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1.  The systemic influence of platelet-derived growth factors on bone marrow mesenchymal stem cells in fracture patients 
BMC Medicine  2015;13:6.
Fracture healing is a complex process regulated by a variety of cells and signalling molecules which act both locally and systemically. The aim of this study was to investigate potential changes in patients’ mesenchymal stem cells (MSCs) in the iliac crest (IC) bone marrow (BM) and in peripheral blood (PB) in relation to the severity of trauma and to correlate them with systemic changes reflective of inflammatory and platelet responses following fracture.
ICBM samples were aspirated from two trauma groups: isolated trauma and polytrauma (n = 8 and 18, respectively) at two time-points post-fracture and from non-trauma controls (n = 7). Matched PB was collected every other day for a minimum of 14 days. BM MSCs were enumerated using colony forming-fibroblast (CFU-F) assay and flow cytometry for the CD45-CD271+ phenotype.
Regardless of the severity of trauma, no significant increase or decrease in BM MSCs was observed following fracture and MSCs were not mobilised into PB. However, direct positive correlations were observed between changes in the numbers of aspirated BM MSCs and time-matched changes in their serum PDGF-AA and -BB. In vitro, patients’ serum induced MSC proliferation in a manner reflecting changes in PDGFs. PDGF receptors CD140a and CD140b were expressed on native CD45-CD271+ BM MSCs (average 12% and 64%, respectively) and changed over time in direct relationship with platelets/PDGFs.
Platelet lysates and other platelet-derived products are used to expand MSCs ex vivo. This study demonstrates that endogenous PDGFs can influence MSC responses in vivo. This indicates a highly dynamic, rather than static, MSC nature in humans.
Electronic supplementary material
The online version of this article (doi:10.1186/s12916-014-0202-6) contains supplementary material, which is available to authorized users.
PMCID: PMC4293103  PMID: 25583409
Mesenchymal stem cells; MSCs; Bone marrow; PDGF; Platelets
2.  Outcomes of polytrauma patients with diabetes mellitus 
BMC Medicine  2014;12:111.
The impact of diabetes mellitus in patients with multiple system injuries remains obscure. This study was designed to increase knowledge of outcomes of polytrauma in patients who have diabetes mellitus.
Data from the Trauma Audit and Research Network was used to identify patients who had suffered polytrauma during 2003 to 2011. These patients were filtered to those with known outcomes, then separated into those with diabetes, those known to have other co-morbidities but not diabetes and those known not to have any co-morbidities or diabetes. The data were analyzed to establish if patients with diabetes had differing outcomes associated with their diabetes versus the other groups.
In total, 222 patients had diabetes, 2,558 had no past medical co-morbidities (PMC), 2,709 had PMC but no diabetes. The diabetic group of patients was found to be older than the other groups (P <0.05). A higher mortality rate was found in the diabetic group compared to the non-PMC group (32.4% versus 12.9%), P <0.05). Rates of many complications including renal failure, myocardial infarction, acute respiratory distress syndrome, pulmonary embolism and deep vein thrombosis were all found to be higher in the diabetic group.
Close monitoring of diabetic patients may result in improved outcomes. Tighter glycemic control and earlier intervention for complications may reduce mortality and morbidity.
PMCID: PMC4223424  PMID: 25026864
Polytrauma; Trauma; Diabetes mellitus; TARN; Trauma Audit and Research Network
3.  A cohort study on the incidence and outcome of pulmonary embolism in trauma and orthopedic patients 
BMC Medicine  2014;12:39.
This study aims to determine the incidence of pulmonary embolism (PE) in trauma and orthopedic patients within a regional tertiary referral center and its association with the pattern of injury, type of treatment, co-morbidities, thromboprophylaxis and mortality.
All patients admitted to our institution between January 2010 and December 2011, for acute trauma or elective orthopedic procedures, were eligible to participate in this study. Our cohort was formed by identifying all patients with clinical features of PE who underwent Computed Tomography-Pulmonary Angiogram (CT-PA) to confirm or exclude the clinical suspicion of PE, within six months after the injury or the surgical procedure.
Case notes and electronic databases were reviewed retrospectively to identify each patient’s venous thromboembolism (VTE) risk factors, type of treatment, thromboprophylaxis and mortality.
Out of 18,151 patients admitted during the study period only 85 (0.47%) patients developed PE (positive CT-PA) (24 underwent elective surgery and 61 sustained acute trauma). Of these, only 76% of the patients received thromboprophylaxis. Hypertension, obesity and cardiovascular disease were the most commonly identifiable risk factors. In 39% of the cases, PE was diagnosed during the in-hospital stay. The median time of PE diagnosis, from the date of injury or the surgical intervention was 23 days (range 1 to 312). The overall mortality rate was 0.07% (13/18,151), but for those who developed PE it was 15.29% (13/85). Concomitant deep venous thrombosis (DVT) was identified in 33.3% of patients. The presence of two or more co-morbidities was significantly associated with the incidence of mortality (unadjusted odds ratio (OR) = 3.52, 95% confidence interval (CI) (1.34, 18.99), P = 0.034). Although there was also a similar clinical effect size for polytrauma injury on mortality (unadjusted OR = 1.90 (0.38, 9.54), P = 0.218), evidence was not statistically significant for this factor.
The incidence of VTE was comparable to previously reported rates, whereas the mortality rate was lower. Our local protocols that comply with the National Institute for Health and Clinical Excellence (NICE) guidelines in the UK appear to be effective in preventing VTE and reducing mortality in trauma and orthopedic patients.
PMCID: PMC3996019  PMID: 24589368
Pulmonary embolism; Deep venous thrombosis; Trauma; Orthopedic surgery; Arthroplasty; Mortality; Incidence
4.  The role of barrier membranes for guided bone regeneration and restoration of large bone defects: current experimental and clinical evidence 
BMC Medicine  2012;10:81.
Treatment of large bone defects represents a great challenge in orthopedic and craniomaxillofacial surgery. Although there are several methods for bone reconstruction, they all have specific indications and limitations. The concept of using barrier membranes for restoration of bone defects has been developed in an effort to simplify their treatment by offering a sinlge-staged procedure. Research on this field of bone regeneration is ongoing, with evidence being mainly attained from preclinical studies. The purpose of this review is to summarize the current experimental and clinical evidence on the use of barrier membranes for restoration of bone defects in maxillofacial and orthopedic surgery. Although there are a few promising preliminary human studies, before clinical applications can be recommended, future research should aim to establish the 'ideal' barrier membrane and delineate the need for additional bone grafting materials aiming to 'mimic' or even accelerate the normal process of bone formation. Reproducible results and long-term observations with barrier membranes in animal studies, and particularly in large animal models, are required as well as well-designed clinical studies to evaluate their safety, efficacy and cost-effectiveness.
PMCID: PMC3423057  PMID: 22834465
bone regeneration; bone defect; barrier membranes; non-resorbable membranes; bioresorbable/absorbable membranes
5.  Trauma networks: present and future challenges 
BMC Medicine  2011;9:121.
In England, trauma is the leading cause of death across all age groups, with over 16,000 deaths per year. Major trauma implies the presence of multiple, serious injuries that could result in death or serious disability. Successive reports have documented the fact that the current ad hoc unstructured management of this patient group is associated with considerable avoidable death and disability. The reform of trauma care in England, especially of the severely injured patient, has already begun. Strong clinical leadership is embraced as the way forward. The present article summarises the steps that have been made over the last decade that led to the recent decision to move towards a long anticipated restructure of the National Health Service (NHS) trauma services with the introduction of Regional Trauma Networks (RTNs). While, for the first time, a genuine political will and support exists, the changes required to maintain the momentum for the implementation of the RTNs needs to be marshalled against arguments, myths and perceptions from the past. Such an approach may reverse the disinterest attitude of many, and will gradually evolve into a cultural shift of the public, clinicians and policymakers in the fullness of time.
PMCID: PMC3229440  PMID: 22078223
6.  Bone regeneration: current concepts and future directions 
BMC Medicine  2011;9:66.
Bone regeneration is a complex, well-orchestrated physiological process of bone formation, which can be seen during normal fracture healing, and is involved in continuous remodelling throughout adult life. However, there are complex clinical conditions in which bone regeneration is required in large quantity, such as for skeletal reconstruction of large bone defects created by trauma, infection, tumour resection and skeletal abnormalities, or cases in which the regenerative process is compromised, including avascular necrosis, atrophic non-unions and osteoporosis. Currently, there is a plethora of different strategies to augment the impaired or 'insufficient' bone-regeneration process, including the 'gold standard' autologous bone graft, free fibula vascularised graft, allograft implantation, and use of growth factors, osteoconductive scaffolds, osteoprogenitor cells and distraction osteogenesis. Improved 'local' strategies in terms of tissue engineering and gene therapy, or even 'systemic' enhancement of bone repair, are under intense investigation, in an effort to overcome the limitations of the current methods, to produce bone-graft substitutes with biomechanical properties that are as identical to normal bone as possible, to accelerate the overall regeneration process, or even to address systemic conditions, such as skeletal disorders and osteoporosis.
PMCID: PMC3123714  PMID: 21627784
7.  Pregnancy-related pelvic girdle pain: an update 
BMC Medicine  2011;9:15.
A large number of scientists from a wide range of medical and surgical disciplines have reported on the existence and characteristics of the clinical syndrome of pelvic girdle pain during or after pregnancy. This syndrome refers to a musculoskeletal type of persistent pain localised at the anterior and/or posterior aspect of the pelvic ring. The pain may radiate across the hip joint and the thigh bones. The symptoms may begin either during the first trimester of pregnancy, at labour or even during the postpartum period. The physiological processes characterising this clinical entity remain obscure. In this review, the definition and epidemiology, as well as a proposed diagnostic algorithm and treatment options, are presented. Ongoing research is desirable to establish clear management strategies that are based on the pathophysiologic mechanisms responsible for the escalation of the syndrome's symptoms to a fraction of the population of pregnant women.
PMCID: PMC3050758  PMID: 21324134

Results 1-7 (7)