Announcing the 2022 DIG Recipients

2022 DREAM Innovation Grant Recipients

Please join us in congratulating Duke Anesthesiology’s 2022 DREAM Innovation Grant (DIG) recipients, Lisa Einhorn, MD, and Shad Smith, PhD. They have each been awarded $30,000 in seed money for their innovative pilot studies, which ultimately helps them apply for and obtain extramural funding.

DIGs are part of the department’s Duke DREAM Campaign, established in 2007 to support research programs and initiatives. DIGs support innovative high-risk and potentially high-reward investigations to accelerate anesthesia and pain management. Funding provided by the DIGs will support each recipient for one year, during which pilot studies can be conducted.

Lisa Einhorn, MD

Lisa Einhorn, MD

“Pediatric Pain Optimization After Tonsillectomy: A Randomized Double Blind Methadone Pilot Study”

Dr. Einhorn’s DIG research aims to explore an innovative approach to managing pediatric perioperative pain with the use of intraoperative methadone and determining its optimal dose in children following tonsillectomy. The long-term goals are to improve pain control after a common pediatric procedure and reduce the need for outpatient opioid prescriptions, which often remain partially unused and undisposed.

Shad Smith, PhD

Shad Smith, PhD

“Mechanisms of Genetic Regulation of Nociception and Injury Resilience by Mras

Dr. Smith’s DIG research will investigate a gene recently discovered to protect against chronic pain, MRAS, by characterizing its function and interactions with nociceptive pathways, in order to better understand and utilize innate healing processes.

To date, $982,374 in DREAM Innovation Grants have led to nearly $15 million in extramural funding.

The annual DIG competition launched in 2010. We thank those who applied this year, and we express our sincere appreciation to the DIG Application Review Committee and the donors who continue to support our research programs and initiatives, ultimately helping us transform the future of patient care and protect quality of life for years to come.

We look forward to seeing Drs. Einhorn and Smith’s innovative projects develop.

Stacey HiltonAnnouncing the 2022 DIG Recipients
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Dr. Meng Named FAER Grant Recipient

Marie-Louise Meng, MDThe Foundation for Anesthesia Education and Research (FAER) has awarded Duke Anesthesiology’s Marie-Louise Meng, MD, a two-year, $250,000 Mentored Research Training Grant for her project, “Cardiovascular Risk Prediction for Improved Maternal Health,” which aims to create a risk score to predict cardiovascular events after pregnancy complicated by preeclampsia.

Preeclampsia (PreX) is a common cause of maternal morbidity and mortality, complicating 2-12 percent of pregnancies. PreX is a risk factor for acute and chronic cardiovascular (CV) disease. Mortality due to PreX is largely preventable, but despite this, accounts for more than 62,000 deaths per year globally. While PreX is a strong independent risk factor for postpartum CV events, there remains a challenge in identifying women with PreX who are at greatest risk for acute CV events, likely contributing to failure in preventing these complications.

Improved modeling may identify PreX patients at risk for CV events who would benefit from treatment for prevention of CV events. Using administrative data, an obstetric comorbidity index was developed to predict all forms of morbidity at delivery, however, this index is not PreX nor CV morbidity specific. Improved models specific to PreX could change management of these patients by improving prompt access to appropriate care.

The long-term goal of Meng’s research is to reduce CV morbidity due to PreX. The study’s objective is to create a comprehensive risk model to predict acute CV events in women with PreX. Meng’s central hypothesis is that a model inclusive of CV and PreX-specific factors will improve an existing obstetric comorbidity index. To test this hypothesis, she will leverage the Premier dataset and a combined Duke/University of North Carolina dataset to create and validate a CV event specific risk score in women with PreX using both traditional and machine learning methods; then, prospectively add measures of plasma biomarkers to improve model performance.

Meng’s research project mentors are Duke Anesthesiology’s Dr. Ashraf Habib (secondary), chief of the department’s Women’s Anesthesiology Division, and Duke Medicine’s Dr. Svati Shah (primary). “I am grateful for the opportunity to complete this project and for Dr. Shah’s devoted mentorship,” says Meng, assistant professor of anesthesiology.

Stacey HiltonDr. Meng Named FAER Grant Recipient
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Dr. Karhausen Awarded NIH Grant for Septic Shock Study

Jorn Karhausen, MDThe National Institutes of Health’s National Institute of General Medical Sciences has awarded Duke Anesthesiology’s Jorn Karhausen, MD, a four-year, $1,719,290 R01 grant for his project, “Platelet-Mast Cell Interactions as Determinants of the Vascular Pathology in Septic Shock.”

Development of shock in sepsis defines a dramatic deterioration of clinical status and is linked to a significant increase in morbidity and mortality rates. However, the cellular and molecular mechanisms determining the vascular pathology of septic shock remain undefined.

Karhausen’s previous work established mast cells (MC) as key effector cells of vascular pathology in different disease contexts. Because MC products are found in the plasma in shock, but not during sepsis alone, this supports that MC activation is a central event leading to septic shock.

Based on extensive preliminary work, they hypothesize that specific signaling interactions between platelets from within the blood stream and MCs, which are located close by, but outside of the blood vessels, drive the vascular pathology of septic shock. The objectives of this study are to 1) comprehensively define the mechanisms of MC-mediated vascular pathology in sepsis, 2) elucidate the specific mechanism by which platelets trigger MC responses and resultant vascular pathology and 3) better define the clinical sepsis phenotype using biomarkers of platelet-, vascular- and MC- activation in patients.

To provide first evidence how MCs shape key features of shock in sepsis, Karhausen and his co-investigators will employ state-of-the- art technologies ranging from dynamic photoacoustic imaging of the microvasculature to gene expression modeling from clinical samples. This comprehensive approach will be made possible through a strong collaborative team, including groups from the School of Engineering, the Center for Applied Genomics and Precision Medicine and the Department of Pathology at Duke, as well as the Department of Cell Biology and Physiology at UNC.

“Together, this project constitutes a key step towards our long-term goal to establish MC responses as a biomarker of sepsis biology,” says Karhausen, associate professor of anesthesiology, “and to develop novel therapeutic strategies that may directly target the mechanisms of disease progression in sepsis.”

Stacey HiltonDr. Karhausen Awarded NIH Grant for Septic Shock Study
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Dr. Bauer Awarded NIH Grant for Maternal Sepsis Study

Melissa E. Bauer, DO

Melissa E. Bauer, DO

The National Institutes of Health’s Eunice Kennedy Shriver National Institute of Child Health & Human Development has awarded Duke Anesthesiology’s Melissa Bauer, DO, a two-year, $1,575,463 UG3 grant for her project titled, “Large-Scale Implementation of Community Co-led Maternal Sepsis Care Practices to Reduce Morbidity and Mortality from Maternal Infection.” This award is part of a phased five-year grant.

Maternal infection progressing to sepsis is the leading cause of direct maternal mortality in the United States with high preventability. Nationally, there has been no improvement in the overall percentage of deaths from infection since 1987 when the Centers for Disease Control and Prevention began maternal mortality surveillance, despite improvements in overall sepsis care for non-pregnant patients.

Dr. Elliott Main

Elliott Main, MD

Bauer’s research with multi-PI, Dr. Elliott Main of Stanford, focuses on a community co-led strategy to refine, test and disseminate universal pregnancy-adjusted screening, diagnostic criteria and treatment practices for sepsis to overall reduce maternal morbidity and mortality from maternal infection. The overall objectives of the research are to 1) identify patient-based and clinician-based barriers, 2) refine sepsis screening in pregnancy and 3) implement a large-scale quality improvement collaborative.

Bauer and Main will pursue the following aims: 1) develop and support a maternal sepsis community leadership group of community representatives, patients, patient advocates, survivors, and family members of those who did not survive to inform and engage substantively throughout the study; 2A) identify patient-based barriers to care for severe maternal infection and sepsis; 2B) identify clinician-based barriers to implementation; 2C) design strategies to implement evidence-based sepsis care interventions, specifically targeted to address and overcome barriers identified in aims 2A and 2B; 3) establish test characteristics of a pregnancy-adjusted intrapartum sepsis screen.

“Our research is innovative because it is one of the first studies to co-lead a large-scale maternal initiative with representatives from the community, patient advocate representatives, and patients and families with lived experience with sepsis,” says Bauer, associate professor of anesthesiology. “We expect that by identifying and addressing barriers to care and implementation through community, clinician, and patient partnerships, this large-scale implementation initiative will serve as a national model to reduce maternal mortality and morbidity from sepsis, reduce disparities, and potentially serve as a model to address other causes of mortality.”

Stacey HiltonDr. Bauer Awarded NIH Grant for Maternal Sepsis Study
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Dr. Privratsky Awarded NIH Grant to Develop Novel Therapeutic

Jamie Privratsky, MD, PhDThe National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Diseases has awarded Duke Anesthesiology’s Jamie Privratsky, MD, PhD, a five-year, $1,610,000 R01 grant for his project titled, “Novel Mitochondrial Protective Properties of Annexin A1.”

Acute kidney injury (AKI) is one of the most common forms of perioperative organ injury occurring in up to 30 percent of post-surgical patients, and it significantly increases morbidity and mortality. A number of vascular and transplant surgeries require interruption of blood flow to the kidney, rendering the kidney ischemic and causing significant metabolic stress. The timing of this kidney insult is known; thus, the possibility exists to intervene to protect the kidney. However, no treatment options exist to prevent or treat post-surgical AKI.

Privratsky’s research seeks to understand the cellular mechanism of a novel kidney protective therapeutic that could be given prior to surgery or kidney transplantation to protect the kidney from injury. The development of kidney protective therapeutics has the potential to greatly improve outcomes in the millions of people who undergo surgical operations and kidney transplants each year.

Privratsky and his co-investigators have characterized a novel peptide mimetic of the endogenous pro-resolving molecule annexin A1 that in their recently published data shows that it can ameliorate ischemic kidney injury in mice by augmenting mitochondrial function and limiting kidney tubular cell death. Despite the promise of their therapeutic to limit kidney injury, the novel mechanism by which it protects the kidney is not known. Thus, the objectives of his proposal are to determine the cellular receptor and signaling mechanism through which their therapeutic augments mitochondrial function and metabolism to limit AKI.

“Upon the completion of the study, we will be primed to pursue translational studies and further drug development,” says Privratsky, assistant professor of anesthesiology. “The development of our new therapeutic would not only help limit postoperative and transplant AKI but also have broad implications for protection of other organs following surgery and transplantation.”

Stacey HiltonDr. Privratsky Awarded NIH Grant to Develop Novel Therapeutic
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Dr. Wischmeyer Awarded Grant for COVID-19 Rehabilitation Study

Paul E. Wischmeyer, MD, EDICThe National Institutes of Health’s Eunice Kennedy Shriver National Institute of Child Health and Human Development has awarded Duke Anesthesiology’s Paul Wischmeyer, MD, EDIC, FASPEN, FCCM, a five-year, $4,059,863 R01 grant for his project titled, “Remotely Monitored, Mobile Health-Supported High Intensity Interval Training After COVID-19 Critical Illness (REMM HIIT-Covid19).”

This trial utilizes high-level exercise testing, like that used by Olympic athletes, at hospital discharge in COVID-19 ICU survivors to personalize and target home exercise goals to promote recovery of physical function, exercise tolerance and quality of life. This program is unique and innovative as it allows personalized high intensity training exercise to be performed in patients at home while they are monitored remotely by physical therapists via IWatch and IPhone mobile device technology. This allows coaching and adaptation of exercise performance directly by physical therapists on a daily basis. The trial will be conducted at four leading US Academic ICU centers including Duke, Vanderbilt (co-site PIs: Drs. Wes Ely and Matthew Mart), University of Kentucky (site-PI: Dr. Peter Morris), and Ohio State University (site PI: Dr. Nathan Brummel).

This trial is critically and urgently needed as severe disease from COVID-19 continues to require hospitalization in 20 percent of adults, with a third of those patients requiring intensive care unit (ICU) treatment. While a growing number of patients are surviving COVID-19 critical illness, like other ICU survivors, the majority will experience significant post-hospital disabilities in physical function and exercise capacity, new-onset disability, muscle wasting/weakness, and new cognitive deficits. These difficulties, which can persist for months to years post-ICU, are collectively known as post-intensive care syndrome (PICS) and may be more severe in COVID-19 survivors.

The National Center for Medical Rehabilitation Research has deemed “research to address the rehabilitation needs of severe COVID-19 survivors…via new clinical trials of home-based rehabilitation interventions…with emphasis on use of mobile or digital devices” a priority area of research. In alignment with those priorities and the urgent public health need created by COVID-19 to overcome challenges to traditional rehabilitation strategies, Wischmeyer and co-PI Dr. Amy Pastva (PhD physical therapist) of Duke Orthopaedic Surgery will assess a successfully piloted novel home rehabilitation program to improve recovery of cardiorespiratory fitness (CRF) and physical function in COVID-19 ICU survivors – specifically, survivors who frequently experience PICS.

The unique strengths of this randomized trial include a home-based innovative, tailored, structured, and progressive multidomain rehabilitation strategy, scientifically rigorous clinical trial design, an inter-disciplinary research team, access to a large COVID-19 ICU patient pool, innovative mobile health device platform, statistical power, patient safety, and inclusion of CRF performance-based, as well as patient-reported post-hospital outcomes. The key to the approach of this trial is Wischmeyer and Pastva’s mHealth platform, in which patients are given Apple watches and iPhones preloaded with their software allowing them to remotely download data after each exercise session to provide personalized up-coaching via videoconferencing in a home setting. This novel home exercise concept has been successfully piloted at Duke in cancer patients preparing for bone marrow transplant by Dr. Tony Sung and his team; Sung will serve as key co-investigator on this new RO1 with Wischmeyer.

Previous studies of home-based physical rehabilitation in ICU survivors have utilized unsupervised exercise training without a personalized exercise prescription, and none have done so while actively monitoring and targeting exercise via physiologic data such as heart rate or included strength and balance training. To address this gap in knowledge, the investigators will randomize 140 COVID-19 ICU survivors being discharged home to their study to test the hypothesis that the REMM-HIIT exercise intervention, in contrast to exercise education alone, will improve CRF and muscle strength/mass and improve physical function and quality of life.

Wischmeyer says, “We hope this study of post-ICU personalized high-intensity interval exercise training will lead to more ICU survivors from COVID-19 and other ICU illness who are able to return to active, productive lives versus ‘ICU victims’ who often suffer long term disabilities that can persist for years after an ICU admission.”

Stacey HiltonDr. Wischmeyer Awarded Grant for COVID-19 Rehabilitation Study
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