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  • 1
    In: JAMA Neurology, American Medical Association (AMA), Vol. 80, No. 3 ( 2023-03-01), p. 233-
    Abstract: International guidelines recommend avoiding intravenous thrombolysis (IVT) in patients with ischemic stroke who have a recent intake of a direct oral anticoagulant (DOAC). Objective To determine the risk of symptomatic intracranial hemorrhage (sICH) associated with use of IVT in patients with recent DOAC ingestion. Design, Setting, and Participants This international, multicenter, retrospective cohort study included 64 primary and comprehensive stroke centers across Europe, Asia, Australia, and New Zealand. Consecutive adult patients with ischemic stroke who received IVT (both with and without thrombectomy) were included. Patients whose last known DOAC ingestion was more than 48 hours before stroke onset were excluded. A total of 832 patients with recent DOAC use were compared with 32 375 controls without recent DOAC use. Data were collected from January 2008 to December 2021. Exposures Prior DOAC therapy (confirmed last ingestion within 48 hours prior to IVT) compared with no prior oral anticoagulation. Main Outcomes and Measures The main outcome was sICH within 36 hours after IVT, defined as worsening of at least 4 points on the National Institutes of Health Stroke Scale and attributed to radiologically evident intracranial hemorrhage. Outcomes were compared according to different selection strategies (DOAC-level measurements, DOAC reversal treatment, IVT with neither DOAC-level measurement nor idarucizumab). The association of sICH with DOAC plasma levels and very recent ingestions was explored in sensitivity analyses. Results Of 33 207 included patients, 14 458 (43.5%) were female, and the median (IQR) age was 73 (62-80) years. The median (IQR) National Institutes of Health Stroke Scale score was 9 (5-16). Of the 832 patients taking DOAC, 252 (30.3%) received DOAC reversal before IVT (all idarucizumab), 225 (27.0%) had DOAC-level measurements, and 355 (42.7%) received IVT without measuring DOAC plasma levels or reversal treatment. The unadjusted rate of sICH was 2.5% (95% CI, 1.6-3.8) in patients taking DOACs compared with 4.1% (95% CI, 3.9-4.4) in control patients using no anticoagulants. Recent DOAC ingestion was associated with lower odds of sICH after IVT compared with no anticoagulation (adjusted odds ratio, 0.57; 95% CI, 0.36-0.92). This finding was consistent among the different selection strategies and in sensitivity analyses of patients with detectable plasma levels or very recent ingestion. Conclusions and Relevance In this study, there was insufficient evidence of excess harm associated with off-label IVT in selected patients after ischemic stroke with recent DOAC ingestion.
    Type of Medium: Online Resource
    ISSN: 2168-6149
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
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  • 2
    In: Journal of Neuroimaging, Wiley, Vol. 32, No. 6 ( 2022-11), p. 1134-1141
    Abstract: To investigate the association of different phenotypes, count, and locations of chronic covert brain infarctions (CBI) with long‐term mortality in patients with first‐ever manifest acute ischemic stroke (AIS) or transient ischemic attack (TIA). Additionally, to analyze their potential interaction with white matter hyperintensities (WMH) and predictive value in addition to established mortality scores. Methods Single‐center cohort study including consecutive patients with first‐ever AIS or TIA with available MRI imaging from January 2015 to December 2017. Blinded raters adjudicated CBI phenotypes and WMH (age‐related white matter changes score) according to established definitions. We compared Cox regression models including prespecified established predictors of mortality using Harrell's C and likelihood ratio tests. Results A total of 2236 patients (median [interquartile range] age: 71 [59‐80] years, 43% female, National Institutes of Health Stroke Scale: 2 [1‐6], median follow‐up: 1436 days, 21% death during follow‐up) were included. Increasing WMH (per point adjusted Hazard Ratio [aHR]  = 1.29 [1.14‐1.45]), but not CBI (aHR = 1.21 [0.99‐1.49] ), were independently associated with mortality. Neither CBI phenotype, count, nor location was associated with mortality and there was no multiplicative interaction between CBI and WMH ( p   〉  .1). As compared to patients without CBI or WMH, patients with moderate or severe WMH and additional CBI had the highest hazards of death (aHR = 1.62 [1.23‐2.13]). The Cox regression model including CBI and WMH had a small but significant increment in Harrell's C when compared to the model including 14 clinical variables (0.831 vs. 0.827, p   〈  .001). Discussion WMH represent a strong surrogate biomarker of long‐term mortality in first‐ever manifest AIS or TIA patients. CBI phenotypes, count, and location seem less relevant. Incorporation of CBI and WMH slightly improves predictive capacity of established risk scores.
    Type of Medium: Online Resource
    ISSN: 1051-2284 , 1552-6569
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2035400-9
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  • 3
    In: Journal of NeuroInterventional Surgery, BMJ
    Abstract: A potential benefit of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) is pre-interventional reperfusion. Currently, there are few data on the occurrence of pre-interventional reperfusion in patients randomized to IVT or no IVT before MT. Methods SWIFT DIRECT (Solitaire With the Intention For Thrombectomy Plus Intravenous t-PA vs DIRECT Solitaire Stent-retriever Thrombectomy in Acute Anterior Circulation Stroke) was a randomized controlled trial including acute ischemic stroke IVT eligible patients being directly admitted to a comprehensive stroke center, with allocation to IVT with MT versus MT alone. The primary endpoint of this analysis was the occurrence of pre-interventional reperfusion, defined as a pre-interventional expanded Thrombolysis in Cerebral Infarction score of ≥2a. The effect of IVT and potential treatment effect heterogeneity were analyzed using logistic regression analyses. Results Of 396 patients, pre-interventional reperfusion occurred in 20 (10.0%) patients randomized to IVT with MT, and in 7 (3.6%) patients randomized to MT alone. Receiving IVT favored the occurrence of pre-interventional reperfusion (adjusted OR 2.91, 95% CI 1.23 to 6.87). There was no IVT treatment effect heterogeneity on the occurrence of pre-interventional reperfusion with different strata of Randomization-to-Groin-Puncture time (p for interaction=0.33), although the effect tended to be stronger in patients with a Randomization-to-Groin-Puncture time 〉 28 min (adjusted OR 4.65, 95% CI 1.16 to 18.68). There were no significant differences in rates of functional outcomes between patients with and without pre-interventional reperfusion. Conclusion Even for patients with proximal large vessel occlusions and direct access to MT, IVT resulted in an absolute increase of 6% in rates of pre-interventional reperfusion. The influence of time strata on the occurrence of pre-interventional reperfusion should be studied further in an individual patient data meta-analysis of comparable trials. Trial registration number clinicaltrials.gov NCT03192332 .
    Type of Medium: Online Resource
    ISSN: 1759-8478 , 1759-8486
    Language: English
    Publisher: BMJ
    Publication Date: 2022
    detail.hit.zdb_id: 2506028-4
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  • 4
    In: Clinical Neuroradiology, Springer Science and Business Media LLC
    Abstract: Data on long-term effect of mechanical thrombectomy (MT) in patients with large ischemic cores (≥ 70 ml) are scarce. Our study aimed to assess the long-term outcomes in MT-patients according to baseline advanced imaging parameters. Methods We performed a single-centre retrospective cohort study of stroke patients receiving MT between January 1, 2010 and December 31, 2018. We assessed baseline imaging to determine core and mismatch volumes and hypoperfusion intensity ratio (with low ratio reflecting good collateral status) using RAPID automated post-processing software. Main outcomes were cross-sectional long-term mortality, functional outcome and quality of life by May 2020. Analysis were stratified by the final reperfusion status. Results In total 519 patients were included of whom 288 (55.5%) have deceased at follow-up (median follow-up time 28 months, interquartile range 1–55). Successful reperfusion was associated with lower long-term mortality in patients with ischemic core volumes ≥ 70 ml (adjusted hazard ratio (aHR) 0.20; 95% confidence interval (95% CI) 0.10–0.44) and ≥ 100 ml (aHR 0.26; 95% CI 0.08–0.87). The effect of successful reperfusion on long-term mortality was significant only in the presence of relevant mismatch (aHR 0.17; 95% CI 0.01–0.44). Increasing reperfusion grade was associated with a higher rate of favorable outcomes (mRS 0–3) also in patients with ischemic core volume ≥ 70 ml (aOR 3.58, 95% CI 1.64–7.83). Conclusion Our study demonstrated a sustainable benefit of better reperfusion status in patients with large ischemic core volumes. Our results suggest that patient deselection based on large ischemic cores alone is not advisable.
    Type of Medium: Online Resource
    ISSN: 1869-1439 , 1869-1447
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2232347-8
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  • 5
    In: Stroke: Vascular and Interventional Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 3, No. S2 ( 2023-11)
    Abstract: Clinical utility and diagnostic sensitivity of new‐generation flat‐panel computed tomography perfusion imaging (FPCTP) performed immediately after mechanical thrombectomy (MT) is unknown. We aimed to assess whether FPCTP obtained directly after MT could provide additional potentially relevant information on tissue reperfusion status. Methods Qualitative, single‐center analysis of all consecutive acute stroke patients admitted between 06/2019 and 03/2021 who underwent MT and post‐interventional FPCTP (n=26). A core‐lab blinded to technical details and clinical data performed reperfusion grading on post‐interventional digital subtraction angiography (DSA) images and time‐sensitive FPCTP maps. All patients were classified according to agreement between DSA and FPCTP. Results In 10/26 patients FPCTP revealed new, potentially clinically relevant information. Core‐lab adjudicated dichotomized detection of hypoperfusion (present/absent) was concurring in 21/26 (81%) patients. Of these, reperfusion findings showed perfect agreement on location and size in 16 (62%) patients, while in 5 (19%) patients with incomplete reperfusion, FPCTP showed additional hypoperfused areas missed on DSA. Of the remaining five patients subject to disagreement regarding the presence or absence of hypoperfusion, three showed complete reperfusion on DSA but hypoperfusion was noted on FPCTP, whereas two showed incomplete reperfusion on DSA without detectable hypoperfusion on FPCTP. FPCTP findings could have avoided Thrombolysis in Cerebral Infarction (TICI) overestimation in all false‐positive operator‐rated TICI3 cases. Conclusion In both core‐lab and real‐world operator assessment, FPCTP may provide additional clinically relevant information in a considerable percentage of patients undergoing MT. Hence, FPCTP may constitute a new standard for evaluating reperfusion efficacy and informed decision making in the angiography suite.
    Type of Medium: Online Resource
    ISSN: 2694-5746
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 3144224-9
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  • 6
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. Suppl_1 ( 2023-02)
    Abstract: Background: After successful reperfusion is achieved (extended Thrombolysis in Cerebral Infarction (eTICI) ≥2b50), decision on pursuing additional treatment strategies in order to achieve complete reperfusion (eTICI=2c/3), is multifactorial and depends on patient’s clinical and imaging characteristics. We have developed and validated a clinical decision tool to provide individualized predictions on achieving delayed reperfusion based on individual patient data. Methods: Single-center registry analysis for all consecutive patients admitted between 02/2015 - 12/2020. Primary variable of interest was perfusion imaging outcome in patients with incomplete reperfusion (eTICI 2a-2c), evaluated on the 24-hour follow-up imaging. This variable was dichotomized into delayed reperfusion, in case of non-observable perfusion deficit, and persistent perfusion deficit, in case of perfusion deficit captured on the final angiography imaging. Final model variable selection was performed via bootstrapped (n=200) stepwise backwards regression. Model was split into a training and testing set (80:20 ratio), with 10-fold cross validation resampling. Results: 372 patients (50.8% female, mean age 74) were included, with 228 (61.2%) of them having delayed reperfusion. Final model identified seven variables of importance including: age, sex, atrial fibrillation, Intervention-to-Follow-Up time, maneuver count, eTICI and collateral status. Model’s discriminative ability for predicting delayed reperfusion was adequate (AUC 0.83, 95% CI 0.74 -0.92), with an overall adjusted calibration (Brier score 0.17, 95% CI 0.15-0.18). Conclusions: Current model presents a tool that may aid clinical decision-making process in selection of patients for pursuing additional treatment strategies after incomplete reperfusion has been achieved. This is an important next step towards personalized treatment of stroke patients undergoing mechanical thrombectomy.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 1467823-8
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  • 7
    In: Stroke: Vascular and Interventional Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 1, No. S1 ( 2021-11)
    Abstract: Introduction : The value of intravenous thrombolysis (IVT) in patients eligible for mechanical thrombectomy (MT) remains unclear. We hypothesized that pre‐treatment with and/or ongoing IVT may facilitate reperfusion of distal vessel occlusion after incomplete MT. We evaluated this potential association using follow‐up perfusion imaging. Methods : Retrospective observational analysis of our institution`s stroke registry included patients with incomplete reperfusion after MT, admitted between February 1, 2015 and December 8, 2020. Delayed reperfusion (DR) was defined as the absence of a persistent perfusion deficit on contrast‐enhanced perfusion imaging ⁓24h±12h after the intervention. The association between baseline parameters and the occurrence of DR was evaluated using a logistic regression analyses. To account for possible time‐dependent associations of IVT with DR, additional stratification sets were made based on different time windows between IVT start time and final angiography runs. Results : Among the 378 included patients (median age 73.5, 50.8% female), DR occurred in 226 (59.8%). Atrial fibrillation (aOR 2.53 [95% CI 1.34 ‐ 4.90]), eTICI score (aOR 3.79 [95% CI 2.71 ‐ 5.48] per TICI grade increase), and intervention‐to‐follow‐up time (aOR 1.08 [95% CI 1.04 ‐ 1.13] per hour delay) were associated with DR. Dichotomized IVT strata showed no association with DR (aOR 0.75 [95% CI 0.42 ‐ 1.33] ), whereas shorter intervals between IVT start and end of the procedure showed a borderline significant association with DR (OR 2.24 [95% CI 0.98 ‐ 5.43, and OR 2.07 [95% 1.06 – 4.31], for 80 and 100 minutes respectively). Patients with DR had higher rates of functional independence (modified Rankin scale 0–2 at 90 days, DR: 63.3% vs PPD: 38.8%; p 〈 0.01) and longer survival time (at 3 years, DR: 69.2% vs PPD: 45.8%; p = 0.001). Conclusions : There is weak evidence that IVT may favor DR after incomplete MT if the time interval between IVT administration and end of the procedure is short. In general, perfusion follow‐up imaging may constitute a suitable surrogate parameter for evaluating medical rescue strategies after incomplete MT, because a considerable proportion of patients do not experience DR, and there seems to be a close correlation with clinical outcomes.
    Type of Medium: Online Resource
    ISSN: 2694-5746
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 3144224-9
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  • 8
    In: Stroke: Vascular and Interventional Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 3, No. S1 ( 2023-03)
    Abstract: One potential benefit of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) is pre‐interventional reperfusion. Currently, there is a paucity of data regarding the occurrence of pre‐interventional reperfusion in patients randomized to IVT or no‐IVT before MT. Methods SWIFT DIRECT was a randomized controlled trial including acute ischemic stroke IVT‐eligible patients being directly admitted to a comprehensive stroke center, with allocation to either MT alone or IVT + MT. Primary endpoint of this analysis was the occurrence of pre‐interventional reperfusion defined as pre‐interventional expanded Thrombolysis in Cerebral Infarction score ≥ 2a. The effect of IVT and potential treatment effect heterogeneity were analyzed using logistic regression analyses. Results Out of the 396 patients analyzed, pre‐interventional reperfusion occurred in 20 (10.0%) of patients randomized to IVT+MT, and 7 (3.6%) of patients randomized to MT alone. Receiving IVT favored the occurrence of pre‐interventional reperfusion (aOR 2.91 [95% CI 1.23 – 6.87]). There was no IVT treatment effect heterogeneity on the occurrence of pre‐interventional reperfusion with different strata of Randomization‐to‐Groin‐Puncture (p for interaction = 0.33), although the effect tended to be stronger in patients with Randomization‐to‐Groin‐Puncture 〉 28 minutes (aOR 4.65 [95% CI 1.16 – 18.68]). There were no significant difference in rates of functional outcomes between patients with and without pre‐interventional reperfusion. Conclusions Even for patients with proximal large vessel occlusions and direct access to MT, IVT leads towards an absolute increase of 6.9% (95% CI 1.7‐12.2%) in the rates of pre‐interventional reperfusion. The effect of IVT tended to be more pronounced when Randomization‐to‐Groin‐Puncture intervals were longer, but this heterogeneity did not reach statistical significance.
    Type of Medium: Online Resource
    ISSN: 2694-5746
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 3144224-9
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  • 9
    In: European Stroke Journal, SAGE Publications, Vol. 8, No. 2 ( 2023-06), p. 456-466
    Abstract: The clinical course of patients with incomplete reperfusion after thrombectomy, defined as an expanded Thrombolysis in Cerebral Infarction (eTICI) score of 2a–2c, is heterogeneous. Patients showing delayed reperfusion (DR) have good clinical outcomes, almost comparable to patients with ad-hoc TICI3 reperfusion. We aimed to develop and internally validate a model that predicts DR occurrence in order to inform physicians about the likelihood of a benign natural disease progression. Patients and methods: Single-center registry analysis including all consecutive, study-eligible patients admitted between 02/2015 and 12/2021. Preliminary variable selection for the prediction of DR was performed using bootstrapped stepwise backward logistic regression. Interval validation was performed with bootstrapping and the final model was developed using a random forests classification algorithm. Model performance metrics are reported with discrimination, calibration, and clinical decision curves. Primary outcome was concordance statistics as a measure of goodness of fit for the occurrence of DR. Results: A total of 477 patients (48.8% female, mean age 74 years) were included, of whom 279 (58.5%) showed DR on 24 follow-up. The model’s discriminative ability for predicting DR was adequate (C-statistics 0.79 [95% CI: 0.72–0.85]). Variables with strongest association with DR were: atrial fibrillation (aOR 2.06 [95% CI: 1.23–3.49] ), Intervention-To-Follow-Up time (aOR 1.06 [95% CI: 1.03–1.10]), eTICI score (aOR 3.49 [95% CI: 2.64–4.73] ), and collateral status (aOR 1.33 [95% CI: 1.06–1.68]). At a risk threshold of R = 30%, use of the prediction model could potentially reduce the number of additional attempts in one out of four patients who will have spontaneous DR, without missing any patients who do not show spontaneous DR on follow-up. Conclusions: The model presented here shows fair predictive accuracy for estimating chances of DR after incomplete thrombectomy. This may inform treating physicians on the chances of a favorable natural disease progression if no further reperfusion attempts are made.
    Type of Medium: Online Resource
    ISSN: 2396-9873 , 2396-9881
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2023
    detail.hit.zdb_id: 2851287-X
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  • 10
    In: Journal of NeuroInterventional Surgery, BMJ
    Abstract: Immediate non-contrast post-interventional flat-panel detector CT (FPDCT) has been suggested as an imaging tool to assess complications after endovascular therapy (EVT). We systematically investigated a new imaging finding of focal hyperdensities correlating with remaining distal vessel occlusion after EVT. Methods A single-center retrospective analysis was conducted for all acute ischemic stroke patients admitted between July 2020 and December 2022 who underwent EVT and immediate post-interventional FPDCT. A blinded core lab performed reperfusion grading on post-interventional digital subtraction angiography (DSA) images and evaluated focal hyperdensities on FPDCT (here called the distal occlusion tracker (DOT) sign). DOT sign was defined as a tubular or punctiform, vessel confined, hyperdense signal within the initial occlusion target territory. We assessed sensitivity and specificity of the DOT sign when compared with DSA findings. Results The median age of the cohort (n=215) was 74 years (IQR 63–82) and 58.6% were male. The DOT sign was positive in half of the cohort (51%, 110/215). The DOT sign had high specificity (85%, 95% CI 72% to 93%), but only moderate sensitivity (63%, 95% CI 55% to 70%) for detection of residual vessel occlusions. In comparison to the core lab, operators overestimated complete reperfusion in a quarter of the entire cohort (25%, 53/215). In more than half of these cases (53%, 28/53) there was a positive DOT sign, which could have mitigated this overestimation. Conclusion The DOT sign appears to be a frequent finding on immediate post-interventional FPDCT. It correlates strongly with incomplete reperfusion and indicates residual distal vessel occlusions. In the future, it may be used to complement grading of reperfusion success and may help mitigating overestimation of reperfusion in the acute setting.
    Type of Medium: Online Resource
    ISSN: 1759-8478 , 1759-8486
    Language: English
    Publisher: BMJ
    Publication Date: 2024
    detail.hit.zdb_id: 2506028-4
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