Etomidate increases susceptibility to pneumonia in trauma patients

Purpose

To investigate the impact of etomidate on the rate of hospital-acquired pneumonia (HAP) in trauma patients and the effects of hydrocortisone in etomidate-treated patients.

Methods

This was a sub-study of the HYPOLYTE multi-centre, randomized, double-blind, placebo-controlled trial of hydrocortisone in trauma patients (NCT00563303). Inclusion criterion was trauma patient with mechanical ventilation (MV) of?≥48?h. The use of etomidate was prospectively collected. Endpoints were the results of the cosyntropin test and rate of HAP on day 28 of follow-up.

Results

Of the 149 patients enrolled in the study, 95 (64?%) received etomidate within 36?h prior to inclusion. 79 (83?%) of 95 patients receiving etomidate and 34 of the 54 (63?%) not receiving etomidate had corticosteroid insufficiency (p?=?0.006). The administration of etomidate did not alter basal cortisolemia (p?=?0.73), but it did decrease the delta of cortisolemia at 60?min (p?=?0.007). There was a correlation between time from etomidate injection to inclusion in the study and sensitivity to corticotropin (R ²?=?0.19; p?=?0.001). Forty-nine (51.6?%) patients with etomidate and 16 (29.6?%) patients without etomidate developed HAP by day 28 (p?=?0.009). Etomidate was associated with HAP on day 28 in the multivariate analysis (hazard ratio 2.48; 95?% confidence interval 1.19–5.18; p?=?0.016). Duration of MV with or without etomidate was not significantly different (p?=?0.278). Among etomidate-exposed patients, 18 (40?%) treated with hydrocortisone developed HAP compared with 31 (62?%) treated with placebo (p?=?0.032). Etomidate-exposed patients treated with hydrocortisone had fewer ventilator days (p?Conclusions Among the patients enrolled in the study, etomidate did not alter basal cortisolemia, but it did decrease reactivity to corticotropin. We suggest that in trauma patients, etomidate is an independent risk factor for HAP and that the administration of hydrocortisone should be considered after etomidate use.     

The miR-17-92 cluster and its target THBS1 are differentially expressed in angiosarcomas dependent on MYC amplification

Angiosarcomas (ASs) represent a heterogeneous group of malignant vascular tumors that may occur spontaneously as primary tumors or secondarily after radiation therapy or in the context of chronic lymphedema. Most secondary ASs have been associated with MYC oncogene amplification, whereas the role of MYC abnormalities in primary AS is not well defined. Twenty-two primary and secondary ASs were analyzed by array-comparative genomic hybridization (aCGH) and by deep sequencing of small RNA libraries. By aCGH and subsequently confirmed by fluorescence in situ hybridization, MYC amplification was identified in three out of six primary tumors and in 8 out of 12 secondary AS. We have also found MAML1 as a new potential oncogene in MYC-amplified AS. Significant upregulation of the miR-17-92 cluster was observed in MYC-amplified AS compared to AS lacking MYC amplification and the control group (other vascular tumors, nonvascular sarcomas). Moreover, MYC-amplified ASs were associated with a significantly lower expression of thrombospondin-1 (THBS1) than AS without MYC amplification or controls. Altogether, our study implicates MYC amplification not only in the pathogenesis of secondary AS but also in a subset of primary AS. Thus, MYC amplification may play a crucial role in the angiogenic phenotype of AS through upregulation of the miR-17-92 cluster, which subsequently downregulates THBS1, a potent endogenous inhibitor of angiogenesis.     

Gap junctional coupling with cardiomyocytes is necessary but not sufficient for cardiomyogenic differentiation of cocultured human mesenchymal stem cells

Gap junctional coupling is important for functional integration of transplanted cells with host myocardium. However, the role of gap junctions in cardiomyogenic differentiation of transplanted cells has not been directly investigated. The objective of this work is to study the role of connexin43 (Cx43) in cardiomyogenic differentiation of human mesenchymal stem cells (hMSCs). Knockdown of Cx43 gene expression (Cx43↓) was established in naturally Cx43-rich fetal amniotic membrane (AM) hMSCs, while Cx43 was overexpressed (Cx43↑) in inherently Cx43-poor adult adipose tissue (AT) hMSCs. The hMSCs were exposed to cardiomyogenic stimuli by coincubation with neonatal rat ventricular cardiomyocytes (nrCMCs) for 10 days. Differentiation was assessed by immunostaining and whole-cell current clamping. To establish whether the effects of Cx43 knockdown could be rescued, Cx45 was overexpressed in Cx43↓ fetal AM hMSCs. Ten days after coincubation, not a single Cx43↓ fetal AM hMSC, control adult AT MSC, or Cx43↑ adult AT mesenchymal stem cell (MSC) expressed α-actinin, while control fetal AM hMSCs did (2.2% ± 0.4%, n = 5,000). Moreover, functional cardiomyogenic differentiation, based on action potential recordings, occurred only in control fetal AM hMSCs. Of interest, Cx45 overexpression in Cx43↓ fetal AM hMSCs restored their ability to undergo cardiomyogenesis (1.6% ± 0.4%, n = 2,500) in coculture with nrCMCs. Gap junctional coupling is required for differentiation of fetal AM hMSCs into functional CMCs after coincubation with nrCMCs. Heterocellular gap junctional coupling thus plays an important role in the transfer of cardiomyogenic signals from nrCMCs to fetal hMSCs but is not sufficient to induce cardiomyogenic differentiation in adult AT hMSCs.     

Interindividual differences in circadian rhythmicity and sleep homeostasis in older people: effect of a PER3 polymorphism

Aging is associated with marked changes in the timing, consolidation and structure of sleep. Older people wake up frequently, get up earlier and have less slow wave sleep than young people, although the extent of these age-related changes differs considerably between individuals. Interindividual differences in homeostatic sleep regulation in young volunteers are associated with the variable-number, tandem-repeat (VNTR) polymorphism (rs57875989) in the coding region of the circadian clock gene PERIOD3 (PER3). However, predictors of these interindividual differences have yet to be identified in older people. Sleep electroencephalographic (EEG) characteristics and circadian rhythms were assessed in 26 healthy older volunteers (55-75 years) selected on the basis of homozygosity for either the long or short allele of the PER3 polymorphism. Homozygosity for the longer allele (PER3(5/5)) associated with a phase-advance in the circadian melatonin profile and an earlier occurrence of the melatonin peak within the sleep episode. Furthermore, older PER3(5/5) participants accumulated more nocturnal wakefulness, had increased EEG frontal delta activity (0.75-1.50 Hz), and decreased EEG frontal sigma activity (11-13 Hz) during non-rapid eye movement (REM) sleep compared with PER3(4/4) participants. Our results indicate that the polymorphism in the clock gene PER3 may contribute to interindividual differences in sleep and circadian physiology in older people.     

The arterial supply of the coracoid process

Objective

The aim of this study was to describe the arterial supply of the coracoid process and to define its possible involvement in complications of Latarjet procedure.

Method

Five shoulder dissections were performed to highlight the extraosseous blood supply of the coracoid process. Postmortem arteriographies of the upper limb were performed. Diaphanization of a scapula enabled to view its intraosseous blood supply.

Results

The vertical part of coracoid process was supplied by supra-scapular artery, and the horizontal part by branches of the axillary artery.

Discussion and conclusion

This anatomical study has shown that the coracoid process had its own blood supply. During the Latarjet procedure, vascular sacrifices are mandatory to allow coracoid process transfer to the scapular neck. Such sacrifices could explain lysis or non-union of the coracoid process after Latarjet procedure. Preservation of axillary artery branches supplying horizontal part of the coracoid process could be a possible solution to prevent non-union and lysis of the bone transfer.