Mitochondrial dysfunction plays a role in the pathophysiology of sepsis-related organ failure, and its role in pediatric febrile illness remains largely unexplored. The study by Sartori et al. uses a prospective design comparing febrile patients from both Emergency Department and ICU with appropriate controls. It is important to note that while this study was prospective for the Emergency Department patients with febrile illness, the sepsis data represents a secondary analysis of a previous study, which may limit direct comparisons between these groups. Mitochondrial function was evaluated using spare respiratory capacity (SRC), citrate synthase (CS) activity and mitochondrial to nuclear DNA ratio (mtDNA: nDNA) in peripheral blood mononuclear cells (PBMCs). A significant reduction in SRC was noted in both febrile illness and sepsis associated with lower CS activity. Interestingly, significantly lower mtDNA:nDNA ratio was noted in febrile illness compared to both ED/PICU controls and sepsis patients. Future studies should focus on assessment of mitochondrial function longitudinally and in individual cell types while trying to identify newer markers of mitochondrial dysfunction. Long term goal of discovering targeted mitochondrial therapy could improve survival in fatal illness including sepsis as we move closer to more personalized and effective treatment strategies for these critical conditions.
AbstractSection Impact-
The study compared mitochondrial function in children with febrile illness, sepsis, and controls, but sepsis patients were from a different cohort (ICU) than febrile illness patients (ED), potentially limiting direct comparisons.
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A significant reduction in mitochondrial spare respiratory capacity noted in both febrile illness and sepsis associated with a trend towards lower citrate synthase activity.
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Further studies are required to understand the contrasting mitochondrial profiles in various pathological conditions.
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Sudhadevi, T., Harijith, A. Mitochondrial dysfunction in febrile illness and sepsis: no clear picture yet. Pediatr Res (2024). https://doi.org/10.1038/s41390-024-03696-1
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DOI: https://doi.org/10.1038/s41390-024-03696-1
