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.

A 43-year-old woman presented with bilateral lower extremity weakness due to an intradural extramedullary spinal cord tumor. Surgery revealed Ewing sarcoma, a rare presentation known as primary intradural extramedullary Ewing sarcoma (PIEES). Despite initial treatment with radiation and chemotherapy, tumor recurrence occurred after 17 months. Further interventions included additional surgery, radiation, and chemotherapy. The disease progressed to leptomeningeal metastases along the spinal cord, prompting various treatments including targeted spinal radiation and systemic therapies. Brain metastases subsequently developed, necessitating whole-brain radiation and intrathecal chemotherapy. This case highlights the aggressive nature of PIEES, its potential for widespread leptomeningeal metastasis, and the challenges in its management, underscoring the need for multidisciplinary approaches in treating this rare and aggressive malignancy.

Purpose: This study aimed to investigate the impact of physical activity on dementia risk among cancer survivors in South Korea. Materials and Methods: This retrospective, population-based cohort study included 344,152 cancer survivors identified from the National Health Insurance Service database in South Korea. The mean follow-up time was 5.81 years. Different levels of physical activity post-cancer diagnosis, ranging from inactive to highly active, were assessed. The primary outcome was the incidence of overall dementia, Alzheimer’s disease, and vascular dementia. Secondary outcomes included dementia risk stratified by cancer type and treatment (chemotherapy and radiation). Results: Of the total participants, 24,363 (7.08%) developed dementia. The risk of overall dementia decreased sequentially across the exercise groups compared to the inactive group: insufficiently active (adjusted hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.86 to 0.92), active (adjusted HR, 0.85; 95% CI, 0.83 to 0.88), and highly active (adjusted HR, 0.79; 95% CI, 0.76 to 0.82). This inverse relationship between exercise and dementia risk was statistically significant across various cancer types and was consistent regardless of age, comorbidities, and whether or not excluding the first 1, 2 years. Conclusion Among cancer survivors in South Korea, increased physical activity post-diagnosis was associated with a significantly lower risk of dementia. These findings underscore the importance of promoting physical activity in cancer survivors for cognitive health.

Subglottic stenosis (SGS) and tracheal stenosis (TS) are rare conditions that can cause significant breathing difficulties and, if not properly managed, may lead to life-threatening complications. Despite their clinical importance, debate continues regarding the optimal management of adult SGS and TS, and no comprehensive guidelines have been established to date. The Korean Bronchoesophagological Society appointed a task force to develop clinical practice guidelines with the goal of providing evidence-based recommendations for managing SGS and TS in adults. The task force conducted a systematic review of the relevant literature by searching PubMed, Embase, and the Cochrane Library using predefined search terms aligned with key clinical questions. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, which also informed the formulation and reporting of the recommendations. The strength of each recommendation reflects the guideline panel’s confidence that the benefits of an intervention outweigh its risks for eligible patients. After drafting the guidelines, feedback was obtained through Delphi questionnaires completed by members of the Korean Bronchoesophagological Society. Ultimately, the committee developed 17 evidence-based recommendations across four categories: initial evaluation, medical management, surgical treatment, and postoperative management and rehabilitation. These guidelines aim to support clinicians in delivering optimal care to adult patients with SGS and TS.

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.

Disruptive behavior disorder (DBD), which includes oppositional defiant disorder and conduct disorder, is among the most common externalizing disorders in childhood and adolescence. This review aimed to identify evidence-based psychotherapies for DBD and summarize their empirical foundations and characteristics. We searched for randomized controlled trials and systematic reviews using PubMed, PsycINFO, and Google Scholar, focusing on major evidence-based guidelines from the National Institute for Health and Care Excellence (NICE), American Psychological Association (APA), and Agency for Healthcare Research and Quality (AHRQ). Six interventions demonstrated the strongest empirical support: Incredible Years, Triple P, Parent–Child Interaction Therapy, Parent Management Training–Oregon Model, Multisystemic Therapy, and Treatment Foster Care–Oregon Model. These programs share a behavioral foundation that emphasizes parent-centered interventions as the core therapeutic mechanism. Considering treatment resistance and legal implications, multisystemic and community-based approaches are recommended for adolescents with severe antisocial behavior. In Korea, existing studies have primarily applied cognitive-behavioral, child-focused, and group interventions with limited fidelity assessments and few parent-focused trials. Future priorities include disseminating and validating parent-based behavioral therapies, establishing longterm follow-up systems, and adapting digital or telehealth platforms to enhance accessibility. Strengthening evidence-based, scalable behavioral interventions is crucial for improving the outcomes of Korean youths with DBD.

Objective: To identify clinical factors associated with in-hospital mortality among patients presenting to the emergency department (ED) with nontraumatic myocardial injury. Methods: This retrospective observational study included adult patients who visited a single ED from January to December 2022 and had elevated high-sensitive troponin I levels above the 99th percentile. Patients with trauma, cardiac arrest, transfers, or do-not-resuscitate status were excluded. Data on the demographics, vital signs, mental status, comorbidities, and final ED diagnoses were analyzed using multivariable logistic regression analysis. Results: Among 989 patients, 117 (11.8%) died during hospitalization. The respiratory rate ≥25/min (adjusted odds ratio [aOR], 5.39; 95% confidence interval [CI], 1.65-6.59), respiratory rate 21-24/min (aOR, 3.30; 95% CI, 2.64-11.02), and SpO2 <91% (aOR, 5.47; 95% CI, 2.73-10.95) were significantly associated with mortality. Comorbidities, including coronary artery disease (aOR, 2.78; 95% CI, 1.47-5.26), respiratory disease (aOR, 2.89; 95% CI, 1.18-7.15), and malignancy (aOR, 2.91; 95% CI, 1.18-7.15), were also independent predictors. Compared to a type 1 myocardial infarction, the final ED diagnoses of infectious diseases (aOR, 31.88; 95% CI, 11.59-87.72), neoplasms (aOR, 6.71; 95% CI, 2.51-17.94), and cerebrovascular diseases (aOR, 4.76; 95% CI, 1.75-11.46) were associated with higher mortality. Conclusion In patients with nontraumatic myocardial injury presenting to the ED, respiratory abnormalities, coronary artery diseases, respiratory diseases and malignancy were independently associated with in-hospital mortality, while final ED diagnoses of infection, neoplasm, and cerebrovascular disease were associated with a higher risk of mortality compared to type 1 myocardial infarction.

Purpose: Radiotherapy (RT) remains a cornerstone of curative treatment for localized and locally advanced prostate cancer. However, dose escalation to improve tumor control is often constrained by the proximity of the rectum, which increases the risk of gastrointestinal (GI) and genitourinary toxicities. Biodegradable rectal spacers inserted between the prostate and rectum have emerged as an effective approach to reduce rectal radiation exposure. This guideline provides evidence-based recommendations on indications, contraindications, procedural standards, and clinical management for biodegradable rectal spacer insertion during prostate cancer RT. Materials and Methods: This guideline was developed by a multidisciplinary expert panel through a systematic review of the literature, analysis of international guidelines (National Comprehensive Cancer Network, European Association of Urology, American Society for Radiation Oncology), and expert consensus among radiation oncologists, radiologists, and urologists with clinical experience in spacer insertion. The strength of each recommendation and the level of evidence were classified according to the modified GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system. Results: Spacer insertion is conditionally recommended (Grade C, Level I) for patients receiving definitive external-beam RT without rectal invasion. It reduces the high-dose rectal irradiation volume (V70–75) by >50%, decreases acute GI toxicity, and helps maintain bowel-related quality of life. However, the benefit for late severe toxicity (grade 2 or higher) remains debated in recent meta-analyses. Contraindications include rectal invasion, anatomical inaccessibility, infection, and material hypersensitivity. Procedures should be performed under local anesthesia in a sterile environment by trained physicians. Short-course antibiotics and simulator-based training, including completion of multiple supervised cases, are advised. Conclusion Biodegradable rectal spacer insertion is clinically validated and effective in reducing acute rectal toxicity. Although pivotal trials demonstrated a favorable procedural safety profile, real-world postmarket data include reports of rare but severe procedural complications. This guideline provides standardized recommendations tailored to Korean clinical practice while remaining consistent with international standards, emphasizing the importance of operator training and careful patient selection.

Reconstructing Fournier’s gangrene is particularly challenging because it rapidly leads to soft tissue necrosis that requires extensive debridement. This often results in a large soft tissue defect with dead space due to structural irregularity. We report two cases of Fournier’s gangrene successfully reconstructed using a pedicled anterolateral thigh (ALT) flap with a chimeric pattern. A 61-year-old man with Fournier’s gangrene presented with extensive necrosis in the penoscrotal area. After radical debridement and infection control, the wound was reconstructed using a chimeric pattern pedicled ALT flap. The flap was composed of fasciocutaneous and muscle components supplied by branch vessels from the main pedicle. The fasciocutaneous component adequately resurfaced the defect, and the muscle component filled in the dead space between the two testes. A 58-year-old man with Fournier’s gangrene on the penoscrotal area also underwent reconstruction using the same method. In both cases, the flaps survived without any major complications and the reconstructions were successful with no recurrence of infection. When reconstructing Fournier’s gangrene, a trapezoidal-shaped dead space between the two testes is inevitable. Inadequate obliteration of this space may result in recurrent infection. An ALT flap with a chimeric pattern offers an adequate option for resurfacing and dead space obliteration.

Background: With the aging population and advancements in medical care worldwide, the number of older patients with end-stage kidney disease continues to rise. This study aimed to identify factors associated with osteoporosis and osteopenia in older patients undergoing incident hemodialysis and assess their impact on mortality. Methods: We analyzed a large multicenter retrospective cohort of patients aged ≥70 years undergoing incident hemodialysis to identify factors associated with osteoporosis using logistic regression analysis and to assess the association of death with osteoporosis and osteopenia using Cox multivariable analysis. Results: Among 710 patients, 39.0% and 19.6% had osteoporosis and osteopenia, respectively. Osteoporosis was significantly associated with female sex, a history of fractures, and the absence of phosphate binder use. During a median follow-up of 36.8 months, 348 participants (58.8%) died. Mortality rates were the highest in the osteoporosis group (79.8%), followed by the osteopenia (77.2%) and normal bone mineral density (BMD) groups (35.2%). Cox regression analysis revealed that even after adjusting for covariates, the osteoporosis group was significantly associated with a higher mortality risk than the normal BMD group. Osteoporosis at the start of hemodialysis was significantly associated with higher mortality. Conclusion We should consider the importance of bone health in patients undergoing incident hemodialysis and pay attention to the use of phosphate binders and fracture prevention.