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Flare gun injuries are rare, and patients often present with complex trauma that may require multiple operative interventions. Our objective is to explore a case of a 15-year-old male, who presented with second-degree flame burns to the face, left upper extremity and bilateral hands, as well as third-degree burns to the oropharynx and a tongue laceration after a flare gun was discharged into his mouth. The patient underwent multiple debridements of the oral cavity and oropharynx, and his hospital course was complicated by an intra-oral abscess. He eventually made a full recovery and was discharged. This case not only illustrates the need for early operative intervention, but it also underscores the need for awareness campaigns that highlight the dangers of flare guns and similar devices., (© 2023 Euro-Mediterranean Council for Burns and Fire Disasters.)

Many burn survivors suffer from psychiatric sequelae long after their physical injuries have healed. This may even be more pronounced in individuals who have a history of mental health disorders prior to admission. The aim of this study was to explore the clinical outcomes of patients with previously diagnosed mental health disorders who were admitted to our Burn Center. This was a single-site, retrospective review using our institutional Burn Center registry. All adult patients (18 years or older) admitted to our Burn Center between January 1, 2014 and June 30, 2021 with burn injury or inhalation injury were included in this study. Variables of interest included demographics and burn mechanism. Outcomes of interests were length of stay, cost of hospitalization, and mortality. A P-value of < .05 was considered statistically significant for all analyses. There were 4958 patients included in this study, with 35% of these patients having a previous diagnosis of mental health disorders. Patients with mental health disorders were younger, with larger burns, P < .05. They had significantly longer lengths of stay and significantly higher costs (P < .00001). Mortality for those with a mental health disorder history was 2% and 3% for those without (P = .04). Patients with pre-existing mental health disorders had decreased odds of mortality. However, they do have extended lengths of stay, which may exhaust current sparse staff and burn bed resources., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The addition of trauma to burn injuries may result in higher morbidity and mortality. The purpose of this study was to evaluate the outcomes of pediatric patients with a combination of burn and trauma injuries, and included all pediatric Burn only, Trauma only, and combined Burn-Trauma patients admitted between 2011 and 2020. Mean length of stay, ICU length of stay, and ventilator days were highest for the Burn-Trauma group. The odds of mortality were almost 13 times higher for the Burn-Trauma group when compared to the Burn only group ( P = .1299). After using inverse probability of treatment weighting, the odds of mortality were almost 10 times higher for the Burn-Trauma group in comparison to the Burn only group ( P < .0066). Thus, the addition of trauma to burn injuries was associated with increased odds of mortality, as well as longer ICU and overall hospital length of stay in this patient population.

A history of malignancy is associated with worse outcomes in cardiac disease and trauma. Our objective was to determine if a past medical history or comorbid condition of cancer portends an increased morbidity or mortality in burns or skin-sloughing disorders at our institution. Patients were identified using our Institutional Burn Center registry and linked to the clinical and administrative data. All patients admitted between January 1, 2014 and June 30, 2021 were eligible for inclusion. Demographics, length of stay, comorbid conditions and mortality were evaluated. Statistical analysis was performed with Kruskal-Wallis, chi-square, and Fisher's exact tests. Seven thousand three hundred seventy-two patients were admitted during this time period. Three hundred eighty-six patients had a history of cancer (5%). Patients with a history of cancer were older (56 vs 44 years, P < .0001). They had a significantly longer length of stay (16 vs 10 days, P < .0001). They also had larger burns and higher hospital costs ($147,021 versus $83,788, P < .0001), were more likely to be male and more likely to have a skin-sloughing disorder. A history of cancer was not associated with increased odds of burn mortality. Thus, a history of cancer is associated with increased lengths of stay and costs in patients admitted for burn injury or skin-sloughing disorders, but not associated with increased mortality. Further study is warranted to investigate and mitigate what aspects of their care could be adjusted to improve outcomes., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The presence of any comorbid condition may lead to worse outcomes after burn injury. Chronic obstructive pulmonary disease (COPD) is a condition with significant morbidity and mortality. In 2018, about 16 million adults in the United States reported a diagnosis of COPD based on data from the American Lung Association. The objective of this study was to explore the outcomes of patients with COPD admitted to our Burn Center with flame burns and/or inhalation injury. Patients were identified using our Institutional Burn Center registry and linked to the clinical and administrative data. All adult flame-injured and/or inhalation injury-only patients admitted to our burn center between July 1, 2011 and June 30, 2020 were included. Demographics, length of stay, burn, and patient characteristics and outcomes, including mortality, were evaluated. Four thousand three hundred ninety-seven patients were included in the study. Patients were divided into two populations, those with COPD (n = 515) and those without a diagnosis of COPD (n = 3882). Patients with COPD were older, more likely to be white and male, and had smaller sized burns, p < .001. Patients with COPD were more likely to be smokers and have comorbid conditions. There was no statistically significant difference between the incidence of inhalation injury, lengths of stay, or number of ventilator days. Burn size and inhalation injury increased mortality risk regardless of COPD severity, as did age among those not on home oxygen. More studies are needed to determine the genomic or proteomic changes in patients with COPD that lead to worse outcomes after flame injury, and/or inhalation injury alone., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are conditions characterized by an immune-mediated skin reaction that results in blistering and epidermal detachment. Most cases are caused by drug hypersensitivity; however, recently there have been many publications documenting the association between coronavirus disease 2019 (COVID-19) and SJS/TEN. Our objective is to explore a case of a 4-year-old female who presented with a papular rash on her thighs that progressively worsened and spread to her face, trunk, and genital area. The patient tested positive for COVID-19. She required treatment with intravenous immunoglobulin (IVIG) and IV methylprednisolone, but eventually made a full recovery. This case underscores the need for awareness of the wide spectrum of dermatologic presentations in COVID-19 patients., Competing Interests: None., (IJBT Copyright © 2022.)

Acute alcohol intoxication in burn patients has been associated with increased mortality, renal dysfunction, and difficulty with adequate fluid resuscitation. It is less clear how chronic alcohol use, regardless of intoxication status on admission, impacts patient outcomes. In this study, we examine varying levels of alcohol use in burn patients and its impact on both short- and long-term outcomes., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Paraquat dichloride is a widely used, highly toxic chemical herbicide and a significant cause of fatal poisonings. Toxicity is thought to be secondary to generation of reactive oxygen species. Hours after exposure, patients may experience signs and symptoms ranging from nausea to multisystem organ failure. To mitigate complications and death, immunosuppression with cyclophosphamide and corticosteroid-based therapies has shown to be an effective option in limited studies. Our objective is to report our center's experience treating patients that had been exposed to paraquat over a 2-day period. Patients were identified using our Institutional Burn Center registry and linked to the clinical and administrative data. Demographics, length of stay (LOS), costs, and mortality were evaluated. There were nine patients admitted from the exposure. All were male. All survived. Eight were undocumented migrant farmers. The average age was 36 years (25-59 years). The average LOS was 3.3 days (2-5 days). Seventy-eight percent had cutaneous injury, but only one required debridement and placement of a skin substitute. Thirty-three percent complained of continued shortness of breath after discharge. Average total hospital cost was $28,131 ($9,500-$51,000). Paraquat is a highly toxic herbicide and exposure can be fatal if not treated promptly. Immediate decontamination and repeated pulse therapy with cyclophosphamide and methylprednisolone may be life-saving., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The Rockwood Clinical Frailty Scale is a validated rapid assessment of frailty phenotype and predictor of mortality in the geriatric population. Using data from a large tertiary care burn center, we assessed the association between admission frailty in an elderly burn population and inpatient outcomes. This was a retrospective analysis of burn patients ≥65 years from 2015 to 2019. Patients were assigned to frailty subgroups based on comprehensive medical, social work, and therapy assessments. Cox proportional hazards regression was used to estimate associations between admission frailty and 30-day inpatient mortality. Our study included 644 patients (low frailty: 262, moderate frailty: 345, and high frailty: 37). Frailty was associated with higher median TBSA and age at admission. The 30-day cumulative incidence of mortality was 2.3%, 7.0%, and 24.3% among the low, moderate, and high frailty strata, respectively. After adjustment for age, TBSA, and inhalation injury, high frailty was associated with increased 30-day mortality, compared to low (hazard ratio 5.73; 95% confidence interval 1.86, 17.62). Moderate frailty also appeared to increase 30-day mortality, although estimates were imprecise (hazard ratio 2.19; 95% confidence interval 0.87-5.50). High frailty was associated with increased morbidity and healthcare utilization, including need for intensive care stay (68% vs 37% and 21%, P < .001) and rehab or care facility at discharge (41% vs 25% and 6%, P < .001), compared to moderate and low frailty subgroups. Our findings emphasize the need to consider preinjury physiological state and the increased risk of death and morbidity in the elderly burn population., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The use of alcohol and illicit substances has been associated with impaired judgment and health, but the effect on inpatient outcomes after burn injury remains unsettled. Our objective was to evaluate the effect of alcohol and illicit substance use on our inpatient burn outcomes. Adult patients admitted with burn injury-including inhalation injury only-between January 1, 2014 and June 30, 2019 were eligible for inclusion. Alcohol use and illicit drug use were identified on admission. Outcomes of interest included requiring mechanical ventilation, admission to the intensive care unit, length of stay, and inpatient mortality. Multivariable linear and logistic regression models were used to estimate the effects of use on inpatient outcomes. A total of 3476 patients were included in our analyses; 8% (n = 284) tested positive for alcohol, 10% (n = 364) tested positive for cocaine, and 27% (n = 930) tested positive for marijuana and at admission. Two hundred and eighty adults (18% of all positive patients) tested positive for at least two substances. Patients who tested positive for alcohol had longer lengths of stay and were more likely to be admitted to the intensive care unit. Patients who tested positive for cocaine had longer overall and intensive care unit lengths of stay. No differences in inpatient outcomes were seen among patients who tested positive for marijuana. Neither alcohol nor illicit substance use appears to affect inpatient mortality after burns. Alcohol and cocaine use significantly increased overall length of stay. Marijuana use had no impact on inpatient outcomes., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In this retrospective analysis, we investigated the rate of radiologically confirmed osteomyelitis, extremity amputation and healthcare utilization in both the diabetic and non-diabetic lower extremity burn populations to determine the impact of diabetes mellitus on these outcomes. The burn registry was used to identify all patients admitted to our tertiary burn center from 2014 to 2018. Only patients with lower extremity burns (foot and/or ankle) were included. Statistical analysis was performed using Student's t test, chi-squared test, and Fischer's exact test. Of the 315 patients identified, 103 had a known diagnosis of diabetes mellitus and 212 did not. Seventeen patients were found to have osteomyelitis within three months of the burn injury. Fifteen of these patients had a history of diabetes. Notably, when non-diabetics were diagnosed with osteomyelitis, significant differences were observed in both length of stay and cost in comparison to their counterparts without osteomyelitis (36 vs 9 days; p=0.0003; $226,289 vs $48,818, p=0.0001). Eleven patients required an amputation and 10 (90.9%) of these patients had comorbid diabetes and documented diabetic neuropathy. Compared to non-diabetics, the diabetic cohort demonstrated both a higher average length of stay (13.7 vs 9.2 days, p-value=0.0016) and hospitalization cost ($72,883 vs $50,500, p-value=0.0058). Our findings highlight that diabetic patients with lower extremity burns are more likely to develop osteomyelitis than their non-diabetic counterparts and when osteomyelitis is present, diabetic patients have an increased amputation rate. Further study is required to develop protocols to treat this population, with the specific goal of minimizing patient morbidity and optimizing healthcare utilization., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Burn injured patients are at high risk of thromboembolic complications. Morbid obesity further increases this risk. Our objective was to evaluate the efficacy of enoxaparin dosed 40 mg twice daily in achieving prophylactic plasma anti-Xa levels in obese burn patients. A retrospective chart review from November 2018 until September 2019 identified patients who were either ≥100 kg or had a body mass index ≥30 kg/m2 and initiated on enoxaparin 40 mg twice daily for venous thromboembolism prophylaxis. Patients were ≥18 yr of age and received ≥3 sequential doses of enoxaparin with appropriately timed peak plasma anti-Xa levels to monitor efficacy. One hundred forty-eight patients were screened with 43 patients included for analysis. Forty-two percent of the patients did not reach target peak plasma anti-Xa levels (0.2-0.5 IU/ml) on enoxaparin 40 mg twice daily. Patients who did not meet prophylactic target levels were more likely to be male (P < 0.05) and have an increased mean body weight (129 ± 24 kg vs 110 ± 16 kg, P < 0.05). Thirteen out of 18 patients received dosage adjustments with subsequent anti-Xa levels available for follow-up assessment, of which an additional six patients required further dosage adjustment to meet prophylactic goals. Current utilization of a fixed 40 mg twice daily regimen of enoxaparin for venous thromboembolism (VTE) is inadequate to meet target prophylactic peak plasma anti-Xa levels in the obese burn patient population. Dose adjusting enoxaparin to target anti-Xa levels to reduce VTE rates in obese burn patients should be further evaluated., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The ramifications from the 2019 severe acute respiratory syndrome coronavirus 2 (COVID-19) pandemic caused by the novel corona virus will be felt globally for years to come. Mandates to shelter-in-place were called in nearly every state to limit viral exposure. The impact of the mandate on acute burn admissions was unknown. Our objective was to assess the impact of a shelter-in-place order on acute burn admissions at our burn center. All patients admitted to the burn center with burn injuries- including inhalation injury only- and desquamating skin disorders between March 10th to May 22nd, 2020 were eligible for inclusion. We compared all burn center admissions to a month-matched historical cohort from 2019, and summertime admissions for the last five years. Statistical significance was accepted as p < 0.05. There was a 9% increase in pediatric admissions after the shelter-in-place order. Compared to the 2019 cohort, there was a 28% increase in admissions of school aged children in 2020. This was not statistically significant. While the purpose of the "shelter-in-place" mandate was to reduce viral transmission of COVID-19, it consequently led to an increased percentage of admissions of school age children- comparable to our summertime numbers. More outreach and education are needed to provide safe resources for families during this pandemic., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s).)

The features of work-related burn (WRB) injuries are not well defined in the literature and they vary depending on geographical location. We wanted to describe these characteristics among patients treated in the UNC Burn Center to evaluate the potential impact of commonly accepted prevention efforts. Adults of working age, admitted between January 1, 2013, and December 31, 2018, were identified using our Burn Center Registry. Demographic data, characteristics of injury, course of treatment, and patients' outcomes were described. Differences between work-related and non-work-related injuries were evaluated using the Chi-square test and Student t-test where appropriate. Three thousand five hundred and forty-five patients were included. WRB cases constituted 18% of the study population, and this proportion remained relatively stable during the study timeframe. Young white males were the majority of this group. When compared with non-WRB patients, they were characterized by fewer co-morbidities, decreased TBSA burns, decreased risk of inhalation injury, shorter time of intensive care treatment, shorter lengths of hospital stay, and lower treatment cost. In contrast to non-WRB, among which flame injuries were the main reason for admission, work-related patients most often suffered scald burns. They also had a dramatically increased proportion of chemical and electrical burns, making the latter the most common cause of death in that group. WRB are characterized by a characteristic patient profile, burn etiologies, and outcomes. Learning specific patterns at this group may contribute to optimize work safety regulations and medical interventions., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In patients with diabetes mellitus (DM), amputation rates exceed 30% when lower extremity osteomyelitis is present. We sought to determine the rate of osteomyelitis and any subsequent amputation in our patients with DM and lower extremity burns. We performed a single-site, retrospective review at our burn center using the institutional burn center registry, linked to clinical and administrative data. Adults (≥18 years old) with DM admitted from January 1, 2014 to December 31, 2018 for isolated lower extremity burns were eligible for inclusion. We evaluated demographics, burn characteristics, comorbidities, presence of radiologically confirmed osteomyelitis, length of stay (LOS), inpatient hospitalization costs, and amputation rate at 3 months and 12 months after injury. We identified 103 patients with DM and isolated lower extremity burns. Of these, 88 patients did not have osteomyelitis, while 15 patients had radiologically confirmed osteomyelitis within 3 months of the burn injury. Compared to patients without osteomyelitis, patients with osteomyelitis had significantly increased LOS (average LOS 22.7 days vs 12.1 days, P = .0042), inpatient hospitalization costs (average $135,345 vs $62,237, P = .0008), amputation rate within 3 months (66.7% vs 5.70%, P < .00001), and amputation rate within 12 months (66.7% vs 9.1%, P < .0001). The two groups were otherwise similar in demographics, burn injury characteristics, access to healthcare, and preexisting comorbidities. Patients with DM and lower extremity burns incurred increased LOS, higher inpatient hospitalization costs, and increased amputation rates if radiologically confirmed osteomyelitis was present within 3 months of the burn injury., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Alcohol and illicit drug use are common among burn-injured patients. Urine toxicology and alcohol screens are a part of our admission order sets and automatically ordered for all adult patients. Our objective was to determine the impact of bias in screening compliance and compare those results to patients who test positive. All adult patients admitted between January 1 st , 2014 and December 31 st , 2018 were eligible for inclusion. Multivariable logistic regression was used to identify potential predictors for compliance in obtaining samples for screens, and patient characteristics associated with testing positive. Four thousand nine hundred ninety-eight patients were included in the study. The biggest predictors for compliance in obtaining samples for screens were inhalation injury, intensive care unit stay, length of stay, burn size, and current smoking status. No differences in compliance with screens were seen across age, race, or ethnicity. Current smokers and patients with a history of major psychiatric illness were more likely to test positive for alcohol and illicit drugs. Non-Hispanic Black patients were more likely to test positive for illicit drugs. Male sex and pre-existing psychiatric conditions were significant predictors for compliance for alcohol screens, and, positive tests. Implicit bias based on age, race, or ethnicity played no predictive role in compliance for either screen, however, non-Hispanic Blacks were more likely to test positive for illicit drugs. More studies are needed to understand the effect of selection bias related to sample collection, and the significance of positive test results., Competing Interests: None., (IJBT Copyright © 2020.)

The art of pyrography, burning designs in wood, dates back to prehistory. Risks of traditional techniques included cutaneous burns and airway injury. Fractal wood burning is a niche technique using a high-voltage electrical source to burn branched designs into wood. While this technique has grown in popularity, the associated risks are not well understood. We describe a patient who presented to our burn center after sustaining high-voltage electrical injuries while making fractal wood art using an improvised a high-voltage transformer. During the wood-burning process, he contacted the electrodes and suffered full-thickness electrical burns to the neck, chest, and bilateral upper extremities. Bilateral upper extremity fasciotomies were performed on admission. Multiple subsequent operations culminated with autografting to most of the wounds and complex reconstruction of the left thumb. In evaluating online news reports, we found 25 unique individuals with death or injury attributed to fractal wood burning from July 2016 to January 2020. Five sustained substantial injuries, while 20 reportedly died. Ages ranged from 17 years old to the 60s. One death and one injury occurred in females, with the remainder of reports involving males. Of the survivors, four sustained significant upper extremity electrical injuries and three suffered cardiac arrest at the time of injury. Fractal wood burning is associated with devastating high-voltage electrical injuries and death. Prevention efforts should be focused on education about the potential for death and permanently disabling injuries from this art form., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Supply and demand dictate resource allocation in large academic institutions. Classic teaching is that burns is a seasonal specialty with winter being the "busiest" time of year. Resident allocation during the winter and summer months, however, is traditionally low due to the holidays and travel peaks. Our objective was to evaluate our acuity-defined as patient complexity-based on seasons, in order to petition for appropriate mid-level provider allocation. We performed a retrospective review of all admissions to an accredited, large academic burn center. All patients admitted between January 1, 2009 and December 31, 2018 were eligible for inclusion. Demographics, length of stay, injury characteristics, and mortality were evaluated. Thirteen thousand four hundred fifty-eight patients were admitted during this study period. Most patients were admitted during the summer. Patients admitted to the intensive care unit were more likely to be admitted in the winter, although this was not statistically significant. Winter admissions had the longest lengths of stay, and the highest incidence of inhalation injury. Female and elderly patients were more likely admitted during the winter. There was a significant difference in mortality between summer and winter seasons. Acuity is seasonal in our large academic burn center and resource allocation should align with the needs of the patients. This data may help large centers petition their institutions for more consistent experienced mid-level providers, specifically during critical seasons., (© American Burn Association 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Among burn patients, research is conflicted, but may suggest that females are at increased risk of mortality, despite the opposite being true in non-burn trauma. Our objective was to determine whether sex-based differences in burn mortality exist, and assess whether patient demographics, comorbid conditions, and injury characteristics explain said differences., Methods: Adult patients admitted with burn injury-including inhalation injury only-between 2004 and 2013 were included. Inverse probability of treatment weights (IPTW) and inverse probability of censor weights (IPCW) were calculated using admit year, patient demographics, comorbid conditions, and injury characteristics to adjust for potential confounding and informative censoring. Standardized Kaplan-Meier survival curves, weighted by both IPTW and IPCW, were used to estimate the 30-day and 60-day risk of inpatient mortality across sex., Results: Females were older (median age 44 vs. 41 years old, p < 0.0001) and more likely to be Black (32% vs. 25%, p < 0.0001), have diabetes (14% vs. 10%, p < 0.0001), pulmonary disease (14% vs. 7%, p < 0.0001), heart failure (4% vs. 2%, p = 0.001), scald burns (45% vs. 26%, p < 0.0001), and inhalational injuries (10% vs. 8%, p = 0.04). Even after weighting, females were still over twice as likely to die after 60 days (RR 2.87, 95% CI 1.09, 7.51)., Conclusion: Female burn patients have a significantly higher risk of 60-day mortality, even after accounting for demographics, comorbid conditions, burn size, and inhalational injury. Future research efforts and treatments to attenuate mortality should account for these sex-based differences. The project was supported by the National Institutes of Health, Grant Number UL1TR001111.

Background: Over the ages, the use of leeches in medicine has evolved from haphazard bloodletting to a well-understood physiologic process with defined, rational applications., Objective: The authors describe the current role of leech therapy in cutaneous surgery and medicine., Methods: Case series and review of the literature., Results: Leech saliva contains anticoagulative, anti-aggregative and vasodilatory components. Combined with the annelid's mechanical ability to extract blood, leeches can contribute to patients' health with minimal risks., Conclusion: Leeches should be considered as novel therapies for disorders of coagulation and venous congestion. Implementation of leech treatment should be tempered with the potential adverse effects, including Aeromonas infection and a drop in hematocrit that might require a blood transfusion.

Background: Nuclear translocation and DNA binding of the nuclear factor kappaB (NF-kappaB) is an early event in inflammatory cell activation in response to stimulation with bacterial components or cytokines. Cell activation via different receptors culminates in a common pathway leading to NF-kappaB activation and proinflammatory cytokine induction. We have previously shown that acute alcohol inhibits NF-kappaB activation by lipopolysaccharide (LPS) in human monocytes. Here we investigated whether acute alcohol treatment of human monocytes also inhibits NF-kappaB when induced through activation of the interleukin (IL)-1 or tumor necrosis factor (TNF) receptors., Methods: Human peripheral blood monocytes were treated with LPS, TNFalpha, and IL-1beta in the presence or absence of 25mM alcohol for 1 hr. NF-kappaB activation was determined by electrophoretic mobility shift assays using nuclear extracts. Inhibitory kappaB(alpha) (IkappaB(alpha)) was estimated by Western blotting in cytoplasmic extracts. Chinese hamster ovary cells expressing human CD14 were treated with LPS in the presence or absence of alcohol to study NF-kappaB and IkappaB(alpha) regulation., Results: Our results indicate that acute alcohol inhibits IL-1beta- and TNFalpha-induced NF-kappaB activation. We further show in CD14/toll-like receptor 4-expressing Chinese hamster ovary cells the specificity of alcohol-mediated inhibition of NF-kappaB via the toll-like receptor 4/CD14 receptors. Inhibition of NF-kappaB by acute alcohol was concomitant with decreased levels of the IkappaB(alpha) molecule in the cytoplasm of LPS, IL-1, and TNFalpha-activated monocytes., Conclusions: These data suggest a unique, IkappaB(alpha)-independent pathway for the inhibition of NF-kappaB activation by acute alcohol in monocytes. Universal inhibition of NF-kappaB by acute alcohol via these various receptor systems suggests a target for the effects of alcohol in the NF-kappaB activation cascade that is downstream from IkappaB(alpha) degradation. Further, these results demonstrate that acute alcohol is a potent inhibitor of NF-kappaB activation by mediators of early (LPS) or late (IL-1, TNF(alpha)) stages of inflammation in monocytes.