Reliable preclinical models for assessing drug-induced cardiotoxicity are essential to reduce the high rate of drug withdrawals during development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising platform for such assessments due to their expression of cardiacspecific ion channels and electrophysiological properties. In this study, we investigated the effects of eight arrhythmogenic drugs—E4031, nifedipine, mexiletine, JNJ303, flecainide, moxifloxacin, quinidine, and ranolazine—on hiPSC-CMs derived from both healthy individuals and a long QT syndrome (LQTS) patient using multielectrode array systems. The results demonstrated dose-dependent changes in field potential duration and arrhythmogenic risk, with LQTS-derived hiPSC-CMs showing increased sensitivity to hERG channel blockers such as E4031. Furthermore, the study highlights the potential of hiPSC-CMs to model disease-specific cardiac responses, providing insights into genetic predispositions and personalized drug responses.Despite challenges related to the immaturity of hiPSC-CMs, their ability to recapitulate human cardiac electrophysiology makes them a valuable tool for preclinical cardiotoxicity assessments. This study underscores the utility of integrating patientderived hiPSC-CMs with advanced analytical platforms, such as multi-electrode array systems, to evaluate drug-induced electrophysiological changes. These findings reinforce the role of hiPSC-CMs in drug development, facilitating safer and more efficient screening methods while supporting precision medicine applications.

Reliable preclinical models for assessing drug-induced cardiotoxicity are essential to reduce the high rate of drug withdrawals during development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising platform for such assessments due to their expression of cardiacspecific ion channels and electrophysiological properties. In this study, we investigated the effects of eight arrhythmogenic drugs—E4031, nifedipine, mexiletine, JNJ303, flecainide, moxifloxacin, quinidine, and ranolazine—on hiPSC-CMs derived from both healthy individuals and a long QT syndrome (LQTS) patient using multielectrode array systems. The results demonstrated dose-dependent changes in field potential duration and arrhythmogenic risk, with LQTS-derived hiPSC-CMs showing increased sensitivity to hERG channel blockers such as E4031. Furthermore, the study highlights the potential of hiPSC-CMs to model disease-specific cardiac responses, providing insights into genetic predispositions and personalized drug responses.Despite challenges related to the immaturity of hiPSC-CMs, their ability to recapitulate human cardiac electrophysiology makes them a valuable tool for preclinical cardiotoxicity assessments. This study underscores the utility of integrating patientderived hiPSC-CMs with advanced analytical platforms, such as multi-electrode array systems, to evaluate drug-induced electrophysiological changes. These findings reinforce the role of hiPSC-CMs in drug development, facilitating safer and more efficient screening methods while supporting precision medicine applications.

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: Complete revascularization has demonstrated better outcomes in patients with acute myocardial infarction (AMI) and multivessel disease. However, in the case of left main (LM) culprit lesion AMI with multivessel disease, there is limited evidence to suggest that complete revascularization is better. Methods: We reviewed 16,831 patients in the Korea Acute Myocardial Infarction Registry who were treated from July 2016 to June 2020, and 399 patients were enrolled with LM culprit lesion AMI treated with percutaneous coronary intervention. We categorized the patients as those treated with complete revascularization (n=295) or incomplete revascularization (n=104). The study endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, myocardial infarction, ischemia-driven revascularization, stent thrombosis, and stroke. We performed propensity score matching (PSM) and analyzed the incidence of MACCE at 1 year. Results: After PSM, the two groups were well balanced. There was no significant difference between the two groups in MACCE at 1 year (12.1% vs. 15.2%; hazard ratio, 1.28; 95% confidence interval, 0.60–2.74; p=0.524) after PSM. The components of MACCE and major bleeding were also not significantly different. Conclusion There was no significant difference in clinical outcomes between the groups treated with complete or incomplete revascularization for LM culprit lesion AMI with multivessel disease.

Background and Objectives: Outcomes of deferring percutaneous coronary intervention (PCI) without invasive physiologic assessment for intermediate coronary lesions is uncertain.We sought to compare long-term outcomes between medical treatment and PCI of intermediate lesions without invasive physiologic assessment. Methods: A total of 899 patients with intermediate coronary lesions between 50% and 70% diameter-stenosis were randomized to the conservative group (n=449) or the aggressive group (n=450). For intermediate lesions, PCI was performed in the aggressive group, but was deferred in the conservative group. The primary endpoint was major adverse cardiac events (MACE, a composite of all-cause death, myocardial infarction [MI], or ischemia-driven any revascularization) at 3 years. Results: The number of treated lesions per patient was 0.8±0.9 in the conservative group and 1.7±0.9 in the aggressive group (p=0.001). At 3 years, the conservative group had a significantly higher incidence of MACE than the aggressive group (13.8% vs. 9.3%; hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.00–2.21; p=0.049), mainly driven by revascularization of target intermediate lesion (6.5% vs. 1.1%; HR, 5.69; 95% CI, 2.20–14.73;p<0.001). Between 1 and 3 years after the index procedure, compared to the aggressive group, the conservative group had significantly higher incidence of cardiac death or MI (3.2% vs.0.7%; HR, 4.34; 95% CI, 1.24–15.22; p=0.022) and ischemia-driven any revascularization. Conclusions For intermediate lesions, medical therapy alone, guided only by angiography, was associated with a higher risk of MACE at 3 years compared with performing PCI, mainly due to increased revascularization.

Background: A nationwide Rehabilitation at Home Care Pilot Program for patients undergoing lower extremity orthopedic surgeries has been ongoing since 2020. The program was designed to improve clinical outcomes through early mobilization and rehabilitation after discharge. This study aimed to analyze the interim data to assess its effectiveness and suggest improvements, particularly for older patients who are more vulnerable compared to younger patients. Methods: We analyzed the data of 872 patients from seven hospitals. Patients were divided into an older-age group (OG; ≥60 years) and younger-age group (YG; <60 years). The Berg Balance Scale (BBS) and Numeric Rating Scale (NRS) scores for pain were the main outcomes. Results: Participants were categorized into OG (n=801) and YG (n=71). The most common surgeries were knee joint replacement (63.7%) in OG and hip joint replacement in YG (77.5%). It took more days to enroll in the pilot program in OG (4.4 days) than YG (3.2 days). OG showed less improvement in BBS than YG for all surgeries (23.3 vs. 31.9) and hip joint surgery (19.8 vs. 33.5). In patients with hip joint replacement in OG, those with a higher number of comorbidities (≥3) showed less BBS improvement than those with fewer comorbidities (<3). In the pain domain, NRS scores decreased in both groups. Conclusion The postoperative rehabilitation education program appeared to be effective in improving physical function and reducing pain severity, though the improvement was less obvious in older patients who may require a more comprehensive approach compared to younger patients.

Purpose: Common bile duct (CBD) stone recurrence after laparoscopic CBD exploration (LCBDE) is relatively common. No studies have been conducted evaluating the safety and feasibility of re-do LCBDE in the treatment of recurrent CBD stones. Methods: This single-center retrospective study reviewed 340 consecutive patients who underwent LCBDE for CBD stones between January 2004 and December 2020. Patients with pancreatobiliary malignancies and those who underwent other surgical procedures were excluded. Results: Of the 340 included patients, 45 experienced a recurrence after a mean follow-up period of 24.2 months. Of them, 18 underwent re-do LCBDE, 20 underwent endoscopic intervention, 2 underwent radiologic intervention, and 5 underwent observation. Re-do LCBDE and initial LCBDE showed similar surgical outcomes in terms of operative time (113.1 minutes vs. 107.5 minutes, P = 0.515), estimated blood loss (42.5 mL vs. 49.1 mL, P = 0.661), open conversion rate (2.9% vs. 0%, P = 0.461), postoperative complication (15.3% vs. 22.2%, P = 0.430), and postoperative hospital stay (6.5 days vs. 6.4 days, P = 0.921). Comparing re-do LCBDE and nonsurgical treatment (endoscopic or radiologic), no statistically significant differences were noted in posttreatment complication (22.2% vs. 13.6%, P = 0.477), hospital stay (6.4 days vs.7.3 days, P = 0.607), and recurrence (50.0% vs. 36.4%, P = 0.385). The clearance rate was higher in the re-do LCBDE group than in the nonsurgical group (100% vs. 81.8%, P = 0.057). Conclusion Compared to initial LCBDE and endoscopic or radiological treatments, re-do LCBDE for recurrent CBD stones is a treatment option worth considering in selected patients.

Reliable preclinical models for assessing drug-induced cardiotoxicity are essential to reduce the high rate of drug withdrawals during development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising platform for such assessments due to their expression of cardiacspecific ion channels and electrophysiological properties. In this study, we investigated the effects of eight arrhythmogenic drugs—E4031, nifedipine, mexiletine, JNJ303, flecainide, moxifloxacin, quinidine, and ranolazine—on hiPSC-CMs derived from both healthy individuals and a long QT syndrome (LQTS) patient using multielectrode array systems. The results demonstrated dose-dependent changes in field potential duration and arrhythmogenic risk, with LQTS-derived hiPSC-CMs showing increased sensitivity to hERG channel blockers such as E4031. Furthermore, the study highlights the potential of hiPSC-CMs to model disease-specific cardiac responses, providing insights into genetic predispositions and personalized drug responses.Despite challenges related to the immaturity of hiPSC-CMs, their ability to recapitulate human cardiac electrophysiology makes them a valuable tool for preclinical cardiotoxicity assessments. This study underscores the utility of integrating patientderived hiPSC-CMs with advanced analytical platforms, such as multi-electrode array systems, to evaluate drug-induced electrophysiological changes. These findings reinforce the role of hiPSC-CMs in drug development, facilitating safer and more efficient screening methods while supporting precision medicine applications.

Reliable preclinical models for assessing drug-induced cardiotoxicity are essential to reduce the high rate of drug withdrawals during development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising platform for such assessments due to their expression of cardiacspecific ion channels and electrophysiological properties. In this study, we investigated the effects of eight arrhythmogenic drugs—E4031, nifedipine, mexiletine, JNJ303, flecainide, moxifloxacin, quinidine, and ranolazine—on hiPSC-CMs derived from both healthy individuals and a long QT syndrome (LQTS) patient using multielectrode array systems. The results demonstrated dose-dependent changes in field potential duration and arrhythmogenic risk, with LQTS-derived hiPSC-CMs showing increased sensitivity to hERG channel blockers such as E4031. Furthermore, the study highlights the potential of hiPSC-CMs to model disease-specific cardiac responses, providing insights into genetic predispositions and personalized drug responses.Despite challenges related to the immaturity of hiPSC-CMs, their ability to recapitulate human cardiac electrophysiology makes them a valuable tool for preclinical cardiotoxicity assessments. This study underscores the utility of integrating patientderived hiPSC-CMs with advanced analytical platforms, such as multi-electrode array systems, to evaluate drug-induced electrophysiological changes. These findings reinforce the role of hiPSC-CMs in drug development, facilitating safer and more efficient screening methods while supporting precision medicine applications.