SuPAR Surprises as a Biomarker of Invasive Outcomes in Pleural Infection.
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ABSTRACT:
SUBMITTER: Idell S
PROVIDER: S-EPMC7301739 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
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suPAR Surprises as a Biomarker of Invasive Outcomes in Pleural Infection.
Idell Steven S Lee Y C Gary YCG
American journal of respiratory and critical care medicine 20200601 12
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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:BackgroundTreatment modalities for malignant pleural effusion (MPE) are diverse. The objectives were to analyze actual clinical data from patients with MPE and pleural carcinomatosis and to compare the outcomes of different treatment modalities with regard to effectiveness, survival, morbidity, and mortality as well as the duration of hospitalization.MethodsPatients with pathologically proven pleural carcinomatosis or MPE from 2018 to 2020 were included in this retrospective-observational study with additional questionnaires. We identified four treatment modalities: (I) video-assisted thoracic surgery with pleurodesis (VATS, mechanical/chemical); (II) VATS with pleurodesis combined with indwelling pleural catheter (IPC) placement; (III) VATS (without pleurodesis) combined with IPC placement; and (IV) management with IPC placement alone.ResultsWe enrolled 91 patients aged 38-90 years who were treated by either VATS-pleurodesis (N=22), VATS-IPC placement (N=21), a combination of VATS with pleurodesis and IPC placement (N=22), or IPC placement alone (N=26). The mean survival time was 138.3 days. No significant differences were detected among treatment groups regarding the outcome of pleurodesis failure, either initially or later. Patients in the VATS-pleurodesis with IPC group experienced significantly more complications than those in the other treatment modality groups [odds ratio (OR): 3.288, P=0.026]. However, no statistically significant differences were observed regarding the type of adverse event and survival. Hypoalbuminemia, systemic therapy, and successful pleurodesis (P=0.008; P=0.011; P=0.044, respectively) were significantly correlated with survival. In multiple linear regression, hypoalbuminemia persisted as an independent predictor of survival (P=0.031). The type of intervention showed significant differences regarding the duration of hospitalization (P=0.017). IPC placement alone shortened the mean total hospitalization time by 7.9, 5.9, and 7.0 days compared to VATS-pleurodesis (P≤0.001), VATS-IPC placement (P=0.004), and VATS-pleurodesis with IPC placement (P≤0.001), respectively.ConclusionsThe survival time was very short, and each treatment group had pros and cons. Therefore, decisions should be made on a case-by-case basis. The use of an IPC, even if the lung is not trapped, can significantly reduce the length of hospital stay. VATS is needed when histology is needed. The ideal method for treating recurrent MPE should be simple, effective, and inexpensive, with minimal disturbance to the patient.
| S-EPMC10944730 | biostudies-literature
Project description:The No Surprises Act banned surprise billing and established a final-offer arbitration system, independent dispute resolution (IDR), to resolve disagreements between health plans and providers. One factor that arbiters must consider in the IDR process is the qualifying payment amount (QPA), the median contracted rate for the same or similar service in the same market as computed by health plans. We analyzed public IDR data from 2023 for the most common disputed professional service: evaluation and management of a moderate to severe emergency medicine visit. Providers won 86% of cases, with mean decisions 2.7 times the QPA. Private equity-backed providers won more often and higher monetary awards than other providers. The mean QPA was 2.4 times Medicare payments. Disputes were dominated by a small group of health plans and providers, so payments may not reflect the overall market for emergency services.
| S-EPMC11523055 | biostudies-literature
Project description:ImportanceThe No Surprises Act (NSA) banned surprise patient balance bills and established a binding arbitration system to resolve payment disputes between insurers and health care providers (eg, clinicians, hospitals, air ambulance organizations) for certain services, including air ambulance transportation. Understanding use and results of this new independent dispute resolution (IDR) system can inform ongoing adjustments to its implementation.ObjectiveTo describe the involved parties and outcomes of air ambulance NSA IDR cases.Design, setting, and participantsThis cross-sectional study assessed cases arbitrated through NSA IDR in 2023 as reported by the Centers for Medicare & Medicaid Services. Participants included air ambulance organizations and commercial insurers. Data were analyzed between August 1 and September 1, 2024.ExposuresFixed-wing and rotary transport disputes arbitrated under the NSA IDR system.Main outcomes and measuresThe activation components of fixed-wing and rotary transport disputes were evaluated with data from 2 distinct public files: (1) disclosed parties and outcomes relative to qualifying payment amounts (QPAs), the insurers' median of contracted rates for similar services in the region among similar health plans; and (2) monetary measures but without parties. The first file describes the insurers and organizations involved, including their ownership status, as well as the prevailing party and the offers and decisions relative to QPA. The second file describes QPAs, offers, and decisions monetarily and these are compared with Medicare's urban allowed amount.ResultsThere were 5678 IDR cases in 2023, comprising disputes for 4935 rotary and 743 fixed-wing transports. Air ambulance organizations offered a mean (SD) of 3.18 (4.20) times QPA, and insurers offered 1.39 (3.89) times QPA. Organizations won 4905 cases (86.4%) at a mean (SD) of 2.95 (4.12) times the QPA. A total of 3478 cases (61.3%) involved organizations owned by private equity investors, and these cases had higher prevailing offers relative to the QPA. Due to data suppression, analysis of financial measures was possible for 2897 of 5983 activation cases (48.4%), among which the mean (SD) QPA offer was $15 561.08 ($9730.97) (3.74 [2.31] times Medicare), and the winning offer was $32 463.70 ($9987.17) (7.82 [2.39] times Medicare).Conclusions and relevanceIn this cross-sectional study of air ambulance payment disputes, air ambulance organizations won most cases, requiring insurers to pay more in these cases. Notably, the NSA does not require changes to patient cost-sharing based on IDR outcomes. Assessment of the financial metrics and outcomes of air ambulance cases was limited due to missing and masked information. Continued monitoring of air ambulance IDR cases is needed to assess the impacts of the NSA.
| S-EPMC11877184 | 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:BackgroundDeregulation in the urokinase-type plasminogen activator receptor (uPA/uPAR) system is reported in many diseases where the immune system is activated. During SARS-CoV-2 infection, a rise in soluble uPAR (suPAR) levels has been detected and its concentration above 6 µg/L predicts worsening to severe respiratory failure 14 days earlier, with a positive predictive value of 85.9%, and was the prerequisite for a treatment with anakinra, a recombinant IL-1 receptor antagonist that blocks the activity of both IL-1α and IL-1β.ObjectivesTo compare suPAR concentrations measured by CHORUS suPAR on CHORUS TRIO instrument of DIESSE with the commercially available suPARnostic (ViroGates) ELISA assay.DesignA single-centre, non-pharmacological, diagnostic study was performed.ResultsA total of 522 serum samples from patients with COVID-19 were tested for suPAR. CHORUS suPAR resulted accurate and reliable, with a high grade of specificity (97.9%), accuracy (97.3%) and sensitivity (96.9%). The median concentration of suPAR, as determined with CHORUS suPAR, was 6.8 µg/L (interquartile range 4.5-9.7) in patients with moderate disease (n = 465) and 8.5 µg/L (interquartile range 5.4-10.6) in patients with severe disease. Among patients with moderate and severe disease, 60.6% and 71.9%, respectively, reached the cut-off concentration of suPAR ⩾6 µg/L, defining their illness severity and suggesting eligibility to anakinra treatment.ConclusionCHORUS suPAR kit resulted as sensitive, specific, accurate and able to quantify suPAR concentrations in patients with moderate and severe COVID-19.
| S-EPMC10687937 | biostudies-literature
Project description:BackgroundNumerous studies have described the critical importance of interleukin (IL) -36γ in host defense against lung infections, but it is unknown whether it plays a role in infectious pleural effusion (IPE). This study aimed to examine the levels of IL-36γ in pleural effusions of different etiologies and evaluate the diagnostic accuracy of IL-36γ in the differential diagnosis of IPE.MethodsA total of 112 individuals was enrolled in this research. IL-36γ levels in pleural fluids of all 112 patients were measured by enzyme-linked immunosorbent assay (ELISA). We also characterized these markers' diagnostic values across various groups.ResultsPatients with tuberculous pleural effusion (TPE) and parapneumonic effusion (PPE) had exhibited markedly higher IL-36γ levels in their pleural fluid than the malignant pleural effusion (MPE) and transudative effusion patients. Furthermore, the IL-36γ concentrations in TPE patients were evidently higher than in uncomplicated parapneumonic effusion (UPPE) patients but significantly lower than in complicated parapneumonic effusion (CPPE)/empyema patients. Pleural fluid IL-36γ is a useful marker to differentiate TPE from UPPE, at a cut-off value for 657.5 pg/ml (area under the curve = 0.904, p < 0.0001) with 70.0% sensitivity and 95.7% specificity.ConclusionsThe elevated IL-36γ in pleural effusion may be used as a novel biomarker for infectious pleural effusion diagnosis, particularly in patients with CPPE/empyema, and is a potentially promising biomarker to differentiate between TPE and UPPE.
| S-EPMC9833963 | 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