Association of plasma VEGF with futile recanalization and intracranial angiogenesis in ischemic stroke post-endovascular treatment.

This study aimed to compare baseline and subsequent vascular endothelial growth factor (VEGF) levels in predicting futile recanalization (FR) in acute ischemic stroke (AIS) patients undergoing endovascular treatment (EVT), and to explore the association between angiogenesis and VEGF. 84 participants were recruited, including 46 AIS in the EVT group, 20 AIS in the conventional treatment group, and 18 healthy controls. Plasma VEGF levels were measured at different time points. FR was defined as a modified Rankin scale score of 3-6 at 3 months. Multivariable analysis evaluated whether VEGF levels at different time points independently predicted FR, and receiver operating characteristic (ROC) curves assessed their predictive value. Using intracranial lesion side vascular imaging, the Maas scoring system assessed angiogenesis post-onset, with scores of 4 to 5 indicating angiogenesis. In the conventional treatment group, VEGF levels significantly decreased by day 7, while in the EVT group, reduction was observed as early as day 3. After adjusting for potential confounders, only VEGF levels on day 3 emerged as an independent predictor of FR. The combined model incorporating VEGF levels on day 3 with other factors effectively predicted FR (area under the curve = 0.916; sensitivity = 84.21 %; specificity = 100 %, P<0.0001). Plasma VEGF levels were notably higher in patients with angiogenesis in specific brain regions compared to those without angiogenesis at days 1, 3, 7, and 14 (P<0.05). VEGF levels on the 3rd day post-EVT demonstrate superior predictive value for FR. Elevated VEGF levels correlate with angiogenesis, suggesting its potential as a therapeutic target.

Xu B ，Wu Z ，Lin Y ，Liu Y ，Liu L ，Zhang Y ... -  《-》

Predictors of futile recanalization after endovascular treatment of acute ischemic stroke.

Endovascular therapy (EVT) is the most successful treatment for patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) in the anterior circulation. However, futile recanalization (FR) seriously affects the prognosis of these patients. The aim of this study was to investigate predictors of FR after EVT in patients with AIS. Patients diagnosed with AIS due to anterior circulation LVO and receiving EVT between June 2020 and October 2022 were prospectively enrolled. FR after EVT was defined as a poor 90-day prognosis (modified Rankin Scale [mRS] score ≥ 3) despite achieving successful reperfusion (modified Thrombolysis in Cerebral Infarction [mTICI] classification of 2b-3). All included patients were categorized into control group (mRS score < 3) and FR group (mRS score ≥ 3). Demographic characteristics, comorbidities (hypertension, diabetes, atrial fibrillation, smoking, etc.), stroke-specific data (NIHSS score, ASPECT score and site of occlusion), procedure data (treatment type [direct thrombectomy vs. bridging thrombectomy], degree of vascular recanalization [mTICI], procedure duration time and onset-recanalization time), laboratory indicators (lymphocytes count, neutrophils count, monocytes count, C-reactive protein, neutrophil-to-lymphocyte ratio [NLR], monocyte-to-high-density lipoprotein ratio [MHR], lymphocyte-to-monocyte ratio [LMR], lymphocyte-to-C-reactive protein ratio [LCR], lymphocyte-to-high-density lipoprotein ratio[LHR], total cholesterol and triglycerides.) were compared between the two groups. Multivariate logistic regression analysis was performed to explore independent predictors of FR after EVT. A total of 196 patients were included in this study, among which 57 patients were included in the control group and 139 patients were included in the FR group. Age, proportion of patients with hypertension and diabetes mellitus, median NIHSS score, CRP level, procedure duration time, neutrophil count and NLR were higher in the FR group than in the control group. Lymphocyte count, LMR, and LCR were lower in the FR group than in the control group. There were no significant differences in platelet count, monocytes count, total cholesterol, triglycerides, HDL, LDL, gender, smoking, atrial fibrillation, percentage of occluded sites, onset-recanalization time, ASPECT score and type of treatment between the two groups. Multivariate logistic regression analysis demonstrated that NLR was independently associated with FR after EVT (OR = 1.37, 95%CI = 1.005-1.86, P = 0.046). This study demonstrated that high NLR was associated with a risk of FR in patients with AIS due to anterior circulation LVO. These findings may help clinicians determine which patients with AIS are at higher risk of FR after EVT. Our study can provide a theoretical basis for interventions in the aforementioned population.

Wang LR ，Li BH ，Zhang Q ，Cheng XD ，Jia LJ ，Zhou S ，Yang S ，Wang JH ，Yu NW ... -  《BMC Neurology》

Futile recanalization after endovascular treatment in acute ischemic stroke with large ischemic core.

Endovascular therapy (EVT) is the treatment of choice for acute ischemic stroke (AIS) with large vessel occlusion. However, in many patients, successful EVT recanalization does not correspond to a clinical improvement, called futile recanalization (FR). We aimed to identify stroke risk factors and patient characteristics associated with FR in AIS with large core infarct (LCI). A total of 137 patients with AIS with LCI treated by EVT at a single stroke center were retrospectively included from January 2016 to June 2023. LCI was defined by Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECT) < 6. Patient age, sex, modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS), time to treatment, risk factors, and radiologic findings were collected, and potential associations with FR were analyzed. FR was defined as successful reperfusion with modified Thrombolysis in Cerebral Infarction (mTICI) ≥ 2b but without functional independence at 90 days (mRS ≥ 3). A multivariate logistic regression analysis was conducted on the clinical characteristics of patients, based on the presence or absence of FR, and the factors influencing FR. Of 137 patients, 120 showed successful recanalization (mTICI ≥ 2b). All patients were divided into FR (n = 80) and no FR (n = 40) groups. Older age (odds ratio [OR] 1.052, 95% confidence interval [CI] 1.002-1.105; p = 0.041), the higher the initial NIHSS score (OR 1.181, 95% CI 1.037-1.344; p = 0.012), and prior intravenous plasminogen activator (OR 0.310, 95% CI 0.118-0.813, p = 0.017) were independent influencing factors of FR. The older age, the higher the initial NIHSS, and not receiving intravenous plasminogen activator were independently associated with FR in AIS with LCI. These factors could identify poor responders to EVT recanalization.

Kim H ，Kim JT ，Choi KH ，Yoon W ，Baek BH ，Kim SK ，Kim YS ，Kim TS ，Park MS ... -  《BMC Neurology》

Cystatin C predicts futile recanalization in patients with acute ischemic stroke after endovascular treatment.

A previous study reported that cystatin C was related to acute ischemic stroke. The association between cystatin C and the clinical outcome in acute ischaemic stroke patients with successful recanalization after endovascular thrombectomy has rarely been reported. This study aimed to evaluate the association between cystatin C and futile recanalization in AIS patients who underwent endovascular thrombectomy. We carried out a retrospective study of acute ischaemic stroke patients with anterior circulation proximal arterial occlusion who achieved complete arterial recanalization after mechanical thrombectomy from May 2017 to April 2020. The patients with complete recanalization were divided into a useful recanalization group and a futile recanalization group according to their 3-month modified Rankin scale score. FR was defined as a modified mRS score of 3-6 at 3 months. Logistic regression analysis was used to identify the risk factors for FR. Receiver operating characteristic curves were used to assess the predictive value of cystatin C for FR. Of 241 patients, 125 underwent futile recanalization and 116 underwent useful recanalization. Baseline serum cystatin C levels were higher in the futile recanalization group than in the useful recanalization group. After adjustment for potential confounding factors, multivariable adjusted regression models showed that cystatin C was an independent predictor of futile recanalization (odds ratio, 4.111 [95% CI 1.427-11.840], P = 0.009). Receiver operator characteristic (ROC) curve analysis indicated that the model combining cystatin C with other factors model effectively predicted unfavourable outcomes at 3 months (area under the curve = 0.782, p < 0.01). A higher level of cystatin C is associated with unfavourable outcomes at 3 months in anterior circulation acute ischaemic stroke patients with endovascular thrombectomy.

Su M ，Zhou Y ，Chen Z ，Pu M ，Li Z ，Du H ，Xu G ... -  《-》

Plasma Lipid Mediators Associate With Clinical Outcome After Successful Endovascular Thrombectomy in Patients With Acute Ischemic Stroke.

Neuroinflammatory response contributes to early neurological deterioration (END) and unfavorable long-term functional outcome in patients with acute ischemic stroke (AIS) who recanalized successfully by endovascular thrombectomy (EVT), but there are no reliable biomarkers for their accurate prediction. Here, we sought to determine the temporal plasma profiles of the bioactive lipid mediators lipoxin A4 (LXA4), resolvin D1 (RvD1), and leukotriene B4 (LTB4) for their associations with clinical outcome. We quantified levels of LXA4, RvD1, and LTB4 in blood samples retrospectively and longitudinally collected from consecutive AIS patients who underwent complete angiographic recanalization by EVT at admission (pre-EVT) and 24 hrs post-EVT. The primary outcome was unfavorable long-term functional outcome, defined as a 90-day modified Rankin Scale score of 3-6. Secondary outcome was END, defined as an increase in National Institutes of Health Stroke Scale (NIHSS) score ≥4 points at 24 hrs post-EVT. Eighty-one consecutive AIS patients and 20 healthy subjects were recruited for this study. Plasma levels of LXA4, RvD1, and LTB4 were significantly increased in post-EVT samples from AIS patients, as compared to those of healthy controls. END occurred in 17 (20.99%) patients, and 38 (46.91%) had unfavorable 90-day functional outcome. Multiple logistic regression analyses demonstrated that post-EVT levels of LXA4 (adjusted odd ratio [OR] 0.992, 95% confidence interval [CI] 0.987-0.998), ΔLXA4 (adjusted OR 0.995, 95% CI 0.991-0.999), LTB4 (adjusted OR 1.003, 95% CI 1.001-1.005), ΔLTB4 (adjusted OR 1.004, 95% CI 1.002-1.006), and post-EVT LXA4/LTB4 (adjusted OR 0.023, 95% CI 0.001-0.433) and RvD1/LTB4 (adjusted OR 0.196, 95% CI 0.057-0.682) ratios independently predicted END, and post-EVT LXA4 levels (adjusted OR 0.995, 95% CI 0.992-0.999), ΔLXA4 levels (adjusted OR 0.996, 95% CI 0.993-0.999), and post-EVT LXA4/LTB4 ratio (adjusted OR 0.285, 95% CI 0.096-0.845) independently predicted unfavorable 90-day functional outcome. These were validated using receiver operating characteristic curve analyses. Plasma lipid mediators measured 24 hrs post-EVT were independent predictors for early and long-term outcomes. Further studies are needed to determine their causal-effect relationship, and whether the imbalance between anti-inflammatory/pro-resolving and pro-inflammatory lipid mediators could be a potential adjunct therapeutic target.

Hao J ，Feng Y ，Xu X ，Li L ，Yang K ，Dai G ，Gao W ，Zhang M ，Fan Y ，Yin T ，Wang J ，Yang B ，Jiao L ，Zhang L ... -  《Frontiers in Immunology》