Safety and effectiveness of tofacitinib in Korean adult patients with ulcerative colitis: post-marketing surveillance study.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We aimed to identify the safety and effectiveness of tofacitinib in patients with UC in routine clinical settings in Korea. METHODS: This open-label, observational, prospective, post-marketing surveillance study was conducted at 22 hospitals in the Republic of Korea. Patients with moderate to severe active UC who received tofacitinib were included and followed up for up to 52 weeks. Tofacitinib was administered at a dosage of 10 mg twice daily for at least 8 weeks, followed by 5 or 10 mg twice daily at the investigator's discretion based on clinical evaluation according to the approved Korean label. Safety including adverse events (AEs) and effectiveness including clinical remission, clinical response, and endoscopic mucosal healing were evaluated. Safety analysis set was defined as all patients registered for this study who received at least one dose of tofacitinib according to the approved Korean label and followed up for safety data. Effectiveness analysis set included patients in the safety analysis set who were evaluated for overall effectiveness assessment and excluded patients who had received tofacitinib less than 8 weeks. RESULTS: A total of 110 patients were enrolled, of whom 106 patients were included in the safety population. The median duration of treatment was 370 days and the treatment duration ranged from 16 to 684 days for the safety population. AEs occurred in 42 patients (39.6%). Serious AEs (SAEs) occurred in 7 patients (6.6%) and of them, there were 2 cases of serious infections. These serious infections were reported as Adverse Event of Special Interest (AESI) in this study and no other AESI were reported. There were no cases of death during the study period. Clinical remission rates were 40.0%, 46.7%, 57.6%, and 55.1% at 8, 16, 24, and 52 weeks, and clinical response rates were 77.8%, 87.9%, 56.6%, and 81.4% at each visit, respectively. Endoscopic mucosal healing rates were 58.7% at 16 weeks and 46.2% at 52 weeks. CONCLUSION: Tofacitinib was effective in Korean patients with moderate to severe active UC and the safety findings were consistent with the known safety profile of tofacitinib. This study confirmed the safety and effectiveness of tofacitinib in Korean patients with moderate to severe active UC in routine clinical settings. TRIAL REGISTRATION: This study is registered in the ClinicalTrials.gov under the identifier NCT04071405, registered on 28 August 2019.

Diagnosis of Crohn's disease and ulcerative colitis using the microbiome.

BACKGROUND: Inflammatory bowel disease (IBD) is a multifactorial chronic inflammatory disease resulting from dysregulation of the mucosal immune response and gut microbiota. Crohn's disease (CD) and ulcerative colitis (UC) are difficult to distinguish, and differential diagnosis is essential for establishing a long-term treatment plan for patients. Furthermore, the abundance of mucosal bacteria is associated with the severity of the disease. This study aimed to differentiate and diagnose these two diseases using the microbiome and identify specific biomarkers associated with disease activity. RESULTS: Differences in the abundance and composition of the microbiome between IBD patients and healthy controls (HC) were observed. Compared to HC, the diversity of the gut microbiome in patients with IBD decreased; the diversity of the gut microbiome in patients with CD was significantly lower. Sixty-eight microbiota members (28 for CD and 40 for UC) associated with these diseases were identified. Additionally, as the disease progressed through different stages, the diversity of the bacteria decreased. The abundances of Alistipes shahii and Pseudodesulfovibrio aespoeensis were negatively correlated with the severity of CD, whereas the abundance of Polynucleobacter wianus was positively correlated. The severity of UC was negatively correlated with the abundance of A. shahii, Porphyromonas asaccharolytica and Akkermansia muciniphilla, while it was positively correlated with the abundance of Pantoea candidatus pantoea carbekii. A regularized logistic regression model was used for the differential diagnosis of the two diseases. The area under the curve (AUC) was used to examine the performance of the model. The model discriminated UC and CD at an AUC of 0.873 (train set), 0.778 (test set), and 0.633 (validation set) and an area under the precision-recall curve (PRAUC) of 0.888 (train set), 0.806 (test set), and 0.474 (validation set). CONCLUSIONS: Based on fecal whole-metagenome shotgun (WMS) sequencing, CD and UC were diagnosed using a machine-learning predictive model. Microbiome biomarkers associated with disease activity (UC and CD) are also proposed.

Enrichment of Activated Fibroblasts as a Potential Biomarker for a Non-Durable Response to Anti-Tumor Necrosis Factor Therapy in Patients with Crohn's Disease.

We investigated whether the response to anti-tumor necrosis factor (anti-TNF) treatment varied according to inflammatory tissue characteristics in Crohn's disease (CD). Bulk RNA sequencing (RNA-seq) data were obtained from inflamed and non-inflamed tissues from 170 patients with CD. The samples were clustered based on gene expression profiles using principal coordinate analysis (PCA). Cellular heterogeneity was inferred using CiberSortx, with bulk RNA-seq data. The PCA results displayed two clusters of CD-inflamed samples: one close to (Inflamed_1) and the other far away (Inflamed_2) from the non-inflamed samples. Inflamed_1 was rich in anti-TNF durable responders (DRs), and Inflamed_2 was enriched in non-durable responders (NDRs). The CiberSortx results showed that the cell fraction of activated fibroblasts was six times higher in Inflamed_2 than in Inflamed_1. Validation with public gene expression datasets (GSE16879) revealed that the activated fibroblasts were enriched in NDRs over Next, we used DRs by 1.9 times pre-treatment and 7.5 times after treatment. Fibroblast activation protein (FAP) was overexpressed in the Inflamed_2 and was also overexpressed in the NDRs in both the RISK and GSE16879 datasets. The activation of fibroblasts may play a role in resistance to anti-TNF therapy. Characterizing fibroblasts in inflamed tissues at diagnosis may help to identify patients who are likely to respond to anti-TNF therapy.

Improving the tolerability and safety of 1-L polyethylene glycol plus low-dose ascorbic acid for bowel preparation in a healthy population: a randomized multicenter clinical trial.

BACKGROUND AND AIMS: One-liter polyethylene glycol plus ascorbic acid (PEG-ASC) improves patient tolerability, but some patients still show low tolerability to a relatively high content of ASC. This study aimed to improve the tolerability and safety of 1-L PEG with low-dose ASC in comparison with standard 1-L and 2-L PEG-ASC. METHODS: This was a randomized, controlled, double-blinded, multicenter, noninferiority trial involving 215 healthy adults who underwent colonoscopy from June 2020 to January 2021. Efficacy, tolerability, and safety were compared among 1-L PEG with low-dose ASC (50% lower ASC concentration in group A and 25% lower ASC concentration in groups B and C) and standard 1-L and 2-L PEG-ASC with all split regimens. RESULTS: One-liter PEG with low-dose ASC (groups A-C) had similar bowel cleansing efficacies according to the Harefield Cleansing Scale and Boston Bowel Preparation Scale, without negative clinical performance, compared with standard 1-L and 2-L PEG-ASC preparation (all P > .1). One-liter PEG with low-dose ASC had better tolerability compared with 2-L PEG-ASC and less residual fluid retention in the stomach compared with 1-L PEG-ASC, proportional to the amount of ASC. No significant differences were found in the incidences of overall adverse events, mild adverse events, or death or in the occurrence of gastroduodenal erosion or ulcer in upper endoscopy. CONCLUSIONS: One-liter PEG with low-dose ASC (25%-50% reduction in dose) for bowel cleansing showed similar efficacy and safety compared with standard 1-L or 2-L PEG-ASC, better tolerability compared with 2-L PEG-ASC, and less residual gastric fluid retention compared with standard 1-L PEG-ASC. (Clinical trial registration number: KCT0005490.).

Second Victim Experience and Perception Discordance of the Colonoscopic Perforation.

BACKGROUND: Perforation is the most serious adverse event of colonoscopy, but rarely considered from the view of colonoscopists' second victim experience and perception discordance between colonoscopists and patients. AIMS: We aimed to evaluate colonoscopists' second victim experience and the perception discordance between colonoscopists and patients for the colonoscopic perforation. METHODS: A survey for colonoscopic perforation was performed for the colonoscopists and outpatients who visited the university hospital between February 1, 2020, and April 30, 2020. The questionnaire included questions regarding colonoscopists' satisfaction for the intervention strategies offered to patients and patient-colonoscopist perception on colonoscopic perforation. A modified Korean version of the "Second Victim Experience and Support Tool (K-SVEST)" was used to assess the second victim experiences and supportive resources for the colonoscopists. RESULTS: Survey results from 160 colonoscopists and 165 patients were analyzed. The colonoscopists' satisfaction scores were higher for strategies related to sufficient explanation, empathy, courteous listening, and monetary compensation. The scores of the K-SVEST for the second victim experience were highest in psychological distress, followed by loss of professional self-efficacy, colleague support, physical distress, non-work-related support, institutional support, and turnover intentions/absenteeism. Significant patient-colonoscopist discordance was noted for the same colonoscopic perforation scenario on the judgment of medical error, health professionals' apology, monetary compensation, and criminal penalties for the colonoscopists. CONCLUSIONS: Colonoscopists can suffer emotionally and physically from the second victim experience after colonoscopic perforation. In addition, the significant patient-colonoscopist discordance should be considered to make a better communication for the colonoscopic perforation.

Comparison of 1-Year Colectomy Risk Between the US and Korean Patients with Acute Severe Ulcerative Colitis: A Propensity Score Matching Analysis.

BACKGROUND: Colectomy risk after acute severe ulcerative colitis (ASUC) has not been compared between Eastern and Western countries. We compared the 1-year colectomy risk after ASUC between Korea and the USA. METHODS: Data on patients admitted for ASUC to five tertiary referral hospitals in Korea and Mount Sinai Hospital, New York, the USA, between January 2015 and January 2019 were reviewed retrospectively. For comparability between groups, a 1:1 propensity score matching (PSM) was performed. The primary outcome was colectomy, and secondary outcomes were mortality, readmission, and venous thromboembolism (VTE) within 1-year of the index admission for ASUC. The risk of each outcome was compared using Cox proportional hazards model in pre-matched cohort and Kaplan-Meier analysis with log-rank test in post-matched cohort. RESULTS: 290 ASUC patients were included in the study (121 Korea, 169 the USA). After PSM, 56 patients were selected in each group with no significant differences in baseline variables. At 1 year after ASUC, colectomy was less common in Korea than in the USA [3 (5.4%) vs. 24 (42.9%), p < 0.001]. The cumulative colectomy risk was significantly higher in the USA than in Korea in pre-matched cohort [adjusted hazard ratio 7.89, 95% confidence interval 3.23 to 19.22] and in post-matched cohort (log-rank p < 0.001), while there was no difference in cumulative risk of mortality, readmission, and VTE. CONCLUSION: Colectomy risk within 1 year of ASUC is significantly higher in the USA than in Korea. We observed no differences in mortality, readmission, and VTE between the two groups.

Nationwide validation study of diagnostic algorithms for inflammatory bowel disease in Korean National Health Insurance Service database.

BACKGROUND AND AIM: We conducted a nationwide validation study of diagnostic algorithms to identify cases of inflammatory bowel disease (IBD) within the Korea National Health Insurance System (NHIS) database. METHOD: Using the NHIS dataset, we developed 44 algorithms combining the International Classification of Diseases (ICD)-10 codes, codes for Rare and Intractable Diseases (RID) registration and claims data for health care encounters, and pharmaceutical prescriptions for IBD-specific drugs. For each algorithm, we compared the case identification results from electronic medical records data with the gold standard (chart-based diagnosis). A multiple sampling test verified the validation results from the entire study population. RESULTS: A random nationwide sample of 1697 patients (848 potential cases and 849 negative control cases) from 17 hospitals were included for validation. A combination of the ICD-10 code, ≥ 1 claims for health care encounters, and ≥ 1 prescription claims (reference algorithm) achieved excellent performance (sensitivity, 93.1% [95% confidence interval 91-94.7]; specificity, 98.1% [96.9-98.8]; positive predictive value, 97.5% [96.1-98.5]; negative predictive value, 94.5% [92.8-95.8]) with the lowest error rate (4.2% [3.3-5.3]). The multiple sampling test confirmed that the reference algorithm achieves the best performance regarding IBD diagnosis. Algorithms including the RID registration codes exhibited poorer performance compared with that of the reference algorithm, particularly for the diagnosis of patients affiliated with secondary hospitals. The performance of the reference algorithm showed no statistical difference depending on the hospital volume or IBD type, with P-value < 0.05. CONCLUSIONS: We strongly recommend the reference algorithm as a uniform standard operational definition for future studies using the NHIS database.

Predictive Factors for Differentiating Between Crohn's Disease and Intestinal Tuberculosis in Koreans.

OBJECTIVES: A differential diagnosis between intestinal tuberculosis (ITB) and Crohn's disease (CD) is challenging. The aim of this study was to investigate the clinical, endoscopic, and histological features and to create a predictive score model for differentiating CD and ITB. METHODS: In total, 261 patients, 99 with ITB and 162 with CD, were recruited from seven tertiary centers from 2005 to 2013 and reviewed retrospectively. For the creation of a validated model, parameters were selected by univariate logistic regression and receiver operating characteristic curve analyses. Then, the prediction model was established on the basis of ß-coefficients of the multivariate logistic regression. For the validation of the model, the same regression equation was tested on the other group. RESULTS: Age, diarrhea, ring-shaped ulcer, longitudinal ulcer, sigmoid involvement, suspicious radiological pulmonary tuberculosis, and gender were selected as the factors for a seven-marker model. In the seven-marker model of the validation data set, the sensitivity, specificity, positive predictive value, and negative predictive value with a cutoff level of 0.35 were 98.0, 92.4, 88.9, and 98.6, respectively. CONCLUSIONS: The seven-marker model seems to be highly reliable for differentiating between ITB and CD and could be conveniently used by clinicians to obtain results.

Regulatory Variants on the Leukocyte Immunoglobulin-Like Receptor Gene Cluster are Associated with Crohn's Disease and Interact with Regulatory Variants for TAP2.

BACKGROUND AND AIMS: Crohn's disease [CD] has a complex polygenic aetiology with high heritability. There is ongoing effort to identify novel variants associated with susceptibility to CD through a genome-wide association study [GWAS] in large Korean populations. METHODS: Genome-wide variant data from 902 Korean patients with CD and 72 179 controls were used to assess the genetic associations in a meta-analysis with previous Korean GWAS results from 1621 patients with CD and 4419 controls. Epistatic interactions between CD-risk variants of interest were tested using a multivariate logistic regression model with an interaction term. RESULTS: We identified two novel genetic associations with the risk of CD near ZBTB38 and within the leukocyte immunoglobulin-like receptor [LILR] gene cluster [p < 5 × 10-8], with highly consistent effect sizes between the two independent Korean cohorts. CD-risk variants in the LILR locus are known quantitative trait loci [QTL] for multiple LILR genes, of which LILRB2 directly interacts with various ligands including MHC class I molecules. The LILR lead variant exhibited a significant epistatic interaction with CD-associated regulatory variants for TAP2 involved in the antigen presentation of MHC class I molecules [p = 4.11 × 10-4], showing higher CD-risk effects of the TAP2 variant in individuals carrying more risk alleles of the LILR lead variant (odds ratio [OR] = 0.941, p = 0.686 in non-carriers; OR = 1.45, p = 2.51 × 10-4 in single-copy carriers; OR = 2.38, p = 2.76 × 10-6 in two-copy carriers). CONCLUSIONS: This study demonstrated that genetic variants at two novel susceptibility loci and the epistatic interaction between variants in LILR and TAP2 loci confer a risk of CD.

Effects of COVID-19 vaccines on patient-reported outcomes in patients with inflammatory bowel disease: a multicenter survey study in Korea.

BACKGROUND/AIMS: The impact of vaccination on inflammatory bowel disease (IBD) patients is still unknown, and no studies have assessed the changes in patient-reported outcomes (PROs) after vaccination in patients with IBD. Therefore, in this study, we investigated the impact of vaccines on the PROs of patients with IBD. METHODS: We conducted a questionnaire survey of patients with IBD who visited outpatient clinics at 4 specialized IBD clinics of referral university hospitals from April 2022 to June 2022. A total of 309 IBD patients were included in the study. Patient information was collected from a questionnaire and their medical records, including laboratory findings, were reviewed retrospectively. Risk factors associated with an increase in PROs after COVID-19 vaccination were analyzed using logistic regression analyses. In addition, we assessed whether there were differences in variables by vaccine order using the linear mixed model. RESULTS: In multivariate analysis, young age ( < 40 years) and ulcerative colitis (UC) were found to be independent risk factors for aggravation of PROs in patients with IBD. In all patients, platelet count significantly increased with continued vaccination in multiple pairwise comparisons. In UC patients, PROs such as the short health scale, UC-abdominal signs and symptoms, and UC-bowel signs and symptoms were aggravated significantly with continued vaccination. There was no significant increase in the variables of patients with Crohn's disease. CONCLUSIONS: Therefore, there may be a need to counsel patients with IBD younger than 40 years of age, and patients with UC before they receive COVID-19 vaccinations.

Akt and Cks1 are related with lymph node metastasis in gastric adenocarcinoma.

BACKGROUND/AIMS: There is increasing evidence that the PI3K/Akt signal pathway plays a crucial role in tumorigenesis and tumor progression. Akt protein modulates the function of numerous substrates related to the regulation of cell proliferation, such as cyclin dependent kinase inhibitors, including p27 and Cks1. The aim of this study was to investigate the immunohistochemical expressions of Akt, p27 and Cks1 proteins according to clinicopathological parameters such as gender, lymph node metastases, tumor invasion depth, the TNM stage and Lauren classification in gastric adenocarcinoma. METHODOLOGY: Immunohistochemical staining with monoclonal Akt, p27 and Cks1 antibodies was performed on the paraffin embedded specimens of 43 gastric adenocarcinomas. RESULTS: The expression of Akt was increased more in the adenocarcinomas that showed lymph node involvement (53.5%) than in the adenocarcinomas that did not (9.3%) (p=0.007). The expression of Cks1 was increased more in the adenocarcinomas that showed lymph node involvement (39.5%) than in the adenocarcinomas that did not (7%) (p<0.043). CONCLUSIONS: Akt and Cks1 are associated with lymph node metastasis in gastric adenocarcinoma. We suggest that Akt and Cks1 proteins might be related with poor prognosis in gastric adenocarcinoma.

Assessment of Fatigue and Associated Factors in Patients with Inflammatory Bowel Disease: A Questionnaire-Based Study.

Although fatigue is common in patients with inflammatory bowel disease (IBD), it often goes unrecognized and untreated. We investigated the degree of fatigue and associated factors in patients with IBD. A multicenter study involving 147 IBD patients was conducted at five academic hospitals from August 2019 to December 2021. Fatigue was evaluated using the validated Korean version of the Multidimensional Fatigue Inventory (MFI-K). Among 97 ulcerative colitis patients and 50 Crohn's disease patients, the mean total MFI-K score was 59.0 ± 5.5, which corresponded to a moderate-to-severe level of fatigue. Moderate-to-severe disease activity was found to be significantly associated with a higher general and physical fatigue subscale MFI-K score compared to remission-to-mild disease activity (17.6 ± 1.7 vs. 16.7 ± 2.0, p = 0.009), while the use of biologics was associated with a lower total MFI-K score (57.3 ± 5.0 vs. 59.5 ± 5.5, p = 0.031). In multiple linear regression, the total MFI-K score was positively correlated with a history of surgery for IBD, while it was negatively correlated with the use of biologics. Depression was positively correlated with the reduced motivation subscale score. The degree of fatigue in patients with IBD was high. Disease activity, the use of biologics, a history of surgery for IBD, and depression were associated with fatigue.

The ClC-2 Chloride Channel Activator, Lubiprostone, Improves Intestinal Barrier Function in Biopsies from Crohn's Disease but Not Ulcerative Colitis Patients.

The prostone analog, lubiprostone, is approved to manage constipation-predominant irritable bowel syndrome. Lubiprostone also protects intestinal mucosal barrier function in animal models of colitis. The aim of this study was to determine if lubiprostone improves barrier properties in isolated colonic biopsies from Crohn's disease (CD) and ulcerative colitis (UC) patients. Sigmoid colon biopsies from healthy subjects, CD and UC patients in remission, and CD patients with active disease were mounted in Ussing chambers. Tissues were treated with lubiprostone or vehicle to determine the effects on transepithelial electrical resistance (TER), FITC-dextran 4kD (FD4) permeability, and electrogenic ion transport responses to forskolin and carbachol. Localization of the tight junction protein, occludin, was determined by immunofluorescence. Lubiprostone significantly increased ion transport across control, CD and UC remission biopsies but not active CD. Lubiprostone selectively improved TER in both CD remission and active disease biopsies but not in control or UC biopsies. The improved TER was associated with increased membrane localization of occludin. Lubiprostone selectively improved barrier properties of biopsies from CD patients vs. UC and independent of an ion transport response. These data indicate that lubiprostone has potential efficacy in improving mucosal integrity in Crohn's disease.

Potential Oral Microbial Markers for Differential Diagnosis of Crohn's Disease and Ulcerative Colitis Using Machine Learning Models.

Although gut microbiome dysbiosis has been associated with inflammatory bowel disease (IBD), the relationship between the oral microbiota and IBD remains poorly understood. This study aimed to identify unique microbiome patterns in saliva from IBD patients and explore potential oral microbial markers for differentiating Crohn's disease (CD) and ulcerative colitis (UC). A prospective cohort study recruited IBD patients (UC: n = 175, CD: n = 127) and healthy controls (HC: n = 100) to analyze their oral microbiota using 16S rRNA gene sequencing. Machine learning models (sparse partial least squares discriminant analysis (sPLS-DA)) were trained with the sequencing data to classify CD and UC. Taxonomic classification resulted in 4041 phylotypes using Kraken2 and the SILVA reference database. After quality filtering, 398 samples (UC: n = 175, CD: n = 124, HC: n = 99) and 2711 phylotypes were included. Alpha diversity analysis revealed significantly reduced richness in the microbiome of IBD patients compared to healthy controls. The sPLS-DA model achieved high accuracy (mean accuracy: 0.908, and AUC: 0.966) in distinguishing IBD vs. HC, as well as good accuracy (0.846) and AUC (0.923) in differentiating CD vs. UC. These findings highlight distinct oral microbiome patterns in IBD and provide insights into potential diagnostic markers.

Real-life effectiveness and safety of tofacitinib treatment in patients with ulcerative colitis: a KASID multicenter cohort study.

Background: Tofacitinib is a small molecule that inhibits Janus kinase and has been reported to be effective in Western patients with ulcerative colitis (UC). However, the real-life data on tofacitinib in Asian UC patients are limited. Objective: To investigate the real-life effectiveness and safety of tofacitinib induction and maintenance treatment in Korean patients with UC. Design: This was a retrospective study on patients with UC who received tofacitinib treatment at 12 hospitals in Korea between January 2018 and November 2020. Methods: Clinical remission at week 52, defined as a partial Mayo score of ⩽2 with a combined rectal bleeding subscore and stool frequency subscore of ⩽1, was used as the primary outcome. Adverse events (AEs), including herpes zoster and deep vein thrombosis, were also evaluated. Results: A total of 148 patients with UC were started on tofacitinib. Clinical remission rates of 60.6%, 54.9%, and 52.8% were reported at weeks 16, 24, and 52, respectively. Clinical response rates of 71.8%, 67.6%, and 59.9% were reported at weeks 16, 24, and 52, respectively. Endoscopic remission rates at weeks 16 and 52 were 52.4% and 30.8% based on the Mayo endoscopic subscore and 20.7% and 15.2% based on the UC endoscopic index of severity (UCEIS), respectively. A higher UCEIS at baseline was negatively associated with clinical response [adjusted odds ratio (aOR): 0.774, p = 0.029] and corticosteroid-free clinical response (aOR: 0.782, p = 0.035) at week 52. AEs occurred in 19 patients (12.8%) and serious AEs in 12 patients (8.1%). Herpes zoster occurred in four patients (2.7%). One patient (0.7%) suffered from deep vein thrombosis. Conclusions: Tofacitinib was an effective induction and maintenance treatment with an acceptable safety profile in Korean patients with UC. Plain language summary: Real-life effectiveness and safety of tofacitinib treatment in Korean patients with ulcerative colitis Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disorder of the colonic mucosa that usually presents with bloody diarrhea and abdominal pain. Tofacitinib is a small molecule that inhibits Janus kinase and has been reported to be effective in Western patients with UC. However, real-life data on the effectiveness of tofacitinib in Asian patients with UC are limited. To investigate the real-life effectiveness and safety of tofacitinib treatment in Korean patients with UC, we retrospectively analyzed the data of 148 patients with UC who received tofacitinib treatment at 12 hospitals in Korea between January 2018 and November 2020. Clinical remission (i.e. complete improvement of symptoms) was achieved in 60.6% and 52.8% of patients at weeks 16 and 52, respectively. Endoscopic remission was achieved in 52.4% and 30.8% of patients at weeks 16 and 52, respectively. A higher baseline score of the UC endoscopic index of severity, which is one of the endoscopic indices that evaluate the severity of inflammation of the colon, was negatively associated with clinical response (i.e. partial improvement of symptoms). Adverse events (AEs) including herpes zoster and deep vein thrombosis occurred in 19 patients (12.8%) and serious AEs occurred in 12 patients (8.1%). Our real-life study shows that tofacitinib is a clinically effective treatment for Korean patients with UC, and the incidence of AEs was also similar to those observed in other real-world studies.

Changes in fecal metabolic and lipidomic features by anti-TNF treatment and prediction of clinical remission in patients with ulcerative colitis.

Background: Therapeutic targets for ulcerative colitis (UC) and prediction models of antitumor necrosis factor (TNF) therapy outcomes have not been fully reported. Objective: Investigate the characteristic metabolite and lipid profiles of fecal samples of UC patients before and after adalimumab treatment and develop a prediction model of clinical remission following adalimumab treatment. Design: Prospective, observational, multicenter study was conducted on moderate-to-severe UC patients (n = 116). Methods: Fecal samples were collected from UC patients at 8 and 56 weeks of adalimumab treatment and from healthy controls (HC, n = 37). Clinical remission was assessed using the Mayo score. Metabolomic and lipidomic analyses were performed using gas chromatography mass spectrometry and nano electrospray ionization mass spectrometry, respectively. Orthogonal partial least squares discriminant analysis was performed to establish a remission prediction model. Results: Fecal metabolites in UC patients markedly differed from those in HC at baseline and were changed similarly to those in HC during treatment; however, lipid profiles did not show these patterns. After treatment, the fecal characteristics of remitters (RM) were closer to those of HC than to those of non-remitters (NRM). At 8 and 56 weeks, amino acid levels in RM were lower than those in NRM and similar to those in HC. After 56 weeks, levels of 3-hydroxybutyrate, lysine, and phenethylamine decreased, and dodecanoate level increased in RM similarly to those in HC. The prediction model of long-term remission in male patients based on lipid biomarkers showed a higher performance than clinical markers. Conclusion: Fecal metabolites in UC patients markedly differ from those in HC, and the levels in RM are changed similarly to those in HC after anti-TNF therapy. Moreover, 3-hydroxybutyrate, lysine, phenethylamine, and dodecanoate are suggested as potential therapeutic targets for UC. A prediction model of long-term remission based on lipid biomarkers may help implement personalized treatment.

Psychological Effects and Medication Adherence among Korean Patients with Inflammatory Bowel Disease during the Coronavirus Disease 2019 Pandemic: A Single-Center Survey.

BACKGROUND AND AIM: This study evaluated the impact of coronavirus disease 2019 (COVID-19) on the mental health of inflammatory bowel disease (IBD) patients. We quantified anxiety, depression, and medication adherence among IBD patients through a single-center survey in South Korea during the COVID-19 pandemic. METHODS: An electronic survey was made available to patients at the IBD clinic in Daejeon St. Mary's hospital from July 2021 to September 2021. The validated Hospital Anxiety and Depression Scale (HADS) was used to assess depression and anxiety. The Korean version of the Medication Adherence Rating Scale (KMARS) questionnaire was used to assess medication adherence. RESULTS: In total, 407 patients (56.5%; ulcerative colitis, 43.5%; Crohn's disease) participated in the survey. Among the respondents, 14.5% showed significant anxiety and 26.3% showed significant depression. Female sex, presence of mental disease, unvaccinated status, and the presence of Crohn's disease were associated with greater risks of anxiety and depression. Among medications, immunomodulators were associated with a greater risk of anxiety. In terms of KMARS, patients reported favorable medication adherence despite the psychological burden of the pandemic. The KMARS score was 7.3 ± 1.5 (mean ± SD) of 10.0 points. High anxiety and depression were associated with a slight decrease in medication adherence. CONCLUSIONS: COVID-19 has increased anxiety and depression among IBD patients, whose medication adherence has nevertheless remained good. Furthermore, anxiety and depression were found to have a negative correlation with adherence. Our results provide insights concerning psychological response and medication adherence among IBD patients in South Korea during the COVID-19 pandemic.

Anastomotic leakage and chronic presacral sinus after transanal total mesorectal excision (taTME) for rectal cancer: A comparative study to laparoscopic TME.

BACKGROUND: Several studies have shown that there are no significant differences in anastomotic leakage associated with Transanal total mesorectal excision (taTME) versus laparoscopic TME (lapTME) for rectal cancer; however, little is known about late anastomotic leakage, such as that primarily found in the chronic presacral sinus. We aimed to compare the occurrence of anastomotic leakage and chronic presacral sinus in rectal cancer for taTME and lapTME. METHODS: In this retrospective cohort study, data were collected for patients with rectal cancer who underwent surgery between January 2009 and September 2019. Of the 220 patients included in this study, 182 were in the lapTME group and 38 in the taTME group. We compared factors associated with anastomotic leakage and chronic presacral sinus formation between the two groups. A binary-logistic model was used to determine the risk factors for chronic presacral sinus. RESULTS: Anastomotic leakage occurred in six patients (15.8%) in the taTME group and 36 patients (19.7%) in the lapTME group. Chronic presacral sinus occurred in three patients (7.9%) in the taTME group and 15 patients (8.2%) in the lapTME group. There was no significant difference in anastomotic leakage or chronic presacral sinus between groups (P = 0.569 and P = 1.000, respectively). Pathologic stage III or higher was significantly associated with chronic presacral sinus formation (P = 0.006). CONCLUSION: There were no significant differences between taTME and lapTME regarding the incidence of anastomotic leakage or chronic presacral sinus. Almost one-third of anastomotic leakages developed into chronic presacral sinus.

Reliability and Validity of Korean Version of Crohn's and Ulcerative Colitis Questionnaire-8.

Background: Patients with inflammatory bowel disease (IBD) have a decreased quality of life (QoL), the improvement of which is a treatment goal. The CUCQ-8 is a verified simple and effective QoL measurement tool. We validated the Korean version of CUCQ-8 with the approval of its developer. Methods: We investigated the correlation between the Korean version of CUCQ-8 and the IBDQ-32 in patients with IBD. Results: In all, 147 subjects (male, 97 (66.0%); female, 50 (34.0%); mean age 36.2 ± 13.5 years) were analyzed. Cronbach's alpha coefficient of the CUCQ-8 was 0.833, indicating very high internal consistency. The Korean version of the CUCQ-8 showed a significant correlation with the IBDQ-32 and its subscales (correlation coefficient, >0.75). Conclusions: The Korean version of the CUCQ-8 has high reliability and construct validity and can be used to evaluate the QoL of patients with IBD.

Additive effect of probiotics (Mutaflor) on 5-aminosalicylic acid therapy in patients with ulcerative colitis.

BACKGROUND/AIMS: In ulcerative colitis (UC) patients, Escherichia coli Nissle 1917 (EcN) is equivalent to mesalazine for preventing disease relapse; however, evidence of the ability of EcN to increase health-related quality of life or induce remission remains scarce. We investigated the efficacy of EcN as an add-on therapy for UC. METHODS: In this multicentre, double-blind, randomised, placebo-controlled study, a total of 133 UC patients were randomly assigned to receive either EcN or placebo once daily for 8 weeks. Inflammatory bowel disease questionnaire (IBDQ) scores (primary endpoint) and clinical remission and response rates (secondary endpoints) were compared (Clinical trial registration number: NCT04969679). RESULTS: In total, 118 patients (EcN, 58; placebo, 60) completed the study. The number of patients reaching the primary endpoint did not differ between the EcN and placebo groups (30 [51.7%] vs. 31 [51.7%]; per-protocol analysis, p = 1.0; intention-to-treat analysis, p = 0.86). However, significantly fewer patients in the EcN group exhibited a decreased IBDQ score (1 [1.7%] vs. 8 [13.3%]; per-protocol analysis, p = 0.03; intention- to-treat analysis, p = 0.02). Moreover, a significantly higher number of patients in the EcN group displayed clinical response at 4 weeks (23 [39.7%] vs. 13 [21.7%], p = 0.04) and endoscopic remission at 8 weeks (26 [46.4%] vs. 16 [27.1%], p = 0.03). CONCLUSION: Although the number of patients reaching the primary endpoint did not differ between the EcN and placebo groups, EcN was found to be safe and effective in preventing the exacerbation of IBDQ scores and achieving clinical responses and endoscopic remission in patients with mild-to-moderate UC.