E. J. Kovacs

University of Colorado | UCD · Department of Surgery, Division of GI, Tumor and Endocrine Surgery

Cutaneous burn injury in the elderly is associated with poor clinical outcomes and increased pulmonary-related complications. We and others have shown that burn injury triggers a cascade of inflammatory mediators which increase gut permeability and dysbiosis of the fecal microbiota and this is more dramatic in the aged. Since cross-talk between int...

Binge alcohol use is increasing among aged adults (>65 years). Alcohol-related toxicity in aged adults is associated with neurodegeneration, yet the molecular underpinnings of age-related sensitivity to alcohol are not well described. Studies utilizing rodent models of neurodegenerative disease reveal heightened activation of Nuclear factor kappa-l...

The Earth’s population is aging and, by 2050, 1 out of 6 people will be 65 or older. Therefore, proper treatment of injuries that disproportionately impact people of advanced age will be more important. Clinical studies reveal people aged ≥65 account for 16.5% of all burn injuries, and experience higher morbidity, including neurocognitive decline,...

Burn injuries are associated with significant morbidity and mortality, and lungs are the most common organ to fail. Interestingly, patients with alcohol intoxication at the time of burn have worse clinical outcomes, including pulmonary complications. Using a clinically relevant murine model, we have previously reported that episodic ethanol exposur...

Burn induces a systemic response affecting multiple organs, including the liver. Since the liver plays a critical role in metabolic, inflammatory, and immune events, a patient with impaired liver often exhibits poor outcomes. The mortality rate after burns in the elderly population is higher than in any other age group, and studies show that the li...

Introduction: Older adult burn victims have poorer outcomes than younger burn victims. The liver is critical for the recovery of patients with burns. Postburn hepatic apoptosis in young individuals compromises liver integrity; however, this pathway has not yet been studied in older individuals. Because aged animals with burns suffer significant li...

Introduction Liver damage following burn injury is associated with a poor prognosis. Thus, prevention, and early identification, of burn-induced liver damage will improve the outcomes of burn patients. Aspartate-aminotransferase (AST) and alanine-aminotransferase (ALT) help detect liver injury in extensive burns >50% of Total body surface area (TBS...

Prior research has focused on host factors as mediators of exaggerated sepsis-associated morbidity and mortality in older adults. This focus on the host, however, has failed to identify therapies that improve sepsis outcomes in the elderly. We hypothesized that the increased susceptibility of the aging population to sepsis is not only a function of...

On October 26th, 2022 the annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held as a satellite symposium at the annual meeting of the Society for Leukocyte Biology in Hawai'i. The 2022 meeting focused broadly on the immunological consequences of acute, chronic and prenatal alcohol exposure and how these contribute to damage...

Burn injured patients with alcohol use disorder (AUD) have increased morbidity and mortality compared to alcohol abstaining individuals with similar injuries. It is hypothesized that this is due, in part, to alcohol-induced dysregulation of the systemic inflammatory response, leading to worsened clinical outcomes, including increased susceptibility...

Burns are a leading cause of morbidity and mortality worldwide, affecting individuals of all ages. Burns induce a systemic response affecting multiple organs where the liver is frequently damaged. Since the liver plays a critical role in metabolic, inflammatory, and immune events, a patient with impaired liver often exhibits poor outcomes. The mort...

Alcohol misuse contributes to the dysregulation of immune responses and multiorgan dysfunction across various tissues, which are associated with higher risk of morbidity and mortality in people with alcohol use disorders. Organ‐specific immune cells, including microglia in the brain, alveolar macrophages in the lungs, and Kupffer cells in the liver...

Background By 2050, one in six people globally will be 65 or older. Confusion and delirium are significant complications after burn injury, especially in the elderly population. The etiology is still unknown, however complications may be driven by pro-inflammatory activation of astrocytes within the hippocampus (HPC) after burn injury. Reduced leve...

Alveolar macrophages (AMs) are tissue-resident cells of the lower airways that perform many homeostatic functions critical for pulmonary health and protection against pathogens. However, little is known about the factors that shape AMs during healthy aging. In these studies, we sought to characterize age-related changes in AM phenotype, function, a...

Alcohol use among older adults is on the rise. This increase is clinically relevant as older adults are at risk for increased morbidity and mortality from many alcohol-related chronic diseases compared to younger patients. However, little is known regarding the synergistic effects of alcohol and age. There is intriguing data suggesting that aging m...

Advanced age escalates post-burn complications and older burn patients, and even those with relatively minor burns, have worse clinical outcomes after injury. While the mechanism(s) responsible for the compounding effects of age and burn injury have not been defined, in this viewpoint, we highlight the emerging data suggesting that age-mediated imp...

On November 19th, 2021, the annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held at Loyola University Chicago Health Sciences Campus in Maywood, Illinois. The 2021 meeting focused on how alcohol misuse is linked to immune system derangements, leading to tissue and organ damage, and how this research can be translated into...

Alcohol consumption is commonplace in the United States and its prevalence has increased in recent years. Excessive alcohol use is linked to an increased risk of infections including pneumococcal pneumonia, mostly commonly caused by Streptococcus pneumoniae. In addition, pneumonia patients with prior alcohol use often require more intensive treatme...

By 2050, 1 in 6 people will be 65 or older. As the aging population grows so too does the importance of understanding how injuries in this age group lead to a greater incidence of neurological complications and mortality. Neurological complications may be driven by elevated pro-inflammatory cytokines and astrocyte activation within the hippocampus...

The portion of the global population that is over the age of 65 is growing rapidly and this presents a number of clinical complications, as the aged population is at higher risk for various diseases, including infection. For example, advanced age is a risk factor for heightened morbidity and mortality following infection with Streptococcus pneumoni...

Clinical studies have demonstrated that age ≥ 50 years old is an independent risk factor associated with poor prognosis after burn injury, the second leading cause of traumatic injuries in the aged population. While mechanisms driving age-dependent post-burn mortality are perplexing, changes in the intestinal microbiome however may contribute to th...

Background Advanced age is an independent risk factor for morbidity and mortality after burn injury. Following burn, the intestines can become permeable leading to the leakage of bacteria and their products from the lumen of the ileum to the portal and systemic circulation. Here, we sought to determine the effects of advanced age on intestinal perm...

Background There are currently > 600 million people over the age of 65 globally and this number is expected to double by the year 2050. Alcohol use among this population is on the rise, which is concerning as aging is associated with increased risk for a number of chronic illnesses. As most studies investigating the effects of alcohol have focused...

Alcohol use decreases host immune defense and increases susceptibility to pathogens such as Streptococcus pneumoniae. NOD2 is an intracellular pattern recognition receptor that binds muramyl dipeptide (MDP), a cell wall component of S. pneumoniae, and activates NF-kB signaling. To limit inflammation, NF-kB signaling is negatively regulated in part...

Objective: We aimed to examine biomarkers for screening unhealthy alcohol use in the trauma setting. Summary and background data: Self-report tools are the practice standard for screening unhealthy alcohol use; however, their collection suffers from recall bias and incomplete collection by staff. Methods: We performed a multi-center prospectiv...

Background: Elderly burn patients exhibit a lower survival rate compared with younger counterparts. The liver is susceptible to damage after burn injury, which predisposes to poor outcomes. Lipid homeostasis and the antioxidant glutathione system play fundamental roles in preserving liver integrity. Herein, we explored changes in these major pathw...

Abstract Objective Over the past decade, cannabis use has become increasingly popular in states that include Colorado. During this time, alcohol use disorders (AUDs) and alcohol-related medical conditions have also been consistently recognized as public health problems with increasing prevalence in the state. Despite the widespread use of cannabis...

The gastrointestinal (GI) tract is a vitally important site for the adsorption of nutrients as well as the education of immune cells. Homeostasis of the gut is maintained by the interplay of the intestinal epithelium, immune cells, luminal Ags, and the intestinal microbiota. The well‐being of the gut is intrinsically linked to the overall health of...

Background: Burn injury still has a high attributable mortality. The elevated mortality rate of severe burns is still concerning. Hepatic inflammation and injury are common after burns and are associated with poor outcomes. Necroptosis is a programmed cell death linked with inflammation. Thus, assessing necroptotic pathways in the liver can lead t...

On November 15, 2019, the 24th annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held as a satellite conference during the annual Society for Leukocyte Biology meeting in Boston, MA. The 2019 meeting focused on alcohol, immunity and organ damage and included two plenary sessions. The first session highlighted new research ex...

Introduction In the literature, the incidence of alcohol and/or drug use among burn patients ranges from 16.4%-69%. Burn patients with positive toxicology (tox) screens on admission are known to have increased rates of morbidity and mortality. To date little has been published on the effects of positive alcohol and/or drug screens on outcomes in th...

Introduction E-cigarettes and vaporizers (E-cigs) have seen a dramatic surge in popularity. The Centers for Disease Control now estimates that 1 in 4 United States (US) high school students use E-cigs. Recent recognition of E-cig-related lung injury has garnered significant attention. However, relatively little is known about E-cig-related burn inj...

Introduction Alcohol has been shown to increase hospital length of stay, complications and mortality in burn patients in studies examining its effects over the past 25 years. In contrast, there is a scarcity of published data on the effects of marijuana and other drugs of abuse in the burn population. The primary aim of this study is to evaluate th...

On August 27 and 28, 2018, the American Burn Association, in conjunction with Underwriters Laboratories, convened a group of experts on burn and inhalation injury in Washington, DC. The goal of the meeting was to identify and discuss the existing knowledge, data, and modeling gaps related to understanding cutaneous thermal injury and inhalation inj...

Introduction: Excessive alcohol use (EAU), a harmful pattern of drinking that includes binge drinking and heavy use, occurs in 25% (binge) and 6% (heavy use) of the US population, respectively. Little is known about alcohol use in individuals with cystic fibrosis (CF). The objective of this investigation is to examine alcohol consumption patterns...

Gastrointestinal hormones are essential in postburn metabolism. Since near 50% of burn victims test positive for blood-alcohol-levels at hospital admission and have inferior outcomes compared to non-intoxicated burn-patients; we hypothesized that the gastrointestinal hormone secretion is compromised in intoxicated burn victims. To test our theory,...

Pulmonary and systemic insults from inhalation injury can complicate the care of burn patients and contribute to significant morbidity and mortality. However, recent progress in diagnosis and treatment of inhalation injury has not kept pace with the care of cutaneous thermal injury. There are many challenges unique to inhalation injury that have sl...

Objective This study examines health outcomes in burn patients with sepsis. We hypothesized that burn patients with sepsis would have an increased odds risk for in-hospital death and longer intensive care unit (ICU) stays. Methods This was a retrospective cohort of consecutive patients admitted to the burn ICU with total burn surface area (TBSA) ≥...

Maintenance of the commensal bacteria that comprise the gut microbiome is essential to both gut and systemic health. Traumatic injury, such as burn, elicits a number of changes in the gut, including a shift in the composition of the microbiome (dysbiosis), increased gut leakiness, and bacterial translocation into the lymphatic system and bloodstrea...

The relatively low long-term survival rate of lung transplant recipients as compared to other organ recipients serves as an impetus to identify potential lung dysfunction as early as possible. There is an association between donor heavy alcohol use and acute lung injury in the lung allograft after transplant, known as primary graft dysfunction. Exc...

Cutaneous burn injury is one of the most devastating injuries one can obtain with tissue damage extending beyond the skin wound to distal organs, including the gastrointestinal tract, liver, and lungs. Multiple organ failure is a leading cause of death after burn injury resulting in excessive systemic and localized inflammation directly contributin...

On January 26, 2018, the 23rd annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held at the University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado. The meeting consisted of plenary sessions with oral presentations and a poster presentation session. There were four plenary sessions that covered a wide range...

In the letter by Nguyen et al. 2018, the authors raise several concerns in measuring PEth in critically ill patients, most notably that our calculated cut‐points are higher than previously described that may in part be attributable to lower red cell volume in critically ill patients. We appreciate their comments and acknowledge substantial variabil...

Burn patients who consumed alcohol prior to injury have worse clinical outcomes, including longer hospital stays, increased ventilator days, and more respiratory infections. Most alcohol consumers are binge drinkers and not chronic alcoholics and binge drinking patterns fluctuate over the week, with consecutive days of drinking over the weekend fol...

Introduction The elderly have an elevated basal inflammation state called “inflamm-aging”, which may render them less able to withstand burn injury. Under normal conditions, the host and gastrointestinal microbiota have a symbiotic relationship that maintain immune defense, mucosal barrier integrity, and nutritional status. When intact, intestinal...

Introduction The systemic inflammatory response seen after burns and other forms of traumatic injury is accompanied by production of antimicrobial peptides such as calprotectin (S100A8/A9) and an expansion of granulocytic Gr-1⁺CD11b⁺ myeloid cells. Research in the fields of burns, sepsis, and trauma have established that these cells can exhibit an...

Little is known about the alcohol habits of people with advanced lung disease. Following lung transplantation patients are asked to abstain from or minimize alcohol use. The aim of this investigation is to assess alcohol use in a cohort of patients with advanced lung disease undergoing evaluation for lung transplant. This is a prospective observati...

Objective: To derive and validate a prediction model for the development of ARDS in burn-injured patients. Summary background data: Burn injury carries the highest incidence of acute respiratory distress syndrome (ARDS) among all predisposing conditions, but few studies exist on risk factors in these patients. Studies employing biomarkers and cl...

Phosphatidylethanol is a direct alcohol biomarker for identifying alcohol misuse. It carries several advantages over other alcohol biomarkers, including a detection half-life of several weeks and little confounding by patient characteristics or organ dysfunction. The aim of this study is to derive an optimal phosphatidylethanol cut point to identif...

This prospective study aimed to address changes in inflammatory response between different aged populations of patients who sustained burn and inhalation injury. Plasma and bronchoalveolar lavage (BAL) samples were collected from 104 patients within 15h of their estimated time of burn injury. Clinical variables, laboratory parameters, and immune me...

On June 24, 2017, the 22nd annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held as a satellite conference during the annual Research Society on Alcoholism (RSA) Scientific Meeting in Denver, CO. The 2017 meeting focused broadly on mechanisms that link alcohol to tissue injury and inflammation, and how this research can be...

Background: This study aims to determine the relationship between tobacco use, inhalation injury, and ARDS in burn-injured adults. Methods: This study was an observational cohort of 2,485 primary burn admissions to a referral burn center between January 1, 2008 and March 15, 2015. Subjects were evaluated by methods used to account for mediation...

Background: Although alcohol misuse is associated with deleterious outcomes in critically ill patients, its detection by either self-report or examination of biomarkers is difficult to obtain consistently. Phosphatidylethanol (PEth) is a direct alcohol biomarker that can characterize alcohol consumption patterns; however, its diagnostic accuracy i...

With the coming of the "silver tsunami," expanding the knowledge about how various intrinsic and extrinsic factors affect the immune system in the elderly is timely and of immediate clinical need. The global population is increasing in age. By the year 2030, more than 20% of the population of the United States will be older than 65 years of age. Th...

The global population is aging: in 2010, 8% of the population was older than 65 y, and that is expected to double to 16% by 2050. With advanced age comes a heightened prevalence of chronic diseases. Moreover, elderly humans fair worse after acute diseases, namely infection, leading to higher rates of infection-mediated mortality. Advanced age alter...

Death from chronic lung disease is increasing and Chronic Obstructive Pulmonary Disease has become the third leading cause of death in the United States in the past decade. Both chronic and acute lung diseases disproportionately affect elderly individuals, making it likely that these diseases will become more frequent and severe as the worldwide po...

To develop an algorithm to identify sepsis and sepsis with organ dysfunction/septic shock in burn-injured patients incorporating criteria from the American Burn Association sepsis definition that possesses good test characteristics compared with International Classification of Diseases, Ninth Revision-Clinical Modification (ICD-9) codes and an algo...

Asthma in the elderly (.65 yr old) is common and associated with higher morbidity and mortality than asthma in younger patients. The poor outcomes in this group are due, in part, to underdiagnosis and undertreatment.There are a varietyof factors related toagingitself that affect the presentation of asthma in the elderly and influence diagnosis and...

The world is undergoing an unprecedented shift in demographics, with the number of individuals over the age of 60 projected to reach 2 billion or more by 2050, representing 22% of the global population. The elderly are at a higher risk for chronic disease and more susceptible to infection, due in part to age-related dysfunction of the immune system...

Dendritic cells (DCs) are a critical component of anti-tumor immunity due to their ability to induce a robust immune response to antigen (Ag). Alcohol was previously shown to reduce DC ability to present foreign Ag and promote pro-inflammatory responses in situations of infection and trauma. However the impact of alcohol exposure on generation of a...

Annually, excessive alcohol use accounts for more than $220 billion in economic costs and 80,000 deaths, making excessive alcohol use the third leading lifestyle-related cause of death in the US. Patients with an alcohol-use disorder (AUD) also have an increased susceptibility to respiratory pathogens and lung injury, including a 2–4-fold increased...

In this study, the role and fate of AMs were examined in pulmonary inflammation after intoxication and injury. Clinical evidence has revealed that half of all burn patients brought to the emergency department are intoxicated at the time of injury. This combined insult results in amplified neutrophil accumulation and pulmonary edema, with an increas...

On September 27, 2015 the 20th annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held as a satellite symposium at the annual meeting of the Society for Leukocyte Biology in Raleigh, NC. The 2015 meeting focused broadly on adverse effects of alcohol and alcohol-use disorders in multiple organ systems. Divided into two plenary...

Significance: With the growing population of baby boomers, there is a great need to determine the effects of advanced age on the function of the immune system. Recent Advances: It is universally accepted that advanced age is associated with a chronic low-grade inflammatory state referred to as inflamm-aging which alters the function of both immune...

Objectives: Clinical and animal studies demonstrate that alcohol intoxication at the time of injury worsens postburn outcome. The purpose of this study was to determine the role and mechanism of Kupffer cell derangement in exacerbating postburn end organ damage in alcohol-exposed mice. Design: Interventional study. Setting: Research Institute....

Females have a higher rate of mortality following burn injury, largely due to differences in sepsis-related mortality. The present study seeks to understand the underpinnings of the estrogen's immunomodulatory effects in a murine model of burn injury and infection. Gonad-intact and ovariectomized female mice were subjected to a 15% total BSA scald...

Background: Over a quarter of the US population qualify as excessive alcohol consumers. Alcohol use impacts several lung diseases and heavy consumption has been associated with poor clinical outcomes. The fractional excretion of exhaled nitric oxide (FeNO) has clinical implications in multiple airway diseases. We hypothesized that excessive alcoho...

Dermal burn injury causes profound physiological derangements. Respiratory failure is a primary cause of morbidity and mortality after burn injury, in part, because of excessive and prolonged release of local and systemic proinflammatory mediators. Clinical and preclinical evidence suggests histone deacetylases (HDACs) are key mediators of inflamma...

On November 21, 2014 the 19th annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held at Loyola University Chicago Health Sciences Campus in Maywood, Illinois. The meeting focused broadly on inflammatory cell signaling responses in the context of alcohol and alcohol-use disorders, and was divided into four plenary sessions fo...

Alcohol use disorders (AUDs) are associated with increased susceptibility to pulmonary diseases, including bacterial pneumonia and acute respiratory distress syndrome (ARDS). Alveolar macrophages (AMs) play a vital role in the clearance of pathogens and regulation of inflammation, but these functions may be impaired in the setting of alcohol exposu...

Clinical data indicate that cutaneous burn injuries covering greater than 10% of the total body surface area are associated with significant morbidity and mortality, in which pulmonary complications, including acute respiratory distress syndrome (ARDS), contribute to nearly half of all patient deaths. Approximately 50% of burn patients are intoxica...

The widespread and rapidly increasing trend of binge drinking is accompanied by a concomitant rise in the prevalence of trauma patients under the influence of alcohol at the time of their injury. Epidemiological evidence suggests up to half of all adult burn patients are intoxicated at the time of admission, and the presence of alcohol is an indepe...

A blood alcohol level above 0 g/dL is found in up to 50% of patients presenting with traumatic injuries. The presence of alcohol in the blood not only increases the risk of traumatic injury, but it is also associated with worse outcomes and trauma recidivism. In light of these risks, the American College of Surgeons Committee on Trauma advocates sc...

MΦ are multipurpose phagocytes with a large repertoire of well-characterized abilities and functions, including regulation of inflammation, wound healing, maintenance of tissue homeostasis, as well as serving as an integral component of the innate-immune defense against microbial pathogens. Working along with neutrophils and dendritic cells, the ot...

Objective: Herein, we tested the effects of high levels of supplemental estrogen treatment on cutaneous wound healing. Approach: Female mice were implanted with a 17β-estradiol (E2) secreting pellet or placebo before receiving a full-thickness dermal excisional wound. Mice receiving the E2 pellet attained hormone levels that are comparable to those...