Onset Of Ulcerative Colitis Research Articles

Like a Punch in the Gut: A Novel Perspective On Annual Recurrences of Ulcerative Colitis.

Ulcerative colitis (UC), a chronic inflammatory bowel disease, causes stomach pain, diarrhea, and rectal bleeding. The exact cause is unknown, but it is thought to involve genetic, environmental, and psychological factors. Some people experience annual flare-ups without obvious reason. This article adopts a theory-driven approach to consider how and why past traumatic events may contribute to annual flare-ups. We applied learning theory, which explains the development of re-experiencing phenomena in post-traumatic stress disorder (PTSD), to better understand the occurrence of annual flares in patients living with UC. Two possibilities emerged in which associative learning may contribute to annual UC flares. First, flare-ups could be a physical response to sensory cues in the present that overlap with trauma experienced at the first onset of UC. Annual episodes may strengthen the UC flare as a learned physiological response to trauma reminders. Second, flare-ups may result from elevated stress due to trauma re-experiencing at anniversaries. Sensory features of the initial UC trauma may be associated with strong reactions, which generalize to similar stimuli, triggering re-experiencing symptoms and increasing psychological stress. Elevated stress raises glucocorticoid levels, promoting UC-specific inflammation. Stimulus discrimination from cognitive therapy for PTSD may help to over-ride the associations that have formed between sensory features of past trauma, linked reactions, and similar cues in the present. Research is needed to understand how traumatic events influence the onset and recurrence of ulcerative colitis, as well as the potential benefits of stimulus discrimination for reducing the frequency of annual flares.

Fecal bile acid profiles before and after fecal microbial transplant in pediatric onset ulcerative colitis

Fecal bile acid profiles before and after fecal microbial transplant in pediatric onset ulcerative colitis

Anorexia and bulimia in relation to ulcerative colitis: a Mendelian randomization study.

Evidence for anorexia and bulimia in relation to the risk of ulcerative colitis (UC) is limited and inconsistent. The objective of this research was to utilize bi-directional, two-sample Mendelian randomization (MR) analysis to predict the causal association between anorexia nervosa and bulimia nervosa with UC. The genome-wide association studies (GWAS) provided data for anorexia and bulimia from the UK Biobank, utilizing single-nucleotide polymorphisms (SNP) as instrumental variables. Additionally, genetic associations with UC were collected from various sources including the FinnGen Biobank, the UK Biobank and the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). The main analytical approach utilized in this study was the inverse-variance-weighted (IVW) method. To evaluate horizontal pleiotropy, the researchers conducted MR-Egger regression and MR-PRESSO global test analyses. Additionally, heterogeneity was assessed using the Cochran's Q test. This study found a negative association between genetically predicted bulimia (OR = 0.943, 95% CI: 0.893-0.996; p = 0.034) and the risk of UC in the IIBDGC dataset, indicating that individuals with bulimia have approximately a 5.7% lower risk of developing UC. No association was observed in the other two datasets. Conversely, genetically predicted anorexia was not found to be causally associated with UC. In bi-directional Mendelian randomization, UC from the IIBDGC dataset was negatively associated with the risk of anorexia (OR = 0.877, 95% CI: 0.797-0.965; p = 0.007), suggesting that UC patients have approximately a 12.3% lower risk of developing anorexia, but not causally associated with bulimia. Genetically predicted bulimia may have a negative association with the onset of UC, while genetically predicted anorexia does not show a causal relationship with the development of UC. Conversely, genetically predicted UC may have a negative association with the development of anorexia.

Therapeutic Potential of Essential Oils Against Ulcerative Colitis: A Review.

Ulcerative colitis (UC) is a chronic non-sp ecific inflammatory disease of the colorectal mucosa. Researchers have associated UC onset with familial genetics, lifestyle behavior, inflammatory immune factors, intestinal microbiota, and the integrity of the intestinal mucosal barrier. The primary therapeutic interventions for UC consist of pharmacological management to control inflammation and promote mucosal healing and surgical interventions. The available drugs effectively control and decelerate the progression of UC in most patients; nonetheless, their long-term administration can exert adverse effects and influence the therapeutic effect. Plant essential oils (EOs) refer to a group of hydrophobic aromatic volatile substances. EOs have garnered considerable attention in both domestic and international research because of their anti-inflammatory, antibacterial, and antioxidant properties. They include peppermint, peppercorns, rosemary, and lavender, among others. Researchers have investigated the role of EOs in medicine and have elucidated their potential to mitigate the detrimental effects of UC through their anti-inflammatory, antioxidant, antidepressant, and anti-insomnia properties as well as their ability to regulate the intestinal flora. Furthermore, EOs exert minimal toxic adverse effects, further enhancing their appeal for therapeutic applications. However, these speculations are based on theoretical experiments, thereby warranting more clinical studies to confirm their effectiveness and safety. In this article, we aim to provide an overview of the advancements in utilizing natural medicine EOs for UC prevention and treatment. We will explore the potential pathogenesis of UC and examine the role of EOs therapy in basic research, quality stability, and management specification of inadequate EOs for UC treatment. We intend to offer novel insights into the use of EOs in UC prevention and management.

Eosinophils and risk of ulcerative colitis in European population: Evidence from Mendelian randomization study.

Observational studies have indicated that peripheral blood eosinophil count is elevated in individuals diagnosed with ulcerative colitis (UC) and correlates with the disease activity of UC. However, this conclusion contradicts with findings from other studies. Therefore, we employed Mendelian randomization (MR) method to assess the genetic link between eosinophil count and UC. This MR study utilized summary data from genome-wide association studies (GWAS) on eosinophil count and UC. The main approach used for conducting MR analysis was the inverse variance weighted (IVW) method. Meta-analysis of the IVW results was performed alongside multiple sensitivity analyses to confirm the robustness of the MR analysis results. The IVW method unveiled a causal relationship between eosinophil count and UC (OR = 1.18, 95% CI: 1.04-1.33, p = .01) in the discovery cohort. This finding was further corroborated by the replication cohorts (OR = 1.16, 95% CI: 1.04-1.29, p = .01; OR = 1.12, 95% CI: 1.01-1.24, p = .03). The meta-analysis indicated that the overall odds ratio (OR) for all studies was 1.15 (common effect model, 95% CI: 1.08-1.23, p < .01). Sensitivity analysis suggested the absence of heterogeneity and horizontal pleiotropy in all MR analyses. Based on bidirectional two-sample MR analysis, there is an indication that elevated eosinophil count may increase the risk of UC. However, potential confounding factors cannot be ruled out, and further research is necessary to explore how eosinophils contribute to the onset and progression of UC.

Prognostic Factors in Prostate Cancer Associated with Ulcerative Colitis.

Ulcerative colitis (UC) has been associated with increased prostate cancer (PCa) risk. However, the mechanisms underlying UC and increased PCa risk remain unclear, and research on this topic is scarce in Japan. We have investigated whether UC is associated with PCa risk in the Japanese population and the risk factors related to PCa among older UC patients. This retrospective single-center cohort study was conducted between January 2010 and April 2022. A total of 68 cases were analyzed, and 9 cases of PCa were observed (13.2%). PCa occurred more frequently in the adult-onset group (8/40, 20.0%) than in the older-onset group with UC (1/28; 3.57%). No significant differences were observed between immunosuppressive therapies and PCa in patients, excluding those with pancolitis-type UC. PCa occurred more frequently in the pancolitis type, and the biologics group had no PCa cases, but the difference was not statistically significant (p = 0.07). This study suggests that pancolitis type and UC onset in middle-aged patients may be risk factors and found that biologics potentially suppress PCa development.

Brain imaging derived phenotypes: a biomarker for the onset of inflammatory bowel disease and a potential mediator of mental complications.

Inflammatory bowel disease (IBD), mainly categorized into Crohn's disease (CD) and ulcerative colitis (UC), is a chronic relapsing gastrointestinal disorder that significantly impairs patients' quality of life. IBD patients often experience comorbidities such as anxiety and depression, and the underlying mechanisms and treatment strategies remain areas of investigation. We conducted a Mendelian randomization(MR) analysis utilizing brain image derived phenotypes (IDP) from the UK Biobank database to investigate the causal relationships between IBD and alterations in brain structural morphology and connectivity of neural tracts. This study aimed to identify biological evidence linking IBD to psychiatric disorders such as anxiety and depression. Specifically, the volume of grey matter in the Left Frontal Orbital Cortex exhibited a negative association with the onset of Crohn's disease (odds ratio (OR) [95% confidence interval (CI)]: 0.315[0.180~0.551], adjusted P=0.001), while the volume of the superior frontal cortex in the right hemisphere showed a positive correlation with the development of Ulcerative colitis (OR [95% CI]: 2.285[1.793~2.911], adjusted P<0.001), and the volume of lateral occipital cortex in the left hemisphere demonstrated a positive relationship with Crohn's disease onset (OR [95% CI]: 1.709[1.671~1.747], adjusted P<0.001). In the context of reverse causality, the onset of UC or CD has led to alterations in imaging derived phenotypes associated with five disorders (anxiety, depression, schizophrenia, bipolar disorder, pain) and three functions (memory, emotion, language). Our study has demonstrated a causal relationship between IBD and IDPs. IDPs may serve as potential biomarkers for the progression of IBD and as predictive intermediaries for the development of neurological diseases in IBD patients.

Efficacy of vedolizumab during intravenous induction therapy in ulcerative colitis and Crohn's disease: post hoc analysis of patient-reported outcomes from the VISIBLE 1 and 2 studies.

Vedolizumab is an anti-α4β7 integrin antibody used to treat moderate to severe ulcerative colitis (UC) and Crohn's disease (CD). This post hoc analysis of patient-reported outcomes (PROs) from the VISIBLE 1 (NCT02611830) and 2 (NCT02611817) phase 3 studies evaluated onset of treatment effect on patient-reported symptoms during 6-week vedolizumab induction. Patient-reported stool frequency (SF) and rectal bleeding (RB) (UC Mayo score), and SF and abdominal pain (AP) in CD were collected via electronic diary from VISIBLE patients receiving one or more open-label intravenous (IV) vedolizumab induction doses (weeks 0 and 2). PRO data were analyzed using descriptive statistics. Data from 994 patients (UC 383, CD 611) showed mean ratings for all PROs declined consistently week-on-week from baseline through week 6, with early onset of improvement. By week 2, 22% of patients with UC reported RB improvement (≥1-point reduction in RB subscore, 7-day mean), rising to 45% by week 6. By week 6, 18% of patients with UC achieved SF improvement (SF subscore 0; 21% antitumor necrosis factor alpha [anti-TNFα] naive, 13% anti-TNFα experienced). SF improvement in patients with CD (reduction of ≥3 stools, 7-day mean) was achieved by 32% at week 6 (34% anti-TNFα naive, 30% anti-TNFα experienced). Fewer patients with CD reported severe/moderate AP at week 6 (5.1%/28.5%) than baseline (14.6%/61.5%). SF decline appeared greater and faster for anti-TNFα-naive vs. anti-TNFα-experienced patients (UC and CD). Results indicate early onset of patient-reported UC and CD symptom improvement during vedolizumab IV induction in VISIBLE 1 and 2.

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.

P381 Intestinal ultrasound in newly diagnosed Ulcerative Colitis predicts the need for colectomy

Abstract Background Upon diagnosis of ulcerative colitis (UC), it remains challenging to predict who will have a severe disease course, ultimately necessitating colectomy. Predictive tools capable of risk-stratifying patients and individualize treatment are warranted. The aim of this study was to assess whether Intestinal ultrasound (IUS), performed at the onset of UC, could help predict the need for colectomy within the first year of diagnosis. Methods In a Danish prospective inception cohort, all new-onset adult patients with UC (including unclassified IBD) with left-sided or extensive colitis underwent IUS near the diagnostic endoscopy. The assessment included the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) and the bowel wall thickness (BWT) of the most inflamed segment. Besides IUS, we recorded age, gender, smoking, BMI, the Mayo endoscopic score (MES), the Simple Clinical Colitis Activity Index (SCCAI), and biomarkers hemoglobin (hgb), C-reactive protein (CRP), albumin and fecal calprotectin. Results During inclusion (May 2021 – April 2023), we included 193 UC patients with Montreal classification E2 or E3. In total, 12/193 (6%) underwent colectomy within the first year or during follow-up (min. 6 months). Baseline characteristics are presented in Table 1. Univariable analyses identified high MES, CRP, SCCAI, IBUS-SAS, and BWT, along with low Hgb and albumin, as significantly associated with an increased colectomy risk. Multivariable analysis with stepwise reduction identified only SCCAI (OR: 2.0, CI 1.2–3.3, p&amp;lt;0.005) and BWT (OR: 1.6, CI 1.1–2.3, p=0.01) as independent predictors. Through ROC analysis, BWT presented the highest accuracy (AUC: 0.89), and the optimal cut-off by Youden Index for colectomy prediction was &amp;gt; 6.1 mm. Combining all the significant non-IUS predictors, CRP, MES, SCCAI, hgb, and albumin yielded an AUC of 0.88. The highest accuracy was found by combining SCCAI and BWT, with an AUC of 0.94. Kaplan-Meier curve for colectomy-free survival is presented in Figure 1. Among patients with BWT&amp;gt;6.1mm, 18/21 (86%) started systemic steroids within the first week, compared to 43/125 (34%) of patients with BWT ≤ 6.1, p=0.007. Among patients with BWT &amp;gt; 6.1mm, 11/21 (52%) started biologics within the first 31 days, compared to 5/125 (4%) of patients with BWT≤6.1mm, p&amp;lt;0.001. Despite more aggressive treatment, 8/21 (38%) with BWT&amp;gt;6.1mm had a colectomy compared to 2/125 (2%) with BWT≤6.1mm.Conclusion IUS at UC onset, specifically BWT, is a robust predictor of colectomy risk within the first year of diagnosis. Combining clinical symptom scores with IUS enhances predictive accuracy. It can accurately identify patients at an increased risk of colectomy, guiding early treatment decisions for improved patient outcomes.

N46 Stress after an Ulcerative Colitis diagnosis: examining the role of psychological factors in Ulcerative Colitis using Interpretative Phenomenological Analysis

Abstract Background People with ulcerative colitis (UC) report higher levels of stress, anxiety, and depression than the general population. 89% of people with IBD in the UK surveyed in 2019 said they found coping hard. However, most relevant research relies on generic stress questionnaires which ignore confounders typical in UC, such as fatigue. This study aims to provide rich, detailed accounts of how individuals encounter stress after a UC diagnosis. Methods An hour-long, semi-structured interview was conducted in January 2022 with a 76-year-old man, reporting high levels of perceived stress and diagnosed with UC three months previously. He was asked about stressors, coping and support during UC diagnosis and beyond. Interpretative Phenomenological Analysis (IPA) examines the detailed, unique interpretation of a significant experience to an individual. IPA methodology follows four stages: exploratory notes; formulating Experiential Statements (ESs) summarising the meaning of the experience to the interviewee; connecting similar ESs and developing Personal Experiential Themes (PETs), the three to five most important elements of the participant’s experience. Results Four PETs were formulated: My UC needs a positive, practical mental approach, not an emotional one Mixed experience with healthcare services affected my anxiety and disease management My UC symptoms and overall health affected my emotional well-being and coping I believe there is an absence of evidence on UC’s causes, cure, or helpful lifestyle changes The interviewee didn’t "dwell on these things" although he felt "it’s another thing and I’m going to have to deal with this long term". He "could email the nurse there if I had any problems and I did at one stage and got an instant reply" but at other times he felt "abandoned here because nobody is taking me seriously. I keep phoning these people up, they keep passing me to other people". He had developed "strategies to cope with being diagnosed" but was surprised "nobody seems to know why [UC onset] happens. There isn’t a cure for it. They don’t seem to know what causes these flare-ups etc. etc. and all we know is that it’s going to carry on." Conclusion Our interviewee described his symptoms and existing health and healthcare services as stressors, his family and clinicians’ support, his practical, unemotional approach to coping and the need to keep positive. IPA comprehensively captured the interviewee’s interpreted experiences after an UC diagnosis, charting nuanced relationships between stressors, support, and coping. Our study will analyse a further nine individuals’ experiences of stress in the year after an UC diagnosis to inform development of an intervention enhancing resilience to stress.

Exploring the intestinal ecosystem: from gut microbiota to associations with subtypes of inflammatory bowel disease.

Significant differences have been discovered between subtypes of Crohn's disease (CD) and ulcerative colitis (UC). The role of gut microbiota in promoting the onset of UC and CD is established, but conclusions regarding subtype-specific analyses remain limited. This study aims to explore the influence of gut microbiota on subtypes of UC and CD, offering novel insights into the pathogenesis and treatment of UC and CD.Two-sample Mendelian randomization (MR) analysis was employed to examine the causal relationship between subtypes of UC and CD and gut microbiota composition. Gut microbiota data were sourced from the International Consortium MiBioGen, while UC and CD data were obtained from FINNGEN. Eligible single nucleotide polymorphisms (SNPs) were selected as instrumental variables. Multiple analytical approaches such as inverse variance-weighted (IVW), MR-Egger regression, weighted median, weighted mode, and MR-RAPS were utilized. Sensitivity analyses including MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis were conducted for quality control. Subsequently, we employed multivariable IVW, MR-Egger, weighted median, and LASSO regression methods to identify independently significant genera or families and conducted sensitivity analyses. We have determined that Hungatella, Acidaminococcaceae, and 15 other microbial taxa act as protective factors for various CD and UC subtypes, while Terrisporobacter, Anaerostipes, and 23 other microbial taxa are associated with increased risk for different CD and UC subtypes. Furthermore, through multivariable MR analysis, we have identified significant genera or families with independent effects. Our study confirms a causal relationship between dysbiosis of gut microbiota and the occurrence of CD and UC subtypes. Furthermore, it validates etiological distinctions among different subtypes of CD and UC. A novel approach to adjunctive therapy involving distinct UC or CD subtypes may involve the use of probiotics and represents a potential avenue for future treatments.

Preventive effect of lactoferrin peptides on ulcerative colitis

Lactoferrin (LF) plays an essential immunomodulatory role, yet its underlying mechanisms remain unclear. Here, we investigated the suppressive effects of bovine LF and its peptide derivatives (at positions 17–28 of the primary structure) on ulcerative colitis (UC) using a dextran sodium sulphate (DSS)-induced UC mouse model. LF peptides and their amide bodies alleviated DSS-induced colon atrophy. Mice orally administered with LF and its peptides showed decreased epithelial tissue collapse and preserved crypt structure. Additionally, measurement of lipopolysaccharide (LPS) -induced inflammatory cytokine levels in cell culture systems, using macrophage-like RAW264.7, neutrophil-like HL-60, and intestinal epithelium-like Caco-2 cells, suggested the anti-inflammatory effect of LF peptides on intestinal immune function as a possible mechanism underlying LF-induced suppression of UC onset. Thus, LF peptide derivatives may be useful for treating some inflammatory diseases, as the modulatory effect of LF peptide and its amide body was more effective than that of LF.

S3270 Herpes Esophagitis Triggered by Low Dose Steroids During the Initial Induction Therapy for New Onset Ulcerative Colitis

S3270 Herpes Esophagitis Triggered by Low Dose Steroids During the Initial Induction Therapy for New Onset Ulcerative Colitis

Long-term prognosis and clinical practice for new-onset ulcerative colitis in the era of biologics: A Japanese retrospective study.

There is a scarcity of data on long-term outcomes in patients with new-onset ulcerative colitis (UC) in the era of biologics. We aimed to clarify the long-term prognosis of UC and the clinical practice of prescriptions for UC. We collected 6689 new-onset UC cases using a medical claim database provided by DeSC Healthcare, Inc. We investigated the surgery-free, systemic steroid-free, and molecular targeting drug-free rates and compared their differences based on UC-onset age. We used multivariate analysis to identify clinical factors affecting long-term prognosis and investigated the transition of prescriptions for UC. The surgery-free, systemic steroid-free, and molecular targeting drug-free rates at 5 years post-UC diagnosis were 98.5%, 61.0%, and 88.7%, respectively. Pediatric patients had higher surgery-free rates compared with elderly patients and non-pediatric/non-elderly patients (P = 0.022), whereas the systemic steroid-free and molecular targeting drug-free rates were significantly lower (P< 0.0001, P < 0.0001, respectively). The retention rate of the first molecular targeting drug did not differ between drugs. The prescription rates of systemic steroid, immunomodulator, and molecular targeting drug increased from the second quarter in 2014 to the fourth quarter in 2021 (29.8%-39.1%, 6.8%-17.7%, and 7.6%-16.4%, respectively). We clarified the long-term prognosis and clinical practice of new-onset UC cases. The long-term outcome after UC onset might improve because of increasing use of new therapeutic agents. Further investigations are warranted.

Effectiveness of endoscopic resection for colorectal neoplasms in ulcerative colitis: a multicenter registration study

Patients with ulcerative colitis (UC) are at risk of developing colorectal cancer (CRC). The feasibility of endoscopic resection (ER) for UC-associated neoplasia (UCAN) has been suggested, but its efficacy and safety remain unclear. We aimed to assess the efficacy and safety of ER for colorectal neoplasms in patients with UC. This was a retrospective, multicenter cohort study of patients with UC who initially underwent ER or surgery for colorectal neoplasms between April 2015 and March 2021. Patients who had prior colorectal neoplastic lesions were excluded. Among 213 males and 123 females analyzed, the mean age at UC onset was 41.6 years, and the mean age at neoplasia diagnosis was 56.1 years for 240 cases of total colitis, 59 cases of left-sided colitis, 31 cases of proctitis, and 6 cases of segmental colitis. Endoscopic mucosal resection (EMR) was performed for 142 lesions, and endoscopic submucosal dissection (ESD) was performed for 96 lesions. The perforation rate was 2.5% for all 238 lesions removed by ER and 6.3% for the 96 lesions removed by ESD. Among 146 ER lesions followed up with endoscopy, the local recurrence rate was 2.7%. The incidence of metachronous neoplasia after ER was 6.1%. All patients were followed a median of 34.7 months after initial treatment, and 5 died (all surgical cases). Overall survival was significantly higher in the ER group than in the surgery group (P = 0.0085). ER for colorectal neoplasms in UC may be acceptable in selected cases, although follow-up for metachronous lesions is necessary.

Colectomy in patients with ulcerative colitis is not associated to future diagnosis of primary sclerosing cholangitis.

Primary Sclerosing Cholangitis (PSC) is a hepatobiliary disease closely related to ulcerative colitis (UC). In PSC patients, colectomy has been linked to improved prognosis, especially following liver transplantation. This suggests an involvement of the gut-liver axis in PSC etiology. We aimed to investigate the association between colectomy and the risk of future PSC in an epidemiological setting. Through nationwide registers, we identified all adults diagnosed with UC in Sweden 1990-2018 and retrieved information on PSC diagnosis and colectomy. Within the UC cohort (n=61,993 patients), we matched 5577 patients with colectomy to 15,078 without colectomy. Matching criteria were sex, age at UC onset (±5years), year of UC onset (±3years), and proctitis at the time of colectomy. Incidence rates of PSC per 1000-person year were calculated, and the Cox proportional hazard regression model estimated hazard ratios (HRs) for PSC until 31 December 2019. During the follow-up, 190 (3.4%) colectomized UC patients and 450 (3.0%) UC comparators developed PSC, yielding incidence rates of 2.6 and 2.4 per 1000 person-years (HR 1.07 [95% CI 0.90-1.28]). The cumulative incidence of colectomy decreased remarkably over calendar periods, but the cumulative incidence of PSC remained unchanged. The risk of developing PSC in colectomized versus comparators changed over time (HR 0.68 [95% CI; 0.48-0.96] in 1990-97 and HR 2.10 [95% CI; 1.37-3.24] in 2011-18). In UC patients, colectomy was not associated with a decreased risk of subsequent PSC. The observed differences in the risk of PSC development over calendar periods are likely due to changes in PSC-diagnosis and UC-treatment.

The appendix and ulcerative colitis - an unsolved connection.

The appendix is thought to have a role in the pathogenesis of ulcerative colitis, but the nature and basis of this association remains unclear. In this Perspective, we consider the biology of the appendix with respect to its immunological function and the microbiome, and how this relates to evidence that supports the involvement of the appendix in ulcerative colitis. In experimental models, removal of the inflamed appendix prevents colitis, and in human observational studies, appendectomy is associated with protection against ulcerative colitis. Further, among people who develop ulcerative colitis, appendectomy before diagnosis might influence the course and outcomes of the disease - some evidence suggests that it protects against colectomy but could increase the risk of colorectal cancer. Appendectomy after onset of ulcerative colitis seems to have disparate consequences. Clinical trials to understand whether appendectomy has a role in the treatment of ulcerative colitis are ongoing. Major questions about the role of the appendix in the pathogenesis of ulcerative colitis remain unanswered, and further research is needed to establish whether the connection is clinically relevant.

Older patients benefit more from sequential courses of washed microbiota transplantation than younger population with ulcerative colitis

Objectives The short-term efficacy of fecal microbiota transplantation (FMT) for ulcerative colitis (UC) has increasingly been evaluated. However, few studies have examined the long-term efficacy and its predictors. This study aimed to assess the clinical factors affecting the long-term efficacy of FMT for patients with UC. Methods This is a retrospective analysis of a prospective trial (NCT01790061) for patients with UC undergoing washed microbiota transplantation (WMT), which is the improved methodology of FMT. The long-term clinical efficacy of WMT and the factors affecting efficacy were analyzed. Results A total of 259 patients were included for analysis. Of 70.7% (183/259) of patients achieved a clinical response at 1 month after WMT and 29.7% (77/259) achieved steroid-free clinical remission 6 months after WMT. Total 44 patients maintained a clinical response for ≥24 months, and 33 (17.1%, 33/193) achieved steroid-free clinical remission for ≥24 months with WMT monotherapy. Patients with age at UC onset of ≥60 years, mild disease severity and undergoing ≥2 courses of WMT during the response within 6 months were more likely to achieve steroid-free clinical remission 6 months after WMT. Besides, independent factors associated with the long-term response of WMT for UC were age at onset of ≥60 years and ≥2 courses of WMT during the response. Conclusions This study indicated WMT could induce short-term steroid-free clinical remission and maintain long-term response in UC, especially for older patients and patients undergoing sequential courses.

OP30 Human umbilical cord mesenchymal stem cells derived exosomes alleviate Ulcerative Colitis by inhibiting macrophage ferroptosis via miR-23b-3p/Nrf2 pathway

Abstract Background Human umbilical cord mesenchymal stem cell derived exosomes (HucMSC-Exo) have broad application prospects in treatment of various disease, including ulcerative colitis (UC). Macrophages can trigger intestinal mucosal inflammation thereby participating in the onset and development of UC. As a newly discovered iron-dependent cell death pathway, ferroptosis has also been found accompanied by inflammatory response in recent studies. We speculated that there could be relationship between macrophage ferroptosis and inflammatory response in UC. Furthermore, the role of macrophage ferroptosis in the process of HucMSC-Exo alleviating UC remains undefined. This study aims to explore the therapeutic effect and mechanism of HucMSC-Exo on UC by regulating macrophage ferroptosis. Methods The gene expression of ferroptosis-related proteins was assessed in colon samples from healthy controls and UC patients to explore the relationship between ferroptosis and UC. In vivo, colitis was induced by dextran sulfate sodium in mice. HucMSC-Exo was administered intravenously to estimate its curative effect, and its gut homing was evaluated by animal live imaging analysis. In vitro, HucMSC-Exo were cocultured with ferroptosis inducer RSL3-treated bone marrow-derived macrophages (BMDMs), RAW264.7 cell line, followed by examining the effect of HucMSC-Exo. Transfection of microRNA mimics and gene knockdown were used to confirm the role of miR-23b-3p in HucMSC-Exo regulating of macrophage ferroptosis. Results Compared with healthy individuals, ferroptosis may be involved in the mucosal inflammation of UC patients. HucMSC-Exo were found to successfully target damaged colon tissues in vivo. HucMSC-Exo treatment significantly improved the pathological damage of colon tissue, increased the expression of glutathione peroxidase 4 (GPX4), while markedly decreasing the levels of iron and lipid ROS, and reducing the secretion of interleukin (IL)-1β and IL-6, and then relieved macrophage ferroptosis to alleviate murine colitis. In vitro experiments showed that HucMSC-Exo could be effectively absorbed by macrophages and rescued RSL3-induced ferroptosis, which was consistent with the effect of ferrostatin-1, a ferroptosis-specifific inhibitor. Mechanismly, HucMSC-exo could inhibit macrophage ferroptosis by delivering its highly expressed miR-23b-3p to activate Nrf2 pathway. Additionally, the protection of HucMSC-exo for UC was attenuated by decreasing the expression of miR-23b-3p or inhibiting Nrf2 pathway. Conclusion HucMSC-Exo could activate Nrf2 antioxidant pathway and abrogate macrophage ferroptosis by delivering miR-23b-3p and ultimately ameliorate colitis.