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

Stacey HiltonDr. Ji Named a Highly Cited Researcher
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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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In Remembrance of Dr. William Maixner

William Maixner, DDS, PhDIt is with profound sadness that we inform you about the passing of a beloved member of our Duke Anesthesiology family, William “Bill” Maixner, DDS, PhD. He passed away on November 2 at the age of 68 after battling an illness. Duke flags were lowered on November 4 in honor of his life and legacy.

Dr. Maixner, the Joannes H. Karis, MD, Professor of Anesthesiology, was a world-renowned pioneer in pain research and one of our department’s most distinguished faculty. He will be remembered as an extraordinary leader, innovator, scientist and mentor who dedicated his life-long career to unraveling the mysteries of chronic pain and was committed to translating basic discoveries into novel diagnostics and treatments to positively impact research, education and patient care.

On January 1, 2016, Dr. Maixner joined our department from the School of Dentistry at the University of North Carolina at Chapel Hill (UNC-CH), where he was the Mary Lily Kenan Flagler Bingham Distinguished University Professor, to further expand our clinical and research program in pain medicine. During his short time with us here at Duke, he achieved incredible milestones. Dr. Maixner developed and led the Center for Translational Pain Medicine, which recently received the rare and prestigious designation as a National Center of Excellence through an $8.5 million National Institutes of Health (NIH) program project grant (PPG), the first PPG in 40 years awarded to our department. He was a visionary who brought to fruition a center that united leading basic scientists, clinicians and clinical researchers under one umbrella, with the core mission of developing novel pain therapies to improve patient care. Through his leadership, this center has rapidly become internationally-recognized as a best-in-class translational pain medicine program, ultimately transforming the way we diagnose and treat painful conditions. He was also instrumental in developing Duke Innovative Pain Therapies, a first-of-its-kind multispecialty pain practice focused on non-opioid therapies, which opened its doors to patients in September 2016. In 2017, Dr. Maixner received one of the highest honors in academia with his appointment as the Joannes H. Karis, MD, Professor of Anesthesiology, designated by the Duke University School of Medicine, becoming only the fifth faculty member in our department to be named a distinguished professor. This endowed professorship recognized his remarkable achievements in advancing medical science, significantly shaping the field of pain research and education, profoundly impacting patient care and exemplifying superior mentorship. That same year, he was named our department’s vice chair for research.

Dr. Maixner was originally from Ottumwa, Iowa. After completing his BA, PhD, and DDS at the University of Iowa, he became a research fellow at the National Institute of Dental Research. He went on to become faculty at UNC-CH, where over the span of 30 years, he served as a professor in the Departments of Endodontics and Pharmacology, co-director of the Oral and Maxillofacial Pain Program, associate dean for academic affairs in the School of Dentistry, and director of the Center for Pain Research and Innovation.

Dr. Maixner played a key role as a knowledge leader in the field of pain; he served as president of the American Pain Society and on our nation’s Health and Human Services Interagency Pain Research Coordinating Committee and the NIH’s Pain Consortium, in which he helped shape the direction of our nation’s national strategies in pain research, education and patient care. He considered chronic pain to be a “hidden epidemic” and proudly campaigned for more research support amongst colleagues, sponsors, health organizations, and congressional committees.

Dr. Maixner earned several accolades throughout his career, including the New York College of Dentistry Distinguished Scientist Award and the Wilbert E. Fordyce Clinical Investigator Award from the American Pain Society. His primary research focus was on biological, environmental and genetic factors involved in pain transmission and modulation. Notably, Dr. Maixner was the principal investigator on the National Institute of Dental and Craniofacial Research’s (NIDCR) $19 million, seven-year OPPERA study to examine pain produced by temporomandibular joint and muscle disorders. In 2012, the NIDCR awarded him and his team an additional $16 million in funding to support the study (called OPPERA II) for an additional five-year period. He published more than 200 manuscripts and book chapters and was continuously funded by the NIH since 1986.

Additionally, Dr. Maixner was appointed as a member of the Foundation for Anesthesia Education and Research Academy of Research Mentors in Anesthesiology. His mentorship skills were evidenced by the success of the numerous students, trainees and mid-career scientists whom he mentored throughout his career.

Dr. Maixner’s legacy of innovation within all three pillars of research, education and patient care will forever be remembered here at Duke as we continue to honor his accomplishments and grow his goals. Most importantly, his legacy will live through his family. He was a dedicated and loving husband to his wife, Viravan, father to his two children, William and Dylan, and grandfather to two granddaughters born earlier this year.

Please join us in extending our sincerest condolences to Dr. Maixner’s family, friends and colleagues. At the request of the family, in lieu of flowers, memorial gifts may be made to our DREAM Campaign in support of research through the DREAM Innovation Grants.

Stacey HiltonIn Remembrance of Dr. William Maixner
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