The reliable production of _in vitro_ chondrocytes that faithfully recapitulate _in vivo_ development would be of great benefit for orthopaedic disease modelling and regenerative therapy(1,2). Current efforts are limited by off-target differentiation, resulting in a heterogeneous product, and by the lack of comparison to human tissue, which precludes detailed evaluation of _in vitro_ cells(3,4).

We performed single-cell RNA-sequencing of long bones dissected from first-trimester fetal limbs to form a detailed ‘atlas’ of endochondral ossification. Through 100-gene in-situ sequencing, we placed each sequenced cell type into its anatomical context to spatially resolve the process of endochondral ossification. We then used this atlas to perform deconvolution on a series of previously published bulk transcriptomes generated from _in vitro_ chondrogenesis protocols to evaluate their ability to accurately produce chondrocytes.

We then applied single-nuclear RNA-sequencing to cells from the best performing protocol collected at multiple time points to allow direct comparison between the differentiation of _in vitro_ and _in vivo_ cells.

We captured 275,000 single fetal cells, profiling the development of chondrocytes from multipotent mesenchymal progenitors to hypertrophic cells at full transcriptomic breadth. Using this atlas as the ground truth for evaluating _in vitro_ cells, we found substantial variability in cell states produced by each protocol, with many showing little similarity to _in vivo_ cells, and all exhibiting off-target differentiation.

Trajectory alignment between _in vivo_ and _in vitro_ single-cell data revealed key differences in gene expression dynamics between _in vitro_ and _in vivo cells,_ with several osteoblastic transcription factors erroneously unregulated _in vitro,_ including _FOXO1._

Using this information, we inhibited _FOXO1_ in culture to successfully increase chondrocyte yield _in vitro._

This study presents a new framework for evaluating tissue engineering protocols, using single-cell data to drive improvement and bring the prospect of true engineered cartilage closer to reality.

Excessive opioid prescriptions after total joint arthroplasty (TJA) increase risks for adverse opioid related events, chronic opioid use, and increase the availability of opioids for unlawful diversion. Thus, decreasing postoperative prescriptions may improve quality after TJA. Concerns exist that a decrease in opioids prescribed may increase complications such as readmissions, emergency department (ED) visits or worsened patient reported outcomes (PROs). The purpose of this quality improvement study was to explore whether a reduction in opioids prescribed after TJA resulted in increased complications.

Methods: Data originated from a statewide arthroplasty database (MARCQI). The database collects over 96% of all TJA performed in the state of Michigan, USA. Data was prospectively abstracted and included OMEs prescribed at discharge, readmissions, ED visits within 30 days and PROs. Data was collected one year before and after the creation of an opioid prescribing protocol that had decreased prescriptions by approximately 50% in opioid naive and tolerant patients. Trends were monitored using Shewhart control charts.

84,998 TJA over two-years were included. All groups showed a reduction in opioids prescribed. Importantly, no increased complications occurred concomitant to this reduction. No increases in ED visits or readmissions, and no decreases in KOOSJR/HOOSJR/PROMIS10 scores were noted in any of the groups.

Using large data sets and registries can drive performance and improve quality. The MARCQI Postoperative opioid prescription recommendations and performance measures decreased total oral morphine equivalents prescribed over a large and diverse population by approximately 50% without decreasing PROs or increasing ED visits or hospital readmissions. A reduction in opioids prescribed after TJA can be accomplished safely and without an increase in complications across a large population.

In 2008 The Christie was chosen by Manchester United Football Club to form a unique partnership. This funded a specialist Physiotherapist and Occupational Therapist to work exclusively on the Young Oncology Unit, creating the first posts of their kind in the UK. The YOU treats patients between 16–24 years old with a diagnosis of cancer, sarcoma being one of the most common in this age group. All patients attending the YOU now receive a fully comprehensive Physiotherapy and Occupational Therapy service to address their rehabilitation needs.

The NICE guidelines (2005) indicate that cancer care for young adults needs to be age specific, age appropriate and undertaken by appropriately trained staff; hence the importance of having specialist therapists on the YOU.

The needs of teenagers and young adults with cancer, both physically and psychologically, are more critical than at any other time in life. During their treatment patients will experience stressful events, such as alopecia, weight loss or gain, altered physical appearance, fatigue, nausea and vomiting, absence from education, and reduced contact with peers. The Physiotherapy and Occupational Therapy roles are essential in enabling young adults to adapt to their diagnosis and learn coping strategies to deal with the stressful events they encounter through their cancer experience.

During this presentation we will describe the unique role of Physiotherapy and Occupational Therapy with teenagers and young adults, using case studies to illustrate the benefits of having dedicated YOU therapists. We will also share with you the innovative ways in which the Manchester United training facilities have been used for different initiatives that have greatly benefitted and motivated our patients and their families. The partnership between two local organisations, one of the biggest football clubs in the world and a world class Cancer Centre has been a unique and positive liaison.