Dataset Information

Mass Spectrometry-Based Proteomic Profiling of Thrombotic Material Obtained by Endovascular Thrombectomy in Patients with Ischemic Stroke.

ABSTRACT: Thrombotic material retrieved from acute ischemic stroke (AIS) patients represents a valuable source of biological information. In this study, we have developed a clinical proteomics workflow to characterize the protein cargo of thrombi derived from AIS patients. To analyze the thrombus proteome in a large-scale format, we developed a workflow that combines the isolation of thrombus by endovascular thrombectomy and peptide chromatographic fractionation coupled to mass-spectrometry. Using this workflow, we have characterized a specific proteomic expression profile derived from four AIS patients included in this study. Around 1600 protein species were unambiguously identified in the analyzed material. Functional bioinformatics analyses were performed, emphasizing a clustering of proteins with immunological functions as well as cardiopathy-related proteins with blood-cell dependent functions and peripheral vascular processes. In addition, we established a reference proteomic fingerprint of 341 proteins commonly detected in all patients. Protein interactome network of this subproteome revealed protein clusters involved in the interaction of fibronectin with 14-3-3 proteins, TGF? signaling, and TCP complex network. Taken together, our data contributes to the repertoire of the human thrombus proteome, serving as a reference library to increase our knowledge about the molecular basis of thrombus derived from AIS patients, paving the way toward the establishment of a quantitative approach necessary to detect and characterize potential novel biomarkers in the stroke field.

SUBMITTER: Munoz R

PROVIDER: S-EPMC5855720 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Mass Spectrometry-Based Proteomic Profiling of Thrombotic Material Obtained by Endovascular Thrombectomy in Patients with Ischemic Stroke.

Muñoz Roberto R Santamaría Enrique E Rubio Idoya I Ausín Karina K Ostolaza Aiora A Labarga Alberto A Roldán Miren M Zandio Beatriz B Mayor Sergio S Bermejo Rebeca R Mendigaña Mónica M Herrera María M Aymerich Nuria N Olier Jorge J Gállego Jaime J Mendioroz Maite M Fernández-Irigoyen Joaquín J

International journal of molecular sciences 20180207 2

Thrombotic material retrieved from acute ischemic stroke (AIS) patients represents a valuable source of biological information. In this study, we have developed a clinical proteomics workflow to characterize the protein cargo of thrombi derived from AIS patients. To analyze the thrombus proteome in a large-scale format, we developed a workflow that combines the isolation of thrombus by endovascular thrombectomy and peptide chromatographic fractionation coupled to mass-spectrometry. Using this wo ...[more]

PMID: 29414888

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Project description:ImportanceWhether endovascular thrombectomy (EVT) efficacy for patients with acute ischemic stroke and large cores varies depending on the extent of ischemic injury is uncertain.ObjectiveTo describe the relationship between imaging estimates of irreversibly injured brain (core) and at-risk regions (mismatch) and clinical outcomes and EVT treatment effect.Design, setting, and participantsAn exploratory analysis of the SELECT2 trial, which randomized 352 adults (18-85 years) with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) and large ischemic core to EVT vs medical management (MM), across 31 global centers between October 2019 and September 2022.InterventionEVT vs MM.Main outcomes and measuresPrimary outcome was functional outcome-90-day mRS score (0, no symptoms, to 6, death) assessed by adjusted generalized OR (aGenOR; values >1 represent more favorable outcomes). Benefit of EVT vs MM was assessed across levels of ischemic injury defined by noncontrast CT using ASPECTS score and by the volume of brain with severely reduced blood flow on CT perfusion or restricted diffusion on MRI.ResultsAmong 352 patients randomized, 336 were analyzed (median age, 67 years; 139 [41.4%] female); of these, 168 (50%) were randomized to EVT, and 2 additional crossover MM patients received EVT. In an ordinal analysis of mRS at 90 days, EVT improved functional outcomes compared with MM within ASPECTS categories of 3 (aGenOR, 1.71 [95% CI, 1.04-2.81]), 4 (aGenOR, 2.01 [95% CI, 1.19-3.40]), and 5 (aGenOR, 1.85 [95% CI, 1.22-2.79]). Across strata for CT perfusion/MRI ischemic core volumes, aGenOR for EVT vs MM was 1.63 (95% CI, 1.23-2.16) for volumes ≥70 mL, 1.41 (95% CI, 0.99-2.02) for ≥100 mL, and 1.47 (95% CI, 0.84-2.56) for ≥150 mL. In the EVT group, outcomes worsened as ASPECTS decreased (aGenOR, 0.91 [95% CI, 0.82-1.00] per 1-point decrease) and as CT perfusion/MRI ischemic core volume increased (aGenOR, 0.92 [95% CI, 0.89-0.95] per 10-mL increase). No heterogeneity of EVT treatment effect was observed with or without mismatch, although few patients without mismatch were enrolled.Conclusion and relevanceIn this exploratory analysis of a randomized clinical trial of patients with extensive ischemic stroke, EVT improved clinical outcomes across a wide spectrum of infarct volumes, although enrollment of patients with minimal penumbra volume was low. In EVT-treated patients, clinical outcomes worsened as presenting ischemic injury estimates increased.Trial registrationClinicalTrials.gov Identifier: NCT03876457.

Project description:BackgroundRecent randomized trials have suggested that endovascular thrombectomy (EVT) alone may provide similar functional outcomes as the current standard of care, EVT combined with intravenous alteplase treatment, for acute ischemic stroke secondary to large vessel occlusion. We conducted an economic evaluation of these 2 therapeutic options.MethodsWe constructed a decision analytic model with a hypothetical cohort of 1000 patients to assess the cost-effectiveness of EVT with intravenous alteplase treatment versus EVT alone for acute ischemic stroke secondary to large vessel occlusion from both the societal and public health care payer perspectives. We used studies and data published in 2009-2021 for model inputs, and acquired cost data for Canada and China, representing high- and middle-income countries, respectively. We calculated incremental cost-effectiveness ratios (ICERs) using a lifetime horizon and accounted for uncertainty using 1-way and probabilistic sensitivity analyses. All costs are reported in 2021 Canadian dollars.ResultsIn Canada, the difference in quality-adjusted life-years (QALYs) gained between EVT with alteplase and EVT alone was 0.10 from both the societal and health care payer perspectives. The difference in cost was $2847 from a societal perspective and $2767 from the payer perspective. In China, the difference in QALYs gained was 0.07 from both perspectives, and the difference in cost was $1550 from the societal perspective and $1607 from the payer perspective. One-way sensitivity analyses showed that the distributions of modified Rankin Scale scores at 90 days after stroke were the most influential factor on ICERs. For Canada, compared to EVT alone, the probability that EVT with alteplase would be cost-effective at a willingness-to-pay threshold of $50 000 per QALY gained was 58.7% from a societal perspective and 58.4% from a payer perspective. The corresponding values for at a willingness-to-pay threshold of $47 185 (3 times the Chinese gross domestic product per capita in 2021) were 65.2% and 67.4%.InterpretationFor patients with acute ischemic stroke due to large vessel occlusion eligible for immediate treatment with both EVT alone and EVT with intravenous alteplase treatment, it is uncertain whether EVT with alteplase is cost-effective compared to EVT alone in Canada and China.

Project description:ImportanceIntravenous thrombolysis (IVT) followed by mechanical thrombectomy (MT) is recommended to treat acute ischemic stroke (AIS) with a large vessel occlusion (LVO). Most hospitals do not have on-site MT facilities, and most patients need to be transferred secondarily after IVT (drip and ship), which may have an effect on the neurologic outcome.ObjectiveTo compare the functional independence at 3 months between patients treated under the drip-and-ship paradigm and those treated on site (mothership).Design, setting, and participantsThis study used a prospectively gathered registry of patients with AIS to select patients admitted through the Saint-Antoine and Tenon (drip and ship) or the Fondation Rothschild (mothership) hospitals from January 1, 2013, through April 30, 2016. The study included patients older than 18 years treated with bridging therapy for AIS with LVO of the anterior circulation. Among the 159 patients who received MT at the mothership, 100 had been transferred after IVT from the drip-and-ship hospitals and 59 had received IVT on site.Main outcomes and measuresThe main outcome was 3-month functional independence (modified Rankin scale score ≤2). Both groups were compared using a multivariate linear model, including variables that were significantly different in the 2 groups.ResultsDuring the study period, 497 patients were hospitalized at the drip-and-ship and mothership hospitals for an AIS eligible to reperfusion therapy; 11 patients had a basilar artery occlusion and were excluded, leaving 100 patients in the drip-and-ship group (mean age, 73 years; age range, 60-81 years; 57 men [57.0%]) and 59 in the mothership group (mean age, 70 years; age range, 58-82 years; 29 men [49.2%]). The proportion of patients with a favorable neurologic outcome at 3 months was similar in both groups (drip and ship, 61 [61.0%]; mothership, 30 [50.8%]; P = .26), even after adjusting the analysis for the baseline National Institutes of Health Stroke Scale score, diffusion-weighted imaging Alberta Stroke Program Early Computed Tomography Score, and general anesthesia (P = .82). Patients had less severe conditions in the drip-and-ship group (median baseline National Institutes of Health Stroke Scale score, 15 vs 17 [P = .03]; median diffusion-weighted imaging Alberta Stroke Program Early Computed Tomography Score, 7.5 vs 7 [P = .05]). Process times were longer in the drip-and-ship group (onset-to-needle time, 150 vs 135 minutes; onset-to-puncture time, 248 vs 189 minutes; and onset-to-recanalization time, 297 vs 240 minutes; P < .001). Both groups were similar in terms of substantial recanalization (Thrombolysis in Cerebral Ischemia scores 2B to 3; drip and ship, 84 [84.0%]; mothership, 47 [79.7%]; P = .49) and symptomatic hemorrhagic transformation (drip and ship, 2 [2.0%]; mothership, 2 [3.4%]; P = .63).Conclusions and relevanceThis study found that patients treated under the drip-and-ship paradigm also benefit from bridging therapy, with no statistically significant difference compared with those treated directly in a comprehensive stroke center.

Project description:ImportanceRandomized clinical trials have demonstrated the efficacy and safety of endovascular thrombectomy for acute ischemic stroke with large infarct. Patients older than 80 years with large infarct are commonly encountered in clinical practice but underrepresented in randomized clinical trials.ObjectiveTo provide an age-based analysis of functional outcomes in endovascular thrombectomy for acute ischemic strokes with large infarct.Design, setting, and participantsThis retrospective multicenter cohort study included patients from the German Stroke Registry who received endovascular thrombectomy for acute ischemic stroke with large infarct at 1 of 25 German stroke centers between May 2015 and December 2021. Patients with acute ischemic stroke due to anterior circulation large vessel occlusion and large infarct were included. Large infarct was defined as an Alberta Stroke Program Early Computed Tomography Score of 0 to 5. Patients were subdivided by age to evaluate its association with functional outcomes.ExposureAge.Main outcomes and measuresPrimary outcomes were independent ambulation (90-day modified Rankin Scale score of 0-3) and mortality (90-day modified Rankin Scale score of 6).ResultsA total of 408 patients with large infarct were included (217 women [53.2%]; median [IQR] age, 75 [64-83] years). The rate of independent ambulation decreased from 56.4% in patients aged 60 years and younger (44 of 78 patients) to 15.1% in patients older than 80 years (19 of 126 patients) (P < .001), while mortality increased from 15.4% (12 patients) to 64.3% (81 patients) (P < .001). Being older than 80 years was associated with lower rates of independent ambulation (adjusted odds ratio [aOR], 0.44; 95% CI, 0.23-0.82; P = .01) and higher mortality (aOR, 2.75; 95% CI, 1.61-4.72; P < .001). A final modified Thrombolysis in Cerebral Infarction grade of 2b or 3 was associated with higher rates of independent ambulation (aOR, 4.95; 95% CI, 2.14-11.43; P < .001), independent of age and without significant interaction (aOR, 0.69; 95% CI, 0.35-1.34; P = .27).Conclusions and relevanceIn this cohort study of patients with acute ischemic stroke and large infarct, age was associated with functional outcomes. Patients older than 80 years had poor prognosis with high mortality but with sizeable differences depending on additional baseline and treatment characteristics. While it does not seem justified to apply a fixed upper age limit for endovascular thrombectomy, these results could assist clinicians in making informed treatment decisions in older patients with large ischemic stroke.

Dataset Information

Mass Spectrometry-Based Proteomic Profiling of Thrombotic Material Obtained by Endovascular Thrombectomy in Patients with Ischemic Stroke.

Publications

Mass Spectrometry-Based Proteomic Profiling of Thrombotic Material Obtained by Endovascular Thrombectomy in Patients with Ischemic Stroke.

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