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Nicole S Gibran

Publications and source records attributed to Nicole S Gibran.

At least 19 recordsLinked to original sources

Early leukocyte gene expression associated with age, burn size, and inhalation injury in severely burned adults.

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.

Adult↗

Thermal and electrical injuries.

Through progress in wound management, resuscitation, intensive care treatment, and a coordinated rehabilitation process, modern burn care has been able to deliver substantial increases in survival and improvement in functional outcomes for burn victims. The development of regionalized burn centers has contributed greatly to this progress. As the field of burns matures, burn centers are preparing to meet future challenges through collaborative efforts in disaster management and outcomes research.

Anemia↗

An outcome analysis of patients transferred to a regional burn center: transfer status does not impact survival.

BACKGROUND: Optimal burn care is provided at specialized burn centers. Given the geographic location of these centers, many burn patients receive initial treatment at local emergency departments prior to transfer. The purpose of this study was to determine whether patients transferred from other facilities have worse outcomes than those admitted directly from the field. STUDY DESIGN: A retrospective cohort study was performed comparing the outcomes of patients admitted to our burn center directly from the field with patients requiring transfer from a preliminary care facility. The outcomes of interest were mortality, length of stay, length of stay/TBSA burned, number of operations and hospital charges. Poisson regression or Cox proportional hazards model was used to evaluate differences in outcomes after adjusting for potential confounders. RESULTS: From 2000 to 2003 a total of 1877 patients were admitted to our burn center and 953 (51%) were transferred from a preliminary care facility. No difference (p<0.05) was found in length of stay, number of operations, hospital charges and mortality between the two cohorts. CONCLUSIONS: This study demonstrates that patients transferred to a regional burn center from local hospitals have equivalent mortality, length of stay and hospital charges as those admitted directly from the field.

Adolescent↗

Histology of the thick scar on the female, red Duroc pig: final similarities to human hypertrophic scar.

The etiology and treatment of hypertrophic scar remain puzzles even after decades of research. A significant reason is the lack of an accepted animal model of the process. The female, red Duroc pig model was described long ago. Since the skin of the pig is similar to that of humans, we are attempting to validate this model and found it to be encouraging. In this project we quantified myofibroblasts, mast cells and collagen nodules in the thick scar of the Duroc pig and compared these to the values for human hypertrophic scar. We found the results to be quite similar and so further validated the model. In addition, we observed that soon after wounding an inflammatory cell layer forms. The thickness of the inflammatory layer approaches the thickness of the skin removed as if the remaining dermis "knows" how much dermis is gone. In deep wounds this inflammatory layer thickens and this thickness is predictive of the thickness of the ultimate scar.

Adolescent↗

Effect of blood transfusion on outcome after major burn injury: a multicenter study.

OBJECTIVE: To delineate blood transfusion practices and outcomes in patients with major burn injury. CONTEXT: Patients with major burn injury frequently require multiple blood transfusions; however, the effect of blood transfusion after major burn injury has had limited study. DESIGN: Multicenter retrospective cohort analysis. SETTING: Regional burn centers throughout the United States and Canada. PATIENT POPULATION: Patients admitted to a participating burn center from January 1 through December 31, 2002, with acute burn injuries of >or=20% total body surface area. OUTCOMES MEASURED: Outcome measurements included mortality, number of infections, length of stay, units of blood transfused in and out of the operating room, number of operations, and anticoagulant use. RESULTS: A total of 21 burn centers contributed data on 666 patients; 79% of patients survived and received a mean of 14 units of packed red blood cells during their hospitalization. Mortality was related to patient age, total body surface area burn, inhalation injury, number of units of blood transfused outside the operating room, and total number of transfusions. The number of infections per patient increased with each unit of blood transfused (odds ratio, 1.13; p<.001). Patients on anticoagulation during hospitalization received more blood than patients not on anticoagulation (16.3+/-1.5 vs. 12.3+/-1.5, p<.001). CONCLUSIONS: The number of transfusions received was associated with mortality and infectious episodes in patients with major burns even after factoring for indices of burn severity. The utilization of blood products in the treatment of major burn injury should be reserved for patients with a demonstrated physiologic need.

Adult↗

Incidence and characteristics of hospitalized patients with pressure ulcers: State of Washington, 1987 to 2000.

BACKGROUND: Pressure ulcers complicate the hospital course of critically injured or ill patients. Guidelines have been promulgated to prevent pressure ulcers in hospitalized patients. The purpose of this study was to determine whether these guidelines have, in fact, reduced the incidence of pressure sores. METHODS: The authors examined census data from the National Center for Health Statistics and the Washington State Department of Health for the 14-year period 1987 through 2000 and identified patients with a pressure ulcer listed as the primary diagnosis (International Classification of Diseases, Ninth Revision, Clinical Modification code 707.0) and patients admitted for other diagnoses with pressure ulcer as a secondary diagnosis. The authors reasoned that patients who were admitted for treatment of pressure ulcers would have the diagnosis listed as primary, whereas those who were admitted for other reasons and developed pressure ulcers during the admission would have pressure ulcer listed as a secondary diagnosis. Other available data included patient age, sex, procedures for pressure ulcers (International Classification of Diseases, Ninth Revision, Clinical Modification codes 15920 through 15999), length of stay, and hospital charges for care. RESULTS: The incidence of pressure ulcers as a primary diagnosis varied from 7.0 to 8.3 per 100,000 population but did not change over the 14-year study period. The rate of operation for these ulcers also did not change. The incidence of pressure ulcers as either a primary or secondary diagnosis doubled from 34.5 to 71.6 per 100,000 (p < 0.001), whereas the incidence of operative procedures for these ulcers did not change. CONCLUSION: The authors found no evidence that the guidelines for the prevention of pressure ulcers have been effective in decreasing pressure ulcer formation, but it may be that pressure ulcers are now being reported in a more thorough manner.

Adult↗

Complex wound management utilizing an artificial dermal matrix.

The benefits of the Integra Dermal Regeneration Template in the management of extensive burn injuries have been well documented. Integra can reduce donor- and graft-site scarring and has been reported to be capable of vascularizing over small areas of exposed bone and tendon. Given these potential advantages, we have used Integra for a variety of other reconstruction applications. We performed a retrospective review of patients with complex wounds treated with Integra at our burn center. Integra was used in the management of a variety of wounds, including necrotizing fasciitis, extremity degloving injury, meningococcemia, Marjolin ulcer, postburn lip reconstruction, and fourth-degree burns with exposed bone or tendon. Engraftment rates of Integra and autograft were 98% +/- 4% and 97% +/- 4%, respectively. All areas of graft loss healed without need for regrafting. The benefits of Integra in the management of acute burn wounds can be extended to other traumatic and complex wounds.

Adolescent↗

Correlation of clinical outcome of integra application with microbiologic and pathological biopsies.

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.

Administration, Topical↗

Elevated orbital pressure: another untoward effect of massive resuscitation after burn injury.

BACKGROUND: Fluid resuscitation remains a fundamental component of early burn care management. However, recent studies suggest that excessive volumes of resuscitation are being administered. Overresuscitation results in negative sequelae including abdominal and extremity compartment syndromes. Elevated intraocular pressure (IOP) has been described as another potentially devastating effect of massive fluid resuscitation in trauma patients. The orbit, similar to the abdomen and extremity, is a compartment, limited to expansion from edema anteriorly by the eyelids and orbital septum, and posteriorly by the bony orbital walls. The purpose of this study was to review the incidence of elevated IOP in a series of patients with major burn injury. METHODS: We retrospectively reviewed the charts of 13 consecutive patients admitted to our burn center with burn sizes >25% total body surface area (TBSA). All patients underwent serial IOP measurements for the first 72 hours following admission. Medical records were reviewed for fluid resuscitation volume, IOP measurements, need for canthotomy, and results of canthotomy procedures. RESULTS: Five of 13 patients had IOP >30 mm Hg and required lateral canthotomy. Canthotomy immediately reduced IOP (p = 0.009). Patients who developed elevated IOP received a significantly larger fluid resuscitation (9.0 cc/kg/%TBSA versus 6.0 cc/kg/%TBSA, p = 0.02). Elevated IOP was significantly associated with delivery of larger fluid resuscitation volume (p = 0.027). CONCLUSIONS: Massive fluid resuscitation following burn injury can result in orbital compartment syndrome requiring lateral canthotomy. Early diagnosis and treatment of orbital compartment syndrome should be incorporated into the management of patients with major burn injury receiving large fluid resuscitation volume.

Adult↗

The optimal time for early excision in major burn injury.

INTRODUCTION: Early excision and grafting (E&G) drastically changed burn care in America by reducing morbidity, mortality and hospital length of stay (LOS). The present study was intended to determine whether an optimal time window exists between resuscitation and wound sepsis for the first E&G in a patient with a large burn. MATERIAL AND METHOD: The authors conducted a retrospective study of patients admitted between January 1994 and December 2000 with > or = 40% TBSA burns and at least 1 E&G procedure. Patients were grouped according to the day of their first operation. Patients allowed to heal indeterminate burns prior to excision and grafting of deep partial or full thickness burns were grouped as > or = d7 and were excluded from the present study. The authors correlated the time of first excision with infection, mortality and LOS. RESULTS: Seventy-five patients were identified and 12 patients allowed to heal indeterminate burn prior to excision and grafting of deep partial or full thickness burns were excluded. Sixty-three remaining patients included 51 males and 12 females. Mean burn size was 49% of total body surface area (TBSA) (44% deep partial or full thickness) and the mean age was 36 years. There were 61 flame (2 combined with electrical injuries), 1 scald and 1 chemical burn. Twelve died (19%) and 52 patients developed 121 infections. Whereas there was no statistical difference in mortality for patients operated on different days (p > 0.2), 60% of patients operated within the first 48 hours after injury died; this was not significant due to a small patient number CONCLUSIONS: The present data suggest that patients who undergo early excision and grafting within seven days following a major burn > or = 40% TBSA have equivalent infection or mortality rates regardless of when the first operation occurs between post burn day(PBD) 2 and PBD 7 (p > 0.2).

Adult↗

Changes in VEGF and nitric oxide after deep dermal injury in the female, red Duroc pig-further similarities between female, Duroc scar and human hypertrophic scar.

Despite decades of research, our understanding of human hypertrophic scar is limited. A reliable animal model could significantly increase our understanding. We previously confirmed similarities between scarring in the female, red, Duroc pig and human hypertrophic scarring. The purpose of this study was to: (1) measure vascular endothelial growth factor (VEGF) and nitric oxide (NO) levels in wounds on the female Duroc; and (2) to compare the NO levels to those reported for human hypertrophic scar. Shallow and deep wounds were created on four female Durocs. VEGF levels were measured using ELISA and NO levels with the Griess reagent. VEGF and NO levels were increased in deep wounds at 10 days when compared to shallow wounds (p < 0.05). At 15 weeks, VEGF and NO levels had returned to the level of shallow wounds. At 21 weeks, VEGF and NO levels had declined below baseline levels in deep wounds and the NO levels were significantly lower (p < 0.01). We found that VEGF and NO exhibit two distinctly different temporal patterns in shallow and deep wounds on the female Durocs. Furthermore, NO is decreased in female, Duroc scar as it is in human, hypertrophic scar further validating the usefulness of the model.

Animals↗

Management of facial burns with a collagen/glycosaminoglycan skin substitute-prospective experience with 12 consecutive patients with large, deep facial burns.

Management of deep facial burns remains one of the greatest challenges in burn care. We have developed a protocol over the past 20 years for management of facial burns that includes excision and coverage with thick autograft. However, the results were not perfect. Deformities of the eyelids, nose and mouth as well as the prominence of skin graft junctures demonstrated the need to explore novel approaches. Integra has been used with success in the management of burns of the trunk and extremities. The purpose of this study was to prospectively evaluate the aesthetic outcome of the use of Integra for deep facial burns. Twelve consecutive patients underwent excision of large, deep facial burns and placement of Integra. Integra provides excellent color and minimally visible skin graft junctures. The texture is good but not as supple as thick autograft. Integra is not well suited for use in the coverage of eyelid burns due to the need to wait 2 weeks for adequate vascularization. In summary, thick autograft remains the gold standard for deep facial burns. However, for patients with extensive burns and limited donor sites, Integra provides an acceptable alternative.

Adult↗

Patterns of grease burn injury: development of a classification system.

Grease burns occur commonly in the home during food preparation. It has been our observation that grease burns follow a particular pattern of injury. The purpose of this study was to review our institutional experience in the management of these burns to develop a classification scheme. We performed a retrospective review of patients admitted to our burn center with grease burns. Subjects were identified through our database and their charts were reviewed with particular attention to burn distribution, TBSA and need for grafting. We excluded workplace burns and children under the age of six. A total of 249 patients who fit the above criteria were admitted with grease burns to our burn center from 1993 to 2003. The sequence of events leading to burn and its distribution followed a consistent pattern. The majority of patients (86%) had an isolated upper extremity burn or upper extremity burn in combination with a face, trunk or lower extremity burn. Forty percent of patients required at least one excision and grafting procedure. Grease burns associated with cooking at home follow predictable patterns of injury. Based on these patterns we proposed a classification system for domestic grease burns.

Accidental Falls↗

Antioxidants inhibit fatty acid and glucose-mediated induction of neutral endopeptidase gene expression in human microvascular endothelial cells.

BACKGROUND: Neutral endopeptidase (NEP) is a membrane-bound metallopeptidase that degrades tachykinins and may regulate their role in wound repair. NEP enzyme activity is increased in diabetic wounds and skin compared with normal controls. We have shown that unsaturated fatty acids and glucose upregulate NEP activity in human microvascular endothelial cells (HMECs) and that vitamins E and C reduce this effect. STUDY DESIGN: To determine whether these changes involve NEP gene expression regulation, we analyzed NEP mRNA levels in HMECs cultured with elevated glucose (40 mM) and fatty acids oleate (40 microM) and linoleate (40 microM) for 48 hours or 1 month. Cells were exposed for an additional 48 hours to antioxidants vitamins E or C or N-acetylcysteine. Total RNA was extracted and analyzed for NEP mRNA using real-time reverse transcriptase polymerase chain reaction. NEP gene expression was standardized to beta-actin mRNA and results were analyzed using ANOVA. RESULTS: Elevated glucose, oleate, and linoleate upregulated NEP mRNA in short and longterm HMEC cultures, but did not alter rate of NEP mRNA degradation. Vitamins E and C and N-acetylcysteine blocked glucose- and fatty acid-induced NEP mRNA (p < or = 0.05). The potential role of oxidative stress in NEP activation was confirmed by demonstrating that elevated glucose and fatty acids increase H(2)O(2) levels in HMECs. CONCLUSIONS: Regulation of NEP enzyme activity by glucose and fatty acids appears to include gene expression transcription as well as modulation of enzyme activity. Our results also suggest that oxidative stress may be involved in upregulation of NEP by fatty acids and glucose.

Acetylcysteine↗

Substance P levels and neutral endopeptidase activity in acute burn wounds and hypertrophic scar.

BACKGROUND: Substance P, a cutaneous neuroinflammatory mediator released from peripheral nerves, plays a role in responses to injury. Neutral endopeptidase is a cell membrane-bound metallopeptidase enzyme that regulates substance P activity. The question of substance P involvement in hypertrophic scar development has been based on observations that hypertrophic scars have increased numbers of nerves. The authors hypothesized that hypertrophic scar has greater substance P levels and decreased neutral endopeptidase activity compared with uninjured skin and acute partial-thickness burns, which may contribute to an exuberant response to injury. METHODS: The authors obtained small skin samples of deep partial-thickness burns (n = 7; postburn days 7 to 78) and uninjured skin (n = 14) from patients (eight male patients and six female patients; 2 to 71 years old) undergoing burn wound excision. Hypertrophic scar samples were obtained from six patients (three male patients and three female patients; 8 to 47 years old) undergoing surgical excision 13 to 64 months after burn injury. Protein concentrations were determined using a bicinchoninic acid assay. Substance P concentration was determined by means of indirect enzyme-linked immunosorbent assay. Neutral endopeptidase activity was measured using an enzymatic assay that quantifies a fluorescent degradation product, methoxy-2-naphthylamine (MNA). Substance P and neutral endopeptidase data were standardized to sample weight. RESULTS: Substance P levels were greater in hypertrophic scar (3506 pg/g) compared with uninjured skin (1698 pg/g; p < 0.03) and burned skin (958 pg/g; p < 0.01). Hypertrophic scar samples had decreased neutral endopeptidase enzyme activity (8.8 pM MNA/hour/microg) compared with normal skin (16.3 pM MNA/hour/microg; p < 0.05). Acute burn wounds (27.9 pM MNA/hour/microg) demonstrated increased neutral endopeptidase enzyme activity (p < 0.05). CONCLUSIONS: Increased substance P concentration in hypertrophic scar correlates with histologic findings of increased nerve numbers in hypertrophic scar samples. Decreased neutral endopeptidase enzyme activity in hypertrophic scar may contribute to increased available substance P that may result in an exuberant neuroinflammatory response.

Adolescent↗

Nerve quantification in female red Duroc pig (FRDP) scar compared to human hypertrophic scar.

A significant impediment to studying hypertrophic scar is the lack of an animal model. We have confirmed similarities between scarring in the female red Duroc pig (FRDP) and human hypertrophic scar and conclude that this model warrants validation. Reports have suggested that the cutaneous nervous system may play a role in hypertrophic scar development and several studies have shown nerve density in hypertrophic scar to be increased. The purpose of this study was to further validate the FRDP model of hypertrophic scar by quantifying nerves in FRDP tissue and comparing the findings to human hypertrophic scar. Wounds of varying depth were created on the backs of two FRDP and tissue samples were harvested at 10 days, 1 month and 5 months post-wounding. Human specimens were obtained from six burn patients. Immunohistochemistry was performed and digital images were captured. Color subtractive computer-assisted image analysis was used to quantify nerve density and nerve area fraction. The results demonstrate that nerve tissue is increased in FRDP scar tissue and is quite similar to that in human hypertrophic scar and to that described in the literature. These data provide additional evidence that the FRDP model may be useful for studying hypertrophic scarring.

Adolescent↗

Is supra-Baxter resuscitation in burn patients a new phenomenon?

Baxter described the use of 4 cm3/kg/%TBSA as a guideline for fluid resuscitation after burns. However, recent studies have shown that, at the present time, patients generally receive greater than the "Baxter" formula. Pruitt has called this phenomenon "fluid creep," and it has the potential for significant consequences including abdominal and extremity compartment syndromes and severe pulmonary insults. The purpose of this paper is to determine if this supra-Baxter resuscitation is a new phenomenon. We performed a retrospective chart review with two cohorts of patients. Group 1 consisted of 11 patients admitted between 1975 and 1978 to our burn center. Group 2 consisted of 11 patients admitted to our burn center in 2000 who were matched for age, sex, and percent total body surface area burned. Group 1 received 3.6 +/- 1.1 cm3/kg/% TBSA of fluid in the first 24 h. Group 2 received 8.0 +/- 2.5 cm3/kg/% TBSA, which is 100% more than the Baxter formula. There was no difference in the median age, weight, or 24-h urine output between the two groups. Our data demonstrate that the "fluid creep" phenomenon is relatively new.

Adolescent↗