Thermal injury induces concurrent inflammatory and immune dysfunction, which is associated with adverse clinical outcomes. However, these effects in the pediatric population are less studied and there is no standard method to identify those at risk for developing infections. Our goal was to better understand immune dysfunction and identify soluble protein markers following pediatric thermal injury. Further we wanted to determine which early inflammatory, soluble, or immune function markers are most predictive of the development of nosocomial infections (NI) after burn injury. We performed a prospective observational study at a single American Burn Association-verified Pediatric Burn Center. A total of 94 pediatric burn subjects were enrolled and twenty-three of those subjects developed a NI with a median time to diagnosis of 8 days. Whole blood samples, collected within the first 72 hours after injury, were used to compare various markers of inflammation, immune function, and soluble proteins between those who recovered without developing an infection and those who developed a NI after burn injury. Within the first three days of burn injury, innate and adaptive immune function markers (ex vivo lipopolysaccharide-induced tumor necrosis factor alpha production capacity, and ex vivo phytohemagglutinin-induced interleukin-10 production capacity, respectively) were decreased for those subjects who developed a subsequent NI. Further analysis of soluble protein targets associated with these pathways displayed significant increases in soluble CD27, BTLA, and TIM-3 for those who developed a NI. Our findings indicate that suppression of both the innate and adaptive immune function occurs concurrently within the first 72 hours following pediatric thermal injury. At the same time, subjects who developed NI have increased soluble protein biomarkers. Soluble CD27, BTLA, and TIM-3 were highly predictive of the development of subsequent infectious complications. This study identifies early soluble protein makers that are predictive of infection in pediatric burn subjects. These findings should inform future immunomodulatory therapeutic studies.
Background: There is currently no standard definition of a severe burn in the pediatric patient population to identify those at higher risk of infectious complications. Our aim was to correlate total burn surface area (TBSA), burn depth, and type of burn injury to nosocomial infection rates and systemic immune system responses to better define risk factors associated with adverse outcomes. Methods: A prospective observational study at a single-center, quaternary-care, American Burn Association–verified pediatric burn center was conducted from 2016 to 2021. Blood was collected within 72 h of injury from 103 pediatric patients. Whole blood was incubated with lipopolysaccharide or phytohemagglutinin stimulation reagent to measure innate and adaptive immune response, respectively. Flow cytometry was performed on whole blood samples to measure both innate and adaptive immune cells. Unstimulated plasma was also extracted, and IL-6 and IL-10 as well as soluble proteins B- and T-lymphocyte attenuator, CD27, and T-cell immunoglobulin mucin 3 were quantified. Results: There was a significant increased risk for nosocomial infection in pediatric patients with TBSA burns of ≥20%, full-thickness burn injuries ≥5%, or flame burn injuries. There was an overall decrease in both innate and adaptive immune function in patients with TBSA burns ≥20% or full-thickness burn injuries ≥5%. Both burn injury characteristics were also associated with a significant increase in unstimulated IL-6 and IL-10 and soluble immunoregulatory checkpoint proteins. We observed a significant decrease in soluble B- and T-lymphocyte attenuator for those with a flame injury, but there were no other differences between flame injury and scald/contact burns in terms of innate and adaptive immune function. Conclusion: Burns with ≥20% TBSA or ≥5% full thickness in pediatric patients are associated with systemic immune dysfunction and increased risk of nosocomial infections.
Introduction: Treatment of infants with hypoplastic left heart syndrome (HLHS) remains challenging, and those affected remain with significant risks for mortality and morbidity throughout their lifetimes. The maternal-fetal environment (MFE) has been shown to affect outcomes for infants with HLHS after the Norwood procedure. The hybrid procedure, comprised of both catheterization and surgical components, is a less invasive option for initial intervention compared to the Norwood procedure. It is unknown how the MFE impacts outcomes following the hybrid procedure. Methods: This is a single-center, retrospective study of infants born with HLHS who underwent hybrid palliation from January 2009-August 2021. Predictor variables analyzed included fetal, maternal, and postnatal factors. The primary outcome was mortality prior to Stage II palliation.Results: We studied a 144-subject cohort. There was a statistically significant difference in mortality prior to stage II palliation in infants with prematurity, small for gestational age, and aortic atresia subtype (p<0.001, p=0.009, and p=0.008, respectively). There was no difference in mortality associated with maternal diabetes, hypertension, obesity, smoking or illicit drug use, or advanced maternal age. State and national area deprivation index scores were associated with increased risk of mortality in the entire cohort, such that infants born in areas with higher deprivation had a higher incidence of mortality.Conclusions: Several markers of an impaired MFE, including prematurity, small for gestational age, and higher deprivation index scores, are associated with mortality following hybrid palliation. Individual maternal comorbidities were not associated with higher mortality. The MFE may be a target for prenatal counseling and future interventions to improve pregnancy and neonatal outcomes in this population.
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