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.

Purpose: Human epidermal growth factor receptor 2 (HER2) is amplified or overexpressed in various malignancies, including breast and gastric cancers, and is associated with poor prognosis. Although HER2-targeted therapies, such as trastuzumab, improve outcomes in HER2-positive tumors, resistance often develops, and HER2-low tumors remain largely untargeted. Trastuzumab deruxtecan (T-DXd; DS-8201a) is a HER2-targeted antibody-drug conjugate with potent activity in HER2-positive and HER2-low tumors. This study evaluates its antitumor mechanisms and efficacy in HER2-positive, HER2-low, and homologous recombination deficiency (HRD)–associated models. Materials and Methods: Effects of T-DXd were assessed in cancer cell lines with diverse HER2 expression and HRD status. In vivo efficacy was evaluated using a xenograft model derived from HER2-low SNU-601 gastric cancer cells. Results: T-DXd reduced HER2 phosphorylation and downstream signaling (AKT, ERK) in HER2-positive cells. It induced DNA damage accumulation, as evidenced by increased γH2AX and p-Chk1 expression, and triggered apoptosis through cleaved poly(ADP-ribose) polymerase and caspase-3 activation, confirmed by annexin V staining. Similar effects were observed in HER2-low cells, with greater sensitivity in HRD cells. In xenografts, T-DXd reduced tumor volume by up to 80% at 4 mg/kg and 10 mg/kg. Histological analyses showed decreased Ki-67 and increased apoptosis. Furthermore, T-DXd induced G2/M cell cycle arrest and nuclear anaplasia, suggesting disruption of chromosomal stability as a potential antitumor mechanism. No significant toxicity, including body weight loss, was observed. Conclusion These findings highlight T-DXd’s effectiveness in HER2-low and HRD tumors, supporting its broader clinical application, including strategies targeting DNA damage repair pathways.

Purpose: Sustained cell proliferation and cell cycle acceleration in cancer cells inherently increase DNA damage, which interferes with homeostatic replication and transcription. Ataxia telangiectasia and Rad3-related (ATR) is crucial for initiation of the DNA damage response, and ATR inhibitors, such as elimusertib, induce increased replication stress and DNA damage. We investigated the anti-tumor effects of elimusertib and its mechanism of action in relation to replication stress. Materials and Methods: Anti-tumor effects were evaluated by MTT assay and colony formation assay in breast cancer cell lines in vitro, in breast cancer cell xenografts in vivo, and in patient-derived xenograft models. Cell cycle was assessed by flow cytometry and BrdU assay was used to measure replicating cells and S-phase progression. Alkaline and neutral comet assay was used to measure single and double-stranded DNA damages, respectively. Results: Elimusertib delayed S-phase progression in MDA-MB-453 and MDA-MB-231 cells and induced caspase-7–dependent apoptosis. Furthermore, the increase in sub-G1 population in the fluorescence-activated cell sorting analysis and Annexin V assay also confirmed apoptotic cell death. In the BrdU assay, single-stranded DNA (ssDNA) increased in sensitive cells and aberrant ssDNA induced DNA damage in S-phase and eventually caused replication catastrophe. Finally, these anti-tumor effects were proven in in vivo xenograft and patient-derived xenograft models. Conclusion Elimusertib had anti-tumor effects and induced replication catastrophe in breast cancer cells with a high replication rate. Moreover, cells under high DNA replication stress were sensitive to elimusertib. Further studies and treatment strategies with elimusertib are warranted for cancers with a high replication rate.

Limited data exist regarding the real-world practices and clinical outcomes in patients with ischemic heart failure with reduced left ventricular ejection fractions (LVEFs).Using nationwide registry data from South Korea, we aimed to investigate long-term outcomes and clinical practices, especially implantable cardioverter defibrillators (ICDs) implantation, in patients with reduced LVEFs at least 40 days after acute myocardial infarction (AMI). Of 13,056 patients with AMI between 2011 and 2015, we analyzed 350 (median age, 66 years [interquartile range, 56-75]) who had LVEFs <40% on follow-up transthoracic echocardiogram 40 days after the index event. The primary outcome was cardiac-cause mortality at 3 years. Secondary outcomes comprised major cardiovascular events as well as outcomes defined by the use of ICDs, cardiac resynchronization therapy defibrillators (CRT-Ds), and electrophysiology studies. Among 350 patients, 39 (11.1%) died from cardiac causes during 3 years of follow-up. Eleven (3.1%) were hospitalized for ventricular tachycardia. The rate of ICD or CRT-D implantation up to 3 years was 5.7% (20/350). Cox time-to-event analysis revealed older age, LVEF <30%, diabetes mellitus, and previous MI or revascularization as positively associated with cardiac death, whereas the use of statins and body weight <67 kg were negatively associated. This nationwide Korean registry demonstrated that only 5.7% of patients who had reduced LVEFs after 40 days of AMI underwent ICD implantations over 3 years. Considering the high mortality, concerted efforts are needed to improve clinical outcomes for patients who may have been candidates for ICD implantation.

Abrupt vessel closure (AVC) is a complication of percutaneous coronary intervention (PCI) and is defined as the sudden cessation of forward coronary blood flow due to a variety of mechanisms. The incidence of AVC has markedly decreased from approximately 3.0% in the early era to about 0.3% today. Nevertheless, cardiovascular interventionists must remain prepared to manage AVC effectively, given its significant impact on clinical outcomes.AVC can arise from several mechanisms, including dissection, intramural hematoma, intracoronary thrombosis, air embolism, vasospasm, and no-reflow. The clinical impact of AVC varies depending on the extent of myocardium affected, ranging from asymptomatic events or transient ischemic chest pain to cardiogenic shock or cardiac arrest. Both a general approach for stabilizing hemodynamic consequences and an etiology-specific management strategy are essential. Hasty decision-making may worsen the situation, whereas a structured approach—focused on hemodynamic stabilization, logical diagnostic processes, and targeted interventions—can improve outcomes. In this narrative review, we describe the mechanisms underlying each etiology, outline mechanism-specific management strategies, and discuss general approaches to managing patients with AVC through logical diagnostic and treatment processes. We hope this review offers valuable insights into this uncommon but significant complication and enhances readers’ skills in managing AVC more effectively during PCI.

Background: and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes. Methods: We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data. Results: Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4. Conclusion Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.

Background and Objectives: Cigarette smoking is a major risk factor for atherosclerosis.Nicotine, a crucial constituent of tobacco, contributes to atherosclerosis development and progression. However, evidence of the association between nicotine and neointima formation is limited. We aimed to evaluate whether nicotine enhances neointimal hyperplasia in the native epicardial coronary arteries of pigs after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Methods: After coronary angiography (CAG) and quantitative coronary angiography (QCA), we implanted 20 DES into 20 pigs allocated to 2 groups: no-nicotine (n=10) and nicotine (n=10) groups. Post-PCI CAG and QCA were performed immediately. Follow-up CAG, QCA, optical coherence tomography (OCT), and histopathological analyses were performed 2 months post-PCI. Results: Despite intergroup similarities in the baseline QCA findings, OCT analysis showed that the nicotine group had a smaller mean stent and lumen areas, a larger mean neointimal area, greater percent area stenosis, and higher peri-strut fibrin and inflammation scores than the no-nicotine group. In immunofluorescence analysis, the nicotine group displayed higher expression of CD68 and α-smooth muscle actin but lower CD31 expression than the no-nicotine group. Conclusions Nicotine inhibited re-endothelialization and promoted inflammation and NIH after PCI with DES in a porcine model.

Purpose: Since 1995, the Korean Gastric Cancer Association (KGCA) has been periodically conducting nationwide surveys on patients with surgically treated gastric cancer. This study details the results of the survey conducted in 2023. Materials and Methods: The survey was conducted from March to December 2024 using a standardized case report form. Data were collected on 86 items, including patient demographics, tumor characteristics, surgical procedures, and surgical outcomes. The results of the 2023 survey were compared with those of previous surveys. Results: Data from 12,751 cases were collected from 66 institutions. The mean patient age was 64.6 years, and the proportion of patients aged ≥71 years increased from 9.1% in 1995 to 31.7% in 2023. The proportion of upper-third tumors slightly decreased to 16.8% compared to 20.9% in 2019. Early gastric cancer accounted for 63.1% of cases in 2023.Regarding operative procedures, a totally laparoscopic approach was most frequently applied (63.2%) in 2023, while robotic gastrectomy steadily increased to 9.5% from 2.1% in 2014.The most common anastomotic method was the Billroth II procedure (48.8%) after distal gastrectomy and double-tract reconstruction (51.9%) after proximal gastrectomy in 2023.However, the proportion of esophago-gastrostomy with anti-reflux procedures increased to 30.9%. The rates of post-operative mortality and overall complications were 1.0% and 15.3%, respectively. Conclusions The results of the 2023 nationwide survey demonstrate the current status of gastric cancer treatment in Korea. This information will provide a basis for future gastric cancer research.

The Korean Society of Gynecologic Oncology has updated its clinical practice guidelines for endometrial cancer to incorporate advancements in recent high-quality randomized controlled trials. These guidelines address evolving treatment paradigms, and are tailored to the Korean medical context. Key updates include a strong recommendation for doxorubicin/trabectedin combination therapy in metastatic or recurrent unresectable leiomyosarcoma based on the significant survival benefits demonstrated in a randomized controlled trial. For advanced or recurrent endometrial cancer, immune checkpoint inhibitors combined with chemotherapy have received strong recommendations, owing to their proven efficacy and increased accessibility in Korea. Conditional recommendations were made for combination therapies involving durvalumab and olaparib, reflecting their potential benefits, but acknowledging regulatory and accessibility constraints. These guidelines aim to provide evidence-based, practical strategies to optimize care for patients with endometrial cancer while addressing unmet clinical needs and adapting global advancements to Korea’s healthcare environment.