CAPER Unit Awarded Grant to Study New Lipid Formulation

Duke Anesthesiology’s Critical Care and Perioperative Population Health Research (CAPER) Unit

Duke Anesthesiology’s Paul Wischmeyer, MD, EDIC and the Critical Care and Perioperative Population Health Research (CAPER) Unit have been awarded a $130,000 grant for their project, titled “Impact of SMOFlipid on Clinical Outcomes Among Patients Receiving Parenteral Nutrition: An Interrupted Time Series Analysis.” The researchers will use the funding to study the effect of a newly-implemented advanced parenteral nutrition lipid on clinical outcomes versus previously used Omega-6 soy lipid.

The grant was awarded by Fresenius-Kabi Inc. Wischmeyer serves as the principal investigator of the grant; co-investigators include Drs. Vijay Krishnamoorthy, Karthik Raghunathan, Tetsu Ohnuma, Krista Haines (Duke Surgery), and Surgical Intensive Care Unit fellow, Dr. Osamudiamen Obanor.

The research team will examine the hypothesized benefits of a new IV nutrition lipid used for total parenteral nutrition (TPN) on clinical outcomes in Duke’s patients since Duke adopted the new lipid in 2017. Duke was among the first academic health centers in the nation to widely adopt the new lipid as it was only FDA approved in 2017. Wischmeyer notes that parenteral nutrition has been traditionally thought to potentially lead to increased infection risk. However, he says recent large randomized trials in Intensive Care Unit (ICU) patients in high-impact journals (New England Journal of Medicine, Lancet, JAMA) have shown there is no longer any association of TPN with infectious risk, even in ICU patients; but it is unclear what factors have reduced this risk.

One hypothesis the newly-funded study will explore is that newer lipid formulations containing fish oil, olive oil and a “healthier” fat mix reduces infection versus previously utilized Omega-6 lipids that have been used in the US for more than 40 years. This new trial will look at all Duke patients from neonates to adults who received new, healthier (SMOF) lipid formulation at Duke. And, using the unique talents of the CAPER Unit, they’ll compare similar patients from the period immediately prior to the new lipids introduction looking for differences in infection, length of stay, liver injury, and other clinical outcomes.

Results of this study are expected to provide unique insight to specific contribution of new, healthier lipid formulations to TPN safety and improved clinical outcomes. This could also lead to larger clinical trials or large health outcome database research funding opportunities to explore this question and other methods to improve outcomes with TPN.

“The US has a unique opportunity to finally utilize a safe and more optimally-balanced lipid formulation that has shown preliminary data to reduce infection, length of stay and improve clinical outcomes,” says Wischmeyer, professor of anesthesiology and associate vice chair for clinical research. “This study with our Duke Anesthesiology CAPER Unit provides a unique ‘real-world’ clinical care research opportunity to evaluate the contribution of this long-awaited new generation of lipid formulations to improve outcomes.”

Stacey HiltonCAPER Unit Awarded Grant to Study New Lipid Formulation
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Dr. Martucci Earns Research Incubator Award

Katherine Martucci, PhDDuke Anesthesiology’s Katherine Martucci, PhD, is among the investigators on a cross-departmental research team that has been awarded a 2020 Research Incubator Award ($75,000 grant) from the Duke Institute for Brain Sciences (DIBS) for their project titled, “Neural Mechanisms Underlying Tobacco Withdrawal-Induced Hyperalgesia.”

This award is designed to promote high-risk/high-return neuroscience research that is collaborative, crosses disciplinary boundaries, and is likely to draw external funding. The collaborative project brings together Martucci, and Duke Psychiatry & Behavioral Sciences’ Drs. Maggie Sweitzer, F. Joseph McClernon and Alison Adcock.

Chronic pain and cigarette smoking influence one another, in that smokers are more likely to have pain, and individuals with pain are more likely to smoke. People with chronic pain have more difficulty quitting smoking, in part, because temporarily going without smoking (early withdrawal) leads to increased pain sensitivity.

The goal of the study is to examine the brain’s response to heat pain stimuli among smokers in early withdrawal, to better understand the reasons for increased pain sensitivity. Daily smokers will complete two fMRI sessions, one after smoking as usual, and one after not smoking for 24 hours. During the scans, participants will experience heat pain delivered through an electrode and will provide ratings of their pain response. It is expected that participants’ ratings of pain in response to heat stimuli will be greater during the withdrawal session, and that this increased pain will be associated with greater activation throughout a network of brain regions involved in perceiving pain. This approach will allow the research team to determine which brain regions are most involved in pain sensitivity during withdrawal and which will help to identify targets for treatment. In addition, these processes might differ among smokers who also have chronic pain, compared to those who do not. As such, half of the participants will be those diagnosed with chronic pain, while the other half will be pain-free. The investigators anticipate that the effects of smoking withdrawal on pain-related brain function will be more pronounced among those with chronic pain.

Stacey HiltonDr. Martucci Earns Research Incubator Award
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2021 DREAM Innovation Grant Recipients Revealed

2021 DREAM Innovation Grant Recipients

Congratulations to three Duke Anesthesiology faculty, Drs. Michael Devinney, Heath Gasier and Marie-Louise Meng, on being selected as the 2021 DREAM Innovation Grant (DIG) recipients. The much-anticipated announcement was made on October 28, 2020 at Dr. Joseph Mathew’s virtual Chair’s Rounds.

Congratulations to the 2021 DIG winners:

Michael Devinney, MD, PhD

“Proteomic Determination of Neuroinflammation in Postoperative Delirium”

Heath Gasier, PhD

“Heme Oxygenase-1 Regulation of Skeletal Muscle Inflammation and Mitochondrial Fitness in Sarcopenic Obesity”

Marie-Louise Meng, MD

“Myocardial Dysfunction and Cardiac Metabolism in Preeclampsia”

DIGs support innovative high-risk and potentially high-reward investigations to accelerate anesthesia and pain management research. Each year, an annual competition is held among junior to mid-career faculty members within Duke Anesthesiology, who do not have established NIH funding. They compete for a DIG by submitting their most innovative research ideas to the DIG Application Review Committee, which was led by the late Dr. William Maixner, who was dedicated to transforming the future of patient care through innovative research.

Each DIG recipient can receive up to $30,000 in seed money, which supports their innovative pilot study for one year and ultimately helps them apply for and obtain extramural funding. One of the grants is reserved to support a beginning scientist (within five years of completion of residency or fellowship). The other award(s) are used as a seed grant to help investigators obtain preliminary data to support a new application to the National Institutes of Health. These grants are funded through a combination of private donors, private companies, alumni, and faculty. To date, $922,374 in DREAM Innovation Grants have led to nearly $15 million in extramural funding. Click here to view the previous DIG recipients and learn more about their projects.

DIGs are part of the department’s Duke DREAM Campaign, which launched in 2007 to support Duke Anesthesiology’s research programs and initiatives. These grants create an avenue for healthy competition among faculty, inspire ingenuity, promote the careers of young physician investigators, enhance donor communication, and further the department’s academic mission. DIGs help to bridge the gap between training and progression to independent investigator status.

Stacey Hilton2021 DREAM Innovation Grant Recipients Revealed
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Dr. Ghadimi Earns Mentored Research Award

Kamrouz Ghadimi, MDDuke Anesthesiology’s Kamrouz Ghadimi, MD, has been awarded the 2020 International Anesthesia Research Society (IARS) Mentored Research Award ($175,000, two-year grant) to study “Right Ventricular Metabolic Dysregulation after Surgery for Heart Failure.”

Perioperative right heart failure (RHF) is the leading cause of death within 30 days of left ventricular assist device and heart transplant operations. The objective of Ghadimi’s research is to identify cardiometabolic pathways that underlie early RHF after these operations due to changes in right ventricular (RV) afterload and heterogeneity in response to inhaled pulmonary vasodilators (iPVD). Supported by preliminary metabolomic analyses, the central hypothesis posits that RV-pulmonary arterial (PA) coupling is optimized in the responder phenotype, which signals efficient fatty acid oxidation in RV myocardium. Study aims include 1) quantifying differences in key metabolites using targeted mass spectrometry in serial plasma and RV myocardial samples to determine cardiometabolic pathways, including dysregulated fatty acid oxidation, that underlie early RHF and heterogeneity in response to iPVD, and 2) identifying baseline biomarkers reflecting fatty acid oxidation defects that are associated with RV-PA coupling status, iPVD response phenotypes, and early RHF development to create an integrated clinical-molecular model for outcome prediction in critically-ill patients.

The foundation for this mentored research training grant is embedded in the INSPIRE-FLO clinical trial that Ghadimi has led since 2017 and the biospecimen repository that derived from trial patients undergoing advanced heart failure surgery, such as left ventricular assist device insertion and heart transplantation. As part of this award, Ghadimi and his research team plan to enroll patients undergoing routine cardiac operations by utilizing the vast resources available through Duke Anesthesiology’s Clinical Research Unit. As a member of the Shah laboratory at the Duke Molecular Physiology Institute, Ghadimi is being mentored by laboratory principal investigator (PI) and associate dean of genomics, Dr. Svati Shah, to accomplish the aims of this investigation and to acquire the necessary experiential training to become an independent clinical and translational investigator. As a previous recipient of the NIH T32 award (sponsored by the National Institutes of General Medical Sciences, PI: David Warner, MD), Ghadimi will obtain a Master in Health Science (MHSc) from the NIH-Duke Clinical Research Training Program and pursue additional coursework in precision medicine during this award.

“Receiving this grant is the next step in achieving my long-term goal of using translational methods to identify molecular pathways of right heart failure that will lead to potential novel therapeutic strategies and biomarker discovery for personalized patient care,” says Ghadimi, associate professor of anesthesiology and critical care. “With a large sense of gratitude, being named an award recipient has helped validate (1) the countless hours of hard work and sacrifice that were required to mature this project with my group of mentors and advisors, (2) the time my research team and I have utilized to coordinate multiple resources at Duke that are essential for proper acquisition and storage of biospecimens associated with our parent clinical trial, INSPIRE-FLO, and (3) the importance of ongoing professional development through enrollment in formal research training.”

Stacey HiltonDr. Ghadimi Earns Mentored Research Award
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Dr. Terrando Awarded Grant for COVID-19 Related Research

Niccolò Terrando, BSc (hons), DIC, PhDThe National Institutes of Health has awarded Duke Anesthesiology’s Niccolò Terrando, BSc, DIC, PhD, a one-year, $322,620 supplement grant to his R01-funded project, titled “Delirium Superimposed on Dementia Intersects with COVID-19.”

Delirium has become a common complication of COVID-19 that further impairs the recovery of already debilitated patients, in particular older adults. Terrando and his co-investigators are studying the role of neuroinflammation as a putative driver of delirium pathogenesis. For this supplement, they will explore how lung injury, akin to COVID-19 infection, leads to delirium by impairing the blood-brain barrier and triggering immune cell trafficking into the brain.

Terrando aims to develop a model of COVID-19 lung injury that activates the immune system to damage the brain, affecting areas that serve attention, memory, and thinking, and reverse these changes with an experimental drug in development. Findings from this research supplement will address this serious public health concern by providing fundamental knowledge on the pathogenesis of delirium following COVID-19-like infection. Such work has the potential to reduce the health care burden of COVID-19 associated with delirium and related neurologic complications, such as Alzheimer’s disease and related dementias (ADRDs).

“We are thrilled to develop this project in collaboration with Dr. Purushothama Rao Tata in the Duke Department of Cell Biology, an expert in murine lung injury models, and Dr. Harris A. Gelbard in the Center for Neurotherapeutics Discovery at the University of Rochester Medical Center that developed new therapeutics effective in resolving neuroinflammation, which we are currently testing in the R01 funded project,” says Terrando, associate professor in anesthesiology. “We are grateful for the National Institute on Aging’s continuous support, and we are looking forward to providing timely results that may curtail pathologic hallmarks of delirium and neurodegeneration resulting from COVID-19.”

Stacey HiltonDr. Terrando Awarded Grant for COVID-19 Related Research
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Dr. Devinney Receives Research Award

Michael Devinney, MDThe Society for Neuroscience in Anesthesiology and Critical Care (SNACC) has selected Duke Anesthesiology’s Michael Devinney, MD, PhD, as the 2020 recipient of its William L. Young Neuroscience Research Award for his project, titled “The Association of Blood-Brain Barrier Breakdown with Sleep Apnea and Postoperative Delirium.”

Using pre- and postoperative cerebrospinal fluid samples from the ongoing Sleep Apnea, Neuroinflammation, and cognitive Dysfunction Manifesting After Non-cardiac surgery (SANDMAN) study, Devinney and his co-investigators will determine whether blood-brain barrier breakdown occurs at higher levels in patients with sleep apnea, and whether increased postoperative blood-brain barrier breakdown is associated with worse postoperative delirium. As part of the SNACC award, Devinney will receive $5,000 to be applied toward research expenses for his winning project.

“I am honored to receive the 2020 William L. Young Neuroscience Research Award and grateful for the support from the Society for Neuroscience in Anesthesiology and Critical Care,” says Devinney, assistant professor of anesthesiology. “Also, I am very thankful for the excellent mentorship that I have received at Duke, the support of the Department of Anesthesiology, and the help we have received from our collaborators.”

Stacey HiltonDr. Devinney Receives Research Award
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