Photoactivated rose bengal mitigates a fibrotic phenotype and improves cutaneous wound healing in full-thickness injuries.

Healing of deep cutaneous wounds often results in detrimental sequelae, including painful and debilitating scars. Current therapies for full-thickness injuries that target specific phases of wound healing have moderate success; however, full resolution remains incomplete and negative consequences persist if skin homeostasis is not achieved. Photoactivated molecules can modulate cellular responses by generating reactive oxygen species and may provide a novel therapeutic option to improve wound healing. In the current study, we investigated the effects of Rose bengal (RB) dye in a preclinical model of full-thickness cutaneous injury. Monochromatic green light activates RB to generate ROS in the presence of oxygen, subsequently crosslinking collagen fibrils. In in vitro studies, we show that photoactivated RB is well tolerated by epidermal keratinocytes and dermal fibroblasts and can mitigate fibrotic signalling by downregulating collagen production. In a murine model of full-thickness injury, topically-applied and photoactivated RB closed wounds faster than control and vehicle treatments and showed significantly improved wound healing outcomes, including enhanced early granulation, better collagen organisation and increased vascularity in the presence of protracted tissue ROS. These data support an overall improved cutaneous wound healing profile after RB phototherapy and warrant further investigations into this versatile molecule.

Predictors at 6 and 12 Months for Social Participation Outcome at 24 Months in the Adult Burn Injury Population: A Burn Model System National Database Study.

OBJECTIVE: To identify clinical factors (physical and psychological symptoms and post-traumatic growth) that predict social participation outcome at 24-month after burn injury. DESIGN: A prospective cohort study based on Burn Model System National Database. SETTING: Burn Model System centers. PARTICIPANTS: 181 adult participants less than 2 years after burn injury (N=181). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Demographic and injury variables were collected at discharge. Predictor variables were assessed at 6 and 12 months: Post-Traumatic Growth Inventory Short Form (PTGI-SF), Post-Traumatic Stress Disorder Checklist Civilian Version (PCL-C), Patient-Reported Outcomes Measurement Information System (PROMIS-29) Depression, Anxiety, Sleep Disturbance, Fatigue, and Pain Interference short forms, and self-reported Heat Intolerance. Social participation was measured at 24 months using the Life Impact Burn Recovery Evaluation (LIBRE) Social Interactions and Social Activities short forms. RESULTS: Linear and multivariable regression models were used to examine predictor variables for social participation outcomes, controlling for demographic and injury variables. For LIBRE Social Interactions, significant predictors included the PCL-C total score at 6 months (ß=-0.27, P<.001) and 12 months (ß=-0.39, P<.001), and PROMIS-29 Pain Interference at 6 months (ß=-0.20, P<.01). For LIBRE Social Activities, significant predictors consisted of the PROMIS-29 Depression at 6 months (ß=-0.37, P<.001) and 12 months (ß=-0.37, P<.001), PROMIS-29 Pain Interference at 6 months (ß=-0.40, P<.001) and 12 months (ß=-0.37, P<.001), and Heat Intolerance at 12 months (ß=-4.55, P<.01). CONCLUSIONS: Post-traumatic stress and pain predicted social interactions outcomes, while depression, pain and heat intolerance predicted social activities outcomes in people with burn injury.

Outcomes of Chronically Anticoagulated Patients Undergoing Split-Thickness Skin Grafting for Diabetic Foot Ulcers.

OBJECTIVE: Split-thickness skin grafting (STSG) is commonly used for wound closure in diabetic foot ulcers (DFUs). In many cases, patients with diabetes present on long-term anticoagulation therapy. The complications associated with anticoagulants can be discouraging to surgeons considering STSG. The goal of this study was to evaluate STSG outcomes in the setting of chronic anticoagulation across a large, multicenter database. METHODS: The authors queried the TriNetX Network, which provides access to electronic medical records for more than 75 million patients, to search for patients with a history of DFUs treated with STSG. They divided those found into two groups: long-term anticoagulant use prior to grafting and no long-term anticoagulant use. After matching, the researchers evaluated outcomes following STSG after 1 month and 5 years. RESULTS: The authors identified 722 patients on chronic anticoagulation with DFUs who were treated with STSG; 446 of these patients were matched to 446 patients with no prior anticoagulation. One month following STSG, the anticoagulated group showed no significant increase in death, graft failure, or regrafting. At 5 years, there was no significant increase in mortality, graft failure, regrafting, or lower extremity amputation rates. CONCLUSIONS: Chronic anticoagulation therapy does not lead to increased short- or long-term postoperative complications such as graft failure, regrafting, or increased amputation rates following STSG for wound closure. Negative outcomes following STSG for DFUs in chronically anticoagulated individuals are minimal, and grafting should be performed without hesitation.

Preliminary Exploration of Long-Term Patient Outcomes After Tracheostomy in Burns: A Burn Model System Study.

INTRODUCTION: Upper airway management is crucial to burn care. Endotracheal intubation is often performed in the setting of inhalation injury, burns of the face and neck, or large burns requiring significant resuscitation. Tracheostomy may be necessary in patients requiring prolonged ventilatory support. This study compares long-term, patient-reported outcomes in burn patients with and without tracheostomy. MATERIALS AND METHODS: Data from the Burn Model System Database, collected from 2013 to 2020, were analyzed. Demographic and clinical data were compared between those with and without tracheostomy. The following patient-reported outcomes, collected at 6-, 12-, and 24-mo follow-up, were analyzed: Veterans RAND 12-Item Health Survey (VR-12), Satisfaction with Life, Community Integration Questionnaire, Patient-Reported Outcomes Measurement Information System 29-Item Profile Measure, employment status, and days to return to work. Regression models and propensity-matched analyses were used to assess the associations between tracheostomy and each outcome. RESULTS: Of 714 patients included in this study, 5.5% received a tracheostomy. Mixed model regression analyses demonstrated that only VR-12 Physical Component Summary scores at 24-mo follow-up were significantly worse among those requiring tracheostomy. Tracheostomy was not associated with VR-12 Mental Component Summary, Satisfaction with Life, Community Integration Questionnaire, or Patient-Reported Outcomes Measurement Information System 29-Item Profile Measure scores. Likewise, tracheostomy was not found to be independently associated with employment status or days to return to work. CONCLUSIONS: This preliminary exploration suggests that physical and psychosocial recovery, as well as the ability to regain employment, are no worse in burn patients requiring tracheostomy. Future investigations of larger scale are still needed to assess center- and provider-level influences, as well as the influences of various hallmarks of injury severity. Nonetheless, this work should better inform goals of care discussions with patients and families regarding the use of tracheostomy in burn injury.

The effects of short bouts of ergometric exercise for severely burned children in intensive care: A randomized controlled trial.

OBJECTIVE: To determine the effects of short bouts of ergometric exercises on the number of days in the burn intensive care unit (ICU), body mass, and functional ambulation. DESIGN: Multi-center, randomized controlled trial. SETTING: Burn intensive care unit. PARTICIPANTS: Children ages 7-17 with severe burns covering over 30% total body surface area (TBSA). INTERVENTION: All patients received standard of care (Control) with the experimental group receiving additional exercise with a cycle ergometer (Exercise). MAIN MEASURES: The number of days in the ICU, total weight, lean body mass (LBM), and functional ambulation were taken shortly after randomization and again within one week of the scheduled hospital discharge. Results of outcomes are expressed as median ± interquartile range (IQR), unless otherwise noted (e.g. demographics). RESULTS: Fifty-four severely burned children (n = 18 Control, n = 36 Exercise) were included. The average ± standard deviation for age was 12 ± 3 years and TBSA was 48 ± 16%. The median ± IQR ICU days for Control was 46 ± 51 days vs 31 ± 29 days for Exercise. The median total weight loss for Control was 2.2 ± 1.2 kg vs 1.8 ± 1.4 kg in Exercise. Control lost 0.75 ± 0.8 kg of LBM vs 0.46 ± 0.43 kg in Exercise. Both groups showed significant improvement in functional ambulation (p < 0.01). However, exercise did not add additional benefits. CONCLUSION: Short bouts of ergometric exercises are feasible for severely burned patients while receiving care in the ICU but did not add additional benefits.

Evaluation of Variability in Operative Efficiency in Plastic Surgery Procedures.

BACKGROUND: As the cost of healthcare rises, it is imperative to assess value delivered to patients and impact on the economic viability of institutions. We aimed to characterize plastic surgery operative time management and identified areas for efficiency improvement. METHODS: Procedures from a US academic plastic surgery division from September 2017 to August 2018 were reviewed. Times were categorized into preparation (patient in room to incision), procedure (incision to closure), exit (closure to patient exiting room), and turnover (patient out of room to next patient in room). Median and interquartile ranges were calculated. Procedures were classified by relative value units (RVUs) for comparison of procedure complexities and resources. Components were plotted against RVUs; r2 values were calculated. RESULTS: We analyzed 522 cases; 69 were excluded for missing data, primary surgeon not a plastic surgeon, emergent cases, or burn procedures; a total of 453 cases were analyzed. Median and interquartile range (in minutes) for preparation was (34, 18 minutes; 23% of total), procedure (53, 75 minutes; 36% of total), exit (30, 27 minutes; 20% of total), and turnover (30, 26 minutes; 20% of total). Normalized to RVUs, preparation demonstrated the most variability (r2 = 0.19), followed by exit (r2 = 0.38), and procedure (r2 = 0.57). Average work RVUs per month was 678.1 ± 158.7. Average work RVUs per OR hour was 7.2. CONCLUSIONS: The largest component with greatest variability was preparation for surgery in the OR. Improved efficiency by decreasing variability increases the value of healthcare delivered to patients and OR throughput.

Galunisertib Exerts Antifibrotic Effects on TGF-ß-Induced Fibroproliferative Dermal Fibroblasts.

Dermal fibroblasts in pathological scars secrete constitutively elevated levels of TGF-ß, signaling the transcription of fibrotic genes via activin-like kinase 5 (ALK5). In the present study, we examine the antifibrotic effects of galunisertib, a small-molecule inhibitor of ALK5, on fibroproliferative dermal fibroblasts in an in vitro model of wound healing. We induced fibrosis in human dermal fibroblasts with exogenous TGF-ß and performed cellular proliferation assays after treatment with varying concentrations of galunisertib. Dermal fibroblast proliferation was diminished to homeostatic levels without cytotoxicity at concentrations as high as 10 µM. An in vitro scratch assay revealed that galunisertib significantly enhanced cellular migration and in vitro wound closure beginning 24 h post-injury. A gene expression analysis demonstrated a significant attenuation of fibrotic gene expression, including collagen-1a, alpha-smooth muscle actin, fibronectin, and connective tissue growth factor, with increased expression of the antifibrotic genes MMP1 and decorin. Protein synthesis assays confirmed drug activity and corroborated the transcription findings. In summary, galunisertib simultaneously exerts antifibrotic effects on dermal fibroblasts while enhancing rates of in vitro wound closure. Galunisertib has already completed phase II clinical trials for cancer therapy with minimal adverse effects and is a promising candidate for the treatment and prevention of pathological cutaneous scars.

A Narrative Review of the History of Burn-Related Depression and Stress Reactions.

While the roots of burn care date back several millennia, recognition and treatment of psychiatric trauma has had a more contemporary journey. Our understanding of burn care has evolved largely separately from our understanding of psychiatry; however, proper care of the burn patient relies on the comprehension of both disciplines. Historically, high burn mortality rates have caused clinicians to focus on the physiological causes of burn mortality. As burn care improved in the 20th century, providers began to focus on the long-term health outcomes of burn patients, including mitigating mental health consequences of trauma. This shift coincided with advances in our understanding of psychological sequelae of trauma. Subsequently, an association between burn trauma and mental illness began to emerge. The current standard of care is the result of thousands of years of evolving practices and theories, yet our understanding of the pathophysiology of depression among survivors of severe burn injury is far from complete. By taking measure of the past, we aim to provide context and evidence for our current standards and emphasize areas for future lines of research.

Therapeutic Strategies to Reduce Burn Wound Conversion.

Burn wound conversion refers to the phenomenon whereby superficial burns that appear to retain the ability to spontaneously heal, convert later into deeper wounds in need of excision. While no current treatment can definitively stop burn wound conversion, attempts to slow tissue damage remain unsatisfactory, justifying the need for new therapeutic interventions. To attenuate burn wound conversion, various studies have targeted at least one of the molecular mechanisms underlying burn wound conversion, including ischemia, inflammation, apoptosis, autophagy, generation of reactive oxygen species, hypothermia, and wound rehydration. However, therapeutic strategies that can target various mechanisms involved in burn wound conversion are still lacking. This review highlights the pathophysiology of burn wound conversion and focuses on recent studies that have turned to the novel use of biologics such as mesenchymal stem cells, biomaterials, and immune regulators to mitigate wound conversion. Future research should investigate mechanistic pathways, side effects, safety, and efficacy of these different treatments before translation into clinical studies.

Agreement between proxy- and self-report scores on PROMIS health-related quality of life domains in pediatric burn survivors: a National Institute on Disability, Independent Living, and Rehabilitation Research Burn Model System Study.

PURPOSE: To examine agreement between pediatric burn survivor self- and caregiver proxy-report on multiple PROMIS domains and examine factors associated with differences between self- and proxy-reports. METHODS: Children 8-17 years of age and their caregivers completed PROMIS measures (physical function, depression, peer relationships, pain interference, and anger) between 6 months and 15 years after injury. Self- and proxy-report scores were compared using Wilcoxon sign rank test, Cohen's effect size, and intraclass correlation coefficients (ICC) and by agreement across severity of symptoms based on recommended cutoffs. Ordinary least squares regression analyses examined child- (self-report score, age, gender, and ethnicity) and proxy-related (relationship to child) factors associated with score differences. RESULTS: Two hundred and seventy four child-caregiver pairs completed the PROMIS measures. Mean child age was 13.0 (SD:3) years. Caregivers reported significantly worse scores than the child on physical function, pain, and anger (all p ≤ 0.01). The effect sizes were small across all domains except physical function. Similarly, ICCs were all of moderate agreement. The percentage of dyads in agreement by severity groups was high with only 5%-9% of pairs discordant. Only higher self-report score was associated (all p < 0.05) with greater differences across all domains in regression analyses. CONCLUSIONS: This study supports the use of pediatric proxy PROMIS depression, physical function, peer relationships, pain interference, and anger scales in pediatric burn patients. Although agreement was moderate to good, assessing proxy-report alone as a surrogate should only be considered when self-report is not possible or practical. Caregivers typically report slightly worse severity of symptoms than children across all domains.

A Narrative Review of the History of Skin Grafting in Burn Care.

Thermal injuries have been a phenomenon intertwined with the human condition since the dawn of our species. Autologous skin translocation, also known as skin grafting, has played an important role in burn wound management and has a rich history of its own. In fact, some of the oldest known medical texts describe ancient methods of skin translocation. In this article, we examine how skin grafting has evolved from its origins of necessity in the ancient world to the well-calibrated tool utilized in modern medicine. The popularity of skin grafting has ebbed and flowed multiple times throughout history, often suppressed for cultural, religious, pseudo-scientific, or anecdotal reasons. It was not until the 1800s, that skin grafting was widely accepted as a safe and effective treatment for wound management, and shortly thereafter for burn injuries. In the nineteenth and twentieth centuries skin grafting advanced considerably, accelerated by exponential medical progress and the occurrence of man-made disasters and global warfare. The introduction of surgical instruments specifically designed for skin grafting gave surgeons more control over the depth and consistency of harvested tissues, vastly improving outcomes. The invention of powered surgical instruments, such as the electric dermatome, reduced technical barriers for many surgeons, allowing the practice of skin grafting to be extended ubiquitously from a small group of technically gifted reconstructive surgeons to nearly all interested sub-specialists. The subsequent development of biologic and synthetic skin substitutes have been spurred onward by the clinical challenges unique to burn care: recurrent graft failure, microbial wound colonization, and limited donor site availability. These improvements have laid the framework for more advanced forms of tissue engineering including micrografts, cultured skin grafts, aerosolized skin cell application, and stem-cell impregnated dermal matrices. In this article, we will explore the convoluted journey that modern skin grafting has taken and potential future directions the procedure may yet go.

Porcine Xenograft and Epidermal Fully Synthetic Skin Substitutes in the Treatment of Partial-Thickness Burns: A Literature Review.

Background and Objectives: Porcine xenografts have been used successfully in partial thickness burn treatment for many years. Their disappearance from the market led to the search for effective and efficient alternatives. In this article, we examine the synthetic epidermal skin substitute Suprathel® as a substitute in the treatment of partial thickness burns. Materials and Methods: A systematic review following the PRISMA guidelines has been performed. Sixteen Suprathel® and 12 porcine xenograft studies could be included. Advantages and disadvantages between the treatments and the studies' primary endpoints have been investigated qualitatively and quantitatively. Results: Although Suprathel had a nearly six times larger TBSA in their studies (p < 0.001), it showed a significantly lower necessity for skin grafts (p < 0.001), and we found a significantly lower infection rate (p < 0.001) than in Porcine Xenografts. Nonetheless, no significant differences in the healing time (p = 0.67) and the number of dressing changes until complete wound healing (p = 0.139) could be found. Both products reduced pain to various degrees with the impression of a better performance of Suprathel® on a qualitative level. Porcine xenograft was not recommended for donor sites or coverage of sheet-transplanted keratinocytes, while Suprathel® was used successfully in both indications. Conclusion: The investigated parameters indicate that Suprathel® to be an effective replacement for porcine xenografts with even lower subsequent treatment rates. Suprathel® appears to be usable in an extended range of indications compared to porcine xenograft. Data heterogeneity limited conclusions from the results.

Role of anabolic testosterone agents and structured exercise to promote recovery in ICU survivors.

PURPOSE OF REVIEW: ICU survivors frequently suffer significant, prolonged physical disability. 'ICU Survivorship', or addressing quality-of-life impairments post-ICU care, is a defining challenge, and existing standards of care fail to successfully address these disabilities. We suggest addressing persistent catabolism by treatment with testosterone analogues combined with structured exercise is a promising novel intervention to improve 'ICU Survivorship'. RECENT FINDINGS: One explanation for lack of success in addressing post-ICU physical disability is most ICU patients exhibit severe testosterone deficiencies early in ICU that drives persistent catabolism despite rehabilitation efforts. Oxandrolone is an FDA-approved testosterone analogue for treating muscle weakness in ICU patients. A growing number of trials with this agent combined with structured exercise show clinical benefit, including improved physical function and safety in burns and other catabolic states. However, no trials of oxandrolone/testosterone and exercise in nonburn ICU populations have been conducted. SUMMARY: Critical illness leads to a catabolic state, including severe testosterone deficiency that persists throughout hospital stay, and results in persistent muscle weakness and physical dysfunction. The combination of an anabolic agent with adequate nutrition and structured exercise is likely essential to optimize muscle mass/strength and physical function in ICU survivors. Further research in ICU populations is needed.

Effects of Community-Based Exercise in Adults With Severe Burns: A Randomized Controlled Trial.

OBJECTIVE: To investigate the efficacy of community-based exercise programs in the rehabilitation of adult patients with burns compared with standard of care (SOC). DESIGN: Randomized controlled trial, with 2:1 randomization. SETTING: Assessments were performed in a hospital setting. The intervention was performed in a community setting. PARTICIPANTS: Adult patients (N=45) with ≥30% total body surface area burns were randomized to participate in a community-based exercise program (n=31) or SOC (n=14). Patient sampling was consecutive and referred. INTERVENTIONS: The community-based exercise program consisted of 12 weeks of exercise with a community-based trainer after hospital discharge. The SOC group did not receive exercise training. MAIN OUTCOME MEASURES: Change in lean body mass index, peak torque, and peak oxygen consumption from discharge to 12 weeks postdischarge, presented as mean ± SE. RESULTS: The community-based exercise program group showed a significant increase in peak oxygen consumption compared with SOC (community-based exercise program: Δ=7.723±1.522mL/kg/min, P=.0006; SOC: Δ=2.200±1.150mL/kg/min, P=.0765; community-based exercise program vs SOC, P=.0236). The community-based exercise program group exhibited a significant within group increase in lean body mass index (Δ=1.107±0.431kg/m2, P=.0003; SOC: Δ=1.323±0.873kg/m2, P=.2808). Both groups showed significant within-group increases in peak torque (community-based exercise program: Δ=35.645±7.566Nm, P=.0003; SOC: Δ=34.717±11.029Nm, P=.0082). No significant differences were noted between the 2 groups for lean body mass index or peak torque. CONCLUSIONS: Patients who participate in a community-based exercise program show significant improvements in cardiopulmonary fitness compared with SOC, supporting the use of a community-based exercise program as an alternative therapy to SOC in adults with severe burns.

Beclin-1-Dependent Autophagy Protects the Heart During Sepsis.

BACKGROUND: Cardiac dysfunction is a major component of sepsis-induced multiorgan failure in critical care units. Changes in cardiac autophagy and its role during sepsis pathogenesis have not been clearly defined. Targeted autophagy-based therapeutic approaches for sepsis are not yet developed. METHODS: Beclin-1-dependent autophagy in the heart during sepsis and the potential therapeutic benefit of targeting this pathway were investigated in a mouse model of lipopolysaccharide (LPS)-induced sepsis. RESULTS: LPS induced a dose-dependent increase in autophagy at low doses, followed by a decline that was in conjunction with mammalian target of rapamycin activation at high doses. Cardiac-specific overexpression of Beclin-1 promoted autophagy, suppressed mammalian target of rapamycin signaling, improved cardiac function, and alleviated inflammation and fibrosis after LPS challenge. Haplosufficiency for beclin 1 resulted in opposite effects. Beclin-1 also protected mitochondria, reduced the release of mitochondrial danger-associated molecular patterns, and promoted mitophagy via PTEN-induced putative kinase 1-Parkin but not adaptor proteins in response to LPS. Injection of a cell-permeable Tat-Beclin-1 peptide to activate autophagy improved cardiac function, attenuated inflammation, and rescued the phenotypes caused by beclin 1 deficiency in LPS-challenged mice. CONCLUSIONS: These results suggest that Beclin-1 protects the heart during sepsis and that the targeted induction of Beclin-1 signaling may have important therapeutic potential.

Pathophysiology, research challenges, and clinical management of smoke inhalation injury.

Smoke inhalation injury is a serious medical problem that increases morbidity and mortality after severe burns. However, relatively little attention has been paid to this devastating condition, and the bulk of research is limited to preclinical basic science studies. Moreover, no worldwide consensus criteria exist for its diagnosis, severity grading, and prognosis. Therapeutic approaches are highly variable depending on the country and burn centre or hospital. In this Series paper, we discuss understanding of the pathophysiology of smoke inhalation injury, the best evidence-based treatments, and challenges and future directions in diagnostics and management.

High-volume hemofiltration in adult burn patients with septic shock and acute kidney injury: a multicenter randomized controlled trial.

BACKGROUND: Sepsis and septic shock occur commonly in severe burns. Acute kidney injury (AKI) is also common and often results as a consequence of sepsis. Mortality is unacceptably high in burn patients who develop AKI requiring renal replacement therapy and is presumed to be even higher when combined with septic shock. We hypothesized that high-volume hemofiltration (HVHF) as a blood purification technique would be beneficial in this population. METHODS: We conducted a multicenter, prospective, randomized, controlled clinical trial to evaluate the impact of HVHF on the hemodynamic profile of burn patients with septic shock and AKI involving seven burn centers in the United States. Subjects randomized to the HVHF were prescribed a dose of 70 ml/kg/hour for 48 hours while control subjects were managed in standard fashion in accordance with local practices. RESULTS: During a 4-year period, a total of nine subjects were enrolled for the intervention during the ramp-in phase and 28 subjects were randomized, 14 each into the control and HVHF arms respectively. The study was terminated due to slow enrollment. Ramp-in subjects were included along with those randomized in the final analysis. Our primary endpoint, the vasopressor dependency index, decreased significantly at 48 hours compared to baseline in the HVHF group (p = 0.007) while it remained no different in the control arm. At 14 days, the multiple organ dysfunction syndrome score decreased significantly in the HVHF group when compared to the day of treatment initiation (p = 0.02). No changes in inflammatory markers were detected during the 48-hour intervention period. No significant difference in survival was detected. No differences in adverse events were noted between the groups. CONCLUSIONS: HVHF was effective in reversing shock and improving organ function in burn patients with septic shock and AKI, and appears safe. Whether reversal of shock in these patients can improve survival is yet to be determined. TRIAL REGISTRATION: Clinicaltrials.gov NCT01213914 . Registered 30 September 2010.

Adult obese mice suffer from chronic secondary brain injury after mild TBI.

BACKGROUND: A traumatic brain injury (TBI) event is a devastating injury to the brain that may result in heightened inflammation, neurodegeneration, and subsequent cognitive and mood deficits. TBI victims with co-morbidities such as heart disease, diabetes, or obesity may be more vulnerable to the secondary brain injury that follows the initial insult. Compared to lean individuals, obese subjects tend to have worse clinical outcomes and higher mortality rates after trauma. METHODS: To elucidate whether obesity predisposes individuals to worse outcomes after TBI, we subjected adult lean and obese male/female mice to a mild TBI. The injury was administered using a controlled skull impact (CSI) device. Lean or obese 6-month-old C57 BL/6 mice were subjected once to a mild TBI. Additionally, at day 30 after injury, both the lean and obese mice were tested for increased anxiety using the open field test. RESULTS: At day 30 after TBI, compared to the lean mice, we found heightened microglial (MG) activation in the cerebral cortex, corpus callosum, and hypothalamus. Another compelling finding was that, compared to the non-injured obese male control mice, the obese TBI mice had a decrease in the rate of weight gain and serum corticosterone levels at day 30 after injury. Additionally, the injured obese mice displayed higher levels of anxiety as determined by a significant decrease in time spent in the non-peripheral zones in the open field test. In contrast to the obese males, the obese female mice did not exhibit increases in the number of active MG in the brain, changes in weight gain/corticosterone levels, or increased anxiety at day 30 after TBI. CONCLUSIONS: The data presented here suggests that obese mice have worse outcomes compared to lean mice after mild TBI. Also, the obese males have worse outcomes than the injured female mice. This data may explain the sequela of chronic secondary brain injury in obese adults after a single mild TBI. Also, this report may help shape how the overweight/obese populations are monitored over the days and months following a TBI.

Severe burn increased skeletal muscle loss in mdx mutant mice.

BACKGROUND: Severe burn causes muscle mass loss and atrophy. The balance between muscle cell death and growth maintains tissue homeostasis. We hypothesize that preexisting cellular structural defects will exacerbate skeletal muscle mass loss after burn. Using a Duchenne muscular dystrophy (mdx) mutant mouse, we investigated whether severe burn caused more damage in skeletal muscle with preexisting muscle disease. METHODS: The mdx mice and wild-type (WT) mice received 25% total body surface area scald burn. Gastrocnemius (GM), tibialis anterior, and gluteus muscles were obtained at days 1 and 3 after burn. GM muscle function was measured on day 3. Animals without burn served as controls. RESULTS: Wet tissue weight significantly decreased in tibialis anterior and gluteus in both mdx and WT mice after burn (P < 0.05). The ratio of muscle to body weight decreased in mdx mutant mice (P < 0.05) but not WT. Isometric force was significantly lower in mdx GM, and this difference persisted after burn (P < 0.05). Caspase-3 activity increased significantly after burn in both the groups, whereas HMGB1 expression was higher in burn mdx mice (P < 0.05). Proliferating cell nuclear antigen decreased significantly in mdx mice (P < 0.05). Myogenic markers pax7, myoD, and myogenin increased after burn in both the groups and were higher in mdx mice (P < 0.05). CONCLUSIONS: More muscle loss occurred in response to severe burn in mdx mutant mice. Cell turnover in mdx mice after burn is differed from WT. Although markers of myogenic activation are elevated in mdx mutant mice, the underlying muscle pathophysiology is less tolerant of traumatic injury.

Comprehensive method to predict and quantify scald burns from beverage spills.

A comprehensive study was performed to quantify the risk of burns from hot beverage spills. The study was comprised of three parts. First, experiments were carried out to measure the cooling rates of beverages in a room-temperature environment by natural convection and thermal radiation. The experiments accounted for different beverage volumes, initial temperatures, cooling period between the time of service and the spill, the material which comprised the cup, the presence or absence of a cap and the presence or absence of an insulating corrugated paper sleeve. Among this list, the parameters which most influenced the temperature variation was the presence or absence of a cover or cap, the volume of the beverage and the duration of the cooling period. The second step was a series of experiments that provided temperatures at the surface of skin or skin surrogate after a spill. The experiments incorporated a single layer of cotton clothing and the exposure duration was 30 s. The outcomes of the experiments were used as input to a numerical model which calculated the temperature distribution and burn depth within tissue. Last was the implementation of the numerical model and a catalogue of burn predictions for various beverage volumes, beverage service temperatures, and durations between beverage service and spill. It is hoped that this catalogue can be used by both beverage industries and consumers to reduce the threat of burn injuries. It can also be used by treating medical professionals who can quickly estimate burn depths following a spill incident.