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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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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Randomized Controlled Trial Multicenter Study
Evaluation of Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Septic Shock: A Randomized Controlled Trial (The HYVITS Trial).
Purpose: The aim of the study is to evaluate the effect of combined hydrocortisone, vitamin C, and thiamine (triple therapy) on the mortality of patients with septic shock. Methods : This multicenter, open-label, two-arm parallel-group, randomized controlled trial was conducted in four intensive care units in Qatar. Adult patients diagnosed with septic shock requiring norepinephrine at a rate of ≥0.1 μg/kg/min for ≥6 h were randomized to a triple therapy group or a control group. ⋯ Conclusion: Triple therapy did not improve in-hospital mortality at 60 days in critically ill patients with septic shock or reduce the vasopressor duration or SOFA score at 72 h. Trial Registration:ClinicalTrials.gov identifier: NCT03380507. Registered on December 21, 2017.
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Objective: Based on the functions of immunoregulation and signal transduction, septic peripheral blood sequencing and bioinformatics technology were used to screen potential core targets. Methods: Peripheral blood of 23 patients with sepsis and 10 normal volunteers underwent RNA-seq processing within 24 hours after admission to the hospital. Data quality control and differential gene screening were performed based on R language ( P < 0.01; log2FC ≥ 2). ⋯ Conclusions: CD160, KLRG1, S1PR5, and RGS16 were mainly located in human peripheral blood NK-T cells. Sepsis participants expressed lower levels of S1PR5, CD160, and KLRG1, while sepsis participants expressed higher levels of RGS16. This suggests that they may be potential research targets for sepsis.
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Multicenter Study
OUTCOMES FOLLOWING ZONE 3 AND ZONE 1 AORTIC OCCLUSION FOR THE TREATMENT OF BLUNT PELVIC INJURIES.
Background: A 2021 report of the Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery multicenter registry described the outcomes of patients treated with Zone 3 resuscitative endovascular balloon occlusion of the aorta (REBOA zone 3). Our study builds upon that report, testing the hypothesis that REBOA zone 3 is associated with better outcomes than REBOA Zone 1 in the immediate treatment of severe, blunt pelvic injuries. Methods: We included adults who underwent aortic occlusion (AO) via REBOA zone 1 or REBOA Zone 3 in the emergency department for severe, blunt pelvic injuries [Abbreviated Injury Score ≥ 3 or pelvic packing/embolization/first 24 hours] in institutions with >10 REBOAs. ⋯ These patients did not differ in systolic blood pressure (SBP), cardiopulmonary resuscitation in the prehospital/hospital settings, SBP at the start of AO, time to AO start, likelihood of achieving hemodynamic stability or requirement of a second AO. After controlling for confounders, compared with REBOA Zone 3, REBOA Zone 1 was associated with a significantly higher mortality (adjusted hazard ratio, 1.51; 95% confidence interval [CI], 1.04-2.19), but there were no differences in VFD > 0 (adjusted relative risk, 0.66; 95% CI, 0.33-1.31), IFD > 0 (adjusted relative risk, 0.78; 95% CI, 0.39-1.57), discharge GCS (adjusted difference, -1.16; 95% CI, -4.2 to 1.90) or discharge GOS (adjusted difference, -0.67; 95% CI -1.9 to 0.63). Conclusions: This study suggests that compared with REBOA Zone 1, REBOA Zone 3 provides superior survival and is not inferior regarding other adverse outcomes in patients with severe blunt pelvic injuries.
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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.