Alexandra I. Stavrakis

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

Background 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. Methodology/Principal Findings 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 5×103 and 5×104 CFUs developed increased bacterial counts with marked swelling of the affected leg, consistent with an acute joint infection. In contrast, mice inoculated with 5×102 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. Conclusions/Significance 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.

Disappointing Short-Term Results With the DePuy ASR XL Metal-on-Metal Total Hip Arthroplasty

Outcomes of ultralarge-diameter femoral heads used in metal-on-metal (MOM) total hip arthroplasty (THA) are relatively unknown. This study reports on early failures of the ASR XL (Depuy, Warsaw, Ind) and assesses whether a correlation with cup positioning exists. A retrospective review of 70 consecutive MOM THAs with ultralarge-diameter femoral head and monoblock acetabular component was conducted. Minimum follow-up was 24 months. Of 70 THAs, 12 (17.1%) required revision within 3 years for pain (7), loosening (3), and squeaking (2). Three additional THAs noted squeaking, 2 noted grinding, and 3 additional hips had persistent pain. In total, 20 (28.6%) of 70 demonstrated implant dysfunction. Acetabular components for all symptomatic hips were in acceptable range of cup abduction and anteversion. The failures noted with this design do not correlate to cup placement. The high rate of implant dysfunction at early follow-up suggests serious concerns with the concept of MOM THA with an ultralarge-diameter femoral head paired with a monoblock acetabular cup.

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.

Trends in Complication Rates Following Ankle Arthrodesis and Total Ankle Replacement

BACKGROUND This study provides an updated comparison of the reoperation rates following primary ankle arthrodesis and total ankle replacement on the basis of observational, population-based data from California. We previously reported data from 1995 to 2004, and our current study includes new data from 2005 to 2010. Our hypothesis was that total ankle replacement would demonstrate increasing utilization and lower complication rates given advances in implant design and growth in surgeon experience. METHODS Californias hospital discharge database was used to identify patients who had undergone primary ankle arthrodesis or total ankle replacement between 1995 and 2010. Short-term outcomes examined were based on Centers for Medicaid & Medicare Services (CMS) surgical quality measures and included readmission for any cause, death, and readmission for 7 common surgical complications (acute myocardial infarction, pneumonia, sepsis, pulmonary embolism, mechanical complications, surgical-site bleeding, and periprosthetic joint infection or wound infection). Long-term outcomes analyzed included rates of major revision surgery (ankle arthrodesis or ankle replacement, adjacent joint procedures (subtalar arthrodesis, triple arthrodesis, tarsometatarsal arthrodesis, and total knee replacement), and below-the-knee amputation. Logistic and proportional hazard regression models were used to estimate the impact of ankle arthrodesis or total ankle replacement on the rates of adverse outcomes, with adjustment for patient factors such as age, sex, race, type of health insurance, and comorbidities. We also compared patients in the 2005 to 2010 cohort with those in the earlier cohort. RESULTS In all, 8,491 ankle arthrodesis and 1,280 total ankle replacement cases were identified. Patients managed with ankle replacement were more likely to be female, white, and older and to have Medicare or private health insurance. Short-term complication risk was low for both procedures, and patients managed with total ankle replacement had significantly lower rates of readmission (p < 0.0001) and periprosthetic joint infection/wound infection (p = 0.02) compared with patients managed with ankle arthrodesis. CONCLUSIONS The inclusion of new data on patients who underwent surgery between 2005 and 2010 demonstrates increasing utilization and lower complication rates for total ankle replacement compared with ankle arthrodesis. These findings suggest that there have been improvements in the clinical safety of total ankle replacement over time. LEVEL OF EVIDENCE Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Bilateral Total Hip Arthroplasty has Similar Complication Rates to Unilateral Total Hip Arthroplasty.

Simultaneous bilateral THA has several advantages over staged THA, however its safety has not been well examined. This study reports a statewide 15-year experience of simultaneous bilateral THA and compares its complications to those of unilateral THA. Logistic regression was used to determine the role of bilateral surgery as a predictor of complications while correcting for patient comorbidities. Of 202,986 patients, 1.1% underwent bilateral THA. Bilateral THA was more commonly performed in males, younger patients, those with private insurance, and at higher volume hospitals. There was no difference in 30-day readmissions or revision surgeries. There was a higher rate of sepsis in the bilateral group but no difference in other complications. This study demonstrates that THA is a safe option in appropriately selected patients.

A Comparison of the Incidence of Complications Following Total Hip Arthroplasty in Patients With or Without Osteonecrosis

Osteonecrosis (ON) is a common cause of hip arthritis requiring arthroplasty (THA). ON patients often have associated conditions that place them at a greater risk for complications. The aim of this study is to determine complication rates of ON versus other THA patients. Statewide hospital admissions for THA were identified (1995-2010). THA procedures and ON diagnosis were identified using ICD-9 codes. Logistic regression analysis was used to determine the role of ON as a predictor of complications. ON led to an increased risk of sepsis and readmission. There was no significant difference in mortality rate. This study demonstrates that patients with ON undergoing THA have increased rates of readmission and sepsis. These findings are helpful in allocating resources for treating this patient group.

The role of chairman and research director in influencing scholarly productivity and research funding in academic orthopaedic surgery

The purpose of this study was to determine what orthopaedic surgery department leadership characteristics are most closely correlated with securing NIH funding and increasing scholarly productivity. Scopus database was used to identify number of publications/h‐index for 4,328 faculty, department chairs (DC), and research directors (RD), listed on departmental websites from 138 academic orthopaedic departments in the United States. NIH funding data was obtained for the 2013 fiscal year. While all programs had a DC, only 46% had a RD. Of

Current Animal Models of Postoperative Spine Infection and Potential Future Advances

54,925,833 in NIH funding allocated to orthopaedic surgery faculty in 2013, 3% of faculty and 31% of departments were funded. 16% of funded institutions had a funded DC whereas 65% had a funded RD. Department productivity and funding were highly correlated to leadership productivity and funding(p< 0.05). Mean funding was

Combination Prophylactic Therapy with Rifampin Increases Efficacy against an Experimental Staphylococcus epidermidis Subcutaneous Implant-Related Infection

1,700,000 for departments with a NIH‐funded RD,

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

104,000 for departments with an unfunded RD, and