SuPAR Surprises as a Biomarker of Invasive Outcomes in Pleural Infection.
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ABSTRACT:
SUBMITTER: Idell S
PROVIDER: S-EPMC7301739 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Rationale: Parapneumonic effusions have a wide clinical spectrum. The majority settle with conservative management but some progress to complex collections requiring intervention. For decades, physicians have relied on pleural fluid pH to determine the need for chest tube drainage despite a lack of prospective validation and no ability to predict the requirement for fibrinolytics or thoracic surgery.Objectives: To study the ability of suPAR (soluble urokinase plasminogen activator receptor), a potential biomarker of pleural fluid loculation, to predict the need for invasive management compared with conventional fluid biomarkers (pH, glucose, and lactate dehydrogenase) in parapneumonic effusions.Methods: Patients presenting with pleural effusions were prospectively recruited to an observational study with biological samples stored at presentation. Pleural fluid and serum suPAR levels were measured using the suPARnostic double-monoclonal antibody sandwich ELISA on 93 patients with parapneumonic effusions and 47 control subjects (benign and malignant effusions).Measurements and Main Results: Pleural suPAR levels were significantly higher in effusions that were loculated versus nonloculated parapneumonic effusions (median, 132 ng/ml vs. 22 ng/ml; P < 0.001). Pleural suPAR could more accurately predict the subsequent insertion of a chest tube with an area under the curve (AUC) of 0.93 (95% confidence interval, 0.89-0.98) compared with pleural pH (AUC 0.82; 95% confidence interval, 0.73-0.90). suPAR was superior to the combination of conventional pleural biomarkers (pH, glucose, and lactate dehydrogenase) when predicting the referral for intrapleural fibrinolysis or thoracic surgery (AUC 0.92 vs. 0.76).Conclusions: Raised pleural suPAR was predictive of patients receiving more invasive management of parapneumonic effusions and added value to conventional biomarkers. These results need validation in a prospective multicenter trial.
| S-EPMC7301729 | biostudies-literature
Project description:Studies of large free-ranging mammals incorporating physiological measurements typically require the collection of urine or faecal samples, due to ethical and practical concerns over trapping or darting animals. However, there is a dearth of validated biomarkers of immune activation and inflammation that can be measured non-invasively. We here evaluate the utility of urinary measurements of the soluble form of the urokinase plasminogen activator receptor (suPAR), for use as a health marker in studies of wild large mammals. We investigate how urinary suPAR concentrations change in response to viral infection and surgical trauma (inflammation), comparing it to the measurement of a marker of cellular immune activation, urinary neopterin (uNEO), in captive rhesus macaques. We then test the field utility of urinary suPAR, assessing the effects of soil and faecal contamination, sunlight, storage at different temperatures, freeze-thaw cycles, and lyophilization. We find that suPAR concentrations rise markedly in response to both infection and surgery-associated inflammation, unlike uNEO concentrations, which only rise in response to the former. Our field validation demonstrates that urinary suPAR is reasonably robust to many of the issues associated with field collection, sample processing, and storage, as long as samples can be stored in a freezer. Urinary suPAR is thus a promising biomarker applicable for monitoring various aspects of health in wild primates and potentially also other large mammals.
| S-EPMC7062102 | biostudies-literature
Project description:BackgroundTo understand and measure the association between chronic inflammation, aging, and age-related diseases, broadly applicable standard biomarkers of systemic chronic inflammation are needed. We tested whether elevated blood levels of the emerging chronic inflammation marker soluble urokinase plasminogen activator receptor (suPAR) were associated with accelerated aging, lower functional capacity, and cognitive decline.MethodsWe used data from the Dunedin Study, a population-representative 1972-1973 New Zealand birth cohort (n = 1037) that has observed participants to age 45 years. Plasma suPAR levels were analyzed at ages 38 and 45 years. We performed regression analyses adjusted for sex, smoking, C-reactive protein, and current health conditions.ResultsOf 997 still-living participants, 875 (88%) had plasma suPAR measured at age 45. Elevated suPAR was associated with accelerated pace of biological aging across multiple organ systems, older facial appearance, and with structural signs of older brain age. Moreover, participants with higher suPAR levels had greater decline in physical function and cognitive function from childhood to adulthood compared to those with lower suPAR levels. Finally, improvements in health habits between ages 38 and 45 (smoking cessation or increased physical activity) were associated with less steep increases in suPAR levels over those years.ConclusionsOur findings provide initial support for the utility of suPAR in studying the role of chronic inflammation in accelerated aging and functional decline.
| S-EPMC7812430 | biostudies-literature
Project description:Systemic chronic inflammation (SCI) is persistent, health-damaging, low-grade inflammation that plays a major role in immunosenescence and in development and progression of many diseases. But currently, there are no recognized standard biomarkers to assess SCI levels alone, and SCI is typically measured by combining biomarkers of acute inflammation and infection, e.g., CRP, IL-6, and TNFα. In this review, we highlight 10 properties and characteristics that are shared by the blood protein soluble urokinase plasminogen activator receptor (suPAR) and SCI, supporting the argument that suPAR is a biomarker of SCI: (1) Expression and release of suPAR is upregulated by immune activation; (2) uPAR and suPAR exert pro-inflammatory functions; (3) suPAR is associated with the amount of circulating immune cells; (4) Blood suPAR levels correlate with the levels of established inflammatory biomarkers; (5) suPAR is minimally affected by acute changes and short-term influences, in contrast to many currently used markers of systemic inflammation; (6) Like SCI, suPAR is non-specifically associated with multiple diseases; (7) suPAR and SCI both predict morbidity and mortality; (8) suPAR and SCI share the same risk factors; (9) suPAR is associated with risk factors and outcomes of inflammation above and beyond other inflammatory biomarkers; (10) The suPAR level can be reduced by anti-inflammatory interventions and treatment of disease. Assessing SCI has the potential to inform risk for morbidity and mortality. Blood suPAR is a newer biomarker which may, in fact, be a biomarker of SCI since it is stably associated with inflammation and immune activation; shares the same risk factors as many age-related diseases; is both elevated by and predicts age-related diseases. There is strong evidence that suPAR is a prognostic marker of adverse events, morbidity, and mortality. It is associated with immune activity and prognosis across diverse conditions, including kidney disease, cardiovascular disease, cancer, diabetes, and inflammatory disorders. Thus, we think it likely represents a common underlying disease-process shared by many diseases; that is, SCI. We review the supporting literature and propose a research agenda that can help test the hypothesis that suPAR indexes SCI, with the potential of becoming the new gold standard for measuring SCI.
| S-EPMC8674945 | biostudies-literature
Project description:Pleural infection remains an important cause of mortality. This study aimed to investigate worldwide patterns of pre-existing comorbidities and clinical outcomes of patients with pleural infection. Studies reporting on adults with pleural infection between 2000 and 2017 were identified from a search of Embase and MEDLINE. Articles reporting exclusively on tuberculous, fungal or post-pneumonectomy infection were excluded. Two reviewers assessed 20 980 records for eligibility. 211 studies met the inclusion criteria. 134 articles (227 898 patients, mean age 52.8 years) reported comorbidity and/or outcome data. The majority of studies were retrospective observational cohorts (n=104, 78%) and the most common region of reporting was East Asia (n=33, 24%) followed by North America (n=27, 20%). 85 articles (50 756 patients) reported comorbidity. The median (interquartile range (IQR)) percentage prevalence of any comorbidity was 72% (58-83%), with respiratory illness (20%, 16-32%) and cardiac illness (19%, 15-27%) most commonly reported. 125 papers (192 298 patients) reported outcome data. The median (IQR) length of stay was 19 days (13-27 days) and median in-hospital or 30-day mortality was 4% (IQR 1-11%). In regions with high-income economies (n=100, 74%) patients were older (mean 56.5 versus 42.5 years, p<0.0001), but there were no significant differences in prevalence of pre-existing comorbidity nor in length of hospital stay or mortality. Patients with pleural infection have high levels of comorbidity and long hospital stays. Most reported data are from high-income economy settings. Data from lower-income regions is needed to better understand regional trends and enable optimal resource provision going forward.
| S-EPMC6860993 | biostudies-literature
Project description:Malignant pleural mesothelioma (MPM) is a highly aggressive and therapy resistant pleural malignancy that is caused by asbestos exposure. MPM is associated with poor prognosis and a short patient survival. The survival time is strongly influenced by the subtype of the tumor. Dyspnea and accumulation of pleural effusion in the pleural cavity are common symptoms of MPM. The diagnostic distinction from other malignancies and reactive conditions is done using histopathology or cytopathology, always supported by immunohistochemistry, and sometimes also by analyses of soluble biomarkers in effusion supernatant. We evaluated the soluble angiogenesis related molecules as possible prognostic and diagnostic biomarkers for MPM by Luminex multiplex assay. Pleural effusion from 42 patients with malignant pleural mesothelioma (MPM), 36 patients with adenocarcinoma (AD) and 40 benign (BE) effusions were analyzed for 10 different analytes that, in previous studies, were associated with angiogenesis, consisting of Angiopoietin-1, HGF, MMP-7, Osteopontin, TIMP-1, Galectin, Mesothelin, NRG1-b1, Syndecan-1 (SDC-1) and VEGF by a Human Premixed Multi-Analyte Luminex kit. We found that shed SDC-1 and MMP-7 levels were significantly lower, whereas Mesothelin and Galectin-1 levels were significantly higher in malignant mesothelioma effusions, compared to adenocarcinoma. Galectin-1, HGF, Mesothelin, MMP-7, Osteopontin, shed SDC-1, NRG1-?1, VEGF and TIMP-1 were significantly higher in malignant pleural mesothelioma effusions compared to benign samples. Moreover, there is a negative correlation between Mesothelin and shed SDC-1 and positive correlation between VEGF, Angiopoietin-1 and shed SDC-1 level in the pleural effusion from malignant cases. Shed SDC-1 and VEGF have a prognostic value in malignant mesothelioma patients. Collectively, our data suggest that MMP-7, shed SDC-1, Mesothelin and Galectin-1 can be diagnostic and VEGF and SDC-1 prognostic markers in MPM patients. Additionally, Galectin-1, HGF, Mesothelin, MMP-7, Osteopontin, shed SDC-1 and TIMP-1 can be diagnostic for malignant cases.
| S-EPMC7464384 | biostudies-literature
Project description:Surgical trauma induces activation of the immune system and may cause an increase of inflammatory biomarkers tested postoperatively in septic patients treated for bloodstream infection. The aim of this study was to determine the impact of surgical interventions on the novel sepsis biomarker soluble urokinase plasminogen activator receptor (suPAR) and to compare results with those of routine laboratory parameters CRP, PCT, and IL-6 in patients with culture-proven bloodstream infection. Forty-six adult patients with positive blood culture undergoing minor or major surgical intervention were investigated, 12 blood culture positive patients served as control group. Blood was collected 24 hours before and after surgical intervention for determination of the sepsis biomarkers suPAR, CRP, PCT, and IL-6. Within the surgical study cohort, a non-significant increase of suPAR, CRP, and PCT was observed postoperatively (p 0.642; p 0.773; p 0.087). In contrast, a slight decrease of IL-6 (p 0.599) was observed. A significant correlation was calculated for the pre- and postoperative difference of CRP (p 0.028) and PCT (p 0.008) and type of surgical intervention received: after minor surgical intervention only PCT decreased significantly (p<0.001), while after major surgical interventions no significant differences were observed for all biomarkers evaluated. In the control group, a significant decrease of CRP (p 0.005) and PCT (p 0.005) was observed. In patients treated adequately for bloodstream infections, postoperative suPAR levels remained uninfluenced of the surgical trauma and might therefore be a reliable parameter for postoperative infectious monitoring. After minor surgical intervention, PCT seems to be the most reliable parameter.
| S-EPMC6301737 | biostudies-literature
Project description:Background and objectivesClinical pathways are evidence based multidisciplinary team approaches to optimize patient care. Pleural diseases are common and accounted for 3.4 billion US $ in 2014 US inpatient aggregate charges (HCUPnet data). An institutional clinical pathway ("pleural pathway") was implemented in conjunction with a dedicated pleural service. Design, implementation, and outcomes of the pleural pathway (from August 1, 2014, to July 31, 2015) in comparison to a previous era (from August 1, 2013, to July 31, 2014) are described.MethodsTuality Healthcare is a 215-bed community healthcare system in Hillsboro, OR, USA. With the objective of standardizing pleural disease care, locally adapted British Thoracic Society guidelines and a centralized pleural service were implemented in the "pathway" era. System-wide consensus regarding institutional guidelines for care of pleural disease was achieved. Preimplementation activities included training, acquisition of ultrasound equipment, and system-wide education. An audit database was set up with the intent of prospective audits. An administrative database was used for harvesting outcomes data and comparing them with the "prior to pathway" era.Results54 unique consults were performed. A total of 55 ultrasound examinations and 60 pleural procedures were performed. All-cause inpatient pleural admissions were lower in the "pathway" era (n = 9) compared to the "prior to pathway" era (n = 17). Gains in average case charges (21,737$ versus 18,818.2$/case) and average length of stay (3.65 versus 2.78 days/case) were seen in the "pathway" era.ConclusionA "pleural pathway" and a centralized pleural service are associated with reduction in case charges, inpatient admissions, and length of stay for pleural conditions.
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Project description:Viruses are the most prevalent infectious agents, populating almost every ecosystem on earth. Most viruses carry only a handful of genes supporting their replication and the production of capsids. It came as a great surprise in 2003 when the first giant virus was discovered and found to have a >1 Mbp genome encoding almost a thousand proteins. Following this first discovery, dozens of giant virus strains across several viral families have been reported. Here, we provide an updated quantitative and qualitative view on giant viruses and elaborate on their shared and variable features. We review the complexity of giant viral proteomes, which include functions traditionally associated only with cellular organisms. These unprecedented functions include components of the translation machinery, DNA maintenance, and metabolic enzymes. We discuss the possible underlying evolutionary processes and mechanisms that might have shaped the diversity of giant viruses and their genomes, highlighting their remarkable capacity to hijack genes and genomic sequences from their hosts and environments. This leads us to examine prominent theories regarding the origin of giant viruses. Finally, we present the emerging ecological view of giant viruses, found across widespread habitats and ecological systems, with respect to the environment and human health.
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Project description:Malignant pleural mesothelioma (MPM) is a lethal thoracic malignancy whose incidence is still increasing worldwide. MPM is characterized by frequent inactivation of tumor-suppressor genes (TSGs), e.g., the homozygous deletion of CDKN2A/2B and various genetic alterations that inactivate BAP1, NF2, LATS1/2, and TP53. The leading cause for the poor prognosis of patients with MPM is the lack of effective treatment options, with conventional chemotherapy being the standard of care in the clinic, which has remained unchanged for almost 20 years. Precision oncology, a burgeoning effort to provide precise cancer treatment tailored to unique molecular changes in individual patients, has made tremendous progress in the last decade in several cancers, but not in MPM. Recent studies indicate a high degree of tumor heterogeneity in MPM and the importance to optimize histological and molecular classifications for improved treatment. In this review, we provide an up-to-date overview of recent advances in MPM by focusing on new stratifications of tumor subgroups, specific vulnerabilities associated with functional loss of TSGs and other biomarkers, and potential clinical implications. The molecularly based subdivisions not only deepen our understanding of MPM pathobiology, but more importantly, they may raise unprecedented new hopes for personalized treatment of MPM patients with biomarker-guided targeted and immunotherapies.
| S-EPMC7672749 | biostudies-literature