Early release of high mobility group box nuclear protein 1 after severe trauma in humans: role of injury severity and tissue hypoperfusion

IntroductionHigh mobility group box nuclear protein 1 (HMGB1) is a DNA nuclear binding protein that has recently been shown to be an early trigger of sterile inflammation in animal models of trauma-hemorrhage via the activation of the Toll-like-receptor 4 (TLR4) and the receptor for the advanced glycation endproducts (RAGE). However, whether HMGB1 is released early after trauma hemorrhage in humans and is associated with the development of an inflammatory response and coagulopathy is not known and therefore constitutes the aim of the present study.MethodsOne hundred sixty eight patients were studied as part of a prospective cohort study of severe trauma patients admitted to a single Level 1 Trauma center. Blood was drawn within 10 minutes of arrival to the emergency room before the administration of any fluid resuscitation. HMGB1, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, von Willebrand Factor (vWF), angiopoietin-2 (Ang-2), Prothrombin time (PT), prothrombin fragments 1+2 (PF1+2), soluble thrombomodulin (sTM), protein C (PC), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) and D-Dimers were measured using standard techniques. Base deficit was used as a measure of tissue hypoperfusion. Measurements were compared to outcome measures obtained from the electronic medical record and trauma registry.ResultsPlasma levels of HMGB1 were increased within 30 minutes after severe trauma in humans and correlated with the severity of injury, tissue hypoperfusion, early posttraumatic coagulopathy and hyperfibrinolysis as well with a systemic inflammatory response and activation of complement. Non-survivors had significantly higher plasma levels of HMGB1 than survivors. Finally, patients who later developed organ injury, (acute lung injury and acute renal failure) had also significantly higher plasma levels of HMGB1 early after trauma.ConclusionsThe results of this study demonstrate for the first time that HMGB1 is released into the bloodstream early after severe trauma in humans. The release of HMGB1 requires severe injury and tissue hypoperfusion, and is associated with posttraumatic coagulation abnormalities, activation of complement and severe systemic inflammatory response

Presidential Election Campaigns and American Democracy: The Relationship Between Communication Use and Normative Outcomes

There is very little research about the relative influence of campaign communication forms or venues on normative outcomes concerning the extent to which campaign communication promotes or degrades basic democratic values. This investigation assesses the relative impact of 17 communication forms on three normative outcomes: political expertise, which embodies people’s awareness, knowledge, and interest in politics; attitude about the process used to elect candidates; and likelihood of participating in the political process. Data are based on results of two national surveys conducted in different phases of the 2004 presidential campaign. Hierarchical regression analyses are used to evaluate the relative influence of the 17 communication forms on normative outcomes, controlling for sociodemographic variables.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Health Care Sustainability Science: The Next Frontier for Clinician Scientists in Anesthesiology

For over 30 years, the Foundation for Anesthesia Education and Research (FAER) has been dedicated to developing the next generation of physician-scientists in anesthesiology. Funding mechanisms span medical students, residents, fellows and early career faculty members. FAER Research Fellowship Grants (RFG), Mentored Research Training Grants (MRTG), Research in Education Grants (REG) and Transition to Independence Grants (TIG) support anesthesiologists to develop the skills and gather the preliminary data they need to become independent, federally funded investigators in basic science, clinical, translational, health services and education research. An important decision when embarking on a research career is the selection of a focused research area. Choosing research questions that are personally inspiring and are recognized as important by the specialty and funding agencies is an important first step. An emerging field of research that has broad impact across multiple disciplines and will be increasingly valued by funding agencies is the environmental and public health impact of anesthetic practice. In turn, this area of study is part of a larger discipline: health care sustainability research

Plastics in Health Care: Crisis or Opportunity?

Plastic is one of the most consequential inventions of the 20th century. Presently, over 335 million tons of plastic is produced in the world each year.1 Plastics are used broadly throughout healthcare because they are light weight, waterproof, and perceived as low cost compared to reusable goods. As a result, healthcare facilities in the United States generate around one million tons of plastic waste per year, the majority (85 percent) of which is non-infectious and potentially suitable for recycling.2 Many of the plastics used in healthcare applications have health and environmental impacts associated with their use and disposal. Dioxin, a by-product of polyvinyl chloride (PVC), is a known carcinogen. Plastic additives such as phthalates are ionically bound to the plastic matrix and leach out, especially when contacting heat and lipids.3 Phthalates have been found in food, drinking water, and in urine after single exposures to intravenous fluids.4 Phthalates disrupt endocrine function and have been associated with negative effects on liver, spleen, bone formation, body weight, and asthma.3 Plastic persists in the environment for decades, often contaminating the marine ecosystem, food chain, and water sources. Sadly, it is projected that there will be more plastic by weight in our oceans than there are fish by 2050.

Inhaled Anesthetic 2020 Challenge: Reduce Your Inhaled Anesthetic Carbon Emissions by 50%!

Climate change has been named the number-one public health threat of the 21st century. An estimated 150,000 deaths occur annually worldwide due to climate change-mediated health hazards such as extreme weather events, poor air quality, food and water-borne illnesses, vector-borne disease, food and water insecurity, and social instability. Loss of an additional 250,000 lives per year is projected to occur between 2030-2050 from climate change,1 and critical earth systems will be further disrupted in decades to come unless significant action to mitigate emissions is taken urgently.2 The Intergovernmental Panel on Climate Change (IPCC) Special Report concluded that anthropogenic CO2 emissions need to fall by 45% by 2030 compared to pre-industrial baselines, and reach “net zero” by 2050, to limit warming to an average increase of 1.5°C by 2100 in order to avert some of the worst planetary health outcomes. IPCC Co-Chair Debra Roberts, Ph.D., stated that “the next few years are probably the most important in all of human history.”

Early release of high mobility group box nuclear protein 1 after severe trauma in humans: role of injury severity and tissue hypoperfusion.

IntroductionHigh mobility group box nuclear protein 1 (HMGB1) is a DNA nuclear binding protein that has recently been shown to be an early trigger of sterile inflammation in animal models of trauma-hemorrhage via the activation of the Toll-like-receptor 4 (TLR4) and the receptor for the advanced glycation endproducts (RAGE). However, whether HMGB1 is released early after trauma hemorrhage in humans and is associated with the development of an inflammatory response and coagulopathy is not known and therefore constitutes the aim of the present study.MethodsOne hundred sixty eight patients were studied as part of a prospective cohort study of severe trauma patients admitted to a single Level 1 Trauma center. Blood was drawn within 10 minutes of arrival to the emergency room before the administration of any fluid resuscitation. HMGB1, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, von Willebrand Factor (vWF), angiopoietin-2 (Ang-2), Prothrombin time (PT), prothrombin fragments 1+2 (PF1+2), soluble thrombomodulin (sTM), protein C (PC), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) and D-Dimers were measured using standard techniques. Base deficit was used as a measure of tissue hypoperfusion. Measurements were compared to outcome measures obtained from the electronic medical record and trauma registry.ResultsPlasma levels of HMGB1 were increased within 30 minutes after severe trauma in humans and correlated with the severity of injury, tissue hypoperfusion, early posttraumatic coagulopathy and hyperfibrinolysis as well with a systemic inflammatory response and activation of complement. Non-survivors had significantly higher plasma levels of HMGB1 than survivors. Finally, patients who later developed organ injury, (acute lung injury and acute renal failure) had also significantly higher plasma levels of HMGB1 early after trauma.ConclusionsThe results of this study demonstrate for the first time that HMGB1 is released into the bloodstream early after severe trauma in humans. The release of HMGB1 requires severe injury and tissue hypoperfusion, and is associated with posttraumatic coagulation abnormalities, activation of complement and severe systemic inflammatory response