With rapid advances in understanding molecular pathogenesis of human diseases in the era of genome sciences and systems biology, it is anticipated that increasing numbers of therapeutic genes or targets will become available for targeted therapies. Despite numerous setbacks, efficacious gene and/or cell-based therapies still hold the great promise to revolutionize the clinical management of human diseases. It is wildly recognized that poor gene delivery is the limiting factor for most in vivo gene therapies. There has been a long-lasting interest in using viral vectors, especially adenoviral vectors, to deliver therapeutic genes for the past two decades. Among all currently available viral vectors, adenovirus is the most efficient gene delivery system in a broad range of cell and tissue types. The applications of adenoviral vectors in gene delivery have greatly increased in number and efficiency since their initial development. In fact, among over 2000 gene therapy clinical trials approved worldwide since 1989, a significant portion of the trials have utilized adenoviral vectors. This review aims to provide a comprehensive overview on the characteristics of adenoviral vectors, including adenoviral biology, approaches to engineering adenoviral vectors, and their applications in clinical and preclinical studies with an emphasis in the areas of cancer treatment, vaccination and regenerative medicine. Current challenges and future directions regarding the use of adenoviral vectors are also discussed. It is expected that the continued improvements in adenoviral vectors should provide great opportunities for cell and gene therapies to live up to its enormous potential in personalized medicine.

No abstract

No abstract

No abstract

Background: Despite an increasing incidence and associated morbidity, the optimal timing for the surgical management of periprosthetic hip fractures remains unknown. This study sought to explore whether time to surgery was associated with medical or surgical complications. Methods: A retrospective review of Medicare data from 2010 to 2014 was performed using PearlDiver. All patients with a periprosthetic hip fracture greater than 90 days from surgery and undergoing open reduction internal fixation (ORIF) or revision total hip arthroplasty (RTHA) were included. Time to surgery was measured from diagnosis and dichotomized at 48 hours. Results: Of 342 patients undergoing ORIF, 269 (79%) had surgery within 48 hours. Of 255 patients undergoing RTHA, 142 (56%) had surgery within 48 hours. For ORIF, surgery more than 48 hours after diagnosis was associated with an increased rate of 30-day deep vein thrombosis or pulmonary embolism (15% vs 7%, P ¼ .03), which remained after adjustment (odds ratio [OR]: 2.71, 95% confidence interval [CI]: 1.11-6.45). A similar association was seen for RTHA (12% vs 6%, P ¼ .09 and OR: 2.61, 95% CI 1.01-7.24). For RTHA, surgery more than 48 hours after diagnosis was associated with an increased rate of 90-day periprosthetic joint infection (12% vs 4%, P ¼ .007), which remained after adjustment (OR: 3.86, 95% CI: 1.36-12.72). A similar but not significant association was seen for ORIF (7% vs 3%, P ¼ .18 and OR: 2.65, 95% CI: 0.73-8.91). Conclusions: Among Medicare patients with a periprosthetic hip fracture, time to surgery greater than 48 hours was associated with increased medical and surgical complications.

Background:With the increasing complexity of health care, the knowledge of business in medicine is growing more valuable. Plastic surgeons in all practice settings are constantly forced to navigate endeavors that could be better faced with the leadership, management, and administrative skills honed through a formal business education. The purpose of this study was to gather data and draw conclusions related to the motivations and outcomes of plastic surgeons with a Master of Business Administration degree (MBA).Methods:An online survey was distributed to plastic surgeons in the United States who have earned an MBA. The survey was divided into 4 main sections: demographics, MBA program description, objective assessment, and subjective assessment.Results:The majority of plastic surgeons with an MBA are in practice at an academic medical center. The 2 most popular tracks of completing the degree are during medical school and after 5 years of practice. A large proportion of plastic surgeons with an MBA experienced changes in their existing career position, namely in patient care and business roles outside of clinical practice. The most important skills surgeons subjectively felt they had improved as a result of their business education were in the areas of leadership, management, and administration.Conclusions:Overall, all the plastic surgeons felt that their MBA experience met their expectations and would recommend the degree to fellow physicians. Prime motivations included adding a new dynamic to their existing career, satisfying entrepreneurial drive, and gaining credibility in business, with monetary gains being low on the list.

Due to availability and ease of harvest, adipose tissue is a favorable source of progenitor cells in regenerative medicine, but has yet to be optimized for osteogenic differentiation. The purpose of this study was to test cranial bone healing in a surgical defect model utilizing bone morphogenetic protein-9 (BMP-9) transduced immortalized murine adipocyte (iMAD) progenitor cells in a citrate-based, phase-changing, poly(polyethylene glycol citrate-co-N-isopropylacrylamide) (PPCN)-gelatin scaffold. Mesenchymal progenitor iMAD cells were transduced with adenovirus expressing either BMP-9 or green fluorescent protein control. Twelve mice underwent craniectomy to achieve a critical-sized cranial defect. The iMAD cells were mixed with the PPCN-gelatin scaffold and injected into the defects. MicroCT imaging was performed in 2-week intervals for 12 weeks to track defect healing. Histologic analysis was performed on skull sections harvested after the final imaging at 12 weeks to assess quality and maturity of newly formed bone. Both the BMP-9 group and control group had similar initial defect sizes (P = 0.21). At each time point, the BMP-9 group demonstrated smaller defect size, higher percentage defect healed, and larger percentage defect change over time. At the end of the 12-week period, the BMP-9 group demonstrated mean defect closure of 27.39%, while the control group showed only a 9.89% defect closure (P < 0.05). The BMP-9-transduced iMADs combined with a PPCN-gelatin scaffold promote in vivo osteogenesis and exhibited significantly greater osteogenesis compared to control. Adipose-derived iMADs are a promising source of mesenchymal stem cells for further studies in regenerative medicine, specifically bone engineering with the aim of potential craniofacial applications.

No abstract