Skeletal muscle wasting after burn is regulated by a decrease in anabolic signaling in the early flow phase.

Following burns a sustained catabolic stress response is activated, resulting in skeletal muscle wasting. A better understanding of the underlying mechanisms of postburn skeletal muscle wasting is essential for the development of preventive and/or therapeutic strategies. Six weeks old female rats underwent a sham, 10% or 40% total body surface area scald burn. Ten days post-injury, severely burned animals gained significantly less weight compared to sham treated and minor burned animals, reflected in a significantly lower ratio of muscle to total body weight for Soleus (SOL) and Extensor Digitorum Longus (EDL) in the severely burned group. Postburn, total fiber number was significantly lower in EDL, while in SOL the amount of type1 fibers significantly increased and type2 fibers significantly decreased. No signs of mitochondrial dysfunction (COX/SDH) or apoptosis (caspase-3) were found. In SOL and EDL, eEF2 and pAKT expression was significantly lower after severe burn. MURF1,2,3 and Atrogin-1 was significantly higher in SOL, whilst in EDL MURF1,2,3 was significantly lower postburn. In both muscles, FOXO3A was significantly lower postburn. This study identified postburn changes in muscle anthropomorphology and proteins involved in pathways regulating protein synthesis and breakdown, with more pronounced catabolic effects in SOL.

Effects of exercise training on muscle wasting, muscle strength and quality of life in adults with acute burn injury.

OBJECTIVES: Exercise training during the acute phase of burns is difficult to implement but offers potential benefits. This multicenter trial explored the effects of an exercise program on muscular changes and quality of life during burn center stay. METHODS: Fifty-seven adults with burns ranging between 10% and 70% TBSA were allocated to receive either standard of care (n = 29), or additionally exercise (n = 28), consisting of resistance and aerobic training, commenced as early as possible according to safety criteria. Muscle wasting (primary outcome), quantified by ultrasound-derived quadriceps muscle layer thickness (QMLT) and rectus femoris cross-sectional area (RF-CSA), muscle strength and quality of life (Burn Specific Health Scale-Brief (BSHS-B) and EQ-5D-5L) were assessed at baseline, four and eight weeks later, or hospital discharge. Mixed models were used to analyze between-group changes over time with covariates of interest added in stepwise forward modeling. RESULTS: The addition of exercise training to standard of care induced significant improvements in QMLT, RF-CSA, muscle strength and the BSHS-B subscale hand function (ß-coefficient. 0.055 cm/week of QMLT, p = 0.005). No added benefit was observed for other quality-of-life measures. CONCLUSIONS: Exercise training, administered during the acute phase of burns, reduced muscle wasting, and improved muscle strength throughout burn center stay.

Molecular mechanisms of post-burn muscle wasting and the therapeutic potential of physical exercise.

After a severe burn injury, a systemic stress response activates metabolic and inflammatory derangements that, among other, leads to muscle mass loss (muscle wasting). These negative effects on skeletal muscle continue for several months or years and are aggravated by short-term and long-term disuse. The dynamic balance between muscle protein synthesis and muscle protein breakdown (proteolysis) is regulated by complex signalling pathways that leads to an overall negative protein balance in skeletal muscle after a burn injury. Research concerning these molecular mechanisms is still scarce and inconclusive, understanding of which, if any, molecular mechanisms contribute to muscle wasting is of fundamental importance in designing of therapeutic interventions for burn patients as well. This review not only summarizes our present knowledge of the molecular mechanisms that underpin muscle protein balance but also summarizes the effects of exercise on muscle wasting post-burn as promising strategy to counteract the detrimental effects on skeletal muscle. Future research focusing on the pathways causing post-burn muscle wasting and the different effects of exercise on them is needed to confirm this hypothesis and to lay the foundation of therapeutic strategies.

Reliability and feasibility of skeletal muscle ultrasound in the acute burn setting.

OBJECTIVES: Despite the impact of muscle wasting after burn, tools to quantify muscle wasting are lacking. This multi-centre study examined the utility of ultrasound to measure muscle mass in acute burn patients comparing different methodologies. METHODS: B-mode ultrasound was used by two raters to determine feasibility and inter-rater reliability in twenty burned adults following admission. Quadriceps muscle layer thickness (QMLT) and rectus femoris cross-sectional area (RF-CSA) were measured, comparing the use of i) a single versus average measurements, ii) a proximal versus distal location for QMLT, and iii) a maximum- versus no-compression technique for QMLT. RESULTS: Analysis of twenty burned adults (50 years [95%CI 42-57], 32%TBSA [95%CI 23-40]) yielded ICCs of> 0.97 for QMLT (for either location and compression technique) and> 0.95 for RF-CSA, using average measurements. Relative minimal detectable changes were smaller using no-compression than maximum-compression (6.5% vs. 15%). Using no-compression to measure QMLT was deemed feasible for both proximal and distal locations (94% and 96% of attempted measurements). In 9.5% of cases maximum-compression was not feasible. 95% of RF-CSA measurements were successfully completed. CONCLUSION: Ultrasound provides feasible and reliable values of quadriceps muscle architecture that can be adapted to clinical scenarios commonly encountered in acute burn settings.

Breast edema, from diagnosis to treatment: state of the art.

INTRODUCTION: Breast edema can arise from different etiologies; however, it is mostly seen after breast conserving surgery and/or radiotherapy. Combining breast conserving surgery and radiotherapy can cause damage to the lymphatic system and reactions to surrounding tissues, which can lead to breast edema; hereby, the breast size can increase by more than one cup size. Swelling of the breast is not the only criterion associated with breast edema. Other common criteria found in literature are peau d'orange, heaviness of the breast, skin thickening, breast pain, redness of the skin, hyperpigmented skin pores and a positive pitting sign. Despite the benefits of breast conserving surgery, breast edema can be uncomfortable, and can negatively influence quality of life in suffering patients. In contrast to lymphedema of the arm, which is well known in clinical practice and in research, breast edema is often underestimated and far less explored in literature. Currently, many aspects still need to be reviewed. PURPOSE AND IMPORTANCE TO PRACTICE: This masterclass aims at providing the state of the art of breast edema for all health care workers and researchers involved in the treatment and monitoring of breast cancer patients. It includes current and future perspectives on its diagnosis, longitudinal course and treatment. Furthermore, recommendations for clinical practice and future research are discussed. CLINICAL IMPLICATIONS: It is recommended to closely monitor those patients in whom breast edema symptoms do not decline within 6 months after termination of radiotherapy and provide them with the appropriate therapy. Since evidence concerning the treatment of breast edema is currently lacking, we recommend the complex decongestive therapy (CDT) to the utmost extent, by analogy with the lymphedema treatment of the extremities. This treatment involves skin care, exercise therapy and compression. Additionally, all patients should be informed about the normal course of breast edema development. FUTURE RESEARCH PRIORITIES: A consensus should be reached among clinicians and researchers concerning the definition, assessment methods and best treatment of breast edema. Furthermore, high quality studies are necessary to prove the effectiveness of the CDT for breast edema.