Medicine Regional Burn Center

Seattle, WA, United States

Medicine Regional Burn Center

Seattle, WA, United States
SEARCH FILTERS
Time filter
Source Type

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.


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 | Gyedu A.,Komfo Anokye Teaching Hospital | And 7 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.


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.


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 3 more authors.
Annals of Surgery | Year: 2015

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=7.9×10-8). 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. Copyright © 2015 Wolters Kluwer Health, Inc.


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.


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.


PubMed | University of Washington and Medicine Regional Burn Center
Type: Journal Article | Journal: The 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.


PubMed | Kwame Nkrumah University Of Science And Technology, Medicine Regional Burn Center and Columbia University
Type: | Journal: International journal of surgery (London, England) | Year: 2015

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.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?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.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.


PubMed | Medicine Regional Burn Center
Type: Journal Article | Journal: PloS one | Year: 2016

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.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.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 = 1.310-6). In gene-based analysis, PTPN5 (P = 1.210-5) showed a significant association and BDNF (P = 9.510-4) a borderline-significant association with HTS severity.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.


News Article | October 7, 2016
Site: www.techtimes.com

E-cigarettes, personal vaporizers or electronic nicotine delivery systems (ENDS) seem to undergo an increasing trend among customers. These include people who are smokers, former smokers or individuals who never consumed cigarettes. Their basic design makes them easy to use and because of this many of the users fail to take into consideration the risk of a "thermal runaway," a situation when the internal battery becomes overheated, thus increasing the chances to produce an explosion. Generally, lithium-ion batteries are safe. However, their overheating was responsible for no less than 15 patients who experienced burns in the interval October 2015 - June 2016, as confirmed by the University of Washington Medicine Regional Burn Center. Among the patients, 80 percent had flame burns and a third experienced chemical burns due to the exploding batteries. The Food and Drug Administration (FDA) has only recently started regulating e-cigarettes by extending its authority to cover tobacco products including ENDS. While the battery status of these devices remains unclear, the increasing number of cases raise concerns from the medical team that recently published a study in The New England Journal of Medicine. Until this issue is resolved, both ENDS consumers and their health providers have to be aware of the risks and not minimize the possibility of explosion that is associated with the consumption of e-cigarettes. Among the registered cases, many patients also had their hands affected by the explosion while trying to remove the e-cigarette that exploded from their pockets. "There also have been a lot of injuries to the hands and face when people have had explosions as they've been using them. Patients tell us they had no idea this could happen. They've had little to no warning that the device is going to explode," explained Elisha Brownson, a burn/critical care surgical fellow at the hospital. The team of scientists believe that this issue constitutes a public safety problem, demanding an increase in regulation and drastic monitoring from the FDA. However, there are no manufacturing standards imposed for these devices. The American Vaping Association publicly explained that the risk of e-cigarettes is the same as for any other lithium-ion batteries, from mobile phones to laptops, when used properly. But according to Brownson, some of the batteries could be substandard or mechanically faulty, as there are no authorities responsible for their proper functioning. "Had the authors wanted to give a complete picture rather than just stoke fears, they would have recapped other battery-related injuries to demonstrate that this isn't a problem that is unique to vapor products," declared Gregory Conley, president of the association. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.

Loading Medicine Regional Burn Center collaborators
Loading Medicine Regional Burn Center collaborators