Association of Early Longitudinal Changes in the Neutrophil-to-Lymphocyte Ratio With Adverse Clinical Outcomes in Acute Ischemic Stroke Patients After Endovascular Treatment.

BACKGROUND: We aim to elucidate the contribution of early dynamic changes in the neutrophil-to-lymphocyte ratio (NLR) to poor clinical outcomes in acute ischemic stroke patients after endovascular treatment (EVT). METHODS: Acute ischemic stroke patients who underwent EVT were consecutively recruited from January 2019 to July 2022. Blood cell counts were sampled at admission and at following 24 hours after EVT. Clinical outcome measures included 3-month functional dependence (modified Rankin scale of 3-6), symptomatic intracranial hemorrhage, and mortality at 7 days and 30 days. Multinomial logistic regressions were used to evaluate the association of changes in the NLR with unfavorable outcomes. RESULTS: A total of 590 patients were included in the final analysis. The multinomial logistic model indicated that the increasing changes in the NLR after EVT was an independent factor for poor outcomes; the adjusted odds ratio was 1.06 (95% confidence interval [CI] 1.03-1.10; P < 0.001) at poor 3-month functional outcomes, 1.07 (95% CI 1.04-1.10; P < 0.001) at symptomatic intracranial hemorrhage, 1.08 (95% CI 1.05-1.12; P < 0.001) at mortality at 7 days, and 1.04 (95% CI 1.02-1.07; P = 0.001) at mortality at 30 days. Areas under the curve of changes in NLR to discriminate adverse outcomes were 0.725, 0.687, 0.664, and 0.659, respectively. The optimal cutoff values were 5.77 (56.6% sensitivity, 81.0% specificity), 6.92 (60.0% sensitivity, 77.0% specificity), 8.64 (51.0% sensitivity, 82.0% specificity), and 8.64 (48.7% sensitivity, 83.0% specificity), respectively. CONCLUSIONS: The NLR in acute ischemic stroke patients increased remarkably independent of successful reperfusion. Elevated changes in the NLR might predict malignant hemorrhagic transformation, adverse functional outcomes, and short-term mortality.

Prevalence and Impact of Medical Complications on Clinical Outcomes in Acute Ischemic Stroke Patients After Endovascular Therapy - Data From a Comprehensive Stroke Unit in China.

OBJECTIVE: We aim to assess the incidence and impact of in-hospital medical complications (MCs) on clinical outcomes in acute ischemic stroke (AIS) patients after endovascular therapy (EVT). METHODS: AIS patients who underwent EVT were consecutively recruited from January 2019 to July 2022. The primary outcome was a poor 3-month functional outcome, defined as a modified Rankin Scale score (mRS) of 3-6. The safety variables were symptomatic intracerebral hemorrhage and mortality at 7 and 30 days. RESULTS: A total of 306 (50.1%) patients experienced at least one of the MCs. The most common MC was pneumonia (42.6%). Multivariate analysis revealed that the setting of MCs was an independent predictor of a poor 3-month functional outcome (adjusted odds ratio [aOR] 4.40, 95% confidence interval [CI] 3.01-6.42; P < 0.001). In the subgroup analysis, this trend was significant, especially in the patients aged 60-75 years (aOR 5.87, 95% CI 3.45-9.97; P < 0.001) or with baseline NIHSS (≤16) (aOR 5.05, 95% CI 2.84-9.01; P < 0.001). For individuals, cardiac events (aOR 8.56, 95% CI 4.05-18.09; P < 0.001), pneumonia (aOR 5.08, 95% CI 3.42-7.55; P < 0.001), and gastrointestinal bleeding (GIB) (aOR 6.12, 95% CI 3.40-11.01; P < 0.001) were independently associated with the poor 3-month outcome. The setting of MCs was independently associated with symptomatic intracerebral hemorrhage (aOR 2.11, 95% CI 1.22-3.64; P = 0.007) and mortality at 30 days (aOR 2.11, 95% CI 1.22-3.64; P = 0.007) after adjustment, but not with mortality at 7 days. CONCLUSIONS: MCs in AIS patients after EVT have a high incidence, despite successful reperfusion, adversely affecting clinical outcomes and increasing short-term mortality.

Large vessel occlusion stroke outcomes in diabetic vs. non-diabetic patients with acute stress hyperglycemia.

Objective: This study assesses whether stress-induced hyperglycemia is a predictor of poor outcome at 3 months for patients with acute ischemic stroke (AIS) treated by endovascular treatment (EVT) and impacted by their previous blood glucose status. Methods: This retrospective study collected data from 576 patients with AIS due to large vessel occlusion (LVO) treated by EVT from March 2019 to June 2022. The sample was composed of 230 and 346 patients with and without diabetes mellitus (DM), respectively, based on their premorbid diabetic status. Prognosis was assessed with modified Rankin Scale (mRS) at 3-month after AIS. Poor prognosis was defined as mRS>2. Stress-induced hyperglycemia was assessed by fasting glucose-to-glycated hemoglobin ratio (GAR). Each group was stratified into four groups by quartiles of GAR (Q1-Q4). Binary logistic regression analysis was used to identify relationship between different GAR quartiles and clinical outcome after EVT. Results: In DM group, a poor prognosis was seen in 122 (53%) patients and GAR level was 1.27 ± 0.44. These variables were higher than non-DM group and the differences were statistically significant (p < 0.05, respectively). Patients with severe stress-induced hyperglycemia demonstrated greater incidence of 3-month poor prognosis (DM: Q1, 39.7%; Q2, 45.6%; Q3, 58.6%; Q4, 68.4%; p = 0.009. Non-DM: Q1, 31%; Q2, 32.6%; Q3, 42.5%; Q4, 64%; p < 0.001). However, the highest quartile of GAR was independently associated with poor prognosis at 3 months (OR 3.39, 95% CI 1.66-6.96, p = 0.001), compared to the lowest quartile in non-DM patients after logistic regression. This association was not observed from DM patients. Conclusion: The outcome of patients with acute LVO stroke treated with EVT appears to be influenced by premorbid diabetes status. However, the poor prognosis at 3-month in patients with DM is not independently correlated with stress-induced hyperglycemia. This could be due to the long-term damage of persistent hyperglycemia and diabetic patients' adaptive response to stress following acute ischemic damage to the brain.

Early neurological deterioration in acute ischemic stroke patients after intravenous thrombolysis with alteplase predicts poor 3-month functional prognosis - data from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS-China).

BACKGROUND: We aimed to investigate the risk factors of early neurological deterioration (END) after intravenous thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) and the relationship between END and poor 3-month functional outcomes. METHODS: Patients who accepted intravenous recombinant rt-PA were enrolled continuously. END was defined as an increase in National Institute of Health Stroke (NIHSS) score ≥ 4 points or death within 24 hours after intravenous thrombolysis. The modified Rankin Scale (mRS) score was recorded to evaluate the functional outcome of stroke, and the poor 3-month prognosis was defined as an mRS score ≥ of 3. Univariate and multivariate analyses were used to analyze the risk factors of END. The relation between END and 3-month functional outcome was analyzed by multivariate logistic regression analysis. RESULTS: A total of 1107 patients (mean age, 63.42 ± 11.33 years; 673 males) were included in the final analysis, and 81(7.32%) patients had END. In multivariate analysis, the serum glucose level was significantly associated with END; the odds ratio was 1.10 (95% CI 1.03 to 1.18, p = 0.004). The multivariate logistic analysis showed END has a notable association with the poor 3-month functional recovery even after adjusting for confounding factors; the adjusted OR was 8.25 (95% CI 3.77 to 18.03, p < 0.0001). CONCLUSIONS: The initial serum glucose level might be an independent risk factor of END, and END might predict a poor 3-month prognosis.

Extracranial carotid plaque hemorrhage predicts ipsilateral stroke recurrence in patients with carotid atherosclerosis - a study based on high-resolution vessel wall imaging MRI.

BACKGROUND: Intraplaque hemorrhage (IPH) is a hallmark of carotid plaque vulnerability. We aim to investigate the association between IPH and recurrent ipsilateral ischemic stroke. METHODS: Patients with a recent stroke or transient ischemic attack (TIA) were prospectively recruited and underwent an ultrasonographic examination and carotid HR VWMRI on the side consistent with symptoms. Carotid plaque was defined as carotid intima-media-thickness (IMT) by ultrasound≥1.5 mm. IPH was determined that the ratio of the plaque signal intensity relative to that of adjacent muscle was > 1.5. All enrolled patients were clinically followed until an ipsilateral ischemic stroke, TIA, carotid endarterectomy (CEA)/carotid artery stenting (CAS), or death within 12 months. Univariate analysis was used to analyze the correlation between clinical characteristics and IPH. Kaplan-Meier survival analysis and a log-rank test were used to compare recurrence-free survival time between the IPH and non-IPH groups. Cox regression models evaluated IPH as the predictor of ipsilateral stroke recurrence. RESULTS: A total of 171 patients (mean age, 60.13 ± 10.04 years; 118 males) were included in the final analysis. Thirty-two patients (18.7%) showed carotid IPH. During the follow-up, patients with carotid IPH suffered 60.9% (14 of 23) of recurrent ipsilateral strokes and 60.0% (3 of 5) TIA. Multivariate Cox regression analysis proved IPH as a strong predictor of ipsilateral stroke; the adjusted hazard ratio (HR) was 6.64 (95% confidence interval [CI], 2.84-15.54, P < 0.001). Meanwhile, Cox regression analysis also proved that IPH could predict recurrent ischemic events; the adjusted HR was 8.08 (95% CI, 3.65-17.91, P < 0.001). CONCLUSIONS: Carotid intraplaque hemorrhage is strongly associated with recurrent ischemic events and could predict recurrent ipsilateral stroke.

Extracranial Carotid Plaque Hemorrhage Is Independently Associated With Poor 3-month Functional Outcome After Acute Ischemic Stroke-A Prospective Cohort Study.

Background and Purpose: Carotid plaque hemorrhage (IPH) is a critical plaque vulnerable feature. We aim to elucidate the association between symptomatic extracranial carotid atherosclerotic IPH and poor 3-month functional outcome after acute ischemic stroke by high-resolution vessel wall MRI (HRVMRI). Methods: We prospectively studied consecutive patients with a recent stroke or transient ischemic attack (TIA) of carotid atherosclerotic origin. All patients underwent a High-Resolution (HR) VWMRI scan of ipsilateral extracranial carotid within 1 week after admission. The patients recruited were interviewed by telephone after 3 months after stroke onset. The primary outcome was a 3-month functional prognosis of stroke, expressed as a modified Rankin Scale (mRS) score. A poor prognosis was defined as a 3-month modified Rankin Scale (mRS) score ≥ of 3. Univariate analysis was used to analyze the correlation between risk factors and IPH. The relation between IPH and 3-month functional outcome was analyzed by Logistic regression analysis. Results: A total of 156 patients (mean age, 61.18 ± 10.12 years; 108 males) were included in the final analysis. There were significant differences in the age, gender, smoking history, national institutes of health stroke scale (NIHSS) on admission, and diastolic blood pressure (DBP) on admission between the IPH group and the non-IPH group (all p < 0.05). During the follow-up, 32 patients (20.5%) had a poor functional outcome. According to the prognosis analysis of poor functional recovery, there was a significant difference between the two groups [36.7 vs. 16.7%; unadjusted odds ratio (OR), 2.32, 95% confidence interval (CI), 1.12-4.81, p = 0.024). Even after adjusting for confounding factors [such as age, gender, smoking history, National Institutes of Health Stroke Scale (NIHSS) on admission, DBP on admission, stenosis rate of carotid artery (CA), calcification, loose matrix, lipo-rich necrotic core (LRNC), and statins accepted at 3 months], IPH was still a strong predictor of poor 3-month outcome, and the adjusted OR was 3.66 (95% CI 1.68-7.94, p = 0.001). Conclusions: Extracranial carotid IPH is significantly associated with poor 3-month outcome after acute ischemic stroke and can predict the poor 3-month functional prognosis.

MicroRNA-323 suppresses nerve cell toxicity in cerebral infarction via the transforming growth factor-ß1/SMAD3 signaling pathway.

In the present study, the aim was to investigate the function of microRNA­323 (miR­323) in cerebral infarction and its underlying mechanism. A rat model of cerebral infarction was established and hippocampal tissues were analyzed. In addition, to further understand the role of miR­323, PC12 cells were transfected with miR­323 mimics or inhibitors and subjected to hypoxia to model cerebral infarction. Reverse transcription­quantitative polymerase chain reaction was used to measure the expression of miR­323. A luciferase reporter assay was conducted to analyze miR­323 target sites the partial sequence of the 3'­untranslated region of SMAD3 mRNA in vitro. Western blot analysis was also used to analyze transforming growth factor­ß1 (TGF­ß1) and SMAD3 protein expression levels. It was observed that miR­323 expression was significantly upregulated in rats with cerebral infarction compared with rats in the sham­control group. In addition, overexpression of miR­323 induced nerve cell toxicity and reduced nerve cell growth in an in vitro model of cerebral infarction, whereas downregulation of miR­323 caused the opposite effects on nerve cell toxicity and growth in this model. In addition, overexpression of miR­323 directly targeted and suppressed SMAD3 expression in the in vitro model of cerebral infarction, while inhibition of miR­323 induced SMAD3 expression. The use of a SMAD3 inhibitor suppressed the effect of anti­miR­323 on nerve cell toxicity in the in vitro model of cerebral infarction. Collectively, these findings suggested that miR­323 suppresses nerve cell apoptosis in cerebral infarction via the TGF­ß1/SMAD3 signaling pathway.

MicroRNA-132 modifies angiogenesis in patients with ischemic cerebrovascular disease by suppressing the NF­κB and VEGF pathway.

In the present study, the expression of microRNA (miR)­132 and the mechanism by which it modifies angiogenesis in patients with ischemic cerebrovascular disease (ICD) was investigated. RNA isolation and reverse transcription­quantitative polymerase chain reaction were used to measure miR­132 expression in patients with ICD. Inflammatory factors were measured using ELISA kits and western blotting measured B­cell lymphoma­2 (Bcl­2)­associated X/Bcl­2 ratio (Bax/Bcl­2 ratio), nuclear factor (NF)­κB p65, matrix metalloproteinase­9 (MMP­9), vascular cell adhesion molecule­1 (VCAM­1) and protein expression of inducible nitric oxide synthase (iNOS), and vascular endothelial growth factor (VEGF) protein expression. miR­132 expression in patients with ICD was lower compared with healthy volunteers. PC12 cells were used to create an oxygen glucose deprivation (OGD) model. miR­132 overexpression in an in vitro model was able to reduce tumor necrosis factor­a, interleukin (IL)­1ß, IL­6, IL­8, cyclooxygenase­2, caspase­3 and caspase­9 levels, suppress Bax/Bcl­2 ratio, NF­κB p65, MMP­9, VCAM­1, iNOS, VEGF protein expression. The results suggested that miR­132 may modify angiogenesis in patients with ICD by suppressing the NF­κB pathway and promoting the VEGF pathway, and may develop into a therapy for ICD in future research.