High MafB expression following burn augments monocyte commitment and inhibits DC differentiation in hemopoietic progenitors.

We have previously shown that perturbed bone marrow progenitor development promotes hyporesponsive monocytes following experimental burn sepsis. Clinical and experimental sepsis is associated with monocyte deactivation and depletion of mDCs. Decrease in circulating DCs is reported in burn patients who develop sepsis. In our 15% TBSA scald burn model, we demonstrate a significant reduction in the circulating MHC-II(+) population and mDCs (Gr1(neg)CD11b(+)CD11c(+)) with a corresponding decrease in bone marrow MHC-II(+) cells and mDCs for up to 14 days following burn. We explored the underlying mechanism(s) that regulate bone marrow development of monocytes and DCs following burn injury. We found a robust bone marrow response with a significant increase in multipotential HSCs (LSK) and bipotential GMPs following burn injury. GMPs from burn mice exhibit a significant reduction in GATA-1, which is essential for DC development, but express high levels of MafB and M-CSFRs, both associated with monocyte production. GMPs obtained from burn mice differentiated 1.7 times more into Mϕ and 1.6-fold less into DCs compared with sham. Monocytes and DCs expressed 50% less MHC-II in burn versus sham. Increased monocyte commitment in burn GMPs was a result of high MafB and M-CSFR expressions. Transient silencing of MafB (siRNA) in GMP-derived monocytes from burn mice partially restored DC differentiation deficits and increased GATA-1 expression. We provide evidence that high MafB following burn plays an inhibitory role in monocyte-derived DC differentiation by regulating M-CSFR and GATA-1 expressions.

Development of a tool to manage patient health records in support of burn injury research.

Data captured in electronic medical records (EMRs) and paper charts have enormous potential for clinical research and to improve the quality of health care; however, accessing, organizing, and analyzing these data pose significant challenges. To address these challenges, this article reports development of a web-based application that provides for local clinical data capture as well as integration of patient data directly from an institutional EMR. A web-based system was created using an existing institutional application development framework. The application consists of a local clinical data repository, processes that integrate data from an EMR, and programs that enable end-user access, manual data capture, and analysis. Data are maintained in a relational database at the patient level in a time- oriented manner and by clinical data type. The application and data repository have been used to integrate and analyze a broad range of clinical data of 637 patients with burn injury. Research findings have shown that in addition to tracking clinical outcomes, laboratory data provide the ability to risk stratify patient populations to target high-risk individuals for case management and interventions. This effort validates the utility of web-based applications to collect local clinical data and integrate clinical data directly from an institutional EMR. This approach leverages institutionally collected clinical information and provides the flexibility to incorporate disparate data and accommodate system modifications as needed. Although the current efforts have focused on a cohort of patients with burn injury, the approach and system design are extendable to other patient types.