Burn-injured skin is marked by a prolonged local acute inflammatory response of innate immune cells and pro-inflammatory cytokines.

The systemic and local immune response in burn patients is often extreme and derailed. As excessive inflammation can damage healthy tissues and slow down the healing process, modulation of inflammatory responses could limit complications and improve recovery. Due to its complexity, more detailed information on the immune effects of thermal injury is needed to improve patient outcomes. We therefore characterized and quantified subsets of immune cells and mediators present in human burn wound tissue (eschar), sampled at various time points. This study shows that after burn injury, the number of immune cells were persistently increased, unlike the normal wound healing process. There was an immediate, strong increase in neutrophils and a moderate increase in monocytes/macrophages and lymphocytes, especially in the second and third week post burn. The percentage of classical (CD14highCD16-) monocytes/macrophages demonstrated a steady decrease over time, whereas the proportion of intermediate (CD14highCD16+) monocytes/macrophages slowly increased. The absolute numbers of T cells, NK cells and B cells increased up to week 3, while the fraction of γδ T cells was increased only in week 1. Secretome profiling revealed high levels of chemokines and an overall pro-inflammatory cytokine milieu in burn tissue. The local burn immune response shows similarities to the systemic immune reaction, but differs in neutrophil maturity and lymphocyte composition. Altogether, the neutrophil surges, high levels of pro-inflammatory cytokines and limited immunosuppression might be key factors that prolong the inflammation phase and delay the wound healing process in burns.

Predictability of exercise capacity following pediatric burns: a preliminary investigation.

PURPOSE: Describe the course of exercise capacity in pediatric burn patients during the initial 6 months after hospital discharge, and examine whether its recovery can be predicted from burn characteristics, sociodemographic characteristics, and/or prior assessment. MATERIALS AND METHODS: Exercise capacity was assessed at discharge, and 6 weeks, 3 months, and 6 months after discharge using the Steep Ramp Test (SRT). RESULTS: Twenty-four pediatric patients with burns affecting 0.1-34% of total body surface area were included. At group level, exercise capacity was low at discharge and did not reach healthy reference values within 6 months, despite significant improvement over time. At individual level, the course of exercise capacity varied widely. Six months after discharge, 48% of participants scored more than one standard deviation below healthy age- and sex-specific reference values. SRT outcomes at 6 weeks and 3 months were the best predictors of exercise capacity 6 months after discharge, explaining, respectively, 76% and 93% of variance. CONCLUSIONS: Forty-eight percent of participants did not achieve healthy reference values of exercise capacity and were therefore considered "at risk" for diminished functioning. Our preliminary conclusion that early assessment of exercise capacity with the SRT can timely identify those patients, needs to be strengthened by further research.IMPLICATIONS FOR REHABILITATIONPediatric burns can be considered as a chronic medical condition because of the lifelong consequences.Exercise capacity is reduced following- even minor -pediatric burns.Recovery patterns vary widely: some pediatric burn patients achieve healthy levels of exercise capacity without specific intervention, while others do not.The Steep Ramp Test can be used to assess exercise capacity, identifying those "at risk" for adverse outcomes at an early stage.Patients "at risk" should be encouraged to play sports and adopt an active lifestyle.

Persistent Systemic Inflammation in Patients With Severe Burn Injury Is Accompanied by Influx of Immature Neutrophils and Shifts in T Cell Subsets and Cytokine Profiles.

Severe burn injury causes local and systemic immune responses that can persist up to months, and can lead to systemic inflammatory response syndrome, organ damage and long-term sequalae such as hypertrophic scarring. To prevent these pathological conditions, a better understanding of the underlying mechanisms is essential. In this longitudinal study, we analyzed the temporal peripheral blood immune profile of 20 burn wound patients admitted to the intensive care by flow cytometry and secretome profiling, and compared this to data from 20 healthy subjects. The patient cohort showed signs of systemic inflammation and persistently high levels of pro-inflammatory soluble mediators, such as IL-6, IL-8, MCP-1, MIP-1ß, and MIP-3α, were measured. Using both unsupervised and supervised flow cytometry techniques, we observed a continuous release of neutrophils and monocytes into the blood for at least 39 days. Increased numbers of immature neutrophils were present in peripheral blood in the first three weeks after injury (0.1-2.8 × 106/ml after burn vs. 5 × 103/ml in healthy controls). Total lymphocyte numbers did not increase, but numbers of effector T cells as well as regulatory T cells were increased from the second week onward. Within the CD4+ T cell population, elevated numbers of CCR4+CCR6- and CCR4+CCR6+ cells were found. Altogether, these data reveal that severe burn injury induced a persistent innate inflammatory response, including a release of immature neutrophils, and shifts in the T cell composition toward an overall more pro-inflammatory phenotype, thereby continuing systemic inflammation and increasing the risk of secondary complications.

Course of prevalence of scar contractures limiting function: A preliminary study in children and adolescents after burns.

BACKGROUND: Scar contracture is a well-known sequela of burns that is specifically relevant as it may limit function. Reports regarding the course of scar contractures, however, are scarce and, moreover, not focussed on function. This study describes the course of prevalence of scar contractures that limit function in children and adolescents after burns. METHOD: Range of motion (ROM) of extremity joints of 20 children and adolescents after burns were assessed at discharge (T0) and at six weeks (T1), three months (T2), and six months (T3) after discharge. A scar contracture limiting function was defined as a measured ROM lower than the functional ROM, i.e., ROM used to perform daily activities by unimpaired subjects. RESULTS: At discharge (T0), 89.5% of the subjects had one or more scar contractures that limited function. Six months later (T3), this prevalence was 76.5%. At discharge (T0), less function limiting scar contractures were found for the upper extremity (29.7%) than the lower extremity (53.3%). Over time, prevalence of contractures in both extremities fluctuated between 22% and 35%. CONCLUSIONS: The majority of children and adolescents (13/17) still had scar contractures limiting function six months after discharge (T3). Substantial longitudinal studies over a longer period of time are needed to increase our knowledge on the course of these scar contractures in order to support improvements in burn care. TRIAL REGISTRATION: The study is approved by the Regional Committee for Patient-Oriented Research Leeuwarden in the Netherlands (NL45917.099.13).