Curtis W. Hartman

IL-12 Promotes Myeloid-Derived Suppressor Cell Recruitment and Bacterial Persistence during Staphylococcus aureus Orthopedic Implant Infection

Staphylococcus aureus is a leading cause of human prosthetic joint infections (PJIs) typified by biofilm formation. We recently identified a critical role for myeloid-derived suppressor cells (MDSCs) in S. aureus biofilm persistence. Proinflammatory signals induce MDSC recruitment and activation in tumor models; however, the mechanisms responsible for MDSC homing to sites of biofilm infection are unknown. In this study, we report that several cytokines (IL-12p40, IL-1β, TNF-α, and G-CSF) and chemokines (CXCL2, CCL5) were significantly elevated in a mouse model of S. aureus PJI. This coincided with significantly increased MDSC infiltrates concomitant with reduced monocyte, macrophage, and T cell influx compared with uninfected animals. Of the cytokines detected, IL-12 was of particular interest based on its ability to possess either pro- or anti-inflammatory effects mediated through p35-p40 heterodimers or p40 homodimers, respectively. MDSC recruitment was significantly reduced in both p40 and p35 knockout mice, which resulted in enhanced monocyte and neutrophil influx and bacterial clearance. Adoptive transfer of wild-type MDSCs into infected p40 knockout animals worsened disease outcome, as evidenced by the return of S. aureus burdens to levels typical of wild-type mice. Tissues obtained from patients undergoing revision surgery for PJI revealed similar patterns of immune cell influx, with increased MDSC-like cells and significantly fewer T cells compared with aseptic revisions. These findings reveal a critical role for IL-12 in shaping the anti-inflammatory biofilm milieu by promoting MDSC recruitment.

Femoral fixation in revision total hip arthroplasty.

Recent data project the number of total hip arthroplasty revisions to grow by 137% between 2005 and 20301. Surgeons who manage the failed total hip replacement will find an ever-increasing workload and must have an understanding of the outcomes and treatment options for the failed femoral implant. Management strategies for femoral implant revision are based on the femoral defect and the quality and quantity of the remaining femoral bone stock. Numerous options are available for femoral reconstruction, including cemented fixation, cementless fixation with use of proximally porous-coated implants, cylindrical extensively porous-coated implants, modular and nonmodular tapered fluted stems, impaction bone-grafting, allograft-prosthetic composites, and proximal femoral replacement (megaprostheses). Look for this and other related articles in Instructional Course Lectures , Volume 61, which will be published by the American Academy of Orthopaedic Surgeons in February 2012: Careful preoperative planning is a necessary step before any revision arthroplasty. An attempt should be made to identify the implants being revised. The implant manufacturer should be contacted for implant removal devices that may be specific to the implant being revised. Even when an isolated femoral revision is planned, it is beneficial to identify the acetabular implant, as a modular polyethylene exchange may be possible. The standard evaluation for preoperative planning includes four radiographic views: an anteroposterior view of the pelvis, an anteroposterior view of the affected hip, a frog-leg lateral view, and a shoot-through lateral view of the affected hip2. The radiograph should be examined for areas of osteolysis, stress-shielding, femoral deformity, cortical deficiency, or the amount and location of cement. The radiographs provide substantial information as to the difficulty of implant removal and subsequent reconstruction, while the degree and pattern of bone loss influence the revision implant choice. The …

Low Wear Rates Seen in THAs With Highly Crosslinked Polyethylene at 9 to 14 Years in Patients Younger Than Age 50 Years

BackgroundPatients 50 years or younger are at high risk for wear-related complications of their total hip arthroplasty (THA) because of their generally higher levels of activity. Highly crosslinked polyethylene (HXLPE) is believed to be more durable for this population than conventional polyethylene because of its improved wear; however, limited information is available on the wear of HXLPE in this population, particularly the wear of HXLPE when it articulates with alternative bearings like Oxinium (Smith & Nephew, Memphis, TN, USA).Questions/purposesThe purpose of this study was to evaluate two questions relative to this population of patients undergoing THA. First, what was the linear and volumetric wear rate of HXLPE in patients 50 years or younger at a minimum followup of 9 years and was osteolysis observed in any of these hips? Given the potential for damage to the Oxinium femoral head surface, was the wear of HXLPE in the patients with this material similar to the other bearings or was there accelerated or runaway wear that was visible in any of the patients?MethodsFrom November 1999 to April 2005, 105 THAs were performed in 95 patients 50 years of age or younger (mean, 42 years; range, 20–50 years). The mean body mass index was 30 kg/m2 (range, 17–51 kg/m2).The mean followup was 12 years (range, 9–14 years). Two patients died, five patients (one bilateral) were lost to followup, and one hip was revised elsewhere for pain. The patients’ information was not included in the study, which left 87 patients with 96 hips for analysis. Highly crosslinked polyethylene was the acetabular bearing for all of the hips. We analyzed the linear and volumetric wear of all of the hips using the Martell method. Eighty hips had the same diameter head (28 mm) allowing us to more accurately compare the different bearing materials. The type of femoral head used was related to our sequential use of materials beginning with cobalt chrome (14), ceramic (23) followed by Oxinium (43) in the hips with 28-mm heads. Although cobalt-chrome was used early in this study, our previous experience with ceramic on polyethylene encouraged us to use it as an alternative bearing. The Oxinium was used consecutively for the remaining hips.ResultsThe mean wear of the HXLPE after 1 year of bedding-in (true linear wear)was 0.022 mm/year (95% confidence interval [CI], 0.015–0.030 mm/year). The mean volumetric wear of HXLPE after 1 year of bedding-in (true volumetric wear) was 9 mm3/year (95% CI, 4–14 mm3/year). None of the hip radiographs had evidence of loosening or osteolysis. Wear was not associated with femoral head material (p = 0.58 for linear wear/year versus head material and p = 0.52 for volumetric wear/year versus head material).ConclusionsIn our study of patients 50 years of age or younger undergoing THA, the linear and volumetric wear rates of HXLPE were very low regardless of the bearing surface material. The laboratory concerns of Oxinium surface damage are serious but at this time we have not seen high wear of the HXLPE or osteolysis in this population.Level of EvidenceLevel III, therapeutic study.

Dislocation of the hip after reimplantation for infection: An analysis of risk factors

Dislocation is a well documented complication after a two-stage revision arthroplasty for a deep periprosthetic hip infection. We are aware of no reports specifically evaluating the risk factors for dislocation after reimplantation for infection. We hypothesized greater age, increase in the number of operations on the hip, increase in the length of time from resection to reimplantation, greater limb length discrepancy, smaller femoral offset, and using smaller femoral heads would increase the risk of dislocation. We retrospectively reviewed 34 patients who had a two-stage hip revision for periprosthetic infection with a minimum followup of 2 years. Risk factors for dislocation were evaluated. We compared the rate of dislocation in this group to those patients having revision for aseptic failure. Sixteen dislocations occurred in five (14.7%) of 34 patients. Dislocation occurred in three (1.7%) of 171 patients having revision for aseptic failure. In this small series, age at reimplantation, number of previous operations on the hip, length of time from resection to reimplantation, limb length discrepancy, femoral offset, and femoral head size did not seem to be risk factors for dislocation.Level of Evidence: Therapeutic study, level III (case-control study). See Guidelines for Authors for a complete description of levels of evidence.

Revision Total Knee Arthroplasty for Stiffness

Few studies have evaluated the results of revision of well-fixed components for stiffness, and some authors have recommended against this intervention based on poor reported results. Thirty-five consecutive patients underwent revision of both femoral and tibial components for stiffness. At a mean of 54.5 months (range, 25-134), the mean arc of motion improved by 44.5 degrees from a preoperative mean of 53.6 degrees to a postoperative mean of 98.1 degrees (P < .0001). The arc of motion improved by more than 30 degrees in 75% (24/32) of patients evaluated at a minimum of 2 years. Seventeen (49%) of the 35 patients required a further intervention for stiffness or sustained a complication. These results suggest that revision total knee arthroplasty for stiffness can be performed with a reasonable expectation of improvement, although the risk of complications and additional operative procedures is substantial.

Impact of Total Knee Arthroplasty as Assessed Using Patient-Reported Pain and Health-Related Quality of Life Indices: Rheumatoid Arthritis Versus Osteoarthritis

To assess and compare the impact of total knee arthroplasty (TKA) in patients with rheumatoid arthritis (RA) and patients with osteoarthritis (OA).

The Mark Coventry, MD, Award: Oral Antibiotics Reduce Reinfection After Two-Stage Exchange: A Multicenter, Randomized Controlled Trial

BackgroundMany patients develop recurrent periprosthetic joint infection after two-stage exchange arthroplasty of the hip or knee. One potential but insufficiently tested strategy to decrease the risk of persistent or recurrent infection is to administer additional antibiotics after the second-stage reimplantation.Questions/purposes(1) Does a 3-month course of oral antibiotics decrease the risk of failure secondary to infection after a two-stage exchange? (2) Are there any complications related to the administration of oral antibiotics after a two-stage exchange? (3) In those patients who develop a reinfection, is the infecting organism different from the initial infection?MethodsPatients at seven centers randomized to receive 3 months of oral antibiotics or no further antibiotic treatment after operative cultures after the second-stage reimplantation were negative. Adult patients undergoing two-stage hip or knee revision arthroplasty for a periprosthetic infection who met Musculoskeletal Infection Society (MSIS) criteria for infection at the first stage were included. Oral antibiotic therapy was tailored to the original infecting organism(s) in consultation with an infectious disease specialist. MSIS criteria as used by the treating surgeon defined failure. Surveillance of patients for complications, including reinfection, occurred at 3 weeks, 6 weeks, 3 months, 12 months, and 24 months. If an organism demonstrated the same antibiotic sensitivities as the original organism, it was considered the same organism; no DNA subtyping was performed. Analysis was performed as intent to treat with all randomized patients included in the groups to which they were randomized. A log-rank survival curve was used to analyze the primary outcome of reinfection. At planned interim analysis (enrollment is ongoing), 59 patients were successfully randomized to the antibiotic group and 48 patients to the control group. Fifty-seven patients had an infection after TKA and 50 after a THA. There was no minimum followup for inclusion in this analysis. The mean followup was 14 months in the antibiotic group and 10 months in the control group.ResultsPatients treated with oral antibiotics failed secondary to infection less frequently than those not treated with antibiotics (5% [three of 59] versus 19% [nine of 48]; hazard ratio, 4.37; 95% confidence interval, 1.297–19.748; p = 0.016). Three patients had an adverse reaction to the oral antibiotics severe enough to cause them to stop taking the antibiotics early, and four patients who were randomized to that group did not take the antibiotics as directed. With the numbers available, there were no differences between the study groups in terms of the likelihood that an infection after treatment would be with a new organism (eight of nine in the control group versus one of three in the treatment group, p = 0.087).ConclusionsThis multicenter randomized trial suggests that at short-term followup, the addition of 3 months of oral antibiotics appeared to improve infection-free survival. As a planned interim analysis, however, these results may change as the study reaches closure and the safety profile may yet prove risky. Further followup of this cohort of patients will be necessary to determine whether these preliminary results are durable over time.Level of EvidenceLevel I, therapeutic study.

Mouse model of post-arthroplasty Staphylococcus epidermidis joint infection.

Animal models are invaluable tools for translational research, allowing investigators to recapitulate observed clinical scenarios within the laboratory that share attributes with human disease. Here, we describe a mouse model of post-arthroplasty Staphylococcus epidermidis joint infection which mimics human disease and may be utilized to explore the complex series of events during staphylococcal implant-associated infections by identifying key immunological, bacterial, and/or therapeutic mechanisms relevant to these persistent infections.

Vascular Management in Rotationplasty

AbstractThe Van Nes rotationplasty is a useful limb-preserving procedure for skeletally immature patients with distal femoral or proximal tibial malignancy. The vascular supply to the lower limb either must be maintained and rotated or transected and reanastomosed. We asked whether there would be any difference in the ankle brachial index or complication rate for the two methods of vascular management. Vessels were resected with the tumor in seven patients and preserved and rotated in nine patients. One amputation occurred in the group in which the vessels were preserved. Four patients died secondary to metastatic disease diagnosed preoperatively. The most recent ankle brachial indices were 0.96 and 0.82 for the posterior tibial and dorsalis pedis arteries, respectively, in the reconstructed group. The ankle brachial indices were 0.98 and 0.96 for the posterior tibial and dorsalis pedis arteries, respectively, in the rotated group. Outcomes appear similar using both methods of vascular management and one should not hesitate to perform an en bloc resection when there is a question of vascular involvement. Level of Evidence: Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

The pharmacology of infection after total joint arthroplasty

Choosing appropriate antimicrobial therapy for prosthetic joint infections is a multifactorial and often complicated process. Factors that influence antimicrobial decision-making include pharmacodynamics, choice of surgical management, patient tolerance and allergy, financial considerations, and convenience of dosing. Recommendations regarding antimicrobial therapy for prosthetic joint infections vary greatly, and studies to define optimal therapy are lacking. Over the past 10 years, most of the literature on the treatment of prosthetic joint infection has focused on the utility of combination antimicrobial therapy and newer agents to combat multidrug-resistant pathogens.