BackgroundNeuroinflammation has been implicated in the pathophysiology of post-hemorrhagic hydrocephalus (PHH) of prematurity, but no comprehensive analysis of signaling molecules has been performed using human cerebrospinal fluid (CSF).MethodsLumbar CSF levels of key cytokines (IL-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12, TNF-α, TGF-β1, IFN-γ) and chemokines (XCL-1, CCL-2, CCL-3, CCL-19, CXCL-10, CXCL-11, CXCL-12) were measured using conventional and multiplexed Enzyme-linked Immunosorbent Assays and compared between preterm infants with PHH and those with no known neurological injury. The relationships between individual biomarker levels and specific CSF cell counts were examined.ResultsTotal protein (TP) CSF levels were elevated in the PHH subjects compared to controls. CSF levels of IL-1α, IL-4, IL-6, IL-12, TNF-α, CCL-3, CCL-19, and CXCL-10 were significantly increased in PHH whereas XCL-1 was significantly decreased in PHH. When normalizing by TP, IL-1α, IL-1β, IL-10, IL-12, CCL-3, and CCL-19 levels were significantly elevated compared to controls, while XCL-1 levels remained significantly decreased. Among those with significantly different levels in both absolute and normalized levels, only absolute CCL-19 levels showed a significant correlation with CSF nucleated cells, neutrophils, and lymphocytes. IL-1β and CXCL-10 also were correlated with total cell count, nucleated cells, red blood cells, and neutrophils.ConclusionsNeuroinflammation is likely to be an important process in the pathophysiology of PHH. To our knowledge, this is the first study to investigate CSF levels of chemokines in PHH as well as the only one to show XCL-1 selectively decreased in a diseased state. Additionally, CCL-19 was the only analyte studied that showed significant differences between groups and had significant correlation with cell count analysis. The selectivity of CCL-19 and XCL-1 should be further investigated. Future studies will further delineate the role of these cytokines and chemokines in PHH.

BACKGROUND: Multiple studies have reported higher rates of glioma in areas with higher socioeconomic status (SES) but to the authors' knowledge have not stratified by other factors, including race/ethnicity or urban versus rural location. METHODS: The authors identified the average annual age-adjusted incidence rates and calculated hazard ratios for death for gliomas of various subtypes, stratified by a county-level index for SES, race/ethnicity, US region, and rural versus urban status. RESULTS: Rates of glioma were highest in counties with higher SES (rate ratio, 1.18; 95% CI, 1.15-1.22 comparing the highest with the lowest quintiles [P < .001]). Stratified by race/ethnicity, higher rates in high SES counties persisted for white non-Hispanic individuals. Stratified by rural versus urban status, differences in incidence by SES were more pronounced among urban counties. Survival was higher for residents of high SES counties after adjustment for age and extent of surgical resection (hazard ratio, 0.82; 95% CI, 0.76-0.87 comparing the highest with the lowest quintile of SES [P < .001]). Survival was higher among white Hispanic, black, and Asian/Pacific Islander individuals compared with white non-Hispanic individuals, after adjustment for age, SES, and extent of surgical resection, and when restricted to those individuals with glioblastoma who received radiation and chemotherapy. CONCLUSIONS: The incidence of glioma was higher in US counties of high compared with low SES. These differences were most pronounced among white non-Hispanic individuals and white Hispanic individuals residing in urban areas. Better survival was observed in high SES counties, even when adjusting for extent of surgical resection, and when restricted to those who received radiation and chemotherapy for glioblastoma. Differences in incidence and survival were associated with SES and race, rather than rural versus urban status. Cancer 2019;125:3390-3400.

This database is the first of its kind assembled for population-based investigations of long-term neurosurgical outcomes in preterm infants with IVH.

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