SLC44A2-mediated phenotypic switch of vascular smooth muscle cells contributes to aortic aneurysm.

The phenotypic switch of vascular smooth cells (VSMCs) from a contractile to a synthetic state is associated with the development and progression of aortic aneurysm (AA). However, the mechanism underlying this process remains unclear. In this issue of the JCI, Song et al. identified SLC44A2 as a regulator of the phenotypic switch in VSMCs. Inhibition of SLC44A2 facilitated the switch to the synthetic state, contributing to the development of AA. Mechanistically, SLC44A2 interacted with NRP1 and ITGB3 to activate the TGF-ß/SMAD signaling pathway, resulting in VSMCs with a contractile phenotype. Furthermore, VSMC-specific SLC44A2 overexpression by genetic or pharmacological manipulation reduced AA in mouse models. These findings suggest the potential of targeting the SLC44A2 signaling pathway for AA prevention and treatment.

After early mTICI 2b, stop or continue? Insights from the PERSIST Registry.

OBJECTIVES: A higher reperfusion grade after endovascular thrombectomy (EVT) is associated with a good prognosis. However, the effect of the number of retrievals has not yet been investigated in vertebrobasilar occlusion (VBAO). Therefore, the aim of this study was to investigate whether to continue retrieval after early modified thrombolysis in cerebral infarction (mTICI) 2b to achieve a better reperfusion grade. METHODS: We retrospectively analyzed the data of patients who underwent EVT caused by VBAO in a multicenter registry dataset. Patients who underwent successful reperfusion were included (mTICI 2b/3). Regression models were used to analyze the correlation of different reperfusion grades stratified by the number of retrieval attempts with clinical prognosis and hemorrhage transition. RESULTS: We included 432 patients: 34.5% (n = 149) had a final mTICI score of 2b and 65.5% (n = 283) had a final mTICI score of 3. Patients who obtained a mTICI of 3 after the first pass had significantly increased odds of having a good prognosis. As the number of passes increases, the chances of obtaining a good prognosis decreases. After three or more passes, the odds of achieving functional independence and favorable outcomes were comparable to those of the first mTICI 2b, regardless of the 90-day (OR 1.132 95% CI 0.367-3.487 p = 0.829; OR 1.070 95% CI 0.375-3.047 p = 0.900) or 1-year follow-up (OR 1.217 95% CI 0.407-3.637 p = 0.725; OR 1.068 95% CI 0.359-3.173 p = 0.906). INTERPRETATION: Within two retrieval attempts, mTICI 3 was better than the first retrieval to mTICI 2b. After early mTICI 2b, each retrieval should be undertaken with caution to pursue a higher reperfusion grade.

Incidence, predictors, and outcomes of malignant cerebral edema in acute basilar artery occlusion after endovascular treatment: a secondary analysis of the ATTENTION trial.

OBJECTIVE: Malignant cerebral edema (MCE) is a life-threatening complication of ischemic stroke. Few studies have evaluated MCE in patients with acute basilar artery occlusion (BAO) receiving endovascular treatment (EVT). Therefore, the authors investigated the incidence, predictors, and functional outcomes of MCE in BAO patients undergoing EVT. METHODS: This was a post hoc analysis of the Endovascular Treatment for Acute Basilar Artery Occlusion (ATTENTION) trial, a prospective, randomized, multicenter clinical trial that compared endovascular treatment with conventional care of patients with BAO at 36 centers in China. Brain edema was retrospectively assessed using the Jauss score for all available follow-up scans, and patients with a Jauss score ≥ 4 were classified as having MCE. Clinical functional independence was defined as a modified Rankin Scale (mRS) score of 0-2, and a good outcome was defined as an mRS score of 0-3 at the 90-day follow-up. Univariate and multivariate analyses were used to explore the predictors of MCE and the impact of MCE on prognosis. RESULTS: A total of 189 patients were analyzed, and 13.2% of patients developed MCE. Multivariate analysis showed that the baseline Glasgow Coma Scale (GCS) score (OR 0.722, 95% CI 0.548-0.950; p = 0.020) and the number of procedures (OR 1.594, 95% CI 1.051-2.419; p = 0.028) were significantly associated with MCE. After adjusting for confounding factors, the presence of MCE was significantly associated with a lower rate of functional independence (OR 0.115, 95% CI 0.023-0.563; p = 0.008), a lower rate of good outcome (OR 0.092, 95% CI 0.023-0.360; p = 0.001), and a higher rate of mortality (OR 5.373, 95% CI 2.055-14.052; p = 0.001) at the 90-day follow-up. CONCLUSIONS: MCE is not uncommon in BAO patients undergoing EVT and is associated with poor outcomes. Baseline GCS score and the number of procedures were predictors of MCE. In clinical practice, it is crucial that physicians identifying MCE after EVT in patients with BAO and identification of MCE will help in the selection of an appropriate pharmacological treatment strategy and close monitoring.

Blood pressure variability and outcome in atherosclerosis versus cardioembolism cerebral large vessel occlusion after successful thrombectomy.

Higher blood pressure variability (BPV) has been proven associated with worse functional outcome after endovascular treatment (EVT). However, this association is not established according to different stroke etiologies. In this study, we compared patients with the two highest proportions of stroke etiologies-cardioembolism (CE) and large-artery atherosclerosis (LAA), aiming to explore appropriate strategies of BP management for different etiologies. We enrolled patients with large vessel occlusion (LVO) in anterior circulation who underwent EVT and achieved successful recanalization retrospectively. 24-h blood pressure (BP) and BPV measured as blood pressure reduction (BPr), standard deviation (SD), coefficient of variation (CV), successive variation (SV), average real variability (ARV) after EVT were collected for systolic blood pressure (SBP) and diastolic blood pressure (DBP). The favorable outcome was defined as functional independence by 90-day modified Rankin Scale (mRS 0-2). In our cohort, higher BPV parameters significantly resulted in 90d functional dependence in CE-LVO patients (SBPSV OR: 1.083, 95%CI = 1.009-1.163; SBPARV OR: 1.121, 95%CI = 1.019-1.233; DBPSD OR: 1.124, 95%CI = 1.007-1.1256; DBPCV OR: 1.078, 95%CI = 1.002-1.161). However, for LAA-LVO patients, no positive results correlated 90d functional dependence with 24-hour BPV. Additionally, 90d functional dependence in CE patients with poor collaterals were significantly dependent on post-procedural BPV (DBPmax OR: 1.044, 95%CI = 1.002-1.087; DBPSD OR: 1.229, 95%CI = 1.022-1.1.479; DBPCV OR: 1.143, 95%CI = 1.009-1.295). Whereas to patients with good collaterals, there did not exist such a correlation. In summary, stroke etiologies should probably be taken into consideration to optimize individualized BP management strategies. In order to achieve better clinical outcomes for patients with acute ischemic stroke due to large vessel occlusion, stricter blood pressure management should be taken in cardioembolic stroke patients in contrast with large artery atherosclerotic stroke patients after successful endovascular therapy.

New stress-induced hyperglycaemia markers predict prognosis in patients after mechanical thrombectomy.

OBJECTIVE: Stress-induced hyperglycaemia (SIH) is a frequent phenomenon that occurs in patients with acute ischaemic stroke. The aim of this study was to investigate the relationship between SIH and the prognosis of mechanical thrombectomy (MT) patients according to the stress hyperglycemia ratio (SHR) and glycaemic gap (GG) indicators, as well as explore its relationship with haemorrhagic transformation (HT). METHODS: Patients were enrolled from January 2019 to September 2021 in our centre. SHR was calculated as fasting blood glucose divided by the A1c-derived average glucose (ADAG). GG was calculated as fasting blood glucose minus ADAG. Logistic regression was used to analyse SHR, GG with outcome and HT. RESULTS: A total of 423 patients were enrolled in the study. The incidence of SIH was as follows: 191/423 of patients with SHR > 0.89, 169/423 of patients with GG > -0.53. SHR > 0.89 (OR: 2.247, 95% CI: 1.344-3.756, P = 0.002) and GG>-0.53 (OR: 2.305, 95% CI: 1.370-3.879, P = 0.002) were both associated with poor outcomes (modified Rankin Scale > 2) at Day 90 and an increase risk of HT. Additionlly, receiver operating characteristic curves were used to assess the predictive performance of the SHR and GG on outcomes. The area under the curve for SHR to predict poor outcomes was 0.691, with an optimal cut-off value of 0.89. The area under the curve for GG was 0.682, with an optimal cut-off value of -0.53. CONCLUSION: High SHR and high GG are strongly associated with poor 90-day prognosis in MT patients and an increased risk of HT.

Effect of prolonged microcirculation time after thrombectomy on the outcome of acute stroke.

BACKGROUND: Although recanalization can be successful, microcirculatory dysfunction is common in acute large vessel occlusive stroke (LVOS). We assessed the microcirculation time by postprocessing software and analyzed its impact on prognosis in patients treated with mechanical thrombectomy (MT). METHODS: Patients with acute LVOS treated with MT were retrospectively enrolled consecutively. We measured the time to peak (TTP) and cerebral circulation time (CCT) in regions of interest on digital subtraction angiography using syngo iFlow software (Siemens Healthineers, Forchheim, Germany). A modified Rankin score ≤2 at 90 days was defined as a favorable outcome. Logistic regression was used to analyze the effect of each time parameter on prognosis. Then, we included time parameters in the baseline model to construct receiver operating characteristic (ROC) curves to assess the predictive ability for prognosis. RESULTS: A total of 215 patients were finally included. Of them, 118 (54.9%) had a favourable outcome at 90 days. Multivariate analysis showed that the microvascular cerebral circulation time (mCCT) was significantly associated with poor outcomes (odds ratio (OR) 2.061, 95% confidence interval (CI) 1.414 to 3.005 p<0.001). The area under the ROC curve was significantly enhanced by including mCCT in the baseline model (0.859 vs 0.829, p=0.016, DeLong test). CONCLUSIONS: The mCCT immediately after recanalization is a powerful predictive factor for 90-day functional prognosis.

Chemokine receptor 7 mediates miRNA-182 to regulate cerebral ischemia/reperfusion injury in rats.

AIMS: Chemokine receptor 7 (CXCR7) exerts protective effects on the brain. MicroRNAs (miRNAs) are involved in cerebral ischemia/reperfusion (I/R) injury, but their involvement in CXCR7-mediated brain protection is unknown. In this study, we investigated the role of miRNAs in CXCR7-mediated brain protection. METHODS: CXCR7 levels in peripheral blood samples from patients with acute ischemic stroke (AIS) and ischemic penumbra area brain tissues from middle cerebral artery occlusion (MCAO) rats after recanalization were measured. An miRNA microarray analysis was performed to examine the expression of miRNAs caused by CXCR7 knockdown in ischemic penumbra area brain tissue in middle cerebral artery occlusion-reperfusion rats and to predict corresponding downstream target genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed the most enriched pathways. A dual-luciferase reporter assay confirmed the direct regulation of miR-182 on the target gene TCF7L2. The correlation between TCF7L2 and CXCR7/miR-182 was verified using rescue assays. RESULTS: CXCR7 expression was upregulated in MCAO rats and mechanical thrombectomy patients with AIS compared to that in controls. The motor and sensory functions of MCAO rats with CXCR7 knockdown further decreased, and the infarct volume and cerebral edema increased. miRNA microarray data showed that seven miRNAs were differentially expressed after shRNA-CXCR7 treatment. The dual-luciferase reporter assay confirmed that miR-182 directly targeted the TCF7L2 gene. Rescue assays confirmed that TCF7L2 is downstream of CXCR7/miR-182. KEGG pathway analysis showed that the Hippo pathway may be a key pathway in CXCR7 upregulation and plays a role in protecting the brain after interventional surgery. Animal experiments have shown that CXCR7-mediated cerebral I/R injury promotes the phosphorylation of key molecules YAP and TAZ in the Hippo pathway. CONCLUSION: CXCR7 protects against cerebral I/R injury, possibly via the miR-182/TCF7L2/Hippo pathway. These results indicate that CXCR7 affects cerebral ischemia-reperfusion injury through miRNA regulation and downstream pathways.

First-pass effect in patients with acute vertebrobasilar artery occlusion undergoing thrombectomy: insights from the PERSIST registry.

Background: Achieving rapid and complete vascular recanalization in patients with acute large vessel occlusion can significantly improve patients' prognosis. Objective: We aimed to investigate the potential contribution of the first-pass effect (FPE) to the clinical outcome of patients with acute vertebrobasilar artery occlusion (VBAO). Methods: We retrospectively analyzed the data of patients who underwent endovascular thrombectomy (EVT) caused by VBAO in a multicentered retrospective registry dataset. FPE was defined as successful recanalization [modified thrombolysis in cerebral infarction (mTICI) 2b/3 as modified FPE (mFPE); mTICI 3 as true FPE (tFPE)] after one pass of the device without rescue therapy. The baseline characteristics and procedural and clinical outcomes were analyzed. Multivariate analysis was used to explore the predictors of FPE and the relationship between FPE and 90-day prognosis. Results: A total of 508 patients (age, 63.7 ± 13.1 years, male, 71.6%) were finally included, 29.9% (152/508) of whom achieved mFPE, and 21.1% (107/508) of whom achieved tFPE. FPE was significantly associated with improved clinical outcomes, regardless of mFPE [odds ratio (OR): 0.601, 95% confidence interval (CI): 0.370-0.977, p = 0.040] and tFPE (OR: 0.547, 95% CI: 0.318-0.940, p = 0.029). The use of contact aspiration, favorable collateral status, cardioembolic etiology, and basilar artery occlusion were statistically significant predictors of mFPE and tFPE, whereas hypertension was a negative predictor. Intravenous (IV) recombinant tissue plasminogen activator (rt-PA) prior to EVT was a positive predictor of mFPE but not of tFPE. Conclusion: FPE was associated with significantly favorable outcomes in EVT patients with VBAO. The predictors of FPE include infarct etiology, the site of occlusion, collateral status, EVT strategies, and IV rt-PA bridging strategies. Trial registration number: URL: http://www.chictr.org.cn/; Unique identifier: ChiCTR2000033211.

Post-ASPECTS based on hyperdensity in NCCT immediately after thrombectomy is an ultra-early predictor of hemorrhagic transformation and prognosis.

Background and Purpose: Almost half of the patients exhibit futile recanalization after thrombectomy; however, the early postoperative predictors of futile recanalization remain unclear. We analyzed the relationship of post-thrombectomy ASPECTS (Post-ASPECTS) with 90-day prognosis and hemorrhagic transformation (HT). Methods: We collected data from patients with acute ischemic stroke (AIS) with anterior-circulation large vessel occlusion (ACLVO) who were treated via thrombectomy within 10 h in 3 hospitals. Successful endovascular recanalization was achieved (modified thrombolysis in cerebral ischemia [mTICI] 2b/3). Non-contrast computed tomography (NCCT) examination was performed immediately (within 1 h) after thrombectomy. Post-ASPECTS were scored based on the brain parenchymal hyperdensity in NCCT according to the ASPECTS scoring method. HT was defined according to the ECASS II classification criteria. Linear correlation, logistic regression, and receiver operating characteristic curve analyses were used to determine the influencing factors and best predictive value of 90-day prognosis, 90-day death, and HT. Results: A total of 231 patients were enrolled. The good prognosis rate, mortality rate, and HT rate were 57.1, 9.5, and 38.3%, respectively. The Post-ASPECTS affected poor prognosis, death, and HT. The best predictive value of Post-ASPECTS for poor prognosis, death, and HT was 7. The specificities of Post-ASPECTS for predicting HT, poor prognosis, and death were 87.6% (AUC, 0.811; P < 0.001), 87.1% (AUC, 0.768; P < 0.001), and 73.7% (AUC, 0.748; P < 0.001), with positive predictive values of 74.2, 75.7, and 21.4%, respectively. Conclusion: Post-ASPECTS predicted 90-day prognosis, death, and HT with high specificity and high positive predictive value in patients with AIS with ACLVO. Post-ASPECTS may be an ultra-early predictor of prognosis after thrombectomy.

Prognosis of Ischemic Stroke Patients Undergoing Endovascular Thrombectomy is Influenced by Systemic Inflammatory Index Through Malignant Brain Edema.

Purpose: The systemic immune inflammatory index (SII), as a new marker, is widely used to predict the disease prognosis. We investigated the predictive value of SII for malignant cerebral edema (MCE) and whether postoperative MCE mediates the relationship between SII and functional prognosis in patients undergoing endovascular thrombectomy (EVT). Patients and Methods: A total of 829 patients with anterior circulation large-vessel occlusive stroke (LVOS) were registered, and 675 (81.4%) met the inclusion criteria. We collected baseline data upon admission, including SII. Postoperative computed tomography was performed to assess the presence and grading of cerebral edema (CED), and MCE was defined as a CED score of 3. A good prognosis was defined as a modified Rankin Scale (mRS) score of 0-2 at the 90-day follow-up. Results: A total of 132 patients developed MCE after EVT. The patients were divided into MCE and non-MCE groups, and univariate and multifactorial analyses were performed. Among these risk factors, an elevated SII was independently correlated with the occurrence of MCE. In addition, the receiver operating characteristic (ROC) curve was used to assess the predictive capability of SII levels for prognosis. The area under the ROC was 0.69, and the optimal critical value was 2.14. In addition, postoperative MCE may partially account for the poorer functional prognosis of patients with elevated SII (regression coefficient changed by 40.3%). Conclusion: The SII is an independent predictor of malignant brain edema after EVT. Postoperative MCE is partly the reason for the poorer prognosis in patients with elevated SII.

Pre-Existing Non-Disabling Encephalomalacia Confers Risk to Stroke Outcomes After Endovascular Treatment.

BACKGROUND: Patients with previous stroke episodes tend to have poor outcomes after an endovascular treatment (EVT). Encephalomalacia (EM) is an objective indicator of previous strokes but has not been systematically investigated. The fundamental aim of this exploration is to investigate the effects of a pre-existing non-disabling EM on clinical outcomes after EVT. METHODS: Consecutive patients undergoing an EVT due to the anterior circulation large vessel occlusion (LVO) strokes were enrolled in the study. The pre-existing EM was defined as the focal hypodense lesions (≥ 3 mm in maximum diameter) on a non-contrast cranial CT using axial images before EVT. The primary outcome was the 90-day functional assessment using the modified Rankin Scale (mRS) score. The safety outcome was the incidence of symptomatic intracranial hemorrhage (sICH) defined as any hemorrhage within 24 h after an EVT, which is responsible for an increase of ≥ 4 points in the score of National Institutes of Health Stroke Scale (NIHSS). RESULTS: Of the 433 patients analyzed in this investigation, a pre-existing non-disabling EM was observed in 106 (24.5%) patients. After adjusting for potential confounding factors, patients with contralateral EM (OR = 2.68, 95% CI = 1.13-6.31; P = 0.025) and with an EM+ > 20 mm in maximum diameter (OR = 2.21, 95% CI = 1.01-4.85; P =0.048) were substantially associated with unfavorable outcomes (mRS > 2). For the sICH, we did not observe any association with the pre-existing EM (P > 0.05). CONCLUSIONS: A pre-existing non-disabling EM is common and safe in patients undergoing EVT. However, a contralateral EM and the large size of EM may predict an unfavorable outcome at 90 days, which should receive more attention before EVT.

A Pre-Interventional Scale to Predict in situ Atherosclerotic Thrombosis in Acute Vertebrobasilar Artery Occlusion Patients.

Background and Purpose: Determining the occlusion mechanism before endovascular treatment (EVT) is of great significance for acute large vessel occlusion patients. We aimed to develop and validate a simple pre-EVT scale with readily available variables for predicting in situ atherosclerotic thrombosis (ISAT) in acute vertebrobasilar artery occlusion (VBAO) patients. Materials and Methods: Consecutive patients were retrieved from Nanjing Stroke Registry Program between January 2014 and December 2019 as a derivation cohort. Anonymous data of consecutive patients between January 2014 and December 2019 were collected from another comprehensive stroke center as an external validation cohort. Demographics, medical histories, and clinical characteristics were collected. ISAT was defined according to the following criteria: (a) detection of moderate to severe (≥50%) stenosis or stenosis with significant distal flow impairment at the occluded segment when successful reperfusion was achieved; (b) transient visualization of eccentric plaque contour or a recurrent re-occlusion tendency when reperfusion was unsuccessful. Logistic regression was taken to develop a predictive scale. The performance of the scale was assessed by area under the receiver operating characteristic curve (AUC) and Hosmer-Lemeshow test. Results: ISAT was observed in 41 of 95 (43.2%) patients included in the derivation cohort. The ISAT predictive scale consisted of three pre-interventional predictors, including the history of hypertension, atrial fibrillation rhythm, and baseline serum glucose level ≥7.55 mmol/L. The model depicted acceptable calibration (Hosmer-Lemeshow test, P = 0.554) and good discrimination (AUC, 0.853; 95% confidence interval, 0.775-0.930). The optimal cutoff value of the ISAT scale was 1 point with 95.1% sensitivity, 64.8% specificity, and 77.9% accuracy. In the validation cohort, the discrimination ability was still promising with an AUC value of 0.800 (0.682-0.918). Conclusion: The three-item scale comprised of the history of hypertension, atrial fibrillation rhythm, and dichotomous serum glucose level had a promising predictive value for ISAT before EVT in acute VBAO patients.