Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Background: Hemodynamic support using vasoactive agents is a mainstay in the management of patients with pediatric fluid-refractory septic shock (FRSS). However, evidence supporting the appropriate choice of vasoactive agent is limited. This study aimed to perform a systematic review and meta-analysis on the effect of different first-line vasoactive strategies on mortality in pediatric FRSS. ⋯ Interpretation: Among children with FRSS receiving a single vasoactive agent, norepinephrine was associated with the lowest mortality rate. Comparing dopamine and epinephrine, patients receiving epinephrine needed less mechanical ventilation and showed a trend for lower mortality rate. Further research is needed to better delineate the first-line vasoactive agent in this population.
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Observational Study
Impact of ABCC8 and TRPM4 genetic variation in central nervous system dysfunction associated with pediatric sepsis.
Background: Sepsis-associated brain injury is associated with deterioration of mental status, persistent cognitive impairment, and morbidity. The SUR1/TRPM4 channel is a nonselective cation channel that is transcriptionally upregulated in the central nervous system with injury, allowing sodium influx, depolarization, cellular swelling, and secondary injury. We hypothesized that genetic variation in ABCC8 (SUR1 gene) and TRPM4 would associate with central nervous system dysfunction in severe pediatric sepsis. ⋯ Structural mapping showed that rare variants concentrated in the nucleotide-binding domains of ABCC8 and N-terminal melastatin homology region of TRPM4. Conclusion : This study suggests a role for the ABCC8/TRPM4 channel in central nervous system dysfunction in severe pediatric sepsis. Although exploratory, the lack of therapies to prevent or mitigate central nervous system dysfunction in pediatric sepsis warrants further studies to clarify the mechanism and confirm the potential protective effect of these rare ABCC8/TRPM4 variants.
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Background: Recent observational studies have suggested that osteoporosis may be a risk factor for sepsis. To mitigate confounding factors and establish the causal relationship between sepsis and osteoporosis, we conducted a two-sample Mendelian randomization analysis using publicly available summary statistics. Methods: Utilizing summary data from FinnGen Biobank, we employed a two-sample Mendelian randomization (MR) analysis to predict the causal relationship between osteoporosis and sepsis. ⋯ Conversely, an increase of one standard deviation in sepsis was associated with a 26% increased risk of osteoporosis, with an OR of 1.26 (95% CI, 1.11-1.16; P = 0.45E-03). BWMR yielded an OR of 1.26 (95% CI, 1.09-1.45; P = 1.45E-03), supporting sepsis as a risk factor for osteoporosis. Conclusion: There is an association between osteoporosis and sepsis, with osteoporosis serving as a risk factor for the development of sepsis, while sepsis may also promote the progression of osteoporosis.
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Background : Trauma and blood loss are frequently associated with organ failure, immune dysfunction, and a high risk of secondary bacterial lung infections. We aim to test if plasma metabolomic flux and monocyte bioenergetics are altered in association with trauma and related secondary infections. Methods : Plasma samples were collected from trauma patients at three time points: days 0, 3, and 7 postadmission. ⋯ Conclusions : Our study highlights that the metabolic profile is significantly and persistently affected by trauma and related infections. Among trauma survivors, metabolic alterations in plasma were associated with reduced monocyte bioenergetics. These exploratory findings establish a groundwork for future clinical studies aimed at enhancing our understanding of the interplay between metabolic/bioenergetic alterations associated with trauma and secondary bacterial infections.
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Postpartum hemorrhage is the leading cause of preventable maternal illness and death globally and carries a disproportionately high burden of mortality in low- to middle-income countries. Tranexamic acid, an antifibrinolytic drug, has been widely adopted to control bleeding in trauma and other surgical conditions. ⋯ However, despite these guidelines and the proven utility of tranexamic acid to treat postpartum hemorrhage, widespread adoption of tranexamic acid into global standards of care across professional organizations has not been achieved. It is important for healthcare providers to understand the etiologies of postpartum hemorrhage, the mechanism of action and adverse effect profile of tranexamic acid, and the available literature regarding the use of tranexamic acid to prevent and treat postpartum hemorrhage to provide the best care for the pregnant patient.