Search

Background: Neutrophils and Lipocalin-2 (LCN2) play pivotal roles in cerebral ischemiareperfusion (I/R) injury. However, their contribution is not fully clarified., Objective: This study aimed to explore the role of LCN2 and its association with neutrophil polarization in I/R injury., Methods: A mouse model of middle cerebral artery occlusion (MCAO) was used to induce cerebral ischemia. LCN2mAb was administered 1 h and Anti-Ly6G was administered for 3d before MCAO. The role of LCN2 in the polarity transition of neutrophils was explored using an in vitro HL-60 cell model., Results: LCN2mAb pretreatment had neuroprotective effects in mice. The expression of Ly6G was not significantly different, but the expression of N2 neutrophils was increased. In the in vitro study, LCN2mAb-treated N1-HL-60 cells induced N2-HL-60 polarization., Conclusion: LCN2 may affect the prognosis of ischemic stroke by mediating neutrophil polarization., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background and Objectives: Evidence on the associations between baseline stromal cell-derived factor (SDF)-1 and clinical outcomes in acute ischemic stroke patients is lacking. The present study aimed to examine the relationship between plasma SDF-1 levels and clinical outcomes based on a large multicenter study of the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS)., Methods: Secondary analysis was conducted among 3,255 participants from the CATIS trial with a baseline measurement of plasma SDF-1 levels. We evaluated the associations between plasma SDF-1 levels and one-year recurrent stroke, cardiovascular events, and all-cause mortality using Cox regression models. We further investigated the prognostic effect of SDF-1 on clinical outcomes in patients with different characteristics., Results: Higher plasma SDF-1 levels were not associated with recurrent stroke, cardiovascular events, and all-cause mortality at one-year after ischemic stroke (all P trend ≥ 0.05). There were significant interactions between plasma SDF-1 levels and history of diabetes mellitus on recurrent stroke (P = 0.005), cardiovascular events (P = 0.007) and all-cause mortality (P = 0.04) at one year. In patients with diabetes mellitus, plasma SDF-1 was significantly associated with an increased risk of recurrent stroke and cardiovascular events after adjustment for confounders. For example, 1-SD higher log-SDF-1 was associated with a hazard ratio (95% confidence interval) of 1.65 (1.18-2.32) for recurrent stroke and 1.47 (1.08-1.99) for the cardiovascular events, but not all-cause mortality 1.36 (0.96-1.93) at one year. However, there were no associations between plasma SDF-1 and clinical outcomes in patients without diabetes mellitus (all P > 0.05). The addition of plasma SDF-1 to the conventional risk factors model significantly improved the risk prediction of all outcomes. Similarly, findings between elevated SDF-1 levels and two-year outcomes were found only in patients with diabetes mellitus., Conclusions: Elevated plasma SDF-1 was significantly associated with an increased risk of recurrent stroke and cardiovascular events only in ischemic patients with diabetes mellitus., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The association between atrial fibrillation (AF) and the prognosis of acute ischaemic stroke (AIS) remains controversial; whether the recombinant tissue plasminogen activator dose influences this association remains poorly understood., Methods: Patients who had an AIS were enrolled from eight stroke centres in China. According to the recombinant tissue plasminogen activator dose, patients treated with intravenous recombinant tissue plasminogen activator within 4.5 hours after symptom onset were divided into a low-dose group (recombinant tissue plasminogen activator <0.85 mg/kg) and a standard-dose group (recombinant tissue plasminogen activator ≥0.85 mg/kg). Patients who had an AIS in the low-dose group and the standard dose group were divided into whether or not they had AF. The main outcomes were major disability (modified Rankin scale (mRS) score 3-5), mortality and vascular events occurring within 3 months., Results: The study included 630 patients who received recombinant tissue plasminogen activator after AIS, including 391 males and 239 females, with a mean age of 65.8 years. Of these patients, 305 (48.4%) received low-dose recombinant tissue plasminogen activator and 325 (51.6%) received standard dose recombinant tissue plasminogen activator. The recombinant tissue plasminogen activator dose significantly influenced the association between AF and death or major disability (p-interaction=0.036). After multivariate adjustment, AF was associated with an increased risk of death or major disability (OR 2.90, 95% CI 1.47 to 5.72, p=0.002), major disability (OR 1.93, 95% CI 1.04 to 3.59, p=0.038) and vascular events (HR 5.01, 95% CI 2.25 to 11.14, p<0.001) within 3 months in patients with standard-dose recombinant tissue plasminogen activator. No significant association was found between AF and any clinical outcome in patients with low-dose recombinant tissue plasminogen activator (all p>0.05). With AF, the mRS score distribution showed a significantly worse shift in patients with standard-dose recombinant tissue plasminogen activator (p=0.016) than in those with low-dose recombinant tissue plasminogen activator (p=0.874)., Conclusions: AF may be a strong predictor of poor prognosis in patients who had an AIS receiving standard-dose recombinant tissue plasminogen activator, suggesting that low-dose recombinant tissue plasminogen activator should be administered to patients who had a stroke with AF to improve their prognosis., (© The Author(s) 2022. Published by Oxford University Press on behalf of Postgraduate Medical Journal. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: We investigated the association between international normalised ratio (INR) and prothrombin time (PT) levels on hospital admission and in-hospital outcomes in acute ischaemic stroke (AIS) patients., Methods: A total of 3175 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included. We divided patients into four groups according to their level of admission INR: (<0.92), Q2 (0.92-0.98), Q3 (0.98-1.04) and Q4 (≥1.04) and PT. Logistic regression models were used to estimate the effect of INR and PT on death or major disability (modified Rankin Scale score (mRS)>3), death and major disability (mRS scores 4-5) separately on discharge in AIS patients., Results: Having an INR level in the highest quartile (Q4) was associated with an increased risk of death or major disability (OR 1.69; 95% CI 1.23 to 2.31; P-trend = 0.001), death (OR, 2.64; 95% CI 1.12 to 6.19; P-trend = 0.002) and major disability on discharge (OR, 1.56; 95% CI 1.13 to 2.15; P-trend = 0.008) in comparison to Q1 after adjusting for potential covariates. Moreover, in multivariable logistic regression models, having a PT level in the highest quartile also significantly increased the risk of death (OR, 2.38; 95% CI 1.06 to 5.32; P-trend = 0.006) but not death or major disability (P-trend = 0.240), major disability (P-trend = 0.606) on discharge., Conclusions: High INR at admission was independently associated with death or major disability, death and major disability at hospital discharge in AIS patients and increased PT was also associated with death at hospital discharge., (© The Author(s) 2022. Published by Oxford University Press on behalf of Postgraduate Medical Journal. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: We aimed to develop and validate a clinical score to identify the factors which contribute to variation in, and influence clinician's decision-making about treating acute ischemic stroke (AIS) patients with Intravenous thrombolysis (IVT)., Methods: We retrospectively included consecutive AIS patients within 4.5 hours after onset in the emergency department (ED), who were admitted to a comprehensive stroke center in Jiangsu province, China. The patients were randomly divided into derivation (60%) and validation data sets (40%) to develop and validate the clinical score. Multivariable stepwise forward logistic regression was performed to identify the independent predictors of IVT offering in the derivation data., Results: Out of 526 included patients, 418 patients received thrombolytic therapy. Nine patient factors were associated with the likelihood of thrombolysis (age, time to hospital, National Institute of Health stroke scale (NIHSS) score, great vessel, facial paralysis, dizziness, headache, history of stroke, and neutrophil ratio). The c-statistics of the Intravenous Thrombolysis Score in the derivation cohort (n= 316) and validation cohort(n = 210) were 0.795 and 0.751, respectively. The performance of the scoring model was validated with a calibration plot showing good predictive accuracy for the scores in the derivation data (calibrated P = 0.861) and validation data (calibrated P = 0.876)., Conclusions: The Intravenous Thrombolysis Score for predicting the possibility of offering IVT to AIS patients indicates that clinicians differ in their thresholds for the treatment across a number of patient-related factors, which will be linked to training professional development programmes and address the impact of non-medical influences on decision-making using evidence-based strategies., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Recent studies have suggested that plasma soluble dipeptidyl peptidase-4 (sDPP4) have important physiologic effects, which may influence the prognosis of ischemic stroke. Our study aimed to examine the relationship between plasma sDDP4 levels and long-term clinical outcomes among patients with acute ischemic stroke., Methods: Secondary analysis was conducted among 3,564 participants (2,270 men and 1,294 women) from the China Antihypertensive Trial in Acute Ischemic Stroke with baseline measurement of plasma sDPP4 levels. We evaluated the associations between plasma sDPP4 levels and 2-year clinical outcomes using logistic regression and Cox regression models. We further investigated the predictive utility of sDPP4 by calculating net reclassification index and integrated discrimination improvement., Results: The highest plasma sDPP4 quartile was associated with lower risk of cardiovascular events (hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.45-0.87), recurrent stroke (HR 0.70, 95% CI 0.49-0.99), all-cause mortality (HR 0.62, 95% CI 0.44-0.87), stroke-specific mortality (HR 0.65, 95% CI 0.44-0.94), and poor functional outcomes (odds ratio 0.66, 95% CI 0.53-0.82) at 2 years compared with the lowest sDPP4 category in multivariable models. The addition of plasma sDPP4 to conventional risk factors model significantly improved risk prediction of all outcomes., Discussion: In this study, we found that higher plasma sDPP4 levels in patients with acute ischemic stroke were associated with decreased risks of cardiovascular events, recurrent stroke, all-cause mortality, and poor functional outcomes after ischemic stroke. These findings suggest that plasma sDPP4 may be a potential prognostic marker for initial risk stratification in patients with acute ischemic stroke., (© 2022 American Academy of Neurology.)

Objective: We compared outcomes and adverse events of thrombectomy versus medical management in acute ischemic stroke (AIS) patients with baseline large infarct core., Methods: We searched Ovid MEDLINE(R) ALL, Cochrane Library Clinical Controlled Trials and EMBASE from inception to January 2021 for studies comparing thrombectomy and medical management alone in AIS patients who had ASPECTS <=7 or ischemic core volume >=50 ml. Imaging modalities to valuate ASPECTS and core volume were without restriction. The functional outcome was measured by mRS (modified Rankin Scale) score 0-2 at 90 days or discharge. The safety end point included the rates of mortality and sICH (symptomatic intracranial hemorrhage) or PH2 (parenchymal hematoma type 2)., Results: Fourteen studies with a total of 2547 patients (thrombectomy n = [1197]; medical care alone [n = 1350]) fulfilled our criteria. As for patients with low ASPECTS, pooled results indicated a higher odds of good functional outcome (OR = 3.47; 95% CI 1.99 to 6.07; P < 0.0001, I 2 =66%) and a lower risk of mortality (OR = 0.62; 95% CI 0.46 to 0.83; P = 0.001, I 2 =32%) in thrombectomy group compared with no thrombectomy group, but the risk of sICH or PH2 did not differ between two groups. As for patients with large core volume, both functional outcome and safety end point between two groups showed no statistically significant difference., Conclusion: Thrombectomy remained safe and effective by careful selection in patients with low ASPECTS. More studies were warranted to explore contraindications for mechanical thrombectomy in AIS patients, especially in patients with large core volume.

Prior studies had reported monocyte to high-density lipoprotein cholesterol ratio (MHR) as a new inflammation marker and stroke-associated pneumonia (SAP) is common after stroke. We investigated the predictive value of MHR for SAP in patients with acute ischemic stroke (AIS). A total of 803 AIS patients within 72 h after stroke were enrolled from April 2012 to January 2016 in Zhangjiagang TCM Hospital affiliated to the Nanjing University of Chinese Medicine. MHR measurement within 24 h of hospital admission was divided into quartiles: Q1 (< 0.21), Q2 (0.21-0.30), Q3 (0.30-0.45), and Q4 (≥ 0.45). Monocyte count was also divided into categories. Clinical outcomes were post-stroke SAP and 3-month mortality. 121 patients (15.1%) experienced SAP during hospitalization, and 109 patients (13.6%) died from all causes within 3 months after AIS. Compared to the lowest quartile, having admission MHR level in the highest quartile was associated with SAP [adjusted odds ratio (aOR) 2.79, 95% confidence interval (CI) 1.44-5.42; P trend = 0.003]. Compared with the lowest category of monocyte, the highest category was associated with a 2.60-fold increase in the odds of SAP (aOR 2.60, 95% CI 1.28-5.30; P trend = 0.005). However, there was no significant association between MHR (P trend = 0.514) and monocyte count (P trend = 0.684) and all-cause mortality at 3 months. We demonstrated that both higher MHR and higher monocyte count at admission predicted SAP in patients with AIS., (© 2020. Belgian Neurological Society.)

Background: Few studies focused on the functional outcomes of patients at 3 months after receiving intravenous thrombolysis, anticoagulation, or antiplatelet therapy within 4.5 h of onset of the cardiogenic cerebral embolism (CCE) subtype., Methods: The purpose of this retrospective study was to analyse the clinical data of patients with acute CCE and compare the 3-month functional prognoses of patients after administration of different antithrombotic therapies within 4.5 h of stroke onset. A total of 335 patients with CCE hospitalized in our institution were included in this study. The patients were stratified according to the hyperacute treatment received, and baseline clinical and laboratory data were analysed. A 3-month modified Rankin scale (mRS) score of 0-2 was defined as an excellent functional outcome., Results: A total of 335 patients were divided into thrombolytic (n = 78), anticoagulant (n = 88), and antiplatelet therapy groups (n = 169). A total of 164 patients had a good prognosis at 3 months (mRS ≤ 2). After adjustments were made for age and National Institute of Health Stroke Scale (NIHSS) score, each group comprised 38 patients, and there were no significant differences in sex composition, complications, lesion characteristics, or Oxfordshire Community Stroke Project (OSCP) classification among the three groups. The plasma D-dimer level (µg/ml) in the thrombolytic group was significantly higher than those in the anticoagulant and antiplatelet groups [3.07 (1.50,5.62), 1.33 (0.95,1.89), 1.61 (0.76,2.96), P < 0.001]. After one week of treatment, the reduction in NIHSS in the thrombolytic group was significantly greater than those in the other two groups [3.00 (1.00, 8.00), 1.00 (0.00, 5.00), 1.00 (0.00, 2.00), P = 0.025]. A total of 47 patients (41.2 %) had an mRS score of ≤ 2 at 3 months, and 23 patients died (20.2 %). There was no significant difference in the proportion of patients with a good prognosis or the mortality rate among the three groups (P = 0.363, P = 0.683)., Conclusions: Thrombolytic therapy is effective at improving short-term and 3-month prognoses. Anticoagulant therapy may be a safe and effective treatment option for patients with the cardiac stroke subtype who fail to receive intravenous recombinant tissue plasminogen activator (r-tPA) thrombolysis within 4.5 h in addition to antiplatelet therapy, as recommended by the guidelines., (© 2021. The Author(s).)

Background: Remnant cholesterol makes great contribution to residual risk of cardiovascular disease, but population-based evidence on the relationship between remnant cholesterol and atherosclerosis is rare. Common carotid artery intima-media thickness (cIMT) is an imaging marker of subclinical atherosclerosis. We aimed to explore the association between remnant cholesterol levels and cIMT in patients with ischemic stroke., Methods: One thousand four hundred ninety-six ischemic stroke patients with baseline serum lipids and carotid artery imaging data were included in this analysis. Fasting remnant cholesterol was calculated as total cholesterol minus HDL (high-density lipoprotein) cholesterol minus LDL (low-density lipoprotein) cholesterol. Abnormal cIMT was defined as mean cIMT and maximum cIMT value ≥1 mm. Logistic regression and restricted cubic spline models were used to assess the relationships between remnant cholesterol levels and abnormal cIMT., Results: The multivariable-adjusted odds ratios (95% CIs) for the highest versus lowest quartile of remnant cholesterol were 2.06 (1.46-2.91) for abnormal mean cIMT and 1.70 (1.23-2.35) for abnormal maximum cIMT. There were linear associations between remnant cholesterol levels and both abnormal mean cIMT ( P for linearity, <0.001) and abnormal maximum cIMT ( P for linearity, 0.003). Moreover, the remnant cholesterol-cIMT association remained significant in the subsample of patients with optimal LDL cholesterol levels (n=179)., Conclusions: Elevated fasting remnant cholesterol levels were positively associated with mean cIMT and maximum cIMT in patients with ischemic stroke, even in patients with optimal LDL cholesterol levels. Future prospective studies are needed to verify our findings and to assess the effect of remnant cholesterol-lowering interventions in patients with ischemic stroke.

Brain-derived neurotrophic factor (BDNF) provides neuroprotective effects towards therapeutic cerebral ischemia-reperfusion (I/R) injury. This view has been proposed by more and more evidence. However, due to the lack of permeability of the blood-brain barrier (BBB) as well as the brief half-life in serum, clinical application is not widespread. To study the participation of exosomes containing BDNF in I/R, we isolated exosomes from BDNF-overexpressing HEK293. The protective outcomes of exosomes in hypoxia/reoxygenation (H/R) experiments were determined by the use of SY-5Y cells. Exosome-BDNF therapy restrained H/R-induced apoptosis by inhibition of the reducing levels of oxidative stress and calcium ions in the cells while maintaining stable levels of mitochondrial membrane potential in brain cells damaged by I/R. We then constructed a cerebral I/R injury model using SD rats to find the function of BDNF in exosome-mediated neuroprotection. The in vivo experiments conducted established that exosomes from BDNF-overexpressing HEK293 cells improved cerebral I/R injury by concealing neuronal apoptosis. Findings gained demonstrated that BDNF is a part of preventing cerebral I/R injury due to exosome mediation by regulating the cellular internal environment and inhibiting apoptosis., Competing Interests: There is no conflict of interest declared in this article., (Copyright © 2021 Lizong Wang et al.)

Background: Previous studies have demonstrated the efficacy of the "drip-and-ship" model in acute ischemic stroke (AIS) patients treated with intravenous (IV) thrombolysis. We investigated and report the outcomes of the safety and efficacy of the "drip-and-ship" model in AIS patients with acute large-vessel occlusion (LVO) in the anterior circulation who underwent endovascular treatment., Methods: A total of 92 AIS patients with LVO who underwent endovascular treatment enrolled from April 2017 to July 2018 at a single academic comprehensive stroke center (CSC) were included. Patients were divided into 2 groups: a front-door group (directly admitted to the CSC) and a drip-and-ship group (transferred to the CSC from other hospital). Logistic regression model was used to evaluate the functional outcome, mortality, and symptomatic intracranial hemorrhage (sICH) at 90 days., Results: After adjusting for age, gender, occlusion site, National Institutes of Health Stroke Scale (NIHSS) score, and other potential covariates, we did not see difference in modified Rankin Scale (mRS) score between the 2 groups at 90 days. The rate of excellent functional outcome (defined as mRS 0-1) in the drip-and-ship group is lower than the front-door group (p = 0.017); however, functional outcomes (defined as mRS 0-2) have no difference (p = 0.117). There was no significant difference in sICH (p = 0.909) and mortality (p = 0.319) between the 2 groups., Conclusions: The "drip-and-ship" model has the potential to be a feasible model for patients with LVO in the anterior circulation to undergo endovascular treatment. Further large-scale prospective studies are warranted to confirm these findings., (© 2021 S. Karger AG, Basel.)

Background: We investigated the combined effect of white blood cell (WBC) and platelet count on in-hospital mortality and pneumonia in acute ischemic stroke (AIS) patients., Methods: A total of 3,265 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included in the present study. We divided patients into four groups according to their level of WBC and platelet count: LWHP (low WBC and high platelet), LWLP (low WBC and low platelet), HWHP (high WBC and high platelet), and HWLP (high WBC and low platelet). A logistic regression model was used to estimate the combined effect of WBC and platelet counts on all-cause in-hospital mortality and pneumonia in AIS patients., Results: HWLP was associated with a 2.07-fold increase in the risk of in-hospital mortality in comparison to LWHP (adjusted odds ratio (OR) 2.07; 95% confidence interval (CI), 1.02-4.18; P-trend =0.020). The risk of pneumonia was significantly higher in patients with HWLP than those with LWHP (adjusted OR 2.29; 95% CI, 1.57-3.35; P-trend <0.001). The C-statistic for the combined WBC and platelet count was higher than WBC count or platelet count alone for the prediction of in- -hospital mortality and pneumonia (all P < 0.01)., Conclusion: High WBC count combined with a low platelet count level at admission was independently associated with in-hospital mortality and pneumonia in AIS patients. Moreover, the combination of WBC count and platelet count level appeared to be a better predictor than WBC count or platelet count alone., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This study aimed to investigate the association between dynamic changes in fibrinogen and the prognosis of acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT). We measured fibrinogen levels at admission and 24 h after IVT in 364 consecutively recruited AIS patients. The primary outcome was the composite measure of death or major disability (modified Rankin Scale score 3-6) at 3 months. During the 3-month follow-up, 127 (34.89%) patients experienced death or major disability. After multivariate adjustment, a ≥ 2.5% increase in fibrinogen was associated with an increased risk of the primary outcome (odds ratio [OR], 2.26; 95% confidence interval [CI] 1.08-4.75; p trend = 0.030) when 2 extreme tertiles were compared. Each 1% increase in fibrinogen after IVT was associated with a 1% increase in the risk of the primary outcome (OR 1.01, 95% CI 1.00-1.03). Multivariable-adjusted spline regression revealed a linear dose-response relationship between fibrinogen changes after IVT and the primary outcome (p for linearity = 0.032). The addition of fibrinogen changes to conventional risk factors improved the re-classification (but not discrimination) of the primary outcome (net reclassification index 27.6%, p = 0.011). These findings indicated that an increase in fibrinogen after IVT was associated with an increased risk of death or major disability in AIS patients, suggesting that monitoring the dynamic profile of fibrinogen levels may help neurologists improve stroke outcomes in clinical settings.

Background: In this study, we developed novel logistic regression models for the diagnostic and prognostic assessment of ischemic stroke., Methods: A total of 288 ischemic stroke patients and 300 controls admitted to The First Affiliated Hospital of Soochow University were included in the testing group. Two validation groups from The Affiliated Kunshan Hospital of Jiangsu University and The Second Affiliated Hospital of Soochow University were included to assess our novel assessment models., Results: Results from the testing group indicated that the diagnostic assessment model for ischemic stroke prediction was: Logit(P) = 437.116 - 87.329 (Hypertension) - 89.700 (Smoking history) - 87.427 (Family history of ischemic stroke) - .090 (high-density lipoprotein cholesterol [HDL-C]) - 1.984 (low-density lipoprotein cholesterol [LDL-C]) - 17.005 (Lp(a)) - 15.486 (Apo A/Apo B), and the final prognostic assessment model of ischemic stroke was: Logit(P) = 458.437-92.343 (Hypertension) - 89.763 (Smoking history) + .251 (NLR) - .088 (HDL-C) - 1.994 (LDL-C) - 2.883 (hs-CRP) - .058 (IL-6) - 6.356 (TNF-α) - 16.485 (Lp(a)) - 17.658 (Apo A/Apo B). In the validation groups, our novel diagnostic assessment model showed good identification (with 87.5% sensitivity and 84.2% specificity in The Affiliated Kunshan Hospital of Jiangsu University, with 85.5% sensitivity and 89.0% specificity in The Second Affiliated Hospital of Soochow University). Moreover, our novel prognostic assessment model has a high value in identifying poor prognosis patients in the validation groups from The Affiliated Kunshan Hospital of Jiangsu University (χ 2  = 8.461, P = .004), and The Second Affiliated Hospital of Soochow University (χ 2  = 7.844, P = .005)., Conclusions: The diagnostic and prognostic assessment models we have established are of great value in the diagnosis and prognostic evaluation of ischemic stroke., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Ischemic stroke refers to brain tissue ischemia, hypoxic necrosis, and brain softening caused by the interruption of the blood supply to the brain without adequate collateral circulation, thus resulting in neurological symptoms. Autophagy is activated in various cell types in the brain, such as neurons, glial cells, and microvascular cells, upon ischemic stroke. Autophagy efflux injury plays an important role in this pathologic process. This chapter outlines the induction of basal autophagy, autophagy in neurons, and the crosstalk between autophagy, necrosis, and apoptosis that contributes to ischemic stroke. We will highlight the interactions between autophagy, oxidative stress, endoplasmic reticulum stress, and mitochondrial dysfunction, and the role of autophagy in ischemic stroke. We will also review the recent advances in the understanding of the involvement of autophagy in the pathological process of cerebral ischemic preconditioning, periconditioning, and postconditioning.

Background: Less is known about the prognostic value of serum cystatin C in acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT). The aim of the present study was to examine the association between serum cystatin C levels and prognosis of AIS patients after IVT., Methods: Serum cystatin C was measured within 24 hours after recombinant tissue plasminogen activator (rt-PA) treatment in 280 consecutively recruited patients with AIS. The main outcomes included combination of death and major disability, death, major disability (modified Rankin Scale score 3-5) and vascular events at 3-month follow-up., Results: During the 3-month follow-up, 94 patients (33.6%) experienced death or major disability (28 deaths and 66 major disability) and 49 patients (17.5%) experienced vascular events. After multivariate adjustment, serum cystatin C was significantly associated with an increased risk of the combined outcome of death and major disability (OR=4.51, P = 0.006). Adding serum cystatin C quartiles to a model containing conventional risk factors improved the predictive power for the combined outcome of death and major disability (continuous net reclassification index 43.88%, P < 0.001; categorical net reclassification index 9.15%, P = 0.013; integrated discrimination improvement 2.31%, P = 0.025). Similar phenomena were also observed in major disability and vascular events., Conclusion: Higher levels of serum cystatin C in AIS patients after IVT were independently associated with increased risks of poor functional outcomes and vascular events, especially combining conventional risk factors, suggesting that serum cystatin C might improve risk prediction for poor prognosis in AIS patients receiving rt-PA treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: We performed a meta-analysis to compare the efficacy and safety between low- and standard-dose intravenous (IV) tissue-type plasminogen activator (tPA) for acute ischemic stroke (AIS) patients within 4.5 hours of symptom onset., Methods: We searched PubMed and EMBASE for relevant studies from inception to June1, 2017. Cohort or randomized controlled studies for AIS within 4.5 hours of symptom onset with comparison between low-dose and standard-dose tPA were included. The primary efficacy end point was favorable functional outcome (modified Rankin scale scores [mRS] of 0-1) at 90 days. The primary safety end point was the incidence rate of symptomatic intracerebral hemorrhage (sICH). The secondary end points were independent functional outcome (mRS scores of 0-2) and mortality., Results: A total of 11 studies were pooled in this meta-analysis. The low-dose strategy appeared to be as effective as standard-dose tPA (43.4% versus 45.4%; odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.78-1.10; P = .38) in primary efficacy outcome. The secondary efficacy outcome produced similar results (57.3% versus 57.0%; OR = 0.95, 95% CI: 0.86-1.05; P= .33). There was no evidence of statistical difference for sICH (4.2% versus 4.9%; OR = 1.02 [0.66-1.55]; P = .94) and mortality (9.0% versus 10.6%; OR = 0.99 [0.74-1.31]; P = .92) at 90 days between low- and standard-dose therapy. In a subgroup analysis by ethnicity, there was no significant difference between patients of Asian and non-Asian descent for any of the end points., Conclusions: This study showed that AIS patients receiving low-dose IV-tPA had comparably efficacy and safety to those receiving standard-dose IV-tPA. However, the effect is especially pronounced within the Asian population, which limits the generalizability of these results., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: The clinical impacts of serum alkaline phosphatase (ALP) and phosphate on early death are not fully understood in patients with acute ischemic stroke. We examined the associations between serum ALP, phosphate, and in-hospital mortality after ischemic stroke., Methods: Serum ALP and phosphate were measured in 2944 ischemic stroke patients from 22 hospitals in Suzhou City from December 2013 to May 2014. Cox proportional hazard models and restricted cubic splines were used to estimate the relationships between serum ALP and phosphate (both as categorical and continuous variables) and risk of in-hospital mortality., Results: During hospitalization, 111 patients (3.7%) died from all causes. After multivariable adjustment, the hazard ratio (HR) of the highest quartile compared with the lowest quartile of ALP was 2.19 (95% confidence interval [CI], 1.20-4.00) for early death. Restricted cubic spline analysis indicated a significant linear association between ALP and death (P-linearity = .017). A U-shaped association of phosphate with in-hospital mortality was observed (P-nonlinearity = .011). Compared with the third quartile of phosphate (1.08-1.21 mmol/L), HRs of the lowest and highest quartiles for early death were 2.17 (1.15-4.08) and 1.70 (.88-3.30), respectively. Sensitivity analyses further confirmed our findings., Conclusions: We observed a graded relationship between serum ALP levels and risk of early death in patients with acute ischemic stroke. There was a U-shaped association between phosphate and all-cause mortality with significantly increased risk among patients with lower phosphate levels., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: The prognostic value of White Blood Cell (WBC) counts and C-reactive Protein (CRP) in clinical outcomes of Acute Ischemic Stroke (AIS) patients after Intravenous Thrombolysis (IVT) remains unknown. We investigated the association of WBC counts and CRP with 3-month functional outcomes and all-cause mortality in AIS patients., Methods: 447 AIS patients treated with IVT between May 2010 and May 2017 were enrolled. WBC counts and CRP were measured within 24 hours after IVT. The main outcomes included poor functional outcomes (modified Rankin score ≥3) at 3 months and 3-month all-cause mortality., Results: High WBC counts were associated with poor functional outcomes (adjusted OR (odds ratio) 4.48; 95% CI (confidence interval) 2.00-10.03; P-trend<0.001) and with all-cause mortality (adjusted HR (hazard ratio) 2.19; 95% CI 1.07-4.49; P-trend=0.018). In addition, high CRP levels were associated with poor functional outcomes (adjusted OR 4.95; 95% CI 1.39-17.65; Ptrend= 0.002). However, no significant association between high CRP levels and all-cause mortality was observed (adjusted HR 2.61; 95% CI 0.80-8.47; P-trend=0.138)., Conclusion: Our analysis indicated that elevated WBC counts and CRP levels after IVT can independently predict poor outcome among AIS patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: The impact of hyperfibrinogenemia on short-term outcomes after acute ischemic stroke (AIS) is still not well understood., Objective: We investigated the association between hyperfibrinogenemia upon hospital admission and the short-term prognosis of AIS patients., Methods: A total of 3,212 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included in the present study. Hyperfibrinogenemia was defined as having a serum fibrinogen＞4.0g/L. Cox proportional hazard and logistic regression models were used to estimate the effect of hyperfibrinogenemia on all-cause in-hospital mortality and poor discharge outcome (modified Rankin Scale score≥3) in AIS patients., Results: During hospitalization, 106 patients (3.3%) died from all-cause and 1226 (38.2%) patients experienced poor functional outcome at discharge. Multivariable model adjusted for age, sex, baseline National Institutes of Health Stroke Scale score, white blood cell count and other covariates, showed that hyperfibrinogenemia was associated with a 1.76-fold increase in the risk of in-hospital mortality (hazard ratio [HR] 1.76; 95% confidence interval [CI], 1.10-2.81; P-value=0.019). However, there was no significant association between hyperfibrinogenemia and poor outcome at discharge (adjusted odds ratios[OR]1.15; 95% CI 0.86-1.53; P-value=0.338). Sensitivity and subgroup analyses also confirmed a significant association between hyperfibrinogenemia and in-hospital mortality., Conclusion: In patients with AIS, hyperfibrinogenemia at the time of admission was independently associated with increased in-hospital mortality., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Low magnesium levels are associated with an elevated risk of stroke. In this study, we investigated the association between magnesium levels on hospital admission and in-hospital mortality in acute ischemic stroke (AIS) patients., Methods: A total of 2,485 AIS patients, enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city, were included in this study. The patients were divided into 4 groups according to their level of admission magnesium: Q1 (<0.82 mmol/L), Q2 (0.82-0.89 mmol/L), Q3 (0.89-0.98 mmol/L), and Q4 (≥0.98 mmol/L). Cox proportional hazard model was used to estimate the effect of magnesium on all-cause in-hospital mortality in AIS patients., Results: During hospitalization, 92 patients (3.7%) died from all causes. The lowest serum magnesium level (Q1) was associated with a 2.66-fold increase in the risk of in-hospital mortality in comparison to Q4 (hazard ratio [HR] 2.66; 95% CI 1.55-4.56; p-trend < 0.001). After adjusting for age, sex, time from onset to hospital admission, baseline National Institutes of Health Stroke Scale score, and other potential covariates, HR for Q1 was 2.03 (95% CI 1.11-3.70; p-trend = 0.014). Sensitivity and subgroup analyses further confirmed a significant association between lower magnesium levels and a high risk of in-hospital mortality., Conclusions: Decreased serum magnesium levels at admission were independently associated with in-hospital mortality in AIS patients., (© 2017 S. Karger AG, Basel.)

Objective: To evaluate the relation of serum uric acid levels on admission with short-term clinical outcome and hemorrhagic transformation (HT) in patients with acute ischemic stroke treated with thrombolysis., Methods: A total of 230 acute ischemic stroke patients treated with thrombolysis in our stroke unit from 2010 to 2013 were included. Demographics, disease severity, the uric acid levels on admission and hemorrhagic transformation were prospectively collected. At 90 days, the scores of the modified Rankin Scale>2 (mRS>2) was defined as poor prognosis and the scores of mRS≤2 was defined as excellent outcome. Stepwise Logistic regression models were used to analyze potential factors affecting the prognosis., Results: The levels of serum uric acid in the patients with excellent outcome were significantly higher than in patients with poor outcome [(375±42) µmol/L vs (250±36) µmol/L, P=0.0026]. Logistic regression analysis revealed that high level of serum uric acid was related to excellent outcome (OR=1.25, 95% CI, 1.04-1.47, P=0.013). The serum uric acid level of non HT patients was significantly higher than the HT patients [(350±51) µmol/L vs (282±38) µmol/L, P=0.015]. After adjustment for the influence factors including age and hypertension, the level of uric acid was still negatively correlated with HT., Conclusion: Increased serum uric acid levels are associated with low incidence of HT and better prognosis in patients with stroke treated with reperfusion therapy.

Objective: Thyroid dysfunction is associated with an elevated risk of cognitive decline, but the mechanism underlying this relationship is elusive. In this study, we investigate the relationships between free thyroxine (FT4), brain frailty and clock drawing test (CDT) performance in patients with acute minor stroke or transient ischaemic attack (TIA). Design, Patients and Measurements: A total of 204 consecutive patients admitted to our hospital within 72 h after the onset of acute minor stroke or TIA were prospectively enroled and categorized in terms of quartiles of FT4 between March 2018 and August 2019. Brain frailty on magnetic resonance imaging was rated according to previously published criteria. Cognitive performance was assessed with the CDT. Results: Generalized linear analysis revealed that FT4 was independently associated with higher brain frailty score after adjusting potential confounders (β, 0.03; 95% confidence interval [CI], 0.00–0.06; p = 0.0205), which is consistent with the result of FT4 (quartile) as a categorical variable (β, 0.34; 95% CI, 0.01–0.68; p = 0.0059; ptrend = 0.0807). A nonlinear relationship was detected between FT4 and brain frailty score, which had an inflection point of 1.19. FT4 was also associated with poor CDT performance (odds ratio, 1.15; 95% CI, 1.04–1.26; p = 0.0051). And mediation analysis found that brain frailty partially mediated the positive relationship between FT4 and poor CDT performance (indirect effect = 0.0024; 95% CI, 0.0003–0.01, p = 0.04). Conclusions: Our findings suggested that a higher FT4 level was associated with a higher brain frailty score and poorer CDT performance, and brain frailty might play an important effect on the association between FT4 and cognitive decline. [ABSTRACT FROM AUTHOR]