Subarachnoid hemorrhage (SAH) is a stroke subtype with high mortality and poor functional outcomes. Prompt occlusion of a ruptured aneurysm at an early stage is crucial to prevent rebleeding, which can result in even higher mortality and more severe disabilities. The most critical initial decision in SAH management is the choice of treatment method with surgical clipping or endovascular coiling. We aimed to develop an evidence-based clinical guideline to select the optimal initial treatment in patients with SAH. We developed this guideline based on evidence from systematic reviews and meta-analyses via a de novo process. A systematic literature review was conducted across four databases (MEDLINE, Embase, Cochrane, and KoreaMed) to answer two population, intervention, comparison, outcome questions comparing clipping and coiling. The risk of bias was assessed using ROB 2.0 and the Newcastle-Ottawa Scale. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagrams and meta-analyses were generated for functional outcome and mortality. We included six randomized control trials (RCTs) and 58 observational studies. Meta-analysis of RCTs showed that coiling improved functional outcomes compared to clipping (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.86–0.97). No significant mortality difference was observed in RCTs (OR, 1.38; 95% CI, 0.91–2.09), but non-RCTs favored clipping for reduced mortality (OR, 0.77; 95% CI, 0.69–0.86). However, it is difficult to generalize these findings to all clinical situations, as patients with SAH have a highly variable clinical course. Final treatment decision should be tailored to the individual patient’s status, including aneurysm location, morphology, and the expertise available at the treatment center. Such decisions are best made by specialists such as a board-certified physician and should be explained to the patient and their caregivers, along with the rationale for selecting the most appropriate treatment at the given hospital. Korea has many certified endovascular neurosurgeons, cerebrovascular surgeons, and certified cerebrovascular centers. Proper selection of the most suitable treatment method by certified physicians and centers would greatly benefit patient outcomes and healthcare professionals.

The mothership (MS) model, where patients are directly transferred to a thrombectomy-capable center, and the drip-and-ship (DS) model, where thrombolysis is initiated at the nearest primary stroke center before transfer for thrombectomy, are the primary transport modes for patients with stroke. We aimed to establish guidelines for selecting the appropriate transfer strategy based on emergent large vessel occlusion (LVO). We developed this guideline based on evidence from systematic reviews and meta-analyses via a de novo process. A systematic literature review was conducted across four databases (MEDLINE, Embase, Cochrane, and KoreaMed) to answer three Population, Intervention, Comparison, and Outcome questions comparing MS and DS models. The risk of bias was assessed using the Newcastle-Ottawa Scale. Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagrams and meta-analyses were generated for functional outcomes, mortality, and successful recanalization. Twenty-six non-randomized controlled studies showed that the MS model improved good functional outcomes by approximately 14% compared with the DS model (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.00–1.30). Fifteen studies reported that mortality in the MS and DS models showed no significant differences (OR, 0.97; 95% CI, 0.84–1.11). Twenty-four studies revealed no significant difference in successful recanalization between the MS and DS models (OR, 0.87; 95% CI, 0.68–1.10). The MS model should be considered first to improve the functional outcome of patients with LVO. However, if thrombectomy cannot be performed immediately after thrombolysis, or if a thrombectomy-enabled hospital is not nearby, the DS model should be considered by stroke specialists depending on transportation time and regional factors. We suggest a mixed approach with the DS model based on specific circumstances or regions to ensure the optimum treatment of patients with acute ischemic stroke (AIS). Appropriate transport for patients with LVO improves the prognosis of AIS.

OBJECTIVES: The escalating burden of cardiovascular disease (CVD) is a critical public health issue worldwide. CVD, especially acute myocardial infarction (AMI) and stroke, is the leading contributor to morbidity and mortality in Korea. We aimed to develop algorithms for identifying AMI and stroke events from the National Health Insurance Service (NHIS) database and validate these algorithms through medical record review. METHODS: We first established a concept and definition of “hospitalization episode,” taking into account the unique features of health claims-based NHIS database. We then developed first and recurrent event identification algorithms, separately for AMI and stroke, to determine whether each hospitalization episode represents a true incident case of AMI or stroke. Finally, we assessed our algorithms’ accuracy by calculating their positive predictive values (PPVs) based on medical records of algorithm- identified events. RESULTS: We developed identification algorithms for both AMI and stroke. To validate them, we conducted retrospective review of medical records for 3,140 algorithm-identified events (1,399 AMI and 1,741 stroke events) across 24 hospitals throughout Korea. The overall PPVs for the first and recurrent AMI events were around 92% and 78%, respectively, while those for the first and recurrent stroke events were around 88% and 81%, respectively. CONCLUSIONS We successfully developed algorithms for identifying AMI and stroke events. The algorithms demonstrated high accuracy, with PPVs of approximately 90% for first events and 80% for recurrent events. These findings indicate that our algorithms hold promise as an instrumental tool for the consistent and reliable production of national CVD statistics in Korea.

Background: and Purpose In young patients (aged 18–60 years) with patent foramen ovale (PFO)- associated stroke, percutaneous closure has been found to be useful for preventing recurrent ischemic stroke or transient ischemic attack (TIA). However, it remains unknown whether PFO closure is also beneficial in older patients. Methods: Patients aged ≥60 years who had a cryptogenic stroke and PFO from ten hospitals in South Korea were included. The effect of PFO closure plus medical therapy over medical therapy alone was assessed by a propensity-score matching method in the overall cohort and in those with a high-risk PFO, characterized by the presence of an atrial septal aneurysm or a large shunt. Results: Out of the 437 patients (mean age, 68.1), 303 (69%) had a high-risk PFO and 161 (37%) patients underwent PFO closure. Over a median follow-up of 3.9 years, recurrent ischemic stroke or TIA developed in 64 (14.6%) patients. In the propensity score-matched cohort of the overall patients (130 pairs), PFO closure was associated with a significantly lower risk of a composite of ischemic stroke or TIA (hazard ratio [HR]: 0.45; 95% confidence interval [CI]: 0.24–0.84; P=0.012), but not for ischemic stroke. In a subgroup analysis of confined to the high-risk PFO patients (116 pairs), PFO closure was associated with significantly lower risks of both the composite of ischemic stroke or TIA (HR: 0.40; 95% CI: 0.21–0.77; P=0.006) and ischemic stroke (HR: 0.47; 95% CI: 0.23–0.95; P=0.035). Conclusion Elderly patients with cryptogenic stroke and PFO have a high recurrence rate of ischemic stroke or TIA, which may be significantly reduced by device closure.

Background and Objectives: Concerns remain that early aspirin cessation may be associated with potential harm in subsets at high risk of ischemic events. This study aimed to assess the effects of P2Y12 inhibitor monotherapy after 3-month dual antiplatelet therapy (DAPT) vs.prolonged DAPT (12-month or longer) based on the ischemic risk stratification, the CHADSP2A2RC, after percutaneous coronary intervention (PCI). Methods: This was a sub-study of the SMART-CHOICE trial. The effect of the randomized antiplatelet strategies was assessed across 3 CHADS-P2A2RC risk score categories. The primary outcome was a major adverse cardiac and cerebral event (MACCE), a composite of all-cause death, myocardial infarction, or stroke. Results: Up to 3 years, the high CHADS-P2A2RC risk score group had the highest incidence of MACCE (105 [12.1%], adjusted hazard ratio [HR], 2.927; 95% confidence interval [CI], 1.358–6.309; p=0.006) followed by moderate-risk (40 [1.4%], adjusted HR, 1.786; 95% CI, 0.868–3.674; p=0.115) and low-risk (9 [0.5%], reference). In secondary analyses, P2Y12 inhibitor monotherapy reduced the Bleeding Academic Research Consortium (BARC) types 2, 3, or 5 bleeding without increasing the risk of MACCE as compared with prolonged DAPT across the 3 CHADS-P2A2RC risk strata without significant interaction term (interaction p for MACCE=0.705 and interaction p for BARC types 2, 3, or 5 bleeding=0.055). Conclusions The CHADS-P2A2RC risk score is valuable in discriminating high-ischemicrisk patients. Even in such patients with a high risk of ischemic events, P2Y12 inhibitor monotherapy was associated with a lower incidence of bleeding without increased risk of ischemic events compared with prolonged DAPT.

Background: The risk of device thrombosis and device-oriented clinical outcomes with bioresorbable vascular scaffold (BVS) was reported to be significantly higher than with contemporary drug-eluting stents (DESs). However, optimal device implantation may improve clinical outcomes in patients receiving BVS. The current study evaluated mid-term safety and efficacy of Absorb BVS with meticulous device optimization under intravascular imaging guidance. Methods: The SMART-REWARD and PERSPECTIVE-PCI registries in Korea prospectively enrolled 390 patients with BVS and 675 patients with DES, respectively. The primary endpoint was target vessel failure (TVF) at 2 years and the secondary major endpoint was patientoriented composite outcome (POCO) at 2 years. Results: Patient-level pooled analysis evaluated 1,003 patients (377 patients with BVS and 626 patients with DES). Mean scaffold diameter per lesion was 3.24 ± 0.30 mm in BVS group.Most BVSs were implanted with pre-dilatation (90.9%), intravascular imaging guidance (74.9%), and post-dilatation (73.1%) at proximal to mid segment (81.9%) in target vessel.Patients treated with BVS showed comparable risks of 2-year TVF (2.9% vs. 3.7%, adjusted hazard ratio [HR], 1.283, 95% confidence interval [CI], 0.487–3.378, P = 0.615) and 2-year POCO (4.5% vs. 5.9%, adjusted HR, 1.413, 95% CI, 0.663–3.012,P = 0.370) than those with DES. The rate of 2-year definite or probable device thrombosis (0.3% vs. 0.5%, P = 0.424) was also similar. The sensitivity analyses consistently showed comparable risk of TVF and POCO between the 2 groups. Conclusion With meticulous device optimization under imaging guidance and avoidance of implantation in small vessels, BVS showed comparable risks of 2-year TVF and device thrombosis with DES.

Objective: The International Cooperative Ataxia Rating Scale (ICARS) is a semiquantitative clinical scale for ataxia that is widely used in numerous countries. The purpose of this study was to investigate the validity and reliability of the Korean-translated version of the ICARS. Methods: Eighty-eight patients who presented with cerebellar ataxia were enrolled. We investigated the construct validity using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). We also investigated the internal consistency using Cronbach’s α and intrarater and interrater reliability using intraclass correlation coefficients. Results: The Korean-translated ICARS showed satisfactory construct validity using EFA and CFA. It also revealed good interrater and intrarater reliability and showed acceptable internal consistency. However, subscale 4 for assessing oculomotor disorder showed moderate internal consistency. Conclusion This is the first report to investigate the validity and reliability of the Korean-translated ICARS. Our results showed excellent construct and convergent validity. The reliability is also acceptable.

The development of drug-resistant influenza and new pathogenic virus strains underscores the need for antiviral therapeutics. Currently, neuraminidase (NA) inhibitors are commonly used antiviral drugs approved by the US Food and Drug Administration (FDA) for the prevention and treatment of influenza. Here, we show that vitisin B (VB) inhibits NA activity and suppresses H1N1 viral replication in MDCK and A549 cells. Reactive oxygen species (ROS), which frequently occur during viral infection, increase virus replication by activating the NF-κB signaling pathway, downmodulating glucose-6-phosphate dehydrogenase (G6PD) expression, and decreasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response activity. VB decreased virus-induced ROS generation by increasing G6PD expression and Nrf2 activity, and inhibiting NF-κB translocation to the nucleus through IKK dephosphorylation. In addition, VB reduced body weight loss, increased survival, decreased viral replication and the inflammatory response in the lungs of influenza A virus (IAV)-infected mice. Taken together, our results indicate that VB is a promising therapeutic candidate against IAV infection, complements existing drug limitations targeting viral NA. It modulated the intracellular ROS by G6PD, Nrf2 antioxidant response pathway, and NF-κB signaling pathway. These results demonstrate the feasibility of a multi-targeting drug strategy, providing new approaches for drug discovery against IAV infection.

Background: Fractional flow reserve (FFR) based on computed tomography (CT) has been shown to better identify ischemia-causing coronary stenosis. However, this current technology requires high computational power, which inhibits its widespread implementation in clinical practice. This prospective, multicenter study aimed at validating the diagnostic performance of a novel simple CT based fractional flow reserve (CT-FFR) calculation method in patients with coronary artery disease. Methods: Patients who underwent coronary CT angiography (CCTA) within 90 days and invasive coronary angiography (ICA) were prospectively enrolled. A hemodynamically significant lesion was defined as an FFR ≤ 0.80, and the area under the receiver operating characteristic curve (AUC) was the primary measure. After the planned analysis for the initial algorithm A, we performed another set of exploratory analyses for an improved algorithm B. Results: Of 184 patients who agreed to participate in the study, 151 were finally analyzed.Hemodynamically significant lesions were observed in 79 patients (52.3%). The AUC was 0.71 (95% confidence interval [CI], 0.63–0.80) for CCTA, 0.65 (95% CI, 0.56–0.74) for CT-FFR algorithm A (P = 0.866), and 0.78 (95% CI, 0.70–0.86) for algorithm B (P = 0.112). Diagnostic accuracy was 0.63 (0.55–0.71) for CCTA alone, 0.66 (0.58–0.74) for algorithm A, and 0.76 (0.68–0.82) for algorithm B. Conclusion This study suggests the feasibility of automated CT-FFR, which can be performed on-site within several hours. However, the diagnostic performance of the current algorithm does not meet the a priori criteria for superiority. Future research is required to improve the accuracy.

Background: There has been no comparison of the determinants of admission route between acute ischemic stroke (AIS) and acute myocardial infarction (AMI). We examined whether factors associated with direct versus transferred-in admission to regional cardiocerebrovascular centers (RCVCs) differed between AIS and AMI. Methods: Using a nationwide RCVC registry, we identified consecutive patients presenting with AMI and AIS between July 2016 and December 2018. We explored factors associated with direct admission to RCVCs in patients with AIS and AMI and examined whether those associations differed between AIS and AMI, including interaction terms between each factor and disease type in multivariable models. To explore the influence of emergency medical service (EMS) paramedics on hospital selection, stratified analyses according to use of EMS were also performed. Results: Among the 17,897 and 8,927 AIS and AMI patients, 66.6% and 48.2% were directly admitted to RCVCs, respectively. Multivariable analysis showed that previous coronary heart disease, prehospital awareness, higher education level, and EMS use increased the odds of direct admission to RCVCs, but the odds ratio (OR) was different between AIS and AMI (for the first 3 factors, AMI > AIS; for EMS use, AMI < AIS). EMS use was the single most important factor for both AIS and AMI (OR, 4.72 vs. 3.90). Hypertension and hyperlipidemia increased, while living alone decreased the odds of direct admission only in AMI;additionally, age (65–74 years), previous stroke, and presentation during non-working hours increased the odds only in AIS. EMS use weakened the associations between direct admission and most factors in both AIS and AMI. Conclusions Various patient factors were differentially associated with direct admission to RCVCs between AIS and AMI. Public education for symptom awareness and use of EMS is essential in optimizing the transportation and hospitalization of patients with AMI and AIS.