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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Objective: To identify and describe characteristics of patients with sepsis who could be treated with minimally invasive sepsis (MIS) approach without intensive care unit (ICU) admission and to develop a prediction model to select candidates for MIS approach. Methods: A secondary analysis of the electronic database of patients with sepsis at Mayo Clinic, Rochester, MN. Candidates for the MIS approach were adults with septic shock and less than 48 hours of ICU stay, who did not require advanced respiratory support and were alive at hospital discharge. ⋯ The MIS score cutoff of 3 resulted in a model odds ratio of 0.15 (95% confidence interval, 0.08-0.28) and a negative predictive value of 91% (95% confidence interval, 88.69-92.92). Conclusions: This study identifies a subset of low-risk septic shock patients who can potentially be managed outside the ICU. Once validated in an independent, prospective sample our prediction model can be used to identify candidates for MIS approach.
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While fluid resuscitation is fundamental in the treatment of sepsis-induced tissue hypoperfusion, a sustained positive fluid balance is associated with excess mortality. Hyaluronan, an endogenous glycosaminoglycan with high affinity to water, has not been tested previously as adjuvant to fluid resuscitation in sepsis. In a prospective, parallel-grouped, blinded model of porcine peritonitis sepsis, we randomized animals to intervention with adjuvant hyaluronan (add-on to standard therapy, n = 8) or 0.9% saline (n = 8). ⋯ Plasma IL-6 increased to 2,450 (1,420-6,890) pg/mL and 3,690 (1,410-11,960) pg/mL (18 hours of resuscitation) in the intervention and control groups (nonsignificant). The intervention counteracted the increase in proportion of fragmented hyaluronan associated with peritonitis sepsis (mean peak elution fraction [18 hours of resuscitation] intervention group: 16.8 ± 0.9 versus control group: 17.9 ± 0.6 [ P = 0.031]). In conclusion, hyaluronan did not reduce the volume needed for fluid resuscitation or decrease the inflammatory reaction, even though it counterbalanced the peritonitis-induced shift toward increased proportion of fragmented hyaluronan.
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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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Background: Infantile pneumonia is a respiratory infection disease, seriously threatening the life of neonatal patients. Circular RNA (circRNA) dysregulation is reported to be involved in pneumonia pathogenesis. Circ_0012535 was previously displayed to be upregulated in blood samples of patients with community-acquired pneumonia. ⋯ MiR-338-3p bound to IL6R 3'UTR, and circ_0012535 shared miR-338-3p binding site with IL6R. IL6R overexpression reversed the role of miR-338-3p, thereby recovering LPS-induced WI38 cell apoptosis and inflammation. Conclusion: Circ_0012535 supported LPS-induced WI38 cell apoptosis and inflammation to promote the progression of infantile pneumonia, and circ_0012535 functioned partly by targeting the miR-338-3p/IL6R signaling.
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Pulmonary epithelial barrier injury contributes to acute lung injury, accelerating exudate formation, and resulting alveolar edema. Heme oxygenase-1 (HO-1) plays an important role in ameliorating the pathological symptoms of acute lung injury (ALI). Using an ALI mouse model induced by LPS inhalation, the present study explored the potential molecular regulatory effect of hemin (a potent HO-1 inducer) against ALI epithelial damage. ⋯ Furthermore, HO-1 elevation inhibited the activation of the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome and oxidative stress in alveolar epithelia, leading to the suppression of inflammatory responses and epithelial pyroptosis, as indicated by the decreased levels of NLRP3 and apoptosis-associated speck-like protein containing a CARD domain (ASC), repressed cleavage of caspase-1 and gasdermin D, and reduced expression levels of inflammatory cytokine IL-1β. In contrast, protoporphyrin IX zinc (II) (ZnPP, an HO-1 inhibitor) treatment had no protective effect on LPS inhalation-induced ALI in mice. In summary, HO-1 induction serves a critical role in maintaining airway epithelium homeostasis through the inhibition of NLRP3/ASC/caspase-1-mediated pyroptosis and inflammation in the occurrence of ALI.