Among patients with acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, less than 40% regain functional independence when treated with intravenous tissue ...plasminogen activator (t-PA) alone. Thrombectomy with the use of a stent retriever, in addition to intravenous t-PA, increases reperfusion rates and may improve long-term functional outcome.
We randomly assigned eligible patients with stroke who were receiving or had received intravenous t-PA to continue with t-PA alone (control group) or to undergo endovascular thrombectomy with the use of a stent retriever within 6 hours after symptom onset (intervention group). Patients had confirmed occlusions in the proximal anterior intracranial circulation and an absence of large ischemic-core lesions. The primary outcome was the severity of global disability at 90 days, as assessed by means of the modified Rankin scale (with scores ranging from 0 no symptoms to 6 death).
The study was stopped early because of efficacy. At 39 centers, 196 patients underwent randomization (98 patients in each group). In the intervention group, the median time from qualifying imaging to groin puncture was 57 minutes, and the rate of substantial reperfusion at the end of the procedure was 88%. Thrombectomy with the stent retriever plus intravenous t-PA reduced disability at 90 days over the entire range of scores on the modified Rankin scale (P<0.001). The rate of functional independence (modified Rankin scale score, 0 to 2) was higher in the intervention group than in the control group (60% vs. 35%, P<0.001). There were no significant between-group differences in 90-day mortality (9% vs. 12%, P=0.50) or symptomatic intracranial hemorrhage (0% vs. 3%, P=0.12).
In patients receiving intravenous t-PA for acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, thrombectomy with a stent retriever within 6 hours after onset improved functional outcomes at 90 days. (Funded by Covidien; SWIFT PRIME ClinicalTrials.gov number, NCT01657461.).
Objective
To assess the utility of computed tomographic (CT) perfusion for selection of patients for endovascular therapy up to 18 hours after symptom onset.
Methods
We conducted a multicenter cohort ...study of consecutive acute stroke patients scheduled to undergo endovascular therapy within 90 minutes after a baseline CT perfusion. Patients were classified as “target mismatch” if they had a small ischemic core and a large penumbra on their baseline CT perfusion. Reperfusion was defined as >50% reduction in critical hypoperfusion between the baseline CT perfusion and the 36‐hour follow‐up magnetic resonance imaging.
Results
Of the 201 patients enrolled, 190 patients with an adequate baseline CT perfusion study who underwent angiography were included (mean age = 66 years, median NIH Stroke Scale NIHSS = 16, median time from symptom onset to endovascular therapy = 5.2 hours). Rate of reperfusion was 89%. In patients with target mismatch (n = 131), reperfusion was associated with higher odds of favorable clinical response, defined as an improvement of ≥8 points on the NIHSS (83% vs 44%; p = 0.002, adjusted odds ratio OR = 6.6, 95% confidence interval CI = 2.1–20.9). This association did not differ between patients treated within 6 hours (OR = 6.4, 95% CI = 1.5–27.8) and those treated > 6 hours after symptom onset (OR = 13.7, 95% CI = 1.4–140).
Interpretation
The robust association between endovascular reperfusion and good outcome among patients with the CT perfusion target mismatch profile treated up to 18 hours after symptom onset supports a randomized trial of endovascular therapy in this patient population. Ann Neurol 2017;81:849–856
Postoperative delirium is frequent in older adults and is associated with postoperative neurocognitive disorder (PND). Studies evaluating perioperative medication use and delirium have generally ...evaluated medications in aggregate and been poorly controlled; the association between perioperative medication use and PND remains unclear. We sought to evaluate the association between medication use and postoperative delirium and PND in older adults undergoing major elective surgery.
This is a secondary analysis of a prospective cohort study of adults ≥70 years without dementia undergoing major elective surgery. Patients were interviewed preoperatively to determine home medication use. Postoperatively, daily hospital use of 7 different medication classes listed in guidelines as risk factors for delirium was collected; administration before delirium was verified. While hospitalized, patients were assessed daily for delirium using the Confusion Assessment Method and a validated chart review method. Cognition was evaluated preoperatively and 1 month after surgery using a neurocognitive battery. The association between prehospital medication use and postoperative delirium was assessed using a generalized linear model with a log link function, controlling for age, sex, type of surgery, Charlson comorbidity index, and baseline cognition. The association between daily postoperative medication use (when class exposure ≥5%) and time to delirium was assessed using time-varying Cox models adjusted for age, sex, surgery type, Charlson comorbidity index, Acute Physiology and Chronic Health Evaluation (APACHE)-II score, and baseline cognition. Mediation analysis was utilized to evaluate the association between medication use, delirium, and cognitive change from baseline to 1 month.
Among 560 patients enrolled, 134 (24%) developed delirium during hospitalization. The multivariable analyses revealed no significant association between prehospital benzodiazepine (relative risk RR, 1.44; 95% confidence interval CI, 0.85-2.44), beta-blocker (RR, 1.38; 95% CI, 0.94-2.05), NSAID (RR, 1.12; 95% CI, 0.77-1.62), opioid (RR, 1.22; 95% CI, 0.82-1.82), or statin (RR, 1.34; 95% CI, 0.92-1.95) exposure and delirium. Postoperative hospital benzodiazepine use (adjusted hazard ratio aHR, 3.23; 95% CI, 2.10-4.99) was associated with greater delirium. Neither postoperative hospital antipsychotic (aHR, 1.48; 95% CI, 0.74-2.94) nor opioid (aHR, 0.82; 95% CI, 0.62-1.11) use before delirium was associated with delirium. Antipsychotic use (either presurgery or postsurgery) was associated with a 0.34 point (standard error, 0.16) decrease in general cognitive performance at 1 month through its effect on delirium (P = .03), despite no total effect being observed.
Administration of benzodiazepines to older adults hospitalized after major surgery is associated with increased postoperative delirium. Association between inhospital, postoperative medication use and cognition at 1 month, independent of delirium, was not detected.
Objective
Within the context of a prospective randomized trial (SWIFT PRIME), we assessed whether early imaging of stroke patients, primarily with computed tomography (CT) perfusion, can estimate the ...size of the irreversibly injured ischemic core and the volume of critically hypoperfused tissue. We also evaluated the accuracy of ischemic core and hypoperfusion volumes for predicting infarct volume in patients with the target mismatch profile.
Methods
Baseline ischemic core and hypoperfusion volumes were assessed prior to randomized treatment with intravenous (IV) tissue plasminogen activator (tPA) alone versus IV tPA + endovascular therapy (Solitaire stent‐retriever) using RAPID automated postprocessing software. Reperfusion was assessed with angiographic Thrombolysis in Cerebral Infarction scores at the end of the procedure (endovascular group) and Tmax > 6‐second volumes at 27 hours (both groups). Infarct volume was assessed at 27 hours on noncontrast CT or magnetic resonance imaging (MRI).
Results
A total of 151 patients with baseline imaging with CT perfusion (79%) or multimodal MRI (21%) were included. The median baseline ischemic core volume was 6ml (interquartile range = 0–16). Ischemic core volumes correlated with 27‐hour infarct volumes in patients who achieved reperfusion (r = 0.58, p < 0.0001). In patients who did not reperfuse (<10% reperfusion), baseline Tmax > 6‐second lesion volumes correlated with 27‐hour infarct volume (r = 0.78, p = 0.005). In target mismatch patients, the union of baseline core and early follow‐up Tmax > 6‐second volume (ie, predicted infarct volume) correlated with the 27‐hour infarct volume (r = 0.73, p < 0.0001); the median absolute difference between the observed and predicted volume was 13ml.
Interpretation
Ischemic core and hypoperfusion volumes, obtained primarily from CT perfusion scans, predict 27‐hour infarct volume in acute stroke patients who were treated with reperfusion therapies. ANN NEUROL 2016;79:76–89
Clinical trials have demonstrated improved 90-day outcomes for patients with acute ischemic stroke treated with stent retriever thrombectomy plus tissue-type plasminogen activator (SST+tPA) compared ...with tPA. Previous studies suggested that this strategy may be cost-effective, but models were derived from pooled data and older assumptions.
In this prospective economic substudy conducted alongside the SWIFT-PRIME trial (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke), in-trial costs were measured for patients using detailed medical resource utilization and hospital billing data. Utility weights were assessed at 30 and 90 days using the EuroQol-5 dimension questionnaire. Post-trial costs and life-expectancy were estimated for each surviving patient using a model based on trial data and inputs derived from a contemporary cohort of ischemic stroke survivors.
Index hospitalization costs were $17 183 per patient higher for SST+tPA than for tPA ($45 761 versus $28 578; P<0.001), driven by initial procedure costs. Between discharge and 90 days, costs were $4904 per patient lower for SST+tPA than for tPA ($11 270 versus $16 174; P=0.014); total 90-day costs remained higher with SST+tPA ($57 031 versus $44 752; P<0.001). Higher utility values for SST+tPA led to higher in-trial quality-adjusted life years (0.131 versus 0.105; P=0.005). In lifetime projections, SST+tPA was associated with substantial gains in quality-adjusted life years (6.79 versus 5.05), cost savings of $23 203 per patient and was economically dominant when compared with tPA in 90% of bootstrap replicates.
Among patients with acute ischemic stroke enrolled in the SWIFT-PRIME trial, SST increased initial treatment costs, but was projected to improve quality-adjusted life-expectancy and reduce healthcare costs over a lifetime horizon compared with tPA.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01657461.
The Super Dual Auroral Radar Network (SuperDARN) is a network of high-frequency (HF) radars located in the high- and mid-latitude regions of both hemispheres that is operated under international ...cooperation. The network was originally designed for monitoring the dynamics of the ionosphere and upper atmosphere in the high-latitude regions. However, over the last approximately 15 years, SuperDARN has expanded into the mid-latitude regions. With radar coverage that now extends continuously from auroral to sub-auroral and mid-latitudes, a wide variety of new scientific findings have been obtained. In this paper, the background of mid-latitude SuperDARN is presented at first. Then, the accomplishments made with mid-latitude SuperDARN radars are reviewed in five specified scientific and technical areas: convection, ionospheric irregularities, HF propagation analysis, ion-neutral interactions, and magnetohydrodynamic (MHD) waves. Finally, the present status of mid-latitude SuperDARN is updated and directions for future research are discussed.
Rationale
Early reperfusion in patients experiencing acute ischemic stroke is critical, especially for patients with large vessel occlusion who have poor prognosis without revascularization. ...Solitaire™ stent retriever devices have been shown to immediately restore vascular perfusion safely, rapidly, and effectively in acute ischemic stroke patients with large vessel occlusions.
Aim
The aim of the study was to demonstrate that, among patients with large vessel, anterior circulation occlusion who have received intravenous tissue plasminogen activator, treatment with Solitaire revascularization devices reduces degree of disability 3 months post stroke.
Design
The study is a global multicenter, two-arm, prospective, randomized, open, blinded end-point trial comparing functional outcomes in acute ischemic stroke patients who are treated with either intravenous tissue plasminogen activator alone or intravenous tissue plasminogen activator in combination with the Solitaire device. Up to 833 patients will be enrolled.
Procedures
Patients who have received intravenous tissue plasminogen activator are randomized to either continue with intravenous tissue plasminogen activator alone or additionally proceed to neurothrombectomy using the Solitaire device within six-hours of symptom onset.
Study Outcomes
The primary end-point is 90-day global disability, assessed with the modified Rankin Scale (mRS). Secondary outcomes include mortality at 90 days, functional independence (mRS ≤ 2) at 90 days, change in National Institutes of Health Stroke Scale at 27 h, reperfusion at 27 h, and thrombolysis in cerebral infarction 2b/3 flow at the end of the procedure.
Analysis
Statistical analysis will be conducted using simultaneous success criteria on the overall distribution of modified Rankin Scale (Rankin shift) and proportions of subjects achieving functional independence (mRS 0–2).
Introduction Current technologies including EEG and near infrared pulse oximetry for non‐invasive monitoring of cerebral blood flow during cardiac surgery have proven inadequate for perioperative ...stroke risk mitigation. Cerebral arterial flow velocity is an excellent indicator of cerebral blood flow making transcranial doppler ultrasound (TCD) an excellent alternative technology for operating room continuous cerebral monitoring. To date, TCD utilization in the operating room has been limited due to frequent movement‐related loss of signal requiring nearly continuous manual probe readjustment. The recent development of fully autonomous robotic TCD (aTCD) has overcome these technical limitations, opening the door for real‐time continuous noninvasive cerebral blood flow monitoring with simultaneous emboli detection. Methods A 47‐year‐old female patient was found to have preoperative complete occlusion of the proximal brachiocephalic artery producing a double cerebral steal phenomenon with retrograde flow in the right internal carotid and vertebral arteries into the subclavian. A preoperative aTCD study disclosed baseline markedly diminished blood flow in the right middle cerebral artery (MCA) fed exclusively by small‐diameter collaterals via the circle of Willis.Intraoperatively, robotic aTCD was used to continuously monitor blood flow in the bilateral MCAs and perform emboli detection. In response to movement‐related signal loss, the robotic aTCD autonomously adjusted the probe position to maintain continuous MCA insonation. Results Shortly after intubation, a small drop in mean arterial pressure led to a near‐total loss of cerebral perfusion to the entire right hemisphere. This perfusion decrease was detected by aTCD, triggering the anesthesiologist to rapidly correct blood pressure to ensure adequate cerebral perfusion as confirmed by the robotic system. The patient was then placed on bypass pump with deployment of a temporary Y‐graft from the pump to the subclavian artery distal to the vertebral branch point and to the aorta to temporarily reverse the double cerebral steal. Coronary bypass was then performed, throughout which cerebral flow velocities were monitored continuously with aTCD and maintained in the safe cerebral perfusion range by adjusting pump pressures. Following a three‐vessel coronary bypass graft, permanent brachiocephalic artery bypass grafts were placed from the proximal aorta to the right subclavian and the proximal common carotid artery.Postoperative aTCD disclosed correction of the previously diminished blood flow detected in the right MCA preoperatively. Brain MRI postoperatively confirmed the absence of acute stroke. Conclusions This case represents the first use of robotic aTCD for real time continuous cerebral blood flow monitoring and optimization during complex cardiac surgery. Our experience suggests that aTCD may improve patient outcomes, particularly during high‐risk cardiac surgical and interventional procedures. Further studies of this promising technology are now needed.
The positive treatment effect of endovascular therapy (EVT) is assumed to be caused by the preservation of brain tissue. It remains unclear to what extent the treatment-related reduction in follow-up ...infarct volume (FIV) explains the improved functional outcome after EVT in patients with acute ischemic stroke.
To study whether FIV mediates the relationship between EVT and functional outcome in patients with acute ischemic stroke.
Patient data from 7 randomized multicenter trials were pooled. These trials were conducted between December 2010 and April 2015 and included 1764 patients randomly assigned to receive either EVT or standard care (control). Follow-up infarct volume was assessed on computed tomography or magnetic resonance imaging after stroke onset. Mediation analysis was performed to examine the potential causal chain in which FIV may mediate the relationship between EVT and functional outcome. A total of 1690 patients met the inclusion criteria. Twenty-five additional patients were excluded, resulting in a total of 1665 patients, including 821 (49.3%) in the EVT group and 844 (50.7%) in the control group. Data were analyzed from January to June 2017.
The 90-day functional outcome via the modified Rankin Scale (mRS).
Among 1665 patients, the median (interquartile range IQR) age was 68 (57-76) years, and 781 (46.9%) were female. The median (IQR) time to FIV measurement was 30 (24-237) hours. The median (IQR) FIV was 41 (14-120) mL. Patients in the EVT group had significantly smaller FIVs compared with patients in the control group (median IQR FIV, 33 11-99 vs 51 18-134 mL; P = .007) and lower mRS scores at 90 days (median IQR score, 3 1-4 vs 4 2-5). Follow-up infarct volume was a predictor of functional outcome (adjusted common odds ratio, 0.46; 95% CI, 0.39-0.54; P < .001). Follow-up infarct volume partially mediated the relationship between treatment type with mRS score, as EVT was still significantly associated with functional outcome after adjustment for FIV (adjusted common odds ratio, 2.22; 95% CI, 1.52-3.21; P < .001). Treatment-reduced FIV explained 12% (95% CI, 1-19) of the relationship between EVT and functional outcome.
In this analysis, follow-up infarct volume predicted functional outcome; however, a reduced infarct volume after treatment with EVT only explained 12% of the treatment benefit. Follow-up infarct volume as measured on computed tomography and magnetic resonance imaging is not a valid proxy for estimating treatment effect in phase II and III trials of acute ischemic stroke.
Follow-up infarct volume (FIV) has been recommended as an early indicator of treatment efficacy in patients with acute ischemic stroke. Questions remain about the optimal imaging approach for FIV ...measurement.
To examine the association of FIV with 90-day modified Rankin Scale (mRS) score and investigate its dependency on acquisition time and modality.
Data of seven trials were pooled. FIV was assessed on follow-up (12 hours to 2 weeks) CT or MRI. Infarct location was defined as laterality and involvement of the Alberta Stroke Program Early CT Score regions. Relative quality and strength of multivariable regression models of the association between FIV and functional outcome were assessed. Dependency of imaging modality and acquisition time (≤48 hours vs >48 hours) was evaluated.
Of 1665 included patients, 83% were imaged with CT. Median FIV was 41 mL (IQR 14-120). A large FIV was associated with worse functional outcome (OR=0.88(95% CI 0.87 to 0.89) per 10 mL) in adjusted analysis. A model including FIV, location, and hemorrhage type best predicted mRS score. FIV of ≥133 mL was highly specific for unfavorable outcome. FIV was equally strongly associated with mRS score for assessment on CT and MRI, even though large differences in volume were present (48 mL (IQR 15-131) vs 22 mL (IQR 8-71), respectively). Associations of both early and late FIV assessments with outcome were similar in strength (ρ=0.60(95% CI 0.56 to 0.64) and ρ=0.55(95% CI 0.50 to 0.60), respectively).
In patients with an acute ischemic stroke due to a proximal intracranial occlusion of the anterior circulation, FIV is a strong independent predictor of functional outcome and can be assessed before 48 hours, oneither CT or MRI.
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