Association of Soluble ST2 With Functional Outcome, Perihematomal Edema, and Immune Response After Intraparenchymal Hemorrhage.

BACKGROUND AND OBJECTIVES: Perihematomal edema (PHE) contributes to poor outcome after deep intraparenchymal hemorrhage (IPH), which is characterized by neuroinflammation and an influx of peripherally derived innate immune cells. We previously identified soluble ST2 (sST2) as a candidate for immune-mediated secondary brain injury. Leveraging prospectively collected cohorts from 2 centers, we sought to determine whether sST2 was associated with functional outcome, PHE, and the immune response following IPH. METHODS: Patients with deep IPH were enrolled within 36 hours of ictus, and blood was collected for sST2 and immune cell measurement. Hematoma volume and PHE were measured on serial CT scans. Good outcome was defined as a modified Rankin Scale score of 0-3 at 90 days. Linear mixed-effects models were used to analyze the relationship between sST2 and PHE over time. Flow cytometry was used to identify shifts in immune cell populations associated with sST2. Immunohistochemistry of human brain tissue was used to identify ST2-expressing cells in the perihematomal region. RESULTS: The 55 included patients had a median admission Glasgow Coma Scale score of 14 (interquartile range [IQR] 9-15), an intracerebral hemorrhage (ICH) score of 1 (IQR 1-2), and a hematoma volume of 8.6 mL (IQR 3.4-13.8 mL). Receiver operating curve analysis found the sST2 level to be predictive of poor outcome with an area under the curve of 0.763 (95% CI 0.632-0.894) and Youden optimum cut point of 61.8 ng/mL (p < 0.001). sST2 remained an independent predictor after adjustment for ICH score (adjusted odds ratio 2.53, 95% CI 1.03-6.19, p = 0.042). Measurement of PHE found those patients with high sST2 to have greater edema volume over time (ß = 1.07, 95% CI 0.51-1.63, p < 0.001). High sST2 was associated with a shift toward an innate peripheral immune response (monocytes and natural killer cells; 68.6% ± 5.1% vs 47.5% ± 4.0%; p = 0.003). DISCUSSION: Our findings demonstrate that elevated sST2 links the peripheral innate immune response to PHE volume and outcome after IPH. This knowledge is relevant to future studies that seek to identify patients with IPH at highest risk for immune-mediated injury or limit injury through targeted interventions.

Twenty-Year Disparity Trends in United States Stroke Death Rate by Age, Race/Ethnicity, Geography, and Socioeconomic Status.

BACKGROUND AND OBJECTIVES: In 2017, the Centers for Disease Control and Prevention (CDC) issued an alert that, after decades of consistent decline, the stroke death rate levelled off in 2013, particularly in younger individuals and without clear origin. The objective of this analysis was to understand whether social determinants of health have influenced trends in stroke mortality. METHODS: We performed a longitudinal analysis of county-level ischemic and hemorrhagic stroke death rate per 100,000 adults from 1999 to 2018 using a Bayesian spatiotemporally smoothed CDC dataset stratified by age (35-64 years [younger] and 65 years or older [older]) and then by county-level social determinants of health. We reported stroke death rate by county and the percentage change in stroke death rate during 2014-2018 compared with that during 2009-2013. RESULTS: We included data from 3,082 counties for younger individuals and 3,019 counties for older individuals. The stroke death rate began to increase for younger individuals in 2013 (p < 0.001), and the slope of the decrease in stroke death rate tapered for older individuals (p < 0.001). During the 20-year period of our study, counties with a high social deprivation index and ≥10% Black residents consistently had the highest rates of stroke death in both age groups. Comparing stroke death rate during 2014-2018 with that during 2009-2013, larger increases in younger individuals' stroke death rate were seen in counties with ≥90% (vs <90%) non-Hispanic White individuals (3.2% mean death rate change vs 1.7%, p < 0.001), rural (vs urban) populations (2.6% vs 2.0%, p = 0.019), low (vs high) proportion of medical insurance coverage (2.9% vs 1.9%, p = 0.002), and high (vs low) substance abuse and suicide mortality (2.8 vs 1.9%, p = 0.008; 3.3% vs 1.5%, p < 0.001). In contrast to the younger individuals, in older individuals, the associations with increased death rates were with more traditional social determinants of health such as the social deprivation index, urban location, unemployment rate, and proportion of Black race and Hispanic ethnicity residents. DISCUSSION: Improvements in the stroke death rate in the United States are slowing and even reversing in younger individuals and many US counties. County-level increases in stroke death rate were associated with distinct social determinants of health for younger vs older individuals. These findings may inform targeted public health strategies.