Research Highlights from the 2021 Kosaka Best Abstract Award Winners and Finalists

Nine outstanding abstract author semifinalists, from a competitive field of more than 600 applicants, each delivered an 8-minute oral summary of their research, followed by one or two brief questions, during the Kosaka Best Abstract Awards Session on May 16 at the IARS 2021 Annual Meeting. There were three semifinalists in the Basic Science category, three in the Clinical Research category, and three in the Scholars presentation category. Four judges moderated the presentations, deliberated behind the scenes, and, at the closing of the program, announced the three finalists – one from each category. The top three award winners each received a Kosaka Award Certificate and a $500 prize, and all nine finalists received a Kosaka Award Certificate and a $50 prize.

Shufan He, PhD, from Stanford University and The Second Hospital of Anhui Medical University, was selected as the Basic Science Research Award Winner for her research on “Leveraging TRPV1 genetic divergence between avian and mammalian species to develop a TRPV1K710N knock-in mouse and a novel analgesic.” Keith M. Vogt, MD, PhD, from University of Pittsburgh, was announced as the Clinical Research Award Winner for his work on “Whole-brain network connectivity changes with midazolam sedation during task performance and periodic pain: A functional MRI study in healthy young adults.” The Scholars Presentation Award was provided to Yifan Xu, MD, PhD, from Oregon Health and Sciences University, for her research on “Modulation of Microvascular Blood Flow And Stroke Outcome Via GPR39 in Mice.”

This year’s judges were Vivianne Tawfik, MD, PhD; Seun Johnson-Akeju, MD; Max B. Kelz, MD, PhD; and Y.S. Prakash, MD, PhD. Dr. Kelz opened and closed the program with the announcement of the three finalists.  Dr. Prakash moderated the Basic Science presentations; Dr. Johnson-Akeju moderated the Clinical Research presentations; and Dr. Tawfik moderated the Scholars presentations.

The Kosaka Best Abstract Awards, sponsored jointly by the Japan Society for Clinical Anesthesia and the International Anesthesia Research Society (IARS), has been recognizing new research and investigators from around the world since 1990.

Here are brief summaries of the research from this year’s semifinalists and winners:

Basic Science Award Finalists

“Leveraging TRPV1 genetic divergence between avian and mammalian species to develop a TRPV1K^710N knock-in mouse and a novel analgesic”

Shufang He, PhD, Stanford University, Stanford, CA, and The Second Hospital of Anhui Medical University, Hefei, China

Using rats, knock-in mice, and wild type mice, this study explored whether introducing a genetically divergent avian transient receptor potential vanilloid 1 channel (TRPV1) sequence by CRISPR/Cas9, a technology for genetic manipulation, to rodents limits pain responses without exacerbating cellular injury. Findings show it is possible to achieve gene editing in the rodent TRPV1 receptor to carry a single TRPV1 amino acid that is genetically divergent between birds and mammals, and to reduce biochemical and behavioral responses to noxious stimuli in rodents. Designing a cell-permeable peptide targeting the TRPV1 region mimics the effect in rodents and creates a promising lead compound for use in developing a novel analgesic.

“Protective Effects of Hydrogen Gas against Spinal Cord Ischemia Reperfusion Injury: A Microdialysis Study in the Spinal Ventral Horn”

Aya Kimura, MD, Osaka City University Graduate School of Medicine, Osaka, Japan  

In their experimental study, investigators assessed the efficacy of hydrogen gas (H₂), as a novel neuroprotective gas against spinal cord ischemia-reperfusion injury (SCI). They also described its mechanisms by measuring glutamate concentration in the ventral horn of the spinal cord. Subjects included 36 rats in six groups: sham, SCI only, SCI + 1% or 2% or 3% H₂ inhalation; or SCI + DHK (a selective inhibitor of the glutamate transporter) + 3% H₂ inhalation. Findings show that H₂ inhalation has a protective and concentration-dependent effect against SCI. Glutamate transporter-1 plays an important role in the protective mechanism.

“Reduction in Cerebral Blood Flow During Aeromedical Evacuation-Relevant Hypobaria Following Rat Traumatic Brain Injury”

Gary Fiskum, PhD, University of Maryland School of Medicine, Baltimore, MD  

Using adult male rats, researchers tested the hypothesis that cerebral blow flow (CBF) is reduced after traumatic brain injury (TBI) and is further reduced during exposure to aeromedical evacuation (AE)-relevant hypobaria at 24 hours post injury. Results support the recommendation that TBI patients should either wait at least several days before flying or fly at cabin pressure higher than that typically used. Further, the use of high levels of supplemental oxygen should be avoided during flights as hyperoxia can worsen oxidative stress and metabolic dysfunction.

Clinical Research Award Finalists

“Whole-brain network connectivity changes with midazolam sedation during task performance and periodic pain: A functional MRI study in healthy young adults”

Keith M. Vogt, MD, PhD, University of Pittsburgh, Pittsburgh, PA

The authors conducted a secondary analysis of data from a within-subject crossover imaging study that compares midazolam (MDZ) and ketamine (KT) on multiple behavioral and imaging endpoints. Subjects included 16 healthy volunteers, ages 25.7 ± 5.3 years, with 11 males and five females having functional MRI (fMRI) under saline, followed by a target-controlled infusion of MDZ. Findings show the majority of changes in the brain are localized to nodes in the parietal posterior temporal and occipital lobes. In memory tasks, during periodic painful stimulation, light sedation with MDZ causes robust increases in background network connectivity throughout the brain with a predominance of posterior functional connectivity changes.

“Applying Machine Learning to Identify Pediatric Patients at Risk of Critical Perioperative Adverse Events: using the APRICOT Dataset”

Hannah Lonsdale, MBChB, Johns Hopkins University, St Petersburg, FL

Investigators presented a high-performance learning model for classifying patients as high or low risk for perioperative adverse events (PAEs), as a secondary use of the Anesthesia Practice in Children Observational Trial (APRICOT) dataset. Subjects included 30,874 children from 33 countries with severe critical events per APRICOT. Findings show that airway interface, inpatient status, and history of influenza are the most substantial predictive factors for severe PAEs. Individually identifying patients at low risk for critical PAEs may help clinicians identify cases with low to high likelihood of care escalation, which may help in stratifying patients for care at satellite sites.

“Reduction of preoperative anxiety using Virtual Reality vs midazolam: A randomized controlled trial”

Anthony Koo, MD, Phoenix Childrens Hospital, Scottsdale, AZ

Researchers compared the use of virtual reality (VR) to midazolam (MDZ) for reducing preoperative anxiety in surgical patients, and assessing differences in induction, emergence delirium (ED), pain scores, and opioid use. Subjects included 28 first-time surgical patients, ages 5-11 years, having tonsillectomy or tonsillectomy and adenoidectomy. They received MDZ or played an underwater-themed immersion VR game. Findings show VR is equivalent to MDZ for preoperative induction compliance. Postoperatively, patients in the MDZ and VR groups have similar ED, pain scoring, and pain medication use.

Scholars Award Finalists

“Modulation Of Microvascular Blood Flow And Stroke Outcome Via GPR39 in Mice”

Yifan Xu, MD, PhD, Oregon Health and Sciences University, Portland, OR

Researchers investigated the role of G protein-coupled receptor 39 (GPR39) in stroke using GPR39 knock-out (KO) mice. The study tested the hypothesis that GPR39 KO mice sustained a larger infarct during stroke, associated with lower microvascular reperfusion after transient local cerebral ischemia, when compared to wild-type (WT) mice with intact GPR39. Optical imaging showed decreased red blood cell flux in deeper cortical layers after occlusion and KO mice having decreased microvascular reperfusion in cortical layers when compared to WT mice. This suggests that GPR39 plays a protective role in ischemic stroke, making it a potential therapeutic target.

“Perioperative neurocognitive and neuroimaging trajectories in older APOE4 carriers vs non-carriers: A prospective cohort study”

Rosa O. Yang, MS, Duke University School of Medicine, Durham, NC 

The authors examined the effect of apolipoprotein E4 (APOE4), the most common genetic variant associated with late-onset Alzheimer’s disease (AD), on perioperative neurocognition.  Subjects included 140 patients ≥ 60 years scheduled for nonneurologic, noncardiac surgery under general anesthesia. Findings showed APOE4 carriers with significantly greater resting state-functional MRI (rs-fMRI) connectivity differences between the left posterior cingulate and left angular/supramarginal gyrus regions, and between the right entorhinal cortex and left inferior frontal lobe region before surgery. This connectivity pattern decreases more after surgery in APOE4 carriers when compared to noncarriers, resulting in a postoperative normalization of functional connectivity between these brain regions in APOE4 carriers.

“Anesthetic activation of GABA_A receptors in astrocytes triggers a persistent increase in cell-surface expression of α5GABA_A receptors in neurons via IL-1β in mice”

Arsene Pinguelo, PhD Student, University of Toronto, Toronto, Ontario  

Using cortical astrocytes and hippocampal neurons from fetal mice, investigators explored mechanisms that raise inhibitory tonic current, the surface expression, linked to postanesthetic cognitive deficits generated by the α5 subunit-containing GABA_A receptors (α5GABA_ARs) in mouse hippocampal neurons. Findings showed anesthetic activation of GABA_ARs in astrocytes triggered the release of IL-1β from astrocytes. The release of IL-1β acts on neurons through phosphorylation of P38 MAPK, driving an increase in α5GABA_AR surface expression and function. There is novel cross talk between astrocytic and neuronal GABA_ARs — these may be targets that reduce postanesthesia cognitive deficits.

To find out more about their research, view ePosters at https://epostersonline.com/am2021.