Published papers

Background and objective: Leucine-rich alpha-2 glycoprotein (LRG) is a novel biomarker for Crohn’s disease (CD). The utility of combination use of LRG and C-reactive protein (CRP) has not been reported. This study aimed to investigate the diagnostic performance of LRG in combination with CRP to predict endoscopic activity. Methods: A single-centre, retrospective, cross-sectional study was conducted. Patients with CD who had serum LRG concentrations measured at least once between June 2020 and May 2021 were enrolled. Clinical activity was evaluated with the Harvey–Bradshaw Index (HBI). Spearman’s rank correlation coefficient (rs) was used to analyse the correlations between the HBI, LRG concentrations and CRP concentrations. In patients undergoing ileocolonoscopy or balloon-assisted enteroscopy within 60 days before or after LRG measurement, endoscopic activity was evaluated with the simple endoscopic score for Crohn’s disease (SES-CD). The diagnostic performance of LRG and CRP for endoscopic activity was evaluated using receiver operating characteristic (ROC) analysis. Results: Four hundred and eighty-nine measurements in 343 patients were analysed. Although a strong correlation was found between LRG and CRP concentrations (rs = 0.75), the HBI did not well correlate with LRG or CRP concentrations. Endoscopic activity was analysed in 56 patients. In diagnosing endoscopically moderate to severe activity (SES-CD > 6), the area under the ROC curve of LRG was greater than that of CRP (0.74 vs. 0.63; p = .037). The optimal cut-off value estimated by Youden’s index was 15.5 µg/mL for LRG, and 0.13 mg/dL for CRP. LRG and CRP concentrations were considered positive when they were above these cut-off values, and the sensitivity and specificity for an SES-CD > 6 were 58.3% and 93.8%, respectively. Dual positivity of LRG and CRP showed the highest specificity. Conclusions: Combination use of dual positive LRG and CRP is useful for diagnosing endoscopically moderate to severe disease.

Abstract – Introduction: Serum leucine-rich alpha-2 glycoprotein (LRG) has emerged as a novel biomarker for inflammatory bowel disease (IBD). However, its clinical utility among non-Japanese populations has not been investigated. This study aimed to validate the diagnostic ability of serum LRG in non-Japanese patients with IBD. Methods: A retrospective cross-sectional study was conducted, including patients with IBD who underwent at least one serum LRG measurement between 2020 and 2023. Correlations between serum LRG and C-reactive protein (CRP) levels were independently evaluated in Japanese and non-Japanese cohorts. The association between endoscopic activity and serum LRG levels was investigated, and the diagnostic performance of LRG for detecting endoscopic activity was evaluated using receiver operating characteristic (ROC) analysis. Results: Serum LRG levels were measured at 11, 730 time points for 2, 500 Japanese patients and 276 time points for 58 non-Japanese patients. Among non-Japanese patients, 53% were Asian, 37% White, 4% Black, and 6% other racial backgrounds. The correlation between LRG and CRP was similarly robust in non-Japanese (r = 0.64) and Japanese (r = 0.64) patients. Among non-Japanese, serum LRG levels in endoscopic remission were significantly lower than those in active disease (p = 0.0228). The area under the ROC curve of LRG for endoscopically active disease in ulcerative colitis (n = 46) was 0.79 (95% confidence interval [CI], 0.60–0.98), numerically higher than that of CRP at 0.69 (95% CI, 0.55–0.84). Conclusion: Serum LRG demonstrates consistent diagnostic value in both Japanese and non-Japanese patients with IBD, supporting its broader clinical applicability across diverse populations.

Short bowel syndrome (SBS) is a life-threatening condition in which outcomes often critically depend on ileal function, the only intestinal segment specialized for bile acid uptake and efficient fat absorption. However, whether restoring ileal epithelium-specific nutrient absorption can ameliorate SBS has remained unknown. Here, we demonstrate a niche-preserving transplantation strategy enabling highly efficient engraftment of intestinal organoids into the rat small intestine. Clearing luminal mucus with N-acetylcysteine facilitates ethylenediaminetetraacetic acid (EDTA)-based epithelial detachment, enabling removal of Lgr5+ stem cells while preserving the stromal niche. This preconditioning increased the engrafted area and enabled the generation of an ilealized jejunum that improved body-weight trajectories and survival in rat SBS. Furthermore, the engrafted epithelia endowed the jejunum with bile acid absorption capacity. These findings provide in vivo evidence for stem cell niche theory, showing that the niche is essential to accommodate donor stem cells, and establish ilealized jejunum as a path toward autologous, region-targeted therapy for SBS.

Primary sclerosing cholangitis (PSC) is frequently accompanied by colitis with clinicopathologic features that differ from conventional inflammatory bowel disease (IBD). Accumulating evidence indicates that PSC-associated IBD (PSC-IBD) often presents as extensive colitis with a right-sided predominant distribution and characteristic endoscopic features, such as rectal sparing and backwash ileitis. Beyond endoscopic appearance, PSC-IBD also appears to have distinct biological underpinnings, including shared genetic susceptibility, dysregulated bile acid signaling, altered gut microbial communities, and immune crosstalk along the gut–liver axis. These mechanisms may contribute not only to intestinal inflammation but also to PSC-related clinical outcomes. From a long-term perspective, patients with PSC and colitis are consistently classified as a high-risk group for colorectal neoplasia, warranting early and intensive colonoscopic surveillance. In parallel, surveillance for hepatobiliary malignancies remains central in PSC care, although risk stratification continues to evolve. Therapeutic management generally follows established IBD algorithms, yet the extent to which colitis-directed therapies modify PSC outcomes remains uncertain, with heterogeneous findings across cohorts and endpoints. In this review, we summarize current knowledge on the clinical phenotype, mechanistic framework, and outcome-driven management of PSC-IBD, and highlight future directions toward precision surveillance and mechanism-based interventions targeting bile acid–microbiota–immune interactions.

Objectives: Despite recent advances in endoscopic equipment and diagnostic techniques, early detection of ulcerative colitis-associated neoplasia (UCAN) remains difficult because of the complex background of the inflamed mucosa of ulcerative colitis and the morphologic diversity of the lesions. We aimed to describe the main diagnostic patterns for UCAN in our cohort, including lateral extension surrounding flat lesions. Methods: Sixty-three lesions in 61 patients with flat-type dysplasia that were imaged with dye chromoendoscopy (DCE) were included in this analysis. These DCE images were analyzed to clarify the dye-chromoendoscopic imaging characteristics of flat dysplasia, and the lesions were broadly classified into dysplastic and nondysplastic mucosal patterns. Results: Dysplastic mucosal patterns were classified into two types: small round patterns with round to roundish structures, and mesh patterns with intricate mesh-like structures. Lesions with a nondysplastic mucosal pattern were divided into two major types: a ripple-like type and a gyrus-like type. Of note, 35 lesions (55.6%) had a small round pattern, and 51 lesions (80.9%) had some type of mesh pattern. About 70% of lesions with small round patterns and 49% of lesions with mesh patterns were diagnosed as high-grade dysplasia or carcinoma, while about 30% of lesions with small round patterns and 51% of lesions with mesh patterns were diagnosed as low-grade dysplasia. Conclusion: When a characteristic mucosal pattern, such as a small round or mesh pattern, is found by DCE, the possibility of UCAN should be considered.

Objectives: Ulcerative colitis-associated neoplasia (UCAN) often presents as flat-type dysplasia that is difficult to characterize endoscopically. We developed a FOCUS (Flat-type dysplasia Optical assessment by Chromoendoscopy in Ulcerative colitiS) classification and evaluated its diagnostic performance and reproducibility. Methods: This single-center retrospective study included 33 UCAN lesions from 26 patients. Prospectively recorded FOCUS classifications at 230 biopsy sites were compared with histopathology. Chromoendoscopic patterns were categorized as Type I (“suggestive of non-dysplasia,”), Type II (“suggestive of dysplasia with low confidence”), or Type III (“suggestive of dysplasia with high confidence”). Diagnostic performance was assessed using two prespecified thresholds: Types II/III versus Type I and Type III versus Types I/II. Eight endoscopists independently classified all images; interobserver and intraobserver agreement were assessed using Fleiss' and Cohen's κ, respectively. Results: The dysplasia-bearing rate increased stepwise from Type I to Type III (Type I 15.5%, Type II 58.3%, Type III 81.8%). Using the primary threshold, sensitivity was 82.0%, and specificity 75.4% (positive likelihood ratio 3.33; negative likelihood ratio 0.24). Interobserver agreement for the three-category classification was moderate to substantial (Fleiss' κ 0.629; 95% CI 0.545–0.712), and median intraobserver agreement was substantial (Cohen's κ 0.738). Conclusions: The FOCUS classification provides clinically meaningful risk stratification for flat-type dysplasia in a high-risk UCAN cohort, with acceptable interobserver and intraobserver reproducibility.

The intestinal epithelium is maintained by stem cells that balance self-renewal and differentiation to sustain homeostasis and enable regeneration after injury. Recent advances—including organoid culture, genome editing, orthotopic xenotransplantation, and somatic mutation–based analysis—have created new opportunities to investigate intestinal stem cell (ISC) dynamics in humans. These studies have revealed striking species-specific differences: whereas mouse LGR5+ ISCs divide daily and are chemo-sensitive, human colonic LGR5+ stem cells are predominantly slow-cycling and chemo-resistant. Consistent with this reduced cycling, human ISCs accumulate somatic mutations more slowly than those of mice. Across mammals, ISC proliferation rates inversely correlate with lifespan, a relationship thought to minimize mutation accumulation and reduce cancer risk, in line with Peto's paradox. Regenerative responses in both mice and humans can involve fetal-like reprogramming driven by YAP and other signaling pathways, yet the extent of species differences in intestinal regenerative capacity remains unclear. This review synthesizes current insights into ISC kinetics, injury responses, and evolutionary adaptations, highlighting the need for human-focused studies to bridge translational gaps and guide regenerative medicine strategies.

Introduction: Intestinal endometriosis is a benign condition characterized by the presence of endometrial tissue within the bowel wall, often mimicking colorectal malignancy. Its coexistence with ulcerative colitis (UC) is rare and can complicate the diagnosis. Case Presentation: A 35-year-old woman with long-standing UC presented with severe diarrhea and rectal bleeding. Colonoscopy revealed severe disease activity with multiple deep ulcerations and a newly developed stricture in the sigmoid colon. Pathological examinations, including bite-on-bite biopsies, showed no evidence of malignancy. However, colitis-associated neoplasia (CAN) could not be completely ruled out because such lesions may primarily involve the deep layers of the colonic wall. Given the severity of disease and concern for possible CAN, a total colectomy was performed. Histopathological and immunohistochemical analysis of the resected specimen ultimately identified intestinal endometriosis as the cause of the stricture. Conclusion: This case underscores the importance of considering intestinal endometriosis in women with UC who develop unexplained colonic strictures, particularly when malignancy cannot be confirmed.

Background: Computed tomography colonography (CTC) is increasingly utilized for the evaluation of colorectal neoplasms. However, in patients with ulcerative colitis (UC), current European Crohn’s and Colitis Organisation guidelines recommend CTC only for limited indications, such as the presence of strictures. This study aimed to assess the potential clinical utility of CTC by examining its detectability of UC-associated neoplasia (UCAN) lesions. Methods: This single-center, retrospective observational study included consecutive patients with UC who underwent preoperative CTC and were scheduled for pancolectomy for UCAN between January 2014 and June 2024. Lesion detectability on CTC was assessed in comparison with endoscopic findings, histopathological tumor depth, and morphological characteristics. Multivariable logistic regression was performed to identify factors associated with detectability on CTC. Results: Among 50 patients with 71 histologically confirmed lesions, 49% (35/71) were detectable by CTC. Detection was highest in advanced cancer (100%, 7/7), sessile (80%, 4/5) and depressed (80%, 8/10) morphologies, and lower in non-polypoid types such as superficial elevated (58%, 14/24) and flat (8%, 2/25) lesions. Detection by depth was 29% (12/42) for intramucosal, 75% (9/12) for submucosal, 100% (5/5) for muscularis propria, 73% (8/11) for subserosa/adventitia, and 100% (1/1) for serosal lesions. Flat morphology (adjusted odds ratio [aOR], 0.06; 95% confidence interval [CI], 0.01-0.27) and intramucosal invasion (aOR, 0.10; 95% CI, 0.02-0.46) were independently associated with non-detection. Conclusions and Relevance: Despite preoperative awareness of UCAN, CTC demonstrated limited sensitivity. While CTC may serve a complementary role in selected cases, endoscopy remains essential for comprehensive lesion detection.

Background: Endoscopic resection (ER) is increasingly utilized for ulcerative colitis-associated neoplasias (UCANs); however, these lesions demonstrate higher rates of local residuals and recurrences compared with sporadic neoplasias. This may be partly explained by challenges in accurately delineating lesion borders preoperatively, though their clinicopathologic features remain incompletely understood. Objectives: This study aimed to characterize the endoscopic and histologic features associated with local residuals and recurrences following ER for UCAN. Design: A retrospective observational study. Methods: Patients diagnosed with UCAN exhibiting a p53 mutation pattern between 2005 and 2024 and suspected of having local residual or recurrent lesions after ER were included. Endoscopic and histologic features were evaluated. Results: Of 122 UCAN patients, 13 (6 underwent initial ER at our institution before 2018, and 7 underwent initial ER elsewhere) were identified with suspected local residuals or recurrences. Prior to initial ER, p53 immunostaining was not performed in eight cases (five without biopsy and three with biopsy specimens not stained), and only two patients underwent biopsy of the surrounding tissue. Ten tumors had positive or potentially positive horizontal margins (HMs) that were not identified endoscopically at the time of ER. All local recurrences were associated with suspected positive HMs, with a median time to recurrence of 16.5 (8.5–23.8) months. At recurrence, 50% of the lesions appeared flat, while the remaining 50% were superficial elevated lesions with adjacent flat dysplasia. Conclusion: Inadequate preoperative assessment of the horizontal extent of UCANs may contribute to residual or recurrent disease after ER. Comprehensive evaluation—including p53 immunostaining and careful inspection for surrounding flat dysplasia—may improve curative outcomes in UCAN management.

Background: Despite the availability of several biologics for ulcerative colitis (UC), there remains a critical need to identify first-line treatment biologics. The superiority of infliximab (IFX) over vedolizumab (VED) and ustekinumab (UST) was evaluated as initial UC treatments in patients with biologic-naïve UC. Methods: This multicenter, randomized control trial was conducted across 20 Japanese medical institutions. An independent center randomly allocated patients with UC (Mayo score ≥ 6) who had not previously used biologics to three treatment groups (IFX, VED, UST). The primary endpoint was the clinical remission (CR) rate at week 12, with other endpoints including the treatment continuation rate at week 26 and adverse events (AEs). Results: From May 2021 to June 2023, 107 cases were registered, including 104 for safety and 97 for efficacy evaluation. CR rate at week 12 was 36.4% (95%CI:20.4–54.9), 32.4% (95%CI:17.4–50.5) and 43.3% (95%CI:25.5–62.6) in IFX, VED, and UST group, respectively. Continuation rates at week 26 were 50.0%(IFX), 58.3% (VED), and 82.4% (UST). AEs related to study medication were 14.7% (IFX), 16.7% (VED), and 5.9% (UST). Predictors for CR at week 12 were thiopurine use in IFX (p = 0.04), lower baseline Mayo score (p = 0.007), and lower Patient report outcome 2 (p = 0.003) at week 2 in VED. Conclusion: Due to small sample size, it is challenging to make conclusions for main endpoints from this study while our study suggested that use of thiopurines in IFX group and lower activity at enrollment in VED group may enhance treatment efficacy. (jRCT1031200329; available at https://jrct.niph.go.jp/).

BACKGROUND: Research on whether gastrointestinal symptoms correlate with the severity of Coronavirus Disease 2019 (COVID-19) has been inconclusive. This study aimed to clarify any associations between gastrointestinal symptoms and the prognosis of COVID-19. METHODS: We collected data from the Japanese nationwide registry for COVID-19 to conduct a retrospective cohort study. Data from 3498 Japanese COVID-19 patients, diagnosed at 74 facilities between February 2020 and August 2022, were analyzed in this study. Hospitalized patients were followed up until discharge or transfer to another hospital. Outpatients were observed until the end of treatment. Associations between gastrointestinal symptoms and clinical outcomes were investigated using multivariable-adjusted logistic regression models. RESULTS: The prevalence of diarrhea, nausea/vomiting, abdominal pain, and melena were 16.6% (581/3498), 8.9% (311/3498), 3.5% (121/3498), and 0.7% (23/3498), respectively. In the univariable analysis, admission to intensive care unit (ICU) and requirement for mechanical ventilation were less common in patients with diarrhea than those without (ICU, 15.7% vs. 20.6% (p = 0.006); mechanical ventilation, 7.9% vs. 11.4% (p = 0.013)). In the multivariable-adjusted analysis, diarrhea was associated with lower likelihood of ICU admission (adjusted odds ratio (aOR), 0.70; 95% confidence interval (CI), 0.53-0.92) and mechanical ventilation (aOR, 0.61; 95% CI, 0.42-0.89). Similar results were obtained in a sensitivity analysis with another logistic regression model that adjusted for 14 possible covariates with diarrhea (ICU; aOR, 0.70; 95% CI, 0.53-0.93; mechanical ventilation; aOR 0.62; 95% CI, 0.42-0.92). CONCLUSIONS: Diarrhea was associated with better clinical outcomes in COVID-19 patients.

Although the main cellular target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is thought to be alveolar cells, the absence of their tractable culture system precludes the development of a clinically relevant SARS-CoV-2 infection model. Here, we establish an efficient human alveolosphere culture method and sphere-based drug testing platform for SARS-CoV-2. Alveolospheres exhibit indolent growth in a Wnt- and R-spondin-dependent manner. Gene expression, immunofluorescence, and electron microscopy analyses reveal the presence of alveolar cells in alveolospheres. Alveolospheres express ACE2 and allow SARS-CoV-2 to propagate nearly 100,000-fold in 3 days of infection. Whereas lopinavir and nelfinavir, protease inhibitors used for the treatment of human immunodeficiency virus (HIV) infection, have a modest anti-viral effect on SARS-CoV-2, remdesivir, a nucleotide prodrug, shows an anti-viral effect at the concentration comparable with the circulating drug level. These results demonstrate the validity of the alveolosphere culture system for the development of therapeutic agents to combat SARS-CoV-2.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the disease COVID-19 can lead to serious symptoms, such as severe pneumonia, in the elderly and those with underlying medical conditions. While vaccines are now available, they do not work for everyone and therapeutic drugs are still needed, particularly for treating life-threatening conditions. Here, we showed nasal delivery of a new, unmodified camelid single-domain antibody (VHH), termed K-874A, effectively inhibited SARS-CoV-2 titers in infected lungs of Syrian hamsters without causing weight loss and cytokine induction. In vitro studies demonstrated that K-874A neutralized SARS-CoV-2 in both VeroE6/TMPRSS2 and human lung-derived alveolar organoid cells. Unlike other drug candidates, K-874A blocks viral membrane fusion rather than viral attachment. Cryo-electron microscopy revealed K-874A bound between the receptor binding domain and N-terminal domain of the virus S protein. Further, infected cells treated with K-874A produced fewer virus progeny that were less infective. We propose that direct administration of K-874A to the lung could be a new treatment for preventing the reinfection of amplified virus in COVID-19 patients.

Inflammatory bowel disease (IBD) is a chronic relapsing-remitting inflammatory disease of the gastrointestinal tract with an unknown etiology, and its incidence is increasing worldwide. Recent advances in immunomodulatory therapeutic agents such as biologics and small-molecule inhibitors have improved the prognosis of patients with IBD. However, some patients are refractory and resistant to these immunomodulatory therapies, and new therapies are needed. Given the importance of the intestinal epithelium in IBD pathogenesis, the difficulty of culturing intestinal epithelial cells (IECs) for long periods remains an obstacle in IBD research. Over the past 15 years, intestinal stem cells have been identified, and the in vivo microenvironment, called the niche, required for their maintenance has been elucidated, making the permanent culture of IECs possible. Recapitulating the niche in vitro, the intestinal epithelium forms 3-dimensional structures called organoids that simulate the intestinal epithelium in vivo. The intestinal epithelium plays an important role in the intestinal barrier and immunomodulatory functions and serves as a physical structure that separates the intestinal lumen from the body. Recent studies have revealed that functional disruption of the intestinal epithelium is closely related to the pathogenesis of IBD, and IBD research using organoids has attracted attention. In this review, we discuss the application of adult tissue-derived organoids culture technology to elucidate the pathogenesis of IBD and to develop novel therapies, including regenerative treatments.

Radiation enteritis (RE) is a prevalent complication of radiotherapy for pelvic malignant tumors, characterized by severe intestinal epithelial destruction and progressive submucosal fibrosis. However, little is known about the pathogenesis of this disease, and so far, there is no specific targeted therapy. Here, we report that CXCL16 is upregulated in the injured intestinal tissues of RE patients and in a mouse model. Genetic deletion of Cxcl16 mitigates fibrosis and promotes intestinal stem cell-mediated epithelial regeneration after radiation injury in mice. Mechanistically, CXCL16 functions on myofibroblasts through its receptor CXCR6 and activates JAK3/STAT3 signaling to promote fibrosis and, at the same time, to transcriptionally modulate the levels of BMP4 and hepatocyte growth factor (HGF) in myofibroblasts. Moreover, we find that CXCL16 and CXCR6 auto- and cross-regulate themselves in positive feedback loops. Treatment with CXCL16 neutralizing monoclonal antibody attenuates fibrosis and improves the epithelial repair in RE mouse model. Our findings emphasize the important role of CXCL16 in the progression of RE and suggest that CXCL16 signaling could be a potential therapeutic target for RE. © 2022 The Pathological Society of Great Britain and Ireland.

Background & Aims: In the mouse intestinal epithelium, Lgr5+ stem cells are vulnerable to injury, owing to their predominantly cycling nature, and their progenies de-differentiate to replenish the stem cell pool. However, how human colonic stem cells behave in homeostasis and during regeneration remains unknown. Methods: Transcriptional heterogeneity among colonic epithelial cells was analyzed by means of single-cell RNA sequencing analysis of human and mouse colonic epithelial cells. To trace the fate of human colonic stem or differentiated cells, we generated LGR5-tdTomato, LGR5-iCasase9-tdTomato, LGR5-split-Cre, and KRT20-ERCreER knock-in human colon organoids via genome engineering. p27+ dormant cells were further visualized with the p27-mVenus reporter. To analyze the dynamics of human colonic stem cells in vivo, we orthotopically xenotransplanted fluorescence-labeled human colon organoids into immune-deficient mice. The cell cycle dynamics in xenograft cells were evaluated using 5-ethynyl-2′-deoxyuridine pulse-chase analysis. The clonogenic capacity of slow-cycling human stem cells or differentiated cells was analyzed in the context of homeostasis, LGR5 ablation, and 5-fluorouracil–induced mucosal injury. Results: Single-cell RNA sequencing analysis illuminated the presence of nondividing LGR5+ stem cells in the human colon. Visualization and lineage tracing of slow-cycling LGR5+p27+ cells and orthotopic xenotransplantation validated their homeostatic lineage-forming capability in vivo, which was augmented by 5-FU–induced mucosal damage. Transforming growth factor–β signaling regulated the quiescent state of LGR5+ cells. Despite the plasticity of differentiated KRT20+ cells, they did not display clonal growth after 5-FU–induced injury, suggesting that occupation of the niche environment by LGR5+p27+ cells prevented neighboring differentiated cells from de-differentiating. Conclusions: Our results highlight the quiescent nature of human LGR5+ colonic stem cells and their contribution to post-injury regeneration.

Background and aims: Endoscopic remission is known to be defined as a Mayo endoscopic subscore (MES) of ≤1 in patients with ulcerative colitis (UC). However, some individuals experience relapse even after showing endoscopic remission under white-light imaging (WLI), and no tool exists that can detect these individuals. The aim of this study was to clarify the usefulness of texture and color enhancement imaging (TXI) in the assessment of inflammation in patients with UC. Methods: This was a prospective, single-arm, observational study conducted at a university hospital. From January 2021 to December 2021, 146 UC patients with endoscopic remission were enrolled. Images were evaluated by WLI, TXI, and pathologic evaluation, followed by prognostic studies. The primary endpoint of the study was the cumulative relapse of UC in each TXI score. The secondary endpoints were the association between TXI and pathologic scores, predictors of relapse, and interobserver agreement between the MES and TXI scores. Results: Patients with TXI score 2 had significantly lower UC relapse-free rates than did those with TXI scores 0-1 (log-rank test, P < .01). When pathologic remission was defined as Matts grade ≤2, the rate of pathologic remission decreased significantly with higher TXI scores (P = .01). In multivariate analysis, TXI score 2 was the only risk factor for UC relapse (P < .01; hazard ratio, 4.16; 95% confidence interval, 1.72-10.04). Interobserver agreement on the TXI score was good (κ = 0.597-0.823). Conclusion: TXI can be used to identify populations with poor prognosis in MES 1, for whom treatment intensification has been controversial.