Aim. Mesenchymal stem cells (MSCs) have several properties that may support their use as an early treatment option for osteoarthritis (OA). This study investigated the role of multiple injections of allogeneic bone marrow-derived stem cells (BMSCs) to alleviate the progression of osteoarthritic changes in the various structures of the mature rabbit knee in an anterior cruciate ligament (ACL)-deficient OA model. Materials and Methods. Two months after bilateral section of the ACL of Japanese white rabbits aged nine months or more, either phosphate buffered saline (PBS) or 1 x 10. 6. MSCs were injected into the knee joint in single or three consecutive doses. After two months, the articular cartilage and meniscus were assessed macroscopically, histologically, and immunohistochemically using collagen I and II. Results. Within the PBS injection (control group), typical progressive degenerative changes were revealed in the various knee structures. In the single MSC injection (single group), osteoarthritic changes were attenuated, but still appeared, especially in the medial compartments involving fibrillation of the articular cartilage, osteophyte formation in the medial plateau, and longitudinal tear of the meniscus. In the multiple-injections group, the smoothness and texture of the articular cartilage and meniscus were improved. Histologically, absence or reduction in matrix staining and cellularity were noticeable in the control and single-injection groups, respectively, in contrast to the multiple-injections group, which showed good intensity of matrix staining and chondrocyte distribution in the various cartilage zones. Osteoarthritis Research Society International (OARSI) scoring showed significantly better results in the multiple-injections group than in the other groups. Immunohistochemically, collagen I existed superficially in the medial femoral condyle in the single group, while collagen II was more evident in the multiple-injections group than the single-injection group. Conclusion. A single injection of MSCs was not enough to restore the condition of osteoarthritic joints. This is in contrast to multiple injections of MSCs, which had the ability to replace lost cells, as well as reducing inflammation. Cite this article: Bone Joint J 2019;101-B:824–831

Aims. Platelet-rich plasma (PRP) intra-articular injections may provide a simple and minimally invasive treatment for early-stage knee osteoarthritis (OA). This has led to an increase in its adoption as a treatment for knee OA, although there is uncertainty about its efficacy and benefit. We hypothesized that patients with early-stage symptomatic knee OA who receive multiple PRP injections will have better clinical outcomes than those receiving single PRP or placebo injections. Methods. A double-blinded, randomized placebo-controlled trial was performed with three groups receiving either placebo injections (Normal Saline), one PRP injection followed by two placebo injections, or three PRP injections. Each injection was given one week apart. Outcomes were prospectively collected prior to intervention and then at six weeks, three months, six months, and 12 months post-intervention. Primary outcome measures were Knee Injury and Osteoarthritis Outcome Score (KOOS) and EuroQol five-dimension five-level index (EQ-5D-5L). Secondary outcomes included visual analogue scale for pain and patient subjective assessment of the injections. Results. A total of 102 patients were recruited. The follow-up period was 12 months, at intervals of six weeks, 12 weeks, six months, and 12 months. KOOS-Total significantly improved in all groups at these time intervals compared to pre-injection. There was an improvement in EQ-5D-5L index scores in saline and single injection groups, but not in the multiple injection group. Comparison of treatment groups showed no additional beneficial effect of single or multiple PRP injections above that displayed in the saline injection group. Subjective patient satisfaction and recommendation of treatment received demonstrated a similar pattern in all the groups. There was no indication of superiority of either single or multiple PRP injections compared to saline injections. Conclusion. There is no evidence that single or multiple PRP had any additional beneficial effect compared to saline injection up to 12 months, follow-up after treatment of early stage symptomatic OA of the knee. Cite this article: Bone Joint J 2022;104-B(6):663–671

Aims. The aim of this study was to estimate the incremental use of resources, costs, and quality of life outcomes associated with surgical reconstruction compared to rehabilitation for long-standing anterior cruciate ligament (ACL) injury in the NHS, and to estimate its cost-effectiveness. Methods. A total of 316 patients were recruited and randomly assigned to either surgical reconstruction or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment). Healthcare resource use and health-related quality of life data (EuroQol five-dimension five-level health questionnaire) were collected in the trial at six, 12, and 18 months using self-reported questionnaires and medical records. Using intention-to-treat analysis, differences in costs, and quality-adjusted life years (QALYs) between treatment arms were estimated adjusting for baseline differences and following multiple imputation of missing data. The incremental cost-effectiveness ratio (ICER) was estimated as the difference in costs divided by the difference in QALYs between reconstruction and rehabilitation. Results. At 18 months, patients in the surgical reconstruction arm reported higher QALYs (0.052 (95% confidence interval (CI) -0.012 to 0.117); p = 0.177) and higher NHS costs (£1,017 (95% CI 557 to 1,476); p < 0.001) compared to rehabilitation. This resulted in an ICER of £19,346 per QALY with the probability of surgical reconstruction being cost-effective of 51% and 72% at a willingness-to-pay threshold of £20,000 and £30,000 per QALY, respectively. Conclusion. Surgical reconstruction as a management strategy for patients with long-standing ACL injury is more effective, but more expensive, at 18 months compared to rehabilitation management. In the UK setting, surgical reconstruction is cost-effective. Cite this article: Bone Joint J 2024;106-B(1):38–45

Aims. To identify unanswered questions about the prevention, diagnosis, treatment, and rehabilitation and delivery of care of first-time soft-tissue knee injuries (ligament injuries, patella dislocations, meniscal injuries, and articular cartilage) in children (aged 12 years and older) and adults. Methods. The James Lind Alliance (JLA) methodology for Priority Setting Partnerships was followed. An initial survey invited patients and healthcare professionals from the UK to submit any uncertainties regarding soft-tissue knee injury prevention, diagnosis, treatment, and rehabilitation and delivery of care. Over 1,000 questions were received. From these, 74 questions (identifying common concerns) were formulated and checked against the best available evidence. An interim survey was then conducted and 27 questions were taken forward to the final workshop, held in January 2023, where they were discussed, ranked, and scored in multiple rounds of prioritization. This was conducted by healthcare professionals, patients, and carers. Results. The top ten included questions regarding prevention, diagnosis, treatment, and rehabilitation. The number one question was, ‘How urgently do soft-tissue knee injuries need to be treated for the best outcome?’. This reflects the concerns of patients, carers, and the wider multidisciplinary team. Conclusion. This validated process has generated ten important priorities for future soft-tissue knee injury research. These have been submitted to the National Institute for Health and Care Research. All 27 questions in the final workshop have been published on the JLA website. Cite this article: Bone Joint J 2024;106-B(3):232–239

Aims. This study aims to determine difference in annual rate of early-onset (≤ 90 days) deep surgical site infection (SSI) following primary total knee arthroplasty (TKA) for osteoarthritis, and to identify risk factors that may be associated with infection. Methods. This is a retrospective population-based cohort study using prospectively collected patient-level data between 1 January 2013 and 1 March 2020. The diagnosis of deep SSI was defined as per the Centers for Disease Control/National Healthcare Safety Network criteria. The Mann-Kendall Trend test was used to detect monotonic trends in annual rates of early-onset deep SSI over time. Multiple logistic regression was used to analyze the effect of different patient, surgical, and healthcare setting factors on the risk of developing a deep SSI within 90 days from surgery for patients with complete data. We also report 90-day mortality. Results. A total of 39,038 patients underwent primary TKA for osteoarthritis during the study period. Of these, 275 patients developed a deep SSI within 90 days of surgery, representing a cumulative incidence of 0.7%. The annual infection rate did not significantly decrease over the seven-year study period (p = 0.162). Overall, 13,885 (35.5%) cases were excluded from the risk analysis due to missing data. Risk factors associated with early-onset deep SSI included male sex, American Society of Anesthesiologists grade ≥ 3, blood transfusion, acute length of stay, and surgeon volume < 30 TKAs/year. Early-onset deep SSI was not associated with increased 90-day mortality. Conclusion. This study establishes a reliable baseline infection rate for early-onset deep SSI after TKA for osteoarthritis using robust Infection Prevention and Control surveillance data, and identifies several potentially modifiable risk factors. Cite this article: Bone Joint J 2023;105-B(9):971–976

Aims. Knee osteoarthritis (OA) is characterized by a chronic inflammatory process involving multiple cytokine pathways, leading to articular cartilage degeneration. Intra-articular therapies using pharmaceutical or autologous anti-inflammatory factors offer potential non-surgical treatment options. Autologous protein solution (APS) is one such product that uses the patient’s blood to produce a concentrate of cells and anti-inflammatory cytokines. This study evaluated the effect of a specific APS intra-articular injection (nSTRIDE) on patient-reported outcome measures compared to saline in moderate knee OA. Methods. A parallel, double-blinded, placebo-controlled randomized controlled trial was conducted, where patients with unilateral moderate knee OA (Kellgren-Lawrence grade 2 or 3) received either nSTRIDE or saline (placebo) injection to their symptomatic knee. The primary outcome was the difference in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score at 12 months post-intervention. Secondary outcomes included WOMAC component scores, Knee injury and Osteoarthritis Outcome Score (KOOS), and visual analogue scale (VAS) scores at all follow-up timepoints (three, six, and 12 months). Results. A total of 40 patients were analyzed (21 nSTRIDE; 19 saline) in the study. No significant difference was found between nSTRIDE and saline groups for WOMAC total score at 12 months (mean difference -10.4 (95% CI -24.4 to 3.6; p = 0.141). There were no significant differences in WOMAC or KOOS scores across all timepoints. VAS scores favoured the saline group for both rest and worst pain scales at 12 months post-injection (mean difference (worst) 12 months 21.5 (95% CI 6.2 to 36.8; p = 0.008); mean difference (rest) 12 months 17.8 (95% CI 2.2 to 33.4; p = 0.026)). There were no adverse events recorded in either study group. Conclusion. Our study demonstrates no significant differences between nSTRIDE and saline groups in KOOS and WOMAC scores over time. Notably, APS injection resulted in significantly worse pain symptoms at 12 months compared to saline injection. Cite this article: Bone Joint J 2024;106-B(9):907–915

Aims. Meniscal allograft transplantation (MAT) for patients with symptomatic meniscal loss has demonstrated good clinical results and survivorship. Factors that affect both functional outcome and survivorship have been reported in the literature. These are typically single-centre case series with relatively small numbers and conflicting results. Our aim was to describe an international, two-centre case series, and identify factors that affect both functional outcome and survival. Methods. We report factors that affect outcome on 526 patients undergoing MAT across two sites (one in the UK and one in Italy). Outcomes of interest were the Knee injury and Osteoarthritis Outcome Score four (KOOS4) at two years and failure rates. We performed multiple regression analysis to examine for factors affecting KOOS, and Cox proportional hazards models for survivorship. Results. Our results indicate that baseline KOOS4 score affects functional outcome at two years, but no other included factors were significantly related to functional outcome. The only factor that affected failure rate was the presence of cartilage lesions down to bone on both the femur and tibia, decreasing the five-year survivorship from 95% (95% confidence interval (CI) 91 to 99) to 84% (95% CI 74 to 94). Conclusion. To our knowledge, this is the largest international cohort reporting on MAT. Our results indicate that factors such as age, BMI, and cartilage lesions down to bone on both the femur and tibia of the affected compartment should not present barriers to offering MAT. Baseline KOOS4 score and the presence of bone-on-bone arthritis can be used to help counsel patients regarding the expected risks and rewards of surgery. Cite this article: Bone Joint J 2022;104-B(6):657–662

Aims. Intraoperative pressure sensors allow surgeons to quantify soft-tissue balance during total knee arthroplasty (TKA). The aim of this study was to determine whether using sensors to achieve soft-tissue balance was more effective than manual balancing in improving outcomes in TKA. Methods. A multicentre randomized trial compared the outcomes of sensor balancing (SB) with manual balancing (MB) in 250 patients (285 TKAs). The primary outcome measure was the mean difference in the four Knee injury and Osteoarthritis Outcome Score subscales (ΔKOOS. 4. ) in the two groups, comparing the preoperative and two-year scores. Secondary outcomes included intraoperative balance data, additional patient-reported outcome measures (PROMs), and functional measures. Results. There was no significant difference in ΔKOOS. 4. between the two groups at two years (mean difference 0.4 points (95% confidence interval (CI) -4.6 to 5.4); p = 0.869), and multiple regression found that SB was not associated with a significant ΔKOOS. 4. (0.2-point increase (95% CI -5.1 to 4.6); p = 0.924). There were no significant differences between groups in other PROMs. Six-minute walking distance was significantly increased in the SB group (mean difference 29 metres; p = 0.015). Four-times as many TKAs were unbalanced in the MB group (36.8% MB vs 9.4% SB; p < 0.001). Irrespective of group assignment, no differences were found in any PROM when increasing ICPD thresholds defined balance. Conclusion. Despite improved quantitative soft-tissue balance, the use of sensors intraoperatively did not differentially improve the clinical or functional outcomes two years after TKA. These results question whether a more precisely balanced TKA that is guided by sensor data, and often achieved by more balancing interventions, will ultimately have a significant effect on clinical outcomes. Cite this article: Bone Joint J 2022;104-B(5):604–612

Aims. Knee arthroplasty surgery is a highly effective treatment for arthritis and disorders of the knee. There are a wide variety of implant brands and types of knee arthroplasty available to surgeons. As a result of a number of highly publicized failures, arthroplasty surgery is highly regulated in the UK and many other countries through national registries, introduced to monitor implant performance, surgeons, and hospitals. With time, the options available within many brand portfolios have grown, with alternative tibial or femoral components, tibial insert materials, or shapes and patella resurfacings. In this study we have investigated the effect of the expansion of implant brand portfolios and where there may be a lack of transparency around a brand name. We also aimed to establish the potential numbers of compatible implant construct combinations. Methods. Hypothetical implant brand portfolios were proposed, and the number of compatible implant construct combinations was calculated. Results. A simple knee portfolio with cemented cruciate-retaining (CR) and posterior-stabilized (PS) components, with and without a patella, has four combinations. If there are two options available for each component, the numbers double for each option, resulting in 32 combinations. The effect of adding a third option multiplies the number by 1.3. Introducing compatible uncemented options, with the effect of hybrids, multiplies the number by 4. An implant portfolio with two femoral components (both in CR and PS), with two insert options and a patella, all in cemented and uncemented versions leads to 192 possible compatible implant construct combinations. There are implant brands available to surgeons with many more than two options. Conclusion. This study demonstrates that the addition of multiple variants within a knee brand portfolio leads to a large number (many hundreds) of compatible implant construct combinations. Revision rates of implant combinations are not currently reviewed at this level of granularity, leading to the risk of camouflage of true outcomes. Cite this article: Bone Joint J 2021;103-B(10):1555–1560

Aims. Although total knee arthroplasty (TKA) is a highly successful procedure, about 20% of patients remain dissatisfied postoperatively. This proportion is derived from dichotomous models of the assessment of surgical success or failure, which may not reflect the spectrum of outcomes. The aim of this study was to explore differing responses to surgery, and assess whether there are distinct groups of patients with differing patterns of outcome. Methods. This was a secondary analysis of a UK multicentre TKA longitudinal cohort study. We used a group-based trajectory modelling analysis of Oxford Knee Score (OKS) in the first year following surgery with longitudinal data involving five different timepoints and multiple predictor variables. Associations between the derived trajectory groups and categorical baseline variables were assessed, and predictors of trajectory group membership were identified using Poisson regression and multinomial logistic regression, as appropriate. The final model was adjusted for sociodemographic factors (age, sex) and baseline OKS. Results. Data from 731 patients were available for analysis. Three distinct trajectories of outcome were identified: “poor” 14.0%, “modest” 39.1%, and “good” 46.9%. The predicted probability of membership for patients assigned to each trajectory group was high (0.89 to 0.93). Preoperative mental, physical health, and psychosocial factors determined which trajectory is likely to be followed. Poor responders were characterized by a comparatively small number of factors, preoperative expectations of pain and limitations, coping strategies, and a lower baseline physical health status, while the good responders were characterized by a combination of clinical, psychosocial, mental health, and quality of life factors. Conclusion. We identified three distinct response trajectories in patients undergoing TKA. Controlling for baseline score, age, and sex, psychosocial factors such as expectations of pain and limited function and poor coping strategies differentiated the trajectory groups, suggesting a role for preoperative psychosocial support in optimizing the clinical outcome. Cite this article: Bone Joint J 2021;103-B(6):1096–1102

Aims. Social determinants of health (SDOHs) may contribute to the total cost of care (TCOC) for patients undergoing total knee arthroplasty (TKA). The aim of this study was to investigate the association between demographic data, health status, and SDOHs on 30-day length of stay (LOS) and TCOC after this procedure. Methods. Patients who underwent TKA between 1 January 2018 and 31 December 2019 were identified. A total of 234 patients with complete SDOH data were included. Data were drawn from the Chesapeake Regional Information System, the Centers for Disease Control social vulnerability index (SVI), the US Department of Agriculture, and institutional electronic medical records. The SVI identifies areas vulnerable to catastrophic events with four themed scores: socioeconomic status; household composition and disability; minority status and language; and housing and transportation. Food deserts were defined as neighbourhoods located one or ten miles from a grocery store in urban and rural areas, respectively. Multiple regression analyses were performed to determine associations with LOS and costs after controlling for various demographic parameters. Results. Divorced status was significantly associated with an increased LOS (p = 0.043). Comorbidities significantly associated with an increased LOS included chronic obstructive pulmonary disease/asthma and congestive heart failure (p = 0.043 and p = 0.001, respectively). Communities with a higher density of tobacco stores were significantly associated with an increased LOS (p = 0.017). Comorbidities significantly associated with an increased TCOC included chronic obstructive pulmonary disease (p = 0.004), dementia (p = 0.048), and heart failure (p = 0.007). Increased TCOCs were significantly associated with patients who lived in food deserts (p = 0.001) and in areas with an increased density of tobacco stores (p = 0.023). Conclusion. Divorced marital status was significantly associated with an increased LOS following TKA. Living in food deserts and in communities with more tobacco stores were significant risk factors for increased LOS and TCOC. Food access and ease of acquiring tobacco may both prove to be prognostic of outcome after TKA and an opportunity for intervention. Cite this article: Bone Joint J 2021;103-B(6 Supple A):113–118

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The aim of this study was to assess factors associated with the estimated lifetime risk of revision surgery after primary knee arthroplasty (KA).

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The optimal bearing surface design for medial unicompartmental knee arthroplasty (UKA) remains controversial. The aim of this study was to compare outcomes of fixed-bearing (FB) and mobile-bearing (MB) UKAs from a single high-volume institution.

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This systematic review and meta-analysis aimed to compare the influence of patellar resurfacing following cruciate-retaining (CR) and posterior-stabilized (PS) total knee arthroplasty (TKA) on the incidence of anterior knee pain, knee-specific patient-reported outcome measures, complication rates, and reoperation rates.

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To investigate the impact of consecutive perioperative care transitions on in-hospital recovery of patients who had primary total knee arthroplasty (TKA) over an 11-year period.

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The aim of this study was to describe the prevalence and patterns of neuropathic pain over one year in a cohort of patients with chronic post-surgical pain at three months following total knee arthroplasty (TKA).

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The Coronal Plane Alignment of the Knee (CPAK) classification has been developed to predict individual variations in inherent knee alignment. The impact of preoperative and postoperative CPAK classification phenotype on the postoperative clinical outcomes of total knee arthroplasty (TKA) remains elusive. This study aimed to examine the effect of postoperative CPAK classification phenotypes (I to IX), and their pre- to postoperative changes on patient-reported outcome measures (PROMs).

Aims. The purpose of this investigation was to determine the relationship between height, weight, and sex with implant size in total knee arthroplasty (TKA) using a multivariate linear regression model and a Bayesian model. Methods. A retrospective review of an institutional registry was performed of primary TKAs performed between January 2005 and December 2016. Patient demographics including patient age, sex, height, weight, and body mass index (BMI) were obtained from registry and medical record review. In total, 8,100 primary TKAs were included. The mean age was 67.3 years (SD 9.5) with a mean BMI of 30.4 kg/m. 2. (SD 6.3). The TKAs were randomly split into a training cohort (n = 4,022) and a testing cohort (n = 4,078). A multivariate linear regression model was created on the training cohort and then applied to the testing cohort . A Bayesian model was created based on the frequencies of implant sizes in the training cohort. The model was then applied to the testing cohort to determine the accuracy of the model at 1%, 5%, and 10% tolerance of inaccuracy. Results. Height had a relatively strong correlation with implant size (femoral component anteroposterior (AP) Pearson correlation coefficient (ρ) = 0.73, p < 0.001; tibial component mediolateral (ML) ρ = 0.77, p < 0.001). Weight had a moderately strong correlation with implant size, (femoral component AP ρ = 0.46, p < 0.001; tibial ML ρ = 0.48, p < 0.001). There was a significant linear correlation with height, weight, and sex with implant size (femoral component R. 2. = 0.607, p < 0.001; tibial R. 2. = 0.695, p < 0.001). The Bayesian model showed high accuracy in predicting the range of required implant sizes (94.4% for the femur and 96.6% for the tibia) accepting a 5% risk of inaccuracy. Conclusion. Implant size was correlated with basic demographic variables including height, weight, and sex. The linear regression and Bayesian models accurately predicted required implant sizes across multiple manufacturers based on height, weight, and sex alone. These types of predictive models may help improve operating room and implant supply chain efficiency. Level of Evidence: Level IV. Cite this article: Bone Joint J 2020;102-B(6 Supple A):85–90

Aims. While patients with psychological distress have poorer short-term outcomes after total knee arthroplasty (TKA), their longer-term function is unknown. We aimed to 1) assess the influence of preoperative mental health status on long-term functional outcomes, quality of life, and patient satisfaction; and 2) analyze the change in mental health after TKA, in a cohort of patients with no history of mental health disorder, with a minimum of ten years’ follow-up. Methods. Prospectively collected data of 122 patients undergoing primary unilateral TKA in 2006 were reviewed. Patients were assessed pre- and postoperatively at two and ten years using the Knee Society Knee Score (KSKS) and Function Score (KSFS); Oxford Knee Score (OKS); and the Mental (MCS) and Physical Component Summary (PCS) which were derived from the 36-Item Short-Form Health Survey questionnaire (SF-36). Patients were stratified into those with psychological distress (MCS < 50, n = 51) and those without (MCS ≥ 50, n = 71). Multiple regression was used to control for age, sex, BMI, Charlson Comorbidity Index (CCI), and baseline scores. The rate of expectation fulfilment and satisfaction was compared between patients with low and high MCS. Results. There was no difference in the mean KSKS, KSFS, OKS, and SF-36 PCS at two years or ten years after TKA. Equal proportions of patients in each group attained the minimal clinically important difference for each score. Psychologically distressed patients had a comparable rate of satisfaction (91.8% (47/51) vs 97.1% (69/71); p = 0.193) and fulfilment of expectations (89.8% vs 97.1%; p = 0.094). The proportion of distressed patients declined from 41.8% preoperatively to 29.8% at final follow-up (p = 0.021), and their mean SF-36 MCS improved by 10.4 points (p < 0.001). Conclusion. Patients with poor mental health undergoing TKA may experience long-term improvements in function and quality of life that are comparable to those experienced by their non-distressed counterparts. These patients also achieved a similar rate of satisfaction and expectation fulfilment. Undergoing TKA was associated with improvements in mental health in distressed patients, although this effect may be due to residual confounding. Cite this article: Bone Joint J 2020;102-B(7):845–851

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In cases of severe periprosthetic joint infection (PJI) of the knee, salvage procedures such as knee arthrodesis (KA) or above-knee amputation (AKA) must be considered. As both treatments result in limitations in quality of life (QoL), we aimed to compare outcomes and factors influencing complication rates, mortality, and mobility.