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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Objectives: Nosocomial pneumonia is a common complication in critically ill patients. The goal of this study was to examine the efficacy of the Toll-like receptor 4 agonist 3-deacyl phosphorylated hexacyl disaccharide (3D PHAD), in a clinically relevant murine model of pneumonia, and assess the cellular mechanisms that mediate the protective response. Design: Mice received intrapulmonary 3D PHAD (20 μg) or vehicle for 2 consecutive days before challenge with intrapulmonary Klebsiella pneumoniae (2.3 × 10 3 colony-forming units). ⋯ Lung innate leukocytes from 3D PHAD-treated mice had increased phagocytic capacity. Treatment with 3D PHAD alone increased cytokines in the lungs but decreased cytokines in plasma during K. pneumoniae pneumonia as compared with control. Conclusions: Intrapulmonary treatment with 3D PHAD augments innate immunity in the lung and facilitates resistance to K. pneumoniae pneumonia.
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Observational Study
Diagnostic accuracy and added value of infection biomarkers in patients with possible sepsis in the Emergency Department.
Background: Biomarkers for early recognition of infection are warranted. The hypothesis of this study was that calprotectin, C-reactive protein (CRP), IL-6 and procalcitonin (PCT), alone or in combination, provide clinically useful information to the clinicians for early identification of infection in patients with possible sepsis in the emergency department (ED). Biomarker dynamics in the first week of hospitalization were explored. ⋯ Longitudinal samples revealed that IL-6 peaked in the ED, whereas CRP and PCT peaked later. Conclusion: C-reactive protein and IL-6 were superior to calprotectin and PCT for recognizing infection in patients with possible sepsis in the ED. Combining these two biomarkers with different dynamics improved recognition of infection and could aid clinical management in rapid response teams in the ED.
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Objective: To examine the risk factors, resource utilization, and 1-year mortality associated with vasopressor-resistant hypotension (VRH) compared with vasopressor-sensitive hypotension (VSH) among critically ill adults with vasodilatory shock. We also examined whether combination vasopressor therapy and patient phenotype were associated with mortality. Design: Retrospective cohort study. ⋯ Conclusions: Among critically ill patients with vasodilatory shock, VRH compared with VSH is associated with increased resource utilization and long-term risk of death. However, combination vasopressor therapy was not associated with lower risk of death. We identified four unique phenotypes of patient clusters that require further validation.
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Background: Traumatic brain injury (TBI) is an underrecognized public health threat. The constitutive activation of microglia after TBI has been linked to long-term neurocognitive deficits and the progression of neurodegenerative disease. Evolving evidence indicates a critical role for the gut-brain axis in this process. ⋯ Our data demonstrated significant preservation of cortical volume and white matter connectivity after an injury compared with mice treated with vehicle alone. This preservation of neuroanatomy after TBI was associated with a marked reduction in inflammatory gene expression within the microglia of FMT-treated mice. Microglia from FMT-treated mice enriched pathways in the heat-shock response, which is known to play a neuroprotective role in TBI and other neurodegenerative disease processes.
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We hypothesized that circulatory and jejunal mucosal blood flow would improve after 2-methyl-2thiazoline (2MT) administration in endotoxic shock. This study aimed to evaluate changes in systemic circulation and in superior mesenteric venous (SMV) blood flow and jejunal mucosal tissue blood flow of the intestinal vascular system over time after administration of 2MT in rabbits with endotoxic shock. We created four groups (n = 6 each): control group, LPS (1 mg/kg) group, 2MT (80 mg/kg) group, and LPS-2MT group. ⋯ An interaction between 2MT and LPS was observed for jejunal mucosal tissue blood flow from 90 to 180 min and at 240 min (P < 0.05). We showed that 2MT maintained MAP and improved SMV blood flow and jejunal mucosal tissue blood flow. In a rabbit model of endotoxic shock, 2MT had a positive effect on MAP and jejunal mucosal tissue blood flow.