Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：Scientific Reports  

Smoking has detrimental effects on the cardiovascular system; however, some studies have reported better clinical outcomes after thrombolysis for ischemic stroke in smokers than in nonsmokers, a phenomenon known as the smoking paradox. Therefore, this study aimed to examine the smoking paradox in patients with ischemic stroke receiving reperfusion therapy. Data were collected from a multicenter hospital-based acute stroke registry in Fukuoka, Japan. The 1148 study patients were categorized into current and noncurrent smokers. The association between smoking and clinical outcomes, including neurological improvement (≥ 4-point decrease in the National Institutes of Health Stroke Scale during hospitalization or 0 points at discharge) and good functional outcomes (modified Rankin Scale score of 0–2) at 3 months, was evaluated using logistic regression analysis and propensity score-matched analysis. Among the participants, 231 (20.1%) were current smokers. The odds ratios (ORs) of favorable outcomes after adjusting for potential confounders were not significantly increased in current smokers (OR 0.85, 95% confidence interval [CI] 0.60–1.22 for neurological improvement; OR 0.95, 95% CI 0.65–1.38 for good functional outcome). No significant association was found in the propensity score-matched cohorts. Smoking cessation is strongly recommended since current smoking was not associated with better outcomes after reperfusion therapy.

DOI： 10.1038/s41598-024-59508-3

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Language：English   Publishing type：Research paper (scientific journal)  

Language：English  

DOI： 10.2196/46840

PubMed

Language：English   Publisher：PLoS ONE  

Background It is unclear whether abdominal adiposity has an additional effect on post-stroke outcomes. This study aimed to determine whether waist circumference (WC) is independently associated with clinical outcomes after acute ischemic stroke. Methods We enrolled patients with acute ischemic stroke from a multicenter hospital-based stroke registry in Fukuoka, Japan. We measured WC on admission and categorized patients into four groups (Q1–Q4) according to the quartiles in females and males. The clinical outcomes were poor functional outcome (modified Rankin scale score 2–6) and death from any cause. Logistic regression analysis was performed to estimate the odds ratio and 95% confidence interval of the outcomes of interest after adjusting for potential confounding factors, including body mass index (BMI). Results A total of 11,989 patients (70.3±12.2 years, females: 36.1%) were included in the analysis. The risk of poor functional outcome significantly decreased for Q2–Q4 (vs. Q1) at discharge and Q2–Q3 (vs. Q1) at 3 months, even after adjusting for potential confounders, including BMI. In contrast, adjustment of BMI eliminated the significant association between WC and all-cause death at discharge and 3 months. The association between high WC and favorable functional outcome was not affected by fasting insulin levels or homeostatic model assessment for insulin resistance and was only found in patients without diabetes (P = 0.02 for heterogeneity). Conclusions These findings suggest that abdominal adiposity has an additional impact on post-stroke functional outcome, independent of body weight and insulin action.

DOI： 10.1371/journal.pone.0296833

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Language：English   Publisher：PLoS ONE  

Background This study aimed to examine whether post-stroke early body temperature is associated with neurological damage in the acute phase and functional outcomes at three months. Methods We included 7,177 patients with acute ischemic stroke within 24 h of onset. Axillary temperature was measured daily in the morning for seven days. Mean body temperature was grouped into five quintiles (Q1: 35.1–36.5◦C, Q2: 36.5–36.7◦C, Q3: 36.7–36.8◦C, Q4: 36.8–37.1◦C, and Q5: 37.1–39.1◦C). Clinical outcomes included neurological improvement during hospitalization and poor functional outcome (modified Rankin scale score, 3–6) at three months. A logistic regression analysis was performed to evaluate the association between body temperature and clinical outcomes. Results The patient’s mean (SD) age was 70.6 (12.3) years, and 35.7% of patients were women. Mean body temperature was significantly associated with less neurological improvement from Q2 (odds ratios [95% confidence interval], 0.77 [0.65–0.99] vs. Q1) to Q5 (0.33 [0.28–0.40], P for trend <0.001) even after adjusting for potential confounders, including baseline neurological severity, C-reactive protein levels, and post-stroke acute infections. The multivariable-adjusted risk of poor functional outcome linearly increased from Q2 (1.36 [1.03–1.79]) to Q5 (6.44 [5.19–8.96], P for trend <0.001). These associations were maintained even in the analyses excluding patients with acute infectious diseases. Multivariable-adjusted risk of poor functional outcome was higher in patients with early body temperature elevation on days 1–3 and with longer duration with body temperature >37.0◦C. Conclusions Post-stroke early high body temperature is independently associated with unfavorable outcomes following acute ischemic stroke.

DOI： 10.1371/journal.pone.0296639

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：Cerebrovascular Diseases  

Introduction: Data on sex differences in poststroke functional status for a period longer than 1 year based on large cohorts are sparse. This study aimed to determine whether there are sex differences in long-term functional decline after ischemic stroke. Methods: We tracked functional status for 5 years among 3-month survivors of acute ischemic stroke and compared outcomes between women and men using a large-scale hospital-based stroke registry in Fukuoka, Japan. Functional status was assessed using the modified Rankin Scale (mRS). Functional dependency was defined as an mRS score of 3, 4, or 5. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals of outcomes after adjusting for possible confounders. Results: A total of 8,446 patients (71.9 ± 12.5 years, 3,377 (40.0%) female patients) were enrolled in this study. Female sex was associated with a higher risk of functional dependency at 5 years poststroke even when adjusting for age, 3-month mRS score, and other confounding factors (multivariable-adjusted OR vs. men, 1.56 [95% confidence interval, 1.26-1.93]). This significant association of female sex with higher dependency at 5 years was also found among patients who were independent at 3 months poststroke. Subgroup analysis showed that increased risk of functional dependency in female patients was more marked in patients aged ≥75 years than in those aged <75 years (p for heterogeneity = 0.02). Conversely, female sex was associated with a lower risk of death. No sex difference was observed in stroke recurrence during 5 years poststroke. Discussion/Conclusion: This longitudinal observational study suggests that female sex was independently associated with an increased risk of functional decline in the chronic phase of stroke, especially in older patients. There was no sex difference in 5-year stroke recurrence, and thus, other factors might be involved in more significant deterioration of functional status in female survivors of ischemic stroke. Further studies are needed to elucidate underlying causes of sex differences in long-term functional decline after stroke.

DOI： 10.1159/000526940

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Language：Japanese   Publisher：(一社)日本神経学会  

症例は41歳女性.40歳時に右中大脳動脈領域の塞栓源不明脳塞栓症の既往があり,植込み型心電図記録計の留置とダビガトラン内服が開始となった.41歳時に再び構音障害と左片麻痺が出現した.頭部MRI拡散強調画像で右放線冠の急性期脳梗塞とMRAで右中大脳動脈M2分枝閉塞を認めた.頸動脈エコーでは右頸動脈球部に可動性プラーク様構造物を認め,頸動脈3次元CTangiographyでは同部後面から突出する構造物を呈し,carotid webと診断した.待機的に頸動脈内膜剥離術を施行し,病理学的に線維筋性異形成による血管形態異常であることを確認した.(著者抄録)

Publisher：東京医学社  

DOI： 10.24479/kd.0000000848

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Language：English   Publisher：PLoS ONE  

Background The association between clinical outcomes in ischemic stroke patients and decreases in serum uric acid levels, which often occur during the acute phase, remains unknown. Herein, we aimed to investigate the association using a large-scale, multicenter stroke registry. Methods We analyzed 4,621 acute ischemic stroke patients enrolled in the Fukuoka Stroke Registry between June 2007 and September 2019 whose uric acid levels were measured at least twice during hospitalization (including on admission). The study outcomes were poor functional outcome (modified Rankin Scale score ≥3) and functional dependence (modified Rankin Scale score 3–5) at 3 months after stroke onset. Changes in uric acid levels after admission were evaluated using a decrease rate that was classified into 4 sex-specific grades ranging from G1 (no change/increase after admission) to G4 (most decreased). Multivariable logistic regression analyses were used to assess the associations between decreases in uric acid levels and the outcomes. Results The frequencies of the poor functional outcome and functional dependence were lowest in G1 and highest in G4. The odds ratios (95% confidence intervals) of G4 were significantly higher for poor functional outcome (2.66 [2.05–3.44]) and functional dependence (2.61 [2.00–3.42]) when compared with G1 after adjusting for confounding factors. We observed no heterogeneity in results for subgroups categorized according to age, sex, stroke subtype, neurological severity, chronic kidney disease, or uric acid level on admission. Conclusions Decreases in serum uric acid levels were independently associated with unfavorable outcomes after acute ischemic stroke.

DOI： 10.1371/journal.pone.0287721

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Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：Scientific Reports  

This study aimed to determine whether body weight is associated with functional outcome after acute ischemic stroke. We measured the body mass index (BMI) and assessed clinical outcomes in patients with acute ischemic stroke. The BMI was categorized into underweight (< 18.5 kg/m2), normal weight (18.5–22.9 kg/m2), overweight (23.0–24.9 kg/m2), and obesity (≥ 25.0 kg/m2). The association between BMI and a poor functional outcome (modified Rankin Scale [mRS] score: 3–6) was evaluated. We included 11,749 patients with acute ischemic stroke (70.3 ± 12.2 years, 36.1% women). The risk of a 3-month poor functional outcome was higher for underweight, lower for overweight, and did not change for obesity in reference to a normal weight even after adjusting for covariates by logistic regression analysis. Restricted cubic splines and SHapley Additive exPlanation values in eXtreme Gradient Boosting model also showed non-linear relationships. Associations between BMI and a poor functional outcome were maintained even after excluding death (mRS score: 3–5) or including mild disability (mRS score: 2–6) as the outcome. The associations were strong in older patients, non-diabetic patients, and patients with mild stroke. Body weight has a non-linear relationship with the risk of a poor functional outcome after acute ischemic stroke.

DOI： 10.1038/s41598-023-35894-y

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Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：Stroke  

Background: It remains unclear how chronic kidney disease and its underlying pathological conditions, kidney dysfunction, and kidney damage, are associated with cardiovascular outcomes. This study aimed to determine whether kidney dysfunction (ie, decreased estimated glomerular filtration rate), kidney damage (ie, proteinuria), or both are associated with the long-term outcomes after ischemic stroke. Methods: A total of 12 576 patients (mean age, 73.0±12.6 years; 41.3% women) with ischemic stroke who were registered in a hospital-based multicenter registry, Fukuoka Stroke Registry, between June 2007 and September 2019, were prospectively followed up after stroke onset. Kidney function was assessed by estimated glomerular filtration rate and categorized into G1: ≥60 mL/(min·1.73 m2), G2: 45-59 mL/(min·1.73 m2), and G3: <45 mL/(min·1.73 m2). Kidney damage was evaluated by proteinuria using a urine dipstick test and classified into P1: -, P2: ±/1+, and P3: ≥2+. Hazard ratios and 95% CI for events of interest were estimated by a Cox proportional hazards model. Long-term outcomes included recurrence of stroke and all-cause death. Results: During the median follow-up of 4.3 years (interquartile range, 2.1-7.3 years), 2481 patients had recurrent stroke (48.0/1000 patient-years) and 4032 patients died (67.3/1000 patient-years). Chronic kidney disease was independently associated with increased risks of stroke recurrence and all-cause death even after adjustment for multiple confounding factors, including traditional cardiovascular risk factors. Both estimated glomerular filtration rate and proteinuria were independently associated with increased risks of stroke recurrence (multivariable-adjusted hazard ratio [95% CI], G3: 1.22 [1.09-1.37] versus G1, P3: 1.25 [1.07-1.46] versus P1) and death (G3: 1.45 [1.33-1.57] versus G1, P3: 1.62 [1.45-1.81] versus P1). In subgroup analyses, effect modifications were found in the association of proteinuria with death by age and stroke subtype. Conclusions: Kidney dysfunction and kidney damage were independently, but differently, associated with increased risks of recurrent stroke and all-cause death.

DOI： 10.1161/STROKEAHA.122.040958

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Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：Journal of Cerebral Blood Flow and Metabolism  

Post-stroke intra-infarct repair promotes peri-infarct neural reorganization leading to functional recovery. Herein, we examined the remodeling of extracellular matrix proteins (ECM) that constitute the intact basal membrane after permanent middle cerebral artery occlusion (pMCAO) in mice. Among ECM, collagen type IV remained localized on small vessel walls surrounding CD31-positive endothelial cells within infarct areas. Fibronectin was gradually deposited from peri-infarct areas to the ischemic core, in parallel with the accumulation of PDGFRβ-positive cells. Cultured PDGFRβ-positive pericytes produced fibronectin, which was enhanced by the treatment with PDGF-BB. Intra-infarct deposition of fibronectin was significantly attenuated in pericyte-deficient Pdgfrb+/− mice. Phagocytic activity of macrophages against myelin debris was significantly enhanced on fibronectin-coated dishes. In contrast, laminin α2, produced by GFAP- and aquaporin 4-positive astrocytes, accumulated strongly in the boundary of peri-infarct areas. Pericyte-conditioned medium increased the expression of laminin α2 in cultured astrocytes, partly through TGFβ1. Laminin α2 increased the differentiation of oligodendrocyte precursor cells into oligodendrocytes and the expression of myelin-associated proteins. Peri-infarct deposition of laminin α2 was significantly reduced in Pdgfrb+/− mice, with attenuated oligodendrogenesis in peri-infarct areas. Collectively, intra-infarct PDGFRβ-positive cells may orchestrate post-stroke remodeling of key ECM that create optimal environments promoting clearance of myelin debris and peri-infarct oligodendrogenesis.

DOI： 10.1177/0271678X221145092

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Language：English   Publisher：Journal of the Neurological Sciences  

Background and purpose: This study examined the association between age and clinical outcomes after ischemic stroke, and whether the effect of age on post-stroke outcomes can be modified by various factors. Methods: We included 12,171 patients with acute ischemic stroke, who were functionally independent before stroke onset, in a multicenter hospital-based study conducted in Fukuoka, Japan. Patients were categorized into six groups according to age: ≤ 45, 46–55, 56–65, 66–75, 76–85, and > 85 years. Logistic regression analysis was performed to estimate an odds ratio for poor functional outcome (modified Rankin scale score of 3–6 at 3 months) for each age group. Interaction effects of age and various factors were analyzed using a multivariable model. Results: The mean age of the patients was 70.3 ± 12.2 years, and 63.9% were men. Neurological deficits at onset were more severe in the older age groups. The odds ratio of poor functional outcome linearly increased (P for trend <0.001), even after adjusting for potential confounders. Sex, body mass index, hypertension, and diabetes mellitus significantly modified the effect of age on the outcome (P < 0.05). The unfavorable effect of older age was greater in female patients and those with low body weight, whereas the protective effect of younger age was smaller in patients with hypertension or diabetes mellitus. Conclusions: Functional outcome worsened with age in patients with acute ischemic stroke, especially in females and those with low body weight, hypertension, or hyperglycemia.

DOI： 10.1016/j.jns.2023.120589

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Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：GLIA  

NOX4 is a major reactive oxygen species-producing enzyme that modulates cell stress responses. We here examined the effect of Nox4 deletion on demyelination–remyelination, the most common pathological change in the brain. We used a model of cuprizone (CPZ)-associated demyelination–remyelination in wild-type and Nox4-deficient (Nox4−/−) mice. While the CPZ-induced demyelination in the corpus callosum after 4 weeks of CPZ intoxication was slightly less pronounced in Nox4−/− mice than that in wild-type mice, remyelination following CPZ withdrawal was significantly enhanced in Nox4−/− mice with an increased accumulation of IBA1-positive microglia/macrophages in the demyelinating corpus callosum. Consistently, locomotor function, as assessed by the beam walking test, was significantly better during the remyelination phase in Nox4−/− mice. Nox4 deletion did not affect autonomous growth of primary-culture oligodendrocyte precursor cells. Although Nox4 expression was higher in cultured macrophages than in microglia, Nox4−/− microglia and macrophages both showed enhanced phagocytic capacity of myelin debris and produced increased amounts of trophic factors upon phagocytosis. The expression of trophic factors was higher, in parallel with the accumulation of IBA1-positive cells, in the corpus callosum in Nox4−/− mice than that in wild-type mice. Nox4 deletion suppressed phagocytosis-induced increase in mitochondrial membrane potential, enhancing phagocytic capacity of macrophages. Treatment with culture medium of Nox4−/− macrophages engulfing myelin debris, but not that of Nox4−/− astrocytes, enhanced cell growth and expression of myelin-associated proteins in cultured oligodendrocyte precursor cells. Collectively, Nox4 deletion promoted remyelination after CPZ-induced demyelination by enhancing microglia/macrophage-mediated clearance of myelin debris and the production of trophic factors leading to oligodendrogenesis.

DOI： 10.1002/glia.24292

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Language：English   Publisher：Cerebrovascular Diseases  

Background: Little is known about the association between poststroke cognitive impairment (PSCI) and functional outcome in the acute care phase of ischemic stroke and the influence of the clinical condition of acute stroke on this association. We examined this issue, taking into account stroke-related factors, in a hospital-based prospective study of patients with acute ischemic stroke. The same analysis was also performed after subsequent rehabilitation to investigate whether the association observed in the acute care phase persisted after that. For comparison, the same analysis was performed for pre-stroke dementia (PreSD). Methods: We included in the study a total of 923 patients with acute ischemic stroke who were admitted to a hospital from 2012 to 2020 in Japan. Cognitive function was assessed using the Mini-Mental State Examination and Raven's Colored Progressive Matrices test at an average of 6.3 days after stroke onset. The subjects were divided into three groups with normal cognition, PSCI, and PreSD. Study outcome was a poor functional outcome, defined as a modified Rankin Scale score of ≥3 at the end of acute care (median 21 days after admission). Among total subjects, 460 were also assessed for poor functional outcome after rehabilitation (median 77 days after admission). A logistic regression model was applied in this study. Results: Patients with PSCI and PreSD had higher median National Institute of Health Stroke Scale scores than those with normal cognition (median [IQR]: 3 [2-6], 4 [2-12], and 2 [1-4], respectively). The age- and sex-adjusted cumulative incidence of poor functional outcome was significantly higher in patients with PSCI and PreSD than in those with normal cognition in the acute care and rehabilitation phases. In the acute care phase, these associations remained significant after adjustment for stroke-related factors and other confounders (multivariable-adjusted odds ratio [95% CI] for PSCI vs. normal cognition: 3.28 [2.07-5.20]; for PreSD: 2.39 [1.40-4.08]). Similar results were observed in the rehabilitation phase (for PSCI: 2.48 [1.31-4.70]; for PreSD: 3.92 [1.94-7.92]). Conclusions: Our findings suggest that PSCI, as well as PreSD, is possibly associated with the development of poor functional outcome in the acute care phase of ischemic stroke, and this association continues thereafter.

DOI： 10.1159/000524839

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Language：Japanese   Publisher：Societas Neurologica Japonica  

<p>We present a case of a 41-year-old female presenting with recurrence of ischemic stroke on subtherapeutic doses of dabigatran. She had a history of embolic stroke of undetermined sources at the age of 40, and underwent implantable cardiac monitor implantation and had started dabigatran. One year after the first ischemic stroke, she presented with sudden dysarthria and left hemiparesis and was admitted to our hospital. An MRI of the head revealed acute cerebral infarction in the right corona radiata, and an MR angiography revealed right M2 occlusion. Cervical 3D-CTA revealed a protruding structure on the posterior wall of the carotid artery bulb, which was diagnosed as carotid web. She underwent carotid endarterectomy, and the specimen was pathologically confirmed to be vascular malformation due to fibromuscular dysplasia.</p>

DOI： 10.5692/clinicalneurol.cn-001872

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Language：English   Publisher：The Japanese Circulation Society  

DOI： 10.1253/circj.cj-22-0432

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Language：English   Publisher：Japan Atherosclerosis Society  

<p> <b>Aim:</b> Secular trends in the risk of recurrent stroke have been reported in several epidemiological studies worldwide, but this issue has not been investigated in general Japanese populations. We examined the trends in the 5-year risk of recurrent stroke over a half century using community-based prospective data in Japan.</p><p><b>Methods:</b> We established 4 cohort studies in 1961, 1974, 1988, and 2002. To examine the risk of recurrent stroke, participants who developed stroke during a 10-year follow-up period in each cohort were followed-up for 5 years from the date of first onset. A total of 154 (first sub-cohort: 1961-1971), 144 (second sub-cohort: 1974-1984), 172 (third sub-cohort: 1988-1998), and 146 (fourth sub-cohort: 2002-2012) participants from each cohort were enrolled in the present study. The 5-year cumulative risk of recurrent stroke was compared among the sub-cohorts using the Kaplan-Meier method and the age- and sex-adjusted Cox proportional hazards model.</p><p><b>Results:</b> The risks of recurrent stroke after any stroke and ischemic stroke decreased significantly from the first to the third sub-cohort, but they did not clearly change from the third to the fourth sub-cohort. The risk of recurrent stroke after hemorrhagic stroke decreased mainly from the first to the second sub-cohort and there was no apparent decrease from the second to the fourth sub-cohort. These trends were substantially unchanged after adjusting for age and sex.</p><p><b>Conclusions:</b> In the Japanese community, the risk of recurrent stroke decreased mainly from the 1960s to 1990s, but there was no apparent decrease in recent years.</p>

DOI： 10.5551/jat.63344

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Language：English   Publisher：(一社)日本動脈硬化学会  

一般日本人集団の前向き追跡データを用いて、再発性脳卒中の5年リスクにみられる傾向を半世紀にわたり検討した。福岡県久山町の住民を対象に、1961年から続けられている久山町研究のデータを利用した。1961年(154名)、1974年(144名)、1988年(172名)、2002年(146名)を起点とする四つのコホートを設定し、脳卒中発症患者を起点から10年間追跡したデータを用いて再発性脳卒中リスクを調査した。全種類の脳卒中および虚血性脳卒中を発症した後の再発性脳卒中リスクは、一番目(1961年)のコホートから三番目のコホートにかけて有意に低下していたが、三番目から四番目のコホートでは明瞭な変化は示されなかった。出血性脳卒中後の同リスクは主として一番目から二番目のコホートにかけて低下しており、二番目から四番目まででは明らかな低下はみられなかった。こうした傾向は年齢・性別で調整しても実質的に不変であった。

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：Communications Biology  

Antidiabetic sodium-glucose cotransporter 2 (SGLT2) inhibitors have attracted attention for their cardiorenal-protective properties beyond their glucose-lowering effect. However, their benefits in ischemic stroke remain controversial. Here we show the effects of luseogliflozin, a selective SGLT2 inhibitor, in acute ischemic stroke, using a permanent middle cerebral artery occlusion (pMCAO) model in non-diabetic mice. Pretreatment with low-dose luseogliflozin, which does not affect blood glucose levels, significantly attenuated infarct volume, blood-brain barrier disruption, and motor dysfunction after pMCAO. SGLT2 was expressed predominantly in brain pericytes and was upregulated in peri- and intra-infarct areas. Notably, luseogliflozin pretreatment reduced pericyte loss in ischemic areas. In cultured pericytes, luseogliflozin activated AMP-activated protein kinase α and increased mitochondrial transcription factor A expression and number of mitochondria, conferring resistance to oxygen-glucose deprivation. Collectively, pre-stroke inhibition of SGLT2 induces ischemic tolerance in brain pericytes independent of the glucose-lowering effect, contributing to the attenuation of ischemic brain injury.

DOI： 10.1038/s42003-022-03605-4

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Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：PLoS ONE  

Background Very few comparative studies have focused on the differences in the causes of ischemic stroke between young adults and non-young adults. This study was performed to determine what causes of ischemic stroke are more important in young adults than in non-young adults using a large-scale multicenter hospital-based stroke registry in Fukuoka, Japan. Methods and results We investigated data on 15,860 consecutive patients aged ≥18 years with acute ischemic stroke (mean age: 73.5 ± 12.4 years, 58.2% men) who were hospitalized between 2007 and 2019. In total, 779 patients were categorized as young adults (≤50 years of age). Although vascular risk factors, including hypertension, diabetes mellitus, and dyslipidemia, were less frequent in young adults than in non-young adults, the prevalence of diabetes mellitus and dyslipidemia in young adults aged >40 years were comparable to those of non-young adults. Lifestyle-related risk factors such as smoking, drinking, and obesity were more frequent in young adults than in non-young adults. As young adults became older, the proportions of cardioembolism and stroke of other determined etiologies decreased, but those of large-artery atherosclerosis and small-vessel occlusion increased. Some embolic sources (high-risk sources: arterial myxoma, dilated cardiomyopathy, and intracardiac thrombus; medium-risk sources: atrial septal defect, nonbacterial thrombotic endocarditis, patent foramen ovale, and left ventricular hypokinesis) and uncommon causes (vascular diseases: reversible cerebral vasoconstriction syndrome, moyamoya disease, other vascular causes, arterial dissection, and cerebral venous thrombosis; hematologic diseases: antiphospholipid syndrome and protein S deficiency) were more prevalent in young adults than in non-young adults, and these trends decreased with age. Conclusions Certain embolic sources and uncommon causes may be etiologically important causes of ischemic stroke in young adults. However, the contribution of conventional vascular risk factors and lifestyle-related risk factors is not negligible with advancing age, even in young adults.

DOI： 10.1371/journal.pone.0268481

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Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：Journal of Stroke and Cerebrovascular Diseases  

We report a case of a 59-year-old man with human immunodeficiency virus (HIV)/ acquired immunodeficiency syndrome (AIDS) who developed multiple small-vessel strokes during the immune reconstitution phase. The patient had been diagnosed with HIV/AIDS with a low CD4 count and high viral load and started combinational antiretroviral therapy (cART) with raltegravir, emtricitabine, and tenofovir alafenamide fumarate seven months before the admission. He was admitted to our hospital with complaints of mild dysarthria and left-sided hemiparesis, but lacking consciousness/cognitive disturbances. Diffusion-weighted images (DWI) revealed multiple areas of hyperintensity in the anterior circulation system of the brain. Because we identified decreased activity of protein S through extensive examinations, we treated him initially with intravenous infusion of heparin sodium and aspirin; however, DWI detected multiple progressive small-vessel strokes after that. We considered that the immune reconstitution accounted for the small-vessel vasculopathy/vasculitis, leading to ischemic stroke. Therefore, we initiated oral administration of prednisolone, which successfully prevented stroke recurrence. This report describes a case of multiple small-vessel strokes following cART for AIDS during the immune reconstitution phase, effectively treated with steroids, which may often go undiagnosed due to their relatively mild symptoms.

DOI： 10.1016/j.jstrokecerebrovasdis.2022.106409

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Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：Stroke  

Background and Purpose: This study aimed to determine whether variability of day-by-day blood pressure (BP) during the subacute stage of acute ischemic stroke is predictive of long-term stroke recurrence. Methods: We analyzed 7665 patients (mean±SD age: 72.9±13.1 years; women: 42.4%) hospitalized for first-ever ischemic stroke in 7 stroke centers in Fukuoka, Japan, from June 2007 to November 2018. BP was measured daily during the subacute stage (4-10 days after onset). Its mean and coefficient of variation (CV) values were calculated and divided into 4 groups according to the quartiles of these BP parameters. Patients were prospectively followed up for recurrent stroke or all-cause death. The cumulative event rate was calculated with the Kaplan-Meier method. We estimated the hazard ratios and 95% confidence intervals of the events of interest after adjusting for potential confounders and mean BP values using Cox proportional hazards models. The Fine-Gray model was also used to account for the competing risk of death. Results: With a mean (±SD) follow-up duration of 3.9±3.2 years, the rates of recurrent stroke and all-cause death were 3.9 and 9.9 per 100 patient-years, respectively. The cumulative event rates of recurrent stroke and all-cause death increased with increasing CVs of systolic BP and diastolic BP. The systolic BP CV was significantly associated with an increased risk of recurrent stroke after adjusting for multiple confounders and mean BP (hazard ratio [95% CI] for fourth quartile versus first quartile, 1.26 [1.05-1.50]); the risk of recurrent stroke also increased with an increasing systolic BP CV for nonfatal strokes (1.26 [1.05-1.51]) and when death was regarded as a competing risk (1.21 [1.02-1.45]). Similar associations were observed for the diastolic BP CV. Conclusions: Day-by-day variability of BP during the subacute stage of acute ischemic stroke was associated with an increased long-term risk of recurrent stroke.

DOI： 10.1161/STROKEAHA.120.033751

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Language：English   Publishing type：Research paper (scientific journal)  

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Language：Japanese   Book type：Scholarly book

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Language：Japanese   Book type：Scholarly book

Responsible for pages：急性期脳梗塞モデル 1.動物モデル（げっ歯類） pp177-pp185   Language：Japanese   Book type：Scholarly book

Responsible for pages：虚血性中枢神経障害の基礎と臨床, 牛島一男編, 東京, 真興交易, 2016, pp80-101   Language：Japanese   Book type：Scholarly book

Responsible for pages：虚血性中枢神経障害の基礎と臨床, 牛島一男編, 東京, 真興交易, 2016, pp80-101   Language：Japanese   Book type：Scholarly book

Language：Japanese   Book type：Scholarly book

Event date： 2021.7

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡市   Country：Japan  

Event date： 2021.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡   Country：Japan  

Event date： 2021.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡   Country：Japan  

Event date： 2021.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡   Country：Japan  

Event date： 2021.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：Web上   Country：Japan  

Event date： 2021.2

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡   Country：Japan  

Event date： 2020.12

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：Web上   Country：Japan  

Event date： 2020.11

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：Web上   Country：Japan  

Event date： 2020.10

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡   Country：Japan  

Event date： 2020.9

Language：Japanese  

Venue：Web上   Country：Japan  

Event date： 2020.7

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：Web上   Country：Japan  

Event date： 2020.2

Language：Japanese   Presentation type：Oral presentation (invited, special)  

Venue：都城   Country：Japan  

Event date： 2020.1

Language：Japanese   Presentation type：Oral presentation (invited, special)  

Venue：佐世保   Country：Japan  

Event date： 2019.12

Language：Japanese   Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 2019.10

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡   Country：Japan  

Event date： 2019.9

Language：Japanese   Presentation type：Oral presentation (invited, special)  

Venue：福岡   Country：Japan  

Event date： 2019.8

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡   Country：Japan  

Event date： 2019.4

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡   Country：Japan  

Event date： 2019.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡   Country：Japan  

Event date： 2018.6

Language：English   Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 2018.6

Language：Japanese   Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 2017.11

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：徳島市   Country：Japan  

Event date： 2017.6

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡   Country：Japan  

Event date： 2017.1

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：東京   Country：Japan  

Event date： 2016.5

Language：English   Presentation type：Oral presentation (general)  

Venue：LA, USA   Country：Japan  

Event date： 2016.5

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：横浜   Country：Japan  

Event date： 2016.5

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡市   Country：Japan  

Event date： 2016.5

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：青森市   Country：Japan  

Event date： 2015.10 - 2016.10

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡市   Country：Japan  

Language：Japanese  

Country：Japan  

背景：終末糖化産物受容体への新規リガンドであるS100A12は炎症性サイトカイン発現を亢進させ心血管病の進展に関与することが示唆されている。炎症性サイトカインは脳梗塞機能予後に相関するがS100A12と脳梗塞の関連は不明である。
目的：脳梗塞機能予後とS100A12の関連を検討する。
方法：福岡脳卒中データベース研究の関連3施設での発症24時間以内の脳梗塞171例 (アテローム血栓性34例、心原性脳塞栓49例、ラクナ45例、分類不能43例)に対し、発症日、第3、7、14、90病日に静脈採血を行った。年齢・性をマッチさせた福岡県久山町在住の健常者171例をコントロールとし、背景因子や血液データの解析を行った。
結果：全脳梗塞患者の発症時血漿S100A12は健常者より有意に高値(1.6 [0.8-3.5] vs 0.9 [0.4-1.6] ng/mL, median [IQR], p＜0.001)であった。90日後の予後不良群(mRS:2-6, n=74)は予後良好群(mRS:0-1, n=97)と比較して発症時S100A12が有意に高値(2.1 [1.2-5.3] vs 1.1 [0.5-2.0], p＜0.001)であり、予後不良群は予後良好群と比較して入院時から14病日までS100A12が有意に高値であった。年齢・性・既知の予後不良因子(NIHSS等)を調整したロジスティック回帰分析の結果、発症時S100A12の四分位別の予後不良のオッズ比は、S100A12の増加と共に有意な上昇トレンドを認め(p for trend=0.004)、第3分位群は4.07、第4四分位群は4.60と有意に高値であった。また神経症状改善(第14病日までにNIHSSが4点以上低下またはNIHSS=0)のオッズ比はS100A12の増加と共に有意な下降トレンドを認め(p for trend=0.02)、第3分位群で0.31、第4分位群で0.24と有意に低下していた。
結語：発症時血漿S100A12高値は機能予後不良を予測する独立した因子である可能性がある。

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：札幌   Country：Japan  

【背景】アポリポ蛋白A (ApoA)-1はHDLコレステロールの主要な構成蛋白であり、抗炎症作用・抗酸化作用・血管内皮保護作用を有している。Apo-A1高値は虚血性心疾患の発症抑制や発症後の心血管イベント発症抑制に関与することが示唆されている。一方でApoA-1低値は脳梗塞発症の危険因子であることが報告されているが、ApoA-1と脳梗塞の機能予後との関連は不明である。
【目的】血漿ApoA-1値と脳梗塞発症90日後の機能予後との関連を検討する。
【方法】福岡脳卒中データベース研究の関連3施設での発症24時間以内の脳梗塞171例 (アテローム血栓性34例、心原性脳塞栓49例、ラクナ45例、分類不能43例)に対し、発症日、第3、7、14、90病日に静脈血を採取した。年齢・性をマッチさせた福岡県久山町在住の健常者171例を対照とし、血漿ApoA-1値と脳梗塞機能予後との関連について背景因子を勘案して検討した。
【結果】脳梗塞患者の発症日の血漿ApoA-1値は健常者と比べ有意に低値であった(29.0 [22.0-37.0] vs 34.4 [27.3-45.1] mg/dL, 中央値[IQR], p＜0.0001)。90日後の予後良好群(mRS:0-1, n=97)は予後不良群(mRS:2-6, n=74)と比較して、発症日(31.0 [22.6-39.0] vs 27.0 [19.9-33.6], p=0.03)から発症90日目まで血漿ApoA-1値が有意に高値であった。発症日の血漿ApoA-1値を三分位別に分けて予後良好者の割合を比較すると、第1、第2、第3分位群でそれぞれ50.0%、51.8%、68.4%と血漿ApoA-1値の増加と共に有意に予後良好者の割合が増加した（p for trend=0.04）。また年齢・性・既知の予後関連因子(NIHSS、臨床病型等)を調整したロジスティック回帰分析においても結果は同様であり (p for trend=0.001)、第1分位を基準とした第3分位の予後良好のオッズ比は有意に高値(オッズ比, 6.3; 95% CI, 2.00-22.5; p=0.001)であった。
【結語】発症日の血漿ApoA-1高値は脳梗塞の機能予後良好に対する有意な独立した因子であった。

Language：English   Presentation type：Oral presentation (general)  

Country：United Kingdom  

Language：Japanese   Presentation type：Oral presentation (general)  

Country：Japan  

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡   Country：Japan  

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡   Country：Japan  

Language：Japanese   Presentation type：Oral presentation (general)  

Country：Japan  

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡市   Country：Japan  

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡市   Country：Japan  

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：東京   Country：Japan  

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡   Country：Japan  

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡市   Country：Japan  

Language：Japanese  

Language：English  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

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Language：Japanese  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：English   Publisher：(一社)日本循環器学会  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publisher：(株)ライフメディコム  

日本人の脳梗塞患者で頸動脈病変の有病率に関する報告はほぼない。そこで日本人の急性期脳梗塞患者を対象とした多施設共同前向き登録研究のFukuoka Stroke Registry(FSR)のデータを用いて、日本人の急性期脳梗塞患者13,166例での頸部主幹動脈の狭窄および閉塞病変の有病率について検討した。その結果、総頸動脈・内頸動脈(頭蓋内または頭蓋外)・椎骨動脈(頭蓋内または頭蓋外)・脳底動脈のいずれかに狭窄率中等度以上の狭窄病変または閉塞病変を全脳梗塞患者の24.4%に認めた。脳梗塞臨床病型別での検討では各主幹動脈に中等度以上狭窄や閉塞病変を認めても、半数以上が非アテローム血栓性脳梗塞の症例であった。そのため頸部主幹動脈に狭窄率中等度以上の狭窄病変または閉塞病変を有するとしても、アテローム血栓性脳梗塞以外の臨床病型の脳梗塞を発症している可能性が十分にあることを念頭に置く必要がある。(著者抄録)

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publisher：(株)ライフメディコム  

脳梗塞は年間再発率が5%と再発リスクの高い疾患のひとつであり、再発予防を行うことは非常に重要である。再発予防は大きく分けて、脳梗塞危険因子の管理、抗血栓療法、外科的血行再建療法の3つに分類される。脳梗塞危険因子には、高血圧症、脂質異常症、糖尿病のほかに、肥満症・メタボリックシンドロームや喫煙といった生活習慣が挙げられる。これらはそれぞれ独立した脳梗塞危険因子ではなく、相関関係にあることを意識して診療を行うことが重要である。ただ、脳梗塞再発予防において、カルシウム拮抗薬、アンジオテンシン変換酵素(ACE)阻害薬、アンジオテンシン受容体拮抗薬(ARB)および利尿薬による130/80mmHg未満を目標とした降圧治療以外に、エビデンスの確立した治療法は少ないのが現状であり、今後さらなる研究が望まれる。(著者抄録)

Language：Japanese   Publisher：大道学館出版部  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Internal/External technical report, pre-print, etc.  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Book review, literature introduction, etc.  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Type：Peer review 

Number of peer-reviewed articles in foreign language journals：19

Type：Peer review 

Number of peer-reviewed articles in foreign language journals：13

Type：Peer review 

Number of peer-reviewed articles in foreign language journals：10

Type：Competition, symposium, etc. 

Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

Type：Lecture

日本内科学会JMECC(内科救急・ICLS講習会）においてインストラクターの任を担当し、受講生またアシスタントインストラクターを指導した（2018/11/22)

日本内科学会JMECC(内科救急・ICLS講習会）においてインストラクターの任を担当し、受講生またアシスタントインストラクターを指導した（2016/6/5、2017/1/15)

Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

Type：Seminar, workshop

Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

Type：Lecture