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Background: Correction of a fixed flexion deformity is an important goal when performing total knee arthroplasty. The purpose of this study was to assess the accuracy of clinical assessment compared with imageless computer navigation in determining the degree of fixed flexion.Methods: We performed navigation anatomy registration using 14 cadaver knees.The knees were held in various degrees of flexion with 2 crossed pins. The degree of flexion was first recorded on the computer and then on lateral radiographs. The cadaver knees were draped as they would be for a total knee arthroplasty, and 9 examiners were asked to clinically assess by visual observation the amount of fixed flexion.Three examiners repeated the process 1 week later.Results: The mean error from the radiographs in the navigation group was 2.18 degrees (95% confidence interval [CI] 1.23 degrees -3.01 degrees) compared with 5.57 degrees (95% CI 4.86 degrees -6.29 degrees) in the observer group. The navigation was more consistent, with a range of error of -5 degrees to +5.5 degrees compared with -18.5 degrees to +17.5 degrees in the observer group. The observers tended to underestimate the amount of knee flexion (median error -4 degrees), whereas the navigation group was more evenly distributed (median error 0). The highest concordance coefficient was found between navigation and radiography (0.96). The concordance coefficient was 0.88 for the 3 surgeons who repeated the measurements 1 week later (mean error 3.5 degrees , range 15 degrees ).Conclusion: The use of computer navigation appears to be a more accurate method for assessing the degree of knee flexion, with a reduced range of error compared with clinical assessment. The use of computer-assisted surgery may therefore provide surgeons with the information required to more consistently restore full extension during total knee arthroplasty. [ABSTRACT FROM AUTHOR]

Objective: To identify whether patients in lower socioeconomic groups had worse pain and functional levels prior to total knee arthroplasty and then establish whether these patients had poorer post-operative outcomes following total knee arthroplasty.Method: Data was obtained from a prospective observational study of 974 patients undergoing primary total knee arthroplasty for osteoarthritis. The study was undertaken in 13 centers in 4 countries. Pre-operative data was collected and patients were followed for 2 years post-operatively. Pre-operative details of the patients' demographics; socioeconomic status (SES) (education and income); height; weight and co-morbid conditions were obtained. The WOMAC scores were obtained preoperatively and during follow-up.Results: Using multivariate linear regression analysis, patients with a lower income had a significantly worse pre-operative WOMAC Pain (P = 0.021) and function score (P = 0.039) than those with higher incomes. However, income did not have a significant impact on outcome at final follow-up after adjusting for other significant covariates. Level of education did not correlate with pre-operative scores or with outcome at any time during follow-up.Conclusion: Across all four countries, patients with lower incomes appeared to have a greater need for total knee arthroplasty. However, level of income and educational status did not appear to affect the final outcome following total knee arthroplasty. Patients with lower incomes appeared able to compensate for their worse pre-operative score and obtain similar outcomes post-operatively. These findings are in contrast to studies on other medical conditions and surgical interventions, in which a lower SES has been found to have a negative impact on patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Many treatments for osteonecrosis of the femoral head, including the use of a free vascularized fibular graft, have been advocated in an attempt to delay the need for hip arthroplasty. The purpose of this study was to document the clinical and radiographic results of total hip arthroplasty performed following failure of a free vascularized fibular grafting procedure.Methods: Twenty total hip arthroplasties in eighteen patients who had previously undergone a free vascularized fibular grafting procedure for the treatment of osteonecrosis were retrospectively reviewed. A straight-stem femoral component was used in twelve hips, a tapered femoral component with removal of residual fibular graft was used in five hips, and a tapered stem without graft removal was used in three hips. The twelve hips with a straight-stem femoral component and previous vascularized fibular grafting were compared with thirty-six osteonecrotic hips in thirty other patients who had undergone total hip arthroplasty but had not had previous free vascularized fibular grafting. The radiographic outcomes with respect to initial femoral component alignment and subsequent migration and the clinical outcomes were compared.Results: Analysis of the immediate postoperative radiographs demonstrated significantly improved alignment of the femoral component when a high-speed burr had been used to remove residual fibular graft (p = 0.001), although doing so did significantly increase both the intraoperative blood loss (p = 0.017) and the operative time (p = 0.0002). There was no significant difference in the amount of migration of either the acetabular or the femoral component between the control and study groups at the time of the most recent follow-up. When comparing patients with or without a previous free vascularized fibular graft, the mean postoperative scores at three years were significantly worse in patients who had undergone a previous free vascularized fibular graft (p = 0.03). One revision occurred in the study group at seventy-two months due to acetabular wear, and one revision occurred in the control group at 108 months due to aseptic loosening.Conclusions: This study raises concern that the outcome of total hip arthroplasty in patients who previously underwent a free vascularized fibular graft for the treatment of osteonecrosis of the femoral head may be worse than that in patients without previous free vascularized fibular grafting. The intraoperative use of a high-speed burr can improve the alignment of the femoral component by removing more of the residual graft. However, this technique does increase intraoperative blood loss and operative time.Level Of Evidence: Therapeutic Level IV. See Instructions to Authors on jbjs.org for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Objective: To establish the accuracy of information available on the Internet regarding hip resurfacing.Method: The top 100 sites found in response to the query 'hip resurfacing' using Google were assessed for quality using the DISCERN instrument and the JAMA benchmarks.Results: Of the top 100 sites found, only 30 were relevant, available and unique. Of these only six (20%) scored highly for overall quality; however, ten (33%) sites achieved the lowest possible score. Risks and complications were not commonly presented nor were results of surgery. In one case, results presented were grossly misleading.Conclusions: The use of the Internet to directly market specific products to the public raises the concern that patients are not always fully informed. The quality of health information on the Internet relating to hip resurfacing is of frequently poor and variable quality. Eighty per cent of the sites that we assessed had serious shortcomings. [ABSTRACT FROM AUTHOR]

Cellular plasticity is a hallmark of pancreatic ductal adenocarcinoma (PDAC) starting from the conversion of normal cells into precancerous lesions, to the progression of carcinoma subtypes associated with aggressiveness and therapeutic response. We discovered that normal acinar cell differentiation, maintained by the transcription factor PDX1, suppresses a broad gastric cell identity that is maintained in metaplasia, neoplasia, and the classical subtype of PDAC in a mouse and human. We identified the receptor tyrosine kinase ROR2 as marker of a gastric metaplasia-like identity in pancreas neoplasms. Ablation of Ror2 in a mouse model of pancreatic tumorigenesis promoted a switch to a gastric pit cell identity that largely persisted through progression to the classical subtype of PDAC. In both human and mouse pancreatic cancer, ROR2 activity continued to antagonize the gastric pit cell identity, strongly promoting an epithelial to mesenchymal transition, conferring resistance to KRAS inhibition, and vulnerability to AKT inhibition. Significance: We discovered the receptor tyrosine kinase ROR2 as an important regulator of cellular identity in pancreatic precancerous lesions and pancreatic cancer. ROR2 drives an aggressive PDAC phenotype and confers resistance to KRAS inhibitors, suggesting that targeting ROR2 will enhance sensitivity to this new generation of targeted therapies. See related commentary by Marasco and Misale, p. 2018., (©2024 The Authors; Published by the American Association for Cancer Research.)

Objective: Synovitis is a widely accepted sign of osteoarthritis (OA), characterised by tissue hyperplasia, where increased infiltration of immune cells and proliferation of resident fibroblasts adopt a pro-inflammatory phenotype, and increased the production of pro-inflammatory mediators that are capable of sensitising and activating sensory nociceptors, which innervate the joint tissues. As such, it is important to understand the cellular composition of synovium and their involvement in pain sensitisation to better inform the development of effective analgesics., Methods: Studies investigating pain sensitisation in OA with a focus on immune cells and fibroblasts were identified using PubMed, Web of Science and SCOPUS., Results: In this review, we comprehensively assess the evidence that cellular crosstalk between resident immune cells or synovial fibroblasts with joint nociceptors in inflamed OA synovium contributes to peripheral pain sensitisation. Moreover, we explore whether the elucidation of common mechanisms identified in similar joint conditions may inform the development of more effective analgesics specifically targeting OA joint pain., Conclusion: The concept of local environment and cellular crosstalk within the inflammatory synovium as a driver of nociceptive joint pain presents a compelling opportunity for future research and therapeutic advancements., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Hyaluronic acid (HA) based nanogels showed effective intracellular delivery efficacy for anti-cancer and anti-inflammatory drugs, characterized by their ability targeting relevant cell receptors. In the present study, we demonstrate the ability of hyaluronic acid-polyethyleneimine (HA-PEI) nanogels as a promising dual-functional interfacial active for intra-articular injection to intervene arthritis. Nanomechanical measurements on both model substrates and human cartilage samples confirm that the HA-PEI nanogels can significantly improve interfacial lubrication, in comparison to HA molecules, or silica-based nanoparticles. We show that the Coefficient of Friction significantly decreases with a decreasing nanogel size. The exceptional lubricating performance, coupled with the proven drug delivery capability, evidences the great potential of nanoscopic hydrogels for early-stage arthritis treatment. The flexibility in choosing the chemical nature, molecular architecture, and structural characteristics of nanogels makes it possible to modulate both drug delivery kinetics and interfacial lubrication, thus representing an innovative approach to treat degenerative joint diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: There is growing interest in the use of robotic TKA to improve accuracy of component positioning in Total Knee Arthroplasty (TKA). The aim of this study was to investigate the accuracy of implant component position using the ROSA® knee system with specific reference to Joint Line Height, Patella Height and Posterior Condylar Offset (PCO)., Methods: This was a retrospective review of a prospectively-maintained database of the initial 100 consecutive TKAs performed by a high volume surgeon using the ROSA® knee system. Both the image-based and imageless workflow were used and two prosthesis types were implanted. To determine the accuracy of component positioning, the immediate post-operative radiograph was reviewed and compared with the immediate pre-operative radiograph with regards to Joint Line Height, Patella Height and Posterior Condylar Offset., Results: 100 consecutive patients undergoing TKA using the ROSA system were included; mean age 70 years (range 49-95 years). Mean change in joint line height was 0.2 mm, patella height (Insall-Salvati ratio) 0.01 and posterior condylar offset 0.02 mm; there was no statistically significant difference between the pre and post-operative values. No difference was demonstrated between image-based or imageless workflows, or between implant design (Persona versus Vanguard) regarding joint line height, patella height and PCO., Conclusion: This study validates the use of the ROSA® knee system in accurately restoring Joint Line Height, Patella Height and Posterior Condylar Offset in TKA surgery. No significant differences were found between imageless and image-based groups, or between implant designs (Persona versus Vanguard)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Understanding how patients perceive and prioritise various aspects of recovery following total knee replacement, including pain, function and return to activity, will help clinicians in pre-operative consultations by ensuring they effectively address patient concerns and managing their expectations., Aims: The aim of this study is to identify aspects of recovery that are important to people after a total knee replacement., Methods: Studies were identified from Medline, Embase, PsycInfo, Cochrane Library and Web of Science. This mixed methods review included all original study types (quantitative, qualitative, discrete choice experiments and mixed methods design). Reviews and non-peer-reviewed publications were excluded. Studies with participants (age ≥ 18 years) who had a primary TKR for osteoarthritis were included. Studies of people with unicompartmental knee, patella-femoral or revision knee replacement were excluded. Recovery attributes were extracted from individual papers and grouped into recovery themes., Results: A total of 23 studies with 8404 participants and 18 recovery themes were developed. The most frequently identified overarching theme was pain, followed by activities of daily living, mobility (walking), recreational activities, specific functional movements of the knee, use of walking aids, sexual activity and range of motion of the knee. Medical complications were an infrequently reported theme, however, was deemed to be high importance., Conclusions: Reducing pain, returning of activities and daily living and mobility are the three most frequently reported recovery domains for people after TKR. Clinicians should be aware of recovery themes, to ensure they are explored sufficiently when consenting for a TKR. Future research should aim to determine the relative importance of these attributes compared to each other. Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021253699., (© 2023. The Author(s).)

Total hip and knee arthroplasty (THA, TKA) are largely successful procedures; however, both have variable outcomes, resulting in some patients being dissatisfied with the outcome. Surgeons are turning to technologies such as robotic-assisted surgery in an attempt to improve outcomes. Robust studies are needed to find out if these innovations are really benefitting patients. The Robotic Arthroplasty Clinical and Cost Effectiveness Randomised Controlled Trials (RACER) trials are multicentre, patient-blinded randomized controlled trials. The patients have primary osteoarthritis of the hip or knee. The operation is Mako-assisted THA or TKA and the control groups have operations using conventional instruments. The primary clinical outcome is the Forgotten Joint Score at 12 months, and there is a built-in analysis of cost-effectiveness. Secondary outcomes include early pain, the alignment of the components, and medium- to long-term outcomes. This annotation outlines the need to assess these technologies and discusses the design and challenges when conducting such trials, including surgical workflows, isolating the effect of the operation, blinding, and assessing the learning curve. Finally, the future of robotic surgery is discussed, including the need to contemporaneously introduce and evaluate such technologies., Competing Interests: C. Khatri receives a salary as a Clinical Research Fellow as a part of the RACER Knee Trial. A. Metcalfe reports no conflicts of interest relevant to the current study; he is Co-Chief Investigator for the RACER-Knee trial, and an Investigator on three National Institute for Health and Care Research (NIHR)-funded trials (Chief Investigator for START:REACTS and RACER-Knee and Co-Investigator for RACER-Hip). P. Wall is Co-Chief Investigator for RACER-Hip trial, and a Chief Investigator for a Medacta-funded study examining the use of custom guides for pelvic periacetabular osteotomy surgery. M. Underwood reports no conflicts of interest relevant to the current study; he is a Co-Investigator for the RACER trial, and a Co-Investigator on three NIHR-funded trials (START:REACTS, RACER-Knee and RACER-Hip). F. S. Haddad is a Chief Investigator for three ongoing randomized controlled studies at University College London Hospitals on robotic hip and knee surgery, and is a Co-Investigator for the RACER-Knee and RACER-Hip trials. F. S. Haddad is also Editor-in-Chief of The Bone & Joint Journal, and reports research grants from Stryker, Smith & Nephew, Corin, International Olympic Committee, and NIHR, royalties or licenses from Smith & Nephew, Stryker, Corin, and MatOrtho, consulting fees from Stryker, speaker payments from Stryker, Smith & Nephew, Zimmer, and AO Recon, and travel expenses from Stryker, Smith & Nephew, AO Recon, and The Bone & Joitn Journal. F. S. Haddad is also a Trustee of the British Orthopaedic Association and a member of the Bostaa Executive Committee. E. T. Davis is Co-Chief Investigator for RACER-Knee and RACER-Hip trials. E. T. Davis also reports research funding, consulting fees, speaker payments, payment for expert testimony, and travel expenses from Smith & Nephew, and speaker payments and research funding from Stryker, all of which are unrelated to this study. For the RACER trials, Stryker, a medical device company, funds all excess treatment costs associated with the study intervention and some imaging costs. For all these studies, the full independence of the study team is protected by legal agreements, and they have no bearing on the presented manuscript., (© 2024 The British Editorial Society of Bone & Joint Surgery.)

There is increasing adoption of robotic surgical technology in Total Knee Arthroplasty. The ROSA® knee system can be used in either image-based mode (using pre-operative calibrated radiographs) or imageless modes (using intra-operative bony registration). The Mako knee system is an image-based system (using a pre-operative CT scan). This study aimed to compare surgical accuracy between the ROSA and Mako systems with specific reference to joint line height, patella height, posterior condylar offset and tibial slope. This was a retrospective review of a prospectively collected data of the initial 50 consecutive ROSA TKAs and the initial 50 consecutive Mako TKAs performed by two high-volume surgeons. To determine the accuracy of component positioning, the immediate post-operative radiograph was reviewed and compared with the immediate pre-operative radiograph with regards to joint line height (JLH), patella height (PH), tibial slope (TS) and posterior condylar offset (PCO). Mean difference between pre- and post-operative radiographs using the ROSA knee system of joint line height was 0.47 mm (SD 0.95) posterior condylar offset 0.16 mm (SD 0.76), tibial slope 0.9 degrees (SD 1.6) and patella height 0.01 (SD 0.05). Mean difference using the MAKO knee system of joint line height was 0.26 (SD 1.08), posterior condylar offset -0.26 mm (SD 0.78), tibial slope 1.8 degrees and patella height 0.03. No significant difference was demonstrated between the accuracy of component positioning of the ROSA or MAKO knee systems. Our study is the first study to compare the accuracy of the ROSA and MAKO knee systems in total knee arthroplasty. Both systems are highly accurate in restoring native posterior condylar offset, joint line height, tibial slope and patella height in TKA with no significant difference demonstrated between the two groups., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Introduction: The number of robotic-assisted hip replacement procedures has expanded globally with the intended aim of improving outcomes. Intraoperative robotic-arm systems add additional costs to total hip replacement (THR) surgery but may improve surgical precision and could contribute to diminished pain and improved function. Additionally, these systems may reduce the need for expensive revision surgery. Surgery with conventional instruments may be just as successful, quick and affordable. There is timely demand for a robust evaluation of this technology., Methods and Analysis: The Robotic Arthroplasty Clinical and cost Effectiveness Randomised controlled trial for Hips (RACER-Hip) is a multicentre (minimum of six UK sites), participant-assessor blinded, randomised controlled trial. 378 participants with hip osteoarthritis requiring THR will be randomised (1:1) to receive robotic-assisted THR, or THR using conventional surgical instruments. The primary outcome is the Forgotten Joint Score at 12 months post-randomisation; a patient-reported outcome measure assessing participants' awareness of their joint when undertaking daily activities. Secondary outcomes will be collected post-operatively (pain, blood loss and opioid usage) and at 3, 6, 12, 24 months, then 5 and 10 years postrandomisation (including function, pain, health-related quality of life, reoperations and satisfaction). Allocation concealment will be accomplished using a computer-based randomisation procedure on the day of surgery. Blinding methods include the use of sham incisions for marker clusters and blinded operation notes. The primary analysis will adhere to the intention-to-treat principle. Results will adhere to Consolidated Standards of Reporting Trials statements., Ethics and Dissemination: The trial was approved by an ethics committee (Solihull Research Ethics Committee, 30 June 2021, IRAS: 295831). Participants will provide informed consent before agreeing to participate. Results will be disseminated using peer-reviewed journal publications, presentations at international conferences and through the use of social media. We will develop plans to disseminate to patients and public with our patient partners., Trial Registration Number: ISRCTN13374625., Competing Interests: Competing interests: Stryker is providing funding for consumables, surgical instruments, preoperative CT costs,15 min of theatre time and the provision of robotic systems at two of the recruitment sites, according to contractual arrangements which align fully with the National Institute for Health Research (NIHR) contracts. Appropriate contracts are in place to ensure the independence of the trial team with regard to study design, data collection, management, analysis and interpretation in-line with NIHR reporting standards. MU has been a chief investigator and is current, or past, coinvestigator on multiple previous and current research grants from the UK NIHR, and is a coinvestigator on grants funded by the Australian NHMRC and Norwegian MRC. He was an NIHR Senior Investigator until March 2021. He is a director and shareholder of Clinvivo that provides electronic data collection for health services research. He is part of an academic partnership with Serco, funded by the European Social Fund, related to return to work initiatives. He receives some salary support from University Hospitals Coventry and Warwickshire. He is a coinvestigator on two current and one completed NIHR-funded studies that have, or have had, additional support from Stryker. DRE, HP, JB and JG are supported from NIHR Research Capability Funding via University Hospitals Coventry and Warwickshire. JB and TS have been and is currently coapplicant on multiple previous and current research grants from the UK NIHR. JB has had travel expenses reimbursed by societies/organisations for invited contributions. TS has acted as Associate Editor for clinical journals and as a Committee member on the UK NICE Technology Committee. FH has held multiple research study grants with Stryker. In addition, he has held research grants from Smith & Nephew, Corin, IOC, NIHR. FH has royalties with Smith & Nephew, Stryker, Corin and MatOrtho. FH has received consulting fees from Stryker. FH has received support for attending meetings and/or travel from Stryker, Smith & Nephew, AO Recon, Bone and Joint Journal. FSH is a member of the Bone and Joint Journal Editorial Board, a trustee of the British Orthopaedic Association and a member of the BOSTAA Executive Committee. All other authors declared no additional competing interests., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: The aim of this study was to identify the optimal lip position for total hip arthroplasties (THAs) using a lipped liner. There is a lack of consensus on the optimal position, with substantial variability in surgeon practice., Methods: A model of a THA was developed using a 20° lipped liner. Kinematic analyses included a physiological range of motion (ROM) analysis and a provocative dislocation manoeuvre analysis. ROM prior to impingement was calculated and, in impingement scenarios, the travel distance prior to dislocation was assessed. The combinations analyzed included nine cup positions (inclination 30-40-50°, anteversion 5-15-25°), three stem positions (anteversion 0-15-30°), and five lip orientations (right hip 7 to 11 o'clock)., Results: The position of the lip changes the ROM prior to impingement, with certain combinations leading to impingement within the physiological ROM. Inferior lip positions (7 to 8 o'clock) performed best with cup inclinations of 30° and 40°. Superior lip positions performed best with cup inclination of 50°. When impingement occurs in the plane of the lip, the lip increases the travel distance prior to dislocation. Inferior lip positions led to the largest increase in jump distance in a posterior dislocation provocation manoeuvre., Conclusion: The lip orientation that provides optimal physiological ROM depends on the orientation of the cup and stem. For a THA with stem anteversion 15°, cup inclination 40°, and cup anteversion 15°, the optimal lip position was posterior-inferior (8 o'clock). Maximizing jump distance prior to dislocation while preventing impingement in the opposite direction is possible with appropriate lip positioning., Competing Interests: A. Navacchia is an employee of Smith+Nephew., (© 2023 Author(s) et al.)

Background: Osteonecrosis of the femoral head (ONFH) is a disabling disease that can ultimately progress to collapse of the femoral head, often resulting in THA. Core decompression of the femoral head combined with cell therapies have shown beneficial effects in previous clinical studies in patients with early-stage (Association Research Circulation Osseous [ARCO] Stage I and II) ONFH. However, high-quality evidence confirming the efficacy of this treatment modality is still lacking., Questions/purposes: (1) Is core decompression combined with autologous osteoblastic cell transplantation superior to core decompression with placebo implantation in relieving disease-associated pain and preventing radiologic ONFH progression in patients with nontraumatic early-stage ONFH? (2) What adverse events occurred in the treatment and control groups?, Methods: This study was a Phase III, multicenter, randomized, double-blind, controlled study conducted from 2011 to 2019 (ClinicalTrails.gov registry number: NCT01529008). Adult patients with ARCO Stage I and II ONFH were randomized (1:1) to receive either core decompression with osteoblastic cell transplantation (5 mL with 20 x 10 6 cells/mL in the study group) or core decompression with placebo (5 mL of solution without cells in the control group) implantation. Thirty percent (68 of 230) of the screened patients were eligible for inclusion in the study; of these, 94% (64 of 68) underwent a bone marrow harvest or sham procedure (extended safety set) and 79% (54 of 68) were treated (study group: 25 patients; control group: 29). Forty-nine patients were included in the efficacy analyses. Similar proportions of patients in each group completed the study at 24 months of follow-up (study group: 44% [11 of 25]; control: 41% [12 of 29]). The study and control groups were comparable in important ways; for example, in the study and control groups, most patients were men (79% [27 of 34] and 87% [26 of 30], respectively) and had ARCO Stage II ONFH (76% [19 of 25] and 83% [24 of 29], respectively); the mean age was 46 and 45 years in the study and control groups, respectively. The follow-up period was 24 months post-treatment. The primary efficacy endpoint was the composite treatment response at 24 months, comprising the clinical response (clinically important improvement in pain from baseline using the WOMAC VA3.1 pain subscale, defined as 10 mm on a 100-mm scale) and radiologic response (the absence of progression to fracture stage [≥ ARCO Stage III], as assessed by conventional radiography and MRI of the hips). Secondary efficacy endpoints included the percentages of patients achieving a composite treatment response, clinical response, and radiologic response at 12 months, and the percentage of patients undergoing THA at 24 months. We maintained a continuous reporting system for adverse events and serious adverse events related to the study treatment, bone marrow aspiration and sham procedure, or other study procedures throughout the study. A planned, unblinded interim analysis of efficacy and adverse events was completed at 12 months. The study was discontinued because our data safety monitoring board recommended terminating the study for futility based on preselected futility stopping rules: conditional power below 0.20 and p = 0.01 to detect an effect size of 10 mm on the 100-mm WOMAC VA3.1 pain subscale (improvement in pain) and the absence of progression to fracture (≥ ARCO Stage III) observed on radiologic assessment, reflecting the unlikelihood that statistically beneficial results would be reached at 24 months after the treatment., Results: There was no difference between the study and control groups in the proportion of patients who achieved a composite treatment response at 24 months (61% [14 of 23] versus 69% [18 of 26]; p = 0.54). There was no difference in the proportion of patients with a treatment response at 12 months between the study and control groups (14 of 21 versus 15 of 23; p = 0.92), clinical response (17 of 21 versus 16 of 23; p = 0.38), and radiologic response (16 of 21 versus 18 of 23; p = 0.87). With the numbers available, at 24 months, there was no difference in the proportion of patients who underwent THA between the study and control groups (24% [six of 25] versus 14% [four of 29]). There were no serious adverse events related to the study treatment, and only one serious adverse event (procedural pain in the study group) was related to bone marrow aspiration. Nonserious adverse events related to the treatment were rare in the study and control groups (4% [one of 25] versus 14% [four of 29]). Nonserious adverse events related to bone marrow or sham aspiration were reported by 15% (five of 34) of patients in the study group and 7% (two of 30) of patients in the control group., Conclusion: Our study did not show any advantage of autologous osteoblastic cells to improve the results of core decompression in early-stage (precollapse) ONFH. Adverse events related to treatment were rare and generally mild in both groups, although there might have been a potential risk associated with cell expansion. Based on our findings, we do not recommend the combination of osteoblastic cells and core decompression in patients with early-stage ONFH. Further, well-designed studies should be conducted to explore whether other treatment modalities involving a biological approach could improve the overall results of core decompression., Level of Evidence: Level II, therapeutic study., Competing Interests: All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2023 by the Association of Bone and Joint Surgeons.)

Introduction: Robotic-assisted knee replacement systems have been introduced to healthcare services worldwide in an effort to improve clinical outcomes for people, although high-quality evidence that they are clinically, or cost-effective remains sparse. Robotic-arm systems may improve surgical accuracy and could contribute to reduced pain, improved function and lower overall cost of total knee replacement (TKR) surgery. However, TKR with conventional instruments may be just as effective and may be quicker and cheaper. There is a need for a robust evaluation of this technology, including cost-effectiveness analyses using both within-trial and modelling approaches. This trial will compare robotic-assisted against conventional TKR to provide high-quality evidence on whether robotic-assisted knee replacement is beneficial to patients and cost-effective for healthcare systems., Methods and Analysis: The Robotic Arthroplasty Clinical and cost Effectiveness Randomised controlled trial-Knee is a multicentre, participant-assessor blinded, randomised controlled trial to evaluate the clinical and cost-effectiveness of robotic-assisted TKR compared with TKR using conventional instruments. A total of 332 participants will be randomised (1:1) to provide 90% power for a 12-point difference in the primary outcome measure; the Forgotten Joint Score at 12 months postrandomisation. Allocation concealment will be achieved using computer-based randomisation performed on the day of surgery and methods for blinding will include sham incisions for marker clusters and blinded operation notes. The primary analysis will adhere to the intention-to-treat principle. Results will be reported in line with the Consolidated Standards of Reporting Trials statement. A parallel study will collect data on the learning effects associated with robotic-arm systems., Ethics and Dissemination: The trial has been approved by an ethics committee for patient participation (East Midlands-Nottingham 2 Research Ethics Committee, 29 July 2020. NRES number: 20/EM/0159). All results from the study will be disseminated using peer-reviewed publications, presentations at international conferences, lay summaries and social media as appropriate., Trial Registration Number: ISRCTN27624068., Competing Interests: Competing interests: Stryker is providing funding for consumables, preoperative CT costs and 10 min of theatre time, according to contractual arrangements. They also fund some postoperative CT costs in the learning effects study. Appropriate contracts are in place to ensure the independence of the trial team with regard to study design, data collection, management, analysis and interpretation in line with NIHR reporting standards. Multiple investigators are investigators on two other NIHR-funded studies receiving additional support for treatment costs from Stryker, START:REACTS (16/61/18) (AM, HP, CEH, JM and MU) and RACER-Hip (NIHR131407) (AM, ETD, HP, SR, CEH, DRE, JM, FSH, JAS and MU). The full independence of the investigators of these related studies are protected by legal agreements, similar to this study. FSH receives funding from Stryker to run clinical studies. Multiple authors report other unrelated research grants from NIHR during the conduct of the study. DRE, HP and JG are supported from NIHR Research Capability Funding via University Hospitals Coventry and Warwickshire. MU is chief investigator or coinvestigator on multiple previous and current research grants from the UK National Institute for Health Research, Arthritis Research UK and is a coinvestigator on grants funded by the Australian NHMRC and Norwegian MRC. He was an NIHR Senior Investigator until March 2021. He has received travel expenses for speaking at conferences from the professional organisations hosting the conferences. He is a director and shareholder of Clinvivo that provides electronic data collection for health services research. He is part of an academic partnership with Serco Ltd, funded by the European Social Fund, related to return to work initiatives. Until March 2020 he was an editor of the NIHR journal series, and a member of the NIHR Journal Editors Group, for which he received a fee., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Osteoarthritis (OA), a multifaceted condition, poses a significant challenge for the successful clinical development of therapeutics due to heterogeneity. However, classifying molecular endotypes of OA pathogenesis could provide invaluable phenotype-directed routes for stratifying subgroups of patients for targeted therapeutics, leading to greater chances of success in trials. This study establishes endotypes in OA soft joint tissue driven by obesity in both load-bearing and non-load bearing joints., Methods: Hand, hip, knee and foot joint synovial tissue was obtained from OA patients (n = 32) classified as obese (BMI > 30) or normal weight (BMI 18.5-24.9). Isolated fibroblasts (OA SF) were assayed by Olink proteomic panel, seahorse metabolic flux assay, Illumina's NextSeq 500 bulk and Chromium 10X single cell RNA-sequencing, validated by Luminex and immunofluorescence., Results: Targeted proteomic, metabolic and transcriptomic analysis found the inflammatory landscape of OA SFs are independently impacted by obesity, joint loading and anatomical site with significant heterogeneity between obese and normal weight patients, confirmed by bulk RNAseq. Further investigation by single cell RNAseq identified four functional molecular endotypes including obesity specific subsets defined by an inflammatory endotype related to immune cell regulation, fibroblast activation and inflammatory signaling, with up-regulated CXCL12, CFD and CHI3L1 expression. Luminex confirmed elevated chitase3-like-1(229.5 vs. 49.5 ng/ml, p < .05) and inhibin (20.6 vs. 63.8 pg/ml, p < .05) in obese and normal weight OA SFs, respectively. Lastly, we find SF subsets in obese patients spatially localise in sublining and lining layers of OA synovium and can be distinguished by differential expression of the transcriptional regulators MYC and FOS., Conclusion: These findings demonstrate the significance of obesity in changing the inflammatory landscape of synovial fibroblasts in both load bearing and non-load bearing joints. Describing multiple heterogeneous OA SF populations characterised by specific molecular endotypes, which drive heterogeneity in OA disease pathogenesis. These molecular endotypes may provide a route for the stratification of patients in clinical trials, providing a rational for the therapeutic targeting of specific SF subsets in specific patient populations with arthritic conditions., (© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Cells respond to environmental stress by regulating gene expression at the level of both transcription and translation. The ∼50 modified ribonucleotides of the human epitranscriptome contribute to the latter, with mounting evidence that dynamic regulation of transfer RNA (tRNA) wobble modifications leads to selective translation of stress response proteins from codon-biased genes. Here we show that the response of human hepatocellular carcinoma cells to arsenite exposure is regulated by the availability of queuine, a micronutrient and essential precursor to the wobble modification queuosine (Q) on tRNAs reading GUN codons. Among oxidizing and alkylating agents at equitoxic concentrations, arsenite exposure caused an oxidant-specific increase in Q that correlated with up-regulation of proteins from codon-biased genes involved in energy metabolism. Limiting queuine increased arsenite-induced cell death, altered translation, increased reactive oxygen species levels, and caused mitochondrial dysfunction. In addition to demonstrating an epitranscriptomic facet of arsenite toxicity and response, our results highlight the links between environmental exposures, stress tolerance, RNA modifications, and micronutrients.

Cigarette consumption negatively impacts bone quality and is a risk-factor for the development of multiple bone associated disorders, due to the highly vascularised structure of bone being exposed to systemic factors. However, the impact on bone to electronic cigarette (e-cigarette) use, which contains high doses of nicotine and other compounds including flavouring chemicals, metal particulates and carbonyls, is poorly understood. Here, we present the first evidence demonstrating the impact of e-cigarette vapour condensate (replicating changes in e-cigarette liquid chemical structure that occur upon device usage), on human primary osteoblast viability and function. 24 h exposure of osteoblasts to e-cigarette vapour condensate, generated from either second or third generation devices, significantly reduced osteoblast viability in a dose dependent manner, with condensate generated from the more powerful third generation device having greater toxicity. This effect was mediated in-part by nicotine, since exposure to nicotine-free condensate of an equal concentration had a less toxic effect. The detrimental effect of e-cigarette vapour condensate on osteoblast viability was rescued by co-treatment with the antioxidant N-Acetyl-L-cysteine (NAC), indicating toxicity may also be driven by reactive species generated upon device usage. Finally, non-toxic doses of either second or third generation condensate significantly blunted osteoblast osteoprotegerin secretion after 24 h, which was sustained for up to 7 days. In summary we demonstrate that e-cigarette vapour condensate, generated from commonly used second and third generation devices, can significantly reduce osteoblast viability and impair osteoblast function, at physiologically relevant doses. These data highlight the need for further investigation to inform users of the potential risks of e-cigarette use on bone health, including, accelerating bone associated disease progression, impacting skeletal development in younger users and to advise patients following orthopaedic surgery, dental surgery, or injury to maximise bone healing.

Changes in cellular metabolism have been implicated in mediating the activated fibroblast phenotype in a number of chronic inflammatory disorders, including pulmonary fibrosis, renal disease and rheumatoid arthritis. The aim of this study was therefore to characterise the metabolic profile of synovial joint fluid and synovial fibroblasts under both basal and inflammatory conditions in a cohort of obese and normal-weight hip OA patients. Furthermore, we sought to ascertain whether modulation of a metabolic pathway in OA synovial fibroblasts could alter their inflammatory activity. Synovium and synovial fluid was obtained from hip OA patients, who were either of normal-weight or obese and were undergoing elective joint replacement surgery. The synovial fluid metabolome was determined by 1H NMR spectroscopy. The metabolic profile of isolated synovial fibroblasts in vitro was characterised by lactate secretion, oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) using the Seahorse XF Analyser. The effects of a small molecule pharmacological inhibitor and siRNA targeted at glutaminase-1 (GLS1) were assessed to probe the role of glutamine metabolism in OA synovial fibroblast function. Obese OA patient synovial fluid (n = 5) exhibited a different metabotype, compared to normal-weight patient fluid (n = 6), with significantly increased levels of 1, 3-dimethylurate, N-Nitrosodimethylamine, succinate, tyrosine, pyruvate, glucose, glycine and lactate, and enrichment of the glutamine-glutamate metabolic pathway, which correlated with increasing adiposity. In vitro, isolated obese OA fibroblasts exhibited greater basal lactate secretion and aerobic glycolysis, and increased mitochondrial respiration when stimulated with pro-inflammatory cytokine TNFα, compared to fibroblasts from normal-weight patients. Inhibition of GLS1 attenuated the TNFα-induced expression and secretion of IL-6 in OA synovial fibroblasts. These findings suggest that altered cellular metabolism underpins the inflammatory phenotype of OA fibroblasts, and that targeted inhibition of glutamine-glutamate metabolism may provide a route to reducing the pathological effects of joint inflammation in OA patients who are obese.

Background: Synovial inflammation is associated with pain severity in patients with knee osteoarthritis (OA). The aim here was to determine in a population with knee OA, whether synovial tissue from areas associated with pain exhibited different synovial fibroblast subsets, compared to synovial tissue from sites not associated with pain. A further aim was to compare differences between early and end-stage disease synovial fibroblast subsets., Methods: Patients with early knee OA (n = 29) and end-stage knee OA (n = 22) were recruited. Patient reported pain was recorded by questionnaire and using an anatomical knee pain map. Proton density fat suppressed MRI axial and sagittal sequences were analysed and scored for synovitis. Synovial tissue was obtained from the medial and lateral parapatellar and suprapatellar sites. Fibroblast single cell RNA sequencing was performed using Chromium 10X and analysed using Seurat. Transcriptomes were functionally characterised using Ingenuity Pathway Analysis and the effect of fibroblast secretome on neuronal growth assessed using rat DRGN., Findings: Parapatellar synovitis was significantly associated with the pattern of patient-reported pain in knee OA patients. Synovial tissue from sites of patient-reported pain exhibited a differential transcriptomic phenotype, with distinct synovial fibroblast subsets in early OA and end-stage OA. Functional pathway analysis revealed that synovial tissue and fibroblast subsets from painful sites promoted fibrosis, inflammation and the growth and activity of neurons. The secretome of fibroblasts from early OA painful sites induced greater survival and neurite outgrowth in dissociated adult rodent dorsal root ganglion neurons., Interpretation: Sites of patient-reported pain in knee OA exhibit a different synovial tissue phenotype and distinct synovial fibroblast subsets. Further interrogation of these fibroblast pathotypes will increase our understanding of the role of synovitis in OA joint pain and provide a rationale for the therapeutic targeting of fibroblast subsets to alleviate pain in patients., Funding: This study was funded by Versus Arthritis, UK (21530; 21812)., Competing Interests: Declaration of Competing Interest SWJ declares grant funding from Versus Arthritis during the course of this study., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aims: The aim of our study was to investigate the effect of asymmetric crosslinked polyethylene liner use on the risk of revision of cementless and hybrid total hip arthroplasties (THAs)., Methods: We undertook a registry study combining the National Joint Registry dataset with polyethylene manufacturing characteristics as supplied by the manufacturers. The primary endpoint was revision for any reason. We performed further analyses on other reasons including instability, aseptic loosening, wear, and liner dissociation. The primary analytic approach was Cox proportional hazard regression., Results: A total of 213,146 THAs were included in the analysis. Overall, 2,997 revisions were recorded, 1,569 in THAs with a flat liner and 1,428 in THAs using an asymmetric liner. Flat liner THAs had a higher risk of revision for any reason than asymmetric liner THAs when implanted through a Hardinge/anterolateral approach (hazard ratio (HR) 1.169, 95% confidence interval (CI) 1.022 to 1.337) and through a posterior approach (HR 1.122, 95% CI 1.108 to 1.346). There was no increased risk of revision for aseptic loosening when asymmetric liners were used for any surgical approach. A separate analysis of the three most frequently used crosslinked polyethylene liners was in agreement with this finding. When analyzing THAs with flat liners only, THAs implanted through a Hardinge/anterolateral approach were associated with a reduced risk of revision for instability compared to posterior approach THAs (HR 0.561 (95% CI 0.446 to 0.706)). When analyzing THAs with an asymmetric liner, there was no significant difference in the risk of revision for instability between the two approaches (HR 0.838 (95% CI 0.633 to 1.110))., Conclusion: For THAs implanted through the posterior approach, the use of asymmetric liners reduces the risk of revision for instability and revision for any reason. In THAs implanted through a Hardinge/anterolateral approach, the use of an asymmetric liner was associated with a reduced risk of revision. The effect on revision for instability was less pronounced than in the posterior approach. Cite this article: Bone Joint J  2021;103-B(9):1479-1487.

Computer-assisted total hip arthroplasty (THA) is known to improve implantation precision, but clinical data demonstrating an improvement in survivorship and patient-reported outcome measures (PROMs) are lacking. Our aim was to compare the risk of revision, PROMs, and patient satisfaction between cohorts who underwent THA with and without the use of computer guidance., Methods: We used the data set and linked PROM data of the National Joint Registry of England, Wales, Northern Ireland and the Isle of Man. Our sample included THAs performed for osteoarthritis using cementless acetabular components from a single manufacturer (cementless and hybrid THAs). An additional analysis was performed limiting the sample size to cementless-only THAs. The primary end point was revision (any component) for any reason. Kaplan-Meier survivorship analysis and an adjusted Cox proportional-hazards model were used., Results: There were 41,683 non-computer-guided and 871 (2%) computer-guided cases included in our analysis of the cementless and hybrid group. There were 943 revisions in the non-computer-guided group and 7 in the computer-guided group. The cumulative revision rate at 10 years was 3.88% (95% confidence interval [CI]: 3.59% to 4.18%) for the non-computer-guided group and 1.06% (95% CI: 0.45% to 2.76%) for the computer-guided group. The Cox proportional-hazards model yielded a hazard ratio of 0.45 (95% CI: 0.21 to 0.96; p = 0.038). In the analysis of the cementless-only group, the cumulative revision rate at 10 years was 3.99% (95% CI: 3.62% to 4.38%) and 1.20% (95% CI: 0.52% to 3.12%) for the 2 groups, respectively. The Cox proportional-hazards model yielded a hazard ratio of 0.47 (95% CI: 0.22 to 1.01; p = 0.053). There was no significant difference in the 6-month Oxford Hip Score, the EuroQol-5 Dimension (EQ-5D) and EQ-VAS (Visual Analogue Scale) scores, and patient-reported success rates. Patient satisfaction (single-item satisfaction outcome measure) was higher in the computer-guided group, but this finding was limited by a reduced number of responses., Conclusions: In our analysis, the use of computer-guided surgery was associated with a lower rate of revision at mean follow-up of 5.6 years. This finding was upheld when the sample was restricted to cementless-only THAs. Causality cannot be inferred in view of the observational nature of the study, and additional studies are recommended to validate these findings., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSOA/A304)., (Copyright © 2021 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Obesity increases the risk of hip osteoarthritis (OA). Recent studies have shown that adipokine extracellular nicotinamide phosphoribosyltransferase (eNAMPT or visfatin) induces the production of IL-6 and matrix metalloproteases (MMPs) in chondrocytes, suggesting it may promote articular cartilage degradation. However, neither the functional effects of extracellular visfatin on human articular cartilage tissue, nor its expression in the joint of hip OA patients of varying BMI, have been reported. Hip OA joint tissues were collected from patients undergoing joint replacement surgery. Cartilage explants were stimulated with recombinant human visfatin. Pro-inflammatory cytokines and MMPs were measured by ELISA and Luminex. Localisation of visfatin expression in cartilage tissue was determined by immunohistochemistry. Cartilage matrix degradation was determined by quantifying proteoglycan release. Expression of visfatin was elevated in the synovial tissue of hip OA patients who were obese, and was co-localised with MMP-13 in areas of cartilage damage. Visfatin promoted the degradation of hip OA cartilage proteoglycan and induced the production of pro-inflammatory cytokines (IL-6, MCP-1, CCL20, and CCL4) and MMPs. The elevated expression of visfatin in the obese hip OA joint, and its functional effects on hip cartilage tissue, suggests it plays a central role in the loss of cartilage integrity in obese patients with hip OA.

Competing Interests: Intérêts concurrents : Aucun déclaré. Déclaration d’intérêts : Navindra Persaud est corédacteur pour le JAMC, mais n’a pas participé au processus ayant mené au choix de cet article.

Metastasis Associated Lung Adenocarcinoma Transcript-1 (MALAT1) is implicated in regulating the inflammatory response and in the pathology of several chronic inflammatory diseases, including osteoarthritis (OA). The purpose of this study was to examine the relationship between OA subchondral bone expression of MALAT1 with parameters of joint health and biomarkers of joint inflammation, and to determine its functional role in human OA osteoblasts. Subchondral bone and blood were collected from hip and knee OA patients ( n = 17) and bone only from neck of femur fracture patients ( n = 6) undergoing joint replacement surgery. Cytokines were determined by multiplex assays and ELISA, and gene expression by qPCR. MALAT1 loss of function was performed in OA patient osteoblasts using locked nucleic acids. The osteoblast transcriptome was analysed by RNASeq and pathway analysis. Bone expression of MALAT1 positively correlated to serum DKK1 and galectin-1 concentrations, and in OA patient osteoblasts was induced in response to IL-1β stimulation. Osteoblasts depleted of MALAT1 exhibited differential expression (>1.5 fold change) of 155 genes, including PTGS2. Both basal and IL-1β-mediated PGE2 secretion was greater in MALAT1 depleted osteoblasts. The induction of MALAT1 in human OA osteoblasts upon inflammatory challenge and its modulation of PGE2 production suggests that MALAT1 may play a role in regulating inflammation in OA subchondral bone.

Competing Interests: Intérêts concurrents: Diane Kelsall a été rédactrice en chef intérimaire du CMAJ jusqu’en octobre 2019; elle est actuellement rédactrice en chef du CMAJ Open et conseillère éditoriale pour le CMAJ. Gillian Leng est chef de la direction du National Institute for Health and Care Excellence, qui a une politique sur la déclaration et la gestion des conflits d’intérêts, et présidente du Guidelines International Network, qui propose des conseils sur la gestion des conflits d’intérêts potentiels. Brett Thombs, Ainsley Moore et Navindra Persaud sont respectivement président, viceprésidente et membre du Groupe d’étude canadien sur les soins de santé préventifs, qui élabore des guides de pratique clinique et a une politique sur la déclaration et la gestion des conflits d’intérêts. Navindra Persaud a reçu du financement des Instituts de recherche en santé du Canada, de l’Unité de soutien de la SRAP de l’Ontario et du Programme des chaires de recherche du Canada, indépendamment des travaux soumis. Holger Schünemann est membre du groupe de travail GRADE, principal auteur des principes sur la divulgation des intérêts du Guidelines International Network et auteur de correspondance de l’article sur l’outil PANELVIEW. Rachel Rodin et Marcello Tonelli ont reçu du financement des Instituts de recherche en santé du Canada pour la tenue de l’échange Meilleurs cerveaux mentionné dans l’article. Elie Akl a contribué à plusieurs études sur les conflits d’intérêts. G. Michael Allan a participé à la rédaction de lignes directrices. Il a reçu du soutien aux déplacements, des honoraires de conférencier et du soutien à la recherche. Ce financement été accordé par des sources sans but lucratif. Le Dr Allan n’a reçu aucun financement de l’industrie pharmaceutique. Isabelle Ganache a reçu des honoraires personnels de l’Institut national d’excellence santé et en services sociaux (INESSS) à titre de directrice du Bureau — Méthodologies et éthique (responsable des politiques institutionnelles sur la déclaration et la gestion des conflits d’intérêts) durant la réalisation de ce projet. Quinn Grundy a reçu des fonds du Conseil de recherches en sciences humaines et une bourse de recherche (Connaught New Research Award) de l’Université de Toronto, indépendamment des travaux soumis. Aucun autre intérêt concurrent n’a été déclaré. Déclarations d’intérêts: Diane Kelsall est conseillère éditoriale et Navindra Persaud, rédacteur associé pour le CMAJ. Ils n’ont toutefois pas participé au processus ayant mené au choix de cet article.

Background: Whilst bony fixation of hip replacement has stable solutions, there remains controversy over which bearing best optimizes longevity and function. Ceramic-on-ceramic (CoC) bearing combinations are associated with lower risk of revision due to aseptic loosening and dislocation. Evidence for long-term functional outcomes of modern, 4th generation CoC bearings is limited. The aim of this study was to analyze outcomes and complications of the R3™ Acetabular System (Smith & Nephew, Inc., Cordova, TN, USA) in combination with BIOLOX® Delta ceramic femoral head in patients undergoing primary total hip arthroplasty (THA)., Methods: Between June 2009 and May 2011, 175 patients (178 hips) were enrolled into a prospective, study at 6 sites in Europe and prospectively followed-up at 3 months and 1, 3, 5, and 7 years postoperative., Results: Total WOMAC score improved from 63 (range, 22-91) preoperative to 8 (range, 0-8) at 1-year follow-up and remained unchanged at 7-year follow-up. Modified Harris hip score improved from 45 (range, 10-87) preoperative to 83 (range, 25-100) at 3 months, 91 (range, 42-100) at 1 year, and 92 (range, 46, 100) at 7 years. UCLA Activity Rating Scale score improved from 3.3 (range, 1-8) preoperative to 6.2 (range, 2-8) at 1 year; it marginally declined to 5.8 (range, 3-8) at 7-year follow-up. There were 4 trochanteric fractures and 5 patients died of unrelated reasons. Three hips were revised (2 periprosthetic fractures and 1 subluxation). The 7-year cumulative survival rate was 98.3%., Conclusion: Clinical and functional improvements of THA with CoC bearing are maintained at 7 years postoperative., Trial Registration: ClinicalTrials.Gov, NCT03566082 , Registered 10 January 2018-retrospectively registered.

Background: Osteoarthritis is a prevalent condition in older adults that causes many patients to require a hip or knee replacement. Reducing patients' sedentariness prior to surgery may improve physical function and post-operative outcomes., Methods: We conducted a pragmatic randomised-controlled feasibility study with 2:1 allocation into intervention or usual care groups. The intervention, based on Self-Determination Theory, involved techniques to reduce sedentary behaviour, including motivational interviewing, setting of behavioural goals, and more. The primary outcome was feasibility, assessed using mixed methods. We included exploratory measures to inform a future definitive trial, such as ActivPal3 accelerometry to measure movement, the Short Physical Performance Battery (SPPB), Basic Psychological Needs, and cardiometabolic biomarkers. Assessments were at baseline, 1-week pre-surgery, and 6-week post-surgery., Results: We recruited 35 participants aged ≥ 60 years approximately 8 weeks before hip or knee arthroplasty. Participant uptake rate was 14.2%, and retention rate 85.7%. Participants were very satisfied with the study which was found to be feasible with some modifications. Exploratory within-group comparisons found that the intervention has potential to improve SPPB by 0.71 points from baseline to pre-surgery, a clinically significant increase, and reduce sedentary time by up to 66 min d -1 ., Conclusion: In this older surgical population, it is feasible to use behavioural techniques to displace sedentary time to activity and to conduct a trial spanning the period of surgical intervention. This may improve physical function and surgical outcomes. The INTEREST intervention is now ready for evaluation in a full-scale randomised-controlled trial., Registration: This trial was registered on Clinicaltrials.gov on 13/11/2018. ID: NCT03740412.