Pharmacological adjuncts to stop bleeding: options and effectiveness.

Severe trauma and massive haemorrhage represent the leading cause of death and disability in patients under the age of 45 years in the developed world. Even though much advancement has been made in our understanding of the pathophysiology and management of trauma, outcomes from massive haemorrhage remain poor. This can be partially explained by the development of coagulopathy, acidosis and hypothermia, a pathological process collectively known as the "lethal triad" of trauma. A number of pharmacological adjuncts have been utilised to stop bleeding, with a wide variation in the safety and efficacy profiles. Antifibrinolytic agents in particular, act by inhibiting the conversion of plasminogen to plasmin, therefore decreasing the degree of fibrinolysis. Tranexamic acid, the most commonly used antifibrinolytic agent, has been successfully incorporated into most trauma management protocols effectively reducing mortality and morbidity following trauma. In this review, we discuss the current literature with regard to the management of haemorrhage following trauma, with a special reference to the use of pharmacological adjuncts. Novel insights, concepts and treatment modalities are also discussed.

Mesenchymal Stem Cell physiology can be affected by antibiotics: An in vitro study.

The aim of this study was to investigate the effect of antibiotics used in clinical practice on Mesenchymal Stem Cells (MSCs) potential to proliferate and differentiate towards an osteogenic lineage. Trabecular bone was obtained from 10 patients (mean age of 36 years, range 18-72) suffering from long bone fractures. Mesenchymal Stem Cells (MSCs) were isolated and functional assays on their proliferation (CFU-F and XTT) and osteogenic differentiation (alkaline phosphatase activity and total calcium production) were performed. The effect of medium supplementation with gentamicin, vancomycin, benzyl-penicillin, flucloxacillin, cefuroxime and metronidazole was analysed. In concentrations found in peripheral circulation, none of the studies antibiotics had an effect on MSCs ability to proliferate and differentiate towards osteogenic lineage. Vancomycin and gentamicin in concentrations of 200 µg/ml and 75 µg/ml respectively, down-regulated the proliferation and osteogenic activity of MSCs. Some combination of the studied antibiotics found to inhibit both proliferation and osteogenesis. High antibiotic concentrations and the combination of different formulations can have detrimental effects on osteoprogenitor cells physiology and potentially bone healing.

Fracture non-union: Can biomarkers predict outcome?

Delayed bone healing and non-union occurs in approximately 10-15% of long bone fractures. Both pathologies may result in prolonged period of pain, disability and repetitive operative interventions. Despite intense investigations and progress done in understanding the pathophysiologic processes governing bone healing, the diagnostic tools have not been altered. The clinical findings and radiographic features remain the two important landmarks of diagnosing non-union and even when the diagnosis is established there is debate on the ideal timing and mode of intervention. Emerging evidence suggest that there are certain molecules and genes that can serve as predictors of potentially unsuccessful fracture union. This article summarises the current evidence on the available 'bio-markers'to predict fracture non-union.

Prevalence of ocular and orbital injuries in polytrauma patients.

INTRODUCTION: Polytrauma patients usually suffer from both life-threatening injuries, where early intervention is mandatory in order to prevent mortality from uncontrollable haemorrhage-especially during the "golden hour", and secondary injuries of lower priority which receive delayed referral or treatment. Non-life-threatening injuries can sometimes be overlooked and so remain untreated until a much later stage. The aim of this study was to investigate the incidence of eye (ocular and orbital) injuries in polytrauma (injury severity score >15) patients and describe their complexities and outcomes. MATERIALS AND METHODS: Over a 10-year period (1991-2001), all polytrauma patients admitted in our institution were evaluated. Patients with ocular and orbital injuries were identified and their records were retrospectively analyzed. RESULTS: Out of a total of 2,985 polytrauma patients, 222 (7.5%) met the inclusion criteria. Forty-one case notes were not retraceable. The files of 181 patients were therefore available for review. The mean age of this group of patients was 33 years (3-84) with a sex ratio (male: female ratio) 5:1. The types of eye injuries encountered were orbital wall fractures (61%), periorbital swelling or hematoma (46%), sub-conjunctival hemorrhage (23%), periorbital lacerations (22%), optic nerve trauma (11%) and penetrating eye injuries (6%). Visual impairment resulted in about 67% of survivors, including loss of eye in 24%. Diplopia requiring intervention was seen in 24% of the cases. CONCLUSIONS: Polytrauma patients are at high risk for vision-threatening injuries, and an early multidisciplinary approach is essential for early detection and treatment.

The effect of autologous serum obtained after fracture on the proliferation and osteogenic differentiation of mesenchymal stem cells.

The purpose of this study was to investigate the potential of Mesenchymal Stem Cells (MSCs) obtained from patients suffering from fractures to proliferate and differentiate towards osteogenic lineage with the use of autologous serum. In addition the effect of medium supplementation with the use of autologous serum obtained at different time points (patients' admission, first, third and seventh post-operative day) was investigated. In total eight patients suffering from lower limb long bone fractures with mean age of 39 (range 22-68 years) were included in this study. MSCs were isolated and cultivated in 10% of either Fetal Calf Serum (FCS) or autologous serum. Cellular proliferation was examined by XTT assay and Vybrant assay. The osteogenic differentiation was assessed by total calcium production and alkaline phosphatase production. Cellular proliferation and osteogenic differentiation was significantly statistically higher in patients' serum obtained on admission than in FCS. A negative effect on proliferation was noted with serum obtained on the first postoperative day. Subsequently, both proliferation and differentiation were gradually increased with autologous serum collected during the 3rd and 7th postoperatively days. Autologous serum obtained after fracture is superior in terms of proliferation and osteogenic differentiation to the currently used FCS. Surgery seems to have a negative effect on the quality of serum. These findings should be considered in cases where ex-vivo expansion of MSCs is needed. Recuperation of serum's quality takes place at a later time point within the first weeks after fracture.