Preliminary Exploration of Long-Term Patient Outcomes After Tracheostomy in Burns: A Burn Model System Study.

INTRODUCTION: Upper airway management is crucial to burn care. Endotracheal intubation is often performed in the setting of inhalation injury, burns of the face and neck, or large burns requiring significant resuscitation. Tracheostomy may be necessary in patients requiring prolonged ventilatory support. This study compares long-term, patient-reported outcomes in burn patients with and without tracheostomy. MATERIALS AND METHODS: Data from the Burn Model System Database, collected from 2013 to 2020, were analyzed. Demographic and clinical data were compared between those with and without tracheostomy. The following patient-reported outcomes, collected at 6-, 12-, and 24-mo follow-up, were analyzed: Veterans RAND 12-Item Health Survey (VR-12), Satisfaction with Life, Community Integration Questionnaire, Patient-Reported Outcomes Measurement Information System 29-Item Profile Measure, employment status, and days to return to work. Regression models and propensity-matched analyses were used to assess the associations between tracheostomy and each outcome. RESULTS: Of 714 patients included in this study, 5.5% received a tracheostomy. Mixed model regression analyses demonstrated that only VR-12 Physical Component Summary scores at 24-mo follow-up were significantly worse among those requiring tracheostomy. Tracheostomy was not associated with VR-12 Mental Component Summary, Satisfaction with Life, Community Integration Questionnaire, or Patient-Reported Outcomes Measurement Information System 29-Item Profile Measure scores. Likewise, tracheostomy was not found to be independently associated with employment status or days to return to work. CONCLUSIONS: This preliminary exploration suggests that physical and psychosocial recovery, as well as the ability to regain employment, are no worse in burn patients requiring tracheostomy. Future investigations of larger scale are still needed to assess center- and provider-level influences, as well as the influences of various hallmarks of injury severity. Nonetheless, this work should better inform goals of care discussions with patients and families regarding the use of tracheostomy in burn injury.

Experiences of Alaska Native people living with burn injury and opportunities for health system strengthening.

BACKGROUND: Injuries are a leading cause of death and disability for Alaska Native (AN) people. Alaska Native Tribal Health Consortium (ANTHC) is supporting the development of a burn care system that includes a partnership between Alaska Native Medical Center (ANMC) in Anchorage, AK and UW Medicine Regional Burn Center at Harborview Medical Center (HMC) in Seattle, WA. We aimed to better understand the experiences of AN people with burn injuries across the care continuum to aid development of culturally appropriate care regionalization. METHODS: We performed focus groups with twelve AN people with burn injury and their caregivers. A multidisciplinary team of burn care providers, qualitative research experts, AN care coordinator, and AN cultural liaison led focus groups to elicit experiences across the burn care continuum. Transcripts were analyzed using a phenomenological approach and inductive coding to understand how AN people and families navigated the medical and community systems for burn care and areas for improvement. RESULTS: Three themes were identified: 1-Challenges with local burn care in remote communities including limited first aid, triage, pain management, and wound care, as well as long-distance transport to definitive care; 2-Divergence between cultural values and medical practices that generated mistrust in the medical system, isolation from their support systems, and recovery goals that were not aligned with their needs; 3-Difficulty accessing emotional health support and a survivor community that could empower their resilience. CONCLUSION: Participants reported modifiable barriers to culturally competent treatment for burn injuries among AN people. The findings can inform initiatives that leverage existing resources, including expansion of the Extension for Community Healthcare Outcomes (ECHO) telementoring program, promulgation of the Phoenix Society Survivors Offering Assistance in Recovery (SOAR) to AK, coordination of regionalized care to reduce time away from AK and provide more comfortable community reintegration, and define rehabilitation goals in terms that align with personal goals and subsistence lifestyle skills. Long-distance transport times are non-modifiable, but better pre-hospital care could be achieved by harnessing existing telehealth services and adapting principles of prolonged field care to allow for triage, initial care, and resuscitation in remote environments.

Correlation Between the Warrior/Worrier Gene on Post Burn Pruritus and Scarring: A Prospective Cohort Study.

INTRODUCTION: Associations between genetic variation and clinical conditions suggest that single nucleotide polymorphisms (SNPs) might correlate with postburn outcomes. COMT modulates catecholamine metabolism, and polymorphisms within the rs4680 allele result in variable enzyme activity. Catechol-amines are known to modulate the inflammatory process and may affect scar formation. The aim of this study was to determine whether variants in the rs4680 SNP of the COMT gene are associated with post-burn pruritus and scarring. METHODS: Adult burn patients, admitted between 2007 and 2017, with deep partial-thickness burns or delayed healing provided blood samples for genotyp-ing and self-reported itch scores within 1 year of injury. Scarring was measured using the Vancouver Scar Scale (VSS). Itch scores ≥ 4 and VSS scores >7 were considered severe. Genomic deoxyribonucleic acid was genotyped for the rs4680 SNP using realtime polymerase chain reaction (PCR). RESULTS: Median itch and VSS scores were highest for GG homozygotes and lowest for AA homozygotes. This difference was statistically significant for VSS score (P < 0.0001) and approached significance for itch (P = 0.052). After accounting for confounding variables, including race/ethnicity, age, sex, and burn size, the GG homozygotes demonstrated worse scarring (odds ratio 1.88, P = 0.005) compared to AG heterozygotes whereas the AA homozygotes trended towards a protective effect against scarring (odds ratio 0.71, P = 0.10). itch did not demonstrate a statistically significant difference between rs4680 genotype. CONCLUSIONS: Our analysis identifies a trend between COMT genotype with scarring, with rs4680 genetic variation constituting an independent risk factor for VSS score.

National Institute on Disability, Independent Living, and Rehabilitation Research Burn Model System: Review of Program and Database.

The Burn Model System (BMS) centers program was created in 1994 to evaluate the long-term outcomes of burn injuries. As part of this multicenter program, a comprehensive longitudinal database was developed to facilitate the study of a number of functional and psychosocial outcomes after burn injury. In this article, we provide an overview of the data collection procedures, measures selection process, and an overview of the participant data collected between 1994 and 2016. Surveys were administered during hospitalization and at 6, 12, and 24 months after discharge, and in the most recent funding cycle, data collection at every 5 years postinjury was added. More than 7200 people with burn injury were eligible to participate in the BMS National Longitudinal Database. Of these, >5900 (82%) were alive at discharge and consented to follow-up data collection. The BMS National Longitudinal Database represents a large sample of people with burn injury, including information on demographic characteristics, injury characteristics, and health outcomes. The database is publicly available and can be used to examine the effect of burn injury on long-term outcomes.

Factors Affecting Employment After Burn Injury in the United States: A Burn Model System National Database Investigation.

OBJECTIVE: To investigate the effect of patient and injury characteristics on employment for working-age, adult survivors of burn injury using the multicenter Burn Model System national database. DESIGN: Longitudinal survey. SETTING: Multicenter regional burn centers. PARTICIPANTS: Adult burn survivors (N=967) age≥18 years with known employment status prior to injury were included in the analysis at 12 months after injury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Employment status at 12 months after injury. RESULTS: The analyses determined that those employed preinjury had higher odds of being employed (odds ratio [OR]=8.1; 95% confidence interval [CI], 4.9-13.1). White, non-Hispanic individuals were also more likely to be employed (OR=1.49; 95% CI, 1.0-2.1). Older individuals, females, those with longer hospitalizations, amputation during the acute hospitalization, and those with high pain interference at hospital discharge had lower odds of working after injury. Preinjury living situation, preinjury alcohol and drug misuse, number of acute operations and burn size (total body surface area, %) were not significant predictors of employment status at 12 months after burn injury. CONCLUSION: Preinjury employment remains the most significant predictor for postburn employment. Although past reports have focused on predictors for postburn employment, we believe that we need to seek greater understanding of modifiable risk factors for unemployment and examine issues related to work retention, performance, accommodations, and career trajectories for the working-age survivor of burn injury.

Trends of Burn Injury in the United States: 1990 to 2016.

OBJECTIVE: The aim of this study is to report patterns of burn injury within the United States from 1990 to 2016 with regard to age, sex, geography, and year. SUMMARY BACKGROUND DATA: Advances in the management of burn injuries as well as successful public health efforts have contributed to reductions in the annual incidence and mortality of burns. However, several studies suggest that these reductions are not equally distributed throughout the US population. MAIN OUTCOMES AND MEASURES: The Global Burden of Disease Study 2016 was utilized to collect incidence, mortality, disability-adjusted life years (DALYs), and years lived with disability (YLD) from 1990 to 2016. All measures were computed with 95% uncertainty intervals (UI). RESULTS: The overall incidence of burn injury in the United States has decreased from 215 (95% UI, 183-246) to 140 (95% UI, 117-161) per 100,000. However, the relative mortality of burn injury has been fixed over the 26-year study period. Alaska had the highest rates of burn incidence in 1990 and 2016, closely followed by southeastern states. When adjusted for incidence, relative mortality in 1990 was highest in Alabama and Mississippi and the mortality-incidence ratio increased for these states in 2016. In addition, 35 states also demonstrated an increase in the relative mortality of burn injury during the study period. CONCLUSIONS: Regional trends of burn incidence and mortality are highly variable and are likely due to a multitude of factors. Addressing these disparities will require close examination of the contributing factors of burn injury and severity.

Postacute Care Setting Is Associated With Employment After Burn Injury.

OBJECTIVE: To examine differences in long-term employment outcomes in the postacute care setting. DESIGN: Retrospective review of the prospectively collected Burn Model System National Database. SETTING AND PARTICIPANTS: A total of 695 adult survivors of burn injury enrolled between May 1994 and June 2016 who required postacute care at a Burn Model System center following acute care discharge were included. Participants were divided into 2 groups based on acute care discharge disposition. Those who received postacute care at an inpatient rehabilitation facility (IRF) following acute care were included in the IRF group (N=447), and those who were treated at a skilled nursing facility, long-term care hospital, or other extended-care facility following acute care were included in the Other Rehab group (N=248). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Employment status at 12 months postinjury. Propensity score matching and logistic regression were utilized to determine the effect of postacute care setting on employment status. RESULTS: Individuals in the IRF group had larger burns and were more likely to have an inhalation injury and to undergo amputation. At 12 months postinjury, the IRF group had over 9 times increased odds of being employed compared to the Other Rehab group, using propensity score matching (P=.046). CONCLUSIONS: While admitting patients with more severe injuries, IRFs provided a long-term benefit for survivors of burn injury in terms of regaining employment. Given the current lack of evidence-based guidelines on postacute care decisions, the results of this study shed light on the potential benefits of the intensive services provided at IRFs in this population.

MC1R gene polymorphisms are associated with dysfunctional immune responses and wound infection after burn injury.

BACKGROUND: Systemic inflammatory response syndrome (SIRS) is associated with organ failure and infectious complications after major burn injury. Recent evidence has linked melanocortin signaling to anti-inflammatory and wound-repair functions, with mutations in the melanocortin 1 receptor (MC1R) gene leading to increased inflammatory responses. Our group has previously demonstrated that MC1R gene polymorphisms are associated with postburn hypertrophic scarring. Thus, we hypothesized that MC1R single nucleotide polymorphisms (SNPs) would be associated with increased burn-induced SIRS and increased infectious complications. METHODS: We performed a retrospective cohort study of adults (>18 y of age) admitted to our burn center with >20% total body surface area (TBSA) partial/full thickness burns between 2006 and 2013. We screened for five MC1R SNPs (V60L, V92M, R151C, R163Q, T314T) by polymerase chain reaction from genomic DNA isolated from blood samples. We performed a detailed review of each patient chart to identify age, sex, race, ethnicity, %TBSA burned, burn wound infections (BWIs), and 72-hr intravenous fluid volume, the latter a surrogate for a dysfunctional inflammatory response to injury. Association testing was based on multivariable regression. RESULTS: Of 106 subjects enrolled, 82 had complete data for analysis. Of these, 64 (78%) were male, with a median age of 39 and median burn size of 30% TBSA. A total of 36 (44%) subjects developed BWIs. The median total administered IV crystalloid in first 72h was 24.6 L. In multivariate analysis, the R151C variant allele was a significant independent risk factor for BWI (adjusted prevalence ratio 2.03; 95% CI: 1.21-3.39; P = 0.007), and the V60L variant allele was independently associated with increased resuscitation fluid volume (P = 0.021). CONCLUSIONS: This is the first study to demonstrate a significant association between genetic polymorphisms and a nonfatal burn-induced SIRS complication. Our findings suggest that MC1R polymorphisms contribute to dysfunctional responses to burn injury that may predict infectious and inflammatory complications.

Reasons for Distress Among Burn Survivors at 6, 12, and 24 Months Postdischarge: A Burn Injury Model System Investigation.

OBJECTIVE: To identify important sources of distress among burn survivors at discharge and 6, 12, and 24 months postinjury, and to examine if the distress related to these sources changed over time. DESIGN: Exploratory. SETTING: Outpatient burn clinics in 4 sites across the country. PARTICIPANTS: Participants who met preestablished criteria for having a major burn injury (N=1009) were enrolled in this multisite study. INTERVENTIONS: Participants were given a previously developed list of 12 sources of distress among burn survivors and asked to rate on a 10-point Likert-type scale (0=no distress to 10=high distress) how much distress each of the 12 issues was causing them at the time of each follow-up. MAIN OUTCOMES MEASURES: The Medical Outcomes Study 12-Item Short-Form Health Survey was administered at each time point as a measure of health-related quality of life. The Satisfaction With Appearance Scale was used to understand the relation between sources of distress and body image. Finally, whether a person returned to work was used to determine the effect of sources of distress on returning to employment. RESULTS: It was encouraging that no symptoms were worsening at 2 years. However, financial concerns and long recovery time are 2 of the highest means at all time points. Pain and sleep disturbance had the biggest effect on ability to return to work. CONCLUSIONS: These findings can be used to inform burn-specific interventions and to give survivors an understanding of the temporal trajectory for various causes of distress. In particular, it appears that interventions targeted at sleep disturbance and high pain levels can potentially effect distress over financial concerns by allowing a person to return to work more quickly.

Predicting Heterotopic Ossification Early After Burn Injuries: A Risk Scoring System.

OBJECTIVE: The purpose of this study is to develop a scoring system that stratifies burn patients at the time of hospital admission according to risk of developing heterotopic ossification (HO). SUMMARY OF BACKGROUND DATA: HO in burns is an uncommon but severely debilitating problem with a poorly understood mechanism and no fully effective prophylactic measures. METHODS: Data were obtained from the Burn Model System National Database from 1994 to 2010 (n = 3693). The primary outcome is diagnosis of HO at hospital discharge. Logistic regression analysis was used to determine significant demographic and medical predictors of HO. A risk scoring system was created in which point values were assigned to predictive factors and final risk score is correlated with the percent risk of developing HO. The model was internally and externally validated. RESULTS: The mean age of the subjects is 42.5 ±â€Š16.0 years, the mean total body surface area (TBSA) burned is 18.5 ±â€Š16.4%, and the population is 74.9% male. TBSA and the need for grafting of the arm, head/neck, and trunk were significant predictors of HO development (P < 0.01). A 13-point risk scoring system was developed using these significant predictors. The model c-statistic is 0.92. The risk scoring system demonstrated evidence of internal and external validity. An online calculator was developed to facilitate translation of knowledge to practice and research. CONCLUSIONS: This HO risk scoring system identifies high-risk burn patients suitable for diagnostic testing and interventional HO prophylaxis trials.

Hold the Pendulum: Rates of Acute Kidney Injury are Increased in Patients Who Receive Resuscitation Volumes Less than Predicted by the Parkland Equation.

OBJECTIVE: To determine whether restrictive fluid resuscitation results in increased rates of acute kidney injury (AKI) or infectious complications. BACKGROUND: Studies demonstrate that patients often receive volumes in excess of those predicted by the Parkland equation, with potentially detrimental sequelae. However, the consequences of under-resuscitation are not well-studied. METHODS: Data were collected from a multicenter prospective cohort study. Adults with greater than 20% total burned surface area injury were divided into 3 groups on the basis of the pattern of resuscitation in the first 24 hours: volumes less than (restrictive), equal to, or greater than (excessive) standard resuscitation (4 to 6 cc/kg/% total burned surface area). Multivariable regression analysis was employed to determine the effect of fluid group on AKI, burn wound infections (BWIs), and pneumonia. RESULTS: Among 330 patients, 33% received restrictive volumes, 39% received standard resuscitation volumes, and 28% received excessive volumes. The standard and excessive groups had higher mean baseline APACHE scores (24.2 vs 16, P < 0.05 and 22.3 vs 16, P < 0.05) than the restrictive group, but were similar in other characteristics. After adjustment for confounders, restrictive resuscitation was associated with greater probability of AKI [odds ratio (OR) 3.25, 95% confidence interval (95% CI) 1.18-8.94]. No difference in the probability of BWI or pneumonia among groups was found (BWI: restrictive vs standard OR 0.74, 95% CI 0.39-1.40, excessive vs standard OR 1.40, 95% CI 0.75-2.60, pneumonia: restrictive vs standard, OR 0.52, 95% CI 0.26-1.05; excessive vs standard, OR 1.12, 95% CI 0.58-2.14). CONCLUSIONS: Restrictive resuscitation is associated with increased AKI, without changes in infectious complications.

Genomic responses in mouse models poorly mimic human inflammatory diseases.

A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R(2) between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases.

Genome-wide Association Study of Postburn Scarring Identifies a Novel Protective Variant.

OBJECTIVE: To identify genetic variants associated with the severity of postburn hypertrophic scarring (HTS) using a genome-wide approach. BACKGROUND: Risk of severe postburn HTS is known to depend on race, but the genetic determinants of HTS are unknown. METHODS: We conducted a genome-wide association study (GWAS) in a prospective cohort of adults admitted with deep-partial-thickness burns from 2007 through 2014. Scar severity was assessed over time using the Vancouver Scar Scale (VSS), and DNA was genotyped with a >500,000-marker array. We performed association testing of single-nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) >0.01 using linear regression of VSS height score on genotype adjusted for patient and injury characteristics as well as population genetic structure. Array-wide significance was based on Bonferroni correction for multiple testing. RESULTS: Of 538 patients (median age 40 years, median burn size 6.0% of body surface area), 71% were men and 76% were White. The mean VSS height score was 1.2 (range: 0-3). Of 289,639 SNPs tested, a variant in the CUB and Sushi multiple domains 1 (CSMD1) gene (rs11136645; MAF = 0.49), was significantly associated with decreased scar height (regression coefficient = -0.23, P = 7.9 × 10). CONCLUSIONS: In the first published GWAS of HTS, we report that a common intronic variant in the CSMD1 gene is associated with reduced severity of postburn HTS. If this association is confirmed in an independent cohort, investigating the potential role of CSMD1 in wound healing may elucidate HTS pathophysiology.

Morbidity and survival probability in burn patients in modern burn care.

OBJECTIVE: Characterizing burn sizes that are associated with an increased risk of mortality and morbidity is critical because it would allow identifying patients who might derive the greatest benefit from individualized, experimental, or innovative therapies. Although scores have been established to predict mortality, few data addressing other outcomes exist. The objective of this study was to determine burn sizes that are associated with increased mortality and morbidity after burn. DESIGN AND PATIENTS: Burn patients were prospectively enrolled as part of the multicenter prospective cohort study, Inflammation and the Host Response to Injury Glue Grant, with the following inclusion criteria: 0-99 years old, admission within 96 hours after injury, and more than 20% total body surface area burns requiring at least one surgical intervention. SETTING: Six major burn centers in North America. MEASUREMENTS AND MAIN RESULTS: Burn size cutoff values were determined for mortality, burn wound infection (at least two infections), sepsis (as defined by American Burn Association sepsis criteria), pneumonia, acute respiratory distress syndrome, and multiple organ failure (Denver 2 score>3) for both children (<16 yr) and adults (16-65 yr). Five hundred seventy-three patients were enrolled, of which 226 patients were children. Twenty-three patients were older than 65 years and were excluded from the cutoff analysis. In children, the cutoff burn size for mortality, sepsis, infection, and multiple organ failure was approximately 60% total body surface area burned. In adults, the cutoff for these outcomes was lower, at approximately 40% total body surface area burned. CONCLUSIONS: In the modern burn care setting, adults with over 40% total body surface area burned and children with over 60% total body surface area burned are at high risk for morbidity and mortality, even in highly specialized centers.

Benchmarking outcomes in the critically injured burn patient.

OBJECTIVE: To determine and compare outcomes with accepted benchmarks in burn care at 6 academic burn centers. BACKGROUND: Since the 1960s, US morbidity and mortality rates have declined tremendously for burn patients, likely related to improvements in surgical and critical care treatment. We describe the baseline patient characteristics and well-defined outcomes for major burn injuries. METHODS: We followed 300 adults and 241 children from 2003 to 2009 through hospitalization, using standard operating procedures developed at study onset. We created an extensive database on patient and injury characteristics, anatomic and physiological derangement, clinical treatment, and outcomes. These data were compared with existing benchmarks in burn care. RESULTS: Study patients were critically injured, as demonstrated by mean % total body surface area (TBSA) (41.2 ± 18.3 for adults and 57.8 ± 18.2 for children) and presence of inhalation injury in 38% of the adults and 54.8% of the children. Mortality in adults was 14.1% for those younger than 55 years and 38.5% for those aged 55 years and older. Mortality in patients younger than 17 years was 7.9%. Overall, the multiple organ failure rate was 27%. When controlling for age and % TBSA, presence of inhalation injury continues to be significant. CONCLUSIONS: This study provides the current benchmark for major burn patients. Mortality rates, notwithstanding significant % TBSA and presence of inhalation injury, have significantly declined compared with previous benchmarks. Modern day surgical and medically intensive management has markedly improved to the point where we can expect patients younger than 55 years with severe burn injuries and inhalation injury to survive these devastating conditions.

An Executive Summary of the National Trauma Research Action Plan (NTRAP).

ABSTRACT: The National Trauma Research Action Plan (NTRAP) project successfully engaged multidisciplinary experts to define opportunities to advance trauma research and has fulfilled the recommendations related to trauma research from the National Academies of Sciences, Engineering and Medicine (NASEM) report. These panels identified more than 4,800 gaps in our knowledge regarding injury prevention and the optimal care of injured patients and laid out a priority framework and tools to support researchers to advance this field. Trauma research funding agencies and researchers can use this executive summary and supporting manuscripts to strategically address and close the highest priority research gaps. Given that this is the most significant public health threat facing our children, young adults, and military service personnel, we must do better in prioritizing these research projects for funding and providing grant support to advance this work. Through the Coalition for National Trauma Research (CNTR), the trauma community is committed to a coordinated, collaborative approach to address these critical knowledge gaps and ultimately reduce the burden of morbidity and mortality faced by our patients.

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).

Differentiation state determines neural effects on microvascular endothelial cells.

Growing evidence indicates that nerves and capillaries interact paracrinely in uninjured skin and cutaneous wounds. Although mature neurons are the predominant neural cell in the skin, neural progenitor cells have also been detected in uninjured adult skin. The aim of this study was to characterize differential paracrine effects of neural progenitor cells and mature sensory neurons on dermal microvascular endothelial cells. Our results suggest that neural progenitor cells and mature sensory neurons have unique secretory profiles and distinct effects on dermal microvascular endothelial cell proliferation, migration, and nitric oxide production. Neural progenitor cells and dorsal root ganglion neurons secrete different proteins related to angiogenesis. Specific to neural progenitor cells were dipeptidyl peptidase-4, IGFBP-2, pentraxin-3, serpin f1, TIMP-1, TIMP-4 and VEGF. In contrast, endostatin, FGF-1, MCP-1 and thrombospondin-2 were specific to dorsal root ganglion neurons. Microvascular endothelial cell proliferation was inhibited by dorsal root ganglion neurons but unaffected by neural progenitor cells. In contrast, microvascular endothelial cell migration in a scratch wound assay was inhibited by neural progenitor cells and unaffected by dorsal root ganglion neurons. In addition, nitric oxide production by microvascular endothelial cells was increased by dorsal root ganglion neurons but unaffected by neural progenitor cells.