Publications by authors named "Yasushi Okada"

287 Publications

The function of Scox in glial cells is essential for locomotive ability in Drosophila.

Sci Rep 2021 Oct 27;11(1):21207. Epub 2021 Oct 27.

Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto, 606-8585, Japan.

Synthesis of cytochrome c oxidase (Scox) is a Drosophila homolog of human SCO2 encoding a metallochaperone that transports copper to cytochrome c, and is an essential protein for the assembly of cytochrome c oxidase in the mitochondrial respiratory chain complex. SCO2 is highly conserved in a wide variety of species across prokaryotes and eukaryotes, and mutations in SCO2 are known to cause mitochondrial diseases such as fatal infantile cardioencephalomyopathy, Leigh syndrome, and Charcot-Marie-Tooth disease, a neurodegenerative disorder. These diseases have a common symptom of locomotive dysfunction. However, the mechanisms of their pathogenesis remain unknown, and no fundamental medications or therapies have been established for these diseases. In this study, we demonstrated that the glial cell-specific knockdown of Scox perturbs the mitochondrial morphology and function, and locomotive behavior in Drosophila. In addition, the morphology and function of synapses were impaired in the glial cell-specific Scox knockdown. Furthermore, Scox knockdown in ensheathing glia, one type of glial cell in Drosophila, resulted in larval and adult locomotive dysfunction. This study suggests that the impairment of Scox in glial cells in the Drosophila CNS mimics the pathological phenotypes observed by mutations in the SCO2 gene in humans.
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http://dx.doi.org/10.1038/s41598-021-00663-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551190PMC
October 2021

Dual Antiplatelet Therapy Using Cilostazol in Patients With Stroke and Intracranial Arterial Stenosis.

J Am Heart Assoc 2021 10 8;10(20):e022575. Epub 2021 Oct 8.

National Cerebral and Cardiovascular Center Osaka Japan.

Background Long-term benefit of dual antiplatelet therapy (DAPT) over single antiplatelet therapy (SAPT) for the prevention of recurrent stroke has not been established in patients with intracranial arterial stenosis. We compared the efficacy and safety of DAPT with cilostazol and clopidogrel or aspirin to those of SAPT with clopidogrel or aspirin in patients with intracranial arterial stenosis, who were recruited to the Cilostazol Stroke Prevention Study for Antiplatelet Combination trial, a randomized controlled trial in high-risk Japanese patients with ischemic stroke. Methods and Results We compared the vascular and hemorrhagic events between DAPT and SAPT in patients with ischemic stroke and symptomatic or asymptomatic intracranial arterial stenosis of at least 50% in a major intracranial artery. Patients were placed in two groups: 275 were assigned to receive DAPT and 272 patients SAPT. The risks of ischemic stroke (hazard ratio [HR], 0.47; 95% CI, 0.23-0.95); and composite of stroke, myocardial infarction, and vascular death (HR, 0.48; 95% CI, 0.26-0.91) were lower in DAPT than SAPT, whereas the risk of severe or life-threatening bleeding (HR, 0.72; 95% CI, 0.12-4.30) did not differ between the 2 treatment groups. Conclusions DAPT using cilostazol was superior to SAPT with clopidogrel or aspirin for the prevention of recurrent stroke and vascular events without increasing bleeding risk among patients with intracranial arterial stenosis after stroke. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01995370.
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http://dx.doi.org/10.1161/JAHA.121.022575DOI Listing
October 2021

Intraplaque high-intensity signal on time-of-flight magnetic resonance angiography and restenosis after carotid artery stenting.

J Neurosurg 2021 Sep 24:1-6. Epub 2021 Sep 24.

1Department of Neuroendovascular Surgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center.

Objective: To test the hypothesis that intraplaque hemorrhage is a predictor of restenosis after carotid artery stenting (CAS), the association between intraplaque high-intensity signal (HIS) on time-of-flight MR angiography (TOF-MRA), as a marker of intraplaque hemorrhage, and restenosis after CAS was assessed in the present observational study.

Methods: Consecutive patients who underwent initial CAS for atherosclerotic stenosis in the cervical internal carotid artery in the authors' department were enrolled. Of these, patients without preprocedural cervical TOF-MRA were excluded. Outcome measures were ≥ 50% restenosis, defined as a peak systolic velocity of > 1.3 m/sec; or occlusion and ≥ 70% restenosis, defined as a peak systolic velocity of > 2.1 m/sec; or occlusion on carotid duplex ultrasound.

Results: Of 230 consecutive patients who underwent initial CAS, 22 without preprocedural cervical TOF-MRA were excluded. Of the remaining 208 patients (mean age 73 years; 33 women), 46 had intraplaque HIS. Ultrasound follow-up was not performed in 4 patients. The median follow-up duration was 3.2 years (interquartile range 1.7-5.1 years). During the follow-up period, 102 patients had ≥ 50% restenosis and 36 had ≥ 70% restenosis. Intraplaque HIS was significantly associated with increased risk of ≥ 50% restenosis (adjusted hazard ratio 2.18; 95% CI 1.28-3.68) and ≥ 70% restenosis (adjusted hazard ratio 3.12; 95% CI 1.32-7.52).

Conclusions: Intraplaque HIS on TOF-MRA was associated with increased risk of restenosis after CAS. The present results indicate that intraplaque hemorrhage is a predictor of restenosis after CAS.
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http://dx.doi.org/10.3171/2021.4.JNS21546DOI Listing
September 2021

Intensive blood pressure lowering with nicardipine and outcomes after intracerebral hemorrhage: An individual participant data systematic review.

Int J Stroke 2021 Sep 20:17474930211044635. Epub 2021 Sep 20.

Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.

Background And Aims: Nicardipine has strong, rapidly acting antihypertensive activity. The effects of acute systolic blood pressure levels achieved with intravenous nicardipine after onset of intracerebral hemorrhage on clinical outcomes were determined.

Methods: A systematic review and individual participant data analysis of articles before 1 October 2020 identified on PubMed were performed (PROSPERO: CRD42020213857). Prospective studies involving hyperacute intracerebral hemorrhage adults treated with intravenous nicardipine whose outcome was assessed using the modified Rankin Scale were eligible. Outcomes included death or disability at 90 days, defined as the modified Rankin Scale score of 4-6, and hematoma expansion, defined as an increase ≥6 mL from baseline to 24-h computed tomography.

Summary Of Review: Three studies met the eligibility criteria. For 1265 patients enrolled (age 62.6 ± 13.0 years, 484 women), death or disability occurred in 38.2% and hematoma expansion occurred in 17.4%. Mean hourly systolic blood pressure during the initial 24 h was positively associated with death or disability (adjusted odds ratio (aOR) 1.12, 95% confidence interval (CI) 1.00-1.26 per 10 mmHg) and hematoma expansion (1.16, 1.02-1.32). Mean hourly systolic blood pressure from 1 h to any timepoint during the initial 24 h was positively associated with death or disability. Later achievement of systolic blood pressure to ≤140 mmHg increased the risk of death or disability (aOR 1.02, 95% CI 1.00-1.05 per hour).

Conclusions: Rapid lowering of systolic blood pressure by continuous administration of intravenous nicardipine during the initial 24 h in hyperacute intracerebral hemorrhage was associated with lower risks of hematoma expansion and 90-day death or disability without increasing serious adverse events.
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http://dx.doi.org/10.1177/17474930211044635DOI Listing
September 2021

Effect of the Sodium-Glucose Cotransporter 2 Inhibitor Canagliflozin for Heart Failure With Preserved Ejection Fraction in Patients With Type 2 Diabetes.

Circ Rep 2021 Aug 22;3(8):440-448. Epub 2021 Jul 22.

Cardiovascular Medicine, Nara Medical University Kashihara Japan.

The efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors in elderly patients with heart failure with preserved ejection fraction (HFpEF) remains unclear. In a multicenter, controlled trial, the CANONICAL study, we enrolled 82 HFpEF (left ventricular ejection fraction [LVEF] ≥50%) patients with type 2 diabetes (T2D) aged ≥65 years, with plasma B-type natriuretic peptide (BNP) ≥100 pg/mL or plasma N-terminal pro BNP (NT-proBNP) ≥400 pg/mL or history of HF. Patients were randomly assigned to 2 groups and were administered either the SGLT2 inhibitor canagliflozin (100 mg/day) for 24 weeks or standard therapy. The primary endpoints were changes in body weight (BW) and BNP concentrations. Mean (±SD) patient age, body mass index, and LVEF were 75.7±6.5 years, 25.0±3.6 kg/m and 61.5±7.6%, respectively. At 24 weeks, BW was significantly lower in the canagliflozin than standard therapy group. The extent of BNP reductions at 4 weeks was significantly greater in the canagliflozin than standard therapy group (P<0.05), but at 24 weeks there was no significant difference between the 2 groups. In this study, canagliflozin treatment reduced BW, but did not significantly reduce plasma BNP concentrations compared with standard therapy after 24 weeks treatment in T2D patients with HFpEF. Further large-scale randomized studies are needed to conclude the beneficial effects of canagliflozin in T2D patients with HFpEF.
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http://dx.doi.org/10.1253/circrep.CR-21-0030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8338435PMC
August 2021

Suppression of Vps13 adaptor protein mutants reveals a central role for PI4P in regulating prospore membrane extension.

PLoS Genet 2021 08 18;17(8):e1009727. Epub 2021 Aug 18.

Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.

Vps13 family proteins are proposed to function in bulk lipid transfer between membranes, but little is known about their regulation. During sporulation of Saccharomyces cerevisiae, Vps13 localizes to the prospore membrane (PSM) via the Spo71-Spo73 adaptor complex. We previously reported that loss of any of these proteins causes PSM extension and subsequent sporulation defects, yet their precise function remains unclear. Here, we performed a genetic screen and identified genes coding for a fragment of phosphatidylinositol (PI) 4-kinase catalytic subunit and PI 4-kinase noncatalytic subunit as multicopy suppressors of spo73Δ. Further genetic and cytological analyses revealed that lowering PI4P levels in the PSM rescues the spo73Δ defects. Furthermore, overexpression of VPS13 and lowering PI4P levels synergistically rescued the defect of a spo71Δ spo73Δ double mutant, suggesting that PI4P might regulate Vps13 function. In addition, we show that an N-terminal fragment of Vps13 has affinity for the endoplasmic reticulum (ER), and ER-plasma membrane (PM) tethers localize along the PSM in a manner dependent on Vps13 and the adaptor complex. These observations suggest that Vps13 and the adaptor complex recruit ER-PM tethers to ER-PSM contact sites. Our analysis revealed that involvement of a phosphoinositide, PI4P, in regulation of Vps13, and also suggest that distinct contact site proteins function cooperatively to promote de novo membrane formation.
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http://dx.doi.org/10.1371/journal.pgen.1009727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372973PMC
August 2021

Cerebral microbleeds development after stroke thrombolysis: A secondary analysis of the THAWS randomized clinical trial.

Int J Stroke 2021 Aug 3:17474930211035023. Epub 2021 Aug 3.

Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.

Background And Aim: We determined to investigate the incidence and clinical impact of new cerebral microbleeds after intravenous thrombolysis in patients with acute stroke.

Methods: The THAWS was a multicenter, randomized trial to study the efficacy and safety of intravenous thrombolysis with alteplase in patients with wake-up stroke or unknown onset stroke. Prescheduled T2*-weighted imaging assessed cerebral microbleeds at three time points: baseline, 22-36 h, and 7-14 days. Outcomes included new cerebral microbleeds development, modified Rankin Scale (mRS) ≥3 at 90 days, and change in the National Institutes of Health Stroke Scale (NIHSS) score from 24 h to 7 days.

Results: Of all 131 patients randomized in the THAWS trial, 113 patients (mean 74.3 ± 12.6 years, 50 female, 62 allocated to intravenous thrombolysis) were available for analysis. Overall, 46 (41%) had baseline cerebral microbleeds (15 strictly lobar cerebral microbleeds, 14 mixed cerebral microbleeds, and 17 deep cerebral microbleeds). New cerebral microbleeds only emerged in the intravenous thrombolysis group (seven patients, 11%) within a median of 28.3 h, and did not additionally increase within a median of 7.35 days. In adjusted models, number of cerebral microbleeds (relative risk (RR) 1.30, 95% confidence interval (CI): 1.17-1.44), mixed distribution (RR 19.2, 95% CI: 3.94-93.7), and cerebral microbleeds burden ≥5 (RR 44.9, 95% CI: 5.78-349.8) were associated with new cerebral microbleeds. New cerebral microbleeds were associated with an increase in NIHSS score ( = 0.023). Treatment with alteplase in patients with baseline ≥5 cerebral microbleeds resulted in a numerical shift toward worse outcomes on ordinal mRS (median [IQR]; 4 [3-4] vs. 0 [0-3]), compared with those with <5 cerebral microbleeds (common odds ratio 17.1, 95% CI: 0.76-382.8). The association of baseline ≥5 cerebral microbleeds with ordinal mRS score differed according to the treatment group ( interaction = 0.042).

Conclusion: New cerebral microbleeds developed within 36 h in 11% of the patients after intravenous thrombolysis, and they were significantly associated with mixed-distribution and ≥5 cerebral microbleeds. New cerebral microbleeds development might impede neurological improvement. Furthermore, cerebral microbleeds burden might affect the effect of alteplase.
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http://dx.doi.org/10.1177/17474930211035023DOI Listing
August 2021

Right entorhinal cortical thickness is associated with Mini-Mental State Examination scores from multi-country datasets using MRI.

Neuroradiology 2021 Jul 11. Epub 2021 Jul 11.

Department of Radiology, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, 810-0065, Fukuoka, Japan.

Purpose: To discover common biomarkers correlating with the Mini-Mental State Examination (MMSE) scores from multi-country MRI datasets.

Methods: The first dataset comprised 112 subjects (49 men, 63 women; range, 46-94 years) at the National Hospital Organization Kyushu Medical Center. A second dataset comprised 300 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (177 men, 123 women; range, 57-91 years). Three-dimensional T1-weighted MR images were collected from both datasets. In total, 14 deep gray matter volumes and 70 cortical thicknesses were obtained from MR images using FreeSurfer software. Total hippocampal volume and the ratio of hippocampus to cerebral volume were also calculated. Correlations between each variable and MMSE scores were assessed using Pearson's correlation coefficient. Parameters with moderate correlation coefficients (r > 0.3) from each dataset were determined as independent variables and evaluated using general linear model (GLM) analyses.

Results: In Pearson's correlation coefficient, total and bilateral hippocampal volumes, right amygdala volume, and right entorhinal cortex (ERC) thickness showed moderate correlation coefficients (r > 0.3) with MMSE scores from the first dataset. The ADNI dataset showed moderate correlations with MMSE scores in more variables, including bilateral ERC thickness and hippocampal volume. GLM analysis revealed that right ERC thickness correlated significantly with MMSE score in both datasets. Cortical thicknesses of the left parahippocampal gyrus, left inferior parietal lobe, and right fusiform gyrus also significantly correlated with MMSE score in the ADNI dataset (p < 0.05).

Conclusion: A positive correlation between right ERC thickness and MMSE score was identified from multi-country datasets.
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http://dx.doi.org/10.1007/s00234-021-02767-yDOI Listing
July 2021

Time-outcome relationship in acute large-vessel occlusion exists across all ages: subanalysis of RESCUE-Japan Registry 2.

Sci Rep 2021 06 17;11(1):12782. Epub 2021 Jun 17.

Department of Clinical Epidemiology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.

Early reperfusion after endovascular thrombectomy is associated with an improved outcome in ischemic stroke patients; however, the time dependency in elderly patients remains unclear. We investigated the time-outcome relationships in different age subgroups. Of 2420 patients enrolled in the RESCUE-Japan Registry 2 study, a study based on a prospective registry of stroke patients with acute cerebral large-vessel occlusion at 46 centers, we analyzed the data of 1010 patients with successful reperfusion after endovascular therapy (mTICI of 2b or 3). In 3 age subgroups (< 70, 70 to < 80, and ≥ 80 years), the mRS scores at 90 days were analyzed according to 4 categories of onset-to-reperfusion time (< 180, 180 to < 240, 240 to < 300, and ≥ 300 min). In each age subgroup, the distributions of mRS scores were better with shorter onset-to-reperfusion times. The adjusted common odds ratios for better outcomes per 1-category delay in onset-to-reperfusion time were 0.66 (95% CI 0.55-0.80) in ages < 70 years, 0.66 (95% CI 0.56-0.79) in ages 70 to < 80 years, and 0.83 (95% CI 0.70-0.98) in ages ≥ 80 years. Early reperfusion was associated with better outcomes across all age subgroups. Achieving early successful reperfusion is important even in elderly patients.
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http://dx.doi.org/10.1038/s41598-021-92100-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211644PMC
June 2021

Microbleeds and clinical outcome in acute mild stroke patients treated with antiplatelet therapy: ADS post-hoc analysis.

J Clin Neurosci 2021 Jul 12;89:216-222. Epub 2021 May 12.

Department of Neurology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan; Department of Stroke Medicine, Kawasaki Medical School, Kurashiki, Japan.

Background And Purpose: In this post-hoc analysis using acute dual study dataset, the impacts of cerebral microbleeds (MBs) after mild stroke on clinical outcome were investigated.

Methods: The number of MBs on admission was categorized as 1) no MBs, 2) MBs 1-4, 3) MBs 5-9, and 4) MBs ≥ 10. The efficacy outcome was defined as neurological deterioration and stroke recurrence within 14 days. Safety outcomes included ICH and/or SAH as well as extracranial hemorrhages.

Results: Of the 1102 patients, 780 (71%) had no MBs on admission, while 230 (21%) had MBs 1-4, 48 (4%) had MBs 5-9, and 44 (4%) had MBs ≥ 10. The number of MBs was not associated with the neurological deterioration and/or stroke recurrence (p = 0.934), ICH and/or SAH (p = 0.743), and extracranial hemorrhage (p = 0.205). Favorable outcome was seem in 84% in the No MBs group, 83% in the MBs 1-4, 94% in the MBs 5-9, and 85% in the MBs ≥ 10 (p = 0.304). Combined cilostazol and aspirin therapy did not alter any rates of efficacy and safety outcomes among the no MBs, MBs 1-4, MBs 5-9, and MBs ≥ 10 groups compared to aspirin alone (all p > 0.05). By multivariate regression analysis, a history of ICH and diastolic blood pressure were the independent parameters to all of the MBs criteria (presence, MBs ≥ 5, and MBs ≥ 10).

Conclusions: MBs did not alter the clinical outcome at 3 months of onset. Elevated diastolic blood pressure and a history of ICH were the essential parameters related to the MBs.
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http://dx.doi.org/10.1016/j.jocn.2021.04.028DOI Listing
July 2021

Identification of predictors for mini-mental state examination and revised Hasegawa's Dementia Scale scores using MR-based brain morphometry.

Eur J Radiol Open 2021 24;8:100359. Epub 2021 May 24.

Department of Radiology, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka, 810-0065, Japan.

Purpose: The early detection of cognitive function decline is crucial to help manage or slow the progression of symptoms. The Mini-Mental State Examination (MMSE) and revised Hasegawa's Dementia Scale (HDS-R) are widely used in screening for cognitive impairment. The purpose of this study was to explore common predictors of the two different cognitive testing systems using MR-based brain morphometry.

Materials And Methods: This retrospective study included 200 subjects with clinical suspicion of cognitive impairment who underwent 3D T1-weighted MRI at our institution between February 2019 and August 2020. Variables related to the volume of deep gray matter and 70 cortical thicknesses were obtained from the MR images using voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) and FreeSurfer software. The correlation between each variable including age and MMSE/HDS-R scores was evaluated using uni- and multi-variate logistic regression analyses.

Results: In univariate analysis, parameters include hippocampal volume and bilateral entorhinal cortex (ERC) thickness showed moderate correlation coefficients with both MMSE and HDS-R scores. Multivariate analysis demonstrated the right ERC thickness was the common parameter which significantly correlates with both MMSE and HDS-R scores (p < 0.05).

Conclusion: Right ERC thickness appears to offer a useful predictive biomarker for both MMSE and HDS-R scores.
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http://dx.doi.org/10.1016/j.ejro.2021.100359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167144PMC
May 2021

Left Atrial Appendage Flow Velocity and Multiple Infarcts in Cryptogenic Stroke.

Cerebrovasc Dis 2021 30;50(4):429-434. Epub 2021 Mar 30.

Department of Cerebrovascular Medicine and Neurology, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.

Background: To validate the hypothesis that cryptogenic stroke with multiple infarcts included embolic stroke due to left atrial appendage (LAA) dysfunction, the present retrospective observational study was aimed to clarify the association between LAA flow velocity (LAA-FV) and multiple infarcts in patients with cryptogenic stroke.

Methods: From consecutive patients with cryptogenic stroke admitted to our hospital within 7 days after onset, patients without brain magnetic resonance imaging (MRI) on admission or without transesophageal echocardiography (TEE) during acute hospitalization were excluded, and the remaining patients were enrolled. Multiplicity of fresh infarcts was assessed using diffusion-weighted images from brain MRI. LAA-FV was defined as LAA peak emptying flow velocity on TEE.

Results: Of 786 enrolled patients, 522 patients (66%) had a single infarct, and the remaining 264 patients (34%) had multiple infarcts. The percentage of multiple infarcts decreased with increasing quartiles of LAA-FV (p for trend <0.001). The adjusted odds ratio for multiple infarcts decreased with increasing quartiles of LAA-FV (adjusted odds ratio in the fourth quartile, 0.39; 95% confidence interval, 0.25-0.60; compared with the first quartile). LAA-FV as a continuous variable was negatively associated with multiple infarcts (adjusted odds ratio per 10 cm/s, 0.87; 95% confidence interval, 0.81-0.92).

Conclusions: Reduced LAA-FV on TEE was associated with multiple infarcts in patients with cryptogenic stroke. The present findings indicate that cryptogenic stroke with multiple infarcts includes embolic stroke due to LAA dysfunction.
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http://dx.doi.org/10.1159/000514672DOI Listing
August 2021

Carotid ultrasonography predicts collateral development following combined direct and indirect revascularization surgery in adult ischemic Moyamoya disease.

Clin Neurol Neurosurg 2021 Apr 3;203:106590. Epub 2021 Mar 3.

Department of Neurosurgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.

Objective: The relationship between carotid ultrasonographic parameters and postoperative collateral development in adult ischemic moyamoya disease (MMD) patients who received combined direct and indirect revascularization surgery remains unclear. Herein, we investigated the postoperative changes in carotid ultrasonographic parameters in patients with adult ischemic MMD.

Methods: We studied 28 adult ischemic MMD patients (31 hemispheres) who underwent combined revascularization surgery. Patients underwent preoperative and postoperative (within 14 days and 3, 12, and 24 months after surgery) magnetic resonance imaging and carotid ultrasonography. We defined the hemisphere in which all signal intensities of the superficial temporal, middle meningeal, and deep temporal arteries were increased compared with that before surgery on magnetic resonance angiography as well-developed collateral establishment.

Results: Patients with good collateral establishment on MRA at 2-year after surgery had a lower external carotid artery (ECA) pulsatility index (PI) (P = 0.0413) and ECA/internal carotid artery (ICA) pulsatility index (PI) ratio (P = 0.0427) at 3-month post-operation. At 3-month post-operation, a cut-off ECA PI of 1.416 (sensitivity 40.0 %, specificity 92.3 %, area under the curve 0.7282, likelihood ratio 5.20, P = 0.0404) and ECA/ICA PI ratio of 0.8768 (sensitivity 50.0 %, specificity 92.31 %, area under the curve 0.7308, likelihood ratio 6.50, P = 0.0415) provided reliable values for good prediction of collateral development at 2 years after revascularization.

Conclusion: ECA/ICA PI ratio and ECA PI at 3-month after surgery can be one of the indicators for predicting future well-developed neovascularization on MRA and better outcome in patients with adult ischemic MMD who received combined direct and indirect revascularization surgery.
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http://dx.doi.org/10.1016/j.clineuro.2021.106590DOI Listing
April 2021

A practical system that enables physicians to respond expeditiously to significant unexpected findings (SUFs) in radiological reports.

Jpn J Radiol 2021 May 1;39(5):424-432. Epub 2021 Jan 1.

The Director of the hospital, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka City, Fukuoka Province, Japan.

Purpose: To demonstrate effectiveness of our present radiological report check flowchart enabling physicians to respond to significant unexpected findings (SUFs), by comparing the response periods from the examination date to the action date on untreated SUFs between the previous and present versions of our flowchart.

Methods: In the flowchart's previous version used February-October 2019, SUFs, which were notified by email, were audited every month. The physician received a phone call and was asked to act on the untreated SUF. In the flowchart's present version used from November 2019 to May 2020, SUFs were audited every 2 weeks. The physician and his/her chief were asked to return a written response to the untreated SUF. We evaluated the difference in the response periods between the previous and present versions of the flowchart.

Results: With the previous flowchart's use, untreated SUFs were 43 of 229 SUFs (18.8%) with the present flowchart untreated SUFs were 22 of 130 SUFs (16.9%). All SUFs in both periods were eventually responded. The present flowchart (median/range, 25/11-70 days) significantly had shorter response periods than the previous flowchart (70/16-290 days) (p < 0.0001).

Conclusion: The present flowchart employing a shortened primary audit interval, a written response, and the department chief's intervention, helped reduce the response periods.
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http://dx.doi.org/10.1007/s11604-020-01077-2DOI Listing
May 2021

Cilostazol Addition to Aspirin could not Reduce the Neurological Deterioration in TOAST Subtypes: ADS Post-Hoc Analysis.

J Stroke Cerebrovasc Dis 2021 Feb 2;30(2):105494. Epub 2020 Dec 2.

Department of Neurological Science, Nippon Medical School Graduate School of Medicine, 1-1-5, Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan; Department of Stroke Medicine, Kawasaki Medical School, Kurashiki, Japan.

Background: Our previous trial acute dual study (ADS) reported that dual antiplatelet therapy (DAPT) using cilostazol and aspirin did not reduce the rate of short-term neurological worsening in non-cardioembolic stroke patients. Present post-hoc analysis investigated whether the impact of combined cilostazol and aspirin differed among stroke subtypes and factors associated with neurological deterioration and/or stroke recurrence.

Methods: Using the ADS registry, the rate of neurological deterioration, defined as clinical worsening and/or recurrent stroke, including transient ischemic attack was calculated. Stroke subtypes included large-artery atherosclerosis (LAA), small vessel occlusion (SVO), other determined etiology (Others), and undetermined etiology of stroke (Undetermined).

Results: Data of 1022 patients were analyzed. Deterioration was seen in 104 (10%) patients, and the rates were not markedly different between patients treated with DAPT vs. aspirin in any stroke subtypes: LAA, 19% vs. 11%, (p=0.192); SVO, 10% vs. 10% (p=1.000); Others, 6% vs. 6% (p=1.000); Undetermined, 11% vs. 8% (p=0.590). Diabetes mellitus was the independent factor associated with deterioration (odds ratio 4.360, 95% confidence interval 1.139-16.691, p=0.032) in the LAA group. Age (1.030 [1.004-1.057], p=0.026), systolic blood pressure (1.012 [1.003-1.022], p=0.010), and infarct size (2.550 [1.488-4.371], p=0.001) were associated with deterioration in SVO group, and intracranial stenosis/occlusion was associated with it in the Undetermined group (3.744 [1.138-12.318], p=0.030).

Conclusions: Combined cilostazol and aspirin did not reduce the rate of short-term neurological deterioration in any clinical stroke subtype. The characteristics of patients whose condition deteriorates in the acute period may differ based on the stroke subtypes.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105494DOI Listing
February 2021

Information physics of living matters.

Biophys Physicobiol 2020 10;17:130-131. Epub 2020 Sep 10.

Laboratory for Cell Polarity Regulation, RIKEN Center for Biosystems Dynamics Research (BDR), Suita, Osaka 565-0874, Japan.

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http://dx.doi.org/10.2142/biophysico.BSJ-2020024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671737PMC
September 2020

NUDT21 Links Mitochondrial IPS-1 to RLR-Containing Stress Granules and Activates Host Antiviral Defense.

J Immunol 2021 01 20;206(1):154-163. Epub 2020 Nov 20.

Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.

Viral RNA in the cytoplasm of mammalian host cells is recognized by retinoic acid-inducible protein-I-like receptors (RLRs), which localize to cytoplasmic stress granules (SGs). Activated RLRs associate with the mitochondrial adaptor protein IPS-1, which activates antiviral host defense mechanisms, including type I IFN induction. It has remained unclear, however, how RLRs in SGs and IPS-1 in the mitochondrial outer membrane associate physically and engage in information transfer. In this study, we show that NUDT21, an RNA-binding protein that regulates alternative transcript polyadenylation, physically associates with IPS-1 and mediates its localization to SGs in response to transfection with polyinosinic-polycytidylic acid [poly(I:C)], a mimic of viral dsRNA. We found that despite its well-established function in the nucleus, a fraction of NUDT21 localizes to mitochondria in resting cells and becomes localized to SGs in response to poly(I:C) transfection. NUDT21 was also found to be required for efficient type I IFN induction in response to viral infection in both human HeLa cells and mouse macrophage cell line RAW264.7 cells. Our results together indicate that NUDT21 links RLRs in SGs to mitochondrial IPS-1 and thereby activates host defense responses to viral infection.
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http://dx.doi.org/10.4049/jimmunol.2000306DOI Listing
January 2021

Left Atrial Size and Ischemic Events after Ischemic Stroke or Transient Ischemic Attack in Patients with Nonvalvular Atrial Fibrillation.

Cerebrovasc Dis 2020 11;49(6):619-624. Epub 2020 Nov 11.

Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.

Background: The present study aimed to clarify the association between left atrial (LA) size and ischemic events after ischemic stroke or transient ischemic attack (TIA) in patients with nonvalvular atrial fibrillation (NVAF).

Methods: Acute ischemic stroke or TIA patients with NVAF were enrolled. LA size was classified into normal LA size, mild LA enlargement (LAE), moderate LAE, and severe LAE. The ischemic event was defined as ischemic stroke, TIA, carotid endarterectomy, carotid artery stenting, acute coronary syndrome or percutaneous coronary intervention, systemic embolism, aortic aneurysm rupture or dissection, peripheral artery disease requiring hospitalization, or venous thromboembolism.

Results: A total of 1,043 patients (mean age, 78 years; 450 women) including 1,002 ischemic stroke and 41 TIA were analyzed. Of these, 351 patients (34%) had normal LA size, 298 (29%) had mild LAE, 198 (19%) had moderate LAE, and the remaining 196 (19%) had severe LAE. The median follow-up duration was 2.0 years (interquartile range, 0.9-2.1). During follow-up, 117 patients (11%) developed at least one ischemic event. The incidence rate of total ischemic events increased with increasing LA size. Severe LAE was independently associated with increased risk of ischemic events compared with normal LA size (multivariable-adjusted hazard ratio, 1.75; 95% confidence interval, 1.02-3.00).

Conclusion: Severe LAE was associated with increased risk of ischemic events after ischemic stroke or TIA in patients with NVAF.
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http://dx.doi.org/10.1159/000511393DOI Listing
March 2021

Japanese and Non-Japanese Patients with Transient Ischemic Attack or Minor Stroke: A Five-Year Risk Analysis of Stroke and Vascular Events.

J Atheroscler Thromb 2021 Jun 17;28(6):656-664. Epub 2020 Sep 17.

Department of Neurology and Stroke Center, Bichat Hospital.

Aims: We have previously reported 5-year follow-up data on the TIAregistry.org, an international prospective cohort in patients with transient ischemic attack (TIA) or minor stroke. We conducted a Japanese subgroup analysis because outcomes and predictors might differ according to ethnicities and regions. In this study, we compared the baseline and 5-year follow-up data of Japanese and non-Japanese patients with TIA or minor stroke.

Methods: Patients with TIA or minor ischemic stroke within 7 days after the onset were classified into two groups based on ethnicity, Japanese (n=345) and non-Japanese (n=3502); further, 5-year event rates were compared between the two groups. We also determined predictors of 5-year stroke for both groups.

Results: Vascular death and death from any cause were identified to be less prevalent, unlike stroke and intracranial hemorrhage, which was determined to be more prevalent in Japanese than in non-Japanese patients. Five-year rate of stroke was significantly higher in Japanese patients. Cumulative stroke and major cardiovascular event rates did not decline but instead linearly increased from 1 to 5 years in both groups. Baseline risk factors for 5-year stroke were as follows: age, diabetes, history of stroke or TIA, and congestive heart failure in Japanese patients. Independent predictors of 5-year stroke were large artery atherosclerosis, congestive heart failure, diabetes, and age in Japanese patients.

Conclusions: Recurrent stroke and intracranial hemorrhage were determined to be more prevalent at 5 years after TIA or minor stroke in Japanese patients than in non-Japanese patients. Strategies to mitigate the long-term risks of stroke, aside from adherence to current guidelines, should take Japanese-patient-specific residual risks into account.
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http://dx.doi.org/10.5551/jat.58552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219541PMC
June 2021

Atrial Fibrillation After Ischemic Stroke Detected by Chest Strap-Style 7-Day Holter Monitoring and the Risk Predictors: EDUCATE-ESUS.

J Atheroscler Thromb 2021 May 15;28(5):544-554. Epub 2020 Aug 15.

Department of Cerebrovascular Medicine and Neurology, National Hospital Organization Kyushu Medical Center.

Aim: This study aimed to investigate the diagnostic yield of 7-day Holter monitoring for detecting covert atrial fibrillation (AF) in patients with recent embolic stroke of undetermined source (ESUS) and to identify the pre-entry screening biomarkers that had significant associations with later detection of AF (clinicaltrials.gov. NCT02801708).

Methods: A total of 206 patients who have recent ESUS without previously documented AF underwent Holter electrocardiography using a chest strap-style monitor. External validation of biomarkers predictive of AF was performed using 83 patients with ESUS who were implanted with insertable cardiac monitors.

Results: The 7-day Holter monitoring started at a median of 13 days after the onset of stroke. AF was detected in 14 patients, and three of these showed a single AF episode lasting <2 min. The median time delay to the first documented AF was 50 h. Each of serum brain natriuretic peptide ≥ 66.0 pg/mL (adjusted odds ratio 5.23), atrial premature contractions (APCs) ≥ 345 beats (3.80), and APC short runs ≥ 13 (5.74) on 24-h Holter prior to the 7-day Holter showed a significant association with detection of AF, independent of age and physiological findings in this derivation cohort, and all of these showed a significant association in the validation cohort (adjusted odds ratio 6.59, 7.87, and 6.16, respectively).

Conclusions: In recent ESUS patients, the detection rate of AF using the 7-day Holter monitoring was 6.8% (95% CI 4.1%-11.1%). Brain natriuretic peptide, APC count, and APC short runs in the standard clinical workup seemed to be predictors of covert AF.
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http://dx.doi.org/10.5551/jat.58420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193782PMC
May 2021

Ischemic Stroke Caused by Carotid Stump at the Common Carotid Artery.

Intern Med 2020 Dec 28;59(23):3071-3074. Epub 2020 Jul 28.

Division of Cerebrovascular Medicine and Neurology, Clinical Research Institute, National Hospitalization Organization, Kyushu Medical Center, Japan.

An 84-year-old man developed motor aphasia and right hemiparesis on postoperative day 1 after orchiectomy for suspected malignant lymphoma. He had a history of thoracic endovascular aortic repair for aortic aneurysm using a bypass graft from the right subclavian artery to the left common carotid artery (CCA); however, the graft had become occluded six months later. Brain magnetic resonance imaging revealed acute cerebral infarctions in the left frontal lobe. Carotid ultrasonography revealed a stump at the left CCA, just below the bifurcation, formed by the occluded graft with an oscillating thrombus. This case was rare in that a CCA stump was identified as the embolic source of ischemic stroke.
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http://dx.doi.org/10.2169/internalmedicine.5021-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759691PMC
December 2020

Neurological Disorders Identified during Treatment of a SARS-CoV-2 Infection.

Intern Med 2020 Sep 21;59(17):2187-2189. Epub 2020 Jul 21.

Division of Cerebrovascular Medicine and Neurology, Clinical Research Institute, National Hospitalization Organization, Kyushu Medical Center, Japan.

A 69-year-old man was admitted to our hospital under diagnosis of pneumonia due to severe acute respiratory syndrome-corona virus 2 (SARS-CoV-2) (Day 0). He underwent endotracheal intubation from Day 3. Although his respiratory condition improved and anesthetic drugs were discontinued, no cough reflex was observed despite intubation having been performed until Day 17. His tendon reflexes were also diminished. We suspected that he had developed Guillain-Barré syndrome (GBS), and administered intravenous immunoglobulin from Day 18. The absence of cough reflex improved and extubation was successfully performed on Day 23. Neurological disorders including GBS should be considered when intubated SARS-CoV-2 patients present with a loss of cough reflex during the treatment period.
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http://dx.doi.org/10.2169/internalmedicine.5447-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516316PMC
September 2020

Sex Differences in Blood Pressure-Lowering Therapy and Outcomes Following Intracerebral Hemorrhage: Results From ATACH-2.

Stroke 2020 08 6;51(8):2282-2286. Epub 2020 Jul 6.

Department of Cerebrovascular Medicine (M.F.-D., M.K., S.Y., K.M., K.T.), National Cerebral and Cardiovascular Center, Suita, Japan.

Background And Purpose: Evidence regarding sex differences in clinical outcomes and treatment effect following intracerebral hemorrhage is limited. Using the ATACH-2 trial (Antihypertensive Treatment in Intracerebral Hemorrhage-2) data, we explored whether sex disparities exist in outcomes and response to intensive blood pressure (BP)-lowering therapy.

Methods: Eligible intracerebral hemorrhage subjects were randomly assigned to intensive (target systolic BP, 110-139 mm Hg) or standard (140-179 mm Hg) BP-lowering therapy within 4.5 hours after onset. Relative risk of death or disability corresponding to the modified Rankin Scale score of 4 to 6 was calculated, and interaction between sex and treatment was explored.

Results: In total, 380 women and 620 men were included. Women were older, more prescribed antihypertensive drugs before onset, and had more lobar intracerebral hemorrhage than men. Hematoma expansion was observed less in women. After multivariable adjustment, the relative risk of death or disability in women was 1.19 (95% CI, 1.02-1.37, =0.023). The relative risk of death or disability between intensive versus standard BP-lowering therapy was 0.91 (95% CI, 0.74-1.13) in women versus 1.13 (95% CI, 0.92-1.39) in men ( for interaction=0.11), with inconclusive Gail-Simmon test (=0.16).

Conclusions: Women had a higher risk of death or disability following intracerebral hemorrhage. The benefit of intensive BP-lowering therapy in women is inconclusive, consistent with the overall results of ATACH-2. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01176565.
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http://dx.doi.org/10.1161/STROKEAHA.120.029770DOI Listing
August 2020

Recurrent Guillain-Barré and Fisher Syndromes in Two Patients Who Were Subsequently Diagnosed with Aplastic Anemia.

Case Rep Neurol 2020 May-Aug;12(2):148-152. Epub 2020 May 28.

Division of Cerebrovascular Medicine and Neurology, Clinical Research Institute, National Hospitalization Organization, Kyushu Medical Center, Fukuoka, Japan.

Guillain-Barré (GBS) and Fisher (FS) syndromes rarely recur and the characteristics of recurrence have not been fully elucidated. We describe the cases of 2 patients with GBS or FS that recurred more than twice and who were subsequently diagnosed with aplastic anemia. Case 1 was a 66-year-old man who was diagnosed with aplastic anemia 10 months before admission with limb ataxia and a sensory disturbance of the distal limbs that developed 3 days after an upper respiratory tract infection. He had a history of double vision with ataxia at the ages of 38 and 56 years. Case 2 was a 66-year-old woman who had been treated for aplastic anemia 1 year previously. She had a history of upper limb weakness after upper respiratory tract infections at the ages of 39 and 60 years. Tendon reflexes were absent in both patients at the time of onset and they were respectively diagnosed with FS and GBS and treated with intravenous immunoglobulin. No neurological deficits persisted. Blood findings showed that both were positive for IgG type ganglioside antibodies and HLA-DR15. The positive HLA-DR15 might have been associated with the recurrent GBS or FS and the development of aplastic anemia.
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http://dx.doi.org/10.1159/000507778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315140PMC
May 2020

Robust classification of cell cycle phase and biological feature extraction by image-based deep learning.

Mol Biol Cell 2020 06 22;31(13):1346-1354. Epub 2020 Apr 22.

Department of Cell Biology and Anatomy and International Research Center for Neurointelligence (WPI-IRCN), Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.

Across the cell cycle, the subcellular organization undergoes major spatiotemporal changes that could in principle contain biological features that could potentially represent cell cycle phase. We applied convolutional neural network-based classifiers to extract such putative features from the fluorescence microscope images of cells stained for the nucleus, the Golgi apparatus, and the microtubule cytoskeleton. We demonstrate that cell images can be robustly classified according to G1/S and G2 cell cycle phases without the need for specific cell cycle markers. Grad-CAM analysis of the classification models enabled us to extract several pairs of quantitative parameters of specific subcellular features as good classifiers for the cell cycle phase. These results collectively demonstrate that machine learning-based image processing is useful to extract biological features underlying cellular phenomena of interest in an unbiased and data-driven manner.
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http://dx.doi.org/10.1091/mbc.E20-03-0187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353138PMC
June 2020

Common carotid flow velocity is associated with cognitive function after carotid endarterectomy.

J Clin Neurosci 2020 Jun 17;76:53-57. Epub 2020 Apr 17.

Departments of Cerebrovascular Medicine and Neurology, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, 1-8-1, Jigyo-hama, Chuo-ku, Fukuoka 810-8563, Japan.

The relationship between ultrasonographic flow parameters and cognitive function has not been well studied. This study aimed to clarify associations between carotid flow velocity (FV) and cognitive function in patients with a history of carotid endarterectomy (CEA). Ninety-four patients who previously underwent CEA participated in this study. The Neurobehavioral Cognitive Status Examination (Cognistat) and Frontal Assessment Battery (FAB) were adopted to assess cognitive functions at a mean of 6.5 ± 3.2 years after CEA. End-diastolic flow velocity (EDV) of the left and right common carotid artery (CCA) was significantly associated with total Cognistat score (p < 0.001) and total FAB score (p < 0.05). Pulsatility index (PI) of the left CCA was significantly associated with total Cognistat score and total FAB score (p < 0.01). A cut-off right CCA EDV of 14.5 cm/s offered the most reliable predictor of the bottom 25th percentile of total Cognistat score (sensitivity 83.3%, specificity 61.0%, area under the curve (AUC) 0.731, p = 0.0060), while a cut-off left CCA PI of 1.83 was the most reliable predictor of the bottom 25th percentile of total FAB score (sensitivity 73.3%, specificity 60.0%, AUC 0.679, p = 0.0179). Left and right CCA EDV correlated with sub-components of comprehension, construction, judgment, programming (p < 0.01), and conceptualization (p < 0.05). Right CCA EDV correlated with similarity (p < 0.01), repetition, naming, and memory (p < 0.05). Left CCA PI correlated with attention, conceptualization (p < 0.01), repetition, construction, similarity, and mental flexibility (p < 0.05), while right CCA PI correlated with construction (p < 0.05). CCA FV may offer useful markers of cognitive functions in patients with a history of CEA.
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http://dx.doi.org/10.1016/j.jocn.2020.04.050DOI Listing
June 2020

Thrombolysis With Alteplase at 0.6 mg/kg for Stroke With Unknown Time of Onset: A Randomized Controlled Trial.

Stroke 2020 05 6;51(5):1530-1538. Epub 2020 Apr 6.

Department of Neurosurgery, Hyogo College of Medicine, Nishinomiya (S. Yoshimura).

Background and Purpose- We assessed whether lower-dose alteplase at 0.6 mg/kg is efficacious and safe for acute fluid-attenuated inversion recovery-negative stroke with unknown time of onset. Methods- This was an investigator-initiated, multicenter, randomized, open-label, blinded-end point trial. Patients met the standard indication criteria for intravenous thrombolysis other than a time last-known-well >4.5 hours (eg, wake-up stroke). Patients were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg or standard medical treatment if magnetic resonance imaging showed acute ischemic lesion on diffusion-weighted imaging and no marked corresponding hyperintensity on fluid-attenuated inversion recovery. The primary outcome was a favorable outcome (90-day modified Rankin Scale score of 0-1). Results- Following the early stop and positive results of the WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke), this trial was prematurely terminated with 131 of the anticipated 300 patients (55 women; mean age, 74.4±12.2 years). Favorable outcome was comparable between the alteplase group (32/68, 47.1%) and the control group (28/58, 48.3%; relative risk [RR], 0.97 [95% CI, 0.68-1.41]; =0.892). Symptomatic intracranial hemorrhage within 22 to 36 hours occurred in 1/71 and 0/60 (RR, infinity [95% CI, 0.06 to infinity]; >0.999), respectively. Death at 90 days occurred in 2/71 and 2/60 (RR, 0.85 [95% CI, 0.06-12.58]; >0.999), respectively. Conclusions- No difference in favorable outcome was seen between alteplase and control groups among patients with ischemic stroke with unknown time of onset. The safety of alteplase at 0.6 mg/kg was comparable to that of standard treatment. Early study termination precludes any definitive conclusions. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02002325.
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http://dx.doi.org/10.1161/STROKEAHA.119.028127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185058PMC
May 2020

Cilostazol uncovers covert atrial fibrillation in non-cardioembolic stroke.

J Neurol Sci 2020 06 21;413:116796. Epub 2020 Mar 21.

Department of Neurological Science, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan; Department of Stroke Medicine, Kawasaki Medical School, Kurashiki, Japan.

Background: We hypothesized that administration of cilostazol may clarify the occult atrial fibrillation (AF) during hospitalization in mild stroke patients, who has no history of AF.

Methods: From our prospective non-cardioembolic stroke study, randomized to dual antiplatelet therapy using cilostazol and aspirin or aspirin alone trial (ADS), data on the presence or absence of AF were retrospectively analyzed. In the ADS, during hospitalization, as a routine examination, presence of AF was investigated using electrocardiogram (ECG), ECG monitoring and Holter ECG. Multivariate regression analysis was conducted to evaluate the independent parameters related to the AF. Clinical outcome at 3 months was evaluated using modified Rankin Scale (mRS) score.

Results: Data on 1194 patients (793 [66%] men; median age [interquartile range] of 69 [61-77] years, National Institutes of Health Stroke Scale score 2 [1-4], onset-to-admission 10.8 [4.7-20.5] hours) were retrospectively analyzed. AF was newly detected in 41 (3%) patients (3 by ECG, 21 by the ECG monitoring and 17 by the Holter ECG) during hospitalization. Patients treated with combined cilostazol and aspirin therapy frequently had the AF than those took aspirin alone (5% vs. 2%, p = .007). Multivariate regression analysis showed that cilostazol administration was one of the independent factors for new-AF (odds ratio 2.672, 95%CI: 1.205-5.927, p = .016). The frequency of mRS 0-1 was 68% in the new-AF group and 67% in the non-AF group (p = 1.000).

Conclusion: Cilostazol therapy may increase the detectability of AF in acute non-cardioembolic stroke, though the new-AF was not related to clinical outcome at 3 months.
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http://dx.doi.org/10.1016/j.jns.2020.116796DOI Listing
June 2020
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