Changes of NLRP3 in serum and cerebrospinal fluid of patients after moderate to severe traumatic brain injury and their predictive values for prognosis.

BACKGROUND: Traumatic brain injury (TBI) remains a major concern for global health. Recent studies have suggested the role of NOD-like receptor pyrin domain-containing protein 3 (NLRP3), an inflammatory marker, in the cerebrospinal fluid (CSF) and serum as potential indicators of TBI prognosis. The objective of the study was to characterize NLRP3 as a clinically applicable tool for predicting the outcomes of TBI patients. METHODS: A total of 270 patients with moderate to severe TBI were included in this retrospective analysis. Serum and CSF samples were collected at 1-, 3-, 7-, and 21-day post-injury to measure NLRP3 levels. The prognosis of patients was evaluated after 3 months using the Glasgow Outcome Scale (GOS). Patients were categorized into good prognosis (GOS score >3) and poor prognosis (GOS score ≤3) groups. The relationship between NLRP3 levels and prognosis was analyzed. RESULTS: Patients with poor prognosis had significantly elevated NLRP3 levels in their serum on days 1 and 3 post-injury compared with those with a good prognosis. The difference was more pronounced during these early days compared with days 7 and 21. However, NLRP3 levels in CSF consistently showed a large difference between the two groups throughout the observation period. Receiver operating characteristic analysis revealed that the level of NLRP3 in the CSF on day 3 post-injury had the highest predictive value for prognosis, with an area under the curve of 0.83, followed by the level of NLRP3 in the serum on day 3 post-injury. CONCLUSIONS: The levels of NLRP3, especially in the CSF on day 3 post-injury, can serve as a potential biomarker for predicting prognosis in moderate to severe TBI patients. Early measurement of NLRP3 levels can provide valuable insights into patient outcomes and guide therapeutic strategies.

Activating PKA signaling increases exosome production and attenuates cerebral ischemia-reperfusion injury by regulating Cx43 expression.

BACKGROUND: Connexin 43 (Cx43) plays a crucial role in mediating intracellular communication and facitating the interaction between exosomes and recipient cells. This study investigates whether the activation of cAMP/protein kinase A (PKA) can regulate exosomal Cx43 expression and contribute to the functional recovery following ischemia-reperfusion (I/R) injury. METHODS: An intraluminal vascular occlusion was performed on Lewis rats to simulate I/R injury. Concurrently, a PKA activator (8-Bromo-cAMP, 5 mg kg-1) or PKA inhibitor (H 89 2HCl, 20 mg kg-1) was administered intravenously via the tail vein (n = 10). Exosomes were isolated from cerebrospinal fluid, and the expression of exosomal markers (CD63 and CD81) and Cx43 was analyzed using Western blot. The expression of CD63 and CD81 in astrocytes was measured to assess exosome uptake. Spatial learning and memory capability were evaluated using the Morris water maze test. RESULTS: 8-Bromo-cAMP significantly increased exosome release in cerebrospinal fluid, accompanied by elevated Cx43 expression. Additionally, 8-Bromo-cAMP enhanced exosome uptake by astrocytes, alleviated blood-brain barrier damage and edema, and improved cognitive function. CONCLSIONS: PKA activation enhances exosome production, promotes cognitive function recovery, and attenuates cerebral I/R injury by up-regulating exosomal Cx43 expression.

Research on the mechanism of TWSG1 in the malignant progression of glioma cells and tumor-associated macrophage infiltration.

Gliomas are malignant tumors of the central nervous system; current treatment methods have low efficacy. Twisted gastrulation BMP signaling modulator 1 (TWSG1) has been shown to play a role in gliomas but it is not known whether TWSG1 participates in glioma pathogenesis and macrophage immune regulation. This study identified a total of 24 differentially expressed genes with survival differences in gliomas using bioinformatics analysis. Among them, TWSG1 exhibited the strongest correlation with gliomas and was positively correlated with macrophage enrichment. The results showed that TWSG1 was highly expressed in various glioma cell lines, with the highest expression observed in the A172 cell line. Silencing TWSG1 significantly decreased the viability, migration, and invasion of A172 cells in vitro and tumor growth in a mouse xenograft model in vivo. It also reduced the expression of the matrix metalloproteinases MMP2 and MMP9 both in vivo and in vitro. Silencing TWSG1 significantly reduced the expression of M2 macrophage makers and upregulated the expression of M1 macrophage markers in A172 cells and tumor tissues. These data suggest that interference with TWSG1 suppressed the progression of A172 glioma cells and regulated immune infiltration.

Association of serum uric acid level with intracranial aneurysms: A Mendelian randomization study.

Objective: Numerous studies have posited the involvement of serum uric acid (SUA) in the pathogenesis and progression of various cardiovascular diseases, particularly aortic aneurysms. However, the casual effect of SUA level on intracranial aneurysms (IAs) was rarely studied. Consequently, we aimed to explore the causal association between SUA and IAs using Mendelian randomization (MR) analysis. Methods: We conducted a two-sample MR analysis with SUA as the exposure variable and IAs as the outcome variable. Genome-wide association study (GWAS) datasets for SUA were acquired from the Open GWAS catalog, including 389,404 European and 129,405 East Asian individuals. The dataset for IAs was sourced from a meta-analysis of GWASs comprising 317,636 individuals across different ancestral populations (European: 7495 cases and 71,934 controls; East Asian: 3259 cases and 234,948 controls). The MR analyses were performed according to populations (European and East Asian) and IAs status [unruptured IAs (uIAs) or aneurysmal subarachnoid hemorrhage (aSAH)], respectively. The inverse variance weighted (IVW) method was employed as primary analysis to discern causal estimates. Results: Our findings revealed that an elevated genetically predicted SUA level (mg/dL) correlated with an increased risk of IAs among the European population (OR = 1.29 [95%CI:1.05-1.57], P = 0.013) and East Asian population (OR = 1.56 [95%CI: 1.27-1.92], P < 0.001). Among European individuals, subgroup analysis indicated a persistent causal association of SUA with uIAs (OR = 1.50 [95%CI: 1.08-2.08], P = 0.015) and aSAH (OR = 1.26 [95%CI: 1.00-1.60], P = 0.049). However, subgroup analysis in East Asian populations was not conducted due to the lack of separate data on uIAs and aSAH. Conclusions: Our MR analysis demonstrated a causal relationship between elevated SUA levels and an amplified risk of IAs. Further rigorous investigations are imperative to provide evidence and elucidate the underlying mechanisms.

Machine learning models reveal the critical role of nighttime systolic blood pressure in predicting functional outcome for acute ischemic stroke after endovascular thrombectomy.

Background: Blood pressure (BP) is a key factor for the clinical outcomes of acute ischemic stroke (AIS) receiving endovascular thrombectomy (EVT). However, the effect of the circadian pattern of BP on functional outcome is unclear. Methods: This multicenter, retrospective, observational study was conducted from 2016 to 2023 at three hospitals in China (ChiCTR2300077202). A total of 407 patients who underwent endovascular thrombectomy (EVT) and continuous 24-h BP monitoring were included. Two hundred forty-one cases from Beijing Hospital were allocated to the development group, while 166 cases from Peking University Shenzhen Hospital and Hainan General Hospital were used for external validation. Postoperative systolic BP (SBP) included daytime SBP, nighttime SBP, and 24-h average SBP. Least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), Boruta were used to screen for potential features associated with functional dependence defined as 3-month modified Rankin scale (mRS) score ≥ 3. Nine algorithms were applied for model construction and evaluated using area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy. Results: Three hundred twenty-eight of 407 (80.6%) patients achieved successful recanalization and 182 patients (44.7%) were functional independent. NIHSS at onset, modified cerebral infarction thrombolysis grade, atrial fibrillation, coronary atherosclerotic heart disease, hypertension were identified as prognostic factors by the intersection of three algorithms to construct the baseline model. Compared to daytime SBP and 24-h SBP models, the AUC of baseline + nighttime SBP showed the highest AUC in all algorithms. The XGboost model performed the best among all the algorithms. ROC results showed an AUC of 0.841 in the development set and an AUC of 0.752 in the validation set for the baseline plus nighttime SBP model, with a brier score of 0.198. Conclusion: This study firstly explored the association between circadian BP patterns with functional outcome for AIS. Nighttime SBP may provide more clinical information regarding the prognosis of patients with AIS after EVT.

Neonatal microglia transplantation at early stage but not late stage after traumatic brain injury shows protective effects in mice.

The transplantation of neonatal microglia suppresses neuroinflammation caused by traumatic brain injury (TBI). This research aimed to explore the optimal time point of neonatal microglia transplantation for the best effect on the improvement of long-term cognitive function and inflammatory response in mouse models. qPCR and immunoblotting showed that the level of Iba1 gradually increased to the highest on day 7 and then gradually declined in TBI mice. Furthermore, it was observed that the level of CD86 and TNF-α increased to the highest after 7 days and subsequently was maintained until day 21, whereas the level of CD206 and IL-10 increased to the highest after 24 h and subsequently decreased until day 21 by qPCR and enzyme-linked immunosorbent assay. Afterward, it was shown that the neonatal microglia transplantation within 1 h significantly attenuated anxiety-like behavior and improved cognitive impairments in TBI mice. Mechanism exploration showed that the neonatal microglia could significantly decrease the level of cleaved caspase-3, M1/M2 polarization, and inflammatory cytokine (TNF-α) while increasing the level of anti-inflammatory factor IL-10 in TBI mice after transplantation within 1 h. Here, our findings demonstrated that neonatal microglia transplantation within 1 h significantly attenuated anxiety-like behavior and cognitive impairments caused by TBI.NEW & NOTEWORTHY The study demonstrated that neonatal microglia transplantation within 1 h significantly inhibited the pathogenesis of traumatic brain injury (TBI) in mouse models through inhibition of M1 polarization and promotion of M2 polarization.

The Predictive Value of Cerebral Veins on Hemorrhagic Transformation After Endovascular Treatment in Acute Ischemic Stroke Patients: Enhanced Insights From Venous Collateral Circulation Analysis Using Four-Dimensional CTA.

RATIONALE AND OBJECTIVES: A significant complication of endovascular treatment (EVT) is hemorrhagic transformation (HT), which can worsen the outcomes of patients with acute ischemic stroke (AIS). This study aimed to evaluate the predictive value of venous collateral circulation on HT in patients with AIS undergoing EVT. MATERIALS AND METHODS: We retrospectively analyzed 126 patients with AIS who received EVT. The four-dimensional computed tomography angiography-based venous collateral score (4D-VCS) and arterial collateral circulation score (4D-ACS) were used to assess venous and arterial collaterals, respectively. Significant variables were identified using the least absolute shrinkage and selection operator algorithm. Logistic regression analysis, receiver operating characteristic (ROC) analysis, and DeLong's test were conducted. RESULTS: HT occurred in 41.3% (52/126) of patients. Higher clot burden score (CBS; odds ratio [OR]: 0.82, 95% confidence interval [CI]: 0.71-0.95, p = 0.009), better arterial collateral circulation (OR: 0.59, 95% CI: 0.42-0.83, p = 0.003), and better venous collateral circulation (OR: 0.85, 95% CI: 0.73-0.97, p = 0.020) were significantly associated with reduced HT risk. The area under the curve (AUC) values for CBS, 4D-ACS, and 4D-VCS were 0.730, 0.772, and 0.795, respectively. Model 1 (4D-VCS+CBS) achieved AUC of 0.820, significantly improving over CBS alone (p = 0.0133). Model 2 (4D-VCS+4D-ACS) had an AUC of 0.829, significantly higher than 4D-ACS alone (p = 0.0271). Model 3 (4D-ACS+CBS) had an AUC of 0.790. Model 4 (4D-VCS+4D-ACS+CBS) showed highest AUC of 0.851. Significant correlations were found between 4D-VCS and ischemic core volume (r = -0.684, p < 0.001) and between 4D-VCS and mismatch ratio (r = 0.558, p < 0.001). CONCLUSION: Evaluating venous collateral circulation using 4D-VCS could improve HT risk prediction in patients with AIS after EVT. When combined with other predictors, 4D-VCS may potentially enhance diagnostic performance, which suggests the potential role of venous collateral circulation in predicting HT risk.

Integrated analysis reveals the potential of cluster of differentiation 86 as a key biomarker in high-grade glioma.

This study aimed to evaluate the potential of cluster of differentiation 86 (CD86) as a biomarker in high-grade glioma (HGG). The TCGA and TCIA databases were used to obtain the CD86 expression value, clinical data, and MRI images of HGG patients. Prognostic values were assessed by the Kaplan-Meier method, Receiver operating characteristic curve (ROC), Cox regression, logistic regression, and nomogram analyses. CD86-associated pathways were also explored. We found that CD86 was significantly upregulated in HGG compared with the normal group. Survival analysis showed a significant association between CD86 high expression and shorter overall survival time. Its independent prognostic value was also confirmed. These results suggested the possibility of CD86 as a biomarker in HGG. We also innovatively established 2 radiomics models with Support Vector Machine (SVM) and Logistic regression (LR) algorithms to predict the CD86 expression. The 2 models containing 5 optimal features by SVM and LR methods showed similar favorable performance in predicting CD86 expression in the training set, and their performance were also confirmed in validation set. These results indicated the successful construction of a radiomics model for non-invasively predicting biomarker in HGG. Finally, pathway analysis indicated that CD86 might be involved in the natural killer cell-mediated cytotoxicity in HGG progression.

Network meta-analysis of first-line thrombectomy strategy for acute posterior circulation strokes: a preliminary evaluation for combined approach.

Objective: Thrombectomy may provide superior results compared to best medical care for acute posterior circulation strokes (PCS). Contact aspiration (CA), stent retriever (SR), and combined SR + CA (SRA) are commonly employed as first-line techniques. However, the optimal strategy and the role of SRA remain uncertain. Methods: Systematic searching was conducted in three databases (PubMed, Embase, and Cochrane). Network meta-analyzes were performed using random-effects models. The reperfusion and clinical outcomes were compared. Pooled outcomes were presented as odds ratios (OR) with 95% confidence intervals (CI). Rankograms with surface under the cumulative ranking curve (SUCRA) were calculated. Results: Seventeen studies were included, involving a total of 645 patients who received first-line CA, 850 patients who received SR, and 166 patients who received SRA. Regarding final recanalization outcomes, both first-line SRA (OR = 3.2, 95%CI 1.4-11.0) and CA (OR = 2.1, 95%CI 1.3-3.7) demonstrated superiority over SR in achieving successful reperfusion [modified Thrombolysis In Cerebral Infarction (mTICI) 2b-3], with values of SUCRA 91.1, 58.5, and 0.4%, respectively. In addition, first-line SRA showed an advantage in achieving final mTICI 2c/3 compared to CA (OR = 3.6, 95%CI 0.99-16.0) and SR (OR = 6.4, 95%CI 1.3-35.0), with SUCRA value of 98.0, 44.7, and 7.2%, respectively. Regarding reperfusion outcome after the first pass, SRA also achieved a higher rate of mTICI 3 than SR (OR = 4.1, 95%CI 1.3-14.0), while CA did not (SUCRA 97.4, 4.6, 48.0%). In terms of safety outcomes, first-line CA was associated with a lower incidence of symptomatic intracranial hemorrhage (sICH) compared to SR (OR = 0.38, 95%CI 0.1-1.0), whereas the SRA technique did not (SUCRA 15.6, 78.6, 55.9%). Regarding clinical prognosis, first-line CA achieved a higher proportion of functional independence (modified Rankin Scale (mRS) 0-2) at 90 days than SR (OR = 1.4, 95%CI 1.1-1.9), whereas SRA did not (SUCRA 90.5, 17.4, 42.1%). Conclusion: For acute PCS, a first-line CA strategy yielded better results in terms of final successful reperfusion and 90-day functional independence compared to SR. As the combined technique, first-line SRA was associated with superior first-pass and final reperfusion outcomes compared to SR. However, no significant difference was observed in functional independence achieved by first-line SRA compared to the other two strategies. Further high-quality studies are warranted.

Serum Sestrin2 Emerges as a Prognostic Biomarker of Human Aneurysmal Subarachnoid Hemorrhage: A Prospective Observational Cohort Single-Center Study.

Background: Sestrin2 functions as a neuroprotective factor. Herein, serum sestrin2 was investigated with respect to its associations with severity, delayed cerebral ischemia (DCI) and prognosis of aneurysmal subarachnoid hemorrhage (aSAH). Methods: In this prospective, observational, cohort, single-center study, serum sestrin2 levels were measured at entry into the study in 45 healthy controls and at admission in 135 aSAH patients. Also, they were gauged in other time points (namely, at days 1, 2, 3, 5 and 7) among 45 patients. Unfavorable prognosis was defined as extended Glasgow Outcome Scale (GOSE) scores of 1-4 at six months after aSAH. Results: Serum sestrin2 levels were immediately raised at admission in patients, increased thereafter, peaked at day 2, declined afterwards till day 7, and were significantly higher than those in controls (all P<0.001). Serum sestrin2 levels had independent correlation with Hunt-Hess scores (beta, 1.715; 95% confidence interval (CI), 0.595-2.835; P=0.003) and modified Fisher scores (beta, 2.505; 95% CI, 1.102-3.907; P=0.001). Alternatively, serum sestrin2 levels, which were independently correlated with 6-month GOSE scores (beta, -0.050; 95% CI, -0.099-0.001; P=0.044), were independently associated with DCI (odds ratio, 1.079; 95% CI, 1.008-1.156; P=0.029) and unfavorable prognosis (odds ratio, 1.093; 95% CI, 1.020-1.172; P=0.012). DCI and prognosis prediction models, which were composed of serum sestrin2, Hunt-Hess scores and modified Fisher scores, were comparatively stable and clinically beneficial under calibration curve and decision curve. Prognosis prediction model showed significantly higher area under receiver operating characteristic curve than serum sestrin2, Hunt-Hess scores and modified Fisher scores alone (all P<0.05). Conclusion: A significant enhancement of serum sestrin2 levels after aSAH is independently related to severity, DCI and poor prognosis following aSAH. The models incorporating serum sestrin2 perform well in predicting the DCI and prognosis of aSAH patients. Presumably, determination of serum sestrin2 may be of clinical significance in aSAH.

First-line contact aspiration versus first-line stent retriever for acute ischemic stroke with M2 occlusion: A systematic review and meta-analysis.

OBJECTIVE: Mechanical thrombectomy is widely used for acute ischemic stroke caused by middle cerebral artery M2 segment occlusion. However, the comparison between contact aspiration (CA) and stent retriever (SR) used as first-line techniques for acute M2 occlusion is still unclear. We aimed to perform a systematic review and meta-analysis on this issue. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement was followed. Three databases (Pubmed, Embase, and Cochrane) were searched. The Newcastle-Ottawa scale was used to assess the risk of bias for the included studies. We focused on two main outcomes, the final successful reperfusion (modified Thrombolysis in Cerebral Infarction mTICI 2b/3) and 90-day functional independence (modified Rankin Scale score 0-2). The meta-analyses were performed using the random-effects models. RESULTS: Seven observational studies were included for systematic review. Only one study indicated a superiority of first-line SR in achieving final successful reperfusion, while the other six studies did not show significant difference between these two techniques. And all the seven studies showed comparable proportion of 90-day functional independence. Five studies were available for meta-analysis with 601 patients (239 received first-line CA, 362 received first-line SR). The pooled results also suggested that the proportion of final successful reperfusion (OR=1.18, 95%CI 0.72-1.93, I2 =0%) and 90-day functional independence (OR=1.18, 95%CI 0.82-1.68, I2 =0%) were comparable between these two strategies. CONCLUSION: For patients with acute M2 occlusion, first-line CA and SR techniques could achieve similar final reperfusion outcomes and 90-day clinical prognosis. Further studies with randomized controlled design are needed.

First-line contact aspiration versus first-line stent retriever for acute posterior circulation strokes: an updated meta-analysis.

BACKGROUND: Both stent retriever (SR) and contact aspiration (CA) are widely used as first-line strategies for acute posterior circulation strokes (PCS). However, it is still unclear how CA and SR compare as the first-line treatment of acute PCS. Several new studies have been published recently, so we aimed to perform an updated meta-analysis. METHODS: The meta-analysis was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement. Random-effects models were performed to pool the outcomes and the value of I2 was calculated to assess the heterogeneity. RESULTS: Ten observational studies with 1189 patients were included, among whom 492 received first-line CA and 697 received first-line SR. The pooled results revealed that first-line CA could achieve a significantly higher proportion of modified Thrombolysis In Cerebral Infarction (mTICI) 2b/3 (OR 1.90, 95% CI 1.33 to 2.71, I2=0%), mTICI 3 (OR 1.95, 95% CI 1.15 to 3.31, I2=59.6%), first-pass effect (OR 2.91, 95% CI 1.51 to 5.58, I2=0%), lower incidence of new-territory embolic events (OR 0.20, 95% CI 0.05 to 0.83, I2=0%), and shorter procedure time (mean difference -29.4 min, 95% CI -46.8 to -12.0 min, I2=62.8%) compared with first-line SR. At 90-day follow-up, patients subjected to first-line CA showed a higher functional independence (modified Rankin Scale score 0-2; OR 1.38, 95% CI 1.01 to 1.87, I2=23.5%) and a lower mortality (OR 0.71, 95% CI 0.50 to 1.00, p=0.050, I2=0%) than those subjected to first-line SR. CONCLUSIONS: This meta-analysis suggests that the first-line CA strategy could achieve better recanalization and clinical outcomes for acute PCS than first-line SR. Limited by the quality of included studies, this conclusion should be drawn with caution.

Histological composition behind CT-based thrombus density and perviousness in acute ischemic stroke.

BACKGROUND: Clot composition could impact recanalization outcomes of thrombectomy, and preoperative imaging markers may help know about the histological components of thrombus. METHODS: Consecutive patients who underwent thrombectomy from June 2017 to December 2019 were reviewed. The mean Hounsfield unit (HU) of thrombus (aHU) and contralateral artery (cHU) were recorded based on non-enhanced CT. The relative thrombus density was calculated (dHU=aHU-cHU). Hyperdense artery sign (HAS) was identified if dHU≥ 4HU. The clot perviousness was evaluated via thrombus attenuation increase (δHU) on contrast-enhanced CT compared to non-enhanced CT. Pervious clots were identified when δHU≥ 11HU. Tissue quantification for thrombus was based on Martius Scarlet Blue staining, using the Orbit Imaging Analysis Software. Spearman rank correlations was used to detect the association between imaging markers and clot composition. The differences in clinical characteristics were compared according to the presence of HAS or pervious clots. RESULTS: Fifty-three patients were included. The dHU was positively correlated with erythrocyte fractions (r = 0.337, p = 0.014), while there was no significant association between aHU and erythrocyte components (r = 0.146, p = 0.296). HAS (+) patients showed a comparable proportion of modified Thrombolysis In Cerebral Infarction (mTICI) 2b-3 (94.6% vs. 87.5%, p = 0.740) and modified Rankin Scale score (mRS) 0-2 (35.1% vs. 56.3%, p = 0.152) compared with those HAS (-). Forty-seven cases were available for the analysis of clot perviousness. Clot perviousness was negatively associated with platelet fractions (r = -0.577, p < 0.001). Patients with pervious clots also showed a comparable proportion of mTICI 2b-3 (86.2% vs. 100%, p = 0.283) and mRS 0-2 (37.9% vs. 50.0%, p = 0.416) compared with impervious clots. CONCLUSIONS: This study suggests that relative thrombus density was positively correlated with erythrocyte fractions, while clot perviousness showed a negative relationship with platelet components. Yet, the presence of HAS or pervious clots did not show significant associations with recanalization and clinical outcomes. The conclusions should be drawn with caution.

Preliminary Application of a Quantitative Collateral Assessment Method in Acute Ischemic Stroke Patients With Endovascular Treatments: A Single-Center Study.

Objectives: To develop an efficient and quantitative assessment of collateral circulation on time maximum intensity projection CT angiography (tMIP CTA) in patients with acute ischemic stroke (AIS). Methods: Eighty-one AIS patients who underwent one-stop CTA-CT perfusion (CTP) from February 2016 to October 2020 were retrospectively reviewed. Single-phase CTA (sCTA) and tMIP CTA were developed from CTP data. Ischemic core (IC) volume, ischemic penumbra volume, and mismatch ratio were calculated. The Tan scale was used for the qualitative evaluation of collateral based on sCTA and tMIP CTA. Quantitative collateral circulation (CCq) parameters were calculated semi-automatically with software by the ratio of the vascular volume (V) on both hemispheres, including tMIP CTA VCCq and sCTA VCCq. Spearman correlation analysis was used to analyze the correlation of collateral-related parameters with final infarct volume (FIV). ROC and multivariable regression analysis were calculated to compare the significance of the above parameters in clinical outcome evaluation. The analysis time of the observers was also compared. Results: tMIP CTA VCCq (r = 0.61, p < 0.01), IC volume (r = 0.66, p < 0.01), Tan score on tMIP CTA (r = 0.52, p < 0.01) and mismatch ratio (r = 0.60, p < 0.01) showed moderate negative correlations with FIV. tMIP CTA VCCq showed the best prognostic value for clinical outcome (AUC = 0.93, p < 0.001), and was an independent predictive factor of clinical outcome (OR = 0.14, p = 0.009). There was no difference in analysis time of tMIP CTA VCCq among observers (p = 0.079). Conclusion: The quantitative evaluation of collateral circulation on tMIP CTA is associated with clinical outcomes in AIS patients with endovascular treatments.

Identification of Predictors for Hemorrhagic Transformation in Patients with Acute Ischemic Stroke After Endovascular Therapy Using the Decision Tree Model.

PURPOSE: This study aimed to identify independent predictors for the risk of hemorrhagic transformation (HT) in arterial ischemic stroke (AIS) patients. METHODS: Consecutive patients with AIS due to large artery occlusion in the anterior circulation treated with mechanical thrombectomy (MT) were enrolled in a tertiary stroke center. Demographic and medical history data, admission lab results, and Circle of Willis (CoW) variations were collected from all patients. RESULTS: Altogether, 90 patients were included in this study; among them, 34 (37.8%) had HT after MT. The final pruned decision tree (DT) model consisted of collateral score and platelet to lymphocyte ratios (PLR) as predictors. Confusion matrix analysis showed that 82.2% (74/90) were correctly classified by the model (sensitivity, 79.4%; specificity, 83.9%). The area under the ROC curve (AUC) was 81.7%. The DT model demonstrated that participants with collateral scores of 2-4 had a 75.0% probability of HT. For participants with collateral scores of 0-1, if PLR at admission was <302, participants had a 13.0% probability of HT; otherwise, participants had an 75.0% probability of HT. The final adjusted multivariate logistic regression analysis indicated that collateral score 0-1 (OR, 10.186; 95% CI, 3.029-34.248; p < 0.001), PLR (OR, 1.005; 95% CI, 1.001-1.010; p = 0.040), and NIHSS at admission (OR, 1.106; 95% CI, 1.014-1.205; p = 0.022) could be used to predict HT. The AUC for the model was 0.855, with 83.3% (75/90) were correctly classified (sensitivity, 79.4%; specificity, 87.3%). Less patients with HT achieved independent outcomes (mRS, 0-2) in 90 days (20.6% vs. 64.3%, p < 0.001). Rate of poor outcomes (mRS, 4-6) was significantly higher in patients with HT (73.5% vs. 19.6%; p < 0.001). CONCLUSION: Both the DT model and multivariate logistic regression model confirmed that the lower collateral status and the higher PLR were significantly associated with an increased risk for HT in AIS patients after MT. PLR may be one of the cost-effective and practical predictors for HT. Further prospective multicenter studies are needed to validate our findings.

Risk of secondary embolism events during mechanical thrombectomy for acute ischemic stroke: A single-center study based on histological analysis.

OBJECTIVE: Secondary embolism (SE) is a common adverse event during mechanical thrombectomy (MT) for acute intracranial large vessel occlusion, which could lead to incomplete revascularization and increased maneuvers. However, the mechanisms behind SE are still unclear. In this study, we aimed to investigate the risk factors of SE, with a focus on clot composition. PATIENTS AND METHODS: Consecutive patients with retrieved clots were reviewed. Histologic examination for thrombus included Hematoxylin and eosin, Martius Scarlet Blue, immunohistochemistry for von Willebrand factor (VWF). Patients included were assigned to SE or no SE group. The differences in histological composition and clinical characteristics were compared, and logistic regression was conducted for predictors of SE. RESULTS: Fifty-four patients were included, of which 19 were identified as having an SE. For patients with SE, there was more history of stroke or transient cerebral ischemia (TIA) (57.9 % vs. 28.6 %, p = 0.035), more occlusion located in terminal internal carotid artery (ICA) (63.2 % vs. 25.7 %, p = 0.007), relatively more contact aspiration used as frontline strategy (68.4 % vs. 45.7 %, p = 0.110), and less eTICI2c-3 recanalization achieved (52.6 % vs. 91.4 %, p = 0.003). As for histologic composition, the clots in SE group showed a higher proportion of erythrocyte fractions (42.9 % vs. 26.8 %, p = 0.045), while the other components were comparable with the non-SE group. Multivariate analysis suggested that a history of stroke or TIA (OR 6.45, 95 %CI 1.41-29.44, p = 0.016) and ICA occlusion (OR 8.05, 95 %CI 1.80-36.10, p = 0.006) could independently predict SE. CONCLUSION: History of TIA or stroke and occlusion in the terminal ICA were found to be independent predictors for SE. Thrombus with a higher erythrocyte fractions might be more fragile. Further studies are needed.

Collateral Vessels on 4D CTA as a Predictor of Hemorrhage Transformation After Endovascular Treatments in Patients With Acute Ischemic Stroke: A Single-Center Study.

Objective: Although the benefits of good collateral circulation on infarct volume and outcomes have been confirmed in previous studies, few studies have investigated the relationship between hemorrhagic transformation (HT) and collateral circulation in acute ischemic stroke (AIS). This study aimed to assess whether collateral circulation is an essential factor of HT after endovascular treatments (EVTs). Methods: In total, 71 consecutive AIS patients who underwent EVTs between July 2015 and February 2019 were retrospectively studied. The correlations among HT, collateral vessels on 4D CT angiography (4D CTA), and other predictive factors for HT [e.g., National Institutes of Health Stroke Scale (NIHSS) score, age, sex, serum glucose, and atrial fibrillation history] were evaluated by logistic regression analysis. Results: The rate of hemorrhagic transformation was 42.3% (30/71) in AIS patients. Multivariate logistic regression showed that a good collateral status (OR 0.76, 95% CI 0.73-0.80) was associated with a lower risk of HT. History of atrial fibrillation (OR 2.35, 95% CI 1.96-2.82), baseline NIHSS scores (OR 2.00, 95% CI 1.72-2.32), and higher serum glucose levels (OR 1.70, 95% CI 1.57-1.85) were all independent risk factors of HT. Conclusions: Patients with poor collateral circulation are at a higher risk of HT after receiving endovascular therapy. Thus, variations in collateral circulation based on 4D CTA may be an important factor for personalized clinical treatments. In addition, high blood glucose, atrial fibrillation and the baseline NIHSS score are all important independent predictors of HT.

The role of diabetes mellitus on the thrombus composition in patients with acute ischemic stroke.

PURPOSE: Diabetes mellitus indicated poor clinical prognosis for patients with acute ischemic stroke. Furthermore, diabetes mellitus could also impact the hemostatic system, while its influence on the histological composition of thrombus is unclear. METHODS: Consecutive patients with retrieved clots were included. Histologic staining for thrombus included hematoxylin and eosin, Martius Scarlet Blue, immunohistochemistry for von Willebrand factor. The differences in clot composition were compared according to diabetes mellitus history or hyperglycemia (≥7.8 mmol/L) on admission. RESULTS: A total of 52 patients were included; half of them were diagnosed as diabetes mellitus previously. Diabetic patients showed higher serum glucose on admission (8.90 vs. 7.40, p = 0.012). The baseline characteristics (expect smoking history and thrombus location), procedural, and clinical outcomes were similar between diabetic patients and nondiabetic patients. As for histologic composition, thrombus in patients with diagnosed diabetes mellitus had more fibrin (44.2% vs. 28.3%, p = 0.004) and fewer red blood cells (26.0% vs. 42.9%, p = 0.013) and equivalent content of platelets (24.0% vs. 21.5%, p = 0.694) and von Willebrand factor (0.041 vs. 0.031, p = 0.234) than patients without diabetes mellitus. However, there was no statistical difference in the content of red blood cells (41.6% vs. 27.3%, p = 0.105), fibrin (37.6% vs. 34.3%, p = 0.627), platelets (21.2% vs. 24.2%, p = 0.498), and von Willebrand factor (0.038 vs. 0.034, p = 0.284) between patients with or without hyperglycemia on admission. CONCLUSION: Clots in diabetic patients had more fibrin and fewer erythrocyte components compared with patients without diabetes mellitus, while hyperglycemia on admission did not show association with clot composition. Further studies are needed to confirm these results.

Association Between Thrombus Density and Reperfusion Outcomes Using Different Thrombectomy Strategies: A Single-Center Study and Meta-Analysis.

Background: For patients with acute ischemic stroke (AIS), the thrombus density on non-enhanced CT (NECT) indicates the composition of the thrombus, a characteristic that impacts the efficacy of mechanical thrombectomy (MT). A previous meta-analysis suggested a correlation between higher thrombus density and successful reperfusion, but some new studies have drawn different conclusions. This single-center study and meta-analysis aimed to detect the association between thrombus density and reperfusion outcomes based on various thrombectomy strategies. Methods: We reviewed AIS patients who underwent MT at our center between July 2015 and May 2019. Thrombus density was recorded as mean Hounsfield Unit (HU) value on 1-mm reconstructed NECT, and expanded Thrombolysis In Cerebral Infarction (eTICI) scale was used to evaluate the reperfusion grade. The difference in thrombus density was examined according to reperfusion outcomes. Then, we systematically searched relevant literature on this issue. The random effect model was used to calculate standardized mean difference (SMD), and subgroup analysis was conducted according to MT strategies employed, including stent retriever (SR), contact aspiration (CA), Solumbra (a combination of SR and aspiration), and multiple thrombectomy modalities. Results: Sixty-four patients with anterior circulation AIS were included in our single-center study with 57 (89.1%) achieving successful reperfusion (eTICI2b-3). Retrospective analysis showed no significant difference in thrombus density between eTICI2b-3 and eTICI0-2a reperfusion (65.27 vs. 62.19, p = 0.462). As for systematic review, 11 studies were included in qualitative analysis, among which 6 had data available for meta-analysis. Pooled result showed that a comparable thrombus density between eTICI2b-3 and eTICI0-2a reperfusion (SMD 0.14, 95%CI -0.28 to 0.57, p = 0.50). Interestingly, in the SR subgroup, eTICI2b-3 reperfusion showed a significant higher thrombus density (SMD 0.53, 95%CI 0.10 to 0.96, p = 0.02), while an inverse trend was observed in the CA subgroup (SMD -0.48, 95%CI -0.88 to -0.07, p = 0.02). Conclusions: Although the pooled result of meta-analysis did not show a significant association between thrombus density and successful reperfusion, subgroup analysis implicated that the SR technique might be prone to retrieve high-density thrombus, while the CA subgroup showed an opposite tendency. Further studies are needed to confirm these results and to investigate its role in the optimization of thrombectomy strategy.

CT-based Higher Thrombus Density is associated with Secondary Embolism during Mechanical Thrombectomy: A Preliminary Observation.

BACKGROUND: Secondary embolism (SE) during mechanical thrombectomy (MT) for acute ischemic stroke (AIS) is the main reason for incomplete recanalization, while its risk factors are largely unknown. This study addresses a potential relationship between thrombus density on preinterventional computed tomography (CT) and the occurrence of SE. METHODS: We reviewed anterior circulation AIS patients who underwent MT from July 2015 to January 2019 in our center. Thrombus density was measured in Hounsfield Units (HU) on 1-mm and 5-mm preinterventional nonenhanced CT (NECT). Thrombus density, baseline characteristics, procedural, and clinical outcomes were compared between patients with SE and those without SE. Logistic regression was conducted to identified potential risk factors of SE. RESULTS: Sixty-four consecutively patients were included, of whom SE was identified in 16 (25.0%) patients. Compared with those without SE, patients with SE showed a higher thrombus density on both 1-mm (72.85 versus 64.28, P = .005) and 5-mm NECT (60.31 versus 49.71, P < .001), a higher proportion of atrial fibrillation (75.0% versus 45.8%, P = .043), a lower clot burden score (.5 versus 6.0, P = .029), and a higher proportion of front-line contact aspiration strategy (50.0% versus 16.7%, P = .020). Multivariate regression analysis showed that only thrombus density was the independent predictor of SE (for the model including HU values on 1-mm NECT, OR 1.11, 95%CI 1.01-1.23, P = .029; for the model including HU values on 5-mm NECT, OR 1.09, 95%CI 1.02-1.17, P = .018). CONCLUSIONS: Higher thrombus density was the independent predictor for SE. Further studies are needed to investigate its role in the optimization of thrombectomy strategy.