Diagnostic accuracy of dual-energy computed tomography to differentiate intracerebral hemorrhage from contrast extravasation after endovascular thrombectomy for acute ischemic stroke: systematic review and meta-analysis.

OBJECTIVES: To assess whether dual-energy computed tomography (DECT), using conventional computed tomography or magnetic resonance imaging as a reference standard, is sufficiently accurate to differentiate intracerebral hemorrhage from contrast extravasation after endovascular thrombectomy for acute ischemic stroke. METHODS: On January 20, 2021, we searched the PubMed Medline, Embase, Web of Science, and Cochrane Library databases. QUADAS-2 was used to assess the risk of bias and applicability. Meta-analyses were performed using a bivariate random-effects model. To explore sources of heterogeneity, meta-regression analyses were performed. Deeks' funnel plot asymmetry test was used to assess publication bias. RESULTS: A total of 7 studies (269 patients, 269 focal areas) were included. The pooled mean sensitivity, specificity, and accuracy of DECT in identifying intracerebral hemorrhage from contrast extravasation after mechanical thrombectomy for acute ischemic stroke were 0.77 (95% confidence interval (CI) 0.29 to 0.96), 1 (95% CI 0.86 to 1), and 0.99 (95% CI 0.98 to 1), respectively. This evidence was of moderate certainty due to the risk of bias. Higgin's I-squared for study heterogeneity was observed for the pooled sensitivity (I2 = 78.88%) and pooled specificity (I2 = 82.12%). Moreover, Deeks' funnel plot asymmetry test revealed no publication bias (p = 0.38). CONCLUSION: DECT shows excellent accuracy and specificity in differentiating intracerebral hemorrhage from contrast extravasation after endovascular thrombectomy for acute ischemic stroke. Nevertheless, there was substantial and moderate heterogeneity among the studies. Future large-scale, prospective cohort studies are warranted to validate our findings. KEY POINTS: • Dual-energy computed tomography shows excellent accuracy and specificity in differentiating intracerebral hemorrhage from contrast extravasation after endovascular thrombectomy for acute ischemic stroke. • Via meta-regression analysis, we found various possible covariates, including the publication date, image analysis, index test time, time of follow-up imaging, and reference standard judgment, that had an important effect on the heterogeneity. • There were no concerns regarding applicability in any of the included studies.

Frequency-Specific Changes of Amplitude of Low-Frequency Fluctuations in Patients with Acute Basal Ganglia Ischemic Stroke.

Objective: The purpose of this study was to investigate the characteristics of different frequency bands in the spontaneous brain activity among patients with acute basal ganglia ischemic stroke (BGIS). Methods: In the present study, thirty-four patients with acute BGIS and forty-four healthy controls were examined by resting-state functional magnetic resonance imaging (rs-fMRI) from May 2019 to December 2020. Two amplitude methods including amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) calculated in three frequency bands (conventional frequency band: 0.01-0.08 Hz; slow-5 frequency band: 0.01-0.027 Hz; and slow-4 frequency band: 0.027-0.073 Hz) were conducted to evaluate the spontaneous brain activity in patients with acute BGIS and healthy controls (HCs). Gaussian Random Field Theory (GRF, voxel p < 0.01 and cluster p < 0.05) correction was applied. The correlation analyses were performed between clinical scores and altered metrics values. Results: Compared to HCs, patients with acute BGIS showed decreased ALFF in the right supramarginal gyrus (SMG) in the conventional and slow-4 bands, increased fALFF in the right middle frontal gyrus (MFG) in the conventional and slow-4 bands, and increased fALFF in the bilateral caudate in the slow-5 frequency band. The fALFF value of the right caudate in the slow-5 frequency band was negatively correlated with the clinical scores. Conclusion: In conclusion, this study showed the alterations in ALFF and fALFF in three frequency bands between patients with acute BGIS and HCs. The results reflected that the abnormal LFO amplitude might be related with different frequency bands and promoted our understanding of pathophysiological mechanism in acute BGIS.

Dynamic Structural and Functional Reorganizations Following Motor Stroke.

BACKGROUND The combined effects of bilateral corticospinal tract (CST) reorganization and interhemispheric functional connectivity (FC) reorganization on motor recovery of upper and lower limbs after stroke remain unknown. MATERIAL AND METHODS A total of 34 patients underwent magnetic resonance imaging (MRI) examination at weeks 1, 4, and 12 after stroke, with a control group of 34 healthy subjects receiving 1 MRI examination. Interhemispheric FC in the somatomotor network (SMN) was calculated using the resting-state functional MRI (rs-fMRI). Fractional anisotropy (FA) of bilateral CST was recorded as a measure of reorganization obtained from diffusion tensor imaging (DTI). After intergroup comparisons, multiple linear regression analysis was used to explore the effects of altered FA and interhemispheric FC on motor recovery. RESULTS Interhemispheric FC restoration mostly occurred within 4 weeks after stroke, and FA in ipsilesional remained CST consistently elevated within 12 weeks. Multivariate linear regression analysis showed that the increase in both interhemispheric FC and ipsilesional CST-FA were significantly correlated with greater motor recovery from week 1 to week 4 following stroke. Moreover, only increased FA of ipsilesional CST was significantly correlated with greater motor recovery during weeks 4 to 12 after stroke compared to interhemispheric FC. CONCLUSIONS Our results show dynamic structural and functional reorganizations following motor stroke, and structure reorganization may be more related to motor recovery at the late subacute phase. These results may play a role in guiding neurological rehabilitation.

Related Network and Differential Expression Analyses Identify Nuclear Genes and Pathways in the Hippocampus of Alzheimer Disease.

BACKGROUND Alzheimer disease (AD) is a typical progressive and destructive neurodegenerative disease that has been studied extensively. However, genetic features and molecular mechanisms underlying AD remain unclear. Here we used bioinformatics to investigate the candidate nuclear genes involved in the molecular mechanisms of AD. MATERIAL AND METHODS First, we used Gene Expression Omnibus (GEO) database to obtain the expression profiles of the mRNAs from hippocampus microarray and identify differentially expressed genes (DEGs) the plier algorithm. Second, functional annotation and visualization of the DEGs were conducted by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Finally, BioGRID, IntAct, STRING, and Cytoscape were utilized to construct a protein-protein interaction (PPI) network. Hub genes were analytically obtained from the PPI network and the microRNA (miRNA)-target network. RESULTS Two hippocampus microarrays (GSE5281 and GSE48350) were obtained from the GEO database, comprising 161 and 253 cases separately. Among these, 118 upregulated genes and 694 downregulated genes were identified. The upregulated DEGs were mainly involved in positive regulation of transcription from RNA polymerase II promoter, positive regulation of cartilage development, and response to wounding. The downregulated DEGs were enriched in chemical synaptic transmission, neurotransmitter secretion, and learning. By combining the results of PPI and miRNA-target network, 8 genes and 2 hub miRNAs were identified, including YWHAZ, DLG4, AGAP2, EGFR, TGFBR3, PSD3, RDX, BRWD1, and hsa-miR-106b-5p and hsa-miR-93-5p. These target genes are highly enriched in various key pathways, such as amyloid-beta formation, regulation of cardiocyte differentiation, and actin cytoskeleton reorganization. CONCLUSIONS In this study, YWHAZ, DLG4, AGAP2, EGFR, TGFBR3, PSD3, RDX, and BRWD1 were identified as candidate genes for future molecular studies in AD, which is expected to improve our understanding of its cause and potential molecular mechanisms. Nuclear genes, DEGs, and related networks identified by integrated bioinformatics analysis may serve as diagnostic and therapeutic targets for AD.

Profiling of the Risk Factors and Designing of a Model to Identify Ischemic Stroke in Patients with Non-Hodgkin Lymphoma: A Multicenter Retrospective Study.

BACKGROUND: The occurrence of ischemic stroke in patients with non-Hodgkin lymphoma (NHL) is not well understood. This study aimed to determine independent risk factors to identity ischemic stroke in non-Hodgkin lymphoma-associated ischemic stroke (NHLAIS) patients. METHODS: This retrospective study was conducted on NHLAIS patients and age- and gender-matched NHL patients. We collected clinical data of patients in both groups and used multiple logistic regression analysis to identify independent risk factors for NHLAIS. A receiver operating characteristic (ROC) analysis was used to establish an identification model based on potential risk factors of NHLAIS. RESULTS: Sixty-three NHLAIS patients and 63 NHL patients were enrolled. Stage III/IV (58/63, 92.1%) and multiple arterial infarcts (44/63, 69.8%) were common among NHLAIS patients. Notably, NHLAIS patients had higher levels of serum fibrinogen (FIB), D-dimer, and ferritin (SF) and prolonged thromboplastin time and prothrombin time (PT) compared with NHL patients (all p < 0.05). Elevated FIB, D-dimer, and SF and prolonged PT were independent risk factors for NHLAIS. The area under the ROC curve of the identification model of NHLAIS patients was largest compared to that of other risk factors (0.838, 95% confidence interval: 0.759-0.899) (p < 0.05). CONCLUSION: This study reveals that elevated serum FIB, D-dimer, and SF and prolonged PT are potential independent risk factors of NHLAIS. The identification model established in this study may help monitor NHL patients who are at high risk of developing NHLAIS.

Core-shell-structured monodisperse copolymer/silica particle suspension and its electrorheological response.

Monodisperse core-shell-structured poly(styrene-co-butyl acrylate-co-[2-(methacryloxy)ethyl] trimethylammonium chloride)/silica (PSBM/SiO2) nanoparticles were applied as new electrorheological (ER) materials in which the particles were dispersed in an insulating oil. These nanoparticles were prepared by the consecutive precipitation of cetyltrimethylammonium bromide and negatively charged tetraethylorthosilicate onto the cationic surfaces of PSBM colloidal particles. The successful deposition of the shell phase of the particles and their morphology was examined by transmission and scanning electron microscopy. Their ER properties were studied with a rotational rheometer under different shear modes: controlled shear rate, steady shear under constant shear rate, and creep test. The silica shell allowed the PSBM/SiO2 particles to exhibit typical ER performance under an applied electric field. The dielectric spectra of the PSBM/SiO2-based ER fluid were also recorded using an LCR meter, which was correlated to the ER performance of the ER fluid.

A comparative study of interhemispheric functional connectivity in patients with basal ganglia ischemic stroke.

Background: Voxel-mirrored homotopic connectivity (VMHC) is utilized to assess the functional connectivity of neural networks by quantifying the similarity between corresponding regions in the bilateral hemispheres of the brain. The exploration of VMHC abnormalities in basal ganglia ischemic stroke (BGIS) patients across different cerebral hemispheres has been limited. This study seeks to establish a foundation for understanding the functional connectivity status of both brain hemispheres in BGIS patients through the utilization of VMHC analysis utilizing resting-state functional magnetic resonance imaging (rs-fMRI). Methods: This study examined a total of 38 patients with left basal ganglia ischemic stroke (LBGIS), 44 patients with right basal ganglia ischemic stroke (RBGIS), and 41 individuals in a healthy control (HC) group. Rs-fMRI studies were performed on these patients, and the pre-processed rs-fMRI data were analyzed using VMHC method. Subsequently, the VMHC values were compared between three groups using a one-way ANOVA and post hoc analysis. Correlation analysis with clinical scales was also conducted. Results: The results indicated that compared to the HC group, significant differences were detected in postcentral gyrus, extending to precentral gyrus in both BGIS groups. Post hoc analysis showed that in the pairwise ROI-based comparison, individuals with LBGIS and RBGIS exhibited reduced VMHC values compared to HC groups. There was no significant difference between the LBGIS and RBGIS groups. In the LBGIS group, the VMHC value showed a negative correlation with NIHSS and a positive correlation with BI. Conclusion: The analysis of VMHC in rs-fMRI revealed a pattern of brain functional remodeling in patients with unilateral BGIS, marked by reduced synchronization and coordination between hemispheres. This may contribute to the understanding of the neurological mechanisms underlying motor dysfunction in these patients.

Frequency specific alterations of the degree centrality in patients with acute basal ganglia ischemic stroke: a resting-state fMRI study.

This study intended to investigate the frequency specific brain oscillation activity in patients with acute basal ganglia ischemic stroke (BGIS) by using the degree centrality (DC) method. A total of 34 acute BGIS patients and 44 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning. The DC values in three frequency bands (conventional band: 0.01-0.08 Hz, slow­4 band: 0.027-0.073 Hz, slow­5 band: 0.01-0.027 Hz) were calculated. A two-sample t-test was used to explore the between-group differences in the conventional frequency band. A two-way repeated-measures analysis of variance (ANOVA) was used to analyze the DC differences between groups (BGIS patients, HCs) and bands (slow­4, slow­5). Moreover, correlations between DC values and clinical indicators were performed. In conventional band, the DC value in the right middle temporal gyrus was decreased in BGIS patients compared with HCs. Significant differences of DC were observed between the two bands mainly in the bilateral cortical brain regions. Compared with the HCs, the BGIS patients showed increased DC in the right superior temporal gyrus and the left precuneus, but decreased mainly in the right inferior temporal gyrus, right inferior occipital gyrus, right precentral, and right supplementary motor area. Furthermore, the decreased DC in the right rolandic operculum in slow-4 band and the right superior temporal gyrus in slow-5 band were found by post hoc two-sample t-test of main effect of group. There was no significant correlation between DC values and clinical scales after Bonferroni correction. Our findings showed that the DC changes in BGIS patients were frequency specific. Functional abnormalities in local brain regions may help us to understand the underlying pathogenesis mechanism of brain functional reorganization of BGIS patients.

Safety and efficacy of intravenous thrombolysis in patients with acute ischemic stroke taking direct oral anticoagulants prior to stroke: a meta-analysis.

BACKGROUND: To assess the safety and efficacy of intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS) taking direct oral anticoagulants (DOACs) prior to stroke. METHODS: Literature was searched in PubMed, Cochrane Library, and Embase until March 13, 2023. The primary outcome was symptomatic intracranial hemorrhage (sICH). Secondary outcomes included excellent outcome (modified Rankin Scale [mRS] 0-1), functional independence (mRS 0-2), and mortality. Odds ratios (OR) with 95% confidence intervals (CI) were estimated using a random-effects model. RESULTS: Five non-randomized studies included 239,879 patients with AIS treated with IVT, with 3400 (1.42%) taking DOACs prior to stroke. The rates of sICH did not differ statistically between patients taking DOACs and those not taking anticoagulants (unadjusted OR 0.98; 95% CI 0.67-1.44; P = 0.92; adjusted OR 0.81; 95% CI 0.64-1.03; P = 0.09). Patients taking DOACs had significantly higher adjusted rates of excellent outcome (adjusted OR 1.22; 95% CI 1.06-1.40; P < 0.01) and functional independence (adjusted OR 1.25; 95% CI 1.10-1.42; P < 0.01) at discharge than those not taking anticoagulants. No significant difference was observed in mortality and other efficacy outcomes between groups after adjustment. CONCLUSION: The meta-analysis indicated that taking DOACs prior to stroke does not significantly increase the risk of sICH in selected patients with AIS treated with IVT. Furthermore, the benefits of IVT in selected patients taking DOACs appear to be comparable to those not taking anticoagulants. Further research is warranted to confirm the findings.

Different doses of tenecteplase vs. alteplase for acute ischemic stroke within 4.5 hours of symptom onset: a network meta-analysis of randomized controlled trials.

Background: The optimal dose of tenecteplase vs. alteplase for acute ischemic stroke (AIS) has yet to be established. Therefore, we included the latest randomized controlled trials (RCT) to assess the efficacy and safety of different doses of tenecteplase vs. alteplase for AIS within 4.5 hours of symptom onset. Methods: Literature was searched in PubMed, Cochrane Library, Embase, Web of Science, and clinical trial registries until February 12, 2023. Odds ratios (OR) with 95% credible intervals (CrI) were estimated using Bayesian network meta-analysis (NMA). Treatments were ranked based on efficacy and safety using the surface under the cumulative ranking curve (SUCRA). Results: Eleven RCTs with 5,475 patients were included. Tenecteplase 0.25 mg/kg and alteplase 0.9 mg/kg had significantly higher rates of excellent functional outcome (tenecteplase: OR, 1.85; 95% CrI, 1.44-2.37; alteplase: OR, 1.60; 95% CrI, 1.29-1.97) and good functional outcome (tenecteplase: OR, 1.54; 95% CrI, 1.19-1.98; alteplase: OR, 1.40; 95% CrI, 1.14-1.74) than placebo, despite an increased risk of symptomatic intracranial hemorrhage. Furthermore, the NMA (OR, 1.16; 95% CrI, 1.01-1.33) and the pairwise meta-analysis (OR, 1.16; 95% CI, 1.02-1.33; P = 0.03) indicated that tenecteplase 0.25 mg/kg was superior to alteplase 0.9 mg/kg in excellent functional outcome. Alteplase 0.9 mg/kg (OR, 2.54; 95% CrI, 1.45-8.08) significantly increased the risk of any intracranial hemorrhage compared with placebo. SUCRA results demonstrated that tenecteplase 0.25 mg/kg ranked first and tenecteplase 0.4 mg/kg ranked last in efficacy outcomes. Conclusions: The NMA indicated that tenecteplase 0.25 mg/kg and alteplase 0.9 mg/kg are safe and significantly improve clinical outcomes in patients with AIS within 4.5 h of symptom onset. Furthermore, tenecteplase 0.25 mg/kg provides more benefit and has the potential to replace alteplase 0.9 mg/kg in AIS treatment. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/index.php, identifier: CRD42022343948.

Regional homogeneity alterations in multifrequency bands in patients with basal ganglia stroke: A resting-state functional magnetic resonance imaging study.

Objective: The aim of this study was to investigate the spontaneous regional neural activity abnormalities in patients with acute basal ganglia ischemic stroke (BGIS) using a multifrequency bands regional homogeneity (ReHo) method and to explore whether the alteration of ReHo values was associated with clinical characteristics. Methods: In this study, 34 patients with acute BGIS and 44 healthy controls (HCs) were recruited. All participants were examined by resting-state functional magnetic resonance imaging (rs-fMRI). The ReHo method was used to detect the alterations of spontaneous neural activities in patients with acute BGIS. A two-sample t-test comparison was performed to compare the ReHo value between the two groups, and a Pearson correlation analysis was conducted to assess the relationship between the regional neural activity abnormalities and clinical characteristics. Results: Compared with the HCs, the patients with acute BGIS showed increased ReHo in the left caudate and subregions such as the right caudate and left putamen in conventional frequency bands. In the slow-5 frequency band, patients with BGIS showed decreased ReHo in the left medial cingulum of BGIS compared to the HCs and other subregions such as bilateral caudate and left putamen. No brain regions with ReHo alterations were found in the slow-4 frequency band. Moreover, we found that the ReHo value of left caudate was positively correlated with the NIHSS score. Conclusion: Our findings revealed the alterations of ReHo in patients with acute BGIS in a specific frequency band and provided a new insight into the pathogenesis mechanism of BGIS. This study demonstrated the frequency-specific characteristics of ReHo in patients with acute BGIS, which may have a positive effect on the future neuroimaging studies.

Utility of Thromboelastography to Identify Hypercoagulability in Lung Cancer Related Ischemic Stroke Patients.

Lung cancer related hypercoagulability could increase the risk of ischemic stroke. Routine coagulation tests may have limited capacity in evaluating hypercoagulability. The aim of this study was to investigate the ability of thromboelastography (TEG) in the identification of hypercoagulability in patients with lung cancer and cryptogenic ischemic stroke (LCIS). Between January 2016 and December 2018, whole citrated blood from LCIS patients (n = 35) and age- and gender-matched lung cancer patients and healthy volunteers were used for TEG and routine coagulation tests. The coagulation indicator and clinical data were compared among the 3 groups. There were 27/35 (77.14%) on TEG and 18/35 (51.43%) on routine coagulation tests of LCIS patients who had evidence of hypercoagulability. The detection rate of hypercoagulability by TEG in LCIS patients was higher than routine coagulation tests (P = 0.018). Comparing with lung cancer patients and healthy controls, LCIS patients have a significantly higher maximum amplitude (MA), fibrinogen, and D-dimer. Multivariate analysis showed that D-dimer and MA were significantly associated with ischemic stroke in lung cancer patients. ROC curve showed that the area under the curve of TEG (0.790 ± 0.048, 95% CI: 0.697-0.864) was significantly higher than routine coagulation tests (0.673 ± 0.059, 95% CI: 0.572-0.763) (P = 0.04) in identifying hypercoagulability in LCIS patients. Therefore, TEG could identify hypercoagulability in LCIS patients and healthy controls. Identification of hypercoagulability in lung cancer patients by TEG may be helpful to prevent the occurrence of LCIS.