Metaphyseal Fixation Using Cones and Sleeves for Severe Proximal Tibial Bone Loss.

BACKGROUND: Tibial bone defects are commonly encountered in revision total knee arthroplasty (rTKA) and can be managed with metaphyseal cones or sleeves. Few studies have directly compared tibial cones and sleeves in rTKA, and none have limited this comparison to the most severe tibial defects. The purpose of this study was to evaluate and compare the outcomes of metaphyseal cones and sleeves for tibial reconstruction in rTKA regarding implant fixation and clinical outcomes. METHODS: A retrospective review was conducted on patients undergoing rTKA in which metaphyseal cones or sleeves were utilized for addressing metaphyseal bone loss (34 cones and 18 sleeves). Tibial bone loss was classified according to the Anderson Orthopaedic Research Institute bone defect classification, with types 2B and 3 being included. Patient-reported outcomes and postoperative complications were collected, and a radiographic evaluation of osseointegration or loosening was performed. RESULTS: There were 52 knees included (34 cones, 18 sleeves), with a median follow-up of 41.0 months. All-cause implant survival was 100% at 2 years and 96% (95% confidence interval: 76 to 99%) at 4 years, with 98% of tibial components demonstrating osseointegration at the final follow-up. During follow-up, there were a total 11 revisions, of which 1 sleeve was revised secondary to implant loosening. Tibial sleeves had a higher risk of revision compared to tibial cones (P < .01), and sleeves fixed with a hybrid technique were more likely to need revision than cones fixed by the same method (P = .01). CONCLUSIONS: Porous metaphyseal tibial cones and tibial metaphyseal sleeves both performed well at a 41-month median follow-up with no difference in aseptic survivorship between the 2 constructs. Both demonstrate high rates of osseointegration, low rates of aseptic failure, and significant improvement in Knee Society Scores in patients with severe tibial defects in rTKA.

Novel Technique for the Identification of Hip Implants Using Artificial Intelligence.

BACKGROUND: The anticipated growth of total hip arthroplasty will result in an increased need for revision total hip arthroplasty. Preoperative planning, including identifying current implants, is critical for successful revision surgery. Artificial intelligence (AI) is promising for aiding clinical decision-making, including hip implant identification. However, previous studies have limitations such as small datasets, dissimilar stem designs, limited scalability, and the need for AI expertise. To address these limitations, we developed a novel technique to generate large datasets, tested radiographically similar stems, and demonstrated scalability utilizing a no-code machine learning solution. METHODS: We trained, validated, and tested an automated machine learning-implemented convolutional neural network to classify 9 radiographically similar femoral implants with a metaphyseal-fitting wedge taper design. Our novel technique uses computed tomography-derived projections of a 3-dimensional scanned implant model superimposed within a computed tomography pelvis volume. We employed computer-aided design modeling and MATLAB to process and manipulate the images. This generated 27,020 images for training (22,957) and validation (4,063) sets. We obtained 786 test images from various sources. The performance of the model was evaluated by calculating sensitivity, specificity, and accuracy. RESULTS: Our machine learning model discriminated the 9 implant models with a mean accuracy of 97.4%, sensitivity of 88.4%, and specificity of 98.5%. CONCLUSIONS: Our novel hip implant detection technique accurately identified 9 radiographically similar implants. The method generates large datasets, is scalable, and can include historic or obscure implants. The no-code machine learning model demonstrates the feasibility of obtaining meaningful results without AI expertise, encouraging further research in this area.

Granulocytic myeloid-derived suppressor cell activity during biofilm infection is regulated by a glycolysis/HIF1a axis.

Staphylococcus aureus is a leading cause of biofilm-associated prosthetic joint infection (PJI). A primary contributor to infection chronicity is an expansion of granulocytic myeloid-derived suppressor cells (G-MDSCs), which are critical for orchestrating the antiinflammatory biofilm milieu. Single-cell sequencing and bioinformatic metabolic algorithms were used to explore the link between G-MDSC metabolism and S. aureus PJI outcome. Glycolysis and the hypoxia response through HIF1a were significantly enriched in G-MDSCs. Interfering with both pathways in vivo, using a 2-deoxyglucose nanopreparation and granulocyte-targeted Hif1a conditional KO mice, respectively, attenuated G-MDSC-mediated immunosuppression and reduced bacterial burden in a mouse model of S. aureus PJI. In addition, single-cell RNA-Seq (scRNA-Seq) analysis of granulocytes from PJI patients also showed an enrichment in glycolysis and hypoxia-response genes. These findings support the importance of a glycolysis/HIF1a axis in promoting G-MDSC antiinflammatory activity and biofilm persistence during PJI.

The Challenge of Emerging Resistant Gram-Positive Pathogens in Hip and Knee Periprosthetic Joint Infections.

➤: An increase in resistant bacterial pathogens has occurred over the last 4 decades. ➤: Careful patient selection and improving or correcting risk factors for periprosthetic joint infection (PJI) before elective surgical treatment are strongly recommended. ➤: Appropriate microbiological methods, including those used to detect and grow Cutibacterium acnes, are recommended. ➤: Antimicrobial agents used in the prevention or management of infection should be selected appropriately and the duration of therapy should be carefully considered in order to mitigate the risk of developing bacterial resistance. ➤: Molecular methods including rapid polymerase chain reaction (PCR) diagnostics, 16S sequencing, and/or shotgun and/or targeted whole-genome sequencing are recommended in culture-negative cases of PJI. ➤: Expert consultation with an infectious diseases specialist (if available) is recommended to assist with the appropriate antimicrobial management and monitoring of patients with PJI.

Increased Incidence of Methicillin-Resistant Staphylococcus aureus in Knee and Hip Prosthetic Joint Infection.

BACKGROUND: Periprosthetic joint infection (PJI) is a devastating complication of knee and hip arthroplasty. Past literature has shown that gram-positive bacteria are commonly responsible for these infections, although limited research exists studying the changes in the microbial profile of PJIs over time. This study sought to analyze the incidence and trends of pathogens responsible for PJI over three decades. METHODS: This is a multi-institutional retrospective review of patients who had a knee or hip PJI from 1990 to 2020. Patients with a known causative organism were included and those with insufficient culture sensitivity data were excluded. There were 731 eligible joint infections from 715 patients identified. Organisms were divided into multiple categories based on genus/species and 5-year increments were used to analyze the study period. The Cochran-Armitage trend tests were used to evaluate linear trends in microbial profile over time and a P-value <.05 was considered statistically significant. RESULTS: There was a statistically significant positive linear trend in the incidence of methicillin-resistant Staphylococcus aureus over time (P = .0088) as well as a statistically significant negative linear trend in the incidence of coagulase-negative staphylococci over time (P = .0018). There was no statistical significance between organism and affected joint (knee/hip). CONCLUSION: The incidence of methicillin-resistant Staphylococcus aureus PJI is increasing over time, whereas, coagulase-negative staphylococci PJI is decreasing, paralleling the global trend of antibiotic resistance. Identifying these trends may help with the prevention and treatment of PJI through methods such as remodeling perioperative protocols, modifying prophylactic/empiric antimicrobial approaches, or transitioning to alternative therapeutic strategies.

Total Joint Arthroplasty in Patients With an Implanted Left Ventricular Assist Device.

Left ventricular assist devices (LVADs) may be used as bridge therapy or destination therapy in heart failure patients. Total joint arthroplasty may improve the functional status of patients limited by arthritis. This retrospective case series evaluated patients with an implanted LVAD who underwent a total joint arthroplasty at 1 institution from 2012 to present. Five patients underwent 12 surgeries with 7 primary arthroplasties and 5 revisions. Their mortality, length of stay, coagulopathic events, incidence of infection or revision arthroplasty, and heart transplantation were evaluated, and is the largest study to date of this population. Two patients expired from thrombotic events while 3 progressed to heart transplantation. Joint arthroplasty is feasible in patients with an implanted LVAD with expected risk and perioperative multidisciplinary collaboration.

Predictors of Reinfection in Prosthetic Joint Infections Following Two-Stage Reimplantation.

BACKGROUND: Two-stage reimplantation is an effective treatment for periprosthetic joint infection (PJI). Many factors are involved in the variable success of this procedure. The purpose of this study is to examine the relationship between patient risk factors, comorbidities, and the pathogen on reinfection rates following two-stage reimplantation. METHODS: We evaluated 158 patients treated for PJI from 2008-2019. Only patients who had completed a two-stage exchange were included. Patient demographics, comorbidities, laboratory values, time-to-reimplantation, pathogen, antibiotic sensitivities, host status, and reinfection rates were assessed. Multivariate analysis was performed to identify correlation between risk factors and reinfection. A P-value < .05 was considered statistically significant. RESULTS: 31 patients experienced a reinfection (19.6%). There was a statistically significant association between infection with Methicillin Sensitive Staphylococcus Aureus (MSSA) and reinfection (P = .046). Patients with a reinfection also had a significantly greater median serum C-reactive protein (CRP) level (12.65 g/dL) at the time of diagnosis compared to patients without a reinfection (5.0 g/dL) (P = .010). Median Erythrocyte Sedimentation Rate (ESR) (56 in no re-infection and 69 in re-infection) and time-to-reimplantation (101 days in no reinfection and 141 days in reinfection) demonstrated a trend toward an association with re-infection but were not statistically significant (P = .055 and P = .054 respectively). CONCLUSION: As the number of arthroplasties continue to rise, PJIs are increasing proportionately and represent a significant revision burden. Elevated C-reactive protein (CRP) levels and Methicillin Sensitive Staphylococcus aureus (MSSA) infection were strongly associated with failure of a two-stage reimplantation. While not statistically significant with our numbers, there were strong trends toward an association between elevated Erythrocyte Sedimentation Rate (ESR), longer time-to-reimplantation, and reinfection.

Pain associated with cemented and uncemented long-stemmed tibial components in revision total knee arthroplasty.

AIMS: Stemmed tibial components are frequently used in revision total knee arthroplasty (TKA). The purpose of this study was to evaluate patient satisfaction, overall pain, and diaphyseal tibial pain in patients who underwent revision TKA with cemented or uncemented stemmed tibial components. METHODS: This is a retrospective cohort study involving 110 patients with revision TKA with cemented versus uncemented stemmed tibial components. Patients who underwent revision TKA with stemmed tibial components over a 15-year period at a single institution with at least two-year follow-up were assessed. Pain was evaluated through postal surveys. There were 63 patients with cemented tibial stems and 47 with uncemented stems. Radiographs and Knee Society Scores were used to evaluate for objective findings associated with pain or patient dissatisfaction. Postal surveys were analyzed using Fisher's exact test and the independent-samples t-test. Logistic regression was used to adjust for age, sex, and preoperative bone loss. RESULTS: No statistically significant differences in stem length, operative side, or indications for revision were found between the two cohorts. Tibial pain at the end of the stem was present in 25.3% (16/63) of cemented stems and 25.5% (12/47) of uncemented stems (p = 1.000); 74.6% (47/63) of cemented patients and 78.7% (37/47) of uncemented patients were satisfied following revision TKA (p = 0.657). CONCLUSION: There were no differences in patient satisfaction, overall pain, and diaphyseal tibial pain in cemented and uncemented stemmed tibial components in revision TKA. Patient factors, rather than implant selection and surgical technique, likely play a large role in the presence of postoperative pain. Stemmed tibial components have been shown to be a possible source of pain in revision TKA. There is no difference in patient satisfaction or postoperative pain with cemented or uncemented stemmed tibial components in revision TKA. Cite this article: Bone Joint J 2021;103-B(6 Supple A):165-170.

Orthopaedic Surgery Elicits a Systemic Anti-Inflammatory Signature.

Little information is available on the functional activity of leukocytes after arthroplasty or the expansion of populations with immune suppressive properties during the acute post-operative period. Synovial fluid and matched pre- and post-surgical blood samples were collected from total hip and knee arthroplasty patients (THA and TKA, respectively) to examine the impact of surgery on peripheral blood leukocyte frequency, bactericidal activity, and inflammatory mediator expression. For spinal surgeries, inflammatory mediator production by peripheral blood mononuclear cells (PBMCs) pre- and post-surgery was examined. An expansion of immune suppressive granulocytic myeloid-derived suppressor cells (G-MDSCs) was observed following arthroplasty, which correlated with significantly increased serum interleukin-10 (IL-10) levels. Analysis of synovial fluid from THA and TKAs revealed reduced granulocyte colony-stimulating factor (G-CSF) and soluble CD40 ligand (sCD40L) and increased interleukin-6 (IL-6), monocyte chemoattractant protein 2 (CCL2) and Fms-like tyrosine kinase 3 ligand (Flt-3L) compared to pre- and post-surgical serum. For the spinal surgery cohort, stimulation of PBMCs isolated post-surgery with bacterial antigens produced significantly less pro-inflammatory (IL-1α, IL-1ß, interleukin-1 receptor antagonist (IL-1RA), IL-12p40, growth-related oncogene-α/GRO-α (CXCL1) and 6Ckine (CCL21)) and more anti-inflammatory/tissue repair mediators (IL-10, G-CSF and granulocyte-macrophage colony-stimulating factor (GM-CSF)) compared to PBMCs recovered before surgery. The observed bias towards systemic anti-inflammatory changes without concomitant increases in pro-inflammatory responses may influence susceptibility to infection following orthopaedic surgery in the context of underlying co-morbidities or risk factors.

2020 Mark Coventry Award: Microorganism-directed oral antibiotics reduce the rate of failure due to further infection after two-stage revision hip or knee arthroplasty for chronic infection: a multicentre randomized controlled trial at a minimum of two years.

AIMS: The aim of this study was to determine if a three-month course of microorganism-directed oral antibiotics reduces the rate of failure due to further infection following two-stage revision for chronic prosthetic joint infection (PJI) of the hip and knee. METHODS: A total of 185 patients undergoing a two-stage revision in seven different centres were prospectively enrolled. Of these patients, 93 were randomized to receive microorganism-directed oral antibiotics for three months following reimplantation; 88 were randomized to receive no antibiotics, and four were withdrawn before randomization. Of the 181 randomized patients, 28 were lost to follow-up, six died before two years follow-up, and five with culture negative infections were excluded. The remaining 142 patients were followed for a mean of 3.3 years (2.0 to 7.6) with failure due to a further infection as the primary endpoint. Patients who were treated with antibiotics were also assessed for their adherence to the medication regime and for side effects to antibiotics. RESULTS: Nine of 72 patients (12.5%) who received antibiotics failed due to further infection compared with 20 of 70 patients (28.6%) who did not receive antibiotics (p = 0.012). Five patients (6.9%) in the treatment group experienced adverse effects related to the administered antibiotics severe enough to warrant discontinuation. CONCLUSION: This multicentre randomized controlled trial showed that a three-month course of microorganism-directed, oral antibiotics significantly reduced the rate of failure due to further infection following a two-stage revision of total hip or knee arthroplasty for chronic PJI. Cite this article: Bone Joint J 2020;102-B(6 Supple A):3-9.

Impact of Chronic Kidney Disease in Older Adults Undergoing Hip or Knee Arthroplasty: A Large Database Study.

BACKGROUND: Hip and knee arthroplasties are among the most commonly performed surgical procedures in the elderly. In this age group, uncertainty exists regarding the importance of mild to moderate chronic kidney disease (CKD), which is prevalent but often unrecognized in the perioperative setting. This study evaluates the association between mild to moderate CKD and adverse postoperative outcomes in patients 65 years or older METHODS: This retrospective study selected patients 65 years or older undergoing hip or knee arthroplasty between 2006 and 2016 from the National Surgical Quality Improvement Program database. We created logistic regression models to analyze the relationship between CKD stage and each of our coprimary outcomes. The primary outcomes were major complication and mortality occurring within 30 days of surgery. RESULTS: Of the 193,747 included patients, 68,424 (35.3%) underwent hip and 125,323 (64.7%) knee arthroplasty. Within 30 days of surgery, 12,767 patients (6.6%) experienced a major complication and 352 (0.2%) died. Compared to patients with no kidney disease, patients with CKD stages 3b and 4 were at higher risk for both major complication (adjusted odds ratio [aOR] 1.28 [1.08-1.52], aOR 1.5 [1.13-1.98], respectively) and mortality (aOR 3.17 [1.23-8.14], aOR 3.93 [1.26-12.21], respectively) after hip arthroplasty, and for major complication (aOR 1.42 [1.23-1.63], aOR 1.52 [1.19-1.93], respectively) after knee arthroplasty. CONCLUSION: Among elderly patients, stage 3b and stage 4 CKD were associated with 30-day postoperative major complication after hip or knee arthroplasty, and with 30-day postoperative mortality after hip, but not knee, arthroplasty. Further research will be required to inform perioperative management decisions.

Surface nano-modification by ion beam-assisted deposition alters the expression of osteogenic genes in osteoblasts.

Biomaterials with enhanced biocompatibility are favored in implant studies to improve the outcomes of total joint replacement surgeries. This study tested the hypothesis that nano-structured surfaces for orthopedic applications, produced by the ion beam-assisted deposition method, would enhance osteointegration by altering the expression of bone-associated genes in osteoblasts. The ion beam-assisted deposition technique was employed to deposit nano-films on glass or titanium substrates. The effects of the ion beam-assisted deposition produced surfaces on the human osteosarcoma cell line SAOS-2 at the molecular level were investigated by assays of adhesion, proliferation, differentiation, and apoptosis on coated surfaces versus uncoated cobalt-chrome, as the control. Ion beam-assisted deposition nano-coatings enhanced bone-associated gene expression at initial cell adhesion, proliferation, and differentiation compared to cobalt-chrome surfaces as assessed by polymerase chain reaction techniques. Increased cell proliferation was observed using a nuclear cell proliferation-associated antigen. Moreover, enhanced cell differentiation was determined by alkaline phosphatase activity, an indicator of bone formation. In addition, programmed cell death assessed by annexin V staining and flow cytometry was lower on nano-surfaces compared to cobalt-chrome surfaces. Overall, the results indicate that nano-coated surfaces produced by the ion beam-assisted deposition technique for use on implants were superior to orthopedic grade cobalt-chrome in supporting bone cell adhesion, proliferation, and differentiation and reducing apoptosis. Thus, surface properties altered by the ion beam-assisted deposition technique should enhance bone formation and increase the biocompatibility of bone cell-associated surfaces.

Bone-targeting liposome formulation of Salvianic acid A accelerates the healing of delayed fracture Union in Mice.

Delayed fracture union is a significant clinical challenge in orthopedic practice. There are few non-surgical therapeutic options for this pathology. To address this challenge, we have developed a bone-targeting liposome (BTL) formulation of salvianic acid A (SAA), a potent bone anabolic agent, for improved treatment of delayed fracture union. Using pyrophosphorylated cholesterol as the targeting ligand, the liposome formulation (SAA-BTL) has demonstrated strong affinity to hydroxyapatite in vitro, and to bones in vivo. Locally administered SAA-BTL was found to significantly improve fracture callus formation and micro-architecture with accelerated mineralization rate in callus when compared to the dose equivalent SAA, non-targeting SAA liposome (SAA-NTL) or no treatment on a prednisone-induced delayed fracture union mouse model. Biomechanical analyses further validated the potent therapeutic efficacy of SAA-BTL. These results support SAA-BTL formulation, as a promising therapeutic candidate, to be further developed into an effective and safe clinical treatment for delayed bone fracture union.

Human prosthetic joint infections are associated with myeloid-derived suppressor cells (MDSCs): Implications for infection persistence.

Prosthetic joint infection (PJI) is a devastating complication of joint arthroplasty surgery typified by biofilm formation. Currently, mechanisms whereby biofilms persist and evade immune-mediated clearance in immune competent patients remain largely ill-defined. Therefore, the current study characterized leukocyte infiltrates and inflammatory mediator expression in tissues from patients with PJI compared to aseptic loosening. CD33+ HLA-DR- CD66b+ CD14-/low granulocytic myeloid-derived suppressor cells (G-MDSCs) were the predominant leukocyte population at sites of human PJI compared to aseptic tissues. MDSCs inhibit T cell proliferation, which coincided with reduced T cells in PJIs compared to aseptic tissues. IL-10, IL-6, and CXCL1 were significantly elevated in PJI tissues and have been implicated in MDSC inhibitory activity, expansion, and recruitment, respectively, which may account for their preferential increase in PJIs. This bias towards G-MDSC accumulation during human PJI could account for the chronicity of these infections by preventing the pro-inflammatory, antimicrobial actions of immune effector cells. CLINICAL SIGNIFICANCE: Animal models of PJI have revealed a critical role for MDSCs and IL-10 in promoting infection persistence; however, whether this population is prevalent during human PJI and across distinct bacterial pathogens remains unknown. This study has identified that granulocytic-MDSC infiltrates are unique to human PJIs caused by distinct bacteria, which are not associated with aseptic loosening of prosthetic joints. Better defining the immune status of human PJIs could lead to novel immune-mediated approaches to facilitate PJI clearance in combination with conventional antibiotics. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1605-1613, 2018.

Low wear rates seen in THAs with highly crosslinked polyethylene at 9 to 14 years in patients younger than age 50 years.

BACKGROUND: Patients 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/PURPOSES: The 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? METHODS: From 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/m(2) (range, 17-51 kg/m(2)).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. RESULTS: The 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 mm(3)/year (95% CI, 4-14 mm(3)/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). CONCLUSIONS: In 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 EVIDENCE: Level III, therapeutic study.

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

OBJECTIVE: To assess and compare the impact of total knee arthroplasty (TKA) in patients with rheumatoid arthritis (RA) and patients with osteoarthritis (OA). METHODS: Patients with rheumatologist-diagnosed arthritis undergoing primary TKA during 1999-2012 were identified. Indices of pain (overall, index knee, and contralateral knee) and health-related quality of life (HRQOL) were obtained in 3 consecutive 6-month intervals: preoperative (baseline), perioperative, and postoperative (recovery). Descriptive statistics and one-way analysis of variance were used to compare TKA outcomes by diagnosis. Effect sizes and standardized response means (SRMs) were calculated between baseline and recovery. RESULTS: Of the participating 18,897 patients, 834 of those with RA (5.3%) and 315 of those with OA (10.2%) had undergone index TKA at similar mean ages (65 and 68 years). Post-TKA, significant improvements were observed for most domains of pain, function, and HRQOL within both disease groups, with greater impact in OA. Based on the SRM, the maximum improvement was shown in index knee pain (SRM -1.33 in RA and -1.34 in OA; effect size -1.75 and -1.94, respectively). The Health Assessment Questionnaire II and the Short Form 36 physical component summary were the most responsive HRQOL indices in detecting post-TKA improvement in RA. A diagnosis of RA, lower income, and preoperative anxiety were independently associated with a lower degree of improvement in index knee pain following TKA. CONCLUSION: TKA is highly effective in reducing clinically relevant knee pain (to a greater extent than its effect on other subjective HRQOL indices in patients with RA), although this improvement is less marked as compared to that among patients with OA. TKA serves as a "time machine" via which patients can return to a lifestyle with less disability, before the arthritis process catches up in RA.

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-1ß, 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.

Current and future trends in the diagnosis of periprosthetic hip infection.

The challenge of confirming the diagnosis of prosthetic hip infection is two-fold. First, the presentation of the patient with a prosthetic hip infection often has limited or few subjective complaints and physical findings, nonconfirmatory inflammatory laboratory markers, and negative culture results. Second, there has not been consistent agreement of the definition of prosthetic join infection. Recent work by the Musculoskeletal Infection Society has created a new uniform definition for research and clinical use that may improve the ability to accurately diagnose prosthetic hip infections individually and share data among different sites for research collaboration.