Podcasts about acute ischemic stroke

Two new trials published in JAMA evaluate the efficacy of periprocedural intra-arterial thrombolytics after successful endovascular thrombectomy for patients with acute ischemic stroke. Diederik Dippel, MD, PhD, of Erasmus University Medical Center discusses this and more with JAMA Deputy Editor Christopher C. Muth, MD. Related Content: Intra-Arterial Thrombolytics During Thrombectomy for Ischemic Stroke—End of the Story or a New Beginning? Intra-Arterial Tenecteplase Following Endovascular Reperfusion for Large Vessel Occlusion Acute Ischemic Stroke Intra-Arterial Urokinase After Endovascular Reperfusion for Acute Ischemic Stroke

Darshan H. Brahmbhatt, Podcast Editor of JACC: Advances, discusses a recently published original research paper on social vulnerability index and all-cause mortality after acute ischemic stroke for a Medicare Cohort from 2020-2023.

Dr. Linda Chu discusses the assessment of thrombectomy vs. combined thrombolysis and thrombectomy in patients with acute ischemic stroke and medium vessel occlusion with Dr. Adam Dmytriw and Dr. Adrien Guenego.   Assessment of Thrombectomy versus Combined Thrombolysis and Thrombectomy in Patients with Acute Ischemic Stroke and Medium Vessel Occlusion. The MAD-MT Consortium. Radiology 2024; 312(2):e233041. 

Can a new drug slow the progression of Alzheimer's disease? Find out about this and more in today's PeerDirect Medical News Podcast.

Show notes at pharmacyjoe.com/episode933. In this episode, I'll discuss tenecteplase for stroke from 4.5 to 24 hours after the time last know well. The post 933: Can tenecteplase be used for acute ischemic stroke beyond 4.5 hours from time last know well? appeared first on Pharmacy Joe.

Joanne e João Urbano, nosso Joca, convidam o Dr. Igor Brum para conversar sobre as últimas atualizações no manejo de AVC isquêmico. Referências: 1. Hilkens NA, Casolla B, Leung TW, de Leeuw FE. Stroke. Lancet. Published online May 14, 2024. doi:10.1016/S0140-6736(24)00642-1 2. Huo X, Ma G, Tong X, et al. Trial of Endovascular Therapy for Acute Ischemic Stroke with Large Infarct. N Engl J Med. 2023;388(14):1272-1283. doi:10.1056/NEJMoa2213379 3. Sarraj A, Hassan AE, Abraham MG, et al. Trial of Endovascular Thrombectomy for Large Ischemic Strokes [published correction appears in N Engl J Med. 2024 Jan 25;390(4):388. doi: 10.1056/NEJMx230009]. N Engl J Med. 2023;388(14):1259-1271. doi:10.1056/NEJMoa2214403 4. Strbian D, Tsivgoulis G, Ospel JM, et al. European Stroke Organisation (ESO) and European Society for Minimally Invasive Neurological Therapy (ESMINT) Guideline on Acute Management of Basilar Artery Occlusion. Eur Stroke J. Published online May 16, 2024. doi:10.1177/23969873241257223

Contributor: Travis Barlock MD Educational Pearls: Thrombolytic therapy (tPA or TNK) is often used in the ED for strokes Use of anticoagulants with INR > 1.7 or  PT >15 Warfarin will reliably increase the INR Current use of Direct thrombin inhibitor or Factor Xa inhibitor  aPTT/PT/INR are insufficient to assess the degree of anticoagulant effect of Factor Xa inhibitors like apixaban (Eliquis) and rivaroxaban (Xarelto)  Intracranial or intraspinal surgery in the last 3 months Intracranial neoplasms or arteriovenous malformations also increase the risk of bleeding Current intracranial or subarachnoid hemorrhage History of intracranial hemorrhage from thrombolytic therapy also contraindicates tPA/TNK Recent (within 21 days) or active gastrointestinal bleed Hypertension BP >185 systolic or >110 diastolic Administer labetalol before thrombolytics to lower blood pressure Timing of symptoms Onset > 4.5 hours contraindicates tPA Platelet count < 100,000 BGL < 50 Potential alternative explanation for stroke-like symptoms obviating need for thrombolytics References 1. Fugate JE, Rabinstein AA. Absolute and Relative Contraindications to IV rt-PA for Acute Ischemic Stroke. The Neurohospitalist. 2015;5(3):110-121. doi:10.1177/1941874415578532 2. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the Early Management of Patients with Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke a Guideline for Healthcare Professionals from the American Heart Association/American Stroke Association. Vol 50.; 2019. doi:10.1161/STR.0000000000000211 Summarized by Jorge Chalit, OMSII | Edited by Jorge Chalit

Reference: Albers GW et al. TIMELESS Investigators. Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection. NEJM Feb 2024 Date: April 12, 2024 Guest Skeptic: Dr. Vasisht Srinivasan is an Emergency Medicine physician and neurointensivist at the University of Washington and Harborview Medical Center in Seattle, WA. He is an assistant professor in Emergency […] The post SGEM#436: For the Longest Time – To Give TNK for an Acute Ischemic Stroke first appeared on The Skeptics Guide to Emergency Medicine.

CME credits: 1.50 Valid until: 27-02-2025 Claim your CME credit at https://reachmd.com/programs/cme/emerging-data-in-the-management-of-acute-ischemic-stroketia/18133/ This program addresses critical gaps in healthcare professionals' knowledge and practice related to the secondary prevention of a clot-related stroke in patients with an acute ischemic stroke or at high risk for TIA. By addressing these gaps and achieving the outlined learning objectives, participants will be better equipped to provide optimal patient care, ultimately improving outcomes in managing this critical medical condition.

In this episode of the BackTable Podcast, guest host Dr. Krishna Amuluru interviews Dr. Fawaz Al-Mufti about recent trials on large core strokes and how they may impact practice. Dr. Al-Mufti is a practicing neurointerventionalist and serves as the Associate Chair of Neurology for Research at New York Medical College. Dr. Al-Mufti examines the cost-effectiveness and socioeconomic implications of successful treatment of patients with large core strokes. The doctors highlight various stroke thrombectomy trials including the RESCUE-Japan, SELECT2 Trial, and TENSION trials. The discussion also covers how these findings affect thrombectomy expansion in lower resource settings and the future outlook of endovascular thrombectomy procedures. --- CHECK OUT OUR SPONSOR RADPAD® Radiation Protection https://www.radpad.com/ --- SHOW NOTES 00:00 - Introduction 02:53 - Large Ischemic Core Infarcts 06:06 - The Importance of ASPECTS 11:59 - Large Ischemic Core Trials 23:37 - Socioeconomic Implications of Thrombectomy 38:08 - The Future of Thrombectomy --- RESOURCES Mission Thrombectomy: https://missionthrombectomy.org/ The Alberta Stroke Program Early CT score (ASPECTS): A predictor of mortality in acute ischemic stroke: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515558/ Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomized trials (HERMES Study): https://doi.org/10.1016/S0140-6736(16)00163-X Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging (DEFUSE III Trial): https://www.nejm.org/doi/full/10.1056/nejmoa1713973 Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct (DAWN Trial): https://www.nejm.org/doi/full/10.1056/nejmoa1706442 Endovascular Therapy for Acute Stroke with a Large Ischemic Region (RESCUE-Japan Trial): https://www.nejm.org/doi/full/10.1056/nejmoa2118191 Trial of Endovascular Thrombectomy for Large Ischemic Strokes (SELECT2 Trial): https://www.nejm.org/doi/full/10.1056/NEJMoa2214403 TESLA Trial: Rationale, Protocol, and Design: https://www.ahajournals.org/doi/10.1161/SVIN.122.000787 Endovascular thrombectomy for acute ischaemic stroke with established large infarct: multicentre, open-label, randomized trial (TENSION Trial): https://www.sciencedirect.com/science/article/pii/S0140673623020329 Evaluation of acute mechanical revascularization in large stroke (ASPECTS ⩽5) and large vessel occlusion within 7 h of last-seen-well: The LASTE multicenter, randomized, clinical trial protocol: https://pubmed.ncbi.nlm.nih.gov/37462028/ Trial of Endovascular Therapy for Acute Ischemic Stroke with Large Infarct (ANGEL-ASPECT Trial): https://www.nejm.org/doi/full/10.1056/NEJMoa2213379 Acute endovascular stroke therapy (Dr. Mike Chen Review): https://pubmed.ncbi.nlm.nih.gov/20535000/ Mechanical thrombectomy is cost-effective versus medical management alone around Europe in patients with low ASPECTS (European Cost Effectiveness Study): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313965/ Mechanical Thrombectomy Global Access For Stroke (MT-GLASS): A Mission Thrombectomy (MT-2020 Plus) Study: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313965/ Noncontrast Computed Tomography vs Computed Tomography Perfusion or Magnetic Resonance Imaging Selection in Late Presentation of Stroke With Large-Vessel Occlusion: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576630/

In this episode, we review the role and indications of thrombolytics in acute ischemic stroke. The efficacy, safety, administration considerations, and cost between alteplase and tenecteplase are compared and contrasted. Key Concepts Alteplase (Activase) is a recombinant DNA version of human TPA (tissue plasminogen activator). Tenecteplase (TNKase) is similar to human TPA except it has three amino acid changes that result in a longer half-life and higher fibrin specificity. In patients with stroke, alteplase is given as a bolus followed by a 60-minute infusion. Tenecteplase is given as an IV bolus without the need for an infusion due to its longer half-life. Tenecteplase is at least as safe and effective as alteplase in acute ischemic stroke (with some studies showing greater benefit with tenecteplase). In patients with acute ischemic stroke who are candidates for mechanical thrombectomy, thrombolytics (with alteplase or tenecteplase) will still be given in patients who meet inclusion criteria and have no exclusion criteria. References Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association [published correction appears in Stroke. 2019 Dec;50(12):e440-e441]. Stroke. 2019;50(12):e344-e418. doi:10.1161/STR.0000000000000211 Campbell BCV, Mitchell PJ, Churilov L, et al. Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke. N Engl J Med. 2018;378(17):1573-1582. doi:10.1056/NEJMoa1716405 Kobeissi H, Ghozy S, Turfe B, et al. Tenecteplase vs. alteplase for treatment of acute ischemic stroke: A systematic review and meta-analysis of randomized trials. Front Neurol. 2023;14:1102463. Published 2023 Jan 23. doi:10.3389/fneur.2023.1102463

JNIS Editor-in-Chief, Dr. Felipe C. Albuquerque, is joined from Calgary by Dr. Johanna Ospel (1) to discuss "Recent developments in pre-hospital and in-hospital triage for endovascular stroke treatment", a paper detailing the many aspects of resource allocation when treating stroke patients.  Read the paper: https://jnis.bmj.com/content/early/2022/10/14/jnis-2021-018547 (1) Departments of Radiology and Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada Please subscribe to the JNIS Podcast via all podcast platforms, including Apple Podcasts, Google Podcasts, Stitcher and Spotify, to get the latest episodes. Also, please consider leaving us a review or a comment on the JNIS Podcast iTunes page: https://podcasts.apple.com/gb/podcast/jnis-podcast/id942473767  Thank you for listening! This episode was produced and edited by Brian O'Toole. 

Listen to the fourth episode of NCS's INSIGHTS series on Acute Ischemic Stroke (part 2 of 2) The INSIGHTS series is hosted by Casey Albin, MD and Salia Farrokh, PharmD, and covers different topics from Neurocritical Care ON CALL®, the only up-to-date, comprehensive resource to offer content exclusively dedicated to the practice of neurocritical care. Learn more about ON CALL®. This episode is sponsored by Biogen. Science that transforms patient lives. Science that seeks to solve societal problems. Science that acts with purpose. Science that is inspired by the diversity and passion of our people. Discover where science meets humanity at Biogen. The NCS Podcast is the official podcast of the Neurocritical Care Society.

Listen to the third episode of NCS' INSIGHTS series - Acute Ischemic Stroke (part 1 of 2). The INSIGHTS series is hosted by Casey Albin, MD and Salia Farrokh, PharmD, and covers different topics from Neurocritical Care ON CALL®, the only up-to-date, comprehensive resource to offer content exclusively dedicated to the practice of neurocritical care. Learn more about ON CALL®. This episode is sponsored by Biogen. Science that transforms patient lives. Science that seeks to solve societal problems. Science that acts with purpose. Science that is inspired by the diversity and passion of our people. Discover where science meets humanity at Biogen. The NCS Podcast is the official podcast of the Neurocritical Care Society.

Dr. Thanh Nguyen discusses his paper, "Dual Antiplatelet Therapy vs Alteplase for Patients With Minor Nondisabling Acute Ischemic Stroke". Show references: https://jamanetwork.com/journals/jama/article-abstract/2806532 This episode was sponsored by the ExTINGUISH Trial for NMDAR Encephalitis: Call 844-4BRAIN5 to refer patients.

Dr. Dan Ackerman talks with Dr. Thanh Nguyen about whether dual antiplatelet therapy is noninferior to intravenous thrombolysis among patients with minor nondisabling acute ischemic stroke. Read the related article in JAMA. Visit NPUb.org/Podcast for associated article links. This episode was sponsored by the ExTINGUISH Trial for NMDAR Encephalitis: Call 844-4BRAIN5 to refer patients.

"...the World Health Organization definition of stroke is rapidly developing clinical signs of focal or Global disturbance of cerebral function with symptoms lasting 24 hours or longer or leading to death with no apparent cause other than a vascular origin this means that patients with similar symptoms caused by other causes such as tumors subdural hematomas poisoning or trauma and not considered Strokes so the difference between a stroke and a TI a or a transient ischemic attack is that a TI a is a brief episode of neurological dysfunction typically less than one hour but up to 24 hours with a vascular cause and with no evidence of infarction meaning cell death on Imaging they were previously distinguished by the duration of the neurological symptoms but now a distinguished based on the absence of in fact evidence on it Jing and resolution of symptoms the two main types of stroke ischemic stroke or hemorrhagic stroke with around 80% being ischemic an ischemic stroke is caused by the blockage of blood flow while a hemorrhagic stroke is caused by a rupture and extravasation of blood in the brain or surrounding tissue also note that Strokes with ischemic areas have a risk for breeding there for ischemic stroke can undergo what is known as a hammer dragic transformation there are four main mechanisms for an ischemic stroke the first is thrombosis which is divided into large and small vessel disease large vessel disease involves the common and internal carotid 's the vertebral arteries and The Circle of Willis the main causes of thrombi here include atherosclerosis vasoconstriction dissection and vasculitis small vessel disease involves smaller she's of The Circle of Willis and arteries in the distal vertebral and battler arteries causes here include lightbulb highly gnosis which is a build-up of fatty hyelin matter secondary to hypertension and aging as well as micro after ohms which is small atherosclerosis plaques thrombi can also be caused by Sickle Cell red blood cells clumping together and thrombi may also generate emboli which are the second mechanism for ischemic stroke the emboli are entities that travel in the blood and can be part of a thrombus that has been broken off they can be fat they can be air or even cancer or clumps of bacteria most commonly the source of the embolus is the heart due to atrial fibrillation atrial or ventricular thrombi rheumatic heart disease recent myocardial infarction or even recent coronary artery bypass grafting emboli may also travel from sources..." Learn more about your ad choices. Visit megaphone.fm/adchoices

"...the World Health Organization definition of stroke is rapidly developing clinical signs of focal or Global disturbance of cerebral function with symptoms lasting 24 hours or longer or leading to death with no apparent cause other than a vascular origin this means that patients with similar symptoms caused by other causes such as tumors subdural hematomas poisoning or trauma and not considered Strokes so the difference between a stroke and a TI a or a transient ischemic attack is that a TI a is a brief episode of neurological dysfunction typically less than one hour but up to 24 hours with a vascular cause and with no evidence of infarction meaning cell death on Imaging they were previously distinguished by the duration of the neurological symptoms but now a distinguished based on the absence of in fact evidence on it Jing and resolution of symptoms the two main types of stroke ischemic stroke or hemorrhagic stroke with around 80% being ischemic an ischemic stroke is caused by the blockage of blood flow while a hemorrhagic stroke is caused by a rupture and extravasation of blood in the brain or surrounding tissue also note that Strokes with ischemic areas have a risk for breeding there for ischemic stroke can undergo what is known as a hammer dragic transformation there are four main mechanisms for an ischemic stroke the first is thrombosis which is divided into large and small vessel disease large vessel disease involves the common and internal carotid 's the vertebral arteries and The Circle of Willis the main causes of thrombi here include atherosclerosis vasoconstriction dissection and vasculitis small vessel disease involves smaller she's of The Circle of Willis and arteries in the distal vertebral and battler arteries causes here include lightbulb highly gnosis which is a build-up of fatty hyelin matter secondary to hypertension and aging as well as micro after ohms which is small atherosclerosis plaques thrombi can also be caused by Sickle Cell red blood cells clumping together and thrombi may also generate emboli which are the second mechanism for ischemic stroke the emboli are entities that travel in the blood and can be part of a thrombus that has been broken off they can be fat they can be air or even cancer or clumps of bacteria most commonly the source of the embolus is the heart due to atrial fibrillation atrial or ventricular thrombi rheumatic heart disease recent myocardial infarction or even recent coronary artery bypass grafting emboli may also travel from sources..." Learn more about your ad choices. Visit megaphone.fm/adchoices

"...the World Health Organization definition of stroke is rapidly developing clinical signs of focal or Global disturbance of cerebral function with symptoms lasting 24 hours or longer or leading to death with no apparent cause other than a vascular origin this means that patients with similar symptoms caused by other causes such as tumors subdural hematomas poisoning or trauma and not considered Strokes so the difference between a stroke and a TI a or a transient ischemic attack is that a TI a is a brief episode of neurological dysfunction typically less than one hour but up to 24 hours with a vascular cause and with no evidence of infarction meaning cell death on Imaging they were previously distinguished by the duration of the neurological symptoms but now a distinguished based on the absence of in fact evidence on it Jing and resolution of symptoms the two main types of stroke ischemic stroke or hemorrhagic stroke with around 80% being ischemic an ischemic stroke is caused by the blockage of blood flow while a hemorrhagic stroke is caused by a rupture and extravasation of blood in the brain or surrounding tissue also note that Strokes with ischemic areas have a risk for breeding there for ischemic stroke can undergo what is known as a hammer dragic transformation there are four main mechanisms for an ischemic stroke the first is thrombosis which is divided into large and small vessel disease large vessel disease involves the common and internal carotid 's the vertebral arteries and The Circle of Willis the main causes of thrombi here include atherosclerosis vasoconstriction dissection and vasculitis small vessel disease involves smaller she's of The Circle of Willis and arteries in the distal vertebral and battler arteries causes here include lightbulb highly gnosis which is a build-up of fatty hyelin matter secondary to hypertension and aging as well as micro after ohms which is small atherosclerosis plaques thrombi can also be caused by Sickle Cell red blood cells clumping together and thrombi may also generate emboli which are the second mechanism for ischemic stroke the emboli are entities that travel in the blood and can be part of a thrombus that has been broken off they can be fat they can be air or even cancer or clumps of bacteria most commonly the source of the embolus is the heart due to atrial fibrillation atrial or ventricular thrombi rheumatic heart disease recent myocardial infarction or even recent coronary artery bypass grafting emboli may also travel from sources..." Learn more about your ad choices. Visit megaphone.fm/adchoices

References: Miles MVP, Beasley JR, Reed HE, Miles DT, Haiflich A, Beckett AR, Lee YL, Bowden SE, Panacek EA, Ding L, Brevard SB, Simmons JD, Butts CC. Overutilization of Helicopter Emergency Medical Services in Central Gulf Coast Region Results in Unnecessary Expenditure. J Surg Res. 2022 May;273:211-217. doi: 10.1016/j.jss.2021.12.038. Epub 2022 Jan 29. PMID: 35093837. Roman J, Shank W, Demirjian J, Tang A, Vercruysse GA. Overutilization of Helicopter Transport in the Minimally Burned-A Healthcare System Problem That Should Be Corrected. J Burn Care Res. 2020 Jan 30;41(1):15-22. doi: 10.1093/jbcr/irz143. PMID: 31504602. Adcock AK, Minardi J, Findley S, Daniels D, Large M, Power M. Value Utilization of Emergency Medical Services Air Transport in Acute Ischemic Stroke. J Emerg Med. 2020 Nov;59(5):687-692. doi: 10.1016/j.jemermed.2020.08.005. Epub 2020 Oct 1. PMID: 33011044; PMCID: PMC8006070. Chen X, Gestring ML, Rosengart MR, Peitzman AB, Billiar TR, Sperry JL, Brown JB. Logistics of air medical transport: When and where does helicopter transport reduce prehospital time for trauma? J Trauma Acute Care Surg. 2018 Jul;85(1):174-181. doi: 10.1097/TA.0000000000001935. PMID: 29787553. Chen X, Gestring ML, Rosengart MR, Billiar TR, Peitzman AB, Sperry JL, Brown JB. Speed is not everything: Identifying patients who may benefit from helicopter transport despite faster ground transport. J Trauma Acute Care Surg. 2018 Apr;84(4):549-557. doi: 10.1097/TA.0000000000001769. PMID: 29251708.

Contributor: Travis Barlock MD Educational Pearls:  Large Vessel Occlusion (LVO) is a condition where a clot blocks one of the major blood vessels in the brain, leading to a stroke. What are the vessels that can experience an LVO? Middle Cerebral artery (MCA) Internal Carotid Artery (ICA) Anterior Cerebral Artery (ACA) Posterior Cerebral Arteries (PCA) Basilar Artery (BA) Vertebral Arteries (VA) What are the locations at which a mechanical thrombectomy can be performed as a treatment for an LVO? Distal ICA, M1 or M2 segments of the MCA, A1 or A2 segments of the ACA, and some evidence for the BA. What are the symptoms of LVO? Use the mnemonic FANG-D to remember a few key symptoms: Field Cut (A person loses vision in a portion of their visual field) Aphasia (Difficulty speaking) Neglect (A person may have difficulty paying attention to or acknowledging stimuli on the affected side of their body or in their environment. For example, a person with neglect may deny that their left hand belongs to them) Gaze Deviation (One or both eyes are turned away from the direction of gaze) Dense Hemiparesis (Paralysis affecting one side of the body) What are the treatment windows for treating an LVO? 24 hours for mechanical thrombectomy 0-4.5 hours for tPA/TNK References 1. Brain embolism, Caplan LR, Manning W (Eds), Informa Healthcare, New York 2006. 2. Berkhemer OA, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015 Jan 1;372(1):11-20. doi: 10.1056/NEJMoa1411587. Epub 2014 Dec 17. Erratum in: N Engl J Med. 2015 Jan 22;372(4):394. PMID: 25517348. 3. Herpich, Franziska MD1,2; Rincon, Fred MD, MSc, MB.Ethics, FACP, FCCP, FCCM1,2. Management of Acute Ischemic Stroke. Critical Care Medicine 48(11):p 1654-1663, November 2020. 4. Warner JJ, Harrington RA, Sacco RL, Elkind MSV. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke. Stroke. 2019 Dec;50(12):3331-3332. doi: 10.1161/STROKEAHA.119.027708. Epub 2019 Oct 30. PMID: 31662117. 5. Hoglund J, Strong D, Rhoten J, Chang B, Karamchandani R, Dunn C, Yang H, Asimos AW. Test characteristics of a 5-element cortical screen for identifying anterior circulation large vessel occlusion ischemic strokes. J Am Coll Emerg Physicians Open. 2020 Jul 24;1(5):908-917. doi: 10.1002/emp2.12188. PMID: 33145539; PMCID: PMC7593424. Summarized by Jeffrey Olson | Edited by Meg Joyce & Jorge Chalit, OMS1  

Tenecteplase in Acute Ischemic Stroke  Special Guest: Salia Farrokh, PharmD, BCCCP, FNCS 07:45 – Alteplase history and comparison 14:20 – Thrombolysis guidelines in AIS 19:15 – Tips for reading stroke literature 21:00 – Tenecteplase literature review  39:45 – Tenecteplase research-in-progress 42:30 – Thrombolytic-induced ICH management 46:25 – Arguments for and against Tenecteplase 51:30 – Advice when switching thrombolytics 58:20 – Ultimate take-aways Reference List: https://pharmacytodose.files.wordpress.com/2023/04/tenecteplase-in-acute-ischemic-stroke-references.pdf PharmacyToDose.Com  @PharmacyToDose  PharmacyToDose@Gmail.com Learn more about your ad choices. Visit megaphone.fm/adchoices

In Part 3 of a 3-part series, Sunil A. Sheth, MD, discusses his article, "Mechanical Thrombectomy for Acute Ischemic Stroke" from the April Continuum Cerebrovascular Disease issue. This article and accompanying Continuum Audio interview are available to subscribers at continpub.com/MechThromb. This podcast is sponsored by argenx. Visit www.vyvgarthcp.com for more information.

In Part 2 of a 3-part series, Sunil A. Sheth, MD, discusses his article, "Mechanical Thrombectomy for Acute Ischemic Stroke" from the April Continuum Cerebrovascular Disease issue. This article and accompanying Continuum Audio interview are available to subscribers at continpub.com/MechThromb. This podcast is sponsored by argenx. Visit www.vyvgarthcp.com for more information.

In Part 1 of a 3-part series, Sunil A. Sheth, MD, discusses his article, "Mechanical Thrombectomy for Acute Ischemic Stroke" from the April Continuum Cerebrovascular Disease issue. This article and accompanying Continuum Audio interview are available to subscribers at continpub.com/MechThromb. This podcast is sponsored by argenx. Visit www.vyvgarthcp.com for more information.

Editor's Summary by Kirsten Bibbins-Domingo, PhD, MD, MAS, Editor in Chief of JAMA, the Journal of the American Medical Association, for the February 28, 2023, issue. Related Content: Audio Highlights

Geopolitiske spenninger har satt en stopper for videre forskning på SARS-CoV-2s opprinnelse. Men den gode nyheten er at under Kinas siste bølge av covid-19 har det ikke blitt funnet noen nye varianter av viruset. Hvordan sto det til med barns skjermbruk fra juni 2019 til august 2021? Hvordan påvirker såkalt longcovid sysselsettingen? Det foreligger dessuten nå mer forskning på dødelighet blant leger under pandemien. Åtte land har bekjempet en tropisk infeksjonssykdom i løpet av 2022. Du får også høre om forskning på brystkreft og på hjerneslag, og på effekten av treplanting i urbane områder for å senke temperaturen og dermed begrense hetebølger. Og har vi kommet ett skritt nærmere tankekontroll for pasienter med alvorlige lammelser – uten å operere inn implantater i hjernen? Sjefredaktør Are Brean deler siste nytt fra andre vitenskapelige tidsskrifter den siste tiden. Tilbakemeldinger kan sendes til stetoskopet@tidsskriftet.no.    Stetoskopet produseres av Synne Muggerud Sørensen, Sigurd Ziegler, Are Brean og Julie Didriksen ved Tidsskrift for Den norske legeforening. Ansvarlig redaktør er Are Brean.   Jingle og lydteknikk: Håkon Braaten / Moderne media   Coverillustrasjon: Stephen Lee   Artikler nevnt:   WHO abandons plans for crucial second phase of COVID-origins investigation Characterisation of SARS-CoV-2 variants in Beijing during 2022: an epidemiological and phylogenetic analysis - The Lancet Trends in Screen Time Use Among Children During the COVID-19 Pandemic, July 2019 Through August 2021 Excess Mortality Among US Physicians During the COVID-19 Pandemic Association of Post–COVID-19 Condition Symptoms and Employment Status Long COVID Linked With Unemployment in New Analysis Bird Flu Has Begun to Spread in Mammals—Here's What's Important to Know Eight countries eliminated a neglected tropical disease in 2022 Breast-Conserving Surgery with or without Irradiation in Early Breast Cancer Overcoming Resistance — Omission of Radiotherapy for Low-Risk Breast Cancer Endovascular Therapy for Acute Stroke with a Large Ischemic Region Improved Prospects for Thrombectomy in Large Ischemic Stroke Trial of Endovascular Thrombectomy for Large Ischemic Strokes Trial of Endovascular Therapy for Acute Ischemic Stroke with Large Infarct Cooling cities through urban green infrastructure: a health impact assessment of European cities Assessment of Safety of a Fully Implanted Endovascular Brain-Computer Interface for Severe Paralysis in 4 Patients: The Stentrode With Thought-Controlled Digital Switch (SWITCH) Study

Bradyarrhythmia during AF screening, thrombolysis in stroke, NP vs MD care, and the most biased paper this year — on LAAO — are the topics John Mandrola, MD, discusses in this week's podcast. This podcast is intended for healthcare professionals only. To read a partial transcript or to comment, visit: https://www.medscape.com/twic I. Screening with ILR - Ade Adamson Tweet https://twitter.com/AdeAdamson/status/1625878856820482048?s=20 - The Rapid Rise in Cutaneous Melanoma Diagnoses https://www.nejm.org/doi/full/10.1056/NEJMsb2019760 - Loop Trial https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01698-6/fulltext - Prevalence and Prognostic Significance of Bradyarrhythmias in Patients Screened for Atrial Fibrillation vs Usual Care https://jamanetwork.com/journals/jamacardiology/fullarticle/2801362 II. Thrombolysis in Mild Stroke Thrombolysis Not Necessary in Mild Nondisabling Stroke: ARAMIS https://www.medscape.com/viewarticle/988381 - PRISMS Trial https://jamanetwork.com/journals/jama/fullarticle/2687354 - Risk of selection bias assessment in the NINDS rt-PA stroke study https://pubmed.ncbi.nlm.nih.gov/35705913/ - Tissue Plasminogen Activator for Acute Ischemic Stroke https://www.nejm.org/doi/full/10.1056/NEJM199512143332401 - Effects of alteplase for acute stroke; Hacke et al meta-analysis https://journals.sagepub.com/doi/10.1177/1747493017744464 - Methodological survey of missing outcome data in an alteplase for ischemic stroke meta-analysis https://onlinelibrary.wiley.com/doi/full/10.1111/ane.13656 - ECASS; Thrombolysis with Alteplase 3 to 4.5 Hours after Acute Ischemic Stroke https://www.nejm.org/doi/full/10.1056/nejmoa0804656 - Thrombolysis with alteplase 3-4.5 hours after acute ischaemic stroke: trial reanalysis adjusted for baseline imbalances https://pubmed.ncbi.nlm.nih.gov/32430395/ III. NP vs MD Care This Doc Still Supports NP/PA Led Care ... With Caveats https://www.medscape.com/viewarticle/967073 - The Productivity of Professions: Evidence from the Emergency Department https://www.nber.org/papers/w30608 - Independent Nurse Practitioners and Physician Assistants: A Doc's View https://www.medscape.com/viewarticle/924047 IV. LAAO vs OAC - Comparative Effectiveness of Left Atrial Appendage Occlusio Versus Oral Anticoagulation by Sex https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.122.062765 You may also like: Medscape editor-in-chief Eric Topol, MD, and master storyteller and clinician Abraham Verghese, MD, on Medicine and the Machine https://www.medscape.com/features/public/machine The Bob Harrington Show with Stanford University Chair of Medicine, Robert A. Harrington, MD. https://www.medscape.com/author/bob-harrington Questions or feedback, please contact news@medscape.net

In this week's episode, we'll discuss involvement of IL-13 and IL-4 signaling in fibrotic progression of myelofibrosis; next, we review results on a novel agent using vWF-dependent mechanisms to lyse pathological thrombi in acute ischemic stroke. Finally, we'll shed new light on findings that implicate the GARP-TGF-beta-1 pathway in the loss of natural killer cell cytotoxicity in relapsed AML.

In this podcast, JNIS Editor-in-Chief, Dr. Felipe C. Albuquerque, speaks with Dr. Krishna C. Joshi(1) and Dr. Michael Chen(2) about their paper "Endovascular thrombectomy for acute ischemic stroke in patients with cancer: a propensity-matched analysis" - https://jnis.bmj.com/content/14/12/1161. Please subscribe to the JNIS Podcast via all podcast platforms, including Apple Podcasts, Google Podcasts, Stitcher and Spotify, to get the latest episodes. Also, please consider leaving us a review or a comment on the JNIS Podcast iTunes page: https://podcasts.apple.com/gb/podcast/jnis-podcast/id942473767 Thank you for listening! This episode was edited by Brian O'Toole. (1) Neurological Surgery, Rush University Medical Center, Chicago (2) Neurological Surgery, Rush University Medical Center, Chicago

Commentary by Dr Andy Lee

Today let's talk a little about some considerations for the patient presenting with an acute ischemic stroke.  I've got a couple of references for you below as well!Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Updatehttps://www.ahajournals.org/doi/10.1161/STR.0000000000000211The Code Stroke Handbook: Approach to the Acute Stroke Patienthttps://www.amazon.com/Code-Stroke-Handbook-Approach-Patient/dp/0128205229/ref=sr_1_6?crid=3C5STQ82E9UYW&keywords=acute+stroke+hand&qid=1668425511&sprefix=acute+stroke+hand%2Caps%2C92&sr=8-6&ufe=app_do%3Aamzn1.fos.18ed3cb5-28d5-4975-8bc7-93deae8f9840 Find me on Twitter @Drkentris (https://twitter.com/DrKentris) Email me at theneurotransmitterspodcast@gmail.com https://linktr.ee/DrKentris The views expressed do not necessarily represent those of any associated organizations. The information in this podcast is for educational and informational purposes only and does not represent specific medical/health advice. Please consult with an appropriate health care professional for any medical/health advice.

Dr. Jonathan M. Coutinho discusses his paper, "Diagnostic Yield of ECG-gated Cardiac CT in the Acute Phase of Ischemic Stroke vs Transthoracic Echocardiography". Show references: https://n.neurology.org/content/early/2022/08/01/WNL.0000000000200995 This podcast is sponsored by argenx. Visit www.vyvgarthcp.com for more information.

Date: September 20th, 2022 Reference: Menon et al. Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial. The Lancet 2022 Guest Skeptic: Professor Daniel Fatovich is an emergency physician and clinical researcher based at Royal Perth Hospital, Western Australia. He is Head of the Centre […]

Dr. Dan Ackerman talks with Dr. Jonathan Coutinho about ECG-gated cardiac CT in the acute phase of ischemic stroke vs. thransthoracic echocardiography. Read the full article in Neurology. This podcast is sponsored by argenx. Visit www.vyvgarthcp.com for more information.

In this episode of the podcast, we discuss the management of Acute Ischemic Stroke (AIS). Our guest is Dr. Fred Rincon, a neurologist and critical care specialist with expertise in the resuscitation and management of acute brain injured patients. He is a Professor of Neurology at Cooper Medical School of Rowan University and Director of the Neuro-ICU at Cooper University Health Care in Camden, New Jersey. Additional Resources Management of Acute Ischemic Stroke. F. Herpich and F. Rincon: https://pubmed.ncbi.nlm.nih.gov/32947473/ AHA Guidelines for the Management of Acute Ischemic Stroke (2019): https://pubmed.ncbi.nlm.nih.gov/31662037/ Link to NIHSS Certification Course: https://www.nihstrokescale.org/ The intensive care management of acute ischemic stroke. D. Sharma and M. Smith: https://pubmed.ncbi.nlm.nih.gov/35034076/ Association of Neurocritical Care Services with Mortality and Functional Outcomes for Adults With Brain Injury. Meta-analysis. JAMA Neurology 2022: https://pubmed.ncbi.nlm.nih.gov/36036899/ Book Recommendations: The Servant: A Simple Story of About the True Essence of Leadership. By James C. Hunter: https://amzn.to/3U6u6SI How to Be a Leader: An Ancient Guide to Wise Leadership. By Plutarch: https://amzn.to/3eMBxhU

As we see more patients who have had Covid-19, we ask psychiatrist, Dr. Imaan Alaidroos, to speak with us about the neuropsychiatric impact of the disease. In this episode, Dr. Alaidroos outlines the treatments that are currently being studied for the neuropsychiatric symptoms of Covid-19. We also chat about the implications of these symptoms for the field of mental health. Hosts: Alan, Toshia Guest: Imaan Alaidroos, MD References: 7. Qureshi, A. I., Baskett, W. I., Huang, W., Shyu, D., Myers, D., Raju, M., Lobanova, I., Suri, M., Naqvi, S. H., French, B. R., Siddiq, F., Gomez, C. R., & Shyu, C. R. (2021). Acute Ischemic Stroke and COVID-19: An Analysis of 27 676 Patients. Stroke, 52(3), 905–912. https://doi.org/10.1161/STROKEAHA.120.031786 8. Helms J, Kremer S, MerdjiH, Clere-JehlR, Schenck M, KummerlenC, et al. Neurologic features in severe SARS-CoV-2 infection. N EnglJ Med. 2020;382:2268–2270. doi: 10.1056/NEJMc2008597. 9. FerrandoSJ, KlepaczL, Lynch S, TavakkoliM, DornbushR, BaharaniR, Smolin Y, Bartell A. COVID-19 psychosis: a potential new neuropsychiatric condition triggered by novel coronavirus infection and the inflammatory response? Psychosomatics. 2020;61:551–555. doi: 10.1016/j.psym.2020.05.012. 10. Parra A, JuanesA, LosadaCP, Álvarez-SesmeroS, Santana VD, Martí I, et al. Psychotic symptoms in COVID-19 patients. A retrospective descriptive study. Psychiatry Res. 2020;291:113254. doi: 10.1016/j.psychres.2020.113254. 11. Farooq, S., Tunmore, J., Wajid Ali, M., & Ayub, M. (2021). Suicide, self-harm and suicidal ideation during COVID-19: A systematic review. Psychiatry research, 306, 114228. https://doi.org/10.1016/j.psychres.2021.114228 12. Stefano, G. B., Büttiker, P., Weissenberger, S., Ptacek, R., Wang, F., Esch, T., Bilfinger, T. V., & Kream, R. M. (2021). Biomedical Perspectives of Acute and Chronic Neurological and Neuropsychiatric Sequelae of COVID-19. Current neuropharmacology, 10.2174/1570159X20666211223130228. Advance online publication. https://doi.org/10.2174/1570159X206662112231 13. de Erausquin, G. A., Snyder, H., Carrillo, M., Hosseini, A. A., Brugha, T. S., Seshadri, S., & CNS SARS-CoV-2 Consortium (2021). The chronic neuropsychiatric sequelae of COVID-19: The need for a prospective study of viral impact on brain functioning. Alzheimer's & dementia : the journal of the Alzheimer's Association, 17(6), 1056–1065. https://doi.org/10.1002/alz.12255 14. PashaeiY. Drug repurposing of selective serotonin reuptake inhibitors: Could these drugs help fight COVID-19 and save lives? J. Clin. Neurosci. 2021;88:163–172. doi: 10.1016/j.jocn.2021.03.010. 15. Dąbrowska, E., Galińska-Skok, B., & Waszkiewicz, N. (2021). Depressive and Neurocognitive Disorders in the Context of the Inflammatory Background of COVID-19. Life (Basel, Switzerland), 11(10), 1056. https://doi.org/10.3390/life11101056 Kępińska AP, Iyegbe CO, Vernon AC, Yolken R, Murray RM, Pollak TA. Schizophrenia and Influenza at the Centenary of the 1918-1919 Spanish Influenza Pandemic: Mechanisms of Psychosis Risk. Front Psychiatry. 2020 Feb 26;11:72. doi: 10.3389/fpsyt.2020.00072. PMID: 32174851; PMCID: PMC7054463.

Editor's Summary by Kirsten Bibbins-Domingo, PhD, MD, MAS, Editor in Chief of JAMA, the Journal of the American Medical Association, for the August 16, 2022 issue.

Dr. James Braun, Neurosciences Pharmacy Clinical Specialist at SSM Health St. Louis, and Dr. Kyle Hoelting, Senior Manager of Drug Information at Vizient, continue to share their insights on the use of TNK vs Alteplase for treating acute ischemic stroke. They also discuss the nuances of this therapeutic area and share recent work from an expert panel led by Vizient.   Guest speakers: James Braun, PharmD, BCCCP Neurosciences Pharmacy Clinical Specialist  SSM Health   Kyle Hoelting, PharmD, BCPS Senior Manager of Drug Information  Vizient   Moderator: Gretchen Brummel, PharmD, BCPS Pharmacy Executive Director Vizient Center for Pharmacy Practice Excellence   Show Notes: [00:30-3:59] Medication safety risks associated with thrombolytics [04:00-4:42] Using one drug over another [04:43-6:48] How frontline pharmacy staff can utilize this information [06:49-11:44] What Vizient can add to the discussion [11:45-11:55] When report will be released   Links | Resources: Tenecteplase vs alteplase in acute ischemic stroke: Vizient expert panel Verified Rx: Evidenced based medicine Click here Verified Rx: Show me the data! Updates on the evidence of thrombolytic use in ischemic strokes Click here Verified Rx: Information overload: tips and tricks for staying on top of the literature, part 1 Click here Verified Rx: Information overload: tips and tricks for staying on top of the literature, part 2 Click here   Subscribe Today! Apple Podcasts Amazon Podcasts Google Podcasts Spotify Stitcher Android RSS Feed

On Episode 18 of the Stroke Alert Podcast, host Dr. Negar Asdaghi highlights two articles from the July 2022 issue of Stroke: “Impact of Shunting Practice Patterns During Carotid Endarterectomy for Symptomatic Carotid Stenosis” and “Socioeconomic Inequalities in Reperfusion Therapy for Acute Ischemic Stroke.” She also interviews Dr. Magdy Selim about his article “Effect of Deferoxamine on Trajectory of Recovery After Intracerebral Hemorrhage: A Post Hoc Analysis of the i-DEF Trial.” Dr. Negar Asdaghi:         Let's start with some questions. 1) Is deferoxamine mesylate yet another failed agent for treatment of patients with intracerebral hemorrhage, or is deferoxamine getting us closer than ever to an approved therapy for this deadly form of stroke? 2) Are different strokes happening to different folks due to their disadvantaged socioeconomic status? 3) And finally, how does a surgeon's personal practice preference to either routinely or selectively use carotid shunting during carotid endarterectomy impact the recurrent risk of stroke or death in patients with symptomatic carotid disease? We'll tackle these questions and a lot more in today's podcast as we continue to cover the cerebrovascular world's latest and greatest because, without a doubt, this is the best in Stroke. Dr. Negar Asdaghi:         Welcome back to the July issue of the Stroke Alert Podcast. My name is Negar Asdaghi. I'm an Associate Professor of Neurology at the University of Miami Miller School of Medicine and your host for the monthly Stroke Alert Podcast. The July 2022 issue of Stroke contains a range of really interesting papers that I'd like to highlight here. As part of our Cochrane Corner articles, giving us short summaries of the long systematic review of a given topic, we have two short articles, one on the issue of local versus general anesthesia for carotid endarterectomy, where we learn that based on the current evidence, there's no convincing difference between local versus general anesthesia in the risk of stroke and death within 30 days after the procedure. In the second Cochrane Corner article, titled "Information Provision for Stroke Survivors and Their Carers," we learn that stroke survivors and their caregivers routinely report dissatisfaction with information provided to them by their clinicians about their condition and how active approaches to information provision is superior to its passive forms in improving patients' involvement in their care, their satisfaction, and, ultimately and not surprisingly, their stroke outcome. Dr. Negar Asdaghi:         As part of our original contributions in this issue of the journal, we have an important paper titled "The Risk of Early Versus Later Rebleeding From Dural AV Fistulas With Cortical Venous Drainage." We are reminded in this paper that cranial dural arteriovenous fistulas are classified based on their venous drainage into those with or those without cortical venous drainage, or CVD. Dural AV fistulas without CVD rarely cause intracranial bleeding, while those with CVD may cause hemorrhage. In this study, the authors show that the risk of rebleeding of dural AV fistulas with CVD presenting with hemorrhage is increased in the first two weeks after ICH, emphasizing the importance of early detection of these malformations by vascular imaging and early treatment of AV fistulas with cortical drainage. This paper is another analysis from the CONDOR registry. Our devoted Stroke Alert listeners recall that we covered this registry in more detail when we interviewed Dr. Amin-Hanjani last October on the outcomes of intracerebral hemorrhage patients found to have dural AV fistulas. I encourage you to review these articles in addition to listening to our podcast today. Dr. Negar Asdaghi:         Later in the podcast, I have the distinct honor of interviewing Dr. Magdy Selim from Harvard Medical School on a critical analysis from i-DEF trial to examine the long-term outcome of patients with ICH who were randomized to receive deferoxamine versus placebo. As an expert in the field of intracerebral hemorrhage and a member of the recently published American Heart Association Guidelines Committee, Dr. Selim was not fazed at all about the neutral results of the trial. "The future of ICH is bright," he says, and in the interview, he tells us why. But first, with these two articles. Dr. Negar Asdaghi:         Since its first reported successful surgery in 1953, carotid endarterectomy, or CEA, has become a common surgical procedure to prevent ischemic stroke in patients with carotid disease. CEA requires a temporary clamping of the carotid artery that is being worked on. During this time, the ipsilateral hemisphere is, of course, dependent on collateral flow from the posterior circulation or from the contralateral anterior circulation to maintain its perfusion pressure. Intraoperatively, various methods are used to monitor cerebral perfusion, and the risk of clamping-induced hypoperfusion is obviously variable for each patient depending on the patient's specific anatomy, their collateral status, and other risk factors. One way to protect the brain against possible clamp-induced ischemia is to do carotid shunting. The problem is that carotid shunting also comes with its own set of risks and problems. There's the risk of causing carotid dissection, embolization of pieces of the plaque during shunt insertion, or the risk of causing air embolism. Dr. Negar Asdaghi:         There are also other shunt-related local complications that should be noted, such as possibility of causing injuries to the cranial nerves or development of neck hematoma related to the more extensive surgical exposure required for shunting. So, it's not surprising that the practice patterns with regards to shunting is quite variable amongst different surgeons. There are surgeons that are considered routine shunters, and those who are considered selective shunters, meaning that the shunt is inserted only in cases with a particular indication. The question is whether the surgeon's preference for shunting can impact the CEA outcomes. In the current issue of the journal, we have an interesting study led by Dr. Randall DeMartino from the Division of Vascular and Endovascular Surgery at Mayo Clinic, Rochester, where the authors look at the impact of shunting practice patterns during carotid endarterectomy on the following post-CEA outcomes: number one, in-hospital stroke and in-hospital death rates, and number two, combined stroke and death in patients with a recent symptomatic carotid disease, that is, carotid stenosis associated with a history of either ipsilateral stroke or TIA within the past 14 days of endarterectomy. Dr. Negar Asdaghi:         So, the data for the study came from the ongoing Vascular Quality Initiative database, which comprises a network of more than 600 North American academic and community hospitals, and collects data on 12 different vascular procedures, one of which is CEA. The study included over 13,000 carotid endarterectomies performed from 2010 to 2019 for symptomatic carotid patients. This number came after they applied their exclusion criteria to all CEAs performed in the database during this timeframe, importantly excluding any asymptomatic carotid surgeries or those in whom surgery was performed after the two-week mark post qualifying TIA or stroke. Now, before we go over the results, let's go over some definitions used in the study. They had to classify surgeons to be able to do the study into two categories of routine versus selective shunters. So, what they did was to analyze all consecutive CEAs, whether they were done on symptomatic or asymptomatic carotids, in this database, aggregated at the surgeon level. Surgeons routinely shunting in over 95% of their procedures were gauged as routine shunters. Otherwise, they were classified as selective shunters. Dr. Negar Asdaghi:         Now, coming to each case included in this study, each surgical case was, in turn, classified into four categories based on whether or not a shunt was actually used for that particular case: category one, no shunt used; category two, shunt used as a routine procedure; number three, shunt used for a preoperative, mostly anatomical indication; number four, shunt was used for an intraoperative indication, which, as we mentioned before, these are mostly intraoperative hemodynamic compromised situations. And here are the results: In total, 3,186 of surgeries, that is 24% of surgeries, were performed by routine shunters versus 76% by selective shunters. So, most surgeons were selective shunters in this study. The demographic of patients operated by the routine versus selective shunters were more or less similar with regards to the age of the patients, most of their vascular risk factors, and the degree of ipsilateral or contralateral carotid stenosis or occlusion, with a few notable exceptions, in that patients undergoing surgery by routine shunters were more likely White, more likely to have had a prior CABG, more likely to undergo the operation while taking a P2Y12 inhibitor antiplatelet agent, and these patients were more likely to have had a TIA rather than a stroke as their qualifying event, which probably explains why they were more likely to be operated on within 48 hours of symptom onset as well. So, the authors accounted for these differences when they did their multivariate analysis. Dr. Negar Asdaghi:         The other thing to note was that overall, routine shunters used a shunt in 98.1% of their cases, whereas selective shunters used them in 46% of their cases. Now, in terms of their study outcomes, the shunting practice pattern did not impact the primary outcomes of in-hospital stroke or death, or a combination of these two outcomes, or even the odds of development of cranial nerve injuries or hemorrhage in the adjusted model, which is really good news here. But interestingly, in the final adjusted model, whether or not an actual shunt was placed during surgery did significantly increase the risk of postoperative stroke, with the odds ratio of 1.29, an effect that was entirely driven by the use of shunt by a surgeon classified as a selective shunter in this study. Dr. Negar Asdaghi:         So, in simple terms, if a shunt was placed during CEA, it did increase the risk of stroke only if that surgeon was a selective shunter. Another interesting association was that amongst selective shunters, placing a shunt for a patient with a very recent ischemic event, that is, TIA or stroke within the past 48 hours prior to surgery, and placing a shunt for an intraoperative indication, meaning shunt placement was not pre-surgically planned, also significantly increased the risk of postoperative stroke. So, what we learned from the study is that, though a surgeon's shunting practice pattern did not have an impact on the overall postoperative risk of stroke or death, the placement of a shunt did indeed increase the risk of postoperative stroke only if it was placed by a surgeon who is a selective shunter, especially for an intraoperative indication in a patient with a recent ischemic event. Dr. Negar Asdaghi:         So, shunts can be tricky, especially if they're done by a surgeon who doesn't place them routinely. So, my take-home message is that ultimately, like every other procedure in medicine, clinical outcomes are as much operator dependent as they are patient dependent, and for every procedure, it's fair to say that practice makes perfect. Dr. Negar Asdaghi:         It is now more than 25 years since intravenous thrombolytic therapy has been approved for treatment of patients with acute ischemic stroke and more than seven years since randomized control trials demonstrated the efficacy of mechanical thrombectomy to improve clinical outcome in ischemic stroke patients with large vessel occlusions. To date, reperfusion therapies are the only available acute treatments for select patients with ischemic stroke. What do we mean by "select"? "Select" meaning that not all patients will benefit from these therapies, making it absolutely necessary for clinicians to be up to date with various indications and contraindications to use these therapies. Needless to say that the criteria for reperfusion therapies do not and should not consider the socioeconomic status of patients, but sadly, socioeconomic inequalities seem to impact the use of reperfusion therapies. Dr. Negar Asdaghi:         In this issue of the journal, in the study titled "Socioeconomic Inequalities in Reperfusion Therapy for Acute Ischemic Stroke," Dr. Øgendahl Buus from Aarhus University Hospital in Denmark and colleagues studied the impact of the socioeconomic status of stroke patients on the odds of receiving reperfusion therapies in the large nationwide Danish Stroke Registry, or DSR. Now a bit about the registry: DSR contains prospectively collected nationwide data on all stroke patients admitted to Danish hospitals. It's interesting to note that in Denmark, stroke patients are exclusively admitted to public hospitals, and all departments treating stroke patients are obligated to report data to DSR. Now, for this study, they included over 63,000 stroke patients from 2013 to 2018. After excluding hemorrhagic stroke, TIAs, and other exclusion criteria of the study, they arrived at their sample size of 37,187 patients that were included in this study. Dr. Negar Asdaghi:         Now, a few definitions. The socioeconomic status of each patient was determined based on three parameters. Parameter number one, their educational level. It was categorized into three levels of low, medium, or high levels of education. Category number two, income level. This was calculated based on the average family equivalent disposable income, or FED income, during five years prior to stroke onset, again classified into three categories of high, medium, or low income. And the third factor was the employment status of the patient during the calendar year prior to the stroke onset, also categorized into three categories of employed, unemployed, and retired. And, of course, the authors used various definitions to be able to fit special situations into these categories. For instance, a person who is temporarily unemployed due to illness or other special situation was still categorized under the employed category. So, that gave them, in total, nine groups to analyze across these three categories. Dr. Negar Asdaghi:         And here are their findings. The median age of total stroke patients in the cohort was 73.2 years, 44.1% were women, 41% categorized under low educational level, 68% retired, and 33.3% had low income levels. Not surprisingly, patients and hospital characteristics varied tremendously across these nine groups of education, employment, and income, and a univariate analysis in general, low socioeconomic status was associated with more severe strokes, living alone, living at an assisted living residency, having had prior stroke, high comorbidity index score, hypertension, and late hospital arrival. So, they accounted for these differences in their multivariate analysis. Dr. Negar Asdaghi:         Now, overall, the treatment rates of IV thrombolysis was 17.6%, which is actually considered a very high percentage as compared to other registry-based studies, but the percentage of IV thrombolytic use dramatically varied based on the different socioeconomic designation. So, let's look at this. In the univariate analysis, for education, intravenous thrombolysis rates were 19.3% among patients with high educational level compared to 16.2% among patients with low educational level. Let's look at income. For income, IV thrombolytic treatment rates reach 20.7% for high-income patients compared to 14.8% for low-income patients. For employment status, thrombolytic rates were 23.7% among employed patients compared to 15.7% for unemployed patients. In their fully adjusted models, unemployed patients were less likely to receive IV lytics as compared to their employed counterparts. Dr. Negar Asdaghi:         Now, for thrombectomy, socioeconomic gradients were also noted for these three categories. For education, thrombectomy rates were 4.5% among patients with high education level compared to 3.6% among patients with low educational level. For income, treatment rates were 3.2% among low-income patients compared to 4.7% among high-income patients. But arguably, the most robust differences were noted again across the category of employment. Employed patients were nearly twice more likely to receive thrombectomy as compared to unemployed patients, rates being 5.1% versus 2.8%, respectively. Now, when they adjusted their analysis to only those patients presenting within the reperfusion time windows in the fully adjusted models, unemployment and low income remain significant negative predictors of receiving both of these reperfusion therapies. So, what we learned from this study is that stroke patients who were unemployed, earned a relatively low income, or had fewer years of formal education were less likely to receive life-saving reperfusion therapies despite potentially being eligible for these treatments. Dr. Negar Asdaghi:         Now, let's take a moment to really understand that data presented here are in the context of a tax-funded, universal healthcare offered across Denmark, where we can at least make the assumption that financial constraints potentially preventing access to therapies are likely minimized. There are many countries around the globe where patients or family members have to pay for these therapies before even receiving them. So, these findings from the current study from Denmark are alarming in that they point to possibly more robust inequalities across the globe in other healthcare systems. Dr. Negar Asdaghi:         Intracerebral hemorrhage, or ICH, is an aggressive form of stroke, typically carrying a higher morbidity and mortality than its ischemic counterpart. Yet much of the research in the field of intracerebral hemorrhage has followed the ischemic stroke footsteps, including defining the optimal primary outcome for the randomized trials of ICH. For ischemic stroke, the 90-day functional outcome, as measured by the modified Rankin Scale, is commonly used as a primary outcome in clinical trials. There are many reasons for this selection, including the ease of use and the fact that the majority of functional recovery post-ischemic stroke occurs during the first 90-day time period. But time to maximum recovery and, importantly, the trajectory of recovery may be different in hemorrhagic as compared to ischemic stroke. Defining the long-term outcomes and longitudinal trajectory of recovery in ICH is, therefore, important to better understand its prognosis and, of course, selecting the appropriate primary outcome measure for future randomized trials of ICH. Dr. Negar Asdaghi:         In the recent years, the safety and efficacy of various agents to improve ICH outcomes have been tested. Deferoxamine mesylate, an iron-chelating agent, is one such agent that was recently studied as part of the i-DEF multicenter randomized trial, and the main results of the study were published in Lancet Neurology in 2019. In the current issue of the journal, in the study titled "Effect of Deferoxamine on Trajectory of Recovery After Intracerebral Hemorrhage," we learn about the results of a post hoc analysis of i-DEF that looks at the trajectory of functional outcome in patients enrolled in the trial with a special attention on their continued recovery after the 90-day post-ICH mark. Dr. Negar Asdaghi:         Joining me now is the senior author of this paper, Dr. Magdy Selim, who's also one of the primary investigators of i-DEF trial. Dr. Selim is a Professor of Neurology at Harvard Medical School and Chief of Stroke Division at Beth Israel Deaconess Medical Center in Boston. He's a world renowned researcher in the field of cerebrovascular disorders with special focus on treatment of patients with intracerebral hemorrhage. Dr. Selim has led and currently leads multiple National Institutes of Health-funded clinical trials of intracerebral hemorrhage, including the ongoing SATURN trial. I'm delighted to welcome him to our podcast today. Good afternoon, Magdy. Thank you for joining us today. Dr. Magdy Selim:             Thank you, Dr. Asdaghi. It's really my pleasure to be here with you, and I'm certainly honored to do this today. Dr. Negar Asdaghi:         That's great. Thank you. So, let's start with some background on deferoxamine and the literature supporting the use of deferoxamine before i-DEF. Dr. Magdy Selim:             So, as you mentioned, deferoxamine is an iron chelator; it binds to iron and removes excess iron from the body. The unique thing about it is that it has other neuroprotective properties, which are good for hemorrhagic stroke and ischemic stroke. It also has anti-inflammatory and anti-apoptotic effects. It even lowers the blood pressure, which we know sometimes is helpful in intracerebral hemorrhage. The rationale behind this or why this would be effective really comes from animal studies. After you have a hemorrhage, there is hemolysis of the red blood cells, there is a release of hemoglobin degradation products, in particular, iron, and the accumulation of iron in the hematoma and the surrounding tissue triggers a cascade of molecular and cellular events that lead to what we call secondary injury, characterized by inflammation, hydroxyl radical formation, and cell death. And many animal studies, animal models of intracerebral hemorrhage, whether in pigs or in rats, young or aged rats, have shown that treatment with deferoxamine can reduce iron in the brain after intracerebral hemorrhage and also results in improved performance on behavioral tests. And that was the reason why we moved into clinical testing. Dr. Negar Asdaghi:         So, a lot of encouraging data before the trial. Can we hear a little bit about the trial, its design, and inclusion criteria, please? Dr. Magdy Selim:             Sure. So i-DEF was a phase 2 study, and actually it started as Hi-DEF, which was high dose deferoxamine, and then became i-DEF, which intermediate dose deferoxamine. So, it's a randomized, double blind, placebo control trial. We used something called futility design, which is actually sort of new in the stroke field. And we had 294 patients who had supratentorial hemorrhage that were randomized within 24 hours to either get placebo or deferoxamine. And deferoxamine initially was given at 62 mg per day for three days, but then we ran into some safety issues with this high dose, and that's why we lowered it to 32, and that became the intermediate dose, or the i-DEF. So, the only kind of thing unique about inclusion/exclusion criteria was that there was an age cutoff, patients had to be 80 or younger. They needed to have some deficit on the exam, so their NIH Stroke Scale had to be 6 or greater, and their GCS had to be greater than 6, and their modified Rankin before the onset of the hemorrhage had to be less than 1. Dr. Negar Asdaghi:         And so, what were the primary and secondary outcomes in i-DEF? Dr. Magdy Selim:             The primary outcome was twofold actually. One of them was safety. One of the issues we ran into with the high dose is that the drug is associated with increased risk for adult respiratory distress syndrome, ARDS. So, we wanted to make sure that this lower dose was safe, and it does not increase the instance of ARDS. The second thing was, as I said, we used something called the futility design, and we wanted to compare the outcome of patients treated with deferoxamine versus placebo to determine whether it's futile to move to a large phase 3 trial or not. And what we were looking at is a difference in outcome and modified Rankin 0 to 2 at 90 days, and the difference would be at least 12% in favor of deferoxamine in order for us to move forward. You asked about the secondary outcomes as well? Dr. Negar Asdaghi:         Yes. Dr. Magdy Selim:             So, actually, the secondary outcomes, they're relevant because they're relevant to the study that we just published. So, the secondary outcomes was also to look at modified Rankin 0 to 3, instead of 0 to 2, at 90 days and the difference between the two treatment groups. We wanted to look at the ordinal distribution of the Rankin at the same time point. And we also wanted to look at all the outcomes at six months, 180 days. And that came a little bit later in the course of the study because there was some evidence emerging at that time that maybe assessment of outcome later in intracerebral hemorrhage would be more accurate than assessing it early on. Dr. Negar Asdaghi:         So, I want to come back to the secondary outcome, of course, that's sort of the topic of your current paper in this issue of the journal, but can you just briefly tell us, please, the primary outcome and the sort of results of what was published in 2019 with i-DEF before we move on to the current paper? Dr. Magdy Selim:             Yeah. So, as I said, the primary outcome was the difference in the proportion of patients that achieved modified Rankin 0 to 2 at 90 days, and what we wanted to see is a difference of around 12%. Unfortunately, the primary outcome was neutral, we did not see that. But what we saw actually, almost all the secondary outcomes were positive, except for the primary outcome. So, when we looked at the secondary outcome using modified Rankin 0 to 3, instead of 0 to 2, the difference was 12.1%. When we looked at the difference in the modified Rankin 0 to 2 at six months, the difference was 15.6% in favor of deferoxamine, but these were secondary outcomes and not the primary outcomes. Dr. Negar Asdaghi:         So, the trial is almost positive. It just depends on how you define the primary outcome, which is really a nice segue to your current study. In the current study, you looked at this secondary outcome in a longitudinal way and looked at the mRS of 0 to 2 at six months from ICH. Can you please tell us about this current paper? Dr. Magdy Selim:             Yeah. So, one of the things that we did with i-DEF is that we were checking the modified Rankin at different time points for all the patients. So, we had it after one week, after one month, after two months, after three months, and after six months. And what we wanted really was a couple of things, just in patients with intracerebral hemorrhage without any treatment, what's the natural course of recovery? And the interesting thing we found out is that patients actually continue to improve over time, and that's what you expect, but what we didn't expect is that they even continue to improve after 90 days. Dr. Magdy Selim:             We always used to think that maximum recovery is around 90 days from ischemic stroke literature, but we saw a lot of patients getting better after 90 days. And this turns out to be also the case with deferoxamine, but the interesting thing is that the percentage of patients that had a good outcome, modified Rankin 0 to 2, was higher with deferoxamine at day seven, at day 30, at day 60, not at 90 days, but again at six months. So, actually, it was higher at all time points except our primary endpoint. Dr. Negar Asdaghi:         So, Magdy, you've already answered my next question, which is exactly what you alluded to, deferoxamine seemed to have improved the outcomes at all of those time points, except for the 90 day, which was the primary outcome of your trial. Why do you think the magic was lost at 90 days? Dr. Magdy Selim:             This is really the million-dollar question. I think we obviously struggled over this. And we went back, we thought maybe there was misrating of the modified Rankin in some of the patients. We tried to correct for this. The difference was bigger, but still not significant. So, we don't really have a good reason to tell you why, at this particular time point, we didn't see the difference except bad luck, I think. But I mean, there are reasons, I think, the question that people actually ask me is the opposite, is why do you think a drug that you give for three days early on is going to make a difference after six months? And I think there are biological reasons to explain this. Dr. Magdy Selim:             So, what happened is that those hemorrhage patients have a lot of other problems. They have increased ICP, they have hydrocephalus, they have intraventricular hemorrhage, and actually iron has been implicated in the development of hydrocephalus in chronic white matter injury. So, my explanation is that you start early on with the treatment, it does help, but it takes a while for it to kick in and for this kind of medical complication to resolve until actually you see the true effect of the drug. And maybe that's why you see the unmasking at the end between the two groups. Dr. Negar Asdaghi:         Yeah, I think I want to recap this for our listeners. Very important to, again, think about those things that some of the acute therapies that we offer the patients may not have a measurable improvement outcome difference early on, certainly with intravenous thrombolysis, we saw that, whereas we saw measurable outcome difference at 90 days, or maybe in this case at six months, but not quite early on. So, it doesn't mean that they don't work. We just are unable to measure that difference and improvement early on. So, what do you think the future holds for deferoxamine? Are we going to see another trial? Dr. Magdy Selim:             Well, I certainly hope so. We're working on some few ideas for that. A lot of people think that maybe we should just do the same thing, but look at six months as the primary outcome. But I think we're actually, that's probably not our primary thinking at this point in time. So, we have published other papers, other analysis, to show that the effect of deferoxamine actually relates to the volume of the hemorrhage. So, if the hemorrhage is very small, there is very minimal benefit. If the hemorrhage is very large, also there is very minimal benefit. And that's really to get kind of the big bang for your buck. You really want people who have mild-to-moderate size hemorrhages. So, we're thinking of a couple of ways to go about deferoxamine with this, whether alone or in combination with other interventions. So, hopefully, we'll have some stuff to share with you in the coming few years, two or three. Dr. Negar Asdaghi:         We'll definitely look forward to reading about those or being involved in the trials as a site, but there's a great way of just actually talking about my next question. It's just completely different than the current paper. I wanted to digress a bit and talk about the recently published intracerebral hemorrhage guidelines, which just published a few months ago. You were part of the guidelines committee. Can you give us a little bit of your point of view of what are the top two most important updates from the guidelines in ICH treatment? Dr. Magdy Selim:             Actually, the guidelines, for the first time this year, in the first page, they have the top 10 take-home messages or top 10 new ones. So, in my opinion, the most important ones, we usually tell you what to do, but here we tell you what not to do because we think it's not good for the patients. So, for example, using steroids just as a prophylactic therapy is actually not recommended. The same thing, we see a lot of people put patients with hemorrhage on hypertonic saline, hyperosmolar therapy, just prophylactically. I don't think there's any benefit that this helps as well, and the same thing for antiepileptic drugs. So, that was one important point. The second one was blood pressure lowering, and there is emphasis now that whatever you use to lower the blood pressure, you want to make sure that the blood pressure variability is very minimal and that there is a smooth kind of control over blood pressure that has been shown to be actually important in terms of help. I'm going to make them three, not two, because I think the third one is important. Dr. Negar Asdaghi:         Okay. I'll give you one more then. Dr. Magdy Selim:             Which is the first time we include this in the guideline, and with emphasis on the role of the home caregiver for hemorrhage patients and the psychological support, the education that they need, and the training that they need to actually care for these patients and how to improve their quality of life. So, I think that's an important aspect that we didn't touch upon before, and obviously very important. Dr. Negar Asdaghi:         Very important points. Let me just review them again for our listeners. So, don't do steroids, hypertonics, and preemptive antiepileptic therapies. They don't work. The second point that you raise is reduction of blood pressure, important to keep that in mind, but paying attention to blood pressure variability. And the third one, the importance of social aspect of care of patients with intracerebral hemorrhage. That's great for us. Let me just end with one last question. Magdy, thank you so much for all of this wonderful take-home messages from the current study from i-DEF and also the guidelines. There's been a lot of excitement in the field of ischemic stroke with the success of reperfusion therapies, and yet not much for intracerebral hemorrhage. What is your hope in terms of future therapies for ICH? Dr. Magdy Selim:             So, I happen to be one of the people who is very optimistic about the future of ICH. I think it's just a matter of time. But I think we need to make some changes. We need to really treat ICH as an emergency, so time is really important. And I think right now, you see a hemorrhage patient, they just put them on the side because they think that there's nothing to do. But the way I see the future evolving, and probably the breaking point to be, is that we can diagnose ICH in the field. You immediately lower the blood pressure, reverse coagulopathy if you can, and even kind of use hemostatic agents, if the FASTEST trial shows evidence to support that, and then you take them to the hospital where there might be some role for hematoma reduction using minimally invasive therapy and some other treatments like deferoxamine, or there are a lot of other agents to target the secondary injury at the same time. So, I think it's going to be a combination of things, and they need to happen in tandem and continuously, but we need to start quickly on these patients. Dr. Negar Asdaghi:         Dr. Magdy Selim, it's been a pleasure interviewing you on the podcast. We look forward to having you back and covering more of your work. Thank you for joining us. Dr. Magdy Selim:             Thank you very much for having me. Dr. Negar Asdaghi:         And this concludes our podcast for the July 2022 issue of Stroke. Please be sure to check out this month's table of contents for a full list of publications, including a series of Focus Updates on the very topic of, you guessed it, intracerebral hemorrhage. These updates are great complements to the newly published American Heart Association guidelines for the management of patients with spontaneous intracerebral hemorrhage in May 2022. Dr. Negar Asdaghi:         And with this, we end our July podcast and draw inspiration from one particular July story, which unfolded on July 20. In 1969, on this day, Commander Neil Armstrong and lunar module pilot Buzz Aldrin landed on the moon, and Armstrong became the first person to walk on the moon. The crew of Apollo 11 changed the course of history, landing humanity on another celestial body for the first time and later safely returning everyone back to earth. Armstrong, an experienced naval aviator, a test pilot, a decorated veteran, astronaut, and university professor, passed away in 2012 from complications of coronary artery disease, reminding us that every step we take in understanding, diagnosing, and treating vascular disorders is truly part of that giant leap to save the mankind. And what better way to do this than to stay alert with Stroke Alert. Dr. Negar Asdaghi:         This program is copyright of the American Heart Association, 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, visit AHAjournals.org.

Dr. James Braun, Neurosciences Pharmacy Clinical Specialist at SSM Health St. Louis, and Dr. Kyle Hoelting, Senior Manager of Drug Information at Vizient, share their insights on the use of tenecteplase vs alteplase for treating acute ischemic stroke. They also discuss the nuances of this therapeutic area and share recent work from an expert panel led by Vizient.   Guest speakers: James Braun, PharmD, BCCCP Neurosciences Pharmacy Clinical Specialist  SSM Health   Kyle Hoelting, PharmD, BCPS Senior Manager of Drug Information  Vizient   Moderator: Gretchen Brummel, PharmD, BCPS Pharmacy Executive Director Vizient Center for Pharmacy Practice Excellence   Show Notes: [00:58-3:00] James' background and his role in the treatment of stroke patients [03:01-5:09] History of tenecteplase and alteplase for ischemic stroke [05:10-6:56] Information about trials of alteplase [06:57-8:11] Where Tenecteplase fits in discussion [08:12-9:51] Differences with tenecteplase and alteplase to clinicians [9:52-12:00] What studies say about potential, practical advantages of tenecteplase [12:01-19:55] Making the switch between agents   Links | Resources: Verified Rx: Evidenced based medicine Click here Verified Rx: Show me the data! Updates on the evidence of thrombolytic use in ischemic strokes Click here Verified Rx: Information overload: tips and tricks for staying on top of the literature, part 1 Click here Verified Rx: Information overload: tips and tricks for staying on top of the literature, part 2 Click here Identifying errors and safety considerations in patients undergoing thrombolysis in acute ischemic stroke Click here EXTEND-IA TNK Click here Australian-TNK Click here Meta-analysis NIHSS outcomes Click here NOR-TEST Click here   Subscribe Today! Apple Podcasts Amazon Podcasts Google Podcasts Spotify Stitcher Android RSS Feed

This month's guest is Dr. Kevin Abrams. He discusses his article, "Perfusion Scotoma: A Potential Core Underestimation in CT Perfusion in the Delayed Time Window in Patients with Acute Ischemic Stroke," one of the June issue's Fellows' Journal Club selections. (26:53)

On Episode 17 of the Stroke Alert Podcast, host Dr. Negar Asdaghi highlights two articles from the June 2022 issue of Stroke: “Vitamin D Enhances Hematoma Clearance and Neurologic Recovery in Intracerebral Hemorrhage” and “Acute Ischemic Stroke, Depressed Left Ventricular Ejection Fraction, and Sinus Rhythm: Prevalence and Practice Patterns.” She also interviews Dr. Bruce Campbell on his article “Role of Intravenous Thrombolytics Prior to Endovascular Thrombectomy.” Dr. Negar Asdaghi:         Let's start with some questions. 1) Is vitamin D that golden key to recovery from intracerebral hemorrhage? 2) Endovascular therapies seem to have prevailed where thrombolytics have failed. In the era of fast and furious thrombectomy, what is the role of pre-thrombectomy thrombolysis? 3) And finally, 20 years of clinical research has failed to demonstrate the superiority of anticoagulation over antiplatelet therapies for treatment of patients in sinus rhythm with low left ventricular ejection fraction, and yet, our practice patterns have not changed. Why do we remain resolute in prescribing anticoagulation despite the lack of evidence? We're back here to tackle the toughest questions with our Stroke Alert Podcast because this is the latest in Stroke. Stay with us. Dr. Negar Asdaghi:         Welcome back to another extremely motivating Stroke Alert Podcast. My name is Negar Asdaghi. I'm an Associate Professor of Neurology at the University of Miami Miller School of Medicine and your host for the monthly Stroke Alert Podcast. The June 2022 issue of Stroke contains a number of interesting articles. As part of our Advances in Stroke, we have two articles, one on the topic of cost-effectiveness of stroke care to inform health policy and the second on the current state and the future of emerging stroke therapies. As part of our Original Contributions category, we have an interesting study by Dr. [Ben] Assayag and colleagues from the Department of Neurology at Tel Aviv Sourasky Medical Center, where we learned that just over 10% of patients with TIA and stroke developed post-traumatic stress disorder, or PTSD. Higher presenting stroke severity, preexisting white matter disease, and having anxious coping styles are risk factors for development of post-stroke PTSD. Dr. Negar Asdaghi:         In another Original Contribution, by Dr. Daehoon Kim and colleagues from Yonsei University College of Medicine in Seoul, South Korea, we read with interest on the topic of whether or not we should be anticoagulating frail patients with atrial fibrillation. In this large population-based cohort, which included patients with atrial fibrillation older than 65 years of age with frailty as defined by a score of equal or greater than five on Hospital Frailty Risk Score, we learned that despite their frailty, patients with atrial fibrillation still significantly benefit from oral anticoagulation therapy. In this study, those treated with anticoagulation had lower net adverse clinical events as compared to those untreated. We also learned that direct oral anticoagulants provided lower incidence of stroke, bleeding, and mortality over Coumadin. This paper really provided practical information on treatment of frail patients with atrial fibrillation. So, I encourage you to review these papers in addition to listening to our podcast today. Later in the podcast, I have the great pleasure of interviewing Dr. Bruce Campbell from University of Melbourne in Australia on an especially timely topic, that is the role of intravenous thrombolytics prior to endovascular therapy. Dr. Campbell is a leading authority on the topic, and his interview does not disappoint. But first, with these two articles. Dr. Negar Asdaghi:         In the setting of intracerebral hemorrhage, or ICH, aside from the primary brain insult that occurs at the time of hemorrhage, secondary brain injuries continue for days and sometimes to months mostly due to the pathological response of the brain to byproducts of hematoma lysis or RBC degradation products. Today, the majority of spontaneous ICH cases are not surgically evacuated, so we rely on the body's own ability to clear blood for hematoma clearance, and obviously the faster the clearance, the better the outcome. Erythrophagocytosis by monocyte-derived macrophages contributes to hematoma clearance and ultimately to the functional recovery from ICH. So, it's conceivable that therapeutic approaches to enhance the endogenous erythrophagocytosis can potentially improve ICH outcomes. Vitamin D has been known to have variety of functions within the central nervous system, and it turns out that it may also be one such therapeutic option to improve the much needed erythrophagocytosis in intracerebral hemorrhage. Dr. Negar Asdaghi:         In the current issue of the journal, in the study titled "Vitamin D Enhances Hematoma Clearance and Neurologic Recovery in Intracerebral Hemorrhage," a group of researchers led by Dr. Jiaxin Liu from the Department of Surgery at Queen Mary Hospital at the University of Hong Kong studied the effects of oral vitamin D administered two hours after the induction of hematoma in a rodent model of ICH using direct collagenase injection into the striatum of the mouse. Eighty-nine young mice and 78 middle-aged mice were included in the study and randomly divided into three groups. Group one were sham-operated mice; group two, ICH mice treated with vehicle, which was corn oil; and group three, vitamin D-treated ICH mice. In the third group, 1000 international unit per kg of vitamin D diluted in corn oil was administered orally using a pipette two hours after the induction of ICH to mice, and then daily afterwards. And here are their top three findings of this study. Dr. Negar Asdaghi:         Number one, vitamin D-treated mice did better than vehicle on two neurobehavioral tests that were completed in the study. On the cylinder test, treatment with vitamin D significantly alleviated the asymmetric usage of four limbs at day seven, and vitamin D elongated the duration that the mice could run on the accelerated rod at day 10 on the rotarod test. Dr. Negar Asdaghi:         Number two, in terms of hematoma resolution and perihematoma edema, it's an issue that we deal with, with ICH, they used MRI imaging for edema measurement on T2-weighted images, and then sacrificed the mice and used digital quantification of hematoma volume with fresh brain specimens. And they found that treatment with vitamin D significantly alleviated both the ICH-associated brain swelling on MR and resulted in significant reduction in hematoma volume on the fresh brain specimens when compared with the vehicle-treated group at day three and day five. Dr. Negar Asdaghi:         And finally, their third main finding is in terms of erythrophagocytosis. So, the pathway that is mediated by the monocyte-derived macrophages is an endogenous pathway, that is, PPAR-γ (which stands for peroxisome proliferator-activated receptor γ) and its downstream scavenger receptor CD36 mediated. This pathway is essential for directing the endogenous erythrophagocytosis. Using flow cytometry, they found that vitamin D-treated mice had more mature macrophages expressing the scavenger receptor CD36, which was not expressed by the undifferentiated monocytes. Dr. Negar Asdaghi:         Western blot analysis confirmed that vitamin D treatment increased the tissue levels of CD36 and the upstream PPAR-γ levels in the brain at day five after collagenase model. Locally, vitamin D-enriched phagocytes that were positive for PPAR-γ and CD36 in the perihematoma regions. So, in summary, vitamin D increased the number of mature macrophages rather than undifferentiated monocytes in the perihematoma region and accelerated the differentiation of reparative macrophages from bone marrow-derived monocytes. So, bottom line is that in vitamin D, we have a simple, accessible, and well-tolerated agent to improve both the ICH outcomes and enhance hematoma resolution, but this we all observed in rodents. So, we stay tuned with interest to find out whether the same success will be seen in humans treated with vitamin D after intracerebral hemorrhage. Dr. Negar Asdaghi:         Patients with depressed left ventricular ejection fraction, or low EF, are at risk of development of ischemic stroke even if they remain in sinus rhythm. The optimal antithrombotic treatment for these patients is still unknown. Over the past two decades, we have a number of randomized trials studying the efficacy of oral anticoagulation, predominantly Coumadin, over aspirin therapy in prevention of all forms of stroke, that is ischemic and hemorrhagic, and death in patients with a low EF in sinus rhythm. Dr. Negar Asdaghi:         The meta-analysis of WASH, HELAS, WATCH, and WARCEF trials showed that treatment of low ejection fraction patients in sinus rhythm with Coumadin does reduce the subsequent risk of stroke, but it comes at the cost of a higher major bleeding risk in this population. The COMMANDER HF clinical trial published in New England Journal of Medicine in October 2018 studied whether low-dose rivaroxaban at 2.5 milligram BID was superior to placebo in patients with recent worsening of chronic heart failure, reduced ejection fraction, coronary artery disease, but no atrial fibrillation, and very similar to its prior counterparts, it did not show that rivaroxaban was associated with a lower rate of combined death, myocardial infarction, or stroke as compared to placebo. But very similar to prior studies, it also showed that rivaroxaban-treated patients had a lower risk of subsequent ischemic stroke. This poses a conundrum for stroke neurologists treating patients with this condition, especially after they present with an embolic-appearing stroke. So, the question is, how often do we encounter this situation, and what do we do in routine practice? We know that when there is equipoise, there's practice variation. Dr. Negar Asdaghi: In the current issue of the journal, in the study titled "Acute Ischemic Stroke, Depressed Left Ventricular Ejection Fraction, and Sinus Rhythm," Dr. Richa Sharma from the Department of Neurology at Yale School of Medicine and colleagues examined the prevalence of heart failure with sinus rhythm among hospitalized patients with acute ischemic stroke and the physician's practice patterns with regard to the choice of antithrombotics in this population. Dr. Negar Asdaghi:         So, let's look at their study. The study was comprised of five separate study cohorts of hospitalized acute ischemic stroke patients in the Greater Cincinnati Northern Kentucky Stroke Study for the year 2005, 2010, and 2015, and then four additional academic hospital-based cohorts in the United States during different timeframes. These were the Massachusetts General Hospital from 2002 to 2016, Rhode Island Hospital from 2016 to 2018, Yale-New Haven Hospital 2015 to 2017, and Cornell Acute Stroke Academic Registry from 2011 to 2018. All of these cohorts combined contributed to the 19,155 total number of patients in this study, which included over 14,000 patients that had documented left ventricular ejection fraction. Amongst those, 1,426 had a depressed EF and were included in this study. The investigator obviously excluded those with documented atrial fibrillation and flutter. And so the sample size for this analysis was 805 patients. And here are their main results. Dr. Negar Asdaghi:         The overall prevalence of this condition, that is low ejection fraction and sinus rhythm, among hospitalized acute ischemic stroke patients was 5%. It varied slightly between the different cohorts in this study from 4 to 6%. In terms of the antithrombotic treatment patterns, this information was available in close to 500 patients in the cohort. Overall, 59% of patients were discharged on an antiplatelet treatment alone, and 41% on anticoagulation. But these percentages significantly varied between the different institutions and was as low as 22% in one of the cohorts and as high as 45% in another cohort. Dr. Negar Asdaghi:         So, what were the factors that were associated with the use of anticoagulation at discharge? They found that the absolute percentage of left ventricular ejection fraction and the presenting NIH Stroke Scales were associated with anticoagulation use. That is, the lower the percentage of EF and the higher the presenting NIH Stroke Scale, the more likely physicians were to discharge the patients on an anticoagulation in univariate analysis, but in multivariate analysis, only the study site and presenting NIH Stroke Scale over eight were independently associated with anticoagulation use. Dr. Negar Asdaghi:         Now, interestingly, 2002 to 2018, which was their overall study period, was a time during which some of the largest and neutral randomized trials on the topic of anticoagulation versus antiplatelet were published, including the WATCH and the WARCEF trial. But the authors found no temporal variation in anticoagulation practice patterns before and after the publication of the results of these trials. So, it appears that we didn't change our minds. So, overall, we have some important takeaway messages from this study. We learned that 5% of hospitalized acute ischemic stroke patients have low left ventricular ejection fraction and remain in sinus rhythm without atrial fibrillation. Today, over 40% of patients with this condition are anticoagulated at discharge despite the results of the randomized trials, but the practice is widely variable among different institutions, and a higher presenting NIH Stroke Scale is a significant predictor of anticoagulation use at discharge in this population. Dr. Negar Asdaghi:         Almost 20 years after the approval of intravenous thrombolysis for treatment of patients with acute ischemic stroke, endovascular therapy was approved for treatment of select ischemic stroke patients with a large vessel occlusion. The two treatments are, therefore, entangled, as one was the standard of care while the second one was being tested. Therefore, all endovascularly treated patients enrolled in randomized trials would've received intravenous thrombolysis if eligible. Now, with the overwhelming success of endovascular therapy in achieving reperfusion in areas where IV thrombolysis has drastically failed, there're still critical questions regarding the added value of IV thrombolysis to endovascularly treated patients. The critical question remains as to whether eligible ischemic stroke patients who have immediate access to endovascular thrombectomy should receive prior IV thrombolysis, or should we skip the thrombolysis step altogether and just move to the angio suite as fast as possible. And there are, of course, arguments for and against each approach. Dr. Negar Asdaghi:         In this issue of the journal, in an invited topical review titled "The Role of Intravenous Thrombolytics Prior to Endovascular Thrombectomy," we learn about these arguments as the authors go through a comprehensive review of the current literature on this issue. I'm joined today by the first author of this review, Dr. Bruce Campbell, to discuss this paper. Dr. Campbell absolutely needs no introduction to our Stroke listeners. He's a professor of neurology and head of neurology and stroke at Royal Melbourne Hospital, University of Melbourne, in Australia. He's a pioneer in the field of acute stroke therapies and acute neuroimaging. He has served as the lead investigator of multiple landmark randomized trials, including EXTEND-IA and EXTEND-IA TNK, and holds multiple leadership roles. He's the clinical director of the Stroke Foundation and co-chairs the Australian Stroke Guidelines Working Party and the coordinator of the National Brain School Training Program for Neurologists in Training. And, of course, last but not least, he's my friend. So, I'm delighted to welcome him to our podcast today. Top of the morning to you, Bruce, 6:00 a.m. in Melbourne. That's quite some dedication. Thank you for being here. Dr. Bruce Campbell:       It's great to be with you. Thanks for the invitation. Dr. Negar Asdaghi:         Congrats on the paper, really exciting topic. So, let's just start with this question as part of a case. We have a patient with an M1 occlusion, a large clinical syndrome presenting two hours out from their symptom onset, and we are at a hospital where the angio suite is ready. What are some of the benefits of basically spending time in giving IV thrombolytics first rather than quickly going to the angio suite? Dr. Bruce Campbell:       I think a key element of this case is that the patient has presented directly to a hospital with immediate access to thrombectomy. Thrombolytic used in drip-and-ship transfer patients really isn't controversial, and the recent randomized trials excluded them. So, the debate's all about this context of bridging thrombolytics in patients presenting directly to a comprehensive stroke center. And you mentioned spending time giving lytics, but in fact, if you do things in parallel, that shouldn't be the case. It shouldn't delay thrombectomy if you go and give thrombolysis. Dr. Bruce Campbell:       So, the general principle is that getting the artery open faster by any means is better, and IV thrombolytic certainly has the potential to open the artery before thrombectomy in a proportion of patients, perhaps not that many, but it may also facilitate the thrombectomy. So, in the randomized trials, reperfusion after the thrombectomy was significantly better when patients had had bridging thrombolytic despite a low rate of pre-endovascular reperfusion. Other reasons for giving the lytics are the potential safety net it provides if the thrombectomy procedure is unexpectedly delayed or fails to get the artery open, and there's also this potential for lytics to dissolve distal embolic fragments and perhaps improve microvascular reperfusion. Dr. Negar Asdaghi:         So, great. So, let me summarize for our listeners what you mentioned. First off, so these are arguments in favor of giving lytics. As you mentioned, we're not really wasting time. These processes occur in parallel, so it's not like we're wasting time in giving a therapy that is potentially not as efficacious as thrombectomy is. And number two, we have improved the possibility of early reperfusion, perhaps, with the lytics. And if there are some fragments or distal clots that thrombectomy wouldn't have reached, then the lytics would. And then also there is also the chance that the thrombectomy might have failed in difficult access, and so on and so forth, and at least the patient has some chance of revascularization with the lytics. So, if these are the arguments for giving lytics, what are the arguments against giving lytics in this scenario? Dr. Bruce Campbell:       The main argument is the potential to reduce both the intracerebral and systemic hemorrhagic complications. There's also potential cost saving by skipping thrombolytics. That's probably more relevant in low-resource settings, particularly when relatives may have to pay for the thrombolytic before treatment is initiated, and that can be burdensome and also potentially delay the thrombectomy. There's a theoretical concern about thrombus fragmentation with lytics and potential migration of the clot out of reach of the thrombectomy or to new territories. But final reperfusion, as I mentioned, was, on average, better with the patient having a lytic on board in the randomized trials. Dr. Negar Asdaghi:         Perfect. And I want to highlight this issue of thrombus fragmentation because I think our readers will read more and more about this idea of, as you mentioned, fragmentation will potentially make an accessible clot for thrombectomy inaccessible. But I see that later in our questions, we're going to address that as part of the findings of randomized trials as well. So, these are some of the arguments for and against. And before we go to the randomized trials, I'd like to get an overview of what we knew as part of observational studies and non-randomized studies prior to more recent randomized trials on this topic. Dr. Bruce Campbell:       There've been a couple of nice systematic reviews and meta-analyses of the observational data, and notably in most of these studies, the direct thrombectomy patients had contraindications to lytics, and that introduces confounding factors that are difficult to adjust for. For what that's worth, the functional independence, mortality outcomes were better in the bridging patients. Hemorrhage rates weren't always higher with the lytic, and one study by Jonathan Coutinho in JAMA Neurology for the SWIFT and STAR studies showed the opposite despite them having really careful adjustment for all the confounders they could think of. And the meta-analysis by Eva Mistry in Stroke did not detect a difference in symptomatic ICH between the direct and bridging strategies. One thing that should be less affected by the patient characteristics would be the technical efficacy outcomes, and it was interesting that in the observational data, the patients who'd had bridging lytic had higher mTICI 2b-3 rates and also fewer device passes. Dr. Negar Asdaghi:         Okay. And now we do have further information with all of these new randomized trials. So, why don't we start with some of the earlier studies, the three, SKIP, DEVT, and DIRECT-MT, and start with those studies first before we move to some more recent European trials. Dr. Bruce Campbell:       SKIP was performed in Japan, and it used the lower 0.6 milligram per kilogram dose of alteplase that's standard there, and DEVT and DIRECT-MT were performed in China. All three of them showed numerically similar functional outcomes with slight trends favoring direct thrombectomy. SKIP had a smaller sample size and did not meet its non-inferiority criteria, and the other two trials did meet their specified non-inferiority margin, but it could be argued those margins were overly generous. If you think about non-inferiority trials, we generally try to set a margin for non-inferiority such as lower 95% confidence interval for the trial intervention would sacrifice up to 50% of the reference treatment effect. And it's difficult to estimate the effect of alteplase in this specific population. But if you think of the Emberson meta-analysis of alteplase, overall zero to three hours alteplase versus placebo has a 10% effect size and mRS 0-1, three to four and a half hours of 5% effect size. And we regard that as clinically important. So, half of 5%, 2.5%, is a lot tighter margin than any of the direct randomized trials employed. Dr. Negar Asdaghi:         So, Bruce, let me recap what you just mentioned. Two out of the three earlier trials seem to suggest that perhaps skipping IV therapy is the way to go rather than bridging as these two trials met the non-inferiority criteria if we believe that non-inferiority margins you mentioned. And now we have a couple of more trials, more recent trials. Can you tell us about these trials please? Dr. Bruce Campbell:       MR CLEAN-NO IV in a European population did not demonstrate non-inferiority, and the point estimate slightly favored bridging. Interestingly, in that trial, the symptomatic intracerebral hemorrhage risk, which was one of the main drivers for trying this strategy, was 5.9% in the direct and 5.3 in the bridging group. So, there's no hint of benefit from dropping the lytic on that metric. SWIFT-DIRECT was more selective in only enrolling internal carotid and M1 occlusions, which had a lower chance of early recanalization with lytic. But the protocol also specified giving the full dose of lytic. In the other trials, it seems the alteplase infusion was often stopped once the patient was in the angio suite, so the full dose may not have been delivered. And despite very low pre-endovascular recanalization in that selected group in SWIFT-DIRECT, the end of procedure reperfusion was significantly better in the bridging group, which is a consistent finding across the trials and suggests that the lytic may improve the thrombectomy outcome. Dr. Bruce Campbell:       DIRECT-SAFE, the final of those trials, was interesting in that the patients were enrolled roughly 50:50 from Australia, New Zealand, versus Asia. And in contrast to the original three randomized trials in Asian patients, DIRECT-SAFE found a significant benefit of bridging lytic in Asian patients. So, it'd be very interesting to see the results of the IRIS individual patient data meta-analysis, but we may not find a difference in Asian versus Caucasian patients despite those initial trials and despite substantial differences in the prevalence of intracranial atherosclerosis, which has often been proposed as something that would increase the risk of having bridging thrombolytic on board. Dr. Bruce Campbell:       The original study level estimate of symptomatic hemorrhage had a borderline significant 1.8% absolute reduction in the direct group. Whether those data were not all core lab adjudicated and the final analysis may show a smaller difference than that. Notably, given that trend with symptomatic intracerebral hemorrhage, mortality did not differ significantly, and, in fact, the trend favored bridging patients. So, the symptomatic hemorrhage slight trend into increase did not translate into any hint of increased mortality. Dr. Negar Asdaghi:         So, Bruce, a lot of information, and I need a recap for me. So, let me try to recap some of the things you said, and please jump in. So, so far, the newer data really basically don't show us any convincing evidence that skipping is the way to go, and direct endovascular we really don't have data in favor of going directly to the angio suite. And the jury is still out regarding an increase in the symptomatic intracerebral hemorrhage rate amongst those that actually are pre-treated with IV therapy. Is that correct? Dr. Bruce Campbell:       That's correct. So, none of the three recent trials met their non-inferiority margins. And again, we had this issue of relatively generous non-inferiority margins, and the symptomatic hemorrhage, it would make sense that there's a small difference, but it's not really been borne out in the data to be statistically significant at this stage. And again, this individual patient data meta-analysis is keenly awaited to get the most accurate estimate on that. Dr. Negar Asdaghi:         So, while we wait that, I'm going to digress a little bit and ask you a question that's not addressed in the paper that you have in this issue of the journal, and that's the CHOICE trial. So, by now, we have the results of CHOICE trial. Do you mind first give us a brief overview of what CHOICE was and how you feel that the results of CHOICE would affect this field of direct versus bridging in general? Dr. Bruce Campbell:       CHOICE is a very interesting study in that it tested giving the intra-arterial lytic at the end of a thrombectomy procedure that had achieved an mTICI 2b or better, which is what we traditionally regarded as angiographic success. The idea was to improve microvascular flow, and that may be the case. The trial was terminated early due to logistic reasons and showed a very large effect size that requires replication. The subgroup analyses are interesting in that the benefits seem to mostly accrue in patients who'd not already had intravenous lytic. Dr. Bruce Campbell:       So, perhaps giving the IV lytic before thrombectomy can still benefit patients after the thrombectomy, as well as achieving early recanalization in a proportion of patients and perhaps facilitating the thrombectomy. The other issue to address with the DIRECT trials is that with the exception of a few patients in DIRECT-SAFE, the comparator was alteplase and not tenecteplase. And we have data from EXTEND-IA TNK that tenecteplase bridging is not just non-inferior, but superior to alteplase bridging. There's an ongoing Brazilian trial of exactly that, tenecteplase versus the direct approach, which will be very interesting. Dr. Negar Asdaghi:         So, great, Bruce. I just want to repeat this segment again for our listeners. So, CHOICE is a very interesting study, looked at giving intraarterial alteplase to patients after endovascular therapy was completed and after they'd already achieved the complete and successful revascularization, and the trial was terminated early because of logistic reasons. So, we have to keep in mind, this was a smaller study, early termination, but the effect size was pretty large in favor of giving lytics. Dr. Negar Asdaghi:         So, what you mentioned is interesting, and I think that it's really worth paying attention to, that the majority of the benefits seem to have occurred from intraarterial thrombolytics in patients that have not been given intravenous lytics prior to endovascular therapy. So, in other words, you need some sort of lytics either before or after the endovascular thrombectomy to achieve that ultimate improved outcome. So, moving forward now from the randomized trials that we have on bridging versus direct thrombectomy, you have mentioned in the paper some interesting subgroups that may benefit or not benefit as much from bridging versus direct thrombectomy. Do you want to elaborate a little more about those subgroup analyses? Dr. Bruce Campbell:       The idea of precision selection or individualized treatment is being talked about a lot given there didn't seem to be much overall difference between strategies in the randomized trials, but it's important to note that the randomized trial actually disadvantages the bridging group by delaying lytic until the patient was firstly confirmed eligible for thrombectomy and then consented and randomized. Putting that aside, if we could identify a subgroup who clearly benefit from skipping lytic and, importantly, identify them without delaying lytic for those who likely benefit, that's clearly attractive. Dr. Bruce Campbell:       Currently, I'd say we have not identified that kind of subgroup, and the planned IRIS individual patient data meta-analysis will be critical for that. Patients with a large ischemic core are one potential group where there's a high risk of bleeding hypothesized. To date, there is no definitive data to indicate the risk is lower with the direct approach. Patients who need stents certainly may benefit from not having a lytic on board because they often need adjuvant antithrombotics that could increase the bleeding risk. But the question there is whether we can confidently identify those patients before the procedure, and I think that's unclear at this stage. Patients with really large clot burdens and proximal occlusions have sometimes been said not to benefit from IV lytic based on the low rates of pre-endovascular reperfusion, but the randomized trials really hinted other benefits like this potential facilitative thrombectomy. So, that hypothesis may be insecure as well. Dr. Negar Asdaghi:         And how about age? Have you come across and has there been any signal towards an impact or interaction between age and benefit from pre-endovascular thrombectomy and thrombolytics? Dr. Bruce Campbell:       It's an interesting question because age has not generally been a treatment effect modifier in previous stroke studies with thrombolytics and thrombectomy, and the individual direct thrombectomy trials that have reported subgroups haven't shown any convincing heterogeneity by age. There's certainly no indication that older patients are at risk from bridging in what I've seen so far. Dr. Negar Asdaghi:         So, this question comes up in clinical practice all the time, that a person's older, perhaps more atrophy, more vascular risk factors and white matter disease, and they're more prone, so to speak, of having a symptomatic intracerebral hemorrhage. So, what you're saying is, from the data we have, there's really no signal in favor of withholding pre-thrombectomy lytics in this population. So, it's important to know this. Bruce, what should be our final takeaway message from this study? Dr. Bruce Campbell:       I tend to agree with the recent European Stroke Organization and ESMINT guideline that for now, patients should receive lytic as early as possible and in parallel with the decision to perform thrombectomy such that neither treatment delays the other. I think if we can identify a subgroup that benefits from direct thrombectomy, and that's confirmed in the individual patient data and meta-analysis, and we can identify them without disadvantaging the majority of patients, and also that the ongoing improvements in IV lytic strategies don't render the existing trial data obsolete, then we may, in future, skip lytic for some patients, but we are not there yet. Dr. Negar Asdaghi:         So, that's amazing, Bruce. We look forward to reviewing the paper and individual data meta-analysis and interviewing you, hopefully at a better hour your time, on that. Thank you very much for joining us on the podcast today. Dr. Bruce Campbell:       Thanks again for the invitation. It's been great talking to you. Dr. Negar Asdaghi:         Thank you. Dr. Negar Asdaghi:         And this concludes our podcast for the June 2022 issue of Stroke. Please be sure to check out this month's table of contents for the full list of publications, including three very interesting images that are presented as part of a new article type, Stroke Images, and a special report in Comments and Opinions section on "Bias in Stroke Evaluation: Rethinking the Cookie Theft Picture." June is the month of Pride, and in spirit of equality, we hope to do our part to reduce all biases in stroke processes of care, diagnosis, and outcomes as we continue to stay alert with Stroke Alert. Dr. Negar Asdaghi:         This program is copyright of the American Heart Association, 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, visit AHAjournals.org.

Editor's Summary by Anne Cappola, MD, Associate Editor of JAMA, the Journal of the American Medical Association, for the March 1, 2022 issue.

Interventional Neuroradiologist Dr. Hannes Nordmeyer and Biomedical Engineer Dr. Matt Gounis discuss compositions of tough clots, approaches to stroke thrombectomy, and bailout stenting. --- CHECK OUT OUR SPONSOR CERENOVUS https://www.jnjmedicaldevices.com/en-US/companies/cerenovus --- SHOW NOTES In this episode, interventional neuroradiologist Dr. Hannes Nordmeyer, biomedical engineering professor Dr. Matt Gounis, and our host Dr. Michael Barraza discuss compositions of tough clots, approaches for stroke thrombectomy, and bailout stenting. Dr. Nordmeyer believes that interventionalists are still struggling to find the most effective method for pulling clots. He says that the use of double stent retrievers has shown high success rates, but it would be ideal to have one retriever that can work on its own. He describes his equipment setup for a standard large vessel occlusion. Dr. Nordmeyer notes clot location and behavior within the first two passes determines whether or not the operator should continue with the stent retrieval approach or change the approach. Dr. Gounis evaluates various devices by defining “success” as achievement of TICI 3 with the first pass. He comments on the current development of very large bore aspiration catheters, such as the 088 Millipede catheter and the Tenzing catheter. He also emphasizes that the success of the procedure relies largely on the composition of the embolus. Fibrin-rich clots are less likely to integrate with the stent retriever. We discuss Dr. Nordmeyer's technique, which utilizes a microcatheter and the NIMBUS device to pin and retrieve the challenging clot. We also cover bailout stenting and the benefits of recanalization when clot removal is not possible. --- RESOURCES SWIFT DIRECT Trial: https://www.swift-direct.ch/the-swift-direct-trial/ Preclinical Evaluation of Millipede 088 Intracranial Aspiration Catheter: https://pubmed.ncbi.nlm.nih.gov/32606100/ The Novel Tenzing 7 Delivery Catheter Designed to Deliver Intermediate Catheters to the Face of Embolus Without Crossing: https://jnis.bmj.com/content/13/8/722 Factors Influencing Recanalization After Mechanical Thrombectomy With First-Pass Effect for Acute Ischemic Stroke: https://www.frontiersin.org/articles/10.3389/fneur.2021.628523/full NIMBUS Geometric Clot Extractor: https://www.jnjmedicaldevices.com/en-EMEA/news-events/cerenovus-launches-nimbustm-geometric-clot-extractor-remove-tough-clots

Editor-in-chief Shawn Kennedy and senior clinical editor Christine Moffa present the highlights of the September issue of AJN, including articles such as “Acute Ischemic Stroke,” “Reimagining Injurious Falls and Safe Mobility,” “The Troubling State of Public Health,” “Supporting Frontline Staff During the COVID-19 Pandemic,” “Improving Mental Health Awareness,” and more!

Identification of patients at high risk for secondary ischemic event, after initial event or post TIA...is minimal tissue damage really that big of a deal related to secondary stroke? Drs. Galen Henderson of Brigham and Women's Hospital and Jordan Bonomo of the University of Cincinnati discuss key perspectives from a neurocritical, emergency medicine, and stroke perspective related to this important area of medicine.

Date: May 6th, 2021 Guest Skeptic: Dr. Daniel Schwerin is employed with Prisma Health-Upstate as a clinical assistant professor, emergency medicine GME director for emergency medical services and medical director for several local EMS agencies and has lectured on prehospital stroke management. Reference: Fatima et al. Mobile stroke unit versus standard medical care in the management […]

Date: April 30th, 2021 Guest Skeptic: Dr. Justin Morgenstern is an emergency physician and the creator of the excellent #FOAMed project called First10EM.com. He is also one of the SGEM Hot Off the Press Faculty. Reference: Donaldson et al. Review article: Why is there still a debate regarding the safety and efficacy of intravenous thrombolysis in the […]

Date: October 2nd, 2020 Guest Skeptic: Dr.Barbra Backus is an emergency physician at the Emergency Department of the Erasmus University Medical Center in Rotterdam, the Netherlands. She is the creator of the HEART Score and an enthusiastic researcher. Reference: Claiborne Johnston S et al. Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA. NEJM […]