Hypomethylation in MTNR1B: a novel epigenetic marker for atherosclerosis profiling using stenosis radiophenotype and blood inflammatory cells.

BACKGROUND: Changes in gene-specific promoter methylation may result from aging and environmental influences. Atherosclerosis is associated with aging and environmental effects. Thus, promoter methylation profiling may be used as an epigenetic tool to evaluate the impact of aging and the environment on atherosclerosis development. However, gene-specific methylation changes are currently inadequate epigenetic markers for predicting atherosclerosis and cardiovascular disease pathogenesis. RESULTS: We profiled and validated changes in gene-specific promoter methylation associated with atherosclerosis using stenosis radiophenotypes of cranial vessels and blood inflammatory cells rather than direct sampling of atherosclerotic plaques. First, we profiled gene-specific promoter methylation changes using digital restriction enzyme analysis of methylation (DREAM) sequencing in peripheral blood mononuclear cells from eight samples each of cranial vessels with and without severe-stenosis radiophenotypes. Using DREAM sequencing profiling, 11 tags were detected in the promoter regions of the ACVR1C, ADCK5, EFNA2, ENOSF1, GLS2, KNDC1, MTNR1B, PACSIN3, PAX8-AS1, TLDC1, and ZNF7 genes. Using methylation evaluation, we found that EFNA2, ENOSF1, GLS2, KNDC1, MTNR1B, PAX8-AS1, and TLDC1 showed > 5% promoter methylation in non-plaque intima, atherosclerotic vascular tissues, and buffy coats. Using logistic regression analysis, we identified hypomethylation of MTNR1B as an independent variable for the stenosis radiophenotype prediction model by combining it with traditional atherosclerosis risk factors including age, hypertension history, and increases in creatinine, lipoprotein (a), and homocysteine. We performed fivefold cross-validation of the prediction model using 384 patients with ischemic stroke (50 [13%] no-stenosis and 334 [87%] > 1 stenosis radiophenotype). For the cross-validation, the training dataset included 70% of the dataset. The prediction model showed an accuracy of 0.887, specificity to predict stenosis radiophenotype of 0.940, sensitivity to predict no-stenosis radiophenotype of 0.533, and area under receiver operating characteristic curve of 0.877 to predict stenosis radiophenotype from the test dataset including 30% of the dataset. CONCLUSIONS: We identified and validated MTNR1B hypomethylation as an epigenetic marker to predict cranial vessel atherosclerosis using stenosis radiophenotypes and blood inflammatory cells rather than direct atherosclerotic plaque sampling.

Comparison of Factors Associated With Direct Versus Transferred-in Admission to Government-Designated Regional Centers Between Acute Ischemic Stroke and Myocardial Infarction in Korea.

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.

Comparisons of Prehospital Delay and Related Factors Between Acute Ischemic Stroke and Acute Myocardial Infarction.

Background Prehospital delay is an important contributor to poor outcomes in both acute ischemic stroke (AIS) and acute myocardial infarction (AMI). We aimed to compare the prehospital delay and related factors between AIS and AMI. Methods and Results We identified patients with AIS and AMI who were admitted to the 11 Korean Regional Cardiocerebrovascular Centers via the emergency room between July 2016 and December 2018. Delayed arrival was defined as a prehospital delay of >3 hours, and the generalized linear mixed-effects model was applied to explore the effects of potential predictors on delayed arrival. This study included 17 895 and 8322 patients with AIS and AMI, respectively. The median value of prehospital delay was 6.05 hours in AIS and 3.00 hours in AMI. The use of emergency medical services was the key determinant of delayed arrival in both groups. Previous history, 1-person household, weekday presentation, and interhospital transfer had higher odds of delayed arrival in both groups. Age and sex had no or minimal effects on delayed arrival in AIS; however, age and female sex were associated with higher odds of delayed arrival in AMI. More severe symptoms had lower odds of delayed arrival in AIS, whereas no significant effect was observed in AMI. Off-hour presentation had higher and prehospital awareness had lower odds of delayed arrival; however, the magnitude of their effects differed quantitatively between AIS and AMI. Conclusions The effects of some nonmodifiable and modifiable factors on prehospital delay differed between AIS and AMI. A differentiated strategy might be required to reduce prehospital delay.

Apixaban for Secondary Stroke Prevention: Coexistant Cerebral Atherosclerosis May Increase Recurrent Strokes.

BACKGROUND AND PURPOSE: Oral anticoagulants are needed in stroke patients with atrial fibrillation (AF) for the prevention of recurrent stroke. However, the risk of major events or bleeding may be greater in stroke patients than in those without, because the presence of cerebral atherosclerosis or small vessel disease may increase these risks. This study aimed to investigate the outcomes of apixaban-treated stroke patients with AF and assess whether these factors are associated with the outcome. METHODS: This was a sub-analysis of stroke patients with AF enrolled in a prospective, open-label, multicenter, post-marketing surveillance study in South Korea, who were treated with apixaban and underwent magnetic resonance imaging (MRI) (Clinical trial registration: NCT01885598). RESULTS: A total of 651 patients (mean age, 72.5±8.7 years) received apixaban for a mean duration of 82.7±37.4 weeks. Fifty-three bleeding events occurred in 39 patients (6.0%), and 10 (1.5%) experienced major bleeding. Seventeen patients (2.6%) had major events (stroke, n=15, 2.3%; all ischemic), systemic embolism (n=1, 0.2%), and death (n=3, 0.5%). MRI data showed no significant association between white matter ischemic changes and microbleeds, and major events or bleeding. Patients with cerebral atherosclerotic lesions had a higher rate of major events than those without (4.6% [n=10/219] vs. 1.7% [n=7/409], P=0.0357), which partly explains the increased prevalence of major outcomes in this group versus patients without stroke (0.7%, P=0.0002). CONCLUSIONS: Apixaban is generally safe for patients with ischemic stroke. Increased primary outcomes in stroke patients may in part be attributed to the presence of cerebral atherosclerotic lesions, suggesting that further studies are needed to establish therapeutic strategies in this population.

Effect of bioactive glass addition on the physical properties of mineral trioxide aggregate.

BACKGROUND: The addition of bioactive glass (BG), a highly bioactive material with remineralization potential, might improve the drawback of weakening property of mineral trioxide aggregates (MTA) when it encounters with body fluid. This study aims to evaluate the effect of BG addition on physical properties of MTA. METHODS: ProRoot (MTA), and MTA with various concentrations of BG (1, 2, 5 and 10% BG/MTA) were prepared. Simulated body fluid (SBF) was used to investigate the effect of the storage solution on dentin remineralization. Prepared specimens were examined as following; the push-out bond strength to dentin, compressive strength, setting time solubility and X-ray diffraction (XRD) analysis. RESULTS: The 2% BG/MTA showed higher push-out bond strengths than control group after 7 days of SBF storage. The 2% BG/MTA exhibited the highest compressive strength. Setting times were reduced in the 1 and 2% BG/MTA groups, and solubility of all experimental groups were clinically acceptable. In all groups, precipitates were observed in dentinal tubules via SEM. XRD showed the increased hydroxyapatite peaks in the 2, 5 and 10% BG/MTA groups. CONCLUSION: It was verified that the BG-added MTA increased dentin push-out bond strength and compressive strength under SBF storage. The addition of BG did not negatively affect the MTA maturation reaction; it increased the amount of hydroxyapatite during SBF maturation.

Post-Stroke Depressive Symptoms: Varying Responses to Escitalopram by Individual Symptoms and Lesion Location.

OBJECTIVE: The efficacy of antidepressants in post-stroke depressive symptoms (PSD) varies. We aimed to examine whether the effect of escitalopram on PSD differs according to individual depressive symptoms and stroke lesion location. METHODS: This is a post hoc analysis of EMOTION (ClinicalTrials.gov, NCT01278498), a randomized, placebo-controlled, double-blind trial that examined the efficacy of escitalopram on depression in acute stroke patients (237 with placebo, 241 with escitalopram). Depressive symptoms were evaluated with the 10-item Montgomery-Åsberg Depression Rating Scale (MADRS). Changes in MADRS and individual item scores at 12 weeks were compared between the treatment groups and among the stroke lesion location groups. Stroke lesion locations were grouped according to the anatomical distribution of serotonin fibers that originate from the midbrain/pons and spread to the forebrain via subcortical structures: "Midbrain-Pons," "Frontal-Subcortical," and "Others." Least-squares means were calculated to demonstrate the independent effect of lesion location. RESULTS: Total MADRS scores decreased more significantly in the escitalopram than in the placebo group, while a significant effect of escitalopram was observed in only 3 items: apparent sadness, reported sadness, pessimistic thoughts. In the lesion location analyses, escitalopram users in the Frontal-Subcortical group showed significant improvement in total MADRS scores (placebo [n = 130] vs. escitalopram [n = 148], least-square mean [95% CI]: -2.3 [-3.5 to -0.2] vs. -4.5 [-5.5 to -3.4], p = .005), while those in the Midbrain-Pons and Others groups did not. CONCLUSIONS: The effect of escitalopram on PSD may be more prominent in patients with particular depressive symptoms and stroke lesion locations, suggesting the need for tailored treatment strategies.

Bleaching toothpaste with two different concentrations of hydrogen peroxide: A randomized double-blinded clinical trial.

OBJECTIVES: This randomized double-blinded clinical trial evaluated the bleaching efficacy and incidence of contact hypersensitivity of three kinds of bleaching toothpaste. METHODS: Forty-nine participants above A2 shade on the maxillary central incisor (#11) and canine (#13) were randomized into three groups: TW group (n = 15), 0.75 % HP-containing toothpaste (Toothwhole white); VL group (n = 15), 0.75 % HP-containing toothpaste (Vussen 7); and VH group (n = 17), 2.8 % of HP-containing toothpaste (Vussen 28). Participants were instructed to manually brush their teeth for 3 min, 3 times per day for 12 weeks. They were followed-up after 4 and 12 weeks. Shade measurements were performed using a spectrophotometer (SP), and data were calculated with CIELab (ΔEab*) and CIEDE2000 (ΔE00) formula. Additionally, visual inspection (VI) using the Vitapan classical shade guide was also performed, and the correlation between the two measurements was analyzed by comparing the CIELab (ΔEab*) values. The incidence of contact hypersensitivity at each follow-up was recorded. A mixed-effect model was performed to assess shade changes and chi-square tests for the incidence of contact hypersensitivity, respectively. RESULTS: At 12 week follow-up, all groups showed ΔEab* above 3.46, and ΔE00 above 2.25 for tooth #11. For tooth #13, the ΔEab* and ΔE00 of VH and TW groups only were above those thresholds. Shade change varied according to toothpaste and follow-up points. SP and VI showed a moderate positive correlation for L*, a*, and b*, respectively (P < 0.05). Contact hypersensitivity was not significantly different among the groups (P > 0.05). CONCLUSIONS: Bleaching toothpaste with higher HP yields a better shade change than other toothpaste after 12 weeks. CLINICAL SIGNIFICANCE: The use of bleaching toothpaste with a higher HP concentration results in a better shade improvement.

Promoter methylation changes in ALOX12 and AIRE1: novel epigenetic markers for atherosclerosis.

BACKGROUND: Atherosclerosis is the main cause of cardiovascular diseases such as ischemic stroke and coronary heart disease. Gene-specific promoter methylation changes have been suggested as one of the causes underlying the development of atherosclerosis. We aimed to identify and validate specific genes that are differentially expressed through promoter methylation in atherosclerotic plaques. We performed the present study in four steps: (1) profiling and identification of gene-specific promoter methylation changes in atherosclerotic tissues; (2) validation of the promoter methylation changes of genes in plaques by comparison with non-plaque intima; (3) evaluation of promoter methylation status of the genes in vascular cellular components composing atherosclerotic plaques; and (4) evaluation of promoter methylation differences in genes among monocytes, T cells, and B cells isolated from the blood of ischemic stroke patients. RESULTS: Upon profiling, AIRE1, ALOX12, FANK1, NETO1, and SERHL2 were found to have displayed changes in promoter methylation. Of these, AIRE1 and ALOX12 displayed higher methylation levels in plaques than in non-plaque intima, but lower than those in the buffy coat of blood. Between inflammatory cells, the three genes were significantly less methylated in monocytes than in T and B cells. In the vascular cells, AIRE1 methylation was lower in endothelial and smooth muscle cells. ALOX12 methylation was higher in endothelial, but lower in smooth muscle cells. Immunofluorescence staining showed that co-localization of ALOX12 and AIRE1 was more frequent in CD14(+)-monocytes than in CD4(+)-T cell in plaque than in non-plaque intima. CONCLUSIONS: Promoter methylation changes in AIRE1 and ALOX12 occur in atherosclerosis and can be considered as novel epigenetic markers.

Depressive Symptoms in Stroke Patients: Are There Sex Differences?

BACKGROUND: We aimed to examine sex differences in symptom characteristics and pharmacological responses in post-stroke depressive (PSD) symptoms. METHODS: This is a post hoc analysis of EMOTION (ClinicalTrials.gov, NCT01278498), a randomized, placebo-controlled, double-blind trial that examined the efficacy of escitalopram for 3 months on depression in patients with acute stroke. Depressive symptoms were evaluated using the 10-item Montgomery-Åsberg Depression Rating Scale (MADRS). Baseline characteristics, clinical variables, and treatment responses to escitalopram were compared between male and female patients. Treatment responses were defined as changes in MADRS (total score and its components) between baseline and 3 months and were compared between the escitalopram and placebo groups within each sex group. The least square mean was calculated to determine the independent effect of escitalopram, of which interaction was evaluated with patient sex. RESULTS: Of the 478 patients (intention-to-treat population), 187 (39%) were female. Female patients were significantly older than male patients and demonstrated more severe depressive symptoms at baseline (male vs. female, MADRS score, mean [SD]: 9.7 ± 8.0 vs. 12.2 ± 8.4, p = 0.001), especially in apparent sadness, reported sadness, and reduced appetite items. These differences were significant after adjustment for age and the severity of neurologic deficits. The female escitalopram group showed a significant 3-month improvement in MADRS scores (placebo [n = 86] vs. escitalopram [n = 101], least square mean [95% CI] -2.7 [-4.1 to -1.2] vs. -5.0 [-6.4 to -3.6], p = 0.007), and this efficacy was prominent in apparent sadness, reported sadness, and pessimistic thoughts items. However, there was no significant effect of escitalopram on depressive symptoms in the male group. The treatment responses of escitalopram tended to be more pronounced in the female group, particularly in alleviating a subset of depressive symptoms such as apparent sadness (p for interaction = 0.009). CONCLUSION: PSD may differ according to sex in its symptom characteristics and treatment responses to escitalopram, and tailored treatment strategies for PSD may therefore be needed.

Outcome Differences by Delirium Motor Subtype in Patients with Ischemic Stroke.

OBJECTIVE: This study evaluated the outcomes of ischemic stroke patients according to delirium motor subtype. METHODS: This study included patients who were admitted to the stroke unit between August 2017 and March 2019 and met the DSM-5 diagnostic criteria for delirium. Patients were assessed twice weekly throughout their delirium episodes using the Korean version of the Delirium Motor Subtype Scale (K-DMSS) and the Korean version of the Delirium Rating Scale-Revised-98 (K-DRS-98). The clinical characteristics and short-term outcomes of the patients were also assessed. RESULTS: A total of 943 stroke patients were included; the rate of incident delirium was 10.18%. Of the 95 delirium patients, 34 were classified as the hyperactive subtype, 30 as the mixed subtype, 25 as the hypoactive and six as no subtype. Among the subtype groups, the hypoactive subtype had the highest initial scores on the National Institutes of Health Stroke Scale (NIHSS; 6.72±4.75, p=0.02) and the modified Rankin Scale (mRS; 3.96±1.24, p<0.01). Additionally, the mixed and hypoactive subtypes had longer durations (p<0.01) and more severe symptoms of delirium (p=0.03) than the other motor subtypes, and the hypoactive subtype group had a significantly longer hospital stay (36.88±27.71 days, p<0.01) than the other subtype groups. After adjusting for baseline covariates in a multiple linear regression analysis, these differences remained significant. CONCLUSION: The present results suggest that the motor subtype of delirium is associated with different characteristics and outcomes in ischemic stroke patients.

Fabrication and Characterization of Bioresorbable Drug-coated Porous Scaffolds for Vascular Tissue Engineering.

Bioresorbable polymers have been studied for several decades as attractive candidates for promoting the advancement of medical science and bio-technology in modern society. In particular, with a well-defined architecture, bioresorbable polymers have prominent advantages over their bulk counterparts for applications in biomedical and implant devices, such as cell delivery, scaffolds for tissue engineering, and hydrogels as well as in the pharmaceutical fields. Biocompatible implant devices based on bioresorbable materials (for instance, bioresorbable polymers that combine the unique advantages of biocompability and easy handling) have emerged as a highly active field due to their promising applications in artificial implant systems and biomedical devices. In this paper, we report an approach to fabricate porous polycaprolactone (PCL) scaffolds using a 3D printing system. And its surface was treated to a hydrophilic surface using plasma treatment. Then, the aspirin and atorvastatin calcium salt mixture was dip coated onto the surface. The drug coating technology was used to deposit the drug material onto the scaffold surface. Our porous PCL scaffold was coated with aspirin and atorvastatin calcium salt to reduce the blood LDL cholesterol and restenosis. These results suggest that our approach may provide a promising scaffold for developing bioresorbable drug-delivery-biomaterials. We further demonstrate that our bioresorbable medical device can be used as vascular scaffolds to provide a wide range of applications for the design of medical devices.

Use of microcatheters for suction thrombectomy of acute distal occlusions.

We report our initial experience of using a microcatheter for contact aspiration of acute distal occlusions for recanalization. Endovascular technique and a case using Excelsior XT-27 microcatheter are presented. After manual suction within distal middle cerebral artery segments using a 50-ml syringe, instant and complete recanalization was obtained. Microcatheter suction thrombectomy using a 50-ml syringe can be considered a feasible treatment option for acute distal small artery occlusions.

Medication Adherence of Statin Users after Acute Ischemic Stroke.

Although statins are established therapy for the secondary prevention of ischemic stroke, factors associated with adherence to statin treatment following ischemic stroke are not well known. To address this, we assessed the 6-month statin adherence using 8-item Morisky Medication Adherence Scale-8 in patients with acute ischemic stroke. Of 991 patients, 65.6% were adherent to statin at 6-month after discharge. Multiple logistic regression analysis showed that patients' awareness of hyperlipidemia (OR 1.62; 95% CI 1.07-2.43), large artery stroke subtype (versus non-large artery stroke, OR 1.79; 95% CI 1.19-2.68), and alcohol drinking habits (OR 1.64; 95% CI 1.06-2.53) were positively associated, while high statin dose (versus low dose, OR 0.6; 95% CI 0.40-0.90) and higher daily number of medication pills (OR 0.93; 95% CI 0.88-0.97) were found to have a negative association with self-reported good adherence to statin medication after acute ischemic stroke. However, stroke severity and diagnosis of hyperlipidemia were not associated with adherence. These results suggest that educational and motivational interventions may enhance statin adherence because modifiable factors were associated with statin adherence.

Differences in Therapeutic Responses and Factors Affecting Post-Stroke Depression at a Later Stage According to Baseline Depression.

BACKGROUND AND PURPOSE: The pathophysiology of post-stroke depression (PSD) is complex and may differ according to an individual's mood immediately after stroke. Here, we compared the therapeutic response and clinical characteristics of PSD at a later stage between patients with and without depression immediately after stroke. METHODS: This study involved a post hoc analysis of data from EMOTION (ClinicalTrials.gov NCT01278498), a placebo-controlled, double-blind trial that examined the efficacy of escitalopram (10 mg/day) on PSD and other emotional disturbances among 478 patients with acute stroke. Participants were classified into the Baseline-Blue (patients with baseline depression at the time of randomization, defined per the Montgomery-Asberg Depression Rating Scale [MADRS] ≥8) or the Baseline-Pink groups (patients without baseline depression). We compared the efficacy of escitalopram and predictors of 3-month PSD (MADRS ≥8) between these groups. RESULTS: There were 203 Baseline-Pink and 275 Baseline-Blue patients. The efficacy of escitalopram in reducing PSD risk was more pronounced in the Baseline-Pink than in the Baseline-Blue group (p for interaction=0.058). Several risk factors differentially affected PSD development based on the presence of baseline depression (p for interaction <0.10). Cognitive dysfunction was an independent predictor of PSD in the Baseline-Blue, but not in the Baseline-Pink group, whereas the non-use of escitalopram and being female were more strongly associated with PSD in the Baseline-Pink group. CONCLUSIONS: Responses to escitalopram and predictors of PSD 3 months following stroke differed based on the presence of baseline depression. Our data suggest that PSD pathophysiology is heterogeneous; therefore, different therapeutic strategies may be needed to prevent PSD emergence following stroke.

High red blood cell composition in clots is associated with successful recanalization during intra-arterial thrombectomy.

We evaluated the composition of individual clots retrieved during intra-arterial thrombectomy in relation to recanalization success, stroke subtype, and the presence of clot signs on initial brain images. We analyzed clot and interventional data from 145 retrieval trials performed for 37 patients (69.5±14.0 years, 20 men, large artery atherosclerosis, n = 7; cardioembolism, n = 22; undetermined etiology, n = 8) who had undergone intra-arterial thrombectomy. Rates of clot retrieval and successful recanalization (Arterial Occlusive Lesion score of 2-3) for separate retrieval trials were evaluated. The area occupied by red blood cell (RBC), fibrin/platelets, and white blood cell (WBC) was measured from digitized images of hematoxylin-eosin stained clots. Compositional differences were compared according to recanalization success, stroke subtype, and the presence of hyperdense clot sign on initial computed tomography and/or blooming artifact on magnetic resonance image. Of the 145 total retrieval trials (3.4±2.4 times per patient), clot was retrieved in 93 trials (64%), while recanalization was successful in 73 (50%). Fibrin/platelets (63%) occupied the greatest area in retrieved clots, followed by RBCs (33%) and WBCs (4%). Clots retrieved from successful recanalization exhibited higher RBC composition (37%) than those retrieved from non-recanalization trials (20%, p = 0.001). RBC composition was higher in cardioembolic stroke (38%) rather than large artery atherosclerosis (23%) and undetermined etiology (26%, p = 0.01). Clots exhibiting clot signs (40%) had higher RBC composition than those without clot signs (19%, p = 0.001). RBC-rich clots were associated with successful recanalization of intra-arterial thrombectomy, cardioembolic stroke, and the presence of clot-signs on initial brain images.

The Effect of Inter-Departmental Stroke Meetings on Rehabilitation in a Comprehensive Cerebrovascular Center.

BACKGROUND: Stroke is the number one cause of adulthood disability in Korea. Rehabilitation after stroke can minimize functional disability, enhance recovery toward independence, and optimize community reintegration. The inter-departmental stroke meeting (IDSM) is a potential method to improve rehabilitation outcomes in patients with stroke. We aimed to analyze the effect of IDSM on rehabilitation after acute ischemic stroke management. METHODS: Medical records of 753 patients with acute ischemic stroke admitted to the neurology department of our medical center between January and December 2014 were reviewed retrospectively. In May 2014, weekly IDSMs were initiated. All physicians responsible for the patient's care reviewed patient treatment, methods of secondary prevention, and future rehabilitation plans. RESULTS: The transfer rate significantly increased after initiation of IDSM (phase 2, 3) and the length of stay (LOS) before transfer to the rehabilitation department decreased significantly from 9.68 ± 8.50 days to 5.75 ± 2.12 days. There was a reduction in the total LOS from 52 ± 28.57 days to 35 ± 27.21 days after IDSMs were introduced. In non-transferred patients also, the total LOS reduced significantly. The transfer rate increased significantly and the LOS before transfer to the rehabilitation department decreased significantly after implementation of IDSM in a subgroup of patients with moderate to severe stroke. CONCLUSION: The introduction of IDSM was significantly correlated with improvements in transfer rates and reduction of LOS in hospital. This finding shows that IDSMs are an important intervention to improve therapeutic progress and outcomes for patients with stroke.

Cryptogenic Stroke and High-Risk Patent Foramen Ovale: The DEFENSE-PFO Trial.

BACKGROUND: Recent reports showing the favorable role of patent foramen ovale (PFO) closure in patients with cryptogenic stroke have raised the issue of selecting optimal candidates. OBJECTIVES: This study, DEFENSE-PFO (Device Closure Versus Medical Therapy for Cryptogenic Stroke Patients With High-Risk Patent Foramen Ovale), evaluated whether the benefits of PFO closure can be determined on the basis of the morphologic characteristics of the PFO, as evaluated by transesophageal echocardiography. METHODS: Patients with cryptogenic stroke and high-risk PFO were divided between a transcatheter PFO closure and a medication-only group. High-risk PFO included PFO with atrial septal aneurysm, hypermobility (phasic septal excursion into either atrium ≥10 mm), or PFO size (maximum separation of the septum primum from the secundum) ≥2 mm. The primary endpoint was a composite of stroke, vascular death, or Thrombolysis In Myocardial Infarction-defined major bleeding during 2 years of follow-up. RESULTS: From September 2011 until October 2017, 120 patients (mean age: 51.8 years) underwent randomization. PFO size, frequency of septal aneurysm (13.3% vs. 8.3%; p = 0.56), and hypermobility (45.0% vs. 46.7%; p > 0.99) were similar between the groups. All PFO closures were successful. The primary endpoint occurred exclusively in the medication-only group (6 of 60 patients; 2-year event rate: 12.9% [log-rank p = 0.013]; 2-year rate of ischemic stroke: 10.5% [p = 0.023]). The events in the medication-only group included ischemic stroke (n = 5), cerebral hemorrhage (n = 1), Thrombolysis In Myocardial Infarction-defined major bleeding (n = 2), and transient ischemic attack (n = 1). Nonfatal procedural complications included development of atrial fibrillation (n = 2), pericardial effusion (n = 1), and pseudoaneurysm (n = 1). CONCLUSIONS: PFO closure in patients with high-risk PFO characteristics resulted in a lower rate of the primary endpoint as well as stroke recurrence. (Device Closure Versus Medical Therapy for Cryptogenic Stroke Patients With High-Risk Patent Foramen Ovale [DEFENSE-PFO]; NCT01550588).

Low Common Carotid Artery Systolic Occlusion Pressure and Symptomatic Carotid Artery Stenosis Are Associated with Development of Neurologic Intolerance during Proximal Protected Carotid Artery Stenting.

BACKGROUND AND OBJECTIVES: Neurologic intolerance (NI) is defined as the occurrence of neurological symptoms during carotid artery stenting (CAS). Because NI is inevitable problem, it may be helpful to anticipate its occurrence. So, we studied factors associated with NI during proximal protected CAS. METHODS: We retrospectively analyzed all consecutive patients underwent proximal protected CAS from August 2012 to January 2017. RESULTS: We included total 123 patients (109 males, 72±8 years old). The total procedure time was 43±12 minutes, and mean occlusion time was 4.8±1.2 minutes. We divided CAS patients into 2 groups according to presence of NI; neurologic tolerance (NT; n=74, 60%) and NI (n=49, 40%) groups. After the univariate analysis, symptomatic carotid artery stenosis (p=0.003), absence of anterior communicating artery (p=0.015) and low common carotid artery occlusion pressure (CCAOP, p<0.001) were associated with NI. After the multivariate analysis, NI was significantly associated with symptomatic carotid artery stenosis (odds ratio [OR], 5.549; p=0.014) and systolic CCAOP≤42 mmHg (OR, 6.461; p<0.001). In NI group, 43 patients (88%) recovered right after the balloon deflation and 2 patients were normalized within 2 hours. However, 1 had major stroke and 3 had minor strokes in 4 patients with persistent NI ≥24 hours. CONCLUSIONS: About 40% showed NI during the CAS. Most of them (88%, 43 of 49 patients) recovered after the balloon deflation, but stroke incidence was significantly higher in NI group. Symptomatic carotid artery stenosis and systolic CCAOP ≤42 mmHg were significantly associated with the development of NI during proximal protected CAS.

Low- versus Standard-Dose Intravenous Alteplase in the Context of Bridging Therapy for Acute Ischemic Stroke: A Korean ENCHANTED Study.

BACKGROUND AND PURPOSE: Following the positive results from recent trials on endovascular therapy (EVT), bridging therapy (intravenous alteplase plus EVT) is increasingly being used for the treatment of acute ischemic stroke. However, the optimal dose of intravenous alteplase remains unknown in centers where bridging therapy is actively performed. The optimal dose for eventual recanalization and positive clinical outcomes in patients receiving bridging therapy also remains unknown. METHODS: In this prospective Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) sub-study, we explored the outcomes following treatment with two different doses (low- [0.6 mg/kg] or standard-dose [0.9 mg/kg]) of intravenous alteplase across 12 Korean centers where EVT is actively performed. The primary endpoint was a favorable outcome at 90 days (modified Rankin Scale scores 0 to 1). Secondary endpoints included symptomatic intracerebral hemorrhage (ICH) in all patients, and the recanalization rate and favorable outcome in patients who underwent cerebral angiography for EVT (ClinicalTrials.gov, number NCT01422616). RESULTS: Of 351 patients, the primary outcome occurred in 46% of patients in both the standard-(80/173) and low-dose (81/178) groups (odds ratio [OR], 1.14; 95% confidence interval [CI], 0.72 to 1.81; P=0.582), although ICHs tended to occur more frequently in the standard-dose group (8% vs. 3%, P=0.056). Of the 67 patients who underwent cerebral angiography, there was no significant difference in favorable functional outcome between the standard- and low-dose groups (39% vs. 21%; OR, 2.39; 95% CI, 0.73 to 7.78; P=0.149). CONCLUSIONS: There was no difference in functional outcome between the patients receiving different doses of alteplase in centers actively performing bridging therapy.