Purpose: Cannabidiol (CBD) is a promising treatment option for pediatric drug-resistant epilepsy (DRE). The aim of this study was to assess the tolerability and safety of CBD in a single-center retrospective cohort based on real-world clinical experience. Methods: This study included 71 pediatric patients (median age, 8.9 years; interquartile range [IQR], 6.2 to 14.0) with Lennox–Gastaut syndrome who received purified CBD (Epidiolex, GW Pharmaceuticals) between March 2019 and July 2024. All patients had previously failed treatment with more than five anti-seizure medications (ASMs). Responder rate (≥50% seizure frequency reduction), retention rate, adverse effects (AEs), and predictors of favorable treatment response were analyzed over a median follow-up of 21.3 months (IQR, 2.8 to 38.5). Results: The initial responder rate during the first 3 months was 45.1%, which increased to 70.8% at 18 months and 63.0% at 24 months. The retention rate at 24 months was 52.4% (33/71). Seven patients (9.9%) achieved seizure freedom beyond 24 months of CBD therapy, and five of these patients were able to reduce their concomitant ASM burden. AEs were observed in 39.4% (28/71) of patients, with the most frequent being somnolence (20 cases) and increased seizure frequency (six cases); 92.9% of AEs occurred within the first 3 months of treatment. No serious AEs requiring treatment discontinuation were identified. Conclusion In this real-world study, CBD demonstrated potential as an adjunctive therapy with manageable AEs. These findings highlight that CBD can reduce seizure frequency while maintaining tolerability in pediatric patients with DRE.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine that selectively targets cancer cells and induces apoptosis. However, many cancers, including bladder cancer, develop resistance to TRAIL, limiting the efficacy of TRAIL-based therapies. This study investigated whether betulinic acid (BA), a pentacyclic triterpenoid with anticancer and chemosensitizing properties, increases TRAIL-mediated apoptosis in TRAIL-resistant human bladder cancer cells. Combination treatment with BA and TRAIL significantly increased cytotoxicity and apoptosis compared to either treatment alone. This combination treatment also increased reactive oxygen species (ROS) production, increased Bax expression and Bid cleavage (tBid formation), and downregulated Bcl-2 levels. These effects were accompanied by caspase activation via extrinsic and intrinsic pathways, leading to cytochrome c release via mitochondrial membrane destabilization, thereby contributing to increased apoptosis. Furthermore, the combination treatment inhibited phosphoinositide 3-kinase (PI3K) and Akt phosphorylation; this effect was amplified by a PI3K inhibitor but abrogated by ROS inhibition. Collectively, our results suggest that BA sensitizes bladder cancer cells to TRAILinduced apoptosis via ROS-dependent activation of the apoptotic pathway and inhibition of PI3K/Akt signaling. Therefore, the BA and TRAIL combination exhibits potential to overcome TRAIL resistance in human bladder cancer.

Background: s/Aims: The patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M variant has been implicated in metabolic dysfunction-associated steatotic liver disease (MASLD), but its role in hepatocellular carcinoma (HCC) development is unclear. This study examines the association between the PNPLA3 I148M variant and HCC occurrence. Methods: A total of 562 MASLD patients, with and without HCC, were prospectively and consecutively enrolled at two universityaffiliated hospital between June 2024 and June 2025. Genomic DNA was extracted from buccal swabs or liver biopsy samples, and single nucleotide polymorphism genotyping was performed to determine the rs738409 genotype at codon 148 of PNPLA3. The histological grade of HCC was assessed using the Edmondson-Steiner (ES) grading system in patients who underwent core-needle liver biopsy. Results: Among 474 non-HCC patients, the GG genotype was found in 39.9%, GC in 37.1%, and CC in 23.0%. In 88 HCC patients, these frequencies were 45.5%, 36.4%, and 18.2%, respectively. No significant differences in GG genotype distribution were observed between HCC and non-HCC groups (P=0.509), nor in subgroups by sex, age, obesity status, cirrhosis status, fibrosis-4 index, or liver stiffness measurement. However, among HCC patients with histological grading, the GG genotype was significantly associated with higher ES grades (P=0.0076). Conclusions The PNPLA3 I148M GG genotype was not significantly associated with increased HCC occurrence in Korean MASLD patients within the present cohort. Although the GG genotype is known to play a role in development and progression of MASLD, further studies are warranted to clarify its contribution to tumor initiation and dedifferentiation.

Background and Objectives: Hearing loss significantly affects communication, psychosocial well-being, and quality of life. This study analyzes the National Health Insurance Service database to assess the trends and characteristics of hearing loss in South Korea from 2010 to 2020.Subjects and Method The database encompasses 97% of the Korean population, providing comprehensive data on medical history, prescriptions, and health examinations. The analysis used the World Health Organization’s ICD-10 definitions to categorize hearing loss types and examine their prevalence and incidence across various demographics over 11 years. Results: There was an overall annual increase of 4.62% in diagnosed cases of hearing loss, with the most significant rise among the elderly. The rate of increase accelerated from 3.32% between 2010 and 2014 to 6.49% between 2014 and 2020, corresponding with the improved hearing aid access facilitated by policy changes. Women showed a slightly higher increase than men. The data also indicated a consistent rise in abnormal hearing test results during health examinations, especially in older adults. Conclusion The study highlights an increasing trend in hearing loss diagnoses, driven by an aging population and enhanced detection facilitated by policy changes. These findings emphasize the need for continuous monitoring and targeted health policies to manage hearing loss effectively, offering valuable insights for global health management and policy development.

Background and Objectives: This study aims to analyze trends in hearing disability and the use of hearing rehabilitation devices (hearing aids and cochlear implants) in South Korea over the past 11 years (2010-2020) using data from the National Health Insurance Service (NHIS).Subjects and Method Data were extracted from the NHIS database, covering approximately 97% of the South Korean population. Patients diagnosed with hearing loss were classified using ICD-10 codes. The data were analyzed to determine trends in hearing disability, hearing aid prescriptions, and cochlear implant usage by age, gender, and types and causes of hearing loss. Results: The number of hearing disability patients increased from 170900 in 2010 to 362738 in 2020, with an annual growth rate of 7.95%. The highest increase was observed in the ≥60 age group, with an annual growth rate of 11.04%. Hearing aid prescriptions rose from 4966 in 2010 to 11974 in 2020, showing a 10.45% annual increase. Females showed a higher growth rate in both hearing disability and hearing aid prescriptions compared to males. Cochlear implant prescriptions also increased, particularly among older adults. Conclusion The study highlights a significant rise in hearing disability and the use of hearing aids and cochlear implants in South Korea, especially among the elderly. The findings underscore the importance of early diagnosis and intervention for hearing loss and the need for policy improvements to enhance accessibility and affordability of hearing rehabilitation services. Additional strategies are needed to ensure appropriate hearing rehabilitation for those not yet receiving adequate care.

Background: The effectiveness of intravenous tissue plasminogen activator (IV tPA) in patients with large-vessel occlusion (LVO) receiving endovascular treatment (EVT) for acute ischemic stroke (AIS) has been questioned. We investigated IV tPA effectiveness in real-world AIS patients, including those with intracranial LVO receiving EVT. Methods: We identified patients with AIS who presented to hospital with National Institutes of Health Stroke Scale ≥4 within 8 hours of symptom onset from the institutional stroke registry. The association of IV tPA use with effectiveness and safety outcomes was analyzed in overall enrolled AIS patients; LVO patients; and patients treated with EVT. The effect of IV tPA was assessed using multiple logistic regression. Results: Among the 654 patients meeting study entry criteria, 238 (36.4%) received IV tPA and 416 (63.6%) did not. Multiple logistic regression analysis and shift analysis revealed IV tPA was associated with improved outcomes in overall enrolled AIS population, LVO, and EVT-treated subgroups. Among EVT-treated patients, IV tPA was associated with higher likelihood of ambulatory or better outcome (modified Rankin Scale 0–3) with odds ratio of 1.95 (P=0.03). Conclusions In this real-world study, IV tPA use was associated with improved outcomes for patients with AIS, including among LVO patients treated and not treated with EVT, in the contemporary mechanical thrombectomy era.

Background: This study aimed to investigate the prevalence, management, and comorbidities of diabetes mellitus among Korean adults. Methods: Data from the Korea National Health and Nutrition Examination Survey (2019–2022) were analyzed to assess the prevalence, treatment, risk factors, and comorbidities of diabetes. Comparisons between young and older adults with diabetes were emphasized. Results: Among Korean adults aged ≥30 years, the prevalence of diabetes is 15.5% during 2021–2022. Of these, 74.7% were aware of their condition, 70.9% received antidiabetic treatment, and only 32.4% achieved glycosylated hemoglobin (HbA1c) <6.5%. Moreover, 15.9% met the integrated management targets, which included HbA1c <6.5%, blood pressure <140/85 mm Hg, and low-density lipoprotein cholesterol <100 mg/dL. In young adults aged 19 to 39 years, the prevalence of diabetes was 2.2%. Among them, 43.3% were aware of their condition, 34.6% received treatment, and 29.6% achieved HbA1c <6.5%. Obesity affected 87.1%, and 26.9% had both hypertension and hypercholesterolemia. Among adults aged ≥65 years, the prevalence of diabetes was 29.3%, with awareness, treatment, and control rates of 78.8%, 75.7%, and 31.2%, respectively. Integrated management targets (HbA1c <7.5%, hypertension, and lipids) were achieved by 40.1%. Conclusion Diabetes mellitus remains highly prevalent among Korean adults, with significant gaps in integrated glycemic, blood pressure, and lipid control. Older adults with diabetes show higher awareness and treatment rates but limited integrated management outcomes. Young adults with diabetes bear a significant burden of obesity and comorbidities, alongside low awareness and treatment rates. Therefore, early intervention programs, education, and strategies tailored to younger populations are urgently required.

Background: and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes. Methods: We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data. Results: Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4. Conclusion Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.