Risk factors associated with venous thromboembolism in 49,028 mastectomy patients.

Venous thromboembolism (VTE) is a potentially preventable disease that carries significant morbidity and mortality. Although malignancy is associated with increased risk for VTE, it varies according to cancer type. Despite the fact that breast cancer is the most common form of cancer in women, the incidence and risk factors associated with VTE in patients undergoing mastectomy have not been well characterized. To address this we utilized the ACS-NSQIP database to identify and characterize independent risk factors for VTE in 49,028 mastectomy patients. We identified 116 cases of VTE in the 49,028 cases analyzed (0.23%). Obesity (BMI > 30, OR = 1.91, p < 0.001), inpatient status (OR = 3.75, p < 0.001), venous catheterization (OR = 2.67, p = 0.012), prolonged operative time >3 h (OR = 4.36, p < 0.001), and immediate reconstruction (OR = 3.23, p < 0.001) were found to be independent risk factors for VTE. While the incidence of VTE is rare in mastectomy patients, the heightened awareness and increased VTE prophylaxis should be considered in high risk groups.

Enhancers of GnRH transcription embedded in an upstream gene use homeodomain proteins to specify hypothalamic expression.

GnRH, the central regulator of reproductive function, is produced by only approximately 800 highly specialized hypothalamic neurons. Previous studies identified a minimal promoter [GnRH minimal promoter (GnRH-P)] (-173/+1) and a neuron-specific enhancer [GnRH-enhancer (E)1] (-1863/-1571) as regulatory regions in the rat gene that confer this stringent specificity of GnRH expression to differentiated GnRH neurons. In transgenic mice, these two elements target only GnRH neurons but fail to drive expression in the entire population, suggesting the existence of additional regulatory regions. Here, we define two novel, highly conserved, upstream enhancers in the GnRH gene termed GnRH-E2 (-3135/-2631) and GnRH-E3 (-4199/-3895) that increase neuron-specific GnRH expression through interactions with GnRH-E1 and GnRH-P. GnRH-E2 and GnRH-E3 regulate GnRH expression through similar mechanisms via Oct-1, Msx1, and Dlx2, which bind both GnRH-E2 and the GnRH-E3 critical region at -3952/-3895. Overexpression of Dlx2 increases transcription through GnRH-E2 and GnRH-E3. Remarkably, these novel elements are contained within the 3' untranslated region of the neighboring upstream gene, yet are marked endogenously by histone modification signatures consistent with those of enhancers. Thus, GnRH-E2 and GnRH-E3 are novel regulatory elements that, together with GnRH-E1 and GnRH-P, confer the specificity of GnRH expression to differentiated and mature GnRH neurons.