Analyzing the Effects of Demographic Differences on Patient Outcomes Following Non-pyogenic Intracranial Venous Thrombosis.

OBJECTIVE: To investigate the effect of racial and demographic differences on the short-term outcome of patients following a non-pyogenic cerebral venous thrombosis. METHODS: Data from the National Inpatient Sample were gathered from the years 2013 to 2016. Patients who had a non-pyogenic cerebral venous thrombosis were identified. Admissions of patients between different racial groups were compared. Outcome measures included inpatient mortality, length of stay (LOS), all patients refined diagnosis-related group (APR-DRG) severity and mortality risk scores, non-routine discharges, total charges, sepsis, and urinary tract infections (UTIs). RESULTS: We identified 973 patients who were admitted with a non-pyogenic cerebral venous thrombosis between 2013 and 2016. Of those, 65.7% were classified as White, 15.6% as Black, 14.1% as Hispanic, and 4.6% as Asian or Pacific Islander. Compared to White patients, Black patients were found to have a higher severity score upon admission (2.94 ± 0.818 vs 2.77 ± 0.839; p = 0.025) as well as a longer adjusted LOS (8.085 ± 5.917 vs 6.503 ± 5.552; p = 0.004) and log LOS (0.934 ± 0.507 vs 0.773 ± 0.521; p = 0.001). On initial analysis, we found that older age, elevated WBC count, income group, anemia, and an expected primary payer of Medicare/Medicaid were significantly associated with Black race and also worse outcomes. When controlling for these variables using multivariate regression, older age, lower income group, and elevated WBC count were not significantly associated with any measures of outcome. The race was no longer associated with a higher APR-DRG severity score but was still significant for adjusted LOS (p = 0.001) and adjusted log LOS (p = 0.004). Lastly, we noted that anemia and the expected primary payer of Medicare/Medicaid were both independently and significantly associated with APR-DRG severity score (p = 0.003; p = 0.010) and the adjusted log LOS (p = 0.019; p = 0.035). CONCLUSIONS: Black patients admitted with a non-pyogenic intracranial venous thrombosis have significantly longer LOS compared to White patients. Anemia and Medicare/Medicaid as the primary expected payer also seem to play a role in longer LOS, as well as the severity of the case.

IL-27 signaling activates skin cells to induce innate antiviral proteins and protects against Zika virus infection.

In the skin, antiviral proteins and other immune molecules serve as the first line of innate antiviral defense. Here, we identify and characterize the induction of cutaneous innate antiviral proteins in response to IL-27 and its functional role during cutaneous defense against Zika virus infection. Transcriptional and phenotypic profiling of epidermal keratinocytes treated with IL-27 demonstrated activation of antiviral proteins OAS1, OAS2, OASL, and MX1 in the skin of both mice and humans. IL-27-mediated antiviral protein induction was found to occur in a STAT1- and IRF3-dependent but STAT2-independent manner. Moreover, using IL27ra mice, we demonstrate a significant role for IL-27 in inhibiting Zika virus morbidity and mortality following cutaneous, but not intravenous, inoculation. Together, our results demonstrate a critical and previously unrecognized role for IL-27 in cutaneous innate antiviral immunity against Zika virus.

A Fluorescent Cell-Based System for Imaging Zika Virus Infection in Real-Time.

Zika virus (ZIKV) is a re-emerging flavivirus that is transmitted to humans through the bite of an infected mosquito or through sexual contact with an infected partner. ZIKV infection during pregnancy has been associated with numerous fetal abnormalities, including prenatal lethality and microcephaly. However, until recent outbreaks in the Americas, ZIKV has been relatively understudied, and therefore the biology and pathogenesis of ZIKV infection remain incompletely understood. Better methods to study ZIKV infection in live cells could enhance our understanding of the biology of ZIKV and the mechanisms by which ZIKV contributes to fetal abnormalities. To this end, we developed a fluorescent cell-based reporter system allowing for live imaging of ZIKV-infected cells. This system utilizes the protease activity of the ZIKV non-structural proteins 2B and 3 (NS2B-NS3) to specifically mark virus-infected cells. Here, we demonstrate the utility of this fluorescent reporter for identifying cells infected by ZIKV strains of two lineages. Further, we use this system to determine that apoptosis is induced in cells directly infected with ZIKV in a cell-autonomous manner. Ultimately, approaches that can directly track ZIKV-infected cells at the single cell-level have the potential to yield new insights into the host-pathogen interactions that regulate ZIKV infection and pathogenesis.