Evidence-based guidelines for bleeding in trauma patients: where do we go from here?

The development of evidence-based guidelines has gained popularity as a strategy to reduce variation in practice and to orient clinical care around documentable best practices. Based on available data, the new European guidelines for the management of bleeding in the trauma patient do deliver a number of sound recommendations. However, some issues remain controversial and, like many guidelines, the actual translation of these evidence-based recommendations into routine clinical practice protocols continues to leave opportunity for variation. Nevertheless, this consensus guideline provides an excellent starting point. As evidence continues to accumulate, future iterations should provide greater specificity and move us closer to the definitive best practice

Macroeconomic trends and practice models impacting acute care surgery

Acute care surgery (ACS) diagnoses are responsible for approximately a quarter of the costs of inpatient care in the US government, and individuals will be responsible for a larger share of the costs of this healthcare as the population ages. ACS as a specialty thus has the opportunity to meet a significant healthcare need, and by optimizing care delivery models do so in a way that improves both quality and value. ACS practice models that have maintained or added emergency general surgery (EGS) and even elective surgery have realized more operative case volume and surgeon satisfaction. However, vulnerabilities exist in the ACS model. Payer mix in a practice varies by geography and distribution of EGS, trauma, critical care, and elective surgery. Critical care codes constitute approximately 25% of all billing by acute care surgeons, so even small changes in reimbursement in critical care can have significant impact on professional revenue. Staffing an ACS practice can be challenging depending on reimbursement and due to uneven geographic distribution of available surgeons. Empowered by an understanding of economics, using team-oriented leadership inherent to trauma surgeons, and in partnership with healthcare organizations and regulatory bodies, ACS surgeons are positioned to significantly influence the future of healthcare in the USA

Estrogen treatment following severe burn injury reduces brain inflammation and apoptotic signaling

<p>Abstract</p> <p>Background</p> <p>Patients with severe burn injury experience a rapid elevation in multiple circulating pro-inflammatory cytokines, with the levels correlating with both injury severity and outcome. Accumulations of these cytokines in animal models have been observed in remote organs, however data are lacking regarding early brain cytokine levels following burn injury, and the effects of estradiol on these levels. Using an experimental animal model, we studied the acute effects of a full-thickness third degree burn on brain levels of TNF-α, IL-1β, and IL-6 and the protective effects of acute estrogen treatment on these levels. Additionally, the acute administration of estrogen on regulation of inflammatory and apoptotic events in the brain following severe burn injury were studied through measuring the levels of phospho-ERK, phospho-Akt, active caspase-3, and PARP cleavage in the placebo and estrogen treated groups.</p> <p>Methods</p> <p>In this study, 149 adult Sprague-Dawley male rats received 3rd degree 40% total body surface area (TBSA) burns. Fifteen minutes following burn injury, the animals received a subcutaneous injection of either placebo (n = 72) or 17 beta-estradiol (n = 72). Brains were harvested at 0.5, 1, 2, 4, 6, 8, 12, 18, and 24 hours after injury from the control (n = 5), placebo (n = 8/time point), and estrogen treated animals (n = 8/time point). The brain cytokine levels were measured using the ELISA method. In addition, we assessed the levels of phosphorylated-ERK, phosphorylated-Akt, active caspase-3, and the levels of cleaved PARP at the 24 hour time-point using Western blot analysis.</p> <p>Results</p> <p>In burned rats, 17 beta-estradiol significantly decreased the levels of brain tissue TNF-α (~25%), IL-1β (~60%), and IL-6 (~90%) when compared to the placebo group. In addition, we determined that in the estrogen-treated rats there was an increase in the levels of phospho-ERK (<it>p </it>< 0.01) and Akt (<it>p </it>< 0.05) at the 24 hour time-point, and that 17 beta-estradiol blocked the activation of caspase-3 (<it>p </it>< 0.01) and subsequent cleavage of PARP (<it>p </it>< 0.05).</p> <p>Conclusion</p> <p>Following severe burn injury, estrogens decrease both brain inflammation and the activation of apoptosis, represented by an increase in the levels of phospho-Akt and inhibition of caspase-3 activation and PARP cleavage. Results from these studies will help further our understanding of how estrogens protect the brain following burn injury, and may provide a novel, safe, and effective clinical treatment to combat remote secondary burn injury in the brain and to preserve cognition.</p

A genomic storm in critically injured humans

Critical injury in humans induces a genomic storm with simultaneous changes in expression of innate and adaptive immunity genes

Mitochondrial ROS Induces Cardiac Inflammation via a Pathway through mtDNA Damage in a Pneumonia-Related Sepsis Model.

We have previously shown that mitochondria-targeted vitamin E (Mito-Vit-E), a mtROS specific antioxidant, improves cardiac performance and attenuates inflammation in a pneumonia-related sepsis model. In this study, we applied the same approaches to decipher the signaling pathway(s) of mtROS-dependent cardiac inflammation after sepsis. Sepsis was induced in Sprague Dawley rats by intratracheal injection of S. pneumoniae. Mito-Vit-E, vitamin E or vehicle was administered 30 minutes later. In myocardium 24 hours post-inoculation, Mito-Vit-E, but not vitamin E, significantly protected mtDNA integrity and decreased mtDNA damage. Mito-Vit-E alleviated sepsis-induced reduction in mitochondria-localized DNA repair enzymes including DNA polymerase γ, AP endonuclease, 8-oxoguanine glycosylase, and uracil-DNA glycosylase. Mito-Vit-E dramatically improved metabolism and membrane integrity in mitochondria, suppressed leakage of mtDNA into the cytoplasm, inhibited up-regulation of Toll-like receptor 9 (TLR9) pathway factors MYD88 and RAGE, and limited RAGE interaction with its ligand TFAM in septic hearts. Mito-Vit-E also deactivated NF-κB and caspase 1, reduced expression of the essential inflammasome component ASC, and decreased inflammatory cytokine IL-1β. In vitro, both Mito-Vit-E and TLR9 inhibitor OND-I suppressed LPS-induced up-regulation in MYD88, RAGE, ASC, active caspase 1, and IL-1β in cardiomyocytes. Since free mtDNA escaped from damaged mitochondria function as a type of DAMPs to stimulate inflammation through TLR9, these data together suggest that sepsis-induced cardiac inflammation is mediated, at least partially, through mtDNA-TLR9-RAGE. At last, Mito-Vit-E reduced the circulation of myocardial injury marker troponin-I, diminished apoptosis and amended morphology in septic hearts, suggesting that mitochondria-targeted antioxidants are a potential cardioprotective approach for sepsis