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: 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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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.
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Introduction: Sepsis is a dysregulated host response to infection that can lead to life-threatening organ dysfunction. Clinical and animal studies consistently demonstrate that female subjects are less susceptible to the adverse effects of sepsis, demonstrating the importance of understanding how sex influences sepsis outcomes. The signal transducer and activator of transcription 3 (STAT3) pathway are a major signaling pathway that facilitates inflammation during sepsis. ⋯ Conclusions: Our study demonstrates that sex influences white adipose tissue STAT3 activation and morphology during sepsis, which is not dependent on the presence of functional STAT3 in mature adipocytes. Furthermore, genetic inhibition of adipocyte STAT3 activation in male, but not female mice, results in reduced lung neutrophil infiltration and lung injury during sepsis. The results from our study demonstrate the importance of considering biological sex and the white adipose tissue as potential sources and targets of inflammation during sepsis.
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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.