of 3.5. A UCEIS score of ≥ 4 after treatment was correlated with surgical operation or treatment escalation. The UCEIS score is superior to the MES and DUBLIN score in reflecting short-term outcomes and long-term prognosis in UC patients treated with VDZ, and clinical remission could be defined as a UCEIS score ≤ 3.

Systemic immune-inflammation index as a potential biomarker to monitor ulcerative colitis

Objective The treat-to-target strategy is recommended by Selecting Therapeutic Targets in Inflammatory Bowel Disease II (STRIDE-II) for treating ulcerative colitis (UC), and monitoring remission status is crucial during this management. The systemic immune-inflammation index (SII), defined as platelet * neutrophil/lymphocyte, is a complete blood count-based index reflecting the balance of immune and inflammatory status. This study aims to investigate the feasibility of SII for diagnosing UC and monitoring UC disease activity. Methods This study retrospectively analyzed patients with UC and controls. Relationships between SII and Mayo clinical score, Mayo Endoscopic Score (MES), and Nancy Histological Index (NHI) were evaluated. Results 167 patients with UC and 106 controls were included. SII significantly increased in patients with UC and was closely correlated with the Mayo clinical score, MES, and NHI. SII diagnosed UC with a cut-off value of 619.1 × 109/L (area under the curve = 0.861, p < 0.0001, sensitivity 79.64%, specificity 77.36%), evaluated clinical remission status with a cut-off value of 1068 × 109/L (area under the curve = 0.691, p < 0.05, sensitivity 55.71%, specificity 81.48%), endoscopic improvement with a cut-off value of 981.3 × 109/L (area under the curve = 0.819, p < 0.0001, sensitivity 65.22%, specificity 89.66%), and histological healing with a cut-off value of 689.3 × 109/L (area under the curve = 0.898, p < 0.0001, sensitivity 88.89%, specificity 95.83%). Conclusion SII is a potential biomarker for diagnosing UC and monitoring UC disease severity, especially in evaluating mucosal and histological healing during the long-term management in treat-to-target strategy. However, further research is needed to confirm its usefulness and optimize its clinical application.

The Communicating Needs and Features of IBD Experiences (CONFIDE) Study: US and European Patient and Health Care Professional Perceptions of the Experience and Impact of Symptoms of Moderate-to-Severe Ulcerative Colitis.

The Communicating Needs and Features of IBD Experiences (CONFIDE) study aimed to evaluate the experience and impact of ulcerative colitis (UC) symptoms on patients' lives and elucidate gaps in communication between patients and health care professionals (HCPs). Online, quantitative, cross-sectional surveys of patients with moderate-to-severe UC and HCPs responsible for making prescribing decisions were conducted in the United States (US) and Europe. UC disease severity was defined by treatment, steroid use, and/or hospitalization history. Surveys were completed by 200 US and 556 European patients and 200 US and 503 European HCPs. The most common UC symptoms experienced in the preceding month were diarrhea, bowel urgency, and increased stool frequency. Many patients (45.0% of US patients, 37.0% of European patients) reported wearing diapers/pads/protection at least once a week in the past 3 months due to fear/anticipation of fecal urge incontinence. The top reasons for declining participation in social events, work/school, and sports/exercise were due to bowel urgency and fear of fecal urge incontinence. HCPs ranked diarrhea, blood in stool, and increased stool frequency as the most common symptoms. While over half HCPs ranked bowel urgency as a top symptom affecting patients' lives, less than a quarter ranked it in the top 3 most impactful on treatment decisions. Similar disparities exist between patient and HCP perceptions in the United States and Europe on the experience and impact of UC symptoms. Bowel urgency has a substantial and similar impact on US and European patients, is underappreciated by HCPs, and should be addressed during routine appointments.

Clinical utility of colon capsule endoscopy: a moving target?

The purpose of this article is to provide an overview of white light colon capsule endoscopy's current clinical application, concentrating on its most recent developments. Second-generation colon capsule endoscopy (CCE2) is approved by the FDA for use as an adjunctive test in patients with incomplete colonoscopy and within Europe in patients at average risk, those with incomplete colonoscopies or those unwilling to undergo conventional colonoscopies. Since the publication of European Society of GI Endoscopy guidelines on the use of CCE, there has been a significant increase in comparative studies on the diagnostic yield of CCE. This paper discusses CCE2 in further detail. It explains newly developed colon capsule system and the current status on the use of CCE, it also provides a comprehensive summary of systematic reviews on the implementation of CCE in colorectal cancer screening from a methodological perspective. Patients with ulcerative colitis can benefit from CCE2 in terms of assessing mucosal inflammation. As part of this review, performance of CCE2 for assessing disease severity in ulcerative colitis is compared with colonoscopy. Finally, an assessment if CCE can become a cost-effective clinical service overall.

Steroid Resistance/Dependence Might Be an Alarming Feature for Cytomegalovirus Infection Among Ulcerative Colitis Patients With Increased Disease Activity.

Background/Aims This study aimed to determine the prevalence of cytomegalovirus (CMV) infection among patients with moderate to severe active ulcerative colitis (UC) and to determine the risk factors for CMV infection according to the demographic features of these patients. Patients/Methods A total of 183 patients with severe or moderate active UC were enrolled in the study after retrospective analysis. The disease severity of UC was determined according to the Mayo Score. CMV infection was investigated by real-time quantitative polymerase chain reaction (PCR) and the immunohistochemical (IHC) staining method in colonic mucosal biopsies. Results CMV infection was diagnosed in 33.9% of patients with UC. UC patients diagnosed with CMV infection had significantly higher Mayo Score levels (9.68 vs 8.56 and p=0.001). The long-term presence of UC disease, steroid, azathioprine (AZA), and anti-tumor necrosis factor-alpha (anti-TNF-alpha) usage increased the risk of CMV infection (p=0.001 and odds ratio=1.168; p=0.001 and odds ratio=2.967; p=0.004 and odds ratio=2.953; p=0.003 and odds ratio=3.861, respectively). CMV infection increases the risk of developing steroid resistance or dependency (p=0.002 and odds ratio=3.147; p=0.002 and odds ratio=5.085, respectively). Post-treatment clinical remission and mucosal healing rates were higher in CMV-negative patients than in CMV-positive patients (99.2% vs 91.9%, p=0.018 and 86.8% vs 70.9%, p=0.015). A higher rate of need for colectomy had been found in patients with CMV infection (5 patients vs 1 patient; p=0.034 and odds ratio=10.526). Conclusions The presence of CMV infection increases the severity of the diseaseand worsens clinical outcomes, leading to adverse treatment outcomes. CMV infection increases the requirement for colectomy. The presence of steroids, immunosuppressives such as AZA, and anti-TNF-alpha usage increases the occurrence of CMV infection. CMV infection should be suspected in patients with moderate to severe UC activity.

Fibromodulin Ablation Exacerbates the Severity of Acute Colitis.

IntroductionEpidemiological studies have associated pigment production with protection against certain human diseases. In contrast to African Americans, European descendants are more likely to suffer from angiogenesis-dependent and inflammatory diseases, such as wet age-related macular degeneration (ARMD) and ulcerative colitis (UC), respectively.MethodsIn a mouse model of dextran sulfate sodium (DSS)-induced acute colitis, the effect of fibromodulin (FMOD) depletion was examined on colitis severity.ResultsIn this study, albino mice that produce high levels of FMOD developed less severe acute colitis compared with mice lacking in FMOD as assessed by clinical symptoms and histopathological changes. FMOD depletion affected the expression of tight junction proteins, contributing to the destruction of the epithelial barrier. Furthermore, this study revealed a stronger inflammatory response after DSS treatment in the absence of FMOD, where FMOD depletion led to an increase in activated T cells, plasmacytoid dendritic cells (pDCs), and type I interferon (IFN) production.DiscussionThese findings point to FMOD as a potential biomarker of disease severity in UC among light-skinned individuals of European descent.

Ülseratif Kolitli Hastalarda Netrin-1 Düzeyinin Klinik ve Hastalık Aktivitesini Değerlendirmedeki Rolü ve TNF-alfa, IL-6 ile İlişkisi

Objective: We investigated the importance of netrin-1 levels in Ulcerative Colitis (UC) in clinical activity of the disease, and its association with other proinflammatory cytokines IL-6 and TNF-alpha.Materials and Methods: This study was a case-control study and included 67 patients with UC (36 activated, 31 in remission) and 50 healthy controls. UC patients were divided into mild activation (n=21), moderate activation (n= 6) and severe activation (n= 9) groups according to the "Truelove Witts clinical activity index". 31 asymptomatic patients were considered to be in remission. Netrin-1, IL-6 and TNF-alpha measurements in plasma samples were made using ELISA assay kit.Results: Between the patient group and the control group; there was a statistically significant difference between netrin-1, IL-6, TNF-alpha, (p&amp;lt;0.05 for all). The plasma netrin-1 mean of UC with severe activation groupwas statistically significantly higher than that of the mild activation, remission group and control group (p&amp;lt;0.05). Plasma netrin-1 mean of UC with modarate activation group was statistically significantly higher than that of the mild activation and remission group.Conclusion: We found that plasma netrin-1 levels increase with disease severity in UC, similar to proinflammatory cytokines such as TNF-alpha and IL-6.