Roy A. Poblete

Background: The management of spontaneous intracerebral hemorrhage (ICH) has centered around controlling blood pressure in order to prevent hematoma expansion (HE). Rate-pressure product (RPP) has emerged as a hemodynamic marker that accounts for heart rate (HR) and systolic blood pressure (SBP), both of which are crucial in modifying shear stress to the vasculature. We hypothesized that RPP in the pre-hospital hyperacute phase is positively associated with initial hematoma volume and HE. Methods: We analyzed 263 patients with primary ICH from the Field Administration of Stroke Therapy-Magnesium (FAST-MAG) study with initial and interval neuroimaging. RPP was calculated as the product of HR and SBP in pre-hospital and pre-treatment phases, stratified into quintiles. HE was defined by volume expansion of >6 mL or >33% from baseline volume on repeat neuroimaging performed within 48 h of the first scan. The primary outcome was the initial hematoma volume by quintiles of hyperacute RPP. The secondary outcome was the occurrence of HE across RPP quintiles. Multivariable logistic regression was used to assess the degree to which RPP affects HE. Results: Of the 263 patients analyzed, 116 (44%) had HE. The proportion of patients with HE or the initial hematoma volume was not statistically significant across RPP quintiles overall. HE was significantly more common in female patients or patients on anticoagulation. Conclusions: Elevated RPP was not associated with increased initial hematoma volume or subsequent HE in the hyperacute period after spontaneous ICH. Future research is necessary to determine the clinical importance of RPP as a biomarker in the clinical outcome of ICH.

Penetrating brain injuries (PBI) constitute a significant subset of traumatic brain injuries, characterized by high morbidity and mortality due to their unique pathophysiological mechanisms. Despite its clinical prevalence in civilian and military settings, progress in translational research remains limited due to a lack of well-characterized pre-clinical models that accurately replicate human PBI. Existing models often fail to adequately simulate critical aspects such as ballistic dynamics, tissue cavitation, and secondary injury cascades, limiting their translational relevance and hindering therapeutic advancements. This scoping review aims to systematically evaluate existing pre-clinical models, including animal, computational, ballistic, and hybrid simulations, to assess their methodological rigor, translational applicability and reported outcome measures. Using PRISMA-ScR guidelines, we will conduct a comprehensive literature search across multiple databases, extracting data on model characteristics, injury induction techniques, histopathological findings, biomolecular markers, and functional assessments. Additionally, bibliometric analyses will provide insights into research trends and gaps in PBI modeling, particularly concerning replicating real-world injury mechanisms and long-term functional outcomes. Through this evaluation, we aim to identify optimal experimental frameworks for studying PBI pathophysiology and recovery mechanisms while informing future model development for therapeutic advancements. The findings from this review will serve as a foundation for advancing pre-clinical PBI research, guiding future model development and therapeutic innovations, and ultimately enhancing treatment strategies and patient outcomes.

Early evidence-based medical interventions to improve patient outcomes after traumatic brain injury (TBI) are lacking. In patients admitted to the ICU after TBI, optimization of nutrition is an emerging field of interest. Specialized enteral nutrition (EN) formulas that include immunonutrition containing omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been developed and are used for their proposed anti-inflammatory and proimmune properties; however, their use has not been rigorously studied in human TBI populations. A single-center, retrospective, descriptive observational study was conducted at the LAC + USC Medical Center. Patients with severe TBI (sTBI, Glasgow Coma Scale score ≤ 8) who remained in the ICU for ≥2 weeks and received EN were identified between 2017 and 2022 using the institutional trauma registry. Those who received immunonutrition formulas containing n-3 PUFAs were compared with those who received standard, polymeric EN with regard to baseline characteristics, clinical markers of inflammation and immune function, and short-term clinical outcomes. A total of 151 patients with sTBI were analyzed. Those who received immunonutrition with n-3 PUFA supplementation were more likely to be male, younger, Hispanic/Latinx, and have polytrauma needing non-central nervous system surgery. No differences in clinical markers of inflammation or infection rate were found. In multivariate regression analysis, immunonutrition was associated with reduced hospital length of stay (LOS). ICU LOS was also reduced in the subgroup of patients with polytrauma and TBI. This study identifies important differences in patient characteristics and outcomes associated with the EN formula prescribed. Study results can directly inform a prospective pragmatic study of immunonutrition with n-3 PUFA supplementation aimed to confirm the biomechanistic and clinical benefits of the intervention.

MRI is a valuable modality for the etiologic work up in patients with cryptogenic stroke and embolic stroke of undetermined source.

Traumatic brain injury (TBI) is a common diagnosis requiring acute hospitalization. Long-term, TBI is a significant source of health and socioeconomic impact in the United States and globally. The goal of clinicians who manage TBI is to prevent secondary brain injury. In this population, post-traumatic cerebral infarction (PTCI) acutely after TBI is an important but under-recognized complication that is associated with negative functional outcomes. In this comprehensive review, we describe the incidence and pathophysiology of PTCI. We then discuss the diagnostic and treatment approaches for the most common etiologies of isolated PTCI, including brain herniation syndromes, cervical artery dissection, venous thrombosis, and post-traumatic vasospasm. In addition to these mechanisms, hypercoagulability and microcirculatory failure can also exacerbate ischemia. We aim to highlight the importance of this condition and future clinical research needs with the goal of improving patient outcomes after TBI.

Background Early evidence-based medical interventions to improve patient outcomes after traumatic brain injury (TBI) are lacking. In patients admitted to the ICU after TBI, optimization of nutrition is an emerging field of interest. Specialized enteral nutrition (EN) formulas that include immunonutrition containing omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been developed and are used for their proposed anti-inflammatory and pro-immune properties; however, their use has not been rigorously studied in human TBI populations. Methods A single-center, retrospective, descriptive observational study was conducted at LAC + USC Medical Center. Patients with severe TBI (sTBI, Glasgow Coma Scale score ≤ 8) who remained in the ICU for ≥ 2 weeks and received EN were identified between 2017 and 2022 using the institutional trauma registry. Those who received immunonutrition formulas containing n-3 PUFAs were compared to those who received standard, polymeric EN in regard to baseline characteristics, clinical markers of inflammation and immune function, and short-term clinical outcomes. Results A total of 151 patients with sTBI were analyzed. Those who received immunonutrition with n-3 PUFA supplementation were more likely to be male, younger, Hispanic/Latinx, and have polytrauma needing non-central nervous system surgery. No differences in clinical markers of inflammation or infection rate were found. In multivariate regression analysis, immunonutrition was associated with reduced hospital length of stay (LOS). ICU LOS was also reduced in the subgroup of patients with polytrauma and TBI. Conclusion This study identifies important differences in patient characteristics and outcomes associated with the EN formula prescribed. Study results can directly inform a prospective pragmatic study of immunonutrition with n-3 PUFA supplementation aimed to confirm the biomechanistic and clinical benefits of the intervention.

Emerging science continues to establish the detrimental effects of malnutrition in acute neurological diseases such as traumatic brain injury, stroke, status epilepticus and anoxic brain injury. The primary pathological pathways responsible for secondary brain injury include neuroinflammation, catabolism, immune suppression and metabolic failure, and these are exacerbated by malnutrition. Given this, there is growing interest in novel nutritional interventions to promote neurological recovery after acute brain injury. In this review, we will describe how malnutrition impacts the biomolecular mechanisms of secondary brain injury in acute neurological disorders, and how nutritional status can be optimized in both pediatric and adult populations. We will further highlight emerging therapeutic approaches, including specialized diets that aim to resolve neuroinflammation, immunodeficiency and metabolic crisis, by providing pre-clinical and clinical evidence that their use promotes neurologic recovery. Using nutrition as a targeted treatment is appealing for several reasons that will be discussed. Given the high mortality and both short- and long-term morbidity associated with acute brain injuries, novel translational and clinical approaches are needed.

The lipidome has a broad range of biological and signaling functions, including serving as a structural scaffold for membranes and initiating and resolving inflammation. To investigate the biological activity of phospholipids and their bioactive metabolites, precise analytical techniques are necessary to identify specific lipids and quantify their levels. Simultaneous quantification of a set of lipids can be achieved using high sensitivity mass spectrometry (MS) techniques, whose technological advancements have significantly improved over the last decade. This has unlocked the power of metabolomics/lipidomics allowing the dynamic characterization of metabolic systems. Lipidomics is a subset of metabolomics for multianalyte identification and quantification of endogenous lipids and their metabolites. Lipidomics-based technology has the potential to drive novel biomarker discovery and therapeutic development programs; however, appropriate standards have not been established for the field. Standardization would improve lipidomic analyses and accelerate the development of innovative therapies. This review aims to summarize considerations for lipidomic study designs including instrumentation, sample stabilization, data validation, and data analysis. In addition, this review highlights how lipidomics can be applied to biomarker discovery and drug mechanism dissection in various inflammatory diseases including cardiovascular disease, neurodegeneration, lung disease, and autoimmune disease.

Despite the high mortality and disability associated with traumatic brain injury (TBI), effective pharmacologic treatments are lacking. Of emerging interest, bioactive lipids, including specialized pro resolving lipid mediators of inflammation (SPMs), act to attenuate inflammation after injury resolution. The SPM lipidome may serve as a biomarker of disease and predictor of clinical outcomes, and the use of exogenous SPM administration represents a novel therapeutic strategy for TBI. This review article provides a comprehensive discussion of the current pre-clinical and clinical literature supporting the importance of bioactive lipids, including SPMs, in TBI recovery. We additionally propose a translational approach to answer important clinical and scientific questions to advance the study of bioactive lipids and SPMs towards clinical research. Given the morbidity and mortality associated with TBI with limited treatment options, novel approaches are needed.