Paul E. Di Cesare

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.

Scaffolds for Articular Cartilage Repair

Tissue engineering of articular cartilage seeks to restore the damaged joint surface, inducing repair of host tissues by delivering repair cells, genes, or polypeptide stimulatory factors to the site of injury. A plethora of devices and materials are being examined for their potential to deliver these agents to wound sites, and to act as scaffolds for ingrowth of new tissue. This review will discuss various promising scaffolds for cartilage tissue engineering applications.

Serum interleukin-6 as a marker of periprosthetic infection following total hip and knee arthroplasty.

BACKGROUND The erythrocyte sedimentation rate, the C-reactive protein serum level, and the white blood-cell count are routinely used to diagnose periprosthetic infection. In the present study, the diagnostic accuracy of the interleukin-6 serum level was compared with the accuracy of these standard tests for the evaluation of a group of patients who had had a total hip or total knee arthroplasty and were undergoing a reoperation for the treatment of an infection or another implant-related problem. METHODS A prospective, case-control study of fifty-eight patients who had had a total hip or knee replacement and were undergoing a reoperation because of an infection (seventeen patients) or another implant-related problem (forty-one patients) was conducted. The serum levels of interleukin-6 and C-reactive protein, the erythrocyte sedimentation rate, and the white blood-cell count were measured. The definitive diagnosis of an infection was determined on the basis of positive histopathological evidence of infection and growth of bacteria on culture of intraoperative specimens. Two-sample Wilcoxon rank-sum (Mann-Whitney) tests were used to determine the presence of a significant difference between patients with and without infection with regard to each laboratory value studied. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of each text were also calculated. RESULTS The serum interleukin-6 level, erythrocyte sedimentation rate, and C-reactive protein level were significantly higher in patients who had an infection than in those who did not, both when all patients were considered together and when the total hip arthroplasty and total knee arthroplasty groups were considered separately. With the numbers available, there was no significant difference with regard to the white blood-cell count between patients with and without infection. With a normal serum interleukin-6 level defined as <10 pg/mL, the serum interleukin-6 test had a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 1.0, 0.95, 0.89, 1.0, and 97%, respectively. CONCLUSIONS An elevated serum interleukin-6 level correlated positively with the presence of periprosthetic infection in patients undergoing a reoperation at the site of a total hip or knee arthroplasty. The serum interleukin-6 level is valuable for the diagnosis of periprosthetic infection in patients who have had a total hip or total knee arthroplasty.

Stiffness After Total Knee Arthroplasty

Abstract Postoperative stiffness is a debilitating complication of total knee arthroplasty. Preoperative risk factors include limited range of motion, underlying diagnosis, and history of prior surgery. Intraoperative factors include improper flexion‐extension gap balancing, oversizing or malpositioning of components, inadequate femoral or tibial resection, excessive joint line elevation, creation of an anterior tibial slope, and inadequate resection of posterior osteophytes. Postoperative factors include poor patient motivation, arthrofibrosis, infection, complex regional pain syndrome, and heterotopic ossification. The first steps in treating stiffness are mobilizing the patient and instituting physical therapy. If these interventions fail, options include manipulation, lysis of adhesions, and revision arthroplasty. Closed manipulation is most successful within the first 3 months after total knee arthroplasty. Arthroscopic or modified open lysis of adhesions can be considered after 3 months. Revision arthroplasty is preferred for stiffness from malpositioned or oversized components. Patients who initially achieve adequate range of motion (>90° of flexion) but subsequently develop stiffness more than 3 months after surgery should be assessed for intrinsic as well as extrinsic causes.

Use of Antibiotic-Impregnated Cement in Total Joint Arthroplasty

&NA; The use of antibiotic‐impregnated cement in revision of total hip arthroplasty procedures is widespread, and a substantial body of evidence demonstrates its efficacy in infection prevention and treatment. However, it is not clear that it is necessary or desirable as a routine means of prophylaxis in primary total joint arthroplasty. In the management of infected implant sites, antibioticimpregnated cement used in one‐stage exchange arthroplasties has lowered reinfection rates. In two‐stage procedures, use of beads and either articulating or nonarticulating antibiotic‐impregnated cement spacers also has lowered reinfection rates. In addition, spacers reduce “dead space,” help stabilize the limb, and facilitate reimplantation. Problems associated with antibiotic‐impregnated cement in total joint arthroplasty include weakening of the cement and the generation of antibiotic‐resistant bacteria in infected implant sites.

Periprosthetic Femoral Fractures Above Total Knee Replacements

Abstract Periprosthetic femoral fractures above total knee replacements can be managed by a variety of methods, including casting, open reduction and internal fixation, external fixation, or revision arthroplasty. Because no single method has emerged as the optimal choice for all such fractures, it is important to understand which options are appropriate for each fracture pattern. Early classification systems focused on displacement as a major indication for either surgical or nonsurgical management. However, recent techniques and current implants have made surgical management preferable for most periprosthetic fractures. Classification based on fracture location can help guide such treatment. Generally, intramedullary nails are best for proximal fractures, fixed‐angle devices for fractures originating at the component, and revision arthroplasty for very distal fractures or those with implant loosening.

Analysis of Frozen Sections of Intraoperative Specimens Obtained at the Time of Reoperation After Hip or Knee Resection Arthroplasty for the Treatment of Infection

BACKGROUND Despite the effectiveness of a two-stage exchange protocol for the treatment of deep periprosthetic infection, infection can persist after resection arthroplasty and treatment with antibiotics, leading to a failed second-stage reconstruction. Intraoperative analysis of frozen sections has been shown to have a high sensitivity and specificity for the identification of infection at the time of revision arthroplasty; however, the usefulness of this test at the time of reoperation after resection arthroplasty and treatment with antibiotics is, to our knowledge, unknown. METHODS The medical records of sixty-four consecutive patients who had had a resection arthroplasty of either the knee (thirty-three patients) or the hip (thirty-one patients) and had had intraoperative analysis of frozen sections of periprosthetic tissue obtained at the time of a second-stage operation were reviewed. The mean interval between the resection arthroplasty and the attempted reimplantation was nineteen weeks. The results of the intraoperative analysis of the frozen sections were compared with those of analysis of permanent histological sections of the same tissues and with those of intraoperative cultures of specimens obtained from within the joint. The findings of the analyses of the frozen sections and the permanent histological sections were considered to be consistent with acute inflammation and infection if a mean of ten polymorphonuclear leukocytes or more per high-power field (forty times magnification) were seen in the five most cellular areas. RESULTS The intraoperative frozen sections of the specimens from two patients (one of whom was considered to have a persistent infection) met the criteria for acute inflammation. Four patients were considered to have a persistent infection on the basis of positive intraoperative cultures or permanent histological sections. Overall, intraoperative analysis of frozen sections at the time of reimplantation after resection arthroplasty had a sensitivity of 25 percent (detection of one of four persistent infections), a specificity of 98 percent, a positive predictive value of 50 percent (one of two), a negative predictive value of 95 percent, and an accuracy of 94 percent. CONCLUSIONS A negative finding on intraoperative analysis of frozen sections has a high predictive value with regard to ruling out the presence of infection; however, the sensitivity of the test for the detection of persistent infection is poor.

Matrix metalloproteinases 19 and 20 cleave aggrecan and cartilage oligomeric matrix protein (COMP)

Matrix metalloproteinase (MMP)‐19 and MMP‐20 (enamelysin) are two recently discovered members of the MMP family. These enzymes are involved in the degradation of the various components of the extracellular matrix (ECM) during development, haemostasis and pathological conditions. Whereas MMP‐19 mRNA is found widely expressed in body tissues, including the synovium of normal and rheumatoid arthritic patients, MMP‐20 expression is restricted to the enamel organ. In this study we investigated the ability of MMP‐19 and MMP‐20 to cleave two of the macromolecules characterising the cartilage ECM, namely aggrecan and the cartilage oligomeric matrix protein (COMP). Both MMPs hydrolysed aggrecan efficiently at the well‐described MMP cleavage site between residues Asn341 and Phe342, as shown by Western blotting using neo‐epitope antibodies. Furthermore, the two enzymes cleaved COMP in a distinctive manner, generating a major proteolytic product of 60 kDa. Our results suggest that MMP‐19 may participate in the degradation of aggrecan and COMP in arthritic disease, whereas MMP‐20, due to its unique expression pattern, may primarily be involved in the turnover of these molecules during tooth development.

Cartilage oligomeric matrix protein associates with granulin-epithelin precursor (GEP) and potentiates GEP-stimulated chondrocyte proliferation

Mutations in human cartilage oligomeric matrix protein (COMP) have been linked to the development of pseudoachondroplasia and multiple epiphyseal dysplasia; however, the functions of both wild-type and mutant COMP in the skeletogenesis remain unknown. In an effort to define the biological functions of COMP, a functional genetic screen based on the yeast two-hybrid system was performed. This led to the identification of granulin-epithelin precursor (GEP), an autocrine growth factor, as a COMP-associated partner. COMP directly binds to GEP both in vitro and in vivo, as revealed by in vitro pull down and co-immunoprecipitation assays. GEP selectively interacts with the epidermal growth factor repeat domain of COMP but not with the other three functional domains of COMP. The granulin A repeat unit of GEP is required and sufficient for association with COMP. COMP co-localizes with GEP predominantly in the pericellular matrix of transfected rat chondrosarcoma cell and primary human chondrocytes. Staining of musculoskeletal tissues of day 19 mouse embryo with antibodies to GEP is restricted to chondrocytes in the lower proliferative and upper hypertrophic zones. Overexpression of GEP stimulates the proliferation of chondrocytes, and this stimulation is enhanced by COMP. In addition, COMP appears to be required for GEP-mediated chondrocyte proliferation, since chondrocyte proliferation induced by GEP is dramatically inhibited by an anti-COMP antibody. These findings provide the first evidence linking the association of COMP and GEP and identifying a previously unrecognized growth factor (i.e. GEP) in cartilage.

The predictive value of indium-III leukocyte scans in the diagnosis of infected total hip, knee, or resection arthroplasties

To evaluate the usefulness of the indium-111 scan in detecting actually or potentially infected total hip, knee, and resection arthroplasties, 153 scans were performed on 143 patients who underwent reoperation for a loose or painful total joint arthroplasty or a resection arthroplasty between 1990 and 1996. Scans were interpreted as infected, not infected, or equivocal by an experienced nuclear medicine radiologist. Patients were considered to be infected if they met any 2 of the following criteria: i) positive intraoperative cultures, ii) final permanent histologic section indicating acute inflammation, and iii) intraoperative findings of gross purulence within the joint. Twenty-six patients (17%) met the infection criteria at the time of reoperation. Indium scans were found to have a 77% sensitivity, 86% specificity, 54% and 95% positive and negative predictive values, and 84% accuracy for the prediction of infection. Of 6 equivocal scans, none were infected. The results of this study suggest limited indications for the use of the indium-111 scan in the evaluation of painful hip, knee, or resection arthroplasties. A negative indium scan may be helpful in suggesting the absence of infection in cases in which the diagnosis is not otherwise evident.