Multiplexed Human Gene Expression Analysis Reveals a Central Role of the TLR/mTOR/PPARγ and NFkB Axes in Burn and Inhalation Injury-Induced Changes in Systemic Immunometabolism and Long-Term Patient Outcomes.

Burn patients are subject to significant acute immune and metabolic dysfunction. Concomitant inhalation injury increases mortality by 20%. In order to identify specific immune and metabolic signaling pathways in burn (B), inhalation (I), and combined burn-inhalation (BI) injury, unbiased nanoString multiplex technology was used to investigate gene expression within peripheral blood mononuclear cells (PBMCs) from burn patients, with and without inhalation injury. PBMCs were collected from 36 injured patients and 12 healthy, non-burned controls within 72 h of injury. mRNA was isolated and hybridized with probes for 1342 genes related to general immunology and cellular metabolism. From these specific gene patterns, specific cellular perturbations and signaling pathways were inferred using robust bioinformatic tools. In both B and BI injuries, elements of mTOR, PPARγ, TLR, and NF-kB signaling pathways were significantly altered within PBMC after injury compared to PBMC from the healthy control group. Using linear regression modeling, (1) DEPTOR, LAMTOR5, PPARγ, and RPTOR significantly correlated with patient BMI; (2) RPTOR significantly correlated with patient length of stay, and (3) MRC1 significantly correlated with the eventual risk of patient mortality. Identification of mediators of this immunometabolic response that can act as biomarkers and/or therapeutic targets could ultimately aid the management of burn patients.

Characterization of the Basal and mTOR-Dependent Acute Pulmonary and Systemic Immune Response in a Murine Model of Combined Burn and Inhalation Injury.

Severe burn injury leads to a cascade of local and systemic immune responses that trigger an extreme state of immune dysfunction, leaving the patient highly susceptible to acute and chronic infection. When combined with inhalation injury, burn patients have higher mortality and a greater chance of developing secondary respiratory complications including infection. No animal model of combined burn and inhalation injury (B+I) exists that accurately mirrors the human clinical picture, nor are there any effective immunotherapies or predictive models of the risk of immune dysfunction. Our earlier work showed that the mechanistic/mammalian target of rapamycin (mTOR) pathway is activated early after burn injury, and its chemical blockade at injury reduced subsequent chronic bacterial susceptibility. It is unclear if mTOR plays a role in the exacerbated immune dysfunction seen after B+I injury. We aimed to: (1) characterize a novel murine model of B+I injury, and (2) investigate the role of mTOR in the immune response after B+I injury. Pulmonary and systemic immune responses to B+I were characterized in the absence or presence of mTOR inhibition at the time of injury. Data describe a murine model of B+I with inhalation-specific immune phenotypes and implicate mTOR in the acute immune dysfunction observed.

Pseudomonas aeruginosa exoproducts determine antibiotic efficacy against Staphylococcus aureus.

Chronic coinfections of Staphylococcus aureus and Pseudomonas aeruginosa frequently fail to respond to antibiotic treatment, leading to significant patient morbidity and mortality. Currently, the impact of interspecies interaction on S. aureus antibiotic susceptibility remains poorly understood. In this study, we utilize a panel of P. aeruginosa burn wound and cystic fibrosis (CF) lung isolates to demonstrate that P. aeruginosa alters S. aureus susceptibility to bactericidal antibiotics in a variable, strain-dependent manner and further identify 3 independent interactions responsible for antagonizing or potentiating antibiotic activity against S. aureus. We find that P. aeruginosa LasA endopeptidase potentiates lysis of S. aureus by vancomycin, rhamnolipids facilitate proton-motive force-independent tobramycin uptake, and 2-heptyl-4-hydroxyquinoline N-oxide (HQNO) induces multidrug tolerance in S. aureus through respiratory inhibition and reduction of cellular ATP. We find that the production of each of these factors varies between clinical isolates and corresponds to the capacity of each isolate to alter S. aureus antibiotic susceptibility. Furthermore, we demonstrate that vancomycin treatment of a S. aureus mouse burn infection is potentiated by the presence of a LasA-producing P. aeruginosa population. These findings demonstrate that antibiotic susceptibility is complex and dependent not only upon the genotype of the pathogen being targeted, but also on interactions with other microorganisms in the infection environment. Consideration of these interactions will improve the treatment of polymicrobial infections.

Lipopolysaccharide Potentiates Insulin-Driven Hypoglycemic Shock.

Critically ill patients typically present with hyperglycemia. Treatment with conventional insulin therapy (targeting 144-180 mg/dl) improves patient survival; however, intensive insulin therapy (IIT) targeting normal blood glucose levels (81-108 mg/dl) increases the incidence of moderate and severe hypoglycemia, and increases mortality. Septic patients are especially prone to IIT-induced hypoglycemia, but the mechanism remains unknown. Here, we show that codelivery of insulin with otherwise sublethal doses of LPS induced hypoglycemic shock in mice within 1-2 h. LPS impaired clearance of insulin, which amplified insulin receptor signaling. These effects were mediated by caspase-11, TLR4, and complement, each of which trigger eicosanoid production that potentiates insulin signaling. Finally, in an animal model of sepsis, we observed that Salmonella typhimurium-infected mice exhibited simultaneous impaired insulin clearance coexisting with insulin resistance. Our results raise the possibility that septic patients have impaired insulin clearance, which could increase their susceptibility to hypoglycemia during IIT, contraindicating its use.

Innate Immune Cell Recovery Is Positively Regulated by NLRP12 during Emergency Hematopoiesis.

With enhanced concerns of terrorist attacks, dual exposure to radiation and thermal combined injury (RCI) has become a real threat with devastating immunosuppression. NLRP12, a member of the NOD-like receptor family, is expressed in myeloid and bone marrow cells and was implicated as a checkpoint regulator of inflammatory cytokines, as well as an inflammasome activator. We show that NLRP12 has a profound impact on hematopoietic recovery during RCI by serving as a checkpoint of TNF signaling and preventing hematopoietic apoptosis. Using a mouse model of RCI, increased NLRP12 expression was detected in target tissues. Nlrp12-/- mice exhibited significantly greater mortality, an inability to fight bacterial infection, heightened levels of proinflammatory cytokines, overt granulocyte/monocyte progenitor cell apoptosis, and failure to reconstitute peripheral myeloid populations. Anti-TNF Ab administration improved peripheral immune recovery. These data suggest that NLRP12 is essential for survival after RCI by regulating myelopoiesis and immune reconstitution.

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.

Blocking CXCL1-dependent neutrophil recruitment prevents immune damage and reduces pulmonary bacterial infection after inhalation injury.

Smoke inhalation associated with structural fires, wildfires, or explosions leads to lung injury, for which innovative and clinically relevant animal models are needed to develop effective therapeutics. We have previously reported that damage-associated molecular patterns (DAMPs) and anti-inflammatory cytokines correlate with infectious complications in patients diagnosed with inhalational injury. In this study, we describe a novel and translational murine model of acute inhalational injury characterized by an accumulation of protein and neutrophils in the bronchoalveolar space, as well as histological evidence of tissue damage. Mice were anesthetized, and a cannula was placed in the trachea and exposed to smoldering plywood smoke three times for 2-min intervals in a smoke chamber. Here we demonstrate that this model recapitulates clinically relevant phenotypes, including early release of double-stranded DNA (dsDNA), IL-10, monocyte chemoattractant protein (MCP)-1, and CXCL1 along with neutrophilia early after injury, accompanied by subsequent susceptibility to opportunistic infection with Pseudomonas aeruginosa. Further investigation of the model, and in turn a reanalysis of patient samples, revealed a late release of the DAMP hyaluronic acid (HA) from the lung. Using nitric oxide synthase-deficient mice, we found that Nos2 was required for increases in IL-10, MCP-1, and HA following injury but not release of dsDNA, CXCL1 expression, early neutrophilia, or susceptibility to opportunistic infection. Depletion of CXCL1 attenuated early neutrophil recruitment, leading to decreased histopathology scores and improved bacterial clearance in this model of smoke inhalation. Together, these data highlight the potential therapeutic benefit of attenuating neutrophil recruitment in the first 24 h after injury in patients.

Postoperative outcomes of esophagectomy for cancer in elderly patients.

BACKGROUND: The number of elderly patients with esophageal cancer is expected to increase. We aimed to determine the postoperative outcomes of esophagectomy for esophageal cancer in elderly patients. MATERIAL AND METHODS: A retrospective, population-based analysis was performed using the National inpatient sample for the period 2000-2014. Adult patients ≥18 years old (yo) diagnosed with esophageal cancer who underwent esophagectomy during their inpatient hospitalization were included. Patients were categorized into <70 yo and ≥70 yo. Multivariable linear and logistic regressions were used to assess the potential effect of age on postoperative complications, inpatient mortality, and hospital charges. RESULTS: Overall, 5243 patients were included, with 3699 (70.6%) <70 yo and 1544 (29.5%) ≥70 yo. The yearly rate of esophagectomies among patients ≥70 yo did not significantly changed during the study period (28.4% in 2000 and 26.3% in 2014, P = 0.76). Elderly patients were significantly more likely to have postoperative cardiac failure (odds ratio 1.59, 95% confidence interval [CI] 1.21, 2.09, P = 0.0009) and inpatient mortality (odds ratio 1.84, 95% CI 1.39, 2.45, P < 0.0001). Among the elderly patients, hospital charges were, on average, $16,320 greater (95% CI $3110, $29,530) than patients <70 yo (P = 0.02). The predicted probability of mortality increased consistently across age (1.5% in 40 yo, 2.5% in 50 yo, 3.6% in 60 yo, 5.4% in 70 yo, and 7.0% in 80 yo). CONCLUSIONS: Elderly patients undergoing esophagectomy for cancer have a significantly higher risk of postoperative mortality and pose a higher financial burden on the health care system. Elderly patients with esophageal cancer should be carefully selected for surgery.

Colonization with Multidrug-Resistant Enterobacteriaceae is Associated with Increased Mortality Following Burn Injury in Sub-Saharan Africa.

BACKGROUND: Multidrug-resistant (MDR) bacteria are an emerging international concern in low- and middle-income countries that threaten recent public health gains. These challenges are exacerbated in immunocompromised hosts, such as those with burn injury. This study sought to describe the epidemiology and associated clinical outcomes of burn wound colonization in a Malawian tertiary burn center. METHODS: This is a prospective analysis of burn patients presenting to Kamuzu Central Hospital in Lilongwe, Malawi, within 72 h of burn injury. A swab of each patient's primary wound was collected at admission and each subsequent week. The primary exposure was burn wound colonization with MDR bacteria, particularly Enterobacteriaceae. The primary outcome was in-hospital mortality. A log binomial model estimated the association between the exposure and outcome, adjusted for confounders. RESULTS: Ninety-nine patients were enrolled with a median age of 4 years (IQR 2-12) and a male preponderance (54%). Median total body surface area burn (TBSA) was 14% (IQR 9-25), and crude in-hospital mortality was 19%. Enterobacteriaceae were the most common MDR bacteria with 36% of patients becoming colonized. Wound colonization with MDR Enterobacteriaceae was associated with increased in-hospital mortality with a risk ratio of 1.86 (95% CI 1.38, 2.50, p < 0.001) adjusted for TBSA, burn type (scald vs. flame), sex, age, length of stay, and methicillin-resistant Staphylococcus aureus colonization. CONCLUSION: MDR bacteria, especially Enterobacteriaceae, are common and are associated with worse burn injury outcomes. In resource-poor environments, a greater emphasis on prevention of MDR bacterial colonization, improved isolation precautions, affordable diagnostics, and antibiotic stewardship are imperative.

Bacterial Infections After Burn Injuries: Impact of Multidrug Resistance.

Patients who are admitted to the hospital after sustaining a large burn injury are at high risk for developing hospital-associated infections. If patients survive the initial 72 hours after a burn injury, infections are the most common cause of death. Ventilator-associated pneumonia is the most important infection in this patient population. The risk of infections caused by multidrug-resistant bacterial pathogens increases with hospital length of stay in burn patients. In the first days of the postburn hospitalization, more susceptible, Gram-positive organisms predominate, whereas later more resistant Gram-negative organisms are found. These findings impact the choice of empiric antibiotics in critically ill burn patients. A proactive infection control approach is essential in burn units. Furthermore, a multidisciplinary approach to burn patients with a team that includes an infectious disease specialist and a pharmacist in addition to the burn surgeon is highly recommended.

A Prolonged Outbreak of KPC-3-Producing Enterobacter cloacae and Klebsiella pneumoniae Driven by Multiple Mechanisms of Resistance Transmission at a Large Academic Burn Center.

Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacter cloacae has been recently recognized in the United States. Whole-genome sequencing (WGS) has become a useful tool for analysis of outbreaks and for determining transmission networks of multidrug-resistant organisms in health care settings, including carbapenem-resistant Enterobacteriaceae (CRE). We experienced a prolonged outbreak of CRE E. cloacae and K. pneumoniae over a 3-year period at a large academic burn center despite rigorous infection control measures. To understand the molecular mechanisms that sustained this outbreak, we investigated the CRE outbreak isolates by using WGS. Twenty-two clinical isolates of CRE, including E. cloacae (n = 15) and K. pneumoniae (n = 7), were sequenced and analyzed genetically. WGS revealed that this outbreak, which seemed epidemiologically unlinked, was in fact genetically linked over a prolonged period. Multiple mechanisms were found to account for the ongoing outbreak of KPC-3-producing E. cloacae and K. pneumoniae This outbreak was primarily maintained by a clonal expansion of E. cloacae sequence type 114 (ST114) with distribution of multiple resistance determinants. Plasmid and transposon analyses suggested that the majority of blaKPC-3 was transmitted via an identical Tn4401b element on part of a common plasmid. WGS analysis demonstrated complex transmission dynamics within the burn center at levels of the strain and/or plasmid in association with a transposon, highlighting the versatility of KPC-producing Enterobacteriaceae in their ability to utilize multiple modes to resistance gene propagation.

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.

Injury Characteristics and Outcomes in Elderly Trauma Patients in Sub-Saharan Africa.

BACKGROUND: Traumatic injury in the elderly is an emerging global problem with an associated increase in morbidity and mortality. This study sought to describe the epidemiology of elderly injury and outcomes in sub-Saharan Africa. METHODS: We conducted a retrospective analysis of adult patients (≥ 18 years) with traumatic injuries presenting to the Kamuzu Central Hospital (KCH) in Lilongwe, Malawi, over 5 years (2009-2013). Elderly patients were defined as adults aged ≥65 years and compared to adults aged 18-44 and 45-64 years. We used propensity score matching and logistic regression to compare the odds of mortality between age groups using the youngest age group as the reference. RESULTS: 42,816 Adult patients with traumatic injuries presented to KCH during the study period. 1253 patients (2.9 %) were aged ≥65 years with a male preponderance (77.4 %). Injuries occurred more often at home as age increased (25.3, 29.5, 41.1 %, p < 0.001) and falls were more common (14.1, 23.8, 36.3 %, p < 0.001) for elderly patients. Elderly age was associated with a higher proportion of hospital admissions (10.6, 21.3, 35.2 %, p < 0.001). Upon propensity score matching and logistic regression analysis, the odds ratio of mortality for patients aged ≥65 was 3.15 (95 % CI 1.45, 6.82, p = 0.0037) compared to the youngest age group (18-44 years). CONCLUSIONS: Elderly trauma in a resource-poor area in sub-Saharan Africa is associated with a significant increase in hospital admissions and mortality. Significant improvements in trauma systems, pre-hospital care, and hospital capacity for older, critically ill patients are imperative.

Association between early airway damage-associated molecular patterns and subsequent bacterial infection in patients with inhalational and burn injury.

Bacterial infection is a major cause of morbidity affecting outcome following burn and inhalation injury. While experimental burn and inhalation injury animal models have suggested that mediators of cell damage and inflammation increase the risk of infection, few studies have been done on humans. This is a prospective, observational study of patients admitted to the North Carolina Jaycee Burn Center at the University of North Carolina who were intubated and on mechanical ventilation for treatment of burn and inhalational injury. Subjects were enrolled over a 2-yr period and followed till discharge or death. Serial bronchial washings from clinically indicated bronchoscopies were collected and analyzed for markers of tissue injury and inflammation. These include damage-associated molecular patterns (DAMPs) such as hyaluronic acid (HA), double-stranded DNA (dsDNA), heat-shock protein 70 (HSP-70), and high-mobility group protein B-1 (HMGB-1). The study population was comprised of 72 patients who had bacterial cultures obtained for clinical indications. Elevated HA, dsDNA, and IL-10 levels in bronchial washings obtained early (the first 72 h after injury) were significantly associated with positive bacterial respiratory cultures obtained during the first 14 days postinjury. Independent of initial inhalation injury severity and extent of surface burn, elevated levels of HA dsDNA and IL-10 in the central airways obtained early after injury are associated with subsequent positive bacterial respiratory cultures in patients intubated after acute burn/inhalation injury.

Next-Generation Sequencing and Comparative Analysis of Sequential Outbreaks Caused by Multidrug-Resistant Acinetobacter baumannii at a Large Academic Burn Center.

Next-generation sequencing (NGS) analysis has emerged as a promising molecular epidemiological method for investigating health care-associated outbreaks. Here, we used NGS to investigate a 3-year outbreak of multidrug-resistant Acinetobacter baumannii (MDRAB) at a large academic burn center. A reference genome from the index case was generated using de novo assembly of PacBio reads. Forty-six MDRAB isolates were analyzed by pulsed-field gel electrophoresis (PFGE) and sequenced using an Illumina platform. After mapping to the index case reference genome, four samples were excluded due to low coverage, leaving 42 samples for further analysis. Multilocus sequence types (MLST) and the presence of acquired resistance genes were also determined from the sequencing data. A transmission network was inferred from genomic and epidemiological data using a Bayesian framework. Based on single-nucleotide variant (SNV) differences, this MDRAB outbreak represented three sequential outbreaks caused by distinct clones. The first and second outbreaks were caused by sequence type 2 (ST2), while the third outbreak was caused by ST79. For the second outbreak, the MLST and PFGE results were discordant. However, NGS-based SNV typing detected a recombination event and consequently enabled a more accurate phylogenetic analysis. The distribution of resistance genes varied among the three outbreaks. The first- and second-outbreak strains possessed a blaOXA-23-like group, while the third-outbreak strains harbored a blaOXA-40-like group. NGS-based analysis demonstrated the superior resolution of outbreak transmission networks for MDRAB and provided insight into the mechanisms of strain diversification between sequential outbreaks through recombination.

A noninvasive hemoglobin monitor in the pediatric intensive care unit.

BACKGROUND: Critically ill pediatric patients frequently require hemoglobin monitoring. Accurate noninvasive Hb (SpHb) would allow practitioners to decrease anemia from repeated blood draws, traumatic blood draws, and a decreased number of laboratory Hb (LabHb) medical tests. The Food and Drug Administration has approved the Masimo Pronto SpHb and associated Rainbow probes; however, its use in the pediatric intensive care unit (PICU) is controversial. In this study, we define the degree of agreement between LabHb and SpHb using the Masimo Pronto SpHb Monitor and identify clinical and demographic conditions associated with decreased accuracy. MATERIALS AND METHODS: We performed a prospective, observational study in a large PICU at an academic medical center. Fifty-three pediatric patients (30-d and 18-y-old), weighing >3 kg, admitted to the PICU from January-April 2013 were examined. SpHb levels measured at the time of LabHb blood draw were compared and analyzed. RESULTS: Only 83 SpHb readings were obtained in 118 attempts (70.3%) and 35 readings provided a result of "unable to obtain." The mean LabHb and SpHb were 11.1 g/dL and 11.2 g/dL, respectively. Bland-Altman analysis showed a mean difference of 0.07 g/dL with a standard deviation of ±2.59 g/dL. Pearson correlation is 0.55, with a 95% confidence interval between 0.38 and 0.68. Logistic regression showed that extreme LabHb values, increasing skin pigmentation, and increasing body mass index were predictors of poor agreement between SpHb and LabHb (P < 0.05). Separately, increasing body mass index, hypoxia, and hypothermia were predictors for undetectable readings (P < 0.05). CONCLUSIONS: The Masimo Pronto SpHb Monitor provides adequate agreement for the trending of hemoglobin levels in critically ill pediatric patients. However, the degree of agreement is insufficient to be used as the sole indicator for transfusion decisions and should be used in context of other clinical parameters to determine the need for LabHb in critically ill pediatric patients.

Laser resurfacing and remodeling of hypertrophic burn scars: the results of a large, prospective, before-after cohort study, with long-term follow-up.

OBJECTIVES: Hypertrophic burn scars produce significant morbidity, including itching, pain, stiffness, and contracture, but best management practices remain unclear. We present the largest study to date that examines long-term impact of laser therapies, a potentially transformative technology, on scar remodeling. METHODS: We conducted a prospective, before-after cohort study in burn patients with hypertrophic scars. Pulsed-dye laser was used for pruritus and erythema; fractional CO2 laser was used for stiffness and abnormal texture. Outcomes included (1) Vancouver Scar Scale (VSS), which documents pigmentation, erythema, pliability, and height, and (2) University of North Carolina "4P" Scar Scale (UNC4P), which rates pain, pruritus, paresthesias, and pliability. RESULTS: A total of 147 burn patients (mean age, 26.9 years; total body surface area, 16.1%) received 415 laser sessions (2.8 sessions/patient), 16 months (median) after injury, including pulsed dye laser (n = 327) and CO2 (n = 139). Laser treatments produced rapid, significant, and lasting improvements in hypertrophic scar. Provider-rated VSS dropped from 10.43 [standard deviation (SD) 2.37] to 5.16 (SD 1.92), by the end of treatments, and subsequently decreased to 3.29 (SD 1.24), at a follow-up of 25 months. Patient-reported UNC4P fell from 5.40 (SD 2.54) to 2.05 (SD 1.67), after the first year, and further decreased to 1.74 (SD 1.72), by the end of the study period. CONCLUSIONS: For the first time, ever, in a large prospective study, laser therapies have been shown to dramatically improve both the signs and symptoms of hypertrophic burn scars, as measured by objective and subjective instruments. Laser treatment of burn scars represents a disruptive innovation that can yield results not previously possible and may displace traditional methods of operative intervention.

A systematic review of advance practice providers in acute care: options for a new model in a burn intensive care unit.

INTRODUCTION: Accreditation Council for Graduate Medical Education mandated work-hour restrictions have negatively impacted many areas of clinical care, including management of burn patients, who require intensive monitoring, resuscitation, and procedural interventions. As surgery residents become less available to meet service needs, new models integrating advanced practice providers (APPs) into the burn team must emerge. We performed a systematic review of APPs in critical care questioning, how best to use all providers to solve these workforce challenges? METHODS: We performed a systematic review of PubMed, CINAHL, Ovid, and Google Scholar, from 2002 to 2012, using the key words: nurse practitioner, physician assistant, critical care, and burn care. After applying inclusion/exclusion criteria, 18 relevant articles were selected for review. In addition, throughput and financial models were developed to examine provider staffing patterns. RESULTS: Advanced practice providers in critical care settings function in various models, both with and without residents, reporting to either an intensivist or an attending physician. When APPs participated, patient outcomes were similar or improved compared across provider models. Several studies reported considerable cost-savings due to decrease length of stay, decreased ventilator days, and fewer urinary tract infections when nurse practitioners were included in the provider mix. CONCLUSIONS: Restrictions in resident work-hours and changing health care environments require that new provider models be created for acute burn care. This article reviews current utilization of APPs in critical care units and proposes a new provider model for burn centers.

To heal and restore broken bodies: a retrospective, descriptive study of the role and impact of pastoral care in the treatment of patients with burn injury.

INTRODUCTION: Despite advances in resuscitation, resurfacing, and reconstruction, recovery in burn patients often depends upon emotional, psychosocial, and spiritual healing. We characterized the spiritual needs of burn patients to help identify resources necessary to optimize recovery. METHODS: We performed a retrospective review of all patients admitted to a regional, accredited burn center, in 2011. We accessed multiple clinical, financial, and administrative databases, collected demographic data, including religious affiliation, and recorded the number and type of pastoral care visits. Outcome measures included length of stay (LOS), physician and facility charges, and mortality. We compared patients who had a pastoral care visit with those who did not, as well as patients with a religious affiliation with those who had no or an unknown affiliation. RESULTS: During the study period, our burn center admitted 1338 patients, 314 of whom were visited by chaplains, for a total of 1077 encounters (3.43 visits per patient seen). Most frequent interventions were prayer, social support, and spiritual counseling. Compared to patients who had no visit, patients who saw a chaplain had a larger total body surface area burn, longer LOS, higher charges, and higher mortality (10.2% vs. 0.78%, P < 0.001). Patients who had a religious affiliation had slightly lower mortality than patients with unknown or no religious affiliation (0.87% vs. 3.19%), but this did not reach statistical significance. CONCLUSIONS: In burn patients, utilization of pastoral care appears to be linked to size of burn, financial charges, and length of stay, with religious affiliation serving as a possible marker for improved survival. Plastic surgeons and burn providers should consider and address the spiritual needs of burn patients, as a component of recovery.

Application of SIRS criteria to a paediatric surgical population in Malawi.

INTRODUCTION: Little is known regarding systemic inflammatory response syndrome (SIRS) criteria and mortality in developing countries. We evaluated the utility of the SIRS criteria to predict death among a paediatric surgical population in Lilongwe, Malawi. METHODS: Age, SIRS variables (temperature, heart rate, systolic blood pressure, respiratory rate and leucocyte count), diagnosis, surgical procedure and outcome were analysed for paediatric surgical patients during 2012. Age-specific criteria for SIRS variables were then applied to the data. RESULTS: Using published SIRS criteria, temperature was the only variable that correlated with mortality. When norms for an African population were used, leucocyte count also correlated with mortality. DISCUSSION: With the exception of temperature, published SIRS criteria were not predictive of mortality. Leucocyte count became predictive of death using norms specific to an African population. SIRS and its component data are a worthwhile area of future prospective research in developing countries.