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.
To assess the clinical effectiveness and cost-effectiveness of ACI in chondral defects in the knee, compared with microfracture (MF).
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.
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.
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.
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.
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.
This study is registered as PROSPERO CRD42014013083.
The National Institute for Health Research Health Technology Assessment programme.
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.
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.
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)).
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.
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.
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.
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.
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.
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.
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 III, therapeutic study.
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 mm2 (range, 120-2500 mm2). 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.
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.
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.
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