Bedard, Nicholas A.

Background: Infection following extensor mechanism reconstruction (EMR) with Marlex mesh (C.R. Bard) is devastating and limb-threatening. The purpose of this study was to evaluate whether vancomycin-loaded mesh reduces staphylococcal infection in a murine EMR model. Methods: Mouse-sized, 8-layer mesh constructs were fabricated to simulate clinical reconstruction and soaked in a vancomycin solution (50 mg/mL) for in vitro and in vivo testing. Three methicillin-resistant clinical isolates from human periprosthetic Staphylococcus aureus, Staphylococcus epidermidis, and Staphylococcus lugdunensis knee infections were evaluated. In vitro testing assessed vancomycin loading capacity, mechanical properties, antibacterial activity, and inhibition of biofilm formation. For in vivo experiments, plain or vancomycin-loaded mesh was implanted into C57BL/6 mouse extensor mechanisms, which were intraoperatively contaminated with 1 of the 3 study isolates (5 per group). Mesh and surrounding tissue were harvested for quantitative culture on postoperative day 9. Results: For all 3 isolates, vancomycin-loaded mesh produced zones of inhibition and exhibited antibacterial activity through at least 3 days in vitro (p < 0.0001). Mechanical testing revealed that loading mesh with vancomycin did not negatively impact tensile strength, hysteresis, or suture pull-through properties. In vitro testing of inhibition of biofilm formation demonstrated reduced colony-forming units 6 hours after inoculation, which remained low throughout the 9-day experimental period (p < 0.05 for all isolates). In vivo, vancomycin-loaded mesh reduced bacterial burden on mesh and in surrounding tissue by >3 log 10 compared with plain mesh for all 3 isolates (p < 0.01 for both mesh and tissue). Conclusions: Vancomycin-loaded mesh provided in vitro antibacterial activity without compromising mesh mechanical properties and reduced staphylococcal infection in a murine EMR model. Further work is needed to evaluate translational potential and safety before clinical application. Clinical Relevance: Mesh-associated infection after EMR is devastating and difficult to treat. These preclinical findings suggest that local vancomycin delivery may serve as an adjunct to systemic prophylaxis, warranting further study before clinical use.

Background Staphylococcus aureus causes a multiplicity of human diseases acquired in community and healthcare settings alike around the globe. While most studies focus on coding changes to assess genome evolution and study genetic adaptation, interrogation of silent mutations in the form of synonymous codon usage bias is less well-studied. As such, understanding of patterns in codon bias at the gene and genome levels, and how codon bias impacts protein expression in S. aureus remains incomplete. Methods The codon bias of 2,565 protein encoding genes from NCTC 8325 was queried against all publicly available closed S. aureus genomes. Using public BioSample data, genomes were sorted by disease state, submitting institution, and collection site. Codon bias was assessed at the level of gene and genome using the codon adaptation index (CAI), calculated using 30S and 50S ribosomal genes. Gene set enrichment analysis was applied to determine associations between physiological functions, CAI gene scores, and interquartile ranges. CAI scores were also compared to an in vitro S. aureus proteomics database to correlate codon bias and protein expression. Results CAI scores varied within and between isolates at the gene and genome levels. Genes with ribosome-associated functions were most enriched among high CAI genes, and had low CAI interquartile ranges (IQR), suggesting selective pressure to maintain high expression of these genes across all S. aureus isolates. Genome sequences submitted by Aga Khan University Hospital, Nairobi, Kenya were most different from others. For the LAC USA 300 strain, CAI and protein expression were moderately positively correlated (cor = 0.534, p < 2.2e-16). Conclusions Codon bias in S. aureus was shown to vary between gene, and to be a source of genetic variation between isolates; CAI and in vitro protein expression were positively correlated.

Aims Extensor mechanism disruption is a major complication following total knee arthroplasty, with treatment often consisting of extensor mechanism reconstruction utilizing monofilament polypropylene mesh (Marlex mesh, C. R. Bard, Inc). Infection following this procedure is devastating, often resulting in revision surgery and mesh removal, with permanent limb dysfunction. This study evaluated the in vitro ability of vancomycin-loaded polypropylene mesh to inhibit growth of isolates of three Staphylococcus species from patients with periprosthetic joint infection. Methods The mesh was prepared in two configurations – single-layer and eight-layer – and soaked for ten minutes in either sterile water (control) or vancomycin solution (50 mg/ml), after which the mesh was placed on tryptic soy agar plates inoculated with staphylococci and incubated at 37°C for 18 to 24 hours. Zones of inhibition were measured daily over seven days, with mesh transferred to freshly inoculated plates daily. Testing was performed in triplicate, with experiments repeated three times for each bacterial isolate. A total of 30 clinical isolates were tested (five methicillin-susceptible Staphylococcus epidermidis , five methicillin-resistant S. epidermidis , ten methicillin-resistant Staphylococcus aureus , and ten Staphylococcus lugdunensis ). Results Across all species, the eight-layer vancomycin-loaded mesh produced statistically significantly larger median zones of inhibition than the single-layer mesh. The antibacterial activity of the eight-layer mesh persisted through to day 7, while the single-layer mesh showed reduced activity by days 4 to 5. Conclusion Compared with single-layer vancomycin-loaded mesh, multilayer vancomycin-loaded mesh, which mimics clinical application, provides enhanced and sustained antibacterial activity in vitro. Cite this article: Bone Joint Res 2026;15(8):998–1004.

We previously reported 5-year results of 57 patients with major acetabular defects (Paprosky 2B through 3B) who underwent full (31) or half (26) cup-cage reconstructions. This study provides an update with 8.8-year mean follow-up. The 10-year cumulative incidence of and survivorship free from revision, reoperation, and complications were estimated. The 10-year cumulative incidence of revision was 14% for full and 12% for half constructs. The incidence of revision for aseptic loosening was 4.3% and 4.6%, respectively. The 10-year survivorship free from aseptic loosening for patients with pelvic discontinuity was 88.9% (95% confidence interval [CI], 70.6% to 100%) and 85.7% (95% CI, 61.8% to 100%), respectively; no patient without pelvic discontinuity required revision for aseptic loosening. The 10-year cumulative incidence of complications was 42% for all patients, including a 15% incidence of dislocation. Thus, both full and half cup-cage constructs provided durable fixation for complex acetabular bone loss at 10 years, although dislocation remains a concern. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Background: Contemporary rotating-hinge total knee arthroplasties (RH-TKAs) have shown reasonable short-term survivorship in smaller series, but concerns remain regarding risks of aseptic and septic failure. The purpose of this study was to assess outcomes of contemporary RH-TKAs in one of the largest series to date. Methods: We retrospectively identified 575 RH-TKAs (60% used for aseptic etiologies and 40% used during reimplantation in 2-stage treatment of periprosthetic joint infection [PJI]) from 2002 to 2021 at a single institution. The mean age was 67 years, 58% were female, and the mean body mass index was 33 kg/m 2 . Sixty-five percent had Anderson Orthopaedic Research Institute (AORI) type-2B or 3 bone loss. Kaplan-Meier survivorship analyses were performed. The mean follow-up was 6 years (range, 2 to 19 years). Results: Survivorship free from any revision was 76% at 5 years and 64% at 10 years. The most common revision indications were PJI (54%) and aseptic loosening (20%). RH-TKA used in the primary setting showed better survivorship compared with RH-TKA used during reimplantation after PJI (79% versus 60% at 10 years). Survivorship free from revision for aseptic loosening was 96% at 5 years and 90% at 10 years. Survivorship free from revision for PJI was 84% at 5 years and 81% at 10 years. Survivorship free from revision for PJI was even lower for RH-TKAs used during reimplantation, 74% at 5 years and 73% at 10 years. RH-TKA used during reimplantation in the treatment of PJI was associated with an increased risk of any revision (HR = 2, p < 0.001). Radiographic analysis of 425 knees that were not revised and had radiographs available for review showed that 6% of femoral components and 8% of tibial components had evidence of loosening at the time of final follow-up. The mean Knee Society Score improved from 33 to 69 at 2 years (p < 0.001). Conclusions: The 10-year survivorship free from aseptic loosening was 90% in this large series of RH-TKAs. This represents one of the best survivorships free from aseptic loosening published to date. Knees with prior PJI had markedly poorer survivorship than knees treated for aseptic etiologies, with double the risk of revision. Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Aims Total knee arthroplasty (TKA) for end-stage osteonecrosis has historically been associated with concerns regarding aseptic loosening, and long-term data are limited. The purpose of this study was to update and expand our previous series with long-term follow-up, with specific emphasis on implant survivorship, risk factors for failure, complications, and clinical outcomes in a consecutive cohort of TKAs performed for primary and secondary osteonecrosis. Methods We retrospectively identified 295 consecutive TKAs in 266 patients for osteonecrosis performed at a single tertiary care academic institution from January 2002 to July 2022. Of these, 207 TKAs (70%) were performed for primary osteonecrosis, and 88 (30%) for secondary osteonecrosis. The predominant cause of secondary osteonecrosis was steroid use (59%; n = 52), followed by post-traumatic (25%; n = 22), radiation-induced (9%; n = 8), and alcohol-induced (7%; n = 6) osteonecrosis. Implant survivorship was analyzed as a time-to-event outcome using Kaplan-Meier estimation. The mean age was 61 years (18 to 93), with 67% being female (n = 197). The mean follow-up was nine years (2 to 20). Results The 15-year survivorship free of any revision for the entire cohort was 92% (95% CI 87 to 97), with similar rates between primary and secondary osteonecrosis (92% (95% CI 87 to 98) vs 93% (95% CI 87 to 100), respectively; p = 0.459). Varus-valgus constraint implant designs (HR 10.8 (95% CI 2.7 to 43.4); p < 0.001) and tibial stem use (HR 12.0 (95% CI 4.1 to 35.1); p < 0.001) were associated with an increased risk of any revision. The 15-year survivorship free of aseptic loosening was 97% (95% CI 93 to 100) for the entire cohort. Age under 65 years (HR 2.7 (95% CI 1.4 to 5.4); p = 0.005) and secondary osteonecrosis (HR 1.9 (95% CI 1.0 to 3.4); p = 0.044) were associated with an increased risk of any reoperation at 15 years. Conclusion TKA is a durable and reliable option for primary osteonecrosis at long-term follow-up. However, TKAs performed for secondary osteonecrosis carry a higher reoperation risk. Cite this article: Bone Joint J 2026;108-B(4):455–462.

Abstract Background Staphylococcus aureus is a challenging pathogen which causes a multiplicity of human diseases around the globe, acquired in the community and healthcare settings alike. Treatment of S. aureus infection can be challenging and is further compromised by antimicrobial resistance. Understanding of its pathogenesis, transmission pathways and the dynamics of its genome evolution and associated adaptations is incomplete. One strategy to assess genome evolution is to assess codon bias. Historically, studies have focused on the consequences of coding changes; assessing silent mutations in the form of synonymous codon usage bias represents a novel approach to studying genetic adaptation.Figure 1.Principal component analysis (PCA) (A) and sPLS-DA (B) separate S. aureus from complex mates.sPLS-DA component 1 relies on a hypothetical protein, identified here by its NCTC 8325 genomic coordinates, as important for separating S. aureus from complex mates (C). Methods Here, the codon bias of 2,872 genes was queried against all publicly available complete S. aureus plasmids and genomes. Using public BioSample data, genomes were sorted by disease state (e.g., bacteremia, pulmonary infection) and geographical collection site. Results Isolates from Nairobi, Kenya were most different from other isolates, suggesting that geographical isolation may shape codon bias signature. In addition, codon bias of two MSCRAMM proteins implicated in human disease - SdrC and FnBPB - varied between isolation sources, suggesting a role for codon bias in S. aureus genetic adaptation to selective pressures of infection. Additionally, codon bias out-performed coding and nucleic acid mutational metrics in separating members of the S. aureus complex, S. aureus, Staphylococcus argenteus, Staphylococcus schweitzeri, and Staphylococcus roterodami; Fig 1, sparse partial least squares analysis (sPLS-DA) mean AUC codon: 0.89762, nucleic acid: 0.82266, codon bias: 0.9996 (relying on hypothetical protein NC_007795.1:516850-517419). Conclusion This analysis suggests that codon bias in S. aureus is a source of genetic adaptation that can be used to separate strains by geographical isolation source, and separate S. aureus sensu stricto from other S. aureus complex members. Disclosures Nicholas Bedard, MD, Stryker: Advisor/Consultant Robin Patel, MD, a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication, a patent on PET imaging of bacterial infection: a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication, a patent on PET imaging of bacterial infection|MicuRx Pharmaceuticals and bioMérieux: Grant/Research Support|PhAST, Day Zero Diagnostics, DEEPULL DIAGNOSTICS, S.L., Nostics, HealthTrackRx, bioMérieux and CARB-X: Advisor/Consultant|Up-to-Date and the Infectious Diseases Board Review Course: Honoraria

Aims Data on revision of unicompartmental knee arthroplasty (UKA) to total knee arthroplasty (TKA) are limited by low patient numbers and short-term follow-up. This study evaluated the mid-term outcomes of revision of UKA to TKA focusing on implant survival, radiological results, and clinical outcomes in a large series. Methods We identified 235 revisions of UKA to TKA performed between 1995 and 2022 utilizing our institutional total joint registry. The mean age was 65 years (SD 10), mean BMI was 32 kg/m 2 (SD 6), and 50% were female (n = 118). The most common indications for revision were aseptic loosening (37%; n = 83), progression of arthritis in adjacent compartments (35%; n = 81), and unexplained pain (20%; n = 47). The mean time from UKA to revision to a TKA was four years (26 days to 15 years). Posterior-stabilized constructs were used in 78% of the revisions (n = 184), varus-valgus constrained implants in 14% (n = 33), and cruciate-retaining implants in 7% (n = 16). Metaphyseal fixation devices were used in 8% of cases (n = 18) and augments in 31% (n = 73). Kaplan-Meier implant survival analyses were performed, radiographs reviewed, and clinical outcomes were measured with Knee Society Scores (KSSs). Mean follow-up was eight years (2 to 25). Results The five-year survival free of any re-revision was 93% (95% CI 89 to 97). There were 17 further re-revisions with femoral and/or tibial aseptic loosening (n = 7), periprosthetic joint infection (n = 4), and stiffness (n = 2) being the most common indications. The five-year survival free of any reoperation was 87% (95% CI 83 to 92). Stiffness (n = 7) and unresurfaced patellar clunk/crepitus (n = 4) were the most common indications for reoperations without implant exchange. There were 25 nonoperative postoperative complications, most commonly stiffness (n = 5), flexion instability (n = 4), and haematoma (n = 4). No unrevised TKAs showed signs of radiological loosening. KSS function score improved from 54 (SD 18) to 69 (SD 26; p = 0.003). Conclusion In this large series of 235 revisions of UKA to TKA, the five-year survival of the TKAs free of re-revision was good. Our data suggest that the implant survival and clinical outcomes were inferior to primary TKA. Tibial component aseptic loosening was the most common reason for re-revision. Cite this article: Bone Joint J 2025;107-B(12):1281–1287.

Background: Although patients often aim to lose weight after total hip arthroplasty (THA) or total knee arthroplasty (TKA), long-term changes in body mass index (BMI) are unknown. We analyzed BMI at 2, 5, and 10 years after primary THA and TKA and determined predictors of BMI change. Methods: We identified patients who underwent primary THA or TKA for osteoarthritis between 2001 and 2011 and had a BMI at surgery and at 2, 5, and 10 years postoperatively. This resulted in 763 patients (310 who underwent THA and 453 who underwent TKA). The mean patient age was 66 years, and 60% of patients were female. BMI changes were analyzed with repeated-measures analysis of variance. Multinomial logistic regression determined predictors of BMI change. Results: Following THA, the mean BMI increased from 30.3 kg/m 2 at surgery to 30.9 kg/m 2 at both 2 years (p = 0.003) and 5 years (p = 0.002). Following TKA, the mean BMI increased from 32.7 kg/m 2 at surgery to 33.1 kg/m 2 at both 2 years (p = 0.053) and 5 years (p = 0.040). By 10 years, the mean BMI was 30.6 kg/m 2 (p = 0.453) for patients undergoing THA and 32.6 kg/m 2 (p = 0.947) for patients undergoing TKA, similar to the BMIs at surgery. At 10 years, 27% of patients who underwent THA and 30% of patients who underwent TKA had a BMI decrease of >5%, whereas 30% of patients who underwent THA and 32% of patients who underwent TKA had a BMI increase of >5%. Female sex among patients who underwent THA increased the odds of a >5% BMI increase at 10 years (odds ratio [OR], 2.1; p = 0.006). Older age among patients who underwent TKA decreased the odds of a >5% BMI increase at 10 years (OR per year, 0.95; p < 0.001). Conclusions: Although most patients experienced a BMI change of >5% at 10 years, the mean BMI did not meaningfully change 2, 5, or 10 years after THA or TKA. Arthroplasty should not be viewed as a gateway to BMI improvement for patients overall, but female sex and older age may predict clinically important weight changes 10 years after arthroplasty. Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

ABSTRACT Periprosthetic joint infection (PJI) is the most common and difficult to treat form of arthroplasty failure. While treatment with debridement, antibiotics, and implant retention (DAIR) is preferable to one- or two-stage implant exchange based on morbidity and cost, outcomes are not successful in all cases selected for this management strategy. DAIR is currently recommended when infection is perceived to be in an “acute” phase, based on symptom duration; despite this selection strategy, DAIR failure rates are high. A more objective means of predicting DAIR success could improve patient outcomes by limiting DAIR failures. To explore this possibility, advanced proteomic analysis of sonicate fluid samples from 95 subjects with PJI was performed using proximity extension assay (PEA), with 77 samples additionally undergoing complementary proteomics analysis with liquid chromatography with tandem mass spectrometry (LC-MS/MS). Sparse partial least squares differentiation analysis (sPLS-DA) separated samples from patients who underwent DAIR with known outcomes ( n = 19) into successful or unsuccessful groups, predicting DAIR surgical outcome (area under the curve [AUC]: 1; mean “leave one out” AUC: 0.6). Proteins predictive of DAIR surgical outcome were significantly enriched for the “protein repair” Gene Ontology (GO) pathway ( P -adj = 0.02). Additionally, proteomic signatures associated with symptom duration in PJI categorized samples into short and long symptom duration PJI. In summary, an investigation of 7,261 unique human proteins separated PJI-associated samples based on symptom duration and identified a proteomic profile predictive of DAIR success. IMPORTANCE Chronic infections are generally understood to last months to years, with acute infections lasting days to weeks. The transition from acute to chronic infection is, however, poorly understood. Periprosthetic joint infection (PJI) has been considered more challenging to treat when “chronic” than when “acute.” A surgery preferred for its recovery time and cost—debridement, antibiotics, and implant retention (DAIR)—is recommended for PJI management when symptom duration is short; yet, even in this select patient group, DAIR is associated with a high treatment failure rate. A means to better identify those predicted to have a successful outcome if they undergo DAIR is needed. Here, over 7,000 proteins from human clinical PJI samples were measured and shown to be able to separate samples based on symptom duration. Importantly, a proteomic profile predictive of DAIR success was identified.