Fibronectin-derived Epiviosamines enhance PDGF-BB-stimulated human dermal fibroblast migration in vitro and granulation tissue formation in vivo.

Fibronectin (FN) is a multimodular glycoprotein that is a critical component of the extracellular matrix (ECM) anlage during embryogenesis, morphogenesis, and wound repair. Our laboratory has previously described a family of FN-derived peptides collectively called "epiviosamines" that enhance platelet-derived growth factor-BB (PDGF-BB)-driven tissue cell survival, speed burn healing, and reduce scarring. In this study, we used an agarose drop outmigration assay to report that epiviosamines can enhance PDGF-BB-stimulated adult human dermal fibroblast (AHDF) outmigration in a dose-dependent manner. Furthermore, these peptides can, when delivered topically, stimulate granulation tissue formation in vivo. A thiol-derivatized hyaluronan hydrogel cross-linked with polyethyleneglycol diacrylate (PEGDA) was used to topically deliver a cyclized epiviosamine: cP12 and a cyclized engineered variant of cP12 termed cNP8 to porcine, full-thickness, excisional wounds. Both cP12 and cNP8 exhibited dose-dependent increases in granulation tissue formation at day 4, with 600 µM cNP8 significantly enhancing new granulation tissue compared to vehicle alone. In contrast to previous studies, this study suggests that epiviosamines can be used to increase granulation tissue formation without an exogenous supply of PDGF-BB or any cell-binding peptides. Thus, epiviosamine may be useful topically to increase granulation tissue formation in acute wounds.

Predictive value of quick SOFA and revised Baux scores in burn patients.

Several scoring systems, such as the Baux score, help predict outcomes in burn patients. The quick Sequential Organ Failure Assessment (qSOFA) score (composed of a respiratory rate of 22/min or greater, systolic blood pressure of 100 mmHg or less, and altered mental status) is a new bedside index proposed to help identify patients with suspected infection at risk of complications. We hypothesized that qSOFA scores would be associated with in-hospital mortality, ICU admission, and length of stay (LOS) in patients with burns. We performed a retrospective review of all burn patients admitted between January 2010-March 2017 at an academic, suburban, hospital with a regional burn center. qSOFA scores were calculated as 1 point each for GCS<15, RR≥22, and SBP≤100. A qSOFA value of>2 was considered high risk. Revised Baux (rBaux) scores were calculated as age +%TBSA burned +17 (if inhalation injury). A rBaux score >140 was considered high risk. Univariate, multivariate and receiver operating characteristics analyses were performed to compare qSOFA and rBaux scores. There were 1039 burn admissions during the study period. Mean age was 30 ± 24 years, 66% were male. Mean TBSA was 10 ± 12%, mean injury severity score was 5 ± 8. Mean hospital LOS was 8 ± 24 days, 22 patients (2.1%) died. qSOFA scores were associated with mortality and ICU admission. Of all patients, 80 were high risk by qSOFA and 7 by Baux scores. ROC characteristics of qSOFA and Baux scores for predicting death were sensitivity 36% vs. 32%, specificity 94% vs. 100%, PPV 13% vs. 100%, and NPV 98% vs. 99% respectively. The AUC for qSOFA (0.68 [95% CI, 0.54-0.81]) was lower than for Baux (0.99 [95%CI, 0.99-1.00]). Youden's index identified an optimal cutoff of 85 on the Baux score yielding sensitivity 100%, specificity 94%, PPV 27%, and NPV 100% for mortality. Our results indicate that while qSOFA scores were associated with outcomes, a rBaux score had greater predictive value. The optimal rBaux score for predicting all mortality and ICU admission was 85.

The association of patient and burn characteristics with itching and pain severity.

INTRODUCTION: Itch after burn injury causes significant distress to patients and can hamper functional recovery. Itching can persist on a time scale ranging from several weeks to even years after injury. In this study, we sought to determine predictors of itching after burn injury. METHODS: We compared itch and pain severity among patients included in a burn registry at a level 1 trauma center. Both itch and pain severity was based on a 5-point scale. ANOVA, chi-squared, and multivariate analyses were performed to determine predictors of itch and pain severity. RESULTS: Of the 1159 patients enrolled in the registry, 58% were male and 42% female, with a median age (IQR) of 27 (8-47) years. Most patients were diagnosed with 2nd degree superficial (41%) or deep (43%) burns. Upper extremities were the most common location of burn injury (59%), followed by lower extremities (31%), trunk (22%), and face/neck (20%). More than half (53%) of enrolled patients reported itching, ranging from minimal (19%) to severe (7%) itching. Multivariate analyses revealed age, sex (female), extent of burn injuries, and location (face/neck) to be predictors of itch after burn. Predictors of pain after burn were slightly different: age, extent of burn, and depth of burn. CONCLUSION: Pain and itch after burn injuries are predicted by slightly different variables, presumably secondary to different underlying mechanisms. We conclude that age, sex (female), extent of burn injuries (total body surface area %), and injuries to the face/neck predict itching of greater severity. Patients with burn injuries that match these parameters would require greater care and closer follow up to reduce itching after healing.

Fibronectin interaction with growth factors in the context of general ways extracellular matrix molecules regulate growth factor signaling.

Wound healing is a complex cascade of molecular events centered on the extracellular matrix (ECM). Early research viewed ECM in wounds as a simple scaffold for repair. Subsequently, this perception was extended to providing cells with discrete surface adhesion sites and then to providing a reservoir for growth factors (GF). However, over the past decade, research has revealed that ECM interactions with GF are far more complex and exquisite than previously thought. Chief among ECM components during the early phases of wound healing is a ~250kDa glycoprotein, fibronectin (FN). This review outlines ways in which FN interacts with GF as a model for studying ECM-GF interactions. Additionally, we present evidence to suggest that FN contains bioactive peptides that enhance or bias GF activity and thereby can be used as pharmacologic interventions for wound healing.

Comparison of Pain Severity and Management in Burn and Nonburn Trauma Patients.

Burn injuries are generally considered to be among the most painful. However, there is little evidence to support this. It is also unknown if pain management in burn patients differs from patients with other sources of pain. We compared pain severity among patients presenting to emergency departments (EDs) across the United States with burn and nonburn injuries using data generated from the National Hospital Ambulatory Care Survey. Multivariate analyses was performed to determine the association between predictor variables and pain severity as well as pain management in the ED. Of the estimated 527 million ED visits between 2010 and 2013, 2.1 million were due to burns and 128 million were due to nonburn trauma. Mean (SE) initial pain scores by patient group were burns 6.3 (0.27), nonburn trauma 5.4 (0.04), and nontrauma 4.8 (0.04), P < .001. Mean (95% confidence interval) pain scores by specific type of injury were burns 6.4 (5.9-6.9), fractures 6.7 (6.6-6.9), dislocations 6.7(6.3-7.1), and sprains/strains 6.8 (6.7-6.9), P < .001. Pain scores were higher for males and increased with age. Adjusted for age and gender, burns had the smallest effect of all types of injuries on pain score except for open wounds, contusions, and crush injuries. Patients with fractures and dislocations were more likely to receive an opioid than burn patients after adjusting for pain severity. We conclude that pain severity due to burns is no greater than due to dislocations, fractures, and sprains/strains and that burn patients are less likely to receive opioid and nonopioid analgesics than fractures and dislocations.

ArF excimer laser debrides burns without destruction of viable tissue: A pilot study.

INTRODUCTION: Recent evidence indicates that early removal of eschar by tangential debridement can promote healing. Laser debridement can be used for debridement of areas that prove challenging for debridement using tangential excision. In particular, irradiation with an ArF excimer laser ablates desiccated eschar and is self-terminating, preserving hydrated or viable tissue. METHODS: Thermal burns were created on the flanks of two outbred, female Yorkshire pigs using aluminum bars heated to 70°C and applied for different lengths of time. Three days after injury, burns were debrided using an ArF excimer laser (193nm). Tissue was harvested immediately after debridement and 7days after debridement (10days after burn). RESULTS: Data from a pilot study demonstrates that ArF excimer laser irradiation removes burn eschar and promotes healing at 10days after burn. ArF excimer laser debridement is self-terminating and preserves underlying and adjacent perfused tissue. Potentially, this modality would be ideal for the complex curvilinear structures of the body.

Forward-looking infrared imaging predicts ultimate burn depth in a porcine vertical injury progression model.

INTRODUCTION: Current methods of assessing burn depth are limited and are primarily based on visual assessments by burn surgeons. This technique has been shown to have only 60% accuracy and a more accurate, simple, noninvasive method is needed to determine burn wound depth. Forward-looking infrared (FLIR) thermography is both noninvasive and user-friendly with the potential to rapidly assess burn depth. The purpose of this paper is to determine if early changes in burn temperature (first 3 days) can be a predictor of burn depth as assessed by vertical scarring 28 days after injury. METHODS: While under general anesthesia, 20 burns were created on the backs of two female Yorkshire swine using a 2.5cm×2.5cm×7.5cm, 150g aluminum bar, for a total of 40 burns. FLIR imaging was performed at both early (1, 2 and 3 days) and late (7, 10, 14, 17, 21, 24 and 28 days) time points. Burns were imaged from a height of 12 inches from the skin surface. FLIR ExaminIR(©) software was used to examine the infrared thermographs. One hundred temperature points from burn edge to edge across the center of the burn were collected for each burn at all time points and were exported as a comma-separated values (CSV) file. The CSV file was processed and analyzed using a MATLAB program. The temperature profiles through the center of the burns generated parabola-like curves. The lowest temperature (temperature minimum) and a line midway between the temperature minimum and ambient skin temperature at the burn edges was defined and the area of the curve calculated (the "temperature half-area"). RESULTS: Half-area values 2 days after burn had higher correlations with scar depth than did the minimum temperatures. However, burns that became warmer from 1 day to 2 days after injury had a lower scar depth then burns that became cooler and this trend was best predicted by temperature minima. When data were analyzed as a diagnostic test for sensitivity and specificity using >3mm scarring, i.e. a full-thickness burn, as a clinically relevant criterion standard, temperature minima at 2 days after burn was found to be the most sensitive and specific test. CONCLUSIONS: FLIR imaging is a fast and simple tool that has been shown to predict burn wound outcome in a porcine vertical injury progression model. Data showed that more severe burn wounds get cooler between 1 and 2 days after burn. We found four analytic methods of FLIR images that were predictive of burn progression at 1 and 2 days after burn; however, temperature minima 2 days after burn appeared to be the best predictive test for injury progression to a full-thickness burn. Although these results must be validated in clinical studies, FLIR imaging has the potential to aid clinicians in assessing burn severity and thereby assisting in burn wound management.