Prevention of venous thromboembolic disease following primary total knee arthroplasty. A randomized, multicenter, open-label, parallel-group comparison of enoxaparin and warfarin.

BACKGROUND: Patients treated with total knee arthroplasty are at high risk for the development of venous thromboembolism postoperatively. This study compared the efficacy and safety of two common thromboprophylactic agents, enoxaparin (a low-molecular-weight heparin) and warfarin. METHODS: Three hundred and forty-nine patients were included in a prospective, randomized, multicenter, open-label, parallel-group clinical trial. Treatment with enoxaparin (30 mg, administered subcutaneously twice daily) or warfarin (adjusted to an international normalized ratio of 2 to 3) was initiated during the immediate postoperative period, within eight hours after the surgery, and was continued for four to fourteen days. Venous thromboembolism was defined as deep-vein thrombosis documented by contrast venography, symptomatic deep-vein thrombosis documented by lower-extremity ultrasonography, or symptomatic pulmonary embolism confirmed by a positive lung scan or pulmonary angiography. RESULTS: In the all-treated-patients group, eighty (45%) of the 176 warfarin-treated patients had venous thromboembolism: fifty-nine (34%) had distal deep-vein thrombosis; twenty (11%), proximal deep-vein thrombosis; and one (0.6%), pulmonary embolism. Venous thromboembolism developed in significantly fewer (p = 0.0001) enoxaparin-treated patients (forty-four of 173; 25%): forty-one (24%) had distal deep-vein thrombosis, three (2%) had proximal deep-vein thrombosis, and none had pulmonary embolism. The enoxaparin-treated patients also had a significantly lower prevalence of proximal deep-vein thrombosis (p = 0.002). The estimated odds for the development of venous thromboembolism were 2.52 times greater (95% confidence interval, 2.00 to 3.19) with warfarin than they were with enoxaparin. Major hemorrhage occurred in four warfarin-treated patients and nine enoxaparin-treated patients; with the numbers available, this difference was not significant (p = 0.17). Clinically important operative-site hemorrhage occurred in six (3%) of the warfarin-treated patients and twelve (7%) of the enoxaparin-treated patients (p = 0.15). CONCLUSIONS: A fixed 30-mg subcutaneous dose of enoxaparin, administered twice daily, with the first dose administered within eight hours after the completion of surgery, was significantly more effective than adjusted-dose warfarin in reducing the occurrence of asymptomatic venous thromboembolism, including proximal deep-vein thrombosis, in patients undergoing total knee arthroplasty. With the numbers available, there was no significant difference between groups with regard to the occurrence of major hemorrhagic complications; however, the rate of overall hemorrhagic complications was higher in the enoxaparin group.

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.

The promising role of 18F-FDG PET in detecting infected lower limb prosthesis implants.

UNLABELLED: The purpose of this study was to evaluate the feasibility of using 18F-FDG and PET for the detection of infection associated with lower limb arthroplasty. METHODS: Seventy-four prostheses in 62 patients in whom infection was suspected after artificial hip or knee placement were studied with this technique. Images were obtained 60 min after an intravenous injection of FDG. The images were interpreted as positive for infection if tracer uptake was increased at the bone-prosthesis interface. A final diagnosis was made by surgical exploration or clinical follow-up for 1 y. PET results were compared with the follow-up outcome in all patients. RESULTS: The sensitivity, specificity, and accuracy of PET for detecting infection associated with knee prostheses were 90.9%, 72.0%, and 77.8%, respectively. The sensitivity, specificity, and accuracy of PET for detecting infection associated with hip prostheses were 90%, 89.3%, and 89.5%, respectively. Overall, the sensitivity was 90.5% and the specificity was 81.1% for detection of lower limb infections. CONCLUSION: FDG PET is a useful imaging modality for detecting infections associated with lower limb arthroplasty and is more accurate for detecting infections associated with hip prostheses than for detecting infections associated with knee prostheses.

Anatomy, histologic features, and vascularity of the adult acetabular labrum.

Acetabular labrum tears have been implicated as a cause of hip pain in adult patients. Few studies describe the anatomy, histologic features, and microvasculature of the acetabular labrum and labral tears. Fifty-five embalmed and 12 fresh-frozen adult hips with a mean age of 78 years (range, 61-98 years) were studied. Of these, 96 % (53 of 55) of the hips had labral tears, with 74% of the tears located in the anterosuperior quadrant. Histologically, the fibrocartilaginous labrum was contiguous with the acetabular articular cartilage through a 1- to 2-mm zone of transition. A consistent projection of bone extends from the bony acetabulum into the substance of the labrum that is attached via a zone of calcified cartilage with a well-defined tidemark. Two distinct types of tears of the labrum were identified histologically. The first consisted of a detachment of the fibrocartilaginous labrum from the articular hyaline cartilage at the transition zone. The second consisted of one or more cleavage planes of variable depth within the substance of the labrum. Both types of labral tears were associated with increased microvessel formation seen within the tear. The acetabular labrum tear appears to be an acquired condition that is highly prevalent in aging adult hips. Labral tears occur early in the arthritic process of the hip and may be one of the causes of degenerative hip disease.

Contribution of acetabular labrum to articulating surface area and femoral head coverage in adult hip joints: an anatomic study in cadavera.

The purpose of our study was to describe the gross anatomy of the adult acetabular labrum and to determine its contribution to the depth, surface area, and volume of the acetabulum. Fifty-five embalmed hips were studied. Each hip was disarticulated, and standardized measurements were taken. Calculations of the acetabular articulating surface area and volume, with and without the labrum, were performed based on these measurements. Average width of the acetabular labrum was 5.3 mm (SD, 2.6 mm). The labrum was wider anteriorly and superiorly than posteriorly. The surface area of the acetabulum without the labrum was 28.8 cm2; with the labrum, it was 36.8 cm2 (P < .0001). The volume of the acetabulum without the labrum was 31.5 cm3; with the labrum, it was 41.1 cm3 (P < .0001). There was no side-to-side difference in contribution of the labrum to either surface area or volume between right and left hips. Comparison of these indices for males and females showed statistically significant differences in absolute but not relative increases.

Cutaneous angiosarcoma in an irradiated breast after breast conservation therapy for cancer: association with chronic breast lymphedema.

The authors report a rare case of cutaneous angiosarcoma arising more than 5 years after excision of a 1.5 cm invasive ductal cancer of the breast. All lymph nodes were negative for metastatic breast cancer in this 68-year-old female. The patient had postoperative therapy consisting of 5040 cGy over a 5 week period using a 6 Megavolt linear accelerator. After radiation therapy to the breast and axillae, the patient developed chronic hard, taut edema of the irradiated right breast. Tamoxifen was administered for 5 years and then stopped. Three months after the cessation of tamoxifen, cutaneous angiosarcoma was found by skin biopsy. A complete mastectomy removed all tumor with clear margins. There are less than 60 cases of radiation associated breast angiosarcoma found in the literature. The presence of chronic lymphedema in the breast after radiation therapy possibly contributes to the development and is an early warning sign for later development of secondary angiosarcoma. The characteristic purple nodules and discoloration of the irradiated skin is the hallmark to suspect the diagnosis. The authors recommend long-term clinical surveillance for this tumor for all patients who have received breast conservative surgical therapy with concomitant radiation therapy for primary breast cancer.

A meta-analysis of thromboembolic prophylaxis following elective total hip arthroplasty.

BACKGROUND: Although several agents have been shown to reduce the risk of thromboembolic disease, there is no clear preference for thromboembolic prophylaxis in elective total hip arthroplasty. The purpose of this study was to define the efficacy and safety of the agents that are currently used for prophylaxis against deep venous thrombosis -- namely, low-molecular-weight heparin, warfarin, aspirin, low-dose heparin, and pneumatic compression. METHODS: A Medline search identified all randomized, controlled trials, published from January 1966 to May 1998, that compared the use of one of the prophylactic agents with the use of any other agent or a placebo in patients undergoing elective total hip arthroplasty. For a study to be included in our analysis, bilateral venography had to have been performed to confirm the presence or absence of deep venous thrombosis. Fifty-two studies, in which 10,929 patients had been enrolled, met the inclusion criteria and were included in the analysis. The rates of distal, proximal, and total (distal and proximal) deep venous thrombosis; symptomatic and fatal pulmonary embolism; minor and major wound-bleeding complications; major non-wound bleeding complications; and total mortality were determined for each agent in each study. The absolute risk of each outcome was determined by dividing the number of events by the number of patients at risk. A general linear model with random effects was used to calculate the 95 percent confidence interval of risk. A crosstabs of study by outcome was performed to test homogeneity (ability to combine studies). The risk of each outcome was compared among agents and between each agent and the placebo. RESULTS: With prophylaxis, the risk of total (proximal and distal) deep venous thrombosis ranged from 17.7 percent (low-molecular-weight heparin) to 31.1 percent (low-dose heparin); the risk with prophylaxis with any agent was significantly lower than the risk with the placebo (48.5 percent) (p < 0.0001). The risk of proximal deep venous thrombosis was lowest with warfarin (6.3 percent) and low-molecular-weight heparin (7.7 percent), and again the risk with any prophylactic agent was significantly lower than the risk with the placebo (25.8 percent) (p < 0.0001). Compared with the risk with the placebo (1.51 percent), only warfarin (0.16 percent), pneumatic compression (0.26 percent), and low-molecular-weight heparin (0.36 percent) were associated with a significantly lower risk of symptomatic pulmonary embolism. There were no significant differences among agents with regard to the risk of fatal pulmonary embolism or of mortality with any cause. The risk of minor wound-bleeding was significantly higher with low-molecular-weight heparin (8.9 percent) and low-dose heparin (7.6 percent) than it was with the placebo (2.2 percent) (p < 0.05). Compared with the risk with the placebo (0.28 percent), only low-dose heparin was associated with a significantly higher risk of major wound-bleeding (2.56 percent) and total major bleeding (3.46 percent) (p < 0.0001). CONCLUSIONS: The best prophylactic agent in terms of both efficacy and safety was warfarin, followed by pneumatic compression, and the least effective and safe was low-dose heparin. Warfarin provided the lowest risk of both proximal deep venous thrombosis and symptomatic pulmonary embolism. However, there were no identifiable significant differences in the rates of fatal pulmonary embolism or death among the agents. Significant risks of minor and major bleeding complications were observed with greater frequency with certain prophylactic agents, particularly low-molecular-weight heparin (minor bleeding) and low-dose heparin (both major and minor bleeding).

Insidious destruction of the hip by Mycobacterium tuberculosis and why early diagnosis is critical.

Tuberculosis has re-emerged as an important problem in the United States. More than 10 million people presently are infected with Mycobacterium tuberculosis in the United States alone. The symptoms at first presentation of the disease have become more diverse. With extrapulmonary manifestations, such as musculoskeletal infections, as the sole presenting sign, it often can be difficult to determine the correct diagnosis early in the course of the disease. The presenting symptoms, physical signs, and radiographic findings of intra-articular tuberculosis can mimic those of other intra-articular diseases, such as rheumatoid arthritis, osteoarthritis, and avascular necrosis. In view of the nonspecific findings early in course of the disease, tubercular infection should be considered in the differential diagnosis when there is insidious articular destruction. Failure to consider tuberculosis can lead to devastating outcomes otherwise preventable with today's chemotherapies.

Unusual case of septic arthritis of the hip: spread from adjacent adductor pyomyositis.

Distinguishing intracapsular and extracapsular hip infections may be clinically difficult. Because of this difficulty in diagnosis, the spread of an extracapsular infection into the hip joint may be missed and lead to significant joint destruction. The case of a patient who suffered from the spread of adductor pyomyositis to the hip joint is reported. The delay in diagnosis of an intracapsular hip infection led to significant intra-articular destruction and ultimately necessitated a Girdlestone resection arthroplasty. The patient's hip function was salvaged with a total hip arthroplasty. The presence of an extracapsular hip infection should mandate serial physical examinations and aggressive evaluation to rule out intracapsular spread. A delay in diagnosis of an intracapsular hip infection can lead to catastrophic results.

Experimental acute hematogenous osteomyelitis in mice. I. Histopathological and immunological findings.

This study investigated immunological responses to Staphylococcus aureus bone infection. Because considerable immunological information is available on the mouse, a murine model of acute hematogenous osteomyelitis was established. Osteomyelitis was created in the proximal tibia of C3H/HeJ mice by a tibial epiphyseal fracture followed by intravenous bacterial inoculation with Staphylococcus aureus (strain LS-1). Swelling and warmth of the limb was found, and following limb exposure, abscess formation was evident in the proximal tibia. Histological examination revealed distortion primarily at the hypertrophic zone of the physis and polymorphonuclear leukocyte infiltration throughout the damaged area of the proximal tibia. Local infection was demonstrated at the fracture site, evidenced by the recovery of Staphylococcus aureus following microbiological analysis of tissue specimens. Polymerase chain reaction was utilized to detect 16S ribosomal prokaryotic nucleic acid to demonstrate that the diagnosis of osteomyelitis could be established in the absence of conventional microbiological techniques. The infected mice had an increase of circulating large leukocytes (granulocytes) and an elevation of total serum immunoglobulin. Flow cytometry revealed significant increases in splenic B lymphocytes and in lymph-node CD4+ T lymphocytes. These results indicate that an experimental model of acute hematogenous osteomyelitis that closely resembles the pathology of the disease in humans may be consistently induced in mice. Furthermore, marked immunological changes may be observed in response to the Staphylococcus aureus bone infection.

Experimental acute hematogenous osteomyelitis in mice. II. Influence of Staphylococcus aureus infection on T-cell immunity.

A murine model of acute hematogenous osteomyelitis was used to study the immune response following Staphylococcus aureus infection and to examine the hypothesis that the bacteria may modify T-cell responses due to the production of bacterial enterotoxins with mitogenic or superantigenic activity. Lymph-node T cell-receptor expression was assessed with use of flow cytometry and reverse transcription-polymerase chain reaction techniques, and increased apoptosis (programmed cell death) in T-cell subsets was monitored. The expression and levels of circulating cytokines and T-cell cytokines within tissues surrounding the damaged area of the proximal tibia were also investigated. Analysis of T-cell receptors in experimental osteomyelitis revealed two distinct patterns of T-cell evolution during the disease. Certain T-cell subsets (Vbeta2, Vbeta3, Vbeta9, and Vbeta10) were activated and expanded during the first 24 hours after infection; they reached maximum levels 6 days after infection, followed by a return to pre-infection levels. In contrast, other T-cell subsets (Vbeta11, Vbeta12, Vbeta13, Vbeta14, and Vbeta16) contracted during the first 24 hours after infection, followed by expansion to a maximum level 9 days after infection. Activation and proliferation of T-cell subsets (notably Vbeta14 T cells) was followed by apoptosis, suggesting that staphylococcal bone infection caused superantigenic-like effects on the mouse immune system. Analysis of cytokine responses in local tissue revealed that the T-cell cytokines interleukin-2 and interferon-gamma showed a late and relatively short activation pattern compared with the inflammatory cytokines interleukin-1, interleukin-6, and tumor necrosis factor-alpha. The results suggest that Staphylococcus aureus bone infection may undermine the antibacterial immune response through downregulation of T-cell immunity and immune-cytokine production, which could increase the severity of the systemic infection and local osseous destruction that occur with acute hematogenous osteomyelitis.

Proteins bound to polyethylene components in patients who have aseptic loosening after total joint arthroplasty. A preliminary report.

BACKGROUND: Immunological responses to proteins that adhere to ultra-high molecular weight polyethylene have not, to our knowledge, been examined previously in patients who have aseptic loosening. In the current study, polyethylene components from forty-nine failed prostheses recovered during revision procedures were examined for the presence of antibodies that were bound to the polyethylene surface or that were reactive with other proteins that were bound to the polyethylene surface. METHODS: The polyethylene components consisted of thirty acetabular cups recovered during revision total hip arthroplasties and nineteen tibial components recovered during revision total knee arthroplasties. After extensive washing, bound proteins were extracted from the polyethylene components with use of 0.1-molar glycine-hydrogen chloride solution followed by four-molar guanidine hydrochloride solution. RESULTS: Sufficient protein for analysis was recovered from forty-two polyethylene components. Polyacrylamide gel electrophoresis demonstrated a minimum of one and a maximum of twelve protein bands, with molecular weights ranging from thirteen to 231 kilodaltons. Immunoblotting revealed the presence of type-I collagen in most (thirty-four) of the forty-two explants, whereas aggrecan proteoglycans were detected in eight samples. Immunoglobulin also was detected in most (thirty-three) extracts, whereas type-II collagen was consistently absent. The presence of autologous antibodies directed against polyethylene-bound proteins in sera drawn at the time of the revision was investigated. Antibodies that were reactive against the ultra-high molecular weight polyethylene-bound proteins were detected in twenty-six of the forty-two patients with use of the Western blot technique. The number of reactive bands ranged from one to six, and the strongest binding was directed against a 103-kilodalton protein. Assays for specificity revealed that these sera autologous antibodies were reactive against the type-I collagen that was present in the explant solutions. CONCLUSIONS: We hypothesize that immunoglobulin complexed with polyethylene may fix complement and that the complement cascade may in turn attract inflammatory cells to the polyethylene surface. Our data support the hypothesis that an immunological response to antigens bound to the polyethylene surface may contribute to aseptic loosening. CLINICAL RELEVANCE: Despite improvements in materials and designs of prostheses, aseptic loosening is the most common complication of total joint replacement, frequently leading to revision operations. We examined the immunological response to proteins that bind to ultra-high molecular weight polyethylene in patients who had aseptic loosening and discovered a high prevalence of antibodies to polyethylene-bound proteins. This immunological response may contribute to an inflammatory reaction in the periprosthetic tissue, ultimately leading to increased bone resorption around the prosthesis.

Predictors of injury among adult recreational in-line skaters: a multicity study.

OBJECTIVES: This study examined risk factors for injury, injury prevalence, safety gear use, and skating habits of adult recreational in-line skaters. METHODS: Randomly selected in-line skaters in 6 major US cities were interviewed. RESULTS: Only 6% of skaters consistently wore all 4 recommended types of safety gear. Skaters with greater skating experience were more likely to perform tricks, wear less safety gear, and sustain an injury. CONCLUSION: More experienced adult recreational in-line skaters are at increased risk for injury. Safety gear use in alarmingly low in adult recreational in-line skaters, especially experienced skaters. Safe skating education programs should consider targeting this newly recognized at-risk skating population.

The relationship between loading conditions and fracture patterns of the proximal femur.

In an attempt to test the hypothesis of spontaneous hip fracture, seven pairs of femurs, with ages ranging from 59 to 90, were tested under two loading conditions designed to simulate muscular contraction. Simulated iliopsoas contraction produced femoral neck fractures at an average normalized ultimate load of 5.2 +/- 0.8 times body weight. Simulated gluteus medius contraction produced sub-/inter-trochanteric fractures at an average normalized ultimate load of 4.1 +/- 0.6 times body weight. The average ultimate load for all specimens was 3040 +/- 720 N. Fracture patterns produced by both loading conditions were clinically relevant. The results from this study suggest that abnormal contraction produced by major rotator muscles could induce hip fracture.