Systemic long-term metabolic effects of acute non-severe paediatric burn injury.
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ABSTRACT:
SUBMITTER: Begum S
PROVIDER: S-EPMC9338081 | biostudies-literature | 2022 Jul
REPOSITORIES: biostudies-literature
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Systemic long-term metabolic effects of acute non-severe paediatric burn injury.
Begum Sofina S Johnson Blair Z BZ Morillon Aude-Claire AC Yang Rongchang R Bong Sze How SH Whiley Luke L Gray Nicola N Fear Vanessa S VS Cuttle Leila L Holland Andrew J A AJA Nicholson Jeremy K JK Wood Fiona M FM Fear Mark W MW Holmes Elaine E
Scientific reports 20220729 1
A growing body of evidence supports the concept of a systemic response to non-severe thermal trauma. This provokes an immunosuppressed state that predisposes paediatric patients to poor recovery and increased risk of secondary morbidity. In this study, to understand the long-term systemic effects of non-severe burns in children, targeted mass spectrometry assays for biogenic amines and tryptophan metabolites were performed on plasma collected from child burn patients at least three years post in ...[more]
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Project description:Main contributors to adverse outcomes in severely burned pediatric patients are profound and complex metabolic changes in response to the initial injury. It is currently unknown how long these conditions persist beyond the acute phase post-injury. The aim of the present study was to examine the persistence of abnormalities of various clinical parameters commonly utilized to assess the degree hypermetabolic and inflammatory alterations in severely burned children for up to three years post-burn to identify patient specific therapeutic needs and interventions.Nine-hundred seventy-seven severely burned pediatric patients with burns over 30% of the total body surface admitted to our institution between 1998 and 2008 were enrolled in this study and compared to a cohort non-burned, non-injured children. Demographics and clinical outcomes, hypermetabolism, body composition, organ function, inflammatory and acute phase responses were determined at admission and subsequent regular intervals for up to 36 months post-burn. Statistical analysis was performed using One-way ANOVA, Student's t-test with Bonferroni correction where appropriate with significance accepted at p<0.05. Resting energy expenditure, body composition, metabolic markers, cardiac and organ function clearly demonstrated that burn caused profound alterations for up to three years post-burn demonstrating marked and prolonged hypermetabolism, p<0.05. Along with increased hypermetabolism, significant elevation of cortisol, catecholamines, cytokines, and acute phase proteins indicate that burn patients are in a hyperinflammatory state for up to three years post-burn p<0.05.Severe burn injury leads to a much more profound and prolonged hypermetabolic and hyperinflammatory response than previously shown. Given the tremendous adverse events associated with the hypermetabolic and hyperinflamamtory responses, we now identified treatment needs for severely burned patients for a much more prolonged time.
| S-EPMC3138751 | biostudies-literature
Project description:BackgroundSepsis, trauma, and burn injury acutely depress systolic and diastolic cardiac function; data on long-term cardiac sequelae of pediatric critical illness are sparse. This study evaluated long-term systolic and diastolic function, myocardial fibrosis, and exercise tolerance in survivors of severe pediatric burn injury.MethodsSubjects at least 5 years after severe burn (post-burn:PB) and age-matched healthy controls (HC) underwent echocardiography to quantify systolic function (ejection fraction[EF%]), diastolic function (E/e'), and myocardial fibrosis (calibrated integrated backscatter) of the left ventricle. Exercise tolerance was quantified by oxygen consumption (VO2) and heart rate at rest and peak exercise. Demographic information, clinical data, and biomarker expression were used to predict long-term cardiac dysfunction and fibrosis.FindingsSixty-five subjects (PB:40;HC:25) were evaluated. At study date, PB subjects were 19±5 years, were at 12±4 years postburn, and had burns over 59±19% of total body surface area, sustained at 8±5 years of age. The PB group had lower EF% (PB:52±9%;HC:61±6%; p=0.004), E/e' (PB:9.8±2.9;HC: 5.4±0.9;p<0.0001), VO2peak (PB:37.9±12;HC: 46±8.32 ml/min/kg; p=0.029), and peak heart rate (PB:161±26;HC:182±13bpm;p=0.007). The PB group had moderate (28%) or severe (15%) systolic dysfunction, moderate (50%) or severe diastolic dysfunction (21%), and myocardial fibrosis (18%). Biomarkers and clinical parameters predicted myocardial fibrosis, systolic dysfunction, and diastolic dysfunction.InterpretationSevere pediatric burn injury may have lasting impact on cardiac function into young adulthood and is associated with myocardial fibrosis and reduced exercise tolerance. Given the strong predictive value of systolic and diastolic dysfunction, these patients might be at increased risk for early heart failure, associated morbidity, and mortality.FundingConflicts of Interest and Sources of Funding: The authors do not have any conflicts of interest to declare. This work was supported by NIH (P50 GM060338, R01 GM056687, R01 HD049471, R01 GM112936, R01-GM56687 and T32 GM008256), NIDILRR (H133A120091, 90DP00430100), Shriners Hospitals for Children (84080, 79141, 79135, 71009, 80100, 71008, 87300 and 71000), FAER (MRTG CON14876), and the Department of Defense (W81XWH-14-2-0162 and W81XWH1420162). It was also made possible with the support of UTMB's Institute for Translational Sciences, supported in part by a Clinical and Translational Science Award (UL1TR000071) from the National Center for Advancing Translational Sciences (NIH).
| S-EPMC5865217 | biostudies-literature
Project description:BackgroundRecent evidence suggests that burn patients are at increased risk of hospital admission for infection, mental health conditions, cardiovascular disease and cancer for many years after discharge for the burn injury itself. Burn injury has also been shown to induce sustained immune system dysfunction. This change to immune function may contribute to the increased risk of chronic disease observed. However, the mechanisms that disrupt long-term immune function in response to burn trauma, and their link to long-term morbidity, remain unknown. In this study we investigated changes to immune function after burn injury using a murine model of non-severe injury.MethodsAn established mouse model of non-severe burn injury (full thickness burn equivalent to 8% total body surface area) was used in combination with an orthotopic model of B16 melanoma to investigate the link between burns and cancer. Considering that CD8+ T cells are important drivers of effective tumour suppression in this model, we also investigated potential dysregulation of this immune population using mouse models of burn injury in combination with herpes simplex virus infection. Flow cytometry was used to detect and quantify cell populations of interest and changes in immune function.ResultsWe demonstrate that 4 weeks after a non-severe burn injury, mice were significantly more susceptible to tumour development than controls using an orthotopic model of B16 melanoma. In addition, our results reveal that CD8+ T cell expansion, differentiation and memory potential is significantly impaired at 1 month post-burn.ConclusionsOur data suggests that CD8+ T cell-mediated immunity may be dysfunctional for a sustained period after even non-severe burn injury. Further studies in patients to validate these findings may support clinical intervention to restore or protect immunity in patients after burn injury and reduce the increased risk of secondary morbidities observed.
| S-EPMC9054911 | biostudies-literature
Project description:BackgroundPatients who have survive a burn injury might be at risk of opioid dependence after discharge. This study examined the use of opioids in patients who suffer burn injury and explored factors associated with persistent opioid use after hospital discharge.MethodsThis retrospective cohort study compared adults admitted with a burn injury from 2009 to 2019 with two matched comparison cohorts from the general population and adults with a diagnosis of acute pancreatitis. Pre-admission prescription opioid use was determined, and a multivariable negative binomial regression analysis used to explore post-discharge opioid use.ResultsA total of 7147 burn patients were matched with 6810 pancreatitis patients and with 28 184 individuals from the general population. Pre-admission opioid use was higher in the burn and pancreatitis cohorts (29% and 40%, respectively) compared with the general population (17%). Opioid use increased in both burn and pancreatitis cohorts after discharge (41% and 53%, respectively), although patients with pancreatitis were at even higher risk of increased opioid use in an adjusted analysis (incidence rate ratio 1.43). Female sex, lower socioeconomic status, ICU admission, pre-injury opioid use, and a history of excess alcohol use were all associated with an increase in opioid prescriptions after discharge.ConclusionsOpioid use is high in those admitted with a burn injury or acute pancreatitis when compared with the general population, increasing further after hospital discharge. Female sex and socioeconomic deprivation are among factors that make increased opioid use more likely, although this phenomenon seems even more pronounced in those with acute pancreatitis compared with burn injuries.
| S-EPMC10870133 | biostudies-literature
Project description:BackgroundThe extent of the consequences of an episode of severe acute kidney injury (AKI) on long-term outcome of critically ill patients remain debated. We conducted a prospective follow-up of patients included in a large multicenter clinical trial of renal replacement therapy (RRT) initiation strategy during severe AKI (the Artificial Kidney Initiation in Kidney Injury, AKIKI) to investigate long-term survival, renal outcome and health related quality of life (HRQOL). We also assessed the influence of RRT initiation strategy on these outcomes.ResultsFollow-up of patients extended from 60 days to a median of 3.35 years [interquartile range (IQR), 1.89 to 4.09] after the end of initial study. Of the 619 patients included in the AKIKI trial, 316 survived after 60 days. The overall survival rate at 3 years from inclusion was 39.4% (95% CI 35.4 to 43.4). A total of 46 patients (on the 175 with available data on long-term kidney function) experienced worsening of renal function (WRF) at the time of follow-up [overall incidence of 26%, cumulative incidence at 4 years: 20.6% (CI 95% 13.0 to 28.3)]. Fifteen patients required chronic dialysis (5% of patients who survived after day 90). Among the 226 long-term survivors, 80 (35%) answered the EQ-5D questionnaire. The median index value reported was 0.67 (IQR 0.40 to 1.00) indicating a noticeable alteration of quality of life. Initiation strategy for RRT had no effect on any long-term outcome.ConclusionSevere AKI in critically ill patients was associated with a high proportion of death within the first 2 months but less so during long-term follow-up. A quarter of long-term survivors experienced a WRF and suffered from a noticeable impairment of quality of life. Renal replacement therapy initiation strategy was not associated with mortality outcome.
| S-EPMC10008759 | biostudies-literature
Project description:Severe sepsis, a systemic inflammatory response to infection, is an increasing cause of morbidity in intensive care units. During sepsis, the vasculature is profoundly altered, leading to release of microbial virulence factors and proinflammatory mediators to surrounding tissue, causing severe systemic inflammatory responses and hypoxic injury of multiple organs. To date, multiple studies have explored pathologic conditions in many vital organs, including lungs, liver, and kidneys. Although data suggest that sepsis is emerging as a key driver of chronic brain dysfunction, the immunological consequence of severe inflammatory responses in the brain remain poorly understood. In this study, we used C57BL/6 sepsis mouse models to establish a disease phenotype in which septic mice with various degrees of severity recover. In the early phases of sepsis, monocytes infiltrate the brain with significantly elevated proinflammatory cytokine levels. In recovered animals, monocytes return to vehicle levels, but the number of brain-resident microglia is significantly increased in the cortex, the majority of which remain activated. The increase in microglia number is mainly due to self-proliferation, which is completely abolished in CCR2 knockout mice. Collectively our data suggest that early monocyte infiltration causes permanent changes to microglia during sepsis, which may ultimately dictate the outcome of future infections and neuropathological diseases.
| S-EPMC6868345 | biostudies-literature
Project description:The inflammatory response initiated upon burn injury is also associated with extensive metabolic adjustments. While there is a significant body of literature on the characterization of these changes at the metabolite level, little is known on the mechanisms of induction, especially with respect to the role of gene expression. We have comprehensively analyzed changes in gene expression in rat livers during the first 7 d after 20% total body surface area burn injury using Affymetrix microarrays. A total of 740 genes were significantly altered in expression at 1, 2, 4, and 7 d after burn injury compared to sham-burn controls. Functional classification based on gene ontology terms indicated that metabolism, transport, signaling, and defense/inflammation response accounted for more than 70% of the significantly altered genes. Fisher least-significant difference post-hoc testing of the 740 differentially expressed genes indicated that over 60% of the genes demonstrated significant changes in expression either on d 1 or on d 7 postburn. The gene expression trends were corroborated by biochemical measurements of triglycerides and fatty acids 24 h postburn but not at later time points. This suggests that fatty acids are used, at least in part, in the liver as energy substrates for the first 4 d after injury. Our data also suggest that long-term regulation of energy substrate utilization in the liver following burn injury is primarily at the posttranscriptional level. Last, relevance networks of significantly expressed genes indicate the involvement of key small molecules in the hepatic response to 20% total body surface area burn injury.
| S-EPMC3235793 | biostudies-literature
Project description:BackgroundBurns are associated with hyperglycemia leading to increased incidence of infections with pneumonia being one of the most prominent and adverse complications. Recently, various studies in critically ill patients indicated that increased pulmonary glucose levels with airway/blood glucose threshold over 150 mg/dl lead to an overwhelming growth of bacteria in the broncho-pulmonary system, subsequently resulting in an increased risk of pulmonary infections. The aim of the present study was to determine whether a similar cutoff value exists for severely burned pediatric patients.MethodsOne-hundred six severely burned pediatric patients were enrolled in the study. Patients were divided in two groups: high (H) defined as daily average glucose levels >75% of LOS >150 mg/dl), and low (L) with daily average glucose levels >75% of the LOS <150 mg/dl). Incidences of pneumonia, atelectasis, and acute respiratory distress syndrome (ARDS) were assessed. Incidence of infections, sepsis, and respiratory parameters were recorded. Blood was analyzed for glucose and insulin levels. Statistical analysis was performed using Student's t-test and chi-square test. Significance was set at p<0.05.ResultsPatient groups were similar in demographics and injury characteristics. Pneumonia in patients on the mechanical ventilation (L: 21%, H: 32%) and off mechanical ventilation (L: 5%, H: 15%), as well as ARDS were significantly higher in the high group (L: 3%, H: 19%), p<0.05, while atelectasis was not different. Patients in the high group required significantly longer ventilation compared to low patients (p<0.05). Furthermore, incidence of infection and sepsis were significantly higher in the high group, p<0.05.ConclusionOur results indicate that systemic glucose levels over 150 mg/dl are associated with a higher incidence of pneumonia confirming the previous studies in critically ill patients.
| S-EPMC3959591 | biostudies-literature
Project description:BackgroundAcute kidney injury (AKI) is a morbid complication and the main cause of multiple organ failure and death in severely burned patients. The objective of this study was to explore epidemiology, risk factors, and outcomes of AKI for severely burned patients.MethodsThis retrospective study was performed with prospectively collected data of severely burned patients from the Institute of Burn Research in Southwest Hospital during 2011-2017. AKI was diagnosed according to Kidney Disease Improving Global Outcomes (KDIGO) criteria (2012), and it was divided into early and late AKIs depending on its onset time (within the first 3 days or >3 days post burn). The baseline characteristics, clinical data, and outcomes of the three groups (early AKI, late AKI and non-AKI) were compared using logistic regression analysis. Mortality predictors of patients with AKI were assessed.ResultsA total of 637 adult patients were included in analysis. The incidence of AKI was 36.9% (early AKI 29.4%, late AKI 10.0%). Multiple logistic regression analysis revealed that age, gender, total burn surface area (TBSA), full-thickness burns of TBSA, chronic comorbidities (hypertension or/and diabetes), hypovolemic shock of early burn, and tracheotomy were independent risk factors for both early and late AKIs. However, sepsis was only an independent risk factor for late AKI. Decompression escharotomy was a protective factor for both AKIs. The mortality of patients with AKI was 32.3% (early AKI 25.7%, late AKI 56.3%), and that of patients without AKI was 2.5%. AKI was independently associated with obviously increased mortality of severely burned patients [early AKI, OR = 12.98 (6.08-27.72); late AKI, OR = 34.02 (15.69-73.75)]. Compared with patients with early AKI, patients with late AKI had higher 28-day mortality (34.9% vs. 19.4%, p = 0.007), 90-day mortality (57.1% vs. 27.4%, p < 0.0001).ConclusionsAKI remains prevalent and is associated with high mortality in severely burned patients. Late-onset acute kidney injury had greater severity and worse prognosis.
| S-EPMC9108380 | biostudies-literature
Project description:BackgroundAcute kidney injury (AKI) is a risk factor for neurocognitive impairment in severe malaria (SM), but the impact of AKI on long-term behavioral outcomes following SM is unknown.MethodsWe conducted a prospective study on behavioral outcomes of Ugandan children 1.5 to 12 years of age with two forms of severe malaria, cerebral malaria (CM, n = 226) or severe malarial anemia (SMA, n = 214), and healthy community children (CC, n = 173). AKI was defined as a 50% increase in creatinine from estimated baseline. Behavior and executive function were assessed at baseline and 6, 12, and 24 months later using the Child Behavior Checklist and Behavior Rating Inventory of Executive Function, respectively. Age-adjusted z-scores were computed for each domain based on CC scores. The association between AKI and behavioral outcomes was evaluated across all time points using linear mixed effect models, adjusting for sociodemographic variables and disease severity.ResultsAKI was present in 33.2% of children with CM or SMA at baseline. Children ≥6 years of age with CM or SMA who had AKI on admission had worse scores in socio-emotional function in externalizing behaviors (Beta (95% CI), 0.52 (0.20, 0.85), p = 0.001), global executive function (0.48 (0.15, 0.82), p = 0.005) and behavioral regulation (0.66 (0.32, 1.01), p = 0.0002) than children without AKI. There were no behavioral differences associated with AKI in children <6 years of age.ConclusionsAKI is associated with long-term behavioral problems in children ≥6 years of age with CM or SMA, irrespective of age at study enrollment.
| S-EPMC6917349 | biostudies-literature