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Sepsis is a severe disease characterized by an uncontrolled systemic inflammation and consequent organ dysfunction generated in response to an infection. Extracellular ATP acting through the P2X7 receptor induces the maturation and release of pro-inflammatory cytokines (i.e., IL-1β) and the production of reactive nitrogen and oxygen species that lead to oxidative tissue damage. Here, we investigated the role of the P2X7 receptor in inflammation, oxidative stress, and liver injury in sepsis. Sepsis was induced by cecal ligation and puncture (CLP) in wild-type (WT) and P2X7 knockout (P2X7 -/- ) mice. The oxidative stress in the liver of septic mice was assessed by 2',7'-dichlorofluorescein oxidation reaction (DCF), thiobarbituric acid-reactive substances (TBARS), and nitrite levels dosage. The status of the endogenous defense system was evaluated through catalase (CAT) and superoxide dismutase (SOD) activities. The inflammation was assessed histologically and by determining the expression of inflammatory cytokines and chemokines by RT-qPCR. We observed an increase in the reactive species and lipid peroxidation in the liver of septic WT mice, but not in the liver from P2X7 -/- animals. We found an imbalance SOD/CAT ratio, also only WT septic animals. The number of inflammatory cells and the gene expression of IL-1 β, IL-6, TNF-α, IL-10, CXCL1, and CXCL2 were higher in the liver of WT septic mice in comparison to P2X7 -/- septic animals. In summary, our results suggest that the P2X7 receptor might be a therapeutic target to limit oxidative stress damage and liver injury during sepsis.

Herein, we report the effect of gold nanoparticles (AuNP) and n-acetylcysteine (NAC) isolated or in association as important anti-inflammatory and antioxidant compounds on brain dysfunction in septic rats. Male Wistar rats after sham operation or caecal ligation and perforation (CLP) were treated with subcutaneously injection of AuNP (50 mg/kg) and/or NAC (20 mg/kg) or saline immediately and 12 h after surgery. Twenty-four hours after CLP, hippocampus and prefrontal cortex were obtained and assayed for myeloperoxidase (MPO) activity, cytokines, lipid peroxidation, protein carbonyls formation, mitochondrial respiratory chain, and CK activity. AuNP + NAC association decreased MPO activity and pro-inflammatory cytokines production, being more effective than NAC or AuNP isolated treatment. AuNP + NAC association and NAC isolated treatment decreased oxidative stress to lipids in both brain structures, while protein oxidation decreased only in the hippocampus of AuNP + NAC association-treated animals. Complex I activity was increased with AuNP + NAC association and NAC isolated in the hippocampus. Regarding CK activity, AuNP and AuNP + NAC association increased this marker in both brain structures after CLP. Our data provide the first experimental demonstration that AuNP and NAC association was able to reduce sepsis-induced brain dysfunction in rats by decreasing neuroinflammation, oxidative stress parameters, mitochondrial dysfunction and CK activity.

Purpose: Lung ultrasound is an accurate and accessible tool to quantify lung edema. Furthermore, left ventricle filling pressures (LVFP) can be assessed with transthoracic echocardiography (TTE) by the E/e' ratio (E/e'). The present study aimed to assess the correlation between E/e' and lung edema quantified by a simplified lung ultrasound score (LUS) in newly admitted septic patients., Materials and Methods: In this prospective observational cohort, septic adult patients admitted at the emergency department of a tertiary hospital were included. LUS consisted of four different patterns of lung edema (from normal aeration to parenchymal consolidation). To compare lung edema with LVFP, E/e' was calculated immediately before or within 5min of fluid therapy., Results: Fifty patients were enrolled in 3months. The LUS correlated with E/e' (r=0.58, P<0.0001). The LUS also increased among E/e' quartiles (Q) (Q1: E/e'≤4.49; Q2: 4.497.11; P=0.0003 for Q1 and 4; 2 and 4); and LUS was significantly higher in abnormal (≥8) vs. normal (<8) values of E/e' (11.29 vs 8.49, P=0.007)., Conclusion: In newly admitted septic patients, lung edema is positively correlated with LVFP prior to fluid therapy. This finding might help find future targets for fluid resuscitation in sepsis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Endothelial barrier dysfunction is a hallmark of sepsis, and is at least partially mediated by pathways that regulate endothelial barrier assembly during angiogenesis. Not surprisingly, increased levels of key angiogenic proteins such as VEGF-A and Angiopoietin-2 have been described in sepsis. The purpose of this study was to investigate if additional pathways that regulate endothelial barrier integrity during angiogenesis could also be involved in the host response of sepsis., Material and Methods: We evaluated circulating levels of four proteins involved in angiogenesis, not previously studied in sepsis, in a cohort of 50 patients with severe sepsis and septic shock., Results: Circulating levels of BMP-9 and FGF-2 were similar in patients and healthy volunteers. In contrast, patients with septic shock presented 1.5-fold higher levels of endoglin (P=0.004), and 2-fold lower levels of Heparin-Binding EGF-like growth factor (HB-EGF) (P=0.002) when compared to healthy individuals. Of note, HB-EGF deficiency has been recently demonstrated to be detrimental to survival in a murine model of sepsis., Conclusions: Endoglin and HB-EGF could be involved in the host response of sepsis. Additional studies are warrant to investigate their role as biomarker or therapeutic targets in sepsis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

We prospectively evaluated afebrile patients admitted to an emergency department (ED), with suspected infection and only tachycardia or tachypnea.The white blood cell count (WBC) was obtained, and patients were considered septic if leukocyte count was >12,000 μL-1 or <4000 μL-1 or with >10% of band forms. Clinical data were collected to examine whether sepsis could be predicted.Seventy patients were included and 37 (52.86%) met sepsis criteria. Self-measured fever showed an odds ratio (OR) of 5.936 (CI95% 1.450-24.295; P = 0.0133) and increased pulse pressure (PP) showed an OR of 1.405 (CI95% 1.004-1.964; P = 0.0471) on multivariate analysis. When vital signs were included in multivariate analysis, the heart rate showed an OR of 2.112 (CI95% 1.400-3.188; P = 0.0004). Self-measured fever and mean arterial pressure <70 mm Hg had high positive likelihood ratios (3.86 and 2.08, respectively). The nomogram for self-measured fever showed an increase of sepsis chance from 53% (pretest) to approximately 80% (post-test).The recognition of self-measured fever, increased PP, and the intensity of heart rate response may improve sepsis recognition in afebrile patients with tachycardia or tachypnea. These results are important for medical assessment of sepsis in remote areas, crowded and low-resourced EDs, and low-income countries, where WBC may not be readily available.

Background: Assessment of sepsis severity is challenging. Available scoring systems require laboratory data. Therefore, a rapid tool would be useful., Objective: To determine the role of mitral valve tissue Doppler imaging (TDI) as a prognostic tool in septic patients., Methods: For this prospective cohort, newly admitted septic patients received TDI measurements of s wave (s), e' wave (e'), and E/e' ratio (E/e') within 5 min of resuscitation. Results were compared with sepsis severity measured by Mortality in Emergency Department Sepsis (MEDS), Simplified Acute Physiology Score (SAPS) 3, and Sequential Organ Failure Assessment (SOFA)., Results: Over 3 months, 63 patients were enrolled. TDI parameters correlated with MEDS, SAPS 3, and SOFA (r = -0.53, r = -0.55, r = -0.36, respectively, for s, p < 0.005; r = -0.56, r = -0.49, r = -0.40, respectively, for e', p < 0.005; and r = 0.56; r = 0.48; r = 0.46, respectively, for E/e', p < 0.005). Mean s and e' decreased among sepsis, severe sepsis, and septic shock patients (14.2; 12.05; 10.14 cm/s, respectively, for s, p = 0.0048 and 18.28; 15.14; 12.12 cm/s, respectively, for e', p = 0.003), whereas mean E/e' increased among sepsis stages (4.76; 6.51; and 8.14, respectively, p = 0.001). Mean s and e' were higher in survivors (13.25 vs. 7.33 cm/s, for s, p < 0.0001; and 16.4 vs. 9 cm/s for e', p = 0.0025); mean E/e' was higher in nonsurvivors (10.85 vs. 5.63, p < 0.0001). On univariate analysis, odds ratios (ORs) for death related to s, e', and E/e' were, respectively, 0.517 (95% confidence interval [CI] 0.344-0.775), 0.60 (95% CI 0.433-0.833), and 1.953 (95% CI 1.256-3.008); p < 0.05 for all. Multiple logistic analysis showed an OR of 1.737 (95% CI 1.037-2.907, p = 0.035) for death related to E/e'., Conclusion: TDI may be useful to assess disease severity and prognosis in newly diagnosed septic patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Management of Sepsis would greatly benefit from the incorporation of simple and informative new biomarkers in clinical practice. Ideally, a sepsis biomarker should segregate infected from non-infected patients, provide information about prognosis and organ-specific damage, and be accessible to most healthcare services. The immature platelet fraction (IPF) and immature reticulocyte fraction (IRF) are new analytical parameters of the complete blood count, that have been studied as biomarkers of several inflammatory conditions. Recently, a study performed in critically-ill patients suggested that IPF could be a more accurate sepsis biomarker than C-reactive protein (CRP) and procalcitonin. In this retrospective study we evaluated the performance of IPF and IRF as biomarkers of sepsis diagnosis and severity. 41 patients admitted to two intensive care units were evaluated, 12 of which with severe sepsis or septic shock, and 11 with non-complicated sepsis. Significantly higher IPF levels were observed in patients with severe sepsis/septic shock. IPF correlated with sepsis severity scores and presented the highest diagnostic accuracy for the presence of sepsis of all studied clinical and laboratory parameters. No significant differences were observed in IRF levels. Our results suggest that IPF levels could be used as a biomarker of sepsis diagnosis and severity.

Background: Lung ultrasound (US) is an excellent tool to assess lung edema in a myriad of different clinical situations. We hypothesized that lung US might also be a good prognostic and management instrument in septic patients, regardless of disease severity., Methods: This was a prospective observational cohort study at an urban academic emergency department (ED). Inclusion criteria were as follows: septic patients, at least 18 years old, admitted at the ED of a tertiary hospital. A simplified lung edema scoring system (SLESS) was developed, and 6 thoracic regions were evaluated. Four different lung US patterns were considered, from normal aeration to total consolidation. To evaluate disease severity, the SLESS was compared with the Mortality in Emergency Department Sepsis Score and the third version of the Simplified Acute Physiology Score scoring systems. Aiming to assess the effect of the lung edema in the gas exchange, the SLESS was compared with the Pao2/fraction of inspired oxygen ratio., Results: Sixty-one patients were enrolled in a 3-month period. The SLESS had a good correlation with the Mortality in Emergency Department Sepsis Score and Simplified Acute Physiology Score (r = 0.53 and r = 0.55, respectively; P < .001 for both) and a negative correlation with the Pao2/fraction of inspired oxygen ratio (r = -0.62; P < .001). The SLESS also showed correlation with the respiratory rate (r = 0.45; P = .0003). The odds ratio for death related to the SLESS was 1.370 (95% confidence interval, 1.109-1.691; P = .0035)., Conclusion: The SLESS is an easy and practical scoring system. It might be a useful tool to predict severity of disease in sepsis patients. The SLESS might also be able to be correlated with the oxygen exchange., (© 2013 Elsevier Inc. All rights reserved.)