Pleural Fluid GSDMD is a Novel Biomarker for the Early Differential Diagnosis of Pleural Effusion

2020 ◽  
Author(s):  
Pu Li ◽  
Jing Shi ◽  
Lijing Zhou ◽  
Bo Wang ◽  
Lijun Zhang ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Pleural Effusion ◽  
Pleural Fluid ◽  
Roc Curve ◽  
Early Stage ◽  
Statistical Significance ◽  
Sandwich Elisa ◽  
Predictive Performance ◽  
Diagnostic Efficiency ◽  
Diagnostic Role

Abstract Introduction: To accurate differential diagnosis of pleural effusion (PE) is still a big challenge. Gasdermin D (GSDMD), controlling pyroptosis in cells, has multiple physiological functions. The diagnostic role of GSDMD in PE remains unknown.Methods: Sandwich ELISA kits that we developed were applied to measure the level of GSDMD for 335 patients with the definite cause of PE, including transudative pleural effusion, tuberculous pleural effusion (TPE), parapneumonic pleural effusion (PPE), and malignant pleural effusion (MPE). Clinical follow up of 40 cases of PPE were conducted and divided into efficacy group and non-efficacy group according to therapeutic outcome. The receiver operating characteristic (ROC) curve was conducted to explore the diagnostic and predictive performance of GSDMD. Nucleated cells (NCs) in pleural effusion were isolated and further infected with bacteria to verify the cell source of GSDMD.Results: In this study, there was prominent statistical significance among the concentration of GSDMD in these four groups (all p < 0.0001, except between MPE and PPE). ROC curve indicated that GSDMD can be an efficient biomarker for differential diagnosis of transudative pleural effusion and other groups (all AUC ＞ 0.973). Noteworthily, the highest AUC belonged to tuberculosis diagnosis of 0.990, and the sensitivity and specificity were 100% and 97.53%. The combination of GSDMD, adenosine deaminase (ADA) and lactate dehydrogenase (LDH) will further improve the diagnostic efficiency especially between TPE and PPE (AUC = 0.968). The AUC of GSDMD change at day 4 could predict the therapeutic effect at an early stage was 0.945 (P < 0.0001). Interestingly, bacterial infection experiments further confirm that the pleural fluid GSDMD was expressed and secreted mainly by the NCs. Conclusion: GSDMD and its combination not only candidate as the potentially novel biomarkers to separate PEs early and effectively, but also monitor disease progression.

scholarly journals Pleural Fluid GSDMD Is a Novel Biomarker for the Early Differential Diagnosis of Pleural Effusion

2021 ◽  
Vol 12 ◽  
Author(s):  
Pu Li ◽  
Jing Shi ◽  
Lijing Zhou ◽  
Bo Wang ◽  
Li Jun Zhang ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Pleural Effusion ◽  
Diagnostic Accuracy ◽  
Pleural Fluid ◽  
Early Stage ◽  
Sandwich Elisa ◽  
Diagnostic Efficiency ◽  
Parapneumonic Pleural Effusion ◽  
Diagnostic Role ◽  
Tuberculosis Diagnosis

ObjectiveGasdermin D (GSDMD), controlling pyroptosis in cells, has multiple physiological functions. The diagnostic role of GSDMD in pleural effusion (PE) remains unknown.MethodsSandwich ELISA kits that we developed were applied to measure the level of GSDMD for 335 patients with a definite cause of PE, including transudative PE, tuberculous pleural effusion (TPE), parapneumonic pleural effusion (PPE), and malignant pleural effusion (MPE). The diagnostic accuracy of Light’s criteria vs. the new marker GSDMD was performed. Clinical follow-up of 40 cases of PPE was conducted and divided into efficacy and non-efficacy groups according to the therapeutic outcome. Nucleated cells (NCs) in PE were isolated and further infected with bacteria to verify the cell source of GSDMD.ResultsThe diagnostic accuracy of GSDMD for the diagnosis of PE were 96% (sensitivity) and 94% (specificity). The receiver operating characteristic (ROC) curve indicated that GSDMD can be an efficient biomarker for the differential diagnosis of transudative PE and other groups (all AUC &gt; 0.973). Noteworthily, the highest AUC belonged to tuberculosis diagnosis of 0.990, and the cut-off value was 18.40 ng/mL. Moreover, the same cut-off value of PPE and MPE was 9.35 ng/mL. The combination of GSDMD, adenosine deaminase (ADA), and lactate dehydrogenase (LDH) will further improve the diagnostic efficiency especially between TPE and PPE (AUC = 0.968). The AUC of GSDMD change at day 4, which could predict the therapeutic effect at an early stage, was 0.945 (P &lt; 0.0001). Interestingly, bacterial infection experiments further confirm that the pleural fluid GSDMD was expressed and secreted mainly by the NCs.ConclusionGSDMD and its combination are candidates as a potentially novel biomarker not only to separate PEs early and effectively, but also monitor disease progression.

Assessment of a panel of miRNAs in serum and pleural fluid for the differential diagnosis of malignant and benign pleural effusion

2021 ◽  
pp. 1-11
Author(s):  
Li-Rong Zhu ◽  
Rong-Xia Yuan ◽  
Xian-Bin Xia ◽  
Yi Wang ◽  
Yu-Min Zhu ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Pleural Effusion ◽  
Pleural Fluid ◽  
Roc Curve ◽  
Operating Characteristic ◽  
Aberrant Expression ◽  
Qrt Pcr ◽  
Individual Mirnas ◽  
Tuberculous Pleurisy ◽  
Benign Pleural Effusion

BACKGROUND: Differential diagnosis between malignant pleural effusion (MPE) and benign pleural effusion (BPE) remains a clinical challenge. OBJECTIVE: The aim of the study is to assess the efficacy of the serum and pleural fluid (PF) miRNA panels in distinguishing MPE from BPE. METHODS: Fourteen candidate miRNAs which were shown aberrant expression in lung cancer based on previous studies were tested by quantitative real-time PCR (qRT-PCR) in 20 MPE patients and 20 BPE patients. Significantly aberrantly expressed miRNAs were further assessed by qRT-PCR in all patients enrolled in this study. A receiver operating characteristic (ROC) curve was constructed, and the area under the ROC curve (AUC) was calculated to evaluated the diagnostic performance of the miRNAs. RESULTS: miR-21, miR-29c and miR-182 were found to be significantly aberrantly expressed in the serum and PF of MPE patients. The AUCs for the combination of miR-21, miR-29c and miR-182 in serum and PF were 0.832 and 0.89 respectively in distinguishing MPE from infection-associated PE including tuberculous pleurisy and parapneumonia PE, and 0.866 and 0.919 respectively for differentiating MPE from heart failure-associated PE, which were superior to AUC of each individual miRNAs. CONCLUSIONS: miR-21, miR-29c and miR-182 in serum and PF could be useful biomarkers for MPE of diagnosis.

scholarly journals The Differential Diagnostic Values of Cytokine Levels in Pleural Effusions

2005 ◽  
Vol 2005 (1) ◽  
pp. 2-8 ◽  
Author(s):  
Saadet Akarsu ◽  
A. Nese Citak Kurt ◽  
Yasar Dogan ◽  
Erdal Yilmaz ◽  
Ahmet Godekmerdan ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Pleural Effusion ◽  
Pleural Fluid ◽  
Parapneumonic Effusion ◽  
Pleural Effusions ◽  
Tuberculous Pleural Effusion ◽  
Cytokine Levels ◽  
Diagnostic Values

The aim is to examine whether the changes in pleural fluid interleukin (IL)-1β, IL-2, IL-6, and IL-8 levels were significant in differential diagnosis of childhood pleural effusions. IL-1β, IL-2, IL-6, and IL-8 levels in pleural fluids of all 36 patients were measured. The levels of IL-1β, IL-2, IL-6, and IL-8 in pleural fluids were statistically significantly higher in the transudate group compared with those of the exudate group. The levels of IL-1β, IL-6, and IL-8 were also found to be statistically significantly higher in the empyema group compared with both the parapneumonic and the tuberculous pleural effusion groups. The levels of IL-2 and IL-6 were detected to be statistically significantly higher in the tuberculous pleural effusion group in comparison with those of the parapneumonic effusion group. The results showed that pleural fluids IL-1β, IL-2, IL-6, and IL-8 could be used in pleural fluids exudate and transudate distinction.

scholarly journals CEA and ADA in Pleural Fluid for Differential Malignant Pleural Effusion and Tuberculous Pleural Effusion

2021 ◽  
Author(s):  
Jianhong Yu ◽  
Qirui Cai
Keyword(s):  
Pleural Effusion ◽  
Pleural Fluid ◽  
Roc Curve ◽  
Malignant Pleural Effusion ◽  
Diagnostic Value ◽  
Diagnostic Model ◽  
Diagnostic Efficacy ◽  
Tuberculous Pleural Effusion ◽  
Diagnostic Models ◽  
Independent Risk Factors

Abstract Objective This study aimed to establish a predictive model based on the clinical manifestations and laboratory findings in pleural fluid of patients with pleural effusion for the differential diagnosis of malignant pleural effusion (MPE) and tuberculous pleural effusion (TPE). Methods Clinical data and laboratory indices of pleural fluid were collected from patients with malignant pleural effusion and tuberculous pleural effusion in Zigong First People's Hospital between January 2019 and June 2020，and were compared between the two groups. Independent risk factors or Independent protective factors for malignant pleural effusion were investigated using multivariable logistic regression analysis. Receiver operating characteristic curve (ROC) analysis was performed to assess the diagnostic performance of factors with independent effects, and combined diagnostic models were established based on two or more factors with independence effect. ROC curve was used to evaluate the diagnostic ability of each model, and the fit of the eath model was measured using Hosmer-Lemeshow goodness-of-fit test. Results Patients with MPE were older than those with TPE, the rate of fever of patients with MPE was lower than that of patients with TPE, and these differences were statistically significant (p < 0.05). Carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin-19 fragment antigen (CYFRA21-1), cancer antigen 125 (CA125), and glucose (GLU) levels in the pleural fluid were higher, but total protein (TP), albumin (ALB) and Adenosine deaminase (ADA) levels in the pleural fluid were lower in MPE patients than in TPE patients, and the differences were statistically significant (P<0.05). In multivariate logistic regression analysis, CEA and NSE levels in the pleural fluid were independent risk factors for MPE, whereas ADA levels in pleural fluid and fever were independent protective factors for MPE. The differential diagnostic value of pleural fluid CEA and pleural fluid ADA for MPE and TPE were higher than that of pleural fluid NSE（p<0.05） and the area under the ROC curve was 0.901, 0.892, and 0.601, respectively. Four different binary logistic diagnostic models were established based on pleural fluid CEA combined with pleural fluid NSE, pleural fluid ADA or ( and ) fever. Among them, the model established with the combination of pleural fluid CEA and pleural fluid ADA (logit (P) = 0.513 + 0.457*CEA-0.101*ADA) had the highest diagnostic value for malignant pleural effusion, and its predictive accuracy was high with an area under the ROC curve of 0.968 [95% confidence interval (0.947, 0.988)]. But the diagnostic efficacy of the diagnostic model could not be improved by adding pleural fluid NSE and fever. Conclusion The model established with the combination of CEA and ADA in the pleural fluid has a high differential diagnostic value for malignant pleural effusion and tuberculous pleural effusion, and NSE in the pleural fluid and fever cannot improve the diagnostic efficacy of the diagnostic model.

scholarly journals Clinical significance of fucosylated GP73 in the differential diagnosis of hepatocellular carcinoma

2018 ◽  
Vol 33 (4) ◽  
pp. 439-446 ◽  
Author(s):  
Yunsheng Zhao ◽  
Lina Zhang ◽  
Lijing Huo ◽  
Liu Pei ◽  
Qiuping Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Differential Diagnosis ◽  
Roc Curve ◽  
Enzyme Linked Immunosorbent Assay ◽  
Diagnostic Efficiency ◽  
Roc Curve Analysis ◽  
Diagnostic Significance ◽  
Node Metastasis ◽  
Tumor Node Metastasis Stage ◽  
Normal Controls

Objective: To investigate the clinical value of fucosylated GP73 (Fuc-GP73) levels for differential diagnosis of hepatocellular carcinoma from other liver diseases. Methods: Serum specimens were collected from 50 patients with hepatocellular carcinoma, 60 patients with other digestive system diseases (ODSD), and 40 normal controls. Lectin affinity chromatography column combining with the enzyme-linked immunosorbent assay (ELISA) using the ELISA index was utilized to measure the level of Fuc-GP73. By receiver operating characteristic (ROC) curve analysis its sensitivity and specificity were used to evaluate the diagnostic significance of Fuc-GP73 in hepatocellular carcinoma. Results: The median serum Fuc-GP73 level of hepatocellular carcinoma (20.4 μg/L) was much higher than that of ODSD patients (1.8 μg/L) and the normal controls group (0.3 μg/L), significantly ( P <0.01). There was no significant correlation between serum Fuc-GP73 level and sex, age, and tumor size in the hepatocellular carcinoma group ( P > 0.05); however, it was related to tumor, node, metastasis stage and lymph node metastasis ( P <0.05). The area under the ROC curve (AUC) of Fuc-GP73 to detect hepatocellular carcinoma alone was 0.885; with the prespecified specificity of 95%, the sensitivity and the cutoff value were 82% and 3.1 μg/L. In addition, the combined test of Fuc-GP73 with other biomarkers can improve the clinical diagnostic efficiency; the AUC can reach to 0.983; and with the prespecified specificity of 95% its sensitivity increased to 94%. Conclusion: Fuc-GP73 can act as a superior glycobiomarker for the differential diagnosis of hepatocellular carcinoma; its combined detection with other biomarkers can improve diagnostic accuracy.

The diagnostic role of pleural fluid and serum Pentraxin-3 levels in the determination of the etiology of pleural effusion

2017 ◽  
Author(s):  
Fatma Çiftci ◽  
Gulden Bilgin ◽  
Ayse Naz Ozcan ◽  
Ozlem Dogan ◽  
Aycan Yuksel ◽  
...  
Keyword(s):  
Pleural Effusion ◽  
Pleural Fluid ◽  
Pentraxin 3 ◽  
Diagnostic Role

scholarly journals A retrospective study on the combined biomarkers and ratios in serum and pleural fluid to distinguish the multiple types of pleural effusion

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Liyan Lin ◽  
Shuguang Li ◽  
Qiao Xiong ◽  
Hui Wang
Keyword(s):  
Differential Diagnosis ◽  
Retrospective Study ◽  
Pleural Effusion ◽  
Decision Tree ◽  
Pleural Fluid ◽  
Diagnostic Performance ◽  
Connective Tissue Diseases ◽  
Serum Lactate ◽  
Serum Lactate Dehydrogenase ◽  
Diagnostic Strategy

Abstract Purpose Pleural effusion (PE) is a common clinical manifestation, and millions of people suffer from pleural disease. Herein, this retrospective study was performed to evaluate the biomarkers and ratios in serum and pleural fluid (PF) for the differential diagnosis of the multiple types of PE and search for a new diagnostic strategy for PE. Methods In-patients, who developed tuberculous PE (TPE), malignant PE (MPE), complicated parapneumonic effusion (CPPE), uncomplicated PPE (UPPE), or PE caused by connective tissue diseases (CTDs) and underwent thoracentesis at Peking University People’s Hospital from November 2016 to April 2019, were included in this study. Eleven biomarkers and their ratios in serum and PF were investigated and compared between pairs of the different PE groups, and a decision-tree was developed. Results Totally 112 PE cases, including 25 MPE, 33 TPE, 19 CPPE, 27 UPPE, and 8 PE caused by CTDs, were reviewed. Biomarkers and ratios showed good diagnostic performance with high area under the curve values, sensitivities, and specificities for the differential diagnosis of the multiple types of PE. According to the decision-tree analysis, the combination of adenosine deaminase (ADA), serum albumin, serum lactate dehydrogenase, total protein, PF-LDH/ADA, and PF-LDH/TP provided the best predictive capacity with an overall accuracy of 84.8%; the sensitivity and specificity for TPE diagnosis were 100% and 98.7%, respectively. Conclusion The biomarkers and ratios showed good diagnostic performance, and a decision-tree with an overall accuracy of 84.8% was developed to differentiate the five types of PE in clinical settings.

scholarly journals Potential diagnostic value of pleural fluid cytokines levels for tuberculous pleural effusion

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Neda Dalil Roofchayee ◽  
Majid Marjani ◽  
Neda K. Dezfuli ◽  
Payam Tabarsi ◽  
Afshin Moniri ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Pleural Effusion ◽  
Diagnostic Accuracy ◽  
Pleural Fluid ◽  
Diagnostic Value ◽  
Parapneumonic Effusion ◽  
Pleural Effusions ◽  
Tuberculous Pleural Effusion ◽  
New Biomarkers ◽  
High Level

AbstractPatients with tuberculous pleural effusion (TPE) or malignant pleural effusions (MPE) frequently have similar pleural fluid profiles. New biomarkers for the differential diagnosis of TPE are required. We determined whether cytokine profiles in the PE of patients could aid the differential diagnosis of TPE. 30 patients with TPE, 30 patients with MPE, 14 patients with empyema (EMP) and 14 patients with parapneumonic effusion (PPE) were enrolled between Dec 2018 and 2019. The levels of interleukin (IL)-6, IL-18, IL-27, CXCL8, CCL-1 and IP-10 were determined in PE by ELISA along with measurements of adenosine deaminase (ADA). The best predictors of TPE were combined ADA.IL-27 [optimal cut-off value = 42.68 (103 U ng/l2), sensitivity 100%, specificity 98.28%], ADA [cut off value 27.5 (IU/l), sensitivity 90%, specificity 96.5%] and IL-27 [cut-off value = 2363 (pg/ml), sensitivity 96.7%, specificity 98.3%, p ≤ 0.0001]. A high level of IL-6 [cut-off value = 3260 (pg/ml), sensitivity 100%, specificity 67.2%], CXCL8 [cut-off value = 144.5 (pg/ml), sensitivity 93.3%, specificity 58.6%], CCL1 [cut-off value = 54 (pg/ml), sensitivity 100%, specificity 70.7%] and IP-10 [cut-off value = 891.9 (pg/ml), sensitivity 83.3%, specificity 48.3%] were also predictive of TPE. High ADA.IL-27, ADA and IL-27 levels differentiate between TPE and non-TPE with improved specificity and diagnostic accuracy and may be useful clinically.

scholarly journals Significance of secretory leukocyte peptidase inhibitor in pleural fluid for the diagnosis of benign asbestos pleural effusion

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takumi Kishimoto ◽  
Yoko Kojima ◽  
Nobukazu Fujimoto
Keyword(s):  
Pleural Effusion ◽  
Pleural Fluid ◽  
Early Stage ◽  
Area Under The Curve ◽  
Pleural Effusions ◽  
Tissue Destruction ◽  
Secretory Leukocyte Peptidase Inhibitor ◽  
Galectin 3 ◽  
Peptidase Inhibitor ◽  
Better Than

AbstractSecretory leukocyte peptidase inhibitor (SLPI) is a biomarker present in the respiratory tract that protects against tissue destruction and aids in wound healing. We examined whether SLPI in pleural effusion can be used to distinguish benign asbestos pleural effusion (BAPE) from early-stage malignant pleural mesothelioma (MPM) and other diseases. We measured the levels of SLPI, hyaluronic acid (HA), soluble mesothelin-related peptides (SMRP), CCL2, galectin-3, and CYFRA21-1 in 51 patients with BAPE, 37 patients with early-stage MPM, 77 patients with pleural effusions due to non-small-cell lung cancer (LCa), and 74 patients with other pleural effusions. SLPI levels in the pleural fluid of patients with BAPE were significantly lower than those in patients with MPM, LCa, and other pleural effusions (p < 0.0001). The area under the curve (AUC) for SLPI’s ability to distinguish BAPE from MPM was 0.902, with a sensitivity of 82.4% and a specificity of 86.5%. This AUC was not only favourable but was better than the AUC for the ability of CYFRA21-1 to distinguish BAPE (0.853). The combination of SLPI and CYFRA21-1 achieved an AUC of 0.965 for the differentiation between BAPE and MPM. Pleural fluid SLPI as well as CYFRA21-1 and HA is useful as a biomarker to diagnose BAPE, which needs to be distinguished from early-stage MPM.

Pleural Fluid Pseudouridine in Malignant and Benign Pleural Effusions

1998 ◽  
Vol 35 (1) ◽  
pp. 94-98 ◽  
Author(s):  
T W L Mak ◽  
S S Ho ◽  
C S Ho ◽  
M G Jones ◽  
C K W Lai ◽  
...  
Keyword(s):  
Pleural Effusion ◽  
Pleural Fluid ◽  
Roc Curve ◽  
Curve Analysis ◽  
Pleural Effusions ◽  
Clinical Value ◽  
Roc Curve Analysis ◽  
Malignant Pleural Effusions ◽  
Bonferroni Adjustment ◽  
Malignant Group

Pseudouridine in urine and plasma has been proved to be a useful tumour marker in many malignant conditions. We studied its usefulness in pleural fluid for distinguishing malignant from non-malignant pleural effusions. Pleural fluid pseudouridine concentrations in different groups of patients with pleural effusion (31 malignant, 29 benign, 16 unknown, 1 double pathology) was measured and compared. Its usefulness in distinguishing malignant from non-malignant pleural effusions was analysed by receiver-operating characteristic (ROC) curve analysis. Pseudouridine concentrations in the malignant group were significantly higher than the non-malignant group ( P < 0.017, Bonferroni adjustment) with values overlapping extensively at the lower end. The area-under-the curve (AUC) value in the ROC curve analysis was 0.675 ( P < 0.05). We conclude that the pleural fluid pseudouridine is of limited clinical value in distinguishing malignant from non-malignant pleural effusion due to its extensive overlap. However, it is useful when the concentration is higher than 65 μmol/L, which indicates malignancy.

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