Acquired drug resistance is a major problem in the treatment of cancer. Of the more than 500,000 annual deaths from cancer in the United States, many follow the development of resistance to chemotherapy. The emergence of resistance depends in part on the genetic instability, heterogeneity and high mutational rate of tumour cells. In contrast, endothelial cells are genetically stable, homogeneous and have a low mutational rate. Therefore, antiangiogenic therapy directed against a tumour's endothelial cells should, in principle, induce little or no drug resistance. Endostatin, a potent angiogenesis inhibitor, was administered to mice bearing Lewis lung carcinoma, T241 fibrosarcoma or B16F10 melanoma. Treatment was stopped when tumours had regressed. Tumours were then allowed to re-grow and endostatin therapy was resumed. After 6, 4 or 2 treatment cycles, respectively, no tumours recurred after discontinuation of therapy. These experiments show that drug resistance does not develop in three tumour types treated with a potent angiogenesis inhibitor. An unexpected finding is that repeated cycles of antiangiogenic therapy are followed by prolonged tumour dormancy without further therapy.

Preventable or potentially preventable deaths are rare but do occur at an academic Level I trauma center. Delay in treatment and error in judgment are the leading causes of preventable and potentially preventable deaths.

Angiogenesis is the process of sprouting and configuring new blood vessels from pre-existing blood vessels, whereas the hemostatic system maintains the liquid flow of blood by regulating platelet adherence and fibrin deposition. Both systems normally appear quiescent, yet both systems remain poised for repair of injury. With vessel injury, a rapid sequence of reactions must occur to occlude the vessel wall defect and prevent hemorrhage. Activated platelets link the margins of the defect and form a provisional barrier that is quickly enmeshed with polymerized fibrin. This clot structure initially requires immobilized vascular endothelial cells to anchor the clot and prevent further bleeding. Thereafter, endothelial cells at the clot margins become mobile, dismantling and invading the cross-linked fibrin structure to rebuild a new vessel wall.Although the positive and negative regulators that control the delicate balance of platelet reactivity and fibrin deposition have been elucidated over the past four decades, analogous proteins that control endothelial cell growth and inhibition have only been discovered within the past decade. Hemostasis and angiogenesis are becoming increasingly inter-related. Proteins generated by the hemostatic system coordinate the spatial localization and temporal sequence of clot/endothelial cell stabilization followed by endothelial cell growth and repair of a damaged blood vessel. We focus here on the regulation of angiogenesis during vessel repair mediated by proteins secreted by platelets and derived as cryptic fragments from the coagulation cascade and fibrinolytic system.

Standard chemotherapeutic drugs, when modified by the frequency and dose of administration, can target angiogenesis. This approach is referred to as antiangiogenic chemotherapy, low-dose chemotherapy, or metronomic chemotherapy. This study evaluated the feasibility of 6 months of metronomic chemotherapy, its toxicity and tolerability, surrogate markers of activity, and preliminary evidence of activity in children with recurrent or progressive cancer. Twenty consecutive children were enrolled and received continuous oral thalidomide and celecoxib with alternating oral etoposide and cyclophosphamide every 21 days for a planned duration of 6 months using antiangiogenic doses of all four drugs. Surrogate markers including bFGF, VEGF, endostatin, and thrombospondin were also evaluated. Therapy was well tolerated in this heavily pretreated population. Toxicities (predominantly reversible bone marrow suppression) responded to dose modifications. Sixty percent of the patients received less than the prescribed 6 months of therapy due to toxicity (one case of deep vein thrombosis), personal choice (1 patient), or disease progression (10 patients). Forty percent of the patients completed the 6 months of therapy, resulting in prolonged or persistent disease-free status. One quarter of all patients continue to be progression free more than 123 weeks from starting therapy. Sixteen percent of patients showed a radiographic partial response. Only elevated thrombospondin-1 levels appeared to correlate with prolonged response. This oral antiangiogenic chemotherapy regimen was well tolerated in this heavily pretreated pediatric population, which showed prolonged or persistent disease-free status, supporting the continued study of antiangiogenic/metronomic chemotherapy in human clinical trials.

Higher FFP:PRBC ratio is an independent predictor of survival in massively transfused patients. Aggressive early use of FFP may improve outcome in massively transfused trauma patients.

To determine the association of the American College of Surgeons (ACS) designation with outcomes in patients, specifically those with severe traumatic brain injuries.Design: A retrospective review. Logistic regression was performed for mortality, complications, and progression of initial neurologic insult.

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BCR is an exceedingly rare injury, occurring in 1 of 2400 blunt trauma patients. In patients arriving alive to hospital, traumatic BCR is associated with a high mortality rate, however, is not uniformly fatal.