Single-Cell Network-Based Drug Repositioning for Discovery of Therapies against Anti-Tumour Necrosis Factor-Resistant Crohn's Disease.

Primary and secondary non-response affects approximately 50% of patients with Crohn's disease treated with anti-tumour necrosis factor (TNF) monoclonal antibodies. To date, very little single cell research exists regarding drug repurposing in Crohn's disease. We aimed to elucidate the cellular phenomena underlying resistance to anti-TNF therapy in patients with Crohn's disease and to identify potential drug candidates for these patients. Single-cell transcriptome analyses were performed using data (GSE134809) from the Gene Expression Omnibus and Library of Integrated Network-Based Cellular Signatures L1000 Project. Data aligned to the Genome Reference Consortium Human Build 38 reference genome using the Cell Ranger software were processed using the Seurat package. To capture significant functional terms, gene ontology functional enrichment analysis was performed on the marker genes. For biological analysis, 93,893 cells were retained (median 20,163 genes). Through marker genes, seven major cell lineages were identified: B-cells, T-cells, natural killer cells, monocytes, endothelial cells, epithelial cells, and tissue stem cells. In the anti-TNF-resistant samples, the top 10 differentially expressed genes were HLA-DQB-1, IGHG1, RPS23, RPL7A, ARID5B, LTB, STAT1, NAMPT, COTL1, ISG20, IGHA1, IGKC, and JCHAIN, which were robustly distributed in all cell lineages, mainly in B-cells. Through molecular function analyses, we found that the biological functions of both monocyte and T-cell groups mainly involved immune-mediated functions. According to multi-cluster drug repurposing prediction, vorinostat is the top drug candidate for patients with anti-TNF-refractory Crohn's disease. Differences in cell populations and immune-related activity within tissues may influence the responsiveness of Crohn's disease to anti-TNF agents. Vorinostat may serve as a promising novel therapy for anti-TNF-resistant Crohn's disease.

Risk of Metachronous Colorectal Advanced Neoplasia and Cancer in Patients With 3-4 Nonadvanced Adenomas at Index Colonoscopy: A Systematic Review and Meta-Analysis.

INTRODUCTION: This systematic review and meta-analysis evaluated the available evidence on the risk of metachronous advanced neoplasia (AN) and colorectal cancer (CRC) in patients with 3-4 nonadvanced adenomas (NAAs). METHODS: We searched MEDLINE, EMBASE, and Cochrane Library databases up to January 2021 for studies evaluating metachronous AN and CRC risk by comparing 3 groups (1-2 vs 3-4 vs ≥5 NAAs) at index colonoscopy. The estimates for risk of metachronous AN and CRC were evaluated using random-effects models. RESULTS: Fifteen studies (n = 36,375) were included. The risk of metachronous AN was significantly higher in the 3-4 NAAs group than in the 1-2 NAAs group (relative risk [RR] 1.264, 95% confidence interval [CI] 1.053-1.518, P = 0.012; I2 = 0%); there was no difference between the ≥ 5 NAAs and 3-4 NAAs groups (RR 1.962, 95% CI 0.972-3.958, P = 0.060; I2 = 68%). The risks of metachronous CRC between the 1-2 NAAs and 3-4 NAAs groups (RR 2.663, 95% CI 0.391-18.128, P = 0.317; I2 = 0%) or the 3-4 NAAs and ≥ 5 NAAs groups (RR 1.148, 95% CI 0.142-9.290, P = 0.897; I2 = 0%) were not significantly different. DISCUSSION: Although the risk of metachronous AN was greater in the 3-4 NAAs group than in the 1-2 NAAs group, the risk of metachronous AN and CRC between the 3-4 NAAs and ≥ 5 NAAs groups was not different. This suggests that further studies on metachronous AN and CRC risk in the 3-4 NAAs group are warranted to confirm a firm ≥5-year interval surveillance colonoscopy.

Artificial intelligence-based measurement outperforms current methods for colorectal polyp size measurement.

OBJECTIVES: An accurate polyp size estimation during colonoscopy is crucial to determine the surveillance interval and predict the risk of malignant progression. However, there is a high degree of subjectivity in estimating polyp size among endoscopists in clinical practice. We aimed to assess the efficacy of a novel method that uses artificial intelligence (AI) to measure the size of colon polyps and compare it with current approaches. METHODS: Using the W-Net model for vessel segmentation and based on retinal image datasets (DRIVE, STARE, CHASE-DB, and HRF) and colonoscopy images, we developed the bifurcation-to-bifurcation (BtoB) distance measuring method and applied it to endoscopic images. Measurements were compared with those obtained by eight endoscopists (four expert and four trainees). Diagnostic ability and reliability were evaluated using Lin's concordance correlation coefficients (CCCs) and Bland-Altman analyses. RESULTS: For both experts and trainees, visually estimated sizes of the same polyp were significantly inconsistent depending on the camera view used (P < 0.001). Bland-Altman analyses showed that there was a trend toward underestimation of the sizes of the polyps in both groups, especially for polyps larger than 10 mm. The new technique was highly accurate and reliable in measuring the size of colon polyp (CCC, 0.961; confidence interval 0.926-0.979), clearly outperforming the visual estimation and open biopsy forceps methods. CONCLUSION: The new AI measurement method improved the accuracy and reliability of polyp size measurements in colonoscopy images. Incorporating AI might be particularly important to improve the efficiency of trainees at estimating polyp size during colonoscopy.

Seasonal variations in the diagnosis of the top 10 cancers in Korea: A nationwide population-based study using a common data model.

BACKGROUND AND AIM: A better understanding of seasonal variations in cancer diagnosis may be the first step toward optimal resource distribution in the National Cancer Screening Program (NCSP). This study aimed to identify seasonal variations in the diagnosis of the top 10 major cancers in Korea. METHODS: We conducted a retrospective, observational cohort study in participants aged ≥ 20 years between 2012 and 2016 from the Health Insurance Review and Assessment-National Patient Sample database, previously converted to a common data model. We assessed the overall seasonal variations in the 10 major cancers. RESULTS: We analyzed the following top 10 cancers: stomach (n = 3435), colorectal (n = 5368), liver (n = 7605), pancreatic (n = 2946), gallbladder (n = 899), lung (n = 1598), prostate (n = 2897), thyroid (n = 1966), breast (n = 1313), and kidney (n = 668) cancers. All cancers showed similar seasonal variations in diagnosis, with a significant winter peak. A winter peak in diagnosis was observed for NCSP-covered cancers, such as stomach, colon, liver, and breast cancers, as well as other cancers not covered by the NCSP. The winter peak for cancer diagnosis was the highest for breast cancer (74.4%) followed by thyroid (51.0%) and stomach cancers, whereas it was the lowest for pancreatic cancer followed by prostate and colorectal cancers. CONCLUSIONS: Significant seasonal variations were found in the diagnosis of the top 10 major cancers, with a winter peak, which may be explained by the participants' behavior pattern with respect to the NCSP. Our findings suggest that trading off of NCSP healthcare resources between winter and other seasons may be beneficial.

Real-World Use of Colonoscopy in an Older Population: A Nationwide Standard Cohort Study Using a Common Data Model.

BACKGROUNDS AND AIMS: Rapid population aging is considered to be a major factor in increased colonoscopy use in Korea. However, real-world use of colonoscopy in older populations is rarely evaluated using Korean databases. METHODS: We conducted a retrospective, observational cohort study of individuals aged over 20 years between 2012 and 2017. We used the Health Insurance Review and Assessment-National Patient Samples database, previously converted to the standardized Observational Medical Outcomes Partnership-Common Data Model. The use of diagnostic colonoscopy and colonoscopic polypectomy was evaluated, stratified by age group and sex. RESULTS: During the study period, we captured data from the database on 240,406 patients who underwent diagnostic colonoscopy and 88,984 who underwent colonoscopic polypectomy. During the study period, use of diagnostic colonoscopy and colonoscopic polypectomy steadily increased, but both procedures were most significantly increased in the 65- to 85-year group compared to other age groups (p < 0.05). Average ages for both procedures significantly increased in the most recent 3 years (p < 0.05). Polypectomy rates for men plateaued in the 50- to 64-year age group, but rates for women steadily increased up to the 65- to 85-year group. Polypectomy rates were higher for men than for women in all index years. CONCLUSIONS: The use of diagnostic colonoscopy and colonoscopic polypectomy significantly increased in the 65- to 85-year age group. Our findings suggest that more available colonoscopy resources should be allocated to older populations, considering the aging society in Asian countries.

Pretreatment with Ranitidine Bismuth Citrate May Improve Success Rates of Helicobacter pylori Eradication: A Prospective, Randomized, Controlled and Open-Label Study.

Effective Helicobacter pylori (H. pylori) eradication is a major public health concern; however, eradication failure rates with the standard triple therapy remain high. We aimed to investigate the effectiveness and tolerability of ranitidine bismuth citrate (RBC) pretreatment before standard triple therapy for H. pylori eradication. A prospective, randomized, controlled, and open-label clinical trial was conducted from June to December 2019. H. pylori eradication rate, safety, and tolerability were compared between the standard treatment group (esomeprazole, amoxicillin, and clarithromycin for 7 days) and RBC pretreatment group (RBC for 2 weeks before standard triple therapy). This trial ended earlier than estimated owing to the N-nitrosodimethylamine concerns with ranitidine. Success rates of H. pylori eradication were 80.9% and 67.3% in the RBC pretreatment (n = 47) and standard treatment (n = 52) (p = 0.126) groups, respectively. Our trial was discontinued earlier than planned; however, a statistical significance would be achieved by expansion of our data (p = 0.031) if patient enrollment numbers reached those initially planned. Adverse event rates were comparable between groups (25.5% in the pretreatment group vs. 28.8% in the standard treatment group), without serious event. Tolerability was excellent in both groups, recorded as 97.9% and 100% in the pretreatment and standard treatment groups, respectively. Compared with the standard triple regimen, RBC pretreatment for 2 weeks may achieve higher H. pylori eradication rates, with excellent safety and tolerability. However, this study necessitates further validation as it was discontinued early owing to the N-nitrosodimethylamine issues of ranitidine.

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.

Emerging trends of inflammatory bowel disease in South Korea: A nationwide population-based study.

BACKGROUND AND AIM: Little is known regarding the exact burden of inflammatory bowel disease (IBD) in Asian countries because previous epidemiologic studies were hospital based. We aimed to develop and validate an operational definition of IBD cases from health insurance claims data and to examine the epidemiological features of IBD in Korea. METHODS: We analyzed stratified sample data from the Korean Health Insurance Review and Assessment (2010-2016) database using 12 different definitions and applied the best definition to the entire (2007-2016) dataset. RESULTS: The definition that combined the International Classification of Disease 10th revision code with IBD-specific medications had the best performance characteristics among the 12 tested definitions. During the 8-year study period, IBD prevalence increased from 25 345 in 2009 to 47 444 in 2016. Over that period, the prevalence of Crohn's disease increased 1.9-fold (from 16.0/100 000 in 2009 to 29.6/100 000 in 2016) and that of ulcerative colitis increased 1.6-fold (from 41.4/100 000 in 2009 to 66.0/100 000 in 2016). Similarly, the estimated incidence of Crohn's disease also increased 1.2-fold (from 2.4 to 2.9 per 100 000) and that of ulcerative colitis rose 1.3-fold (from 4.0 to 5.3 per 100 000). During the study period, the predominant increase in IBD incidence was among younger individuals, especially those aged < 30 years. CONCLUSION: Patients with IBD can be accurately identified using Korean insurance claims data by combining information regarding the International Classification of Disease 10th revision codes and the IBD medications used. The prevalence of IBD continues to increase, with an apparent shift toward younger (< 30 years) age groups.

Risk of Interval Cancer in Fecal Immunochemical Test Screening Significantly Higher During the Summer Months: Results from the National Cancer Screening Program in Korea.

OBJECTIVES: This study aimed to evaluate the impact of seasonal variations in climate on the performance of the fecal immunochemical test (FIT) in screening for colorectal cancer in the National Cancer Screening Program in Korea. METHODS: Data were extracted from the National Cancer Screening Program databases for participants who underwent FIT between 2009 and 2010. We compared positivity rates, cancer detection rates, interval cancer rates, positive predictive value, sensitivity, and specificity for FIT during the spring, summer, fall, and winter seasons in Korea. RESULTS: In total, 4,788,104 FIT results were analyzed. FIT positivity rate was lowest during the summer months. In the summer, the positive predictive value of FIT was about 1.1 times (adjusted odds ratio (aOR) 1.08, 95% confidence interval (CI) 1.00-1.16) higher in the overall FIT group and about 1.3 times (aOR 1.29, 95% CI 1.10-1.50) higher in the quantitative FIT group, compared to those in the other seasons. Cancer detection rates, however, were similar regardless of season. Interval cancer risk was significantly higher in the summer for both the overall FIT group (aOR 1.16, 95% CI 1.07-1.27) and the quantitative FIT group (aOR 1.31, 95% CI 1.12-1.52). In addition, interval cancers in the rectum and distal colon were more frequently detected in the summer and autumn than in the winter. CONCLUSIONS: The positivity rate of FIT was lower in the summer, and the performance of the FIT screening program was influenced by seasonal variations in Korea. These results suggest that more efforts to reduce interval cancer during the summer are needed in population-based screening programs using FIT, particularly in countries with high ambient temperatures.

Probiotics Ameliorate Stool Consistency in Patients with Chronic Constipation: A Randomized, Double-Blind, Placebo-Controlled Study.

BACKGROUND/AIMS: The efficacy of probiotics for improving clinical symptoms, altering the fecal microbiota, and regulating serum immune cytokine levels was investigated in patients with irritable bowel syndrome-constipation (IBS-C) or functional constipation (FC). METHODS: A randomized, double-blind, placebo-controlled trial was conducted at Kyung Hee University Hospital between October 2016 and February 2017. Consecutive 18-75-year-old patients with diagnosis of IBS-C or FC (based on Rome IV criteria) consumed probiotics (3.0 × 108 CFU/g Streptococcus thermophilus MG510 and 1.0 × 108 CFU/g Lactobacillus plantarum LRCC5193) or a placebo daily for 4 weeks (weeks 1-4) and were followed up for a 4-week washout period without intervention (weeks 5-8). The primary outcomes of the study were Bristol Stool Form Scale and Complete Spontaneous Bowel Movements (CSBM). Efficacy was assessed by per protocol. RESULTS: Stool consistency measured by the Bristol Stool Form Scale was significantly better in the probiotic group (n = 88) than in the placebo group (n = 83) at 4 and 8 weeks (3.7 ± 1.1 vs. 3.1 ± 1.1 at 8 weeks, P = 0.002). No significant difference was found in CSBM. The quality of life was significantly better in the probiotic group than in the placebo group at 4 weeks (P = 0.044) and 8 weeks (P = 0.049). The relative abundance of L. plantarum among the fecal microbiomes was significantly greater in the probiotic group than in the placebo group at 4 weeks (P = 0.029). However, the levels of other microbiomes and of serum cytokines (IL-10/IL-12 ratio and TNF-α) did not differ significantly between the two groups. CONCLUSIONS: Probiotics significantly ameliorated stool consistency in patients with chronic constipation. In addition, the beneficial effect of L. plantarum on stool consistency remained after the probiotic supplementation was discontinued. The mechanism whereby probiotics benefit patients with chronic constipation should be clarified in further studies.

Age-adapted Variation in Screening Interval of Fecal Immunochemical Test May Improve its Participation and Colonoscopy Acceptance.

GOALS: We determined appropriate intervals for administering the fecal immunochemical test (FIT) and performance outcomes in an Asian national colorectal cancer (CRC) screening program. BACKGROUND: The optimal interval for FIT in CRC screening is unclear, especially in Asian populations. STUDY: Between January 2009 and December 2015, 13,480 individuals aged 50 years or older with an initial negative FIT result underwent 2 rounds of FIT screening at intervals of 1 (annual group, 5333), 2 (biennial group, 7363), or 3 years (triennial group, 784). Positive rates of FIT, colonoscopy acceptance, colonoscopy findings, and detection rates for CRC and advanced neoplasia were compared according to FIT intervals. RESULTS: The overall positivity rate of FIT in the second screening round was significantly higher in men and in older subjects than in the entire sample. Younger subjects were less likely to undergo annual FIT (36.0% vs. 46.4%, P<0.001). The colonoscopy acceptance rate was decreased in the biennial and triennial groups compared with an annual group among younger subjects (odds ratio, 0.56; 95% confidence interval, 0.33-0.95 for the biennial group vs. odds ratio, 0.19; 95% confidence interval, 0.03-1.37 for the triennial group). Detection rates for CRC and advanced neoplasia in the second round were significantly higher and accompanied by increased FIT screening intervals in older, but not younger subjects. CONCLUSIONS: Age-adapted variation in FIT screening intervals, such as annual screening for elderly subjects and biennial screening for younger subject, may improve FIT participation and colonoscopy acceptance.

Evaluation of scoring systems without endoscopic findings for predicting outcomes in patients with upper gastrointestinal bleeding.

BACKGROUND: Risk scoring systems are used to evaluate patients with upper gastrointestinal bleeding (UGIB). We compared Glasgow-Blatchford score (GBS), modified GBS (mGBS), and Pre-endoscopy Rockall score (Pre-E RS) for immediate application without endoscopic findings in predicting the need of interventions and the 30-day mortality in patients with UGIB. METHODS: Patients who visited the emergency room with UGIB from January 2007 to June 2016 were included. GBS, mGBS, and Pre-E RS were obtained for all patients. The area under the receiver-operating characteristic curves (AUC) was used to assess the accuracy of the scoring systems to determine the need for interventions and 30-day mortality. Also, we investigated the potential cutoff scores for predicting 30-day mortality and the need for interventions. RESULTS: In predicting the need for interventions, GBS (AUC = 0.727) and mGBS (AUC = 0.733) outperformed Pre-E RS (AUC = 0.564, P < 0.0001). In predicting 30-day mortality, Pre-E RS (AUC = 0.929) outperformed GBS (AUC = 0.664, P < 0.0001) and mGBS (AUC = 0.652, P < 0.0001). Based on AUC analyses of sensitivities and specificities, the optimal cutoff mGBS and GBS for the need for interventions was 9 (70.71% sensitivity, 89.35% specificity) and 9 (73.57% sensitivity, 82.90% specificity) respectively, and optimal cutoff Pre-E RS for 30-day mortality was 4 (88.0% sensitivity, 97.52% specificity). CONCLUSIONS: GBS and mGBS are considered to be moderately accurate in making an early decision about the need of interventions in patients with UGIB. Pre-E RS is considered to be highly accurate in early detection of patients at high risk for 30-day mortality without endoscopic findings. In addition, we suggested potential cutoff scores to predict the need of interventions for GBS and mGBS, and 30-day mortality for Pre-E RS. Further studies are needed to confirm the clinical applicability of results.

Fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography for the detection of proximal synchronous lesions in patients with obstructive colorectal cancer.

BACKGROUND AND AIM: We aimed to investigate the ability of fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) to detect synchronous neoplasms, specifically obstructive colorectal cancer (CRC) and CRC in the proximal colon and to suggest a management strategy based on FDG PET/CT findings. METHODS: From the CRC surgery database of our institution, 518 patients with obstructive CRC whose proximal colon could not be examined by colonoscopy and who underwent preoperative FDG PET/CT were eligible for this study. Of these, final analyses were performed in 345 patients who had reference standards for the proximal colon, which were a surgical colectomy specimen and/or postsurgical colonoscopy. The per-patient and per-lesion performances of FDG PET/CT for synchronous CRC diagnosis were determined. RESULTS: Of 345 patients, 14 (4.1%) had 14 proximal synchronous CRCs. Thirty-four patients showed 39 areas of abnormal FDG uptake on PET/CT in the colon proximal to the obstructive CRC. PET/CT detected all of the 14 proximal synchronous CRCs. The per-patient PET/CT sensitivity, specificity, positive predictive value, and negative predictive value for proximal synchronous CRC were 100%, 93.9%, 41.2%, and 100%, respectively. Per-lesion values were 100%, 92.6%, 35.9%, and 100%, respectively. The per-lesion sensitivity and negative predictive value of PET/CT for advanced adenoma were 45.5% and 92.7%, respectively. CONCLUSIONS: The FDG PET/CT shows a high sensitivity and negative predictive value for the detection of proximal synchronous CRC in patients with obstructive CRC, enabling negative findings in the proximal colon on PET/CT to definitively exclude proximal synchronous CRC. Preoperative PET/CT recommended to determine the proper surgical plan in patients with obstructive CRC.

Does Stenting as a Bridge to Surgery in Left-Sided Colorectal Cancer Obstruction Really Worsen Oncological Outcomes?

BACKGROUND: Although self-expandable metal stents are used as a bridge to surgery in patients with colorectal cancer obstruction, their long-term oncological outcomes are unclear. OBJECTIVE: The aim of this study was to investigate long-term oncological outcomes of self-expandable metal stents as a bridge to surgery (stent group) compared with direct surgery (direct operation group) in patients with left-sided colorectal cancer obstruction. DESIGN: This was a retrospective chart review. SETTINGS: This study was conducted at a single tertiary academic center. PATIENTS: Of 113 patients who underwent curative surgery for left-sided colorectal cancer obstruction at Asan Medical Center between 2005 and 2011, 42 underwent direct surgery and 71 underwent self-expandable metal stent insertion followed by elective surgery. After 1:1 propensity-score matching, 42 patients were enrolled in both groups, and their postsurgical outcomes were compared. MAIN OUTCOME MEASURES: The primary outcomes of this study were long-term oncological outcomes, including overall survival and recurrence-free survival of patients in both groups. RESULTS: Three- and 5-year overall survival rates were similar in the stent (87.0% and 71.0%) and direct operation (76.4% and 76.4%) groups (p = 0.931). Three- and 5-year recurrence-free survival rates were also similar in the stent (91.9% and 66.4%) and direct operation (81.2% and 71.2%) groups (p = 0.581), as were postsurgical complication rates (9.5% and 16.7%; p = 0.344). No patient in either group experienced a permanent stoma. LIMITATIONS: This study was limited by its small patient numbers and retrospective nature. CONCLUSIONS: The long-term oncological outcomes of self-expandable metal stents as a bridge to surgery may not be inferior to those of direct surgery for left-sided colorectal cancer obstruction.

Influences of XDH genotype by gene-gene interactions with SUCLA2 for thiopurine-induced leukopenia in Korean patients with Crohn's disease.

BACKGROUND: The impact of genetic variation in the thiopurine S-methyltransferase (TPMT) gene on thiopurine-induced leukopenia has been well demonstrated. Although xanthine dehydrogenase (XDH) is the second major contributor to azathioprine breakdown, polymorphisms in XDH have rarely been studied in IBD patients. We aim to access association between XDH variants and thiopurine-induced leukopenia by gene-gene interaction in a Crohn's disease (CD) population. STUDY: A total of 964 CD patients treated with thiopurines were recruited from a tertiary referral center. The association between four XDH variants (p.Gly172Arg, p.Asn1109Thr, p.Arg149Cys, and p.Thr910Lys) and thiopurine-induced leukopenia was analyzed in cases with early leukopenia (n = 66), late leukopenia (n = 264), and in controls without leukopenia (n = 632). Three non-synonymous SNPs, which we previously reported association with thiopurine-induced leukopenia, NUDT15 (p.Arg139Cys), SUCLA2 (p.Ser199Thr), and TPMT *3C were selected for epistasis analysis with the XDH variants. RESULTS: There was no significant association for two variants of XDH and thiopurine-induced leukopenia. In the epistasis analysis, only XDH (p.Asn1109Thr) * SUCLA2 (p.Ser199Thr) showed a statistically significant association with early leukopenia [odds ratio (OR) = 0.16; p = 0.03]. After genotype stratification, a positive association on the background of SUCLA2 wild-type (199Ser) between the XDH (p.Asn1109Thr) and early leukopenia (OR = 4.39; p = 0.01) was detected. CONCLUSION: Genes associated with thiopurine-induced leukopenia can act in a complex interactive manner. Further studies are warranted to explore the mechanisms underlying the effects of the combination of XDH (p.Asn1109Thr) and SUCLA2 (199Ser) on thiopurine-induced leukopenia.

Long-Term Outcomes of Infliximab Treatment in 582 Korean Patients with Crohn's Disease: A Hospital-Based Cohort Study.

BACKGROUND AND AIMS: To date, no large-scale studies have evaluated long-term outcomes of infliximab (IFX) treatment in Korean patients with Crohn's disease (CD). METHODS: We analyzed long-term clinical responses to IFX in 582 Korean CD patients who received scheduled IFX treatments at Asan Medical Center. Clinical responses were defined as maintaining IFX without major abdominal surgery (MAS) or dose intensification. RESULTS: Between February 2002 and July 2015, a total of 11,990 IFX infusions were administered to 582 Korean patients with CD over a median period of 36 months. At the end of follow-up, 316 (54.3 %) were still receiving IFX without MAS (71 patients, 12.2 %) or dose intensification (86 patients, 14.8 %). IFX was stopped in 109 (18.7 %) patients because of a loss of response (48 patients, 8.2 %), adverse events (30 patients, 5.2 %), or patient preferences or problems with reimbursement (31 patients, 5.3 %). The cumulative survival for maintenance of IFX without MAS or dose intensification was 89.0, 75.9, 68.3, and 50.8 % at 1, 2, 3, and 5 years, respectively. Multivariate regression analysis identified older age at the initiation of IFX (≥40 years, P = 0.006) and a longer disease duration (≥3 years, P = 0.020) as independent positive predictors of a poorer response to IFX. CONCLUSIONS: The long-term efficacy of IFX in a large, real-life cohort of Korean patients with CD appears to be similar to that in previously published Western studies. Our findings support the early use of IFX to obtain better clinical outcomes.

The Clinical Outcomes of Lower Gastrointestinal Bleeding Are Not Better than Those of Upper Gastrointestinal Bleeding.

The incidence of lower gastrointestinal bleeding (LGIB) is increasing; however, predictors of outcomes for patients with LGIB are not as well defined as those for patients with upper gastrointestinal bleeding (UGIB). The aim of this study was to identify the clinical outcomes and the predictors of poor outcomes for patients with LGIB, compared to outcomes for patients with UGIB. We identified patients with LGIB or UGIB who underwent endoscopic procedures between July 2006 and February 2013. Propensity score matching was used to improve comparability between LGIB and UGIB groups. The clinical outcomes and predictors of 30-day rebleeding and mortality rate were analyzed between the two groups. In total, 601 patients with UGIB (n = 500) or LGIB (n = 101) were included in the study, and 202 patients with UGIB and 101 patients with LGIB were analyzed after 2:1 propensity score matching. The 30-day rebleeding and mortality rates were 9.9% and 4.5% for the UGIB group, and 16.8% and 5.0% for LGIB group, respectively. After logistic regression analysis, the Rockall score (P = 0.013) and C-reactive protein (CRP; P = 0.047) levels were significant predictors of 30-day mortality in patients with LGIB; however, we could not identify any predictors of rebleeding in patients with LGIB. The clinical outcomes for patients with LGIB are not better than clinical outcomes for patients with UGIB. The clinical Rockall score and serum CRP levels may be used to predict 30-day mortality in patients with LGIB.

Efficacy of early immunomodulator therapy on the outcomes of Crohn's disease.

BACKGROUND: The natural course of Crohn's disease (CD), with continuing relapses and remissions, leads to irreversible intestinal damage. Early adoption of immunomodulator therapy has been proposed in order to address this; however, it is still uncertain whether early immunomodulator therapy could affect the natural course of the disease in real practice. We evaluated the efficacy of such therapy on the prognosis of newly diagnosed patients with CD. METHODS: This retrospective study included 168 patients who were newly diagnosed with CD and who started treatment at Severance Hospital, Seoul, Korea between January 2006 and March 2013. The short- and long-term outcomes were compared between patients treated with early immunomodulator therapy and those treated with conventional therapy. RESULTS: A Kaplan-Meier analysis identified that administration of immunomodulators within 6 months after diagnosis of CD was superior to conventional therapy in terms of clinical remission and corticosteroid-free remission rates (P=0.043 and P=0.035). However, P=0.827). Patients with a baseline elevated CRP level were more likely to relapse (P<0.005). Drug-related adverse events were more frequent in the early immunomodulator therapy group than in the conventional therapy group P=0.029). CONCLUSIONS: Early immunomodulator therapy was more effective than conventional therapy in inducing remission, but not in preventing relapse. Baseline high CRP level was a significant indicator of relapse.

Demographic Characteristics and Economic Burden of Clostridioides difficile Infection in Korea: A Nationwide Population-Based Study after Propensity Score Matching.

Clostridioides difficile infection (CDI) poses a considerable threat to global public health. However, there have been insufficient propensity score-matched data on its demographic characteristics and economic burden. Using nationwide claims data, we assessed longitudinal changes in the demographic characteristics and economic burden of CDI between 2011 and 2019 after propensity score matching. We performed a regression analysis to compare the differences in the length of hospital stay and medical costs between patients with CDI and controls (gastroenteritis and colitis). The CDI hospitalization rate increased 2.9-fold between 2011 and 2019. The CDI group had higher comorbidity index scores and was more frequently diagnosed at tertiary hospitals and in the Seoul region than the control group (all p < 0.001). The annual incidence rate of CDI/10,000 persons significantly increased in both sexes and all age groups. The length of hospital stay and medical costs were 3.3-fold and 5.0-fold greater, respectively, in the CDI than in the control group (both p < 0.001). Although the length of hospital stay decreased, total medical costs increased in all age groups and both sexes between 2011 and 2019 (all p < 0.001). When compared with the control group, the CDI-attributable length of hospital stay and medical cost were greater by 15.3 days and KRW 3413 (×103), respectively, after matching. In conclusion, CDI incidence, particularly among the elderly population with comorbidities, has been increasing. In addition, the length of hospital stay and total medical costs of the CDI group were greater than those of the control group.

A survey of current practices in post-polypectomy surveillance in Korea.

BACKGROUND/AIMS: We investigated the clinical practice patterns of post-polypectomy colonoscopic surveillance among Korean endoscopists. METHODS: In a web-based survey conducted between September and November 2021, participants were asked about their preferred surveillance intervals and the patient age at which surveillance was discontinued. Adherence to the recent guidelines of the U.S. Multi-Society Task Force on Colorectal Cancer (USMSTF) was also analyzed. RESULTS: In total, 196 endoscopists completed the survey. The most preferred first surveillance intervals were: a 5-year interval after the removal of 1-2 tubular adenomas < 10 mm; a 3-year interval after the removal of 3-10 tubular adenomas < 10 mm, adenomas ≥ 10 mm, tubulovillous or villous adenomas, ≤ 20 hyperplastic polyps < 10 mm, 1-4 sessile serrated lesions (SSLs) < 10 mm, hyperplastic polyps or SSLs ≥ 10 mm, and traditional serrated adenomas; and a 1-year interval after the removal of adenomas with highgrade dysplasia, >10 adenomas, 5-10 SSLs, and SSLs with dysplasia. In piecemeal resections of large polyps ( > 20 mm), surveillance colonoscopy was mostly preferred after 1 year for adenomas and 6 months for SSLs. The mean USMSTF guideline adherence rate was 30.7%. The largest proportion of respondents (40.8%-55.1%) discontinued the surveillance at the patient age of 80-84 years. CONCLUSIONS: A significant discrepancy was observed between the preferred post-polypectomy surveillance intervals and recent international guidelines. Individualized measures are required to increase adherence to the guidelines.