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1.
Ann Surg ; 275(5): 1002-1005, 2022 05 01.
Article in English | MEDLINE | ID: mdl-32976278

ABSTRACT

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.


Subject(s)
Burns , Catechol O-Methyltransferase , Cicatrix, Hypertrophic , Pruritus , Adult , Burns/complications , Burns/pathology , Catechol O-Methyltransferase/genetics , Cicatrix, Hypertrophic/etiology , Cicatrix, Hypertrophic/genetics , Genotype , Humans , Polymorphism, Single Nucleotide , Prospective Studies , Pruritus/etiology , Pruritus/genetics
2.
J Burn Care Res ; 42(6): 1227-1231, 2021 11 24.
Article in English | MEDLINE | ID: mdl-34105730

ABSTRACT

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute, life-threatening diseases that cause sloughing of the skin and mucous membranes. Despite improved survival rates, few studies focus on long-term outcomes. We conducted a single-center review of all patients with SJS/TEN admitted from January 2008 to 2014. SJS/TEN survivors were invited to participate in the validated Veterans RAND 12-Item Health Survey (VR-12) to assess health-related quality of life using a mental health composite score and physical health component score (PCS). The sample was compared to U.S. norms using one-sample two-tailed t tests. A second questionnaire addressed potential long-term medical complications related to SJS/TEN. Of 81 treated subjects, 24 (30%) long-term survivors responded. Participants identified cutaneous sequelae most frequently (79%), followed by nail problems (70%), oral (62%), and ocular (58%) sequalae. Thirty-eight percent rated their quality of life to be "unchanged" to "much better" since their episode of SJS/TEN. The average PCS was lower than U.S. population norms (mean: 36 vs 50, P = .006), indicating persistent physical sequelae from SJS/TEN. These results suggest that SJS/TEN survivors continue to suffer from long-term complications that impair their quality of life and warrant ongoing follow-up by a multidisciplinary care team.


Subject(s)
Burns/psychology , Health Status , Quality of Life/psychology , Severity of Illness Index , Stevens-Johnson Syndrome/psychology , Survivors/psychology , Adult , Attitude to Health , Burns/rehabilitation , Female , Humans , Male , Middle Aged , Physical Examination/methods , Retrospective Studies , Stevens-Johnson Syndrome/rehabilitation
3.
Telemed J E Health ; 25(1): 25-30, 2019 01.
Article in English | MEDLINE | ID: mdl-29733269

ABSTRACT

INTRODUCTION: Burn care requires multiple disciplines to collaborate to achieve best patient care. Because of this, rounds involve a very large burn team to assess patients' wounds and formulate plans. To decrease the amount of team members on rounds, our burn center implemented a new budding technology: telemedicine. We created "Zoom Rounds," a Health Insurance Portability and Accountability Act (HIPAA)-compliant, secure videoconferencing system to relay patient wound evaluations to a remote conference room where team members can participate digitally. We sought to evaluate this new rounding process by querying the burn team, patients, and families regarding their experience. METHODS: Surveys were developed for each group and were distributed over a 2-month period. Respondents were asked to rate the videoconferencing rounding experience and comment on the educational experience (staff/providers) and one's personal experience (patient/family). We analyzed both the quantitative data with the qualitative responses. Qualitative data analysis for content was used to independently code and analyze responses to the open-ended survey questions by two authors and verified by adjudication review. RESULTS: Thirty-three patients/families and 69 burn staff members completed the confidential survey (response rate of 90% and 83%, respectively). Coded responses identified several themes: inconsistent technology, improved visualization and communication regarding the wounds, better learning experience, and improved patient experience by decreased crowds in the room. CONCLUSIONS: There was strong support for the use of videoconferencing for patient wound rounds among providers, burn center staff, and patients/families. Telemedicine is a promising technology to improve inpatient burn rounds.


Subject(s)
Burn Units/organization & administration , Burns/therapy , Patient Care Team/organization & administration , Teaching Rounds/organization & administration , Telemedicine/organization & administration , Adolescent , Adult , Aged , Attitude of Health Personnel , Cooperative Behavior , Family/psychology , Female , Health Knowledge, Attitudes, Practice , Humans , Male , Middle Aged , Patient Satisfaction , Videoconferencing/organization & administration , Young Adult
4.
J Surg Res ; 231: 448-452, 2018 11.
Article in English | MEDLINE | ID: mdl-30278967

ABSTRACT

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.


Subject(s)
Burns/complications , Polymorphism, Single Nucleotide , Receptor, Melanocortin, Type 1/genetics , Systemic Inflammatory Response Syndrome/genetics , Wound Infection/genetics , Adolescent , Adult , Aged , Burns/genetics , Burns/immunology , Female , Genetic Markers , Genotyping Techniques , Humans , Linear Models , Male , Middle Aged , Multivariate Analysis , Receptor, Melanocortin, Type 1/immunology , Retrospective Studies , Systemic Inflammatory Response Syndrome/immunology , Wound Infection/immunology , Young Adult
5.
PLoS One ; 11(2): e0149206, 2016.
Article in English | MEDLINE | ID: mdl-26872063

ABSTRACT

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 gene-based 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.


Subject(s)
Burns/complications , Cicatrix, Hypertrophic/etiology , Cicatrix, Hypertrophic/genetics , Mitogen-Activated Protein Kinases/immunology , Polymorphism, Single Nucleotide , Protein Tyrosine Phosphatases, Non-Receptor/genetics , Adult , Cicatrix, Hypertrophic/immunology , Female , Genome-Wide Association Study , Humans , Male , Middle Aged , Mutation, Missense , Prospective Studies , Protein Tyrosine Phosphatases, Non-Receptor/immunology
6.
J Burn Care Res ; 37(2): 127-34, 2016.
Article in English | MEDLINE | ID: mdl-26132051

ABSTRACT

As health-care complexity and costs increase, evidence-based research has become essential to the advancement of burn care. Multicenter trials involve procedures, regulations, and guidelines that require meticulous attention to details and strict adherence to compliance issues. Taking on a large, multicenter trial can be a daunting task for a new burn research coordinator. The purpose of this article is to provide a resource for new burn research coordinators in multicenter clinical trial planning, especially in the field of burns. The burn research coordinator must possess organizational and multitasking skills, attention to detail, professionalism, initiative, and motivation. The burn research coordinator must exercise five principles of practice: compliance, confidentiality, consistency and correctness, and collaboration. Compliance assures subject safety, study integrity, and burn center reputation. Confidentiality is essential, especially when handling sensitive health information. Maintaining subject privacy through secure links and destruction of linked data in a timely matter protects the subjects and complies with the regulations of many governing bodies. Consistency and correctness minimize human errors through continuous data validation and self-auditing and peer auditing. Collaboration between the Principal Investigator/burn research coordinator and all departments involved in the study maintains the study focus and allows for enforcement of procedures. Preparing a budget confirms adequate compensation for work done by the research team and can be broken down into the following five steps: protocol review, calculation of initial payment, establishment of indirect costs, calculation of direct costs, and budget negotiation. Over time, one becomes familiar with the details involved with study success. Advocating for subject safety and protocol adherence are of highest priority. Study design is the most important element that dictates the success of the study. Anticipating the direct and indirect costs of a particular trial assures that the study can be completed with adequate allotment for staff time, laboratory costs, and supplies. Regular communication with the Principal Investigator, clinical staff, and consultants is vital for study completion. An essential contributor to burn research and the advancement of burn care, the burn research coordinator must balance many study-related tasks. Through the practice of compliance, confidentiality, and organization/planning, the burn research coordinator can ensure proper study management. These recommendations may assist new burn research coordinators in their practice.


Subject(s)
Biomedical Research , Burn Units , Professional Role , Research Personnel , Clinical Trials as Topic , Humans , Multicenter Studies as Topic , National Institutes of Health (U.S.) , United States
7.
J Burn Care Res ; 37(3): e218-26, 2016.
Article in English | MEDLINE | ID: mdl-25882517

ABSTRACT

Studies in children with burn injuries have demonstrated that propranolol improves metabolism and reduces muscle protein wasting. However, safety and efficacy in adults are less well established than in children. The purpose of this study was to determine safety of propranolol use in adult patients with burn injuries. Medical records were reviewed for burn-injured adults receiving propranolol. Patients between 18 and 65 years old and with ≥20% TBSA burn were included. Fifty-four patients met the criteria with mean age of 37 years and mean burn size of 38% TBSA. Propranolol dosages ranged from 0.1 to 3.8 mg/kg/day, with an average maximum dosage of 0.61 mg/kg/day. Mean heart rate decreased by 25% during 4 weeks. Seventy-two percent of patients experienced at least one episode of hypotension and 15% experienced bradycardia. Propranolol doses were most frequently held for low blood pressure; 32% of patients had at least one dose held for hypotension. This retrospective analysis suggests that modest dosing of propranolol results in frequent episodes of hypotension or bradycardia. Our data suggest that adults do not tolerate the higher doses reported in a pediatric population. Despite potential beneficial anti-catabolic effects of propranolol, burn care providers must recognize potential iatrogenic hemodynamic effects of this intervention. Our data support the need for prospective multicenter studies to delineate the safety and efficacy of propranolol in adult burn-injured patients.


Subject(s)
Burns/drug therapy , Propranolol/administration & dosage , Adult , Aged , Bradycardia/chemically induced , Female , Humans , Hypotension/chemically induced , Male , Middle Aged , Retrospective Studies , Young Adult
8.
Ann Surg ; 262(4): 563-9, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26366535

ABSTRACT

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.


Subject(s)
Burns/complications , Cicatrix, Hypertrophic/genetics , Genome-Wide Association Study , Membrane Proteins/genetics , Polymorphism, Single Nucleotide , Adolescent , Adult , Aged , Aged, 80 and over , Burns/genetics , Cicatrix, Hypertrophic/etiology , Female , Follow-Up Studies , Gene Frequency , Genetic Markers , Genotyping Techniques , Humans , Linear Models , Male , Middle Aged , Prospective Studies , Severity of Illness Index , Tumor Suppressor Proteins , Young Adult
9.
Burns ; 41(7): 1442-8, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26141527

ABSTRACT

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.


Subject(s)
Burns/complications , Cicatrix, Hypertrophic/classification , Injury Severity Score , Burn Units/statistics & numerical data , Cicatrix, Hypertrophic/etiology , Cicatrix, Hypertrophic/pathology , Humans , Sensitivity and Specificity , Severity of Illness Index , United States
10.
J Invest Dermatol ; 135(10): 2394-2401, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26030184

ABSTRACT

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.


Subject(s)
Burns/blood , Cicatrix, Hypertrophic/ethnology , Cicatrix, Hypertrophic/genetics , Polymorphism, Single Nucleotide , Receptor, Melanocortin, Type 1/genetics , Adult , Burns/complications , Burns/therapy , Cicatrix, Hypertrophic/etiology , Cicatrix, Hypertrophic/pathology , Cohort Studies , Female , Genotype , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Poisson Distribution , Prevalence , Prospective Studies , Risk Assessment , Severity of Illness Index , Wound Healing/genetics , Wound Healing/physiology
11.
Ann Surg ; 259(5): 833-41, 2014 May.
Article in English | MEDLINE | ID: mdl-24722222

ABSTRACT

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.


Subject(s)
Benchmarking , Burns/therapy , Critical Care/methods , Multiple Organ Failure/epidemiology , Adolescent , Adult , Age Distribution , Burns/diagnosis , Burns/mortality , Critical Illness , Female , Follow-Up Studies , Hospital Mortality/trends , Humans , Incidence , Length of Stay/trends , Male , Middle Aged , Multiple Organ Failure/etiology , Prospective Studies , Retrospective Studies , Trauma Severity Indices , United States/epidemiology , Young Adult
12.
J Burn Care Res ; 35(1): 21-7, 2014.
Article in English | MEDLINE | ID: mdl-24043234

ABSTRACT

To date there is limited evidence of efficacy for rapid response teams (RRT) in burns despite widespread their implementation in U.S. hospitals. The burn surgery/acute care ward at the Harborview Medical Center, Seattle, Washington, primarily treats burns, acute wounds, and pediatric trauma patients, but also accepts overflow surgical and medical patients. The authors hypothesize that institutional RRT implementation in 2006 has reduced code blue activations, unplanned intensive care unit (ICU) transfers, and mortality on the acute care ward of this hospital. The authors retrospectively analyzed all patients treated in our acute care unit before (2000-2004) and after RRT implementation (2007-2011). Patient, injury, and treatment outcomes information were collected and analyzed. The authors specifically examined clinical signs that triggered RRT activation and processes of care after activation. They compared code blue activation rates, unplanned ICU transfers, and mortality between the two periods by Poisson regression. The acute care unit treated 7092 patients before and 9357 patients after RRT implementation. There were 409 RRT activations in 329 patients, 18 of whom ultimately died during hospitalization. Those who died had higher rates of stridor (P = .03), tachypnea (P = .001), and low oxygen saturations (P = .02) compared with survivors. Fewer burn and surgical patients died after implementation (seven patients; 22% of all deaths) compared with patients who died pre-RRT (27 patients; 53% of all deaths). After adjustment for case-mix index, age, and medical service differences between the two periods, code blue calls decreased from 1.4/1000 to 0.4/1000 admissions (P = .04), unplanned ICU transfer rates decreased from 65/1000 to 50/1000 admissions (P < .01), and hospital deaths decreased from 4.5/1000 to 3.3/1000 admissions (P = .11). Since its implementation, RRT activation has been frequently used in the acute care ward of this hospital. Respiratory symptoms distinguish RRT patients who die during hospitalization compared with survivors. RRT implementation was associated with fewer code blue activations, unplanned ICU transfers, and a trend toward reduced in-hospital deaths, particularly in burn and surgical patients.


Subject(s)
Hospital Rapid Response Team/organization & administration , Wounds and Injuries/therapy , Adult , Burns/therapy , Cardiopulmonary Resuscitation , Female , Humans , Male , Retrospective Studies , Treatment Outcome , Washington
13.
J Burn Care Res ; 34(5): 507-14, 2013.
Article in English | MEDLINE | ID: mdl-23966116

ABSTRACT

The rising number of obese patients poses new challenges for burn care. These may include adjustments in calculations of burn size, resuscitation, ventilator wean, nutritional goals as well as challenges in mobilization. The authors have focused this observational study on resuscitation in the obese patient population in the first 48 hours after burn injury. Previous trauma studies suggest a prolonged time to reach end points of resuscitation in the obese compared to nonobese injured patients. The authors hypothesize that obese patients have worse outcomes after thermal injury and that differences in the response to resuscitation contribute to this disparity. The authors retrospectively analyzed data prospectively collected in a multicenter trial to compare resuscitation and outcomes in patients stratified by National Institutes of Health/World Health Organization body mass index (BMI) classification (BMI: normal weight, 18.5-24.9; overweight, 25-29.9, obese, 30-39.9; morbidly obese, ≥40). Because of the distribution of body habitus in the obese, total burn size was recalculated for all patients by using the method proposed by Neaman and compared with Lund-Browder estimates. The authors analyzed patients by BMI class for fluids administered and end points of resuscitation at 24 and 48 hours. Multivariate analysis was used to compare morbidity and mortality across BMI groups. The authors identified 296 adult patients with a mean TBSA of 41%. Patient and injury characteristics were similar across BMI categories. No significant differences were observed in burn size calculations by using Neaman vs Lund-Browder formulas. Although resuscitation volumes exceeded the predicted formula in all BMI categories, higher BMI was associated with less fluid administered per actual body weight (P = .001). Base deficit on admission was highest in the morbidly obese group at 24 and 48 hours. Furthermore, the morbidly obese patients did not correct their metabolic acidosis to the extent of their lower BMI counterparts (P values .04 and .03). Complications and morbidities across BMI groups were similar, although examination of organ failure scores indicated more severe organ dysfunction in the morbidly obese group. Compared with being normal weight, being morbidly obese was an independent risk factor for death (odds ratio = 10.1; confidence interval, 1.94-52.5; P = .006). Morbidly obese patients with severe burns tend to receive closer to predicted fluid resuscitation volumes for their actual weight. However, this patient group has persistent metabolic acidosis during the resuscitation phase and is at risk of developing more severe multiple organ failure. These factors may contribute to higher mortality risk in the morbidly obese burn patient.


Subject(s)
Burns/mortality , Cause of Death , Hospital Mortality/trends , Obesity, Morbid/mortality , Resuscitation/mortality , Resuscitation/methods , Adult , Aged , Body Mass Index , Burns/diagnosis , Burns/therapy , Cohort Studies , Female , Fluid Therapy/methods , Humans , Injury Severity Score , Length of Stay , Logistic Models , Male , Middle Aged , Multicenter Studies as Topic , Multiple Organ Failure/diagnosis , Multiple Organ Failure/mortality , Multiple Organ Failure/therapy , Multivariate Analysis , Obesity, Morbid/diagnosis , Obesity, Morbid/therapy , Predictive Value of Tests , Retrospective Studies , Risk Assessment , Sepsis/diagnosis , Sepsis/mortality , Sepsis/therapy , Survival Analysis
14.
J Burn Care Res ; 34(5): 477-82, 2013.
Article in English | MEDLINE | ID: mdl-23966119

ABSTRACT

Hypertrophic scars (HTSs) occur in 30 to 72% patients after thermal injury. Risk factors include skin color, female sex, young age, burn site, and burn severity. Recent correlations between genetic variations and clinical conditions suggest that single-nucleotide polymorphisms (SNPs) may be associated with HTS formation. The authors hypothesized that an SNP in the p27 gene (rs36228499) previously associated with decreased restenosis after coronary stenting would be associated with lower Vancouver Scar Scale (VSS) measurements and decreased itching. Patient and injury characteristics were collected from adults with thermal burns. VSS scores were calculated at 4 to 9 months after injury. Genotyping was performed using real-time polymerase chain reaction. Logistic regression was used to determine risk factors for HTS as measured by a VSS score >7. Three hundred subjects had a median age of 39 years (range, 18-91); 69% were male and median burn size was 7% TBSA (range, 0.25-80). Consistent with literature, the p27 variant SNP had an allele frequency of 40%, but was not associated with reduced HTS formation or lower itch scores in any genetic model. HTS formation was associated with American Indian/Alaskan Native race (odds ratio [OR], 12.2; P = .02), facial burns (OR, 9.4; P = .04), and burn size ≥20% TBSA (OR, 1.99; P = .03). Although the p27 SNP may protect against vascular fibroproliferation, the effect cannot be generalized to cutaneous scars. This study suggests that American Indian/Alaskan Native race, facial burns, and higher %TBSA are independent risk factors for HTS. The American Indian/Alaskan Native association suggests that there are potentially yet-to-be-identified genetic variants.


Subject(s)
Burns/complications , Cicatrix, Hypertrophic/epidemiology , Cicatrix, Hypertrophic/genetics , Cyclin-Dependent Kinase Inhibitor p27/genetics , Genetic Predisposition to Disease , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Burns/diagnosis , Burns/therapy , Chi-Square Distribution , Cicatrix, Hypertrophic/etiology , Cohort Studies , Female , Follow-Up Studies , Genotype , Humans , Indians, North American/genetics , Injury Severity Score , Logistic Models , Male , Middle Aged , Polymorphism, Single Nucleotide , Prospective Studies , Real-Time Polymerase Chain Reaction/methods , Risk Assessment , Sex Distribution , Young Adult
15.
Proc Natl Acad Sci U S A ; 110(9): 3507-12, 2013 Feb 26.
Article in English | MEDLINE | ID: mdl-23401516

ABSTRACT

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.


Subject(s)
Genomics , Inflammation/genetics , Acute Disease , Adolescent , Adult , Animals , Burns/genetics , Burns/pathology , Disease Models, Animal , Endotoxemia/genetics , Endotoxemia/pathology , Female , Gene Expression Regulation , Humans , Inflammation/pathology , Male , Mice , Mice, Inbred C57BL , Signal Transduction/genetics , Time Factors , Wounds and Injuries/genetics , Wounds and Injuries/pathology , Young Adult
16.
J Burn Care Res ; 33(5): 619-23, 2012.
Article in English | MEDLINE | ID: mdl-22964549

ABSTRACT

Risk and incidence of pressure ulcers (PUs) in the burn population remain poorly understood. The purpose of this study was to determine the timing and incidence of PUs at our regional burn center and to identify early risk factors for PU development in burn patients. A retrospective review of 40 charts was performed from among the 1489 patients admitted to our regional burn center between January 2008 and December 2009. Twenty patients acquired PUs during their admission and were identified on the basis of International Classification of Diseases, ninth revision, designation, hospital stay >7 days, and thermal injury (excluding toxic epidermal necrolysis and purpura fulminans). The remaining 20 patients were matched controls based on ±5 years in age and ±8% TBSA. Patient, injury, and outcome characteristics were compared among patient groups using χ for categorical variables and Mann-Whitney for continuous variables. The incidence of PU was 1.3% of all admissions. PU most commonly occurred at the sacrum/coccyx (eight), lower extremity (seven), and occiput (six). A majority of PU presented at stage 2 (33%), stage 3 (26%), and unstageable (30%). Thirteen were splint or device related and reportable. Ninety percent of patients with PUs presented with a Braden score of 16 or less (P = .03), although 60% of controls also had admission Braden scores less than 16. On an average, PUs were acquired within 17 days of admission. Data suggest burn patients are particularly at risk of developing PU based on admission Braden scores. However, low Braden scores do not necessarily correlate with eventual development of PU. Therefore, early and aggressive PU prevention and risk assessment tools must be used to diagnose PUs at an early and reversible stage.


Subject(s)
Burns/complications , Pressure Ulcer/pathology , Risk Assessment , Adult , Burn Units , Burns/pathology , Case-Control Studies , Chi-Square Distribution , Female , Health Status Indicators , Humans , Incidence , Male , Pressure Ulcer/diagnosis , Pressure Ulcer/etiology , Retrospective Studies , Risk Assessment/methods , Risk Factors , Time Factors
17.
PLoS One ; 7(7): e40086, 2012.
Article in English | MEDLINE | ID: mdl-22792216

ABSTRACT

BACKGROUND: Burn demographics, prevention and care have changed considerably since the 1970s. The objectives were to 1) identify new and confirm previously described changes, 2) make comparisons to the American Burn Association National Burn Repository, 3) determine when the administration of fluids in excess of the Baxter formula began and to identify potential causes, and 4) model mortality over time, during a 36-year period (1974-2009) at the Harborview Burn Center in Seattle, WA, USA. METHODS AND FINDINGS: 14,266 consecutive admissions were analyzed in five-year periods and many parameters compared to the National Burn Repository. Fluid resuscitation was compared in five-year periods from 1974 to 2009. Mortality was modeled with the rBaux model. Many changes are highlighted at the end of the manuscript including 1) the large increase in numbers of total and short-stay admissions, 2) the decline in numbers of large burn injuries, 3) that unadjusted case fatality declined to the mid-1980s but has changed little during the past two decades, 4) that race/ethnicity and payer status disparity exists, and 5) that the trajectory to death changed with fewer deaths occurring after seven days post-injury. Administration of fluids in excess of the Baxter formula during resuscitation of uncomplicated injuries was evident at least by the early 1990s and has continued to the present; the cause is likely multifactorial but pre-hospital fluids, prophylactic tracheal intubation and opioids may be involved. CONCLUSIONS: 1) The dramatic changes include the rise in short-stay admissions; as a result, the model of burn care practiced since the 1970s is still required but is no longer sufficient. 2) Fluid administration in excess of the Baxter formula with uncomplicated injuries began at least two decades ago. 3) Unadjusted case fatality declined to ∼6% in the mid-1980s and changed little since then. The rBaux mortality model is quite accurate.


Subject(s)
Burns/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Burns/economics , Burns/etiology , Burns/therapy , Child , Child, Preschool , Female , Fluid Therapy , History, 20th Century , History, 21st Century , Hospitalization/economics , Humans , Incidence , Infant , Male , Middle Aged , Resuscitation , Transportation of Patients , Washington/epidemiology , Washington/ethnology , Young Adult
18.
J Burn Care Res ; 28(1): 71-5, 2007.
Article in English | MEDLINE | ID: mdl-17211203

ABSTRACT

Heparin-induced thrombocytopenia (HIT) is an antibody-mediated complication of heparin treatment that can result in a number of devastating thrombotic complications. Given the common use of heparin for deep venous thrombosis prophylaxis in patients with burns, we reviewed the incidence and complications of HIT in our burn center. We performed a retrospective review of all patients treated with heparin at our burn center who underwent testing for HIT from 2001 to 2005. Screening for HIT was performed by platelet factor 4 enzyme-linked immunoassay. Records were reviewed with particular attention to indications for HIT testing, duration of heparin therapy, type of heparin used (fractionated vs unfractionated), indication for heparin use (prophylactic vs therapeutic), treatment of HIT, and complications of HIT. During the 4-year study period, 625 patients received heparin therapy at some point during their hospital course. Of these patients, 43 (6.9%) underwent testing for HIT and 10 of the 43 screened patients (23%) were positive; the incidence among all heparinized burn patients was 1.6%. Thrombotic complications of HIT included arterial thrombosis requiring limb amputation (two patients), deep venous thrombosis (three patients), and pulmonary embolism (two patients). One patient died, presumably secondary to a pulmonary embolism. All patients were anticoagulated after HIT diagnosis, and four patients developed bleeding complications. HIT is a potentially devastating complication of heparin administration. Whereas our overall incidence of HIT was low, HIT+ patients developed significant complications, including arterial and venous thrombosis, pulmonary embolus, limb loss, and death. Treatment for such HIT-related thromboses usually resulted in bleeding complications requiring transfusions. The routine use of heparin for deep venous thrombosis prophylaxis needs to be carefully considered in light of these potential complications.


Subject(s)
Anticoagulants/adverse effects , Burns/drug therapy , Heparin/adverse effects , Pulmonary Embolism/etiology , Thrombocytopenia/chemically induced , Thrombosis/etiology , Amputation, Surgical , Anticoagulants/administration & dosage , Blood Transfusion/statistics & numerical data , Burn Units , Burns/complications , Drug Utilization/statistics & numerical data , Female , Heparin/administration & dosage , Humans , Length of Stay , Male , Mass Screening , Middle Aged , Retrospective Studies , Thrombocytopenia/diagnosis , Thrombosis/prevention & control
19.
J Trauma ; 61(5): 1212-7, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17099531

ABSTRACT

BACKGROUND: Integra, a dermal replacement template consisting of bovine collagen, chondroitin-6-sulfate, and a silastic sheet is a postexcisional treatment for deep partial to full thickness burns where autograft is limited. This study correlates Integra histology and quantitative microbiology cultures with clinical outcomes after autografting. METHODS: Charts of 29 burn patients who underwent Integra treatment and neodermis biopsy at the time of ultra thin autografting were reviewed. We analyzed microbial contamination, inflammatory reaction, and autograft take. RESULTS: The mean burn size and age were 43% total body surface area and 39 years old, respectively. In quantitative neodermis cultures, 90% of samples had bacterial growth; nine samples (31%) had > 10(5) colony forming units per gram. The most common organism was Staphylococcus aureus (31%). Patients with quantitative bacterial counts >10(5) CFU/g received targeted systemic antibiotics. Integra take (83%) and autograft take (92%) were acceptable even in patients with high bacterial counts (78% Integra take; 86% autograft take). More than 50% of biopsies had dermal regeneration similar to normal dermis; foreign body reactions were unusual. Histologic evidence of inflammation, especially polymorphonuclear cells, was increased in biopsies with high bacterial counts. CONCLUSION: Integra and autograft take can be acceptable even with high bacterial counts if wounds are treated with appropriate targeted topical and systemic antibiotics in the presence of microbial contamination. Neodermis biopsies showed fibrous in-growth congruent with existing Integra fibers with minimal foreign body reaction. These data support Integra use as a safe and effective treatment modality in patients with major burns.


Subject(s)
Biocompatible Materials/therapeutic use , Burns/therapy , Chondroitin Sulfates , Collagen , Skin, Artificial/microbiology , Surgical Wound Infection/microbiology , Administration, Topical , Adult , Bacitracin/therapeutic use , Colony Count, Microbial , Drug Combinations , Female , Humans , Male , Neomycin/therapeutic use , Polymyxin B/therapeutic use , Retrospective Studies , Skin Transplantation , Surgical Wound Infection/prevention & control , Treatment Outcome
20.
J Burn Care Res ; 27(5): 676-81, 2006.
Article in English | MEDLINE | ID: mdl-16998400

ABSTRACT

The purpose of this investigation was to examine the amount of anxiety patients believed tolerable and the amount of anxiety experienced during routine burn wound care. Participants included 47 hospitalized adults who provided data for four consecutive assessment periods. Patients (mean TBSA, 16%; range, 2-70%) were primarily Caucasian (87%) and had an average hospital stays of 23 days (range, 11-130). Reports of what level of anxiety they would be able to tolerate and what level of anxiety had been experienced were assessed using 10-point Graphic Rating Scales. The use of anxiolytic was recorded, and patient suggestions for reducing anxiety were obtained. The single most commonly endorsed anxiety treatment goal was 0, although 53% consistently chose a treatment goal other than 0 (range, 1-6). Two repeated-measure analyses of variance indicated that the amount of anxiety patients could tolerate and the amount they reported experiencing did not change over the course of time. Paired t-tests revealed that patients routinely reported more anxiety than they considered tolerable. Analyses of anxiety reports of patients treated with anxiolytics (n = 6) vs patients receiving no anxiolytics (n = 41) revealed inconsistent differences in actual anxiety and treatment goals across time. In general, patient suggestions for lessening anxiety included requests for education, communication, additional medications, and manipulation of the hospital environment. Anxiety for burn-injured, hospitalized adults remains a concern. Our findings are consistent with the literature indicating that adult patients hospitalized for burn wound care report appreciable anxiety, over and above what they consider "tolerable." Continued research is needed and should include investigations into the relationship between pain and anxiety during routine wound care.


Subject(s)
Anxiety/epidemiology , Burns/psychology , Hospitalization , Adolescent , Adult , Aged , Analysis of Variance , Anti-Anxiety Agents/therapeutic use , Anxiety/therapy , Bandages , Burns/epidemiology , Burns/therapy , Communication , Debridement , Female , Humans , Hydrotherapy , Lorazepam/therapeutic use , Male , Middle Aged , Needs Assessment , Patient Education as Topic , Prospective Studies , Psychiatric Status Rating Scales , Washington/epidemiology
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