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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Thrombomodulin alfa (TM alfa) has been shown effective for treatment of disseminated intravascular coagulation (DIC) associated with sepsis, although the optimal therapeutic plasma concentration has not been clarified. In the present study, the plasma trough concentration of TM alfa in septic patients with DIC was determined, then the cutoff value for that concentration showing influence on treatment outcome was calculated using a receiver operating characteristic curve. With a cutoff value of 1,010, the area under the curve of the receiver operating characteristic was 0.669 (95% confidence interval, 0.530-0.808), with sensitivity of 0.458 and specificity of 0.882. ⋯ The above-cutoff group showed a significantly higher 90-day survival rate (91.7%) as compared with the below-cutoff group (63.4%) ( P = 0.017), with a hazard ratio of 0.199 (95% confidence interval, 0.045-0.871). Interestingly, the incidence of hemorrhagic adverse effects was not significantly different between the groups. Based on these results, the recommended plasma trough concentration of TM alfa for treatment of septic DIC is 1,010 ng/mL, which should minimize the risk of severe bleeding while maximizing the therapeutic effect.
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Study hypothesis : Implementation of a new pathway dedicated to septic patients within the emergency department (ED) would improve early management, organ dysfunction, and outcome. Methods: During phase 1, all consecutive adult patients with infection and qualifying quick Sequential Organ Failure Assessment (qSOFA) score upon ED admission were managed according to standards of care. A multifaceted intervention was then performed (implementation phase): educational program, creation of a sepsis alert upon ED admission incorporated in the professional software, together with severity scores and Surviving Sepsis Campaign (SSC) bundle reminders, and dedication of two rooms to the management of septic patients (sepsis unit). ⋯ Mortality significantly decreased during the second phase, on day 3 (28% vs. 15%, P = 0.008) and on day 28 (40% vs. 28%, P = 0.013). Conclusion: Systematic detection, education, and per protocol organization with a sepsis unit dedicated to the early management of septic patients appear to improve compliance with SSC bundles, organ dysfunction, and short-term mortality. These results warrant to be confirmed by prospective studies.
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Several studies have demonstrated the clinical utility of tranexamic acid (TXA) for use in trauma patients presenting with significant hemorrhage. Tranexamic acid is an antifibrinolytic that inhibits plasminogen activation, and plasmin activity has been shown to mitigate blood loss and reduce all-cause mortality in the absence of adverse vascular occlusive events. Recent clinical developments indicate TXA is safe to use in patients with concomitant traumatic brain injury (TBI); however, the prehospital effects are not well understood. ⋯ We observed no exacerbation of cerebral thrombosis, but TXA treatment caused an increased risk of EEG abnormalities. These results suggest that TXA following polytrauma with concomitant brain injury may provide mild neuroprotective effects by preventing lesion progression, but this may be associated with an increased risk of abnormal EEG patterns. This risk may be associated with TXA inhibition of glycine receptors and may warrant additional considerations during the use of TXA in patients with severe TBI.
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Background: Circular RNAs (circRNAs) have been shown to mediate atherosclerosis (AS) process by regulating vascular smooth muscle cells (VSMCs) function. However, whether circ_0091822 mediates VSMCs function to regulate AS process is unclear. Methods: Oxidized low-density lipoprotein (ox-LDL) was used to treat VSMCs for constructing AS cell models. ⋯ MiR-339-5p targeted BOP1, and BOP1 also reversed the repressing effect of miR-339-5p on ox-LDL-induced VSMCs functions. Circ_0091822/miR-339-5p/BOP1 axis promoted the activity of Wnt/β-catenin pathway. Conclusions: Circ_0091822 might be a therapeutic target for AS, which facilitated ox-LDL-induced VSMCs proliferation, invasion, and migration through modulating miR-339-5p/BOP1/Wnt/β-catenin pathway.
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Background: Hemorrhage remains the leading cause of death on the battlefield. This study aims to assess the ability of an artificial intelligence triage algorithm to automatically analyze vital-sign data and stratify hemorrhage risk in trauma patients. Methods: Here, we developed the APPRAISE-Hemorrhage Risk Index (HRI) algorithm, which uses three routinely measured vital signs (heart rate and diastolic and systolic blood pressures) to identify trauma patients at greatest risk of hemorrhage. ⋯ The APPRAISE-HRI stratification yielded a hemorrhage likelihood ratio (95% confidence interval) of 0.28 (0.13-0.43) for HRI:I, 1.00 (0.85-1.15) for HRI:II, and 5.75 (3.57-7.93) for HRI:III, suggesting that patients categorized in the low-risk (high-risk) category were at least 3-fold less (more) likely to have hemorrhage than those in the average trauma population. We obtained similar results in a cross-validation analysis. Conclusions: The APPRAISE-HRI algorithm provides a new capability to evaluate routine vital signs and alert medics to specific casualties who have the highest risk of hemorrhage, to optimize decision-making for triage, treatment, and evacuation.