Abstract. Introduction. Skeletal muscle wasting is an important clinical issue following acute traumatic injury, and can delay recovery and cause permanent functional disability particularly in the elderly. However, the fundamental mechanisms involved in trauma-induced muscle wasting remain poorly defined and therapeutic interventions are limited. Objectives. To characterise local and systemic mediators of skeletal muscle wasting in elderly patients following acute trauma. Methods. Experiments were approved by a local NHS Research Ethics Committee and all participants provided written informed consent. Vastus lateralis biopsies and serum samples were taken from human male and female patients shortly after acute trauma injury in lower limbs (n=6; mean age 78.7±4.4 y) and compared to age-matched controls (n=6; mean age 72.6±6.3 y). Atrogenes and upstream regulators (MuRF1; MAFbx; IL6, TNFα, PGC-1α) mRNA expression was assessed in muscle samples via RT-qPCR. Serum profiling of inflammatory markers (e.g. IL6, TNFα, IL1β) was further performed via multiplex assays. To determine whether systemic factors induced by trauma directly affect muscle phenotype, differentiated primary human myotubes were treated in vitro with serum from controls or trauma patients (pooled; n=3 each) in the final 24 hours of differentiation. Cells were then fixed, stained for myogenin and imaged to determine minimum ferret diameter. Statistical significance was determined at P<0.05. Results. There was an increase in skeletal muscle mRNA expression for E3 ligase MAFbx and inflammatory cytokine IL-6 (4.6 and 21.5-fold respectively; P<0.05) in trauma patients compared to controls. Expression of myogenic determination factor MyoD and regulator of mitochondrial biogenesis PGC-1α was lower in
In a decidedly upper limb themed series of reviews this edition of Cochrane Corner summarises four new and updated reviews published by the Cochrane Bone, Joint and
Objectives. To investigate the value of tranexamic acid (TA) in reducing blood loss and blood transfusion after TKR and other clinical outcomes such as deep venous thrombosis (DVT), pulmonary embolism (PE), ischaemic heart diseases and mortality. Methods. A systematic review and meta-analysis of published randomised and quasi-randomised trials which used TA to reduce blood loss in knee arthroplasty was conducted. The data was evaluated using the generic evaluation tool designed by the Cochrane Bone, Joint and
Aim. This study aims to determine the value of MRI in children with hip pain which remained unexplained following routine investigations including ultrasound examination. Materials and methods. Retrospective review of clinical notes and MRI findings in all children who received and MRI scan for undiagnosed hip pain over three years. Results. Fifty five children underwent an MRI scan of their hips for unexplained hip pain. 29 were male and 26 were female. The mean age was 10.9 years. The MR study provided a diagnosis in 22 children (40%), and was normal in 33 children (60%). Five cases were considered to be due to transient synovitis. Three children were diagnosed as osteoid osteoma. Two children were were found to have trochanteric bursitis. Two children were shown to have
Various reports confirm that elevations in serum markers associated with skeletal muscle injury exist and can occur after orthopaedic surgery in the absence of overt clinical manifestations of myocardial injury. The purpose of this study is to measure the influence surgical approach on these serum markers following primary Minimally Invasive THA. Consecutive enrollment of 30 patients into three different groups of 10 was performed. The MIS Modified Watson Jones THA is an approach using an inter-muscular plane, the Mini Posterior is a trans-muscular approach with some muscle detachment and repair, while the MIS II Incision THA is an inter-muscular approach anteriorly and a trans-muscular approach posteriorly. Blood samples for total creatine kinase (CK), creatine phospho-kinase (CPK), and serum myoglobin were obtained at screening and the morning before surgery as a baseline, immediately post-operatively in the recovery room and 8, 16, 24, 36, 48, and 72 hours post-operatively. Hemoglobin and hematocrit was obtained pre-operatively, 16, 36, and 72 hours (±6 hours) post-operatively. Cardiac troponin-I was measured the morning before surgery (pre-operatively) and 16 hours following surgery to monitor any contributory effect of myocardial injury. We report measurable and reproducible trends in serum enzyme levels consistent with skeletal muscle damage due to THA. Troponin-I remained normal in all but one case throughout the entire study indicating no myocardial contribution to measured serum enzyme levels. While these trends may have slight correlation with surgical approach, they were not statistically significant. We conclude that all three procedures do affect serum enzyme markers and are safe from this standpoint, but no surgical approach appears to affect the degree of
Background and aim. Total hip replacements (THRs) are associated with significant blood loss which often requires high transfusion rates of allogeneic blood. Although safer than ever, allogeneic blood transfusion is still associated with risks to the recipients. This meta-analysis aims to investigate the efficacy and safety of tranexamic acid (TXA) in reducing blood loss and allogeneic blood transfusion after THR. Patients and Methods. A systematic review and meta-analysis of published randomised controlled trials which used TXA to reduce blood loss and transfusion in hip arthroplasty were conducted. The data were evaluated using the generic evaluation tool designed by the Cochrane Bone, Joint and
There is evidence that morbidly obese patients have more intra- and postoperative complications and poorer outcomes when undergoing total hip arthroplasty (THA) with the direct anterior approach (DAA). The aim of this study was to determine the efficacy of DAA for THA, and compare the complications and outcomes of morbidly obese patients with nonobese patients. Morbidly obese patients (n = 86), with BMI ≥ 40 kg/m2 who underwent DAA THA at our institution between September 2010 and December 2017, were matched to 172 patients with BMI < 30 kg/m2. Data regarding demographics, set-up and operating time, blood loss, radiological assessment, Harris Hip Score (HHS), International Hip Outcome Tool (12-items), reoperation rate, and complications at two years postoperatively were retrospectively analyzed.Aims
Methods
Background: Total hip replacement (THR) is one of the commonest operations in orthopaedic practice. Literature review showed that 20–70% of patients who underwent THR needed 1–3 units of blood. Although safer than ever, allogeneic transfusion is still associated with risks for the recipient. There has been unsettled search for ways to reduce such blood loss and transfusion. Tranexamic acid has been popularised as an effective way to reduce blood loss and subsequent blood transfusion. Objectives: To investigate the value of Tranexamic acid in reducing blood loss and blood transfusion after THR and other clinical outcomes such as deep venous thrombosis (DVT), pulmonary embolism (PE), ischaemic heart diseases and mortality. Patients and Methods: A systematic review and meta-analysis of published randomised and quasi-randomised trials which used tranexamic acid to reduce blood loss in hip arthroplasty was conducted. The data was evaluated using the generic evaluation tool designed by the Cochrane Bone, Joint and
Pulsed Electromagnetic Fields (PEMFs) promote joint tissue anabolic activities, particularly in cartilage and bone. Here we investigated the effect of selected PEMFs (75Hz, 1.5mT, 1.3msec) in a differentiating model of murine myoblasts (C2C12) in vitro. C2C12 were seeded at 5×10. 3. cells/cm. 2. in 4 well plates and left to adhere for 24h. Subsequently, cells were either maintained in growth medium (GM) or induced towards myogenic differentiation in low-serum conditions, with and without PEMF exposure, for 4 days. Morphological analysis, myotube formation and fusion index (FI) were assessed with fluorescence microscopy techniques. Metabolic activity was determined by MTT; moreover, a multiplex cytokine array (RayBiotech) allowed cell supernatant molecule quantification. Cells exposed to PEMFs in GM acquired a distinctive elongated morphology, with increased bi-nuclear figures (3.2-fold FI increase over PEMF-unexposed cells) and displayed a significantly higher metabolic activity (+31%, p<0.05 over PEMF-unexposed cells). PEMF exposure increased metabolic activity also under myogenic differentiation (+15% over PEMF-unexposed differentiating cells, p<0.05), with the formation of long, thick polynuclear myotubes, suggesting a role of PEMFs in enhancing myogenesis (7.7-fold FI increase over PEMF-unexposed cells). 4-day culture supernatants revealed the presence of several myokines (KC/CXCL1, LIX, MCP-1, TIMP-1). Preliminary analysis showed a 1.16-fold increase (n=2) of LIX and, notably, a 1.91-fold increase (n=2) of TNF-RI, in cell supernatants of PEMF-exposed over PEMF-unexposed cells. Collectively, these results suggest that PEMF may successfully be applied in models of
It has been suggested that smaller skin incisions may be associated with a better short-term outcome after total hip replacement, including a more rapid rehabilitation. The definition of mini-incision is still unclear as publications with incisions ranging from five to 20 cms appear in the literature. We therefore prospectively studied 42 consecutive patients who had undergone 44 total hip replacements using a posterolateral approach, through skin incisions of between 10 and 21 cm. The patients were assessed for their speed of post-operative rehabilitation and their length of hospital stay. Age, body mass index, length of incision, duration of procedure, muscles detached and repaired, and blood loss were also recorded. We found no evidence of a correlation between incision size and blood loss, post-operative rehabilitation, or the length of hospital stay. Similarly, the degree of surgical
Background: Traditionally, non-displaced scaphoid fractures are considered by most as stable with predictable rates of healing with conservative treatment. There is a current trend in orthopedic practice, however, to treat non- or minimal displaced fractures with early open reduction and internal fixation. This trend is not evidence based. In this systematic review and meta-analysis, we pool data from trials comparing surgical and conservative treatment for acute scaphoid fractures, thus aiming to summarize the best available evidence. Methods: We searched the Cochrane Bone, Joint and
Introduction. Osteochondral defects of the talus are usually a consequence of trauma. They can cause chronic pain and serious disability. Various interventions, non-surgical and surgical, have been used for treating these defects. The objective of this Cochrane systematic review of randomised control trials is to determine the benefits and harms of the interventions used for treating osteochondral defects of the talus in adults. Methods. We searched the Cochrane Bone, Joint and
Background: Scientific investigation of
Objectives: To compare the results of various surgical approaches to the knee in primary arthroplasty surgery. Design: Systematic review with meta-analysis. Data Sources: Cochrane Bone, Joint, and
Introduction: Minimally invasive total hip arthroplasty has evoked substantial controversy with regard to whether it provides superior outcomes compared with conventional total hip arthroplasty. The objective of this study was to compare the results of a minimal invasive direct anterior approach (MIDA) with those of a conventional lateral transgluteal approach (CLT). Methods: 120 patients (120 hips) admitted for unilateral total hip arthroplasty were randomized to undergo surgery via minimal invasive direct anterior or conventional lateral transgluteal approach. Patients with a body mass index of more than 35, previous hip surgery, preoperative neurological deficits and with an age of more than 80 years were excluded. Two surgeons performed all procedures. To estimate muscle damage serum creatinkinase was assessed. Blood loss was calculated according to Rosencher by comparing preoperative to postoperative hematocrit. Postoperative pain and the ability to perform the activities of daily living were recorded in a dairy via modified WOMAC first on a daily basis, then on each second day and finally once a week for a total of 12 weeks. WOMAC questionnaire and SF-36 were administered at 6 weeks and 3 months follow-up. Results: The groups were similar demographically. Patients in MIDA group had significantly less total blood loss (p = 0.006), postoperative blood levels of creatinine kinase were significantly lower (p = 0.001). Operative time was similar in both groups, we found no difference in component placement. Physical component summary of SF-36 at 12 weeks follow-up showed a significant benefit for the MIDA group. Averaged modified WOMAC scores and their pain and function subscores demonstrated a clear advantage on every recorded day during the first 12 weeks for MIDA. Median WOMAC sum score and respective pain as well as function subscores were better in the MIDA group at 6 and 12 weeks follow up. Conclusions: A minimally invasive direct anterior approach is superior to a conventional lateral transgluteal approach with regard to blood loss and
Objectives: To compare the results of various surgical approaches to the knee in primary total knee arthroplasty (TKA) surgery. Design: Systematic review with meta-analysis. Data Sources: Cochrane Bone, Joint, and
Background: The Levels of Evidence Rating System is widely believed to categorize studies by quality, with Level I studies representing the highest quality evidence. We aimed to determine the reporting quality of Randomised Controlled Trials (RCTs) published in the most frequently cited general orthopaedic journals. Methods: Two assessors identified orthopaedic journals that reported a level of evidence rating in their abstracts from January 2003 to December 2004 by searching the instructions for authors of the four highest impact general orthopaedic journals. Based upon a priori eligibility criteria, two assessors hand searched all issues of the eligible journal from 2003–2004 for RCTs. The assessors extracted the demographic information and the evidence rating from each included RCT and scored the quality of reporting using the reporting quality assessment tool, which was developed by the Cochrane Bone, Joint and
Skeletal muscle injuries often lead to severe functional deficits. Mesenchymal stem cell (MSC) therapy is a promising but still experimental tool in the regeneration of muscle function after severe trauma. One of the most important questions, which has to be answered prior to a possible future clinical application is the ideal time of transplantation. Due to the initial inflammatory environment we hypothesized that a local injection of the cells immediately after injury would result in an inferior functional outcome compared to a delayed transplantation. Twenty-seven female Sprague Dawley rats were used for this study. Bone marrow was aspirated from both tibiae of each animal and autologous MSC cultures obtained from the material. The animals were separated into three groups (each n=9) and the left soleus muscles were bluntly crushed in a standardized manner. In group 1 2×106 MSCs were transplanted into the injured muscle immediately after trauma, whereas group 2 and 3 received an injection of saline. Another week later the left soleus muscles of the animals of group 2 were transplanted with the same number of MSCs. Group 1 and 3 received a sham treatment with the application of saline solution in an identical manner. In vivo functional muscle testing was performed four weeks after trauma to quantify muscle regeneration. Maximum contraction forces after twitch stimulation decreased to 39 ± 18 % of the non injured right control side after crush trauma of the soleus muscles as measured in group 3. Tetanic stimulation showed a reduction of the maximum contraction capacity of 72 ± 12 % of the value obtained from intact internal control muscles. The transplantation of 2 x 106 MSCs one week after trauma improved the functional regeneration of the injured muscles as displayed by significantly higher contraction forces in group 2 (twitch: p = 0.014, tetany: p = 0.018). Local transplantation of the same number of MSCs immediately after crush injury was able to enhance the regeneration process to a similar extent with an increase of maximum twitch contraction forces by 73.3 % (p = 0.006) and of maximum tetanic contraction forces by 49.6 % (p = 0.037) compared to the control group. The presented results underline the effectivity of MSC transplantation in the treatment of severe skeletal muscle injuries. The most surprising finding was that despite of the fundamental differences of the local environment into which MSCs had been transplanted, similar results could be obtained in respect to functional skeletal muscle regeneration. We assume that the effect of the MSC after immediate injection can partly be explained by their known immunomodulatory competences. The data of our study provide evidence for a large time window of MSC transplantation after
Background: Autologous mesenchymal stem cells (MSC) have been shown to improve the functional outcome after severe skeletal muscle trauma. The reasons for this improvement have yet not been revealed. Up to now insufficient techniques of cell labelling, which could only be used for histologic analysis ex vivo, have been a problem. The development of iron oxide nanoparticles, which are taken up and endosomally stored by stem cells, allows the evaluation of cellular behaviour in the muscle with the use of magnetic resonance imaging (MRI). Previous work has shown that labelling does not affect the proliferation and neurogenic differentiation capacity of embryonic stem cells. In the present study we are currently investigating the in vivo distribution and migration of locally transplanted MSC after blunt
Dystrophic calcification (DC) is the abnormal appearance of calcified deposits in degenerating tissue, often associated with injury. Extensive DC can lead to heterotopic ossification (HO), a pathological condition of ectopic bone formation. The highest rate of HO was found in combat-related blast injuries, a polytrauma condition with severe muscle injury. It has been noted that the incidence of HO significantly increased in the residual limbs of combat-injured patients if the final amputation was performed within the zone of injury compared to that which was proximal to the zone of injury. While aggressive limb salvage strategies may maximize the function of the residual limb, they may increase the possibility of retaining non-viable muscle tissue inside the body. In this study, we hypothesized that residual dead muscle tissue at the zone of injury could promote HO formation. We tested the hypothesis by investigating the cellular and molecular consequences of implanting devitalized muscle tissue into mouse muscle pouch in the presence of muscle injury induced by cardiotoxin.Aims
Methods