68Ga-FAPI PET in Visualizing Acute Ischemic Stroke at Risk of Hemorrhagic Transformation.

ABSTRACT: Hemorrhagic transformation is a serious complication of ischemic stroke, which occurs at a rate of between 18% and 42%. 68Ga-FAPI PET can visualize acute cerebral infarction at risk of hemorrhagic transformation in the brain. We report a case of 68Ga-FAPI PET imaging in a patient with recurrent ischemic stroke. 68Ga-FAPI PET imaging revealed FAPI uptake in acute ischemic stroke with hemorrhagic transformation, but did not in some acute infarction and chronic infarction without hemorrhagic transformation. These findings suggest potential role of 68Ga-FAPI PET in the evaluation of acute ischemic stroke with the risk of hemorrhagic transformation.

Contemporary Statistics of Acute Ischemic Stroke and Transient Ischemic Attack in 2021: Insights From the CRCS-K-NIH Registry.

This report presents the latest statistics on the stroke population in South Korea, sourced from the Clinical Research Collaborations for Stroke in Korea-National Institute for Health (CRCS-K-NIH), a comprehensive, nationwide, multicenter stroke registry. The Korean cohort, unlike western populations, shows a male-to-female ratio of 1.5, attributed to lower risk factors in Korean women. The average ages for men and women are 67 and 73 years, respectively. Hypertension is the most common risk factor (67%), consistent with global trends, but there is a higher prevalence of diabetes (35%) and smoking (21%). The prevalence of atrial fibrillation (19%) is lower than in western populations, suggesting effective prevention strategies in the general population. A high incidence of large artery atherosclerosis (38%) is observed, likely due to prevalent intracranial arterial disease in East Asians and advanced imaging techniques. There has been a decrease in intravenous thrombolysis rates, from 12% in 2017-2019 to 10% in 2021, with no improvements in door-to-needle and door-to-puncture times, worsened by the coronavirus disease 2019 pandemic. While the use of aspirin plus clopidogrel for non-cardioembolic stroke and direct oral anticoagulants for atrial fibrillation is well-established, the application of direct oral anticoagulants for non-atrial fibrillation cardioembolic strokes in the acute phase requires further research. The incidence of early neurological deterioration (13%) and the cumulative incidence of recurrent stroke at 3 months (3%) align with global figures. Favorable outcomes at 3 months (63%) are comparable internationally, yet the lack of improvement in dependency at 3 months highlights the need for advancements in acute stroke care.

Effects of white matter hyperintensity burden on functional outcome after mild versus moderate-to-severe ischemic stroke.

It is uncertain whether the prognostic power of white matter hyperintensity (WMH) on post-stroke outcomes is modulated as a function of initial neurological severity, a critical determinant of outcome after stroke. This multi-center MRI study tested if higher WMH quintiles were associated with 3-month poor functional outcome (modified Rankin Scale ≥ 3) for mild versus moderate-to-severe ischemic stroke. Mild and moderate-to-severe stroke were defined as admission National Institute of Health Stroke Scale scores of 1-4 and ≥ 5, respectively. Mean age of the enrolled patients (n = 8918) was 67.2 ± 12.6 years and 60.1% male. The association between WMH quintiles and poor functional outcome was modified by stroke severity (p-for-interaction = 0.008). In mild stroke (n = 4994), WMH quintiles associated with the 3-month outcome in a dose-dependent manner for the 2nd to 5th quintile versus the 1st quintile, with adjusted-odds-ratios (aOR [95% confidence interval]) being 1.29 [0.96-1.73], 1.37 [1.02-1.82], 1.60 [1.19-2.13], and 1.89 [1.41-2.53], respectively. In moderate-to-severe stroke (n = 3924), however, there seemed to be a threshold effect: only the highest versus the lowest WMH quintile was significantly associated with poor functional outcome (aOR 1.69 [1.29-2.21]). WMH burden aggravates 3-month functional outcome after mild stroke, but has a lesser modulatory effect for moderate-to-severe stroke, likely due to saturation effects.

Focused magnetic stimulation for motor recovery after stroke.

BACKGROUND AND OBJECTIVES: The effects of noninvasive focused magnetothermal brain stimulation using magnetic nanoparticles (MNPs) on post-stroke motor deficits and metabolic dormancy in subacute ischemic injury are not well-established. This study examined if magnetothermal brain stimulation using magnetic nanoparticles (Nano-MS) enhances motor recovery after stroke. METHODS: We randomly distributed rats into Sham, Control, MNP injection only, and Nano-MS groups. We administered focused magnetic stimulation for 30 min daily following an MNP injection (15 mg/mL) into the targeted motor cortex via the carotid artery three weeks after the transient (90 min) middle cerebral artery occlusion. We assessed motor functionality via behavioral tests and conducted positron emission tomography (PET) imaging to verify cerebral metabolic activity. We assessed neuronal excitability, neuroinflammation, blood-brain barrier (BBB) integrity, and neurogenesis four weeks post-stroke. RESULTS: The Nano-MS group exhibited significantly improved motor deficits and cerebral metabolic activity compared to the Control and MNP groups (p < 0.05). Focused Nano-MS modulated neuronal excitability, evident by a depolarized action potential threshold for spike initiation and reduced firing frequency post-stroke. The Nano-MS group demonstrated markedly decreased inflammatory markers, such as IL-1ß, IL-6, TNF-α, MCP-1, and ICAM-1, compared to the Control and MNP groups. BBB integrity and immunofluorescence for neurogenesis markers were substantially improved in the Nano-MS group. CONCLUSIONS: Focused Nano-MS facilitates the recovery of motor deficits and metabolic inactivity in the brain by effectively modulating excitability, reducing neuroinflammation, enhancing BBB stability, and promoting neurogenesis. Nano-MS is a potential novel, noninvasive therapy for stroke rehabilitation. Further investigation is warranted.

Secular Trends in Outcomes and Impact of Novel Oral Anticoagulants in Atrial Fibrillation-Related Acute Ischemic Stroke.

BACKGROUND: Novel oral anticoagulants (NOACs) are currently recommended for the secondary prevention of stroke in patients with acute ischemic stroke (AIS) accompanied by atrial fibrillation (AF). However, the impact of NOACs on clinical outcomes in real-world practice remains ambiguous. This study analyzes the trend of clinical events in patients with AF-related AIS and determines how much the introduction of NOACs has mediated this trend. METHODS: We identified patients with AIS and AF between January 2011 and December 2019 using a multicenter stroke registry. Annual rates of NOAC prescriptions and clinical events within 1 year were evaluated. The primary outcome was a composite of recurrent stroke, myocardial infarction, and all-cause mortality. To assess the mediation effect of NOACs on the relationship between the calendar year and these outcomes, we used natural effect models and conducted exposure-mediator, exposure-outcome, and mediator-outcome analyses using multivariable regression models or accelerated failure time models, adjusting for potential confounders. RESULTS: Among the 12 977 patients with AF-related AIS, 12 500 (average age: 74.4 years; 51.3% male) were analyzed after excluding cases of valvular AF. Between 2011 and 2019, there was a significant decrease in the 1-year incidence of the primary composite outcome from 28.3% to 21.7%, while the NOAC prescription rate increased from 0% to 75.6%. A 1-year increase in the calendar year was independently associated with delayed occurrence of the primary outcome (adjusted time ratio, 1.10 [95% CI, 1.07-1.14]) and increased NOAC prescription (adjusted odds ratio, 2.20 [95% CI, 2.14-2.27]). Increased NOAC prescription was associated with delayed occurrence of the primary outcome (adjusted time ratio, 3.82 [95% CI, 3.17 to 4.61]). Upon controlling for NOAC prescription (mediator), the calendar year no longer influenced the primary outcome (adjusted time ratio, 0.97 [95% CI, 0.94-1.00]). This suggests that NOAC prescription mediates the association between the calendar year and the primary outcome. CONCLUSIONS: Our study highlights a temporal reduction in major clinical events or death in Korean patients with AF-related AIS, mediated by increased NOAC prescription, emphasizing NOAC use in this population.

Treatment of Ischemic Stroke by Atorvastatin-Loaded PEGylated Liposome.

There is insufficient evidence on the effect of nanoparticles, particularly liposomes loaded with a statin, on acute ischemic stroke. We investigated the impact of atorvastatin-loaded PEG (polyethylene glycol) conjugated liposomes (LipoStatin) on the outcomes in rats with cerebral ischemia-reperfusion. PEGylated liposome loaded with atorvastatin was developed as a nanoparticle to specifically accumulate in an ischemic region and release the drug to ameliorate the harmful effects of the stroke. LipoStatin was administered to rats with transient middle cerebral artery occlusion through the tail vein immediately after reperfusion (LipoStatin group). LipoStatin efficiently accumulated at the cerebral ischemic injury site of the rat. The LipoStatin group showed a significantly reduced infarct volume (p < 0.01) in brain micro-MR imaging and improved neurological function recovery compared to the control group (p < 0.05). In addition, markedly improved brain metabolism using fluorine-18 fluorodeoxyglucose micro-PET/CT imaging was demonstrated in the LipoStatin group compared with the control group (p < 0.01). Mechanistically, as a result of evaluation through IL-1 beta, TNF-alpha, ICAM-1, and Iba-1 mRNA expression levels at 5 days after cerebral ischemia, LipoStatin showed significant anti-inflammatory effects. Protein expression of occludin, JAM-A, Caveolin-1, and eNOS by western blot at 3 days and fluorescent images at 7 days showed considerable recovery of blood-brain barrier breakdown and endothelial dysfunction. PEGylated LipoStatin can be more effectively delivered to the ischemic brain and may have significant neuroprotective effects. Thus, PEGylated LipoStatin can be further developed as a promising targeted therapy for ischemic stroke and other major vascular diseases.

Improvement in Delivery of Ischemic Stroke Treatments but Stagnation of Clinical Outcomes in Young Adults in South Korea.

BACKGROUND: There is limited information on the delivery of acute stroke therapies and secondary preventive measures and clinical outcomes over time in young adults with acute ischemic stroke. This study investigated whether advances in these treatments improved outcomes in this population. METHODS: Using a prospective multicenter stroke registry in Korea, young adults (aged 18-50 years) with acute ischemic stroke hospitalized between 2008 and 2019 were identified. The observation period was divided into 4 epochs: 2008 to 2010, 2011 to 2013, 2014 to 2016, and 2017 to 2019. Secular trends for patient characteristics, treatments, and outcomes were analyzed. RESULTS: A total of 7050 eligible patients (mean age, 43.1; men, 71.9%) were registered. The mean age decreased from 43.6 to 42.9 years (Ptrend=0.01). Current smoking decreased, whereas obesity increased. Other risk factors remained unchanged. Intravenous thrombolysis and mechanical thrombectomy rates increased over time from 2008 to 2010 to 2017 to 2019 (9.5%-13.8% and 3.2%-9.2%, respectively; Ptrend<0.01). Door-to-needle time improved (Ptrend <.001), but onset-to-door and door-to-puncture times remained constant. Secondary prevention, including dual antiplatelets for noncardioembolic minor stroke (26.7%-47.0%), direct oral anticoagulants for atrial fibrillation (0.0%-56.2%), and statins for large artery atherosclerosis (76.1%-95.3%) increased (Ptrend<0.01). Outcome data were available from 2011. One-year mortality (2.5% in 2011-2013 and 2.3% in 2017-2019) and 3-month modified Rankin Scale scores 0 to 1 (68.3%-69.1%) and 0 to 2 (87.6%-86.2%) remained unchanged. The 1-year stroke recurrence rate increased (4.1%-5.5%; Ptrend=0.04), although the difference was not significant after adjusting for sex and age. CONCLUSIONS: Improvements in the delivery of acute stroke treatments did not necessarily lead to better outcomes in young adults with acute ischemic stroke over the past decade, indicating a need for further progress.

Statin Treatment in Patients With Stroke With Low-Density Lipoprotein Cholesterol Levels Below 70 mg/dL.

Background It is unclear whether statin treatment could reduce the risk of early vascular events when baseline low-density lipoprotein cholesterol (LDL-C) levels are already low, at <70 mg/dL, at the time of the index stroke. Methods and Results This study was an analysis of a prospective, multicenter, nationwide registry of consecutive patients with first-ever acute ischemic stroke with baseline low-density lipoprotein cholesterol levels <70 mg/dL and without statin pretreatment. An inverse probabilities of treatment weights method was applied to control for imbalances in baseline characteristics. The primary outcome was a composite of stroke (either hemorrhagic or ischemic), myocardial infarction, and all-cause death within 3 months. A total of 2850 patients (age, 69.5±13.4 years; men, 63.5%) were analyzed for this study. In-hospital statin treatment was used for 74.2% of patients. The primary composite outcome within 3 months occurred in 21.5% of patients in the nonstatin group and 6.7% of patients in the statin group (P<0.001), but the rates of stroke (2.65% versus 2.33%), hemorrhagic stroke (0.16% versus 0.10%), and myocardial infarction (0.73% versus 0.19%) were not significantly different between the 2 groups. After inverse probability of treatment weighting analysis, the primary composite outcome was significantly reduced in patients with statin therapy (weighted hazard ratio [HR], 0.54 [95% CI, 0.42-0.69]). However, statin treatment did not increase the risk of hemorrhagic stroke (weighted HR, 1.11 [95% CI, 0.10-12.28]). Conclusions Approximately three-quarters of the patients with first-ever ischemic stroke with baseline low-density lipoprotein cholesterol levels <70 mg/dL received in-hospital statin treatment. Statin treatment, compared with no statin treatment, was significantly associated with a reduced risk of the 3-month primary composite outcomes and all-cause death but did not alter the rate of stroke recurrence.

Admission LDL-cholesterol, statin pretreatment and early outcomes in acute ischemic stroke.

BACKGROUND: Lipid paradox of low LDL-C may cause physicians to be reluctant to use statins in acute ischemic stroke (AIS) patients with low LDL-C levels at admission. OBJECTIVE: This study investigated the association between LDL-C levels and early vascular outcomes and assessed the potential interaction effect between LDL-C and statin pretreatment on early outcomes. PATIENTS AND METHODS: This was a study of a prospective, multicenter, registry of AIS patients with admission LDL-C. The subjects were divided into 3 groups according to LDL-C levels: low LDL-C (≤100 mg/dL); intermediate LDL-C (>100, <130 mg/dL); and high LDL-C (≥130 mg/dL). The primary early vascular outcome was a composite of stroke (ischemic or hemorrhagic), myocardial infarction and all-cause mortality within 3 months. The associations of LDL-C levels as a continuous variable and the risks of primary outcome using Cox proportional hazards models with restricted cubic splines were explored. RESULTS: A total of 32,505 patients (age, 69 ± 12; male, 58.6%) were analyzed. The 3 groups showed significant differences in the 3-month primary outcome, with highest events in the low LDL-C group; after adjustment, no significant associations with the 3-month primary outcome remained. U-shaped nonlinear relationships of LDL-C levels with the 3-month primary outcome were observed (Pnon-linearity<0.001), with substantial relationships in the no pretreatment subgroup. CONCLUSIONS: The relationships between admission LDL-C levels and early outcomes are complex but appear to be paradoxical in patients with low LDL-C and no statin pretreatment. The results suggest that statin pretreatment might offset the paradoxical response of low LDL-C on early vascular outcomes. Further study would be warranted.

D-dimer to fibrinogen ratio predicts early neurological deterioration in ischemic stroke with atrial fibrillation.

INTRODUCTION: The D-dimer to fibrinogen ratio (DFR) is a good indicator of clot-producing activity in thrombotic disease, but its clinical usefulness in stroke patients with nonvalvular atrial fibrillation (NVAF) has not been studied. We evaluated the association between the DFR and early neurological deterioration (END) in acute ischemic stroke (AIS) patients with NVAF. METHODS: We included consecutive AIS patients with NVAF between 2013 and 2015 from the registry of a real-world prospective cohort from 11 large centers in South Korea. END was defined as an increase ≥2 in the total NIHSS score or ≥ 1 in the motor NIHSS score within the first 72 h of admission. The DFR was calculated as follows: DFR = D-dimer (mg/L)/fibrinogen (mg/dL) x 100. RESULTS: A total of 1018 AIS patients with NVAF were evaluated. In multivariable logistic regression analysis, the highest DFR tertile was closely associated with END (adjusted odds ratio [aOR] = 2.14, 95 % confidence interval [CI]: 1.24-3.69). Hypertension (aOR = 1.71, 95 % CI: 1.09-2.70), initial NIHSS score (aOR = 1.05, 95 % CI: 1.02-1.07) and use of anticoagulants (aOR = 0.41, 95 % CI: 0.28-0.60) were also correlated with END. In addition to END, the DFR was correlated with discharge NIHSS and modified Rankin Scale (mRS) scores and the 3-month mRS score. CONCLUSIONS: High DFR values were associated with END in AIS patients with NVAF. As the DFR is an indicator directly related to the main pathological mechanism of NVAF patients (fibrinolysis and coagulation), it may be useful in predicting their prognosis.

Comparison of Hospital Performance in Acute Ischemic Stroke Based on Mortality and Functional Outcome in South Korea.

BACKGROUND: Recent evidence suggests a correlation between modified Rankin Scale-based measures, an outcome measure commonly used in acute stroke trials, and mortality-based measures used by health agencies in the evaluation of hospital performance. We aimed to examine whether the 2 types of measures are interchangeable in relation to evaluation of hospital performance in acute ischemic stroke. METHODS: Five outcome measures, unfavorable functional outcome (3-month modified Rankin Scale score ≥2), death or dependency (3-month modified Rankin Scale score ≥3), 1-month mortality, 3-month mortality, and 1-year mortality, were collected for 8292 individuals who were hospitalized for acute ischemic stroke between January 2014 and May 2015 in 14 hospitals participating in the Clinical Research Collaboration for Stroke in Korea - National Institute of Health registry. Hierarchical regression models were used to calculate per-hospital risk-adjusted outcome rates for each measure. Hospitals were ranked and grouped based on the risk-adjusted outcome rates, and the correlations between the modified Rankin Scale-based and mortality-based ranking and their intermeasure reliability in categorizing hospital performance were analyzed. RESULTS: The comparison between the ranking based on the unfavorable functional outcome and that based on 1-year mortality resulted in a Spearman correlation coefficient of -0.29 and Kendall rank coefficient of -0.23, and the comparison of grouping based on these 2 types of ranks resulted in a weighted kappa of 0.123 for the grouping in the top 33%/middle 33%/bottom 33% and 0.25 for the grouping in the top 20%/middle 60%/bottom 20%, respectively. No significant correlation or similarity in grouping capacities were found between the rankings based on the functional outcome measures and those based on the mortality measures. CONCLUSIONS: This study shows that regardless of clinical correlation at an individual patient level, functional outcome-based measures and mortality-based measures are not interchangeable in the evaluation of hospital performance in acute ischemic stroke.

Biological Mechanism of Sex Difference in Stroke Manifestation and Outcomes.

BACKGROUND AND OBJECTIVES: Female patients tend to have greater disability and worse long-term outcomes after stroke than male patients. To date, the biological basis of sex difference in ischemic stroke remains unclear. We aimed to (1) assess sex differences in clinical manifestation and outcomes of acute ischemic stroke and (2) investigate whether the sex disparity is due to different infarct locations or different impacts of infarct in the same location. METHODS: This MRI-based multicenter study included 6,464 consecutive patients with acute ischemic stroke (<7 days) from 11 centers in South Korea (May 2011-January 2013). Multivariable statistical and brain mapping methods were used to analyze clinical and imaging data collected prospectively: admission NIH Stroke Scale (NIHSS) score, early neurologic deterioration (END) within 3 weeks, modified Rankin Scale (mRS) score at 3 months, and culprit cerebrovascular lesion (symptomatic large artery steno-occlusion and cerebral infarction) locations. RESULTS: The mean (SD) age was 67.5 (12.6) years, and 2,641 (40.9%) were female patients. Percentage infarct volumes on diffusion-weighted MRI did not differ between female patients and male patients (median 0.14% vs 0.14%, p = 0.35). However, female patients showed higher stroke severity (NIHSS score, median 4 vs 3, p < 0.001) and had more frequent END (adjusted difference 3.5%; p = 0.002) than male patients. Female patients had more frequent striatocapsular lesions (43.6% vs 39.8%, p = 0.001) and less frequent cerebrocortical (48.2% vs. 50.7% in patients older than 52 years, p = 0.06) and cerebellar (9.1% vs. 11.1%, p = 0.009) lesions than male patients, which aligned with angiographic findings: female patients had more prevalent symptomatic steno-occlusion of the middle cerebral artery (MCA) (31.1% vs 25.3%; p < 0.001) compared with male patients, who had more frequent symptomatic steno-occlusion of the extracranial internal carotid artery (14.2% vs 9.3%; p < 0.001) and vertebral artery (6.5% vs 4.7%; p = 0.001). Cortical infarcts in female patients, specifically left-sided parieto-occipital regions, were associated with higher NIHSS scores than expected for similar infarct volumes in male patients. Consequently, female patients had a higher likelihood of unfavorable functional outcome (mRS score >2) than male patients (adjusted absolute difference 4.5%; 95% CI 2.0-7.0; p < 0.001). DISCUSSION: Female patients have more frequent MCA disease and striatocapsular motor pathway involvement with acute ischemic stroke, along with left parieto-occipital cortical infarcts showing greater severity for equivalent infarct volumes than in male patients. This leads to more severe initial neurologic symptoms, higher susceptibility to neurologic worsening, and less 3-month functional independence, when compared with male patients.

Magnetothermal-based non-invasive focused magnetic stimulation for functional recovery in chronic stroke treatment.

Magnetic heat-based brain stimulation of specific lesions could promote the restoration of impaired motor function caused by chronic stroke. We delivered localized stimulation by nanoparticle-mediated heat generation within the targeted brain area via focused magnetic stimulation. The middle cerebral artery occlusion model was prepared, and functional recovery in the chronic-phase stroke rat model was demonstrated by the therapeutic application of focused magnetic stimulation. We observed a transient increase in blood-brain barrier permeability at the target site of < 4 mm and metabolic brain activation at the target lesion. After focused magnetic stimulation, the rotarod score increased by 390 ± 28% (p < 0.05) compared to the control group. Standardized uptake value in the focused magnetic stimulation group increased by 2063 ± 748% (p < 0.01) compared to the control group. Moreover, an increase by 24 ± 5% (p < 0.05) was observed in the sham group as well. Our results show that non-invasive focused magnetic stimulation can safely modulate BBB permeability and enhance neural activation for chronic-phase stroke treatment in the targeted deep brain area.

Dual antiplatelet Use for extended period taRgeted to AcuTe ischemic stroke with presumed atherosclerotic OrigiN (DURATION) trial: Rationale and design.

RATIONALE: The optimal duration of dual antiplatelet therapy (DAPT) with clopidogrel-aspirin for the large artery atherosclerotic (LAA) stroke subtype has been debated. AIMS: To determine whether the 1-year risk of recurrent vascular events could be reduced by a longer duration of DAPT in patients with the LAA stroke subtype. METHODS AND STUDY DESIGN: A total of 4806 participants will be recruited to detect a statistically significant relative risk reduction of 22% with 80% power and a two-sided alpha error of 0.05, including a 10% loss to follow-up. This is a registry-based, multicenter, prospective, randomized, open-label, blinded end point study designed to evaluate the efficacy and safety of a 12-month duration of DAPT compared with a 3-month duration of DAPT in the LAA stroke subtype. Patients will be randomized (1:1) to either DAPT for 12 months or DAPT for 3 months, followed by monotherapy (either aspirin or clopidogrel) for the remaining 9 months. STUDY OUTCOMES: The primary efficacy outcome of the study is a composite of stroke (ischemic or hemorrhagic), myocardial infarction, and all-cause mortality for 1 year after the index stroke. The secondary efficacy outcomes are (1) stroke, (2) ischemic stroke or transient ischemic attack, (3) hemorrhagic stroke, and (4) all-cause mortality. The primary safety outcome is major bleeding. DISCUSSION: This study will help stroke physicians determine the appropriate duration of dual therapy with clopidogrel-aspirin for patients with the LAA stroke subtype. TRIAL REGISTRATION: URL: https://cris.nih.go.kr/cris. CRIS Registration Number: KCT0004407.

Deep learning-based personalised outcome prediction after acute ischaemic stroke.

BACKGROUND: Whether deep learning models using clinical data and brain imaging can predict the long-term risk of major adverse cerebro/cardiovascular events (MACE) after acute ischaemic stroke (AIS) at the individual level has not yet been studied. METHODS: A total of 8590 patients with AIS admitted within 5 days of symptom onset were enrolled. The primary outcome was the occurrence of MACEs (a composite of stroke, acute myocardial infarction or death) over 12 months. The performance of deep learning models (DeepSurv and Deep-Survival-Machines (DeepSM)) and traditional survival models (Cox proportional hazards (CoxPH) and random survival forest (RSF)) were compared using the time-dependent concordance index ([Formula: see text] index). RESULTS: Given the top 1 to all 60 clinical factors according to feature importance, CoxPH and RSF yielded [Formula: see text] index of 0.7236-0.8222 and 0.7279-0.8335, respectively. Adding image features improved the performance of deep learning models and traditional models assisted by deep learning models. DeepSurv and DeepSM yielded the best [Formula: see text] index of 0.8496 and 0.8531 when images were added to all 39 relevant clinical factors, respectively. In feature importance, brain image was consistently ranked highly. Deep learning models automatically extracted the image features directly from personalised brain images and predicted the risk and date of future MACEs at the individual level. CONCLUSIONS: Deep learning models using clinical data and brain images could improve the prediction of MACEs and provide personalised outcome prediction for patients with AIS. Deep learning models will allow us to develop more accurate and tailored prognostic prediction systems that outperform traditional models.

Admission hyperglycemia, stroke subtypes, outcomes in acute ischemic stroke.

AIMS: Whether admission hyperglycemia is differentially associated with early vascular outcomes in acute ischemic stroke (AIS) depending on stroke subtype has been incompletely delineated. METHODS: In a multicenter, prospective stroke registry, patients with AIS were categorized based on admission glucose levels into normoglycemia, moderate hyperglycemia, and severe hyperglycemia (<140mg/dl, 140-179mg/dl, and ≥180mg/dl, respectively) groups. Multivariate analysis assessed the interaction between the hyperglycemia and ischemic stroke subtypes of large artery atherothrombosis (LAA), cardioembolism (CE), and small vessel occlusion (SVO) and early vascular outcomes (3-month stroke, all-cause mortality, and composite of stroke, MI, and all-cause mortality). RESULTS: Among the 32,772 patients (age:69.0±12.6yrs, male:58.4%) meeting eligibility criteria, 61.9% were in the normoglycemia group, 19.5% were in the moderate hyperglycemia group, and 18.7% were in the severe hyperglycemia group. Substantial interactions between hyperglycemia groups and stroke subtypes were observed for 3-month stroke (Pinteraction = 0.003) and composite of stroke, MI, and all-cause mortality (Pinteraction = 0.001), with differential recurrence strongest among CE, intermediate among LAA, and least among SVO. CONCLUSIONS: Hyperglycemia was differently associated with the risk of 3-month stroke by ischemic stroke subtype. The associations of hyperglycemia with 3-month stroke were greatest in CE subtype but not in SVO subtype. These results suggest that the effect of glucose-lowering treatment after AIS may differ according to stroke subtype.

Covert Brain Infarction as a Risk Factor for Stroke Recurrence in Patients With Atrial Fibrillation.

BACKGROUND: We aimed to evaluate covert brain infarction (CBI), frequently encountered during the diagnostic work-up of acute ischemic stroke, as a risk factor for stroke recurrence in patients with atrial fibrillation (AF). METHODS: For this prospective cohort study, from patients with acute ischemic stroke hospitalized at 14 centers between 2017 and 2019, we enrolled AF patients without history of stroke or transient ischemic attack and divided them into the CBI (+) and CBI (-) groups. The 2 groups were compared regarding the 1-year cumulative incidence of recurrent ischemic stroke and all-cause mortality using the Fine and Gray subdistribution hazard model with nonstroke death as a competing risk and the Cox frailty model, respectively. Each CBI lesion was also categorized into either embolic-appearing (EA) or non-EA pattern CBI. Adjusted hazard ratios and 95% CIs of any CBI, EA pattern CBI only, non-EA pattern CBI only, and both CBIs were estimated. RESULTS: Among 1383 first-ever stroke patients with AF, 578 patients (41.8%) had CBI. Of these 578 with CBI, EA pattern CBI only, non-EA pattern CBI only, and both CBIs were 61.8% (n=357), 21.8% (n=126), and 16.4% (n=95), respectively. The estimated 1-year cumulative incidence of recurrent ischemic stroke was 5.2% and 1.9% in the CBI (+) and CBI (-) groups, respectively (P=0.001 by Gray test). CBI increased the risk of recurrent ischemic stroke (adjusted hazard ratio [95% CI], 2.91 [1.44-5.88]) but did not the risk of all-cause mortality (1.32 [0.97-1.80]). The EA pattern CBI only and both CBIs elevated the risk of recurrent ischemic stroke (2.76 [1.32-5.77] and 5.39 [2.25-12.91], respectively), while the non-EA pattern only did not (1.44 [0.40-5.16]). CONCLUSIONS: Our study suggests that AF patients with CBI might have increased risk of recurrent stroke. CBI could be considered when estimating the stroke risk in patients with AF.

Frequency, management, and outcomes of early neurologic deterioration due to stroke progression or recurrence.

OBJECTIVE: The frequency, management, and outcomes of early neurologic deterioration (END) after ischemic stroke specifically due to stroke progression or stroke recurrence have not been well delineated. MATERIALS AND METHODS: In a multicenter, nationwide registry, data on END due to stroke progression or recurrence confirmed by imaging were collected prospectively between January 2019 and July 2020. Patient characteristics, management strategies, and clinical outcomes were analyzed. RESULTS: Among 14,828 consecutive ischemic stroke patients, 1717 (11.6%) experienced END, including 1221 (8.2%) with END due to stroke progression (SP) or stroke recurrence (SR). Active management after END was implemented in 64.2% of patients. Active management strategies included volume expansion (29.2%), change in antithrombotic regimen (26.1%), induced hypertension (8.6%), rescue reperfusion therapy (6.8%), intracranial pressure lowering with hyperosmolar agents (1.5%), bypass surgery (0.6%), and hypothermia (0.1%). Active management strategies that varied with patient features included volume expansion and induced hypertension, used more often in large artery atherosclerosis and small vessel occlusion, and rescue endovascular thrombectomy, more common in other (dissection), cardioembolism, and large artery atherosclerosis. Active management was associated with higher rates of freedom from disability (modified Rankin Scale, mRS, 0-1; 24.3% vs. 16.6%) and functional independence (mRS, 0-2; 41.6% vs. 27.7%) at 3 months. CONCLUSION: END specifically due to stroke progression or recurrence occurs in 1 in 12 acute ischemic stroke patients. In this observational study, active management, undertaken in two-thirds of patients, was most often hemodynamic or antithrombotic and was associated with improved functional outcomes.

Predictors of long-term medication adherence in stroke survivors: A multicentre, prospective, longitudinal study.

BACKGROUND: Although the optimal use of prescribed medications for stroke survivors is critical for preventing secondary stroke, longitudinal observations of the natural course of medication persistence and adherence in Korean stroke survivors are rare. Furthermore, studies are needed to identify strong predictors influencing medication adherence and to determine whether these predictors change over time. AIMS AND OBJECTIVES: To evaluate the longitudinal medication persistence and adherence at 3 months and 1 year after discharge in all stroke patients and to identify predictors of long-term medication adherence in patients who can self-medicate. DESIGN: A multicentre, prospective, longitudinal descriptive study. METHODS: A total of 600 consecutive ischaemic stroke patients were recruited from three stroke centres across Korea, from 1 September, 2017 to 28 February, 2019. Various factors related to medication adherence suggested by the World Health Organisation were investigated through face-to-face interviews at each centre during hospitalisation. Medication persistence and adherence were assessed at 3 months and 1 year after discharge using the eight-item Morisky Medication Adherence Scale through telephone interviews. RESULTS: Of 537 survivors at 3 months, 526 (98.0%) were persistent and 472 (89.7%) were adherent. Of 493 survivors at 1 year, 477 (96.8%) were persistent and 392 (82.2%) were adherent. Medication belief, income and health literacy were statistically significant predictors of three-month medication adherence, which predicted one-year medication adherence with older age and low income. CONCLUSIONS: Among Korean stroke survivors, three-month and one-year medication persistence and adherence were relatively good. Medication beliefs and three-month medication adherence were important and modifiable factors predicting three-month adherence and one-year adherence, respectively. RELEVANCE TO CLINICAL PRACTICE: To increase long-term adherence to medication, various strategies are needed to improve beliefs about medication, taking into account the patient's age and level of knowledge. These interventions need to be initiated during hospitalisation to form early medication habits after discharge.