Razi Zaidi

The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review

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.

Levels of evidence in foot and ankle surgery literature: progress from 2000 to 2010?

BACKGROUND The focus on evidence-based medicine has led to calls for increased levels of evidence in surgical journals. The purpose of the present study was to review the levels of evidence in articles published in the foot and ankle literature and to assess changes in the level of evidence over a decade. METHODS All of the articles in the literature from the years 2000, 2005, and 2010 in Foot & Ankle International and Foot and Ankle Surgery, as well as all foot and ankle articles from The Journal of Bone and Joint Surgery (JBJS, American [A] and British [B] Volumes) were analyzed. Animal, cadaver, and basic science articles; editorials; surveys; special topics; letters to the editor; and correspondence were excluded. Articles were ranked by a five-point level-of-evidence scale, according to guidelines from the Centre for Evidence-Based Medicine. RESULTS A total of 720 articles from forty-three different countries were analyzed. The kappa value for interobserver reliability showed very good agreement between the reviewers for types of evidence (κ = 0.816 [p < 0.01]) and excellent agreement for levels of evidence (κ = 0.869 [p < 0.01]). Between 2000 and 2010, the percentage of high levels of evidence (Levels I and II) increased (5.2% to 10.3%) and low levels of evidence (Levels III, IV, and V) decreased (94.8% to 89.7%). The most frequent type of study was therapeutic. The JBJS-A produced the highest proportion of high levels of evidence. CONCLUSION 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.

Comparison of Three Different Fixation Methods of Calcaneal Osteotomies

Background: There are various methods available to fix a calcaneal osteotomy, ranging from screws to plates and staples. It is not clear if one method is superior to the other. In this series we compare the complications and union rates of 3 different methods of fixation. Methods: A retrospective review of the records of a consecutive series of patients who had a calcaneal osteotomy was undertaken. All patients had their osteotomy by the same technique, however the subsequent fixation was performed using 3 different methods: a lateral locking plate, a headless, or a headed screw. The screws were placed through a separate stab incision inserted from the infero-posterior heel. Records were kept of subsequent symptoms from the hardware and need for hardware removal as well as any complications. When screws were inserted, the entry point in relation to the weight-bearing surface of the calcaneus was also recorded. Sixty-seven osteotomies were investigated, of which 17 were fixed using a headed screw, 18 using a headless screw, and the remaining 32 were fixed using a lateral plate. Results: There was an overall 97% union rate. The only 2 cases of delayed union were both fixed using a lateral plate. Overall, 47% of the headed screws, 11% of the headless screws, and 6% of the lateral plates were removed to address symptoms that were suspected to arise from the hardware. There was a 10% rate of wound complication in the lateral plate cohort. There were no cases of sural nerve injury or neuroma. No correlation was found between entry position of screw and subsequent hardware symptoms. Conclusions: Calcaneal osteotomies have high union rates regardless of fixation method. Fixation using a headed screw is associated with a high rate of secondary screw removal. This was unrelated to the position of the screw in relation to the weight-bearing surface of the calcaneus in our series. Hardware problems were less frequent in the headless screw or the lateral plate groups; however, the incidence of local wound complications and radiological delayed union was higher in the group fixed with a lateral plate. This may be related to the greater soft tissue dissection and lesser compression achieved at the osteotomy site. Level of Evidence: Level III, retrospective case control study.

Ankle Arthroscopy A Study of Tourniquet Versus No Tourniquet

Background: More than 10 000 ankle arthroscopy procedures are performed in the United Kingdom annually. Tourniquet use is thought to allow improved visibility and reduce operative time. However this is not without risk as it predisposes to neurovascular injury. The purpose of our study was to establish the feasibility of a subsequent larger randomized controlled trial, to test the hypothesis that tourniquet use might be unnecessary in ankle arthroscopy. Methods: We performed a prospective nonrandomized case control study on 63 patients undergoing ankle arthroscopy to assess the feasibility of a randomized control trial comparing tourniquet versus no tourniquet. All patients had a tourniquet placed on the thigh and a standard arthroscopic technique. In 1 group (n = 31) the tourniquet was routinely inflated, whereas in a second group (n = 32) the tourniquet was not inflated. Demographic data, intraoperative fluid pressures, and visibility were recorded, as were any intraoperative or postoperative complications. Results: There were no significant differences between the 2 groups with respect to duration of operation, maximum intraoperative fluid pressures or visibility, and postoperative complications. In no cases where a tourniquet was not used did the surgeon need to inflate the tourniquet during the case. Conclusion: Most orthopaedic surgeons continue to use a tourniquet routinely for ankle arthroscopy, presumably on the belief that a clear operative view can be achieved only with a tourniquet. The findings of our feasibility study revealed that ankle arthroscopy was possible without the use of a tourniquet. We propose a randomized clinical trial to determine the best option for patient care. Level of Evidence: Level III, comparative series.

How do patients with end-stage ankle arthritis decide between two surgical treatments? A qualitative study

Objective To examine how patients decide between ankle fusion and ankle replacement in end-stage ankle arthritis. Design Purposive patient selection, semistructured interviews, thematic analysis. Setting Royal National Orthopaedic Hospital, Stanmore, UK. Participants 14 patients diagnosed with end-stage ankle osteoarthritis. Results We interviewed 6 men and 8 women with a mean age of 58 years (range 41–83). All had opted for surgery after failure of at least 6 months of conservative management, sequentially trading-off daily activities to limit the evolving pain. To decide between two offered treatments of ankle fusion and total ankle replacement (TAR), three major sources informed the patients’ decision-making process: their surgeon, peers and the internet. The treating surgeon was viewed as the most reliable and influential source of information. Information gleaned from other patients was also important, but with questionable reliability, as was information from the internet, both of which invariably required validation by the surgeon and in some cases the general practitioner. Conclusions Patients seek knowledge from a wealth of sources including the internet, web forums and other patients. While they leverage each of these sources to guide decision-making, the most important and influential factor in governing how patients decide on any particular surgical intervention is their surgeon. A high quality doctor–patient relationship, coupled with clear, balanced and complete information is essential to enable shared decision-making to become a standard model of care.

Quality measures for total ankle replacement, 30-day readmission and reoperation rates within 1 year of surgery: a data linkage study using the NJR data set.

Objective To report on the rate of 30-day readmission and the rate of additional or revision surgery within 12 months following total ankle replacement (TAR). Design A data-linkage study of the UK National Joint Registry (NJR) data and Hospital Episodes Statistics (HES) database. These two databases were linked in a deterministic fashion. HES episodes 12 months following the index procedure were isolated and analysed. Logistic regression was used to model predictors of reoperation and revision for primary ankle replacement. Participants All patients who underwent primary and revision ankle replacements according to the NJR between February 2008 and February 2013. Results The rate of 30-day readmission following primary and revision ankle replacement was 2.2% and 1.3%, respectively. In the 12 months following primary and revision ankle replacements, the revision rate (where implants needed to be removed) was 1.2% with increased odds in those orthopaedic units preforming <20 ankle replacements per year and patients with a preoperative fixed equinus deformity. The reoperation other than revision (where implants were not removed) in the 12 months following primary and revision TARs was 6.6% and 9.3%, respectively. Rheumatoid arthritis, cemented prosthesis and high ASA grade significantly increased the odds of reoperation. Conclusions TAR has a 30-day readmission rate of 2.2%, which is similar to that of knee replacement but lower than that of total hip replacement. 6.6% of patients undergoing primary TAR require a reoperation within 12 months of the index procedure. Early revision rates are significantly higher in low-volume centres.

Pulmonary embolism and mortality following total ankle replacement: a data linkage study using the NJR data set

Objective To determine the mortality rate following total ankle replacement (TAR) and incidence of 90 day pulmonary embolism (PE) along with the associated risk factors. Design Data-linkage study of the UK National Joint Registry (NJR) data and Hospital Episodes Statistics (HES) database. Linkage was performed in a deterministic fashion. HES episodes 90 days after the index procedure were analysed for PE. Mortality data were obtained pertaining to all the index procedures from the NJR for analysis. Participants All primary and revision ankle replacement patients captured on the NJR between February 2008 and February 2013. Results The 90-day mortality following TAR was 0.13% (95% CI 0.03 to 0.52) and 1-year mortality was 0.72% (95% CI 0.40 to 1.30); no deaths were as a result of PE. The incidence of PE within 90 days following primary TAR was 0.51% (95% CI 0.23 to 1.13). There was only one PE following revision surgery. Patients with an Royal College of Surgeons Charlson score greater than zero were at 13 times greater risk of PE (p=0.003). Conclusions There is low incidence of PE following TAR, but multiple comorbidities are a leading risk factor for its occurrence.

Total ankle replacement versus arthrodesis (TARVA): protocol for a multicentre randomised controlled trial

Introduction Total ankle replacement (TAR) or ankle arthrodesis (fusion) is the main surgical treatments for end-stage ankle osteoarthritis (OA). The popularity of ankle replacement is increasing while ankle fusion rates remain static. Both treatments have efficacy but to date all studies comparing the 2 have been observational without randomisation, and there are no published guidelines as to the most appropriate management. The TAR versus arthrodesis (TARVA) trial aims to compare the clinical and cost-effectiveness of TAR against ankle arthrodesis in the treatment of end-stage ankle OA in patients aged 50–85 years. Methods and analysis TARVA is a multicentre randomised controlled trial that will randomise 328 patients aged 50–85 years with end-stage ankle arthritis. The 2 arms of the study will be TAR or ankle arthrodesis with 164 patients in each group. Up to 16 UK centres will participate. Patients will have clinical assessments and complete questionnaires before their operation and at 6, 12, 26 and 52 weeks after surgery. The primary clinical outcome of the study is a validated patient-reported outcome measure, the Manchester Oxford foot questionnaire, captured preoperatively and 12 months after surgery. Secondary outcomes include quality-of-life scores, complications, revision, reoperation and a health economic analysis. Ethics and dissemination The protocol has been approved by the National Research Ethics Service Committee (London, Bloomsbury 14/LO/0807). This manuscript is based on V.5.0 of the protocol. The trial findings will be disseminated through peer-reviewed publications and conference presentations. Trial registration number NCT02128555.

Knee surgery and its evidence base

INTRODUCTION Evidence driven orthopaedics is gaining prominence. It enables better management decisions and therefore better patient care. The aim of our study was to review a selection of the leading publications pertaining to knee surgery to assess changes in levels of evidence over a decade. METHODS Articles from the years 2000 and 2010 in The Knee, the Journal of Arthroplasty, Knee Surgery, Sports Traumatology, Arthroscopy, the Journal of Bone and Joint Surgery (American Volume) and the Bone and Joint Journal were analysed and ranked according to guidelines from the Centre for Evidence-Based Medicine. The intervening years (2003, 2005 and 2007) were also analysed to further define the trend. RESULTS The percentage of high level evidence (level I and II) studies increased albeit without reaching statistical significance. Following a significant downward trend, the latter part of the decade saw a major rise in levels of published evidence. The most frequent type of study was therapeutic. CONCLUSIONS Although the rise in levels of evidence across the decade was not statistically significant, there was a significant drop and then rise in these levels in the interim. It is therefore important that a further study is performed to assess longer-term trends. Recent developments have made clear that high quality evidence will be having an ever increasing influence on future orthopaedic practice. We suggest that journals implement compulsory declaration of a published studys level of evidence and that authors consider their study designs carefully to enhance the quality of available evidence.

Talectomy and Tibiocalcaneal Arthrodesis in Adult Complex Hindfoot Reconstruction

Single-stage total talectomy with tibiocalcaneal arthrodesis can restore excellent function in adult patients with severe rigid, unbraceable hindfoot deformities. Talectomy allows adequate soft tissue decompression and correction of bony malalignment, restoring stability to the hindfoot axis on weight bearing. We performed single-stage total talectomy with tibiocalcaneal arthrodesis on 13 feet in 12 patients (6F; 6M) with an average age of 67 years (range, 54 to 77 y). Fusion was achieved in 9 feet (69%) at an average time of 21 weeks. In the remaining 4 feet, in which consolidation of the fusion was not achieved, the deformity remained corrected and this allowed the patients to mobilize in braces. Average duration of follow-up was 21 months (range, 12 to 52 mo). All patients had a stable, plantigrade, braceable foot and were community or household ambulators. Our data suggests that this procedure should be added to the armamentarium of procedures to salvage severe hindfoot deformities.