Background: Current guidelines recommend factor IIa- or Xa-specific inhibitors over warfarin analogs for preventing thromboembolic stroke in patients with atrial fibrillation (AF).However, their plasma concentrations in Korean patients are not well understood. Methods: We conducted a single-center laboratory study to determine the distribution ranges of peak and trough concentrations of three factor Xa inhibitors (apixaban, edoxaban, and rivaroxaban) prescribed for preventing strokes in patients with AF. Patients receiving one of these drugs and undergoing blood specimen collection for laboratory tests were screened. Blood specimens were obtained from patients who had adhered to the prescribed drug regimen consistently for at least 1 week. Drug plasma concentrations were measured using heparin liquid-reagent technology-based anti-Xa chromogenic assays. Results: We selected 459 patients who were taking standard or on-label-reduced doses of apixaban (N = 252), edoxaban (N = 182), or rivaroxaban (N = 25). The 5th–95th percentile ranges of the peak concentrations were 84–414 ng/mL (apixaban), 72–424 ng/mL (edoxaban), and 97–517 ng/mL (rivaroxaban). The respective 5th–95th percentile ranges of the trough concentrations were 44–237 ng/mL, 23–93 ng/mL, and 13–219 ng/mL. Approximately 19.6% (apixaban), 33.3% (edoxaban), and 64.0% (rivaroxaban) of patients in each group had peak concentrations out of the predicted distribution ranges based on pharmacokinetic data. Approximately 7.3%, 52.8%, and 8.3% of patients had trough concentrations out of the predicted distribution ranges. Conclusions A considerable proportion of Korean patients with AF taking factor Xa inhibitors may require population-specific reference ranges to guide therapeutic monitoring.

Objective: To investigate whether breast tissue composition on preoperative automated breast ultrasound (ABUS) is associated with the accuracy of cancer multiplicity evaluation and postoperative recurrence-free survival (RFS) in patients with early-stage breast cancer. Materials and Methods: This retrospective analysis included women with early-stage breast cancer (clinical Tis, T1–2/N0) who underwent ABUS and digital mammography (DM) between October 2019 and April 2021. Tissue composition on ABUS was assessed using the Breast Imaging Reporting and Data System background echotexture (BE) (homogeneous-fat, homogeneous-fibroglandular, or heterogeneous). In a subgroup of patients with mammographically dense breasts, the glandular tissue component (GTC) on ABUS were further stratified into high (moderate or marked) or low (minimal or mild).Multivariable logistic and Cox regression analyses were used to identify factors associated with accurate cancer multiplicity categorization (unifocal, multifocal/multicentric, or bilateral) using ABUS + DM, and with RFS, respectively. Results: Among 409 women (mean age ± standard deviation, 50.2 ± 8.7 years), ABUS combined with DM yielded accurate cancer multiplicity categorization in 368 patients (90.0%). Neither BE nor GTC on ABUS affected the accuracy of categorization when ABUS was combined with DM. Over a median postoperative follow-up of 3.5 years, 11 recurrences occurred. Heterogeneous BE on ABUS (hazard ratio [HR] 11.24 [95% confidence interval [CI]: 2.82–44.92]; P = 0.001), BRCA mutation (HR 15.94 [2.47–102.97]; P = 0.004), and pathologic index cancer size (HR per 1-cm increase 1.91 [1.13–3.23];P = 0.02) was independently associated with RFS. In patients with dense breasts, heterogeneous BE (HR 14.17 [95% CI:2.69–74.60]; P = 0.002) and high GTC (HR 10.32 [2.35–45.28]; P = 0.002) on ABUS, BRCA mutation (HR 24.34 [2.75– 215.06]; P = 0.004), and pathologic cancer size (HR per 1-cm increase 2.62 [1.50–4.59]; P = 0.001) was independently associated with RFS. Conclusion In patients with early-stage breast cancer, heterogeneous BE and high GTC on preoperative ABUS, along with larger cancer size and BRCA mutation, was associated with worse RFS. However, BE and GTC did not affect cancer multiplicity evaluation when ABUS was used in combination with DM.

BACKGROUND/OBJECTIVES: Dietary supplement use is common among breast cancer survivors, but studies on Asian populations remain limited. This study investigated dietary supplement use among Korean breast cancer survivors, distinguishing between vitamin/ mineral (VM) and non-vitaminon-mineral (NVNM) supplements. SUBJECTS/METHODS: This cross-sectional study included 1,136 stage I–III breast cancer survivors from 12 Korean hospitals, who survived more than 6 mon post-surgery. The participants completed a questionnaire on post-diagnostic dietary supplement use. Stepwise logistic regression was applied, calculating odds ratios (ORs) and 95% confidence intervals (CIs) to identify the demographic and clinical factors associated with VM and NVNM use. RESULTS: Seventy percent of survivors reported supplement use, with 25% using a single product. The most common VM supplements were multivitamins/minerals, vitamin D, and vitamin C, while the most common NVNM supplements included omega-3 fatty acids, probiotics, and ginseng. Survivors with higher education and greater physical activity were more likely to use VM supplements (ORs [95% CIs], 2.74 [1.76–4.25] for college graduates or above vs. middle school or below; 1.38 [1.02–1.88] for the most active group vs. the least active group). NVNM use was associated with higher education, greater physical activity levels, and a history of smoking (ORs [95% CIs], 2.29 [1.46–3.58] for college graduates or above vs. middle school or below; 1.52 [1.13–2.06] for the most active group vs. the least active group; 2.00 [1.23–3.25] for ever smokers vs. never smokers). Survivors who had undergone chemotherapy were also more likely to use NVNM supplements than those who had not (OR [95% CI], 1.37 [1.02–1.84]). CONCLUSION Seventy percent of Korean breast cancer survivors used dietary supplements in this study. VM use was associated with higher education and physical activity, while higher NVNM use was associated with higher education, greater physical activity, a history of smoking, and chemotherapy.

Alzheimer’s disease (AD) is increasingly recognized as a disorder with significant vascular involvement, with microvascular damage and thromboinflammation often preceding classical amyloid pathology by several years. Elevated levels of prothrombin and thrombin, along with aberrant platelet activation, have been reported in individuals with AD. We hypothesized that platelet hyperactivity in AD results from an exaggerated response to thrombin in the presence of elevated amyloid beta 1-40 (Aβ₁₋₄₀), a peptide that accumulates during the early stages of AD. Platelet activation in response to Aβ₁₋₄₀ and thrombin was assessed using aggregation assays with an aggregometer, adhesion measurements by confocal microscopy, and spreading via both confocal microscopy and scanning electron microscopy. Reactive oxygen species (ROS) production and integrin α IIbβ 3 activation were quantified by flow cytometry. The roles of NADPH oxidase (NOX), ROS, and integrin signaling were examined using selective inhibitors. Aβ₁₋₄₀ significantly enhanced thrombin-induced platelet adhesion, aggregation, and spreading via NOX-derived ROS and integrin α IIbβ 3 activation. Aβ₁₋₄₀ also promoted platelet binding to fibrinogen and cerebrovascular endothelial cells, accompanied by distinct morphological changes. Inhibition of NOX or integrin α IIbβ 3 significantly reduced these effects. These findings identify a novel Aβ₁₋₄₀–NOX–ROS–integrin α IIbβ 3 axis that drives platelet hyperactivation and cerebrovascular interactions in AD.Targeting this pathway with antithrombotic or antioxidative strategies may offer therapeutic potential in mitigating AD-associated vascular pathology.

Purpose: This study aimed to differentiate well-differentiated liposarcoma (WDLPS) from lipoma using the magnetic resonance imaging (MRI) findings and improve the preoperative diagnostic accuracy between the two tumors. Although lipoma is a benign tumor that does not necessarily require surgical intervention, WDLPS exhibits local aggressiveness and typically necessitates surgical excision, making its differentiation clinically significant. Materials and Methods: Among 363 patients diagnosed with lipoma or WDLPS at the authors’ institution between January 2013 and April 2022, 45 patients with lipoma and 15 with WDLPS were selected using propensity score matching based on age and sex. The following six MRI features were analyzed: tumor size, shape, septal thickness, tumor depth, fat content ratio, and the presence of nodular non-fatty tissue components. The sensitivity and specificity of each feature were evaluated. Results: Among the MRI features, the fat content ratio (specificity 95%) and the presence of nodular non-fatty tissue components (specificity 98%) were useful for excluding WDLPS, but their sensitivities were relatively low (46% and 27%). The sensitivities of other features, such as tumor size, shape, septal thickness, and depth, ranged from 47% to 67%, suggesting that MRI alone has limitations in reliably distinguishing the two tumors. In addition, fat content ratios below 75% and the presence of nodular non-fatty tissue components were significantly more common in WDLPS than in lipoma. Conclusion The MRI findings can serve as a useful tool for excluding WDLPS when differentiating it from lipoma. Nevertheless, MRI alone has limitations in achieving a definitive diagnosis because of the low sensitivity of individual features. Therefore, additional approaches such as radiomics analysis, artificial intelligence algorithms, and multicenter studies, are needed to improve the diagnostic accuracy and establish personalized treatment strategies.

Background: Vascular smooth muscle cells (VSMCs) play a crucial role in the development of occlusive vascular diseases through abnormal proliferation and migration. This pathological behavior is closely associated with mitochondrial reactive oxygen species (ROS)-mediated mitochondrial DNA (mtDNA) damage. The mitochondrial carrier protein solute carrier family 25 member 33 (SLC25A33), essential for nucleoside transport, is integral to mtDNA production. This study aimed to investigate the effects of SLC25A33 inhibition on the proliferation and migration of VSMCs, as well as its impact on neointima formation. Methods: VSMCs were isolated from the thoracic aorta of 4-week-old Sprague-Dawley rats. The effects of small interfering RNAinduced silencing of SLC25A33 mRNA on platelet-derived growth factor (PDGF)-induced proliferation and migration of VSMCs were analyzed. The in vivo effects of targeting the SLC25A33 gene on neointima formation were evaluated using a murine carotid artery ligation model by perivascularly applying Lenti-shSLC25A33 with Pluronic F-127 gel. Results: First, we observed an upregulation of the SLC25A33 protein in the carotid artery ligation-induced neointima in mice. Silencing of SLC25A33 suppressed the PDGF-stimulated proliferation and migration of VSMCs and cell cycle progression. Knockdown of SLC25A33 inhibited PDGF-induced production of mtDNA and ROS, consequently inactivating the cyclic GMP-AMP synthesis (cGAS)-stimulator of interferon genes (STING)-TANK-binding kinase 1 (TBK1)-nuclear factor kappa B (NF-κB) pathway. Furthermore, the downregulation of SLC25A33 reduced carotid artery ligation-induced neointima in mice. Conclusion This study suggests that targeting SLC25A33 in VSMCs could be a novel therapeutic strategy to prevent occlusive vascular diseases.

Neurodegenerative diseases (NDDs), characterized by the progressive deterioration of the structure and function of the nervous system, represent a significant global health challenge. Emerging research suggests that the gut microbiota plays a critical role in regulating neurodegeneration via modulation of the gut-brain axis. Probiotics, defined as live microorganisms that confer health benefits to the host, have garnered significant attention owing to their therapeutic potential in NDDs. This review examines the current research trends related to the microbiome-gut-brain axis across various NDDs, highlighting key findings and their implications. Additionally, the effects of specific probiotic strains, including Lactobacillus plantarum, Bifidobacterium breve, and Lactobacillus rhamnosus, on neurodegenerative processes were assessed, focusing on their potential therapeutic benefits. Overall, this review emphasizes the potential of probiotics as promising therapeutic agents for NDDs, underscoring the importance of further investigation into this emerging field.

This study aimed to investigate changes in candidemia incidence, species distribution, antifungal susceptibility, initial antifungal use, and mortality trends in Korea before and during the COVID-19 pandemic. A retrospective analysis was conducted on candidemia cases from two tertiary care hospitals in Korea between 2017 and 2022. Data were compared between the pre-pandemic (2017-2019) and pandemic (2020-2022) periods. Statistical methods included incidence rate ratios (IRRs) and multivariate Cox regression to assess 30-day mortality risk factors. A total of 470 candidemia cases were identified, with 48.7% occurring pre-pandemic and 51.3% during the pandemic. While the overall incidence of candidemia remained similar across the two periods (IRR 1.15;p=0.13), the incidence in intensive care units (ICUs) significantly increased during the pandemic (IRR 1.50; p<0.01). The distribution of Candida species did not differ significantly between the two periods. Fluconazole non-susceptibility in C. albicans markedly decreased (10.0% vs. 0.9%, p<0.01), whereas C. glabrata exhibited a significant rise in caspofungin non-susceptibility during the pandemic (0% vs. 22.4%, p<0.01).Echinocandin use increased (21.8% vs. 34.4%; p<0.01), while fluconazole use declined (48.0% vs. 32.8%; p<0.01). Although the 30-day mortality rate was higher during the pandemic (60.2% vs. 57.2%), the difference was not statistically significant (p=0.57).The findings highlight the need for region-specific surveillance and tailored management strategies to improve candidemia outcomes, especially during healthcare disruptions like the COVID-19 pandemic.

Objective: To evaluate the clinical efficacy of ultrafast dynamic contrast-enhanced (DCE)-MRI using a compressed sensing (CS) technique for differentiating benign and malignant soft-tissue tumors (STTs) and to evaluate the factors related to the grading of malignant STTs. Materials and Methods: A total of 165 patients (96 male; mean age, 61 years), comprising 111 with malignant STTs and 54 with benign STTs according to the 2020 WHO classification, underwent DCE-MRI with CS between June 2018 and June 2023. The clinical, qualitative, and quantitative parameters associated with conventional MRI were also obtained. During post-processing of the early arterial phase of DCE-MRI, the time-to-enhance (TTE), time-to-peak (TTP), initial area under the curve at 60 s (iAUC60), and maximum slope were calculated. Furthermore, the delayed arterial phase parameters of DCEMRI, including Ktrans , Kep, Ve, and iAUC values and time-concentration curve (TCC) types, were determined. Clinical and MRI parameters were statistically analyzed to differentiate between benign and malignant tumors and their correlation with tumor grading. Results: According to logistic regression analysis, the TTE value (P < 0.001) of the early arterial phase and Ve (P = 0.039) and iAUC (P = 0.006) values of the delayed arterial phase, as well as age, location, peritumoral edema, and contrast heterogeneity on conventional MRI, were significant (P = 0.001–0.015) in differentiating benign and malignant tumors. Among all the quantitative parameters, the TTE value had the highest accuracy, with an area under the receiver operating characteristic curve of 0.902. The grading of malignant tumors was significantly correlated with peritumoral edema; CE heterogeneity; visual diffusion restriction; minimum and mean ADC; TTP, Kep, and Ve values; and the TCC graph (all P < 0.05). Conclusion Among the quantitative parameters obtained using ultrafast DCE-MRI, early arterial phase TTE was the most accurate for distinguishing between benign and malignant tumors.