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.

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.

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: 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.

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.

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.

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.

Background: Coronavirus disease 2019 (COVID-19) is known to have a high incidence of loss of smell and taste. However, studies in the early stages of the COVID-19 pandemic have evaluated these symptoms using subjective surveys and simple olfactory tests only. Hence, we compared the olfactory and gustatory characteristics of patient groups with COVID-19 olfactory dysfunction (C19OD) and non-COVID-19 postinfectious olfactory dysfunction (PIOD) using an objective olfactory test and evaluated the significance of olfactory training in both patient groups. Methods: We retrospectively analyzed the medical records of 14 patients with a decreased sense of smell after having positive COVID-19 polymerase chain reaction results, and 56 patients with PIOD with no history of confirmed COVID-19. Participants were evaluated using the Korean version of the Sniffin’ stick (KVSS) II, and chemical gustometry and olfactory training was assessed during their first visit. Olfactory training was then re-evaluated after an average of 8 (± 6) weeks. Results: The average age of participants in the C19OD group was lower than in those in the non-COVID-19 PIOD group. The proportion of men in the C19OD group was higher than in the non-COVID-19 PIOD group. At baseline assessment, the C19OD group had better olfactory and gustatory functions. After olfactory training, the non-COVID-19 PIOD patient group showed a significant increase in all KVSS II Total, T, D, and I scores, but there was a non-significant increase in all scores in the C19OD group. Conclusion The C19OD group had better olfactory and gustatory function than the nonCOVID-19 PIOD group at the initial assessment. After olfactory training, there was an increase in olfactory function test scores in both groups. Olfactory training may be helpful in C19OD, as in non-COVID-19 PIOD.

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder characterized by uncontrolled terminal complement activation. Eculizumab, a monoclonal antibody C5 inhibitor was introduced in Korea in 2009 and has been the standard treatment option for PNH. Methods: This study assessed the long-term efficacy/safety of eculizumab in PNH using real-world data from the Korean Health Insurance Review and Assessment Service. Eighty patients who initiated eculizumab from 2009–2020 were enrolled. Results: At eculizumab initiation, the median age was 51.5 years, lactate dehydrogenase (LDH) 6.8 × upper limit of normal, and granulocyte clone size 93.0%. All patients had at least one PNH-related complication before eculizumab initiation, including renal failure (n = 36), smooth muscle spasm (n = 24), thromboembolism (n = 20), and pulmonary hypertension (n = 15). The median (range) duration of eculizumab treatment was 52.7 (1.0, 127.3) months (338.6 total treated patient-years). Despite high disease activity in the study population before treatment initiation, overall survival was 96.2% and LDH levels were stabilized in most patients during treatment. PNH-related complications at treatment initiation were resolved in 44.4% of patients with renal failure, 95.8% with smooth muscle spasm, 70.0% with thromboembolism, and 26.7% with pulmonary hypertension. Extravascular hemolysis occurred in 28.8% of patients (n = 23; 0.09 per patient-year) and breakthrough hemolysis in 18.8% (n = 15; 0.06 per patient-year). No treatment discontinuation cases related to eculizumab were observed. Conclusion These data provided evidence for the long-term efficacy and safety of eculizumab in Korean PNH patients with high disease burdens.