Targeting therapeutic gene expression to skeletal muscle following intravenous administration is an attractive strategy for treating peripheral arterial disease (PAD), except that vector access to the ischemic limb could be a limiting factor. Since AAV serotype 9 transduces skeletal muscle at high efficiency following systemic delivery, we employed AAV-9 vectors bearing luciferase or enhanced green fluorescent protein (eGFP) reporter genes to test the hypothesis that increased desialylation of cell surface glycans secondary to hindlimb ischemia (HLI) might help offset the reduction in tissue perfusion that occurs in mouse models of PAD. The utility of the creatine kinase-based (CK6) promoter for restricting gene expression to skeletal muscle was also examined by comparing it to the cytomegalovirus (CMV) promoter after systemic administration following surgically-induced HLI. Despite reduced blood flow to ischemic limbs, CK6 promoter-driven luciferase activities in ischemic gastrocnemius (GA) muscles were ~34-, ~28-, and ~150-fold higher than in fully-perfused contralateral GA, heart, and liver, respectively, 10 days after intravenous administration. Furthermore, luciferase activity from the CK6 promoter in ischemic GA muscles was ~2-fold higher than with CMV, while in the liver CK6-driven activity was ~42-fold lower than with CMV, demonstrating that the specificity of ischemic skeletal muscle transduction can be further improved with muscle-specific promoters. Studies with Evans blue dye and fluorescently-labeled lectins revealed that vascular permeability and desialylation of cell surface glycans were increased in ischemic hindlimbs. Furthermore, AAV9/CK6/Luc vector genome copy numbers were ~6-fold higher in ischemic muscle compared to non-ischemic muscle in the HLI model, whereas this trend was reversed when the same genome was packaged in the AAV-1 capsid (which binds sialylated, as opposed to desialylated glycans), further underscoring the importance of desialylation in the ischemic enhancement of transduction displayed by AAV-9. Taken together, these findings suggest two complementary mechanisms contributing to the preferential transduction of ischemic muscle by AAV-9: increased vascular permeability and desialylation. In conclusion, ischemic muscle is preferentially targeted following systemic administration of AAV-9 in a mouse model of HLI. Unmasking of the primary AAV-9 receptor as a result of ischemia may contribute importantly to this effect.

CASS reduced operating room time, likely due to improved efficiency and accuracy. Our data demonstrate that hospitals with similar cost structure as ours, performing greater than 27 cases of 3D head and neck reconstructions per year can see a financial benefit from developing an in-house CASS program.

Single-surgeon patients required fewer postoperative visits. Fewer postoperative clinic visits may have significant socioeconomic and psychological benefits to patients. Given these results, we believe that streamlining care into an integrated multidisciplinary model would be beneficial.

Overall, patients expressed high levels of satisfaction with the quality of physician communication with and without resident involvement. Resident physician involvement in surgical clinic visits was associated with lower overall patient satisfaction and decreased likelihood of recommending the practice. In addition, we observed that resident involvement was not associated with lower communication scores in most surgical specialties, including Plastic Surgery.

Background Total parotidectomy with facial nerve sacrifice creates 2 challenging reconstructive problems: restoration of facial contour and facial nerve rehabilitation. Strong evidence suggesting that vascularized nerve grafts are superior to nonvascularized nerve grafts motivated our team to develop a chimeric scapulodorsal flap combining the usual harvestable local tissues with the vascularized latissimus dorsi motor nerve (SD-LDVxN). We present our experiences developing a new program at University of California, San Diego, highlighting our first case here, and present preliminary retrospective results focusing on the functional outcomes of facial nerve reanimation. Materials and Methods The first case performed in the United States was a 57-year-old woman with stage IVA left parotid adenoid cystic carcinoma and House-Brackmann grade 6 facial palsy. She underwent total parotidectomy with facial nerve sacrifice and a free chimeric SD-LDVxN flap reconstruction. She had an unremarkable postoperative course, and 3- and 6-month follow-up functional results are reported. Preliminary functional results from our total series of 25 patients were reported. Results At her 3-month follow-up, she was a House-Brackmann 5 with a static eFACE score of 37, dynamic eFACE score of 31, and smile eFACE score of 48. At her 6-month follow-up, she was a House-Brackmann 5 with a static eFACE score of 50, dynamic eFACE score of 27, and smile eFACE score of 53. Preliminary results from our total series of 25 patients with an average of 5 years of follow-up were a House-Brackmann 2.5 and eFACE scores of 83.1 for static facial symmetry, 67.5 for dynamic facial symmetry, and 77.7 for smile score. Twenty of the 25 patients had postoperative radiotherapy. No local tumor recurrence had been reported. The average reinnervation time was 9 months and ranged from 3 to 15 months. Conclusions The SD-LDVxN flap is a highly resourceful solution to reconstruct complex parotid defects, especially those that sacrifice the facial nerve. The vascularized nerve graft allows for primary facial reanimation. Nerve recovery may be superior to what could be expected with a conventional nerve graft.