Faculty Bibliography

OBJECTIVE: ANXA6, the gene for annexin A6, is highly expressed in osteoarthritic (OA) articular chondrocytes but not in healthy articular chondrocytes. This study was undertaken to determine whether annexin A6 affects catabolic events in these cells. METHODS: Articular chondrocytes were isolated from Anxa6-knockout mice, wild-type (WT) mice, and human articular cartilage in which ANXA6 was overexpressed. Cells were treated with interleukin-1beta (IL-1beta) or tumor necrosis factor alpha (TNFalpha), and expression of catabolic genes and activation of NF-kappaB were determined by real-time polymerase chain reaction and luciferase reporter assay. Anxa6(-/-) and WT mouse knee joints were injected with IL-1beta or the medial collateral ligament was transected and partial resection of the medial meniscus was performed to determine the role of Anxa6 in IL-1beta-mediated cartilage destruction and OA progression. The mechanism by which Anxa6 stimulates NF-kappaB activity was determined by coimmunoprecipitation and immunoblot analysis of nuclear and cytoplasmic fractions of IL-1beta-treated Anxa6(-/-) and WT mouse chondrocytes for p65 and Anxa6. RESULTS: Loss of Anxa6 resulted in decreased NF-kappaB activation and catabolic marker messenger RNA (mRNA) levels in IL-1beta- or TNFalpha-treated articular chondrocytes, whereas overexpression of ANXA6 resulted in increased NF-kappaB activity and catabolic marker mRNA levels. Annexin A6 interacted with p65, and loss of Anxa6 caused decreased nuclear translocation and retention of the active p50/p65 NF-kappaB complex. Cartilage destruction in Anxa6(-/-) mouse knee joints after IL-1beta injection or partial medial meniscectomy was reduced as compared to that in WT mouse joints. CONCLUSION: Our data define a role of annexin A6 in the modulation of NF-kappaB activity and in the stimulation of catabolic events in articular chondrocytes.

Despite advances in thromboprophylaxis, venous thromboembolism remains a significant problem in major orthopaedic surgery, associated with significant morbidity and high cost of treatment. Virchow's triad, as well as patient and procedural risk factors, put many orthopaedic surgery patients at high risk. Diagnosis is based on clinical suspicion in combination with imaging such as ultrasound. Options for prophylaxis include aspirin, warfarin, low-molecular weight heparins and direct inhibitors of coagulation factors. In this review, we discuss the latest American Academy of Orthopaedic Surgeons (AAOS) and American College of Chest Physicians (ACCP) guidelines for prevention of venous thromboembolism and their implications for practice. 1940-7041 2013 Wolters Kluwer Health

The aim of this retrospective study was to identify risk factors for hospital-acquired Clostridium difficile infection (HA-CDI) in orthopaedic patients. Thirty-two HA-CDI cases were each matched with two controls. Incidence rate was 0.33 cases per 1000 patient-days. Univariate analyses showed that surgery >24 h after admission, antibiotics for treatment, and proton pump inhibitors were associated with HA-CDI. Multivariate analyses revealed that surgery >24 h after admission was associated with HA-CDI. Patients hospitalized before surgery had a greater risk of HA-CDI, suggesting opportunities to reduce environmental exposure to C. difficile by timelier preoperative medical optimization in the outpatient setting.

BACKGROUND: There is still little known regarding the effects of meniscus resection size on tibiofemoral stability. PURPOSE: To determine if partial medial meniscectomy of the posterior horn significantly alters tibiofemoral stability as measured by the anterior-posterior (AP) position and laxity of the medial femoral condyle. STUDY DESIGN: Controlled laboratory study. METHODS: Five cadaveric knees were dissected to the capsule, preserving all ligaments and the quadriceps tendon. Each specimen was first tested on a rig where the AP position and laxity of the medial femoral condyle were measured while a range of forces was applied from full extension to 90 degrees of flexion. Magnetic resonance imaging (MRI) at 3 tesla was then performed for baseline measurements of the meniscus before partial meniscectomy. Arthroscopic partial medial meniscectomy aimed at 30% of the posterior horn was then performed, followed by repeat mechanical testing and MRI. The sequence was then repeated for arthroscopic partial meniscectomy aimed at 60% and 100% of the posterior horn of the medial meniscus. RESULTS: The MRI analysis demonstrated that 22% +/- 9% of the original width of the posterior horn was removed at the first resection, 46% +/- 11% was removed at the second resection, and the third resection was 100% removal of the posterior horn for all specimens. After 22% resection, no significant difference in AP laxity was observed. A statistically significant increase in AP laxity was observed with 46% resection under a 500-N compressive load compared with the intact meniscus. After full resection, significant increases in AP laxity were observed under a 50-N compressive load compared with the intact and 22% and 46% resections. The 22% resection had similar AP positions as the intact knee, whereas the 46% resection and 100% removal of the posterior horn had statistically further posterior AP positions than the intact knee. CONCLUSION: Partial medial meniscectomy with >/=46% resection of the original width of the posterior horn significantly altered the AP position of the medial femoral condyle and also increased laxity. CLINICAL RELEVANCE: These mechanical changes may lead to abnormal cartilage loading and early osteoarthritis.

Management of traumatic soft-tissue injuries remains a challenging and ever evolving field within orthopedic surgery. The basic principle of addressing life before limb in the initial assessment of critically injured patients has not changed. Although arteriography remains the gold standard for vascular injury screening, computed tomography angiography is being used more often to determine limb viability, and its sensitivity and specificity for detecting vascular lesions are reported to be excellent. Thorough debridement and irrigation with early institution of antibiotics are crucial in preventing infection; debridement should be performed urgently once life-threatening conditions have been addressed. Increasing use of vacuum-assisted closure therapy has created a trend down the reconstructive ladder, with improvements in resulting wound closure. Although the orthoplastics approach and new microsurgical techniques have made limb salvage possible in even the most severely injured extremities, it is important to clearly identify the zone of injury and to inform patients and their families of the outcomes of limb salvage versus amputation. Results from the LEAP (Lower Extremity Assessment Project) trials and similar studies should guide orthopedic surgeons in the management of these complex injuries. Nevertheless, it is important to individualize management plans according to patient factors.

Pulmonary metastasis remains the leading ca use of death for cancer patients. Opportunities to improve treatment outcomes for patients require new methods to study and view the biology of metastatic progression. Here, we describe an ex vivo pulmonary metastasis assay (PuMA) in which the metastatic progression of GFP-expressing cancer cells, from a single cell to the formation of multicellular colonies, in the mouse lung microenvironment was assessed in real time for up to 21 days. The biological validity of this assay was confirmed by its prediction of the in vivo behavior of a variety of high- and low-metastatic human and mouse cancer cell lines and the discrimination of tumor microenvironments in the lung that were most permissive to metastasis. Using this approach, we provide what we believe to be new insights into the importance of tumor cell interactions with the stromal components of the lung microenvironment. Finally, the translational utility of this assay was demonstrated through its use in the evaluation of therapeutics at discrete time points during metastatic progression. We believe that this assay system is uniquely capable of advancing our understanding of both metastasis biology and therapeutic strategies.

We present the case of a patient with malignant transformation of a liposclerosing myxofibrous tumor. The patient had a histologically confirmed liposclerosing myxofibrous tumor that, during a course of 22 months, spontaneously transformed into a lesion appearing like a benign giant cell reactive lesion and subsequently into a high-grade bone sarcoma. Few such cases of spontaneous malignant transformation of liposclerosing myxofibrous tumor have been reported. We report what we believe to be the first case documenting spontaneous transformation of a liposclerosing myxofibrous tumor into an intermediate lesion with benign-appearing histologic features and then into a high-grade malignant tumor.