To evaluate if clinical recovery following midshaft clavicle fracture is associated with nonunion and determine if this has superior predictive value compared to estimation at time of injury.

A prospective study of all patients (≥16 years) who sustained a displaced midshaft clavicle fracture was performed. We assessed patient demographics, injury factors, functional scores and radiographic predictors with a standardized protocol at six-weeks. Conditional-stepwise regression was used to assess which factors independently predicted nonunion at six-months post-injury determined by CT. The nonunion predictor six-week model (NUP6) was compared against a previously validated model based on factors available at time of injury (NUP0-smoking, comminution and fracture displacement).

200 patients completed follow-up at six months. The nonunion rate was 14% (27/200). Of the functional scores, the QuickDASH had the highest accuracy on receiver-operator-characteristic (ROC) curve analysis with a 39.8 threshold, above which was associated with nonunion (Area Under Curve (AUC) 76.8%, p<0.001).

On regression modelling QuickDASH ≥40 (p=0.001), no callus on radiograph (p=0.004) and fracture movement on examination (p=0.001) were significant predictors of nonunion. If none were present the predicted nonunion risk was 3%, found in 40% of the cohort (n=80/200). Conversely if two or more were present, found in 23.5% of the cohort, the predicted nonunion risk was 60%.

The NUP6 model appeared to have superior accuracy when compared to the NUP0 model on ROC curve analysis (AUC 87.3% vs 64.8% respectively).

Delayed assessment at six-weeks following displaced clavicle fracture enables a more accurate prediction of fracture healing.

Scar tissue formation secondary to acute muscle injury, surgical wounding and compartment syndrome can result in significant functional impairment and predispose to further injury. The source of fibroblasts, and the molecular mechanisms driving their activation and persistence in skeletal muscle fibrosis are not known. We hypothesized that cells expressing PDGFRβ become fibroblasts in response to injury and that targeting αv integrins in these cells reduces skeletal muscle fibrosis.

We used double-fluorescent reporter mice to demonstrate that cells expressing PDGFRβ become activated myofibroblasts in response to cardiotoxin (CTX) induced skeletal muscle injury. Following injury, PDGFRβ+ cells moved from perivascular locations into the interstitium in a distribution characteristic of fibroblasts, and showed marked induction of fibroblastic genes including αSMA and collagen1 (all p<0.0001). To confirm that αv integrins present on PDGFRβ cells critically regulate skeletal muscle fibrosis we used Itgavflox/flox;PDGFRβ-Cre mice (transgenic mice in which αv integrins are ‘knocked-down’ in PDGFRβ+ cells). These mice were significantly protected from CTX induced fibrosis (p<0.01). To demonstrate potential clinical utility of targeting αv integrins, we used a small molecule inhibitor of αv integrins (CWHM12). Treatment with CWHM12 significantly reduced fibrosis when delivered from the time of injury (p<0.01) and when delivered after the fibrotic response had become established (p<0.01).

We have identified a core pathway regulating fibrosis in skeletal muscle. Pharmacologic inhibition of αv integrins has potential clinical utility in the treatment and prevention of skeletal muscle fibrosis.

Our unpublished data has indicated that the perivascular stem cells (PSCs) have increased chondrogenic potential compared to mesenchymal stem cells (MSCs) derived in culture. There has been a recent change in the theory that stem cells work by a paracrine effect rather than differentiation. There are minimal data demonstrating the persistence of implanted stem cells when used for engraftment. This study aimed to develop an autologous large animal model for perivascular stem cells as well as to determine if cells were retained in the articular cartilage defects.

The reactivity of anti-human and anti-ovine antibodies was ascertained using immunohistochemistry and fluorescence-activated cell sorting (FACS). A panel of antibodies were combined and used to identify and purify pericytes (CD34-CD45-CD146+) and adventitial cells (CD34+CD45-CD146-) using FACS. The purified cells were cultured and their identity checked using FACS. These cultured cells demonstrated osteogenic, adipogenic and chondrogenic potential.

Autologous ovine PSCs (oPSCs) were isolated, cultured and transfected using a GFP virus. The transfection rate was 88%. The cells were implanted into an articular cartilage defect on the medial femoral condyle using a hydrogel, four weeks following implantation the condyle was explanted and confocal laser scanning microscopy demonstrated the presence of oPSCs in the defect. Histology did not demonstrate any repair tissue at this early time point.

These data have confirmed the viability our large animal model and that the implanted stem cells were retained in the defect four weeks following implantation.

The aim was to perform a cost-utility analysis of total joint replacement in the current environment.

Arthritis is a disabling condition that leads to long-term deterioration in quality of life. Total joint replacement, despite being one of the greatest advances in medicine in the modern era, has come under recent scrutiny. The National Health Service (NHS) has competing demands and resource allocation is challenging in times of economic restraint.

Patients undergoing total hip (n=348) and knee arthroplasty (n=323), from January to July 2010, were entered into a prospective arthroplasty database. A health utility score was derived from the Euroqol (EQ-5D) score preoperatively, and at one year, and was combined with individual life expectancy to derive the Quality-Adujusted-Life-Years (QALYs) gained. Predicted need for revision surgery was Incorporated in the model. The 2011–12 Scottish Tariff was used. Two-way analysis of variance was used to compare QALYs gained between procedures, while controlling for baseline differences.

The number of QALYs gained was higher in THR versus TKR (6.53 vs 4.04 years, p<0.001). The cost per QALY for THR was £1371 (95% CI £1194 to £1614) compared with £2101 (£1762 to £2620) for TKR. Predictors of an increase in QALYs gained were poorer health prior to surgery (p<0.001) and younger age (p<0.001). General health (EQ-5D VAS) showed greater improvement in THR versus TKR (p<0.001).

This study provides up to date cost-effectiveness data for total joint replacement. THR and TKR are both extremely clinically and cost-effective interventions, with costs that compare favourably with other medical interventions (e.g. laparoscopic hernia repair vs open: £55,548 per QALY; CHD primary prevention with statins: £21,000).