Gait kinematics and knee stability 10-years following posterior-stabilised total knee arthroplasty comparable to healthy adults >55.

PURPOSE: The purpose of this study was to compare the long-term objective biomechanical and functional parameters of a high-flexion total knee arthroplasty (TKA) design against healthy older adults to determine whether knee biomechanics are comparable in both populations. METHODS: One cohort of patients with a primary TKA, and a cohort of healthy adults over 55 years old with no musculoskeletal deficits or arthritis participated. Bilateral knee range of motion (RoM) was assessed with a goniometer, and gait patterns were analysed with a three-dimensional-motion capture system. An arthrometer quantified the anterior-posterior laxity of each knee. Statistical analyses were performed in SPSS software (α = 0.05). RESULTS: Twenty-three knees were replaced in 20 patients. At 9.8 ± 3.1 years postoperatively, patients' knees had a statistically significantly poorer RoM than healthy controls' knees (n = 23) due to limited flexion; p < 0.0001. Patients also failed to achieve the same degree of knee flexion as controls during downhill gait. No kinematic differences were observed during mid-flexion in level nor downhill gait; a state that has been associated with instability (p = 0.614; not significant [n.s]). There were no differences between groups in knee laxity (n.s). CONCLUSION: Patients in this study had similar gait patterns to healthy older adults during mid-flexion and were no more likely than the healthy controls to exhibit anterior-posterior translation of the knee > 7 mm; a known risk factor of instability. However, the knee flexion range was poorer. This likely led to bilateral pathological knee flexion patterns during downhill gait. LEVEL OF EVIDENCE: Level III.

The recombinant Link module of human TSG-6 suppresses cartilage damage in models of osteoarthritis: A potential disease-modifying OA drug.

OBJECTIVE: To investigate the role of endogenous TSG-6 in human osteoarthritis (OA) and assess the disease-modifying potential of a TSG-6-based biological treatment in cell, explant and animal models of OA. DESIGN: Knee articular cartilages from OA patients were analyzed for TSG-6 protein and mRNA expression using immunohistochemistry and RNAscope, respectively. The inhibitory activities of TSG-6 and its isolated Link module (Link_TSG6) on cytokine-induced degradation of OA cartilage explants were compared. Human mesenchymal stem/stromal cell-derived chondrocyte pellet cultures were used to determine the effects of Link_TSG6 and full-length TSG-6 on IL-1α-, IL-1ß-, or TNF-stimulated ADAMTS4, ADAMTS5, and MMP13 mRNA expression. Link_TSG6 was administered i.a. to the rat ACLTpMMx model; cartilage damage and tactile allodynia were assessed. RESULTS: TSG-6 is predominantly associated with chondrocytes in regions of cartilage damage where high TSG-6 expression aligns with low MMP13, the major collagenase implicated in OA progression. Link_TSG6 is more potent than full-length TSG-6 at inhibiting cytokine-mediated matrix breakdown in human OA cartilage explants;>50% of donor cartilages, from 59 tested, were responsive to Link_TSG6 treatment. Link_TSG6 also displayed more potent effects in 3D pellet cultures, suppressing ADAMTS4, ADAMTS5, and MMP13 gene expression, which was consistent with reduced aggrecanase and collagenase activities in explant cultures. Link_TSG6 treatment reduced touch-evoked pain behavior and dose-dependently inhibited cartilage damage in a rodent model of surgically-induced OA. CONCLUSIONS: Link_TSG6 has enhanced chondroprotective activity compared to the full-length TSG-6 protein and shows potential as a disease modifying OA drug via its inhibition of aggrecanase and collagenase activity.

Custom Implants in TKA Provide No Substantial Benefit in Terms of Outcome Scores, Reoperation Risk, or Mean Alignment: A Systematic Review.

BACKGROUND: Failure to accurately replicate the native anatomy and biomechanics of the knee has been suggested to contribute to dissatisfaction after TKA. Custom implants promise a personalized surgical approach, with the aim of improving patient satisfaction and pain as well as lowering revision rates. However, some published research on custom TKA implants has found no clinically important improvements in postoperative validated outcomes scores, risks of revision or reoperation, and implant alignment. In the interest of helping to settle this controversy, a systematic review seems warranted. QUESTION/PURPOSE: In this systematic review, we asked whether custom implants result in clinically important improvements over conventional off-the-shelf implants for anatomically uncomplicated primary TKA in terms of (1) validated outcomes scores, (2) the risk of revision or reoperation, and (3) implant alignment. METHODS: The US National Library of Medicine (PubMed/Medline), Embase, Web of Science, and Cochrane Database of Systematic Reviews were systematically searched to identify publications from the past 10 years relevant to this review. Publications that compared the clinical outcome measures, number of revisions and reoperations, and radiological assessment of implant alignment of custom and standard implants with validated endpoints were eligible for inclusion. In the interest of capturing as much potentially relevant information as possible, we applied no requirement for minimum follow-up duration. Clinical outcomes were assessed using patient-reported outcome (PROM) scores including the Knee Society Score (KSS), Forgotten Joint Score, and Knee Injury and Osteoarthritis Outcome Score. The risk for revision or reoperation were evaluated by the number of early and late manipulations, debridement procedures, and replacement of one or more components. Implant alignment was compared using postoperative deviation from the neutral (0°) mechanical axis of the limb and each component and the posterior tibial slope. All qualified studies were retrospective, and all compared custom implants with standard implants. Data on 1510 patients were reviewed (749 with custom implants and 761 with off-the-shelf implants). The mean follow-up time ranged from 12 to 33 months. RESULTS: There was no apparent advantage to custom implants in terms of PROM scores. Of the five studies evaluating clinical outcomes, only one reported better KSS-Function scores at 3 months; two reported no difference, and two found inferior KSS scores. In several studies, custom implants were associated with more frequent reoperations than standard implants. Although in general there were no differences between custom and standard implants in terms of mean coronal plane limb alignment, one of seven studies found that the proportion of patients whose alignment was outside ± 3° from the neutral axis in the coronal plane was lower in the custom group than in the standard group. CONCLUSION: With generally poorer outcomes scores for pain and function, generally higher risks of reoperation and reintervention, and no overall benefit to alignment, custom implants for primary TKA for the general population currently appear to be inferior to standard implants. Whether the slight reduction in the proportion of patients with alignment outliers observed in a minority of studies will result in a substantial reduction in revision risk over time must be addressed by future studies. However, until or unless such a reduction is proven, we recommend against the routine use of custom implants in practice because of increased costs and the risks associated with their novelty. LEVEL OF EVIDENCE: Level III, therapeutic study.

The First Report of the International Cartilage Regeneration and Joint Preservation Society's Global Registry.

OBJECTIVE: The International Cartilage Regeneration and Joint Preservation Society's (ICRS's) global registry, aims to be the best source of information for patients and an unbiased resource of evidence-based medicine for scientists and clinicians working to help those unfortunate enough to suffer the pain and disability associated with articular cartilage lesions. This article constitutes the scientific summary of the reports' main findings. DESIGN: The article outlines the historical precedents in the development of orthopedic registries from the earliest tumor registries, then local arthroplasty databases that led ultimately to international collaborations between national arthroplasty and soft tissue registries. The ICRS global cartilage registry was designed from the outset as a GDPR (General Data Protection Regulation) compliant, multilingual, multinational cooperative system. It is a web-based user-friendly, live in 11 languages by end 2019, which can be accessed via https://cartilage.org/society/icrs-patient-registry/. Patients and clinicians enter data by smartphone, tablet, or computer on any knee cartilage regeneration and joint preservation treatment, including the use of focal arthroplasty. Knee Injury and Osteoarthritis Outcome Score and Kujala patient-reported outcome measures are collected preoperatively, 6 months, 12 months, and annually for ten years thereafter. EQ-5D data collection will allow cost-effectiveness analysis. Strengths, weaknesses, and future plans are discussed. RESULTS: Since inception the registry has 264 users across 50 countries. Major findings are presented and discussed, while the entire first ICRS global registry report is available at https://cartilage.org/society/icrs-patient-registry/registry-annual-reports/. Conclusion. A measure of the maturity of any registry is the publication of its findings in the peer reviewed literature. With the publication of its first report, the ICRS global registry has achieved that milestone.

Clinically Relevant Molecular Biomarkers for Use in Human Knee Osteoarthritis: A Systematic Review.

OBJECTIVE: Biomarkers in osteoarthritis (OA) could serve as objective clinical indicators for various disease parameters, and act as surrogate endpoints in clinical trials for disease-modifying drugs. The aim of this systematic review was to produce a comprehensive list of candidate molecular biomarkers for knee OA after the 2013 ESCEO review and discern whether any have been studied in sufficient detail for use in clinical settings. DESIGN: MEDLINE and Embase databases were searched between August 2013 and May 2018 using the keywords "knee osteoarthritis," "osteoarthritis," and "biomarker." Studies were screened by title, abstract, and full text. Human studies on knee OA that were published in the English language were included. Excluded were studies on genetic/imaging/cellular markers, studies on participants with secondary OA, and publications that were review/abstract-only. Study quality and bias were assessed. Statistically significant data regarding the relationship between a biomarker and a disease parameter were extracted. RESULTS: A total of 80 studies were included in the final review and 89 statistically significant individual molecular biomarkers were identified. C-telopeptide of type II collagen (CTXII) was shown to predict progression of knee OA in urine and serum in multiple studies. Synovial fluid vascular endothelial growth factor concentration was reported by 2 studies to be predictive of knee OA progression. CONCLUSION: Despite the clear need for biomarkers of OA, the lack of coordination in current research has led to incompatible results. As such, there is yet to be a suitable biomarker to be used in a clinical setting.

A Randomized Controlled Trial Comparing Traditional Plaster Cast Rehabilitation With Functional Walking Boot Rehabilitation for Acute Achilles Tendon Ruptures.

BACKGROUND: There has been a shift toward functional nonoperative rehabilitation in the treatment of Achilles tendon rupture (ATR) despite a shortage of studies directly comparing nonoperative functional rehabilitation with traditional nonoperative immobilization. PURPOSE: To compare patient-reported outcome measures and functional outcomes for nonoperatively treated ATR with traditional cast immobilization or functional rehabilitation in a walking boot. STUDY DESIGN: Randomized controlled clinical trial; Level of evidence, 2. METHODS: In a single-center nonblinded study, 140 patients were randomized to compare treatment for acute ATR in (1) an immobilizing cast in reducing degrees of equinus over a 10-week period with 8 weeks of nonweightbearing mobilization or (2) a walking boot for 8 weeks with reducing equinus and immediate full weightbearing. Exclusion criteria were delayed presentation >2 weeks after injury, tendon reruptures, and latex allergy. Analysis was undertaken on an intention-to-treat basis. RESULTS: A total of 69 patients (median age, 41 years [interquartile range, 33-50.5 years]) were randomized to walking boot treatment and 71 patients (41 [32-49]) to cast treatment. At 6 months, patients treated in a walking boot reported better Short Musculoskeletal Function Assessment (SMFA) dysfunction index (6.62 [2.21-12.50] vs 10.66 [4.96-13.42]; P = .050), SMFA bother index (7.29 [2.08-14.58] vs 10.42 [5.73-19.27]; P = .04), Achilles Tendon Total Rupture Score (71.5 [53.50-84.25] vs 54.0 [37-76]; P = .01), and Foot and Ankle Questionnaire core score (91 [81.89-97.55] vs 85 [78.25-92.09]; P = .04). At 1 year, there was no difference in SMFA dysfunction index (2.21 [0.74-5.88] vs 2.94 [1.47-6.62]; P = .25), SMFA bother index (2.08 [0-9.38] vs 5.21 [0.52-11.98]; P = .25), Achilles Tendon Total Rupture Score (92 [72.50-96] vs 87.5 [66.0-94.75]; P = .21), or Foot and Ankle Questionnaire core score (97.75 [89.46-99.00] vs 95.50 [90.88-97.50]; P = .18). Rerupture occurred in 5 and 11 patients (P = .075) and venous thromboembolism in 2 and 3 patients (P = .67) in the boot and cast groups, respectively. Fifteen patients in the boot group but none in the cast group had skin problems (P < .001). Patients treated in a boot returned to driving at a median 12 weeks (vs 13 weeks for cast; P = .045), but there was no difference in time to return to work (P = .48). CONCLUSION: Functional rehabilitation with early weightbearing is a safe alternative to traditional immobilizing treatment for ATR, giving better early functional outcomes, albeit with a higher incidence of transient minor skin complications. REGISTRATION: NCT02598843 (ClinicalTrials.gov identifier).

Undertriage of the elderly major trauma patient continues in major trauma centre care: a retrospective cohort review.

BACKGROUND: Major trauma (Injury Severity Score (ISS) ≥16) in older people is increasing, but concerns persist that major trauma is not always recognised in older patients on triage. This study compared undertriage of older and younger adult major trauma patients in the major trauma centre (MTC) setting to investigate this concern. METHODS: A retrospective review of Trauma Audit and Research Network data was conducted for three MTCs in the UK for 3 months in 2014. Age, ISS, injury mechanism and injured areas were examined for all severely injured patients (ISS ≥16) and appropriate major trauma triage rates measured via the surrogate markers of trauma team activation and the presence of a consultant first attender, as per standards for major trauma care set by National Confidential Enquiry into Patient Outcomes and Deaths, Royal College of Surgeons of England and the British Orthopaedic Association. Trends in older (age ≥65) and younger (ages 18-64) adult major trauma presentation, triage and reception were reviewed. RESULTS: Of 153 severely injured patients, 46 were aged ≥65. Older patients were significantly less likely to receive the attention of a consultant first attender or trauma team. Similar trends were also seen on subgroup analysis by mechanism of injury or number of injured body areas. Older major trauma patients exhibit a higher mortality, despite a lower median ISS (older patient ISS=20 (IQR 16-25), younger patient ISS=25 (IQR 18-29)). CONCLUSION: Older major trauma patients are at greater risk of undertriage, even in the MTC environment. Existing hospital trauma triage practices should be further investigated to explain and reduce undertriage of elderly trauma patients.

Health costs and efficiencies of patient-specific and single-use instrumentation in total knee arthroplasty: a randomised controlled trial.

Aim: To investigate whether patient-specific instrumentation (PSI) and single-use instrumentation (SUI) improve operating room efficiency in terms of time and cost to the healthcare provider over conventional/reusable instrumentation (CVR) when performing total knee arthroplasty (TKA). Patients and methods: Patients requiring TKA were randomised into one of four surgical groups: CVR, CVS (conventional/SUI), PSR (PSI/reusable) and PSS (PSI/SUI). All surgical procedures were video recorded to determine specific surgical time intervals. Other variables reported included the number of instrument trays used, missing equipment, direct instrument costs and the weight of the instruments the staff had to handle. Oxford Knee Score (OKS), estimated blood loss and lengths of hospital stay were also recorded as markers of patient experience. Results: PSR was significantly quicker in all the recorded time intervals, used less trays, experienced less missing equipment and resulted in lower blood loss and shorter hospital stays. SUI reported significantly slower operating room times and resulted in higher blood loss, but SUI was 88% lighter and 20% cheaper on average when compared with their reusable counterparts. Despite the economic advantages of PSI and SUI, the patients who reported greatest improvements in OKS were those allocated to the CVR group, but no clinically meaningful difference in OKS was found at any time point. Conclusions: PSI and SUI for TKA have the potential of reducing operating room times over conventional, reusable sets. This reduction will benefit theatre personnel ergonomically, while presenting the healthcare provider with potential cost-saving benefits in terms of reduced sterilisation costs and surgical times.

Effect of Alendronic Acid on Fracture Healing: A Multicenter Randomized Placebo-Controlled Trial.

There is a concern that bisphosphonates may impair fracture healing because of their inhibitory effects on bone turnover. Here we evaluated the effects of early bisphosphonate therapy on fracture healing and functional outcome following a fracture of the distal radius. The fracture and bisphosphonates (FAB) trial was a double-blind, randomized, placebo-controlled trial involving 15 trauma centers in the United Kingdom. We enrolled 421 bisphosphonate-naive patients aged ≥50 years with a radiographically confirmed fracture of the distal radius and randomized them in a 1:1 ratio to receive alendronic acid 70 mg once weekly (n = 215) or placebo (n = 206) within 14 days of the fracture. The primary outcome measure was the proportion of fractures that had radiologically united at 4 weeks as assessed by an observer, blinded to treatment allocation. Secondary outcomes included the Disabilities of the Arm Shoulder and Hand (DASH) questionnaire, range of wrist movement and grip strength, pain and analgesia requirements, and the rate of malunion. The mean ± SD age of participants was 63 ± 8.5 years and 362 (86%) were female. At 4 weeks, 48 of 202 (23.8%) fractures had united in the alendronic acid group compared with 52 of 187 (27.8%) in the placebo group (observed absolute proportion difference 4.0%; 95% CI, -4.7% to 12.8%; p = 0.36). The absolute proportion difference between groups based on imputed data was 4.5% (95% CI, -4.7% to 13.8%; p = 0.30). There was no significant difference in the proportion of fractures that had united at any other time point and no differences in the DASH score, pain at the fracture site, grip strength, or any other clinical outcome. We conclude that among patients aged 50 years and above with a distal radius fracture, early administration of alendronic acid does not adversely affect fracture union or clinical outcome. These findings suggest bisphosphonate therapy can be safely commenced early after fracture if clinically indicated. © 2019 American Society for Bone and Mineral Research.

Autologous chondrocyte implantation in the knee: systematic review and economic evaluation.

BACKGROUND: The surfaces of the bones in the knee are covered with articular cartilage, a rubber-like substance that is very smooth, allowing frictionless movement in the joint and acting as a shock absorber. The cells that form the cartilage are called chondrocytes. Natural cartilage is called hyaline cartilage. Articular cartilage has very little capacity for self-repair, so damage may be permanent. Various methods have been used to try to repair cartilage. Autologous chondrocyte implantation (ACI) involves laboratory culture of cartilage-producing cells from the knee and then implanting them into the chondral defect. OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of ACI in chondral defects in the knee, compared with microfracture (MF). DATA SOURCES: A broad search was done in MEDLINE, EMBASE, The Cochrane Library, NHS Economic Evaluation Database and Web of Science, for studies published since the last Health Technology Assessment review. REVIEW METHODS: Systematic review of recent reviews, trials, long-term observational studies and economic evaluations of the use of ACI and MF for repairing symptomatic articular cartilage defects of the knee. A new economic model was constructed. Submissions from two manufacturers and the ACTIVE (Autologous Chondrocyte Transplantation/Implantation Versus Existing Treatment) trial group were reviewed. Survival analysis was based on long-term observational studies. RESULTS: Four randomised controlled trials (RCTs) published since the last appraisal provided evidence on the efficacy of ACI. The SUMMIT (Superiority of Matrix-induced autologous chondrocyte implant versus Microfracture for Treatment of symptomatic articular cartilage defects) trial compared matrix-applied chondrocyte implantation (MACI®) against MF. The TIG/ACT/01/2000 (TIG/ACT) trial compared ACI with characterised chondrocytes against MF. The ACTIVE trial compared several forms of ACI against standard treatments, mainly MF. In the SUMMIT trial, improvements in knee injury and osteoarthritis outcome scores (KOOSs), and the proportion of responders, were greater in the MACI group than in the MF group. In the TIG/ACT trial there was improvement in the KOOS at 60 months, but no difference between ACI and MF overall. Patients with onset of symptoms < 3 years' duration did better with ACI. Results from ACTIVE have not yet been published. Survival analysis suggests that long-term results are better with ACI than with MF. Economic modelling suggested that ACI was cost-effective compared with MF across a range of scenarios. LIMITATIONS: The main limitation is the lack of RCT data beyond 5 years of follow-up. A second is that the techniques of ACI are evolving, so long-term data come from trials using forms of ACI that are now superseded. In the modelling, we therefore assumed that durability of cartilage repair as seen in studies of older forms of ACI could be applied in modelling of newer forms. A third is that the high list prices of chondrocytes are reduced by confidential discounting. The main research needs are for longer-term follow-up and for trials of the next generation of ACI. CONCLUSIONS: The evidence base for ACI has improved since the last appraisal by the National Institute for Health and Care Excellence. In most analyses, the incremental cost-effectiveness ratios for ACI compared with MF appear to be within a range usually considered acceptable. Research is needed into long-term results of new forms of ACI. STUDY REGISTRATION: This study is registered as PROSPERO CRD42014013083. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Cell Viability in Arthroscopic Versus Open Autologous Chondrocyte Implantation.

BACKGROUND: Autologous chondrocyte implantation (ACI) is an effective method of repair of articular cartilage defects. It is a 2-stage operation, with the second stage most commonly performed via mini-arthrotomy. Arthroscopic ACI is gaining popularity, as it is less invasive and may accelerate early rehabilitation. However, handling and manipulation of the implant have been shown to cause chondrocyte cell death. PURPOSE: To assess the number and viability of cells delivered via an open versus arthroscopic approach in ACI surgery. STUDY DESIGN: Controlled laboratory study. METHODS: Sixteen ACI surgeries were performed on young cadaveric knees by 2 experienced surgeons: 8 via mini-arthrotomy and 8 arthroscopically. Live and dead cells were stained and counted on implants after surgery. The cell number and viability were assessed using confocal laser scanning microscopy. Surgery was timed from knife to skin until the end of cycling the knee 10 times after implantation of the cell-membrane construct. RESULTS: On receipt of cell membranes after transportation from the laboratory, ≥92% of the cells were viable. There were significantly more remaining cells (8.47E+07 arthroscopic vs 1.41E+08 open; P < .001) and 16 times more viable cells (3.62% arthroscopic vs 37.34% open; P < .001) on the implants when they were inserted via mini-open surgery compared with the arthroscopic technique. Open surgery was of a significantly shorter duration (6 vs 32 minutes; P < .001). CONCLUSION: In this study, there were significantly more viable cells on the implant when ACI was performed via mini-arthrotomy compared with an arthroscopic technique. CLINICAL RELEVANCE: The viability of cells delivered for ACI via an arthroscopic approach was 16 times less than via an open approach. The mini-arthrotomy approach is recommended until long-term clinical comparative data are available.

Perivascular Mesenchymal Stem Cells in Sheep: Characterization and Autologous Transplantation in a Model of Articular Cartilage Repair.

Previous research has indicated that purified perivascular stem cells (PSCs) have increased chondrogenic potential compared to conventional mesenchymal stem cells (MSCs) derived in culture. This study aimed to develop an autologous large animal model for PSC transplantation and to specifically determine if implanted cells are retained in articular cartilage defects. Immunohistochemistry and fluorescence-activated cell sorting were used to ascertain the reactivity of anti-human and anti-ovine antibodies, which were combined and used to identify and isolate pericytes (CD34-CD45-CD146+) and adventitial cells (CD34+CD45-CD146-). The purified cells demonstrated osteogenic, adipogenic, and chondrogenic potential in culture. Autologous ovine PSCs (oPSCs) were isolated, cultured, and efficiently transfected using a green fluorescence protein (GFP) encoding lentivirus. The cells were implanted into articular cartilage defects on the medial femoral condyle using hydrogel and collagen membranes. Four weeks following implantation, the condyle was explanted and confocal laser scanning microscopy demonstrated the presence of oPSCs in the defect repaired with the hydrogel. These data suggest the testability in a large animal of native MSC autologous grafting, thus avoiding possible biases associated with xenotransplantation. Such a setting will be used in priority for indications in orthopedics, at first to model articular cartilage repair.

Retrieval analysis of a failed TriboFit polycarbonate urethane acetabular buffer.

The purpose of this research was to determine the failure mechanisms and damage features of a TriboFit acetabular buffer implanted directly against a native, prepared acetabulum which was revised after 11months. Retrieval analyses were carried out via light microscopy, gravimetric wear assessment, and observer scoring of visible damage features on the buffer. The volume of material abraded from the backside of the buffer was estimated via three-dimensional reconstruction using a laser scanner. Scanning electron microscopy was used to confirm damage features and mechanisms. Severe abrasion to the backside of the buffer was the primary damage feature, while stippling damage was seen on the articular surface of the buffer. Material loss due to backside abrasion was approximated to be between 0.13360.085 g (gravimetric analyses) and 0.19360.053 g (three-dimensional reconstruction). Implantation of the TriboFit buffer against the patient's native acetabulum without a metal backing allowed for significant movement of the buffer against the bone, resulting in the abrasion seen on this implant. The stippling damage on the articular surface indicates an adhesive wear mechanism which exacerbates movement of the buffer against the acetabulum, thereby increasing backside abrasion.

A Systematic Review of the Role of Vitamin D on Neuromuscular Remodelling Following Exercise and Injury.

UNLABELLED: Vitamin D is important for skeletal muscle health and deficiency is associated with clinical neuromuscular symptoms of poor strength and gait. Supplementation can independently increase muscle strength in chronically deficient populations. However, the regulatory role of vitamin D on neuromuscular remodelling and adaptation subsequent to exercise conditioning or injury has not been systematically reviewed. OBJECTIVE: to systematically review the available evidence of the role of vitamin D on neuromuscular remodelling following exercise conditioning, exercise- or experimentally induced injury. We searched Medline (OVID platform), PubMed, Embase and Web of Science for randomised controlled trials (RCTs) including measures of neuromuscular function, injury and/or inflammation; a physiologically stressful intervention involving exercise conditioning, exercise- or experimentally induced injury and; vitamin D supplementation. Nine RCTs met the inclusion criteria. Significant heterogeneity of methodological approaches and outcomes meant that meta-analysis of data was limited. Qualitative findings indicated that vitamin D may be an effective accelerant of neuromuscular remodelling in animal models (24-140 % improved recovery vs. control); the effects in humans are inconclusive and likely influenced by baseline vitamin D and supplementation strategy. Results of the meta-analyses indicated no effect of vitamin D supplementation on muscle strength adaptation following resistance training [standardised mean difference (SMD): 0.74, P = 0.42] or muscle damage (SMD: -0.03, P = 0.92), although inflammatory markers were elevated in the latter (SMD: 0.56, P = 0.04). Data from animal models offer promising and plausible mechanisms for vitamin D as an agent for neuromuscular adaptation. Further high-quality research is needed to offer clearer insight into the influential role of vitamin D in human populations.

The surgical management of symptomatic articular cartilage defects of the knee: Consensus statements from United Kingdom knee surgeons.

BACKGROUND: Symptomatic articular cartilage and osteochondral lesions in the knee are an important source of pain and disability, and may lead to osteoarthritis. There are several surgical treatments for the condition, with emerging data evaluating their clinical effectiveness and longer-term clinical outcome. Health care providers have challenged the indications for the use of expensive techniques and have been reluctant to authorize funding or reimbursement. METHODS: The UK Cartilage Consensus Meeting was convened, involving clinicians in the UK with experience in the treatment options, decision-making and evaluation of the literature on the subject. RESULTS: This paper reports the consensus of attendees regarding appropriate surgical options for managing articular cartilage defects in the knee, validated by a large cohort of surgeons in the UK who are active in the field of articular cartilage surgery. CONCLUSIONS: An evidence-based United Kingdom Consensus of 104 clinicians on the surgical management of symptomatic articular cartilage lesions of the knee. Several techniques may be suitable for small defects. Cell therapy has the best evidence-based outcomes for larger defects. Responsible innovation, pooled data collection and improvement in physical therapies are important. Surgeons should have access to the most appropriate evidence-based therapies for first-line treatment.

Variations In Good Patient Reported Outcomes After Total Knee Arthroplasty.

This study identifies optimal OKS values that discriminate post-operative (TKA) patient satisfaction and determines the variation in threshold values by patient characteristics and expectations. It is the first to identify patient improvement using measures (PoPC) that account for patient's pre-operative symptom severity. Of 365 primary TKA patients from a London district general hospital 84% were satisfied at 12 and 24 months. Whilst the overall OKS thresholds (follow-up, change, PoPC) were stable at 12 months (31, 11, 39.7%) and 24 months (35, 12, 38.9%), patients who were older (≥75years), were underweight/normal (BMI<25), had pre-operative symptom severity (OKS≤15) and expected no pain post-surgery, required a greater (potential) improvement to be classed as satisfied. When reporting good patient outcomes, cohorts should be stratified accordingly.

Viability of chondrocytes seeded onto a collagen I/III membrane for matrix-induced autologous chondrocyte implantation.

Cell viability is crucial for effective cell-based cartilage repair. The aim of this study was to determine the effect of handling the membrane during matrix-induced autologous chondrocyte implantation surgery on the viability of implanted chondrocytes. Images were acquired under five conditions: (i) Pre-operative; (ii) Handled during surgery; (iii) Cut edge; (iv) Thumb pressure applied; (v) Heavily grasped with forceps. Live and dead cell stains were used. Images were obtained for cell counting and morphology. Mean cell density was 6.60 × 10(5) cells/cm(2) (5.74-7.11 × 10(5) ) in specimens that did not have significant trauma decreasing significantly in specimens that had been grasped with forceps (p < 0.001) or cut (p = 0.004). Cell viability on delivery grade membrane was 75.1%(72.4-77.8%). This dropped to 67.4%(64.1-69.7%) after handling (p = 0.002), 56.3%(51.5-61.6%) after being thumbed (p < 0.001) and 28.8%(24.7-31.2%) after crushing with forceps (p < 0.001). When cut with scissors there was a band of cell death approximately 275 µm in width where cell viability decreased to 13.7%(10.2-18.2%, p < 0.001). Higher magnification revealed cells without the typical rounded appearance of chondrocytes. We found that confocal laser-scanning microscope (CLSM) can be used to quantify and image the fine morphology of cells on a matrix-induced autologous chondrocyte implantation (MACI) membrane. Careful handling of the membrane is essential to minimise chondrocyte death during surgery.

Long-term results of autologous chondrocyte implantation in the knee for chronic chondral and osteochondral defects.

BACKGROUND: Autologous chondrocyte implantation (ACI) has been shown to be effective in the midterm for the treatment of symptomatic articular cartilage lesions of the knee, but few long-term series have been published. The multioperated chronic articular cartilage defect remains a difficult condition to treat. PURPOSE: To examine the long-term clinical results of ACI for large chronic articular cartilage defects, many treated as salvage. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: This is a prospective case series of 104 patients with a mean age of 30.2 years and a symptomatic lesion of the articular cartilage in the knee, who underwent ACI between 1998 and 2001. The mean duration of symptoms before surgery was 7.8 years. The mean number of previous surgical procedures on the cartilage defect, excluding arthroscopic debridement, was 1.3. The defects were large, with a mean size of 477.1 mm(2) (range, 120-2500 mm(2)). The modified Cincinnati, Stanmore/Bentley, and visual analog scale for pain scoring systems were used to assess pain and functional outcomes at a minimum 10 years (mean, 10.4 years; range, 10-12 years). RESULTS: Twenty-seven patients (26%) experienced graft failure at a mean of 5.7 years after ACI. Of the 73 patients who did not fail, 46 patients (63% of patients with a surviving graft) had an excellent result, 18 (25%) were good, 6 (8%) were fair, and 3 (4%) had a poor result. Of a total of 100 patients successfully followed up, 98 were satisfied with the ACI technique for their chronic knee pain and would undergo the procedure again. CONCLUSION: Autologous chondrocyte implantation can provide a long-term solution in more than 70% of young patients of a difficult-to-treat group with large chronic articular cartilage lesions, even in the salvage situation.