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Objectives: To investigate the effect of age-related rotator cuff tears on shoulder strength in a general population cohort., Design: Cross sectional observational study., Setting: This study was set in an outpatient clinic setting in Chingford, North East London, and was a component of the 20 year visit of the Chingford 1000 women cohort., Participants: Individuals were part of the Chingford 1000 women cohort, a 20-year-old longitudinal population study. This cohort has been extensively characterised as representative of the population of the UK. At the 20 year visit, 446 attended for shoulder assessment and were aged between 64 and 87., Primary and Secondary Outcome Measures: Isometric shoulder abduction strength measured using a Nottingham Mecmesin Myometer and the presence of rotator cuff pathology, determined via ultrasound examination (GE voluson i portable ultrasound machine with a 10-16MHz linear probe). Shoulders were classified into normal, abnormal tendon/partial tear, full-thickness tears (>0 and ≤2.5 cm) and full-thickness tears (>2.5 cm). Symptoms were defined using the Oxford Shoulder Score, where an abnormal score was defined as symptomatic., Results: 446 women (891 shoulders) aged 71 (range 65-84) were included in the study. Age, the presence of pain and the non-dominant arm were demonstrated to reduce strength. Rotator cuff tears and pathology had no isolated effect on shoulder strength in those aged under 70. However, in the over 70s full-thickness tears>0 and ≤2.5 cm, and >2.5 cm had mean reductions of 6.3 and 12.7 N, respectively (p<0.001)., Conclusion: Rotator cuff tears of all sizes in those aged under 70 were not associated with a loss of shoulder strength. In those aged over 70, strength was reduced by 30% with small and 40% with large full thickness tears. Loss in strength was associated a loss of ability to perform activities of daily living but only for large tears., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To define the population prevalence of rotator cuff tears and test their association with pain and function loss; determine if severity symptom correlates with tear stage severity, and quantify the impact of symptomatic rotator cuff tears on primary healthcare services in a general population cohort of women., Design: Cross-sectional observational study., Participants: Individuals were part of the Chingford 1000 Women cohort, a 20-year-old longitudinal population study comprising 1003 women aged between 64 and 87, and representative of the population of the UK., Main Outcome Measures: Rotator cuff pathology prevalence on ultrasound, shoulder symptoms using the Oxford Shoulder Score and resultant number of general practitioner (GP) consultations., Results: The population prevalence of full-thickness tears was 22.2%, which increased with age (p=0.004) and whether it was the dominant arm (Relative Risk 1.64, OR 1.58, 95% CI 1.07 to 2.33, p=0.021).Although 48.4% of full-thickness tears were asymptomatic, there was an association between rotator cuff tears and patient-reported symptoms. Individuals with at least one full-thickness tear were 1.97 times more likely than those with bilateral normal tendons (OR 3.53, 95% CI 2.00 to 5.61, p<0.001) to have symptoms. Severity of symptoms was not related to the severity of the pathology until tears are >2.5 cm (p=0.009).In the cohort, 8.9% had seen their GP with shoulder pain and a full-thickness rotator cuff tear, 18.8% with shoulder pain and an abnormality and 29.3% with shoulder pain., Conclusion: Rotator cuff tears are common, and primary care services are heavily impacted. As 50% of tears remain asymptomatic, future research may investigate the cause of pain and whether different treatment modalities, aside from addressing the pathology, need further investigation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To appraise studies reporting on clinical effectiveness and safety of surgical meshes used to augment rotator cuff repairs (RCRs)., Design: Systematic review and meta-analysis., Data Sources: MEDLINE, Embase and Cochrane databases were searched between April 2006 and April 2020., Eligibility Criteria: All studies evaluating adults (≥18 years) undergoing RCR were considered. There were no language restrictions., Data Extraction and Synthesis: Screening, data extraction and quality appraisal were conducted by two independent reviewers. Meta-analysis was conducted using a random-effects models if ≥2 comparative studies reported the same outcome measure. Risk of bias assessment was undertaken for randomised (RoB2, Cochrane) and comparative studies (ROBINS-I, Cochrane)., Results: We included 60 studies, consisting of 7 randomised controlled trials, 13 observational comparative studies and 40 observational case series. All comparative studies reported on shoulder-specific functional outcome scores, 18 on the radiographic occurrence of re-tear and 14 on pain score metrics. All studies contained some risk of bias.Compared with non-augmented repair, a small improvement in shoulder-specific function or pain scores was observed for synthetic patches with a mean improvement of 6.7 points on the University of California Los Angles (UCLA) shoulder score (95% CI 0.1 to 13.4) and 0.46 point reduction on the Visual Analogue Scale (95% CI -0.74 to -0.17), respectively. A reduced likelihood of radiologically observed re-tear was observed for synthetic (risk ratio (RR) 0.41, 95% CI 0.27 to 0.61) and allograft (RR 0.34, 95% CI 0.18 to 0.65) patches. A total of 49 studies reported on the occurrence of complications. Slightly higher crude complication rates were observed following patch-augmented repair (2.1%) than standard repair (1.6%)., Conclusions: While several studies suggest a decreased failure rate and small improvements in shoulder function and pain following augmented RCR, a paucity of rigorous clinical evaluation, for both effectiveness and safety, prevents firm recommendations., Prospero Registration Number: CRD42017057908., Competing Interests: Competing interests: AC has applied for a patent for a device which would be eligible for this type of review if it is approved for clinical use, AR has received educational and research grants from DePuy Ltd., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and purpose - Biological patches can be used to augment rotator cuff tendon repair in an attempt to improve healing and reduce rates of re-rupture. However, little is known about the in vivo tissue response to these patches. We assessed native rotator cuff tissue response after surgical repair and augmentation with 2 commercially available extracellular matrix (ECM) patches. Patients and methods - Patients underwent a rotator cuff repair augmented with either GraftJacket (Wright Medical), Permacol (Zimmer Biomet), or no patch (Control), applied using an onlay technique. A sample of supraspinatus tendon was collected intraoperatively and 4 weeks post-surgery, using ultrasound-guided biopsy. Histology and immunohistochemistry were performed on all samples. Results - The Permacol group (n = 3) and GraftJacket group (n = 4) demonstrated some changes in native tendon ECM compared with the control group (n = 3). Significant disruption of the extracellular matrix of the repaired native supraspinatus, underlying both patches, was observed. The patches did not generally increase cellularity, foreign body giant cell count, or vascularity compared to the control group. 1 patient in the Permacol group had an adverse tissue immune response characterized by extensive infiltration of IRF5 + , CD68 + , and CD206 + cells, suggesting involvement of macrophages with a pro-inflammatory phenotype. No significant differences in protein expression of CD4, CD45, CD68, CD206, BMP7, IRF5, TGFß, and PDPN were observed among the groups. Interpretation - Histological and immunohistochemical analysis of native tendon tissue after patch augmentation in rotator cuff repair raises some concerns about a lack of benefit and potential for harm from these materials.

Background: Rotator cuff tendon repair in humans is a commonly performed procedure aimed at restoring the tendon-bone interface. Despite significant innovation of surgical techniques and suture anchor implants, only 60% of repairs heal successfully. One strategy to enhance repair is the use of bioactive sutures that provide the native tendon with biophysical cues for healing. We investigated the tissue response to a multifilament electrospun polydioxanone (PDO) suture in a sheep tendon injury model characterised by a natural history of failure of healing., Methodology and Results: Eight skeletally mature English Mule sheep underwent repair with electrospun sutures. Monofilament sutures were used as a control. Three months after surgery, all tendon repairs healed, without systemic features of inflammation, signs of tumour or infection at necropsy. A mild local inflammatory reaction was seen. On histology the electrospun sutures were densely infiltrated with predominantly tendon fibroblast-like cells. In comparison, no cellular infiltration was observed in the control suture. Neovascularisation was observed within the electrospun suture, whilst none was seen in the control. Foreign body giant cells were rarely seen with either sutures., Conclusion: This study demonstrates that a tissue response can be induced in tendon with a multifilament electrospun suture with no safety concerns., Competing Interests: I declare that I am the inventor on a patent application related to the technology underlying the manufacturing of the ES suture (WO2015040399, Electrospun filaments, filed in September 2013). This does not alter our adherence to PLOS ONE policies on sharing data and materials. I also confirm on behalf of all authors that there is no other competing interests.

Objectives: The Getting it Right: Addressing Shoulder Pain (GRASP) trial is a large-scale, multicentre, 2×2 factorial randomised controlled trial investigating clinical and cost-effectiveness of a progressive exercise programme versus best-practice advice, with or without corticosteroid injection, for treating people with rotator cuff disorders. Here we describe the development, implementation and details of the physiotherapy-led interventions., Methods: Medical Research Council guidance for developing complex interventions were used, taking into account clinical guidelines, expert and patient opinion, research evidence, current practice variation, and deliverability. A stakeholder meeting of 26 experts, clinicians, researchers, and patient representatives was used to design key components of the interventions. Stakeholders prioritised strengthening posterior rotator cuff muscles and using practical, easy-to-do exercises. The interventions were designed to be deliverable across the UK National Health Service., Results: Progressive exercise consists of up to six sessions with a physiotherapist over 16 weeks. The best-practice advice consists of one face-to-face session with a physiotherapist with substantially greater reliance on self-management. Both interventions include self-management advice, home-exercise instruction, and behaviour-change strategies to target exercise adherence. All participants receive a Participant Information Booklet. The best-practice advice intervention is a self-guided system of progressively challenging exercises, with demonstration videos and written materials. The progressive exercise intervention has a wider range of exercise options, and greater flexibility for tailoring, progression, supervised practice and feedback., Conclusion: GRASP has recruited 708 participants and will provide high quality evidence to inform management of people with shoulder pain due to a rotator cuff disorder. Results are anticipated in 2020., Trial Registration Number: ISRCTN16539266; EudraCT number:2016-002991-28., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and purpose - There is a need to understand the reasons why a high proportion of rotator cuff repairs fail to heal. Using data from a large randomized clinical trial, we evaluated age and tear size as risk factors for failure of rotator cuff repair. Patients and methods - Between 2007 and 2014, 65 surgeons from 47 hospitals in the National Health Service (NHS) recruited 447 patients with atraumatic rotator cuff tendon tears to the United Kingdom Rotator Cuff Trial (UKUFF) and 256 underwent rotator cuff repair. Cuff integrity was assessed by imaging in 217 patients, at 12 months post-operation. Logistic regression analysis was used to determine the influence of age and intra-operative tear size on healing. Hand dominance, sex, and previous steroid injections were controlled for. Results - The overall healing rate was 122/217 (56%) at 12 months. Healing rate decreased with increasing tear size (small tears 66%, medium tears 68%, large tears 47%, and massive tears 27% healed). The mean age of patients with a healed repair was 61 years compared with 64 years for those with a non-healed repair. Mean age increased with larger tear sizes (small tears 59 years, medium tears 62 years, large tears 64 years, and massive tears 66 years). Increasing age was an independent factor that negatively influenced healing, even after controlling for tear size. Only massive tears were an independent predictor of non-healing, after controlling for age. Interpretation - Although increasing age and larger tear size are both risks for failure of rotator cuff repair healing, age is the dominant risk factor.

Background: Progressive cellular and extracellular matrix (ECM) changes related to age and disease severity have been demonstrated in rotator cuff tendon tears. Larger rotator cuff tears demonstrate structural abnormalities that potentially adversely influence healing potential. This study aimed to gain greater insight into the relationship of pathologic changes to tear size by analyzing gene expression profiles from normal rotator cuff tendons, small rotator cuff tears, and large rotator cuff tears., Methods: We analyzed gene expression profiles of 28 human rotator cuff tendons using microarrays representing the entire genome; 11 large and 5 small torn rotator cuff tendon specimens were obtained intraoperatively from tear edges, which we compared with 12 age-matched normal controls. We performed real-time polymerase chain reaction and immunohistochemistry for validation., Results: Torn rotator cuff tendons demonstrated upregulation of a number of key genes, such as matrix metalloproteinase 3, 10, 12, 13, 15, 21, and 25; a disintegrin and metalloproteinase (ADAM) 12, 15, and 22; and aggrecan. Amyloid was downregulated in all tears. Small tears displayed upregulation of bone morphogenetic protein 5. Chemokines and cytokines that may play a role in chemotaxis were altered; interleukins 3, 10, 13, and 15 were upregulated in tears, whereas interleukins 1, 8, 11, 18, and 27 were downregulated., Conclusions: The gene expression profiles of normal controls and small and large rotator cuff tear groups differ significantly. Extracellular matrix remodeling genes were found to contribute to rotator cuff tear pathogenesis. Rotator cuff tears displayed upregulation of a number of matrix metalloproteinase (3, 10, 12, 13, 15, 21, and 25), a disintegrin and metalloproteinase (ADAM 12, 15, and 22) genes, and downregulation of some interleukins (1, 8, and 27), which play important roles in chemotaxis. These gene products may potentially have a role as biomarkers of failure of healing or therapeutic targets to improve tendon healing., (Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: Diseased tendons are characterised by fibrotic scar tissue, which adversely affects tendon structure and function and increases the likelihood of re-injury. The mechanisms and expression profiles of fibrosis in diseased tendon is understudied compared to pulmonary and renal tissues, where transforming growth factor (TGF)β and its associated superfamily are known to be key drivers of fibrosis and modulate extracellular matrix homeostasis. We hypothesised that differential expression of TGFβ superfamily members would exist between samples of human rotator cuff tendons with established disease compared to healthy control tendons., Methods: Healthy and diseased rotator cuff tendons were collected from patients presenting to an orthopaedic referral centre. Diseased tendinopathic (intact) and healthy rotator cuff tendons were collected via ultrasound-guided biopsy and torn tendons were collected during routine surgical debridement. Immunohistochemistry and quantitative real-time polymerase chain reaction were used to investigate the protein and gene expression profiles of TGFβ superfamily members in these healthy and diseased tendons., Results: TGFβ superfamily members were dysregulated in diseased compared to healthy tendons. Specifically, TGFβ-1, TGFβ receptor (R)1 and TGFβ R2 proteins were reduced (p < 0.01) in diseased compared to healthy tendons. At the mRNA level, TGFβ R1 was significantly reduced in samples of diseased tendons, whereas TGFβ R2 was increased (p < 0.01). BMP-2, BMP-7 and CTGF mRNA remained unchanged with tendon disease., Conclusions: We propose that downregulation of TGFβ pathways in established tendon disease may be a protective response to limit disease-associated fibrosis. The disruption of the TGFβ axis with disease suggests associated downstream pathways may be important for maintaining healthy tendon homeostasis. The findings from our study suggest that patients with established tendon disease would be unlikely to benefit from therapeutic TGFβ blockade, which has been investigated as a treatment strategy in several animal models. Future studies should investigate the expression profile of fibrotic mediators in earlier stages of tendon disease to improve understanding of the targetable mechanisms underpinning tendon fibrosis.

There is increasing evidence for a progressive extracellular matrix change in rotator cuff disease progression. Directly surrounding the cell is the pericellular matrix, where assembly of matrix aggregates typically occurs making it critical in the response of tendon cells to pathological conditions. Studies in animal models have identified type VI collagen, fibrillin-1 and elastin to be located in the pericellular matrix of tendon and contribute in maintaining the structural and biomechanical integrity of tendon. However, there have been no reports on the localization of these proteins in human tendon biopsies. This study aimed to characterize the distribution of these ECM components in human rotator cuffs and gain greater insight into the relationship of pathology to tear size by analyzing the distribution and expression profiles of these ECM components. Confocal microscopy confirmed the localization of these structural molecules in the pericellular matrix of the human rotator cuff. Tendon degeneration led to an increased visibility of these components with a significant disorganization in the distribution of type VI collagen. At the genetic level, an increase in tear size was linked to an increased transcription of type VI collagen and fibrillin-1 with no significant alteration in the elastin levels. This is the first study to confirm the localization of type VI collagen, elastin and fibrillin-1 in the pericellular region of human supraspinatus tendon and assesses the effect of tendon degeneration on these structures, thus providing a useful insight into the composition of human rotator cuff tears which can be instrumental in predicting disease prognosis.

Background: Pain related to rotator cuff tendinopathy is a common problem, but little is known regarding the origin and cause of pain from the tendon substance. No study to date has looked at the association between tissue changes and patient outcomes., Purpose: To describe the peripheral neuronal phenotype in painful rotator cuff tears and to determine correlations between tissue changes and clinical outcome measures., Study Design: Controlled laboratory study., Methods: Tissue samples of the supraspinatus were taken from patients undergoing surgery to repair a rotator cuff tendon tear. Patients were classified as having small/medium or large/massive tears. Control tissue was obtained from patients undergoing surgery for posttraumatic shoulder instability. Immunohistochemical techniques were performed using antibodies to known nociceptive and neuronal markers as well as general tissue structural markers., Results: There was no correlation between tissue changes and patient-reported outcomes. A significant increase in the expression of glutamate was seen in tendon tears. There were differences in the expression of metabotropic and ionotropic glutamate receptors. Expression changes were also observed for markers of the sensory and autonomic systems; however, no differences were found in neurotrophins., Conclusion: Glutamate and the glutaminergic system play a key role in painful human tendon tears; however, the exact role is still uncertain, as glutamate is highly involved in both pain and metabolic pathways., Clinical Relevance: This study has identified a number of markers that could be potential therapeutic targets., (© 2014 The Author(s).)

Background: Augmentation of rotator cuff tears aims to strengthen the repair and reduce rerupture, yet studies still report high failure rates. This study determines key mechanical properties of rotator cuff repair patches, including establishing values for toughness and measuring the shear properties of repair patches and human rotator cuff tendons. We hypothesized that different repair grafts would (1) have varying material parameters, and (2) not all have mechanical properties similar to human rotator cuff tendons., Materials and Methods: Eight specimens each from the Restore, GraftJacket, Zimmer Collagen Repair, and SportsMesh repair patches were tested to failure in tension and for suture pullout. We assessed ultimate tensile strength, tensile (Young's) modulus, and failure strain. This study also established toughness values and shear data. Storage modulus was calculated using dynamic shear analysis for the patches and 18 samples of normal rotator cuff tendon., Results: We report significant variability in important mechanical properties of repair patches, with the mechanical parameters of the patches diverting variously-and often significantly-from values for human rotator cuff tendon., Conclusions: The repair grafts tested all displayed significant variation in their mechanical properties and had at least some reduced parameters compared with human rotator cuff tendons. This study offers experimentally derived information of value to surgeons when selecting rotator cuff repair grafts. A better understanding of the mechanical suitability of repair grafts for supporting human rotator cuffs is needed if repair patches are to provide a solution for the clinical problem of failure of rotator cuff repairs., (Copyright © 2012 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.)

Persistently high failure rates that are reported after rotator cuff repairs have encouraged greater understanding of the pathophysiology that underlies rotator cuff tears. Biologic changes that contribute to the pathogenesis of rotator cuff tears and tendinopathies, as well as adaptation after these changes, have been well described. A subset of patients with a genetic predisposition to early onset of rotator cuff tears and earlier symptom and disease progression have been identified. Many biologic changes occurring at the gene level have been identified. Pathways that are believed to contribute to rotator cuff tendinopathies include extracellular matrix remodeling, angiogenesis, changes in metabolism, apoptosis, and stress-related genes. Metaplasia of rotator cuff cells is contributed to by changes in gene expression. Modification of these gene changes may be possible through mechanical loading, drugs, or cellular manipulation. Gene changes may offer greater insight into why certain tears fail to heal and help to identify therapeutic targets., (Copyright © 2012 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.)

The cause of the high failure rates often observed 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. 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 differential scanning calorimetry. Thermal properties were measured for 28 human biopsies taken intra-operatively from normal, small, and massive rotator cuff tendon tears in this powered study. Denaturation temperatures are represented by T(onset) (°C) and T(peak) (°C). The T(onset) is proposed to represent water-amide hydrogen bond breakage and resulting protein backbone mobility. T(peak) reportedly corresponds to the temperature at which the majority of proteins fall out of solution. Denaturation enthalpy (ΔH) should correlate with the amount of triple helical structure that is denatured. Fluorescence and confocal microscopy allowed quantitative validation. Small and massive rotator cuff tears had significantly higher T(onset), T(peak), and ΔH compared to controls. Polarized light microscopy of torn tendons confirmed greater collagen structural disruption compared to controls. These novel findings suggest greater quantifiable collagen structural disruption in rotator cuff tears, compared to controls. This study offers insight into possible mechanisms for the reduced strength of torn tendons and may explain why repaired tendons fail to heal., (Copyright © 2011 Orthopaedic Research Society.)

We investigated the role of two genes, ANKH and TNAP, in patients with cuff tear arthropathy. These genes encode proteins which regulate the extracellular concentration of inorganic pyrophosphate, fluctuations of which can lead to calcium crystal formation. Variants were detected by direct sequencing of DNA and their frequencies compared with healthy controls. The effect of variants on protein function was further studied by in vitro approaches. Variant genotypes were observed more frequently in the cases when compared with controls in ANKH (45% and 20%) and TNAP (32% and 9%). Variants in ANKH altered inorganic pyrophosphate (PPi) concentrations in transfected human chondrocytes. There was a higher mean serum concentration of TNAP detected in female patients compared with normal ranges. Cuff tear arthropathy is associated with variants in ANKH and TNAP that alter extracellular inorganic pyrophosphate concentrations causing calcium crystal deposition. This supports a theory that genetic variants predispose patients to primary crystal deposition which when combined with a massive rotator cuff tear leads to the development of arthritis.

Background and purpose -- The number of shoulder registries increases. We assessed international trends in use of shoulder arthroplasty, and described the current state of procedure selection and outcome presentation as documented in national and regional joint registries. Methods -- Published reports from 9 population-based shoulder arthroplasty registries (country/region: Norway, Sweden, New Zealand, Denmark, California, Australia, Emilia-Romagna, Germany, and United Kingdom) were analyzed. Data were extracted on age, sex, disease indication, type of surgical procedure, surgical volume, and outcomes. Results -- Shoulder arthroplasty incidence rate in 2012 was 20 procedures/105 population with a 6-fold variation between the highest (Germany) and lowest (United Kingdom) country. The annual incidence rate increased 2.8-fold in the past decade. Within the indications osteoarthritis, fracture, and cuff-tear arthropathy variations in procedure choice between registries were large. Outcomes evaluation focused on revision in all registries, but different measures and strata were used. Only Australia provided revision rates for prosthesis brands stratified by both indication and procedure. Finally, in 2 registries with available data surgeons performed on average 10-11 procedures yearly. Interpretation -- Annual incidence rates of shoulder arthroplasty have almost tripled over the past decade. There is wide variation in procedure selection for the major indications, a low average surgeon volume, a substantial number of brands with small annual volume, and large variation in outcome presentation. The internationally increasing registry activity is an excellent basis for improving the so far weak evidence in shoulder arthroplasty. [ABSTRACT FROM AUTHOR]