The outcome of revision total hip arthroplasty for instability.

Aims: Instability is a common indication for revision total hip arthroplasty (THA). However, even after the initial revision, some patients continue to have recurrent dislocation. The aim of this study was to assess the risk for recurrent dislocation after revision THA for instability. Methods: Between 2009 and 2019, 163 patients underwent revision THA for instability at Stanford University Medical Center. Of these, 33 (20.2%) required re-revision due to recurrent dislocation. Cox proportional hazard models, with death and re-revision surgery for periprosthetic infection as competing events, were used to analyze the risk factors, including the size and alignment of the components. Paired t-tests or Wilcoxon signed-rank tests were used to assess the outcome using the Veterans RAND 12 (VR-12) physical and VR-12 mental scores, the Harris Hip Score (HHS) pain and function, and the Hip disability and Osteoarthritis Outcome score for Joint Replacement (HOOS, JR). Results: The median follow-up was 3.1 years (interquartile range 2.0 to 5.1). The one-year cumulative incidence of recurrent dislocation after revision was 8.7%, which increased to 18.8% at five years and 31.9% at ten years postoperatively. In multivariable analysis, a high American Society of Anesthesiologists (ASA) grade (hazard ratio (HR) 2.72 (95% confidence interval (CI) 1.13 to 6.60)), BMI between 25 and 30 kg/m2 (HR 4.31 (95% CI 1.52 to 12.27)), the use of specialized liners (HR 5.39 (95% CI 1.97 to 14.79) to 10.55 (95% CI 2.27 to 49.15)), lumbopelvic stiffness (HR 6.03 (95% CI 1.80 to 20.23)), and postoperative abductor weakness (HR 7.48 (95% CI 2.34 to 23.91)) were significant risk factors for recurrent dislocation. Increasing the size of the acetabular component by > 1 mm significantly decreased the risk of dislocation (HR 0.89 (95% CI 0.82 to 0.96)). The VR-12 physical and HHS (pain and function) scores improved significantly at mid term. Conclusion: Patients requiring revision THA for instability are at risk of recurrent dislocation. Higher ASA grades, being overweight, a previous lumbopelvic fusion, the use of specialized liners, and postoperative abductor weakness are significant risk factors.

Targeting an inflammation-amplifying cell population can attenuate osteoarthritis-associated pain.

BACKGROUND: Understanding of pain in osteoarthritis, its genesis, and perception is still in its early stages. Identification of precise ligand-receptor pairs that transduce pain and the cells and tissues in which they reside will elucidate new therapeutic approaches for pain management. Our recent studies had identified an inflammation-amplifying (Inf-A) cell population that is expanded in human OA cartilage and is distinctive in the expression of both IL1R1 and TNF-R2 receptors and active Jnk signaling cascade. METHODS: In this study, we have tested the function of the cartilage-resident IL1R1+TNF-R2+ Inf-A cells in OA. We have identified that the IL1R1+TNF-R2+ Inf-A cells expand in aged mice as well as after anterior cruciate ligament tear upon tibia loading and OA initiation in mice. We targeted and modulated the Jnk signaling cascade in InfA through competitive inhibition of Jnk signaling in mice and human OA explants and tested the effects on joint structure and gait in mice. RESULTS: Modulation of Jnk signaling led to attenuation of inflammatory cytokines CCL2 and CCL7 without showing any structural improvements in the joint architecture. Interestingly, Jnk inhibition and lowered CCL2 and 7 are sufficient to significantly improve the gait parameters in treated PTOA mice demonstrating reduced OA-associated pain. Consistent with the mice data, treatment with JNK inhibitor did not improve human OA cartilage explants. CONCLUSION: These studies demonstrate that Inf-A, an articular-cartilage resident cell population, contributes to pain in OA via secretion of CCL2 and 7 and can be targeted via inhibition of Jnk signaling.

Preclinical models for studying corticosteroid-induced osteonecrosis of the femoral head.

Nontraumatic osteonecrosis of the femoral head (ONFH) is a refractory condition that commonly results in femoral head collapse and degenerative arthritis of the hip. In the early stages, surgical procedures for hip preservation, including core decompression (CD), have been developed to prevent progressive collapse of the femoral head. Optimization of bone regeneration and biological augmentation may further enhance the therapeutic efficacy of CD for ONFH. Thus, combining CD with cell-based therapy has recently been proposed. In fact, patients treated with cell-based therapy using autologous bone marrow concentrate demonstrate improved survivorship of the femoral head, compared with conventional CD alone. Preclinical research studies to investigate adjunctive therapies for CD often utilize the rabbit model of corticosteroid-induced ONFH. Mesenchymal stem cells (MSCs) are known to promote osteogenesis and angiogenesis, and decrease inflammation in bone. Local drug delivery systems have the potential to achieve targeted therapeutic effects by precisely controlling the drug release rate. Scaffolds can provide an osteoconductive structural framework to facilitate the repair of osteonecrotic bone tissue. We focused on the combination of both cell-based and scaffold-based therapies for bone tissue regeneration in ONFH. We hypothesized that combining CD and osteoconductive scaffolds would provide mechanical strength and structural cell guidance; and that combining CD and genetically modified (GM) MSCs to express relevant cytokines, chemokines, and growth factors would promote bone tissue repair. We developed GM MSCs that overexpress the anti-inflammatory, pro-reconstructive cytokines platelet-derived growth factor-BB to provide MSCs with additional benefits and investigated the efficacy of combinations of these GM MSCs and scaffolds for treatment of ONFH in skeletally mature male New Zealand white rabbits. In the future, the long-term safety, efficacy, durability, and cost-effectiveness of these and other biological and mechanical treatments must be demonstrated for the patients affected by ONFH.

TET1 Regulates Skeletal Stem-Cell Mediated Cartilage Regeneration.

OBJECTIVE: Adult skeletal stem cells (SSCs) that give rise to chondrocytes, osteocytes, and stromal cells as progeny have been shown to contribute to cartilage regeneration in osteoarthritis (OA). Understanding extrinsic and intrinsic regulators of SSC fate and function can therefore identify putative candidate factors to enhance cartilage regeneration. This study explores how the DNA hydroxymethylase Tet1 regulates SSC function in OA. METHODS: We investigated the differences in the SSC lineage tree and differentiation potential in neonatal and adult Tet1+/+ and Tet1-/- mice with and without injury and upon OA induction and progression. Using RNA sequencing, the transcriptomic differences between SSCs and bone cartilage stroma progenitor cells (BCSPs) were identified in Tet1+/+ mice and Tet1-/- mice. RESULTS: Loss of Tet1 skewed the SSC lineage tree by expanding the SSC pool and enhanced the chondrogenic potential of SSCs and BCSPs. Tet1 inhibition led to enhanced chondrogenesis in human SSCs and chondroprogenitors isolated from human cartilage. Importantly, TET1 inhibition in vivo in late stages of a mouse model of OA led to increased cartilage regeneration. Transcriptomic analyses of SSCs and BCSPs lacking Tet1 revealed pathway alterations in transforming growth factor ß signaling, melatonin degradation, and cartilage development-associated genes. Lastly, we report that use of the hormone melatonin can dampen inflammation and improve cartilage health. CONCLUSION: Although Tet1 is a broad epigenetic regulator, melatonin can mimic the inhibition ability of TET1 to enhance the chondrogenic ability of SSCs. Melatonin administration has the potential to be an attractive stem cell-based therapy for cartilage regeneration.

Host and microbial characteristics associated with recurrent prosthetic joint infections.

Approximately 20% of patients after resection arthroplasty and antibiotic spacer placement for prosthetic joint infection develop repeat infections, requiring an additional antibiotic spacer before definitive reimplantation. The host and bacterial characteristics associated with the development of recurrent infection is poorly understood. A case-control study was conducted for 106 patients with intention to treat by two-stage revision arthroplasty for prosthetic joint infection at a single institution between 2009 and 2020. Infection was defined according to the 2018 Musculoskeletal Infection Society criteria. Thirty-nine cases ("recurrent-periprosthetic joint infection [PJI]") received at least two antibiotic spacers before clinical resolution of their infection, and 67 controls ("single-PJI") received a single antibiotic cement spacer before infection-free prosthesis reimplantation. Patient demographics, McPherson host grade, and culture results including antibiotic susceptibilities were compared. Fifty-two (78%) single-PJI and 32 (82%) recurrent-PJI patients had positive intraoperative cultures at the time of their initial spacer procedure. The odds of polymicrobial infections were 11-fold higher among recurrent-PJI patients, and the odds of significant systemic compromise (McPherson host-grade C) were more than double. Recurrent-PJI patients were significantly more likely to harbor Staphylococcus aureus. We found no differences between cases and controls in pathogen resistance to the six most tested antibiotics. Among recurrent-PJI patients, erythromycin-resistant infections were more prevalent at the final than initial spacer, despite no erythromycin exposure. Our findings suggest that McPherson host grade, polymicrobial infection, and S. aureus infection are key indicators of secondary or persistent joint infection following resection arthroplasty and antibiotic spacer placement, while bacterial resistance does not predict infection-related arthroplasty failure.

Primary Total Hip Arthroplasty in Juvenile Idiopathic Arthritis: Survivorship After a Median Follow-Up of 12 Years.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is a chronic inflammatory condition of childhood that frequently affects the hip. Total hip arthroplasty (THA) in JIA can be challenging due to the patient's young age, small proportion, complex anatomy, and bone loss. Outcome data are limited. METHODS: We reviewed prospectively collected data in 57 JIA patients (83 hips) who underwent THA between 1986 and 2020 by a single surgeon. The median patient age at surgery was 26 years (range, 14 to 62). Reoperation-free survival was assessed via the cumulative incidence function, accounting for the competing risk of death. Relationships between patient and implant factors and survivorship were evaluated by stratification of the cumulative incidence function and Gray's tests. Wilcoxon signed rank tests were used to assess the preoperative to latest postoperative change in patient-reported outcome measures. RESULTS: At a median (interquartile range) of 12 (4, 20) years of follow-up, 13 (16%) patients underwent reoperation, most commonly for polyethylene wear and osteolysis (7 hips). The estimated incidence of 10-year, 20-year, and 30-year revision (95% confidence interval) were 11.3% (4.5, 21.6%), 18.5% (8.9, 30.9%), and 40.6% (19.4, 60.9%), respectively. There were no differences in survival based on patient age, sex, implant fixation method, polyethylene type, or thickness. All patient-reported outcome measures improved from preoperative to latest follow-up. CONCLUSIONS: Primary THA is a durable and effective treatment for JIA patients with severe hip involvement and results in major improvements in pain and function. We did not identify any factors predictive of failure.

The 2023 Orthopaedic Research Society's International Consensus Meeting on musculoskeletal infection: Summary from the host immunity section.

Musculoskeletal infections (MSKI), which are a major problem in orthopedics, occur when the pathogen eludes or overwhelms the host immune system. While effective vaccines and immunotherapies to prevent and treat MSKI should be possible, fundamental knowledge gaps in our understanding of protective, nonprotective, and pathogenic host immunity are prohibitive. We also lack critical knowledge of how host immunity is affected by the microbiome, implants, prior infection, nutrition, antibiotics, and concomitant therapies, autoimmunity, and other comorbidities. To define our current knowledge of these critical topics, a Host Immunity Section of the 2023 Orthopaedic Research Society MSKI International Consensus Meeting (ICM) proposed 78 questions. Systematic reviews were performed on 15 of these questions, upon which recommendations with level of evidence were voted on by the 72 ICM delegates, and another 12 questions were voted on with a recommendation of "Unknown" without systematic reviews. Two questions were transferred to another ICM Section, and the other 45 were tabled for future consideration due to limitations of available human resources. Here we report the results of the voting with internet access to the questions, recommendations, and rationale from the systematic reviews. Eighteen questions received a consensus vote of ≥90%, while nine recommendations failed to achieve this threshold. Commentary on why consensus was not achieved on these questions and potential ways forward are provided to stimulate specific funding mechanisms and research on these critical MSKI host defense questions.

C-C Motif Chemokine Ligand 2 Enhances Macrophage Chemotaxis, Osteogenesis, and Angiogenesis during the Inflammatory Phase of Bone Regeneration.

Local cell therapy has recently gained attention for the treatment of joint diseases and fractures. Mesenchymal stem cells (MSCs) are not only involved in osteogenesis and angiogenesis, but they also have immunomodulatory functions, such as inducing macrophage migration during bone regeneration via macrophage crosstalk. C-C motif chemokine ligand 2 (CCL2), a known inflammatory mediator, is associated with the migration of macrophages during inflammation. This study examined the utility of CCL2 as a therapeutic target for local cell therapy. Using lentiviral vectors for rabbit MSCs, genetically modified CCL2 overexpressing MSCs were generated. Osteogenic differentiation assays were performed using MSCs with or without macrophages in co-culture, and cell migration assays were also performed. Additionally, co-cultures were performed with endothelial cells (ECs), and angiogenesis was evaluated using a tube formation assay. Overexpression of CCL2 did not affect bone formation under monoculture conditions but promoted chemotaxis and osteogenesis when co-cultured with macrophages. Furthermore, CCL2-overexpression promoted tube formation in co-culture with ECs. These results suggest that CCL2 induces macrophage chemotaxis and osteogenesis by promoting crosstalk between MSCs and macrophages; CCL2 also stimulates ECs to induce angiogenesis. These findings indicate that CCL2 may be a useful therapeutic target for local cell therapy in areas of bone loss.

Glycolytic reprogramming in macrophages and MSCs during inflammation.

Background: Dysregulated inflammation is associated with many skeletal diseases and disorders, such as osteolysis, non-union of fractures, osteonecrosis, osteoarthritis and orthopaedic infections. We previously showed that continuous infusion of lipopolysaccharide (LPS) contaminated polyethylene particles (cPE) caused prolonged inflammation and impaired bone formation. However, the metabolic and bioenergetic processes associated with inflammation of bone are unknown. Mitochondria are highly dynamic organelles that modulate cell metabolism and orchestrate the inflammatory responses that involve both resident and recruited cells. Glycolytic reprogramming, the shift from oxidative phosphorylation (OXPHOS) to glycolysis causes inappropriate cell activation and function, resulting in dysfunctional cellular metabolism. We hypothesized that impaired immunoregulation and bone regeneration from inflammatory states are associated with glycolytic reprogramming and mitochondrial dysfunction in macrophages (Mφ) and mesenchymal stromal cells (MSCs). Methods: We used the Seahorse XF96 analyzer and real-time qPCR to study the bioenergetics of Mφ and MSCs exposed to cPE. To understand the oxygen consumption rate (OCR), we used Seahorse XF Cell Mito Stress Test Kit with Seahorse XF96 analyzer. Similarly, Seahorse XF Glycolytic Rate Assay Kit was used to detect the extracellular acidification rate (ECAR) and Seahorse XF Real-Time ATP Rate Assay kit was used to detect the real-time ATP production rates from OXPHOS and glycolysis. Real-time qPCR was performed to analyze the gene expression of key enzymes in glycolysis and mitochondrial biogenesis. We further detected the gene expression of proinflammatory cytokines in Mφ and genes related to cell differentiation in MSC during the challenge of cPE. Results: Our results demonstrated that the oxidative phosphorylation of Mφ exposed to cPE was significantly decreased when compared with the control group. We found reduced basal, maximal and ATP-production coupled respiration rates, and decreased proton leak in Mφ during challenge with cPE. Meanwhile, Mφ showed increased basal glycolysis and proton efflux rates (PER) when exposed to cPE. The percentage (%) of PER from glycolysis was higher in Mφ exposed to cPE, indicating that the contribution of the glycolytic pathway to total extracellular acidification was elevated during the challenge of cPE. In line with the results of OCR and ECAR, we found Mφ during cPE challenge showed higher glycolytic ATP (glycoATP) production rates and lower mitochondrial ATP (mitoATP) production rates which is mainly from OXPHOS. Interestingly, MSCs showed enhanced glycolysis during challenge with cPE, but no significant changes in oxygen consumption rates (OCR). In accordance, seahorse assay of real-time ATP revealed glycoATP rates were elevated while mitoATP rates showed no significant differences in MSC during challenge with cPE. Furthermore, Mφ and MSCs exposed to cPE showed upregulated gene expression levels of glycolytic regulators and Mφ exposed to cPE expressed higher levels of pro-inflammatory cytokines. Conclusion: This study demonstrated the dysfunctional bioenergetic activity of bone marrow-derived Mφ and MSCs exposed to cPE, which could impair the immunoregulatory properties of cells in the bone niche. The underlying molecular defect related to disordered mitochondrial function could represent a potential therapeutic target during the resolution of inflammation.

Selecting a high-dose antibiotic-laden cement knee spacer.

Prosthetic joint infection [PJI] after total knee arthroplasty (TKA) remains a common and challenging problem for joint replacement surgeons and patients. Once the diagnosis of PJI has been made, patient goals and characteristics as well as the infection timeline dictate treatment. Most commonly, this involves a two-stage procedure with the removal of all implants, debridement, and placement of a static or dynamic antibiotic spacer. Static spacers are commonly indicated for older, less healthy patients that would benefit from soft tissue rest after initial debridement. Mobile spacers are typically used in younger, healthier patients to improve quality of life and reduce soft-tissue contractures during antibiotic spacer treatment. Spacers are highly customizable with regard to antibiotic choice, cement variety, and spacer design, each with reported advantages, drawbacks, and indications that will be covered in this article. While no spacer is superior to any other, the modern arthroplasty surgeon must be familiar with the available modalities to optimize treatment for each patient. Here we propose a treatment algorithm to assist surgeons in deciding on treatment for PJI after TKA.

MegaPro, a clinically translatable nanoparticle for in vivo tracking of stem cell implants in pig cartilage defects.

Rationale: Efficient labeling methods for mesenchymal stem cells (MSCs) are crucial for tracking and understanding their behavior in regenerative medicine applications, particularly in cartilage defects. MegaPro nanoparticles have emerged as a potential alternative to ferumoxytol nanoparticles for this purpose. Methods: In this study, we employed mechanoporation to develop an efficient labeling method for MSCs using MegaPro nanoparticles and compared their effectiveness with ferumoxytol nanoparticles in tracking MSCs and chondrogenic pellets. Pig MSCs were labeled with both nanoparticles using a custom-made microfluidic device, and their characteristics were analyzed using various imaging and spectroscopy techniques. The viability and differentiation capacity of labeled MSCs were also assessed. Labeled MSCs and chondrogenic pellets were implanted into pig knee joints and monitored using MRI and histological analysis. Results: MegaPro-labeled MSCs demonstrated shorter T2 relaxation times, higher iron content, and greater nanoparticle uptake compared to ferumoxytol-labeled MSCs, without significantly affecting their viability and differentiation capacity. Post-implantation, MegaPro-labeled MSCs and chondrogenic pellets displayed a strong hypointense signal on MRI with considerably shorter T2* relaxation times compared to adjacent cartilage. The hypointense signal of both MegaPro- and ferumoxytol-labeled chondrogenic pellets decreased over time. Histological evaluations showed regenerated defect areas and proteoglycan formation with no significant differences between the labeled groups. Conclusion: Our study demonstrates that mechanoporation with MegaPro nanoparticles enables efficient MSC labeling without affecting viability or differentiation. MegaPro-labeled cells show enhanced MRI tracking compared to ferumoxytol-labeled cells, emphasizing their potential in clinical stem cell therapies for cartilage defects.

Metabolic profile of mesenchymal stromal cells and macrophages in the presence of polyethylene particles in a 3D model.

BACKGROUND: Continuous cross talk between MSCs and macrophages is integral to acute and chronic inflammation resulting from contaminated polyethylene particles (cPE); however, the effect of this inflammatory microenvironment on mitochondrial metabolism has not been fully elucidated. We hypothesized that (a) exposure to cPE leads to impaired mitochondrial metabolism and glycolytic reprogramming and (b) macrophages play a key role in this pathway. METHODS: We cultured MSCs with/without uncommitted M0 macrophages, with/without cPE in 3-dimensional gelatin methacrylate (3D GelMA) constructs/scaffolds. We evaluated mitochondrial function (membrane potential and reactive oxygen species-ROS production), metabolic pathways for adenosine triphosphate (ATP) production (glycolysis or oxidative phosphorylation) and response to stress mechanisms. We also studied macrophage polarization toward the pro-inflammatory M1 or the anti-inflammatory M2 phenotype and the osteogenic differentiation of MSCs. RESULTS: Exposure to cPE impaired mitochondrial metabolism of MSCs; addition of M0 macrophages restored healthy mitochondrial function. Macrophages exposed to cPE-induced glycolytic reprogramming, but also initiated a response to this stress to restore mitochondrial biogenesis and homeostatic oxidative phosphorylation. Uncommitted M0 macrophages in coculture with MSC polarized to both M1 and M2 phenotypes. Osteogenesis was comparable among groups after 21 days. CONCLUSION: This work confirmed that cPE exposure triggers impaired mitochondrial metabolism and glycolytic reprogramming in a 3D coculture model of MSCs and macrophages and demonstrated that macrophages cocultured with MSCs undergo metabolic changes to maintain energy production and restore homeostatic metabolism.

Assessment of Team Dynamics and Operative Efficiency in Hip and Knee Arthroplasty.

Importance: Surgical team communication is a critical component of operative efficiency. The factors underlying optimal communication, including team turnover, role composition, and mutual familiarity, remain underinvestigated in the operating room. Objective: To assess staff turnover, trainee involvement, and surgeon staff preferences in terms of intraoperative efficiency. Design, Setting, and Participants: Retrospective analysis of staff characteristics and operating times for all total joint arthroplasties was performed at a tertiary academic medical center by 5 surgeons from January 1 to December 31, 2018. Data were analyzed from May 1, 2021, to February 18, 2022. The study included cases with primary total hip arthroplasties (THAs) and primary total knee arthroplasties (TKAs) comprising all primary total joint arthroplasties performed over the 1-year study interval. Exposures: Intraoperative turnover among nonsurgical staff, presence of trainees, and presence of surgeon-preferred staff. Main Outcomes and Measures: Incision time, procedure time, and room time for each surgery. Multivariable regression analyses between operative duration, presence of surgeon-preferred staff, and turnover among nonsurgical personnel were conducted. Results: A total of 641 cases, including 279 THAs (51% female; median age, 64 [IQR, 56.3-71.5] years) and 362 TKAs (66% [238] female; median age, 68 [IQR, 61.1-74.1] years) were considered. Turnover among circulating nurses was associated with a significant increase in operative duration in both THAs and TKAs, with estimated differences of 19.6 minutes (SE, 3.5; P < .001) of room time in THAs and 14.0 minutes (SE, 3.1; P < .001) of room time in TKAs. The presence of a preferred anesthesiologist or surgical technician was associated with significant decreases of 26.5 minutes (SE, 8.8; P = .003) of procedure time and 12.6 minutes (SE, 4.0; P = .002) of room time, respectively, in TKAs. The presence of a surgeon-preferred vendor was associated with a significant increase in operative duration in both THAs (26.3 minutes; SE, 7.3; P < .001) and TKAs (29.6 minutes; SE, 9.6; P = .002). Conclusions and Relevance: This study found that turnover among operative staff is associated with procedural inefficiency. In contrast, the presence of surgeon-preferred staff may facilitate intraoperative efficiency. Administrative or technologic support of perioperative communication and team continuity may help improve operative efficiency.

The efficiency of genetically modified mesenchymal stromal cells combined with a functionally graded scaffold for bone regeneration in corticosteroid-induced osteonecrosis of the femoral head in rabbits.

Core decompression (CD) with mesenchymal stromal cells (MSCs) is an effective therapy for early-stage osteonecrosis of the femoral head (ONFH). Preconditioning of MSCs, using inflammatory mediators, is widely used in immunology and various cell therapies. We developed a three-dimensional printed functionally graded scaffold (FGS), made of ß-TCP and PCL, for cell delivery at a specific location. The present study examined the efficacy of CD treatments with genetically modified (GM) MSCs over-expressing PDGF-BB (PDGF-MSCs) or GM MSCs co-over-expressing IL-4 and PDGF-BB and preconditioned for three days of exposure to lipopolysaccharide and tumor necrosis factor-alpha (IL-4-PDGF-pMSCs) using the FGS for treating steroid-induced ONFH in rabbits. We compared CD without cell-therapy, with IL-4-PDGF-pMSCs alone, and with FGS loaded with PDGF-MSCs or IL-4-PDGF-pMSCs. For the area inside the CD, the bone volume in the CD alone was higher than in both FGS groups. The IL-4-PDGF-pMSCs alone and FGS + PDGF-MSCs reduced the occurrence of empty lacunae and improved osteoclastogenesis. There was no significant difference in angiogenesis among the four groups. The combined effect of GM MSCs or pMSCs and the FGS was not superior to the effect of each alone. To establish an important adjunctive therapy for CD for early ONFH in the future, it is necessary and essential to develop an FGS that delivers biologics appropriately and provides structural and mechanical support.

Objective Activity Parameters Track Patient-specific Physical Recovery Trajectories After Surgery and Link With Individual Preoperative Immune States.

OBJECTIVE: The longitudinal assessment of physical function with high temporal resolution at a scalable and objective level in patients recovering from surgery is highly desirable to understand the biological and clinical factors that drive the clinical outcome. However, physical recovery from surgery itself remains poorly defined and the utility of wearable technologies to study recovery after surgery has not been established. BACKGROUND: Prolonged postoperative recovery is often associated with long-lasting impairment of physical, mental, and social functions. Although phenotypical and clinical patient characteristics account for some variation of individual recovery trajectories, biological differences likely play a major role. Specifically, patient-specific immune states have been linked to prolonged physical impairment after surgery. However, current methods of quantifying physical recovery lack patient specificity and objectivity. METHODS: Here, a combined high-fidelity accelerometry and state-of-the-art deep immune profiling approach was studied in patients undergoing major joint replacement surgery. The aim was to determine whether objective physical parameters derived from accelerometry data can accurately track patient-specific physical recovery profiles (suggestive of a 'clock of postoperative recovery'), compare the performance of derived parameters with benchmark metrics including step count, and link individual recovery profiles with patients' preoperative immune state. RESULTS: The results of our models indicate that patient-specific temporal patterns of physical function can be derived with a precision superior to benchmark metrics. Notably, 6 distinct domains of physical function and sleep are identified to represent the objective temporal patterns: ''activity capacity'' and ''moderate and overall activity (declined immediately after surgery); ''sleep disruption and sedentary activity (increased after surgery); ''overall sleep'', ''sleep onset'', and ''light activity'' (no clear changes were observed after surgery). These patterns can be linked to individual patients preopera-tive immune state using cross-validated canonical-correlation analysis. Importantly, the pSTAT3 signal activity in monocytic myeloid-derived suppressor cells predicted a slower recovery. CONCLUSIONS: Accelerometry-based recovery trajectories are scalable and objective outcomes to study patient-specific factors that drive physical recovery.

Revision Hip Arthroplasty Using a Modular, Cementless Femoral Stem: Long-Term Follow-Up.

BACKGROUND: As the number of primary total hip arthroplasty (THA) cases increase, so does the demand for revision operations. However, long-term follow-up data for revision THA is lacking. METHODS: A retrospective review was completed of patients who underwent revision THA at a single institution between January 2002 and October 2007 using a cementless modular stem. Patient demographic, clinical, and radiographic data was collected. Preoperative and postoperative patient-reported outcome scores were compared at a minimum of fourteen-year follow-up. RESULTS: Eighty-four patients (89 hips) with a median age of 69 years (range, 28 to 88) at operation were included. Indications for revision included aseptic loosening (84.2%), infection (12.4%), and periprosthetic fracture (3.4%). Twenty-two hips sustained at least 1 complication: intraoperative fracture (7.9%), dislocation (6.7%), prosthetic joint infection (4.5%), deep venous thrombosis (3.4%), and late periprosthetic fracture (2.2%). There were no modular junction complications. Eight patients underwent reoperations; only three involved the stem. Thirty-eight patients (45%) were deceased prior to final follow-up without known reoperations. Twenty-seven patients (32%) were lost to follow-up. Twenty-one patients (23%) were alive at minimum fourteen-year follow-up. Complete patient-reported outcomes were available for nineteen patients (range, 14 to 18.5 years of follow-up). Significant improvement was seen in UCLA activity, VR-12 physical, hip disability and osteoarthritis outcome score, joint replacement., and Harris Hip score pain and function scores. CONCLUSION: Challenges of long-term follow-up include patient migration, an unwillingness to travel for re-examination, medical comorbidities, advanced age, and death. The cementless modular revision stem demonstrated long-term clinical success and remains a safe and reliable option for complex revision operations.

The Environmental Impact of Orthopaedic Surgery.

➤: There are a growing number of opportunities within the field of orthopaedic surgery to address climate change and investigate ways to promote sustainability. ➤: Orthopaedic surgeons can take a proactive role in addressing climate change and its impacts within the areas of operating-room waste, carbon emissions from transportation and implant manufacturing, anesthetic gases, and water usage. ➤: Future studies are needed to further these initiatives on quantifying and decreasing environmental impact and furthering sustainable use of our resources.

Outcome of the Wagner Cone femoral component for difficult anatomical conditions during total hip arthroplasty.

PURPOSE: Total hip arthroplasty (THA) in patients with small or unusual proximal femoral anatomy is challenging due to sizing issues, control of version, and implant fixation. The Wagner Cone is a monoblock, fluted, tapered stem with successful outcomes for these patients; however, there is limited information on subsidence, a common finding with cementless stems. METHODS: We retrospectively reviewed our cases using the modified Wagner Cone (Zimmer, Warsaw, IN) implanted over a 13-year period (2006-2019) in patients with small or abnormal proximal femoral anatomy. We performed 144 primary THAs in 114 patients using this prosthesis. Mean follow-up was 4.5 ± 3.4 years (range, 1-13 years). Common reasons for implantation were hip dysplasia (52%) and osteoarthritis in patients with small femoral proportions (22%). Analysis of outcomes included assessment of stem subsidence and stability. RESULTS: Survival was 98.6% in aseptic cases; revision-free survival was 97.9%. Femoral subsidence occurred in 84 cases (58%). No subsidence progressed after 3 months. Of those that subsided, the mean distance was 2.8 ± 2.0 mm. There was less subsidence in stems that stabilized prior to six weeks (2.2 ± 1.4 mm) compared to those that continued until 12 weeks (3.9 ± 1.6, p = 0.02). Harris Hip, UCLA, and WOMAC scores significantly improved from pre-operative evaluation (p < 0.001*, p < 0.003*, p ≪ 0.001*); there was no difference in outcome between patients with and without subsidence (p = 0.430, p = 0.228, p = 0.147). CONCLUSION: The modified Wagner Cone demonstrates excellent clinical outcomes in patients with challenging proximal femoral anatomy. Subsidence is minor, stops by 3 months, and does not compromise clinical outcome.

Isolated Versus Full Component Revision in Total Knee Arthroplasty for Aseptic Loosening.

BACKGROUND: Revision of both femoral and tibial components of a total knee arthroplasty (TKA) for aseptic loosening has favorable outcomes. Revision of only one loose component with retention of others has shorter operative time and lower cost; however, implant survivorship and clinical outcomes of these different operations are unclear. METHODS: Between January 2009 and December 2019, a consecutive cohort of revision TKA was reviewed. Univariate and multivariable analyses were used to study correlations among factors and surgical related complications, time to prosthesis failure, and functional outcomes (University of California Los Angeles, Knee Society functional, knee osteoarthritis and outcome score for joint replacement, Veterans RAND 12 (VR-12) physical, and VR-12 mental). RESULTS: A total of 238 patients underwent revision TKA for aseptic loosening. The mean follow-up time was 61 months (range 25 to 152). Ten of the 105 patients (9.5%) who underwent full revision (both femoral and tibial components) and 18 of the 133 (13.5%) who underwent isolated revision had subsequent prosthesis failure [Hazard ratio (HR) 0.67, P = .343]. The factor analysis of type of revision (full or isolated revision) did not demonstrate a significant difference between groups in terms of complications, implant failures, and times to failure. Metallosis was related to early time to failure [Hazard ratio 10.11, P < .001] and iliotibial band release was associated with more complications (Odds ratio 9.87, P = .027). Preoperative symptoms of instability were associated with the worst improvement in University of California Los Angeles score. Higher American Society of Anesthesiologists status and higher Charlson Comorbidity Index were related with worse VR-12 physical (-30.5, P = .008) and knee osteoarthritis and outcome score for joint replacement (-4.2, P = .050) scores, respectively. CONCLUSION: Isolated and full component revision TKA for aseptic loosening does not differ with respect to prosthesis failures, complications, and clinical results at 5 years. Poor American Society of Anesthesiologists status, increased comorbidities, instability, and a severe bone defect are related to worse functional improvement. LEVEL OF EVIDENCE: III, cohort with control.

Therapeutic effects of MSCs, genetically modified MSCs, and NFĸB-inhibitor on chronic inflammatory osteolysis in aged mice.

The number of total joint replacements is increasing, especially in elderly patients, and so too are implant-related complications such as prosthesis loosening. Wear particles from the prosthesis induce a chronic inflammatory reaction and subsequent osteolysis, leading to the need for revision surgery. This study investigated the therapeutic effect of NF-ĸB decoy oligodeoxynucleotides (ODN), mesenchymal stem cells (MSCs), and genetically-modified NF-ĸB sensing interleukin-4 over-secreting MSCs (IL4-MSCs) on chronic inflammation in aged mice. The model was generated by continuous infusion of contaminated polyethylene particles into the intramedullary space of the distal femur of aged mice (15-17 months old) for 6 weeks. Local delivery of ODN showed increased bone mineral density (BMD), decreased osteoclast-like cells, increased alkaline phosphatase (ALP)-positive area, and increased M2/M1 macrophage ratio. Local injection of MSCs and IL4-MSCs significantly decreased osteoclast-like cells and increased the M2/M1 ratio, with a greater trend for IL4-MSCs than MSCs. MSCs significantly increased ALP-positive area and BMD values compared with the control. The IL4-MSCs demonstrated higher values for both ALP-positive area and BMD. These findings demonstrated the therapeutic effects of ODN, MSCs, and IL4-MSCs on chronic inflammatory osteolysis in aged mice. The two MSC-based therapies were more effective than ODN in increasing the M2/M1 macrophage ratio, reducing bone resorption, and increasing bone formation. Specifically, MSCs were more effective in increasing bone formation, and IL4-MSCs were more effective in mitigating inflammation. This study suggests potential therapeutic strategies for treating wear particle-associated inflammatory osteolysis after arthroplasty in the elderly.