Ghozy, Sherief

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.

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.

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 Acute ischemic stroke arising from medium vessel occlusions (MeVO) poses substantial challenges in treatment and management. This study aims to elucidate the outcomes and factors contributing to achieving excellent recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] 2c–3) versus successful recanalization (mTICI 2b) in patients with MeVO stroke undergoing mechanical thrombectomy (MT). Methods We conducted a multinational study analyzing data from the MAD‐MT (Multicenter Analysis of Distal Medium Vessel Occlusions: Effect of Mechanical Thrombectomy) registry, encompassing 37 centers across North America, Asia, and Europe, collected between September 2017 and July 2023. The study included acute ischemic stroke patients with MeVO treated with MT, with or without intravenous thrombolysis, who achieved mTICI 2b–3 post‐MT. Results Among 1463 patients with successful recanalization (mTICI 2b–3), 523 achieved mTICI 2b recanalization, and 940 achieved mTICI 2c–3. Distal occlusions exhibited higher odds of excellent recanalization compared with proximal MeVO vessel occlusions (odds ratio, 1.58; 95% CI, 1.17–2.15; P = 0.003). Cardioembolic stroke pathogenesis was associated with a higher likelihood of excellent recanalization (1.67; 95% CI, 1.07–2.59; P = 0.018). Patients achieving mTICI 2c–3 recanalization demonstrated lower initial National Institutes of Health Stroke Scale scores, significant improvements in postprocedural National Institutes of Health Stroke Scale shift, and a higher percentage of favorable 90‐day outcomes compared with those with mTICI 2b. However, no significant difference in 90‐day mortality rates was observed. Conclusion This study underscores that among patients with MeVO stroke with successful recanalization (mTICI 2b–3) there is higher likelihood of achieving excellent recanalization (mTICI 2c–3) in distal occlusions and cardioembolic pathogenesis. mTICI 2c–3 scores post‐MT correlate with improved clinical outcomes compared with mTICI 2b, affirming the superiority of excellent recanalization over successful recanalization in patients with MeVO stroke. Further prospective studies and randomized controlled trials are warranted for validation.

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.

Abstract Background: Despite the proven effectiveness of endovascular therapy (EVT) in acute ischemic strokes (AIS) involving anterior circulation large vessel occlusions, isolated posterior cerebral artery (PCA) occlusions (iPCAo) remain underexplored in clinical trials. This study investigates the comparative effectiveness and safety of EVT against medical management (MM) in patients with iPCAo. Methods: This multinational, multicenter propensity score-weighted study analyzed data from the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry, involving 37 centers across North America, Asia, and Europe. We included iPCAo patients treated with either EVT or MM. The primary outcome was the modified Rankin Scale (mRS) at 90 days, with secondary outcomes including functional independence, mortality, and safety profiles such as hemorrhagic complications. Results: A total of 177 patients were analyzed (88 MM and 89 EVT). EVT showed a statistically significant improvement in 90-day mRS scores (OR = 0.55, 95% CI = 0.30–1.00, p = 0.048), functional independence (OR = 2.52, 95% CI = 1.02–6.20, p = 0.045), and a reduction in 90-day mortality (OR = 0.12, 95% CI = 0.03–0.54, p = 0.006) compared to MM. Hemorrhagic complications were not significantly different between the groups. Conclusion: EVT for iPCAo is associated with better neurological outcomes and lower mortality compared to MM, without an increased risk of hemorrhagic complications. Nevertheless, these results should be interpreted with caution due to the study’s observational design. The findings are hypothesis-generating and highlight the need for future randomized controlled trials to confirm these observations and establish definitive treatment guidelines for this patient population.

Background There has been growing data about the association between D-dimer levels and thrombectomy outcomes in acute ischemic stroke patients (AIS) with no cumulative evidence. This systematic review and meta-analysis aim to discuss and analyze the findings of the current studies to provide more robust evidence in this regard. Methods A systematic search was conducted through PubMed, Web of Science, Embase, and Scopus to retrieve all relevant investigations. A meta-analysis was conducted, and the results were presented in odds ratio (ORs) for binary variables and ratio of means (ROM) for continuous variables, each accompanied by its respective 95% confidence intervals (CIs). Results After searching and screening, 14 studies were included. The analysis showed that the low D-dimer group had significantly higher rates of favorable functional outcome (OR: 4.40; 95%CI: 2.65–7.30; p < 0.001, n = 3) and recanalization (OR: 4.13; 95%CI: 1.57–10.84; p = 0.004, n = 3) than the high one. The association between D-dimer levels and first-pass effect and re-occlusion risk was also demonstrated. Eventually, two studies also demonstrated a significant association between high D-dimer levels and deep venous thrombosis and symptomatic intracranial hemorrhage as post-thrombectomy complications. Conclusion Current evidence indicates a significant association between D-dimer levels and post-thrombectomy outcomes in AIS patients. However, current data are remarkably heterogeneous, and additional comparative investigations are needed.

OBJECTIVE The Woven EndoBridge (WEB) device was approved to treat wide-necked bifurcation aneurysms. The device is designed as an intrasaccular flow disruptor covering aneurysm widths up to 10 mm. Although prior studies combined all aneurysm sizes, it is known that aneurysms behave differently in response to endovascular treatment based on their size. Therefore, the authors’ objective was to identify ideal middle cerebral artery (MCA) aneurysm width and neck sizes most suitable for WEB treatment. METHODS The WorldWideWEB consortium is a large multicenter retrospective database that analyzes intracranial aneurysms treated with the WEB device. In this study, all unruptured MCA bifurcation aneurysms with available measurements were included. Cutoff values based on aneurysm width and neck in relation to aneurysm occlusion status were measured using the receiver operating characteristic (ROC) curve. Propensity score matching (PSM) was then used to compare treatment outcomes between aneurysms smaller and larger than the cutoff value for both width and neck size. RESULTS The ideal cutoff values for MCA bifurcation aneurysm width and neck were 6.1 mm and 4.6 mm, respectively. On PSM, 87 matched pairs were compared based on width size (≤ 6.1 mm and > 6.1 mm), and 77 matched pairs were compared based on neck size (≤ 4.6 mm and > 4.6 mm). There was a significant difference in adequate aneurysm occlusion between aneurysms smaller and larger than those cutoff values for both widths (93% vs 76%, p = 0.0017) and neck sizes (90% vs 70%, p = 0.0026). The retreatment rate was also significantly higher for larger aneurysms in both parameters. CONCLUSIONS This study shows that MCA bifurcation aneurysms ≤ 6.1 mm in width and ≤ 4.6 mm in neck size are significantly better candidates for WEB treatment, leading to improved occlusion status and reduced retreatment rate, which are important considerations when using WEB devices.

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.

Background Cerebral sinus venous thrombosis (CSVT) has traditionally been treated medically with systemic anticoagulation. Recent advances in endovascular therapy (EVT) may represent an alternative treatment to medical therapy for CSVT. We conducted a systematic review and meta-analysis to evaluate the use of EVT for CSVT. Methods We conducted a systematic literature review using PubMed, Embase, Scopus, and Web of Science. We included studies that reported outcomes following EVT for CSVT. The primary outcome of interest was rate of modified Rankin Scale (mRS) 0–2. Secondary outcomes of interest were rates of complete, partial, and failed recanalization, mortality, and new or expansion of hematoma. We calculated pooled rates (%) and their corresponding 95% confidence intervals (CIs). Results Thirty-eight studies with 682 patients were included. Rate of mRS 0–2 was 82.6% (95% CI, 75.3%–88.0%). Rate of complete recanalization was 60.9% (95% CI, 49.1%–71.5%), rate of partial recanalization was 34.2% (95% CI, 24.1%–45.9%), and rate of failed recanalization was 5.4% (95% CI, 3.1%–9.2%). Rate of mortality was 6.7% (95% CI, 4.1%–10.8%), and rate of new hematoma or expansion of hematoma was 5.1% (2.9%–8.8%). Conclusions In this systematic review and meta-analysis, EVT for CSVT was associated with favorable rates of mRS 0–2 and recanalization. Furthermore, EVT was associated with a promising safety profile. Future prospective, comparative studies are warranted to assess EVT for CSVT.