Immune imbalance plays a key role in the pathogenesis of ulcerative colitis (UC). The changes in CD4+ T cells and regulatory T cells (Tregs) in colonic T cells have an important relationship with UC. It is of great significance to elucidate the functional characteristics of CD4+ cells andTregs in UC patients. This study aimed to inquire into changes in functional markers of CD4+T cells and Tregs, including Helios, Bcl6, CTLA-4, CD226, TIGIT, PD-1 and ICOS. DSS-induced colitis was established in Balb/c mice and lymphocytes from spleen, mesenteric lymph nodes (MLNs), peripheral blood, and colon tissue were obtained. CD4+T cells and Tregs were analyzed by flow cytometry. We found that Helios+ and Bcl-6+ proportions were increased in colonic CD4+T cells of DSS-induced colitis mice. CD4+FoxP3+CXCR5-Tregs were significantly elevated in the colon of colitis mice, with CTLA-4+ percentages increased. Naïve subsets in colonic CD4+T and Tregs were significantly reduced, while effector T-cell subsets were increased in colitis mice. TIGIT+ and CD226+ percentages were significantly increased in both colonic CD4+T cells and Tregs of colitis mice. Both PD-1+ and ICOS+ percentages in colonic CD4+T cells and the ICOS+ percentage in colonic Tregs were significantly increased in colitis mice. In conclusion, functional molecules related to CD4+T cells and Tregs in colonic T cells are altered in UC, often adopting an activated phenotype. These changes may be associated with the pathogenesis of UC and could potentially serve as clinical therapeutic targets.

To help navigate the complex treatment landscape of ulcerative colitis (UC), we quantified the benefit-risk trade-offs that patients were willing to make when choosing treatment.

Patients completed an online discrete choice experiment. Eligible patients had a UC diagnosis for ≥6 months, were aged ≥18 years, and resided in France, Germany, Italy, Spain, or the UK. Patients chose between 2 hypothetical treatments set up to ensure trade-offs were made. Clinical trial data, literature review, and patient interviews identified treatment attributes. Relative attribute importance (RAI) scores and maximum acceptable risks were generated. A patient-centric benefit-risk assessment of 200 mg of filgotinib was conducted as an example to show how measured trade-offs can be used.

Overall, 631 patients participated; patients had a mean age of 42.2 years and were predominantly male (75.3%). Achieving and maintaining clinical remission was the most important factor for patients (RAI 32.4%); to achieve this, patients were willing to accept slightly higher risks of blood clots, serious infections, and malignancies compared with lower risk treatment profiles. Patients also valued the convenience of oral treatments, avoiding steroids, and the ability to attend school/work. The patient-centric benefit-risk assessment suggested patients are significantly more likely to prefer Janus kinase 1 preferential inhibitor filgotinib over placebo.

Achieving clinical remission was the highest treatment priority for patients. To attain this, patients were willing to accept some slightly higher risk treatment profiles. Patient choices in the benefit-risk assessment suggested patients were significantly more likely to prefer filgotinib over placebo.

Obefazimod is an oral small molecule that selectively enhances the expression of a single micro-RNA (miRNA), miR-124. Obefazimod has demonstrated safety and efficacy in patients with moderate-to-severely active ulcerative colitis (UC) in a phase 2b induction trial. This analysis presents the 2-year outcome data of the open-label maintenance (OLM) study.

Patients received placebo or obefazimod 25, 50, or 100 mg once-daily (od) during the induction trial and, irrespective of their clinical response, could enter the 96-week OLM study with obefazimod 50 mg od. Safety was monitored through monthly visits in the first year and quarterly visits in the second year. Efficacy was assessed at weeks 48 and 96 using nonresponder imputation (NRI) for missing data.

Of 222 eligible patients, 217 were enrolled and 164 (75.6%) completed week 96 of the OLM study. Clinical response was achieved at weeks 48 and 96 in 177 (81.6%) and 158 (72.8%) patients and clinical remission in 119 (54.8%) and 114 (52.5%) of patients. A total of 133 (61.3%) and 128 (59.0%) patients showed endoscopic improvement, and 72 (33.2%) and 78 (35.9%) endoscopic remission. In total, 148/217 patients (68.2%) reported at least 1 treatment-emergent adverse event (TEAE). The most frequent TEAEs were COVID-19 (14.3%), headache (11.5%), UC (7.8%), and nasopharyngitis (6.9%). No new safety risks emerged over 96 weeks.

The 96-week OLM study supports the long-term efficacy and favorable safety profile of obefazimod 50 mg od. A phase 3 program with obefazimod in patients with moderate-to-severe UC is ongoing.

A phase 2b, open-label, efficacy and safety study of ABX464 as maintenance therapy in patients with moderate-to-severe UC. NCT04023396.

In this editorial, we discuss the article by Singh et al published in World Journal of Nephrology, stating the need for timely adjustments in inflammatory bowel disease (IBD) patients' long-term management plans. IBD is chronic and lifelong, with recurrence and remission cycles, including ulcerative colitis and Crohn's disease. It's exact etiology is unknown but likely multifactorial. Related to gut flora and immune issues. Besides intestinal symptoms, IBD can also affect various extraintestinal manifestations such as those involving the skin, joints, eyes and urinary system. The anatomical proximity of urinary system waste disposal to that of the alimentary canal makes early detection and the differentiation of such symptoms very difficult. Various studies show that IBD and it's first-line drugs have nephrotoxicity, impacting the patients' life quality. Existing guidelines give very few references for kidney lesion monitoring. Singh et al's plan aims to improve treatment management for IBD patients with glomerular filtration rate decline, specifically those at risk. Most of IBD patients are young and they need lifelong therapy. So early therapy cessation, taking into account drug side effects, can be helpful. Artificial intelligence-driven diagnosis and treatment has a big potential for management improvements in IBD and other chronic diseases.

Background/Objectives: The burden of ulcerative colitis (UC) is increasing in Saudi Arabia (KSA), and patients with UC often suffer from delays in diagnosis and appropriate management. This study investigates the current UC patient journey in KSA from the healthcare professionals' (HCPs) perspective. It aims to evaluate treatment patterns, identify critical gaps, and provide insights to guide interventions that enhance the quality of life for UC patients in KSA. Methods: Quantitative interviews were conducted with 60 HCPs (45 gastroenterologists and 15 internal medicine specialists) from different regions in Saudi Arabia (KSA) using a Computer-Assisted Personal Interview (CAPI) system. The survey domains included clinical symptoms, diagnostic testing, endoscopic scoring, treatment goals, and medication sequencing. Results: Data were collected from 60 HCPs with an average of 17 ± 12.5 years of experience. Most patients with UC were referred by general practitioners (28%), internal medicine physicians (25%), followed by surgeons (16%). The first-ranked treatment goals were clinical remission (53.3%), endoscopic remission (35%), and improvement of quality of life (33.3%). For outpatient moderate-to-severe UC, the most common first-line treatments are oral systemic steroids (34%), 5-aminosalicylates (5-ASAs) (26%), and TNF-α inhibitors (21%). While second-line treatment rankings were TNF-α inhibitors (23%), followed by Interleukin 12/23 inhibitors (19%), and Janus kinase (JAK) inhibitors (14%). Sphingosine 1-phosphate (S1P) receptor modulators are not well-utilized due to a lack of availability (88%), unfamiliarity with the treatment (24%), and formulary exclusion (12%). Conclusions: In conclusion, most UC patients are referred by general practitioners. Treating gastroenterologists prioritize clinical remission as a treatment goal. Corticosteroids remain overutilized as reflected by treating physicians' responses. The underutilization of advanced therapies underscores the need for enhanced education and improved access to integrate emerging therapies effectively.

A treat-to-target strategy for inflammatory bowel disease (IBD) recommends iterative treatment adjustments to achieve clinical and endoscopic remission. In asymptomatic patients with ongoing endoscopic activity, the risk/benefit balance of this approach is unclear, particularly with prior exposure to advanced therapies.

Using the RAND/University of California Los Angeles Appropriateness Method, 9 IBD specialists rated appropriateness of changing therapy in 126 scenarios of asymptomatic patients with ulcerative colitis and Crohn's disease and active endoscopic disease. Disease extent and behavior, prior treatment, prior complications, and recent disease progression were considered, as were factors that might influence decision-making, including age and pregnancy. Ratings were collected through anonymous survey, discussed at an in-person meeting, and finalized in a second anonymous survey.

Panelists rated change in therapy as appropriate (i.e., expected benefit sufficiently outweighs potential harms from continuing therapy) in 96/126 scenarios, generally in patients with progressive, complicated, and/or extensive disease, while changing therapy was rated uncertain in 27 scenarios of mild and/or stable disease. Changing therapy was rated inappropriate in ulcerative colitis patients with mild and stable disease previously exposed to ≥3 therapies or with improved endoscopic activity, and in Crohn's disease patients with only scattered aphthous ulcers. The validated threshold for disagreement was not crossed for any scenario. Patient age older than 65 years and a plan for pregnancy in the next year might influence decision-making in some settings.

Appropriateness ratings can help guide clinical decision-making about changing therapy to achieve endoscopic remission in asymptomatic patients with IBD until data from ongoing randomized studies are available.

Dill (Anethum graveolens L.) is a typical Uyghur medicine. It is traditionally used to treat sticky and stagnant dampness, hiccups and food stagnation, intestinal obstruction, and anorectal diseases.

Our study is designed to investigate the potential of alcohol extract from the aerial part of dill in ameliorating ulcerative colitis induced by Dextran Sulfate Sodium Salt (DSS) in mice.

In this paper, the chemical composition of the aerial part of dill was speculated from the data obtained by LC-MS and determined by comparing with 10 standards through HPLC. The aerial part of fresh dill was dried, crushed, sieved, and then extracted with 70% ethanol to obtain DE. The lipopolysaccharide (LPS)-induced RAW264.7 cells were used to test the anti-inflammatory activity of DE in vitro. The impact of DE on UC was also studied in vivo. UC was induced by drinking 2.5% DSS to C57BL/6 mice for 6 days. The positive control group received 5-aminosalicylic acid (5-ASA) by gavage, and the low and high-dose treatment groups were respectively given 200 mg/kg and 400 mg/kg of DE by gavage daily for 7 days from the first day.

DE significantly reduces the disease activity index (DAI) and colon histopathological damage. DE can also alleviate oxidative stress and inflammation in UC mice by reducing IL-6, IL-1β, MDA, and MPO levels and increasing CAT and GSH levels in colonic tissues. DE can protect the integrity of the colonic mucosal barrier by reducing damage to goblet cells, increasing the levels of mucin MUC2, and regulating the expression of tight junction proteins such as ZO-1, Occludin, Claudin-1, and Claudin-2. In addition, DE improves the ratio of beneficial and harmful bacteria, thus further alleviating the imbalance of intestinal flora.

DE has anti-inflammatory activity in vitro and an ameliorative effect on DSS-induced UC in mice by alleviating oxidative stress and inflammation, protecting the integrity of the intestinal barrier, and regulating intestinal flora.

Background/Objectives: The management of inflammatory bowel disease (IBD) varies due to differences in healthcare systems, treatment costs, access to diagnostics, and diverse clinical practices between specialists. Despite the frequent advocacy of a treat-to-target (T2T) approach, there is insufficient clarity on how clinicians implement T2T in real-world settings. We aim to conduct a large, global survey among IBD experts to identify current practices in management. Methods: A prospective, cross-sectional study was conducted using a 16-item survey divided into two sections-for ulcerative colitis (UC) and Crohn's disease (CD)-and distributed to practicing IBD clinicians. Results: A total of 261 respondents from 88 countries participated in the survey, with the majority (253/261) being physicians and eight being IBD nurse specialists. Despite global guidance, only a quarter of the respondents routinely perform an endoscopy to assess the response after starting an advanced therapy (28.4% in UC vs. 23.5% in CD). Moreover, despite an increasing academic focus on intestinal ultrasound (IUS), 171 (66%) of respondents in UC and 132 (51%) in CD reported that they do not routinely undertake IUS to guide treatment decisions. Faecal calprotectin for monitoring treatment response was routinely used by 87% (90% in UC and 84% in CD) of the respondents. Forty-five percent reported use of therapeutic drug monitoring (TDM) both proactively and reactively and 35% reported only using TDM reactively. Conclusions: Our study shows considerable variation in IBD management across different countries and interpretation of the T2T approach. This highlights the need for standardised and pragmatic guidelines to help improve outcomes for patients with IBD globally.

Inflammatory bowel diseases (IBD) including Crohn's disease (CD) and ulcerative colitis (UC) are chronic, relapsing conditions characterized by dysregulated immune responses and persistent intestinal inflammation. This review aims to examine new potential therapeutic targets in IBD starting from the STRIDE-II statements. Key targets now include clinical remission, endoscopic remission, and biomarker normalization (such as C-reactive protein and fecal calprotectin). Moreover, histologic remission, transmural remission, and in the future molecular targets are emerging as important indicators of sustained disease control. The treatment goals for inflammatory bowel disease are varied: to relieve symptoms, prevent permanent intestinal damage, promote inflammation remission, and minimize complications. Consequently, the therapeutic targets have evolved to become broader and more ambitious. Integrating these advanced therapeutic targets has the potential to redefine IBD management by promoting deeper disease control and improved patient outcomes. Further research is essential to validate these strategies and optimize their clinical implementation.

The management of inflammatory bowel disease has seen significant advancements with the introduction of endoscopic examinations, allowing for diagnosis, assessment of inflammation severity, and monitoring of treatment response. The frequency of follow-up endoscopies is personalized based on the factors such as the disease course and treatment response. Endoscopic findings should be well described, and biopsies should be acquired in a thoughtful, protocolized manner. While endoscopy is essential, it has certain limitations. It can be invasive, cause discomfort and associated with possible complications.

Vedolizumab is an approved ulcerative colitis (UC) treatment. Multiple large randomized clinical trials have demonstrated the drug's efficacy and safety. However, real-world data from Middle Eastern countries are spare. The study aims to evaluate the clinical efficacy of vedolizumab (VDZ) therapy in advanced therapy experienced UC patients.

A retrospective electronic chart review of a cohort study of 153 moderately to severely active UC patients who failed or were intolerant to TNF antagonists and received vedolizumab from two large tertiary care centers was performed. Rates of clinical response and remission were retrospectively evaluated at 3,6, and 12 months post VDZ therapy using Patient Simple Clinical Colitis Activity Index (P-SCCAI); clinical response was defined as a decrease in P-SCCAI ≥3, and clinical remission was defined as a P-SCCAI score of ≤3 points. Logistic regression analysis was used to identify predictors of response to vedolizumab.

A total of 153 UC patients had sufficient data for analysis. Clinical remission rates were 61.9% for patients on vedolizumab every 8 weeks and 89.3% for those receiving every 4 (Q4) weeks dosing. A significant reduction in CRP and improvement of albumin post vedolizumab treatment were observed, and corticosteroids were stopped in most patients. In a multiple logistic regression analysis, several factors were found to influence the clinical effectiveness of VDZ in inducing remission. Female gender was associated with a higher likelihood of remission [OR =3.09, 95% CI = (1.05-9.13), P = 0.04]. Conversely, a greater number of biologics used prior to VDZ treatment was associated with a lower likelihood of remission [OR =0.418, 95% CI = (0.203-0.859), P = 0.017]. Patients with extensive disease (E3) had an increased likelihood of remission [OR =3.81, 95% CI = (1.32-10.97), P = 0.0129]. Additionally, a VDZ dosing frequency of Q4 weeks was associated with a significantly higher likelihood of remission [OR =6.08, 95% CI = (1.73-21.39), P = 0.0049]. No significant safety signals were reported.

In this current real-world study, vedolizumab effectively achieved clinical response and remission in most advanced therapy experienced UC patients treated for up to 12 months. Future studies with larger sample sizes and more robust study designs should be conducted to further validate the results of this study.

Ulcerative colitis (UC), a prevalent form of inflammatory bowel disease (IBD), presents a significant clinical challenge due to the lack of optimal therapeutic strategies. Emerging evidence suggests that fibroblast growth factor 20 (FGF20) may play a crucial role in mitigating UC symptoms, though the mechanistic underpinnings remain elusive. In this study, a mouse model of UC was established using dextran sodium sulfate (DSS) to investigate the potential role of FGF20. Our findings revealed a marked reduction in FGF20 expression in the serum and colonic tissues of DSS-treated mice. Furthermore, FGF20 knockout did not exacerbate colonic damage in these mice. Conversely, overexpression of FGF20 via adeno-associated virus (AAV) significantly alleviated UC-associated symptoms. This alleviation was evidenced by attenuated intestinal shortening, mitigated weight loss, increased colonic goblet cell density and crypt formation, reduced inflammation severity and inflammatory cell infiltration, and enhanced expression of tight junction and mucin proteins. Moreover, FGF20 significantly ameliorated the dysbiosis of gut microbiota in DSS-treated mice by increasing the abundance of beneficial bacteria and decreasing the abundance of harmful bacteria. The beneficial effects of FGF20 were notably attenuated following gut microbiota depletion with an antibiotic regimen. Fecal microbiota transplantation experiments further supported the critical role of gut microbiota in mediating the effects of FGF20 on DSS-treated mice. In conclusion, these findings highlight the potential involvement of gut microbiota in the therapeutic effects of FGF20 in UC.

Mirikizumab, a p19-directed interleukin-23 monoclonal antibody, is efficacious in inducing clinical remission at week 12 (W12) and maintaining clinical remission at W52 in patients with moderately to severely active ulcerative colitis. Results are presented from the open-label extension study through W104.

Clinical, symptomatic, quality-of-life, and adverse event outcomes are reported for mirikizumab induction responders and extended induction responders, including biologic-failed patients, who entered LUCENT-3, with data shown for W52 maintenance responders or remitters. Discontinuations or missing data were handled by nonresponder imputation (NRI), modified NRI (mNRI), and observed case (OC).

Among W52 mirikizumab responders, clinical response at W104 was 74.5%, 87.2%, and 96.7% and clinical remission was 54.0%, 62.8%, and 70.1% for NRI, mNRI, and OC, respectively. Among W52 mirikizumab remitters, clinical response at W104 was 76.6%, 89.0%, and 98.3% and clinical remission was 65.6%, 76.1%, and 84.2%. Using mNRI, remission rates at W104 for W52 clinical remitters were 74.7% corticosteroid-free, 79.5% endoscopic, 63.9% histologic-endoscopic mucosal remission, 85.9% symptomatic, 59.8% bowel urgency, 80.5% Inflammatory Bowel Disease Questionnaire (using NRI), 71.2% histologic-endoscopic mucosal improvement, and 77.5% bowel urgency improvement. Previous biologic-failed vs not-biologic-failed patient data were generally similar. Extended induction mNRI clinical response was 81.9%. Serious adverse events were reported in 5.2% of patients; 2.8% discontinued treatment due to adverse events.

Endoscopic, histologic, symptomatic, and quality-of-life outcomes support the long-term benefit of mirikizumab treatment up to 104 weeks in patients with ulcerative colitis, including biologic-failed patients, with no new safety concerns.

The benefits of deep disease healing need evaluation by long-term clinical research in different populations. Confocal laser endomicroscopy (CLE) is a superior method for evaluating deep disease healing.

This prospective study enrolled ulcerative colitis (UC) patients in clinical remission who underwent colonoscopy, CLE, and histological assessment. Patients were monitored for relapse by patient-reported outcomes and colonoscopy evaluation of mucosal healing. The ability of different methods of mucosal healing to predict long-term disease recurrence was assessed using Kaplan-Meier estimation and Cox proportional hazard regression.

Forty-two patients in clinical remission were assessed by colonoscopy. Those with Mayo endoscopic subscores (MES) ≤ 1 were enrolled. The 48-month recurrence rates in present healing group, assessed by CLE (colonic barrier assessment and ENHANCE index) and by histological examination (Geboes scale), were 20.0%, 26.7%, and 11.1%, respectively, and were significantly lower than absent healing group (P < 0.05). Univariate Cox proportional risk regression analysis in absent of healing disease, determined by the ENHANCE index and Geboes scale, indicated an increased risk of recurrent events, with hazard ratios (HR) of 3.87 (95% CI: 1.18, 12.62) and 8.20 (95% CI: 1.06, 63.30), respectively. Multivariate Cox proportional hazard regression analysis adjusted for the extent of inflammation (E3 or not) showed a significant difference only for the ENHANCE index, with an HR of 3.53 (95% CI: 1.03, 12.10), P = 0.045.

Deep disease healing has a lower recurrence rate. The colonic barrier healing assessment, ENHANCE index, and histological Geboes scale have superior long-term prognostic value for UC patients.

Mirikizumab, a p19-directed interleukin-23 monoclonal antibody, has demonstrated induction of clinical remission at week 12 with maintenance through week 104 in patients with moderately-to-severely active ulcerative colitis (UC). Results are presented from the LUCENT-3 open-label extension study through week 152.

Of 868 LUCENT clinical trial program mirikizumab-treated induction patients, 544 were responders of whom 365 were rerandomized to mirikizumab maintenance. Of these, 324 completed week 52 and 316 entered extension treatment (286 week 52 responders; 179 week 52 remitters). Efficacy and safety outcomes are reported for mirikizumab-treated LUCENT-3 participants, including biologic-failed patients, with data for week 52 maintenance responders/remitters. Discontinuations or missing data were handled by nonresponder imputation, modified nonresponder imputation (mNRI), and observed cases.

Using mNRI, 81.6% of week 52 responders demonstrated clinical response at week 152. Week 152 remission rates for week 52 responders included clinical (56.1%), corticosteroid-free (CSF; 54.5%), endoscopic (61.0%), histologic-endoscopic mucosal remission (HEMR; 52.6%), symptomatic (74.9%), and bowel urgency (BU; 58.6%). At week 152, 53.3% of week 52 responders achieved histologic-endoscopic mucosal improvement (HEMI) and 74.3% achieved BU clinically meaningful improvement (CMI). Among week 52 remitters, 85.4% showed a clinical response at week 152, with clinical (70.1%), CSF (68.9%), endoscopic (72.0%), HEMR (63.4%), symptomatic (81.4%), and BU (60.8%) remission. At week 152, among week 52 remitters, 64.0% of patients achieved HEMI and 75.6% achieved BU CMI. Stool frequency, rectal bleeding, BU, and abdominal pain score reductions from induction baseline to maintenance week 52 were sustained through week 152 for week 52 completers. Overall, in the safety population, 7.4% of patients reported severe adverse events (AEs); 5.3% discontinued treatment due to AEs. AEs of special interest included opportunistic infection (1.8%), hepatic disorders (3.2%), cerebrocardiovascular events (1.5%), and malignancy (0.3%). Patients with antidrug antibodies reduced over time from 23.6% in year 1 to 3.2% in year 3.

Symptomatic, clinical, endoscopic, histologic, and quality-of-life outcomes support long-term sustained benefit of mirikizumab treatment up to 152 weeks in patients with UC, including biologic-failed patients, with no new safety concerns.

ClinicalTrials.gov: NCT03518086; NCT03524092; NCT03519945.

As a chronic autoinflammatory condition, ulcerative colitis is often managed via systemic immunosuppressants. Here we show, in three mouse models of established ulcerative colitis, that a subcutaneously injected colon-specific immunosuppressive niche consisting of colon epithelial cells, decellularized colon extracellular matrix and nanofibres functionalized with programmed death-ligand 1, CD86, a peptide mimic of transforming growth factor-beta 1, and the immunosuppressive small-molecule leflunomide, induced intestinal immunotolerance and reduced inflammation in the animals' lower gastrointestinal tract. The bioengineered colon-specific niche triggered autoreactive T cell anergy and polarized pro-inflammatory macrophages via multiple immunosuppressive pathways, and prevented the infiltration of immune cells into the colon's lamina propria, promoting the recovery of epithelial damage. The bioengineered niche also prevented colitis-associated colorectal cancer and eliminated immune-related colitis triggered by kinase inhibitors and immune checkpoint blockade.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis (UC), remains a clinically complex condition in children and adults. This study is a systematic analysis of key developments in the treatment of inflammatory bowel diseases, as well as their efficacy and safety over time. Early diagnosis of pediatric IBD is very important since it affects growth and development in children. New therapeutic approaches like biological agents, small molecules, and gene or targeted drugs have given the medical fraternity new treatment protocols. There is a trend towards more selective therapies for adult IBD, especially for anti-tumor necrosis factor (anti-TNF) biologics, integrin antagonists, and interleukin-12/23 (IL-12/23) inhibitors. This review emphasizes the need for patient management where early intervention leading to mucosal healing has been identified to predict durable outcomes. Systematic analysis of existing literature comparing childhood and adult populations shows that morbidity, pathophysiology, therapeutic outcome, as well as the potential for adverse outcomes are dissimilar, which supports the need for differentiated therapy. This work also looks at long-term consequences of the intervention course, the avoidance of surgery, and an improvement in the quality and stability of life as well as reduction in further development of malignant transformation. The new developing strategy of gut microbiome modification and nutrition support for maintaining remission is also argued. Despite these progresses, issues still persist concerning the effectiveness of treatments, side effects, and patients' compliance. These recommendations give this review a prospective outlook of treatment regimens likely to define the future of IBD management for all age groups.

As a direct result of the COVID-19 pandemic, many advances in telehealth have been made that save time and reduce travel costs for patients. Telehealth, specifically video visits, was especially embraced by patients with inflammatory bowel disease (IBD). However, remote clinic visits are only one part of the equation for remote IBD care. Patients with Crohn's disease or ulcerative colitis have a significant testing burden, and many strides still need to be made to improve all aspects of their care, including remote monitoring (testing at home) of biochemical markers (eg, C-reactive protein and fecal calprotectin) and drug concentrations. Remote monitoring has the potential to decrease the burden of chronic disease on patients through improved ease of access, both when patients are feeling well and when they are having an exacerbation of symptoms. Numerous technologies are available in other countries, are used in other disease states, or are in the animal or early human testing phases. These innovations in home testing have the potential to improve testing adherence, disease control, and monitoring of IBD for all patients, and will have a particularly significant effect on those living in rural communities. This article reviews the current modalities for remote monitoring of patients with IBD as well as the methods in development to make monitoring of IBD easier for patients.

Assessment and scoring of histological images in Ulcerative colitis (UC) is prone to inter- and intra-observer variability. This study aimed to investigate whether an artificial intelligence (AI) system developed using image processing and machine learning algorithms could measure histological disease activity based on the Nancy index.

A total of 200 histological images of patients with UC were used in this study. A novel AI algorithm was developed using state-of-the-art image processing and machine learning algorithms based on deep learning and feature extraction. The cell regions of each image, followed by the Nancy index, were manually annotated and measured independently by four histopathologists. Manual and AI-automated measurements of the Nancy index score were conducted and assessed using the intraclass correlation coefficient (ICC).

The 200-image dataset was divided into two groups (80% was used for training and 20% for testing). Intraclass correlation coefficient statistical analyses were performed to evaluate the AI tool and used as a reference to calculate the accuracy. The average ICC among the histopathologists was 89.3 and the average ICC between histopathologists and the AI tool was 87.2. The AI tool was found to be highly correlated with histopathologists.

The high correlation of performance of the AI method suggests promising potential for inflammatory bowel disease clinical applications. A standardized automated histological AI-driven scoring system can potentially be used in daily inflammatory bowel disease practice to reduce training needs and resource use, eliminate the subjectivity of the pathologists, and assess disease severity for treatment decisions.

Ulcerative colitis (UC) is a chronic inflammatory bowel disorder (IBD) with periods of relapse and remission. Current advancements in clinical research have led to the development of more refined and effective medical therapy for UC.

Traditional therapeutic agents such as 5-aminosalicylates (5-ASAs), sulfasalazine (SASP), corticosteroids, and immunomodulatory drugs have remained the gold standard for decades. However, their novel formulations and dosage regimens have changed their sequences in the medical management of UC. Several other novel drugs are in the final phases of clinical development or have recently received regulatory approval designed to target specific mechanisms involved in the inflammatory cascade for UC.

This narrative review sought to provide a comprehensive knowledge of the potential benefits of standard and emerging therapies, including novel formulations, new chemical entities, and novel therapeutic approaches in managing UC. Keywords: Ulcerative colitis, 5- Aminosalicylic acid, sulfasalazine, corticosteroids, biologics, immunomodulators, novel formulations.

Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is characterized by chronic gastrointestinal inflammation. A high unmet need exists for noninvasive biomarkers in IBD to monitor changes in disease activity and guide treatment decisions. Stool is an easily accessed, disease proximal matrix in IBD, however the composition of the IBD fecal proteome remains poorly characterized.

A data-independent acquisition LC-MS/MS approach was used to profile the human fecal proteome in two independent cohorts (Cohort 1: healthy n = 5, UC n = 5, CD n = 5, Cohort 2: healthy n = 20, UC n = 10, and CD n = 10) to identify noninvasive biomarkers reflective of disease activity.

688 human proteins were quantified, with 523 measured in both cohorts. In UC stool 96 proteins were differentially abundant and in CD stool 126 proteins were differentially abundant compared to healthy stool (absolute log2 fold change > 1, p-value < 0.05). Many of these fecal proteins are associated with infiltrating immune cells and ulceration/rectal bleeding, which are hallmarks of IBD pathobiology. Mapping the identified fecal proteins to a whole blood single-cell RNA sequencing data set revealed the involvement of various immune cell subsets to the IBD fecal proteome.

Findings from this study not only confirmed the presence of established fecal biomarkers for IBD, such as calprotectin and lactoferrin, but also revealed new fecal proteins from multiple pathways known to be dysregulated in IBD. These novel proteins could serve as potential noninvasive biomarkers to monitor specific aspects of IBD disease activity which could expedite clinical development of novel therapeutic targets.

Ulcerative colitis (UC), characterized by its recurrent nature, imposes a significant disease burden and compromises the quality of life. Emerging evidence suggests that achieving clinical remission is not sufficient for long-term remission. In pursuit of a favorable prognosis, mucosal healing (MH) has been defined as the target of therapies in UC. This paradigm shift has given rise to the formulation of diverse endoscopic and histological scoring systems, providing distinct definitions for MH. Endoscopic remission (ER) has been widely employed in clinical practice, but it is susceptible to subjective factors related to endoscopists. And there's growing evidence that histological remission (HR) might be associated with a lower risk of disease flares, but the incorporation of HR as a routine therapeutic endpoint remains a debate. The integration of advanced technology has further enriched the definition of deep MH. Up to now, a universal standardized definition for deep MH in clinical practice is currently lacking. This review will focus on the definition of deep MH, from different dimensions, and analyze strengths and limitations, respectively. Subsequent multiple large-scale trials are needed to validate the concept of deep MH, offering valuable insights into potential benefits for UC patients.

A prior study in this journal, "Clinicians Are from Mars and Pathologists Are From Venus," demonstrated that clinicians can erroneously interpret pathology reports up to 30% of the time. After noticing reporting heterogeneity in the setting of inflammatory bowel disease (IBD), we speculated that a standardized synoptic report could improve gastroenterologist comprehension.

To investigate the effect of a synoptic table on gastroenterologist comprehension of IBD pathology reports.

We recruited gastroenterology fellows and faculty to participate in this study. All participants were given 6 pathology reports and asked if the following were present: active inflammation, chronic inflammation, IBD, and dysplasia. Participants were also asked to rate their confidence. After a 6-week washout period, the same questionnaire was distributed with a synoptic report. We performed paired t-tests to compare the mean accuracy and confidence scores between the preintervention and postintervention responses.

A total of 39 physicians participated: 9 fellows and 30 faculty. Mean accuracy scores were higher after the intervention (0.81 versus 0.86; P < .001). Mean confidence was also higher after intervention, but this was not statistically significant (3.91 versus 3.98; P = .24).

The improvement in accuracy scores after intervention confirms that clinician comprehension improved with the synoptic table. A synoptic report may provide a standardized way of communicating diagnostic information to clinicians in the setting of IBD and potentially other inflammatory conditions.

To investigate the therapeutic efficiency of a novel drink termed "Ferment" in cases of ulcerative colitis (UC) and its influence on the gut microbiota.

In this study, we developed a complex of mixed fruit juice and lactic acid bacteria referred to as Ferment. Ferment was fed to mice for 35 days, before inducing UC with Dextran Sulfate Sodium Salt. We subsequently investigated the gut microbiome composition using 16S rRNA sequencing.

After Ferment treatment, mouse body weight increased, and animals displayed less diarrhea, reduced frequency of bloody stools, and reduced inflammation in the colon. Beneficial bacteria belonging to Ileibacterium, Akkermansia, and Prevotellacea were enriched in the gut after Ferment treatment, while detrimental organisms including Erysipelatoclostridium, Dubosiella, and Alistipes were reduced.

These data place Ferment as a promising dietary candidate for enhancing immunity and protecting against UC.

Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis [UC]. This post-hoc analysis of the phase 2 OASIS trial [NCT02447302] evaluated its efficacy for endoscopic improvement-histologic remission [EIHR] and assessed correlation between faecal calprotectin [FCP] and C-reactive protein [CRP] levels with efficacy outcomes.

In total, 156 adults with moderately to severely active UC received once-daily etrasimod (1 mg [n = 52]; 2 mg [n = 50]) or placebo [n = 54] for 12 weeks. Clinical, endoscopic, and histologic variables were evaluated at baseline and Week 12. EIHR was defined as achievement of endoscopic improvement [endoscopic subscore ≤ 1, without friability] and histologic remission [Geboes score < 2.0]. Outcomes included the relationships between FCP and CRP concentration and clinical, endoscopic, and histologic variables.

Achievement of EIHR was significantly higher in patients who received etrasimod 2 mg versus placebo [19.5% vs 4.1%; Mantel-Haenszel estimated difference, 15.4%; p = 0.010]. In the etrasimod 2 mg group, median FCP and CRP levels at Week 12 were significantly lower in patients who achieved clinical remission, endoscopic improvement, histologic remission, and EIHR versus patients who did not [all p < 0.05]. An FCP concentration cutoff of 250 µg/g achieved optimum sensitivity and specificity for efficacy, including EIHR [0.857 and 0.786, respectively; κ coefficient, 0.3584]. Higher proportions of patients with FCP ≤ 250 µg/g achieved efficacy outcomes at Week 12 versus patients with FCP > 250 µg/g.

Etrasimod was effective for inducing EIHR in patients with UC. FCP and CRP may be useful, noninvasive biomarkers to monitor treatment response.

NCT02447302.

Crohn's disease (CD) is a chronic and debilitating inflammatory bowel disease that affects millions of individuals worldwide. Despite the availability of various treatment options, a significant number of patients do not achieve remission or experience adverse effects with conventional therapies. Vedolizumab, a novel therapeutic agent, has emerged as a promising approach in the management of CD. Despite improvements in treatment choices, there is still a demand for medicines that are efficient and well-tolerated. Vedolizumab, a monoclonal antibody targeting α4β7 integrin, has emerged as a promising therapeutic approach for the treatment of CD. The review aims to provide a summary of vedolizumab, current treatment options, impact of vedolizumab on the patient's quality of life, mechanism of action, clinical effectiveness, safety and efficacy of vedolizumab, potential side effects or risks associated with vedolizumab therapy, and potential predictors. Furthermore, we investigate limitations and challenges associated with vedolizumab and possible future developments and medical implications. This review provides a comprehensive examination of the present data supporting vedolizumab as a possible treatment option for CD, highlighting its benefits and outlining prospective directions for future study and clinical practice improvement.

Ulcerative colitis (UC) is a chronic problem of the intestine and relapsing in nature. Biochanin A is a nature-derived isoflavonoid and has numerous bioactivities. However, its role against UC and intestinal inflammation remains obscure. We aimed to comprehensively explore the pharmacological effect of biochanin A in alleviating colitis and to evaluate the potential mechanisms. Initially, we explored the anti-inflammatory action of biochanin A (15, 30, and 60 μM) by employing lipopolysaccharide (LPS)-activated RAW 264.7 cells. In RAW 264.7 cells under LPS stimulation, biochanin A inhibited the elevation of reactive oxygen species (ROS) (p < 0.0001), interleukin (IL)-1β (p < 0.0001), IL-18 (p < 0.01), and tumor necrosis factor (TNF)-α (p < 0.01) release, nitrite production (p < 0.0001), and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins. Next, we studied the effectiveness of biochanin A (20 and 40 mg/kg) in mouse colitis induced with dextran sulfate sodium (DSS) by assessing colon length, disease activity index (DAI) scoring, and performing colonoscopy and histological analysis. The pro-inflammatory cytokines were estimated using ELISA. Western blot studies were performed to assess underlying mechanisms. In mice, biochanin A treatment alleviated DAI score (p < 0.0001), restored colon length (p < 0.05) and morphology, and re-established colon histopathology. Biochanin A affects the phosphorylation of proteins associated with NF-κB (p65) and mitogen-activated protein kinase (MAPK) axis and regulates colonic inflammation by reducing the expression of inflammatory cytokines and myeloperoxidase (MPO) activity. Altogether, our findings support the idea that the anticolitis potential of biochanin A is allied with anti-inflammatory activity by inhibiting the MAPK/NF-κB (p65) axis. Hence, biochanin A may be an alternative option to alleviate the risk of colitis.

Ulcerative colitis is a chronic, spontaneous inflammatory bowel disease that primarily affects the colon. This study aimed to explore how Porphyra haitanensis porphyran (PHP) modulates the immune response and the associated mechanisms that alleviate dextran sulphate sodium-induced colitis in mice. Histological assessments via H&E staining and AB-PAS staining revealed that PHP intervention partially restored the number of goblet cells and improved intestinal mucosal function. Immunohistochemical and Western blot analyses of claudin-1, occludin, and MUC-2 demonstrated that PHP could repair the intestinal barrier and reduce colon damage by upregulating the expression of these proteins. PHP intervention was associated with a decrease in pro-inflammatory cytokine expression and an increase in anti-inflammatory cytokine expression. Moreover, the expression of proteins involved in intestinal immune homing, such as CCR-9, CCL-25, MAdCAM-1, and α4β7, was significantly suppressed in response to PHP treatment. Conversely, PHP upregulates the expression of CD40 and TGF-β1, both of these can promote healing and reduce inflammation in the gut lining. This study demonstrates that PHP can ameliorate ulcerative colitis by enhancing the intestinal barrier and modulating immune responses. These findings offer valuable insights into the potential utility of P. haitanensis as a promising natural product for managing ulcerative colitis.

Artificial intelligence (AI) is quickly demonstrating the ability to address problems and challenges in the care of IBD. This review with commentary will highlight today's advancements in AI applications for IBD in image analysis, understanding text, and replicating clinical knowledge and experience.

Advancements in machine learning methods, availability of high-performance computing, and increasing digitization of medical data are providing opportunities for AI to assist in IBD care. Multiple groups have demonstrated the ability of AI to replicate expert endoscopic scoring in IBD, with expansion into automated capsule endoscopy, enterography, and histologic interpretations. Further, AI image analysis is being used to develop new endoscopic scoring with more granularity and detail than is possible using conventional methods. Advancements in natural language processing are proving to reduce laborious tasks required in the care of IBD, including documentation, information searches, and chart review. Finally, large language models and chatbots that can understand language and generate human-like replies are beginning to exhibit clinical intelligence that will revolutionize how we deliver IBD care. Today, AI is being deployed to replicate expert judgement in specific tasks where disagreement, subjectivity, and bias are common. However, the near future will herald contributions of AI doing what we cannot, including new detailed measures of IBD, enhanced analysis of images, and perhaps even fully automating care. As we speculate on future technologic capabilities that may improve how we care for IBD, this review will also consider how we will implement and fairly use AI in practice.

Predicting the efficacy of molecular-targeted drugs (MTDs) is an unmet need in the treatment of ulcerative colitis (UC). Intestinal ultrasound (IUS) can be used to safely and repeatedly assess UC activity.

Thirty-eight patients who started MTD therapy for active UC and underwent IUS at baseline and 3 months after starting therapy were analyzed. Steroid-free clinical remission (SFCR) and endoscopic improvement (EI) at 6 months were defined as a Lichtiger index of ≤3 and Mayo endoscopic subscore of ≤1 while continuing the MTD without steroid induction or surgery. Sonographically estimated EI (SE-EI) at 3 months was assessed based on a Milan Ultrasound Criterion of ≤6.2 and Kyorin Ultrasound Criterion for UC (bowel wall thickness of <3.8 mm and submucosa index of <50%).

Thirty-one patients achieved SFCR at 6 months [SFCR(+) group]. The SFCR(+) group demonstrated significantly better improvement in bowel wall thickness and bowel wall vascularity at 3 months than the SFCR(-) group. The Milan Ultrasound Criterion and UC-IUS index also improved significantly more in the SFCR(+) than SFCR(-) group. The areas under the curve of these parameters for predicting SFCR were approximately 0.80. Colonoscopy was performed for 28 patients at 6 months, and 15 patients achieved EI. SE-EI at 3 months was significantly associated with achievement of EI at 6 months. The positive predictive values of SE-EI at 3 months for SFCR and EI at 6 months were 100%.

Sonographic improvements in 3 months predicted the clinical and endoscopic efficacy of MTD therapy at 6 months, suggesting the longitudinal significance of IUS monitoring for UC treatment.

Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) that contributes in part to irreversible bowel damage and long-term complications, reduced quality of life, invalidity, and economic burden. Suboptimal control of IBD is associated with higher healthcare resource utilization (HCRU), impaired quality of life (QoL), and reduced work productivity.

The IBD-PODCAST study aimed to assess the proportion of IBD patients with suboptimal control and its associated impact.

IBD-PODCAST is a cross-sectional, multicenter study that aimed to characterize the CD and UC population with optimal or suboptimal control according to the STRIDE-II criteria and patient- and physician-reported measures. Here we present the results of the Spanish cohort (n = 396).

A total of 104/196 (53.1%) CD and 83/200 (41.5%) UC patients were found to have suboptimal disease control. Long-term treatment targets according to STRIDE-II were applied in 172 (87.8%) CD and 181 (90.5%) UC patients. 125 of 172 (72.7%) CD and 74 of 181 (40.9%) UC patients were currently treated with targeted immunomodulators. Patients with CD and UC and suboptimal disease control showed impaired QoL, higher HCRU and direct costs, and also loss of work productivity compared to those with optimal control.

Despite a high rate of targeted immunomodulator therapy, a substantial proportion of IBD patients show suboptimal disease control according to the STRIDE II criteria. Those patients with suboptimal disease control exhibit impaired QoL, less work productivity, and higher HCRU, suggesting that there is considerable need for better treatment approaches in IBD.

Endoscopic activity is associated with an increased risk of surgery in patients with ulcerative colitis [UC]. Transmural activity, as defined by Milan Ultrasound Criteria [MUC] > 6.2, reliably detects endoscopic activity in patients with UC. The present study aimed to assess in UC patients whether transmural severity is a better predictor of colectomy as compared to endoscopy.

Consecutive adult UC patients were recruited in two IBD Referral Centres and underwent colonoscopy and intestinal ultrasound in a blinded fashion. The need for colectomy was assessed at follow-up. Univariable and multivariable logistic and Cox regression analyses were performed. Receiver operating characteristic [ROC] analysis was used to compare MUC baseline values and Mayo Endoscopic Scores [MES] in predicting colectomy risk.

Overall, 141 patients were enrolled, and 13 underwent colectomy in the follow-up period. Both MES (hazard ratio [HR]: 3.15, 95% confidence interval [CI]: 1.18-8.37, p = 0.02) and MUC [HR: 1.48, 95% CI: 1.19-1.76, p < 0.001] were associated with colectomy risk, but only MUC was independently associated with this event on multivariable analysis [HR: 1.46, 95% CI: 1.06-2.02, p = 0.02]. MUC was the only independent variable associated with colectomy risk in patients with clinically active disease (odds ratio [OR]: 1.53 [1.03-2.27], p = 0.03). MUC demonstrated higher accuracy than MES (area under ROC curve [AUROC] 0.83, 95% CI: 0.75-0.92 vs 0.71, 95% CI: 0.62-0.80) and better performance for predicting colectomy [p = 0.02]. The optimal MUC score cut-off value for predicting colectomy, as assessed by the Youden index, was 7.7.

A superior predictive value was found for transmural vs endoscopic severity for colectomy risk in UC patients.

Inflammatory bowel disease (IBD) treatment was revolutionised with the arrival of biological therapy two decades ago. There are now multiple biologics and increasingly novel small molecules licensed for the treatment of IBD. Treatment guidelines highlight the need for effective control of inflammation and early escalation to advanced therapies to avoid long-term complications. Consequently, a large proportion of patients with IBD receive advanced therapies for a long time. Despite their beneficial risk-benefit profile, these treatments are not without risk of side effects, are costly to healthcare providers and pose a burden to the patient. It is, therefore, paramount to examine in which circumstances a temporary cessation of therapy can be attempted without undue clinical risk. Some patients may benefit from cyclical rather than continuous treatment. This review examines the risk of relapse after discontinuation of advanced therapies, how to identify patients at the lowest risk of relapse and the chance of recapturing response when flaring after discontinuation.

Immune disorders arise from complex genetic and environmental factors, which lead to dysregulation at the cellular and inflammatory levels and cause tissue damage. Recent research highlights the crucial role of reactive antibodies in autoimmune diseases and graft rejection, but their complex determination poses challenges for clinical use. Therefore, our study aimed to ascertain whether the presence of reactive antibodies against membrane antigens in tissues from both animal models and humans could serve as biomarkers in patients with autoimmune disorders. To address this issue, we examined the binding profile of serological antibodies against a diverse panel of cell membranes from the spleen, liver, and kidney tissues of monkeys, rats, and humans. After developing the cell membrane microarrays, human sera were immunologically assayed. The study was first conducted on sera from two groups, healthy subjects and patients with inflammatory and autoimmune disorders, and then optimized for kidney transplant patient sera. A significant increase in antibody reactivity against specific monkey kidney and spleen membranes was observed in the serum of patients with lupus nephritis, while kidney transplant patients showed a significant enhancement against human tissues and human embryonic kidney 293 cells. These results show the potential importance for clinical and basic research purposes of studying the presence of specific IgG against membrane antigens in patients' serum as potential biomarkers of immune disorders. However, it is important to note that these results need to be verified in further studies with a larger sample size to confirm their relevance.

The landscape of ulcerative colitis has changed in the last two decades. Advancements in pharmacotherapeutics have heralded the introduction of new treatment options, with many agents in development. Better clinical outcomes are seen with tighter disease control, made possible with greater understanding of inflammatory pathways and their blockade with drugs. There has been a resultant shift in treatment targets, beyond symptoms to endoscopic and histological healing. Controlling the burden of disease activity also lowers the risk of developing colorectal cancer. Colorectal cancer screening now requires the use of dye-based agents and high-definition colonoscopy to improve the detection of colonic neoplasms.

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by chronic inflammation of the gastrointestinal tract, affecting millions of individuals throughout the world, and producing an impaired health-related quality of life. Granulocyte and monocyte apheresis (GMA) is a therapeutic option for UC management to induce remission by selective removal of activated leukocytes from bloodstream. Despite the knowledge of the important role of epigenetics in UC pathogenesis, and in the response to different treatments, nothing is known about the role of microRNAs in GMA therapy in UC patients.

Seven consecutively UC patients who started GMA in combo therapy with infliximab were recruited. Peripheral blood samples were taken before the apheresis session, at the start of the induction (S0) and at the end (S10). They were follow-up during the induction phase (10 sessions: 2 sessions for a week during 3 wk and 1 session for a week during 4 wk) of the treatment at a tertiary hospital (Hospital la Fe) and 6 mo after finishing the GMA induction therapy. MiRNA was extracted and analyzed by RT-PCR. R software and GraphPad were used.

Clinical disease activity significantly decreased after induction therapy with GMA (median partial Mayo score 2 (IQR, 1-6) (P < .05). Fecal calprotectin value and CRP value significantly decreased after induction therapy. Five microRNAs modified their expression during GMA (unsupervised analysis): miR-342-3p, miR-215-5p, miR-376c-3p, miR-139-5p, and miR-150-5p. When a sub-analysis was performed in those patients who showed good response to apheresis treatment (n = 5), two microRNAs showed to be implicated: miR-215-5p and miR-365a-3p. These are preliminary but promising and novel results, as it is the first time, to our knowledge that microRNA profiles have been studied in the context of GMA treatment for IBD.