Total Ankle Replacement Versus Arthrodesis for End-Stage Ankle Osteoarthritis: A Randomized Controlled Trial.

BACKGROUND: End-stage ankle osteoarthritis causes severe pain and disability. There are no randomized trials comparing the 2 main surgical treatments: total ankle replacement (TAR) and ankle fusion (AF). OBJECTIVE: To determine which treatment is superior in terms of clinical scores and adverse events. DESIGN: A multicenter, parallel-group, open-label randomized trial. (ISRCTN registry number: 60672307). SETTING: 17 National Health Service trusts across the United Kingdom. PATIENTS: Patients with end-stage ankle osteoarthritis, aged 50 to 85 years, and suitable for either procedure. INTERVENTION: Patients were randomly assigned to TAR or AF surgical treatment. MEASUREMENTS: The primary outcome was change in Manchester-Oxford Foot Questionnaire walking/standing (MOXFQ-W/S) domain scores between baseline and 52 weeks after surgery. No blinding was possible. RESULTS: Between 6 March 2015 and 10 January 2019, a total of 303 patients were randomly assigned; mean age was 68 years, and 71% were men. Twenty-one patients withdrew before surgery, and 281 clinical scores were analyzed. At 52 weeks, the mean MOXFQ-W/S scores improved for both groups. The adjusted difference in the change in MOXFQ-W/S scores from baseline was -5.6 (95% CI, -12.5 to 1.4), showing that TAR improved more than AF, but the difference was not considered clinically or statistically significant. The number of adverse events was similar between groups (109 vs. 104), but there were more wound healing issues in the TAR group and more thromboembolic events and nonunion in the AF group. The symptomatic nonunion rate for AF was 7%. A post hoc analysis suggested superiority of fixed-bearing TAR over AF (-11.1 [CI, -19.3 to -2.9]). LIMITATION: Only 52-week data; pragmatic design creates heterogeneity of implants and surgical techniques. CONCLUSION: Both TAR and AF improve MOXFQ-W/S and had similar clinical scores and number of harms. Total ankle replacement had greater wound healing complications and nerve injuries, whereas AF had greater thromboembolism and nonunion, with a symptomatic nonunion rate of 7%. PRIMARY FUNDING SOURCE: National Institute for Health and Care Research Heath Technology Assessment Programme.

Avoidance of injury to the posterior neurovascular bundle during total ankle arthroplasty - A simple technical tip.

Iatrogenic nerve injury to the tibial nerve is a serious but avoidable complication of total ankle replacements and may be under-reported as it may go unrecognised or thought to be due to tarsal tunnel syndrome. The tibial nerve is particularly vulnerable during the saw cuts at the posteromedial corner without appropriate protection. Prior to drilling the tibial and talar pins of the adjustment block for the Infinity ankle replacement we perform a 2 cm incision behind the medial malleolus. The tibialis posterior tendon sheath is identified and incised. A periosteal elevator is used to develop a plane between the back of the tibia and the tibialis posterior tendon and then exchanged for a mini Hohmann retractor protecting the neurovascular bundle. This allows us to drill the pins and saw cuts safely. The Hohmann retractor can be felt at the tip of the saw blade providing reassurance that the blade is not too deep. Our technique has not previously been reported in the literature. It acts as a simple reproducible way of avoiding injury to structures at the back of the ankle joint.

Fibula nail fixation in ankle fractures with significant soft tissue compromise: a retrospective cohort study.

PURPOSE: Intramedullary fixation of lateral malleolar fractures has increased in popularity recently with the introduction of the fibula nail. It has been proposed as an alternative fixation method in fractures to minimise soft tissue injury. The aim of this study was to evaluate the clinical and patient-reported outcomes of those who had an ankle fracture with concurrent significant soft tissue damage, treated with a fibula nail. METHODS: Details of patients who were managed at our institution using a fibula nail were obtained from the trauma database. The Acumed Fibula Rod System (FRS) was used in all cases. Those who were less than 12 months following injury were excluded. Patients attended a follow-up clinic for measurement of range of movement, radiographs, and to complete MOX-FQ and EQ-5D questionnaires. RESULTS: Twenty patients were identified. Eleven attended for review in person, and a further eight completed questionnaires (questionnaire response rate 95%). The mean age was 59 years (range 19-91). Twelve fractures were open, all of which were initially managed using an external fixator. One patient developed deep infection necessitating fusion. The mean MOX-FQ and EQ-5D scores were 53.6 and 0.649, respectively, at a median of 40 months post-injury. The mean EQ-VAS was 70. The range of movement of the affected side was significantly less than the unaffected side (p < 0.001 on paired t-test). CONCLUSION: This study suggests that the FRS offers a reliable and acceptable alternative fixation technique for patients who have significant soft tissue injuries.

Impacts on the metabolome of down-regulating polyphenol oxidase in potato tubers.

Tubers of potato (Solanum tuberosum L. cv. Estima) genetically modified to reduce polyphenol oxidase (PPO) activity and enzymatic discolouration were assessed for changes in the metabolome using Liquid Chromatography-Mass Spectrometry (LC-MS) and Gas Chromatography (GC)-MS. Metabolome changes induced over a 48 hour (h) period by tuber wounding (sliced transverse sections) were also assessed using two PPO antisense lines (asPPO) and a wild-type (WT) control. Data were analysed using Principal Components Analysis and Analysis of Variance to assess differences between genotypes and temporal changes post-tuber wounding (by slicing). The levels of 15 metabolites (out of a total of 134 that were detected) differed between the WT and asPPO lines in mature tubers at harvest. A considerably higher number (63) of these metabolites changed significantly over a 48 h period following tuber wounding. For individual metabolites the magnitude of the differences between the WT and asPPO lines at harvest were small compared with the impacts of tuber wounding on metabolite levels. Some of the observed metabolite changes are explicable in terms of pathways known to be affected by wound responses. Whilst some statistically significant interactions (11 metabolites) were observed between line and time after wounding, very few profiles were consistent when comparing the WT with both asPPO lines, and the underlying metabolites appeared to be random in terms of the pathways they occupy. Overall, mechanical damage to tubers has a considerably greater impact on the metabolite profile than any potential unintended effects resulting from the down-regulation of PPO gene expression.

New EU legislation for risk assessment of GM food: no scientific justification for mandatory animal feeding trials.

This commentary focuses on the potential added value of and need for (sub)-chronic testing of whole genetically modified (GM) foods in rodents to assess their safety. Such routine testing should not be required since, due to apparent weaknesses in the approach, it does not add to current risk assessment of GM foods. Moreover, the demand for routine testing using animals is in conflict with the European Union (EU) Commission's efforts to reduce animal experimentation. Regulating agencies in the EU are invited to respect the sound scientific principles applied to the risk assessment of foods derived from GM plants and not to interfere in the risk assessment by introducing extra requirements based on pseudo-scientific or political considerations.

A Comparison of Fibula Pro-Tibia Fixation Versus Hindfoot Nailing for Unstable Fractures of the Ankle in Those Older Than 60 Years.

BACKGROUND: Ankle fractures in the elderly are an increasing problem, with poor outcomes reported. Operative options for patients with suspected osteoporosis and needing to bear weight to ambulate can include hindfoot intramedullary nail (IMN) or fibula pro-tibia fixation (FPT). FPT involves passing 2 or more screws through a lateral fibula plate, crossing the fibular into the tibia, with 1 or more screws proximal to the incisura. We compared the outcomes of these 2 techniques. METHOD: A retrospective review identified 68 patients aged over 60 years with unstable ankle fractures, treated with IMN or FPT. Primary outcome was surgical reoperation/revision rate, secondary outcomes included complications, length of stay, and functional status. Results: There were no significant differences in demographics between IMN and FPT. Revision rates were higher in IMN compared with FPT (P < .0001). IMN patients postoperatively had longer hospital stays (P = .02), longer follow-up times (P = .008), and higher rates of delayed wound healing (P = .03) and nonunion (P = .001). Multivariate analysis identified fixation and age to affect revision rates. CONCLUSION: Outcomes were worse in the IMN group compared with FPT. We believe both techniques have a role in the management of elderly ankle fractures, but patient selection is key. We suggest that FPT should be the first-choice technique when soft tissues permit. LEVELS OF EVIDENCE: Level III.

Two to Five-Year Outcomes of Total Ankle Arthroplasty with the Infinity Fixed-Bearing Implant: A Concise Follow-up of a Previous Report.

LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Compositional and toxicological analysis of a GM potato line with reduced α-solanine content--a 90-day feeding study in the Syrian Golden hamster.

Steroidal glycoalkaloids (GAs) are toxins, produced by plants of the Solanaceae family. The potato plant (Solanum tuberosum L.) and its tubers predominantly contain the two GAs α-chaconine and α-solanine. These compounds are believed to act in synergy, and the degree of toxicity may therefore depend on their ratio in the potato. To determine the influence of α-solanine: α-chaconine ratio in potatoes on toxicity, a GM potato line (SGT 9-2) with reduced α-solanine content, and the parental control line (Desirée wild-type) having a traditional α-solanine: α-chaconine ratio were (1) studied for compositional similarity by analysing for a range of potato constituents, and (2) used in a 90-day feeding trial with the Syrian Golden hamster to study differential toxicity. The animal feeding study used diets with up to 60% freeze-dried potato powder from either line. Whilst data indicated some compositional differences between the GM line and its wildtype control these did not raise concerns related to nutritional value or safety. Results of the feeding trials showed a low number of significant differences between potato lines with different α-solanine: α-chaconine ratio but none were considered to raise safety concerns with regard to human (or animal) consumption.

Subtalar Arthrodesis Union Rates With and Without Adjacent Ankle Arthrodesis.

BACKGROUND: Subtalar arthrodesis is the surgical procedure commonly performed to treat subtalar arthritis. Subtalar arthrodesis may have a higher nonunion rate if there is a preexisting adjacent joint arthrodesis. The aim of this retrospective cohort study was to compare the subtalar arthrodesis union rate of patients with native tibiotalar joints to that of patients with prior tibiotalar arthrodesis. The secondary aim was to assess risk factors for nonunion. METHODS: A retrospective cohort study of consecutive patients that underwent a subtalar arthrodesis in a single center between 2010 and 2020. The primary outcome of union was determined based on bridging callus on radiographs and clinical symptoms. If there was uncertainty, then a nonweightbearing CT was acquired. Chi-squared test and Mann-Whitney tests compared differences in demographics and risk factors for nonunion between groups. A logistical regression model was performed to determine risk factors for nonunion. RESULTS: Eighteen patients had an adjacent ankle arthrodesis and 53 patients did not. The successful subtalar arthrodesis union rate in those with a preexisting ankle joint arthrodesis (44.4%) was approximately half that in those without an ankle joint arthrodesis (86.8%) (P < .001). On multivariate logistic regression, an adjacent ankle arthrodesis was the only significant risk factor for nonunion. The odds ratio of nonunion of the subtalar joint with an adjacent ankle arthrodesis present was 4.90 (95% CI 1.02-23.56) compared to a subtalar arthrodesis with a native ankle joint. In addition, 9.4% of patients without an ankle arthrodesis underwent a revision subtalar arthrodesis compared with 44.4% of those with an adjacent ankle arthrodesis (P = .001). CONCLUSION: In our study, we found that patients undergoing a subtalar arthrodesis with an adjacent ankle arthrodesis have a significantly increased risk of nonunion compared with those undergoing a subtalar arthrodesis with a native ankle. Patients with a previously fused ankle need counseling about the high risk of nonunion and potential additional surgery.

A new classification for Freiberg's disease.

INTRODUCTION: Freiberg's osteochondrosis is an uncommon cause of foot pain. Following a national survey circulated by the British Foot and Ankle Society it was found that no classification is used to guide surgical treatment. This study aimed to create a simple, reproducible CT based classification to preoperatively plan whether an osteotomy is required. METHODS: A retrospective review of 24 CT scans of new Freiberg's diseasediagnoses over a 10 year period was conducted. These images were assigned a study number and anonymised. The scans were then reviewed in their entirety by three independent specialists who determined whether an osteotomy would be of benefit. The sagittal CT slice that displayed the widest portion of proximal articular margin of the proximal phalanx was identified and divided the articular surface into 2 zones - plantar and dorsal and this formed the basis for our classification. These sagittal slices were then reviewed independently by two surgeons to determine if patients had disease in one or both zones and re-reviewed two weeks later to assess intra-observer reliability. RESULTS: All 24 cases involved the second metatarsal. From reviewing the sagittal CT slices, it was felt that 18 patients were suitable for osteotomy and 6 were suitable for debridement +/- arthroplasty alone. The current classification demonstrated that 18 patients had disease confined to zone 1 only and the remaining patients had disease in both zones. Inter-observer reliability assessment had 95.8% agreement (Krippendorff's Alpha 0.897). Intra-observer reliability was 100%. Correlation of those observed to have isolated zone 1 disease and suitability for osteotomy was absolute (Pearson r = 1). CONCLUSION: Dividing the metatarsal head into two zones on the widest sagittal slice of the CT scan offers an easy reproducible way to preoperatively plan surgical treatment for Freiberg's osteochondrosis. Patients with isolated zone 1 disease should be suitable for an osteotomy.

Metabolome variability in crop plant species--when, where, how much and so what?

"Omics" technologies provide coverage of gene, protein and metabolite analysis that is unsurpassed compared with traditional targeted approaches. There are a growing number of examples indicating that profiling approaches can be used to expose significant sources of variation in the composition of crop and model plants caused by genetic background, breeding method, growing environment (site, season), genotype × environment interactions and crop cultural practices to name but a few. Whilst breeders have long been aware of such variation from tried and tested targeted analytical approaches, the broad-scale, so called "unbiased" analysis of the metabolome now possible, offers a major upside to our understanding of the true extent of variation in a plethora of metabolites relevant to human and animal health and nutrition. Metabolomics is helping to provide targets for plant breeding by linking gene expression, and allelic variation to variation in metabolite complement (functional genomics), and is also being deployed to better assess the potential impacts of climate change and reduced input agricultural systems on crop composition. This review will provide examples of the factors driving variation in the metabolomes of crop species.

Successful performance of the bi-metric uncemented femoral stem at a minimum follow-up of 13 years in young patients.

We report the mean 15.2 year follow-up results for a porous coated version of the Bi-Metric (Biomet UK Ltd, Bridgend, UK) uncemented femoral stem in young patients. Sixty-four hips were implanted into 54 patients (mean age, 54.3 years) and followed up using the Hospital for Special Surgery score and regular radiographs. The first 13 patients had a TTAP-ST acetabulum (Biomet UK), the remainder receiving a Universal cup (Biomet UK). At 15.2 years, there were no stem failures or femoral revisions. The mean Hospital for Special Surgery score was 34.7 (20-40), and there was no evidence of stem loosening radiologically. There were 3 acetabular revisions and 3 liner changes at 10 years, with a further 5 cup revisions and 9 liner changes at final follow-up.

Comparison of Complication and Reoperation Rates for Minimally Invasive Versus Open Cheilectomy of the First Metatarsophalangeal Joint.

BACKGROUND: Dorsal cheilectomy of the first metatarsophalangeal joint is an accepted treatment to alleviate dorsal impingement, pain, and reduced dorsiflexion in hallux rigidus. Traditionally performed via an open incision, this procedure has more recently been performed using minimally invasive techniques despite limited supportive published evidence. METHODS: From December 2012 through December 2017, a retrospective analysis of all cheilectomies performed in our institution was done. The surgical technique was recorded along with any subsequent procedures performed for either persistent or recurrent pain, and complications were also noted. A comparison between open and minimally invasive outcomes was performed. In total, 171 cheilectomies were performed during this period. There were 38 open and 133 minimally invasive procedures. RESULTS: At a mean 3-year follow-up, the reoperation rates of the 2 groups were different with only 1 (2.6%) of the open group requiring a fusion, while 17 (12.8%) of the minimally invasive surgical (MIS) group required further surgery (relative risk, 4.86; P = .059). In the open group, there was 1 (2.6%) complication, compared with 15 (11.3%) in the minimally invasive group (relative risk, 4.29; P = .076). CONCLUSION: While patients may opt for MIS cheilectomy with a proposed faster recovery time and better cosmesis, they should be counseled about the risks and benefits of both methods, and that the technique of MIS cheilectomy utilized in this study appears to have an increased relative risk of requiring a further procedure. LEVEL OF EVIDENCE: Level III, retrospective comparative series.

The statistical relationship between varus deformity, surgeon's experience, BMI and tourniquet time for computer assisted total knee replacements.

The outcome of total knee arthroplasty (TKA) with severe pre-operative varus deformity is significantly worse than in well aligned knees. Computer navigated TKA has addressed some of the problems by ensuring accurate post-operative alignment. Our aims were to see if navigation could reproducibly correct a varus deformity to 3 degrees of the mechanical axis and to investigate the relationships between the tourniquet time and severity of the preoperative deformity, BMI and a surgeon's experience. The 172 e.motion floating platform TKA's were implanted using the OrthoPilot Navigation system (B Braun-Aesculap, Tuttlingen, Germany). Pre-operative deformity and post-operative alignment were measured by the software. Tourniquet times were recorded automatically. All knees were corrected to within 3 degrees of the neutral axis (mean 0.48 degrees ). Statistically significant relationships between tourniquet time (TT) and degree of pre-operative varus (p<0.001), total number of previous e.motion TKA's performed (p<0.001), and body mass index (p=0.013) were found. A linear relationship between the variables can be expressed as a statistical formula: TT=49.5+PreOp Varus+0.6(BMI)-0.1(total previous). Tourniquet time is measured in minutes and preoperative varus is measured in degrees from the mechanical axis. Total previous is the total number of navigated TKA's implanted by the surgeon. Tourniquet time is increased with larger pre-operative deformities and high BMI and decreased with surgical experience. The formula may give us a method of predicting the length of a procedure for a particular surgical team and may allow us to plan operating lists more accurately.

Fluid temperatures during arthroscopic subacromial decompression using a radiofrequency probe.

Our aim was to investigate the temperatures reached in the subacromial space during radiofrequency ablation of the subacromial bursa, in order to see if the probes generate sufficiently high temperatures to cause chondrolysis of the articular surfaces in the glenohumeral joint. We recorded the maximum temperatures in the subacromial space during arthroscopic subacromial decompression on 30 consecutive patients using a sterile digital temperature probe (Series 400, DeRoyal, TN, USA). Both the mean (27.8 degrees C) and maximum (41.8 degrees C) temperatures reached were below the experimental thresholds for chondrocyte damage. At 2 year follow-up we report no cases of chondrolysis or other complications related to the radiofrequency probes and conclude that given the relatively low maximum temperatures generated by the probes the risk of adverse effects is minimal.

The intragenic approach as a new extension to traditional plant breeding.

The novel intragenic approach to genetic engineering improves existing varieties by eliminating undesirable features and activating dormant traits. It transforms plants with native expression cassettes to fine-tune the activity and/or tissue specificity of target genes. Any intragenic modification of traits could, at least in theory, also be accomplished by traditional breeding and transgenic modification. However, the new approach is unique in avoiding the transfer of unknown or foreign DNA. By consequently eliminating various potential risk factors, this method represents a relatively safe approach to crop improvement. Therefore, we argue that intragenic crops should be cleared through the regulatory process in a timely and cost-effective manner.

Potato glycosterol rhamnosyltransferase, the terminal step in triose side-chain biosynthesis.

Steroidal glycoalkaloids (SGAs) are potentially harmful specialty metabolites found in Solanaceous plants. Two tri-glycosylated alkaloids, alpha-chaconine and alpha-solanine accumulate in potato tubers. Expressed sequence tags (ESTs) were identified in the available database by searching for protein homology to the Sgt1 (SOLtu:Sgt1) steriodalalkaloid galactosyltransferase. The EST sequence data was used to isolate Sgt3 cDNA sequences by polymerase chain reaction (PCR) from a wounded potato tuber cDNA library. The resulting 1515bp open reading frame of Sgt3, encodes a predicted SGT3 amino acid sequence that is 18 residues longer than, 45% identical to, and 58% homologous to the SGT1 protein. The amino-terminal region of the Sgt3 cDNA was used to create an antisense transgene under control of the granule bound starch synthase, GBSS6, promoter and the ubiquitin, Ubi3, polyadenylation signal. Analysis of SGA metabolites in selected transgenic tubers revealed a dramatic decrease in the accumulation of alpha-chaconine and alpha-solanine. This decrease was compensated by an increase in beta-solanine and beta-chaconine with minor accumulation of alpha-SGAs. These results allowed the identification of the function for SGT3 as the beta-solanine/beta-chaconine rhamnosyl transferase, the terminal step in formation of the potato glycoalkaloid triose side chains.

Competence-Based Curricula in the Context of Bologna and EU Higher Education Policy.

At the turn of the century European higher education policy became twin-track. The Bologna Process was launched and ran alongside developments in European legislation. Both tracks displayed a preoccupation with competences, in relation both to citizenship and to labour market needs. Scrutiny of important policy texts (Key Competences, the European Qualifications Framework, ECTS, the Bologna three-cycle degree structure) shows that 'competence' has never been given a precise and secure definition. Only very recently has the term entered the discourse of EU legislation on the recognition of professional qualifications. Current work on competence-based curricula in sectoral professions, including pharmacy, has helped bring the two policy tracks into closer alignment. The examples of competences identified in specific professional contexts can assist EU and Bologna policy-makers as they confront future challenges.