Self-screening questionnaire for perianal fistulizing disease in patients with Crohn's disease.

BACKGROUND/AIMS: A poor prognostic factor for Crohn's disease (CD) includes perianal fistulizing disease, including perianal fistula and/or perianal abscess. Currently, a tool to assess perianal symptoms in patients with CD remains nonexistent. This study aimed to develop a perianal fistulizing disease self-screening questionnaire for patients with CD. METHODS: This prospective pilot study was conducted at three tertiary referral centers between January 2019 and May 2020. We formulated questions on perianal symptoms, including tenesmus, anal discharge, bleeding, pain, and heat. A 4-point Likert scale was used to rate each question. Patients with CD completed a questionnaire and underwent pelvic magnetic resonance imaging (MRI). RESULTS: Overall, 93 patients were enrolled, with 51 (54.8%) diagnosed with perianal fistulizing disease, as determined by pelvic MRI. The Spearman correlation findings demonstrated that anal pain (p = 0.450, p < 0.001) and anal discharge (p = 0.556, p < 0.001) were the symptoms that most significantly correlated with perianal disease. For anal pain and discharge, the area under the receiver operating characteristic curve of the scores was significantly higher than that of the combined score for all five symptoms (0.855 vs. 0.794, DeLong's test p = 0.04). For the two symptoms combined, the sensitivity, specificity, and positive predictive and negative predictive values were 88.2, 73.8, 80.4, and 83.8%, respectively, with 81.7% accuracy for detecting perianal fistulizing disease. CONCLUSION: This study indicates that simple questions regarding anal pain and discharge can help accurately identify the presence of perianal fistulizing disease in patients with CD.

Mobile monitoring system detects the disease activity pattern and shows the association with clinical outcomes in patients with newly diagnosed Crohn's disease.

We aimed to determine whether Crohn's disease (CD) activity patterns assessed via a web-based symptom diary can help predict clinical outcomes in patients with newly diagnosed CD. Patients diagnosed with CD within the preceding 3 months were prospectively enrolled at four tertiary centers. All patients recorded their symptoms on a website using a smartphone at least once a week. The index outcomes were disease-related admission and surgery during follow-up. The disease activity from enrollment to outcome or last follow-up was reviewed for pattern analysis. Cox regression analysis was used to identify the predictors of disease outcomes. A total of 102 patients were enrolled. During a median follow-up period of 42 months, 25 (24.5%) and 6 (5.9%) patients required admission and surgery, respectively. Poor activity pattern was an independent predictor of disease-related hospitalization (adjusted hazard ratio [aHR], 3.96; 95% confidence interval [CI] 1.5-10.45; p = 0.005). A poor activity pattern (aHR, 19.48; 95% CI 1.86-203.95; p = 0.013) and female sex (aHR, 11.28; 95% CI 1.49-85.01; p = 0.018) were found to be independent predictors of bowel resection. CD disease activity patterns monitored through the mobile monitoring system may help predict clinical outcomes, such as disease-related hospitalization and surgery, in patients with newly diagnosed CD.

Efficacy and safety of CKD-495 in acute and chronic gastritis: A Phase III superiority clinical trial.

BACKGROUND: Despite the availability of numerous treatment options, many patients with gastritis experience only partial symptom relief. CKD-495, a newly developed product with the active ingredient extracted from Cinnamomum cassia Presl., has demonstrated anti-inflammatory and antioxidant activity in vitro and an in vivo protective effect against gastric damage by stimulating mucus secretion. This study compared the efficacy and safety of CKD-495 with Artemisiae argyi folium (AAF) for the treatment of acute and chronic gastritis. AAF, a gastric mucosa protective agent that promotes gastric mucosa regeneration, has been used clinically for about 20 years. METHODS: This phase III multicenter, randomized, double-blind, parallel-group trial (ClinicalTrials.gov; NCT04255589) assigned 242 patients with endoscopically-proven gastric mucosal erosions to receive CKD-495 75 mg (n = 122) or AAF 60 mg (n = 120), respectively, with placebo (for double-blind purposes) 3 times a day for 2 weeks. The primary efficacy endpoint was the erosion improvement rate. Secondary endpoints included erosion cure rates, and improvement rates for edema, redness, hemorrhage, and gastrointestinal (GI) symptoms. Drug-related adverse events were evaluated. RESULTS: The erosion improvement rate was significantly higher in the CKD-495 group than in the AAF group for both the full analysis set (55.9% vs 39.4%, P = .0063) and per-protocol set (54.6% vs 38.2%, P = .0084). In addition, the erosion improvement rate in patients with acute or chronic gastritis showed that the CKD-495 group had better improvement of erosion than the AAF group, especially in patients with chronic gastritis. Analysis of secondary endpoints, which included erosion cure rate and the improvement rates of edema, redness, hemorrhage, and GI symptoms, showed that the CKD-495 group was more effective than the AAF group. There were no significant between-group differences in safety profiles. No serious adverse events or adverse drug reactions occurred. CONCLUSIONS: These results demonstrate that CKD-495 75 mg is superior to AAF 60 mg in terms of the endoscopic improvement rate of erosions in patients with acute or chronic gastritis. This new mucoprotective agent, CKD-495, can be considered the therapy of choice for symptomatic relief and healing of gastritis.

Effectiveness and safety of adalimumab in patients with intestinal Behçet's disease: a real-world prospective observational study in South Korea.

BACKGROUND: Intestinal Behçet's disease (BD) is characterized by typical gastrointestinal ulcers in patients with BD followed by complications such as bleeding, perforation and fistula. Biologic agents are currently under active investigation to delay the disease course. Various data regarding infliximab are available, but there is relatively lack of data regarding adalimumab. METHODS: This was a multicenter, real-world prospective observational study to evaluate the effectiveness and safety of adalimumab in intestinal BD. The primary endpoint was disease activity at each follow up, including disease activity index for intestinal Behçet's disease (DAIBD), serum C-reactive protein (CRP) level, and endoscopic findings. The secondary endpoint was the incidence of adverse drug reactions (ADRs). RESULTS: A total of 58 patients were enrolled and 8 of them were excluded. Adverse events were reported in 72.0% of patients with 122 events. ADRs were reported in 24.0% with 28 events. For adverse events, arthralgia was most commonly reported (13.1%: 16/122) and only one experienced critical adverse event (0.82%, 1/122: death due to stroke). On multivariable regression analysis, a longer disease duration was significantly associated with decreased ADRs [Odds ratio 0.976 (0.953-0.999, 95% CI); p = 0.042]. Clinical response rates as assessed by DAIBD were 90.9% at Week 12 and 89.7% at Week 56, respectively. The mean serum CRP level at baseline was significantly decreased after 12 weeks (3.91 ± 4.93 to 1.26 ± 2.03 mg/dL; p = 0.0002). CONCLUSION: Adalimumab was found to be safe and effective in Korean patients with intestinal BD. A longer disease duration was significantly associated with decreased ADRs.

Efficacy and safety of 1 L polyethylene glycol plus ascorbic acid for bowel preparation in elderly: comparison with oral sulfate solution.

BACKGROUND/AIMS: Recently, 1 L of polyethylene glycol (PEG) plus ascorbic acid (Asc) has been introduced in Korea as a colonoscopy preparation agent. Data on its efficacy and safety in older adults have been limited. We aimed to evaluate the safety and efficacy of 1 L PEG/Asc in older adults by comparing it with oral sulfate solution (OSS). METHODS: A prospective multicenter randomized study was conducted with subjects aged ≥ 65 years who underwent colonoscopy. The participants were randomized to receive 1 L PEG/Asc or OSS. The primary endpoint was successful bowel preparation, defined as total Boston Bowel Preparation Scale ≥ 6, and ≥ 2 at each segment. Patient satisfaction, adverse events, and renal function changes were compared between the groups. RESULTS: Among the 106 patients, 104 were finally included in the analysis. Overall, successful bowel preparation was achieved in 96.2% of both 1 L PEG/Asc and OSS groups. The satisfaction scores for taste, total amount ingested, overall feeling, and willingness to repeat the same regimen were not significantly different between the groups. Adverse events of moderate or higher severity occurred in 16 and 10 cases in the 1 L PEG/Asc and OSS group, respectively. There were no significant changes in electrolyte levels or renal function from baseline. CONCLUSION: The successful bowel preparation rate was > 90% in both groups without severe adverse effects and significant changes in renal function. As a new low-dose preparation regimen for colonoscopy in older adults, 1 L PEG/Asc, is as effective and safe as OSS.

Incidence of colonoscopy-related perforation and risk factors for poor outcomes: 3-year results from a prospective, multicenter registry (with videos).

BACKGROUND AND AIMS: Perforation is a life-threatening adverse event of colonoscopy that often requires hospitalization and surgery. We aimed to prospectively assess the incidence of colonoscopy-related perforation in a multicenter registry and to analyze the clinical factors associated with poor clinical outcomes. METHODS: This prospective observational study was conducted at six tertiary referral hospitals between 2017 and 2020, and included patients with colonic perforation after colonoscopy. Poor clinical outcomes were defined as mortality, surgery, and prolonged hospitalization (> 13 days). Logistic regression was used to identify factors associated with poor clinical outcomes. RESULTS: Among 84,673 patients undergoing colonoscopy, 56 had colon perforation (0.66/1000, 95% confidence interval [CI] 0.51-0.86). Perforation occurred in 12 of 63,602 diagnostic colonoscopies (0.19/1000, 95% CI 0.11-0.33) and 44 of 21,071 therapeutic colonoscopies (2.09/1000, 95% CI 1.55-2.81). Of these, 15 (26.8%) patients underwent surgery, and 25 (44.6%) patients had a prolonged hospital stay. One patient (1.8%) died after perforation from a diagnostic colonoscopy. In the multivariate analysis, diagnostic colonoscopy (adjusted odds ratio [aOR] 196.43, p = 0.025) and abdominal rebound tenderness (aOR 17.82, p = 0.012) were independent risk factors for surgical treatment. The location of the sigmoid colon (aOR 18.57, p = 0.048), delayed recognition (aOR 187.71, p = 0.008), and abdominal tenderness (aOR 63.20, p = 0.017) were independent risk factors for prolonged hospitalization. CONCLUSIONS: This prospective study demonstrated that the incidence of colonoscopy-related perforation was 0.66/1000. The incidence rate was higher in therapeutic colonoscopy, whereas the risk for undergoing surgery was higher in patients undergoing diagnostic colonoscopy. Colonoscopy indication (diagnostic vs. therapeutic), physical signs, the location of the sigmoid perforation, and delayed recognition were independent risk factors for poor clinical outcomes in colonoscopy-related perforation.

Efficacy and Safety of Fexuprazan in Patients with Acute or Chronic Gastritis.

Background/Aims: Fexuprazan is a novel potassium-competitive acid blocker that could be of benefit to patients with gastric mucosal injury. The aim of this study was to assess the 2-week efficacy and safety of fexuprazan in patients with acute or chronic gastritis. Methods: In this study, 327 patients with acute or chronic gastritis who had one or more gastric erosions on endoscopy and subjective symptoms were randomized into three groups receiving fexuprazan 20 mg once a day (q.d.), fexuprazan 10 mg twice a day (b.i.d.), or placebo for 2 weeks. The posttreatment assessments were the primary endpoint (erosion improvement rate), secondary endpoints (cure rates of erosion and edema and improvement rates of redness, hemorrhage, and subjective symptoms), and drug-related adverse events. Results: Among the patients, 57.8% (59/102), 65.7% (67/102), and 40.6% (39/96) showed erosion improvement 2 weeks after receiving fexuprazan 20 mg q.d., fexuprazan 10 mg b.i.d., and placebo, respectively. Both fexuprazan 20 mg q.d. and 10 mg b.i.d. showed superior efficacy to the placebo (p=0.017 and p<0.001, respectively). Likewise, both fexuprazan 20 mg q.d. and 10 mg b.i.d. also showed higher erosion healing rates than the placebo (p=0.033 and p=0.010, respectively). No difference was noted in the edema healing rate and the improvement rates for redness, hemorrhage, and subjective symptoms between the fexuprazan and placebo groups. No significant difference was noted in the incidence of adverse drug reactions. Conclusions: Fexuprazan 20 mg q.d. and 10 mg b.i.d. for 2 weeks showed therapeutic efficacy superior to that of placebo in patients with acute or chronic gastritis (ClinicalTrials.gov identifier NCT04341454).

Randomised clinical trial: comparison of tegoprazan and lansoprazole as maintenance therapy for healed mild erosive oesophagitis.

BACKGROUND: Tegoprazan is a novel potassium-competitive acid blocker used to treat acid-related disorders. AIM: To compare tegoprazan 25 mg with lansoprazole 15 mg as maintenance therapy in healed erosive oesophagitis (EE) METHODS: In this phase 3, double-blind, multi-centre study, patients with endoscopically confirmed healed EE were randomised 1:1 to receive tegoprazan 25 mg or lansoprazole 15 mg once daily for up to 24 weeks. The primary efficacy endpoint was the endoscopic remission rate after 24 weeks. The secondary efficacy endpoint was the endoscopic remission rate after 12 weeks. Safety endpoints included adverse events, clinical laboratory results and serum gastrin and pepsinogen I/II levels. RESULTS: We randomised patients to tegoprazan 25 mg (n = 174) or lansoprazole 15 mg (n = 177). Most had mild EE (Los Angeles (LA) grade A: 57.3%, LA grade B: 37.3%). The endoscopic remission rate after 24 weeks was 90.6% with tegoprazan and 89.5% with lansoprazole. Tegoprazan was not inferior to lansoprazole for maintaining endoscopic remission at 24 weeks and 12 weeks. In subgroup analysis, tegoprazan 25 mg showed no significant difference in maintenance rate according to LA grade (p = 0.47). The maintenance effect of tegoprazan was consistent in CYP2C19 extensive metabolisers (p = 0.76). Increases in serum gastrin were not higher in tegoprazan-treated than lansoprazole-treated patients. CONCLUSIONS: Tegoprazan 25 mg was non-inferior to lansoprazole 15 mg in maintenance of healing of mild EE. In this study, tegoprazan had a similar safety profile to lansoprazole.

Efficacy and Safety of Infliximab in Intestinal Behçet's Disease: A Multicenter, Phase 3 Study (BEGIN).

Background/Aims: To date, there is no prospective study that specifically investigated the efficacy of infliximab in intestinal Behçet's disease (BD). This study evaluated the efficacy of infliximab in patients with moderate-to-severe active intestinal BD that are refractory to conventional therapies. Methods: This phase 3, interventional, open-label, single-arm study evaluated clinical outcomes of infliximab treatment in patients with moderate-to-severe intestinal BD. The coprimary endpoints were clinical response, decrease in disease activity index for intestinal BD (DAIBD) score ≥20 from weeks 0 to 8 for the induction therapy and week 32 for the maintenance therapy. Results: A total of 33 patients entered the induction therapy and were treated with infliximab 5 mg/kg intravenously at weeks 0, 2, and 6. The mean DAIBD score changed from 90.8±40.1 at week 0 to 40.3±36.4 at week 8, with a significant mean change of 50.5±36.4 (95% confidence interval, 37.5 to 63.4; p<0.001). Thirty-one (93.9%) continued to receive 5 mg/kg infliximab every 8 weeks during the maintenance therapy. The mean change in the DAIBD score after the maintenance therapy was statistically significant (61.5±38.5; 95% confidence interval, 46.0 to 77.1; p<0.001, from weeks 0 to 32). The proportion of patients who maintained a clinical response was 92.3% at week 32. No severe adverse reactions occurred during the induction and maintenance therapies. Conclusions: This study provided evidence that infliximab 5 mg/kg induction and maintenance therapies are efficacious and well-tolerated in patients with moderate-to-severe active intestinal BD. (ClinicalTrials.gov identifier: NCT02505568).

Comparison of the Pharmacokinetics of CT-P13 Between Crohn's Disease and Ulcerative Colitis.

BACKGROUND: We aimed to compare trough infliximab levels and the development of antidrug antibody (ADA) for 1 year between Crohn's disease (CD) and ulcerative colitis (UC) patients who were biologic-naive, and to evaluate their impact on clinical outcomes. METHODS: This was a prospective, multicenter, observational study. Biologic-naive patients with moderate to severe CD or UC who started CT-P13, an infliximab biosimilar, therapy were enrolled. Trough drug and ADA levels were measured periodically for 1 year after CT-P13 initiation. RESULTS: A total of 267 patients who received CT-P13 treatment were included (CD 168, UC 99). The rates of clinical remission (72% vs. 32.3%, P <0.001) at week 54 were significantly higher in CD than in UC. The median trough drug level (µg/mL) was significantly higher in CD than in UC up to week 14 (week 2, 18.7 vs. 14.7, P <0.001; week 6, 12.5 vs. 8.6, P <0.001; week 14, 3.4 vs. 2.5, P =0.001). The median ADA level (AU/mL) was significantly lower in CD than in UC at week 2 (6.3 vs. 6.5, P =0.046), week 30 (7.9 vs. 11.8, P =0.007), and week 54 (9.3 vs. 12.3, P =0.032). Development of ADA at week 2 [adjusted odds ratio (aOR)=0.15, P =0.026], initial C-reactive protein level (aOR=0.87, P =0.032), and CD over UC (aOR=1.92, P <0.001) were independent predictors of clinical remission at week 54. CONCLUSION: Infliximab shows more favorable pharmacokinetics, including high drug trough and low ADA levels, in CD than in UC, which might result in better clinical outcomes for 1-year infliximab treatment in CD patients.

Randomized controlled trial to evaluate the efficacy and safety of fexuprazan compared with esomeprazole in erosive esophagitis.

BACKGROUND: Fexuprazan, a novel potassium-competitive acid blocker, reversibly suppresses the K+/H+-ATPase enzyme in proton pumps within gastric parietal cells. Fexuprazan's suppression of gastric acid was maintained in healthy individuals for 24 h in a dose-dependent manner. AIM: To compare fexuprazan to esomeprazole and establish its efficacy and safety in patients with erosive esophagitis (EE). METHODS: Korean adult patients with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg or esomeprazole 40 mg once daily for eight weeks. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy at week 8. The secondary endpoints included the healing rate of EE at week 4, symptom response, and quality of life assessment. Safety profiles and serum gastrin levels were compared between the groups. RESULTS: Of the 263 randomized, 218 completed the study per protocol (fexuprazan 40 mg, n = 107; esomeprazole 40 mg, n = 111). Fexuprazan was non-inferior to esomeprazole regarding the healing rate at week 8 [99.1% (106/107) vs 99.1% (110/111)]. There were no between-group differences in the EE healing rate at week 4 [90.3% (93/103) vs 88.5% (92/104)], symptom responses, and quality of life assessments. Additionally, serum gastrin levels at weeks 4 and 8 and drug-related side effects did not significantly differ between the groups. CONCLUSION: Fexuprazan 40 mg is non-inferior to esomeprazole 40 mg in EE healing at week 8. We suggest that fexuprazan is an alternative promising treatment option to PPIs for patients with EE.

Efficacy, safety and tolerability of oral sulphate tablet for bowel preparation in patients with inflammatory bowel disease: A multicentre randomized controlled study.

BACKGROUND AND AIMS: We evaluated the efficacy, safety and tolerability of novel oral sulphate tablets [OSTs] vs 2 L of polyethylene glycol and ascorbate [PEG/Asc] in patients with inflammatory bowel disease [IBD]. PATIENTS AND METHODS: A total of 110 patients with clinically inactive IBD were enrolled in this single-blind multicentre non-inferiority study. Patients were randomly assigned to the OST or 2 L PEG/Asc group and we applied a split-dose regimen. The primary efficacy endpoint was bowel cleansing success rate defined as Harefield Cleansing Scale Grade A or B. The secondary endpoints were perfect preparation rate, the presence of air bubbles, safety as assessed by laboratory abnormalities and self-reported adverse events, or IBD symptom flare-ups. Tolerability was assessed by a pre-procedural visual analog scale [VAS] interview. RESULTS: Both groups showed high cleansing success rates [98.1%] and there was no significant difference in perfect preparation rate. The proportion of a bubble score 0 was significantly higher in the OST group [94.5% vs 50.0%, p < 0.001]. There was no significant intergroup difference in vomiting or bloating. Symptom flare-ups occurred in two OST group patients. No clinically significant blood test abnormalities were noted in either group. Ease of ingestion and taste scores were significantly higher in the OST group. More patients in the OST group [94.5%] wanted to take the same preparation agent for their next colonoscopy. CONCLUSIONS: Both OST and 2 L PEG/Asc demonstrated high successful cleansing and safety in patients with inactive IBD. OST achieved higher satisfaction than 2 L PEG/Asc. Our results suggest that the OST split-dose regimen is effective and safe for patients with inactive IBD.

Improved Image Analysis for Measuring Gastric Ulcer Index in Animal Models and Clinical Diagnostic Data.

Gastric ulcers are one of the most common gastrointestinal diseases. In this study, as an attempt to reduce the minimal error in clinical observations during the diagnosis of gastric ulcers, the applicability of improved ImageJ analysis (IA) was investigated by comparing the results of animal experiments and clinical data. As a result, IA exhibited a significantly improved potential for determining the ulcer index (UI) of clinical data sheets compared to those rated directly by conventional clinical observation (CCO). This indicated that IA enhanced the reproducibility of the measurement of gastric UI using a Bland-Altman plot, resulting in a reduced deviation of each UI value. In addition, it was confirmed that errors in gastric UI decisions can be reduced by adjusting RGB values in diagnostic clinical data (i.e., adjusting to 100 is relatively better than adjusting to 50 or 200). Together, these results suggest that the new enhanced IA could be compatible with novel applications for measuring and evaluating gastric ulcers in clinical settings, meaning that the developed method could be used not only as an auxiliary tool for CCO, but also as a pipeline for ulcer diagnosis.

Gastrointestinal bleeding risk of non-vitamin K antagonist oral anticoagulants versus warfarin in general and after polypectomy: a population-based study with propensity score matching analysis.

BACKGROUND/AIMS: Gastrointestinal bleeding (GIB) risk for non-vitamin K antagonist oral anticoagulants (NOACs) compared with warfarin is largely unknown. We aimed to determine the risk of overall and post-polypectomy GIB for NOACs and warfarin. METHODS: Using the Korean National Health Insurance database, we created a cohort of patients who were newly prescribed NOACs or warfarin between July 2015 and December 2017 using propensity score matching (PSM). Kaplan-Meier analysis with log-rank test was performed to compare the risk of overall and post-polypectomy GIB between NOACs (apixaban, dabigatran, and rivaroxaban) and warfarin. Post-polypectomy GIB was defined as bleeding within 1 month after gastrointestinal endoscopic polypectomy. RESULTS: Out of 234,206 patients taking anticoagulants (187,687 NOACs and 46,519 warfarin), we selected 39,764 pairs of NOACs and warfarin users after PSM. NOACs patients showed significantly lower risk of overall GIB than warfarin patients (log-rank P<0.001, hazard ratio, 0.86; 95% confidence interval, 0.78-0.94; P=0.001). Among NOACs, apixaban showed the lowest risk of GIB. In the subgroup of 7,525 patients who underwent gastrointestinal polypectomy (lower gastrointestinal polypectomy 93.1%), 1,546 pairs were chosen for each group after PSM. The NOACs group showed a high risk of post-polypectomy GIB compared with the warfarin group (log-rank P=0.001, hazard ratio, 1.97; 95% confidence interval, 1.16-3.33; P=0.012). CONCLUSIONS: This nationwide, population-based study demonstrates that risk of overall GIB is lower for NOACs than for warfarin, while risk of post-polypectomy GIB is higher for NOACs than for warfarin.

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.

Low Bone Mineral Density in Young Patients Newly Diagnosed with Inflammatory Bowel Disease.

BACKGROUND: The prevalence and risk factors of low bone mineral density (BMD) in Asian patients newly diagnosed with inflammatory bowel disease (IBD) have not been fully suggested. AIMS: We aimed to examine the prevalence and risk factors of low BMD in young Korean patients newly diagnosed with IBD. METHODS: We prospectively enrolled 132 patients aged less than 50 years and newly diagnosed with IBD from six tertiary referral centers in Korea between November 2014 and April 2017. BMD was measured by dual-energy X-ray absorptiometry, and then the Z-score was determined. We defined low BMD as a Z-score ≤ - 1.0. RESULTS: Of 68 patients with ulcerative colitis (UC), 22 (32.4%) had low BMD. Also, of 64 patients with Crohn's disease (CD), 24 (37.5%) showed low BMD. Results from multivariate regression analysis identified the risk factors for low BMD as a high level of alkaline phosphatase (ALP) (≥ 140 U/L) (P = 0.010) in UC patients, and being underweight (body mass index ≤ 18.5 kg/m2) (P = 0.017) in CD patients. CONCLUSIONS: Our study showed that about one-third of newly diagnosed IBD Asian patients had low BMD. The clinical factors associated with low BMD were a high level of ALP in UC patients, and being underweight, in CD patients. Therefore, measurements of BMD in young patients should be considered at the diagnosis of IBD.

Antioxidant Analogue 6-Amino-2,4,5-Trimethylpyridin-3-ol Ameliorates Experimental Colitis in Mice.

BACKGROUND: Oxidative stress has been suggested to be a factor contributing to the disease severity of inflammatory bowel disease (IBD). BJ-1108, a derivative of 6-amino-2,4,5-trimethylpyridin-3-ol, is reported to significantly inhibit the generation of reactive oxygen species (ROS) in vitro. However, whether this molecule affects intestinal inflammation is largely unknown. We aimed to investigate the effect of BJ-1108 on dextran sulfate sodium (DSS)-induced experimental colitis in mice. METHODS: Colitis was induced in mice with DSS, and disease severity was estimated by evaluating body weight, colon length, histology, immune cell infiltration, and intestinal permeability. We examined the protective effects of BJ-1108 on barrier function using Caco-2 cells. Last, we estimated the impact of BJ-1108 on the phosphorylation of NF-kB, PI3K/AKT, and mitogen-activated protein kinases. RESULTS: Mice treated with BJ-1108 exhibited improved disease severity, as indicated by evaluations of body weight, histological scores, spleen weight, and infiltrates of T cells and macrophages. The administration of BJ-1108 inhibited the colonic mRNA expression of IL-6 and IL-1ß in vivo. Additionally, BJ-1108 limited intestinal permeability and enhanced the expression of tight junction (TJ) proteins such as claudin-1 and claudin-3 in the DSS-induced colitis model. In an in vitro model using Caco-2 cells, BJ-1108 ameliorated cytokine-induced ROS generation in a dose-dependent manner and remarkably recovered barrier dysfunction as estimated by evaluating transepithelial electrical resistance and TJ protein expression. BJ-1108 suppressed the NF-kB/ERK/PI3K pathway. CONCLUSIONS: This study demonstrated that BJ-1108 ameliorated intestinal inflammation in an experimental colitis mouse model, suggesting possible therapeutic implications for IBD.

Clinical Factors to Predict the Response to Concurrent Chemoradiotherapy and Survival in Esophageal Cancer Patients.

Background/Aims: Several clinical factors have been used to predict the response for concurrent chemoradiotherapy (CCRT); however, these factors are insufficient for prognostic predictions. We investigated clinical factors to assess whether they could be used to predict the response to CCRT and the survival of patients with esophageal cancer. Methods: Patients with esophageal cancer underwent CCRT from January 2005 to December 2015. Response to CCRT was classified as progressive disease (PD), stationary disease (SD), partial remission (PR), or complete remission (CR). Factors to predict the response to CCRT and patient survival were subsequently investigated. Results: A total of 535 esophageal cancer patients underwent CCRT. Four hundred ninety-three patients were followed up, and patient outcomes were investigated. In the adjusted analysis, patients with advanced stage disease (relative risk [RR], 0.28 in stage III and 0.12 in stage IV compared to stage I), poor performance status, circumferential involvement (RR, 0.61), and male sex (RR, 0.31) were less likely to achieve CR. Advanced stage disease (hazard ratio [HR], 1.71 in stage III/IV), poor CCRT response (HR, 2.82 in PR, 4.47 in SD, 4.77 in PD compared to CR), and poor performance status (HR, 1.38 in ECOG 2-4) were found to increase mortality. Conclusions: Advanced stage disease, poor performance status, male sex, and circumferential involvement were independent predictive factors for a poor response to CCRT. Advanced stage, poor performance status, and poor CCRT response were independent factors for decreased survival.

Fecal calprotectin is more accurate than fecal immunochemical test for predicting mucosal healing in quiescent ulcerative colitis: a prospective multicenter study.

Objective: Non-invasive stool tests, including the fecal immunochemical test (FIT) and fecal calprotectin (FC), are reliable biomarkers for mucosal healing (MH) in ulcerative colitis (UC). However, which fecal test is superior for predicting MH in inactive UC patients requires evaluation. We aimed to compare the accuracy of FIT and FC results for predicting MH in quiescent UC patients.Methods: This prospective, multicenter study was conducted at three tertiary hospitals. UC patients in clinical remission for at least three months underwent colonoscopy and MH was evaluated using the Mayo endoscopic sub-score (MES). The receiver operating characteristic (ROC) curve and cutoff value with the best accuracy for predicting MH were assessed.Results: Among 127 patients, 65 (51.2%) showed MH (MES = 0). The area under the curve (AUC) for predicting MH (MES = 0) was significantly higher for FC than for FIT (AUC 0.858 (95% confidence interval (CI) 0.784-0.913) vs. 0.707 (95% CI 0.620-0.784), p < .001); there was no difference when MH included MES = 1 (MES ≤ 1) (AUC 0.820 (95% CI 0.742-0.883) vs. 0.813 (95% CI 0.734-0.877), p = .891). When the cutoff value was 70 µg/g for FC and 10 ng/mL for FIT, the sensitivity, specificity, positive predictive value and negative predictive value were 89.2, 71, 76.3, and 86.3, respectively, for FC and 92.3, 50, 65.9, and 86.1, respectively, for FIT.Conclusion: FC is more accurate than FIT for predicting MH in quiescent UC patients. The superiority of FC might be related to the distinctive performance of FC in differentiating inflammatory levels, particularly in low-grade mucosal activity.

Randomised phase 3 trial: tegoprazan, a novel potassium-competitive acid blocker, vs. esomeprazole in patients with erosive oesophagitis.

BACKGROUND: Tegoprazan is a novel potassium-competitive acid blocker that has a fast onset of action and can control gastric pH for a prolonged period, which could offer clinical benefit in acid-related disorders. AIM: To confirm the non-inferiority of tegoprazan to esomeprazole in patients with erosive oesophagitis (EE). METHODS: In this multicentre, randomised, double-blind, parallel-group comparison study, 302 Korean patients with endoscopically confirmed EE (Los Angeles Classification Grades A-D) were randomly allocated to either tegoprazan (50 or 100 mg) or esomeprazole (40 mg) treatment groups for 4 or 8 weeks. The primary endpoint was the cumulative proportion of patients with healed EE confirmed by endoscopy up to 8 weeks from treatment initiation. Symptoms, safety and tolerability were also assessed. RESULTS: The cumulative healing rates at week 8 were 98.9% (91/92), 98.9% (90/91) and 98.9% (87/88) for tegoprazan 50 mg, tegoprazan 100 mg and esomeprazole 40 mg, respectively. Both doses of tegoprazan were non-inferior to esomeprazole 40 mg. The incidence of adverse events was comparable among the groups, and tegoprazan was well-tolerated. CONCLUSION: Once daily administration of tegoprazan 50 or 100 mg showed non-inferior efficacy in healing EE and tolerability to that of esomeprazole 40 mg.