Dr. Terrando Awarded Grant to Study Delirium Therapy

Niccolò Terrando, BSc (hons), DIC, PhDExalys Therapeutics has awarded Duke Anesthesiology’s Niccolò Terrando, PhD, a $200,479 grant for his project, “Test the Efficacy of Exalys EP4 Antagonist to Prevent Neuroinflammation and Delirium in a Preclinical Model.” The project will study the efficacy and safety of Exalys’ lead Prostaglandin E2 receptor 4 (EP4) antagonist in preventing cognitive decline (inattentiveness) and associated inflammatory biomarkers in a surgical preclinical model of delirium (orthopedic fracture). Results from this study could advance the development of a new immune-drug target to combat delirium. Terrando and Dr. Ting Yang of Duke Medicine serve as co-principal investigators.

Postoperative delirium, also referred to as “acute brain failure,” is a common and serious surgical complication in older patients that can lead to increased hospital costs and poor post-discharge outcomes. The ongoing pandemic due to COVID-19 has further highlighted the multiple challenges related to treating patients with delirium, especially given the limited therapeutic options available. Despite the prevalence of delirium in multiple settings, ranging from critical illness to elective surgical procedures, there are currently no therapies to possibly prevent delirium.

Delirium is a challenging, multifactorial pathology, with several mechanisms impacting the brain functioning of vulnerable patients. The Neuroinflammation and Cognitive Outcomes Laboratory, directed by Terrando at Duke Anesthesiology, has identified a critical role of systemic inflammation in driving “acute brain failure” and causing pathologic and behavioral changes in rodent models that resemble features of human delirium.

“Inflammation truly is a double edge sword in the setting of perioperative recovery,” says Terrando, associate professor in anesthesiology. “We know many of the deleterious effects that pro-inflammatory molecules can exert on the brain. We also know that blocking these molecules can impair the recovery of postoperative patients, for example by impairing healing.” Yang and Terrando recently contributed a review in Nature Immunology discussing the role of innate immunity in driving perioperative neurocognitive disorders, such as delirium.

“We are thrilled for the opportunity provided by Exalys to test and expand the potential application of this new compound to prevent delirium,” Yang adds. Her laboratory is actively studying the role of EP4 signaling in cardiovascular disorders, including hypertension and brain inflammation.

Stacey HiltonDr. Terrando Awarded Grant to Study Delirium Therapy
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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. Ji Named a Highly Cited Researcher

Ru-Rong Ji, PhDDuke Anesthesiology’s Ru-Rong Ji, PhD, distinguished professor of anesthesiology, has once again been named among the most “Highly Cited Researchers” in the world. Ji is one of 37 Duke faculty named to the list this year; he is one of 22 faculty from the Duke University School of Medicine.

The annual list is based on the number of highly cited papers produced over an 11-year period from January 2009 to December 2019. Citation rate, as tracked by Clarivate’s Web of Science, is an approximate measure of a study’s influence and importance. 6,127 researchers from 60 countries are recognized by the 2020 listing.

Ji was one of 54 Duke researchers who made the global list of “Highly Cited Researchers” in 2019; a list he also made in 2018. His research focuses on molecular and cellular mechanisms of chronic pain, including but not limited to mediators of inflammation and pain, neuropathic pain and cancer pain.

“This list is very dynamic from year to year,” says Ji, director of the Sensory Plasticity and Pain Research Laboratory and co-director of the Center for Translational Pain Medicine at Duke Anesthesiology. “I am very pleased that someone from anesthesiology can make the list. I am proud to represent the field, and I appreciate the strong support for my research from the department.”

The year’s most highly cited authors from the Duke University School of Medicine are: 

Robert M. Califf—Clinical Medicine
Avshalom Caspi—Psychiatry and Psychology
Jane Costello— Psychiatry and Psychology
Lesley H. Curtis—Clinical Medicine
Geraldine Dawson— Cross-Field
Pamela S. Douglas—Clinical Medicine
Charles A. Gersbach—Cross-Field
Christopher Bull Granger—Clinical Medicine
Barton F. Haynes—Immunology and Microbiology
Adrian F. Hernandez—Clinical Medicine
Ru-Rong Ji—Cross-Field
Robert J. Lefkowitz—Clinical Medicine
Sarah H. Lisanby—Cross-Field
Jason Locasale— Cross-Field
Edward A. Miao—Immunology
Terrie E. Moffitt—Psychiatry and Psychology
Kristen Newby—Clinical Medicine
Christopher B. Newgard—Cross-Field
Erik Magnus Ohman—Clinical Medicine
Manesh R. Patel—Clinical Medicine
Michael J. Pencina—Social Sciences and Clinical Medicine
Eric D. Peterson—Clinical Medicine

For a complete list of Duke faculty, see the article at Duke Research Blog.

Source: Duke Med School Blog, November 19, 2020

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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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Duke University Hospital Program Earns Distinguished Three-Star Ratings

By Tracey Koepke, Duke Heart Center

We are pleased to share with you that our Adult Cardiac Surgery program at Duke University Hospital has, for the first time, earned three simultaneous distinguished three-star ratings from The Society of Thoracic Surgeons (STS) for its patient care and outcomes in the following areas: isolated coronary artery bypass grafting (CABG) procedures; isolated aortic valve replacement (AVR) surgery, and isolated mitral valve replacement and repair (MVRR) surgery. The three-star rating, which denotes the highest category of quality, places our program among the elite for CABG, AVR and MVRR in the U.S.

“This is a significant validation of the quality and performance that we are able to deliver in cardiac surgery — the three-star rating means that our outcomes are in the top 10 percent of all centers in the United States,” said Peter K. Smith, MD, chief of the division of Cardiovascular and Thoracic Surgery and co-director of Duke Heart Center. “That we have achieved this within each of the three most important domains of cardiac surgery — bypass surgery, aortic valve replacement, and mitral valve repair or replacement – is a tribute not just to the surgeons but our entire team of dedicated health care professionals in our Operating Room, Intensive Care Unit, and Step-down Units.”

The STS star rating system is one of the most sophisticated and highly regarded overall measures of quality in health care, rating the benchmarked outcomes of cardiothoracic surgery programs in the U.S. The star rating is calculated using a combination of quality measures for specific procedures performed by an STS Adult Cardiac Surgery Database (ACSD) participant. We achieved a two-star rating in each of the remaining two areas of reporting: AVR+CABG and MVRR+CABG.

“Any scoring system has its limitations, but this is one of the most scientifically validated systems for heart surgery. It involves a huge amount of data from almost all centers in the U.S. and a very complicated and well thought out risk-adjustment model,” according to Carmelo Milano, MD, Chief of the Section of Adult Cardiac Surgery in the division of Cardiovascular and Thoracic Surgery. “Not only are they looking at raw outcomes like survival, but they take into consideration the pre-operative conditions that may make certain cases much higher risk. This is a very well respected grading system for heart surgery.”

The latest analysis of data for CABG covers a 1-year period, from January 2019 to December 2019; the analysis of data for isolated AVR, isolated MVRR, AVR+CABG and MVRR+CABG surgeries covers a 3-year period, from January 2017 to December 2019.

Mihai V. Podgoreanu, MD

Mihai V. Podgoreanu, MD

“Achieving the elite STS three-star rating, one of the most sophisticated and highly regarded overall measures of quality in health care, is a testament to our program’s commitment to quality improvement and safety across the cardiac surgical patient journey – from careful preoperative planning and optimization, to relentless attention to detail and coordination of intraoperative and postoperative decision making among multi-disciplinary heart team members,” added Mihai Podgoreanu, MD, chief of Cardiothoracic Anesthesiology and Critical Care. “In these unprecedented times, we are united in our dedication, resilience, compassion, and innovative spirit to continue pursuing our highest purpose – excellence and quality care for patients in need of cardiac surgery and their families.”

“As an organization and a group – the STS three star rating is evidence of the dedication of our entire Heart Center around how we care for our patients with multi-disciplinary teams that start with the evaluation and identification of patients needing coronary revascularization or valve surgery all the way through recovery, rehab, and return to life,” said Manesh Patel, MD, chief of the division of Cardiology and co-director of Duke Heart Center. “I am excited that during these challenging times our teams have continued the dedication and work to stay focused on patient outcomes.”

The STS National Database was established in 1989 as an initiative for quality improvement and patient safety among cardiothoracic surgeons. The STS ACSD houses approximately 6.9 million surgical records and gathers information from more than 3,800 participating physicians, including surgeons and anesthesiologists from more than 90 percent of groups that perform heart surgery in the US. The Database includes three other components: the Congenital Heart Surgery Database (CHSD), the General Thoracic Surgery Database (GTSD), and the mechanical circulatory support database (Intermacs). Duke has participated in the STS National Database since its inception.

Stacey HiltonDuke University Hospital Program Earns Distinguished Three-Star Ratings
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