Impact of human serum albumin level on symptomatic cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVE: To investigate the impact of human serum albumin (HSA) levels on symptomatic cerebral vasospasm (SCVS) in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: We retrospectively reviewed the medical records. SCVS was defined as the development of a new neurological deterioration when the cause was considered to be ischemia attributable to vasospasm after other possible causes of worsening had been excluded. The aSAH patients were divided into two groups: those with SCVS (group 1) and those without SCVS (group 2). The HSA level data on the 1st, 2nd, and 3rd day after admission was collected. Multivariate logistical regression and receiver operating characteristic (ROC) analysis were performed to evaluate the ability of HSA level to predict the development of SCVS. RESULTS: A total of 270 patients were included in our study, of which 74 (27.4%) developed SCVS. The average and lowest HSA levels were lower in group 1 (P < 0.001). In univariate logistic regression, white blood cell count, neutrophil count, and average and lowest HSA levels were associated with SCVS. After adjustment for age, CT Fisher grade, Hunt-Hess grade, and WFNS grade, both the average and lowest HSA levels remained independent predictors of SCVS (P < 0.001). The CT Fisher grade was confirmed to be an independent predictor of SCVS across each model. ROC analysis revealed that the lowest HSA level was a better predictor for SCVS than average HSA level and CT Fisher grade. CONCLUSION: Clinicians are encouraged to measure HSA levels for the first 3 days after admission to predict the occurrence of SCVS after aSAH.

Clinical value of the low-grade inflammation score in aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Multiple inflammatory biomarkers have been shown to predict symptomatic cerebral vasospasm (SCVS) and poor functional outcome in patients with aneurysmal subarachnoid hemorrhage. However, the impact of the low-grade inflammation (LGI) score, which can reflect the synergistic effects of five individual inflammatory biomarkers on SCVS and poor functional outcome on aneurysmal subarachnoid hemorrhage (aSAH), has not yet been well established. The aim of this study was to evaluate the impact of the LGI score on SCVS and poor functional outcome in aSAH patients. METHODS: The LGI score was calculated as the sum of 10 quantiles of each individual inflammatory biomarker. The association of the LGI score with the risk of SCVS and poor functional outcome was analyzed with multivariate logistical regression. RESULTS: A total of 270 eligible aSAH patients were included in this study: 74 (27.4%) had SCVS, and 79 (29.3%) had poor functional outcomes. After adjusting for confounders, a higher LGI score was revealed to independently predict SCVS (OR, 1.083; 95% CI, 1.011-1.161; P = 0.024) and poor functional outcome (OR, 1.132; 95% CI, 1.023-1.252; P = 0.016), and the second and third tertile group had higher risk of SCVS than lowest tertile group (OR, 2.826; 95% CI, 1.090-7.327; P = 0.033) (OR, 3.243; 95% CI, 1.258-8.358; P = 0.015). The receiver operating characteristic (ROC) curve uncovered the ability of the LGI score to distinguish patients with and without SCVS (area under the curve [AUC] = 0.746; 95% CI, 0.690-0.797; P < 0.001) and poor functional outcomes (area under the curve [AUC] = 0.799; 95% CI, 0.746-0.845; P < 0.001), the predictive value of LGI on SCVS and poor functional outcome is superior than PLT, NLR and WBC, but there was no statistical difference between LGI and CRP for predicting SCVS (P = 0.567) and poor functional outcome (P = 0.171). CONCLUSIONS: A higher LGI which represents severe low grade inflammation status is associated with SCVS and poor functional outcome at 3 months after aSAH.

Impact of Stress Hyperglycemia on Early Neurological Deterioration in Acute Ischemic Stroke Patients Treated With Intravenous Thrombolysis.

Background and Purpose: It has been widely reported that stress hyperglycemia contributes to poor prognosis in patients experiencing acute ischemic stroke (AIS). However, its predictive value for early neurological deterioration (END) after intravenous administration of recombinant tissue-type plasminogen activator (IV-rtPA) in AIS patients is still unclear. The aim of this study was to evaluate the impact of stress hyperglycemia on the risk of END after IV-rtPA. Methods: A total of 798 consecutive patients treated with IV-rtPA were included in this study. The stress hyperglycemia ratio (SHR) was calculated as fasting plasma glucose level at admission (mg/dl)/glycosylated hemoglobin (HbAlc) (%). END was defined as a National Institutes of Health Stroke Scale Score (NIHSS) ≥ 4 points 24 h after IV-rtPA, and poor functional outcome at discharge was defined as a modified Rankin Scale (mRS) score of 3-6 at discharge. Patients with a prior history of diabetes or HbAlc ≥ 6.5% were considered to have diabetes mellitus. Patients were grouped according to SHR values. Multivariate logistical regression was used to evaluate the risk of END for patients within specific SHR categories. Results: In total, 139 (17.4%) patients had END. After adjusting for confounders, the highest tertile group had higher risks of END and poor functional outcome at discharge than those of patients in the lowest tertile group (OR, 1.95; 95% CI, 1.21-3.15; p = 0.006) (OR, 1.85; 95% CI, 1.163-2.941; p = 0.009), and the predictive value of high SHR for END was also significant in patients with diabetes mellitus (OR, 3.05; 95% CI, 1.29-7.21; p = 0.011). However, a significant association of high SHR and poor functional outcome was only found in patients without diabetes (OR, 1.85; 95% CI, 1.002-3.399; p = 0.045). Conclusion: A higher SHR predicted that patients with severe stress hyperglycemia had higher risks of END and poor functional outcome at discharge after IV-rtPA.

The relationship between the platelet to leukocyte ratio and mechanical thrombectomy outcomes in acute ischemic stroke patients.

BACKGROUND AND PURPOSE: The predictive effect of blood cell ratio on ischemic event has been widely confirmed. Whether PWR and PNR can assess the risk of endovascular treatment (EVT) is largely unclear. This study aimed to investigate the prognostic value of PNR and PWR in acute ischemic stroke patients treated with EVT. METHODS: Poor functional outcome was defined as Modified Rankin Scale (mRS) of 3-6 at 3 months, Symptomatic intracranial hemorrhage (sICH) was diagnosed based on CT scan and classified according to the criterial of Heidelberg Bleeding Classification. Binary logistical regression was used to analyze the relationship of PWR, PNR with functional outcome and symptomatic intracranial hemorrhage (sICH). RESULTS: Patients with good prognosis had higher PNR and PWR value (29 vs. 24, P=0.002) (22 vs. 19, P=0.009), a lower rate of sICH (2.9% vs. 24.9%, P<0.001). In model 1, the lower PNR significantly associated with poor functional outcome (OR, 0.48; 95% CI 0.26-0.88; P=0.018), and sICH (OR, 0.42; 95% CI 0.19-0.91; P=0.028). The lower PWR only significantly associated with poor prognosis (OR, 0.97; 95% CI 0.94-1.00; P=0.038), and had a trend relation with sICH (OR, 0.98; 95% CI 0.94-1.02; P=0.328). In model 2 lower PNR still significantly associated with poor functional outcome (OR, 0.53; 95% CI 0.29-0.99; P=0.047), but showed a trend for predicting sICH (OR, 0.56; 95% CI 0.25-1.25; P=0.158). CONCLUSION: Platelet to leukocyte ratio may be use to assess the risk of functional outcome and sICH in patients with acute anterior circulation occlusion stroke undergoing endovascular treatment in real world China.

CircPRKCI-miR-545/589-E2F7 axis dysregulation mediates hydrogen peroxide-induced neuronal cell injury.

Excessive oxidative stress induces significant injury and cytotoxicity to neuronal cells. The current study tested expression and the potential function of the circular RNA PRKCI (circPRKCI) in oxidative stress-injured neuronal cells. In cultured SH-SY5Y neuronal cells, hydrogen peroxide (H2O2) downregulated circPRKCI expression, causing accumulation of miR-545 and miR-589, but reduction of their target, the transcription factor E2F7. Importantly, ectopic overexpression of circPRKCI in SH-SY5Y cells significantly attenuated H2O2-induced cytotoxicity. Conversely, siRNA-mediated knockdown of circPRKCI induced SH-SY5Y cell death and apoptosis. Further studies demonstrated that H2O2-induced cytotoxicity in SH-SY5Y cells was inhibited by miR-545/589 inhibitors, but mimicked by miR-545/589 mimics. Importantly, CRISPR/Cas9-mediated knockout (KO) of E2F7 induced potent SH-SY5Y cell death and apoptosis. Furthermore, transfection of circPRKCI siRNA or miR-545/589 mimics were ineffective in E2F7 KO cells. In the primary human neurons, H2O2 stimulation similarly induced circPRKCI downregulation, miR-545/589 accumulation and E2F7 reduction. Moreover, H2O2-induced death and apoptosis in the primary neurons were significantly inhibited by circPRKCI overexpression or miR-545/589 inhibitors. Taken together, our results show that dysregulation of circPRKCI-miR-545/589-E2F7 axis mediated H2O2-induced neuronal cell injury. Targeting this novel cascade could be a fine strategy to protect neurons from oxidative stress.

Factors Associated with Thrombolysis Outcome in Ischemic Stroke Patients with Atrial Fibrillation.

The outcome of early intravenous thrombolysis for ischemic stroke in patients with atrial fibrillation (AF) is worse than that without thrombosis. How to increase the efficacy of intravenous thrombolysis for AF-related ischemic stroke remains largely unknown. In this study, we investigated factors that influence the effect of intravenous thrombolysis in these patients. Our results showed that thrombolysis was independently associated with a favorable outcome (P < 0.001) and did not influence the mortality of AF-related ischemic stroke, although it increased the risk of hemorrhage within 24 h after treatment. Risk factors for a poor outcome at admission were: heart failure (P = 0.045); high systolic pressure (P = 0.039); high blood glucose (P = 0.030); and a high National Institutes of Health Stroke Scale (NIHSS) score (P < 0.001). Moreover, high systolic pressure at admission (P = 0.007), high blood glucose (P = 0.027), and a high NIHSS score (P < 0.001) were independent risk factors for mortality at 3 months. Besides thrombolysis, a high NIHSS score (P = 0.006) and warfarin taken within 48 h before stroke onset (P = 0.032) were also independent risk factors for symptomatic hemorrhage within 24 h after treatment. Ischemic stroke patients with AF benefited from intravenous thrombolysis with recombinant tissue plasminogen activator within 4.5 h after stroke.

Human umbilical cord mesenchymal stem cells protect against ischemic brain injury in mouse by regulating peripheral immunoinflammation.

Current treatments for ischemic stroke are limited, stem cell transplantation offers great potential as a therapeutic strategy. The present study was undertaken to determine whether human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) could improve brain injury after middle cerebral artery occlusion (MCAO) through modulating peripheral immunoinflammation. The study showed that neurological deficit was ameliorated and brain edema, infarct volume was significantly decreased from 72 h to 1 week post-MCAO with hUC-MSCs treatment via tail vein injection within 30 mins after stroke; hUC-MSCs attenuated the levels of inflammatory factors including IL-1, TNF-α, IL-23, IL-17 and IL-10 in peripheral blood serum and ischemia hemisphere after stroke; hUC-MSCs significantly decreased the level of Th17 cells at 24h and increased the level of Tregs at 72 h post-MCAO in peripheral immune system; the level of TGF-ß in blood serum was enhanced by hUC-MSCs. In conclusion, our findings suggested that hUC-MSCs had neuroprotection in MCAO mice by TGF-ß modulating peripheral immune and hUC-MSCs may be as a potential therapy for ischemic stroke.

Thrombolysis on ischemic stroke patients with decreased level of consciousness within 4.5 h.

BACKGROUND AND PURPOSE: Few reports concerned on recombinant tissue plasminogen activator (rt-PA) treatment in stroke patients with decreased consciousness. This study assesses the efficacy and safety of intravenous rt-PA administration within 4.5 h in stroke patients with decreased consciousness. METHODS: A total of 136 stroke patients with decreased consciousness, who received or not rt-PA intravenously within 4.5 h after stroke onset from Jiangsu province of China from 2009 to 2012, were reviewed retrospectively. Glasgow Coma Scale (GCS), National Institute of Health Stroke Scale (NIHSS), intracranial hemorrhage rate, and mortality were used to determine patient outcome when discharged. A 3-month outcome was calculated by modified Rankin Scale (mRS) with score 0 to 1 considered favorable outcome. RESULTS: Baseline characteristics of two groups were similar. When discharged, no significant differences were observed regarding NIHSS score (P = 0.994) or GCS score (P = 0.591) between groups. After 3 months, 22.8% patients in rt-PA group had favorable outcome as compared with 7.5% patients in control group (P = 0.014). Treatment with rt-PA did not significantly increase incidence of hemorrhage (P = 0.494) or mortality (P = 0.169). CONCLUSIONS: Intravenous rt-PA administration within 4.5 h after onset of symptoms benefited stroke patients with abnormal consciousness.