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Sepsis is a life-threatening syndrome of organ dysfunction caused by a dysregulated host response to infection characterized by excessive neutrophil infiltration into vital organs. In sepsis, patients often die of organ failure and therapies directed against endothelial cell dysfunction and tissue damage are important targets for treatment of this disease. Novel approaches are required to understand the underlying pathophysiology of neutrophil dysregulation and neutrophil-endothelial cell interactions that play a critical role in the early course of organ damage and disruption of endothelial protective barrier. Here, we review methodologies that our laboratories have employed to study neutrophil-endothelial interaction and endothelial barrier function in in vivo and in vitro models of sepsis. We will focus on in vivo rodent models of sepsis and in vitro tools that use human cell culture models under static conditions and the more physiologically relevant biomimetic microfluidic assays. This Methods paper is based on our presentation in the Master Class Symposium at the 41st Annual Conference on Shock 2018.In recent years there has been a tremendous increase in hemorrhage control by endovascular methods. Traumatic and non-traumatic hemorrhage is being more frequently managed with endografts, embolization agents and minimal invasive methods. These methods initially were used in hemodynamically stable patients only, whereas now are being implemented in acute settings and hemodynamically unstable patients. The strategy of using endovascular and combined open-endo methods approach for hemodynamic instability in trauma and non-trauma patients has been named EVTM- EndoVascular resuscitation and Trauma Management. The EVTM concept will be presented in this article, describing how it is developed and used, as well as its limitations and future aspects.Following global ischemia reperfusion injury triggered by cardiac arrest (CA) and resuscitation, the ensuing cardiac and cerebral damage would result in high mortality and morbidity. Recently, resolvin D1 has been proven to have a protective effect on regional cardiac and cerebral ischemia reperfusion injury. In this study, we investigated the effects of resolvin D1 on cardiac and cerebral outcomes after cardiopulmonary resuscitation (CPR) in a porcine model.Twenty-eight male domestic pigs weighing between 33-41 kg were randomly divided to one of the four groups sham, CPR, low-dose resolvin D1 (LRD), and high-dose resolvin D1 (HRD). Sham animals underwent the surgical preparation only. Other animals were subjected to 8 min of untreated ventricular fibrillation and then 5 min of CPR. At 5 min after resuscitation, resolvin D1 was intravenously administered with the doses of 0.3 and 0.6 μg/kg in the LRD and HRD groups, respectively. The resuscitated animals were monitored for 6 h and observed for an additional 1in D1 significantly improved post-resuscitation cardiac and cerebral outcomes in a porcine model of CA, in which the protective effects may be in a dose-dependent manner.BACKGROUND Impact of prior cardiovascular antihypertensive medication during the initial phase of septic shock in terms of catecholamine requirements and mortality has been poorly investigated and remains unclear. OBJECTIVES To investigate the association between chronic prescription of cardiovascular antihypertensive medication prior to intensive care unit (ICU) admission, catecholamine requirement and mortality in patients with septic shock. METHODS We included all consecutive patients diagnosed with septic shock within the first 24 h of ICU admission, defined as a microbiologically proven or clinically suspected infection, associated with acute circulatory failure requiring vasopressors despite adequate fluid filling. Prior cardiovascular antihypertensive medication was defined as the chronic use of betablockers (BB), calcium channel blockers (CCB), angiotensin converting enzyme inhibitor (ACEi)/ angiotensin receptor blockers (ARB). ICU-mortality was investigated using multivariate competitive risk analysis. RESULTS Among 735 patients admitted for septic shock between 2008 and 2016, 46.9% received prior cardiovascular antihypertensive medication. Prior cardiovascular antihypertensive therapy was not associated with increased norepinephrine requirements during the first 24 h (median = 0.28 μg/kg/min in patients previously treated vs. 0.26 μg/kg/min). Prior cardiovascular antihypertensive medication was not associated with a higher risk of ICU-mortality after adjustment (cause-specific hazard = 1.28, 95% confidence interval [0.98-1.66], p = 0.06). https://www.selleckchem.com/products/atogepant.html Subgroups analyses for BB, CCB and ACEi/ARB using propensity score analyses retrieved similar results. CONCLUSION In patients admitted with septic shock, prior cardiovascular antihypertensive medication seems to have limited impact on initial hemodynamic failure and catecholamine requirement.Mortality secondary to trauma related hemorrhagic shock has not improved for several decades. Underlying the stall in progress is the conundrum of effective pre-hospital interventions for hemorrhage control. As we know, neither pressing hard on the gas nor "Stay and play" have changed mortality over the last 20 years. For this reason, when dealing with effective changes that will improve severe hemorrhage mortality outcomes, there is a need for the creation of a hybrid pre-hospital model.Improvements in mortality outcomes for patients with severe hemorrhage based on evidence for common civilian prehospital procedures such as in-field intubation and immediate fluid resuscitation with crystalloid solution is weak at best. The use of tourniquets, once considered too risky to use, however, has risen dramatically in large part due success seen during their use in the military. Their use in the civilian setting shows promising results. Recently updated military Advanced Resuscitative Care (ARC) guidelines propose the use of prehospital whole blood transfusion as well as in-field use of Zone 1 Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA). Several case studies from Europe suggest these strategies are feasible for use in the civilian population, but could they be implemented in the U.S.?
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