Background/Aims: Fexuprazan, a novel potassium-competitive acid blocker, was developed for treating acid-related disorders. Pharmacokinetic and pharmacodynamic properties of fexuprazan, unlike those of proton pump inhibitors, are independent of food effect. This study aims to evaluate differences in efficacy and safety of fexuprazan in patients with erosive esophagitis (EE) according to the timing of dosing. Methods: In this multicenter, open-label noninferiority study, patients who had typical reflux symptoms with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg daily 30 minutes before or after meal. Treatment was completed after 2 weeks or 4 weeks when healing was endoscopically confirmed. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 4. Safety endpoints included treatment-emergent adverse events (TEAEs). Results: In the prior-to-meal group (n = 89) and after-meal group (n = 86), 4-week EE healing rates were 98.77% and 100.00% (difference, 0.01%; 95% CI, –0.01% to 0.04%) and 2-week EE healing rates were 95.77% and 97.14% (difference, 0.01%; 95% CI, –0.05% to 0.07%), respectively. TEAEs were 9.78% and 8.70% in the prior-to-meal group and the after-meal group, respectively. Conclusions Non-inferiority analysis revealed that taking fexuprazan after meal was non-inferior to taking fexuprazan before meals in patients with EE. The frequency of adverse events was similar between the 2 study groups. The drug is safe and effective for healing EE regardless of the timing of dosing.

Background/Aims: Fexuprazan, a novel potassium-competitive acid blocker, was developed for treating acid-related disorders. Pharmacokinetic and pharmacodynamic properties of fexuprazan, unlike those of proton pump inhibitors, are independent of food effect. This study aims to evaluate differences in efficacy and safety of fexuprazan in patients with erosive esophagitis (EE) according to the timing of dosing. Methods: In this multicenter, open-label noninferiority study, patients who had typical reflux symptoms with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg daily 30 minutes before or after meal. Treatment was completed after 2 weeks or 4 weeks when healing was endoscopically confirmed. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 4. Safety endpoints included treatment-emergent adverse events (TEAEs). Results: In the prior-to-meal group (n = 89) and after-meal group (n = 86), 4-week EE healing rates were 98.77% and 100.00% (difference, 0.01%; 95% CI, –0.01% to 0.04%) and 2-week EE healing rates were 95.77% and 97.14% (difference, 0.01%; 95% CI, –0.05% to 0.07%), respectively. TEAEs were 9.78% and 8.70% in the prior-to-meal group and the after-meal group, respectively. Conclusions Non-inferiority analysis revealed that taking fexuprazan after meal was non-inferior to taking fexuprazan before meals in patients with EE. The frequency of adverse events was similar between the 2 study groups. The drug is safe and effective for healing EE regardless of the timing of dosing.

Background/Aims: Fexuprazan, a novel potassium-competitive acid blocker, was developed for treating acid-related disorders. Pharmacokinetic and pharmacodynamic properties of fexuprazan, unlike those of proton pump inhibitors, are independent of food effect. This study aims to evaluate differences in efficacy and safety of fexuprazan in patients with erosive esophagitis (EE) according to the timing of dosing. Methods: In this multicenter, open-label noninferiority study, patients who had typical reflux symptoms with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg daily 30 minutes before or after meal. Treatment was completed after 2 weeks or 4 weeks when healing was endoscopically confirmed. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 4. Safety endpoints included treatment-emergent adverse events (TEAEs). Results: In the prior-to-meal group (n = 89) and after-meal group (n = 86), 4-week EE healing rates were 98.77% and 100.00% (difference, 0.01%; 95% CI, –0.01% to 0.04%) and 2-week EE healing rates were 95.77% and 97.14% (difference, 0.01%; 95% CI, –0.05% to 0.07%), respectively. TEAEs were 9.78% and 8.70% in the prior-to-meal group and the after-meal group, respectively. Conclusions Non-inferiority analysis revealed that taking fexuprazan after meal was non-inferior to taking fexuprazan before meals in patients with EE. The frequency of adverse events was similar between the 2 study groups. The drug is safe and effective for healing EE regardless of the timing of dosing.

This study investigated the molecular mechanism of phenotypic switching of vascular smooth muscle cells (VSMCs), which play a crucial role in vascular remodeling using 9H-Carbazol-3-yl 4-aminobenzoate (CAB). CAB significantly attenuated platelet-derived growth factor (PDGF)-induced VSMC proliferation and migration. CAB suppressed PDGF-induced STAT3 activation by directly binding to the SH2 domain of STAT3. Downregulation of STAT3 phosphorylation by CAB attenuated CIAPIN1/JAK2/STAT3 axis through a decrease in CIAPIN1 transcription. Furthermore, abrogated CIAPIN1 decreased KLF4-mediated VSMC dedifferentiation and increased CDKN1B-induced cell cycle arrest and MMP9 suppression. CAB inhibited intimal hyperplasia in injury-induced neointima animal models by inhibition of the CIAPIN1/JAK2/STAT3 axis. However, CIAPIN1 overexpression attenuated CAB-mediated suppression of VSMC proliferation, migration, phenotypic switching, and intimal hyperplasia. Our study clarified the molecular mechanism underlying STAT3 inhibition of VSMC phenotypic switching and vascular remodeling and identified novel active CAB. These findings demonstrated that STAT3 can be a major regulator to control CIAPIN1/JAK2/STAT3 axis that may be a therapeutic target for treating vascular proliferative diseases.

Background/Aims: Risk scoring systems for upper gastrointestinal (UGI) bleeding have not been well validated for tumor bleeding. This study aimed to identify risk factors for mortality in patients with UGI cancer bleeding and to develop a predictive model. Methods: Consecutive patients with UGI cancers who underwent esophagogastroduodenoscopy for suspected bleeding were retrospectively included. Patient characteristics, endoscopic findings and 30-day mortality were assessed. A predictive model was made based on risk factors for mortality using logistic regression, and the area under the curve (AUC) of this model was calculated. It was then compared with other risk scoring systems. Results: In a total of 264 patients, 193 had tumor bleeding. Among them, 108 (56.0%), 76 (39.4%), and nine (4.7%) patients received conservative treatment, endoscopic therapy, and non-endoscopic hemostasis, respectively. Rebleeding occurred in 23 (21.3%), 26 (34.2%), and one (11.1%) patient(s), respectively. Our new model is composed of altered mental status, renal failure, rebleeding, age older than 65 years, and low serum albumin (all p<0.05). This model predicted 30-day mortality with an AUC of 0.79 (95% confidence interval, 0.72 to 0.86), which was significantly higher than AUCs of the Glasgow-Blatchford score, Rockall, and AIMS65 score (AUC=0.61, 0.64, and 0.69, respectively, all p<0.05). Conclusions Our new scoring system provides a better prediction of 30-day mortality than existing scoring systems in patients with UGI cancer bleeding. This new scoring system can be used to predict and prepare these patients who are known to have high mortality.

Background/Aims: This study investigated whether the personality traits of endoscopists are associated with the effect of interventions for the improvement of colonoscopy quality. Methods: This prospective, multicenter, single-blind study was performed with 13 endoscopists in three health screening centers over a 12-month period. Quality indicators (QIs), including adenoma detection rate (ADR), polyp detection rate (PDR), and withdrawal time, were measured every 3 months. Consecutive interventions for the improvement of colonoscopy quality were conducted every 3 months, which included the personal notification of QIs, the in-group notification of QIs, and finally a targeted “quality education” session. The personality traits of each endoscopist were evaluated for perfectionism, fear of negative evaluation, and cognitive flexibility after the last QI assessment. Results: A total of 4,095 colonoscopies were evaluated to measure the QIs of the individual endoscopists for 12 months. The mean ADR, PDR, and withdrawal time of the 13 endoscopists were 32.3%, 47.7%, and 394 seconds at baseline and increased to 39.0%, 55.1%, and 430 seconds by the end of the study (p=0.003, p=0.006, and p=0.004, respectively). Among the three interventions, only quality education significantly improved QIs: ADR, 36.0% to 39.0% (odds ratio, 1.28; 95% confidence interval, 1.01 to 1.63). The improvement of ADR and PDR by education was significantly associated with perfectionism (r=0.617, p=0.033 and r=0.635, p=0.027, respectively) and fear of negative evaluation (r=0.704, p=0.011 and r=0.761, p=0.004, respectively). Conclusions Education can improve colonoscopy quality, and its effect size is associated with an endoscopist’s personal traits such as perfectionism and fear of negative evaluation (ClinicalTrials.gov Registry NCT03796169).

Background and Objectives: Heart failure (HF) is a leading cause of hospitalization and death worldwide. The Steady Movement with Innovating Leadership for Heart Failure (SMILE HF) aims to evaluate the clinical characteristics, management, hospital course, and long-term outcomes of patients hospitalized for acute HF in South Korea. Methods: This prospective, observational multicenter cohort study was conducted on consecutive patients hospitalized for acute HF in nine university hospitals since September 2019. Enrolment of 2000 patients should be completed in 2024, and follow-up is planned through 2025. Results: Interim analysis of 1,052 consecutive patients was performed to understand the baseline characteristics. The mean age was 69±15 years; 57.6% were male. The mean left ventricular ejection fraction was 39±15%. The prevalences of HF with reduced ejection fraction, HF with mildly reduced ejection fraction, and HF with preserved ejection fraction were 50.9%, 15.3%, and 29.2%. Ischemic cardiomyopathy (CMP) was the most common etiology (32%), followed by tachycardia-induced CMP (12.8%) and idiopathic dilated CMP (9.5%). The prescription rate of angiotensin-converting enzyme inhibitor/angiotensin receptor blockers/angiotensin receptor/ neprilysin inhibitor, beta-blockers, spironolactone, and sodium-glucose cotransporter-2 inhibitors at discharge were 76.8%, 66.5%, 50.0%, and 17.5%, respectively. The post-discharge 90-day mortality and readmission rates due to HF aggravation were 2.0% and 6.4%, respectively. Our analysis reveals the current state of acute HF in South Korea. Conclusions Our interim analysis provides valuable insights into the clinical characteristics, management, and early outcomes of acute HF patients in South Korea, highlighting the current state and treatment patterns in this population.

Background: s/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.

Background/Aims: Efficacy of proton pump inhibitors is limited in patients with nonerosive reflux disease (NERD). The aim of this study was to comparatively evaluate the efficacy and safety of esomeprazole with sodium bicarbonate and esomeprazole alone. Methods: This was a multicenter, randomized, double-blind, active-controlled, noninferiority comparative study. A total of 379 patients with NERD were randomly allocated to receive either EsoduoⓇ/sup> (esomeprazole 20 mg with sodium bicarbonate 800 mg) or NexiumⓇ/sup> (esomeprazole 20 mg) once daily for 4 weeks from January 2019 to December 2019. The patients had a history of heartburn for at least 2 days in the week before randomization as well as in the last 3 months and no esophageal mucosal breaks on endoscopy. The primary endpoint was a complete cure of heartburn at week 4. The secondary and exploratory endpoints as well as the safety profiles were compared in the groups at weeks 2 and 4. Results: A total of 355 patients completed the study (180 in the EsoduoⓇ/sup> group and 175 in the NexiumⓇ/sup> group). The proportions of patients without heartburn in the entire 4th week of treatment were not different between the two groups (33.33% in the EsoduoⓇ/sup> group and 35% in the NexiumⓇ/sup> group, p=0.737). There were no significant differences in most of the secondary and exploratory endpoints as well as the safety profiles. Conclusions EsoduoⓇ/sup> is as effective and safe as NexiumⓇ/sup> for managing typical symptoms in patients with NERD (ClinicalTrial.gov identifier: NCT03928470).

Benign mediastinal cysts are challenging to diagnose. Although Endoscopic Ultrasound (EUS) and EUS-guided fine needle aspiration (FNA) can accurately diagnose mediastinal foregut cysts, little is known about their complications. This paper reports a rare case in which EUS-FNA performed on mediastinal hemangioma resulted in an aortic hematoma. A 29-year-old female patient was commissioned for EUS of an asymptomatic accidental mediastinal lesion. Chest CT revealed a 4.9×2.9×10.1 cm thin-walled cystic mass in the posterior mediastinum. EUS revealed a large, anechoic cystic lesion with a regular thin wall with negative Doppler. EUS-guided FNA was performed using a single-use 19-gauge aspiration needle (EZ Shot 3; Olympus, Tokyo, Japan), and approximately 70 cc of serous pinkish fluid was aspirated. The patient was in a stable condition with no signs of acute complication. One day after EUS-FNA, thoracoscopic resection for mediastinal mass was conducted. The purple and multi-loculated large cyst was removed. Upon removal, however, an aortic hematoma caused by a focal descending aortic wall injury was observed. After a few days of close observation, the patient was discharged upon stable 3D aorta angio CT findings. This paper reports a rare and severe complication of EUS-FNA, in which an aspiration needle caused a direct injury to the aorta. The injection must be performed carefully to avoid damaging the adjacent organs or digestive tract walls.