Introduction and Objective. Malunion after trauma can lead to coronal plane malalignment in the lower limb. The mechanical hypothesis suggests that this alters the load distribution in the knee joint and that that this increased load may predispose to compartmental arthritis. This is generally accepted in the orthopaedic community and serves as the basis guiding deformity correction after malunion as well as congenital or insidious onset malalignment. Much of the literature surrounding the contribution of lower limb alignment to arthritis comes from cohort studies of incident osteoarthritis. There has been a causation dilemma perpetuated in a number of studies - suggesting malalignment does not contribute to, but is instead a consequence of, compartmental arthritis. In this investigation the relationship between compartmental (medial or lateral) arthritis and coronal plane malalignment (varus or valgus) in patients with post traumatic unilateral limb deformity was examined. This represents a specific niche cohort of patients in which worsened compartmental knee arthritis after extra-articular injury must rationally be attributed to malalignment. Materials and Methods. The picture archiving system was searched to identify all 1160 long leg x ray films available at a major metropolitan trauma center over a 12-year period. Images were screened for inclusion and exclusion criteria, namely patients >10 years after traumatic long bone fracture without contralateral injury or arthroplasty to give 39 cases. Alignment was measured according to established surgical standards on long leg films by 3 independent reviewers, and arthritis scores Osteoarthritis Research Society International (OARSI) and Kellegren-Lawrence (KL) were recorded independently for each compartment of both knees. Malalignment was defined conservatively as mechanical axis deviation outside of 0–20 mm medial from centre of the knee, to give 27 patients. Comparison of mean compartmental arthritis score was performed for patients with varus and valgus malalignment, using Analysis of Variance and linear regression. Results. In knees with varus malalignment there was a greater mean arthritis score in the medial compartment compared to the contralateral knee, with OARSI scores 5.69 vs 3.86 (0.32, 3.35 95% CI; p<0.05) and KL 2.92 vs 1.92 (0.38, 1.62; p<0.005). There was a similar trend in valgus knees for the lateral compartment OARSI 2.98 vs 1.84 (CI −0.16, 2.42; p=0.1) and KL 1.76 vs 1.31 (CI −0.12, 1.01; p=0.17), but the evidence was not conclusive. OARSI arthritis score was significantly associated with absolute MAD (0.7/10mm MAD, p<0.0005) and Time (0.6/decade, p=0.01) in a linear regression model. Conclusions. Malalignment in the coronal plane is correlated with worsened arthritis scores in the medial compartment for varus deformity and may similarly result in worsened lateral compartment arthritis in valgus knees. These findings support the mechanical hypothesis that arthritis may be related to altered stress distribution at the knee, larger studies may provide further conclusive evidence

Acetabular morphology and orientation differs from ethnic group to another. Thus, investigating the natural history of the parameters that are used to assess both was a matter of essence. Nevertheless, clarification the picture of normal value in our society was the main aim of this study. However, Acetabular head index (AHI) and center edge angle (CEA) were the most sensitive indicative parameters for acetabular dysplasia. Hence, they were the main variables used in evaluation of acetabular development. A cross-sectional retrospective study that had been done in a tertiary center. Computed tomography abdomen scouts’ radiographs of non-orthopedics patients were included. They had no history of pelvic or hips’ related symptoms or fractures in femur or pelvis. Images’ reports were reviewed to exclude those with tumors in the femur or pelvic bones. A total of 81 patients was included with 51% of them were males. The mean of age was 10.38± 3.96. CEA was measured using Wiberg technique, means of CEA were 33.71±6.53 and 36.50±7.39 for males and females, respectively. Nonetheless, AHI means were 83.81±6.10 and 84.66±4.17 for males and females, respectively. On the other hand, CEA was increasing by a factor 0.26 for each year (3-18, range). In addition, positive significant correlation was detected between CEA and age as found by linear regression r 2 0.460 (f(df1,79) =21.232, P ≤0.0001). Also, Body mass index (BMI) was positively correlated with CEA r 0.410, P 0.004). This study shows that obesity and aging are linked to increased CEA. Each ethnic group has its own normal values that must be studied to avoid premature diagnosis

Femoroacetabular impingement (FAI) results from a morphological deformity of the hip and is associated with osteoarthritis (OA). Increased bone mineral density (BMD) is observed in the antero-superior acetabulum rim where impingement occurs. It is hypothesized that the repeated abnormal contact leads to damage of the cartilage layer, but could also cause a bone remodelling response according to Wolff's Law. Thus the goal of this study was to assess the relationship between bone metabolic activity measured by PET and BMD measured in CT scans. Five participants with asymptomatic cam deformity, three patients with uni-lateral symptomatic cam FAI and three healthy controls were scanned in a 3T PET-MRI scanner following injection with [18F]NaF. Bone remodelling activity was quantified with Standard Uptake Values (SUVs). SUVmax was analyzed in the antero-superior acetabular rim, femoral head and head-neck junction. In these same regions, BMD was calculated from CT scans using the calibration phantom included in the scan. The relationship between SUVmax and BMD from corresponding regions was assessed using the coefficient of determination (R. 2. ) from linear regression. High bone activity was seen in the cam deformity and acetabular rim. SUVmax was negatively correlated with BMD in the antero-superior region of the acetabulum (R. 2. =0.30, p=0.08). SUVmax was positively correlated with BMD in the antero-superior head-neck junction of the femur (R. 2. =0.359, p=0.067). Correlations were weak in other regions. Elevated bone turnover was seen in patients with a cam deformity but the relationship to BMD was moderate. This study demonstrates a pathomechanism of hip degeneration associated with FAI deformities, consistent with Wolff's law and the proposed mechanical cause of hip degeneration in FAI. [18F]-NaF PET SUV may be a biomarker of degeneration, especially in early stages of degeneration, when joint preservation surgery is likely to be the most successful

Abstract. Objectives. The ability to predict which patients will improve following routine surgeries aimed at preventing the progression of osteoarthritis is needed to aid patients being stratified to receive the most appropriate treatment. This study aimed to investigate the potential of a panel of biomarkers for predicting (prior to treatment) the clinical outcome following treatment with microfracture or osteotomy. Methods. Proteins known to relate to OA severity, with predictive value in autologous cell implantation treatment or that had been identified in proteomic analyses (aggrecanase-1/ ADAMTS-4, cartilage oligomeric matrix protein (COMP), hyaluronic acid (HA), Lymphatic Vessel Endothelial Hyaluronan Receptor-1, matrix metalloproteinases-1 and −3, soluble CD14, S100 calcium binding protein A13 and 14-3-3 protein theta) were assessed in the synovial fluid (SF) of 19 and 13 patients prior to microfracture or osteotomy, respectively, using commercial immunoassays. Levels of COMP and HA were measured in the plasma of these patients. To find predictors of postoperative function, multiple linear regression analyses were performed. Results. Linear regression analyses demonstrated that a lower concentration of HA in pre-operative SF was predictive of improved knee function (higher Lysholm score) following microfracture surgery. Further, lower pre-operative activity of ADAMTS-4 in SF was a significant, independent predictor of higher post-operative Lysholm score (improved joint function) following osteotomy surgery. Conclusion. This study is novel in identifying biomarkers with the potential to predict clinical outcome in patients treated with microfracture or osteotomy of the knee. Lower concentrations of HA and undetectable activity of ADAMTS-4 in the joint fluid of individuals with cartilage defects/early-OA may be used in algorithms to stratify patients to the most appropriate surgery. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

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

Mental disorders in particular depression and anxiety have been reported to be prevalent among patients with spinal pathologies. Goal of the current study was to analyze the relationship of Zung pre- and post-op score to other PROs and length of stay. Secondary outcomes included revision surgery and post-operative infections. Data from the international multicenter prospective spine degenerative surgery data repository, DegenPRO v1.1 (AO Spine Knowledge Forum Degenerative) were utilized. Patients undergoing cervical or lumbar procedure were included. Patient's demographics, Charlson Comorbidity Index, surgical information, Zung score, NDI, pain related PROs and EQ-5D, and complications at surgery and at various post-op time periods. Except for hospital duration, data were analyzed, using multivariable mixed linear models. A robust linear regression model was used to assess the association between Zung score and hospital duration. All models were adjusted for gender and age. 42 patients had Zung score administered. Among those patients 22 (52%) were within normal range, 18 (43%) were mildly and 2 (5%) severely depressed. 62% of the patients had a lumbar pathology with fusion procedures being the most common. Median EQ-5D (3L) score at surgery was significantly higher (0.7, IQR: 0.4-0.7) for patients within normal range than for those with mild (0.4, IGR: 0.3-0.7) or severe depression (0.3, IQR: 0.3-0.3, p-value: 0.05). Compared to patients within normal Zung range, mixed models, indicated lower EQ-5D (3L) score values and higher values for neck and arm pain at surgery with both PROs and EQ-5D (3L) improving in patients with depression over the follow-up time. No association was found between Zung score and hospital length of stay. The initial analysis showed that 43% of the patients were mildly depressed and mainly male patients. Zung score was correlated with post-operative improvements in EQ-5D and arm and neck pain PROs

Abstract. Objectives. Accurate orientation of the acetabular component during a total hip replacement is critical for optimising patient function, increasing the longevity of components, and reducing the risk of complications. This study aimed to determine the validity of a novel VR platform (AescularVR) in assessing acetabular component orientation in a simulated model used in surgical training. Methods. The AescularVR platform was developed using the HTC Vive® VR system hardware, including wireless trackers attached to the surgical instruments and pelvic sawbone. Following calibration, data on the relative position of both trackers are used to determine the acetabular cup orientation (version and inclination). The acetabular cup was manually implanted across a range of orientations representative of those expected intra-operatively. Simultaneous readings from the Vicon® optical motion capture system were used as the ‘gold standard’ for comparison. Correlation and agreement between these two methods was determined using Bland-Altman plots, Pearson's correlation co-efficient, and linear regression modelling. Results. A total of 55 separate orientation readings were obtained. The mean average difference in acetabular cup version and inclination between the Vicon and VR systems was 3.4° (95% CI: −3–9.9°), and −0.005° (95% CI: −4.5–4.5°) respectively. Strong positive correlations were demonstrated between the Vicon and VR systems in both acetabular cup version (Pearson's R = 0.92, 99% CI: 0.84–0.96, p<0.001), and inclination (Pearson's R = 0.94, 99% CI: 0.88–0.97, p<0.001). Using linear regression modelling, the adjusted R. 2. for acetabular version was 0.84, and 0.88 for acetabular inclination. Conclusion. The results of this study indicate that the AescularVR platform is highly accurate and reliable in determining acetabular component orientation in a simulated environment. The AescularVR platform is an adaptable tracking system, which may be modified for use in a range of simulated surgical training and educational purposes, particularly in orthopaedic surgery. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Abstract. Objectives. Develop a methodology to assess the long term mechanical behavior of intervertebral discs by utilizing novel sequential state testing. Methods. Bovine functional spinal units were sequentially mechanically tested in (1) native (n=8), (2) degenerated (n=4), and (3) treated states (n=4). At stage (2), artificial degeneration was created using rapid enzymatic degeneration, followed by a 24 hour hold period under static load at 42°C. At stage (3), nucleus augmentation treatments were injected with a hydrogel or a ‘sham’ (water, chondroitin sulfate) injection. The mechanical protocol employed applied a static load hold period followed by cyclic compressive loading between ∼350 and 750 N at 1 Hz. 1000 cycles were applied at each stage, and the final test on each specimen was extended up to 20000 cycles. To verify if test time can be reduced, functions were fitted using stiffness data up to 100, 1000, 2500, 5000, 10000 and 20000 cycles. Linear regression for the native specimens comparing the stiffness at various cycles to the stiffness at 20000 cycles was completed. Results. Independent of the disc state, as the number of cycles increased, the hysteresis decreased and the stiffness increased. The degenerated specimen stiffness was greater than the healthy and treated stiffness and the degenerate hysteresis loops were smaller. A mathematical model was found to successfully predict the high cycle behaviour of the disc reaching a root mean squared (RMS) error below 10% when using 5000 or more cycles. The linear regression gave a RMS error below 7.5% at 1000 cycles. Conclusions. A method was developed to consistently determine intervertebral disc mechanics through sequential testing. A shortened cyclic testing period was shown to be viable as a method to reduce preliminary test time for novel hydrogels, compared to currently literature. The methodology permits rapid preliminary assessment of intervertebral disc mechanics and treatments. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Bone metastases radiographically appear as regions with high (i.e. blastic metastases) or low (i.e. lytic metastases) bone mineral density. The clinical assessment of metastatic features is based on computed tomography (CT) but it is still unclear if the actual size of the metastases can be accurately detected from the CT images and if the microstructure in regions surrounding the metastases is altered (Nägele et al., 2004, Calc Tiss Int). This study aims to evaluate (i) the capability of the CT in evaluating the metastases size and (ii) if metastases affect the bone microstructure around them. Ten spine segments consisted of a vertebra with lytic or mixed metastases and an adjacent control (radiologically healthy) were obtained through an ethically approved donation program. The specimens were scanned with a clinical CT (AquilionOne, Toshiba: slice thickness:1mm, in-plane resolution:0.45mm) to assess clinical metastatic features and a micro-CT (VivaCT80, Scanco, isotropic voxel size:0.039mm) to evaluate the detailed microstructure. The volume of the metastases was measured from both CT and micro-CT images (Palanca et al., 2021, Bone) and compared with a linear regression. The microstructural alteration around the metastases was evaluated in the volume of interest (VOI) defined in the micro-CT images as the volume of the vertebral body excluding the metastases. Three 3D microstructural parameters were calculated in the VOI (CTAn, Bruker SkyScan): Bone Volume Fraction (BV/TV), Trabecular Thickness (Tb.Th.), Trabecular Spacing (Tb.Sp.). Medians of each parameter were compared (Kruskal-Wallis, p=0.05). One specimen was excluded as it was not possible to define the size of the metastases in the CT scans. A strong correlation between the volume obtained from the CT and micro-CT images was found (R2=0.91, Slope=0.97, Intercept=2.55, RMSE=5.7%, MaxError=13.12%). The differences in BV/TV, Tb.Th. and Tb.Sp. among vertebrae with lytic and mixed metastases and control vertebrae were not statistically significant (p-value>0.6). Similar median values of BV/TV were found in vertebrae with lytic (13.2±2.4%) and mixed (12.8±9.8%) metastases, and in controls (13.0±10.1%). The median Tb.Th. was 176±18 ∓m, 179±43 ∓m and 167±91 ∓m in vertebrae with lytic and mixed metastases and control vertebrae, respectively. The median Tb. Sp. was 846±26 ∓m, 849±286 ∓m and 880±116 ∓m in vertebrae with lytic and mixed metastases and control vertebrae, respectively. In conclusion, the size of vertebral metastases can be accurately assess using CT images. The 3D microstructural parameters measured were comparable with those reported in the literature for healthy vertebrae (Nägele et al., 2004, Calc Tiss Int, Sone et al., 2004, Bone) and showed how the microstructure of the bone tissue surrounding the lesion is not altered by the metastases

Abstract. Objectives. Spinal stiffness and flexibility terms are typically evaluated from linear regression of experimental data and are then assembled into 36-element matrices. Summarising in vitro test results in this manner is quick, computationally cheap and has the distinct advantage of outputting simple characteristic values which make it easy to compare results. However, this method disregards many important experimental features such as stiffening effects, neutral and elastic zones magnitudes, extent of asymmetry and energy dissipation (hysteresis). Alternatives to the linear least squares method include polynomials, separation of the load-displacement behaviour into the neutral and elastic zones using various deterministic methods and variations on the double sigmoid and Boltzmann curve fits. While all these methods have their advantages, none provide a comprehensive and complete characterisation of the load-displacement behaviour of spine specimens. In 1991, Panjabi demonstrated that the flexion-extension and mediolateral bending behaviour of functional spinal units could be approximated using the viscoelastic model consisting of a nonlinear spring in series with a linear Kelvin element. Nowadays viscoelastic models are mainly used to describe creep and stress relaxation, rather than for cyclic loading. The aim of this study was to conclusively prove the viscoelastic nature of spinal behaviour subject to cyclic loading. Being able to describe the behaviour of spine specimens using springs and dampers would yield characterising coefficients with recognisable physical meaning, thus providing an advantage over existing techniques. Methods. Six porcine isolated spinal disc specimens (ISDs) were tested under position and load control. Visual inspection of the load-displacement graphs from which the principal terms of the stiffness and flexibility matrices are derived suggest that the load-displacement behaviour could be idealised by a nonlinear spring system with damping. It was hypothesised that the contributions arising from non-linear spring-like behaviour and damping could be separated for each of the principal load-displacement graphs. Results. The principal elements from position and load control tests were plotted with load on the vertical axis and displacement on the horizontal axis, and a polynomial representing spring force was fitted to the data. This polynomial was subtracted from the experimental data. The remainder - representing damping force - was plotted against displacement and velocity and compared to idealised plots for different types of damping behaviour. Applying this reasoning to the six principal load-displacement plots obtained from stiffness and flexibility tests revealed that four of six exhibit behaviour which is a combination of a nonlinear hardening spring and viscous damper. However, for flexion-extension and mediolateral bending, the damping behaviour is more akin to coulomb damping with viscous influences, characterised by a steep central linear region and near horizontal regions at the extremes. These trends were common amongst all six specimens within the study sample size. Conclusions. The unique approach described here has allowed the characterisation of the load-displacement behaviour of ISDs in terms of characteristic mass-spring-damper systems. This is an important development which allows experimental findings to be framed in terms of mechanical contributions to a given load-displacement behaviour. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Mechanical failure of spine posterior fixation in the lumbar region Is suspected to occur more frequently when the sagittal balance is not properly restored. While failures at the proximal extremity have been studied in the literature, the lumbar distal junctional pathology has received less attention. The aim of this work was to investigate if the spinopelvic parameters, which characterize the sagittal balance, could predict the mechanical failure of the posterior fixation in the distal lumbar region. All the spine surgeries performed in 2017-2019 at Rizzoli Institute were retrospectively analysed to extract all cases of lumbar distal junctional pathology. All the revision surgeries performed due to the pedicle screws pull-out, or the breakage of rods or screws, or the vertebral fracture, or the degenerative disc disease, in the distal extremity, were included in the junctional (JUNCT) group. A total of 83 cases were identified as JUNCT group. All the 241 fixation surgeries which to date have not failed were included in the control (CONTROL) group. Clinical data were extracted from both groups, and the main spinopelvic parameters were assessed from sagittal standing preoperative (pre-op) and postoperative (post-op) radiographs with the software Surgimap (Nemaris). In particular, pelvic incidence (PI), sagittal vertical axis (SVA), pelvic tilt (PT), T1 pelvic angle (TPA), sacral slope (SS) and lumbar lordosis (LL) have been measured. In JUNCT, the main failure cause was the screws pull-out (45%). Spine fixation with 7 or more levels were the most common in JUNCT (52%) in contrast to CONTROL (14%). In CONTROL, PT, TPA, SS and PI-LL were inside the recommended ranges of good sagittal balance. For these parameters, statistically significant differences were observed between pre-op and post-op (p<0.0001, p=0.01, p<0.0001, p=0.004, respectively, Wilcoxon test). In JUNCT, the spinopelvic parameters were out of the ranges of the good sagittal balance and the worsening of the balance was confirmed by the increase in PT, TPA, SVA, PI-LL and by the decrease of LL (p=0.002, p=0.003, p<0.0001, p=0.001, p=0.001, respectively, paired t-test) before the revision surgery. TPA (p=0.003, Kolmogorov-Smirnov test) and SS (p=0.03, unpaired t-test) differed significantly in pre-op between JUNCT and CONTROL. In post-op, PI-LL was significantly different between JUNCT and CONTROL (p=0.04, unpaired t-test). The regression model of PT vs PI was significantly different between JUNCT and CONTROL in pre-op (p=0.01, Z-test). These results showed that failure is most common in long fused segments, likely due to long lever arms leading to implant failure. If the sagittal balance is not properly restored, after the surgery the balance is expected to worsen, eventually leading to failure: this effect was confirmed by the worsening of all the spinopelvic parameters before the revision surgery in JUNCT. Conversely, a good sagittal balance seems to avoid a revision surgery, as it is visible is CONTROL. The mismatch PI-LL after the fixation seems to confirm a good sagittal balance and predict a good correction. The linear regression of PT vs PI suggests that the spine deformity and pelvic conformation could be a predictor for the failure after a fixation

Introduction and Objective. Several factors contribute to the duration of the hospital stay in patients that undergo to total hip arthroplasty (THA), either subjective or perioperative. However, no definite evidence has been provided on the role of any of these factors on the hospitalization length. The aim of this retrospective investigation is to evaluate the correlation between several preoperative and perioperative factors and the length of hospital stay (LOS) in patients that underwent elective total hip arthroplasty. Materials and Methods. Medical records of patients that underwent THA since the beginning of 2016 to the end of 2018 were retrospectively screened. Demographics, comorbidities, renal function, whole blood count. and length of post-operative ward stay were retrieved. The association between clinical, biochemical and surgical factors and the length of hospital stay was explored by means of linear regression models. Results. A total of 743 subjects were included. Retrieved comorbidity included arterial hypertension (47%), dyslipidaemia (20%), chronic kidney disease (CKD) (12%) and diabetes mellitus (9%). The median length of post-operative hospital stay was 4 days (IQR: 2). Variables associated with linear increase of hospitalization length were the estimated Glomerular Filtration Rate (eGFR) (Beta −0.01, 95% CI −0.02, 0), CKD (Beta 0.82, 95% CI 0.29, 1.34), duration of surgery (Beta 0.69, 95% CI 0.44, 0.94). After correction for multiple confounders, the CKD (a-Beta 1.58 95%CI 0.00 – 3.22) and operation time (a-Beta 0.67, 95% CI 0.42, 0.92) were consistently associated with the outcome. Conclusions. Our analysis demonstrated a significant role played by the eGFR (as an index of renal function) in influencing the length of hospital stay

Abstract. Objectives. The objective of this study was to determine the kinematic factor(s) underlying the reduction in walking velocity displayed by total hip arthroplasty (THA) patients in comparison to healthy controls during walking gait. Methods. Eleven patients with well-functioning THA (71 ± 8 years, Oxford Hip Score = 46 ± 3) and ten healthy controls (61 ± 5 years) participated within this study. Sagittal plane lower limb kinematics were captured using a 10 camera Qualisys motion capture system, sampling at 200Hz, as participants walked overground at a self-selected pace. Bivariate linear regression was used to explore the relationship between walking velocity and a number of kinematic variables in a deterministic manner. Kinematic variables significantly associated with walking velocity were compared between THA and healthy groups utilising independent samples t-tests. Results. Peak hip extension was a significant (r2 = .36; p =.004) predictor of hip range of motion. Hip range of motion significantly (r. 2. = .61 p <.001) predicted stride length. Stride length was a significant (r2 = .75; p <.001) predictor of walking velocity. Peak hip extension and range of motion, and stride length were significantly (p ≤ .033) smaller for the THA group compared to the healthy control group. Conclusions. The deterministic model developed within this study links slower walking velocities to smaller peak hip extension, via reductions in hip range of motion and stride length. Stride length, hip range of motion and peak hip extension were all significantly lower for the THA group compared to the healthy group, despite patients reporting the implants to be well-functioning. Elucidating the mechanism(s) which restrict peak hip extension within THA populations is essential for maximising functional recovery and walking velocity post-operatively. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Abstract. Cranial cruciate ligament (CrCL) disease in dogs causes pain and osteoarthritis (OA) and surgical treatment does not prevent OA progression. Glutamate receptor (GluR) antagonists alleviate pain and degeneration in rodent models of OA, but it is unknown whether they are a suitable treatment for dogs. Understanding GluR signalling in CrCL disease may lead to novel therapeutics in both veterinary and human medicine. Objectives. To determine whether age, breed, sex, weight, and therapeutic(s) influence lameness and pre-operative radiographic OA scoring in dogs with CrCL disease and whether GluRs are expressed, in this disease. Methods. Surgical waste (CrCL and medial meniscus), clinical data, stifle radiographs, lameness scores (1–4, mild-unloading limb) were obtained with full informed consent (RCVS ethics approval, ref: 2017/14/Alves). OA scoring was performed on radiographs [VCOT, 2017, 30(6):377–384, 15–60, normal-severe OA], and α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-2 and kainate (KA)-1 GluR expression compared in diseased versus control tissues by immunohistochemistry (IHC). Results. We studied 25 dogs (various breeds, 4.88±3.02 years; 44% male; 56% female; 27.13±9.12kg). At the time of surgery, 44% dogs were on meloxicam alone, 40% on other therapeutic(s) and 16% on no therapeutics. Linear regression showed that OA score (mean 21.72±3.47) did not correlate with lameness score (mean 1.98±1.08), age or weight (p values of 0.7483, 0.4597, 0.1463; R. 2. values of 0.004563, 0.02400, 0.08951, respectively). Radiographic OA scores and lameness scores did not differ between therapeutic groups (one-way ANOVA, p=0.9229 and p=0.5541, respectively). GluRs (AMPA-2/KA-1) were expressed in CrCL and medial meniscus, with increased labelling in the CrCL epiligamentous region in diseased tissues, where microanatomy was disrupted. Conclusions. In this population, OA scores do not correlate with lameness scores, age, weight, and therapeutics at the time of surgery. Variable GluR expression in diseased tissues implicates glutamate signalling in this pathology. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Abstract. OBJECTIVES. Cam femoroacetabular impingement (FAI – femoral head-neck deformity) and developmental dysplasia of the hip (DDH – insufficient acetabular coverage) constitute a large portion of adverse hip loading and early degeneration. Spinopelvic anatomy may play a role in hip stability thus we examined which anatomical relationships can best predict range of motion (ROM). METHODS. Twenty-four cadaveric hips with cam FAI or DDH (12:12) were CT imaged and measured for multiple femoral (alpha angles, head-neck offset, neck angles, version), acetabular (centre-edge angle, inclination, version), and spinopelvic features (pelvic incidence). The hips were denuded to the capsule and mounted onto a robotic tester. The robot positioned each hip in multiple flexion angles (Extension, Neutral 0°, Flexion 30°, Flexion 60°, Flexion 90°); and performed internal-external rotations to 5 Nm in each position. Independent t-tests compared the anatomical parameters and ROM between FAI and DDH (CI = 95%). Multiple linear regressions determined which anatomical parameters could predict ROM. RESULTS. The FAI group demonstrated restricted ROM in deep hip flexion, with DDH showing higher ROM in Flexion 30° (+20%, p = 0.03), 60° (+31%, p = 0.001), and 90° (+36%, p = 0.001). In Neutral 0° and Flexion 30°, femoral neck and version angles together predicted ROM (R. 2. = 60%, 58% respectively); whereas in Flexion 60°, pelvic incidence and femoral neck angle predicted ROM (R. 2. = 77%). In Flexion 90°, pelvic incidence and radial alpha angle together predicted ROM (R. 2. = 81%), where pelvic incidence alone accounted for 63% of this variance. CONCLUSIONS. Pelvic incidence is essential to predict hip ROM. Although a cam deformity or acetabular undercoverage can elevate risks of labral tears and progressive joint degeneration, they may not be primary indicators of restrictive hip impingement or dysplastic instability. Better delineating additional spinopelvic characteristics can formulate early diagnostic tools and improve opportunities for nonsurgical management. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

No therapeutic strategy, administered in the early stage of osteoarthritis (OA), is fully able to block the degenerative and inflammatory progress of the pathology, whose only solution remains surgery. Aiming to identify minimally invasive therapies able to act on both degenerative and inflammatory processes, infiltrative treatments based on mesenchymal stem cells represent a promising solution due to their proliferative, immunomodulatory, anti-inflammatory, and paracrine ability. Accordingly, the aim of the present study was to investigate the performance of different cell therapies (stem cells from adipose tissue, ADSCs, stromal vascular fraction, SVF, and culture expanded, AECs vs negative control NaCl) in the treatment of OA. An in vivo model of early OA was developed in sheep knee (research protocol N.62/2018-PR date 29/01/2018 approved by the local Ethical Committee). Three and six months after the treatments injections, gross evaluation of articular surfaces (damage score, DS), histological (cartilage thickness, Th; fibrillation index, FI; collagen II content, C2) and mechanical assessment (elastic modulus, E; stress-relaxation time, τ) of cartilage were carried out. Due to the importance of the relationship between structure/composition (histology) and function (mechanics), this study investigated which of the revealed parameters were involved in such relation and how they were influenced by the level of degeneration and by the specific cell treatment, thus to better understand cell-tissue interaction. A statistically significant multi-variable linear regression model was found between τ and Th, FI, C2 (R2 0.7, p-value 8.39E-5). The relation was particularly strong between τ and C2 (p-value 7E-4), with a positive coefficient of 0.92. This is in agreement with literature, where a higher cartilage viscosity was related to a major content of collagen. By dividing the samples in two groups depending on cartilage damage, the more degenerated group (DS > 5) showed statistically significant lower C2 (p-value 0.0124) and τ (p-value 0.05), confirming that collagen content and viscosity decrease with OA grade increasing. Averaging the entire group of samples, the OA degeneration progressed between 3 and 6 months after, and despite, the treatment. But focusing on specific treatments, SVF and AECs differed from the general trend, inducing a higher amount of collagen at 6 months respect to 3 months. Moreover, articular cartilage treated by AECs and, overall, SVF showed a higher content of collagen and a major viscosity respect to the other treatments. We conclude that an injection of mesenchymal stem cells from stromal vascular fraction in early OA articulations could hinder the degenerative process, preserving or even restoring collagen content and viscosity of the articular cartilage

Background. Total knee replacement (TKR) is an effective operation for many patients, however approximately 20% of patients experience chronic pain and functional limitations in the months and years following their TKR. If modifiable pre-operative risk factors could be identified, this would allow patients to be targeted with individualised care to optimise these factors prior to surgery and potentially improve outcomes. Psychosocial factors have also been found to be important in predicting outcomes in the first 12 months after TKR, however their impact on long-term outcomes is unknown. This study aimed to identify pre-operative psychosocial predictors of patient-reported and clinician-assessed outcomes at one year and five years after primary TKR. Patients and methods. 266 patients listed for a Triathlon TKR because of osteoarthritis were recruited from pre-operative assessment clinics at one orthopaedic centre. Knee pain and function were assessed pre-operatively and at one and five years post-operative using the WOMAC Pain score, WOMAC Function score and American Knee Society Score (AKSS) Knee score. Pre-operative depression, anxiety, catastrophizing, pain self-efficacy and social support were assessed using patient-reported outcome measures. Statistical analyses were conducted using multiple linear regression and mixed effect linear regression, and adjusted for confounding variables. Results. Higher anxiety was a predictor of worse self-reported pain at one year post-operative. Higher anxiety and catastrophizing were predictive of worse self-reported function at one year post-operative. No psychosocial factors were associated with any outcome measures at five years post-operative. Analysis of change over time found that patients with higher pain self-efficacy had lower pre-operative pain and experienced less improvement in pain up to one year. Higher pain self-efficacy was associated with less improvement in the AKSS up to one year post-operative but more improvement between one and five years post-operative. Conclusion. This study found that pre-operative anxiety and catastrophizing influence outcomes at one year after TKR, highlighting that some patients may benefit from targeted psychological interventions to reduce these risk factors and improve outcomes. However, none of the psychosocial variables assessed were predictors of outcomes at five years post-operative, suggesting that the negative effects of anxiety and catastrophizing on outcome do not persist in the longer term

Achilles tendon (AT) rupture may lead to complaints of heel pain. In forefoot ulcer patients AT lengthening is used to transfer pressure from forefoot to the heel. The primary aim was to investigate if AT was longer or associated with changes in pedobaric measurements, in particular heel pressure, on the injured leg 4–5 years after the injury. Methods. We invited all participants from an RCT (n=56) of conservatively treated AT Rupture (ATR) with or without early weight-bearing (early-WB, non-WB). 37 patients participated, 19 from early-WB (1 re-rupture (RR)), and 18 from non-WB (2 RR). Time from injury to follow up was 4,5 years (4,1 to 5,1). AT length was measured using ultrasound with a validated protocol. Foot pressure mapping (FPM) was measured barefoot, using an EMED platform (novel, Germany), with 5 trials for each foot. Statistics. T-test for limb to limb comparisons and linear regression for correlations was applied. Results. We found no differences in any of the variables between the early-WB and non-WB groups. Compared to the uninjured limb, the Achilles tendon was an average of 1.8 (1.2–2.3) cm longer on the injured limb (p<0.001). When comparing the ratio of the medial (1–2 ray) to lateral (3–5 ray) forefoot mean peak pressure, we found no difference between the injured and healthy limb (p=0.26). Mean heel peak pressure was not different from the injured to the healthy leg (difference was 3,9 (−1,7 – 9,45) p=0,17). Heel lift-off was delayed in the injured limb by 2% (0.4%–4.4%) of the total roll over process (ROP) (p= 0.02). Achilles tendon length could not be linked to either heels lift-off or mean peak pressure of the heel using linear regression (p 0.27 to 0.78). Conclusion. Conservatively treated Achilles tendon ruptures were approximately 1.8 cm longer. A subtle change in the time of heel rise could be detected on the injured limb, but contrary to our expectations AT length did not correlate to time of heel lift or mean heel peak pressure. This is in contrast to the common practice in diabetics, where the Achilles tendon is elongated to relieve pressure from the forefoot – a mechanism we cannot observe from elongation of the tendon after acute rupture, treated conservatively - though this study is underpowered

Growth factors are reported to play an important role in healing after acute Achilles tendon rupture (ATR). However, the association between growth factors and patient outcome has not been investigated previously. The aim of this retrospective study is to identify growth factors and related proteins which can be used as predictors of healing after ATR, ethical approval was obtained from the Regional Ethical Review Committees in Sweden and followed the guidelines of the Declaration of Helsinki. The study included 28 surgically treated patients (mean age 39.11 ± 8.38 yrs) with acute ATR. Healing was assessed by microdialysate two weeks after the surgery and performed on both injured and contralateral un-injured leg. The microdialysates were analyzed by proteomics based on mass spectrometry (MS) to detect growth factor expressions in ATR patients. One year after the surgery, healing outcomes were evaluated by patient-reported Achilles tendon Total Rupture Score (ATRS), Foot and Ankle Outcome Score (FAOS), and functional outcomes by heel-rise test. A total of 1549 proteins were detected in the microdialysates of which 20 growth factor/ related proteins were identified. 7 of these were significantly up-regulated (IGFBP2, Fold change (FC) = 4.07, P = 0.0036; IGFBP4, FC = 3.06, P = 0.009; CTGF, FC = 15.83, P = 0.003; HDGF, FC = 4.58, P = 0.003; GRB2, FC = 14.8, P = 0.0004; LTBP1, FC = 12.08, P = 0.0008; TGFBI, FC = 5.54, P = 0.001) and 1 down-regulated (IGFBP6) in the injured compared to the contralateral healthy side. Linear regression analysis revealed that TGFB1 was positively associated with improved ATRS (r = 0.585, P = 0.04) as well to ATRS subscales: less limitation in running (r = 0.72, P = 0.004), less jumping limitation (r = 0.764, P = 0.001) and less limitation caused by decreased tendon strength (r = 0.665, P = 0.012). Interestingly, all 7 up-regulated proteins were positively associated with less jumping limitations (IGFBP2, r = 0.667, P = 0.015; IGFBP4, r = 0.675, P = 0.013; CTGF, r = 0.668, P = 0.015; HDGF, r = 0.672, P = 0.014; GRB2, r = 0.665, P = 0.016; LTBP1, r = 0.663, P = 0,016). No associations were observed among any of the growth factor and FAOS or patient's functional outcomes. We conclude that growth factors and related proteins play a crucial role in ATR healing. More specifically, TGFB1 may be used as prognostic biomarker of the patient-reported outcome 1-year post-surgery. These results may be used to develop more specific treatments to improve ATR healing

Background. Although there are predictive equations that estimate the total fat mass obtained from multiple-site ultrasound (US) measurements, the predictive equation of total fat mass has not been investigated solely from abdominal subcutaneous fat thickness. Therefore, the aims of this study were; (1) to develop regression-based prediction equations based on abdominal subcutaneous fat thickness for predicting fat mass in young- and middle-aged adults, and (2) to investigate the validity of these equations to be developed. Methods. The study was approved by the Local Research Ethics Committee (Decision number: GO 19/788). Twenty-seven males (30.3 ± 8.7 years) and eighteen females (32.4 ± 9.5 years) were randomly divided into two groups as the model prediction group (19 males and 12 females) and the validation group (8 males and 6 females). Total body fat mass was determined by dual-energy X-ray absorptiometry (DXA). Abdominal subcutaneous fat thickness was measured by US. The predictive equations for total fat mass from US were determined as fat thickness (in mm) × standing height (in m). Statistical analyses were performed using R version 4.0.0. The association between the total fat mass and the abdominal subcutaneous fat thickness was interpreted using the Pearson test. The linear regression analysis was used to predict equations for total body fat mass from the abdominal subcutaneous fat thickness acquired by US. Then these predictive equations were applied to the validation group. The paired t-test was used to examine the difference between the measured and the predicted fat masses, and Lin's concordance correlation coefficient (CCC) was used as a further measure of agreement. Results. There was a significant positive moderate correlation between the total fat mass and the abdominal subcutaneous fat thickness × height in the model prediction group of males (r = 0.588, p = 0.008), whereas significant positive very strong correlation was observed in the model prediction group of females (r = 0.896, p < 0.001). Predictive equations for DXA-measured total body fat mass from abdominal subcutaneous fat thickness using US were as follows: for males “Fat mass-DXA = 0.276 × (Fat thickness-US × Height) + 17.221” (R. 2. = 0.35, SEE = 3.6, p = 0.008); for females “Fat mass-DXA = 0.694 x (Fat thickness-US × Height) + 7.085” (R. 2. = 0.80, SEE = 2.8, p < 0.001). When fat mass prediction equations were applied to the validation groups, measured- and estimated-total fat masses in males and females were found similar (p = 0.9, p = 0.5, respectively). A good level of agreement between measurements in males and females was attained (CCC = 0.84, CCC = 0.76, respectively). Conclusion. We developed and validated prediction equations that are convenient for determining total fat masses in young- and middle-aged adults using abdominal subcutaneous fat thickness obtained from the US. The abdominal subcutaneous fat thickness obtained from a single region by US might provide a noninvasive quick and easy evaluation not only in clinical settings but also on the field