Citations

BACKGROUND: The EXCELLENT registry aimed to evaluate the effectiveness of the EMBOTRAP Revascularization Device in an all-comer population in a real-world setting, with a focus on the composition of retrieved clots. METHODS: EXCELLENT is a prospective, global registry of patients with acute ischemic stroke treated with EMBOTRAP as the first-line mechanical thrombectomy device conducted at 34 sites (25 sites contributing clot) from September 2018 to March 2021, utilizing core imaging and central histology laboratories blinded to clinical data, independent 90-day modified Rankin Scale assessment and Clinical Events Committee. RESULTS: After screening 3799 patients, a total of 997 subjects (mean age, 70.0±14.2 years; 51.8% women; 19.7% non-White) were included. The first-pass modified Treatment in Cerebral Infarction (mTICI) ≥2b rate was 64.5% (623/966), first-pass mTICI ≥2c was 39.1% (378/966), and final mTICI ≥2b was 94.5% (931/985). A total of 427/912 (46.8%) patients achieved a 90-day modified Rankin Scale of 0 to 2 or ≤baseline. Embolization to a new territory occurred in 0.2% (2/984), and symptomatic intracranial hemorrhage at 24 hours in 1.6% (16/997). The 90-day mortality was 19.1% (175/918). Device- and/or procedure-related serious adverse events occurred in 5.9% (54/912) through 90 days. The mean RBC percentage of retrieved clots was 45.62±21.372. Among patients who achieved mTICI ≥2b with the first pass, 15.7% (52/331) and 9.7% (32/331), respectively, had RBC-poor (<25%) and RBC-rich (>75%) clots. Patients with no clot retrieved in any procedural pass had a lower percentage of hyperdense or susceptibility vessel sign on baseline imaging (58.9% versus 74.7%; P <0.001), pointing to a potential preprocedure indicator of challenging clot. CONCLUSIONS: The EXCELLENT registry informs real-world practices in mechanical thrombectomy and sheds light on the range of clots effectively retrieved by current technology. This is the first report of detailed patient characteristics where mechanical thrombectomy maneuvers failed to remove any clot material. Although the composition of nonretrievable clots cannot be assessed histologically, the results support the notion that no retrieval may be correlated with imaging findings suggesting clots lower in RBC. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03685578.

Background Aneurysm treatments are crucial to minimize the rupture risk. The underlying molecular processes mediating cellular remodeling, endothelialization, and aneurysm healing following endovascular treatment are poorly understood. The current study aims to explore circulating miRNA as a treatment and outcome-associated biomarkers in patients undergoing endovascular treatment. Methods Patients undergoing endovascular interventions for unruptured intracranial aneurysms, using either flow diverter placement or coil embolization, were enrolled. Blood samples were collected before the intervention and during a follow-up period between 6 and 18 months. Total mRNA/miRNA was isolated from plasma, followed by RNA-seq analysis. Gene Ontology analysis was used to identify pathways linked to altered miRNA expression. Results Twenty-three patients participated, with 13 (56.5%) undergoing flow diversion and 10 (43.5%) coil embolization. The median follow-up sample collection time was 10.70 months (SEM ± 1.32). No significant differences in angiographic occlusion were noted between intervention groups. Differentially expressed miRNAs were not identified between groups at baseline. However, at follow-up, 39 miRNAs were upregulated and 41 were downregulated, independent of intervention. Notably, three miRNAs (miR-4746-5p, miR-4685-3p, and miR-490-3p) were downregulated in the flow diversion group compared to the coil embolization group. Bioinformatics analysis revealed associations with upregulated fluid shear stress, p53, adherens junction pathways, along with downregulated apoptosis pathways. Conclusions This study suggests that fluid shear stress and apoptosis may influence aneurysm healing or thromboembolic events in flow diverter-treated patients. Further research is warranted to elucidate the functional significance of these findings in treatment outcomes, providing valuable insights for improved patient care in intracranial aneurysm management.

Introduction: Intracranial aneurysms are associated with local degradation of the vessel wall resulting in the formation of a blood-filled sac. Approximately 6 million people are estimated to have intercranial saccular aneurysms in the US alone. Most aneurysms remain undetected until rupture, resulting in hemorrhage which carries a high mortality rate (>50%). Flow diverters are placed across the aneurysm neck to divert blood flow away from the sac, preventing rupture once occluded. However, flow diverters carry significant risk for thromboembolism, which is a major cause of morbidity. The elevated risk of thromboembolism is likely due to endothelial injury of the parent artery at the neck of the aneurysm. We hypothesize that the bionanomatrix can promote faster endothelialization and aneurysm occlusion thereby reducing the risk of thromboembolism after flow diverter treatment. Methods: The bionanomatrix is composed of peptide amphiphiles containing endothelial cell adhesive ligand (YIGSR) and a nitric oxide (NO) donor (KKKKK), both components critical for recruiting and retaining endothelial cells on the device. The NO releasing bionanomatrix was coated onto the flow diverters using ultrasonic spray coating, and the NO effects on endothelial cell (EC) and smooth muscle cell (SMC) proliferation on the coated devices was assessed, in vitro, using calcien-AM staining. For the in vivo study, an elastase-induced rabbit aneurysm model was created. The bionanomatrix coated and uncoated flow diverters were implanted into the rabbit aneurysm model for 4 weeks. The coated and uncoated flow diverters were then analyzed for endothelialization, smooth muscle cell proliferation, and aneurysm occlusion by angiography, gross image, and immunohistochemistry analyses. Results: In vitro , the bionanomatrix coated flow diverters significantly enhanced endothelial cell proliferation as well as reduced smooth muscle cell proliferation on the flow diverters compared to the uncoated device. In vivo, after 4 weeks, the bionanomatrix coated flow diverters demonstrated enhanced neck coverage, more complete endothelialization, and reduced smooth muscle thickness on the coated flow diverters compared to the uncoated devices as seen by gross image analysis and histology. Conclusions: The bionanomatrix coated flow diverters can successfully promote faster endothelialization and brain aneurysm occlusion which is critical for reducing the risk of thromboembolism after neurointervention.

Introduction While incidentally discovered covert cerebrovascular diseases (id-CCD) are associated with future stroke, it is not known if patients with id-CCD are prescribed statins. Methods Patients age ≥50 with id-CCD on neuroimaging from 2009 to 2019 with no prior ischaemic stroke, transient ischaemic attack or dementia were identified using natural language processing in a large real-world cohort. Robust Poisson multivariable regression was used to assess statin prescription among patients without prior statins. Results Among 2 41 050 patients, 74 975 patients (31.1%; 4.7% with covert brain infarcts (CBI); 29.0% with white matter disease (WMD)) had id-CCD. 53.5% (95% CI 53.2 to 53.9%) were not on statins within 6 months prior to the scan. Of those, 12.0% (95% CI 11.7 to 12.3%) were prescribed statins in the next 6 months compared with 9.3% (95% CI 9.1 to 9.4%) in those without CCD, a 2.7% (95% CI 2.4 to 3.1%) absolute increase in statin prescription for those with id-CCD. In adjusted analyses, the presence of id-CCD was only associated with minor increases in statin prescription (CBI or WMD (risk ratio (RR) 1.09, 95% CI 1.05 to 1.13), CBI alone (RR 1.34, 95% CI 1.21 to 1.47), WMD alone (RR 1.05, 95% CI 1.01 to 1.09), and CBI and WMD (RR 1.23, 95% CI 1.12 to 1.35)). Discussion Identification of id-CCD is not associated with substantial changes in statin prescription in routine clinical practice.

Background: Acute ischemic stroke (AIS) imposes a major healthcare burden. It is hypothesized that bacterial infection could influence atherosclerosis and thrombus formation, potentially contributing to AIS. Objectives: We aim to systematically review all studies that have investigated the presence of bacterial signatures within thrombi retrieved following mechanical thrombectomy (MT) procedures in patients with AIS. Design: This systematic review is designed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 checklist. Data sources and methods: A comprehensive search was conducted in the Web of Sciences, PubMed, Scopus, and Embase databases to identify relevant studies. Results: The literature search and screening included 11 studies involving 674 patients, with 414 (61.4%) being male and 260 (38.6%) females. Among all the patients, 393 (58.3%) were positive for bacterial presence in their retrieved thrombi. The most utilized technique for bacterial signature detection was bacterial DNA extraction followed by polymerase chain reaction amplification of the 16S rRNA gene sequence. Staphylococcus aureus was the most studied bacteria among the studies analyzed. Conclusion: Bacterial infections and the presence of bacteria within thrombi may significantly contribute to AIS by initiating or exacerbating atherosclerosis or thrombosis. Understanding the mechanisms by which bacteria affect vascular health is crucial for developing effective preventive and therapeutic strategies for stroke patients.

ABSTRACT The mechanisms leading to aneurysm occlusion after treatment with flow‐diverting devices are not fully understood. Flow modification induces thrombus formation within the aneurysm cavity, but fibrin can simultaneously accumulate and cover the device scaffold, leading to further flow modification. However, the interplay and relative importance of these processes are not clearly understood. A computational model of fibrin accumulation and flow modification after flow diversion treatment of cerebral aneurysms has been developed under the guidance of in vitro experiments and observations. The model is based on the loose coupling of flow and transport‐reaction equations that are solved separately by independent codes. Interaction or reactive terms account for thrombin production from prothrombin stimulated by thrombogenic metallic wires and inhibition by antithrombin as well as fibrin production from fibrinogen stimulated by thrombin and flow shear stress, and fibrin adhesion to device wires and already attached fibrin. The computational model was demonstrated and tested on idealized vessel and aneurysm geometries. The model was able to reproduce the salient features of fibrin accumulation after the deployment of flow‐diverting devices in idealized in vitro models of cerebral aneurysms. Namely, fibrin production in regions of high shear stress, initial accumulation at the inflow zone, and progressive occlusion of the device and corresponding flow attenuation. The computational model linking flow dynamics to fibrin production, transport, and adhesion can be used to investigate and better understand the effects that lead to fibrin accumulation and the resulting aneurysm inflow reduction and intra‐aneurysmal flow modulation.

AbstractObjectiveAbout 25% of patients with acute ischemic stroke (AIS) present within the intravenous thrombolytic (IVT) therapeutic window of <4.5 h. This study is to elucidate the safety and efficacy of IVT in the extended therapeutic window (ETW) in patients with AIS.MethodsUsing PRISMA guidelines, a systematic review was conducted using PubMed, Embase, and Scopus. A rigorous risk of bias assessment was conducted using the RoB2 tool. Rates of excellent and good functional outcome (mRS 0–1 and mRS 0–2) at 90 days, symptomatic intracranial hemorrhage (sICH), and mortality at 90 days were pooled using generalized linear mixed model and compared with controls. Meta‐analyses were conducted employing random‐effect models with risk ratio (RR) and 95% confidence intervals (CIs). Subgroup analysis was performed to assess the effect of imaging modalities used for patient selection.ResultsEight randomized controlled trials (n = 2221, 59% male) were included. At 90 days IVT showed higher rates of functional recovery: mRS 0–1: RR 1.21 95% CI 1.1–1.34, p < 0.001, and mRS 0–2: RR 1.11 95% CI 1.03–1.18, p = 0.004. Rate of mortality at 90 day was not different between groups: RR 1.17 95% CI 0.93–1.48, p = 0.17. However, the rate of sICH was higher among IVT group: RR 2.93 95% CI 1.53–5.6, p = 0.001. Subgroup analysis showed higher mRS 0–1 among patients who were selected based on perfusion imaging (p < 0.05).InterpretationThe use of IVT in AIS in ETW is beneficial especially with the use of perfusion imaging for patients' selection.

Background The choice of angiography system could influence the outcomes of mechanical thrombectomy (MT) in the treatment of acute ischemic stroke (AIS), but its impact is not yet well understood. This study aims to compare the clinical and technical outcomes of MT performed with single plane versus biplane angiography systems. Method We conducted a systematic review and meta-analysis, following PRISMA guidelines, by searching PubMed, Embase, Web of Science, and Scopus to include studies on patients with AIS who underwent MT with either single plane or biplane angiography up to May 4, 2024. The primary outcome was a favorable outcome defined as a modified Rankin Scale (mRS) score of 0–2 at 90 days after the procedure. Data were analyzed using a random-effects model and heterogeneity was assessed using the I2 test and Q statistics. Results Five studies with a total of 1562 patients were analyzed. Of these, 68.4% were treated with biplane systems and 31.6% with single plane systems. Single plane angiography was associated with a significantly higher rate of favorable outcomes (OR 1.43; 95% CI 1.13 to 1.80; P<0.01). There were no significant differences in successful recanalization, periprocedural complications, procedure time, total fluoroscopy time, or contrast volume between the two systems. Conclusion While single plane angiography systems may offer slightly better outcomes in MT for AIS, both systems appear equally effective in most clinical and technical perspectives, suggesting that system selection may be more dependent on availability and procedural requirements rather than inherent superiority. Our findings may encourage clinicians to use single-plane angiography in settings where the biplane angiography suite availability is limited, but it should be noted that this observation may have been influenced by selection bias, particularly since the larger studies included in our meta-analysis did not observe this effect in adjusted analyses for potential confounder factors.

Background The angiographic shape of an occlusion, like the clot meniscus sign and the claw sign, has been reported to potentially impact the recanalization rate and clinical outcome in patients undergoing mechanical thrombectomy for acute ischemic strokes. Method Following PRISMA guidelines, a systematic literature search was conducted across PubMed, Scopus, Embase and Web of Science databases. Patients were grouped into clot meniscus/claw sign positive and negative groups based on the definitions obtained from each study. Primary outcomes included technical success, with a meta-analysis performed using a random-effects model to calculate proportions and odds ratios (OR) with 95% confidence intervals (Cl). Results We included seven studies recruiting 1572 patients. The results indicated that the positive and negative groups had comparable first-pass effect (OR 1.95; 95% CI 0.76 to 5.01; P=0.167) and final recanalization (OR 1.36; 95% CI 0.81 to 2.27; P=0.248) rates. However, the rate of having a favorable functional outcome was significantly higher in the positive group than in the negative sign group (OR 1.91; 95% CI 1.25 to 2.92; P<0.003). Within the sign-positive population, the use of contact aspiration was associated with a significantly higher rate of recanalization compared with using a stent retriever (OR 0.18; 95% CI 0.07 to 0.49; P<0.001). This result did not translate into a clinical impact, as both stent retriever and contact aspiration showed comparable rates of functional independence at 3 months (OR 0.22; 95% CI 0.02 to 2.33; P=0.210). Conclusion The presence of the clot meniscus/claw sign is not associated with recanalization outcomes after thrombectomy. However, it might be a good sign to predict which thrombectomy technique might be associated with better recanalization, although current evidence may need further confirmation.