Legal epidemiology of paediatric dog bite injuries.

BACKGROUND: Dog bite injuries cause over 100 000 paediatric emergency department visits annually. Our objective was to analyse associations between regional dog ownership laws and incidence of paediatric dog bites. METHODS: This observational study used an online search to locate local dog-related policies within Ohio cities. Data collected by Ohio Partners For Kids from 2011 through 2020 regarding claims for paediatric dog bite injuries were used to compare areas with and without located policies and the incidence of injury. RESULTS: Our cohort consisted of 6175 paediatric patients with dog bite injury encounters. A majority were white (79.1%), male (55.0%), 0-5 years old (39.2%) and did not require hospital admission (98.1%). Seventy-nine of 303 cities (26.1%) had city-specific policies related to dogs. Overall, the presence of dog-related policies was associated with lower incidence of dog bite injury claims (p=0.01). Specifically, metropolitan areas and the Central Ohio region had a significantly lower incidence when dog-related policies were present (324.85 per 100 000 children per year when present vs 398.56 when absent; p<0.05; 304.87 per 100 000 children per year when present vs 411.43 when absent; p<0.05). CONCLUSIONS: The presence of city-specific dog-related policies is associated with lower incidence of paediatric dog bite injury claims, suggesting that local policy impacts this important public health issue. There are limited dog-related policies addressing dog bite prevention, with inconsistencies in breadth and depth. Creating consistent, practical requirements among policies with vigorous enforcement could ameliorate public health concerns from paediatric dog bite injuries.

Association of Race With Postoperative Mortality Following Major Abdominopelvic Trauma in Children.

BACKGROUND: The leading cause of mortality among children is trauma. Race and ethnicity are critical determinants of pediatric postsurgical outcomes, with minority children generally experiencing higher rates of postoperative morbidity and mortality than White children. This pattern of poorer outcomes for racial and/or ethnic minority children has also been demonstrated in children with head and limb traumas. While injuries to the abdomen and pelvis are not as common, they can be life-threatening. Racial and/or ethnic differences in outcomes of pediatric abdominopelvic operative traumas have not been examined. Our objective was to determine whether disparities exist in postoperative mortality among children with major abdominopelvic trauma. MATERIALS AND METHODS: We performed a retrospective analysis of the Healthcare Cost and Utilization Project Kids' Inpatient Database for 2003, 2006, 2009, and 2012. Patients were included if they were < 18 years, sustained a major abdominopelvic injury, and underwent subsequent surgical intervention. Our primary outcome was inpatient mortality, comparing children of different race and/or ethnicity. RESULTS: We identified a weighted cohort of 13,955 children, of whom 6765 (48.5%) were White, 3614 (25.9%) Black, and 2647 (19.0%) Hispanic. After adjusting for covariates, Black children were 94% more likely to die than their White peers (3.3% versus 1.6%, adjusted-RR:1.94, 95%CI: 1.33-2.82, P = 0.001). Hispanic children (adjusted-RR:1.99, 95%CI: 1.36-2.91, P < 0.001) and those of other race and/or ethnicity (adjusted-RR: 2.02, 95%CI:1.20-3.40, P = 0.008) were also more likely to die compared to their White peers. CONCLUSIONS: Black and Hispanic children who require operative intervention following major abdominopelvic trauma have a higher risk of postoperative mortality compared with White children.

Implementation of a Level 1 Neuro Trauma Activation at a Tertiary Pediatric Trauma Center.

INTRODUCTION: Timely management improves outcomes in patients with traumatic brain injury (TBI), especially those requiring operative intervention. We implemented a "Level 1 Neuro" (L1N) trauma activation for severe TBI, aiming to decrease times to intervention. METHODS: We evaluated whether an L1N activation was associated with shorter times to operating room (OR) incision and pediatric intensive care unit (PICU) admission using multivariable regression models. Trauma patients with severe TBI undergoing operative intervention or PICU admission from January 2008-October 2020 met inclusion. The L1N cohort included patients meeting our institution's L1N criteria. The L1 and L2 cohorts included head injury patients with hAIS ≥3 and an L1 or L2 activation, respectively. RESULTS: Median hAIS, GCS, Rotterdam CT score, and ISS were 4.5 (4-5), 8 (3-15), 2 (1-3), and 17 (11-26), respectively. We demonstrate clinically shorter times to OR incision among L1N traumas (93.3 min) compared to L1 (106.7 min; P = 0.73) and L2 cohorts (133.5 min; P = 0.03). We also demonstrate clinically shorter times to anesthesia among L1N traumas (51.9 min) compared to L1 (70.1 min; P = 0.13) and L2 cohorts (101.3 min; P < 0.01). Median GCS, ISS and hAIS in the PICU patients were 10 (IQR:3-15), 17 (11-26), and 4 (3-4), respectively. We demonstrate clinically shorter times to PICU among L1N traumas (82.1 min) and the L2 cohort (154.7 min; P < 0.01). CONCLUSIONS: An L1N activation is associated with shorter times to anesthesia and OR management. Enhancing communication with standardized neurotrauma activation has the potential to improve timeliness of care in severe pediatric TBI.

Pediatric burn care: new techniques and outcomes.

PURPOSE OF REVIEW: Thermal injury is a leading cause of morbidity and mortality in children. This review highlights the current management of thermal injury and its complications. RECENT FINDINGS: Many recent advances in burn care have improved the outcomes of patients with thermal injury; however, variability does exist, and there are many opportunities for improvement. This review will highlight the complexity of issues encountered along the continuum of care for thermal injury patients. Accurate estimation of total burn surface area (TBSA) of a burn continues to be a challenge in pediatric patients. Variability continues to exist surrounding the management of burn resuscitation and complex wounds. Children with extensive burns have profound immune and metabolic changes that can lead to multiple complications, including infections, growth arrest, and loss of lean body mass. Standardization in measurements related to quality of life and psychological stress following pediatric thermal injury is much needed. SUMMARY: The care of pediatric patients with thermal injury is complex and multifaceted. This review highlights the most recent advances in pediatric burn care.

Synergistic effects of sepsis and prematurity on neonatal postoperative mortality.

INTRODUCTION: Compared with term neonates, preterm babies are more likely to die from sepsis. However, the combined effects of sepsis and prematurity on neonatal postoperative mortality are largely unknown. Our objective was to quantify the proportion of neonatal postoperative mortality that is attributable to the synergistic effects of preoperative sepsis and prematurity. METHODS: We performed a multicentre, propensity-score-weighted, retrospective, cohort study of neonates who underwent inpatient surgery across hospitals participating in the United States National Surgical Quality Improvement Program-Pediatric (2012-2017). We assessed the proportion of the observed hazard ratio of mortality and complications that is attributable to the synergistic effect of prematurity and sepsis by estimating the attributable proportion (AP) and its 95% confidence interval (CI). RESULTS: We identified 19 312 neonates who realised a total of 321 321 person-days of postsurgical observations, during which 683 died (mortality rate: 2.1 per 1000 person-days). The proportion of mortality risk that is attributable to the synergistic effect of prematurity and sepsis was 50.5% (AP=50.5%; 95% CI, 28.8-72.3%; P < 0.001). About half of mortality events among preterm neonates with sepsis occurred within 24 h after surgery. Just over 45% of postoperative complications were attributable to the synergistic effect of prematurity and sepsis when both conditions were present (AP=45.8; 95% CI, 13.4-78.1%; P<0.001). CONCLUSION: Approximately half of postsurgical mortality and complications were attributable to the combined effect of sepsis and prematurity among neonates with both exposures. These neonates typically died within a few days after surgery, indicating a very narrow window of opportunity to predict and prevent mortality. CLINICAL TRIAL NUMBER AND REGISTRY: Not applicable.

Nosocomial Infection Following Severe Traumatic Injury in Children.

OBJECTIVES: Nosocomial infection is a common source of morbidity in critically injured children including those with traumatic brain injury. Risk factors for nosocomial infection in this population, however, are poorly understood. We hypothesized that critically ill pediatric trauma patients with traumatic brain injury would demonstrate higher rates of nosocomial infection than those without traumatic brain injury. DESIGN: Retrospective case-control study. SETTING: PICU, single institution. PATIENTS: Patients under 18 years old who were admitted to the PICU for at least 48 hours following a traumatic injury were included. Patients were admitted between September 2008 and December 2015. Patients with the following injury types were excluded: thermal injury, drowning, hanging/strangulation, acute hypoxic ischemic encephalopathy, or nonaccidental trauma. Data collected included demographics, injury information, hospital and PICU length of stay, vital signs, laboratory data, insertion and removal dates for invasive devices, surgeries performed, transfusions of blood products, and microbiology culture results. Initial Pediatric Risk of Mortality III and Pediatric Logistic Organ Dysfunction-2 scores were determined. Patients were classified as having: 1) an isolated traumatic brain injury, 2) a traumatic injury without traumatic brain injury, or 3) polytrauma with traumatic brain injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two hundred three patients were included in the analyses, and 27 patients developed a nosocomial infection. Patients with polytrauma with traumatic brain injury demonstrated a significantly higher infection rate (30%) than patients with isolated traumatic brain injury (6%) or traumatic injury without traumatic brain injury (9%) (p < 0.001). This increased rate of nosocomial infection was noted on univariate analysis, on multivariable analysis, and after adjusting for other risk factors. CONCLUSIONS: In this single-center, retrospective analysis of critically ill pediatric trauma patients, nosocomial infections were more frequently observed in patients admitted following polytrauma with traumatic brain injury than in patients with isolated traumatic brain injury or trauma without traumatic brain injury.

Impact of a Dedicated Advanced Practice Provider Model for Pediatric Trauma and Burn Patients.

BACKGROUND: A free-standing, academic Level 1 pediatric trauma and verified pediatric burn center created a dedicated trauma and burn service advanced practice provider role, and restructured rounds. The changes were implemented to improve patient care. METHODS: A pre and postintervention study using historical controls was performed to compare 18 months prior (preintervention) and 18 months following (postintervention) practice changes. Data collection included demographics, injury characteristics, length of stay (LOS), complications, and patient satisfaction results. RESULTS: When compared with the preintervention period, the postintervention period had a higher patient volume and an increased number of severely injured patients. Mean LOS was stable for all patients and trauma patients, as were the complication rates related to trauma and burns. However, the mean LOS/total body surface area (TBSA) burned decreased from 1.36 to 1.04 days/TBSA (p = .160) in burn patients and from 0.84 to 0.62 days/TBSA (p = .060) in those with more than 5% TBSA. Patient satisfaction scores were stable in the categories of nursing care and the child's physician. Despite an increase in the volume and severity of patients, there was a clinically meaningful decrease in burn patient LOS/TBSA. CONCLUSION: The addition of a dedicated advanced practice provider and restructured trauma service appears to provide a benefit to pediatric burn patients.

Prehospital Versus Trauma Center Glasgow Coma Scale in Pediatric Traumatic Brain Injury Patients.

BACKGROUND: Traumatic brain injury (TBI) is a major source of morbidity and mortality in children. The Glasgow Coma Scale (GCS) can be challenging to calculate in pediatric patients. Our objective was to determine its reproducibility between prehospital providers and pediatric trauma hospital personnel. MATERIALS AND METHODS: The institutional trauma database for a level 1 pediatric trauma center was queried for patients aged ≤18 y who presented with a TBI. Demographics, mechanism, prehospital GCS, and trauma center GCS were collected. Agreement was evaluated with weighted kappa (κ) coefficients (0 = agreement no better than that expected by chance alone, 1 = perfect agreement). RESULTS: The inclusion criteria were met by 1711 patients, 263 of whom were aged <3 y. Prehospital GCS and trauma center GCS differed in 766 patients (44.8%). Agreement between prehospital GCS and trauma center GCS was moderate for all patients (κ = 0.61, 95% confidence interval [CI] 0.57-0.64). Agreement was slightly better than chance alone in patients with trauma center GCS between 9 and 12 y (κ = 0.09, 95% CI 0.03-0.15) and was lower for children aged 0-2 y (κ = 0.51, 95% CI 0.42-0.61) than for those aged between 3 and 18 y (κ = 0.63, 95% CI 0.59-0.66). Younger children were more likely to have score differences of at least 3 points (21.3% versus 13.6% of 3- to 18-y-olds, P < 0.001). CONCLUSIONS: Prehospital and trauma center GCS scores frequently disagree in children, particularly in TBI patients aged <3 y and those with moderate TBI. Centers should consider the inconsistency of the pediatric GCS when triaging TBI patients.

Risk Factors for Mortality in Pediatric Postsurgical versus Medical Severe Sepsis.

BACKGROUND: Sepsis is a leading cause of morbidity and mortality after surgery. Most studies regarding sepsis do not differentiate between patients who have had recent surgery and those without. Few data exist regarding the risk factors for poor outcomes in pediatric postsurgical sepsis. Our hypothesis is pediatric postsurgical, and medical patients with severe sepsis have unique risk factors for mortality. METHODS: Data were extracted from a secondary analysis of an international point prevalence study of pediatric severe sepsis. Sites included 128 pediatric intensive care units from 26 countries. Pediatric patients with severe sepsis were categorized into those who had recent surgery (postsurgical sepsis) versus those that did not (medical sepsis) before sepsis onset. Multivariable logistic regression models were used to determine risk factors for mortality. RESULTS: A total of 556 patients were included: 138 with postsurgical and 418 with medical sepsis. In postsurgical sepsis, older age, admission from the hospital ward, multiple organ dysfunction syndrome at sepsis recognition, and cardiovascular and respiratory comorbidities were independent risk factors for death. In medical sepsis, resource-limited region, hospital-acquired infection, multiple organ dysfunction syndrome at sepsis recognition, higher Pediatric Index of Mortality-3 score, and malignancy were independent risk factors for death. CONCLUSIONS: Pediatric patients with postsurgical sepsis had different risk factors for mortality compared with medical sepsis. This included a higher mortality risk in postsurgical patients presenting to the intensive care unit from the hospital ward. These data suggest an opportunity to develop and test early warning systems specific to pediatric sepsis in the postsurgical population.

Management and outcomes of peripancreatic fluid collections and pseudocysts following non-operative management of pancreatic injuries in children.

BACKGROUND: Peripancreatic fluid collection and pseudocyst development is a common sequela following non-operative management (NOM) of pancreatic injuries in children. Our purpose was to review management strategies and assess outcomes. METHODS: A multicenter, retrospective review was conducted of children treated with NOM following blunt pancreatic injury at 22 pediatric trauma centers between the years 2010 and 2015. Organized fluid collections were called "acute peripancreatic fluid collection" (APFC) if identified < 4 weeks and "pseudocyst" if > 4 weeks following injury. Data analysis included descriptive statistics Wilcoxon rank-sum, Kruskal-Wallis and t tests. RESULTS: One hundred patients with blunt pancreatic injury were identified. Median age was 8.5 years (range 1-16). Forty-two percent of patients (42/100) developed organized fluid collections: APFC 64% (27/42) and pseudocysts 36% (15/42). Median time to identification was 12 days (range 7-42). Most collections (64%, 27/42) were observed and 36% (15/42) underwent drainage: 67% (10/15) percutaneous drain, 7% (1/15) needle aspiration, and 27% (4/15) endoscopic transpapillary stent. A definitive procedure (cystogastrostomy/pancreatectomy) was required in 26% (11/42). Patients with larger collections (≥ 7.1 cm) had longer time to resolution. Comparison of outcomes in patients with observation vs drainage revealed no significant differences in TPN use (79% vs 75%, p = 1.00), hospital length of stay (15 vs 25 median days, p = 0.11), time to tolerate regular diet (12 vs 11 median days, p = 0.47), or need for definitive procedure (failure rate 30% vs 20%, p = 0.75). CONCLUSIONS: Following NOM of blunt pancreatic injuries in children, organized fluid collections commonly develop. If discovered early, most can be observed successfully, and drainage does not appear to improve clinical outcomes. Larger size predicts prolonged recovery. LEVEL OF EVIDENCE: III STUDY TYPE: Case series.

Abnormal lymphocyte response after pediatric thermal injury is associated with adverse outcomes.

BACKGROUND: Burns are a leading cause of morbidity in children, with infections representing the most common group of complications. Severe thermal injuries are associated with a profound inflammatory response, but the utility of laboratory values to predict infections in pediatric burn patients is poorly understood. MATERIALS AND METHODS: Our institutional burn database was queried for patients aged 18 y and younger with at least 10% total body surface area burns. Demographics, mechanism, laboratory results, and outcomes were extracted from the medical record. Patients were classified as having an abnormal or normal total white blood cell count, neutrophil percentage, and lymphocyte percentage using the first complete blood count drawn 72 or more hours postinjury. Outcomes were compared between groups. RESULTS: White blood cell data were available for 90 patients, 84 of whom had neutrophil and lymphocyte percentages. Abnormal lymphocyte percentage 72 h or more after burn injury was associated with a significant increase in infections (67.9% versus 32.3%, P = 0.003), length of stay (33.1 versus 18.8 d, P = 0.02), intensive care unit length of stay (13.1 versus 3.7 days, P = 0.01), and ventilator days (5.8 versus 2.3, P = 0.02). It was also an independent predictor of infection (odds ratio 7.2, 95% confidence interval 2.1-24.5). CONCLUSIONS: Abnormal lymphocyte percentage at or after 72 h after burn injury is associated with adverse outcomes, including increased infectious risk.

Comparison of the Lund and Browder table to computed tomography scan three-dimensional surface area measurement for a pediatric cohort.

BACKGROUND: Treating burns effectively requires accurately assessing the percentage of the total body surface area (%TBSA) affected by burns. Current methods for estimating %TBSA, such as Lund and Browder (L&B) tables, rely on historic body statistics. An increasingly obese population has been blamed for increasing errors in %TBSA estimates. However, this assumption has not been experimentally validated. We hypothesized that errors in %TBSA estimates using L&B were due to differences in the physical proportions of today's children compared with children in the early 1940s when the chart was developed and that these differences would appear as body mass index (BMI)-associated systematic errors in the L&B values versus actual body surface areas. MATERIALS AND METHODS: We measured the TBSA of human pediatric cadavers using computed tomography scans. Subjects ranged from 9 mo to 15 y in age. We chose outliers of the BMI distribution (from the 31st percentile at the low through the 99th percentile at the high). We examined surface area proportions corresponding to L&B regions. RESULTS: Measured regional proportions based on computed tomography scans were in reasonable agreement with L&B, even with subjects in the tails of the BMI range. The largest deviation was 3.4%, significantly less than the error seen in real-world %TBSA estimates. CONCLUSIONS: While today's population is more obese than those studied by L&B, their body region proportions scale surprisingly well. The primary error in %TBSA estimation is not due to changing physical proportions of today's children and may instead lie in the application of the L&B table.

Comparison of diagnostic imaging modalities for the evaluation of pancreatic duct injury in children: a multi-institutional analysis from the Pancreatic Trauma Study Group.

PURPOSE: Determining the integrity of the pancreatic duct is important in high-grade pancreatic trauma to guide decision making for operative vs non-operative management. Computed tomography (CT) is generally an inadequate study for this purpose, and magnetic resonance cholangiopancreatography (MRCP) is sometimes obtained to gain additional information regarding the duct. The purpose of this multi-institutional study was to directly compare the results from CT and MRCP for evaluating pancreatic duct disruption in children with these rare injuries. METHODS: Retrospective study of data obtained from eleven pediatric trauma centers from 2010 to 2015. Children up to age 18 with suspected blunt pancreatic duct injury who had both CT and MRCP within 1 week of injury were included. Imaging findings of both studies were directly compared and analyzed using descriptive statistics, Chi square, Wilcoxon rank-sum, and McNemar's tests. RESULTS: Data were collected for 21 patients (mean age 7.8 years). The duct was visualized more often on MRCP than CT (48 vs 5%, p < 0.05). Duct disruption was confirmed more often on MRCP than CT (24 vs 0%), suspected based on secondary findings equally (38 vs 38%), and more often indeterminate on CT (62 vs 38%). Overall, MRCP was not superior to CT for determining duct integrity (62 vs 38%, p = 0.28). CONCLUSIONS: In children with blunt pancreatic injury, MRCP is more useful than CT for identifying the pancreatic duct but may not be superior for confirmation of duct integrity. Endoscopic retrograde cholangiogram (ERCP) may be necessary to confirm duct disruption when considering pancreatic resection. LEVEL OF EVIDENCE: III.

Inflammation and innate immune function in critical illness.

PURPOSE OF REVIEW: The purpose of review is to highlight the inflammatory response in critical illness and the importance of immune monitoring and modulation in the diagnosis and treatment of critical illness-induced innate immune suppression. RECENT FINDINGS: The pro and anti-inflammatory responses are known to be concurrently activated in many patients requiring intensive care, with innate immune suppression emerging as an important, and potentially reversible, complication of critical illness. SUMMARY: The initial inflammatory response to critical illness is typically driven by innate immune cells, including neutrophils, monocytes, and macrophages. The proinflammatory mediators made by these cells are responsible for many of the pathophysiologic features of critical illness. Concurrent with this, however, is a compensatory anti-inflammatory response, including the elaboration of anti-inflammatory mediators and impairment of innate immune cell function. This includes reduction of monocyte human leukocyte antigen-DR expression and impairment of the ability of innate immune cells to produce tumor necrosis factor alpha when stimulated ex vivo. In its most severe form this is referred to as immunoparalysis, and is associated with markedly increased risks for secondary infection and death in the ICU. Prospective testing can detect this phenomenon, and immunostimulatory strategies, including the use of granulocyte macrophage-colony stimulating factor, have the potential to restore innate immune function in this setting.

Update on bariatric surgery in adolescence.

PURPOSE OF REVIEW: Recent evidence highlighting the prevalence of severe obesity in the pediatric population, coupled with disappointing outcomes related to medical weight loss interventions, has led to increased interest in bariatric surgery. This article focuses on recent additions to the literature regarding the current indications and outcomes of adolescent bariatric surgery, emerging guidelines on the development of surgical weight loss programs and the status of access to bariatric surgical care for adolescents in the United States. RECENT FINDINGS: Current data have shown a steady rise in the use of bariatric surgery among adolescents and serve to highlight the prevalence of several important obesity-related comorbidities. In addition to reports showing the safety and efficacy of adolescent bariatric surgery, a number of investigators have demonstrated significant improvement in key physiological and metabolic parameters (i.e., glucose metabolism, elevated blood pressure, dyslipidemia, etc.), offering updated consensus-driven guidelines for the indications for surgical intervention, as well as the development of multidisciplinary adolescent-specific care. Despite favorable outcomes, a disparity exists between the pediatric and adult populations related to access to such care. SUMMARY: In contrast to previous small and mostly retrospective series, contemporary studies have shown that adolescent bariatric surgery is well tolerated and effective. Despite these findings and the emergence of a national consensus regarding multidisciplinary care, skepticism among primary care providers, as well as significant challenges related to healthcare access, remain. Longitudinal studies and open dialogue within the medical community are needed.

Development and implementation of an electronic health record generated surgical handoff and rounding tool.

Electronic health records (EHR) have been adopted across the nation at tremendous effort and expense. The purpose of this study was to assess improvements in accuracy, efficiency, and patient safety for a high-volume pediatric surgical service with adoption of an EHR-generated handoff and rounding list. The quality and quantity of errors were compared pre- and post-EHR-based list implementation. A survey was used to determine time spent by team members using the two versions of the list. Perceived utility, safety, and quality of the list were reported. Serious safety events determined by the hospital were also compared for the two periods. The EHR-based list eliminated clerical errors while improving efficiency by automatically providing data such as vital signs. Survey respondents reported 43 min saved per week per team member, translating to 372 work hours of time saved annually for a single service. EHR-based list users reported higher satisfaction and perceived improvement in efficiency, accuracy, and safety. Serious safety events remained unchanged. In conclusion, creation of an EHR-based list to assist with daily handoffs, rounding, and patient management demonstrated improved accuracy, increased efficiency, and assisted in maintaining a high level of safety.

Neutrophil-endothelial interactions mediate angiopoietin-2-associated pulmonary endothelial cell dysfunction in indirect acute lung injury in mice.

Unresolved inflammation in the lung is thought to elicit loss of endothelial cell (EC) barrier integrity and impaired lung function. We have shown, in a mouse model of shock/sepsis, that neutrophil interactions with resident pulmonary cells appear central to the pathogenesis of indirect acute lung injury (iALI). Normally, EC growth factors angiopoietin (Ang)-1 and Ang-2 maintain vascular homeostasis through tightly regulated interaction with the kinase receptor Tie2 expressed on ECs. Although Ang-1/Tie2 has been shown to promote vessel integrity, stimulating downstream prosurvival/antiinflammatory signaling, Ang-2, released from activated ECs, is reported to promote vessel destabilization. This mechanism of regulation, together with recent clinical findings that plasma Ang-2 levels are significantly elevated in patients who develop acute respiratory distress syndrome, has focused our investigation on the contribution of Ang-2 to the development of iALI. A murine model of hemorrhagic shock-induced priming for the development of iALI after subsequent septic challenge was used in this study. Our findings show that 1) Ang-2 is elevated in our experimental model for iALI, 2) direct EC/neutrophil interactions contribute significantly to EC Ang-2 release, and 3) suppression of Ang-2 significantly decreases inflammatory lung injury, neutrophil influx, and lung and plasma IL-6 and TNF-α. These findings support our hypothesis and suggest that Ang-2 plays a role in the loss of pulmonary EC barrier function in the development of iALI in mice resultant from the sequential insults of hemorrhagic shock and sepsis and that this is mediated by EC interaction with activated neutrophils.

Impact of laser treatment on hypertrophic burn scars in pediatric burn patients.

Paediatric patients with hypertrophic burn scars benefit from laser treatment, but this treatment's effectiveness on burn wounds stratified by specific body region and prior burn wound therapy has not been fully evaluated. We performed a single center retrospective study of pediatric burn patients, treated with fractional CO2, with or without pulse dye, laser between 2018-2022. We identified 99 patients treated with 332 laser sessions. Median age at the time of burn injury was 4.0 years (IQR 1.7, 10.0) and 7.1 years (IQR 3.6, 12.2) at the time of first laser treatment. In the acute setting, 55.2 % were treated with dermal substrate followed by autografting, 29.6 % were treated with dermal substrate alone, and 9.1 % underwent autografting alone. Most body regions showed improvement in modified Vancouver Scar Scale (mVSS) score with laser treatment. mVSS scores improved significantly with treatment to the anterior trunk (-1.18, p = 0.01), arms (-1.14, p = 0.003), and legs (-1.17, p = 0.015). Averaging all body regions, the mVSS components of pigmentation (-0.34, p < 0.001) and vascularity (-0.47, p < 0.001), as well as total score (-0.81, p < 0.001) improved significantly. Knowing the variable effectiveness of laser treatment in pediatric burn scars is useful in counseling patients and families pre-treatment.

FAS(APO), DAMP, and AKT Phosphoproteins Expression Predict the Development of Nosocomial Infection After Pediatric Burn Injury.

Pediatric burn injuries are a leading cause of morbidity with infections being the most common acute complication. Thermal injuries elicit a heightened cytokine response while suppressing immune function; however, the mechanisms leading to this dysfunction are still unknown. Our aim was to identify extracellular proteins and circulating phosphoprotein expression in the plasma after burn injury to predict the development of nosocomial infection (NI). Plasma was collected within 72 hours after injury from sixty-four pediatric burn subjects; of these, eighteen went on to develop a NI. Extracellular damage associated molecular proteins (DAMPs), FAS(APO), and protein kinase b (AKT) signaling phosphoproteins were analyzed. Subjects who went on to develop a NI had elevated high mobility group box 1 (HMGB1), heat shock protein 90 (HSP90), and FAS expression than those who did not develop a NI after injury (NoNI). Concurrently, phosphorylated (p-) AKT and mammalian target of rapamycin (p-mTOR) were elevated in those subjects who went on to develop a NI. Quadratic discriminant analysis revealed distinct differential profiles between NI and NoNI burn subjects using HSP90, FAS, and p-mTOR. The area under the receiver-operator characteristic curves displayed significant ability to distinguish between these two burn subject cohorts. These findings provide insight into predicting the signaling proteins involved in the development of NI in pediatric burn patients. Further these proteins show promise as a diagnostic tool for pediatric burn patients at risk of developing infection while additional investigation may lead to potential therapeutics to prevent NI.

ALTERED PROFILES OF EXTRACELLULAR MITOCHONDRIAL DNA IN IMMUNOPARALYZED PEDIATRIC PATIENTS AFTER THERMAL INJURY.

ABSTRACT: Background: Thermal injury is a major cause of morbidity and mortality in the pediatric population worldwide with secondary infection being the most common acute complication. Suppression of innate and adaptive immune function is predictive of infection in pediatric burn patients, but little is known about the mechanisms causing these effects. Circulating mitochondrial DNA (mtDNA), which induces a proinflammatory signal, has been described in multiple disease states but has not been studied in pediatric burn injuries. This study examined the quantity of circulating mtDNA and mtDNA mutations in immunocompetent (IC) and immunoparalyzed (IP) pediatric burn patients. Methods: Circulating DNA was isolated from plasma of pediatric burn patients treated at Nationwide Children's Hospital Burn Center at early (1-3 days) and late (4-7 days) time points postinjury. These patients were categorized as IP or IC based on previously established immune function testing and secondary infection. Three mitochondrial genes, D loop, ND1, and ND4, were quantified by multiplexed qPCR to assess both mtDNA quantity and mutation load. Results: At the early time point, there were no differences in plasma mtDNA quantity; however, IC patients had a progressive increase in mtDNA over time when compared with IP patients (change in ND1 copy number over time 3,880 vs. 87 copies/day, P = 0.0004). Conversely, the IP group had an increase in mtDNA mutation burden over time. Conclusion: IC patients experienced a significant increase in circulating mtDNA quantity over time, demonstrating an association between increased mtDNA release and proinflammatory phenotype in the burn patients. IP patients had significant increases in mtDNA mutation load likely representative of degree of oxidative damage. Together, these data provide further insight into the inflammatory and immunological mechanisms after pediatric thermal injury.