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1.  Ability of bone graft substitutes to support the osteoprogenitor cells: An in-vitro study 
World Journal of Stem Cells  2014;6(4):497-504.
AIM: To compare seven commercially available bone graft substitutes (BGS) in terms of these properties and without using any additional biological growth factors.
METHODS: Porcine osteoprogenitor cells were loaded on seven commercially available BGS and allowed to proliferate for one week followed by osteogenic induction. Staining for live/dead cells as well as scanning electron microscopy (SEM) was carried out to determine viability and cellular binding. Further outcome measures included alkaline phosphatase (ALP) assays with normalisation for DNA content to quantify osteogenic potential. Negative and positive control experiments were carried out in parallel to validate the results.
RESULTS: Live/dead and SEM imaging showed higher viability and attachment with β-tricalcium phosphate (β-TCP) than with other BGS (P < 0.05). The average ALP activity in nmol/mL (normalised value for DNA content in nmol/μg DNA) per sample was 657.58 (132.03) for β-TCP, 36.22 (unable to normalise) for calcium sulphate, 19.93 (11.39) for the Hydroxyapatite/Tricalcium Phosphate composite, 14.79 (18.53) for polygraft, 13.98 (8.15) for the highly porous β-Tricalcium Phosphate, 5.56 (10.0) for polymers, and 3.82 (3.8) for Hydroxyapatite.
CONCLUSION: Under the above experimental conditions, β-TCP was able to maintain better the viability of osteoprogenitor cells and allow proliferation and differentiation (P < 0.05).
PMCID: PMC4172679  PMID: 25258672
Bone graft; Bone graft substitute; Osteoprogenitor cells; Fracture healing; Bone
2.  The genetic profile of bone repair 
Bone repair following a fracture is a complex, well orchestrated, physiological process in response to injury. Even though the exact number of the genes and expressed proteins involved in fracture healing remains unknown, the molecular complexity of the repair process has been demonstrated, and it involves numerous genes and molecules, such as extracellular matrix genes, growth and differentiation factors, matrix metalloproteinases, angiogenic factors and others. Discrepancies in fracture healing responses and final outcome seen in the clinical practice may be attributed among other factors to biological variations between patients and different genetic “profiles”, resulting in “altered” signalling pathways that regulate the bone repair process. Preliminary human studies support a “genetic” component in the pathophysiology of impaired bone repair seen in atrophic non-unions by correlating genetic variations of specific molecules regulating fracture healing with non-union. However, the role of the genetic “profile” of each individual in fracture healing and final outcome, and its possible interaction with other exogenous factors remains a topic of extensive research.
PMCID: PMC3710004  PMID: 23858305
genetic profile; genetic variation; bone repair; fracture healing
3.  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
4.  Multipotential stromal cell abundance in cellular bone allograft: comparison with fresh age-matched iliac crest bone and bone marrow aspirate 
Regenerative medicine  2014;9(5):593-607.
To enumerate and characterize multipotential stromal cells (MSCs) in a cellular bone allograft and compare with fresh age-matched iliac crest bone and bone marrow (BM) aspirate.
Materials & methods
MSC characterization used functional assays, confocal/scanning electron microscopy and whole-genome microarrays. Resident MSCs were enumerated by flow cytometry following enzymatic extraction.
Allograft material contained live osteocytes and proliferative bone-lining cells defined as MSCs by phenotypic and functional capacities. Without cultivation/expansion, the allograft displayed an ‘osteoinductive’ molecular signature and the presence of CD45−CD271+CD73+CD90+CD105+ MSCs; with a purity over 100-fold that of iliac crest bone. In comparison with BM, MSC numbers enzymatically released from one gram of cellular allograft were equivalent to approximately 45 ml of BM aspirate.
Cellular allograft bone represents a unique nonimmune material rich in MSCs and osteocytes. This osteoinductive graft represents an attractive alternative to autograft bone or composite/synthetic grafts in orthopedics and broader regenerative medicine settings.
PMCID: PMC4077757  PMID: 24617969
bone marrow; cellular allograft; multipotential stromal cells; osteocytes
5.  Do Nonsteroidal Anti-Inflammatory Drugs Affect Bone Healing? A Critical Analysis 
The Scientific World Journal  2012;2012:606404.
Nonsteroidal anti-inflammatory drugs (NSAIDs) play an essential part in our approach to control pain in the posttraumatic setting. Over the last decades, several studies suggested that NSAIDs interfere with bone healing while others contradict these findings. Although their analgesic potency is well proven, clinicians remain puzzled over the potential safety issues. We have systematically reviewed the available literature, analyzing and presenting the available in vitro animal and clinical studies on this field. Our comprehensive review reveals the great diversity of the presented data in all groups of studies. Animal and in vitro studies present so conflicting data that even studies with identical parameters have opposing results. Basic science research defining the exact mechanism with which NSAIDs could interfere with bone cells and also the conduction of well-randomized prospective clinical trials are warranted. In the absence of robust clinical or scientific evidence, clinicians should treat NSAIDs as a risk factor for bone healing impairment, and their administration should be avoided in high-risk patients.
PMCID: PMC3259713  PMID: 22272177
6.  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
7.  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
8.  Assessment of Lateral Compression type 1 pelvic ring injuries by intraoperative manipulation: which fracture pattern is unstable? 
International Orthopaedics  2012;36(12):2553-2558.
We performed a prospective study to document, by intra-operative manipulation under anaesthesia (MUA) of the pelvic ring, the stability of lateral compression type 1 injuries that were managed in a Level-I Trauma Centre. The documentation of the short-term outcome of the management of these injuries was our secondary aim.
A total of 63 patients were included in the study. Thirty-five patients (group A) were treated surgically whereas 28 (group B) were managed nonoperatively. Intraoperative rotational instability, evident by more than two centimetres of translation during the manipulation manoeuvre, was combined with a complete sacral fracture in all cases.
A statistically significant difference was present between the length of hospital stay, the time to independent pain-free mobilisation, post-manipulation pain levels and opioid requirements between the two groups, with group A demonstrating significantly decreased values in all these four variables (p < 0.05). There was also a significant difference between the pre- and 72-hour post-manipulation visual analogue scale and analgesic requirements of the group A patients, whereas the patients in group B did not demonstrate such a difference.
LC-1 injuries with a complete posterior sacral injury are inheritably rotationally unstable and patients presenting with these fracture patterns definitely gain benefit from surgical stabilisation.
PMCID: PMC3508039  PMID: 23096135
9.  Nonunion of fibula: a systematic review 
International Orthopaedics  2012;36(9):1757-1765.
The purpose of this systematic review was to analyse the available evidence regarding nonunions of the fibula. We focussed on the incidence, risk factors, evaluation, and treatment modalities for fibular nonunions as evident in the current literature and propose a treatment algorithm.
This was an Institutional Review Board (IRB) exempt study performed at a level one trauma centre. We systematically reviewed the published evidence on fibular nonunion or delayed union from 1950 to February, 2011.
Twelve articles were included in this systematic review. In summary, nonunion of the fibula is becoming increasingly more common in association with intramedullary nailing of concomitant tibial shaft fractures. A treatment algorithm for nonunion of the fibula has been proposed.
The suspicion for nonunion of the fibula should be heightened in lower leg fractures if the patient is symptomatic, and the progression of healing is not as expected. Ideally, prospective, multicentre studies would be performed to provide more rigorous data on the incidence, risk factors, and optimum treatment.
PMCID: PMC3427429  PMID: 22643795
10.  Reconstruction of iliac crest with bovine cancellous allograft after bone graft harvest for symphysis pubis arthrodesis 
International Orthopaedics  2012;36(8):1701-1707.
The aim of this study was to evaluate the safety and efficiency, as well as the incorporation characteristics of a specific type of xenograft used for iliac crest defects post-harvesting tri-cortical iliac crest bone graft.
Sixteen patients diagnosed with chronic anterior pelvic pain were operated for pubic symphysis fusion. The tri-cortical graft harvested from the iliac crest was inserted into the pubic symphysis and compressed with a reconstruction plate. The defect in the iliac crest was filled with a block of cancellous bovine substitute (Tutobone®). The length of iliac crest defect, time to fusion of pubic symphysis, time to incorporation of the graft and complications were recorded. The postoperative pain and patients’ satisfaction were evaluated.
The median age of patients was 36.5 years (range 27–75). Fusion was obtained in 15 patients (94 %). The median time to fusion was four months (range three to seven). The length of the iliac crest bone defect ranged from 40 to 70 mm. Integration of the bovine substitute was achieved in 15 patients (94 %) over a median period of three months (range two to six). The postoperative median pain score was 2 (range 1–5). Twelve patients (75 %) reported good satisfaction. No major complications or allergic reactions were observed.
The xenograft used in this study provided a safe and effective method of reconstruction of iliac crest donor site defects. It has satisfactory incorporation, high biocompatibility and no signs of inflammatory reactions. This new technique is simple and easily reproducible in routine clinical practice.
PMCID: PMC3535019  PMID: 22729663
12.  Release of growth factors and the effect of age, sex, and severity of injury after long bone fracture 
Acta Orthopaedica  2013;84(1):65-70.
Background and purpose
The systemic response after fracture is regulated by a complex mechanism involving numerous growth factors. In this study, we analyzed the kinetics of key growth factors following lower-limb long bone fracture.
Materials and methods
Human serum was isolated from 15 patients suffering from lower-limb long bone fracture (tibia/femur) requiring surgical fixation. The levels of platelet-derived growth factor (PDGF-BB), vascular edothelial growth factor (VEGF), insulin growth factor-I (IGF-I), and transforming growth factor β1 (TGF-β1) were assayed by colorimetric ELISA at different time points during the first week after fracture. 10 healthy volunteers made up the control group of the study. Serum levels of the growth factors measured were compared to age, sex, and injury severity score.
We found that there was a decline in the levels of PDGF-BB, IGF-I and TGF-β1 during the first 3 days after fracture. However, VEGF levels remained unchanged. The levels of all the growth factors studied then increased, with the highest concentrations noted at day 7 after surgery. No correlation was found between circulating levels of growth factors and age, injury severity score (ISS), blood loss, or fluid administration.
There are systemic mitogenic and osteogenic signals after fracture. Important growth factors are released into the peripheral circulation, but early after surgery it appears that serum levels of key growth factors fall. By 7 days postoperatively, the levels had increased considerably. Our findings should be considered in cases where autologous serum is used for ex vivo expansion of mesenchymal stem cells. There should be further evaluation of the use of these molecules as biomarkers of bone union.
PMCID: PMC3584605  PMID: 23343371
13.  Management of Infection After Intramedullary Nailing of Long Bone Fractures: Treatment Protocols and Outcomes 
Implant related sepsis is a relatively unusual complication of intra-medullary nail fixation of long bone fractures. Depending on the extent of infection, timing of diagnosis and progress of fracture union, different treatment strategies have been developed. The aim of this review article is to collect and analyze the existing evidence about the incidence and management of infection following IM nailing of long bone fractures and to recommend treatment algorithms that could be valuable in everyday clinical practice. After searching the P u b M e d /Medline databases, 1270 articles were found related to the topic during the last 20 years. The final review included 28 articles that fulfilled the inclusion criteria.
Only a few prospective studies exist to report on the management of infection following IM nailing of long-bone fractures. In general, stage I (early) infections only require antibiotic administration with/without debridement. Stage II (delayed) infections can be successfully treated with debridement, IM reaming, antibiotic nails, and administration of antibiotics. Infected non-unions are best treated with exchange nailing, antibiotic administration and when infection has been eradicated with graft implantation if it is needed. Debridement, exchange nailing and systemic administration of antibiotics is the best indication for stage III (late) infections, while stage III infected non-unions can successfully be treated with nail removal and Ilizarov frame, especially when large bone defects exist.
PMCID: PMC3731810  PMID: 23919097
Intramedullary nailing; infection; long bone fractures; reaming; review.
14.  “Internal fixation of proximal humeral fractures using the Polarus intramedullary nail: our institutional experience and review of the literature” 
The purpose of this study is to evaluate the functional outcome, union and complication rates after surgical treatment of unstable or displaced proximal humeral fractures using the Polarus intramedullary nail, by reviewing our institutional experience and the relevant current literature.
Twenty-seven patients were treated operatively for proximal humeral fracture using the Polarus nail. Fractures were classified according to Neer’s classification. A number of parameters including patient demographics, mechanism of injury, operative time, time to union and complications were recorded. Functional outcome was evaluated using the Constant Shoulder Score. A comparison among functional outcomes in patients >60 years in relation to the younger ones was performed. Moreover, a review of the literature was carried out to evaluate the overall union and complication rates.
Two patients lost to follow-up were excluded from the analysis. For the twenty-five patients (mean age: 61 years), the mean follow-up was 36 months. There were 7 complications (28%), including one fixation failure, four protruded screws, one superficial infection and one case of impingement. The union rate was 96% (mean time to union: 4.2 months). The mean Constant score was 74.5 (range: 48–89). Patients under the age of 60 had a better functional outcome compared to patients >60 years of age (p<0.05). From the literature review and from a total of 215 patients treated with a Polarus nail, the mean union rate was 95.8%, the overall reported complication rate, including both minor and major complications, ranged widely from 9.3% up to 70%.
The Polarus nail was found to be an effective implant for stabilisation of proximal humeral fractures. Functional outcome is for the vast majority of the cases excellent or good, but in elderly patients a lower Constant score can be expected.
PMCID: PMC3554551  PMID: 23253302
Proximal humeral fractures; Polarus nail; Union; Complications; Functional outcome
15.  The role of stem cells in fracture healing and nonunion 
International Orthopaedics  2011;35(11):1587-1597.
Nonunion and large bone defects present a therapeutic challenge to the surgeon and are often associated with significant morbidity. These defects are expensive to both the health care system and society. However, several surgical procedures have been developed to maximise patient satisfaction and minimise health-care-associated and socioeconomic costs. Integrating recent evidence into the diamond concept leads to one simple conclusion that not only provides us with answers to the “open questions” but also simplifies our entire understanding of bone healing. It has been shown that a combination of neo-osteogenesis and neovascularisation will restore tissue deficits, and that the optimal approach includes a biomaterial scaffold, cell biology techniques, a growth factor and optimisation of the mechanical environment. Further prospective, controlled, randomised clinical studies will determine the effectiveness and economic benefits of treatment with mesenchymal stem cells, not in comparison to other conventional surgical approaches but in direct conjunction with them.
PMCID: PMC3193959  PMID: 21863226
16.  Effects of Antithrombotic Drugs Fondaparinux and Tinzaparin on In Vitro Proliferation and Osteogenic and Chondrogenic Differentiation of Bone-Derived Mesenchymal Stem Cells 
Journal of Orthopaedic Research  2011;29(9):1327-1335.
An unexpected side effect of some classes of anticoagulants has been osteoporosis which may be, at least in part, related to deranged mesenchymal stem cell (MSC) function. The aim of the present study was to compare the effect of fondaparinux (FDP), a novel antithrombotic with a traditional widely used low molecular weight heparin, tinzaparin (TZP) on MSC proliferation and differentiation. MSCs were isolated from trabecular bone of 14 trauma patients by a collagenase-based digestion procedure and expanded in standard conditions until passage 3. Proliferation and differentiation of MSCs to chondrocytes and osteoblasts was assessed with or without the addition of FDP and TZP using standard in vitro assays and a broad range of drug concentrations. Flow cytometry was used for MSC phenotyping. In the age studied group (17–74 years old) the MSC frequency in collagenase-released fractions was 641/106 cells (range 110–2,158) and their growth characteristics were ∼4 days/population doubling. Cultures had a standard MSC phenotype (CD73+, CD105+, CD146+, CD106+, and CD166+). Cell proliferation was assessed by both colony-forming unit-fibroblast (CFU-F) and colorimetric tetrazolium salt XTT assays. In both assays, MSC proliferation was inhibited by the addition of TZP, particularly at high concentrations. In contrast, FDP had no effect on MSC proliferation. Osteogenic differentiation and chondrogenic differentiation were not affected by the addition of either TZP or FDP. Whilst MSC proliferation, but not differentiation, is negatively affected by TZP, there was no evidence for adverse effects of FDP in this in vitro model system which argues well for its use in the orthopedic setting. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1327–1335, 2011
PMCID: PMC3193377  PMID: 21432897
low molecular heparins; bone healing; MSC; chemical thromboprophylaxis
17.  Central and peripheral venous lines-associated blood stream infections in the critically ill surgical patients 
Critically ill surgical patients are always at increased risk of actual or potentially life-threatening health complications. Central/peripheral venous lines form a key part of their care. We review the current evidence on incidence of central and peripheral venous catheter-related bloodstream infections in critically ill surgical patients, and outline pathways for prevention and intervention. An extensive systematic electronic search was carried out on the relevant databases. Articles were considered suitable for inclusion if they investigated catheter colonisation and catheter-related bloodstream infection. Two independent reviewers engaged in selecting the appropriate articles in line with our protocol retrieved 8 articles published from 1999 to 2011. Outcomes on CVC colonisation and infections were investigated in six studies; four of which were prospective cohort studies, one prospective longitudinal study and one retrospective cohort study. Outcomes relating only to PICCs were reported in one prospective randomised trial. We identified only one study that compared CVC- and PICC-related complications in surgical intensive care units. Although our search protocol may not have yielded an exhaustive list we have identified a key deficiency in the literature, namely a paucity of studies investigating the incidence of CVC- and PICC-related bloodstream infection in exclusively critically ill surgical populations. In summary, the diverse definitions for the diagnosis of central and peripheral venous catheter-related bloodstream infections along with the vastly different sample size and extremely small PICC population size has, predictably, yielded inconsistent findings. Our current understanding is still limited; the studies we have identified do point us towards some tentative understanding that the CVC/PICC performance remains inconclusive.
PMCID: PMC3487751  PMID: 22947496
18.  Angiographic embolisation of pelvic ring injuries. Treatment algorithm and review of the literature 
International Orthopaedics  2011;35(9):1381-1390.
The purpose of this study was to evaluate the relation between pelvic fracture patterns and the angiographic findings, and to assess the effectiveness of the embolisation.
This retrospective study, included patients with pelvic fractures and angiographic evaluation. Demographics, Injury Severity Score (ISS), associated injuries, embolisation time, blood units needed, method of treatment and complications were recorded and analysed. Fractures were classified according to the Burgess system.
Between 1998 and 2008, 34 patients with pelvic fractures underwent angiographic investigation. Twenty six were males. The mean age was 41 years. Twenty-seven were motor vehicle accidents and seven were falls. There were 11 anterior posterior (APC) fractures, 12 lateral compression (LC), eight vertical shear (VS) patterns and three with combined mechanical injuries. The median ISS was 33.1 (range 5–66). From the 34 who underwent angiography, 29 had positive vascular extravasations. From them, 21 had embolisation alone, two had vascular repair and embolisation, five required vascular repair alone and one patient died while being prepared for embolisation. Five cases were re-embolised. The findings suggested that AP fractures have a higher tendency to bleeding compared with LC fractures. Both had a higher chance of blood loss compared to VS and complex fracture patterns. We reported 57 additional injuries and 65 fractures. The complications were: one non lethal pulmonary embolism, one renal failure, one liver failure, one systemic infection, two deep infections and two psychological disorientations. Seven patients died in hospital.
Control of pelvic fracture bleeding is based on the multidisciplinary approach mainly related to hospital facilities and medical personnel’s awareness. The morphology of the fracture did not have a predictive value of the vascular lesion and the respective bleeding.
PMCID: PMC3167455  PMID: 21584644
19.  Proximal tibial fractures: early experience using polyaxial locking-plate technology 
International Orthopaedics  2010;35(8):1215-1221.
Between 2004 and 2009, 60 patients with proximal tibial fractures were included in this prospective study. All fractures were treated with the polyaxial locked-plate fixation system (DePuy, Warsaw, IN, USA). Clinical and radiographic data, including fracture pattern, changes in alignment, local and systemic complications, hardware failure and fracture union were analysed. The mean follow-up was 14 (12–36) months. According to the Orthopaedic Trauma Association (OTA) classification, there were five 41-A, 28 41-B and 27 41-C fractures. Fractures were treated percutaneously in 30% of cases. Double-plating was used in 11 cases. All but three fractures progressed to union at a mean of 3.2 (2.5–5) months. There was no evidence of varus collapse as a result of polyaxial screw failure. No plate fractured, and no screw cut out was noted. There was one case of lateral joint collapse (>10°) in a patient with open bicondylar plateau fracture. The mean Knee Society Score at the time of final follow-up was 91 points, and the mean functional score was 89 points. The polyaxial locking-plate system provided stable fixation of extra-articular and intra-articular proximal tibial fractures and good functional outcomes with a low complication rate.
PMCID: PMC3167437  PMID: 21107983
20.  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
21.  Reamer-irrigator-aspirator indications and clinical results: a systematic review 
International Orthopaedics  2011;35(7):951-956.
The ‘reamer-irrigator-aspirator’ (RIA) is an innovation developed to reduce fat embolism (FE) and thermal necrosis (TN) that can occur during reaming/nailing of long-bone fractures. Since its inception its indications have expanded to include the treatment of long-bone osteomyelitis and as a harvester of bone graft/mesenchymal stem cells (MSCs).
This study involved a systematic review, via Pubmed® and Google Scholar®, of English language sources (nine non-clinical studies, seven clinical studies and seven case reports) using the keywords: ‘reamer’, ‘irrigator’, ‘aspirator’ (1st May 2010). Sources were reviewed with reference to the RIAs efficacy in (1) preventing FE/TN, (2) treating long-bone osteomyelitis, (3) harvesting bone graft/MSCs, and (4) operating safely. Experimental data supports the use of the RIA in preventing FE and TN, however, there is a paucity of clinical data.
The RIA is a reliable method in achieving high volumes of bone graft/MSCs, and high union rates are reported when using RIA bone-fragments to treat non-unions. Evidence suggests possible effectiveness in treating long-bone osteomyelitis. The RIA appears relatively safe, with a low rate of morbidity provided a meticulous technique is used. When complications occur they respond well to conventional techniques. The RIA demands further investigation especially with respect to the optimal application of MSCs for bone repair strategies.
PMCID: PMC3167404  PMID: 21243358
22.  Spinal metastasis in thyroid cancer 
Head & Neck Oncology  2012;4:39.
Thyroid carcinoma generally responds well to treatment and spinal metastasis is an uncommon feature. Many studies have looked at the management of spinal metastasis and proposed treatments, plans and algorithms. These range from well-established methods to potentially novel alternatives including bisphosphonates and vascular endothelial growth factor (VEGF) therapy, amongst others.
The purposes of this systematic review of the literature are twofold. Firstly we sought to analyse the proposed management options in the literature. Then, secondly, we endeavoured to make recommendations that might improve the prognosis of patients with spinal metastasis from thyroid carcinomas.
We conducted an extensive electronic literature review regarding the management of spinal metastasis of thyroid cancer.
We found that there is a tangible lack of studies specifically analysing the management of spinal metastasis in thyroid cancer. Our results show that there are palliative and curative options in the management of spinal metastasis, in the forms of radioiodine ablation, surgery, selective embolisation, bisphosphonates and more recently the VEGF receptor targets.
The management of spinal metastasis from thyroid cancer should be multi-disciplinary. There is an absence; it seems, of a definitive protocol for treatment. Research shows increased survival with 131I avidity and complete bone metastasis resection. Early detection and treatment therefore are crucial. Studies suggest in those patients below the age of 45 years that treatment should be aggressive, and aim for cure. In those patients in whom curative treatment is not an option, palliative treatments are available.
PMCID: PMC3466148  PMID: 22730910
23.  Analysis of the compatibility of dental implant systems in fibula free flap reconstruction 
Head & Neck Oncology  2012;4:37.
As a result of major ablative surgery, head and neck oncology patients can be left with significant defects in the orofacial region. The resultant defect raises the need for advanced reconstruction techniques. The reconstruction in this region is aimed at restoring function and facial contour. The use of vascularised free flaps has revolutionised the reconstruction in the head and neck. Advances in reconstruction techniques have resulted in continuous improvement of oral rehabilitation. For example, endosteal implants are being used to restore the masticatory function by the way of prosthetic replacement of the dentition. Implant rehabilitation usually leads to improved facial appearance, function, restoration of speech and mastication. Suitable dental implant placement’s site requires satisfactory width, height and quality of bone. Reconstruction of hard tissue defects therefore will need to be tailored to meet the needs for implant placement.
The aim of this feasibility study was to assess the compatibility of five standard commercially available dental implant systems (Biomet 3i, Nobel Biocare, Astra tech, Straumann and Ankylos) for placement into vascularised fibula graft during the reconstruction of oromandibular region.
Radiographs (2D) of the lower extremities from 142 patients in the archives of the Department of Radiology in University College London Hospitals (UCLH) were analysed in this study. These radiographs were from 61 females and 81 males. Additionally, 60 unsexed dry fibular bones, 30 right sided, acquired from the collection of the Department of Anatomy, University College London (UCL) were also measured to account for the 3D factor.
In the right fibula (dry bone), 90% of the samples measured had a width of 13.1 mm. While in the left fibula (dry bone), 90% of the samples measured had a width of 13.3 mm. Fibulas measured on radiographs had a width of 14.3 mm in 90% of the samples. The length ranges of the dental implants used in this study were: 7-13 mm (Biomet 3i), 10-13 mm (Nobel biocare), 8-13 mm (Astra Tech), 8-12 mm (Straumann ) and 8-11 mm (Ankylos).
This study reached a conclusion that the width of fibula is sufficient for placement of most frequently used dental implants for oral rehabilitation after mandibular reconstructive procedures.
PMCID: PMC3448503  PMID: 22721258
24.  The management of nonunion and delayed union of patella fractures: a systematic review of the literature 
International Orthopaedics  2010;35(6):791-795.
Nonunion and delayed union of patella fractures are rare conditions that are fraught with challenges. There exists limited evidence in the literature to guide the clinician in the management of these complications. Therefore, the purpose of this study was to perform a systematic review of the available evidence on the management of nonunion and delayed union of patella fractures. A total of five publications which met our criteria were identified and formed the basis of this study. The decision making in the treatment of this condition is based on the functional demands of the patient, the factors that led to the development of the nonunion, the potential impact of the biomechanical effects of a total patellectomy, and the presence of an intact extensor mechanism of the knee for a later reconstructive procedure. Patients with low functional demands may be managed with nonoperative methods; however, those who perform heavy physical work or participate in sports usually require open reduction and internal fixation. Tension band wiring is the treatment of choice for patients suitable for a reconstructive procedure. Partial or total patellectomy is also an option for small distal fragments or an inability to satisfactorily perform internal fixation.
PMCID: PMC3103972  PMID: 20680273
25.  Surgical treatment of coccygodynia: an analytic review of the literature 
European Spine Journal  2010;20(5):698-705.
Coccygodynia is a pathological condition associated with pain–discomfort all around the bottom end of the spine. The aetiology and the intensity of the symptoms may defer significantly. The effectiveness of the surgical treatment remains obscure. Our purpose, through this systematic review is to evaluate the results of surgical treatment of coccygectomy. Literature retrieval was performed by the use of the PubMed searching engine utilising the terms ‘coccygodynia–coccygectomy’ in the English language from January 1980 to January 2010. Case reports and tumour related case series were excluded as well as articles published in other languages. In total 24 manuscripts were analyzed. Only 2 of them were prospective studies whereas 22 were retrospective case series; five were classified as Level III studies and the remaining as Level IV studies. In total, 671 patients with coccygodynia underwent coccygectomy following failed conservative management. The sex ratio, male/female was 1:4.4. The most popular aetiology for coccygodynia was direct trauma in 270 patients. 504 of the patients reported an excellent/good outcome following the procedure. There were 9 deep and 47 superficial infections. Other complications included two haematomas, six delayed wound healings and nine wound dehiscence. The overall complication rate was 11%. Patients with history of spinal or rectal disorders, as well as idiopathic or with compensation issues, had less predictable outcome than those with history of trauma or childbirth. Coccygectomy can provide pain relief to as high as 85% of the cases. The most common reported complication was wound infection.
PMCID: PMC3082682  PMID: 21046173
Coccygodynia; Coccygectomy; Coccyx surgical treatment

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