The identification of the extent of neural damage in patients with acute or chronic spinal cord injury is imperative for the accurate prediction of neurological recovery. The changes in signal intensity shown on routine MRI sequences are of limited value for predicting functional outcome. Diffusion tensor imaging (DTI) is a novel radiological imaging technique which has the potential to identify intact nerve fibre tracts, and has been used to image the brain for a variety of conditions. DTI imaging of the spinal cord is currently only a research tool, but preliminary studies have shown that it holds considerable promise in predicting the severity of spinal cord injury. . This paper briefly reviews our current knowledge of this technique

Aims. The aim of this study was to use diffusion tensor imaging (DTI) to investigate changes in diffusion metrics in patients with cervical spondylotic myelopathy (CSM) up to five years after decompressive surgery. We correlated these changes with clinical outcomes as scored by the Modified Japanese Orthopedic Association (mJOA) method, Neck Disability Index (NDI), and Visual Analogue Scale (VAS). Methods. We used multi-shot, high-resolution, diffusion tensor imaging (ms-DTI) in patients with cervical spondylotic myelopathy (CSM) to investigate the change in diffusion metrics and clinical outcomes up to five years after anterior cervical interbody discectomy and fusion (ACDF). High signal intensity was identified on T2-weighted imaging, along with DTI metrics such as fractional anisotropy (FA). MJOA, NDI, and VAS scores were also collected and compared at each follow-up point. Spearman correlations identified correspondence between FA and clinical outcome scores. Results. Significant differences in mJOA scores and FA values were found between preoperative and postoperative timepoints up to two years after surgery. FA at the level of maximum cord compression (MCL) preoperatively was significantly correlated with the preoperative mJOA score. FA postoperatively was also significantly correlated with the postoperative mJOA score. There was no statistical relationship between NDI and mJOA or VAS. Conclusion. ms-DTI can detect microstructural changes in affected cord segments and reflect functional improvement. Both FA values and mJOA scores showed maximum recovery two years after surgery. The DTI metrics are significantly associated with pre- and postoperative mJOA scores. DTI metrics are a more sensitive, timely, and quantifiable surrogate for evaluating patients with CSM and a potential quantifiable biomarker for spinal cord dysfunction. Cite this article: Bone Joint J 2020;102-B(9):1210–1218

Aims. The aim of this study was to evaluate the time course of changes in parameters of diffusion tensor imaging (DTI) such as fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in patients with symptomatic lumbar disc herniation. We also investigated the correlation between the severity of neurological symptoms and these parameters. . Patients and Methods. A total of 13 patients with unilateral radiculopathy due to herniation of a lumbar disc were investigated with DTI on a 1.5T MR scanner and underwent micro discectomy. There were nine men and four women, with a median age of 55.5 years (19 to 79). The changes in the mean FA and ADC values and the correlation between these changes and the severity of the neurological symptoms were investigated before and at six months after surgery. . Results. The mean FA values were significantly lower (p = 0.0005) and mean ADC values were significantly higher (p = 0.0115) in compressed nerves than in intact nerves. Although the FA values increased significantly at six months after surgical treatment (p = 0.020), the ADC values decreased but not significantly (p = 0.498). There were strong correlations between the DTI parameters such as the FA value and the severity of the neurological symptoms as assessed using the Japanese Orthopaedic Association (JOA) score and the Roland-Morris Disability Questionnaire (RDQ). . Conclusion. This preliminary study suggests that it may be possible to use DTI to diagnose, quantitatively evaluate and follow-up patients with lumbar nerve entrapment. Take home message: DTI is a potential tool for functional diagnosis of lumbar nerve damage. Cite this article: Bone Joint J 2016;98-B:387–94

Reconstruction of the anterior cruciate ligament (ACL) allows to restore stability of the knee, in order to facilitate the return to activity (RTA). Although it is understood that the tendon autograft undergoes a ligamentous transformation postoperatively, knowledge about longitudinal microstructural differences in tissue integrity between types of tendon autografts (ie, hamstring vs. patella) remains limited. Diffusion tensor imaging (DTI) has emerged as an objective biomarker to characterize the ligamentization process of the tendon autograft following surgical reconstruction. One major limitation to its use is the need for a pre-injury baseline MRI to compare recovery of the graft, and inform RTA. Here, we explore the relationship for DTI biomarkers (fractional anisotropy, FA) between knees bilaterally, in healthy participants, with the hypothesis that agreement within a patient's knees may support the use of the contralateral knee as a reference to monitor recovery of the tendon autograft, and inform RTA. Fifteen participants with no previous history of knee injuries were enrolled in this study (age, 26.7 +/− 4.4 years; M/F, 7/8). All images were acquired on a 3T Prisma Siemens scanner using a secured flexible 18-channel coil wrapped around the knee. Both knees were scanned. A 3D anatomical Double Echo Steady State (DESS) sequence was acquired on which regions of interest (ROI) were placed consistent with the footprints of the ACL (femur, posteromedial corner on medial aspect of lateral condyle; tibia, anteromedial to intercondylar eminence). Diffusion images were acquired using fat saturation based on optimized parameters in-house. All diffusion images were pre-processed using the FMRIB FSL toolbox. The footprint ROIs of the ACL were then used to reconstruct the ligament in each patient with fiber-based probabilistic tractography (FBPT), providing a semi-automated approach for segmentation. Average FA was computed for each subject, in both knees, and then correlated against one another using a Pearson correlation to assess the degree of similarity between the ACLs. A total of 30 datasets were collected for this study (1/knee/participant; N=15). The group averaged FA (+/− standard deviation) for the FBPT segmented ACLs were found to equal 0.1683 +/− 0.0235 (dominant leg) and 0.1666 +/− 0.0225 (non-dominant leg). When comparing both knees within subjects, reliable agreement was found for the FBPT-derived ACL with a linear correlation coefficient (rho) equal to 0.87 (P < 0 .001). We sought to assess the degree of concordance in FA between the knees of healthy participants with hopes to provide a method for using the contralateral “healthy” knee in the comparison of autograft-dependent longitudinal changes in microstructural integrity, following ACL reconstruction. Our results suggest that good agreement in anisotropy can be achieved between the non-dominant and dominant knees using DTI and the FBPT segmentation method. Contralateral anisotropy of the ACL, assuming no previous injuries, may be used as a quantitative reference biomarker for monitoring the recovery of the tendon autograft following surgical reconstruction, and gather further insight as to potential differences between chosen autografts. Clinically, this may also serve as an index to supplement decision-making with respect to RTA, and reduce rates of re-injuries

Study Design: An in-vivo serial magnetic resonance imaging study of diffusion characteristics in human lumbar discs over 24 hours in healthy volunteers and patients with low back pain. Objective: Nutrition to the disc is solely by diffusion but no firm data is available on diffusion pattern in humans. This study reports diffusion patterns in a human population studied and documents the 24-hour diffusion pattern. Methods: T1-weighted images were obtained pre and post-contrast with Gadodiamide-0.3mmol/kg at 5, 10 minutes, 2, 4, 6, 12 and 24hours. Diffusion was calculated by measuring signal intensity values in seven regions of interest (anterior and posterior annulus, anterior, posterior, peripheral (PNP) and central (CNP) parts of nucleus pulposus (NP). Enhancement percentage (EP), Peak enhancement percentage (PEP) and time to achieve PEP (T. max. ) were calculated. Subjects: Of the 215 discs in 43 persons (10 volunteers and 33 patients) 96 discs were normal and considered for study. Results: Diffusion occurred mainly from the endplate (rather than annulus). The mean EP of PNP and CNP at 5 minutes was 6.7, 3.9; 10minutes was 7.5, 4.0; 2 hours was 36.6, 17.9; 4hrs was 42.8, 29.8; 6hrs was 51.7, 40.5; 12hrs was 35.9, 27.8 and 24 hours was 33.3, 27.9. Though PEP was achieved at 6 hours in NP, the CNP lagged behind throughout. Univariate ANOVA showed that there was significant difference (p< 0.0001) in PEP of NP between the age groups of less than ten (72.4) and higher (37.9). The mean PEP at the NP of lower two discs (26.8) was less compared to upper two discs 41.0(p=0.059). Stepwise linear regression analysis showed that diffusion to the CNP was significantly influenced by age (R. 2. =0.324), followed by level of disc (R. 2. =0.5). Conclusion: This is the first study to document the normal 24-hour diffusion pattern across lumbar discs. The data can form the basis for comparison of diffusion changes in degeneration, Modic’s endplate changes and smoking

The aim of this study was to measure diffusion coefficients of solutes through the disc in relation to molecular weight. The intervertebral disc is avascular thus nutrients and other factors from the blood supply are transported into the intervertebral disc by diffusive and convective flow. For small solutes such as lactate and glucose and oxygen, diffusion appears to predominate however convection may aid transport of larger molecules such as growth factors. At present there however, there is virtually no information on diffusion of solutes of different molecular weights through the disc; this information is necessary for assessing and modelling transport pathways. Diffusion coefficients were measured in nucleus and annulus sections of bovine intervertebral discs by a novel method which prevented tissue swelling and proteoglycan loss. Briefly strips of fluorescent or radiolabelled solute-saturated filter-paper were placed adjacent to the disc and the resulting concentration gradients measured at appropriate times. Solute sizes from 0.01 to 70 kDa were investigated. All results are reported as mean + s.e.m (n=6). Diffusion coefficients (D) fell steeply with increase in molecular weight following a log-log relationship as predicted by theory. For small solutes (lactate) D for the outer annulus was 3.4 ± 1.1.10. −6. cm. 2. /sec while for 70 kDa dextran, D was 1.4 ± 0.6.10. −7. There was no significant difference between values of D for nucleus and outer annulus for any solute. Diffusion coefficients through the disc follow relationships seen in other cartilages and are dependant on tissue properties and molecular weight. The similarities between values for nucleus and outer annulus demonstrate the conflicting roles of proteoglycan and water contents in governing diffusion through the matrix with D decreasing both with increase in proteoglycan and decrease in water content

The management of post-traumatic bone infections relies on antibiotic therapy and surgical debridement. Antibiotic concentration in infected bone is a major determinant of response to medical treatment. The aim is to assess glycopeptides, fluoroquinolones and carbapenems diffusion in infected human bone, since they are widely used for treating bone infections. Twenty-four patients with septic pseudoarthrosis undergoing surgical debridement and treated with glycopeptides/fluoroquinolones/carbapenems iv for > 1 week were studied. Plasma and bone specimens were collected intraoperatively at a mean of 4.8h after antibiotic administration. Antibiotic concentrations were measured by the HPLC-UV method. Five patients received vancomycin: mean bone concentrations were 2.4mg/L in cortical and 7.1mg/L in cancellous bone, with a bone/plasma extraction of 12% and 36%, respectively. Nine patients were treated with teicoplanin: bone concentrations were 2.5mg/L for cortical and 8.3mg/L for cancellous bone (14% and 46% of plasma levels). Five patients received a fluoroquinolone. Ciprofloxacin concentrations were 1.8mg/L in cortical bone and 30.2mg/L in cancellous and newly formed bone (respective bone/plasma ratios 1.06 and 8.4). Levofloxacin concentrations were 0.3 and 2.69mg/L in cortical and cancellous bone, with diffusion rates of 12% and 108%, respectively. Five patients received a carbapenem. Imipenem diffusion rates were respectively 7.5% and 58.3% for cortical and cancellous bone (bone concentrations 0.09 mg/L and 0.7 mg/L). Meropenem levels were 1.2 mg/L and 5.2 mg/L in cortical and cancellous bone, with respective diffusion rates of 3.6% and 15%. Both glycopeptides provided concentrations exceeding the MIC of infecting agents, with satisfactory bone diffusion. Fluoroquinolones, especially ciprofloxacin, displayed excellent diffusion. Ciprofloxacin concentrations in cancellous and new bone were far higher than in plasma, suggesting accumulation into highly vascularized tissue. Imipenem had better diffusion than meropenem, but bone levels were under the MIC of susceptible agents. Glicopeptides and fluoroquinolones appear excellent options for bone infections, while carbapenems should be a second choice treatment

Introduction. A new triggered electromyography test for detection of stimulus diffusion to intercostal muscles of the contralateral side during thoracic pedicle screw placement was evaluated. Experimental research was carried out in order to determine if, using this test, neural contact at different aspects of the spinal cord and nerve roots could be discriminated. Methods. Nine industrial pigs (60–75 kg) had 108 pedicle screws placed bilaterally in the thoracic spine (T8–T13). Neural structures were stimulated under direct vision at different anatomic locations from T9 to T12. Recording electrodes were placed over the right and left intercostal muscles. Increasing intensity of the stimulus was applied until muscle response was detected at the contralateral side (diffusion phenomenon). After this first experiment, the thoracic spine was instrumented. Screws were placed in the pedicle in two different positions, the anatomic intrapedicular location and with purposeful contact with the neural elements. Results. Response thresholds to direct stimulation of nerve root at different points were significantly lower than those obtained by stimulation of the dorsal aspect of the spinal cord (0.44±0.22 mA vs 1.38±0.71 mA). However, a 24-fold stimulation intensity (6.50±0.29 mA) was necessary to obtain diffusion of the EMG response to the opposite left side if the right nerve root was stimulated. Only a 2-fold increment (3.17±0.93 mA) was able to elicit diffusion of EMG responses to the contralateral side when stimulation was applied to the dorsal aspect of the spinal cord. Contralateral EMG responses after high increases of stimulation thresholds indicated nerve root contact. Diffusion phenomenon after low threshold increments reflected medullar contact. Electromyography recordings after triggered stimulation of the screws showed that only screws in contact with the spinal cord had significantly lower responses (2.72±1.48 mA). Conclusion. Stimulus-triggered EMG could only discriminate screws with violation of the medial pedicle wall if they were contact with neural tissues. Recording EMG-potentials at the contralateral paraspinal muscles (stimulus diffusion phenomenon) proved to be a reliable method to discriminate which of the neural structures was at risk

INTRODUCTION. One of the recent advances in the hard-on-hard hip arthroplasty is the development of a new material of diffusion hardened oxidised zirconium (DHOxZr). The DHOxZr material consists of a ceramic layer on the top surface which is supported by a thick oxygen diffusion hardened (DH) zone underneath. With the desired properties of metal substrate, ceramic surface and a gradient structure of the oxygen diffusion zone, the DHOxZr-on-DHOxZr bearing combination is expected to produce low wear and minimal metal ions. This can possibly address the concerns associated with metal hypersensitivity associated with metal on metal bearings and fracture risk associated with ceramics. The aim of this study was to evaluate the wear of DHOxZr-on-DHOxZr as a possible hard on hard bearing combination in hips. METHODS. Three pairs of 50 mm DHOxZr prototype hip joint devices, each consisting of a DHOxZr modular head and a DHOxZr liner were wear tested in a ProSim hip joint simulator under standard testing conditions used by the Implant Development Centre (IDC), Smith & Nephew, Leamington Spa for 5 million cycles (Mc). The flexion/extension was 30° and 15°. The internal/external rotation was ± 10°. The force was Paul-type stance phase loading, with a maximum load of 3 kN and a standard ISO swing phase load of 0.3 kN. The test frequency was 1 Hz. Gravimetric analysis was carried out at 0, 0.5, 1, 2, 3, 4 & 5 million cycles. The lubricant was new born calf serum with 2 g/l sodium azide concentration diluted with de-ionised water to achieve average protein concentration of 20 g/l. Lubricant was changed every 0.25Mc during the first million cycles of the test and at every 0.33 Mc from 1 to 5Mc. RESULTS. A biphasic wear pattern was observed for the DHOxZr on DHOxZr devices during the test, with a running in phase from 0–1 Mc and a steady state phase from 1–5 Mc. At a confidence level of 95%, the mean wear rate was 0.21 ±0.06 mm3/Mc during the running-in stage, and the wear rate was reduced to 0.01 ±0.03 mm3/Mc during the steady state for the device tested. The wear volume loss of the DHOxZr on DHOxZr devices was significantly lower than that generated by CoCrMo metal on metal (MoM) devices (p < 0.05) under identical simulator test conditions

The diffusion of Fucidin, gentamicin, and clindamycin from acrylic cement was tested in an in vitro system. The activity of Fucidin was very short-lived and only against gram-positive organisms; gentamicin inhibited gram-positive and gram-negative organisms for twenty-two and eleven days respectively; clindamycin had significant action only against gram-positive organisms and retained some activity for fifty-six days. We suggest that the destruction of organisms in the tissues is more likely to be achieved by topical and intravenous administration of antibiotics during the operation than by incorporation of antibiotic in the cement

We investigated the possible use of acrylic cement containing chemotherapeutic drugs in the treatment of malignant lesions in bone. The diffusion of methotrexate (MTX) from methylpolymethacrylate implants was studied in vitro: polymerisation of the cement did not destroy the drug; liberation began immediately and about 10% was released by 18 hours. Some release continued for as long as six months. In vivo experiments on rats with induced osteosarcoma showed that MTX in cement had both local and general effects which were dependent on the dosage. A series of 17 large dogs with spontaneous osteosarcoma were then treated by local resection and cement containing MTX. General chemotherapeutic effects were detectable from 2 hours to 5 days, survival was increased and local recurrence was reduced, but there were four cases of delayed wound healing. Preliminary studies in human patients confirm the possibility that this method of local chemotherapy could be a useful addition to the treatment of malignant tumours of bone

Antibiotic concentration in infected bone is a major determinant of clinical response. As glycopeptides and fluoroquinolones are widely used for the treatment of bone infections, aim of our study was to assess their diffusion in infected human bone. Patients with a posttraumatic septic pseudoarthrosis undergoing debridement of infected tissue, who received a glycopeptide or a fluoroquinolone for > 1 week, were studied. Plasma and bone specimens were collected intraoperatively for phamacokinetic and microbiologic assays at a mean of 4.1h after antibiotic administration. Bone samples were crushed and concentrations were measured by HPLC-UV method. Overall plasma exposure was also determined with daily sampling. 16 patients were studied. 6 patients received iv vancomycin 1 g bid over a 1-hr infusion Bone cultures grew E. faecalis, MRSA and MRSE (MIC < 2 mg/L). Mean plasma concentration of vancomycin at time of osteotomy was 19.8 mg/L. Mean bone concentrations were 2.4 mg/L in cortical and 7.1 mg/L in cancellous bone, with a mean bone extraction of 12 % and 36 %, respectively. 4 patients were treated with iv teicoplanin 10/mg/Kg for MRSA infection (MIC < 2 mg/L). Mean bone concentrations were 8.9 mg/L and 37 mg/l respectively for cortical and cancellous bone, respectively corresponding to 6% and 25% of plasma levels. Six patients were treated with a fluoroquinolone. 3 patients received iv ciprofloxacin 400mg bid and E. coli grew from bone samples(MIC = 0.5 mg/L). Mean Plasma concentration of ciprofloxacin at the time of osteotomy was 3.6 mcg/mL. Mean bone concentrations were 1.7 mg/L in cortical bone and 30.2 mg/L in cancellous and newly formed bone, with respective bone/ plasma ratios of 0.5 and 8.4. 3 patients were administered iv levofloxacin 500mg qd and Enterobacter spp. were isolated (MIC = 1 mg/L). Mean plasma concentration at the time of surgery was 2.5 mcg/mL. Mean bone concentrations were 0.3 and 2.69 mcg/mL in cortical and cancellous bone, respectively. To our knowledge this is the first study that compares different antibiotic’s concentration in infected bone with the same dosing procedure. Both vancomycin and teicoplanin provided mean bone concentrations exceeding the susceptibility breakpoint of the infecting agents. Higher and constant glycopeptides plasma levels may be required for preventing recurrencies in bone infections. Only ciprofloxacin provided cortical bone concentrations higher than the susceptibility breakpoint of the infecting agent, and similar to those reported in non-infected bone. Ciprofloxacin concentration in cancellous bone and in bony callus were far higher than those detected in plasma, which may be related to an augmented vascularization and/or selective accumulation of fluoroquinolones into regenerating bone, as observed in children’s cartilage growth plate. Ciprofloxacin may be therefore preferred to levofloxacin

Introduction. The Z or “scarf” osteotomy was first described by Meyer in 1926 and then by Burutaran in 1976. It was later popularised by Weil in the USA and Barouk in Europe in the 1990's and is now an accepted technique that forms part of a surgeons' armamentarium. The theory of Diffusion of Innovations was described by Rogers in 1962 to explain how novel ideas are accepted into practice across different industries, including medicine. It has never previously been used to study the adoption of ideas in foot and ankle surgery. Methods. This paper uses publication volume as a surrogate marker for adoption, as described previously by the authors. Briefly, a systematic review of the literature was carried out. MESH headings included ‘Hallux Valgus’, and ‘osteotomy’ or ‘SCARF’ or ‘Z osteotomy’ or ‘bunionectomy’. 2818 publications were identified and the abstracts were reviewed excluding 2699 publications for non-relevance. The data was analysed by year of publication, country of origin, as well as for level of evidence. Results. There were 120 publications relating to SCARF osteotomy, which when plotted on a graph produced an s shaped curve. 58% of publications came from Europe and 38% from the USA. There was only a single level 1 paper published in 2008. Discussion. This study confirms that publication volume is a surrogate marker for adoption and that SCARF osteotomy became adopted by the late 2000's as indicated by the plateau on an s-shaped curve. Post market surveillance has led to a further rise in recent publications indicating that certain issues still need resolving before the laggards adopt this technique. Despite SCARF having been around for more than 80 years, very little high level evidence has been published of its effectiveness. Recommendations are made as to how future innovations should be introduced in foot and ankle surgery

Intervertebral discs (IVD) provide flexibility to the back and ensure functional distributions of the spinal loads. They are avascular, and internal diffusion-dependent metabolic transport is vital to supply nutrients to disc cells1, but interactions with personalized IVD shapes and mechanics remain poorly explored. Poromechanical finite element models of seven personalized lumbar IVD geometries, with mean heights ranging from 8 to 16 mm were coupled with a reactive oxygen, glucose and lactate transport model linked with tissue deformations and osmosis . In previous studies, reduced formulations of the divergence of the solute flux (∇ .J = ∇ . (D∇ C) = ∇ D. ∇ C +D∇ 2C) ignored the dependence of the diffusion on the deformation gradients, ∇ D. ∇C. We simulated this phenomenon to explore its significance in mechano-metabolic -transport couplings, in the different geometries, over 24h of simulated rest (8h) and physical activity (16h). ∇ D. ∇ C affected the daily variations of glucose concentrations in IVD thinner than 12 mm but with neglectable variation ranges, while not considering ∇ D. ∇ C in taller discs only slightly overestimated the glucose concentration. Most importantly, tall IVD had nearly 60% less glucose than thin IVD, with local drops below the concentration of 0.5 mM, considered to be critical for disc cells3, in the anterior nucleus pulposus. On the one hand, previous reduced formulations for mechanometabolic-transport models of the IVD seem acceptable, even for patient-specific modelling. On the other hand, tall IVD might suffer from unfortunate combinations of deformation-dependent solute diffusion and large diffusion distances, which may favor early. Acknowledgements: Catalan Government and European Commission (2020 BP 00282; ERC-2021-CoG-O-Health-101044828)

Aims. There is a lack of biomaterial-based carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotics for bone infections. RIF is also known for causing rapid development of antibiotic resistance when given as monotherapy. This in vitro study evaluated a clinically used biphasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN). Methods. The CaS/HA composites containing RIF/GEN/VAN, either alone or in combination, were first prepared and their injectability, setting time, and antibiotic elution profiles were assessed. Using a continuous disk diffusion assay, the antibacterial behaviour of the material was tested on both planktonic and biofilm-embedded forms of standard and clinical strains of Staphylococcus aureus for 28 days. Development of bacterial resistance to RIF was determined by exposing the biofilm-embedded bacteria continuously to released fractions of antibiotics from CaS/HA-antibiotic composites. Results. Following the addition of RIF to CaS/HA-VAN/GEN, adequate injectability and setting of the CaS/HA composites were noted. Sustained release of RIF above the minimum inhibitory concentrations of S. aureus was observed until study endpoint (day 35). Only combinations of CaS/HA-VAN/GEN + RIF exhibited antibacterial and antibiofilm effects yielding no viable bacteria at study endpoint. The S. aureus strains developed resistance to RIF when biofilms were subjected to CaS/HA-RIF alone but not with CaS/HA-VAN/GEN + RIF. Conclusion. Our in vitro results indicate that biphasic CaS/HA loaded with VAN or GEN could be used as a carrier for RIF for local delivery in clinically demanding bone infections. Cite this article: Bone Joint Res 2022;11(11):787–802

The avascular nature of articular cartilage relies on diffusion pathways to obtain essential nutrients and molecules for cellular activity. Understanding these transport pathways is essential to maintaining and improving the health of articular cartilage and ultimately synovial joints. Several studies have shown that joint articulation is associated with fluid and solute uptake although it remains unclear what role sliding motion independently plays. This study investigates the role of sliding with a non-stationary contact area on the uptake of small molecular weight tracers into articular cartilage. Ten-millimeter diameter cartilage-bone plugs were obtained from porcine knee joints and sealed into purpose made diffusion chambers. The chambers were designed to eliminate diffusion from the radial edge and only allow diffusion through the articular surface. The bone side of the chamber was filled with PBS to maintain tissue hydration while the cartilage side was filled with 0.01mg/ml fluorescein sodium salt (FNa) prepared using PBS. Sliding loads with a non-stationary contact area were applied across the articular surface by a custom apparatus using a 4.5 mm diameter spherical indenter. A moving contact area was chosen to represent physiological joint motions. Reciprocal sliding was maintained at a rate of 5 mm/s for 2 and 4 hours. Control samples were subject to passive diffusion for 0, 4, and 88 hours. After diffusion tests, samples were snap frozen and 20 µm cross-sectional cuts were taken perpendicular to the sliding direction. Samples were imaged using a Zeiss AxioImager M2 epifluorescent microscope under 5× magnification with a filter for FNa. Intensity profiles were mapped from the articular surface to the subchondral bone. Unloaded control samples demonstrated minimal solute uptake at 4 hours penetrating less than 5% of the total cartilage depth. By 88 hours solute penetration had reached the subchondral bone although there was minimal accumulation within the cartilage matrix indicated by the relatively low intensity profile values. Samples that had been subjected to reciprocal sliding demonstrated accelerated penetration and solute accumulation compared to unloaded samples. After 1 hour of reciprocal sliding, the solute had reached 40% of the cartilage depth, this increased to approximately 80% at 4 hours, with much higher intensities compared to unloaded controls. Sliding motion plays an important role in the uptake of solutes into the cartilage matrix. Maintaining joint motion both post injury and in the arthritic process is a critical component of cartilage nutrition. Samples that had been subject to reciprocal sliding demonstrated accelerated solute penetration and accumulation in the cartilage matrix, exceeding steady state concentrations achieved by passive diffusion

Osteoarthritis (OA) leads to articular cartilage degradation, following complex dysregulation of chondrocyte's metabolism towards a catabolic state. Mechanical and biochemical signals are involved and need to be considered to understand the condition. Regulatory network-based models (RNM) successfully simulated the biological activity of the chondrocyte and the transduction of mechanical signals at the molecular and cell levels. However, the knowledge gap between single-cell regulation and intercellular communication in tissue volumes hinders the interpretability of such models at larger scales. Accordingly, a novel tissue-level biochemical model is proposed. We hypothesise that it is possible to simulate interacting network effects through the transport of diluted species in a finite-element model, to grasp relevant dynamics of cell and tissue regulation in OA. Chondrocyte RNM equations were translated into a reaction term of 18 multi-species diffusion model (e.g., 3 anti-inflammatory and 8 pro-inflammatory interleukins, 3 pro-anabolic and 1 pro-catabolic growth factors, 2 nociceptive factors and 2 pro-inflammatory cytokines). Elements with RNM reaction terms represented the chondrocytes and were distributed randomly through the model, according to known cellular density in the knee cartilage, and could both react to and produce diffusive entities through the pericellular matrix, associated with reduced diffusion coefficients. The model was constructed over a 2D square of 0.47 mm sides considered to be in the middle of the cartilage, so boundary conditions were settled as periodic. Different simulations were initialised with initial concentrations of either healthy or pro-OA mediators. Preliminary results showed that, independently of the initial conditions, the chondrocytes successfully evolved into anabolic states, in absence of sustained pro-catabolic external stimulations, in contrast to single-cell RNM [2]. Our intercellular model suggests that paracrine communication may increase robustness towards cartilage maintenance, and future tests shall reveal new OA dynamics. Acknowledgements: Funding was provided by the European Commission (ERC-2021-CoG-O-Health-101044828)

Objectives. Inflammation of the retrocalcaneal bursa (RB) is a common clinical problem, particularly in professional athletes. RB inflammation is often treated with corticosteroid injections however a number of reports suggest an increased risk of Achilles tendon (AT) rupture. The aim of this cadaveric study was to describe the anatomical connections of the RB and to investigate whether it is possible for fluid to move from the RB into AT tissue. Methods. A total of 20 fresh-frozen AT specimens were used. In ten specimens, ink was injected into the RB. The remaining ten specimens were split into two groups to be injected with radiological contrast medium into the RB either with or without ultrasonography guidance (USG). Results. In specimens injected with ink, diffusion outside the RB was observed with staining of the anterior portion of the AT. In eight contrast-injected specimens (five USG, three non-USG), a similar localised diffusion pattern was observed, with the contrast identified superiorly and anteriorly. In two contrast-injected specimens (non-USG), the diffusion pattern was more extensive. Conclusion. This study confirmed the existence of connections between the RB and the AT, especially rich in the anteroinferior portion of the tendon, which should be considered a weak zone for substances injected into the RB. We hypothesise that this part of the AT might be most vulnerable to rupture after corticosteroid injections. Cite this article: P. A. Pękala, B. M. Henry, J. R. Pękala, K. Piska, K. A. Tomaszewski. The Achilles tendon and the retrocalcaneal bursa: An anatomical and radiological study. Bone Joint Res 2017;6:446–451. DOI:10.1302/2046-3758.67.BJR-2016-0340.R1

Objectives. Vancomycin and fosfomycin are antibiotics commonly used to treat methicillin-resistant Staphylococcus aureus (MRSA) infection. This study compares the in vitro inhibitory effects against MRSA of articulating cement spacers impregnated with either vancomycin or fosfomycin. Methods. Vancomycin-impregnated articulating cement spacers and fosfomycin-impregnated articulating cement spacers were immersed in sterile phosphate-buffered saline (PBS) solutions and then incubated. Samples were collected for bioactivity evaluation. The aliquots were tested for MRSA inhibition with the disc diffusion method, and the inhibition zone diameters were measured. The inhibition zone differences were evaluated using the Wilcoxon Rank Sum Test. Results. The vancomycin group had significantly larger inhibition zones than the fosfomycin group from day three through to completion of the fourth week of incubation (p < 0.001). The vancomycin group exhibited a MRSA inhibition zone up to four weeks but the fosfomycin group showed an inhibition zone for only three days and after that did not show the the potential to inhibit MRSA. Conclusion. This in vitro study found that the inhibitory effect of vancomycin-impregnated articulating cement spacers against MRSA outperformed fosfomycin-impregnated articulating cement spacers. Further comparing our results to other published reports suggests there might be a limitation of the disc diffusion bioassay to show a large inhibitory zone in a high concentration of a highly soluble antibiotic. Cite this article: V. Yuenyongviwat, N. Ingviya, P. Pathaburee, B. Tangtrakulwanich. Inhibitory effects of vancomycin and fosfomycin on methicillin-resistant Staphylococcus aureus from antibiotic-impregnated articulating cement spacers. Bone Joint Res 2017;6:132–136. DOI: 10.1302/2046-3758.63.2000639

Complex acetabular reconstruction for oncology and bone loss are challenging for surgeons due to their often hostile biological and mechanical environments. Titrating concentrations of silver ions on implants and alternative modes of delivery allow surgeons to exploit anti-infective properties without compromising bone on growth and thus providing a long-term stable fixation. We present a case series of 12 custom acetabular tri-flange and custom hemipelvis reconstructions (Ossis, Christchurch, New Zealand), with an ultrathin plasma coating of silver particles embedded between layers of siloxane (BioGate HyProtect™, Nuremberg, Germany). At the time of reporting no implant has been revised and no patient has required a hospital admission or debridement for a deep surgical site infection. Routine follow up x-rays were reviewed and found 2 cases with loosening, both at their respective anterior fixation. Radiographs of both cases show remodelling at the ilium indicative of stable fixation posteriorly. Both patients remain asymptomatic. 3 patients were readmitted for dislocations, 1 of whom had 5 dislocations within 3 weeks post-operatively and was immobilised in an abduction brace to address a lack of muscle tone and has not had a revision of their components. Utilising navigation with meticulous implant design and construction; augmented with an ultrathin plasma coating of silver particles embedded between layers of siloxane with controlled and long-term generation of silver ion diffusion has led to outstanding outcomes in this series of 12 custom acetabular and hemipelvis reconstructions. No patients were revised for infection and no patients show signs of failure of bone on growth and incorporation. Hip instability remains a problem in these challenging mechanical environments and we continue to reassess our approach to this multifaceted problem