A Precision Medicine Agenda in Traumatic Brain Injury.

Traumatic brain injury remains a leading cause of death and disability across the globe. Substantial uncertainty in outcome prediction continues to be the rule notwithstanding the existing prediction models. Additionally, despite very promising preclinical data, randomized clinical trials (RCTs) of neuroprotective strategies in moderate and severe TBI have failed to demonstrate significant treatment effects. Better predictive models are needed, as the existing validated ones are more useful in prognosticating poor outcome and do not include biomarkers, genomics, proteonomics, metabolomics, etc. Invasive neuromonitoring long believed to be a "game changer" in the care of TBI patients have shown mixed results, and the level of evidence to support its widespread use remains insufficient. This is due in part to the extremely heterogenous nature of the disease regarding its etiology, pathology and severity. Currently, the diagnosis of traumatic brain injury (TBI) in the acute setting is centered on neurological examination and neuroimaging tools such as CT scanning and MRI, and its treatment has been largely confronted using a "one-size-fits-all" approach, that has left us with many unanswered questions. Precision medicine is an innovative approach for TBI treatment that considers individual variability in genes, environment, and lifestyle and has expanded across the medical fields. In this article, we briefly explore the field of precision medicine in TBI including biomarkers for therapeutic decision-making, multimodal neuromonitoring, and genomics.

A new aspiration device equipped with a hydro-separator for acute ischemic stroke due to challenging soft and stiff clots.

OBJECTIVE: Fragile soft clots and stiff clots remain challenging in the treatment of acute ischemic stroke. This study aims to investigate the impact of clot stiffness on the efficacy of thrombectomy devices and a new aspiration catheter with a hydro-separator. METHODS: The Neurostar aspiration catheter has a novel hydro-separator technology that macerates clots by a stream of saline inside the catheter. The Neurostar catheter and two commercially available devices, the SOFIA aspiration catheter and Solitaire stent retriever, were tested in this study. We evaluated the efficacy of each device on clots with various stiffness in a simple in vitro model. We also assessed single-pass recanalization performance in challenging situations with large erythrocyte-rich clots and fibrin-rich clots in a realistic vascular model. RESULTS: We observed an inverse association between the clot stiffness and recanalization rates. The aspiration catheter, SOFIA ingested soft clots but not moderately stiff clots. When removing soft clots with the stent retriever, fragmentation was observed, although relatively stiff clots were well-integrated and removed. The Neurostar ingested soft clots similar to the aspiration catheter, and also aspirated stiff clots by continuous suction with hydro-separator. In the experiments with challenging clots, the Neurostar led to significantly higher recanalization rates than the stent retriever and aspiration catheter. CONCLUSIONS: The stiffness of the clots affected the efficacy of endovascular thrombectomy based on the type of device. The Neurostar catheter with hydro-separator resulted in better success rates than a commercially available aspiration catheter and stent retriever in this experimental model.

In Vitro Modeling of Human Brain Arteriovenous Malformation for Endovascular Simulation and Flow Analysis.

BACKGROUND: Current in vitro models for human brain arteriovenous malformation (AVM) analyzing the efficacy of embolic materials or flow conditions are limited by a lack of realistic anatomic features of complex AVM nidus. The purpose of this study was to evaluate a newly developed in vitro AVM model for embolic material testing, preclinical training, and flow analysis. METHODS: Three-dimensional (3D) images of the AVM nidus were extracted from 3D rotational angiography from a patient. Inner vascular mold was printed using a 3D printer, coated with polydimethylsiloxanes, and then was removed by acetone, leaving a hollow AVM model. Injections of liquid embolic material and 4-dimensional (4D) flow magnetic resonance imaging (MRI) were performed using the AVM models. Additionally, computational fluid dynamics analysis was performed to examine the flow volume rate as compared with 4D flow MRI. RESULTS: The manufacture of 3D in vitro AVM models delivers a realistic representation of human nidus vasculature and complexity derived from patients. The injection of liquid embolic agents performed in the in vitro model successfully replicated real-life treatment conditions. The model simulated the plug and push technique before penetration of the liquid embolic material into the AVM nidus. The 4D flow MRI results were comparable to computational fluid dynamics analysis. CONCLUSIONS: An in vitro human brain AVM model with realistic geometric complexities of nidus was successfully created using 3D printing technology. This AVM model offers a useful tool for training of embolization techniques and analysis of hemodynamics analysis, and development of new devices and materials.

Increased Rate of Successful First Passage Recanalization During Mechanical Thrombectomy for M2 Occlusion.

BACKGROUND: Mechanical thrombectomy (MT) is the standard of care for the treatment of acute ischemic stroke (AIS) caused by anterior circulation large-vessel occlusion. However, the true safety and efficacy of MT in medium-size vessel occlusions such as the M2 segment of the middle cerebral artery have yet to be completely defined. In this study, we analyze the safety and efficacy of MT in M2 occlusions compared with M1 occlusions. METHODS: A retrospective analysis was performed of patients with AIS secondary to M1 and M2 occlusions between 2011 and 2018. The inclusion criteria were 1) AIS secondary to M1 or M2 occlusion, 2) MT performed by stentrieval technique alone, aspiration technique, or combined stentrieval-aspiration techniques. Basic patient characteristics, number of passages, first passage recanalization success (≥TICI [Thrombolysis in Cerebral Ischemia] grade 2b), total recanalization success, hemorrhagic complications (including intracerebral hemorrhage [ICH] and subarachnoid hemorrhage), and clinical outcomes were compared between both groups. RESULTS: Two hundred and sixty patients met the inclusion criteria; 171 patients had M1 occlusion versus 89 with M2 occlusion. First passage recanalization success rate was significantly higher in the M2 group (55.1% vs. 39.2%; P = 0.015). Total recanalization success rate was higher in the M2 group but did not reach significance (83% vs. 75%; P = 0.128). Subarachnoid hemorrhage rate was significantly higher in the M2 group (25% vs. 12%; P = 0.010) but there was no difference for ICH complications (14.6% vs. 16.4%; P = 0.711). CONCLUSIONS: MT for M2 occlusions has similar overall efficacy to that for M1 occlusions, but with higher first-pass successful recanalization rates. MT for M2 occlusions has a higher risk of associated subarachnoid hemorrhage.