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Background: Dual antiplatelet therapy (DAPT) is commonly employed for neuroendovascular stenting due to the significant risk of thromboembolism. Clopidogrel and aspirin are most often selected as initial DAPTs; however, there is limited literature available to support guidance of DAPT in this setting. The objective of this study was to evaluate safety and efficacy in patients whose final regimen included either DAPT with aspirin and clopidogrel (DAPT-C) or DAPT with aspirin and ticagrelor (DAPT-T)., Methods: This was a multicenter, retrospective cohort of patients who underwent neuroendovascular stenting and received DAPT between July 1, 2017, and October 31, 2020. Study participants were allocated into groups based on discharge DAPT regimen. The primary outcome was incidence of stent thrombosis at 3-6 months on DAPT-C versus DAPT-T, as defined by the presence of thrombus on imaging or new onset stroke. Secondary outcomes included major and minor bleeding and death within 3-6 months after the procedure., Results: Five hundred and seventy patients were screened across 12 sites. Of those, 486 were included (DAPT-C n = 360, DAPT-T n = 126). There was no difference in the primary outcome of stent thrombosis between the DAPT-C and DAPT-T groups (8% vs. 8%, p = 0.97) and no difference in any of the secondary safety outcomes., Conclusions: Using DAPT-C or DAPT-T regimens in a broad population of neuroendovascular stenting procedures appears to have similar safety and efficacy profiles. Further prospective evaluation is warranted to streamline the practice of DAPT selection and monitoring to determine the impact on clinical outcomes., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Emergent neuroendovascular stenting presents challenges for the utilization of antiplatelet agents., Methods: This was a multicenter, retrospective cohort of patients who underwent emergent neuroendovascular stenting. The primary endpoints were thrombotic and bleeding events in relation to the timing of antiplatelet administration, route of administration, and choice of intravenous (IV) agent and the study investigated practice variability in antiplatelet utilization., Results: Five-hundred and seventy patients were screened across 12 sites. Of those, 167 were included for data analysis. For patients who presented with ischemic stroke, artery dissection and emergent internal carotid artery (ICA) stenting who received an antiplatelet agent prior to or during the procedure, 57% were given an IV antiplatelet agent; for patients who were given an antiplatelet agent after the procedure, 96% were given an oral agent. For patients who presented for aneurysm repair and received an antiplatelet agent prior to or during the procedure, 74% were given an IV agent; patients who were given an antiplatelet agent after the completion of the procedure were given an oral antiplatelet agent 90% of the time. In patients who presented with ischemic stroke, artery dissection and emergent ICA stenting who received oral antiplatelet agents post-procedure were more likely to have thrombotic events compared to those who received oral antiplatelet agents prior to or during the procedure (29% vs 9%; p   =  0.04). There were no differences in the primary outcomes observed when comparing other antiplatelet treatment strategies., Conclusion: The optimal timing of antiplatelet administration in relation to stent placement and route of administration of antiplatelet agents is unclear. Timing and route of administration of antiplatelet agents may have an effect on thrombosis in emergent neuroendovascular stenting. Significant practice variation exists in antiplatelet agent utilization in emergent neuroendovascular stenting.

Adeno-associated virus (AAV) has emerged as a leading platform for gene delivery for treating various diseases due to its excellent safety profile and efficient transduction to various target tissues. However, the large-scale production and long-term storage of viral vectors is not efficient resulting in lower yields, moderate purity, and shorter shelf-life compared to recombinant protein therapeutics. This review provides a comprehensive analysis of upstream, downstream and formulation unit operation challenges encountered during AAV vector manufacturing, and discusses how desired product quality attributes can be maintained throughout product shelf-life by understanding the degradation mechanisms and formulation strategies. The mechanisms of various physical and chemical instabilities that the viral vector may encounter during its production and shelf-life because of various stressed conditions such as thermal, shear, freeze-thaw, and light exposure are highlighted. The role of buffer, pH, excipients, and impurities on the stability of viral vectors is also discussed. As such, the aim of this review is to outline the tools and a potential roadmap for improving the quality of AAV-based drug products by stressing the need for a mechanistic understanding of the involved processes., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Little data exist regarding the practice of sodium management in acute neurologically injured patients. This study describes the practice variations, thresholds for treatment, and effectiveness of treatment in this population., Methods: This retrospective, multicenter, observational study identified 400 ICU patients, from 17 centers, admitted for ≥48 h with subarachnoid hemorrhage (SAH), traumatic brain injury (TBI), intraparenchymal hemorrhage, or intracranial tumors between January 1, 2011 and July 31, 2012. Data collection included demographics, APACHE II, Glascow Coma Score (GCS), serum sodium (Na+), fluid rate and tonicity, use of sodium-altering therapies, intensive care unit (ICU) and hospital length of stay, and modified Rankin score upon discharge. Data were collected for the first 21 days of ICU admission or ICU discharge, whichever came first. Sodium trigger for treatment defined as the Na+ value prior to treatment with response defined as an increase of ≥4 mEq/L at 24 h., Results: Sodium-altering therapy was initiated in 34 % (137/400) of patients with 23 % (32/137) having Na + >135 mEq/L at time of treatment initiation. The most common indications for treatment were declining serum Na + (68/116, 59 %) and cerebral edema with mental status changes (21/116, 18 %). Median Na + treatment trigger was 133 mEq/L (IQR 129-139) with no difference between diagnoses. Incidence and treatment of hyponatremia was more common in SAH and TBI [SAH (49/106, 46 %), TBI (39/97, 40 %), ICH (27/102, 26 %), tumor (22/95, 23 %); p = 0.001]. The most common initial treatment was hypertonic saline (85/137, 62 %), followed by oral sodium chloride tablets (42/137, 31 %) and fluid restriction (15/137, 11 %). Among treated patients, 60 % had a response at 24 h. Treated patients had lower admission GCS (12 vs. 14, p = 0.02) and higher APACHE II scores (12 vs. 10, p = 0.001). There was no statistically significant difference in outcome when comparing treated and untreated patients., Conclusion: Sodium-altering therapy is commonly employed among neurologically injured patients. Hypertonic saline infusions were used first line in more than half of treated patients with the majority having a positive response at 24 h. Further studies are needed to evaluate the impact of various treatments on patient outcomes.

Emergency neurological life support (ENLS) is an educational program designed to provide users advisory instruction regarding management for the first few hours of a neurological emergency. The content of the course is divided into 14 modules, each addressing a distinct category of neurological injury. The course is appropriate for practitioners and providers from various backgrounds who work in environments of variable medical complexity. The focus of ENLS is centered on a standardized treatment algorithm, checklists to guide early patient care, and a structured format for communication of findings and concerns to other healthcare professionals. Certification and training in ENLS is hosted by the Neurocritical Care Society. This document introduces the concept of ENLS and describes the revisions that constitute this second version.

Careful patient monitoring using a variety of techniques including clinical and laboratory evaluation, bedside physiological monitoring with continuous or non-continuous techniques and imaging is fundamental to the care of patients who require neurocritical care. How best to perform and use bedside monitoring is still being elucidated. To create a basic platform for care and a foundation for further research the Neurocritical Care Society in collaboration with the European Society of Intensive Care Medicine, the Society for Critical Care Medicine and the Latin America Brain Injury Consortium organized an international, multidisciplinary consensus conference to develop recommendations about physiologic bedside monitoring. This supplement contains a Consensus Summary Statement with recommendations and individual topic reviews as a background to the recommendations. In this article, we highlight the recommendations and provide additional conclusions as an aid to the reader and to facilitate bedside care.

A variety of technologies have been developed to assist decision-making during the management of patients with acute brain injury who require intensive care. A large body of research has been generated describing these various technologies. The Neurocritical Care Society (NCS) in collaboration with the European Society of Intensive Care Medicine (ESICM), the Society for Critical Care Medicine (SCCM), and the Latin America Brain Injury Consortium (LABIC) organized an international, multidisciplinary consensus conference to perform a systematic review of the published literature to help develop evidence-based practice recommendations on bedside physiologic monitoring. This supplement contains a Consensus Summary Statement with recommendations and individual topic reviews on physiologic processes important in the care of acute brain injury. In this article we provide the evidentiary tables for select topics including systemic hemodynamics, intracranial pressure, brain and systemic oxygenation, EEG, brain metabolism, biomarkers, processes of care and monitoring in emerging economies to provide the clinician ready access to evidence that supports recommendations about neuromonitoring.