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

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 > 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 < 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.

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

10.21203/rs.3.rs-66873/v1 ◽

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.

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

Scientific Reports ◽

10.1038/s41598-020-79685-1 ◽

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.

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Diagnostic efficacy and suitability of trans-thoracic ultrasonography for pleural fluid detection – The future non-invasive gold-standard?

Journal of Fatima Jinnah Medical University ◽

10.37018/jfjmu.558 ◽

2020 ◽

Vol 13 (4) ◽

pp. 184-190

Author(s):

Muhammad Irfan ◽

Abdul Rasheed Qureshi ◽

Zeeshan Ashraf ◽

Muhammad Amjad Ramzan ◽

Tehmina Naeem ◽

...

Keyword(s):

Pleural Effusion ◽

Diagnostic Accuracy ◽

Pleural Fluid ◽

Gold Standard ◽

Pleural Effusions ◽

Diagnostic Efficacy ◽

Chest Sonography ◽

X Ray ◽

Non Invasive ◽

Fluid Detection

ABSTRACT Background: Conventionally Pleural effusions are suspected by history of pleuritis, evaluated by physical signs and multiple view radiography. Trans-thoracic pleural aspiration is done and aspirated pleural fluid is considered the gold-standard for pleural effusion. Chest sonography has the advantage of having high diagnostic efficacy over radiography for the detection of pleural effusion. Furthermore, ultrasonography is free from radiation hazards, inexpensive, readily available and feasible for use in ICU, pregnant and pediatric patients. This study aims to explore the diagnostic accuracy of trans-thoracic ultrasonography for pleural fluid detection, which is free of such disadvantages. The objective is to determine the diagnostic efficacy of trans-thoracic ultrasound for detecting pleural effusion and also to assess its suitability for being a non-invasive gold-standard. Subject and Methods: This retrospective study of 4597 cases was conducted at pulmonology OPD-Gulab Devi Teaching Hospital, Lahore from November 2016 to July 2018. Adult patients with clinical features suggesting pleural effusions were included while those where no suspicion of pleural effusion, patients < 14 years and pregnant ladies were excluded. Patients were subjected to chest x-ray PA and Lateral views and chest ultrasonography was done by a senior qualified radiologist in OPD. Ultrasound-guided pleural aspiration was done in OPD & fluid was sent for analysis. At least 10ml aspirated fluid was considered as diagnostic for pleural effusion. Patient files containing history, physical examination, x-ray reports, ultrasound reports, pleural aspiration notes and informed consent were retrieved, reviewed and findings were recorded in the preformed proforma. Results were tabulated and conclusion was drawn by statistical analysis. Results: Out of 4597 cases, 4498 pleural effusion were manifested on CXR and only 2547(56.62%) pleural effusions were proved by ultrasound while 2050 (45.57%) cases were reported as no Pleural effusion. Chest sonography demonstrated sensitivity, specificity, PPV, NPV and diagnostic accuracy 100 % each. Conclusions: Trans-thoracic ultrasonography revealed an excellent efficacy that is why it can be considered as non-invasive gold standard for the detection of pleural effusion.

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The Differential Diagnostic Values of Cytokine Levels in Pleural Effusions

Mediators of Inflammation ◽

10.1155/mi.2005.2 ◽

2005 ◽

Vol 2005 (1) ◽

pp. 2-8 ◽

Cited By ~ 15

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.

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The Diagnostic Role of Sputum miRNA in Non-Small Cell Lung Cancer

10.21203/rs.3.rs-62275/v1 ◽

2020 ◽

Author(s):

Zaoxiu Hu ◽

Yonghe Zhao ◽

Yanlong Yang ◽

Zhenghai Shen ◽

Yunchao Huang

Keyword(s):

Lung Cancer ◽

Diagnostic Accuracy ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Early Stage ◽

Small Cell ◽

Stage I ◽

Small Cell Lung ◽

Diagnostic Role

Abstract Objective: Recent studies indicated sputum miRNAs may provide a promising approach for non-small cell lung cancer (NSCLC) diagnosis. But some results were still inconsistent. So, we performed meta-analysis to evaluate the diagnostic role of sputum miRNAs for the detection of NSCLC.Methods: Eligible studies that estimated the diagnostic accuracy of sputum miRNAs in NSCLC were searched in Pubmed, Embase and Web of Science and Chinese National Knowledge Infrastructure (CNKI). Data from the eligible studies were collected and pooled; sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratios, weighted symmetric summary ROC curve and the area under the curve (AUC) were calculated by bi-variate random effects model. The between-study heterogeneity was evaluated by Q test and I2 statistics.Results: 30 studies from 16 articles were included for analysis. The overall analysis yielded the sensitivity of 0.77 (95% CI: 0.73–0.81) and specificity of 0.87 (95% CI: 0.83–0.90), with an area under the SROC curve (AUC) of 0.89 (95% CI: 0.86–0.91). Subgroup analysis revealed the diagnostic accuracy in multiple miRNAs studies was higher than single miRNA (the sensitivity, specifcity and an AUC of multiple miRNAs were 0.76, 0.88 and 0.90; and for single miRNA, it was 0.74, 0.74, and 0.80). The diagnostic performance in early stage NSCLC was also very high (the sensitivity, specifcity and an AUC of stage I/II was 0.76, 0.88 and 0.91; and for stage I, it was 0.79, 0.85, and 0.87). We also found miR-210, miR-21, miR-31 and miR-126-3p might serve as potential biomarkers for lung cancer.Conclusion: Sputum miRNAs was useful noninvasive biomarkers for NSCLC diagnosis.

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