A scoping review protocol on brain PaCO2 levels at altitude.

Background: Aeromedical transfer of patients with ischemic stroke to access hyperacute stroke treatment is becoming increasingly common. Little is known about how rapid changes of altitude and atmospheric pressure can impact cerebral perfusion and ischemic burden. In patients with ischemic stroke, there is a theoretical possibility that this physiologic response of hypoxia-driven hyperventilation at higher altitude can lead to a relative drop in PaCO2.

Safety and Efficacy of Intravenous Thrombolysis by Infarct Type in Patients with No Visible Occlusion: A Secondary Analysis of the AcT Trial.

Background: About 25% of patients with acute ischemic stroke have lacunar infarct on follow-up imaging. In this secondary analysis from the AcT (Alteplase Compared With Tenecteplase) trial, we assessed if there is variation in safety or efficacy of intravenous thrombolysis by infarct type in patients with no visible occlusion. We also determined if this effect differed between tenecteplase and alteplase.

Liberal or Restrictive Transfusion Strategy in Aneurysmal Subarachnoid Hemorrhage.

Background: The effect of a liberal red-cell transfusion strategy as compared with a restrictive strategy in patients during the critical care period after an aneurysmal subarachnoid hemorrhage is unclear.

Methods: We randomly assigned critically ill adults with acute aneurysmal subarachnoid hemorrhage and anemia to a liberal strategy (mandatory transfusion at a hemoglobin level of ≤10 g per deciliter) or a restrictive strategy (optional transfusion at a hemoglobin level of ≤8 g per deciliter). The primary outcome was an unfavorable neurologic outcome, defined as a score of 4 or higher on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability) at 12 months.

Factors Influencing Nerinetide Effect on Infarct Volume in Patients Without Alteplase in the Randomized ESCAPE-NA1 Trial.

Background: In the ESCAPE-NA1 trial (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke), treatment with nerinetide was associated with a smaller infarct volume among patients who did not receive intravenous alteplase. We assessed the effect of nerinetide on the surrogate imaging outcome of final infarct volume in patients who did not receive intravenous alteplase and explored predictors of outcome and modifiers of nerinetide's effect on infarct volume.

Methods: ESCAPE-NA1 was a multicenter, randomized trial in which patients with acute stroke with a baseline Alberta Stroke Program Early CT Score >4, undergoing endovascular thrombectomy, were randomized to receive intravenous nerinetide or placebo.

Multidisciplinary Expert Guidance for the Management of Severe Bleeding on Oral Anticoagulation: An Algorithm for Practicing Clinicians.

Bleeding complications associated with oral anticoagulant (OAC) frequently lead to emergency department visits and hospitalization. Short-term all-cause mortality after severe bleeding is substantial ranging from approximately 10% for gastrointestinal bleeding (the most frequent single site) to approximately 50% for intracranial bleeding. A protocol for multidisciplinary approach to bleeding is needed to (i) ensure rapid identification of patients at risk of adverse outcomes, (ii) optimize delivery of supportive measures, (iii) treat the source of bleeding, and (iv) administer anticoagulant reversal or hemostatic therapies judiciously for patients most likely to benefit.

Consent-Related Outcomes in the Alteplase Compared to Tenecteplase Trial.

Background And Objectives: In recent years, researchers have sought to address the challenges of obtaining informed consent for participation in acute stroke trials. We studied outcomes related to the use of deferral of consent in the phase 3 Alteplase Compared to Tenecteplase (AcT) trial.

Methods: As part of our protocol, we captured methods of consent, participant withdrawals, door-to-randomization times, and door-to-needle times.

Minimally Invasive Surgery for Spontaneous Intracerebral Hemorrhage: Meta-Analysis of High-Quality Randomized Clinical Trials.

Objectives: Spontaneous intracerebral hemorrhage (ICH) poses high mortality and morbidity rates with limited evidence-based therapeutic approaches. We aimed to evaluate the current evidence for the role of minimally invasive surgery (MIS) in the management of ICH.

Methods: This systematic review and meta-analysis followed recommended guidelines and protocols.

Advance Consent for Participation in Acute Stroke Trials: A Focus Group Study with People with Lived Experience of Stroke.

Advance consent could address many of the limitations traditional consenting methods pose to participation in acute stroke trials. We conducted a series of five focus groups with people with lived experience of stroke. Using an inductive thematic approach, two themes were developed: factors in favour of, and against, advance consent.

Endovascular treatment versus medical management for basilar artery occlusion with low-to-moderate symptoms (National Institutes of Health Stroke Scale < 10).

Background: Patients with acute basilar artery occlusion (BAO) and low-to-moderate symptoms (National Institutes of Health Stroke Scale [NIHSS] < 10) are poorly represented in thrombectomy trials. Our objective is to compare thrombectomy and best medical management (BMT) in this population.

Methods: We compared data of all consecutive patients presenting with an initial NIHSS < 10 and acute symptomatic BAO included in two registries.

Exploring Transient States of PAmKate to Enable Improved Cryogenic Single-Molecule Imaging.

Super-resolved cryogenic correlative light and electron microscopy is a powerful approach which combines the single-molecule specificity and sensitivity of fluorescence imaging with the nanoscale resolution of cryogenic electron tomography. Key to this method is active control over the emissive state of fluorescent labels to ensure sufficient sparsity to localize individual emitters. Recent work has identified fluorescent proteins (FPs) that photoactivate or photoswitch efficiently at cryogenic temperatures, but long on-times due to reduced quantum yield of photobleaching remain a challenge for imaging structures with a high density of localizations.

Prothrombin complex concentrate for direct factor Xa inhibitor-associated bleeding or before urgent surgery.

Introduction: Factor Xa inhibitor (FXaI)-associated bleeding events are common and associated with substantial morbidity. Systematic evaluation of widely available, effective, and affordable FXaI bleed management strategies is needed.

Materials And Methods: We conducted a single-center retrospective cohort study of FXaI-treated patients presenting to a tertiary academic medical center from January 2018 to May 2019 who received 25-50 IU/kg 4F-PCC for either FXaI-associated major bleeding or urgent surgery.

Advance Consent for participation in Acute Stroke Trials (ACTION): protocol for a feasibility study.

Introduction: Obtaining informed consent for research from patients in medical emergencies remains a challenge, particularly in acute stroke care as treatment must be administered quickly and patients often arrive in the hospital in a state of incapacitation. Adaptations to standard consenting approaches-such as the use of surrogate consent or deferral of consent-have significant limitations. This feasibility study aims to test a new consenting approach in acute stroke care that we call advance consent.

Understanding physician preferences about combined thrombolysis and thrombectomy in patients with large vessel occlusion: An international cross-sectional survey.

Background: A recently published individual participant-level meta-analysis found that EVT alone was not non-inferior to combined intravenous thrombolysis (IVT) and EVT. Our aim was to determine factors that influence physicians' treatment choice of IVT-alone versus EVT-alone versus a combined approach.

Methods: We performed an international, structured, invite-only survey among physicians treating patients presenting with AIS.

A Multicentre Prospective Cohort Study to Identify High-Risk Transient Ischemic Attack/Minor Stroke Patients Benefitting from Echocardiography.

Background: We aimed to derive a clinical decision rule to identify patients with transient ischemic attack (TIA) or minor stroke most likely to benefit from echocardiography.

Methods: This multicentre prospective cohort study enrolled adults diagnosed with TIA/minor stroke in the emergency department who underwent echocardiograms within 90 days, from 13 Canadian academic emergency departments from October 2006 to May 2017. Our outcome was clinically significant echocardiogram findings.

Derivation of a clinical prediction score for the diagnosis of clinically significant symptomatic carotid artery disease.

Objectives: Emergent vascular imaging identifies a subset of patients requiring immediate specialized care (i.e. carotid stenosis > 50%, dissection or free-floating thrombus).

Co-localization of NCCT hypodensity and CTA spot sign predicts substantial intracerebral hematoma expansion: The Black-&-White sign.

Background: Existing radiological markers of hematoma expansion (HE) show modest predictive accuracy. We aim to investigate a novel radiological marker that co-localizes findings from non-contrast CT (NCCT) and CT angiography (CTA) to predict HE.

Methods: Consecutive acute intracerebral hemorrhage patients admitted at Foothills Medical Centre in Calgary, Canada, were included.

Development of an engineered extracellular vesicles-based vaccine platform for combined delivery of mRNA and protein to induce functional immunity.

mRNA incorporated in lipid nanoparticles (LNPs) became a new class of vaccine modality for induction of immunity against COVID-19 and ushered in a new era in vaccine development. Here, we report a novel, easy-to-execute, and cost effective engineered extracellular vesicles (EVs)-based combined mRNA and protein vaccine platform (EV vaccine) and explore its utility in proof-of-concept immunity studies in the settings of cancer and infectious disease. As a first example, we engineered EVs, natural nanoparticle carriers shed by all cells, to contain ovalbumin mRNA and protein (EV vaccine) to serve as cancer vaccine against ovalbumin-expressing melanoma tumors.

The treatment effect across ASPECTS in acute ischemic stroke: Analysis from the AcT trial.

Background: Early ischemic changes on baseline imaging are commonly evaluated for acute stroke decision-making and prognostication.

Aims: We assess the association of early ischemic changes on clinical outcomes and whether it differs between intravenous tenecteplase and Alteplase.

Methods: Data are from the phase 3, Alteplase compared to Tenecteplase (AcT) trial.

Predicting intracerebral hemorrhage after endovascular therapy for anterior circulation strokes using CT-ASPECT, CTP-ASPECT and DWI-ASPECT: Protocol for a systematic review.

Introduction: Over the last decade, there have been significant advances in treatments for anterior ischemic stroke, most notably endovascular thrombectomy (EVT). Despite the success of EVT on overall outcomes, intracerebral hemorrhage (ICH) is an important post-procedure complication, often associated with mortality and disability. Hence, predicting the risk of ICH can inform EVT decision making.

HERMES-24 Score Derivation and Validation for Simple and Robust Outcome Prediction After Large Vessel Occlusion Treatment.

Background: Clinicians need simple and highly predictive prognostic scores to assist practical decision-making. We aimed to develop a simple outcome prediction score applied 24 hours after anterior circulation acute ischemic stroke treatment with endovascular thrombectomy and validate it in patients treated both with and without endovascular thrombectomy.

Methods: Using the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) collaboration data set (n=1764), patients in the endovascular thrombectomy arm were divided randomly into a derivation cohort (n=430) and a validation cohort (n=441).

Seasonal Variations in Stroke Occurrence.

Background: Understanding seasonal variations in stroke can help stakeholders identify underlying causes in seasonal trends, and tailor resources appropriately to times of highest needs. We sought to evaluate the seasonal occurrence of stroke and its subtypes.

Methods: We conducted a retrospective cohort study using administrative data from January 1st, 2003, to December 31st, 2017, in Ontario, Canada's most populous province.