Pancreaticoduodenectomy in high-grade pancreatic and duodenal trauma.

INTRODUCTION: High-grade pancreaticoduodenal injuries are highly morbid and may require complex surgical management. Pancreaticoduodenectomy (Whipple procedure) is sometimes utilized in the management of these injuries, but guidelines on its use are lacking. This paper aims to present our 14-year experience in management of high-grade pancreaticoduodenal injuries at our busy, urban trauma center. METHODS: A retrospective review was performed on patients (ages >15 years) presenting with high-grade (AAST-OIS Grades IV and V) injuries to the pancreas or duodenum at our Southeastern Level 1 trauma center. Inclusion criteria included high-grade injury and requirement of Whipple procedure based on surgeon discretion. Patients were divided into two groups: (1) those who underwent Whipple procedures during the index operation and (2) Whipple candidates. Whipple candidates included patients who received Whipples in a staged fashion or who would have benefited from the procedure but either died or were salvaged to another procedure. Demographics, injury patterns, management, and outcomes were compared. Primary outcome was survival to discharge. RESULTS: Of 66,272 trauma patients in this study period, 666 had pancreatic or duodenal injuries, and 20 met inclusion criteria. Of these, 6 had Whipples on the index procedure and 14 were Whipple candidates (among whom 7 had staged Whipples, 6 died before completing a Whipple, and 1 was salvaged). Median (IQR) age was 28 (22.75-40) years. Patients were 85 % male, 70 % Black. GSWs comprised 95 % of injuries. All patients had at least one concomitant injury, most commonly major vascular injury (75 %), colonic injury (65 %), and hepatic injury (60 %). In-hospital mortality among Whipple patients was 15 %. CONCLUSIONS: Complex pancreaticoduodenal injuries requiring pancreaticoduodenectomy are rare but life-threatening. In such patients, hemorrhage was the leading cause of death in the first 24 h. Approximately half underwent damage control surgery with staged Whipple Procedures. However, pancreaticoduodenectomy at the initial operation is feasible in highly selective patients, depending on the extent of injury, physiologic status, and resuscitation.

Diabetic Soft Tissue Infections.

Diabetes is a systemic illness that can cause a broad range of physiologic effects. Infection rates and wound healing are both affected through multiple mechanisms. Other physiologic changes increase risk for wounds as well as complex soft tissue infections ranging from simple cellulitis to necrotizing soft tissue infections. Clinicians and surgeons need to have a low index of suspicion for severe infection in a patient presenting with diabetes, and even more so in patients with uncontrolled diabetes.

Stem cell therapy for chronic skin wounds in the era of personalized medicine: From bench to bedside.

With the significant financial burden of chronic cutaneous wounds on the healthcare system, not to the personal burden mention on those individuals afflicted, it has become increasingly essential to improve our clinical treatments. This requires the translation of the most recent benchtop approaches to clinical wound repair as our current treatment modalities have proven insufficient. The most promising potential treatment options rely on stem cell-based therapies. Stem cell proliferation and signaling play crucial roles in every phase of the wound healing process and chronic wounds are often associated with impaired stem cell function. Clinical approaches involving stem cells could thus be utilized in some cases to improve a body's inhibited healing capacity. We aim to present the laboratory research behind the mechanisms and effects of this technology as well as current clinical trials which showcase their therapeutic potential. Given the current problems and complications presented by chronic wounds, we hope to show that developing the clinical applications of stem cell therapies is the rational next step in improving wound care.

Bone Morphogenetic Protein-9-Stimulated Adipocyte-Derived Mesenchymal Progenitors Entrapped in a Thermoresponsive Nanocomposite Scaffold Facilitate Cranial Defect Repair.

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.

Thermoresponsive Citrate-Based Graphene Oxide Scaffold Enhances Bone Regeneration from BMP9-Stimulated Adipose-Derived Mesenchymal Stem Cells.

Effective bone tissue engineering is important to overcome the unmet clinical challenges as more than 1.6 million bone grafts are done annually in the United States. Successful bone tissue engineering needs minimally three critical constituents: osteoprogenitor cells, osteogenic factors, and osteoinductive/osteoconductive scaffolds. Osteogenic progenitors are derived from multipotent mesenchymal stem cells (MSCs), which can be prepared from numerous tissue sources, including adipose tissue. We previously showed that BMP9 is the most osteogenic BMP and induces robust bone formation of immortalized mouse adipose-derived MSCs entrapped in a citrate-based thermoresponsive hydrogel referred to as PPCNg. As graphene and its derivatives emerge as promising biomaterials, here we develop a novel thermosensitive and injectable hybrid material by combining graphene oxide (GO) with PPCNg (designated as GO-P) and characterize its ability to promote bone formation. We demonstrate that the thermoresponsive behavior of the hybrid material is maintained while effectively supporting MSC survival and proliferation. Furthermore, GO-P induces early bone-forming marker alkaline phosphatase (ALP) and potentiates BMP9-induced expression of osteogenic regulators and bone markers as well as angiogenic factor VEGF in MSCs. In vivo studies show BMP9-transduced MSCs entrapped in the GO-P scaffold form well-mineralized and highly vascularized trabecular bone. Thus, these results indicate that GO-P hybrid material may function as a new biocompatible, injectable scaffold with osteoinductive and osteoconductive activities for bone regeneration.

Adenovirus-Mediated Gene Delivery: Potential Applications for Gene and Cell-Based Therapies in the New Era of Personalized Medicine.

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 2,000 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 pre-clinical 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.

3-D bioprinting technologies in tissue engineering and regenerative medicine: Current and future trends.

Advances in three-dimensional (3D) printing have increased feasibility towards the synthesis of living tissues. Known as 3D bioprinting, this technology involves the precise layering of cells, biologic scaffolds, and growth factors with the goal of creating bioidentical tissue for a variety of uses. Early successes have demonstrated distinct advantages over conventional tissue engineering strategies. Not surprisingly, there are current challenges to address before 3D bioprinting becomes clinically relevant. Here we provide an overview of 3D bioprinting technology and discuss key advances, clinical applications, and current limitations. While 3D bioprinting is a relatively novel tissue engineering strategy, it holds great potential to play a key role in personalized medicine.