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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Observational Study
Global signatures of the microbiome and metabolome during hospitalization of septic patients.
Background: The gut plays an important role in the development of sepsis and acts as one of the possible drivers of multiple-organ dysfunction syndrome. This study aimed to explore the dynamic alterations in the gut microbiota and its metabolites in septic patients at different stages of intensive care unit (ICU) admission. Methods: In this prospective observational study, a total of 109 fecal samples from 23 septic patients, 16 nonseptic ICU patients and 10 healthy controls were analyzed. 16S rRNA gene sequencing and ultra-performance liquid chromatography coupled to tandem mass spectrometry targeted metabolomics were used for microbiota and metabolome analysis. ⋯ In the nomogram model, the higher abundance of Klebsiella , concentration of taurocholic acid, and Sequential Organ Failure Assessment score, combined with a lower butyric acid concentration, could predict a higher probability of death from sepsis. Conclusions: Our study indicated that the dynamical alterations of gut microbiota and its metabolites were associated with the prognosis of the sepsis. Based on these alterations and clinical indicators, a nomogram model to predict the prognosis of septic patients was performed.
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Objective: The aim of the study is to evaluate the efficacy and safety of using angiotensin II (Ang2) as primary vasopressor for vasodilatory hypotension. Methods: This was a prospective observational study of critically ill adults admitted to an academic intensive care unit (ICU) with vasodilatory hypotension. We treated 40 patients with Ang2 as primary vasopressor and compared them with 80 matched controls who received conventional vasopressors (norepinephrine, vasopressin, metaraminol, epinephrine, or combinations). ⋯ The incidence of thromboembolic complications was similar. Conclusions: Primary Ang2 administration in vasodilatory hypotension did not seem harmful compared with conventional vasopressors. Although Ang2 did not decrease peak serum creatinine levels or major adverse kidney events, its effects on intensive care unit survival, serum troponin, and renal function in patients on renin angiotensin aldosterone system inhibitors warrant further exploration in randomized trials (ACTRN12621000281897).
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Background: Immunosuppression caused by immune cell apoptosis and an imbalance of T helper 2 cells (T H 2) and T helper 1 cells (T H 1), is associated with poor outcomes in septic patients. Esmolol was reported to improve survival by modulating immune responses in septic shock. Whether esmolol could alleviate sepsis-induced immunosuppression and the optimal dose are unclear. ⋯ Conclusions: Low dose of esmolol reduced T-lymphocyte apoptosis and restored T H 2/T H 1 ratio in septic shock. Esmolol might modulate Akt/Bcl-2/Caspase-3 pathway to relieve T-lymphocyte apoptosis and inhibit Erk1/2 activity to decrease T H 0 differentiation to T H 2. Esmolol may be a potential immunoregulator of septic shock.
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Introduction: Cell-free DNA (CFDNA) has emerged as a prognostic biomarker in patients with sepsis. Circulating CFDNA is hypothesized to be associated with histones in the form of nucleosomes. In vitro, DNA activates coagulation and inhibits fibrinolysis, whereas histones activate platelets and are cytotoxic to endothelial cells. ⋯ Monotherapies may be improving survival by reducing blood bacterial loads, citrullinated histone-H3, and thrombin-antithrombin complexes, and improving protein C levels. Conclusions: Compared with saline- and combination-treated mice, administration of monotherapies to septic mice improved survival. These findings suggest that there may be a negative drug-drug interaction between DNase I and LMWH when DNase I is administered intraperitoneally in a murine model of polymicrobial abdominal sepsis.
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Background: The importance of circular RNA (circRNA) in the progression of septic acute kidney injury (AKI) was gradually recognized. It has been confirmed that circ_0008882 expression was decreased in the blood of patients with AKI. However, the role of circ_0008882 in septic AKI progression remains unclear. ⋯ MiR-155-5p was a target of circ_0008882, and miR-155-5p mimic restored circ_0008882 overexpression-mediated effects on LPS-treated HK2 cells. PDE7A was identified as a target gene of miR-155-5p, and PDE7A downregulation almost reverted the improvement impacts induced by the miR-155-5p inhibitor. Conclusions: Overexpression of circ_0008882 impeded LPS-induced HK2 cell injury by modulating miR-155-5p/PDE7A pathway, implying that circ_0008882 might be a possible circRNA-targeted therapy for septic AKI.