Articles: sepsis.
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Randomized Controlled Trial
Glucocorticoid treatment increases cholesterol availability during critical illness: effect on adrenal and muscle function.
Hypocholesterolemia hallmarks critical illness though the underlying pathophysiology is incompletely understood. As low circulating cholesterol levels could partly be due to an increased conversion to cortisol/corticosterone, we hypothesized that glucocorticoid treatment, via reduced de novo adrenal cortisol/corticosterone synthesis, might improve cholesterol availability and as such affect adrenal gland and skeletal muscle function. ⋯ Glucocorticoid treatment partially attenuated critical illness-induced hypocholesterolemia, but at a cost of impaired adrenal function, suppressed muscle regeneration and exacerbated loss of body mass.
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Mechanical ventilation (MV) is a clinically important measure for respiratory support in critically ill patients. Although moderate tidal volume MV does not cause lung injury, it can further exacerbate lung injury in pathological state such as sepsis. This pathological process is known as the 'two-hit' theory, whereby an initial lung injury (e.g., infection, trauma, or sepsis) triggers an inflammatory response that activates immune cells, presenting the lung tissue in a fragile state and rendering it more susceptible to subsequent injury. The second hit occurs when mechanical ventilation is applied to lung tissue in a fragile state, and it is noteworthy that this mechanical ventilation is harmless to healthy lung tissue, further aggravating pre-existing lung injury through unknown mechanisms. This interaction between initial injury and subsequent mechanical ventilation develops a malignant cycle significantly exacerbating lung injury and severely hampering patient prognosis. The two-hit theory is critical to understanding the complicated mechanisms of ventilator-associated lung injury and facilitates the subsequent development of targeted therapeutic strategies. ⋯ These data show for the first time that the Caspase-1/Caspase-11-HMGB1-TLR4/RAGE signaling pathway plays a key role in mice model of sepsis induced lung injury exacerbated by MV. Different species of HMGB1 knockout mice have different lung protective mechanisms in the 'two hits' model, and location is the key to function. Specifically, LysM HMGB1-/- mice due to the deletion of HMGB1 in myeloid cells resulted in a pulmonary protective mechanism that was associated with a downregulation of the inflammatory response. EC HMGB1-/- mice are deficient in HMGB1 owing to endothelial cells, resulting in a distinct pulmonary protective mechanism independent of the inflammatory response and more relevant to the improvement of alveolar-capillary permeability. iHMGB1-/- mice, which are systemically HMGB1-deficient, share both of these lung-protective mechanisms.
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Meta Analysis
Divergent effects of tumor necrosis factor (TNF) in sepsis: a meta-analysis of experimental studies.
Experimental studies in animals have yielded conflicting results on the role of Tumor Necrosis Factor (TNF) in sepsis and endotoxemia, with some reporting adaptive and others inappropriate effects. A meta-analysis of the available literature was performed to determine the factors explaining this discrepancy. ⋯ The role of TNF during infection varies depending on the experimental model used. Models that mimic clinical conditions, based on virulent bacteria that cause high mortality even at low inocula, demonstrated an adaptive role of TNF. Conversely, models based on LPS or low-pathogenic live bacteria, administered at doses well above physiological thresholds and combined with early antibiotic therapy, were associated with an inappropriate role.
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Retained placenta can lead to septic shock; however, sepsis-induced cardiomyopathy (SICM) due to retained placenta has not been reported previously. This report presents a rare case of SICM following septic shock due to retained placenta after miscarriage in a 40-year-old woman, accompanied by the "shark fin sign" on an electrocardiogram, a pattern typically linked to myocardial ischemia. ⋯ We also reviewed previous cases of shark fin sign in patients without myocardial infarction. A review showed that half of the cases experienced lethal arrhythmias, even without myocardial infarction.
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Sepsis is a heterogeneous syndrome. This study aimed to identify new sepsis sub-phenotypes using plasma cortisol trajectory. ⋯ This study identified two novel cortisol trajectory sub-phenotypes in patients with sepsis. The trajectories were associated with mortality, providing new insights into sepsis classification.