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Background: A rotator cuff tear is a common disabling shoulder problem. Symptoms include pain, weakness, lack of mobility and sleep disturbance. Many patients require surgery to repair the tear; however, there is a high failure rate. There is a pressing need to improve the outcome of rotator cuff surgery. The use of patch augmentation to provide support to the healing process and improve patient outcomes holds new promise. Different materials (e.g. human/animal skin or intestine tissue, and completely synthetic materials) and processes (e.g. woven or a mesh) have been used to produce patches. However, clinical evidence on their use is limited. The patch augmented rotator cuff surgery (PARCS) feasibility study aimed to determine the design of a definitive randomised controlled trial (RCT) assessing the effectiveness and cost-effectiveness of a patch to augment surgical repair of the rotator cuff that is both acceptable to stakeholders and feasible., Methods: A mixed methods feasibility study of conducing a subsequent RCT. The project involved six stages: a systematic review of clinical evidence; a survey of the British Elbow and Shoulder Society's (BESS) surgical membership; a survey of surgeon trialists; focus groups and interviews with stakeholders; a two-round Delphi study administered via online questionnaires and a 2-day consensus meeting., Results: The BESS surgeons' survey identified a variety of patches in use (105 (21%) responses received). Twenty-four surgeons (77%) completed the trialist survey relating to trial design. Four focus groups were conducted involving 24 stakeholders. Twenty-nine (67% of invited) individuals took part in the Delphi. Differing views were held on a number of aspects including the appropriate patient population for trial participation. Agreement on the key research questions and the outline of two potential RCTs were achieved through the Delphi study and the consensus meeting., Conclusions: Randomised comparisons of on-lay patch use for completed rotator cuff repairs, and bridging patch use for partial rotator cuff repairs were identified as areas for further research. The value of an observational study to assess safety concerns of patch use was also highlighted. The main limitation was that the findings were influenced by the participants, who might not necessarily reflect all stakeholders., (© 2021. The Author(s).)

Background: A rotator cuff tear is a common, disabling shoulder problem. Symptoms may include pain, weakness, lack of shoulder mobility and sleep disturbance. Many patients require surgery to repair the tear; however, there is a high failure rate. There is a need to improve the outcome of rotator cuff surgery, and the use of patch augmentation (on-lay or bridging) to provide support to the healing process and improve patient outcomes holds promise. Patches have been made using different materials (e.g. human/animal skin or tissue and synthetic materials) and processes (e.g. woven or mesh)., Objectives: The aim of the Patch Augmented Rotator Cuff Surgery (PARCS) feasibility study was to determine the design of a definitive randomised controlled trial assessing the clinical effectiveness and cost-effectiveness of a patch to augment surgical repair of the rotator cuff that is both acceptable to stakeholders and feasible., Design: A mixed-methods feasibility study of a randomised controlled trial., Data Sources: MEDLINE, EMBASE and the Cochrane Library databases were searched between April 2006 and August 2018., Methods: The project involved six stages: a systematic review of clinical evidence, a survey of the British Elbow and Shoulder Society's surgical membership, a survey of surgeon triallists, focus groups and interviews with stakeholders, a two-round Delphi study administered via online questionnaires and a 2-day consensus meeting. The various stakeholders (including patients, surgeons and industry representatives) were involved in stages 2-6., Results: The systematic review comprised 52 studies; only 15 were comparative and, of these, 11 were observational (search conducted in August 2018). These studies were typically small (median number of participants 26, range 5-152 participants). There was some evidence to support the use of patches, although most comparative studies were at a serious risk of bias. Little to no published clinical evidence was available for a number of patches in clinical use. The membership survey of British Elbow and Shoulder surgeons [105 (21%) responses received] identified a variety of patches in use. Twenty-four surgeons (77%) completed the triallist survey relating to trial design. Four focus groups were conducted, involving 24 stakeholders. Differing views were held on a number of aspects of trial design, including the appropriate patient population (e.g. patient age) to participate. Agreement on the key research questions and the outline of two potential randomised controlled trials were achieved through the Delphi study [29 (67%)] and the consensus meeting that 22 participants attended., Limitations: The main limitation was that the findings were influenced by the participants, who are not necessarily representative of the views of the relevant stakeholder groups., Conclusion: The need for further clinical studies was clear, particularly given the range and number of different patches available., Future Work: Randomised comparisons of on-lay patch use for completed rotator cuff repairs and bridging patch use for partial rotator cuff repairs were identified as areas for further research. The value of an observational study to assess safety concerns of patch use was also highlighted. These elements are included in the trial designs proposed in this study., Study Registration: The systematic review is registered as PROSPERO CRD42017057908., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 25, No. 13. See the NIHR Journals Library website for further project information.

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: Rotator cuff tears are a common cause of shoulder pain and can result in prolonged periods of pain, disability and absence from work. Rotator cuff repair surgery is increasingly used in an attempt to resolve symptoms but has failure rates of around 40%. There is a pressing need to improve the outcome of rotator cuff repairs. Patch augmentation increasingly being used within the NHS in an attempt to reduce repair failures. The aim of this survey was to determine current UK practice and opinion relating to the factors that influence choice of patch, current patient selection and willingness to assist with generation of improved evidence., Methods: An online survey was sent to the surgeon members of the British Elbow and Shoulder Society (BESS). Questions covered respondent demographics, experience with patches, indications for patch augmentation and willingness to be involved in a randomised trial of patch augmented rotator cuff surgery., Results: The response rate was 105/550 (19%). 58% of respondents had used a patch to augment rotator cuff surgery. 70% of patch users had undertaken an augmented repair within the last 6 months. A wide surgical experience in augmentation was reported (ranging 1 to 200 implants used). However, most surgeons reported low volume usage, with a median of 5 rotator cuff augmentation procedures performed. At least 10 different products had been used. Most of the patches used were constructed from human decellularised dermis tissue, although porcine derived and synthetic based patches had also been used. Only 3-5% stated they would undertake an augmented repair for small tears across ages, whereas 28-40% and 19-59% would do so for large or massive tears respectively. When assessing patient suitability, patient age seemed relevant only for those with large and massive tears. Half of the surgeons reported an interest in taking part in a randomised controlled trial (RCT) evaluating the role of patch augmentation for rotator cuff surgery, with a further 22% of respondent's undecided., Conclusions: A variety of patches have been used by surgeons to augment rotator cuff repair with a wide range of operator experience. There was substantial uncertainty about which patch to use and differing views on which patients were most suitable. There is a clear need for robust clinical evaluation and further research in this area., Competing Interests: Author AC has been developing a patch for potential use to rotator cuff surgery. None of the other authors have any COIs to declare.

A symptomatic bone stress reaction is an early pathological feature, which can lead to stress fractures. It typically affects bones of the lower limbs in response to unaccustomed disproportional compressive loading. Professional sportspeople are susceptible to both bone stress reaction and stress fractures, where training regimes and competition predispose to overuse injuries. We discuss a unique case of a professional cricketer developing pain in the throwing arm due to bone stress reaction in the distal humerus, as confirmed on MRI. Modification of the patient's training regime, presented in this case, facilitated complete recovery within 6 weeks. The positive response to modified training suggests a biomechanical origin of the pain. This case illustrates that tensile stress associated with throwing activities can result in a symptomatic bone stress reaction of the humerus in elite cricketers., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

There is emerging evidence of the impact of infections on rheumatoid arthritis pathogenesis and flares. We aimed to study the association between antibiotic use (and timing of use), and the occurrence of flares in patients with RA. We nested a self-controlled case series (SCCS) of patients who have RA flares within a newly diagnosed RA cohort (n = 31,992) from the UK Clinical Practice Research Datalink (CPRD) GOLD dataset. We determined associations between exposure to antibiotics (beta-lactam, imidazole, macrolide, nitrofurantoin, quinolone, sulphonamide and trimethoprim, and tetracycline) and the occurrence of RA flares. Conditional fixed-effects Poisson regression models were used to determine incidence rate ratios (IRR), offset by the natural logarithm of risk periods. A total of 1,192 (3.7%) of RA subjects had one or more flare/s during the study period, and were therefore included. Use of sulphonamide and trimethoprim was associated with an increased risk of RA flare at 29-90 days (IRR 1.71, CI 1.12-2.59, p = 0.012); 91-183 days (IRR 1.57, CI 1.06-2.33, p = 0.025); and 184-365 days (IRR 1.44, CI 1.03-2.02, p = 0.033) after commencement of antibiotic treatment. No other antibiotic group/s appear associated with RA flare/s risk. Usage of sulphonamide and trimethoprim antibiotics, is associated with a 70% increased risk of RA flare at 1-3 months, which decreases but remains significant up to 12 months after treatment. We hypothesise that the delayed onset of RA flares after specific antibiotics is mediated through the gut or urinary microbiomes. Further epidemiological and mechanistic research is needed to determine the role of infections in RA.

Background: Shoulder pain is a common problem in the general population and is responsible for prolonged periods of disability, loss of productivity, absence from work and inability to carry out household activities. Rotator cuff problems account for up to 70% of shoulder pain problems and are the third most prevalent musculoskeletal disorder after those occurring in the lower back and neck. Rotator cuff surgery has high failure rates (25-50% within 12 months), and as a result, there is a pressing need to improve the outcome of rotator cuff surgery. Patch augmented surgery for rotator cuff repairs has recently been developed and is increasingly being used within the UK National Health Service. Patch augmented surgery could lead to a dramatic improvement in patient and surgical outcomes, but its clinical and cost effectiveness needs rigorous evaluation. The existing evidence on the use of patches may be at risk of bias as currently only a small number of single-centre comparative studies appear to have been carried out. Additionally, it is unclear for which patches a clinical study (comparative and non-comparative) has been conducted. This paper outlines the protocol for a systematic review intended to summarise the best available clinical evidence and will indicate what further research is required., Methods: Electronic databases (Medline, Embase and Cochrane) will be systematically searched between April 2006 and the present day for relevant publications using a specified search strategy, which can be adapted for the use in multiple electronic databases, and inclusion criteria. Screening of both titles and abstracts will be done by two independent reviewers with any discrepancies resolved by a third independent reviewer. Data extraction will include information regarding the type of participants, type of intervention and outcomes including but not limited to shoulder-specific function and pain scores, patch-related adverse events and type of study. The results will be summarised in a narrative review where qualitative analysis is not possible., Discussion: This review aims to collate the current evidence base regarding the use of patches to augment rotator cuff repair. The results of this review will help to develop, using consensus methods, the design of a definitive randomised trial assessing the clinical and cost-effectiveness of a patch to augment surgical repair of the rotator cuff that is both acceptable to stakeholders and is feasible., Systematic Review Registration: CRD42017057908.

Background: The benefits and risks of a single-stage medial UKA remains a subject of debate because of the theoretically higher risk of complications and specifically blood loss. The aim of this study was to evaluate the perioperative blood loss, risks and the functional results of single-stage bilateral medial Oxford Unicompartmental Knee Arthroplasty (OUKA) compared to a standard unilateral medial OUKA procedure (control group)., Hypothesis: The blood loss observed during bilateral single-stage medial Oxford UKA is not different from that of the control group., Methods: In this case-control prospective study, fifty patients (100 knees) who underwent single-stage bilateral medial OUKA (study group) were compared to a hundred patients (100 knees) with unilateral medial OUKA (control group), performed by the same surgeon. The real blood loss (in mL of hematocrit at 100%), incidence of blood transfusions, and complication rates were compared. Clinical results were assessed at 6 month and at a two-year minimum follow-up (FU) using IKS, KOOS and OKS scores, in addition to a satisfaction questionnaire., Results: Groups were deemed comparable. Concerning blood loss, no significant difference was observed compared to the control group (465mL±225 vs. 396±190; p=0.07). No difference was found, either, between groups regarding the complication rates (p=0.36), nor the clinical results (p=0.61) and patient satisfaction (p=0.23) at last FU., Conclusion: Single-stage bilateral procedure does not cause increased blood loss compared with controls. Moreover, clinical results were deemed good and excellent in spite of a slightly greater complication rate than those found in the literature but similar to controls., Level of Evidence: Case-control study, level III., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Introduction: Enhanced recovery programmes (ERPs) reduce patient morbidity and mortality, and provide significant cost savings by reducing length of stay. Currently, no uniform ERP guidelines exist for lower limb arthroplasty in the UK. The aim of this study was to identify variations in ERPs and determine adherence to local policy., Methods: Hospitals offering elective total knee arthroplasty (TKA) and total hip arthroplasty (THA) (23 and 22 centres respectively) contributed details of their ERPs, and performed an audit (15 patients per centre) to assess compliance., Results: Contrasting content and detail of ERPs was noted across centres. Adherence to ERPs varied significantly (40-100% for TKA, 17-94% for THA). Analysis identified perioperative use of dexamethasone, tranexamic acid and early mobilisation for TKA, and procedures performed in teaching hospitals for THA as being associated with a reduced length of stay., Conclusions: This study highlights variation in practice and poor compliance with local ERPs. Given the proven benefits of ERPs, evidence-based guidelines in the context of local skillsets should be established to optimise the patient care pathway.

Pericardial effusions arise as an extra-articular manifestation of rheumatoid arthritis (RA). Pericardial effusions are often asymptomatic, particularly in the early phase, but patients are at risk of cardiac tamponade as the effusion progresses. We discuss the case of a 40-year-old male ultramarathon runner with RA who presented with mild pleuritic chest pain and exertional dyspnoea after a recent long-haul flight. Despite a relative tachycardia, his observations were otherwise unremarkable. His blood tests revealed a C-reactive protein (CRP) of 86 mg/L and an anti-cyclic citrullinated peptide (anti-CCP) titre of 360 units/mL. He was initially diagnosed with a pulmonary embolism; however, a large pericardial effusion was found incidentally on CT pulmonary angiogram with over 1500 mL subsequently drained. The patient's symptoms resolved and CRP normalised 2 weeks later. This unique case illustrates that physically fit patients may physiologically compensate for large pericardial effusions and that arthritic symptoms do not correlate with the severity of extra-articular features in RA., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: All-suture anchors are increasingly used in rotator cuff repair procedures. Potential benefits include decreased bone damage. However, there is limited published evidence for the relative strength of fixation for all-suture anchors compared with traditional anchors., Materials and Methods: A total of four commercially available all-suture anchors, the 'Y-Knot' (ConMed), Q-FIX (Smith & Nephew), ICONIX (Stryker) and JuggerKnot (Zimmer Biomet) and a traditional anchor control TWINFIX Ultra PK Suture Anchor (Smith & Nephew) were tested in cadaveric human humeral head rotator cuff repair models (n = 24). This construct underwent cyclic loading applied by a mechanical testing rig (Zwick/Roell). Ultimate load to failure, gap formation at 50, 100, 150 and 200 cycles, and failure mechanism were recorded. Significance was set at p < 0.05., Results: Overall, mean maximum tensile strength values were significantly higher for the traditional anchor (181.0 N, standard error (se) 17.6) compared with the all-suture anchors (mean 133.1 N se 16.7) (p = 0.04). The JuggerKnot anchor had greatest displacement at 50, 100 and 150 cycles, and at failure, reaching statistical significance over the control at 100 and 150 cycles (22.6 mm se 2.5 versus 12.5 mm se 0.3; and 29.6 mm se 4.8 versus 17.0 mm se 0.7). Every all-suture anchor tested showed substantial (> 5 mm) displacement between 50 and 100 cycles (6.2 to 14.3).All-suture anchors predominantly failed due to anchor pull-out (95% versus 25% of traditional anchors), whereas a higher proportion of traditional anchors failed secondary to suture breakage., Conclusion: We demonstrate decreased failure load, increased total displacement, and variable failure mechanisms in all-suture anchors, compared with traditional anchors designed for rotator cuff repair. These findings will aid the surgeon's choice of implant, in the context of the clinical scenario.Cite this article: N. S. Nagra, N. Zargar, R. D. J. Smith, A. J. Carr. Mechanical properties of all-suture anchors for rotator cuff repair. Bone Joint Res 2017;6:82-89. DOI: 10.1302/2046-3758.62.BJR-2016-0225.R1., (© 2017 Nagra et al.)

Objectives: The aim of this study was to analyze the changes in hemoglobin level and to determine a suitable timeline for post-operative hemoglobin monitoring in patients undergoing fixation of femoral neck fracture., Patients and Methods: Patients who underwent either dynamic hip screw (DHS) fixation (n = 74, mean age: 80 years) or hip hemiarthroplasty (n = 104, mean age: 84 years) for femoral neck fracture were included into the study. The hemoglobin level of the patients was monitored perioperatively., Results: Analysis found a statistically and clinically significant mean drop in hemoglobin of 31.1 g/L over time from pre-operatively (D0) to day-5 post-operatively (p < 0.001), with significant reductions from D0 to day-1 and day-1 to day-2 (p < 0.001). At each post-operative time point, DHS patients had lower hemoglobin values over hemiarthroplasty patients (p = 0.046)., Conclusion: The decrease in hemoglobin in the first 24-h post-operative period (D0 to day-1) is an underestimation of the ultimate lowest value in hemoglobin found at day-2. Relying on the day-1 hemoglobin could be detrimental to patient care. We propose a method of predicting patients likely to be transfused, and recommend a protocol for patients undergoing femoral neck fracture surgery to standardize postoperative hemoglobin monitoring., Level of Evidence: Level IV Prognostic study., (Copyright © 2016 Turkish Association of Orthopaedics and Traumatology. Production and hosting by Elsevier B.V. All rights reserved.)

Study Design: Narrative review., Objective: The study aims to critically review the outcomes associated with the surgical repair or conservative management of spondylolysis in athletes., Methods: The English literature listed in MEDLINE/PubMed was reviewed to identify related articles using the term "spondylolysis AND athlete." The criteria for studies to be included were management of spondylolysis in athletes, English text, and no year, follow-up, or study design restrictions. The references of the retrieved articles were also evaluated. The primary outcome was time to return to sport. This search yielded 180 citations, and 25 publications were included in the review., Results: Treatment methods were dichotomized as operative and nonoperative. In the nonoperative group, 390 athletes were included. A combination of bracing with physical therapy and restriction of activities was used. Conservative measures allowed athletes to return to sport in 3.7 months (weighted mean). One hundred seventy-four patients were treated surgically. The most common technique was Buck's, using a compression screw (91/174). All authors reported satisfactory outcomes. Time to return to play was 7.9 months (weighted mean). There were insufficient studies with suitably homogenous subgroups to conduct a meta-analysis., Conclusion: There is no gold standard approach for the management of spondylolysis in the athletic population. The existing literature suggests initial therapy should be a course of conservative management with thoracolumbosacral orthosis brace, physiotherapy, and activity modification. If conservative management fails, surgical intervention should be considered. Two-sided clinical studies are needed to determine an optimal pathway for the management of athletes with spondylolysis.

Objective: The aim of this study was to analyze the changes of hemoglobin levels in patients undergoing fixation for femoral neck fracture., Methods: Peroperative hemoglobin levels of patients who underwent either dynamic hip screw (DHS) fixation (n=74; mean age: 80 years) or hip hemiarthroplasty (n=104; mean age: 84 years) for femoral neck fracture was monitored., Results: There was a statistically and clinically significant mean drop of 31.1 g/L between the preoperative (D0) and postoperative Day 5 Hb levels (p<0.001), with significant reductions from D0 to Day 1 and Day 1 to Day 2 (p<0.001). At each postoperative measurement, DHS patients had lower hemoglobin values over hemiarthroplasty patients (p=0.046)., Conclusion: The decrease in hemoglobin in the first 24-hour postoperative period (D0 to Day 1) is an underestimation of the ultimate lowest value in hemoglobin found at Day 2. Relying on the Day 1 hemoglobin level could be detrimental to patient care. We propose a method of predicting patients likely to be transfused and recommend a protocol for patients undergoing femoral neck fracture surgery to standardize postoperative hemoglobin monitoring.

Myeloid sarcoma is a rare tumour associated with acute myeloid leucaemia (AML). Infrequently, it can occur in myelodysplastic/myeloproliferative overlap syndrome conditions such as chronic monomyelocytic leucaemia (CMML), where it often heralds the transformation towards an AML. We discuss a rare presentation of myeloid sarcoma in the perianal region of a 51-year-old man, who was seen by various clinicians and treated for haemorrhoids and perianal abscess. There were no gross abnormalities in initial haematological investigations and the patient was systemically well. A histological biopsy demonstrated myeloid sarcoma and bone marrow aspirate, and trephine confirmed CMML transforming to AML. Treatment of myeloid sarcoma is dependent on whether there is associated AML in the bone marrow. Dual chemotherapy with cytarabine and daunorubicin remains the gold standard treatment in these patients. Sending histology samples of atypical lesions when performing incision and drainage procedures is extremely important, as it contributes to early detection of rare and malignant tissue diagnoses., (2015 BMJ Publishing Group Ltd.)

Intervertebral disc (IVD) cells derived from degenerate tissue respond aberrantly to mechanical stimuli, potentially due to altered mechanotransduction pathways. Elucidation of the altered, or alternative, mechanotransduction pathways operating with degeneration could yield novel targets for the treatment of IVD disease. Our aim here was to investigate the involvement of RGD-recognising integrins and associated signalling molecules in the response to cyclic tensile strain (CTS) of human annulus fibrosus (AF) cells derived from non-degenerate and degenerate IVDs. AF cells from non-degenerate and degenerate human IVDs were cyclically strained with and without function blocking RGD - peptides with 10% strain, 1.0 Hz for 20 minutes using a Flexercell® strain device. QRT-PCR and Western blotting were performed to analyse gene expression of type I collagen and ADAMTS -4, and phosphorylation of focal adhesion kinase (FAK), respectively. The response to 1.0 Hz CTS differed between the two groups of AF cells, with decreased ADAMTS -4 gene expression and decreased type I collagen gene expression post load in AF cells derived from non-degenerate and degenerate IVDs, respectively. Pre-treatment of non-degenerate AF cells with RGD peptides prevented the CTS-induced decrease in ADAMTS -4 gene expression, but caused an increase in expression at 24 hours, a response not observed in degenerate AF cells where RGD pre-treatment failed to inhibit the mechano-response. In addition, FAK phosphorylation increased in CTS stimulated AF cells derived from non-degenerate, but not degenerate IVDs, with RGD pre-treatment inhibiting the CTS - dependent increase in phosphorylated FAK. Our findings suggest that RGD -integrins are involved in the 1.0 Hz CTS - induced mechano-response observed in AF cells derived from non-degenerate, but not degenerate IVDs. This data supports our previous work, suggesting an alternative mechanotransduction pathway may be operating in degenerate AF cells.