Incidence Of Ulcerative Colitis Research Articles

Selenium-enriched Bifidobacterium Longum DD98 significantly improves the efficacy of Mesalazine and Cyclosporin A in colitis mice

The incidence of ulcerative colitis (UC) is increasing worldwide and therapeutic drugs for UC are limited. Improvement of microbiome composition with the use of probiotics has the potential to increase the therapeutic index of UC drugs. Several lines of evidence suggested that Bifidobacterium significantly improve colitis by restoring the altered gut microbiota in DSS-treated mice, however the adjuvant effect of Bifidobacterium with UC drugs remains unknown. In this study, we tested the adjuvant potential of probiotic selenium-enriched Bifidobacterium Longum DD98 (SeDD98) on Mesalazine and Cyclosporin A (CsA) two medications used in the treatment of UC. We found that SeDD98 significantly improved the efficacy of Mesalazine and CsA in UC. The combination of SeDD98 and CsA showed the strongest efficacy in decreasing colitis histological scores, inflammation, and oxidative stress. Next we demonstrated that the combination of SeDD98 and CsA shifted the gut microbiota composition and increased with higher alpha diversity as well as beneficial bacteria such as Ruminococcaceae_UCG-014 and Lachnospiraceae_NK4A136. In parallel, we assessed if the adjuvant of SeDD98 with CsA had an impact on CsA-induced kidney injury which represents one of the major side effects. We found that SeDD98 significantly improved CsA nephrotoxicity in UC mice. We then validated this observation using chronic kidney disease (CKD) mice induced by CsA administration. These results demonstrated that SeDD98 in combination with CsA was associated with increased efficacy and reduced nephrotoxicity altogether, providing the scientific basis for the adjuvant therapy of probiotics in UC.

Huaier Polysaccharide Alleviates Dextran Sulphate Sodium Salt-Induced Colitis by Inhibiting Inflammation and Oxidative Stress, Maintaining the Intestinal Barrier, and Modulating Gut Microbiota.

The incidence of ulcerative colitis (UC) is increasing annually, and UC has a serious impact on patients' lives. Polysaccharides have gained attention as potential drug candidates for treating ulcerative colitis (UC) in recent years. Huaier (Trametes robiniophila Murr) is a fungus that has been used clinically for more than 1000 years, and its bioactive polysaccharide components have been reported to possess immunomodulatory effects, antitumour potential, and renoprotective effects. In this study, we aimed to examine the protective effects and mechanisms of Huaier polysaccharide (HP) against UC. Based on the H2O2-induced oxidative stress model in HT-29 cells and the dextran sulphate sodium salt (DSS)-induced UC model, we demonstrated that Huaier polysaccharides significantly alleviated DSS-induced colitis (weight loss, elevated disease activity index (DAI) scores, and colonic shortening). In addition, HP inhibited oxidative stress and inflammation and alleviated DSS-induced intestinal barrier damage. It also significantly promoted the expression of the mucin Muc2. Furthermore, HP reduced the abundance of harmful bacteria Escherichia-Shigella and promoted the abundance of beneficial bacteria Muribaculaceae_unclassified, Anaerotruncus, and Ruminococcaceae_unclassified to regulate the intestinal flora disturbance caused by DSS. Nontargeted metabolomics revealed that HP intervention would modulate metabolism by promoting levels of 3-hydroxybutyric acid, phosphatidylcholine (PC), and phosphatidylethanolamine (PE). These results demonstrated that HP had the ability to mitigate DSS-induced UC by suppressing oxidative stress and inflammation, maintaining the intestinal barrier, and modulating the intestinal flora. These findings will expand our knowledge of how HP functions and offer a theoretical foundation for using HP as a potential prebiotic to prevent UC.

Real-World Treatment Patterns and Healthcare Resource Use for Ulcerative Colitis and Crohn's Disease in Italy.

Real-world data are used to inform decision-makers and optimise therapeutic management for patients with ulcerative colitis (UC) and Crohn's disease (CD). We analysed data on the epidemiology (by using proxies of prevalence and incidence), patient characteristics, treatment patterns and associated healthcare direct costs for the management of patients with UC and patients with CD in Italy. This retrospective observational study used administrative databases from eight Local Health Units geographically distributed across Italy. Adult patients with a hospitalisation and/or an exemption for UC or CD were included. Study outcomes were summarised descriptively, and limited statistical tests were performed. At baseline, 9255 adults with UC and 4747 adults with CD were included. Mean (standard deviation) age at inclusion was 54.0 (18.4)/48.6 (18.1) years, for UC/CD. The estimated average incidence of UC and CD for the period2013-2020 was 36.5 and 18.7 per 100,000, respectively. The most frequently prescribed drug category for patients with UC/CD was conventional treatment [mesalazine and topical corticosteroids (67.4%/61.1%), immunomodulators and systemic corticosteroids (43.2%/47.7%)], followed by biologic treatments (2.1%/5.1%). The mean annual total direct cost per patient was 7678euro (€), for UC and €6925 for CD. This analysis, carried-out in an Italian clinical setting, may help to optimise therapy for patients with UC and CD and provide relevant clinical practice data to inform decision-makers.

Comparing the efficacy of vedolizumab between males and females: a post-hoc analysis of GEMINI-1 and VARSITY.

Vedolizumab is a first-line treatment option for ulcerative colitis. There are differences in incidence of ulcerative colitis between males and females, but whether sex affects treatment outcomes is less clear. We examined sex-based differences in patients with ulcerative colitis initiated on vedolizumab from two major randomized controlled trials (RCTs). We conducted a post-hoc analysis on participants with ulcerative colitis from the VARSITY and GEMINI-1 RCTs who received vedolizumab. Outcomes of interest were rates of clinical improvement, clinical remission, and endoscopic improvement at weeks 6, 14, and 52 in male and female participants, as were differences in concentrations of trough vedolizumab and C-reactive protein; 1009 persons in GEMINI-1 and VARSITY trials were included. Male and female patients had similar disease characteristics aside from males being more likely to have Mayo 3 grade endoscopic severity at baseline (62.8 vs. 48.9%, P < 0.001). At week 6, females were more likely to have endoscopic improvement (47.4 vs. 35.2%, P = 0.001) and increased vedolizumab trough levels [34.0 (23.0-44.5) vs. 28.9 (19.0-34.6), P < 0.001]. The probability of achieving clinical remission (28.9 vs. 34.5%, P = 0.057) or endoscopic improvement (35.5 vs. 39.3%, P = 0.212) at week 52 was not different between males and females. Females with ulcerative colitis treated with vedolizumab appear more likely to achieve early endoscopic improvement than males, though longer-term outcomes demonstrated no difference. Further studies are required to better understand mechanisms through which sex or sex-associated factors could influence response to therapy in ulcerative colitis.

Mechanism of Nicotiflorin in San-Ye-Qing rhizome for anti-inflammatory effect in ulcerative colitis

BackgroundThe incidence of ulcerative colitis (UC) is on the rise globally and the development of drugs targeting UC is urgent. Finding the target of action of natural products is important for drug discovery, elucidation of drug action mechanism, and disease mechanism. San-Ye-Qing (SYQ), is an ancient herbal medicine, but whether the powder of its rhizome has pharmacological effects against UC and its mechanism of action are not clear. PurposeTo evaluate the therapeutic effectiveness of rhizome powder of SYQ in treating UC, and conduct an isolation and characterization of the chemical constituents of the powder. Further, screen the most potent compounds among them and determine the potential mechanism for treating UC. MethodsIn vivo, the therapeutic effect of SYQ's rhizome powder on UC was assessed by mice's body weight, DAI score, colon length, tissue MPO activity, serum inflammatory markers, etc. Additionally, HPLC was used to isolate and identify the specific chemical components of SYQ's rhizome powder. Then, the most effective compounds and their therapeutic targets were analysed and screened in SYQ rhizome powder using network pharmacology, combined with CCK-8 assay, NO release assay and molecular docking assay, in conjunction with CETSA, DARTS, SPR and enzyme activity assay. Finally, the biological effects of the key compound on the targets were validated using Western blot and ELISA. ResultsIn vivo, SYQ rhizome powder effectively restored mice's body weight, lowered DAI and pathological score, downregulated the expression of inflammatory biomarkers, and restored colon length, as well as the colonic epithelial and mucus barriers. Afterward, 9 compounds were isolated and identified from the powder of the rhizomes of SYQ by HPLC. Nicotiflorin is the primary compound in SYQ with the highest concentration. According to both CCK-8 and NO release tests, Nicotiflorin is also the most efficacious compound. Combined with network pharmacological prediction, molecular docking analysis, CETSA, DARTS, SPR and enzyme activity assay, Nicotiflorin may ultimately suppress inflammation by targeting p65 and inhibiting the NF-κB pathway, thereby attenuating the activation of NLRP3 inflammasome. To verify this conclusion, Western blot and ELISA experiments were conducted. ConclusionsOur results suggest that the extract from SYQ rhizomes has therapeutic properties for UC. Its active ingredient Nicotiflorin exerted potent anti-UC effects by binding to p65 and inhibiting the activation of NF-κB and NLRP3 inflammasomes.

Integration of transcriptomics and metabolomics identify biomarkers of aberrant lipid metabolism in ulcerative colitis

BackgroundThe incidence of ulcerative colitis (UC) continues to rise globally, but effective therapeutic targets are still lacking. In recent years, numerous studies have indicated that lipid therapies could offer a novel perspective for UC treatment. Given the absence of prior research utilizing high-throughput data to identify target genes associated with lipid metabolism, we conducted this work. MethodsThe training set for this study was derived from four datasets within the Gene Expression Omnibus (GEO), encompassing a total of 357 UC patients. We employed four machine learning methods (LASSO, SVM, RF, and Boruta) to jointly identify core biomarkers in these patients, whose aberrant expression needed to be validated in independent datasets and in dextrose sulfate sodium salt (DSS)-induced UC mouse models. Regarding metabolomics, we detected abnormal oxidized lipids in the serum of UC mouse using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in conjunction with orthogonal partial least squares-discriminant analysis (OPLS-DA). ResultsPhospholipase A2 Group IIA (PLA2G2A) was first identified as a possible biomarker for UC, with AUC values of 0.810 and 1.000 in the two validation sets, while in animal models the gene showed similarly significant up-regulation in damaged intestinal mucosa. Further analysis of this gene showed that it was positively correlated with 17 immune cell types and histological severity. Additionally, we pioneered the development of a lipid metabolism score in UC research, which outperformed all individual genes in terms of disease diagnostic efficacy (AUC values of 0.980 and 1.000 for the two validation sets, respectively). Finally, the metabolomics study also identified 31 significantly abnormal oxidized lipids, including 12-HHT and DHA. ConclusionsPLA2G2A is a key therapeutic target for UC, and oxidized lipids such as 12-HHT can serve as potential serologic indicators for diagnosis.

Exercise-induced β-hydroxybutyrate promotes Treg cell differentiation to ameliorate colitis in mice.

Increasing attention is being paid to the mechanistic investigation of exercise-associated chronic inflammatory disease improvement. Ulcerative colitis (UC) is one type of chronic inflammatory bowel disease with increasing incidence and prevalence worldwide. It is known that regular moderate aerobic exercise (RMAE) reduces the incidence or risk of UC, and attenuates disease progression in UC patients. However, the mechanisms of this RMAE's benefit are still under investigation. Here, we revealed that β-hydroxybutyrate (β-HB), a metabolite upon prolonged aerobic exercise, could contribute to RMAE preconditioning in retarding dextran sulfate sodium (DSS)-induced mouse colitis. When blocking β-HB production, RMAE preconditioning-induced colitis amelioration was compromised, whereas supplementation of β-HB significantly rescued impaired β-HB production-associated defects. Meanwhile, we found that RMAE preconditioning significantly caused decreased colonic Th17/Treg ratio, which is considered to be important for colitis mitigation; and the downregulated Th17/Treg ratio was associated with β-HB. We further demonstrated that β-HB can directly promote the differentiation of Treg cell rather than inhibit Th17 cell generation. Furthermore, β-HB increased forkhead box protein P3 (Foxp3) expression, the core transcriptional factor for Treg cell, by enhancing histone H3 acetylation in the promoter and conserved noncoding sequences of the Foxp3 locus. In addition, fatty acid oxidation, the key metabolic pathway required for Treg cell differentiation, was enhanced by β-HB treatment. Lastly, administration of β-HB without exercise significantly boosted colonic Treg cell and alleviated colitis in mice. Together, we unveiled a previously unappreciated role for exercise metabolite β-HB in the promotion of Treg cell generation and RMAE preconditioning-associated colitis attenuation.

MACHINE LEARNING CLASSIFICATION OF THE EPIDEMIOLOGIC STAGES OF INFLAMMATORY BOWEL DISEASE ACROSS GEOGRAPHY AND TIME

Abstract BACKGROUND Epidemiologic stages of inflammatory bowel disease (IBD) have been proposed: 1. Emergence (low incidence and prevalence); 2. Acceleration in Incidence (rapidly rising incidence, low prevalence); and 3. Compounding Prevalence (stabilizing incidence, rapidly rising prevalence). To date, these stages have been theoretical without quantified definitions of incidence and prevalence. AIM To use machine learning to determine incidence and prevalence ranges corresponding to the epidemiologic stages and provide stage classifications across time for global regions. METHODS We built a supervised random forest classifier in R to determine epidemiologic stages of IBD from population-based studies (n=340), a subset derived from a systematic review on the incidence and prevalence of IBD. A labelled training data set comprising rates of incidence and prevalence of Crohn’s disease (CD) and ulcerative colitis (UC) extracted from the systematic review was used to predict classifications of stage 1, stage 2, or stage 3 for each region, stratified by decade (1960–2019). Model accuracy was measured using a blind validation data set. The validated model was then used to predict stage classifications for regions in the data set. Interquartile ranges for incidence and prevalence of CD and UC were calculated on the random forest output, and the distributions were compared using negative binomial regression. RESULTS The random forest’s classification accuracy on the blinded validation data was 93.7% (95%CI: 90.6, 96.1) indicating an appropriate model fit and performance. Significant differences between all stages for the incidence and prevalence of CD and UC (p&amp;lt;0.001) were found. The clear distinction across stages defines the incidence and prevalence ranges (25th–75th, per 100,000) for IBD as: CD incidence 0.0–0.3, UC incidence 0.2–0.7, CD prevalence 0.3–2.2, and UC prevalence 1.7–8.1 for stage 1; CD incidence 1.0–4.4, UC incidence 2.3–6.3, CD prevalence 9.0–33.9, and UC prevalence 22.8–73.3 for stage 2; and CD incidence 6.6–14.0, UC incidence 10.1–18.1, CD prevalence 163.2–274.7, and UC prevalence 189.1–323.2 for stage 3 (Figure 1). A decade-by-decade analysis shows global regions transitioning across the epidemiologic stages (Figure 2). By the 2010s, North America, Scandinavia, Western Europe, Australia, and New Zealand were in stage 3. Most regions in Asia and Latin America were in stage 1 in the last half of the 20th century, with many transitioning to stage 2 in the 2010s. DISCUSSION Temporal incidence and prevalence data show that regions transition across epidemiologic stages. Numerical definitions of the epidemiologic stages can be used to establish the anticipated burden growth of IBD by providing estimated rates of the number of incident and prevalent IBD cases a region can expect as it transitions between IBD epidemiologic stages in the future. Figure 1 Coalescing ranges for incidence (panel A) and prevalence (panel B) by Crohn’s disease and ulcerative colitis at epidemiologic stage 1, stage 2, and stage 3. Data were categorized by data type (incidence or prevalence), disease type (Crohn’s disease or ulcerative colitis), and epidemiologic stage, as per results from the random forest classifier. The 25th and 75th percentiles were calculated using the rates across all regions included in the analysis for all available time points for each box group. Figure 2 Global maps depicting epidemiologic stages of IBD evolution from 1960 to 2019 broken down by decade, as predicted by the random forest model. Panel A contains stage classifications from 1960 to 1969; panel B contains stage classifications from 1970 to 1979; panel C contains stage classifications from 1980 to 1989; panel D contains stage classifications from 1990 to 1999; panel E contains stage classifications from 2000 to 2009; and panel F contains stage classifications from 2010 to 2019.

UNRAVELING THE CONNECTION: RACIAL INFLUENCE ON THE DEVELOPMENT OF ULCERATIVE COLITIS AFTER BARIATRIC SURGERY

Abstract INTRODUCTION Bariatric surgery is an effective treatment for obesity and aids in enhancing metabolic health. However, it has been observed that there's a heightened occurrence of Ulcerative Colitis (UC), especially following Roux-en-Y gastric bypass surgery. This study aims to ascertain whether racial differences influence the risk of developing Ulcerative Colitis in patients who have undergone bariatric surgery. Illuminating this relationship is key to improving patient outcomes and refining care following surgery. METHODS Our retrospective analysis reviewed patients who underwent bariatric surgery at our facility between 2009 and 2022. We collected data concerning comorbidities, insurance statuses, types of surgical procedures, colonoscopy, pathology reports, and baseline characteristics, employing ICD and CPT codes. We monitored patients who manifested Ulcerative colitis (UC) after surgery until 2023, categorizing them by gender, race, and the time elapsed. To balance baseline characteristics, we used propensity score matching. Patients with a history of UC before surgery were omitted from the study. We utilized Kaplan-Meier survival analysis and Cox proportional hazards models to determine the timing of UC onset across different racial groups. We applied odds ratios to discern independent factors impacting the study's outcomes. RESULTS Between 2009 and 2022, our facility performed 960 bariatric surgeries. Of these procedures, 24 patients (or 0.02%) were diagnosed with UC, typically identified around 80±14.2 months post-surgery. The mean age of the participants was approximately 46±11.8 years, and females constituted 54.2% of the cohort. When examining racial breakdowns, 38.39% were African Americans, 24.4% were whites, 21% were Asians, and 16.21% were Hispanics. Notably, Hispanic patients manifested UC within a considerably shorter duration than other racial groups (Breslow: 11.836, p=0.022). Additionally, a heightened risk of UC was observed among individuals from the lowest income bracket (OR: 3.15, P=0.041), emphasizing the influence of socioeconomic status on health outcomes. DISCUSSION This research contributes to bridging the knowledge deficit regarding the influence of race on the occurrence of UC following bariatric surgery. Our retrospective examination of 960 surgeries from 2009 to 2022 indicated a 0.02% incidence of UC, usually identified approximately 45 months after surgery. Importantly, Hispanic patients experienced the onset of UC in a notably shorter period compared to other racial groups, with those in lower income brackets encountering elevated risk levels. Continued studies in this domain can facilitate the development of interventions to diminish these risks, thereby improving health outcomes for a broad spectrum of patient demographics.

TRENDS IN INFLAMMATORY BOWEL DISEASE INCIDENCE AND PREVALENCE ACROSS EPIDEMIOLOGIC STAGES: A GLOBAL SYSTEMATIC REVIEW WITH META-ANALYSIS

Abstract BACKGROUND Rising incidence and prevalence of inflammatory bowel disease (IBD) observed historically in early-industrialized regions now also appear in newly-industrialized and emerging regions. The epidemiology of IBD has been proposed to progress across epidemiologic stages: 1. Emergence (low incidence and prevalence); 2. Acceleration in Incidence (rapid rising incidence); and 3. Compounding Prevalence (stabilizing incidence, rapid rising prevalence). AIM To gather real-world data on the incidence and prevalence of IBD and characterize global regions in each epidemiologic stage by meta-analyses. METHODS Two previous systematic reviews (database inception–2010; 2010–2016) were updated with a search of MEDLINE, Embase, PubMed, and Web of Science (2017–2023) to identify all population-based studies reporting the incidence or prevalence of Crohn’s disease (CD) or ulcerative colitis (UC). International partners provided a secondary review of the included studies from their local regions. Incidence and prevalence rates (per 100,000 population), stratified by epidemiologic stage, were meta-analyzed to determine pooled rates with associated 95% confidence intervals (95%CI). A Cochrane Q test was used to investigate differences between epidemiologic stages for both CD and UC. RESULTS After assessing 1,250 manuscripts, a total of 491 studies (439 incidence, 228 prevalence) from 80 global regions spanning 1920-2022 were identified by the systematic review (Figure 1). All data identified with our search strategy are available to view in an open-access, online interactive data repository (https://gives21.shinyapps.io/dashboard/) created with Shiny for R. The pooled incidence of CD and UC per 100,000 person-years rose from 0.28 (95%CI: 0.21, 0.36) and 0.57 (95%CI: 0.47, 0.69) in Stage 1 to 2.13 (95%CI: 1.88, 2.42) and 4.05 (95%CI: 3.65, 4.50) in Stage 2 to 9.34 (95%CI: 8.73, 9.99) and 14.07 (95%CI: 13.09, 15.12) in Stage 3 (Table 1). Similarly, the pooled prevalence of CD and UC per 100,000 persons rose from 1.96 (95%CI: 1.41, 2.74) and 6.35 (95%CI: 4.45, 9.07) in Stage 1 to 22.18 (95%CI: 17.96, 27.38) and 45.36 (95%CI: 37.84, 54.38) in Stage 2 to 186.18 (95%CI: 163.18, 212.42) and 255.92 (95%CI: 230.60, 284.02) in Stage 3 (Table 1). Subgroup analysis confirmed differences in both incidence and prevalence for CD and UC between epidemiologic stages (p&amp;lt;0.001). DISCUSSION This is the most comprehensive systematic review on the incidence and prevalence of IBD. The amalgamated real-world data from this study highlight the rising global burden of IBD across three distinct epidemiologic stages: 1. Emergence, 2. Acceleration in Incidence, and 3. Compounding Prevalence. Figure 1 Systematic review study selection flowchart including a brief overview of two previous systematic reviews: Molodecky, N.A. et al. Gastroenterology. 2012;142(1):46-54 and Ng, S.C. et al. Lancet. 2017;390(10114):2769-78. Table 1 Pooled incidence and prevalence rates per 100,000 population for Crohn’s disease and ulcerative colitis. Cochrane Q subgroup analysis for difference in estimates between epidemiologic stages. † Represents the number of study-subregion groups used in the calculation of pooled rates and their 95% confidence intervals.

P1172 Epidemiology and initial presentation of newly diagnosed inflammatory bowel diseases in a Danish population-based inception cohort – results from the IBD Prognosis Study

Abstract Background It is unclear whether the incidence of inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), continues to increase. In this study, we aimed to investigate the occurrence and initial disease presentation of IBD in a population-based setting. In addition, we aimed to identify predictors of an early severe disease presentation. Methods The study was conducted as part of IBD Prognosis Study, an ongoing Danish prospective population-based inception cohort study that includes incident patients with IBD according to the Copenhagen Diagnostic Criteria since May 2021, covering the catchment areas of approximately 20% of the Danish population (1.1 million). In this analysis, cutoff for data analysis was in May 2023. Crude incidence rates and European Standard Population (ESP)-adjusted rates were calculated. A multivariable logistical regression model was constructed to identify predictors of a severe disease presentation, defined as the composite need for systemic steroids, immunomodulators, biologics, or IBD-related surgery within three months of disease. Results In total, 554 patients (UC: 344, CD: 210) fulfilled the inclusion criteria, resulting in the following crude incidence rates per 100,000 person-years: IBD 23.4 (95% CI 21.5-25.4), UC 14.0 (12.6-15.6), and CD 8.6 (7.4-9.8). ESP-adjusted rates were: IBD 20.4 (18.2-22.9), UC 11.8 (10.2-13.0), and CD 7.9 (6.5-9.9) (Figure 1). Among patients with UC, 81 (26.3%) and 95 (30.8%) had left-sided or extensive colitis at disease onset, respectively, while 61 (30.3%) and 62 (30.8%) patients with CD had ileal or ileocolonic disease. Stricturing or penetrating CD behaviour was observed in 24 (11.9%) and 11 (5.5%) patients, respectively. A high proportion of patients needed hospitalization (CD: 68 (33.8%), UC: 60 (19.5%), p=0.001) and IBD-related surgery (CD: 21 (10.4%), UC: 10 (3.2%), p=0.004) at the time of diagnosis. In multivariable analysis, a severe disease presentation of UC at the time of diagnosis was associated with left-sided or extensive disease distribution, thrombocytosis, and increased levels of C-reactive protein (CRP) (Table 1). In patients with CD, stricturing, or perianal disease, as well as anemia, levels of albumin, CRP, and calprotectin were predictive of this endpoint (Table 1). Conclusion The incidence of UC and CD in Denmark appears stable compared to historical data from the previous decades.1 The study identified clinical predictors of a severe disease presentation from the time of diagnosis, emphasizing the critical need for early risk stratification and intervention strategies. Reference: 1 Dorn-Rasmussen M et al., J Crohns Colitis. doi: 10.1093/ecco-jcc/jjac138.

P880 The real-world use of five-aminosalicylate (5ASA) treatment for Ulcerative Colitis in Australia and New Zealand: Crohn’s Colitis Cure (CCC) data insight’s program

Abstract Background Five-aminosalicylates (5ASAs) promote &amp; maintain remission in people with ulcerative colitis (UC) and are administered orally or rectally, with combination therapy (oral + rectal) more effective than oral monotherapy, especially when treating flares1. 5ASAs may be perceived as out-dated and thus neglected. With increasing UC incidence &amp; prevalence in emerging nations, understanding real-world 5ASA use and value is vital. Methods Crohn’s Colitis Care is a cloud-based electronic medical record used in Australasia. Data feed into a de-identified clinical quality registry (CQR), which was interrogated in September 2023. People with UC under active care (encounter within 14 months) were included. Results Of the 2,522 eligible people, 78.4% resided in Australia &amp; 21.6% in New Zealand (NZ). The median age was 41 years (IQR 31-56), with an even gender distribution (50.3% female). Median disease duration was 9 years (IQR 4.4-16.7). Median duration of follow up was 25.9 months (IQR 13.0-41.4). Overall, 39.2% (n=989) had no documentation of 5ASA therapy (42.0% in Australia, 28.9% in NZ; Table 1). In those with documented 5ASA therapy (60.8%, n=1,534), the average 5ASA treatment duration was 9 years (IQR 4.4-16.7) and women were more likely to receive rectal administration than men (p&amp;lt;0.05). In those who ceased 5-ASA therapy, 782 (44.8%) had a reason documented, with the most common being medication rationalisation and/or deep remission (40.0%) (Figure 1), usually due to up-titration to a more advanced therapy. A total of 608 (39.6%) were recorded as already receiving additional IBD therapy at CQR entry (immunomodulators [IMs]/biologics/small molecules). Of those receiving 5ASAs alone at CQR entry (n=926), 5ASAs were subsequently judged to have failed in 37.8% (n=350). 5ASA failure was defined as the need for additional IBD therapies (99.1%, n=230 for IMs/biologics/small molecules and n=117 for steroids, total n=347); hospitalisation (n=3, 0.9%) or IBD surgery (n=0). Conclusion Despite not working for everyone, the long duration of 5ASA therapy indicates they are well tolerated &amp; perceived as beneficial by consumers. There was greater 5ASA utilisation in NZ, possibly due to restricted advanced therapy access. Gender-specific trends in 5ASA administration were identified, raising the question as to why this should be so, given this is not obviously explained by disease phenotype. Further analysis is needed to tease out how such trends interact with other therapeutic access, choices and outcomes. 1 - Probert C et a. Combined oral and rectal mesalazine for the treatment of mild-to-moderately active ulcerative colitis: rapid symptom resolution and improvements in quality of life. J Crohns Colitis. doi:10.1016/j.crohns.2013.08.007

A systematic review and meta-regression on international trends in the incidence of ulcerative colitis in children and adolescents associated with socioeconomic and geographic factors

The incidence of ulcerative colitis (UC) among children and adolescents is rising globally, albeit with notable discrepancies across countries. This systematic review and meta-analysis aims to provide a comprehensive overview of the incidence rates of pediatric UC in various countries and explore potential influencing factors. A systematic literature search was conducted in PubMed and EMBASE (via OVID) for studies published between January 1, 1970, and December 31, 2019. Additionally, a manual search was performed to identify relevant systematic reviews. Meta-analyses and meta-regressions were employed to determine the overall incidence rate and examine potential factors that may influence it. A total of 66 studies were included in the qualitative analysis, while 65 studies were included in the meta-analysis and 50 studies were meta-regression. The study reports a rising incidence of pediatric UC in several countries but significant differences across geographic regions, with no discernible global temporal trend. In addition, our meta-regression analysis showed that geographic location and socioeconomic factors significantly influenced the incidence of UC.Conclusion: Our findings indicate a rising incidence of pediatric UC in numerous countries since 1970, but with significant geographical variation, potentially presenting challenges for respective healthcare systems. We have identified geographic and socioeconomic factors that contribute to the observed heterogeneity in incidence rates. These findings provide a foundation for future research and health policies, aiming to tackle the growing burden of UC among children and adolescents.What is Known:• The incidence of ulcerative colitis in childhood and adolescence appears to be increasing worldwide and varies internationally.• Environmental and lifestyle factors are suspected as potential causes.What is New:• Our results highlight that the heterogeneity in incidence rates can be attributed to geographic and socio-economic factors.

The concept of the development of inflammatory bowel diseases as a consequence of intestinal metabolic dysbiosis

The article discusses the high relevance of the problem of inflammatory bowel diseases (IBD). First of all, attention is drawn to the annual increase in the incidence of ulcerative colitis and Crohn’s disease. Factors that can influence the development of IBD are assessed. A diagram of the pathogenetic cascade of dysbiotic disorders is presented, manifested by an increase in the blood serum of metabolic products of the intestinal microflora, microvascular, metabolic and immune changes leading to the triggering of inflammation in the intestinal wall.

The UDP-glucose/P2Y14 receptor axis promotes eosinophil-dependent large intestinal inflammation.

Ulcerative colitis (UC) is a chronic disorder of the large intestine with inflammation and ulceration. The incidence and prevalence of UC have been rapidly increasing worldwide, but its etiology remains unknown. In patients with UC, the accumulation of eosinophils in the large intestinal mucosa is associated with increased disease activity. However, the molecular mechanism underlying the promotion of intestinal eosinophilia in patients with UC remains poorly understood. Here, we show that uridine diphosphate (UDP)-glucose mediates the eosinophil-dependent promotion of colonic inflammation via the purinergic receptor P2Y14. The expression of P2RY14 mRNA was upregulated in the large intestinal mucosa of patients with UC. The P2Y14 receptor ligand UDP-glucose was increased in the large intestinal tissue of mice administered dextran sodium sulfate (DSS). In addition, P2ry14 deficiency and P2Y14 receptor blockade mitigated DSS-induced colitis. Among the large intestinal immune cells and epithelial cells, eosinophils highly expressed P2ry14 mRNA. P2ry14-/- mice transplanted with wild-type bone marrow eosinophils developed more severe DSS-induced colitis compared with P2ry14-/- mice that received P2ry14-deficient eosinophils. UDP-glucose prolonged the lifespan of eosinophils and promoted gene transcription in the cells through P2Y14 receptor-mediated activation of ERK1/2 signaling. Thus, the UDP-glucose/P2Y14 receptor axis aggravates large intestinal inflammation by accelerating the accumulation and activation of eosinophils.

Role of Age as a Predictor of Major Complications After Elective Surgery for Ulcerative Colitis.

The incidence of ulcerative colitis (UC) in the elderly population is increasing. The aim of this study was to assess the degree to which age and other factors increase the risk of developing major complications in patients undergoing elective surgery for UC. Using the ACS-NSQIP database from 2016 to 2020, patients undergoing elective surgery for UC were divided into four categories: younger than 30, 30-49, 50-69, and 70 or older. A composite outcome was created including major complications and multivariable analysis was performed to identify factors associated with composite major complications. 5946 patients diagnosed with ulcerative colitis who underwent elective surgery were included in the analysis. 14.1% of all patients developed a major complication. For patients with UC, factors associated with the development of a major complication were age 50-69 (OR 1.31, P = .034), male sex (OR 1.38, P < .001), Black race (OR 1.47, P = .049), dependent status (OR 2.06, P = .028), hypoalbuminemia (OR 1.92, P < .001), preoperative steroid treatment (OR 1.27, P = .038), preoperative transfusion (OR 1.91, P < .001), open surgical approach (OR 1.44, P = .002), and partial colectomy (OR 1.51, P = .007). Specifically in patients aged 70 or older, hypoalbuminemia (OR 3.20, P < .001) and preoperative transfusion (OR 2.78, P = .019) were associated with a major complication. Age is a risk factor for the development of a major complication in UC patients undergoing elective surgery. However, it is not the only risk factor nor is it the one that increases the risk the most.

Sea Cucumber Peptides Ameliorate DSS-Induced Ulcerative Colitis: The Role of the Gut Microbiota, the Intestinal Barrier, and Macrophage Polarization.

The incidence of ulcerative colitis (UC) is increasing annually. There are few treatments for UC patients, and some drugs have serious side effects. Sea cucumber peptide (SCP) has anti-inflammatory, antioxidant and other biological activities, and various sea cucumber species are in pharmaceutical development. However, relevant studies on the effects of SCP on UC progression are still lacking. In this study, a mouse model of acute colitis was induced by 3% dextran sulfate (DSS), and the effect of 500 mg/kg SCP on colitis was investigated. The results showed that SCP can alleviate DSS-induced colon damage and intestinal barrier damage. SCP significantly inhibited the expression of inflammatory factors and oxidative stress in UC mice. SCP reversed the intestinal microbiota dysregulation induced by DSS, inhibited the growth of Sutterella, Prevotella_9 and Escherichia-Shigella harmful bacteria, and increased the abundance of Lachnospiraceae_NK4A136_group. At the same time, SCP treatment significantly inhibited the LPS-induced polarization of M1 macrophages, which may be mediated by two monopeptides, IPGAPGVP and TGPIGPPGSP, via FPR2. In conclusion, SCP can protect against colitis by modulating the intestinal microbiota composition and the intestinal barrier and inhibiting the polarization of M1 macrophages.

Revisiting the relationship between complement and ulcerative colitis.

Ulcerative colitis (UC) is an inflammatory bowel disorder (IBD) characterized by relapsing chronic inflammation of the colon that causes continuous mucosal inflammation. The global incidence of UC is steadily increasing. Immune mechanisms are involved in the pathogenesis of UC, of which complement is shown to play a critical role by inducing local chronic inflammatory responses that promote tissue damage. However, the function of various complement components in the development of UC is complex and even paradoxical. Some components (e.g. C1q, CD46, CD55, CD59, and C6) are shown to safeguard the intestinal barrier and reduce intestinal inflammation, while others (e.g. C3, C5, C5a) can exacerbate intestinal damage and accelerate the development of UC. The complement system was originally thought to function primarily in an extracellular mode; however, recent evidence indicates that it can also act intracellularly as the complosome. The current study provides an overview of current studies on complement and its role in the development of UC. While there are few studies that describe how intracellular complement contributes to UC, we discuss potential future directions based on related publications. We also highlight novel methods that target complement for IBD treatment.

Incidence of Inflammatory Bowel Disease in Urban China: A Nationwide Population-based Study

Limited studies have evaluated the burden of inflammatory bowel disease (IBD) in China. We aimed to estimate the incidence of IBD including ulcerative colitis (UC) and Crohn's disease (CD) in urban China. The national urban incidence in 2016 was calculated based on urban basic medical insurance from 2012 to 2016 in China by using a 4-year washout period. The incidence in Yinzhou District estimated from the Yinzhou electronic health care record database was used to test the accuracy of the results from insurance data. A total of 95,555 patients with IBD were identified. The incidence in 2016 was 10.04 (95% confidence interval, 6.95-13.71) per 100,000 person-years. The incidence rates of both UC and CD were higher among males than among females. There was a sharp increase in UC incidence before the age of 30 years and stabilization in later years (50-79 years old), whereas CD incidence peaked at 30 to 34 years old and experienced decline subsequently. The incidence of UC was much greater than that of CD, with a UC-to-CD incidence ratio of 12.61. The results from the Yinzhou database confirmed these results. This study is the first to draw a portrait of the distribution of IBD in urban China. The difference in IBD incidence between urban China and other countries suggests an association between the IBD burden and industrialization process. The accelerating urbanization and industrialization process in China, a country with a population of 1.4 billion people, will likely increase the burden of IBD.

The methodology of the development of original medicines based on the medicinal plant raw material for the treatment of inflammatory bowel diseases

According to the Ministry of Health of Ukraine, the number of patients with IBD in Ukraine is approximately 30,000 people per 100,000 population, half of which have a medium or severe degree of damage.&#x0D; Over the past 5 years, there has been a trend towards an increase in the number of severe cases and treatment-resistant forms of chronic intestinal diseases of an inflammatory nature, which often requires surgical intervention or causes the development of complications, which, in turn, can lead to invalidation of patients and, as a result, causes significant economic costs, related to their care, treatment and rehabilitation. The most common are Crohn’s disease and ulcerative colitis.&#x0D; The prevalence of ulcerative colitis (UC) in the population ranges from 21 to 268 cases per 100,000 people. The social significance of UC lies in the fact that the incidence is predominant among young people. Thus, statistical data show that the peak incidence of UC occurs at the age of 20–30 years. In the absence of appropriate therapy, the course of UC is recurrent and remitting.&#x0D; In the process of work, the methods of analysis of electronic and paper sources of information were used, on providing the domestic pharmaceutical market with drugs for the treatment of IBD, their directions and mechanism of action, the possibility of using in the therapy of diseases with herbal medicines containing BAS, that affect various links of the pathogenetic process, the possibility of combining it with synthetic API in order to increase the effectiveness of treatment.&#x0D; The algorithm of the methodology consists of three blocks: information and search, research and biological. Each block, which ends with obtaining an intermediate result, ensures the setting of the task for the next stage of the research.