Dr. Privratsky Receives Mentored Research Award

Jamie Privratsky, MD, PhDThe International Anesthesia Research Society (IARS) has awarded Duke Anesthesiology’s Jamie Privratsky, MD, PhD, a two-year, $175,000 2017 Mentored Research Award for his project, titled “The role of macrophage IL-1 signaling in acute kidney injury and recovery.”

According to the project statement, acute kidney injury (AKI) dramatically increases morbidity and mortality and can lead to downstream chronic kidney disease (CKD). The mechanisms that direct renal recovery after AKI and prevent the AKI to CKD transition are poorly understood.

Based on preliminary data, Dr. Privratsky’s central hypothesis is that IL-1R1 activation sustains detrimental macrophage polarization to drive acute renal injury and promote the AKI to CKD transition, culminating in kidney fibrosis. The specific aims of he and his team of investigators include: Aim 1) determine the effects of IL-1R1 signaling on renal macrophage polarization during AKI. Mice with macrophage-specific deletion of IL-1R1 (IL-1R1 MKO) and controls will be subjected to ischemia/reperfusion (I/R)-induced AKI. They will measure the severity of kidney damage, assess the polarization of infiltrating macrophages via fluorescent cell sorting and RT-PCR, and characterize injury in renal tubular cells following co-culture with isolated WT and IL-1R1 MKO macrophages from injured kidneys. Aim 2) determine the effect of IL-1R1 receptor signaling on the development of renal fibrosis following AKI. Investigators will subject IL-1R1 MKO mice and littermate controls (WT) to I/R-induced AKI and 28 days later examine the extent of kidney fibrosis. At multiple time points, intra-renal macrophages will be phenotyped by fluorescent cell sorting and analyzed for pro-inflammatory and pro-fibrotic gene expression by RNAseq. The capacity of a commercially available IL-1R1 antagonist to alter macrophage polarization and prevent renal fibrosis following AKI will be tested.

According to Dr. Privratsky, an assistant professor of anesthesiology in Duke Anesthesiology’s Critical Care Medicine Division, these studies should underpin the development of novel immunomodulatory therapies for AKI, which are expected to have a significant positive impact on perioperative and critically ill patients.

Chris KeithDr. Privratsky Receives Mentored Research Award
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Dr. Berger Receives Prestigious K76 Award

Miles Berger, MD, PhDThe National Institutes of Health has awarded Duke Anesthesiology’s Miles Berger, MD, PhD, and his team of investigators a Paul B. Beeson Emerging Leaders Career Development Award in Aging (K76); a five-year, $1,195,505 grant for their project, titled “Neuro-inflammation in Postoperative Cognitive Dysfunction: CSF and fMRI Studies.”

According to the project description, each year, more than 16 million older Americans undergo anesthesia and surgery, and up to 40 percent of these patients develop postoperative cognitive dysfunction (POCD), a syndrome of postoperative thinking and memory deficits. Although distinct from delirium, POCD (like delirium) is associated with decreased quality of life, long term cognitive decline, early retirement, increased mortality, and a possible increased risk for developing dementia, such as Alzheimer’s disease. Strategies are needed to prevent POCD, but first, we need to understand what causes it. A dominant theory holds that brain inflammation causes POCD, but little work has directly tested this theory in humans. Dr. Berger and his team’s preliminary data strongly suggests that there is significant postoperative neuro-inflammation in older adults who develop POCD.

In this K76 award, the team of investigators will prospectively obtain pre and postoperative cognitive testing, fMRI imaging and CSF samples in 200 surgical patients over the age of 65. This will allow them to evaluate the role of specific neuro-inflammatory processes in POCD, its underlying brain connectivity changes, and postoperative changes in cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarkers, such as the microtubule-associated protein tau. This project will advance understanding of neuro-inflammatory processes in POCD and clarify the potential link(s) between these processes and postoperative changes in AD pathology, in line with the National Institute of Aging’s mission to understand aging and fight cognitive decline due to AD.

The K76 is a mentored career development award; Dr. Berger’s mentoring team includes Drs. Joseph Mathew (chairman of Duke Anesthesiology) and Harvey Cohen (director of the Duke Center for the Study of Aging and Human Development ), as well as Drs. Roberto Cabeza (from the Duke Center for Cognitive Neuroscience), Kent Weinhold (vice chair for research of Duke Surgery), and Heather Whitson (deputy director of the Duke Center for the Study of Aging and Human Development). Co-investigators and collaborators include Drs. Niccolò Terrando (Duke Anesthesiology), Jeffrey Browndyke (Duke Psychiatry & Behavioral Sciences) and David Murdoch (Duke Medicine).

During this K76 grant period, Dr. Berger, an assistant professor of anesthesiology, will also complete an individually-tailored MS degree in translational research that will include training in immunology methods, fMRI imaging, cognitive neuroscience, geroscience, and physician leadership. This career development plan will provide him with transdisciplinary skills to pursue his longer term goal of improving postoperative cognitive function for the more than 16 million older Americans who have anesthesia and surgery each year.

Chris KeithDr. Berger Receives Prestigious K76 Award
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Neuroscientists Awarded School of Medicine Voucher

The Duke University School of Medicine has awarded an $8,000 voucher to Duke Anesthesiology’s Niccolò Terrando, PhD, and Zhiquan Zhang, PhD, for their project, titled “Preventing Memory Dysfunction after Surgery with a Novel Pro-Resolving Peptide from Annexin-A1.”

Major surgery, including cardiac and orthopedic, often causes neurological complications such as delirium and postoperative cognitive dysfunction. According to the project investigators, there are currently no safe and effective therapies to prevent or limit these complications in patients. Dr. Zhang previously developed a bioactive peptide (ANXA1sp) derived from the N-terminal domain of the human protein Annexin-A1 (ANXA1), a critical molecule involved in the resolution of inflammation. Ongoing studies with this peptide are revealing promising effects in protecting the brain against excessive neuroinflammation after surgery, which is becoming a key contributor to memory deficit.

This voucher, in collaboration with the Mouse Behavioral and Neuroendocrine Shared Core, will help Drs. Zhang and Terrando validate the effects of this peptide on cognitive, as well as higher order memory tasks, in their models of cognitive dysfunction after major surgery. Given the impact of neuroinflammation on memory function across many different neurological disorders, this therapy could provide fundamental knowledge to direct future studies and therapy development for numerous conditions such as Alzheimer’s disease and other dementias.

Dr. Terrando is an assistant professor in anesthesiology, a collaborator with Duke Anesthesiology’s Center for Translational Pain Medicine and the director of the Neuroinflammation and Cognitive Outcomes Laboratory which studies the mechanisms underlying postoperative neurocognitive disorders with a strong focus on neuroinflammation, innate immunity and behavior. Dr. Zhang is an assistant professor in anesthesiology and a member of Dr. Terrando’s lab.

Chris KeithNeuroscientists Awarded School of Medicine Voucher
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Dr. Kwatra Awarded Funding for Glioblastoma Study

Madan M. Kwatra, PhDGenzada Pharmaceuticals has awarded Dr. Madan Kwatra a two-year, $763,200 grant, titled “Evaluation of novel anti-cancer agents, either alone or in combination, for activity against glioblastoma subtypes: a personalized medicine approach.”

Genzada specializes in pharmaceuticals derived from plants. Their lead compounds have shown activity in preclinical models of several cancers. These agents will be tested against glioblastoma because they have the ability to penetrate the blood brain barrier and represent a natural, alternative therapy against glioblastoma. The compounds will be tested against GBMs of multiple molecular subtypes allowing for a personalized and targeted approach to treating this deadly disease.

Dr. Kwatra is an associate professor in anesthesiology and the director of the Molecular Pharmacology Laboratory at Duke Anesthesiology, which focuses on understanding the role of G protein-coupled receptors in human diseases.

Chris KeithDr. Kwatra Awarded Funding for Glioblastoma Study
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FAER Awards Dr. Quinones Research Training Grant

Quintin Quinones, MD, PhDThe Foundation for Anesthesia Education and Research has awarded Duke Anesthesiology’s Quintin Quinones, MD, PhD, a two-year, $175,000 mentored research training grant, titled “Reversible Immunomodulation as a Strategy for Ischemia Tolerance in Hibernation.” His mentor for this grant is Dr. Mihai Podgoreanu, chief of the Cardiothoracic Anesthesia Division.

During surgery or critical illness, patients sometimes suffer organ dysfunction related to uncontrolled inflammation. There are currently no drugs that effectively treat this problem. To work towards new treatments, Dr. Quinones and a team of investigators have developed a surgical model to study a hibernating mammal known as the arctic ground squirrel (AGS). These animals show a remarkable, natural resistance to injury in a robust surgical model that closely mirrors what humans experience during major heart surgery. To understand how arctic ground squirrels are different, they’re comparing them to rats in the same surgical model; rats do not show any natural resistance and suffer organ dysfunction much in the way that humans do.

The focus of the study is a unique trait found in hibernators – the AGS can regulate its innate immune system to decrease inflammation following surgical injury. Dr. Quinones and his co-investigators will examine protein levels and the function of white blood cells in the AGS vs. the rat. They will also look at protein levels in human white blood cells. By understanding how the AGS is able to regulate its innate immune system, they hope to identify potential targets that will lead to treatments for human patients during surgery and critical illness.

There is a fundamental knowledge gap regarding the role of innate immunity in injury during ischemia and reperfusion in the perioperative period and during critical illness. Hibernating mammals enjoy natural resistance to ischemia/reperfusion injury as a result of adaptations that allow them to survive winter torpor-arousal cycles without injury. One such adaptation is natural reversible modulation of innate immunity that reduces responses to danger-associated molecular patterns and pathogen-associated molecular patterns. A comparative biology approach provides the opportunity to study animals that are naturally adapted to survive ischemia and reperfusion. Dr. Quinones hypothesizes that hibernator resistance to ischemia/reperfusion is secondary to reversible modulation of innate immunity.

Dr. Quinones is an assistant professor of anesthesiology in the department’s Cardiothoracic Anesthesia Division. His research on hibernation biology has been featured in several publications, including the journal, Anesthesiology (June 2016), as well as the 2016 edition and 2013 edition of Duke Anesthesiology’s annual BluePrint magazine.

Chris KeithFAER Awards Dr. Quinones Research Training Grant
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Simulation Specialist Receives Patient Safety Grant

Jeffrey M. Taekman, MDDurham Casualty has awarded Duke Anesthesiology’s Dr. Jeffrey Taekman $108,668 in funding for a patient safety project titled, “Simulation-Based Crisis Resource Management as a Risk Reduction Strategy for the Health System.”

Throughout medicine, safe and effective delivery of health care has relied on proper team coordination and communication. The Joint Commission cites failures of teamwork and communication as a root cause of more than 50 percent of sentinel events. These events can have both economic and patient safety implications. In perioperative medicine, communication breakdowns represent the second leading cause of preventable intraoperative error, resulting in patient harm, second only to technical error. Analysis of closed claims by the American Society of Anesthesiologists (ASA) and the American College of Surgeons (ACS) implicate poor communication as a major preventable cause of adverse events.

In order to combat communication errors, Dr. Taekman proposes to implement an interprofessional simulation-centric crisis resource management (CRM) learning experience within Duke University Hospital. The expected outcome of this project includes decreased malpractice liability exposure and improved patient outcomes.

The proposed program, with interprofessional simulation at its core, will be carried out in collaboration with the Department of OB/Gyn and the faculty and staff of the Duke Birthing Center. Dr. Taekman’s collaborators include Ankeet Udani, Zaneta Strouch, Chad Grotegut, Andrea Fiumefreddo, Joe Chapman, Trish Fletcher, and Jennifer Justice.  Dr. Taekman’s vision is to build a similar program for each of the high risk surgical/perioperative services.

Dr. Taekman is the assistant dean for educational technology and the director of the Duke Human Simulation and Patient Safety Center, a joint project of Duke Anesthesiology, the School of Medicine and the School of Nursing.

Chris KeithSimulation Specialist Receives Patient Safety Grant
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