Faculty Bibliography

CONTEXT: Venous thromboembolic (VTE) disease is thought to be an uncommon but serious problem after anterior cruciate ligament (ACL) reconstruction. Rates of VTE after ACL reconstruction are not well documented. OBJECTIVE: To determine the rates of deep vein thrombosis (DVT) and symptomatic pulmonary emboli (PE) after ACL reconstruction. DATA SOURCES: Five publicly available databases (PubMed, Cochrane Database of Systematic Reviews, Scopus, Embase, and CINAHL Complete) were utilized. STUDY SELECTION: All studies that screened patients for DVT and reported rates of DVT and PE after ACL reconstruction were eligible for inclusion. Level 5 evidence, cadaver, biomechanical, and basic science studies; studies reporting only multiligament reconstruction outcomes; studies where rates of DVT and PE could not be separated out from patients undergoing other types of arthroscopic knee procedures; and classification studies were excluded. STUDY DESIGN: Systematic review. LEVEL OF EVIDENCE: Level 4. DATA EXTRACTION: All study, subject, and surgical data were analyzed. Descriptive statistics were calculated. RESULTS: Six studies met the inclusion criteria, with a mean Modified Colman Methodology Score of 30 +/- 8.22. A total of 692 patients (488 men [70.5%]; mean age, 31.6 +/- 2.82 years; mean follow-up, 7 +/- 18.4 months) underwent ACL reconstruction using either semitendinosus-gracilis autograft (77.6%), bone-patellar tendon-bone (BTB) autograft (22%), or allograft (0.4%). No patient received postoperative pharmacological anticoagulation. Fifty-eight patients (8.4%) had a DVT (81% below knee and 19% above knee), while only 1 patient (0.2%) had a symptomatic PE. When reported, 27% of DVT episodes were symptomatic. CONCLUSION: The rate of DVT after ACL reconstruction in patients who did not receive postoperative pharmacological anticoagulation is 8.4%, while the rate of symptomatic PE is 0.2%. Of the DVT episodes that occurred, 73% were asymptomatic.

A thorough knowledge of the principles of antibiotic stewardship is a crucial part of high-quality orthopaedic surgical care. These principles include (1) determining appropriate indications for antibiotic administration, (2) choosing the correct antibiotic based on known or expected pathogens, (3) determining the correct dosage, and (4) determining the appropriate duration of treatment. Antibiotic stewardship programs have a multidisciplinary staff that can help guide antibiotic selection and dosage. These programs also perform active surveillance of antimicrobial use and may reduce Clostridium difficile and other drug-resistant bacterial infections by providing expert guidance on judicious antibiotic usage. The emergence of antibiotic-resistant pathogens, the geographical diversity of these infecting pathogens, and the changing patient population require customization of prophylactic regimens to reduce infectious complications. A multidisciplinary approach to antibiotic stewardship can lead to improved patient outcomes and cost-effective medical care.

CONTEXT: Skeletal muscle is comprised of a highly organized network of cells, neurovascular structures, and connective tissue. Muscle injury is typically followed by a well-orchestrated healing response that consists of the following phases: inflammation, regeneration, and fibrosis. This review presents the mechanisms of action and evidence supporting the effectiveness of various traditional and novel therapies at each phase of the skeletal muscle healing process. EVIDENCE ACQUISITION: Relevant published articles were identified using MEDLINE (1978-2013). STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 3. RESULTS: To facilitate muscle healing, surgical techniques involving direct suture repair, as well as the implantation of innovative biologic scaffolds, have been developed. Nonsteroidal anti-inflammatory drugs may be potentially supplanted by nitric oxide and curcumin in modulating the inflammatory pathway. Studies in muscle regeneration have identified stem cells, myogenic factors, and beta-agonists capable of enhancing the regenerative capabilities of injured tissue. Furthermore, transforming growth factor-beta1 (TGF-beta1) and, more recently, myostatin and the rennin-angiotensin system have been implicated in fibrous tissue formation; several antifibrotic agents have demonstrated the ability to disrupt these systems. CONCLUSION: Effective repair of skeletal muscle after severe injury is unlikely to be achieved with a single intervention. For full functional recovery of muscle there is a need to control inflammation, stimulate regeneration, and limit fibrosis. STRENGTH-OF-RECOMMENDATION TAXONOMY SORT: B.

OBJECTIVE: To determine the role of ANK/Myb-binding protein 1a (MYBBP1a) and sphingosine kinase 1 (SPHK1) interactions in catabolic events of articular chondrocytes. METHOD: ANK/MYBBP1a and SPHK1 interactions were identified using yeast two-hybrid screening and co-immunoprecipitation. To determine the role of these interactions in catabolic events of articular chondrocytes, ank/ank and wild type mouse chondrocytes transfected with full-length or mutant ank expression vectors or femoral heads were treated with interleukin-1beta (IL-1beta) in the absence or presence of SPHK inhibitor. Catabolic marker mRNA levels were analyzed by real time PCR; proteoglycan loss using safranin O staining and MMP-13 immunostaining were determined in femoral head explants; NF-kappaB activity was determined by transfecting chondrocytes with a NF-kappaB-specific luciferase reporter and analyzing nuclear translocation of p65 by immunoblotting; MYBBP1a nuclear or cytoplasmic amounts were determined by immunohistochemistry and immunoblotting. RESULTS: The ANK N-terminal region interacted with SPHK1, whereas a cytoplasmic C-terminal loop interacted with MYBBP1a. Lack of ANK/MYBBP1a and SPHK1 interactions in ank/ank chondrocytes resulted in increased MYBBP1a nuclear amounts and decreased SPHK1 activity, and consequently decreased NF-kappaB activity, catabolic marker mRNA levels, proteoglycan loss, and MMP-13 immunostaining in IL-1beta-treated articular chondrocytes or femoral heads. Transfection with full-length ank expression vector reduced nuclear MYBBP1a amounts and fully restored SPHK and NF-kappaB activities in IL-1beta-treated ank/ank chondrocytes, whereas transfection with P5L or F376del mutant ank reduced nuclear MYBBP1a or increased SPHK activity, respectively, and consequently either transfection only partially restored NF-kappaB activity. CONCLUSION: ANK/MYBBP1a and SPHK1 interactions stimulate catabolic events in IL-1beta-mediated cartilage degradation.

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