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 6-year post-marketing surveillance (PMS) study was conducted in South Korea to evaluate the real-world safety and effectiveness of eribulin in patients with advanced or metastatic breast cancer previously treated with anthracyclines and taxanes. Materials and Methods: During the study period (17 August 2012 to 16 August 2018), case-report files (CRFs) of patients receiving eribulin were collected. The main study endpoint was to assess the safety of eribulin. Evaluation of the effectiveness of eribulin was an exploratory endpoint. Patients were followed for 1 year after eribulin initiation. Results: CRFs were collected from 64 investigators at 64 sites for 1,079 patients. The safety analysis set (SAS) included 1,001 eribulin recipients; effectiveness was assessed in 244 patients. In the SAS, patients were predominantly female (99.6%), with a median age of 53.0 years, and diagnosed with metastatic breast cancer (92.0%). Eribulin was administered as a median 4th line chemotherapy. A total of 2,124 treatment-emergent adverse events (TEAEs) were reported in 661 patients (66.0%). Neutropenia was the most common TEAE (32.5% of patients), occurring at a median of 9-11 days from initial eribulin administration. Overall response and disease control rates were 31.7% and 95.6%, respectively, and the median duration of eribulin use (time to treatment failure) was 3.0 months. Conclusion This large real-world PMS analysis in patients with advanced or metastatic breast cancer demonstrated the effectiveness of eribulin and found no new safety concerns relative to safety information from prior clinical and real-world studies, and approvals in South Korea and other countries.

Secondary rhabdoid tumors (RTs) with atypical teratoid/rhabdoid tumor-like features rarely arise from, or coexist with, pleomorphic xanthoastrocytomas (PXAs), and their clinicopathological and molecular characteristics remain poorly understood. We report a 17-year-old girl with a temporal lobe mass that, upon gross total resection, pathologically contained both RT and PXA components. Immunohistochemistry revealed loss of INI1 expression restricted to the RT component, while the PXA area retained INI1. Next-generation sequencing identified a shared BRAF::TRIM24 fusion and homozygous deletion of CDKN2A/2B in both components, indicating a shared clonal origin. Additionally, a germline ATM frameshift mutation (c.5288_5289insGA) was identified in both tumor components, making the first such report in central nervous system tumors. SMARCB1 loss was confined to the RT component, further supporting the hypotheses of clonal evolution and secondary transformation. Despite gross total resection, craniospinal irradiation, and chemotherapy, the patient developed rapid leptomeningeal dissemination and died 5 months after surgery. This case provides clinicopathological and molecular evidence for clonal evolution and secondary transformation of PXA into an RT. The presence of germline ATM mutation may have therapeutic and biological relevance. Further studies are required to clarify the pathogenesis and optimal management of these rare and aggressive tumors.

Background: Arthroscopic repair of bucket-handle meniscal tears (BHMTs) is technically challenging owing to the complexity of the tear patterns. Compared to simpler meniscal tears, BHMTs are associated with a higher failure rate and often require subsequent meniscectomy. This study aimed to assess clinical outcomes, failure rates, and risk factors for failure following primary arthroscopic repair of BHMTs. Methods: Seventy-four patients (mean age, 27.2 ± 11.2 years) who underwent arthroscopic BHMT repair were included (mean follow-up period, 60.2 ± 36.0 months). Analyzed risk factors included age, sex, body mass index, chronicity, laterality, tear zone, and concomitant anterior cruciate ligament reconstruction. Clinical failure was defined as the presence of clinical symptoms consistent with a meniscus tear and the need for subsequent surgery. The Kaplan-Meier method and log-rank test were performed to compare groups classified by postoperative meniscal healing status on magnetic resonance imaging (MRI) at a mean follow-up period of 7.30 ± 1.80 months. Clinical outcomes were assessed using the Tegner activity score, Lysholm knee score, and Hospital for Special Surgery (HSS) knee score. Results: The clinical failure rate was 14.9% (11 / 74). Six patients underwent subtotal meniscectomy, and 5 patients underwent partial meniscectomy. Red-white zone involvement was a significant risk factor for clinical failure (odds ratio, 6.182; 95% CI, 1.093–34.950; p = 0.039). Survival analysis based on postoperative MRI findings revealed a significant difference among 3 groups (p = 0.008): the completely healed group showed a 100% survival rate (20 / 20); the partially healed group, 80% (32 / 40); and the unhealed group, 0% (0 / 5). Patients with lateral BHMTs had a significantly higher rate of complete healing than those with medial BHMTs (46.4% vs. 18.9%; p = 0.014). At the final follow-up, the non-failure group demonstrated significantly higher Tegner activity (5.1 ± 1.2 vs. 4.4 ± 0.5; p = 0.038), Lysholm knee (87.7 ± 6.2 vs. 83.2 ± 3.1; p = 0.029), and HSS knee (93.9 ± 4.7 vs. 89.6 ± 3.0; p = 0.007) scores than the failure group. Conclusions BHMTs involving the red-white zone or located in the medial meniscus—particularly those showing inferior early postoperative MRI healing—should be closely monitored after surgery.

Background/Aims: Patients with concurrent type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD) face elevated cardiovascular risks. However, optimal oral antidiabetic drug (OAD) selection for this population remains unclear. Methods: Using the Korean National Health Information Database, we conducted a target trial emulation comparing cardiovascular outcomes among patients with T2DM and MASLD (defined by fatty liver index ≥30) who initiated sodium-glucose cotransporter 2 (SGLT2) inhibitors, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors, or sulfonylureas with metformin. The primary outcome was major adverse cardiovascular events (MACE), including cardiovascular mortality, nonfatal myocardial infarction, and nonfatal stroke. Results: Among 71,071 patients (331,726 person-years), SGLT2 inhibitor users experienced a significantly lower MACE risk compared to sulfonylurea users (adjusted subdistribution hazard ratio [aSHR], 0.44; 95% confidence interval [CI], 0.31–0.62). SGLT2 inhibitors also demonstrated a lower MACE risk compared to thiazolidinediones (aSHR, 0.61; 95% CI, 0.39–0.96) and DPP-4 inhibitors (aSHR, 0.59; 95% CI, 0.42–0.96). Cardiovascular mortality risk was notably reduced with SGLT2 inhibitors compared to sulfonylureas (aSHR, 0.13; 95% CI, 0.03–0.50), thiazolidinediones (aSHR, 0.19; 95% CI, 0.04–0.86), and DPP-4 inhibitors (aSHR, 0.22; 95% CI, 0.06–0.84). Mediation analysis revealed that MASLD regression accounted for 8.7% of the total cardiovascular benefit when comparing SGLT2 inhibitors to sulfonylureas. Conclusions In patients with concurrent T2DM and MASLD, SGLT2 inhibitors demonstrated better cardiovascular outcomes compared to other OADs. These findings suggest that SGLT2 inhibitors may be the preferred OAD choice for cardiovascular risk reduction in this high-risk population.

The sixth edition of the Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) was published in 2025. This review compared KMAP-DD 2025 with four major international clinical practice guidelines: Canadian Network for Mood and Anxiety Treatments Clinical Guidelines for the Management of Major Depressive Disorders, National Institute for Health and Care Excellence Depression Guideline, Royal Australian and New Zealand College of Psychiatrists Clinical Practice Guidelines for Mood Disorders, and British Association for Psychopharmacology Guideline. While KMAP-DD is based on expert consensus, and others on evidence-based methods, overall treatment strategies for depressive episodes were fairly consistent. Especially, KMAP-DD 2025 offers more structured recommendations in areas lacking strong evidence, such as premenstrual dysphoric disorder, perinatal depression, and depression with medical comorbidities. KMAP-DD 2025 also reflected Korean clinical practice patterns emphasizing rapid symptom relief and early use of combination strategies. Despite limitations as a consensus-based guideline, KMAP-DD 2025 complements evidence-based approaches and provides practical, situation-specific guidance for real-world clinical decision-making in Korea.

In patients with differentiated thyroid cancer (DTC), initial recurrence risk stratification based on clinical, histopathological, and perioperative data remains the key determinant for guiding management strategies during the first 1-2 years post-treatment. However, the adoption of ongoing risk stratification (ORS), which dynamically reassesses risk by integrating longitudinal clinical data and treatment response, enables more precise long-term prognostic assessment and facilitates highly individualized management. Building upon recent guidelines, the 2026 KTA guideline has been further refined by incorporating robust evidence from large-scale national cohorts and comprehensive systematic reviews. These updated recommendations outline contemporary concepts of ORS, risk-adapted TSH suppression targets, optimized surveillance modalities for recurrence detection, and disease-specific long-term follow-up strategies. Reflecting the paradigm shift toward de-escalated treatment, this revision integrates evolved perspectives on TSH suppression intensity, the clinical interpretation of thyroglobulin levels, and tailored follow-up intervals. These evidence-based recommendations aim to minimize unnecessary treatment and excessive surveillance in the large proportion of patients with excellent prognosis after initial therapy, while ensuring that each patient receives appropriately tailored and effective long-term management.

Objective: To test the performance of an artificial intelligence-based computer-aided diagnosis (AI-CAD) designed for fullfield digital mammography (FFDM) when applied to synthetic mammography (SM). Materials and Methods: We analyzed 501 women (mean age, 57 ± 11 years) who underwent preoperative mammography and breast cancer surgery. This cohort consisted of 1002 breasts, comprising 517 with cancer and 485 without. All patients underwent digital breast tomosynthesis (DBT) and FFDM during the preoperative workup. The SM is routinely reconstructed using DBT. Commercial AI-CAD (Lunit Insight MMG, version 1.1.7.2) was retrospectively applied to SM and FFDM to calculate the abnormality scores for each breast. The median abnormality scores were compared for the 517 breasts with cancer using the Wilcoxon signed-rank test. Calibration curves of abnormality scores were evaluated. The discrimination performance was analyzed using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity using a 10% preset threshold. Sensitivity and specificity were further analyzed according to the mammographic and pathological characteristics.The results of SM and FFDM were compared. Results: AI-CAD demonstrated a significantly lower median abnormality score (71% vs. 96%, P < 0.001) and poorer calibration performance for SM than for FFDM. SM exhibited lower sensitivity (76.2% vs. 82.8%, P < 0.001), higher specificity (95.5% vs.91.8%, P < 0.001), and comparable AUC (0.86 vs. 0.87, P = 0.127) than FFDM. SM showed lower sensitivity than FFDM in asymptomatic breasts, dense breasts, ductal carcinoma in situ, T1, N0, and hormone receptor-positive/human epidermal growth factor receptor 2-negative cancers but showed higher specificity in non-cancerous dense breasts. Conclusion AI-CAD showed lower abnormality scores and reduced calibration performance for SM than for FFDM.Furthermore, the 10% preset threshold resulted in different discrimination performances for the SM. Given these limitations, off-label application of the current AI-CAD to SM should be avoided.

BACKGROUND/OBJECTIVES: Green Citrus junos (yuja) peel extract has higher naringin and hesperidin contents and antioxidant activity than yellow yuja peel extract, but its anti-obesity effects are unclear. This study examined the anti-obesity properties of green yuja peel ethanol extract (GYE) in 3T3-L1 cells and high-fat diet (HFD)-induced obese mice.MATERIALS/METHODS: The effects of GYE on adipocyte differentiation were assessed by measuring Oil red O staining, mRNA and protein expression. The beneficial effects of GYE on HFD-induced obese mice were evaluated using the body weight, body composition, visceral fat size, and biochemical analysis. RESULTS: GYE inhibited adipocyte differentiation and lipid accumulation compared to the control cells, as evidenced by Oil red O staining and the triglyceride level, respectively.GYE down-regulated the adipogenic genes CCAAT/enhancer binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ), and lipogenic gene diacylglycerol O-acyltransferase 2 (DGAT2). GYE at 100 μg/mL downregulated the phosphorylation levels of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt), and their downstream targets PPARγ and sterol regulatory element-binding protein-1 (SREBP-1c) compared to the control group. In obese mice, GYE (100 mg/kg/day) reduced the body weight, body weight gain, and serum lipid level compared to the control group. Analysis using dual-energy X-ray absorptiometry showed that GYE decreased the fat percentage, fat in tissue, and abdominal circumference, while it increased the lean percentage compared to control group.Furthermore, GYE significantly reduced the visceral fat weight and size compared to the control group. CONCLUSION GYE suppressed adipocyte differentiation by inhibiting the PI3K-Akt pathway in vitro and reduced the body fat mass and visceral adiposity in HFD-induced obese mice.These findings suggest that GYE is a viable natural option for combating obesity.

Background: Small cell lung cancer (SCLC) is called ‘smoker’s disease’ because it is strongly associated with smoking and most cases occur in smokers. However, it can also occur in never smokers. We investigated the clinical features of never smokers with SCLC and compared their treatment outcomes with those of smokers with SCLC. Methods: We retrospectively reviewed the clinical data of patients who had proven SCLC and had received chemotherapy at a single cancer center between July 2002 and April 2021. Results: Of 1,643 patients, 1,416 (86.2%) were enrolled in this study. A total of 162 (11.4%) and 1,254 (88.6%) patients were never smokers and smokers, respectively. There were more female never smokers than smokers (n=130; 80.2% vs. 79, 6.3%, p=0.000), and the incidence of ischemic heart disease was lower among never smokers than among smokers (4/1,416, [2.5%] vs. 83/1,416 [6.6%], p=0.036). Never smokers showed less symptoms at diagnosis than smokers (80.9% vs. 87.2%, p=0.037); however, they showed more toxicity after first-line treatment (61.7% vs. 47.8%, p=0.001). The objective response rate (ORR) was significantly higher in never smokers (74.1% vs. 59.6%, p=0.000). In the multivariate analysis, never smoking and second-line treatment were associated with a better ORR. However, progression-free survival and overall survival were not significantly different between never smokers and smokers. Conclusion In conclusion, never smokers accounted for 11.4% of patients with SCLC. They had distinguishing clinical characteristics and showed better chemotherapeutic responses than smokers.