R J Murphy

Temporal trends and geographical variation in the use of subacromial decompression and rotator cuff repair of the shoulder in England

We explored the trends over time and the geographical variation in the use of subacromial decompression and rotator cuff repair in 152 local health areas (Primary Care Trusts) across England. The diagnostic and procedure codes of patients undergoing certain elective shoulder operations between 2000/2001 and 2009/2010 were extracted from the Hospital Episode Statistics database. They were grouped as 1) subacromial decompression only, 2) subacromial decompression with rotator cuff repair, and 3) rotator cuff repair only. The number of patients undergoing subacromial decompression alone rose by 746.4% from 2523 in 2000/2001 (5.2/100 000 (95% confidence interval (CI) 5.0 to 5.4) to 21 355 in 2009/2010 (40.2/100 000 (95% CI 39.7 to 40.8)). Operations for rotator cuff repair alone peaked in 2008/2009 (4.7/100 000 (95% CI 4.5 to 4.8)) and declined considerably in 2009/2010 (2.6/100 000 (95% CI 2.5 to 2.7)). Given the lack of evidence for the effectiveness of these operations and the significant increase in the number of procedures being performed in England and elsewhere, there is an urgent need for well-designed clinical trials to determine evidence of clinical effectiveness.

Glucocorticoids induce senescence in primary human tenocytes by inhibition of sirtuin 1 and activation of the p53/p21 pathway: in vivo and in vitro evidence

Cellular senescence is an irreversible side effect of some pharmaceuticals which can contribute to tissue degeneration. Objective To determine whether pharmaceutical glucocorticoids induce senescence in tenocytes. Methods Features of senescence (β-galactosidase activity at pH 6 (SA-β-gal) and active mammalian/mechanistic target of rapamycin (mTOR) in cell cycle arrest) as well as the activity of the two main pathways leading to cell senescence were examined in glucocorticoid-treated primary human tenocytes. Evidence of senescence-inducing pathway induction in vivo was obtained using immunohistochemistry on tendon biopsy specimens taken before and 7 weeks after subacromial Depo-Medrone injection. Results Dexamethasone treatment of tenocytes resulted in an increased percentage of SA-βgal-positive cells. Levels of phosphorylated p70S6K did not decrease with glucocorticoid treatment indicating mTOR remained active. Increased levels of acetylated p53 as well as increased RNA levels of its pro-senescence effector p21 were evident in dexamethasone-treated tenocytes. Levels of the p53 deacetylase sirtuin 1 were lower in dexamethasone-treated cells compared with controls. Knockdown of p53 or inhibition of p53 activity prevented dexamethasone-induced senescence. Activation of sirtuin 1 either by exogenous overexpression or by treatment with resveratrol or low glucose prevented dexamethasone-induced senescence. Immunohistochemical analysis of tendon biopsies taken before and after glucocorticoid injection revealed a significant increase in the percentage of p53-positive cells (p=0.03). The percentage of p21-positive cells also tended to be higher post-injection (p=0.06) suggesting glucocorticoids activate the p53/p21 senescence-inducing pathway in vivo as well as in vitro. Conclusion As cell senescence is irreversible in vivo, glucocorticoid-induced senescence may result in long-term degenerative changes in tendon tissue.

Glucocorticoids induce specific ion-channel-mediated toxicity in human rotator cuff tendon: a mechanism underpinning the ultimately deleterious effect of steroid injection in tendinopathy?

Background Glucocorticoid injection (GCI) and surgical rotator cuff repair are two widely used treatments for rotator cuff tendinopathy. Little is known about the way in which medical and surgical treatments affect the human rotator cuff tendon in vivo. We assessed the histological and immunohistochemical effects of these common treatments on the rotator cuff tendon. Study design Controlled laboratory study. Methods Supraspinatus tendon biopsies were taken before and after treatment from 12 patients undergoing GCI and 8 patients undergoing surgical rotator cuff repair. All patients were symptomatic and none of the patients undergoing local GCI had full thickness tears of the rotator cuff. The tendon tissue was then analysed using histological techniques and immunohistochemistry. Results There was a significant increase in nuclei count and vascularity after rotator cuff repair and not after GCI (both p=0.008). Hypoxia inducible factor 1α (HIF-1α) and cell proliferation were only increased after rotator cuff repair (both p=0.03) and not GCI. The ionotropic N-methyl-d-aspartate receptor 1 (NMDAR1) glutamate receptor was only increased after GCI and not rotator cuff repair (p=0.016). An increase in glutamate was seen in both groups following treatment (both p=0.04), while an increase in the receptor metabotropic glutamate receptor 7 (mGluR7) was only seen after rotator cuff repair (p=0.016). Conclusions The increases in cell proliferation, vascularity and HIF-1α after surgical rotator cuff repair appear consistent with a proliferative healing response, and these features are not seen after GCI. The increase in the glutamate receptor NMDAR1 after GCI raises concerns about the potential excitotoxic tendon damage that may result from this common treatment.

An Independent Learning Method for Orthopaedic Surgeons Performing Shoulder Ultrasound to Identify Full-Thickness Tears of the Rotator Cuff

BACKGROUND There is an evolving interest in shoulder ultrasound performed by orthopaedic surgeons as part of routine clinical assessment of the rotator cuff in a so-called one-stop clinic. This study investigated the accuracy of ultrasound assessment of rotator cuff integrity performed by orthopaedic surgeons without prior experience of ultrasound who were following our proposed learning protocol. METHODS We studied four surgeons without previous experience with shoulder ultrasound and monitored their ability to evaluate rotator cuff integrity using ultrasound compared with findings at arthroscopy. The surgeons attended a formal training course and were taught a protocol to identify and size full-thickness tears of the rotator cuff. The surgeons performed preoperative scans on the day that patients underwent shoulder arthroscopy. This allowed the surgeons to receive same-day feedback with comparison of arthroscopic images and ultrasound images. RESULTS One hundred and fifty-nine shoulders were scanned by the surgeons in the study. In the initial training period, surgeons who performed >100 scans demonstrated a sensitivity of 94% and a specificity of 88% (a positive predictive value of 79% and a negative predictive value of 97%) for the identification of a full-thickness tear and agreed with intraoperative sizing of the defect in 84% of the scans. In the later training period, the predictive values showed a sensitivity of 90% and a specificity of 97% (a positive predictive value of 95% and a negative predictive value of 94%) for the identification of a full-thickness tear and agreement with intraoperative sizing for 95% of the scans. CONCLUSIONS The predictive values obtained in this study for the evaluation of rotator cuff integrity were comparable with published results from experienced radiologists. This study demonstrates the capacity of our proposed learning protocol to train surgeons without previous ultrasound experience to reliably evaluate rotator cuff integrity using ultrasound within fifty to 100 scans.

Platelet-Rich Plasma Injection With Arthroscopic Acromioplasty for Chronic Rotator Cuff Tendinopathy A Randomized Controlled Trial

Background: Platelet-rich plasma (PRP) has been proposed to augment tendon healing through improving tissue structure during the initial repair phase. Purpose: To investigate both the clinical and tissue effects of the coapplication of PRP injection with arthroscopic acromioplasty (AA) in patients with chronic rotator cuff tendinopathy. Design: Randomized controlled trial; Level of evidence, 1. Methods: The study comprised 60 randomized patients diagnosed with rotator cuff tendinopathy (55% women) aged between 35 and 75 years. Patients were randomized to AA alone or in combination with an injection of autologous PRP into the subacromial bursa (AA + PRP). Efficacy of treatment was assessed by analysis of patient-reported outcomes up to 2 years after treatment (Oxford Shoulder Score [OSS]) and by analysis of tendon biopsy specimens taken 12 weeks after treatment. Results: There was no significant difference in the OSS between AA alone and AA + PRP at any time point in the study. From 12 weeks onward, there was a significant increase in the OSS for both groups compared with their baseline scores (P < .001). Bonar scoring determined no significant change in tissue structure with the coapplication of PRP compared with surgery alone. The number of blood vessels and tendon cellularity were significantly decreased in tissue biopsy specimens taken from PRP-treated patients. The expression of p53-positive apoptotic cells increased after AA + PRP but decreased after AA alone. Conclusion: Arthroscopic acromioplasty significantly improves long-term clinical outcomes up to 2 years. The coapplication of PRP did not affect clinical outcomes. PRP significantly alters the tissue characteristics in tendons after surgery with reduced cellularity and vascularity and increased levels of apoptosis. Clinical Relevance: The coapplication of PRP did not improve clinical outcomes and may have potential deleterious effects on healing tendons. Registry Number: ISRCTN 10464365

Tendon Tissue Engineering: The Potential Application of Stem Cells, Biological Factors, and Repair Scaffolds to Improve Rotator Cuff Tendon Tears

High failure rates associated with traditional surgical repair of rotator cuff tears have encouraged the search for new methods to improve surgical repair. Assuming that optimal surgical techniques are being employed, then it is possible that surgical repairs may require augmentation either mechanically or biologically. Tissue-engineering approaches are being used increasingly to identify applications which could augment surgical repairs. Various approaches to the problem of tendon healing have been employed. Additional mechanical support is offered by augmentation patches, which are both biological and synthetic. Enhancement of healing is encouraged by the use of stem cells and biological agents. This article reviews all three areas of research, particularly focusing on their application to rotator cuff tendon tears. Though promising, no single treatment currently offers effective and definitive healing outcomes. It may therefore be prudent to modify approaches by combining two or three of these factors. Stem cells could be applied to tendons with concomitant use of biological factors to enhance healing, and delivered by an appropriate scaffold or delivery vehicle.

Differences in glutamate receptors and inflammatory cell numbers are associated with the resolution of pain in human rotator cuff tendinopathy

IntroductionThe relationship between peripheral tissue characteristics and pain symptoms in soft tissue inflammation is poorly understood. The primary aim of this study was to determine immunohistochemical differences in tissue obtained from patients with persistent pain and patients who had become pain-free after surgical treatment for rotator cuff tendinopathy. The secondary aim was to investigate whether there would be differences in glutaminergic and inflammatory gene expression between disease-derived and healthy control cells in vitro.MethodsSupraspinatus tendon biopsies were obtained from nine patients with tendon pain before shoulder surgery and from nine further patients whose pain had resolved completely following shoulder surgery. Histological markers relating to the basic tendon characteristics, inflammation and glutaminergic signalling were quantified by immunohistochemical analysis. Gene expression of glutaminergic and inflammatory markers was determined in tenocyte explants derived from painful rotator cuff tendon tears in a separate cohort of patients and compared to that of explants from healthy control tendons. Dual labelling was performed to identify cell types expressing nociceptive neuromodulators.ResultsTendon samples from patients with persistent pain demonstrated increased levels of metabotropic glutamate receptor 2 (mGluR2), kainate receptor 1 (KA1), protein gene product 9.5 (PGP9.5), CD206 (macrophage marker) and CD45 (pan-leucocyte marker) versus pain-free controls (p <0.05). NMDAR1 co-localised with CD206-positive cells, whereas PGP9.5 and glutamate were predominantly expressed by resident tendon cells. These results were validated by in vitro increases in the expression of mGluR2, N-methyl-D-aspartate receptor (NMDAR1), KA1, CD45, CD206 and tumour necrosis factor alpha (TNF-α) genes (p <0.05) in disease-derived versus control cells.ConclusionsWe conclude that differences in glutamate receptors and inflammatory cell numbers are associated with the resolution of shoulder pain in rotator cuff tendinopathy, and that disease-derived cells exhibit a distinctly different neuro-inflammatory gene expression profile to healthy control cells.

Differential growth on sutures of tendon cells derived from torn human rotator cuff

Rotator cuff tendon pathology is proposed to account for 30-70% of all shoulder pain and surgical repair with a nonabsorbable suture is the common option for painful rotator cuff tears that have failed conservative treatment. A number of studies have suggested the beneficial effect of augmenting the repair with implants constructed from polymers used for sutures. Thus, it was of interest to investigate the affinity of tendon-derived fibroblasts, often thought to be the repairing agents of torn tendons, to commonly used sutures. The aim of this comparative study was to evaluate the suitability of these sutures for the construction of a patch by measuring cell survival, proliferation, and migration of human tendon-derived fibroblasts on different sutures. To ensure relevance to the target tissue, cells used in this study were obtained from torn human supraspinatus tendons. An initial comparison of cell proliferation on suture mats showed an overall positive proliferation on polyester (Ethibond) and polydioxanone (PDSII) mats and a reduction of proliferation on vicryl (polyglactin 910) compared to day one. The results also showed that the degradation products of vicryl had a negative effect on cell growth over 10 weeks. Of the commercial sutures selected and tested, Ethibond showed the best performance in terms of cell attachment and increase in biomass. The degradable PDSII also showed good interaction with cells in vitro, but relatively poor cell adhesion. This study provides useful and clinically relevant information, which could help to guide future considerations for candidate materials from which to construct tissue repair patches.

Effect of tear size, corticosteroids and subacromial decompression surgery on the hierarchical structural properties of torn supraspinatus tendons

Objectives The effects of disease progression and common tendinopathy treatments on the tissue characteristics of human rotator cuff tendons have not previously been evaluated in detail owing to a lack of suitable sampling techniques. This study evaluated the structural characteristics of torn human supraspinatus tendons across the full disease spectrum, and the short-term effects of subacromial corticosteroid injections (SCIs) and subacromial decompression (SAD) surgery on these structural characteristics. Methods Samples were collected inter-operatively from supraspinatus tendons containing small, medium, large and massive full thickness tears (n = 33). Using a novel minimally invasive biopsy technique, paired samples were also collected from supraspinatus tendons containing partial thickness tears either before and seven weeks after subacromial SCI (n = 11), or before and seven weeks after SAD surgery (n = 14). Macroscopically normal subscapularis tendons of older patients (n = 5, mean age = 74.6 years) and supraspinatus tendons of younger patients (n = 16, mean age = 23.3) served as controls. Ultra- and micro-structural characteristics were assessed using atomic force microscopy and polarised light microscopy respectively. Results Significant structural differences existed between torn and control groups. Differences were identifiable early in the disease spectrum, and increased with increasing tear size. Neither SCI nor SAD surgery altered the structural properties of partially torn tendons seven weeks after treatment. Conclusions These findings may suggest the need for early clinical intervention strategies for torn rotator cuff tendons in order to prevent further degeneration of the tissue as tear size increases. Further work is required to establish the long-term abilities of SCI and SAD to prevent, and even reverse, such degeneration. Cite this article: Bone Joint Res 2014;3:252–61.

Management of shoulder pain in general practice

Shoulder pain is a common problem accounting for significant morbidity and disability in the community. As the third most frequent musculoskeletal problem presenting in primary care, shoulder pain has a prevalence of 16–26% in the UK population and around 1% of adults consult their GP with a new presentation of shoulder pain each year. The aetiology of shoulder pain is diverse and many disorders present with similar symptoms and signs. Patients with shoulder pain suffer from a spectrum of functional disability; they may have difficulty performing many essential activities of daily living and are often forced to take time off work.