Update on Hypermetabolism in Pediatric Burn Patients.

Despite advancements in pediatric burn care, the profound hypermetabolic response associated with severe burns remains a multifaceted challenge throughout the continuum of care. Understanding the various physiologic disturbances that constitute hypermetabolism is crucial for a thorough evaluation and for implementing appropriate surgical and nonsurgical interventions. In this article, we describe the pathophysiology and treatment of hypermetabolism in pediatric burn patients with a focus on reducing resting energy requirements, minimizing infection, and optimizing nutrition for patients undergoing frequent surgical intervention.

Focal incidental colorectal fluorodeoxyglucose uptake: Should it be spotlighted?

Fluorine-18 fluorodeoxyglucose (F-18 FDG) positron emission tomography/computed tomography (PET/CT) has emerged as a cornerstone in cancer evaluation imaging, with a well-established history spanning several years. This imaging modality, encompassing the examination of the body from the base of the skull to the upper thighs, comprehensively covers the chest and abdominopelvic regions in a singular scan, allowing for a holistic assessment of nearly the entire body, including areas of marginal interest. The inherent advantage of this expansive scan range lies in its potential to unveil unexpected incidental abnormal hypermetabolic areas. The identification of incidental focal FDG uptake within colorectal regions during PET/CT scans is not an uncommon occurrence, albeit fraught with challenges associated with non-specific FDG uptake. The presence of benign colorectal lesions or physiological uptake poses a particular obstacle, as these may manifest with FDG uptake levels that mimic malignancy. Consequently, physicians are confronted with a diagnostic dilemma when encountering abnormal FDG uptake in unexpected colorectal areas. Existing studies have presented divergent results concerning these uptakes. Standardized uptake value and its derivatives have served as pivotal metrics in quantifying FDG uptake in PET images. In this article, we aim to succinctly explore the distinctive characteristics of FDG, delve into imaging findings, and elucidate the clinical significance of incidental focal colorectal uptake. This discussion aims to contribute valuable insights into the nuanced interpretation of such findings, fostering a comprehensive understanding.

Energy expenditure during nutritional rehabilitation: a scoping review to investigate hypermetabolism in individuals with anorexia nervosa.

BACKGROUND: Weight gain and nutritional rehabilitation are essential first steps to achieve medical stabilization in anorexia nervosa, and frequent resistance to weight gain requires patients to consume high kilocalorie loads. Adaptive hypometabolism is common when patients begin treatment, and rebound hypermetabolism is suspected to be a significant barrier to weight gain. The aim of this review was to summarize existing data describing metabolic changes in anorexia nervosa during weight restoration. The reported findings challenge current hypotheses of weight gain resistance and highlight key areas for future research. METHODS: Using scoping review guidelines, three databases were searched for studies investigating metabolic changes in anorexia nervosa before and after renourishment. Two reviewers systematically screened the titles and abstracts of 447 articles, and full-text versions of 106 studies were assessed for eligibility. A total of 36 studies were included for review. Data regarding the study description, sample population (including age, weight, BMI, duration of treatment, and caloric intake), and metabolic variable descriptions were extracted. RESULTS: Female patients with anorexia nervosa from studies across 13 countries were included. Across the studies, average BMI increased from 13.7 kg/m2 at admission to 17.57 kg/m2. Patients presented to treatment with clinically reduced energy expenditure levels. After varying levels of nutritional rehabilitation and weight restoration, measured energy expenditure increased significantly in 76% of the studies. Energy expenditure values at the second timepoint increased to the standard range for normal weight female teenagers and adults. Despite these increases, the studies do not indicate the presence of a hypermetabolic state during renourishment. Additionally, all studies including both measured and predicted energy expenditure reported that predicted energy expenditure overestimated measured values. CONCLUSION: This study provides a detailed evaluation of the literature investigating energy expenditure and metabolic rate in patients with anorexia nervosa before and following a period of renourishment. The findings from this review identify important gaps in the current beliefs of energy expenditure in anorexia nervosa and highlight a need for further exploration of metabolic alterations during weight restoration.

Nutritional rehabilitation and weight restoration are two primary goals of anorexia nervosa treatment that pose significant physiological and psychological challenges for patients. Patients often require high caloric loads to continue an adequate weight gain trajectory, but the underlying cause of weight gain resistance remains unknown. We completed a scoping review of research into energy expenditure and metabolic rate during treatment. Our search identified 447 relevant articles from academic databases, and 106 were deemed eligible after screening. We extracted data, including sample characteristics, kilocalorie intake, energy expenditure, and treatment information, from 36 studies. When individuals arrived for treatment, their energy expenditure was lower than that of individuals without an eating disorder due to the prolonged state of nutrient deprivation. After varying amounts of time and kilocalorie intake, most studies reported significant increases in energy expenditure. However, energy expenditure after a period of renourishment did not indicate an overactive metabolism (i.e., "hypermetabolism"). Funders should consider supporting exploration of additional factors that may be functioning as barriers to weight gain during treatment, in pursuit of making treatment more efficient and long-lasting. Additionally, future research describing metabolism in anorexia nervosa should provide more consistent methodologies, robust statical testing, and comprehensive reporting of dietary intake.

Increased Pituitary Fluorine-18-Fluorodeoxyglucose Uptake in Patients with Differentiated Thyroid Cancer in Hypothyroidism versus under Recombinant Human Thyroid-Stimulating Hormone Stimulation.

BACKGROUND: 18F-FDG PET/CT is performed for the assessment of radioactive iodine non-avid disease in patients with DTC. In patients prepared by THW, increased pituitary uptake of 18F-FDG in the absence of pituitary disease may reflect the physiological activation of pituitary thyrotroph cells by hypothyroidism. This study aimed to compare pituitary 18F-FDG uptake in patients with DTC under THW vs. rhTSH stimulation. METHODS: A total of 57 patients with DTC undergoing 18F-FDG PET/CT (40 under THW and 17 under rhTSH stimulation) were retrospectively analyzed. Pituitary metabolism was expressed as maximum standardized uptake value (SUVmax) and as SUVratio using the right cerebellum as reference. RESULTS: Pituitary hypermetabolism (SUVmax ≥ 4.1) was present in more patients in the THW group compared to the rhTSH group (62.5% vs. 23.5%; p = 0.01). Pituitary metabolism was significantly higher in the THW group compared to the rhTSH group, as assessed by either SUVmax (mean ± SD: 4.61 ± 1.22, 95%CI: 4.22-5.00 vs. 3.34 ± 0.86, 95%CI: 2.9-3.8; p < 0.001) or SUVratio (0.52 ± 0.11, 95%CI: 0.49-0.56 vs. 0.42 ± 0.07, 95%CI: 0.38-0.46; p < 0.001). Serum TSH levels correlated positively with SUVmax (r = 0.41, p < 0.01) and SUVratio (r = 0.44, p < 0.01) in the THW group only. CONCLUSIONS: The present findings support the hypothesis that pituitary hypermetabolism on 18F-FDG PET/CT in patients with DTC undergoing THW is a common physiological response to hypothyroidism. Awareness of this physiological hypermetabolism is important to avoid potential pitfalls in image interpretation.

Brain 18 F-FDG PET reveals cortico-subcortical hypermetabolic dysfunction in juvenile neuropsychiatric systemic lupus erythematosus.

BACKGROUND: In juvenile systemic lupus erythematosus (j-SLE) with neuropsychiatric (NP) symptoms, there is a lack of diagnostic biomarkers. Thus, we study whether PET-FDG may identify any metabolic dysfunction in j-NPSLE. METHODS: A total of 19 18FDG-PET exams were consecutively performed using PET-MRI system in 11 non-sedated patients presenting with j-NPSLE (11-18y) for less than 18 months (m) and without any significant lesion at MRI. Psychiatric symptoms were scored from 0 (none) to 3 (severe) at PET time. PET images were visually analyzed and voxel-based analyses of cerebral glucose metabolism were performed using statistical parametric mapping (spm) with an age-matched control group, at threshold set > 50 voxels using both p < 0.001 uncorrected (unc.) and p < 0.05 corrected family wise error (FWE). RESULTS: Patients exhibited mainly psychiatric symptoms, with diffuse inflammatory j-NPSLE. First PET (n = 11) was performed at a mean of 15y of age, second/third PET (n = 7/n = 1) 6 to 19 m later. PET individual analysis detected focal bilateral anomalies in 13/19 exams visually but 19/19 using spm (unc.), mostly hypermetabolic areas (18/19). A total of 15% of hypermetabolic areas identified by spm had been missed visually. PET group analysis (n = 19) did not identify any hypometabolic area, but a large bilateral cortico-subcortical hypermetabolic pattern including, by statistical decreasing order (unc.), thalamus, subthalamic brainstem, cerebellum (vermis and cortex), basal ganglia, visual, temporal and frontal cortices. Mostly the subcortical hypermetabolism survived to FWE analysis, being most intense and extensive (51% of total volume) in thalamus and subthalamus brainstem. Hypermetabolism was strictly subcortical in the most severe NP subgroup (n = 8, scores 2-3) whereas it also extended to cerebral cortex, mostly visual, in the less severe subgroup (n = 11, scores 0-1), but difference was not significant. Longitudinal visual analysis was inconclusive due to clinical heterogeneity. CONCLUSIONS: j-NPSLE patients showed a robust bilateral cortico-subcortical hypermetabolic network, focused subcortically, particularly in thalamus, proportionally to psychiatric features severity. Further studies with larger, but homogeneous, cohorts are needed to determine the sensitivity and specificity of this dysfunctional pattern as a potential biomarker in diffuse inflammatory j-NPSLE with normal brain MRI.

Administration and effects of beta blockers and oxandrolone in severely burned adults: a post hoc analysis of the RE-ENERGIZE trial.

Background: Prospective randomized trials in severely burned children have shown the positive effects of oxandrolone (OX), beta blockers (BB) and a combination of the two (BBOX) on hypermetabolism, catabolism and hyperinflammation short- and long-term post-burn. Although data on severely burned adults are lacking in comparison, BB, OX and BBOX appear to be commonly employed in this patient population. In this study, we perform a secondary analysis of an international prospective randomized trial dataset to provide descriptive evidence regarding the current utilization patterns and potential treatment effects of OX, BB and BBOX. Methods: The RE-ENERGIZE (RandomizEd Trial of ENtERal Glutamine to minimIZE Thermal Injury, NCT00985205) trial included 1200 adult patients with severe burns. We stratified patients according to their receipt of OX, BB, BBOX or none of these drugs (None) during acute hospitalization. Descriptive statistics describe the details of drug therapy and unadjusted analyses identify predisposing factors for drug use per group. Association between OX, BB and BBOX and clinical outcomes such as time to discharge alive and 6-month mortality were modeled using adjusted multivariable Cox regressions. Results: More than half of all patients in the trial received either OX (n = 138), BB (n = 293) or BBOX (n = 282), as opposed to None (n = 487, 40.6%). Per study site and geographical region, use of OX, BB and BBOX was highly variable. Predisposing factors for the use of OX, BB and BBOX included larger total body surface area (TBSA) burned, higher acute physiology and chronic health evaluation (APACHE) II scores on admission and younger patient age. After adjustment for multiple covariates, the use of OX was associated with a longer time to discharge alive [hazard ratio (HR) 0.62, confidence interval (CI) (0.47-0.82) per 100% increase, p = 0.001]. A higher proportion of days on BB was associated with lower in-hospital-mortality (HR: 0.5, CI 0.28-0.87, p = 0.015) and 6-month mortality (HR: 0.44, CI 0.24-0.82, p = 0.01). Conclusions: The use of OX, BB and BBOX is common within the adult burn patient population, with its use varying considerably across sites worldwide. Our findings found mixed associations between outcomes and the use of BB and OX in adult burn patients, with lower acute and 6-month-mortality with BB and longer times to discharge with OX. Further research into these pharmacological modulators of the pathophysiological response to severe burn injury is indicated.

Unexpected focal fluorodeoxyglucose uptake in main organs; pass through or pass by?

Since the inception of fluorine-18 fluorodeoxyglucose (F-18 FDG), positron emission tomography/computed tomography (PET/CT) utilizing F-18 FDG has become widely accepted as a valuable imaging modality in the field of oncology, with global prevalence in clinical practice. Given that a single Torso PET/CT scan encompasses the anatomical region from the skull base to the upper thigh, the detection of incidental abnormal focal hypermetabolism in areas of limited clinical interest is both feasible and not uncommon. Numerous investigations have been undertaken to delineate the distinctive features of these findings, yet the outcomes have proven inconclusive. The incongruent results of these studies present a challenge for physicians, leaving them uncertain about the appropriate course of action. This article provides a succinct overview of the characteristics of fluorodeoxyglucose, followed by a comprehensive discussion of the imaging findings and clinical significance associated with incidental focal abnormal F-18 FDG activity in several representative organs. In conclusion, while the prevalence of unrecognized malignancy varies across organs, malignancies account for a substantial proportion, ranging from approximately one-third to over half, of incidental focal uptake. In light of these rates, physicians are urged to exercise vigilance in not disregarding unexpected uptake, facilitating more assured clinical decisions, and advocating for further active evaluation.

Screening and Phasewise Management of Burn Injuries.

Thermal, electrical, chemical, or electromagnetic radiation can cause painful wounds or burns. Spilling hot liquids onto the skin can also cause these kinds of injuries. The two biggest factors contributing to burn injuries in the elderly are smoking and exposure to open flames, while scalding is the primary cause of burn damage in children. Newborns and the elderly make up the majority of burn casualties. In India, there are estimated to be 6-7 million burn cases per year. The high incidence is attributed to the population's illiteracy, poverty, and lack of awareness of safety. The problem is made much worse by the fact that basic and secondary healthcare levels do not provide systematic burn care. Coagulation necrosis is caused by denaturing proteins due to heat from burns. Platelets clump together, arteries narrow, and partly perfused tissue (called the stasis zone) may spread out around the wound. In the stasis zone, tissue is hyperemic and inflammatory. When the skin's natural barrier is breached, microorganisms can enter the body and cause poor temperature regulation, fluid loss, and invasion. Intravascular volume loss is typically worsened by injured or edematous tissues. Significant heat loss may occur from the wounded dermis' lack of thermoregulation, particularly in exposed wounds. The severity determines the different treatments. Serious burns require considerable care, while lesser burns just require cleaning and painkillers. Just-partially thickened burns must be cleansed with soap and water before being clothed. For full-thickness burns, surgery, including skin grafting, is frequently required. Extensive intravenous fluid doses are often required to treat serious burns resulting from tissue edema and capillary fluid leakage.

Determination of energy requirements after minor burns using indirect calorimetry: A descriptive cohort study.

BACKGROUND: Minor burns could be associated with moderate hypermetabolism. In this study, the primary outcome was measured energy expenditure (mEE) determined by indirect calorimetry in patients with minor burns. We also compared mEE with predictive values and actual energy intakes. METHODS: Adults with minor burns exclusively treated on an outpatient basis were included. During the week following injury, a dietitian performed indirect calorimetry (Q-NRG in canopy mode), calculated the estimated energy expenditure (eEE) based on the Harris-Benedict (HB) and Henry formulas, and evaluated daily energy intakes using a food anamnesis. RESULTS: Forty-nine patients (59.2% male; median age: 35 [interquartile range: 29-46.5] years; body mass index [BMI]: 26.2 [22.3-29.6] kg/m2; burn surface area [BSA]: 1.5% [1%-2%]) were included 4 (2-6) days after injury. The mEE was 1863 (1568-2199) kcal or 25 (22.4-28.5) kcal/kg and 1838 (1686-2026) kcal or 26.1 (23.7-27.7) kcal/kg in patients who were respectively fasting for >10 h or not (P = 0.991 or P = 0.805). The total mEE was 104% (95%-116%) and 108% (99%-122%) of the total eEE using the HB and Henry formulas, respectively, with diet-induced thermogenesis and physical activity level. Hypermetabolism (ie, oxygen consumption at rest ≥3.5 ml/kg/min) was observed in 21/49 (42.9%) patients. Energy intakes corresponded to 71% (60%-86%) of the total mEE. CONCLUSION: Performing indirect calorimetry in adults with minor burns revealed that ≥40% of the tested adults presented a hypermetabolism and that their mEE was not covered by their energy intakes.

H+-slip correlated to rotor free-wheeling as cause of F1FO-ATPase dysfunction in primary mitochondrial disorders.

Inborn errors of metabolism are related to mitochondrial disorders caused by dysfunction of the oxidative phosphorylation (OXPHOS) system. Congenital hypermetabolism in the infant is a rare disease belonging to Luft syndrome, nonthyroidal hypermetabolism, arising from a singular example of a defect in OXPHOS. The mitochondria lose coupling of mitochondrial substrates oxidation from the ADP phosphorylation. Since Luft syndrome is due to uncoupled cell respiration responsible for deficient in ATP production that originates in the respiratory complexes, a de novo heterozygous variant in the catalytic subunit of mitochondrial F1FO-ATPase arises as the main cause of an autosomal dominant syndrome of hypermetabolism associated with dysfunction in ATP production, which does not involve the respiratory complexes. The F1FO-ATPase works as an embedded molecular machine with a rotary action using two different motor engines. The FO, which is an integral domain in the membrane, dissipates the chemical potential difference for H+, a proton motive force (Δp), across the inner membrane to generate a torsion. The F1 domain-the hydrophilic portion responsible for ATP turnover-is powered by the molecular rotary action to synthesize ATP. The structural and functional coupling of F1 and FO domains support the energy transduction for ATP synthesis. The dissipation of Δp by means of an H+ slip correlated to rotor free-wheeling of the F1FO-ATPase has been discovered to cause enzyme dysfunction in primary mitochondrial disorders. In this insight, we try to offer commentary and analysis of the molecular mechanism in these impaired mitochondria.

Subcutaneous white adipose tissue independently regulates burn-induced hypermetabolism via immune-adipose crosstalk.

Severe burns induce a chronic hypermetabolic state that persists well past wound closure, indicating that additional internal mechanisms must be involved. Adipose tissue is suggested to be a central regulator in perpetuating hypermetabolism, although this has not been directly tested. Here, we show that thermogenic adipose tissues are activated in parallel to increases in hypermetabolism independent of cold stress. Using an adipose tissue transplantation model, we discover that burn-derived subcutaneous white adipose tissue alone is sufficient to invoke a hypermetabolic response in a healthy recipient mouse. Concomitantly, transplantation of healthy adipose tissue alleviates metabolic dysfunction in a burn recipient. We further show that the nicotinic acetylcholine receptor signaling pathway may mediate an immune-adipose crosstalk to regulate adipose tissue remodeling post-injury. Targeting this pathway could lead to innovative therapeutic interventions to counteract hypermetabolic pathologies.

Ambient Room Temperatures in a Burn Intensive Care Unit-A Quality Improvement Project.

Introduction: Patients with major burn injuries are particularly susceptible to hypothermia. The ability to maintain and rapidly increase ambient temperatures may reduce the impact of hypothermia and the hypermetabolic response. The purpose of this study was to determine ambient patient room temperatures in a burn intensive care unit (ICU) and to evaluate our ability to adjust these temperatures. Methods: The ambient temperatures of 9 burn ICU patient rooms were recorded hourly over a 6-month period in an American Burn Association-verified burn centre. Temperatures were recorded using wall-mounted smart sensors, transmitted to a mobile smartphone application via Bluetooth, and then exported to Excel for analysis. On 2 predetermined dates, thermostats in all rooms were simultaneously set to maximum, and monitored over 3 h. This represented a sound change initiative, and replicated a medical order to increase the ambient temperature during critical stages of patient care. Results: We recorded 4394 individual hourly temperature measurements for each of the 9 rooms. The mean ambient temperature was 23.5 ± 0.3 °C (range 22.8-24). After intervention 1, ambient temperatures increased <2 °C in 7 rooms and by only 2 °C-3 °C in the other 2 rooms. The overall mean increase in temperature over 3 h across all rooms was 1.03 °C ± 1.19 °C (range -0.88 to 3.26). Following intervention 2, temperatures could be increased by ≥2 °C in only 2 rooms with an overall mean increase in temperature of only 0.76 °C ± 0.99 °C (range -0.29 to 2.43) across all rooms. Conclusions: The burn ICU rooms were relatively cool and our ability locally to adjust ambient temperatures quickly was limited. Burn centres should have regular facility assessments to assess whether ambient temperatures can be adjusted expeditiously when required.

Introduction : Les patients ayant des brûlures importantes (>20% de la surface corporelle totale) sont particulièrement exposés au risque d'hypothermie. La capacité à maintenir et à rapidement augmenter la température ambiante peut réduire la répercussion négative de l'hypothermie et de la réponse hypermétabolique. L'objectif de cette étude était de déterminer la température ambiante des chambres de patients dans une unité de soins intensifs (USI) pour brûlés et d'évaluer notre capacité à ajuster ces températures. Méthodes : La température ambiante de neuf chambres de patients en USI pour brûlés a été enregistrée heure par heure pendant une période de 6 mois dans un centre pour brûlés vérifié par l'ABA. Les températures ont été consignées en utilisant des capteurs intelligents montés sur les murs avec transmission par Bluetooth à une application mobile pour téléphone intelligent, puis exportées dans un tableau Excel pour analyse. À deux dates prédéterminées, les thermostats de toutes les chambres ont été simultanément réglés au maximum et contrôlés pendant 3 heures. Cela représentait une initiative de changement réfléchie, répliquant une consigne médicale d'augmentation de la température ambiante pendant les phases critiques de soins aux patients. Résultats : Nous avons enregistré 4394 relevés horaires de la température pour chacune des neuf chambres. La température ambiante moyenne était de 23,5 ± 0,3 °C (écart : 22,8 à 24). Après la première intervention, les températures ambiantes ont augmenté de moins de 2 °C dans 7 chambres et de seulement 2 °C à 3 °C dans les deux autres chambres. L'augmentation moyenne globale pendant les 3 heures dans toutes les chambres était de 1,03 °C ± 1,19 °C (écart : −0,88 à 3,26). Après la deuxième intervention, les températures ont pu être augmentées de ≥ 2 °C dans seulement deux chambres avec une augmentation globale moyenne de la température de seulement 0,76 °C ± 0,99 °C (écart : −0,29 à 2,43) pour l'ensemble des chambres. Conclusions : Les chambres de l'USI pour brûlés étaient relativement fraîches et notre capacité à ajuster rapidement les températures ambiantes était limitée. Les centres pour brûlés devraient faire l'objet d'évaluations régulières d'établissement pour déterminer si la température ambiante peut être ajustée dans des délais très brefs en cas de besoin.

A critical view of the use of predictive energy equations for the identification of hypermetabolism in motor neuron disease: A pilot study.

BACKGROUND AND AIMS: People living with motor neuron disease (MND) frequently struggle to consume an optimal caloric intake. Often compounded by hypermetabolism, this can lead to dysregulated energy homeostasis, prompting the onset of malnutrition and associated weight loss. This is associated with a poorer prognosis and reduced survival. It is therefore important to establish appropriate nutritional goals to ensure adequate energy intake. This is best done by measuring resting energy expenditure (mREE) using indirect calorimetry. However, indirect calorimetry is not widely available in clinical practice, thus dietitians caring for people living with MND frequently use energy equations to predict resting energy expenditure (pREE) and estimate caloric requirements. Energy prediction equations have previously been shown to underestimate resting energy expenditure in over two-thirds of people living with MND. Hypermetabolism has previously been identified using the metabolic index. The metabolic index is a ratio of mREE to pREE, whereby an increase of mREE by ≥110% indicates hypermetabolism. We aim to critically reflect on the use of the Harris-Benedict (1919) and Henry (2005) energy prediction equations to inform a metabolic index to indicate hypermetabolism in people living with MND. METHODS: mREE was derived using VO2 and VCO2 measurements from a GEMNutrition indirect calorimeter. pREE was estimated by Harris-Benedict (HB) (1919), Henry (2005) and kcal/kg/day predictive energy equations. The REE variation, described as the percentage difference between mREE and pREE, determined the accuracy of pREE ([pREE-mREE]/mREE) x 100), with accuracy defined as ≤ ± 10%. A metabolic index threshold of ≥110% was used to classify hypermetabolism. All resting energy expenditure data are presented as kcal/24hr. RESULTS: Sixteen people living with MND were included in the analysis. The mean mREE was 1642 kcal/24hr ranging between 1110 and 2015 kcal/24hr. When REE variation was analysed for the entire cohort, the HB, Henry and kcal/kg/day equations all overestimated REE, but remained within the accuracy threshold (mean values were 2.81% for HB, 4.51% for Henry and 8.00% for kcal/kg/day). Conversely, inter-individual REE variation within the cohort revealed HB and Henry equations both inaccurately reflected mREE for 68.7% of participants, with kcal/kg/day inaccurately reflecting 41.7% of participants. Whilst the overall cohort was not classified as hypermetabolic (mean values were 101.04% for HB, 98.62% for Henry and 95.64% for kcal/kg/day), the metabolic index ranges within the cohort were 70.75%-141.58% for HB, 72.82%-127.69% for Henry and 66.09%-131.58% for kcal/kg/day, indicating both over- and under-estimation of REE by these equations. We have shown that pREE correlates with body weight (kg), whereby the lighter the individual, the greater the underprediction of REE. When applied to the metabolic index, this underprediction biases towards the classification of hypermetabolism in lighter individuals. CONCLUSION: Whilst predicting resting energy expenditure using the HB, Henry or kcal/kg/day equations accurately reflects derived mREE at group level, these equations are not suitable for informing resting energy expenditure and classification of hypermetabolism when applied to individuals in clinical practice.

Plasma oxylipin profiling by high resolution mass spectrometry reveal signatures of inflammation and hypermetabolism in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of motor neurons, systemic hypermetabolism, and inflammation. In this context, oxylipins have been investigated as signaling molecules linked to neurodegeneration, although their specific role in ALS remains unclear. Importantly, most methods focused on oxylipin analysis are based on low-resolution mass spectrometry, which usually confers high sensitivity, but not great accuracy for molecular characterization, as provided by high-resolution MS (HRMS). Here, we established an ultra-high performance liquid chromatography HRMS (LC-HRMS) method for simultaneous analysis of 126 oxylipins in plasma. Intra- and inter-day method validation showed high sensitivity (0.3-25 pg), accuracy and precision for more than 90% of quality controls. This method was applied in plasma of ALS rats overexpressing the mutant human Cu/Zn-superoxide dismutase gene (SOD1-G93A) at asymptomatic (ALS 70 days old) and symptomatic stages (ALS 120 days old), and their respective age-matched wild type controls. From the 56 oxylipins identified in plasma, 17 species were significantly altered. Remarkably, most of oxylipins linked to inflammation and oxidative stress derived from arachidonic acid (AA), like prostaglandins and mono-hydroxides, were increased in ALS 120 d rats. In addition, ketones derived from AA and linoleic acid (LA) were increased in both WT 120 d and ALS 120 d groups, supporting that age also modulates oxylipin metabolism in plasma. Interestingly, the LA-derived diols involved in fatty acid uptake and ß-oxidation, 9(10)-DiHOME and 12(13)-DiHOME, were decreased in ALS 120 d rats and showed significant synergic effects between age and disease factors. In summary, we validated a high-throughput LC-HRMS method for oxylipin analysis and provided a comprehensive overview of plasma oxylipins involved in ALS disease progression. Noteworthy, the oxylipins altered in plasma have potential to be investigated as biomarkers for inflammation and hypermetabolism in ALS.

A mechanistic account of visual discomfort.

Much of the neural machinery of the early visual cortex, from the extraction of local orientations to contextual modulations through lateral interactions, is thought to have developed to provide a sparse encoding of contour in natural scenes, allowing the brain to process efficiently most of the visual scenes we are exposed to. Certain visual stimuli, however, cause visual stress, a set of adverse effects ranging from simple discomfort to migraine attacks, and epileptic seizures in the extreme, all phenomena linked with an excessive metabolic demand. The theory of efficient coding suggests a link between excessive metabolic demand and images that deviate from natural statistics. Yet, the mechanisms linking energy demand and image spatial content in discomfort remain elusive. Here, we used theories of visual coding that link image spatial structure and brain activation to characterize the response to images observers reported as uncomfortable in a biologically based neurodynamic model of the early visual cortex that included excitatory and inhibitory layers to implement contextual influences. We found three clear markers of aversive images: a larger overall activation in the model, a less sparse response, and a more unbalanced distribution of activity across spatial orientations. When the ratio of excitation over inhibition was increased in the model, a phenomenon hypothesised to underlie interindividual differences in susceptibility to visual discomfort, the three markers of discomfort progressively shifted toward values typical of the response to uncomfortable stimuli. Overall, these findings propose a unifying mechanistic explanation for why there are differences between images and between observers, suggesting how visual input and idiosyncratic hyperexcitability give rise to abnormal brain responses that result in visual stress.

Cellular allostatic load is linked to increased energy expenditure and accelerated biological aging.

Stress triggers anticipatory physiological responses that promote survival, a phenomenon termed allostasis. However, the chronic activation of energy-dependent allostatic responses results in allostatic load, a dysregulated state that predicts functional decline, accelerates aging, and increases mortality in humans. The energetic cost and cellular basis for the damaging effects of allostatic load have not been defined. Here, by longitudinally profiling three unrelated primary human fibroblast lines across their lifespan, we find that chronic glucocorticoid exposure increases cellular energy expenditure by ∼60%, along with a metabolic shift from glycolysis to mitochondrial oxidative phosphorylation (OxPhos). This state of stress-induced hypermetabolism is linked to mtDNA instability, non-linearly affects age-related cytokines secretion, and accelerates cellular aging based on DNA methylation clocks, telomere shortening rate, and reduced lifespan. Pharmacologically normalizing OxPhos activity while further increasing energy expenditure exacerbates the accelerated aging phenotype, pointing to total energy expenditure as a potential driver of aging dynamics. Together, our findings define bioenergetic and multi-omic recalibrations of stress adaptation, underscoring increased energy expenditure and accelerated cellular aging as interrelated features of cellular allostatic load.

Resting energy expenditure measured by indirect calorimetry in mechanically ventilated patients during ICU stay and post-ICU hospitalization: A prospective observational study.

PURPOSE: The metabolic course during and after critical illness is unclear. We performed repeated indirect calorimetry (IC) measurements during ICU- and post-ICU hospitalization to determine resting energy expenditure (REE). METHODS: Prospective observational design. In ventilated ICU patients, IC measurements were performed every three days until hospital discharge. Measured REE as predicted by the Harris-Benedict equation (HBE-REE) and 25 kcal/adjusted body weight/day (25-REE) were compared. RESULTS: In 56 patients (38% females, 71[13]years, BMI 29(27;31)kg/m2), 189 ICU IC measurements were performed. Measured REE did not differ from HBE-REE at ICU admission, but was lower than 25-REE. Measured REE was increased compared to baseline on ICU-admission-day four (29(29-30)kcal/kg/day; mean difference 3.1(1.4-4.9)kcal/kg/day, p < 0.001) and thereafter during ICU admission. During post-ICU ward stay, 44 measurements were performed in 23 patients, showing a higher mean REE than during ICU stay (33(31-35)kcal/kg/day; mean difference 2.6(1.2-3.9)kcal/kg/day, p < 0.001). The REE in the ICU and ward was >110% of HBE-REE from day four onwards. CONCLUSIONS: Critically ill mechanically ventilated patients were shown to have a resting energy expenditure (REE) > 110% of predicted REE on ICU admission day four and thereafter. Indirect calorimetry measurements suggest that the mean energy requirements during post-ICU hospitalization are higher than those in the ICU.

Real world experience of therapeutic monitoring of medically treated prosthetic valve infective endocarditis by 18F-FDG-PET/CT.

INTRODUCTION: 18F-FDG-PET/CT is recommended to improve the diagnosis of prosthetic valve infective endocarditis (PVIE) and is a major criterion in the ESC-2015 classification. However, there is little evidence for its usefulness in the follow-up of medically treated PVIE patients. METHODS: A monocentric retrospective analysis of patients hospitalized for PVIE between January 2013 and December 2019 who were not treated with surgery and who had at least two 18F-FDG-PET/CT examinations during their medical management. RESULTS: Among 170 patients with PVIE, 117 were treated with antibiotic therapy but no surgery. Of these, 36 (31%) had at least two 18F-FDG-PET/CT examinations. At initial imaging, 28 patients had heterogeneous FDG uptake on their prosthetic valve and eight on their associated aortic graft. Hypermetabolism of spleen and bone marrow (HSBM) was observed in 18 and 19 patients, respectively. At the first follow-up 18F-FDG-PET/CT, 21 (58%) patients still had heterogeneous uptake, indicating persistent active endocarditis. HSBM was still present at the last follow-up imaging in four of the six patients with recurrent PVIE. CONCLUSION: 18F-FDG-PET/CT monitoring of medically treated patients with PVIE provides valuable additional information and prospective multicentric study should be conducted to assess its usefulness.

Lactate shuttling drives the browning of white adipose tissue after burn.

High levels of plasma lactate are associated with increased mortality in critically injured patients, including those with severe burns. Although lactate has long been considered a waste product of glycolysis, it was recently revealed that it acts as a potent inducer of white adipose tissue (WAT) browning, a response implicated in mediating postburn cachexia, hepatic steatosis, and sustained hypermetabolism. Despite the clinical presentation of hyperlactatemia and browning in burns, whether these two pathological responses are linked is currently unknown. Here, we report that elevated lactate plays a causal signaling role in mediating adverse outcomes after burn trauma by directly promoting WAT browning. Using WAT obtained from human burn patients and mouse models of thermal injury, we show that the induction of postburn browning is positively correlated with a shift toward lactate import and metabolism. Furthermore, daily administration of l-lactate is sufficient to augment burn-induced mortality and weight loss in vivo. At the organ level, increased lactate transport amplified the thermogenic activation of WAT and its associated wasting, thereby driving postburn hepatic lipotoxicity and dysfunction. Mechanistically, the thermogenic effects of lactate appeared to result from increased import through MCT transporters, which in turn increased intracellular redox pressure, [NADH/NAD+], and expression of the batokine, FGF21. In fact, pharmacological inhibition of MCT-mediated lactate uptake attenuated browning and improved hepatic function in mice after injury. Collectively, our findings identify a signaling role for lactate that impacts multiple aspects of postburn hypermetabolism, necessitating further investigation of this multifaceted metabolite in trauma and critical illness.NEW & NOTEWORTHY To our knowledge, this study was the first to investigate the role of lactate signaling in mediating white adipose tissue browning after burn trauma. We show that the induction of browning in both human burn patients and mice is positively correlated with a shift toward lactate import and metabolism. Daily l-lactate administration augments burn-induced mortality, browning, and hepatic lipotoxicity in vivo, whereas pharmacologically targeting lactate transport alleviates burn-induced browning and improves liver dysfunction after injury.

Hypermetabolism in mice carrying a near-complete human chromosome 21.

The consequences of aneuploidy have traditionally been studied in cell and animal models in which the extrachromosomal DNA is from the same species. Here, we explore a fundamental question concerning the impact of aneuploidy on systemic metabolism using a non-mosaic transchromosomic mouse model (TcMAC21) carrying a near-complete human chromosome 21. Independent of diets and housing temperatures, TcMAC21 mice consume more calories, are hyperactive and hypermetabolic, remain consistently lean and profoundly insulin sensitive, and have a higher body temperature. The hypermetabolism and elevated thermogenesis are likely due to a combination of increased activity level and sarcolipin overexpression in the skeletal muscle, resulting in futile sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) activity and energy dissipation. Mitochondrial respiration is also markedly increased in skeletal muscle to meet the high ATP demand created by the futile cycle and hyperactivity. This serendipitous discovery provides proof-of-concept that sarcolipin-mediated thermogenesis via uncoupling of the SERCA pump can be harnessed to promote energy expenditure and metabolic health.