Comparison of ximelagatran, an oral direct thrombin inhibitor, with enoxaparin for the prevention of venous thromboembolism following total hip replacement. A randomized, double-blind study.

BACKGROUND: Prophylaxis is recommended following total joint replacement because of the high risk of venous thromboembolism (VTE). Postoperative low-molecular-weight heparin (LMWH) reduces the incidence of venographically detected deep vein thrombosis (DVT) to about 10-15% in total hip replacement (THR) patients. Ximelagatran is a novel, oral direct thrombin inhibitor that selectively and competitively inhibits both free and clot-bound thrombin. We compared the efficacy and safety of ximelagatran with those of enoxaparin for the prevention of VTE in patients undergoing THR. METHODS: This was a prospective, randomized, multicenter, double-blind study conducted principally in the USA and Canada. Patients received fixed-dose oral ximelagatran 24 mg bid or subcutaneous enoxaparin 30 mg bid and matched placebo for 7-12 days; both regimens were initiated the morning after surgery. The incidence of VTE (by postoperative day 12) included thrombosis determined by mandatory venography of the leg on which surgery was performed and symptomatic, objectively proven DVT or pulmonary embolism (PE). VTE and bleeding events were interpreted by an independent central adjudication committee for primary analysis. RESULTS: Of the 1838 patients randomized, 1557 had either adequate venography or symptomatic, proven VTE (efficacy population). Overall rate of venography acceptable for evaluation was 85.4%. Overall rates of total VTE were 7.9% (62 of 782 patients) in the ximelagatran group and 4.6% (36 of 775 patients) in the enoxaparin group, with an absolute difference of 3.3% and a 95% confidence interval for the difference of 0.9% to 5.7%. Proximal DVT and/or PE occurred in 3.6% (28 of 782 patients) in the ximelagatran group and 1.2% (nine of 774 patients) in the enoxaparin group. Major bleeding events were observed in 0.8% (seven of 906) of the ximelagatran-treated patients and in 0.9% (eight of 910) of the enoxaparin-treated patients (P > 0.95). Non-inferiority of ximelagatran 24 mg bid based on a prespecified margin of 5% was not met, resulting in superiority of the enoxaparin regimen. CONCLUSIONS: Both ximelagatran and enoxaparin decreased the overall rate of VTE compared with that reported historically. However, in this study, enoxaparin 30 mg bid was more effective than ximelagatran 24 mg bid for prevention of VTE in THR. Oral ximelagatran was used without coagulation monitoring, was well tolerated, and had bleeding rates comparable to those of enoxaparin. Further refinement by testing a higher dose of ximelagatran in the patients undergoing THR is warranted.

Role of knee aspiration after resection of the infected total knee arthroplasty.

Recognizing persistent infection after resection arthroplasty and implantation of cement spacers in the infected total knee arthroplasty is often difficult. The purpose of this study was to determine whether aspiration of the knee after resection arthroplasty is valuable for determining the presence of ongoing infection. Thirty-four previously infected knees that were aspirated and cultured after resection arthroplasty, implantation of cement spacers, and intravenous antibiotics for an average of 6.3 weeks were identified. There were 8 cases of persistent infection-none identified on preoperative aspiration. Two preoperative cultures were false positive for Staphylococcus epidermidis. Preoperative cultures were negative in 32 knees, with 8 false-negative results. The antibiotic-free interval among all cases averaged 20 days; the cases with false-negative results from aspiration had an antibiotic-free interval averaging 11.5 days, compared with an average of 26 days among all other cases. Aspiration of knees after resection arthroplasty had sensitivity of 0%, positive predictive value of 0%, and accuracy of 71%. Specificity was 92%, and negative predictive value was 75%. A negative result from joint aspiration after resection arthroplasty does not necessarily rule out the presence of ongoing infection. False-negative results may be observed if joint aspiration is not delayed more than 2 to 3 weeks.

Tibial osteonecrosis.

Spontaneous osteonecrosis of the tibial plateau involves a continuum of change observed in the subchondral zone that is commonly associated with early and mid stages of osteoarthritis. The typical patient is an elderly woman who experiences a sudden onset of pain in the medial aspect of the knee. The diagnosis of this under-appreciated clinical entity may be difficult, but careful examination and judicious use of imaging studies, as well as a high index of suspicion, may facilitate the accurate diagnosis. Although the radiographs may initially be normal (with the exception of mild arthrosis), radionuclide scans and MRI can be of great value. The MRI studies usually show a decreased signal intensity on a T1-weighted image, but may be normal in the early course of the disease. The T2-weighted images and fat suppression views are helpful in establishing a diagnosis and determining the extent of involvement. Recognition of this problem may help to avoid unnecessary intra-articular surgery. Many of these patients have complete or partial resolution of symptoms by 1 year, after a period of protected weight bearing. Nonetheless, surgery may be necessary for more advanced lesions and in those patients with progressive arthrosis.

Treatment of osteonecrosis of the knee.

There are several options for the treatment of patients with osteonecrosis about the knee. Three appear to be the most effective and include conservative treatment for small lesions without evidence of structural collapse, core decompression for relief of pain and possible delay in structural collapse in the patients with steroid-induced osteonecrosis, and either unicompartmental or total knee arthroplasty. Although other modalities have been reported, these three remain the most widely reported and generally offer the greatest success. With better recognition of these problems, longer duration follow-up, and larger patient series, the answers to the best treatment regimen will become better defined.

Determining femoral rotational alignment in total knee arthroplasty: reliability of techniques.

Several anatomic axes routinely are used for determining femoral rotational alignment in total knee arthroplasty. The purpose of this study was to determine the reliability of these techniques. The transepicondylar axis, anteroposterior axis, and balanced flexion gap tension line were identified relative to the posterior condylar axis in 8 fresh frozen cadaver knees by 3 independent observers. The flexion-extension axis was defined in each knee for comparison. The anteroposterior and balanced tension axes defined most reliably the flexion-extension axis and best balanced the flexion gap with no significant interobserver differences. The transepicondylar axis was less predictable and significantly more externally rotated than the anteroposterior axis (P < .005) and the balanced tension line (P < .00001). Flexion gap tensioning may offer superior reliability because of its independence of obscured or distorted bone landmarks.

A meta-analysis of thromboembolic prophylaxis in total knee arthroplasty.

Deep venous thrombosis (DVT) is common in total knee arthroplasty (TKA). Because of the rarity of the most serious outcomes, most randomized controlled trials lack the power to analyze these outcomes. A meta-analysis was performed for agents used in DVT prophylaxis in TKA employing a Medline literature search. Study inclusion criteria were randomized controlled trials comparing prophylactic agents in elective TKA with mandatory screening for DVT by venography. Fourteen studies (3,482 patients) met inclusion criteria. For total DVT, all agents except dextran and aspirin protected significantly better than placebo (P < .0001). For proximal DVT rates, low-molecular-weight heparin was significantly better than warfarin (P = .0002). There was a trend that aspirin was better than warfarin (P = .0106). No significant difference was found for symptomatic pulmonary embolism, fatal pulmonary embolism, major hemorrhage, or total mortality.

Changes in bone density after cemented total knee arthroplasty: influence of stem design.

Total knee arthroplasty has shown excellent survivorship in short-term and intermediate-term studies. With longer follow-up, however, aseptic loosening becomes an increasing cause of failure. Dual-energy x-ray absorptiometry scanning has shown that stress shielding occurs from altered mechanical loading. The purpose of this study is to determine if tibial stem design affects bone density in the longterm. Bone densities in the proximal tibia with and without cemented stems were compared at an average of 94 months after surgery. The bone quality under the Miller-Galante I prosthesis, which has 4 0.5-cm pegs, was compared with the bone quality under a Press-Fit Condylar prosthesis with a single 4-cm stem. Each group was also compared with the unoperated contralateral tibia. Results showed that there is a significantly reduced density of bone in the tibial metaphysis in the cemented stemmed group but not in the pegged group. There were no changes distally in the diaphyseal bone. This study supports the contention that the use of a cemented stem reduces proximal stresses and may result in proximal bone resorption. Although the use of a stem provides excellent resistance to lift-off and shear, it comes at a price. The proximal resorption may contribute to the persistence of tibial component loosening as a primary threat to survivorship. This bone loss may complicate revision surgery. Consideration should be given to using shorter tibial stems, less cement, or alternative designs that avoid long-stem fixation.

Total knee arthroplasty in patients 40 years of age and younger with osteoarthritis.

The results of 32 total knee arthroplasties performed for osteoarthritis in 32 patients who were 40 years of age or younger are reviewed. At a mean followup of 7.9 years (minimum, 5 years), the Knee Society knee scores increased from an average of 47 to 88 points, and the function scores increased from 45 to 70 points. Overall, Knee Society knee scores were considered good or excellent in 82% of patients (26 knees) and fair or poor in 18% (six knees). Postoperative function scores were good or excellent in only 40% (13 knees). The average postoperative flexion arc was 110 degrees. If patients involved in worker's compensation cases are excluded from analysis, the results improved substantially, with range of motion averaging 113 degrees, and Knee Society knee scores and function scores averaging 92 points and 77 points, respectively. Excluding the five patients involved in workmen's compensation cases, knee scores were good or excellent in 91% of patients (25 knees) and function scores were good or excellent in 50% of patients (14 knees). Three revisions were performed for aseptic failure; one additional patient has radiographic evidence of tibial loosening, representing an aseptic failure rate of 12.5% at 8 years. Although slightly higher than observed in older patients, this failure rate still may be considered acceptable for this population of patients with severely affected knees who are not considered candidates for nonarthroplasty surgery. Despite a slightly higher tendency for aseptic failures in this group of patients, cemented total knee arthroplasty may provide some patients younger than 40 years of age with severe debilitating and recalcitrant osteoarthrosis, an important option with reasonable mid- and long-term results.

Cartilage-reactive T cells in rheumatoid synovium.

Rheumatoid arthritis (RA) is an inflammatory polyarthritis genetically linked to HLA-DR4 and related haplotypes. RA synovial tissue is characterized by T cell infiltration and activation of macrophage-like cells, strongly implicating a T cell-antigen-presenting cell (APC) interaction in RA pathogenesis. To investigate the nature of the antigens driving the T cell response, synovial tissue was obtained from a patient with chronic RA and T cells were enriched. These T cells were stimulated by endogenous APC from the same synovial tissue. The T cell lines were subsequently evaluated for responsiveness to autologous APC and cartilage antigens. Specific proliferative responses to autologous APC which were enhanced by cartilage extract were seen. Immunomagnetic bead selection and RT-PCR was used to identify TCR alphabeta pairs which appeared to respond to antigen(s) in the cartilage extract. T cell clones derived from the same joint were shown to release IL-2 in response to the cartilage extract and expressed a related TCR. With these experiments we have shown direct evidence that autoreactive T cells are found within the inflamed rheumatoid synovium and, further, that the antigens driving these T cells are cartilage derived. Since the antigens recognized by these populations of T cells are found within cartilage our data provides evidence that RA pathology could be related to a self-driven autoimmune response to cartilage proteins.

Simultaneous femoral osteotomy and total knee arthroplasty for treatment of osteoarthritis associated with severe extra-articular deformity.

BACKGROUND: In the presence of large extra-articular deformity, complex imbalance of the collateral ligaments may result if standard techniques of soft-tissue releases and intra-articular bone resection are used during total knee arthroplasty. The purpose of this paper is to review our experience with simultaneous corrective osteotomy and total knee arthroplasty for the treatment of severe extra-articular femoral deformity associated with ipsilateral osteoarthritis of the knee. METHODS: The results of simultaneous corrective osteotomy and total knee arthroplasty in eleven knees with osteoarthritis and associated extra-articular angular deformity of the femur were reviewed retrospectively. The femoral deformity resulted from fracture malunion in ten knees and from hypophosphatemic rickets in one. There were five primarily uniplanar deformities (four varus deformities and one antecurvatum deformity), five biplanar (varus and antecurvatum) deformities, and one triplanar (varus, antecurvatum, and internal rotation) deformity. Four knees were approached through a standard medial parapatellar arthrotomy and seven, through an anterolateral subvastus approach with an osteotomy of the tibial tubercle. The site of the femoral osteotomy was fixed with a blade-plate in seven patients, a press-fit long-stemmed femoral component in two, and a retrograde femoral nail in two. An extramedullary alignment system was utilized in eight patients, and intramedullary alignment was used in three. RESULTS: The duration of follow-up averaged forty-six months (range, twenty-six to eighty-eight months). According to the classification system of the Knee Society, the mean function score increased from 22 points preoperatively to 81 points at the time of follow-up and the mean knee score increased from 10 points preoperatively to 87 points at the time of follow-up. The mean flexion contracture decreased from 19 degrees preoperatively to 2 degrees at the time of follow-up. The arc of motion averaged 56 degrees (range, 30 to 75 degrees) preoperatively and 89 degrees (range, 65 to 115 degrees) at the time of follow-up. The mechanical alignment in the coronal plane was restored to within 2 degrees of normal in each patient. Ten femoral osteotomy sites healed, and one, in a patient treated with a press-fit long-stemmed femoral component, had not healed by the time of follow-up. All seven sites of the tibial tubercle osteotomies healed. There were no complete radiolucent lines at the prosthetic interfaces, and no total knee arthroplasty was revised. One patient had a nonfatal postoperative pulmonary embolism. As determined by clinical examination and the patients' assessment of function, no ligament imbalance was noted at the time of the most recent follow-up. CONCLUSIONS: Simultaneous femoral osteotomy and total knee arthroplasty is a technically difficult but effective treatment for patients with severe femoral deformity associated with ipsilateral osteoarthritis of the knee. We recommend that the femoral osteotomy site be secured with a plate or a locked intramedullary nail, depending on the location of the deformity and the subsequent osteotomy.

Subchondral magnetic resonance imaging changes in early osteoarthrosis associated with tibial osteonecrosis.

SUMMARY: The authors report on 41 patients with acute or subacute knee pain and early or midstage degenerative arthrosis with osteonecrotic lesions in the subchondral and metaphyseal region of the medial proximal tibia. Each lesion was identified only on magnetic resonance images (MRI). These MRI changes are classified and the clinical course is defined during a follow-up period averaging 4.5 years. Radiographically, 22 patients had minimal degenerative changes; 12 had moderate arthritis; and 7 were normal. With MRI, 3 distinct types of lesions were identified. Type A lesions had localized areas of decreased signal in the subchondral area. Type B lesions had diffuse signal changes with extension into the metaphysis. Type C lesions had metaphyseal involvement as well as a marginated serpentine subchondral rim usually associated with advanced osteonecrosis. There were 9 type A lesions, 23 type B, and 9 type C. At the end of 1 year, 33 patients (80%) had no or mild symptoms, and 8 (20%) had persistent moderate pain. At 4.5-year follow-up, most patients had symptoms consistent with progressive osteoarthrosis, 12 patients had severe symptoms (29%), 17 (41%) had mild or moderate symptoms, and only 12 (29%) were asymptomatic or had minimal symptoms. The type of MRI change seen initially was predictive of prognosis. Only 6 (19%) of the 32 patients with type A or B findings had severe symptoms at last follow-up. Six (66%) of the 9 patients with a type C MRI lesion had severe symptoms or had an operation by last follow-up. Twelve patients had follow-up MRI at a mean 15 months (range, 12 to 18 months) after the initial evaluation. The type A and B changes were either absent or significantly reduced. The type C subchondral marginated rim changes remained but metaphyseal involvement was reduced. There appears to be a spectrum of tibial subchondral MRI changes associated with sudden onset of medial knee pain in patients with early osteoarthritis of the knee. These changes may be indicative of osteonecrosis. The initial MRI classification is useful in predicting prognosis. Recognition of this problem may avoid unnecessary intra-articular surgery.

Total knee arthroplasty in patients 90 years of age and older.

With increasing longevity, more patients older than age 90 now are becoming candidates for total knee arthroplasty. This article reviews our experience with the perioperative morbidity and early outcomes in 12 patients older than age 90, undergoing 15 total knee surgeries. Postoperative Knee Society clinical and functional scores showed excellent outcomes, and the quality of life is enhanced. There were no significant surgical complications; however, there were several nonsurgical complications, including mental confusion (3), urinary retention (3), atrial fibrillation (2), atrial flutter (1), and gallstone retention and gastrointestinal bleed (1). Most of these complications stemmed directly from the preoperative medical condition. These are predictive and therefore may be recognized early and treated aggressively. Total knee surgery can be performed safely in patients older than 90 years old with excellent pain relief and enhanced quality of life. The surgeon should be aware of the patient's past medical history because this predisposes to postoperative morbidity.

Aseptic complications after total knee arthroplasty.

Aseptic complications after total knee arthroplasty are occurring less frequently than they did one or two decades ago. This is related in part to technical advancements, design improvements, and changes in perioperative management. Extensor mechanism dysfunction is the most frequent complication and the most commonly cited reason for secondary surgery after total knee arthroplasty. Mechanical wear, tibiofemoral instability, periprosthetic fracture, thromboembolic disease, compromised wound healing, neurovascular problems, and stiffness are less common, but nevertheless troublesome, sources of dysfunction after total knee arthroplasty. Complications compromise outcomes, and the most effective way of dealing with complications is prevention.

Predonated autologous blood transfusions after total knee arthroplasty: immediate versus delayed administration.

Efforts to avoid complications associated with transfusion of allogeneic blood have increased the use of preoperatively donated autologous blood (PAB). A major controversy has arisen: Should the same criteria be used for transfusion of autologous as allogeneic red cells? This study prospectively and randomly compared giving PAB immediately after total knee arthroplasty (TKA), beginning in the recovery room or delaying a transfusion until the patient's hemoglobin had fallen to less than a 9.0 g/dL transfusion trigger point. The results show that patients who received immediate transfusion had fewer nonsurgical complications (P < .002). Because TKAs are associated with an average blood loss of 1,400 mL, we recommend that PAB be used in the immediate postoperative period, especially in the elderly, in whom the risk for cardiac or nonsurgical complications is inherently increased.

Total knee arthroplasty for steroid-induced osteonecrosis.

There have been only a few reports that evaluate the outcome of total knee arthroplasty in patients with steroid-induced osteonecrosis of the knee. We retrospectively reviewed 31 total knee arthroplasties in 24 patients with confirmed steroid-induced osteonecrosis of the knee. The average follow-up was 64 months. Of surviving knees, 92% had significant improvement in knee scores. Five knees (16%) required a revision procedure. Reasons for revision were aseptic loosening in 3 knees and sepsis in 2 knees. Complications not requiring revision occurred in 6 of 31 knees (19%). Survivorship of total knee arthroplasty to revision in patients with steroid-induced avascular necrosis of the knee was 84% at 5 years. Although there was a slightly higher complication rate, this may, in part, be due to the severity of the patients' underlying disease processes. Total knee arthroplasty can be a successful procedure for chronically ill patients with steroid-induced osteonecrosis.

Nonoperatively treated displaced bimalleolar and trimalleolar fractures: a 20-year follow-up.

This study evaluates the long-term results of displaced bi- and trimalleolar fractures treated closed. Few reports exist in the literature regarding the long-term outcomes of ankle fractures, and none of these specifically addresses displaced bi- and trimalleolar fractures treated nonoperatively. This study analyzed the results of bi- and trimalleolar fractures treated by a single surgeon from 1973 to 1981. As was the standard of care at that time, these fractures were treated nonoperatively if a stable reduction was achieved and maintained. Serial radiographs confirmed the maintenance of reduction in a non-weightbearing long leg cast for 6 weeks and then a short leg walking cast for 6 weeks. Of the 34 patients in this series, 19 were available for review, 10 were deceased, and five were lost to follow-up. The average age at the time of injury was 39 years (range, 17-79 years), and the average length of follow-up was 20 years (range, 16-24 years). At the time of review, only two patients with trimalleolar fractures were minimally symptomatic or had radiographic evidence of mild degenerative changes. The average American Orthopaedic Foot and Ankle Score was 98 of 100 points (range, 87-100 points). This long-term follow-up shows that bi- and trimalleolar fractures can be treated nonoperatively if an anatomic reduction is maintained and closely followed. With reports indicating as much as a 5% deep infection rate and a 10% incidence of loss of reduction after internal fixation, universally recommending an operation for these injuries should be reconsidered, especially in high surgical risk patients.

The role of aspirin for thromboembolic disease in total joint arthroplasty.

Fatal PE is a real problem and cannot be minimized. However, it must be appropriately balanced to other perioperative risks. It appears that fatal PE, as reported in the recent literature, is the same no matter which chemoprophylactic agent is used, with a rate of approximately 0.1% to 0.2%. With the use of aspirin as chemoprophylaxis after TKA, we have demonstrated the risk of fatal PE to be 0.15%. Because of our experience, the current data in the literature, and the need to carefully balance risk, we continue to use aspirin as our prophylactic agent of choice.