AimsThe aim of this study was to perform an incremental cost-utility analysis and assess the impact of differential costs and case volume on the cost-effectiveness of robotic arm-assisted medial unicompartmental knee arthroplasty (rUKA) compared to manual (mUKA).MethodsTen-year follow-up of patients who were randomized to rUKA (n = 64) or mUKA (n = 65) was performed. Patients completed the EuroQol five-dimension health questionnaire preoperatively, at three months, and one, two, five, and ten years postoperatively, which was used to calculate quality-adjusted life years (QALY) gained and the incremental cost-effectiveness ratio (ICER). Costs for the index and additional surgery and healthcare costs were calculated.ResultsmUKA had a lower survival for reintervention (84.8% (95% CI 76.2 to 93.4); p = 0.001), all-cause revision (88.9% (95% CI 81.3 to 96.5); p = 0.007) and aseptic revision (91.9% (95% CI 85.1 to 98.7); p = 0.023) when compared to the rUKA group at ten years, which was 100%. The rUKA group had a greater QALY gain per patient (mean difference 0.186; p = 0.651). Overall rUKA was the dominant intervention, being cost-saving and more effective with a greater health-related quality of life gain. On removal of infected reinterventions (n = 2), the ICER was £757 (not discounted) and £481 (discounted). When including all reintervention costs, rUKA was cost-saving when more than 100 robotic cases were performed per year. When removing the infected cases, rUKA was cost-saving when undertaking more than 800 robotic cases per year.ConclusionrUKA had lower reintervention and revision risks at ten years, which was cost-saving and associated with a greater QALY gain, and was the dominant procedure. When removing the cost of infection, which could be a random event, rUKA was a cost-effective intervention with an ICER (£757) which was lower than the willingness-to-pay threshold (£20,000).Cite this article: Bone Joint J 2025;107-B(1):72–80.
PURPOSE:The objective of this study was to compare the clinical outcomes 2 years following surgery between robotic-arm assisted bi-unicompartmental knee arthroplasty (bi-UKA) compared with conventional mechanically aligned total knee arthroplasty (TKA). METHODS:This is a single-centre, double-blinded, randomised controlled trial comparing bi-UKA and TKA. Patient-reported outcome measures (PROMs) were collected from 60 patients (27 bi-UKA and 33 TKA patients) 2 years following surgery, including Oxford Knee Score (OKS), New Knee Society Score (NKSS), Forgotten Joint Score, EQ-5D-3L, UCLA activity scale, Hospital Anxiety and Depression Scale, Pain and Stiffness Visual Analogue Scales, Satisfaction and Range of Motion. Complications were also recorded at each visit. RESULTS:TKA and bi-UKA continue to offer comparable PROMs. The clinical NKSS demonstrated a significant difference between the two interventions, TKA 59.5 (37-65) versus bi-UKA 26.0 (22-40) (p < 0.001). There were no significant differences shown between the interventions across all time points and remaining outcome measures (OKS at 2-year follow-up; TKA-42.0 [34.0-45.5] vs. bi-UKA-41.0 [28.0-45.0]) or the proportion of participant achieving bi-phasic gait at 2 years following surgery (p = 0.429). There was no difference in complication rates following surgery at 2 years. CONCLUSION:Robotic arm-assisted, cruciate-sparing bi-UKA and mechanically aligned TKA offer similar clinical outcomes 2 years following surgery with no difference in complication rates. Further, follow-up is required to monitor patients as they enter mid/long-term follow-up and determine whether patients will gain long-term benefits from the cruciate-sparing bi-UKA approach. LEVEL OF EVIDENCE:Level I.
Aims The aim of this study was to perform an incremental costutility analysis and assess the impact of differential costs and case volume on the costeffectiveness of robotic arm- assisted medial unicompartmental knee arthroplasty (rUKA) compared to manual (mUKA). Methods Ten- year follow- up of patients who were randomized to rUKA (n = 64) or mUKA (n = 65) was performed. Patients completed the EuroQol five- dimension health questionnaire preoperatively, at three months, and one, two, five, and ten years postoperatively, which was used to calculate quality- adjusted life years (QALY) gained and the incremental costeffectiveness ratio (ICER). Costs for the index and additional surgery and healthcare costs were calculated. Results mUKA had a lower survival for reintervention (84.8% (95% CI 76.2 to 93.4); p = 0.001), all- cause revision (88.9% (95% CI 81.3 to 96.5); p = 0.007) and aseptic revision (91.9% (95% CI 85.1 to 98.7); p = 0.023) when compared to the rUKA group at ten years, which was 100%. The rUKA group had a greater QALY gain per patient (mean difference 0.186; p = 0.651). Overall rUKA was the dominant intervention, being costsaving and more effective with a greater health- related quality of life gain. On removal of infected reinterventions (n = 2), the ICER was 757 pound (not discounted) and 481 pound (discounted). When including all reintervention costs, rUKA was costsaving when more than 100 robotic cases were performed per year. When removing the infected cases, rUKA was costsaving when undertaking more than 800 robotic cases per year. Conclusion rUKA had lower reintervention and revision risks at ten years, which was costsaving and associated with a greater QALY gain, and was the dominant procedure. When removing the cost of infection, which could be a random event, rUKA was a costeffective intervention with an ICER (757) pound which was lower than the willingness- to- pay threshold (20,000) pound.
Common ash (Fraxinus excelsior) is under intensive attack from the invasive alien pathogenic fungus Hymenoscyphus fraxineus, causing ash dieback at epidemic levels throughout Europe. Previous studies have found significant genetic variation among genotypes in ash dieback susceptibility and that host phenology, such as autumn yellowing, is correlated with susceptibility of ash trees to H. fraxineus; however, the genomic basis of ash dieback tolerance in F. excelsior requires further investigation. Here, we integrate quantitative genetics based on multiple replicates and genome-wide association analyses with machine learning to reveal the genetic architecture of ash dieback tolerance and of phenological traits in F. excelsior populations in six European countries (Austria, Denmark, Germany, Ireland, Lithuania, Sweden). Based on phenotypic data of 486 F. excelsior replicated genotypes we observed negative genotypic correlations between crown damage caused by ash dieback and intensity of autumn leaf yellowing within multiple sampling sites. Our results suggest that the examined traits are polygenic and using genomic prediction models, with ranked single nucleotide polymorphisms (SNPs) based on GWAS associations as input, a large proportion of the variation was predicted by unlinked SNPs. Based on 100 unlinked SNPs, we can predict 55% of the variation in disease tolerance among genotypes (as phenotyped in genetic trials), increasing to a maximum of 63% when predicted from 9155 SNPs. In autumn leaf yellowing, 52% of variation is predicted by 100 unlinked SNPs, reaching a peak of 72% using 3740 SNPs. Based on feature permutations within genomic prediction models, a total of eight nonsynonymous SNPs linked to ash dieback crown damage and autumn leaf yellowing (three and five SNPs, respectively) were identified, these were located within genes related to plant defence (pattern triggered immunity, pathogen detection) and phenology (regulation of flowering and seed maturation, auxin transport). We did not find an overlap between genes associated with crown damage level and autumn leaf yellowing. Hence, our results shed light on the difference in the genomic basis of ADB tolerance and autumn leaf yellowing despite these two traits being correlated in quantitative genetic analysis. Overall, our methods show the applicability of genomic prediction models when combined with GWAS to reveal the genomic architecture of polygenic disease tolerance enabling the identification of ash dieback tolerant trees for breeding or conservation purposes.
The parasitic worm-derived immunomodulator, ES-62 rescues defective levels of IL-10-producing regulatory B cells (Bregs) and suppresses chronic Th1/Th17-driven inflammation to protect against joint destruction in the mouse collagen-induced arthritis (CIA) model of rheumatoid arthritis. Such autoimmune arthritis is also associated with dysbiosis of the gut microbiota and disruption of intestinal barrier integrity. We recently further exploited the CIA model to show that ES-62’s prevention of joint destruction is associated with protection of intestinal barrier integrity and normalization of the gut microbiota, thereby suppressing the gut pathology that precedes the onset of autoimmunity and joint damage in CIA-mice. As the status of the gut microbiota impacts on immune responses by influencing haematopoiesis, we have therefore investigated whether ES-62 harnesses the homeostatic mechanisms regulating this gut-bone marrow (BM) axis to resolve the chronic inflammation promoting autoimmunity and joint destruction in CIA. Reflecting this, ES-62 was found to counteract the BM myeloid/lymphoid bias typically associated with chronic inflammation and infection. This was achieved primarily by ES-62 acting to maintain the levels of lymphoid lineages (B220+ and CD3+ cells) observed in naïve, healthy mice but lost from the BM of CIA-mice. Moreover, ES-62’s ability to prevent bone-destroying osteoclastogenesis was found to be associated with its suppression of CIA-induced upregulation of osteoclast progenitors (OCPs) in the BM. Critically, and supporting ES-62’s targeting of the gut-BM axis, this rewiring of inflammatory haematopoiesis was lost in mice with a depleted microbiome. Underlining the importance of ES-62’s actions in restoring steady-state haematopoiesis, the BM levels of B and T lymphoid cells were shown to be inversely correlated, whilst the levels of OCPs positively correlated, with the severity of joint damage in CIA-mice.
Osteoporosis is a major risk factor for fragility fractures. The British Orthopaedics Association Standards for Trauma and Orthopaedics (BOAST) and Getting it Right First Time (GIRFT) guidelines on fragility fracture management highlight the need to initiate prompt, coordinated multidisciplinary care with a focus on early mobilisation to improve patient outcomes. Medical management of fragility fractures focuses on the prevention of progressive frailty. Advancements in medical therapy include romosozumab, recommended by the National Institute for Health and Care Excellence guidance in patients with imminent fracture risk, which improves overall bone mineral density. Regional nerve blocks are an increasingly common form of perioperative anaesthesia with fewer side effects than opioids and rates of postoperative delirium. Surgical management of osteoporotic fractures poses unique challenges, such as complex fracture patterns and increased risk of implant failure. The surgical approach to fragility fractures has undergone major advancements over the past 20 years, with developments such as polyaxial locking and far cortical locking systems that achieve secondary bone healing, as well as cement augmented screw fixation to provide stable fixation in osteoporotic bone. The development of minimally invasive surgical approaches has led to improved periosteal blood flow around a fracture site, as well as reduced operating time, hospital stay, and time to pain-free weight-bearing. In the future, we are likely to see a focus on minimally invasive surgical techniques for vertebral and pelvic fragility fractures to improve patients' mobility and independence before discharge, subsequently improving quality of life and preventing progressive frailty.
Aims:Limb salvage surgery (LSS) is the primary treatment option for primary bone malignancy. It involves the removal of bone and tissue, followed by reconstruction with endoprosthetic replacements (EPRs) to prevent amputation. Trabecular metal (TM) collars have been developed to encourage bone ingrowth (osseointegration (OI)) into EPRs. The primary aim of this study was to assess whether OI occurs when TM collars are used in EPRs for tumour. Methods:A total of 124 patients from July 2010 to August 2021 who underwent an EPR for tumour under the West of Scotland orthopaedic oncology team were identified. Overall, 81 patients (65%) met the inclusion criteria, and two consultants independently analyzed radiographs at three and 12 months, as well as the last radiograph, using a modified version of the Stanford Radiological Assessment System. Results:OI of the TM collar occurred in approximately 65% of patients at last radiograph. The percentage of patients with OI at three months (65.4%) reflected the 12-month (65%) and long-term (64.4%) follow-up. The median amount of OI across all radiographs was one at all three timepoints, with only five cases (11.1%) showing OI in all four zones at last radiograph. Radiolucency at the bone:collar junction was present in 23 cases (28.4%) at three months, but only four (6.7%) showed progression of this at 12 months. The interobserver reliability was found to be highly reliable in all parameters (p < 0.001). Conclusion:OI occurs in approximately 65% of TM collars, and is similar at three months, 12 months, and last radiograph. The extent of OI at the bone:collar junction was found to have decreased at longer-term follow-up. Furthermore, radiolucency at the bone-collar impact junction does occur in some patients but only a low number will show radiolucency progression at longer-term follow-up.
The Bass Becking and Beijerinck theory of the microbial world that 'everything is everywhere but the environment selects' has provided a basis to test microbial ecological theory for almost a century. Applying theory to the apparent chaos of the microbial world is arduous, and applying rules that guide our understanding is difficult. The Bass Becking and Beijerinck theory attempts to explain microbial community structure, i.e. why are certain microbes in a given environment? And why is a particular environment populated by certain microbes? Since the theory was advanced, limitations have been found. In particular, the advent of next-generation sequencing in the 2000s has amplified our ability to categorize and quantify the microbial world. Despite evident limitations demonstrating that the Bass Becking and Beijerinck theory is an oversimplification, it is perhaps the most unifying theory within microbial ecology.
Objective The endophytic mycobiome is present in all studied plant compartments, including fruits and seeds. Here, we studied the mycobiome of seed wings as they are transferred with seeds in common ash and tested whether the mycobiome differs among trees. To achieve this, we used ITS1-based amplicon sequencing and two genotypes of F. excelsior as a model to compare the mycobiome of mother trees and their wings. Results We compared the mycobiome of 57 seed wings to the seed stalks (57) collected from two genotypes of F. excelsior using three ramets of each genotype. Alpha diversity indices (ACE, Fisher and Observed OTUs) suggested a higher richness of the mycobiome associated with the seed wing than the seed stalk within each genotype. However, there were neither significant differences in Shannon diversity between the mycobiomes from the two tissue types nor the two genotypes. PERMANOVA revealed significant differences in the mycobiome composition between tissue types (P < 0.001). It also showed a significant difference between seed wings (P = 0.04), but not between seed stalks of the two genotypes. Our results suggest that Fraxinus excelsior mother trees disperse different sets of mycobiomes with their seed wings, which may be important for germination and seedling establishment-especially in the light of ash dieback.
ES-62, a protein secreted by Acanthocheilonema viteae, is anti-inflammatory by virtue of covalently attached phosphorylcholine (PC) residues and thus a library of drug-like small molecule analogues (SMAs) based on its PC moieties has been designed for therapeutic purposes. Two members, SMAs 11a and 12b, were previously found to suppress production of pro-inflammatory cytokines by mouse bone marrow-derived macrophages (BMMs) exposed to cytosine-phosphate-guanosine oligodeoxynucleotides (CpG), agonists for Toll-like receptor 9. In order to explore the mechanism of action underlying such activities, an untargeted mass spectrometry-based metabolomics screen was undertaken. Stimulation of BMMs with CpG produced significant metabolic changes relating to glycolysis and the TCA cycle but the SMAs had little impact on this. Also, the SMAs did not promote alterations in metabolites known to be associated with macrophage M1/M2 polarization. Rather, BMMs exposed to SMAs 11a or 12b prior to CpG treatment, or even alone, revealed downregulation of metabolites of creatine, a molecule whose major role is in the transport of high energy phosphate from the mitochondria to the cytosol. These data therefore provide insight into a possible mechanism of action of molecules with significant therapeutic potential that has not previously been described for parasitic worm products.
Introduction: Tibial plateau fractures are complex, peri-articular fractures that can have poor outcomes resulting in conversion to total knee arthroplasty (TKA). This study evaluates the 10-year survival of tibial plateau fractures treated with open reduction and internal fixation and identifies risk factors associated with conversion to TKA. Methods: This retrospective cohort study evaluates the outcomes of 126 patients undergoing tibial plateau ORIF from January 2011 to December 2012 at Glasgow Royal Infirmary. As well as patient factors, radiographic assessments were analysed including the degree of articular depression, medial proximal tibial angle, and femoral width ratio preoperatively, peri-operatively and at the time of union. Patients requiring further surgical intervention, including TKA, were evaluated further. Results: A bell-shaped distribution of patient age was observed. Schatzker II fractures were most prevalent (48%). Pre-operative articular depression averaged 6.9 mm ranging from 0.0 - 36.0 mm. Operative reduction was generally satisfactory (mean articular depression 1.3 mm, femoral width 0.96, mPTA 89.6(0)), with 82% achieving an anatomical reduction. 12 patients (9.3%) required TKA during follow-up with Kaplan-Meier calculated as 91.9% at 5 years and 87.4% at 10 years. Articular depression > 4 mm (HR = 16.2), femoral width ratio > 1.05 (HR = 14.7) and age > 50 years (HR = 4.2) at time for fracture union were independently associated with progression to TKA. Conclusion: 9.3% of patients required TKA within 10 years of tibial plateau ORIF, Kaplan Meier 10-year survivorship was 87.4%. Joint depression and increased tibial width at time of union and age were independent risk factors associated with need for TKA. Particular care must be taken during operative intervention to ensure adequate reduction to lower this risk. Crown Copyright (c) 2024 Published by Elsevier B.V. All rights reserved.
Abstract Aim This study represents one of the largest clinical case series' evaluating long-term outcomes following surgical fixation of tibial plateau fractures over a 10-year follow-up. The primary aim is to evaluate the incidence of TKR and risk-factors associated with poor outcomes. Method Patients receiving surgical fixation of tibial plateau fractures between 2008 – 2012 were included. Those requiring arthroplasty or endoprosthesis post-injury were excluded. PACs was used to analyse case notes and radiographic imaging. Articular reduction and alignment (mPTA) were measured using pre-operative radiographs. Comparisons were made with radiographs post-fracture union (6-weeks to 6-months), assessing fracture reduction maintenance. Long-term outcomes were assessed for patients receiving imaging thereafter. Patients were checked using the Scottish National Imaging Archive. Results 130 patients presented various fractures (Schatzker I-III n = 78, IV n = 12, V n = 9, VI n = 29) and 2 open-fractures. 32 patients required further surgery, 13 required multiple operations - resulting in 47 operations. These included metalwork removal (n = 28, 21.5%), TKR (n = 12, 9.2%), washout for infection (n = 3, 2.3%), osteotomy (n = 2, 1.5%), sequestrectomy (n = 1, 0.8%), and above knee amputation (n = 1, 0.8%). ≥ 2mm articular reduction was maintained in the majority (84%); however, good articular reduction did not prevent progression to arthroplasty (average step 1.4mm in TKR versus 1.8mm in non-TKR). Good alignment correlated with favourable outcomes - average mPTA being 90.8° in non-TKR versus 93.5° in TKR. Conclusions These findings support previous literature in this field demonstrating that malalignment, rather than articular depression, increases the risk for post-traumatic arthritis requiring arthroplasty. The incidence of TKR after tibial plateau fracture fixation at 10-years was 9.2%.
Mice develop pathology in the lungs as they age and this may be accelerated by a high calorie diet (HCD). ES-62 is a protein secreted by the parasitic worm Acanthocheilonema viteae that is immunomodulatory by virtue of covalently attached phosphorylcholine (PC) moieties. In this study, we show that weekly treatment of C57BL/6J mice with ES-62 protected against pathology in the lungs in male but not female mice fed a HCD from 10 weeks of age as shown by reductions in cellular infiltration and airway remodelling, particularly up to 160 days of age. ES-62 also reduced gene expression of the cytokines IL-4 and IL-17 and in addition the TLR/IL-1R adaptor MyD88, in the lungs of male mice although HCD-induced increases in these inflammatory markers were not detected until between 340 and 500 days of age. A combination of two drug-like ES-62 PC-based small molecule analogues (SMAs), produced broadly similar protective effects in the lungs of male mice with respect to both lung pathology and inflammatory markers, in addition to a decrease in HCD-induced IL-5 expression. Overall, our data show that ES-62 and its SMAs offer protection against HCD-accelerated pathological changes in the lungs during ageing. Given the targeting of Th2 cytokines and IL-17, we discuss this protection in the context of ES-62’s previously described amelioration of airway hyper-responsiveness in mouse models of asthma.
PurposeThis study was to evaluate the survivorship of HTO for the treatment of medial compartment osteoarthritis (OA) in young and active patients from two teaching hospitals in a single city.MethodsThis is a retrospective cohort multicenter study looking at HTO for treatment of medial compartment OA. We analyzed a case series of HTO's performed by four surgeons in two centres over a 14-year period. Failure was defined as conversion to total knee replacement (TKR). All cases where additional procedures for instability of the knee were performed at the time of the index surgery were excluded. Time to failure was recorded, and a Kaplan-Meir (KM) analysis was performed to evaluate survivorship. Univariate binary regression analysis was undertaken to identify associations between risk factors and failure.ResultsA total of 96 patients were included in the study with a median age was 45 years. The survivorship at five years post-op was 90.3%, and at ten years post-op, it was 82%. Patients that were 14 years after surgery had a survivorship of 65%. Also, 18.8% of patients required the removal of their metalwork. The overall complication rate was 6.3%. The univariate regression analysis showed that higher age (p = 0.02) and larger corrections requiring the use of bone graft increased the risk of failure (p = 0.02). There was no statistically significant correlation between laterality, gender, complication rate, and pre-operative alignment to survivorship.ConclusionThis is one of the largest reported case series of HTO's with comparable survivorship at five and ten year follow-up compared to the reported literature. There was an association found between increasing age and larger corrections requiring bone graft at index procedure to increasing failure rate.
Computer-assisted surgery (CAS) total knee arthroplasty (TKA) remains a controversial area of surgical practice. The aim of this study is to report the ten-year revision rates and patient-reported outcome measures (PROMS) of a single-blinded, prospective, randomised controlled trial comparing electromagnetically (EM) navigated and conventional TKA. 199 patients were randomised to receive either EM navigated or conventional TKA where the aim of implantation was neutral mechanical alignment in all cases. Ten-year revision rates were collated and compared between the two intervention groups. Longitudinal PROMS data was collected prospectively at various time points up to 10 years post-operatively. Over the ten-year period, there were 23 deaths (22.8
Pest insects and microbial pathogens threaten agricultural crop productivity and global forest biomes, and insect-microbe interactions can increase the severity of plant decline. Whilst bacterial chemicals have been shown to influence insect behaviour, the impact of insect-derived chemistries on phytopathogens is barely understood. Here, we investigated beetle larvae-bacteria interactions in acute oak decline (AOD), a decline disease of oak characterised by inner bark necrosis caused by a polymicrobial consortium including Brenneria goodwinii and larval galleries of Agrilus biguttatus . To test the hypothesis that larval chemicals influence the activity of B. goodwinii , we extracted A. biguttatus larvae and tested the effect of extracts on the growth and gene expression of B. goodwinii in vitro . We demonstrate that larval chemicals elicit increased bacterial growth rate and final cell density, as well as differential expression of almost 800 genes, including the Type III Secretion System and its effectors, major virulence factors in other plant pathogens. Contrastingly, gallery woody-tissue extracts induced no such effects. Our work highlights the importance of multi-kingdom interactions in plant disease and demonstrate a novel mode-of-action for insect-derived chemical elicitors in facilitating the virulence of phytopathogens, which may be important in understanding plant diseases globally.
European ash, Fraxinus excelsior is facing the double threat of ongoing devastation by the invasive fungal pathogen, Hymenoscyphus fraxineus and the imminent arrival of the non-native emerald ash borer (EAB), Agrilus planipennis . The spread of EAB which is currently moving westwards from European Russia and Ukraine into central Europe, poses an additional substantial threat to European ash, F. excelsior . While the molecular basis for resistance or variation in resistance among European ash genotypes is heavily investigated, comparatively little is known about the molecular ash traits involved in resistance against EAB. In this study we have gathered transcriptomic data from EAB inoculated genotypes of F. excelsior that have previously shown different levels of susceptibility to EAB. Resultant datasets show differential gene expression in susceptible and resistant genotypes in response to EAB infestation. This data will provide important information on the molecular basis of resistance to the EAB and allow the development of management plans to combat a pending threat of a culturally and ecologically important European tree species.
Objective IĸB protein B cell lymphoma 3‐encoded protein (BCL3) is a regulator of the NF‐κB family of transcription factors. NF‐κB signaling fundamentally influences the fate of bone‐forming osteoblasts and bone‐resorbing osteoclasts, but the role of BCL3 in bone biology has not been investigated. The objective of this study was to evaluate BCL3 in skeletal development, maintenance, and osteoarthritic pathology. Methods To assess the contribution of BCL3 to skeletal homeostasis, neonatal mice (n = 6–14) lacking BCL3 ( Bcl3 −/− ) and wild‐type (WT) controls were characterized for bone phenotype and density. To reveal the contribution to bone phenotype by the osteoblast compartment in Bcl3 −/− mice, transcriptomic analysis of early osteogenic differentiation and cellular function (n = 3–7) were assessed. Osteoclast differentiation and function in Bcl3 −/− mice (n = 3–5) was assessed. Adult 20‐week Bcl3 −/− and WT mice bone phenotype, strength, and turnover were assessed. A destabilization of the medial meniscus model of osteoarthritic osteophytogenesis was used to understand adult bone formation in Bcl3 −/− mice (n = 11–13). Results Evaluation of Bcl3 −/− mice revealed congenitally increased bone density, long bone dwarfism, increased bone biomechanical strength, and altered bone turnover. Molecular and cellular characterization of mesenchymal precursors showed that Bcl3 −/− cells displayed an accelerated osteogenic transcriptional profile that led to enhanced differentiation into osteoblasts with increased functional activity, which could be reversed with a mimetic peptide. In a model of osteoarthritis‐induced osteophytogenesis, Bcl3 −/− mice exhibited decreased pathological osteophyte formation ( P < 0.05). Conclusion Cumulatively, these findings demonstrate that BCL3 controls developmental mineralization to enable appropriate bone formation, whereas in a pathological setting, it contributes to skeletal pathology. image
AimsTo perform an incremental cost-utility analysis and assess the impact of differential costs and case volume on the cost-effectiveness of robotic arm-assisted unicompartmental knee arthroplasty (rUKA) compared to manual (mUKA).MethodsThis was a five-year follow-up study of patients who were randomized to rUKA (n = 64) or mUKA (n = 65). Patients completed the EuroQol five-dimension questionnaire (EQ-5D) preoperatively, and at three months and one, two, and five years postoperatively, which was used to calculate quality-adjusted life years (QALYs) gained. Costs for the primary and additional surgery and healthcare costs were calculated.ResultsrUKA was associated with a relative 0.012 QALY gain at five years, which was associated with an incremental cost per QALY of £13,078 for a unit undertaking 400 cases per year. A cost per QALY of less than £20,000 was achieved when ≥ 300 cases were performed per year. However, on removal of the cost for a revision for presumed infection (mUKA group, n = 1) the cost per QALY was greater than £38,000, which was in part due to the increased intraoperative consumable costs associated with rUKA (£626 per patient). When the absolute cost difference (operative and revision costs) was less than £240, a cost per QALY of less than £20,000 was achieved. On removing the cost of the revision for infection, rUKA was cost-neutral when more than 900 cases per year were undertaken and when the consumable costs were zero.ConclusionrUKA was a cost-effective intervention with an incremental cost per QALY of £13,078 at five years, however when removing the revision for presumed infection, which was arguably a random event, this was no longer the case. The absolute cost difference had to be less than £240 to be cost-effective, which could be achieved by reducing the perioperative costs of rUKA or if there were increased revision costs associated with mUKA with longer follow-up.Cite this article: Bone Jt Open 2023;4(11):889–899.
Aims To perform an incremental cost-utility analysis and assess the impact of differential costs and case volume on the cost-effectiveness of robotic arm-assisted unicompartmental knee arthroplasty (rUKA) compared to manual (mUKA).Methods This was a five year follow up study of patients who were randomized to rUKA (n = 64) or mUKA (n = 65). Patients completed the EuroQol five-dimension questionnaire (EQ- 5D) preoperatively, and at three months and one, two, and five years postoperatively, which was used to calculate quality-adjusted life years (QALYs) gained. Costs for the primary and additional surgery and healthcare costs were calculated.Results rUKA was associated with a relative 0.012 QALY gain at five years, which was associated with an incremental cost per QALY of 13,078 pound for a unit undertaking 400 cases per year. A cost per QALY of less than 20,000 pound was achieved when >= 300 cases were performed per year. However, on removal of the cost for a revision for presumed infection (mUKA group, n = 1) the cost per QALY was greater than 38,000 pound, which was in part due to the increased intraoperative consumable costs associated with rUKA (626 pound per patient). When the absolute cost difference (operative and revision costs) was less than 240 pound, a cost per QALY of less than 20,000 pound was achieved. On removing the cost of the revision for infection, rUKA was cost-neutral when more than 900 cases per year were undertaken and when the consumable costs were zero.Conclusion rUKA was a cost-effective intervention with an incremental cost per QALY of 13,078 pound at five years, however when removing the revision for presumed infection, which was arguably a random event, this was no longer the case. The absolute cost difference had to be less than 240 pound to be cost-effective, which could be achieved by reducing the perioperative costs of rUKA or if there were increased revision costs associated with mUKA with longer follow up.