We investigated the inter-relationship between two downstream effectors of vascular endothelial growth factor (VEGF), the serine-threonine kinase Akt (or protein kinase B) and the transcription factor ETS1, in tubulogenesis. We show that VEGF upregulates ETS1 transcription through an Aktdependent pathway in primary endothelial cells. Activation of Akt also results in tubule formation in vitro, a process requiring ETS1 activity. In vivo, the Drosophila ETS1 is required for cell motility per se while Akt is responsible for organized cell movement. Thus, ETS1 and Akt control different aspects of cell migration that are integrated in the regulation of vascular tubule formation. KeywordsAkt; ETS1; angiogenesis; Drosophila; tubulogenesis; tracheal development Angiogenesis is the mechanism by which new blood vessels are formed from the pre-existing vascular network (Shiojima and Walsh 2002). It is widely accepted that vascular endothelial growth factor (VEGF) is the main activator of angiogenesis, inducing basement membrane degradation, endothelial cell proliferation and cell motility (Merenmies et al. 1997). Among the cellular mechanisms that underlie angiogenesis, cell motility is the least understood. Angiogenic tubulogenesis requires, a priori, migratory potential of the vascular cells. However, the cell migration events that lead to blood vessel formation needs to be both organized and directional. In other words, simple mobilization of vascular cells does not necessarily lead to tubule formation. How organized cell movement is regulated remains unresolved. Since VEGF is sufficient for inducing tube-like structures in three dimensional cell culture systems (Nehls and Drenckhahn 1995;Papapetropoulos et al. 1997), this model provides a good approximation for dissecting the complex mechanisms involved in organized cell migration. VEGF can activate many different signaling pathways, depending on cellular context and environmental cues (Veikkola et al. 2000). Among the various responses VEGF can elicit, Akt and ETS1 have emerged as two important down-stream regulators of angiogenic cell movement.Upon growth factor stimulation, phosphatidylinositol-3-kinase (PI3K) is activated which leads to recruitment of Akt to the plasma membrane where it binds phosphoinositol lipids via its pleckstrin homology domain (Chan et al. 1999). PI3K-Akt-mediated signaling has been implicated in many aspects of cellular functions, including cell survival and cell size control, which are regulated by other growth factors such as EGF and the insulin family of proteins (Brazil et al. 2002). These Akt functions are evolutionarily conserved at least in Drosophila (Scanga et al. 2000;Potter et al. 2002;Radimerski et al. 2002). Recently PI3K and by extension, Akt, have been implicated in upregulation of angiogenesis in vivo and tubule formation in vitro (Jiang et al. 2000;Morales-Ruiz et al. 2000). Although the inductive effect of PI3K on angiogenesis has been ascribed to promoting cell migration, no studies have clearly On the other hand, ...

Background: The radial artery is commonly accessed for arterial blood sampling, invasive blood pressure monitoring, and vascular access for cardiac catheterization. Iatrogenic radial artery injury is a rare complication with potentially devastating outcomes. The purpose of our study was to identify the timing of these injuries and define a treatment algorithm. Methods: A retrospective chart review of all patients with iatrogenic radial artery injuries were identified between the years 2008 and 2018. Patient demographics, mechanism of injury, interventions, and outcomes were recorded. Results: A total of 18 patients were identified with iatrogenic radial artery injury over a 10-year period. Fifty percent of these resulted from arterial line cannulation, and 50% occurred after transradial cardiac catheterization. Thirty-three percent resulted in radial artery pseudoaneurysm (RAP), and 66% had acute radial artery thrombosis (RAT). Eleven of the 18 patients underwent operative intervention. Of the 12 patients with RAT, 4 were treated with systemic anticoagulation for 3 months. All patients with RAP who were surgically treated had resolution of symptoms on follow-up evaluation. Of the patients with RAT, 2 had persistent sensorimotor deficits after treatment, and 1 patient had multiple necrotic fingers requiring amputation. Conclusion: Radial artery injuries are an uncommon but potentially devastating complication of common invasive procedures resulting in thrombosis, pseudoaneurysm, or overt hand ischemia. The treatment options vary depending on presenting symptoms.

Background: Prosthetic breast reconstruction is the most common method for treatment of patients undergoing mastectomy. Acellular dermal matrix has become more popular in implant-based breast reconstruction. Methods: The authors conducted a retrospective review of all patients undergoing prosthetic breast reconstruction between August of 2002 and December of 2013. Patients were analyzed in terms of demographics, fill volumes, number of expansions, costs, and complications. Results: A total of 284 patients underwent mastectomy surgery with 481 implant-based breast reconstructions. Four hundred eight tissue expanders had total muscle coverage, whereas 73 had AlloDerm. The rate of overall complications and major complications was significantly higher in the AlloDerm group: 20.5 percent versus 8.8 percent (p = 0.005), and 13.7 percent versus 5.1 percent (p = 0.0001), respectively. The mean initial fill volume was significantly lower in the total muscle coverage group compared to the acellular dermal matrix group (54 ± 47 versus 167 ± 139; p = 0.00003), resulting in a higher number of expansions (8.1 versus 5.8; p = 0.000051) and longer time to full expansion (60.2 days versus 43.3 days; p = 0.0002). This did not translate into a faster time to expander exchange (162.4 days versus 162.3 days; p = 0.13). Use of AlloDerm added a mean cost of $2217 for each breast. Conclusions: Implant-based breast reconstruction has evolved with the advent of acellular dermal matrices. Although the use of acellular dermal matrix allows increased initial fill volumes and fewer total expansions, there is an increased risk of complications and increased costs, especially in patients undergoing bilateral reconstruction. Total muscle coverage remains an excellent option for providing quality breast reconstruction without increased complications. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.