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.

Effects of exercise on soleus in severe burn and muscle disuse atrophy.

BACKGROUND: Muscle loss is a sequela of severe burn and critical illness with bed rest contributing significantly to atrophy. We hypothesize that exercise will mitigate muscle loss after burn with bed rest. MATERIALS AND METHODS: Male rats were assigned to sham ambulatory (S/A), burn ambulatory (B/A), sham hindlimb unloading (S/H), or burn hindlimb unloading (B/H). Rats received a 40% scald burn or sham and were ambulatory or placed in hindlimb unloading, a model of bed rest. Half from each group performed twice daily resistance climbing. Hindlimb isometric forces were measured on day 14. RESULTS: Soleus mass and muscle function were not affected by burn alone. Mass was significantly lower in hindlimb unloading (79 versus 139 mg, P < 0.001) and no exercise (103 versus 115 mg, P < 0.01). Exercise significantly increased soleus mass in B/H (86 versus 77 mg, P < 0.01). Hindlimb unloading significantly decreased muscle force in the twitch (12 versus 31 g, P < 0.001), tetanic (55 versus 148 g, P < 0.001), and specific tetanic measurements (12 versus 22 N/cm(2), P < 0.001). Effects of exercise on force depended on other factors. In B/H, exercise significantly increased twitch (14 versus 8 g, P < 0.05) and specific tetanic force (14 versus 7 N/cm(2), P < 0.01). Fatigue index was lower in ambulatory (55%) and exercise (52%) versus hindlimb (69%, P = 0.03) and no exercise (73%, P = 0.002). CONCLUSIONS: Hindlimb unloading is a significant factor in muscle atrophy. Exercise increased the soleus muscle mass, twitch, and specific force in this model. However, the fatigue index decreased with exercise in all groups. This suggests exercise contributes to functional muscle change in this model of disuse and critical illness.

Exercise Altered the Skeletal Muscle MicroRNAs and Gene Expression Profiles in Burn Rats With Hindlimb Unloading.

This study investigated microRNA and target gene profiles under different conditions of burn, bed rest, and exercise training. Male Sprague-Dawley rats (n = 48) were assigned to sham ambulatory, sham hindlimb unloading, burn ambulatory, or burn plus hindlimb unloading groups. Rats received a 40% TBSA scald burn or sham treatments and were ambulatory or hindlimb unloaded. Rats were further assigned to exercise or no exercise. Plantaris tissues were harvested on day 14 and pooled to analyze for microRNA and gene expression profiles. Compared with the sham ambulatory-no exercise group, 73, 79, and 80 microRNAs were altered 2-fold in the burn ambulatory, sham hindlimb unloading, and burn hindlimb unloading groups, all with no exercise, respectively. More than 70% of microRNAs were upregulated in response to burn and hindlimb unloading, whereas 60% microRNA of the profile decreased in hindlimb unloaded burn rats with exercise training. MiR-182 was the most affected in rat muscle. Gene ontology biological process and pathway analysis showed that the oxidative stress pathway was most stimulated in the hindlimb unloaded burn rats; while in response to exercise training, all genes in related pathways such as hypermetabolic, inflammation, and blood coagulation were alleviated. MicroRNAs and transcript gene profiles were altered in burn and hindlimb unloading groups, with additive effects on hindlimb unloaded burn rats. The altered genes' signal pathways were associated with muscle mass loss and function impairment. Muscle improvement with exercise training was observed in gene levels with microRNA alterations as well.

The Effect of Burn Center Volume on Mortality in a Pediatric Population: An Analysis of the National Burn Repository.

The effect of burn center volume on mortality has been demonstrated in adults. The authors sought to evaluate whether such a relationship existed in burned children. The National Burn Repository, a voluntary registry sponsored by the American Burn Association, was queried for all data points on patients aged 18 years or less and treated from 2002 to 2011. Facilities were divided into quartiles based on average annual burn volume. Demographics and clinical characteristics were compared across groups, and univariate and multivariate logistic regressions were performed to evaluate relationships between facility volume, patient characteristics, and mortality. The authors analyzed 38,234 patients admitted to 88 unique facilities. Children under age 4 years or with larger burns were more likely to be managed at high-volume and very high-volume centers (57.12 and 53.41%, respectively). Overall mortality was low (0.85%). Comparing mortality across quartiles demonstrated improved unadjusted mortality rates at the low- and high-volume centers compared with the medium-volume and very high-volume centers although univariate logistic regression did not find a significant relationship. However, multivariate analysis identified burn center volume as a significant predictor of decreased mortality after controlling for patient characteristics including age, mechanism of injury, burn size, and presence of inhalation injury. Mortality among pediatric burn patients is low and was primarily related to patient and injury characteristics, such as burn size, inhalation injury, and burn cause. Average annual admission rate had a significant but small effect on mortality when injury characteristics were considered.

Epidemiology and outcomes of pediatric burns over 35 years at Parkland Hospital.

BACKGROUND: Since opening its doors in 1962, the Parkland Burn Center has played an important role in improving the care of burned children through basic and clinical research while also sponsoring community prevention programs. The aim of our study was to retrospectively analyze the characteristics and outcomes of pediatric burns at a single institution over 35 years. STUDY DESIGN: The institutional burn database, which contains data from January 1974 until August 2010, was retrospectively reviewed. Patients older than 18 years of age were excluded. Patient age, cause of burn, total body surface area (TBSA), depth of burn, and patient outcomes were collected. Demographics were compared with regional census data. RESULTS: Over 35 years, 5748 pediatric patients were admitted with a thermal injury. Males comprised roughly two-thirds (66.2%) of admissions. Although the annual admission rate has risen, the incidence of pediatric burn admissions, particularly among Hispanic and African American children has declined. The most common causes of admission were scald (42%), flame (29%), and contact burns (10%). Both the median length of hospitalization and burn size have decreased over time (r(2)=0.75 and 0.62, respectively). Mortality was significantly correlated with inhalation injury, size of burn, and history of abuse. It was negatively correlated with year of admission. CONCLUSIONS: Over 35 years in North Texas, the median burn size and incidence of pediatric burn admissions has decreased. Concomitantly, length of stay and mortality have also decreased.

The Parkland Burn Center experience with 297 cases of child abuse from 1974 to 2010.

INTRODUCTION: Pediatric burns due to abuse are unfortunately relatively common, accounting for 5.8-8.8% of all cases of abuse annually. Our goal was to evaluate our 36-year experience in the evaluation and management of the victims of abuse in the North Texas area. METHODS: A prospectively maintained database containing records on all admissions from 1974 through 2010 was queried for all patients aged less than 18 years. Patients admitted for management of a non-burn injury were excluded from the analysis. RESULTS: Of 5,553 pediatric burn admissions, 297 (5.3%) were due to abuse. Children with non-accidental injuries tended to be younger (2.1 vs. 5.0 years, p<0.0001) and male (66.0 vs. 56.5%, p=0.0008). Scald was the most common mechanism of injury overall (44.8%), and was also the predominant cause of inflicted burns (89.6 vs. 42.3%, p<0.0001). Multivariate logistic regression identified age, gender, presence of a scald, contact, or chemical burn, and injury to the hands, bilateral feet, buttocks, back, and perineum to be significant predictors of abuse. Victims of abuse were also found to have worse outcomes, including mortality (5.4 vs. 2.3%, p=0.0005). After adjusting for age, mechanism of injury, and burn size, abuse remained a significant predictor of mortality (OR 3.3, 95% CI 1.5-7.2) CONCLUSIONS: Clinicians should approach all burn injuries in young children with a high index of suspicion, but in particular those with scalds, or injuries to the buttocks, perineum, or bilateral feet should provoke suspicion. Burns due to abuse are associated with worse outcomes, including length of stay and mortality.

Skeletal Muscle Loss is Associated with TNF Mediated Insufficient Skeletal Myogenic Activation After Burn.

Muscle loss accompanies severe burn; in this hyper-catabolic state, muscle undergoes atrophy through protein degradation and disuse. Muscle volume is related to the relative rates of cellular degradation and myogenesis. We hypothesize that muscle atrophy after injury is in part because of insufficient myogenesis associated with the hyper-inflammatory response. The aim of this study was to investigate the role of skeletal myogenesis and muscle cell homeostasis in response to severe burn. Twenty-eight male C57BL6 mice received 25% TBSA scald. Gluteus muscle from these animals was analyzed at days 1, 3, 7, and 14 after injury. Six additional animals without burn served as controls. We showed muscle wet weight and protein content decreased at days 3 and 7 after burn, with elevated tumor necrosis factor (TNF) mRNA expression (P < 0.05). Increased cell death was observed through TUNEL staining, and cleaved caspase-3 levels reached a peak in muscle lysate at day 3 (P < 0.05). The cell proliferation marker proliferating cell nuclear antigen (PCNA) significantly increased after burn, associated with increased gene and protein expression of myogenesis markers Pax7 and myogenin. Desmin mRNA expression and the ratio of desmin to PCNA protein expression, however, significantly decreased at day 7 (P < 0.05). In vitro, the ratio of desmin to PCNA protein expression significantly decreased in C2C12 murine myoblasts after TNF-α stimulation for 24 h. We showed that severe burn induces both increased cell death and proliferation. Myogenesis, however, does not counterbalance increased cell death after burn. Data suggest insufficient myogenesis might be associated with pro-inflammatory mediator TNF activity.

Radiation exposure and safety practices during pediatric central line placement.

PURPOSE: Pediatric surgeons routinely use fluoroscopy for central venous line (CVL) placement. We examined radiation safety practices and patient/surgeon exposure during fluoroscopic CVL. METHODS: Fluoroscopic CVL procedures performed by 11 pediatric surgeons in 2012 were reviewed. Fluoroscopic time (FT), patient exposure (mGy), and procedural data were collected. Anthropomorphic phantom simulations were used to calculate scatter and dose (mSv). Surgeons were surveyed regarding safety practices. RESULTS: 386 procedures were reviewed. Median FT was 12.8 seconds. Median patient estimated effective dose was 0.13 mSv. Median annual FT per surgeon was 15.4 minutes. Simulations showed no significant difference (p=0.14) between reported exposures (median 3.5 mGy/minute) and the modeled regression exposures from the C-arm default mode (median 3.4 mGy/minute). Median calculated surgeon exposure was 1.5 mGy/year. Eight of 11 surgeons responded to the survey. Only three reported 100% lead protection and frequent dosimeter use. CONCLUSION: We found nonstandard radiation training, safety practices, and dose monitoring for the 11 surgeons. Based on simulations, the C-arm default setting was typically used instead of low dose. While most CVL procedures have low patient/surgeon doses, every effort should be used to minimize patient and occupational exposure, suggesting the need for formal hands-on training for nonradiologist providers using fluoroscopy.