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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Severe burn injuries induce acute and chronic susceptibility to infections, which is largely attributed to a hyper-proinflammatory response followed by a chronic anti-inflammatory response. Concurrent inhalation injury (B + I) causes airway inflammation. Pulmonary macrophages and neutrophils are "hyperactive" with increased reactive oxygen (ROS) and nitrogen species (RONS) activity, but are unable to clear infection, causing airway damage upon activation. ⋯ BI-injured mice that received Combo-MP an hour after injury, inoculated 48 h later with Pseudomonas aeruginosa (PAO1), and sacrificed 48 h after infection displayed significantly decreased bacterial counts in the lungs and liver versus untreated B + I mice. This reduction in infection was accompanied by significantly altered lung and plasma cytokine profiles and immune reprogramming of pulmonary and splenic cells. Our findings strongly suggest that multimodal MP-based therapy holds considerable promise for reprogramming the immune response after burn injuries, particularly by mitigating the hyper-inflammatory phase and preventing subsequent susceptibility to infection.
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Sepsis is a life-threatening condition driven by a dysregulated immune response to infection. Identifying the genetic factors underlying sepsis pathogenesis remains a major challenge in developing effective treatments. ⋯ BEND7 was identified as a platelet-specific gene involved in immune regulation during sepsis. Targeting BEND7-positive platelets may present new therapeutic opportunities in sepsis management.
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Background: Acute kidney injury (AKI) is a common complication of vasodilatory shock. AKI is associated with an increased risk of death, prolonged hospital stays, and subsequent transition to chronic kidney disease. Catecholamines have historically been used as the first-line vasopressors for vasodilatory shock; however, they may adversely affect renal function and recovery. ⋯ Conclusions: Preclinical and clinical studies suggest that non-catecholamine vasopressors may confer renal benefits compared to catecholamine vasopressors. These hypothesis-generating observations suggest the need for comparative studies focused on renal outcomes. Systematic Review Registration: PROSPERO 2024 CRD42024527773.