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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Dr. Terrando Awarded Grant for COVID-19 Related Research

Niccolò Terrando, BSc (hons), DIC, PhDThe National Institutes of Health has awarded Duke Anesthesiology’s Niccolò Terrando, BSc, DIC, PhD, a one-year, $322,620 supplement grant to his R01-funded project, titled “Delirium Superimposed on Dementia Intersects with COVID-19.”

Delirium has become a common complication of COVID-19 that further impairs the recovery of already debilitated patients, in particular older adults. Terrando and his co-investigators are studying the role of neuroinflammation as a putative driver of delirium pathogenesis. For this supplement, they will explore how lung injury, akin to COVID-19 infection, leads to delirium by impairing the blood-brain barrier and triggering immune cell trafficking into the brain.

Terrando aims to develop a model of COVID-19 lung injury that activates the immune system to damage the brain, affecting areas that serve attention, memory, and thinking, and reverse these changes with an experimental drug in development. Findings from this research supplement will address this serious public health concern by providing fundamental knowledge on the pathogenesis of delirium following COVID-19-like infection. Such work has the potential to reduce the health care burden of COVID-19 associated with delirium and related neurologic complications, such as Alzheimer’s disease and related dementias (ADRDs).

“We are thrilled to develop this project in collaboration with Dr. Purushothama Rao Tata in the Duke Department of Cell Biology, an expert in murine lung injury models, and Dr. Harris A. Gelbard in the Center for Neurotherapeutics Discovery at the University of Rochester Medical Center that developed new therapeutics effective in resolving neuroinflammation, which we are currently testing in the R01 funded project,” says Terrando, associate professor in anesthesiology. “We are grateful for the National Institute on Aging’s continuous support, and we are looking forward to providing timely results that may curtail pathologic hallmarks of delirium and neurodegeneration resulting from COVID-19.”

Stacey HiltonDr. Terrando Awarded Grant for COVID-19 Related Research
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Duke Anesthesiology Awarded Program Project Grant

The National Institutes of Health (NIH) has awarded Duke Anesthesiology a five-year, $8,566,593 million Center of Excellence award that is supported via the NIH’s Program Project Grant (PPG) mechanism. This is of substantial significance to the department and university because it marks the funding of a new national center and represents the first PPG to the department in 40 years.

The designation as a Center of Excellence within Duke Anesthesiology’s Center for Translational Pain Medicine (CTPM) by the National Center for Complementary and Integrative Health (NCCIH) brings this department both national and international recognition; there are only 1-3 Centers of Excellence funded as PPGs by NCCIH in the country. The new center represents a new and unique resource to investigators world-wide who have interest in translational pain research; it represents a nidus that not only advances Duke Anesthesiology’s mission in translational pain research, but brings it increased visibility in the pain field, which will further expand international collaboration and increase its value and recognition as a leader in translational pain medicine.

William Maixner, DDS, PhDWe want to sincerely thank everyone who helped drive the Center of Excellence initiative that has resulted in this extraordinary outcome. This award and designation is the culmination of a nearly three-year effort by the CTPM, initiated by the center’s co-directors, including Dr. William Maixner, who worked closely to develop the proposal with the center’s members and affiliates (*see complete list of names below).

The title of the PPG is “Resolution of Neuroinflammation and Persistent Pain by Complementary Approaches.” The overarching aims of the PPG is to identify new and novel complimentary approaches to the treatment of pain conditions. The PPG will support the intellectual development of the Center of Excellence and the infrastructure for three scientific projects and three support cores. These units will further bring together Duke Anesthesiology’s basic science and clinical groups to advance translational pain research.

*P01 collaborators: William Maixner, Shad Smith, Andrey Bortsov, Andrea Nackley, Sven-Eric Jordt, Niccolo Terrando, Luis Ulloa (Anesthesiology), Wolfgang Liedtke and Yong Chen (Anesthesiology and Neurology), Fan Wang (Neurobiology), and Staci Bilbo (Psychology and Neuroscience)

Stacey HiltonDuke Anesthesiology Awarded Program Project Grant
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Study in Mice Suggests Post-Surgical Delirium Caused by Inflammation

Niccolò Terrando, BSc (hons), DIC, PhDAlzheimer’s disease patients who undergo orthopedic or other surgeries frequently develop post-surgical delirium, often leading to a poor recovery and a higher risk of dying.

The cause of this acute disruption in the patient’s mental status is largely unknown, but previous studies have suggested a link to some intrinsic response to surgical trauma itself, the multifaceted perioperative environment, and patient-specific factors that altogether contribute to post-surgical delirium.

In a study using mice led by Duke Health researchers, a new finding suggests that inflammation, especially as it impacts the blood-brain barrier in older and more frail subjects, amplifies neurodegenerative processes and drives the development of post-surgical delirium. The study published online April 15 in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

“The blood-brain barrier has often been under-appreciated in the context of perioperative neurocognitive disorders, such as delirium,” said senior author Niccolò Terrando, Ph.D., associate professor in the Department of Anesthesiology at Duke University School of Medicine. “This study provides evidence that a systemic response to surgery triggers a series of events that enables inflammation to breach the brain’s gatekeeper.”

Terrando and colleagues studied the effects of orthopedic surgeries in older mice with the pathological features of human Alzheimer’s disease. These animals underwent an orthopedic fracture model and the researchers traced how post-surgical delirium unfolds.

Notably, inflammation disrupted the blood-brain barrier, especially in older and more vulnerable animals, and caused rapid accumulation of amyloid beta (a key protein dysregulated in the Alzheimer’s disease brain), which then altered the function of immune cells in the central nervous system, thus resulting in post-surgical delirium.

“We described a neurovascular pathology that drives the development of postoperative delirium as a result of surgical trauma, which contributes to a rapid accumulation of amyloid beta in the brain,” Terrando said. “This may represent a unique molecular signature of delirium superimposed on dementia and a potential target for interventions.”

Terrando said future studies will focus on how surgery impacts the blood-brain barrier and potential ways to curtail this neuroinflammatory response in older surgical patients and, particularly, those with Alzheimer’s disease.

In addition to Terrando, study authors include Ping Wang, Ravikanth Velagapudi, Cuicui Kong, Ramona M. Rodriguiz, William C. Wetsel, Ting Yang, Miles Berger, Harris A. Gelbard and Carol A. Colton.

The study received support from the National Institutes of Health (R01AG057525, R21 AG055877-01A1, R03 AG064260-01, K76-AG057022); the Duke Claude D. Pepper Older American Independence Center (P30AG028716); the Duke Anesthesiology Department; the Alzheimer’s Association. A full list of supporters is provided in the study.

Source: Duke Health news release (Durham, NC – April 15, 2020)

Stacey HiltonStudy in Mice Suggests Post-Surgical Delirium Caused by Inflammation
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Postdoctoral Associate Awarded Prestigious Grant

Ravikanth Velagapudi, PhDThe Network for Investigation of Delirium Unifying Scientists (NIDUS) has awarded Duke Anesthesiology’s Ravikanth Velagapudi, PhD, a 2019-2020 NIDUS Junior Investigator Pilot Award (12-month, $80,500 grant) for his proposal titled, “Profiling Postoperative Neuroinflammation in a Mouse Model of Delirium Superimposed on Parkinson’s Disease.”

Velagapudi’s proposal was selected through a rigorous review process from a pool of highly-competitive applications. His project will help gain fundamental knowledge on the impact of surgery on preclinical Parkinson’s disease (PD) models. Currently, millions of Americans live with PD and routinely undergo common surgical procedures, such as orthopedic surgery. Although lifesaving, surgery can increase the risk for cognitive complications like delirium, which in many cases associate with worse prognosis, increased health care costs, and even death. This is especially concerning in frail subjects and older adults who already suffer from ongoing neurodegeneration, such as Alzheimer’s disease, but also PD. This specific project will explore the effects of surgery-induced postoperative neuroinflammation in a genetic PD mouse model. Results from these experiments will provide novel understanding on how surgical trauma synergizes with PD pathology and may lead to novel therapeutic targets to treat delirium in subjects with ongoing PD pathology.

“It is a great opportunity to receive this pilot award from NIDUS under the junior investigator track to study delirium in PD,” says Velagapudi. “To date, this is a largely understudied subject, especially in the context of preclinical models and signaling mechanisms. In fact, few studies so far have addressed the effects of delirium on PD.” This pilot grant also provides a unique and timely opportunity to build a future career development research program for Velagapudi focusing on the interactions between postoperative delirium and PD-neurodegeneration.

Velagapudi is a postdoctoral associate in the Neuroinflammation and Cognitive Outcomes Laboratory in Duke Anesthesiology, led by Dr. Niccolò Terrando, who says this prestigious award is a remarkable accomplishment for his mentee. “I am very proud of Ravi’s achievement in just one year with my team. This award will provide an exceptional training opportunity and will further grow our collaboration with Dr. Laurie Sanders’ group in Duke Neurology, who are experts in PD pathogenesis.”

Velagapudi will present the findings of his project at the annual American Delirium Society meeting in 2021.

Stacey HiltonPostdoctoral Associate Awarded Prestigious Grant
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