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The systemic stimulation of mesenchymal stem cells (MSCs) in bone marrow in response to trauma
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Abstracts / Injury Extra 43 (2013) 71–127
from April 2003 to April 2007. Then we ascertained in-hospital mortality rates at 30 days and at one year following admission to hospital using Hospital Episode Statistics (HES). Unplanned hospital readmission rates for all causes (including episodes of thromboembolism and bleeding) within 30 days (all years) and one year (2003–2005) were also established. A total of 150 hospitals were contacted and data gathered from 62 hospitals (response rate 41.3%). There were 255,841 patients with neck of femur fractures during this five year period who were assessed for morbidity and mortality correlating it to the thromboprophylaxis policy. There was no significant difference in hospital readmission within 30 days or diagnosis of thromboembolism or haemorrhage among hospitals of different thromboprophylaxis policies. The hospitals using LMWH in half the dose recommended by the British National Formulary had significantly reduced mortality in-hospital (odds ratio (OR) 0.79, 95% CI 0.69–0.90, P = 0.0006), at 30 days (OR 0.8 (0.70–0.92), P = 0.001) and at one year (OR 0.89 (0.80–1.00), P = 0.050) compared with no policy. Our data suggest that the thromboprophylaxis regimen for patients with fracture neck of femur should be half dose LMWH for the duration of the hospital stay. http://dx.doi.org/10.1016/j.injury.2012.07.201 [1A.7] Incidence of heterotopic ossification in acetabular fractures operated through a Kocher–Langenbeck approach K.K. Naikoti ∗ , A. Chitre, H. Wynnjones, N. Shah, A. Clayson Wrightington, Wigan and Leigh NHS Trust, United Kingdom Introduction: Heterotopic ossification is ectopic bone formation in soft tissues and is influenced by the severity of soft tissue damage either due to trauma or surgery. The reported incidence of Heterotopic ossification following fixation of acetabular fractures through Kocher–Langenbeck approach has been reported to be as high as 60% with severe Heterotopic ossification being as high as 20%. Aim: We report our results of using the Kocher–Langenbeck approach for fixation of acetabular fractures. Methods: 24 patients were identified from our operation database. Post-operative radiographs were reviewed retrospectively with a mean follow up of 11 months (range 6–20 months). Radiographs were graded using Brooker classification with grades 3–4 being classed as severe. All patients received continuous passive movement (CPM) in the immediate post-operative period and 6 weeks course of Indomethacin 25 mg thrice daily. Results: 4 (16.7%) patients developed heterotopic ossification, out of them significant heterotopic ossification was seen in 2 patients (8.3%). Conclusion: We believe a protocol using continuous passive movement of the affected limb and indomethacin may reduce the incidence of heterotopic ossification in patients undergoing acetabular fixation. http://dx.doi.org/10.1016/j.injury.2012.07.202
[1A.8] The systemic stimulation of mesenchymal stem cells (MSCs) in bone marrow in response to trauma H.B. Tan 1,∗ , E. Giannoudis 1
Jones 2 , K.
Henshaw 2 , D.
McGonagle 2 , P.V.
1
Academic Department of Trauma & Orthopaedics, Leeds General Infirmary, United Kingdom 2 Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, United Kingdom Summary: We investigated the dynamics of bone marrow mesenchymal stem cell stimulation and platelet-derived growth factor release following trauma. Introduction: Fracture healing represents a physiological process regulated by a variety of signalling molecules, growth factors and osteogenic progenitor cells. Bone healing following trauma is associated with increased serum concentrations of several pro-inflammatory and angiogenic growth factors. Platelet-derived growth factor (PDGF) has been shown to stimulate mesenchymal stem cell (MSC) proliferation in vitro. However, the in vivo relationship between the levels of PDGF and the numbers of MSCs in humans has not yet been explored. The aim of this study was to investigate PDGF release in the peripheral circulation following trauma and to correlate it with the numbers of MSCs in iliac crest bone marrow (BM) aspirate and in peripheral blood. Methods: Trauma patients with lower extremity fractures (n = 12, age 18–63 years) were recruited prospectively. Peripheral blood was obtained on admission, and at 1, 3, 5 and 7 days following admission. The serum was collected and PDGF was measured using the enzyme-linked immunosorbent assay (ELISA) technique. Iliac crest (BM) aspirate (20 ml) and peripheral blood (PB) (20 ml) was obtained on days 0–9 following admission. MSCs were enumerated using standard colonyforming unit fibroblasts (CFU-F) assay. Results: We observed a gradual increase in serum PDGF levels following fracture (r2 = 0.79, p = 0.005, n = 8), which reached up to 2-fold on day 7. In 5 out of 8 patients recruited for CFU-F study, an increase in iliac crest BM CFU-F per millilitre of aspirate was similarly observed, which reached an average 6-fold post-fracture (ranging from day 3 to day 9). No CFU-Fs were observed in PB at any time-point in all patients studied. In three patients, for which PDGF and CFU-F were measured in parallel, a strong positive correlation was observed between CFU-F numbers per millilitre of BM aspirate and circulating PDGF levels (r2 = 0.98, p < 0.01). Discussion and conclusion: Our data demonstrate, for the first time, that BM MSC pool in humans is not static and can be stimulated following trauma. This is not a result of mobilisation of MSCs into systemic circulation. Rather, MSC activation at remote sites, like iliac crest BM, can be due to systemic up-regulation of several cytokines and growth factors, including PDGF, in peripheral circulation. This data therefore enable a more comprehensive understanding of MSC dynamics in response to trauma and can inform the design of a clinical trial aimed to optimise the location and timing of BM harvest for use in bone regeneration following fracture. http://dx.doi.org/10.1016/j.injury.2012.07.203
Abstracts / Injury Extra 43 (2013) 71–127
from April 2003 to April 2007. Then we ascertained in-hospital mortality rates at 30 days and at one year following admission to hospital using Hospital Episode Statistics (HES). Unplanned hospital readmission rates for all causes (including episodes of thromboembolism and bleeding) within 30 days (all years) and one year (2003–2005) were also established. A total of 150 hospitals were contacted and data gathered from 62 hospitals (response rate 41.3%). There were 255,841 patients with neck of femur fractures during this five year period who were assessed for morbidity and mortality correlating it to the thromboprophylaxis policy. There was no significant difference in hospital readmission within 30 days or diagnosis of thromboembolism or haemorrhage among hospitals of different thromboprophylaxis policies. The hospitals using LMWH in half the dose recommended by the British National Formulary had significantly reduced mortality in-hospital (odds ratio (OR) 0.79, 95% CI 0.69–0.90, P = 0.0006), at 30 days (OR 0.8 (0.70–0.92), P = 0.001) and at one year (OR 0.89 (0.80–1.00), P = 0.050) compared with no policy. Our data suggest that the thromboprophylaxis regimen for patients with fracture neck of femur should be half dose LMWH for the duration of the hospital stay. http://dx.doi.org/10.1016/j.injury.2012.07.201 [1A.7] Incidence of heterotopic ossification in acetabular fractures operated through a Kocher–Langenbeck approach K.K. Naikoti ∗ , A. Chitre, H. Wynnjones, N. Shah, A. Clayson Wrightington, Wigan and Leigh NHS Trust, United Kingdom Introduction: Heterotopic ossification is ectopic bone formation in soft tissues and is influenced by the severity of soft tissue damage either due to trauma or surgery. The reported incidence of Heterotopic ossification following fixation of acetabular fractures through Kocher–Langenbeck approach has been reported to be as high as 60% with severe Heterotopic ossification being as high as 20%. Aim: We report our results of using the Kocher–Langenbeck approach for fixation of acetabular fractures. Methods: 24 patients were identified from our operation database. Post-operative radiographs were reviewed retrospectively with a mean follow up of 11 months (range 6–20 months). Radiographs were graded using Brooker classification with grades 3–4 being classed as severe. All patients received continuous passive movement (CPM) in the immediate post-operative period and 6 weeks course of Indomethacin 25 mg thrice daily. Results: 4 (16.7%) patients developed heterotopic ossification, out of them significant heterotopic ossification was seen in 2 patients (8.3%). Conclusion: We believe a protocol using continuous passive movement of the affected limb and indomethacin may reduce the incidence of heterotopic ossification in patients undergoing acetabular fixation. http://dx.doi.org/10.1016/j.injury.2012.07.202
[1A.8] The systemic stimulation of mesenchymal stem cells (MSCs) in bone marrow in response to trauma H.B. Tan 1,∗ , E. Giannoudis 1
Jones 2 , K.
Henshaw 2 , D.
McGonagle 2 , P.V.
1
Academic Department of Trauma & Orthopaedics, Leeds General Infirmary, United Kingdom 2 Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, United Kingdom Summary: We investigated the dynamics of bone marrow mesenchymal stem cell stimulation and platelet-derived growth factor release following trauma. Introduction: Fracture healing represents a physiological process regulated by a variety of signalling molecules, growth factors and osteogenic progenitor cells. Bone healing following trauma is associated with increased serum concentrations of several pro-inflammatory and angiogenic growth factors. Platelet-derived growth factor (PDGF) has been shown to stimulate mesenchymal stem cell (MSC) proliferation in vitro. However, the in vivo relationship between the levels of PDGF and the numbers of MSCs in humans has not yet been explored. The aim of this study was to investigate PDGF release in the peripheral circulation following trauma and to correlate it with the numbers of MSCs in iliac crest bone marrow (BM) aspirate and in peripheral blood. Methods: Trauma patients with lower extremity fractures (n = 12, age 18–63 years) were recruited prospectively. Peripheral blood was obtained on admission, and at 1, 3, 5 and 7 days following admission. The serum was collected and PDGF was measured using the enzyme-linked immunosorbent assay (ELISA) technique. Iliac crest (BM) aspirate (20 ml) and peripheral blood (PB) (20 ml) was obtained on days 0–9 following admission. MSCs were enumerated using standard colonyforming unit fibroblasts (CFU-F) assay. Results: We observed a gradual increase in serum PDGF levels following fracture (r2 = 0.79, p = 0.005, n = 8), which reached up to 2-fold on day 7. In 5 out of 8 patients recruited for CFU-F study, an increase in iliac crest BM CFU-F per millilitre of aspirate was similarly observed, which reached an average 6-fold post-fracture (ranging from day 3 to day 9). No CFU-Fs were observed in PB at any time-point in all patients studied. In three patients, for which PDGF and CFU-F were measured in parallel, a strong positive correlation was observed between CFU-F numbers per millilitre of BM aspirate and circulating PDGF levels (r2 = 0.98, p < 0.01). Discussion and conclusion: Our data demonstrate, for the first time, that BM MSC pool in humans is not static and can be stimulated following trauma. This is not a result of mobilisation of MSCs into systemic circulation. Rather, MSC activation at remote sites, like iliac crest BM, can be due to systemic up-regulation of several cytokines and growth factors, including PDGF, in peripheral circulation. This data therefore enable a more comprehensive understanding of MSC dynamics in response to trauma and can inform the design of a clinical trial aimed to optimise the location and timing of BM harvest for use in bone regeneration following fracture. http://dx.doi.org/10.1016/j.injury.2012.07.203