Changes in the temporal distribution of in-hospital mortality in severely injured patients-An analysis of the TraumaRegister DGU.

BACKGROUND: The temporal distribution of trauma mortality has been classically described as a trimodal pattern with an immediate, early and late peak. In modern health care systems this time distribution has changed. METHODS: Data from the TraumaRegister DGU was analysed retrospectively. Between 2002 and 2015, all registered in-hospital deaths with an Injury Severity Score (ISS) ≥ 16 were evaluated considering time of death, trauma mechanism, injured body area, age distribution, rates of sepsis and multiple organ failure. Pre-hospital and post-discharge trauma deaths were not considered. RESULTS: 78 310 severely injured patients were registered, non-survivors constituted 14 816, representing an in-hospital mortality rate of 18.9%. Mean ISS of non-survivors was 36.0±16.0, 66.7% were male, mean age was 59.5±23.5. Within the first hour after admission to hospital, 10.8% of deaths occurred, after 6 hours the percentage increased to 25.5%, after 12 hours 40.0%, after 24 hours 53.2% and within the first 48 hours 61.9%. Mortality showed a constant temporal decrease. Severe head injury (defined by Abbreviated Injury Scale, AIS-Head≥3) was found in 76.4% of non-survivors. Patients with an isolated head injury showed a more distinct decrease in survival rate, which was accentuated in the first days after admission. The correlation of age and time of death showed a proportional increase with age (55-74a). The rate of sepsis and multiple organ failure among non-survivors was 11.5% and 70.1%, respectively. CONCLUSION: In a modern trauma care system, the mortality distribution of severely injured patients has changed its pattern, where especially the third peak is no longer detectable.

Bone marrow T cells from the femur are similar to iliac crest derived cells in old age and represent a useful tool for studying the aged immune system.

BACKGROUND: CD4+ and CD8+ T cells reside in the human bone marrow (BM) and show a heightened activation state. However, only small sample sizes are available from sources such as the iliac crest. Larger samples can be obtained from the femur in the course of hip replacement surgery. It was therefore the goal of the present study to compare the phenotype and function of BM T cells from different sources from elderly persons and to investigate how femur derived bone marrow T cells can serve as a tool to gain a better understanding of the role of adaptive immune cells in the BM in old age. RESULTS: Bone marrow mononuclear cells (BMMC) were isolated from either the iliac crest or the femur shaft. As expected the yield of mononuclear cells was higher from femur than from iliac crest samples. There were no phenotypic differences between BMMC from the two sources. Compared to PBMC, both BM sample types contained fewer naïve and more antigen experienced CD4+ as well as CD8+ T cells, which, in contrast to peripheral cells, expressed CD69. Cytokine production was also similar in T cells from both BM types. Larger sample sizes allowed the generation of T cell lines from femur derived bone marrow using non-specific as well as specific stimulation. The phenotype of T cell lines generated by stimulation with OKT-3 and IL-2 for two weeks was very similar to the one of ex vivo BM derived T cells. Such lines can be used for studies on the interaction of different types of BM cells as shown by co-culture experiments with BM derived stromal cells. Using CMVNLV specific T cell lines we additionally demonstrated that BM samples from the femur are suitable for the generation of antigen specific T cell lines, which can be used in studies on the clonal composition of antigen specific BM T cells. CONCLUSION: In conclusion, our results demonstrate that BMMC from the femur shaft are a useful tool for studies on the role of T cells in the BM in old age.

Pooled outcome of total hip arthroplasty with the CementLess Spotorno (CLS) system: a comparative analysis of clinical studies and worldwide arthroplasty register data.

PURPOSE: Our aim was to elucidate the pooled outcome of the CementLess Spotorno (CLS) system in total hip arthroplasty (THA). METHODS: We compared the outcome of clinical inventor studies, independent clinical studies, and worldwide register data. The main endpoints for analysis were revision rates. RESULTS: Twenty clinical studies were evaluated and, with one exception, overall found revision rates largely in line with register data. Revision rates (revisions per 100 observed component years) range from 0.15 (inventor study) to 0.28 (independent studies) and 0.43 (register datasets). CONCLUSION: Data of journal publications and register datasets using the CLS system do not differ significantly with respect to revision rates. Only the initial inventor study reports a revision rate three times lower than in pooled worldwide register datasets.

Revision rate of Birmingham Hip Resurfacing arthroplasty: comparison of published literature and arthroplasty register data.

PURPOSE: Hip resurfacing arthroplasty has gained popularity for treating young and active patients who have arthritis. There are two major data sources for assessing outcome and revision rate after total joint arthroplasty: sample-based clinical trials and national arthroplasty registers. The purpose of this study was to evaluate the outcome of the Birmingham Hip Resurfacing (BHR) arthroplasty in terms of revision rate as reported in clinical studies and recorded by national arthroplasty registers. METHODS: A comprehensive literature research was performed from English-language, peer-reviewed journals and annual reports from national joint arthroplasty registers worldwide. Only publications from MEDLINE-listed journals were included. The revision rate was used as the primary outcome parameter. In order to allow for direct comparison of different data sets, calculation was based on revisions per 100 observed component years. For statistical analysis, confidence intervals (CI) were calculated. RESULTS: A total of 18,708 implants, equivalent to 106,565 observed component years, were analysed in the follow-up studies. The register reports contained 9,806 primary cases corresponding to 44,294 observed component years. Statistical analysis revealed a significant difference in revisions per 100 observed component years between the development team (0.27; CI: 0.14-0.40) and register data (0.74; CI: 0.72-0.76). CONCLUSION: The BHR arthroplasty device shows good results in terms of revision rate in register data as well as in clinical studies. However, the excellent results reported by the development team are not reproducible by other surgeons. Based on the results of our study, we believe that comprehensive national arthroplasty registers are the most suitable tool for assessing hip arthroplasty revision rate.

Enhanced cell therapy for ischemic heart disease.

Stem cell therapy is regarded as an innovative strategy to intervene in degenerative heart disease. The efficacy of stem cell therapy to regenerate ischemic myocardium has been limited by inadequate numbers of injected cells, unacceptable cell engraftment or long-term survival, and from restrictions associated with the method of delivery. In this review, we provide an overview of the literature emphasizing several strategies which enable improved results after cell therapy for ischemic heart disease. Enhanced cell therapy includes (a) combination of cell grafts either pre-co-cultured or co-injected cells, (b) transplantation of genetically modified cells, or (c) simultaneous administration of control released growth factors, (d) cell preconditioning, (e) use of adjunctive systemic therapy, or (f) repetitive cell therapy. Future studies should focus on the development of strategies for optimization of cell delivery, which will enable easy isolation of adequate cell volume and optimal functional results.

Neoangiogenesis after combined transplantation of skeletal myoblasts and angiopoietic progenitors leads to increased cell engraftment and lower apoptosis rates in ischemic heart failure.

OBJECTIVES: We previously reported that combined transplantation of skeletal myoblasts and AC-133+ cells leads to improved left ventricular function, reduced infarct size and myocardial apoptosis in a model of chronic ischemia. The aim of this study is to elucidate on the possible mechanisms and to assess new implications in increasing cell therapy efficacy in chronic ischemia. METHODS: Heart failure was induced by LAD-ligation in nude rats. (a) Homologous skeletal myoblasts (SM), (b) human derived AC-133+ cells (SC), (c) combination of both cells (Comb) and (d) culture medium (CM) were injected in the infarct and peri-infarct area, respectively, four weeks after infarction. Cell engraftment was detected by fluorescence microscopy and confirmed by immunohistochemical techniques. Cardiac gene expression levels of VEFG-A, cardiac troponin, ACTA2, SDF-1, TGF-beta-1, were assessed by RT-PCR. RESULTS: Both cell types were detected in the injection areas four weeks after cell transplantation. Double cell therapy led to increased cell engraftment (SM: 52+/-13/mm(2), SC: 45+/-8 in the combination group vs. SM: 31+/-9 and 23+/-7 in the monotherapy groups, P=0.007). This effect was confirmed using PCR. Apoptotic index among engrafted cells was significantly lower in the Comb group (Comb: 0.53+/-0.12 for myoblasts and 0.34+/-0.09 for SC, vs. SM: 0.76+/-0.19 and SC: 0.63+/-0.16, P=0.013). Expression of cardiac troponin was higher in the combination group in the peri-infarct area. Evaluation of capillary density revealed increased angiogenesis in the combination group (Comb: 12.3+/-2.3, SM: 5.2+/-1.2, SC: 8.3+/-1.8, P=0.002). Neoangiogenesis was associated with higher levels of VEGF-A and TGF-beta in the injection areas as detected by RT-PCR. The higher SDF-1 expression in the injected areas implies an increased secretion of chemoattractants by the injected cells, which suggests that the effect of combined cell transplantation is mainly associated with paracrine mechanisms. CONCLUSIONS: The mechanism of functional improvement after combined transplantation of skeletal myoblasts and AC-133+ progenitors in ischemic heart failure is mainly associated with increased angiogenesis based on paracrine factors, which leads to improved survival and lower apoptosis rates of the injected cells.

Combined transplantation of skeletal myoblasts and angiopoietic progenitor cells reduces infarct size and apoptosis and improves cardiac function in chronic ischemic heart failure.

OBJECTIVES: Cellular cardiomyoplasty using skeletal myoblasts or angiopoietic progenitor cells offers a promising approach for the treatment of ischemic heart failure. Although several studies have shown encouraging results in acute myocardial infarction, the efficacy of cell therapy using skeletal myoblasts and angiopoietic progenitor cells in chronic ischemic heart disease remains undetermined. METHODS: Ischemic heart failure was induced by left anterior descending coronary artery ligation in nude rats: (1) Culture medium, (2) homologous skeletal myoblasts (SM), (3) human AC-133+ cells (SC), and (4) both skeletal myoblasts and AC-133+ cells (Comb) were injected in the infarct (SM) and peri-infarct area (SC) 4 weeks after infarction. Assessment of myocardial function included echocardiography 4 weeks after cell delivery. Histology was based on quantification of myocardial fibrosis, apoptosis, and capillary density. RESULTS: Left ventricular dilatation was attenuated and ejection fraction improved significantly after cell transplantation (SM: 59.4% +/- 8.8%, SC: 60.3% +/- 6.6%, Comb: 68.2% +/- 5.6% vs control: 41.5% +/- 7.4%, P = .0013). Quantification of scar tissue showed a significant reduction of infarct area in cell-treated animals (SM: 22.3% +/- 9.1%, SC: 19.8% +/- 7.6%, Comb: 13.2% +/- 5.8% vs controls: 36.5% +/- 8.2%, P = .008). Improvement of myocardial function was associated with reduced apoptotic index (SM: 3.2% +/- 0.9%, SC: 3.1% +/- 0.6%, Comb: 1.8% +/- 0.8% vs controls: 10.3% +/- 1.6%, P = .0002) and increased vascular density (SM: 5.2 +/- 1.2, SC: 8.3 +/- 1.8, Comb: 12.3 +/- 2.3, controls: 1.9 +/- 0.3, all capillary vessels/high-power field, P = .007) in animals after cellular cardiomyoplasty. CONCLUSIONS: Combined transplantation of skeletal myoblasts and angiopoietic progenitor cells results in ventricular function improvement, reduction of scar size and myocardial apoptosis, and increased neoangiogenesis in chronic ischemia. Clinical studies are warranted to prove this new therapeutic concept.