Immune response profiling in patients with traumatic injuries associated with alcohol ingestion.

Abstract

Traumatic injuries afflict more than 5 million people globally every year. Current and past animal research has demonstrated association among alcohol, trauma, and impaired immune function, whereas human registries have shown association between alcohol and morbidity as well as mortality. The purpose of this study is to elucidate the immune interactions with alcohol in traumatically injured patients. We prospectively enrolled 379 patients after trauma at three medical centers in the Surgical Critical Care Initiative. Plasma was analyzed using Luminex for up to 35 different cytokines. Collected samples were grouped by patients with detectable plasma alcohol levels versus those without. Univariate testing determined differences in analytes between groups. We built Bayesian belief networks with multiple minimum descriptive lengths to compare the two groups. All 379 patient samples were analyzed. Two hundred eighty-two (74.4%) patients were men, and 143 (37.7%) were White. Patients had a median intensive care unit length of stay (LOS) of 5.8 days and hospital LOS of 12 days. Using single variate analyses, eight different cytokines were differentially associated with alcohol. Cytokines IL-12 and IL-6 were important nodes in both models and IL-10 was a prominent node in the nonalcohol model. This study found select immune function differed between traumatically injured patients with measurable serum alcohol levels as compared with those without. Traumatically injured patients with positive blood alcohol content appear less able to inhibit inflammatory stress. Alcohol appears to suppress pro-inflammatory IL-12 and IL-6, whereas patients without alcohol have greater levels of anti-inflammatory IL-10 expressed at injury and may better regulate anti-inflammatory pathways. Future studies should determine the relationship with these markers with clinically oriented outcomes.

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Citation

Published Version (Please cite this version)

10.1111/cts.13022

Publication Info

Breslin, Adam W, Alexander T Limkakeng, Elizabeth Silvius, Catherine A Staton, Chandra Almond, Mary-Beth Joshi, Bartley Adams, Bria Johnston, et al. (2021). Immune response profiling in patients with traumatic injuries associated with alcohol ingestion. Clinical and translational science, 14(5). pp. 1791–1798. 10.1111/cts.13022 Retrieved from https://hdl.handle.net/10161/24041.

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Scholars@Duke

Limkakeng

Alexander Tan Limkakeng

Professor of Emergency Medicine

Dr. Alexander T. Limkakeng, Jr., MD, MHSc, FACEP is a Professor of Emergency Medicine, Vice Chair of Clinical Research, Director of the Acute Care Research Team, and Director of the Resident Research Fellowship for the Department of Emergency Medicine in the Duke University School of Medicine in Durham, North Carolina.

Dr. Limkakeng has served as chair of the American College of Emergency Physicians (ACEP) Research Committee, and been the Course Director of the ACEP Research Forum from 2016-2018, the largest emergency medical research platform in the nation. He is also the Assistant Director of ACEP’s Emergency Medicine Basic Research Skills course. He was elected to the Nominating Committee of the Society of Academic Emergency Medicine.

As a researcher, Dr. Limkakeng has led multiple clinical trials and interdepartmental sponsored projects and is author on over 100 peer-reviewed manuscripts. These include studies in emergency conditions such as COVID-19, traumatic brain injury, hypertension, heart failure, thrombosis, stroke, envenomations, and septic shock. His research has been funded by grants and contracts totaling over $9 million dollars. He has lectured internationally on acute coronary syndrome, responsible conduct of research, design of clinical trials, and precision medicine in emergency care. He has led Duke’s involvement in NIH-funded research networks and in industry-funded work that led to FDA approval for multiple high-sensitivity cardiac troponin assays and point-of-care COVID-19 diagnostic tests. He has servesd as Co-PI for the Duke U24 Hub in the NIH Early Phase Pain Investigation Clinical Network (EPPIC-Net) (1U24NS114416) and now serves as a co-PI on the Duke U24 Hub award (1U24NS129498) in the NIH Strategies to Innovate Emergency Care Clinical Trials (SIREN) Network and in the NIH NINDS Strokenet network (1U24NS135250)

His personal research interest is finding new ways to diagnose acute coronary syndrome. In particular, he is interested in novel biomarkers and precision medicine approaches to this problem. The common element throughout this work is a focus on time-sensitive health conditions.
Staton

Catherine Ann Staton

Professor of Emergency Medicine

Catherine Staton MD MSc

Dr. Staton is an Associate Professor in Emergency Medicine (EM), Neurosurgery & Global Health with tenure at Duke University. She is the Director of the GEMINI (Global EM Innovation & Implementation) Research Center and the EM Vice Chair of Research Strategy & Faculty Development. Her research integrates innovative implementation methods into health systems globally to improve access to acute care. In 2012, with an injury registry at Kilimanjaro Christian Medical Center, Tanzania Dr. Staton demonstrated 30% of injury patients had at risk alcohol use, providing preliminary data for a K01/Career Development Award. Her K01 award adapted a brief alcohol intervention to the KCMC ED and Swahili and is now being trialed in an NIAAA funded R01 pragmatic adaptive clinical trial. Dr. Staton and her mentor and collaborator Dr. Mmbaga are co-PD of the “The TReCK Program: Trauma Research Capacity Building in Kilimanjaro” to train 12 masters and doctoral learners to conduct innovative implementation and data science projects to improve care for injury patients. Currently, Dr. Staton and GEMINI partners with over a dozen faculty from over 6 low- and middle-income countries to conduct research, has mentored over 150 learners from undergraduate to post-doctoral levels from high, middle and low- income settings and has over 130 manuscripts.

Kirk

Allan Douglas Kirk

David C. Sabiston, Jr. Distinguished Professor of Surgery

I am a surgeon with interest in immune management of transplant recipients. I am particularly interested in therapies that influence T cell costimulation pathways and adjuvant therapies that facilitate costimulation blockade to prevent the rejection of transplanted organs without undue suppression of protective immunity. I am also interested in understanding how injury, such as that occurring during trauma or in elective surgery, influences immune responses and subsequent healing following injury.


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