Implementation of automatic data extraction from an enterprise database warehouse (EDW) for validating pediatric VTE decision rule: a prospective observational study in a critical care population.

Multiple clinical risk prediction tools for hospital acquired venous thromboembolism (HA-VTE) have been developed. The objectives of this study were to develop and assess the feasibility of data extraction from Electronic Medical Records (EMR) from an enterprise database warehouse (EDW) and to test the validity of a previously developed Pediatric Clot Decision Rule (PCDR). This single-center prospective observational cohort study was conducted between March 2016 and March 2017 and included eligible patients admitted to the intensive care units. Risk score was calculated using the PCDR tool. Sensitivity, specificity, positive and negative predicted value (PPV and NPV) were calculated based on a cut-point of 3. A total of 2822 children were eligible for analysis and 5.1% (95% CI 4.2-6.2) children had a PCDR score of 3. Children with PCDR score of ≥ 3 had a 3 times higher odd of developing VTE compared to those with scores < 3 (OR 3.1; 95% CI 1.93-4.80; p < 0.001). The model performance showed that at the cutoff point of ≥ 3, both the specificity and sensitivity of the PCDR in predicting VTE was 69% and NPV of 98%. We successfully demonstrated using our EDW to populate a research database using an automatic data import. A PCDR score of ≥ 3 was associated with VTE. Collaboration through large registries will be useful in informing practices and guidelines for rare disorders such as pediatric VTE.

Regulation of COX2 expression in mouse mammary tumor cells controls bone metastasis and PGE2-induction of regulatory T cell migration.

BACKGROUND: The targeting of the immune system through immunotherapies to prevent tumor tolerance and immune suppression are at the front lines of breast cancer treatment and research. Human and laboratory studies have attributed breast cancer progression and metastasis to secondary organs such as the bone, to a number of factors, including elevated levels of prostaglandin E2 (PGE2) and the enzyme responsible for its production, cyclooxygenase 2 (COX2). Due to the strong connection of COX2 with immune function, we focused on understanding how variance in COX2 expression manipulates the immune profile in a syngeneic, and immune-competent, mouse model of breast cancer. Though there have been correlative findings linking elevated levels of COX2 and Tregs in other cancer models, we sought to elucidate the mechanisms by which these immuno-suppressive cells are recruited to breast tumor and the means by which they promote tumor tolerance. METHODOLOGY/PRINCIPAL FINDINGS: To elucidate the mechanisms by which exacerbated COX2 expression potentiates metastasis we genetically manipulated non-metastatic mammary tumor cells (TM40D) to over-express COX2 (TM40D-COX2). Over-expression of COX2 in this mouse breast cancer model resulted in an increase in bone metastasis (an observation that was ablated following suppression of COX2 expression) in addition to an exacerbated Treg recruitment in the primary tumor. Interestingly, other immune-suppressive leukocytes, such as myeloid derived suppressor cells, were not altered in the primary tumor or the circulation. Elevated levels of PGE2 by tumor cells can directly recruit CD4+CD25+ cells through interactions with their EP2 and/or EP4 receptors, an effect that was blocked using anti-PGE2 antibody. Furthermore, increased Treg recruitment to the primary tumor contributed to the greater levels of apoptotic CD8+ T cells in the TM40D-COX2 tumors. CONCLUSION/SIGNIFICANCE: Due to the systemic effects of COX2 inhibitors, we propose targeting specific EP receptors as therapeutic interventions to breast cancer progression.