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Background Intracranial stent placement for the treatment of cerebral aneurysms is increasingly utilized in both ruptured and unruptured scenarios. Intravenous (IV) cangrelor is a relatively new antiplatelet agent that was initially approved for coronary interventions. In addition to our institution, five other centers have published their results using IV cangrelor in neurointerventional procedures. This article combines the aneurysm treatment data from all prior studies to provide insight into the safety and efficacy of cangrelor for intracranial aneurysm treatment. Methods A prospectively maintained database was reviewed to identify all cases of IV cangrelor administration during aneurysm embolization. 20 additional patients were identified who had not been previously published. In addition, a literature search was performed to identify prior publications regarding cangrelor in neurointervention. The data from these were combined with our institutional results in a pooled-analysis. Results Overall, 85 patients who received IV cangrelor during aneurysm embolization were identified, including 46 ruptured and 39 unruptured cases. The asymptomatic and symptomatic intracranial hemorrhage rates were 4% (2/46) for ruptured cases and 2.6% (1/39) for unruptured cases. The rate of retroperitoneal hematoma and gastrointestinal bleeding was 0%. There were no incidents of intraprocedural thromboembolic complication or intraprocedural in-stent thrombosis in either cohort. One subject suffered an ischemic stroke at 24 hours secondary to in-stent thrombosis in a ruptured case. Conclusions IV cangrelor during aneurysm embolization appears to be safe, with a symptomatic intracranial hemorrhage rate of 4% in ruptured cases and 2.6% in unruptured cases. More research is needed to determine the ideal dosing regimen. [ABSTRACT FROM AUTHOR]

Purpose Current Neurocritical Care Society guidelines on the management of cerebral edema recommend hypertonic saline (HTS) over mannitol in some scenarios, but practical questions remain regarding the appropriate administration method, concentration/dose, monitoring to ensure safe use, and storage. The aim of this article is to address these practical concerns based on the evidence currently available. Summary Many different hypertonic solutions have been studied to define the optimal hyperosmolar substance to relieve acute cerebral edema in patients with conditions such as acute ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and traumatic brain injury. Mannitol and HTS are the main hyperosmolar therapies in use in contemporary neurocritical care practice. Contemporary use of HTS has followed a circuitous path in regards to the practical aspects of dosing and formulation, with evidence mainly consisting of retrospective or observational data. The effectiveness of bolus doses of HTS to lower acutely elevated intracranial pressure is well accepted. Adverse events with use of HTS are often mild and non–clinically significant if appropriate monitoring of serum sodium and chloride concentrations is performed. Available evidence shows that peripheral administration of HTS is likely safe in certain circumstances. Timely utilization of HTS is complicated by regulatory requirements for safe storage, but with appropriate safeguards HTS can be stored in patient care areas. Conclusion HTS formulations, methods of administration, infusion rate, and storage vary by institution, and no practice standards exist. Central intravenous administration may be preferred for HTS, but peripheral intravenous administration is safe provided measures are undertaken to detect and prevent phlebitis and extravasation. The safe use of HTS is possible with proper protocols, education, and institutional safeguards in place. [ABSTRACT FROM AUTHOR]

Background: Optimal antiplatelet inhibition is vital during cerebrovascular stenting procedures, yet no standardized recommendation exists for antithrombotic therapy in these scenarios. Cangrelor is an intravenous P2Y12 inhibitor with a favorable pharmacokinetic profile for use during neuroendovascular stenting. Methods: A retrospective review of all neuroendovascular patients who underwent stenting between 1 January 2019 and 22 March 2020 and were treated with cangrelor was conducted. Thirty-seven patients met inclusion criteria. Results: All patients were administered a bolus of 5 mcg/kg of cangrelor followed by a maintenance infusion. Antiplatelet effects of cangrelor were monitored using platelet reactivity units (PRU). Based on the initial PRU, seven patients' doses were adjusted with subsequent PRUs in or near the goal range of 50–150. One patient experienced an acute intraprocedural occlusion likely related to a subtherapeutic PRU which subsequently resolved with cangrelor dose adjustment and intra-arterial tirofiban administration, and one patient experienced a post-procedure stent occlusion which required a thrombectomy and intra-arterial tirofiban administration. No hemorrhagic complications occurred. Discussion: Cangrelor utilization during neuroendovascular stenting with maintenance doses of <2 mcg/kg/min with dose adjustments based on platelet function testing has not been previously described. Cangrelor presents many advantages compared to standard therapy in patients undergoing stent placement related to its pharmacokinetic profile, rapid onset of action, ease of transition to oral P2Y12 antiplatelet agents, and measurability. Conclusion: Cangrelor is a promising alternative to currently available therapies, especially in patients with a high hemorrhagic risk. [ABSTRACT FROM AUTHOR]

We recently reported a novel form of BMP2, designated nBMP2, which is translated from an alternative downstream start codon and is localized to the nucleus rather than secreted from the cell. To examine the function of nBMP2 in the nucleus, we engineered a gene-targeted mutant mouse model (nBmp2NLStm) in which nBMP2 cannot be translocated to the nucleus. Immunohistochemistry demonstrated the presence of nBMP2 staining in the myonuclei of wild type but not mutant skeletal muscle. The nBmp2NLStm mouse exhibits altered function of skeletal muscle as demonstrated by a significant increase in the time required for relaxation following a stimulated twitch contraction. Force frequency analysis showed elevated force production in mutant muscles compared to controls from 10 to 60 Hz stimulation frequency, consistent with the mutant muscle's reduced ability to relax between rapidly stimulated contractions. Muscle relaxation after contraction is mediated by the active transport of Ca2+ from the cytoplasm to the sarcoplasmic reticulum by sarco/endoplasmic reticulum Ca2+ ATPase (SERCA), and enzyme activity assays revealed that SERCA activity in skeletal muscle from nBmp2NLStm mice was reduced to approximately 80% of wild type. These results suggest that nBMP2 plays a role in the establishment or maintenance of intracellular Ca2+ transport pathways in skeletal muscle. [ABSTRACT FROM AUTHOR]