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1.  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
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.  “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
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.  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.  Genetic predisposition to fracture non-union: a case control study of a preliminary single nucleotide polymorphisms analysis of the BMP pathway 
Despite the known multi-factorial nature of atrophic fracture non-unions, a possible genetic predisposition for the development of this complication after long bone fractures remains unknown. This pilot study aimed to address this issue by performing a preliminary SNP analysis of specific genes known to regulate fracture healing.
A total of fifteen SNPs within four genes of the Bone Morphogenetic Protein (BMP) pathway (BMP-2, BMP-7, NOGGIN and SMAD6) were examined, in 109 randomly selected patients with long bone fractures as a result of motor vehicle accident, fall or direct blow. There were sixty-two patients with atrophic non-union and forty-seven patients (54 fractures) with uneventful fracture union. Overall SNPs frequencies were computed with respect to patient's age, gender, smoking habits, fracture-associated parameters and the use of nonsteroidal anti-inflammatory drugs (NSAIDs), and tested for their association to the impaired bone healing process, using binary logistic regression (STATA 11.1; StataCorp, Texas USA).
Statistical analysis revealed age to be an important covariate in the development of atrophic non-union (p = 0.01, OR 1.05 [per year]), and two specific genotypes (G/G genotype of the rs1372857 SNP, located on NOGGIN and T/T genotype of the rs2053423 SNP, located on SMAD6) to be associated with a greater risk of fracture non-union (p = 0.02, OR 4.56 and p = 0.04, OR 10.27, respectively, after adjustment for age).
This is the first clinical study to investigate the potential existence of genetic susceptibility to fracture non-union. Even though no concrete conclusions can be obtained from this pilot study, our results indicate the existence of a potential genetically predetermined impairment within the BMP signalling cascade, initiated after a fracture and when combined with other risk factors could synergistically increase the susceptibility of a patient to develop non-union. Further research is desirable in order to clarify the genetic component and its role and interaction with other risk factors in the development of atrophic long bone non-union, as simple genetic testing may contribute to the early identification of patients at risk in the future and the on-time intervention at the biologic aspects of bone healing.
PMCID: PMC3053586  PMID: 21310029
8.  The Synergistic Effect of Autograft and BMP-7 in the Treatment of Atrophic Nonunions 
Combining autologous bone graft and recombinant human bone morphogenetic protein-7 (BMP-7) to treat long-bone fracture aseptic atrophic nonunions theoretically could promote bone healing at higher rates than each of these grafting agents separately. We retrospectively reviewed prospectively collected data on patient general characteristics, clinical outcomes, and complications over 3 years to determine the healing rates and the incidence of complications and adverse events of this “graft expansion rationale.” There were 45 patients (32 male) with a median age of 43 years (range, 19–76 years). Minimum followup was 12 months (mean, 24.5 months; range, 12–65 months). There were seven humeral, 19 femoral, and 19 tibial nonunions. The median number of prior operations was two (range, 1–7). All fractures united. Clinical and radiographic union occurred within a median of 5 months (range, 3–14 months) and 6 months (range, 4–16 months), respectively. Thirty-nine (87%) patients returned to their preinjury occupation at a mean of 4.2 months (range, 3–6 months). The median visual analog scale pain score was 0.9 (range, 0–2.8; maximum 10), and the median functional score was 86 (range, 67–95; maximum 100) at the final followup. BMP-7 as a bone-stimulating agent combined with conventional autograft resulted in a nonunion healing rate of 100% in these 45 patients.
Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.
PMCID: PMC2772926  PMID: 19396502

Results 1-8 (8)