Showing 13 ideas for tag "syndrome"

Goal 3: Advance Translational Research

TREATMENT OF SEPSIS-MULTIPLE ORGAN DYSFUNCTION SYNDROME (MODS) UTILIZING APHERESIS BASED STRATEGIES

Sepsis, a systemic inflammatory response to infection, is the most common cause of death in non-cardiac intensive care units. The incidence and severity of sepsis have increased over the last two decades. With advances in supportive care, sepsis carries a mortality that averages 17%, however, this figure increases to 50 - 80% in Multiple Organ Dysfunction Syndrome (MODS), defined as failure of 3 or more organ systems.... 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

Despite many attempts, therapeutic trials using pharmacologic agents to interrupt specific pathways of inflammation and coagulation have been unsuccessful. The failed targeted therapies include the administration of corticosteroids, monoclonal antibodies to TNF, soluble TNF receptor, antithrombin (AT), activated protein C, and tissue factor pathway inhibitor. Because it is non-selective, plasma exchange has the potential to remove deleterious mediators and restore anti-inflammatory/anticoagulant factors consumed in sepsis/MODS. There is evidence that some of the implicated mediators of sepsis can be effectively removed by plasma exchange, eg, TNF alpha and endotoxin. In addition, the normal regulatory molecules consumed during the systemic inflammatory process, such as AT, proteins C and S, and ADAMTS-13 would be replaced, which may influence the pathophysiology of MODS/sepsis. However, the mechanism of action of plasma exchange, whether removal of inflammatory mediators of sepsis or modulation of the later consequences of MODS such as sustained endothelial activation, remains unclear at the present time. Other apheresis based strategies also have been attempted but their results also require confirmation by well-designed clinical trials to answer the question of their value in treatment of sepsis.
Development of apheresis strategies which address the pathophysiology of sepsis and identify responsive patient populations would have a great societal value

Feasibility and challenges of addressing this CQ or CC

Feasibility: the large number of patients who develop sepsis provides for significant number of potential patients who can be enrolled. More sophisticated methods of enrollment may help as many patients are not capable of providing informed consent. Establishing an apheresis consortium and collaboration with intensive care physicians will be an important step in assuring appropriate accrual of patients. The availability of apheresis devices is likely to be high in the tertiary/quaternary care medical centers where these studies can be performed. Animal models of sepsis are being investigated and are necessary for studies evaluating pathophysiology; though some apheresis strategies can be moved to clinical studies without additional preclinical developments.

Challenges: Identification of the patient population which responds optimally to apheresis based strategies is critical to the development of a randomized clinical trial. One study has indicated that it would be the critically ill pediatric population; however, the critically ill adult population is the largest affected group). Given the equipoise of using apheresis based strategies in the treatment of sepsis/MODS, finding patients to randomize is unlikely to be difficult. Other potential challenges include the cost of developing randomized clinical trials using apheresis, competition with other pharmacology based strategies, center bias, and the timing for initiation of the apheresis.

Name of idea submitter and other team members who worked on this idea Zbigniew M. Szczepiorkowski; Joseph Kiss, Ed Wong on behalf of ASFA

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97 net votes
115 up votes
18 down votes
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Goal 2: Reduce Human Disease

Hypoxia, acute chest syndrome and sickle cell disease

What markers in sickle cell disease can predict hypoxia after acute chest syndrome or pneumonia?

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 that sickle cell disease has a character of depriving oxygen, is there any predicators that can tell if a child will have hypoxia after experiencing acute chest syndrome or pneumonia.

Name of idea submitter and other team members who worked on this idea Sickle Cell Warriors, Inc. community members

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32 net votes
41 up votes
9 down votes
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Goal 2: Reduce Human Disease

The treatment of asthma in patients with SCD prevents the development of ACS and VOS.

Does the aggressive treatment of asthma prevent the developement of acute chest syndrome (ACS) and vaso-occlusive syndrome (VOS) in patients with sickle cell disease (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

Improvement of health for persons with SCD.
Decreased hospitalizations and use of health resources.
Better understanding of the role of bronchospastic/inflammatory airway disease and hypoxemia as causes of acute chest syndrome and VOC.

Feasibility and challenges of addressing this CQ or CC

Feasible but stumbling block could be enrollment of patients since many patients with SCD are not seen by asthma specialists. Study could be a multicenter study with two hospitals in one major city and in one center, patients with SCD receive usual care and at another center they receive aggressive treatment and monitoring of their lung disease.

Name of idea submitter and other team members who worked on this idea Scott Schroeder

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13 net votes
27 up votes
14 down votes
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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 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 2: Reduce Human Disease

Is there a Biomarker for the Pulmonary Fibrosis of HPS?

Hermansky-Pudlak Syndrome is characterized by a bleeding disorder as well as pulmonary fibrosis. Invasive procedures such as a lung biopsy are contraindicated due to bleeding and bronchoscopy is not without risk. Finding a biomarker would reduce the necessity for more invasive data collection while improving outcomes.

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

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2 net votes
3 up votes
1 down votes
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Goal 3: Advance Translational Research

Obesity in special needs populations: Congenital heart disease

What are effective prevention and treatment strategies for populations with special needs, such as those with congenital heart disease, Down syndrome and preterm-born, to maintain a healthy weight?

Are there successful strategies derived from "normal" populations that could be effectively applied to these populations?

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

Details on the impact of addressing this CQ or CC

Children and individuals with special health conditions or needs are often excluded from participating in obesity treatment and prevention studies at the individual, group and community level. By answering this question, we would anticipate improving health, reducing future CV risks, increasing quality of life and decreasing already substantial healthcare costs in special needs populations.

Feasibility and challenges of addressing this CQ or CC
  1. We are beginning to understand which strategies appear effective in healthy overweight/obese populations, which could be leveraged for studies and interventions in special populations. 2. Adequate populations exist to address this CC: There are now more adults than children living with congenital heart disease, nearly 50% overweight or obese. Among these, individuals with Down syndrome are disproportionately overweight and have metabolic dysfunction. Preterm-born adults are more likely to be overweight/obese, have increased BP and other CV risks compared to term-born adults. 3. The Research Plan for Down Syndrome (NICHD) lists "obesity" in its short term research objectives.

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

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-24 net votes
12 up votes
36 down votes
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Goal 3: Advance Translational Research

Detection of inflammatory monocytes as a biomarker of CVD

Coronary artery disease (CAD), of which atherosclerosis is a major contributor, costs the United States $108.9 billion each year. While a number of conventional risk factors such as smoking, diabetes and hypertension have been associated with CAD, their predictive performance is poor in the prevention of acute coronary syndrome (ACS). Despite the prevalence of ACS in our society, there are currently no molecular biomarkers... more »

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

Details on the impact of addressing this CQ or CC

Need more opportunities to put forth innovative diagnostic and therapeutic solutions than currently vetted through the CTSC process.
We have developed the Artery-on-a-chip (A-chip), currently in a research tool format, which accurately measures the extent of inflammatory monocyte activation in a whole blood sample by shearing it along a molecular sensor and enumerating monocyte capture.

Name of idea submitter and other team members who worked on this idea Scott I Simon, Greg Foster, Ehrin Armstrong

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-6 net votes
8 up votes
14 down votes
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Goal 3: Advance Translational Research

Increasing the adoption of low tidal volume ventilation in ARDS patients

How can we use implementation science to increase the adoption of low-tidal volume ventilation in patients with acute respiratory distress syndrome (ARDS)?

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 tidal volume ventilation has been shown to significantly reduce mortality in ARDS patients (from 40% to 31% in the ARMA trial published in NEJM in 2000), but it is inconsistently adopted (frequently with rates <50% in both community and academic settings). Improving adherence has the potential to significantly improve mortality in patients with ARDS.

Feasibility and challenges of addressing this CQ or CC

Given the rapid growth and interest in the field of implementation science over the past several years, addressing this question is now feasible.

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-10 net votes
2 up votes
12 down votes
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Goal 2: Reduce Human Disease

Sex and Race Differences in Replacement Lung Surfactant Efficacy

Baby boys and girls can respond quite differently to replacement lung surfactants given in response to neonatal respiratory distress syndrome. There are also variations in efficacy between babies of different races, in addition to the generally increased risk of NRDS in minority populations overall to lack of prenatal care or access to neonatal intensive care units. Increasing the availability of surfactant treatment... more »

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

Details on the impact of addressing this CQ or CC

Infant mortality varies dramatically across racial and economic status, and prematurity and its accompanying diseases is one important aspect of this discrepancy. Replacement surfactant therapy dramatically decreased the infant mortality rate when it was originally initiated, but certain populations are less served, and variations in efficacy of treatment are poorly understood. New methods of delivering surfactant, such as aerosols combined with CPAP and a better understanding of the properties of surfactant might be two ways to address this issue.

Feasibility and challenges of addressing this CQ or CC

This challenge requires a broad, multidisciplinary approach including engineers, neonatologists and biophysicists to produce the necessary materials and tools to properly synthesize and deliver surfactant. A larger challenge is to simplify the process enough that surfactant replacement therapy could be introduced into less developed countries where prematurity is of epidemic proportion.

Name of idea submitter and other team members who worked on this idea Joe Zasadzinski

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-7 net votes
3 up votes
10 down votes
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Goal 3: Advance Translational Research

Screening the work force for genetic arrhythmias

Is anyone in your family at risk for a potentially lethal genetic arrhythmia? 4000 young people die each year because they bear a genetic mutation that makes them susceptible to a sudden fatal arrhythmia. The symptoms are easy to identify and awareness of these symptoms would help unsuspecting families.

 

It is estimated that one of these syndromes (LQTS) is 3 times more common in the US than childhood leukemia.

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

Details on the impact of addressing this CQ or CC

There are 3 simple warning signs for families bearing dominant mutations that could lead to arrhythmia and sudden death. These are unexplained fainting or seizure during exercise or startle, an unexplained sudden death of a young family member, chest pain and/or shortness of breath during exercise. A simple questionnaire of all families with children entering school or any athlete signing up for a sport, or any adult entering the work force would help identify potential family members at risk for these genetic arrythmias.

Feasibility and challenges of addressing this CQ or CC

A simple questionnaire of all families with children entering school or any athlete signing up for a sport, or any adult entering the work force would help identify potential family members at risk for these genetic arrythmias. Such potential patients could then be further screening by a EKG and a consult with a cardiologist.

Name of idea submitter and other team members who worked on this idea Andy Golden

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-10 net votes
2 up votes
12 down votes
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