Goal 2: Reduce Human Disease

Transplant to Cure Older Adults with Hematologic Malignancy-Removing the Blindfold

While transplant for patients 60 and older for high-risk hematologic malignancies has increased and observational data are promising, the risks and benefits of translant versus non-transplant remain largely unknown. We now have the tools and mechanisms to remove the blindfold! The NHLBI should support the cooperative groups in conjunction with the BMT-CTN to establish a common framework for transplant trials in older ...more »

Submitted by (@aartz0)

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

Details on the impact of addressing this CQ or CC :

Hematologic malignancies are more common and less treatable in older patients. This trend will contine as the number and proportion of older people in society increases. Older patients are frequently treated but rarely on studies. The availability of haploidentical and cord donor sources, better supportive care, and more tolerable regimens permits transplant to be widely accessible and utilized.

 

A critical question for the entire field of hematologic malignancies is determing the risks and benefits of allogeneic transplant for older adults. This question is posed across the country, every day by every patient and physician struggling to treat older adults with hematologic malignancies. The confluence of molecular and cytogenetic disease markers and novel measures of patient health should permit identifying those most likely to be cured and those least likely to benefit. Such data will ultimately inform the next generation of transplant trials in this population.

Feasibility and challenges of addressing this CQ or CC :

The number of patients with any of these diseases (e.g., AML, MDS, NHL and perhaps ALL) who are 60 years and older is significant. The challenge is to develop a coordinated effort to prospectively capture disease and patient health data to answer which subgroups benefit or do not.

Methods to capture patient health status have already been developed through a standardized Geriatric Assessment used in the Alliance and other studies. Most of the survey can be done electronically by a patient or by telephone. Disease based molecular markers have emerged as standard measures within cooperative group studies to augment cytogenetic and morphologic classification.

 

Ensuring cooperative groups develop uniform design and data may be difficult. Yet investigators gain much and lose little by standardizing the data capture of what already occurs (patients moving to transplant on hematologic malignancy trials).

 

Another challenge is to develop standardized measures after transplant beyond survival such as function free survival and quality of life that are patient centered. Electronic tools to capture data, especially for non-transplant patients, will greatly reduce this burden.

Name of idea submitter and other team members who worked on this idea : Andrew Artz

Voting

20 net votes
36 up votes
16 down votes
Active

Goal 2: Reduce Human Disease

In pulmonary arterial hypertension (PAH), how can right ventricular function be improved in the setting of increased afterload

Pulmonary arterial hypertension (PAH) is a complex, progressive condition characterized by high blood pressure in the lungs and restriction of flow through the pulmonary arterial system. Significant improvements have been made in medical management with through approved pulmonary vasodilator therapies. However, long-term right ventricular afterload reductions have still not yet been achieved. The process by which the ...more »

Submitted by (@katherinek)

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 of many components of the PAH disease state have evolved significantly in the past thirty years. When initially described by an NIH registry, in a time where pulmonary transplantation was the only treatment for PAH, the average life expectancy of PAH patients was estimated to be 2.8 years. Since then, 12 PAH-targeted therapies have been approved by the FDA; these therapies primarily act by dilating the pulmonary arteries in order to allow blood to flow easier through the pulmonary vascular system. Despite these advances and complex therapies, long-term afterload reduction is not achievable in most PAH patients. Patients continue to die from right ventricular failure, highlighting the important relationship of the pulmonary arterial system and right ventricle. Little is known about how and why the RV progresses from hypertrophy to full RV failure, the diagnostic signs indicating early RV failure, and how best to intervene to support the failing ventricle. Knowledge in this area is critical, however, as the RV is able to recover in many patients with severe PAH after lung transplantation. The relationship between the lung vasculature and cardiac function, and specifically a characterization of RV failure, was included as a research opportunity in the Strategic Plan for Lung Vascular Research in an NHLBI-ORDR Workshop Report (Erzurum S, et al. 2010).

Feasibility and challenges of addressing this CQ or CC :

The primary challenge of addressing this CQ on how right ventricular function can be improved in the setting of increased afterload is the comprehensive analysis and support that will need to be provided, spanning from basic to clinical science. To begin, strong support of biologic characterization of the right ventricle needs to be provided. The RV is distinctly different from the more comprehensively studied left ventricle (LV), and subsequently responds differently to changes in pressure, neurotransmitters, hormones, and pharmaceutical therapies to name only a few. However, when identified, these RV biologic distinctions can be further explored to develop a better understanding of RV failure and potential points of intervention.

Name of idea submitter and other team members who worked on this idea : Katherine Kroner, Michael Patrick Gray, PHA

Voting

65 net votes
72 up votes
7 down votes
Active

Goal 2: Reduce Human Disease

Molecular effects of ischemia and reperfusion

What is the impact of total body ischemia and reperfusion on coagulation, inflammation, and endothelial function?

Submitted by (@rebecca.lehotzky)

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

Name of idea submitter and other team members who worked on this idea : AHA Staff & Volunteers

Voting

-4 net votes
1 up votes
5 down votes
Active

Goal 3: Advance Translational Research

Comprehensive Assessment of Cardiovascular Physiology: Imaging of Structure, Function and Blood Flow

The development of cardiovascular disease is associated with changes in structure, function and blood flow within a complex and highly interconnected system. Current diagnostic tools focus on individual elements of the cardiovascular system and/or relatively simple parameters which do not reflect the true underlying pathophysiology. A novel multi-modular and multi-parametric approach based on new and promising imaging ...more »

Submitted by (@mmarkl)

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

Voting

1 net vote
1 up votes
0 down votes
Active

Goal 2: Reduce Human Disease

Long-term pulmonary function in survivors of critical illness

Pulmonary function is known to suffer during the early recovery phases from critical illness, but the long-term patterns of recovery and associated consequences are uncertain. In addition, the clinical and molecular determinants of progressive deterioration or recovery of pulmonary function remain unknown.

Submitted by (@greg.martin)

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

Name of idea submitter and other team members who worked on this idea : Society of Critical Care Medicine Executive Committee/Council

Voting

4 net votes
7 up votes
3 down votes
Active

Goal 2: Reduce Human Disease

Role of epigenetic mechanisms in cardiovascular disease

Are epigenetic changes the cause or the consequence of changes in cell function that contribute to cardiovascular disease? If they are the cause, what are the mechanisms that lead to changes and how do they impact disease pathogenesis? If the consequence, do they play any role in disease pathogenesis? What methods can be used to test if epigenetic changes play a causal role in disease pathogenesis? Thus far studies ...more »

Submitted by (@gko000)

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

Details on the impact of addressing this CQ or CC :

Although it is widely speculated that epigenetic control mechanisms play a critical role in disease pathogenesis, few if any studies, particularly in the CV field, have actually determined if and how epigenetic mechanisms result in functional changes in the plethora of cells that contribute to CV disease pathology. Moreover, there is a general lack of methods available to determine how specific epigenetic modifications, including histone modifications or DNA methylation of a given gene locus impacts gene expression and function of that cell. Rather, most studies have been limited to studying the effects of global alterations in chromatin structure, and/or studying global changes in epigenetic modifications average over the tens or hundreds of cell types and phenotypes within a complex tissue.

 

We must develop approaches to dissect the causal role of specific epigenetic modifications in controlling cell function in health and disease.

Feasibility and challenges of addressing this CQ or CC :

There are approaches evolving that enable one to do epigenomic edting in single cells but thus far they have not been done in the CV system, nor in vivo. They are feasible but will take a major investment to be successful.

 

Keep in mind that epigenetic mechanisms presumably regulate overall change in cell function as a consequence of exposure to disease promoting stimuli. Importantly, this is in response not only to the environmental milieu to which the cell is currently exposed, but an integral of past signals it and its predecessors experienced. Unlocking these control mechanisms will likely greatly advance our understanding of all disease processes, but particularly CV diseases which typically develop over years or decades.

Name of idea submitter and other team members who worked on this idea : Gary K Owens

Voting

21 net votes
28 up votes
7 down votes
Active

Goal 2: Reduce Human Disease

Cure COPD

How can the structure and function lost in COPD be restored?

Submitted by (@jsullivan)

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

Details on the impact of addressing this CQ or CC :

The tissue alterations in COPD and their physiologic consequences of those changes are reasonable well described. It is now clear that, like all organs, the lung can repair damaged tissue and that repair processed can be modulated. Strategies for assessing restoration of lost tissue structure and function should be developed, together with the development of clinical measures that can gauge progress of treatment.

Feasibility and challenges of addressing this CQ or CC :

Animal studies demonstrate that emphysema can be repaired, at least in some species. Several forms of airways disease in humans are also reversible. Studies of interventions to augment tissue repair are needed with the goal of applying them to clinical interventions.

Name of idea submitter and other team members who worked on this idea : COPD Foundation, COPDF MASAC

Voting

18 net votes
20 up votes
2 down votes
Active

Goal 1: Promote Human Health

Critical Windows in Early Development to Maximize Lung Health

Is there a critical window of growth and development for maximizing lung function?

Submitted by (@nhlbiforumadministrator)

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

Details on the impact of addressing this CQ or CC :

Low lung function during childhood tracks to early adulthood and contributes to early onset disease. Lung health promotion is needed, but we know little about what can enhance and protect human health during rapid phases of lung development in utero and growth postnatally to adulthood.

Feasibility and challenges of addressing this CQ or CC :

Researchers could turn their attention on healthy and “maximally” health populations (human and model organisms) to understand genetic and environmental exposures that influence lung function at upper ends of the spectrum (>2 SD from the mean).

Recent findings suggest that there is an urban-rural continuum of lung function in specific ethnic groups; and interventions with maternal dietary supplements can enhance lung function in offspring. These set the stage for further study on developing knowledge of early life events that can inform lung health promotion.

Voting

5 net votes
17 up votes
12 down votes
Active

Goal 1: Promote Human Health

Cardiac Engineering – Deciphering the Cardiome

To maintain cardiac health and prevent disease, there is a need to decipher the cardiome of cells and genes and use this knowledge (1) to better understand cardiac structure and function and (2) to engineer systems on the level of organs, organ systems, and the entire individual.

Submitted by (@nhlbiforumadministrator1)

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

Details on the impact of addressing this CQ or CC :

Improved CV health

Feasibility and challenges of addressing this CQ or CC :

new advances in study of the cardiome

Advances in in the sub-micro-world over the past several years have led to greater opportunities to better understand cells and genes. These new developments have and will continue to provide greater insight into understanding cardiac structure and function, which has and will likely to result in improved therapies for heart disease. The advances being made in science and technology have expanded the frontiers of cardiology as a result of important advances in micro-imagining and molecular diagnostic methods. These advances have transformed classical study of the macro-world of living human beings and the cardiac disease that afflict them.

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

Voting

-16 net votes
10 up votes
26 down votes
Active

Goal 1: Promote Human Health

The coupling of mechanical stress to biochemistry, molecular biology and electrophysiology

Cells aren’t beakers holding soluble reactants waiting to be mixed. Cells are structured objects where life forms as a flow of free energy between three pools: chemical, electrical and mechanical. Most papers in the literature ignore structure (except of Xray or EM of specific proteins) and almost all ignore the coupling of mechanics to the other pools. Cells cannot be studied with in vitro experiments. We can study single ...more »

Submitted by (@nhlbiforumadministrator1)

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

Details on the impact of addressing this CQ or CC :

If we learn how a third of all cellular energy is used we have a better chance of understanding the other 2/3.

Feasibility and challenges of addressing this CQ or CC :

See more at: http://grants.nih.gov/grants/guide/notice-files/NOT-HL-15-252.html#sthash.7xHiSbcd.dpuf

Name of idea submitter and other team members who worked on this idea : Dr. Frederick Sachs

Voting

9 net votes
29 up votes
20 down votes
Active

Goal 3: Advance Translational Research

Cellular & molecular effects of diabetes on the heart

Diabetes increases cardiovascular disease risk factors. Evidence suggests that diabetes alters contractile and electrical function of the heart, but little is known about the cellular and molecular basis for these changes.

Submitted by (@catherine.proenza)

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

Details on the impact of addressing this CQ or CC :

Develop more effective treatments for cardiovascular disease in patients with diabetes and metabolic syndrome.

Voting

21 net votes
36 up votes
15 down votes
Active

Goal 2: Reduce Human Disease

Developing techniques to monitor neurologic injury after cardiac arrest

Can techniques to monitor brain injury and recovery in post-cardiac arrest patients be developed to optimize post-cardiac arrest care and enable reliable neuroprognostication?

Submitted by (@rebecca.lehotzky)

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

Name of idea submitter and other team members who worked on this idea : AHA Staff & Volunteers

Voting

-1 net votes
2 up votes
3 down votes
Active