Understanding Infection: A Primer on Animal Models of Periprosthetic Joint Infection

Periprosthetic joint infections are devastating complications for patients and for our health system. With growing demand for arthroplasty, the incidence of these infections is projected to increase exponentially. This paper is a review of existing animal models to study periprosthetic infection aimed at providing scientists with a succinct presentation of strengths and weaknesses of available in vivo systems. These systems represent the tools available to investigate novel antimicrobial therapies and reduce the clinical and economic impact of implant infections

MELD score predicts short-term outcomes after surgical management of proximal humerus fractures: a matched analysis

ObjectiveWe aimed to evaluate the difference in 30-day outcomes after surgical management of proximal humerus fractures (PHFs) between patients with and without chronic liver disease as defined by a MELD score greater than 10.DesignThis was a retrospective database review.SettingAll centers participating in the American College of Surgeons National Surgical Quality Improvement Program database were included.Patients/participantsPatients with proximal humerus fractures who (1) underwent ORIF, HA, or SA and (2) had calculable MELD scores were included.InterventionOpen reduction and internal fixation, hemiarthroplasty, or shoulder arthroplasty was used for treatment.Main outcome measurementsThirty-day complications, mortality, readmission, and reoperation rates were measured.ResultsOf the total 1732 PHF patients identified, 300 had a MELD score higher than 10. After propensity matching by significant covariates, MELD score higher than 10 was found to be significantly associated with higher rates of 30-day mortality, 30-day readmission, transfusion within 72 hours, and systemic complications. Among patients with a MELD score higher than 10, treatment with SA or HA instead of ORIF was associated with a higher rate of transfusion and longer operative time. There were no significant differences between treatment cohorts regarding mortality, reoperation, readmission, or complications.ConclusionsA MELD score higher than 10 is associated with higher risk of surgical complications, transfusion, and death in patients undergoing surgery for proximal humerus fractures. Among patients with a MELD score higher than 10, ORIF was associated with a lower transfusion rate and shorter operative time than arthroplasty or hemiarthroplasty.Level of evidencePrognostic Level III

Revision total knee arthroplasty outcomes in solid organ transplant Patients, a matched cohort study of aseptic and infected revisions

Background: Previous studies have demonstrated that solid organ transplant (SOT) patients undergoing primary total knee arthroplasty (TKA) are at an increased risk of postoperative complications. The purpose of this study is to utilize a large, national database to investigate revision TKA (rTKA) outcomes in SOT patients. Methods: This was a retrospective review utilizing the Nationwide Readmissions Database (NRD) and ICD-9 codes to identify patients who underwent rTKA from 2010-2014 with a history of at least one SOT. Propensity-score-matching (PSM) was used to compare rTKA outcomes in SOT patients compared to matched patients without SOT. Results: A total of 303,867 rTKAs, with 464 of those being performed in SOT patients, were included in the study. Of these, 71,903 and 182 were performed for PJI in non-SOT and SOT patients, respectively. rTKA was performed most frequently in kidney transplant patients (53.0%) followed by liver transplant patients (34.3%). For non-PJI patients, SOT patients had a higher 90-day readmission rate than matched non-SOT rTKA patients (23.2% vs 12.6%, p = 0.006). However, there were no differences in 90-day readmission rates for specific rTKA complications, subsequent revision rTKA, or mortality. Among patients undergoing rTKA for PJI, there was no difference in overall 90-day readmission rate, readmission for specific rTKA complications, subsequent revision rTKA, or mortality. Conclusions: While the increased medical comorbidities associated with SOT place patients at increased risk for complications following rTKA, it appears that SOT alone does not do so when patients are matched based on overall medical comorbidity

A Mouse Model of Post-Arthroplasty Staphylococcus aureus Joint Infection to Evaluate In Vivo the Efficacy of Antimicrobial Implant Coatings

Post-arthroplasty infections represent a devastating complication of total joint replacement surgery, resulting in multiple reoperations, prolonged antibiotic use, extended disability and worse clinical outcomes. As the number of arthroplasties in the U.S. will exceed 3.8 million surgeries per year by 2030, the number of post-arthroplasty infections is projected to increase to over 266,000 infections annually. The treatment of these infections will exhaust healthcare resources and dramatically increase medical costs.To evaluate novel preventative therapeutic strategies against post-arthroplasty infections, a mouse model was developed in which a bioluminescent Staphylococcus aureus strain was inoculated into a knee joint containing an orthopaedic implant and advanced in vivo imaging was used to measure the bacterial burden in real-time. Mice inoculated with 5x10(3) and 5x10(4) CFUs developed increased bacterial counts with marked swelling of the affected leg, consistent with an acute joint infection. In contrast, mice inoculated with 5x10(2) CFUs developed a low-grade infection, resembling a more chronic infection. Ex vivo bacterial counts highly correlated with in vivo bioluminescence signals and EGFP-neutrophil fluorescence of LysEGFP mice was used to measure the infection-induced inflammation. Furthermore, biofilm formation on the implants was visualized at 7 and 14 postoperative days by variable-pressure scanning electron microscopy (VP-SEM). Using this model, a minocycline/rifampin-impregnated bioresorbable polymer implant coating was effective in reducing the infection, decreasing inflammation and preventing biofilm formation.Taken together, this mouse model may represent an alternative pre-clinical screening tool to evaluate novel in vivo therapeutic strategies before studies in larger animals and in human subjects. Furthermore, the antibiotic-polymer implant coating evaluated in this study was clinically effective, suggesting the potential for this strategy as a therapeutic intervention to combat post-arthroplasty infections

Protective role of IL-1β against post-arthroplasty Staphylococcus aureus infection

MyD88 is an adapter molecule that is used by both IL-1R and TLR family members to initiate downstream signaling and promote immune responses. Given that IL-1β is induced after Staphylococcus aureus infections and TLR2 is activated by S. aureus lipopeptides, we hypothesized that IL-1β and TLR2 contribute to MyD88-dependent protective immune responses against post-arthroplasty S. aureus infections. To test this hypothesis, we used a mouse model of a post-arthroplasty S. aureus infection to compare the bacterial burden, biofilm formation and neutrophil recruitment in IL-1β-deficient, TLR2-deficient and wild-type (wt) mice. By using in vivo bioluminescence imaging, we found that the bacterial burden in IL-1β-deficient mice was 26-fold higher at 1 day after infection and remained 3- to 10-fold greater than wt mice through day 42. In contrast, the bacterial burden in TLR2-deficient mice did not differ from wt mice. In addition, implants harvested from IL-1β-deficient mice had more biofilm formation and 14-fold higher adherent bacteria compared with those from wt mice. Finally, IL-1β-deficient mice had ∼50% decreased neutrophil recruitment to the infected postoperative joints than wt mice. Taken together, these findings suggest a mechanism by which IL-1β induces neutrophil recruitment to help control the bacterial burden and the ensuing biofilm formation in a post-surgical joint. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc

Comparison of complication rates in reverse total shoulder arthroplasty performed for degenerative conditions versus proximal humerus fractures

Background: Indications for reverse total shoulder arthroplasty (RTSA) have been expanding. In addition to degenerative joint disease (DJD), RTSA is now being used to treat proximal humerus fractures (PHF). The purpose of this study was to compare postoperative complications in RTSA performed for DJD versus PHF. Methods: A retrospective analysis of the PearlDiver National Database was performed. International Classification of Diseases 10 codes were used to identify RTSA patients from 2015-2018 and separate them into DJD and PHF cohorts. Demographics, comorbidities, and hospital data were identified and compared using a two-sample t-test and chi-squared test. Systemic complications at 90 days and surgical complications at 90 days, 1 year, and 2 years were compared using multivariable logistic regression. Results: Fifteen thousand six hundred seventy eight patients (92.6% DJD, 7.4% PHF) were identified. PHF patients were more likely to be older (70.3 vs. 69.7 years, P = .026), female (83.5% vs. 62.2%, P < .001), and have more medical comorbidities (Charlson Comorbidity Index 3.42 vs. 3.17, P = .006) than DJD patients. After controlling for patient factors, PHF patients were more likely than DJD patients to develop urinary tract infection (odds ratio [OR] 1.65, P < .001), deep vein thrombosis (OR 1.76, P = .024), and hematoma (OR 3.83, P < .001) within 90 days of RTSA. At 90 days, 1 year, and 2 years postoperatively, RTSA for PHF patients were also more likely than RTSA for DJD patients to sustain a periprosthetic fracture (OR 2.57, P < .001) and instability (OR 2.02, P < .001). Conclusions: Patients with DJD and PHF undergoing RTSA represent different patient populations with distinct postoperative clinical outcomes. RTSA for PHF has inferior outcomes, which is significant in an era of bundled payments

Evaluation of US Orthopaedic Surgery Academic Centers Based on Measurements of Academic Achievement.

IntroductionAlthough a variety of agencies have attempted to evaluate the academic achievements of orthopaedic surgery academic centers, most use opaque criteria that are difficult to interpret and do not provide clear targets for improvement. This study leverages a weighted algorithm using objective measurements that has been linked to academic achievement to attempt to provide a comprehensive assessment of scholarly accomplishment for orthopaedic surgery academic centers.MethodsWe examined full-time faculty at 138 US orthopaedic surgery academic centers; part-time or volunteer faculty were excluded. Five metrics of academic achievement were assessed: National Institutes of Health funding (2013), number of publications, Hirschberg-index (ie, a metric of impact of publications), leadership positions held in orthopaedic surgery societies, and editorial board positions of top orthopaedic and subspecialty journals. Academic programs were given a score for every category, and the algorithm was used to calculate an overall score of academic achievement for each program.ResultsThe five most academically productive programs were Washington University in St. Louis, Hospital for Special Surgery, Mayo Clinic, University of Pennsylvania, and Thomas Jefferson University.ConclusionThis algorithm may provide faculty with an assessment tool that can establish benchmarks to help focus efforts toward increasing the academic productivity of their respective programs