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.

Atherosclerosis is a major contributor to cardiovascular disease, characterized by inflammation and lipid accumulation in arterial walls, leading to plaque formation. Elevated low-density lipoprotein cholesterol is a primary risk factor for atherosclerosis. All-trans retinoic acid (ATRA), a metabolite of vitamin A, has demonstrated anti-inflammatory effects and potential in regulating vascular injury. 9-cisretinoic acid (9cRA) is an active metabolite of vitamin A and activates the retinoid X receptor. This study investigates whether potassium retinoate (PA9RA), a synthetic combination of ATRA and 9cRA, offers superior efficacy in treating atherosclerosis compared to established treatments such as clopidogrel and atorvastatin. Male ApoE -/- mice were fed a Western-type diet and treated with PA9RA, clopidogrel, or atorvastatin for 10 weeks. The body weight, organ weight, serum biochemistry, and histopathology, including atherosclerotic lesion area and liver steatosis were assessed. PA9RA treatment led to a significant reduction in body weight and inguinal fat, with the 45 mg/kg/day dose showing marked efficacy in decreasing atherosclerotic lesion size and ameliorating liver steatosis. Histopathological evaluation revealed decreased foam cell formation and improved liver histology in PA9RA-treated groups compared to controls. Notable side effects included epidermal hyperplasia and gastric hyperplasia at high doses of PA9RA. PA9RA exhibits superior efficacy over clopidogrel and atorvastatin in ameliorating atherosclerosis and fatty liver in ApoE –/–mice. This study highlights PA9RA's potential as a promising therapeutic agent for atherosclerosis. Further research is needed to elucidate its mechanisms of action and assess long-term safety and efficacy.

Purpose: Finasteride and dutasteride are used to treat benign prostatic hyperplasia (BPH) and reduce the risk of developing prostate cancer. Finasteride blocks only the type 2 form of 5-alpha-reductase, whereas dutasteride blocks both type 1 and 2 forms of the enzyme. Previous studies suggest the possibility that dutasteride may be superior to finasteride in preventing prostate cancer. We directly compared the effects of finasteride and dutasteride on the risk of prostate cancer in patients with BPH using a pooled analysis of 15 real-world databases. Materials and Methods: We conducted a multicenter, cohort study of new-users of finasteride and dutasteride. We include patients who were prescribed 5 mg finasteride or dutasteride for the first time to treat BPH and had at least 180 days of prescription. We excluded patients with a history of prostate cancer or a prostate-specific antigen level ≥ 4 ng/mL before the study drug prescription. Cox regression analysis was performed to examine the hazard ratio (HR) for prostate cancer after propensity score (PS) matching. Results: A total of 8,284 patients of new-users of finasteride and 8,670 patients of new-users of dutasteride were included across the 15 databases. In the overall population, compared to dutasteride, finasteride was associated with a lower risk of prostate cancer in both on-treatment and intent-to-treat time-at-risk periods. After 1:1 PS matching, 4,897 patients using finasteride and 4,897 patients using dutasteride were enrolled in the present study. No significant differences were observed for risk of prostate cancer between finasteride and dutasteride both on-treatment (HR=0.66, 95% confidence interval [CI]: 0.44–1.00; p=0.051) and intent-to-treat time-at-risk periods (HR=0.87, 95% CI: 0.67–1.14; p=0.310). Conclusions Using real-world databases, the present study demonstrated that dutasteride was not associated with a lower risk of prostate cancer than finasteride in patients with BPH.

Background: Respiratory infections play a major role in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study assessed the prevalence of bacterial and viral pathogens and their clinical impact on patients with AECOPD. Methods: This retrospective study included 1,186 patients diagnosed with AECOPD at 28 hospitals in South Korea between 2015 and 2018. We evaluated the identification rates of pathogens, basic patient characteristics, clinical features, and the factors associated with infections by potentially drug-resistant (PDR) pathogens using various microbiological tests. Results: Bacteria, viruses, and both were detected in 262 (22.1%), 265 (22.5%), and 129 (10.9%) of patients, respectively. The most common pathogens included Pseudomonas aeruginosa (17.8%), Mycoplasma pneumoniae (11.2%), Streptococcus pneumoniae (9.0%), influenza A virus (19.0%), rhinovirus (15.8%), and respiratory syncytial virus (6.4%). Notably, a history of pulmonary tuberculosis (odds ratio [OR], 1.66; p=0.046), bronchiectasis (OR, 1.99; p=0.032), and the use of a triple inhaler regimen within the past 6 months (OR, 2.04; p=0.005) were identified as significant factors associated with infection by PDR pathogens. Moreover, patients infected with PDR pathogens exhibited extended hospital stays (15.9 days vs. 12.4 days, p=0.018) and higher intensive care unit admission rates (15.9% vs. 9.5%, p=0.030). Conclusion This study demonstrates that a variety of pathogens are involved in episodes of AECOPD. Nevertheless, additional research is required to confirm their role in the onset and progression of AECOPD.

Purpose: This study assessed the reproducibility and clinical value of the vascular index (VI), derived from superb microvascular imaging (SMI) using Doppler ultrasonography, for evaluating renal function in transplanted kidneys. Methods: This retrospective study included 63 renal transplant patients who underwent grayscale and Doppler ultrasonography with SMI from January 2022 to February 2023. The VI of the transplanted kidneys was measured using three methods (VI_box, VI_F1, VI_F2). The VI was compared across chronic kidney disease (CKD) groups categorized by estimated glomerular filtration rate (eGFR) and Kidney Disease: Improving Global Outcomes (KDIGO) CKD risk groups based on eGFR and albuminuria. The correlation between VI and renal function was evaluated. Univariate and multivariate linear regression analyses were used to identify predictors of eGFR. Results: Significant differences in VI were observed among CKD groups based on eGFR (VI_box, P=0.001; VI_F1, P<0.001; VI_F2, P<0.001) and KDIGO CKD groups based on eGFR and albuminuria (VI_box, P=0.039; VI_F1, P=0.001; VI_F2, P<0.001). VI_F1 and VI_F2 demonstrated moderate/high correlations with eGFR (r=0.627, P<0.001 and r=0.657, P<0.001, respectively) and serum creatinine (r=-0.626, P<0.001 and r=-0.649, P<0.001, respectively). VI_box moderately correlated with eGFR (r=0.445, P<0.001). Multivariate regression identified the urine albumincreatinine ratio (ACR) (adjusted odds ratio [aOR], 1.122; 95% confidence interval [CI], -0.007 to, 0.000; P=0.030) and VI_F2 (aOR, 1.114; 95% CI, 0.466 to 1.235; P<0.001) were independently associated with eGFR. Conclusion The VI measured by drawing a region of interest along the border of the transplanted kidney in SMI (VI_F2) is highly reproducible and correlates well with eGFR. Both VI_F2 and ACR independently predict eGFR.

Purpose: Cognitive behavioral therapy (CBT) has long been recognized as an effective treatment for depression and suicidality.Virtual reality (VR) technology is widely used for cognitive training for conditions such as anxiety disorder and post-traumatic stress disorder, but little research has considered VR-based CBT for depressive symptoms and suicidality. We tested the effectiveness and safety of a VR-based CBT program for depressive disorders. Materials and Methods: We recruited 57 participants from May 2022 through February 2023 using online advertisements. This multi-center, assessor-blinded, randomized, controlled exploratory trial used two groups: VR treatment group and treat as usual (TAU) group. VR treatment group received a VR mental health training/education program. TAU group received standard pharmacotherapy. Assessments were conducted at baseline, immediately after the 6-week treatment period, and 4 weeks after the end of the treatment period in each group. Results: Depression scores decreased significantly over time in both VR treatment and TAU groups, with no differences between the two groups. The suicidality score decreased significantly only in VR group. No group differences were found in the remission or response rate for depression, perceived stress, or clinical severity. No adverse events or motion sickness occurred during the VR treatment program. Conclusion VR CBT treatment for major depressive disorder has the potential to be equivalent to the gold-standard pharmacotherapy in reducing depressive symptoms, suicidality, and related clinical symptoms, with no difference in improvement found in this study. Thus, VR-based CBT might be an effective alternative to pharmacotherapy for depressive disorders.

Purpose: Improvement of left ventricular (LV) diastolic dysfunction (DD) is known to be a good prognostic factor in patients with heart failure with reduced ejection fraction (EF). In the present study, we investigated the predisposing risk factors affecting the reversibility of LV diastolic filling pattern (DFP) in patients with preserved EF. Materials and Methods: A total of 600 patients with pseudonormal LVDFP and preserved EF who underwent follow-up echocardiography were enrolled between 2011 and 2020. We compared their index and follow-up echocardiography findings and determined the predisposing risk factor affecting the reversibility of LVDFP. Results: Comparing the index and follow-up echocardiography findings showed that 379 (63%) patients had improved to normal or impaired relaxation LVDFP (improved group) and 221 (37%) patients had maintained or worsened LVDFP (unimproved group).The incidence of paroxysmal atrial fibrillation (PAF) was significantly higher in the unimproved group than in the improved group (4.7% vs. 9.5%, p=0.026). After adjustment for relevant clinical risk factors of diastolic dysfunction, PAF was determined to be an independent predisposing risk factor for the unimproved LVDFP (odds ratio: 2.10, 95% confidence interval: 1.06–4.15, p=0.033).Among the parameters of diastolic dysfunction in follow-up echocardiography, the left atrial volume index, mean E/A ratio, and E/e' were significantly improved in patients without PAF but remained in patients with PAF. Conclusion We identified that PAF was an independent predisposing risk factor of the unimproved LVDFP in patients with pseudonormal LVDFP and preserved EF. Therefore, early detection and management of PAF might be required in patients with LVDD and preserved EF to prevent adverse cardiovascular events.

Objectives: . Salivary gland tumors present a diagnostic challenge, with preoperative false-negative results frequently leading to an unexpected diagnosis of malignancy after parotidectomy. This study was conducted to explore the clinical utility of preoperative core needle biopsy (CNB) in diagnosing malignancies before primary parotidectomy and to assess the prognostic implications of CNB for parotid gland cancers. Methods: . This retrospective cohort study included 615 patients who underwent preoperative CNB and parotidectomy for primary parotid tumors from 2003 to 2023 at a tertiary referral hospital. Among these patients, 102 who were diagnosed with primary parotid malignancy following parotidectomy were examined regarding survival outcomes. Disease-free survival (DFS) and predictive factors were assessed through univariable and multivariable analyses. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of CNB were determined. These metrics were then compared to those of a separate cohort of 547 patients who underwent ultrasound-guided fine needle aspiration (FNA) and parotidectomy within the same timeframe. Results: . In the CNB group, the 5-year predicted DFS was 86.9% (95% CI, 79.2%–95.3%). Multivariable analysis identified male sex (hazard ratio [HR], 8.48; 95% CI, 1.05–68.76) and a CNB finding of malignancy (HR, 8.20; 95% CI, 1.01–66.15) as factors significantly associated with decreased DFS. CNB demonstrated significantly higher sensitivity (89.0%; 95% CI, 81.2%–94.4%) and NPV (97.6%; 95% CI, 95.7%–98.8%) compared to FNA, which had a sensitivity of 45.2% (95% CI, 33.5%–57.3%) and an NPV of 90.8% (95% CI, 87.7%–93.3%). Conclusion . Preoperative CNB may be predictive of parotid cancer prognosis. Patients receiving a diagnosis of malignancy on preoperative CNB demonstrated a worse prognosis compared to those with a “less-than-malignant” diagnosis. Additionally, CNB exhibited higher sensitivity than FNA in identifying malignancies of the parotid gland.

Background/Aims: Chronic gastroesophageal reflux disease (GERD) requires symptom relief and treatment of associated conditions. In this study, we aimed to compare anti-reflux mucosectomy (ARMS) and Stretta radiofrequency (SRF) for treating patients with chronic GERD who are unresponsive to proton pump inhibitors (PPIs) and to identify the indications for each procedure. Methods: Data of patients who underwent ARMS or SRF between March 2021 and April 2023 were analyzed. Changes in GERD questionnaire (GERDQ) scores, endoscopic Los Angeles (LA) grade, flap valve grade (FVG) based on Hill’s type, EndoFLIP distensibility index (DI), endoscopic Barrett’s epithelium (BE) resolution rate, and PPI withdrawal rate were compared between the two groups. Results: Improvements in the GERDQ scores and PPI withdrawal rates were similar between the groups. The ARMS group showed significantly better changes in endoscopic LA grade, FVG, and EndoFLIP DI than the SRF group. The complications were more prevalent in the ARMS group than in the SRF group. Conclusions The change in endoscopic LA grade before and after the procedure was significantly higher in the ARMS group than in the SRF group. Significant improvements in endoscopic FVG, BE resolution, and EndoFLIP DI were observed only with the ARMS group.