Purpose: Limited treatment options exist for patients with metastatic castration-resistant prostate cancer (mCRPC) after the failure of taxane-based chemotherapy and novel hormonal therapy. Here, we report the safety and efficacy of ifosfamide and mesna in patients with mCRPC after the failure of taxane-based chemotherapy and novel hormonal therapy (NCT06236789). Materials and Methods: Patients with histologically confirmed prostate cancer who had failed taxane-based chemotherapy and novel hormonal therapy received ifosfamide 2,500 mg/m2 and mesna 1,500 mg/m2 on days 1–3, repeated every 21 days. Safety, objective response rate, disease control rate, reduction in serum prostate-specific antigen (PSA) concentration by >50% (PSA50) or >90% (PSA90), radiographic progression-free survival (rPFS), and overall survival (OS) were analyzed. Results: A total of 47 patients with mCRPC were included in the study. The median number of lines of treatment was 5 (range, 3 to 7). All patients were previously administered docetaxel and novel hormonal therapies including abiraterone (51.1%) and/or enzalutamide (61.7%). Thirty-eight patients (80.9%) were administered cabazitaxel. The objective response and disease control rates were 21.3% and 80.9%, respectively. PSA50 and PSA90 were achieved in 31.9% and 10.6%, respectively. During a median follow-up duration of 54.3 months, rPFS and OS were 5.0 and 9.0 months, respectively. All the patients experienced treatment-related adverse events of any grades; however, no new safety signs were detected. Genomic biomarker analysis revealed that alterations in the TP53 pathway were associated with inferior rPFS and OS. Conclusion Ifosfamide and mesna showed appreciable efficacy and manageable safety profiles in heavily treated patients with mCRPC.

Limited data exist regarding the real-world practices and clinical outcomes in patients with ischemic heart failure with reduced left ventricular ejection fractions (LVEFs).Using nationwide registry data from South Korea, we aimed to investigate long-term outcomes and clinical practices, especially implantable cardioverter defibrillators (ICDs) implantation, in patients with reduced LVEFs at least 40 days after acute myocardial infarction (AMI). Of 13,056 patients with AMI between 2011 and 2015, we analyzed 350 (median age, 66 years [interquartile range, 56-75]) who had LVEFs <40% on follow-up transthoracic echocardiogram 40 days after the index event. The primary outcome was cardiac-cause mortality at 3 years. Secondary outcomes comprised major cardiovascular events as well as outcomes defined by the use of ICDs, cardiac resynchronization therapy defibrillators (CRT-Ds), and electrophysiology studies. Among 350 patients, 39 (11.1%) died from cardiac causes during 3 years of follow-up. Eleven (3.1%) were hospitalized for ventricular tachycardia. The rate of ICD or CRT-D implantation up to 3 years was 5.7% (20/350). Cox time-to-event analysis revealed older age, LVEF <30%, diabetes mellitus, and previous MI or revascularization as positively associated with cardiac death, whereas the use of statins and body weight <67 kg were negatively associated. This nationwide Korean registry demonstrated that only 5.7% of patients who had reduced LVEFs after 40 days of AMI underwent ICD implantations over 3 years. Considering the high mortality, concerted efforts are needed to improve clinical outcomes for patients who may have been candidates for ICD implantation.

Objective: To examine the risk of cardiovascular disease (CVD) associated with use of tumor necrosis factor inhibitors (TNFi) in patients with ankylosing spondylitis (AS). Methods: This study used data from the Korean National Health Insurance database. Patients aged ≥18 years who were newly diagnosed with AS between 2010 and 2018 and did not suffer prior CVD were included. The primary outcome was a composite endpoint of myocardial infarction (MI) or stroke. The secondary outcomes were specific endpoints of MI, stroke, or congestive heart failure. TNFi use was evaluated as a time-dependent variable. Cox proportional hazard regression was used to examine the association between TNFi use and risk of incident CVD. Results: Of 19,775 patients (mean age, 36.1 years; 75% male), 5,978 (30.2%) were exposed to TNFi treatment during the study period. During a follow-up of 4.8 (interquartile range, 2.9~7.2) years, 522 events of MI or stroke occurred. TNFi use was associated with a lower risk of MI or stroke than no TNFi use after adjusting for traditional CV risk factors and medications (adjusted hazard ratio [aHR], 0.72; 95% confidence interval [CI], 0.55~0.94). The lower risk of MI or stroke associated with TNFi use was consistently observed across subgroups. Risk of congestive heart failure did not differ between users and non-users of TNFi (aHR, 0.94; 95% CI, 0.75~1.18). Conclusion In a real-world AS cohort, TNFi treatment was associated with a reduced risk of atherosclerotic CVD. However, TNFi use was not associated with risk of congestive heart failure.

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.

Objective: To explain process of developing basic veterinary clinical performance guidelines, based on frequently observable clinical manifestations, thereby supporting competencybased veterinary education in Korea. Methods: A structured review of learning outcomes established by Korean Association of Veterinary Medical Colleges (KAVMC) was conducted by a planning committee including veterinary educators, practitioners, and advisory members. Owner-oriented descriptions were used to frame each performance task, and each was mapped to corresponding learning outcomes. These tasks were aligned with learning outcomes recommended by the KAVMC to support the development of communication, clinical reasoning, and performance-related competencies among veterinary students, thereby enhancing day-one clinical readiness. Results: In total, 63 clinical manifestations for a guidebook format that can be used for clinical education were identified and categorized by organ systems that are described in language understandable to animal owners. Conclusions and Relevance: The basic veterinary clinical performance guidelines based on common clinical manifestations would serve as a vital component in veterinary education to reinforce core graduation competencies.

BACKGROUND: Implant supporting materials are currently used in breast reconstruction. However, when used in humans, they are associated with several problems. To address these issues, a new mesh called TissueDerm was created by combining a collagen sponge with a 3D printed polycaprolactone (PCL) mesh. It has shown promising results in pig experiments and could potentially replace the most commonly used acellular dermal matrix (ADM) for breast reconstruction. METHODS: Four 12-month-old minipigs were used in this experiment. Silicone implants were wrapped with ADM or TissueDerm, and the breast tissue was excised and implanted along with the wrapped implants. Three months later, the minipigs were sacrificed and the skin and mammary gland tissue surrounding the implants were harvested for further analysis. Histological analyses and immunostaining were performed. RESULTS: Although there was no significant difference in capsule thickness between the ADM and TissueDerm groups, collagen was more involved in TissueDerm, leading to better tissue regeneration. TissueDerm also induced lower levels of inflammatory markers TNF-a and IL-6 compared to ADM. However, capsules induced with ADM had significantly higher collagen fiber alignment and alpha-smooth muscle actin (a-SMA) positive immunoreactivity, suggesting that TissueDerm may be less likely to cause spherical contractures in the porcine model compared to ADM. CONCLUSIONS The study found that TissueDerm has advantages over ADM in terms of easier tissue invasion and reduced spheroidization in a porcine model. The results showed that TissueDerm is a promising new mesh for implantbased breast reconstruction (IBBR) and could potentially replace ADM.

Background: Barriers to treatment with intravenous thrombolysis (IVT) for patients with acute ischemic stroke (AIS) in South Korea remain incompletely characterized. We analyze a nationwide prospective cohort to determine patient-level features associated with delayed presentation and non-treatment of potential IVT-eligible patients. Methods: We identified consecutive patients with AIS from 01/2011 to 08/2023 from a multicenter and prospective acute stroke registry in Korea. Patients were defined as IVT candidates if they presented within 4.5 hours from the last known well, had no lab evidence of coagulopathy, and had National Institute of Health Stroke Scale (NIHSS) ≥ 4. Multivariable generalized linear mixed regression models were used to investigate the associations between their characteristics and the IVT candidates or the use of IVT among the candidates. Results: Among 84,103 AIS patients, 41.0% were female, with a mean age of 69 ± 13 years and presentation NIHSS of 4 [interquartile range, 1–8]. Out of these patients, 13,757 (16.4%) were eligible for IVT, of whom 8,179 (59.5%) received IVT. Female sex (adjusted risk ratio [RR], 0.90; 95% confidence interval [CI], 0.86–0.94) and lower years of education (adjusted RR, 0.90; 95% CI, 0.84–0.97 for 0–3 years, compared to ≥ 13 years) were associated with a decreased likelihood of presenting as eligible for IVT after AIS; meanwhile, young age (adjusted RR, 1.12; 95% CI, 1.01–1.24 for ≤ 44 years, compared to 75–84 years) was associated with an increased likelihood of being an IVT candidate. Among those who were eligible for IVT, only age was significantly associated with the use of IVT (adjusted RR, 1.09; 95% CI, 1.03–1.16 for age 65–74 and adjusted RR, 0.83; 95% CI, 0.76–0.90 for ≥ 85 years, respectively). Conclusion Most patients with AIS present outside IVT eligibility in South Korea, and only 60% of eligible patients were ultimately treated. We identified increased age, female sex and lower education as key features on which to focus interventions for improving IVT utilization.

Background: Barriers to treatment with intravenous thrombolysis (IVT) for patients with acute ischemic stroke (AIS) in South Korea remain incompletely characterized. We analyze a nationwide prospective cohort to determine patient-level features associated with delayed presentation and non-treatment of potential IVT-eligible patients. Methods: We identified consecutive patients with AIS from 01/2011 to 08/2023 from a multicenter and prospective acute stroke registry in Korea. Patients were defined as IVT candidates if they presented within 4.5 hours from the last known well, had no lab evidence of coagulopathy, and had National Institute of Health Stroke Scale (NIHSS) ≥ 4. Multivariable generalized linear mixed regression models were used to investigate the associations between their characteristics and the IVT candidates or the use of IVT among the candidates. Results: Among 84,103 AIS patients, 41.0% were female, with a mean age of 69 ± 13 years and presentation NIHSS of 4 [interquartile range, 1–8]. Out of these patients, 13,757 (16.4%) were eligible for IVT, of whom 8,179 (59.5%) received IVT. Female sex (adjusted risk ratio [RR], 0.90; 95% confidence interval [CI], 0.86–0.94) and lower years of education (adjusted RR, 0.90; 95% CI, 0.84–0.97 for 0–3 years, compared to ≥ 13 years) were associated with a decreased likelihood of presenting as eligible for IVT after AIS; meanwhile, young age (adjusted RR, 1.12; 95% CI, 1.01–1.24 for ≤ 44 years, compared to 75–84 years) was associated with an increased likelihood of being an IVT candidate. Among those who were eligible for IVT, only age was significantly associated with the use of IVT (adjusted RR, 1.09; 95% CI, 1.03–1.16 for age 65–74 and adjusted RR, 0.83; 95% CI, 0.76–0.90 for ≥ 85 years, respectively). Conclusion Most patients with AIS present outside IVT eligibility in South Korea, and only 60% of eligible patients were ultimately treated. We identified increased age, female sex and lower education as key features on which to focus interventions for improving IVT utilization.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as blockbuster drugs for treating metabolic diseases. Glucagon-like peptide-1 (GLP-1) plays a pivotal role in glucose homeostasis by enhancing insulin secretion, suppressing glucagon release, delaying gastric emptying, and acting on the central nervous system to regulate satiation and satiety. This review summarizes the discovery of GLP-1 and the development of GLP-1RAs, with a particular focus on their central mechanisms of action. Human neuroimaging studies demonstrate that GLP-1RAs influence brain activity during food cognition, supporting a role in pre-ingestive satiation. Animal studies on hypothalamic feed-forward regulation of hunger suggest that cognitive hypothalamic mechanisms may also contribute to satiation control. We highlight the brain mechanisms of GLP-1RA-induced satiation and satiety, including cognitive impacts, with an emphasis on animal studies of hypothalamic glucagon-like peptide-1 receptor (GLP-1R) and GLP-1R-expressing neurons. Actions in non-hypothalamic regions are also discussed. Additionally, we review emerging combination drugs and oral GLP-1RA formulations aimed at improving efficacy and patient adherence. In conclusion, the dorsomedial hypothalamus (DMH)—a key GLP-1RA target—mediates pre-ingestive cognitive satiation, while other hypothalamic GLP-1R neurons regulate diverse aspects of feeding behavior, offering potential therapeutic targets for obesity treatment.