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.

Purpose: Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer, with approximately 30% of patients eventually developing brain metastases (BM), which result in poor outcomes. An understanding of the tumor microenvironment (TME) at both primary and metastatic sites offers insights into the mechanisms underlying BM and potential therapeutic targets. Materials and Methods: Spatial RNA sequencing (spRNA-seq) was performed on primary TNBC and paired BM tissues from three patients, one of whom had previously received immune checkpoint inhibitors before BM diagnosis. Specimen regions were categorized into tumor, proximal, and distal TME based on their spatial locations. Gene expression differences across these zones were analyzed, and immune cell infiltration was estimated using TIMER. A gene module analysis was conducted to identify key gene clusters associated with BM. Results: Distinct gene expression profiles were noted in the proximal and distal TMEs. In BM, the proximal TME exhibited neuronal gene expression, suggesting neuron-tumor interactions compared to tumor, and upregulation of epithelial genes compared to the distal TME. Immune cell analysis revealed dynamic changes in CD8+ T cells and macrophages across the tumor and TME zones. Gene module analysis identified five key modules, including one related to glycolysis, which correlated with patient survival. Drug repurposing analysis identified potential therapeutic targets, including VEGFA, RAC1, EGLN3, and CAMK1D. Conclusion This study provides novel insights into the transcriptional landscapes in TNBC BM using spRNA-seq, emphasizing the role of neuron-tumor interactions and immune dynamics. These findings suggest new therapeutic strategies and underscore the importance of further research.

Early neurologic deterioration (END) is common and occurs within a few hours to days after an ischemic stroke. Traditionally, END has been treated as a collective entity, including the occurrence of new deficits (recurrence) and the aggravation of pre-existing neurologic deficits (progression). END arises from distinct mechanisms that require different therapeutic approaches. We reviewed clinical and experimental studies addressing the epidemiology, mechanisms, and treatment of END, focusing on differentiating END due to recurrence from END due to progression and on interventions including antiplatelet therapy, direct thrombin inhibition, and induced hypertension. Early recurrence is closely associated with thrombus growth and new ischemic events, particularly in atherothrombotic disease. Early recurrence is also common in patients with cancer-associated stroke. Thrombin and platelet activation play central roles under both conditions. In contrast, progression is mainly driven by infarct growth, that is, the evolution from incomplete infarction to complete infarction due to impaired perfusion, especially in lesions involving the subcortical fiber tracts. Therapeutic implications differ accordingly. Recurrence may respond to potent antithrombotic strategies, including combined antiplatelet and direct thrombin inhibition, whereas progression may benefit from induced hypertension. However, recurrence and progression often occur simultaneously, making clinical differentiation challenging. END should be conceptualized as a spectrum of clinical presentations arising from distinct mechanisms. Recognizing recurrence and progression as separate processes is essential for mechanism-oriented treatments. Future trials should adopt this framework to develop individualized strategies and improve outcomes in patients with acute stroke.

Purpose: Atypical hyperplasia (AH) management remains controversial due to variable malignant disease progression rates. While Western studies report 10% to 25% upgrade rates, data from Asian populations, particularly from referral academic centers, are limited. We aimed to identify predictive factors for malignant upgrade in Korean women with AH at academic hospitals. Methods: This retrospective multi-institutional study analyzed 340 patients diagnosed with AH on initial biopsy who underwent subsequent excision at five Korean academic hospitals from 2000 to 2022. Malignant upgrade was defined as ductal carcinoma in situ or invasive cancer on the final pathology. Multivariate logistic regression was used to identify independent predictors of upgrades. Results: Among 340 patients (319 atypical ductal hyperplasia, 20 atypical lobular hyperplasia, and 1 mixed), 128 (37.6%) experienced a malignant upgrade, 98 (76.6%) to ductal carcinoma in situ, and 30 (23.4%) to invasive cancer. In multivariate analysis, multifocal atypia (odds ratio [OR], 25.61; 95% confidence interval [CI], 11.20–58.55; P<0.001) and Breast Imaging-Reporting and Data System 4c-5 lesions (OR, 11.02; 95% CI, 1.43–84.86; P=0.021) were significant predictors. Multifocal atypia showed an 84.4% upgrade rate. Core needle biopsy had higher upgrade rates than vacuum-assisted biopsy (45.2% vs. 20.0%; P<0.001). The upgrade rates decreased from 50% to 25% over the study period (P<0.05). Conclusion The 37.6% upgrade rate in this tertiary referral cohort exceeded that in Western reports, with multifocal atypia emerging as the strongest predictor. These findings support immediate excision for multifocal atypia while allowing individualized management for unifocal lesions with favorable imaging in Korean tertiary care settings.

Objective: This study aimed to find out the concordance between prescription and performance of neuropsychological tests inadults aged 90 and older. Methods: We analyzed 270 prescriptions of patients aged 90 and older from a single hospital between 2019 and 2025, retrospectively. Prescriptions included Seoul Neuropsychological Screening Battery-Second Edition (SNSB-II), Literacy Independent Cognitive Assessment (LICA), and Korean version of the Severe Impairment Battery (SIB-K). Administration outcomes wereclassified as concordant (as prescribed), substituted (to different battery administered), simplified (just screening test and clinicalinterview), or cancelled (not administered). Floor and ceiling effects were assessed in subtests and subscales of all tests. Results: Overall concordance rate was 52.2%. SNSB-II showed the lowest concordance (33.8%) and LICA demonstrated higher concordance (72.3%). SIB-K showed complete concordance (100%). SNSB-II completers had higher education levels thanLICA and SIB-K completers. Among subsets of SNSB-II, seven showed floor effects and three showed ceiling effects. LICA had floor effects in five and ceiling effect in one. In SIB-K, one showed floor effect and six showed ceiling effects. Conclusion LICA demonstrated good feasibility in this age group. These findings provide evidence for age-appropriate as-sessment protocols.

Objective: Perinatal depression often remains undertreated due to concerns about antidepressant exposure during fertility treatment, pregnancy, or breastfeeding. Non-pharmacological, home-based interventions such as transcranial direct current stimulation (tDCS) present a promising alternative; however, real-world evidence in perinatal populations remains limited. Methods: This prospective observational study included 38 women who received infertility, pregnancy, or postpartum treatment at four hospitals in South Korea. Participants self-administered anodal tDCS targeting the left dorsolateral prefrontal cortex for 20–28 sessions over 4 weeks. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D) at baseline and weeks 2, 4, and 8. Subjective health perception was measured at baseline using a 5-point Likert scale. Results: Time had a significant effect on depressive symptoms (Wald χ2=90.75, p<0.001), with the largest reduction observed during the first 2 weeks. The CES-D scores remained significantly lower than baseline at week 8, 4 weeks after treatment ended. Subjective health perception was significantly associated with baseline depression severity (Wald χ2=26.41, p<0.001), and its interaction with time was also significant (Wald χ2=320.18, p<0.001). Participants with poorer perceived health (scores 4–5) experienced greater depressive symptom reductions than those with more favorable perceptions (scores 1–2). Conclusion Home-based tDCS was feasible and associated with clinically meaningful improvement in depressive symptoms among perinatal women. Those who initially perceived their health more negatively showed greater response, suggesting subjective health perception may serve as a useful moderator and potential marker to inform personalized treatment strategies.

Background: The Act on Decisions on Life-Sustaining Treatment (LST) has been implemented in Korea since 2018, yet data on its application in neurocritical care units remain scarce. This study aimed to evaluate the clinical characteristics and outcomes of LST withdrawal or withholding in the neurocritical care unit. Methods: This study was a retrospective analysis conducted at a tertiary university hospital in Busan, South Korea. Among patients admitted to the neurocritical care unit between February 2018 and August 2023, those with documented decisions for LST withdrawal or withholding were enrolled. Demographic and clinical characteristics, underlying and combined conditions, reasons for LST decisions, measures taken, and time from LST withdrawal to death were extracted from medical records. Results: A total of 69 patients were included, with a median age of 67 years, and 38 (55%) were male. Cerebrovascular disease (62%) and traumatic brain injury (22%) were the most common underlying diagnoses. The primary reason for LST decisions was irreversible neurological damage (71%), followed by systemic complications (19%). Mechanical ventilation cessation (91%) and extubation (86%) were most frequently used measures for LST withdrawal. The median time from LST withdrawal to death was 22 minutes. Conclusions Our study demonstrates that LST decisions in the neurocritical care unit predominantly occur among patients with cerebrovascular disease or traumatic brain injury, mostly triggered by neurological deterioration. Most patients died shortly after withdrawal. These findings provide important insight into current LST withdrawal practices in neurocritical care and may assist clinical and ethical decision making in similar settings.

Purpose: This study was performed to compare clinical features and emergency department (ED) outcomes between children and adults with non‑typhoidal Salmonella (NTS) gastroenteritis in a single‑center cohort. Methods: We retrospectively reviewed electronic medical records of ED patients with stool multiplex polymerase chain reaction-confirmed NTS at CHA Bundang Medical Center from January 2016 through December 2021. Demographics, presentation, laboratory and imaging findings, microbiology, and treatments were abstracted. Primary outcomes were the high acuity (a Korean Triage and Acuity Scale level 1-2), ED length of stay, and disposition. Results: Of 189 patients, 134 were children and 55 adults. The children had fewer comorbidities (5.2% vs. 56.4%; P < 0.001) and high acuity (children, 0% vs. adults, 14.5%), shorter median ED length of stay (237.0 minutes [interquartile range, 188.0-336.0] vs. 360.0 minutes [335.0-569.0]; difference, 123.0 minutes [95% confidence interval, 85.0-328.0]; P < 0.001), and less frequent hospitalizations to the intensive care unit (children, 0% vs. adults, 14.5%; P < 0.001). Fever (94.8% vs. 63.6%) and hematochezia (37.3% vs. 0%) were more common in the children (Ps < 0.001), while adults had higher frequencies of abdominal pain (87.3% vs. 71.6%; P = 0.020) and enteritis/ileus on radiography (63.3% vs. 45.3%; P = 0.033), and higher median values of segmented white blood cells (79.0% vs. 69.4%; P = 0.010) and C‑reactive protein concentration (7.2 vs. 6.3mg/dL; P < 0.001). Ceftriaxone was more commonly used in the children (children, 72.7% vs. adults, 51.9%; P < 0.001). Conclusion Compared with the adults, the children with NTS gastroenteritis presented with lower clinical acuity, shorter ED stays, and no hospitalizations to the intensive care unit, despite more common fever and hematochezia. These findings may support a conservative ED approach in children with careful, indication‑based antibiotic use and highlight opportunities for antimicrobial stewardship.

Background/Aims: This study investigated the clinical efficacy of low-dose mepolizumab (100 mg) in controlling severe eosinophilic asthma, aiming to induce eosinophilic granulomatosis with polyangiitis (EGPA) remission and reduce systemic steroid usage. Additionally, we constructed a basic frame for our longitudinal EGPA cohort by collecting serial blood samples before, during, and after mepolizumab treatment in EGPA patients. Methods: We conducted a 2-year prospective observational cohort study in patients with uncontrolled severe eosinophilic asthma and refractory EGPA who used systemic steroids (≥ 7.5 mg/day of prednisolone) or other immunosuppressant drugs for at least 6 months. All patients were treated with 100 mg of mepolizumab every 4 weeks for 1 year to control severe eosinophilic asthma and then were followed for an additional 1 year to monitor their disease course. We analyzed total systemic steroid use and EGPA remission/relapse during the study period. Results: Three EGPA patients were included in this study and completed 16 study visits over a 2-year period. After 1 year of treatment with mepolizumab (100 mg monthly), all 3 patients were able to reduce their maintenance dose of systemic steroids, with 2 patients completely discontinuing use. These 2 patients achieved EGPA remission during mepolizumab treatment, and their remission status remained stable for 1 year after they stopped receiving the medication. Conclusions Low-dose mepolizumab treatment demonstrated clinical efficacy in reducing the maintenance dose of systemic steroids required for severe refractory EGPA. While not all patients achieved EGPA remission with low-dose mepolizumab, some did, and their remission persisted even after treatment discontinuation.

Background/Aims: Endoscopic anti-reflux therapy is a therapeutic option for gastroesophageal reflux disease (GERD), providing durable effects. However, clinical data from Korea remain limited. This study evaluates the clinical outcomes of endoscopic radiofrequency Stretta therapy in Korean patients. Methods: A retrospective analysis was conducted on 71 patients with GERD who underwent Stretta therapy at 2 tertiary hospitals in Korea between November 2015 and July 2021. Clinical outcomes, including patient satisfaction, medication cessation or reduction, and complications, were evaluated. Pre- and post-procedural esophageal manometry and 24-hour pH monitoring test results were also analyzed. Results: Patient satisfaction rates at 1, 6, and 12 months post-procedure were 54.7% (35/64), 70.0% (28/40), and 75.0% (21/28), respectively. Medication cessation or reduction was achieved in 31.2% (20/64) at 1 month, 70.0% (28/40) at 6 months, and 67.9% (19/28) at 12 months. Esophageal manometry (n = 21) showed no significant changes in mean lower esophageal sphincter pressure (18.7 mmHg [2.5-52.9] vs 17.4 mmHg [0.0-43.0], P = 0.702) or mean integrated relaxation pressure (8.2 mmHg [0.0-28.0] vs 10.1 mmHg [0.0-31.0], P = 0.840). The 24-hour pH monitoring (n = 18) demonstrated a nonsignificant decrease in acid exposure time (pH < 4) from 2.3% (0.0-8.4) to 1.6% (0.0-7.3) (P = 0.182). Similarly, the DeMeester score decreased non-significantly from 8.4 (0.8-27.7) to 6.6 (0.8-21.8) (P = 0.352). No procedure-related complications occurred. Conclusion Endoscopic radiofrequency Stretta therapy appears to be a safe treatment option for GERD and may provide favorable patient satisfaction and medication reduction.