Non-coding RNAs in acute ischemic stroke: from brain to periphery.

Acute ischemic stroke is a clinical emergency and a condition with high morbidity, mortality, and disability. Accurate predictive, diagnostic, and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain undetermined. With innovations in high-throughput gene sequencing analysis, many aberrantly expressed non-coding RNAs (ncRNAs) in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental models. Differentially expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes, leading to neuroprotection or deterioration, thus ncRNAs can serve as therapeutic targets in acute ischemic stroke. Moreover, distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction, diagnosis, and prognosis. In particular, ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic stroke. In this review, we consolidate the latest progress of research into the roles of ncRNAs (microRNAs, long ncRNAs, and circular RNAs) in the pathological processes of acute ischemic stroke-induced brain damage, as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction, diagnosis, and prognosis. Findings from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.

Overexpression of low-density lipoprotein receptor prevents neurotoxic polarization of astrocytes via inhibiting NLRP3 inflammasome activation in experimental ischemic stroke.

JOURNAL/nrgr/04.03/01300535-202502000-00027/figure1/v/2024-05-28T214302Z/r/image-tiff Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury. Low-density lipoprotein receptor, a classic cholesterol regulatory receptor, has been found to inhibit NLR family pyrin domain containing protein 3 (NLRP3) inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer's disease. However, little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic stroke. To address this issue in the present study, we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke models. First, we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting analysis. We observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/reoxygenation. Second, we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated virus. Low-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective phenotype. Finally, we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin, an NLRP3 agonist, restored the neurotoxic astrocyte phenotype. These findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.

Relationship Between Liver Fibrosis and Increased Risk of Symptomatic Intracranial Hemorrhage in Ischemic Stroke Patients Undergoing Mechanical Thrombectomy.

Background: Liver fibrosis has been reported to be associated with hematoma expansion and mortality in patients with intracerebral hemorrhage. This study aimed to detect the association between liver fibrosis and symptomatic intracranial hemorrhage (sICH) in ischemic stroke after mechanical thrombectomy (MT). Methods: We retrospectively included patients with large artery occlusion in the anterior circulation and treated with MT at a single stroke center. The fibrosis-4 index (FIB-4) was used to assess the severity of liver fibrosis. sICH was diagnosed according to the Heidelberg Bleeding Classification criteria. Multivariate logistic regression and restricted cubic spline analysis were conducted to examine the relationship between liver fibrosis and sICH. Results: Among the 578 patients (mean age, 70.1 years; 58.5% male) included in the study, 65 (11.2%) individuals were diagnosed with sICH. After adjusting for demographic characteristics and other potential confounders, a higher FIB-4 index was found to be independently associated with an increased risk of sICH (odds ratio: 1.306, 95% confidence interval: 1.127-1.512, P=0.001). Similar results were obtained when analyzing FIB-4 as a categorical variable. Conclusion: This study demonstrated that there is a significant association between FIB-4 and the risk of sICH in patients with acute ischemic stroke who underwent MT. Therefore, liver fibrosis could serve as a valuable parameter in monitoring the risk of sICH following MT.

Association of Chinese visceral adiposity index with clinical outcome in patients after endovascular thrombectomy.

BACKGROUND AND PURPOSE: The Chinese Visceral Adiposity Index (CVAI) is a reliable indicator of visceral adiposity dysfunction in the Chinese population. We aimed to evaluate the association between CVAI and clinical outcome in Chinese ischemic stroke patients who received endovascular thrombectomy (EVT). METHODS: This study retrospectively included patients with large vessel occlusive stroke receiving EVT treatment in 2 China stroke centers. Baseline CVAI was calculated after admission. Patients with a modified Rankin scale score ≥ 3 at 3 months after ischemic stroke were defined as poor outcome. Binary multivariate logistic regression models were utilized to explore the association between CVAI and the risk of 90-day unfavorable outcome. RESULTS: A total of 453 patients (mean age, 70.4  ± 12.1 years; 280 male) were included. During the 90-day follow-up, 236 (52.1 %) patients experienced poor outcome. After multivariable adjustment for potential confounders, increasing CVAI was associated with an increased risk of 90-day poor outcome (odds ratios, per-standard deviation increase: 1.521; 95 % confidence interval, 1.127-2.052; P = 0.006). Similar significant results were observed when the CVAI was analyzed as a categorical variable. Furthermore, the multiple-adjusted spline regression model showed an inverted J-shape association between CVAI and risk of unfavorable outcome (P = 0.048 for non-linearity). CONCLUSIONS: This study demonstrated that CVAI is positively correlated with 90-day poor outcome in Chinese ischemic stroke patients after EVT.

Dynamic and visual nomograms to online predict unfavorable outcome of mechanical thrombectomy for acute basilar artery occlusion.

BACKGROUND: The evidence of mechanical thrombectomy (MT) in basilar artery occlusion (BAO) was limited. This study aimed to develop dynamic and visual nomogram models to predict the unfavorable outcome of MT in BAO online. METHODS: BAO patients treated with MT were screened. Preoperative and postoperative nomogram models were developed based on clinical parameters and imaging features. An independent dataset was collected to perform external validation. Web-based calculators were constructed to provide convenient access. RESULTS: A total of 127 patients were included in the study, and 117 of them were eventually included in the analysis. The nomogram models showed robust discrimination, with an area under the receiver operating characteristic (ROC) of 0.841 (preoperative) and 0.916 (postoperative). The calibration curves showed good agreement. The preoperative predictors of an unfavorable outcome were previous stroke, the National Institutes of Health Stroke Scale (NIHSS) at admission, and the posterior circulation Alberta Stroke Program Early Computed Tomography Score (pc-ASPECTS). The postoperative predictors were previous stroke, NIHSS at 24 h, and pc-ASPECTS. CONCLUSION: Dynamic and visual nomograms were constructed and validated for the first time for BAO patients treated with MT, which provided precise predictions for the risk of an unfavorable outcome. The preoperative model may assist clinicians in selecting eligible patients, and the postoperative model may facilitate individualized poststroke management.

Adult children and older people's demand for community care services in urban China.

OBJECTIVES: This paper has two objectives. First, it assesses whether the existing informal care provided by adult children has an impact on older people's propensity to demand community care services. Second, it compares the different statuses of sons and daughters in the formal/informal support trade-off. METHODS: The paper is based on an analysis of data from the 2018 wave of the China Longitudinal Ageing Social Survey, within the framework of a revised version of Andersen's model, and applies multilevel models to analyse the effects of adult children's gender, numbers and the quality of their support, on older people's willingness to purchase community care services. RESULTS: Older people who had sons as well as daughters demanded fewer services, while the number of sons increased service demand. Regarding sons, community care services compensated for economic support, daily life care and spiritual consolation, but did so only in respect of daily life care from daughters. CONCLUSIONS: Many families have only one son or one daughter as a result of the one-child policy and therefore often require support from formal care services. Moreover, there is a distinct gender division and an influential filial culture governing the impact of services on the support provided by adult children. Because ageing in place depends on both informal family support and formal services, this key policy goal is at risk if the latter provides insufficient support to the former.

Association of tirofiban with improvement of functional outcomes of direct thrombectomy for acute anterior circulation occlusion: a retrospective, nonrandomized, multicenter, real-world study.

OBJECTIVE: Although tirofiban and endovascular thrombectomy have been widely used in the treatment of acute ischemic stroke (AIS) patients, the effectiveness of their combined application remains a subject of debate. This study aimed to assess the efficacy and safety of tirofiban in direct thrombectomy for AIS with anterior circulation vessel occlusion. METHODS: A total of 204 patients undergoing direct thrombectomy between January 2020 and December 2021 for AIS with anterior circulation vessel occlusion from four hospitals were included in this study. Patients at high risk of reocclusion with severe atherosclerosis, those who achieved successful recanalization for ≥ 3 stent retriever passes, or those who underwent emergency stenting or balloon angioplasty for severe residual stenosis were treated with tirofiban. Following a low-dose intra-arterial bolus (0.25-1 mg) immediately after endovascular treatment, tirofiban was administered continuously through intravenous infusion (0.1 µg/kg/min) for 12-24 hours. The primary efficacy outcome was evaluated using the 90-day modified Rankin Scale score. The safety outcome was assessed using symptomatic intracerebral hemorrhage (sICH) and mortality rates. RESULTS: The tirofiban group and nontirofiban group each included 102 patients. The favorable outcome rate in the tirofiban group was significantly higher than that in the nontirofiban group (53.9% vs 35.3%, p = 0.007). However, the sICH and 90-day mortality rates were lower in the tirofiban group, despite a lack of statistical significance (sICH: 15.7% vs 16.7%, p = 0.849; 90-day mortality: 16.67% vs 24.51%, p = 0.166). Finally, it was found that older patients (> 72 years), male patients, patients with admission National Institutes of Health Stroke Scale scores > 14, patients with a time from onset to reperfusion > 327 minutes, and patients with a medical history of diabetes tend to benefit from tirofiban treatment. CONCLUSIONS: This study suggests that tirofiban combined with direct thrombectomy improves functional outcomes of AIS and reduces the 90-day mortality rate. Therefore, it could be considered as a suitable treatment option for AIS patients with anterior circulation vessel occlusion.

Prior statin use in acute ischemic stroke patients with mechanical thrombectomy: A prospective cohort study in China.

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) has been proven to be effective for selected patients with acute ischemic stroke (AIS). However, conflicting findings have suggested the association between prior statin use and outcomes in AIS patients with MT, with a particular lack of information in the Chinese population. Via a prospective cohort study, we explored the safety and efficacy of prior statin use in Chinese AIS patients with MT. METHODS: We consecutively enrolled AIS patients treated with MT from the First Affiliated Hospital of Chengdu Medical College and Nanjing First Hospital between June 2015 and June 2022 who were under prior statin use or not. Safety and efficacy outcomes were prospectively followed. The primary outcomes were defined as 90-day favorable outcomes (mRS score 0-2). Secondary outcomes included successful recanalization (TICI≥2b), early neurological improvement (decrease of National Institutes of Health Stroke Scale (NIHSS) score ≥ 4 points at 24 h), symptomatic intracerebral hemorrhage (sICH), and death at 90 days. RESULTS: We enrolled 334 patients in total, 50 of whom (15.0%) undertaken statins administration before AIS. 117 (35.0%) patients had favorable outcomes at 90 days, 288 (86.2%) patients had successful recanalization, 108 (32.3%) patients achieved early neurological improvement, 41 (12.3%) patients had sICH and 73 (21.9%) patients died within 90 days. The 90-day favorable outcomes were not significantly different (adjusted OR=0.853, 95% CI 0.449-1.620, P = 0.626) between prior statins use group and no statins use group. There was no significant difference in recanalization (adjusted OR=1.466, 95% CI 0.536-4.009, P = 0.456), early neurological improvement (adjusted OR=1.568, 95% CI 0.811-3.032, P = 0.181), sICH (adjusted OR=0.850, 95% CI 0.325-2.224, P = 0.741), ICH (adjusted OR=1.029, 95% CI 0.479-2.490, P = 0.942), and 90-day mortality (adjusted OR=0.381, 95% CI 0.091-1.586, P = 0.185) between the two groups. CONCLUSIONS: Prior statin use may be safe for Chinese AIS patients with MT, but its efficacy warrants further research.

The Potential of Gut Microbiota in Prediction of Stroke-Associated Pneumonia.

BACKGROUND: Stroke-associated pneumonia (SAP) is a common stroke complication, and the changes in the gut microbiota composition may play a role. Our study aimed to evaluate the predictive ability of gut microbiota for SAP. METHODS: Acute ischemic stroke patients were prospectively enrolled and divided into two groups based on the presence or absence of SAP. The composition of gut microbiota was characterized by the 16S RNA Miseq sequencing. The gut microbiota that differed significantly between groups were incorporated into the conventional risk scores, the Acute Ischemic Stroke-Associated Pneumonia Score (AIS-APS), and the Age, Atrial fibrillation, Dysphagia, Sex, Stroke Severity Score (A2DS2). The predictive performances were assessed in terms of the area under the curve (AUC), the Net Reclassification Improvement (NRI), and the Integrated Discrimination Improvement (IDI) indices. RESULTS: A total of 135 patients were enrolled, of whom 43 had SAP (31%). The short-chain fatty acids (SCFAs)-producing bacteria, such as Bacteroides, Fusicatenibacter, and Butyricicoccus, were decreased in the SAP group. The integrated models showed better predictive ability for SAP (AUC = 0.813, NRI = 0.333, p = 0.052, IDI = 0.038, p = 0.018, for AIS-APS; AUC = 0.816, NRI = 0.575, p < 0.001, IDI = 0.043, p = 0.007, for A2DS2) in comparison to the differential genera (AUC = 0.699) and each predictive score (AUCAISAPS = 0.777; AUCA2DS2 = 0.777). CONCLUSIONS: The lower abundance of SCFAs-producing gut microbiota after acute ischemic stroke was associated with SAP and may play a role in SAP prediction.

Percutaneous angioplasty and/or stenting versus aggressive medical therapy in patients with symptomatic intracranial atherosclerotic stenosis: a 1-year follow-up study.

Background: Symptomatic intracranial atherosclerotic stenosis (sICAS) is one of the common causes of ischemic stroke. However, the treatment of sICAS remains a challenge in the past with unfavorable findings. The purpose of this study was to explore the effect of stenting versus aggressive medical management on preventing recurrent stroke in patients with sICAS. Methods: We prospectively collected the clinical information of patients with sICAS who underwent percutaneous angioplasty and/or stenting (PTAS) or aggressive medical therapy from March 2020 to February 2022. Propensity score matching (PSM) was employed to ensure well-balanced characteristics of two groups. The primary outcome endpoint was defined as recurrent stroke or transient ischemic attack (TIA) within 1 year. Results: We enrolled 207 patients (51 in the PTAS and 156 in the aggressive medical groups) with sICAS. No significant difference was found between PTAS group and aggressive medical group for the risk of stroke or TIA in the same territory beyond 30 days through 6 months (P = 0.570) and beyond 30 days through 1 year (P = 0.739) except for within 30 days (P = 0.003). Furthermore, none showed a significant difference for disabling stroke, death and intracranial hemorrhage within 1 year. These results remain stable after adjustment. After PSM, all the outcomes have no significant difference between these two groups. Conclusion: The PTAS has similar treatment outcomes compared with aggressive medical therapy in patients with sICAS across 1-year follow-up.

Higher Serum E-Selectin Levels Associated with Malignant Brain Edema after Endovascular Thrombectomy for Ischemic Stroke: A Pilot Study.

Background and Purpose: Little is known about the effect of soluble adhesion molecules on malignant brain edema (MBE) after endovascular thrombectomy (EVT). This study aimed to explore the association between serum concentrations of E-selectin and the risk of MBE in patients who received EVT. Methods: Patients with a large vessel occlusion stroke in the anterior circulation who underwent EVT were prospectively recruited. Serum soluble E-selectin concentrations were measured after admission for all patients. MBE was defined as a midline shift of ≥5 mm on follow-up imaging within 72 h after surgery. Multivariate logistic regression analyses were performed to determine the association between E-selectin levels and the risk of MBE. Results: Among the 261 included patients (mean age, 69.7 ± 12.3 years; 166 males), 59 (22.6%) developed MBE. Increasing circulating E-selectin levels were associated with an increased risk of MBE after multivariable adjustment (odds ratios [OR], highest vs. lowest quartile: 3.593; 95% confidence interval [CI], 1.178-10.956; p = 0.025). We further observed a significantly positive association between E-selectin and MBE (per 1-standard deviation increase; OR, 1.988; 95% CI, 1.379-2.866, p = 0.001) when the E-selectin levels were analyzed as a continuous variable. Furthermore, the restricted cubic spline demonstrated a linear correlation between serum E-selectin levels and the risk of MBE (p < 0.001 for linearity). Conclusions: In this prospective study, circulating levels of E-selectin were associated with an increased risk of MBE after EVT. Further mechanistic studies are warranted to elucidate the pathophysiology underlying this association.

Interpretable Machine Learning Model Predicting Early Neurological Deterioration in Ischemic Stroke Patients Treated with Mechanical Thrombectomy: A Retrospective Study.

Early neurologic deterioration (END) is a common and feared complication for acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT). This study aimed to develop an interpretable machine learning (ML) model for individualized prediction to predict END in AIS patients treated with MT. The retrospective cohort of AIS patients who underwent MT was from two hospitals. ML methods applied include logistic regression (LR), random forest (RF), support vector machine (SVM), and extreme gradient boosting (XGBoost). The area under the receiver operating characteristic curve (AUC) was the main evaluation metric used. We also used Shapley Additive Explanation (SHAP) and Local Interpretable Model-Agnostic Explanations (LIME) to interpret the result of the prediction model. A total of 985 patients were enrolled in this study, and the development of END was noted in 157 patients (15.9%). Among the used models, XGBoost had the highest prediction power (AUC = 0.826, 95% CI 0.781-0.871). The Delong test and calibration curve indicated that XGBoost significantly surpassed those of the other models in prediction. In addition, the AUC in the validating set was 0.846, which showed a good performance of the XGBoost. The SHAP method revealed that blood glucose was the most important predictor variable. The constructed interpretable ML model can be used to predict the risk probability of END after MT in AIS patients. It may help clinical decision making in the perioperative period of AIS patients treated with MT.

The Role of High-Resolution Magnetic Resonance Imaging in Cerebrovascular Disease: A Narrative Review.

High-resolution magnetic resonance imaging (HRMRI) is the most important and popular vessel wall imaging technique for the direct assessment of vessel wall and cerebral arterial disease. It can identify the cause of stroke in high-risk plaques and differentiate the diagnosis of head and carotid artery dissection, including inflammation, Moya Moya disease, cerebral aneurysm, vasospasm after subarachnoid hemorrhage, reversible cerebral vasoconstriction syndrome, blunt cerebrovascular injury, cerebral arteriovenous malformations, and other stenosis or occlusion conditions. Through noninvasive visualization of the vessel wall in vitro, quantified assessment of luminal stenosis and pathological features of the vessel wall can provide clinicians with further disease information. In this report, technical considerations of HRMRI are discussed, and current clinical applications of HRMRI are reviewed.

Blood pressure excursion on admission and intravenous thrombolysis in ischemic stroke.

BACKGROUND: Blood pressure (BP) excursion on admission was common in patients with acute ischemic stroke, but its influence on thrombolysis effect was not fully evaluated. METHODS: Patients with acute ischemic stroke who received thrombolysis without subsequent thrombectomy were included. Admission BP excursion was defined as higher than 185/110 mmHg. Multivariate logistic regression analysis was used to evaluate the relationship between admission BP excursion and poor outcome as well as hemorrhage rates and mortality. Poor outcome was defined as a 90-day modified Rankin Scale score 3-6. Subgroup analysis was performed according to stroke severity, which was assessed by the National Institutes of Health Stroke Scale (NIHSS) score, and hypertension status. RESULTS: A total of 633 patients were enrolled and 240 participants (37.9%) had admission BP excursion. Admission BP excursion was associated with poor outcome [adjusted odds ratio (OR) 0.64, 95% confidence interval 0.42-0.99, P  = 0.046]. No significant difference was found regarding hemorrhage rates or mortality between patients with and without admission BP excursion. In subgroup analysis, admission BP excursion was related to poor outcome in patients with NIHSS score at least 7 (adjusted OR 1.89, 95% confidence interval 1.03-3.45, P  = 0.038), but not in patients with NIHSS score less than 7 ( P for interaction <0.001). CONCLUSION: Admission BP excursion above the guideline thresholds did not increase postthrombolysis hemorrhage risk or mortality, but was associated with poor outcome, especially in patients with severe stroke.

Malnutrition and poststroke depression in patients with ischemic stroke.

BACKGROUND: Identifying high-risk patients based on modifiable clinical characteristics, such as malnutrition, is critical to intervening with these variables to reduce the risk of post-stroke depression (PSD). The aim of this study was to investigate the effect of nutritional status on the risk of incident PSD and the trajectory of PSD risk. METHODS: Consecutive patients with acute ischemic stroke were recruited in this observational cohort and followed up for 1 year. Multivariate logistic regressions and multilevel mixed-effects logistic regressions with random intercepts and slopes were used to investigate the effects of nutritional indexes [the Controlling Nutritional Status (CONUT) score, the Nutritional Risk Index (NRI), and the Prognostic Nutritional Index (PNI)] and body mass index (BMI) on the risk of incident PSD and the trajectory of PSD risk over the 12-month observation period. RESULTS: A total of 538 patients were included in the final analysis. Worsening CONUT [odds ratio (OR) = 1.36; confidence interval (CI): 1.15-1.61], NRI (OR = 0.91; CI: 0.87-0.96) and PNI (OR = 0.89; CI: 0.84-0.95) scores were significantly associated with an increased risk of incident PSD. Moderate and severe risk malnutrition statuses were associated with higher incidences of PSD regardless of the malnutrition index (CONUT, NRI or PNI). Additionally, PSD risk decreased over time with a significant two-way interaction between time and CONUT, NRI, and PNI, implying that patients with elevated exposure to malnutrition showed a slower decline in PSD risk. BMI had no significant effect on the occurrence and development of PSD. CONCLUSION: Malnutrition, but not BMI, was associated with a higher probability of incident PSD and was more likely to lead to a slower rate of decline in PSD risk.

Endothelial Dysfunction and Parenchymal Hematoma in Ischemic Stroke Patients after Endovascular Thrombectomy.

INTRODUCTION: Endothelial dysfunction (ED) may result in parenchymal injury and therefore worsen the outcomes of ischemic stroke. This study aimed to determine whether ED could predict parenchymal hematoma (PH) in ischemic stroke patients treated with endovascular thrombectomy (EVT). METHODS: Patients with large artery occlusion in the anterior circulation and treated with EVT were prospectively enrolled from 2 stroke centers. Serum soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, soluble E-selectin, and von Willebrand factor (vWF) were tested and summed to a standardized score to reflect the levels of ED. PH was diagnosed according to the Heidelberg Bleeding Classification. RESULTS: Of the 325 enrolled patients (mean age, 68.6 years; 207 men), 41 (12.6%) developed PH. Patients with PH had higher concentrations of soluble E-selectin, vWF, and ED sum score. After adjusting for demographic characteristics, National Institutes of Health Stroke Scale score, pretreatment Alberta stroke program early computed tomography score, and other potential confounders, the increased ED burden was associated with PH (odds ratio, 1.432; 95% confidence interval, 1.031-1.988; p = 0.032). Similar significant results were found in the sensitivity analysis. The multiple-adjusted spline regression model showed a linear association between the total ED score and PH (p = 0.001 for linearity). Adding the ED score to the conventional model significantly improved the risk prediction of PH (net reclassification improvement = 25.2%, p = 0.001; integrated discrimination index = 2.9%; p = 0.001). CONCLUSIONS: This study demonstrated that ED might be related to PH. Introducing the ED score could increase the reliability of the PH risk model for stroke patients treated with EVT.

Prognostic performance of serum YKL-40 for one-year clinical outcomes in acute ischemic stroke.

BACKGROUND: Effects of YKL-40 on one-year clinical outcomes including poor clinical outcome, all-cause mortality, and stroke recurrence among acute ischemic stroke (AIS) patients remained elusive. The purpose of this study was to explore the association between serum YKL-40 at admission and one-year clinical outcomes in AIS patients. METHODS: In this prospective cohort study, a total of 1002 participants out of 1361 AIS patients from two centers were included for current analysis. Serum YKL-40 concentrations were measured via enzyme-linked immunosorbent assay. Multivariable logistic or Cox regression were performed to explore the independent association of YKL-40 with one-year clinical outcomes, including poor outcome (modified Rankin Scale of 3-6), all-cause mortality, and recurrent stroke. C-statistic, net reclassification index (NRI) and integrated discrimination improvement (IDI) were calculated to evaluate the discriminatory and predictive power of YKL-40 when added to conventional model. RESULTS: Compared with the first quartile of YKL-40, the adjusted odds ratios or hazard ratios with 95% confidence intervals of the fourth quartile were 3.032 (1.627-5.650) for poor outcome, 2.886 (1.320-6.308) for all-cause mortality and 1.694 (0.906-3.169) for recurrent stroke. The addition of serum YKL-40 to conventional model significantly improved reclassification for poor outcome (NRI 0.053, P = 0.031; IDI 0.018, P = 0.001) and all-cause mortality (NRI 0.162, P = 0.036). CONCLUSIONS: Elevated serum YKL-40 at admission might be independently associated with one-year poor outcome and all-cause mortality but not stroke recurrence among Chinese AIS patients.

The prognostic value of caveolin-1 levels in ischemic stroke patients after mechanical thrombectomy.

BACKGROUND AND PURPOSE: The impact of serum caveolin-1 (Cav-1) on clinical outcomes in patients after mechanical thrombectomy (MT) is unclear. We aimed to investigate the association between serum cav-1 levels and the 3-month functional outcome. METHODS: We prospectively enrolled and analyzed patients with an anterior circulation large vessel occlusion who underwent MT. Serum cav-1 concentrations were tested after admission. The primary outcome was a 90-day modified Rankin Scale score of 3-6. RESULTS: Of the 237 recruited patients (mean age, 69.7 ± 12.1 years; 152 male), 131 (55.3%) experienced a 90-day poor outcome. After adjustment for demographic characteristics and other covariates, patients with higher serum Cav-1 levels had a reduced risk of poor outcome at 3 months (Per 1-standard deviation increase; odd ratios [OR], 0.59; 95% confidence interval [CI], 0.39 - 0.89, P = 0.013). Elevated Cav-1 concentrations (Per 1-standard deviation increase; OR, 0.59; 95% CI, 0.40 - 0.88, P = 0.011) were significantly associated with a favorable shift in modified Rankin Scale score distribution. Similar results were confirmed when the Cav-1 levels were analyzed as a categorical variable. Furthermore, the restricted cubic spline showed a linear association between Cav-1 levels and 90-day poor outcome (P = 0.032 for linearity). CONCLUSIONS: Increased serum Cav-1 levels were associated with improved prognosis at 3 months in ischemic stroke patients after MT, suggesting that Cav-1 may be a potential prognostic biomarker for ischemic stroke after reperfusion therapy.

Serum YKL-40 Levels and White Matter Hyperintensities in Patients with Acute Ischemic Stroke.

Background: White matter hyperintensity (WMH) is associated with risk of acute ischemic stroke (AIS) and poor outcomes after AIS. The purpose of this prospective study was to evaluate the association between serum YKL-40 levels and WMH burden in patients with AIS. Methods: From February 2020 to March 2021, a total of 672 consecutive AIS patients with magnetic resonance imaging data were prospectively recruited form two centers. Serum YKL-40 levels were quantified using enzyme-linked immunosorbent assay. The burden of WMH was semiquantitatively measured by the Fazekas visual grading scale. According to severity of overall WMH, patients were dichotomized into none-mild WMH group (Fazekas score 0-2) or moderate-severe WMH group (Fazekas score 3-6). Besides, based on severity of periventricular WMH (PV-WMH) and deep WMH (D-WMH), patients were categorized as none-mild (Fazekas score 0-1) or moderate-severe (Fazekas score 2-3). Results: Among the 672 patients, 335 (49.9%) participants were identified with moderate-severe overall WMH, 326 (48.5%) with moderate-severe PV-WMH and 262 (39.0%) with moderate-severe D-WMH. Compared with the first quartile of serum YKL-40, the adjusted odds ratio (OR) of the fourth quartile for moderate-severe PV-WMH was 2.473 (95% confidence interval [CI] 1.316-4.646; P=0.005). No significant association was observed between YKL-40 and overall WMH (OR 0.762; 95% CI 0.434-1.336; P=0.343) or D-WMH (OR 0.695; 95% CI 0.413-1.171; P=0.172). Conclusion: Our results suggested that higher YKL-40 levels appeared to be associated with PV-WMH, but not with overall WMH or D-WMH in patients with AIS.

Associations of Lipoprotein(a) Level with Cerebral Small Vessel Disease in Patients with Alzheimer's Disease.

BACKGROUND: This study aimed to examine the association of lipoprotein(a) [Lp(a)] level with the burden of cerebral small vessel disease (CSVD) in patients with Alzheimer's disease (AD). METHODS: Data from 111 consecutive patients with AD admitted to Nanjing First Hospital from 2015 to 2022 were retrospectively analyzed in this study. Serum Lp(a) concentrations were grouped into tertiles (T1-T3). Brain magnetic resonance imaging (MRI) was rated for the presence of CSVD, including enlarged perivascular spaces (EPVS), lacunes, white-matter lesions, and cerebral microbleeds (CMBs). The CSVD burden was calculated by summing the scores of each MRI marker at baseline. A binary or ordinal logistic regression model was used to estimate the relationship of serum Lp(a) levels with CSVD burden and each MRI marker. RESULTS: Patients with higher tertiles of Lp(a) levels were less likely to have any CSVD (T1, 94.6%; T2, 78.4%; T3, 66.2%; p = 0.013). Multivariable analysis found that Lp(a) levels were inversely associated with the presence of CSVD (T2 vs. T1: adjusted odds ratio [aOR] 0.132, 95% confidence interval [CI] 0.018-0.946, p = 0.044; T3 vs. T1: aOR 0.109, 95% CI 0.016-0.737, p = 0.023) and CSVD burden (T3 vs. T1: aOR 0.576, 95% CI 0.362-0.915, p = 0.019). The independent relationship between Lp(a) levels and individual CSVD features was significant for moderate-to-severe EPVS in the centrum semiovale (T2 vs. T1: aOR 0.059, 95% CI 0.006-0.542, p = 0.012; T3 vs. T1: aOR 0.029, 95% CI 0.003-0.273, p = 0.002) and CMBs (T3 vs. T1: aOR 0.144, 95% CI 0.029-0.716, p = 0.018). CONCLUSIONS: In this study, serum Lp(a) level was inversely associated with CSVD in AD patients.