Characterization of natural killer cells expressing markers associated with maturity and cytotoxicity in children and young adults with sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is increasingly recognized as a red blood cell disorder modulated by abnormally increased inflammation. We have previously shown that in patients with SCD not on a disease-modifying therapy (hydroxyurea or chronic transfusions), natural killer (NK) cell numbers are increased. In the current study, we further investigated the NK cell function to determine if there was evidence of increased activation and cytotoxicity. PROCEDURE: We conducted a cross-sectional study of 44 patients with HbSS/HbSß0 thalassemia at steady state (hydroxyurea = 13, chronic transfusion = 11, no disease-modifying therapy = 20) and 23 healthy controls. Using a fresh blood sample, NK immunophenotyping was performed as follows: NK cells (CD3- CD56+ lymphocytes) were evaluated for makers associated with activation (NKG2D, NKp30, NKp44, and CD69) and maturity (CD57, killer immunoglobulin-like receptors (KIR), and CD56dim). Degranulation and cytotoxicity assays were performed to evaluate NK cell function. RESULTS: Patients with SCD who were not on disease-modifying therapy had a higher number of NK cells with an immunophenotype associated with increased cytotoxicity (NKG2D+ , NKp30+ , CD56dim+ , and KIR+ NK cells) compared with healthy controls and patients on hydroxyurea. NK cells from SCD patients not on disease-modifying therapy demonstrated significantly increased cytotoxicity (measured by assaying NK cell killing of the K562 cell line) compared with healthy controls (P = 0.005). Notably, NK cell cytotoxicity against K562 cells in the hydroxyurea or chronic transfusion patients was not significantly different from that in healthy controls. CONCLUSION: SCD is associated with increased NK cell function as well as increased NK cell numbers, which appears to be normalized with disease-modifying therapy.

Understanding Disparities in the Pediatric ICU: A Scoping Review.

BACKGROUND AND OBJECTIVES: Health disparities are pervasive in pediatrics. We aimed to describe disparities among patients who are likely to be cared for in the PICU and delineate how sociodemographic data are collected and categorized. METHODS: Using MEDLINE as a data source, we identified studies which included an objective to assess sociodemographic disparities among PICU patients in the United States. We created a review rubric, which included methods of sociodemographic data collection and analysis, outcome and exposure variables assessed, and study findings. Two authors reviewed every study. We used the National Institute on Minority Health and Health Disparities Research Framework to organize outcome and exposure variables. RESULTS: The 136 studies included used variable methods of sociodemographic data collection and analysis. A total of 30 of 124 studies (24%) assessing racial disparities used self- or parent-identified race. More than half of the studies (52%) dichotomized race as white and "nonwhite" or "other" in some analyses. Socioeconomic status (SES) indicators also varied; only insurance status was used in a majority of studies (72%) evaluating SES. Consistent, although not uniform, disadvantages existed for racial minority populations and patients with indicators of lower SES. The authors of only 1 study evaluated an intervention intended to mitigate health disparities. Requiring a stated objective to evaluate disparities aimed to increase the methodologic rigor of included studies but excluded some available literature. CONCLUSIONS: Variable, flawed methodologies diminish our understanding of disparities in the PICU. Meaningfully understanding and addressing health inequity requires refining how we collect, analyze, and interpret relevant data.