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Abstract Achilles tendinopathy is a disabling condition that affects more than 50% of runners. Pre-clinical studies in a large animal model of naturally-occurring tendinopathy similar to human Achilles tendinopathy has shown benefits of autologous bone marrow-derived mesenchymal stem cell (MSC) implantation. However, MSCs are advanced therapies medicinal products (ATMPs), with strict regulatory requirements. Guided by the regulator we carried out a first in man study to assess the safety and efficacy of autologous MSC injection in human patients with non-insertional Achilles tendinopathy. Ten patients, mean age 47 with mid-portion Achilles tendon pain and swelling for more than 6 months, underwent autologous cultured cell injections (median 12.2 × 106, range 5–19 × 106 cells) into their Achilles tendon. At 24 weeks follow-up, no serious adverse reactions or important medical events were observed. MOXFQ, EQ-5D-5L, and VISA-A scores improved clinically at 12 and 24 weeks. VAS pain improved increasingly at 6, 12 and 24 weeks. MOXFQ Pain and VISA-A Scores improved > 12 points from baseline to 24 weeks in 8 patients. Maximum anteroposterior tendon thickness as measured by greyscale US decreased by mean 0.8 mm at 24 weeks. This phase IIa study demonstrated the safety of autologous MSC injection for non-insertional Achilles tendinopathy and provides proof-of-concept of the technique in patients, all of whom had previously failed conservative treatments for chronic disease and leads the way for a larger randomised controlled trial.

Abstract The early effects of progressive collapsing foot deformity (PCFD) on the ankle and syndesmotic joints have not been three-dimensionally quantified. This case-control study focused on using weight bearing CT (WBCT) distance (DM) and coverage maps (CM) and volumetric measurements as 3D radiological markers to objectively characterize early effects of PCFD on the ankle and syndesmotic joints. Seventeen consecutive patients with symptomatic stage I flexible PCFD and 20 matched controls that underwent foot/ankle WBCT were included. Three-dimensional DM and CM of the ankle and syndesmotic joints, as well volumetric assessment of the distal tibiofibular syndesmosis was performed as possible WBCT markers of early PCFD. Measurements were compared between PCFD and controls. Significant overall reductions in syndesmotic incisura distances were observed in PCFD patients when compared to controls, with no difference in the overall syndesmotic incisura volume at 1, 3, 5 and 10 cm proximally to the ankle joint. CMs showed significantly decreased articular coverage of the anterior regions of the tibiotalar joint as well as medial/lateral ankle joint gutters in PCFD patients. This study showed syndesmotic narrowing and decreased articular coverage of the anterior aspect of the ankle gutters and talar dome in stage I PCFD patients when compared to controls. These findings are consistent with early plantarflexion of the talus within the ankle Mortise, and absence of true syndesmotic overload in early PCFD, and support DM and CM as early 3D PCFD radiological markers.

Category: Ankle Arthritis Introduction/Purpose: Despite the increasing numbers of ankle replacements that are being performed there are still limited studies on the survival of ankle replacements and which factors influence survivorship comparisons between different implants. The primary aim of this study is to link NJR data with NHS digital data to determine the true failure rates of ankle replacements and to determine the risk factors for failure of total ankle replacements Methods: A data linkage study combined National Joint Registry Data and NHS Digital data. The primary outcome of failure is defined as the removal or exchange of any components of the implanted device inserted during ankle replacement surgery. Life tables and Kaplan Meier survival charts demonstrated survivorship. Cox proportional hazards regression models with the Breslow method used for ties were fitted to compare failure rates. Results: 5,562 primary ankle replacement were recorded on the NJR between 1st April 2010 and 31st December 2018. The unadjusted 1-year survivorship of ankle replacements was 98.8% (95% CI 98.4%-99.0the 5-year survival in 2725 patients was 90.2% (95% CI 89.2%-91.1) and the 10-year survival in 199 patients was 86.2% (95% CI 84.6%-87.6%). In univariate cox regression models age, BMI, ASA, Charlson co-morbidity score, indication for surgery were significantly associated with an increased risk of failure. In multivariate cox regression models only age (HR 0.956, 95% CI 0.942-0.970), BMI (HR 1.032, 95% CI 1.006-1.059) and indication (HR 0.880, 95% CI 0.799-0.968) were associated with an increased risk of failure. Conclusion: Ankle replacements have been demonstrated to have higher failure rates in younger patients, those with an increased BMI, and those with osteoarthritis. These findings should be taken into account when deciding which patients should undergo an ankle replacement and in counselling them on the likely survivorship of their ankle replacement

Category: Ankle Arthritis Introduction/Purpose: Total talus replacements have been proposed as a method to treat talar AVN replacing the entire talus. The potential for total talar replacements has increased with the advent of patient specific implants utilising 3D printing based on CT scanning of the ipsilateral or contralateral talus. The primary aim of this systematic review is to analyse the current literature on total talus replacements. It specifically aims to look at the indications, complications, survival and functional outcomes. Methods: A systematic review was undertaken including all levels of evidence and following PRISMA guidelines. Basic percentages and a weighted pooled proportion for failures using the Freeman Tukey double arscine transformation were performed. Results: 9 papers with 151 patients were included. The mean age ranged from 27.6 to 72, with 5 papers having a mean age of less than 50. Mean follow-up ranged from 12.8 to 58 months. The most common indication was avascular necrosis in 103 patients.4 studies used 3D printing and 5 customised implants. 3 studies undertook a talus replacement with an ankle replacement. 4 studies used ceramic prostheses, 3 cobalt chromium 1 stainless steel and 1 titanium with ceramic surface. Post-operative complications ranged from 0 to 33%. 69.6% of 23 functional outcomes scores demonstrated significant improvement in functional scores with the others demonstrating a non-significant improvement.3 of 151 implants failed requiring further surgery with 2 revisions and 1 amputation. 6 of the 8 studies did not report any operations for failure. The cumulative incidence of failure was 0.1 % (95% CI 0.0- 4.9%). Conclusion: Total talus replacements are a potential alternative to tibiotalocalcaneal fusion for patients with avascular necrosis of the talus. Further studies are required to ensure good outcomes prior to an increase in use of this prosthesis.

Category: Ankle Arthritis Introduction/Purpose: There are limited studies on the outcomes of conversion to fusion following a failed ankle replacement. The primary aim of this NJR data linkage study is to determine the outcomes of conversion to fusion following a failed ankle replacement. Methods: A data linkage study combined National Joint Registry Data and NHS Digital data. The primary outcome of failure is defined as a further fusion procedure or amputation. Life tables and Kaplan Meier survival charts demonstrated survivorship. Cox proportional hazards regression models with the Breslow method used for ties were fitted to compare failure rates. Results: 131 patients underwent conversion to fusion. The mean time from primary replacement was 33.8 months (range 1-100). The mean age was 63.3 (range 33-85), there were 73 males (55.7%). The mean BMI was 30.7 (SD 5.3) mean ASA was 2.0 and the mean Charlson co-morbidity score was 2.5. The most commonly revised implant was the Mobility in 45.0%, Zenith in 16.8% and Box in 11.5%.105 (80.2%) were as a single stage and 26 (19.8%) as a 2 stage procedure. The 1 year survivorship was 96.0% (95% CI 90.6%-98.3%), 2 year survivorship was 83.8% (95% CI 75.4%-89.5%) and 5 year survivorship was 72.4% (95% CI 62.0%-80.4%) A Cox regression model adjusting for individual factors did not find any risk factor significantly increased the risk of failure. Conclusion: Conversion to fusion following a failed ankle replacement has high rates of further surgery. Further prospective studies are required to determine risk factors for failure to improve outcomes for these patients.

Category: Ankle Arthritis; Ankle; Hindfoot; Other Introduction/Purpose: End-stage ankle osteoarthritis (EOA) causes severe pain and chronic disability. Once non operative measures have been exhausted the two main surgical treatments include total ankle replacement (TAR) and ankle fusion (AF). Systematic reviews have confirmed that both procedures are effective but there has never been a robust randomised multicentre level I study comparing the two treatments. Our objective was to investigate and compare the clinical and cost effectiveness of TAR against AF in the treatment of end-stage ankle osteoarthritis in patients aged 50-85 years. Methods: TARVA is a multi-centre, parallel-group, open label randomised trial. Patients with EOA, aged 50-85, suitable for either procedure were recruited at 17 UK hospitals. Randomisation was carried out using a secure on-line service and was stratified by surgeon and the presence or absence of adjacent joint OA (based on an independently reviewed preoperative MRI scan). Participants were randomised 1:1 to either TAR or ankle arthrodesis. The primary outcome was the change in the Manchester Oxford Foot & Ankle Questionnaire (MOXFQ) walking/standing domain scores between pre-operation and 52 weeks post- operation. Secondary outcomes measures included FAAM; FAAM (ADL); and Sport subscale scores. Quality of life was measured using the EQ-5D-5L. Total range of tibia to floor motion was measured using a validated method. Health economic analysis used mean incremental cost per quality-adjusted life years (QALY) gained. Analysis was by intention to treat. The trial registration is ISRCTN60672307. Results: Of 933 eligible patients 303 were randomised. 282 underwent surgery. Mean age 68 (71% male). Aetiology was post- trauma in 55.3%, and inflammatory in 7.1%. Groups were well balanced at baseline on all parameters. 54% TARs were fixed bearing. 61% of fusions were performed arthroscopically. At 2 years the adjusted mean difference in the change in MOXFQ W/S between TAR & AF was -4.4(95% CI -11.38 to 2.68, p=0∙23). Post hoc analysis of the commonest implant type (fixed bearing TAR) did show a statistically significant improvement over AF (p=0∙04, -8.9, 95% CI -17.2 to -0.6). Secondary outcomes, EQ5D-VAS and FAAM were significant. Complications included wound healing issues (13.8% vs 5.5%); nerve injuries (4.3% vs 0.7%). 11.8% of AF patients had plain radiographic evidence of non-union but only 6.9% had symptoms. Reoperation rate was 7.2% for TAR vs 5.2% for AF; and revision rate was 0.7% for TAR vs 2.8% for AF. Conclusion: Patients improved in all outcomes in both arms. We did not show a significant difference in our primary outcome measure between TAR and AF overall(p=0.23), but did show significance when fixed bearing TAR alone was compared against AF(p=0.04). Secondary outcomes did show significance. Adjacent joint arthritis increases the size of effect noted between arms. There were more wound healing issues and nerve injuries in TAR group. The symptomatic non-union rate for AF is 6.9%. TAR is likely to be cost-effective compared to AF at the NICE cost-effectiveness threshold of £20,000 per Quality Adjusted Life Year gained over the patients' lifetime.

Category: Hindfoot; Midfoot/Forefoot Introduction/Purpose: Peritalar subluxation (PTS) of the hindfoot is a critical finding in Progressive Collapsing Foot Deformity (PCFD). Subluxation of the middle facet and sinus tarsi recently been shown to represent essential markers of pronounced and potentially progressive deformity. Weightbearing CT (WBCT) imaging and three-dimensional (3D) distancing coverage maps (CM) allow a complete and accurate assessment of PTS markers across the entire peritalar surface. This prospective comparative study aimed to assess the effectiveness of joint-sparing realignment surgical treatment for flexible PCFD in reducing PTS and to correlate the improvement with patient-reported outcomes (PROs). We hypothesized that would significantly improve PTS markers, mainly decreasing sinus tarsi coverage/impingement and middle facet subluxation, and that this improvement would correlate with increased PROs. Methods: In this IRB-approved prospective and comparative study, we enrolled patients with flexible PCFD, no prior surgeries, and failed conservative treatment. Included females/3 males, mean age 57.2, range 37-74) underwent joint-sparing surgical realignment procedure by a single surgeon. Standing weightbearing CT (WBCT) was complete 3-months postoperatively. Following automatic bone segmentation, 3D distance maps (DMs) of the entire peritalar surface were generated, and coverage of the subtalar joint (anterior, middle, and posterior) and sinus tarsi were assessed as markers of PTS. Joint coverage was defined as the percentage of articular space where DMs were

Abstract Background The total ankle replacement versus ankle arthrodesis (TARVA) trial aims to determine which surgical procedure confers the greatest improvement in pain-free function for patients with end-stage ankle osteoarthritis. Both procedures are effective but there has not yet been a direct comparison to establish which is superior. This article describes the statistical analysis plan for this trial as an update to the published protocol. It is written prior to the end of patient follow-up, while the outcome of the trial is still unknown. Design and methods TARVA is a randomised, un-blinded, parallel group trial of total ankle replacement versus ankle arthrodesis. The primary outcome is the Manchester-Oxford Foot Questionnaire walking/standing domain score at 52 weeks post-surgery. Secondary outcomes include measures of pain, social interaction, physical function, quality of life, and range of motion. We describe in detail the statistical aspects of TARVA: the outcome measures, the sample size calculation, general analysis principles including treatment of missing data, the planned descriptive statistics and statistical models, and planned subgroup and sensitivity analyses. Discussion The TARVA statistical analysis will provide comprehensive and precise information on the relative effectiveness of the two treatments. The plan will be implemented in January 2020 when follow-up for the trial is completed. Trial registration ISRCTN registry number 60672307, ClinicalTrials.gov registration number NCT02128555. Registered 1 May 2014. Recruitment started in January 2015 and ended in January 2019.

Category: Ankle; Hindfoot; Other Introduction/Purpose: Peritalar subluxation (PTS) of the hindfoot is a critical finding in Progressive Collapsing Foot Deformity (PCFD). Subluxation of the middle facet and sinus tarsi impingement have recently been shown to represent essential markers of pronounced and potentially progressive deformity. Weightbearing CT (WBCT) imaging and three-dimensional (3D) distance (DM) and coverage maps (CM) allow a complete and accurate assessment of PTS markers across the entire peritalar surface. This prospective comparative study aimed to assess the effectiveness of joint-sparing realignment surgical treatment for flexible PCFD in reducing PTS and to correlate the improvement with patient-reported outcomes (PROs). We hypothesized that surgical treatment would significantly improve PTS markers, mainly decreasing sinus tarsi coverage/impingement and middle facet subluxation, and that this improvement would correlate with increased PROs. Methods: In this IRB-approved prospective and comparative study, we enrolled patients with flexible PCFD, no prior surgeries, and failed conservative treatment. Included patients (n=10, 7 females/3 males, mean age 57.2, range 37-74) underwent joint-sparing surgical realignment procedure by a single surgeon. Standing weightbearing CT (WBCT) was completed preoperatively and 3- months postoperatively. Following automatic bone segmentation, 3D distance maps (DMs) of the entire peritalar surface were generated, and coverage of the subtalar joint articular facets (anterior, middle, and posterior) and sinus tarsi were assessed as markers of PTS. Joint coverage was defined as the percentage of articular space where DMs were

Category: Ankle Introduction/Purpose: Recently, weightbearing computed tomography (WBCT) has been utilized to provide more comprehensive and accurate assessment of complex foot and ankle deformities, notably to diagnose and stage Progressive Collapsing Foot Deformity (PCFD). The 3D data provided by WBCT has enabled the developed of novel tools like distance mapping (DM), coverage mapping (CM), and volume measurements. Over the past year, novel DM and CM have shown promise in providing sensitive automated measures of peritalar subluxation, a major component of PCFD. However, the early effects of PCFD on the tibiotalar joint have not yet been quantified. This study sought to use DM and CM to objectively characterize the effects of PCFD on the tibiotalar and tibiofibular joints. We hypothesized that changes seen in early PCFD will be identified. Methods: IRB approval for retrospective review of patient data from 2014-2020 was obtained to identify patients with clinical and radiographic diagnoses of PCFD. The first consecutive 20 patients with symptomatic flexible PCFD and high-resolution weightbearing CT examination without arthritis that had not undergone prior surgery were selected and compared with 20 controls. Fully automated volume measurements of the syndesmosis at 1cm, 3cm, and 5cm from the tibiotalar joint were performed as well as of the medial and lateral tibiotalar gutters based on models created in Disior Bonelogic. Distance Maps (DMs) were obtained for the tibiofibular incisura, tibiotalar joint, and gutters. Coverage maps (CMs) were created using the measured 3DDMs to identify joint interaction, subluxation, and impingement. Data were checked for normality using the Shapiro- Wilk W test. Two-tailed independent samples student t-tests or Wilcoxon Tests were used to assess differences between groups. Results: There were significant decreases in coverage of all 3 anterior regions of the tibiotalar joint in PCFD patients when compared to controls along with corresponding significant increases in coverage of all 3 posterior regions (Figure). There were no significant differences in mean or minimum distances in any region of the tibiotalar joint surface. Significant increases in average and minimum DMs of the anterior medial (36%, p

Category: Ankle Arthritis; Ankle; Other Introduction/Purpose: Both ankle replacement and ankle arthrodesis are offered as treatments to patients with end stage ankle osteoarthritis. Systematic reviews have confirmed that both procedures are effective but there has never been a robust randomised multicentre level I study comparing the two treatments. Our objective was to investigate and compare the clinical and cost effectiveness and complication rates of ankle replacement against ankle arthrodesis in the treatment of end-stage ankle osteoarthritis in patients aged 50-85 years. Methods: 17 NHS centres and 35 surgeons across the United Kingdom participated. Formal Ethics committee approvals were obtained. A Trial Management Group was overseen by a Trial Steering Committee, and an Independent Data Monitoring Committee. Randomisation was carried out using a secure on-line service and was stratified by surgeon and the presence or absence of adjacent joint OA (based on an independently reviewed preoperative MRI scan). Participants were randomised 1:1 to either TAR or ankle fusion. The primary outcome was the change in the Manchester Oxford Foot & Ankle Questionnaire (MOXFQ) walking/standing domain scores between pre-operation and 52 weeks post-operation. Secondary outcomes measures included FAAM; FAAM (ADL); and Sport subscale scores. Quality of life was measured using the EQ-5D-5L. Total range of motion was measured using a validated method. Radiological parameters and adverse events were captured. Health economic analysis used mean incremental cost per quality-adjusted life years (QALY) gained. Results: 1600 patients were screened for eligibility. 330 participants were consented and 303 were randomised; 282 underwent surgery and attended follow-up visits. Mean age was 68 years (71% male). The aetiology of OA was post-trauma in 60%, with 6% patients having inflammatory OA. 42% had MRI evidence of OA in the adjacent joints. The groups were well balanced at baseline on all other parameters including deformity, range of motion and baseline clinical and quality of life scores.42% had MRI evidence of OA in the adjacent joints. 54% TARs used were fixed bearing; 46% were mobile bearing. 61% of fusions were performed arthroscopically. We present all outcomes including adverse effects (death; thromboembolic events; reoperation and revision); radiological findings; and range of motion. We also present subgroup analyses looking at the performance of fixed versus mobile bearing implants; differences by age; and by the presence or absence of adjacent joint OA. Conclusion: This is the first publicly funded, multicentre, prospective, randomised clinical trial comparing the clinical and cost effectiveness of ankle replacement against ankle fusion. It is also the first study in surgery to have detailed prospectively captured health economic data to be able to feed into the reimbursement discussions on these life transforming treatments. Due to contractual requirements of the funders the formal results cannot be released until the final report has been submitted for peer review which will not happen until the end of April 2021. The paper is submitted on behalf of the TARVA Study Group.

Category Ankle Arthritis; Ankle Introduction/Purpose: This is the first report from the UK INFINITY study. This is a multicentre, non-inventor, prospective observational study of 504 INFINITY fixed bearing total ankle arthroplasties. We report our early experience, complications, radiographic and functional outcomes of this prosthesis. Methods: Patients were recruited from 11 specialist centres between June 2016 and November 2019. Demographic, radiographic, and functional outcome data (Ankle Osteoarthritis Scale, Manchester Oxford Questionnaire and Euroquol 5D-5L) were collected preoperatively, at 6 months (454 patients), 1 year (328 patients) and 2 years (104 patients). The average age was 67.8 (range 23.9 to 88.5) and average BMI 29.9 (18.9 to 48.0). The COFAS grading system was used to stratify deformity. There were 259 (51.4%) COFAS Type 1, 122 (24.2%) COFAS Type 2, 32 (6.3%) COFAS 3 and 87 (17.3%) COFAS type 4. 38 patients (7.54%) presented with inflammatory arthritis. 101 (20.0%) of implantations utilised patient specific instrumentation (Prophecy). 169 (33.5%) of patients underwent an additional procedure at the time of surgery. Early and late complications and reoperations were recorded as adverse events. Radiographs were assessed for lucencies, cysts and/or subsidence. Results: There was a significant (p