Effect of early use of noradrenaline on in-hospital mortality in haemorrhagic shock after major trauma: a propensity-score analysis.

BACKGROUND: The role of vasopressors in trauma-related haemorrhagic shock (HS) remains a matter of debate. They are part of the most recent European recommendations on the management of HS and are regularly used in France. We assessed the effect of early administration of noradrenaline in 24 h mortality of trauma patients in HS, using a propensity-score analysis. METHODS: The study included patients from a multicentre prospective regional trauma registry. HS was defined as transfusion of ≥4 erythrocyte-concentrate units during the first 6 h. Patients with a Glasgow coma scale=3 and pre-hospital traumatic cardiac arrest were excluded. The main outcome measure was in-hospital mortality. The explicative and adjustment variables for the outcome and treatment allocation were predetermined by a Delphi method. The in-hospital mortality of patients with and without early administration of noradrenaline was compared in a propensity-score model, including all predetermined variables. RESULTS: Of 7141 patients in the registry in the study period, 6353 were screened and 518 patients in HS (201 with early noradrenaline use and 317 without) were included and analysed. After propensity-score matching, 100 patients remained in each group, and the hazard-ratio mortality was 0.95 (95% confidence interval: 0.45-2.01; P=0.69). CONCLUSIONS: The results of the present study suggest that noradrenaline use in the early phase of traumatic HS does not seem to affect mortality adversely. This observation supports a rationale for equipoise in favour of a prospective trial of the use of vasopressors in HS after trauma.

Extracorporeal life support (ECLS) for refractory cardiac arrest after drowning: an 11-year experience.

AIM: Neuroprotective effects of hypothermia may explain surprisingly high survival rates reported after drowning in cold water despite prolonged submersion. We described a cohort of refractory hypothermic cardiac arrests (CA) due to drowning treated by extracorporeal life support (ECLS) and aimed to identify criteria associated with 24-h survival. METHODS: Eleven-year period (2002-2012) retrospective study in the surgical intensive care unit (ICU) of a tertiary hospital (European Hospital Georges Pompidou, Paris, France). All consecutive hypothermic patients admitted for refractory CA after drowning in the Seine River were included. Patients with core temperature below 30°C and submersion duration of less than 1h were potentially eligible for ECLS resuscitation. RESULTS: Forty-three patients were admitted directly to the ICU during the study period. ECLS was initiated in 20 patients (47%). Among these 20 patients, only four (9%) survived more than 24h. A first hospital core temperature ≤26°C and a potassium serum level between 4.2 and 6mM at hospital admission have a sensitivity of 100% [95%CI: 28-100%] and a specificity of 100% [95%CI: 71-100%] to discriminate patients who survived more than 24h. Overall survival at ICU discharge and at 6-months was 5% [95%CI: 1-16%] (two patients). CONCLUSIONS: Despite patient hypothermia and aggressive resuscitation with ECLS, the observed survival rate is low in the present cohort. Like existing algorithms for ECLS management in avalanche victims, we recommend to use first core temperature and potassium serum level to indicate ECLS for refractory CA due to drowning.

[Perioperative anaesthetic practices in liver transplantation in France: Evolution between 2004 and 2008]. / Prise en charge anesthésique des transplantations hépatiques : évolution des pratiques périopératoires en France entre 2004 et 2008.

OBJECTIVES: To determine the evolution of French perioperative anaesthetic practices in liver transplantation between 2004 and 2008. STUDY DESIGN: Phone survey. METHODS: In 2004 and 2008, a similar questionnaire has been administered by phone to a senior anaesthesiologist from each French centre performing adult liver transplantation (n = 21). Results were compared using Fisher test and p < 0.05 was considered significant. RESULTS: Between 2004 and 2008, there was a trend towards an increase of centres performing transplantation for more than 40% of Child C patients (p = 0.1). Simultaneously, work force dedicated to liver transplantation cases has been reduced since in 2008, one anaesthesiologist was in charge in 90% of the centres (p = 0.06 vs 2004). Perioperative practices remained largely heterogeneous between centres with regard to hemodynamic monitoring, fluid and blood products management, antifibrinolytics use or postoperative analgesia. CONCLUSIONS: This French survey has shown a reduction of work force dedicated to a liver transplantation from 2004 to 2008 simultaneously with a trend towards a greater severity of liver recipients. Practices heterogeneity reflect at least in part, unresolved questions about the best perioperative management for liver transplantation and the need for guidelines. Working for standardization of our practices and multicentric trials could allow gaining a better understanding of what should be the good practices in perioperative management of liver transplantation.

Maintenance of cellular proliferation by adenovirus early region 1A in fibroblasts conditionally immortalized by using simian virus 40 large T antigen requires conserved region 1.

Various mutants of adenovirus E1A were assayed for their ability to complement the growth defect at the nonpermissive temperature for the cell line tsa14 which was isolated by immortalizing rat embryo fibroblasts with the thermolabile large T antigen of tsA58. This cell line grows indefinitely at the permissive temperature but undergoes rapid growth arrest upon shift up to the nonpermissive temperature. Since this growth arrest can be overcome by introduction of wild-type simian virus 40 large T antigen, human papillomavirus 16 E7, and adenovirus E1A, the tsa14 cells provided an excellent system for defining regions of E1A necessary for complementation of the growth defect. We demonstrate that conserved region 1 (CR1) is the region of E1A required for complementation. While CR2 of E1A has been shown to be required for the immortalization of primary cells and is also necessary for the binding of the 105-kDa retinoblastoma protein, mutations within this region did not abrogate complementation of the growth defect. However, since both CR1 and CR2 have previously been shown to be absolutely required for immortalization of primary cells by adenovirus E1A, this evidence suggests that the tsa14 system assays for the maintenance of proliferation and that this requires CR1.

The Pseudomonas savastanoi tryptophan-2-mono-oxygenase is biologically active in Nicotiana tabacum.

It has been proposed that the "eukaryotic" T-DNA-encoded indole-3-acetic acid (IAA) biosynthesis genes of Agrobacterium tumefaciens and their prokaryotic counterpart in Pseudomonas savastanoi originated from common ancestor genes. This paper provides additional evidence for the functional similarity between the gene products. We have demonstrated that a chimeric gene consisting of the coding sequence of the P. savastanoi tryptophan-2-mono-oxygenase (iaaM gene) and a plant promoter encodes an active enzyme in Nicotiana tabacum. Transformants obtained with this chimeric gene grew as a callus on hormone-free media. No stably transformed plantlets could be isolated. The callus tissues contained extremely high levels of indole-3-acetamide and slightly elevated levels of IAA. Either indole-3-acetamide by itself has a low auxin activity or, alternatively, it is converted aspecifically and at low rates into IAA. The P. savastanoi tryptophan-2-mono-oxygenase activity in plants is also able to detoxify the amino-acid analogue 5-methyltryptophan. This property can be used for positive selection of transformed calli.