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Sood R.F.,Medicine Regional Burn Center | Gibran N.S.,Medicine Regional Burn Center | Arnoldo B.D.,University of Texas at Dallas | Gamelli R.L.,University of Texas Medical Branch | And 2 more authors.
Journal of Trauma and Acute Care Surgery | Year: 2016

Background In the patient with burn injury, older age, larger percentage of total body surface area (TBS) burned, and inhalation injury are established risk factors for death, which typically Results from multisystem organ failure and sepsis, implicating burn-induced immune dysregulation as a contributory mechanism. We sought to identify early transcriptomic changes in circulating leukocytes underlying increased mortality associated with these three risk factors. Methods We performed a retrospective analysis of the Glue Grant database. From 2003 to 2010, 324 adults with 20% or greater TBS burned were prospectively enrolled at five US burn centers, and 112 provided blood samples within 1 week after burn. RNA was extracted from pooled leukocytes for hybridization onto Affymetrix HU133 Plus 2.0 GeneChips. A multivariate regression model was constructed to determine risk factors for mortality. Testing for differential gene association associated with age, burn size, and inhalation injury was based on linear models using a fold change threshold of 1.5 and false discovery rate of 0.05. Results After adjusting for potential confounders, age greater than 60 years (relative risk [RR], 4.53; 95% confidence interval [CI], 2.93-6.99), burn size greater than 40% TBS (RR, 4.24; 95% CI, 2.61-6.91), and inhalation injury (RR, 2.08; 95% CI, 1.35-3.21) were independently associated with mortality. No genes were differentially expressed in association with age greater than 60 years or inhalation injury. Fifty-one probe sets representing 39 unique genes were differentially expressed in leukocytes from patients with burn size greater than 40% TBS; these genes were associated with platelet activation and degranulation/exocytosis, and gene-set enrichment analysis suggested increased cellular proliferation and down-regulation of proinflammatory cytokines. Conclusion Among adults with large burns, older age, increasing burn size, and inhalation injury have a modest effect on the leukocyte transcriptome in the context of the "genomic storm" induced by a 20% or greater than TBS burned. The 39-gene signature we identified may provide novel targets for the development of therapies to reduce morbidity and mortality associated with burns greater than 40% TBS. Level of Evidence Epidemiologic study, level III. © 2016 Wolters Kluwer Health, Inc. All rights reserved. Source

Stewart B.T.,University of Washington | Stewart B.T.,Kwame Nkrumah University Of Science And Technology | Gyedu A.,Kwame Nkrumah University Of Science And Technology | Agbenorku P.,Kwame Nkrumah University Of Science And Technology | And 5 more authors.
International Journal of Surgery | Year: 2015

Background: Burns are common in low- and middle-income countries (LMICs) and complicated by unhygienic conditions, malnutrition, use of high-risk homemade dressings and delayed presentation. Resultantly, use of routine systemic antibiotic prophylaxis (SAP) to prevent wound infection is common practice despite this intervention being abandoned in high-income countries due to increased antimicrobial resistance and non-bacterial suprainfection. Methods: A best evidence topic (BET) was constructed using a structured protocol. The question addressed was: In LMICs, does routine use of SAP reduce burn wound infection, morbidity or mortality? Results: From 704 retrieved records, 48 reports met criteria to be examined. Of those, 3 studies represented the best available evidence. Together, two randomized clinical trials (RCTs) and a retrospective cohort study reported no difference in the proportion of wound infection, any infection or length of hospital stay between SAP groups and controls. One RCT described a greater proportion of wounds infected with P. aeruginosa among SAP arms compared to controls. The studies had few participants and significant methodological weaknesses. Conclusion: On the basis of limited, currently available evidence, the use of SAP cannot be recommended for patients in LMICs that present soon after burn injury. © 2015 IJS Publishing Group Limited. Source

Sood R.F.,Medicine Regional Burn Center | Hocking A.M.,Medicine Regional Burn Center | Muffley L.A.,Medicine Regional Burn Center | Ga M.,Medicine Regional Burn Center | And 5 more authors.
Journal of Investigative Dermatology | Year: 2015

The genetic determinants of post-burn hypertrophic scarring (HTS) are unknown, and melanocortin 1 receptor (MC1R) loss-of-function leads to fibrogenesis in experimental models. To examine the associations between self-identified race and MC1R single-nucleotide polymorphisms (SNPs) with severity of post-burn HTS, we conducted a prospective cohort study of burned adults admitted to our institution over 7 years. Subjects were evaluated using the Vancouver Scar Scale (VSS), asked to rate their itching, and genotyped for 8 MC1R SNPs. Testing for association with severe HTS (VSS>7) and itch severity (0-10) was based on multivariate regression with adjustment for known risk factors. Of 425 subjects analyzed, 77% identified as White. The prevalence of severe HTS (VSS>7) was 49%, and the mean itch score was 3.9. In multivariate analysis, Asian (prevalence ratio (PR) 1.54; 95% CI: 1.13-2.10), Black/African American (PR 1.86; 95% CI: 1.42-2.45), and Native American (PR 1.87; 95% CI: 1.48-2.35) race were independently associated with severe HTS. MC1R SNP R163Q was also significantly (P<0.001) associated with severe HTS. Asian race (linear regression coefficient 1.32; 95% CI: 0.23-2.40) but not MC1R SNP genotype was associated with increased itch score. We conclude that MC1R genotype may influence post-burn scarring. Source

Sood R.F.,Medicine Regional Burn Center | Arbabi S.,Medicine Regional Burn Center | Honari S.,Medicine Regional Burn Center | Gibran N.S.,Medicine Regional Burn Center
PLoS ONE | Year: 2016

Background: Hypertrophic scarring (HTS) is hypothesized to have a genetic mechanism, yet its genetic determinants are largely unknown. The mitogen-activated protein kinase (MAPK) pathways are important mediators of inflammatory signaling, and experimental evidence implicates MAPKs in HTS formation. We hypothesized that single-nucleotide polymorphisms (SNPs) in MAPK-pathway genes would be associated with severity of post-burn HTS. Methods: We analyzed data from a prospective-cohort genome-wide association study of post-burn HTS. We included subjects with deep-partial-thickness burns admitted to our center who provided blood for genotyping and had at least one Vancouver Scar Scale (VSS) assessment. After adjusting for HTS risk factors and population stratification, we tested MAPK-pathway gene SNPs for association with the four VSS variables in a joint regression model. In addition to individual-SNP analysis, we performed gene-based association testing. Results: Our study population consisted of 538 adults (median age 40 years) who were predominantly White (76%) males (71%) admitted to our center from 2007-2014 with small-to-moderate-sized burns (median burn size 6% total body surface area). Of 2,146 SNPs tested, a rare missense variant in the PTPN5 gene (rs56234898; minor allele frequency 1.5%) was significantly associated with decreased severity of post-burn HTS (P = 1.3×10-6). In genebased analysis, PTPN5 (P = 1.2×10-5) showed a significant association and BDNF (P = 9.5×10-4) a borderline-significant association with HTS severity. Conclusions: We report PTPN5 as a novel genetic locus associated with HTS severity. PTPN5 is a MAPK inhibitor expressed in neurons, suggesting a potential role for neurotrophic factors and neuroinflammatory signaling in HTS pathophysiology. © 2016 Sood et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Source

Thompson C.M.,Medicine Regional Burn Center | Sood R.F.,Medicine Regional Burn Center | Honari S.,Medicine Regional Burn Center | Carrougher G.J.,Medicine Regional Burn Center | Gibran N.S.,Medicine Regional Burn Center
Burns | Year: 2015

Introduction Reliable characterization of a hypertrophic scar (HTS) is integral to epidemiologic studies designed to identify clinical and genetic risk factors for HTS. The Vancouver Scar Scale (VSS) has been widely used for this purpose; however, no publication has defined what score on this scale corresponds to a clinical diagnosis of HTS. Methods In a survey of 1000 burn care providers, we asked respondents what VSS score indicates a HTS and asked them to score scar photos using the VSS. We used receiver-operating-characteristic (ROC) curves to evaluate VSS sub-scores and their combinations in diagnosis of HTS. Results Of 130 responses (13.5%), most were physicians (43.9%) who had worked in burn care for over 10 years (63.1%) and did not use the VSS in clinical practice (58.5%). There was no consensus as to what VSS score indicates a diagnosis of HTS. VSS height score (0-3) performed best for diagnosis of HTS; using a cut-off of ≥ 1, height score was 99.5% sensitive and 85.9% specific for HTS. Conclusions Burn clinicians do not routinely use the VSS and perceptions vary widely regarding what constitutes a HTS. When a dichotomous variable is needed, the VSS height score with a cut-off of ≥ 1 may be optimal. Our findings underscore the need for an objective tool to reproducibly characterize HTS across burn centers. © 2015 Elsevier Ltd and ISBI. All rights reserved. Source

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