Docking site interventions following bone transport using external fixation: a systematic review of the literature.

PURPOSE: Although bone transport is a well-recognised technique to address segmental bone defects, optimal management of docking sites is not absolutely determined. Some surgeons routinely intervene in all cases, and others prefer to observe and intervene only if spontaneous union does not occur. Primary aim of the study was to compare rates of docking site union between patients who underwent routine docking site intervention and those who did not. METHODS: A systematic literature review using the keywords "bone transport", "docking", "tibia", and "femur" was performed in PubMed using PRISMA guidelines. Studies published in English from January 2000 to August 2022 were included and assessed independently by two reviewers. Pooled analysis was undertaken dividing patients into two groups: those managed by routine intervention and those initially observed. RESULTS: Twenty-three clinical studies met the eligibility criteria for pooled analysis, including 1153 patients, 407 in the routine intervention and 746 in the observed group. The rate of union after initial treatment was 90% in the routine intervention group and 66% in the observed group (p < 0.0001). Overall union rates at the end of treatment were similar at 99% in both groups. Patients in the observed group required an average of 2.2 procedures to achieve union overall compared with 3.8 in the routine intervention group. Time in frame was similar between groups. CONCLUSION: Based on the current literature, routine docking site interventions cannot be recommended, since this may lead to unnecessary interventions in two thirds of patients. Timely selective intervention in those at high risk or after a defined period of observation would appear to be a logical approach.

Retrograde intramedullary nailing or locked plating for stabilisation of distal femoral fractures? A comparative study of 193 patients.

PURPOSE: The aim of this study was to evaluate the results of distal femoral fracture fixation of two different methods, lateral locking plate (LP) or an Intra-medullary nail (IMN), in patients managed in our institution. More specifically, to assess: (a) if there was a difference in functional outcomes between the LP and IMN groups; (b) whether the rate of complications was different between the two groups. METHODS: Between January 2009 and December 2018 adult patients with distal femoral fractures managed in our unit with either LP or IMN for extra and intra-articular fractures were eligible to participate. Demographic details, fracture type, procedures performed, time to union, complications and functional scores (Oxford Knee Score) were recorded and analysed. The mean follow up was 4 years (12-120 months). RESULTS: Out of 193 patients who met the inclusion criteria, 93 received an IMN whereas 100 patients were treated with LP. Mean age was 64.2 (18-99) and 70.1 (18-100) for the IMN and LP groups respectively. Overall, the two groups had similar demographics and there was no significant difference in the type of fractures sustained (p > 0.05). The Oxford Knee Score was highest for patients fixed with LP, mean 37.3 (6-48, SD 7.3) versus 28.4 (3-48, SD 14.4), (p = < 0.02) compared to the IMN group. In terms of complications, the rate of non-union was higher in the LP group 8.6% versus 4% in those patients treated with an IMN, p value < 0.01. CONCLUSION: While the rate of non-union was higher in the LP group and the functional results were superior in the plating group.

The in vitro effects of platelet products on the biophysiological functions of human bone marrow mesenchymal stromal cells: a systematic review.

Platelet products (PP) and bone-marrow aspirate are popular sources of osteoinductive signalling molecules and osteogenic bone marrow mesenchymal stromal cells (BM-MSCs) used in the treatment of impaired bone healing. However, the combined use of PP and BM-MSCs in clinical studies has reported mixed results. Understanding the cellular and molecular interactions between PP and BM-MSCs plays the important role of guiding future research and clinical application. This systematic review investigates the effects of PP on the biophysiological functions of BM-MSCs in in vitro human studies, including (i) proliferation, (ii) migration, (iii) differentiation, (iv) growth factor/cytokine/protein expression, (v) immunomodulation, (vi) chemotactic effect on haematopoietic stem cells, (vii) response to apoptotic stress, and (viii) gene expression. In vitro studies in human have demonstrated the multi-faceted 'priming effect' of PP on the biophysiological functions of BM-MSCs. PP has been shown to improve proliferation, migration, osteogenic differentiation, reaction to apoptotic stress as well as immunomodulatory, pro-angiogenic and pro-inflammatory capacities of BM-MSCs. Several factors are highlighted that restrict the transferability of these findings into clinical practice. Therefore, more collaborative in vitro research in humans modelled to reflect clinical practice is required to better understand the effects of PP exposure on the biophysiological function(s) of BM-MSCs in human.

Enrichment and preserved functionality of multipotential stromal cells in bone marrow concentrate processed by vertical centrifugation.

The concentration of bone marrow (BM) aspirate (BMA) is increasingly valued for bone and cartilage repair, particularly with the rarity and donor-variability of BM-multipotential stromal cells (BM-MSCs). The present study aimed to assess BM-MSC yield following BM concentration using a fast and compact-sized vertical centrifugation system. BMA concentrate (BMAC) was separated in a 1 min process and collected easily after an automatic discarding of plasma and red blood cells. A significant increase in CD45low CD271high cells per BMAC volume (measured using flow-cytometry) was noted (4-fold, p = 0.0001). Additionally, the vertical centrifugation system helped to enrich colony numbers (assessed by CFU-F assays) in BMAC comparably with conventional centrifugation systems, BioCUE™ and SmartPReP-2® (4.3-fold, 4.6-fold and 3-fold, respectively). Next, a functional assessment of BM-MSCs processed by vertical centrifugation was performed, and MSC viability and proliferation were not affected. Also, these BM-MSCs showed similar alkaline phosphatase and calcium levels to those of BMA-MSCs when osteogenically induced. Furthermore, glycosaminoglycans and Nile red levels in addition to the gene expression assays confirmed that there was no significant change in chondrogenic or adipogenic abilities between BMA-MSCs and BMAC-MSCs. The expression levels of selected angiogenic and immunomodulatory mediators were also similar between the two groups. Collectively, the vertical centrifugation system helped to enrich BM-MSCs effectively, while maintaining cell viability and functions. Thus, such a vertical centrifugation system for BM concentration can be valuable for various regenerative therapies.

A crosslinked collagen membrane versus a non-crosslinked bilayer collagen membrane for supporting osteogenic functions of human bone marrow-multipotent stromal cells.

Barrier membranes are popularly used for guided bone regeneration (GBR). However, more knowledge is needed to assess how these membranes could be of therapeutic value when populated with native multipotent stromal cells (MSCs), particularly in the orthopaedic field. The present manuscript investigated the activities of human bone marrow-multipotent stromal cells (BM-MSCs) when loaded on to two differently structured pure collagen membranes. A crosslinked collagen membrane (CS) was tested versus a non-crosslinked bilayer collagen membrane, Bio-Gide® (BG). Following loading with BM aspirate containing native MSCs, cell attachment to the membranes was examined using electron microscopy and flow cytometry. Furthermore, alkaline phosphatase (ALP) expression and calcium deposition levels were investigated for these BM-aspirate-loaded membranes. Culture-expanded BM-MSCs were also used to load membranes and confirm the MSC functional data. All membranes supported BM-MSC attachment. However, larger numbers of attached BM-MSCs were detected for CS as compared to BG (p = 0.0010). In osteogenic medium, ALP activity was higher for CS than BG (p = 0.0312). Total calcium deposition (not normalised to cell count) was also higher for CS than BG (p = 0.0073). Consistently, the normalised secreted vascular endothelial growth factor A (VEGF-A) levels were higher in BM-MSCs loaded on CS relative to BG (p = 0.0302). Collectively, both collagen membranes supported the osteogenic functions of BM-MSCs. However, CS was found to be overall superior probably since it provided more BM-MSC attachment. These collagen membranes could potentially be used to improve GBR outcomes in orthopaedic applications.

The effects of diabetes medications on post-operative long bone fracture healing.

PURPOSE: Diabetes has long been known to have an impact on bone repair. More recently, however, most diabetic patients receive medications to normalise this hyperglycaemic environment. To date, no studies have investigated the effects of diabetic medications on fracture healing in humans. METHOD: Patients were identified from two tertiary trauma centres. Inclusion criteria were adult patients having sustained a closed diaphyseal femoral or tibial fracture, treated surgically. Exclusion criteria were open, pathological or peri-prosthetic fractures, and patients having sustained polytrauma. Matched non-diabetic controls were identified, matched for age, sex, fracture classification and osteosynthesis. Output measures were: time to callus first appearance, bridging of involved cortices and time to union, along with the eventual outcome: union/non-union. RESULTS: A total of 36 (25 males) eligible patients were identified with a control group of 166 patients (138 males). ANOVA demonstrated class of medication to have a significant effect at two of the three time points and on the eventual outcome. Multiple regression analysis also demonstrated significant impact (p = 0.02). CONCLUSION: All classes of medication demonstrated anti-osteogenic effects compared to the control cohort. Biguanides demonstrated this in contrast to the in vitro evidence to date. Sulphonylureas demonstrated this to a greater extent; however, no in vitro evidence is available for comparison within this class. Clinicians should be aware of these delays in bone healing when treating diabetic patients and aim for optimal blood glucose control until such time as further research can be undertaken.

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.

Are intra-articular injections of Hylan G-F 20 efficacious in painful osteoarthritis of the knee? A systematic review & meta-analysis.

AIM: To systematically review evidence and perform a meta-analysis of the efficacy of intra-articular (IA) injections of Hylan G-F 20 for the treatment of painful osteoarthritis (OA) of the knee. METHODS: Systematic review of the Embase and PubMed databases up to July 2013 of randomised placebo-controlled trials studying the effect of Hylan G-F 20 in patients with painful knee OA, with a meta-analysis of trials reporting visual analogue scores (VAS) for weight-bearing pain in the knees of patients followed up for a minimum of 6 months. RESULTS: Six placebo-controlled randomised trials were identified on systematic review of which two studies met criteria for inclusion in the meta-analysis. Meta-analysis demonstrated that at 6-month follow up, there was no significant difference between Hylan G-F 20 and control in terms of reduction in VAS for weight bearing pain. (Mean Difference - 12.96 (95% CI: -35.48, 9.56). Z tests used to test for overall effect showed that the difference between the two groups was not significant (p = 0.26). DISCUSSION: A significant placebo effect exists for patients receiving IA injections for the treatment of painful knee OA. The withdrawal of fluid from the affected knee prior to any injectable therapy may itself have additional benefits which in isolation have not been studied. This may form the basis of future research. The authors' acknowledge that although limited conclusions can be drawn from the results of this study, the meta-analysis presented has not been performed previously and will further contribute to the knowledge on this subject. CONCLUSION: Although Hylan G-F 20 may produce improvement in VAS scores for weight-bearing pain at 6-month follow up in OA knees treated with it, patients should be informed that this may be equivalent to that seen with control treatments.

The impact of traumatic pelvic fractures on sporting activity and quality of life.

BACKGROUND: Pelvic fractures (PFX) reflect high-energy trauma with high mortality and morbidity. AIM: We attempted to determine: whether there is a decrease in levels of sporting and physical activity in patients with operatively-treated PFX; risk factors for decreased sporting activity; any correlation between sporting activity and quality of life in this group. METHODS: Retrospective demographics on mechanism of injury, fracture type, associated injury and injury severity score, as well as prospective documentation of the level and frequency of sporting activity, were collected from adult patients treated operatively for a PFX between 2007 and 2010, using a specifically designed questionnaire. Quality of life before and after injury was also recorded using the EuroQol-5D health-outcome tool. RESULTS: 80 patients without pre-existing musculoskeletal disability were enrolled. The mean age was 44.9 years (18-65). The mean follow-up was 30.5 months (12-39). A decrease in level and frequency of sporting activity was observed. It was associated with lower-extremity associated injuries, but not with injury severity score, PFX severity, PFX type, age, or timing of follow-up. Sporting activity before injury predicted higher levels of sporting participation after injury. Decreased sporting activity after injury was associated with decreased EuroQol-SD score. CONCLUSIONS: Patients should be counselled on the likelihood of a reduction in sporting activities after surgically treated PFX. A larger multi-centre study is needed to further expand on the evidence of the true impact of PFX and its associated injuries on sporting activity.

Partial anterior sacrectomy with nerve preservation to treat locally advanced rectal cancer.

AIM: Most studies that have reported outcomes after composite abdomino-sacral resection for locally advanced/recurrent rectal cancer have involved resections below the S2/3 disc space. Involvement of the sacrum above this level is uncommon and, until recently, was considered a contraindication to resection. METHOD: We report here a surgical technique to deal with high sacral involvement with an anterior approach and maintenance of sacropelvic stability. RESULTS: The operative findings confirmed a locally perforated rectal cancer with an associated abscess cavity and direct invasion into S2. Given the likelihood that a complete dislocation of the sacrum would cause significant neurological damage and pelvic instability without oncological benefit, we opted for a partial high anterior sacrectomy with nerve preservation. The patient made an uncomplicated recovery without neurological deficit and was able to walk with the aid of crutches from postoperative day 3. CONCLUSION: While a high sacral transection is appropriate for some patients with locally advanced/recurrent rectal cancer, operative decisions and options should be tailored to each individual.

Stabilisation of AO OTA 31-A unstable proximal femoral fractures: Does the choice of intramedullary nail affect the incidence of post-operative complications? A systematic literature review and meta-analysis.

OBJECTIVE: To determine if there was a difference in the risk of post-operative complications associated with the use of different intramedullary (IM) devices in the treatment of unstable AO OTA 31-A trochanteric fractures. DESIGN: Systematic literature review and meta-analysis. METHODS: A systematic literature review was carried out in January 2022 in the Embase, MEDLINE and Cochrane databases. Studies comparing INTERTAN™ to other intramedullary nails for the treatment of AO OTA 31-A trochanteric fractures were selected for inclusion. After data extraction, meta-analyses were carried out on postoperative outcomes, with specific focus placed on unstable fracture patterns. RESULTS: Twenty-three studies were suitable for inclusion, of which seventeen reported on outcomes in unstable fractures. INTERTAN reduced the risk of revision/reoperation by 64% (RR 0.36, 95% CI 0.25 to 0.54, p <0.0001), implant failures by 62% (RR 0.38, 95% CI 0.25 to 0.57, p<0.0001) and hip and thigh pain by 50% (RR 0.50, 95% CI 0.35 to 0.71, p=0.0001) in unstable fractures. No differences were noted between IM nail designs for infection rates, healing time, non-union rates, femoral shortening, or Harris Hip Score. CONCLUSIONS: The INTERTAN IM nail may reduce incidence of implant-related complications, hip and thigh pain, and the need for revision/reoperation without compromising clinical and functional outcomes.

The management of post-traumatic osteoarthritis.

Posttraumatic arthritis primarily affects younger individuals, leading to reduced physical activity, chronic pain, and prolonged symptomatic treatments. The management of post-traumatic arthritis after fracture, dislocation or ligament rupture continues to be one of the most challenging clinical entities in orthopaedic and trauma surgery. Therapies to address early symptoms include anti-inflammatory agents, pain killers, corticosteroid or hyaluronic acid joint injections but these offer only temporary pain relief with hardly any mid or long term benefit. There are many surgical options for the treatment of posttraumatic arthritis. For the early stages, arthroscopic debridement should be considered. At late stages, corrective osteotomies or arthrodesis are strongly recommended for the young patients. In older patients arthroplasties remain the treatment of choice.

Use of antibiotic coated intramedullary nails in open tibia fractures: A European medical resource use and cost-effectiveness analysis.

PURPOSE: In patients with open tibial fractures, bone and wound infections are associated with an increased hospital length of stay and higher costs. The infection risk increases with the use of implants. Innovations to reduce this risk include antibiotic-coated implants. This study models whether the use of a gentamicin-coated intramedullary tibial nail is cost-effective for trauma centers managing patients with a high risk of infection. EFFICACY: Absolute infection risk and relative risk reduction, by fracture grade, for antibiotic-coated nails compared to standard nails for patients with open tibial fractures were estimated based on the results of a meta-analysis, which assessed the additional benefit of locally-administered prophylactic antibiotics in open tibia fractures treated with implants. The observed efficacy of antibiotic-coated nails in reducing infections was applied in an economic model. METHODS: The model compared infection rates, inpatient days, theatre usage and costs in high risk patients, with a Gustilo-Anderson (GA) grade III open fracture, for two patient cohorts from a trauma center perspective, with a 1-year time horizon. In one cohort all GAIII patients received a gentamicin-coated nail whilst GAI and GAII patients received a standard nail. All patients in the comparator cohort received a standard nail. Four European trauma centers provided patient-level data (n=193) on inpatient days, procedures and related costs for patients with and without infections. RESULTS: Using the gentamicin-coated nail in patients at high risk of infection (GAIII) was associated with 75% lower rate of infection and cost savings (€477 - €3.263) for all included centers; the higher cost of the implant was offset by savings from fewer infections, inpatient days (-26%) and re-operations (-10%). This result was confirmed by extensive sensitivity analyses. CONCLUSIONS: Analyses demonstrated that infection rates and total costs for in-hospital treatment could be potentially reduced by 75% and up to 15% respectively, by using a gentamicin-coated nail in patients at high risk of infection. Fewer infections, reduced inpatient days and re-operations may be potentially associated with use of antibiotic-coated implants. Results are sensitive to the underlying infection risk, with greatest efficacy and cost-savings when the coated implant is used in high risk patients.

Regulation of Angiogenesis Discriminates Tissue Resident MSCs from Effective and Defective Osteogenic Environments.

BACKGROUND: The biological mechanisms that contribute to atrophic long bone non-union are poorly understood. Multipotential mesenchymal stromal cells (MSCs) are key contributors to bone formation and are recognised as important mediators of blood vessel formation. This study examines the role of MSCs in tissue formation at the site of atrophic non-union. MATERIALS AND METHODS: Tissue and MSCs from non-union sites (n = 20) and induced periosteal (IP) membrane formed following the Masquelet bone reconstruction technique (n = 15) or bone marrow (n = 8) were compared. MSC content, differentiation, and influence on angiogenesis were measured in vitro. Cell content and vasculature measurements were performed by flow cytometry and histology, and gene expression was measured by quantitative polymerase chain reaction (qPCR). RESULTS: MSCs from non-union sites had comparable differentiation potential to bone marrow MSCs. Compared with induced periosteum, non-union tissue contained similar proportion of colony-forming cells, but a greater proportion of pericytes (p = 0.036), and endothelial cells (p = 0.016) and blood vessels were more numerous (p = 0.001) with smaller luminal diameter (p = 0.046). MSCs showed marked differences in angiogenic transcripts depending on the source, and those from induced periosteum, but not non-union tissue, inhibited early stages of in vitro angiogenesis. CONCLUSIONS: In vitro, non-union site derived MSCs have no impairment of differentiation capacity, but they differ from IP-derived MSCs in mediating angiogenesis. Local MSCs may thus be strongly implicated in the formation of the immature vascular network at the non-union site. Attention should be given to their angiogenic support profile when selecting MSCs for regenerative therapy.

Pelvic ring disruptions: treatment modalities and analysis of outcomes.

A systematic review of the English literature over the last 30 years was conducted in order to investigate the correlation of the clinical outcome of different types of pelvic ring injuries to the method of treatment. Three basic therapeutic approaches were analysed: non-operative treatment (group A), stabilisation of anterior pelvis (group B) and internal fixation of posterior pelvis (group C). Of 818 retrieved reports, 27 case series, with 28 groups of patients and 1,641 patients, met our inclusion criteria. The quality of the literature was evaluated using a structured questionnaire. Outcomes of the eligible studies were summarised by the medians of the reported results. Most of the component studies were of fair or poor quality. Certain radiological results (quality of reduction, malunion rates) were significantly better in group C. From the functional point of view only walking capacity was proved to be significantly better in the groups of operative treatment compared to the non-operative group.

A cost analysis of treatment of tibial fracture nonunion by bone grafting or bone morphogenetic protein-7.

The parameter of health economics in the use of any contemporary medical module plays a dominant role in decision making. A prospective nonrandomised comparative study of the direct medical costs on the first attempt of treating aseptic nonunions of tibial fractures, with either autologous-iliac-crest-bone-graft (ICBG) or bone morphogenetic protein-7 (BMP-7), is presented. Twenty-seven consecutive patients, who were successfully treated for fracture nonunions, were divided into two groups. Group 1 (n = 12) received ICBG and group 2 (n = 15) received BMP-7. All patients healed their nonunions, and the financial analysis presented represents a best-case scenario. Three out of 12 of the ICBG group required revision surgery while just one out of 15 required it in the BMP-7 group. Average hospital stay was 10.66 vs. 8.66 days, time-to-union 6.9 vs. 5.5 months, hospitals costs pound2,133.6 vs. pound1,733.33, and theatre costs were pound2,413.3 vs. pound906.67 for the ICBG and BMP-7 groups, respectively. The BMP-7 cost was pound3002.2. Fixation-implant was pound696.4 vs. pound592.3, radiology pound570 vs. pound270, outpatient pound495.8 vs. pound223.33, and other costs were pound451.6 vs. pound566.27 for the ICBG and BMP-7 groups, respectively. The average cost of treatment with BMP-7 was 6.78% higher (P = 0.1) than with ICBG, and most of this (41.1%) was related to the actual price of the BMP-7. In addition to the satisfactory efficacy and safety of BMP-7 in comparison to the gold standard of ICBG, as documented in multiple studies, its cost effectiveness is advocated favourably in this analysis.

Antibacterial properties and regenerative potential of Sr2+ and Ce3+ doped fluorapatites; a potential solution for peri-implantitis.

Scaffolds and implants in orthopaedics and regenerative dentistry usually fail because of bacterial infections. A promising solution would be the development of biomaterials with both significant regenerative potential and enhanced antibacterial activity. Working towards this direction, fluorapatite was synthesised and doped with Sr2+ and Ce3+ ions in order to tailor its properties. After experiments with four common bacteria (i.e. E. Coli, S. Aureus, B. Subtilis, B. Cereus), it was found that the undoped and the Ce3+ doped fluorapatites present better antibacterial response than the Sr2+ doped material. The synthesised minerals were incorporated into chitosan scaffolds and tested with Dental Pulp Stem Cells (DPSCs) to check their regenerative potential. As was expected, the scaffolds containing Sr2+-doped fluorapatite, presented high osteoconductivity leading to the differentiation of the DPSCs into osteoblasts. Similar results were obtained for the Ce3+-doped material, since both the concentration of osteocalcin and the RUNX2 gene expression were considerably higher than that for the un-doped mineral. Overall, it was shown that doping with Ce3+ retains the good antibacterial profile of fluorapatite and enhances its regenerative potential, which makes it a promising option for dealing with conditions where healing of hard tissues is compromised by bacterial contamination.

Timing of major fracture care in polytrauma patients - An update on principles, parameters and strategies for 2020.

OBJECTIVES: Sustained changes in resuscitation and transfusion management have been observed since the turn of the millennium, along with an ongoing discussion of surgical management strategies. The aims of this study are threefold: a) to evaluate the objective changes in resuscitation and mass transfusion protocols undertaken in major level I trauma centers; b) to summarize the improvements in diagnostic options for early risk profiling in multiply injured patients and c) to assess the improvements in surgical treatment for acute major fractures in the multiply injured patient. METHODS: I. A systematic review of the literature (comprehensive search of the MEDLINE, Embase, PubMed, and Cochrane Central Register of Controlled Trials databases) and a concomitant data base (from a single Level I center) analysis were performed. Two authors independently extracted data using a pre-designed form. A pooled analysis was performed to determine the changes in the management of polytraumatized patients after the change of the millennium. II. A data base from a level I trauma center was utilized to test any effects of treatment changes on outcome. INCLUSION CRITERIA: adult patients, ISS > 16, admission < less than 24 h post trauma. Exclusion: Oncological diseases, genetic disorders that affect the musculoskeletal system. Parameters evaluated were mortality, ICU stay, ICU complications (Sepsis, Pneumonia, Multiple organ failure). RESULTS: I. From the electronic databases, 5141 articles were deemed to be relevant. 169 articles met the inclusion criteria and a manual review of reference lists of key articles identified an additional 22 articles. II. Out of 3668 patients, 2694 (73.4%) were male, the mean ISS was 28.2 (SD 15.1), mean NISS was 37.2 points (SD 17.4 points) and the average length of stay was 17.0 days (SD 18.7 days) with a mean length of ICU stay of 8.2 days (SD 10.5 days), and a mean ventilation time of 5.1 days (SD 8.1 days). Both surgical management and nonsurgical strategies have changed over time. Damage control resuscitation, dynamic analyses of coagulopathy and lactate clearance proved to sharpen the view of the worsening trauma patient and facilitated the prevention of further complications. The subsequent surgical care has become safer and more balanced, avoiding overzealous initial surgeries, while performing early fixation, when patients are physiologically stable or rapidly improving. Severe chest trauma and soft tissue injuries require further evaluation. CONCLUSIONS: Multiple changes in management (resuscitation, transfusion protocols and balanced surgical care) have taken place. Moreover, improvement in mortality rates and complications associated with several factors were also observed. These findings support the view that the management of polytrauma patients has been substantially improved over the past 3 decades.

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.