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  • 1
    In: Nature Human Behaviour, Springer Science and Business Media LLC, Vol. 7, No. 4 ( 2023-02-09), p. 484-501
    Type of Medium: Online Resource
    ISSN: 2397-3374
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2885046-4
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  • 2
    In: International Journal of Stroke, SAGE Publications, Vol. 10, No. 4 ( 2015-06), p. 534-540
    Abstract: Atrial fibrillation is associated with greater baseline neurological impairment and worse outcomes following ischemic stroke. Previous studies suggest that greater volumes of more severe baseline hypoperfusion in patients with history of atrial fibrillation may explain this association. We further investigated this association by comparing patients with and without atrial fibrillation on initial examination following stroke using pooled multimodal magnetic resonance imaging and clinical data from the Echoplanar Imaging Thrombolytic Evaluation Trial and the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution studies. Methods Echoplanar Imaging Thrombolytic Evaluation Trial was a trial of 101 ischemic stroke patients randomized to intravenous tissue plasminogen activator or placebo, and Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution was a prospective cohort of 74 ischemic stroke patients treated with intravenous tissue plasminogen activator at three to six hours following symptom onset. Patients underwent multimodal magnetic resonance imaging before treatment, at three to five days and three-months after stroke in Echoplanar Imaging Thrombolytic Evaluation Trial; before treatment, three to six hours after treatment and one-month after stroke in Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution. Patients were assessed with the National Institutes of Health Stroke Scale and the modified Rankin scale before treatment and at three-months after stroke. Patients were categorized into definite atrial fibrillation (present on initial examination), probable atrial fibrillation (history but no atrial fibrillation on initial examination), and no atrial fibrillation. Perfusion data were reprocessed with automated magnetic resonance imaging analysis software (RAPID, Stanford University, Stanford, CA, USA). Hypoperfusion volumes were defined using time to maximum delays in two-second increments from 〈 4 to 〉 8 s. Hemorrhagic transformation was classified according to the European Cooperative Acute Stroke Studies criteria. Results Of the 175 patients, 28 had definite atrial fibrillation, 30 probable atrial fibrillation, 111 no atrial fibrillation, and six were excluded due to insufficient imaging data. At baseline, patients with definite atrial fibrillation had more severe hypoperfusion (median time to maximum 〉 8 s, volume 48 vs. 29 ml, P = 0·02) compared with patients with no atrial fibrillation. At outcome, patients with definite atrial fibrillation had greater infarct growth (median volume 47 vs. 8 ml, P = 0·001), larger infarcts (median volume 75 vs. 23 ml, P = 0·001), more frequent parenchymal hematoma grade hemorrhagic transformation (30% vs. 10%, P = 0·03), worse functional outcomes (median modified Rankin scale score 4 vs. 3, P = 0·03), and higher mortality (36% vs. 16%, P = 0·03) compared with patients with no atrial fibrillation. Definite atrial fibrillation was independently associated with increased parenchymal hematoma (odds ratio = 6·05, 95% confidence interval 1·60–22·83) but not poor functional outcome (modified Rankin scale 3–6, odds ratio = 0·99, 95% confidence interval 0·35–2·80) or mortality (odds ratio = 2·54, 95% confidence interval 0·86–7·49) three-months following stroke, after adjusting for other baseline imbalances. Conclusion Atrial fibrillation is associated with greater volumes of more severe baseline hypoperfusion, leading to higher infarct growth, more frequent severe hemorrhagic transformation and worse stroke outcomes.
    Type of Medium: Online Resource
    ISSN: 1747-4930 , 1747-4949
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2015
    detail.hit.zdb_id: 2211666-7
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  • 3
    In: International Journal of Stroke, SAGE Publications, Vol. 9, No. 2 ( 2014-02), p. 156-159
    Abstract: Reperfusion is associated with good functional outcome after stroke. However, minimal data are available regarding the effect of reperfusion on clinical outcome and infarct growth in patients with distal MCA branch occlusions. Aim The aim of this study was to evaluate this association and to determine the impact of the perfusion-diffusion mismatch. Methods Individual patient data from three stroke studies (EPITHET, DEFUSE and DEFUSE 2) with baseline MRI profiles and reperfusion status were pooled. Patients were included if they had a single cortical perfusion lesion on their baseline MRI that was consistent with a distal MCA branch occlusion. Good functional outcome was defined as a score of 0–2 on the modified Rankin Scale at day 90 and infarct growth was defined as change in lesion volume between the baseline DWI and the final T2/FLAIR. Results Thirty patients met inclusion criteria. Eighteen (60%) had a good functional outcome and twenty (67%) had reperfusion. Reperfusion was not associated with good functional outcome in the overall cohort (OR: 1·0, 95% CI 0·2–4·7) and also not in the subset of patients with a PWI-DWI mismatch ( n = 17; OR: 0·7, 95% CI 0·1–5·5). Median infarct growth was modest and not significantly different between patients with (0 ml) and without reperfusion (6 ml); P = 0·2. Conclusion The overall high rate of good outcomes in patients with distal MCA perfusion lesions might obscure a potential benefit from reperfusion in this population. A larger pooled analysis evaluating the effect of reperfusion in patients with distal MCA branch occlusions is warranted as confirmation of our results could have implications for the design of future stroke trials.
    Type of Medium: Online Resource
    ISSN: 1747-4930 , 1747-4949
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2014
    detail.hit.zdb_id: 2211666-7
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  • 4
    In: Journal of Clinical Neuroscience, Elsevier BV, Vol. 17, No. 12 ( 2010-12), p. 1630-
    Type of Medium: Online Resource
    ISSN: 0967-5868
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2010
    detail.hit.zdb_id: 2009190-4
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 5055-5055
    Abstract: 5055 Background: Cbz + P provides a significant survival benefit vs mitoxantrone + P in pts with mCRPC (Phase III TROPIC study [NCT00417079]; hazard ratio 0.70; p 〈 0.0001). These findings supported the initiation of ongoing Sanofi-funded CUP and EAP (NCT01254279) to provide access to Cbz prior to commercialization and to collect real-life safety data. Methods: Expected enrollment is ~1600 pts with mCRPC from 250 centers worldwide. Pts receive Cbz (25 mg/m 2 Q3W) + P (10 mg oral QD) until progressive disease (PD), death, unacceptable toxicity, physician/pt decision or Cbz commercial availability. Pts are followed until 30 days after last dose. Granulocyte colony-stimulating factor (G-CSF) use is recommended as per ASCO guidance. Results: Interim baseline and safety data from the first 1301 pts treated in 37 countries are now available. Mean age was 68 yrs (22% were ≥ 75 yrs). All pts had an ECOG performance status ≤ 2. Median time from initial prostate cancer diagnosis was 57.6 months and 60% of pts had ≥ 2 metastatic sites; the most common were bone (91%) and lymph nodes (regional 30%, distant 27%). In total, 17% had PD whilst on docetaxel. The median number of Cbz cycles was 6 (range 1–22); median relative dose intensity was 99%. Overall, 837 pts (64%) received G-CSF (n = 123 curative [C] , n = 765 prophylactic [P] and n = 99 [C + P] ). Of 1142 pts (88%) who discontinued Cbz + P, the most common reasons were PD (44%), adverse event (AE; 27%), physician decision (13%) and commercial availability of Cbz (7%). Grade 3–4 AEs possibly related to Cbz + P occurred in 43% of pts; the most frequent were clinical neutropenia (18%), febrile neutropenia (FN; 7%) and diarrhea (4%). Of 80 pts (6%) with AEs leading to death, the AE was related to Cbz + P in 39 pts (3%). Conclusions: These results provide valuable data on Cbz + P treatment in routine clinical practice, confirming the safety results of clinical trials and showing that treatment with Cbz + P is associated with a manageable safety profile. The incidence of FN seems slightly lower than in TROPIC, owing to more frequent use of G-CSF prophylaxis in the CUP and EAP. Clinical trial information: NCT01254279.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 6
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 44, No. suppl_1 ( 2013-02)
    Abstract: Background and purpose: Hemorrhagic transformation is the major complication of reperfusion therapies and carries a high risk of disability and death. Very low cerebral blood volume (VLCBV) and increased blood brain barrier permeability, both markers of severe ischemia, have been proposed as imaging predictors of hemorrhage risk. We aimed to compare the prognostic power of these two approaches using data from the DEFUSE 2 study. Methods: Acute ischemic stroke patients had perfusion-diffusion MRI before and within 12 hr after endovascular therapy. Baseline cerebral blood volume (CBV) maps were generated and the volume of VLCBV (CBV 〈 2.5 th percentile of the normal hemisphere) was calculated. Permeability was assessed using two recirculation parameters: "relative recirculation" (rR): the difference in area encompassed by the observed tissue-concentration curve and a theoretical fit of the first pass bolus; and "percent recovery" (%Recovery): the difference in signal intensity between peak bolus and average post-bolus. Parenchymal hematoma (PH) was defined using ECASS criteria. Reperfusion was defined as 〉 50% reduction in Tmax 〉 6sec lesion volume between baseline and post-procedure MRI. Logistic regression models were compared using Bayesian Information Criterion (BIC). Results: In DEFUSE 2, MRI prior to catheter angiography was performed in 110 patients, 59 had tPA pre-treatment and 25 developed PH. In 103 patients with technically adequate acute perfusion MR, preliminary receiver operating characteristic analysis identified 〉 40%rR and 〈 50%Rec as the optimal thresholds to assess the volume of tissue with increased permeability. In logistic regression, PH was associated with increased VLCBV (p=0.02) and rR permeability (p=0.05) but not %Recovery (p=0.17). The VLCBV model had better fit than rR permeability (BIC difference +2.1) and there was no significant interaction between parameters (p=0.33). Reperfusion was strongly associated with PH (p=0.01) and improved fit of the VLCBV model (BIC +7.2). Conclusions: VLCBV was a stronger predictor of early PH after reperfusion than permeability parameters in patients treated with endovascular therapy.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
    detail.hit.zdb_id: 1467823-8
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  • 7
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 44, No. 1 ( 2013-01), p. 87-93
    Abstract: Two phase 2 studies of alteplase in acute ischemic stroke 3 to 6 hours after onset, Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET; a randomized, controlled, double-blinded trial), and Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study (DEFUSE; open-label, treatment only) using MR imaging-based outcomes have been conducted. We have pooled individual patient data from these to assess the response to alteplase. The primary hypothesis was that alteplase would significantly attenuate infarct growth compared with placebo in mismatch-selected patients using coregistration techniques. Methods— The EPITHET–DEFUSE study datasets were pooled while retaining the original inclusion and exclusion criteria. Significant hypoperfusion was defined as a Tmax delay 〉 6 seconds), and coregistration techniques were used to define MR diffusion-weighted imaging/perfusion-weighted imaging mismatch. Neuroimaging, parameters including reperfusion, recanalization, symptomatic intracerebral hemorrhage, and clinical outcomes were assessed. Alteplase and placebo groups were compared for the primary outcome of infarct growth as well for secondary outcome measures. Results— From 165 patients with adequate MR scans in the EPITHET–DEFUSE pooled data, 121 patients (73.3%) were found to have mismatch. For the primary outcome analysis, 60 patients received alteplase and 41 placebo. Mismatch patients receiving alteplase had significantly attenuated infarct growth compared with placebo ( P =0.025). The reperfusion rate was also increased (62.7% vs 31.7%; P =0.003). Mortality and clinical outcomes were not different between groups. Conclusions— The data provide further evidence that alteplase significantly attenuates infarct growth and increases reperfusion compared with placebo in the 3- to 6- hour time window in patients selected based on MR penumbral imaging. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00238537
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
    detail.hit.zdb_id: 1467823-8
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  • 8
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 42, No. 5 ( 2011-05), p. 1270-1275
    Abstract: To refine the definition of the malignant magnetic resonance imaging profile in acute stroke patients using baseline diffusion-weighted magnetic resonance imaging (DWI) and perfusion-weighted magnetic resonance imaging (PWI) findings from the pooled DEFUSE/EPITHET database. Methods— Patients presenting with acute stroke within 3 to 6 hours from symptom onset were treated with tissue plasminogen activator or placebo. Baseline and follow-up DWI and PWI images from both studies were reprocessed using the same software program. A receiver operating characteristic curve analysis was used to identify Tmax and DWI volumes that optimally predicted poor outcomes (modified Rankin Scale 5–6) at 90 days in patients who achieved reperfusion. Results— Sixty-five patients achieved reperfusion and 46 did not reperfuse. Receiver operating characteristic analysis identified a PWI (Tmax 〉 8 s) volume of 〉 85 mL as the optimal definition of the malignant profile. Eighty-nine percent of malignant profile patients had poor outcome with reperfusion versus 39% of patients without reperfusion ( P =0.02). Parenchymal hematomas occurred more frequently in malignant profile patients who experienced reperfusion versus no reperfusion (67% versus 11%, P 〈 0.01). DWI analysis identified a volume of 80 mL as the best DWI threshold, but this definition was less sensitive than were PWI-based definitions. Conclusions— Stroke patients likely to suffer parenchymal hemorrhages and poor outcomes following reperfusion can be identified from baseline magnetic resonance imaging findings. The current analysis demonstrates that a PWI threshold (Tmax 〉 8 s) of approximately 100 mL is appropriate for identifying these patients. Exclusion of malignant profile patients from reperfusion therapies may substantially improve the efficacy and safety of reperfusion therapies. Clinical Trial Registration Information— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00238537.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2011
    detail.hit.zdb_id: 1467823-8
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  • 9
    In: Cerebrovascular Diseases, S. Karger AG, Vol. 32, No. 4 ( 2011), p. 401-405
    Abstract: 〈 i 〉 Background: 〈 /i 〉 Fluid-attenuated inversion recovery (FLAIR) hyperintensity within an acute cerebral infarct may reflect delayed onset time and increased risk of hemorrhage after thrombolysis. Given the important implications for clinical practice, we examined the prevalence of FLAIR hyperintensity in patients 3–6 h from stroke onset and its relationship to parenchymal hematoma (PH). 〈 i 〉 Methods: 〈 /i 〉 Baseline DWI and FLAIR imaging with subsequent hemorrhage detection (ECASS criteria) were prospectively obtained in patients 3–6 h after stroke onset from the pooled EPITHET and DEFUSE trials. FLAIR hyperintensity within the region of the acute DWI lesion was rated qualitatively (dichotomized as visually obvious or subtle (i.e. only visible after careful windowing)) and quantitatively (using relative signal intensity (RSI)). The association of FLAIR hyperintensity with hemorrhage was then tested alongside established predictors (very low cerebral blood volume (VLCBV) and diffusion (DWI) lesion volume) in logistic regression analysis. 〈 i 〉 Results: 〈 /i 〉 There were 49 patients with pre-treatment FLAIR imaging (38 received tissue plasminogen activator (tPA), 5 developed PH). FLAIR hyperintensity within the region of acute DWI lesion occurred in 48/49 (98%) patients, was obvious in 18/49 (37%) and subtle in 30/49 (61%). Inter-rater agreement was 92% (ĸ = 0.82). The prevalence of obvious FLAIR hyperintensity did not differ between studies obtained in the 3–4.5 h and 4.5–6 h time periods (40% vs. 33%, p = 0.77). PH was poorly predicted by obvious FLAIR hyperintensity (sensitivity 40%, specificity 64%, positive predictive value 11%). In univariate logistic regression, VLCBV (p = 0.02) and DWI lesion volume (p = 0.03) predicted PH but FLAIR lesion volume (p = 0.87) and RSI (p = 0.11) did not. In ordinal logistic regression for hemorrhage grade adjusted for age and baseline stroke severity (NIHSS), increased VLCBV (p = 0.002) and DWI lesion volume (p = 0.003) were associated with hemorrhage but FLAIR lesion volume (p = 0.66) and RSI (p = 0.35) were not. 〈 i 〉 Conclusions: 〈 /i 〉 Visible FLAIR hyperintensity is almost universal 3–6 h after stroke onset and did not predict subsequent hemorrhage in this dataset. Our findings question the value of excluding patients with FLAIR hyperintensity from reperfusion therapies. Larger studies are required to clarify what implications FLAIR-positive lesions have for patient selection.
    Type of Medium: Online Resource
    ISSN: 1015-9770 , 1421-9786
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2011
    detail.hit.zdb_id: 1482069-9
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  • 10
    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 32, No. 1 ( 2012-01), p. 50-56
    Abstract: Diffusion-weighted imaging (DWI) is commonly used to assess irreversibly infarcted tissue but its accuracy is challenged by reports of diffusion lesion reversal (DLR). We investigated the frequency and implications for mismatch classification of DLR using imaging from the EPITHET (Echoplanar Imaging Thrombolytic Evaluation Trial) and DEFUSE (Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution) studies. In 119 patients (83 treated with IV tissue plasminogen activator), follow-up images were coregistered to acute diffusion images and the lesions manually outlined to their maximal visual extent in diffusion space. Diffusion lesion reversal was defined as voxels of acute diffusion lesion that corresponded to normal brain at follow-up (i.e., final infarct, leukoaraiosis, and cerebrospinal fluid (CSF) voxels were excluded from consideration). The appearance of DLR was visually checked for artifacts, the volume calculated, and the impact of adjusting baseline diffusion lesion volume for DLR volume on perfusion-diffusion mismatch analyzed. Median DLR volume reduced from 4.4 to 1.5 mL after excluding CSF/leukoaraiosis. Visual inspection verified 8/119 (6.7%) with true DLR, median volume 2.33 mL. Subtracting DLR from acute diffusion volume altered perfusion—diffusion mismatch ( T max 〉 6 seconds, ratio 〉 1.2) in 3/119 (2.5%) patients. Diffusion lesion reversal between baseline and 3 to 6 hours DWI was also uncommon (7/65, 11%) and often transient. Clinically relevant DLR is uncommon and rarely alters perfusion—diffusion mismatch. The acute diffusion lesion is generally a reliable signature of the infarct core.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2012
    detail.hit.zdb_id: 2039456-1
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