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.

Objectives: . Differentiated thyroid cancer (DTC) has a favorable prognosis. However, indeterminate lymph nodes (LNs) are common, making it challenging to distinguish recurrent from persistent DTC. Previous studies have not specifically compared the prognosis between recurrent and persistent DTC. Therefore, we aimed to compare prognosis and oncologic characteristics between these two groups. Methods: . This retrospective cohort study was conducted at a single tertiary care institution and included 265 patients with DTC (recurrent, 109; persistent, 156) who underwent reoperation between November 1, 1999, and August 31, 2018, for structural disease. Patients with distant metastasis at the time of initial diagnosis were excluded. Clinical and oncological characteristics, patterns of LN metastasis, disease-free survival (DFS), and overall survival (OS) were compared between the two groups. For DFS, time zero was defined as the date of the second operation. Results: . Recurrent DTC had a higher incidence of central LN metastasis (P=0.003), infield recurrence (P<0.001), and distant metastasis (P<0.001). In contrast, persistent DTC more frequently exhibited lateral LN metastasis (P=0.003) and outfield recurrence (P<0.001). The most common site of neck LN metastasis was ipsilateral level VI/VII (51.4%) in recurrent DTC and ipsilateral level IV (43.0%) in persistent DTC. Ten-year DFS was significantly lower in recurrent DTC than in persistent DTC (41.0% vs. 67.9%; P<0.001). Recurrent DTC, older age, a higher number of metastatic LNs at the second operation (first reoperation), and R1/R2 resection at the second operation were associated with decreased DFS. OS did not significantly differ between recurrent and persistent DTC (P=0.160). Conclusion . Recurrent DTC is associated with poorer DFS than persistent DTC, although OS does not significantly differ between the two groups.

Objective: : A twig-like middle cerebral artery (T-MCA) is a rare condition characterized by steno-occlusion of the M1 segment of the middle cerebral artery (MCA) with nearby collateral arterial networks. Despite unclear pathophysiology, it is often classified as a congenital anomaly caused by failure of fusion of the plexiform MCA arterial plexus. We aimed to improve understanding of the pathophysiology of T-MCAs by analyzing incidental T-MCA findings and their natural history. Methods: : A retrospective chart review was performed between January 2011 and December 2023 at three medical centers treating both ischemic and hemorrhagic strokes. Patients with suspected MCA lesions were selected through radiology reports from computed tomography, magnetic resonance angiography, and digital subtraction imaging. Results: : We identified 51 T-MCA cases from a radiology report search spanning 13 years across three medical centers. The study included 9875 patients with ischemic stroke and 2097 with hemorrhagic stroke. Of the 51 T-MCA cases, incidental findings accounted for 25 (49.0%), ischemic stroke for 18 (35.3%), and hemorrhagic strokes accounted for eight cases (15.7%). T-MCA related ischemic and hemorrhagic strokes accounted for 0.18–0.38% of all strokes. The RNF213.R4810K mutation was identified in seven of 15 patients (46.7%) tested. We found three cases of a de-novo T-MCA that progressed from a normal MCA architecture. Conclusion : T-MCAs may represent an acquired secondary anomaly rather than a congenital lesion, followed by steno-occlusion of the focal MCA with new arterial network formation. Both Moyamoya angiopathy and chronic atherosclerosis likely contributed to disease progression. Formation of a microaneurysm, dilatation of the lenticulostriate artery, and hemodynamic stress can lead to stroke.

INTRODUCTION: Randomised controlled trials (RCTs) have informed guideline recommendations for the management of stable coronary artery disease (CAD). However, the real-world impact of contemporary guidelines and trials on practising physicians in the Asia-Pacific region remains uncertain. We aimed to evaluate the knowledge, attitudes and practices among cardiovascular physicians in the region regarding stable CAD management. METHOD: An anonymised cross-sectional electronic survey was administered to cardiovascular practitioners from the Asia Pacific, assessing 3 domains: 1) baseline knowledge on recent trials and society guideline, 2) attitudes towards stable CAD, and 3) case scenarios reflecting management preferences. Correlations among knowledge, attitudes and practice scores were assessed between physicians from developed and developing countries using Pearson correlation. RESULTS: Overall, 713 respondents from 21 countries completed the survey. The mean knowledge score was 2.90±1.18 (out of 4), with 37.3% of respondents answering all questions correctly, while 74.6% noted that guidelines have significant impact on their practice. Despite guidelines recommending optimal medical therapy, majority chose revascularisation (range 53.4- 90.6%) as the preferred strategy for the case scenarios. Practitioners from developed regions had higher knowledge scores and lower attitude scores compared to developing regions, while practice scores were similar in both groups. Weakly positive correlations were noted between knowledge, attitude and practice scores. CONCLUSION Variations exist in knowledge and attitudes towards guideline recommendations and correspondingly actual clinical practice in the Asia Pacific, with most practitioners choosing an upfront invasive strategy for the treatment of stable CAD. These differences reflect real-world disparities in guideline interpretation and clinical adoption.
Humans ; Coronary Artery Disease/therapy* ; Cross-Sectional Studies ; Practice Patterns, Physicians'/statistics & numerical data* ; Asia ; Health Knowledge, Attitudes, Practice ; Surveys and Questionnaires ; Male ; Practice Guidelines as Topic ; Female ; Attitude of Health Personnel ; Middle Aged ; Developing Countries

Objective: In this study, changes in treatment methods and patient prognosis were analyzed using a Korean nationwide medical insurance information database. Methods: Patients with subarachnoid hemorrhage who received surgical treatment for cerebral aneurysm from 2005 to 2020 were included. The specific surgery type was classified using the surgical code and according to whether stents were used. Yearly trends in mortality rates and poor prognosis, using tracheostomy as proxy, were analyzed by a simple regression analysis. A multistep logistic regression analysis was performed to evaluate the risk factors of mortality and poor prognosis. Results: Overall, 83,587 patients were included. Females were predominant (64.5%). Microsurgical clip usage rate decreased by approximately two-thirds from 78.8% in 2005 to 24.4% in 2020. Contrarily, endovascular treatment proportion gradually increased, and stent-assisted coil embolization rate surpassed microsurgical clip usage rate in 2020 (24.6% vs. 24.4%). In the multivariate analysis, endovascular treatment correlated positively with 3-month mortality (hazard ratio [HR]: 1.13, 95% confidence interval [CI]: 1.07–1.19, P<0.0001), although correlated negatively with poor prognosis (tracheostomy) (HR: 0.93, 95% CI: 0.89–0.98, P=0.0050). Conclusions According to the treatment trend analysis, during the 16 years studied, for patients with subarachnoid hemorrhage due to ruptured cerebral aneurysm, the endovascular treatment rate increased rapidly and stent-assisted coil embolization rate surpassed that of microsurgical clip ligation. Diversification of treatment methods has led to a decrease in mortality and improved prognosis.

Objective: In this study, changes in treatment methods and patient prognosis were analyzed using a Korean nationwide medical insurance information database. Methods: Patients with subarachnoid hemorrhage who received surgical treatment for cerebral aneurysm from 2005 to 2020 were included. The specific surgery type was classified using the surgical code and according to whether stents were used. Yearly trends in mortality rates and poor prognosis, using tracheostomy as proxy, were analyzed by a simple regression analysis. A multistep logistic regression analysis was performed to evaluate the risk factors of mortality and poor prognosis. Results: Overall, 83,587 patients were included. Females were predominant (64.5%). Microsurgical clip usage rate decreased by approximately two-thirds from 78.8% in 2005 to 24.4% in 2020. Contrarily, endovascular treatment proportion gradually increased, and stent-assisted coil embolization rate surpassed microsurgical clip usage rate in 2020 (24.6% vs. 24.4%). In the multivariate analysis, endovascular treatment correlated positively with 3-month mortality (hazard ratio [HR]: 1.13, 95% confidence interval [CI]: 1.07–1.19, P<0.0001), although correlated negatively with poor prognosis (tracheostomy) (HR: 0.93, 95% CI: 0.89–0.98, P=0.0050). Conclusions According to the treatment trend analysis, during the 16 years studied, for patients with subarachnoid hemorrhage due to ruptured cerebral aneurysm, the endovascular treatment rate increased rapidly and stent-assisted coil embolization rate surpassed that of microsurgical clip ligation. Diversification of treatment methods has led to a decrease in mortality and improved prognosis.

Purpose: This study aimed to evaluate and optimize microbial DNA extraction methods from urine, a non-invasive sample source, to enhance DNA quality, purity, and reliability for urinary microbiome research and biomarker discovery in bladder cancer. Materials and Methods: A total of 302 individuals (258 with genitourinary cancers and 44 with benign urologic diseases) participated in this study. Urine samples were collected via sterile catheterization, resulting in 445 vials for microbial analysis. DNA extraction was performed using three protocols: the standard protocol (SP), water dilution protocol (WDP), and chelation-assisted protocol (CAP). DNA quality (concentration, purity, and contamination levels) was assessed using NanoDrop spectrophotometry.Microbial analysis was conducted on 138 samples (108 cancerous and 30 benign) using 16S rRNA sequencing. Prior to sequencing on the Illumina MiSeq platform, Victor 3 fluorometry was used for validation. Results: WDP outperformed other methods, achieving significantly higher 260/280 and 260/230 ratios, indicating superior DNA purity and reduced contamination, while maintaining reliable DNA yields. CAP was excluded due to poor performance across all metrics. Microbial abundance was significantly higher in WDP-extracted samples (p<0.0001), whereas SP demonstrated higher alpha diversity indices (p<0.01), likely due to improved detection of low-abundance taxa. Beta diversity analysis showed no significant compositional differences between SP and WDP (p=1.0), supporting the reliability of WDP for microbiome research. Conclusions WDP is a highly effective and reliable method for microbial DNA extraction from urine, ensuring high-quality and reproducible results. Future research should address sample variability and crystal precipitation to further refine microbiome-based diagnostics and therapeutics.

Objective: In this study, changes in treatment methods and patient prognosis were analyzed using a Korean nationwide medical insurance information database. Methods: Patients with subarachnoid hemorrhage who received surgical treatment for cerebral aneurysm from 2005 to 2020 were included. The specific surgery type was classified using the surgical code and according to whether stents were used. Yearly trends in mortality rates and poor prognosis, using tracheostomy as proxy, were analyzed by a simple regression analysis. A multistep logistic regression analysis was performed to evaluate the risk factors of mortality and poor prognosis. Results: Overall, 83,587 patients were included. Females were predominant (64.5%). Microsurgical clip usage rate decreased by approximately two-thirds from 78.8% in 2005 to 24.4% in 2020. Contrarily, endovascular treatment proportion gradually increased, and stent-assisted coil embolization rate surpassed microsurgical clip usage rate in 2020 (24.6% vs. 24.4%). In the multivariate analysis, endovascular treatment correlated positively with 3-month mortality (hazard ratio [HR]: 1.13, 95% confidence interval [CI]: 1.07–1.19, P<0.0001), although correlated negatively with poor prognosis (tracheostomy) (HR: 0.93, 95% CI: 0.89–0.98, P=0.0050). Conclusions According to the treatment trend analysis, during the 16 years studied, for patients with subarachnoid hemorrhage due to ruptured cerebral aneurysm, the endovascular treatment rate increased rapidly and stent-assisted coil embolization rate surpassed that of microsurgical clip ligation. Diversification of treatment methods has led to a decrease in mortality and improved prognosis.

Background and Objectives: To analyze the clinical trends and treatment patterns of thyroid cancer in the recent decade in South Korea. Materials and Methods: Two distinctive datasets, a single institutional database from 2009 to 2021 of differentiated thyroid cancer (DTC) patients (n=3145) and a nationwide database of the Korean Cancer Center Registry (KCCR) from 2005 to 2019 for patients (n=414,828) with all types of thyroid cancer, were analyzed. Annual incidence, the extent of thyroidectomy and neck dissection, T and N stages, and postoperative radioactive iodine (RAI) were investigated and descriptively presented. Results: The institutional database demonstrated that the annual cases of DTC surgeries suddenly dropped in 2014, coinciding with a social debate on overdiagnosis in South Korea. Due to changes in the staging manual and management guidelines during the study period, lobectomy has been preferred more than total thyroidectomy and the number of anterior compartment neck dissections has decreased. However, cases with lateral neck dissection and T4 stage gradually increased, suggesting that social issue did not influence the incidence of advanced thyroid diseases. The KCCR database also supported a similar phenomenon that showed a recent increase in localized and regional disease after a shock from social controversy. Conclusion Our institutional and KCCR data findings collectively indicate a steady incidence in localized and regional thyroid cancer after the initial drop triggered by the 2014 controversy in South Korea.

Objective: : The treatment paradigm for acute ischemic stroke has undergone several major changes in the past decade, contributing to improved patient prognosis in clinical practice. However, the extent to which these changes have affected patient prognosis in the real-world is yet to be clarified. This study aimed to evaluate the real-world impact of modern reperfusion therapy for acute ischemic stroke using data from the National Health Insurance Service in Korea. Methods: : This study included patients aged 18–80 years who were admitted via the emergency room with an I63 code between 2011 and 2020. The rates of intravenous thrombolysis use and endovascular treatment according to the year of admission were investigated. Furthermore, the rates of decompressive craniectomy and 3-month mortality were also analyzed. The 10-year observational period was divided into three periods based on the 2015 guideline change as follows : prior, 2011–2014; transitional, 2015–2016; and modern, 2017–2020. Results: : A total of 307117 patients (mean age, 65.7±10.9 years) were included, and most patients were male (59.7%). The rate of endovascular treatment gradually increased during the study period from 0.71% in the prior period to 1.32% in the transitional period and finally to 1.85% in the modern period. Meanwhile, the 3-month mortality rate gradually decreased from 4.78% in the prior period to 4.03% in the transitional period and to 3.71% in the modern period. Conclusion : In Korea, the mortality rate decreased as the rate of modern reperfusion therapy increased in patients with acute ischemic stroke. Overall, technical and scientific advances in reperfusion therapy have improved the outcome of patients with acute ischemic stroke in Korea.