Knee joint distraction (KJD) has been associated with clinical and structural improvement and synovial fluid (SF) marker changes. However, structural changes have not yet been shown satisfactorily in regular care, since radiographic acquisition was not fully standardized. AI-based modules have shown great potential to reduce reading time, increase inter-reader agreement and therefore function as a tool for treatment outcome assessment. The objective was to analyse structural changes after KJD in patients using this AI-based measurement method, and relate these changes to clinical outcome and SF markers.

20 knee OA patients (<65 years old) were included in this study. KJD treatment was performed using an external fixation device, providing 5 mm distraction for 6 weeks. SF was aspirated before, during and immediately after treatment. Weight-bearing antero-posterior knee radiographs and WOMAC questionnaires were collected before and ~one year after treatment. Radiographs were analysed with the Knee Osteoarthritis Labelling Assistant (KOALA, IB Lab GmbH, Vienna, Austria), and 10 pre-defined biomarker levels in SF were measured by immunoassay. Radiographic one-year changes were analysed and linear regression was used to calculate associations between changes in standardized joint space width (JSW) and WOMAC, and changes in JSW and SF markers.

After treatment, radiographs showed an improvement in Kellgren-Lawrence grade in 7 of 16 patients that could be evaluated; 3 showed a worsening. Joint space narrowing scores and continuous JSW measures improved especially medially. A greater improvement in JSW was significantly associated with a greater improvement in WOMAC pain (β=0.64;p=0.020). A greater increase in MCP1 (β=0.67;p=0.033) and lower increase in TGFβ1 (β=-0.787;p=0.007) were associated with JSW improvement.

Despite the small number of patients, also in regular care KJD treatment shows joint repair as measured automatically on radiographs, significantly associated with certain SF marker change and even with clinical outcome.

In relation to regenerative therapies in osteoarthritis and cartilage repair, mesenchymal stromal cells (MSCs) have immunomodulatory functions and influence macrophage behaviour. Macrophages exist as a spectrum of pro-(M1) and anti-(M2) inflammatory phenotypic subsets. In the context of cartilage repair, we investigated MSC-macrophage crosstalk, including specifically the priming of cartilage cells by macrophages to achieve a regenerative rather than fibrotic outcome. Human monocytes were isolated from blood cones and differentiated towards M1 and M2 macrophages. Monocytes (Mo), M1 and M2 macrophages were cultured directly and indirectly (trans-well system) with human bone marrow derived MSCs. MSCs were added during M1 polarisation and separately to already induced M1 cells. Outcomes (M1/M2 markers and ligands/receptors) were evaluated using RT-qPCR and flow cytometry. Influence on chondrogenesis was assessed by applying M1 and M2 macrophage conditioned media (CM) sequentially to cartilage derived cells (recapitulating an acute injury environment). RT-qPCR was used to evaluate chondrogenic/fibrogenic gene transcription. The ratio of M2 markers (CD206 or CD163) to M1 markers (CD38) increased when MSCs were added to Mo/M1 macrophages, regardless of culture system used (direct or indirect). Pro-inflammatory markers (including TNFβ) decreased. CXCR2 expression by both M1 macrophages and MSCs decreased when MSCs were added to differentiated M1 macrophages in transwell. When adding initially M1 CM (for 12 hours) followed by M2 CM (for 12 hours) sequentially to chondrocytes, there was a significant increase of Aggrecan and Collagen type 2 gene expression and decrease in fibroblastic cell surface markers (PDPN/CD90). Mo/M1 macrophages cultured with MSCs, directly or indirectly, are shifted towards a more M2 phenotype. Indirect culture suggests this effect can occur via soluble signaling mediators. Sequential exposure of M1CM followed by M2CM to chondrocytes resulted in increased chondrogenic and reduced fibrotic gene expression, suggesting that an acute pro-inflammatory stimulus may prime chondrocytes before repair.

3D accurate measurements of the skeletal structures of the foot, in physiological and impaired subjects, are now possible using Cone-Beam CT (CBCT) under real-world loading conditions. In detail, this feature allows a more realistic representation of the relative bone-bone interactions of the foot as they occur under patient-specific body weight conditions. In this context, varus/valgus of the hindfoot under altered conditions or the thinning of plantar tissues that occurs with advancing age are among the most complex and interesting to represent, and numerous measurement proposals have been proposed. This study aims to analyze and compare these measurements from CBCT in weight-bearing scans in a clinical population. Sixteen feet of diabetic patients and ten feet with severe adult flatfoot acquired before/after corrective surgery underwent CBCT scans (Carestream, USA) while standing on the leg of interest. Corresponding 3D shapes of each bone of the shank and hindfoot were reconstructed (Materialise, Belgium). Six different techniques found in the literature were used to calculate the varus/valgus deformity, i.e., the inclination of the hindfoot in the frontal plane of the shank, and the distance between the ground and the metatarsal heads was calculated along with different solutions for the identification of possible calcifications. Starting with an accurate 3D reconstruction of the skeletal structures of the foot, a wide range of measurements representing the same angle of hindfoot alignment were found, some of them very different from each other. Interesting correlations were found between metatarsal height and subject age, significant in diabetic feet for the fourth and fifth metatarsal bones. Finally, CBCT allows 3D assessment of foot deformities under loaded conditions. The observed traditional measurement differences and new measurement solutions suggest that clinicians should consider carefully the anatomical and functional concepts underlying measurement techniques when drawing clinical and surgical conclusions.

Residual tumor cells left in the bone defect after malignant bone tumor resection can result in local tumor recurrence and high mortality. Therefore, ideal bone filling materials should not only aid bone reconstruction or regeneration, but also exert local chemotherapeutic efficacy. However, common bone substitutes used in clinics are barely studied in research for local delivery of chemotherapeutic drugs. Here, we aimed to use facile manufacturing methods to render polymethylmethacrylate (PMMA) cement and ceramic granules suitable for local delivery of cisplatin to limit bone tumor recurrence.

Porosity was introduced into PMMA cement by adding 1-4% carboxymethylcellulose (CMC) containing cisplatin, and chemotherapeutic activity was rendered to two types of granules via adsorption. Then, mechanical properties, porosity, morphology, drug release kinetics, ex vivo reconstructive properties of porous PMMA and in vitro anti-cancer efficacy against osteosarcoma cells were assessed. Morphologies, molecular structures, drug release profiles and in vitro cytostatic effects of two different drug-loaded granules on the proliferation of metastatic bone tumor cells were investigated.

The mechanical strengths of PMMA-based cements were sufficient for tibia reconstruction at CMC contents lower than 4% (≤3%). The concentrations of released cisplatin (12.1% and 16.6% from PMMA with 3% and 4% CMC, respectively) were sufficient for killing of osteosarcoma cells, and the fraction of dead cells increased to 91.3% within 7 days. Functionalized xenogeneic granules released 29.5% of cisplatin, but synthetic CaP granules only released 1.4% of cisplatin over 28 days. The immobilized and released cisplatin retained its anti-cancer efficacy and showed dose-dependent cytostatic effects on the viability of metastatic bone tumor cells.

Bone substitutes can be rendered therapeutically active for anticancer efficacy by functionalization with cisplatin. As such, our data suggest that multi-functional PMMA-based cements and cisplatin-loaded granules represent viable treatment options for filling bone defects after bone tumor resection.

Introduction

With advances in mobile application, digital health is being increasingly used for remote and personalised care. Patient education, self-management and tele communication is a crucial factor in optimising outcomes.

BACKGROUND

Theatre-listed trauma patients routinely require two ‘group and save’ blood-bank samples, in case they need perioperative transfusion. The Welsh Blood Service (WBS) need patients to have one recorded sample from any time in the last 10 years. A second sample, to permit cross-matching and blood issuing, must be within 7 days of transfusion (or within 48 hours if the patient is pregnant, or has been transfused within the last 3 months). The approximate cost of processing a sample is £15.00.

Results in patients undergoing total hip arthroplasty (THA) for femoral head osteonecrosis (ON) when compared with primary osteoarthritis (OA) are controversial. Different factors like age, THA type or surgical technique may affect outcome. We hypothesized that patients with ON had an increased revision rate compared with OA. We analysed clinical outcome, estimated the survival rate for revision surgery, and their possible risk factors, in two groups of patients.

In this retrospective cohort analysis of our prospective database, we assessed 2464 primary THAs implanted between 1989 and 2017. Patients with OA were included in group 1, 2090 hips; and patients with ON in group 2, 374 hips. In group 2 there were more men (p<0.001), patients younger than 60 years old (p<0.001) and with greater physical activity (p<0.001). Patients with lumbar OA (p<0.001) and a radiological acetabular shape type B according to Dorr (p<0.001) were more frequent in group 1. Clinical outcome was assessed according to the Harris Hip Score and radiological analysis included postoperative acetabular and femoral component position and hip reconstruction. Kaplan-Meier survivorship analysis was used to estimate the cumulative probability of not having revision surgery for different reasons. Univariate and multivariate Cox regression models were used to assess risk factors for revision surgery.

Clinical improvement was better in the ON at all intervals. There were 90 hips revised, 68 due to loosening or wear, 52 (2.5%) in group 1, and 16 (4.3%) in group 2. Overall, the survival rate for revision surgery for any cause at 22 years was 88.0 % (95% CI, 82-94) in group 1 and 84.1% (95% CI, 69 – 99) in group 2 (p=0.019). Multivariate regression analysis showed that hips with conventional polyethylene (PE), compared with highly-cross linked PEs or ceramic-on-ceramic bearings, (p=0.01, Hazard Ratio (HR): 2.12, 95% CI 1.15-3.92), and cups outside the Lewinnek´s safe zone had a higher risk for revision surgery (p<0.001, HR: 2.57, 95% CI 1.69-3.91).

Modern highly-cross linked PEs and ceramic-on-ceramic bearings use, and a proper surgical technique improved revision rate in patients undergoing THA due to ON compared with OA.

The current procedures being applied in the clinical setting to address osteoporosis-related delayed union and nonunion bone fractures have been found to present mostly suboptimal outcomes. As a result, bone tissue engineering (BTE) solutions involving the development of implantable biomimetic scaffolds to replace damaged bone and support its regeneration are gaining interest. The piezoelectric properties of the bone tissue, which stem primarily from the significant presence of piezoelectric type I collagen fibrils in the tissue's extracellular matrix (ECM), play a key role in preserving the bone's homeostasis and provide integral assistance to the regeneration process. However, despite their significant potential, these properties of bone tend to be overlooked in most BTE-related studies. In order to bridge this gap in the literature, novel hydroxyapatite (HAp)-filled osteoinductive and piezoelectric poly(vinylidene fluoride-co-tetrafluoroethylene) (PVDF-TrFE) electrospun nanofibers were developed to replicate the bone's fibrous ECM composition and electrical features. Different HAp nanoparticle concentrations (1–10%, wt%) were tested to assess their effect on the physicochemical and biological properties of the resulting fibers. The fabricated scaffolds displayed biomimetic collagen fibril-like diameters, while also presenting mechanical features akin to type I collagen. The increase in HAp presence was found to enhance both surface and piezoelectric properties of the fibers, with an improvement in scaffold wettability and increase in β-phase nucleation (translating to increased piezoelectricity) being observed. The HAp-containing scaffolds also exhibited an augmented bioactivity, with a more comprehensive surface mineralization of the fibers being obtained for the scaffolds with the highest HAp concentrations. Improved osteogenic differentiation of seeded human mesenchymal stem/stromal cells was achieved with the addition of HAp, as confirmed by an increased ALP activity, calcium deposition and upregulated expression of key osteogenic markers. Overall, our findings highlight, for the first time, the potential of combining PVDF-TrFE and HAp to develop electroactive and osteoinductive nanofibers for BTE.

Acknowledgements: The authors thank FCT for funding through the projects InSilico4OCReg (PTDC/EME-SIS/0838/2021), OptiBioScaffold (PTDC/EME-SIS/4446/2020) and BioMaterARISES (EXPL/CTM-CTM/0995/2021), the PhD scholarship (2022.10572.BD) and to the research institutions iBB (UIDB/04565/2020 and UIDP/04565/2020) and Associate Laboratory i4HB (LA/P/0140/2020).

Aims

The microbiological detection of microorganisms plays a crucial role in the diagnosis as well as in the targeted systemic and local antibiotic therapy of periprosthetic infections (PJI). Despite extensive efforts to improve the sensitivity of current culture methods, the rate of culture-negative infections is approximately 10–20% of all PJI. This study investigates an preanalytical algorithm (culture collection and direct processing in the OR) to potentially increasing culture yield in patients with PJI.

Aim

The aim of this study was to investigate the clinical relevance of an isolated positive sonication fluid culture (SFC) in patients who underwent revision surgery of a prosthetic joint. We hypothesized that cases with a positive SFC have a higher rate of infection and prosthesis failure during follow-up compared to controls with a negative SFC.

Background

Advice and education are considered vital components of back pain care within national guidelines. However, a recent systematic review only found low grade evidence for a small average effect. They also reported wide heterogeneity in intervention design and delivery. This review aimed to understand why intervention design varied and what limited effectiveness by examining the underlying theoretical foundations of the studies from that review.

Traditionally, sports Injuries have been sub-optimally managed through Emergency Departments (ED) in the public health system due to a lack of adequate referral processes. Fractures are ruled out through plain radiographs followed by a reactive process involving patient initiated further follow up and investigation. Consequently, significant soft tissue and chondral injuries can go undiagnosed during periods in which early intervention can significantly affect natural progression. The purpose of this quality improvement project was to assess the efficacy of an innovative Sports Injury Pathway introduced to detect and treat significant soft tissue injuries.

A Sports Injury Pathway was introduced at Fiona Stanley Hospital (WA, Australia) in April 2019 as a collaboration between the ED, Physiotherapy and Orthopaedic Departments. ED practitioners were advised to have a low threshold for referral, especially in the presence of a history of a twisting knee injury, shoulder dislocation or any suggestion of a hip tendon injury. All referrals were triaged by the Perth Sports Surgery Fellow with early follow-up in our Sports Trauma Clinics with additional investigations if required. A detailed database of all referrals was maintained, and relevant data was extracted for analysis over the first 3 years of this pathway.

570 patients were included in the final analysis. 54% of injuries occurred while playing sport, with AFL injuries constituting the most common contact-sports injury (13%). Advanced Scope Physiotherapists were the largest source of referrals (60%). A total of 460 MRI scans were eventually ordered comprising 81% of total referrals. Regarding Knee MRIs, 86% identified a significant structural injury with ACL injuries being the most common (33%) followed by isolated meniscal tears (16%) and multi-ligament knee injuries (11%). 95% of Shoulder MRI scans showed significant pathology. 39% of patients required surgical management, and of these 50% were performed within 3 months from injury.

The Fiona Stanley Hospital Sports Injury Pathway has demonstrated its clear value in successfully diagnosing and treating an important cohort of patients who present to our Emergency Department. This low threshold/streamlined referral pathway has found that the vast majority of these patients suffer significant structural injuries that may have been otherwise missed, while providing referring practitioners and patients access to prompt imaging and high-quality Orthopaedic sports trauma services. We recommend the implementation of a similar Sports Injury Pathway at all secondary and tertiary Orthopaedic Centres.

Children with osteogenesis imperfecta (OI) frequently present with coxa vara (CV). Skeletal fragility, severe deformity and limited fixation options make this a challenging condition to correct surgically. Our study aimed to determine the efficacy of the Fassier technique to correct CV and determine the complication rate.

Retrospective, descriptive case series from a tertiary hospital. We retrospectively reviewed records of a cohort of eight children (four females, 12 hips) with OI (6/8 Sillence type III, 2/8 type IV) who had surgical treatment with Fassier technique for CV between 2014 and 2020.

Inclusion Criteria: All patients with CV secondary to OI treated surgically with Fassier technique.

Exclusion Criteria: Patients older than 18 years; Patients with CV treated non-operatively or by surgical technique different to Fassier technique.

Data relating to the following parameters was collected and analyzed: demographic data, pre- and postoperative neck shaft angle (NSA), complications and NSA at final follow-up.

The mean age at operation was 5.8 years (range 2–10). The mean NSA was corrected from 96.8° preoperatively to 137º postoperatively. At a mean follow-up of 38.6 months, the mean NSA was maintained at 133°, and 83% (10/12) of hips had an NSA that remained greater than 120°. There was a 42% (5/12) complication rate: three Fassier–Duval rods failed to expand after distal epiphyseal fixation was lost during growth; one Rush rod migrated through the lateral proximal femur cortex with recurrent coxa vara; and one Rush rod migrated proximally and required rod revision.

The Fassier technique effectively corrected CV in children with moderate and progressively deforming OI. The deformity correction was maintained in the short term. The complication rate was high, but mainly related to the failed expansion of the Fassier–Duval rods.

Local anatomical abnormalities vary in congenital hip disease patients. Authors often present early to mid-term total hip arthroplasty clinical outcomes using different techniques and implants randomly on patients with different types of the disease, making same conclusions difficult.

We report long term outcomes (13 to 23 years) of the treatment of low and high dislocation cases (separately) with total hip arthroplasty using TM technology acetabular cups (Implex initially and then Zimmer) and short fluted conical (Zimmer) femoral stems.

From 2000 to 2010, 418 congenital hip disease hip joints were treated in our department with total hip arthroplasty. According to Hartofilakidis et al's classification, 230 hips had dysplasia, 101 low dislocation, (group A) and 87 high dislocation (group B). Pre-operative and post-operative values, at regular intervals, of HHS, SF-12, WOMAC, OHS and HOOS were available for all patients. Patient, surgeon and implant related failures and complications were recorded for all patients.

In all cases an attempt was made to restore hip center of rotation. In group A the average lengthening was 2.8 cm (range: 1 to 4.2) and in group B 5.7 cm (range: 4.2 to 11). In both groups, no hips were revised due to aseptic loosening of either the acetabular cup or the femoral stem. In group A, a cumulative success rate of 95.6% (95% confidence interval, 92.7% – 97.4%) and in group B a cumulative success rate of 94.8% (95% confidence interval, 92.6%–96.9%) was recorded, at 20 years, with revision for any reason as an end point. No s.s. differences were found between groups when mean values of HHS, SF-12, WOMAC and OKS were compared.

Satisfactory long-term clinical outcomes can be achieved in treating different types of congenital hip disease when appropriate surgical techniques combined with “game changing” implants are used.

Abstract

Abstract

Abstract

The purpose was to determine the lifetime risk of re-operation due to specific complications related to dual mobility using re-operation as a competing risk, excluding loosening, periprosthetic fracture, and infection.

1503 mono-block dual mobility total hip arthroplasty (DM-THAs). Defining the re-operation when anesthesia (for dislocation) and revision when the implant changed. Surgery (801 for primary, 702 for revision with 201 for recurrent dislocation and 501 for loosening) performed between 1990 and 2020 in average 81-year-old (range 50–102) patients, with 522 living patients at 10 years follow-up.

During the first month, outer dislocation (60 cases; 4%) was the cause re-operation (1% among primary and 6 % among revisions). Twenty-four intra-prosthetic dislocations (IPD) were an iatrogenic consequence of a failed closed reduction (reduction maneuver dissociating the inner head) with 1.6% revision.

Between 1 month and 1 year, 22 new outer dislocations, while 25 of the 60 “first month” dislocations had recurrent dislocation. Fifteen other IPDs as iatrogenic consequences were observed. At one year, the cumulative revision was 3% (49 of 82 dislocations).

Between 1- 10-year FU, 132 other dislocations, and 45 other revisions for dislocations were observed. Corrosion was another cause of revision (37 cases): between the cobalt-chromium shell and the femoral neck (23 hips), or 14 crevice corrosion between the trunnion and the metal head (trunnion damage).

In summary, at 10-year: dislocation first cause of re-operation (214 anesthesia, 14%), while among 131 revisions (8.9 %) the 55 iatrogenic intra-prosthetic dislocations were the first revision cause before 39 recurrent dislocations and 37 corrosions.

The 522 patients followed ten years or more had a 15% risk revision due to DM specific complications during their lifetime and 10% more risk associated with loosening (6%), periprosthetic fracture (2%) and infection (2%).

Complex regional pain syndrome type 1 (CRPS-I) is a devastating complication that can occur after limb extremity injuries. The effectiveness of vitamin C in preventing CRPS-I incidence is debatable. Therefore, we conducted a systematic review and meta-analysis to assess the role of vitamin C in CRPS-I prevention and its effect on pain score, functional outcomes and complications rate after wrist, ankle, and foot fractures.

We searched Medline, Embase, the Cochrane Library, Clinicaltrial.gov, and Google Scholar from infinity to May 2021 for relevant studies comparing the incidence of CRPS-I with administration of perioperative vitamin C versus placebo after wrist, ankle, and foot fractures. Continuous data such as functional outcomes and pain scores were pooled as mean differences (MD), whist dichotomous variables such as the incidence of CRPS-I and complications were pooled as odds ratios (OR), with 95% confidence interval (CI). Data analyses was done using R software (meta package, version 4.9-0) for Windows.

Eight studies, including two quasi-experimental studies, were included. The timeframe for vitamin C administration ranged from 42 to 50 days post-injury and/or surgical fixation and the dosage was either 500 mg or 1000 mg. The results showed that vitamin C was associated with a lower rate of CRPS-I relative to a placebo (OR 0.33, 95% CI [0.17, 0.63]). No significant difference was found between vitamin C and placebo in terms of complications (OR 1.90, 95% CI [0.99, 3.65]), functional outcomes (MD 6.37, 95% CI [-1.40, 14.15]), and pain scores (MD −0.14, 95% CI [-1.07, 0.79]).

The findings demonstrate that when compared to placebo, at least 42 days of vitamin C prophylaxis is associated with prevention of CRPS-I following wrist, ankle, and foot fractures, irrespective of vitamin C dosage or fracture type. No significant differences were found with secondary outcomes.

Ankle fractures represent the third most common fragility fracture seen in elderly patients following hip and distal radius fractures. Non-operative management of these see complication rates as high as 70%. Open reduction and internal fixation (ORIF) has complication rates of up to 40%. With either option, patients tend to be managed with a non-weight bearing period of six weeks or longer. An alternative is the use of a tibiotalocalcaneal (TTC) nail. This provides a percutaneous treatment that enables the patient to mobilise immediately. This case-series explores the efficacy of this device in a broad population, including the highly comorbid and cognitively impaired.

We reviewed patients treated with TTC nail for acute ankle fractures between 2019 and 2022. Baseline and surgical data were collected. Clinical records were reviewed to record any post-operative complication, and post-operative mobility status and domicile. 24 patients had their ankle fracture managed with TTC nailing. No intra-operative complications were noted. There were six (27%) post-operative complications; four patients had loosening of a distal locking screw, one significant wound infection necessitating exchange of nail, and one pressure area from an underlying displaced fracture fragment. All except three patients returned to their previous domicile. Just over two thirds of patients returned to their baseline level of mobility.

This case-series is one of the largest and is also one of the first to include cognitively impaired patients. Our results are consistent with other case-series with a favourable complication rate when compared with ORIF in similar patient groups. The use of a TTC nail in the context of acute, geriatric ankle trauma is a simple and effective treatment modality. This series shows acceptable complication rates and the majority of patients are able to return to their baseline level of mobility and domicile.

Distal radius fractures are common in South Africa. Accurate, decisive radiographic parameter interpretation is key in appropriate management. Digital radiographic facilities are rare in the public setting and goniometer usage is known to be low, thus, visual estimates are the primary form of radiographic assessment. Previous research associated orthopaedic experience with accuracy of distal radius fracture parameter estimation but, oftentimes, doctors treating orthopaedic patients are not experienced in orthopaedics.

A cross-sectional questionnaire including four distal radius fracture radiographs administered to 149 orthopaedic doctors at three Johannesburg teaching hospitals. Participants grouped into ranks of: consultants (n=36), registrars (n=41), medical officers (n=20) and interns (n=52). Participants visually estimated values of distal radius fracture parameters, stated whether they would accept the position of the fractures and stated their percentage of routine usage of goniometers in real practice.

The registrar group was most accurate in visually estimating radial height, whilst the interns were least accurate (p=0.0237). The consultant, registrar and medical officer groups were equally accurate in estimating radial inclination whilst the intern group was the least accurate (p<0.0001). The consultant and registrar group were equally accurate at estimating volar tilt, whilst the medical officer and intern groups were least accurate (p<0.0001). The Gwet's AC agreement was 0.1612 (p=0.047) for acceptance of position of the first radiograph, 0.8768 (p<0.0001) for the second, 0.8884 (p<0.0001) for the third and 0.8064 (p<0.0001) for the fourth. All groups showed no difference in goniometer usage, using them largely 0–25% of practice (p=0.1937).

The study found that accuracy in visual estimations of distal radius fracture parameters was linked to orthopaedic experience but not linked to routine practice goniometer usage, which was minimal across all groups. Inter-rater agreement on acceptability of fracture position is potentially dependent on severity of deviation from acceptable parameters.

There is a paucity of mid-term data on modular dual-mobility (MDM) constructs versus large (≥40 mm) femoral heads (LFH) in revision total hip arthroplasties (THAs). The purpose of this study was to update our prior series at 10 years, with specific emphasis on survivorships free of re-revision for dislocation, any re-revision, and dislocation.

We identified 300 revision THAs performed at a single tertiary care academic institution from 2011 to 2014. Aseptic loosening of the acetabular component (n=65), dislocation (n=59), and reimplantation as part of a two-stage exchange protocol (n=57) were the most common reasons for index revision. Dual-mobility constructs were used in 124 cases, and LFH were used in 176 cases. Mean age was 66 years, mean BMI was 31 kg/m², and 45% were female. Mean follow-up was 7 years.

The 10-year survivorship free of re-revision for dislocation was 97% in the MDM cohort and 91% in the LFH cohort with a significantly increased risk of re-revision for dislocation in the LFH cohort (HR 5.2; p=0.03). The 10-year survivorship free of any re-revision was 90% in the MDM cohort and 84% in the LFH cohort with a significantly increased risk of any re-revision in the LFH cohort (HR 2.5; p=0.04). The 10-year survivorship free of any dislocation was 92% in the MDM cohort and 87% in the LFH cohort. There was a trend towards an increased risk of any dislocation in the LFH cohort (HR 2.3; p=0.06).

In this head-to-head comparison, revision THAs using MDM constructs had a significantly lower risk of re-revision for dislocation compared to LFH at 10 years. In addition, there was a trend towards lower risk of any dislocation.

Level of Evidence: IV

Fractures of the distal radius are common, and form a considerable proportion of the trauma workload. We conducted a study to examine the patterns of injury and treatment for adult patients presenting with distal radius fractures to a major trauma centre serving an urban population.

We undertook a retrospective cohort study to identify all patients treated at our major trauma centre for a distal radius fracture between 1 June 2018 and 1 May 2021. We reviewed the medical records and imaging for each patient to examine patterns of injury and treatment. We undertook a binomial logistic regression to produce a predictive model for operative fixation or inpatient admission.

Overall, 571 fractures of the distal radius were treated at our centre during the study period. A total of 146 (26%) patients required an inpatient admission, and 385 surgical procedures for fractures of the distal radius were recorded between June 2018 and May 2021. The most common mechanism of injury was a fall from a height of one metre or less. Of the total fractures, 59% (n = 337) were treated nonoperatively, and of those patients treated with surgery, locked anterior-plate fixation was the preferred technique (79%; n = 180).

The epidemiology of distal radius fractures treated at our major trauma centre replicated the classical bimodal distribution described in the literature. Patient age, open fractures, and fracture classification were factors correlated with the decision to treat the fracture operatively. While most fractures were

Abstract

Atypical femoral fracture non-union (AFFNU) is both, rare (3–5 per 1000 proximal femur fractures) and difficult to treat. Lack of standardised guidelines leads to a variability in fixation constructs, use of bone grafting and restricted weight bearing protocols, which are not evidence based. We hypothesised that there is no change in union rates without the use of bone grafting and immediate weight bearing post-operatively does not lead to increased complications.

The purpose of this study is to assess the long term results of combined ACL reconstruction and unicompartmental knee replacements (UKR). These patients have been selected for this combined operation due to their combination of instability symptoms from an absent ACL and unicompartmental arthritis.

Retrospective review of 44 combined UKR and ACL reconstruction by a single surgeon. Surgeries included both medial and lateral UKR combined with either revision ACL reconstruction or primary ACL reconstruction. Patient reported outcomes were obtained preoperatively, at one year, 5 years and 10 years. Revision rate was followed up over 13 years for a mean of 7.4 years post-surgery.

The average Oxford score at one year was 43 with an average increase from pre-operation to 1 year post operation of 15. For the 7 patients with 10 year follow up average oxford score was 42 at 1 year, 43 at 5 years and 45 at 10 years.

There were 5 reoperations. 2 for revision to total knee arthroplasty and 1 for an exchange of bearing due to wear. The other 2 were the addition of another UKR. For those requiring reoperation the average time was 8 years.

Younger more active patients presenting with ACL deficiency causing instability and unicompartmental arthritis are a difficult group to manage. Combining UKR and ACL reconstruction has scant evidence in regard to long term follow up but is a viable option for this select group. This paper has one of the largest cohorts with a reasonable follow up averaging 7.4 years and a revision rate of 11 percent.

Combined unilateral knee replacements and ACL reconstruction can be a successful operation for patients with ACL rupture causing instability and unicompartmental arthritis.

Abstract

Approximately 20% of primary and revision Total Knee Arthroplasty (TKA) patients require multiple revisions, which are associated with poor survivorship, with worsening outcomes for subsequent revisions. For revision surgery, either endoprosthetic replacements or metaphyseal sleeves can be used for the repair, however, in cases of severe defects that are deemed “too severe” for reconstruction, endoprosthetic replacement of the affected area is recommended. However, endoprosthetic replacements have been associated with high complication rates (high incidence rates of prosthetic joint infection), while metaphyseal sleeves have a more acceptable complication profile and are therefore preferred. Despite this, no guidance exists as to the maximal limit of bone loss, which is acceptable for the use of metaphyseal sleeves to ensure sufficient axial and rotational stability. Therefore, this study assessed the effect of increasing bone loss on the primary stability of the metaphyseal sleeve in the proximal tibia to determine the maximal bone loss that retains axial and rotational stability comparable to a no defect control.

Aim

Diagnosis of periprosthetic shoulder infections (PSI) is difficult as they are mostly caused by low-virulent bacteria and patients do not show typical infection signs, such as elevated blood markers, wound leakage, or red and swollen skin. Ultrasound-guided biopsies for culture may therefore be an alternative for mini-open biopsies as less costly and invasive method. The aim of this study was to determine the diagnostic value and reliability of ultrasound-guided biopsies for cultures alone and in combination polymerase chain reaction (PCR), and/or synovial markers for preoperative diagnosis of PSI in patients undergoing revision shoulder surgery.

Introduction

Angular deformities of the distal femur can be corrected by opening, closing and neutral wedge techniques. Opening wedge (OW) and closing wedge (CW) are popular and well described in the literature. CW and OW techniques lead to leg length difference whereas the advantage of neutral wedge (NW) technique has several unique advantages. NW technique maintains limb length, wedge taken from the closing side is utilised on the opening side and since the angular correction is only half of the measured wedge on either side, translation of distal fragment is minimum. Leg lengths are not altered with this technique hence a useful technique in large deformities. We found no reports of clinical outcomes using NW technique. We present a technique of performing external fixator assisted NW correction of large valgus and varus deformities of distal femur and dual plating and discuss the results.

Abstract

Obesity is a common in individuals undergoing arthroplasty, and the potential for weight loss with improved mobility may be expected by some. The aim of this study was 1. determine the proportion that achieved weight loss after hip or knee arthroplasty, and 2. examine the effect of obesity on patient reported outcomes (PROMS) and satisfaction with surgery.

Participants underwent primary TKA or THA between July 2015 and December 2020 and consented to participation in a research database with baseline PROMS, including weight, BMI, Oxford Knee, or Hip Score, and EQ5D. Participants repeated PROMS at 12 months after surgery with additional questions regarding satisfaction with surgery.

3449 patients completed PROMS 1 year after arthroplasty with weight and BMI. There were 1810 THA and 1639 TKA procedures. The mean baseline BMI was higher in TKA (29.8, SD 5.2) compared to THA (27.7, SD 5.0), p=0.001. A higher proportion of TKA were classified as obese class 1 (29% TKA, 19% THA), obese class 2 (11% TKA and 6% THA), and obese class 3 (5% TKA and 2% THA), p=0.001. The mean weight loss after 1 year was 0.4kg and 0.9kg in obese THA subjects and TKA subjects respectively. In the obese >5kg weight loss was achieved in 13% of TKA and 7% of THA (p=0.001). Obese experienced equivalent improvement in Oxford scores, compared to non-obese subjects. Satisfaction with surgery was reported by 95% of THA and 91% of TKA subjects with no significant differences between BMI group grades (p=0.491 THA and p=0.473 TKA).

Preoperative obesity was observed in 44% of TKA and 27% of THA subjects. In the obese only 1 in 10 subjects lost 5kg or more over 12 months. Obese patients experienced equivalent improvements in outcome after arthroplasty and rates of satisfaction with surgery to the non-obese.

Glutamate regulates the expression of apoptosis-related genes and triggers the apoptosis of fibroblasts in rotator cuff tendons. Subacromial bursitis is always accompanied by symptomatic rotator cuff tear (RCT). However, no study has been reported on the presence of glutamate in subacromial bursa and on its involvement of shoulder pain in patients who had RCT. The purposes of this study were to determine whether the glutamate expression in subacromial bursa is associated with the presence of RCT and with the severity of shoulder pain accompanying RCT.

Subacromial bursal tissues were harvested from patients who underwent arthroscopic rotator cuff tendon repair or glenoid labral repair with intact rotator cuff tendon. Glutamate tissue concentrations were measured, using a glutamate assay kit. Expressions of glutamate and its receptors in subacromial bursae were histologically determined. The sizes of RCT were determined by arthroscopic findings, using the DeOrio and Cofield classification. The severity of shoulder pain was determined, using visual analog scale (VAS). Any associations between glutamate concentrations and the size of RCT were evaluated, using logistic regression analysis. The correlation between glutamate concentrations and the severity of pain was determined, using the Pearson correlation coefficient. Differences with a probability <0.05 were considered statistically significant.

Glutamate concentrations showed significant differences between the torn tendon group and the intact tendon group (P = 0.009). Concentrations of glutamate significantly increased according to increases in tear size (P < 0.001). In histological studies, the expressions of glutamate and of its ionotropic and metabotropic receptors have been confirmed in subacromial bursa. Glutamate concentrations were significantly correlated with pain on VAS (Rho=0.56 and P =0.01).

The expression of glutamate in subacromial bursa is significantly associated with the presence of RCT and significantly correlated with its accompanying shoulder pain.

Acknowledgements: This research was supported by the Basic Science Research Program, through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2015R1D1A3A01018955 and 2017R1D1A1B03035232).

ZrN-multilayer coating is clinically well established in total knee arthroplasty [1–3] and has demonstrated significant reduction in polyethylene wear and metal ion release [4,5].

The goal of our study was to analyze the biotribological behaviour of the ZrN-multilayer coating on a polished cobalt-chromium cemented hip stem.

CoCr28Mo6 alloy hip stems with ZrN-multilayer coating (CoreHip®AS) were tested versus an un-coated version. In a worst-case-scenario the stems with ceramic heads have been tested in bovine serum in a severe cement interface debonding condition under a cyclic load of 3,875 N for 15 million cycles. After 1, 3, 5, 10 & 15 million cycles the surface texture was analysed by scanning-electron-microscopy (SEM) and energy-dispersive x-ray (EDX). Metal ion concentration of Co,Cr,Mo was measured by inductively coupled plasma mass spectroscopy (ICP-MS) after each test interval.

Based on SEM/EDX analysis, it has been demonstrated that the ZrN-multilayer coating keeps his integrity over 15 million cycles of severe stem cemented interface debonding without any exposure of the CoCr28Mo6 substrate.

The ZrN-multilayer coated polished cobalt-chromium cemented hip stem has shown a reduction of Co & Cr metal ion release by two orders of a magnitude, even under severe stem debonding and high interface micro-motion conditions.

ZrN-multilayer coating on polished cobalt-chromium cemented hip stems might be a suitable option for further minimisation of Co & Cr metal ion release in total hip arthroplasty. Clinical evidence has to be proven during the next years.

An increased number of neutrophils (NEUs) has long been associated with infections in the knee joints; their contribution to knee osteoarthritis (KOA) pathophysiology remains largely unexplored. This study aimed to compare the phenotypic and functional characteristics of synovial fluid (SF)-derived NEUs in KOA and knee infection (INF).

Flow cytometric analysis, protein level measurements (ELISA), NEU oxidative burst assays, detection of NEU phagocytosis (pHrodo^TM Green Zymosan Biparticles^TM Conjugate for Phagocytosis), morphological analysis of the SF-derived/synovial tissue NEUs, and cultivation of human umbilical vein endothelial cells (HUVECs) using SF supernatant were used to characterise NEUs functionally/morphologically.

Results: Compared with INF NEUs, KOA NEUs were characterised by a lower expression of CD11b, CD54 and CD64, a higher expression of CD62L, TLR2 and TLR4, and lower production of inflammatory mediators and proteases, except CCL2.

Functionally, KOA NEUs displayed an increased production of radical oxygen species and phagocytic activity compared with INF NEUs. Morphologically, KOA and INF cells displayed different cell sizes and morphology, histological characteristics of the surrounding synovial tissues and influence on endothelial cells. KOA NEUs were further subdivided into two groups: SF containing <10% and SF with 10%–60% of NEUs. Analyses of two KOA NEU subgroups revealed that NEUs with SF <10% were characterised by 1) higher CD54, CD64, TLR2 and TLR4 expression on their surface; 2) higher concentrations of TNF-α, sTREM-1, VILIP-1, IL-1RA and MMP-9 in SFs.

Our findings reveal a key role for NEUs in the pathophysiology of KOA, indicating that these cells are morphologically and functionally different from INF NEUs. Further studies should explore the mechanisms that contribute to the increased number of NEUs and their crosstalk with other immune cells in KOA.

This study was supported by the Ministry of Health of the Czech Republic (NU20-06-00269; NU21-06-00370).

Osteoarthritis, the most common degenerative joint disease, significantly impairs life quality and labor capability of patients. Synovial inflammation, initiated by HMGB1 (High mobility group box 1)-induced activation of macrophage, precedes other pathological changes. As an upstream regulator of NF-κB (nuclear factor-kappa B) and MAPK (mitogen-activated protein kinase) signaling pathway, TAK1 (TGF-β activated kinase 1) participates in macrophage activation, while its function in osteoarthritis remains unveiled. This study aims to investigate the role of TAK1 in the pathogenesis of osteoarthritis via both in vitro and in vivo approaches.

We performed immunohistochemical staining for TAK1 in synovial tissue, both in osteoarthritis patients and healthy control. Besides, immunofluorescence staining for F4/80 as macrophage marker and TAK1 were conducted as well. TAK1 expression was examined in RAW264.7 macrophages stimulated by HMGB1 via qPCR (Quantitative polymerase chain reaction) and Western blotting, and the effect of TAK1 inhibitor (5z-7 oxozeaenol) on TNF-α production was evaluated by immunofluorescence staining. Further, we explored the influence of intra-articular shRNA (short hairpin RNA) targeting TAK1 on collagenase-induced osteoarthritis in mice.

Immunohistochemical staining confirmed significant elevation of TAK1 in osteoarthritic synovium, and immunofluorescence staining suggested macrophages as predominant residence of TAK1. In HMGB1-stimulated RAW264.7 macrophages, TAK1 expression was up-regulated both in mRNA and protein level. Besides, TAK1 inhibitor significantly impairs the production of TNF-α by macrophages upon HMGB1 stimulation. Moreover, intra-articular injection of lentivirus loaded with shRNA targeting TAK1 (sh-TAK1) reduced peri-articular osteophyte formation in collagenase-induced osteoarthritis in mice.

TAK1 exerts a potent role in the pathogenesis of osteoarthritis by mediating the activation of macrophages.

Energy storing tendons such as the human Achilles and equine superficial digital flexor tendon (SDFT) are prone to age-related injury. Tendons have poor healing capacity and a lack of effective treatments can lead to ongoing pain, reduced function and re-injury. It is therefore important to identify the mechanisms underpinning age-related tendinous changes in order to develop more effective treatments. Our recent single cell sequencing data has shown that tendon cell populations have extensive heterogeneity and cells housed in the tendon interfascicular matrix (IFM) are preferentially affected by ageing. There is, however, a lack of established surface markers for cell populations in tendon, limiting the capacity to isolate distinct cell populations and study their contribution to age-related tendon degeneration. Here, we investigate the presence of the cell surface proteins MET proto-oncogene (MET), integrin subunit alpha 10 (ITGA10), fibroblast activation protein alpha (FAP) and platelet derived growth factor receptor alpha (PDGFRA) in the equine SDFT cell populations and their co-localisation with known markers.

Using Western blot we validated the specificity of selected antibodies in equine tissue before performing immunohistochemistry to establish the location of the respective proteins in the SDFT. We subsequently used double labelling immunofluorescence with the established mural cell marker desmin (DES) to distinguish between tenocyte and mural cell populations.

In situ, MET, ITGA10, and FAP presence was found in cells throughout the tendon whereas PDGFRA was present in cells within the IFM. Double labelling immunofluorescence with the mural cell marker DES showed lack of co-localisation between PDGFRA and DES suggesting PDGFRA is labelling an IFM cell population distinct from those associated with blood vessels.

PDGFRA is a promising target for the specific cell sorting of IFM-localised tenocytes, enabling their isolation and subsequent characterisation.

Acknowledgments: The authors acknowledge the Biotechnology and Biological Sciences Research Council (BB/W007282/1) for funding this work.

Occlusal loading and muscle forces during mastication aids in assessment of dental restorations and implants and jaw implant design; however, three-dimensional bite forces cannot be measured with conventional transducers, which obstruct the native occlusion. The aim of this study was to combine accurate jaw kinematics measurements, together with subject-specific computational modelling, to estimate subject-specific occlusal loading and muscle forces during mastication.

Motion experiments were performed on one male participant (age: 39yrs, weight: 82kg) with healthy dentition. Two low-profile magnetic sensors were fixed to the participant's teeth and the two dental arches digitised using an intra-oral scanner. The participant performed ten continuous of chewing on a polyurethane rubber sample of known material properties, followed by maximal compression (clenching). This was repeated at the molars, premolars of both the left and right sides, and central incisors. Jaw motion was simultaneously recorded from the sensors, and finite element modelling used to estimate bite force. Specifically, simulations of chewing and biting were performed by driving the model using the measured kinematics, and bite force magnitude and direction quantified. Muscle forces were then evaluated using a rigid-body musculoskeletal model of the patient's jaw.

The first molars generated the largest bite forces during chewing (left: 309 N, right: 311 N) and maximum-force biting (left: 496 N, right: 495 N). The incisors generated the smallest bite forces during chewing (75 N) and maximum-force biting (114 N). The anterior temporalis and superficial masseter muscles had the largest contribution to maximum bite force, followed by the posterior temporalis and medial pterygoid muscles.

This study presents a new method for estimating dynamic occlusal loading and muscle forces during mastication. These techniques provide new knowledge of jaw biomechanics, including muscle and occlusal loading, which will be useful in surgical planning and jaw implant design.

Intramedullary nails (IMNs) are the current gold standard for treatment of long bone diaphyseal and selected metaphyseal fractures. Their design has undergone many revisions to improve fixation techniques, conform to the bone shape with appropriate anatomic fit, reduce operative time and radiation exposure, and extend the indication of the same implant for treatment of different fracture types with minimal soft tissue irritation.

The IMNs are made or either titanium alloy or stainless steel and work as load-sharing internal splints along the long bone, usually accommodating locking elements – screws and blades, often featuring angular stability and offering different configurations for multiplanar fixation – to secure secondary fracture healing with callus formation in a relative-stability environment. Bone cement augmentation of the locking elements can modulate the construct stiffness, increase the surface area at the bone-implant interface, and prevent cut-through of the locking elements.

The functional requirements of IMNs are related to maintaining fracture reduction in terms of length, alignment and rotation to enhance fracture healing. The load distribution during patient's activities is along the entire bone-nail interface, with nail length and anatomic fit being important factors to avoid stress risers.

Stratification is required to ensure that only those patients likely to benefit, receive Autologous Chondrocyte Implantation (ACI); ideally by assessing a biomarker in the blood. This study aimed to assess differences in the plasma proteome of individuals who respond well or poorly to ACI.

Isobaric tag for relative and absolute quantitation (ITRAQ) mass spectrometry and label-free proteomics analyses were performed in tandem as described previously by our group (Hulme et al., 2017; 2018; 2021) using plasma collected from ACI responders (n=10) compared with non-responders (n=10) at each stage of surgery (Stage I, cartilage harvest and Stage II, cell implantation).

iTRAQ using pooled plasma detected 16 proteins that were differentially abundant at baseline in ACI responders compared with non-responders (n=10) (≥±2.0 fold; p<0.05). Responders demonstrated a mean Lysholm (patient reported functional score from 0–100) improvement of 33±13 and non-responders a mean worsening of −13±13 points. The most pronounced plasma proteome shift was seen in response to Stage I surgery in ACI non-responders, with 48 proteins being differentially abundant between the two surgical procedures. We have previously noted this marked shift in response to initial surgery in the SF of ACI non-responders, several of these proteins were associated with the Acute Phase Response. One of these proteins, clusterin, could be confirmed in patients’ plasma using an independent immunoassay using individual samples. Label-free proteomic data from individual samples identified only cartilage acidic protein-1 (known to associate with osteoarthritis progression) to be significantly more abundant at Stage I in the plasma of non-responders.

This study indicates that proteins can be identified within the plasma that have potential use in ACI patient stratification. Further work is required to validate the findings of this discovery-phase work in larger ACI cohorts.

Periprosthetic joint infections (PJI) are one of the most common reasons for orthopedic revision surgeries. In previous studies, it has been shown that silver modification of titanium (Ti-6Al-4V) surfaces by PMEDM (powder mixed electrical discharge machining) has an antibacterial effect on Staphylococcus aureus adhesion. Whether this method also influences the proliferation of bacteria has not been investigated so far. Furthermore, the effect is only limitedly investigated on the ossification processes. Therefore, the aim of this work is to investigate the antibacterial effect as well as the in vitro ossification process of PMEDM machined surfaces modified by integration of silver.

In this study, we analyzed adhesion and proliferation of S. aureus in comparison to of surface roughness, silver content and layer thickness of the silver-integrated-PMEDM surfaces (N = 5). To test the in vitro ossification, human osteoblasts (SaOs-2) and osteoclasts (differentiated from murine-bone-marrow-macrophages) were cultured on the silver surfaces (N = 3).

We showed that the attachment of S. aureus on the surfaces was significantly lower than on the comparative control surfaces of pure Ti-6Al-4V without incorporated silver, independently of the measured surface properties. Bacterial proliferation, however, was not affected by the silver content. No influence on the in vitro ossification was observed, whereas osteoclast formation was drastically reduced on the silver-modified surfaces.

We showed that 1 to 3% of silver in the surface layer significantly reduced the adhesion of S. aureus, but not the proliferation of already attached bacteria. At the same time, no influence on the in vitro ossification was observed, while no osteoclasts were formed on the surface. Therefore, we state that PMEDM with simultaneous silver modification of the machined surfaces represents a promising technology for endoprostheses manufacturing to reduce infections while at the same time optimizing bone ingrowth.

Treatment of posterior malleolar (PM) ankle fractures remain controversial. Despite increasing recommendation for small PM fragment fixation, high quality evidence demonstrating improved clinical outcomes over the unfixated PM is limited. We describe the medium-to-long term clinical and radiographical outcomes in younger adult patients with PM ankle fractures managed without PM fragment fixation.

A retrospective cohort study of patients aged 18-55 years old admitted under our orthopaedic unit between 1st of April 2009 and 31st of October 2013 with PM ankle fractures was performed. Inclusion criteria were that all patients must mobilise independently pre-trauma, have no pre-existing ankle pathologies, and had satisfactory bimalleolar and syndesmotic stabilisation. Open fractures, talar fractures, calcaneal fractures, pilon fractures, subsequent re-injury and major complications were excluded. All PM fragments were unfixated. Clinical outcomes were evaluated using Foot and Ankle Ability Measure (FAAM) with activities of daily living (ADL) and sports subscale, visual analogue scale (VAS) and patient satisfaction ratings. Osteoarthrosis was assessed using modified Kellgren-Lawrence scale on updated weightbearing ankle radiographs.

61 participants were included. Mean follow-up was 10.26 years. Average PM size was 16.19±7.39%. All participants were evaluated for clinical outcomes, demonstrating good functional outcomes (FAAM-ADL 95.48±7.13; FAAM-Sports 86.39±15.52) and patient satisfaction (86.16±14.42%), with minimal pain (VAS 1.13±1.65). Radiographical outcomes were evaluated in 52 participants, showing no-to-minimal osteoarthrosis in 36/52 (69.23%), mild osteoarthrosis in 14/52 (26.92%) and moderate osteoarthrosis in 2/52 (3.85%). Clinical outcomes were not associated with PM fragment size, post-reduction step-off, dislocation, malleoli fractured or syndesmotic injury. PM step-off and dislocation were associated with worse radiographical osteoarthrosis. Other published medium-to-long term studies reported overall good outcomes, with no differences after small fragment fixation.

The unfixated smaller posterior malleolus fragment demonstrated overall satisfactory clinical and radiographical outcomes at 10-year follow-up and may be considered a valid treatment strategy.

Anterior approach total hip arthroplasty (AA-THA) has a steep learning curve, with higher complication rates in initial cases. Proper surgical case selection during the learning curve can reduce early risk. This study aims to identify patient and radiographic factors associated with AA-THA difficulty using Machine Learning (ML).

Consecutive primary AA-THA patients from two centres, operated by two expert surgeons, were enrolled (excluding patients with prior hip surgery and first 100 cases per surgeon). K- means prototype clustering – an unsupervised ML algorithm – was used with two variables - operative duration and surgical complications within 6 weeks - to cluster operations into difficult or standard groups.

Radiographic measurements (neck shaft angle, offset, LCEA, inter-teardrop distance, Tonnis grade) were measured by two independent observers. These factors, alongside patient factors (BMI, age, sex, laterality) were employed in a multivariate logistic regression analysis and used for k-means clustering. Significant continuous variables were investigated for predictive accuracy using Receiver Operator Characteristics (ROC).

Out of 328 THAs analyzed, 130 (40%) were classified as difficult and 198 (60%) as standard. Difficult group had a mean operative time of 106mins (range 99–116) with 2 complications, while standard group had a mean operative time of 77mins (range 69–86) with 0 complications. Decreasing inter-teardrop distance (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.95–0.99, p = 0.03) and right-sided operations (OR 1.73, 95% CI 1.10–2.72, p = 0.02) were associated with operative difficulty. However, ROC analysis showed poor predictive accuracy for these factors alone, with area under the curve of 0.56. Inter-observer reliability was reported as excellent (ICC >0.7).

Right-sided hips (for right-hand dominant surgeons) and decreasing inter-teardrop distance were associated with case difficulty in AA-THA. These data could guide case selection during the learning phase. A larger dataset with more complications may reveal further factors.

Adult Spine Deformity (ASD) is a degenerative condition of the adult spine leading to altered spine curvatures and mechanical balance. Computational approaches, like Finite Element (FE) Models have been proposed to explore the etiology or the treatment of ASD, through biomechanical simulations. However, while the personalization of the models is a cornerstone, personalized FE models are cumbersome to generate. To cover this need, we share a virtual cohort of 16807 thoracolumbar spine FE models with different spine morphologies, presented in an online user-interface platform (SpineView). To generate these models, EOS images are used, and 3D surface spine models are reconstructed. Then, a Statistical Shape Model (SSM), is built, to further adapt a FE structured mesh template for both the bone and the soft tissues of the spine, through mesh morphing. Eventually, the SSM deformation fields allow the personalization of the mean structured FE model, leading to generate FE meshes of thoracolumbar spines with different morphologies. Models can be selectively viewed and downloaded through SpineView, according to personalized user requests of specific morphologies characterized by the geometrical parameters: Pelvic Incidence; Pelvic Tilt; Sacral Slope; Lumbar Lordosis; Global Tilt; Cobb Angle; and GAP score. Data quality is assessed using visual aids, correlation analyses, heatmaps, network graphs, Anova and t-tests, and kernel density plots to compare spinopelvic parameter distributions and identify similarities and differences. Mesh quality and ranges of motion have been assessed to evaluate the quality of the FE models. This functional repository is unique to generate virtual patient cohorts in ASD.

Acknowledgements: European Commission (MSCA-TN-ETN-2020-Disc4All-955735, ERC-2021-CoG-O-Health-101044828)

There is an evolving body of evidence that demonstrates the role of epigenetic mechanisms, such as DNA-methylation in the pathogenesis of OA. This systematic review aims to summarize the current evidence of DNA methylation and its influence on the pathogenesis of OA.

A pre-defined protocol in alignment with the PRISMA guidelines was employed to systematically review eight bibliographic databases, to identify associations between DNA-methylation of articular chondrocytes and osteoarthritis. A search of Medline (Ovid), Embase, Web-of-Science, Scopus, PubMed, Cinahl (EBSCOhost), Cochrane Central and Google Scholar was performed between 1st January 2015 to 31st January 2021. Data extraction was performed by two independent reviewers.

During the observation period, we identified 15 gene specific studies and 24 genome wide methylation analyses. The gene specific studies mostly focused on the expression of pro-inflammatory markers, such as IL8 and MMP13 which are overexpressed in OA chondrocytes. DNA hypomethylation in the promoter region resulted in overexpression, whereas hypermethylation was seen in non-OA chondrocytes. Others reported on the association between OA risk genes and the DNA methylation pattern close to RUNX2, which is an important OA signal. The genome wide methylation studies reported mostly on differentially methylated regions comparing OA chondrocytes and non-OA chondrocytes. Clustering of the regions identified genes that are involved in skeletal morphogenesis and development. Differentially methylated regions were seen in hip OA and knee OA chondrocytes, and even within different regions of an OA affected knee joint, differentially methylated regions were identified depending on the disease stage.

This systematic review demonstrates the growing evidence of epigenetic mechanisms, such as DNA methylation, in the pathogenesis of OA. In recent years, there has been a focus on the interplay between OA risk genes and DNA methylation changes which revealed a reactivation of genes responsible for endochondral ossification during development. These are important findings and may help to identify eventual future therapeutic targets. However, the current body of literature is mostly showing the differences in DNA methylation of OA chondrocytes and non-OA chondrocytes, but a true longitudinal analysis demonstrating the DNA methylation changes actually happening is still not available.

While high-performance ceramics like alumina and zirconia exhibit excellent wear resistance, they provide poor osseointegration capacity. As osseointegration is crucial for non-cemented joint prostheses, new techniques have been successfully developed for biofunctionalizing high-performance ceramic surfaces. Stable cell adhesion can be achieved by covalently bound specific peptides. In this study we investigate the effect of sterilization processes on organo-chemically functionalized surfaces.

To enhance the performance of alumina-toughened zirconia ceramics (ATZ), a 3-aminopropyldiisopropylethoxysilane (APDS) monolayer was applied and coupled with cyclo-RGD peptides (cRGD) by using bifunctional crosslinker bis(sulfosuccinimidyl)suberat (BS³). The samples were sterilized using e-beam or gamma-sterilization at 25 kGy, either before or after biofunctionalization with cRGD. Functionalization stability was investigated by contact angle measurements. The functionality of cRGD after sterilization was demonstrated using proliferation tests and cytotoxicity assays. Immunofluorescence staining (pFAK, Actin, DAPI) was conducted to evaluate the adhesion potential between the samples and human mesenchymal stem cells (hMSCs).

Functionalized samples before and after sterilization showed no significant difference regarding their contact angles. A proliferation test demonstrated that the cells on functionalized samples proliferate significantly more than on untreated samples before and after sterilization. hMSCs showed a significant higher proliferation on gamma sterilized samples compared to all other groups after 14 days. It was confirmed that the samples did not exhibit cytotoxic behavior before or after sterilization. Fluorescence microscopy demonstrated that both, cells on sterilized and on non-sterilized samples, expressed high levels of pFAK-Y397.

The investigated functionalization enables improved adhesion and proliferation of hMSCs and is stable against the investigated sterilization processes. This is of importance as the option of having a sterile product enables the start of the translation of this biofunctional coating towards preclinical and subsequently first-in-man applications.

Acknowledgments: We acknowledge the financial support of the Federal Ministry of Education and Research, BMBF (13GW0452A-C).

Contemporary indications for unicompartmental knee replacement (UKR) include bone on bone radiographic changes in the medial compartment with relatively preserved lateral and patellofemoral compartments. The role of MRI in identifying candidates for UKR is commonplace. The aim of this study was to assess the relationship between radiographic and MRI pre-operative grade and outcome following UKR.

A retrospective analysis of medial UKR patients from 2017 to 2021. Inclusion criteria were medial UKR for osteoarthritis with pre-operative and post-operative Oxford Knee Scores (OKS), pre-operative radiographs and MRI.

89 patients were included. Whilst all patients had grade 4 ICRS scores on MRI, 36/89 patients had grade 3 KL radiographic scores in the medial compartment, 50/89 had grade 4 KL scores on the medial compartment. Grade 3 KL with grade 4 IRCS medial compartment patients had a mean OKS change of 17.22 (Sd 9.190) meanwhile Grade 4 KL had a mean change of 17.54 (SD 9.001), with no statistical difference in the OKS change score following UKR between these two groups (p=0.873). Medial bone oedema was present in all but one patient. Whilst lateral compartment MRI ICRS scores ranged from 1 to 4 there was no association with MRI score of the lateral compartment and subsequent change in oxford score (P value 0.458). Patellofemoral Compartment (PFC) MRI ICRS ranged from 0 to 4. There was no association between PFC ICRS score and subsequent change in oxford knee score (P value .276)

Radiographs may under report severity of some medial sided knee osteoarthritis. We conclude that in patients with grade 3 KL score that would normally not be considered for UKR, pre-operative MRI might identify grade 4 ICRS scores and this subset of patients have equivalent outcomes to patients with radiographic Grade 4 KL medial compartment osteoarthritis.

Osteoarthritis (OA) of the knee joint is a complex peripheral joint disorder with multiple risk factors. We aimed to examine the relationship between the grade of knee OA and anterior thigh length (ATL).

A total of 64 geriatric patients who had no total hip or knee replacement with a BMI of ≥30 were evaluated. Patients' OA severity was determined by two independent experts from bilateral standing knee radiographs according to the Kellgren-Lawrence (KL) grade. Joint cartilage structure was assessed using ultrasonography (US). The ATL, the gastrocnemius medialis (GC), the rectus femoris (RF) and the rectus abdominis (RA) skeletal muscle thicknesses as well as the RF cross-sectional area (CSA) were measured with US. Sarcopenia was diagnosed using the handgrip strength (HGS), 5× sit-to-stand test (5xSST) and bioelectrical impedance analysis.

The median (IQR) age of participants was 72 (65–88) years. Seventy-one per cent of the patients (n=46) were female. They were divided into the sarcopenic obese (31.3 %) and the non-sarcopenic obese (68.8%) groups. KL grade of all patients correlated negatively with the ATL (mm) and the thickness of GC (mm) (r= -0,517, p<0.001 and r= -0.456, p<0.001, respectively). In the sarcopenic obese and the non-sarcopenic obese groups, KL grade of the all patients was negatively correlated with ATL (mm) and thickness of GC (mm) (r= -0,986, p<0.001; r= -0.456, p=0.05 and r= -0,812, p=0.002; r= −0,427, p=0.006). KL grade negatively correlated with the RF thickness in the sarcopenic obese group (r= -0,928, p=0.008).

In conclusion, OA risk may decrease as the lower extremity skeletal muscle mass increases.

Acknowledgments: Feza Korkusuz MD is a member of the Turkish Academy of Sciences (TÜBA).

The incisura fibularis (IF) provides intrinsic stability to the ankle joint complex by interlocking the distal tibia and fibula. Despite a high frequency of ligamentous ankle injuries, scant attention has been given to the morphology of the IF morphology incisura fibularis in the onset and development of these lesions. Therefore, we systematically reviewed the relation between ligamentous ankle disorders and the morphometrics of the IF.

A systematic literature search was conducted on following databases: PubMed, Embase and Web of Science. Search terms consisted of ‘ankle trauma’, ‘ankle injury’, ‘ankle sprain’, ‘ankle fracture’, ‘tibiofibular’, ‘fibular notch’, ‘fibular incisura’, ‘incisura fibularis’, ‘morphometric analysis’, ‘ankle syndesmosis’, ‘syndesmotic stability’. The evaluation instrument developed by Hawker et al. was used to assess the quality of the selected studies. This protocol was performed according to the PRISMA guidelines and is registered on PROSPERO (CRD42021282862).

Nineteen studies were included and consisted of prospective cohort (n=1), retrospective comparative (n=10), and observational (n=8) study design. Comparative studies have found certain morphological characteristics in patients with ankle instability. Several studies (n=5) have correlated a shallow IF depth with a higher incidence of ankle injury. A significant difference has also been found concerning the incisura height and angle (n=3): a shorter incisura and more obtuse angle have been noted in patients with ankle sprains. The mean Hawker score was 28 out of 36 (range=24-31).

A shallower IF is associated with ligamentous ankle lesions and might be due to a lower osseous resistance against tibiofibular displacement. However, these results should be interpreted in light of moderate methodological quality and should always be correlated with clinical findings. Further prospective studies are needed to further assess the relation between the incisura morphometrics and ligamentous disorders of the ankle joint.

Keywords: ankle instability, ankle injury, incisura fibularis, fibular notch, tibiofibular morphometrics, ankle syndesmosis

Knee osteoarthritis (KOA) diagnosis is based on symptoms, assessed through questionnaires such as the WOMAC. However, the inconsistency of pain recording and the discrepancy between joint phenotype and symptoms highlight the need for objective biomarkers in KOA diagnosis. To this end, we study relationships among clinical and molecular data in a cohort of women (n=51) with Kellgren-Lawrence grade 2–3 KOA through Support Vector Machine (SVM) and a regulation network model (RNM). Clinical descriptors (i.e., pain catastrophism (CA); depression (DE); functionality (FU); joint pain (JP); rigidity (RI); sensitization (SE); synovitis (SY)) are used to classify patients. A Youden's test is performed for each classifier to determine optimal binarization thresholds for the descriptors. Thresholds are tested against patient stratification according to baseline WOMAC data from the Osteoarthritis Initiative, and the mean accuracy is 0.97. For our cohort, the data used as SVM inputs are KOA descriptors, synovial fluid (SL) proteomic measurements (n=25), and transcription factors (TF) activation obtained from RNM [2] stimulated with the SL measurements. The relative weights after classification reflect input importance. The performance of each classifier is evaluated through AUC-ROC analysis. The best classifier with clinical data is CA (AUC = 0.9), highly influenced by FU and SE, suggesting that kinesophobia is involved in pain perception. With SL input, leptin strongly influences every classifier, suggesting the importance of low-grade inflammation. When TF are used, the mean AUC is limited to 0.608, which can be related to the pleomorphic behaviour of osteoarthritic chondrocytes. Nevertheless, FU has an AUC of 0.7 with strong importance of FOXO downregulation. Though larger and longitudinal cohorts are needed, this unique combination of SVM and RNM shall help to map objectively KOA descriptors.

Acknowledgements: Catalan & Spanish governments 2020FI_b00680; STRATO-PID2021126469ob-C21-2, European Commission (MSCA-TN-ETN-2020-Disc4All-955735, ERC-2021-CoG-O-Health-101044828). ICREA Academia.

Meniscus tears have been treated using partial meniscectomy to relieve pain in patients, although this leads to the onset of early osteoarthritis (OA). Cell-based therapies can help preserve the meniscus, although the presence of inflammatory cytokines compromises clinical outcomes. Anti-inflammatory drugs (e.g. celecoxib), can help to reduce pain in patients and in vitro studies suggest a beneficial effect on cytokine inhibited matrix content. Previously, we have demonstrated that the inhibitory effects of IL-1β can be countered by culture under low oxygen tension or physioxia. The present study sought to understand whether physioxia, celecoxib or combined application can counter the inhibitory effects IL-1β inhibited meniscus cells.

Human avascular and vascular meniscus cells (n =3) were isolated and expanded under 20% (hyperoxia) or 2% (physioxia) oxygen. Cells were seeded into collagen scaffolds (Geistlich, Wolhusen) and cultured for 28 days either in the presence of 0.1ng/mL IL-1β, 5µg/mL celecoxib or both under their expansion oxygen conditions. Histological (DMMB, collagen I and collagen II immunostaining), GAG content and gene expression analysis was evaluated for the scaffolds.

Under hyperoxia, meniscus cells showed a significant reduction in GAG content in the presence of IL-1β (*p < 0.05). Celecoxib alone did not significantly increase GAG content in IL-1β treated cultures. In contrast, physioxic culture showed a donor dependent increase in GAG content in control, IL-1β and celecoxib treated cultures with corresponding histological staining correlating with these results. Additionally, gene expression showed an upregulation in COL1A1, COL2A1 and ACAN and a downregulation in MMP13 and ADAMTS5 under physioxia for all experimental groups.

Physioxia alone had a stronger effect in countering the inhibitory effects of IL-1β treated meniscus cells than celecoxib under hyperoxia. Preconditioning meniscus cells under physioxia prior to implantation has the potential to improve clinical outcomes for cell-based therapies of the meniscus.