BackgroundThe management of articular cartilage defects presents many clinical challenges due to its avascular, aneural and alymphatic nature. Bone marrow stimulation techniques, such as microfracture, are the most frequently used method in clinical practice however the resulting mixed fibrocartilage tissue which is inferior to native hyaline cartilage. Other methods have shown promise but are far from perfect. There is an unmet need and growing interest in regenerative medicine and tissue engineering to improve the outcome for patients requiring cartilage repair. Many published reviews on cartilage repair only list human clinical trials, underestimating the wealth of basic sciences and animal studies that are precursors to future research. We therefore set out to perform a systematic review of the literature to assess the translation of stem cell therapy to explore what research had been carried out at each of the stages of translation from bench-top (in vitro), animal (pre-clinical) and human studies (clinical) and assemble an evidence-based cascade for the responsible introduction of stem cell therapy for cartilage defects.Main body of abstractThis review was conducted in accordance to PRISMA guidelines using CINHAL, MEDLINE, EMBASE, Scopus and Web of Knowledge databases from 1st January 1900 to 30th June 2015. In total, there were 2880 studies identified of which 252 studies were included for analysis (100 articles for in vitro studies, 111 studies for animal studies; and 31 studies for human studies). There was a huge variance in cell source in pre-clinical studies both of terms of animal used, location of harvest (fat, marrow, blood or synovium) and allogeneicity. The use of scaffolds, growth factors, number of cell passages and number of cells used was hugely heterogeneous.Short conclusionsThis review offers a comprehensive assessment of the evidence behind the translation of basic science to the clinical practice of cartilage repair. It has revealed a lack of connectivity between the in vitro, pre-clinical and human data and a patchwork quilt of synergistic evidence. Drivers for progress in this space are largely driven by patient demand, surgeon inquisition and a regulatory framework that is learning at the same pace as new developments take place.
Level III, retrospective case control study.
We performed a systematic review and meta-analysis of modern total ankle replacements (TARs) to determine the survivorship, outcome, complications, radiological findings and range of movement, in patients with end-stage osteoarthritis (OA) of the ankle who undergo this procedure. We used the methodology of the Cochrane Collaboration, which uses risk of bias profiling to assess the quality of papers in favour of a domain-based approach. Continuous outcome scores were pooled across studies using the generic inverse variance method and the random-effects model was used to incorporate clinical and methodological heterogeneity. We included 58 papers (7942 TARs) with an interobserver reliability (Kappa) for selection, performance, attrition, detection and reporting bias of between 0.83 and 0.98. The overall survivorship was 89% at ten years with an annual failure rate of 1.2% (95% confidence interval (CI) 0.7 to 1.6). The mean American Orthopaedic Foot and Ankle Society score changed from 40 (95% CI 36 to 43) pre-operatively to 80 (95% CI 76 to 84) at a mean follow-up of 8.2 years (7 to 10) (p < 0.01). Radiolucencies were identified in up to 23% of TARs after a mean of 4.4 years (2.3 to 9.6). The mean total range of movement improved from 23° (95% CI 19 to 26) to 34° (95% CI 26 to 41) (p = 0.01). Our study demonstrates that TAR has a positive impact on patients' lives, with benefits lasting ten years, as judged by improvement in pain and function, as well as improved gait and increased range of movement. However, the quality of evidence is weak and fraught with biases and high quality randomised controlled trials are required to compare TAR with other forms of treatment such as fusion.
There has been a trend toward higher levels of evidence in foot and ankle surgery literature over a decade, but the differences did not reach significance.
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