Blunt Cardiac Injury in the Severely Injured - A Retrospective Multicentre Study.

BACKGROUND: Blunt cardiac injury is a rare trauma entity. Here, we sought to evaluate the relevance and prognostic significance of blunt cardiac injury in severely injured patients. METHODS: In a retrospective multicentre study, using data collected from 47,580 patients enrolled to TraumaRegister DGU (1993-2009), characteristics of trauma, prehospital / hospital trauma management, and outcome analysis were correlated to the severity of blunt cardiac injury. The severity of cardiac injury was assessed according to the abbreviated injury score (AIS score 1-6), the revised injury severity score (RISC) allowed comparison of expected outcome with injury severity-dependent outcome. N = 1.090 had blunt cardiac trauma (AIS 1-6) (2.3% of patients). RESULTS: Predictors of blunt cardiac injury could be identified. Sternal fractures indicate a high risk of the presence of blunt cardiac injury (AIS 0 [control]: 3.0%; AIS 1: 19.3%; AIS 2-6: 19.1%). The overall mortality rate was 13.9%, minor cardiac injury (AIS 1) and severe cardiac injury (AIS 2-6) are associated with higher rates. Severe blunt cardiac injury (AIS 4 and AIS 5-6) is associated with a higher mortality (OR 2.79 and 4.89, respectively) as compared to the predicted average mortality (OR 2.49) of the study collective. CONCLUSION: Multiple injured patients with blunt cardiac trauma are at high risk to be underestimated. Careful evaluation of trauma patients is able to predict the presence of blunt cardiac injury. The severity of blunt cardiac injury needs to be stratified according to the AIS score, as the patients' outcome is dependent on the severity of cardiac injury.

Whole-body CT in haemodynamically unstable severely injured patients--a retrospective, multicentre study.

BACKGROUND: The current common and dogmatic opinion is that whole-body computed tomography (WBCT) should not be performed in major trauma patients in shock. We aimed to assess whether WBCT during trauma-room treatment has any effect on the mortality of severely injured patients in shock. METHODS: In a retrospective multicenter cohort study involving 16719 adult blunt major trauma patients we compared the survival of patients who were in moderate, severe or no shock (systolic blood pressure 90-110,<90 or >110 mmHg) at hospital admission and who received WBCT during resuscitation to those who did not. Using data derived from the 2002-2009 version of TraumaRegister®, we determined the observed and predicted mortality and calculated the standardized mortality ratio (SMR) as well as logistic regressions. FINDINGS: 9233 (55.2%) of the 16719 patients received WBCT. The mean injury severity score was 28.8±12.1. The overall mortality rate was 17.4% (SMR  = 0.85, 95%CI 0.81-0.89) for patients with WBCT and 21.4% (SMR = 0.98, 95%CI 0.94-1.02) for those without WBCT (p<0.001). 4280 (25.6%) patients were in moderate shock and 1821 (10.9%) in severe shock. The mortality rate for patients in moderate shock with WBCT was 18.1% (SMR 0.85, CI95% 0.78-0.93) compared to 22.6% (SMR 1.03, CI95% 0.94-1.12) to those without WBCT (p<0.001, p = 0.002 for the SMRs). The mortality rate for patients in severe shock with WBCT was 42.1% (SMR 0.99, CI95% 0.92-1.06) compared to 54.9% (SMR 1.10, CI95% 1.02-1.16) to those without WBCT (p<0.001, p = 0.049 for the SMRs). Adjusted logistic regression analyses showed that WBCT is an independent predictor for survival that significantly increases the chance of survival in patients in moderate shock (OR = 0.73; 95%CI 0.60-0.90, p = 0.002) as well as in severe shock (OR = 0.67; 95%CI 0.52-0.88, p = 0.004). The number needed to scan related to survival was 35 for all patients, 26 for those in moderate shock and 20 for those in severe shock. CONCLUSIONS: WBCT during trauma resuscitation significantly increased the survival in haemodynamically stable as well as in haemodynamically unstable major trauma patients. Thus, the application of WBCT in haemodynamically unstable severely injured patients seems to be safe, feasible and justified if performed quickly within a well-structured environment and by a well-organized trauma team.

Reprogramming of active and repressive histone modifications following nuclear transfer with rabbit mesenchymal stem cells and adult fibroblasts.

Following nuclear transfer (NT) the epigenetic state of a donor nucleus must be reprogrammed to an embryonic one. To evaluate the efficiency of nuclear reprogramming, we monitored the levels of histone H3 di/tri-methylated on lysine 4 (H3K4m2/3), a marker for transcriptionally active/permissive euchromatin, and of histone H3 tri-methylated on lysine 27 (H3K27m3), a modification associated with facultative heterochromatin, in embryos cloned using rabbit mesenchymal stem cells (MSC) and adult fibroblasts (RAF) isolated from the same animals. In vivo fertilized, in vitro cultured embryos served as controls. H3K27m3 was undetectable in all stages of control embryos except for weak staining in a few blastocyst cells. A similar situation was found in all NT embryos irrespective of the type of donor cells used, although both MSC and RAF stained substantially for H3K27m3. H3K4m2/3 levels were very high in one- and two-cell control embryos, but then decreased to reach a minimum at the eight-cell stage, and finally increased again to initial levels at the morula and blastocyst stage. Reprogramming of H3K4m2/3 differed remarkably among the different types NT embryos as well as between NT embryos and control embryos, and was apparently dependent on the type of donor cells. Interestingly, abnormal reprogramming of H3K4m2/3 was observed in NT embryos derived from both MSC and RAF, donor cell types with markedly different proliferation capacity. Our study demonstrates that the repressive chromatin modification, H3K27m3, is faithfully reprogrammed in NT embryos derived from MSC or RAF, while reprogramming of the activating chromatin modification, H3K4m2/3, is quite variable and does not reflect the situation observed in control embryos derived by fertilization.

Introducing a single-cell-derived human mesenchymal stem cell line expressing hTERT after lentiviral gene transfer.

Human mesenchymal stem cells (hMSCs) can be readily isolated from bone marrow and differentiate into multiple tissues, making them a promising target for future cell and gene therapy applications. The low frequency of hMSCs in bone marrow necessitates their isolation and expansion in vitro prior to clinical use, but due to senescence-associated growth arrest during culture, limited cell numbers can be generated. The lifespan of hMSCs has been extended by ectopic expression of human telomerase reverse transcriptase (hTERT) using retroviral vectors. Since malignant transformation was observed in hMSCs and retroviral vectors cause insertional mutagenesis, we ectopically expressed hTERT using lentiviral gene transfer. Single-cell-derived hMSC clones expressing hTERT did not show malignant transformation in vitro and in vivo after extended culture periods. There were no changes observed in the expression of tumour suppressor genes and karyotype. Cultured hMSCs lack telomerase activity, but it was significantly increased by ectopic expression of hTERT. HTERT expression prevented hMSC senescence and the cells showed significantly higher and unlimited proliferation capacity. Even after an extended culture period, hMSCs expressing hTERT preserved their stem cells character as shown by osteogenic, adipogenic and chondrogenic differentiation. In summary, extending the lifespan of human mesenchymal stem cells by ectopic expression of hTERT using lentiviral gene transfer may be an attractive and safe way to generate appropriate cell numbers for cell and gene therapy applications.