Validation of Calprotectin As a Novel Biomarker For The Diagnosis of Pleural Effusion: a Multicentre Trial.
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SUBMITTER: Botana-Rial M
PROVIDER: S-EPMC7105479 | biostudies-literature | 2020 Mar
REPOSITORIES: biostudies-literature
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Validation of Calprotectin As a Novel Biomarker For The Diagnosis of Pleural Effusion: a Multicentre Trial.
Botana-Rial Maribel M Vázquez-Iglesias Lorena L Casado-Rey Pedro P Cadena María Páez de la MP Andrade-Olivié María Amalia MA Abal-Arca José J García-Nimo Laura L Ferreiro-Fernández Lucía L Valdés-Cuadrado Luis L San-José María Esther ME Rodríguez-Berrocal Francisco Javier FJ Fernández-Villar Alberto A
Scientific reports 20200330 1
Discriminating between malignant pleural effusion (MPE) and benign pleural effusion (BPE) remains difficult. Thus, novel and efficient biomarkers are required for the diagnosis of pleural effusion (PE). The aim of this study was to validate calprotectin as a diagnostic biomarker of PE in clinical settings. A total of 425 patients were recruited, and the pleural fluid samples collected had BPE in 223 cases (53.7%) or MPE in 137 patients (33%). The samples were all analysed following the same prev ...[more]
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Project description:BackgroundNovel non-invasive biomarkers for the precise diagnosis of malignancy in pleural effusion (PE) are needed. The aim of this study was to determine the diagnostic accuracy of calprotectin for predicting malignancy in patients with exudative PE.MethodsCalprotectin concentration was measured in 156 individuals diagnosed with exudative PE (67 malignant and 89 benign). Calprotectin accuracy for discriminating between malignant and benign PE was evaluated using receiver operating characteristic (ROC) curves. Univariate and multivariate logistic regression were performed to test the association between calprotectin levels and malignant PE.ResultsCalprotectin levels were significantly lower in malignant pleural fluid (257.2 ng ml(-1), range: 90.7-736.4) than benign effusions (2627.1 ng ml(-1), range: 21-9530.1). The area under the curve was 0.963. A cutoff point of ≤ 736.4 ng ml(-1) rendered a sensitivity of 100%, with a specificity of 83.15%, which could prove useful to delimit those patients with negative cytology tests that should be referred for more invasive diagnostic procedures. Logistic regression demonstrated a strong association between calprotectin and malignancy (adjusted OR 663.14).ConclusionCalprotectin predicts malignancy in pleural fluid with high accuracy and could be a good complement to cytological methods.
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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:In previous studies, measuring the levels of calprotectin in patients with pleural effusion (PE) was an exceptionally accurate way to predict malignancy. Here, we evaluated a rapid method for the measurement of calprotectin levels as a useful parameter in the diagnosis of malignant pleural effusion (MPE) in order to minimise invasive diagnostic tests. Calprotectin levels were measured with Quantum Blue® sCAL (QB®sCAL) and compared with the gold standard reference ELISA method. Calprotectin levels in patients with benign pleural effusion (BPE) were significantly higher (p < 0.0001) than for MPE patients. We measured the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive and negative likelihood ratios (LRs) for a cut-off value of ≤ 14,150 ng/mL; the diagnostic accuracy was 64%. The odds ratio for PE calprotectin levels was 10.938 (95% CI [4.133 - 28.947]). The diagnostic performance of calprotectin concentration was better for predicting MPE compared to other individual parameters. Comparison of two assays showed a slope of 1.084, an intercept of 329.7, and a Pearson correlation coefficient of 0.798. The Bland-Altman test showed a positive bias for the QB®sCAL method compared to ELISA fCAL®. Clinical concordance between both these methods was 88.5% with a Cohen kappa index of 0.76 (95% CI [0.68 - 0.84]). We concluded that QB®sCAL is a fast, reliable, and non-invasive diagnostic tool for diagnosing MPE and represents an alternative to ELISA that could be implemented in medical emergencies.
| S-EPMC8191907 | biostudies-literature
Project description:Symptomatic malignant pleural effusion is a common clinical problem. This condition is associated with very high mortality, with life expectancy ranging from 3 to 12 months. Studies are contributing evidence on an increasing number of therapeutic options (therapeutic thoracentesis, thoracoscopic pleurodesis or thoracic drainage, indwelling pleural catheter, surgery, or a combination of these therapies). Despite the availability of therapies, the management of malignant pleural effusion is challenging and is mainly focused on the relief of symptoms. The therapy to be administered needs to be designed on a case-by-case basis considering patient's preferences, life expectancy, tumour type, presence of a trapped lung, resources available, and experience of the treating team. At present, the management of malignant pleural effusion has evolved towards less invasive approaches based on ambulatory care. This approach spares the patient the discomfort caused by more invasive interventions and reduces the economic burden of the disease. A review was performed of the diagnosis and the different approaches to the management of malignant pleural effusion, with special emphasis on their indications, usefulness, cost-effectiveness, and complications. Further research is needed to shed light on the current matters of controversy and help establish a standardized, more effective management of this clinical problem.
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Project description:ObjectiveWe aimed to develop a radiomics nomogram based on computed tomography (CT) scan features and high-throughput radiomics features for diagnosis of malignant pleural effusion (MPE).MethodsIn this study, 507 eligible patients with PE (207 malignant and 300 benign) were collected retrospectively. Patients were divided into training (n = 355) and validation cohorts (n = 152). Radiomics features were extracted from initial unenhanced CT images. CT scan features of PE were also collected. We used the variance threshold algorithm and least absolute shrinkage and selection operator (LASSO) to select optimal features to build a radiomics model for predicting the nature of PE. Univariate and multivariable logistic regression analyzes were used to identify significant independent factors associated with MPE, which were then included in the radiomics nomogram.ResultsA total of four CT features were retained as significant independent factors, including massive PE, obstructive atelectasis or pneumonia, pleural thickening > 10 mm, and pulmonary nodules and/or masses. The radiomics nomogram constructed from 13 radiomics parameters and four CT features showed good predictive efficacy in training cohort [area under the curve (AUC) = 0.926, 95% CI 0.894, 0.951] and validation cohort (AUC = 0.916, 95% CI 0.860, 0.955). The calibration curve and decision curve analysis showed that the nomogram helped differentiate MPE from benign pleural effusion (BPE) in clinical practice.ConclusionThis study presents a nomogram model incorporating CT scan features and radiomics features to help physicians differentiate MPE from BPE.
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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.
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Project description:Background and Objective: The accurate differential diagnosis of tuberculous pleural effusion (TPE) from other exudative pleural effusions is often challenging. We aimed to validate the accuracy of complement component C1q in pleural fluid (PF) in diagnosing TPE. Methods: The level of C1q protein in the PF from 49 patients with TPE and 61 patients with non-tuberculous pleural effusion (non-TPE) was quantified by enzyme-linked immunosorbent assay, and the diagnostic performance was assessed by receiver operating characteristic (ROC) curves based on the age and gender of the patients. Results: The statistics showed that C1q could accurately diagnose TPE. Regardless of age and gender, with a cutoff of 6,883.9 ng/mL, the area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of C1q for discriminating TPE were 0.898 (95% confidence interval: 0.825-0.947), 91.8 (80.4-97.7), 80.3 (68.2-89.4), 78.9 (69.2-86.2), and 92.5 (82.6-96.9), respectively. In subgroup analysis, the greatest diagnostic accuracy was achieved in the younger group (≤ 50 years of age) with an AUC of 0.981 (95% confidence interval: 0.899-0.999) at the cutoff of 6,098.0 ng/mL. The sensitivity, specificity, PLR, NLR, PPV, and NPV of C1q were 95.0 (83.1-99.4), 92.3 (64.0-99.8), 97.4 (85.2-99.6), and 85.7 (60.6-95.9), respectively. Conclusion: Complement component C1q protein was validated by this study to be a promising biomarker for diagnosing TPE with high diagnostic accuracy, especially among younger patients.
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Project description:PurposeAlthough some parameters of positron emission tomography with 18F-fluorodeoxyglucose (18F-FDG) and computed tomography (PET-CT) are somehow helpful in differentiating malignant pleural effusion (MPE) from benign effusions, no individual parameter offers sufficient evidence for its implementation in the clinical practice. The aim of this study was to establish the diagnostic accuracy of a scoring system based on PET-CT (the PET-CT score) in diagnosing MPE.MethodsOne prospective derivation cohort of patients with pleural effusions (84 malignant and 115 benign) was used to develop the PET-CT score for the differential diagnosis of malignant pleural effusion. The PET-CT score was then validated in another independent prospective cohort (n = 74).ResultsThe PET-CT parameters developed for discriminating MPE included unilateral lung nodules and/or masses with increased 18F-FDG uptake (3 points); extrapulmonary malignancies (3 points); pleural thickening with increased 18F-FDG uptake (2 points); multiple nodules or masses (uni- or bilateral lungs) with increased 18F-FDG uptake (1 point); and increased pleural effusion 18F-FDG uptake (1 point). With a cut-off value of 4 points in the derivation cohort, the area under the curve, sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of the PET-CT score to diagnose MPE were 0.949 (95% CI: 0.908-0.975), 83.3% (73.6%-90.6%), 92.2% (85.7%-96.4%), 10.7 (5.6-20.1), and 0.2 (0.1-0.3), respectively.ConclusionsA simple-to-use PET-CT score that uses PET-CT parameters was developed and validated. The PET-CT score can help physicians to differentiate MPE from benign pleural effusions.
| S-EPMC6533224 | biostudies-literature
Project description:BackgroundThe simple, rapid, and accurate diagnosis of tuberculous pleural effusion (TPE) remains difficult. This study aimed to determine the accuracy of hepatocyte growth factor (HGF) in the diagnosis of TPE.MethodsWe quantified the expression of HGF, adenosine deaminase (ADA), and interferon gamma (IFN-γ) in pleural effusion (PE) in 97 TPE subjects and 116 non-TPE subjects using an enzyme-linked immunosorbent assay (ELISA) or a fully automatic biochemical analyzer. The diagnostic performance of these three biomarkers was evaluated using a receiver operating characteristic (ROC) curve of subjects by age and gender.ResultsWe discovered that the TPE group had much higher levels of HGF than the non-TPE group, regardless of age or gender, and that there was no statistically significant difference between the two groups' levels of HGF expression in peripheral plasma. In female TPE patients aged ≤65 years, the AUCs of TPE and non-TPE diagnosed by HGF, ADA or IFN-γ were 0.988, 0.964, and 0.827, respectively. HGF plus ADA had the highest diagnostic efficacy in female TPE patients aged ≤65 years. With HGF plus ADA having a cut-off value of 0.219 for distinguishing TPE from non-TPE, the area under the curve (AUC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), and negative predictive value (NPV) were, respectively, 0.998 (95% confidence interval [CI], 0.993-1.000), 100 (95% CI, 89.997-100.000), 96.667 (95% CI, 82.783-99.916), 97.222 (95% CI, 83.594-99.586), and 100.ConclusionThis study confirmed that HGF plus ADA has high diagnostic efficacy in younger female TPE patients and has the potential to be an excellent biomarker.
| S-EPMC10359098 | biostudies-literature
Project description:Malignant pleural effusion can complicate most cancers. It causes breathlessness and requires hospitalisation for invasive pleural drainages. Malignant effusions often herald advanced cancers and limited prognosis. Minimising time spent in hospital is of high priority to patients and their families. Various treatment strategies exist for the management of malignant effusions, though there is no consensus governing the best choice. Talc pleurodesis is the conventional management but requires hospitalisation (and substantial healthcare resources), can cause significant side effects, and has a suboptimal success rate. Indwelling pleural catheters (IPCs) allow ambulatory fluid drainage without hospitalisation, and are increasingly employed for management of malignant effusions. Previous studies have only investigated the length of hospital care immediately related to IPC insertion. Whether IPC management reduces time spent in hospital in the patients' remaining lifespan is unknown. A strategy of malignant effusion management that reduces hospital admission days will allow patients to spend more time outside hospital, reduce costs and save healthcare resources.The Australasian Malignant Pleural Effusion (AMPLE) trial is a multicentred, randomised trial designed to compare IPC with talc pleurodesis for the management of malignant pleural effusion. This study will randomise 146 adults with malignant pleural effusions (1:1) to IPC management or talc slurry pleurodesis. The primary end point is the total number of days spent in hospital (for any admissions) from treatment procedure to death or end of study follow-up. Secondary end points include hospital days specific to pleural effusion management, adverse events, self-reported symptom and quality-of-life scores.The Sir Charles Gairdner Group Human Research Ethics Committee has approved the study as have the ethics boards of all the participating hospitals. The trial results will be published in peer-reviewed journals and presented at scientific conferences.Australia New Zealand Clinical Trials Registry-ACTRN12611000567921; National Institutes of Health-NCT02045121.
| S-EPMC4225240 | biostudies-literature