Identification of the landmark registration safe zones during total knee arthroplasty using an imageless navigation system.

Incorrect registration during computer assisted total knee arthroplasty (CA-TKA) leads to malposition of implants. Our aim was to evaluate the tolerable error in anatomic landmark registration. We incorrectly registered the femoral epicondyles, femoral and tibial centers, as well as the malleoli and documented the change in angulation or rotation. We found that the distal femoral epicondyles were the most difficult anatomic landmarks to register. The other bony landmarks were more forgiving. Identification of the distal femoral epicondyles has a high inter-observer and intra-observer variability. Our observation that there is less than 2mm of safe zone in the anterior or posterior direction during registration of the medial and lateral epicondyles may explain the inability of CA-TKA to improve upon the outcomes of conventional TKA.

The oncogene LRF is a survival factor in chondrosarcoma and contributes to tumor malignancy and drug resistance.

Chondrosarcoma is a form of malignant skeletal tumor of cartilaginous origin. The non-malignant form of the disease is termed chondroma. Correctly distinguishing between the two forms is essential for making therapeutic decisions. However, due to their similar histological appearances and the lack of a reliable diagnostic marker, it is often difficult to distinguish benign tumors from low-grade chondrosarcoma. Therefore, it is necessary to search for a potential marker that has diagnostic and prognostic values in chondrosarcoma. In this study, we demonstrated by immunohistochemistry that elevated leukemia/lymphoma-related factor (LRF) expression was associated with increased malignancy in human chondrosarcoma tissue microarrays. Moreover, siRNA depletion of LRF drastically reduced proliferation of chondrosarcoma cell lines and effectively induced senescence in these cells. This could be attributed to the observation that LRF-depleted cells were arrested at the G(1) phase, and had increased p53 and p21 expression. Moreover, LRF depletion not only drastically reduces the cellular migration and invasion potentials of chondrosarcoma cells but also sensitized these cells to the apoptosis-inducing chemotherapeutic agent doxorubicin. We conclude that LRF is a survival factor in chondrosarcomas and its expression correlates with tumor malignancy and chemoresistance. Our data implicate the potential role of LRF as both a diagnostic marker and therapeutic target for chondrosarcomas.

Enhanced activity of transforming growth factor ß1 (TGF-ß1) bound to cartilage oligomeric matrix protein.

Cartilage oligomeric matrix protein (COMP) is an important non-collagenous cartilage protein that is essential for the structural integrity of the cartilage extracellular matrix. The repeated modular structure of COMP allows it to "bridge" and assemble multiple cartilage extracellular matrix components such as collagens, matrilins, and proteoglycans. With its modular structure, COMP also has the potential to act as a scaffold for growth factors, thereby affecting how and when the growth factors are presented to cell-surface receptors. However, it is not known whether COMP binds growth factors. We studied the binding interaction between COMP and TGF-ß1 in vitro and determined the effect of COMP on TGF-ß1-induced signal transduction in reporter cell lines and primary cells. Our results demonstrate that mature COMP protein binds to multiple TGF-ß1 molecules and that the peak binding occurs at slightly acidic pH. These interactions were confirmed by dual polarization interferometry and visualized by rotary shadow electron microscopy. There is cation-independent binding of TGF-ß1 to the C-terminal domain of COMP. In the presence of manganese, an additional TGF-ß-binding site is present in the TSP3 repeats of COMP. Finally, we show that COMP-bound TGF-ß1 causes increased TGF-ß1-dependent transcription. We conclude that TGF-ß1 binds to COMP and that TGF-ß1 bound to COMP has enhanced bioactivity.

Comparison of surgical outcomes and implant wear between ceramic-ceramic and ceramic-polyethylene articulations in total hip arthroplasty.

The results of a prospective multicenter trial comparing 357 hips randomized to total hip arthroplasty with either ceramic-ceramic or ceramic-polyethylene couplings are presented. No statistically significant difference in clinical outcomes scores between the ceramic-ceramic and ceramic-polyethylene groups was observed at any time interval. The mean linear rate was statistically lower (P < .001) in the ceramic-ceramic group (30.5 µm/year) when compared with the ceramic-polyethylene group (218.2 µm/year). The rates of ceramic implant fracture (2.6%) and audible component-related noise (3.1%) were statistically higher in the ceramic-ceramic group when compared with the ceramic-polyethylene group (P < .05). Lastly, there was no statistically significant difference in the dislocation or revision rate between the groups at the time of last clinical follow-up.

Fracture of fully coated echelon femoral stems in revision total hip arthroplasty.

Three cases of fractured uncemented, fully porous Echelon femoral stems (Smith & Nephew, Memphis, Tenn) are examined. Fracture of these components, an uncommon complication of revision hip surgery, is thought to result from cantilever bending after distal bony ingrowth. The stems in these cases fractured at 11, 22, and 28 months after revision surgery. Risk factors include increased body weight, excessive activity, an undersized stem, varus alignment, inadequate proximal femoral bone stock, and metallurgic defects. Extraction can be difficult and is often accomplished with the use of multiple trephines or via tamping through a distal cortical window.

Total hip arthroplasty in the underweight.

The outcomes of 20 patients diagnosed with osteoarthritis or rheumatoid arthritis with body mass index less than 18.5 (considered underweight) who received total hip arthroplasty at a single institution were reviewed. Surgical complications in the first 30 days after surgery included 1 prolonged surgical site drainage and 3 posterior dislocations. Two patients experienced medical complications that included hematemesis, confusion, aspiration pneumonia, and death. Sixty-five percent of the patients received at least one blood transfusion. Harris hip scores improved from 35 to 81 (P < .05) at an average of 6.1 years (2-10.1 years) of follow-up. Total hip arthroplasty is effective in patients who are underweight; however, they appear to be at an increased risk of dislocation and blood transfusion.

Kinematics of the stiff total knee arthroplasty.

The kinematics of 10 total knee replacements with poor flexion (<90 degrees ) were compared with 11 replacements with good flexion (>110 degrees ) at a mean of 3 years from surgery using optical calibration with implant shape-matching techniques from radiographs taken in standing, early-lunge, and late-lunge positions. There were no significant differences between groups in anteroposterior translation of the medial and lateral femoral condyles or tibial rotation during standing and early lunge. Groups differed in amount of posterior translation of the femoral condyles during late lunge because of the poor-flexion group's inability to achieve the same amount of flexion as the good-flexion group. Poor flexion after total knee arthroplasty, we conclude, is not associated with abnormal kinematics in the setting of well-aligned, well-fixed implants.

Failure of constrained acetabular liner without metal ring disruption.

Constrained acetabular liners can fail leading to recurrent dislocation. Failure can occur at any of the five possible interfaces: bone-acetabular shell, acetabular shell-constrained liner insert, constrained liner insert-bipolar head, bipolar head- femoral head and femoral head-trunion. We report a patient who presented with dissociation of the cemented Osteonics acetabular constrained liner (Stryker-Howmedica-Osteonics, Rutherford, New Jersey). The failure interface was at the factory pre-assembled constrained liner insert-bipolar head without any locking ring failure; instead there was deformation of the constrained liner insert's polyethylene rim, which facilitated dissociation. To our knowledge, there are no previous reports of such a failure mode pertaining to this type of constrained liner. Constrained acetabular liners are indicated during primary or revision total hip arthroplasty for patients who are at high risk for dislocations or who have had recurrent dislocations. Failure rates (typically recurrent dislocation) range from 4% to 29% at mid-term follow-up. The first report on the Osteonics acetabular constrained liner was published in 1994. Failures have been reported previously to occur at surgically controllable interfaces, such as the acetabular shell from the bony surface and the constrained liner insert from the acetabular metal shell, and have been attributable to excessive constraint or improper technique. All dissociations pertaining to factory-preassembled component interfaces have been attributed to breakage of the locking ring. This article presents the first case of disengagement of the tripolar constrained liner without disruption of the locking ring.

Effects of fondaparinux on wound drainage after total hip and knee arthroplasty.

BACKGROUND: The purpose of this investigation was to determine the effects of fondaparinux on postoperative wound drainage, length of hospital stay (LOS) and rate of surgical site infection in total joint patients. METHODS: 117 patients undergoing total joint arthroplasty treated with fondaparinux for venous thromboembolism (VTE) prophylaxis were prospectively studied. RESULTS: The average time to a dry wound was 3.4 days, with an average LOS of 3.77 days. Perioperative complications included 2 cases each of superficial cellulitis, deep vein thrombosis, and pulmonary embolism; there were no cases of deep infection. Multi-variate analysis showed increased patient BMI increased LOS (p = 0.0169). CONCLUSION: Fondaparinux is an effective drug for VTE prophylaxis in total joint arthroplasty with wound drainage and LOS comparable to historical controls of enoxaparin, warfarin, and rivaroxaban.

Transcriptional activation of cartilage oligomeric matrix protein by Sox9, Sox5, and Sox6 transcription factors and CBP/p300 coactivators.

The gene for cartilage oligomeric matrix protein (COMP) encodes a noncollagenous matrix protein that is expressed predominantly in cartilage. COMP gene expression is deficient in the Sox9-null mouse, but the molecular mechanism remains unknown. We have previously delineated a 30-bp negative regulatory element (NRE) and a 51-bp positive regulatory element (PRE) in the regulatory region of the COMP gene. Subsequently we isolated LRF transcription repressor as an NRE-binding protein and established that LRF inhibits COMP gene expression via recruiting histone deacetylase 1 (HDAC1) to the COMP promoter. In this study we demonstrated that Sox9, an essential transcription factor of chondrogenesis, binds to the COMP promoter at the PRE in which 13 nucleotides (TGTTTACCTTGTG) are required for the binding of Sox9. Sox9 activates COMP gene expression and this activation is PRE-dependent. Sox9 is required for COMP gene expression during chondrogenesis, since repression of Sox9 expression using the small interfering RNA approach inhibited COMP gene expression. In addition, activation of COMP gene expression by Sox9 requires the participation of transcription factors Sox5 and Sox6 as well as the coactivators CBP and p300 histone acetylase. It appears that there exists a balance between LRF repressor and Sox9 activator in the control of COMP gene, since transactivation of COMP gene by Sox9 was abolished by the coexpression of LRF, and excess Sox9 overcame the LRF-mediated inhibition. This study provides the first evidence that Sox9 directly associates with COMP gene promoter and that mediation of COMP gene activation by Sox9 involves Sox5, Sox6, CBP, and p300 coactivators.

ADAMTS-7: a metalloproteinase that directly binds to and degrades cartilage oligomeric matrix protein.

Degradative fragments of cartilage oligomeric matrix protein (COMP) have been observed in arthritic patients. The physiological enzyme(s) that degrade COMP, however, remain unknown. We performed a yeast two-hybrid screen (Y2H) to search for proteins that associate with COMP to identify an interaction partner that might degrade it. One screen using the epidermal growth factor (EGF) domain of COMP as bait led to the discovery of ADAMTS-7. Rat ADAMTS-7 is composed of 1595 amino acids, and this protein exhibits higher expression in the musculoskeletal tissues. COMP binds directly to ADAMTS-7 in vitro and in native articular cartilage. ADAMTS-7 selectively interacts with the EGF repeat domain but not with the other three functional domains of COMP, whereas the four C-terminal TSP motifs of ADAMTS-7 are required and sufficient for association with COMP. The recombinant catalytic domain and intact ADAMTS-7 are capable of digesting COMP in vitro. The enzymatic activity of ADAMTS-7 requires the presence of Zn2+ and appropriate pH (7.5-9.5), and the concentration of ADAMTS-7 in cartilage and synovium of patients with rheumatoid arthritis is significantly increased as compared to normal cartilage and synovium. ADAMTS-7 is the first metalloproteinase found to bind directly to and degrade COMP.

Factors associated with prolonged wound drainage after primary total hip and knee arthroplasty.

BACKGROUND: Prolonged wound drainage following total hip or total knee arthroplasty has been associated with an increased risk of postoperative morbidity. The purpose of this study was to determine the pharmacologic, surgical, and patient-specific factors that are associated with prolonged wound drainage and the relationship of this complication to the length of hospital stay and the rate of wound infections. METHODS: We conducted a retrospective observational study of 1211 primary total hip arthroplasties and 1226 primary total knee arthroplasties. Prospectively collected data included body mass index, intraoperative blood loss, surgical time, type of prophylaxis against deep venous thrombosis, and length of hospital stay. The association of these factors with the duration of postoperative wound drainage was analyzed. An acute infection developed after fifteen primary total hip arthroplasties and ten primary total knee arthroplasties. The patients with an acute postoperative infection were compared with their uninfected counterparts, and an odds ratio was determined to estimate the risk of prolonged wound drainage resulting in a wound infection. RESULTS: Morbid obesity was strongly associated with prolonged wound drainage in the total hip arthroplasty group (p = 0.001) but not in the total knee arthroplasty group (p = 0.590). An increased volume of drain output was an independent risk factor for prolonged wound drainage in both groups. Patients who received low-molecular-weight heparin for prophylaxis against deep venous thrombosis had a longer time until the postoperative wound was dry than did those treated with aspirin and mechanical foot compression or those who received Coumadin (warfarin); this difference was significant on the fifth postoperative day (p = 0.003) but not by the eighth postoperative day. Prolonged wound drainage resulted in a significantly longer hospital stay in both groups (p < 0.001). Each day of prolonged wound drainage increased the risk of wound infection by 42% following a total hip arthroplasty and by 29% following a total knee arthroplasty. CONCLUSIONS: Morbid obesity, the use of low-molecular-weight heparin, and a higher drain output were associated with a prolonged time until the postoperative wound was dry following a primary total hip arthroplasty, whereas a higher drain output was the only risk factor associated with prolonged drainage following a primary total knee arthroplasty. Prolonged drainage was associated with a higher rate of infection following a primary total hip arthroplasty, whereas obesity was the only identified independent risk factor for postoperative infection following a primary total knee arthroplasty.

Fixation systems of greater trochanteric osteotomies: biomechanical and clinical outcomes.

The development of cerclage systems for fixation of greater trochanteric osteotomies has progressed from monofilament wires to multifilament cables to cable grip and cable plate systems. Cerclage wires and cables have various clinical indications, including fixation for fractures and for trochanteric osteotomy in hip arthroplasty. To achieve stable fixation and eventual union of the trochanteric osteotomy, the implant must counteract the destabilizing forces associated with pull of the peritrochanteric musculature. The material properties of cables and cable grip systems are superior to those of monofilament wires; however, potential complications with the use of cables include debris generation and third-body polyethylene wear. Nevertheless, the cable grip system provides the strongest fixation and results in lower rates of nonunion and trochanteric migration. Cable plate constructs show promise but require further clinical studies to validate their efficacy and safety.

Massive femoral osteolytic lesion secondary to disengagement of a total knee tibial locking pin: case report.

The Anatomic Modular Knee (AMK; Depuy, Warsaw, Ind) was one of the first designs to incorporate a modular locking mechanism for the tibial insert; fixation was secured using a screw-in tibial tray-locking pin. This case report describes a patient who presented with instability and worsening knee pain 15 years following a primary total knee arthroplasty using the AMK prosthesis. Radiographs and intraoperative assessment revealed proximal migration of the tibial tray-locking pin into the medial femoral condyle resulting in a large osteolytic defect.

Heparin-induced thrombocytopenia and thrombosis.

Heparin-induced thrombocytopenia (HIT) and heparin induced thrombocytopenia with thrombosis (HITT) ar rare complications associated with use of unfractionate heparin (UFH) or low-molecular-weight heparin (LMWH) HIT is a benign clinical condition characterized by a mil drop in platelet count with no clinical significance. HIT is an immune-mediated reaction associated with a wide spread "hypercoagulable" state resulting in arterial an venous thrombosis. There is a higher incidence of HIT with UFH use than with LMWH use. Orthopedic surger patients are at higher risk for developing HITT than are patients who receive prophylactic heparin for cardiovascular surgery or medical reasons. Therapy for patients suspected of having HITT should begin with immedi ate discontinuation of heparin in any form followed by pharmacologic inhibition with thrombin (e.g., recombinant hirudin [lepirudin], argatroban, danaparoid sodium).

Regional gene therapy for full-thickness articular cartilage lesions using naked DNA with a collagen matrix.

A novel gene therapy approach for treating damaged cartilage is proposed that involves placing endotoxin-free cDNA containing the gene for bone morphogenetic protein-2 (BMP-2) in type I collagen sponges and then transferring the naked plasmid DNA construct to the injury site. A full-thickness cartilaginous defect in rabbits implanted with plasmid containing a marker gene (beta-galactosidase) showed expressed protein as detected by immunostaining. At 1 week postimplantation, mesenchymal cells subjacent to the defect had incorporated the implanted naked plasmid DNA and, once transfected, served as local bioreactors, transiently producing the gene product. Plasmids containing the gene for BMP-2 implanted in collagen sponges in cartilage lesions stimulated hyalinelike articular cartilage repair at 12 weeks postimplantation, nearly equivalent in quality to that induced by collagen sponges with recombinant BMP-2 protein. Our approach circumvents the risks of inflammation and immunogenic response associated with the use of viral vectors. Naked plasmid DNA as a vehicle for transferring therapeutic genes has been shown to be effective in a therapeutic model within rabbit articular cartilage and appears to be safe and cost effective.

Antibiotic susceptibility of bacteria infecting total joint arthroplasty sites.

BACKGROUND: Currently, there is no consensus regarding the principles of empiric antibiotic treatment of suspected periprosthetic infection following total knee and hip arthroplasties. This study was undertaken to attempt to establish such principles. METHODS: We performed a retrospective analysis of 146 patients who had had a total of 194 positive cultures of specimens obtained at the time of a reoperation following a total knee or total hip arthroplasty at one of two institutions. Patient demographic data, comorbid conditions, bacterial species, the antibiotic sensitivity profile, and the postoperative day on which the culture tested positive were recorded. RESULTS: Specimens from 110 hips and eighty-four knees were positive on culture. Seventy percent of the infections were classified as chronic; 17%, as acute postoperative; and 13%, as acute hematogenous. The mean time between the operation and the positive culture results was three days. Gram-positive organisms caused the majority of the infections. In the series as a whole, 88% of the bacteria were sensitive to gentamicin; 96%, to vancomycin; and 61%, to cefazolin. The most antibiotic-resistant bacterial strains were from patients for whom prior antibiotic treatment had failed. Acute postoperative infections had a greater resistance profile than did chronic or hematogenous infections. Bacteria isolated from patients with a hematogenous infection had a high sensitivity to both cefazolin and gentamicin. CONCLUSIONS: Empiric antibiotic treatment for suspected periprosthetic infection should be guided by the class of the infection and the findings of Gram staining. We believe that, until the final culture results are available, acute hematogenous infections should initially be treated by a combination of cefazolin and gentamicin therapy. All chronic and acute postoperative infections with Gram-positive bacteria and all cases in which a Gram stain fails to identify bacteria should be managed with vancomycin. Infections with Gram-negative bacteria should be managed with a third or fourth-generation cephalosporin. Infections with mixed Gram-positive and Gram-negative bacteria should be managed with a combination of vancomycin and a third or fourth-generation cephalosporin. Furthermore, we believe that if culture results and other confirmatory tests are not positive by the fourth postoperative day, termination of empiric antibiotic therapy should be considered.

Orthopedic surgical management of hip and knee involvement in patients with juvenile rheumatoid arthritis.

Juvenile rheumatoid arthritis is the most common arthritic disease of childhood and a leading cause of childhood disability, affecting an estimated 300,000 US children and adolescents aged < or =16 years. Approximately 10% to 30% of patients experience functional deficits resulting from both the articular and systemic manifestations of their disease, including leg length inequality and deformity, that are often more crippling than joint destruction. Surgical intervention to treat bone and soft-tissue deformity, leg length inequality, and joint destruction is indicated when medical therapy has failed. Synovectomy, soft-tissue release, osteotomy, and epiphysiodesis are used to treat deformity and early joint destruction. Arthroplasty remains the primary therapy for joint destruction, although it is fraught with complications specific to this young patient population.

Nonsurgical complications after total hip and knee arthroplasty.

Postoperative medical complications after total hip arthroplasty (THA) and total knee arthroplasty (TKA) may occur in patients of any age. However, percentage of adverse events increases with increasing patient age and can cause significant morbidity and even mortality. It is important that the orthopedist identify risk factors and symptoms and be knowledgeable in the treatment of nonsurgical postoperative complications. Nonsurgical complications after THA and TKA include pulmonary embolism, fat embolism syndrome, pneumonia, myocardial infarction, postoperative delirium, cerebrovascular accident, urinary retention, urinary tract infections, and deep vein thrombosis.

Multidisciplinary management of orthopedic patients with sickle cell disease.

With pharmacological treatment, the lifespan of the patient with sickle cell disease can be extended to the sixth decade. Currently the only curative therapy for sickle cell disease is hemopoietic cell transplantation, which is still undergoing technical refinement. Most patients can be expected to undergo at least one orthopedic surgical procedure in their lifetime. Multidisciplinary management of orthopedic patients with sickle cell disease will decrease the overall complication rates and improve clinical outcomes.