It is undetermined which factors predict return to work following arthroscopic rotator cuff repair. We aimed to identify which factors predicted return to work at any level, and return to pre-injury levels of work 6 months post-arthroscopic rotator cuff repair.

Multiple logistic regression analysis of prospectively collected demographic, pre-injury, preoperative, and intraoperative data from 1502 consecutive primary arthroscopic rotator cuff repairs, performed by a single surgeon, was performed to identify independent predictors of return to work, and return to pre-injury levels of work respectively, 6 months post-surgery.

Six months post-rotator cuff repair, 76% of patients returned to work (RTW), and 40% returned to pre-injury levels of work (Full-RTW). RTW at 6 months was likely if patients were still working after their injuries, but prior to surgery (Wald statistic [W]=55, p<0.0001), were stronger in internal rotation preoperatively (W=8, p=0.004), had full-thickness tears (W=9, p=0.002), and were female (W=5, p=0.030). Patients who achieved Full-RTW were likely to have worked less strenuously pre-injury (W=173, p<0.0001), worked more strenuously post-injury but pre-surgery (W=22, p<0.0001), had greater behind-the-back lift-off strength preoperatively (W=8, p=0.004), and had less passive external rotation range of motion preoperatively (W=5, p=0.034). Patients who were still working post-injury, but pre-surgery were 1.6-times more likely to RTW than patients who were not (p<0.0001). Patients who nominated their pre-injury level of work as “light” were 11-times more likely to achieve Full-RTW than those who nominated “strenuous” (p<0.0001).

Six months post-rotator cuff repair, a higher patient-rated post-injury, but pre-surgery level of work was the strongest predictor of RTW. A lower patient-rated pre-injury level of work was the strongest predictor of Full-RTW. Greater preoperative subscapularis strength independently predicted both RTW, and Full-RTW.

Alarmins- also referred to as damage associated molecular patterns (DAMPS)- are endogenous molecules mobilized in response to tissue damage known to activate the innate immune system and regulate tissue repair and remodelling. The molecular mechanisms that regulate inflammatory and remodelling pathways in tendinopathy are largely unknown therefore identifying early immune effectors is essential to understanding the pathology. S100A8 and S100A9 are low molecular weight calcium binding proteins primarily released by activated phagocytes in an inflammatory setting and also secreted as a heterodimeric complex that exhibits cytokine like functions. Based on our previous investigations we sought evidence of S100A8/A9 expression in human tendinopathy and thereafter, to explore mechanisms whereby S100 proteins may regulate inflammatory mediators and matrix regulation in human tenocytes.

Torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing ‘early pathology’) biopsies were collected from patients undergoing arthroscopic shoulder surgery. Control samples of subscapularis tendon were collected from patients undergoing arthroscopic stabilisation surgery. S100A8/A9 expression was analysed at transcript and protein level using quantitative RT-PCR and immunohistochemistry, respectively. Primary human tenocytes were cultured from hamstring tendon tissue obtained during hamstring tendon ACL reconstruction. The in vitro effect of recombinant human S100 A8/A9 on primary human tenocytes was measured using quantitative RT-PCR and ELISA.

Immunohistochemistry of tendinopathic tissues demonstrated the presence of S100 A8/A9 in diseased tissues compared to control tissue. In addition, early pathological diseased tissue indicated greater S100A9 expression compared with established diseased pathology. These findings were reflected by data obtained at transcript level from diseased tissues. Recombinant human S100A8, A9 and A8/A9 complex led to significant increase in expression of inflammatory mediators, including IL-6 in vitro. Further analysis via quantitative RT-PCR demonstrated recombinant S100A8, A9 and A8/A9 complex treatment on tenocytes, in vitro, had no direct effect on the expression of genes involved in matrix remodelling.

The presence of S100A8 and S100A9 in early tendinopathic lesions suggests expression is upregulated in response to cellular damage. S100A8 and S100A9 are endogenous ligands of Toll-like receptors (TLRs) and receptor for advanced glycation end products (RAGE). These receptors have known regulatory effects on immune mediated cytokine production. We propose S100A8 and S100A9 as active alarmins in the early stages of tendinopathy and thus targeting of its downstream signalling may offer novel therapeutic approaches in the management of human tendon disorders.

The objective was to seek evidence of hypoxia in early human tendinopathy and thereafter, to explore mechanisms whereby tissue hypoxia may regulate apoptosis, inflammatory mediators and matrix regulation in human tenocytes.

Fifteen torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing ‘early pathology’) biopsies were collected from patients undergoing arthroscopic shoulder surgery. Control samples of subscapularis tendon were collected from 10 patients undergoing arthroscopic stabilisation surgery. Markers of hypoxia were quantified by immunohistochemical methods. Human tendon-derived primary cells were derived from hamstring tendon tissue obtained during hamstring tendon ACL reconstruction. The impact of hypoxia upon tenocyte biology ex vivo was measured using quantitative RT-PCR, multiplex cytokine assays, apoptotic proteomic profiling, immunohistochemistry and annexin V FACS staining.

Increased expression of HIF 1a, Bcl-2 and clusterin (hypoxic and apoptotic markers) was detected in subscapularis tendon samples compared to both matched torn samples and non matched control samples (p<0.01). Hypoxic tenocytes exhibited increased production of proinflammatory cytokines (p<0.001), altered matrix regulation (p<0.01) with increased production of Collagen type III operating through a MAPK dependent pathway. Finally, hypoxia increased expression of several mediators of apoptosis and thereby promoted tenocyte apoptosis.

Hypoxia promotes expression of proinflammatory cytokines, key apoptotic mediators and drives matrix component synthesis towards a collagen type III profile by human tenocytes. We propose hypoxic cell injury as a critical pathophysiological mechanism in early tendinopathy offering novel therapeutic opportunities in the management of tendon disorders.

The purpose of this study was to assess the clinical outcomes of three different rotator cuff repair techniques and to correlate these results with the integrity of the cuff as determined by ultrasonographic evaluation.

Three cohorts of patients had repair of a symptomatic rotator cuff tear using:

an open technique with Mitek RC Quickanchor double row, one mattress suture per anchor (n = 49);

Standardised patient and examiner determined outcomes were obtained prospectively pre-operatively and at 6 weeks, 3 months and 6 months post-operatively. Ultrasound studies were performed with a validated protocol at 6 months post surgery.

Arthroscopic knotless repair was, on average,14 minutes faster than both open cuff repair (p< 0.001) and arthroscopic knotted repair (p< 0.01).Clinical outcomes were similar with the exception that the arthroscopic groups had, on average, 20% better ASES scores than the open group at 6 months (p< 0.001). The only complication was re-tear, which correlated with tear size (r=0.5, p< 0.001) and operation time (r=0.3, p< 0.001) and occurred more frequently following open repair (39%) compared with arthroscopic knotted (25%) and arthroscopic knotless (16%) repair (p< 0.01). The retear rates of tears > 8cm2 were significantly greater (p< 0.01) when using an open (88%) or arthroscopic knotted (67%) technique compared to the arthroscopic knotless (25%) cohort.

Rotator cuff repair, whether performed via an open or arthroscopic technique resulted in improvements in pain, motion, strength and function. An intact cuff on ultrasound corresponded to better results with regard to supraspinatus strength, patient outcomes and rotator cuff functional ability. Tears > 8cm2 fixed with an arthroscopic knotless technique had better structural outcomes at 6 months.

Rotator cuff tendons are typically reattached to the proximal humerus using either transosseous sutures or suture anchors. Their primary mode of failure is at the tendon bone interface 1. Surgical adhesives are used to bond cartilage, tendons and bone, and to close wounds. In an attempt to increase the tendon-bone interface we investigated the addition of a novel adhesive secreted from a species of Australian frog (Notaden bennetti) 2 to different methods of rotator cuff repair.

Forty two fresh frozen sheep infraspinatus tendons were repaired using 3 different techniques: transosseous sutures; two Mitek RC Quickanchors with 1 suture per anchor and two Opus Magnum anchors with 1 suture per anchor all using a mattress stitch configuration. In each group 7 shoulders were repaired with the addition of a small amount of frog glue to the infraspinatus footprint while 7 were used as control with no adhesive. Mechanical testing was performed using a mechanical tensile testing machine.

The strongest construct in the control groups was the Mitek suture anchors (mean 86±5 N) followed by the Opus suture anchor (69±6N) and transosseous repair (50±6N). This proved significant (p< 0.05) between both metallic anchors and the transosseous repair.{BR}The addition of frog glue resulted in a significant increase in load to failure and total energy required until failure in all repair techniques (p< 0.01). There was a 2 fold increase in load to failure of both the Opus Magnum (143±8N) and Mitek RC Fastin (165N±20 N) anchors while the transosseous repair (86± 8 N) had a 1.7 fold increase in its load to failure.

This data suggests that:

suture anchor fixation is a stronger construct requiring a larger amount of total force to fail than transosseous repair using a one suture repair technique, that

The unique properties of this frog glue (strong, flexible, sets in water and biocompatibility) may ultimately lead to the production of a useful adjunct for rotator cuff repair in humans.

Excessive apoptosis has been found in torn supraspinatus tendon1 and mechanically loaded tendon cells2. Following oxidative and other forms of stress, one family of proteins that is often unregulated are Heat Shock Proteins (HSPs). The purpose of this study was to determine if HSPs were unregulated in human and rat models of tendinopathy and to determine if this was associated with increased expression of regulators of apoptosis (cFLIP, Caspases 3& 8).

A running rat supraspinatus tendinopathy overuse model 3 was used with custom microarrays consisting of 5760 rat oligonucleotides in duplicate. Seventeen torn supraspinatus tendon and matched intact subscapularis tendon samples were collected from patients undergoing arthroscopic shoulder surgery. Control samples of subscapularis tendon were collected from ten patients undergoing arthroscopic stabilisation surgery and evaluated using semiquantative RT-PCR and immunohistochemistry.

Rat Microarray: Upregulation of HSP 27 (×3.4) & 70 (×2.5) and cFLIP (×2.2) receptor was noted in degenerative rat supraspinatus tendon subjected to daily treadmill running for 14 days compared to tendons of animals subject to cage activity only. Histological analysis: All torn human supraspinatus tendons exhibited changes consistent with marked tendinopathy. Matched subscapularis tendon showed appearances of moderate-advanced degenerative change. Apoptosis mRNA expression: The expression levels of caspase 3 & 8 and HSPs 27 & 70 were significantly higher in the torn edges of supraspinatus when compared to matched subscapularis tendon and control tendon (p< 0.01). cFLIP showed significantly greater (p< 0.001) expression in matched subscapularis compared to supraspinatus and control tendon. Immunohistochemical analysis: cFLIP, Caspase 3 & 8 and HSP 27 and 70 was confirmed in all samples of torn supraspinatus tendon. Significantly increased immunoactivity of Caspase 3& 8 and HSP 27 & 70 were found in torn supraspinatus (p< 0.001) compared to matched and normal subscapularis. The proteins were localized to tendon cells.

The finding of significantly increased levels of Heat Shock Proteins in human and rat models of tendinopathy with the co-expression of other regulators of apoptosis suggests that Heat Shock Proteins play a role in the cascade of stress activated-programmed cell death and degeneration in tendinopathy.

Aim: The purpose of this study was to evaluate the cytokine molecules present in a rat tendinopathy model and in the torn edge of human rotator cuff tendon in an attempt to understand their role in tendon degeneration.

Methods: A rat tendon overuse model was used with custom microarrays consisting of 5760 rat oligonucleotide features in duplicate. Seventeen torn supraspinatus tendon and matched intact subscapularis tendon samples were collected from patients undergoing arthroscopic shoulder surgery.Control samples of subscapularis tendon were collected from ten patients undergoing arthroscopic stabilisation surgery.Specimens were analysed for the presence of interleukins 18, 15, 12, 11, 6, 2, macrophage inhibitory factor (MIF), and tumour necrosis factor Ą by semiquantitative RT-PCR and immunohistochemistry. Tendinopathy was assessed on a basic histological scale.

Results: Rat Microarray analysis: Upregulation of IL-6, IL-11 and IL18 receptor was noted in the degenerated rat supraspinatus tendon. Downregulation of IL-2 was noted. No other cytokine signal was expressed. Histological analysis: All torn human supraspinatus tendons changes consistent with marked tendinopathy. Matched subscapularis tendon showed appearances of moderate-advanced degenerative change. Cytokine mRNA expression: TNF-£\ mRNA expression was found to be significantly elevated (p< 0.01) in subscapularis tendon compared to torn supraspinatus samples. The expression levels of IL-18, IL-15, IL-6 and MIF was significantly higher in the torn edges of supraspinatus when compared to matched subscapularis tendon and normal control tendon (p< 0.001).

Immunohistochemical analysis: Presence of IL-18, IL-15, Il-6, MIF and TNF-£\ was confirmed in all samples of torn supraspinatus tendon. Significantly increased levels of IL-18, IL-15, IL-6 and MIF were found in torn supraspinatus. (p< 0.01) compared to matched and normal subscapularis.

Conclusions: Cytokines have been shown to promote the intensive production of reactive O2 metabolites ¹ and are potent agonists of protein kinases ². Our finding of significantly increased cytokine levels may suggest that these molecules when expressed during the degenerate and healing phases of tendon injury result in the subsequent production of reactive O2 species and protein kinases³ causing tendon damage or failure of the normal reparative process. Our finding of marked tendinopathy in matched subscapularis tendon may also provide a useful human tendinopathy model.

The fine structure of palmar fascia from patients with Dupuytren's contracture (DC) was compared with that from patients with carpal tunnel syndrome (CTS). In contrast to previous assumptions, the ultrastructure of fibroblasts both in vivo and in vitro from DC and CTS appeared identical, indicating that myofibroblasts are not specific to DC. The major differences between DC and CTS were: 1) a sixfold and fortyfold increase in fibroblast density in cord and nodular areas of DC compared with CTS; 2) a more disorganised pattern of collagen fibrils in DC; and 3) markedly narrowed microvessels surrounded by thickened, laminated basal laminae and proliferating fibroblasts in DC compared with CTS. To account for these morphological changes a hypothesis is presented which proposes that oxygen-free radicals cause pericytic necrosis and fibroblastic proliferation. This hypothesis provides a potential avenue for therapy of DC and other fibrotic conditions.