Identification of the Human Skeletal Stem Cell.

Stem cell regulation and hierarchical organization of human skeletal progenitors remain largely unexplored. Here, we report the isolation of a self-renewing and multipotent human skeletal stem cell (hSSC) that generates progenitors of bone, cartilage, and stroma, but not fat. Self-renewing and multipotent hSSCs are present in fetal and adult bones and can also be derived from BMP2-treated human adipose stroma (B-HAS) and induced pluripotent stem cells (iPSCs). Gene expression analysis of individual hSSCs reveals overall similarity between hSSCs obtained from different sources and partially explains skewed differentiation toward cartilage in fetal and iPSC-derived hSSCs. hSSCs undergo local expansion in response to acute skeletal injury. In addition, hSSC-derived stroma can maintain human hematopoietic stem cells (hHSCs) in serum-free culture conditions. Finally, we combine gene expression and epigenetic data of mouse skeletal stem cells (mSSCs) and hSSCs to identify evolutionarily conserved and divergent pathways driving SSC-mediated skeletogenesis. VIDEO ABSTRACT.

Deficient Activity of the Nuclease MRE11A Induces T Cell Aging and Promotes Arthritogenic Effector Functions in Patients with Rheumatoid Arthritis.

Immune aging manifests with a combination of failing adaptive immunity and insufficiently restrained inflammation. In patients with rheumatoid arthritis (RA), T cell aging occurs prematurely, but the mechanisms involved and their contribution to tissue-destructive inflammation remain unclear. We found that RA CD4+ T cells showed signs of aging during their primary immune responses and differentiated into tissue-invasive, proinflammatory effector cells. RA T cells had low expression of the double-strand-break repair nuclease MRE11A, leading to telomeric damage, juxtacentromeric heterochromatin unraveling, and senescence marker upregulation. Inhibition of MRE11A activity in healthy T cells induced the aging phenotype, whereas MRE11A overexpression in RA T cells reversed it. In human-synovium chimeric mice, MRE11Alow T cells were tissue-invasive and pro-arthritogenic, and MRE11A reconstitution mitigated synovitis. Our findings link premature T cell aging and tissue-invasiveness to telomere deprotection and heterochromatin unpacking, identifying MRE11A as a therapeutic target to combat immune aging and suppress dysregulated tissue inflammation.

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.

Assessing Ability for ChatGPT to Answer Total Knee Arthroplasty-Related Questions.

BACKGROUND: Artificial intelligence in the field of orthopaedics has been a topic of increasing interest and opportunity in recent years. Its applications are widespread both for physicians and patients, including use in clinical decision-making, in the operating room, and in research. In this study, we aimed to assess the quality of ChatGPT answers when asked questions related to total knee arthroplasty. METHODS: ChatGPT prompts were created by turning 15 of the American Academy of Orthopaedic Surgeons Clinical Practice Guidelines into questions. An online survey was created, which included screenshots of each prompt and answers to the 15 questions. Surgeons were asked to grade ChatGPT answers from 1 to 5 based on their characteristics: (1) relevance, (2) accuracy, (3) clarity, (4) completeness, (5) evidence-based, and (6) consistency. There were 11 Adult Joint Reconstruction fellowship-trained surgeons who completed the survey. Questions were subclassified based on the subject of the prompt: (1) risk factors, (2) implant/intraoperative, and (3) pain/functional outcomes. The average and standard deviation for all answers, as well as for each subgroup, were calculated. Inter-rater reliability (IRR) was also calculated. RESULTS: All answer characteristics were graded as being above average (ie, a score > 3). Relevance demonstrated the highest scores (4.43 ± 0.77) by surgeons surveyed, and consistency demonstrated the lowest scores (3.54 ± 1.10). ChatGPT prompts in the Risk Factors group demonstrated the best responses, while those in the Pain/Functional Outcome group demonstrated the lowest. The overall IRR was found to be 0.33 (poor reliability), with the highest IRR for relevance (0.43) and the lowest for evidence-based (0.28). CONCLUSIONS: ChatGPT can answer questions regarding well-established clinical guidelines in total knee arthroplasty with above-average accuracy but demonstrates variable reliability. This investigation is the first step in understanding large language model artificial intelligence like ChatGPT and how well they perform in the field of arthroplasty.

Improving Biocompatibility for Next Generation of Metallic Implants.

The increasing need for joint replacement surgeries, musculoskeletal repairs, and orthodontics worldwide prompts emerging technologies to evolve with healthcare's changing landscape. Metallic orthopaedic materials have a shared application history with the aerospace industry, making them only partly efficient in the biomedical domain. However, suitability of metallic materials in bone tissue replacements and regenerative therapies remains unchallenged due to their superior mechanical properties, eventhough they are not perfectly biocompatible. Therefore, exploring ways to improve biocompatibility is the most critical step toward designing the next generation of metallic biomaterials. This review discusses methods of improving biocompatibility of metals used in biomedical devices using surface modification, bulk modification, and incorporation of biologics. Our investigation spans multiple length scales, from bulk metals to the effect of microporosities, surface nanoarchitecture, and biomolecules such as DNA incorporation for enhanced biological response in metallic materials. We examine recent technologies such as 3D printing in alloy design and storing surface charge on nanoarchitecture surfaces, metal-on-metal, and ceramic-on-metal coatings to present a coherent and comprehensive understanding of the subject. Finally, we consider the advantages and challenges of metallic biomaterials and identify future directions.

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.

Clinical Assessments of Fracture Healing and Basic Science Correlates: Is There Room for Convergence?

PURPOSE OF REVIEW: The purpose of this review is to summarize the clinical and basic science methods used to assess fracture healing and propose a framework to improve the translational possibilities. RECENT FINDINGS: Mainstays of fracture healing assessment include clinical examination, various imaging modalities, and assessment of function. Pre-clinical studies have yielded insight into biomechanical progression as well as the genetic, molecular, and cellular processes of fracture healing. Efforts are emerging to identify early markers to predict impaired healing and possibly early intervention to alter these processes. Despite of the differences in clinical and preclinical research, opportunities exist to unify and improve the translational efforts between these arenas to develop and optimize our ability to assess and predict fracture healing, thereby improving the clinical care of these patients.

The Impact of Exchanging Cerclage Fixation after Extended Trochanteric Osteotomy in Revision Total Hip Arthroplasty for Periprosthetic Joint Infection.

BACKGROUND: An extended trochanteric osteotomy (ETO) is a powerful tool for femoral component revision. There is limited evidence that directly supports its use in the setting of a periprosthetic joint infection (PJI). Cerclage fixation raises the theoretical concern for persistent infection. METHODS: Our institutional database included 76 ETOs for revision hip arthroplasty between January 1, 2008 and December 31, 2019. The cohort was divided based on indication for femoral component revision: PJI versus aseptic revision. The PJI group was subdivided based on second-stage exchange versus retention of initial cerclage fixation. Operative time, estimated blood loss, complications, and rate of repeat revision surgery were evaluated. RESULTS: Forty-nine patients (64%) underwent revision for PJI and 27 patients (36%) underwent aseptic revision. There was no significant difference in operative times (P = .082), postoperative complications (P = .258), or rate of repeat revision surgery (P = .322) between groups. Of the 49 patients in the PJI group, 40 (82%) retained cerclage fixation while 9 (18%) had cerclage exchange. Cerclage exchange did not significantly impact operative time (P = .758), blood loss (P = .498), rate of repeat revision surgery (P = .302), or postoperative complications (P = .253) including infection (P = .639). CONCLUSION: An ETO remains a powerful tool for femoral component removal, even in the presence of a PJI. A multi-institutional investigation would be required to validate observed trends toward better infection control with cerclage exchange. Cerclage exchange did not appear to increase operative time, blood loss, or postoperative complication rates.

Complications, Implant Survivorships, and Functional Outcomes of Conversion Total Knee Arthroplasty With Prior Hardware.

BACKGROUND: End-stage knee osteoarthritis with retained periarticular hardware is a frequent scenario. Conversion total knee arthroplasty (TKA) leads to excellent outcomes, but poses unique challenges. The evidence supporting retention versus removal of hardware during TKA is controversial. METHODS: Patients who underwent TKA with prior hardware between January 2009 and December 2019 were identified. A total of 148 patients underwent TKA with prior hardware. The mean follow-up was 60 months (range, 24-223). Univariate and multivariable analyses were used to study correlations among factors and surgical-related complications, prosthesis failures, and functional outcomes. RESULTS: The complication rate was 28 of 148 (18.9%). The use of a quadriceps snips in addition to a medial parapatellar arthrotomy was associated with a higher complication (odds ratio: 20.7, P < .05), implant failures (odds ratio: 13.9, P < .05), and lower the Veterans Rand 12 Mental Score (VR-12 MS) (-14.8, P < .05). Hardware removal versus retention and use of single versus multiple incisions were not associated with complications or prosthesis failures. Removal of all hardware was associated with significantly higher (+7.3, P < .05) VR-12 MS compared to retention of all hardware. CONCLUSIONS: TKA with prior hardware was associated with more complications, implant failures, and lower VR-12 MS when a more constrained construct or quadriceps snip was performed. This probably reflects the level of difficulty of the procedure rather than the surgical approach used. Hardware removal or retention was not associated with complications or implant failures; however, removal rather than retention of all prior hardware is associated with increased general health outcomes. LEVEL OF EVIDENCE: IV, cohort without control.

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.

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.

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.

Relationship of Aging, Inflammation, and Skeletal Stem Cells and Their Effects on Fracture Repair.

PURPOSE OF REVIEW: This review summarizes recent investigations into the cellular and molecular effects of skeletal aging on the inflammatory response and stem cell function after fracture. RECENT FINDINGS: Proper regulation of the inflammatory phase of fracture healing is essential. Aging is associated with chronic inflammation, which inhibits bone formation and promotes bone resorption. Osteogenic differentiation and anti-senescence pathways in skeletal stem cells are impaired in geriatric fractures. As the population ages, fragility fractures will continue to represent a significant clinical problem, which will require innovative clinical solutions. Skeletal stem cells in geriatric individuals demonstrate defects in anti-senescence pathways that lead to impaired osteogenic differentiation in vitro in humans. Small molecule-based therapies can partially reverse the aging phenotype. In the future, molecular- or cell-based therapies modulating either inflammatory cells or skeletal stem cells represent potential therapeutic targets to augment contemporary fracture healing interventions in osteoporotic or aging individuals.

Macrophage Polarization and the Osteoimmunology of Periprosthetic Osteolysis.

PURPOSE OF REVIEW: Joint replacement has revolutionized the treatment of end-stage arthritis. We highlight the key role of macrophages in the innate immune system in helping to ensure that the prosthesis-host interface remains biologically robust. RECENT FINDINGS: Osteoimmunology is of great interest to researchers investigating the fundamental biological and material aspects of joint replacement. Constant communication between cells of the monocyte/macrophage/osteoclast lineage and the mesenchymal stem cell-osteoblast lineage determines whether a durable prosthesis-implant interface is obtained, or whether implant loosening occurs. Tissue and circulating monocytes/macrophages provide local surveillance of stimuli such as the presence of byproducts of wear and can quickly polarize to pro- and anti-inflammatory phenotypes to re-establish tissue homeostasis. When these mechanisms fail, periprosthetic osteolysis results in progressive bone loss and painful failure of mechanical fixation. Immune modulation of the periprosthetic microenvironment is a potential intervention to facilitate long-term durability of prosthetic interfaces.

Ageing attenuates bone healing by mesenchymal stem cells in a microribbon hydrogel with a murine long bone critical-size defect model.

BACKGROUND: Despite the high incidence of fractures and pseudoarthrosis in the aged population, a potential role for the use of mesenchymal stem cells (MSCs) in the treatment of bone defects in elderly patients has not been elucidated. Inflammation and the innate immune system, including macrophages, play crucial roles in the differentiation and activation of MSCs. We have developed lentivirus-transduced interleukin 4 (IL4) over-expressing MSCs (IL4-MSCs) to polarize macrophages to an M2 phenotype to promote bone healing in an established young murine critical size bone defect model. In the current study, we explore the potential of IL4-MSCs in aged mice. METHODS: A 2 mm femoral diaphyseal bone defect was created and fixed with an external fixation device in 15- to 17-month-old male and female BALB/c mice. Microribbon (µRB) scaffolds (Sc) with or without encapsulation of MSCs were implanted in the defect sites. Accordingly, the mice were divided into three treatment groups: Sc-only, Sc + MSCs, and Sc + IL4-MSCs. Mice were euthanized six weeks after the surgery; subsequently, MicroCT (µCT), histochemical and immunohistochemical analyses were performed. RESULTS: µCT analysis revealed that bone formation was markedly enhanced in the IL4-MSC group. Compared with the Sc-only, the amount of new bone increased in the Sc + MSCs and Sc + IL4-MSC groups. However, no bridging of bone was observed in all groups. H&E staining showed fibrous tissue within the defect in all groups. Alkaline phosphatase (ALP) staining was increased in the Sc + IL4-MSC group. The Sc + IL4-MSCs group showed a decrease in the number of M1 macrophages and an increase in the number of M2 macrophages, with a significant increase in the M2/M1 ratio. DISCUSSION: IL4 promotes macrophage polarization to an M2 phenotype, facilitating osteogenesis and vasculogenesis. The addition of IL4-MSCs in the µRB scaffold polarized macrophages to an M2 phenotype and increased bone formation; however, complete bone bridging was not observed in any specimens. These results suggest that IL4-MSCs are insufficient to heal a critical size bone defect in aged mice, as opposed to younger animals. Additional therapeutic strategies are needed in this challenging clinical scenario.

How to stop using gadolinium chelates for magnetic resonance imaging: clinical-translational experiences with ferumoxytol.

Gadolinium chelates have been used as standard contrast agents for clinical MRI for several decades. However, several investigators recently reported that rare Earth metals such as gadolinium are deposited in the brain for months or years. This is particularly concerning for children, whose developing brain is more vulnerable to exogenous toxins compared to adults. Therefore, a search is under way for alternative MR imaging biomarkers. The United States Food and Drug Administration (FDA)-approved iron supplement ferumoxytol can solve this unmet clinical need: ferumoxytol consists of iron oxide nanoparticles that can be detected with MRI and provide significant T1- and T2-signal enhancement of vessels and soft tissues. Several investigators including our research group have started to use ferumoxytol off-label as a new contrast agent for MRI. This article reviews the existing literature on the biodistribution of ferumoxytol in children and compares the diagnostic accuracy of ferumoxytol- and gadolinium-chelate-enhanced MRI. Iron oxide nanoparticles represent a promising new class of contrast agents for pediatric MRI that can be metabolized and are not deposited in the brain.

Nonoperative and Operative Bone and Cartilage Regeneration and Orthopaedic Biologics of the Hip: An Orthoregeneration Network (ON) Foundation Hip Review.

Orthoregeneration is defined as a solution for orthopaedic conditions that harnesses the benefits of biology to improve healing, reduce pain, improve function, and, optimally, provide an environment for tissue regeneration. Options include drugs, surgical intervention, scaffolds, biologics as a product of cells, and physical and electromagnetic stimuli. The goal of regenerative medicine is to enhance the healing of tissue after musculoskeletal injuries as both isolated treatment and adjunct to surgical management, using novel therapies to improve recovery and outcomes. Various orthopaedic biologics (orthobiologics) have been investigated for the treatment of pathology involving the hip, including osteonecrosis (aseptic necrosis) involving bone marrow, bone, and cartilage, and chondral injuries involving articular cartilage, synovium, and bone marrow. Promising and established treatment modalities for osteonecrosis include nonweightbearing; pharmacological treatments including low molecular-weight heparin, prostacyclin, statins, bisphosphonates, and denosumab, a receptor activator of nuclear factor-kB ligand inhibitor; extracorporeal shock wave therapy; pulsed electromagnetic fields; core decompression surgery; cellular therapies including bone marrow aspirate comprising mesenchymal stromal cells (MSCs aka mesenchymal stem cells) and bone marrow autologous concentrate, with or without expanded or cultured cells, and possible addition of bone morphogenetic protein-2, vascular endothelial growth factor, and basic fibroblast growth factor; and arterial perfusion of MSCs that may be combined with addition of carriers or scaffolds including autologous MSCs cultured with beta-tricalcium phosphate ceramics associated with a free vascularized fibula. Promising and established treatment modalities for chondral lesions include autologous platelet-rich plasma; hyaluronic acid; MSCs (in expanded or nonexpanded form) derived from bone marrow or other sources such as fat, placenta, umbilical cord blood, synovial membrane, and cartilage; microfracture or microfracture augmented with membrane containing MSCs, collagen, HA, or synthetic polymer; mosaicplasty; 1-stage autologous cartilage translation (ACT) or 2-stage ACT using 3-dimensional spheroids; and autologous cartilage grafting; chondral flap repair, or flap fixation with fibrin glue. Hip pain is catastrophic in young patients, and promising therapies offer an alternative to premature arthroplasty. This may address both physical and psychological components of pain; the goal is to avoid or postpone an artificial joint. LEVEL OF EVIDENCE: Level V, expert opinion.

Staging Bilateral Total Knee Arthroplasties Reduces Alignment Outliers.

BACKGROUND: Patients frequently present with bilateral symptomatic knee osteoarthritis and request simultaneous total knee arthroplasties (TKAs). Technical differences between simultaneous and staged TKAs could affect clinical and radiographic outcomes. We hypothesized that staged TKAs would have fewer mechanical alignment outliers than simultaneous TKAs. METHODS: We reviewed 87 simultaneous and 72 staged TKAs with at least 2 years of follow-up. Radiographic assessment was done using standing long leg and lateral radiographs of the knee. Coronal and sagittal measurements were performed by 4 blinded observers on 2 separate occasions with an intraobserver agreement of 0.95 and interobserver of 0.92. RESULTS: The first simultaneous knee had no difference in the probability of establishing the mechanical axis outside 3° of neutral (45%) compared to the first staged knee (54%, P = .337). However, the second simultaneous knee (49%) was more likely to establish the axis outside mechanical neutral compared to the second staged knee (28%; odds ratio 2.54, confidence interval 1.31-4.94, P = .006). There was an increased risk of deep venous thrombosis with staged TKA (odds ratio 2.96, confidence interval 1.28-6.84, P = .011), but other perioperative complication rates were not significantly different. There were no clinically significant differences in range of motion or Knee Society Score. CONCLUSION: There is a significantly increased risk of establishing the second knee outside mechanical neutral during a simultaneous TKA compared to staged bilateral TKAs, possibly related to a number of surgeon-related and system-related factors. The impact on clinical outcomes and radiographic loosening may become significant in long-term follow-up.

The 2021 Association Research Circulation Osseous Classification for Early-Stage Osteonecrosis of the Femoral Head to Computed Tomography-Based Study.

BACKGROUND: The Association Research Circulation Osseous developed a novel classification for early-stage (precollapse) osteonecrosis of the femoral head (ONFH). We hypothesized that the novel classification is more reliable and valid when compared to previous 3 classifications: Steinberg, modified Kerboul, and Japanese Investigation Committee classifications. METHODS: In the novel classification, necrotic lesions were classified into 3 types: type 1 is a small lesion, where the lateral necrotic margin is medial to the femoral head apex; type 2 is a medium-sized lesion, with the lateral necrotic margin being between the femoral head apex and the lateral acetabular edge; and type 3 is a large lesion, which extends outside the lateral acetabular edge. In a derivation cohort of 40 early-stage osteonecrotic hips based on computed tomography imaging, reliabilities were evaluated using kappa coefficients, and validities to predict future femoral head collapse by chi-squared tests and receiver operating characteristic curve analyses. The predictability for future collapse was also evaluated in a validation cohort of 104 early-stage ONFH. RESULTS: In the derivation cohort, interobserver reliability (k = 0.545) and intraobserver agreement (63%-100%) of the novel method were higher than the other 3 classifications. The novel classification system was best able to predict future collapse (P < .05) and had the best discrimination between non-progressors and progressors in both the derivation cohort (area under the curve = 0.692 [0.522-0.863], P < .05) and the validation cohort (area under the curve = 0.742 [0.644-0.841], P = 2.46 × 10-5). CONCLUSION: This novel classification is a highly reliable and valid method of those examined. Association Research Circulation Osseous recommends using this method as a unified classification for early-stage ONFH. LEVEL OF EVIDENCE: Level III, diagnostic study.

Efficacy of Periarticular Multimodal Analgesic Injection Containing High-Dose Ketorolac versus Triamcinolone in Early Postoperative Total Knee Arthroplasty: A Randomized Controlled Trial.

INTRODUCTION: Periarticular multimodal analgesic injection associates with less postoperative (post-op) pain after total knee arthroplasty (TKA) with less opioid consumption. The combination of additives and dosage are various and controversial. Evidence of ketorolac compared to triamcinolone as an additive is limited in terms of efficacy and safety. MATERIALS AND METHODS: Fifty-six patients with unilateral TKA were randomized to receive either 60mg ketorolac or 80mg triamcinolone acetonide as cocktail additives in periarticular injection. Significant threshold was considered if the adjusted mean difference of morphine consumption was greater than 3mg at any timepoint. The primary outcomes were morphine consumptions at immediate post-op, 24 hour (h), 48h, and 72h post-op. Pain visual analogue scale (VAS), knee range of motion, straight leg raising ability, and adverse events were secondary outcomes. RESULTS: Adjusted mean differences (ketorolac-triamcinolone) in morphine consumption were -0.4, 2.5, 2.6, and 2.3mg at given timepoints without significance. No difference observed in pain VAS at rest and during motion, post-op knee extension, and straight leg raising ability. However, post-op knee flexion was significantly higher in triamcinolone group at any timepoints (mean differences 10.3, 10.6, and 9.7, respectively, p<0.05). CONCLUSIONS: Periarticular analgesic injection containing 60mg ketorolac provided similar analgesic efficacy and early functional recovery compared with 80mg triamcinolone acetonide. However, triamcinolone may benefit over ketorolac in early post-op knee flexion.