Stable Rates of Low Vitamin D Status Among Children Despite Increased Testing: A Population-Based Study.

OBJECTIVE: To determine the trends in testing and incidence of vitamin D deficiency/insufficiency in Olmsted County, Minnesota over a 16-year period. STUDY DESIGN: The Rochester Epidemiology Project (REP) was used to identify Olmsted County, Minnesota residents aged <19 years who had 25-hydroxyvitamin D [25(OH)D] levels measured between January 2, 2002 and December 31, 2017. Using each patient's first 25(OH)D measurement during this period, patients were categorized into 3 groups: <20 ng/mL, 20-50 ng/mL, and >50 ng/mL. Vitamin D deficiency/insufficiency was defined as a total 25(OH)D level of <20 ng/mL. RESULTS: There was a 42-fold increase in the proportion of the county's pediatric population tested each year, starting at 3.7 per 10 000 persons in 2002 and increasing to 156.1 per 10 000 persons in 2017. The largest increase in testing occurred in children aged ≥10 years, specifically the females in this age group, in whom we observed a 90-fold increase from 2002 to 2017. During the 16-year period, the incidence of vitamin D deficiency/insufficiency (per 10 000 persons) increased from 1.7 in 2002-2003 to 19.9 in 2016-2017, but the proportion that were tested and had vitamin D deficiency/insufficiency remained stable, with rates of 21.9% (95% CI, 16.1%-29.1%) in 2006-2007 and 18.5% (95% CI, 16.0%-21.2%) in 2016-2017. CONCLUSIONS: The proportion of the county's pediatric population who underwent vitamin D testing increased from 2002 to 2017, in parallel to the increased incidence of vitamin D deficiency/insufficiency, but the proportion tested that had vitamin D deficiency/insufficiency remained stable over time.

Fewer Circulating Natural Killer Cells 28 Days After Double Cord Blood Transplantation Predicts Inferior Survival and IL-15 Response.

Natural Killer (NK) cell immune reconstitution after double umbilical cord blood transplantation (dUCBT) is rapid and thought to be involved in graft vs. leukemia (GvL) reactions. To investigate the role of NK cell recovery on clinical outcomes, the absolute number of NK cells at Day 28 after dUCBT was determined and patients with low numbers of NK cells had inferior two year disease-free survival (hazard ratio 1.96; p=0.04). A detailed developmental and functional analysis of the recovering NK cells was performed to link NK recovery and patient survival. The proportion of NK cells in each developmental stage was similar for patients with low, medium, and high Day 28 NK cell numbers. As compared to healthy controls, patients post-transplant showed reduced NK functional responses upon K562 challenge (CD107a, IFN-γ, and TNFα); however, there were no differences based on Day 28 NK cell number. Patients with low NK numbers had 30% less STAT5 phosphorylation in response to exogenous IL-15 (p=0.04) and decreased Eomes expression (p=0.025) compared to patients with high NK numbers. Decreased STAT5 phosphorylation and Eomes expression may be indicative of reduced sensitivity to IL-15 in the low NK cell group. Incubation of patient samples with IL-15 superagonist (ALT803) increased cytotoxicity and cytokine production in all patient groups. Thus, clinical interventions, including administration of IL-15 early after transplantation may increase NK cell number and function and, in turn, improve transplantation outcomes.