Tendinopathy can commonly occur around the foot and ankle resulting in isolated rupture, debilitating pain and degenerative foot deformity. The pathophysiology and key cells involved are not fully understood. This is partly because the dense collagen matrix that surrounds relatively few resident cells limits the ability of previous techniques to identify and target those cells of interest. In this study, we apply novel single cell RNA sequencing (CITE-Seq) techniques to healthy and tendinopathic foot/ankle tendons. For the first time we have identified multiple sub-populations of cells in human tendons. These findings challenge the view that there is a single principal tendon cell type and open new avenues for further study. Healthy tendon samples were obtained from patients undergoing tendon transfer procedures; including tibialis posterior and FHL. Diseased tendon samples were obtained during debridement of intractable Achilles and peroneal tendinopathy, and during fusion of degenerative joints. Single cell RNA sequencing with surface proteomic analysis identified 10 sub-populations of human tendon derived cells. These included groups expressing genes associated with fibro-adipogenic progenitors (FAPs) as well as ITGA7+VCAM1- recently described in mouse muscle but, as yet, not human tendon. In addition we have identified previously unrecognised sub-classes of collagen type 1 associated tendon cells. Each sub-class expresses a different set of extra-cellular matrix genes suggesting they each play a unique role in maintaining the structural integrity of normal tendon. Diseased tendon harboured a greater proportion of macrophages and cytotoxic lymphocytes than healthy tendon. This inflammatory response is potentially driven by resident tendon fibroblasts which show increased expression of pro-inflammatory cytokines. Finally, identification of a previously unknown sub-population of cells found predominantly in tendinopathic tissue offers new insight into the underlying pathophysiology. Further work aims to identify novel proteins targets for possible therapeutic pathways.
Cam morphology develops during adolescence and predisposes individuals to future hip pain and osteoarthritis. An improved understanding of cam development is required to determine whether the process is modifiable. The aim of this study was to characterise the risk factors, timing, and pathogenesis of cam formation.Background
Hypothesis/Purpose
The appropriate management for patients with a degenerative tear
of the rotator cuff remains controversial, but operative treatment,
particularly arthroscopic surgery, is increasingly being used. Our
aim in this paper was to compare the effectiveness of arthroscopic
with open repair of the rotator cuff. A total of 273 patients were recruited to a randomised comparison
trial (136 to arthroscopic surgery and 137 to open surgery) from
19 teaching and general hospitals in the United Kingdom. The surgeons
used their usual preferred method of repair. The Oxford Shoulder
Score (OSS), two years post-operatively, was the primary outcome
measure. Imaging of the shoulder was performed at one year after
surgery. The trial is registered with Current Controlled Trials,
ISRCTN97804283.Aims
Patients and Methods
A trial-based comparison of the use of resources, costs and quality
of life outcomes of arthroscopic and open surgical management for
rotator cuff tears in the United Kingdom NHS was performed using
data from the United Kingdom Rotator Cuff Study (UKUFF) randomised
controlled trial. Using data from 273 patients, healthcare-related use of resources,
costs and quality-adjusted life years (QALYs) were estimated at
12 months and 24 months after surgery on an intention-to-treat basis
with adjustment for covariates. Uncertainty about the incremental
cost-effectiveness ratio for arthroscopic Aims
Patients and Methods
High failure rates of metal-on-metal hip arthroplasty implants have highlighted the need for more careful introduction and monitoring of new implants and for the evaluation of the safety of medical devices. The National Joint Registry and other regulatory services are unable to detect failing implants at an early enough stage. We aimed to identify validated surrogate markers of long-term outcome in patients undergoing primary total hip arthroplasty (THA). We conducted a systematic review of studies evaluating surrogate markers for predicting long-term outcome in primary THA. Long-term outcome was defined as revision rate of an implant at ten years according to National Institute of Health and Care Excellence guidelines. We conducted a search of Medline and Embase (OVID) databases. Separate search strategies were devised for the Cochrane database and Google Scholar. Each search was performed to include articles from the date of their inception to June 8, 2015.Objectives
Methods
Tendon healing begins with inflammation and results in an incomplete repair with fibrosis, culminating in tendon pathology along with tissue degeneration. Inflammatory mediators regulate the expression of growth factors, and members of the TGFβ superfamily including BMPs have been suggested to play a key role in the development of fibrosis. In established tendon diseases where inflammation and reparative processes persists, the cellular phenotype of tendon cells has been implied to undergo a transformation from that of normal tissue. This study investigates the inflammation-driven mechanisms of tendon pathology using an Diseased human tendon cells were isolated from patients with large to massive rotator cuff tears (n=4). Cells isolated from healthy human hamstring tendons served as control tissue (n=5). Cells were treated with human recombinant IL-1β (5ng/ml), oncostatin M (10ng/ml), IL-6 (10ng/ml), IL-10 (10ng/ml) in serum-free medium, or serum-free medium alone (control) for 24 hours. Cell viability was monitored by Alamar Blue assay, and expression of Introduction
Materials and Methods
The effects of local glucocorticoid on tendon appear broadly negative and this supports the emerging clinical evidence which points toward significant long term harms associated with this treatment modality. The use of locally administered glucocorticoid is widespread in the treatment of painful tendinopathy. Despite evidence of short term benefit, the emerging evidence points toward significant long term harms associated with this method of treatment, including an increased risk of recurrence, rupture and worsened clinical outcomes (1, 2). Our primary purpose was to summarise the known effects of locally administered glucocorticoid on tendon tissue and tendon cells.Summary Statement
Introduction
Dickkopf-3 is upregulated in OA cartilage and synovial tissue. In vitro studies show Dkk3 can prevent cartilage degradation and antagonise Wnt signaling. We hypothesis that Dkk3 can protect against OA-related cartilage destruction. Our group has previously shown that Dkk3, a member of the Dkk family of Wnt antagonists, is upregulated in OA cartilage and synovium. Levels of Dkk3 in synovial fluid are also increased in individuals with tricompartmental OA and after arthroscopy. The role of Dkk3 in cartilage or the factors regulating its expression are not currently understood. Correct regulation of cell signalling pathways is integral to cartilage homeostasis and thus the prevention of OA pathogenesis. Dkk3 is a member of the Dkk family of Wnt antagonists and therefore may impact on chondrocyte biology through interaction with the Wnt pathway. Dkk3 has also been found to influence TGFβ signalling in other cell systems.Summary Statement
Introduction
The aim of this study was to compare patterns (aligned, random and grid) of electrospun polydioxanone scaffolds for tendon repair. The aligned design was optimal, directing cell shape, orientation and protein expression. Moreover, it naturally crimped, presenting tendon-like morphology. Nanofibrous electrospun materials have been previously proposed as potential scaffolds for tendon repair, with emphasis on biomimetic design, postulated to encourage tissue regeneration. In this study, we characterised the interaction of primary tendon-derived cells with polydioxanone (PDO) scaffolds. PDO is a polymer with an excellent Summary Statement
Introduction
The dGEMRIC index correlates more strongly with the pattern of radiographic joint space narrowing in hip osteoarthritis at five year follow-up than morphological measurements of the proximal femur. It therefore offers potential to refine predictive models of hip osteoarthritis progression. Longitudinal general population studies have shown that femoroacetabular impingement increases the risk of developing hip osteoarthritis, however, morphological parameters have a low positive predictive value. Arthroscopic debridement of impingement lesions has been proposed as a potential strategy for the prevention of osteoarthritis, however, the development of such strategies requires the identification of individuals at high risk of disease progression. We investigated whether delayed Gadolinium-Enhanced MRI of Cartilage (dGEMRIC) predicts disease progression. This imaging modality is an indirect measure of cartilage glycosaminoglycan content.Summary
Introduction
The peripheral neuronal phenotype is significantly altered in rotator cuff tendinopathy (RCT) with a clear upregulation of the Glutaminergic system being present in disease. Shoulder pain is the third most frequent cause of chronic musculoskeletal pain in the community and is usually caused by rotator cuff tendinopathy (RCT). The central and peripheral nervous system play an important role in both tissue homoeostasis and tendon healing. The Glutaminergic system is of key importance in driving the peripheral and central neuronal changes which increase the body's sensitivity to pain (1, 2). No study to date has investigated the role of the glutaminergic system in human RCT. We hypothesised that the peripheral neuronal phenotype would be altered in RCT, and would vary according to disease stage as measured by size of tear. The term ‘peripheral neuronal phenotype’ is used to refer to refer to specific characteristics of the peripheral nervous system, neuronal mediators and the receptors for these mediators in peripheral tissueSummary Statement
Introduction
This study describes the design and preliminary in vitro testing of a novel patch for the repair of rotator cuff tendon tears. The laminated design incorporates woven and electrospun components. The woven element provides the patch with excellent mechanical strength and the electrospun layer improves cell attachment and promotes cell orientation and diferentiation. Aligned nanofibrous electrospun scaffolds have been previously proposed as ideal scaffolds for tendon repair, replicating the anisotropy of tendon and providing a biomimetic design to encourage tissue regeneration (Hakimi et al., 2012). However, such scaffolds are still limited in terms of mechanical properties. This paper presents the design of a novel patch for rotator cuff repair in which the electrospun scaffold is supported by a woven component.Summary Statement
Introduction
A novel biomimetic polydioxanone tendon patch with woven and electrospun components is biocompatible, recapitulates native tendon architecture and creates a tissue-healing microenvironment directed by a subpopulation of regenerative macrophages. The woven component provides tensile strength while the tendon heals. There is great interest in the use of biomimetic devices to augment tendon repairs. Ideally, implants improve healing without causing adverse local or systemic reactions. Biocompatibility remains a critical issue prior to implantation into humans, as some implants elicit a foreign body response (FBR) involving inflammation, poor wound healing and even fistulae formation. Additionally, the effect on articular cartilage locally or systemically with placement of a juxta-articular implant has not been examined. The purpose of this study is to test the Summary Statement
Introduction
Subtle deformities of the acetabulum and proximal femur are recognised as biomechanical risk factors for the development of hip osteoarthritis (OA) as well as a cause of hip and groin pain. We undertook this study to examine relationships between a number of morphological measurements of the acetabulum and proximal femur and the hip pain in a 20-year longitudinal study. In 1989 women of 45–64 years of age were recruited. Each had an AP-Pelvis radiograph at Year-2. These radiographs were analysed using a validated programme for measuring morphology. All morphological measurements were read blinded to outcome. At year 3 all participants were asked whether they experienced hip pain (side specific). This was repeated at visits up to and including 20-years. Logistic regression analysis (with robust standard errors and clustering by subject identifier) was performed using hip pain as a binary outcome. The model adjusted for baseline age, BMI and joint space and included only participants who were pain free on initial questioning.Introduction
Methods
There is increasing evidence for a multi-stage model of rotator cuff (RC) tendon tears, wherein healing is affected by tear size. The underlying pathophysiology however is not fully understood. Changes in the production and remodeling of the RC extracellular matrix (ECM) are likely to be important determinants of RC tendinopathy as they affect healing and the ability to bear loads. This study aimed to gain greater insight into size related tear pathogenesis by analyzing gene expression profiles from normal, small and massive RC tears. The genetic profiles of 28 human RC tendons were analyzed using microarrays representing the entire genome. 11 massive and 5 small torn RC tendon specimens were obtained from tear edges intraoperatively, and compared to 12 age matched normal controls. Semiquantitative real-time polymerase chain reaction (RT-PCR) and immunohistochemistry were performed for validation.INTRODUCTION
METHODS
This study describes the prevalence of pain, functional loss and rotator cuff tears (RCTs) in a general population cohort. It is the first multidisciplinary assessment in such a cohort. The Chingford cohort is a 19-year old longitudinal population study comprising 1003 women aged between 44 and 67 at baseline. To date 183 consecutive subjects (366) shoulders have been interviewed about their shoulders. Myometric strength assessment and high-definition ultrasound examination (US) have been performed on all shoulders. Additionally pain thresholds and perceptions of pain have been tested using quantitative sensory testing (QST) and a number of validated questionnaires, including the illness attitudes scale and the pain detect score.INTRODUCTION
METHODS
The pathophysiology of high failure rates following rotator cuff tendon repairs, particularly massive tears, is not fully understood. Collagen structural changes have been shown to alter tendon thermal and mechanical properties. Thermal changes in small biopsies, detected by differential scanning calorimetry (DSC) can help to quantify collagen structural differences in torn rotator cuff tendons. This study aimed to form a quantitative rather than qualitative assessment, of whether differences in collagen structure and integrity existed between small biopsies of normal, small and massive rotator cuff tears using DSC. Thermal properties were measured for 27 human biopsies taken intra-operatively from normal, small, and massive rotator cuff tendon tears. 3 samples were taken from each patient and subjected to a modulated temperature ramp between 20–80°C at a rate of 2°C per minute with 0.318°C amplitude. The melting temperature (TM) is proposed to represent amide-amide hydrogen bond breakage and resulting protein backbone mobility. Denaturing temperature (TD) reportedly corresponds to the temperature at which the proteins fall out of solution. Denaturation enthalpy (H) should correlate with the amount of triple helical structure. Based upon a pre-study power calculation, this study had 90% power to detect a 10% difference in melting and denaturation temperature between groups with alpha=0.05. 1 specimen per patients was also frozen and cryosectioned and polarised light microscopy was used for quantitative validation. The effect of tear size on heat related parameters were performed using a one-way ANOVA test. A student's unpaired t-test was used to search for differences between individual groups (small tears, massive tears and normal tendons).Introduction
Methods
In order to address high failure rates following rotator cuff repairs, a greater understanding is required of the underlying structural changes so that treatments can be appropriately targeted and biomarkers of failure can be identified. As collagen is the primary constituent of tendon and determines force transmission, collagen structural changes may affect responses to loading. For example changes in collagen 1 and 5 are associated with the hyperelastic Ehlers-Danlos syndrome, which is diagnosed by looking for pathopneumonic altered collagen fibres or ‘collagen flowers’ in skin using transmission electron microscopy (TEM). To date no study has been performed on the microstructure of torn human rotator cuff tendons using TEM. It was hypothesized that normal, small and massive human rotator cuff tendons tears will have altered microscopic structures. The unique study aimed to use TEM to compare the ultrastructure of small and massive rotator cuff tears, to normal rotator cuff tendons. Samples from 7 human rotator cuff tendons repairs were obtained, including 4 massive (>5 cm) and 3 small (< 1 cm) tears, and 3 matched normal controls with no history of connective tissue disorders. Specimens were fixed in 4% glutaraldehyde in 0.1M phosphate buffer, processed and examined blind using routine TEM examination. To assess whether changes in the relative expression of collagen 1 and 5 (COL1A1, COL5A1 and COL5A2) occurred in all tears, qPCR was performed on another 6 phenotypically matched patients.INTRODUCTION
METHODS
The Oxford Knee Score (OKS) is a validated and widely used PROM that has been successfully used in assessing the outcome of knee arthroplasty (KA). It has been adopted as the nationally agreed outcome measure for this procedure and is now routinely collected. Increasingly, it is being used on an individual patient basis as a pre-operative measure of osteoarthritis and the need for joint replacement, despite not being validated for this use. The aim of this paper is to present evidence that challenges this new role for the OKS. We have analysed pre-operative and post-operative OKS data from 3 large cohorts all undergoing KA, totalling over 3000 patients. In addition we have correlated the OKS to patient satisfaction scores. We have validated our findings using data published from the UK NJR.Purpose
Method
To investigate the effect of lab-based simulator training, on the ability of surgical trainees to perform diagnostic knee arthroscopy. 20 orthopaedic SHOs with minimal arthroscopic experience were randomised to 2 groups. 10 received a fixed protocol of simulator based arthroscopic skills training using a bench-top knee model. Learning curves were clearly demonstrated using motion analysis equipment to monitor performance. All 20 then spent an operating list with a blinded consultant trainer. They received instruction and demonstration of diagnostic knee arthroscopy before performing the procedure independently. Their performance was assessed using the intra-operative section of the Orthopaedic Competence Assessment Project (OCAP) procedure based assessment (PBA) protocol for diagnostic arthroscopy. Performance was further quantified with a ten point global rating assessment scale.Objective
Method
1030–1200cm-1: carbohydrates, phospholipids, 1300–1700, 3000–3350cm-1: collagen structural conformation and 2800–3000 cm-1: lipids. Partial tears were distinguishable from other stages of tendon pathology based on a spectral region which correlated with collagen III.
The aim of this study was to define normal, borderline, and abnormal parameters for the morphology of the proximal femur, in the context of the cam deformity, by studying asymptomatic individuals with normal clinical examination and no osteoarthritis from the general population.
The aim of this study was to find evidence of tissue hypoxia and apoptosis (programmed cell death) have on a human model of rotator cuff failure. We studied twenty seven patients with no tear mild impingment (3), no tear moderate impingment (3), no tear severe impingment (3), partial tear (3), small tear (3), moderate tear (3), large tear (3), massive tear (3) and control (3) who were undergoing shoulder arthroscopy, subacromial decompression and potential rotator cuff repair. A supraspinatus tendon biopsy was taken during debridement/repair on all cases (ethics number C01.071). Control tendon was obtained from the subscapularis tendon of patients undergoing stabilization surgery. Biopsies were analysed using two immunocytological techniques. A monoclonal antibody against BNIP-3 (a pro-apoptotic marker of hypoxia) and TUNEL (an apoptotic marker). An immunofluorescent nuclear counterstain DAPI (4 6-Diamidino-2-phenylindole dihy-drochloride) was used to stain all cells. Positive cells and total cell number were then counted in 10 high powered fields per section. The results showed a significant increase in BNIP-3 expression in the cuff tears compared with intact tendons. This increase was least in the massive tears. Apoptosis increases from mild impingement to massive cuff tears (mean 7.3% to 21%)
Although many causes of FAI are described, the vast majority of patients give no history of previous hip disease. The purpose of this study was to investigate the extent to which FAI has an underlying genetic basis, by studying the siblings of patients undergoing surgery for FAI and comparing them with controls.
Participants were classified as:
Normal morphology, no clinical features Abnormal morphology, no clinical features Abnormal morphology, clinical signs but no symptoms Abnormal morphology with symptoms and signs Osteoarthritis.
Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) permits inference of glycosaminoglycan (GAG) distribution. We aimed to determine whether hips with cam deformities have altered GAG content, using dGEMRIC.
2 regions of interest (ROI) were studied:
acetabular cartilage from 12 to 3 O’Clock (T1-Index-acet). total cartilage (femoral and acetabular) for the joint from 9 to 3 O’Clock (T1-Indextotal). The average of all pixels within the given ROI defined the T1-index. For each hip, the ratio of the GAG content T1-Index-acet/T1-Indextotal was calculated. Mean T1-Indexto-tal and T1-Indexacet/T1-Indextotal were compared.
The reproduction of ideal offset is an aim of hip replacement. Determining this measurement from traditional radiology techniques is inaccurate because femoral neck anteversion will foreshorten the femoral neck offset in a standard two dimensional x-ray making the measurement “apparent”. A novel method of determining offset is presented. A computer software program has been developed for pre-operative planning of joint replacements, (Orthopaedic Work Station) The program relies on using a CT scout film for magnification correction and to determine measurement parameters including leg length difference. It was recognised that by collecting extra cross-sectional references that three-dimensional measurement of offset would be possible. The CT scanner has software that allows determination of:
The location of the centre of the femoral head The centroid of the femoral shaft at a point just below the lesser trochanter The centroid of the femoral shaft at a point 150mm below the lesser trochanter For this study the line joining the two centroids is considered the longitudinal axis of the femur. The CT scanner has software that also allows for the centroids to be moved along the longitudinal axis into the plane represented by a perpendicular line from the longitudinal axis to the centre of the femoral head. It is a simple matter to measure the distance between the centroid and the centre of the femoral head to obtain a true offset. A phantom femur was measured using the radiology method described and then measured directly. Exact correlation was established. A study of inter-observer measurement has shown statistically consistent agreement using six observers in twenty cadaver femurs. The method is accurate and uses existing data collected as part of the pre-operative planning process. CT scanning prior to hip replacement, gives less radiation exposure and is more efficient with respect to radiology services than conventional radiology. An intraoperative study may require ethics approval.
The aim of this study was to understand the role tissue hypoxia and apoptosis have on a human model of rotator cuff failure. We studied twenty seven patients with no tear mild impingment (3), no tear moderate impingment (3), no tear severe impingment (3), partial tear (3), small tear (3), moderate tear (3), large tear (3), massive tear (3) and control (3). A supraspinatus tendon biopsy was taken during debridement/repair in all cases (ethics no. C01.071). Control tendon was obtained from the subscapularis tendon of patients undergoing stabilization surgery. Biopsies were analysed using two immunocytological techniques. A monoclonal antibody against BNIP-III (a marker of hypoxia) and TUNEL (Terminal deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling – an apoptotic detection process). An immunoflorescent counterstain DAPI (4′,6-diamidino-2-phenylindol) was used to stain all cells. Positive cells and total cell number were then counted in 10 high powered fields. The results showed a significant increase in BNIP-III expression in the cuff tears compared with intact tendons. This increase was least in the massive tears. Apoptosis increases from mild impingment to massive cuff tears (mean 7.3% to 21%) In conclusion, as tear size increases, the viability of the tendon reduces with increasing hypoxia and apoptosis.
A sibling risk study that shows a statistically significant increase in risk for anteromedial osteoarthritis of the knee. Anteromedial osteoarthritis is a distinct phenotype of osteoarthritis. Previous studies have shown a genetic aetiology to both hip and knee osteoarthritis. The aim of this study was to determine the sibling risk of antero-medial osteoarthritis of the knee. We conducted a retrospective cohort study of 132 probands with primary anteromedial osteoarthritis, who had undergone unicompartmental arthroplasty. Sibling were identified as having symptomatic knee problems by postal Oxford Knee Score (OKS). A positive OKS was defined as an OKS+/− 2SD of the mean of the proband group. Sibling spouses were used as controls. Those siblings &
spouses that were symptomatic from the OKS were invited to undergo Knee X-rays, to look for radiological signs of osteoarthritis. Osteoarthritis was diagnosed as greater than Grade II on the Kell-gren Lawrence classification. The pattern of disease was noted and it was considered if the sibling were suitable for a unicompartmental knee arthroplasty. The prevalence and sibling risk of anteromedial osteoarthritis was determined using a randomly selected single sibling per proband family. The prevalence was determined in the 103 single proband sibling pairs. There was a statistically significant risk within the sibling group P= 0.024 using the Chi square test. The relative risk of anteromedial osteoarthritis was. 3.21(95% CI 1.08 to 9.17) Genetic factors play a major role in the development of anteromedial osteoarthritis.
The aim of this study was to determine cell viability in different stages of rotator cuff tendon tears using a cell viability molecular probe. Surgical biopsies taken from the edge of the Supraspinatus tendon tear from12 patients, 5 women and 7 men, mean age of 61 years were subjected to a cell viability assay using Molecular Probes Live/Dead cell viability assay. Specimens were then incubated with Calcein-AM and Ethidium Homodimer-1 and following snap freezing, sections were viewed under fluorescent microscopy. Cells which remained metabolically active fluoresced green, whereas dead cells were red. Populations of live and dead cells were counted for each specimen on ten high powered (x400 magnification) fields of view. The results show that the percentage of live cells is reduced in large chronic degenerate tears but greatest in acute traumatic tears. In addition, for those cases where tissue was assayed from the edge of the tear and 1 cm more proximally, there was a considerable increase in the percentage of viable cells in more proximal tissue. Use of this simple assay demonstrates high cell viability and consequently good quality tissue in traumatic tears, but lower quality tissue in larger more degenerate tears. This suggests that traumatic lesions have a high propensity to heal while larger more degenerate tears are less likely to heal but have better quality tissue more proximally.
The aim of this study was to observe the macroscopic and microscopic appearance of the Coracoacromial ligament and Subacromial bursa during Subacromial decompression and correlate it with the outcome at 3 months. Twenty patients with Subacromial Impingement without Rotator Cuff tear and five patients with large/massive irreparable Rotator Cuff tears who underwent a Subacromial Decompression. Patients with other shoulder pathology were excluded. Patients completed an Oxford Shoulder Score pre-operatively and their injection history was noted. At operation the shape of the acromion was noted. The macroscopic appearance of the CA ligament and the Subacromial bursa was classified as normal, mild/moderate and severe. Biopsies of the Subacromial bursa and CA ligament were taken and were analysed using histological and contempory immunocytochemical techniques. A histological analysis was performed using Mayer’s Haemotoxylin and Eosin, Toluidine Blue and Congo Red. Sections were stained with primary antibodies against PCNA (Proliferating cell nuclear antigen), Mast Cell Tryptase, CD3 (T-cell), CD20 (B cell), CD 34 (QBEnd 10), CD45 (Leucocyte Common Antigen), CD68 and D2–40 (Lymphatic Endothelial Marker). Post operatively the patients completed an Oxford Shoulder Score at 3 months. All the patients demonstrated an improvement in their Oxford Shoulder Score. The histological analysis demonstrated thickening of the synovial membrane and increased vascularity within the bursa and ligament. Increased numbers of inflammatory cells were present within the ligament and bursa of patients with impingement compared with massive rotator cuff tears. There was a relationship between outcome and the appearance of the bursa and ligament.
Antero-medial osteoarthritis of the knee displays a well recognised pattern of cartilage damage on the medial tibial plateau. Anteriorly there is a full thickness cartilage defect, with transition to a partial thickness defect, becoming full thickness in the posterior third of the plateau. The retained posterior cartilage is macroscopically normal, but no previous study has assessed its histo-logical features. This study characterises the histological changes, to examine if antero-medial OA of the knee represents a model of progressive osteoarthritic cartilage damage. Five unicompartmental resection specimens of patients with idiopathic single compartment antero-medial osteoarthritis were assessed. The samples were stained with H&
E and Saffinin-O stains and reviewed using the Mankin system, an established method for scoring osteoarthritic changes in cartilage (range 0 [normal] to 14 [grossly osteoarthritic]) Digital images of the histology were reviewed by two observers to exclude inter and intra observer error. Each specimen was assessed at 4 interval points (A,B,C,D) along the A-P axis starting from the most posterior aspect of the exposed bone to the area of macroscopically normal cartilage. Three repeat measurements were taken from the macroscopically normal region (D1,D2,D3). The scores were compared to historical age matched controls of non-osteoarthritic cartilage, where a Mankin grade of <
3 suggests normal cartilage. From anterior to posterior the H&
E staining showed a consistent decrease in structural integrity and cellularity of the cartilage, matched by a qualitative decrease in GAG content (Saffinin-O staining). Mean Mankin scores showed a progressive decrease in score; A = 14.0 (95% CI 0), B = 5.8 (95%CI 2.4), C = 4.4 (95%CI 2.5), D = 1.0 (95%CI 0.9) {p=0.04 ANOVA}. Repeated measurements at the macroscopically normal area showed the Mankin grade was maintained; D1= 1.0 (95%CI 0.9), D2 = 0.6 (95%CI 0.5), D3 = 0.6 (95%CI 0.6). The results show that the retained posterior cartilage in antero-medial arthritis has a consistently normal Mankin grade. We suggest the defect represents a model of progressive cartilage damage from near normal (posterior) to the grossly osteoarthritic state (anterior).
Progressive arthritis can occur in association with massive tears of the rotator cuff. Altered joint kinematics are commonly proposed as the principle causative factor but this does not explain the absence of arthropathy in some patients. We have investigated the role of the
The aim of this study was to observe cellular and vascular changes in different stages of full thickness rotator cuff tear. Biopsies of the Supraspinatus tendon in 40 patients with chronic rotator cuff tears undergoing surgery were analysed using histological and contempary immunocytochemical techniques. Sections were stained with primary antibodies against PCNA (Proliferating cell nuclear antigen), CD34 (QBEnd 10), CD45 (Leucocyte Common Antigen), CD68, D2-40 (Lymphatic Endothelial Marker) and Mast Cell Tryptase. A histological analysis was performed with Mayer’s Haemotoxylin and Eosin, Congo Red and Toluidine Blue. The reparative response and inflammatory component (figure 1) of the tissue was seen to diminish as the rotator cuff tear size increased. This was evidenced by increasing degeneration and oedema, reducing fibroblast proliferation, reduced thickening of the synovial membrane and reducing vascularity. Macrophage, other leucocyte and mast cell numbers also reduced as tear size increased. Large and massive tears revealed a higher degree of chondroid metaplasia and amyloid deposition when compared to smaller sized tears. There was no association with the patient’s age or duration of symptoms. Small sized rotator cuff tears retain the greatest potential to heal and have a significant inflammatory component. Tissue from large and massive tears is of such a degenerate nature that it may never heal and this is probably a significant cause of re-rupture after surgical repair in this group. Selection of patients for reconstructive surgery should take into account the composition and healing potential of tendon tissue and its relationship to tear size in chronic tears of the rotator cuff.
The aim of this study was to use motion analysis to study a surgeon’s learning curve for an arthroscopic Bankart repair on a training model in a skills laboratory. Six fellowship trained lower limb surgeons unfamiliar with advanced shoulder arthroscopy performed an arthroscopic Bankart repair on an ALEX shoulder model. Standardised training was given and then an electromagnetic tracking system used to objectively assess hand movements, distance travelled by hands and time taken while the surgeons performed the technique. The arthroscopic repair was repeated three times on four consecutive occasions by each surgeon giving a total of 72 repair episodes. Analysis revealed improvement of all outcome parameters with less hand movements, less distance travelled and less time to complete the task. This study objectively demonstrates a learning curve for arthroscopic Bankart suture in a skills laboratory. It indicates the potential benefits of practicing aspects of arthroscopic techniques in a skills centre on appropriately selected models.
A prospective study was carried out to determine if recognised histological features seen at surgery could help predict those rotator cuff tendon repairs which re-ruptured. 40 rotator cuff tendon edge specimens from 40 patients’ shoulders were analysed histologically following routine mini-open rotator cuff repair. 32/40 underwent Ultrasonography, at a mean time of 35 months post-operatively, to determine repair integrity. The histological features seen at surgery were then compared to the repair integrity of the tendon from which it had been taken. Rotator cuff repairs that remained intact demonstrated a greater reparative response, in terms of increased fibrobast cellularity, cell proliferation and a thickened synovial membrane, than those repairs which reruptured. Larger tears which remained intact showed a higher degree of vasacularity and a significant inflammatory component than those that re-ruptured. Good tissue quality at the time of surgery allows the repair the best chance of remaining intact despite the size of the lesion. Routine histological analysis of the tissue biopsy, preformed in the post-operatively, can now aid the clinician in terms of early management and repair prognosis.
Cuff Tear Arthropathy is characterised by massive rotator cuff tears, glenohumeral joint destruction and joint effusions containing basic calcium phosphate and calcium pyrophosphate dihydrate crystals. We have investigated the role of the ANKH gene in patients with cuff tear arthropathy and the effect of mutations on protein function. The transmembrane protein ANKH transports inorganic pyrophosphate (PPi) from the intracellular to extracellular space. Control of the extracellular levels of PPi is crucial in preventing calcium crystal formation. Genomic DNA was prepared from peripheral blood leucocytes from 22 patients with cuff tear arthropathy diagnosed clinically and radiologically. All 12 exons and exon-intron boundaries from the ANKH gene were PCR amplified and sequenced with BigDye version 3.1 terminator kit (ABI), and analysed using ABI PRISM ® 3100 Genetic Analyser. ANKH complementary DNA (cDNA) was ligated with mammalian expression vector pcDNA3 and site directed mutagenesis was used to make the ANKH mutation detected in the cases. Human articular chondrocytes were transfected with the cDNA variants and PPi concentrations measured. A G-to-A single nucleotide polymorphism in the 3′ untranslated region (3′UTR) of ANKH was identified. The G/A genotype was seen more frequently in the cases (45%) when compared to controls (20%) (p= 0.0008). We observed altered levels of extracellular PPi in human chondrocytes transfected with ANKH cDNA with the 3′ UTR variant when compared with control cells and normal ANKH cDNA. Cuff Tear Arthropathy appears to be heritable via a G-to-A transition in the 3′UTR of ANKH that alters extracellular PPi concentrations in chondrocyte cells. This supports a hypothesis of a primary crystal mediated arthropathy in patients with Cuff Tear Arthropathy.
The aim of the study is to assess the use of patient-based questionnaires in the evaluation of shoulder surgery using a specifically designed database. The patient based questionnaires used in this study were the Oxford Shoulder Score, used to assess shoulder pain and the Oxford Instability Score, used to assess shoulder instability. Two hundred and ninety-five patients were recruited between October 2001 and October 2003. They were prospectively assessed prior to surgery and at regular intervals post operatively. The results demonstrate a high degree of compliance with regard to completion of the questionnaires. Differences in outcome were noted between patients in different diagnostic groups. The specifically designed database allows presentation of outcome information either by individual patient (Figure1) or by procedure group. Patient based questionnaires can be effectively used to audit shoulder practice. A customised database allows rapid and clear presentation of outcome results for both individual patients and groups of patients.
This is the largest reported natural history study of frozen shoulder. 500 patients were identified from a specialist shoulder clinic register with a diagnosis of frozen shoulder based on Codman’s criteria. 273 patients with primary frozen shoulder replied to a detailed postal questionnaire regarding their condition. Mean follow up from symptom onset was 52 months (range 12–240months), with 89% of shoulders followed up for a minimum of 3 years. A positive family history was identified in 20% (n=45) of 1st degree relatives. The relative risk to siblings compared with a control population was 4:1. Patients with mild to moderate symptoms recovered more quickly than those with severe or unbearable symptoms. The mean age of onset was 53 years (range27–85yrs). The female to male ratio was 1.6:1. The condition was bilateral in 20%, with no incidence of ipsilateral recurrence. 22% of patients reported a history of minor trauma to the upper limb prior to the onset of symptoms. 16% were diabetic and 4% reported a history of Dupuytren’s contracture. Right and left arms were affected equally with no relationship to hand dominance. 61% reported slow, and 39% reported sudden onset of symptoms. Generally pain and stiffness improved with time but at 3 and 4 years after onset 13% and 9% respectively still had symptoms. Frozen shoulder affects people mainly in their 6th decade. Genetic factors play an important role in the aetiology. The natural history is for improvement with time, with the less severe symptoms at onset improving most quickly. 9% of patients were still symptomatic at 4 year follow up.
The purpose of this study was to investigate the role that genetics play in the aetiology and symptomatology of full thickness tears of the rotator cuff. From a retrospective, cohort study of 205 patients diagnosed with full thickness rotator cuff tears, we determined, using ultrasound, the prevalence of full thickness tears in their 129 siblings. Using 150 spouses as controls, the relative risk of full thickness rotator cuff tear in siblings v controls was 2.42 (p<
0.0001, 95 % CI 1.77 to 3.31). The relative risk of symptomatic full thickness rotator cuff tear in siblings v controls was 4.65 (p<
0.0001, 95 % CI 2.42 to 8.63). The significantly increased risk for tears in siblings implies that genetic factors play a major role in the development of full thickness tears of the rotator cuff.
The needle was inserted into the supraspinatus tendon of patients with massive, large, medium and small full thickness rotator cuff tears and patients with partial thickness and no tears. Patients undergoing open stabilisation were used as controls. Measurements were made at a number of quantifiable points from the tendon edge to allow the creation of a topographical map of tissue metabolism. Oxygen consumption was calculated using measured oxygen and nitrous oxide levels at each point.
Patients with impingement syndrome but no evidence of a rotator cuff tear also showed a decreased level of oxygen consumption in the anterior part of supraspinatus, but this was significantly higher than the levels seen in the torn tendon. The control group showed no significant alteration in oxygen levels
A systematic review of the English language literature has suggested that the performance of linked and unlinked elbow replacement implants differ in terms of function, survival and mode of failure; however, in this review, only one comparative series using contemporary implants was identified. We have performed a cohort study of Kudo, Souter-Strathclyde and Coonrad-Morrey elbow replacements performed at a single centre by or under the direct supervision of a single Consultant shoulder and elbow surgeon to see if these findings were reflected in clinical practice. The first forty implantations in patients with Rheumatoid arthritis for each device have been reviewed with respect to surgical complications, elbow function and implant survival. The follow-up was shorter for the Coonrad-Morrey cohort. In terms of pain relief and range of motion, the performance of the implants was comparable. The mode of failure was different, with no dislocations/ instability seen with the linked Coonrad-Morrey implants. The loosening rate of the Coonrad-Morrey implants (both clinical and radiographic) was lower, albeit with a shorter follow-up period. The loosening rates seen in this series were higher than those previously reported in the English language literature. We conclude that the functional performance of the implants, at similar stages of the surgical learning curves, are similar in patients with Rheumatoid arthritis, but that use of a linked implant removes the risk of post-operative instability and may reduce the risk of the radiographic and clinical loosening.
The purpose of this study was to investigate the association of endocrine disease with calcific tendinitis and the effects that such disease has on its natural history. A retrospective observational cohort study of 102 consecutive patients (125 shoulders) with calcific tendinitis is presented. Seventy-three (71.6 %) female, 29 (28.4 %) male. Compared with population prevalences, significant levels of endocrine disorders were found in our study cohort. Sixty-six patients (81 shoulders, 62 female (93.9 %), 4 male (6.1 %), mean age 50.3 years) with associated endocrine disease were compared with 36 patients (44 shoulders, 11 female (30.6 %), 25 male (69.4 %), mean age 52.4 years) without endocrine disease. The endocrine cohort were significantly younger than the non-endocrine cohort when symptoms started (mean 40.9 years and 46.9 years respectively, p=0.0026), had significantly longer natural histories (mean 79.7 months compared with 47.1 months, p=0.0015) and a significantly higher proportion underwent operative treatment (46.9 % compared with 22.7 %, p=0.0014). Disorders of thyroid and oestrogen metabolism may contribute to calcific tendinitis aetiology. Classifying calcific tendinitis into Type I idiopathic and Type II secondary or endocrine-related aids prognosis and management.
Between 1972 and 2002 74 patients were treated under the combined care of the orthopaedic oncology service and lymphoma clinic with primary bone lymphoma. We reviewed the seventeen cases affecting the upper limb (23%). Of the seventeen patients nine remain alive. Assessment of the patient’s clinical presentation, histopathological definition, treatment and function outcome was made. The nine survivors were assessed clinically and with the Oxford shoulder score and the Toronto extremity salvage score. Average time from first presentation to diagnosis was 7 months. All seventeen were diagnosed as a B –cell non-Hodgkin’s lymphoma, fifteen cases were high grade and two cases were low grade. The scapula was involved in six, humerus eight and clavicle three cases. Seven patients sustained pathological fractures three of which were at presentation; of these two were treated surgically. Eight patients have subsequently died of their disease. Functional outcome in surviving patients after medical treatment was very good with average TESS score of 79% (52%–99%) and OSS of 27 (12–52). The presentation of lymphoma of the shoulder girdle may mimic benign shoulder conditions and lead to a delay in radiological and histopathological diagnosis. Pathological fracture is a common presentation and complication of treatment, however these fractures have a high chance of healing with medical treatment alone. Although shoulder stiffness remains a problem following medical treatment, overall upper limb function is good. There is little evidence that these patients require surgery in the short to medium term.
From 1985 to 1998 we used the Souter implant for elbow replacement in the rheumatoid population. We have followed this cohort prospectively, and present simple outcome measures including initial pain relief, early complication rates, radiological changes with time, and survivorship. We performed 71 Souter elbow replacements in 62 rheumatoid patients (51 female, 11 male). The average age at surgery was 61 (range 38–79). All patients had end stage arthropathy. Early results and complications were assessed in all patients. Subsequently, ten cases were revised for loosening, and eight patients (10 elbows) died before recent follow up, leaving 51 cases for long term study. Clinical and radiological data were obtained. On early follow up, 94% had no or minimal pain. Thirty-one percent suffered a complication. Overall, 18% cases had ulnar nerve problems and 7% dislocated in the first year. Seven percent had wound problems, including two deep infections. At mean long term follow up of 6 years (range: 2–15 years) there were high rates of satisfaction in patients with retained prostheses. Progressive radiolucency around the humeral component was common and treated expectantly. Late instability was not seen. Pain relief was maintained. There have been few long-term reports on the Souter elbow replacement. This group of patients from a single centre has been followed prospectively. Infection and ulnar nerve complications are comparable with other series, and are less related to prosthesis. The rate of humeral component loosening in this series is high. The rate of dislocation, however, is low. This prosthesis sacrifices stability to transmit forces through the soft tissues. Although stability is acceptable there is no beneficial reduction in loosening.
The purpose of this study was to evaluate the outcomes of treatment of rheumatoid elbows with Kudo Total Elbow Replacements. Between 1993–1997 we performed 39 Kudo Total Elbow Replacements in 35 patients with Rheumatoid Arthritis, aged 39–81 years old (mean age: 60,7 yrs). Eleven patients (13 elbows) were male and 24 (26 elbows) were female. Twenty-eight (28) replacements were performed on the right side and eleven (11) on the left. All the patients were evaluated clinically (pre-op and post-op, using Mayo score system) and radiographically. In seven elbows another procedure (radial head excision (three), radial head excision &
synovectomy (three), arthroscopy &
interposition arthroplasty(one)) had been performed previously for the rheumatoid arthritis. Eight elbows seemed to have ulnar nerve problems pre-op. We followed-up 31 patients (35 elbows). Mean follow-up was 5years (range: 4–8 years). The pre-operative pain had been reduced significantly in almost all patients. In the majority, the movement had also been improved post-operatively. Two elbows were unstable (one subluxated, one dislocated). Both presented early postoperatively. Only one patient developed a postoperative ulnar nerve problem and that resolved. One elbow had a delay in wound healing. Radiolucency appeared around both the humeral and ulnar components in five elbows, around humeral component in two and around ulnar component also in two. Five elbow replacements were revised. Four of them due to aseptic loosening and one due to instability problem (dislocation). No deep infection was noticed in any elbow. In our hands, Kudo Elbow Replacements seemed to have aseptic loosening rates comparable to other series and low dislocation rates.
We carried out a prospective study of 93 patients undergoing surgery for conditions of the rotator cuff during 1994 and 1995. They were assessed before operation and after six months, and four years, using the patient-based Oxford Shoulder Score (OSS), the SF-36 questionnaire and the Constant shoulder score. The response rates were higher for the OSS and SF-36. The correlation coefficients were high (r >
0.5) between all scores at each stage of the study. While all scores improved substantially at six months, the Constant score was reduced significantly at four years. This did not correlate with the patients’ judgement of the change in symptoms or of the success of the operation. Our study suggests that patient-based measures of pain and function can reliably assess outcomes in the medium term after surgery to the shoulder.