Open lower extremity fractures in the geriatric population.

INTRODUCTION: Open fractures in the elderly are distinct compared to younger populations. The purpose of this study is to follow a series of open fractures of the lower extremity in the geriatric population to better prognosticate outcomes. METHODS: We performed a retrospective chart review of patients over the age of 65 years old who were treated for an open, lower extremity fracture across two level I trauma medical systems. Patients were included if they had documented wound healing problems in the postoperative period, or 6 months of follow-up, or if they had a definitive radiographic outcome. Sixty-four patients were included of an average age of 76.23, of whom 73.4% were female. RESULTS: The fracture types were midshaft femur in 3, distal femur in 9, patella in 2, proximal tibia in 3, proximal fibula in 1, midshaft tibia in 14, distil tibia in 8, ankle in 23, and talar neck/calcaneus in 1. Forty-two fractures were the result of low energy mechanism and 22 fractures were from high energy mechanism. Fourteen fractures were type 1, 32 were type 2, 11 were type 3A, 6 were type 3B, and 1 was type 3C. At final follow-up, 13 wounds were well healed, 39 wounds were healed following a delay of more than 6 weeks to achieve healing, 3 were infected, 3 had been treated with amputation, 2 had chronic ulceration, 2 with active draining, and 2 had draining sinuses. DISCUSSION: Open lower extremity fractures are serious injuries with high rates of morbidity. Such risks are even higher in the geriatric population, particularly with regard to wound healing. This study provides important prognostic information in counseling geriatric patient with an open lower extremity fracture, as well as informs treatment in terms of wound surveillance and care in the postoperative period.

Potential Benefits of Limited Clinical and Radiographic Follow-up After Surgical Treatment of Ankle Fractures.

INTRODUCTION: Ankle fractures are one of the most prevalent musculoskeletal injuries, with a significant number requiring surgical treatment. Postoperative complications requiring additional interventions frequently occur during the early postoperative period. We hypothesize that there is a limited need for routine clinical and radiographic follow-up once the fracture is deemed healed. METHODS: IRB approval was obtained at four academic trauma centers. A retrospective chart review was done to identify adults with healed unimalleolar and bimalleolar ankle fractures treated surgically with at least 12 months of follow-up. Based on postoperative radiographs, changes in fracture alignment and implant position from radiographic union to final follow-up were documented. The average reimbursement for a final follow-up clinic visit and a set of ankle radiographs were estimated. RESULTS: A total of 140 patients met inclusion criteria. The mean age at injury was 49.5 years, and 67.9% of patients were female. The mean time to healing was 82.2 days (±33.5 days). After radiographic healing, one patient had radiographic changes but was asymptomatic and full weight bearing at their final follow-up. On average, our institution was reimbursed $46 to $49 for a follow-up clinic visit and $364 to $497 for a set of ankle radiographs. CONCLUSION: Given the average time to healing, there is limited utility in routine radiographic and clinical follow-up beyond 16 weeks in asymptomatic patients. In our series, this would result in a savings of $950 to $1,200 per patient. However, after ankle fractures were deemed healed, 0.7% patients had radiographic evidence of a change in implant position. Documenting this change did not modify the immediate course of fracture treatment. Surgeons will need to balance the need for routine follow-up with the potential economic benefits in reducing costs to the healthcare system.

Preclinical evaluation of a novel implant for treatment of a full-thickness distal femoral focal cartilage defect.

A novel, nonresorbable, monolithic composite structure ceramic, developed using a partially stabilized zirconia ceramic common to implantable devices, was used in a cementless weight-bearing articular implant to test the feasibility of replacing a region of degenerated or damaged articular cartilage in the knee as part of a preclinical study using male mongrel dogs lasting up to 24 weeks. Gross/histological cartilage observations showed no differences among control, 12-week and 24-week groups, while pull-out tests showed an increase in maximum pull-out load over time relative to controls. Hence, the use of a novel ceramic implant as a replacement for a focal cartilage defect leads to effective implant fixation within 12 weeks and does not cause significant degradation in opposing articular cartilage in the time frame evaluated.

Rodent models for the study of articular fracture healing.

The goal of this study was to document the healing time course and expression of ex vivo cell-based gene delivery in articular fracture models in the mouse and rat. Articular medial intercondylar femoral osteotomy was performed in the stifle (knee) joints of hairless immunocompetent mice and medial or lateral similar osteotomy was performed in athymic nude rats. Genetically modified cells expressing luciferase were delivered in a three-dimensional alginate matrix directly into the osteotomy site. Sensitivity of an in vivo imaging system to detect expression of luciferase was compared between rodents in this fracture model. Osteotomy healing was assessed using high-detail radiography, helical computed tomography (CT), high-field magnetic resonance imaging, and histology. The mouse model was less satisfactory because the small size of the murine femur made reliable assessment of fracture healing restricted to histopathology, and complications occurred in 11/24 mice (45.8%), most frequently transverse supracondylar femoral fracture postoperatively. Gene expression was inconsistently confirmed in mice in vivo for 11 days (p < .003). In rats, high-detail radiography and CT were used to assess osteotomy healing. Magnetic resonance imaging (4.7 T) in rats could produce three-dimensional images that would permit assessment of bone and cartilage, but was time-consuming and expensive. In rats, the only surgical complication, transverse femoral fracture, was reduced from 83.3% with the medial osteotomy to 0% with a lateral osteotomy. In vivo imaging confirmed gene expression in the alginate/cell constructs in rats for at least 4 days (p < .05). The nude rat model has the advantage of larger femora and the ability to implant xenograft cells. A lateral intercondylar osteotomy of the distal femur in the rat can be used to study the healing of articular fractures.

Evaluation of permissiveness and cytotoxic effects in equine chondrocytes, synovial cells, and stem cells in response to infection with adenovirus 5 vectors for gene delivery.

OBJECTIVE: To evaluate host cell permissiveness and cytotoxic effects of recombinant and modified adenoviral vectors in equine chondrocytes, synovial cells, and bone marrow-derived mesenchymal stem cells (BMD-MSCs). SAMPLE POPULATION: Articular cartilage, synovium, and bone marrow from 15 adult horses. PROCEDURES: Equine chondrocytes, synovial cells, and BMD-MSCs and human carcinoma (HeLa) cells were cultured and infected with an E-1-deficient adenovirus vector encoding the beta-galactosidase gene or the green fluorescent protein gene (Ad-GFP) and with a modified E-1-deficient vector with the arg-gly-asp capsid peptide insertion and containing the GFP gene (Ad-RGD-GFP). Percentages of transduced cells, total and transduced cell counts, and cell viability were assessed 2 and 7 days after infection. RESULTS: -Permissiveness to adenoviral vector infection was significantly different among cell types and was ranked in decreasing order as follows: HeLa cells > BMD-MSCs > chondrocytes > synovial cells. Morphologic signs of cytotoxicity were evident in HeLa cells but not in equine cells. Numbers of transduced cells decreased by day 7 in all cell types except equine BMD-MSCs. Transduction efficiency was not significantly different between the Ad-GFP and Ad-RGD-GFP vectors. CONCLUSION AND CLINICAL RELEVANCE: Sufficient gene transfer may be achieved by use of an adenovirus vector in equine cells. High vector doses can be used in equine cells because of relative resistance to cytotoxic effects in those cells. Greater permissiveness and sustained expression of transgenes in BMD-MSCs make them a preferential cell target for gene therapy in horses.

Gene-mediated osteogenic differentiation of stem cells by bone morphogenetic proteins-2 or -6.

Bone marrow-derived mesenchymal stem cells (BMDMSC) hold promise for targeted osteogenic differentiation and can be augmented by delivery of genes encoding bone morphogenetic proteins (BMP). The feasibility of promoting osteogenic differentiation of BMDMSC was investigated using two BMP genes in monolayer and three-dimensional alginate culture systems. Cultured BMDMSC were transduced with E1-deleted adenoviral vectors containing either human BMP2 or BMP6 coding sequence under cytomegalovirus (CMV) promoter control [17:1 multiplicities of infection (moi)] and either sustained in monolayer or suspended in 1 mL 1.2% alginate beads for 22 days. Adenovirus (Ad)-BMP-2 and Ad-BMP-6 transduction resulted in abundant BMP-2 and BMP-6 mRNA and protein expression in monolayer culture and BMP-2 protein expression in alginate cultures. Ad-BMP-2 and Ad-BMP-6 transduced BMDMSC in monolayer had earlier and robust alkaline phosphatase-positive staining and mineralization and were sustained for a longer duration with better morphology scores than untransduced or Ad-beta-galactosidase-transduced cells. Ad-BMP-2- and, to a lesser degree, Ad-BMP-6-transduced BMDMSC suspended in alginate demonstrated greater mineralization than untransduced cells. Gene expression studies at day 2 confirmed an inflammatory response to the gene delivery process with upregulation of interleukin 8 and CXCL2. Upregulation of genes consistent with response to BMP exposure and osteogenic differentiation, specifically endochondral ossification and extracellular matrix proteins, occurred in BMP-transduced cells. These data support that transduction of BMDMSC with Ad-BMP-2 or Ad-BMP-6 can accelerate osteogenic differentiation and mineralization of stem cells in culture, including in three-dimensional culture. BMP-2-transduced stem cells suspended in alginate culture may be a practical carrier system to support bone formation in vivo. BMP-6 induced a less robust cellular response than BMP-2, particularly in alginate culture.

Effects of the omega-3 fatty acid, alpha-linolenic acid, on lipopolysaccharide-challenged synovial explants from horses.

OBJECTIVE: To determine the effects of pretreatment with alpha-linolenic acid, an omega-3 polyunsaturated fatty acid, on equine synovial explants challenged with lipopolysaccharide (LPS). ANIMALS: 8 mature mixed-breed horses (4 mares and 4 geldings). PROCEDURE: Synovial explants were assigned to receive 1 of 7 concentrations of alpha-linolenic acid, ranging from 0 to 300 microg/mL. At each concentration, half of the explants were controls and half were challenged with 0.003 microg of LPS as a model of synovial inflammation. Cell inflammatory response was evaluated by measurement of prostaglandin E2 production via an ELISA. Synovial cell viability, function, histomorphologic characteristics, and cell membrane composition were evaluated by use of trypan blue dye exclusion, hexuronic acid assay for hyaluronic acid, objective microscopic scoring, and high-performance liquid chromatography, respectively. RESULTS: Challenge with LPS significantly increased production of prostaglandin E2 and decreased production of hyaluronic acid. Treatment with alpha-linolenic acid at the highest dose inhibited prostaglandin E2 production. Cell viability and histomorphologic characteristics were not altered by treatment with alpha-linolenic acid or LPS challenge. Treatment with alpha-linolenic acid increased the percentage of this fatty acid in the explant cell membranes. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that investigation of alpha-linolenic acid as an anti-inflammatory medication for equine synovitis is warranted.

The effect of cranial cruciate ligament insufficiency on caudal cruciate ligament morphology: An experimental study in dogs.

OBJECTIVES: To investigate the effect of cranial cruciate ligament (CrCL) insufficiency on morphology of the canine caudal cruciate ligament (CdCL). STUDY DESIGN: In vivo experimental study. ANIMALS: Five adult foxhounds. METHODS: Two years after CrCL transection, the histologic appearance of CdCLs from CrCL-deficient and unoperated contralateral control (CrCL-intact) stifle joints were evaluated using light and transmission electron microscopy. RESULTS: CdCLs from CrCL-deficient joints had extracellular matrix changes, characterized by chondroid metaplasia and disruption of cell architecture. Percent of small-diameter fibrils in CdCLs from CrCL-deficient joints was significantly greater (P <.05) than that in CdCLs from CrCL-intact joints. Collagen fibril density in CdCLs from CrCL-deficient joints (41.09 +/- 5.39%) tended to be less than that in CdCLs from CrCL-intact joints (52.96 +/- 6.92%); however, this difference was not significant (P =.056). Mean eccentricity (ratio of minor to major diameters) of collagen fibrils was significantly (P <.0001) lower for CdCLs from CrCL-deficient joints (0.85 +/- 0.016) when compared with that for CdCLs from CrCL-intact joints (0.87 +/- 0.015). CONCLUSIONS: Significant alterations were found in the morphology of CdCLs from CrCL-deficient joints. These changes may be associated with repetitive microtrauma to the CdCL secondary to instability or enzymatic degradation in the hostile synovial environment of an unstable joint. CLINICAL RELEVANCE: Regardless of the cause, the switch to a predominantly small-diameter collagen fibril profile may reflect compromised material properties of the CdCL. This should be taken into account when considering surgical techniques that rely on the CdCL to stabilize CrCL-deficient stifles.