Possible Role of Image-Enhanced Endoscopy in the Evaluation of Mucosal Healing of Ulcerative Colitis.

BACKGROUND: Mucosal healing (MH) is recognized as a therapeutic target in ulcerative colitis (UC) because of evidence that it is associated with favorable clinical outcomes. Current endoscopic assessment of MH by conventional white-light endoscopy is subject to several important clinical issues including the subjective nature of assessment, intra- and interobserver variability, and persistent microscopic inflammation, even in mucosa it was observed as quiescent on conventional endoscopy. SUMMARY: Advances in image-enhancement technologies enable the provision of high-contrast images that emphasize the mucosal structures, blood vessel patterns, and color tones of the intestinal mucosa, and recently, several image-enhanced endoscopy (IEE) techniques have become available for the assessment of MH in UC. Narrow-band imaging and dual-red imaging facilitate visualization of mucosal vascular structures, which is useful for detecting minor inflammation and predicting relapse because of the capturing of information on incomplete vascular regeneration in patients with UC. Linked-color imaging (LCI) is optimized to emphasize the redness of the mucosa and blood vessels, and is superior for depicting subtle color changes arising from mucosal inflammation. LCI could possibly be used to stratify UC patients with MH on conventional endoscopy. Autofluorescence imaging and i-scan can also depict subtle histological changes underlying the healing of mucosa in UC, revealing them as simple color changes. KEY MESSAGES: Accumulating evidence suggests that IEE techniques could overcome current unmet needs in the endoscopic assessment of MH in UC and contribute to improving therapy based on treat-to-target strategies.

Early-Life Microbial Restitution Reduces Colitis Risk Promoted by Antibiotic-Induced Gut Dysbiosis in Interleukin 10-/- Mice.

BACKGROUND & AIMS: Perturbations in the early-life gut microbiome are associated with increased risk for complex immune disorders like inflammatory bowel diseases. We previously showed that maternal antibiotic-induced gut dysbiosis vertically transmitted to offspring increases experimental colitis risk in interleukin (IL) 10 gene deficient (IL10-/-) mice, a finding that may result from the loss/lack of essential microbes needed for appropriate immunologic education early in life. Here, we aimed to identify key microbes required for proper development of the early-life gut microbiome that decrease colitis risk in genetically susceptible animals. METHODS: Metagenomic sequencing followed by reconstruction of metagenome-assembled genomes was performed on fecal samples of IL10-/- mice with and without antibiotic-induced dysbiosis to identify potential missing microbial members needed for immunologic education. One high-value target strain was then engrafted early and/or late into the gut microbiomes of IL10-/- mice with antibiotic-induced dysbiosis. RESULTS: Early-, but not late-, life engraftment of a single dominant Bacteroides strain of non-antibiotic-treated IL10-/- mice was sufficient to restore the development of the gut microbiome, promote immune tolerance, and prevent colitis in IL10-/- mice that had antibiotic-induced dysbiosis. CONCLUSIONS: Restitution of a keystone microbial strain missing in the early-life antibiotic-induced gut dysbiosis results in recovery of the microbiome, proper development of immune tolerance, and reduced risk for colitis in genetically prone hosts.

Functional analysis of mutant SLCO2A1 transporters found in patients with chronic enteropathy associated with SLCO2A1.

BACKGROUND AND AIM: Chronic enteropathy associated with the solute carrier organic anion transporter family member 2A1 (SLCO2A1), or CEAS, causes anemia and hypoalbuminemia in young people. Dysfunction of the SLCO2A1 transporter protein is thought to involve genetic mutation, but mutant proteins have not been functionally characterized. We examined the prostaglandin E2 (PGE2 ) transport ability of recombinant SLCO2A1 proteins containing 11 SLCO2A1 mutations found in CEAS patients. METHODS: Wild-type and mutant SLCO2A1 proteins were forcibly expressed in Xenopus laevis oocytes, and measurements of PGE2 uptake and transport capacity were compared. The membrane protein topology and functionality of the eight SLCO2A1 mutations involving single-nucleotide substitutions were predicted using computer analysis. RESULTS: The extent of functional disruption of the 11 SLCO2A1 mutations identified in CEAS patients was variable, with 10 mutations (421GT, 547GA, 664GA, 770GA, 830dupT, 830delT, 940 + 1GA, 1372GT, 1647GT, and 1807CT) resulting in loss or reduction of PGE2 transport, excluding 97GC. CONCLUSION: PGE2 transport ability of recombinant SLCO2A1 in X. laevis oocytes was hindered in 10/11 SLCO2A1 mutations identified in patients with CEAS. Further studies on the relationships between the different mutations and PGE2 transport and clinical features, such as severity, are needed.

A consensus statement on health-care transition for childhood-onset inflammatory bowel disease patients.

Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder of the intestine. The incidence of IBD is increasing worldwide, including Japan, and in approximately 25% of all affected patients it is diagnosed before 18 years of age. For the health maintenance of such patients, planned transition to adult care systems is essential. Previous Japanese surveys have revealed gaps between adult and pediatric gastroenterologists with regard to their knowledge and perception of health-care transition for patients with childhood-onset IBD. In 2021-2022, several Web workshops to discuss issues related to the transitional care of IBD patients were held by the Ministry of Health, Labour and Welfare of Japan as part of their program for research on intractable diseases. Clinicians experienced in IBD treatment for pediatric and adult patients participated. As a result, this panel of adult and pediatric gastroenterologists developed five consensus statements on the issue of "transfer from pediatric to adult care" and nine statements on the issue of "addressing transitional care (transition program)." To address current gaps in health-care transition for childhood-onset IBD patients, a programmed approach to transition, and better partnerships between pediatric and adult gastroenterologists are indicated. It is hoped that this consensus statement will provide a basis for the development of appropriate guidelines for clinical practice.

Effectiveness of introducing a 20-gauge core biopsy needle with a core trap in EUS-FNA/B for diagnosing pancreatic cancer.

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/B) is a standard method for pathological diagnosis of pancreatic solid lesions. The EchoTip ProCore 20G® (PC20), a 20-gauge biopsy needle with a forward-bevel core trap, has been available in Japan since 2015. METHODS: We compared the efficacy of the PC20 with that of the EchoTip ProCore 22G® (PC22) and Acquire 22G® (AC22) in EUS-FNA/B for diagnosing pancreatic cancer. This retrospective study included 191 patients with pancreatic cancer who underwent EUS-FNA/B using the PC20, PC22, or AC22 at our facility from April 2013 to October 2019. We investigated the patients' clinical characteristics and the diagnostic accuracy and safety of each needle. RESULTS: A sufficient stroke length of puncture was secured in all patients. The maximum length under EUS was shorter with the AC22 (22.1 ± 2.2 mm) than PC20 (30.6 ± 0.7 mm, p < 0.01) and PC22 (30.3 ± 0.8 mm, p < 0.01). The histological accuracy was 96.4% with the PC20 but only 58.8% with the PC22 (adjusted p (p-adj) < 0.0001) and 75.0% with the AC22 (p-adj = 0.06). The diagnostic accuracy of the combination of histology and cytology was 96.4% with the PC20, while it was 72.1% with the PC22 (p-adj < 0.0001) and 91.7% with the AC22 (p-adj > 0.99). One patient (0.9%) in the PC20 group developed mild pancreatitis, but no adverse events occurred with the other needles. CONCLUSIONS: The PC20 showed better diagnostic capability than the PC22. The diagnostic efficacy was similar between the PC20 and AC22. The high histological accuracy of the PC20 could be advantageous for lesions in which histological assessment is critical.

Extent of disease affects the usefulness of fecal biomarkers in ulcerative colitis.

BACKGROUND: Fecal biomarkers are considered to be useful surrogate markers for endoscopic activity. Given the mechanisms of fecal biomarkers, we hypothesized that the extent of ulcerative colitis (UC; pancolitis, left-sided colitis, and proctitis) could affect the usefulness of fecal biomarkers for assessing endoscopic and clinical disease activity; however, few studies have evaluated the utility of fecal biomarkers in the disease extent of UC. METHODS: Fecal calprotectin, a fecal immunochemical test for hemoglobin, and fecal lactoferrin were used as fecal biomarkers. UC patients, who underwent colonoscopy within 30 days of the fecal biomarker test, participated in this observational study. Clinical and endoscopic disease activity was assessed using the Lichtiger Index and Mayo endoscopic subscore (MES), respectively. RESULTS: A total of 162 colonoscopies were performed on 133 UC patients. A correlation analysis between each biomarker and the MES for each disease-extent subgroup showed a decreased correlation in the proctitis compared with the other groups. With the exception of proctitis, it was possible to distinguish between MES 0 and MES ≥ 1 with high area-under-the-curve values for fecal calprotectin and fecal lactoferrin. The fecal immunochemical test for hemoglobin was superior at discriminating MES 0 for proctitis. CONCLUSIONS: For the practical application of fecal biomarkers for UC patients, it is necessary to consider disease extent before use. In particular, patients with proctitis exhibit a low correlation between stool biomarkers and endoscopic findings. The usefulness of these biomarkers for endoscopic remission is reduced, except for the fecal immunochemical test for hemoglobin.

Gastropathy associated with lanthanum phosphate deposition that was endoscopically tracked for 3 years. A case report.

BACKGROUND: With the recent increased use of lanthanum carbonate, several cases of lanthanum phosphate deposition to gastric mucosa in dialysis patients have been reported. However, the endoscopic appearance of the early-stage lesion and the over-time alterations of endoscopic findings due to the progression of lanthanum phosphate deposition remain unclear. CASE PRESENTATION: An 80-year-old man receiving dialysis and taking lanthanum carbonate as a phosphate binder over a 4-year period underwent upper gastrointestinal endoscopy four times beginning 1 year after initiation of treatment. The first endoscopic examination (after 1 year of exposure to lanthanum carbonate) revealed rough mucosa with a few areas of white granular mucosa. Over the 3 years of endoscopic follow-up, the white granular mucosa spread and multiple erosions appeared. Histopathological findings of biopsy specimens from an erosion showed extensive infiltration by histiocytes containing deposits. Scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX) revealed that the presence of the deposits containing phosphorus and lanthanum in the gastric mucosa. On the basis of these results, the patient was diagnosed with gastropathy associated with lanthanum phosphate deposition. CONCLUSIONS: Over a 3-year period, endoscopic findings associated with lanthanum deposition gradually changed and expanded from the early stage.

Endoscopic severe mucosal atrophy indicates the presence of gastric cancer after Helicobacter pylori eradication -analysis based on the Kyoto classification.

BACKGROUND: Gastric cancer after Helicobacter pylori (HP) eradication is a crucial clinical challenge today as HP eradication therapy is widely performed. Detecting gastric cancer after HP eradication tends to be difficult with normal white-light endoscopy. In the present study, we aimed to identify easily-evaluated endoscopic findings that indicate the presence of gastric cancer after HP eradication so that endoscopists can consider additional detailed examinations at the site. METHODS: We analyzed the endoscopic images of 43 patients who underwent endoscopic submucosal dissection for early gastric cancer after HP eradication and 119 patients with an HP eradication history who underwent esophagogastroduodenoscopy for a medical checkup. Endoscopic findings were evaluated according to the Kyoto classification of gastritis (atrophy, intestinal metaplasia, enlarged folds, nodularity, and diffuse redness) and map-like redness. RESULTS: Patients with gastric cancer had significantly higher total Kyoto risk scores; more atrophy, intestinal metaplasia, and diffuse redness; and a significantly higher prevalence of map-like redness compared with those without gastric cancer, in the univariate analyses. We used logistic regression analysis with forward selection based on the likelihood ratio to develop a model using atrophy and diffuse redness. Receiver operating characteristic analysis showed that a score of A2 in the Kyoto classification of gastritis (open-type atrophic pattern in the Kimura-Takemoto classification) was an endoscopic marker for the presence of post-HP-eradication gastric cancer. CONCLUSIONS: Endoscopic severe gastric mucosal atrophy is useful to screen patients for gastric cancer after HP eradication.

Nectins and nectin-like molecules: roles in contact inhibition of cell movement and proliferation.

Nectins and nectin-like molecules (Necls) are immunoglobulin-like transmembrane cell adhesion molecules that are expressed in various cell types. Homophilic and heterophilic engagements between family members provide cells with molecular tools for intercellular communications. Nectins primarily regulate cell-cell adhesions, whereas Necls are involved in a greater variety of cellular functions. Recent studies have revealed that nectins and NECL-5, in cooperation with integrin alphavbeta3 and platelet-derived growth factor receptor, are crucial for the mechanisms that underlie contact inhibition of cell movement and proliferation; this has important implications for the development and tissue regeneration of multicellular organisms and the phenotypes of cancer cells.

Elevated fecal calprotectin and lactoferrin associated with small intestinal lesions in patients with Behçet disease.

BACKGROUND AND AIMS: Small intestinal lesions in patients with Behçet disease (BD) have a risk of perforation and hemorrhage requiring surgery. However, no screening strategy for such lesions has been established. We investigated small intestinal lesions in BD patients with video capsule endoscopy (VCE) and analyzed clinical characteristics to identify noninvasive biomarkers of such lesions. METHODS: This study included 33 BD patients who underwent VCE (PillCam® SB3) at our institution from June 2016 to January 2019. Clinical characteristics, including age, sex, disease duration, body mass index, gastrointestinal symptoms, eye involvement, and blood examinations, were obtained from the medical records of 27 of the 33 patients. Fecal immunochemical tests for hemoglobin, fecal calprotectin (FC), and fecal lactoferrin (FL) were measured. VCE findings of 145 healthy Japanese individuals from a previous report were used as controls. RESULTS: Two intestinal BD patients were included in the 27 patients. We observed that BD patients exhibit more small intestinal lesions compared with healthy individuals, including erosions, ulcers, and total lesions (erosions or ulcers). FC and FL levels were significantly higher in patients with versus without small intestinal lesions (P = 0.034 and P = 0.046, respectively). Receiver operating characteristic analyses demonstrated that FC (cutoff value = 119 µg/g) and FL (cutoff value = 17 µg/g) were biomarkers for small intestinal lesions in patients with BD. CONCLUSION: The present study using VCE showed that patients with BD had more small intestinal lesions than healthy individuals. FC and FL could be useful for screening BD patients who may have small intestinal lesions.

MEFV Gene-Related Enterocolitis Account for Some Cases Diagnosed as Inflammatory Bowel Disease Unclassified.

BACKGROUND AND AIMS: Familial mediterranean fever (FMF), an autoinflammatory disease, is characterized by periodic fever and serositis. An MEFV gene mutation has been identified as the cause of FMF. Recently, patients with MEFV gene mutations and chronic gastrointestinal mucosal inflammation mimicking inflammatory bowel disease (IBD) have been reported. In this retrospective study, we analyzed the clinical characteristics of patients with IBD unclassified (IBDU) with MEFV gene mutations. METHODS: MEFV gene analysis was performed on 8 patients with IBDU among 710 patients with IBD who had been treated at Kyorin University Hospital from April 2016 to December 2018. Clinical manifestations, endoscopic findings, and serological markers were also analyzed. RESULTS: The average of the 8 patients with IBDU (3 men, 5 women) was 32.7 ± 6.4 years (range 26-76 years). Their symptoms comprised diarrhea (n = 8, 100%), hematochezia (n = 3, 37.5%), abdominal pain (n = 3, 37.5%), high fever (n = 2, 16.5%), and other periodic symptoms (n = 2, 16.5%). MEFV gene mutation was confirmed in 4/8 of these patients. Colonoscopy showed various mucosal lesions, rectal sparing, right side dominant colitis, pseudopolyposis, and granular protrusions. Colchicine was administered to 5 of the 8 patients (4 with and 1 without MEFV mutation) who were resistant to conventional treatment for ulcerative colitis. Clinical and endoscopic improvement was observed in all of 5 patients treated with colchicine. CONCLUSIONS: Some patients diagnosed as having IBDU have enterocolitis related to MEFV gene mutation and respond to colchicine therapy.

Daikenchuto (TU-100) Suppresses Tumor Development in the Azoxymethane and APCmin/+ Mouse Models of Experimental Colon Cancer.

Chemopreventative properties of traditional medicines and underlying mechanisms of action are incompletely investigated. This study demonstrates that dietary daikenchuto (TU-100), comprised of ginger, ginseng, and Japanese pepper effectively suppresses intestinal tumor development and progression in the azoxymethane (AOM) and APCmin/+ mouse models. For the AOM model, TU-100 was provided after the first of six biweekly AOM injections. Mice were sacrificed at 30 weeks. APCmin/+ mice were fed diet without or with TU-100 starting at 6 weeks, and sacrificed at 24 weeks. In both models, dietary TU-100 decreased tumor size. In APC min/+ mice, the number of small intestinal tumors was significantly decreased. In the AOM model, both TU-100 and Japanese ginseng decreased colon tumor numbers. Decreased Ki-67 and ß-catenin immunostaining and activation of numerous transduction pathways involved in tumor initiation and progression were observed. EGF receptor expression and stimulation/phosphorylation in vitro were investigated in C2BBe1 cells. TU-100, ginger, and 6-gingerol suppressed EGF receptor induced Akt activation. TU-100 and ginseng and to a lesser extent ginger or 6-gingerol inhibited EGF ERK1/2 activation. TU-100 and some of its components and metabolites of these components inhibit tumor progression in two mouse models of colon cancer by blocking downstream pathways of EGF receptor activation. Copyright © 2016 John Wiley & Sons, Ltd.

Necl-5/poliovirus receptor interacts with VEGFR2 and regulates VEGF-induced angiogenesis.

RATIONALE: Vascular endothelial growth factor (VEGF), a major proangiogenic agent, exerts its proangiogenic action by binding to VEGF receptor 2 (VEGFR2), the activity of which is regulated by direct interactions with other cell surface proteins, including integrin α(V)ß(3). However, how the interaction between VEGFR2 and integrin α(V)ß(3) is regulated is not clear. OBJECTIVE: To investigate whether Necl-5/poliovirus receptor, an immunoglobulin-like molecule that is known to bind integrin α(V)ß(3), regulates the interaction between VEGFR2 and integrin α(V)ß(3), and to clarify the role of Necl-5 in the VEGF-induced angiogenesis. METHODS AND RESULTS: Necl-5-knockout mice displayed no obvious defect in vascular development; however, recovery of blood flow after hindlimb ischemia and the VEGF-induced neovascularization in implanted Matrigel plugs were impaired in Necl-5-knockout mice. To clarify the mechanism of the regulation of angiogenesis by Necl-5, we investigated the roles of Necl-5 in the VEGF-induced angiogenic responses in vitro. Knockdown of Necl-5 by siRNAs in human umbilical vein endothelial cells (HUVECs) inhibited the VEGF-induced capillary-like network formation on Matrigel, migration, and proliferation, and conversely, enhanced apoptosis. Coimmunoprecipitation assays showed the interaction of Necl-5 with VEGFR2, and knockdown of Necl-5 prevented the VEGF-induced interaction of integrin α(V)ß(3) with VEGFR2. Knockdown of Necl-5 suppressed the VEGFR2-mediated activation of downstream proangiogenic and survival signals, including Rap1, Akt, and endothelial nitric oxide synthase. CONCLUSIONS: These results demonstrate the critical role of Necl-5 in angiogenesis and suggest that Necl-5 may regulate the VEGF-induced angiogenesis by controlling the interaction of VEGFR2 with integrin α(v)ß(3), and the VEGFR2-mediated Rap1-Akt signaling pathway.

Early intervention with adalimumab may contribute to favorable clinical efficacy in patients with Crohn's disease.

BACKGROUND: We evaluated the clinical efficacy of adalimumab (ADA) for Crohn's disease (CD) and analyzed predictive factors for clinical remission and long-term prognosis. METHODS: We retrospectively reviewed the medical records of 45 patients treated with ADA for CD at Keio University Hospital between October 2010 and March 2014. Clinical remission was defined as a Harvey-Bradshaw index of ≤4. RESULTS: Twenty-eight of 45 patients (62.2%) achieved clinical remission at week 4. Among these 28 patients, 18 patients (64.3%) maintained clinical remission at week 26, and among these, 16 patients (88.9%) maintained clinical remission at week 52. Absence of a history of bowel resection and absence of prior anti-tumor necrosis factor (anti-TNF) therapy were significant predictive factors for clinical remission at week 4 upon multivariate logistic regression analyses. Younger age and a disease duration of ≤3 years correlated with clinical remission at week 26 upon univariate analyses. Patients without a history of bowel resection showed significantly better long-term prognosis than those with a history of bowel resection (p = 0.01). None of the patients contracted a serious infectious disease. CONCLUSIONS: Younger age, shorter duration of disease, being naive to anti-TNF antagonists, and absence of a history of bowel resection were associated with the efficacy of ADA in CD patients.

Risk and management of intra-abdominal abscess in Crohn's disease treated with infliximab.

BACKGROUND AND AIMS: Infliximab (IFX) is a monoclonal antibody used to treat patients with Crohn's disease (CD). Intra-abdominal abscess formation is a major complication of CD with negative effects on patient prognosis. We have analyzed risk factors for abscess formation in CD patients treated with IFX. METHODS: CD patients who received IFX between January 2000 and April 2011 at Keio University Hospital were analyzed retrospectively. Risk factors for abscess formation were assessed by univariate and multivariate logistic regression analyses. RESULTS: Intra-abdominal abscess was seen in 15 of 258 patients. Univariate analyses showed serum C-reactive protein (CRP) concentration at 14 weeks after initiation of IFX (p = 0.021), serum albumin concentration at week 0 (p = 0.022) and week 14 (p = 0.004), the presence of anal lesions (p = 0.036), progression of intestine deformation (p = 0.015) and early loss of response to IFX (p < 0.0001) to be risk factors. Multivariate analysis showed that CRP concentration at 14 weeks [odds ratio (OR) 1.361] and loss of IFX response within 6 months (OR 5.361) were independent risk factors. CONCLUSIONS: Abscess formation should be suspected in patients with symptoms of CD recurrence during IFX therapy. Uncontrolled CRP concentration and early loss of response to IFX are risk factors.

Mucosal CXCR4+ IgG plasma cells contribute to the pathogenesis of human ulcerative colitis through FcγR-mediated CD14 macrophage activation.

BACKGROUND: Chronic inflammation characterised by IgG-producing plasma cell infiltration of colonic mucosa is a histological hallmark of ulcerative colitis (UC); however, whether its function is pathogenic or protective remains unclear. OBJECTIVE: To explore the contribution of intestinal IgG plasma cells to UC pathogenesis. METHODS: We isolated lamina propria mononuclear cells (LPMCs) from intestinal mucosa of UC patients and analysed the characteristics of intestinal plasma cells (expression profiles of differentiation molecules and chemokine receptors). We investigated the involvement of IgG-immune complex (IC)-Fc gamma receptor (FcγR) signalling in intestinal inflammation by examining the cytokine production by LPMCs in response to IgG-IC stimulation. RESULTS: IgG plasma cells that were markedly increased in number in the inflamed mucosa of UC patients showed a distinct expression profile (CD19(+)CD27(low), CCR10(low)CXCR4(high)) compared with IgA plasma cells (CD19(+/-)CD27(high), CCR10(high)CXCR4(-/low)). In vitro IgG-IC stimulation activated intestinal CD14 macrophages that were increased in number in the inflamed mucosa of UC patients via FcγRI and FcγRII, and induced the extensive production of pro-inflammatory cytokines such as tumour necrosis factor (TNF) and interleukin-1ß (IL-1ß), comparable to the effect of commensal bacteria stimulation. Co-stimulation with IgG-IC and commensal bacteria increased TNF and IL-1ß production more than stimulation with the latter alone. Furthermore, IgG-IC notably up-regulated the expression of TL1A, whereas commensal bacteria specifically induced IL-23. CONCLUSIONS: Collectively, these results demonstrate a novel aspect of UC pathogenesis in which unique IgG plasma cells infiltrate the inflamed mucosa via CXCR4, and critically influence UC pathogenesis by exacerbating mucosal inflammation through the activation of 'pathogenic' intestinal CD14 macrophages via IgG-IC-FcγR signalling.

Machine learning using clinical data at baseline predicts the medium-term efficacy of ustekinumab in patients with ulcerative colitis.

Predicting the therapeutic response to biologics before administration is a key clinical challenge in ulcerative colitis (UC). We previously reported a model for predicting the efficacy of vedolizumab (VDZ) for UC using a machine-learning approach. Ustekinumab (UST) is now available for treating UC, but no model for predicting its efficacy has been developed. When applied to patients with UC treated with UST, our VDZ prediction model showed positive predictive value (PPV) of 56.3% and negative predictive value (NPV) of 62.5%. Given this limited predictive ability, we aimed to develop a UST-specific prediction model with clinical features at baseline including background factors, clinical and endoscopic activity, and blood test results, as we did for the VDZ prediction model. The top 10 features (Alb, monocytes, height, MCV, TP, Lichtiger index, white blood cell count, MCHC, partial Mayo score, and CRP) associated with steroid-free clinical remission at 6 months after starting UST were selected using random forest. The predictive ability of a model using these predictors was evaluated by fivefold cross-validation. Validation of the prediction model with an external cohort showed PPV of 68.8% and NPV of 71.4%. Our study suggested the importance of establishing a drug-specific prediction model.