Using a Deep Learning Model to Address Interobserver Variability in the Evaluation of Ulcerative Colitis (UC) Severity.

The use of endoscopic images for the accurate assessment of ulcerative colitis (UC) severity is crucial to determining appropriate treatment. However, experts may interpret these images differently, leading to inconsistent diagnoses. This study aims to address the issue by introducing a standardization method based on deep learning. We collected 254 rectal endoscopic images from 115 patients with UC, and five experts in endoscopic image interpretation assigned classification labels based on the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) scoring system. Interobserver variance analysis of the five experts yielded an intraclass correlation coefficient of 0.8431 for UCEIS scores and a kappa coefficient of 0.4916 when the UCEIS scores were transformed into UC severity measures. To establish a consensus, we created a model that considered only the images and labels on which more than half of the experts agreed. This consensus model achieved an accuracy of 0.94 when tested with 50 images. Compared with models trained from individual expert labels, the consensus model demonstrated the most reliable prediction results.

Development of functional gastrointestinal disorder symptoms following laparoscopic cholecystectomy: a prospective cohort study.

Background: The casual relationship between the role of cholecystectomy and functional gastrointestinal disorders (FGIDs) are a controversial clinical challenge. This study aimed to investigate: (1) the overlap of FGIDs before cholecystectomy and its long-term outcome after surgery in patients with symptomatic cholelithiasis, and (2) the incidence of new-onset FGIDs after cholecystectomy. Methods: Patients with symptomatic gallstone disease who underwent elective, laparoscopic cholecystectomy were prospectively enrolled. Healthy populations who underwent medical check-ups were selected as age- and sex-matched controls. Questionnaires regarding sociodemographic characteristics, gastrointestinal symptoms and a somatization symptom checklist (SSC) were completed at baseline and 12 months thereafter. Results: The prevalence of all FGID symptoms before cholecystectomy were significantly higher in the group of patients with symptomatic cholecystolithiasis compared to the control group. In cholecystectomy group, the preoperative FGID symptoms improved after surgery, except for chronic diarrhea. Compared to the controls, the new-onset FGIDs, including functional dyspepsia (14.8% vs. 6.9%; p = 0.040), functional diarrhea (6.6% vs. 0.2%; p < 0.001), and chronic abdominal pain (11.9% vs. 4.4%; p = 0.024), were more common at 1 year after cholecystectomy. Somatization was independent predictors of new-onset dyspepsia and abdominal pain, while newly occurring diarrhea was not realted to somatization. Conclusion: Overlap of FGIDs was common in patients with symptomatic cholelithiasis before surgery and at follow-up 1 year after cholecystectomy. Furthermore, new-onset FGIDs could be occurred after cholecystectomy. Therefore, a delicate diagnostic approaches and appropriate treatments about co-existent FGIDs should be given in patients with cholelithiasis before and after cholecystectomy.

Effect of aging on the formation and growth of colonic epithelial organoids by changes in cell cycle arrest through TGF-ß-Smad3 signaling.

BACKGROUND: This study aimed to investigate how aging alters the homeostasis of the colonic intestinal epithelium and regeneration after tissue injury using organoid models and to identify its underlying molecular mechanism. METHODS: To investigate aging-related changes in the colonic intestinal epithelium, we conducted organoid cultures from old (older than 80 weeks) and young (6-10 weeks) mice and compared the number and size of organoids at day 5 of passage 0 and the growth rate of organoids between the two groups. RESULTS: The number and size of organoids from old mice was significantly lower than that from young mice (p < 0.0001) at day 5 of passage 0. The growth rate of old-mouse organoids from day 4 to 5 of passage 0 was significantly slower than that of young-mouse organoids (2.21 times vs. 1.16 times, p < 0.001). RNA sequencing showed that TGF-ß- and cell cycle-associated genes were associated with the aging effect. With regard to mRNA and protein levels, Smad3 and p-Smad3 in the old-mouse organoids were markedly increased compared with those in the young-mouse organoids. Decreased expression of ID1, increased expression of p16INK4a, and increased cell cycle arrest were observed in the old mouse-organoids. Treatment with SB431542, a type I TGF-ß receptor inhibitor, significantly increased the formation and growth of old-mouse organoids, and TGF-ß1 treatment markedly suppressed the formation of young-mouse organoids. In the acute dextran sulfate sodium-colitis model and its organoid experiments, the colonic epithelial regeneration after tissue injury in old mice was significantly decreased compared with young mice. CONCLUSIONS: Aging reduced the formation ability and growth rate of colonic epithelial organoids by increasing cell cycle arrest through TGF-ß-Smad3-p16INK4a signaling.

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.

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.

Rehabilitation Program for Improved Musculoskeletal Pain in Gastrointestinal Endoscopists: Multicenter Prospective Cohort Study.

Background/Aims: This study aimed to develop a rehabilitation program for musculoskeletal pain experienced by gastrointestinal endoscopists and to investigate its usefulness. Methods: This was a multicenter cohort study. During the first 2 weeks, a questionnaire regarding daily workload and musculoskeletal symptoms was administered. Then, a rehabilitation program including equipment/posture correction and stretching was conducted during the remaining 6 weeks. Follow-up daily workload and musculoskeletal symptom surveys were distributed during the last 2 weeks. The program satisfaction survey was performed at the 6th and 8th weeks. Results: Among 118 participants (69 men), 94% (n=111) complained of musculoskeletal pain at baseline. Various hospital activities at baseline were associated with multisite musculoskeletal pain, whereas only a few workloads were correlated with musculoskeletal pain after the rehabilitation program. Follow-up musculoskeletal pain was negatively correlated with equipment/posture program performance; arm/elbow pain was negatively correlated with elbow (R=-0.307) and wrist (R=-0.205) posture; leg/foot pain was negatively correlated with monitor position, shoulder, elbow, wrist, leg, and foot posture. Higher performance in the scope position (86.8% in the improvement vs 71.3% in the aggravation group, p=0.054) and table height (94.1% vs 79.1%, p=0.054) were associated with pain improvement. An increased number of colonoscopy procedures (6.27 in the aggravation vs 0.02 in the improvement group, p=0.017) was associated with pain aggravation. Most participants reported being average (32%) or satisfied (67%) with the program at the end of the study. Conclusions: Our rehabilitation program is easily applicable, satisfactory, and helpful for improving the musculoskeletal pain experienced by gastrointestinal endoscopists.

A Case of Intramural Gastric Wall Abscess, a Rare Disease Successfully Treated with Endoscopic Incision and Drainage.

Gastric wall abscess is a rare condition characterized by a purulent inflammatory process resulting in the formation of a pocket of pus in the stomach. As the mucosa is usually intact, it requires various tools such as endoscopic ultrasonography or computed tomography for the differential diagnosis to rule out more common subepithelial tumors. Even after the diagnosis, the treatment for gastric wall abscess was previously restricted to surgical resection in combination with antibiotics. Currently, in order to avoid unnecessary surgery, the alternative method of initial treatment with an endoscopic approach is recommended. It also helps to choose appropriate antibiotics with confirmation of the pathogen by drainage. There are few reports that describe the detailed processing of the endoscopic drainage, and there is no consensus on the treatment. The pathogens that cause gastric wall abscess are usually Streptococci, Staphylococci, and Escherichia coli. There is only one case reported to be caused by Candida albicans. This is the first report of Elizabethkingia anopheles as the pathogen of the gastric wall abscess. Here, we report a case of gastric wall abscess in a 75-year-old man, safely treated by endoscopic drainage and antibiotics, confirmed by isolating the contents of the abscess.

Compositional changes in fecal microbiota associated with clinical phenotypes and prognosis in Korean patients with inflammatory bowel disease.

BACKGROUND/AIMS: The fecal microbiota of Korean patients with inflammatory bowel disease (IBD) was investigated with respect to disease phenotypes and taxonomic biomarkers for diagnosis and prognosis of IBD. METHODS: Fecal samples from 70 ulcerative colitis (UC) patients, 39 Crohn's disease (CD) patients, and 100 healthy control individuals (HC) were collected. The fecal samples were amplified via polymerase chain reaction and sequenced using Illumina MiSeq. The relationships between fecal bacteria and clinical phenotypes were analyzed using the EzBioCloud database and 16S microbiome pipeline. RESULTS: The alpha-diversity of fecal bacteria was significantly lower in UC and CD (P<0.05) compared to that in HC. Bacterial community compositions in UC and CD were significantly different from that of HC according to Bray-Curtis dissimilarities, and there was also a difference between community composition in UC and CD (P=0.01). In UC, alpha-diversity was further decreased when the disease was more severe and the extent of disease was greater, and community composition significantly differed depending on the extent of the disease. We identified 9 biomarkers of severity and 6 biomarkers of the extent of UC. We also identified 5 biomarkers of active disease and 3 biomarkers of ileocolonic involvement in CD. Lachnospiraceae and Ruminococcus gnavus were biomarkers for better prognosis in CD. CONCLUSIONS: The fecal microbiota profiles of IBD patients were different from those of HC, and several bacterial taxa may be used as biomarkers to determine disease phenotypes and prognosis. These data may also help discover new therapeutic targets for IBD.

Clinical outcomes of acute upper gastrointestinal bleeding according to the risk indicated by Glasgow-Blatchford risk score-computed tomography score in the emergency room.

BACKGROUND/AIMS: Acute upper gastrointestinal (UGI) bleeding is a significant emergency situation with a mortality rate of 2% to 10%. Therefore, initial risk stratification is important for proper management. We aimed to evaluate the role of contrast-enhanced multidetector computed tomography (MDCT) for risk stratification in patients with acute UGI bleeding in the emergency room (ER). METHODS: This retrospective study included patients with UGI bleeding in the ER. Glasgow-Blatchford risk score-computed tomography (GBS-CT) was assessed using a combination of GBS and the MDCT scan scoring system. RESULTS: Of the 297 patients with UGI bleeding, 124 (41.8%) underwent abdominal MDCT. Among them, 90.3% were classified as high-risk by GBS, and five patients died (4.0%). Rebleeding occurred in nine patients (7.3%). The high-risk GBS-CT group had significantly higher in-hospital mortality (10.5% in high-risk vs. 1.4% in moderate risk vs. 0% in low-risk, p = 0.049), transfusion amount (p < 0.001), and endoscopic hemostasis (p < 0.001) compared to the moderate- and low-risk groups. CONCLUSION: Adding MDCT scans to the existing validated prognosis model when predicting the risk of UGI bleeding in patients in the ER plays a significant role in determining in-hospital mortality, transfusions, and the need for endoscopic hemostasis.

Long-term prognosis of curative endoscopic submucosal dissection for early colorectal cancer according to submucosal invasion: a multicenter cohort study.

BACKGROUND: Endoscopic submucosal dissection (ESD) can provide a high en bloc resection rate and has been widely applied as curative treatment for early colorectal cancer (ECC). However, surgical treatment is occasionally required, and reports on the long-term prognosis of ESD are insufficient. This study aimed to investigate the long-term outcomes of ECC removal by ESD, including local recurrence and metastasis. METHODS: This multicenter study was conducted retrospectively on 450 consecutive patients with ECC who were treated with ESD between November 2003 and December 2013. Clinical, pathological, and endoscopic data were collected to determine tumor depth, resection margin, lymphovascular invasion, and recurrence. RESULTS: The median follow-up period was 53.8 (12-138 months). The en bloc resection rate was 85.3% (384) and in intramucosal cancer being 84.1% and in superficial submucosal invasion (SM1) cancer being 89.8% (p = 0.158). The curative resection rate was 76.0% (n = 342), and there was no statistical difference between the two groups (77.3% vs. 71.4%, p = 0.231). The overall recurrence free survival rate (RFS) was 98.7% (444/450). In patients with curative resection, there was no statistically significant difference in RFS according to invasion depth (intramucosal: 99.3% vs. SM1: 97.1%, p = 0.248). CONCLUSIONS: Patients with curatively resected ECC treated with ESD showed favorable long-term outcomes. Curatively resected SM1 cancer has a RFS similar to that of intramucosal cancer.

Perspectives of East Asian patients and physicians on complementary and alternative medicine use for inflammatory bowel disease: results of a cross-sectional, multinational study.

BACKGROUND/AIMS: Complementary and alternative medicine (CAM) is prevalent in East Asia. However, information on CAM in East Asian patients with inflammatory bowel disease (IBD) is scarce. We aimed to profile the prevalence and pattern of CAM use among East Asian IBD patients and to identify factors associated with CAM use. We also compared physicians' perspectives on CAM. METHODS: Patients with IBD from China, Japan, and South Korea were invited to complete questionnaires on CAM use. Patient demographic and clinical data were collected. Logistic regression analysis was applied for predictors of CAM use. Physicians from each country were asked about their opinion on CAM services or products. RESULTS: Overall, 905 patients with IBD participated in this study (China 232, Japan 255, and South Korea 418). Approximately 8.6% of patients with IBD used CAM services for their disease, while 29.7% of patients sought at least 1 kind of CAM product. Current active disease and Chinese or South Korean nationality over Japanese were independent predictors of CAM use. Chinese doctors were more likely to consider CAM helpful for patients with IBD than were Japanese and South Korean doctors. CONCLUSIONS: In 8.6% and 29.7% of East Asian patients with IBD used CAM services and products, respectively, which does not differ from the prevalence in their Western counterparts. There is a significant gap regarding CAM usage among different Asian countries, not only from the patients' perspective but also from the physicians' point of view.

Suppressive effect of α-mangostin for cancer stem cells in colorectal cancer via the Notch pathway.

BACKGROUND: Since colon cancer stem cells (CSCs) play an important role in chemoresistance and in tumor recurrence and metastasis, targeting of CSCs has emerged as a sophisticated strategy for cancer therapy. α-mangostin (αM) has been confirmed to have antiproliferative and apoptotic effects on cancer cells. This study aimed to evaluate the selective inhibition of αM on CSCs in colorectal cancer (CRC) and the suppressive effect on 5-fluorouracil (5-FU)-induced CSCs. METHODS: The cell viability assay was performed to determine the optimal concentration of αM. A sphere forming assay and flow cytometry with CSC markers were carried out to evaluate the αM-mediated inhibition of CSCs. Western blot analysis and quantitative real-time PCR were performed to investigate the effects of αM on the Notch signaling pathway and colon CSCs. The in vivo anticancer efficacy of αM in combination with 5-FU was investigated using a xenograft mouse model. RESULTS: αM inhibited the cell viability and reduced the number of spheres in HT29 and SW620 cells. αM treatment decreased CSCs and suppressed the 5-FU-induced an increase in CSCs on flow cytometry. αM markedly suppressed Notch1, NICD1, and Hes1 in the Notch signaling pathway in a time- and dose-dependent manner. Moreover, αM attenuated CSC markers CD44 and CD133, in a manner similar to that upon DAPT treatment, in HT29 cells. In xenograft mice, the tumor and CSC makers were suppressed in the αM group and in the αM group with 5-FU treatment. CONCLUSION: This study shows that low-dose αM inhibits CSCs in CRC and suppresses 5-FU-induced augmentation of CSCs via the Notch signaling pathway.

Clinical Features and Long-term Prognosis of Crohn's Disease in Korea: Results from the Prospective CONNECT Study.

Background/Aims: The prospective Crohn's Disease Clinical Network and Cohort Study is a nationwide multicenter cohort study of patients with Crohn's disease (CD) in Korea, aiming to prospectively investigate the clinical features and long-term prognosis associated with CD. Methods: Patients diagnosed with CD between January 2009 and September 2019 were prospectively enrolled. They were divided into two cohorts according to the year of diagnosis: cohort 1 (diagnosed between 2009 and 2011) versus cohort 2 (between 2012 and 2019). Results: A total of 1,175 patients were included, and the median follow-up duration was 68 months (interquartile range, 39.0 to 91.0 months). The treatment-free durations for thiopurines (p<0.001) and anti-tumor necrosis factor agents (p=0.018) of cohort 2 were shorter than those of cohort 1. Among 887 patients with B1 behavior at diagnosis, 149 patients (16.8%) progressed to either B2 or B3 behavior during follow-up. Early use of thiopurine was associated with a reduced risk of behavioral progression (adjusted hazard ratio [aHR], 0.69; 95% confidence interval [CI], 0.50 to 0.90), and family history of inflammatory bowel disease was associated with an increased risk of behavioral progression (aHR, 2.29; 95% CI, 1.16 to 4.50). One hundred forty-one patients (12.0%) underwent intestinal resection, and the intestinal resection-free survival time was significantly longer in cohort 2 than in cohort 1 (p=0.003). The early use of thiopurines (aHR, 0.35; 95% CI, 0.23 to 0.51) was independently associated with a reduced risk of intestinal resection. Conclusions: The prognosis of CD in Korea appears to have improved over time, as evidenced by the decreasing intestinal resection rate. Early use of thiopurines was associated with an improved prognosis represented by a reduced risk of intestinal resection.

Efficacy and safety of split-dose bowel preparation with 1 L polyethylene glycol and ascorbate compared with 2 L polyethylene glycol and ascorbate in a Korean population: a phase IV, multicenter, randomized, endoscopist-blinded study.

BACKGROUND AND AIMS: The 1-L polyethylene glycol (PEG)-based bowel preparation agent NER1006 (Plenvu; Norgine, Harefield, UK) has shown high cleansing efficacy and tolerability in clinical trials in Europe and North America. However, no clinical trials have yet been reported in Asia. Therefore, the aim of this study was to evaluate the efficacy and safety of 1L PEG-based bowel preparation with Plenvu compared with 2L PEG plus ascorbate bowel preparation in a Korean population. METHODS: In this multicenter, endoscopist-blinded, randomized study, patients at 9 hospitals in South Korea undergoing colonoscopy received either Plenvu or 2L PEG + ascorbate (2L PEG) with a split dose. The primary endpoint was overall bowel cleansing success (Boston Bowel Preparation Scale [BBPS] score ≥2 for all segments of the colon). Secondary endpoints were high-quality bowel cleansing success (overall, BBPS score = 9; segmental colon, BPPS score = 3), polyp detection rate (PDR), and adenoma detection rate (ADR). RESULTS: Of 360 included patients, cleansing efficacy was analyzed in 346 (Plenvu, 174; 2L PEG, 172). The Plenvu group showed noninferior bowel cleansing success rates compared with 2L PEG (93.10% vs 91.86%; difference, 1.24%; 1-sided 97.5% lower confidence limit, -4.31%; Pnoninferiority < .0001; Psuperiority = .661). The Plenvu group had higher high-quality bowel cleansing success rates for overall and right-sided colon segments than the 2L PEG group (49.43% vs 37.79% [P = .029] and 60.92% vs 48.84% [P = .024], respectively). The PDR was greater with Plenvu than with 2L PEG (48.85% vs 37.79%, P = .038). However, ADR did not differ between the 2 groups (24.71% vs 20.35%, P = .331). Although treatment-emergent adverse events (TEAEs) were slightly higher in the Plenvu group than in the 2L PEG group (65.71% vs 52.91%, P = .015), most TEAEs were mild (85.55%) and most patients recovered without any management (99.23%). CONCLUSIONS: Plenvu showed noninferior overall bowel cleansing success rates comparable with 2L PEG but greater high-quality bowel cleansing in overall and right-sided colon, which might help improve the PDR in the Asian population. (Clinical trial registration number: KCT0005894.).

Fasting Blood Glucose Variability and Unfavorable Trajectory Patterns Are Associated with the Risk of Colorectal Cancer.

Background/Aims: The relationship between fasting blood glucose (FBG) variability and colorectal cancer (CRC) remains ill-defined. This study aimed to evaluate the association of FBG variability with CRC risk in the healthy population without overt diabetes. Methods: In the data from the Korean National Health Insurance Service-Health Screening Cohort, we included individuals examined by FBG testing at least 3 times between 2002 and 2007. FBG variability was calculated using standard deviation (SD) and coefficient of variation (CV). Results: Regarding FBG variability, an increase in the quintile of SD or CV was independently associated with CRC risk (all p for trend <0.01). When the change in FBG was classified into six trajectory patterns, unfavorable trajectory patterns (high stable and upward) were significantly associated with increased CRC risk (hazard ratio [HR] 2.30, p=0.003; HR 1.19, p=0.007, respectively). In subgroup analyses according to the sex, a significant association between FBG variability (SD or CV) and CRC risk was observed in men but not in women. The high stable and upward pattern were also associated with CRC risk in men (HR 2.47, p=0.002; HR 1.21, p=0.012) but not in women. Conclusions: This study identified that FBG variability and unfavorable trajectory patterns were significantly associated with increased CRC risk in the healthy population without overt diabetes. Our findings suggest that FBG variability as well as FBG itself may be a predictive factor for the development of CRC.

Clinical outcomes and predictors of response for adalimumab in patients with moderately to severely active ulcerative colitis: a KASID prospective multicenter cohort study.

BACKGROUND/AIMS: This study assessed the efficacy and safety of adalimumab (ADA) and explored predictors of response in Korean patients with ulcerative colitis (UC). METHODS: A prospective, observational, multicenter study was conducted over 56 weeks in adult patients with moderately to severely active UC who received ADA. Clinical response, remission, and mucosal healing were assessed using the Mayo score. RESULTS: A total of 146 patients were enrolled from 17 academic hospitals. Clinical response rates were 52.1% and 37.7% and clinical remission rates were 24.0% and 22.0% at weeks 8 and 56, respectively. Mucosal healing rates were 39.0% and 30.1% at weeks 8 and 56, respectively. Prior use of anti-tumor necrosis factor-α (anti-TNF-α) did not affect clinical and endoscopic responses. The ADA drug level was significantly higher in patients with better outcomes at week 8 (P<0.05). In patients with lower endoscopic activity, higher body mass index, and higher serum albumin levels at baseline, the clinical response rate was higher at week 8. In patients with lower Mayo scores and C-reactive protein levels, clinical responses, and mucosal healing at week 8, the clinical response rate was higher at week 56. Serious adverse drug reactions were identified in 2.8% of patients. CONCLUSIONS: ADA is effective and safe for induction and maintenance in Korean patients with UC, regardless of prior anti-TNF-α therapy. The ADA drug level is associated with the efficacy of induction therapy. Patients with better short-term outcomes were predictive of those with an improved long-term response.

Efficacy and Safety of TJP-008 Compared to 2 L PEG with Ascorbate in Colon Cleansing: A Randomized Phase 3 Trial.

BACKGROUND/AIMS: Polyethylene glycol (PEG)-based bowel preparations are effective cleansing agents for colonoscopy. However, they require relatively large volumes to be used even with agents such as 2 L PEG with ascorbate (2LPEG). This phase 3, randomized, single-blinded, multicenter, parallel-group study compared the efficacy of 1 L PEG with high-dose ascorbate, TJP-008, to 2LPEG. METHODS: Patients undergoing colonoscopy were randomized (1:1:1) to receive TJP-008 as 1-day split dose (TJP-008-1) or 2-day split dose (TJP-008-2) regimen or to receive 2LPEG as a 2-day split dose regimen. Cleansing efficacy was evaluated using the Harefield Cleansing Scale. The primary endpoint was overall bowel cleansing success. Full analysis set (FAS) and per protocol set (PPS) analyses were performed. RESULTS: Of the 314 screened patients, efficacy was assessed in the following patient numbers (FAS/PPS): total (293/285), TJP-008-1 (98/94), TJP-008-2 (97/95), and 2LPEG (98/96). FAS revealed noninferiority between TJP-008 and 2LPEG with regard to overall success (TJP-008-2, 99.0%; TJP-008-1, 95.9%; 2LPEG, 94.9%; p=0.100 and p=0.733, respectively). PPS also showed noninferiority (p=0.721 and p=0.211, respectively). However, the PPS analyses showed a higher bowel cleansing score for TJP-008-2 for high-quality cleansing in the right colon (TJP-008-2 83.2% vs 2LPEG 62.5%; p=0.005). CONCLUSIONS: TJP-008 is a new low-volume cleansing agent with a colon cleansing efficacy comparable to that of standard 2LPEG that exhibits significant safety and tolerability.

Clinical Course of COVID-19 in Patients with Inflammatory Bowel Disease in Korea: a KASID Multicenter Study.

In 2020, the novel coronavirus disease 2019 (COVID-19) began to spread worldwide and remains an ongoing medical challenge. This case series reports on the clinical features and characteristics of patients with inflammatory bowel disease (IBD) and confirmed COVID-19 infection. From February 2020 to March 2021, nine patients with IBD had confirmed COVID-19 across four hospitals in Korea. The median age at COVID-19 diagnosis was 42 years. Six patients were male, and seven patients had ulcerative colitis (UC). No patients required oxygen therapy, intensive care unit hospitalizations, or died. The most common symptom was fever, and gastrointestinal (GI) symptoms developed as diarrhea in five patients with UC. Oral steroids were used to combat UC aggravation in two patients. In this case series of nine IBD patients diagnosed with COVID-19 in Korea, the clinical presentation was predominately a mild respiratory tract infection. Most patients with UC developed new GI symptoms including diarrhea.

Three-dimensional culture method enhances the therapeutic efficacies of tonsil-derived mesenchymal stem cells in murine chronic colitis model.

Tonsil-derived mesenchymal stem cells (TMSCs) showed therapeutic effects on acute and chronic murine colitis models, owing to their immunomodulatory properties; therefore, we evaluated enhanced therapeutic effects of TMSCs on a murine colitis model using three-dimensional (3D) culture method. The expression of angiogenic factors, VEGF, and anti-inflammatory cytokines, IL-10, TSG-6, TGF-ß, and IDO-1, was significantly higher in the 3D-TMSC-treated group than in the 2D-TMSC-treated group (P < 0.05). At days 18 and 30 after inducing chronic colitis, disease activity index scores were estimated to be significantly lower in the 3D-TMSC-treated group than in the colitis control (P < 0.001 and P < 0.001, respectively) and 2D-TMSC-treated groups (P = 0.022 and P = 0.004, respectively). Body weight loss was significantly lower in the 3D-TMSC-treated group than in the colitis control (P < 0.001) and 2D-TMSC-treated groups (P = 0.005). Colon length shortening was significantly recovered in the 3D-TMSC-treated group compared to that in the 2D-TMSC-treated group (P = 0.001). Histological scoring index was significantly lower in the 3D-TMSC-treated group than in the 2D-TMSC-treated group (P = 0.002). These results indicate that 3D-cultured TMSCs showed considerably higher therapeutic effects in a chronic murine colitis model than those of 2D-cultured TMSCs via increased anti-inflammatory cytokine expression.

Cost-Effectiveness, Efficacy, and Safety Analysis of Tailored Therapy in Patients with Helicobacter pylori Infection.

Recently in Korea, where triple therapy is accepted as the first-line Helicobacter pylori (H. pylori) eradication treatment, antibiotic resistance to clarithromycin has increased considerably, resulting in eradication rates of less than 80%. We investigated the efficacy of tailored therapy after a clarithromycin resistance test compared with empirical therapy for H. pylori eradication. The cost-effectiveness of H. pylori eradication success was evaluated according to the average medical cost per patient. A total of 364 patients were enrolled in the study. The first-line H. pylori eradication rate was significantly higher in patients who received tailored therapy than in those who received empirical therapy. The total medical costs for the tailored and empirical groups were 46,374 Won and 53,528 Won. The total treatment period for each ultimately successful eradication in the tailored group was 79.8 ± 2.8 days, which is shorter than that of the empirical group (99.2 ± 7.4 days). The rate of eradication-related adverse events for the tailored group and empirical group was 12.9% and 14.8%, respectively. Tailored therapy could be a useful option to achieve a higher successful eradication rate, shorter treatment periods, and lower medical costs than empirical therapy in the era of increasing antibiotic resistance.