Mechanical Characterization of Thrombi Retrieved With Endovascular Thrombectomy in Patients With Acute Ischemic Stroke.
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ABSTRACT:
SUBMITTER: Boodt N
PROVIDER: S-EPMC8312567 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Mechanical thrombectomy is a novel treatment option for patients with acute ischemic stroke (AIS). Only a few studies have previously suggested strategies to categorize retrieved clots according to their histologic composition. However, these reports did not analyze potential biomarkers that are of importance in stroke-related inflammation. We therefore histopathologically investigated 37 intracerebral thrombi mechanically retrieved from patients with AIS, and focused on the composition of immune cells and platelets. We also conducted correlation analyses of distinctive morphologic patterns (erythrocytic, serpentine, layered, red, white, mixed appearance) with clinical parameters. Most T cells and monocytes were detected in erythrocytic and red clots, in which the distribution of these cells was random. In contrast, von Willebrand factor (vWF)-positive areas co-localized with regions of fibrin and collagen. While clots with huge amounts of vWF seem to be associated with a high National Institute of Health Stroke Scale score at admission, histologic findings could not predict the clinical outcome at discharge. In summary, we provide the first histologic description of mechanically retrieved intracerebral thrombi regarding biomarkers relevant for inflammation in ischemic stroke.
| S-EPMC4813162 | biostudies-literature
Project description:Mechanical thrombectomy (MT) is effective in managing patients with acute ischemic stroke (AIS) caused by large-vessel occlusions and allows for valuable histological analysis of thrombi. However, whether bridging therapy (pretreatment with intravenous thrombolysis before MT) provides additional benefits in patients with middle cerebral artery (MCA) occlusion remains unclear. Therefore, this study aimed to compare the effects of direct MT and bridging therapy, and to elucidate the correlation between thrombus composition and stroke subtypes. Seventy-three patients with acute ischemic stroke who received MT, were eligible for intravenous thrombolysis, and had MCA occlusion were included. We matched 21 direct MT patients with 21 bridging therapy patients using propensity score matching and compared their 3rd-month clinical outcomes. All MCA thrombi (n = 45) were histologically analyzed, and the red blood cell (RBC) and fibrin percentages were quantified. We compared the clot composition according to stroke etiology (large-artery atherosclerosis and cardioembolism) and intravenous thrombolysis application. The baseline characteristics showed no difference between groups except for a higher atrial fibrillation rate and NIHSS score on admission in the direct MT group. We performed a supportive analysis using propensity score matching but could not find any differences in the functional outcome, mortality, and intracerebral hemorrhage. In the histological clot analysis, the cardioembolic clots without intravenous thrombolysis pretreatment had higher RBC (P = 0.042) and lower fibrin (P = 0.042) percentages than the large-artery atherosclerosis thrombi. Similar findings were observed in the thrombi treated with recombinant tissue plasminogen activator (P = 0.012). In conclusion, there was no difference in the functional outcomes between the direct MT and bridging therapy groups. However, randomized trials are needed to elucidate the high ratio of cardioembolism subtype in our group of patients. The histological MCA thrombus composition differed between cardioembolism and large-artery atherosclerosis, and this finding provides valuable information on the underlying pathogenesis and thrombus origin.
| S-EPMC6686432 | biostudies-literature
Project description: Not available
| S-EPMC10569475 | biostudies-literature
Project description:The development of the endovascular thrombectomy (EVT) technique has revolutionized acute stroke management for patients with large vessel occlusions (LVOs). The impact of successful recanalization using an EVT on autoregulatory profiles is unknown. A more complete understanding of cerebral autoregulation in the context of EVT may assist with post-procedure hemodynamic optimization to prevent complications. We examined cerebral autoregulation in 107 patients with an LVO in the anterior circulation (proximal middle cerebral artery (M1/2) and internal cerebral artery (ICA) terminus) who had been treated using an EVT. Dynamic cerebral autoregulation was assessed at multiple time points, ranging from less than 24 hours to 5 days following last seen well (LSW) time, using transcranial Doppler ultrasound recordings and transfer function analysis. Complete (Thrombolysis in Cerebral Infarction (TICI) 3) recanalization was associated with a more favorable autoregulation profile compared with TICI 2b or poorer recanalization (p < 0.05), which is an effect that was present after accounting for differences in the infarct volumes. Less effective autoregulation in the first 24 h following the LSW time was associated with increased rates of parenchymal hematoma types 1 and 2 hemorrhagic transformations (PH1-PH2). These data suggest that patients with incomplete recanalization and poor autoregulation (especially within the first 24 h post-LSW time) may warrant closer blood pressure monitoring and control in the first few days post ictus.
| S-EPMC7564150 | biostudies-literature
Project description:BackgroundRandomized controlled trials (RCTs) have compared mechanical endovascular therapy (MET) in addition to intravenous tissue plasminogen activator (IVtPA) to IVtPA alone for the management of acute ischemic stroke (AIS). Direct comparative studies between individual METs are not available. In lieu of head-to-head randomized control trials, we performed an adjusted indirect treatment comparison (ITC) meta-analysis to assess the comparative efficacy and safety of different METs, Solitaire+IVtPA and Penumbra+IVtPA in AIS patients.Methods and findingsWe searched MEDLINE, the Cochrane Central Register of Controlled Trials and Embase from January 1, 2005 through April 1, 2017 for RCTs in AIS patients, comparing a single MET+IVtPA to IVtPA alone and reporting shift in ordinal modified Rankin Scale (mRS) score at 90 days. Secondary endpoints included 90 day mortality and symptomatic intracranial hemorrhage (sICH). Endpoints were pooled using traditional random effects meta-analysis methods, producing odds ratios and 95% confidence intervals. Adjusted ITCs using pooled estimates were then performed. Three studies (SWIFT PRIME, EXTEND-IA, THERAPY) were included; two evaluating the Solitaire stent retriever and one the Penumbra system. Traditional meta-analysis demonstrated that each MET+IVtPA resulted in increased odds of improving ordinal mRS score vs. IVtPA alone, but did not alter the odds of death or sICH. Adjusted ITC showed no significant difference between the METs for any outcome.ConclusionNo significant difference in efficacy or safety between the Solitaire and Penumbra devices was observed.
| S-EPMC5841644 | biostudies-literature
Project description:BackgroundThe beneficial effects of endovascular treatment with new-generation mechanical thrombectomy devices compared with intravenous thrombolysis alone to treat acute large-artery ischemic stroke have been shown in randomized controlled trials (RCTs). This study aimed to estimate the cost utility of mechanical thrombectomy compared with the established standard of care.MethodsWe developed a Markov decision process analytic model to assess the cost-effectiveness of treatment with mechanical thrombectomy plus intravenous thrombolysis versus treatment with intravenous thrombolysis alone from the public payer perspective in Canada. We conducted comprehensive literature searches to populate model inputs. We estimated the efficacy of mechanical thrombectomy plus intravenous thrombolysis from a meta-analysis of 5 RCTs, and we used data from the Oxford Vascular Study to model long-term clinical outcomes. We calculated incremental cost-effectiveness ratios (ICER) using a 5-year time horizon.ResultsThe base case analysis showed the cost and effectiveness of treatment with mechanical thrombectomy plus intravenous thrombolysis to be $126?939 and 1.484 quality-adjusted life-years (QALYs), respectively, and the cost and effectiveness of treatment with intravenous thrombolysis alone to be $124?419 and 1.273 QALYs, respectively. The mechanical thrombectomy plus intravenous thrombolysis strategy was associated with an ICER of $11?990 per QALY gained. Probabilistic sensitivity analysis showed that the probability of treatment with mechanical thrombectomy plus intravenous thrombolysis being cost-effective was 57.5%, 89.7% and 99.6% at thresholds of $20?000, $50?000 and $100?000 per QALY gained, respectively. The main factors influencing the ICER were time horizon, extra cost of mechanical thrombectomy treatment and age of the patient.InterpretationMechanical thrombectomy as an adjunct therapy to intravenous thrombolysis is cost-effective compared with treatment with intravenous thrombolysis alone for patients with acute large-artery ischemic stroke.
| S-EPMC4933608 | biostudies-literature
Project description:PurposeIntravenous thrombolysis and mechanical thrombectomy (MT) are standard of care in patients with acute ischemic stroke due to large vessel occlusion. Data on MT in patients with intracranial hemorrhage prior to intervention is limited to anecdotal reports, as these patients were excluded from thrombectomy trials.MethodsWe analyzed patients from an observational multicenter cohort with acute ischemic stroke and endovascular treatment, the German Stroke Registry-Endovascular Treatment trial, with intracranial hemorrhage before MT. Baseline characteristics, procedural parameters and functional outcome at 90 days were analyzed and compared to a propensity score matched cohort.ResultsOut of 6635 patients, we identified 32 patients (0.5%) with acute ischemic stroke due to large vessel occlusion and preinterventional intracranial hemorrhage who underwent MT. Risk factors of intracranial hemorrhage were head trauma, oral anticoagulation and intravenous thrombolysis. Overall mortality was high (50%) but among patients with a premorbid modified Rankin scale (mRS) of 0-2 (n = 15), good clinical outcome (mRS 0-2) at 90 days was achieved in 40% of patients. Periprocedural and outcome results did not differ between patients with and without preinterventional intracranial hemorrhage.ConclusionPreinterventional intracranial hemorrhage in acute ischemic stroke patients with large vessel occlusion is rare. The use of MT is technically feasible and a substantial number of patients achieve good clinical outcome, indicating that MT should not be withheld in patients with preinterventional intracranial hemorrhage.
| S-EPMC9424164 | biostudies-literature
Project description:Although intravenous thrombolysis increases the probability of a good functional outcome in carefully selected patients with acute ischemic stroke, a substantial proportion of patients who receive thrombolysis do not have a good outcome. Several recent trials of mechanical thrombectomy appear to indicate that this treatment may be superior to thrombolysis. We therefore conducted a systematic review and meta-analysis to evaluate the clinical effectiveness and safety of new-generation mechanical thrombectomy devices with intravenous thrombolysis (if eligible) compared with intravenous thrombolysis (if eligible) in patients with acute ischemic stroke caused by a proximal intracranial occlusion. We systematically searched seven databases for randomized controlled trials published between January 2005 and March 2015 comparing stent retrievers or thromboaspiration devices with best medical therapy (with or without intravenous thrombolysis) in adults with acute ischemic stroke. We assessed risk of bias and overall quality of the included trials. We combined the data using a fixed or random effects meta-analysis, where appropriate. We identified 1579 studies; of these, we evaluated 122 full-text papers and included five randomized control trials (n=1287). Compared with patients treated medically, patients who received mechanical thrombectomy were more likely to be functionally independent as measured by a modified Rankin score of 0-2 (odds ratio, 2.39; 95% confidence interval, 1.88-3.04; I2=0%). This finding was robust to subgroup analysis. Mortality and symptomatic intracerebral hemorrhage were not significantly different between the two groups. Mechanical thrombectomy significantly improves functional independence in appropriately selected patients with acute ischemic stroke.
| S-EPMC4926268 | biostudies-literature
Project description:Introduction: Endovascular thrombectomy (EVT) increases the chance of good functional outcome after ischemic stroke caused by a large vessel occlusion, but the risk of death in the first 90 days is still considerable. We assessed the causes, timing and risk factors of death after EVT to aid future studies aiming to reduce mortality. Patients and methods: We used data from the MR CLEAN Registry, a prospective, multicenter, observational cohort study of patients treated with EVT in the Netherlands between March 2014, and November 2017. We assessed causes and timing of death and risk factors for death in the first 90 days after treatment. Causes and timing of death were determined by reviewing serious adverse event forms, discharge letters, or other written clinical information. Risk factors for death were determined with multivariable logistic regression. Results: Of 3180 patients treated with EVT, 863 (27.1%) died in the first 90 days. The most common causes of death were pneumonia (215 patients, 26.2%), intracranial hemorrhage (142 patients, 17.3%), withdrawal of life-sustaining treatment because of the initial stroke (110 patients, 13.4%) and space-occupying edema (101 patients, 12.3%). In total, 448 patients (52% of all deaths) died in the first week, with intracranial hemorrhage as most frequent cause. The strongest risk factors for death were hyperglycemia and functional dependency before the stroke and severe neurological deficit at 24–48 h after treatment. Discussion and conclusion: When EVT fails to decrease the initial neurological deficit, strategies to prevent complications like pneumonia and intracranial hemorrhage after EVT could improve survival, as these are often the cause of death.
| S-EPMC10069200 | biostudies-literature
Project description:BackgroundDetermining stroke etiology is crucial for secondary prevention, but intensive workups fail to classify ~30% of strokes that are cryptogenic.ObjectiveTo examine the hypothesis that the transcriptomic profiles of clots retrieved during mechanical thrombectomy are unique to strokes of different subtypes.MethodsWe isolated RNA from the clots of 73 patients undergoing mechanical thrombectomy. Samples of sufficient quality were subjected to 100-cycle, paired-end RNAseq, and transcriptomes with less than 10 million unique reads were excluded from analysis. Significant differentially expressed genes (DEGs) between subtypes (defined by the Trial of Org 10 172 in Acute Stroke Treatment) were identified by expression analysis in edgeR. Gene ontology enrichment analysis was used to study the biologic differences between stroke etiologies.ResultsIn all, 38 clot transcriptomes were analyzed; 6 from large artery atherosclerosis (LAA), 21 from cardioembolism (CE), 5 from strokes of other determined origin, and 6 from cryptogenic strokes. Among all comparisons, there were 816 unique DEGs, 174 of which were shared by at least two comparisons, and 20 of which were shared by all three. Gene ontology analysis showed that CE clots reflected high levels of inflammation, LAA clots had greater oxidoreduction and T-cell processes, and clots of other determined origin were enriched for aberrant platelet and hemoglobin-related processes. Principal component analysis indicated separation between these subtypes and showed cryptogenic samples clustered among several different groups.ConclusionsExpression profiles of stroke clots were identified between stroke etiologies and reflected different biologic responses. Cryptogenic thrombi may be related to multiple etiologies.
| S-EPMC9789205 | biostudies-literature