Division Chief Awarded Duke-Singapore Collaborative Grant

Ashraf S. Habib, MBBCh, MSc, MHSc, FRCADuke University and the Duke-National University of Singapore (NUS) Medical School have awarded Duke Anesthesiology’s Ashraf Habib, MBBCh, MSc, chief of the Women’s Anesthesia Division, and his collaborator at KK Hospital in Singapore, Ban Leong Sng, MD, a $200,000 grant for their Duke/Duke-NUS pilot project, titled “Evaluation and risk assessment for persistent postsurgical pain after breast surgery: a collaborative prospective cohort study.”

The overall aim of this study is to identify clinically-relevant and genetic risk factors for persistent postsurgical pain that can be reliably distinguished statistically. Specifically, the focuses include 1) risk factors representing biopsychosocial processes that influence chronic pain, such as pain and psychological vulnerability, and 2) genetic factors relating to mechanistic pathways to persistent pain generation.

According to the project’s abstract, breast cancer is a leading cancer diagnosis among women worldwide, with more than one million new cases each year. Chronic pain following breast cancer surgery has been recognized as a major humanitarian and socioeconomic burden, affecting more than 50 percent of patients after lumpectomy and mastectomy leading to chronic physical disability and psychological distress. This chronic pain may involve the site of lumpectomy/mastectomy, axilla and even proximal medial arm. The cause of persistent postsurgical pain in breast cancer patients may be attributed to various reasons, such as surgical trauma, tumor recurrence, or factors related to radiotherapy or chemotherapy.

Despite a number of studies investigating risk factors, almost all of the information has originated from single center studies and often focuses on only a few elements. Additionally, surgical approaches and analgesic regimens have changed in recent years, therefore limiting the interpretation of previous studies. Yet, tools to identify those at high risk and preventive interventions are still lacking.

Dr. Habib and his team of investigators propose to study the risk factors related to persistent postsurgical pain in breast cancer patients, and to develop a prediction model that could serve as a screening tool for patients at high risk of developing persistent pain after breast cancer surgery. Pre-existing pain and severe postoperative pain have been predictors of persistent pain after surgery, but a complete understanding on the development of persistent pain is still lacking. A major challenge facing progress in this field has been the wide variation in patient experience of pain after similar types of surgery and the inability to identify individuals who are more likely to experience severe pain after surgery. A better understanding of the risk factors of postsurgical pain will help identify the subset of patients who are likely to develop severe acute pain and persistent pain. This could help in targeting those high-risk patients with focused perioperative interventions that could reduce their risk of developing severe acute pain and persistent pain.

Chris KeithDivision Chief Awarded Duke-Singapore Collaborative Grant
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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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Duke Anesthesiology Career Service Awards

Duke Anesthesiology proudly recognizes members of the department who have demonstrated outstanding service and dedication to Duke! We thank them for their commitment to this team and the patients we serve!

Janet E. Goral

Narda Croughwell
Dianne L. Scott

Robin B. Coleman
Gary W. Massey

Christine Eaton
Nancy W. Knudsen
Jonathan B. Mark
Mark F. Newman

Jennifer Parsons
Allison K. Ross
E. June Santa
Christopher Young

Patricia M. Allushuski
Maurice L. Begin
John B. Eck

Nancy M. Kota
John F. Pierce
Melanie M. Sennett

Laura L. Booth
Karen Clemmons
Stuart A. Grant
Victoria Grossman
Paula Hawkns

Katharine S. Heinkel
Carrie A. Hines
William P. Norcross
Caswell S. Patmore

Earl S. Ransom
Jennifer Sanford
Cheryl J. Stetson
Marcy S. Tucker

Debra T. Allen
Wendy Bush
Natalie S. Clarke
Brian J. Colin
Sonia B. Crabtree
Charles E. Creel

Allan S. Fabito
Ilene B. Farkas
Patricia P. Fletcher
Stephen M. Melton
Sarah Miller
Timothy E. Miller

Allison Mooney
Michael A. Neal
Srinivas Pyati
Aaron J. Sandler
Mark W. Schontz
Erlinda Yeh

Rory Camasura
Shannon Currie
Jennifer Dominguez
Jennifer Easterling
Eric Ehieli
Lisa M. Einhorn
Reginald Enierga
Merrie Gough
Kirk Hamilton
Scott Helms

Lori A. Hester
Ru-Rong Ji
Amber Johnson
Courtney H. Kalkhof
Kelly A. Machovec
Erin Manning
Janina Marcenaro
Karen McCain
Collins Mogbo

Rachel E. Morales
Jennifer Neifeld
Karthik Raghunathan
Richard Runkle
Zaneta Y. Strouch
Dharamdeo Surujpaul
Zebulon Thomeczek
Elizabeth Wilder
Magan Zani

Chris KeithDuke Anesthesiology Career Service Awards
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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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Dr. Zhang Wins Poster Award at Inaugural Pain Meeting

Dr. Zhang with is award winning poster.

Duke Anesthesiology’s Xin Zhang, MD, PhD, received an award for “Outstanding Poster” at the first Translational Pain Research Symposium, held on June 21 – 23 at Duke Kunshan University in China. His poster is titled, “Activation of peripheral β2 and β3ARs leads to increased nociceptor activity.”

Zhang and Nackley China June 2017

Drs. Zhang and Nackley

As noted in the abstract, Dr. Zhang’s research shows that i) COMT inhibition leads to pain sensitivity, in line with increased ERK phosphorylation in DRG neurons and strengthened nociceptor activity in response to noxious stimuli, ii) COMT-dependent increases in pain sensitivity and nociceptor activity are driven by peripheral β2- and β3ARs, and iii) treatments targeted towards peripheral β2- and β3ARs and downstream effectors may prove useful in the management of functional pain syndromes. The team of investigators includes Duke Anesthesiology’s Andrea Nackley, PhD, Seungtae Kim, MD, PhD, and Sandra O’Buckley.

Dr. Zhang is a postdoctoral fellow with The Nackley Lab, part of Duke Anesthesiology’s Center for Translational Pain Medicine which is dedicated to unraveling the causes of painful conditions to better improve patient care. The Translational Pain Research Symposium was held on the new state-of-the-art campus of Duke Kunshan University. The goals of the conference were to present recent advances in basic science research of pain mechanisms, introduce cutting-edge techniques in pain research, and bridge the gap between basic research and clinical applications.

Chris KeithDr. Zhang Wins Poster Award at Inaugural Pain Meeting
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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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