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Background: This study aimed to evaluate the efficacy and safety of off-label use of non-vitamin K antagonist oral anticoagulants (NOACs) compared with antiplatelet therapy (APT) in patients with AF-related acute ischemic stroke (AIS) and a glomerular filtration rate (GFR) below 15 mL/min/1.73 m2. Methods: We used a multicenter prospective stroke registry to identify patients with AF-related AIS and GFR < 15 mL/min/1.73 m2 who were treated with either APT alone or NOAC alone at discharge. Primary outcomes were ischemic stroke recurrence, major bleeding, and all-cause mortality within one year. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression. Results: Among 311 eligible patients, 135 (43.4%) received APT and 176 (56.6%) received low-dose NOACs. Compared to APT, NOAC use was associated with a significantly lower risk of ischemic stroke recurrence (aHR 0.54, 95% CI 0.29–0.99) but higher risks of major bleeding (aHR 3.25, 95% CI 1.84–5.73) and all-cause mortality (aHR 2.65, 95% CI 1.60–4.38). The most common causes of death were non-vascular events such as sepsis and respiratory failure. Conclusions: In patients with AF-related stroke and ultra-low GFR, off-label use of NOACs may offer a benefit in stroke prevention but is associated with increased risks of bleeding and mortality. These findings suggest the need for individualized treatment strategies and careful monitoring when prescribing NOACs in this vulnerable population.

Background: Our study aimed to evaluate the impact of EVT on stroke outcomes in patients with LVO with a National Institute of Health Stroke Scale (NIHSS) score of ≤5, exhibiting primarily cortical signs. Methods: We conducted a multicenter registry-based analysis of patients with acute ischemic stroke with LVO who arrived within 12 h of onset. Among these, patients with low NIHSS scores and prominent cortical signs (Items 2, 3, 9, or 11) were included. Patients were divided into two groups: those who underwent EVT and those treated with the best medical therapy (BMT), which included intravenous thrombolysis where appropriate. The primary outcome measure was a modified Rankin scale (mRS) score of 0–1 at 3 months and symptomatic hemorrhagic transformation (SHT). We performed logistic regression analysis to evaluate the impact of EVT on the outcomes. Results: Of the 970 patients with LVO, 291 met the inclusion criteria, with 95 and 196 undergoing EVT and BMT, respectively. The EVT group demonstrated a significantly higher rate of 3-month mRS score of 0–1 (65.3% vs. 39.3%, p < 0.001) and a lower incidence of SHT than the BMT group (3.2% vs. 12.8%, p = 0.01). Multivariate analysis confirmed that EVT was associated with improved functional recovery (mRS score, 0–1; odds ratio [OR], 3.61; 95% confidence interval [CI], 1.82–7.06; p < 0.001) and reduced risk of SHT (OR, 0.19; 95% CI, 0.05–0.74; p = 0.02). Notably, patients with specific cortical signs, such as aphasia and spatial neglect, exhibited better outcomes with EVT. Conclusions: EVT may significantly improve the functional outcomes in patients with mild LVO stroke who present with cortical signs, despite low NIHSS scores. These findings suggest that cortical signs should be a key factor in EVT decision-making for mild stroke cases, thereby advocating for a more individualized approach in acute stroke management.

This study evaluated the potential of iron oxide nanoparticle-loaded human embryonic stem cell (ESC)-derived spherical neural masses (SNMs) to improve the transportation of stem cells to the brain, ameliorate brain damage from intracerebral hemorrhage (ICH), and recover the functional status after ICH under an external magnetic field of a magnet attached to a helmet. At 24 h after induction of ICH, rats were randomly separated into three experimental groups: ICH with injection of phosphate-buffered saline (PBS group), ICH with intravenous injection of magnetosome-like ferrimagnetic iron oxide nanocubes (FION)-labeled SNMs (SNMs* group), and ICH with intravenous injection of FION-labeled SNMs followed by three days of external magnetic field exposure for targeted delivery by a magnet-embedded helmet (SNMs*+Helmet group). On day 3 after ICH induction, an increased Prussian blue-stained area and decreased swelling volume were observed in the SNMs*+Helmet group compared with that of the other groups. A significantly decreased recruitment of macrophages and neutrophils and a downregulation of pro-inflammatory cytokines followed by improved neurological function three days after ICH were observed in the SNMs*+Helmet group. Hemispheric atrophy at six weeks after ICH was significantly decreased in the SNMs*+Helmet group compared with that of the PBS group. In conclusion, we have developed a targeted delivery system using FION tagged to stem cells and a magnet-embedded helmet. The targeted delivery of SNMs might have the potential for developing novel therapeutic strategies for ICH.

Objectives We evaluated the impact of malnutrition as estimated by the controlling nutritional status (CONUT) score and prognostic nutritional index (PNI) on hemorrhagic transformation (HT) and stroke outcomes after intravenous thrombolysis (IVT). Materials and methods Using a multicenter registry database, we enrolled 808 patients with acute ischemic stroke who received IVT between August 2013 and May 2021. We defined malnutrition as a CONUT score ≥ 2 and low PNI. The primary outcome measure was the occurrence of symptomatic HT contributing to early neurologic deterioration (END-SHT) after IVT. Multivariable analysis was performed to analyze the association between CONUT score, PNI, and END-SHT after IVT. Results The rate of END-SHT was higher with increasing CONUT scores and PNI values. In the multivariable analysis, CONUT score ≥ 5 and low PNI were significantly associated with END-SHT (odds ratio [95% confidence interval], CONUT score ≥ 5: 12.23 [2.41–62.07], p = 0.003; low PNI: 4.98 [1.76–14.09], p = 0.003). The receiver operating characteristic curve showed that both the CONUT score and PNI had good predictive ability. The cutoff values for CONUT and PNI were 5 and 42.3, respectively, for END-SHT. Conclusion Malnutrition, as denoted by a higher CONUT score and lower PNI, was associated with END-SHT. The joint application of both nutritional markers could be useful in predicting END-SHT after IVT.

Background Currently, there is a relative lack of detailed reports regarding clinical presentation and outcome of idiopathic intracranial hypertension in Asians. This study aims to describe the clinical features and treatment outcomes of Korean patients with idiopathic intracranial hypertension. Methods We prospectively recruited patients with idiopathic intracranial hypertension from one hospital and retrospectively analyzed the medical records of 11 hospitals in Korea. We collected data regarding preceding medical conditions or suspected medication exposure, headache phenotypes, other associated symptoms, detailed neuroimaging findings, treatments, and outcomes after 1–2 and 3–6 months of treatment. Results Fifty-nine (83.1% women) patients were included. The mean body mass index was 29.11 (standard deviation, 5.87) kg/m 2 ; only 27 patients (45.8%) had a body mass index of ≥ 30 kg/m 2 . Fifty-one (86.4%) patients experienced headaches, patterns of which included chronic migraine (15/51 [29.4%]), episodic migraine (8/51 [15.7%]), probable migraine (4/51 [7.8%]), chronic tension-type headache (3/51 [5.9%]), episodic tension-type headache (2/51 [3.9%]), probable tension-type headache (2/51 [3.9%]), and unclassified (17/51 [33.3%]). Medication overuse headache was diagnosed in 4/51 (7.8%) patients. After 3–6 months of treatment, the intracranial pressure normalized in 8/32 (25.0%), improved in 17/32 (53.1%), no changed in 7/32 (21.9%), and worsened in none. Over the same period, headaches remitted or significantly improved by more than 50% in 24/39 patients (61.5%), improved less than 50% in 9/39 (23.1%), and persisted or worsened in 6/39 (15.4%) patients. Conclusion Our findings suggest that the features of Asian patients with idiopathic intracranial hypertension may be atypical (i.e., less likely obese, less female predominance). A wide spectrum of headache phenotypes was observed. Medical treatment resulted in overall favorable short-term outcomes; however, the headaches did not improve in a small proportion of patients.

There is growing interest in the use of new biomarkers such as glycated albumin (GA). In contrast to glycated hemoglobin (HbA1c), GA showed an inverse correlation with prestroke obesity status, but data are limited for ischemic stroke (IS). We explored the association between GA and body mass index (BMI) and investigated inflammatory cytokines to support the academic background. In total, 155 patients with hyperacute IS (HIS) between 2011 and 2019 were included. To identify the association between GA and BMI, patients were divided into four groups according to BMI quartiles. Levels of inflammatory cytokines, including IL-1β, IL-10, IL-6, TNF-α, and TNF-R1, were determined by ELISA using a ProcartaPlex multiplex immunoassay. The mean age of the 155 patients was 68 ± 12 years, and 67.1% were men. The lowest BMI group had higher GA levels (GA 2 T and 3 T = 80%) (p-value=0.017), and these U-shaped associations were maintained only for small vessel occlusion etiology (p-value= 0.004). Plasma IL-10 levels were positively correlated with BMI and showed a U-shaped pattern (p-value= 0.001). GA levels and BMI had U-shaped associations with HIS. IL-10, which acts as a protective cytokine for cardiovascular disease, may play a novel role in this association. Although GA is an emerging favorable clinical marker of cardiovascular outcomes, obesity status should be considered when interpreting these associations. ●In contrast to HbA1c, GA showed an inverse correlation with prestroke obesity status.●We explored the association among GA, BMI and inflammatory cytokines.●Among a total of 155 patients, GA levels and BMI had U-shaped associations.●IL-10, which acts as a protective cytokine, may play a novel role in this association.●Obesity status should be considered when interpreting these associations.

BackgroundWe assessed the influence of prior non-vitamin K antagonist (NOAC) use on stroke outcomes after endovascular treatment (EVT) in patients at a high risk of stroke based on their pre-stroke CHA2DS2-VASc score, and compared them with those who did not use any antithrombotic (NAU) or antiplatelet (APT) agents.MethodsData were collected from a multicenter database comprising consecutive acute ischemic stroke patients who underwent EVT during a span of 103 months. We evaluated pre-stroke CHA2DS2-VASc scores in enrolled patients and measured instances of successful reperfusion and symptomatic hemorrhagic transformation (SHT) following EVT as the main outcome measures.ResultsAmong 12 807 patients with acute ischemic stroke, 3765 (29.4%) had a history of atrial fibrillation. Of these, 418 patients with CHA2DS2-VASc scores ≥2 received EVT alone. The prior NOAC group showed higher successful reperfusion rates compared with the prior NAU and APT groups (p=0.04). Multivariate analysis revealed that prior NOAC use increased the likelihood of successful reperfusion after EVT (OR [95% CI] 2.54 [1.34 to 4.83], p=0.004) and improved stroke outcomes, while the prior APT group did not. Furthermore, the prior NOAC use group was not associated with SHT after EVT. Propensity score matching confirmed these findings.ConclusionPrior use of NOAC is associated with improved outcomes in high-risk stroke patients (pre-stroke CHA2DS2-VASc score ≥2) undergoing EVT.

Background: This study aimed to evaluate the efficacy and safety of anticoagulants (AC) and antiplatelets (APT) in patients with recent small subcortical infarctions (RSSI) and atrial fibrillation (AF). Methods: We utilized a prospective multicenter stroke registry database to identify patients with RSSI with a concurrent diagnosis of AF. Propensity score matching analysis was used to balance baseline differences among the AC-only, APT-only, and their combination groups. The main outcomes of interest were time to occurrence of minor and major bleeding, stroke recurrence, and all-cause mortality. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for each outcome were calculated using the multivariable Cox proportional hazard regression analysis. Results: Of the 404 eligible patients, 28.2% received APT only, 53.0% received AC only, and 18.9% received a combination of both. Notable differences were observed between these groups in terms of the 1-year stroke recurrence (APT, 32.5%; AC, 5.6%; APT + AC, 9.2%) and all-cause mortality (APT, 21.9%; AC, 6.1%; APT + AC, 14.5%), whereas the rates of bleeding events were comparable. The multivariable analysis indicated a significant association of AC alone with reduced risks of severe bleeding, stroke recurrence, and all-cause mortality compared with APT alone (aHR 0.64, 95% CI 0.41–0.98; aHR 0.11, 95% CI 0.06–0.22; aHR 0.22, 95% CI 0.11–0.44, respectively). The combination group showed a reduced risk of stroke recurrence compared to APT alone (aHR 0.19, 95% CI 0.08–0.46). These findings remained consistent with the propensity score-matched analysis. Conclusion: AC showed better clinical outcomes than APT in patients with RSSI and AF. Additionally, combination therapy with AC and APT was associated with a lower risk of stroke recurrence than APT alone. Graphical abstract

Diabetes mellitus (DM) predisposes individuals to vascular injury, leading to poor outcomes after ischemic stroke and symptomatic hemorrhagic transformation (SHT) after thrombolytic and endovascular treatment (EVT). Metformin (MET), an oral antidiabetic drug, has shown potential neuroprotective effects, but its impact on stroke prognosis in DM patients undergoing EVT remains unclear. In a multicenter study, 231 patients with DM undergoing EVT for acute ischemic stroke were enrolled. Prior MET use was identified, and patients were stratified into MET+ and MET− groups. Demographics, clinical data, and outcomes were compared between groups. Multivariate analysis was used to assess the effect of MET on stroke prognosis. Of the enrolled patients, 59.3% were previously on MET. MET+ patients had lower initial infarct volumes and NIHSS scores compared to MET-taking patients. Multivariate analysis showed that MET+ was associated with a lower risk of stroke progression and SHT (with stroke progression as follows: odd ratio [OR] 0.24, 95% confidence interval [CI] [0.12–0.48], p < 0.001; SHT: OR 0.33, 95% CI [0.14–0.75], p = 0.01) and was also associated with better 3-month functional outcomes (mRS 0–2) after EVT. Prestroke MET use in DM patients undergoing EVT is associated with improved stroke prognosis, including reduced risk of stroke progression and SHT and better functional outcomes. These findings suggest the potential neuroprotective role of MET in this population and highlight its clinical utility as an adjunctive therapy in the management of ischemic stroke. Further research is warranted to elucidate the underlying mechanisms and to optimize MET therapy in this setting.

Introduction: We evaluated the effects of prior antiplatelet use (APU) on futile reperfusion (FR) after endovascular treatment (EVT) in acute ischemic stroke. Material and methods: We consecutively collected data of 9369 patients with acute ischemic stroke from four university-affiliated multicenter registry databases over 92 months. We enrolled 528 patients with acute stroke receiving EVT. Among them, we defined FR in subjects as a 3-month modified Rankin Scale score of >2 despite successful reperfusion after EVT. We classified patients into two groups: prior APU and no prior APU. We used propensity score matching (PSM) to overcome the imbalance in multiple covariates between the two groups. After PSM, we compared the baseline characteristics between the two groups and performed multivariate analysis to determine whether prior APU affected FR and other stroke outcomes. Results: The overall FR rate in the present study was 54.2%. In the PSM cohort, the FR was lower in the prior APU group than that in the no prior APU group (66.2% vs 41.5%, p < 0.001). In the multivariate analysis using the PSM cohort, prior APU significantly reduced the risk of FR (odds ratio (OR), 0.32; 95% confidence interval (CI), 0.18–0.55; p = 0.001) and stroke progression (OR, 0.38; 95% CI, 0.15–0.93; p = 0.03). Prior APU was not associated with symptomatic hemorrhagic transformation in this study. Conclusion: Prior APU potentially reduced FR and stroke progression. Further, prior APU was not associated with symptomatic hemorrhagic transformation in patients receiving EVT. APU pretreatment can be a modifiable predictor of FR in clinical practice.