Aims

Aseptic loosening is a leading cause of uncemented arthroplasty failure, often accompanied by fibrotic tissue at the bone-implant interface. A biological target, neutrophil extracellular traps (NETs), was investigated as a crucial connection between the innate immune system’s response to injury, fibrotic tissue development, and proper bone healing. Prevalence of NETs in peri-implant fibrotic tissue from aseptic loosening patients was assessed. A murine model of osseointegration failure was used to test the hypothesis that inhibition (through Pad4^-/- mice that display defects in peptidyl arginine deiminase 4 (PAD4), an essential protein required for NETs) or resolution (via DNase 1 treatment, an enzyme that degrades the cytotoxic DNA matrix) of NETs can prevent osseointegration failure and formation of peri-implant fibrotic tissue.

Introduction. Patients with aseptic loosening, a cause of failure in uncemented total joint arthroplasty (TJA), often present with fibrous tissue at the bone-implant interface. 1. In this study, we characterize the presence of neutrophil extracellular traps (NETs) in the intramedullary fibrotic membrane of aseptic loosening patients. We further explore the role of NETs, mediated by peptidyl arginine deiminase (PAD4), in peri-implant fibrosis and osseointegration failure through a murine model of unstable tibial implantation. 2–4. Methods. Peri-implant membrane was retrieved from five patients during total hip revision surgery and analyzed for the presence of NETs (citH3+ with extracellular DNA) via immunofluorescence. A Ti-6Al-4V implant was inserted in an oversized drill-hole in the right proximal tibia of 8-week-old C57BL/6J and PAD4 knockout mice (n=3 per group). Fourteen days later, all mice were euthanized, and implanted tibias were dissected. Fibrosis and osseointegration at the bone-implant interface were assessed by micro-computed tomography (microCT) and hematoxylin and eosin (H&E) staining. H&E samples were scored blindly by the investigator and another observer for signs of poor (score=0) to excellent osseointegration (score=3) using a rubric established in our lab. Results. NETs were found in peri-implant membrane collected from aseptic loosening patients (Figure 1a) and at the bone-implant interface in a murine model (Figure 1b). Unstable implants in wild type mice failed to osseointegrate, indicated by presence of fibroblast-like cells (dashed arrow), immature bone matrix (Figure 1c), low bone volume fraction (BV/TV) and bone surface area (BS) (Figure 1e). Unstable implants in PAD4. −/−. mice showed signs of good osseointegration such as mature trabeculae (solid arrow) (Figure 1d), higher BV/TV (p<0.10) and BS (p<0.05) (Figure 1f). Histological osseointegration scoring indicated wildtype mice exhibited an average score of 0.83 and PAD4. −/−. exhibited an average score of 2.5 (p<0.05, weighted Cohen's kappa = 0.714) (Figure 1g). Conclusion. NETs were characterized in fibrotic tissue in both aseptic loosening patients and in a murine model of unstable tibial implantation. NET inhibition was able to successfully prevent peri-implant fibrosis and osseointegration failure, leading the way for a potential novel non-invasive therapeutic approach for the treatment of aseptic loosening. For any figures, tables, or references, please contact the authors directly

Introduction. PJI is a devastating complication following total joint arthroplasty. In this study, we explore the efficacy of a bacteriophage-derived lysin, PlySs2, against in-vitro biofilm on titanium implant surfaces and in an acute in-vivo murine debridement antibiotic implant retention (DAIR) model of PJI. Methods. In-vitro: Xen 36 S. aureus biofilm was grown on Ti-6Al-4V mouse tibial implants for 1 day or 5 days and subsequently exposed to growth media, 1000× minimal inhibitory concentration (MIC) Vancomycin, or 5× MIC PlySs2. Implants were sonicated and analyzed for Colony Forming Units (CFU). In-vivo: A Ti-6Al-4V implant was inserted into the proximal tibia of C57BL/6J mice (n=21). All mice received 10. 4. CFU inoculation of Xen 36 S. aureus to the knee joint capsule and the infection was permitted 5 days to progress. On day 5 the mice were separated into three groups (n=7/group): (1) no further surgical intervention (control group), (2) irrigation and debridement (I&D) with saline, (3) I&D with 2mg/mL PlySs2. No implant-exchange was performed to mimic a debridement, antibiotic, and implant retention (DAIR) therapeutic strategy. All mice were sacrificed at day 10. Results. CFU counts for 1-day and 5-day in-vitro grown biofilm on implants demonstrate a >3log-fold reduction with PlySs2 compared to Vancomycin (p=0.01) with no significant difference between Vancomycin and control. In-vivo the addition of PlySs2 to Vancomycin treated mice reduces bacterial load in the periposthetic tissue and implant (p<0.05) with 5 days of treatment. Conclusion. PlySs2 5× MIC exhibits superior anti-microbial effect compared to Vancomycin on implants with 1-day and 5–5day biofilm maturities. The addition of PlySs2 to Vancomycin treatment of an acute established PJI further reduces tissue CFU and implants CFU. For any tables or figures, please contact the authors directly

The unparalleled events of the year 2020 continue to evolve and challenge the worldwide community on a daily basis. The COVID-19 pandemic has had a major impact on all aspects of our lives, and has caused major morbidity and mortality around the globe. The impact of COVID-19 on the practice of orthopedic surgery has been substantial with practice shutdowns, elective surgery restrictions, heightened utilization of telemedicine platforms and implementation of precautionary measures for in-person clinic visits. During this transition period the scholarly and educational pursuits of academic surgeons have been de-emphasized as the more immediate demands of clinical practice survivorship have been the priority. This unavoidable focus on clinical practice has heightened the importance of orthopedic subspecialty societies in maintaining an appropriate level of attention on research and educational activities. Under the outstanding presidential leadership of Robert Barrack, MD, The Hip Society adapted to the profound challenges of 2020, and maintained strong leadership in the realms of education and research. The recent 2020 summer meeting of the Hip Society was a testimonial to the resilience and dedication of the Society members to ongoing innovation in research and education. Due to travel and social distancing restrictions the 2020 summer meeting was transitioned from an in-person to a virtual meeting format. Dr Barrack and Program Chair Dr John Clohisy assisted with oversight of the meeting, while Olga Foley and Cynthia Garcia ensured the success of the meeting with remarkable planning and organization. These collaborative efforts resulted in an organized, well-attended, high level scientific meeting with engaging discussion and a remarkable virtual conference environment. The Bone & Joint Journal is very pleased to partner with The Hip Society to publish the proceedings of this very unique virtual meeting. The Hip Society is based in the United States and membership is granted to select individuals for leadership accomplishments in education and research related to hip disease. The Society is focused on the mission of advancing the knowledge and treatment of hip disorders to improve the lives of patients. The vision of the Hip Society is to lead in the discovery and dissemination of knowledge related to disorders of the hip. The annual closed meeting is one of the most important events of the society as this gathering highlights timely, controversial and novel research contributions from the membership. The top research papers from The Hip Society meeting will be published and made available to the wider orthopedic community in The Bone & Joint Journal. This partnership with The Bone & Joint Journal enhances the mission and vision of The Hip Society by international dissemination of the meeting proceedings. Given the far-reaching circulation of The Bone & Joint Journal the highest quality work is available to an expanding body of surgeons, associated healthcare providers and patients. Ultimately, this facilitates the overarching Hip Society goal of improving the lives of our patients. The 2020 virtual Hip Society meeting was characterized by outstanding member attendance, high quality paper presentations and robust discussion sessions. The meeting was held over two days and encompassed 58 open paper presentations divided into ten sessions with moderated discussions after each session. All papers will be presented in this issue in abstract form, while selected full papers passing our rigorous peer review process will be available online and in The Bone & Joint Journal in a dedicated supplement in 2021. The first session of the meeting focused on issues related to complex primary THA and osteonecrosis of the femoral head. Dr Gross presented on the conversion of hip fusion to THA in 28 patents at a mean 7 years. He reported a high clinical success rate, yet complications of heterotopic ossification and neurologic injury were relatively common. Consideration of heterotopic ossification prophylaxis and the selective use of a constrained liner were recommended. Dr Pagnano summarized the use of various contemporary porous acetabular components in 38 hips in the setting of prior pelvic radiation. The mean follow-up was 5 years and 10 year survivorship was 100% with all implants radiographically fixed. Dr Bolognesi's study demonstrated that THA in solid organ transplant patients is associated with higher risk for facility placement, transfusions and readmissions. This patient population also has increased mortality risk (4.3% risk at 1 year) especially lung transplant patients. The second group of papers focused on femoral head osteonecrosis. Dr Iorio presented single center data demonstrating that CT scan was a useful adjunct for diagnosis in the staging work-up for cancer, yet was not useful for ARCO staging and treatment decision-making. On the basic science side, Dr Goodman utilized a rabbit model of steroid-induced femoral head osteonecrosis to determine that immunomodulation with IL-4 has the potential to improve bone healing after core decompression. The session was concluded by Dr Nelson's study of ceramic-on-ceramic THA in 108 osteonecrosis patients. The median 12 year results were outstanding with marked increases in PROs, maintenance of high activity levels, and a 3.7% revision rate. In the second session attention was directed to THA instability and spinopelvic mobility. Dr Sierra presented a machine learning algorithm for THA dislocation risk. Two modifiable variables (anterior/lateral approach, elevated liner) were most influential in minimizing dislocation risk. Dr Taunton's study demonstrated a deep learning artificial intelligence model derived from postoperative radiographs to predict THA dislocation risk. High sensitivity and negative predictive value suggest that this model may be helpful in assessing postoperative dislocation risk. In reviewing a large single-center, multiple surgeon cohort of 2,831 DAA procedures, Dr Moskal noted a very low dislocation rate (0.45%) at minimum 2 years. Importantly, spinopelvic pathology or prior spinal instrumentation was not associated with an increased dislocation risk (0.30%). Dr Huo and colleagues analyzed pelvic tilt during functional gait in patients with acetabular dysplasia. They detected variable pelvic tilt on different surfaces with the data suggesting that patients with more anterior pelvic tilt while standing tend to have greater compensatory posterior pelvic tilt during gait. Dr Lamontagne reported on the sagittal and axial spinomobility in patients with hip OA, and highlighted reductions in pelvic tilt, pelvic-femoral-angle, lumbar lordosis and seated maximal trunk rotation when compared to controls. Dr Dennis showed that differences in spinopelvic mobility may explain the variable accuracy of acetabular version measurements on the cross-table lateral radiographs. Dr Gwo-Chin presented on a comprehensive functional analysis of 1,592 patients undergoing THA and observed that spinopelvic abnormalities are not infrequent (14%) in THA patients. Consistent with these findings Dr Murphy and collaborators identified a low prevalence of previous spinal instrumentation (1.5%), yet a high prevalence of spine stiffness (27.6%) in 149 patients undergoing THA. Session three highlighted various aspects of treating hip disease in young patients. Dr Peters investigated the need for subsequent hip arthroscopy in 272 patients treated with an isolated PAO. Only 4.8% of these patients required subsequent arthroscopy calling into question the routine use of combined arthroscopy and PAO. Three papers addressed questions related to THA in young patients. Dr Berend's study of 2532 hips demonstrated that high activity level was not associated with an increased risk of midterm aseptic or all cause failure. Dr Nunley presented on 43 young patients with an average age of 52 years treated with a cementless stem and modular dual mobility articulation. Stress shielding was minimal and no concerning metal ion release detected. Dr Garvin summarized minimum 15 year data of THA with highly cross-linked polyethylene in patient less than 50 years. These hips performed exceptionally well with no mechanical loosening or radiographic osteolysis. Dr Engh examined 10 year results of the Birmingham Hip Resurfacing implant and reported a 92.9 % overall survivorship, with males less than 55 years achieving a 98.3% survivorship. The session was concluded by long-term data on the Conserve Plus hip resurfacing arthroplasty. Dr Amstutz presented an impressive dataset depicting an 83.1% 20 year survivorship for this early resurfacing cohort. Direct anterior approach total hip arthroplasty was the focus of session four. Dr Meneghini reported on the anesthesia and surgical times of direct anterior and posterior approaches from a large healthcare system database. These data suggested longer OR and surgical times for the DAA both in the inpatient and ASC environments. Dr Clohisy introduced the technique and early outcomes of lateral decubitus position DAA. In a learning curve experience of 257 hips. 96% of acetabular components were in the Lewinneck safe zone, the aseptic revision rate was 0.9% and there were no dislocations. Dr Beaule analyzed femoral stem cement mantle with the DAA and posterior approaches by comparing two matched cohorts. Stem alignment and cement mantle quality were equivalent with both approaches. Similarly, Dr Emerson demonstrated technical feasibility and fewer cemented femoral stem failures when compared to cementless stems in a series of 360 DAAs THAs. The final paper of the session presented by Dr Hamilton examined the impact of surgical approach on dislocation after isolated head and liner exchange. Neither the posterior nor the anterior approach was superior in reducing the dislocation rate for these high dislocation risk procedures. The fifth session explored contemporary topics related to anesthesia and pain management. Dr Byrd opened the session with a comparative study evaluating general versus spinal anesthesia for hip arthroscopy. This preliminary study was provoked by the desire to minimize aerosolized exposure early in the COVID-19 pandemic by transitioning to spinal anesthesia. Both anesthetic methods were effective. Dr Austin presented a randomized, double-blind controlled trial comparing spinal anesthetic with mepivacaine, hyperbaric bupivacaine and isobaric bupivacaine. Mepivacaine patients ambulated earlier and were more likely to be discharged the same day. Dr Mont provided a very timely study on the effects of “cannabis use disorder” and THA outcomes. This administrative database study of 44,154 patients revealed this disorder to be associated with longer hospital stays, increased complications rates and higher costs. Dr Bedair investigated whether a highly porous acetabular component submerged in an analgesic solution could enhance perioperative pain management. Interestingly, this novel strategy was associated with a reduction of postoperative pain scores and opioid consumption in 100 experimental patients compared to 100 controls. The concluding paper of the session by Dr Della Valle examined whether decreased discharge opioids led to increased postoperative opioid refills. A large single-center study of 19,428 patients detected a slight increase (5%) in opioid refills but a reduction in total refill morphine milligram equivalents. The final, sixth session of day one considered various challenging aspects of revision hip arthroplasty. Dr Nam started the session with review of preliminary results from a randomized control trial comparing closed incision negative-pressure therapy with a silver-impregnated dressing for wound management in 113 hips undergoing revision arthroplasty. Unlike previous reports, the negative pressure therapy was associated with a higher reoperation rate for wound-related complications. Dr Bostrom highlighted the potential clinical impact of basic biological interventions by establishing the presence of Neutrophil Extracellular Traps (NETS) in fibrotic tissue from human aseptic loosening specimens and in a murine model of unstable tibial implantation. NET inhibition in the murine model prevented the expected tibial implant osseointegration failure. Dr Lombardi presented early 3.3 year clinical results of a highly porous Ti6al4v acetabular component in complex primary and revision arthroplasty. Survivorship for aseptic loosening was 96.6 % and 95.3% for the primary and revision cases, respectively. Dr Schwarzkopf and colleagues explored the impact of time to revision arthroplasty on clinical outcomes. Analysis of 188 revision cases revealed early revisions (less than 2 years from primary) were associated with worse outcomes, longer hospitalizations and higher reoperation rates. Mid-term results for modular dual mobility implants in revision arthroplasty were reviewed by Dr Lachiewicz who reported on 126 hips at a mean 5.5 years. 11% of hips dislocated and the 6 year survival was 91%. An outer head diameter of 48mm or greater was associated with a lower risk of dislocation. Dr Berry concluded the session by discussing the outcomes of treating the challenging problem of interprosthetic femur fractures. A single-center study of 77 cases treated over 32 years demonstrated a 79% success rate free of reoperation at 2 years with 95% of patients being ambulatory. The second day commenced with the seventh session evaluating recent strategies to improve short-term THA outcomes. Dr Bozic and colleagues investigated the association of quality measure public reporting with hip/knee replacement outcomes. Annual trend data from 2010–2011 and 2016–2017 indicate that hospital-level complication and readmission rates decease after the start of public reporting, yet it is difficult to prove a direct effect. Dr Slover reviewed his institutions experience with the Comprehensive Care for Joint Replacement (CJR) model and emphasized that lower CJR target prices make it increasingly difficult for programs to meet target price thresholds. Cost saving strategies including same day discharge and reduction of home health services may result in smaller losses of positive margins. Dr Barsoum reported on the influence of patient and procedure-related risk factors of length of stay after THA. Patient-related risk factors provided substantial predictive value yet procedure-related risk factors (hospital site and surgical approach) remain the main drivers of predicting length of stay. Dr Hozack reviewed an impressive, single surgeon cohort of 3,977 DAA THAs and analyzed adverse events and 90 day perioperative outcomes. Simultaneous bilateral DAA THA was comparable with unilateral or staged bilateral procedures in regards to complications, readmission rate and home discharge rate but with an increased risk of transfusion. To examine the risk of complications with outpatient joint arthroplasty, Dr Della Valle performed a single-surgeon matched cohort analysis comparing outpatient and inpatient hip and knee arthroplasties. Outpatient procedures were not associated with an increased risk of any postoperative complications and actually experienced fewer emergency department visits. The eighth session covered various contemporary challenges in hip arthroplasty care. Dr Griffin began the session with an analysis of the timing of complications associated with two-stage exchange procedures for periprosthetic joint infection (PJI). Of the 189 hips included, 41.6% had a complication and the mortality was 14.1% at 2.5 years, highlighting the morbidity of this treatment method. Dr Fehring provided data assessing the fate of two-stage reimplantation after failed debridement, antibiotics and implant retention (DAIR) for a prosthetic hip infection. This analysis of 114 hips yielded concerning results demonstrating a 42.9% treatment failure of patients treated with a previous DAIR compared to a 12.3% failure rate in patients treated with an initial 2-stage procedure. Dr Jacobs reviewed the analysis of 106 femoral heads with severe corrosion and identified a chemically dominated etching process termed “column damage” to be a detrimental damage mode within CoCr femoral heads that is directly linked to banding within its microstructure. These data indicate that implant alloy microstructure must be optimized to minimize the release of fretting-corrosion products. Simon Mears presented retrospective data from 184 THAs with a dual modular femoral stem. A subgroup of hips with a modular, cobalt chromium femoral neck had a pseudotumor visualized in 15% with only 55% of these having elevated CoCr levels. These findings may support the use of routine follow-up MARS MRI for modular CoCr femoral neck prostheses. The final two studies explored timely issues related to viral illness and hip surgery. Dr Browne analyzed three large administrative databases to elucidate whether patients are at increased risk for viral illnesses following total joint replacement. The incidence of postoperative influenza after total joint replacement was not increased compared to patients not undergoing total joint replacement surgery suggesting that arthroplasty procedures may not heighten the risk of viral illness. In the final paper of the session Dr Haddad presented important data regarding perioperative complications in coronavirus positive patients undergoing surgical treatment of femoral neck fractures. In this multicenter cohort study from the United Kingdom 82 coronavirus positive patients were shown to have longer hospital stays, more critical care unit admissions, higher risk of perioperative complications and an increased mortality compared to 340 coronavirus negative patients. The eighth session had two papers on alternative femoral stem designs and three presentations more focused on femoral fracture treatments. Dr Mihalko focused on the European and US experiences with the Metha femoral neck retaining stem. The US experience mirrored the encouraging results from Europe with a 94% all cause femoral survivorship and a 99.1% femoral aseptic loosening survivorship at 5 years. Dr Kraay summarized dual energy x-ray absorptiometry (DEXA) evaluation of 16 low modulus composite femoral components at long-term follow-up of a mean 22 years. The bone mineral density associated with the implant increased in Gruen zones 2–6 and showed limited decreases in zones 1 and 7. These data support the concept that a low modulus femoral stem may more effectively load the proximal femur. Dr Springer provided data from the American Joint Replacement Registry (AJRR) and by evaluating outcomes of exact matched cohorts of 17,138 patients treated with cementless or cemented femoral implants for femoral neck fractures. Cemented implants were associated with marked reduction in early revision and periprosthetic fractures. However, cemented fixation was associated with an increased mortality at 90 days and 1 year. Additional data from the AJRR was presented by Dr Huddleston who investigated the risk factors for revision surgery after arthroplasty in a cohort of 75,333 femoral neck fractures. THA when compared to hemiarthroplasty was associated with higher early and overall revision rates. Cementless femoral fixation and increased age were also associated with higher rates of any revision. Both of these studies from the AJRR suggest that further consideration should be given to femoral fixation preferences in the femoral neck fracture population. Dr Vail summarized his institution's experience with an interdisciplinary hip fracture protocol for patients undergoing arthroplasty for acute femoral neck fractures. His study compared 157 cases prior to protocol implementation with 114 patients treated after the protocol was established. The impact of the interdisciplinary protocol was impressive as evidenced by a reduced time to operative treatment, length of stay, complication rate and one-year mortality. All being achieved without an increase in readmissions or facility discharges. The final session of the meeting addressed innovations in perioperative care of THA patients. Dr Barrack started the session with an interesting study examining the feasibility and patient preferences regarding telemedicine. A cross-sectional telephone survey of 163 arthroplasty patients indicated that 88% of patients use the internet and 94% own a device capable of videoconferencing. Nevertheless, only 18% of patients preferred a video visit over an in-person clinic visit due to concerns of inferior care. Dr Barnes quantified preoperative optimization work in 100 arthroplasty patients by using EMR activity logs and determined the surgical team spends an average 75 minutes per case on preoperative work activities. Dr Duwelius reported the early outcomes of primary THA with a smartphone-based exercise and educational platform compared to standard of care controls. A randomized control trial design with 365 patients demonstrated similar outcomes and non-inferiority of the smartphone platform relative to complications, readmissions, emergency room/urgent care visits. The association of controlled substance use with THA outcomes was assessed by Dr Higuera Rueda. A quantitative assessment using the NarxCare score identified 300 and above as a score associated with adverse outcomes after THA. Dr Macaulay reviewed data from a large retrospective study of 1,825 THAs indicating that discontinuation of intermittent pneumatic compression devices does not increase the risk of venous thromboembolism in standard risk patients being treated with 81mg ASA BID as prophylaxis. Dr Antoniou presented the final paper of the meeting investigating potential changes in patient health status as an indication for surgery over time. Data from this large systematic review of the literature found patients undergoing THA at similar health status to the past with no influence form patient age, gender, year of enrollment or geographic region. As summarized above, the 2020 virtual Hip Society Summer Meeting was rich in scientific content, productive discussion and a collaborative spirit. This collective body of work will result in impactful scientific contributions and will serve as a foundation for future innovation and advancements in the treatment of hip disease

Aims

Current treatments of prosthetic joint infection (PJI) are minimally effective against Staphylococcus aureus biofilm. A murine PJI model of debridement, antibiotics, and implant retention (DAIR) was used to test the hypothesis that PlySs2, a bacteriophage-derived lysin, can target S. aureus biofilm and address the unique challenges presented in this periprosthetic environment.