The differential proteomic response to ischemic stroke in appalachian subjects treated with mechanical thrombectomy.

INTRODUCTION: The Appalachia region of North America is known to have significant health disparities, specifically, worse risk factors and outcomes for stroke. Appalachians are more likely to have comorbidities related to stroke, such as diabetes, obesity, and tobacco use, and are often less likely to have stroke interventions, such as mechanical thrombectomy (MT), for emergent large vessel occlusion (ELVO). As our Comprehensive Stroke Center directly serves stroke subjects from both Appalachian and non-Appalachian areas, inflammatory proteomic biomarkers were identified associated with stroke outcomes specific to subjects residing in Appalachia. METHODS: There were 81 subjects that met inclusion criteria for this study. These subjects underwent MT for ELVO, and carotid arterial blood samples acquired at time of intervention were sent for proteomic analysis. Samples were processed in accordance with the Blood And Clot Thrombectomy Registry And Collaboration (BACTRAC; clinicaltrials.gov; NCT03153683). Statistical analyses were utilized to examine whether relationships between protein expression and outcomes differed by Appalachian status for functional (NIH Stroke Scale; NIHSS and Modified Rankin Score; mRS), and cognitive outcomes (Montreal Cognitive Assessment; MoCA). RESULTS: No significant differences were found in demographic data or co-morbidities when comparing Appalachian to non-Appalachian subjects. However, time from stroke onset to treatment (last known normal) was significantly longer and edema volume significantly higher in patients from Appalachia. Further, when comparing Appalachian to non-Appalachian subjects, there were significant unadjusted differences in the NIHSS functional outcome. A comprehensive analysis of 184 proteins from Olink proteomic (92 Cardiometabolic and 92 Inflammation panels) showed that the association between protein expression outcomes significantly differed by Appalachian status for seven proteins for the NIHSS, two proteins for the MoCA, and three for the mRS. CONCLUSION: Our study utilizes an ELVO tissue bank and registry to investigate the intracranial/intravascular proteomic environment occurring at the time of thrombectomy. We found that patients presenting from Appalachian areas have different levels of proteomic expression at the time of MT when compared to patients presenting from non-Appalachian areas. These proteins differentially relate to stroke outcome and could be used as prognostic biomarkers, or as targets for novel therapies. The identification of a disparate proteomic response in Appalachian patients provides initial insight to the biological basis for health disparity. Nevertheless, further investigations through community-based studies are imperative to elucidate the underlying causes of this differential response.

Preoperative prescription opioid use as an independent predictor of 90-day mortality and adverse events in craniotomy and craniectomy patients.

OBJECTIVE: A growing body of literature suggests that preoperative opioid exposure is an independent predictor of poor outcomes in surgical patients. No outcomes data exist on preoperative opioid use and craniotomies/craniectomies. The objective of this study was to determine the impact of preoperative opioid use on 90-day adverse events after craniotomy or craniectomy. METHODS: A single-center retrospective cohort study of 2445 patients undergoing a craniotomy/craniectomy between January 1, 2013, and October 1, 2018, was conducted. Baseline demographics, pre- and postoperative opioid use (morphine milligram equivalents [MMEs]), and surgical metrics were recorded. Patients were categorized based on whether they took prescription opioids preoperatively, defined as within 1 month of surgery, or were opioid naive. The outcomes were mortality and adverse events 90 days after craniotomy/craniectomy. RESULTS: Overall, 26.6% of patients composed the preoperative opioid group. The median daily MME intake among this group was 34.6 (IQR 14.1-90) MMEs. Lower employment rates (p < 0.001), uninsured status (p = 0.016), and intravenous drug use (p = 0.006) were associated with preoperative opioid use. Preoperative opioid use was associated with increased venous thromboembolism (p = 0.001), acute kidney injury (p = 0.002), acute respiratory failure (p < 0.001), myocardial infarction (p = 0.002), delirium (p < 0.001), and infection (p < 0.001). Preoperative opioid use was an independent predictor of overall 90-day adverse events (OR 1.643, 95% CI 1.289-2.095; p < 0.001) and 90-day mortality (OR 1.690, 95% CI 1.254-2.277; p < 0.001). CONCLUSIONS: Preoperative opioid use was independently associated with 90-day postoperative adverse events and mortality. Opioid use increases vulnerability in craniotomy/craniectomy patients and necessitates close monitoring to improve outcomes.