Host derived biomarkers of inflammation, apoptosis, and endothelial activation are associated with clinical outcomes in patients with bacteremia and sepsis regardless of microbial etiology.
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ABSTRACT:
SUBMITTER: Hahn WO
PROVIDER: S-EPMC4871669 | biostudies-literature | 2016 May
REPOSITORIES: biostudies-literature
Publications
Host derived biomarkers of inflammation, apoptosis, and endothelial activation are associated with clinical outcomes in patients with bacteremia and sepsis regardless of microbial etiology.
Hahn William O WO Mikacenic Carmen C Price Brenda L BL Harju-Baker Susanna S Katz Ronit R Himmelfarb Jonathan J Wurfel Mark M MM Liles W Conrad WC
Virulence 20160128 4
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Project description:PurposeTo investigate the effect of IV fluid resuscitation on endothelial glycocalyx (EG) shedding and activation of the vascular endothelium and inflammation.Materials and methodsA planned biomarker sub-study of the REFRESH trial in which emergency department (ED) patients) with suspected sepsis and hypotension were randomised to a restricted fluid/early vasopressor regimen or IV fluid resuscitation with later vasopressors if required (usual care). Blood samples were collected at randomisation (T0) and at 3 h (T3), 6 h (T6)- and 24 h (T24) for measurement of a range of biomarkers if EG shedding, endothelial cell activation and inflammation.ResultsBlood samples were obtained in 95 of 99 enrolled patients (46 usual care, 49 restricted fluid). Differences in the change in biomarker over time between the groups were observed for Hyaluronan (2.2-fold from T3 to T24, p = 0.03), SYN-4 (1.5-fold from T3 to T24, P = 0.01) and IL-6 (2.5-fold from T0 to T3, p = 0.03). No difference over time was observed between groups for the other biomarkers.ConclusionsA consistent signal across a range of biomarkers of EG shedding or of endothelial activation or inflammation was not demonstrated. This could be explained by pre-existing EG shedding or overlap between the fluid volumes administered in the two groups in this clinical trial. Trial registration Australia New Zealand Clinical Trials Registry ACTRN126160000006448 Registered 12 January 2016.
| S-EPMC10106534 | biostudies-literature
Project description:ObjectiveThe purpose of this study was to identify a panel of biomarkers for distinguishing early stage sepsis patients from non-infected trauma patients.BackgroundAccurate differentiation between trauma-induced sterile inflammation and real infective sepsis poses a complex life-threatening medical challenge because of their common symptoms albeit diverging clinical implications, namely different therapies. The timely and accurate identification of sepsis in trauma patients is therefore vital to ensure prompt and tailored medical interventions (provision of adequate antimicrobial agents and if possible eradication of infective foci) that can ultimately lead to improved therapeutic management and patient outcome. The adequate withholding of antimicrobials in trauma patients without sepsis is also important in aspects of both patient and environmental perspective.MethodsIn this proof-of-concept study, we employed advanced technologies, including Matrix-Assisted Laser Desorption/Ionization (MALDI) and multiplex antibody arrays (MAA) to identify a panel of biomarkers distinguishing actual sepsis from trauma-induced sterile inflammation.ResultsBy comparing patient groups (controls, infected and non-infected trauma and septic shock patients under mechanical ventilation) at different time points, we uncovered distinct protein patterns associated with early trauma-induced sterile inflammation on the one hand and sepsis on the other hand. SYT13 and IL1F10 emerged as potential early sepsis biomarkers, while reduced levels of A2M were indicative of both trauma-induced inflammation and sepsis conditions. Additionally, higher levels of TREM1 were associated at a later stage in trauma patients. Furthermore, enrichment analyses revealed differences in the inflammatory response between trauma-induced inflammation and sepsis, with proteins related to complement and coagulation cascades being elevated whereas proteins relevant to focal adhesion were diminished in sepsis.ConclusionsOur findings, therefore, suggest that a combination of biomarkers is needed for the development of novel diagnostic approaches deciphering trauma-induced sterile inflammation from actual infective sepsis.
| S-EPMC10820703 | biostudies-literature
Project description:Background: Adult hemophagocytic lymphohistiocytosis (HLH) is highly lethal in the ICU. The diagnostic and therapeutic emergency that HLH represents is compounded by its unknown pathophysiological mechanisms. Here, we report on a large cohort of adult HLH in the ICU (ICU-HLH). We analyzed prognostic factors associated with mortality to define the diagnostic and therapeutic challenges in this specific population. Methods: This retrospective study included adult patients diagnosed with HLH in four ICUs in Marseille, France between 2010 and 2020. Patients who fulfilled the HLH-2004 criteria (≥ 4/8) and/or had an HScore ≥ 169 were diagnosed with HLH. HLH was categorized into four groups according to etiology: sepsis-associated HLH, intracellular infection-associated HLH, malignancy-associated HLH, and idiopathic HLH. Results: Two hundred and sixty patients were included: 121 sepsis-associated HLH (47%), 84 intracellular infection-associated HLH (32%), 28 malignancy-associated HLH (11%), and 27 idiopathic HLH (10%). The ICU mortality rate reached 57% (n = 147/260) without a statistical difference between etiological groups. Independent factors associated with mortality in multivariate analysis included age (OR (5 years) = 1.31 [1.16-1.48], p < 0.0001), SOFA score at ICU admission (OR = 1.37 [1.21-1.56], p < 0.0001), degradation of the SOFA score between ICU arrival and HLH diagnosis (Delta SOFA) (OR = 1.47 [1.28-1.70], p < 0.0001), the presence of bone-marrow hemophagocytosis (OR = 5.27 [1.11-24.97], p = 0.04), highly severe anemia (OR = 1.44 [1.09-1.91], p = 0.01), and hypofibrinogenemia (OR = 1.21 [1.04-1.41], p = 0.02). Conclusions: In this large retrospective cohort study of critically ill patients, ICU-HLH in adults was associated with a 57% mortality rate, regardless of HLH etiology or specific treatment. Factors independently associated with prognosis included age, presence of hemophagocytosis in bone-marrow aspirates, organ failure at admission, and worsening organ failure during the ICU stay. Whether a rapid diagnosis and the efficacy of specific therapy improve outcome is yet to be prospectively investigated.
| S-EPMC8526960 | biostudies-literature
Project description: Not available
| S-EPMC7901591 | biostudies-literature
Project description:Diagnosing pneumonia and identifying those requiring antibiotherapy remain challenging. Chest radiographs (CXR) are often used as the reference standard. We aimed to describe clinical characteristics, host-response biomarkers and etiology, and assess their relationship to CXR findings in children with pneumonia in Thimphu, Bhutan. Children between 2 and 59 months hospitalized with WHO-defined pneumonia were prospectively enrolled and classified into radiological endpoint and non-endpoint pneumonia. Blood and nasopharyngeal washing were collected for microbiological analyses and plasma levels of 11 host-response biomarkers were measured. Among 149 children with readable CXR, 39 (26.2%) presented with endpoint pneumonia. Identification of respiratory viruses was common, with no significant differences by radiological outcomes. No clinical sign was suggestive of radiological pneumonia, but children with radiological pneumonia presented higher erythrocyte sedimentation rate, C-reactive protein and procalcitonin. Markers of endothelial and immune activation had little accuracy for the reliable identification of radiological pneumonia.
| S-EPMC8891828 | biostudies-literature
Project description:IntroductionA strong biologic rationale exists for targeting markers of endothelial cell (EC) activation as clinically informative biomarkers to improve diagnosis, prognostic evaluation or risk-stratification of patients with sepsis.MethodsThe objective was to review the literature on the use of markers of EC activation as prognostic biomarkers in sepsis. MEDLINE was searched for publications using the keyword 'sepsis' and any of the identified endothelial-derived biomarkers in any searchable field. All clinical studies evaluating markers reflecting activation of ECs were included. Studies evaluating other exogenous mediators of EC dysfunction and studies of patients with malaria and febrile neutropenia were excluded.ResultsSixty-one studies were identified that fulfilled the inclusion criteria. Overall, published studies report positive correlations between multiple EC-derived molecules and the diagnosis of sepsis, supporting the critical role of EC activation in sepsis. Multiple studies also reported positive associations for mortality and severity of illness, although these results were less consistent than for the presence of sepsis. Very few studies, however, reported thresholds or receiver operating characteristics that would establish these molecules as clinically-relevant biomarkers in sepsis.ConclusionsMultiple endothelial-derived molecules are positively correlated with the presence of sepsis in humans, and variably correlated to other clinically-important outcomes. The clinical utility of these biomarkers is limited by a lack of assay standardization, unknown receiver operating characteristics and lack of validation. Additional large-scale prospective clinical trials will be required to determine the clinical utility of biomarkers of endothelial activation in the management of patients with sepsis.
| S-EPMC3396237 | biostudies-literature
Project description:Background and aimsPrevious experiments suggest that both increased endothelial cell apoptosis and endothelial surface glycocalyx shedding could play a role in the endothelial dysfunction and inflammation of athero-prone regions of the vasculature. We sought to elucidate the possibly synergistic mechanisms by which endothelial cell apoptosis and glycocalyx shedding promote atherogenesis.Methods4- to 6-week old male C57Bl/6 apolipoprotein E knockout (ApoE(-/-)) mice were fed a Western diet for 10 weeks and developed plaques in their brachiocephalic arteries.ResultsGlycocalyx coverage and thickness were significantly reduced over the plaque region compared to the non-plaque region (coverage plaque: 71 ± 23%, non-plaque: 97 ± 3%, p = 0.02; thickness plaque: 0.85 ± 0.15 μm, non-plaque: 1.2 ± 0.21 μm, p = 0.006). Values in the non-plaque region were not different from those found in wild type mice fed a normal diet (coverage WT: 92 ± 3%, p = 0.7 vs. non-plaque ApoE(-/-), thickness WT: 1.1 ± 0.06 μm, p = 0.2 vs. non-plaque ApoE(-/-)). Endothelial cell apoptosis was significantly increased in ApoE(-/-) mice compared to wild type mice (ApoE(-/-):64.3 ± 33.0, WT: 1.1 ± 0.5 TUNEL-pos/cm, p = 2 × 10(-7)). The number of apoptotic endothelial cells per unit length was 2 times higher in the plaque region than in the non-plaque region of the same vessel (p = 3 × 10(-5)). Increased expression of matrix metalloproteinase 9 co-localized with glycocalyx shedding and plaque buildup.ConclusionsOur results suggest that, in concert with endothelial apoptosis that increases lipid permeability, glycocalyx shedding initiated by inflammation facilitates monocyte adhesion and macrophage infiltration that promote lipid retention and the development of atherosclerotic plaques.
| S-EPMC5035621 | biostudies-literature
Project description:Inflammation and endothelial activation play a pivotal role in development and progression of diabetic retinopathy (DR), a vision-threatening complication of diabetes mellitus (DM) and the leading cause of blindness in the working age population. Easily accessible and validated biomarkers for DR early diagnosis and progression are required for use in clinical trials: here, we reviewed the available literature to understand the association of circulating levels of selected markers of inflammation and endothelial activation with the presence of nonproliferative and proliferative DR (NPDR and PDR) and investigate the relationship between their systemic and ocular levels. We additionally provide data synthesis and perform statistical analysis for interpretation of the collected evidence. CRP, IL-1β, IL-6, TNFα, sICAM1, and sVCAM1 circulating levels were increased in subjects with DM compared to healthy individuals. Moreover, TNFα and sVCAM1 showed increasing systemic levels with DR presence and severity; circulating CRP increased with the transition from no DR to NPDR, whereas IL-6 was increased in PDR compared to NDPR stages. The relationship between ocular and systemic concentrations of these proteins remained unclear due to the low number of studies with matched sampling. In conclusion, the available data supports the use of systemic biomarkers of inflammation and endothelial activation to identify DM status and DR severity. These systemic biomarkers are likely reflecting an overall state of inflammation and vascular activation in different tissues of the body, including the eyes. Prospective, longitudinal datasets are required to validate these biomarkers as predictors of early DR presence, of DR progression, or for disease monitoring.
| S-EPMC8496421 | biostudies-literature
Project description:The authors aimed to evaluate age-related differences in inflammation biomarkers during the first 72 h of hospitalization for sepsis. This was a secondary analysis of a prospective observational cohort of adult patients (n = 855) from 10 urban academic emergency departments with confirmed infection and two or more systemic inflammatory response syndrome criteria. Six inflammation-related biomarkers were analyzed-chemokine (CC-motif) ligand-23, C-reactive protein, interleukin-1 receptor antagonist, neutrophil gelatinase-associated lipocalin (NGAL), peptidoglycan recognition protein, and tumor necrosis factor receptor-1a (TNFR-1a)-measured at presentation and 3, 6, 12, 24, 48, or 72 h later. The median age was 56 (interquartile range, 43 - 72) years, and sepsis severity was 38% sepsis, 16% severe sepsis without shock, and 46% septic shock; the overall 30-day mortality was 12%. Older age was associated with higher sepsis severity: 41% of subjects aged 18 to 34 years had severe sepsis or septic shock compared with 71% for those aged 65 years or older (P < 0.001). In longitudinal models adjusting for demographics, comorbidities, and infection source, older age was associated with higher baseline values for chemokine (CC-motif) ligand-23, interleukin-1 receptor antagonist, NGAL, and TNFR-1a (all P < 0.05). However, older adults had higher mean values during the entire 72-h period only for NGAL and TNFR-1a and higher final 72-h values only for TNFR-1a. Adjustment or stratification by sepsis severity did not change the age-inflammation associations. Although older adults had higher levels of inflammation at presentation and an increased incidence of severe sepsis and septic shock, these age-related differences in inflammation largely resolved during the first 72 h of hospitalization.
| S-EPMC4101036 | biostudies-literature
Project description:BackgroundSepsis is a life-threatening illness with a challenging diagnosis. Rapid detection is the key to successful treatment of sepsis. To investigate diagnostic value, the plasma protein profiles of inflammatory biomarkers, cytokines, and endothelial functional markers were compared between healthy controls, SIRS, and septic patients.MethodsThe plasma protein profiles were performed by Luminex Assay in a cohort of 50 SIRS patients, 82 septic patients and 25 healthy controls. Fourteen plasma proteins were analyzed in the same cohort: IL-1β, IL-6, IL-8, IL-10, CCL-2, VEGF, VEGF-C, VEGFR2, CD62E, CD62P, MFG-E8, ICAM-1, TFPI, Urokinase.ResultIL-2R, IL-6, IL-8, IL-10, CCL-2, ICAM-1, and Urokinase were significantly higher in sepsis patients than SIRS patients. VEGF, IL-1β, CD62E, CD62P, MFG-E8, and TFPI have no statistical difference. VEGF-C, VEGFR2 were significantly different in SIRS patients than sepsis patients. Urokinase, ICAM-1, and VEGFR2 were significantly different between sepsis group and SIRS group. The AUCs of Urokinase, ICAM-1, and VEGFR2 and the combination for the diagnosis of sepsis were 0.650, 0.688, 0.643, and 0.741, respectively.ConclusionsMost patients have the higher level of several cytokines and developed endothelial cell injury in the initial phase of sepsis, Urokinase, ICAM-1, and VEGFR2 may be useful to evaluate severity and prognosis of sepsis patients.
| S-EPMC9281918 | biostudies-literature