Staphylococcus aureus (S. 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. Pro-inflammatory signals induce MDSC recruitment and activation in tumor models; however, the mechanisms responsible for MDSC homing to sites of biofilm infection are unknown. Here 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 KO mice, which resulted in enhanced monocyte and neutrophil influx and bacterial clearance. Adoptive transfer of wild type MDSCs into infected p40 KO 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.

Background Rotational malalignment of total knee arthroplasty (TKA) has been correlated with patellofemoral maltracking, knee instability, and stiffness. CT is the most accurate method to assess rotational alignment of prosthetic components after TKA, but inter-and intraobserver reliability of CT scans for this use has not been well documented. Questions/purposes The objective of this study was to determine the inter-and intraobserver reliability and the repeatability of the measurement of TKA component rotation using two-dimensional CT scans. Methods Fifty-two CT scans of TKAs being evaluated for revision surgery were measured by three different physicians. An orthopaedic resident and attending measured the same scans twice (more than 2 weeks apart) and a musculoskeletal radiologist measured them once. To assess interobserver reliability, intraclass correlation coefficients (ICCs) with two-way mixed-effects analysis of variance models as well as 95% confidence intervals for each were done. The repeatability coefficient was calculated as well, which is defined as the difference in measurements that include 95% of the values. This indicates the magnitude of variability among measurements in the same scale, which in this study is degrees. Results The interobserver ICC measurement for the femoral component was 0.386 (poor), and it was 0.670 (good) for the tibial component. The interobserver ICC for the combined rotation measurements was 0.617 (good). The intraobserver ICC for the femoral component was 0.606 (good), and it was 0.809 (very good) for the tibial component. The intraobserver ICC for combined rotation was 0.751 (good). The intraobserver repeatability coefficient for the femoral component was 0.49°, 10.64°for the tibial component, and 12.29°for combined rotation. Conclusions In this study, the inter-and intraobserver reliability, and the repeatability, of TKA component rotation were variable. This raises concern about whether CT scan is diagnostic in the assessment of component malrotation after TKA.

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.

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.

Oxidized zirconium, a material with a ceramic surface on a metal substrate, and highly cross-linked polyethylene are two materials developed to reduce wear. We measured in vivo femoral head penetration in patients with these advanced bearings. We hypothesized the linear wear rates would be lower than those published for cobaltchrome and standard polyethylene. We retrospectively reviewed a select series of 56 THAs in a relatively young, active patient population utilizing oxidized zirconium femoral heads and highly cross-linked polyethylene acetabular liners. Femoral head penetration was determined using the Martell computerized edge-detection method. All patients were available for 2-year clinical and radiographic followup. True linear wear was 4 lm/year (95% confidence intervals, ± 59 lm/year). The early wear rates in this cohort of relatively young, active patients were low and we believe justify the continued study of these alternative bearing surfaces.