Laquanda Knowlin

The measured effect magnitude of co-morbidities on burn injury mortality

INTRODUCTION The ability to better prognosticate burn injury outcome is challenging and historically, most center use the Baux or revised Baux score to help prognosticate burn outcome, however, the weighted contribution of comorbidity on burn mortality has traditionally not been accounted for nor adequately studied. We therefore sought to determine the effect of comorbidities, using the Charlson comorbidity index (CCI) on burn mortality. METHODS The purpose of this study was to determine the effect of comorbidities on burn injury mortality as determined by the LA50 (lethal TBSA burn at which 50% of the cohort will succumb from the burn injury) in a retrospective analysis of patients admitted to a regional burn center from 2002 to 2012. Independent variables analyzed included basic demographics, burn mechanism, presence of inhalation injury, TBSA (total body surface area), length of hospital stay, and pre-existing comorbidities. Bivariate analysis was performed and logistic regression modeling using significant variables was utilized to estimate odds of death. RESULTS 7640 patients were included in this study. Overall survival rate was 96%. 40% of our burn cohort had at least one comorbidity. There was a linear increase in the likelihood of death with an increase in CCI. The logistic regression model for mortality outcomes identified four statistically significant variables: age, TBSA, inhalational injury and the presence of comorbidities (OR=1.59 for each 1 point increase in CCI; 95% CI 1.44-1.77). The unadjusted LA50 was 53% for the entire cohort. Partial adjustment multivariate regression controlling for burn mechanism and inhalation injury only, produced a slight reduction in LA50 for the 0-18 and 19-64 age categories to 76% and 48% TBSA, respectively, but a significant decrease occurred in the ≥65 years age group with a reduced LA50 to 20% TBSA (p<0.001). After full adjustment for all significant covariates, including comorbidities, the independent magnitude of effect of comorbidities on the LA50 was evident in the <65 cohort. The full adjustment showed a LA50 decreased to 61% and 43% TBSA, respectively in the 0-18 and >18-65 age groups respectively (p<0.001), however, in the >65 years age cohort there was no change in the LA50. CONCLUSION Preexisting comorbidities have a significant effect on burn injury mortality in all age groups, particularly the younger burn population. The measured effect of comorbidities in the >65 yr age cohort was mitigated by the co-linearity between age and comorbidities. The inclusion of CCI is imperative so as to better prognosticate burn outcome and help guide expectations and resource utilization, particularly in the younger burn cohort.

Differential regulation of innate immune cytokine production through pharmacological activation of Nuclear Factor-Erythroid-2-Related Factor 2 (NRF2) in burn patient immune cells and monocytes

Burn patients suffer from immunological dysfunction for which there are currently no successful interventions. Similar to previous observations, we find that burn shock patients (≥15% Total Burn Surface Area (TBSA) injury) have elevated levels of the innate immune cytokines Interleukin-6 (IL-6) and Monocyte Chemoattractant Protein-1 (MCP-1)/CC-motif Chemokine Ligand 2(CCL2) early after hospital admission (0–48 Hours Post-hospital Admission (HPA). Functional immune assays with patient Peripheral Blood Mononuclear Cells (PBMCs) revealed that burn shock patients (≥15% TBSA) produced elevated levels of MCP-1/CCL2 after innate immune stimulation ex vivo relative to mild burn patients. Interestingly, treatment of patient PBMCs with the Nuclear Factor-Erythroid-2-Related Factor 2 (NRF2) agonist, CDDO-Me(bardoxolone methyl), reduced MCP-1 production but not IL-6 or Interleukin-10 (IL-10) secretion. In enriched monocytes from healthy donors, CDDO-Me(bardoxolone methyl) also reduced LPS-induced MCP1/CCL2 production but did not alter IL-6 or IL-10 secretion. Similar immunomodulatory effects were observed with Compound 7, which activates the NRF2 pathway through a different and non-covalent Mechanism Of Action (MOA). Hence, our findings with CDDO-Me(bardoxolone methyl) and Compound 7 are likely to reflect a generalizable aspect of NRF2 activation. These observed effects were not specific to LPS-induced immune responses, as NRF2 activation also reduced MCP-1/CCL2 production after stimulation with IL-6. Pharmacological NRF2 activation reduced Mcp-1/Ccl2 transcript accumulation without inhibiting either Il-6 or Il-10 transcript levels. Hence, we describe a novel aspect of NRF2 activation that may contribute to the beneficial effects of NRF2 agonists during disease. Our work also demonstrates that the NRF2 pathway is retained and can be modulated to regulate important immunomodulatory functions in burn patient immune cells.

Burn mortality in patients with preexisting cardiovascular disease

INTRODUCTION Burn shock, a complex process, which develops following burn leads to severe and unique derangement of cardiovascular function. Patients with preexisting comorbidities such as cardiovascular diseases may be more susceptible. We therefore sought to examine the impact of preexisting cardiovascular disease on burn outcomes. METHODS A retrospective analysis of patients admitted to a regional burn center from 2002 to 2012. Independent variables analyzed included basic demographics, burn mechanism, presence of inhalation injury, TBSA, pre-existing comorbidities, and length of ICU/hospital stay. Bivariate analysis was performed and Poisson regression modeling was utilized to estimate the incidence of being in the ICU and mortality. RESULTS There were a total of 5332 adult patients admitted over the study period. 6% (n=428) had a preexisting cardiovascular disease. Cardiovascular disease patients had a higher mortality rate (16%) compared to those without cardiovascular disease (3%, p<0.001). The adjusted Poisson regression model to estimate incidence risk of being in intensive care unit in patients with cardiovascular disease was 33% higher compared to those without cardiovascular disease (IRR=1.33, 95% CI=1.22-1.47). The risk for mortality is 42% higher (IRR=1.42, 95% CI=1.10-1.84) for patients with pre-existing cardiovascular disease compared to those without cardiovascular disease after controlling for other covariates. CONCLUSION Preexisting cardiovascular disease significantly increases the risk of intensive care unit admission and mortality in burn patients. Given the increasing number of Americans with cardiovascular diseases, there will likely be a greater number of individuals at risk for worse outcomes following burn. This knowledge can help with burn prognostication.

Burn injury mortality in patients with preexisting and new onset renal disease

INTRODUCTION We sought to examine the impact of preexisting and new onset renal disease on burn injury mortality. METHODS Retrospective analysis of patients admitted to a regional burn center from 2002-2012 was performed. Variables analyzed included demographics, burn mechanism, inhalation injury status, and % TBSA. Poisson regression was performed to estimate risk of in-hospital burn mortality. RESULTS There were a total of 7640 patients over the study period. The adjusted 60-day risk of in-hospital mortality in patients with preexisting renal disease (PRD was 3 times higher compared to patients with no preexisting renal disease (IRR = 3.22, 95% CI = 1.26-8.25). The adjusted 60-day risk of mortality is 2 times higher for patients with new onset renal disease compared to those without (IRR = 2.11, 95% CI = 1.55-2.87). CONCLUSION Preexisting and new onset renal disease results in a significantly higher risk of mortality following burn injury compared to patients without renal disease. Prevention of new onset renal injury and careful management of patients with preexisting renal disease to prevent exacerbation should be pursued.

Correction: Differential regulation of innate immune cytokine production through pharmacological activation of Nuclear Factor-Erythroid-2-Related Factor 2 (NRF2) in burn patient immune cells and monocytes (PLoS ONE (2017) 12:9 (e0184164) DOI: 10.1371/journal.pone.0184164)

[This corrects the article DOI: 10.1371/journal.pone.0184164.].

The effect of smoking status on burn inhalation injury mortality

INTRODUCTION Three factors that effect burn mortality are age, total body surface of burn (TBSA), and inhalation injury. Of the three, inhalation injury is the strongest predictor of mortality thus its inclusion in the revised Baux score (age+TBSA+17* (inhalation injury, 1=yes, 0=no)). However, the weighted contribution of specific comorbidities such as smoker status on mortality has traditionally not been accounted for nor studied in this subset of burn patients. We therefore sought to examine the impact of current tobacco and/or marijuana smoking in patients with inhalation injury. METHODS A retrospective analysis of patients admitted to a regional burn center from 2002 to 2012. Independent variables analyzed included basic demographics, burn mechanism, presence of inhalation injury, TBSA, pre-existing comorbidities, and smoker status. Bivariate analysis was performed and logistic regression modeling using significant variables was utilized to estimate odds of mortality. RESULTS There were a total of 7640 patients over the study period. 7% (n=580) of the burn cohort with inhalation injury were included in this study. In-hospital burn mortality for inhalation injury patients was 23%. Current smokers (20%) included cigarette smokers and marijuana users, 19% and 3%, respectively. Preexisting respiratory disease (17%) was present in 36% of smokers compared to 13% of non-smokers (p<0.001). Smokers had significantly lower mortality rate (9%) compared to non-smokers (26%, p<0.01). The logistic regression model for mortality outcomes identified statistically four significant variables: age, TBSA, ethnicity, and smoker status (OR=0.41, 95% CI=0.18-0.93). Presence of comorbidities, including preexisting respiratory disease, was not significant. CONCLUSION In the sub group of burn patients with inhalation injury, the odds of mortality significantly decreased in pre-existing smokers after adjusting for significant covariates. We postulate that an immune tolerance mechanism that modulates and diminishes the pro-inflammatory response confers a survival advantage in smokers after exposure to acute smoke inhalation injury. Future prospective studies in human and/or animal models are needed to confirm these findings.

The effect of preexisting respiratory co-morbidities on burn outcomes ☆

INTRODUCTION Burns cause physiologic changes in multiple organ systems in the body. Burn mortality is usually attributable to pulmonary complications, which can occur in up to 41% of patients admitted to the hospital after burn. Patients with preexisting comorbidities such as chronic lung diseases may be more susceptible. We therefore sought to examine the impact of preexisting respiratory disease on burn outcomes. METHODS A retrospective analysis of patients admitted to a regional burn center from 2002-2012. Independent variables analyzed included basic demographics, burn mechanism, presence of inhalation injury, TBSA, pre-existing comorbidities, smoker status, length of hospital stay, and days of mechanical ventilation. Bivariate analysis was performed and Cox regression modeling using significant variables was utilized to estimate hazard of progression to mechanical ventilation and mortality. RESULTS There were a total of 7640 patients over the study period. Overall survival rate was 96%. 8% (n=672) had a preexisting respiratory disease. Chronic lung disease patients had a higher mortality rate (7%) compared to those without lung disease (4%, p<0.01). The adjusted Cox regression model to estimate the hazard of progression to mechanical ventilation in patients with respiratory disease was 21% higher compared to those without respiratory disease (HR=1.21, 95% CI=1.01-1.44). The hazard of progression to mortality is 56% higher (HR=1.56, 95% CI=1.10-2.19) for patients with pre-existing respiratory disease compared to those without respiratory disease after controlling for patient demographics and injury characteristics. CONCLUSION Preexisting chronic respiratory disease significantly increases the hazard of progression to mechanical ventilation and mortality in patients following burn. Given the increasing number of Americans with chronic respiratory diseases, there will likely be a greater number of individuals at risk for worse outcomes following burn.

Burn injury outcomes in patients with pre-existing diabetic mellitus: Risk of hospital-acquired infections and inpatient mortality ☆

BACKGROUND Diabetes mellitus (DM) is a major cause of illness and death in the United States, and diabetic patients are at increased risk for burn injury. We therefore sought to examine the impact of pre-existing DM on the risk of inpatient mortality and hospital acquired infections (HAI) among burn patients. METHODS Adult patients (≥18 years old) admitted from 2004 to 2013 were analyzed. Weighted Kaplan-Meier survival curves - adjusting for patient demographics, burn mechanism, presence of inhalation injury, total body surface area, additional comorbidities, and differential lengths of stay - were used to estimate the 30-day and 60-day risk of mortality and HAIs. RESULTS A total of 5539 adult patients were admitted and included in this study during the study period. 655 (11.8%) had a pre-existing DM. The crude incidence of HAIs and in-hospital mortality for the whole burn cohort was 8.5% (n=378) and 4.4% (n=243), respectively. Diabetic patients were more likely to be older, female, have additional comorbidities, inhalational injury, and contact burns. After adjusting for patient and burn characteristics, the 60-day risk of HAI among patients with DM was significantly higher, compared to non-diabetic patients (RR 2.07, 95% CI 1.28, 6.79). However, no significant difference was seen in the 60-day risk of mortality (RR 1.34, 95% CI 0.44, 3.10). CONCLUSIONS Pre-existing DM significantly increases the risk of developing an HAI in patients following burn injury, but does not significantly impact the risk of inpatient mortality. Further understanding of the immune modulatory mechanism of burn injury and DM is imperative to better attenuate the acquisition of HAIs.

1502: THE EFFECT OF PREEXISTING RESPIRATORY COMORBIDITIES ON BURN INJURY OUTCOMES

Learning Objectives: Burn injuries cause physiologic changes in multiple organ systems in the body. Following major burns, mortality is usually attributable to pulmonary complications, which can occur in up to 41% of patients admitted to the hospital after burn injury. Patients with preexisting comorbidities such as chronic lung diseases may be more susceptible. We therefore sought to examine the impact of preexisting respiratory disease on burn injury outcomes. Methods:A retrospective analysis of patients admitted to a regional burn center from 2002–2012. Independent variables analyzed included basic demographics, burn mechanism, presence of inhalation injury, total body surface area (TBSA) of burn, pre-existing comorbidities, smoker status, length of hospital stay, and days of mechanical ventilation. Bivariate analysis was performed and Cox regression modeling using significant variables was utilized to estimate hazard of progression to mechanical ventilation and mortality. Results: There were a total of 7640 patients over the study period. Overall survival rate was 96%. 8% (n=672) had a preexisting respiratory disease. Chronic lung disease patients had a higher crude mortality rate (7%) compared to those without lung disease (4%, p <0.01). The adjusted Cox regression model to estimate the hazard of progression to mechanical ventilation in patients with respiratory disease was 21% higher compared to those without respiratory disease (HR =1.21, 95% CI = 1.01–1.44). The hazard of progression to mortality is 56% higher (HR = 1.56, 95% CI = 1.10–2.19) for patients with pre-existing respiratory disease compared to those without respiratory disease after controlling for patient demographics and injury characteristics. Conclusions: Preexisting respiratory disease significantly increases the hazard of progression to mechanical ventilation and mortality in patients following burn injury.Given the increasing number of Americans with acute or chronic respiratory diseases, there will likely be a greater number of individuals at risk for worse outcomes following burn injury.