The impact of electrical injuries on long-term outcomes: A Burn Model System National Database study.

INTRODUCTION: Electrical injuries exhibit significant acute and long-term sequelae. Amputation and neurological deficits are common in electrical injury survivors. There is a paucity of information on the long-term outcomes of this population. Therefore, this study examines the long-term outcomes of electrical injuries by comparing them to fire/flame injuries. METHODS: Data from the Burn Model System National Database collected between 1996 and 2015 was examined. Demographic and clinical characteristics for adult burn survivors with electrical and fire/flame injuries were compared. Satisfaction With Life Scale (SWLS), Short Form-12 Physical Composite Score (SF-12 PCS), Short Form-12 Mental Composite Score (SF-12 MCS), and employment status were examined at 24 months post-injury. Linear and logistic regression models were used to assess differences in outcome measures between groups, controlling for demographic and clinical variables. RESULTS: A total of 1147 adult burn survivors (111 with electrical injuries; 1036 with fire/flame injuries) were included in this study. Persons with electrical injuries were more likely to be male and injured at work (p<0.001). SF-12 PCS scores were significantly worse for survivors with electrical injuries at 24 months post-injury than survivors with fire/flame injuries (p<0.01). Those with electrical injuries were nearly half as likely to be employed at 24 months post-injury than those with fire/flame injuries (p=0.002). There were no significant differences in SWLS and SF-12 MCS between groups. CONCLUSIONS: Adult survivors with electrical injuries reported worse physical health and were less likely to be employed at 24 months post-injury compared to survivors with fire/flame injuries. A more detailed understanding of return to work barriers and work accommodations is merited for the electrical injury population. Furthermore, the results of this study should inform future resource allocation for the physical health and employment needs of this population.

Prospective observational study comparing burn surgeons' estimations of wound healing after skin grafting to photo-assisted methods.

INTRODUCTION: Appropriate graft healing after split-thickness skin graft and early recognition of complications (graft loss) are critical to burn patient management. Larger mesh ratio expansions and Meek micrografting may pose a greater challenge in estimating the percentage of wound healing. This study looks at the reliability of photograph assessments and the concordance of bedside evaluation to photograph assessments of wound healing after skin grafting. METHODS: Three assessment methods for percentage of wound healing after skin Grafting were assessed: (1) clinicians' bedside rating, (2) clinician assessment of high-definition photographs, and (3) digital image analysis through color subtraction using Adobe Photoshop. We compared each method using a mixed-effects model on absolute agreement using intra-class correlation (ICC) and Bland Altman (BA) plots. RESULTS: Fourteen burn patients were enrolled with 38 grafted wounds (100 sites). Bedside assessments had a mean ICC of 0.64 (compared to digital image analysis) and 0.69 (compared to photo assessment), with a wide range on BA-plots. Inter-rater reliability of photo assessment was excellent (0.96) among six clinicians. Repeated photo-assisted assessments had good intra-rater reliability (ICC: photo assessment: 0.88; digital analysis: 0.97). CONCLUSIONS: Bedside wound healing assessments show variability; photograph documentation of sequential wound progression could supplement active clinical management or studies for more reliable assessments.

Head and neck burns are associated with long-term patient-reported dissatisfaction with appearance: A Burn Model System National Database study.

INTRODUCTION: Burns affecting the head and neck (H&N) can lead to significant changes in appearance. It is postulated that such injuries have a negative impact on patients' social functioning, quality of life, physical health, and satisfaction with appearance, but there has been little investigation of these effects using patient reported outcome measures. This study evaluates the effect of H&N burns on long-term patient reported outcomes compared to patients who sustained burns to other areas. METHODS: Data from the National Institute on Disability, Independent Living, and Rehabilitation Research Burn Model System National Database collected between 1996 and 2015 were used to investigate differences in outcomes between those with and without H&N burns. Demographic and clinical characteristics for adult burn survivors with and without H&N burns were compared. The following patient-reported outcome measures, collected at 6, 12, and 24 months after injury, were examined: satisfaction with life (SWL), community integration questionnaire (CIQ), satisfaction with appearance (SWAP), short form-12 physical component score (SF-12 PCS), and short form-12 mental component score (SF-12 MCS). Mixed regression model analyses were used to examine the associations between H&N burns and each outcome measure, controlling for medical and demographic characteristics. RESULTS: A total of 697 adults (373 with H&N burns; 324 without H&N burns) were included in the analyses. Over 75% of H&N injuries resulted from a fire/flame burn and those with H&N burns had significantly larger burn size (p<0.001). In the mixed model regression analyses, SWAP and SF-12 MCS were significantly worse for adults with H&N burns compared to those with non-H&N burns (p<0.01). There were no significant differences between SWL, CIQ, and SF-12 PCS. CONCLUSIONS: Survivors with H&N burns demonstrated community integration, physical health, and satisfaction with life outcomes similar to those of survivors with non-H&N burns. Scores in these domains improved over time. However, survivors with H&N burns demonstrated worse satisfaction with their appearance. These results suggest that strategies to address satisfaction with appearance, such as reconstructive surgery, cognitive behavior therapy, and social skills training, are an area of need for survivors with H&N burns.

12-Year within-wound study of the effectiveness of custom pressure garment therapy.

Pressure garment therapy is standard of care for prevention and treatment of hypertrophic scarring after burn injury. Nevertheless there is little objective data that confirms effectiveness. The purpose of this study was to determine the effectiveness of pressure garment therapy with objective data obtained with a randomized within-wound comparison. We enrolled consecutive patients with forearm injuries over a 12-year period. The subjects wore custom garments with normal and low compression randomized to either the proximal or distal zones. Hardness, color and thickness of wounds were objectively measured using appropriate devices; clinical appearance was measured by a panel masked to the identity of the pressure treated area. Wounds treated with normal compression were significantly softer, thinner, and had improved clinical appearance. There was no interaction of any effect with patient ethnicity. However, these findings were clinically evident only with moderate to severe scarring. We conclude that pressure garment therapy is effective, but that the clinical benefit is restricted to those patients with moderate or severe scarring.

The methamphetamine burn patient.

Early aggressive fluid resuscitation has significantly decreased the morbidity and mortality associated with volume losses from large burns. Although most patients are adequately resuscitated using the Parkland formula, we noted increased fluid requirements for shock resuscitation in patients involved in methamphetamine laboratory explosions. Because predominant users are young healthy individuals in their 20s and 30s, we had not anticipated burn shock resuscitation failures in this patient group. We reviewed our experience with burn patients with documented methamphetamine use to determine whether this patient group presents new dilemmas to the burn surgeon. A 2-year retrospective study of 30 patients (15 methamphetamine users, 15 controls) revealed that the methamphetamine burn patient requires two to three times the standard Parkland formula resuscitation. In this study, methamphetamine burns larger than 40% TBSA had a 100% mortality.

Current management of purpura fulminans: a multicenter study.

Seven burn centers performed a 10-yr retrospective chart review of patients diagnosed with purpura fulminans. Patient demographics, etiology, presentation, medical and surgical treatment, and outcome were reviewed. A total of 70 patients were identified. Mean patient age was 13 yr. Neisseria meningitidis was the most common etiologic agent in infants and adolescents whereas Streptococcus commonly afflicted the adult population. Acute management consisted of antibiotic administration, volume resuscitation, ventilatory and inotropic support, with occasional use of corticosteroids (38%) and protein C replacement (9%). Full-thickness skin and soft-tissue necrosis was extensive, requiring skin grafting and amputations in 90% of the patients. One fourth of the patients required amputations of all extremities. Fasciotomies when performed early appeared to limit the level of amputation in 6 of 14 patients. Therefore, fasciotomies during the initial management of these patients may reduce the depth of soft-tissue involvement and the extent of amputations.

Dermatome setting for autografts to cover INTEGRA.

Using the INTEGRA Dermal Regeneration Template requires the outer silastic layer to be replaced with an autograft. We followed the manufacturer's directions for epidermal autografting and frequently obtained shredded, useless grafts, therefore, it seemed important to determine the proper dermatome setting. We evaluated dermatome settings from 0.002 to 0.012 inches. First, with feeler gauges, we verified the dermatome settings. Second, we harvested skin at various dermatome settings and measured the thickness histologically. We found that 1) the dermatome settings are reasonably accurate; 2) harvesting useful sheets at 0.002 and 0.004 inches is virtually impossible; 3) the variability of histologic graft thickness is enormous; and 4) a dermatome setting of 0.006 inches yields useful grafts. We no longer use the term epidermal autografting but rather ultrathin split-thickness grafting. To harvest these grafts, we now merely set the dermatome to 0.006 inches and make whatever midcourse corrections are necessary to obtain translucent grafts.

Cones of skin occur where hypertrophic scar occurs.

Hypertrophic scarring is devastating for the patient, however the pathophysiology and treatment remain unknown after decades of research. The process follows deep dermal injury, occurs only on certain body parts, does not occur in the early fetus or in animals, and is a localized event. This suggests that an anatomic structure in human, deep dermis may be involved. The dermis is a matrix perforated by cones containing many structures including skin appendages and fat domes. We hypothesized that studying the cones might reveal a structure related to scarring. We examined tangential wounds from various body parts on human cadavers along with skin histology from various human body parts, the early fetus, partial thickness burns, hypertrophic scars, and two other species-rats and rabbits. We found that the cones may in fact be the structure. They exist where hypertrophic scar occurs-cheek, neck, chest, abdomen, back, buttock, arm, forearm, dorsal hand, thigh, leg, dorsal foot, helix and ear lobe. They do not exist where hypertrophic scar does not occur-scalp, forehead, concha, eyelid, palm, early fetus, and in rat, or rabbit. It also became apparent that the cones have been omitted from most considerations of skin histology. We suggest that the cones need to be studied in relation to hypertrophic scarring and restored to skin diagrams.

Color subtractive-computer-assisted image analysis for quantification of cutaneous nerves in a diabetic mouse model.

Immunohistochemistry (IHC) is a valuable tool for labeling structures in tissue samples. Quantification of immunolabeled structures using traditional approaches has proved to be difficult. Manual counts of IHC-stained structures are inherently biased, require multiple observers, and generate qualitative data. Stereological methods provide accurate quantification but are complex and labor-intensive when staining must be compared among large numbers of samples. In an effort to quickly, objectively, and reproducibly quantify cutaneous innervation in a large number of counterstained tissue sections, we developed a color subtractive-computer-assisted image analysis (CS-CAIA) system. To develop and test the CS-CAIA method, tissue sections of diabetic (db/db) mouse skin and their wild-type (db/-) littermates were stained by IHC for the neural marker PGP 9.5. The brown-red PGP 9.5 peroxidase stain was colorimetrically isolated through a scripted process of color background removal. The remaining stain was thresholded and binarized for computer determination of nerve profile counts (number of stained regions), area fraction (total area of nerve profiles per unit area of tissue), and area density (total number of nerve profiles per unit area of tissue). Using CS-CAIA, epidermal nerve profile counts, area fraction, and area density were significantly lower in db/db compared to db/- mice.

Comparison of normal human skin gene expression using cDNA microarrays.

Perturbations in normal wound healing may be traced to perturbations in gene expression in uninjured skin. In order to decipher normal and abnormal genetic responses to cutaneous injury, baseline gene expression in uninjured skin must first be defined. There is little data on gene expression profiles of normal human skin, i.e., which genes tend to be variable in expression and which tend to remain comparable. Therefore this study was designed to determine the degree of variability in human skin mRNA expression. Samples of normal skin were obtained from 9 healthy females undergoing breast reduction surgery. RNA was extracted, reverse transcribed into radiolabeled cDNA and hybridized onto cDNA microarrays of approximately 4400 genes. Gene expression intensities from the 9 samples were normalized and compared as a ratio of highest/lowest expression intensity. Deviation greater than 2 standard deviations from the mean of each gene was used as a cut-off. Seventy-one genes (1.7%) were substantially variable in their expression. These included genes coding for transport proteins, gene transcription, cell signaling proteins, and cell surface proteins. We found minimal variability in the matrix genes, growth factor genes and other groups of genes that are the most often studied in wound healing research. A small but definite variability in gene expression across 9 samples of clinically comparable specimens of normal skin was detected. This is in keeping with clinical observations of the variability in normal skin across individuals. These data provide high-throughput comparison of normal skin gene expression and suggest new molecules that may be studied in skin biology and perhaps, wound repair.

Toxic epidermal necrolysis (TEN) in elderly patients.

Toxic epidermal necrolysis (TEN) is a severe exfoliative disease of the skin and mucous membranes that results in high mortality. As the elderly population increases, the number of elderly patients with TEN can also be expected to increase. Elderly patients with comparably sized burn wounds usually have a poor prognosis. Our purpose was to determine whether elderly TEN patients exhibit similarly high mortality. A retrospective review was conducted of 52 patients treated for TEN from October 1991 through September 1998. Eleven patients were older than 65 years. All patients were treated according to our TEN protocol. Eight of 11 patients recovered, and 3 died. The mean total body surface area (TBSA) involvement for the patients who recovered was 24%, compared with 66% for the nonsurvivors. The survival rate for elderly patients (73%) compares well with that for those younger than 65 years (89%). Therefore, we propose that we should be aggressive in treating elderly patients with TEN.

Prospective trial of thick vs standard split-thickness skin grafts in burns of the hand.

For best function and appearance, thick skin grafts for hands are generally preferred to thinner grafts. But how thick is thick enough? This prospective randomized trial was designed to compare 0.015-inch skin grafts for burned hands to hand grafts that are 0.025 inches thick. Consecutive patients receiving skin grafts to hands were randomized to have sheet grafts using donor sites of 0.015-inch or 0.025-inch thickness. To prevent delayed healing and potential hypertrophic scarring, the thick graft donor sites were grafted with 0.008-inch grafts. There were no significant differences in range of motion, final appearance, or patient satisfaction between the two groups at 1 year. There were problems with donor site healing in both groups. We recommend that hand grafts for adults be at least 0.015 inches thick but do not see an advantage to the use of very thick (0.025-inch) grafts, even with thin split-thickness skin grafts to the donor site.

Time off work and return to work rates after burns: systematic review of the literature and a large two-center series.

The literature on time off work and return to work after burns is incomplete. This study addresses this and includes a systematic literature review and two-center series. The literature was searched from 1966 through October 2000. Two-center data were collected on 363 adults employed outside of the home at injury. Data on employment, general demographics, and burn demographics were collected. The literature search found only 10 manuscripts with objective data, with a mean time off work of 10 weeks and %TBSA as the most important predictor of time off work. The mean time off work for those who returned to work by 24 months was 17 weeks and correlated with %TBSA. The probability of returning to work was reduced by a psychiatric history and extremity burns and was inversely related to %TBSA. In the two-center study, 66% and 90% of survivors had returned to work at 6 and 24 months post-burn. However, in the University of Washington subset of the data, only 37% had returned to the same job with the same employer without accommodations at 24 months, indicating that job disruption is considerable. The impact of burns on work is significant.

Rates, trends, and severity of depression after burn injuries.

It is commonly assumed that patients hospitalized for burn treatment will experience some level of depression. However, little is known about the trends in severity of depression over time. The purpose of this study was to determine the rates and severity of depression over a 2-year period. The Beck Depression Inventory was administered at 1 month (N = 151), 1 year (N = 130), and 2 years (N = 125) after discharge. At 1 month, 54% of patients showed symptoms of moderate to severe depression, and at 2 years, 43% of the patients responding still reported moderate to severe depression. The average correlation between scores over time was high. Women had higher depression scores than men at each time period. An interaction between gender and having a head or neck injury was also observed at 1 month and 1 year after discharge. Results suggest that routine outpatient screening for depression is warranted.

Dexter: a tool to facilitate impairment ratings.

Calculating impairment in burn patients is crucial to understanding outcome. However, it is rarely reported after burns, presumably because the process of calculating impairment ratings is complicated and tedious. Computerized systems have been developed that facilitate the process, but it has not been established in burn patients that these systems reduce the time required to calculate impairment. We evaluated the Dexter Evaluation and Therapy System by Cedaron Medical Inc (Davis, CA). A sample of 10 manually recorded ratings was compared with 10 performed on the Dexter. Mean time for the manual technique was 65 +/- 35 minutes versus 37 +/- 13 minutes for the Dexter (P < .05, Mann-Whitney). The time taken to perform impairment ratings in burn survivors is significantly reduced by the use of the Dexter system. Time saving occurs primarily at three points: (1) electronic data entry directly from the measuring instruments, (2) compilation of data, and (3) rapid generation of reports.

Early gene expression profile of human skin to injury using high-density cDNA microarrays.

Disturbances in normal wound healing may be traced to perturbations in gene expression following injury. To decipher normal and abnormal genetic responses to cutaneous injury, baseline gene expression of uninjured skin and injured skin must be better defined. Our aim for this study was to determine the gene expression profile of human skin immediately following injury using cDNA microarrays. Samples of normal and injured skin were obtained from 5 healthy females undergoing breast reduction surgery. Specimens of the epidermis and dermis were obtained at 30 minutes and 1 hour after the initial injury. RNA was extracted, reverse transcribed into cDNA and hybridized onto high-density cDNA microarray membranes of 4,000 genes. At 30 minutes, injury resulted in a consistent increase (> 2x) in gene expression of 124 out of 4,000 genes (3%). These genes were primarily involved in transcription and signaling. None of the 4,000 genes were decreased (< 2x) at 30 minutes. At 1 hour only 46 out of the 4,000 genes were increased in expression (1.15%) but 264 out of 4,000 (6.6%) genes were decreased greater than 2 fold, indicating a silencing of many structural genes. We have identified several genes, namely, suppressor of cytokine signaling-1, rho HP1, and BB1, that are highly expressed after injury and may have an unappreciated role in regulating the initial inflammatory response. These data provide an initial high-throughput analysis of gene expression immediately following human skin injury and show the utility and future importance of high-throughput analysis in skin biology and wound repair.

Nerve distribution in hemangiomas depends on the proliferative state of the microvasculature.

Hemangiomas appear at birth and undergo gradual regression within several years. Recent published studies have documented increased nerve numbers in port-wine stains and intramuscular vascular tumors. The aim of this study was to establish a relationship between angiogenesis and nerve growth in lesions that undergo neovascular proliferation followed by vessel involution. Twenty-two hemangiomas and arteriovenous malformations were studied using indirect immunocytochemistry with antibodies against the nerve markers protein gene product 9.5 (PGP 9.5) and calcitonin gene-related peptide (CGRP). Nerves and vessels were counted and compared. Our results indicate that PGP 9.5(+) and CGRP(+) nerves were most numerous in growing hemangiomas and numbers were reduced in involuting hemangiomas and vascular malformations. The percentage of CGRP(+) sensory nerves was markedly increased in growing hemangiomas (45.3%) compared with involuting hemangiomas (21.2). These data indicate that hemangiomas with increasing neovascularization have increased sensory nerve growth. Sensory nerve-derived neuropeptides are known to act as endothelial cell mitogens and may contribute to the angiogenesis in these vascular tumors. Conversely, angiogenic endothelial cells may secrete mediators that promote nerve fiber growth. These results suggest that endothelial cell proliferation and sensory nerve fiber growth may be closely related.

Vitronectin deficiency is associated with increased wound fibrinolysis and decreased microvascular angiogenesis in mice.

BACKGROUND: Vitronectin has several putative functions including regulating hemostasis, cell adhesion, and cell migration. However, the targeted deletion of vitronectin in mice results in normal development and normal coagulation parameters. To determine whether vitronectin may be necessary for nondevelopmental processes, we examined the response to tissue injury in vitronectin-null mice. METHODS: We examined wound healing in control and vitronectin-null mice by healing rate, zymography, reverse zymography, and Western blots. RESULTS: We found that dermal wound healing was slightly delayed in mice lacking vitronectin. More importantly, we found extensive areas of delayed hemorrhage near the sprouting tips of microvessels between days 7 and 14, which temporally coincided with increased urokinase-type plasminogen activator and tissue-type plasminogen activator activity by zymography. Though Western blots confirmed the presence of plasminogen activator inhibitor-1 protein throughout wound repair and reverse zymograms showed decreased plasminogen activator inhibitor-1 activity between days 7 and 14. CONCLUSIONS: Loss of vitronectin in mice was associated with changes in the fibrinolytic balance, and this may have led to focal sites of delayed hemorrhage. The mechanism that resulted in decreased angiogenesis and the formation of larger blood vessels in response to tissue injury remains unknown. This study suggests that vitronectin may have several distinct functions that are not required for normal development but are manifested in response to tissue injury.

Effect of storage and preservation methods on viability in transplantable human skin allografts.

This study compared the metabolic activity of fresh skin samples to that of cadaver human skin allografts processed and stored by current tissue banking methods. We chose to use two metabolic assays as surrogate measures for viability in these grafts. Skin allografts stored either in liquid media at 4 degrees C for varying periods of time or stored by cryopreservation were quantitatively assessed for viability by tetrazolium reduction and oxygen consumption assays. These measurements were compared to viability assessments of fresh autograft skin. Human cadaver skin grafts, after procurement and just prior to further tissue bank processing, exhibited approximately 60% of the metabolic activity found in fresh skin samples obtained from living surgical donors. If allowed an overnight (18-24 h) incubation period at 37 degrees C, cadaver samples showed a recovery of their metabolic activity to 95% of that found in the autograft skin samples. When stored in liquid media at 4 degrees C, the cadaver skin declined steadily in cellular metabolic activity, arriving in less than 5 days storage at a measurement below that of cryopreserved skin. The cryopreserved skin was measured both immediately after thawing and dilution of cryoprotectant, as well as after equilibration and overnight incubation. Skin cryopreserved with dimethylsulfoxide Me(2)SO retained higher viability than glycerol cryopreserved skin. Residual concentrations of cryoprotectants were determined following typical recommendations for thawing and diluting skin allografts. The implications of these findings for transplantation and tissue banking are discussed.