Showing 14 ideas for tag "inflammation"

Goal 2: Reduce Human Disease

Enhanced Pain Research in Sickle Cell Disease

There is a need for more enhanced pain research in order to help improve sickle cell disease patient outcomes and quality of life.

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

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Pain is the most common clinical manifestation of sickle cell disease (SCD) and accounts for a large proportion of emergency department visits and hospitalizations. Due to its impact on the patients’ quality of life, there is a need for more basic and clinical research studies focused on understanding the mechanisms of different pain syndromes as well as the role of neurotransmitters and inflammation in acute and chronic SCD pain. Also, comparative effectiveness studies in the management of chronic pain will be crucial in helping to improve the patients’ overall quality of life.

Name of idea submitter and other team members who worked on this idea Alice Kuaban on behalf of the American Society of Hematology (ASH)

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39 net votes
58 up votes
19 down votes
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Goal 2: Reduce Human Disease

The Use of Therapeutic Apheresis to Reduce Circulating Levels of Galectin-3 and other Cancer and Inflammation Promoting Factors

Inflammation plays roles in cancer initiation, promotion, and progression. Elevated circulating galectin-3 (Gal-3) protein and other cancer and inflammation promoting factors (CIPFs) such as C-reactive protein and VEGF are associated with tumorigenesis and may play causative roles. Plasma Gal-3 is a biomarker, prognosticator, and pathogenic mediator of diverse cancers and is emerging as a therapeutic target. Preliminary... more »

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

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Apheresis therapy in a clinical setting, both alone and in combination with conventional protocols, shows great potential to enhance treatment regimens, reduce dosage and side effects, improve drug deliver to target tissues, reduce long term treatment related morbidity and improve outcomes with significant benefits for patients with a broad range of cancer types and stages.

Feasibility and challenges of addressing this CQ or CC

The need for well designed, randomized clinical trials would be readily feasible with the appropriate IND. Grant support will be needed for further development of this concept, as well as to develop columns with more optimized and specific capabilities, in addition to clinical trials demonstrating efficacy.

Apheresis is highly underutilized and underfunded in the US, while Apheresis research and development is much more advanced and widely utilized in Europe and Asia.

Name of idea submitter and other team members who worked on this idea Isaac Eliaz, MD

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33 net votes
40 up votes
7 down votes
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Goal 2: Reduce Human Disease

Assess the true impact of sickle cell trait on cardiovascular health across then age spectrum

Sickle cell disease is now understood as a disease of inflammation in addition to abnormal red blood cells. It is likely persons with sickle cell trait are also negatively affected by the damage caused by inflammation. There is a significant racial disparity in hypertension, stroke, and chronic kidney disease. It remains unclear the degree to which sickle cell trait contributes to this disparity. It also remains unclear... more »

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

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Recent evidence in the United States emphasizes the possible health risks for individuals with HbAS including increased incidence
of renal failure and malignancy, thromboembolic disorders, splenic infarction as a high altitude complication, and exercise-related sudden death. Additional concerns include the increase risk of hypertension from endothelial scaring and additional vascular abnormalities. Early preventative therapies for persons with HbAS (sickle cell trait) could reduce the progression of cardiovascular disease in manny individuals if found to be of concern.

Feasibility and challenges of addressing this CQ or CC
  1. Several identified impediments to research of sickle cell trait have included under-representation of the African– American community in preclinical and translational research projects and limited study in health disparities research (Am J Hematol . 2012 March ; 87(3): 340–346).
  2. Ethical considerations in screening athletes and other individuals seeking labor intensive occupations for sickle cell trait
  3. The diagnosis of the carrier state for a genetic disease may be associated with serious health problems that can lead to widespread bioethical and social stigmatization and additional concerns including the increased need for testing and counseling

Name of idea submitter and other team members who worked on this idea Julie Kanter

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17 net votes
31 up votes
14 down votes
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Goal 2: Reduce Human Disease

Impact of lung remodeling on congestive heart failure progression

End stage congestive heart failure (CHF) causes intensive lung remodeling beyond the type-2 pulmonary hypertension. CHF induced lung remodeling includes profound lung fibrosis, lung vascular remodeling and lung inflammation. Understanding CHF-induced lung remodeling is also critical to understand the right ventricular failure. However, this area is largely unstudied. Regulating CHF-induced lung remodeling and the underlying... more »

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

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To deal end-stage CHF will need team efforts from heart, lung, blood and immunology.

Name of idea submitter and other team members who worked on this idea Yingjie Chen, Associate Professor, University of Minnesota

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13 net votes
15 up votes
2 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)

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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

Modulation of cardiac contraction and relaxation in heart failure: role of systemic inflammation

Is cardiac contraction and relaxation in heart failure modulated by the systemic inflammatory response?

There is overwhelming evidence that inflammatory biomarkers predict worse outcome in acute and chronic heart failure.

Despite the wealth of evidence, clinical trials in this area have either not been completed, failed, or provided inconclusive results.

The questions that remain are:
1) Is inflammation a mechanism... 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

Addressing this question may fill a decades-old gap in our understanding of the role of inflammation in heart failure, and potentially lead to novel prognostic biomarkers and/or improved therapeutics.

Feasibility and challenges of addressing this CQ or CC

All the preclinical and clinical tools are available.

Name of idea submitter and other team members who worked on this idea Antonio Abbate

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8 net votes
14 up votes
6 down votes
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Goal 2: Reduce Human Disease

What is the role of chronic inflammation in lung complications in the HAART era?

With the advent of HAART HIV-infected subjects are living longer. Lung infectious complications so common in the early stages of the HIV epidemic have been replaced by those associated with chronic inflammation (COPD, pulmonary hypertension, lung cancer). Furthermore, this chronic inflammation is likely contributing to premature vascular complications (i.e coronary disease) seen in this population. All of these complications... 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

Addressing the role of chronic inflammation in chronic lung and vascular diseases will impact both the HIV population and our growing U.S. aging population. Approaches to the question could include:
1.. Causes of chronic inflammation
- Antiretroviral drugs, persistent HIV, persistence of other viruses, exogenous retroviral elements, exosomes, other epidemiologic exposures
2. Downstream mechanistic effects of chronic inflammation
- Alterations in gene regulation, alterations in oxidative stress, direct tissue damage
3. Clinical outcomes of chronic inflammation
- Lung – COPD, pulmonary HTN, cancer, interstitial lung disease, asthma.
- Vascular compartment - premature coronary and vascular disease
- Does HIV-infection itself require alterations in treatment modalities for lung disease
- Does HIV infection itself alter the outcome of chronic lung disease?
4. Therapeutic options
- Directed against the cause – i.e. antivirals.
- Immune specific targets against inflammatory mediators

Feasibility and challenges of addressing this CQ or CC

The critical challenge for this question lies in the fact that complications caused by chronic inflammation such as COPD and coronary disease will by definition take years to develop. Intervention trials will take even longer. This is not like the early HIV epidemic, where complications were primarily infectious and could be seen and addressed quickly. Because of this chronic nature, it will necessary to try and establish cohorts with long term follow-up. Furthermore, it will be critical to have well defined appropriate HIV-uninfected cohorts to compare the HIV-infected population to.

Name of idea submitter and other team members who worked on this idea Homer L. Twigg III on behalf of the INHALD Consortium

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1 net vote
19 up votes
18 down votes
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Goal 2: Reduce Human Disease

Inflammation and outcomes following pediatric cardiac operations

What is the contribution of the inflammatory response to postoperative recovery following pediatric cardiac operations and what strategies can improve outcomes?

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

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Congenital heart disease is the most common cause of birth defects, with about 40,000 new cases born per year in the US. Affected individuals experience morbidity and mortality that generate health and economic consequences significantly out of proportion to their numbers. An estimated 10,000 of these patients will undergo cardiac surgery involving cardiopulmonary bypass (CPB). Furthermore, it is estimated that over 300,000 children in the US under age 21 have congenital cardiovascular disease and that 38% of these children will have had one or more surgical procedures. The use of CPB in neonates in particular has increased steadily over the past two decades. Further, neonates are generally sicker and consume more resources, including postoperative mechanical ventilation, ICU stay and hospital stay. Consequently, reducing the deleterious effects of CPB will have the largest impact in this group of patients.

Feasibility and challenges of addressing this CQ or CC

Research has begun to assess the inflammatory response to cardiopulmonary bypass in pediatrics. However, the magnitude and importance of its contribution to complicating postoperative recovery remains elusive. Clinical trials have begun to assess the efficacy of generalized anti-inflammatory therapies, typically steroids, with conflicting results. No therapy has been recognized as the standard of care. It’s critical that we improve our understanding of the molecular and cellular mechanisms of this inflammatory response and resulting derangements in vascular permeability and develop novel treatment strategies for infants and children undergoing cardiopulmonary bypass.

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1 net vote
16 up votes
15 down votes
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Goal 2: Reduce Human Disease

Targeting Inflammation in Venous Thromboembolism

What is the role of inflamation in venous thromboembolism, both DVT and PE. If the inflammatory response can be controlled, then clot formation should be able to be decreased or eliminated without bleeding potential. The effect of the inflammatory response on the wall of the veins, both in the legs and the lungs, leads to changes that result in pain and swelling (legs) and pulmonary artery hypertension (lungs). Inhibiting... more »

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

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I would suggest that studies addressing this issue using new targeted anti-inflammatory medications be supported in both large animal models (close to human) and in clinical translational studies.

Feasibility and challenges of addressing this CQ or CC

This is feasible and doable - there is data suggesting that inflamatory inhibition with agents that target the selectins (for example) lead to a lessening of thrombosis, and decreases in vein wall damage, all without bleeding potential. These conepts in animals need to be evaluated in clinical studies. Additionally, there are other off-shoots such as studies with biomarkers of inflammation and how they can be helpful in making the diagnosis and predicting the response to therapies.

Name of idea submitter and other team members who worked on this idea Thomas Wakefield

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2 net votes
2 up votes
0 down votes
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Goal 2: Reduce Human Disease

Clinical Trials in Pediatric Sleep Disorders

Effect of anti-inflammatory medications (including nasal steroids and leukotriene antagonists) in children with obstructive sleep apnea syndrome, stratified for severity of OSAS as well as presence of atopy.

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

Details on the impact of addressing this CQ or CC

Small studies suggest a therapeutic effect of anti-inflammatory medication in childhood OSAS. This may be especially useful in children with residual OSAS following adenotonsillectomy (as CPAP adherence tends to be low) or children who are poor candidates for surgery. Current studies have been limited to children with extremely mild OSAS, have not determined whether atopy plays a role in the response to therapy, and have been limited to very short-term trials.

Name of idea submitter and other team members who worked on this idea ATS Member

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1 net vote
1 up votes
0 down votes
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Goal 2: Reduce Human Disease

Can transcutaneous carboxyhemoglobin measure endogenous heme oxygenase activity?

Non-invasive measurement of transcutaneous carboxyhemoglobin (SpCO) by CO-oximetry has been shown to reflect disease activity in asthma, allergic rhinitis, Staphylococcal pneumonia/sepsis and to correlate positively with lung function in cystic fibrosis. Given published studies of heme oxygenase activity in these diseases as a reflection of oxidant or inflammatory activity, does measurement of SpCO reflect endogenous... more »

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

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Laboratory measurement of heme oxygenase activity in inflammatory and states of oxidative activity in multiple disease states, lung diseases for instance, has become important in measuring disease severity and activity as well as being an indicator of disease modification by gene polymorphisms of heme oxygenase. The simple measurement of transcutaneous carboxyhemoglobin if correlated with heme oxygenase activity would provide a ready assessment for clinicians in the clinical setting.

Feasibility and challenges of addressing this CQ or CC

In a setting in which heme oxygenase activity is measured and clinical patients of varying diseases are available, this question could be answered reasonably easily without technical difficulty.

Name of idea submitter and other team members who worked on this idea Lawrence E. Kurlandsky, MD

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-24 net votes
1 up votes
25 down votes
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Goal 2: Reduce Human Disease

What are the Determinants of Short Term Prediction of Heart Attacks?

In spite of many years of research, we still cannot predict the short term risk of a heart attack or sudden CHD death. Most CHD deaths occur outside of the hospital. In spite of improvement of out-of-hospital emergency care, most “sudden death events” are still not successfully resuscitated.

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

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There is strong evidence of interrelationship between inflammation, thrombogenesis, especially activation of tissue factor and platelets, and risk of a heart attack or sudden death. This is especially true in individuals who have pneumonia, influenza, etc. but also perhaps in relationship to environmental factors such as air pollution. Development of early identification and treatment approaches could substantially reduce CHD mortality.

Feasibility and challenges of addressing this CQ or CC

The NHLBI has certainly had a major commitment in studying the interrelationship between inflammation and CHD. However, there is a need to go into the field and evaluation the interrelationship between inflammation, especially infection, drug therapies and short term acute precipitation of heart attacks. For example, there is suggestive evidence that older individuals on aspirin who have pneumonia may have reduced risk of a heart attack and sudden CHD death. Further studies linking work at the National Institute of Allergy and Infectious Diseases and the Heart and Lung Institute should attempt to further understand the interrelationships between infection, inflammation, and activation of tissue factor and platelets, and risk of thrombosis and heart attack and whether specific drug therapies, especially in high risk older individuals or even among individuals who have had previous CVD or high atherosclerotic burden, whether newer drugs could substantially reduce the risk of a heart attack.

Name of idea submitter and other team members who worked on this idea Lewis H. Kuller, MD, DrPH

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

Cellular senescence and age-related lung disease?

What is the role of cellular senescence in age-related lung disease? Do environmental factors, including smoking, contribute to the pathogenesis of lung disease through their ability to induce premature senescence? Does the accumulation of senescent cells in distal organs contribute to age-related lung disease through systemic inflammation?

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 Ferruccio Galbiati

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-6 net votes
4 up votes
10 down votes
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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?

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

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-4 net votes
1 up votes
5 down votes
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