Summary Statement. The current study introduced the effects of
Abstract. OBJECTIVE. Changes in subchondral bone are one of few disease characteristics to correlate with pain in OA. 1. Profound neuroplasticity and nociceptor sprouting is displayed within osteoarthritic (OA) subchondral bone and is associated with pain and pathology. 2. The cause of these neural changes remains unestablished. Correct innervation patterns are indispensable for bone growth, homeostasis, and repair. Axon guidance signalling factor, Sema3A is essential for the correct innervation patterning of bony tissues. 3. , expressed in osteocytes. 4. and known to be downregulated in bone OA mechanical loading. 5. Bioinformatic analysis has also shown Sema3a as a differentially expressed pathway by bone in human OA patients. 6. HYPOTHESIS: Pathological mechanical load and inflammation of bone causes dysregulation of Sema3A signalling leading to perturbed sensory nerve plasticity and pain. METHODS. Human KOLF2-C1 iPSC derived nociceptors were generated by TALEN-mediated insertion of transcription factors NGN2+Brn3A and modified chambers differentiation protocol to produce nociceptor-like cells. Nociceptor phenotype was confirmed by immunocytochemistry. Human Y201-MSC cells were embedded in 3D type-I collagen gels (0.05 × 106 cell/gel), in 48-well plates and silicone plates, were differentiated to osteocytes for 7 days before stimulation with IL-6 (5ng/ml) and soluble IL-6 receptor (sIL-6r (40ng/ml), IL6/sIL6r and mechanical load mimetic Yoda1 (5μM) or unstimulated (n=5/group) (48-well plates) or were mechanically loaded in silicone plates (5000μstrain, 10Hz, 3000 cycles) or not loaded (n=5/group). Conditioned media transfer was performed from osteocyte to nociceptor cultures assessed by continuous 24-hour phase contrast confocal microscopy. 24-hours after stimulation RNA was quantified by RT-qPCR (IL6) or RNAseq whole transcriptome analysis/DEseq2 analysis (Load). Protein release was quantified by ELISA. Normally distributed data with homogenous variances was analysed by two-tailed t test. RESULTS. IPSC-derived nociceptor-like cells display elongated (>5mm) dendritic
Osteotomies in the musculoskeletal system are joint preserving procedures to correct the alignment of the patient. In the lower limb, most of the pre-operative planning is performed on full leg weightbearing radiographs. However, these images contain a 2-dimensional
Unicompartmental knee arthroplasty (UKA) is associated with a higher risk of revision compared with total knee arthroplasty (TKA). The outcomes of knee arthroplasty are typically presented as implant survival or incidence of revision after a set number of years, which can be difficult for patients and clinicians to conceptualise. We aimed to calculate the ‘lifetime risk’ of revision for UKA as a more relatable estimate of risk
Though dentin matrix protein 1 (Dmp1) is known to play critical role in mediating bone mineralization, it has also been validated to be expressed in brain and helps maintain blood brain barrier (BBB). Our study aims to clarify the expression pattern of Dmp1 in mouse brain and explore whether intercellular mitochondrial transfer occurs between Dmp1 positive astrocytes (DPAs) and endothelial cells, and thus acting as a mechanism in maintaining BBB during aging. Single cell RNA sequencing (scRNAseq) of 1 month, 6 month, and 20 month old mice brain (n=1, respectively) was employed to identify Dmp1 positive cell types. Dmp1. Cre. -mGmT and Dmp1. Cre. -COX8a fluorescent mice were generated to visualize DPAs and investigate their mitochondrial activities. A 3D noncontact coculture system and mitochondrial transplantation were applied to study the role of mitochondrial transfer between astrocytes and bEnd.3 endothelial cells. Dmp1. Cre. -Mfn2. f/f. mice were generated by depleting the ER-mitochondria tethering protein Mfn2 in DPAs. Dmp1 was mainly expressed in astrocytes at different ages. GO analysis revealed that cell
The purpose of this study is to report the clinical and radiological outcomes of patients undergoing primary or revision reverse total shoulder arthroplasty using custom 3D printed components to manage severe glenoid bone loss with a minimum of 2-year follow-up. After ethical approval (reference: 17/YH/0318), patients were identified and invited to participate in this observational study. Inclusion criteria included: 1) severe glenoid bone loss necessitating the need for custom implants; 2) patients with definitive glenoid and humeral components implanted more than 2 years prior; 3) ability to comply with patient reported outcome questionnaires. After seeking consent, included patients underwent clinical assessment utilising the Oxford Shoulder Score (OSS), Constant-Murley score, American Shoulder and Elbow Society Score (ASES), and quick Disabilities of the Arm, Shoulder, and Hand Score (quickDASH). Radiographic assessment included AP and axial
Introduction and Objective. Up to 30% of thoracolumbar (TL) fractures are missed in the emergency room. Failure to identify these fractures can result in neurological injuries up to 51% of the casesthis article aimed to clarify the incidence and risk factors of traumatic fractures in China. The China National Fracture Study (CNFS. Obtaining sagittal and anteroposterior radiographs of the TL spine are the first diagnostic step when suspecting a traumatic injury. In most cases, CT and/or MRI are needed to confirm the diagnosis. These are time and resource consuming. Thus, reliably detecting vertebral fractures in simple radiographic
Introduction and Objective. Joint malleolar fractures have been estimated around 9% of all fractures. They are characterized by different both early and late complications. Among the latter, arthrofibrosis and early secondary arthrosis represent the two most common ones. Moreover, these two complications could be considered related to each other. Their real cause is still under investigation, even if residual post-operative hematoma and acute post-traumatic synovitis appear to be the most accredited. Supporting this hypothesis, joint debridement and the evacuation of the post-operative hematoma could represent a possible solution. The aim of this prospective study is to evaluate the role of arthroscopic lavage and debridement during internal fixation in order to prevent late joint complications. Materials and Methods. Sixty consecutive patients who reported dislocated articular ankle fractures with surgical indication of open reduction and internal fixation (ORIF) have been included in this study. 27 patients underwent ORIF surgery associated with arthroscopic washout and debridement, while 33 patients, representing the control group, underwent just internal reduction and osteosynthesis. Patients with pure dislocations, non-articular fractures, polytrauma, previous local trauma, metabolic and connective pathologies were excluded. Follow-up was performed at 40 days (T1), 3 (T2) and 6 months (T3) after trauma for all patients. If necessary, some have been re-evaluated 12 months after the trauma. Efficacy of the treatment was evaluated through the VAS scale, Maryland scale, search for local complications such as dehiscence or infections, and finally radiographic evaluation. T-Student was estimated in order to individuate statistical significance. Results. VAS scale showed higher values for the case group than the control group with mean values of 2.7 and 4.2 at T1 and 2.1 and 3.8 at T2, respectively. At 6 months follow-up, the VAS values resulted similar with 2.6 for the case group and 2.8 for the control group. The same
Abstract. Background. Accurate analysis of the patellar resurfacing is essential to better understand the etiology of patella-femoral problems and dissatisfaction following total knee arthroplasty (TKA). In the current published literature patellar resurfacing is analysed using 2D radiographs. With use of radiographs there is potential for error due to differences in limb positioning,
Objectives. The Attune total knee arthroplasty (TKA) has been used in over 600 000 patients worldwide. Registry data show good clinical outcome; however, concerns over the cement-tibial interface have been reported. We used retrieval analysis to give further insight into this controversial topic. Methods. We examined 12 titanium (Ti) PFC Sigma implants, eight cobalt-chromium (CoCr) PFC Sigma implants, eight cobalt-chromium PFC Sigma rotating platform (RP) implants, and 11 Attune implants. We used a peer-reviewed digital imaging method to quantify the amount of cement attached to the backside of each tibial tray. We then measured: 1) the size of tibial tray thickness, tray
The understanding of rotational alignment of the distal femur is essential in total knee replacement to ensure that there is correct placement of the femoral component. Many reference axes have been described, but there is still disagreement about their value and mutual angular relationship. Our aim was to validate a geometrically-defined reference axis against which the surface-derived axes could be compared in the axial plane. A total of 12 cadaver specimens underwent CT after rigid fixation of optical tracking devices to the femur and the tibia. Three-dimensional reconstructions were made to determine the anatomical surface points and geometrical references. The spatial relationships between the femur and tibia in full extension and in 90° of flexion were examined by an optical infrared tracking system. After co-ordinate transformation of the described anatomical points and geometrical references, the
Abstract. OBJECTIVE. Flattening of the talar dome is observed clinically in haemarthropathy as structural and functional changes advance but has not been quantified yet. In order to confirm clinical observation, and assess the degree of change, morphological measurements were derived from MR images. METHODS. Four measurements were taken, using ImageJ (1.52v), from sagittal MRI
The incidence of osteoarthritis (OA) is increasing in our younger population. OA development early in life is often related to cartilage damage, caused by (sport) injury or trauma. Detection of early knee OA is therefore crucial to target early treatment. However, early markers for OA prognosis or diagnosis are lacking. Hoffa's fat pad (HFP) is an emerging source for knee biomarkers, as it is easily accessible and shows important interaction with the homeostasis of the knee. In this study, we used Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) as a first approach. MALDI-MSI allows the study of tissue-specific molecular distributions. Therefore, we used MALDI-MSI to analyze the lipid profiles in the HFP of three patients with OA and three patients undergoing cartilage regenerative treatment. We demonstrate that the lipid profile of patients with OA is different from patients with cartilage defects. HFP of each patient were snap frozen directly after surgical resection and cryosectioned at 15 μm. Each slide was sublimed with Norharmane matrix and analyzed by MALDI-MSI in positive and negative ion modes at a lateral resolution of 50 μm on a RapifleX Tissue Typer. The difference between patient groups were analyzed using principle component analysis and linear discriminant analysis. Lipid identifications were obtained on an Orbitrap Elite™ Hybrid Ion Trap-Orbitrap Mass Spectrometer in data dependent acquisition mode and analyzed using Lipostar software. Linear discriminant analysis showed a specific lipid profile for each group (variance 33.94%). Score
The CCI mobile bearing ankle implant used at our orthopedic department 2010–2013, was abandoned due to failures and findings of bone loss at revision. The aim of this study was to a) Determine our true revision rate, b) Investigate accuracy of measuring prevalence, size and location of periprosthetic bone cysts through X-ray and CT and c) Relate these findings to implant alignment and patient reported outcome measurements (PROMs). 51 primary surgeries were performed, prior to this study 8 had been revised. Out of 43 un-revised patients, 36 were enrolled and underwent evaluation with metal artefact reduction CT-scans and conventional X-ray. They filled out 3 PROMs; SEFAS, SF-12, EQ-5D. Cyst volume larger than 0.1 ml was measured using VITREA volume tools for CT-scans and calculation of spherical volume for X-rays; using AP- and lateral
Background. Despite an ageing population and a rise in the number of joint replacements being performed, the mean age of patients undergoing surgery remains static. One explanation for this is continued concern over the risks of performing surgery on the very elderly. We aim to investigate the outcome of Total Knee Replacement (TKR) in a nonagenarian population. Methods. The Elective Orthopaedic Centre, Epsom has an established patient reported outcome measures (PROMs) programme into which all patients are routinely enrolled. We retrospectively reviewed our data set for a cohort of nonagenarians undergoing primary TKR, between April 2008 and October 2011. Post-operative complications, mortality rates and functional outcomes were compared to those of a time matched 70–79 year old cohort. Only patients with a primary diagnosis of osteoarthritis were included whereas an exclusion criterion consisted of patients undergoing revision surgery, simultaneous bilateral replacements or conversion from a Unicompartmental Knee replacement. Results. We identified 31 nonagenarian patients, with a mean age of 91.0 (90–96) and the control group consisted of 36 patients, with a mean age of 74.5 (70–79). Following a TKR, the nonagenarian cohort achieved a lower mean Oxford Knee Score (OKS) at 1 year (31.7+/−9.5) (p=0.15), but no difference existed by 2 years (p=0.157), and a mean outcome satisfaction of 85.2% (+/− 22.75) at 1 year, which was similar to the younger group. The nonagenarians had a greater risk of requiring a blood transfusion following a TKR (p=0.0373; CI 1.08 to 16.65), and a longer length of stay than their younger counterparts (p=0.001). Mortality rates were higher in the nonagenarian cohort, but these were in keeping with the life expectancy
Patellofemoral pain syndrome (PFPS) is a common knee disorder in active individuals. Movement dysfunction of valgus positioning at the knee during weight-bearing is frequently seen in PFPS. A single-leg squat (SLS) is a test commonly used in physiotherapy to assess for movement dysfunction. Kinesio-Tape (KT) is gaining in popularity in treating PFPS and claims to alter muscle recruitment and motor control, however evidence is weak. Objective: To evaluate the effect of KT applied to the quadriceps on muscle activity with electromyography (EMG) of the rectus femoris, vastus lateralis and vastus medialis oblique and motor control via the frontal plane
Objectives. To assess the clinical and cost-effectiveness of a virtual fracture clinic (VFC) model, and supplement the literature regarding this service as recommended by The National Institute for Health and Care Excellence (NICE) and the British Orthopaedic Association (BOA). Methods. This was a retrospective study including all patients (17 116) referred to fracture clinics in a London District General Hospital from May 2013 to April 2016, using hospital-level data. We used interrupted time series analysis with segmented regression, and direct before-and-after comparison, to study the impact of VFCs introduced in December 2014 on six clinical parameters and on local Clinical Commissioning Group (CCG) spend. Student’s t-tests were used for direct comparison, whilst segmented regression was employed for
Background. Recent studies have suggested that full-limb radiographs are more accurate and sensitive than short film radiographs for pre-operative measurement of the anatomical angles required to achieve optimal knee alignment in Total Knee Arthroplasty (TKA). However, there are drawbacks associated with their use including excess radiation to the pelvic organs, the need for specialised radiography equipment and increased cost. Given these drawbacks, we compared the use of MRI scans, a commonly performed pre-operative investigation, with short film knee radiographs for measurement of knee alignment. Objective. To investigate whether knee alignment measurements made on MRI scans correlate with those measured on short film knee radiographs in patients with osteoarthritic knees. Methods. We retrospectively reviewed short film knee radiographs and MRI scans of 50 patients with knee osteoarthritis. The plain radiographs had to be performed whilst weight bearing. The MRI scans were performed supine and non-weight bearing. The exclusion criteria included previous trauma to the knee, previous TKA and previous fracture of the lower limb. 4 angle measurements defined by The American Knee Society: alpha, beta, sigma and gamma were measured using each of the 2 modalities. Kolmogorov-Smirnov and two- tailed paired t-tests were used for statistical analysis of the results. Pearson correlation coefficient was used for the measure of dependence. Results. The alpha, beta, sigma and gamma angles obtained using the MR images were different to those obtained using short film weight bearing knee radiographs by −3°± 1° (p < 0.001), 1° ± 3° (p=0.002), 1° ± 3° (p=0.047) and 1° ± 4° (p=0.113) respectively. There was a weak correlation between the MRI based method and the radiographic method in measuring all 4 angles. Conclusions. Our results have shown that the angular measurements performed on MR images should be interpreted with caution as they may vary depending on the MRI slice selected for evaluation. The differences observed and the weak correlation between the 2 modalities may be due to the different scopes used for determining the femoral or tibial axes. The measurements obtained using the plain radiographs were interpreted using a single 2D
Anterior-posterior (AP) x-rays are routinely taken following total hip replacement to assess placement and orientation of implanted components. Pelvic orientation at the time of an AP x-ray can influence projected implant orientation. 1. However, the extent of pelvic orientation varies between patients. 2. Without compensation for patient specific pelvic orientation, misleading measurements for implant orientation may be obtained. These measurements are used as indicators for post-operative dislocation stability and range of motion. Errors in which could result in differences between expectations and the true outcome achieved. The aim of this research was to develop a tool that could be utilised to determine pelvic orientation from an AP x-ray. An algorithm based on comparing
In vitro biomechanical tests allow obtaining important information about stresses and deformations inside the bone, and about the displacements of the prosthetic device under physiological load conditions. This information may be helpful for the development of innovative devices, for the improvement of the existing ones, and for defining optimized procedure for bone reconstruction depending on the typology of bone defects. The definition of a robust and reproducible reference frame is the first step in order to perform a consistent biomechanical test [1]. The aims of the current study was to define an anatomical reference frame for pelvis which can also be applied to a hemi-pelvis. A robust alignment method was sought so as to replicate the anatomical pose during in vitro applications. The intra- and inter- operator repeatability was quantified to corroborate the results. The anatomical reference frame was derived from the anterior pelvic plane [2] and was adapted for in vitro applications. It was based on the following anatomical landmarks: Anterior Superior Iliac Spine (ASIS, defined as the most prominent point on the external iliac surface); Posterior Superior Iliac Spine (PSIS) defined as the upper and most prominent