Qilian Jiechang Ning (QJN), a traditional Chinese herbal formula, has demonstrated potential therapeutic effects in the treatment of ulcerative colitis (UC). This study aims to investigate the mechanism of QJN in the outer membrane vesicles (OMVs) of Segatella copri (S. copri)-induced colon epithelial cells and UC mice.

Transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) were utilized to assess the morphology and size of OMVs. Inflammation markers and tight junction protein levels in HCoEpiCs induced by OMVs were monitored using ELISA and western blot. QJN was administered to intervene in HCoEpiCs treated with S. copri OMVs. Additionally, trinitrobenzene sulfonic acid (TNBS)-induced mouse models were conducted to evaluate the therapeutic effects of QJN on UC.

S. copri OMVs treated with QJN demonstrated a significant reduction in particle size, protein concentration, and LPS content. In HCoEpiCs, QJN effectively decreased the expression of inflammation-inducing cytokines (IL-1β, IL-18, IL-6, TNF-α) and proinflammatory proteins (GSDMD-N, NLRP3, ASC, cleaved Caspase-1, cleaved Caspase-4) triggered by S. copri OMVs, while enhancing the expression of tight junction proteins (ZO-1 and Occludin). In the UC mouse models, QJN significantly reduced the Disease Activity Index (DAI), improved colon length, lowered LPS levels, ameliorated colonic tissue damage, and inhibited Caspase-1- and Caspase-11-dependent inflammatory responses.

QJN can alleviate S. copri-OMV-induced inflammatory response in colonic epithelial cells and reduce symptoms of UC in mouse models by modulating the Caspase-1 and Caspase-11 pathways.

Data suggests 5-Aminosalicytes (5-ASA) medication does not influence outcomes in patients with moderate to severe ulcerative colitis (UC) on advanced therapy and can be discontinued. However, patients' perspectives on discontinuing UC-related medications have not been evaluated and should be incorporated when considering therapy changes. This study explored patients' experiences with UC treatment (5-ASA) in combination with advanced therapy, and barriers, facilitators, and attitudes toward deprescribing 5-ASAs.

To qualitatively evaluate patients' views on 5-ASA medication discontinuation two focus groups were conducted for patients with UC on stable doses of 5-ASA medication and advanced therapy for at least 6 months. Patients were asked about their satisfaction with and barriers to current therapy, quality of life, and opinions about the potential medication deprescribing. Transcripts were analyzed using an iterative inductive/deductive approach.

Ten patients participated with an average age 50 years (SD ± 11 years), 50% Female, and 80% White. Advanced therapy included tofacitinib (20%), vedolizumab (20%), or infliximab (20%). Qualitative analysis identified patient and clinician factors in the deprescribing process. Patient themes included emotions and coping, quality of life, attitudes and beliefs, experiences with the condition, and symptoms. Participants identify clinician themes including endorsement, communication, patient relationship, information distribution, and deprescribing readiness for change. The shared patient/clinician risk assessment was vital to moving towards deprescribing, however the decision to deprescribe was influenced by barriers and facilitators including further discussion with their clinician.

Patients with UC on advanced therapy and 5-ASA are open to deprescribing their 5-ASA but would have questions for their prescribing clinician including assurance of continued symptom management or ease of returning to the 5-ASA if needed.

Several therapeutic advances have been achieved over the past two decades for inflammatory bowel disease (IBD). The expanding therapeutic armamentarium and the increasingly ambitious treatment targets have led to an increased use of advanced therapies and better outcomes. Nevertheless, many patients remain suboptimally treated and are at risk of disease progression, hospital admission, and surgery, even when advanced therapies are cycled, escalated, or combined. Conversely, IBD can also be characterised by an indolent disease course. Top-down and treat-to-target strategies, although beneficial in a substantial proportion of patients, might not be advantageous in patients with mild disease and might risk overtreatment. Identifying patients with mild activity and a benign disease trajectory in the long-term is important; unnecessary exposure to advanced therapies increases the risk of adverse events and increases financial costs and health-care resource utilisation. This Review details the importance of adopting clinical strategies to avoid the pitfalls of undertreating and overtreating IBD.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by continuous inflammation of the colon and rectum. Accurate disease assessment is essential for effective treatment, with endoscopic evaluation, particularly the Mayo Endoscopic Score (MES), serving as a key diagnostic tool. However, MES measurement can be subjective and inconsistent, leading to variability in treatment decisions. Deep learning approaches have shown promise in providing more objective and standardized assessments of UC severity.

This study utilized publicly available endoscopic images of UC patients to analyze and compare the performance of state-of-the-art deep neural networks for automated MES classification. Several state-of-the-art architectures were tested to determine the most effective model for grading disease severity. The F1 score, accuracy, recall, and precision were calculated for all models, and statistical analysis was conducted to verify statistically significant differences between the networks.

VGG19 was found to be the best-performing network, achieving a QWK score of 0.876 and a macro-averaged F1 score of 0.7528 across all classes. However, the performance differences among the top-performing models were very small suggesting that selection should depend on specific deployment requirements.

This study demonstrates that multiple state-of-the-art deep neural network architectures could automate UC severity classification. Simpler architectures were found to achieve competitive results with larger models, challenging the assumption that larger networks necessarily provide better clinical outcomes.

In inflammatory bowel disease, protein misfolding in the endoplasmic reticulum (ER) potentiates epithelial barrier dysfunction and impairs mucosal healing. Tauroursodeoxycholic acid (TUDCA), a naturally occurring bile acid, acts as a chemical chaperone to reduce protein aggregation and colitis severity in preclinical models. We conducted an open label trial evaluating oral TUDCA as therapy in patients with active ulcerative colitis (UC).

Patients with moderate-to-severely active UC (Mayo score ≥6, endoscopic subscore ≥1) received oral TUDCA at 1.75 or 2 g/day for 6 weeks. Exclusion criteria included known hepatic disorders or change in UC therapy within 60 days. Clinical disease activity questionnaires, endoscopy with biopsy, blood, and stool were collected at enrollment and after 6 weeks. The primary outcome measure was change in ER stress markers while safety, tolerability and change in UC disease activity were secondary outcomes.

Thirteen participants completed the study with eleven evaluable for clinical response. TUDCA was well-tolerated with transient dyspepsia being the most common side effect. Mucosal biopsies revealed significant reductions in ER stress and inflammation as well as an increase in markers of epithelial restitution. Clinical, endoscopic, and histologic disease activity were significantly improved at week 6 (mean total Mayo Score: 9 to 4.5, p<0.001).

Six weeks of oral TUDCA treatment was well-tolerated in patients with active ulcerative colitis and promoted mucosal healing, lessened ER stress, and reduced clinical disease activity. A randomized controlled trial of adjunctive TUDCA therapy in patients with UC is warranted.

ClinicalTrials.gov (NCT04114292).

Individuals with ulcerative colitis (UC) are frequently re-hospitalized for persistent or recurrent severe disease flares. Accurate prediction of the risk of early re-hospitalization at the time of discharge could promote targeted outpatient interventions to reduce this risk.

We conducted a retrospective study in adults with UC admitted to The Ottawa Hospital between 2009 and 2016 for an acute UC-related indication. We ascertained candidate demographic, clinical, and health services predictors through medical records and administrative health databases. We derived and bootstrap validated a multivariable logistic regression model of 90-day UC-related re-hospitalization risk. We chose a probability cut point that maximized Youden's index to differentiate high-risk from low-risk individuals and assessed model performance.

Among 248 UC-related hospitalizations, there were 27 (10.9%) re-hospitalizations within 90 days of discharge. Our multivariable model identified gastroenterologist consultation within the prior year (adjusted odds ratio [aOR] 0.11, 95% confidence interval [CI], 0.04-0.39), male sex (aOR 3.27, 95% CI, 1.33-8.05), length of stay (OR 0.94, 95% CI, 0.88-1.01), and narcotic prescription at discharge (OR 1.96, 95% CI, 0.73-5.27) as significant predictors of 90-day re-hospitalization. The optimism-corrected c-statistic value was 0.78, and the goodness-of-fit test P-value was .09. The chosen probability cut point produced a sensitivity of 77.8%, specificity of 80.9%, positive predictive value (PPV) of 33.0%, and negative predictive value (NPV) of 96.7% in the derivation cohort.

A limited set of variables accessible at the point of hospital discharge can reasonably discriminate re-hospitalization risk among individuals with UC. Future studies are required to validate our findings.

Clinical guidelines typically endorse conventional therapies such as 5-aminosalicylic acid (5-ASA) as the mainstay of ulcerative colitis management. However, the degree of adoption and application of guideline recommendations by physicians within Asia remains unclear. This study aims to understand the prescribing patterns of 5-ASA and implementation of current guideline recommendations across Asian clinical practice. A physician survey was conducted among inflammatory bowel disease specialists in 8 Asian territories to understand practices and preferences in ulcerative colitis management, focusing on the use of 5-ASA and concordance with guideline recommendations. Survey findings were validated by country experts in diverse healthcare settings. Subgroup analyses stratified data by income levels and treatment reimbursement status. Ninety-eight valid responses were received from inflammatory bowel disease specialists or gastroenterologists among 8 economic entities. Significant differences were found in clinical practices and treatment preferences for ulcerative colitis management among different income-level and government-subsidy groups. Survey results are summarized in 8 findings that illustrate trends in 5-ASA use and guideline implementation across Asian territories. This study emphasizes socioeconomic factors that impact the adoption of guideline recommendations in real-world practice. Our findings indicate an eclectic approach to guideline implementation across Asia, based on resource availability and feasibility of treatment goals.

Targeted immunomodulators (eg, advanced therapies) effectively achieve symptomatic remission in patients with inflammatory bowel disease (IBD). However, ~25%-50% of patients with IBD achieving symptomatic remission with an advanced therapy may have continued endoscopically/radiologically active bowel inflammation, and it is uncertain whether changing alternative advanced therapies in asymptomatic patients with IBD will reduce bowel inflammation and achieve durable deep remission.

The QUality Outcomes Treating IBD to Target (QUOTIENT) study is an open-label, multicentre, pragmatic, randomised, controlled trial that aims to compare the efficacy and safety of switching to an alternative advanced therapy targeting endoscopic/radiological remission (treat-to-target) versus continuing the initial, or index, advanced therapy, in asymptomatic patients with IBD with moderate-to-severe endoscopic/radiological bowel inflammation. Enrolment is planned for ~250 participants in Canada/USA, randomised 1:1 to switching to alternative advanced therapy or continuing index advanced therapy, and then followed 104 weeks within routine clinical practice. Patient-reported outcomes measure efficacy and quality of life/treatment burden/safety. Primary endpoint is the time from randomisation to treatment failure.

The study is conducted in compliance with the protocol, ICH Good Clinical Practice, applicable regulatory requirements and appropriate review boards/independent ethics committees (approval numbers: Pro00077486; Pro00061437; STUDY00002062; 22-004171; i22-01269; IRB22-0890; IRB_00154397; 2000032384; SHIRB#2022.095-2; STUDY00007146; MMC#2024-18; REB#125290; 17784; Pro00142214; 20240660-01H), with documented written informed consent. Findings will be disseminated through peer-reviewed journals, scientific presentations, and publicly available Patient-Centered Outcomes Research Institute (PCORI) websites, including lay summaries. The Crohn's & Colitis Foundation Education, Support, and Advocacy Department, and our patient advocacy stakeholder, will develop educational and marketing resources to communicate findings to a broad audience (>250 000 patients/caregivers/healthcare professionals).

NCT05230173.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by chronic inflammation of the colonic mucosal lining.

This study aimed to examine unmet needs among patients with UC in Spain.

Data were analyzed from the Adelphi Real World IBD Disease Specific Programme™, a cross-sectional survey of physicians and patients with IBD in Spain between October 2020 and March 2021.

Physicians reported patient clinical characteristics, disease severity, treatment patterns and satisfaction, symptoms, and flare and remission status. Patients were then invited to voluntarily self-complete a form reporting health-related quality of life (HRQoL) and work productivity/activity impairment. Analyses were descriptive.

Overall, 57 physicians reported data for 410 patients with UC presenting a high disease severity profile. The mean (standard deviation) patient age was 45 (15) years, with 88% presenting with moderate-to-severe UC at diagnosis. In the survey, 75% and 63% of patients were treated with conventional therapy and biologics, respectively. After treatment initiation, patients had lower disease severity, but 29% of patients had moderate-to-severe disease despite receiving biologics or Janus kinase inhibitors. Overall, 81% of patients and 86% of physicians were satisfied with treatment. Among patients classified as having moderate-to-severe UC, commonly reported symptoms included abdominal pain (41%), bowel urgency (37%), and bloody diarrhea (37%). The mean number of flares experienced in the past year was 1.7, lasting on average >30 days. Consequently, the HRQoL of these patients was impaired.

While disease severity appeared to be lower after the initiation of current treatment, and despite the high prevalence of treatment satisfaction, almost a third of patients remained classified as moderate-to-severe, experiencing symptoms, flares, and impaired HRQoL. Therefore, there is a need for new therapeutic alternatives to target patient unmet needs.

Inflammatory bowel disease (IBD) is a chronic condition that includes two main types, Crohn's disease (CD) and ulcerative colitis (UC), involving inflammation of the gastrointestinal (GI) tract. The exact cause of IBD is unknown but could be a combination of genetic, environmental, and immune system factors. This study investigated the impact of IBD on microbiota diversity by evaluating the differences in microbial composition and the microbiota of a control group (A) of healthy individuals and a group (B) of IBD patients. Sixty biopsies were collected from participants recruited from hospitals in Makkah, Saudi Arabia. Biopsy specimens were taken during colonoscopy examination, and bacterial identification was performed by extracting ribosomal DNA from sigmoid colon biopsies using a DNeasy Blood & Tissue Kit. Metagenomics and bioinformatics analyses were then conducted to analyze and compare the microbiota in the two groups. The results showed that the varieties of core microbiome species were 3.81% greater in the IBD patients than in the members of the control group. Furthermore, the differences between the groups were significantly greater than the variations within each group. Differences between the two groups were detected in the relative abundance of Clostridium nexile, Ruminococcus gnavus, Ruminococcus faecis, and Escherichia coli. These results indicate that microbiota could play a role in the pathogenesis of IBD and suggest that microbial diversity can serve as a biomarker for diagnosing the disease and monitoring its progression.

Daifu Decoction (DFD), a patented herbal prescription used to prevent and treat ulcerative colitis (UC). This study aimed to reveal the effect of DFD on the relapse of UC and its mechanism via integrated retrospective clinical analysis, network pharmacology and in vivo and in vitro experimental validation.

First, the clinical data of UC patients treated with DFD were reviewed from a real-world study (RWS), and the relapse at 24 weeks after drug withdrawal was recorded to evaluate the relapse rate. Next, the chemical components of DFD were identified via ultra performance liquid chromatography‒mass spectrometry (UPLC‒MS), and the differentially expressed genes (DEGs) between UC patients in the active and remission stages were screened as disease targets related to the relapse of UC from the Gene Expression Omnibus (GEO) database. The core components, targets and key signalling pathways of DFD for preventing the relapse of UC were discussed via network pharmacology. Finally, the above results were verified via molecular docking and in vivo and in vitro experiments.

A total of 475 UC patients were included, and the relapse rate of UC treated with DFD was 23.9%. Additionally, the 221 components identified by UPLC-MS and 398 DEGs related to the relapse of UC enriched the main pathway of the relapse of UC was IL-17 signaling pathway and the inflammatory-related targets, such as IL6, PTGS2, MMP7, MMP3, MMP1. Moreover, molecular docking revealed that the core components of DFD were able to bind to inflammation-related targets, and in vivo and in vitro experiments demonstrated that DFD could inhibit the IL-17 pathway, increase the level of claudin-1, and control inflammation to prevent UC relapse.

DFD can effectively prevent the relapse of UC which may be related to inhibiting the activation of IL-17 signalling pathway.

Many patients with inflammatory bowel disease (IBD) experience treatment failures despite availability of effective advanced biologic and small-molecule therapies with differing mechanisms of action. Dual biologic therapy (DBT) is being explored to improve efficacy outcomes and address unmet needs in this difficult-to-treat population. This study aimed to understand patient preferences for DBT efficacy and risk tolerance.

Built on evidence from existing treatment-preference studies, a focused discrete-choice experiment (DCE) was developed to measure preferences for treatment type, chance of remission, and risk of serious infection. Individuals with a physician-verified diagnosis of Crohn's disease or ulcerative colitis who had failed or were taking advanced therapy were recruited through an IBD registry. DCE responses were analyzed using a fully correlated random parameters logit model.

The DCE survey was completed by 280 respondents. The majority of respondents were White, female; had been previously hospitalized for IBD; and were receiving biologic monotherapy for their IBD disease. There was no meaningful difference in preference for DBT or monotherapy (P = 0.25), while there was strong preference to avoid corticosteroids (P < 0.001). To improve from a 50% to 70% in chance of remission, respondents would accept up to a 17.5% (95% confidence interval 17.0%-18.0%) risk of serious infection.

The findings suggest that patients prefer safe and efficacious treatments and DBT may be an acceptable option for those who have failed an advanced therapy for IBD. We demonstrate the value of building on existing evidence and designing efficient DCE studies to address knowledge gaps to improve IBD care.

Data on predictors of complicated ulcerative colitis (UC) course from unselected populations cohorts are scarce. We aimed to utilize a nationwide cohort to explore predictors at diagnosis of disease course in children and adults with UC.

Data of patients diagnosed with UC since 2005 were retrieved from the nationwide epi-IIRN cohort. Complicated disease course was defined as colectomy, steroid-dependency, or the need for biologic drugs. Hierarchical clustering categorized disease severity at diagnosis based on complete blood count, albumin, C-reactive protein and erythrocyte sedimentation rate (ESR), analyzed together.

A total of 13 471 patients with UC (1427 [11%] pediatric-onset) including 103 212 person-years of follow-up were included. Complicated disease course was recorded in 2829 (21%) patients: 1052 (7.9%) escalated to biologics, 1357 (10%) experienced steroid-dependency, and 420 (3.1%) underwent colectomy. Probabilities of complicated disease course at 1 and 5 years from diagnosis were higher in pediatric-onset (11% and 32%, respectively) than adult-onset disease (4% and 16%; P < .001). In a Cox multivariate model, complicated course was predicted by induction therapy with steroids (hazard ratio [HR], 1.5; 95% CI, 1.2-2.0), extraintestinal manifestations (HR, 1.3; 95% CI, 1.03-1.5) and the disease severity clusters of blood tests (HR, 1.8; 95% CI, 1.01-3.1), while induction therapy with enemas (HR, 0.6; 95% CI, 0.5-0.7) and older age (HR, 0.99; 95% CI, 0.98-0.99) were associated with noncomplicated course.

In this nationwide cohort, the probability of complicated disease course during the first 5 years from diagnosis was 32% in pediatric-onset and 16% in adults with UC and was associated with more severe clusters of routinely collected laboratory tests, younger age at diagnosis, extraintestinal manifestations, and type of induction therapy.

The performance of endoscopic evaluation of ulcerative colitis (UC) using conventional scoring, including Mayo endoscopic subscore (MES) and ulcerative colitis endoscopic index of severity (UCEIS), is not satisfactory. Recently, the usefulness of novel image-enhanced endoscopy (IEE) such as texture and color enhancement imaging (TXI) and red dichromatic imaging (RDI) has been reported in the endoscopic evaluation of UC. We evaluated the performance of IEEs in UC, particularly focusing on the correlation with MES and UCEIS, and prediction of relapse.

This is a prospective, observational study. UC patients in clinical remission who underwent colonoscopy with evaluation of IEEs and follow-up for > 3 months were analyzed. TXI and RDI were evaluated using the previously reported scoring system (TXI 0-2 and RDI 1-4). The IEE scores were compared with the conventional scoring, fecal calprotectin levels, and histological findings using Geboes score, and patient's clinical relapse rate stratified by each IEE score was examined.

Both TXI and RDI scores were well-correlated with MES and UCEIS (both p < 0.001), fecal calprotectin levels (p = 0.015 and p = 0.006), and histology evaluated with Geboes score. In the Geboes subscore, the subscore 2B (neutrophil infiltration in lamina propria) was the most correlated with each endoscopic scoring. RDI 3-4 was significantly correlated with subsequent relapse (hazard ratio 3.56, 95% confidence interval 1.13-11.24), but TXI scoring did not predict relapse significantly.

The assessment using RDI could be a convenient and useful endoscopic evaluation method for predicting the prognosis of UC.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) characterised by episodes of symptoms including rectal bleeding, increased stool frequency and abdominal pain, impacting quality of life significantly. Conventional treatments often come with potential side effects and may not be sufficient. Acupuncture is increasingly recognised for its potential benefits in UC. This study aims to assess the efficacy and safety of acupuncture for symptom relief in mild to moderate UC.

This single-centre, parallel-arm, randomised, sham-controlled, the two-step acupuncture (TSA)-UC trial, will involve 64 adults with mild to moderate UC, randomly assigned in a 1:1 ratio to either the acupuncture or sham acupuncture group. Participants will receive 20 sessions of two-step acupuncture or sham acupuncture therapy over 8 weeks. Blinding will be applied to participants, outcome assessors and statisticians. The primary outcome measure is the change in Patient-Reported Outcome 2 (PRO2) from baseline at week 8. Secondary outcomes include changes from baseline in the following scales: PRO2 at other time points, weekly average Numeric Rating Scale (NRS) for bowel urgency, weekly average NRS for abdominal pain (both associated and not associated with bowel movement), the 32-item Inflammatory Bowel Disease Questionnaire, Work Productivity and Activity Impairment Questionnaire-IBD, Pittsburgh Sleep Quality Index and Hospital Anxiety and Depression Scale. The Patient Global Impression of Change will also be assessed. Long-term effects of acupuncture will be explored. Adverse events and additional treatments will be monitored throughout the study. The modified intention-to-treat population including participants who complete baseline assessments and receive at least one treatment session will be analysed.

The study has received ethical approval from the Ethics Committee of Guang'anmen Hospital, China Academy of Chinese Medical Sciences (2024-190-KY). The results will be published in a peer-reviewed medical journal.

NCT06615765.

Patients with long-standing inflammatory bowel disease (IBD) involving the colon are at higher risk of developing colorectal dysplastic or neoplastic lesions. While from sporadic colorectal cancer follows an "adenoma-carcinoma" sequence, IBD colitis-associated carcinogenesis is mainly related to an "inflammation-dysplasia-carcinoma" sequence. Currently, specific endoscopic surveillance strategies involving dye spray and virtual chromoendoscopy have been standardized, aiming for early CRC diagnosis. When detected, colitis-associated dysplasia should be classified according to standard classification, thus allowing for better treatment. Indeed, most IBD-associated dysplastic lesions can be treated with endoscopic resection, even though available procedures are usually more challenging than those in the general population. The higher frequency of severe submucosal fibrosis and the difficulty in the definition of lesions' margins account for this issue. Current endoscopic resection techniques include polypectomy, endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). Recent evidence suggests the relevance of en bloc resection, as this may be associated with lower rates of recurrence. Therefore, particularly for larger (>20 mm) lesions, ESD should be preferred, even though it is considered the most difficult technique due to frequent severe submucosal fibrosis. Considering the growing number of new endoscopic resective techniques, including underwater EMR or ESD, which in the general population have been suggested to lower procedure-related risks and may also allow a larger spread of advanced endoscopic resection in IBD. However, additional data are needed to assess the medium- and long-term efficacy of endoscopic resection of visible dysplasia in IBD patients, which are burdened by a high risk of local and, more importantly, metachronous recurrence.

TongXieYaoFang (TXYF), a classical formula used in Traditional Chinese Medicine, is renowned for its efficacy in treating chronic abdominal pain and diarrhoea. Modern research suggests that fundamental relief from these symptoms depends on complete intestinal mucosal healing, which normalises gut secretory functions. Consensus between traditional and modern medical theories indicates that TXYF is particularly suitable for treating the remission phase of ulcerative colitis (UC). Unfortunately, its potential in the remission phase has not received sufficient attention, and its use has been largely limited to a supportive role during the acute phase.

This study aimed to elucidate the efficacy of TXYF in promoting intestinal mucosal healing and enhancing gut secretory function during the non-acute damage phase, as well as to identify the underlying mechanisms contributing to its effects.

A mouse model of dextran sulphate sodium salt (DSS)-induced colitis was optimised to specifically evaluate the effects of TXYF on mucosal healing during the repair phase. The effects of TXYF on murine colon function were assessed by measuring faecal pellet count and water content, and further evaluated through immunohistochemical analyses. The underlying mechanisms of action of TXYF were elucidated using mouse intestinal organoid cultures, intestinal stem cell (ISCs) transplantation, immunofluorescence, and western blotting. Active components of TXYF were identified via LC-MS/MS analysis and integrated with network pharmacology for bioinformatics assessment.

TXYF significantly promoted mucosal healing, as reflected by reduced disease activity scores, increased colon length, enhanced epithelial proliferation, and decreased histological damage. Furthermore, TXYF enhanced the recovery of critical intestinal functions, including barrier integrity, absorption, secretion, and motility. Notably, the improvement in the secretory function was particularly pronounced. Mechanistically, these therapeutic effects were mediated by the upregulation of the Atonal homolog 1/SAM pointed domain containing ETS transcription factor/Mucin 2 pathway, which facilitates the differentiation and maturation of ISCs into goblet cells, thereby contributing to both mucosal repair and enhanced secretory function.

Our study demonstrated that TXYF significantly promotes intestinal mucosal healing and enhances secretory function. These findings offer a solid basis for exploring the potential applications of TXYF in UC management during the remission phase.

Despite a growing armamentarium of medical therapies for ulcerative colitis, colectomy remains an important therapeutic option. To better inform shared decision-making about surgery, we estimated the contemporary risk of mortality after colectomy.

Mortality rates were estimated using the National Inpatient Sample (2016-2020). Factors associated with postcolectomy death were evaluated in multivariable regression.

Postcolectomy mortality occurred in 1.2% (95% CI: 0.8%, 1.9%) of hospitalizations. Comorbidity burden, emergent laparotomy, and delays to surgery >5 days after admission were associated with mortality.

Colectomy may be associated with mortality; however, this risk is heterogeneous based on patient- and procedural-related factors.

The multidrug resistance 1 (MDR1) gene is a gene involved in the pathogenesis of inflammatory bowel disease (IBD).The aim of the study is to investigate the association of MDR-1 gene polymorphisms (C2345T and G2677T) and IBD incidence in Egyptian patients, and its relation with disease severity.

This is a case-control study where genotyping of MDR-1 gene C3435T and G2677T single nucleotide polymorphisms (SNPs) were assayed.

Forty naïve IBD patients, who were composed of 25 UC and 15CD, were compared to 60 healthy controls. They were young aged with significant female predominance, particularly in CD (P = 0.004). UC was mainly (48 %) presented in moderate severity while CD was mainly (53.3 %) presented with mild severity. MDR-1 gene C3435T SNP was not statistically related to IBD, whether in terms of genotypes or alleles, yet its T allele was significantly related to moderate cases of UC (P = 0.014). However, GG genotype of G2677T SNP was significantly low in IBD (P = 0.013), while TT genotype and T allele were significantly related to CD (P = 0.011, and 0.012 respectively). Moreover, G allele proved to be associated significantly with moderate cases of UC (P = 0.001) and mild cases of CD (P = 0.002).

MDR-I gene G2677T SNP GG genotype proved to be protective against IBD, thus may be considered in diagnostic workup of IBD including its severity.

Background/Aims: Numerous patients with ulcerative colitis (UC) become mentally unstable after experiencing a long-standing, physically painful life, and their long-term prognosis is poorer than that of those who are mentally stable. The current study aimed to evaluate serum biomarkers for predicting mental instability, which is challenging to objectively quantify. Methods: In total, 29 refractory UC patients newly treated with filgotinib underwent measurements of blood parameters associated with depression and a quantitative assessment of quality of life using the Inflammatory Bowel Disease Questionnaire (IBDQ) before and after treatment initiation with a 12-week interval. The data collected were examined in relation to each other. Results: The induction of remission treatment with filgotinib resulted in a clinical response rate of 89.7% and a clinical remission rate of 86.2%, with all eight extraintestinal manifestations resolved. No adverse events were observed. The serum zinc, high-density lipoprotein cholesterol, mature brain-derived neurotrophic factor (BDNF) concentrations, and the IBDQ psychiatric subscores increased significantly after treatment (p < 0.05). Among these parameters, the mature-BDNF concentration and the IBDQ psychiatric subscore had the strongest positive correlation (R = 0.29, p = 0.08). Based on the logistic regression analysis, the mature-BDNF concentration (cutoff value: 20.5 ng/mL) had a sensitivity of 68.2%, specificity of 64.7%, and area under the curve of 0.67 for predicting psychiatric remission (subscore > 42.5) (p = 0.04). Conclusions: While it is not easy to objectively predict the degree of psychiatric instability in patients with refractory UC, serum mature-BDNF levels can be a useful biomarker.

Last decades led to a revolution in the management of ulcerative colitis (UC), due to the development of novel advanced therapies and the identification of increasingly ambitious therapeutic goals. Nevertheless, a subset of patients, refractory to available therapies, still requires proctocolectomy with ileal pouch-anal anastomosis (IPAA). Pouchitis, an inflammatory condition of the ileal pouch, is the most common long-term complication of IPAA, affecting almost one-half of patients in the first 10 years after surgery. Symptoms of pouchitis include increased stool frequency, urgency, and abdominal discomfort, significantly affecting patients' quality of life. Traditionally the mainstay treatment of acute pouchitis involves the use of antibiotics, but one-fifth of patients develop chronic pouchitis (CP), which may be dependent or resistant to antibiotics, posing significant challenges in the management of this condition. Currently, there is still no consensus on the optimal management for CP, though recent progress in understanding the pathophysiology of pouchitis has paved the way for innovative therapeutic approaches, based on biological therapies and small molecules. This review aims to discuss the recent advanced therapies available for pouchitis and provide a comprehensive review on the topic to guide physicians in their clinical practice.

There is insufficient evidence comparing the outcomes of tacrolimus-based remission induction therapy with infliximab in refractory ulcerative colitis (UC) and evidence regarding optimal strategies after tacrolimus-based remission induction therapy. We conducted a multi-institutional retrospective study of patients with UC treated with tacrolimus or infliximab between January 2010 and March 2019. The proportion of clinical remission at week 8 and cumulative colectomy-free rate were examined using propensity score matching analysis. The predictors for colectomy after tacrolimus induction were also investigated. Ninety patients in the tacrolimus group and 151 in the infliximab group were enrolled. The proportion of patients in clinical remission at week 8 was 65.2% in the matched tacrolimus group and 37.3% in the matched infliximab group (P = 0.0016), and the long-term colectomy-free rate was lower in the matched tacrolimus group than in the matched infliximab group (P = 0.0003). After clinical remission with tacrolimus, a serum albumin level of ≤ 3.5 g/dL at week 8 was extracted as a factor predicting colectomy (area under the curve: 0.94). Tacrolimus showed a higher remission induction effect for UC compared to infliximab. However, a high rate of colectomy after transition to maintenance treatment was found to be a concern for tacrolimus therapy.

The lack of clear definition and classification for "moderate ulcerative colitis (UC)" creates ambiguity regarding the suitability of step-up versus top-down treatment approaches. In this paper, experts address crucial gaps in assessing and managing moderate UC. The Asia-Pacific, Middle East, and Africa Inflammatory Bowel Disease Coalition comprised 24 experts who convened to share, discuss and vote electronically on management recommendations for moderate UC. Experts emphasized that the goal of treating UC is to attain clinical, biomarker, and endoscopic remission using cost-effective strategies such as 5-aminosalicylates (5-ASAs), well-tolerated therapy that can be optimized to improve outcomes. Experts agreed that 5-ASA therapy could be optimized by maximizing dosage (4 g/day for induction of remission), combining oral and topical administration, extending treatment duration beyond 8 weeks, and enhancing patient adherence through personalized counselling and reduced pill burden. Treatment escalation should ideally be reserved for patients with predictors of aggressive disease or those who do not respond to 5-ASA optimization. Premature treatment escalation to advanced therapies (including biologics and oral small molecules) may have long-term health and financial consequences. This paper provides consensus-based expert recommendations and a treatment algorithm, based on current evidence and practices, to assist decision-making in real-world settings.

Recent therapeutic innovations in the management of inflammatory bowel disease (IBD) have significantly improved patient outcomes, leading to increased life expectancy and reducing the necessity for total colectomy. However, this prolonged disease duration increases the cumulative risk for dysplasia and eventually colorectal cancer development. Therefore, timely detection and correct characterization of emerging dysplastic lesions is of great importance in longstanding IBD. This narrative review aims to elucidate the current state of advanced endoscopic imaging for dysplasia characterization in inflammatory bowel disease.

This study aims to clarify angiogenesis mechanisms in ulcerative colitis and identify potential therapeutic targets.

The Gene Expression Omnibus (GEO) database was used to obtain expression profiles and clinical data for UC and healthy colon tissues. Angiogenesis-related gene sets were acquired from GeneCards. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) identified UC-associated hub genes. The CIBERSORT algorithm assessed immune cell infiltration. Analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to determine biological mechanisms. External datasets were utilized to validate and characterize the angiogenesis-related genes in relation to biological agents. Additionally, an ulcerative colitis mouse model was constructed to verify the key genes' expression using real-time quantitative PCR. To predict potential therapeutic agents, we used the DGIdb database. Molecular docking modeled small molecule binding conformations to key gene targets.

This study identified 1,247 DEGs enriched in inflammatory/immune pathways from UC and healthy colon samples. WGCNA indicated the black and light cyan modules were most relevant. Intersecting these with 89 angiogenesis genes revealed 5 UC-associated hub genes (pdgfrb, vegfc, angpt2, tnc, hgf). Validation via ROC analysis, differential expression, and a mouse model confirmed upregulation, supporting their potential as UC diagnostic biomarkers. Bioinformatics approaches like protein-protein interaction, enrichment analysis, and GSEA revealed involvement in PDGFR and PI3K-Akt signaling pathways. CIBERSORT analysis of immune cell infiltration showed positive correlations between the key genes and various immune cells, especially neutrophils, highlighting angiogenesis-inflammation interplay in UC. A ceRNA network was constructed. Drug prediction and molecular docking revealed potential UC therapies like sunitinib and imatinib targeting angiogenesis.

This study identified and validated five angiogenesis-related genes (pdgfrb, vegfc, angpt2, tnc, hgf) that may serve as diagnostic biomarkers and drug targets for UC.

We aimed to investigate the characteristics of pediatric ulcerative colitis (UC) at diagnosis in Korea.

This was a multicenter, registry-based, inception cohort study conducted in Korea between 2021 and 2023. Children and adolescents newly diagnosed with UC < 18 years were included. Baseline clinicodemographics, results from laboratory, endoscopic exams, and Paris classification factors were collected, and associations between factors at diagnosis were investigated.

A total 205 patients with UC were included. Male-to-female ratio was 1.59:1, and the median age at diagnosis was 14.7 years (interquartile range 11.9-16.2). Disease extent of E1 comprised 12.2% (25/205), E2 24.9% (51/205), E3 11.2% (23/205), and E4 51.7% (106/205) of the patients. S1 comprised 13.7% (28/205) of the patients. The proportion of patients with a disease severity of S1 was significantly higher in patients with E4 compared to the other groups (E1: 0% vs. E2: 2% vs. E3: 0% vs. E4: 24.5%, P < 0.001). Significant differences between disease extent groups were also observed in Pediatric Ulcerative Colitis Activity Index (median 25 vs. 35 vs. 40 vs. 45, respectively, P < 0.001), hemoglobin (median 13.5 vs. 13.2 vs. 11.6 vs. 11.4 g/dL, respectively, P < 0.001), platelet count (median 301 vs. 324 vs. 372 vs. 377 × 10³/μL, respectively, P = 0.001), C-reactive protein (median 0.05 vs. 0.10 vs. 0.17 vs. 0.38 mg/dL, respectively, P < 0.001), and Ulcerative Colitis Endoscopic Index of Severity (median 4 vs. 4 vs. 4 vs. 5, respectively, P = 0.006). No significant differences were observed in factors between groups divided according to sex and diagnosis age.

This study represents the largest multicenter pediatric inflammatory bowel disease cohort in Korea. Disease severity was associated with disease extent in pediatric patients with UC at diagnosis.

Clinical Research Information Service Identifier: KCT0008723.

The inflammatory bowel diseases (IBDs), ulcerative colitis (UC) and Crohn's disease (CD), are heterogenous diseases ranging from mild to severe. We aimed to describe the prevalence and prognosis of mild IBD in an unselected population-based patient cohort.

We identified all individuals diagnosed with IBD during 1997 to 2020 in North Denmark (n = 4607). Patients with mild disease, based on treatment history within the first year, were followed for progression to moderate-severe disease, based on a composite outcome of immunomodulators, biologic therapies, IBD-related hospitalization, and/or surgery. We used time-to-event analysis to calculate probabilities of progression based on IBD subtype, age, sex, and duration of mild IBD.

Among 2315 individuals with initial mild IBD, 24.5% with UC (n = 474) and 46% with CD (n = 174) progressed to moderate-severe disease during follow-up. Of the total IBD population, 52.3% of patients with UC and 86.8% with CD progressed during follow-up. Individuals <18 years at diagnosis were the most likely to progress. The 10-year probability of progressing to moderate-severe UC was 26% after 1 year with mild disease, 19% after 5 years, and 12% after 10 years. The probability of progressing to moderate-severe CD was 53% after 1 year with mild disease, 34% after 5 years, and 33% after 10 years.

Approximately one-fourth of individuals with mild UC within 1 year after diagnosis and one-half of those with mild CD progressed to moderate-severe disease over time. Young age at diagnosis increased the probability of progression, whereas increasing duration of mild disease decreased the probability.

Fecal calprotectin (FC) is a promising biomarker for assessing ulcerative colitis (UC) endoscopic activity. However, the optimal FC cutoff to identify each Mayo endoscopic subscore (MES) remains inconclusive.

The electronic medical records of 177 adult UC patients evaluated at Mayo Clinic Rochester from January 2017 to March 2023 were retrospectively reviewed, obtaining clinical data and US-based Werfen Diagnostics FC levels collected within 30 days before colonoscopy or flexible sigmoidoscopy. Three independent inflammatory bowel disease specialist endoscopists blindly reviewed the most severe endoscopic images for grading MES.

The median interval between FC collection and endoscopy was 2 days. Fecal calprotectin showed strong positive correlations with MES (Spearman's r = 0.709; P < .01) and other clinical parameters. Fecal calprotectin cutoff of 60 mcg/g effectively distinguished MES 0 from MES 1-3 (sensitivity, 0.78; specificity, 0.97; area under the receiver operating characteristic curve [AUC], 0.901) and predicted clinical remission (Total Mayo Score ≤2 and no subscore >1; sensitivity, 0.83; specificity, 0.98; AUC, 0.921). Fecal calprotectin cutoff of 110 mcg/g effectively differentiated MES 0-1 from MES 2-3 (sensitivity, 0.86; specificity, 0.87; AUC, 0.915), while a cutoff of 310 mcg/g distinguished MES 0-2 from MES 3 (sensitivity, 0.80; specificity, 0.76; AUC, 0.820).

This study supports the reliability and applicability of FC as a valuable marker of endoscopic inflammation, particularly in distinguishing MES 0 from MES 1-3 using the FC cutoff of 60 mcg/g. Sensitivity analysis demonstrated robust results.

This American Gastroenterological Association (AGA) living guideline is intended to support practitioners in the pharmacological management of moderate-to-severe ulcerative colitis (UC).

A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to prioritize clinical questions, identify patient-centered outcomes, conduct an evidence synthesis, and develop recommendations on the pharmacological management of moderate-to-severe UC.

The AGA guideline panel made 14 recommendations. In adult outpatients with moderate-to-severe UC, the AGA recommends the use of infliximab, golimumab, vedolizumab, tofacitinib, upadacitinib, ustekinumab, ozanimod, etrasimod, risankizumab, and guselkumab, and suggests the use of adalimumab, filgotinib, and mirikizumab over no treatment. In patients who are naïve to advanced therapies, the AGA suggests using a higher-efficacy medication (eg, infliximab, vedolizumab, ozanimod, etrasimod, upadacitinib, risankizumab, and guselkumab) or an intermediate-efficacy medication (eg, golimumab, ustekinumab, tofacitinib, filgotinib, and mirikizumab) rather than a lower-efficacy medication (eg, adalimumab). In patients who have previously been exposed to 1 or more advanced therapies, particularly tumor necrosis factor (TNF)-α antagonists, the AGA suggests using a higher-efficacy medication (eg, tofacitinib, upadacitinib, and ustekinumab) or an intermediate-efficacy medication (eg, filgotinib, mirikizumab, risankizumab, and guselkumab) rather than a lower-efficacy medication (eg, adalimumab, vedolizumab, ozanimod, and etrasimod). In adult outpatients with moderate-to-severe UC, the AGA suggests against using thiopurine monotherapy for induction of remission, but suggests using thiopurine monotherapy over no treatment for maintenance of (typically corticosteroid-induced) remission. The AGA suggests against using methotrexate monotherapy, for induction or maintenance of remission. In adult outpatients with moderate-to-severe UC, the AGA suggests the use of infliximab, adalimumab, and golimumab in combination with an immunomodulator over corresponding monotherapy. However, the AGA makes no recommendation in favor of, or against, the use of non-TNF antagonist biologics in combination with an immunomodulator over non-TNF biologic alone. In patients with UC who are in corticosteroid-free clinical remission for at least 6 months on combination therapy of TNF antagonists and an immunomodulator, the AGA suggests against withdrawal of TNF antagonists, but makes no recommendation in favor of, or against, withdrawing immunomodulators. In adult outpatients with moderate-to-severe UC, who have failed 5-aminosalicylates, and have escalated to therapy with immunomodulators or advanced therapies, the AGA suggests stopping 5-aminosalicylates. Finally, in adult outpatients with moderate-severe UC, the AGA suggests early use of advanced therapies and/or immunomodulator therapy, rather than gradual step-up after failure of 5-aminosalicylates. The panel also proposed key implementation considerations for optimal use of these medications and identified several knowledge gaps and areas for future research.

This guideline provides a comprehensive, patient-centered approach to the pharmacological management of patients with moderate-to-severe UC.

Patients with ulcerative colitis (UC) who are hospitalised for acute severe flares represent a high-risk orphan population.

To provide guidance for clinical trial design methodology in these patients.

We created a multi-centre consortium to design and conduct a clinical trial for a novel therapeutic intervention (hyperbaric oxygen therapy) in patients with UC hospitalised for moderate-severe flares. During planning, we identified and addressed specific gaps for inclusion/exclusion criteria; disease activity measures; pragmatic trial design considerations within care pathways for hospitalised patients; standardisation of care delivery; primary and secondary outcomes; and sample size and statistical analysis approaches.

The Truelove-Witt criteria should not be used in isolation. Endoscopy is critical for defining eligible populations. Patient-reported outcomes should include rectal bleeding and stool frequency, with secondary measurement of urgency and nocturnal bowel movements. Trial design needs to be tailored to care pathways, with early intervention focused on replacing and/or optimising responsiveness to steroids and later interventions focused on testing novel rescue agents or strategies. The PRECIS-2 framework offers a means of tailoring to local populations. We provide standardisation of baseline testing, venous thromboprophylaxis, steroid dosing, discharge criteria and post-discharge follow-up to avoid confounding by usual care variability. Statistical considerations are provided given the small clinical trial nature of this population.

We provide an outline for framework decisions made for the hyperbaric oxygen trial in patients hospitalised for UC flares. Future research should focus on the remaining gaps identified.