Showing 5 ideas for tag "metabolic"

Goal 2: Reduce Human Disease

Intervening on Metabolic Derangements Induced by Allogeneic Hematopoietic Stem Cell Transplantation

Can standardized screening, pharmacological/behavioral prevention, and optimized treatment of metabolic complications after allogeneic hematopoietic stem cell transplantation improve outcomes and decrease transplant-related morbidity and mortality?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

The development of type 2 diabetes mellitus (DM) is a significant complication for long-term cancer survivors including patients treated with allogeneic hematopoietic stem cell transplantation (HCT). New onset, post-transplant DM (PTDM) occurs in up to 60% of HCT recipients, often precedes the development of acute GVHD, and negatively impacts survival. Type 2 DM is a complex disorder characterized by hyperglycemia, insulin resistance, and relative insulin insufficiency. The transition from insulin resistance to diabetes is associated with an inflammatory milieu characterized by the accumulation of IFN-γ secreting T cells (Th1 cells) and depletion of immunosuppressive Foxp3+ regulatory T cells in visceral organs and adipose tissue. Similarities exist between the immunology of insulin resistance and GVHD. However, the initiating events and mechanisms that culminate in PTDM development remain understudied, and formal recommendations for screening and treatment are lacking. All pregnant women undergo screening for diabetes, which complicates 2-10% of pregnancies in the United States. About 30% of renal transplant patients develop diabetes (NODAT), and current recommendations include weekly fasting blood glucose measurements. No such recommendations exist for HCT recipients, of whom up to 60% will develop de novo PTDM. Through clinical investigation, effective strategies for screening, preventing, and optimally treating PTDM can be developed and HCT outcomes improved.

Feasibility and challenges of addressing this CQ or CC

It is time to make up for lost (scientific) ground. It will require the efforts of a large network like the BMT-CTN to quickly address problems, answer important scientific questions, and raise awareness for a frequent but understudied complication following HCT.

Name of idea submitter and other team members who worked on this idea Brian Engelhardt and Madan Jagasia, Vanderbilt University

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14 net votes
23 up votes
9 down votes
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Goal 3: Advance Translational Research

Translation of an intervention to reduce sudden cardiac death

There is a need to identify and to develop pharmaceutical interventions for patients at risk for sudden cardiac death (SCD).

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Markedly reduce sudden cardiac death in high populations. Lead to a new pharmacologic paradigm for preventing lethal cardiac arrhythmias.

Feasibility and challenges of addressing this CQ or CC

Investigators have already demonstrated in animal models of SCD that inhibition of mitochondrial Na/Ca-exchange is associated with a reduction in ventricular arrhythmias and SCD without a change in corrected-QTC.
Using a novel guinea pig model of heart failure and sudden cardiac death (SCD), researchers (Circ Res. 2014 Jun 20;115(1):44-54) have demonstrated that inhibition of the mitochondrial sodium-calcium exchanger prevents SCD. In people, SCD accounts for 170,000 to 450,000 deaths per year in the US. Basic research focused on identifying cardiac ion channel inhibitors have failed to results in antiarrhythmic drugs that prevent SCD. And although clinical research has thus far failed to identify individuals at risk of suffering a SCD in the general population, subpopulations (for example, those with a low ejection fraction months after suffering a myocardial infarction) have been identified that are at high risk. If an effective pharmaceutical intervention was developed that reduces SCD, deaths in these populations would be markedly reduced. Strategies need to be developed to translate this promising basic science finding into saving lives.

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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5 net votes
19 up votes
14 down votes
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Goal 2: Reduce Human Disease

Chronic stress and cardiovascular/metabolic disease

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 »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

Understanding how stress contributes to cardiovascular and metabolic disease could lead to additional therapies targeting stress reduction for their prevention. The long-term impact of studies to establish and reduce the negative impact of stress on health could include better outcomes for stress reduction programs at work and strategies to reduce stress at home.

Feasibility and challenges of addressing this CQ or CC

Clinical trials to evaluate the efficacy of non-pharmacologic therapies targeting stress reduction are already feasible including such interventions as exercise, improved sleep, mindfulness, and social interaction. Some of these have been evaluated on a small scale, but future clinical trials should include long-term follow up and be sufficiently populated for their outcomes to influence patient care. Pharmacologic therapies targeting the stress system have not yet emerged as options for prevention and treatment, and pose a greater challenge. They will require investigation into the mechanisms of stress effects on chronic disease as well as intelligent drug design to minimize systemic side effects.

Name of idea submitter and other team members who worked on this idea Endocrine Society

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11 net votes
12 up votes
1 down votes
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Goal 2: Reduce Human Disease

Imaging indicators of metabolic syndrome and cardiopulmonary disease

Critical Challenge

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Obesity and metabolic syndrome affect a large portion of the population and affects multiple organ systems. Identifying obesity phenotypes by imaging will impact the significant healthcare issue presented by MetS and could provide a reliable, non-invasive index of disease severity, guide prevention and intervention response.

Feasibility and challenges of addressing this CQ or CC

Metabolic syndrome, abnormal metabolism, may be potentially linked to obesity and cardiopulmonary disease. Theories exist but are in need of clarification. The relationship between metabolic syndrome and multiple other diseases including chronic obstructive lung disease, coronary atherosclerosis, and obesity warrants further investigation and can be elucidated through imaging. Advances in computed tomography (CT) and magnetic resonance imaging (MR) enable assessment of the cardiopulmonary manifestations, with promising MR techniques to complement high-resolution imaging data achievable with chest CT and coronary CT angiography. Assessment of CT and MR techniques in combination with three-dimensional quantitative analysis of manifestations of metabolic syndrome such as fat deposits derived from different adipocytes (white fat versus brown fat) such as in the subcutaneous, visceral, epicardial, and perivascular regions is feasible with current technology and may enable differentiation of those with varying risks of cardiovascular and pulmonary disease. The association of imaging parameters, metabolic syndrome, and associated diseases are in need of investigation, and knowledge gained may prove crucial for identifying those at risk for metabolic syndrome and at higher risk for complications in the large population of our country affected by obesity.

Name of idea submitter and other team members who worked on this idea Society of Thoracic Radiology

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6 net votes
10 up votes
4 down votes
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Goal 1: Promote Human Health

Hypothermia and hemostasis after severe trauma

There is a need to employ new molecular tools to delineate the difference between beneficial and uncontrolled shock-induced hypothermia, because data on hypothermia and hemostasis are incomplete or lacking, especially on the duration, depth and type of hypothermia.

 

availability of targeted resource grant funding

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

improvement of survival with life threatening traumatic injuries with new metabolically modulating strategies, including "simple hypothermia", improved understanding of the relationship between ischemia and reperfusion, the role of inflammatory and metabolic pathways, definition and identification of appropriate targets for therapy, the role for mechanical devices, and relationship between timely application of hypothermia and rewarming.

Feasibility and challenges of addressing this CQ or CC

the tools and animal models are available to study hemostatic and metabolic modulation/hypothermia in traumatic injury
Trauma is the major cause of death in young individuals in the US, and globally, with uncontrolled hemorrhage representing the major cause of preventable deaths. Hypothermia, used in life threatening cardiovascular states, also holds enormous promise for application in traumatic injuries. Early deployment (pre-hospital) of novel protective metabolically modulating strategies to attenuate cellular injury from shock and reperfusion, such as hypothermia could be beneficial. However, the relationship between hypothermia in traumatic setting is complex, with data suggesting detrimental outcomes if it occurred spontaneously. In contrast, hypothermia induced in a controlled manner can protect tissues from ischemic injury.

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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-8 net votes
7 up votes
15 down votes
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