Author: "Timothy Ang" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Timothy Ang"' showing total 31 results

Start Over Author "Timothy Ang"

31 results on '"Timothy Ang"'

1. Relationship Between Baseline Infarct and Clinical Outcome in Pediatric Large‐Vessel Occlusion Ischemic Stroke

Author: Kartik D. Bhatia, Carmen Parra‐Farinas, Elizabeth Pulcine, Nomazulu Dlamini, Ian Andrews, Sachin Gupta, Richard Webster, Christopher Troedson, Russell C. Dale, John Worthington, Kylie Tastula, Timothy Ang, Andrew Cheung, Nathan Manning, Ferdinand Miteff, Christina Miteff, and Prakash Muthusami
Subjects: ASPECTS, large‐vessel occlusion, mechanical thrombectomy, pediatric stroke, Neurology. Diseases of the nervous system, RC346-429, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background In adults with large‐vessel occlusion stroke, the extent of the baseline infarct measured using the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) predicts outcome and is used during patient selection for mechanical thrombectomy. The relationship between ASPECTS and clinical outcome is unknown in pediatric large‐vessel occlusion stroke. Methods Secondary analysis of a retrospective multicenter case–control study assessing mechanical thrombectomy versus medical management alone for pediatric large‐vessel occlusion stroke across 5 centers in Australia and Canada from 2011 to 2022. ASPECTS was measured on baseline computed tomography or magnetic resonance imaging–diffusion‐weighted imaging while blinded to clinical outcome and treatment status. The relationship between ASPECTS and pediatric modified Rankin scale scores at 3 months following stroke was assessed using ordinal logistic regression. Results In total, n = 24 thrombectomy patients (F = 10, mean age, 11.3 years [SD, 4.36]) and n = 24 control patients (F = 10, mean age, 10.2 years [SD, 4.32) were included. Mean ASPECTS was 6.3 (SD, 2.37) in the thrombectomy group and 6.1 (SD, 2.64) in the control group. In patients undergoing thrombectomy, baseline ASPECTS significantly correlated with pediatric modified Rankin scale scores at 3 months (odds ratio, 1.58 [95% CI, 1.10–2.27]; P = 0.013). In control patients, there was no significant correlation (odds ratio, 1.17 [95% CI, 0.87–1.55]; P = 0.298). Six of 7 thrombectomy patients with a large baseline infarct (ASPECTS
Published: 2024
Full Text: View/download PDF

2. Rollout of a statewide Australian telestroke network including virtual reality training is associated with improved hyperacute stroke workflow metrics and thrombolysis rate

Author: Carlos Garcia-Esperon, Steven Maltby, Ken Butcher, Md Golam Hasnain, Beng Lim Alvin Chew, William O'Brien, James W. Evans, Timothy Ang, Leon Edwards, Christopher Blair, Candice Delcourt, Mark W. Parsons, Ferdinand Miteff, Jason Dizon, David Lambkin, Daniel Barker, Murielle G. Kluge, John H. Wiggers, Christopher R. Levi, Neil J. Spratt, Frederick Rohan Walker, The Virtual Reality NSW Telestroke Group, Chris Oldmeadow, Rachel Peake, Jaclyn Birnie, Amanda Buzio, Jennifer Steel, Kim Parrey, Emma McCartney, Thembelihle Mathe, Matthew Shepherd, Lisa Dark, James Hughes, Kate Jackson, Claire Gill, Courtney Dixon, Skye Russell, and Natalie Wilson
Subjects: telestroke, virtual reality, medical education, stroke workflow, thrombolysis, Medicine
Abstract: BackgroundTelestroke networks aim to address variability in both quality and access to stroke care in rural areas, by providing remote access to expert stroke neurologists. Implementation of telestroke requires adaptation of workflow processes and education. We previously developed virtual reality (VR) workflow training and documented acceptability, utility and feasibility. The effects on acute stroke treatment metrics have not been previously described.AimsThe overall aim was to improve hyperacute stroke metrics and shorten the time-to-reperfusion therapy administration in rural settings.MethodsThis study applies a natural experiment approach, collecting stroke metric data during transition from a pre-existing pilot to a statewide telestroke service at five rural hospitals. Pre- and post-intervention data included baseline patient demographics and assessment, diagnosis, and treatment delivery metrics. The primary study outcome was door-to-decision time (thrombolysis and endovascular thrombectomy). Secondary outcomes included door-to-computerized tomography time, door-to-thrombolysis time and proportion of patients receiving thrombolysis or thrombectomy treatment. Usage data relating to the VR stroke workflow training of interprofessional healthcare professionals was automatically captured via Wi-Fi. Statistical comparisons of clinical metrics between the pre- and post-intervention time periods, defined as the timeframes before and after VR deployment, were performed.ResultsA total of 2,683 patients were included (April 2013–December 2022); 1910 pre- and 773 post-intervention. All acute stroke time metrics significantly improved post-intervention. The primary outcome, door-to-decision time, decreased from 80 min [56–118] to 54 min [40–76; P < 0.001]. Secondary outcomes also improved, including door-to-thrombolysis time (90 min [68–114] vs. 68.5 min [54–90]; P < 0.001) and proportion of patients thrombolysed (11 vs. 16%; P < 0.001). The proportion of patients transferred for thrombectomy was unchanged (6 vs. 7%; P = 0.69). Seventy VR sessions totaling 15 h 39 min of training time were logged. VR training usage varied across sites (3–31 sessions per site).ConclusionsDelivery of a multi-factorial intervention including infrastructure, funding, education and training (with VR workflow training) as part of a state-wide telestroke rollout was associated with improved acute stroke treatment metrics. Additional work is required to identify the contribution of each intervention component on clinical outcomes and to increase training uptake and sustainment.
Published: 2024
Full Text: View/download PDF

3. Movable typing of full‐lumen personalized Vein‐Chips to model cerebral venous sinus thrombosis

Author: Yunduo Charles Zhao, Yingqi Zhang, Arian Nasser, Tianbo Hong, Zihao Wang, Allan Sun, Laura Moldovan, Leon S Edwards, Freda Passam, Ken S Butcher, Timothy Ang, and Lining Arnold Ju
Subjects: 3D printing, cerebral venous sinus thrombosis, mechanobiology, Organ on chip, platelet, Virchow's triad, Chemistry, QD1-999, Biology (General), QH301-705.5
Abstract: Abstract Cerebral venous sinus thrombosis (CVST) is a type of stroke associated with COVID‐19 vaccine‐induced immune thrombotic thrombocytopenia. The precise etiology of CVST often remains elusive due to the highly heterogeneous nature of its governing mechanisms, specifically, Virchow's triad that involves altered blood flow, endothelial dysfunction, and hypercoagulability, which varies substantially amongst individuals. Existing diagnostic and monitoring approaches lack the capability to reflect the combination of these patient‐specific thrombotic determinants. In response to this challenge, we introduce a Vein‐Chip platform that recapitulates the CVST vascular anatomy from magnetic resonance venography and the associated hemodynamic flow profile using the “Chinese Movable Type‐like” soft stereolithography technique. The resultant full‐lumen personalized Vein‐Chips, functionalized with endothelial cells, enable in‐vitro thrombosis assays that can elucidate distinct thrombogenic scenarios between normal vascular conditions and those of endothelial dysfunction. The former displayed minimal platelet aggregation and negligible fibrin deposition, while the latter presented significant fibrin extrusion from platelet aggregations. The low‐cost movable typing technique further enhances the potential for commercialization and broader utilization of personalized Vein‐Chips in surgical labs and at‐home monitoring. Future research and development in this direction will pave the way for improved management and prevention of CVST, ultimately benefiting both patients and healthcare systems.
Published: 2023
Full Text: View/download PDF

4. Microvasculature‐on‐a‐Post Chip That Recapitulates Prothrombotic Vascular Geometries and 3D Flow Disturbance

Author: Yingqi Zhang, San‐Seint‐Seint Aye, Vivian Cheng, Arian Nasser, Tianbo Hong, Parham Vatankhah, Fengtao Jiang, Yunduo Charles Zhao, Laura Moldovan, Allan Sun, Alexander Dupuy, Yao Wang, Zhiyong Li, Timothy Ang, Freda Passam, Ken‐Tye Yong, and Lining Arnold Ju
Subjects: flow disturbance, mechanobiology, microfluidics, Stenosis, thrombosis, Physics, QC1-999, Technology
Abstract: Abstract Stenosis, characterized by partial vessel narrowing, alters blood hemodynamics and can lead to unpredictable thrombosis. Existing models struggle to accurately represent the complex vascular geometries and hemodynamics involved in such conditions. To address this challenge, a microvasculature‐on‐a‐post chip is developed to mimic partially stenotic vascular geometries and thrombogenicity, featuring isolated 3D micropost structures with variable sizes that recreate disturbed flow profiles. To emulate the diseased vessel wall, the post microfluidics are vascularized with a confluent layer of endothelial cells. Subsequently, human blood is perfused through the endothelialized post microfluidics, observing the temporal and spatial thrombotic response governed by Virchow's triad, including vessel wall injury, hemodynamic disturbance, and hypercoagulability. The innovative model offers valuable insights into stenosis‐induced thrombosis and endothelial behavior, paving the way for improved assessment of thrombotic risks associated with stenotic vessels. This advanced microfluidic platform also offers new approaches for evaluation of prothrombotic phenotypes and cardiovascular risk assessment in the future.
Published: 2023
Full Text: View/download PDF

5. Telestroke Assessment With Perfusion CT Improves the Diagnostic Accuracy of Stroke vs. Mimic

Author: Lucinda Tran, Longting Lin, Neil Spratt, Andrew Bivard, Beng Lim Alvin Chew, James W. Evans, William O'Brien, Christopher Levi, Timothy Ang, Khaled Alanati, Elizabeth Pepper, Carlos Garcia-Esperon, and Mark Parsons
Subjects: stroke, telestroke, imaging—computed tomography, transient ischaemic attack (TIA), CT perfusion (CTP), stroke mimic, Neurology. Diseases of the nervous system, RC346-429
Abstract: Background and Purpose: CT perfusion (CTP) has been implemented widely in regional areas of Australia for telestroke assessment. The aim of this study was to determine if, as part of telestroke assessment, CTP provided added benefit to clinical features in distinguishing between strokes and mimic and between transient ischaemic attack (TIA) and mimic.Methods: We retrospectively analysed 1,513 consecutively recruited patients referred to the Northern New South Wales Telestroke service, where CTP is performed as a part of telestroke assessment. Patients were classified based on the final diagnosis of stroke, TIA, or mimic. Multivariate regression models were used to determine factors that could be used to differentiate between stroke and mimic and between TIA and mimic.Results: There were 693 strokes, 97 TIA, and 259 mimics included in the multivariate regression models. For the stroke vs. mimic model using symptoms only, the area under the curve (AUC) on the receiver operator curve (ROC) was 0.71 (95% CI 0.67–0.75). For the stroke vs. mimic model using the absence of ischaemic lesion on CTP in addition to clinical features, the AUC was 0.90 (95% CI 0.88–0.92). The multivariate regression model for predicting mimic from TIA using symptoms produced an AUC of 0.71 (95% CI 0.65–0.76). The addition of absence of an ischaemic lesion on CTP to clinical features for the TIA vs. mimic model had an AUC of 0.78 (95% CI 0.73–0.83)Conclusions: In the telehealth setting, the absence of an ischaemic lesion on CTP adds to the diagnostic accuracy in distinguishing mimic from stroke, above that from clinical features.
Published: 2021
Full Text: View/download PDF

6. Endovascular Thrombectomy for Ischemic Stroke Increases Disability-Free Survival, Quality of Life, and Life Expectancy and Reduces Cost

Author: Bruce C. V. Campbell, Peter J. Mitchell, Leonid Churilov, Mahsa Keshtkaran, Keun-Sik Hong, Timothy J. Kleinig, Helen M. Dewey, Nawaf Yassi, Bernard Yan, Richard J. Dowling, Mark W. Parsons, Teddy Y. Wu, Mark Brooks, Marion A. Simpson, Ferdinand Miteff, Christopher R. Levi, Martin Krause, Timothy J. Harrington, Kenneth C. Faulder, Brendan S. Steinfort, Timothy Ang, Rebecca Scroop, P. Alan Barber, Ben McGuinness, Tissa Wijeratne, Thanh G. Phan, Winston Chong, Ronil V. Chandra, Christopher F. Bladin, Henry Rice, Laetitia de Villiers, Henry Ma, Patricia M. Desmond, Atte Meretoja, Dominique A. Cadilhac, Geoffrey A. Donnan, Stephen M. Davis, on behalf of the EXTEND-IA Investigators, Stephen M Davis, Geoffrey A Donnan, Bruce CV Campbell, Peter J Mitchell, Richard Dowling, Thomas J Oxley, Teddy Y Wu, Gabriel Silver, Amy McDonald, Rachael McCoy, Timothy J Kleinig, Helen M Dewey, Marion Simpson, Bronwyn Coulton, Timothy J Harrington, Brendan Steinfort, Kenneth Faulder, Miriam Priglinger, Susan Day, Thanh Phan, Michael Holt, Ronil V Chandra, Dennis Young, Kitty Wong, Hans Tu, Elizabeth Mackay, Sherisse Celestino, Christopher F Bladin, Poh Sien Loh, Amanda Gilligan, Zofia Ross, Skye Coote, Tanya Frost, Mark W Parsons, Christopher R Levi, Neil Spratt, Lara Kaauwai, Monica Badve, Ayton Hope, Maurice Moriarty, Patricia Bennett, Andrew Wong, Alan Coulthard, Andrew Lee, Jim Jannes, Deborah Field, Gagan Sharma, Simon Salinas, Elise Cowley, Barry Snow, John Kolbe, Richard Stark, John King, Richard Macdonnell, John Attia, and Cate D’Este
Subjects: ischemic stroke, thrombolysis, endovascular therapy, mechanical thrombectomy, intraarterial therapy, Solitaire stent retriever device, Neurology. Diseases of the nervous system, RC346-429
Abstract: BackgroundEndovascular thrombectomy improves functional outcome in large vessel occlusion ischemic stroke. We examined disability, quality of life, survival and acute care costs in the EXTEND-IA trial, which used CT-perfusion imaging selection.MethodsLarge vessel ischemic stroke patients with favorable CT-perfusion were randomized to endovascular thrombectomy after alteplase versus alteplase-only. Clinical outcome was prospectively measured using 90-day modified Rankin scale (mRS). Individual patient expected survival and net difference in Disability/Quality-adjusted life years (DALY/QALY) up to 15 years from stroke were modeled using age, sex, 90-day mRS, and utility scores. Level of care within the first 90 days was prospectively measured and used to estimate procedure and inpatient care costs (US$ reference year 2014).ResultsThere were 70 patients, 35 in each arm, mean age 69, median NIHSS 15 (IQR 12–19). The median (IQR) disability-weighted utility score at 90 days was 0.65 (0.00–0.91) in the alteplase-only versus 0.91 (0.65–1.00) in the endovascular group (p = 0.005). Modeled life expectancy was greater in the endovascular versus alteplase-only group (median 15.6 versus 11.2 years, p = 0.02). The endovascular thrombectomy group had fewer simulated DALYs lost over 15 years [median (IQR) 5.5 (3.2–8.7) versus 8.9 (4.7–13.8), p = 0.02] and more QALY gained [median (IQR) 9.3 (4.2–13.1) versus 4.9 (0.3–8.5), p = 0.03]. Endovascular patients spent less time in hospital [median (IQR) 5 (3–11) days versus 8 (5–14) days, p = 0.04] and rehabilitation [median (IQR) 0 (0–28) versus 27 (0–65) days, p = 0.03]. The estimated inpatient costs in the first 90 days were less in the thrombectomy group (average US$15,689 versus US$30,569, p = 0.008) offsetting the costs of interhospital transport and the thrombectomy procedure (average US$10,515). The average saving per patient treated with thrombectomy was US$4,365.ConclusionThrombectomy patients with large vessel occlusion and salvageable tissue on CT-perfusion had reduced length of stay and overall costs to 90 days. There was evidence of clinically relevant improvement in long-term survival and quality of life.Clinical Trial Registrationhttp://www.ClinicalTrials.gov NCT01492725 (registered 20/11/2011).
Published: 2017
Full Text: View/download PDF

7. Tenecteplase Treatment and Thrombus Characteristics Associated With Early Reperfusion: An EXTEND-IA TNK Trials Analysis

Author: Vignan Yogendrakumar, Leonid Churilov, Prodipta Guha, James Beharry, Peter J. Mitchell, Timothy J. Kleinig, Nawaf Yassi, Vincent Thijs, Teddy Y. Wu, Helen Brown, Helen M. Dewey, Tissa Wijeratne, Bernard Yan, Gagan Sharma, Patricia M. Desmond, Mark W. Parsons, Geoffrey A. Donnan, Stephen M. Davis, Bruce C.V. Campbell, Richard Dowling, Steven Bush, Rebecca Scroop, Mark Brooks, Hamed Asadi, Timothy Ang, Ferdinand Miteff, Christopher Levi, Henry Zhao, Felix Ng, Fana Alemseged, Henry Rice, Laetitia de Villiers, Kendal Redmond, and David Leggett
Subjects: Advanced and Specialized Nursing, Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract: Background: Intracranial occlusion site, contrast permeability, and clot burden are thrombus characteristics that influence alteplase-associated reperfusion. In this study, we assessed the reperfusion efficacy of tenecteplase and alteplase in subgroups based on these characteristics in a pooled analysis of the EXTEND-IA TNK trial (Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke). Methods: Patients with large vessel occlusion were randomized to treatment with tenecteplase (0.25 or 0.4 mg/kg) or alteplase before thrombectomy in hospitals across Australia and New Zealand (2015–2019). The primary outcome, early reperfusion, was defined as the absence of retrievable thrombus or >50% reperfusion on first-pass angiogram. We compared the effect of tenecteplase versus alteplase overall, and in subgroups, based on the following measured with computed tomography angiography: intracranial occlusion site, contrast permeability (measured via residual flow grades), and clot burden (measured via clot burden scores). We adjusted for covariates using mixed effects logistic regression models. Results: Tenecteplase was associated with higher odds of early reperfusion (75/369 [20%] versus alteplase: 9/96 [9%], adjusted odds ratio [aOR], 2.18 [95% CI, 1.03–4.63]). The difference between thrombolytics was notable in occlusions with low clot burden (tenecteplase: 66/261 [25%] versus alteplase: 5/67 [7%], aOR, 3.93 [95% CI, 1.50–10.33]) when compared to high clot burden lesions (tenecteplase: 9/108 [8%] versus alteplase: 4/29 [14%], aOR, 0.58 [95% CI, 0.16–2.06]; P interaction =0.01). We did not observe an association between contrast permeability and tenecteplase treatment effect (permeability present: aOR, 2.83 [95% CI, 1.00–8.05] versus absent: aOR, 1.98 [95% CI, 0.65–6.03]; P interaction =0.62). Tenecteplase treatment effect was superior with distal M1 or M2 occlusions (53/176 [30%] versus alteplase: 4/42 [10%], aOR, 3.73 [95% CI, 1.25–11.11]), but both thrombolytics had limited efficacy with internal carotid artery occlusions (tenecteplase 1/73 [1%] versus alteplase 1/19 [5%], aOR, 0.22 [95% CI, 0.01–3.83]; P interaction =0.16). Conclusions: Tenecteplase demonstrates superior early reperfusion versus alteplase in lesions with low clot burden. Reperfusion efficacy remains limited in internal carotid artery occlusions and lesions with high clot burden. Further innovation in thrombolytic therapies are required.
Published: 2023

8. Ultra-Long Transfers for Endovascular Thrombectomy—Mission Impossible?: The Australia-New Zealand Experience

Author: Carlos Garcia-Esperon, Teddy Y. Wu, Vinicius Carraro do Nascimento, Bernard Yan, Craig Kurunawai, Tim Kleinig, Gregory Selkirk, David Blacker, P. Alan Barber, Annemarei Ranta, Alvaro Cervera, Andrew Wong, Peter Mitchell, Claire Muller, Hal Rice, Laetitia De Villiers, Jim Jannes, Jae Beom Hong, Peter Bailey, Helen Brown, Bruce C.V. Campbell, Duncan Wilson, John Fink, Timothy Ang, Christopher Bladin, Tim Phillips, Md Golam Hasnain, Kenneth Butcher, Ferdinand Miteff, Christopher R. Levi, Neil J. Spratt, Mark W. Parsons, Beng Lim Alvin Chew, Mary Morgan, Wayne Collecutt, Martin Krauss, Aaron Tan, Joshua Mahadevan, Matthew Willcourt, and Andrew Bivard
Subjects: Stroke, Advanced and Specialized Nursing, Treatment Outcome, Endovascular Procedures, Humans, Neurology (clinical), Middle Aged, Cardiology and Cardiovascular Medicine, Brain Ischemia, Retrospective Studies, New Zealand, Thrombectomy
Abstract: Background: Endovascular thrombectomy (EVT) access in remote areas is limited. Preliminary data suggest that long distance transfers for EVT may be beneficial; however, the magnitude and best imaging strategy at the referring center remains uncertain. We hypothesized that patients transferred >300 miles would benefit from EVT, achieving rates of functional independence (modified Rankin Scale [mRS] score of 0–2) at 3 months similar to those patients treated at the comprehensive stroke center in the randomized EVT extended window trials and that the selection of patients with computed tomography perfusion (CTP) at the referring site would be associated with ordinal shift toward better outcomes on the mRS. Methods: This is a retrospective analysis of patients transferred from 31 referring hospitals >300 miles (measured by the most direct road distance) to 9 comprehensive stroke centers in Australia and New Zealand for EVT consideration (April 2016 through May 2021). Results: There were 131 patients; the median age was 64 [53–74] years and the median baseline National Institutes of Health Stroke Scale score was 16 [12–22]. At baseline, 79 patients (60.3%) had noncontrast CT+CT angiography, 52 (39.7%) also had CTP. At the comprehensive stroke center, 114 (87%) patients underwent cerebral angiography, and 96 (73.3%) proceeded to EVT. At 3 months, 62 patients (48.4%) had an mRS score of 0 to 2 and 81 (63.3%) mRS score of 0 to 3. CTP selection at the referring site was not associated with better ordinal scores on the mRS at 3 months (mRS median of 2 [1–3] versus 3 [1–6] in the patients selected with noncontrast CT+CT angiography, P =0.1). Nevertheless, patients selected with CTP were less likely to have an mRS score of 5 to 6 (odds ratio 0.03 [0.01–0.19]; P Conclusions: In selected patients transferred >300 miles, there was a benefit for EVT, with outcomes similar to those treated in the comprehensive stroke center in the EVT extended window trials. Remote hospital CTP selection was not associated with ordinal mRS improvement, but was associated with fewer very poor 3-month outcomes.
Published: 2023

9. Novel Movable Typing for Personalized Vein‐Chips in Large Scale: Recapitulate Patient‐Specific Virchow's Triad and its Contribution to Cerebral Venous Sinus Thrombosis

Author: Yunduo Charles Zhao, Yingqi Zhang, Zihao Wang, Fengtao Jiang, Kiarash Kyanian, San‐Seint‐Seint Aye, Tianbo Hong, Parham Vatankhah, Arian Nasser, Allan Sun, Laura Moldovan, Qian P. Su, Ann‐Na Cho, Yao Wang, Freda Passam, Timothy Ang, and Lining Arnold Ju
Subjects: Biomaterials, Electrochemistry, Condensed Matter Physics, Electronic, Optical and Magnetic Materials
Published: 2023

10. Optic nerve sheath fenestration for treating papilloedema in the era of cerebral venous sinus stenting

Author: Peter J. McCluskey, Danny Lam, Timothy Ang, Michael J. Todd, and Gábor M. Halmágyi
Subjects: Ophthalmology
Published: 2023

11. Thrombectomy Improves Outcomes in Paediatric Large Vessel Occlusion Stroke: A Case-Control Study

Author: Kartik Bhatia, Samyami Chowdhury, Ian Andrews, Robert Goetti, Richard Webster, Christopher Troedson, Russell C. Dale, Prakash Muthusami, Carmen Parra Farinas, Nomazulu Dlamini, Mahendra Moharir, Christina Miteff, Ferdinand Miteff, John Worthington, Kylie Tastula, Timothy Ang, Romain Briest, and Elizabeth Pulcine
Published: 2023

12. Transverse Sinus Stenting Reverses Medically Refractory Idiopathic Intracranial Hypertension

Author: Kate Reid, H. Stephen Winters, Timothy Ang, Geoffrey D. Parker, and G. Michael Halmagyi
Abstract: AimTo characterise the ophthalmic indications for, and ophthalmic efficacy of, transverse sinus stenting in adults with medically refractory idiopathic intracranial hypertension.MethodsA retrospective cohort study was undertaken on a single-author database of 226 successive patients with confirmed idiopathic intracranial hypertension (IIH). A total of 32 patients were identified who received a transverse sinus stent for medically refractory disease. This which was defined as visual threat and/or intolerance of maximal medical therapy. Patients with medically refractory disease proceeded to stenting, if found to have a significant transverse sinus stenosis gradient at catheter venography. Visual threat was quantified via the degree of papilledema on optical coherence tomography of the retinal nerve fibre layer, and via the visual field mean deviation. CSF opening pressure at lumbar puncture and cerebral venous sinus pressure measurements from catheter venography were correlated with the ophthalmic data, noting also intolerance of maximal medical therapy. Complications of stenting were fully assessed.ResultsMedically refractory IIH was found in 18% of the total cohort of IIH patients. 90% of those with medically refractory disease had a significant transverse sinus stenosis pressure gradient, and 80% proceeded to stenting. The intervention eliminated papilledema in 96% of stented patients, and allowed 81% to cease acetazolamide. The need for a further procedure was low at 6%, and the safety profile was favourable.ConclusionsMedically refractory disease in IIH is common (18%), and nearly always associated with a significant transverse sinus stenosis pressure gradient (90%). Endovascular stenting of the stenosis deserves wider uptake as a highly effective, safe, and usually definitive treatment. It safeguards vision by eliminating papilledema (96%), and allows most patients to cease acetazolamide (81%). By analogy with glaucoma, if acetazolamide is the prostaglandin of IIH and CSF diversion the emergency glaucoma filter, stenting is the minimally invasive glaucoma surgery.
Published: 2022

13. Diagnostic Utility of Computed Tomography Perfusion in the Telestroke Setting

Author: Kshitij Arora, Aaron Gaekwad, James Evans, William O’Brien, Timothy Ang, Carlos Garcia-Esperon, Christopher Blair, Leon S. Edwards, Beng L.A. Chew, Candice Delcourt, Neil J. Spratt, Mark W. Parsons, and Ken S. Butcher
Subjects: Advanced and Specialized Nursing, Perfusion, Stroke, Humans, Neurology (clinical), Cardiology and Cardiovascular Medicine, Tomography, X-Ray Computed, Brain Ischemia, Cerebral Angiography, Ischemic Stroke
Abstract: Background: Definitive diagnosis of acute ischemic stroke is challenging, particularly in telestroke settings. Although the prognostic utility of CT perfusion (CTP) has been questioned, its diagnostic value remains under-appreciated, especially in cases without an easily visible intracranial occlusion. We assessed the diagnostic accuracy of routine CTP in the acute telestroke setting. Methods: Acute and follow-up data collected prospectively from consecutive suspected patients with stroke assessed by a state-wide telestroke service between March 2020 and August 2021 at 12 sites in Australia were analyzed. All patients in the final analysis had been assessed with multimodal CT, including CTP, which was post-processed with automated volumetric software. Diagnostic sensitivity and specificity were calculated for multimodal CT and each individual component (noncontrast CT [NCCT], CT angiogram [CTA], and CTP). Final diagnosis determined by consensus review of follow-up imaging and clinical data was used as the reference standard. Results: During the study period, complete multimodal CT examination was obtained in 831 patients, 457 of whom were diagnosed with stroke. Diagnostic sensitivity for ischemic stroke increased by 19.5 percentage points when CTP was included with NCCT and CTA compared with NCCT and CTA alone (73.1% positive with NCCT+CTA+CTP [95% CI, 68.8–77.1] versus 53.6% positive with NCCT+CTA alone [95% CI, 48.9–58.3], P P =0.13). Multimodal CT, including CTP, demonstrated the highest negative predictive value (75.0% [95% CI, 72.1–77.7]). Patients with stroke not evident on CTP had small volume infarcts on follow-up (1.2 mL, interquartile range 0.5–2.7mL). Conclusions: Acquisition of CTP as part of a telestroke imaging protocol permits definitive diagnosis of cerebral ischemia in 1 in 5 patients with normal NCCT and CTA.
Published: 2022

14. Incidence and Natural History of Pediatric Large Vessel Occlusion Stroke: A Population Study

Author: Kartik D. Bhatia, Romain Briest, Robert Goetti, Richard Webster, Christopher Troedson, Russell C. Dale, Prakash Muthusami, Christina Miteff, Ferdinand Miteff, John Worthington, Kylie Tastula, Timothy Ang, and Ian Andrews
Subjects: Male, Incidence, Arterial Occlusive Diseases, Brain Ischemia, Cohort Studies, Stroke, Treatment Outcome, Humans, Female, Neurology (clinical), Child, Original Investigation, Ischemic Stroke, Retrospective Studies, Thrombectomy
Abstract: IMPORTANCE: The incidence and natural history of large vessel occlusion (LVO) stroke in children is largely unknown. These knowledge gaps limit the uptake of reperfusion therapies and reduce the efficiency of pediatric acute stroke pathways. OBJECTIVE: To determine the incidence and natural history of pediatric LVO stroke. DESIGN, SETTING, AND PARTICIPANTS: This retrospective population-based cohort study was conducted between January 2010 and December 2019, with a mean (SD) follow-up of 37.0 (28.8) months. Admissions from all pediatric hospitals in the state of New South Wales, Australia, with a final diagnosis of arterial ischemic stroke (AIS) in patients 1 month to younger than 17 years were included. A total of 85 of 251 identified cases were excluded based on selection criteria. Data were analyzed from July 2020 to June 2021. EXPOSURES: One-third of patients with LVO received mechanical thrombectomy with or without intravenous thrombolysis while the remainder were treated conservatively. MAIN OUTCOMES AND MEASURES: The primary outcome was the pediatric modified Rankin Scale (ped-mRS) score 3 months after stroke. Ordinal logistic regression was used to compare non-LVO, LVO without thrombectomy, and LVO with thrombectomy groups. RESULTS: Of 161 included patients, 56 (34.8%) were female, and the mean (SD) age was 6.1 (5.4) years. A total of 166 AIS admissions were studied, and clinical follow-up was available for 164 of 166 admissions. LVO was present in 39 admissions (23.5%). The incidence of LVO stroke was 0.24 per 100 000 patients per year (95% CI, 0.13-0.35). Patients with LVO who did not receive thrombectomy (n = 26) had poor neurological outcomes, with 19 (73.1%) experiencing moderate to severe disability or death (ped-mRS score of 3 to 6) at 3 months (6 of 12 patients receiving thrombectomy [50.0%]; 25 of 38 patients with LVO [65.8%]). Patients with LVO without thrombectomy had significantly worse clinical outcomes than patients with non-LVO at 3 months (odds ratio, 3.64; 95% CI, 1.68-7.87; P = .001). Most patients with LVO presented within time windows suitable for thrombectomy (27 of 39 [69.2%] within 6 hours; 35 of 39 [89.7%] within 24 hours). CONCLUSIONS AND RELEVANCE: In this population-based cohort study, the natural history of pediatric patients with LVO stroke treated conservatively was poor, with most experiencing lifelong disability or death. Nearly 90% of pediatric patients with LVO presented within time windows suitable for thrombectomy.
Published: 2022

15. 029 High Sensitivity Troponin in Acute Ischaemic Stroke Study (TACIS)

Author: John M. Worthington, Michael Hayes, Andrew Hannaford, Nimalin Harinesan, and Timothy Ang
Subjects: medicine.medical_specialty, biology, business.industry, Confounding, Renal function, medicine.disease, Troponin, Internal medicine, High sensitivity troponin, Diabetes mellitus, Ischaemic stroke, medicine, Cardiology, biology.protein, business, Prospective cohort study, Stroke
Abstract: Objective We designed a multi-centre prospective cohort study to explore the hypothesis that early acutely elevated high sensitivity troponin (hsT) is associated with cardioembolic stroke (CES) Methods Ischaemic strokes across three hospitals underwent hsTroponin testing and 2 blinded clinicians classified patients as CES, NCE (Non Cardioembolic) or ESUS by ESUS criteria. Characteristics included baseline NIHSS, renal function, hypertension, diabetes, smoking, ischaemic heart disease, past stroke and congestive cardiac failure. The odds of positive hsT for CES Vs NCE and ESUS Vs NCE were modelled with step-wise addition of patient characteristics. Results 194 ischaemic stroke cases were included, with a mean age of 71 years and a 57:43 male:female ratio. 65 had a positive hsTroponin, which was associated with older age, hypertension, cardiac failure, coronary disease, an eGFR Conclusions An elevated hs troponin after acute ischaemic stroke is independently associated with a cardioembolic mechanism. High sensitivity cardiac troponin was not significantly associated with ESUS after adjusting for confounders, suggesting that a cardio-embolic cause may not be the dominant mechanism in this group.
Published: 2021

16. Current perspectives on neuroimaging techniques used to identify stroke mimics in clinical practice

Author: Shadi El-Wahsh, Timothy Ang, Sophie Dunkerton, Candice Delcourt, and Hugh Stephen Winters
Subjects: medicine.medical_specialty, business.industry, General Neuroscience, Stroke mimics, Neuroimaging, medicine.disease, Magnetic Resonance Imaging, 030227 psychiatry, Brain Ischemia, Clinical Practice, Stroke, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Reperfusion, medicine, Humans, Pharmacology (medical), cardiovascular diseases, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Urgent clinical assessment and brain imaging are essential for differentiating stroke mimics from stroke and to avoid unnecessary initiation of reperfusion and other therapies in stroke mimic patients.In this article, the authors will review acute stroke imaging and then the imaging patterns of the most common stroke mimics. The authors have focused our review on brain CT scan, and more specifically CT perfusion, as this is the most commonly available and emerging tool in emergency settings. The authors also provide information on acute brain MRI and MR perfusion.Imaging can contribute to the detection and diagnosis of acute stroke mimics. Knowledge of imaging findings in different stroke mimics can help distinguish these from patients with stroke who require timely reperfusion therapy. CT and MRI perfusion and diffusion-weighted imaging (DWI) MRI are useful imaging modalities for the assessment of acute stroke patients as they provide more accurate information than plain CT scan. Some of these modalities should be available in the emergency setting. The authors recommended CT perfusion as a useful tool for stroke management and differentiation with stroke mimics.
Published: 2021

17. Tenecteplase versus alteplase before endovascular thrombectomy (EXTEND-IA TNK): A multicenter, randomized, controlled study

Author: Richard Dowling, Peter Barber, Mark Brooks, Bill O'Brien, Vincent Thijs, Laetitia de Villiers, Teddy Y. Wu, Neil Mahant, Alan Coulthard, Patricia Desmond, Marion Simpson, Mark W Parsons, Stephen M. Davis, Peter L. Bailey, Geoffrey A. Donnan, Bruce C.V. Campbell, Ben McGuinness, Hamed Asadi, Christopher F. Bladin, Rebecca Scroop, Ferdinand Miteff, David Leggett, Tissa Wijeratne, Extend-Ia Tnk Investigators, Leonid Churilov, Kendal Redmond, Bernard Yan, Timothy Ang, Martin Krause, Brendan Steinfort, Helen Brown, Timothy Harrington, Wayne Collecutt, Anoop Madan, Ronil V. Chandra, Darshan Shah, Henry Ma, Timothy Kleinig, Peter Mitchell, Winston Chong, Henry Rice, Geoffrey Parker, Helen M Dewey, John Worthington, Kenneth Faulder, Nawaf Yassi, Deborah Field, Steven Bush, Christopher R Levi, Geoffrey Cloud, and Andrew Wong
Subjects: Adult, Male, medicine.medical_specialty, Tomography Scanners, X-Ray Computed, Adolescent, medicine.medical_treatment, Tenecteplase, 030204 cardiovascular system & hematology, Tissue plasminogen activator, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Fibrinolytic Agents, Modified Rankin Scale, Internal medicine, medicine, Humans, Stroke, Aged, Thrombectomy, Aged, 80 and over, Intracerebral hemorrhage, business.industry, Cerebral infarction, Endovascular Procedures, Australia, Thrombolysis, Middle Aged, medicine.disease, Treatment Outcome, Neurology, Tissue Plasminogen Activator, Cardiology, Female, business, 030217 neurology & neurosurgery, Fibrinolytic agent, New Zealand, medicine.drug
Abstract: Background and hypothesis Intravenous thrombolysis with alteplase remains standard care prior to thrombectomy for eligible patients within 4.5 h of ischemic stroke onset. However, alteplase only succeeds in reperfusing large vessel arterial occlusion prior to thrombectomy in a minority of patients. We hypothesized that tenecteplase is non-inferior to alteplase in achieving reperfusion at initial angiogram, when administered within 4.5 h of ischemic stroke onset, in patients planned to undergo endovascular therapy. Study design EXTEND-IA TNK is an investigator-initiated, phase II, multicenter, prospective, randomized, open-label, blinded-endpoint non-inferiority study. Eligibility requires a diagnosis of ischemic stroke within 4.5 h of stroke onset, pre-stroke modified Rankin Scale≤3 (no upper age limit), large vessel occlusion (internal carotid, basilar, or middle cerebral artery) on multimodal computed tomography and absence of contraindications to intravenous thrombolysis. Patients are randomized to either IV alteplase (0.9 mg/kg, max 90 mg) or tenecteplase (0.25 mg/kg, max 25 mg) prior to thrombectomy. Study outcomes The primary outcome measure is reperfusion on the initial catheter angiogram, assessed as modified treatment in cerebral infarction 2 b/3 or the absence of retrievable thrombus. Secondary outcomes include modified Rankin Scale at day 90 and favorable clinical response (reduction in National Institutes of Health Stroke Scale by ≥8 points or reaching 0–1) at day 3. Safety outcomes are death and symptomatic intracerebral hemorrhage. Trial registration ClinicalTrials.gov NCT02388061
Published: 2017

18. The establishment of a telestroke service using multimodal CT imaging decision assistance: 'Turning on the fog lights'

Author: Jennifer Rudd, Claire Sewell, Mark W Parsons, Andrew Bivard, Christopher R Levi, Carlos Garcia-Esperon, Jelle Demeestere, Longting Lin, James Wills, Timothy Ang, Ferdinand Miteff, Neil J. Spratt, Louise Jordan, and Venkatesh Krishnamurthy
Subjects: Male, Telemedicine, medicine.medical_treatment, Clinical Decision-Making, Perfusion scanning, Multimodal Imaging, Brain Ischemia, 03 medical and health sciences, 0302 clinical medicine, Fibrinolytic Agents, Physiology (medical), Humans, Medicine, Thrombolytic Therapy, 030212 general & internal medicine, Stroke, Aged, Service (business), Multimodal imaging, business.industry, Patient Selection, Australia, General Medicine, Thrombolysis, Middle Aged, medicine.disease, Multimodal ct, Neurology, Tissue Plasminogen Activator, Female, Surgery, Neurology (clinical), Medical emergency, Tomography, X-Ray Computed, business, 030217 neurology & neurosurgery, Fibrinolytic agent
Abstract: Telestroke services have been shown to increase stroke therapy access in rural areas. The implementation of advanced CT imaging for patient assessment may improve patient selection and detection of stroke mimics in conjunction with telestroke. We implemented a telestroke service supported by multimodal CT imaging in a rural hospital in Australia. Over 21 months we conducted an evaluation of service activation, thrombolysis rates and use of multimodal imaging to assess the feasibility of the service. Rates of symptomatic intracranial haemorrhage and 90-day modified Rankin Score were used as safety outcomes. Fifty-eight patients were assessed using telestroke, of which 41 were regarded to be acute ischemic strokes and 17 to be stroke mimics on clinical grounds. Of the 41 acute stroke patients, 22 patients were deemed eligible for thrombolysis. Using multimodal CT imaging, 8 more patients were excluded from treatment because of lack of treatment target. Multimodal imaging failed to be obtained in one patient. For the 14 treated patients, median door-imaging time was 38 min. Median door-treatment time was 91 min. A 90-day mRS ⩽2 was achieved in 40% of treated patients. We conclude that a telestroke service using advanced CT imaging for therapy decision assistance can be successfully implemented in regional Australia and can be used to guide acute stroke treatment decision-making and improve access to thrombolytic therapy. Efficiency and safety is comparable to established telestroke services.
Published: 2017

19. Mechanical thrombectomy in pediatric stroke: systematic review, individual patient data meta-analysis, and case series

Author: Kartik Dev Bhatia, Christopher Blair, Geoffrey D. Parker, Timothy Ang, Prakash Muthusami, David Brunacci, Timo Krings, J Mocco, Hans Kortman, Hazem Shoirah, and John M. Worthington
Subjects: Pediatrics, medicine.medical_specialty, business.industry, General Medicine, Publication bias, Patient data, medicine.disease, Mechanical thrombectomy, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Meta-analysis, Medicine, Pediatric stroke, In patient, business, Stroke, 030217 neurology & neurosurgery, Cohort study
Abstract: OBJECTIVEThe role of mechanical thrombectomy in pediatric acute ischemic stroke is uncertain, despite extensive evidence of benefit in adults. The existing literature consists of several recent small single-arm cohort studies, as well as multiple prior small case series and case reports. Published reports of pediatric cases have increased markedly since 2015, after the publication of the positive trials in adults. The recent AHA/ASA Scientific Statement on this issue was informed predominantly by pre-2015 case reports and identified several knowledge gaps, including how young a child may undergo thrombectomy. A repeat systematic review and meta-analysis is warranted to help guide therapeutic decisions and address gaps in knowledge.METHODSUsing PRISMA-IPD guidelines, the authors performed a systematic review of the literature from 1999 to April 2019 and individual patient data meta-analysis, with 2 independent reviewers. An additional series of 3 cases in adolescent males from one of the authors’ centers was also included. The primary outcomes were the rate of good long-term (mRS score 0–2 at final follow-up) and short-term (reduction in NIHSS score by ≥ 8 points or NIHSS score 0–1 at up to 24 hours post-thrombectomy) neurological outcomes following mechanical thrombectomy for acute ischemic stroke in patients < 18 years of age. The secondary outcome was the rate of successful angiographic recanalization (mTICI score 2b/3).RESULTSThe authors’ review yielded 113 cases of mechanical thrombectomy in 110 pediatric patients. Although complete follow-up data are not available for all patients, 87 of 96 (90.6%) had good long-term neurological outcomes (mRS score 0–2), 55 of 79 (69.6%) had good short-term neurological outcomes, and 86 of 98 (87.8%) had successful angiographic recanalization (mTICI score 2b/3). Death occurred in 2 patients and symptomatic intracranial hemorrhage in 1 patient. Sixteen published thrombectomy cases were identified in children < 5 years of age.CONCLUSIONSMechanical thrombectomy may be considered for acute ischemic stroke due to large vessel occlusion (ICA terminus, M1, basilar artery) in patients aged 1–18 years (Level C evidence; Class IIb recommendation). The existing evidence base is likely affected by selection and publication bias. A prospective multinational registry is recommended as the next investigative step.
Published: 2019

20. Extending thrombolysis to 4·5–9 h and wake-up stroke using perfusion imaging. a systematic review and meta-analysis of individual patient data

Author: Bruce C V Campbell, Henry Ma, Peter A Ringleb, Mark W Parsons, Leonid Churilov, Martin Bendszus, Christopher R Levi, Chung Hsu, Timothy J Kleinig, Marc Fatar, Didier Leys, Carlos Molina, Tissa Wijeratne, Sami Curtze, Helen M Dewey, P Alan Barber, Kenneth S Butcher, Deidre A De Silva, Christopher F Bladin, Nawaf Yassi, Johannes A R Pfaff, Gagan Sharma, Andrew Bivard, Patricia M Desmond, Stefan Schwab, Peter D Schellinger, Bernard Yan, Peter J Mitchell, Joaquín Serena, Danilo Toni, Vincent Thijs, Werner Hacke, Stephen M Davis, Geoffrey A Donnan, Geoffrey A. Donnan, Stephen M. Davis, Bruce C.V. Campbell, Mark W. Parsons, Peter J. Mitchell, Patricia M. Desmond, Thomas Oxley, Teddy Y. Wu, Darshan Shah, Henry Zhao, Edrich Rodrigues, Patrick Salvaris, Fana Alemseged, Felix Ng, Cameron Williams, Jo-Lyn Ng, Hans T-H. Tu, Amy McDonald, David Jackson, Jessica Tsoleridis, Rachael McCoy, Lauren Pesavento, Louise Weir, Timothy J. Kleinig, S. Patel, J. Harvey, J. Mahadevan, E. Cheong, Anna Balabanski, Michael Waters, Roy Drew, Jennifer Cranefield, Elizabeth Mackey, Sherisse Celestino, Essie Low, Helen M. Dewey, Christopher F. Bladin, Poh Sien Loh, Philip M. Choi, Skye Coote, Tanya Frost, K. Hogan, C. Ding, S. McModie, W.W. Zhang, Christopher Kyndt, A. Moore, Z. Ross, J. Liu, Ferdinand Miteff, Christopher R. Levi, Timothy Ang, Neil Spratt, Carlos Garcia-Esperon, Lara Kaauwai, Thanh G. Phan, John Ly, Shaloo Singhal, Benjamin Clissold, Kitty Wong, Martin Krause, Susan Day, Jonathan Sturm, Bill O'Brian, Rohan Grimley, Marion Simpson, Matthew Lee-Archer, Amy Brodtmann, Bronwyn Coulton, Dennis Young, Andrew A. Wong, Claire Muller, Deborah K. Field, W. Vallat, Vanessa Maxwell, Peter Bailey, Arman Sabet, Sachin Mishra, Meng Tan, K. George, P. Alan Barber, L. Zhao, Atte Meretoja, Turgut Tatlisumak, G. Sibolt, M. Tiainen, M. Koivu, K. Aarnio, J. Virta, O. Kasari, S. Eirola, M.C. Sun, T.C. Chen, C.S. Chuang, Y.Y. Chen, C.M. Lin, S.C. Ho, P.M. Hsiao, C.H. Tsai, W.S. Huang, Y.W. Yang, H.Y. Huang, W.C. Wang, C.H. Liu, M.K. Lu, C.H. Lu, W.L. Kung, S.K. Jiang, Y.H. Wu, S.C. Huang, C.H. Tseng, L.T. Tseng, Y.C. Guo, D. Lin, C.T. Hsu, C.W. Kuan, J.P. Hsu, H.T. Tsai, M. Suzuki, Y. Sun, H.F. Chen, C.J. Lu, C.H. Lin, C.C. Huang, H.J. Chu, C.Y. Lee, W.H. Chang, Y.C. Lo, Y.T. Hsu, C.H. Chen, P.S. Sung, C.L. Ysai, J.S. Jeng, S.C. Tang, L.K. Tsai, S.J. Yeh, Y.C. Lee, Y.T. Wang, T.C. Chung, C.J. Hu, L. Chan, Y.W. Chiou, L.M. Lien, H.L. Yeh, J.H. Yeh, W.H. Chen, C.L. Lau, A. Chang, I.Y. Lee, M.Y. Huang, J.T. Lee, G.S. Peng, J.C. Lim, Y.D. Hsu, C.C. Lin, C.A. Cheng, C.H. Yen, F.C. Yang, C.H. Hsu, Y.F. Sung, C.K. Tsai, C.L. Tsai, A. Lee, Graeme Hankey, David Blacker, Richard Gerraty, C-I. Chen, C-S. Hsu, Elise Cowley, Michele Sallaberger, Barry Snow, John Kolbe, Richard Stark, John King, Richard Macdonnell, John Attia, Catherine D'Este, Julie Bernhardt, Leeanne Carey, Dominique Cadilhac, Craig Anderson, David Howells, A. Barber, Alan Connelly, Malcolm Macleod, Victoria O'Collins, W. Wilson, L. Macaulay, Erich Bluhmki, Christoph Eschenfelder, Peter Ringleb, Peter Schellinger, Nils Wahlgren, Joanna Wardlaw, Catherine Oppenheim, Kennedy R. Lees, Markku Kaste, Rüdiger von Kummer, Gilles Chatellier, Rico Laage, Xavier Nuñez, Christina Ehrenkrona, Ann-Sofie Svenson, Lynda Cove, Kurt Niederkorn, Franz Gruber, Peter Kapeller, Robert Mikulik, Jean-Louis Mas, Jörg Berrouschot, Jan Sobesky, Martin Köhrmann, Thorsten Steiner, Christof Kessler, Rainer Dziewas, Sven Poli, Katharina Althaus-Knaurer, Paolo Bovi, Alain L. Rodriguez, Juan F. Arenillas, Keith Muir, Roland Veltkamp, Anand Dixit, Girish Muddegowda, Lalit Kala, Deidre A. De Silva, Kenneth S. Butcher, G. Byrnes, Andre Peeters, J.B. Chalk, John N. Fink, Thomas E. Kimber, David Schultz, Peter J. Hand, Judith Frayne, Brian M. Tress, John McNeil, R. Burns, C. Johnston, and M. Williams
Subjects: medicine.medical_specialty, acute ischemic stroke, thrombolysis, Perfusion Imaging, medicine.medical_treatment, Perfusion scanning, 030204 cardiovascular system & hematology, Placebo, Brain Ischemia, Time-to-Treatment, 03 medical and health sciences, 0302 clinical medicine, Fibrinolytic Agents, Modified Rankin Scale, Internal medicine, medicine, Humans, Thrombolytic Therapy, rt-pa, 030212 general & internal medicine, Stroke, Cerebral Hemorrhage, business.industry, General Medicine, Odds ratio, Thrombolysis, medicine.disease, 3. Good health, meta-analysis, Diffusion Magnetic Resonance Imaging, Treatment Outcome, Tissue Plasminogen Activator, Meta-analysis, acute stroke therapy, Tomography, X-Ray Computed, business, Fibrinolytic agent
Abstract: Stroke thrombolysis with alteplase is currently recommended 0-4·5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4·5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis.In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4·5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036.We identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1·86, 95% CI 1·15-2·99, p=0·011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [1%] of 201 patients in the placebo group; adjusted OR 9·7, 95% CI 1·23-76·55, p=0·031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1·55, 0·81-2·96, p=0·66).Patients with ischaemic stroke 4·5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis.None.
Published: 2019

21. Penumbral imaging and functional outcome in patients with anterior circulation ischaemic stroke treated with endovascular thrombectomy versus medical therapy: a meta-analysis of individual patient-level data

Author: Bruce C V Campbell, Charles B L M Majoie, Gregory W Albers, Bijoy K Menon, Nawaf Yassi, Gagan Sharma, Wim H van Zwam, Robert J van Oostenbrugge, Andrew M Demchuk, Francis Guillemin, Philip White, Antoni Dávalos, Aad van der Lugt, Kenneth S Butcher, Aboubaker Cherifi, Henk A Marquering, Geoffrey Cloud, Juan M Macho Fernández, Jeremy Madigan, Catherine Oppenheim, Geoffrey A Donnan, Yvo B W E M Roos, Jai Shankar, Hester Lingsma, Alain Bonafé, Hélène Raoult, María Hernández-Pérez, Aditya Bharatha, Reza Jahan, Olav Jansen, Sébastien Richard, Elad I Levy, Olvert A Berkhemer, Marc Soudant, Lucia Aja, Stephen M Davis, Timo Krings, Marie Tisserand, Luis San Román, Alejandro Tomasello, Debbie Beumer, Scott Brown, David S Liebeskind, Serge Bracard, Keith W Muir, Diederik W J Dippel, Mayank Goyal, Jeffrey L Saver, Tudor G Jovin, Michael D Hill, Peter J Mitchell, Puck SS Fransen, Lucie A van den Berg, Hester F Lingsma, Albert J Yoo, Wouter J Schonewille, Jan Albert Vos, Paul J Nederkoorn, Marieke JH Wermer, Marianne AA van Walderveen, Julie Staals, Jeannette Hofmeijer, Jacques A. van Oostayen, Geert J. Lycklama à Nijeholt, Jelis Boiten, Patrick A. Brouwer, Bart J. Emmer, Sebastiaan F. de Bruijn, Lukas C. van Dijk, Jaap Kappelle, Rob H Lo, Ewoud J. van Dijk, Joost de Vries, Paul L.M. de Kort, Willem Jan J. van Rooij, Jan S.P. van den Berg, Boudewijn A.A.M. van Hasselt, Leo A.M. Aerden, René J. Dallinga, Marieke C. Visser, Joseph C.J. Bot, Patrick C. Vroomen, Omid Eshghi, Tobien H.C.M.L. Schreuder, Roel J.J. Heijboer, Koos Keizer, Alexander V. Tielbeek, Heleen M. den Hertog, Dick G. Gerrits, Renske M. van den Berg-Vos, Giorgos B. Karas, Ewout W. Steyerberg, Zwenneke Flach, Henk A. Marquering, Marieke E.S. Sprengers, Sjoerd F.M. Jenniskens, Ludo F.M. Beenen, René van den Berg, Peter J. Koudstaal, Wim H. van Zwam, Yvo B.W.E.M. Roos, Robert J. van Oostenbrugge, Charles B.L.M. Majoie, Diederik W.J. Dippel, Martin M. Brown, Thomas Liebig, Theo Stijnen, Tommy Andersson, Heinrich Mattle, Nils Wahlgren, Esther van der Heijden, Naziha Ghannouti, Nadine Fleitour, Imke Hooijenga, Corina Puppels, Wilma Pellikaan, Annet Geerling, Annemieke Lindl-Velema, Gina van Vemde, Ans de Ridder, Paut Greebe, José de Bont-Stikkelbroeck, Joke de Meris, Kirsten Janssen, Willy Struijk, Silvan Licher, Nikki Boodt, Adriaan Ros, Esmee Venema, Ilse Slokkers, Raymie-Jayce Ganpat, Maxim Mulder, Nawid Saiedie, Alis Heshmatollah, Stefanie Schipperen, Stefan Vinken, Tiemen van Boxtel, Jeroen Koets, Merel Boers, Emilie Santos, Jordi Borst, Ivo Jansen, Manon Kappelhof, Marit Lucas, Ralph Geuskens, Renan Sales Barros, Roeland Dobbe, Marloes Csizmadia, MD Hill, M Goyal, AM Demchuk, BK Menon, M Eesa, KJ Ryckborst, MR Wright, NR Kamal, L Andersen, PA Randhawa, T Stewart, S Patil, P Minhas, M Almekhlafi, S Mishra, F Clement, T Sajobi, A Shuaib, WJ Montanera, D Roy, FL Silver, TG Jovin, DF Frei, B Sapkota, JL Rempel, J Thornton, D Williams, D Tampieri, AY Poppe, D Dowlatshahi, JH Wong, AP Mitha, S Subramaniam, G Hull, MW Lowerison, M Salluzzi, M Maxwell, S Lacusta, E Drupals, K Armitage, PA Barber, EE Smith, WF Morrish, SB Coutts, C Derdeyn, B Demaerschalk, D Yavagal, R Martin, R Brant, Y Yu, RA Willinsky, A Weill, C Kenney, H Aram, PK Stys, TW Watson, G Klein, D Pearson, P Couillard, A Trivedi, D Singh, E Klourfeld, O Imoukhuede, D Nikneshan, S Blayney, R Reddy, P Choi, M Horton, T Musuka, V Dubuc, TS Field, J Desai, S Adatia, A Alseraya, V Nambiar, R van Dijk, NJ Newcommon, B Schwindt, KS Butcher, T Jeerakathil, B Buck, K Khan, SS Naik, DJ Emery, RJ Owen, TB Kotylak, RA Ashforth, TA Yeo, D McNally, M Siddiqui, M Saqqur, D Hussain, H Kalashyan, A Manosalva, M Kate, L Gioia, S Hasan, A Mohammad, M Muratoglu, A Cullen, P Brennan, A O'Hare, S Looby, D Hyland, S Duff, M McCusker, B Hallinan, S Lee, J McCormack, A Moore, M O'Connor, C Donegan, L Brewer, A Martin, S Murphy, K O'Rourke, S Smyth, P Kelly, T Lynch, T Daly, P O'Brien, A O'Driscoll, M Martin, R Collins, T Coughlan, D McCabe, D O'Neill, M Mulroy, O Lynch, T Walsh, M O'Donnell, T Galvin, J Harbison, P McElwaine, K Mulpeter, C McLoughlin, M Reardon, E Harkin, E Dolan, M Watts, N Cunningham, C Fallon, S Gallagher, P Cotter, M Crowe, R Doyle, I Noone, M Lapierre, VA Coté, S Lanthier, C Odier, A Durocher, J Raymond, N Daneault, Y Deschaintre, B Jankowitz, L Baxendell, L Massaro, C Jackson-Graves, S Decesare, P Porter, K Armbruster, A Adams, J Billigan, J Oakley, A Ducruet, A Jadhav, D-V Giurgiutiu, A Aghaebrahim, V Reddy, M Hammer, M Starr, V Totoraitis, L Wechsler, S Streib, S Rangaraju, D Campbell, M Rocha, D Gulati, T Krings, L Kalman, A Cayley, J Williams, R Wiegner, LK Casaubon, C Jaigobin, JM del Campo, E Elamin, JD Schaafsma, R Agid, R Farb, K ter Brugge, BL Sapkoda, BW Baxter, K Barton, A Knox, A Porter, A Sirelkhatim, T Devlin, C Dellinger, N Pitiyanuvath, J Patterson, J Nichols, S Quarfordt, J Calvert, H Hawk, C Fanale, A Bitner, A Novak, D Huddle, R Bellon, D Loy, J Wagner, I Chang, E Lampe, B Spencer, R Pratt, R Bartt, S Shine, G Dooley, T Nguyen, M Whaley, K McCarthy, J Teitelbaum, W Poon, N Campbell, M Cortes, C Lum, R Shamloul, S Robert, G Stotts, M Shamy, N Steffenhagen, D Blacquiere, M Hogan, M AlHazzaa, G Basir, H Lesiuk, D Iancu, M Santos, H Choe, DC Weisman, K Jonczak, A Blue-Schaller, Q Shah, L MacKenzie, B Klein, K Kulandaivel, O Kozak, DJ Gzesh, LJ Harris, JS Khoury, J Mandzia, D Pelz, S Crann, L Fleming, K Hesser, B Beauchamp, B Amato-Marzialli, M Boulton, P Lopez- Ojeda, M Sharma, S Lownie, R Chan, R Swartz, P Howard, D Golob, D Gladstone, K Boyle, M Boulos, J Hopyan, V Yang, L Da Costa, CA Holmstedt, AS Turk, R Navarro, E Jauch, S Ozark, R Turner, S Phillips, J Shankar, J Jarrett, G Gubitz, W Maloney, R Vandorpe, M Schmidt, J Heidenreich, G Hunter, M Kelly, R Whelan, L Peeling, PA Burns, A Hunter, I Wiggam, E Kerr, M Watt, A Fulton, P Gordon, I Rennie, P Flynn, G Smyth, S O'Leary, N Gentile, G Linares, P McNelis, K Erkmen, P Katz, A Azizi, M Weaver, C Jungreis, S Faro, P Shah, H Reimer, V Kalugdan, G Saposnik, A Bharatha, Y Li, P Kostyrko, T Marotta, W Montanera, D Sarma, D Selchen, J Spears, JH Heo, K Jeong, DJ Kim, BM Kim, YD Kim, D Song, K-J Lee, J Yoo, OY Bang, S Rho, J Lee, P Jeon, KH Kim, J Cha, SJ Kim, S Ryoo, MJ Lee, S-I Sohn, C-H Kim, H-G Ryu, J-H Hong, H-W Chang, C-Y Lee, J Rha, Bruce CV Campbell, Leonid Churilov, Bernard Yan, Richard Dowling, Thomas J Oxley, Teddy Y Wu, Gabriel Silver, Amy McDonald, Rachael McCoy, Timothy J Kleinig, Rebecca Scroop, Helen M Dewey, Marion Simpson, Mark Brooks, Bronwyn Coulton, Martin Krause, Timothy J Harrington, Brendan Steinfort, Kenneth Faulder, Miriam Priglinger, Susan Day, Thanh Phan, Winston Chong, Michael Holt, Ronil V Chandra, Henry Ma, Dennis Young, Kitty Wong, Tissa Wijeratne, Hans Tu, Elizabeth Mackay, Sherisse Celestino, Christopher F Bladin, Poh Sien Loh, Amanda Gilligan, Zofia Ross, Skye Coote, Tanya Frost, Mark W Parsons, Ferdinand Miteff, Christopher R Levi, Timothy Ang, Neil Spratt, Lara Kaauwai, Monica Badve, Henry Rice, Laetitia de Villiers, P. Alan Barber, Ben McGuinness, Ayton Hope, Maurice Moriarty, Patricia Bennett, Andrew Wong, Alan Coulthard, Andrew Lee, Jim Jannes, Deborah Field, Simon Salinas, Elise Cowley, Barry Snow, John Kolbe, Richard Stark, John King, Richard Macdonnell, John Attia, Cate D'Este, Hans-Christoph Diener, Elad I. Levy, Vitor Mendes Pereira, Gregory W. Albers, Christophe Cognard, David J. Cohen, Werner Hacke, Tudor G. Jovin, Heinrich P. Mattle, Raul G. Nogueira, Adnan H. Siddiqui, Dileep R. Yavagal, Rüdiger von Kummer, Wade Smith, Francis Turjman, Scott Hamilton, Richard Chiacchierini, Arun Amar, Nerses Sanossian, Yince Loh, B Baxter, VK Reddy, A Horev, M Star, A Siddiqui, LN Hopkins, K Snyder, R Sawyer, S Hall, V Costalat, C Riquelme, P Machi, E Omer, C Arquizan, I Mourand, M Charif, X Ayrignac, N Menjot de Champfleur, N Leboucq, G Gascou, M Moynier, R du Mesnil de Rochemont, O Singer, J Berkefeld, C Foerch, M Lorenz, W Pfeilschifer, E Hattingen, M Wagner, SJ You, S Lescher, H Braun, S Dehkharghani, SR Belagaje, A Anderson, A Lima, M Obideen, D Haussen, R Dharia, M Frankel, V Patel, K Owada, A Saad, L Amerson, C Horn, S Doppelheuer, K Schindler, DK Lopes, M Chen, R Moftakhar, C Anton, M Smreczak, JS Carpenter, S Boo, A Rai, T Roberts, A Tarabishy, L Gutmann, C Brooks, J Brick, J Domico, G Reimann, K Hinrichs, M Becker, E Heiss, C Selle, A Witteler, S Al-Boutros, M-J Danch, A Ranft, S Rohde, K Burg, C Weimar, V Zegarac, C Hartmann, M Schlamann, S Göricke, A Ringlestein, I Wanke, C Mönninghoff, M Dietzold, R Budzik, T Davis, G Eubank, WJ Hicks, P Pema, N Vora, J Mejilla, M Taylor, W Clark, A Rontal, J Fields, B Peterson, G Nesbit, H Lutsep, H Bozorgchami, R Priest, O Ologuntoye, S Barnwell, A Dogan, K Herrick, C Takahasi, N Beadell, B Brown, S Jamieson, MS Hussain, A Russman, F Hui, D Wisco, K Uchino, Z Khawaja, I Katzan, G Toth, E Cheng-Ching, M Bain, S Man, A Farrag, P George, S John, L Shankar, A Drofa, R Dahlgren, A Bauer, A Itreat, A Taqui, R Cerejo, A Richmond, P Ringleb, M Bendszus, M Möhlenbruch, T Reiff, H Amiri, J Purrucker, C Herweh, M Pham, O Menn, I Ludwig, I Acosta, C Villar, W Morgan, C Sombutmai, F Hellinger, E Allen, M Bellew, R Gandhi, E Bonwit, J Aly, RD Ecker, D Seder, J Morris, M Skaletsky, J Belden, C Baker, LS Connolly, P Papanagiotou, C Roth, A Kastrup, M Politi, F Brunner, M Alexandrou, H Merdivan, C Ramsey, C Given II, S Renfrow, V Deshmukh, K Sasadeusz, F Vincent, JT Thiesing, J Putnam, A Bhatt, A Kansara, D Caceves, T Lowenkopf, L Yanase, J Zurasky, S Dancer, B Freeman, T Scheibe-Mirek, J Robison, J Roll, D Clark, M Rodriguez, B-FM Fitzsimmons, O Zaidat, JR Lynch, M Lazzaro, T Larson, L Padmore, E Das, A Farrow-Schmidt, A Hassan, W Tekle, C Cate, O Jansen, C Cnyrim, F Wodarg, C Wiese, A Binder, C Riedel, A Rohr, N Lang, H Laufs, S Krieter, L Remonda, M Diepers, J Añon, K Nedeltchev, T Kahles, S Biethahn, M Lindner, V Chang, C Gächter, C Esperon, M Guglielmetti, JF Arenillas Lara, M Martínez Galdámez, AI Calleja Sanz, E Cortijo Garcia, P Garcia Bermejo, S Perez, P Mulero Carrillo, E Crespo Vallejo, M Ruiz Piñero, L Lopez Mesonero, FJ Reyes Muñoz, C Brekenfeld, J-H Buhk, A Krützelmann, G Thomalla, B Cheng, C Beck, J Hoppe, E Goebell, B Holst, U Grzyska, G Wortmann, S Starkman, G Duckwiler, R Jahan, N Rao, S Sheth, K Ng, A Noorian, V Szeder, M Nour, M McManus, J Huang, J Tarpley, S Tateshima, N Gonzalez, L Ali, D Liebeskind, J Hinman, M Calderon-Arnulphi, C Liang, J Guzy, S Koch, K DeSousa, G Gordon-Perue, M Elhammady, E Peterson, V Pandey, S Dharmadhikari, P Khandelwal, A Malik, R Pafford, P Gonzalez, K Ramdas, G Andersen, D Damgaard, P Von Weitzel-Mudersbach, C Simonsen, N Ruiz de Morales Ayudarte, M Poulsen, L Sørensen, S Karabegovich, M Hjørringgaard, N Hjort, T Harbo, K Sørensen, E Deshaies, D Padalino, A Swarnkar, JG Latorre, E Elnour, Z El-Zammar, M Villwock, H Farid, A Balgude, L Cross, K Hansen, M Holtmannspötter, D Kondziella, J Hoejgaard, S Taudorf, H Soendergaard, A Wagner, M Cronquist, T Stavngaard, M Cortsen, LH Krarup, T Hyldal, H-P Haring, S Guggenberger, M Hamberger, J Trenkler, M Sonnberger, K Nussbaumer, C Dominger, E Bach, BD Jagadeesan, R Taylor, J Kim, K Shea, R Tummala, H Zacharatos, D Sandhu, M Ezzeddine, A Grande, D Hildebrandt, K Miller, J Scherber, A Hendrickson, M Jumaa, S Zaidi, T Hendrickson, V Snyder, M Killer-Oberpfalzer, J Mutzenbach, F Weymayr, E Broussalis, K Stadler, A Jedlitschka, A Malek, N Mueller-Kronast, P Beck, C Martin, D Summers, J Day, I Bettinger, W Holloway, K Olds, S Arkin, N Akhtar, C Boutwell, S Crandall, M Schwartzman, C Weinstein, B Brion, S Prothmann, J Kleine, K Kreiser, T Boeckh-Behrens, H Poppert, S Wunderlich, ML Koch, V Biberacher, A Huberle, G Gora-Stahlberg, B Knier, T Meindl, D Utpadel-Fischler, M Zech, M Kowarik, C Seifert, B Schwaiger, A Puri, S Hou, A Wakhloo, M Moonis, N Henninger, R Goddeau, F Massari, A Minaeian, JD Lozano, M Ramzan, C Stout, A Patel, A Tunguturi, S Onteddu, R Carandang, M Howk, M Ribó, E Sanjuan, M Rubiera, J Pagola, A Flores, M Muchada, P Meler, E Huerga, S Gelabert, P Coscojuela, A Tomasello, D Rodriguez, E Santamarina, O Maisterra, S Boned, L Seró, A Rovira, CA Molina, M Millán, L Muñoz, N Pérez de la Ossa, M Gomis, L Dorado, E López-Cancio, E Palomeras, J Munuera, P García Bermejo, S Remollo, C Castaño, R García-Sort, P Cuadras, P Puyalto, M Hernández-Pérez, M Jiménez, A Martínez-Piñeiro, G Lucente, A Dávalos, A Chamorro, X Urra, V Obach, A Cervera, S Amaro, L Llull, J Codas, M Balasa, J Navarro, H Ariño, A Aceituno, S Rudilosso, A Renu, JM Macho, L San Roman, J Blasco, A López, N Macías, P Cardona, H Quesada, F Rubio, L Cano, B Lara, MA de Miquel, L Aja, J Serena, E Cobo, Kennedy R Lees, J Arenillas, R Roberts, F Al-Ajlan, L Zimmel, S Patel, J Martí-Fàbregas, M Salvat-Plana, S Bracard, Xavier Ducrocq, René Anxionnat, Pierre-Alexandre Baillot, Charlotte Barbier, Anne-Laure Derelle, Jean-Christophe Lacour, Yves Samson, Nader Sourour, Flore Baronnet-Chauvet, Frédéric Clarencon, Sophie Crozier, Sandrine Deltour, Federico Di Maria, Raphael Le Bouc, Anne Leger, Gurkan Mutlu, Charlotte Rosso, Zoltan Szatmary, Marion Yger, Chiara Zavanone, Serge Bakchine, Laurent Pierot, Nathalie Caucheteux, Laurent Estrade, Krzysztof Kadziolka, Alexandre Leautaud, Céline Renkes, Isabelle Serre, Hubert Desal, Benoît Guillon, Claire Boutoleau-Bretonniere, Benjamin Daumas-Duport, Solène De Gaalon, Pascal Derkinderen, Sarah Evain, Fanny Herisson, David-Axel Laplaud, Thibaud Lebouvier, Alina Lintia-Gaultier, Hélène Pouclet-Courtemanche, Tiphaine Rouaud, Violaine Rouaud Jaffrenou, Aurélia Schunck, Mathieu Sevin-Allouet, Frederique Toulgoat, Sandrine Wiertlewski, Jean-Yves Gauvrit, Thomas Ronziere, Vincent Cahagne, Jean-Christophe Ferre, Jean-François Pinel, Jean-Louis Mas, Jean-François Meder, Amen-Adam Al Najjar-Carpentier, Julia Birchenall, Eric Bodiguel, David Calvet, Valérie Domigo, Sylvie Godon-Hardy, Vincent Guiraud, Catherine Lamy, Loubna Majhadi, Ludovic Morin, Olivier Naggara, Denis Trystram, Guillaume Turc, Jérôme Berge, Igor Sibon, Patrice Menegon, Xavier Barreau, François Rouanet, Sabrina Debruxelles, Annabelle Kazadi, Pauline Renou, Olivier Fleury, Anne Pasco-Papon, Frédéric Dubas, Jildaz Caroff, Sophie Godard Ducceschi, Marie-Aurélie Hamon, Alderic Lecluse, Guillaume Marc, Maurice Giroud, Frédéric Ricolfi, Yannick Bejot, Adrien Chavent, Arnaud Gentil, Apolline Kazemi, Guy-Victor Osseby, Charlotte Voguet, Marie-Hélène Mahagne, Jacques Sedat, Yves Chau, Laurent Suissa, Sylvain Lachaud, Emmanuel Houdart, Christian Stapf, Frédérique Buffon Porcher, Hugues Chabriat, Pierre Guedin, Dominique Herve, Eric Jouvent, Jérôme Mawet, Jean-Pierre Saint-Maurice, Hans-Martin Schneble, Norbert Nighoghossian, Nadia-Nawel Berhoune, Françoise Bouhour, Tae-Hee Cho, Laurent Derex, Sandra Felix, Hélène Gervais-Bernard, Benjamin Gory, Luis Manera, Laura Mechtouff, Thomas Ritzenthaler, Roberto Riva, Fabrizio Salaris Silvio, Caroline Tilikete, Raphael Blanc, Michaël Obadia, Mario Bruno Bartolini, Antoine Gueguen, Michel Piotin, Silvia Pistocchi, Hocine Redjem, Jacques Drouineau, Jean-Philippe Neau, Gaelle Godeneche, Matthias Lamy, Emilia Marsac, Stephane Velasco, Pierre Clavelou, Emmanuel Chabert, Nathalie Bourgois, Catherine Cornut-Chauvinc, Anna Ferrier, Jean Gabrillargues, Betty Jean, Anna-Raquel Marques, Nicolas Vitello, Olivier Detante, Marianne Barbieux, Kamel Boubagra, Isabelle Favre Wiki, Katia Garambois, Florence Tahon, Vasdev Ashok, Oguzhan Coskun, Georges Rodesch, Bertrand Lapergue, Frédéric Bourdain, Serge Evrard, Philippe Graveleau, Jean Pierre Decroix, Adrien Wang, François Sellal, Guido Ahle, Gabriela Carelli, Marie-Hélène Dugay, Claude Gaultier, Ariel Pablo Lebedinsky, Lavinia Lita, Raul Mariano Musacchio, Catherine Renglewicz-Destuynder, Alain Tournade, Françis Vuillemet, Francisco Macian Montoro, Charbel Mounayer, Frederic Faugeras, Laetitia Gimenez, Catherine Labach, Géraldine Lautrette, Christian Denier, Guillaume Saliou, Olivier Chassin, Claire Dussaule, Elsa Melki, Augustin Ozanne, Francesco Puccinelli, Marina Sachet, Mariana Sarov, Jean-François Bonneville, Thierry Moulin, Alessandra Biondi, Elisabeth De Bustos Medeiros, Fabrice Vuillier, Patrick Courtheoux, Fausto Viader, Marion Apoil-Brissard, Mathieu Bataille, Anne-Laure Bonnet, Julien Cogez, Emmanuel Touze, Xavier Leclerc, Didier Leys, Mohamed Aggour, Pierre Aguettaz, Marie Bodenant, Charlotte Cordonnier, Dominique Deplanque, Marie Girot, Hilde Henon, Erwah Kalsoum, Christian Lucas, Jean-Pierre Pruvo, Paolo Zuniga, Caroline Arquizan, Vincent Costalat, Paolo Machi, Isabelle Mourand, Carlos Riquelme, Pierre Bounolleau, Charles Arteaga, Anthony Faivre, Marc Bintner, Patrice Tournebize, Cyril Charlin, Françoise Darcel, Pascale Gauthier-Lasalarie, Marcia Jeremenko, Servane Mouton, Jean-Baptiste Zerlauth, Chantal Lamy, Deramond Hervé, Hosseini Hassan, André Gaston, Francis-Guy Barral, Pierre Garnier, Rémy Beaujeux, Valérie Wolff, Denis Herbreteau, Séverine Debiais, Alicia Murray, Gary Ford, Andy Clifton, Janet Freeman, Ian Ford, Hugh Markus, Joanna Wardlaw, Andy Molyneux, Thompson Robinson, Steff Lewis, John Norrie, Fergus Robertson, Richard Perry, Anand Dixit, Andrew Clifton, Christine Roffe, Sanjeev Nayak, Kyriakos Lobotesis, Craig Smith, Amit Herwadkar, Naga Kandasamy, Tony Goddard, John Bamford, Ganesh Subramanian, Rob Lenthall, Edward Littleton, Sal Lamin, Kelley Storey, Rita Ghatala, Azra Banaras, John Aeron-Thomas, Bath Hazel, Holly Maguire, Emelda Veraque, Louise Harrison, Rekha Keshvara, James Cunningham, Clinical Neurophysiology, Weimar, Christian (Beitragende*r), Radiology and nuclear medicine, Rheumatology, ACS - Atherosclerosis & ischemic syndromes, RS: Carim - B05 Cerebral small vessel disease, RS: CARIM - R3.03 - Cerebral small vessel disease, RS: Carim - B06 Imaging, Beeldvorming, MUMC+: DA BV Medisch Specialisten Radiologie (9), RS: CARIM - R3.11 - Imaging, MUMC+: MA Neurologie (3), Klinische Neurowetenschappen, MUMC+: MA AIOS Neurologie (9), The Royal Melbourne Hospital, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Stanford University, University of Calgary, The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University [Maastricht], Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute of Neuroscience [Newcastle] (ION), Newcastle University [Newcastle], Universitat Autònoma de Barcelona (UAB), Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Alberta, Centre d'Investigation Clinique - Innovation Technologique [Nancy] (CIC-IT), Monash University [Melbourne], St George’s University Hospitals, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Dalhousie University [Halifax], Neuroradiologie [Hôpital Gui de Chauliac], Hôpital Gui de Chauliac [Montpellier], Service de Neuroradiologie [Rennes], CHU Pontchaillou [Rennes], St. Michael's Hospital, University of California [Los Angeles] (UCLA), University of California, University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), Kiel University, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), University at Buffalo [SUNY] (SUNY Buffalo), State University of New York (SUNY), Toronto Western Hospital, Hôpital Foch [Suresnes], Vall d'Hebron University Hospital [Barcelona], Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), University of Glasgow, Queen Elizabeth University Hospital (Glasgow), David Geffen School of Medicine [Los Angeles], University of California-University of California, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Radiology & Nuclear Medicine, Public Health, Neurology, Radiology and Nuclear Medicine, ACS - Microcirculation, ANS - Neurovascular Disorders, ACS - Amsterdam Cardiovascular Sciences, Graduate School, ACS - Pulmonary hypertension & thrombosis, AGEM - Digestive immunity, AGEM - Re-generation and cancer of the digestive system, ARD - Amsterdam Reproduction and Development, Biomedical Engineering and Physics, APH - Personalized Medicine, APH - Quality of Care, and AMS - Restoration & Development
Subjects: SELECTION, COMPUTED TOMOGRAPHIC PERFUSION, Medizin, Perfusion scanning, 030204 cardiovascular system & hematology, Brain Ischemia, 0302 clinical medicine, Modified Rankin Scale, REPERFUSION, Stroke, ComputingMilieux_MISCELLANEOUS, Thrombectomy, Aged, 80 and over, medicine.diagnostic_test, Penumbra, Endovascular Procedures, Brain, Middle Aged, Magnetic Resonance Imaging, 3. Good health, Treatment Outcome, Cerebral blood flow, Tissue Plasminogen Activator, INFARCT, Cardiology, Female, TRIAL, CT, medicine.medical_specialty, Perfusion Imaging, Neuroimaging, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 03 medical and health sciences, Fibrinolytic Agents, ALTEPLASE, Internal medicine, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Aged, business.industry, MECHANICAL THROMBECTOMY, Other Research Radboud Institute for Health Sciences [Radboudumc 0], Magnetic resonance imaging, Odds ratio, medicine.disease, Neurology (clinical), business, Tomography, X-Ray Computed, 030217 neurology & neurosurgery, Fibrinolytic agent, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background CT perfusion (CTP) and diffusion or perfusion MRI might assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of irreversibly injured ischaemic core and potentially salvageable penumbra volumes were associated with functional outcome and whether they interacted with the treatment effect of endovascular thrombectomy on functional outcome.Methods In this systematic review and meta-analysis, the HERMES collaboration pooled patient-level data from all randomised controlled trials that compared endovascular thrombectomy (predominantly using stent retrievers) with standard medical therapy in patients with anterior circulation ischaemic stroke, published in PubMed from Jan 1,2010, to May 31, 2017. The primary endpoint was functional outcome, assessed by the modified Rankin Scale (mRS) at 90 days after stroke. Ischaemic core was estimated, before treatment with either endovascular thrombectomy or standard medical therapy, by CTP as relative cerebral blood flow less than 30% of normal brain blood flow or by MRI as an apparent diffusion coefficient less than 620 mu m(2)/s. Critically hypoperfused tissue was estimated as the volume of tissue with a CTP time to maximum longer than 6 s. Mismatch volume (ie, the estimated penumbral volume) was calculated as critically hypoperfused tissue volume minus ischaemic core volume. The association of ischaemic core and penumbral volumes with 90-day mRS score was analysed with multivariable logistic regression (functional independence, defined as mRS score 0-2) and ordinal logistic regression (functional improvement by at least one mRS category) in all patients and in a subset of those with more than 50% endovascular reperfusion, adjusted for baseline prognostic variables. The meta-analysis was prospectively designed by the HERMES executive committee, but not registered.Findings We identified seven studies with 1764 patients, all of which were included in the meta-analysis. CTP was available and assessable for 591 (34%) patients and diffusion MRI for 309 (18%) patients. Functional independence was worse in patients who had CTP versus those who had diffusion MRI, after adjustment for ischaemic core volume (odds ratio [OR] 0.47 [95% CI 0.30-0.72], p=0.0007), so the imaging modalities were not pooled. Increasing ischaemic core volume was associated with reduced likelihood of functional independence (CTP OR 0.77 [0.69-0.86] per 10 mL, p(interaction)=0.29; diffusion MRI OR 0.87 [0.81-0.94] per 10 mL, p(interaction)=0.94). Mismatch volume, examined only in the CTP group because of the small numbers of patients who had perfusion MRI, was not associated with either functional independence or functional improvement. In patients with CTP with more than 50% endovascular reperfusion (n=186), age, ischaemic core volume, and imaging-to-reperfusion time were independently associated with functional improvement. Risk of bias between studies was generally low.Interpretation Estimated ischaemic core volume was independently associated with functional independence and functional improvement but did not modify the treatment benefit of endovascular thrombectomy over standard medical therapy for improved functional outcome. Combining ischaemic core volume with age and expected imagingto-reperfusion time will improve assessment of prognosis and might inform endovascular thrombectomy treatment decisions. Copyright (C) 2018 Elsevier Ltd. All rights reserved.
Published: 2019

22. Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke

Author: Teddy Y. Wu, Martin Krause, Mark W Parsons, Peter L. Bailey, Carlos Garcia-Esperon, Patrick Salvaris, Henry E. Rice, Steven Bush, Christopher F. Bladin, Winston Chong, Hamed Asadi, Tissa Wijeratne, Richard Dowling, Rebecca Scroop, Nawaf Yassi, Darshan Shah, Christopher R Levi, Mark Brooks, Kendal Redmond, Deborah Field, Helen M Dewey, David Leggett, John Clouston, Vincent Thijs, Ken Mitchell, Stephen M. Davis, Bernard Yan, Henry Zhao, Alan Coulthard, Kate Mahady, Claire Muller, Timothy Ang, Bruce C.V. Campbell, Geoffrey A. Donnan, Wayne Collecutt, Ronil V. Chandra, Kenneth Faulder, John N. Fink, Timothy Kleinig, Thanh G. Phan, Laetitia de Villiers, Andrew Wong, Patricia Desmond, Marion Simpson, Gagan Sharma, Ferdinand Miteff, Leonid Churilov, Henry Ma, Peter Mitchell, Edrich Rodrigues, Lee-Anne Slater, Brendan Steinfort, Timothy Harrington, and Helen Brown
Subjects: Male, medicine.medical_specialty, medicine.medical_treatment, Tenecteplase, 030204 cardiovascular system & hematology, Tissue plasminogen activator, Severity of Illness Index, Brain Ischemia, Time-to-Treatment, Brain ischemia, 03 medical and health sciences, 0302 clinical medicine, Fibrinolytic Agents, Modified Rankin Scale, medicine.artery, Internal medicine, medicine, Humans, Single-Blind Method, Myocardial infarction, Aged, Cerebral Hemorrhage, Thrombectomy, Aged, 80 and over, business.industry, Endovascular Procedures, General Medicine, Thrombolysis, Middle Aged, medicine.disease, Combined Modality Therapy, Stroke, Logistic Models, Tissue Plasminogen Activator, Middle cerebral artery, Reperfusion, Cardiology, Female, business, 030217 neurology & neurosurgery, Fibrinolytic agent, medicine.drug
Abstract: Intravenous infusion of alteplase is used for thrombolysis before endovascular thrombectomy for ischemic stroke. Tenecteplase, which is more fibrin-specific and has longer activity than alteplase, is given as a bolus and may increase the incidence of vascular reperfusion.We randomly assigned patients with ischemic stroke who had occlusion of the internal carotid, basilar, or middle cerebral artery and who were eligible to undergo thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or alteplase (at a dose of 0.9 mg per kilogram; maximum dose, 90 mg) within 4.5 hours after symptom onset. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory or an absence of retrievable thrombus at the time of the initial angiographic assessment. Noninferiority of tenecteplase was tested, followed by superiority. Secondary outcomes included the modified Rankin scale score (on a scale from 0 [no neurologic deficit] to 6 [death]) at 90 days. Safety outcomes were death and symptomatic intracerebral hemorrhage.Of 202 patients enrolled, 101 were assigned to receive tenecteplase and 101 to receive alteplase. The primary outcome occurred in 22% of the patients treated with tenecteplase versus 10% of those treated with alteplase (incidence difference, 12 percentage points; 95% confidence interval [CI], 2 to 21; incidence ratio, 2.2; 95% CI, 1.1 to 4.4; P=0.002 for noninferiority; P=0.03 for superiority). Tenecteplase resulted in a better 90-day functional outcome than alteplase (median modified Rankin scale score, 2 vs. 3; common odds ratio, 1.7; 95% CI, 1.0 to 2.8; P=0.04). Symptomatic intracerebral hemorrhage occurred in 1% of the patients in each group.Tenecteplase before thrombectomy was associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours after symptom onset. (Funded by the National Health and Medical Research Council of Australia and others; EXTEND-IA TNK ClinicalTrials.gov number, NCT02388061 .).
Published: 2018

23. Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data

Author: Bruce C V Campbell, Wim H van Zwam, Mayank Goyal, Bijoy K Menon, Diederik W J Dippel, Andrew M Demchuk, Serge Bracard, Philip White, Antoni Dávalos, Charles B L M Majoie, Aad van der Lugt, Gary A Ford, Natalia Pérez de la Ossa, Michael Kelly, Romain Bourcier, Geoffrey A Donnan, Yvo B W E M Roos, Oh Young Bang, Raul G Nogueira, Thomas G Devlin, Lucie A van den Berg, Frédéric Clarençon, Paul Burns, Jeffrey Carpenter, Olvert A Berkhemer, Dileep R Yavagal, Vitor Mendes Pereira, Xavier Ducrocq, Anand Dixit, Helena Quesada, Jonathan Epstein, Stephen M Davis, Olav Jansen, Marta Rubiera, Xabier Urra, Emilien Micard, Hester F Lingsma, Olivier Naggara, Scott Brown, Francis Guillemin, Keith W Muir, Robert J van Oostenbrugge, Jeffrey L Saver, Tudor G Jovin, Michael D Hill, Peter J Mitchell, Puck SS Fransen, Debbie Beumer, Albert J Yoo, Wouter J Schonewille, Jan Albert Vos, Paul J Nederkoorn, Marieke JH Wermer, Marianne AA van Walderveen, Julie Staals, Jeannette Hofmeijer, Jacques A. van Oostayen, Geert J. Lycklama à Nijeholt, Jelis Boiten, Patrick A. Brouwer, Bart J. Emmer, Sebastiaan F. de Bruijn, Lukas C. van Dijk, Jaap Kappelle, Rob H Lo, Ewoud J. van Dijk, Joost de Vries, Paul L.M. de Kort, Willem Jan J. van Rooij, Jan S.P. van den Berg, Boudewijn A.A.M. van Hasselt, Leo A.M. Aerden, René J. Dallinga, Marieke C. Visser, Joseph C.J. Bot, Patrick C. Vroomen, Omid Eshghi, Tobien H.C.M.L. Schreuder, Roel J.J. Heijboer, Koos Keizer, Alexander V. Tielbeek, Heleen M. den Hertog, Dick G. Gerrits, Renske M. van den Berg-Vos, Giorgos B. Karas, Ewout W. Steyerberg, Zwenneke Flach, Henk A. Marquering, Marieke E.S. Sprengers, Sjoerd F.M. Jenniskens, Ludo F.M. Beenen, René van den Berg, Peter J. Koudstaal, Wim H. van Zwam, Yvo B.W.E.M. Roos, Robert J. van Oostenbrugge, Charles B.L.M. Majoie, Diederik W.J. Dippel, Martin M. Brown, Thomas Liebig, Theo Stijnen, Tommy Andersson, Heinrich Mattle, Nils Wahlgren, Esther van der Heijden, Naziha Ghannouti, Nadine Fleitour, Imke Hooijenga, Corina Puppels, Wilma Pellikaan, Annet Geerling, Annemieke Lindl-Velema, Gina van Vemde, Ans de Ridder, Paut Greebe, José de Bont-Stikkelbroeck, Joke de Meris, Kirsten Janssen, Willy Struijk, Silvan Licher, Nikki Boodt, Adriaan Ros, Esmee Venema, Ilse Slokkers, Raymie-Jayce Ganpat, Maxim Mulder, Nawid Saiedie, Alis Heshmatollah, Stefanie Schipperen, Stefan Vinken, Tiemen van Boxtel, Jeroen Koets, Merel Boers, Emilie Santos, Jordi Borst, Ivo Jansen, Manon Kappelhof, Marit Lucas, Ralph Geuskens, Renan Sales Barros, Roeland Dobbe, Marloes Csizmadia, MD Hill, M Goyal, AM Demchuk, BK Menon, M Eesa, KJ Ryckborst, MR Wright, NR Kamal, L Andersen, PA Randhawa, T Stewart, S Patil, P Minhas, M Almekhlafi, S Mishra, F Clement, T Sajobi, A Shuaib, WJ Montanera, D Roy, FL Silver, TG Jovin, DF Frei, B Sapkota, JL Rempel, J Thornton, D Williams, D Tampieri, AY Poppe, D Dowlatshahi, JH Wong, AP Mitha, S Subramaniam, G Hull, MW Lowerison, M Salluzzi, M Maxwell, S Lacusta, E Drupals, K Armitage, PA Barber, EE Smith, WF Morrish, SB Coutts, C Derdeyn, B Demaerschalk, D Yavagal, R Martin, R Brant, Y Yu, RA Willinsky, A Weill, C Kenney, H Aram, PK Stys, TW Watson, G Klein, D Pearson, P Couillard, A Trivedi, D Singh, E Klourfeld, O Imoukhuede, D Nikneshan, S Blayney, R Reddy, P Choi, M Horton, T Musuka, V Dubuc, TS Field, J Desai, S Adatia, A Alseraya, V Nambiar, R van Dijk, NJ Newcommon, B Schwindt, KS Butcher, T Jeerakathil, B Buck, K Khan, SS Naik, DJ Emery, RJ Owen, TB Kotylak, RA Ashforth, TA Yeo, D McNally, M Siddiqui, M Saqqur, D Hussain, H Kalashyan, A Manosalva, M Kate, L Gioia, S Hasan, A Mohammad, M Muratoglu, A Cullen, P Brennan, A O'Hare, S Looby, D Hyland, S Duff, M McCusker, B Hallinan, S Lee, J McCormack, A Moore, M O'Connor, C Donegan, L Brewer, A Martin, S Murphy, K O'Rourke, S Smyth, P Kelly, T Lynch, T Daly, P O'Brien, A O'Driscoll, M Martin, R Collins, T Coughlan, D McCabe, D O'Neill, M Mulroy, O Lynch, T Walsh, M O'Donnell, T Galvin, J Harbison, P McElwaine, K Mulpeter, C McLoughlin, M Reardon, E Harkin, E Dolan, M Watts, N Cunningham, C Fallon, S Gallagher, P Cotter, M Crowe, R Doyle, I Noone, M Lapierre, VA Coté, S Lanthier, C Odier, A Durocher, J Raymond, N Daneault, Y Deschaintre, B Jankowitz, L Baxendell, L Massaro, C Jackson-Graves, S Decesare, P Porter, K Armbruster, A Adams, J Billigan, J Oakley, A Ducruet, A Jadhav, D-V Giurgiutiu, A Aghaebrahim, V Reddy, M Hammer, M Starr, V Totoraitis, L Wechsler, S Streib, S Rangaraju, D Campbell, M Rocha, D Gulati, T Krings, L Kalman, A Cayley, J Williams, R Wiegner, LK Casaubon, C Jaigobin, JM del Campo, E Elamin, JD Schaafsma, R Agid, R Farb, K ter Brugge, BL Sapkoda, BW Baxter, K Barton, A Knox, A Porter, A Sirelkhatim, T Devlin, C Dellinger, N Pitiyanuvath, J Patterson, J Nichols, S Quarfordt, J Calvert, H Hawk, C Fanale, A Bitner, A Novak, D Huddle, R Bellon, D Loy, J Wagner, I Chang, E Lampe, B Spencer, R Pratt, R Bartt, S Shine, G Dooley, T Nguyen, M Whaley, K McCarthy, J Teitelbaum, W Poon, N Campbell, M Cortes, C Lum, R Shamloul, S Robert, G Stotts, M Shamy, N Steffenhagen, D Blacquiere, M Hogan, M AlHazzaa, G Basir, H Lesiuk, D Iancu, M Santos, H Choe, DC Weisman, K Jonczak, A Blue-Schaller, Q Shah, L MacKenzie, B Klein, K Kulandaivel, O Kozak, DJ Gzesh, LJ Harris, JS Khoury, J Mandzia, D Pelz, S Crann, L Fleming, K Hesser, B Beauchamp, B Amato-Marzialli, M Boulton, P Lopez- Ojeda, M Sharma, S Lownie, R Chan, R Swartz, P Howard, D Golob, D Gladstone, K Boyle, M Boulos, J Hopyan, V Yang, L Da Costa, CA Holmstedt, AS Turk, R Navarro, E Jauch, S Ozark, R Turner, S Phillips, J Shankar, J Jarrett, G Gubitz, W Maloney, R Vandorpe, M Schmidt, J Heidenreich, G Hunter, M Kelly, R Whelan, L Peeling, PA Burns, A Hunter, I Wiggam, E Kerr, M Watt, A Fulton, P Gordon, I Rennie, P Flynn, G Smyth, S O'Leary, N Gentile, G Linares, P McNelis, K Erkmen, P Katz, A Azizi, M Weaver, C Jungreis, S Faro, P Shah, H Reimer, V Kalugdan, G Saposnik, A Bharatha, Y Li, P Kostyrko, T Marotta, W Montanera, D Sarma, D Selchen, J Spears, JH Heo, K Jeong, DJ Kim, BM Kim, YD Kim, D Song, K-J Lee, J Yoo, OY Bang, S Rho, J Lee, P Jeon, KH Kim, J Cha, SJ Kim, S Ryoo, MJ Lee, S-I Sohn, C-H Kim, H-G Ryu, J-H Hong, H-W Chang, C-Y Lee, J Rha, Bruce CV Campbell, Leonid Churilov, Bernard Yan, Richard Dowling, Nawaf Yassi, Thomas J Oxley, Teddy Y Wu, Gabriel Silver, Amy McDonald, Rachael McCoy, Timothy J Kleinig, Rebecca Scroop, Helen M Dewey, Marion Simpson, Mark Brooks, Bronwyn Coulton, Martin Krause, Timothy J Harrington, Brendan Steinfort, Kenneth Faulder, Miriam Priglinger, Susan Day, Thanh Phan, Winston Chong, Michael Holt, Ronil V Chandra, Henry Ma, Dennis Young, Kitty Wong, Tissa Wijeratne, Hans Tu, Elizabeth Mackay, Sherisse Celestino, Christopher F Bladin, Poh Sien Loh, Amanda Gilligan, Zofia Ross, Skye Coote, Tanya Frost, Mark W Parsons, Ferdinand Miteff, Christopher R Levi, Timothy Ang, Neil Spratt, Lara Kaauwai, Monica Badve, Henry Rice, Laetitia de Villiers, P. Alan Barber, Ben McGuinness, Ayton Hope, Maurice Moriarty, Patricia Bennett, Andrew Wong, Alan Coulthard, Andrew Lee, Jim Jannes, Deborah Field, Gagan Sharma, Simon Salinas, Elise Cowley, Barry Snow, John Kolbe, Richard Stark, John King, Richard Macdonnell, John Attia, Cate D'Este, Hans-Christoph Diener, Elad I. Levy, Alain Bonafé, Reza Jahan, Gregory W. Albers, Christophe Cognard, David J. Cohen, Werner Hacke, Tudor G. Jovin, Heinrich P. Mattle, Raul G. Nogueira, Adnan H. Siddiqui, Dileep R. Yavagal, Rüdiger von Kummer, Wade Smith, Francis Turjman, Scott Hamilton, Richard Chiacchierini, Arun Amar, Nerses Sanossian, Yince Loh, B Baxter, VK Reddy, A Horev, M Star, A Siddiqui, LN Hopkins, K Snyder, R Sawyer, S Hall, V Costalat, C Riquelme, P Machi, E Omer, C Arquizan, I Mourand, M Charif, X Ayrignac, N Menjot de Champfleur, N Leboucq, G Gascou, M Moynier, R du Mesnil de Rochemont, O Singer, J Berkefeld, C Foerch, M Lorenz, W Pfeilschifer, E Hattingen, M Wagner, SJ You, S Lescher, H Braun, S Dehkharghani, SR Belagaje, A Anderson, A Lima, M Obideen, D Haussen, R Dharia, M Frankel, V Patel, K Owada, A Saad, L Amerson, C Horn, S Doppelheuer, K Schindler, DK Lopes, M Chen, R Moftakhar, C Anton, M Smreczak, JS Carpenter, S Boo, A Rai, T Roberts, A Tarabishy, L Gutmann, C Brooks, J Brick, J Domico, G Reimann, K Hinrichs, M Becker, E Heiss, C Selle, A Witteler, S Al-Boutros, M-J Danch, A Ranft, S Rohde, K Burg, C Weimar, V Zegarac, C Hartmann, M Schlamann, S Göricke, A Ringlestein, I Wanke, C Mönninghoff, M Dietzold, R Budzik, T Davis, G Eubank, WJ Hicks, P Pema, N Vora, J Mejilla, M Taylor, W Clark, A Rontal, J Fields, B Peterson, G Nesbit, H Lutsep, H Bozorgchami, R Priest, O Ologuntoye, S Barnwell, A Dogan, K Herrick, C Takahasi, N Beadell, B Brown, S Jamieson, MS Hussain, A Russman, F Hui, D Wisco, K Uchino, Z Khawaja, I Katzan, G Toth, E Cheng-Ching, M Bain, S Man, A Farrag, P George, S John, L Shankar, A Drofa, R Dahlgren, A Bauer, A Itreat, A Taqui, R Cerejo, A Richmond, P Ringleb, M Bendszus, M Möhlenbruch, T Reiff, H Amiri, J Purrucker, C Herweh, M Pham, O Menn, I Ludwig, I Acosta, C Villar, W Morgan, C Sombutmai, F Hellinger, E Allen, M Bellew, R Gandhi, E Bonwit, J Aly, RD Ecker, D Seder, J Morris, M Skaletsky, J Belden, C Baker, LS Connolly, P Papanagiotou, C Roth, A Kastrup, M Politi, F Brunner, M Alexandrou, H Merdivan, C Ramsey, C Given II, S Renfrow, V Deshmukh, K Sasadeusz, F Vincent, JT Thiesing, J Putnam, A Bhatt, A Kansara, D Caceves, T Lowenkopf, L Yanase, J Zurasky, S Dancer, B Freeman, T Scheibe-Mirek, J Robison, J Roll, D Clark, M Rodriguez, B-FM Fitzsimmons, O Zaidat, JR Lynch, M Lazzaro, T Larson, L Padmore, E Das, A Farrow-Schmidt, A Hassan, W Tekle, C Cate, O Jansen, C Cnyrim, F Wodarg, C Wiese, A Binder, C Riedel, A Rohr, N Lang, H Laufs, S Krieter, L Remonda, M Diepers, J Añon, K Nedeltchev, T Kahles, S Biethahn, M Lindner, V Chang, C Gächter, C Esperon, M Guglielmetti, JF Arenillas Lara, M Martínez Galdámez, AI Calleja Sanz, E Cortijo Garcia, P Garcia Bermejo, S Perez, P Mulero Carrillo, E Crespo Vallejo, M Ruiz Piñero, L Lopez Mesonero, FJ Reyes Muñoz, C Brekenfeld, J-H Buhk, A Krützelmann, G Thomalla, B Cheng, C Beck, J Hoppe, E Goebell, B Holst, U Grzyska, G Wortmann, S Starkman, G Duckwiler, R Jahan, N Rao, S Sheth, K Ng, A Noorian, V Szeder, M Nour, M McManus, J Huang, J Tarpley, S Tateshima, N Gonzalez, L Ali, D Liebeskind, J Hinman, M Calderon-Arnulphi, C Liang, J Guzy, S Koch, K DeSousa, G Gordon-Perue, M Elhammady, E Peterson, V Pandey, S Dharmadhikari, P Khandelwal, A Malik, R Pafford, P Gonzalez, K Ramdas, G Andersen, D Damgaard, P Von Weitzel-Mudersbach, C Simonsen, N Ruiz de Morales Ayudarte, M Poulsen, L Sørensen, S Karabegovich, M Hjørringgaard, N Hjort, T Harbo, K Sørensen, E Deshaies, D Padalino, A Swarnkar, JG Latorre, E Elnour, Z El-Zammar, M Villwock, H Farid, A Balgude, L Cross, K Hansen, M Holtmannspötter, D Kondziella, J Hoejgaard, S Taudorf, H Soendergaard, A Wagner, M Cronquist, T Stavngaard, M Cortsen, LH Krarup, T Hyldal, H-P Haring, S Guggenberger, M Hamberger, J Trenkler, M Sonnberger, K Nussbaumer, C Dominger, E Bach, BD Jagadeesan, R Taylor, J Kim, K Shea, R Tummala, H Zacharatos, D Sandhu, M Ezzeddine, A Grande, D Hildebrandt, K Miller, J Scherber, A Hendrickson, M Jumaa, S Zaidi, T Hendrickson, V Snyder, M Killer-Oberpfalzer, J Mutzenbach, F Weymayr, E Broussalis, K Stadler, A Jedlitschka, A Malek, N Mueller-Kronast, P Beck, C Martin, D Summers, J Day, I Bettinger, W Holloway, K Olds, S Arkin, N Akhtar, C Boutwell, S Crandall, M Schwartzman, C Weinstein, B Brion, S Prothmann, J Kleine, K Kreiser, T Boeckh-Behrens, H Poppert, S Wunderlich, ML Koch, V Biberacher, A Huberle, G Gora-Stahlberg, B Knier, T Meindl, D Utpadel-Fischler, M Zech, M Kowarik, C Seifert, B Schwaiger, A Puri, S Hou, A Wakhloo, M Moonis, N Henninger, R Goddeau, F Massari, A Minaeian, JD Lozano, M Ramzan, C Stout, A Patel, A Tunguturi, S Onteddu, R Carandang, M Howk, M Ribó, E Sanjuan, M Rubiera, J Pagola, A Flores, M Muchada, P Meler, E Huerga, S Gelabert, P Coscojuela, A Tomasello, D Rodriguez, E Santamarina, O Maisterra, S Boned, L Seró, A Rovira, CA Molina, M Millán, L Muñoz, N Pérez de la Ossa, M Gomis, L Dorado, E López-Cancio, E Palomeras, J Munuera, P García Bermejo, S Remollo, C Castaño, R García-Sort, P Cuadras, P Puyalto, M Hernández-Pérez, M Jiménez, A Martínez-Piñeiro, G Lucente, A Dávalos, A Chamorro, X Urra, V Obach, A Cervera, S Amaro, L Llull, J Codas, M Balasa, J Navarro, H Ariño, A Aceituno, S Rudilosso, A Renu, JM Macho, L San Roman, J Blasco, A López, N Macías, P Cardona, H Quesada, F Rubio, L Cano, B Lara, MA de Miquel, L Aja, J Serena, E Cobo, Gregory W Albers, Kennedy R Lees, J Arenillas, R Roberts, F Al-Ajlan, L Zimmel, S Patel, J Martí-Fàbregas, M Salvat-Plana, S Bracard, René Anxionnat, Pierre-Alexandre Baillot, Charlotte Barbier, Anne-Laure Derelle, Jean-Christophe Lacour, Sébastien Richard, Yves Samson, Nader Sourour, Flore Baronnet-Chauvet, Frédéric Clarencon, Sophie Crozier, Sandrine Deltour, Federico Di Maria, Raphael Le Bouc, Anne Leger, Gurkan Mutlu, Charlotte Rosso, Zoltan Szatmary, Marion Yger, Chiara Zavanone, Serge Bakchine, Laurent Pierot, Nathalie Caucheteux, Laurent Estrade, Krzysztof Kadziolka, Alexandre Leautaud, Céline Renkes, Isabelle Serre, Hubert Desal, Benoît Guillon, Claire Boutoleau-Bretonniere, Benjamin Daumas-Duport, Solène De Gaalon, Pascal Derkinderen, Sarah Evain, Fanny Herisson, David-Axel Laplaud, Thibaud Lebouvier, Alina Lintia-Gaultier, Hélène Pouclet-Courtemanche, Tiphaine Rouaud, Violaine Rouaud Jaffrenou, Aurélia Schunck, Mathieu Sevin-Allouet, Frederique Toulgoat, Sandrine Wiertlewski, Jean-Yves Gauvrit, Thomas Ronziere, Vincent Cahagne, Jean-Christophe Ferre, Jean-François Pinel, Hélène Raoult, Jean-Louis Mas, Jean-François Meder, Amen-Adam Al Najjar-Carpentier, Julia Birchenall, Eric Bodiguel, David Calvet, Valérie Domigo, Sylvie Godon-Hardy, Vincent Guiraud, Catherine Lamy, Loubna Majhadi, Ludovic Morin, Denis Trystram, Guillaume Turc, Jérôme Berge, Igor Sibon, Patrice Menegon, Xavier Barreau, François Rouanet, Sabrina Debruxelles, Annabelle Kazadi, Pauline Renou, Olivier Fleury, Anne Pasco-Papon, Frédéric Dubas, Jildaz Caroff, Sophie Godard Ducceschi, Marie-Aurélie Hamon, Alderic Lecluse, Guillaume Marc, Maurice Giroud, Frédéric Ricolfi, Yannick Bejot, Adrien Chavent, Arnaud Gentil, Apolline Kazemi, Guy-Victor Osseby, Charlotte Voguet, Marie-Hélène Mahagne, Jacques Sedat, Yves Chau, Laurent Suissa, Sylvain Lachaud, Emmanuel Houdart, Christian Stapf, Frédérique Buffon Porcher, Hugues Chabriat, Pierre Guedin, Dominique Herve, Eric Jouvent, Jérôme Mawet, Jean-Pierre Saint-Maurice, Hans-Martin Schneble, Norbert Nighoghossian, Nadia-Nawel Berhoune, Françoise Bouhour, Tae-Hee Cho, Laurent Derex, Sandra Felix, Hélène Gervais-Bernard, Benjamin Gory, Luis Manera, Laura Mechtouff, Thomas Ritzenthaler, Roberto Riva, Fabrizio Salaris Silvio, Caroline Tilikete, Raphael Blanc, Michaël Obadia, Mario Bruno Bartolini, Antoine Gueguen, Michel Piotin, Silvia Pistocchi, Hocine Redjem, Jacques Drouineau, Jean-Philippe Neau, Gaelle Godeneche, Matthias Lamy, Emilia Marsac, Stephane Velasco, Pierre Clavelou, Emmanuel Chabert, Nathalie Bourgois, Catherine Cornut-Chauvinc, Anna Ferrier, Jean Gabrillargues, Betty Jean, Anna-Raquel Marques, Nicolas Vitello, Olivier Detante, Marianne Barbieux, Kamel Boubagra, Isabelle Favre Wiki, Katia Garambois, Florence Tahon, Vasdev Ashok, Oguzhan Coskun, Georges Rodesch, Bertrand Lapergue, Frédéric Bourdain, Serge Evrard, Philippe Graveleau, Jean Pierre Decroix, Adrien Wang, François Sellal, Guido Ahle, Gabriela Carelli, Marie-Hélène Dugay, Claude Gaultier, Ariel Pablo Lebedinsky, Lavinia Lita, Raul Mariano Musacchio, Catherine Renglewicz-Destuynder, Alain Tournade, Françis Vuillemet, Francisco Macian Montoro, Charbel Mounayer, Frederic Faugeras, Laetitia Gimenez, Catherine Labach, Géraldine Lautrette, Christian Denier, Guillaume Saliou, Olivier Chassin, Claire Dussaule, Elsa Melki, Augustin Ozanne, Francesco Puccinelli, Marina Sachet, Mariana Sarov, Jean-François Bonneville, Thierry Moulin, Alessandra Biondi, Elisabeth De Bustos Medeiros, Fabrice Vuillier, Patrick Courtheoux, Fausto Viader, Marion Apoil-Brissard, Mathieu Bataille, Anne-Laure Bonnet, Julien Cogez, Emmanuel Touze, Xavier Leclerc, Didier Leys, Mohamed Aggour, Pierre Aguettaz, Marie Bodenant, Charlotte Cordonnier, Dominique Deplanque, Marie Girot, Hilde Henon, Erwah Kalsoum, Christian Lucas, Jean-Pierre Pruvo, Paolo Zuniga, Caroline Arquizan, Vincent Costalat, Paolo Machi, Isabelle Mourand, Carlos Riquelme, Pierre Bounolleau, Charles Arteaga, Anthony Faivre, Marc Bintner, Patrice Tournebize, Cyril Charlin, Françoise Darcel, Pascale Gauthier-Lasalarie, Marcia Jeremenko, Servane Mouton, Jean-Baptiste Zerlauth, Chantal Lamy, Deramond Hervé, Hosseini Hassan, André Gaston, Francis-Guy Barral, Pierre Garnier, Rémy Beaujeux, Valérie Wolff, Denis Herbreteau, Séverine Debiais, Alicia Murray, Gary Ford, Martin M Brown, Andy Clifton, Janet Freeman, Ian Ford, Hugh Markus, Joanna Wardlaw, Andy Molyneux, Thompson Robinson, Steff Lewis, John Norrie, Fergus Robertson, Richard Perry, Geoffrey Cloud, Andrew Clifton, Jeremy Madigan, Christine Roffe, Sanjeev Nayak, Kyriakos Lobotesis, Craig Smith, Amit Herwadkar, Naga Kandasamy, Tony Goddard, John Bamford, Ganesh Subramanian, Rob Lenthall, Edward Littleton, Sal Lamin, Kelley Storey, Rita Ghatala, Azra Banaras, John Aeron-Thomas, Bath Hazel, Holly Maguire, Emelda Veraque, Louise Harrison, Rekha Keshvara, James Cunningham, University of Melbourne, University of Calgary, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), University of Amsterdam [Amsterdam] (UvA), Universitat Autònoma de Barcelona (UAB), Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), ANS - Neurovascular Disorders, Radiology and Nuclear Medicine, ACS - Amsterdam Cardiovascular Sciences, Neurology, Graduate School, Other Research, APH - Personalized Medicine, APH - Quality of Care, Biomedical Engineering and Physics, ARD - Amsterdam Reproduction and Development, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ACS - Microcirculation, ACS - Atherosclerosis & ischemic syndromes, ACS - Pulmonary hypertension & thrombosis, Radiology & Nuclear Medicine, Public Health, Weimar, Christian (Beitragende*r), Molecular cell biology and Immunology, Pathology, Radiology and nuclear medicine, Amsterdam Neuroscience - Neurovascular Disorders, Rheumatology, Beeldvorming, RS: CARIM - R3.03 - Cerebral small vessel disease, RS: CARIM - R3.11 - Imaging, MUMC+: DA BV Medisch Specialisten Radiologie (9), Klinische Neurowetenschappen, and MUMC+: MA Neurologie (3)
Subjects: Male, medicine.medical_specialty, Sedation, Medizin, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 030204 cardiovascular system & hematology, Anesthesia, General, CONTROLLED-TRIAL, THERAPY, law.invention, Brain Ischemia, 03 medical and health sciences, 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, Randomized controlled trial, law, Modified Rankin Scale, Journal Article, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Medicine, Humans, General anaesthesia, Stroke, Aged, Randomized Controlled Trials as Topic, Thrombectomy, Aged, 80 and over, business.industry, Other Research Radboud Institute for Health Sciences [Radboudumc 0], Odds ratio, MR, Middle Aged, Outcome and Process Assessment (Health Care), medicine.disease, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], 3. Good health, Surgery, Outcome and Process Assessment, Health Care, Meta-analysis, Observational study, Female, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Meta-Analysis
Abstract: BACKGROUND: General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care.METHODS: For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered.FINDINGS: Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in patients who had GA (adjusted common odds ratio (cOR) 1·52, 95% CI 1·09-2·11, p=0·014) and in those who did not have GA (adjusted cOR 2·33, 95% CI 1·75-3·10, pINTERPRETATION: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons.FUNDING: Medtronic.
Published: 2018

24. Multi-Modal CT in Acute Stroke: Wait for a Serum Creatinine before Giving Intravenous Contrast? No!

Author: Chung Y. Hsu, Christopher R Levi, Mark W Parsons, B Campbell, Andrew Bivard, Timothy Ang, Stephen M. Davis, Henry Hin Kui Ma, and Geoffrey A. Donnan
Subjects: Male, medicine.medical_specialty, Tomography Scanners, X-Ray Computed, medicine.medical_treatment, Decision Making, Contrast Media, Renal function, Nephropathy, chemistry.chemical_compound, Risk Factors, Internal medicine, medicine, Humans, Saline, Stroke, Aged, Aged, 80 and over, Creatinine, medicine.diagnostic_test, business.industry, Incidence, Brain, Percutaneous coronary intervention, Middle Aged, medicine.disease, Surgery, Radiography, Neurology, chemistry, Angiography, Cardiology, Administration, Intravenous, Female, Kidney Diseases, business, Perfusion, Glomerular Filtration Rate
Abstract: Background Multi-modal CT (MMCT) to guide decision making for reperfusion treatment is increasingly used, but there remains a perceived risk of contrast-induced nephropathy (CIN). At our center, MMCT is used empirically without waiting for serum-creatinine (sCR) or renal profiling. Aims To determine the incidence of CIN, examine the risk factors predisposing to its development, and investigate its effects on clinical outcome in the acute stroke population. Methods An institution-wide protocol was implemented for acute stroke presentations to have MMCT (100–150 ml nonionic tri-iodinated contrast, perfusion CT and CT angiography) without waiting for serum-creatinine to minimize delays. Intravenous saline is routinely infused (80–125 ml/h) for at least 24-h after MMCT. Serial creatinine levels were measured at baseline, risk period, and follow-up. Renal profiles and clinical progress were reviewed up to 90 days. Results We analyzed 735 consecutive patients who had MMCT for the evaluation of acute ischemic or hemorrhagic stroke during the last five-years. A total of 623 patients met the inclusion criteria for analysis: 16 cases (2·6%) biochemically qualified as CIN; however, the risk period serum-creatinine for 15 of these cases was confounded by dehydration, urinary tract infection, or medications. None of the group had progression to chronic kidney disease or required dialysis. Conclusions The incidence of CIN is low when MMCT is used routinely to assess acute stroke patients. In this population, CIN was a biochemical phenomenon that did not have clinical manifestations, cause chronic kidney disease, require dialysis, or negatively impact on 90-day mRS outcomes. Renal profiling and waiting for a baseline serum-creatinine are an unnecessary delay to emergency reperfusion treatment.
Published: 2015

25. Endovascular Therapy for Ischemic Stroke with Perfusion-Imaging Selection

Author: Bruce C.V. Campbell, Peter J. Mitchell, Timothy J. Kleinig, Helen M. Dewey, Leonid Churilov, Nawaf Yassi, Bernard Yan, Richard J. Dowling, Mark W. Parsons, Thomas J. Oxley, Teddy Y. Wu, Mark Brooks, Marion A. Simpson, Ferdinand Miteff, Christopher R. Levi, Martin Krause, Timothy J. Harrington, Kenneth C. Faulder, Brendan S. Steinfort, Miriam Priglinger, Timothy Ang, Rebecca Scroop, P. Alan Barber, Ben McGuinness, Tissa Wijeratne, Thanh G. Phan, Winston Chong, Ronil V. Chandra, Christopher F. Bladin, Monica Badve, Henry Rice, Laetitia de Villiers, Henry Ma, Patricia M. Desmond, Geoffrey A. Donnan, and Stephen M. Davis
Subjects: Intracerebral hemorrhage, medicine.medical_specialty, Solitaire Cryptographic Algorithm, business.industry, medicine.medical_treatment, Perfusion scanning, General Medicine, medicine.disease, Revascularization, Surgery, Brain ischemia, Modified Rankin Scale, Internal medicine, medicine, Cardiology, business, Stroke, Fibrinolytic agent
Abstract: Background Trials of endovascular therapy for ischemic stroke have produced variable results. We conducted this study to test whether more advanced imaging selection, recently developed devices, and earlier intervention improve outcomes. Methods We randomly assigned patients with ischemic stroke who were receiving 0.9 mg of alteplase per kilogram of body weight less than 4.5 hours after the onset of ischemic stroke either to undergo endovascular thrombectomy with the Solitaire FR (Flow Restoration) stent retriever or to continue receiving alteplase alone. All the patients had occlusion of the internal carotid or middle cerebral artery and evidence of salvageable brain tissue and ischemic core of less than 70 ml on computed tomographic (CT) perfusion imaging. The coprimary outcomes were reperfusion at 24 hours and early neurologic improvement (≥8-point reduction on the National Institutes of Health Stroke Scale or a score of 0 or 1 at day 3). Secondary outcomes included the functional score on the modified Rankin scale at 90 days. Results The trial was stopped early because of efficacy after 70 patients had undergone randomization (35 patients in each group). The percentage of ischemic territory that had undergone reperfusion at 24 hours was greater in the endovascular-therapy group than in the alteplase-only group (median, 100% vs. 37%; P
Published: 2015

26. Validation of the National Institutes of Health Stroke Scale-8 to Detect Large Vessel Occlusion in Ischemic Stroke

Author: Mark W Parsons, Christopher R Levi, Timothy Ang, Ashley R. Garnett, Nicolas R. Smoll, Ferdi Miteff, Allan R. Loudfoot, Neil J. Spratt, Andrew Bivard, Jelle Demeestere, Longting Lin, and Carlos Garcia-Esperon
Subjects: Male, medicine.medical_specialty, Emergency Medical Services, Computed Tomography Angiography, Youden's J statistic, Population, 030204 cardiovascular system & hematology, Brain Ischemia, Decision Support Techniques, 03 medical and health sciences, Disability Evaluation, 0302 clinical medicine, Interquartile range, Predictive Value of Tests, medicine, Humans, cardiovascular diseases, Prospective Studies, education, Stroke, Computed tomography angiography, Aged, Aged, 80 and over, Observer Variation, education.field_of_study, Receiver operating characteristic, medicine.diagnostic_test, business.industry, Rehabilitation, Reproducibility of Results, Middle Aged, medicine.disease, Triage, Checklist, Transportation of Patients, ROC Curve, Predictive value of tests, Area Under Curve, Emergency medicine, Physical therapy, Surgery, Female, Neurology (clinical), Cerebral Arterial Diseases, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery
Abstract: Background Patients with acute ischemic stroke and large vessel occlusion (LVO) may benefit from prehospital identification and transfer to a center offering endovascular therapy. Aims We aimed to assess the accuracy of an existing 8-item stroke scale (National Institutes of Health Stroke Scale-8 [NIHSS-8]) for identification of patients with acute stroke with LVO. Methods We retrospectively calculated NIHSS-8 scores in a population of consecutive patients with presumed acute stroke assessed by emergency medical services (EMS). LVO was identified on admission computed tomography angiography. Accuracy to identify LVO was calculated using receiver operating characteristics analysis. We used weighted Cohen's kappa statistics to assess inter-rater reliability for the NIHSS-8 score between the EMS and the hospital stroke team on a prospectively evaluated subgroup. Results Of the 551 included patients, 381 had a confirmed ischemic stroke and 136 patients had an LVO. NIHSS scores were significantly higher in patients with LVO (median 18; interquartile range 14-22). The NIHSS-8 score reliably predicted the presence of LVO (area under the receiver operating characteristic curve .82). The optimum NIHSS-8 cutoff of 8 or more had a sensitivity of .81, specificity of .75, and Youden index of .56 for prediction of LVO. The EMS and the stroke team reached substantial agreement (κ = .69). Conclusions Accuracy of the NIHSS-8 to identify LVO in a population of patients with suspected acute stroke is comparable to existing prehospital stroke scales. The scale can be performed by EMS with reasonable reliability. Further validation in the field is needed to assess accuracy of the scale to identify patients with LVO eligible for endovascular treatment in a prehospital setting.
Published: 2016

27. Reproducibility of Fluorescent Expression from Engineered Biological Constructs in E. coli

Author: Jacob, Beal, Trac Haddock Angellii, Markus, Gershater, Kim de Mora, Meagan, Lizarazo, Jim, Hollenhorst, Randy, Rettberg, Philipp, Demling, Rene, Hanke, Michae, Osthegel, Anna, Schechtel, Suresh, Sudarsan, Arne, Zimmermann, Bartosz, Gabryelczyk, Martina, Ikonen, Minnamari, Salmela, Muradıye, Acar, Muhammed Fatih Aktas, Furkan, Bestepe, Furkan Sacit Ceylan, Sadık, Cigdem, Mikail, Dohan, Mustafa, Elitok, Mehmet, Gunduz, Esra, Gunduz, Omer Faruk Hatipoglu, Turan, Kaya, Orhan, Sayin, Safa, Tapan, Osman Faruk Tereci, Abdullah, Uçar, Mustafa, Yilmaz, Jeffrey, Barrick, Alex, Gutierrez, Dennis, Mishler, Jordan, Monk, Kate, Mortensen, Nathan, Shin, Ella, Watkins, Yintong, Chen, Yuji, Jin, Yuanjie, Shi, Haoqian Myelin Zhang, Bruno, Ono, Ieda Maria Martinez Paino, Lais, Ribovski, Ivan, Silva, Danilo Keiji Zampronio, Nils, Birkholz, Rudiger Frederik Busche, Oliver, Konzock, Steffen, Lippold, Carsten, Ludwig, Melanie, Philippi, Lukas, Platz, Christian, Sigismund, Susanne, Weber, Maren, Wehrs, Niels, Werchau, Anna, Wronska, Zen Zen Yen, Yash, Agarwal, Evan, Appleton, Douglas, Densmore, Ariela, Esmurria, Kathleen, Lewis, Alan, Pacheco, Marcel, Bruchez, Danielle, Peters, Cheryl, Telmer, Lena, Wang, Silvia Canas Duarte, Daniel Giraldo Perez, Camilo Gomez Garzon, Jorge Madrid Wolff, Nathaly Marin Medina, Valentina, Mazzanti, Laura Rodriguez Forero, Eitan, Scher, Robin, Dowell, Samantha, O’Hara, Cloe Simone Pogoda, Kendra, Shattuck, Ali, Altintas, Anne Pihl Bali, Rasmus, Bech, Anne, Egholm, Anne Sofie Laerke Hansen, Kristian, Jensen, Kristian Barreth Karlsen, Caroline, Mosbech, Sophia, Belkhelfa, Noemie, Berenger, Romain, Bodinier, Cecile, Jacry, Laura Matabishi Bibi, Pierre, Parutto, Julie, Zaworski, Andries de Vries, Freek de Wijs, Rick, Elbert, Lisa, Hielkema, Chandhuru, Jagadeesan, Bayu, Jayawardhana, Oscar, Kuipers, Anna, Lauxen, Thomas, Meijer, Sandra, Mous, Renske van Raaphorst, Aakanksha, Saraf, Otto, Schepers, Oscar, Smits, Jan Willem Veening, Ruud Detert Oude Weme, Lianne, Wieske, Catherine, Ainsworth, Xenia Spencer Milnes, Alejandro, Gómezávila, Eddie Cano Gamez, Ana Laura Torres Huerta, Carlos Alejandro Meza Ramirez, Philipp, Popp, Jara, Radeck, Anna, Sommer, Xiangkai, Li, Qi, Wu, Hongxia, Zhao, Ruixue, Zhao, Irem, Bastuzel, Yasemin, Ceyhan, Mayda, Gursel, Burak, Kizil, Ilkem, Kumru, Yasemin, Kuvvet, Helin, Tercan, Seniz, Yuksel, Luiza, Niyazmetova, Timothy, Ang, Lucas, Black, Ciaran, Kelly, George, Wadhams, Clovis, Basier, Urszula, Czerwinska, Cindy Suci Ananda, Muhammad Al Azhar, Adelia, Elviantari, Maya, Fitriana, Arief Budi Witarto, Yuliant, Jia Fangxing, Qingfeng, Hou, Wan, Pei, Chen, Rifei, Wang, Rong, Huang, Wei, Zhang, Yushan, Jianguo, He, Dengwen, Lai, Pai, Li, Jianheng, Liu, Chunyang, Ni, Qianbin, Zhang, Cinthya, Cadenas, Zardain Canabal, Eduardo J., Claudia Nallely Alonso Cantu, Mercedes Alejandra Vazquez Cantu, Eduardo Cepeda Canedo, Cesar Miguel Valdez Cordova, Jose Alberto de la Paz Espinosa, Carlos Enrique Alavez Garcia, Ana Laura Navarro Heredia, Adriana, Hernandez, Sebastian Valdivieso Jauregui, Eduardo Ramirez Montiel, Eduardo Serna Morales, Yamile Minerva Castellanos Morales, Omar Alonso Cantu Pena, Ramirez Rodríguez, Eduardo A., Elizabeth Vallejo Trejo, Jesus Gilberto Rodriguez Ceja, Jesus Eduardo Martinez Hernandez, Mario Alberto Pena Hernandez, Enrique Amaya Perez, Rebeca Paola Torres Ramirez, Cla, J., Martin, Hanzel, Sarah Mohand Said, Shihab, Sawar, Dylan, Siriwardena, Alex, Tzahristos, Nils, Anlind, Martin, Friberg, Erik, Gullberg, Stephanie, Herman, Dallin, Christensen, Sara, Gertsch, Cody, Maxfield, Charles, Miller, Ryan, Putman, Christine, Bauerl, Estelles Lopez, Lucia T., Estefania Huet Trujillo, Marta Vazquez Vilar, Marlène Sophie Birk, Nico, Claassens, Walter de Koster, Rik van Rosmalen, Wen Ying Wu, Sian, Davies, Dan, Goss, William, Rostain, Chelsey, Tye, Waqar, Yousaf, Natalie, Farny, Chloe, Lajeunesse, Alex, Turland, Chen, An, Jielin, Chen, Yahong, Chen, Zehua, Che, Baishan, Fang, Xiaotong, Fu, Xifeng, Guo, Yue, Jiang, Yiying, Lei, Jianqiao, Li, Zhe, Li, Chang, Liu, Weibing, Liu, Yang, Li, Yizhu, Lv, Qingyu, Ruan, Yue, Su, Chun, Tang, Yushen, Wang, Fan, Wu, Xiaoshan, Yan, Ruihua, Zhang, Tangduo, Zhang, Farren, Isaacs, Ariel Leyva Hernandez, Natalie, Ma, Stephanie, Mao, Yamini, Naidu, Tuukka, Miinalainen, Marion Aruann, Daniel Calendini, Yoann Chabert, Gael Chambonnier, Myriam, Choukour, Ella de Gaulejac, Camille, Houy, Axel, Levier, Loreen, Logger, Sebastien, Nin, Valerie, Prima, Sturgis, James N., Beibei, Fang, Sadik, Cigdem, Abdullah, Ucar, Alejandro, Gutierrez, Revanth, Poondla, Sanjana, Reddy, Tyler, Rocha, Natalie, Schulte, Devin, Wehle, Marta Eva Jackowski, Sean Ross Craig, Ariana Mirzarafie Ahi, Elliott, Parris, Luba, Prout, Barbara, Steijl, Rachel, Wellman, Zhao, Fan, Zhang, Jing, Yang, Wei, Yang, Yuanzhan, Wen, Zhaosen, Evan, Appletion, Jeffrey, Chen, Abha, Patil, Shaheer, Priracha, Kate, Ryan, Nick, Salvador, John, Viola, Boralli, Camila Maria S., Camila Barbosa Bramorski, Juliana Cancino Bernardi, Ana Laura de Lima, Paula Maria Pincela Lins, Cristiane Casonato Melo, Deborah Cezar Mendonca, Thiago, Mosqueiro, Everton, Silva, Graziele, Vasconcelos, Ruchi, Asthana, Donna, Lee, Michelle, Yu, Peter, Choi, Effie, Lau, Kenneth, Lau, Oscar, Ying, Brandon, Malone, Paul, Young, Aidan, Ceney, Dakota, Hawthorne, Sharon, Lian, Sam, Mellentine, Dylan, Miller, Barbara Castro Moreira, Christie, Peebles, Olivia, Smith, Kevin, Walsh, Allison, Zimont, Michael, Brasino, Michael, Donovan, Hannah, Young, Jan, Bejvl, Daniel, Georgiev, Hynek, Kasl, Katerina Pechotova, Vaclav Pelisek, Anna, Sosnova, Pavel, Zach, Anthony, Ciesla, Benjamin, Hoover, Elliott, Chapman, Jon Marles Wright, Vicky, Moynihan, Liusaidh, Owen, Brooke Rothschild Mancinelli, Emilie, Cuillery, Joseph, Heng, Vincent, Jacquot, Paola, Malsot, Rocco, Meli, Cyril, Pulver, Ari, Sarfatis, Loic, Steiner, Victor, Steininger, Nina van Tiel, Gregoire, Thouvenin, Axel, Uran, Lisa, Baumgartner, Anna, Fomitcheva, Daniel, Gerngross, Verena, Jagger, Michael, Meier, Anja, Michel, Jasmine, Bird, Bradley, Brown, Todd, Burlington, Daniel, Herring, Joseph, Slack, Georgina, Westwood, Emilia, Wojcik, Julian, Bender, Julia, Donauer, Ramona, Emig, Rabea, Jesser, Julika, Neumann, Lara, Stuhn, Takema, Hasegawa, Tomoya, Kozakai, Haruka, Maruyama, Sean, Colloms, Charlotte, Flynn, Vilija, Lomeikaite, James, Provan, Kang, Ning, Shuyan, Tang, Guozhao, Wu, Yunjun, Yang, Zhi, Zeng, Zhan, Yi, Pan, Chu, Jun, Li, Keji, Yan, Athale, Chaitanya A., Swapnil, Bodkhe, Manasi, Gangan, Harsh, Gakhare, Yash, Jawale, Snehal, Kadam, Prachiti, Moghe, Gayatri, Mundhe, Neha, Khetan, Ira, Phadke, Prashant, Uniyal, Siddhesh, Zadey, Ines, Cottignie, Eline, Deprez, Astrid, Deryckere, Jasper, Janssens, Frederik, Jonnaert, Katarzyna, Malczewska, Thomas, Pak, Johan, Robben, Ovia Margaret Thirukkumaran, Vincent Van Deuren, Laurens, Vandebroek, Laura Van Hese, Laetitia Van Wonterghem, Leen, Verschooten, Moritz, Wolter, Joss, Auty, Richard, Badge, Liam, Crawford, Raymond, Dalgleish, Amy, Evans, Cameron, Grundy, Charlie, Kruczko, Payal, Karia, Graeme, Glaister, Rhys, Hakstol, Seme, Mate, Karin, Otero, Dustin, Smith, Jeff, Tingley, Hans Joachim Wieden, Haotian, Wang, Ningning, Yao, Matthias, Franz, Anna, Knoerlein, Nicolas, Koutsoubelis, Loechner, Anne C., Max, Mundt, Alexandra, Richter, Oliver, Schauer, Marjorie, Buss, Sivateja, Tangirala, Brian, Teague, Tianyi, Huang, Xinhao, Song, Yibing, Wei, Zhaoran, Zhang, Longzhi, Cao, Cheng Li, Kang Yang, Zhiqin, Chen, Yuxing, Fang, Libo, Sun, Weiyi, Wang, Yang, Yang, David, Adams, Joshua, Colls, Joshua, Timmons, David, Urick, Julia Anna Adrian, Madina, Akan, Youssef, Chahibi, Rahmi, Lale, Typhaine Le Doujet, Marit Vaagen Roee, Altynay, Abdirakhmanova, Askarbek, Orakov, Azhar, Zhailauova, Jinyang, Liang, Yu, Ma, Qikai, Qin, Yetian, Su, Ju Yeon Han, Raphaella, Hull, Wei Chung Kong, Li Chieh Lu, Duke, Quinton, Pauline, Aubert, Johan, Bourdarias, Olivier, Bugaud, Coralie Demon Chaine, Isabelle, Hatin, Ibtissam Kaid Slimane, Seong Koo Kang, Audrey, Moatti, Cheikh Fall Ndiaye, Mathilde, Ananos, Alexander, Arkhipenko, Valentin, Bailly, Jules, Caput, Javier, Castillo, Alma Chapet Batlle, Floriane, Cherrier, Claudia Demarta Gatsi, Deshmukh, Gopaul, Muriel, Gugger, Caroline, Lambert, Lucas, Krauss, Amelie, Vandendaele, Xiaojing, Li, Lin, Xiaomei, Luo Xunxun, Anders C. h. r. Hansen, Tina, Kronborg, Pettersen, Jens S., Charles, Calvet, Tyler Dae Devlin, Kosuke, Fujishima, Danny, Greenberg, Tina, Ju, Ryan, Kent, Daniel, Kunin, Erica, Lieberman, Griffin, Mccutcheon, Thai, Nguyen, Lynn, Rothschild, Shih, Joseph D., Jack, Takahashi, Kirsten, Thompson, Forrest, Tran, Daniel, Xiang, Felix, Richter, Yang, Xiaoran, Xiangyue, Hu, Changyuan, Deng, Shuyu, Hua, Yumeng, Li, Xinyu, Meng, Boxiang, Wang, Yingqi, Wang, Xuan, Wang, Zixuan, Xu, Jieyu, Yan, Ming, Yan, Yineng, Zhou, Edgar Alberto Alcalá Orozco, José Alberto Cristerna Bermúdez, Daniela Flores Gómez, José Ernesto Hernández Castañeda, Diana Clarisse Montaño Navarro, Juana Yessica PérezÁvila, María Fernanda Salazar Figueroa, María Fernanda Sánchez Arroyo, Oliva Angélica Sánchez Montesinos, Ángel Farid Rojas Cruz, Carlos Ramos Gutiérrez, Alonso Pérez Lona, Carlos Alejandro Meza Ramírez, Fernanda Sotomayor Olivares, Jorge Sebastián Rodríguez Iniesta, Juan Carlos Rueda Silva, Shotaro, Ayukawa, Takahiro, Kashiwagi, Daisuke, Kiga, Misa, Minegishi, Riku, Shinohara, Hiraku, Tokuma, Yuta, Yamazaki, Shuhei, Yasunishi, Erinn Sim Zixuan, Remsha, Afzal, Matthew, Carrigan, Barry, Moran, Marlena, Mucha, Arnas, Petrauskas, Stefan, Marsden, Michelle, Post, Anne, Rodenburg, Hector, Sanguesa, Marit van der Does, Erwin van Rijn, Max van’t Hof, Yeshi de Bruin, Hans de Ferrante, Elles, Elschot, Laura, Jacobs, Jan Willem Muller, Sjoerd, Nooijens, Femke, Vaassen, Cas van der Putten, Esther van Leeuwen, Laura van Smeden, Kwan Kwan Zhu, Kevin, Sabath, Katharina, Sporbeck, Nicolai von Kügelgen, Lisa, Wellinger, Stefanie, Braun, Jack, Ho, Yash, Mishra, Mariola, Sebastian, Lucas von Chamier, Ahsan, Fasih M., Satyadi, Megan A., Vivienne, Gunadhi, Phillip, Kyriakakis, Jenny, Lee, Walter, Thavarajah, Kimia, Abtahi, Robert, Hand, Chun Mun Loke, Adam, Wahab, Iowis, Zhu, Del Bianco, Cristina, Chizzolini, Fabio, Elisa, Godino, Lentini, Roberta, Mansy, Sheref Samir, Yeh Martin, Noel, Claudio Oss Pegorar, Alexander, Cook, Timothy, Kerns, Chad, Nielsen, Michael, Paskett, Alexander, Torgesen, Stephen, Lee, Ophir, Ospovat, Sikandar, Raza, Daniel, Shaykevich, Jarrod, Shilts, Barbora, Bajorinaite, Mykolas, Bendorius, Ieva, Rauluseviciute, Ieva, Savickyte, Sarunas, Tumas, William, Buchser, Elli, Cryan, Caroline, Golino, Andrew, Halleran, Taylor, Jacobs, Michael, Lefew, Joe, Maniaci, John, Marken, Margaret, Saha, Panya, Vij, Kayla, Desanty, Julie, Mazza, Raytheon BBN Technologies, iGEM Foundation, Synthace, Agilent Technology [Santa Clara], Raytheon BBN Technologies, Synthace, and Agilent provided support in the form of salaries for authors JB, MG, and JH, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the author contributions section, The authors wish to thank Sarah Munro and Marc Salit of NIST for help in designing this study. Consortium authors include all persons self-identified by contributing teams as deserving co-authorship credit. Contributors are listed alphabetically within team, and teams alphabetically and by year. Note that some persons may be credited as contributing in both years. Team names are given as identified in iGEM records: full details of each team’s institution and additional members may be found online in the iGEM Foundation archives at:http://year.igem.org/Team:name e.g.: full information on the 2015 ETH_Zurich team may be found at: http://2015.igem.org/Team:ETH_Zurich, BBN Technologies, IGEM Foundation, Synthace Ltd., Agilent Technologies, Department of Biotechnology and Chemical Technology, Helsinki Institute for Information Technology HIIT, ATOMS Turkiye, Boston University, Carnegie Mellon University, Technical University of Denmark, Ludwig Maximilian University of Munich, Middle East Technical University, Sumbawa University of Technology, Southern University of Science and Technology, Sun Yat-Sen University, Tecnológico de Monterrey, Universidad Autonoma de Nuevo Leon, University of Ottawa, Universitat Politècnica de València, Wageningen University and Research Centre, Worcester Polytechnic Institute, Xiamen University, University of Texas at Austin, Bielefeld University, Birkbeck University of London, USP-Brazil, City University of Hong Kong, Colorado State University, CU Boulder, Swiss Federal Institute of Technology Lausanne, Swiss Federal Institute of Technology Zurich, University of Exeter, Indian Institute of Science Education and Research, KU Leuven, Massachusetts Institute of Technology, Northeast Agricultural University, Nanjing Agricultural University, Norwegian University of Science and Technology, Ocean University of China, University of Southern Denmark, Shenzhen Middle School - SZMS 15, Tokyo Institute of Technology, Trinity College Dublin, Delft University of Technology, Eindhoven University of Technology, Tuebingen, University of California Los Angeles, University of California San Diego, University of Maryland, University of Trento, Vanderbilt University, College of William and Mary, Department of Bioproducts and Biosystems, Aalto-yliopisto, Aalto University, Jones, D Dafydd, Discrete Technology and Production Automation, and Robotics and image-guided minimally-invasive surgery (ROBOTICS)
Subjects: 0106 biological sciences, 0301 basic medicine, green fluorescent protein, Laboratory Proficiency Testing, Transcription, Genetic, International Genetically Engineered Machine, [SDV]Life Sciences [q-bio], lcsh:Medicine, Protein Engineering, 01 natural sciences, Infographics, Synthetic biology, genetics, lcsh:Science, Promoter Regions, Genetic, Macromolecular Engineering, transcription initiation, Measurement, Multidisciplinary, Chemistry, Strain (biology), gene expression regulation, good laboratory practice, Research Assessment, Fluorescence, Reproducibility, 3. Good health, Bioassays and Physiological Analysis, Engineering and Technology, Educational Status, Synthetic Biology, Genetic Engineering, Transcription, Graphs, Research Article, Biotechnology, Transcriptional Activation, Computer and Information Sciences, General Science & Technology, Green Fluorescent Proteins, Bioengineering, Computational biology, iGEM Interlab Study Contributors, Research and Analysis Methods, Promoter Regions, 03 medical and health sciences, promoter region, Genetic, 010608 biotechnology, Escherichia coli, ta215, business.industry, Data Visualization, lcsh:R, Fluorescence Competition, genetic transcription, DNA structure, Reproducibility of Results, Biology and Life Sciences, protein engineering, 030104 developmental biology, Good Health and Well Being, 7 INGENIERÍA Y TECNOLOGÍA, Synthetic Bioengineering, People and Places, lcsh:Q, Population Groupings, biosynthesis, business, metabolism, Undergraduates
Abstract: We present results of the first large-scale interlaboratory study carried out in synthetic biology, as part of the 2014 and 2015 International Genetically Engineered Machine (iGEM) competitions. Participants at 88 institutions around the world measured fluorescence from three engineered constitutive constructs in E. coli. Few participants were able to measure absolute fluorescence, so data was analyzed in terms of ratios. Precision was strongly related to fluorescent strength, ranging from 1.54-fold standard deviation for the ratio between strong promoters to 5.75-fold for the ratio between the strongest and weakest promoter, and while host strain did not affect expression ratios, choice of instrument did. This result shows that high quantitative precision and reproducibility of results is possible, while at the same time indicating areas needing improved laboratory practices. Copyright: © 2016 Beal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Published: 2016

28. Exploring the eukaryotic Yip and REEP/Yop superfamily of membrane-shaping adapter proteins (MSAPs): A cacophony or harmony of structure and function?

Author: Timothy Angelotti
Subjects: endoplasmic reticulum, golgi, hereditary spastic paraplegia, membrane-shaping adapter protein, YIPF, Yif, Biology (General), QH301-705.5
Abstract: Polytopic cargo proteins are synthesized and exported along the secretory pathway from the endoplasmic reticulum (ER), through the Golgi apparatus, with eventual insertion into the plasma membrane (PM). While searching for proteins that could enhance cell surface expression of olfactory receptors, a new family of proteins termed “receptor expression-enhancing proteins” or REEPs were identified. These membrane-shaping hairpin proteins serve as adapters, interacting with intracellular transport machinery, to regulate cargo protein trafficking. However, REEPs belong to a larger family of proteins, the Yip (Ypt-interacting protein) family, conserved in yeast and higher eukaryotes. To date, eighteen mammalian Yip family members, divided into four subfamilies (Yipf, REEP, Yif, and PRAF), have been identified. Yeast research has revealed many intriguing aspects of yeast Yip function, functions that have not completely been explored with mammalian Yip family members. This review and analysis will clarify the different Yip family nomenclature that have encumbered prior comparisons between yeast, plants, and eukaryotic family members, to provide a more complete understanding of their interacting proteins, membrane topology, organelle localization, and role as regulators of cargo trafficking and localization. In addition, the biological role of membrane shaping and sensing hairpin and amphipathic helical domains of various Yip proteins and their potential cellular functions will be described. Lastly, this review will discuss the concept of Yip proteins as members of a larger superfamily of membrane-shaping adapter proteins (MSAPs), proteins that both shape membranes via membrane-sensing and hairpin insertion, and well as act as adapters for protein-protein interactions. MSAPs are defined by their localization to specific membranes, ability to alter membrane structure, interactions with other proteins via specific domains, and specific interactions/effects on cargo proteins.
Published: 2022
Full Text: View/download PDF

29. The Utility of Color Doppler to Confirm Endotracheal Tube Placement: A Pilot Study

Author: Thomas H. Gildea, Kenton L. Anderson, Kian R. Niknam, Laleh Gharahbaghian, Sarah R. Williams, Timothy Angelotti, Paul S. Auerbach, and Viveta Lobo
Subjects: Medicine, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Introduction: Grayscale ultrasound (US) imaging has been used as an adjunct for confirming endotracheal tube (ETT) placement in recent years. The addition of color Doppler imaging (CDI) has been proposed to improve identification but has not been well studied. The aim of this study was to assess whether CDI improves correct localization of ETT placement. Methods: A convenience sample of emergency and critical care physicians at various levels of training and experience participated in an online assessment. Participants viewed US video clips of patients, which included either tracheal or esophageal intubations captured in grayscale or with CDI; there were five videos of each for a total of 20 videos. Participants were asked to watch each clip and then assess the location of the ETT. Results: Thirty-eight subjects participated in the online assessment. Levels of training included medical students (13%), emergency medicine (EM) residents (50%), EM attendings (32%), and critical care attendings (5%). The odds ratio of properly assessing tracheal placement using color relative to a grayscale imaging technique was 1.5 (p = 0.21). Regarding the correct assessment of esophageal placement, CDI had 1.4 times the odds of being correctly assessed relative to grayscale (p = 0.26). The relationship between training level and correct assessments was not significant for either tracheal or esophageal placements. Conclusion: In this pilot study we found no significant improvement in correct identification of ETT placement using color Doppler compared to grayscale ultrasound; however, there was a trend toward improvement that might be better elucidated in a larger study.
Published: 2020
Full Text: View/download PDF

30. Correction: REEPs Are Membrane Shaping Adapter Proteins That Modulate Specific G Protein-Coupled Receptor Trafficking by Affecting ER Cargo Capacity.

Author: Susann Björk, Carl M. Hurt, Vincent K. Ho, and Timothy Angelotti
Subjects: Medicine, Science
Published: 2013
Full Text: View/download PDF

31. REEPs are membrane shaping adapter proteins that modulate specific g protein-coupled receptor trafficking by affecting ER cargo capacity.

Author: Susann Björk, Carl M Hurt, Vincent K Ho, and Timothy Angelotti
Subjects: Medicine, Science
Abstract: Receptor expression enhancing proteins (REEPs) were identified by their ability to enhance cell surface expression of a subset of G protein-coupled receptors (GPCRs), specifically GPCRs that have proven difficult to express in heterologous cell systems. Further analysis revealed that they belong to the Yip (Ypt-interacting protein) family and that some REEP subtypes affect ER structure. Yip family comparisons have established other potential roles for REEPs, including regulation of ER-Golgi transport and processing/neuronal localization of cargo proteins. However, these other potential REEP functions and the mechanism by which they selectively enhance GPCR cell surface expression have not been clarified. By utilizing several REEP family members (REEP1, REEP2, and REEP6) and model GPCRs (α2A and α2C adrenergic receptors), we examined REEP regulation of GPCR plasma membrane expression, intracellular processing, and trafficking. Using a combination of immunolocalization and biochemical methods, we demonstrated that this REEP subset is localized primarily to ER, but not plasma membranes. Single cell analysis demonstrated that these REEPs do not specifically enhance surface expression of all GPCRs, but affect ER cargo capacity of specific GPCRs and thus their surface expression. REEP co-expression with α2 adrenergic receptors (ARs) revealed that this REEP subset interacts with and alter glycosidic processing of α2C, but not α2A ARs, demonstrating selective interaction with cargo proteins. Specifically, these REEPs enhanced expression of and interacted with minimally/non-glycosylated forms of α2C ARs. Most importantly, expression of a mutant REEP1 allele (hereditary spastic paraplegia SPG31) lacking the carboxyl terminus led to loss of this interaction. Thus specific REEP isoforms have additional intracellular functions besides altering ER structure, such as enhancing ER cargo capacity, regulating ER-Golgi processing, and interacting with select cargo proteins. Therefore, some REEPs can be further described as ER membrane shaping adapter proteins.
Published: 2013
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources

Refine your results

31 results on '"Timothy Ang"'

1. Relationship Between Baseline Infarct and Clinical Outcome in Pediatric Large‐Vessel Occlusion Ischemic Stroke

2. Rollout of a statewide Australian telestroke network including virtual reality training is associated with improved hyperacute stroke workflow metrics and thrombolysis rate

3. Movable typing of full‐lumen personalized Vein‐Chips to model cerebral venous sinus thrombosis

4. Microvasculature‐on‐a‐Post Chip That Recapitulates Prothrombotic Vascular Geometries and 3D Flow Disturbance

5. Telestroke Assessment With Perfusion CT Improves the Diagnostic Accuracy of Stroke vs. Mimic

6. Endovascular Thrombectomy for Ischemic Stroke Increases Disability-Free Survival, Quality of Life, and Life Expectancy and Reduces Cost

7. Tenecteplase Treatment and Thrombus Characteristics Associated With Early Reperfusion: An EXTEND-IA TNK Trials Analysis

8. Ultra-Long Transfers for Endovascular Thrombectomy—Mission Impossible?: The Australia-New Zealand Experience

9. Novel Movable Typing for Personalized Vein‐Chips in Large Scale: Recapitulate Patient‐Specific Virchow's Triad and its Contribution to Cerebral Venous Sinus Thrombosis

10. Optic nerve sheath fenestration for treating papilloedema in the era of cerebral venous sinus stenting

11. Thrombectomy Improves Outcomes in Paediatric Large Vessel Occlusion Stroke: A Case-Control Study

12. Transverse Sinus Stenting Reverses Medically Refractory Idiopathic Intracranial Hypertension

13. Diagnostic Utility of Computed Tomography Perfusion in the Telestroke Setting

14. Incidence and Natural History of Pediatric Large Vessel Occlusion Stroke: A Population Study

15. 029 High Sensitivity Troponin in Acute Ischaemic Stroke Study (TACIS)

16. Current perspectives on neuroimaging techniques used to identify stroke mimics in clinical practice

17. Tenecteplase versus alteplase before endovascular thrombectomy (EXTEND-IA TNK): A multicenter, randomized, controlled study

18. The establishment of a telestroke service using multimodal CT imaging decision assistance: 'Turning on the fog lights'

19. Mechanical thrombectomy in pediatric stroke: systematic review, individual patient data meta-analysis, and case series

20. Extending thrombolysis to 4·5–9 h and wake-up stroke using perfusion imaging. a systematic review and meta-analysis of individual patient data

21. Penumbral imaging and functional outcome in patients with anterior circulation ischaemic stroke treated with endovascular thrombectomy versus medical therapy: a meta-analysis of individual patient-level data

22. Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke

23. Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data

24. Multi-Modal CT in Acute Stroke: Wait for a Serum Creatinine before Giving Intravenous Contrast? No!

25. Endovascular Therapy for Ischemic Stroke with Perfusion-Imaging Selection

26. Validation of the National Institutes of Health Stroke Scale-8 to Detect Large Vessel Occlusion in Ischemic Stroke

27. Reproducibility of Fluorescent Expression from Engineered Biological Constructs in E. coli

28. Exploring the eukaryotic Yip and REEP/Yop superfamily of membrane-shaping adapter proteins (MSAPs): A cacophony or harmony of structure and function?

29. The Utility of Color Doppler to Confirm Endotracheal Tube Placement: A Pilot Study

30. Correction: REEPs Are Membrane Shaping Adapter Proteins That Modulate Specific G Protein-Coupled Receptor Trafficking by Affecting ER Cargo Capacity.

31. REEPs are membrane shaping adapter proteins that modulate specific g protein-coupled receptor trafficking by affecting ER cargo capacity.

Catalog

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

31 results on '"Timothy Ang"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources