Viscosupplementation with hyaluronic acid in the treatment for cartilage lesions: a review of current evidence and future directions.

Diseases involving the articular cartilage are one of the leading causes of physical impairment among the adult population. While surgical technique and advancement have allowed us effective means at treating these diseases, this is not without significant risk and morbidity. With a very solid safety profile, viscosupplementation with hyaluronic acid (HA) derivatives has become an excellent modality for treating diseased articular cartilage. Recent literature supports the use of HA not only in the management of the pain associated with osteoarthritis but also as a disease-modifying agent as well. Further studies have started to define exciting new roles for viscosupplementation in the treatment for acute injuries to the joint microenvironment.

Clinical outcomes following repair of the pars interarticularis.

Spondylolysis is a source of back pain in adolescents and young adults. The purpose of this study was to report clinical outcomes in 49 patients treated with isolated motion-sparing repair of the pars interarticularis. Patients who underwent direct repair of the pars interarticularis between 2002 and 2009 were identified. Standard demographic and radiographic data, needed for further surgeries, and radiographic evidence of healing were collected. Of 49 patients with 90 total pars defects (41 bilateral, 8 unilateral), 7 required reoperation. No serious complications were seen. None of the risk factors analyzed in our study were predictive of reoperation. The strongest preoperative predictor of Oswestry Disability Index score was Fujii chronicity (P = .041). Motion segment sparing repair of the pars is a safe and effective procedure for refractory cases of spondylolysis.

"Figure 8" single socket double bundle ACL technique.

Using single femoral and tibial tunnels, we describe a technique of anatomically recreating the anteromedial and posterolateral anterior cruciate ligament (ACL) bundles. Transtibial, flexible reamers are utilized to create a "Figure 8" notched tunnel thereby recreating the anatomic footprint of the femoral insertion of the ACL. Rotational control of the individual bundles is created via the notched tunnel and each bundle is tensioned to 80 N individually. Anatomic double bundle ACL reconstruction is created in a reproducible modified single-bundle technique without the inherent risks associated with drilling four tunnels.

Motion segment-sparing repair of symptomatic chronic pars defects.

OBJECT: The current standard of care for symptomatic chronic spondylolysis (SP) is a one-level posterior spinal fusion for defects at L-5 or direct pars repair (motion segment sparing) for more rostral SP in younger patients and if no disc degeneration or listhesis is present. Since many patients with SP undergoing operative repair are young, a procedure with the lowest biomechanical profile is desirable, and direct pars repair is recommended. The authors here explore the limits of direct pars repair. METHODS: A retrospective review of all patients who underwent direct repair of SP between 2002 and 2009 was performed. Data were analyzed for predictors of symptom relief and radiographic fusion failure. RESULTS: Of 49 patients, only 7 required a reoperation to treat clinical symptoms, and 6 of them were female (p = 0.049). In all cases of treatment failure, the patient had bilateral L-5 SP. Patients with a slip percentage as high as 30% experienced radiographic fusion and symptom relief. Disc degeneration (measured using the Modified Pfirrmann Scale) did not predict symptom persistence or radiographic fusion failure. Patients with high-grade disc disease experienced symptom relief. The authors found no predictors of treatment failure. CONCLUSIONS: The number of patients undergoing motion segment-sparing fusions of symptomatic chronic SP can be safely increased to include patients with Grade I spondylolisthesis as well as high-grade disc disease. Female patients with bilateral L-5 SP and low lordotic angles may be better served by a posterior spinal fusion from L-5 to S-1.

Hip dislocations--epidemiology, treatment, and outcomes.

Traumatic dislocations of the hip appear to be on the rise in North America. Multidetector CT, hip arthroscopy, and high field MRI have further defined the pathoanatomy of hip dislocations. They can be divided into simple and complex dislocations. At the University of Louisville, an algorithm has been developed to facilitate rapid and accurate diagnosis and treatment of simple hip dislocations. In contrast to the treatment of simple hip dislocations, the treatment of complex hip dislocations (fracture-dislocations) is generally predicated on specific treatments of the associated fracture (e.g., femoral head fracture, femoral neck fracture, acetabular fracture, etc.). This review includes the mechanism of injury, epidemiology, associated injuries, evaluation, treatment, and functional outcomes of simple hip dislocations.

Neurofibromin-deficient Schwann cells have increased lysophosphatidic acid dependent survival and migration-implications for increased neurofibroma formation during pregnancy.

Neurofibromas are the clinical hallmark of neurofibromatosis Type 1 (NF1), a genetic disorder caused by mutations of the NF1 tumor suppressor gene, which encodes neurofibromin that functions as a GTPase activating protein (GAP) for Ras. During pregnancy, up to 50% of existing neurofibromas enlarge and as many as 60% of new neurofibromas appear for the first time. Lysophosphatidic acid (LPA) is a prototypic lysophospholipid that modulates cell migration and survival of Schwann cells (SCs) and is made in increasing concentrations throughout pregnancy. We addressed the influence of LPA on the biochemical and cellular functions of SCs with a homozygous mutation of the murine homologue of the NF1 gene (Nf1-/-). LPA promoted F-actin polymerization and increased migration and survival of Nf1-/- SCs as compared to wild type (WT) SCs. Furthermore, LPA induced a higher level of Ras-GTP and Akt phosphorylation in Nf1-/- SCs as compared to WT cells. Pharmacologic inhibition or siRNA for the p85beta regulatory subunit of Class I A PI3-K significantly reduced LPA-induced Schwann cell survival and migration. Introduction of NF1-GRD reconstitution was sufficient to normalize the LPA-mediated motility of Nf1-/- SCs. As LPA modulates excessive cell survival and motility of Nf1-/- SCs, which are the tumorigenic cells in NF1, targeting PI3-K may be a potential therapeutic approach in diminishing the development and progression of neurofibromas in pregnant women with NF1.

Nf1+/- mast cells induce neurofibroma like phenotypes through secreted TGF-beta signaling.

Neurofibromas are common tumors found in neurofibromatosis type 1 (NF1) patients. These complex tumors are composed of Schwann cells, mast cells, fibroblasts and perineurial cells embedded in collagen that provide a lattice for tumor invasion. Genetic studies demonstrate that in neurofibromas, nullizygous loss of Nf1 in Schwann cells and haploinsufficiency of Nf1 in non-neuronal cells are required for tumorigenesis. Fibroblasts are a major cellular constituent in neurofibromas and are a source of collagen that constitutes approximately 50% of the dry weight of the tumor. Here, we show that two of the prevalent heterozygous cells found in neurofibromas, mast cells and fibroblasts interact directly to contribute to tumor phenotype. Nf1+/- mast cells secrete elevated concentrations of the profibrotic transforming growth factor-beta (TGF-beta). In response to TGF-beta, both murine Nf1+/- fibroblasts and fibroblasts from human neurofibromas proliferate and synthesize excessive collagen, a hallmark of neurofibromas. We also establish that the TGF-beta response occurs via hyperactivation of a novel Ras-c-abl signaling pathway. Genetic or pharmacological inhibition of c-abl reverses fibroblast proliferation and collagen synthesis to wild-type levels. These studies identify a novel molecular target to inhibit neurofibroma formation.

Neurofibromin-deficient Schwann cells secrete a potent migratory stimulus for Nf1+/- mast cells.

The NF1 tumor suppressor gene encodes a GTPase-activating protein called neurofibromin that negatively regulates Ras signaling. Mutations in NF1 cause neurofibromatosis type 1 (NF1). The development of neurofibromas, which are complex tumors composed of multiple cell types, is a hallmark of NF1. Somatic inactivation of murine Nf1 in Schwann cells is necessary, but not sufficient, to initiate neurofibroma formation. Neurofibromas occur with high penetrance in mice in which Nf1 is ablated in Schwann cells in the context of a heterozygous mutant (Nf1+/-) microenvironment. Mast cells infiltrate neurofibromas, where they secrete proteins that can remodel the ECM and initiate angiogenesis. Thus, identification of mechanisms responsible for mast cell migration to tumor microenvironments is important for understanding tumorigenesis and for designing potential therapies. Here, we show that homozygous Nf1 mutant (Nf1-/-) Schwann cells secrete Kit ligand (KitL), which stimulates mast cell migration, and that Nf1+/- mast cells are hypermotile in response to KitL. Furthermore, we link hyperactivation of the Ras-class IA-PI3K-Rac2 pathway to increased Nf1+/- mast cell migration. Thus, these studies identify a novel interaction between Nf1-/- Schwann cells and Nf1+/- mast cells that is likely to be important in neurofibroma formation.