For patients in the ICU with coagulopathy and associated World Health Organization (WHO) grade 3 or 4 bleeding, which hemostatic therapy -- plasma versus 4-factor prothrombin complex concentrates -- is preferred?
Goal 2: Reduce Human Disease
What innovative methodologies applicable to small cohorts and rare outcomes can better ensure the success of clinical and implementation studies in the rare diseases affecting heart, lung, blood, and sleep?
Can we identify (and target) more precise mechanisms underlying age-related diseases such as idiopathic pulmonary fibrosis?
What are systems-based approaches to better define disease endotypes and develop more effective therapies, especially in multiple chronic conditions?
Does the addition of albumin to fluid conservative management of ALI (ARDSnet FACTT trial protocol, Wiedemann et al) further shorten ventilator time and/or improve survival?
At what INR threshold does prophylactic plasma transfusion, in non-bleeding critically ill patients who are planned to undergo an invasive procedure, prevent bleeding complications and improve patient outcomes?
NIH has a major initiative in Precision Medicine, including whole genome sequencing. In contrast to cancer, mutations with large clinical effects are expected to be uncommon in most non-malignant chronic diseases, such as asthma and COPD. Other data types such as gene expression, biomarkers, and micro RNAs must be combined with clinical and imaging phenotyping to advance Precision medicine in non-malignant lung diseases. ...more »
Alk 1 or Endoglin deficient endothelial cells promote recruitment of monocytes/macrophages and differentiation of them can play a critical role in development of arteriovenous malformations. Will targeting macrophage recruitment or activation instead of angiogenesis result in greater understanding leading to new therapeutic targets to control disease?
Gasotransmitters, such as nitric oxide, hydrogen sulfide, carbon monoxide, and hydrogen, have emerged as potent mediators of cardiovascular and lung cellular and molecular pathophysiology. While the physiological importance of these agents is becoming clearer, studies of gasotransmitters continue to suffer from several limitations such as formation, detection, metabolism, and molecular and cellular mechanistic insights. ...more »
Chronic stress is a risk factor for obesity, cardiovascular disease, atherosclerosis, and stroke. Glucocorticoid hormones are elevated chronically in stressed conditions and are thought to contribute to the pathogenesis of metabolic and cardiovascular disease. Despite strong evidence for this, non-pharmacologic therapies to reduce stress are not currently part of standard care for the prevention or treatment of metabolic ...more »
There is a need to recognize and study the interdependencies between the brain/peripheral nervous system and the heart/vascular systems in health and disease to develop interventions to detect, treat, and prevent cardiovascular disease.