Language：English   Publisher：Nature Publishing Group  

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

The aim of this study was to determine whether pulse pressure (PP), an indicator of arterial stiffness, was independently associated with the risk of acute kidney injury (AKI) following intracerebral hemorrhage (ICH). We enrolled patients with acute ICH from a multicenter stroke registry in Fukuoka, Japan, from June 2007 to September 2019. The mean PP, measured three times on the third day after admission, was categorized into three groups based on tertiles: G1 < 54 mmHg, G2 54-64 mmHg, and G3 ≥ 65 mmHg. AKI was defined as an increase of ≥0.3 mg/dL or ≥150% in serum creatinine levels above baseline during hospitalization. The associations between PP and AKI were evaluated using logistic regression analyses. Overall, 1512 patients with acute ICH (mean age: 69.8 ± 13.5 years; 56.4% men) were included in the analysis. The incidence rates of AKI were 5.6%, 11.0%, and 13.2% in groups G1, G2, and G3, respectively. The odds ratio (95% confidence interval) of AKI was significantly elevated in G2 (1.77 [1.07-2.91]) and G3 (1.82 [1.10-3.03]) compared to G1, even after adjusting for initial systolic blood pressure (SBP) values on admission and subsequent SBP reductions. This significant association was observed in patients with an initial SBP < 200 mmHg (P for heterogeneity, 0.045) and those receiving intravenous antihypertensive therapy in the acute stage (P for heterogeneity, 0.03). High PP should be recognized as a novel potential risk factor for AKI following ICH. High pulse pressure was significantly associated with an increased risk of acute kidneyinjury following intracranial hemorrhage. Pulse pressure should be recognized as anovel potential risk factor and one of the predictors of acute kidney injury afterintracranial hemorrhage.

DOI： 10.1038/s41440-024-02046-2

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

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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Other Link： https://www.nature.com/articles/s41598-024-59508-3

Language：Japanese   Publisher：(一社)日本脳卒中学会  

症例は90歳女性.心房細動に対して,アピキサバンを内服していた.意識障害と右片麻痺のため搬送され,頭部MRIで左後大脳動脈閉塞と同領域に急性期脳梗塞を認めた.大動脈精査の造影CT検査で,右大動脈弓,異所性左鎖骨下動脈に伴うKommerell憩室を認め,憩室内に血栓が示唆される造影欠損を認めた.アピキサバン内服中だったため,Kommerell憩室内の血栓による脳梗塞の可能性が高いと判断した.Kommerell憩室は大動脈弓発生過程での先天性奇形であり,合併症の頻度が高い.また,右大動脈弓を合併することが多く,右大動脈弓の精査から偶然見つかることが多いが,本症例は90歳まで未指摘だった.Kommerell憩室の脳合併症は,破裂や解離によることは想定されるが,Kommerell憩室内血栓で脳梗塞を来した報告は調べた限りなく,稀な1例を経験したため報告する.(著者抄録)

Language：Japanese   Publisher：(一社)日本脳循環代謝学会  

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Language：Japanese   Publisher：(一社)日本脳循環代謝学会  

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Language：Japanese   Publisher：(一社)日本脳循環代謝学会  

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Language：Japanese   Publisher：(一社)日本脳循環代謝学会  

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Language：Japanese   Publisher：(一社)日本脳循環代謝学会  

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Language：English   Publishing type：Research paper (scientific journal)   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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Publishing type：Research paper (scientific journal)   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：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：The Japan Stroke Society  

<p>A 90-year-old woman, being treated with apixaban for chronic atrial fibrillation, was transferred to our hospital with consciousness disturbance and right hemiplegia. Head MRI/A revealed acute cerebral infarction in the whole territory of the left posterior cerebral artery and occlusion at the P1 segment of the artery. Chest roentgenogram showed the right-sided aortic arch and the following contrast-enhanced CT revealed a Kommerell’s diverticulum (KD) complicated with aberrant left subclavian artery. From the filling defect in the diverticulum, we suspected that the thrombus in the KD was the cause of the embolic cerebral infarction. KD is a congenital malformation formed in the process of aortic arch formation and is often found incidentally when searching concomitant anomaly of the right-sided aortic arch. When KD causes symptoms due to its expansion and compression to adjacent organs, it eventually leads to fatal complications, rupture or dissection, and swift surgical repair is recommended. Although cerebral complications may occur secondary to rupture or dissection, ischemic stroke due to thrombus in the KD has not been reported. We present a very rare case of high-aged cerebral infarction caused by KD and treated with another direct oral anticoagulant, rivaroxaban.</p>

DOI： 10.3995/jstroke.11143

CiNii Research

Language：Others   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

The transmembrane protein p22phox heterodimerizes with NADPH oxidase (Nox) 1–4 and is essential for the reactive oxygen species-producing capacity of oxidases. Missense mutations in the p22phox gene prevent the formation of phagocytic Nox2-based oxidase, which contributes to host defense. This results in chronic granulomatous disease (CGD), a severe primary immunodeficiency syndrome. In this study, we characterized missense mutations in p22phox (L51Q, L52P, E53V, and P55R) in the A22° type (wherein the p22phox protein is undetectable) of CGD. We demonstrated that these substitutions enhanced the degradation of the p22phox protein in the endoplasmic reticulum (ER) and the binding of p22phox to Derlin-1, a key component of ER-associated degradation (ERAD). Therefore, the L51-L52-E53-P55 sequence is responsible for protein stability in the ER. We observed that the oxidation of the thiol group of Cys-50, which is adjacent to the L51-L52-E53-P55 sequence, suppressed p22phox degradation. However, the suppression effect was markedly attenuated by the serine substitution of Cys-50. Blocking the free thiol of Cys-50 by alkylation or C50S substitution promoted the association of p22phox with Derlin-1. Derlin-1 depletion partially suppressed the degradation of p22phox mutant proteins. Furthermore, heterodimerization with p22phox (C50S) induced rapid degradation of not only Nox2 but also nonphagocytic Nox4 protein, which is responsible for redox signaling. Thus, the redox-sensitive Cys-50 appears to determine whether p22phox becomes a target for degradation by the ERAD system through its interaction with Derlin-1.

DOI： 10.1016/j.redox.2022.102479

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Language：Japanese   Publisher：(一社)日本脳循環代謝学会  

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Language：Japanese   Publisher：(一社)日本脳循環代謝学会  

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

DOI： 10.1038/s41440-022-00907-2

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

NADPH oxidase (Nox) 4 produces H2O2 by forming a heterodimer with p22phox and is involved in hemangioendothelioma development through monocyte chemoattractant protein-1 (MCP-1) upregulation. Here, we show that Nox4 protein levels were maintained by p22phox in hemangioendothelioma cells and Nox4 protein stability was dependent on p22phox coexpression. Conversely, the degradation of Nox4 monomer was enhanced by p22phox knockdown. Under hypoxic conditions in hemangioendothelioma cells, p22phox was downregulated at the mRNA and protein levels. Downregulation of p22phox protein resulted in the enhanced degradation of Nox4 protein in hypoxia-treated hemangioendothelioma cells. In contrast, Nox2, a Nox isoform, was not altered at the protein level under hypoxic conditions. Nox2 exhibited a higher affinity for p22phox compared with Nox4, suggesting that when coexpressed with Nox4 in the same cells, Nox2 acts as a competitor. Nox2 knockdown restored Nox4 protein levels partially reduced by hypoxic treatment. Thus, Nox4 protein levels were attenuated in hypoxia-treated cells resulting from p22phox depletion. MCP-1 secretion was decreased concurrently with hypoxia-induced Nox4 downregulation compared with that under normoxia.

DOI： 10.1080/10715762.2021.2009116

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

DOI： 10.1080/10715762.2020.1823383

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

DOI： 10.1074/jbc.RA120.014723

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

DOI： 10.1016/j.jstrokecerebrovasdis.2019.05.024

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

We describe the case of a 51-year-old Japanese man with an end-stage kidney disease caused by a 30-year history of type 1 diabetes mellitus. The patient had suffered repeated bilateral multiple brain infarctions within a short period of time after the initiation of a self-managed daily home hemodialysis regimen using a long-term indwelling catheter inserted into the right atrium. Despite extensive examinations, we could not find any embolic causes except for the catheter and a patent foramen ovale (PFO). The patient had experienced repeated brain infarctions under antiplatelet and anticoagulation therapies, but suffered no further brain infarctions after the removal of the catheter and the alteration of vascular access from the catheter to an arteriovenous fistula in the forearm. We speculate that the indwelling catheter-associated thrombi or air and the right-to-left shunt through the PFO may have caused the repeated paradoxical brain embolisms in this patient.

DOI： 10.1016/j.jstrokecerebrovasdis.2017.06.004

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

DOI： 10.1074/jbc.m114.581785

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