Ulcerative Colitis Patients Research Articles

Association of oral manifestations with severity of the disease in ulcerative colitis patients

ObjectiveInflammatory bowel diseases (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC), are chronic conditions primarily affecting the intestines. This study aims to identify the nature and frequency of oral symptoms and signs in patients with ulcerative colitis and to explore the connection between these complications and the activity of the disease.MethodsThis descriptive-analytical study involved ulcerative colitis patients who visited the gastroenterology clinic at Shahid Sayad Shirazi Hospital in Gorgan, along with an equal number of healthy companions as a control group in 2019. A gastroenterology internist assessed the disease severity through clinical examination and a simple clinical disease activity index for colitis patients. The collected data were then analyzed statistically using SPSS version 19.ResultsThe average age of patients in the case group was 41.84 ± 11.66 years, while in the control group it was 40.43 ± 12.67 years. There was a significant correlation between difficulty swallowing, burning sensation in the mouth, vomiting, acidic taste, the presence of oral ulcers, and a coated tongue with the severity of disease activity (p < 0.05). However, no significant relationship was found between other variables and the severity of disease activity (p > 0.05).ConclusionThe results of this study confirm that as the severity of ulcerative colitis increases, the occurrence of oral lesions also rises, particularly during severe disease activity. Among oral symptoms, dry mouth had the highest incidence, followed by bad breath and changes in taste. The most common oral lesions observed were a coated tongue, grooved tongue, and oral ulcers, respectively.

Calibration, Clinical Utility and Specificity of Clinical Decision Support Tools in Inflammatory Bowel Disease

Background and AimsClinical decision support tools (CDSTs) have been developed to predict response to vedolizumab (VDZ) and ustekinumab (UST) in Crohn’s disease (CD) and ulcerative colitis (UC). In addition to assessing their discrimination performance, our study aimed to evaluate their calibration, clinical utility and specificity. MethodsWe included 280 CD and 218 UC patients initiating VDZ, and 194 CD patients initiating UST. We assessed discrimination by comparing rates of effectiveness outcomes between response probability groups forecasted by CDSTs. Calibration curves and decision curve analysis evaluated the calibration and clinical utility of VDZ-CDSTs. Additionally, we examined the agreement between UST-CDST and VDZ-CDST in assigning response probability groups among CD patients starting UST. ResultsIn the overall cohort, CDSTs allocated 7.2%, 50.0% and 42.8% of the patients to the low, intermediate and high response probability groups, respectively. VDZ-CDSTs groups demonstrated significant differences in the rates of clinical and endoscopic response and remission, while UST-CDST groups showed significant discrimination only for clinical remission. Although VDZ-CDSTs overestimated clinical remission rates, they more accurately predicted rates of VDZ persistence without need for surgery or dose escalation. Compared to empirically treating all patients with VDZ, VDZ-CDSTs yielded higher net benefits in selecting patients who would continue VDZ without need for surgery or dose escalation. Finally, the agreement between UST-CDST and VDZ-CDST in predicting response was 73.7%. ConclusionVDZ-CDSTs significantly discriminated response to VDZ and were more beneficial in identifying patients who would continue therapy without requiring surgery or dose escalation, compared to treating all patients empirically.

National Trends in the Creation of Diverting Ileostomy at the Time of Ileal Pouch-Anal Anastomosis in Adults With Ulcerative Colitis.

The impact of diverting ileostomy in adults with ulcerative colitis (UC) undergoing ileal pouch-anal anastomosis (IPAA) is unclear. This study uses a novel approach with population-level data to identify patients with diverting ileostomy at the time of IPAA and determine the impact of diverting ileostomy on postoperative outcomes. Using the International Business Machines (IBM) MarketScan® database, adults (18-64years old) with a diagnosis of UC who underwent IPAA between 2000 and 2019 were examined. Patients were assigned to the diverting ileostomy (DI) cohort or no-DI cohort based on the presence of an ostomy closure code in the 1-year following their IPAA. Rates of ileostomy formation and readmissions were quantified and outcomes between cohorts compared. There were 540 patients in the no-DI and 2494 in the DI cohort. There were regional differences in the rate of ostomy creation, but the overall rate of ostomy creation remained stable across years. Patients with no-DI vs DI had a longer index length of stay (LOS) (7 vs 6days, P = .001). Adverse postoperative outcomes did not differ between cohorts. Diversion did not independently affect the likelihood of a 30-day readmission, and since 2000, readmission rates have declined for all IPAA patients. This is the first study to capture population-level data on the effect of diversion at the time of IPAA for adult UC patients. This study demonstrates that the rate of fecal diversion at the time of IPAA has remained stable over time, but readmission rates have declined.

Types, behaviour and therapeutic requirements of inflammatory pouch disorders: Results from the RESERVO study of GETECCU

Background and AimsInflammatory pouch disorders exhibit a heterogeneous clinical spectrum and therapeutic requirements have not been properly studied. MethodsThis retrospective, multicentre study included ulcerative colitis patients with ileal pouch construction and were later diagnosed with an inflammatory pouch disorder between 1995 and 2020. Classifications, behaviour and therapies applied were recorded and compared in the long-term. ResultsOverall, 338 patients were recruited. The most common disorders were pouchitis (n = 258, 76%), Crohn's disease of the pouch (n = 55, 16%) and cuffitis (n = 25, 7%). Pouchitis presented mainly as chronic (65.2%) and recurrent (87%) forms. Crohn's disease manifested as stricturing/penetrating in 53% of cases and perianal disease in 42%. Patients received multiple therapies: 86% antibiotics, 42% steroids, 27% immunosuppressants, 43% biologics and 27% surgery. Compared with pouchitis, Crohn's disease of the pouch was characterised by a later diagnosis (99 vs. 55 months, p < 0.001) and greater needs for immunosuppressants (OR 3.53, 1.79–6.94, p < 0.0001), biologics (OR 5.45, 2.78–10.6, p < 0.0001) and surgeries (OR 2.65, 1.43–4.89, p < 0.001). ConclusionsChronic pouchitis is the most common pouch disorder presentation. These entities have diverse therapeutics requirements, particularly for Crohn's disease of the pouch.

Safety and Potential Efficacy of Expanded Umbilical Cord-Derived Mesenchymal Stromal Cells in Luminal Ulcerative Colitis Patients.

Inflammatory bowel disease (IBD) is characterized by periods of flare-ups and remission. It is likely to be an autoimmune in origin, presenting persistent therapeutic challenges despite current therapies. This study aims to investigate the potential of umbilical cord mesenchymal stromal cells (UCMSCs) in treating ulcerative colitis (UC). This study is a prospective phase 1 pilot, open-label, single-arm, and single-center study. UCMSCs were cultured under current Good Manufacturing Practice (cGMP) conditions and intravenously administered to six patients with UC. Safety and efficacy were evaluated using the Mayo Score/Disease Activity Index. Among the six enrolled adult patients, five completed long-term follow-ups. All exhibited at diagnosis active UC confirmed through comprehensive assessment methods. Each patient received three injections intravenously 2 weeks apart with a dose of 100 million UCMSC each. No significant short-term or intermediate-term adverse events were detected post-UCMSC administration. Long-term follow-up at 12 and 24 months showed sustained safety and no adverse events. Notably, three out of five patients achieved a Mayo score of 0 for UC, maintained at both 12 and 24 months, indicating a highly significant response (P < 0.001). This study demonstrates the safety and potential efficacy of UCMSCs in active UC. However, larger trials are warranted to validate these preliminary findings and to establish the role of UCMSC therapy as an option for managing UC.

Factors Associated With Abdominal Pain in Patients With Active and Quiescent Ulcerative Colitis: A Multicohort Study.

Abdominal pain can be an overlooked symptom in patients with ulcerative colitis (UC). The aim of this study was to investigate the prevalence and factors associated with abdominal pain in active and quiescent UC. Three study cohorts of adult UC patients were used. Cross-sectional cohorts I and II included 130 (46 active) and 288 (156 active) patients. Longitudinal cohort III included 83 patients with active disease at diagnosis that reached deep remission during follow-up. The Gastrointestinal Symptom Rating Scale was used to assess abdominal pain and other validated questionnaires to assess psychological distress, fatigue and quality of life (QoL). In the two cross-sectional cohorts, 63% and 58% of the active vs. 54% and 33% of the quiescent UC patients reported abdominal pain (both p ≤ 0.02). In the longitudinal cohort, 71% had abdominal pain at diagnosis vs. 46% when in remission (p < 0.001). In multivariable models, symptoms of anxiety were associated with higher abdominal pain levels in both cross-sectional cohorts (OR 1.75 [IQR 1.11-2.76] and OR 1.99 [1.45-2.73]), whereas in cohort II, active disease (OR 2.68 [1.61-4.45]) and female sex (OR 2.03 [1.21-3.41]) were also associated with pain. QoL was negatively correlated with higher levels of abdominal pain, both in active and quiescent disease. Abdominal pain in UC is prevalent and associated with lower QoL in both active and quiescent disease. Associated factors are active disease, female sex and psychological symptoms, especially anxiety. We suggest considering a holistic approach when treating UC patients with abdominal pain.

Tryptophan Metabolites Improve Intestinal Mucosal Barrier via the Aryl Hydrocarbon Receptor-Interleukin-22 Pathway in Murine Dextran Sulfate Sodium-Induced Pouchitis.

Pouchitis is the commonest complication after ileal pouch-anal anastomosis for ulcerative colitis. The protective effect of tryptophan metabolites on the mucosal barrier may be an effective method for treating pouchitis. The role of tryptophan metabolites on pouchitis remained unclear. We aimed to establish a murine model of dextran sulfate sodium-induced pouchitis to examine the roles of tryptophan metabolites in its pathogenesis. This is a study combined clinical patient data and animal research. A total of 22 patients were enrolled: 5 with familial adenomatous polyposis after ileal pouch-anal anastomosis, eight ulcerative colitis patients after ileal pouch-anal anastomosis patients with pouchitis, and 9 ulcerative colitis patients after ileal pouch-anal anastomosis with normal pouch. The demographic data and fecal samples of patients were collected. Male C57BL/6 mice were purchased from a licensed breeder and underwent ileal pouch-anal anastomosis to establish murine model of pouch. The bloods, feces, tissues of mice were collected. This study was performed in an academic medical center in China. The demographic data of patients were observational collected. The mice underwent ileal pouch-anal anastomosis were divided into six groups: control group with chow diet, dextran sulfate sodium, 6-formylindolo[3,2-b] carbazole + dextran sulfate sodium, high tryptophan diet + dextran sulfate sodium, CH-223191 + dextran sulfate sodium, indole-3-carboxaldehyde + dextran sulfate sodium. Animals were sacrificed after dextran sulfate sodium for 7 days. Fecal tryptophan metabolite level and microbiome composition, the severity of pouchitis, intestinal mucosal barrier function, and activation of the aryl hydrocarbon receptor-interleukin 22 pathway were assessed. Patients with pouchitis had lower fecal microbial diversity and indole-3-acetic acid levels. In murine pouchitis model, high-tryptophan diet increased fecal levels of 3-indoleglyoxylic acid, indole-3-aldehyde, and indole. A high-tryptophan diet and intraperitoneal aryl hydrocarbon receptor ligand 6-formylindolo[3,2-b] carbazole injection alleviated pouchitis. Tryptophan metabolites improved pouch mucosal barriers. aryl hydrocarbon receptor inhibitors exacerbated experimental pouchitis and disrupted the mucosal barrier; however, the aryl hydrocarbon receptor ligand indole-3-carboxaldehyde reversed this effect. This study was limited by small human sample size and lacking an Aryl hydrocarbon receptor knockout mouse model. A high-tryptophan diet and aryl hydrocarbon receptor ligand alleviated dextran sulfate sodium-induced pouchitis in murine ileal pouch-anal anastomosis model, which might be through regulating epithelial tight junctions and promoting goblet-cell differentiation, as well as maintaining the integrity and function of the mucosal barrier. This study provides a rationale for the clinical application of Aryl hydrocarbon receptor ligands in the treatment of pouchitis. See Video Abstract.

Clinical efficacy and its influencing factors of vedolizumab in the treatment of ulcerative colitis

Objective: To analyze the clinical efficacy and its influencing factors of vedolizumab (VDZ) in the treatment of ulcerative colitis (UC). Methods: The patients with moderately-to-severely active UC, who underwent VDZ treatment at the Second Affiliated Hospital of Wenzhou Medical University from November 2020 to November 2023 were retrospectively included. Based on whether 5-aminosalicylic acid (5-ASA) was used in combination with VDZ treatment, the patients were divided into combination group (received combination therapy of VDZ and 5-ASA) and monotherapy group (received monotherapy of VDZ). The clinical response rate and biological remission rate were analyzed at week 14. The clinical remission rate and mucosal healing rate were analyzed at week 38. The differences in efficacy of VDZ between the two groups were compared at week 14 and week 38, respectively. Multivariate logistic regression model was applied to analyze the influencing factors of clinical remission rate and mucosal healing rate in UC patients. Results: A total of 137 patients were included, including 74 males and 63 females, aged 18-76 (44±14) years old; Seventy-six cases in combination group and 61 cases in monotherapy group. At week 14 of VDZ treatment, the clinical response rate and biological remission rate were 79.6% (109/137) and 80.5% (33/41), respectively. At week 38, the clinical remission rate and mucosal healing rate were 78.8% (108/137) and 47.9% (57/119), respectively. There was no significant difference in clinical response rate and biological remission rate between combination group and monotherapy group at week 14 (both P>0.05). The clinical remission rate [85.5% (65/76) vs 70.5% (43/61), P=0.032] and mucosal healing rate [56.5% (39/69) vs 36.0% (18/50), P=0.027] were higher in combination group than those in monotherapy group at week 38. Multivariate logistic regression analysis showed that the combination therapy of VDZ and 5-ASA (OR=2.48, 95%CI: 1.02-6.03) and the clinical response at week 14 (OR=5.05, 95%CI: 1.98-12.85) were influencing factors of clinical remission rate of UC patients at week 38. Moreover, the baseline serum albumin (Alb) level ≥42.5 g/L was the influencing factor for the mucosal healing rate of UC patients at week 38 (OR=4.60, 95%CI: 2.06-10.24). Conclusions: VDZ is effective in treating UC patients. Both the combination of 5-ASA and the clinical response at week 14 are the influencing factors of the clinical remission rate at week 38. In addition, the baseline serum Alb level ≥42.5 g/L is the influencing factor of the mucosal healing rate at week 38.

Circulating Extracellular Matrix Products as Indicators of Disease Burden and Predictors of Disease Course in Ulcerative Colitis.

Ulcerative colitis (UC) is characterized by recurrent inflammation and challenging disease monitoring, with invasive endoscopy as the primary diagnostic tool despite the inadequacy of standard noninvasive biomarkers. This study evaluates serum extracellular matrix (ECM) fragments, which reflect the remodeling of mucosa and submucosa, as potential indicators of disease burden and treatment efficacy. We aim to determine whether serum ECM levels correlate with the extent and severity and predict treatment response. We conducted a prospective study comparing serum ECM formation (PRO-C3, PRO-C7, PRO-C11, PRO-C22), turnover (PRO-C4), and degradation markers (C1M, C3M, C4M, C7M) at Weeks 0, 12, and 24 in 49 UC patients and 50 healthy controls measured by enzyme-linked immunosorbent assay. ECM biomarkers, notably PRO-C11, differentiated UC patients from controls (area under the curve [AUC] 0.77), and PRO-C3 predicted endoscopic treatment response vs nonresponse (AUC 0.74). C7M separated moderate from severe disease in endoscopy (AUC 0.74) as well as mild from severe disease (AUC 0.84), as did the ratio C7M/PRO-C7 (AUC 0.82). Combining new and conventional markers, including hemoglobin, C-reactive protein, PRO-C3, and PRO-C22, achieved a combined AUC of 0.84 for predicting 24-week endoscopic response, adding index endoscopic activity increased the AUC to 0.92 compared to an AUC of 0.84 for endoscopy alone. Soluble ECM fragments reflect endoscopic disease severity and extent and are also predictive of therapeutic efficacy. They may as well reflect degenerative aspects of UC and may as such be future therapeutic targets aimed at prevention of intestinal damage.

RGS10 Deficiency Alleviated Intestinal Mucosal Inflammation Through Suppression of Th1/Th17 Cell Immune Responses in Ulcerative Colitis.

Regulator of G-protein signalling (RGS) 10 plays critical roles in several immune related diseases. However, whether RGS10 is involved in colonic inflammation of ulcerative colitis (UC) is still obscure. This study aimed to investigate the role of RGS10 in UC. In this study, RGS10 expression was examined by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, immunohistochemistry, and immunofluorescent analysis. Single-cell RNA sequencing of intestinal mucosa was performed to identify key immune cells with differentially expressed RGS10. RGS10 knockout mice were generated and established dextran sulphate sodium (DSS)-induced colitis. Expression of inflammatory cytokines on mRNA and protein levels was detected by qRT-PCR, enzyme-linked immunosorbent assay, and flow cytometry. We found that RGS10 expression was significantly elevated in UC patients, especially in CD4+ T cells, compared with healthy subjects. Intriguingly, RGS10 deficiency markedly alleviated DSS-induced colitis and decreased the proportion of Th1 and Th17 cells in lamina propria mononuclear cells (LPMCs), peripheral blood (PB), spleens, and mesenteric lymph nodes (mLNs). Mechanistically, RGS10 deficiency blocked the differentiation of Th1 and Th17 cells by inhibiting the phosphorylation of signal transducer and activator of transcription (STAT) 1 and STAT3. The co-immunoprecipitation analysis further showed that RGS10 could interact with protein tyrosine phosphatase non-receptor type 2 (PTPN2), and further regulated Th1 and Th17 cells differentiation of CD4+ T cells. In conclusion, RGS10 deficiency alleviated intestinal mucosal inflammation through inhibition of Th1/Th17 cell-mediated immune responses via interaction with PTPN2 in CD4+ T cells. Therefore, targeting RGS10 may represent a novel therapeutic approach for UC treatment.

Revealing Fibrosis Genes as Biomarkers of Ulcerative Colitis: A Bioinformatics Study Based on ScRNA and Bulk RNA Datasets.

This study aimed to uncover biomarkers associated with fibroblasts to diagnose ulcerative colitis (UC) and predict sensitivity to TNFα inhibitors. We identified fibrosis-related genes by analyzing eight bulk RNA and one single-cell RNA sequencing dataset from UC patients. Three machine learning algorithms were employed to identify common significant genes. We utilized five machine learning models, namely Random Forest (RF), Support Vector Machine (SVM), Xgboost, Multilayer Perceptron (MLP), and Logistic Regression, to develop diagnostic models for UC. Following hyperparameter tweaking using grid search, we evaluated Matthew's Correlation Coefficient (MCC) of each model on the validation set. Finally, we identified five hub genes in UC patients and evaluated their response to infliximab or golimumab. We identified 23 genes associated with fibroblasts. Further analysis using three ML models revealed BIRC3, IFITM2, ANXA1, ISG20, and MSN as critical fibroblast genes. Following hyperparameter adjustment, the SVM model exhibited the most favorable characteristics in the validation set, achieving an MCC of 0.7. ANXA1 contributed the most to the model that predicts UC. The optimal model was implemented on the website. Among UC patients receiving TNFα inhibitor treatment, the ineffective group showed considerably increased expression of the five critical genes than the responsive group. BIRC3, IFITM2, ANXA1, ISG20, and MSN may serve as potential diagnostic biomarkers in UC. Through the interaction between characteristic biomarkers and immune infiltrating cells, the immune response mediated by these characteristic biomarkers plays a crucial role in the occurrence and development of UC.

Factors influencing the discontinuation of biologic therapies in patients with ulcerative colitis

BackgroundThe therapeutic landscape for ulcerative colitis (UC) has recently broadened to include anti-TNFα, anti-integrin, and anti-IL-12/23p40 antibody agents. These biological agents are tailored to individual patient profiles. However, some patients cease biological treatment. This study investigates factors influencing the discontinuation of biological treatment in UC patients.MethodsThis retrospective single-cohort study encompasses UC patients who commenced treatment with biological agents like infliximab, adalimumab, golimumab, vedolizumab, and ustekinumab from April 2019 to March 2022. Patients were categorized into continuation and discontinuation groups based on their one-year treatment status. Baseline characteristics were compared between the groups.ResultsOf the 116 UC patients, 102 were included in the study. Among these, 74 (72.5%) continued and 28 (27.5%) discontinued biological therapy. Discontinuation rates for infliximab, adalimumab, golimumab, vedolizumab, and ustekinumab were 33.3%, 25.0%, 50.0%, 30.2%, and 15.6%, respectively. The primary discontinuation reason was lack of efficacy (85.7%), followed by adverse events (7.1%), pregnancy (3.6%), and death (3.6%). The discontinuation group had a significantly lower rate of concomitant thiopurine compared to the continuation group (28.6% vs. 56.8%, p = 0.0132). Multivariable analysis revealed that concomitant thiopurine was independently associated with therapy continuation (p = 0.0075).ConclusionThe study indicates that concomitant thiopurine significantly correlates with the continuation of biological therapies in UC patients, underscoring the importance of concomitant thiopurine in sustaining biological therapy. Further studies are warranted to assess the efficacy of combination therapy.

The value of assessing deep disease healing by probe-based confocal laser endomicroscopy and histology for long-term prognosis of ulcerative colitis.

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.

Efficacy of Second-Line Biological Therapies in Moderate to Severe Ulcerative Colitis Patients with Prior Failure of Anti-Tumor Necrosis Factor Therapy: A Multi-Center Study.

Few studies have compared the efficacy and safety of second-line biological therapies in ulcerative colitis (UC) patients with prior exposure to anti-tumor necrosis factor (TNF) therapy. We aim to compare the efficacy and safety between ustekinumab, vedolizumab, and tofacitinib, a current option as second-line biological therapy with different mechanisms in those patients. This retrospective multi-center study was conducted across five institutions from 2011 to 2022. We enrolled patients with moderate to severe UC who failed anti-TNF therapy and subsequently received ustekinumab, vedolizumab, or tofacitinib as second-line biological therapy. The outcomes were analyzed for clinical response/remission and endoscopic improvement/remission rates after induction therapy, drug persistency, and adverse events. A total of 70 UC patients were included and grouped into ustekinumab (11 patients), vedolizumab (40 patients), and tofacitinib (19 patients) treatments. The clinical response/remission rates after induction therapy were similar between ustekinumab (90.9/81.8%), vedolizumab (92.5/65.0%), and tofacitinib (94.7/73.7%). There were no significant differences in the endoscopic improvement/remission rates between the three groups: 90.9/18.2% for ustekinumab, 72.5/12.5% for vedolizumab, and 84.2/26.3% for tofacitinib. Drug persistence was similar across the three agents (p = 0.130). Three patients of the tofacitinib group experienced adverse events (herpes zoster and hypertriglyceridemia). Based on real-world data, second-line biological therapy with ustekinumab, vedolizumab, and tofacitinib showed comparable efficacy in patients with moderate to severe UC with prior exposure to anti-TNF therapy.

Predictive Value of PHRI for Recurrence within One Year after UC Treatment: A Retrospective Study.

Aims/Background Accurate prediction of recurrence after treatment is crucial for controlling the progression and improving the prognosis of active ulcerative colitis (UC) patients. Previous studies have evaluated the therapeutic response in UC patients by assessing mucosal healing, using measures such as the Paddington International Virtual ChromoendoScopy Score (PICaSSO) and the PICaSSO Histological Remission Index (PHRI). The PHRI is effective for evaluating treatment response and disease control in UC patients, but its predictive value for short-term recurrence has not been reported in the literature. Therefore, this retrospective analysis of clinical data aims to explore the predictive value of the PHRI and provide a reference for improving the prognosis of UC patients. Methods Clinical data of UC patients in clinical remission admitted to our hospital from June 2017 to June 2023 were retrospectively collected. Patients were divided into the recurrence group and the non-recurrence group, based on whether they experienced recurrence during the one-year follow-up. Clinical data, laboratory test results, and PHRI scores were collected. Variables that showed statistically significant differences between groups in univariate analysis were included in multivariate logistic regression analysis. The predictive value of PHRI was analyzed with receiver operating characteristic (ROC) curve analysis. Results One hundred and two UC patients in the clinical remission stage were included in this study, and there were no cases of loss to follow-up. Among them, 36 patients (35.29%) experienced recurrence within the one-year follow-up, whereas 66 patients (64.71%) did not. Compared with the non-recurrence group, the recurrence group had a more number of cases with lesions in the left-sided colon and extensive colon, higher percentages of cases that were moderate or severe, and a significantly higher colonoscopy score (p < 0.05). Compared with the non-recurrence group, the PHRI score of the recurrence group was significantly higher (p < 0.001). Multivariate logistic regression analysis showed that that the lesion range (OR = 4.127, p = 0.005), disease severity (OR = 3.889, p = 0.019), colonoscopy score (OR = 6.128, p < 0.001), and PHRI score (OR = 5.466, p < 0.001) were independent risk factors for recurrence in UC patients. The results of ROC curve analysis showed that the area under the curve of the PHRI score in predicting the recurrence of UC patients was 0.838 (95% CI: 0.760-0.916). When the optimal cut-off value was 1 point, the sensitivity and specificity were the highest, which were 89.58% and 65.58%, respectively, indicating that PHRI score had good predictive value. Conclusion The lesion extent, disease severity, endoscopic score, and PHRI score are associated with recurrence within one year in UC patients in the clinical remission stage, and the PHRI score has good predictive value.

Neutrophil Extracellular Traps in Pediatric Inflammatory Bowel Disease: A Potential Role in Ulcerative Colitis.

Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory condition of the gut affecting both adults and children. Neutrophil extracellular traps (NETs) are structures released by activated neutrophils, potentially contributing to tissue damage in various diseases. This study aimed to explore the presence and role of NETs in pediatric IBD. We compared intestinal biopsies and peripheral blood from 20 pediatric IBD patients (UC and CD) to controls. Biopsy staining and techniques for neutrophil activation were used to assess neutrophil infiltration and NET formation. We also measured the enzymatic activity of key NET proteins and evaluated NET formation in UC patients in remission. Both UC and CD biopsies showed significantly higher levels of neutrophils and NETs compared to controls (p < 0.01), with UC exhibiting the strongest association. Peripheral blood neutrophils from UC patients at diagnosis displayed increased NET formation compared to controls and CD patients. Interestingly, NET formation normalized in UC patients following remission-inducing treatment. This pilot study suggests a potential role for NETs in pediatric IBD, particularly UC. These findings warrant further investigation into the mechanisms of NET involvement and the potential for targeting NET formation as a therapeutic strategy.

Comparison of the Gut Microbiota of Patients Who Improve with Antibiotic Combination Therapy for Ulcerative Colitis and Those Who Do Not: Investigation by Fecal Metagenomic Analyses.

Background/Objectives: The cause of ulcerative colitis (UC) may be related to commensal bacteria in genetically susceptible patients. We previously demonstrated that triple antibiotic combination therapy induces remission in patients with active UC in randomized controlled trials (RCTs). Now, we investigate changes in the gut microbiota of patients who responded to the antibiotic combination therapy. Methods: Thirty-one patients with UC given ATM/AFM (amoxicillin, metronidazole, and tetracycline or fosfomycin) therapy for two weeks were enrolled in this study. The clinical conditions of these UC patients were evaluated by the partial Mayo score. The gut microbiota was compared via the metagenomic shot gun analysis of fecal samples. Results: Of the 31 patients, 16 and 8 experienced complete and partial remission, respectively, over three months in response to ATM/AFM therapy, whereas ATM/AFM showed no efficacy in 7 patients. The dysbiosis before treatment in the active stage could be associated with increased populations of Bacteroides, Parabacteroides, Rickenella, Clostridium, Flavonifractor, Pelagibacter, Bordetella, Massilia, and Piscrickettsia species. Metagenomic analysis revealed dramatic changes in the gut microbiota at an early stage, that is, just two weeks after starting ATM/AFM therapy. After treatment in the responder group, the populations of bifidobacterium and lactobacilli species were significantly increased, while the population of bacteroides decreased. Conclusions: These results suggest that metagenomic analysis demonstrated a marked change in the gut microbiota after antibiotic combination treatment. In the triple antibiotic combination therapy, remission was associated with an increase in bifidobacterium and lactobacilli species.

Patient preferences for advanced therapies in ulcerative colitis using conjoint analysis.

Selecting an optimal advanced therapy for ulcerative colitis (UC) is difficult because of the increasing number of available therapies. This study assessed UC patients' preferences for drug profiles in decision-making regarding advanced therapies using conjoint analysis. A web-based survey was conducted from October to November 2023 in patients with UC aged ≥ 18 years with prior oral 5-aminosalicylic acid treatment (UMIN000052327). We quantified the importance of drug attributes (location of administration, route/frequency of administration, speed of onset-of-action, maintenancesustainability, risk of serious adverse events within 1 year, and novelty of the drug) and the part-worth utility of attribute levels in mild and severe symptom scenarios, including among employed versus unemployed patients. Of 372 patients who completed the survey, 365 were evaluated. Patient preferences were generally highly individualized. The route/frequency of administration was the most important attribute in both the mild and severe symptom scenarios. Oral administration was preferred in the mild symptom scenario, whereas no specific preference was observed in the severe symptom scenario. The route/ frequency of administration was more valued in the mild symptom scenario than in the severe one, whereas speed of onset of action was more valued in the severe symptom scenario. No significant difference was found in the preference for drug profiles between employed and unemployed patients. Patient preferences for the route/frequency of administration, as well as other drug profiles, change with disease severity but demonstrate substantial interindividual variability. Therefore, shared decision-making is important to incorporate patients' perspectives into the selection of advanced therapies.

Comparative Value of CRP and FCP for Endoscopic and Histologic Remissions in Ulcerative Colitis.

Aim: We have previously shown that CRP < 2.9 mg/L is a better predictor of endoscopic remission (ER) than CRP < 5 mg/L in ulcerative colitis (UC). Here, we prospectively evaluate CRP and FCP cut-offs and compare them in predicting ER and histological remission (HR) in UC. Method: One hundred thirty-five steroid-free UC patients were evaluated prospectively. ER was defined as Mayo endoscopic sub-score 0-1. In colonoscopy, the colon was evaluated as seven segments: rectum, sigmoid, descending, proximal-transverse, distal-transverse, ascending colon, and cecum. Two biopsies of each segment were evaluated for histological inflammation and graded using the Nancy and Geboes scores. All segment biopsies with Nancy < 1 and Geboes < 2 were defined as HR. Results: The optimum cut-off values for FCP and CRP were 120 μg/g and 2.75 mg/L for ER, respectively. AUC values of FCP and CRP were similar for ER and Mayo-0 disease in ROC analysis. CRP and FCP also had similar performances with these cut-offs regarding ER. While CRP was a predictor to assess the extensiveness of active UC, FCP was not. ROC analysis showed no difference between CRP and FCP regarding HR. Cut-off values for HR were 2.1 mg/L and 55 μg/g for CRP and FCP, respectively. CRP and FCP, in combination with the mentioned cut-off values, detected ER and HR in nearly 2/3 and ½ of the patients, respectively, with high specificity. Conclusions: Reappraised CRP (ER: 2.75 mg/L, HR: 2.1 mg/L) has as much diagnostic contribution as relevant FCP in predicting ER and HR and contributes more to revealing the proximal extension in active colitis compared to FCP. Relevant CRP and FCP combinations may improve the prediction rates.

Cost-effectiveness and cost-utility of optimized mercaptopurine treatment versus placebo in ulcerative colitis patients: The randomized controlled OPTIC trial.

We assessed the cost-effectiveness and cost-utility of therapeutic drug monitoring (TDM)-guided mercaptopurine treatment compared with placebo in ulcerative colitis (UC) patients failing 5-aminosalicylates. Data were gathered alongside the randomized controlled OPTIC trial (EudraCT: 2015-005260-41). The evaluation was performed from a health care and societal perspective as cost-effectiveness and cost-utility analyses with a time horizon of one year. Volumes and costs of in-hospital care, out-of-hospital care, out-of-pocket expenses and productivity loss were assessed. The main outcomes were the extra costs per additional patient who achieved clinical remission and endoscopic improvement at 52weeks (responders) and extra costs per quality-adjusted life-year (QALY) gained. In total, 59 patients were randomized to the intervention (n=29) and control (n=30) group. Non-significant differences in costs were €63 (-€1267 to €1434; P=0.93) in favour of placebo from a health care perspective and -€742 (-€3683 to €2016; P=0.64) in favour of mercaptopurine from a societal perspective. The higher proportion of responders and a non-significant QALY difference of 0.0475 (-0.024-0.117) (P=0.184) favouring patients on mercaptopurine treatment resulted in €165 extra costs per additional responder and €1326 extra costs per QALY gained from a health care perspective. From a societal perspective, dominance over placebo was observed with cost savings of €1937 per additional responder and €15,621 per QALY gained. The probability of optimised mercaptopurine treatment being cost-effective was 0.80 at a willingness to pay per additional QALY of €20,000. TDM-based mercaptopurine treatment in UC patients failing 5-aminosalicylates is a cost-effective strategy from a societal perspective.