Risk of Periprosthetic Joint Infection After Intra-Articular Corticosteroid Injection Following Unicompartmental Knee Arthroplasty.

BACKGROUND: Perioperative intra-articular joint injection is a known risk factor for developing prosthetic joint infection (PJI) in the immediate preoperative and postoperative periods for total knee arthroplasty, but is less defined in unicompartmental knee arthroplasty (UKA). The goal of this study was to elucidate the risk of developing PJI after intra-articular corticosteroid injection (IACI) into a post UKA knee. METHODS: A retrospective review of a nationwide administrative claims database was performed from January 2015 to October 2020. Patients who underwent UKA and had an ipsilateral IACI were identified and matched 2:1 to a control group of primary UKA patients who did not receive IACI. Multivariate logistic analyses were conducted to assess differences in PJI rates at 6 months, 1 year, and 2 years. RESULTS: A total of 47,903 cases were identified, of which 2,656 (5.5%) cases received IACI. The mean time from UKA to IACI was 355 days. The incidence of PJI in the IACI group was 2.7%, compared to 1.3% in the control group. The rate of PJI after IACI was significantly higher than the rate in the control group at 6 months, 1 year, and 2 years (all P < .05). The majority of PJI occurred within the first 6 months following IACI (75%). CONCLUSION: In this study, IACI in a UKA doubled the risk of PJI compared to patients who did not receive an injection. Surgeons should be aware of this increased risk to aid in their decision-making about injecting into a UKA. LEVEL OF EVIDENCE: III, retrospective comparative study.

Proton-pump inhibitors are associated with increased risk of prosthetic joint infection in patients with total hip arthroplasty: a case-cohort study.

Background and purpose - Proton-pump inhibitors (PPI) have previously been associated with an increased risk of infections such as community-acquired pneumonia, gastrointestinal infections and central nervous system infection. Therefore, we evaluated a possible association between proton-pump inhibitor use and prosthetic joint infection (PJI) in patients with total hip arthroplasty (THA), because they can be stopped perioperatively or switched to a less harmful alternative.Patients and methods - A cohort of 5,512 primary THAs provided the base for a case-cohort design; cases were identified as patients with early-onset PJI. A weighted Cox proportional hazard regression model was used for the study design and to adjust for potential confounders.Results - There were 75 patients diagnosed with PJI of whom 32 (43%) used PPIs perioperatively compared with 75 PPI users (25%) in the control group of 302 patients. The risk of PJI was 2.4 times higher (95% CI 1.4-4.0) for patients using PPI. This effect remained after correction for possible confounders.Interpretation - The use of PPIs was associated with an increased risk of developing PJI after THA. Hence, the use of a PPI appears to be a modifiable risk factor for PJI.

The Effects of Peri-Operative Dexamethasone on Patients Undergoing Total Hip or Knee Arthroplasty: Is It Safe for Diabetics?

BACKGROUND: Peri-operative dexamethasone has been shown to effectively reduce post-operative nausea and vomiting and aide in analgesia after total joint arthroplasty (TJA); however, systemic glucocorticoid therapy has many adverse effects. The purpose of this study is to determine the effects of dexamethasone on prosthetic joint infection (PJI) and blood glucose levels in patients undergoing TJA. METHODS: A retrospective chart review of all patients receiving primary TJA from 2011 to 2015 (n = 2317) was conducted. Patients were divided into 2 cohorts: dexamethasone (n = 1426) and no dexamethasone (n = 891); these groups were subdivided into diabetic and non-diabetic patients. The primary outcome was PJI; secondary measures included glucose levels and pre-operative hemoglobin A1c (A1c) values. Statistics were carried out using logistic and regression models. RESULTS: Of the 2317 joints, 1.12% developed PJI; this was not affected by dexamethasone (P = .166). Diabetics were found to have higher rate of infection (P < .001); however, diabetics who received dexamethasone were not found to have a significantly higher infection rate that non-diabetics (P = .646). Blood glucose levels were found to increase post-operatively, and dexamethasone did not increase this change (P = .537). Diabetes (P < .001) and increasing hemoglobin A1c (P < .001) were also associated with increased serum glucose levels; however, this was not influenced by dexamethasone (P = .595). CONCLUSION: Although diabetic patients were found to have a higher infection rate overall, this was not affected by administration of intravenous dexamethasone, nor was the post-operative elevation in serum glucose levels. In this study population, peri-operative intravenous dexamethasone did not increase the rate of PJI and was safe to administer in patients undergoing TJA.

Infection safety of dexamethasone in total hip and total knee arthroplasty: a study of eighteen thousand, eight hundred and seventy two operations.

PURPOSE: Dexamethasone has been shown to prevent post-operative nausea and vomiting (PONV) and seems to reduce post-operative pain. Both factors, which can extend the hospital stay, delay rehabilitation, and impact patient satisfaction. Because of the immunosuppressive and glucose-rising effects of dexamethasone, there has been concern of its safety in arthroplasty surgery. The purpose of our study was to examine infection safety of dexamethasone in arthroplasty surgery with enough large study material to reliably detect a possible, even small, difference in infection incidence. METHODS: A total of 18,872 consecutive primary and revision hip and knee arthroplasties were analyzed with data gathered from clinical information databases and a surgical site infection surveillance database with prospective data collection. Also, emergency operations due to fractures were included except for hip hemiarthroplasties. RESULTS: During the follow-up, 189 (1.0%) prosthetic joint infections (PJIs) occurred: 0.8% after primary arthroplasty and 1.9% after revision arthroplasty. Dexamethasone was used in 2922 (15.5%) operations. The PJI rate in the dexamethasone group was 1.1% (31/2922) and in the non-dexamethasone group 1.0% (161/15950), with no significant difference in the risk of PJI between the two groups (OR 1.052, 95% CI 0.715-1.548, P = 0.773). CONCLUSIONS: In our study material, the use of a single 5-10 mg dose of dexamethasone did not increase the incidence of post-operative PJI. A low dose of dexamethasone may be safely used to prevent PONV and as part of multimodal analgesia on patients undergoing arthroplasty operation.

Preoperative Opioids Increase the Risk of Periprosthetic Joint Infection After Total Joint Arthroplasty.

BACKGROUND: Opioids have well-known immunosuppressive properties and preoperative opioid consumption is relatively common among patients undergoing total joint arthroplasty (TJA). The hypothesis of this study was that utilization of opioids preoperatively would increase the incidence of subsequent periprosthetic joint infection (PJI) in patients undergoing primary TJA. METHODS: A comparative cohort study design was set up that used a cohort of 23,754 TJA patients at a single institution. Patient records were reviewed to extract relevant information, in particular details of opioid consumption, and an internal institutional database of PJI was cross-referenced against the cohort to identify patients who developed a PJI within 2 years of index arthroplasty. Univariate and multivariate linear regression analyses were used to examine the potential association between preoperative opioid consumption and the development of PJI. RESULTS: Among the total cohort of 23,754 patients, 5051 (21.3%) patients used opioids before index arthroplasty. Preoperative opioid usage overall was found to be a significant risk factor for development of PJI in the univariate (odds ratio, 1.63; P = .005) and multivariate analyses (adjusted odds ratio, 1.53 [95% confidence interval, 1.14-2.05], P = .005). CONCLUSION: Preoperative opioid consumption is independently associated with a higher risk of developing a PJI after primary TJA. These findings underscore a need for caution when prescribing opioids in patients with degenerative joint disease who may later require arthroplasty.

Does Timing of Previous Intra-Articular Steroid Injection Affect the Post-Operative Rate of Infection in Total Knee Arthroplasty?

Intra-articular steroid injections are widely used for symptomatic relief of knee osteoarthritis. This study used a national database to determine if there is an association between preoperative intra-articular knee injection at various time intervals prior to ipsilateral TKA and infection. The incidence of infection within 3 months (2.6%, OR 2.0 [1.6-2.5], P < 0.0001) and 6 months (3.41%, OR 1.5 [1.2-1.8], P < 0.0001) after TKA within 3 months of knee injection was significantly higher than our control cohort. There was no significant difference in patients who underwent TKA more than 3 months after injection. Ipsilateral knee injection within three months prior to TKA is associated with a significant increase in infection.

Total joint arthroplasty following intra-articular steroid injection: a literature review.

This study aimed to identify, by systematic review of the literature, whether intra-articular steroid injection before total joint replacement confers an increased risk of post-operative deep prosthetic infection. All studies assessing the incidence of deep prosthetic infection in patients who had undergone steroid injection in the same joint were included. A mixed meta-analysis and narrative review of 12 studies with 2068 participants was conducted. Steroid injection prior to total joint replacement was found to confer no increased risk of deep or superficial prosthetic infection (CI = 95%). We found no evidence of a link between injection and deep joint infection, and conclude that this is a safe procedure when conducted with aseptic precautions. We suggest a prospective randomised control trial to provide conclusive data on this question.

Safety and efficacy of intravesical bacillus Calmette-Guérin plus interferon α-2b therapy for nonmuscle invasive bladder cancer in patients with prosthetic devices.

PURPOSE: Patients with bladder cancer who have prosthetic devices, such as a cardiac pacemaker, artificial heart valve or orthopedic hardware, and who undergo intravesical bacillus Calmette-Guérin therapy are theoretically at higher risk for complications, including bacterial seeding of pacemaker wires or orthopedic hardware, and at further risk for infective endocarditis. We assessed the safety and efficacy of bacillus Calmette-Guérin plus interferon α-2b therapy in patients with nonmuscle invasive bladder cancer and a pacemaker, artificial heart valve or orthopedic hardware. MATERIALS AND METHODS: We evaluated 1,045 patients with nonmuscle invasive bladder cancer enrolled in a multicenter American phase II trial of bacillus Calmette-Guérin plus interferon α-2b therapy, including 143 with a prosthetic device (pacemaker in 87, artificial heart valve in 13 and orthopedic hardware in 43). Weekly physician toxicity assessments and standard adverse effect reporting were done. RESULTS: No patient had infective endocarditis or hardware infection. One patient with a pacemaker, 2 with orthopedic hardware and none with an artificial heart valve required treatment cessation for fever greater than 102.5F. All defervesced within 24 hours and had no long-term sequelae. Due to intolerable, nonlife threatening side effects 12 patients with a pacemaker, 2 with orthopedic hardware and 1 with an artificial heart valve stopped treatment. Of the remaining patients with a prosthesis 99 and 24 stopped treatment due to intolerable, nonlife threatening and serious side effects, respectively. CONCLUSIONS: Patients with a pacemaker, artificial heart valve or orthopedic hardware were no more likely than the general population to have infection or fever, or discontinue treatment due to side effects. These patients should not be excluded from intravesical bacillus Calmette-Guérin plus interferon α-2b therapy for nonmuscle invasive bladder cancer.

Late infection of total knee arthroplasty inflamed by anti-TNFalpha, Infliximab therapy in rheumatoid arthritis.

We report a case of sudden onset of late infection after TKA inflamed by anti-TNFalpha therapy, Infliximab, in a 54-year-old woman with RA. Infliximab therapy was started 3 years and 8 months after TKAs as a result of multiple arthritides showing high inflammation of RA. One week after the third administration of Infliximab, the patient suffered sudden knee pain and infectious clinical symptoms, and bacteria (MSSA) were detected by joint effusion culture. She was successfully treated by open debridement with antibiotics-loaded calcium phosphate bone paste and cement and the prostheses were retained. Early diagnosis and operative treatment might be the key to controlling infected TKA without removing the implant. This present case might indicate a serious risk of immunosuppressive effects caused by Infliximab.

Infection in knee replacements after previous injection of intra-articular steroid.

We reviewed 231 patients who had undergone total knee replacement with an AGC (Biomet) implant over a period of 2.5 years. After applying exclusion criteria and with some loss to follow-up, there were 144 patients available for study. These were divided into two groups; those who had received intra-articular steroid in the 11 months before surgery and those who had not. There were three deep infections, all of which occurred in patients who had received a steroid injection. The incidence of superficial infection was not significantly different in the two groups. Five patients had undergone investigation for suspected deep infection because of persistent swelling or pain and all of these had received an intra-articular injection pre-operatively. We conclude that the decision to administer intra-articular steroids to a patient who may be a candidate for total knee replacement should not be taken lightly because of a risk of post-operative deep infection.

Development and problems of metal-on-metal hip arthroplasty.

For over 40 years, the metal-on-polyethylene bearing has dominated the field of total hip replacement. Problems of wear, osteolysis (dissolution of bone), and ultimately failure of prostheses have led to the development of alternative bearing surfaces. Metal-on-metal hip resurfacing has taken current orthopaedic surgery almost by storm. However, metal ion release following metal-on-metal hip resurfacing remains a major cause for concern. This article looks into the development and examines problems and issues surrounding metal-on-metal resurfacing arthroplasty.

The clinical significance of metal ion release from cobalt-chromium metal-on-metal hip joint arthroplasty.

Metal-on-metal (MOM) bearings offer extremely low wear and the avoidance of polyethylene but generate metallic wear particles. Although their total volume is dramatically smaller than polyethylene debris, these particles are in the nanometre size range and are many times more numerous. Metallic particles are ingested by macrophages or may be disseminated via lymphatics to the reticuloendothelial system. They corrode, and metal ions are present in the circulation and concentrated in erythrocytes. Excretion of metal ions via the kidneys seems to balance their generation in patients with MOM implants. However, highly sensitive detection methods can be used to show that levels of circulating cobalt and chromium ions are several times the normal level. These concentrations are well within the limits identified as dangerous to health in workers exposed to industrial chemicals, and also considerably lower than the levels found to cause cell toxicity in vitro. The local concentrations of particles and metal ions in the synovial tissue may occasionally exceed these limits and cause tissue necrosis. Clinical experience of lysis is rare in association with MOM bearings, as are hypersensitivity reactions and MOM bearings have had an excellent record over four decades and have a favourable benefit to risk ratio. Further reduction in risk will be achieved by improvement of materials, engineering, and accuracy of insertion.

Biological effects of metal-on-metal hip replacements.

The advantages seen by patients receiving total hip arthroplasties and the implications of the release of both metal particles and soluble metal ions are discussed. This paper describes some of the early changes that have been observed in metal-on-metal hip arthroplasties, in terms of both changes in metal levels in blood and chromosome changes.

Synergistic effects of mixed TiAlV and polyethylene wear particles on TNFalpha response in THP-1 macrophages.

TNFalpha is a potent osteoclastogenic cytokine that has a fundamental role in the pathogenesis of wear particle-induced osteolysis. Wear particles of one composition and their biological effects are well characterised. In contrast, little is known about the effects of mixed particles with respect to mix ratio and particle concentration. We evaluated the effects of different mix ratios of polyethylene and TiAlV particles on TNFalpha response. We used a human monocytic cell line (THP-1) in this in vitro study. THP-1 monocytes were differentiated to macrophage-like cells and exposed to different mixtures of lipopolysaccharide-detoxified polyethylene and TiAlV particles. TNFalpha was analysed in culture supernatants using ELISAs. Both polyethylene and TiAlV particles induced a dose- and time-related release of TNFalpha, with maximum levels after 6 h. A PE/TiAlV mix ratio of 36:1 at 10(8) particles/ml induced significantly higher TNFalpha concentrations compared to equal particle concentrations of isolated TiAlV (p=0.047) or PE (p=0.044), indicating the synergistic effect of mixed particles. These results provide evidence that TiAlV and polyethylene particles have significant synergistic effects, depending on the mix ratio and particle concentrations. This supra-additive effect can contribute substantially to the pathogenesis of implant particle-induced osteolysis.

The effect of simvastatin on polyethylene particle-induced osteolysis.

This study aimed to investigate the effects of the HMG-CoA reductase inhibitor simvastatin on ultra-high molecular weight polyethylene (UHMWPE) particle-induced osteolysis. The murine calvarial osteolysis model was used in 21 C57BL/J6 mice randomized to three groups. Group I underwent sham surgery only, group II received UHMWPE particles, and group III, particles and simvastatin treatment. After two weeks, calvaria were processed for histomorphometry. Bone resorption was measured as resorption within the midline suture using Giemsa staining. Osteoclast numbers were determined per high-power field using TRAP-staining. Statistical analysis was performed using one-way ANOVA and Student's t-test. Bone resorption in midline suture was 0.094+/-0.007 mm(2) in sham controls (group I), 0.25+/-0.025 mm(2) after particle implantation without further intervention (group II), and 0.131+/-0.02 mm(2) with particle implantation and additional simvastatin treatment (group III) (p=0.00003). Osteoclast numbers were 15.3+/-3.6 in group I, 48.7+/-7.1 in group II and 6.2+/-3.1 in group III (p=0.00002). In conclusion, simvastatin treatment markedly decreased UHMWPE particle-induced osteolysis in a murine calvarial model. This finding suggests that simvastatin may have a role for noninvasive prevention and treatment of wear debris-mediated periprosthetic osteolysis after total joint arthroplasty.

Stimulation of bone formation by zoledronic acid in particle-induced osteolysis.

We investigated the effect of a single subcutaneous dose of zoledronic acid on particle-induced osteolysis and observed excessive regional new bone formation. We utilized the murine calvarial osteolysis model and polyethylene particles in C57BL/J6 mice. Twenty-eight mice were used, seven per group. Specimens were stained with Giemsa dye. The osteoid tissue area was determined. Bone thickness was measured as an indicator of bone growth. Net bone growth was significantly increased in animals with zoledronic acid treatment: 0.02 mm(2)+/-0.03 mm(2) in animals with particle implantation only (group 2), 0.25 mm(2)+/-0.08 mm(2) with particle implantation and zoledronic acid treatment directly after surgery (group 3; p=0.0018), and 0.21 mm(2)+/-0.11 mm(2) with particle implantation and zoledronic acid treatment on the fourth postoperative day (group 4; p=0.0042). The mean bone thickness was 0.2 mm+/-0.04 mm (range 0.17 mm-0.31 mm) in group 1 (sham controls) and 0.16 mm+/-0.02 mm (range 0.14 mm-0.19 mm) in group 2, 0.31 mm+/-0.04 mm (range 0.28 mm-0.39 mm) in group 3, and 0.29 mm+/-0.02 mm (range 0.28 mm-0.34 mm) in group 4. Student's t-test revealed a statistically significant difference between groups 2 and 3 (p=0.00042), and groups 2 and 4 (p=0.0019). In conclusion, our observational study suggests that zoledronic acid may stimulate bone apposition locally in the process of particle-induced osteolysis.

Magnetic Drug Targeting as New Therapeutic Option for the Treatment of Biomaterial Infections.

Implant-associated infections are a challenging problem in surgery. Bacteria in biofilms are difficult to treat as they are less susceptible to antibiotics or antiseptics which require high drug concentrations at the site of infection. We present a novel strategy to concentrate high antibiotic doses systemically at the target site using newly developed antibiotic-functionalized nanoparticles directed by a magnetic drug-targeting system. The important and effective antibiotic gentamicin served as antimicrobial substance and was ionically or covalently attached to magnetic nanoparticles. Subsequently, the particles were characterized thoroughly. Anti-infective properties with regard to Staphylococcus aureus and the degree of cytotoxicity concerning human umbilical vein endothelial cells were determined. The enrichment of the magnetic nanoparticles at the surface of model tubes in circulatory experiments was investigated. We describe a promising technique for the loading of magnetic nanoparticles to treat systemic infections. Gentamicin-coated magnetic nanoparticles reduced bacterial growth even beyond pathologically relevant concentrations within 24 h. Excellent concentration independent biocompatibility was found for the nanoparticles themselves and we demonstrate that the magnetic nanoparticles can be navigated and concentrated on surfaces of model implants using a permanent magnetic field.

Models for the histologic study of the skin interface with percutaneous biomaterials.

Percutaneous devices are critical for health care. Access to tissue, vessels and internal organs afforded by these devices provides the means to treat and monitor many diseases. Unfortunately, such access is not restricted, and infection may compromise the usefulness of the device and even the life of the patient. New biomaterials offer the possibility of maintaining internal access while limiting microbial access, but understanding of the cutaneous/biomaterial interface and models to study this area are limited. This paper focuses on models useful for studying the morphology and biology of the intersection of skin and percutaneous biomaterials. An organ culture and a mouse model are described that offer promising possibilities for improved understanding of this critical interface.