Teemu Moilanen

Risk factors for infection after knee arthroplasty. A register-based analysis of 43,149 cases.

BACKGROUND Clinical studies have revealed a number of important risk factors for postoperative infection following total knee arthroplasty. Because of the small numbers of cases in those studies, there is a risk of obtaining false-negative results in statistical analyses. The purpose of the present study was to determine the risk factors for infection following primary and revision knee replacement in a large register-based series. METHODS A total of 43,149 primary and revision knee arthroplasties, registered in the Finnish Arthroplasty Register, were followed for a median of three years. The Finnish Arthroplasty Register and the Finnish Hospital Discharge Register were searched for surgical interventions that were performed for the treatment of deep postoperative infections. Cox regression analysis with any reoperation performed for the treatment of infection as the end point was performed to determine the risk factors for this adverse outcome. RESULTS Three hundred and eighty-seven reoperations were performed because of infection. Both partial and complete revision total knee arthroplasty increased the risk of infection as compared with the risk following primary knee replacement. Male patients, patients with seropositive rheumatoid arthritis or with a previous fracture around the knee, and patients with constrained and hinged prostheses had increased rates of infection after primary arthroplasty. Wound-related complications increased the risk of deep infection. The rate of septic failure was lower after unicondylar than after total condylar primary knee arthroplasty, but the difference was not significant. The combination of parenteral antibiotic prophylaxis and prosthetic fixation with antibiotic-impregnated cement protected against septic failure, especially after revision knee arthroplasty. Following revision total knee arthroplasty, diagnosis and prosthesis type had no effect, but previous revision for the treatment of infection and wound-healing problems predisposed to repeat revision for the treatment of infection. CONCLUSIONS There was an increased risk of deep postoperative infection in male patients and in patients with rheumatoid arthritis or a fracture around the knee as the underlying diagnosis for knee replacement. The results of the present study suggest that the infection rate is similar after partial revision and complete revision total knee arthroplasties. Combining intravenous antibiotic prophylaxis with antibiotic-impregnated cement seems advisable in revision arthroplasty.

Obesity, diabetes, and preoperative hyperglycemia as predictors of periprosthetic joint infection: a single-center analysis of 7181 primary hip and knee replacements for osteoarthritis.

BACKGROUND Diabetes and obesity are common in patients undergoing joint replacement. Studies analyzing the effects of diabetes and obesity on the occurrence of periprosthetic joint infection have yielded contradictory results, and the combined effects of these conditions are not known. METHODS The one-year incidence of periprosthetic joint infections was analyzed in a single-center series of 7181 primary hip and knee replacements (unilateral and simultaneous bilateral) performed between 2002 and 2008 to treat osteoarthritis. The data regarding periprosthetic joint infection (defined according to Centers for Disease Control and Prevention criteria) were collected from the hospital infection register and were based on prospective, active surveillance. Patients diagnosed with diabetes were identified from the registers of the Social Insurance Institution of Finland. The odds ratios (ORs) for infection and the accompanying 95% confidence intervals (CIs) were calculated with use of binary logistic regression with adjustment for age, sex, American Society of Anesthesiologists risk score, arthroplasty site, body mass index, and diabetic status. RESULTS Fifty-two periprosthetic joint infections occurred during the first postoperative year (0.72%; 95% CI, 0.55% to 0.95%). The infection rate increased from 0.37% (95% CI, 0.15% to 0.96%) in patients with a normal body mass index to 4.66% (95% CI, 2.47% to 8.62%) in the morbidly obese group (adjusted OR, 6.4; 95% CI, 1.7 to 24.6). Diabetes more than doubled the periprosthetic joint infection risk independent of obesity (adjusted OR, 2.3; 95% CI, 1.1 to 4.7). The infection rate was highest in morbidly obese patients with diabetes; this group contained fifty-one patients and periprosthetic infection developed in five (9.8%; 95% CI, 4.26% to 20.98%). In patients without a diagnosis of diabetes at the time of the surgery, there was a trend toward a higher infection rate in association with a preoperative glucose level of ≥6.9 mmol/L (124 mg/dL) compared with <6.9 mmol/L. The infection rate was 1.15% (95% CI, 0.56% to 2.35%) in the former group compared with 0.28% (95% CI, 0.15% to 0.53%) in the latter, and the adjusted OR was 3.3 (95% CI, 0.96 to 11.0). The type of diabetes medication was not associated with the infection rate. CONCLUSIONS Diabetes and morbid obesity increased the risk of periprosthetic joint infection following primary hip and knee replacement. The benefits of joint replacement should be carefully weighed against the incidence of postoperative infection, especially in morbidly obese patients. LEVEL OF EVIDENCE Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Leptin enhances synthesis of proinflammatory mediators in human osteoarthritic cartilage--mediator role of NO in leptin-induced PGE2, IL-6, and IL-8 production.

Obesity is an important risk factor for osteoarthritis (OA) in weight-bearing joints, but also in hand joints, pointing to an obesity-related metabolic factor that influences on the pathogenesis of OA. Leptin is an adipokine regulating energy balance, and it has recently been related also to arthritis and inflammation as a proinflammatory factor. In the present paper, the effects of leptin on human OA cartilage were studied. Leptin alone or in combination with IL-1 enhanced the expression of iNOS and COX-2, and production of NO, PGE2, IL-6, and IL-8. The results suggest that the effects of leptin are mediated through activation of transcription factor nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathway c-Jun NH2-terminal kinase (JNK). Interestingly, inhibition of leptin-induced NO production with a selective iNOS inhibitor 1400 W inhibited also the production of IL-6, IL-8, and PGE2, and this was reversed by exogenously added NO-donor SNAP, suggesting that the effects of leptin on IL-6, IL-8, and PGE2 production are dependent on NO. These findings support the idea of leptin as a factor enhancing the production of proinflammatory factors in OA cartilage and as an agent contributing to the obesity-associated increased risk for osteoarthritis.

Incidence of Prosthetic Joint Infections After Primary Knee Arthroplasty

We report the 1-year incidence of postoperative infections in an unselected series of 2647 consecutive primary knee arthroplasties (3137 knees) performed in a modern specialized hospital dedicated solely to joint arthroplasty surgery in 2002 to 2006. The rates of superficial and prosthetic joint infections were 2.9% and 0.80%, respectively. Prospective surveillance by hospital infection register failed to detect 6 of the 24 prosthetic joint infections. Increased rate of prosthetic joint infections was associated with complex surgery and with several patient-related factors, for example, comorbidity, obesity, and poor preoperative clinical state. The rate of prosthetic joint infections in contemporary knee arthroplasty is low and mainly related to patient-related factors, of which patient comorbidity has the most profound effect on the infection rate.

Younger age increases the risk of early prosthesis failure following primary total knee replacement for osteoarthritis. A follow-up study of 32,019 total knee replacements in the Finnish Arthroplasty Register.

Background and purpose Total knee replacements (TKRs) are being increasingly performed in patients aged ≤ 65 years who often have high physical demands. We investigated the relation between age of the patient and prosthesis survival following primary TKR using nationwide data collected from the Finnish Arthroplasty Register. Materials From Jan 1, 1997 through Dec 31, 2003, 32,019 TKRs for primary or secondary osteoarthritis were reported to the Finnish Arthroplasty Register. The TKRs were followed until the end of 2004. During the follow-up, 909 TKRs were revised, 205 (23%) due to infection and 704 for other reasons. Results Crude overall implant survival improved with increasing age between the ages of 40 and 80. The 5-year survival rates were 92% and 95% in patients aged ≤ 55 and 56–65 years, respectively, compared to 97% in patients who were > 65 years of age (p < 0.001). The difference was mainly attributable to reasons other than infections. Sex, diagnosis, type of TKR (condylar, constrained, or hinge), use of patellar component, and fixation method were also associated with higher revision rates. However, the differences in prosthesis survival between the age groups ≤ 55, 56–65, and > 65 years remained after adjustment for these factors (p < 0.001). Interpretation Young age impairs the prognosis of TKR and is associated with increased revision rates for non-infectious reasons. Diagnosis, sex, type of TKR, use of patellar component, and fixation method partly explain the differences, but the effects of physical activity, patient demands, and obesity on implant survival in younger patients warrant further research.

The effect of storage on the fatty acid composition of human serum

The composition of fatty acids in blood plasma gives a rough estimate of the quality of dietary fat. In epidemiological studies serum is often used instead of plasma and the samples are stored at various temperatures for different time periods before analysis. Since blood contains enzymes capable of esterifying and hydrolysing lipids, it is possible that fatty acids are transferred from one lipid fraction to another and thus the fatty acid composition of a given lipid fraction may change, e.g. when blood is allowed to clot at room temperature. During prolonged storage the polyunsaturated fatty acids may autooxidise. Because of insufficient information about the subject in the literature, the present study aimed at quantifying changes in serum fatty acid composition possibly taking place during clotting or storage. Fatty acids of cholesteryl esters (CE), triacylglycerols (TG), free fatty acids (FFA) and phospholipids (PL), were analysed by gas chromatography. Plasma samples served as controls: they were immediately cooled and analysed within an hour.

Adiponectin associates with markers of cartilage degradation in osteoarthritis and induces production of proinflammatory and catabolic factors through mitogen-activated protein kinase pathways

IntroductionAdiponectin is an adipokine that regulates energy metabolism and insulin sensitivity, but recent studies have pointed also to a role in inflammation and arthritis. The purpose of the present study was to investigate the association and effects of adiponectin on inflammation and cartilage destruction in osteoarthritis (OA).MethodsCartilage and blood samples were collected from 35 male OA patients undergoing total knee replacement surgery. Preoperative radiographs were evaluated using Ahlbäck classification criteria for knee OA. Circulating concentrations of adiponectin and biomarkers of OA, that is, cartilage oligomeric matrix protein (COMP) and matrix metalloproteinase 3 (MMP-3), were measured. Cartilage samples obtained at the time of surgery were cultured ex vivo, and the levels of adiponectin, nitric oxide (NO), IL-6, MMP-1 and MMP-3 were determined in the culture media. In addition, the effects of adiponectin on the production of NO, IL-6, MMP-1 and MMP-3 were studied in cartilage and in primary chondrocyte cultures.ResultsPlasma adiponectin levels and adiponectin released from OA cartilage were higher in patients with the radiologically most severe OA (Ahlbäck grades 4 and 5) than in patients with less severe disease (Ahlbäck grades 1 to 3). Plasma adiponectin concentrations correlated positively with biomarkers of OA, that is, COMP (r = 0.55, P = 0.001) and MMP-3 (r = 0.34, P = 0.046). Adiponectin was released by OA cartilage ex vivo, and it correlated positively with production of NO (r = 0.43, P = 0.012), IL-6 (r = 0.42, P = 0.018) and MMP-3 (r = 0.34, P = 0.051). Furthermore, adiponectin enhanced production of NO, IL-6, MMP-1 and MMP-3 in OA cartilage and in primary chondrocytes in vitro in a mitogen-activated protein kinase (MAPK)-dependent manner.ConclusionsThe findings of this study show that adiponectin is associated with, and possibly mediates, cartilage destruction in OA.

Preoperative hyperglycemia predicts infected total knee replacement

BACKGROUND Diabetes increases the risk of surgical site infections. In many patients undergoing total knee replacement, however, diabetes has not been diagnosed. The purpose of this study was to analyze the applicability of preoperative screening for hyperglycemia in identifying patients predisposed to infected knee replacement. METHODS A recent series of 1565 primary total knee replacements performed due to osteoarthritis in a specialized, publicly funded hospital for joint replacement was reviewed. RESULTS Preoperative hyperglycemia was significantly associated with infected knee replacement: during the 1-year follow-up infection occurred in 0.44%, 0.93% and 2.42% of patients with preoperative plasma glucose <6.1 mmol/l (<110 mg/dl), 6.1-6.9 mmol/l (110-125 mg/dl) and > or =7.0 mmol/l (> or =126 mg/dl). In age- and gender-adjusted analysis the patients with the highest glucose levels had a 4-fold risk for infected knee replacement compared to the patients with the lowest glucose. Obesity increased the risk of infected knee replacement, but the effect of hyperglycemia on the infection rates remained significant also after adjustment for body mass index. None of the patients with normal but 2.8% of patients with increased glycosylated hemoglobin (>6.5%) experienced infected knee replacement. CONCLUSION Obesity and hyperglycemia associate with a higher risk of infected knee replacement. Preoperative screening of plasma glucose is an efficient way to identify patients in increased risk of infection following primary total knee replacement.

The role of nitric oxide in osteoarthritis

Elevated levels of markers of nitric oxide (NO) production are found in osteoarthritic joints suggesting that NO is involved in the pathogenesis of osteoarthritis (OA). In OA, NO mediates many of the destructive effects of interleukin‐1 (IL‐1) and tumour necrosis factor‐α (TNF‐α) in the cartilage, and inhibitors of NO synthesis have demonstrated retardation of clinical and histological signs and symptoms in experimentally induced OA and other forms of arthritis. As an important factor in cartilage, the regulation of inducible nitric oxide synthase (iNOS) expression and activity, and the effects of NO are reviewed, especially in relation to the pathogenesis of OA.

Alarming wear of the first-generation polyethylene liner of the cementless porous-coated Biomet Universal cup: 107 hips followed for mean 6 years.

Aim : To evaluate epidemiology, prognosis and diagnostics in metastatic bone disease and identify risk factors for failure after operation for pathologic fracture. Patients : The study was based on patients treated for skeletal metastases, myeloma or lymphoma between 1986 and 1998 at the Oncology Service, Department of Orthopedics, Karolinska Hospital and on patients diagnosed with symptomatic skeletal metastases 1989-1994 in the Stockholm Region. Epidemiology : 641 breast cancer patients were diagnosed with symptomatic skeletal metastases 1989-1994. Based upon 1100 new primary breast cancer cases yearly, the overall risk of developing symptomatic skeletal metastases was 10-15%. One out of 5 patients with skeletal metastases required surgical treatment for skeletal complications. Prognosis : The survival rate after surgical treatment for skeletal complications was 0.3 at 1 year and 0.008 at 3 years. Multivariate analysis based on 619 patients showed that complete pathologic fracture and soft tissue metastases were negative prognostic variables for 1-year survival after operation. Solitary skeletal metastasis, breast, prostate, kidney cancer, myeloma, and lymphoma were positive variables. Diagnosis : Fine Needle Aspiration Biopsy (FNAB) was assessed in 110 patients for diagnostic accuracy and to which extent information about primary site of the metastatic carcinoma could be gained. There were 80 patients with metastatic carcinoma, 14 with lymphoma, and 16 with myeloma. FNAB offered correct diagnosis in 9 of 10 patients and also provided guidance in the search for the primary lesions. Hence, 27 of 30 myeloma or lymphomas were diagnosed by FNAB and in half of the patients with metastatic carcinoma the site of the primary tumor could be ascertained. For patients with a suspected skeletal metastasis the search for the primary tumor may preferably start with FNAB. Surgical treatment : Risk factors for failure after operation for pathologic fractures were identified in 192 patients treated for 228 metastatic lesions of the long bones. 26 out of 228 procedures (11%) lead to failures necessitating reoperation. Long survival after surgery was the most important risk factor for failure of the reconstruction. Kidney cancer was the primary tumor associated with the highest rate of reoperations. Reoperations were more common in the femur than in the humerus. Reconstructions based on prosthetic as opposed to osteosynthetic devices appeared safer. There was a tendency for a high reoperation rate in hospitals with few treated patients. Conclusion : To decrease the risk of reoperation, it is important to identify patients with a long expected survival. Patients with a good prognosis should be considered for wide resection and reconstruction as applied in primary malignant bone tumors.Wear of the socket liner and resulting osteolysis are the major causes of failure in cementless hip arthroplasties. We report alarming wear of the first-generation polyethylene liner of the cementless porous-coated Biomet Universal cup. Radiographs of 107 primary hip arthroplasties were analyzed retrospectively. The mean follow-up time was 74 (47-91) months. The linear wear of the polyethylene liners was assessed using a modification of the Livermore method. The median linear wear was 1.0 (0-6.2) and the median linear wear rate was 0.17 mm/year. There was a statistically significant difference between the 28 mm and 32 mm femoral head groups both in the volumetric wear and in the volumetric wear rate. The median linear wear was 0.28 mm/year and 0.14 mm/year for the 32 mm and 28 mm heads, respectively. So far, 14 revisions have been performed or have been scheduled because of excessive wear of the polyethylene liner. In regression analysis, the factors related to the wear rate were the 32 mm size of the femoral head and screw fixation of acetabular shell. We found that the cases with calcar rounding were associated with significantly greater wear. Possible reasons for increased wear of the Hexloc liner may be the cylindrical design, thin polyethylene, and poor quality of the polyethylene. Regular clinical and radiographic follow-ups are recommended especially for hips with 32 mm femoral heads or with screw fixation. If progressive wear of the liner is observed, revision must be considered.Aim : To evaluate epidemiology, prognosis and diagnostics in metastatic bone disease and identify risk factors for failure after operation for pathologic fracture. Patients : The study was based on patients treated for skeletal metastases, myeloma or lymphoma between 1986 and 1998 at the Oncology Service, Department of Orthopedics, Karolinska Hospital and on patients diagnosed with symptomatic skeletal metastases 1989-1994 in the Stockholm Region. Epidemiology : 641 breast cancer patients were diagnosed with symptomatic skeletal metastases 1989-1994. Based upon 1100 new primary breast cancer cases yearly, the overall risk of developing symptomatic skeletal metastases was 10-15%. One out of 5 patients with skeletal metastases required surgical treatment for skeletal complications. Prognosis : The survival rate after surgical treatment for skeletal complications was 0.3 at 1 year and 0.008 at 3 years. Multivariate analysis based on 619 patients showed that complete pathologic fracture and soft tissue metast...