BACKGROUND/OBJECTIVES: Isoflavones are estrogen-like compounds found in plants and their health effects remain equivocal. We investigated dietary isoflavone intake and its associated factors in Korean breast cancer survivors, with a comparison to cancer-free women. SUBJECTS/METHODS: The usual dietary intake of breast cancer survivors (n = 981, mean age 52 yrs) in 9 hospitals between 2012 and 2019 was assessed using 3-day food records or food frequency questionnaires (FFQs). They were age-matched to 2,943 cancer-free women who completed FFQs as part of a nationwide study conducted between 2012 and 2016. We used the flavonoid database of common Korean foods and the Phenol-Explorer database to estimate isoflavone intake. The contribution of each food or food group to the total isoflavone intake was calculated. The adjusted least-squares means of dietary isoflavone intake according to lifestyle and clinical factors were calculated using generalized linear models. RESULTS: Breast cancer survivors had a higher mean dietary isoflavone intake (23.59 mg/day) than cancer-free women (17.81 mg/day). Major food sources, including tofu, soybeans, and doenjang, contributed to over 70% of the isoflavone intake in both groups. When we estimated dietary isoflavone intake according to lifestyle characteristics, isoflavone intake increased with higher scores of adherence to the American Cancer Society dietary guidelines but decreased with increasing body mass index in both groups. Among cancer-free women, dietary isoflavone intake was higher among those who had never smoked and among dietary supplement users. Among breast cancer survivors, dietary isoflavone intakes did not vary with clinical characteristics, including time since surgery and estrogen receptor status. CONCLUSION Breast cancer survivors were more likely to consume isoflavones than agematched cancer-free women. Dietary isoflavone intake was associated with healthy lifestyle characteristics in women both with and without breast cancer. Further research is needed to understand the role of the higher isoflavone intake among breast cancer survivors compared to cancer-free women on their prognosis.

Background and Objectives: Evidence remains limited on the real-world prescription of very low-dose oral anticoagulation among frail patients with atrial fibrillation (AF). We described the practice patterns, effectiveness, and safety of very low-dose edoxaban (15 mg once daily). Methods: Patients with AF prescribed edoxaban 15 mg once daily in 2 tertiary hospitals between 2016 and September 2022 were included. Baseline clinical characteristics and clinical outcomes of interest were thromboembolic and bleeding events. Results: A total of 674 patients were included (mean age 78.3±9.1, 49.7% aged ≥80 years, 49.3% women, median follow-up 1.0±1.2 years). Mean CHA 2 DS 2 -VASc score was 3.9±1.6, and the modified HAS-BLED score was 2.0±1.1. Between 2016 and 2022, the number of very lowdose edoxaban prescriptions increased. The main reasons for the prescription of very lowdose were low body weight (55.5% below 60 kg), anaemia (62.8%), chronic kidney disease (40.2%), active cancer (15.3%), concomitant anti-platelet use (26.7%), and prior major bleeding (19.7%). During a median follow-up duration of 8 (interquartile range 3–16) months, overall thromboembolic and bleeding events occurred in 16 (2.3%) and 88 (13.1%) patients, respectively. Compared to the expected event rates on the established risk scoring systems, patients receiving very low-dose edoxaban demonstrated a 61% reduction in ischemic stroke, a 68% reduction of ischemic stroke/transient ischemic attack/systemic embolism, whereas a 49% increase in major bleeding. Conclusions The prescription of very low-dose edoxaban was increased over time, attributable to various clinical factors. The use of very low-dose edoxaban reduced the expected risk of thromboembolic events.

Background: We evaluated severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-specific humoral and cellular responses for up to 6 months after the 3rd dose of ancestral coronavirus disease 2019 (COVID-19) vaccination in people living with HIV (PLWH) and healthy controls (HCs) who were not infected with COVID-19. Methods: Anti-spike receptor-binding domain IgG (anti-RBD IgG) concentrations using chemiluminescence immunoassay and neutralizing antibodies using focus reduction neutralization test (FRNT) were assessed at 1 week after each dose of vaccination, and 3 and 6 months after the 3rd dose in 62 PLWH and 25 HCs. T-cell responses using intracellular cytokine stain were evaluated at 1 week before, and 1 week and 6 months after the 3rd dose. Results: At 1 week after the 3rd dose, adequate anti-RBD IgG (> 300 binding antibody unit /mL) was elicited in all PLWH except for one patient with 36 CD4 T-cell count/mm3 . The geometric mean titers of 50% FRNT against wild type (WT) and omicron BA.5 strains of SARS-CoV-2 in PLWH with CD4 T-cell count ≥ 500 cells/mm3(high CD4 recovery, HCDR) were comparable to HC, but they were significantly decreased in PLWH with CD4 T-cell count < 500/mm3 (low CD4 recovery, LCDR). After adjusting for age, gender, viral suppression, and number of preexisting comorbidities, CD4 T-cell counts < 500/mm3 significantly predicted a poor magnitude of neutralizing antibodies against WT, omicron BA.5, and XBB 1.5 strains among PLWH. Multivariable linear regression adjusting for age and gender revealed that LCDR was associated with reduced neutralizing activity (P = 0.017) and interferon-γ-producing T-cell responses (P = 0.049 for CD T-cell; P = 0.014 for CD8 T-cell) against WT, and strongly associated with more decreased cross-neutralization against omicron BA.5 strains (P < 0.001). Conclusion HCDR demonstrated robust humoral and cell-mediated immune responses after a booster dose of ancestral SARS-CoV-2 vaccine, whereas LCDR showed diminished immune responses against WT virus and more impaired cross-neutralization against omicron BA.5 strain.

Background: We evaluated severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-specific humoral and cellular responses for up to 6 months after the 3rd dose of ancestral coronavirus disease 2019 (COVID-19) vaccination in people living with HIV (PLWH) and healthy controls (HCs) who were not infected with COVID-19. Methods: Anti-spike receptor-binding domain IgG (anti-RBD IgG) concentrations using chemiluminescence immunoassay and neutralizing antibodies using focus reduction neutralization test (FRNT) were assessed at 1 week after each dose of vaccination, and 3 and 6 months after the 3rd dose in 62 PLWH and 25 HCs. T-cell responses using intracellular cytokine stain were evaluated at 1 week before, and 1 week and 6 months after the 3rd dose. Results: At 1 week after the 3rd dose, adequate anti-RBD IgG (> 300 binding antibody unit /mL) was elicited in all PLWH except for one patient with 36 CD4 T-cell count/mm3 . The geometric mean titers of 50% FRNT against wild type (WT) and omicron BA.5 strains of SARS-CoV-2 in PLWH with CD4 T-cell count ≥ 500 cells/mm3(high CD4 recovery, HCDR) were comparable to HC, but they were significantly decreased in PLWH with CD4 T-cell count < 500/mm3 (low CD4 recovery, LCDR). After adjusting for age, gender, viral suppression, and number of preexisting comorbidities, CD4 T-cell counts < 500/mm3 significantly predicted a poor magnitude of neutralizing antibodies against WT, omicron BA.5, and XBB 1.5 strains among PLWH. Multivariable linear regression adjusting for age and gender revealed that LCDR was associated with reduced neutralizing activity (P = 0.017) and interferon-γ-producing T-cell responses (P = 0.049 for CD T-cell; P = 0.014 for CD8 T-cell) against WT, and strongly associated with more decreased cross-neutralization against omicron BA.5 strains (P < 0.001). Conclusion HCDR demonstrated robust humoral and cell-mediated immune responses after a booster dose of ancestral SARS-CoV-2 vaccine, whereas LCDR showed diminished immune responses against WT virus and more impaired cross-neutralization against omicron BA.5 strain.

Purpose: Breast cancer gene (BRCA) mutation is a well-known risk factor for breast cancer, and clinical interest in prophylactic mastectomy has increased in recent years.We investigated patients who were BRCA mutation carriers and underwent contralateral risk-reducing mastectomy (RRM), focusing on the incidence of occult malignancy after contralateral RRM. Methods: Prospectively collected data of patients with breast cancer treated at a single institution were retrospectively reviewed. Patients who underwent RRM with BRCA mutation who underwent RRM between January 2010 and November 2023 were included in this study.Among patients who underwent contralateral RRM, those with a primary cancer diagnosis were included, and those with occult malignancy on the contralateral RRM side were reviewed additionally. The demographics and pathologies of both primary breast cancer and occult malignancies were evaluated. Results: In our institution, 925 patients were identified as BRCA mutation carriers, and 320 patients underwent contralateral RRM along with primary breast cancer surgery. BRCA2 mutation occurred more frequently (54.8%) in the overall BRCA mutation cohort. Furthermore, we reviewed 320 patients diagnosed with breast cancer and detected as BRCA mutation carriers who underwent contralateral RRM; high proportion of them were BRCA1 mutation carriers.Interestingly, we found a low incidence of only seven patients (2.2%) with occult malignancy on contralateral RRM side, which is different from that reported in other nations. Conclusion The incidence of occult malignancy in the contralateral breast of breast cancer patients with breast cancer with BRCA mutation is significantly low, and may be influenced by several factors. Increased utilization of screening and advancements in diagnostic technologies in South Korea have reduced the chance of occult malignancy in RRM, and a variety of pathologic examination methods may affect the rate of incidence.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Purpose: Developmentally regulated GTP-binding protein 2 (DRG2) regulates microtubule dynamics and G2/M arrest during docetaxel treatment. Poly ADP-ribose polymerase (PARP) acts as an important repair system for DNA damage caused by docetaxel treatment. This study investigated whether DRG2 expression affects response to PARP inhibitors (olaparib) using prostate cancer cell lines PC3, DU145, LNCaP-FGC, and LNCaP-LN3. Materials and Methods: The cell viability and DRG2 expression levels were assessed using colorimetric-based cell viability assay and western blot. Cells were transfected with DRG2 siRNA, and pcDNA6/V5-DRG2 was used to overexpress DRG2. Flow cytometry was applied for cell cycle assay and apoptosis analysis using the Annexing V cell death assay. Results: The expression of DRG2 was highest in LNCaP-LN3 and lowest in DU145 cells. Expressions of p53 in PC3, DU145, and the two LNCaP cell lines were null-type, high-expression, and medium-expression, respectively. In PC3 (DRG2 high, p53 null) cells, docetaxel increased G2/M arrest without apoptosis; however, subsequent treatment with olaparib promoted apoptosis. In DU145 and LNCaP-FGC (DRG2 low), docetaxel increased sub-G1 but not G2/M arrest and induced apoptosis, whereas olaparib had no additional effect. In LNCaP-LN3 (DRG2 high, p53 wild-type), docetaxel increased sub-G1 and G2/M arrest, furthermore olaparib enhanced cell death. Docetaxel and olaparib combination treatment had a slight effect on DRG2 knockdown PC3, but increased apoptosis in DRG2-overexpressed DU145 cells. Conclusions DRG2 and p53 expressions play an important role in prostate cancer cell lines treated with docetaxel, and DRG2 levels can predict the response to PARP inhibitors.

Carpal tunnel syndrome (CTS) is a common form of hand mononeuropathy that is typi-cally caused by median nerve compression. Although it is often idiopathic, CTS can also result from various conditions, including space-occupying lesions. Tumoral calcinosis, a rare condition characterized by periarticular deposition of calcified masses, is an un-common cause of secondary CTS. We present a case of a 78-year-old woman with idio-pathic tumoral calcinosis that caused secondary CTS. Despite conservative treatments, her symptoms persisted, and diagnostic imaging, including radiographs, computed to-mography, and magnetic resonance imaging, revealed a calcified mass in the carpal tun-nel. A surgical intervention involving carpal tunnel release and excisional biopsy con-firmed the diagnosis of tumoral calcinosis. Postoperatively, the patient showed complete resolution of symptoms, with no recurrence on follow-up radiographs. This case high-lights the importance of considering space-occupying lesions, such as tumoral calcinosis, as a rare but treatable cause of secondary CTS.

BACKGROUND/OBJECTIVES: Isoflavones are estrogen-like compounds found in plants and their health effects remain equivocal. We investigated dietary isoflavone intake and its associated factors in Korean breast cancer survivors, with a comparison to cancer-free women. SUBJECTS/METHODS: The usual dietary intake of breast cancer survivors (n = 981, mean age 52 yrs) in 9 hospitals between 2012 and 2019 was assessed using 3-day food records or food frequency questionnaires (FFQs). They were age-matched to 2,943 cancer-free women who completed FFQs as part of a nationwide study conducted between 2012 and 2016. We used the flavonoid database of common Korean foods and the Phenol-Explorer database to estimate isoflavone intake. The contribution of each food or food group to the total isoflavone intake was calculated. The adjusted least-squares means of dietary isoflavone intake according to lifestyle and clinical factors were calculated using generalized linear models. RESULTS: Breast cancer survivors had a higher mean dietary isoflavone intake (23.59 mg/day) than cancer-free women (17.81 mg/day). Major food sources, including tofu, soybeans, and doenjang, contributed to over 70% of the isoflavone intake in both groups. When we estimated dietary isoflavone intake according to lifestyle characteristics, isoflavone intake increased with higher scores of adherence to the American Cancer Society dietary guidelines but decreased with increasing body mass index in both groups. Among cancer-free women, dietary isoflavone intake was higher among those who had never smoked and among dietary supplement users. Among breast cancer survivors, dietary isoflavone intakes did not vary with clinical characteristics, including time since surgery and estrogen receptor status. CONCLUSION Breast cancer survivors were more likely to consume isoflavones than agematched cancer-free women. Dietary isoflavone intake was associated with healthy lifestyle characteristics in women both with and without breast cancer. Further research is needed to understand the role of the higher isoflavone intake among breast cancer survivors compared to cancer-free women on their prognosis.

Background and Objectives: Evidence remains limited on the real-world prescription of very low-dose oral anticoagulation among frail patients with atrial fibrillation (AF). We described the practice patterns, effectiveness, and safety of very low-dose edoxaban (15 mg once daily). Methods: Patients with AF prescribed edoxaban 15 mg once daily in 2 tertiary hospitals between 2016 and September 2022 were included. Baseline clinical characteristics and clinical outcomes of interest were thromboembolic and bleeding events. Results: A total of 674 patients were included (mean age 78.3±9.1, 49.7% aged ≥80 years, 49.3% women, median follow-up 1.0±1.2 years). Mean CHA 2 DS 2 -VASc score was 3.9±1.6, and the modified HAS-BLED score was 2.0±1.1. Between 2016 and 2022, the number of very lowdose edoxaban prescriptions increased. The main reasons for the prescription of very lowdose were low body weight (55.5% below 60 kg), anaemia (62.8%), chronic kidney disease (40.2%), active cancer (15.3%), concomitant anti-platelet use (26.7%), and prior major bleeding (19.7%). During a median follow-up duration of 8 (interquartile range 3–16) months, overall thromboembolic and bleeding events occurred in 16 (2.3%) and 88 (13.1%) patients, respectively. Compared to the expected event rates on the established risk scoring systems, patients receiving very low-dose edoxaban demonstrated a 61% reduction in ischemic stroke, a 68% reduction of ischemic stroke/transient ischemic attack/systemic embolism, whereas a 49% increase in major bleeding. Conclusions The prescription of very low-dose edoxaban was increased over time, attributable to various clinical factors. The use of very low-dose edoxaban reduced the expected risk of thromboembolic events.