A Comparison of Two LDL Cholesterol Targets after Ischemic Stroke.

BACKGROUND: The use of intensive lipid-lowering therapy by means of statin medications is recommended after transient ischemic attack (TIA) and ischemic stroke of atherosclerotic origin. The target level for low-density lipoprotein (LDL) cholesterol to reduce cardiovascular events after stroke has not been well studied. METHODS: In this parallel-group trial conducted in France and South Korea, we randomly assigned patients with ischemic stroke in the previous 3 months or a TIA within the previous 15 days to a target LDL cholesterol level of less than 70 mg per deciliter (1.8 mmol per liter) (lower-target group) or to a target range of 90 mg to 110 mg per deciliter (2.3 to 2.8 mmol per liter) (higher-target group). All the patients had evidence of cerebrovascular or coronary-artery atherosclerosis and received a statin, ezetimibe, or both. The composite primary end point of major cardiovascular events included ischemic stroke, myocardial infarction, new symptoms leading to urgent coronary or carotid revascularization, or death from cardiovascular causes. RESULTS: A total of 2860 patients were enrolled and followed for a median of 3.5 years; 1430 were assigned to each LDL cholesterol target group. The mean LDL cholesterol level at baseline was 135 mg per deciliter (3.5 mmol per liter), and the mean achieved LDL cholesterol level was 65 mg per deciliter (1.7 mmol per liter) in the lower-target group and 96 mg per deciliter (2.5 mmol per liter) in the higher-target group. The trial was stopped for administrative reasons after 277 of an anticipated 385 end-point events had occurred. The composite primary end point occurred in 121 patients (8.5%) in the lower-target group and in 156 (10.9%) in the higher-target group (adjusted hazard ratio, 0.78; 95% confidence interval, 0.61 to 0.98; P = 0.04). The incidence of intracranial hemorrhage and newly diagnosed diabetes did not differ significantly between the two groups. CONCLUSIONS: After an ischemic stroke or TIA with evidence of atherosclerosis, patients who had a target LDL cholesterol level of less than 70 mg per deciliter had a lower risk of subsequent cardiovascular events than those who had a target range of 90 mg to 110 mg per deciliter. (Funded by the French Ministry of Health and others; Treat Stroke to Target ClinicalTrials.gov number, NCT01252875.).

Safety and Efficacy of Otaplimastat in Patients with Acute Ischemic Stroke Requiring tPA (SAFE-TPA): A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Study.

OBJECTIVE: Otaplimastat is a neuroprotectant that inhibits matrix metalloprotease pathway, and reduces edema and intracerebral hemorrhage induced by recombinant tissue plasminogen activator (rtPA) in animal stroke models. We aimed to assess the safety and efficacy of otaplimastat in patients receiving rtPA. METHODS: This was a phase 2, 2-part, multicenter trial in stroke patients (19-80 years old) receiving rtPA. Intravenous otaplimastat was administered <30 minutes after rtPA. Stage 1 was a single-arm, open-label safety study in 11 patients. Otaplimastat 80 mg was administered twice daily for 3 days. Stage 2 was a randomized, double-blind, placebo-controlled study involving 69 patients, assigned (1:1:1) to otaplimastat 40 mg, otaplimastat 80 mg, or a placebo. The primary endpoint was the occurrence of parenchymal hematoma (PH) on day 1. Secondary endpoints included serious adverse events (SAEs), mortality, and modified Rankin scale (mRS) distribution at 90 days (clinicaltrials.gov identifier: NCT02787278). RESULTS: No safety issues were encountered in stage 1. The incidence of PH during stage 2 was comparable: 0 of 22 with the placebo, 0 of 22 with otaplimastat 40 mg, and 1 of 21 with the 80 mg dose. No differences in SAEs (13%, 17%, 14%) or death (8.3%, 4.2%, 4.8%) were observed among the 3 groups. Three adverse events (chills, muscle rigidity, hepatotoxicity) were judged to be related to otaplimastat. INTERPRETATION: Intravenous otaplimastat adjunctive therapy in patients receiving rtPA is feasible and generally safe. The functional efficacy of otaplimastat needs to be investigated with further large trials. ANN NEUROL 2020;87:233-245.

Clinical Implications of Basilar Artery Plaques in the Pontine Infarction with Normal Basilar Angiogram: A High-Resolution Magnetic Resonance Imaging Study.

BACKGROUND: Using high-resolution magnetic resonance imaging (HR-MRI), we investigated the impact of basilar artery plaques that were not detected by magnetic resonance angiography (MRA) on the functional outcomes of patients with acute pontine infarction. METHODS: A total of 40 patients with acute pontine infarction and normal basilar findings on MRA prospectively underwent HR-MRI for detection of basilar artery plaques. A relevant plaque was defined as one on the dorsal side of basilar artery, the same side of the ischemic lesion, and the same axial slices of the ischemic lesion. We analyzed the relationship between the relevant basilar artery plaques and the functional outcomes at 3 months. RESULTS: The initial National Institutes of Health Stroke Scale score (3.5 versus 2.0, P = .012), and the incidences of neurological deterioration (42.9% versus 6.3%, P = .031) and unfavorable functional outcome (71.4% versus 12.5%, P = .001) were higher in patients with relevant basilar artery plaques than in those without. On multiple regression analysis, the relevant basilar artery plaque was a significant and independent predictor of unfavorable functional outcome (odds ratio, 6.662; 95% confidence interval, 1.117-39.735; P = .037). CONCLUSIONS: The presence of a relevant basilar artery plaque was closely related with unfavorable functional outcome in patients with acute pontine infarction even if the patients' MRA showed normal basilar findings.

Neuroanatomical correlation of urinary retention in lateral medullary infarction.

We prospectively recruited 10 patients who presented with urinary retention as a neurological deficit that was attributable to lateral medullary infarction. Of these, 9 patients underwent a urodynamic study, which demonstrated detrusor underactivity of the bladder in 7 patients. Urinary retention developed mainly when the lesions involved the lateral tegmentum of the middle or caudal medulla. We concluded that interruption of the descending pathway from the pontine micturition center to the sacral spinal cord in the lateral medulla was responsible for the development of urinary retention.

Impact of thyroid autoantibodies on functional outcome in patients with acute ischemic stroke.

BACKGROUND: Recent studies have shown that thyroid autoantibodies contribute to the development of cerebrovascular diseases, including atherosclerosis, moyamoya disease, and even arterial dissection, induced by immune-mediated endothelial dysfunction on the cerebral vasculature. The aim of this study was to investigate the impact of thyroid autoantibodies on functional outcome in patients with acute ischemic stroke. METHODS: We reviewed the patients with acute ischemic stroke who consecutively underwent thyroid autoantibody tests. We divided the patients into positive thyroid autoantibody (PAB) and negative thyroid autoantibody (NAB) groups. Demographic profiles, risk factors, stroke subtypes, laboratory results, and functional outcomes were compared between the 2 groups. We performed the multivariate analysis to determine whether thyroid autoantibodies were independently associated with functional outcome. RESULTS: Of the 763 patients, 121 (15.9%) were of the PAB group. Compared with the NAB group, higher baseline National Institutes of Health Stroke Scale score (P = .001) and prevalence of large-artery atherosclerosis (P = .014) were found in the PAB group. The PAB group had significantly higher proportion of unfavorable outcome at 3 months (modified Rankin Scale score ≥ 3) than the NAB group (P = .002). On multiple regression analysis, lower tri-iodothyronine level (odds ratio [OR] .985, 95% confidence interval [CI] .976-.995, P = .002) and PABs (OR 1.661, 95% CI 1.013-2.724, P = .044) were significant and independent predictors of unfavorable outcome. CONCLUSIONS: This study showed that elevated thyroid autoantibodies were independently associated with unfavorable outcome in patients with acute ischemic stroke. We speculate that immune-mediated vascular damage may contribute to the increased risk of unfavorable outcome by providing insufficient cerebral blood flow to the ischemic area.

Additional rescue stenting with Neuroform Atlas stents during stent-assisted coiling of saccular aneurysms.

OBJECTIVE: Overlapping stenting is sometimes attempted during endovascular treatment of cerebral aneurysm as a rescue for coil herniation, stent mal-positioning, or in-stent thrombosis. We retrospectively evaluated the efficacy and safety of additional rescue stenting (ARS) in telescoping fashion with Neuroform Atlas stent (NAS) during stent-assisted coiling of saccular aneurysms. METHODS: We collected clinical and radiological data of patients with saccular aneurysms treated with ARS using NASs between March 2018 and December 2021. Y or X-stent-assisted coiling technique was excluded. RESULTS: Eighteen unruptured and 5 ruptured aneurysms in 23 patients were treated with ARS using NASs. Sizes of aneurysms ranged from 2.0 mm to 10.0 mm (mean: 5.0 mm). Immediate angiographic results were complete occlusion in 11 aneurysms, residual neck in 4 aneurysms, and residual sac in 8 aneurysms. Peri-operative morbidity was 4.3 %. Nineteen of 23 patients underwent follow-up conventional angiography (mean, 9.9 months). Results showed progressive occlusion in 10 (52.6 %) cases and asymptomatic in-stent stenosis in 3 (15.8 %) cases. At the end of the observation period (mean, 17.4 months), all 18 patients without subarachnoid hemorrhage had excellent clinical outcomes (mRS of 0), except one (mRS of 1). Of five patients with subarachnoid hemorrhage, four had a favorable outcome (mRS of 0-1), while the other one was dependent (mRS of 4). CONCLUSION: In this report on 23 patients, ARS with NASs for treating saccular aneurysms showed good technical safety with favorable clinical and angiographic outcomes. However, delayed in-stent stenosis was not uncommon. Thus, regular imaging follow-up is required.

Efficacy and safety of oxiracetam in patients with vascular cognitive impairment: A multicenter, randomized, double-blinded, placebo-controlled, phase IV clinical trial.

BACKGROUND: Oxiracetam may have a modest effect on preventing cognitive decline. Exercise can also enhance cognitive function. This trial aims to investigate the effect of oxiracetam on post-stroke cognitive impairment and explore whether this effect is modified by exercise. Furthermore, the mechanisms that mediate this effect will be investigated through a neural network analysis. METHODS: This is a multicenter, randomized, double-blind, placebo-controlled phase IV trial. Patients who complained of cognitive decline 3 months after stroke and had a high risk of cognitive decline were eligible. Patients were randomly assigned to receive either 800 mg of oxiracetam or placebo twice daily for 36 weeks. After randomization, a predetermined exercise protocol was provided to each participant, and the degree of physical activity was assessed using wrist actigraphy at 4, 12, 24, and 36 weeks. Resting-state functional MRI was obtained in baseline and 36-week follow-up. Co-primary endpoints are changes in the Mini-Mental State Examination and Clinical Dementia Rating-Sum of Boxes. Secondary endpoints include changes in the NINDS-CSN VCIHS-Neuropsychology Protocol, Euro QoL, patient's global assessment, and functional network connectivity. If there is a significant difference in physical activity between the two groups, the interaction effect between physical activity and the treatment group will be examined. A total of 500 patients were enrolled from February 2018, and the last patient's final follow-up was completed in September 2022. CONCLUSION: This trial is meaningful not only to prove the efficacy of oxiracetam, but also evaluate whether exercise can modify the effects of medication and how cognitive function can be restored. Trial registrationhttp://cris.nih.go.kr (KCT0005137).

Stacking ensemble learning model to predict 6-month mortality in ischemic stroke patients.

Patients with acute ischemic stroke can benefit from reperfusion therapy. Nevertheless, there are gray areas where initiation of reperfusion therapy is neither supported nor contraindicated by the current practice guidelines. In these situations, a prediction model for mortality can be beneficial in decision-making. This study aimed to develop a mortality prediction model for acute ischemic stroke patients not receiving reperfusion therapies using a stacking ensemble learning model. The model used an artificial neural network as an ensemble classifier. Seven base classifiers were K-nearest neighbors, support vector machine, extreme gradient boosting, random forest, naive Bayes, artificial neural network, and logistic regression algorithms. From the clinical data in the International Stroke Trial database, we selected a concise set of variables assessable at the presentation. The primary study outcome was all-cause mortality at 6 months. Our stacking ensemble model predicted 6-month mortality with acceptable performance in ischemic stroke patients not receiving reperfusion therapy. The area under the curve of receiver-operating characteristics, accuracy, sensitivity, and specificity of the stacking ensemble classifier on a put-aside validation set were 0.783 (95% confidence interval 0.758-0.808), 71.6% (69.3-74.2), 72.3% (69.2-76.4%), and 70.9% (68.9-74.3%), respectively.

Comparing carotid endarterectomy and carotid artery stenting: retrospective single-center analysis.

BACKGROUND: Extracranial cerebrovascular diseases represent approximately 20% of ischemic stroke cases. Carotid endarterectomy (CEA) was the gold standard procedure for carotid artery stenosis treatment until the introduction of carotid artery stenting (CAS) in the 1980s. While there have been several multicenter randomized trials comparing CEA and CAS, a more efficacious procedure has not been conclusively distinguished. This study reports the results of CAS versus CEA in patients with symptomatic or asymptomatic carotid stenosis and compares them with those from other studies. METHODS: This study is a single-center retrospective study and included patients who underwent CAS and CEA as elective surgery between January 2012 and December 2020. The final analysis included patient baseline characteristics, postoperative complications, and patient outcomes. RESULTS: The 235 patients included were assigned to the CAS (n=128) and CEA (n=107) groups. Within 30 days postoperatively, no significant differences were noted in myocardial infarction [n=1, 0.8% (CAS); n=1, 0.9% (CEA); P=0.899], cerebral infarction [n=4, 3.1% (CAS); n=1, 0.9% (CEA); P=0.247], and patient mortality [n=1, 0.8% (CAS); n=0, 0% (CEA); P=0.247]. CONCLUSIONS: In elective surgery, CAS and CEA had the same effect of preventing cerebral infarction with no difference in postoperative complications.

Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia: The Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia Study.

BACKGROUND AND PURPOSE: Blood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia. METHODS: This multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP [systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg]. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: NCT03231293). RESULTS: Of 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event. CONCLUSIONS: Fimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.

Prevalence of attention deficit hyperactivity disorder symptoms in narcolepsy: a systematic review.

OBJECTIVE: Narcolepsy is characterized by excessive daytime sleepiness and cataplexy. Attention deficit hyperactivity disorder (ADHD) is characterized by hyperactivity, inattention, and impulsivity. However, despite their differences, both narcolepsy and ADHD share the symptoms of sleep disturbance and excessive daytime sleepiness. Recent studies have suggested a link between the two disorders. The objective of systematic review was to assess the prevalence of ADHD symptoms in narcolepsy. METHODS: We performed a systematic search of MEDLINE (inception to December 2018) and EMBASE (inception to December 2018) for English publications of human studies using the keywords "narcolepsy" and "ADHD". RESULTS: Five studies examining a total of 328 patients met the eligibility criteria for this study examining the prevalence of ADHD symptoms in narcolepsy. The pooled prevalence of ADHD symptoms in narcolepsy was 33.0%. Two studies using the international classification of sleep disorders, second edition (ICSD-2) observed a pooled prevalence of ADHD symptoms in narcolepsy of 25.0%, while two other studies that relied on the ICSD-3 criteria observed a pooled prevalence of ADHD symptoms in narcolepsy of 36.4%. CONCLUSIONS: The prevalence of ADHD symptoms was >30%, making it an important comorbidity of narcolepsy. Future studies should be performed to better assess the relationship between ADHD and narcolepsy.

Prediction of early neurological deterioration in acute minor ischemic stroke by machine learning algorithms.

OBJECTIVES: A significant proportion of patients with acute minor stroke have unfavorable functional outcome due to early neurological deterioration (END). The purpose of this study was to evaluate the applicability of machine learning algorithms to predict END in patients with acute minor stroke. PATIENTS AND METHODS: We collected clinical and neuroimaging information from patients with acute minor stroke with NIHSS score of ≤ 3. Early neurological deterioration was defined as any worsening of NIHSS score within 3 days after admission. Unfavorable functional outcome was defined as a modified Rankin Scale score of ≥ 2. We also compared clinical and neuroimaging information between patients with and without END. Four machine learning algorithms, i.e., Boosted trees, Bootstrap decision forest, Deep neural network, and Logistic Regression, were selected and trained by our dataset to predict early neurological deterioration RESULTS: A total of 739 patients were included in this study. 78 patients (10.6%) experienced END. Among 78 patients with END, 61 (78.2%) had unfavorable functional outcome at 90 days after stroke onset. On multivariate analysis, the initial NIHSS score (P = 0.003), hemorrhagic transformation (P = 0.010), and stenosis (P = 0.014) or occlusion (P = 0.004) of a relevant artery were independently associated with END. Of the four machine learning algorithms, Boosted trees, Deep neural network, and Logistic Regression can be used to predict END in patients with acute minor stroke (Boosted trees: accuracy = 0.966, F1 score = 0.8 and area under the curve = 0.934, Deep neural network :0.966, 0.8, and 0. 904, and Logistic Regression : 0.966, 0.8, and 0.885). CONCLUSIONS: This study suggests that machine learning algorithms that integrate clinical and neuroimaging information can be used to predict END in patients with acute minor stroke. Further studies based on larger, multicenter datasets are needed to predict END accurately for designing treatment strategies and obtaining favorable functional outcome.

Endovascular treatment of the vertebral artery origin stenosis by using the closed-cell, self-expandable Carotid Wallstent.

BACKGROUND: Endovascular treatment has been considered a good alternative to surgery for symptomatic vertebral artery origin stenosis (VAOS) due to the high risk of morbidity associated with surgery. The purpose of this study was to evaluate the feasibility and efficacy of insertion of the closed-cell, self-expandable Carotid Wallstent for the treatment of VAOS. METHODS: The records of 72 patients with VAOS refractory to adequate medication who were treated by endovascular treatment with the Carotid Wallstent from December 2006 to November 2018 were retrospectively evaluated. RESULTS: Of the 72 patients, 43 presented with transient ischemic attacks. Forty-seven patients (65.3%) manifested other brachiocephalic stenoses; of these, 40 patients had occlusion, hypoplasia, or stenosis of the contralateral vertebral artery. Overall technical success (defined as 20% or less residual stenosis) was 100%. Procedure-related complications (n = 8, 11.1%) included sudden asystole (n = 1), acute in-stent thrombosis (n = 3), minor stroke (n = 3), and stent shortening (n = 1). All complications were resolved without permanent neurological deficit. Angiographic follow-up (mean, 13.0 months) was achieved in 49 patients and revealed in-stent restenosis in 1 patient (2.0%) and stent malposition by shortening in 2 patients (4.1%). Follow-up records were available in 57 patients (mean 15.6 months). Three of the 57 patients (n = 3, 5.3%) had recurrent symptoms of vertebrobasilar ischemia and none was retreated. CONCLUSIONS: Endovascular treatment of symptomatic VAOS using the closed-cell, self-expandable Carotid Wallstent is technically feasible and effective in alleviating patient symptoms and for improving vertebrobasilar blood flow.

Effects of dabigatran and rivaroxaban on stroke severity according to the results of routine coagulation tests.

INTRODUCTION: Prior use of direct oral anticoagulants has been associated with reduced stroke severity in patients with non-valvular atrial fibrillation (NVAF). The aim of this study was to investigate the impact of prothrombin time (PT) and activated partial thromboplastin time (aPTT) on stroke severity in patients who were receiving dabigatran or rivaroxaban at the time of stroke onset. MATERIALS AND METHODS: We enrolled 107 patients with NVAF who developed acute ischemic stroke while on dabigatran or rivaroxaban and presented within 24 hours to nine hospitals between January 2014 and December 2018. The results of PT and aPTT assays were obtained within 24 hours of stroke onset in all patients. We analyzed PT and aPTT in relation to stroke severity and ischemic lesion volume using correlation and multivariable regression analyses. RESULTS: Of the 107 patients included, 46 (43.0%) were on dabigatran and 61 (57.0%) were on rivaroxaban. In patients with prior dabigatran use, while aPTT was inversely correlated with admission National Institutes of Health Stroke Scale (NIHSS) score (r = -0.369, p = 0.012) and ischemic lesion volume (r = -0.480, p = 0.005), there was no correlation between PT and either of these variables. Multivariable analysis confirmed the existence of a significant independent inverse relationship between aPTT and NIHSS score at admission (B, -0.201; 95% confidence interval [CI], -0.370 to -0.032; p = 0.005) and between aPTT and ischemic lesion volume (B, -0.076; 95% CI, -0.130 to -0.023; p = 0.007). In patients with prior rivaroxaban use, neither PT nor aPTT was associated with admission NIHSS score or ischemic lesion volume in the correlation and multivariable analyses. CONCLUSIONS: In patients with NVAF who were receiving dabigatran, prolonged aPTT was associated with reduced stroke severity.

Outcomes of Carotid Endarterectomy according to the Anesthetic Method: General versus Regional Anesthesia.

BACKGROUND: The surgical strategies for carotid endarterectomy (CEA) vary in terms of the anesthesia method, neurological monitoring, shunt usage, and closure technique, and no gold-standard procedure has been established yet. We aimed to analyze the feasibility and benefits of CEA under regional anesthesia (RA) and CEA under general anesthesia (GA). METHODS: Between June 2012 and December 2017, 65 patients who had undergone CEA were enrolled, and their medical records were prospectively collected and retrospectively reviewed. A total of 35 patients underwent CEA under RA with cervical plexus block, whereas 30 patients underwent CEA under GA. In the RA group, a carotid shunt was selectively used for patients who exhibited negative results on the awake test. In contrast, such a shunt was used for all patients in the GA group. RESULTS: There were no cases of postoperative stroke, cardiovascular events, or mortality. Nerve injuries were noted in 4 patients (3 in the RA group and 1 in the GA group), but they fully recovered prior to discharge. Operative time and clamp time were shorter in the RA group than in the GA group (119.29±27.71 min vs. 161.43±20.79 min, p<0.001; 30.57±6.80 min vs. 51.77±13.38 min, p<0.001, respectively). The hospital stay was shorter in the RA group than in the GA group (14.6±5.05 days vs. 18.97±8.92 days, p=0.022). None of the patients experienced a stroke or restenosis during the 27.23±20.3-month follow-up period. CONCLUSION: RA with a reliable awake test reduces shunt use and decreases the clamp and operative times of CEA, eventually resulting in a reduced length of hospital stay.

Comparison of Clopidogrel and Ticlopidine/Ginkgo Biloba in Patients With Clopidogrel Resistance and Carotid Stenting.

Background and Purpose: Patients undergoing carotid artery stenting (CAS) who show low responsiveness to clopidogrel may have a higher risk of peri-procedural embolic events. This study aimed to compare the effectiveness and safety of clopidogrel and ticlopidine plus Ginkgo biloba in clopidogrel-resistant patients undergoing CAS. Methods: In this multi-center, randomized, controlled trial, we used platelet reactivity test to select patients undergoing CAS who showed clopidogrel resistance, and compared treatments using clopidogrel and ticlopidine plus ginkgo. The primary outcome was the incidence of new ischemic lesion in the ipsilateral hemisphere of CAS. Detection of microembolic signal on transcranial Doppler was the secondary outcome. The clinical outcomes were also monitored. Results: This trial was discontinued after 42 patients were randomized after preplanned interim sample size re-estimation indicated an impractical sample size. The primary endpoint occurred in 12/22 patients (54.5%) in the clopidogrel group and 13/20 patients (65.0%) in the ticlopidine-ginkgo group (P = 0.610). No significant differences in the presence of microembolic signal (15.0 vs. 11.8%, P = 0.580), clinical outcomes (ischemic stroke or transient ischemic attack, 0.0 vs. 5.5%; acute myocardial infarction 0.0 vs. 0.0%; all-cause death, 4.5 vs. 0.0%), or incidence of adverse events were found in the two groups. In terms of resistance to clopidogrel, treatment with ticlopidine-ginkgo significantly increased the P2Y12 Reaction Units (difference, 0.0 [-0.3-3.0] vs. 21.0 [6.0-35.0], P < 0.001). Conclusions: In patients who showed clopidogrel resistance, ticlopidine-ginkgo treatment was safe and increased P2Y12 Reaction Units; however, compared to clopidogrel, it failed to improve surrogate and clinical endpoints in patients undergoing CAS. This multimodal biomarker-based clinical trial is feasible in neurointerventional research. Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT02133989.

Feedback on Physical Activity Through a Wearable Device Connected to a Mobile Phone App in Patients With Metabolic Syndrome: Pilot Study.

BACKGROUND: Little is known of the effect of wearable devices on metabolic impairments in clinical settings. We hypothesized that a wearable device that can monitor and provide feedback on physical activity may help resolve metabolic syndrome. OBJECTIVE: This study aimed to examine the objective effects of the use of these devices on metabolic syndrome resolution. METHODS: Patients diagnosed with metabolic syndrome were recruited. Participants were prescribed regular walking using a wearable device (Coffee WALKIE +Dv.3, GC Healthcare CI, Korea) on their wrist for 12 weeks. Participants received self-feedback on the amount of their exercise through an app on their mobile phone. The information on physical activities of the participants was uploaded automatically to a website. Thus, a trained nurse could provide individuals with feedback regarding the physical activity via telephone consultation on alternate weeks. Blood pressure (BP), body composition, fasting plasma glucose, and lipid profiles were recorded. The primary outcome was metabolic syndrome resolution. The secondary outcome was an improvement in the components of metabolic impairment. RESULTS: Of the 53 participants recruited, 20 participants with a median age of 46 (range 36-50) years completed the trial. There was no significant difference in the amount of calorie expenditure at weeks 4, 8, and 12. After 12 weeks, metabolic syndrome was resolved in 9 of 20 participants (45%), and the mean number of metabolic impairment components per person decreased from 3.4 to 2.9. Particularly, the mean systolic and diastolic BP decreased from mean 136.6 (SD 18.5) mm Hg to mean 127.4 (SD 19.5) mm Hg and from mean 84.0 (SD 8.1) mm Hg to mean 77.4 (SD 14.4) mm Hg (both P=.02), respectively. CONCLUSIONS: This study found that a 12-week intervention via feedback, based on a wearable physical activity monitor, helped metabolic syndrome patients to be more engaged in regular walking and it improved impaired metabolic components, especially in BP. However, some practical challenges regarding patients' adherence and sustained engagement were observed.

Therapeutic-induced hypertension in patients with noncardioembolic acute stroke.

OBJECTIVE: To evaluate the safety and efficacy of induced hypertension in patients with acute ischemic stroke. METHODS: In this multicenter randomized clinical trial, patients with acute noncardioembolic ischemic stroke within 24 hours of onset who were ineligible for revascularization therapy and those with progressive stroke during hospitalization were randomly assigned (1:1) to the control and intervention groups. In the intervention group, phenylephrine was administered intravenously to increase systolic blood pressure (SBP) up to 200 mm Hg. The primary efficacy endpoint was early neurologic improvement (reduction in NIH Stroke Scale [NIHSS] score of ≥2 points during the first 7 days). The secondary efficacy endpoint was a modified Rankin Scale score of 0 to 2 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage/edema, myocardial infarction, and death. RESULTS: In the modified intention-to-treat analyses, 76 and 77 patients were included in the intervention and control groups, respectively. After adjustment for age and initial stroke severity, induced hypertension increased the occurrence of the primary (odds ratio 2.49, 95% confidence interval [CI] 1.25-4.96, p = 0.010) and secondary (odds ratio 2.97, 95% CI 1.32-6.68, p = 0.009) efficacy endpoints. Sixty-seven (88.2%) patients of the intervention group exhibited improvements in NIHSS scores of ≥2 points during induced hypertension (mean SBP 179·7 ± 19.1 mm Hg). Safety outcomes did not significantly differ between groups. CONCLUSION: Among patients with noncardioembolic stroke who were ineligible for revascularization therapy and those with progressive stroke, phenylephrine-induced hypertension was safe and resulted in early neurologic improvement and long-term functional independence. CLINICALTRIALSGOV IDENTIFIER: NCT01600235. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with acute ischemic stroke, therapeutic-induced hypertension increases the probability of early neurologic improvement.

Prediction of hemorrhagic transformation in patients with mild atrial fibrillation-associated stroke treated with early anticoagulation: post hoc analysis of the Triple AXEL Trial.

OBJECTIVES: To investigate the predictors of hemorrhagic transformation (HT) in patients with mild atrial fibrillation-related stroke who were treated with early anticoagulation. We conducted a post-hoc subgroup analysis from Acute Cerebral Infarction Patients with Non-valvular Atrial Fibrillation (Triple AXEL) study. PATIENTS AND METHODS: The Triple AXEL study was a randomized, multicenter, open-label, blinded end-point evaluation, comparative phase 2 trial. To identify the relationship between the type of HT and risk factors. We analyzed various factors using data from the Triple AXEL study, such as sex, history of hypertension, diabetes, microbleeds, concomitant antiplatelet use, initial infarction volume, initial infarction location, and new intracranial hemorrhage on follow-up gradient recalled echo or susceptibility-weighted imaging. RESULTS: We analyzed various factors by dividing patients into a new HT group and a no HT group. No correlation was found between HT and risk factors that were significantly associated with HT, including age, sex, history of hypertension, diabetes, microbleeds, concomitant antiplatelet use, and initial infarction volume. When the initial infarction was classified into anterior circulation infarction (ACI) and posterior circulation infarction (PCI), the occurrence of new HT was significantly more associated with PCI than with ACI (57.6% vs 24.0%, P = 0.001). Multivariate logistic regression analysis was performed using HT as a response variable. Only the location of initial infarction according to the vascular territory contributed to the increased risk of HT (OR2.3, 95%CI1.33-3.91, P = 0.003). CONCLUSION: PCI is a very important independent risk factor for HT in patients with mild AF-related stroke treated with early anticoagulation.