Background

Masses are not uncommon in the foot and ankle. Most of these masses are benign, often leading clinicians to underestimate their potential for malignancy.

Introduction

Primary ankle arthroplasty (TAR) is increasingly used to treat end-stage ankle arthritis. Reported revision rates of TAR vary from 8.5% to 11.1% at 9 years. Revision surgery remains technically challenging with options ranging from simple joint debridement to tibio-talar-calcaneal fusion. The efficacy of these procedures remains unclear and there is no consensus on optimal revision options.

Background

Open or arthroscopic ankle fusion (AAF) is a successful operative treatment for end-stage ankle arthritis. Evidence suggest that AAFs have better outcomes. In addition to the operative technique other patient-factors can influence outcomes. The most significant complication of ankle fusion is a non-union. To better understand the risk factors related to this we undertook a retrospective investigation of primary AAFs.

Tendinopathy can commonly occur around the foot and ankle resulting in isolated rupture, debilitating pain and degenerative foot deformity. The pathophysiology and key cells involved are not fully understood. This is partly because the dense collagen matrix that surrounds relatively few resident cells limits the ability of previous techniques to identify and target those cells of interest. In this study, we apply novel single cell RNA sequencing (CITE-Seq) techniques to healthy and tendinopathic foot/ankle tendons. For the first time we have identified multiple sub-populations of cells in human tendons. These findings challenge the view that there is a single principal tendon cell type and open new avenues for further study. Healthy tendon samples were obtained from patients undergoing tendon transfer procedures; including tibialis posterior and FHL. Diseased tendon samples were obtained during debridement of intractable Achilles and peroneal tendinopathy, and during fusion of degenerative joints. Single cell RNA sequencing with surface proteomic analysis identified 10 sub-populations of human tendon derived cells. These included groups expressing genes associated with fibro-adipogenic progenitors (FAPs) as well as ITGA7+VCAM1- recently described in mouse muscle but, as yet, not human tendon. In addition we have identified previously unrecognised sub-classes of collagen type 1 associated tendon cells. Each sub-class expresses a different set of extra-cellular matrix genes suggesting they each play a unique role in maintaining the structural integrity of normal tendon. Diseased tendon harboured a greater proportion of macrophages and cytotoxic lymphocytes than healthy tendon. This inflammatory response is potentially driven by resident tendon fibroblasts which show increased expression of pro-inflammatory cytokines. Finally, identification of a previously unknown sub-population of cells found predominantly in tendinopathic tissue offers new insight into the underlying pathophysiology. Further work aims to identify novel proteins targets for possible therapeutic pathways.

Introduction:

In April 2012 National Trauma Networks were introduced in England to optimise the management of major trauma. All patients with an ISS of ≥ 16 should be transferred to the regional Major Trauma Centre (level 1). Our hypothesis was that severe foot and ankle injuries would no longer be managed in Trauma Units (level 2).