Platelets have received increasing attention for their role in the pathophysiology of infectious disease, inflammation, and immunity. In sepsis, a low platelet count is a well-known biomarker for disease severity and more recently authors have focused their attention on the active role of platelets in the pathogenesis of multi-organ failure. Septic shock is characterised by a dysregulated inflammatory response, which can impair the microcirculation and lead to organ injury. Being at the crossroads between the immune system, clotting cascade, and endothelial cells, platelets seem to be an appealing central mediator and possible therapeutic target in sepsis. This review focuses on the pathogenic role of platelets in septic organ dysfunction in humans and animal models.

Objective: To explain the paradigm of significant renal functional impairment despite preserved hemodynamics and histology in sepsis-induced acute kidney injury. Design: Prospective observational animal study. Setting: University research laboratory. Subjects: Male Wistar rats. Intervention: Using a fluid-resuscitated sublethal rat model of fecal peritonitis, changes in renal function were characterized in relation to global and renal hemodynamics, and histology at 6 and 24 hours (n = 6–10). Sham-operated animals were used as comparison (n = 8). Tubular cell mitochondrial function was assessed using multiphoton confocal imaging of live kidney slices incubated in septic serum. Measurements and Main Results: By 24 hours, serum creatinine was significantly elevated with a concurrent decrease in renal lactate clearance in septic animals compared with sham-operated and 6-hour septic animals. Renal uncoupling protein-2 was elevated in septic animals at 24 hours although tubular cell injury was minimal and mitochondrial ultrastructure in renal proximal tubular cells preserved. There was no significant change in global or renal hemodynamics and oxygen delivery/consumption between sham-operated and septic animals at both 6- and 24-hour timepoints. In the live kidney slice model, mitochondrial dysfunction was seen in proximal tubular epithelial cells incubated with septic serum with increased production of reactive oxygen species, and decreases in nicotinamide adenine dinucleotide and mitochondrial membrane potential. These effects were prevented by coincubation with the reactive oxygen species scavenger, 4-hydroxy-2,2,6,6-tetramethyl-piperidin-1-oxyl. Conclusions: Renal dysfunction in sepsis occurs independently of hemodynamic instability or structural damage. Mitochondrial dysfunction mediated by circulating mediators that induce local oxidative stress may represent an important pathophysiologic mechanism.

Severe COVID-19 and bacterial sepsis share clinical manifestations of systemic inflammation and organ dysfunction. Yet, early differentiation between these conditions and timely identification of patients at risk of deterioration remain major clinical challenges. Extracellular vesicle (EV)-associated microRNAs (miRNAs) have emerged as promising biomarkers of host immune dysregulation. In our study, we have characterized circulating EV-miRNAs in patients with COVID-19, bacterial sepsis, localized bacterial infections, and healthy subjects to assess their diagnostic and prognostic utility. After EV isolation from plasma and characterization by nanoparticle tracking analysis and flow cytometry, a panel of 12 inflammation-related miRNAs were individually quantified by qRT-PCR. Four EV-miRNAs—miR-28-5p, miR-199a-5p, miR-200a-3p, and miR-369-3p—were significantly elevated in COVID-19 patients, with higher levels in those with poor prognosis. miR-199a-5p and miR-200a-3p were increased in bacterial sepsis compared with COVID-19, enabling discrimination between viral and bacterial sepsis. Three EV-miRNAs—miR-28-5p, miR-199a-5p, and miR-200a-3p—were markedly higher in bacterial sepsis than localized infections, and ROC analysis showed a strong diagnostic performance, particularly for miR-199a-5p, alone or in combination with other EV-miRNAs. The increased expression of selected EV-miRNAs was associated with higher SOFA scores and in-hospital mortality. These findings indicate that EV-miRNAs reflect pathogen-specific and severity-related immune responses, supporting their potential as minimally invasive biomarkers for early diagnosis and risk stratification in severe infections.

Article: Incidence and management of agitation during non-invasive mechanical ventilation outside intensive care units: an observational cohort study in a high dependency unit - Panminerva Medica 2023 Sep 21 - Minerva Medica - Journals