Interhospital Transfer Before Thrombectomy Is Associated With Delayed Treatment and Worse Outcome in the STRATIS Registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke).

BACKGROUND: Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation. METHODS: STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0-2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass. RESULTS: A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients ( CONCLUSIONS: In this large, real-world study, interhospital transfer was associated with significant treatment delays and lower chance of good outcome. Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcomes. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02239640

Advanced particulate carrier-mediated technologies for nasal drug delivery

Nasal drug delivery has been employed as an alternate and convenient route for the systemic availability of pharmaceuticals, particularly for potent therapeutics. This is owing to the large surface area, highly permeable endothelium membrane, high total blood flow, lack of first-pass metabolism, nose-to-brain targeting, and ease of access to the nasal cavity. There are several methods for delivering medicinal agents to the targeted site in a defined and sustained release pattern. Microparticles and nanoparticlesplay a crucial role in particulate drug delivery systems because of their small size and other efficient properties such as drug stabilization, controlled release, mucoadhesion, higher mucus/tissue permeability, and subsequently improved pharmacological effect oftherapeutic molecules. This review highlights and critically evaluates the most promising, state-of-the-art nasal delivery platform using microparticles and nanoparticles as drug carriers. The article briefs about benefits, limitations, hurdles, mechanism of action, physicochemical factors, different methods to improve nasal absorption, and formulation aspects of microparticle and nanoparticlebased nasal drug delivery with its applications. Finally, this review summarizes the challenges for such formulation as far as regulatory agencies are concerned, along with safety and efficacy parameters.<br/

Interventional neurology: a reborn subspecialty

Neurologists have a long history of involvement in cerebral angiography; however, the roots of neurologist involvement in therapeutic endovascular procedures have not been previously documented. As outlined in this article, it has taken the efforts of several early pioneers to lay the ground work for interventional neurology, a specialty that has become one of the fastest growing neurological subspecialties. The ground work, along with a great clinical need, has allowed the modern interventional neurologist to tackle some of the most intractable diseases, especially those affecting the cerebral vasculature. The institutionalization of interventional neurology as a subspecialty was first advocated in 1995 in an article entitled, "Interventional Neurology, a subspecialty whose time has come." The institutions created in the wake of this article have provided the framework that has allowed interventional neurology to transition from "a subspecialty whose time has come" to a subspecialty that is here to stay and thrive

Statin use is independently associated with smaller infarct volume in nonlacunar MCA territory stroke.

BACKGROUND: Studies have shown an association between HMG-CoA reductase inhibitors (statins) and improved stroke outcomes, possibly secondary to neuroprotective properties. OBJECTIVE: To assess whether patients taking statins prior to ischemic stroke have smaller infarcts on magnetic resonance imaging (MRI), adjusting for other relevant clinical factors. DESIGN: We retrospectively reviewed the Cleveland Clinic Foundation (CCF) Neurology Inpatient Database from June 2002 through June 2004. Demographics, medications, stroke subtype, diffusion-weighted imaging (DWI) infarct volume, admission NIHSS, and hours to MRI were collected. Patients with a nonlacunar middle cerebral artery (MCA) territory infarct and MRI less than 48 hours from symptom onset were included (n= 143). A multivariable linear regression model was constructed to determine independent predictors of smaller infarct volume. RESULTS: A total of 143 patients were studied, including 38 patients taking statins at the time of their stroke. In univariate analysis, patients using statins were significantly more likely to have a history of hyperlipidemia, atrial fibrillation, and coronary artery disease and to be using coumadin, antiplatelet drugs, and angiotensin-converting enzyme inhibitors. Patients on statins had a tendency toward smaller infarcts in univariate analysis (median 25.4 cm(3) vs. 15.5 cm(3), P= 0.054). In multivariable linear regression analysis statin use, patient age, and TIA within the prior 4 weeks were independently associated with smaller DWI volumes; vessel occlusion on vascular imaging, and cardioembolic stroke subtype with larger infarct size. CONCLUSIONS: Statin use prior to the onset of nonlacunar MCA infarction was associated with a smaller infarct volume independent of other factors. Further studies utilizing both clinical and radiologic outcomes will be required to confirm these findings

2-Deoxy-D-Glucose and its Derivatives for the COVID-19 Treatment: An Update

Treatment choices for the “severe acute respiratory syndrome‐related coronavirus‐2 (SARS‐CoV‐2)” are inadequate, having no clarity on efficacy and safety profiles. Currently, no established intervention has lowered the mortality rate in the “coronavirus disease 2019 (COVID‐19)” patients. Recently, 2-deoxy-D-glucose (2-DG) has evaluated as a polypharmacological agent for COVID-19 therapy owing to its influence on the glycolytic pathway, interaction with viral proteins, and anti-inflammatory action. In May 2020, the Indian drug regulatory authority approved 2-DG as an emergency adjunct therapy in mild to severe COVID-19 patients. Clinical studies of 2-DG corroborate that it aids in faster recovery of hospitalized patients and decreases supplemental oxygen. Herein, we describe the development process, synthesis, mechanism of viral eradication, and preclinical and clinical development of 2-DG and its derivatives as molecularly targeted therapeutics for COVID-19 treatment

A 5-item scale to predict stroke outcome after cortical middle cerebral artery territory infarction: validation from results of the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) Study.

BACKGROUND AND PURPOSE: Various clinical, laboratory, and radiographic parameters have been identified as predictors of outcome for ischemic stroke. The purpose of this study was to combine these parameters into a validated scale for outcome prognostication in patients with a middle cerebral artery territory infarction. METHODS: We retrospectively reviewed 129 patients over a 2-year period and considered demographic, clinical, laboratory, and radiographic parameters as potential predictors of outcome. Inclusion criteria were unilateral hemispheric infarcts within the middle cerebral artery territory \u3e15 mm in diameter. Our primary outcome measure was a favorable recovery defined as a modified Rankin Score was ≤2 at 30 days. A multivariable model was used to determine independent predictors of outcome and weighted to create a 5-item scale to predict stroke recovery. External validation of this model was done using data from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) study. RESULTS: The 5 independent predictors of outcome were as follows: age (OR, 1.09; 95% CI, 1.03 to 1.14; P=0.001), National Institutes of Health Stroke Scale score (OR, 1.17; 95% CI, 1.06 to 1.30; P=0.003), infarct volume (OR, 1.01; 95% CI, 1.00 to 1.02; P=0.03), admission white blood cell count (8.5×10(3)/mm(3); OR, 1.16; 95% CI, 1.03 to 1.27; P=0.04), and presence of hyperglycemia (OR, 4.2; 95% CI, 1.1 to 16.4; P=0.04). Combining these variables into a point scale significantly improved prediction over the individual variables accounted alone as evidenced by the area underneath the receiver operating curve (OR, 0.91; 95% CI, 0.87 to 0.96; P=0.0001). When applied to the DEFUSE study population for validation, the model achieved a sensitivity of 83% and specificity of 86%. CONCLUSIONS: With validation from a prospective study of similar patients, this model serves as a useful clinical and research tool to predict stroke recovery after cortical middle cerebral artery territory infarction