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Background The effects of thrombus imaging characteristics on procedural and clinical outcomes after ischemic stroke are increasingly being studied. These thrombus characteristics -- for eg, size, location, and density -- are commonly analyzed as separate entities. However, it is known that some of these thrombus characteristics are strongly related. Multicollinearity can lead to unreliable prediction models. We aimed to determine the distribution, correlation and clustering of thrombus imaging characteristics based on a large dataset of anterior-circulation acute ischemic stroke patients. Methods We measured thrombus imaging characteristics in the MR CLEAN Registry dataset, which included occlusion location, distance from the intracranial carotid artery to the thrombus (DT), thrombus length, density, perviousness, and clot burden score (CBS). We assessed intercorrelations with Spearman's coefficient (ρ) and grouped thrombi based on 1) occlusion location and 2) thrombus length, density and perviousness using unsupervised clustering. Results We included 934 patients, of which 22% had an internal carotid artery (ICA) occlusion, 61% M1, 16% M2, and 1% another occlusion location. All thrombus characteristics were significantly correlated. Higher CBS was strongly correlated with longer DT (ρ=0.67, p<0.01), and moderately correlated with shorter thrombus length (ρ=-0.41, p<0.01). In more proximal occlusion locations, thrombi were significantly longer, denser, and less pervious. Unsupervised clustering analysis resulted in four thrombus groups; however, the cohesion within and distinction between the groups were weak. Conclusions Thrombus imaging characteristics are significantly intercorrelated -- strong correlations should be considered in future predictive modeling studies. Clustering analysis showed there are no distinct thrombus archetypes -- novel treatments should consider this thrombus variability. [ABSTRACT FROM AUTHOR]

Good collateral status in acute ischemic stroke patients is an important indicator for good outcomes. Perfusion imaging potentially allows for the simultaneous assessment of local perfusion and collateral status. We combined multiple CTP parameters to evaluate a CTP-based collateral score. We included 85 patients with a baseline CTP and single-phase CTA images from the MR CLEAN Registry. We evaluated patients' CTP parameters, including relative CBVs and tissue volumes with several time-to-maximum ranges, to be candidates for a CTP-based collateral score. The score candidate with the strongest association with CTA-based collateral score and a 90-day mRS was included for further analyses. We assessed the association of the CTP-based collateral score with the functional outcome (mRS 0–2) by analyzing three regression models: baseline prognostic factors (model 1), model 1 including the CTA-based collateral score (model 2), and model 1 including the CTP-based collateral score (model 3). The model performance was evaluated using C-statistic. Among the CTP-based collateral score candidates, relative CBVs with a time-to-maximum of 6–10 s showed a significant association with CTA-based collateral scores (p = 0.02) and mRS (p = 0.05) and was therefore selected for further analysis. Model 3 most accurately predicted favorable outcomes (C-statistic = 0.86, 95% CI: 0.77–0.94) although differences between regression models were not statistically significant. We introduced a CTP-based collateral score, which is significantly associated with functional outcome and may serve as an alternative collateral measure in settings where MR imaging is not feasible. [ABSTRACT FROM AUTHOR]

Background Machine learning algorithms hold the potential to contribute to fast and accurate detection of large vessel occlusion (LVO) in patients with suspected acute ischemic stroke. We assessed the diagnostic performance of an automated LVO detection algorithm on CT angiography (CTA). Methods Data from the MR CLEAN Registry and PRESTO were used including patients with and without LVO. CTA data were analyzed by the algorithm for detection and localization of LVO (intracranial internal carotid artery (ICA)/ICA terminus (ICA-T), M1, or M2). Assessments done by expert neuroradiologists were used as reference. Diagnostic performance was assessed for detection of LVO and per occlusion location by means of sensitivity, specificity, and area under the curve (AUC). Results We analyzed CTAs of 1110 patients from the MR CLEAN Registry (median age (iQR) 71 years (60-80); 584 men; 1110 with LVO) and of 646 patients from PRESTO (median age (IQR) 73 years (62-82); 358 men; 141 with and 505 without LVO). For detection of LVO, the algorithm yielded a sensitivity of 89% in the MR CLEAN Registry and a sensitivity of 72%, specificity of 78%, and AUC of 0.75 in PRESTO. Sensitivity per occlusion location was 88% for ICA/ICA-T, 94% for M1, and 72% for M2 occlusion in the MR CLEAN Registry, and 80% for ICA/ICA-T, 95% for M1, and 49% for M2 occlusion in PRESTO. Conclusion The algorithm provided a high detection rate for proximal LVO, but performance varied significantly by occlusion location. Detection of M2 occlusion needs further improvement. [ABSTRACT FROM AUTHOR]

Background: Endovascular treatment (EVT) has greatly improved the prognosis of acute ischemic stroke (AIS) patients with a proximal intracranial large vessel occlusion (LVO) of the anterior circulation. Currently, there is clinical equipoise concerning the added benefit of intravenous alteplase administration (IVT) prior to EVT. The aim of this study is to assess the efficacy and safety of omitting IVT before EVT in patients with AIS caused by an anterior circulation LVO.Methods: MR CLEAN-NO IV is a multicenter randomized open-label clinical trial with blinded outcome assessment (PROBE design). Patients ≥ 18 years of age with a pre-stroke mRS < 3 with an LVO confirmed on CT angiography/MR angiography eligible for both IVT and EVT are randomized to receive either IVT (0.9 mg/kg) followed by EVT, or direct EVT in a 1:1 ratio. The primary objective is to assess superiority of direct EVT. Secondarily, non-inferiority of direct EVT compared to IVT before EVT will be explored. The primary outcome is the score on the modified Rankin Scale at 90 days. Ordinal regression with adjustment for prognostic variables will be used to estimate treatment effect. Secondary outcomes include reperfusion graded with the eTICI scale after EVT and stroke severity (National Institutes of Health Stroke Scale) at 24 h. Safety outcomes include intracranial hemorrhages scored according to the Heidelberg criteria. A total of 540 patients will be included.Discussion: IVT prior to EVT might facilitate early reperfusion before EVT or improved reperfusion rates during EVT. Conversely, among other potential adverse effects, the increased risk of bleeding could nullify the beneficial effects of IVT. MR CLEAN-NO IV will provide insight into whether IVT is still of added value in patients eligible for EVT.Trial Registration: www.isrctn.com : ISRCTN80619088 . Registered on 31 October 2017. [ABSTRACT FROM AUTHOR]

Approximately 10% of all cases of deep vein thrombosis (DVT) occur in the upper extremities. The most common secondary cause of upper-extremity DVT (UEDVT) is the presence of a venous catheter. Primary UEDVT is far less common and usually occurs in patients with anatomic abnormalities of the costoclavicular space causing compression of the subclavian vein, called venous thoracic outlet syndrome (VTOS). Subsequently, movement of the arm results in repetitive microtrauma to the vein and its surrounding structures causing apparent ‘spontaneous’ thrombosis, or Paget-Schrötter syndrome. Treatment of UEDVT aims at elimination of the thrombus, thereby relieving acute symptoms, and preventing recurrence. Initial management for all UEDVT patients consists of anticoagulant therapy. In patients with Paget-Schrötter syndrome the underlying VTOS necessitates a more aggressive management strategy. Several therapeutic options exist, including catheter-directed thrombolysis, surgical decompression through first rib resection, and percutaneous transluminal angioplasty of the vein. However, several controversies exist regarding their indication and timing. [ABSTRACT FROM AUTHOR]

Background and Objective: Mechanical thrombectomy is a minimally invasive procedure that aims at removing the occluding thrombus from the vasculature of acute ischemic stroke patients. Thrombectomy success and failure can be studied using in-silico thrombectomy models. Such models require realistic modeling steps to be effective. We here present a new approach to model microcatheter tracking during thrombectomy., Methods: For 3 patient-specific vessel geometries, we performed finite-element simulations of the microcatheter tracking (1) following the vessel centerline (centerline method) and (2) as a one-step insertion simulation, where the microcatheter tip was advanced along the vessel centerline while its body was free to interact with the vessel wall (tip-dragging method). Qualitative validation of the two tracking methods was performed with the patient's digital subtraction angiography (DSA) images. In addition, we compared simulated thrombectomy outcomes (successful vs unsuccessful thrombus retrieval) and maximum principal stresses on the thrombus between the centerline and tip-dragging method., Results: Qualitative comparison with the DSA images showed that the tip-dragging method more realistically resembles the patient-specific microcatheter-tracking scenario, where the microcatheter approaches the vessel walls. Although the simulated thrombectomy outcomes were similar in terms of thrombus retrieval, the thrombus stress fields (and the associated fragmentation of the thrombus) were strongly different between the two methods, with local differences in the maximum principal stress curves up to 84%., Conclusions: Microcatheter positioning with respect to the vessel affects the stress fields of the thrombus during retrieval, and therefore, may influence thrombus fragmentation and retrieval in-silico thrombectomy., Competing Interests: Declaration of Competing Interest HAM reports co-founder and shareholder of Nicolab, a company that focuses on the use of artificial intelligence for medical image analysis. CBLMM reports grants from the European Commission during the conduct of the study; grants from CVON/ Dutch Heart Foundation, TWIN Foundation, Healthcare Evaluation Netherlands, and Stryker, outside the submitted work; and shareholder of Nicolab. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: We evaluated data from all patients in the Netherlands who underwent endovascular treatment for acute ischemic stroke in the past 3.5 years, to identify nationwide trends in time to treatment and procedural success, and assess their effect on clinical outcomes., Methods: We included patients with proximal occlusions of the anterior circulation from the second and first cohorts of the MR CLEAN (Multicenter Randomized Clinical trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry (March 2014 to June 2016; June 2016 to November 2017, respectively). We compared workflow times and rates of successful reperfusion (defined as an extended Thrombolysis in Cerebral Infarction score of 2B-3) between cohorts and chronological quartiles (all included patients stratified in chronological quartiles of intervention dates to create equally sized groups over the study period). Multivariable ordinal logistic regression was used to assess differences in the primary outcome (ordinal modified Rankin Scale at 90 days)., Results: Baseline characteristics were similar between cohorts (second cohort n=1692, first cohort n=1488) except for higher age, poorer collaterals, and less signs of early ischemia on computed tomography in the second cohort. Time from stroke onset to groin puncture and reperfusion were shorter in the second cohort (median 185 versus 210 minutes; P <0.001 and 236 versus 270 minutes; P <0.001, respectively). Successful reperfusion was achieved more often in the second than in the first cohort (72% versus 66%; P <0.001). Functional outcome significantly improved (adjusted common odds ratio 1.23 [95% CI, 1.07-1.40]). This effect was attenuated by adjustment for time from onset to reperfusion (adjusted common odds ratio, 1.12 [95% CI, 0.98-1.28]) and successful reperfusion (adjusted common odds ratio, 1.13 [95% CI, 0.99-1.30]). Outcomes were consistent in the analysis per chronological quartile., Conclusions: Clinical outcomes after endovascular treatment for acute ischemic stroke in routine clinical practice have improved over the past years, likely resulting from improved workflow times and higher successful reperfusion rates.

Background: The value of administering intravenous alteplase before endovascular treatment (EVT) for acute ischemic stroke has not been studied extensively, particularly in non-Asian populations., Methods: We performed an open-label, multicenter, randomized trial in Europe involving patients with stroke who presented directly to a hospital that was capable of providing EVT and who were eligible for intravenous alteplase and EVT. Patients were randomly assigned in a 1:1 ratio to receive EVT alone or intravenous alteplase followed by EVT (the standard of care). The primary end point was functional outcome on the modified Rankin scale (range, 0 [no disability] to 6 [death]) at 90 days. We assessed the superiority of EVT alone over alteplase plus EVT, as well as noninferiority by a margin of 0.8 for the lower boundary of the 95% confidence interval for the odds ratio of the two trial groups. Death from any cause and symptomatic intracerebral hemorrhage were the main safety end points., Results: The analysis included 539 patients. The median score on the modified Rankin scale at 90 days was 3 (interquartile range, 2 to 5) with EVT alone and 2 (interquartile range, 2 to 5) with alteplase plus EVT. The adjusted common odds ratio was 0.84 (95% confidence interval [CI], 0.62 to 1.15; P = 0.28), which showed neither superiority nor noninferiority of EVT alone. Mortality was 20.5% with EVT alone and 15.8% with alteplase plus EVT (adjusted odds ratio, 1.39; 95% CI, 0.84 to 2.30). Symptomatic intracerebral hemorrhage occurred in 5.9% and 5.3% of the patients in the respective groups (adjusted odds ratio, 1.30; 95% CI, 0.60 to 2.81)., Conclusions: In a randomized trial involving European patients, EVT alone was neither superior nor noninferior to intravenous alteplase followed by EVT with regard to disability outcome at 90 days after stroke. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by the Collaboration for New Treatments of Acute Stroke consortium and others; MR CLEAN-NO IV ISRCTN number, ISRCTN80619088.)., (Copyright © 2021 Massachusetts Medical Society.)

Background and Aims: Distinct subtypes of intracranial carotid artery calcification (ICAC) have been found (i.e., medial and intimal), which may differentially be associated with the formation of collaterals. We investigated the association of ICAC subtype with collateral status in patients undergoing endovascular thrombectomy (EVT) for ischemic stroke. We further investigated whether ICAC subtype modified the association between collateral status and functional outcome., Methods: We used data from 2701 patients with ischemic stroke undergoing EVT. Presence and subtype of ICAC were assessed on baseline non-contrast CT. Collateral status was assessed on baseline CT angiography using a visual scale from 0 (absent) to 3 (good). We investigated the association of ICAC subtype with collateral status using ordinal and binary logistic regression. Next, we assessed whether ICAC subtype modified the association between collateral status and functional outcome (modified Rankin Scale, 0-6)., Results: Compared to patients without ICAC, we found no association of intimal or medial ICAC with collateral status (ordinal variable). When collateral grades were dichotomized (3 versus 0-2), we found that intimal ICAC was significantly associated with good collaterals in comparison to patients without ICAC (aOR, 1.41 [95%CI:1.06-1.89]) or with medial ICAC (aOR, 1.50 [95%CI:1.14-1.97]). The association between higher collateral grade and better functional outcome was significantly modified by ICAC subtype (p for interaction = 0.01)., Conclusions: Patients with intimal ICAC are more likely to have good collaterals and benefit more from an extensive collateral circulation in terms of functional outcome after EVT., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Ischemic brain tissue damage in patients with acute ischemic stroke, as measured by the Alberta Stroke Program Early CT Score (ASPECTS) may be more impactful in older than in younger patients, although this has not been studied. We aimed to investigate a possible interaction effect between age and ASPECTS on functional outcome in acute ischemic stroke patients undergoing endovascular treatment, and compared reperfusion benefit across age and ASPECTS subgroups., Methods: Patients with ischemic stroke from the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands; March 2014-November 2017) were included. Multivariable ordinal logistic regression was performed to obtain effect size estimates (adjusted common odds ratio) on functional outcome (modified Rankin Scale score) for continuous age and granular ASPECTS, with a 2-way multiplicative interaction term (age×ASPECTS). Outcomes in four patient subgroups based on age (< versus ≥ median age [71.8 years]) and baseline ASPECTS (6-10 versus 0-5) were assessed., Results: We included 3279 patients. There was no interaction between age and ASPECTS on modified Rankin Scale ( P =0.925). The highest proportion of modified Rankin Scale 5 to 6 was observed in patients >71.8 years with baseline ASPECTS 0 to 5 (68/107, 63.6%). There was benefit of reperfusion in all age-ASPECTS subgroups. Although the adjusted common odds ratio was lower in patients >71.8 years with ASPECTS 0 to 5 (adjusted common odds ratio, 1.60 [95% CI, 0.66-3.88], n=110), there was no significant difference from the main effect ( P =0.299)., Conclusions: Although the proportion of poor outcomes following endovascular treatment was highest in older patients with low baseline ASPECTS, outcomes did not significantly differ from the main effect. These results do not support withholding endovascular treatment based n a combination of high age and low ASPECTS.

Three patients, 2 women aged 42 and 20 years and a 21-year-old man, presented with painful swelling of the upper extremity. The symptoms developed after activities involving repetitive, excessive use of the upper extremity. Duplex examination and venography showed thrombosis of the subclavian vein. This specific type of thrombosis is known as effort thrombosis or Paget-von Schroetter syndrome. It results from a narrowed thoracic outlet combined with repetitive strenuous use of the upper extremity. All three patients were first treated with thrombolytic therapy using urokinase delivered locally in the thrombus with a catheter. After the thrombus had resolved, a first rib resection was performed to decompress the thoracic outlet. Due to the remaining substantial stenosis and vessel wall irregularity, additional percutaneous transluminal angioplasty was performed. It is important to treat effort thrombosis immediately and adequately. Otherwise, it may lead to a postthrombotic syndrome, which can be severely disabling.