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Endothelial glycocalyx (EG) shedding is associated with septic shock and described following intravenous (IV) fluid administration. To investigate the possible impact of IV fluids on the pathobiology of septic shock we investigated associations between biomarkers of EG shedding and endothelial cell activation, and relationships with IV fluid volume. Serum samples were obtained on admission (T0) and at 24 h (T24) in patients undergoing haemodynamic resuscitation for suspected septic shock in the emergency department. Biomarkers of EG shedding-Syndecan-1 (Syn-1), Syndecan-4 (Syn-4), Hyaluronan, endothelial activation-Endothelin-1 (ET-1), Angiopoeitin-2 (Ang-2), Vascular Endothelial Growth Factor Receptor-1(VEGF-1) and leucocyte activation/inflammation-Resistin, Neutrophil Gelatinase Associated Lipocalin (NGAL) and a marker of cardiac stretch-Pro-Atrial Natriuretic Peptide (Pro-ANP) were compared to the total IV fluid volume administered using Tobit regression. Data on 86 patients (52 male) with a mean age of 60 (SD 18) years were included. The mean fluid volume administered to T24 was 4038 ml (SD 2507 ml). No significant association between fluid volume and Pro-ANP or any of the biomarkers were observed. Syn-1 and Syn-4 were significantly correlated with each other (Spearman Rho 0.43, p < 0.001) but not with Hyaluronan. Syn-1 and Syn-4 both correlated with VEGFR-1 (Rho 0.56 and 0.57 respectively, p < 0.001) whereas Hyaluronan correlated with ET-1 (Rho 0.43, p < 0.001) and Ang-2 (Rho 0.43, p < 0.001). There was no correlation between Pro-ANP and any of the EG biomarkers. Distinct patterns of association between biomarkers of EG shedding and endothelial cell activation were observed among patients undergoing resuscitation for sepsis. No relationship between IV fluid volume and Pro-ANP or any of the other biomarkers was observed., (© 2022. The Author(s).)

Objective and Design: Hypertonic saline administered during fluid resuscitation may mitigate endothelial glycocalyx (EG) shedding and inflammation. The objective of this pilot randomised controlled trial was to measure the effect of hypertonic saline, compared to isotonic saline, on biomarkers of EG shedding and inflammation in emergency department patients with suspected sepsis., Methods: Patients received either 5 mL/kg of 3% saline (hypertonic group, n = 34) or 10 mL/kg of 0.9% saline (isotonic group, n = 31). Change in serum biomarker concentrations of syndecan-1, hyaluronan, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, interleukin-6, -8, -10, interferon-γ, neutrophil gelatinase-associated lipocalin and resistin were compared from baseline (T0) to after fluid (T1), 3 h (T3) and 12-24 h (T24) later, as was serum osmolality, using linear mixed effects models., Results: The hypertonic group had significantly increased mean serum osmolality compared to the isotonic group at T1 (P < .001) and T3 (P = .004). Minor differences were found in some biomarker outcomes, including a decreased fold-change in syndecan-1 at T1 (P = .012) and in interleukin-10 at T24 (P = .006) in the isotonic group, compared to the hypertonic group., Conclusions: Although a single bolus of hypertonic saline increased serum osmolality, it did not reduce biomarkers of EG shedding or inflammation, compared to patients that received isotonic saline., Trial Registration: ANZCTR.org.au, ACTRN12611001021965, Registered on 23rd September 2011., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Endocan, a component of the endothelial glycocalyx (EG), has been linked with respiratory failure in sepsis. This study explored the temporal patterns of three EG biomarkers, including endocan, and their relationships with inflammation and respiratory failure., Materials and Methods: Plasma endocan, syndecan-1, and hyaluronan concentrations were measured in Emergency Department (ED) patients with sepsis due to pneumonia (n = 44) on ED arrival (T0), 1 h (T1), 3 h (T3) and 12-24 h (T24) later, with change over time tested using mixed regression models. Biomarker associations with inflammatory cytokine concentrations and with respiratory failure on days 1, 2 or 3, need for mechanical ventilation and 30-day mortality were also tested., Results: Endocan concentration significantly decreased over time (T0-T24, P = 0.003) whereas both syndecan-1 (T0-T3, P = 0.010; T0-T24, P < 0.001) and hyaluronan (T0-T1, P = 0.010; T0-T3, P < 0.001; T0-T24, P = 0.003) significantly increased over time. Increased syndecan-1 was significantly correlated with neutrophil activation biomarkers and significantly increased the odds of respiratory failure (OR 1.18, 95% CI 1.05-1.33, P = 0.004), need for mechanical ventilation (OR 1.24, 95% CI 1.04-1.48, P = 0.014) and 30-day mortality (OR 1.29, 95% CI 1.07-1.55, P = 0.008)., Conclusion: Syndecan-1, but not endocan, was associated with neutrophil activation and was the best EG biomarker predictor of adverse clinical outcomes., (Copyright © 2018. Published by Elsevier Inc.)

Purpose: Endothelial glycocalyx (EG) shedding may promote organ failure in sepsis. This study describes temporal changes in EG biomarkers from Emergency Department (ED) arrival, and associations with clinical characteristics., Materials and Methods: This prospective observational study included 23 patients with simple infection, 86 with sepsis and 29 healthy controls. Serum EG biomarkers included syndecan-1, syndecan-4 and hyaluronan. Samples were taken on enrolment in the ED (T0), 1 hour (T1), 3 hours (T3) and 12 to 24 hours (T24) later., Results: Syndecan-1 concentration increased incrementally over time (T0-T24, both patient groups, P < .001) whereas hyaluronan concentration peaked at T3 (T0-T3, sepsis group, P < .001). Hyaluronan was positively associated with cumulative fluid volumes (P < .001) at T0, T1, and T3, independent of illness severity. Both syndecan-1 (OR 1.04, 95% CI 1.01-1.07, P = .017) and hyaluronan (OR 1.83, 95% CI 1.46-2.30, P < .001) were associated with organ failure, independent of age and comorbidity. Syndecan-4 concentration was not different between groups or over time., Conclusions: In contrast to previous ICU studies, EG biomarkers increased during the first 24 hours of sepsis treatment and were associated with fluid volumes and organ failure. Further investigation is required to determine if interventions delivered in the ED contribute to EG shedding., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective and Design: Resistin and neutrophil gelatinase-associated lipocalin (NGAL) are upregulated in circulating leucocytes in sepsis, but the significance of this is uncertain. We evaluated associations between Resistin and NGAL with endothelial cell activation and clinical outcomes in a prospective observational study in the Emergency Department (ED)., Methods: Serum levels of Resistin, NGAL, inflammatory cytokines (IL-6, IL-10) and soluble endothelial adhesion molecules (VCAM-1, ICAM-1) were measured at defined time points up to 24 h. Patterns and relationships between markers were investigated using linear mixed regression models. Predictive values for clinical outcomes for markers at enrollment were assessed by logistic regression and receiver operator characteristic (ROC) curves., Results: 186 participants (89 septic-shock, 69 sepsis, 28 uncomplicated infection) were compared with 29 healthy controls. Median Resistin and NGAL were higher in uncomplicated infection compared to controls, and in septic shock compared to non-shock sepsis. Resistin and NGAL correlated with IL-6 and IL-10, with VCAM-1 and ICAM-1, and with organ failure. Resistin and NGAL were associated with septic shock but had limited predictive utility for mortality., Conclusion: Resistin and NGAL correlate with expression of endothelial cell adhesion molecules in sepsis. Further evaluation of the role of Resistin and NGAL in sepsis pathogenesis is warranted.

Objective: Mechanisms underlying the anaphylactic reaction in humans are not fully understood. Here, we aimed at improving our understanding of anaphylaxis by investigating gene expression changes. Methods: Microarray data set GSE69063 was analysed, describing emergency department (ED) patients with severe anaphylaxis (n = 12), moderate anaphylaxis (n = 6), sepsis (n = 20) and trauma (n = 11). Samples were taken at ED presentation (T0) and 1 h later (T1). Healthy controls were age and sex matched to ED patient groups. Gene expression changes were determined using limma, and pathway analysis applied. Differentially expressed genes were validated in an independent cohort of anaphylaxis patients (n = 31) and matched healthy controls (n = 10), using quantitative reverse transcription‐polymerase chain reaction. Results: Platelet aggregation was dysregulated in severe anaphylaxis at T0, but not in moderate anaphylaxis, sepsis or trauma. Dysregulation was not observed in patients who received adrenaline before T0. Seven genes (GATA1 (adjusted P‐value = 5.57 × 10−4), TLN1 (adjusted P‐value = 9.40 × 10−4), GP1BA (adjusted P‐value = 2.15 × 10−2), SELP (adjusted P‐value = 2.29 × 10−2), MPL (adjusted P‐value = 1.20 × 10−2), F13A1 (adjusted P‐value = 1.39 × 10−2) and SPARC (adjusted P‐value = 4.06 × 10−2)) were significantly downregulated in severe anaphylaxis patients who did not receive adrenaline before ED arrival, compared with healthy controls. One gene (TLN1 (adjusted P‐value = 1.29 × 10−2)) was significantly downregulated in moderate anaphylaxis patients who did not receive adrenaline before ED arrival, compared with healthy controls. Conclusion: Downregulation of genes involved in platelet aggregation and activation is a unique feature of the early anaphylactic reaction not previously reported and may be associated with reaction severity. [ABSTRACT FROM AUTHOR]

Background: Anaphylaxis is a severe, potentially life‐threatening allergic reaction driven primarily by the activation of mast cells. We still fail to understand factors underlying reaction severity. Furthermore, there is currently no reliable diagnostic test to confirm anaphylaxis in the emergency department (ED). Objective: This study sought to explore gene expression changes associated with anaphylaxis severity in peripheral blood leucocytes and evaluate biomarker potential. Methods: Microarray analysis (total RNA) was performed using peripheral blood samples from ED patients with moderate (n = 6) or severe (n = 12) anaphylaxis and sepsis (n = 20) at presentation (T0) and one hour later (T1). Results were compared between groups and healthy controls (n = 10 and n = 11 matched to anaphylaxis and sepsis patients, respectively). Changes in gene expression were determined using R programming language, and pathway analysis applied to explore biological processes and pathways associated with genes. Differentially expressed genes were validated in an independent cohort of anaphylaxis (n = 30) and sepsis (n = 20) patients, and healthy controls (n = 10), using quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR). Results: Significant up‐regulation of small nucleolar RNAs (snoRNAs) was demonstrated in anaphylaxis compared to sepsis patients in the microarray cohort, at T0 and T1. qRT‐PCR analysis of the validation cohort showed five genes: SNORD61, SNORD8, SNORD69, SNORD119 and HIST1H1D to be significantly up‐regulated (adjusted p < 0.05) in severe anaphylaxis compared to sepsis. Seven genes (SNORD61, SNORD8, SCARNA21, SNORD69, SNORD110, SNORD119 and SNORD59A) were significantly up‐regulated (adjusted p < 0.05) in severe anaphylaxis compared to healthy controls. Conclusion: This study demonstrates for the first time the unique involvement of snoRNAs in the pathogenesis of anaphylaxis and suggests they are not a general feature of systemic inflammation. Further investigation of snoRNA expression in anaphylaxis could provide insights into disease pathogenesis. Clinical relevance: SnoRNAs are up‐regulated during acute anaphylaxis in humans and could potentially be used as biomarkers of severe anaphylaxis. [ABSTRACT FROM AUTHOR]