The microbial profile of infected endoprosthetic reconstructions after wide excision for patients with musculoskeletal tumors: A call for pathogen-based practices.

BACKGROUND AND OBJECTIVES: Periprosthetic infection is a devastating complication following endoprosthetic reconstruction. This study utilized a large database of endoprostheses to describe the incidence, risk factors, and microbial profile of such infections to better catalogue and understand these catastrophic events. METHODS: A retrospective review of endoprosthetic reconstructions for an oncologic indication from January 1, 1981 to December 31, 2020 was performed. Demographic, oncologic, procedural and outcome data was analyzed. Multivariable logistic regression was used to identify potential risk factors for infection with significance defined as p < 0.05. RESULTS: Forty four out of 712 (6.2%) reconstructions resulted in infection at a mean time of 39.9 ± 44.5 months. Revision surgery (odds ratio [OR] 6.14, p < 0.001) or having a postoperative wound complication (OR 7.67, p < 0.001) were significantly associated with infection. Staphylococcus aureus and Staphylococcus epidermidis were the most commonly cultured organisms at a rate of 34.1% (15/44) and 22.7% (10/44), respectively. Ten infections resulted in amputation; five due to antimicrobial-resistant infections and three due to polymicrobial infections. CONCLUSION: Understanding the microbial profile of patients undergoing endoprosthetic reconstruction is paramount. This study demonstrates a relatively high rate of polymicrobial and antibiotic-resistant infections that portend worse outcomes, thus suggesting that pathogen-specific infectious practices may be warranted. LEVEL OF EVIDENCE: Retrospective cohort study, level III.

What Is the Long-term Survivorship of Primary and Revision Cemented Distal Femoral Replacements for Limb Salvage of Patients With Sarcoma?

BACKGROUND: Cemented endoprosthetic reconstruction after resection of primary bone sarcomas has been in common use for decades. Although multiple studies have reported the survivorship of primary endoprostheses, implant survivorship after revision surgery is less well established. Given that earlier advances in systemic therapy improved survival of patients with sarcoma, the usage of revision endoprostheses can be expected to increase and, as such, understanding revision implant survivorship will help to inform patient and surgeon expectations. Additionally, as new implants are developed that allow alternative reconstruction options, a normative dataset establishing accurate expectations for revision cemented endoprostheses is a critical benchmark by which to measure progress. QUESTIONS/PURPOSES: (1) What is the implant survivorship free of all-cause revision for primary and revision cemented distal femoral replacements (DFRs) used in the treatment of malignant or benign tumors? (2) What are the most common indications for revision of primary and revision DFRs in an oncology population with mean follow-up of more than 10 years? (3) How does the indication for revision of a primary DFR affect the subsequent risk for and type of revision DFR complication? (4) What patient, tumor, or implant characteristics are associated with improved survivorship free of revision in cemented DFRs used in patients treated initially for primary malignant or benign tumors? METHODS: This was a retrospective, comparative study using our institution's longitudinally-maintained database of 806 cemented endoprostheses starting in 1980 and assessed through December 31, 2018. In all, 365 DFRs were inserted during this time, but 14% (51 of 365) were placed for nonprimary bone tumors and 1% (5 of 365) were cementless reconstructions, leaving 309 cemented DFRs. Seventy-one percent (218 of 309) were primary implants and 29 percent (91 of 309) were revision implants (used to revise a prior DFR in all patients). During this time period, our strong bias was to use cemented stems and, thus, nearly all of our patients had cemented stems. Six percent (13 of 218) of primary DFRs were implanted more than 2 years before the study end; however, they lacked 2 years of follow-up data and, thus, were considered lost to follow-up, leaving 205 implants in the primary DFR analysis group. Only the first revision after primary DFR revision surgery was included in the revision cohort analysis. Thirty-two percent (29 of 91) of revision DFRs were second or more revision patients and were excluded, leaving 62 implants in the revision analysis group. Most patients in both groups were men (57% [117 of 205] for primary and 71% [44 of 62] for revision) who had been diagnosed with osteosarcoma (75% [153 of 205] and 73% [45 of 62] for primary and revision, respectively). The primary cohort had mean age of 26 ± 16 years with a mean follow-up of 136 ± 122 months, and the revision cohort had mean age of 31 ± 13 years (p = 0.02) with 141 ± 101 months of follow-up. Study endpoints included all-cause implant revision and cause-specific revision for soft tissue complications, aseptic loosening, structural complications (defined as periprosthetic or implant fracture), infection, or tumor progression. Planned surgery for implant lengthening procedures was excluded. Implant survivorship free from all-cause revision was calculated using a competing risk (cumulative incidence) estimator with death as a competing risk. A log-rank test using chi-square analysis was used to evaluate the differences in implant survivorship between primary DFRs and first revisions. The cause-specific incidences of implant revision were tabulated for primary and revision DFRs. Cox regression analysis investigated the odds of subsequent all-cause revision surgery for revision cemented DFRs based on the primary implant complication. A binary logistic regression analysis using age, gender, indication for revision, tumor type, infection, perioperative chemotherapy, and radiation was performed to identify factors associated with a second DFR reoperation. Relative effect sizes are reported as ORs. RESULTS: The revision DFR cohort had a shorter mean survival to all-cause revision than the primary cohort (mean 10 years [95% CI 7 to 12] versus 18 years [95% CI 15 to 20]; p < 0.001). The most common complications necessitating revision for revision implants were periprosthetic or implant fracture in 37% (23 of 62) and aseptic loosening in 15% (9 of 62), and the type of primary implant complication was not associated with risk of subsequent all-cause revision surgery for revision implants. Stem diameter less than 15 mm was associated with repeat all-cause revision in cemented revision DFRs after controlling for resection length, stem length, implant fabrication (custom or modular), and presence of a porous collar (OR 4 [95% CI 1 to 17]; p = 0.03). No other parameters that we explored, including patient age, gender, chemoradiation history, or primary tumor diagnosis, were associated with repeat revision surgery. CONCLUSION: Understanding modifiable factors that can improve revision DFR survival is critical to achieving long-term limb salvage for patients with tumors around the knee. Our data suggest that utilizing implants with the largest possible stems-or at a minimum increasing the stem size over the primary implant-is important to revision cemented DFR survivorship and is an important part of our revision practice. Improving revision implants' resistance to aseptic loosening through designs that resist torsion (a common mode of cemented fixation failure)-such as with the use of custom cross-pin fabrication-may be one method to improve survivorship. Another will be improved implant metallurgy that is resistant to fatigue fracture. Next steps may include understanding the optimal ratio of femoral diaphyseal width to implant diameter in patients where anatomic constraints preclude the insertion of cemented stems 15 mm or more in diameter. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Is High-dose Radiation Therapy Associated With Early Revision Due to Aseptic Loosening in Patients With a Sarcoma of the Lower Extremities Reconstructed With a Cemented Endoprosthesis?

BACKGROUND: The durability of endoprostheses after limb salvage surgery is influenced by surgical factors (resection length, implant location, and residual bone quality), implant design (modular versus custom design, rotating versus fixed hinge, coating, collars, and the use of cross pins), and host factors (patient's immune status, activity levels, and age). In general, radiation therapy increases the risk of fractures, infection, delayed wound healing, and impaired osseointegration. Several studies have shown exposure to radiation to be associated with higher endoprosthesis revision rates and higher periprosthetic infection rates, but results are inconsistent. Although radiation therapy is not routinely used in the treatment of many bone sarcomas in current practice, it is still used in high doses after resection and prosthetic reconstruction in patients who have Ewing sarcoma with close or positive margins and in patients with soft tissue sarcoma. It is also used in varying doses after prosthetic reconstruction in patients with myeloma or bone metastasis after resection of periarticular destructive tumors. These patients may be at an increased risk of complications due to their radiation exposure, but this is a difficult question to study given the rarity of these diagnoses and poor overall survival of these patients. We therefore leveraged a large, longitudinally collected, 40-year endoprosthesis database that included patients who received radiation to the extremity for many bone and soft tissue sarcomas to investigate the association between preoperative or postoperative radiation therapy and endoprosthesis survival. QUESTIONS/PURPOSES: (1) Is receiving preoperative or postoperative radiation therapy in low or high doses for the treatment of bone or soft tissue malignancy of the lower extremities associated with decreased implant survivorship free from amputation or revision due to any cause? (2) Is receiving preoperative or postoperative radiation therapy in low or high doses for the treatment of bone or soft tissue malignancy of the lower extremities associated with decreased implant survivorship free from revision specifically due to aseptic loosening? (3) Is receiving preoperative or postoperative radiation therapy for the treatment of Ewing sarcoma of the femur specifically associated with decreased implant survivorship free from revision specifically due to aseptic loosening? METHODS: This was a retrospective, comparative study using our institution's database of 822 endoprostheses. Between 1980 and 2019, we treated 541 patients with primary cemented endoprostheses of the extremities. Of those patients, 8% (45 of 541) were excluded due to unknown radiation status, 3% (17 of 541) because of prior failed allograft, 15% (83 of 541) due to metastatic disease from a carcinoma, 1% (6 of 541) due to a nononcologic diagnosis, 4% (20 of 541) due to benign tumor diagnosis, 16% (87 of 541) due to upper extremity tumor location, 9% (49 of 541) due to not receiving chemotherapy, and 3% (14 of 541) due to expandable prostheses. Of the remaining 220 patients, 6% (13) were considered missing because they did not have 2 years of follow-up and did not reach a study endpoint. No patients had surgery within the last 2 years of the study end date. In all, 207 patients met inclusion criteria and were eligible for analysis. Patients who had received radiation to the lower extremities at any point in their treatment course were included in the radiation group and were compared with patients who did not receive radiation. For patients where radiation dose was available, the radiation group was subdivided into a low-dose (≤ 3000 cGy) and high-dose (> 3000 cGy) group. Revision surgery was defined as any surgery necessitating removal or replacement of the tibial or femoral stem. The complications necessitating revision or amputation were poor wound healing, aseptic loosening, implant breakage, deep infection, and tumor progression. The primary outcome of interest was implant survival free from revision or amputation due to any cause. The secondary outcome of interest was implant survival free from revision or amputation specifically due to aseptic loosening. The Kaplan-Meier survivorship curves were generated with implant survival free from revision or amputation as the endpoint and patient death as a competing risk. A log-rank test was used to identify differences in survivorship between the patients who received radiation and those who did not. Multivariate regression was used to identify factors associated with decreased implant survival. An odds ratio was used to determine relative effect size among the factors associated with decreased implant survival. RESULTS: The mean implant survival time for patients who did not receive radiation was 18.3 years (95% confidence interval [CI] 15.4 to 21.3) whereas the mean implant survival time for patients who received low- and high-dose radiation were 19.1 years (95% CI 14.5 to 23.7; p = 0.59) and 13.8 years (95% CI 8.2 to 19.5; p = 0.65), respectively. The mean implant survival free from revision for aseptic loosening for patients who did not receive radiation was 27.1 years (95% CI 24.1 to 30.1) whereas the mean implant survival for patients who received low- and high-dose radiation were 24.1 years (95% CI 19.1 to 29.1; p = 0.34) and 16.4 years (95% CI 10.6 to 22.2; p = 0.01), respectively. Patients who received high-dose radiation had decreased 5-year implant survivorship free from amputation or revision due to aseptic loosening (73% [95% CI 44% to 89%]) compared with patients who did not receive radiation (95% [95% CI 90% to 99%]; p = 0.01). For patients treated for Ewing sarcoma of the femur, the 5-year implant survival free from amputation or revision due to aseptic loosening for patients who did not receive radiation (100% [95% CI 100% to 100%]) was no different compared with patients who received radiation (71% [95% CI 35% to 90%]; p = 0.56). CONCLUSION: The results of this study may apply to scenarios where radiation is used, such as Ewing sarcoma with positive margins or local recurrence and after prosthetic reconstruction in patients with myeloma or bone metastasis after resection of periarticular destructive tumors. Surgeons may consider closer monitoring for early clinical and radiographic signs of aseptic loosening in patients who received high-dose radiation. These patients may also benefit from constructs that have increased resistance to aseptic loosening such as cross-pin or side plate fixation. The association between radiation and aseptic loosening should be further studied with larger studies with homogeneity in tumor diagnosis and prosthesis. The dose-dependent relationship between radiation and bone-related complications may also benefit from controlled, laboratory-based biomechanical studies. LEVEL OF EVIDENCE: Level III, therapeutic study.

Short-term outcomes of periprosthetic compared to native distal femur fractures, a national database study.

BACKGROUND: Distal femur fractures (DFFx) are highly morbid injuries with a complication rate comparable to hip fractures. Rising rates of total knee arthroplasty (TKA) have led to increasing rates of periprosthetic DFFx (pDFFx). We sought to determine how pDFFx complication rates differed from native DFFx (nDFFx). METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) was used to identify patients who sustained pDFFx or nDFFx between 2012 and 2018. Patients were further stratified by operative treatment: open reduction internal fixation (ORIF) or distal femur replacement (DFR). Multivariate logistic regression was used to compare 30-day complication rates between pDFFx versus nDFFx and, among pDFFx patients, ORIF versus DFR or revision TKA (rTKA). RESULTS: 563 patients with pDFFx and 2259 patients with nDFFx were identified between 2012 and 2018. pDFFx patients had significantly lower rates of ORIF than nDFFx patients (36.4 vs 95.4%, p < 0.001). On multivariate analysis, pDFFx were associated with a higher rate of surgical site complications (OR 2.48, p = 0.009) compared to nDFFx. There were no differences in mortality, reoperations, major complications, rate of blood transfusion, venous thromboembolism and disposition. In patients with pDFFx, patients undergoing DFR/rTKA were more likely to be discharged home versus a rehab facility, compared to those undergoing ORIF (OR 2.62, p < 0.001). CONCLUSIONS: In this first large registry study comparing pDFFx and nDFFx, we find similar outcomes between these groups in the first 30 days after surgery. Patients with pDFFx did have higher rates of surgical site complications, including infection and dehiscence. In pDFFx patients, those undergoing DFR were more likely to return home post-operatively.

Navigated and Robot-Assisted Technology in Total Knee Arthroplasty: Do Outcome Differences Achieve Minimal Clinically Important Difference?

BACKGROUND: In total knee arthroplasty (TKA), computer-assisted navigation (N-TKA) and robotic-assisted methods (RA-TKA) are intended to increase precision of mechanical and component alignment. However, the clinical significance of published patient-reported outcome measure (PROM) differences in comparison to conventional TKA (C-TKA) is unknown. METHODS: A systematic review was performed to identify all studies reporting perioperative PROMs for either primary N-TKA or RA-TKA with a C-TKA comparison cohort with a minimum 1-year follow-up. Relative improvements in PROMs for the two cohorts were compared to published minimal clinically important difference (MCID) values. RESULTS: After systematic review, 21 studies (N = 3,214) reporting on N-TKA and eight studies (N = 1,529) reporting on RA-TKA met inclusion criteria. Eighteen of 20 studies (90%) reported improved radiographic outcomes with N-TKA relative to C-TKA; five of five studies reported improved radiographic outcomes with RA-TKA relative to C-TKA. Five of 21 studies (24%) reported statistically significant greater improvements in clinical PROMs for N-TKA relative to C-TKA, whereas only two (10%) achieved clinical significance relative to MCID on a secondary analysis. One of 8 studies (13%) reported statistically significant greater improvements in PROMs for RA-TKA relative to C-TKA, whereas none achieved clinical significance relative to MCID on a secondary analysis. No studies reported a significant difference in revision rates. CONCLUSION: While most studies comparing RA-TKA and N-TKA with C-TKA demonstrate improved radiographic alignment outcomes, a minority of studies reported PROM differences that achieve clinical significance. Future studies should report data and be interpreted in the context of clinical significance to establish patient and surgeon expectations for emerging technologies.

Analysis of perioperative outcomes in hip resection arthroplasty.

BACKGROUND: Hip resection arthroplasty (HRA) is a salvage surgical technique for the management of complex hip conditions wherein arthroplasty may be contraindicated. The purpose of this study was to review modern-day indications for HRA and compare outcomes between patients undergoing HRA and revision total hip arthroplasty (RTHA). METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) was used to identify patients undergoing HRA or RTHA between 2012 and 2017. Patient demographics, risk factors, and perioperative complications were analyzed. Multivariate regression was used to determine predictors of early postoperative complications. Propensity score matching (PSM) was performed to compare relative risks (RR) of complications in HRA compared to RTHA. RESULTS: 290 patients underwent HRA between 2012 and 2017. Infection was the most common indication for HRA (39.8%), followed by femoral neck fracture or malunion/nonunion (26%) and prosthetic instability (12.2%). Increased body mass index (BMI) (p = 0.012) and chronic obstructive pulmonary disease (COPD) (p = 0.007) were associated with increased risk of complication in HRA. There were no significant differences in short-term complication risks between RTHA and HRA. CONCLUSIONS: HRA was associated with short-term complication rates comparable to RTHA. These findings may help in surgical decision-making and appropriate indications in the present day. LEVEL OF EVIDENCE: III.

Metaphyseal Stem Tip Location is a Risk Factor for Aseptic Loosening of Cemented Distal Femoral Replacements.

BACKGROUND: The objective of this study was to describe the incidence of aseptic loosening (AL) of cemented stem distal femoral replacements (DFR) and to identify modifiable risk factors for its development. METHODS: A retrospective review was performed of 245 consecutive primary, cemented stem DFRs implanted at a single institution over a 40-year period. The primary outcome was revision surgery for AL. A multivariate analysis was performed to identify risk factors for AL. Radiographs were reviewed to identify stem tip location, which was defined as diaphyseal or metaphyseal. Implant survival to AL was compared using Kaplan-Meier analysis. RESULTS: AL and structural failure were the most common causes of implant failure (incidence 11.8%, 29/245). Younger age (P = .002), male sex (P = .01), longer resection length (P = .04), and nonmodular implants (P = .002) were all significantly associated with AL. After 1:1 matching, stem tip location in metaphyseal bone was independently associated with AL (P = .04). 36% (9/25) of implants that loosened had a stem tip located in the metaphysis vs only 8% (2/25) of implants that did not fail. 30-year survival to AL was lower for implants with a metaphyseal stem tip than implants with a diaphyseal stem tip (22.7% vs 47.6%; P = .11). CONCLUSION: A stem tip location in metaphyseal bone is associated with diminished survival to AL. When templating before DFR, stem tip location can assist in identifying high-risk reconstructions that may benefit from alternative or supplemental fixation techniques to prevent the development of AL.

Reverse Obliquity Intertrochanteric Femur Fractures: Technical Tips to Avoid Failure.

SUMMARY: Reverse obliquity intertrochanteric femur fractures represent a substantial proportion of all trochanteric hip fractures. These challenging fracture patterns are unique, with their primary fracture plane from distal-lateral to proximal-medial. The use of modern cephalomedullary fixation has yielded successful results, although technical factors including avoiding malreduction and preventing collapse remain challenging. The use of adjunctive techniques including cerclage wires, colinear clamps, and mini-fragment plates can facilitate reduction efforts. The purpose of this article was to review technical tips and common pitfalls in the operative treatment of reverse obliquity intertrochanteric femur fractures.

Epidemiology of Revision Total Knee Arthroplasty in the United States, 2012 to 2019.

Background: As primary total knee arthroplasty volume continues to increase, so will the number of revision total knee arthroplasty (rTKA) procedures. The purpose of this study is to provide an updated perspective on the incidence, indications, and financial burden of rTKA in the United States. Material and methods: This was a retrospective epidemiologic analysis using the National Inpatient Sample. International Classification of Diseases ninth and tenth revision codes were used to identify patients who underwent rTKA and create cohorts based on rTKA indications from 2012 to 2019. National and regional trends for length of stay, cost, and discharge location were evaluated. Results: A total of 505,160 rTKA procedures were identified. The annual number of rTKA procedures increased by 29.6% over the study period (56,490 to 73,205). The top 3 indications for rTKA were aseptic loosening (23.1%), periprosthetic joint infection (PJI) (20.4%), and instability (11.0%). Over the study period, the proportion of patients discharged to skilled nursing facility decreased from 31.7% to 24.1% (P < .001). Hospital length of stay decreased from 4.0 days in 2012 to 3.8 days in 2019 (P < .001). Hospital costs increased by $1300 from $25,730 to $27,077 (P < .001). The proportion of rTKA cases performed at urban academic centers increased (52.1% to 74.3%, P < .001) while that at urban nonacademic centers decreased (39.0% to 19.2%, P < .001). Conclusion: The top 3 indications for rTKA were aseptic loosening, PJI, and instability, with PJI becoming the most common indication in 2019. These cases are increasingly being performed at urban academic centers and away from urban nonacademic centers. Level of Evidence: 3 (Retrospective cohort study).

Analysis of Medical Malpractice Outcomes for Sports Orthopedic Procedures.

Orthopedic sports medicine surgeons are especially vulnerable to litigation, largely because of high patient expectations in the setting of complex surgeries. Understanding the factors associated with litigation may reduce physician risk as well as optimize patient satisfaction and outcomes. We used a national medicolegal database to search for medical malpractice verdicts and out-of-court settlements involving common sports injuries and their surgical management between January 1, 2000, and January 1, 2018. Univariate analysis was performed to identify predictors of case outcome and monetary awards. We identified 777 cases, but only 328 met the inclusion criteria. Of the 328 cases included in our study, 231 (70.4%) resulted in a defendant verdict, 75 (22.9%) resulted in a plaintiff verdict, and 22 (6.7%) resulted in a settlement. The most common reason for litigation was intraoperative error (183 cases, 55.8%). No statistically significant difference was found between monetary awards for plaintiff verdicts vs settlements (mean award of $1.29 million and $0.72 million, respectively, P=.07). Cases in which the plaintiff claimed neurovascular injury were significantly more likely to result in a higher monetary award (mean award of $2.37 million, P=.02). Cases involving an incorrect surgical site were significantly less likely to result in a defendant outcome, with 7 of 12 cases (58.3%) leading to a plaintiff outcome (P=.047). With more than two-thirds of cases resulting in a defendant verdict, many suits result in a favorable outcome for practitioners. Intraoperative error is the most common reason for litigation, and neurovascular injury resulted in the highest monetary payouts. Vigilance to avoid these events may improve patient outcomes and decrease liability to practitioners. [Orthopedics. 2022;45(1):e47-e52.].

Analysis of the Digital Footprint of Orthopaedic Surgeons.

INTRODUCTION: Patients increasingly rely on Google search to guide their choice of healthcare providers. Despite this trend, there is limited literature systematically characterizing the online presence of orthopaedic surgeons. The goal of this study was to identify the information patients see after queries of Google search when selecting orthopaedic surgeon providers. METHODS: The Physician Comparable downloadable file from the Centers for Medicare and Medicaid Services was deduplicated and filtered. A list of orthopaedic surgeons within the United States was generated, of which a randomized sample was taken and queried using a Google Custom Search. The results for each surgeon's first page were classified into the following categories: (1) hospital-controlled content website, (2) third-party health website, (3) social media website, (4) primary academic journals, or (5) other. RESULTS: The most frequently returned website was third-party health websites (43.3%). Statistically significant differences were observed in the categories across multiple comparisons, including academic and nonacademic orthopaedic surgeons, male and female providers, and surgeons from different graduation years. DISCUSSION: Most of the results were attributed to third-party websites demonstrating that orthopaedic surgeons do not have notable control over their digital footprint. Increased patient visibility of physician-controlled websites and an objective rating system for patients remain potential areas of growth.

Instability Is the Most Common Indication for Revision Hip Arthroplasty in the United States: National Trends From 2012 to 2018.

BACKGROUND: As primary total hip arthroplasty volume continues to increase, so will the number of revision total hip arthroplasty (rTHA) procedures. These complex cases represent a significant clinical and financial burden to the health-care system. METHODS: This was a retrospective review using the National Inpatient Sample. International Classification of Diseases, 9th and 10th revision codes were used to identify patients who underwent rTHA and create cohorts based on rTHA indications from 2012 to 2018. National and regional trends for length of stay (LOS), cost, and discharge location were evaluated. RESULTS: A total of 292,250 rTHA procedures were identified. The annual number of rTHA procedures increased by 28.1% from 2012 to 2018 (37,325 to 47,810). The top 3 indications for rTHA were instability (20.4%), aseptic loosening (17.8%), and infection (11.1%). Over the study period, the proportion of patients discharged to skilled nursing facility decreased from 44.2% to 38% (P < .001). Hospital LOS decreased on average from 4.8 to 4.4 days (P < .001). Infections had the highest average LOS (7.3 days) followed by periprosthetic fractures (6.5 days). Hospital costs decreased over the study period, from $25,794 to $24,555 (P < .001). The proportion of rTHA cases performed at urban academic centers increased (58.0% to 75.3%, P < .001) while the proportion performed at urban nonacademic centers decreased (35.5% to 19.4%, P < .001). CONCLUSION: Instability was the most common indication for rTHA between 2012 and 2018. The proportion of rTHA performed in urban academic centers has increased substantially, away from urban nonacademic centers. While cost and LOS have decreased, significant geographic variability exists.

Trends in Operative Time and Short-Term Outcomes After Conventional and Navigated Total Knee Arthroplasty.

BACKGROUND: Adoption of navigated total knee arthroplasty (Nav-TKA) is increasing. However, it has been suggested that a perceived decrease in surgical efficiency and a lack of proven superior functional outcomes associated with Nav-TKA have hindered its widespread adoption. METHODS: The American College of Surgeons National Surgical Quality Improvement Program was queried to identify patients who had undergone TKA with or without navigation between 2012 and 2018. Patients were further subclassified based on the type of navigation used, image-guided or imageless. Multivariate logistic regression was used to compare operative time and 30-day complication rates between conventional TKA (Conv-TKA) and Nav-TKA with and without image guidance. RESULTS: A total of 316,210 Conv-TKAs and 8554 Nav-TKAs (8270 imageless, 284 image-guided) were identified. Across the study period, the use of Nav-TKA was associated with a 1.5-minute increase in operative time. However, the overall time burden decreased over the study period, and by 2018, the mean operative time for Nav-TKA was 2.4 minutes less than that of Conv-TKA. Compared with Conv-TKA, Nav-TKA was associated with decreased rates of postoperative transfusion and surgical site complications but a similar incidence of systemic thromboembolism. CONCLUSIONS: This is the first large-scale database study to examine the differences in operative time between Conv-TKA and Nav-TKA. The time burden associated with Nav-TKA decreased over the study period and even reversed by 2018. Nav-TKA was associated with lower rates of postoperative transfusion and surgical site complications. Further studies are needed to evaluate the long-term and functional outcomes between conventional and navigated knee arthroplasty techniques.

Platelet Deficiency Represents a Modifiable Risk Factor for Periprosthetic Joint Infection in a Preclinical Mouse Model.

BACKGROUND: Well known for their hemostatic function, platelets are increasingly becoming recognized as important immunomodulators. The purpose of the present study was to assess the impact of platelet depletion on antimicrobial host defense in a mouse model of periprosthetic joint infection (PJI). METHODS: Thrombocytopenia (TCP) was induced in C57BL/6 mice with use of a selective antibody against platelet CD41 (anti-CD41). Whole blood from pre-treated mice was incubated with Staphylococcus aureus to assess antimicrobial efficacy with use of bioluminescent imaging, quantitative histological staining, and colony forming unit (CFU) quantification. In parallel, untreated heterologous platelets were added to TCP blood to assess potential rescue of antimicrobial efficacy. In vivo, TCP and control mice underwent placement of a titanium implant in the femur inoculated with bioluminescent Xen36 S. aureus. Longitudinal bioluminescent imaging was performed postoperatively to quantify the evolution of bacterial burden, which was confirmed via assessment of S. aureus CFUs on the implant and in peri-implant tissue on postoperative day (POD) 28. RESULTS: Anti-CD41 treatment resulted in significant dose-dependent reductions in platelet count. Ex vivo, platelet-depleted whole blood demonstrated significantly less bacterial reduction than control blood. These outcomes were reversed with the addition of untreated rescue platelets. In vivo, infection burden was significantly higher in TCP mice and was inversely correlated with preoperative platelet count (r2 = 0.63, p = 0.037). Likewise, CFU quantification on POD28 was associated with increased bacterial proliferation and severity of periprosthetic infection in TCP mice compared with controls. CONCLUSIONS: Thrombocytopenia resulted in an increased bacterial burden both ex vivo and in vivo in a mouse model of PJI. CLINICAL RELEVANCE: In orthopaedic patients, deficiencies in platelet quantity or function represent an easily modifiable risk factor for PJI.

Active rheumatoid arthritis in a mouse model is not an independent risk factor for periprosthetic joint infection.

INTRODUCTION: Periprosthetic joint infection (PJI) represents a devastating complication of total joint arthroplasty associated with significant morbidity and mortality. Literature suggests a possible higher incidence of periprosthetic joint infection (PJI) in patients with rheumatoid arthritis (RA). There is, however, no consensus on this purported risk nor a well-defined mechanism. This study investigates how collagen-induced arthritis (CIA), a validated animal model of RA, impacts infectious burden in a well-established model of PJI. METHODS: Control mice were compared against CIA mice. Whole blood samples were collected to quantify systemic IgG levels via ELISA. Ex vivo respiratory burst function was measured via dihydrorhodamine assay. Ex vivo Staphylococcus aureus Xen36 burden was measured directly via colony forming unit (CFU) counts and crystal violet assay to assess biofilm formation. In vivo, surgical placement of a titanium implant through the knee joint and inoculation with S. aureus Xen36 was performed. Bacterial burden was then quantified by longitudinal bioluminescent imaging. RESULTS: Mice with CIA demonstrated significantly higher levels of systemic IgG compared with control mice (p = 0.003). Ex vivo, there was no significant difference in respiratory burst function (p = 0.89) or S. aureus bacterial burden as measured by CFU counts (p = 0.91) and crystal violet assay (p = 0.96). In vivo, no significant difference in bacterial bioluminescence between groups was found at all postoperative time points. CFU counts of both the implant and the peri-implant tissue were not significantly different between groups (p = 0.82 and 0.80, respectively). CONCLUSION: This study demonstrated no significant difference in S. aureus infectious burden between mice with CIA and control mice. These results suggest that untreated, active RA may not represent a significant intrinsic risk factor for PJI, however further mechanistic translational and clinical studies are warranted.

Inhibition of Angiotensin Converting Enzyme Impairs Anti-staphylococcal Immune Function in a Preclinical Model of Implant Infection.

Background: Evidence suggests the renin-angiotensin system (RAS) plays key immunomodulatory roles. In particular, angiotensin-converting enzyme (ACE) has been shown to play a role in antimicrobial host defense. ACE inhibitors (ACEi) and angiotensin receptor blockers (ARB) are some of the most commonly prescribed medications, especially in patients undergoing invasive surgery. Thus, the current study assessed the immunomodulatory effect of RAS-modulation in a preclinical model of implant infection. Methods:In vitro antimicrobial effects of ACEi and ARBs were first assessed. C57BL/6J mice subsequently received either an ACEi (lisinopril; 16 mg/kg/day), an ARB (losartan; 30 mg/kg/day), or no treatment. Conditioned mice blood was then utilized to quantify respiratory burst function as well as Staphylococcus aureus Xen36 burden ex vivo in each treatment group. S. aureus infectious burden for each treatment group was then assessed in vivo using a validated mouse model of implant infection. Real-time quantitation of infectious burden via bioluminescent imaging over the course of 28 days post-procedure was assessed. Host response via monocyte and neutrophil infiltration within paraspinal and spleen tissue was quantified by immunohistochemistry for F4/80 and myeloperoxidase, respectively. Results: Blood from mice treated with an ACEi demonstrated a decreased ability to eradicate bacteria when mixed with Xen36 as significantly higher levels of colony forming units (CFU) and biofilm formation was appreciated ex vivo (p < 0.05). Mice treated with an ACEi showed a higher infection burden in vivo at all times (p < 0.05) and significantly higher CFUs of bacteria on both implant and paraspinal tissue at the time of sacrifice (p < 0.05 for each comparison). There was also significantly decreased infiltration and respiratory burst function of immune effector cells in the ACEi group (p < 0.05). Conclusion: ACEi, but not ARB, treatment resulted in increased S. aureus burden and impaired immune response in a preclinical model of implant infection. These results suggest that perioperative ACEi use may represent a previously unappreciated risk factor for surgical site infection. Given the relative interchangeability of ACEi and ARB from a cardiovascular standpoint, this risk factor may be modifiable.

In vivo Mouse Model of Spinal Implant Infection.

Spine implant infections portend poor outcomes as diagnosis is challenging and surgical eradication is at odds with mechanical spinal stability. The purpose of this method is to describe a novel mouse model of spinal implant infection (SII) that was created to provide an inexpensive, rapid, and accurate in vivo tool to test potential therapeutics and treatment strategies for spinal implant infections. In this method, we present a model of posterior-approach spinal surgery in which a stainless-steel k-wire is transfixed into the L4 spinous process of 12-week old C57BL/6J wild-type mice and inoculated with 1 x 103 CFU of a bioluminescent strain of Staphylococcus aureus Xen36 bacteria. Mice are then longitudinally imaged for bioluminescence in vivo on post-operative days 0, 1, 3, 5, 7, 10, 14, 18, 21, 25, 28, and 35. Bioluminescence imaging (BLI) signals from a standardized field of view are quantified to measure in vivo bacterial burden. To quantify bacteria adhering to implants and peri-implant tissue, mice are euthanized and the implant and surrounding soft tissue are harvested. Bacteria are detached from the implant by sonication, cultured overnight and then colony forming units (CFUs) are counted. The results acquired from this method include longitudinal bacterial counts as measured by in vivo S. aureus bioluminescence (mean maximum flux) and CFU counts following euthanasia. While prior animal models of instrumented spine infection have involved invasive, ex vivo tissue analysis, the mouse model of SII presented in this paper leverages noninvasive, real time in vivo optical imaging of bioluminescent bacteria to replace static tissue study. Applications of the model are broad and may include utilizing alternative bioluminescent bacterial strains, incorporating other types of genetically engineered mice to contemporaneously study host immune response, and evaluating current or investigating new diagnostic and therapeutic modalities such as antibiotics or implant coatings.

The progesterone antagonist mifepristone/RU486 blocks the negative effect on life span caused by mating in female Drosophila.

Mating causes decreased life span in female Drosophila. Here we report that mifepristone blocked this effect, yielding life span increases up to +68%. Drug was fed to females after mating, in the absence of males, demonstrating function in females. Mifepristone did not increase life span of virgin females or males. Mifepristone reduced progeny production but did not reduce food intake. High-throughput RNA sequencing was used to identify genes up-regulated or down-regulated upon mating, and where the change was reduced by mifepristone. Five candidate positive regulators of life span were identified, including dosage compensation regulator Unr and three X-linked genes: multi sex combs (PcG gene), Dopamine 2-like receptor and CG14215. The 37 candidate negative genes included neuropeptide CNMamide and several involved in protein mobilization and immune response. The results inform the interpretation of experiments involving mifepristone, and implicate steroid hormone signaling in regulating the trade-off between reproduction and life span.