Conventional aryl hydrocarbon receptor (AhR) antagonists, which play a critical role in modulating tumor immune evasion, have shown limited clinical translation due to poor solubility, restricted systemic exposure, and dose-limiting toxicities. To overcome these limitations, we developed SB5794, a phosphate prodrug of the potent AhR antagonist SB2617, designed to improve aqueous solubility and pharmacokinetic properties. SB5794 exhibited markedly enhanced solubility and achieved more than six-fold higher systemic exposure in mice compared with SB2617, while fully retaining its in vitro AhR antagonistic activity. In syngeneic tumor models, SB5794 significantly inhibited tumor growth, and its combination with anti–PD-1 therapy further enhanced antitumor efficacy. However, repeated-dose studies revealed dose-dependent histopathological changes in the gastrointestinal tract, liver, and immune organs. Collectively, these findings demonstrate that SB5794 possesses improved drug-like properties and strong immunomodulatory activity, supporting its potential as a next-generation AhR-targeted immunotherapeutic candidate.

Purpose: Radiotherapy is used to reduce the risk of breast cancer recurrence after surgery, but it is a potential cause of secondary cancer. We validated the risk of secondary cancer in primary breast cancer who received radiotherapy compared with those who did not from a matched cohort using a large-scale observational study of the Observational Health Data Sciences and Informatics (OHDSI) data network. Materials and Methods: A retrospective comparative cohort study using propensity score-matched cohorts was performed using two Observational Medical Outcome Partnership common data model databases, from tertiary general hospitals in South Korea. Among female patients who underwent surgery after the diagnosis of breast cancer, the risk of secondary primary malignant occurrence after 1:1 matching was analyzed. Results: Among 27,078 patients with breast cancer, there was no significant difference in the risk of secondary cancer following radiotherapy in 4,426 patients after 1:1 propensity-score matching. Further, there were no significant differences in the sensitivity analysis according to age, latency period, and number of radiation treatments. Conclusion There was no difference in the risk of secondary cancer in the patients diagnosed with breast cancer depending on whether or not radiotherapy was performed after surgery. In the future, it is necessary to analyze including data generated during cancer treatment.

Purpose: Sentinel lymph node biopsy (SLNB) using dye and isotope (DUAL) is recommended over the dye-only (DYE) method after neoadjuvant chemotherapy (NCT) due to potentially lower false-negative rates. However, the long-term outcome of either method is unclear. We aimed to compare the long-term oncological outcomes of DYE versus DUAL SLNB methods in patients who received NCT. Materials and Methods: In this retrospective cohort study, 893 patients who underwent SLNB following NCT and had pathologically negative lymph nodes were included. After propensity score matching for cT, cN, and pT categories, 280 patients were in the DYE group and 560 in the DUAL group. Indigo carmine was used for dye and Tc-99m antimony trisulfate for isotope mapping. Results: Median follow-up was 75.6 months in the DYE group and 83.0 months in the DUAL group. Mean (±standard deviation) number of harvested sentinel nodes was 6.7 (±3.9) and 6.7 (±3.3) in the DYE and DUAL groups (p=0.875). Five-year distant metastasisfree survival was 95.2% in DYE group and 93.3% in DUAL group (hazard ratio [HR], 1.45; 95% confidence interval [CI], 0.82 to 2.57; p=0.192). Disease-free survival (HR, 0.97; 95% CI, 0.69 to 1.50; p=0.914) and overall survival (HR, 0.98; 95% CI, 0.56 to 1.69; p=0.954) were not significantly different. Axillary recurrence rate was 1.8% and 2.5% in DYE and DUAL groups (p=0.647). Conclusion Long-term oncological outcomes did not significantly differ between DYE and DUAL SLNB methods. The dye-only method can be safely recommended for breast cancer patients who received NCT.

Purpose: Langer's axillary arch (LAA) is a common muscular variant that may affect the assessment of axillary lymph nodes in breast cancer. We investigated whether the presence of the LAA had a meaningful clinical impact in a large cohort of Korean patients with breast cancer. Methods: The medical records and imaging of 2,904 patients (2,953 cases) who underwent axillary surgery for breast cancer were reviewed. The presence of LAA was determined using chest computed tomography scans. The number of retrieved lymph nodes, the accuracy of axillary ultrasonography, and survival outcomes were compared between the LAA and nonLAA groups. Results: The LAA muscle was identified in 301 patients (10.2%). Preoperative ultrasound evaluation showed a lower specificity in the LAA group (77.9% vs. 83.6%, p = 0.031).Additionally, invasive disease-free survival (iDFS) was significantly worse in the ‘LAA-positive patients’ after adjusting for stage, histologic grade, and treatment (adjusted hazard ratio, 2.00; 95% confidence interval, 1.00–4.01; p = 0.048), with regional axillary recurrence being notably more frequent in patients with the LAA muscle (p = 0.005). Conclusion The presence of the LAA muscle was associated with reduced specificity on preoperative ultrasound. Patients with LAA muscle-associated tumors had worse iDFS, with regional axillary recurrence occurring more frequently. Recognition of the LAA muscle during axillary staging and surgery may improve nodal assessment accuracy and outcomes, especially in the era of axillary surgery de-escalation.

Background: The ongoing medical crisis in Korea has severely impacted the operational environment of intensive care units (ICU), posing significant challenges to quality care for critically ill patients. This study aimed to evaluate the effects of the ongoing crisis on ICUs. Methods: A survey was conducted in July 2024 among intensivists in charge of ICUs at institutions accredited by the Korean Society of Critical Care Medicine for critical care. The survey compared data from January 2024 (pre-crisis) and June 2024 (post-crisis) on the number ICU beds, staffing composition, work hours, and the number and roles of nurse practitioners. Results: Among the total of 71 participating ICUs, 22 experienced a reduction in the number of operational beds, with a median decrease of six beds per unit, totaling 127 beds across these ICUs. The numbers of residents and interns decreased from an average of 2.3 to 0.1 per ICU, and the average weekly working hours of intensivists increased from 62.3 to 78.8 hours. Nurse practitioners helped fill staffing gaps, with their numbers rising from 150 to 242 across ICUs, and their scope of practice expanded accordingly. Conclusions The medical crisis has led to major changes in the critical care system, including staffing shortages, increased workloads, and an expanded role for nurse practitioners. This is a critical moment to foster interest and engage in active discussions aimed at creating a sustainable and resilient ICU system.

Objectives: People-centered care and social protection are critical for improving tuberculosis (TB) treatment outcomes. This study aimed to evaluate whether a vulnerability assessment tool, developed for an enhanced community-based care and management (ECCM) program in 2 Korean cities, could predict and improve final TB treatment outcomes based on patients’ vulnerability levels. Methods: Treatment outcomes in the ECCM group were compared with those in a control group, stratified by vulnerability level. During stage 1, one city served as the intervention region and the other as the control, with a crossover in stage 2. The vulnerability assessment included all notified patients with TB, and those identified as highly vulnerable in the intervention group received social support following a consultation with a case manager. Results: The vulnerability assessment tool demonstrated moderate predictive ability for unfavorable outcomes, with an area under the curve of 0.70 (95% confidence interval, 0.63 to 0.77). The patients with high vulnerability who received ECCM treatment demonstrated a 19.8-percentage point (%p) higher treatment success rate than the high vulnerability subcategory of the control group. ECCM also appeared to reduce loss to follow-up and TB-related mortality by 8.4%p and 7.3%p, respectively, although these findings should be interpreted with caution. Conclusions The results suggest that providing social support tailored to patient vulnerability at the time of diagnosis could improve TB treatment outcomes.

Yonsei University College of Medicine (YUCM) adopted a criterion-referenced assessment (CRA) system in 2014. Six cohorts have graduated over the past decade under CRA. Positive impacts on student wellness and academic achievement were observed during the system’s initial years, and this study therefore aimed to analyze the changing perceptions of graduating students who experienced CRA to reflect YUCM’s experience of CRA implementation and suggest future directions and insights. Utilizing self-reporting graduation survey data of 621 graduates from 2018 to 2023, eight items regarding perceptions of CRA were examined with analysis of variance to explore changes in perceptions among the graduates, and short answers were also reviewed to investigate keywords and main themes. The CRA grading system positively influenced students’ learning motivation, level of class participation, cooperative attitudes, and self-directed attitudes. In particular, students’ perceptions of cooperative attitudes significantly improved from 2018 (3.97) to 2023 (4.46). The system also had a positive impact on students’ interest in conducting research from 2018 (3.04) to 2023 (3.56). Students’ perceptions of validity significantly increased from 2018 (3.40) to 2023 (3.92), and the perceptions of reliability also increased from 2018 (3.38) to 2023 (3.65), although the inter-year changes were not statistically significant. This study on graduating students’ changing perceptions of the CRA at YUCM aligned with the intended goals and context of its introduction and implementation. Ongoing improvements in fairness and reliability are required to enhance students’ perceptions of the system’s credibility, necessitating ongoing education and improvement efforts. Further studies on the positive and negative factors influencing perceptions of CRA are required to derive insights for system improvement.

Background: In vitro and animal studies have demonstrated that bone morphogenetic protein-7 (BMP-7), renowned for its osteogenic properties, also exerts beneficial effects on muscle metabolism by enhancing myogenesis and reversing muscle atrophy. Despite being proposed as a common regulatory factor for both muscle and bone, the impact of BMP-7 on human muscle health has not been thoroughly investigated. Methods: This cross-sectional study involved 182 community-dwelling older adults who underwent a comprehensive geriatric assessment in South Korea. Sarcopenia was diagnosed using Asian-specific cutoffs, and serum BMP-7 levels were quantified via enzyme immunoassay. Results: The mean age of the participants was 72.2±7.3 years, with 62.6% being female. After adjustments for confounders, serum BMP-7 levels were not significantly different between individuals with and without sarcopenia, nor were there differences based on skeletal muscle mass, strength, or physical performance levels (p=0.423 to 0.681). Likewise, no correlations were detected between circulating BMP-7 levels and any sarcopenia assessment metrics such as skeletal muscle index, grip strength, gait speed, or chair stand completion times (p=0.127 to 0.577). No significant associations were observed between increases in serum BMP-7 concentrations and the risk of sarcopenia or poor muscle phenotypes (p=0.431 to 0.712). Stratifying participants into quartiles based on serum BMP-7 levels also indicated no differences in sarcopenia-related parameters (p=0.663 to 0.996). Conclusion Despite experimental evidence supporting BMP-7’s role in muscle metabolism, this study found no significant association between serum BMP-7 levels and clinical indicators of muscle health in older adults. These findings challenge the utility of serum BMP-7 as a biomarker for sarcopenia in this demographic.

Background: Sclerostin, initially recognized for its pivotal role in bone metabolism, has gained attention for its multifaceted impact on overall human health. However, its influence on frailty—a condition that best reflects biological age—has not been thoroughly investigated. Methods: We collected blood samples from 244 older adults who underwent comprehensive geriatric assessments. Sclerostin levels were quantified using an enzyme-linked immunosorbent assay. Frailty was assessed using two validated approaches: the phenotypic model by Fried and the deficit accumulation frailty index (FI) by Rockwood. Results: After controlling for sex, age, and body mass index, we found that serum sclerostin levels were significantly elevated in frail individuals compared to their robust counterparts (P<0.001). There was a positive correlation between serum sclerostin concentrations and the FI (P<0.001). Each standard deviation increase in serum sclerostin was associated with an odds ratio of 1.87 for frailty (P=0.003). Moreover, participants in the highest quartile of sclerostin levels had a significantly higher FI and a 9.91-fold increased odds of frailty compared to those in the lowest quartile (P=0.003 and P=0.039, respectively). Conclusion These findings, which for the first time explore the association between circulating sclerostin levels and frailty, have significant clinical implications, positioning sclerostin as one of potential blood-based biomarkers for frailty that captures the comprehensive physical, mental, and social aspects of the elderly, extending beyond its traditional role in bone metabolism.