Ghozy, Sherief

Background Cancer-related cerebral embolism due to direct tumor embolization results in a rare acute ischemic stroke with large vessel occlusion (LVO). Despite the established status of mechanical thrombectomy (MT) in LVO management, its effectiveness and safety remains inadequately explored in this specific patient group. Methods We conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, using the Nested Knowledge AutoLit software, encompassing databases like Embase, PubMed, Scopus, and Web of Science, from their inception up to 9 May 2023. Results In the review of 35 studies encompassing 37 cases, mean patient age was 52 years, and 30% were female. Cardiac myxoma (29.7%), cardiac papillary fibroelastoma (16.2%), and squamous cell carcinoma of the lung (8.1%) were the most frequent underlying cancers. The left middle cerebral artery was the most commonly affected occlusion site (24.3%). Of the patients, 67.5% underwent MT alone, while 32.5% received MT combined with intravenous thrombolysis. Successful reperfusion (thrombolysis in cerebral infarction (TICI) 2b–3) was achieved in 89.1% of cases, with 59.4% reaching TICI 3. Functional independence was observed in 29.7% of patients. Conclusion While limitations exist, this comprehensive study highlights the potential benefits of MT in a patient group historically excluded from major trials, warranting further investigation.

Background: Diabetes mellitus (DM) is one of the risk factors for acute ischemic stroke, usually leading to poor prognosis. While DM can reduce the effect of intravenous thrombolysis, metformin can have a positive outcome on AIS patients. The outcomes of stroke in diabetic patients receiving metformin is largely unexplored. In the present study we performed a systematic review to assess the effect of metformin on AIS outcomes in diabetic patients. Methods: A systematic review of literature was performed following PRISMA guideline. PubMed, Embase, Scopus and Web of science were used for the literature search. Study outcomes such as modified Rankin Scale (mRS 0-2) at discharge, symptomatic intracranial hemorrhage (sICH) and 90-day mortality were extracted from the full text and analysis were performed to calculate 95% confidence intervals with pooled odds ratio for all the outcomes. Results: Total of six studies were included in the analysis with a total of 5390 patients taking metformin and 6039 patients without metformin. Favorable mRS of 0-2 was significantly higher among patients taking metformin (OR 1.52, 95% CI 1.21:1.93). The mortality rate was significantly lower in metformin group (OR 0.51, 95% CI 0.42:0.61). These results favor the beneficial effect of taking metformin among DM patients with AIS. Conclusion: Overall, chronic use of metformin seems to be beneficial in AIS patients with DM. There is a trend of favorable outcomes of mRS and Mortality, with a non-statistical significance increase of sICH.

Background: The current evidence supports the benefits of endovascular treatment (EVT) in acute ischemic stroke (AIS) with large vessel occlusion (LVO). The DAWN and DEFUSE-3 trials expanded the EVT window up to 24 hours. A few real-world studies explored EVT outcomes in DAWN/DEFUSE-3 ineligible (NDND) patients. Methods: This meta-analysis investigated EVT outcomes in patients with late-window anterior circulation LVO, including both DAWN/DEFUSE-3 eligible (DD) and NDND patients. Nine studies were included, focusing on study characteristics, risk of bias, and outcomes. Results: Baseline characteristics showed comparable age, gender, comorbidities, NIHSS score, and ASPECTS between DD and NDND patients. NDND patients exhibited larger infarct volumes and higher atrial fibrillation rate. Successful reperfusion rates (TICI 2b-3) were comparable between the two groups (OR= 0.86; 95% CI= 0.40, 1.84; p = 0.689), with significant heterogeneity (I 2 = 73%; P = 0.002). Functional independence (90-day mRS score 0-2) was not significantly different between the two groups (OR= 1.12; 95% CI= 0.77, 1.63; p = 0.552) with notable heterogeneity (I 2 = 46%, p = 0.063). Symptomatic intracranial hemorrhage (sICH) rate was lower in the DD group as compared to NDND patients (OR= 0.49; 95% CI= 0.25, 0.93; p = 0.029) with no heterogeneity (I 2 = 0%, p = 0.552). 90-day mortality was lower in the DD group than in the NDND group (OR= 0.55; 95%-CI= 0.37, 0.82; p = 0.004) with no significant heterogeneity (I 2 = 0%, p = 0.536). Conclusion: While this meta-analysis showed comparable rates of functional independence between DD and NDND patients, the potential bias introduced by the higher rates of sICH and mortality in the latter group should prompt great care when offering EVT to NDND patients. Less restricted EVT eligibility criteria might yield positive outcomes in real-world practice in specific patients. However, increased risks of sICH and mortality in NDND patients warrant further investigation to optimize the risk-benefit balance in expanding EVT eligibility criteria.

Background The Woven Endo-Bridge (WEB) device revolutionized the treatment of wide-necked bifurcation aneurysms by intrasaccular flow diversion. The latest advancement is the WEB-17 system, offering greater flexibility with fewer wires, enabling treatment of smaller distal aneurysms using smaller microcatheters than the WEB-21 system. Methods We conducted a systematic review following preferred reporting items for systematic reviews and meta-analyses guidelines, analyzing data from seven retrospective cohort studies involving 483 aneurysms treated with the WEB-17 device. Statistical analysis computed pooled prevalence rates and 95% confidence intervals using appropriate models for each outcome and R software version 4.3.1 (R Foundation for Statistical Computing, Vienna, Austria). Results Technical success was achieved in 475 out of 483 aneurysms treated with the WEB-17 device, with a success rate of 98.34% (95% confidence interval (CI) = 96.72–99.17). Among the successful cases, 4.97% (95% CI = 1.60–14.39) required adjunctive devices. Adequate occlusion, defined as complete occlusion or neck remnants, was observed in 94.41% (95% CI = 88.17–97.46) of cases. Periprocedural complications were infrequent, with thromboembolic complications occurring in 4.93% (95% CI = 3.29–7.30) of cases, hemorrhagic complications in 1.28% (95% CI = 0.58–2.83), and postprocedural neurologic complications in 0.99% (95% CI = 0.31–3.14). Procedure-related morbidity was observed in 1.71% (95% CI = 0.86–3.39) of cases, and there was one procedure-related mortality reported at 0.21% (95% CI = .03–1.50). Mortality unrelated to the procedure occurred in 1% (95% CI = 0.23–4.15). Conclusion Our findings suggest that the WEB-17 device is associated with a high rate of technical success, favorable angiographic outcomes, and a low rate of periprocedural complications. Further research, including prospective trials, is needed to confirm these findings and establish its safety and efficacy definitively.

Background Distal medium vessel occlusions (DMVOs) and minor strokes represent emerging frontiers in mechanical thrombectomy (MT). Although several randomized clinical trials (RCTs) are underway, the design characteristics of these trials and the specific questions they aim to address have not been extensively explored. This current study sought to investigate the design and data elements reported in active prospective DMVO and minor stroke studies. Methods The ClinicalTrials.gov database was searched for ongoing prospective studies assessing the role of MT in patients with DMVOs or minor strokes. The Nested Knowledge AutoLit platform was utilized to categorize reported outcomes and inclusion/exclusion criteria. Frequencies of reported data elements were extracted from study protocols. Results A total of 10 (8 DMVO and 2 minor stroke) studies enrolling 3520 patients were included. All DMVO studies employ different criteria regarding target occlusion locations. Five DMVO studies use stent retrievers as the first-line thrombectomy technique (62.5%, 5/8), while three studies allow any MT techniques, generally at the operator’s discretion. Four DMVO studies permit intravenous thrombolysis (IVT) utilization in both intervention and control arms (50%, 4/8). The DISTALS trial excludes patients receiving IVT, while the DUSK trial and Tigertriever registry only enroll patients who are ineligible for IVT or for whom IVT failed to achieve reperfusion. DMVO studies exhibit notable heterogeneity in symptom onset duration thresholds for inclusion (<6 hours: 2 studies; <12 hours: 2 studies; <24 hours: 3 studies). Minor stroke trials employ similar inclusion criteria and outcome measures except for symptom duration thresholds for inclusion (8 hours for ENDOLOW and 23 hours for MOSTE). Conclusions There is considerable heterogeneity among active DMVO trials regarding potential target DMVO locations and time thresholds for inclusion based on the last known well time. Furthermore, our review indicates that the utility of aspiration thrombectomy in DMVOs and the advantages of MT without IVT over IVT alone will remain largely unexplored even after completion of active DMVO trials.

AbstractBackground and PurposeThe Alberta Stroke Program Early CT Score (ASPECTS) is a widely used scoring system for evaluating ischemic stroke to determine therapeutic strategy. However, there is variation in the interobserver agreement of ASPECTS. This systematic review and meta‐analysis aimed to investigate the interobserver agreement of total and regional ASPECTS.MethodsA comprehensive search was conducted in the Web of Sciences, PubMed, and Scopus databases to identify relevant studies. Inclusion criteria were studies of noncontrast CT performed within 24 hours of ischemic stroke in the middle cerebral artery territory.ResultsA total of 20 studies, with 3482 patients, reporting interobserver agreement of total and regional ASPECTS were included in the meta‐analysis. The interobserver agreement for total ASPECTS in studies using Kappa coefficient (κ) analysis was substantial (κ = .67, 95% confidence interval [CI]: .57‐.78). In studies using intraclass correlation coefficient (ICC) analysis, agreement was excellent (ICC = .84, 95% CI: .77‐.90). Interobserver agreement was higher in studies in which the observer was unblinded to clinical scenario in both groups (κ = .74, 95% CI: .59‐.89, and ICC = .82, 95% CI: .79‐.85). Per‐region analysis showed that the caudate nucleus had the highest agreement (κ = .68, 95% CI: .60‐.76, and ICC = .84, 95% CI: .74‐.93), while M2 and internal capsule in Kappa studies (κ = .45, 95% CI: .34‐.55 and κ = .47, 95% CI: .28‐.66), and M4 and internal capsule in ICC studies (ICC = .54, 95% CI: .43‐.64 and ICC = .55, 95% CI: .18‐.91) had the lowest agreement.ConclusionThis meta‐analysis demonstrates substantial to excellent interobserver agreement for total ASPECTS, which supports using this method for stroke treatment. However, findings emphasize the need to consider interobserver agreement in specific regions of ASPECTS for treatment decisions.

Background The modified Rankin Scale (mRS) score of ≤2 (functional independence) has been the most common primary endpoint of modern mechanical thrombectomy (MT) trials. However, unlike mRS 0-1, mRS score of 2 indicates disability. An important proportion of the mRS 2 patients are home dependent and report a significant decrease in their quality of life. Purpose To investigate excellent outcome (mRS 0-1) rates after MT. Methods We systematically searched Ovid MEDLINE, Ovid EMBASE, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science databases. Randomized controlled trials (RCTs) investigating the role of modern MT in acute ischemic stroke were screened. Posterior circulation and large-core infarct trials were excluded from the study. The data regarding excellent outcomes (mRS: 0-1), functional independence (mRS: 0-2), and reperfusion were collected. Results Twenty-two RCTs comprising 5692 patients were included in the meta-analysis. The overall mRS 0-1 rate was 31.24% (95% CI = 26.95–36.2). The rate of successful reperfusion was 81.8% (95% CI = 77.93–85.86). MT achieved significantly higher rates of mRS 0-1 compared to standard care alone (OR = 2.04; 95% CI = 1.64–2.55; P-value < 0.001), with no heterogeneity detected among studies (I 2 = 0%; P-value = 0.52). The direct MT and MT plus intravenous thrombolytic treatment groups’ excellent outcome rates were comparable (OR = 0.98; 95% CI = 0.82–1.18; P-value = 0.863). Also, aspiration and stent retriever thrombectomy techniques provided similar excellent outcome rates (OR = 0.76; 95% CI = 0.55–1.05; P-value = 0.141). Conclusions Our results prove the additional benefit of MT over standard care, using a stricter definition for favorable functional outcome. Nearly one-third of patients presenting with large artery occlusion and treated with MT had no disability at 90 days. While this is remarkable, our results also indicate that reperfusion alone is often not enough to prevent disability and underline the need for better neuroprotection strategies.

Background Although direct contact aspiration has emerged as one of the leading techniques for mechanical thrombectomy (MT), there is still ongoing debate about the aspiration/suction pump devices that can optimize recanalization rates. To address this gap, we conducted a meta-analysis comparing the aspiration efficacy of 60 ml syringe and pump devices in benchtop MT models. Methods Systematic literature review was conducted using Medline, Embase, Web of Science, and Scopus in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Outcomes of interest included flow rate and vacuum pressure delivered by a 60 ml syringe and several aspiration pumps. We used a random effects model to calculate the mean difference (MD) with 95% confidence intervals (CIs) and a statistically significant difference was considered as a two-sided p -value of less than 0.05. Results We included six benchtop studies comparing 60 ml syringes and vacuum pumps. Our meta-analysis showed that there were no significant differences in vacuum pressure (MD:0.71inHg, 95% CI: [−0.81;2.23], p = 0.359) and flow rate (MD:0.27 mL/s, 95% CI: [−3,07; 3.61], p = 0.873) between 60 ml syringes and vacuum pumps groups. Conclusions Our study demonstrated comparable performance in terms of vacuum pressure and flow rates between a 60 ml syringe and a heterogeneous combination of commercially available aspiration pumps.

Background The comparison of mechanical thrombectomy (MT) outcomes between patients with the hyperdense middle cerebral artery sign (HMCAS) and non-HMCAS is important to evaluate the impact of this radiological finding on treatment efficacy. This meta-analysis aimed to assess the association between HMCAS and clinical outcomes in patients undergoing thrombectomy, comparing the outcomes over non-HMCAS. Methods A systematic literature search was conducted in PubMed, Ovid Embase, Google Scholar, and Cochrane Library to identify studies on MT outcomes for M1 occlusions of HMCAS over non-HMCAS. Inclusion criteria encompassed modified Rankin Scale (mRS) score, mortality, symptomatic intracranial hemorrhage (sICH), and successful recanalization. Using R software version 4.1.2, we calculated pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CI). Results The meta-analysis was performed for 5 studies with 724 patients. There was no association found between presence of HMCAS and achieving mRS 0–2 (OR = 0.65, 95% CI: 0.29–1.47; p = .544). Mortality analysis also showed no significant association with presence of HMCAS (OR = 0.78, 95% CI: 0.37–1.65; p = .520). No significant difference in sICH risk (OR = 1.54, 95% CI: 0.24–9.66; p = .646) was found between groups. Recanalization analysis showed a non-significant positive association (OR = 1.23, 95% CI: 0.67–2.28; p = .501). Heterogeneity was observed in all analyses. Conclusion Our findings showed that there is no statistically significant difference in mRS scores, mortality, sICH, and recanalization success rates between the HMCAS and non-HMCAS groups.

Background The presence of an outer shell has been recently described as a common feature of acute ischemic stroke (AIS) thrombi. We performed a systematic review of the current literature on shell genesis, structure, and clinical significance. Methods Following PRISMA guidelines, we searched Ovid Cochrane Central Register of Controlled Trials, Embase, Medline, Scopus, and Web of Science for studies reporting the composition and structure of AIS thrombi and clot analogs. Identified studies were added to Covidence software for primary screening. Two reviewers independently screened titles and abstracts followed by full-text screening. Results From 1290 identified studies, 10 were included in this review. Studies using histology/immunohistochemistry/immunofluorescence described fibrin, platelets, von Willebrand factor, and neutrophil extracellular traps as the main components of the shell. Scanning electron microscopy demonstrated a dense, compact fibrin/platelet-rich shell, and a core rich in polyhedrocytes. Microfluidics studies identified highly activated P-selectin-positive platelets and fibrin forming the core while secondary agonists adenosine diphosphate and thromboxane, along with loosely packed P-selectin-negative platelets constituted the shell. Conclusions The composition, compaction, and integrity of the shell may impact thrombolysis and revascularization outcomes. The preponderance of studies supported this conclusion.