Tendinopathy accounts for over 30% of primary care consultations and represents a growing healthcare challenge in an active and increasingly ageing population. Recognising critical cells involved in tendinopathy is essential in developing therapeutics to meet this challenge. Tendon cells are heterogenous and sparsely distributed in a dense collagen matrix; limiting previous methods to investigate cell characteristics ex vivo. We applied next generation CITE-sequencing; combining surface proteomics with in-depth, unbiased gene expression analysis of > 6400 single cells ex vivo from 11 chronically tendinopathic and 8 healthy human tendons. Immunohistochemistry validated the single cell findings. For the first time we show that human tendon harbours at least five distinct COL1A1/2 expressing tenocyte populations in addition to endothelial cells, T-cells, and monocytes. These consist of KRT7/SCX + cells expressing microfibril associated genes, PTX3 + cells co-expressing high levels of pro-inflammatory markers, APOD + fibro–adipogenic progenitors, TPPP3/PRG4 + chondrogenic cells, and ITGA7 + smooth muscle-mesenchymal cells. Surface proteomic analysis identified markers by which these sub-classes could be isolated and targeted in future. Chronic tendinopathy was associated with increased expression of pro-inflammatory markers PTX3 , CXCL1, CXCL6, CXCL8, and PDPN by microfibril associated tenocytes. Diseased endothelium had increased expression of chemokine and alarmin genes including IL33.
We investigated 29 cases, diagnosed clinically as having Morton's neuroma, who had undergone MRI and ultrasound before a neurectomy. The accuracy with which pre-operative clinical assessment, ultrasound and MRI had correctly diagnosed the presence of a neuroma were compared with one another based on the histology and the clinical outcome. Clinical assessment was the most sensitive and specific modality. The accuracy of the ultrasound and MRI was similar and dependent on size. Ultrasound was especially inaccurate for small lesions. There was no correlation between the size of the lesion and either the pre-operative pain score or the change in pain score following surgery. Reliance on single modality imaging would have led to inaccurate diagnosis in 18 cases and would have only benefited one patient. Even imaging with both modalities failed to meet the predictive values attained by clinical assessment. There is no requirement for ultrasound or MRI in patients who are thought to have a Morton's neuroma. Small lesions, < 6 mm in size, are equally able to cause symptoms as larger lesions. Neurectomy provides an excellent clinical outcome in most cases.
Advances in the design of the components for total ankle replacement have led to a resurgence of interest in this procedure. Between January 1999 and December 2004, 16 patients with a failed total ankle replacement were referred to our unit. In the presence of infection, a two-stage salvage procedure was planned. The first involved the removal of the components and the insertion of a cement spacer. Definitive treatment options included hindfoot fusion with a circular frame or amputation. When there was no infection, a one-stage salvage procedure was planned. Options included hindfoot fusion with an intramedullary nail or revision total ankle replacement. When there was suspicion of infection, a percutaneous biopsy was performed. The patients were followed up for a minimum of 12 months. Of the 16 patients, 14 had aseptic loosening, five of whom underwent a revision total ankle replacement and nine a hindfoot fusion. Of the two with infection, one underwent fusion and the other a below-knee amputation. There were no cases of wound breakdown, nonunion or malunion. Management of the failed total ankle replacement should be performed by experienced surgeons and ideally in units where multidisciplinary support is available. Currently, a hindfoot fusion appears to be preferable to a revision total ankle replacement.
The responsiveness of the Manchester-Oxford Foot Questionnaire (MOXFQ) was compared with foot/ankle-specific and generic outcome measures used to assess all surgery of the foot and ankle. We recruited 671 consecutive adult patients awaiting foot or ankle surgery, of whom 427 (63.6%) were female, with a mean age of 52.8 years (18 to 89). They independently completed the MOXFQ, Short-Form 36 (SF-36) and EuroQol (EQ-5D) questionnaires pre-operatively and at a mean of nine months (3.8 to 14.4) post-operatively. Foot/ankle surgeons assessed American Orthopaedic Foot and Ankle Society (AOFAS) scores corresponding to four foot/ankle regions. A transition item measured perceived changes in foot/ankle problems post-surgery. Of 628 eligible patients proceeding to surgery, 491 (78%) completed questionnaires and 262 (42%) received clinical assessments both pre- and post-operatively. The regions receiving surgery were: multiple/whole foot in eight (1.3%), ankle/hindfoot in 292 (46.5%), mid-foot in 21 (3.3%), hallux in 196 (31.2%), and lesser toes in 111 (17.7%). Foot/ankle-specific MOXFQ, AOFAS and EQ-5D domains produced larger effect sizes (> 0.8) than any SF-36 domains, suggesting superior responsiveness. In analyses that anchored change in scores and effect sizes to patients' responses to a transition item about their foot/ankle problems, the MOXFQ performed well. The SF-36 and EQ-5D performed poorly. Similar analyses, conducted within foot-region based sub-groups of patients, found that the responsiveness of the MOXFQ was good compared with the AOFAS. This evidence supports the MOXFQ's suitability for assessing all foot and ankle surgery.
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