The temporal expression of estrogen receptor alpha-36 and runx2 in human bone marrow derived stromal cells during osteogenesis.

During bone maintenance in vivo, estrogen signals through estrogen receptor (ER)-α. The objectives of this study were to investigate the temporal expression of ERα36 and ascertain its functional relevance during osteogenesis in human bone marrow derived stromal cells (BMSC). This was assessed in relation to runt-related transcription factor-2 (runx2), a main modulatory protein involved in bone formation. ERα36 and runx2 subcellular localisation was assessed using immunocytochemistry, and their mRNA expression levels by real time PCR throughout the process of osteogenesis. The osteogenically induced BMSCs demonstrated a rise in ERα36 mRNA during proliferation followed by a decline in expression at day 10, which represents a change in dynamics within the culture between the proliferative stage and the differentiative stage. The mRNA expression profile of runx2 mirrored that of ERα36 and showed a degree subcellular co-localisation with ERα36. This study suggests that ERα36 is involved in the process of osteogenesis in BMSCs, which has implications in estrogen deficient environments.

The Royal College of Surgeons of England Damage Control Orthopaedic Trauma Skills course (DCOTS): resuscitative knowledge and confidence in surgical skills are reliably maintained at six months post course.

INTRODUCTION: Since 2012, the Damage Control Orthopaedic Trauma Skills course (DCOTS) has trained more than 250 surgeons in the principles and practice of damage control orthopaedics and early appropriate care. This Royal College of Surgeons of England (RCS England) course takes place at the RCS England Partner cadaver laboratory at Brighton and Sussex Medical School. Trauma is a leading cause of morbidity and mortality in the UK, and the course has tried to pass on the lessons of war and conflict from its military faculty and hard-won lessons of "developed world" trauma from its experienced civilian faculty. METHODS: Participating surgeons were invited to score their self-reported confidence before attending the DCOTS course, immediately afterwards and again 6 months later. A modified four-point Likert scale was used, with responses from 1 = No Confidence to 4 = Very Confident. Damage control resuscitation principles with damage control surgery showed the greatest retained increase at 6 months - 100% - which is extremely satisfying. RESULTS: Self-reported confidence in pelvic external fixation was initially 93% dropping to 85%, which is also considered good to excellent. For pelvic packing, confidence was 90% at the end of the course, up from 19% precourse. This dropped to 62%, which was still considered good but low for the high standards of the course. This may relate to UK trainees' lack of familiarity with the concept. CONCLUSIONS: Three of the main skills taught on the DCOTS are effectively retained at 6 months post course.

Altered leucocyte progenitor profile in human bone marrow from patients with major trauma during the recovery phase.

BACKGROUND: Changes in human bone marrow associated with the systemic inflammatory response to injury are little understood. It was hypothesized that major trauma results in an altered bone marrow leucocyte progenitor profile, with either uniform depletion or the balance between multipotent and committed progenitors varying, depending on whether self-renewal is favoured over differentiation. METHODS: Bone marrow aspirate and peripheral blood samples were obtained at definitive surgery in adults with pelvic fractures from blunt trauma (major trauma with Injury Severity Score (ISS) at least 18, or isolated fractures) and control patients undergoing iliac crest bone grafting. ISS, interval to surgery and transfusion in the first 24 h were recorded. Bone marrow aspirate flow cytometry was used to identify haemopoietic progenitor cells (CD34(+) ), multipotent cells (CD34(+) CD45(+) CD38(-) ) and oligopotent cells (CD34(+) CD45(+) CD38(lo/+) and CD34(+) CD45(+) CD38(BRIGHT(++ +)) subsets). Peripheral blood levels of inflammatory markers were measured, and the ratio of immature to mature (CD35(-) /CD35(+) ) granulocytes was determined. RESULTS: The median (range) interval between injury and sampling was 7 (1-21) and 5 (1-21) days in the major trauma and isolated fracture groups respectively. The CD34(+) pool was significantly depleted in the major trauma group (P = 0·017), particularly the CD34(+) CD45(+) CD38(BRIGHT(++ +)) oligopotent pool (P = 0·003). Immature CD35(-) granulocytes increased in bone marrow with increasing injury severity (P = 0·024) and massive transfusion (P = 0·019), and in peripheral blood with increasing interval to surgery (P = 0·005). CONCLUSION: Major blunt trauma resulted in changes in the bone marrow CD34(+) progenitor pool. At the point in recovery when these samples were obtained, oligopotent progenitors were lost from the bone marrow, with continued release of immature cells.

An investigation of the transmission and attenuation of intense pulsed light on samples of human Achilles tendon and surrounding tissue.

BACKGROUND: Light therapy is a common mode of treatment for musculoskeletal injuries but the depth of penetration of light radiation is controversial. Evidence exists for the efficacy of intense pulsed light (IPL) treatment for the rejuvenation of skin (superficial tissue) but it is not known if the IPL can penetrate deeper. If the IPL can penetrate to the depth of the Achilles tendon it may provide a potential management options in the treatment of a chronic mid-body Achilles tendinopathy. OBJECTIVES: To examine if any optical radiation produced by an IPL transmits to the depth of the Achilles tendon when applied cutaneously to excised samples of human Achilles tissue. A secondary aim was to establish the relative amount of optical radiation that was attenuated within the tendon. MATERIALS AND METHODS: Three samples of human Achilles tendon and surrounding tissue were harvested following elective lower limb amputation operations. Each sample was irradiated 2-6 cm above the insertion into the calcaneus (area of an Achilles tendinopathy) with IPL (model iPulse; Cyden Ltd, Wales, UK) set at a single pulse of 25 millisecond, wavelength range 530-1,110 nm and fluence of 13 J/cm(2). The transmission of light radiation was evaluated using (a) standard SLR digital camera, (b) spectrometer, and (c) an external energy meter. RESULTS: Light radiation was found to have transmitted through each of the three tissue samples by all three instruments. There were observable differences in the color of light detected for the control photo and the IPL irradiated tissue samples photographs. The percentage of fluence that was detected to have transmitted through the tissue samples by the energy meter was 4-8.1% and wavelengths between 645 and 843 nm were detected to have transmitted through the tissue by the spectrometer. In addition, the percentage of light radiation that attenuated with the tendon was 10.2-17.32%. CONCLUSION: The results of this study provides evidence that IPL penetrates to the depth of the Achilles tendon and attenuates with the tendon. IPL has potential to produce physiological effects in the treatment of patients with a chronic mid-body Achilles tendinopathy.

Bringing damage control surgery simulation to life: developing a novel surgical anatomy model within immersive military trauma surgery simulation.

Haemorrhage from junctional injuries remains the most common cause of battlefield death. Changes to surgical training have meant acquiring and maintaining trauma surgical skills is becoming more difficult for military surgeons. The multidisciplinary Military Operational Specialist Team Training (MOSTT) course is designed to bridge the gap between civilian practice and the deployed environment, as part of predeployment trauma training. It involves immersive team simulation and uses cadaveric dissection for surgical skills practice.A novel surgical anatomy model, featuring junctional haemorrhage surgical task trainers of the groin and shoulder, was designed using reconstructed CT and MRI images obtained from a human volunteer. The model is designed to look and feel as realistic as possible, with the added dimension of pulsatile 'blood' flow from a simulation gunshot injury.This surgical anatomy model has been trialled, as part of the MOSTT course, by 90 surgeons and perioperative practitioners, with feedback analysis used for iterative model development. Feedback demonstrated that, alongside more traditional cadaveric dissection, this surgical anatomy model adds value to current predeployment training delivered within the immersive simulation of the MOSTT course. Research by the authors about the effects of this model on surgical ability and performance is ongoing. However, there is clear potential for this model to be used in other environments, including on exercises and as part of consolidation training while deployed.

Measuring outcomes following tibial fracture.

AIM: The aim of this study was to determine how outcome is measured following adult tibial fracture in the modern era of functional outcome measurement and patient reported outcomes. METHODS: A systematic review of publications since 2009 was performed, looking specifically at acute, adult tibial shaft fractures. Ovid Medline, Embase, PubMed and PsycINFO databases were searched for relevant titles which were then screened by two authors with adjudication where necessary by a third. Relevant articles were reviewed in full and data was extracted concerning the study participants, study design and any measures that were used to quantify the results following fracture. The results were collated and patient reported outcome measures were assessed using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) standards. RESULTS: A total of 943 titles and articles were reviewed, with 117 included for full analysis. A wide range of clinical and radiological "outcomes" were described, along with named clinician- and patient-reported outcome measures. There was considerable heterogeneity and lack of detail in the description of the simplest outcomes, such as union, infection or reoperation. Reported clinician and patient reported outcome measures are variably used. None of the identified patient reported outcome measures have been validated for use following tibial fracture. CONCLUSION: We recommend definition of a core outcome set for use following tibial fracture. This will standardise outcome reporting following these injuries. Furthermore, there is need for a validated patient reported outcome measure to better assess patient important outcomes in this patient group.

Open tibial fractures in major trauma centres: A national prospective cohort study of current practice.

AIMS: To assess current national practice in the management of severe open tibial fractures against national standards, using data collected by the Trauma and Audit Research Network. MATERIALS AND METHODS: Demographic, injury-specific, and outcome data were obtained for all grade IIIB/C fractures admitted to Major Trauma Centres in England from October 2014 to January 2016. RESULTS: Data was available for 646 patients with recorded grade IIIB/C fractures. The male to female ratio was 2.3:1, mean age 47 years. 77% received antibiotics within 3 h of admission, 82% were debrided within 24 h. Soft tissue coverage was achieved within 72 h of admission in 71%. The amputation rate was 8.7%. 4.3% of patients required further theatre visits for infection during the index admission. The timing of antibiotics and surgery could not be correlated with returns to theatre for early infection. There were significant differences in the management and outcomes of patients aged 65 and over, with an increase in mortality and amputation rates. CONCLUSIONS: Good outcomes are reported from the management of IIIB/C fractures in Major Trauma Centres in England. Overall compliance with national standards is particularly poor in the elderly. Compliance did not appear to affect rates of returning to theatre or early infection. Appropriately applied patient reported outcome measures are needed to enhance the evidence-base for management of these injuries.

Motorcyclists and pillion passengers with open lower-limb fractures: a study using TARN data 2007-2014.

Introduction We aimed to identify population demographics of motorcyclists and pillion passengers with isolated open lower-limb fractures, to ascertain the impact of the revised 2009 British Orthopaedic Association/British Association of Plastic Reconstructive and Aesthetic Surgeons joint standards for the management of open fractures of the lower limb (BOAST 4), in terms of time to skeletal stabilisation and soft-tissue coverage, and to observe any impact on patient movement. Methods Retrospective cohort data was collected by the Trauma Audit and Research Network (TARN). A longitudinal analysis was performed between two timeframes in England (pre-and post-BOAST 4 revision): 2007-2009 and 2010-2014. Results A total of 1564 motorcyclists and 64 pillion passengers were identified. Of these, 93% (1521/1628) were male. The median age for males was 30.5 years and 36.7 years for females. There was a statistically significant difference in the number of patients who underwent skeletal stabilisation (49% vs 65%, P < 0.0001), the time from injury to skeletal stabilisation (7.33 hours vs 14.3 hours, P < 0.0001) and the proportion receiving soft-tissue coverage (26% vs 43%, P < 0.0001). There was no difference in the time from injury to soft-tissue coverage (62.3 hours vs 63.7 hours, P = 0.726). The number of patients taken directly to a major trauma centre (or its equivalent) increased between the two timeframes (12.5% vs, 41%, P < 0.001). Conclusions Since the 2009 BOAST 4 revision, there has been no difference in the time taken from injury to soft-tissue coverage but the time from injury to skeletal stabilisation is longer. There has also been an increase in patient movement to centres offering joint orthopaedic and plastic care.

Induced membrane technique for treating tibial defects gives mixed results.

AIMS: This study describes the use of the Masquelet technique to treat segmental tibial bone loss in 12 patients. PATIENTS AND METHODS: This retrospective case series reviewed 12 patients treated between 2010 and 2015 to determine their clinical outcome. Patients were mostly male with a mean age of 36 years (16 to 62). The outcomes recorded included union, infection and amputation. The mean follow-up was 675 days (403 to 952). RESULTS: The mean tibial defect measured 5.8 cm (2 to 15) in length. Of the 12 patients, 11 had an open fracture. Eight underwent fixation with an intramedullary nail, three with plates and one with a Taylor Spatial Frame. The mean interval between stages was 57 days (35 to 89). Bony union was achieved in only five patients. Five patients experienced infective complications during treatment, with two requiring amputation because of severe infection. CONCLUSION: The Masquelet technique was relatively ineffective in achieving union in this series, and was associated with a high rate of infection. Cite this article: Bone Joint J 2017;99-B:680-5.

Demystifying damage control in musculoskeletal trauma.

Trauma care has evolved rapidly over the past decade. The benefits of operative fracture management in major trauma patients are well recognised. Concerns over early total care arose when applied broadly. The burden of additional surgical trauma could constitute a second hit, fuelling the inflammatory response and precipitating a decline into acute respiratory distress syndrome, sepsis and multiple organ dysfunction syndrome. Temporary external fixation aimed to deliver the benefits of fracture stabilisation without the risk of major surgery. This damage control orthopaedics approach was advocated for those in extremis and a poorly defined borderline group. An increasing understanding of the physiological response to major trauma means there is now a need to refine our treatment options. A number of large scale retrospective reviews indicate that early definitive fracture fixation is beneficial in the majority of major trauma patients. It is recommended that patients are selected appropriately on the basis of their response to resuscitation. The hope is that this approach (dubbed 'safe definitive fracture surgery' or 'early appropriate care') will herald an era when care is individualised for each patient and their circumstances. The novel Damage Control in Orthopaedic Trauma Surgery course at The Royal College of Surgeons of England aims to equip senior surgeons with the insights and mindset necessary to contribute to this key decision making process as well as also the technical skills to provide damage control interventions when needed, relying on the improved techniques of damage control resuscitation and advances in the understanding of early appropriate care.

From guidelines to standards of care for open tibial fractures.

INTRODUCTION: The standards for the management of open fractures of the lower limb published by the British Association of Plastic, Reconstructive and Aesthetic surgeons (BAPRAS) and British Orthopaedic Association (BOA) were introduced to improve the treatment received by patients after open injury to the lower limb. These Standards were released after BAPRAS/BOA published Guidelines for the management of open tibial fractures. METHODS: We wished to determine the impact of these Standards upon the surgical management of open tibial fractures by comparing patients admitted to an orthoplastic centre in the 45 months concluding December 2009 (the Guidelines era) with those admitted during 2011 (the Standards era). Surgical procedures required during the first 30 days and 12 months after injury were determined. Cases were divided into 'directly admitted patients' (DAP) and 'transferred patients' (TP). Standards-era patients were divided further into those who had surgery exclusively at the orthoplastic centre (orthoplastic patients (OPP)) and those transferred after surgery (TASP). RESULTS: The number of TP trebled in frequency in the Standards era, 25% of whom were transferred before surgery. Significantly fewer surgical procedures were required for DAP and OPP groups compared with TP (and TASP) groups in both eras (Mann-Whitney U-test, p=0.05). DAP and OPP groups during the Standards era underwent the fewest procedures, with the vast majority of cases treated with two or fewer procedures in the first 12 months (88% and 80%, respectively, compared with 61% in the Guidelines era). In the Guidelines era, 44% of TP cases and in the Standards era 39% of TP and 29% of TASP groups underwent two or fewer procedures. Approximately two-thirds of open tibial fractures managed in our orthoplastic centre were patients transferred after surgery. The greatest impact of the Standards was evident for those who underwent surgery exclusively in the orthoplastic centre, reflecting a more deliberate combined strategy. CONCLUSION: These findings vindicate the Standards as well as mandating reorganisation and resourcing of orthoplastic services to ensure immediate transfer and early combined surgery. By increasing the capacity to deal with time-dependent initial surgery, the surgical burden that the patient must endure, and which the service must provide, are reduced.

Management of open lower limb injuries in South West England and Wales.

INTRODUCTION: The joint British Association of Plastic, Reconstructive and Aesthetic Surgeons/British Orthopaedic Association standards define best practice management in open diaphyseal fractures of the lower limb. The aim of our study was to review the regional approach and experience in South West England and Wales. A further objective was to evaluate service provision with regard to the standards' key recommendations. METHODS: A prospective audit was undertaken of open diaphyseal fracture patients. Compliance with published standards within all orthoplastic services in South West England and Wales was assessed, and facilities were evaluated. RESULTS: A total of 86 patients were managed between October 2012 and March 2013. This was a 56% increase from 2008. Over half (56%) presented directly to the orthoplastic services with all patients undergoing debridement within 24 hours. Two-thirds (66%) of procedures were in daylight hours excluding those requiring immediate surgical intervention. Adherence to correct antibiotic therapy was 88% at admission, 50% at primary surgery and 62% at definitive surgery. Almost two-thirds (60%) of primary procedures were performed with combined senior orthoplastic teams, with 81% achieving definitive soft tissue coverage and fixation within seven days. Compliance improved in units with larger patient caseloads and where there was an early combined approach during daylight hours. CONCLUSIONS: Increased open lower limb fracture workload was demonstrated across South West England and Wales, probably owing to centralisation of trauma services. An improvement in early transfer of this patient group to orthoplastic facilities has allowed all patients to be assessed and debrided within the recommended timeframe. Standards were most likely to be met in those centres seeing higher numbers of injuries and when there was a daylight hours procedure by combined orthoplastic teams.

Cholelithoptysis and empyema formation after laparoscopic cholecystectomy.

Thoracic complications of laparoscopic operations are rare. We describe a case of cholelithoptysis due to a gallstone sequestered in the middle lobe after laparoscopic cholecystectomy.

Intense pulsed light treatment of chronic mid-body Achilles tendinopathy: A double blind randomised placebo-controlled trial.

We conducted a randomised controlled trial to determine whether active intense pulsed light (IPL) is an effective treatment for patients with chronic mid-body Achilles tendinopathy. A total of 47 patients were randomly assigned to three weekly therapeutic or placebo IPL treatments. The primary outcome measure was the Victorian Institute of Sport Assessment - Achilles (VISA-A) score. Secondary outcomes were a visual analogue scale for pain (VAS) and the Lower Extremity Functional Scale (LEFS). Outcomes were recorded at baseline, six weeks and 12 weeks following treatment. Ultrasound assessment of the thickness of the tendon and neovascularisation were also recorded before and after treatment. There was no significant difference between the groups for any of the outcome scores or ultrasound measurements by 12 weeks, showing no measurable benefit from treatment with IPL in patients with Achilles tendinopathy.

Orthopaedic trauma research priority-setting exercise and development of a research network.

INTRODUCTION: Clinical practice should be informed by high quality evidence, of which randomised controlled trials (RCTs) are considered the gold standard. Surgical trials are inherently difficult with potential problems around clinical equipoise and participant acceptability. This is often most true with trial designs comparing operative and non-operative treatments. It is hoped that research activity can be maximised by collaborating in (a) the identification of research questions and (b) involvement in clinical trials. Development of the national research networks can be utilised to provide support for research endeavours within the orthopaedic trauma community. AIMS: To identify and prioritise the research questions felt to be of most importance by the orthopaedic trauma community. Research studies will be considered for questions given the highest priority. METHODS: A Delphi approach was used to determine consensus between the faculty members of the AOUK. A two round process was used to elicit the research questions and then to rank them in order of priority. RESULTS: 217 members of the AOUK Long Bone Faculty were asked to submit research questions, predominantly consultant orthopaedic surgeons. A 22% response rate generated 147 questions. These were collated and the most frequent 24 sent back out for ranking by mean scores. A 55% response to this second round identified 10 top questions. Literature searches for these 10 looked at current knowledge of the subject, completed and ongoing research projects. We also looked at the advantages and disadvantages of undertaking a study and the most appropriate methodology. CONCLUSION: The response rates demonstrated a clear interest in developing a collaborative research strategy. This can be enhanced by utilising the support of the National Institute of Health Research Clinical Research Networks (NIHR CRN).