Low caveolin-1 levels and symptomatic intracranial haemorrhage risk in large-vessel occlusive stroke patients after endovascular thrombectomy.

BACKGROUND AND PURPOSE: Caveolin-1 (Cav-1) is reported to mediate blood-brain barrier integrity after ischaemic stroke. Our purpose was to assess the role of circulating Cav-1 levels in predicting symptomatic intracranial haemorrhage (sICH) amongst ischaemic stroke patients after endovascular thrombectomy (EVT). METHODS: Patients with large-vessel occlusive stroke after EVT from two stroke centres were prospectively included. Serum Cav-1 level was tested after admission. sICH was diagnosed according to the Heidelberg Bleeding Classification. RESULTS: Of 325 patients (mean age 68.6 years; 207 men) included, 47 (14.5%) were diagnosed with sICH. Compared with patients without sICH, those with sICH had a lower concentration of Cav-1. After adjusting for potential confounders, multivariate regression analysis demonstrated that the increased Cav-1 level was associated with a lower sICH risk (odds ratio 0.055; 95% confidence interval 0.005-0.669; p = 0.038). Similar results were obtained when Cav-1 levels were analysed as a categorical variable. Using a logistic regression model with restricted cubic splines, a linear and negative association of Cav-1 concentration was found with sICH risk (p = 0.001 for linearity). Furthermore, the performance of the conventional risk factors model in predicting sICH was substantially improved after addition of the Cav-1 levels (integrated discrimination index 2.7%, p = 0.002; net reclassification improvement 39.7%, p = 0.007). CONCLUSIONS: Our data demonstrate that decreased Cav-1 levels are related to sICH after EVT. Incorporation of Cav-1 into clinical decision-making may help to identify patients at a high risk of sICH and warrants further consideration.

Trajectories of stroke severity and functional outcomes after endovascular treatment in ischemic stroke: A post hoc analysis of a randomized controlled trial.

BACKGROUND: The trajectory of early neurological changes in patients with acute ischemic stroke has been understudied. This study aimed to investigate the association between longitudinal trajectories of stroke severity and 90-day functional outcomes in patients with acute ischemic stroke receiving endovascular treatment. METHODS: We enrolled patients from a prospective, multicenter, randomized controlled trial. The stroke severity was assessed with the National Institute of Health Stroke Scale at the pre-procedure, 24 hours, and seven days after the procedure. Group-based trajectory modeling (GBTM) was used to identify trajectories of stroke severity. Multivariable logistic regression was performed to explore the association between stroke severity markers and 90-day functional outcomes. RESULTS: Of 218 enrolled patients, 127 (58.3%) had poor functional outcomes at 90 days. We identified three trajectories of stroke severity in the GBTM: stable symptom (38.1%), symptom deterioration (17.0%), and symptom improvement (44.9%). In multivariable analyses, trajectories of stroke severity were associated with an increased risk of poor functional outcomes (symptom improvement versus symptom deterioration: odds ratio, 0.007; 95% confidence interval, 0.001-0.040; P <0.001). Reclassification indexes revealed that trajectories of stroke severity would increase the predictive ability for poor functional outcomes at 90 days. CONCLUSION: After endovascular treatment, patients would follow one of three distinct trajectories of stroke severity. Symptom deterioration trajectory was associated with an increased risk of poor functional outcomes at 90 days. TRIAL REGISTRATION NUMBER: NCT04973332.

Emerging regulatory mechanisms in cardiovascular disease: Ferroptosis.

Ferroptosis, distinct from apoptosis, necrosis, autophagy, and other types of cell death, is a novel iron-dependent regulated cell death characterized by the accumulation of lipid peroxides and redox imbalance with distinct morphological, biochemical, and genetic features. Dysregulation of iron homeostasis, the disruption of antioxidative stress pathways and lipid peroxidation are crucial in ferroptosis. Ferroptosis is involved in the pathogenesis of several cardiovascular diseases, including atherosclerosis, cardiomyopathy, myocardial infarction, ischemia-reperfusion injury, abdominal aortic aneurysm, aortic dissection, and heart failure. Therefore, a comprehensive understanding of the mechanisms that regulate ferroptosis in cardiovascular diseases will enhance the prevention and treatment of these diseases. This review discusses the latest findings on the molecular mechanisms of ferroptosis and its regulation in cardiovascular diseases, the application of ferroptosis modulators in cardiovascular diseases, and the role of traditional Chinese medicines in ferroptosis regulation to provide a comprehensive understanding of the pathogenesis of cardiovascular diseases and identify new prevention and treatment options.

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.

Detecting prokaryote-specific gene and other bacterial signatures in thrombi from patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: Microbial infection has been associated with thrombogenesis. This study aimed to detect bacterium-specific genes and other signatures in thrombi from patients with acute ischemic stroke and to relate these signatures to clinical characteristics. METHODS: Blood samples were collected before thrombectomy procedures, and thrombus samples were obtained during the procedure. Identification and classification of bacteria in the samples were accomplished using 16 S rRNA gene sequencing. Bacterium-specific structures were observed with transmission electron microscopy. Bacterium-specific biomarkers were detected through immunohistochemical staining. RESULTS: 16 S rRNA gene was detected in 32.1% of the thrombus samples from 81 patients. Bacillus (0.04% vs. 0.00046%, p = 0.003), Parabacteroides (0.20% vs. 0.09%, p = 0.029), Prevotella (1.57% vs. 0.38%, p = 0.010), Streptococcus (1.53% vs. 0.29%, p = 0.001), Romboutsia (0.18% vs. 0.0070%, p = 0.029), Corynebacterium (1.61% vs. 1.26%, p = 0.026) and Roseburia (0.53% vs. 0.05%, p = 0.005) exhibited significantly higher abundance in thrombi compared to arterial blood. Bacteria-like structures were observed in 22 (27.1%), while whole bacteria-like structures were observed in 7 (8.6%) thrombi under transmission electron microscopy. Immunohistochemical staining detected bacterium-specific monocyte/macrophage markers in 51 (63.0%) out of 81 thrombi. Logistic regression analysis indicated that alcohol consumption was associated with a higher bacteria burden in thrombi (odds ratio = 3.19; 95% CI, 1.10-9.27; p = 0.033). CONCLUSION: Bacterial signatures usually found in the oral cavity and digestive tract were detected in thrombi from patients with ischemic stroke. This suggests a potential involvement of bacterial infection in the development of thrombosis. Long-term alcohol consumption may potentially enhance this possibility.

Association between liver fibrosis and stroke recurrence in young patients with ischemic stroke.

BACKGROUND AND AIM: Stroke incidence rates are rising among young adults. Liver fibrosis has recently been recognized as a risk factor for cardiovascular events and stroke in the general population. It remains unclear whether liver fibrosis influences the prognosis of stroke. We aimed to evaluate the association between liver fibrosis and stroke recurrence in young stroke patients. METHODS AND RESULTS: Young adults with first-ever ischemic stroke were enrolled from a prospective stroke registry and were followed up for stroke recurrence. Liver fibrosis was evaluated by Fibrosis-4 (FIB-4) score and was stratified into three categories. Cox regression analysis was performed to assess the relationship between liver fibrosis and stroke recurrence. Over a median follow-up of 3.1 (1.7-4.6) years, 72 (11.6%) recurrent strokes occurred among 621 patients. According to the FIB-4 score, 73 (11.7%) patients had indeterminate fibrosis, while 11 (1.8%) had advanced fibrosis. Univariate Cox analysis revealed that patients with a high FIB-4 score were more likely to experience stroke recurrence than those with a low FIB-4 score (hazard ratio 3.748, 95% confidence interval 1.359-10.332, P = 0.011). After adjusting for potential confounders in the multivariate analysis, FIB-4 score remained an independent risk factor. CONCLUSIONS: Young stroke patients with advanced liver fibrosis were at a greater risk of stroke recurrence. Evaluating liver fibrosis may provide valuable information for stroke risk stratification, and the FIB-4 score could serve as a useful tool.

The establishment and application of a dual Nano-PCR detection method for feline calicivirus and feline herpesvirus type I.

Feline calicivirus (FCV) and Feline herpesvirus type I (FHV-I) are the main pathogens causing upper respiratory tract infections in cats, and some wild animals. These two viruses always coinfection and cause serious harm to pet industry and wild animals protection. Established a rapid and accurate differential diagnosis method is crucial for prevention and control of disease, however, the current main detection method for these two viruses, either is low sensitivity (immunochromatographic strip), or is time-consuming and cannot differential diagnosis (conventional single PCR). Nanoparticle-assisted polymerase chain reaction (Nano-PCR) is a recently developed technique for rapid detection method of virus and bacteria. In this study, we described a dual Nano-PCR assay through combining the nanotechnology and PCR technology, which for the clinical simultaneous detection of FCV and FHV-I and differential diagnosis of upper respiratory tract infections in cats or other animals. Under optimized conditions, the optimal annealing temperature for dual Nano-PCR was 51.5°C, and specificity test results showed it had no cross reactivity to related virus, such as feline panleukopenia virus (FPV), feline Infectious peritonitis virus (FIPV) and rabies virus (RABV). Furthermore, the detection limit of dual Nano-PCR for FCV and FHV-I both were 1 × 10-8 ng/µL, convert to number of copies of virus DNA was 6.22 × 103copies/µL (FCV) and 2.81 × 103copies/µL (FHV-I), respectively. The dual Nano-PCR detected result of 52 cat clinical samples, including ocular, nasal and faecal swabs, and (3 FCV-positive samples), was consistent with ordinary PCR and the clinical detection results. The dual Nano-PCR method established in this study with strong specificity and high sensitivity can be used for virus nucleic acid (FCV and FHV-I) detection of clinical samples of feline upper respiratory tract infections feline calicivirus and feline herpesvirus while providing support for the early diagnosis of cats that infected by FCV and FHV-I.

Discrimination for geographical origin of Panax quinquefolius L. using UPLC Q-Orbitrap MS-based metabolomics approach.

American ginseng, Panax quinquefolius L., is an important medicinal plant with multiple pharmacological effects and high nutritional value. American ginseng from different geographical origins varies in quality and price. However, there was no approach for discriminating American ginseng from different geographical origins to date. In this study, a metabolomic method based on the UPLC-Orbitrap fusion platform was established to comprehensively determine and analyze metabolites of American ginseng from America and Canada, Heilongjiang, Jilin, Liaoning, and Shandong provinces in China. A total of 382 metabolites were detected, including 230 saponins, 30 amino acids and derivatives, 27 organic acids and derivatives, 25 lipids, 17 carbohydrates and derivatives, 10 phenols, 8 nucleotides, and derivatives, as well as 35 other metabolites. Metabolite differences between North America and Asia producing areas were more obvious than within Asia. Twenty metabolites, contributed most to the differentiation of producing areas, were identified as potential markers with prediction accuracy higher than 91%. The results provide new insights into the metabolite composition of American ginseng from different origins, which will help discriminate origins and promote quality control of American ginseng.

Association between Citrullinated Histone H3 and White Matter Lesions Burden in Patients with Ischemic Stroke.

INTRODUCTION: Neutrophil extracellular traps play a role in the pathophysiology of stroke and are associated with severity and mortality. We aimed to investigate whether the citrullinated histone H3 (CitH3), a biomarker for neutrophil extracellular traps formation, is associated with the white matter lesion (WML) burden in ischemic stroke patients. METHODS: Between September 2021 and April 2022, 322 patients were enrolled in this prospective observational cohort study. Serum CitH3 levels were measured after admission using an enzyme-linked immunosorbent assay. WMLs severity was graded according to the Fazekas scale and conceptually defined as mild (total Fazekas score 0-2) and severe (total Fazekas score 3-6). We used multivariable regression models to determine the relationship between CitH3 concentrations and the severity of WMLs burden. RESULTS: One-hundred and forty-eight (46.0%) patients were diagnosed with severe WMLs burden after admission. Increased CitH3 levels (first quartile vs. fourth quartile of H3Cit, odds ratio, 3.311, 95% confidence interval, 1.336-8.027; p = 0.011) were independently associated with a greater WML burden in the fully adjusted multivariable model. Similar results were found when the H3Cit was analyzed as a continuous variable. Furthermore, the multiple-adjusted spline regression model showed a linear association between H3Cit levels and severe WMLs (P = 0.001 for linearity). CONCLUSIONS: In the present study, increased CitH3 levels were positively associated with extensive WMLs in ischemic stroke patients, indicating a role of neutrophil extracellular traps formation in the pathogenesis of WMLs.

Association Between Inflammatory Burden Index and Unfavorable Prognosis After Endovascular Thrombectomy in Acute Ischemic Stroke.

Background: Inflammatory burden index (IBI) is a systemic inflammation indicator that reflects the inflammatory status. We aimed to investigate the prognostic value of IBI after endovascular thrombectomy (EVT) in patients with acute ischemic stroke. Methods: We enrolled patients treated with EVT from a multicenter cohort between June 2020 and December 2021. The IBI was calculated as C-reaction protein × neutrophil / lymphocyte count. The primary outcome was the unfavorable functional outcome (90-day modified Rankin scale score 3-6). C-statistics and net reclassification indexes were used to assess the predictive accuracy. Multivariable logistic regression models were used to investigate the association between IBI and unfavorable outcome. Results: A total of 295 patients (mean age, 64.0 ± 12.8 years; male, 63.7%) were enrolled in this study. In multivariable models, higher IBI levels were associated with an increased risk of 90-day unfavorable outcome after EVT (per 1-SD: odds ratio, 1.754; 95% confidence interval, 1.241-2.587; P = 0.002). Restricted cubic spline curve displayed a linear relationship between the IBI level and 90-day unfavorable outcome (P for nonlinearity = 0.410). Besides, IBI was a more accurate biomarker for predicting unfavorable outcomes with the highest predictive accuracy and reclassification indexes. Conclusion: This study demonstrated that higher IBI was associated with an increased risk of 90-day unfavorable outcome in acute ischemic stroke treated with EVT.

Association of glycemic gap with stroke recurrence in patients with ischemic stroke.

BACKGROUND: Glycemic gap, as a novel index of acute glycemic excursion, is associated with poor prognosis of different diseases. This study aimed to explore the association of the glycemic gap with long-term stroke recurrence in patients with ischemic stroke. METHODS: This study included patients with ischemic stroke from the Nanjing Stroke Registry Program. The glycemic gap was calculated by subtracting the estimated average blood glucose from the blood glucose at admission. Multivariable Cox proportional hazards regression analysis was performed to explore the association between the glycemic gap and the risk of stroke recurrence. The Bayesian hierarchical logistic regression model was used to estimate the effects of the glycemic gap on stroke recurrence stratified by diabetes mellitus and atrial fibrillation. RESULTS: Among 2734 enrolled patients, 381 (13.9%) patients experienced stroke recurrence during a median follow-up of 3.02 years. In multivariate analysis, glycemic gap (high group vs. median group) was associated with significantly increased risk for stroke recurrence (adjusted hazard ratio, 1.488; 95% confidence interval, 1.140-1.942; p = .003) and had varying effects on stroke recurrence depending on atrial fibrillation. The restricted cubic spline curve showed a U-shaped relationship between the glycemic gap and stroke recurrence (p = .046 for nonlinearity). CONCLUSION: Our study found that the glycemic gap was significantly associated with stroke recurrence in patients with ischemic stroke. The glycemic gap was consistently associated with stroke recurrence across subgroups and had varying effects depending on atrial fibrillation.

Lipocalin-2-mediated astrocyte pyroptosis promotes neuroinflammatory injury via NLRP3 inflammasome activation in cerebral ischemia/reperfusion injury.

BACKGROUND: Neuroinflammation is a vital pathophysiological process during ischemic stroke. Activated astrocytes play a major role in inflammation. Lipocalin-2 (LCN2), secreted by activated astrocytes, promotes neuroinflammation. Pyroptosis is a pro-inflammatory form of programmed cell death that has emerged as a new area of research in stroke. Nevertheless, the potential role of LCN2 in astrocyte pyroptosis remains unclear. METHODS: An ischemic stroke model was established by middle cerebral artery occlusion (MCAO) in vivo. In this study, in vitro, oxygen-glucose deprivation and reoxygenation (O/R) were applied to cultured astrocytes. 24p3R (the LCN2 receptor) was inhibited by astrocyte-specific adeno-associated virus (AAV-GFAP-24p3Ri). MCC950 and Nigericin sodium salt (Nig) were used to inhibit or promote the activation of NLRP3 inflammasome pharmacologically, respectively. Histological and biochemical analyses were performed to assess astrocyte and neuron death. Additionally, the neurological deficits of mice were evaluated. RESULTS: LCN2 expression was significantly induced in astrocytes 24 h after stroke onset in the mouse MCAO model. Lcn2 knockout (Lcn2-/-) mice exhibited reduced infarct volume and improved neurological and cognitive functions after MCAO. LCN2 and its receptor 24p3R were colocalized in astrocytes. Mechanistically, suppression of 24p3R by AAV-GFAP-24p3Ri alleviated pyroptosis-related pore formation and the secretion of pro-inflammatory cytokines via LCN2, which was then reversed by Nig-induced NLRP3 inflammasome activation. Astrocyte pyroptosis was exacerbated in Lcn2-/- mice by intracerebroventricular administration of recombinant LCN2 (rLCN2), while this aggravation was restricted by blocking 24p3R or inhibiting NLRP3 inflammasome activation with MCC950. CONCLUSION: LCN2/24p3R mediates astrocyte pyroptosis via NLRP3 inflammasome activation following cerebral ischemia/reperfusion injury.

The metabolic score for insulin resistance as a predictor of clinical outcome in stroke patients treated by intravenous thrombolysis.

BACKGROUND AND PURPOSE: Insulin resistance is associated with clinical outcomes among patients with ischemic stroke. We aimed to investigate the association between metabolic score for insulin resistance (METS-IR) and clinical outcomes in stroke patients treated by intravenous thrombolysis (IVT). METHODS: We recruited participants treated with IVT from a prospective registry including 3 stroke centers. Poor outcome was defined as a modified Rankin scale score ≥ 3 points at 90 days after the index stroke. We performed logistic regression models to investigate the association between METS-IR and the risk of poor outcome. We used the receiver operative characteristic to assess the discriminative ability and the restricted cubic spline to explore the relationship between METS-IR and the poor outcome. RESULTS: This study enrolled a total of 1074 patients (median age, 68; 63.8% male). Three hundred sixty (33.5%) patients had poor outcome after IVT. METS-IR was associated with the risk of the poor outcome with the increase of confounding factors in models (odds ratio [OR], 1.078; 95% confidence interval [CI], 1.058-1.099; P < 0.001). The area under the curve for METS-IR for predicting the poor outcome was 0.790 (95% CI, 0.761-0.819). The restricted cubic spline revealed an increasing and non-linear association between METS-IR and the poor outcome (P for non-linearity < 0.001). CONCLUSION: Our study found that METS-IR was associated with an increased risk of poor outcome after IVT. Further studies are warranted to investigate the efficacy of anti-diabetic agents regarding IR on clinical outcomes after IVT.

Systemic Immune-Inflammation Index and Long-Term Mortality in Patients with Stroke-Associated Pneumonia.

Background: Systemic immune inflammation has been investigated as a prognostic marker of different diseases. This study is designed to assess the association of systemic immune-inflammation index (SII) with long-term mortality of stroke-associated pneumonia (SAP) patients. Methods: Patients aged ≥18 years with SAP were selected from the Nanjing Stroke Registry Program in China. We retrospectively evaluated systemic immune-inflammation response with SII and pneumonia severity with the pneumonia severity index and the confusion, uremia, elevated respiratory rate, hypotension, and aged 65 years or older score. To explore the correlation between SII and mortality in SAP patients, multivariable Cox regressions and competing risk regressions were conducted. Mediation analysis was also performed to assess the role of pneumonia severity. Results: Among 611 patients in the SAP population, death occurred in 164 patients (26.8%) during the median follow-up of 3.0 (1.2-4.6) years. In multivariate analysis, higher SII scores could predict increased mortality in patients with SAP (adjusted hazard ratio 2.061; 95% confidence interval, 1.256-3.383; P = 0.004), and the association was mediated by pneumonia severity. Moreover, adding SII to traditional models improved their predictive ability for mortality. Conclusion: Our study displayed that SII was characterized in SAP patients with different prognoses. Elevated SII scores increased the risk of mortality. Further research is required for the clinical practice of the index among SAP patients.

Circulating lipocalin-2 as a novel biomarker for early neurological deterioration and unfavorable prognosis after acute ischemic stroke.

INTRODUCTION: Lipocalin-2 (LCN2) is an acute-phase protein that could mediate neuroinflammation after brain injury. We aimed to evaluate if LCN2 level was associated with early neurological deterioration (END) in acute ischemic stroke patients, thus hindering clinical recovery. METHODS: We conducted a prospective study of acute ischemic stroke patients between June 2021 and February 2022. Serum LCN2 concentration was measured after admission using an enzyme-linked immunosorbent assay. Outcomes included END and 90-day poor functional outcome (modified Rankin Scale 3-6). The National Institutes of Health Stroke Scale increment ≥4 points within 72 h after admission was defined as END. RESULTS: A total of 253 acute ischemic stroke patients (mean age, 65.2 ± 13.4 years; 64.0% male) were recruited. In the multivariate adjustment, increased serum LCN2 levels (per 1-SD increase of LCN2) were associated with a higher risk of END (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.20-2.25; p = .002) and 90-day poor outcome (OR, 1.73; 95% CI, 1.22-2.45; p = .002). Restricted cubic splines found a linear relationship between LCN2 level and 90-day unfavorable outcome (END, p = .001 for linearity; 90-day poor outcome, p = .013 for linearity). Subgroup analysis further confirmed the significant association of LCN2 with clinical outcomes. CONCLUSIONS: This study demonstrated that higher circulating LCN2 level was associated with an increased risk of early clinical worsening and 90-day unfavorable outcomes in ischemic stroke patients.

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.

Impacts of stress hyperglycemia ratio on early neurological deterioration and functional outcome after endovascular treatment in patients with acute ischemic stroke.

Background and Purpose: Hyperglycemia has been associated with unfavorable outcome of acute ischemic stroke, but this association has not been verified in patients with endovascular thrombectomy treatment. This study aimed to assess the impact of stress hyperglycemia ratio on early neurological deterioration and favorable outcome after thrombectomy in patients with acute ischemic stroke. Methods: Stroke patients with endovascular thrombectomy in two comprehensive centers were enrolled. Early neurological deterioration was defined as ≥4 points increase of National Institutes of Health Stroke Scale (NIHSS) at 24 hours after endovascular procedure. Favorable outcome was defined as modified Rankin Scale (mRS) score of 0-2 at 90 days of stroke onset. Multivariate regression analysis was used to identify the predictors for early neurological deterioration and favorable outcome. Results: Among the 559 enrolled, 74 (13.2%) patients developed early neurological deterioration. The predictors for early neurological deterioration were high stress hyperglycemia ratio at baseline (OR =5.77; 95% CI, 1.878-17.742; P =0.002), symptomatic intracranial hemorrhage (OR =4.90; 95% CI, 2.439-9.835; P <0.001) and high NIHSS score after 24 hours (OR =1.11; 95% CI, 1.071-1.151; P <0.001). The predictors for favorable outcome were stress hyperglycemia ratio (OR =0.196, 95% CI, 0.077-0.502; P =0.001), age (OR =0.942, 95% CI, 0.909-0.977; P =0.001), NIHSS score 24 hours after onset (OR =0.757, 95% CI =0.693-0.827; P <0.001), groin puncture to recanalization time (OR =0.987, 95% CI, 0.975-0.998; P =0.025), poor collateral status before treatment (ASITN/SIR grade 0-3, OR =62.017, 95% CI, 25.920-148.382; P <0.001), successful recanalization (mTICI 2b or 3, OR =7.415, 95% CI, 1.942-28.313; P =0.001). Conclusion: High stress hyperglycemia ratio may be related to early neurological deterioration and decreased likelihood of favourable outcomes after endovascular thrombectomy in patients with acute ischemic stroke.

A Novel Metabolic Score for Insulin Resistance and Symptomatic Intracranial Hemorrhage in Ischemic Stroke Patients After Endovascular Thrombectomy.

Background and Purpose: Insulin resistance plays a pivotal role in the pathophysiology of ischemic stroke. This study aimed to determine the relationship between the novel metabolic score for insulin resistance (METS-IR) and symptomatic intracranial hemorrhage (sICH) after endovascular thrombectomy (EVT) in stroke patients. Methods: We retrospectively included patients with large artery occlusion in the anterior circulation and treated by EVT from 2 stroke centers (Nanjing First Hospital from September 2019 to April 2022, and Jinling Hospital from September 2019 to July 2021). The METS-IR was used as an alternative marker of insulin resistance and calculated using laboratory data after admission. sICH was diagnosed according to the Heidelberg Bleeding Classification. Results: Of the 410 enrolled patients (mean age, 69.8 ± 11.7 years; 60.7% men), 50 (12.2%) were diagnosed as sICH. After adjusting for demographic characteristics, poor collateral status, and other potential confounders, higher METS-IR was revealed to be independently associated with sICH (odds ratio, 1.076; 95% confidence interval, 1.034-1.120; P = 0.001). Similar significant results were obtained when defining METS-IR as a categorical variable. The restricted cubic spline uncovered a linear relationship between METS-IR and sICH (P < 0.001 for linearity). Furthermore, adding METS-IR to the conventional model significantly improved the risk prediction for sICH (net reclassification improvement = 15.8%, P = 0.035; integrated discrimination index = 2.6%; P = 0.017). Conclusion: This study demonstrated a significant association between METS-IR score and sICH in ischemic stroke patients treated with EVT. It could help monitor and manage sICH in patients after EVT.

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.

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.