Background. The economic crisis has significantly altered the quality of life in Greece. The obvious negative impact on the offered social and health services has been adequately analysed. We aimed to determine whether the economic crisis has influenced the quantity and quality of Orthopaedic research in Greece, as mirrored from the papers presented at the annual meetings of Hellenic Association of Orthopaedic Surgery between the years 2008–2014. Methods. The abstracts of the papers (oral and posters) presented in these meetings have been examined. Details regarding the department of origin were registered. We determined the level of evidence (according to the AAOS classification system), found the amount of papers that were published in PubMed journal and noted if a department of another country participated. Results. Through the years 2008–2014 the papers concerning clinical and basic orthopaedic research that were presented were 146, 207, 304, 331, 318, 234 and 191 respectively. The percentage of those that were level 1 studies was approximately 2%, 3%, 2%, 3%, 2%, 4% and 4% respectively. The percentage of level 2 studies was 2%, 1%, 2%, 3%, 1%, 3% and 0%. Level 3 studies were the 10%, 9%, 7%, 7%, 7%, 9% and 6%. The percentage of level 4 studies was 75%, 74%, 60%, 59%, 61%, 65% and 64%. Level 5 studies were the 10%, 17%, 31%, 27%, 28%, 19% and 26%. Each year, the papers that were published in PubMed were 7%, 21%, 13%, 7%, 6%, 6% and 9%. A department of another country participated in 18%, 17%, 18%, 16%, 16%, 21% and 13% of the total of papers. Conclusion. As the economic crisis deepens, the quantity of the presented papers has been reduced. More importantly, the percentage of level 1 and 2 studies has been remained steadily low. Also, we could remark a reduction on the published studies in PubMed journals. These results raise concerns about the potential impact of the crisis in the future. Level of Evidence. IV

Robust evidence on the effectiveness of peri-operative local anaesthetic infiltration (LAI) is required before it is incorporated into the pain management regimen for patients receiving total hip replacement (THR). We assessed the effectiveness of LAI using a systematic review and a fully powered randomised controlled trial (RCT) with economic evaluation. We searched MEDLINE, Embase and Cochrane databases for RCTs of peri-operative LAI in patients receiving THR. Two reviewers screened abstracts, extracted data, and liaised with authors. Outcomes were pain, opioid use, mobilisation, hospital stay and complications. If feasible, we conducted meta-analysis. In the APEX RCT, we randomised 322 patients awaiting THR to receive additional peri-operative LAI (60mls 0.25% bupivacaine plus adrenaline) or standard anaesthesia alone. Post-operatively, all patients received patient-controlled morphine. The primary outcome was joint pain severity (WOMAC-Pain) at 12 months. Patients and outcome assessors were blinded to allocation. Within APEX, cost-effectiveness was assessed from the health and social-care perspective in relation to quality adjusted life years (QALYs) and WOMAC-Pain at 12-months. Resource use was collected from hospital records and patient questionnaires. In the systematic review, we identified 13 studies (909 patients). Patients undergoing THR receiving LAI experienced greater pain reduction at 24 hours at rest, standardised mean difference (SMD) −0.61 (95%CI −1.05, −0.16; p=0.008) and at 48 hours during activity, SMD −0.43 (95%CI −0.78, −0.09; p=0.014). Patients receiving LAI spent fewer days in hospital, used less opioids and mobilised earlier. Complications were similar between groups. Long-term outcomes were not a focus of these studies. In the APEX RCT, pain levels in hospital were broadly similar between groups, probably due to patient-controlled analgesia. Opioid use was similar between groups. Time to mobilisation and discharge were largely dependent on local protocols and did not differ between groups. Patients receiving LAI were less likely to report severe pain at 12 months than those receiving standard care, odds ratio 10.2 (95%CI 2.1, 49.6; p=0.004). Complications were similar between groups. In the economic evaluation, LAI was associated with lower costs and greater cost-effectiveness than standard care. Using a £20,000 per QALY threshold, the incremental net monetary benefit was £1,125 (95%CI £183, £2,067) and the probability of being cost-effective was greater than 98 %. The evidence suggests that peri-operative LAI is a cost-effective intervention for reducing acute and chronic post-surgical pain after THR

Robust evidence on the effectiveness of peri-operative local anaesthetic infiltration (LAI) is required before it is incorporated into the pain management regimen for patients receiving total knee replacement (TKR). To assess the effectiveness of peri-operative LAI for pain management in patients receiving TKR we conducted a systematic review, fully powered randomised controlled trial (RCT) and economic evaluation. We searched MEDLINE, Embase and Cochrane databases for RCTs of peri-operative LAI in patients receiving TKR. Two reviewers screened abstracts and extracted data. Outcomes were pain, opioid use, mobilisation, hospital stay and complications. Authors were contacted if required. When feasible, we conducted meta-analysis with studies analysed separately if a femoral nerve block (FNB) was provided. In the APEX RCT, we randomised 316 patients awaiting TKR to standard anaesthesia which included FNB, or to the same regimen with additional peri-operative LAI (60mls 0.25% bupivacaine plus adrenaline). Post-operatively, all patients received patient-controlled morphine. The primary outcome was joint pain severity (WOMAC-Pain) at 12 months. Patients and outcome assessors were blinded to allocation. Within APEX, cost-effectiveness was assessed from the health and social-care perspective in relation to quality adjusted life years (QALYs) and WOMAC-Pain at 12-months. Resource use was collected from hospital records and patient questionnaires. In the systematic review, 23 studies including 1,439 patients were identified. Compared with patients receiving no intervention, LAI reduced WOMAC-Pain by standardised mean difference (SMD) −0.40 (95%CI −0.58, −0.22; p<0.001) at 24 hours at rest and by SMD −0.27 (95%CI −0.50, −0.05; p=0.018) at 48 hours during activity. In three studies there was no difference in pain at any time point between randomised groups where all patients received FNB. Patients receiving LAI spent fewer days in hospital, used less opioids and mobilised earlier. Complications were similar between groups. Few studies reported long-term outcomes. In the APEX RCT, pain levels in hospital were broadly similar between groups. Overall opioid use was similar between groups. Time to mobilisation and discharge were largely dependent on local protocols and did not differ between groups. There were no differences in pain outcomes between groups at 12 months. In the economic evaluation, LAI was marginally associated with lower costs. Using the NICE £20,000 per QALY threshold, the incremental net monetary benefit was £264 (95%CI, −£710, £1,238) and the probability of being cost-effective was 62%. Although LAI appeared to have some benefit for reduced pain in hospital after TKR there was no evidence of pain control additional to that provided by femoral nerve block, however it would be cost-effective at the current NICE thresholds

Open lower limb fractures are resource-intensive fractures, accounting for a significant proportion of the workload and cost of orthopaedic trauma units. A recent study has evaluated that the median cost of direct inpatient treatment of open lower-limb fractures in the National Health Service (NHS) is steep, at £19189 per patient. Healthcare providers are expected to be aware of the costs of treatments, although there is very limited dissemination of this information, neither on a national or local level. Older adults (>65 years old) are at an increased risk of the types of high-energy injuries that can result in open lower limb fractures. Generally, there remains a significant lack of literature surrounding the cost of open fracture management, especially in specific patient groups that are disproportionately affected by these fractures. This study has calculated the direct inpatient care costs of older adults with open lower limb fractures.

Open lower limb fractures in adult patients over 65 years old treated at Addenbrooke's Hospital of Cambridge University Hospitals NHS Trust were identified over the period of March 2014-March 2019. Isolated fractures of the femur, tibia and fibula over this time period were included. Direct inpatient care costs were calculated using information about the sustained fracture, operative time, implant(s) and theatre kit(s) used, the number of patient bed-days on the orthopaedic ward and critical care unit, and the number of hours of inpatient physiotherapy received. Direct inpatient care costs were compared with the income received by our centre for each of these cases, according to Healthcare Resource Group (HRG) cost codes. Our data was also compared with existing literature on Patient Level Costing (PLC) figures for open lower limb fractures.

We extracted data from 58 patients over the age of 65 years treated for open isolated lower limb fractures at Addenbrooke's Hospital, Cambridge University Hospitals NHS Trust, between March 2014 and March 2019. The median cost of inpatient care calculated in this study was £20,398 per patient, resulting in a financial loss to the hospital of £5113 per patient. When the results were disaggregated by sex, the median cost for an open lower limb fracture in a male patient was £20,886 compared to £19,304 in a female patient. Data were also disaggregated by the site of injury, which produced a median cost for an open femur fracture of £23,949, and £24,549 and £15,362 for open tibia and ankle fractures, respectively.

The absence of published primary literature and clinical audits on this topic continues to hinder the inclusion of cost-effectiveness as an important factor in clinical decision-making. This study provides valuable insight into the true cost of open lower limb fractures in a key patient population in a Major Trauma Centre in England and highlights the large losses incurred by hospitals in treating these cases. These results support the revision of the remuneration structures in the NHS for the treatment of elderly patients with these injuries.

Summary Statement. Using current analysis/methodology, new implant technology is unlikely to demonstrate a large enough change in patient function to impact on the cost-effectiveness of the procedure. Purpose. Cost effectiveness is an increasingly important metric in today's healthcare environment, and decisions surrounding which arthroplasty prosthesis to implant are not exempt from such health economic concerns. Quality adjusted life years (QALYs) are the typical assessment tool for this type of evaluation. Using this methodology, joint arthroplasty has been shown to be cost effective, however studies directly comparing the QALY achieved by differing prostheses are lacking. Methods. Data was gathered in a single centre prospective double-blind randomised controlled trial comparing the outcome a modern implant, the Triathlon total knee replacement, with its traditionally designed predecessor the Kinemax, using the Short Form 6 dimensional (SF-6D) score and quality adjusted life year (QALY) methodology. The study cohort consisted of 64 patients that were randomised to a Triathlon and 60 randomised to a Kinemax. Results. There was a significant improvement in the SF-6D score for both groups at one year compared with pre-operative scores (p<0.0001). The calculated overall life expectancy for the study cohort was 15.1 years, which resulted in an overall QALY gain of 2.144 (95% CI 1.752–2.507). The modern implant group demonstrated only a small improvement in the SF-6D score compared to the traditional design at one year (0.141 versus 0.143, p=0.94). This difference in health gain resulted in the modern implant costing £298 less per QALY at one year, however this saving diminished to less than £30 per year over the lifetime of the cohort. Discussion. This study demonstrates that despite comparing 2nd and 4th generation design, modern implant technology does not influence the cost-effectiveness of TKA using the SF-6D and QALY methodology. As most implants demonstrate similar longevity, differences in patient function will likely carry the greatest influence on QALY. This type of analysis however assesses health status, and is not sensitive to joint specific function. Dramatic differences in patient outcome would be required to influence QALY score. Evolutionary design changes in implant technology are thus unlikely to influence QALY analysis following joint replacement, which has important implication for implant procurement

Background. One untested back pain treatment model is to stratify management depending on prognosis (low, medium or high-risk). This 2-arm RCT investigated: (i) overall clinical and cost-effectiveness of stratified primary care (intervention), versus non-stratified current best practice (control); and (ii) whether low-risk patients had non-inferior outcomes, and medium/high-risk groups had superior outcomes. Methods. 1573 adults with back pain (+/− radiculopathy) consulting at 10 general practices in England responded to invitations to attend an assessment clinic, at which 851 eligible participants were randomised (intervention n=568; control n=283). Primary outcome using intention-to-treat analysis was the difference in change in the Roland-Morris Disability Questionnaire (RMDQ) score at 12 months. Secondary outcomes included 4-month RMDQ change between arms overall, and at risk-group level at both time-points. The economic evaluation estimated incremental quality-adjusted life years (QALYs) and back pain-related health care costs. Results. Overall, between-group differences in RMDQ adjusted mean change scores significantly favoured stratified care; 1·8 (95%CI 1·1, 2·6) at 4-months and 1·1 (95%CI 0·3, 1·9) at 12-months. Stratified care was associated with an increase in generic health benefit (0.039 additional QALYs) and cost savings. Low-risk patients had non-inferior outcomes compared with controls, and there were significant between-group differences in RMDQ adjusted mean change scores for medium-risk patients at 4 (1·99 [95%CI 0·75, 3·22]) and 12 months (1·33 [95%CI 0·15, 2·52]), and high-risk patients at 4 months (2·53 [95%CI 0·90, 4·16]). Conclusion. A stratified approach of prognostic screening with treatment matched pathways for patients in primary care with back pain provides significant improvements in clinical and economic outcomes compared to current best practice. Conflicts of Interest. None. Source of Funding. Arthritis Research UK. This abstract has been presented at 3 international conferences but not yet at a national conference. It has also been accepted for publication in the Lancet – but is not yet published

Introduction:

Mayo 2A Olecranon fractures are traditionally managed with a tension band wire device (TBW) but locking plates may also be used to treat these injuries.

Infections are among the most diffused complications of the implantation of medical devices. In orthopedics, they pose severe societal and economic burden and interfere with the capability of the implants to integrate in the host bone, significantly increasing failure risk. Infection is particularly severe in the case of comorbidities and especially bone tumors, since oncologic patients are fragile, have higher infection rate and impaired osteoregenerative capabilities. For this reason, prevention of infection is to be preferred over treatment. This is even more important in the case of spine surgery, since spine is among the main site for tumor metastases and because incidence of post operative surgical-site infections is significant (up to 15-20%) and surgical options are limited by the need of avoiding damaging the spinal cord. Functionalization of the implant surfaces, so as to address infection and, possibly, co- adjuvate anti-tumor treatments, appears as a breakthrough innovation. Unmet clinical needs in infection and tumors is presented, with a specific focus on the spine, then, new perspectives are highlighted for their treatment

Osteoarthritis (OA), the most prevalent chronic joint disease, represents a relevant social and economic burden worldwide. Human umbilical cord mesenchymal stem cells (HUCMSCs) have been used for injection into the joint cavity to treat OA. The aim of this article is to clarify whether Huc-MSCs derived exosomes could inhibit the progression of OA and the mechanism in this process. A rabbit OA model was established by the transection of the anterior cruciate ligament. The effects of HUCMSCs or exosomes derived from HUCMSCs on repairing articular cartilage of knee osteoarthritis was examined by micro-CT. Immunohistochemical experiments were used to confirm the expression of relevant inflammatory molecules in OA. In vitro experiments, Transwell assay was used to assess the migration of macrophages induced by TNF-a. Results showed that a large number of macrophages migrated in arthcular cavity in OA model in vivo, while local injection of HUCMSCs and exosomes did repair the articular cartilage. Immunohistochemical results suggested that the expression of CCL2 and CD68 in the OA rabbit model increased significantly, but was significantly reduced by HUCMSCs or exosomes. Transwell assay showed that both HUCMSCs and exosomes can effectively inhibit the migration of macrophage. In conclusion, the exosomes derived by HUCMSCs might might rescue cartilage defects in rabbit through its anti-inflammatory effects through inhibiting CCL2

Traumatic acute or chronic tendon injuries are a wide clinical problem in modern society, resulting in important economic burden to the health system and poor quality of life in patients. Due to the low cellularity and vascularity of tendon tissue the repair process is slow and inefficient, resulting in mechanically, structurally, and functionally inferior tissue. Tissue engineering and regenerative medicine are promising alternatives to the natural healing process for tendon repair, especially in the reconstruction of large damaged tissues. The aim of TRITONE project is to develop a smart, bioactive implantable 3D printed scaffold, able to reproduce the structural and functional properties of human tendon, using FDA approved materials and starting from MSC and their precursor, MPC cell mixtures from human donors. Total cohort selected in the last 12 months was divided in group 1 (N=20) of subjects with tendon injury and group 2 (N=20) of healthy subject. Groups were profiled and age and gender matched. Inclusion criteria were age>18 years and presence of informed consent. Ongoing pregnancy, antihypertensive treatment, cardiovascular diseases, ongoing treatment with anti-aggregants, acetylsalicylic-acid or lithium and age<18 years were exclusion criteria. Firstly, we defined clinical, biological, nutritional life style and genetic profile of the cohort. The deficiency of certain nutrients and sex hormonal differences were correlated with tendon-injured patients. It was established the optimal amount of MPC/MSC human cell (collected from different patients during femoral neck osteotomy). Finally, most suitable biomaterials for tendon regeneration and polymer tendon-like structure were identified. Hyaluronic acid, chemical surface and soft-molecular imprinting (SOFT-MI) was used to functionalize the scaffold. These preliminary results are promising. It will be necessary to enroll many more patients to identify genetic status connected with the onset of tendinopathy. The functional and structural characterization of smart bioactive tendon in dynamic environment will represent the next project step

Abstract. Objectives. Spinal disorders such as back pain incur a substantial societal and economic burden. Unfortunately, there is lack of understanding and treatment of these disorders are further impeded by the inability to assess spinal forces in vivo. The aim of this project is to address this challenge by developing and testing a novel image-driven approach that will assess the forces in an individual's spine in vivo by incorporating information acquired from multimodal imaging (magnetic resonance imaging (MRI) and biplane X-rays) in a subject-specific model. Methods. Magnetic resonance and biplane X-ray imaging are used to capture information about the anatomy, tissues, and motion of an individual's spine as they perform a range of everyday activities. This information is then utilised in a subject-specific computational model based on the finite element method to predict the forces in their spine. The project is also utilising novel machine learning algorithms and in vitro, six-axis mechanical testing on human, porcine and bovine samples to develop and test the modelling methods rigorously. Results & Discussion. MRI sequences have been identified that provide high-quality image data and information on different tissue types which will be used to predict subject-specific disc properties. In-vivo protocols to capture motion analysis, EMG muscle activity, and video X-rays of the spine have been designed with planned data collection of 15 healthy volunteers. Preliminary modelling work has evaluated potential machine learning approaches and quantified the sensitivity of the models developed to material properties. Conclusion. The development and testing of these image-driven subject-specific spine models will provide a new tool for determining forces in the spine. It will also provide new tools for measuring and modelling spine movement and quantifying the properties of the spinal tissues. Acknowledgments. Funding from the EPSRC: EP/V036602/1 (Meakin, Holsgrove & Javadi) and EP/V032275/1 (Holt & Williams). Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Reduction of length of stay (LOS) without compromising quality of care is a trend observed in orthopaedic departments. To achieve this goal the pathway needs to be optimised. This requires team work than can be supported by e-health solutions. The objective of this study was to assess the impact of reduction in LOS on complications and readmissions in one hospital where accelerated discharge was introduced due to the pandemic. 317 patients with primary total hip and total knee replacements treated in the same hospital between October 2018 and February 2021 were included. The patients were divided in two groups: the pre-pandemic group and the pandemic group. The discharge criteria were: patient feels comfortable with going back home, patient has enough support at home, no wound leakage, and independence in activities of daily living. No face-to-face surgeon or nurse follow-up was planned. Patients’ progress was monitored via the mobile application. The patients received information, education materials, postoperative exercises and a coaching via secure chat. The length of stay (LOS) and complications were assessed through questions in the app and patients filled in standard PROMs preoperatively, at 6 weeks and 3 months. Before the pandemic, 64.8% of the patients spent 3 nights at hospital, whereas during the pandemic, 52.0% spent only 1 night. The median value changed from 3 days to 1 day. The complication rate before the pandemic of 15% dropped to 9 % during the pandemic. The readmission rate remained stable with 4% before the pandemic and 5 % during the pandemic. No difference were observed for PROMS between groups. The results of this study showed that after a hip and knee surgery, the shortening of the LOS from three to one night resulted in less complications and a stable rate of readmissions. These results are in line with literature data on enhanced recovery after hip and knee arthroplasty. The reduction of LOS for elective knee and hip arthroplasty during the pandemic period proved safe. The concept used in this study is transferable to other hospitals, and may have economic implications through reduced hospital costs

Worldwide, tendon disorders are one of the main causes of disability that decrease the quality of life of individuals and represent a substantial economic burden on society. Currently, the main therapies used for tendon injuries are not able to restore tendon functionality, and due to tendons' hypovascular and hypocellular nature, they present a reduced healing capacity, which also limits the success of the available therapies. In order to discover new therapies, extracellular vesicles (EVs), key players in cell-cell communication, have been widely explored for tissue engineering and regenerative medicine applications. Thus, the aim of this study is to assess the role of EVs derived from platelets in stem cell tenogenic commitment using a bioengineered tendon in vitro model for potential use as tendon therapeutic agents. Biomimetic platelet-derived EVs were produced by freeze-thaw cycles of platelets and isolation at different centrifugation speed. To recreate the architecture of tendons, a 3D system consisting of electrospun anisotropic nanofiber scaffolds coated with collagen encapsulating human adipose stem cells (hASCs) and different types of platelet-derived EVs, were produced. Then, the influence of the tendon-mimetic constructs and the distinct EVs populations in the hASCs tenogenic differentiation were assessed over culture time. We observed that the hASCs on the nanofibrous tendon scaffolds, show high cytoskeleton anisotropic organization that is characteristic of tenocytes. Moreover, acting as biological cues, platelet-derived EVs boosted hASCs tenogenic commitment, supported by the increased gene expression of tendon-related markers (SCX and TNMD). Additionally, EVs enhanced the deposition of tendon like extracellular matrix (ECM), as evidenced by the increased gene expression of ECM-related markers such as COL1, COL3, DCN, TNC, and MMP-3, which are fundamental for ECM synthesis and degradation balance. Moreover, EVs induced lower collagen matrix contraction on hASCs, which has been related with lower myofibroblast differentiation. Overall, the results revealed that EVs are capable of modulating stem cells' behavior boosting their tenogenic commitment, through the increased expression of healthy tendon cell markers, potentiating ECM deposition and decreasing cell contractility. Therefore, platelet EVs are a promising biochemical tool, worthy to be further explored, as paracrine signaling that might potentiate tendon repair and regeneration

In current practice in the UK there are three main approaches to investigating suspected scaphoid fractures not seen on initial plain film x-rays. Early MRI of all cases. Review all cases in clinic at two weeks with repeat x-rays. Hybrid model. Virtual Fracture Clinic (VFC) triage to reduce those who are seen in clinic at two weeks by:. ∘. Organising early MRI for those with high-risk presentation. ∘. Discharging those with an alternative more likely diagnosis. Our unit uses the VFC model. We aimed to evaluate its efficiency, safety, clinical outcomes and economic viability. All patients attending the emergency department with either a confirmed or suspected scaphoid fracture between March and December 2020 were included (n=305). Of these 297 were referred to the VFC: 33 had a confirmed fracture on x-ray and 264 had a suspected fracture. Of the suspected fractures reviewed in VFC 14% had an MRI organised directly owing to a high-risk presentation, 79% were brought for fracture clinic review and 17% discharged with an alternative diagnosis such as osteoarthritis. Of those subsequently reviewed in fracture clinic at two weeks: 9% were treated as scaphoid fractures (based on clinical suspicion and repeat x-rays), 17% had MRI or CT imaging organised, 5% did not attend and 69% were discharged. Overall, 17% of cases initially triaged, had further imaging – 41 MRIs and 5 CTs. MRI detected: 5% scaphoid fracture, 17% other fracture, 24% bone contusion, complete ligament tear 10%, partial ligament tear 39% and normal study 10%. The results of MRI minimally affected management. 3 patients were taken out of plaster early, 1 patient was immobilized who was not previously and no patients underwent operative management. In the following 12-month period one patient re-presented with a hand or wrist issue. This approach avoided 218 MRIs, equating to £24000 and 109 hours of scanner time. VFC triage and selective use of MRI scanning is a safe, efficient and cost-effective method for the management suspected scaphoid fractures. This can be implemented in units without the resource to MRI all suspected scaphoid fractures from the emergency department

Is Non-Weight-Bearing Necessary? (INWN) is a pragmatic multicentre randomised controlled trial comparing immediate protected weight-bearing (IWB) with non-weight-bearing cast immobilisation (NWB) following ankle fracture fixation (ORIF). This trial compares; functional outcomes, complication rates and performs an economic analysis to estimate cost-utility. IWB within 24hrs was compared to NWB, following ORIF of all types of unstable ankle fractures. Skeletally immature patients and tibial plafond fractures were excluded. Functional outcomes were assessed by the Olerud-Molander Ankle Score (OMAS) and RAND-36 Item Short Form Survey (SF-36) taken at regular follow-up intervals up to one year. A cost-utility analysis via decision tree modelling was performed to derive an incremental cost effectiveness ratio (ICER). A standard gamble health state valuation model utilising SF-36 scores was used to calculate Quality Adjusted Life Years (QALYs) for each arm. We recruited 160 patients (80 per arm), aged 15 to 94 years (M = 45.5), 54% female. Complication rates were similar in both groups. IWB demonstrated a consistently higher OMAS score, with significant values at 6 weeks (MD=10.4, p=0.005) and 3 months (MD 12.0, p=0.003). Standard gamble utility values demonstrated consistently higher values (a score of 1 equals perfect health) with IWB, significant at 3 months (Ẋ = 0.75 [IWB] / 0.69 [NWB], p=0.018). Cost-utility analysis demonstrated NWB is €798.02 more expensive and results in 0.04 fewer QALYs over 1 year. This results in an ICER of −€21,682.42/QALY. This negative ICER indicates cost savings of €21,682.42 for every QALY (25 patients = 1 QALY gain) gained implementing an IWB regime. IWB demonstrates a superior functional outcome, greater cost savings and similar complication rates, compared to NWB following ankle fracture fixation

Even minor lesions in articular cartilage (AC) can cause underlying bone damage creating an osteochondral (OC) defect. OC defects can cause pain, impaired mobility and can develop to osteoarthritis (OA). OA is a disease that affects nearly 10% of the population worldwide. [1]. , and represents a significant economic burden to patients and society. [2]. While significant progress has been made in this field, realising an efficacious therapeutic option for unresolved OA remains elusive and is considered one of the greatest challenges in the field of orthopaedic regenerative medicine. [3]. Therefore, there is a societal need to develop new strategies for AC regeneration. In recent years there has been increased interest in the use of tissue-specific aligned porous freeze-dried extracellular matrix (ECM) scaffolds as an off-the-shelf approach for AC repair, as they allow for cell infiltration, provide biological cues to direct target-tissue repair and permit aligned tissue deposition, desired in AC repair. [4]. However, most ECM-scaffolds lack the appropriate mechanical properties to withstand the loads passing through the joint. [5]. One solution to this problem is to reinforce the ECM with a stiffer framework made of synthetic materials, such as polylactic acid (PLA). [6]. Such framework can be 3D printed to produce anatomically accurate implants. [7]. , attractive in personalized medicine. However, typical 3D prints are static, their design is not optimized for soft-hard interfaces (OC interface), and they may not adapt to the cyclic loading passing through our joints, thus risking implant failure. To tackle this limitation, more compliant or dynamic designs can be printed, such as coil-shaped structures. [8]. Thus, in this study we use finite element modelling to create different designs that mimic the mechanical properties of AC and prototype them in PLA, using polyvinyl alcohol as support. The optimal design will be combined with an ECM scaffold containing a tailored microarchitecture mimicking aspects of native AC. Acknowledgments: This project has received funding from the European Union's Horizon Europe research and innovation MSCA PF programme under grant agreement No. 101110000

Intervertebral disc degeneration (IDD) affects more than 80% of the population all over the world. Current strategies for the treatment of IDD are based on conservative or surgical procedures with the aim of relieving pain. Mesenchymal stem cell (MSC) transplantation has emerged as a promising therapy in recent decades, but studies showed that the particularly hostile microenvironment in the intervertebral disc (IVD) can compromise cells survival rate. The use of exosomes, extracellular vesicles released by various cell types, possess considerable economic advantages including low immunogenicity and toxicity. Exosomes allow intercellular communication by conveying functional proteins, RNA, miRNA and lipids between cells. The purpose of this study is to assess the therapeutic effects of exosomes derived from Wharton Jelly mesenchymal stromal cells (WJ-MSC) on human nucleuspulposus cells (hNPC) in an in vitro 3D culture model. Exosomes (exos) were isolated by tangential flow filtration of WJ-MSC conditioned media and characterized by: quantification with BCA test; morphological observation with TEM, surface marker expression by WB and size evaluation by NTA. Confocal microscopy has been used to identify exosomes marked with PKH26 and monitor fusion and/or incorporation in hNPC. hNPC were isolated from waste surgical material from patients undergoing discectomy (n = 5), expanded, encapsulated in alginate beads and treated with: culture medium (control group); WJ-MSC exos (WJ-exos) at different concentrations (10 μg/ml, 50 μg/ml and 100 μg/ml). They were then analysed for: cell proliferation (Trypan Blu); viability (Live/Dead Assay); quantification of nitrites (Griess) and glycosaminoglycans, GAG (DMBB). The hNPC in alginate beads treated for 7 days were included in paraffin and histologically analysed to determine the presence of extracellular matrix (ECM) components. Finally, the expression levels of catabolic and anabolic genes were evaluated through real-time polymerase chain reaction (qPCR). All concentrations of WJ-exos under exam were capable to induce a significant increase in cell proliferation after 10 and 14 days of treatment (p < 0.01 and p < 0.001, respectively). Live/Dead assay showed a decrease in cell death at 50 μg/ml of WJ-exos (p < 0.05). While cellular oxidative stress indicator, nitrite production, was reduced in a dose-dependent way and statistically significant only with 100 μg/ml of WJ-exos (p < 0.05). WJ-exos at 10 and 100 μg/ml induced a significant increase in GAG content (p < 0.05; p < 0.01, respectively) confirmed by Alcian Blu staining. Exos derived from WJ-MSC modulated gene expression levels by increasing expression of ACAN and SOX-9 genes and reducing significantly of IL-6, MMP-1, MMP-13 and ADAMTS-5 levels (p < 0.05; p < 0.01) compared to the control group. Our results supported the potential use of exosomes from WJ-MSC for the treatment of IDD. Exosomes improved hNPC growth, attenuated ECM degradation and reduced oxidative stress and inflammation. This study offers a new scenario in IVD regeneration, promoting the potential use of extracellular vesicles as an alternative strategy to cell therapy

Introduction and Objective. Total knee arthroplasty (TKA) is a frequently and increasingly performed surgery in the treatment of disabling knee osteoarthritis. The rising number of procedures and related revisions pose an increasing economic burden on health care systems. In an attempt to lower the revision rate due to component malalignment and soft tissue imbalance in TKA, robotic assistance (RA) has been introduced in the operating theatre. The primary objective of this study is to provide the results of a theoretical, preliminary cost-effectiveness analysis of RA TKA. Materials and Methods. A Markov state-transition model was designed to model the health status of sixty-seven-year-old patients in need of TKA due to primary osteoarthritis over a twenty-year period following their knee joint replacement. Transitional probabilities and independent variables were extracted from existing literature. Patients’ state in the transition model was able to change on an annual basis. The main differences between the conventional and RA TKA were the outlier rate in the coronal plane and the cost of the procedure. In RA TKA, it was hypothesized that there were lower revision rates due to a lower outlier rate compared to conventional TKA. Results. The value attributed to the utility both for primary and revision surgery has the biggest impact on the ICER, followed by the rate of successful primary surgery and the cost of RA-technology. Only 2.18–2.34% of the samples yielded from the probabilistic sensitivity analysis proved to be cost-effective (threshold set at $50000/QALY). A calculated surgical volume of at least 191–253 cases per robot per year is needed to prove cost-effective taking the predetermined parameter values into account. Conclusions. Robot-assisted TKA might be a cost-effective procedure compared to conventional TKA if a minimum of 191 cases are performed on a yearly basis, depending on the cost of the robot. The cost-benefit of the robotic TKA surgery is mainly based on a decreased revision rate. This study is based on the assumption that alignment is a predictor of success in total knee arthroplasty. Until there is data confirming the assertion that alignment predicts success robot-assisted surgery cannot be recommended

Background. The Arthroplasty Pain Experience (APEX) studies are two randomised controlled trials in primary total hip (THR) and knee replacement (TKR) at a large UK orthopaedics centre. APEX investigated the effect of local anaesthetic wound infiltration (LAI), administered before wound closure, in addition to standard analgesia, on pain severity at 12 months. This abstract reports results of the within-trial economic evaluations. Methods. Cost-effectiveness was assessed from the health and social care payer perspective in relation to quality adjusted life years (QALYs). Resource use was collected from hospital records and patient-completed postal questionnaires, and valued using unit cost estimates from local NHS Trust and national tariffs. Missing data were imputed using chained equations. Costs and outcomes were compared per trial arm and plotted in cost-effectiveness planes. The economic results were bootstrapped incremental net monetary benefit statistics (INMB) and cost-effectiveness acceptability curves. One-way deterministic sensitivity analyses explored any methodological uncertainty. Results. In both trials, LAI was cost-saving and more effective than standard care. Using the £20,000 per QALY threshold, in THR, the INMB was £1,125 (95%BCI, £183 to £2,067) and the probability of being cost-effective was over 98%. In TKR, the INMB was £264 (95%BCI, −£710 to £1,238), with only 62% probability of being cost-effective. Considering an NHS perspective only, LAI was no longer dominant in THR, but still highly cost-effective, with an INMB of £961 (95%BCI, £50 to £1,873). Conclusions. Administering LAI is a cost-effective treatment option in THR and TKR surgeries. The evidence is stronger for THR, because of larger QALY gain. In TKR, there is more uncertainty around the economic result, and smaller QALY gains, but results point to LAI being cheaper than standard analgesia, which includes a femoral nerve block. Trial Registration. ISRCTN96095682, 29/04/2010. Funding. NIHR Programme Grant for Applied Research RP-PG-0407-10070

Revision anterior cruciate ligament (ACL) reconstruction is a technically demanding procedure, reporting poorer outcomes compared to the primary procedure. Identification of the cause of primary failure and a thorough pre-operative evaluation is required to plan the most appropriate surgical approach. 3D printing technology has become increasingly commonplace in the surgical setting. In particular, patient-specific anatomical models can be used to aid pre-operative planning of complicated procedures. We have conducted a qualitative study to gauge the interest amongst orthopaedic knee surgeons in using a 3D-printed model to plan revision ACL reconstructions. A tibia and femur model was printed from one patient who is a candidate for the procedure. The binder jetting printing technique was performed, using Visijet PXL Core powder. 12 orthopaedic knee surgeons assessed the usefulness of the 3D-printed model compared to conventional CT images on a likert scale. 6 key steps of preoperative planning were assessed, including the size and location of the tunnel defects, the need for notchplasty, and whether a staged revision was required. We found that surgeons preferred the 3D-printed model to conventional CT images only, and 83% of them would use such a model for both pre-operative simulation, and as an intra-operative reference. However, there were some variation in the perceived usefulness of the model in several areas assessed. This may reflect differences in individual approach towards planning of the procedure. Our findings suggest that 3D-printed models could be a versatile pre-operative and intra-operative tool for complicated arthroscopic knee surgery. While 3D printing technology is becoming increasingly accessible and affordable, in-depth cost-effectiveness studies need to be conducted before it can be integrated into clinical. Further study would be needed to determine the clinical utility and economic cost-effectiveness of the 3D-printed model in revision ACL reconstruction