John R. Hess

Bio: John R. Hess is an academic researcher from University of Washington. The author has contributed to research in topics: Blood transfusion & Resuscitation. The author has an hindex of 61, co-authored 318 publications receiving 17603 citations. Previous affiliations of John R. Hess include Australian Red Cross Blood Service & University of Cincinnati.

Transfusion of plasma, platelets, and red blood cells in a 1: 1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: The PROPPR randomized clinical trial

Abstract: Importance Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher blood product ratios (plasma, platelets, and red blood cells), defined as damage control resuscitation, has been associated with improved outcomes; however, there have been no large multicenter clinical trials. Objective To determine the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio. Design, Setting, and Participants Pragmatic, phase 3, multisite, randomized clinical trial of 680 severely injured patients who arrived at 1 of 12 level I trauma centers in North America directly from the scene and were predicted to require massive transfusion between August 2012 and December 2013. Interventions Blood product ratios of 1:1:1 (338 patients) vs 1:1:2 (342 patients) during active resuscitation in addition to all local standard-of-care interventions (uncontrolled). Main Outcomes and Measures Primary outcomes were 24-hour and 30-day all-cause mortality. Prespecified ancillary outcomes included time to hemostasis, blood product volumes transfused, complications, incidence of surgical procedures, and functional status. Results No significant differences were detected in mortality at 24 hours (12.7% in 1:1:1 group vs 17.0% in 1:1:2 group; difference, −4.2% [95% CI, −9.6% to 1.1%]; P = .12) or at 30 days (22.4% vs 26.1%, respectively; difference, −3.7% [95% CI, −10.2% to 2.7%]; P = .26). Exsanguination, which was the predominant cause of death within the first 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs 14.6% in 1:1:2 group; difference, −5.4% [95% CI, −10.4% to −0.5%]; P = .03). More patients in the 1:1:1 group achieved hemostasis than in the 1:1:2 group (86% vs 78%, respectively; P = .006). Despite the 1:1:1 group receiving more plasma (median of 7 U vs 5 U, P P Conclusions and Relevance Among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio did not result in significant differences in mortality at 24 hours or at 30 days. However, more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group, no other safety differences were identified between the 2 groups. Trial Registration clinicaltrials.gov Identifier:NCT01545232

Damage control resuscitation: Directly addressing the early coagulopathy of trauma

Abstract: : Rapid progress in trauma care occurs when the results of translational research are promptly integrated into clinical practice. Experience with a high volume of severely injured casualties expedites the process. Historically, these conditions have converged during times of conflict, improving the care of combat casualties and subsequently that of civilian trauma patients. In the most severely injured casualties, we know that when the lethal triad of hypothermia, acidosis, and coagulopathy are present, death is imminent. Current teaching is to avoid reaching these conditions by using damage control surgery. However, conventional resuscitation practice for damage control focuses on rapid reversal of acidosis and prevention of hypothermia, and surgical techniques focus on controlling hemorrhage and contamination. Direct treatment of coagulopathy has been relatively neglected, viewed as a byproduct of resuscitation, hemodilution, and hypothermia, and delayed by blood banking logistics. Damage control resuscitation addresses the entire lethal triad immediately upon admission to a combat hospital. By demonstrating that in the severely injured the coagulopathy of trauma is present at admission, recent studies have brought back to light the importance of treating this disorder at an earlier stage. Reports of lactated Ringer s solution and normal saline increasing reperfusion injury and leukocyte adhesion lead one to conclude that the standard crystalloid based resuscitation guidelines in pre hospital trauma life support (PHTLS) and advanced trauma life support (ATLS) may worsen the presenting acidosis and coagulopathy in severely injured trauma patients, and possibly increase ARDS, SIRS, and MOF. The safety of withholding PRBCs in hemodynamically stable patients has been demonstrated,18 and the risks associated with blood transfusion are well described.

The coagulopathy of trauma: a review of mechanisms.

Abstract: Background: Bleeding is the most frequent cause of preventable death after severe injury. Coagulopathy associated with severe injury complicates the control of bleeding and is associated with increased morbidity and mortality in trauma patients. The causes and mechanisms are multiple and yet to be clearly defined. Methods: Articles addressing the causes and consequences of trauma-associated coagulopathy were identified and reviewed. Clinical situations in which the various mechanistic causes are important were sought along with quantitative estimates of their importance. Results: Coagulopathy associated with traumatic injury is the result of multiple independent but interacting mechanisms. Early coagulopathy is driven by shock and requires thrombin generation from tissue injury as an initiator. Initiation of coagulation occurs with activation of anticoagulant and fibrinolytic pathways. This Acute Coagulopathy of Trauma-Shock is altered by subsequent events and medical therapies, in particular acidemia, hypothermia, and dilution. There is significant interplay between all mechanisms. Conclusions: There is limited understanding of the mechanisms by which tissue trauma, shock, and inflammation initiate trauma coagulopathy. Acute Coagulopathy of Trauma-Shock should be considered distinct from disseminated intravascular coagulation as described in other conditions. Rapid diagnosis and directed interventions are important areas for future research.

Reactive oxygen species activate the HIF-1alpha promoter via a functional NFkappaB site.

Abstract: Objective— Reactive oxygen species have been implicated as signaling molecules modulating the activity of redox-sensitive transcription factors such as nuclear factor kappa B (NF-κB). Recently, the transcription factor hypoxia-inducible factor-1 (HIF-1), known to mediate gene expression by hypoxia, has been found to be also activated by nonhypoxic factors in a redox-sensitive manner. We therefore aimed to elucidate the link between these 2 important redox-sensitive transcription factors. Methods and Results— In pulmonary artery smooth muscle cells, reactive oxygen species generated either by exogenous H2O2 or by a NOX4-containing NADPH oxidase stimulated by thrombin activated or induced NF-κB and HIF-1α. The reactive oxygen species-mediated HIF-1α induction occurred on the transcriptional level and was dependent on NF-κB. Transfection experiments with wild-type or mutant HIF-1α promoter constructs revealed the presence of a yet unidentified NF-κB binding element. Gel shift analyses and chromatin immunoprecipitation verified binding of NF-κB to this site. Furthermore, reactive oxygen species enhanced expression of plasminogen activator inhibitor-1, which was prevented by dominant-negative IκB or mutation of the HIF-1 binding site within the plasminogen activator inhibitor-1 promoter. Conclusion— These findings show for the first time to our knowledge that reactive oxygen species directly link HIF-1α and NF-κB, implicating an important pathophysiological role of this novel pathway in disorders associated with elevated levels of reactive oxygen species.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Medscape

Abstract: Secret History: Return of the Black Death Channel 4, 7-8pm In 1348 the Black Death swept through London, killing people within days of the appearance of their first symptoms. Exactly how many died, and why, has long been a mystery. This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale. And they ask, what might be coming next?

Guidelines for the Management of Spontaneous Intracerebral Hemorrhage. A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

Abstract: Purpose— The aim of this guideline is to present current and comprehensive recommendations for the diagnosis and treatment of acute spontaneous intracerebral hemorrhage. Methods— A formal literature search of MEDLINE was performed. Data were synthesized with the use of evidence tables. Writing committee members met by teleconference to discuss data-derived recommendations. The American Heart Association Stroke Council’s Levels of Evidence grading algorithm was used to grade each recommendation. Prerelease review of the draft guideline was performed by 6 expert peer reviewers and by the members of the Stroke Council Scientific Statements Oversight Committee and Stroke Council Leadership Committee. It is intended that this guideline be fully updated in 3 years’ time. Results— Evidence-based guidelines are presented for the care of patients presenting with intracerebral hemorrhage. The focus was subdivided into diagnosis, hemostasis, blood pressure management, inpatient and nursing management, preventing medical comorbidities, surgical treatment, outcome prediction, rehabilitation, prevention of recurrence, and future considerations. Conclusions— Intracerebral hemorrhage is a serious medical condition for which outcome can be impacted by early, aggressive care. The guidelines offer a framework for goal-directed treatment of the patient with intracerebral hemorrhage.