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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 the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 11, No. 24 ( 2022-12-20)
    Abstract: This study was conducted to explore the association of different phenotypes, count, and location of chronic covert brain infarctions (CBIs) with detection of atrial fibrillation (AF) on prolonged post‐stroke cardiac rhythm monitoring (PCM). Methods and Results We conducted a cohort single‐center study of consecutive first‐ever ischemic stroke or transient ischemic attack patients undergoing PCM between January 2015 and December 2017. We blindly rated CBI phenotypes according to established definitions and white matter hyperintensities (WMHs) according to the age‐related white matter changes rating scale. We used (multiple) regression models to assess the association of the imaging biomarkers and incident AF on PCM. A total of 795 patients (median [interquartile range]) aged 69 (57–78) years, 41% women, median National Institutes of Health Stroke Scale score 2 (0–5), median PCM duration 14 (7–14) days, and AF detection in 61 patients (7.7%) were included. On univariate analysis, WMHs (per point odds ratio, 1.35 [95% CI, 1.03–1.78] ) but not CBIs (odds ratio, 0.90 [95% CI, 0.52–1.56]) were associated with AF detection. Neither CBI phenotype, count, nor location were associated with AF detection. After adjustment for age, hypertension, and stroke severity, neither increasing WMHs (per point adjusted odds ratio, 0.85 [95% CI, 0.60–1.20] ) nor CBIs (adjusted odds ratio, 0.60 [95% CI, 0.33–1.09] ) were independently associated with AF detection. Conclusions Although WMHs and CBIs represent surrogate biomarkers of vascular risk factors, neither WMHs nor CBIs, including their phenotypes, count, and location, were independently associated with AF detection on PCM. In patients with manifest ischemic stroke or transient ischemic attack, the presence of imaging biomarkers of chronic ischemic injury does not seem promising to further refine prediction tools for AF detection on PCM.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2653953-6
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  • 3
    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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  • 4
    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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  • 5
    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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  • 6
    In: Journal of NeuroInterventional Surgery, BMJ, Vol. 15, No. 3 ( 2023-03), p. 227-232
    Abstract: Most trials comparing endovascular treatment (EVT) alone versus intravenous thrombolysis with alteplase (IVT) + EVT in directly admitted patients with a stroke are non-inferiority trials. However, the margin based on the level of uncertainty regarding non-inferiority of the experimental treatment that clinicians are willing to accept to incorporate EVT alone into clinical practice remains unknown. Objective To characterize what experienced stroke clinicians would consider an acceptable level of uncertainty for hypothetical decisions on whether to administer IVT or not before EVT in patients admitted directly to EVT-capable centers. Methods A web-based, structured survey was distributed to a cross-section of 600 academic neurologists/neurointerventionalists. For this purpose, a response framework for a hypothetical trial comparing IVT+EVT (standard of care) with EVT alone (experimental arm) was designed. In this trial, a similar proportion of patients in each arm achieved functional independence at 90 days. Invited physicians were asked at what level of certainty they would feel comfortable skipping IVT in clinical practice, considering these hypothetical trial results. Results There were 180 respondents (response rate: 30%) and 165 with complete answers. The median chosen acceptable uncertainty suggesting reasonable comparability between both treatments was an absolute difference in the rate of day 90 functional independence of 3% (mode 5%, IQR 1–5%), with higher chosen margins observed in interventionalists (aOR 2.20, 95% CI 1.06 to 4.67). Conclusion Physicians would generally feel comfortable skipping IVT before EVT at different certainty thresholds. Most physicians would treat with EVT alone if randomized trial data suggested that the number of patients achieving functional independence at 90 days was similar between the two groups, and one could be sufficiently sure that no more than 3 out of 100 patients would not achieve functional independence at 90 days due to skipping IVT.
    Type of Medium: Online Resource
    ISSN: 1759-8478 , 1759-8486
    Language: English
    Publisher: BMJ
    Publication Date: 2023
    detail.hit.zdb_id: 2506028-4
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  • 7
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 14 ( 2023-9-28)
    Abstract: Paraneoplastic coagulopathy can present as stroke and is associated with specific biomarker changes. Identifying paraneoplastic coagulopathy can help guide secondary prevention in stroke patients, and early cancer detection might improve outcomes. However, unlike ischemic stroke, it remains unclear whether paraneoplastic coagulopathy is associated with transient ischemic attacks (TIA). This study assessed the presence of cancer-related biomarkers in TIA patients and evaluated long-term mortality rates in patients with and without active cancer. Methods Active cancer was retrospectively identified in consecutive TIA patients treated at a comprehensive stroke center between 2015 and 2019. An association between the presence of cancer and cancer-related biomarkers was assessed using multivariable logistic regression. Long-term mortality after TIA was analyzed using multivariable Cox regression. Results Among 1436 TIA patients, 72 had active cancer (5%), of which 17 were occult (1.2%). Cancer-related TIA was associated with male gender (adjusted odds ratio [aOR] 2.29, 95% CI 1.12–4.68), history of smoking (aOR 2.77, 95% CI 1.34–5.7), elevated D-dimer (aOR 1.77, 95% CI 1.26–2.49), lactate dehydrogenase (aOR 1.003, 95% CI 1.00–1.005), lower leukocyte count (aOR 1.20, 95% CI 1.04–1.38), and lower hemoglobin (aOR 1.02, 95% CI 1.00–1.04). Long-term mortality was associated with both active cancer (adjusted hazard ratios [aHR] 2.47, 95% CI 1.58–3.88) and occult cancer (aHR 3.08, 95% CI 1.30–7.32). Conclusion Cancer-related TIA is not uncommon. Biomarkers known to be associated with cancer-related stroke also seem to be present in TIA patients. Early identification would enable targeted treatment strategies and could improve outcomes in this patient population.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2564214-5
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  • 8
    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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  • 9
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. 7 ( 2023-07), p. 1708-1717
    Abstract: The optimal management of patients with isolated posterior cerebral artery occlusion is uncertain. We compared clinical outcomes for endovascular therapy (EVT) versus medical management (MM) in patients with isolated posterior cerebral artery occlusion. METHODS: This multinational case-control study conducted at 27 sites in Europe and North America included consecutive patients with isolated posterior cerebral artery occlusion presenting within 24 hours of time last well from January 2015 to August 2022. Patients treated with EVT or MM were compared with multivariable logistic regression and inverse probability of treatment weighting. The coprimary outcomes were the 90-day modified Rankin Scale ordinal shift and ≥2-point decrease in the National Institutes of Health Stroke Scale. RESULTS: Of 1023 patients, 589 (57.6%) were male with median (interquartile range) age of 74 (64–82) years. The median (interquartile range) National Institutes of Health Stroke Scale was 6 (3–10). The occlusion segments were P1 (41.2%), P2 (49.2%), and P3 (7.1%). Overall, intravenous thrombolysis was administered in 43% and EVT in 37%. There was no difference between the EVT and MM groups in the 90-day modified Rankin Scale shift (aOR, 1.13 [95% CI, 0.85–1.50]; P =0.41). There were higher odds of a decrease in the National Institutes of Health Stroke Scale by ≥2 points with EVT (aOR, 1.84 [95% CI, 1.35–2.52]; P =0.0001). Compared with MM, EVT was associated with a higher likelihood of excellent outcome (aOR, 1.50 [95% CI, 1.07–2.09]; P =0.018), complete vision recovery, and similar rates of functional independence (modified Rankin Scale score, 0–2), despite a higher rate of SICH and mortality (symptomatic intracranial hemorrhage, 6.2% versus 1.7%; P =0.0001; mortality, 10.1% versus 5.0%; P =0.002). CONCLUSIONS: In patients with isolated posterior cerebral artery occlusion, EVT was associated with similar odds of disability by ordinal modified Rankin Scale, higher odds of early National Institutes of Health stroke scale improvement, and complete vision recovery compared with MM. There was a higher likelihood of excellent outcome in the EVT group despite a higher rate of symptomatic intracranial hemorrhage and mortality. Continued enrollment into ongoing distal vessel occlusion randomized trials is warranted.
    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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  • 10
    In: European Stroke Journal, SAGE Publications
    Abstract: Covert brain infarction (CBI) is highly prevalent and linked with stroke risk factors, increased mortality, and morbidity. Evidence to guide management is sparse. We sought to gain information on current practice and attitudes toward CBI and to compare differences in management according to CBI phenotype. Methods: We conducted a web-based, structured, international survey from November 2021 to February 2022 among neurologists and neuroradiologists. The survey captured respondents’ baseline characteristics, general approach toward CBI and included two case scenarios designed to evaluate management decisions taken upon incidental detection of an embolic-phenotype and a small-vessel-disease phenotype. Results: Of 627 respondents (38% vascular neurologists, 24% general neurologists, and 26% neuroradiologists), 362 (58%) had a partial, and 305 (49%) a complete response. Most respondents were university hospital senior faculty members experienced in stroke, mostly from Europe and Asia. Only 66 (18%) of respondents had established institutional written protocols to manage CBI. The majority indicated that they were uncertain regarding useful investigations and further management of CBI patients (median 67 on a slider 0–100, 95% CI 35–81). Almost all respondents (97%) indicated that they would assess vascular risk factors. Although most would investigate and treat similarly to ischemic stroke for both phenotypes, including initiating antithrombotic treatment, there was considerable diagnostic and therapeutic heterogeneity. Less than half of respondents (42%) would assess cognitive function or depression. Conclusions: There is a high degree of uncertainty and heterogeneity regarding management of two common types of CBI, even among experienced stroke physicians. Respondents were more proactive regarding the diagnostic and therapeutic management than the minimum recommended by current expert opinions. More data are required to guide management of CBI; meantime, more consistent approaches to identification and consistent application of current knowledge, that also consider cognition and mood, would be promising first steps to improve consistency of care.
    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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