Characteristics of misclassified ct perfusion ischemic core in patients with acute ischemic stroke

Background CT perfusion (CTP) is used to estimate the extent of ischemic core and penumbra in patients with acute ischemic stroke. CTP reliability, however, is limited. This study aims to identify regions misclassified as ischemic core on CTP, using infarct on follow-up noncontrast CT. We aim to assess differences in volumetric and perfusion characteristics in these regions compared to areas that ended up as infarct on follo

Stroke Etiology and Thrombus Computed Tomography Characteristics in Patients With Acute Ischemic Stroke:A MR CLEAN Registry Substudy

Background and Purpose - If a relationship between stroke etiology and thrombus computed tomography characteristics exists, assessing these characteristics in clinical practice could serve as a useful additional diagnostic tool for the identification of stroke subtype. Our purpose was to study the association of stroke etiology and thrombus computed tomography characteristics in patients with acute ischemic stroke due to a large vessel occlusion. Methods - For 1429 consecutive patients enrolled in the MR CLEAN Registry, we determined stroke cause as defined by the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria. The association of stroke etiology with the hyperdense artery sign, clot burden score, and thrombus location was estimated with univariable and multivariable binary and ordinal logistic regression. Additionally, for 367 patients with available thin-section imaging, we assessed the association of stroke etiology with absolute and relative thrombus attenuation, distance from internal carotid artery-terminus to thrombus, thrombus length, and thrombus attenuation increase with univariable and multivariable linear regression. Results - Compared with cardioembolic strokes, noncardioembolic strokes were associated with presence of hyperdense artery sign (odds ratio, 2.2 [95% CI, 1.6-3.0]), lower clot burden score (common odds ratio, 0.4 [95% CI, 0.3-0.6]), shift towards a more proximal thrombus location (common odds ratio, 0.2 [95% CI, 0.2-0.3]), higher absolute thrombus attenuation (β, 3.6 [95% CI, 0.9-6.4]), decrease in distance from the ICA-terminus (β, -5.7 [95% CI, -8.3 to -3.0]), and longer thrombi (β, 8.6 [95% CI, 6.5-10.7]), based on univariable analysis. Thrombus characteristics of strokes with undetermined cause were similar to those of cardioembolic strokes. Conclusions - Thrombus computed tomography characteristics of cardioembolic stroke are distinct from those of noncardioembolic stroke. Additionally, our study supports the general hypothesis that many cryptogenic strokes have a cardioembolic cause. Further research should focus on the use of thrombus computed tomography characteristics as a diagnostic tool for stroke cause in clinical practice

Admission Blood Pressure in Relation to Clinical Outcomes and Successful Reperfusion After Endovascular Stroke Treatment

BACKGROUND AND PURPOSE: Optimal blood pressure (BP) targets before endovascular treatment (EVT) for acute ischemic stroke are unknown. We aimed to assess the relation between admission BP and clinical outcomes and successful reperfusion after EVT. METHODS: We used data from the MR CLEAN (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry, an observational, prospective, nationwide cohort study of patients with ischemic stroke treated with EVT in routine clinical practice in the Netherlands. Baseline systolic BP (SBP) and diastolic BP (DBP) were recorded on admission. The primary outcome was the score on the modified Rankin Scale at 90 days. Secondary outcomes included successful reperfusion (extended Thrombolysis in Cerebral Infarction score 2B-3), symptomatic intracranial hemorrhage, and 90-day mortality. Multivariable logistic and linear regression were used to assess the associations of SBP and DBP with outcomes. The relations between BPs and outcomes were tested for nonlinearity. Parameter estimates were calculated per 10 mm Hg increase or decrease in BP. RESULTS: We included 3180 patients treated with EVT between March 2014 and November 2017. The relations between admission SBP and DBP with 90-day modified Rankin Scale scores and mortality were J-shaped, with inflection points around 150 and 81 mm Hg, respectively. An increase in SBP above 150 mm Hg was associated with poor functional outcome (adjusted common odds ratio, 1.09 [95% CI, 1.04-1.15]) and mortality at 90 days (adjusted odds ratio, 1.09 [95% CI, 1.03-1.16]). Following linear relationships, higher SBP was associated with a lower probability of successful reperfusion (adjusted odds ratio, 0.97 [95% CI, 0.94-0.99]) and with the occurrence of symptomatic intracranial hemorrhage (adjusted odds ratio, 1.06 [95% CI, 0.99-1.13]). Results for DBP were largely similar. CONCLUSIONS: In patients with acute ischemic stroke treated with EVT, higher admission BP is associated with lower probability of successful reperfusion and with poor clinical outcomes. Further research is needed to investigate whether these patients benefit from BP reduction before EVT

Are Insider Sales Always Bad News? Evidence On Large Sales By Key Insiders

Investors often scrutinize stock trades by corporate insiders, hoping to infer the nature of any privileged information which may have motivated the trades. Conventional wisdom suggests that sales of stock by insiders reveal negative information; this interpretation is supported by empirical work such as the series of papers by Seyhun. However, this common interpretation fails to distinguish between sales by atomistic insiders and sales by controlling blockholders.  In this paper, I present evidence which suggests that sales by controlling insiders should not be considered bad news. Using both a series of logit regressions and traditional event-study tests, I examine the relationship between a firm's performance and the willingness of its controlling shareholder to sell a significant proportion of his shares. I find that firm value is just as likely to rise on the news of large insider sales as it is to fall, so that large sales need not imply negative private information.  One possible explanation for a positive response to a controlling blockholder's large sale is that such a sale makes the insider vulnerable to meaningful oversight by outside shareholders. Thus, a large sale may be a signal of the insider's willingness to expose himself to shareholder monitoring and discipline. However, regardless of the interpretation, the empirical evidence presented in the paper forces the conclusion that it is inappropriate to interpret all insider sales as bad news: insider sales occur in a variety of contexts, and creating buy/sell rules which ignore those contexts is simplistic and erroneous

病院紹介

BACKGROUND: Endovascular or intra-arterial treatment (IAT) increases the likelihood of recanalization in patients with acute ischemic stroke caused by a proximal intracranial arterial occlusion. However, a beneficial effect of IAT on functional recovery in patients with acute ischemic stroke remains unproven. The aim of this study is to assess the effect of IAT on functional outcome in patients with acute ischemic stroke. Additionally, we aim to assess the safety of IAT, and the effect on recanalization of different mechanical treatment modalities. METHODS/DESIGN: A multicenter randomized clinical trial with blinded outcome assessment. The active comparison is IAT versus no IAT. IAT may consist of intra-arterial thrombolysis with alteplase or urokinase, mechanical treatment or both. Mechanical treatment refers to retraction, aspiration, sonolysis, or use of a retrievable stent (stent-retriever). Patients with a relevant intracranial proximal arterial occlusion of the anterior circulation, who can be treated within 6 hours after stroke onset, are eligible. Treatment effect will be estimated with ordinal logistic regression (shift analysis); 500 patients will be included in the trial for a power of 80% to detect a shift leading to a decrease in dependency in 10% of treated patients. The primary outcome is the score on the modified Rankin scale at 90 days. Secondary outcomes are the National Institutes of Health stroke scale score at 24 hours, vessel patency at 24 hours, infarct size on day 5, and the occurrence of major bleeding during the first 5 days. DISCUSSION: If IAT leads to a 10% absolute reduction in poor outcome after stroke, careful implementation of the intervention could save approximately 1% of all new stroke cases from death or disability annually. TRIAL REGISTRATION: NTR1804 (7 May 2009)/ISRCTN10888758 (24 July 2012)

Healthy life-year costs of treatment speed from arrival to endovascular thrombectomy in patients with ischemic stroke: a meta-analysis of individual patient data from 7 randomized clinical trials

This meta-analysis evaluates outcomes along the full health-related quality-of-life range associated with time to endovascular thrombectomy in patients with ischemic stroke.Question What are the lifetime consequences associated with care process delays in patients with ischemic stroke who are treated with endovascular thrombectomy? Findings In this meta-analysis of pooled individual patient data from 406 adults in 7 randomized trials, delays in delivering endovascular thrombectomy were associated with marked reductions in healthy life-years after treatment. In the time interval from hospital arrival to endovascular procedure start, every 1 second of delay was associated with loss of 2.2 hours of healthy life. Meaning In this study, care delays in delivering endovascular thrombectomy to ischemic stroke patients were associated with substantial losses of healthy life-years; health care organization and workflow optimization should be a priority to facilitate faster reperfusion for acute stroke patients.Importance The benefits of endovascular thrombectomy (EVT) are time dependent. Prior studies may have underestimated the time-benefit association because time of onset is imprecisely known. Objective To assess the lifetime outcomes associated with speed of endovascular thrombectomy in patients with acute ischemic stroke due to large-vessel occlusion (LVO). Data Sources PubMed was searched for randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time, and for which a peer-reviewed, complete primary results article was published by August 1, 2020. Study Selection All randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time were included. Data Extraction/Synthesis Patient-level data regarding presenting clinical and imaging features and functional outcomes were pooled from the 7 retrieved randomized clinical trials of stent retriever thrombectomy devices (entirely or predominantly) vs medical therapy. All 7 identified trials published in a peer-reviewed journal (by August 1, 2020) contributed data. Detailed time metrics were collected including last known well-to-door (LKWTD) time; last known well/onset-to-puncture (LKWTP) time; last known well-to-reperfusion (LKWR) time; door-to-puncture (DTP) time; and door-to-reperfusion (DTR) time. Main Outcomes and Measures Change in healthy life-years measured as disability-adjusted life-years (DALYs). DALYs were calculated as the sum of years of life lost (YLL) owing to premature mortality and years of healthy life lost because of disability (YLD). Disability weights were assigned using the utility-weighted modified Rankin Scale. Age-specific life expectancies without stroke were calculated from 2017 US National Vital Statistics. Results Among the 781 EVT-treated patients, 406 (52.0%) were early-treated (LKWTP 4-12 hours). In early-treated patients, LKWTD was 188 minutes (interquartile range, 151.3-214.8 minutes) and DTP 105 minutes (interquartile range, 76-135 minutes). Among the 298 of 380 (78.4%) patients with substantial reperfusion, median DTR time was 145.0 minutes (interquartile range, 111.5-185.5 minutes). Care process delays were associated with worse clinical outcomes in LKW-to-intervention intervals in early-treated patients and in door-to-intervention intervals in early-treated and late-treated patients, and not associated with LKWTD intervals, eg, in early-treated patients, for each 10-minute delay, healthy life-years lost were DTP 1.8 months vs LKWTD 0.0 months; P < .001. Considering granular time increments, the amount of healthy life-time lost associated with each 1 second of delay was DTP 2.2 hours and DTR 2.4 hours. Conclusions and Relevance In this study, care delays were associated with loss of healthy life-years in patients with acute ischemic stroke treated with EVT, particularly in the postarrival time period. The finding that every 1 second of delay was associated with loss of 2.2 hours of healthy life may encourage continuous quality improvement in door-to-treatment times.Paroxysmal Cerebral Disorder

Relationship between primary stroke center volume and time to endovascular thrombectomy in acute ischemic stroke

Background and purpose We investigated whether the annual volume of patients with acute ischemic stroke referred from a primary stroke center (PSC) for endovascular treatment (EVT) is associated with treatment times and functional outcome. Methods We used data from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) registry (2014-2017). We included patients with acute ischemic stroke of the anterior circulation who were transferred from a PSC to a comprehensive stroke center (CSC) for EVT. We examined the association between EVT referral volume of PSCs and treatment times and functional outcome using multivariable regression modeling. The main outcomes were time from arrival at the PSC to groin puncture (PSC-door-to-groin time), adjusted for estimated ambulance travel times, time from arrival at the CSC to groin puncture (CSC-door-to-groin time), and modified Rankin Scale (mRS) score at 90 days after stroke. Results Of the 3637 patients in the registry, 1541 patients (42%) from 65 PSCs were included. Mean age was 71 years (SD +/- 13.3), median National Institutes of Health Stroke Scale score was 16 (interquartile range [IQR]: 12-19), and median time from stroke onset to arrival at the PSC was 53 min (IQR: 38-90). Eighty-three percent had received intravenous thrombolysis. EVT referral volume was not associated with PSC-door-to-groin time (adjusted coefficient: -0.49 min/annual referral, 95% confidence interval [CI]: -1.27 to 0.29), CSC-door-to-groin time (adjusted coefficient: -0.34 min/annual referral, 95% CI: -0.69 to 0.01) or 90-day mRS score (adjusted common odds ratio: 0.99, 95% CI: 0.96-1.01). Conclusions In patients transferred from a PSC for EVT, higher PSC volumes do not seem to translate into better workflow metrics or patient outcome.Neuro Imaging Researc

Prediction of outcome and endovascular treatment benefit validation and update of the MR PREDICTS decision tool

BACKGROUND AND PURPOSE: Benefit of early endovascular treatment (EVT) for ischemic stroke varies considerably among patients. The MR PREDICTS decision tool, derived from MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), predicts outcome and treatment benefit based on baseline characteristics. Our aim was to externally validate and update MR PREDICTS with data from international trials and daily clinical practice.METHODS: We used individual patient data from 6 randomized controlled trials within the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) collaboration to validate the original model. Then, we updated the model and performed a second validation with data from the observational MR CLEAN Registry. Primary outcome was functional independence (defined as modified Rankin Scale score 0-2) 3 months after stroke. Treatment benefit was defined as the difference between the probability of functional independence with and without EVT. Discriminative performance was evaluated using a concordance (C) statistic.RESULTS: We included 1242 patients from HERMES (633 assigned to EVT, 609 assigned to control) and 3156 patients from the MR CLEAN Registry (all of whom underwent EVT within 6.5 hours). The C-statistic for functional independence was 0.74 (95% CI, 0.72-0.77) in HERMES and, after model updating, 0.80 (0.78-0.82) in the Registry. Median predicted treatment benefit of routinely treated patients (Registry) was 10.3% (interquartile range, 5.8%-14.4%). Patients with low (<1%) predicted treatment benefit (n=135/3156 [4.3%]) had low rates of functional independence, irrespective of reperfusion status, suggesting potential absence of treatment benefit. The updated model was made available online for clinicians and researchers at .CONCLUSIONS: Because of the substantial treatment effect and small potential harm of EVT, most patients arriving within 6 hours at an endovascular-capable center should be treated regardless of their clinical characteristics. MR PREDICTS can be used to support clinical judgement when there is uncertainty about the treatment indication, when resources are limited, or before a patient is to be transferred to an endovascular-capable center.Analysis and support of clinical decision makingDevelopment and application of statistical models for medical scientific researc

Intracranial Cerebrospinal Fluid Volume as a Predictor of Malignant Middle Cerebral Artery Infarction

Background and Purpose— Predicting malignant middle cerebral artery (MCA) infarction can help to identify patients who may benefit from preventive decompressive surgery. We aimed to investigate the association between the ratio of intracranial cerebrospinal fluid (CSF) volume to intracranial volume (ICV) and malignant MCA infarction. Methods— Patients with an occlusion proximal to the M3 segment of the MCA were selected from the DUST (Dutch Acute Stroke Study). Admission imaging included noncontrast computed tomography (CT), CT perfusion, and CT angiography. Patient characteristics and CT findings were collected. The ratio of intracranial CSF volume to ICV (CSF/ICV) was quantified on admission thin-slice noncontrast CT. Malignant MCA infarction was defined as a midline shift of >5 mm on follow-up noncontrast CT, which was performed 3 days after the stroke or in case of clinical deterioration. To test the association between CSF/ICV and malignant MCA infarction, odds ratios and 95% CIs were calculated for 3 multivariable models by using binary logistic regression. Model performances were compared by using the likelihood ratio test. Results— Of the 286 included patients, 35 (12%) developed malignant MCA infarction. CSF/ICV was independently associated with malignant MCA infarction in 3 multivariable models: (1) with age and admission National Institutes of Health Stroke Scale (odds ratio, 3.3; 95% CI, 1.1–11.1), (2) with admission National Institutes of Health Stroke Scale and poor collateral score (odds ratio, 7.0; 95% CI, 2.6–21.3), and (3) with terminal internal carotid artery or proximal M1 occlusion and poor collateral score (odds ratio, 7.7; 95% CI, 2.8–23.9). The performance of model 1 (areas under the receiver operating characteristic curves, 0.795 versus 0.824; P=0.033), model 2 (areas under the receiver operating characteristic curves, 0.813 versus 0.850; P<0.001), and model 3 (areas under the receiver operating characteristic curves, 0.811 versus 0.856; P<0.001) improved significantly after adding CSF/ICV. Conclusions— The CSF/ICV ratio is associated with malignant MCA infarction and has added value to clinical and imaging prediction models in limited numbers of patients