Distal femoral osteotomy is an established successful procedure which can delay the progression of arthritis and the need for knee arthroplasty. The surgery, however, is complex and lengthy and consequently it is generally the preserve of highly experienced specialists and thus not widely offered. Patient specific instrumentation is known to reduce procedural complexity, time, and surgeons’ anxiety levels1 in proximal tibial osteotomy procedures. This study evaluated a novel patient specific distal femoral osteotomy procedure (Orthoscape, Bath, UK) which aimed to use custom-made implants and instrumentation to provide a precision correction while also simplifying the procedure so that more surgeons would be comfortable offering the procedure. Three patients (n=3) with early-stage knee arthritis presented with valgus malalignment, the source of which was predominantly located within the distal femur, rather than intraarticular. Using conventional techniques and instrumentation, distal femoral knee osteotomy cases typically require 1.5–2 hours surgery time. The use of bi-planar osteotomy cuts have been shown to improve intraoperative stability as well as bone healing times2. This normally also increases surgical complexity; however, multiple cutting slots can be easily incorporated into patient specific instrumentation.Abstract
Background
Presenting problem
Stratification is required to ensure that only those patients likely to benefit, receive Autologous Chondrocyte Implantation (ACI); ideally by assessing a biomarker in the blood. This study aimed to assess differences in the plasma proteome of individuals who respond well or poorly to ACI. Isobaric tag for relative and absolute quantitation (ITRAQ) mass spectrometry and label-free proteomics analyses were performed in tandem as described previously by our group (Hulme et al., 2017; 2018; 2021) using plasma collected from ACI responders (n=10) compared with non-responders (n=10) at each stage of surgery (Stage I, cartilage harvest and Stage II, cell implantation). iTRAQ using pooled plasma detected 16 proteins that were differentially abundant at baseline in ACI responders compared with non-responders (n=10) (≥±2.0 fold; p<0.05). Responders demonstrated a mean Lysholm (patient reported functional score from 0–100) improvement of 33±13 and non-responders a mean worsening of −13±13 points. The most pronounced plasma proteome shift was seen in response to Stage I surgery in ACI non-responders, with 48 proteins being differentially abundant between the two surgical procedures. We have previously noted this marked shift in response to initial surgery in the SF of ACI non-responders, several of these proteins were associated with the Acute Phase Response. One of these proteins, clusterin, could be confirmed in patients’ plasma using an independent immunoassay using individual samples. Label-free proteomic data from individual samples identified only cartilage acidic protein-1 (known to associate with osteoarthritis progression) to be significantly more abundant at Stage I in the plasma of non-responders. This study indicates that proteins can be identified within the plasma that have potential use in ACI patient stratification. Further work is required to validate the findings of this discovery-phase work in larger ACI cohorts.
The objectives of the study were to investigate demographic, injury and surgery/treatment-associated factors that could influence clinical outcome, following Autologous Chondrocyte Implantation (ACI) in a large, “real-world”, 20 year longitudinally collected clinical data set. Multilevel modelling was conducted using R and 363 ACI procedures were suitable for model inclusion. All longitudinal post-operative Lysholm scores collected after ACI treatment and before a second procedure (such as knee arthroplasty but excluding minor procedures such as arthroscopy) were included. Any patients requiring a bone graft at the time of ACI were excluded. Potential predictors of ACI outcome explored were age at the time of ACI, gender, smoker status, pre-operative Lysholm score, time from surgery, defect location, number of defects, patch type, previous operations, undergoing parallel procedure(s) at the time of ACI, cell count prior to implantation and cell passage number. The best fit model demonstrated that for every yearly increase in age at the time of surgery, Lysholm scores decreased by 0.2 at 1-year post-surgery. Additionally, for every point increase in pre-operative Lysholm score, post-operative Lysholm score at 1 year increased by 0.5. The number of cells implanted also impacted on Lysholm score at 1-year post-op with every point increase in log cell number resulting in a 5.3 lower score. In addition, those patients with a defect on the lateral femoral condyle (LFC), had on average Lysholm scores that were 6.3 points higher one year after surgery compared to medial femoral condyle (MFC) defects. Defect grade and location was shown to affect long term Lysholm scores, those with grade 3 and patella defects having on average higher scores compared to patients with grade 4 or trochlea defects. Some of the predictors identified agree with previous reports, particularly that increased age, poorer pre-operative function and worse defect grades predicted poorer outcomes. Other findings were more novel, such as that a lower cell number implanted and that LFC defects were predicted to have higher Lysholm scores at 1 year and that patella lesions are associated with improved long-term outcomes cf. trochlea lesions.
Conventional proximal tibial osteotomy is a widely successful joint-preserving treatment for osteoarthritis; however, conventional procedures do not adequately control the posterior tibial slope (PTS). Alterations to PTS can affect knee instability, ligament tensioning, knee kinematics, muscle and joint contact forces as well as range of motion. This study primarily aimed to provide a comprehensive investigation of the variables influencing PTS during high tibial osteotomy using a 3D surgical simulation approach. Secondly, it aimed to provide a simple means of implementing the findings in future 3D pre-operative planning and /or clinically. The influence of two key variables: the gap opening angle and the hinge axis orientation on PTS was investigated using three independent approaches: (1) 3D computational simulation using CAD software to perform virtual osteotomy surgery and simulate the post-operative outcome. (2) Derivation of a closed-form mathematical solution using a generalised vector rotation approach (3) Clinical assessment of synthetically generated x-rays of osteoarthritis patients (n=28; REC reference: 17/HRA/0033, RD&E NHS, UK) for comparison against the theoretical/computational approaches. The results from the computational and analytical assessments agreed precisely. For three different opening angles (6°, 9° and 12°) and 7 different hinge axis orientations (from −30° to 30°), the results obtained were identical. A simple analytical solution for the change in PTS, ΔPs, based on the hinge axis angle, α, and the osteotomy opening angle, θ, was derived: ΔPs=sin-1(sin α sin θ) The clinical assessment demonstrated that the absolute values of PTS, and changes resulting from various osteotomies, matched the results from the two relative prediction methods. This study has demonstrated that PTS is impacted by the hinge axis angle and the extent of the osteotomy opening angle and provided computational evidence and analytical formula for general use.
Stratification is required to ensure that only patients likely to benefit, receive Autologous Chondrocyte Implantation (ACI). At Stage I (SI), healthy cartilage is harvested from the joint and chondrocytes culture expanded before being implanted into a chondral/osteochondral defect at Stage II (SII). In ACI non-responders, there is a marked shift in the profile and abundance of proteins detectable in the synovial fluid (SF) at SII, many being associated with an acute phase response (APR). However, clinical biomarkers are easier to measure in blood than SF, so we have now performed this investigation in plasma. Isobaric tag for relative and absolute quantitation mass-spectrometry was used to assess the proteome in plasma pooled from ACI responders (mean Lysholm improvement of 33, n=10) or non-responders (mean: −13 points, n=10), collected at SI or SII surgeries. Interactome networks were generated using STRING. Plasma proteome data were compared to matched SF data, previously analysed, to identify any proteins that changed across the fluids. Clusterin concentration was quantitated (ELISA; Biotechne).Abstract
Purpose
Methods
In the human knee, the cells of the articular cartilage (AC) and subchondral bone (SB) communicate via the secretion of biochemical factors. Chondrocyte-based AC repair strategies, such as articular chondrocyte implantation, are widely used but there has been little investigation into the communication between the native SB cells and the transplanted chondrocytes. We hypothesise that this communication depends on the health state of the SB and could influence the composition and quality of the repair cartilage. An indirect co-culture model was developed using transwell inserts, representing a chondrocyte/scaffold-construct for repair of AC defects adjoining SB with varying degrees of degeneration. Donor-matched populations of human bone-marrow derived mesenchymal stromal cells (BM-MSCs) were isolated from the macroscopically and histologically best and worst osteochondral tissue, representing “healthy” and “unhealthy” SB. The BM-MSCs were co-cultured with normal chondrocytes suspended in agarose, with the two cell types separated by a porous membrane. After 0, 7, 14 and 21 days, chondrocyte-agarose scaffolds were assessed by gene expression and biochemical analyses.Abstract
Objectives
Methods
Meniscus allograft and synthetic meniscus scaffold (Actifit®) transplantation have shown promising outcomes for symptoms relief in patients with meniscus deficient knees. Untreated chondral defects can place excessive load onto meniscus transplants and cause early graft failure. We hypothesised that combined ACI and allograft or synthetic meniscus replacement might provide a solution for meniscus deficient individuals with co-existing lesions in cartilage and meniscus. We retrospectively collected data from 17 patients (16M, 1F, aged 40±9.26) who had ACI and meniscus allograft transplant (MAT), 8 patients (7M, 1F, aged 42±11) who underwent ACI and Actifit® meniscus scaffold replacement. Other baseline data included BMI, pre-operative procedures and cellular transplant data. Patients were assessed by pre-operative, one-year and last follow-up Lysholm score, one-year repair site biopsy, MRI evaluations.Abstract
Objectives
Methods
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. 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.Abstract
Objectives
Methods
Primary cilia are singular structures containing a microtubule-based axoneme which are believed to not only be mechanosensitive but also to co-ordinate many cell functions via signalling pathways including Hedgehog and Wnt. Primary cilia have previously been described on cells of mouse intervertebral discs (IVDs), but not in bovine or human IVDs. Our aim was to examine primary cilia in these species. Nucleus pulposus cells were obtained from cows with no overt disc degeneration and patients following spine surgery (for herniations and/or degenerative disc disease) and cultured until confluent before maintaining with or without serum for 24h. Primary cilia were visualised with antibodies to the axoneme (acetylated α-tubulin and Arl13b) and/or the basal body (pericentrin) using fluorescent secondary antibodies and ≥200 cells per sample were counted.Introduction
Methods
The arcOGEN study identified the 9q33.1 locus as associated with hip osteoarthritis (OA) in females. TRIM32 lies within this locus and may have biological relevance to OA; it encodes a protein with E3 ubiquitin ligase activity. Sanger sequencing of TRIM32 in the youngest 500 female patients with hip OA from the arcOGEN study identified genetic polymorphisms in the proximal promoter, and 3'untranslated region of TRIM32 that are disproportionately represented in female patients with hip OA compared to the control population. Reduced expression of TRIM32 was identified in femoral head articular chondrocytes from patients with hip OA compared to control patients. Trim32 knockout resulted in increased aggrecanolysis in murine femoral head explants. Murine chondrocytes deficient in Trim32 exhibited increased expression of mature chondrocyte markers following anabolic cytokine stimulation, and increased expression of hypertrophic chondrocyte markers following catabolic cytokine stimulation. Trim32 knockout mice demonstrated increased cartilage degradation and tibial subchondral bone changes after surgically-induced knee joint instability. Increased cartilage degradation and medial knee subchondral bone changes were also identified in aged Trim32 knockout mice. These results further implicate TRIM32 in the genetic predisposition to OA, and indicate a role for TRIM32 in the joint degeneration evident in OA. These results support the further study of TRIM32 in the pathophysiology of OA and development of novel therapeutic strategies to manage OA.
The current study aims to ascertain the outcome of ACI with simultaneous transplantation of an autologous bone plug for the restoration of osteoarticular defects in the femoral condyle of the knee (‘Osplug’ technique). Seventeen patients (mean age of 27±7 years), twelve with Osteochondritis dissecans (OD) and five with an osteochondral defect (OCD) was treated with unicortical autologous bone graft combined with ACI (‘Osplug’ technique). Functional outcome was assessed with Lysholm scores obtained for 5 years post-operatively. The repair site was evaluated with the Oswestry Arthroscopy Score (OAS), MOCART MRI score and ICRS II histology score. The mean defect size was 4.5±2.6 SD cm² and mean depth was 11.3±5 SD mm. A significant improvement of Lysholm score from 45 (IQR 24, range 16–79) to 77 (IQR 28, range 41–100) at 1 year (p-value 0.001) and 70 (IQR 35, range 33–91) at 5 years (p-value 0.009). The mean OAS of the repair site was 6.2 (range 0–9) at a mean of 1.3 years. The mean MOCART score was 61 ± 22SD (range 20–85) at 2.6 ± 1.8SD years. Histology demonstrated generally good integration of the repair cartilage with the underlying bone. Poor lateral integration of the bone graft on MRI and low OAS were significantly associated with a poor outcome and failure. The Osplug technique shows significant improvement of functional outcome for up to 5 years. This is the first report describing the association of bone graft integration with functional outcome after such a procedure.
To assess outcomes of manipulating upper extremity fractures with conscious sedation compared with formal reduction and casting in theatre under general anaesthesia and image intensifier control. Prospective six month period all patients presenting to the Emergency Department with a both bone forearm or distal radial fracture that was deemed suitable for closed reduction and casting where included in the study. All fractures deemed to require instrumentation were excluded.Purpose
Method
Structural and functional outcome of bone graft with first or second generation autologous chondrocyte implantation (ACI) in osteochondral defects has not been reported. Seventeen patients (mean age of 27±7 years, range 17–40), twelve with osteochondritis dissecans (OD) (ICRS Grade 3 and 4) and five with isolated osteochondral defect (OCD) (ICRS Grade 4) were treated with a combined implantation of a unicortical autologous bone graft with ACI (the Osplug technique). Functional outcome was assessed with Lysholm scores. The repair site was evaluated with the Oswestry Arthroscopy Score (OAS), MOCART score and ICRS II histology score. Formation of subchondral lamina and lateral integration of the bone grafts were evaluated from MRI scans.Background
Methods
Our aim is to investigate the role of TRIM32 in human and murine articular tissue. TRIM32 expression in human articular cartilage was examined by immunostaining. TRIM32 expression was compared in femoral head chondrocytes from patients with and without primary hip OA (n=6/group) and examined by Western blotting. Aggrecanolysis by femoral head explants from TRIM32 expression was demonstrated in human articular cartilage; TRIM32 expression by chondrocytes was reduced in patients with hip OA (p=0.03). Greater aggrecanolysis occurred in cartilage explants from T32KO mice after treatment with no stimulation (p=0.03), IL1α (p=0.02), and RA (p=0.001). Unstimulated T32KO chondrocytes expressed reduced These results indicate that altered TRIM32 expression in human articular tissue is associated with OA, and that
By the end of training, every registrar is expected to demonstrate proficiency in total knee replacement (TKR). It is unclear whether functional outcomes for knee arthroplasty performed by training grade doctors under supervision of a consultant have equivalent functional outcomes to those performed by consultants. This study investigated the functional outcomes following TKR in patients operated on by a supervised orthopaedic trainee compared to a consultant orthopaedic surgeon. Patients undergoing surgery by a consultant (n=491) or by a trainee under supervision (n=145) between 2003 and 2006 were included. There was a single implant, approach and postoperative rehabilitation regime. Patients were reviewed eighteen months, three years and five years postoperatively. There were no significant differences in preoperative patient characteristics between the groups. There was no difference in length of stay or transfusion or tourniquet time. Both consultant (p<0.001) and trainee (p<0.001) groups showed significant improvement in AKSK and AKSF scores between preoperative and 18 month review and there was no difference in the magnitude of observed improvement between groups (AKSK p=0.853; AKSF p=0.970). There were no significant differences in either score between the groups preoperatively or at any review point postoperatively. At five years postoperative, both groups had a median OKS of 34 (p=0.921). This is the largest reported series of outcomes following primary TKR examining functional outcome linked with grade of surgeon. It shows that a supervised trainee will achieve comparable functional outcomes at up to 5 years post operatively.
Paget's disease of bone (PDB) is the second most common metabolic bone disease. Osteoarthritis (OA) affects one-third of patients with PDB. The incidence of THR (total hip replacement) and TKR (total knee replacement) is 3.1- and 1.7-fold higher in PDB patients compared to non-affected age-matched controls. No large studies or joint registry reports exist describing the outcomes following THR or TKR in patients with PDB. The objectives of this study were to investigate the outcomes following THR and TKR in patients with PDB using national joint registry data. 144 THR and 43 TKR were identified using the Scottish Arthroplasty Project from 1996–2013. For THR, the most common early post-operative surgical complications were haematoma formation (1.4%), and surgical site infection (1.4%). The absolute incidence during follow-up of dislocation was 2.8%, and revision hip arthroplasty was performed in 2.8% of cases. Implant survival of the primary prosthesis was 96.3% (CI: 92.8 – 99.8) at 10-years, and patient survival was 50.0% (39.6 – 60.4) at 10-years. For TKR, the most common early post-operative surgical complication was surgical site infection (2.3%). The absolute incidence during follow-up of revision knee arthroplasty was 4.7%. On survival analysis, implant survival of the primary prosthesis was 94.5% (CI: 87.1 – 100) at 10-years, and patient survival was 38.3% (16.7 – 59.9) at 10-years. This is the largest reported series of outcomes following primary THR and TKR in patients with PDB. PDB patients are not at increased risk of surgical complications following primary THR or TKR compared to non-PDB patients.
The natural history of primary anterior glenohumeral dislocation in adolescent patients remains unclear and no consensus exists for management of these patients. The study objectives were to report the natural history following primary anterior glenohumeral joint dislocation in adolescent patients and to identify risk factors for repeat dislocation. We reviewed prospectively-collected clinical and radiological data of 133 adolescent patients (mean age 16.3 years (range 13–18); 115 male patients (86.5%)) diagnosed with primary anterior glenohumeral joint dislocation and managed nonoperatively from 1996 to 2008 at our institution (mean follow-up 95.2 months (range 1–215)). During follow-up, 102 (absolute incidence of 76.7%) patients experienced repeat dislocation. Median time interval between primary and repeat dislocation was 10 months (CI: 7.4 – 12.6). On survival analysis, 59% (CI: 51.2 – 66.8%) of patients remained stable one year following initial injury, 38% (CI: 30.2 – 45.8%) after two years, 21% (CI: 13.2- 28.8%) after five years, and 7% (CI: 1.1–12.9%) after 10 years. Neither age nor gender significantly predicted repeat dislocation during follow-up. In conclusion, adolescent patients with primary anterior glenohumeral joint dislocations have a high rate of repeat dislocation, which usually occurs within two years of initial injury, and these patients should be considered early for operative stabilisation.
Antimicrobial resistance is an important patient safety issue. Antibiotic Stewardship is one of the key strategies in tackling this problem. We present our data over a two year period from October 2011 to December 2013. A multidisciplinary, consultant led antibiotic ward round was implemented in October 2011. This involved the consultant orthopaedic surgeon, microbiologist, pharmacist and antibiotic prescription nurse. Data from the meetings was collected prospectively over a 118 week period using a standard data form. The case notes, prescription kardex, laboratory results including microbiology data and clinical information of patients was available at the time of the Ward round. The indications for, choice of antibiotics, duration and further treatment plan were made and a note for the case notes was dictated immediately. Changes to prescriptions were also made at the time.Introduction:
Method:
The treatment of acute rupture of the tendo-achilles remains controversial. There is good evidence to suggest that outcomes are the same for both operative and non-operative treatment when a functional rehabilitation program is utilised. However, debate continues as to whether the radiological gap-size between the proximal and distal remnants of the tendon has an influence on the suitability for non-operative management. All adult patients who attended the emergency department with a clinically suspected tendo-achilles rupture were place in a plantarflexed cast, and underwent MRI scanning to confirm the diagnosis. They were then counselled on the risks and benefits of operative versus non-operative treatment. Patients opting for non-operative treatment were asked to take part in the study and treated using a functional rehabilitation programme. Gap sizes were determined using a standardised protocol by a single musculoskeletal radiologist blinded to the clinical outcomes.Introduction:
Methods:
Randomised controlled study evaluating new bone formation Regenerating new bone by cell therapy could provide therapeutic options in many conditions such as fracture non-unions and osteo-chondral defect regeneration in advance OA. In this randomised controlled study we evaluated the efficacy of new bone formation by bone marrow derived stromal cells (BMSC) in patients with non-union.Summary
Introduction
