Dr. Mathew Awarded Multi-PI NIH Grant for “NOGGIN” Study with Dr. Piccini from Cardiology

Joseph P. Mathew, MD, MHSc, MBA

Joseph Mathew, MD, MHSc, MBA

The National Institutes of Health has awarded Duke Anesthesiology chairman, Joseph Mathew, MD, MHSc, MBA, Jerry Reves, MD, Professor of Anesthesiology, a $3,739,083 R01 grant for his project titled, “Neurocognition and Greater Maintenance of Sinus Rhythm in AF (NOGGIN AF).”

Atrial fibrillation (AF), a very common heart rhythm disorder, especially in older adults, increases the risk for a decline in cognitive function and the development of dementia. While the mechanisms by which atrial fibrillation result in brain injury are not well understood, it is also unknown whether restoring regular heart rhythm using a technique called catheter ablation (a minimally invasive procedure in which the doctor advances a flexible thin tube through the blood vessels to the heart to stop abnormal electrical signals in the heart tissue) reduces the likelihood of developing cognitive decline or dementia.

Jonathan P. Piccini, MD, MHS, FACC, FAHA, FHRS

Jonathan P. Piccini, MD, MHS, FACC, FAHA, FHRS

The R01 is a multi-PI grant with Dr. Jonathan Piccini of Duke’s Department of Medicine. In the proposed study, they will determine whether restoring regular heart rhythm using catheter ablation leads to less long-term brain damage and dysfunction than using medications alone. The study is expected to vertically advance the field of AF management by revolutionizing the understanding of the mechanisms by which AF induces cognitive decline, and by providing an important and necessary step toward justifying rhythm control by catheter ablation as a strategy to arrest the processes that lead to cognitive impairment and dementia.

Mathew and Piccini will test the hypothesis that among AF patients receiving oral anticoagulation, restoration of sinus rhythm with catheter ablation vs drug therapy leads to less long-term neurologic damage and dysfunction due to improved cerebral blood flow and lower risk for additional ischemic injury. The primary aims of the prospective, observational clinical trial in AF patients treated with catheter ablation vs drug therapy are to compare structural cortical characteristics, cerebral blood flow, and cognitive function; and assess the relationship between neurologic outcomes and plasma and imaging biomarkers of coagulation and inflammation.

This is the first study to incorporate a comprehensive neurocognitive test battery, structural and functional neuroimaging, cerebral blood flow assessment, and plasma and imaging biomarkers to a) better delineate the contribution of each of the known risk factors to the development of cognitive decline in patients with AF, and b) assess how restoration of sinus rhythm using catheter ablation vs drug therapy may alter the trajectory of cognitive decline and development of dementia.

The long-term goals of this study are to understand the interaction between heart rhythm and neurologic health, and to investigate methods to prevent cognitive dysfunction due to AF.

Stacey HiltonDr. Mathew Awarded Multi-PI NIH Grant for “NOGGIN” Study with Dr. Piccini from Cardiology
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Dr. Vorenkamp Named Recipient of Presidential Scholar Award

Kevin Vorenkamp, MDThe American Society of Regional Anesthesia and Pain Medicine (ASRA) has named Duke Anesthesiology’s Kevin Vorenkamp, MD, FASA, as the recipient of its Presidential Scholar Award; it recognizes members who have demonstrated outstanding scientific and sustained contributions to regional anesthesia and pain medicine in the last 10 years.

ASRA members nominate mid-career, qualified anesthesiologists whose research has had or will have meaningful impact on the clinical practice or scientific direction of regional anesthesia and/or pain medicine.

“I am greatly honored to receive the 2021 ASRA Presidential Scholar Award. ASRA has remained a major influence in my education, growth and development over the past 15 years. It was my initial exposure to regional anesthesia that reinforced my desire to shift my career planning from orthopedic surgery to anesthesiology and eventually pain medicine,” says Vorenkamp, associate professor of anesthesiology and chief of Duke Anesthesiology’s Pain Medicine Division. “As my personal career trajectory has shifted into areas of coding, compliance and advocacy focus, I have been pleased to see that ASRA has expanded its mission to include advocacy to support its members and preserve our impactful treatments to relieve the global burden of pain.”

In addition to his scholarly work, Vorenkamp previously served as the American Society of Anesthesiologists (ASA) advisor to CPT prior to his appointment to the American Medical Association’s CPT Editorial Panel in 2015. He is currently serving his second four-year term. He also serves as the ASA delegate to the Multisociety Pain Workgroup and is the vice-chair of the ASRA Practice Management Committee. At Duke, he also serves as the medical director of the Duke Raleigh Hospital Pain Clinic and the associate director of Patient Safety and Quality Improvement. He will be presented the Presidential Scholar Award at ASRA’s annual meeting this fall.

Stacey HiltonDr. Vorenkamp Named Recipient of Presidential Scholar Award
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Dr. Achanta Awarded NIH Grant for Countermeasures Research

Satya Achanta, DVM, PhD, DABTThe National Institutes of Health’s National Institute of Environmental Health Services has awarded Duke Anesthesiology’s Satya Achanta, DVM, PhD, DABT, a two-year, $442,750 R21 grant for his project, titled “Inhibition of Soluble Epoxide Hydrolase Protects Against Phosgene-Induced Lung Injuries.”

The toxic effects of phosgene gas were first reported in 1899 by a group of anesthesiologists and surgeons due to the conversion of chloroform to phosgene. In modern times, phosgene is widely used as a chemical intermediate in the chemical manufacturing of pharmaceuticals, polymers, dyes, and other products. Despite the use of phosgene as a chemical weapon since World War I, there is no effective antidote.

Phosgene gas-exposed victims experience chest tightness and shortness of breath at about six to eight hours after inhalation, with progressive hypoxia and severe pulmonary edema leading to high mortality. The recovered individuals may experience long-term symptoms such as airway and pulmonary remodeling, and asphyxia. Currently, symptomatic treatment is provided to victims. Therefore, phosgene gas remains an important threat, potentially released in industrial accidents, diverted, or synthesized by terrorist groups.

In the funded proposal, Achanta and his team will identify and test novel therapeutic drugs that inhibit factors contributing to pulmonary injury and promote the resolution of the injury. The project is part of the portfolio of NIH’s Countermeasures against Chemical Threats (CounterACT) Program, a trans-agency initiative launched by the Department of Health and Human Services after the 9/11 attacks to improve the nation’s preparedness and to engage academia in countermeasures research. Achanta made significant contributions to the medical countermeasures research over the past nine years, in collaboration with Duke Anesthesiology’s Dr. Sven-Eric Jordt.

Stacey HiltonDr. Achanta Awarded NIH Grant for Countermeasures Research
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Dr. Devinney Awarded Grant for Aging and Delirium Research

Michael Devinney, MD, PhDThe National Institutes of Health’s National Institute on Aging has awarded Duke Anesthesiology’s Michael Devinney, MD, PhD, a two-year, $322,000 R03 GEMSSTAR grant for his project, “The Association of Blood-Brain Barrier Breakdown with Sleep Apnea and Postoperative Delirium.”

Postoperative delirium is a fluctuating disturbance in attention and consciousness associated with increased postoperative mortality and decreased quality of life that occurs in up to 40 percent of the more than 19 million older Americans who undergo surgery every year. Despite the substantial distress, morbidity and mortality associated with delirium, there are not any FDA-approved drugs to prevent or treat delirium because we know very little about its underlying pathophysiology. One possible mechanism of postoperative delirium is blood-brain barrier (BBB) breakdown, which occurs in older adults after anesthesia/surgery. However, no human studies have actually determined whether increased BBB breakdown is associated with postoperative delirium, nor have we identified treatable risk factors to prevent BBB breakdown or delirium.

One highly prevalent, frequently undiagnosed but treatable disorder in older surgical patients is sleep apnea. Sleep apnea has been associated with increased risk of dementia and Alzheimer’s disease, but it is unknown to what extent sleep apnea is associated with increased BBB breakdown. Thus, the aim of Devinney’s study is to determine the extent that increased BBB breakdown is associated with sleep apnea and postoperative delirium, which will provide insight on mechanisms of sleep apnea-related cognitive dysfunction and postoperative delirium. Overall, the findings from this study are expected to inform efforts to devise novel therapeutic interventions to prevent postoperative delirium and longer-term cognitive dysfunction such as dementia and Alzheimer’s disease in older adults.

“I really owe the success of this grant to my excellent mentors, research team, and the great institutional support and environment in our department and the Critical Care Medicine Division at Duke,” says Devinney, assistant professor of anesthesiology. “Over the course of my career, my goal is to develop interventions for delirium, because we currently have very few treatment options to prevent or treat delirium in older surgical patients. I am grateful for this R03 GEMSSTAR award, as it will provide crucial support to begin establishing myself as an independent aging and delirium researcher in critical care anesthesiology.”

Stacey HiltonDr. Devinney Awarded Grant for Aging and Delirium Research
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Grant Awarded for Immunoprofiling Study

Niccolò Terrando, BSc (hons), DIC, PhD

Niccolò Terrando, BSc (hons), DIC, PhD

The National Institutes of Health’s National Institute on Aging has awarded Duke Anesthesiology’s Niccolò Terrando, PhD, and University of Rochester’s Harris Gelbard, MD, PhD, a $239,843 multi-PI R21 grant for their project, “Immunoprofiling Postoperative Delirium During Aging and Neurodegeneration.”

Millions of elderly Americans live with cognitive impairment and require common surgical interventions, such as orthopedic surgery, that are frequently accompanied by delirium in the postoperative period. The proposed research will address this serious public health concern by providing key data about immune cell populations that are the likely cause of this type of delirium. This will help Terrando and Gelbard develop new therapies that target these immune cells for these high-risk patients.

With the R21 award, they will explore the use of the technique of mass cytometry (CyTOF) that is available through the Gelbard lab to identify immune cell subsets that mediate neuroinflammation in the central nervous system (CNS) using a well- established orthopedic mouse model of postoperative delirium developed by Terrando’s Neuroinflammation and Cognitive Outcomes Laboratory. This represents an ever-growing collaboration between these two labs, which over the past five years have been tackling questions on how surgery, and more recently infection akin to COVID-19, affect the vulnerable brain. “We are thrilled to be working with Dr. Gelbard and his team to expand our understanding on how surgery engages the immune system in contributing to complications such as delirium,” says Terrando, associate professor in anesthesiology.

Harris Gelbard, MD, PhD

Harris Gelbard, MD, PhD

Dysregulated immunity is a hallmark of normal aging; it is also recognized as a key feature of many neurological disorders, including dementia and perioperative complications like delirium as recently reviewed in Nature Immunology. No study has yet attempted to unbiasedly profile the immune subset specific response to orthopedic surgical trauma in the CNS. Terrando and Gelbard will conduct two specific aims: (1) to define how age differences between young adult and elderly male and female mice modulate immune cell subsets in the CNS and blood after orthopedic surgery; and (2) to determine the impact of Alzheimer’s (AD)-like pathologic features using 5xFAD transgenic male and female mice (an accelerated model to study key aspects of neurodegeneration) on immune cell subsets in the CNS and blood after orthopedic surgery. The ability to resolve immune cell subsets and align them with discrete repertoires of pro-inflammatory signaling molecules with CyTOF will be key to understanding whether delirium results from neuroinflammation due to peripherally migrating and/or CNS-resident immunocytes.

Findings from this research are expected to have an important, positive impact on the ADRD field to reduce the impact of delirium and dementia in the aging population by helping identify patients at greater risk for developing delirium and delirium superimposed on dementia. “We are grateful for the continuous support by the National Institute on Aging to advance this field of research,” adds Terrando.

Stacey HiltonGrant Awarded for Immunoprofiling Study
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