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.

Subarachnoid hemorrhage (SAH) is a stroke subtype with high mortality and poor functional outcomes. Prompt occlusion of a ruptured aneurysm at an early stage is crucial to prevent rebleeding, which can result in even higher mortality and more severe disabilities. The most critical initial decision in SAH management is the choice of treatment method with surgical clipping or endovascular coiling. We aimed to develop an evidence-based clinical guideline to select the optimal initial treatment in patients with SAH. We developed this guideline based on evidence from systematic reviews and meta-analyses via a de novo process. A systematic literature review was conducted across four databases (MEDLINE, Embase, Cochrane, and KoreaMed) to answer two population, intervention, comparison, outcome questions comparing clipping and coiling. The risk of bias was assessed using ROB 2.0 and the Newcastle-Ottawa Scale. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagrams and meta-analyses were generated for functional outcome and mortality. We included six randomized control trials (RCTs) and 58 observational studies. Meta-analysis of RCTs showed that coiling improved functional outcomes compared to clipping (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.86–0.97). No significant mortality difference was observed in RCTs (OR, 1.38; 95% CI, 0.91–2.09), but non-RCTs favored clipping for reduced mortality (OR, 0.77; 95% CI, 0.69–0.86). However, it is difficult to generalize these findings to all clinical situations, as patients with SAH have a highly variable clinical course. Final treatment decision should be tailored to the individual patient’s status, including aneurysm location, morphology, and the expertise available at the treatment center. Such decisions are best made by specialists such as a board-certified physician and should be explained to the patient and their caregivers, along with the rationale for selecting the most appropriate treatment at the given hospital. Korea has many certified endovascular neurosurgeons, cerebrovascular surgeons, and certified cerebrovascular centers. Proper selection of the most suitable treatment method by certified physicians and centers would greatly benefit patient outcomes and healthcare professionals.

Accurate and early identification of stroke and large vessel occlusion (LVO) in emergency settings is essential for improving patient outcomes and ensuring the efficient allocation of medical resources. This clinical practice guideline systematically reviews domestic and international literature and conducts meta-analyses to evaluate the utility and diagnostic accuracy of stroke assessment tools used in prehospital emergency medical services (EMS). We developed a guideline based on evidence from systematic reviews and meta-analyses via a de novo process. A systematic literature review was conducted to evaluate the usefulness of diagnostic EMS assessment tools for diagnosing stroke and LVO. Overall, 70 non-randomized control studies were selected for this study. A meta-analysis was conducted with a subgroup analysis to distinguish between patients with stroke and those with LVO. EMS tools demonstrated high sensitivity but low specificity for diagnosing stroke. In the prehospital setting, using validated EMS stroke assessment tools is recommended for the early identification of stroke and LVO. Upon hospital arrival, stroke specialists should conduct further evaluation and triage to confirm the diagnosis and guide appropriate management. Delays in diagnosing LVO are frequently unacceptable. While experts advocate for the use of EMS assessment tools to facilitate early identification of LVO, these tools alone lack adequate sensitivity. Therefore, further diagnostic evaluations and consultation with stroke specialists upon hospital arrival are recommended.

The mothership (MS) model, where patients are directly transferred to a thrombectomy-capable center, and the drip-and-ship (DS) model, where thrombolysis is initiated at the nearest primary stroke center before transfer for thrombectomy, are the primary transport modes for patients with stroke. We aimed to establish guidelines for selecting the appropriate transfer strategy based on emergent large vessel occlusion (LVO). We developed this guideline based on evidence from systematic reviews and meta-analyses via a de novo process. A systematic literature review was conducted across four databases (MEDLINE, Embase, Cochrane, and KoreaMed) to answer three Population, Intervention, Comparison, and Outcome questions comparing MS and DS models. The risk of bias was assessed using the Newcastle-Ottawa Scale. Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagrams and meta-analyses were generated for functional outcomes, mortality, and successful recanalization. Twenty-six non-randomized controlled studies showed that the MS model improved good functional outcomes by approximately 14% compared with the DS model (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.00–1.30). Fifteen studies reported that mortality in the MS and DS models showed no significant differences (OR, 0.97; 95% CI, 0.84–1.11). Twenty-four studies revealed no significant difference in successful recanalization between the MS and DS models (OR, 0.87; 95% CI, 0.68–1.10). The MS model should be considered first to improve the functional outcome of patients with LVO. However, if thrombectomy cannot be performed immediately after thrombolysis, or if a thrombectomy-enabled hospital is not nearby, the DS model should be considered by stroke specialists depending on transportation time and regional factors. We suggest a mixed approach with the DS model based on specific circumstances or regions to ensure the optimum treatment of patients with acute ischemic stroke (AIS). Appropriate transport for patients with LVO improves the prognosis of AIS.

BACKGROUND/OBJECTIVES: Particulate matter 2.5 (PM2.5) exposure can promote epithelialmesenchymal transition (EMT) in human retinal pigment epithelial (RPE) cells. The flowers of Tagetes erecta Linn, commonly known as marigold, are rich in diverse flavonoids and carotenoids and play a significant role in preventing cellular damage induced by oxidative stress, but the role of their extracts in RPE cells has not been reported. This study aimed to evaluate the influence of an ethanol extract of T. erecta Linn flower (TE) on PM2.5-induced EMT processes in RPE ARPE-19 cells.MATERIALS/METHODS: To investigate the protective effect of TE against ARPE-19 cell damage following PM2.5 treatment, cells were exposed to TE for 1 h before exposure to PM2.5 for 24 h. We investigated whether the efficacy of TE on suppressing PM2.5-induced EMT was related to antioxidant activity and the effect on the expression changes of factors involved in EMT regulation. Additionally, we further explored the role of intracellular signaling pathways associated with EMT inhibition. RESULTS: TE significantly blocked PM2.5-induced cytotoxicity while effectively preventing mitochondrial dysfunction, increased reactive oxygen species (ROS) generation, and mitochondrial membrane potential disruption. TE inhibited PM2.5-induced EMT and inflammatory response by suppressing the ROS-mediated transforming growth factor-β/ suppressor of mothers against decapentaplegic/mitogen-activated protein kinases signaling pathway. CONCLUSION Our results suggest that marigold extract is a highly effective in protection against PM2.5-induced eye damage.

Heart failure (HF) is a major cause of mortality and morbidity in South Korea, imposing substantial physical, emotional, and financial burdens on patients and society. Despite the high burden of symptom and complex care needs of HF patients, palliative care and hospice services remain underutilized in South Korea due to cultural, institutional, and knowledge-related barriers. This position statement from the Korean Society of Heart Failure emphasizes the need for integrating palliative and hospice care into HF management to improve quality of life and support holistic care for patients and their families. By clarifying the role of palliative care in HF and proposing practical referral criteria, this position statement aims to bridge the gap between HF and palliative care services in South Korea, ultimately improving patient-centered outcomes and aligning treatment with the goals and values of HF patients.

Purpose: This study aimed to define an optimal age cutoff for early-onset gastric cancer (EOGC) and compare its characteristics with those of late-onset gastric cancer (LOGC) using nationwide survey data. Methods: Using data from a nationwide survey, this comprehensive population-based study analyzed data spanning 3 years (2009, 2014, and 2019). The joinpoint analysis and interrupted time series (ITS) methodology were employed to identify age cutoffs for EOGC based on the sex ratio and tumor histology. Clinicopathologic characteristics and surgical outcomes were compared between the EOGC and LOGC groups. Results: The age cutoff for defining EOGC was suggested to be 50 years, supported by joinpoint and ITS analyses. Early gastric cancer was predominantly present in the EOGC and LOGC groups. Patients with EOGC comprised 20.3% of the total study cohort and demonstrated a more advanced disease stage compared to patients with LOGC. However, patients with EOGC underwent more minimally invasive surgeries, experienced shorter hospital stays, and had lower postoperative morbidity and mortality rates. Conclusion This study proposes an age of ≤50 years as a criterion for defining EOGC and highlights its features compared to LOGC. Further research using this criterion should guide tailored treatment strategies and improve outcomes for young patients with gastric cancer.

Purpose: Multidisciplinary treatment (MDT) in gastric cancer is an effective approach for establishing treatment plans.However, the appropriateness of using “ratio of MDT” as an item for evaluating the adequacy of gastric cancer treatment in Korea has not been previously researched. The purpose of this study is to verify whether the “ratio of MDT” is appropriate as an item for gastric cancer adequacy evaluation from the surgeon’s perspective. Methods: This study involved 142 patients who received MDT at our hospital between December 2015 and January 2023.Patients were divided into 2 groups based on the date when gastric cancer adequacy evaluation was implemented; there were 71 patients before and after the evaluation was conducted, respectively. Based on electronic medical records, the initial plan prepared before the MDT clinic and the final plan prepared after the clinic were compared to determine whether the plan was changed. Results: The average age of patients who received MDT before and after the evaluation was 64.8 and 62.2 years, respectively. Overall, 50 and 21 patients were male (70.4%) and female (29.6%), respectively, in both groups. Before the evaluation, 26 patients (36.6%) who received MDT changed their treatment plans after visiting the clinic, and 15 patients (21.1%) who received MDT after the evaluation had their treatment plans modified. Groups who received MDT and changes in treatment plans were significantly correlated (P = 0.042). Conclusion Our findings suggest that including the “ratio of MDT” as an item of gastric cancer adequacy evaluation needs reassessment.