Dr. Terrando Receives Prestigious R01 Award

Niccolo Terrando, PhDThe National Institutes of Health/National Institute on Aging (NIH/NIA) has awarded Duke Anesthesiology’s Niccolò Terrando, BSc, DIC, PhD, a five-year, $2,815,756 R01 Award for his project, titled “Neurovascular dysfunction in delirium superimposed on dementia.”

Millions of Americans live with dementia and require common surgical interventions, such as orthopaedic surgery. According to the research statement, these potentially life-saving procedures often increase the risk for further cognitive deterioration and in many cases, even death. Dr. Terrando with his team of investigators at Duke University (Carol Colton, Gurpreet Baht, William Wetsel, Zhiquan Zhang, and Miles Berger) and University of Rochester Medical Center (Harris Gelbard) will address this public health concern by providing fundamental knowledge expected to help reduce the burdens of neurologic complications after common surgical procedures, and improve the quality of life for these high-risk patients.

The rationale for the proposed research is that successful completion of these studies will advance and expand the understanding of how surgery affects the blood-brain interface, and will provide new insights into molecular mechanisms of relevance to delirium, neurodegeneration and aging. Such knowledge is highly significant because it has the potential to improve surgical outcomes and quality of life for millions of vulnerable, elderly patients in the United States by using new therapeutic approaches tested in this grant.

As stated in the project’s abstract, impaired cognitive function after common surgical procedures is a growing concern, especially among the more than five million people in the nation who suffer from dementia, including Alzheimer’s disease (AD), and thus have a three-fold increased risk for fracture requiring surgical repair. After orthopaedic surgery, acute changes in cognitive function, often referred to as postoperative delirium, occur in up to 89 percent of patients with preexisting dementia, and associate with poorer prognosis and even two-fold greater risk for one-year mortality compared to patients without dementia or delirium. This proposal will attempt to model postoperative delirium superimposed on dementia after orthopaedic surgery using innovative approaches to understand, and possibly attenuate, the effects of surgery on the blood–brain interface, including the neurovascular unit (NVU) and the blood-brain barrier (BBB).

The long-term goal of Dr. Terrando and his team of investigators is to define the mechanisms that underlie surgery-induced cognitive dysfunction, and to provide safe and effective approaches to reduce this potentially devastating complication.

Dr. Terrando joined Duke in 2015 and is an assistant professor in anesthesiology, the director of the Neuroinflammation and Cognitive Outcomes Laboratory, a collaborator of Duke Anesthesiology’s Center for Translational Pain Medicine and a 2016 DREAM Innovation Grant (DIG) recipient for his research project, titled “The Systemic Milieu and its Role in Postoperative Cognitive Dysfunction.”

Chris KeithDr. Terrando Receives Prestigious R01 Award
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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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Taylor Appointed Finance Director

Sharon TaylorWe are pleased to announce that Sharon Taylor has been appointed as the finance director of Duke Anesthesiology’s business office. This position was previously held by Dan Marcantonio who retired from the department earlier this month. In her new role, Taylor will oversee the finance unit which is comprised of accounting and finance staff and is responsible for the financial management of departmental revenue and expenses.

Taylor came to Duke 24 years ago from the banking industry and began her career on the university side in Duke Financial Services working for corporate payroll. She worked her way to accounting supervisor for the general ledger team where she was responsible for the monthly and fiscal year-end close for the institution. She then moved to the SAP implementation team, now known as Administrative Systems Management, where she developed key finance tools that are still being used today.

After spending a few years as assistant finance manager in the Department of Medicine, Taylor helped develop a Research Costing and Compliance program, known today as the Research Administration Academy certificate program. In 2009, Taylor joined Duke Anesthesiology where she has been responsible for managing the finance team in its day-to-day operations, leading the Research Administrators Leadership Team, and assisting the grants team with operational and financial oversight.

Taylor has two sons, Jarrett and Eric. In her free time, she enjoys spending time with her grandson and baking. Please join us in congratulating Taylor on her new role in the department.

Chris KeithTaylor Appointed Finance Director
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