Neutrophil Extracellular Traps (NETs) are DNA extracellular networks decorated with histones and granular proteins produced by activated neutrophils. NETs have been identified as major triggers and ...structural factors of thrombosis. A recent study designated extracellular DNA threads from NETs as a potential therapeutic target for improving tissue-type plasminogen activator (tPA)-induced thrombolysis in acute coronary syndrome. The aim of this study was to assess the presence of NETs in thrombi retrieved during endovascular therapy in patients with acute ischemic stroke (AIS) and their impact on tPA-induced thrombolysis.
We analyzed thrombi from 108 AIS patients treated with endovascular therapy. Thrombi were characterized by hematoxylin/eosin staining, immunostaining, and ex vivo enzymatic assay. Additionally, we assessed ex vivo the impact of deoxyribonuclease 1 (DNAse 1) on thrombolysis of AIS thrombi.
Histological analysis revealed that NETs contributed to the composition of all AIS thrombi especially in their outer layers. Quantitative measurement of thrombus NETs content was not associated with clinical outcome or AIS pathogenesis but correlated significantly with endovascular therapy procedure length and device number of passes. Ex vivo, recombinant DNAse 1 accelerated tPA-induced thrombolysis, whereas DNAse 1 alone was ineffective.
This study suggests that thrombus NETs content may be responsible for reperfusion resistance, including mechanical or pharmacological approaches with intravenous tPA, irrespectively of their etiology. The efficacy of a strategy involving an administration of DNAse 1 in addition to tPA should be explored in the setting of AIS.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT02907736.
Over the last decade, there have been significant advances in treatments for anterior ischemic stroke, most notably endovascular thrombectomy (EVT). Despite the success of EVT on overall outcomes, ...intracerebral hemorrhage (ICH) is an important post-procedure complication, often associated with mortality and disability. Hence, predicting the risk of ICH can inform EVT decision making. The ASPECT score is used globally to predict patients' prognosis post-reperfusion therapy. Our objective is to perform a systematic review to collect and synthesize data on the association between ASPECT scores on CT, CTP and DWI-MRI (CT-ASPECT, CTP-ASPECT, and DWI-ASPECT) and the risk of symptomatic ICH after EVT for anterior circulation strokes. We will conduct a broad search of various electronic databases (MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science, and the Cochrane Database of Systematic Reviews) to identify studies published after January 1st, 2012 (commonly accepted as the beginning of the modern EVT era based on availability of stent-retrievers). Two independent reviewers will screen and include studies evaluating associations between symptomatic ICH after thrombectomy and baseline CT-ASPECT, CTP-ASPECT and DWI-ASPECT scores. Data will be extracted to quantify the risk of sICH after EVT based on the ASPECT scoring.
To systematically review the literature and assess agreement on the Alberta Stroke Program Early CT Score (ASPECTS) among clinicians involved in the management of thrombectomy candidates.
Studies ...assessing agreement using ASPECTS published from 2000 to 2015 were reviewed. Fifteen raters reviewed and scored the anonymized CT scans of 30 patients recruited in a local thrombectomy trial during 2 independent sessions, in order to study intrarater and interrater agreement. Agreement was measured using intraclass correlation coefficients (ICCs) and Fleiss kappa statistics for ASPECTS and dichotomized ASPECTS at various cutoff values.
The review yielded 30 articles reporting 40 measures of agreement. Populations, methods, analyses, and results were heterogeneous (slight to excellent agreement), precluding a meta-analysis. When analyzed as a categorical variable, intrarater agreement was slight to moderate (κ = 0.042-0.469); it reached a substantial level (κ > 0.6) in 11/15 raters when the score was dichotomized (0-5 vs 6-10). The interrater ICCs varied between 0.672 and 0.811, but agreement was slight to moderate (κ = 0.129-0.315). Even in the best of cases, when ASPECTS was dichotomized as 0-5 vs 6-10, interrater agreement did not reach a substantial level (κ = 0.561), which translates into at least 5 of 15 raters not giving the same dichotomized verdict in 15% of patients.
In patients considered for thrombectomy, there may be insufficient agreement between clinicians for ASPECTS to be reliably used as a criterion for treatment decisions.
Clinical uncertainty and equipoise are vague notions that play important roles in contemporary problems of medical care and research, including the design and conduct of pragmatic trials. Our goal ...was to show how the reliability study methods normally used to assess diagnostic tests can be applied to particular management decisions to measure the degree of uncertainty and equipoise regarding the use of rival management options.
We first use thrombectomy in acute stroke as an illustrative example of the method we propose. We then review, item by item, how the various design elements of diagnostic reliability studies can be modified in order to measure clinical uncertainty.
The thrombectomy example shows sufficient disagreement and uncertainty to warrant the conduct of additional randomized trials. The general method we propose is that a sufficient number of diverse individual cases sharing a similar clinical problem and covering a wide spectrum of clinical presentations be assembled into a portfolio that is submitted to a variety of clinicians who routinely manage patients with the clinical problem.
Clinicians are asked to independently choose one of the predefined management options, which are selected from those that would be compared within a randomized trial that would address the clinical dilemma. Intra-rater agreement can be assessed at a later time with a second evaluation. Various professional judgments concerning individual patients can then be compared and analyzed using kappa statistics or similar methods. Interpretation of results can be facilitated by providing examples or by translating the results into clinically meaningful summary sentences.
Measuring the uncertainty regarding management options for clinical problems may reveal substantial disagreement, provide an empirical foundation for the notion of equipoise, and inform or facilitate the design/conduct of clinical trials to address the clinical dilemma.
Despite successful recanalization with mechanical thrombectomy (MT) for acute anterior ischemic stroke (AAIS), the number of passes may impact clinical outcome.We analyzed the impact of more than ...three MT passes (>3) in a trial that evaluated contact aspiration (CA) versus stent retriever (SR) as the first-line technique in AAIS.
We included patients with mTICI 2b/3 recanalization after MT for isolated intracranial occlusions. The primary outcome was the percentage of patients with a 90-day modified Rankin Scale (mRS)≤2. Secondary outcomes included overall distribution of 90-day mRS, parenchymal hematoma on 24 hours' brain imaging (PH), and 90-day mortality.
Among the 281 patients included and even after adjustment on time to recanalization, significantly more patients with >3 passes had PH than patients with ≤3 passes in multivariate analysis (adjusted OR, 3.62; 95% CI, 1.55 to 8.44). When the analyses were stratified according to CA vs. SR, patients with >3 passes had a stronger risk of PH than patients with ≤3 passes, only in the SR first-line-treated group (adjusted OR, 9.24; 95% CI, 2.65 to 32.13) and not in the CA first-line-treated group (adjusted RR, 1.73; 95% CI, 0.57 to 5.19). A negative association of borderline significance (P=0.07) between >3 passes and favorable outcome was observed only in SR first-line-treated patients (adjusted OR, 0.33; 95% CI, 0.09 to 1.11).
After three passes of SR and unlike for three passes of CA, there is an increased risk of PH and a trend toward a worse clinical outcome.
Guidelines recommend the use of perfusion computed tomography (CT) to identify emergent large vessel ischemic stroke (ELVIS) patients who are likely to benefit from endovascular thrombectomy (EVT) if ...they present within 6-24 hour (late window) of stroke onset. We aim to determine if the interrater and intrarater reliability among physicians when recommending EVT is significantly different when perfusion CT or non-perfusion CT is reviewed.
A total of 30 non-consecutive patients will be selected from our institutional database comprising 3144 cranial CT scans performed for acute stroke symptoms January 2018 to August 2022. The clinical and radiologic data of the 30 patients will be presented in random order to a group of 29 physicians in two separate sessions at least three weeks apart. In each session, the physicians will evaluate each patient once with automated perfusion images and once without. We will use non-overlapping 95% confidence intervals and difference in agreement classification as criteria to suggest a difference between the Gwet AC1 statistics (κG).
The results obtained from this study, combined with the clinical outcomes data of patients categorized through the two imaging techniques and a cost-effectiveness analysis, will offer a comprehensive evaluation of the clinical utility of perfusion CT neuroimaging. Should there be no significant disparity in the reliability of decisions made by clinicians using the two neuroimaging protocols, it may be necessary to revise existing recommendations regarding neuroimaging in the later time window to align with these findings.
Purpose To evaluate the diagnostic accuracy and reliability of computed tomographic (CT) angiography to distinguish true cervical internal carotid artery (ICA) occlusion from pseudo-occlusion ...(defined as an isolated intracranial thrombus that impedes ascending blood flow) in the context of acute stroke. Materials and Methods This was a retrospective study of patients who underwent thrombectomy with preprocedural CT angiography that helps to demonstrate a lack of attenuation in the cervical ICA on the symptomatic side (24 men and 13 women; mean age, 63 years; age range, 30-86 years). Seven readers, including five neuroradiologists and two interventional neuroradiology fellows, independently reviewed the CT angiography images to assess whether there was true cervical ICA occlusion. Their results were compared with digital subtraction angiography (DSA) as the reference standard. Sensitivity and specificity for detecting true occlusion as well as accuracy and diagnostic odds ratio were calculated, with inter- and intraobserver κ statistics. Results Cervical ICA pseudo-occlusion occurred in 12 of 37 patients (32.4%) with nonattenuation of the cervical ICA on the symptomatic side. Interobserver agreement coefficients did not reach the substantial value of 0.61 for either pairs or groups of readers. The cohort's average sensitivity and specificity was 68% (95% confidence interval CI: 59%, 76%) and 75% (95% CI: 71%, 80%), respectively, with a diagnostic odds ratio of 8 (95% CI: 3, 18) and only fair interobserver agreement (κ = 0.32; 95% CI: 0.16, 0.47). Conclusion In the context of acute ischemic stroke with ipsilateral ICA nonattenuation at single-phase CT angiography, even specialized radiologists may not reliably distinguish true cervical occlusion from pseudo-occlusion.
RSNA, 2017 Online supplemental material is available for this article.
To determine whether the ABC/2 method could accurately and reliably measure infarct volume and guide thrombectomy decision in acute stroke cases presenting with late or unknown onset.
Four physicians ...who routinely use MRI for acute stroke imaging, blinded to the RAPID results, measured the diffusion-weighted imaging (DWI) infarct volume using the ABC/2 method. Measurements with ABC/2 (the index test) were compared with RAPID (the reference standard) to calculate sensitivity, specificity, and accuracy measures for various volume cutpoints. Thrombectomy decisions based on RAPID and raters' measurements using the criteria from the Diffusion-Weighted Imaging or Computerized Tomography Perfusion Assessment With Clinical Mismatch in the Triage of Wake-Up and Late-Presenting Strokes Undergoing Neurointervention With Trevo (DAWN) trial criteria were compared. Interrater and intrarater agreement was measured using kappa statistics.
Accuracy with the ABC/2 method was greater than 80% for each rater and each volume cut point. Interrater and intrarater agreement was substantial to excellent for each volume cut point. Treatment decisions with ABC/2 volume estimations showed strong interrater and intrarater agreement, and led to similar thrombectomy decisions compared with RAPID in more than 85% of cases.
DWI infarct volume measurement using ABC/2 method shows strong accuracy and reliability and may be an acceptable alternative to RAPID software for the application of DAWN criteria for thrombectomy decision-making.
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