An Overview and Predictors of Achieving the Postoperative Ceiling Effect of the WOMAC Score Following Total Knee Arthroplasty.

BACKGROUND: To describe the ceiling effect for the components of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and identify preoperative independent predictors for patients who achieve maximal scores (ceiling effect) after total knee arthroplasty (TKA). METHODS: A retrospective cohort of 2589 patients undergoing a primary TKA were identified from an established arthroplasty database. Patient demographics, WOMAC and Short Form 12 (SF-12) scores were collected preoperatively and 1 year postoperatively. Logistic regression analysis was used to identify independent preoperative predictors of patients achieving ceiling scores. RESULTS: The ceiling effect was 26.8% (n = 695) for the pain score, 6.4% (n = 165) for the function score, and 21.2% (n = 548) for the stiffness score. Lower body mass index (P = .001), absence of gastric ulceration (P = .04), absence of anemia (P = .02), absence of depression (P = .004), and absence of back pain (P < .001) and better preoperative WOMAC pain and SF-12 physical (P = .01) and mental (P < .001) scores were associated with a ceiling WOMAC pain score. Male gender (P = .03), lower body mass index (P = .040), absence of gastric ulceration (P = .004), and absence of back pain (P < .001) and better preoperative SF-12 physical (P = .02) scores were associated with a ceiling WOMAC function score. Male gender (P = .001), absence of back pain (P < .001), and better preoperative WOMAC stiffness score (P = .005) and SF-12 mental (P = .001) scores were associated with a ceiling WOMAC stiffness score. CONCLUSION: The WOMAC pain and stiffness components demonstrated a high ceiling effect but in contrast the functional score had a low ceiling effect. The absence of back pain was a common predictive factor for all 3 components and had the greatest impact upon the likelihood of achieving a ceiling score.

What do patients know about their joint replacement implants?

BACKGROUND AND AIMS: Following a hip or knee replacement, patients may have little information about their prosthesis. This can lead to anxiety in the face of media reports about failing implants or misconceptions about how to live with a joint replacement. The aim of this study was to determine the level of understanding amongst patients who had undergone joint replacement in order to inform the development of an educational intervention. METHODS AND RESULTS: A cross-sectional, questionnaire-based survey. The survey was administered to patients attending an orthopaedic arthroplasty follow up clinic between June 2012 and October 2012. Patients were selected in a convenience sampling manner and had all undergone joint replacement at least three months prior to the survey. Responses were available from 52 patients; 49/52 (94%) of patients did not know what model of joint replacement they had and 44/52 (85%) did not know what materials the implant was made from. There was wide variation in recall of advice about activity restrictions. CONCLUSION: Whilst patients used the internet and other sources to look for advice, this survey suggests the most appropriate educational intervention for this population would involve written information including advice about type of implant, activity restrictions, dental treatment and airport security detectors.

Of dogs and men: comparative biology as a tool for the discovery of novel biomarkers and drug development targets in osteosarcoma.

The similarities between human and canine osteosarcoma with regard to histology, biological behavior and molecular genetic alterations suggest that the dog provides a supplementary model for the development and preclinical testing of novel therapeutics. Counter intuitively, careful examination of the differences between OS in the two species may also be rewarding in terms of increasing our understanding of the pathogenesis of this cancer. This review will discuss the arguments in favor of the "dog model" and outline how the evaluation of treatment strategies in dogs has indicated avenues for improvement of protocols for human patients.

Co-localisation of intra-nuclear membrane type-1 matrix metalloproteinase and hypoxia inducible factor-2α in osteosarcoma and prostate carcinoma cells.

Increased membrane type-1 matrix metalloproteinase (MT1-MMP) expression in osteosarcoma is predictive of poor prognosis and directs bone metastasis in prostate carcinoma. MT1-MMP subcellular localisation varies with oxygen tension, and, therefore, the aim of the present study was to assess protein interactions between MT1-MMP and the hypoxia inducible factors (HIF-1α and HIF-2α). MT1-MMP protein expression was investigated across a panel of cancer cell lines, including a positive and negative control. The hypoxia-induced alteration in subcellular location of MT1-MMP, HIF-1α and HIF-2α in the U2OS osteosarcoma cell line was assessed using subcellular fractionation. A proximity ligation assay was utilised to assess protein to protein interactions in the osteosarcoma U2OS and prostate carcinoma PC3 cell lines. U2OS and PC3 cells exhibited a significantly increased intra-nuclear interaction between MT1-MMP and HIF-2α in response to hypoxia. The role of this warrants further investigation as it may unveil novel opportunities to target MT1-MMP, which is of particular significance for osteosarcoma since current treatment options are limited.

A novel in vitro model to investigate behavior of articular chondrocytes in osteoarthritis.

OBJECTIVE: To investigate in vivo simulation of the microenvironment in which osteoarthritis (OA) chondrocytes are cultured in vitro. METHODS: Human articular chondrocytes were cultured under normoxic and hypoxic conditions. Cells were cultured on standard culture plastic or a porous polyHEMA surface that closely resembles the in vivo cartilage microarchitecture. Morphological changes to the cells were demonstrated by fluorescent staining with DAPI and vinculin. Proteoglycan and type II collagen protein levels were assessed using established techniques. Matrix metalloproteinase-1 (MMP-1) production was assessed by ELISA. The gene expression of type II collagen and SOX9 was measured using real-time polymerase chain reaction. RESULTS: Cells grown on culture plastic were seen to be flat and hexagonal. Cells cultured on the porous polyHEMA surface exhibited morphology in keeping with the in vivo microenvironment. Glycosaminoglycan release in hypoxia was high from cells cultured on standard culture plastic. Transcriptional expression of type II collagen was upregulated in hypoxia and by culture on the polyHEMA surface. Transcriptional expression of SOX9 in hypoxia was upregulated compared to normoxia; no significant effect was seen by varying the culture surface. Translational expression of type II collagen was upregulated at 20% oxygen on the polyHEMA surface compared to culture plastic and this was related to MMP-1 expression. CONCLUSION: Culture of chondrocytes in hypoxia and on a porous surface simulates the in vivo microenvironment and illustrates the molecular mechanisms of OA.

Injury to the lateral femoral cutaneous nerve during minimally invasive hip surgery: a cadaver study.

INTRODUCTION: A smaller skin incision as part of minimally invasive surgery (MIS) for total hip arthroplasty (THA) is thought to reduce local tissue trauma. Preservation of cutaneous nerves may reduce postoperative pain and improve rehabilitation. The standard lateral approach (SLA) and two MIS approaches (anterolateral [ALA] and posterior [PA]) were compared to determine which incision preserved cutaneous nerves. PATIENTS AND METHODS: Fifteen cadaveric hip specimens were dissected to establish the course of branches of the lateral femoral cutaneous nerve. The number of branches divided by each of the three incisions was recorded. RESULTS: The MIS incisions resulted in significantly less nerve division compared with the SLA. The mean difference between the SLA and the ALA was 4.4 (P < 0.0001), and between the SLA and the PA was 1.4 (P = 0.0005). The ALA divided significantly fewer nerves compared with the PA (mean difference = 3; P = 0.0001). DISCUSSION: There is little evidence of the benefit of one MIS approach over another in the literature. The ALA preserved significantly more cutaneous nerves in this study. These results need corroboration with clinical outcomes to determine their significance.

Venous thromboembolism in patients with primary bone or soft-tissue sarcomas.

BACKGROUND: Venous thromboembolism has been independently associated with both malignant disease and orthopaedic surgery. Patients with bone or soft-tissue tumors who undergo orthopaedic surgery may therefore be at high risk for thromboembolic events. The purpose of the present retrospective study was to determine the rate of clinically detected deep venous thrombosis and pulmonary embolism in patients with trunk or extremity bone or soft-tissue sarcomas. METHODS: The medical records of patients with a confirmed diagnosis of primary bone or soft-tissue sarcoma who had presented to our unit between 1998 and 2003 were reviewed with use of a standardized chart abstraction tool. The data that were retrieved included patient-related data (demographic characteristics, diagnoses, and surgical interventions), the use of adjuvant chemotherapy or radiation therapy, additional risk factors for thromboembolism, the use of thromboembolic prophylaxis, and confirmed thromboembolic events. RESULTS: Of the 252 patients who were identified, ninety-four had a diagnosis of primary bone sarcoma and 158 had a diagnosis of primary soft-tissue sarcoma. Approximately 70% of the cohort received thromboprophylaxis, with 57% receiving low-molecular-weight heparin. Thirty-seven patients were clinically suspected of having a deep venous thrombosis. Nine patients had a deep venous thrombosis that was confirmed radiographically, and in one case the diagnosis was made at another center, resulting in a rate of clinically evident deep venous thrombosis of 4%. Nine patients had a clinically suspected pulmonary embolism. One patient had confirmation of the pulmonary embolism with use of a ventilation-perfusion scan, one patient died of pulmonary embolism, and one patient had diagnosis of the pulmonary embolism at another center, resulting in an overall rate of pulmonary embolism of 1.2% and a rate of fatal pulmonary embolism of 0.4%. All patients with thromboembolic events had a tumor involving the hip or thigh, with the majority of the events occurring prior to definitive surgery. CONCLUSIONS: The risk of a clinically apparent thromboembolic event in patients with bone or soft-tissue sarcomas is comparable with that in other orthopaedic patients. However, tumors in the hip or thigh may be associated with a particularly high risk of thromboembolism. A prospective study is needed to investigate factors that are predictive of thromboembolism and the role of chemical thromboprophylaxis.

Large segment allograft survival is improved with intramedullary cement.

BACKGROUND AND OBJECTIVES: The most common cause of failure in large segment bone allografts used for oncologic reconstruction is allograft fracture. Reinforcement with pressurized intramedullary cement may improve the mechanical properties of allografts. METHODS: We reviewed the prospectively collected records of 45 patients who underwent en bloc resection of an extremity bone tumor and reconstruction using an allograft with intramedullary cement. RESULTS: Seven allografts were used for arthrodesis, 20 were intercalary, and 18 were osteochondral. Twenty eight of 45 patients were alive at a mean 5.8 years (SD 1.9; range 3-11.2) with 24 allografts in situ. In these 45 patients, there were four allograft fractures and four infections. Six of these complications resulted in allograft removal. The estimated 5-year allograft survival rate was 86% (95% confidence interval 74-98%). Seven patients required secondary autogenous bone grafting for non-unions. Function measured by the Toronto Extremity Salvage Score and the 1987 and 1993 Musculoskeletal Tumor Society Rating Scales demonstrated a consistent pattern with worse function in patients with osteochondral allografts and best function with intercalary allografts. CONCLUSIONS: These results suggest the addition of intramedullary cement to large segment bone allografts improves their survival by decreasing the fracture risk, particularly for allografts used for arthrodesis and intercalary reconstructions.

The influence of anatomic location on outcome in patients with soft tissue sarcoma of the extremity.

BACKGROUND: The anatomic location of an extremity soft tissue sarcoma may influence the patient's presentation, management, and local and systemic recurrence rates. The objective of this study was to compare the presentation, management, and outcome of patients with soft tissue sarcomas of the upper extremity and the lower extremity. METHODS: Prospectively collected data from patients who underwent limb-sparing surgery for extremity soft tissue sarcoma between January, 1986 and April, 1997 were analyzed. Local recurrence free rates and metastasis free rates were calculated using the method of Kaplan and Meier. Univariate and multivariate analyses of potential predictive factors were evaluated with the log-rank test and the Cox proportional hazards model. RESULTS: Of 480 eligible patients, 48 patients (10.0%) had a local recurrence, and 131 patients (27.3%) developed distant metastasis. The median follow-up of survivors was 4.8 years (range, 0.1-12.9 years). Patients with upper extremity tumors had smaller lesions (6.0 cm vs. 9.3 cm; P < 0.001), more often underwent unplanned excision before referral (89 patients [64.0%] vs. 160 patients [46.9%]; P < 0.001), and less often received radiotherapy (98 patients [70.5%] vs. 289 patients [84.8%]; P < 0.001). The 5-year local recurrence free rate was 82% for patients with sarcomas of the upper extremity and 93% for patients with sarcomas of the lower extremity (P = 0.002). The 5-year metastasis free rate was 82% for patients with sarcomas of the upper extremity and 69% for patients with sarcomas of the lower extremity (P = 0.013). CONCLUSIONS: Local recurrence was more frequent in patients who had sarcomas of the upper extremity compared with patients who had sarcomas of the lower extremity. Factors that contributed to this difference included histologic type, the use of radiotherapy, and local anatomy. Metastasis was more frequent among patients with sarcomas of the lower extremity, because those tumors tended to be large and deeper compared with upper extremity tumors.