Faculty Bibliography

This study was designed to characterize the synovium in the joints of Charcot neuroarthropathy (CNA) and investigate the potential role of fibroblast-like synoviocytes (FLS) in the pathology of CNA. Synovial samples were collected from CNA patients (n = 7) and non-CNA patients (n = 7), for control, during orthopaedic procedures and used for histology and isolation of FLS. Histological characterization of synovium included innervation and FLS localization. The isolated FLS from the CNA and non-CNA synovium were cultured, with or without tumor necrosis factor-α (TNF-α), for evaluation of invasiveness, gene expression, and cartilage degradation. Vasoactive intestinal peptide (VIP), a neuropeptide, was supplemented into the co-cultures of FLS and cartilage explants. Compared with the non-CNA synovium, CNA synovium was highly inflammatory, with reduced innervation and intense expression of cadherin-11. The FLS isolated from CNA synovium, particularly when activated with TNF-α, were more invasive, increased the expression of ADAMTS4, IL-6, and RANKL, and depleted proteoglycans from cartilage explants when they were co-cultured. Addition of VIP into the culture medium neutralized the catabolic effect of the CNA FLS on cartilage explants. In conclusion, FLS plays an important role in the pathology of CNA. Therapies targeting synovium and FLS may prevent or treat the joint destruction in CNA.

Intramedullary screw fixation has become widely accepted as the standard of care for operative treatment of Jones fractures, allowing not only accelerated rehabilitation but also reduction of the risk of repeat fracture. The unique anatomy of the fifth metatarsal--mainly its inherent lateral curvature--makes fixation technically challenging. In general, surgical fixation should be performed with the largest screw possible, in both diameter and length, which will provide the strongest possible construct. However, an increased screw length and width have been associated with complications, including lateral gapping and distraction of the fracture site and malreduction of the fracture. The use of a pointed reduction clamp is a simple, yet effective, method of preventing iatrogenic displacement and gapping at the fracture site during placement of an intramedullary screw. Percutaneous reduction and stabilization of the fracture using this technique could help limit the complications associated with large screw fixation of Jones fractures.

BACKGROUND:The foot fat pad (FFP) bears body weight and may become a source of foot pain during aging. This study investigated the regenerative effects of autologous adipose tissue-derived mesenchymal stem cells (AT-MSCs) in the FFP of rats. METHODS:Fat tissue was harvested from a total of 30 male Sprague-Dawley rats for isolation of AT-MSCs. The cells were cultured, adipogenic differentiation was induced for 1 week, and the AT-MSCs were labeled with fluorescent dye before injection. AT-MSCs (5 × 10(4) in 50 µL of saline) were injected into the second infradigital pad in the right hindfoot of the rat of origin. Saline only (50 µL) was injected into the corresponding fat pad in the left hind paw of each rat. Rats (n = 10) were euthanized at 1, 2, and 3 weeks, and the second infradigital fat pads were dissected for histologic examination. RESULTS:The fluorescence-labeled AT-MSCs were present in the foot pads throughout the 3-week experimental period. On histologic testing, the area of fat pad units (FPUs) in the fat pads that received AT-MSC injections was greater than that in the control fat pads. Although the thickness of septae was not changed by AT-MSC injections, the density of elastic fibers in the septae was increased in the fat pads with implanted AT-MSCs. CONCLUSION/CONCLUSIONS:In this short-term study, the implanted AT-MSCs largely survived and might have stimulated the expansion of individual FPUs and increased the density of elastic fibers in the FFP in this rat model. CLINICAL RELEVANCE/CONCLUSIONS:These data support the development of stem cell therapies for age-associated degeneration in FFP in humans.

PURPOSE/OBJECTIVE:Optimal treatment of acute Achilles tendon ruptures remains controversial. Positive results using stem-cell-bearing concentrates have been reported with other soft-tissue repairs, but no studies exist on outcomes of bone marrow aspirate concentrate (BMAC) augmentation in primary Achilles tendon repair. METHODS:We reviewed patients with sport-related Achilles tendon ruptures treated via open repair augmented with BMAC injection from 2009 to 2011. Data on operative complications, strength, range of motion, rerupture, calf circumference and functional improvement through progressive return to sport and the Achilles tendon Total Rupture Score (ATRS) were analysed. RESULTS:A total of 27 patients (28 tendons) treated with open repair and BMAC injection were identified (mean age 38.3 ± 9.6 years). At mean follow-up of 29.7 ± 6.1 months, there were no reruptures. Walking without a boot was at 1.8 ± 0.7 months, participation in light activity was at 3.4 ± 1.8 months and 92% (25 of 27) of patients returned to their sport at 5.9 ± 1.8 months. Mean ATRS at final follow-up was 91 (range 72-100) points. One case of superficial wound dehiscence healed with local wound care. No soft-tissue masses, bone formation or tumors were observed in the operative extremity. CONCLUSIONS:Excellent results, including no re-ruptures and early mobilisation, were observed in this small cohort with open Achilles tendon repair augmented by BMAC. No adverse outcomes of biologic treatment were observed with this protocol. The efficacy of BMAC in the operative repair of acute Achilles tendon ruptures warrants further study. LEVEL OF EVIDENCE/METHODS:IV - Therapeutic.

OBJECTIVES/OBJECTIVE:This study aimed to investigate the pathology occurring at the calcified zone of articular cartilage (CZC) in the joints afflicted with post-traumatic osteoarthritis (PTOA). METHODS:Rats underwent bilateral anterior cruciate ligament (ACL) transection and medial meniscectomy to induce PTOA. Sham surgery was performed on another five rats to serve as controls. The rats were euthanized after four weeks of surgery and tibial plateaus were dissected for histology. The pathology of PTOA, CZC area and the tidemark roughness at six pre-defined locations on the tibial plateaus were quantified by histomorphometry. RESULTS:PTOA developed in the knees, generally more severe at the medial plateau than the lateral plateau, of rats in the experimental group. The CZC area was unchanged in the PTOA joints, but the topographic variations of CZC areas that presented in the control knees were reduced in the PTOA joints. The tidemark roughness decreased in areas of the medial plateau of PTOA joints and that was inversely correlated with the Mankin's score of PTOA pathology. CONCLUSION/CONCLUSIONS:Reduced tidemark roughness and unchanged CZC area differentiate PTOA from primary osteoarthritis, which is generally believed to have the opposite pathology at CZC, and may contribute to the distinct disease progression of the two entities of arthropathy.

The management of posterior tibial tendon dysfunction in adults has evolved substantially, and controversy persists regarding a specific recommended algorithm for treatment. The current focus is on early diagnosis and treatment of this disorder with joint-sparing surgeries, such as corrective osteotomies and tendon transfers, when nonsurgical modalities have been exhausted. It is helpful to be familiar with the pertinent pathophysiology and diagnostic pearls associated with posterior tibial tendon dysfunction, its treatment options, pertinent literature, and technique tips for the procedures currently being used.

BACKGROUND:There is a paucity of research on posttraumatic ankle arthritis (PTAA). We aimed to identify synovial fluid PTAA biomarkers using cytokine analysis and metabolic profiling. METHODS:Ankle joint synovial fluid was obtained from 20 patients with PTAA and 20 patients with no ankle pain and no radiographic evidence of ankle arthritis (control group). Synovial fluid samples were analyzed for IFN-γ, TNF-α, MIP-1β, MCP-1, IL-1β, IL-1Ra, IL-4, IL-6, IL-8, IL-10, IL-13, and IL-15 using ELISA and for more than 3000 metabolites using liquid and gas chromatography with mass spectroscopy. To compare presence of cytokines and metabolites between groups, t tests were used. Random forest analysis was performed on metabolites to determine whether control and PTAA samples could be differentiated based on metabolic profile. RESULTS:IL-1Ra, IL-6, IL-8, IL-10, IL-15, and MCP-1 were significantly elevated in the PTAA group. In addition, 107 metabolites in the PTAA group were significantly altered, including derangement in amino acid, carbohydrate, lipid, and energy metabolism, extracellular matrix turnover, and collagen degradation. Random forest analysis yielded a predictive accuracy of 90% when using the metabolic profiles to distinguish between control and PTAA samples. CONCLUSION/CONCLUSIONS:This study identified inflammatory cytokines and metabolites present in the synovial fluid of PTAA. CLINICAL RELEVANCE/CONCLUSIONS:Several of these entities have previously been implicated in rheumatoid arthritis and osteoarthritis of the knee, but many could potentially be used as novel biomarkers of PTAA. Most importantly, the findings suggest that metabolites could be used to distinguish synovial fluid from patients with PTAA.