Performance of ABCD-10 and SCORTEN mortality prediction models in a cohort of patients with Stevens-Johnson syndrome/toxic epidermal necrolysis.

BACKGROUND: Age, bicarbonate, cancer, dialysis, 10% body surface area risk model (ABCD-10) has recently been proposed as an alternative to the SCORe of toxic epidermal necrolysis (SCORTEN) model for predicting in-hospital mortality in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). In contrast to SCORTEN, ABCD-10 incorporates prior dialysis and upweights the impact of cancer. OBJECTIVE: To determine the performance of ABCD-10 compared with that of SCORTEN in mortality prediction at a large, tertiary burn center. METHODS: A retrospective analysis of 192 patients with SJS/TEN admitted to the North Carolina Jaycee Burn Center from January 1, 2009, to December 31, 2019, was conducted. Data on these patients were collected using the burn registry and a manual chart review. The performance of both the mortality prediction models was assessed using univariate logistic regression and the Hosmer-Lemeshow test. RESULTS: The overall mortality was 22% (n = 43). Nine (5%) patients had cancer, and 7 (4%) had undergone prior dialysis; neither factor was associated with mortality (P = .11 and P = .62, respectively). SCORTEN was well calibrated to predict inpatient mortality (P = .82), whereas ABCD-10 appeared to have a poorer fit (P < .001) in these patients. Both the models showed good discrimination. LIMITATIONS: Small sample size. CONCLUSION: SCORTEN was a better predictor of inpatient mortality than ABCD-10 in a North American cohort of patients treated at the tertiary burn center.

Sex-Based Differences in Inpatient Burn Mortality.

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.

Specific Etiologies Associated With the Multiple Organ Dysfunction Syndrome in Children: Part 2.

OBJECTIVE: To describe a number of conditions and therapies associated with multiple organ dysfunction syndrome presented as part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Multiple Organ Dysfunction Workshop (March 26-27, 2015). In addition, the relationship between burn injuries and multiple organ dysfunction syndrome is also included although it was not discussed at the workshop. DATA SOURCES: Literature review, research data, and expert opinion. STUDY SELECTION: Not applicable. DATA EXTRACTION: Moderated by an expert from the field, issues relevant to the association of multiple organ dysfunction syndrome with a variety of conditions and therapies were presented, discussed, and debated with a focus on identifying knowledge gaps and the research priorities. DATA SYNTHESIS: Summary of presentations and discussion supported and supplemented by relevant literature. CONCLUSIONS: Sepsis and trauma are the two conditions most commonly associated with multiple organ dysfunction syndrome both in children and adults. However, many other pathophysiologic processes may result in multiple organ dysfunction syndrome. In this article, we discuss conditions such as liver failure and pancreatitis, pathophysiologic processes such as ischemia and hypoxia, and injuries such as trauma and burns. Additionally, therapeutic interventions such as medications, blood transfusions, transplantation may also precipitate and contribute to multiple organ dysfunction syndrome. The purpose of this article is to describe the association of multiple organ dysfunction syndrome with a variety of conditions and therapies in an attempt to identify similarities, differences, and opportunities for therapeutic intervention.

Reliable scar scoring system to assess photographs of burn patients.

BACKGROUND: Several scar-scoring scales exist to clinically monitor burn scar development and maturation. Although scoring scars through direct clinical examination is ideal, scars must sometimes be scored from photographs. No scar scale currently exists for the latter purpose. MATERIALS AND METHODS: We modified a previously described scar scale (Yeong et al., J Burn Care Rehabil 1997) and tested the reliability of this new scale in assessing burn scars from photographs. The new scale consisted of three parameters as follows: scar height, surface appearance, and color mismatch. Each parameter was assigned a score of 1 (best) to 4 (worst), generating a total score of 3-12. Five physicians with burns training scored 120 representative photographs using the original and modified scales. Reliability was analyzed using coefficient of agreement, Cronbach alpha, intraclass correlation coefficient, variance, and coefficient of variance. Analysis of variance was performed using the Kruskal-Wallis test. Color mismatch and scar height scores were validated by analyzing actual height and color differences. RESULTS: The intraclass correlation coefficient, the coefficient of agreement, and Cronbach alpha were higher for the modified scale than those of the original scale. The original scale produced more variance than that in the modified scale. Subanalysis demonstrated that, for all categories, the modified scale had greater correlation and reliability than the original scale. The correlation between color mismatch scores and actual color differences was 0.84 and between scar height scores and actual height was 0.81. CONCLUSIONS: The modified scar scale is a simple, reliable, and useful scale for evaluating photographs of burn patients.

Where we stand with human hypertrophic and keloid scar models.

We have yet to create a human scar model that demonstrates the complex nature of hypertrophic scar and keloid formation as well as ways to prevent them despite emerging advances in our understanding of the immune system, the inflammatory response, and proteomic and genomic changes after injury. Despite more complex in vitro models, we fail to explain the fundamental principles to scar formation, and the timeline of their development. The solution to developing the ideal in vitro scar model is one that mimics the heterogeneous cellular and molecular interactions, as well as the evolving structure and function of human skin.

Neighborhood child opportunity is associated with hospital length of stay following pediatric burn injury.

INTRODUCTION: Pediatric burns are associated with socioeconomic disadvantage and lead to significant morbidity. The Child Opportunity Index (COI) is a well-validated measure of neighborhood characteristics associated with healthy child development. We sought to evaluate the relationship between COI and outcomes of burn injuries in children. METHODS: We performed a single-institution retrospective review of pediatric (<16 years) burn admissions between 2015 and 2019. Based on United States residential zip codes, patients were stratified into national COI quintiles. We performed a multivariate Poisson regression analysis to determine the association between COI and increased length of stay. RESULTS: 2095 pediatric burn admissions occurred over the study period. Most children admitted were from very low (n = 644, 33.2 %) and low (n = 566, 29.2 %) COI neighborhoods. The proportion of non-Hispanic Black patients was significantly higher in neighborhoods with very low (44.5 %) compared to others (low:28.8 % vs. moderate:11.9 % vs. high:10.5 % vs. very high:4.3 %) (p < 0.01). Hospital length of stay was significantly longer in patients from very low COI neighborhoods (3.6 ± 4.1 vs. 3.2 ± 4.9 vs. 3.3 ± 4.8 vs. 2.8 ± 3.5 vs. 3.2 ± 8.1) (p = 0.02). On multivariate regression analysis, living in very high COI neighborhoods was associated with significantly decreased hospital length of stay (IRR: 0.51; 95 % CI: 0.45-0.56). CONCLUSION: Children from neighborhoods with significant socioeconomic disadvantage, as measured by the Child Opportunity Index, had a significantly higher incidence of burn injuries resulting in hospital admissions and longer hospital length of stay. Public health interventions focused on neighborhood-level drivers of childhood development are needed to decrease the incidence and reduce hospital costs in pediatric burns. TYPE OF STUDY: Retrospective study LEVEL OF EVIDENCE: Level III.

Mild obesity is protective after severe burn injury.

OBJECTIVE: To assess the impact of obesity on morbidity and mortality in severely burned patients. BACKGROUND: Despite the increasing number of people with obesity, little is known about the impact of obesity on postburn outcomes. METHODS: A total of 405 patients were prospectively enrolled as part of the multicenter trial Inflammation and the Host Response to Injury Glue Grant with the following inclusion criteria: 0 to 89 years of age, admitted within 96 hours after injury, and more than 20% total body surface area burn requiring at least 1 surgical intervention. Body mass index was used in adult patients to stratify according to World Health Organization definitions: less than 18.5 (underweight), 18.5 to 29.9 (normal weight), 30 to 34.9 (obese I), 35 to 39.9 (obese II), and body mass index more than 40 (obese III). Pediatric patients (2 to ≤18 years of age) were stratified by using the Centers for Disease Control and Prevention and World Health Organization body mass index-for-age growth charts to obtain a percentile ranking and then grouped as underweight (<5th percentile), normal weight (5th percentile to <95th percentile), and obese (≥95th percentile). The primary outcome was mortality and secondary outcomes were clinical markers of patient recovery, for example, multiorgan function, infections, sepsis, and length of stay. RESULTS: A total of 273 patients had normal weight, 116 were obese, and 16 were underweight; underweight patients were excluded from the analyses because of insufficient patient numbers. There were no differences in primary and secondary outcomes when normal weight patients were compared with obese patients. Further stratification in pediatric and adult patients showed similar results. However, when adult patients were stratified in obesity categories, log-rank analysis showed improved survival in the obese I group and higher mortality in the obese III group compared with obese I group (P < 0.05). CONCLUSIONS: Overall, obesity was not associated with increased morbidity and mortality. Subgroup analysis revealed that patients with mild obesity have the best survival, whereas morbidly obese patients have the highest mortality. (NCT00257244).

Burn size and survival probability in paediatric patients in modern burn care: a prospective observational cohort study.

BACKGROUND: Patient survival after severe burn injury is largely determined by burn size. Modern developments in burn care have greatly improved survival and outcomes. However, no large analysis of outcomes in paediatric burn patients with present treatment regimens exists. This study was designed to identify the burn size associated with significant increases in morbidity and mortality in paediatric patients. METHODS: We undertook a single-centre prospective observational cohort study using clinical data for paediatric patients with burns of at least 30% of their total body surface area (TBSA). Patients were stratified by burn size in 10% increments, ranging from 30% to 100% TBSA, with a secondary assignment made according to the outcome of a receiver operating characteristic (ROC) analysis. Statistical analysis was done with Student's t test, χ(2) test, logistic regression, and ROC analysis, as appropriate, with significance set at p<0·05. FINDINGS: 952 severely burned paediatric patients were admitted to the centre between 1998 and 2008. All groups were comparable in age (mean 7·3 [SD 5·3] years, ranging from 6·1 [5·1] years in the 30-39% TBSA group to 9·6 [5·4] years in the 90-100% TBSA group) and sex distribution (628 [66%] boys, ranging from 59% [73/123] in the 60-69% TBSA group to 82% [42/51] in the 90-100% TBSA group). 123 (13%) patients died (increasing from 3% [five of 180] in the 30-39% TBSA group to 55% [28/51] in the 90-100% TBSA group; p<0·0001), 154 (16%) developed multiorgan failure (increasing from 6% [ten] in the 30-39% TBSA group to 45% [23] in the 90-100% TBSA group; p<0·0001), and 89 (9%) had sepsis (increasing from 2% [three] in the 30-39% TBSA group to 26% [13] in the 90-100% TBSA group; p<0·0001). Burn size of 62% TBSA was a crucial threshold for mortality (odds ratio 10·07, 95% CI 5·56-18·22, p<0·0001). INTERPRETATION: We established that, in a modern paediatric burn care setting, a burn size of roughly 60% TBSA is a crucial threshold for postburn morbidity and mortality. On the basis of these findings, we recommend that paediatric patients with greater than 60% TBSA burns be immediately transferred to a specialised burn centre. Furthermore, at the burn centre, patients should be treated with increased vigilance and improved therapies, in view of the increased risk of poor outcome associated with this burn size. FUNDING: Shriners Hospitals for Children, US National Institutes of Health, US National Institute on Disability and Rehabilitation Research, Institute for Translational Sciences, CFI Leaders Opportunity Fund, Physicians' Services Incorporated Foundation.

The Cost of Mental Health Comorbid Conditions in Burn Patients: A Single-site Experience.

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.

Outcomes in Pediatric Burn Patients With Additional Trauma-Related Injuries.

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.

Does A History of Malignancy Lead to Worse Outcomes in a Single-center Burn Unit?

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.

Outcomes of COPD Patients with Flame Burn and Inhalation Injuries at a Single Institution.

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.

Long-term propranolol use in severely burned pediatric patients: a randomized controlled study.

OBJECTIVE: To determine the safety and efficacy of propranolol given for 1 year on cardiac function, resting energy expenditure, and body composition in a prospective, randomized, single-center, controlled study in pediatric patients with large burns. BACKGROUND: Severe burns trigger a hypermetabolic response that persists for up to 2 years postburn. Propranolol given for 1 month postburn blunts this response. Whether propranolol administration for 1 year after injury provides a continued benefit is currently unclear. METHODS: One-hundred seventy-nine pediatric patients with more than 30% total body surface area burns were randomized to control (n = 89) or 4 mg/kg/d propranolol (n = 90) for 12 months postburn. Changes in resting energy expenditure, cardiac function, and body composition were measured acutely at 3, 6, 9, and 12 months postburn. Statistical analyses included techniques that adjusted for non-normality, repeated-measures, and regression analyses. P < 0.05 was considered significant. RESULTS: Long-term propranolol treatment significantly reduced the percentage of the predicted heart rate and percentage of the predicted resting energy expenditure, decreased accumulation of central mass and central fat, prevented bone loss, and improved lean body mass accretion. There were very few adverse effects from the dose of propranolol used. CONCLUSIONS: Propranolol treatment for 12 months after thermal injury, ameliorates the hyperdynamic, hypermetabolic, hypercatabolic, and osteopenic responses in pediatric patients. This study is registered at clinicaltrials.gov: NCT00675714.

Insights on Microsatellite Characteristics, Evolution, and Function From the Social Amoeba Dictyostelium discoideum.

Microsatellites are repetitive sequences commonly found in the genomes of higher organisms. These repetitive sequences are prone to expansion or contraction, and when microsatellite expansion occurs in the regulatory or coding regions of genes this can result in a number of diseases including many neurodegenerative diseases. Unlike in humans and other organisms, the social amoeba Dictyostelium discoideum contains an unusually high number of microsatellites. Intriguingly, many of these microsatellites fall within the coding region of genes, resulting in nearly 10,000 homopolymeric repeat proteins within the Dictyostelium proteome. Surprisingly, among the most common of these repeats are polyglutamine repeats, a type of repeat that causes a class of nine neurodegenerative diseases in humans. In this minireview, we summarize what is currently known about homopolymeric repeats and microsatellites in Dictyostelium discoideum and discuss the potential utility of Dictyostelium for identifying novel mechanisms that utilize and regulate regions of repetitive DNA.

COVID-induced toxic epidermal necrolysis in a 4-year-old female: a case report and literature review.

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.

Impact of Chronic Alcohol Use on Fluid Resuscitation in Burn Patients.

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.

Evaluation of Voriconazole and Posaconazole Dosing in Patients With Thermal Burn Injuries.

Fungal infections are a recognized cause of increased morbidity and mortality in thermal burn patients. Adequate treatment regimens remain a challenge due to unpredictable pharmacokinetic/pharmacodynamic changes caused by a hypermetabolic state and individual patient factors. A retrospective evaluation of adult thermal burn patients from April 2014 to April 2020 was conducted to assess voriconazole and posaconazole antifungal dosing regimens. The primary outcome was the incidence of attaining a therapeutic steady-state trough level on the patient's initial voriconazole or posaconazole regimen. Of the 33 patients analyzed, 26 (78.8%) patients achieved a therapeutic level during azole therapy. However, only 11 (33.3%) patients achieved a therapeutic level on their first azole regimen. The median time to therapeutic level was 8.0 + 21.8 days from the start of azole therapy. Optimal dosing strategies for azole therapy in patients with thermal burns remain undefined. Further assessment is needed to delineate patient-specific factors that can contribute to subtherapeutic azole levels in thermal burn patients and the overall clinical impact of population-specific dosing regimens.

Higher Admission Frailty Scores Predict Increased Mortality, Morbidity, and Healthcare Utilization in the Elderly Burn Population.

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.

Single-Center Experience With Paraquat Exposure in Nine Patients.

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.

Transcriptomic Response of Fusarium verticillioides to Variably Inhibitory Environmental Isolates of Streptomyces.

Fusarium verticillioides is a mycotoxigenic fungus that is a threat to food and feed safety due to its common infection of maize, a global staple crop. A proposed strategy to combat this threat is the use of biological control bacteria that can inhibit the fungus and reduce mycotoxin contamination. In this study, the effect of multiple environmental isolates of Streptomyces on F. verticillioides was examined via transcriptome analysis. The Streptomyces strains ranged from inducing no visible response to dramatic growth inhibition. Transcriptionally, F. verticillioides responded proportionally to strain inhibition with either little to no transcript changes to thousands of genes being differentially expressed. Expression changes in multiple F. verticillioides putative secondary metabolite gene clusters was observed. Interestingly, genes involved in the fusaric acid gene cluster were suppressed by inhibitory strains of Streptomyces. A F. verticillioides beta-lactamase encoding gene (FVEG_13172) was found to be highly induced by specific inhibitory Streptomyces strains and its deletion increased visible response to those strains. This study demonstrates that F. verticillioides does not have an all or nothing response to bacteria it encounters but rather a measured response that is strain specific and proportional to the strength of inhibition.