Mastorakos, Panagiotis

Abstract Purpose Although the Woven EndoBridge (WEB) device is increasingly used for the treatment of wide-neck intracranial aneurysms, including in the acute rupture setting, comparative evidence assessing the impact of rupture status remains limited. This study compared angiographic, safety, and clinical outcomes between ruptured and unruptured intracranial aneurysms treated with WEB. Methods We conducted a retrospective analysis of prospectively collected data from the multicenter cohort registry WorldWideWEB, including consecutive adult patients with intracranial aneurysms treated with the WEB. Patients were stratified into groups of ruptured and unruptured aneurysms. Propensity score matching was used to balance baseline characteristics between both groups. Retreatment rate was the primary outcome. Secondary outcomes included mRS, safety events (thromboembolic complications) and angiographic outcomes (periprocedurally and last follow-up). Results Among 1,220 patients, 342 (28.0%) presented with ruptured aneurysms. There was no significant difference in the rate of thromboembolic complications between groups (11.8% vs 5.9%, p = 0.056). At follow-up, adequate occlusion was lower (82.2% vs 93.3%, p < 0.002) and functional outcomes were worse (mRS ≥2 in 34.1% vs 21.9%, p = 0.012) among patients with ruptured aneurysms. Periprocedural adequate occlusion (53.3% vs 53.8%, p>0.9) and retreatment rates (11.8% vs 7.1%, p = 0.14) did not differ between groups after matching. Conclusion Ruptured aneurysms demonstrated expected inferior follow-up functional and angiographic outcomes when compared with unruptured aneurysms, but no difference in retreatment rate and procedural safety. These findings support WEB as a safe and effective treatment option for appropriately selected ruptured intracranial aneurysms in routine clinical practice.

Introduction: Optimizing patient selection and time-to-intervention will be crucial to the success of future clinical trials seeking to implement therapies and improve intracerebral hemorrhage (ICH) patient outcomes. Automated and accurate ICH and perihematomal edema (PHE) volumetry carries significant potential to strengthen trials targeting ICH and PHE expansion. Aims: The Quantification of Hematoma and Perihematomal Edema Volumes in Intracerebral Hemorrhage (QUANTUM) trial was designed with aims of (1) validating a fully automated artificial intelligence (AI) method for supratentorial, spontaneous ICH and PHE volumetry against the manual and semiautomated quantification methods and (2) establishing a model framework for the translation of AI technology through conduct of a clinical trial under the equivalence hypothesis paradigm. Methods: This trial was a prospective, randomized, clinical study with blinded outcome assessment. Six independent raters were randomized in a 1:1 ratio to ICH and PHE volumetry from non-contrast CT scans in the Virtual International Stroke Trials Archive with either the semiautomated or manual quantification method. The primary outcomes were equivalence between (1)ICH volume measurements on admission (<24h from symptom onset) for the manual versus the fully automated or the sem-automated quantification methods, and (2)PHE volume measurements on day 3 (72±12h from symptom onset) for the manual versus the fully automated or the semiautomated quantification methods. The required sample size was 126 ICH and 126 PHE measurements, based upon a significance level of 0.025 to account for the two equivalence tests. Results: The geometric mean relative discrepancies between the fully automated and the manual ICH and PHE volume measurements did not cross the pre-specified 10% equivalence margin. The geometric mean relative discrepancies between the semiautomated and the manual ICH and PHE volume measurements did cross the pre-specified 10% equivalence margin. The fully automated method (mean 10.0±2.7s/scan) was significantly faster than the manual (mean 189±199 s/scan; P <0.001) and semiautomated (mean 79±68s/scan; P <0.001) methods. Conclusions: ICH and PHE volumes quantified by AI could replace clinician measurements within a 10% error margin and with substantially greater efficiency. The semiautomated method could not replace manual measurements. This trial demonstrated feasibility of the equivalence hypothesis framework for AI validation studies.

Background The Woven EndoBridge (WEB) device represents an innovative solution for cerebral aneurysm occlusion, particularly for challenging wide-neck bifurcation aneurysms. However, factors affecting sustained occlusion remain poorly understood. We utilized machine learning to attempt to identify predictors of favorable long-term outcomes following WEB treatment. Methods In this multicenter retrospective study, we collected patient demographics, aneurysm characteristics, procedural details, and clinical outcomes. The primary endpoint was improvement in occlusion status, defined as maintained Raymond-Roy Occlusion Classification (RROC) grade 1, or improvement from grade 2 to 1, or from grade 3 to either 2 or 1 on final angiographic follow up. The dataset was split into training (75%) and validation (25%) sets. The CatBoost algorithm was selected based on performance metrics, with Shapley Additive exPlanations (SHAP) values calculated to determine feature importance. Furthermore, a multivariable binomial logistic regression model was performed to validate machine learning findings. Results Among 720 aneurysms from 36 hospitals, 84% showed improvement in occlusion at follow up. Both machine learning and multivariable logistic regression identified aneurysm height as the most consistent correlate of nonimprovement (odds ratio (OR) 0.90 per mm, p = 0.022). In the CatBoost model, the highest-ranking features by SHAP included aneurysm height, patient age, treatment acuity, ACom location, WEB-SLS device, bifurcation anatomy, aneurysm multiplicity, baseline modified Rankin Scale, access route, and partial thrombosis. Conclusions Machine-learning and regression analyses identified consistent predictors of occlusion improvement after WEB treatment, with aneurysm height most strongly linked to nonimprovement. These insights may guide patient selection and follow up. Findings require cautious interpretation and external validation in larger cohorts.

Background The Woven EndoBridge (WEB) device is a prevalent treatment for intracranial aneurysms. While many studies have assessed the obliteration rate post-WEB embolization, few have focused on long-term outcomes in partially thrombosed aneurysms. Objective To assess whether partially thrombosed aneurysms are at higher risk of recurrence or retreatment following WEB embolization compared with non-thrombosed aneurysms. Methods We evaluated data from 22 academic institutions, focusing on previously untreated cerebral aneurysms treated with the WEB device. Logistic regression was utilized to analyze factors predicting long-term aneurysm obliteration and retreatment necessity. Results Among 1303 patients, 26 presented with a partially thrombosed aneurysm. In the partially thrombosed group, the mean aneurysm maximal diameter was 10.7±4 mm with a neck ratio of 1.99±1.19 mm, larger than in the control group where the mean aneurysm maximal diameter was 6.81±2.37 mm with a neck ratio of 1.64±0.51 mm (P<0.001 for both maximal diameter and neck ratio). At the final follow-up, partially thrombosed aneurysms treated by the WEB device had a 38.5% retreatment rate, compared with 7.0% for non-thrombosed aneurysms (P<0.001). Among partially thrombosed aneurysms, the Raymond-Roy type IIIa/b occlusion rate was higher (38.5% vs 9.9%, P<0.001). On multivariate analysis, partially thrombosed aneurysms compared with non-thrombosed aneurysms had an increased rate of retreatment (OR 3.64, 95% CI 1.28 to 10.1). Conclusion Partially thrombosed aneurysms are associated with a poorer occlusion rate and a higher rate of retreatment following WEB embolization. For partially thrombosed aneurysms, the WEB device appears suboptimal as a first-line treatment, and therefore alternative techniques should be prioritized.

OBJECTIVE Tobacco smoking is among the factors known to significantly augment the risk of untreated intracranial aneurysm (IA) growth and rupture. Smoking appears to have a variable effect on different endovascular treatment modalities. The impact of smoking on the safety, efficacy, and outcomes of Woven EndoBridge (WEB) device use for wide-neck IAs has not been evaluated. This study aimed to investigate the outcomes of WEB devices by smoking status. METHODS A retrospective multicenter analysis was conducted on the data of patients from 36 sites worldwide treated with the WEB device for intracranial saccular aneurysms. Patients were stratified based on smoking status (current, former, and never smokers). The Student t-test and chi-square test were performed for continuous and categorical variables, respectively. Multivariable logistic regression was used to adjust for confounders. RESULTS Of 1376 patients with available smoking status, 504 were current smokers, 358 were former smokers, and 514 were never smokers. Upon adjusting for significant confounders, no association was found between smoking and recurrence outcomes (OR 1.39, 95% CI 0.69–2.80; p = 0.36), thromboembolic and hemorrhagic complications, and mortality among IAs treated with the WEB device. There was no statistically significant difference in outcomes between former and never smokers (OR 1.23, 95% CI 0.70–2.18; p = 0.46). The location of aneurysms differed between smoking groups, with former smokers having more anterior circulation aneurysms compared with current and never smokers (99.0% vs 96.9% vs 95.3%; p = 0.01). In terms of clinical symptoms, headache and dizziness were more common in the never smokers compared with current and former smokers (13.9% vs 8.9% vs 7.7%, p = 0.01). CONCLUSIONS This large-scale study suggests no significant correlation between smoking and the recurrence of IAs treated with the WEB device. Biological studies are warranted to better understand the biological impact of smoking on the growth and rupture of treated IAs.

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 Endovascular treatment with the woven endobridge (WEB) device has been widely utilized for managing intracranial aneurysms. However, predicting the probability of achieving adequate occlusion (Raymond–Roy classification 1 or 2) remains challenging. Objective Our study sought to develop and validate a predictive calculator for adequate occlusion using the WEB device via data from a large multi-institutional retrospective cohort. Methods We used data from the WorldWide WEB Consortium, encompassing 356 patients from 30 centers across North America, South America, and Europe. Bivariate and multivariate regression analyses were performed on a variety of demographic and clinical factors, from which predictive factors were selected. Calibration and validation were conducted, with variance inflation factor (VIF) parameters checked for collinearity. Results A total of 356 patients were included: 124 (34.8%) were male, 108 (30.3%) were elderly (≥65 years), and 118 (33.1%) were current smokers. Mean maximum aneurysm diameter was 7.09 mm (SD 2.71), with 112 (31.5%) having a daughter sac. In the multivariate regression, increasing aneurysm neck size (OR 0.706 [95% CI: 0.535–0.929], p = 0.13) and partial aneurysm thrombosis (OR 0.135 [95% CI: 0.024–0.681], p = 0.016) were found to be the only statistically significant variables associated with poorer likelihood of achieving occlusion. The predictive calculator shows a c-statistic of 0.744. Hosmer–Lemeshow goodness-of-fit test indicated a satisfactory model fit with a p-value of 0.431. The calculator is available at: https://neurodx.shinyapps.io/WEBDEVICE/ . Conclusion The predictive calculator offers a substantial contribution to the clinical toolkit for estimating the likelihood of adequate intracranial aneurysm occlusion by WEB device embolization.

OBJECTIVE This study was conducted to investigate the impact of antiplatelet administration in the periprocedural period on the occurrence of thromboembolic complications (TECs) in patients undergoing treatment using the Woven EndoBridge (WEB) device for intracranial wide-necked bifurcation aneurysms. The primary objective was to assess whether the use of antiplatelets in the pre- and postprocedural phases reduces the likelihood of developing TECs, considering various covariates. METHODS A retrospective multicenter observational study was conducted within the WorldWideWEB Consortium and comprised 38 academic centers with endovascular treatment capabilities. Univariable and multivariable logistic regression analyses were performed to determine the association between antiplatelet use and TECs, adjusting for covariates. Missing predictor data were addressed using multiple imputation. RESULTS The study comprised two cohorts: one addressing general thromboembolic events and consisting of 1412 patients, among whom 103 experienced TECs, and another focusing on symptomatic thromboembolic events and comprising 1395 patients, of whom 50 experienced symptomatic TECs. Preprocedural antiplatelet use was associated with a reduced likelihood of overall TECs (OR 0.32, 95% CI 0.19–0.53, p < 0.001) and symptomatic TECs (OR 0.49, 95% CI 0.25–0.95, p = 0.036), whereas postprocedural antiplatelet use showed no significant association with TECs. The study also revealed additional predictors of TECs, including stent use (overall: OR 4.96, 95% CI 2.38–10.3, p < 0.001; symptomatic: OR 3.24, 95% CI 1.26–8.36, p = 0.015), WEB single-layer sphere (SLS) type (overall: OR 0.18, 95% CI 0.04–0.74, p = 0.017), and posterior circulation aneurysm location (symptomatic: OR 18.43, 95% CI 1.48–230, p = 0.024). CONCLUSIONS The findings of this study suggest that the preprocedural administration of antiplatelets is associated with a reduced likelihood of TECs in patients undergoing treatment with the WEB device for wide-necked bifurcation aneurysms. However, postprocedural antiplatelet use did not show a significant impact on TEC occurrence.