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Background: Early, rapid and precise diagnosis of tuberculous pleurisy is difficult. Next-generation sequencing (NGS) has been used for the diagnosis of TB in some high-income countries. We completed the protocol of the study in order to better guide the systematic review and meta-analysis for evaluating the role of NGS in the diagnosis of tuberculous pleurisy, which was the purpose of the current study., Methods: We designed and drafted this protocol as per the Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) guidelines. Three English databases (Cochrane Library, Embase and Medline via PubMed) and two Chinese databases (China National Knowledge Infrastructure and Wanfang Database) will be used to search for relevant studies. We followed the PICT principles to develop the eligibility criteria. Once the final compliant literature is identified, we will extract the valid information from the literature for statistical analysis. We will assess the quality of the included studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. When there are more than 4 eligible studies, we will use Stata (version 15.0; Stata Corp., College Station, TX, the USA) with midas module to conduct the relevant meta-analysis and plot the relevant forest plots and curves. When there are less than 4 eligible studies, we will use Meta-DiSc (version 1.4) to perform the associated meta-analysis and plot the associated forest plots and curves. We will use the I2 statistic to assess heterogeneity between included studies. We will conduct meta-regression analysis, subgroup analysis and sensitivity analysis to explore possible sources of heterogeneity when significant heterogeneity exists., Systematic Review Registration: PROSPERO Registration number: CRD42024568791., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Ling et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Tuberculous pleural effusion (TPE) is a challenging extrapulmonary manifestation of tuberculosis, with traditional diagnostic methods often involving invasive surgery and being time-consuming. While various machine learning and statistical models have been proposed for TPE diagnosis, these methods are typically limited by complexities in data processing and difficulties in feature integration. Therefore, this study aims to develop a diagnostic model for TPE using ChatGPT-4, a large language model (LLM), and compare its performance with traditional logistic regression and machine learning models. By highlighting the advantages of LLMs in handling complex clinical data, identifying interrelationships between features, and improving diagnostic accuracy, this study seeks to provide a more efficient and precise solution for the early diagnosis of TPE., Methods: We conducted a cross-sectional study, collecting clinical data from 109 TPE and 54 non-TPE patients for analysis, selecting 73 features from over 600 initial variables. The performance of the LLM was compared with logistic regression and machine learning models (k-Nearest Neighbors, Random Forest, Support Vector Machines) using metrics like area under the curve (AUC), F1 score, sensitivity, and specificity., Results: The LLM showed comparable performance to machine learning models, outperforming logistic regression in sensitivity, specificity, and overall diagnostic accuracy. Key features such as adenosine deaminase (ADA) levels and monocyte percentage were effectively integrated into the model. We also developed a Python package ( https://pypi.org/project/tpeai/ ) for rapid TPE diagnosis based on clinical data., Conclusions: The LLM-based model offers a non-surgical, accurate, and cost-effective method for early TPE diagnosis. The Python package provides a user-friendly tool for clinicians, with potential for broader use. Further validation in larger datasets is needed to optimize the model for clinical application., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Ethics Committee of the Affiliated Hospital of Jiujiang University (Approval No.: jjumer-b-2024-0405) and was conducted in accordance with the Declaration of Helsinki. As retrospective data were used, written informed consent was waived. This article does not include any research involving human participants by the authors. All data were analyzed anonymously to ensure the privacy of the participants. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Tuberculous pleural effusion (TPE) diagnosis still faces many difficulties and challenges. Some studies have shown that pleural interleukin -27 (IL-27) had a diagnostic potential for TPE. However, their findings are not always consistent. This study aimed to investigate the diagnostic accuracy of pleural IL-27 for TPE., Methods: We prospectively enrolled 211 patients with undiagnosed pleural effusion. Effusion Mycobacterium tuberculosis (Mtb) culture, Ziehl-Neelsen staining, biopsy, and response to antituberculosis therapy were used to define TPE. The pleural IL-27 levels were determined by enzyme-linked immunosorbent assay (ELISA). A receiver operating characteristic curve (ROC) with the area under the curve (AUC) was used to evaluate the diagnostic accuracy of IL-27 for TPE. In addition, we investigated the influence of age on the diagnostic performance of IL-27 by resampling patients with different upper age limits in the inclusion criteria., Results: Among the 211 enrolled participants, 33 were TPE and 178 were non-TPE. The mean concentration of IL-27 in TPE patients was significantly higher than that of non-TPE patients. The AUC of IL-27 was 0.76 (95 %CI: 0.67-0.86). At the threshold of 500 pg/mL, the sensitivity and specificity of IL-27 were 0.26 (95 %CI: 0.20-0.33) and 0.91 (95 %CI:0.76-0.97), respectively. The AUC of IL-27 is 0.84 in patients with an upper age limit of 70. Still, it decreased to 0.76 in patients with an upper age limit of 75., Conclusion: Age can affect the diagnostic performance of IL-27 for TPE., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Pleural tuberculoma is often observed during treatment for tuberculous pleurisy; however, this condition is rarely found as a solitary pleural nodule in patients without a history of tuberculosis treatment, and no cases have been reported in children. We report a case of a 12-year-old boy with pleural tuberculoma presenting as a solitary mass. He had a fever and cough that prompted chest radiography, which revealed a mass in the right lung. Symptoms improved with antibacterial medication; however, computed tomography (CT) revealed a 4.5-cm pleural mass that partially bordered the ribs. CT-guided biopsy revealed a necrotizing granuloma, but the real-time polymerase chain reaction result for Mycobacterium tuberculosis was negative. Malignant diseases, such as osteosarcoma, could not be ruled out; thus, surgical resection was performed, and pleural tuberculoma was diagnosed. The patient was treated with antituberculosis drugs for 6 months, and no recurrence was observed in the following 2 years. Pleural tuberculomas should be considered in the differential diagnosis of solitary pleural tumors, especially in countries where tuberculosis is endemic., (Copyright © 2025 by the American Academy of Pediatrics.)

Aim: Diagnosis of pleural tuberculosis (TB) is challenging; thus, an efficient method is urgently needed., Methods: We developed a magnetic-bead-gold nanoparticle-PCR amplified immunoassay (MB-AuNP-I-PCR, liquid system) to detect the Mycobacterium tuberculosis MPT-64 protein in pleural TB patients. AuNPs functionalized with detection antibodies/oligonucleotides were characterized by UV-vis spectroscopy, Transmission/Scanning electron microscopy, Fourier-transform infrared spectrometer, ELISA, and PCR, whereas MBs conjugated with detection antibodies were validated by magneto-ELISA/UV-vis spectroscopy., Results: We utilized the MB-AuNP-I-PCR for MPT-64 detection in 99 clinical specimens which displayed 85.2% sensitivity and 97.8% specificity to diagnose pleural TB cases. Markedly, the sensitivity achieved by MB-AuNP-I-PCR was noticeably higher ( p  < 0.01) than magneto-ELISA and GeneXpert., Conclusion: This is a preliminary report to diagnose pleural TB cases by MB-AuNP-I-PCR with promising results that require further corroboration in a higher number of specimens.

Extracellular vesicles (EVs) have recently emerged as a source of microbe-specific biomarkers for disease diagnosis. In the present study, we evaluated the utility of pleural fluid-derived extracellular vesicles (pEVs) as a source of Mycobacterium tuberculosis (M. tb.) antigens for pleural TB (pTB) diagnosis. EVs were isolated from pleural fluid (PF) samples and were characterized by scanning electron microscopy, and immunoblotting by targeting CD63 and LAMP2 markers. Antigen-detection ELISAs were developed for 2 M.tb.-specific antigens, MPT51 and MPT64 in pEVs (pEV-ELISA) and direct PF samples (PF-ELISA), and were evaluated on n = 86 samples in a blinded manner. Cut-off values were calculated by ROC-curve analysis to achieve 90 % (95%CI:73.47-97.89) and 86.67 % (95%CI:69.28-96.24) specificity for MPT51 and MPT64 pEV-ELISA respectively. The sensitivity of pEV-ELISA was 71.43 % (95%CI; 29.04-96.33) for MPT51 antigen and 57.14 % (95%CI; 18.41-90.1) for MPT64 antigen in the 'Definite' pTB group, while in the 'Definite and Probable' pTB group, the sensitivity was 62.86 % (95%CI:44.92-78.53) for MPT51 and 65.71 % (95%CI:47.79-80.87) for MPT64. The performance of PF-ELISA was sub-optimal, with 28.57 % (95%CI:3.67-70.96) and 14.29 % (95%CI:0.36-57.87) sensitivity for MPT51 and MPT64 in 'Definite' pTB group respectively. We conclude that M. tb.-antigens are concentrated in the EV-fraction of PF samples and EVs can be utilized for antigen-detection assays for pTB diagnosis., Competing Interests: Declaration of competing interest No competing interests are reported., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Medical thoracoscopy (MT) has gained widespread acceptance in the diagnosis of undiagnosed exudative pleural effusions. In developing countries, including India medical thoracoscopy is not widely available., Aims: 1. To analyze the yield of closed pleural biopsy (CPB) in comparison with MT in the diagnosis of undiagnosed exudative pleural effusions. 2. Comparison of complications between CPB and MT., Methodology: This was a prospective randomized controlled study conducted in a tertiary care centre, from January 2020 to September 2021. The patients with undiagnosed exudative pleural effusions were included in the study. The enrolled patients were randomized into two groups, group A and group B. Total of 38 patients were taken, 19 patients in each group. Group A was subjected to MT. Group B was subjected to CPB with cope's needle. Ultrasound was used to mark the site of pleural effusion., Results: Diagnostic yield was 78.9% in both MT and CPB group. CPB was significantly less painful procedure compared to MT. The duration of hospital stay was also significantly less in CPB as compared to MT (P < 0.001). CPB was associated with 5.3% mortality and there was no mortality in MT group., Conclusions: Our study recommends that, in the era of medical thoracoscopy, closed pleural biopsy still holds a significant role in the diagnosis of undiagnosed exudative pleural effusions especially where prevalence of tuberculosis is high. It is also a cost effective approach in developing countries like India., Competing Interests: Conflicts of interest The authors have none to declare., (Copyright © 2023 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Background: Pleural tuberculosis (pTB) is a diagnostic challenge because of its non-specific clinical features, lack of accurate diagnostic tools and paucibacillary nature of the disease. Methods: We, here describe the development of a novel magnetic nanoparticle antibody-conjugate and aptamer-based assay (MNp-Ab-Ap assay) targeting 4 different Mycobacterium tuberculosis ( M . tb. ) antigens (GlcB, MPT51, MPT64 and CFP-10) for pTB diagnosis. The MNp-Ab-Ap assay was developed by conjugating polyclonal antibodies on the surface of magnetic nanoparticles (MNPs) by using EDC-NHS chemistry. These conjugated MNPs were used to capture M. tb. antigens present in the pleural fluid samples. The resulting antigen-antibody complex was detected by antigen-specific 5'-biotinylated aptamers. All assays were standardized using samples of the 'Development set' (n=17) and evaluated in the 'Validation set' (n=114) in a blinded manner. Patient categorization was done using a 'Composite Reference Standard'. Assay cut-offs were determined from the 'Development set' (n=17; 'Definite & Probable' pTB; n=9 and 'Non-TB'; n=8) by calculating mean+3SD of OD 450 values of the 'Non-TB' group and applied to 'Validation set' (n=114; 'Definite' pTB; n=8, 'Probable' pTB; n=34, 'Possible' pTB; n=28 and 'Non-TB'; n=44). Results: Out of the 4 assays, MPT51-based MNp-Ab-Ap assay performed the best with 66.6% (95%CI;50.4-80.4) sensitivity and 95.4% (95%CI;85.1-99.4) specificity in the combined 'Definite and Probable' pTB group. Xpert MTB/RIF assay detected only six samples in the 'Validation set'. Binary logistic regression analysis indicated that MPT51-based MNp-Ab-Ap assay provided an incremental advantage over the existing diagnostic algorithm for pTB. Conclusions: We conclude that MPT51-based MNp-Ab-Ap assay is a novel technique that can pave the way towards rapid and accurate diagnosis of pTB., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Differentiating between tuberculosis and malignancy as the cause of an exudative lymphocyte predominant pleural effusion is difficult due to similarities in the cellular and biochemical characteristics of the pleural fluid in both conditions. Microbiological tests in tubercular pleural effusions have a poor diagnostic yield, and the long turnaround time for results prevents an early diagnosis. The diagnosis of malignant pleural effusion (MPE) is hampered by a variable yield of pleural fluid cytology and closed pleural biopsy and the fact that thoracoscopy may not be readily available or feasible in each patient. A key gap in the existing knowledge is the performance of the serum lactate dehydrogenase to pleural adenosine deaminase ratio (ie, "cancer ratio"; CR) in differentiating between tuberculous and MPE in a high tuberculosis prevalence country like India, although its use has been well established in Western literature. The CR may find a practical application in the community health care settings in low-income countries without ready access to biopsy., Objective: This study aimed to evaluate the CR as a test to differentiate tubercular and malignant etiology in patients with an exudative lymphocyte predominant pleural effusion. Secondary objectives to be assessed include a comparison of CR to pleural fluid carcinoembryonic antigen in MPE and the association of histologic type of lung carcinoma to the CR positivity., Methods: This hospital-based, prospective, observational study will include patients admitted with pleural effusion whose pleural fluid reports indicate a lymphocyte-predominant exudate. The ability of the CR to discriminate between tuberculous and MPE will be evaluated as a primary objective of this study. The performance of CR and pleural fluid carcinoembryonic antigen in the diagnosis of MPE will be compared using the receiver operating characteristics and area under the curve for both tests as a secondary objective. The association between a positive CR and histologic type of lung cancer will be analyzed as well., Results: Data collection began in June 2022. As of March 24, 2024, we have recruited 22 patients. Outcomes of the study are expected at the end of 2024., Conclusions: The results of this study will provide an objective basis for the use of CR in differentiating between tuberculosis and malignancy as the cause of an exudative lymphocyte predominant pleural effusion., International Registered Report Identifier (irrid): DERR1-10.2196/56592., (©Sai Pooja Chalamalasetty, Preetam Acharya, Thomas Antony, Anand Ramakrishna, Himani Kotian. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 23.12.2024.)

BACKGROUNDCurrent diagnostic tools for tuberculous pleural effusion (TPE) are often inadequate, making accurate diagnosis challenging. Effective identification of TPE is critical for ensuring proper treatment and preventing tuberculosis relapse. This study explored the potential of granzyme A (GZMA) as a biomarker for TPE.METHODSPatients with TPE, malignant pleural effusion (MPE), and parapneumonic pleural effusion (PPE) were recruited into discovery and validation cohorts. The discovery cohort consisted of 200 patients with TPE and 100 patients with MPE, while the validation cohort included 167 patients with TPE, 84 patients with MPE, and 69 patients with PPE.RESULTSIn the discovery cohort, GZMA levels were significantly elevated in TPE compared with MPE, demonstrating 90% sensitivity and 91% specificity at a cutoff of 102.29 ng/mL for effectively distinguishing between the two conditions. In the validation cohort, GZMA maintained high diagnostic performance, distinguishing TPE from MPE with 87% sensitivity and 87% specificity and from PPE with 87% sensitivity and 84% specificity. Incorporating GZMA, lactate dehydrogenase (LDH), and adenosine deaminase (ADA) into a random forest model further improved diagnostic accuracy. In the discovery cohort, this model achieved 92% sensitivity and 100% specificity, and in the validation cohort, it distinguished TPE from MPE with 87% sensitivity and 94% specificity and from PPE with 87% sensitivity and 91% specificity.CONCLUSIONOverall, GZMA is a promising biomarker for diagnosing TPE, with improved accuracy when combined with LDH and ADA, providing a robust tool for timely identification and effective management of patients with TPE.FUNDINGThe study was supported by Science and Technology Project of Shenzhen (KCXFZ20211020163545004, KQTD20210811090219022, JCYJ20220818095610021, JSGG20220822095200001, JCYJ20210324094614038), Shenzhen Medical Research Funding (B2302035, A2302004), Provincial Natural Science Foundation of Guangdong (2022A1515220034), and Shenzhen Third People's Hospital Research Foundation (G2022155).

Background: Previous studies indicated that pleural fluid complement C1q was helpful for diagnosing tuberculous pleural effusion (TPE), but the participants in these studies were young. The diagnostic accuracy of C1q for TPE in elderly patients remains unknown. This study aimed to investigate the diagnostic accuracy of C1q for TPE in elderly patients., Methods: We prospectively recruited patients with undiagnosed pleural effusion who visited the Affiliated Hospital of Inner Mongolia Medical University between September 2018 and July 2021. Their C1q in pleural fluid was detected, and the diagnostic accuracy of C1q was assessed by the receiver operating characteristic (ROC) curve analysis., Results: The median ages of patients with TPE and non-TPE were 75 and 71 years, respectively. TPE patients had significantly higher C1q than non-TPE. The area under the ROC curve (AUC) of C1q was 0.67 (95 %CI: 0.51-0.82). At the threshold of 100 mg/L, C1q had a sensitivity of 0.44 (95 %CI: 0.19-0.69) and specificity of 0.79 (95 %CI: 0.71-0.86)., Conclusion: C1q in pleural fluid has low diagnostic accuracy for TPE in elderly patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A 6-year-old boy was referred with complaints of chest pain for 2 months with low-grade fever. A computerized tomography of the chest revealed a loculated pleural effusion on the left side. Medical thoracoscopy was performed that revealed a characteristic sago-grain follicle over the parietal pleural. Histopathology and microbiological investigations on pleural biopsy samples confirmed tubercular pleural effusion., (© 2024 Wiley Periodicals LLC.)

Background: Simple, rapid, and accurate diagnosis of tuberculous pleural effusion (TPE) remains challenging. This study aimed to determine the accuracy of IFN-γ in diagnosing TPE., Methods: We quantified the expression of interferon-gamma (IFN-γ) in blood (B), adenosine deaminase (ADA), and IFN-γ in pleural effusions (PE) from 25 TPE patients and 31 non-TPE patients using a combination of immunological assays and flow cytometric analysis. The diagnostic performance of these three biomarkers was evaluated using receiver operating characteristic (ROC) curves., Results: We found that IFN-γ levels in blood and pleural fluid were higher in the TPE group than in the non-TPE group. The mean concentration of IFN-γ in pleural fluid of the TPE group was 3140.90 (1817.94, 6611.05) pg/mL, while that of the non-TPE group was 4.91 (0.69, 8.6) pg/mL), and the difference was statistically significant (z = 6.39, P < 0.001). The mean blood IFN-γ was 40.19 (16.45, 59.08) pg/mL in the TPE group and 2.76 (1.96, 6.02) pg/mL in the non-TPE group, which was statistically different (z = 5.12, P < 0.001). The area under the ROC curve (AUC) for pleural fluid IFN-γ, blood IFN-γ, and ADA were 0.999 (95 % CI: 0.994-1.00), 0.901 (95 % CI: 0.798-1.00) and 0.996 (95 % CI: 0.987-1.00), respectively., Conclusion: This study confirms that IFN-γ has high diagnostic validity in patients with TPE and can potentially be an excellent biomarker., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Tuberculosis (TB) is a leading cause of death worldwide from a single infectious agent. In China the most common extra-pulmonary TB (EPTB) is pleural tuberculosis (PLTB). An important clinical feature of PLTB is that the lymphocytes associated with TB will accumulate in the pleural fluid. The adaptive immune repertoires play important roles in Mycobacterium tuberculosis (Mtb) infection., Methods: In this study, 10 PLTB patients were enrolled, and their Peripheral Blood Mononuclear Cells(PBMCs) and Pleural Effusion Mononuclear Cells(PEMCs) were collected. After T cells were purified from PBMCs and PEMCs, high-throughput immunosequencing of the TCRβ chain (TRB), TCRγ chain(TRG), and B cell receptor(BCR) immunoglobulin heavy chain (IGH) were conducted on these samples., Results: The TRB, TRG, and BCR IGH repertoires were characterized between the pleural effusion and blood in PLTB patients, and the shared clones were analyzed and collected. The binding activity of antibodies in plasma and pleural effusion to Mtb antigens was tested which indicates that different antibodies responses to Mtb antigens in plasma and pleural effusion in PLTB patients. Moreover, GLIPH2 was used to identify the specificity groups of TRB clusters and Mtb-specific TRB sequences were analyzed and collected by VJ mapping., Conclusion: We characterize the adaptive immune repertoires and identify the shared clones and Mtb-specific clones in pleural effusion and blood in PLTB patients which can give important clues for TB diagnosis, treatment, and vaccine development., Competing Interests: Authors YD, LD and TS were employed by company Hangzhou ImmuQuad Biotechnologies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Du, Deng, Deng, Du, Xing, Tao, Li, Xie, Zhang, Sun and Li.)

This study examines the diagnostic utility of the combined interleukin-33 (IL-33), interferon-γ (IFN-γ), and interleukin-35 (IL-35) test in tuberculous pleural effusion. Forty patients with pleural effusion of unknown etiology admitted to the hospital between December 2020 and December 2023 were selected as the study group. The patients were further categorized into tuberculous (TB) (n = 20) and malignant (n = 20) groups on the basis of their relevant data, while sera from 20 healthy medical checkups were used as control group. Thoracentesis was used to collect pleural fluid, and after its collection, enzyme-linked immunosorbent assay was utilized to detect the concentration content of IL-35, IL-33, and IFN-γ in pleural fluid of patients with different types of diseases. Data processing and analysis were executed through SPSS23.0 software to plot the receiver operating characteristic curve and compare the area of the area under the line of each index. Adenosine deaminase level was statistically higher in TB group patients (59.91 U/L) than in malignant group (14.31 U/L) (P < .05). Pleural fluid lactate dehydrogenase levels did not differ significantly between the 2 groups (P > .05). T-SPOT test had a higher positive rate in the TB group (85%) and a lower positive rate in the malignant group (45%). The TB group exhibited significantly higher levels of IFN-γ expression than the malignant group (P < .05). The TB group had higher levels of IL-33 and IL-35 compared to the malignant group, with a statistically significant difference (P < .05). The TB group had a greater level of IL-33 (81.05 ± 10.11 pg/mL) than the cytology-positive group (39.37 ± 9.63 pg/mL), while the difference was not statistically significant (P > .05). The level of IL-35 (70.11 ± 10.37 pg/mL) in the TB group was lower than the level of IL-35 (72.13 ± 9.58 pg/mL) in the cytology-positive group. The specificity of the series of combined tests reached 95.81%, which was statistically superior to the single-factor test (P < .05). In the TB group, IFN-γ and IL-33, IFN-γ and IL-35, and IL-33 and IL-35 showed positive correlation. Combined determination of the concentration levels of IL-35, IL-33, and IFN-γ is of value in the diagnosis of tuberculous pleurisy., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Despite the advent of Xpert MTB/RIF, pleural tuberculosis (TB) diagnosis in pleural fluid is still difficult. Hence, we assessed the diagnostic efficacy of its advanced version, Xpert MTB/RIF Ultra, for pleural TB diagnosis using pleural fluid as a sample. Tuberculosis pleuritis (TBP) suspects (n = 261) were enrolled in the study, of which 29 were excluded. The remaining patients (n = 232) were categorized into definite TBP (n = 31), probable TBP (n = 28), and non-TB controls (n = 173) based on the composite reference standard consisting of smear, culture, histopathology, and Xpert MTB/RIF as well as follow-up/clinical response to anti-TB therapy. Among the TBP suspects, 59 were diagnosed as TBP patients. The sensitivity of Xpert MTB/RIF Ultra (52.5%) using pleural fluid for TBP diagnosis was higher than sensitivity obtained with smear (22.4%), culture (17.6%), and Xpert MTB/RIF (25%) alone, carried out using either pleural fluid or pleural biopsy or both the samples. In cases of probable TBP, where none of the laboratory tests were positive, Xpert MTB/RIF Ultra use led to an increased diagnostic percentage of definite TBP from 52.5% to 69.4%. Overall, Xpert MTB/RIF Ultra showed promising results for a definitive diagnosis of TBP in pleural fluid samples., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

Pleural infection leading to empyema is a severe condition marked by accumulated infected fluid in the pleural space. Pneumonia with parapneumonic effusion is its most common precursor. The global incidence of pleural infections has increased significantly, with existing literature mainly focusing on bacterial empyema, leaving a gap in comparative analyses.A retrospective review was conducted on 561 cases of bacterial, tuberculous, and fungal empyema over a 10-year period. The study compared and analysed overall survival rates, 30-day mortality rates after surgery, and clinical characteristics.The three empyema groups displayed distinct clinical characteristics. Fungal empyema had the worst overall survival compared to bacterial and tuberculous empyema, which had similar survival rates based on 30-day and 2-year mortality. Fungal empyema, advanced age, and high Charlson Comorbidity Index (CCI) score were independent predictors of poor prognosis.Fungal empyema has the highest mortality rate post-decortication surgery. Advanced age and high CCI score are independent predictors of poor prognosis..

Introduction: Adenosine deaminase (ADA) in pleural fluid is a useful marker for diagnosing tuberculous pleurisy. However, recent studies have reported a lower specificity of pleural fluid ADA levels. We previously developed a diagnostic flowchart for patients with pleural fluid ADA ≥40 U/L, incorporating variables such as pleural fluid lactate dehydrogenase <825 U/L, predominant pleural fluid neutrophils or cell degeneration, and a pleural fluid ADA/total protein ratio <14. This flowchart was effective in distinguishing between tuberculous pleurisy and other diseases. Here, we conducted a validation analysis of this flowchart., Materials and Methods: We retrospectively collected data from 458 patients with pleural fluid ADA concentrations ≥40 U/L across eight institutions from January 2019 to December 2023. The diagnostic accuracy rate, sensitivity, and specificity of the diagnostic flowchart were analysed and compared to those in the original study., Results: Eighty-seven patients were diagnosed with tuberculous pleurisy, and 371 patients were diagnosed with other diseases. The diagnostic accuracy, sensitivity, and specificity for diagnosing tuberculous pleurisy were 77.7%, 86.2%, and 75.7%, respectively. Compared with that in the original study, the rate of tuberculous pleurisy was lower (19.0% vs. 44.5%, p < 0.001), but the diagnostic accuracy rates were not significantly different (p = 0.253). On the basis of the findings from this validation study, we have revised the flowchart to enhance its utility., Conclusion: The diagnostic flowchart exhibited high diagnostic accuracy in this validation study, comparable to that in the original study. This validation confirms the effectiveness of the flowchart, even in settings with a low incidence of tuberculosis., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: There is substantial evidence indicating that cytokines play a role in the immune defense against tuberculosis. This study aims to evaluate the levels of various cytokines in pleural effusion to ditinguish between tuberculosis pleurisy and malignant pleurisy., Methods: A total of 82 participants with pleural effusion were included in the training cohort, and 76 participants were included in the validation cohort. The individuals were divided into tuberculosis and malignant pleurisy groups. The concentrations of interleukin-1β (IL-1β), IL-4, IL-6, IL-10, IL-17 A, IL-17 F, IL-21, IL-22, IL-25, IL-31, IL-33, interferon-γ (IFN-γ), soluble CD40 ligand (sCD40L) and tumor necrosis factor-α (TNF-α) in pleural effusion were measured using a multiplex cytokine assay. The threshold values were calculated according to the receiver operating characteristic (ROC) curve analysis to aid in diagnosing tuberculosis pleurisy. Furthermore, the combined measure was validated in the validation cohort., Results: The levels of all 14 cytokines in pleural effusion were significantly higher in participants with tuberculosis compared to those with malignant pleurisy (all P < 0.05). The area under the curve (AUC) was ≥ 0.920 for the IL-22, sCD40L, IFN-γ, TNF-α and IL-31, which were significantly increased in tuberculous pleural effusion (TPE) compared to MPE in the training cohort. Threshold values of 95.80 pg/mL for IFN-γ, 41.80 pg/mL for IL-31, and 18.87 pg/mL for IL-22 provided ≥ 90% sensitivity and specificity in distinguishing between tuberculosis pleurisy and malignant pleurisy in the training cohort. Among these, IL-22 combined with sCD40L showed the best sensitivity and specificity (94.0% and 96.9%) for diagnosing tuberculosis pleurisy, and this finding was validated in the validation cohort., Conclusion: We demonstrated that the levels of IL-1β, IL-4, IL-6, IL-10, IL-17 A, IL-17 F, IL-21, IL-22, IL-25, IL-31, IL-33, IFN-γ, sCD40L and TNF-α in pleural effusion had significant difference between tuberculosis pleurisy and malignant pleurisy. Specifically, IL-22 ≥ 18.87 pg/mL and sCD40L ≥ 53.08 pg/mL can be clinically utilized as an efficient diagnostic strategy for distinguishing tuberculosis pleurisy from malignant pleurisy., (© 2024. The Author(s).)

Background: China is experiencing rapid growth in its population of older adults, which may lead to increased susceptibility to tuberculous pleural effusion (TPE) due to age-related changes in the immune system. This study aimed to investigate the diagnostic potential of multiple biomarkers in individuals aged 60 years and above with pleural effusion., Methods: A total of 519 adult patients from Ningbo First Hospital were included in the study, with 7 biomarkers and their ratios in serum and pleural effusion analyzed using logistic regression analysis. Effusion Adenosine Deaminase(ADA), γ-Interferon Release Assay(IGRA), and Effusion lactatedehy drogenase(LDH)/Effusion ADA were identified as valuable parameters for differentiating TPE from non-TPE, particularly in individuals aged 60 years and older., Results: Effusion ADA, IGRA, and Effusion LDH/Effusion ADA were identified as valuable parameters for the differential diagnosis of TPE from non-TPE, showing good diagnostic performance in individuals aged 60 years and older. The combined diagnosis of these three indexes achieved the highest diagnostic accuracy for TPE in this age group, with an AUC of 0.925, sensitivity of 85.23%, and specificity of 89.57%., Conclusions: Overall, the study highlights the importance of using multiple indicators for a combined diagnosis to improve diagnostic efficacy in detecting tuberculous pleurisy in older individuals as for young patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Guo, Huimin, Xia, Xu, Jin and Liu.)

Aim: Tuberculosis (TB) came back in the top of causes for infectious disease-related deaths and its pleural involvement is still in the top two extrapulmonary sites. The authors continued their studies on TB pleural effusions (Pl-Effs) with the assessment of biological and cytological variable of pleural fluid (PF), introducing in the investigation algorithm and testing a new tool, the computer-assisted evaluation of cell populations on PF smears., Patients, Materials and Methods: A series of 85 patients with TB pleurisy (PLTB) were selected from a larger group of 322 patients with different types of Pl-Effs. The algorithm of investigation included. clinical variables, biological assays of PF, gross aspects including imagistic variables and PF cytology on May-Grünwald-Giemsa (MGG)-stained smears. All the data obtained were entered into and processed using Microsoft Excel module of the 2019 Microsoft Office Professional software along with the 2014 XLSTAT add-in program for MS Excel. The PF cellularity was assessed qualitatively by a cytologist and quantitatively with in-house software. Continuous variables were compared using Pearson's correlation test, while categorical variables were compared using χ² (chi-squared) test., Results: Our analysis showed that patients were usually males, aged between 25 and 44 years with Pl-Eff discovered at clinical imagistic examination, almost always one-sided and free in the pleural cavity. Its extension was either moderate or reduced. The PF had a serous citrine appearance in most of the cases, and biological characteristics pleaded for an exudate [high levels of proteins and lactate dehydrogenase (LDH)], with elevated adenosine deaminase (ADA) values and rich in lymphocytes (Ly). The attempt to identify the pathogen in PF was not of much help. Apart from Ly, neutrophils [polymorphonuclear neutrophils (PMNs)] were a rare presence and their amount had only a trend of direct correlation with Ly. The same situation was encountered in the case of mesothelial cells (MCs). The comparison between the qualitative and the quantitative, computer-assisted evaluations of cytological smears showed that the results of the two methods overlapped in less than one third of the cases, although the sensitivity and specificity values as well as the two calculated predictive values of the qualitative method were encouraging., Conclusions: The assessment of biological variables and cell populations of the PF are basic tools in the diagnosis of pleural TB. The assessment of PF cell population could be improved by the use of computer-assisted quantitative analysis of the PF smears, which is simple to design, easy to introduce and handle and reliable., Competing Interests: The authors declare that they have no conflict of interests.

Background: Tubercular Pleural effusion (TBPE) is one of most common extrapulmonary tuberculosis. It can be difficult to diagnose due to low sensitivity of pleural fluid smear, culture and CBNAAT. Diagnosis of TBPE is then dependent on the level of pleural fluid Adenosine Deaminase (ADA). Thoracoscopic pleural biopsy gives definite diagnosis specially in Low Pleural fluid ADA setting., Aims and Objective: This study was planned to find out the prevalence of tubercular etiology in patients of exudative pleural effusion with low ADA (ADA <40 IU/L)., Material and Methods: A Prospective, observational study was carried out in a tertiary teaching institute in north India. Total 142 patients of pleural effusion with low ADA were enrolled. All patients underwent rigid thoracoscopy for confirmation of their diagnosis., Results: Out of 142 patients, male were 78 (55%) and female were 64 (45%). Mean age of patients were 57.4 years. Tuberculosis was diagnosed as a cause of effusion in 22 (15.5%) out of 142 patients. Majority of TBPE patients had pleural thickening as thoracoscopic finding. Mean ADA level in TBPE was 27.36 ± 11.6 as compared to 18.55 ± 9.02 in non tubercular pleural effusion patients and this difference was significant statistically (P- 0.002)., Conclusion: The diagnosis of patients having exudative, low ADA pleural effusion can be very easily confirmed by thoracoscopy guided pleural biopsy which has a very high diagnostic yield., Competing Interests: Conflicts of interest The authors have none to declare., (Copyright © 2023 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Background: Tuberculous pleurisy (TP) is one of the most common types of extrapulmonary tuberculosis, often secondary to tuberculosis (TB). Clinical and imaging manifestations of non-tuberculous mycobacterial pulmonary diseases (NTM-PD) are usually similar to those of tuberculosis. Because of their similarity and the high incidence of tuberculosis, non-tuberculous mycobacterial infections are often overlooked for a long time. Especially in people without immunodeficiency., Methods: Mycobacterium tuberculosis (MTB) in pleural effusion was found by metagenomic next-generation sequencing (mNGS). During anti-tuberculosis treatment, mNGS of lung tissue by ultrasound-guided percutaneous lung puncture revealed that this patient had combined NTM-PD., Results: Mycobacterium chelonae (M. chelonae) was detected by mNGS, and after anti-NTM treatment, the patient's chest CT showed that the inflammation was absorbed more than before, and the patient's symptoms improved., Conclusions: When TB is poorly treated with standardized anti-tuberculosis therapy, comorbid non-tuberculous mycobacterial infections may be considered, and mNGS may complement traditional pathogenetic testing.

Background: Pleural effusion indicates an imbalance between pleural fluid formation and removal. Classified into exudative and transudative, with common symptoms of dry cough, dyspnea and pleuritic chest pain. Confirmed etiology has to be established for effective treatment., Objective: Correlate clinical and biochemical profile of various etiologies of pleural effusion., Materials & Methods: Retrospective observational study of 2 years in the department of respiratory medicine, GMC Bhopal on 280 cases of pleural effusion., Results: Most common etiology was tubercular 202 (72.4%) followed by malignant in 36 (12.8%). With respect to tubercular, malignant pleural effusion has relative risk (RR) of 0.138 (p value < 0.05) in the age group of 51-60 years, which is statistically significant. Patients of tuberculosis complained of fever 158 (78.2%) whereas with malignancy complained of chest pain 16 (44.4%) followed by hemoptysis 12 (33.3%). For hemoptysis, with respect to tubercular, malignant effusion has RR of 5.68 (p value < 0.05) which is significant. History of smoking was significant in malignant effusion with RR of 2.57 (p value < 0.05) as compared to tubercular. Pleural fluid ADA was >70 in 83.7% in tubercular effusion, glucose was <60 mg/dl in 79% tubercular, malignant and bacteriological cause, LDH was >1000 in 88.4% in bacteriological and 72.3% in malignant effusion., Conclusion: Lack of tools for confirming diagnosis leads to diagnostic dilemma and delay in treatment initiation, leading to deterioration and untoward fatality in some cases. Our goal is early diagnosis by correlating clinical symptoms with biochemical profile and help initiate rapid treatment., Competing Interests: Conflicts of interest The authors have none to declare., (Copyright © 2023 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

In a prospective cohort study, we evaluated plasma PCT levels in 48 TB lymphadenitis (TBLN) and 41 TB pleuritis (TBPE) patients. Measurements of PCT were done in unstimulated plasma of microbiologically and clinically confirmed TBLN and TBPE patients registered for anti-TB treatment at a tertiary care hospital in Lahore, Pakistan. Plasma levels of PCT were found to be raised in 89% of the patients at baseline with a median of 1.5 ng/ml. Levels were higher (p = 0.001) in TBLN as compared to TBPE (2.69, 0.96 ng/ml). PCT levels were not related to the bacterial burden depicted by culture positivity in these patients. PCT showed a negative correlation with the severity of constitutional symptoms (rho = - 0.238, p = 0.034), and inflammatory biomarkers; ferritin (rho = - 0.43, p < 0.001), INF-γ (rho = - 0.314, p = 0.003), TNF-α (rho = - 0.220, p = 0.039), IL-6 (rho = - 0.224, p = 0.035), and several chemokines of CCL and CCXL group. Raised plasma levels of PCT did not decrease with anti-TB treatment, indicating it is not a good biomarker to monitor treatment response in TBLN and TBPE patients. More studies with a larger number of confirmed EPTB cases are needed to define the role of PCT and its interaction with other biomarkers in EPTB., (© 2024. The Author(s).)

Objective: To investigate the expression and clinical significance of circular RNA (circRNA) 051778 in lung adenocarcinoma-malignant pleural effusion (LA-MPE) and tuberculous pleural effusion (TPE)., Methods: This is a cross-sectional study. A total of 212 patients were recruited from the Jiangxi Chest Hospital between October 2018 and September 2019, and their pleural effusion samples and/or plasma samples were collected. The exosomal circRNA profile was sketched by circRNA microarray. Differentially expressed circRNAs (DECs) were verified by droplet digital PCR. In addition, a putative circRNA-miRNA-mRNA network was constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to predict the functions of the DECs. The diagnostic value of circRNA&#95;051778 was evaluated by binary logistic regression and receiver operating characteristic curve., Results: The expression level of circRNA&#95;051778 in the LA-MPE samples was (3.92±0.48) copies/100 ng cDNA, while that in the TPE samples was (21.53±2.22) copies/100 ng cDNA. Compared to that in the TPE samples, circRNA&#95;051778 was significantly downregulated in the LA-MPE samples ( P <0.001). The potential targets of circRNA&#95;051778 were enriched in positive regulation of GTPase activity, cytoplasm, protein binding, and cancer-related pathways. The area under the curve (AUC) for the combined assessment of circRNA&#95;051778 with liquid-based thin-layer cytology (TCT), erythrocyte sedimentation rate (ESR), and tuberculosis antibody (TBA) was 0.98 (95% confidence interval: 0.97-1.00), with the sensitivity being 88.0% and the specificity being 100.0%., Conclusion: Exosomal circRNA&#95;051778 is downregulated in LA-MPE. According to the findings from the GO and KEGG analyses, exosomal circRNA&#95;051778 may play a role in cancer development and has the potential to serve as a marker for differential diagnostic of LA-MPE and TPE when it is used in combination with TCT, ESR, and TBA., Competing Interests: 利益冲突　 本文作者张林是本刊主编。该文在编辑评审过程中所有流程严格按照期刊政策进行，且未经其本人经手处理。除此之外，所有作者声明不存在利益冲突。, (© 2024《四川大学学报（医学版）》编辑部 版权所有Copyright ©2024 Editorial Office of Journal of Sichuan University (Medical Sciences).)

Objective: To understand and analyze the factors relating to patient and diagnostic delays among groups with tuberculous pleurisy (TP), and its spatiotemporal distribution in Zhejiang Province., Methods: Data of all tuberculous pleurisy patients were collected from the existing Tuberculosis Information Management System. A time interval of > 2 weeks between first symptom onset and visit to the designated hospital was considered a patient delay, and a time interval of > 2 weeks between the first visit and a confirmed TP diagnosis was considered a diagnostic delay. Univariate and multivariate logistic regression analyses were used to explore factors influencing patient and diagnostic delays in patients with TP. Spatial autocorrelation and spatiotemporal scan analyses were used to identify hot spots and risk clusters, respectively., Results: In total, 10,044 patients with TP were included. The median time and interquartile range for patients seeking medical care and diagnosis were 15 (7-30) and 1 (0-8) days, respectively. The results showed that people aged > 65 years, retirees, and residents of Jinhua, Lishui, and Quzhou were positively correlated with patient delay, whereas retreatment patients, houseworkers, unemployed people, and residents of Zhoushan or Ningbo were positively correlated with diagnostic delay. Additionally, high-risk clusters of patient delays were observed in the midwestern Zhejiang Province. The most likely clusters of TP diagnostic delays were found in southeast Zhejiang Province., Conclusion: In summary, patient delay of TP in Zhejiang province was shorter than for pulmonary tuberculosis in China, while the diagnostic delay had no difference. Age, city, occupation, and treatment history were related to both patient and diagnostic delays in TP. Interventions in central and western regions of Zhejiang Province should be initiated to improve the early detection of TP. Additionally, the allocation of health resources and accessibility of health services should be improved in the central and eastern regions of Zhejiang Province., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Luo, Zheng, Liu, Chen, Zhang, Wang, Wu, Ling, Zhou, Chen and Jiang.)

This is the first reported case of a pediatric patient with tuberculous pleurisy and glucose-6-phosphate dehydrogenase deficiency treated with contezolid concomitantly with other antituberculous drugs. The patient responded well to treatment, and no adverse events were observed. These findings suggest that contezolid may be a potential therapeutic option for tuberculous pleurisy in children and adolescents with glucose-6-phosphate dehydrogenase deficiency., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Tuberculous pleurisy is one of the most common types of extra-pulmonary tuberculosis, but the sensitivity of conventional mycobacterial culture (Culture) or Xpert MTB/RIF assay (Xpert) is not satisfying. This multicentre cohort study evaluated the accuracy of a new cell-free DNA droplet digital PCR assay (cf-ddPCR) for diagnosing tuberculous pleurisy., Methods: Patients with suspected tuberculosis (≥5 years of age) with pleural effusion were consecutively recruited from nine research sites across six provinces in China between September 2020 to May 2022. Culture, Xpert, Xpert MTB/RIF Ultra assay (Ultra), real-time PCR, and cf-ddPCR were performed simultaneously for all specimens., Results: A total of 321 participants were enrolled, and data from 281 (87.5%) participants were available, including 105 definite tuberculous pleurisy, 113 possible tuberculous pleurisy and 63 non-tuberculous pleurisy according to the composite reference standard. The sensitivity of cf-ddPCR was 90.5% (95/105, 95% CI, 82.8-95.1%) in the definite tuberculous pleurisy group, which was significantly higher than those of Culture (57.1%, 60/105, 95% CI, 47.1-66.6%, p < 0.001), Xpert (46.7%, 49/105, 95% CI, 37.0-56.6%, p < 0.001), Ultra (69.5%, 73/105, 95% CI, 59.7-77.9%, p < 0.001) and real-time PCR (75.2%, 79/105, 95% CI, 65.7-82.9%, p < 0.001). In possible tuberculous pleurisy, whose results of Culture and Xpert were both negative, the sensitivity of cf-ddPCR was 61.1% (69/113, 95% CI, 51.4-70.0%), which was still significantly higher than that of Ultra (27.4%, 31/113, 95% CI, 19.7-36.8%, p < 0.001) and real-time PCR (38.9%, 44/113, 95% CI, 30.0-48.6%, p < 0.001)., Discussion: The performance of cf-ddPCR is superior to Culture, Xpert, Ultra, and real-time PCR, indicating that improved diagnostic accuracy can be anticipated by incorporating this new assay., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: The diagnosis of tuberculous pleurisy (TP) presents a significant challenge due to the low bacterial load in pleural effusion (PE) samples. Cell-free Mycobacterium tuberculosis DNA (cf-TB) in PE samples is considered an optimal biomarker for diagnosing TP. This study aimed to evaluate the applicability of cf-TB testing across diverse research sites with a relatively large sample size., Methods: Patients suspected of TP and presenting with clinical symptoms and radiological evidence of PE were consecutively enrolled by treating physicians from 11 research sites across 6 provinces in China between April 2020 and August 2022. Following centrifugation, sediments obtained from PE were used for Xpert MTB/RIF (Xpert) and mycobacterial culture, while the supernatants were subjected to cf-TB testing. This study employed a composite reference standard to definite TP, which was characterized by any positive result for Mycobacterium tuberculosis (MTB) through either PE culture, PE Xpert, or pleural biopsy., Results: A total of 1412 participants underwent screening, and 1344 (95.2%) were subsequently enrolled in this study. Data from 1241 (92.3%) participants were included, comprising 284 with definite TP, 677 with clinically diagnosed TP, and 280 without TP. The sensitivity of cf-TB testing in definite TP was 73.6% (95% CI 68.2-78.4), significantly higher than both Xpert (40.8%, 95% CI 35.3-46.7, P < 0.001) and mycobacterial culture (54.2%, 95% CI 48.4-59.9, P < 0.001). When clinically diagnosed TP was incorporated into the composite reference standard for sensitivity analysis, cf-TB testing showed a sensitivity of 46.8% (450/961, 95% CI 43.7-50.0), significantly higher than both Xpert (116/961, 12.1%, 95% CI 10.2-14.3, P < 0.001) and mycobacterial culture (154/961, 16.0%, 95% CI 13.8-18.5, P < 0.001). The specificities of cf-TB testing, Xpert, and mycobacterial culture were all 100.0%., Conclusions: The performance of cf-TB testing is significantly superior to that of Xpert and mycobacterial culture methods, indicating that it can be considered as the primary diagnostic approach for improving TP detection. Trial registration The trial was registered on Chictr.org.cn (ChiCTR2000031680, https://www.chictr.org.cn/showproj.html?proj=49316 )., (© 2024. The Author(s).)

Background: The distinction between lung adenocarcinoma-associated malignant pleural effusion (MPE) and tuberculous pleural effusion (TPE) continues to pose a challenge. This study sought to assess the supplementary value of tumor markers in enabling a differential diagnosis., Methods: Data concerning tumor markers, which included carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), cancer antigen 153 (CA153), cancer antigen 724 (CA724), neuron-specific enolase (NSE), cytokeratin19 fragment (Cyfra21-1), and squamous cell carcinoma antigen (SCCA), in both serum and pleural effusion samples, were retrospectively compiled from lung adenocarcinoma-associated MPE and TPE patients. A comparative analysis of tumor marker concentrations between the two groups was performed to assess diagnostic utility, followed by a multiple logistic regression to control for confounding variables., Results: While gender, serum CA125 and SCCA, and pleural effusion SCCA manifested comparability between the groups, distinctions were noted in patient age and the concentration of other tumor markers in serum and pleural effusion, which were notably elevated in the MPE group. Multiple logistic regression demonstrated a positive association between the risk of lung adenocarcinoma-associated MPE and levels of CEA and CA153 in serum and pleural effusion, as well as Cyfra21-1 in serum (P < 0.05). The odds ratio for CEA surpassed that of CA153 and Cyfra21-1., Conclusions: CEA and CA153 in serum and pleural effusion, and Cyfra21-1 in serum emerge as biomarkers possessing supplementary diagnostic value in distinguishing lung adenocarcinoma-associated MPE from TPE. The diagnostic efficacy of CEA is superior to CA153 and Cyfra21-1. Conversely, the utility of CA125, CA724, NSE, and SCCA appears constrained., Competing Interests: Declaration of Competing Interests The author has no financial or other conflicts of interest to disclose., (Copyright © 2024 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Tuberculosis (TB) was the leading cause of death from a single infectious agent before the coronavirus pandemic. Therefore, it is important to search for severity biomarkers and devise appropriate therapies. A total of 139 pulmonary TB (PTB) patients and 80 healthy controls (HCs) were recruited for plasma soluble CD137 (sCD137) detection through ELISA. Moreover, pleural effusion sCD137 levels were measured in 85 TB patients and 36 untreated lung cancer patients. The plasma cytokine levels in 64 patients with PTB and blood immune cell subpopulations in 68 patients with PTB were analysed via flow cytometry. Blood sCD137 levels were higher in PTB patients (p = 0.012) and correlated with disease severity (p = 0.0056). The level of sCD137 in tuberculous pleurisy effusion (TPE) was markedly higher than that in malignant pleurisy effusion (p = 0.018). Several blood cytokines, such as IL-6 (p = 0.0147), IL-8 (p = 0.0477), IP-10 (p ≤ 0.0001) and MCP-1 (p = 0.0057), and some laboratory indices were significantly elevated in severe PTB (SE) patients, but the percentages of total lymphocytes (p = 0.002) and cytotoxic T cells (p = 0.036) were significantly lower in SE patients than in non-SE patients. In addition, the sCD137 level was negatively correlated with the percentage of total lymphocytes (p = 0.0008) and cytotoxic T cells (p = 0.0021), and PTB patients with higher plasma sCD137 levels had significantly shorter survival times (p = 0.0041). An increase in sCD137 is a potential biomarker for severe TB and indicates a poor prognosis., (© 2024 The Authors. European Journal of Immunology published by Wiley‐VCH GmbH.)

Pleurisy can be categorized as primary or secondary, arising from immunological, tumorous, or microbial conditions. It often results in lung structure damage and the development of various respiratory issues. Among the different types, tuberculous pleurisy has emerged as a prominent focus for both clinical and scientific investigations. The IL-10 family, known for its anti-inflammatory properties in the human immune system, is increasingly being studied for its involvement in the pathogenesis of pleurisy. This review aims to present a detailed overview of the intricate role of IL-10 family members (specifically IL-10, IL-22, and IL-26) in human and animal pleuritic diseases or relevant animal models. These insights could serve as valuable guidance and references for further studies on pleurisy and potential therapeutic strategies., (© 2024. The Author(s).)

Background and Objectives: Diagnosis of tuberculous pleurisy (TP) may be challenging and it often requires pleural biopsy. A tool able to increase pre-test probability of TP may be helpful to guide diagnostic work-up and enlargement of internal mammary lymph node (IMLN) has been suggested to play a potential role. The aim of the present investigation was to assess role of IMLN involvement in TP in a multi-centric case-control study, by comparing its prevalence and test performance to those observed in patients with infectious, non-tuberculous pleurisy (NTIP), and in controls free from respiratory diseases (CP)., Methods: A total of 419 patients, from 14 Pulmonology Units across Italy were enrolled (127 patients affected by TP, 163 affected by NTIP and 129 CP). Prevalence, accuracy and predictive values of ipsilateral IMLN involvement between cases and control groups were assessed, as well as concordance between chest computed tomography (CT scan) and thoracic ultrasound (TUS) measurements., Results: The prevalence of ipsilateral IMLN involvement in TP was significantly higher than that observed in NTIP and CP groups (respectively 77.2%, 39.3% and 14.7%). Results on test performance, stratified by age, revealed a high positive predictive value in patients aged ≤50 years, while a high negative predictive value in patients aged >50 years. The comparison between CT scan and ultrasound showed moderate agreement (Kappa=0.502)., Conclusions: Evaluation of IMLN involvement plays a relevant role in assessing the pre-test probability of TP. Considering the increasing global prevalence of mycobacterial infections, a tool able to guide diagnostic work-up of suspected TP is crucial, especially where local sources are limited., Competing Interests: Conflicts of interest None., (Copyright © 2022 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Tuberculous pleural effusion poses a significant threat to human health due to its potential for severe disease and mortality. Without timely treatment, it may lead to fatal consequences. Therefore, early identification and prompt treatment are crucial for preventing problems such as chronic lung disease, respiratory failure, and death. This study proposes an enhanced differential evolution algorithm based on colony predation and dispersed foraging strategies. A series of experiments conducted on the IEEE CEC 2017 competition dataset validated the global optimization capability of the method. Additionally, a binary version of the algorithm is introduced to assess the algorithm's ability to address feature selection problems. Comprehensive comparisons of the effectiveness of the proposed algorithm with 8 similar algorithms were conducted using public datasets with feature sizes ranging from 10 to 10,000. Experimental results demonstrate that the proposed method is an effective feature selection approach. Furthermore, a predictive model for tuberculous pleural effusion is established by integrating the proposed algorithm with support vector machines. The performance of the proposed model is validated using clinical records collected from 140 tuberculous pleural effusion patients, totaling 10,780 instances. Experimental results indicate that the proposed model can identify key correlated indicators such as pleural effusion adenosine deaminase, temperature, white blood cell count, and pleural effusion color, aiding in the clinical feature analysis of tuberculous pleural effusion and providing early warning for its treatment and prediction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: An ambitious plan was set into motion with the aim of TB elimination from India in 2025. To achieve this, it is high time to give emphasis on other prevalent forms of TB, such as extra pulmonary TB (EPTB)., Objectives: The study aims to discern the differences in patient characteristics and management practices between pulmonary TB and EPTB using data from district Ambala., Methods: This retrospective study used data of 12,985 TB patients from district Ambala, India. The differences in patient characteristics and management practices between pulmonary TB and EPTB were analyzed using the NIKSHAY database., Results: In the studied population, extra pulmonary TB (EPTB) formed 29.7% of all TB cases. Among all EPTB cases, pleural TB was found to be the most common form, accounting for 27%. The study also revealed that female gender, young age, non-diabetic status, and high BMI were associated with an increased propensity to have EPTB. Interestingly, unlike pulmonary TB, which had increased odds for contracting the disease in diabetic individuals (OR - 2.02), there were no increased odds for contracting EPTB in diabetic individuals. However, HIV infection significantly increased the odds for both pulmonary TB and EPTB. The results also showed diagnostic discrepancies between the private and public sectors, along with a low microbiological confirmation rate of 7.1% in EPTB cases., Conclusion: The study highlights the importance of focusing on EPTB in addition to pulmonary TB for effective TB elimination in India. The differences in patient characteristics and management practices warrant further investigation and targeted interventions for both forms of the disease. Efforts should be made to improve diagnostic accuracy and reduce discrepancies between the private and public sectors., Competing Interests: Conflict of interest The authors have none to declare., (Copyright © 2023 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Background: Pleural biomarkers represent potential diagnostic tools for tuberculous pleural effusion (TPE) due to their advantages of low cost, short turnaround time, and less invasiveness. This study evaluated the diagnostic accuracy of two CXCR3 ligands, C-X-C motif chemokine ligand 9 (CXCL9) and CXCL11, for TPE. In addition, we investigated the cellular origins and biological roles of CXCL9 and CXCL11 in the development of TPE., Methods: This double-blind study prospectively enrolled patients with undiagnosed pleural effusion from two centers (Hohhot and Changshu) in China. Pleural fluid on admission was obtained and levels of CXCL9 and CXCL11 were measured by an enzyme-linked immunosorbent assay (ELISA). The receiver operating characteristic (ROC) curve and the decision curve analysis (DCA) were used to evaluate their diagnostic accuracy and net benefit, respectively. THP-1 cell-derived macrophages were treated with Bacillus Calmette-Guérin (BCG), and quantitative real-time PCR (qRT-PCR) and ELISA were used to determine the mRNA and protein levels of CXCL9 and CXCL11. The chemoattractant activities of CXCL9 and CXCL11 for T helper (Th) cells were analyzed by a transwell assay., Results: One hundred and fifty-three (20 TPEs and 133 non-TPEs) patients were enrolled in the Hohhot Center, and 58 (13 TPEs and 45 non-TPEs) were enrolled in the Changshu Center. In both centers, we observed increased CXCL9 and CXCL11 in TPE patients. The areas under the ROC curves (AUCs) of pleural CXCL9 and CXCL11 in the Hohhot Center were 0.70 (95 % CI: 0.55-0.85) and 0.68 (95 % CI: 0.52-0.84), respectively. In the Changshu Center, the AUCs of CXCL9 and CXCL11 were 0.96 (95 % CI: 0.92-1.00) and 0.97 (95 % CI: 0.94-1.00), respectively. The AUCs of CXCL9 and CXCL11 decreased with the advancement of age. The decision curves of CXCL9 and CXCL11 showed net benefits in both centers. CXCL9 and CXCL11 were upregulated in BCG-treated macrophages. Pleural fluid from TPE and conditioned medium from BCG-treated macrophages were chemotactic for Th cells. Anti-CXCL9 or CXCL11 neutralizing antibodies could partly block the chemotactic activity., Conclusions: Pleural CXCL9 and CXCL11 are potential diagnostic markers for TPE, but their diagnostic accuracy is compromised in elderly patients. CXCL9 and CXCL11 can promote the migration of peripheral Th cells, thus representing a therapeutic target for the treatment of TPE., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: In this study, we examined the value of chest CT signs combined with peripheral blood eosinophil percentage in differentiating between pulmonary paragonimiasis and tuberculous pleurisy in children., Methods: Patients with pulmonary paragonimiasis and tuberculous pleurisy were retrospectively enrolled from January 2019 to April 2023 at the Kunming Third People's Hospital and Lincang People's Hospital. There were 69 patients with pulmonary paragonimiasis (paragonimiasis group) and 89 patients with tuberculous pleurisy (tuberculosis group). Clinical symptoms, chest CT imaging findings, and laboratory test results were analyzed. Using binary logistic regression, an imaging model of CT signs and a combined model of CT signs and eosinophils were developed to calculate and compare the differential diagnostic performance of the two models., Results: CT signs were used to establish the imaging model, and the receiver operating characteristic (ROC) curve was plotted. The area under the curve (AUC) was 0.856 (95% CI: 0.799-0.913), the sensitivity was 66.7%, and the specificity was 88.9%. The combined model was established using the CT signs and eosinophil percentage, and the ROC was plotted. The AUC curve was 0.950 (95% CI: 0.919-0.980), the sensitivity was 89.9%, and the specificity was 90.1%. The differential diagnostic efficiency of the combined model was higher than that of the imaging model, and the difference in AUC was statistically significant., Conclusion: The combined model has a higher differential diagnosis efficiency than the imaging model in the differentiation of pulmonary paragonimiasis and tuberculous pleurisy in children. The presence of a tunnel sign on chest CT, the absence of pulmonary nodules, and an elevated percentage of peripheral blood eosinophils are indicative of pulmonary paragonimiasis in children., (© 2024. The Author(s).)

Background: Pleural fluid is one of the common complications of thoracic diseases, and tuberculous pleural effusion (TPE) is the most common cause of pleural effusion in TB-endemic areas and the most common type of exudative pleural effusion in China. In clinical practice, distinguishing TPE from pleural effusion caused by other reasons remains a relatively challenging issue. The objective of present study was to explore the clinical significance of the pleural fluid lactate dehydrogenase/adenosine deaminase ratio (pfLDH/pfADA) in the diagnosis of TPE., Methods: The clinical data of 618 patients with pleural effusion were retrospectively collected, and the patients were divided into 3 groups: the TPE group (412 patients), the parapneumonic pleural effusion (PPE) group (106 patients), and the malignant pleural effusion (MPE) group (100 patients). The differences in the ratios of pleural effusion-related and serology-related indicators were compared among the three groups, and receiver operating characteristic curves were drawn to analyze the sensitivity and specificity of the parameter ratios of different indicators for the diagnosis of TPE., Results: The median serum ADA level was higher in the TPE group (13 U/L) than in the PPE group (10 U/L, P < 0.01) and MPE group (10 U/L, P < 0.001). The median pfADA level in the TPE group was 41 (32, 52) U/L; it was lowest in the MPE group at 9 (7, 12) U/L and highest in the PPE group at 43 (23, 145) U/L. The pfLDH level in the PPE group was 2542 (1109, 6219) U/L, which was significantly higher than that in the TPE group 449 (293, 664) U/L. In the differential diagnosis between TPE and non-TPE, the AUC of pfLDH/pfADA for diagnosing TPE was the highest at 0.946 (0.925, 0.966), with an optimal cutoff value of 23.20, sensitivity of 93.9%, specificity of 87.0%, and Youden index of 0.809. In the differential diagnosis of TPE and PPE, the AUC of pfLDH/pfADA was the highest at 0.964 (0.939, 0.989), with an optimal cutoff value of 24.32, sensitivity of 94.6%, and specificity of 94.4%; this indicated significantly better diagnostic efficacy than that of the single index of pfLDH. In the differential diagnosis between TPE and MPE, the AUC of pfLDH/pfADA was 0.926 (0.896, 0.956), with a sensitivity of 93.4% and specificity of 80.0%; this was not significantly different from the diagnostic efficacy of pfADA., Conclusions: Compared with single biomarkers, pfLDH/pfADA has higher diagnostic value for TPE and can identify patients with TPE early, easily, and economically., (© 2024. The Author(s).)

Purpose of Review: Tuberculous pleuritis (TBP) is one of the most common types of extrapulmonary tuberculosis. We highlight the latest epidemiology of TBP, the heterogeneity of its presentation and the performance of different diagnostic strategies., Recent Findings: There are differential trends in the incidences of TBP worldwide. Its incidence increased in China but decreased in the United States in the past decade. The presentation of TBP is heterogeneous regarding clinical symptoms, radiological findings and pleural fluid analysis results. Conventional microbiological tests have low sensitivities to diagnose TBP. Recent research focused on various diagnostic tools with better yield. The sensitivity of nucleic acid amplification tests (NAAT) in pleural fluid, including the latest generation of PCR and sequencing-based techniques for detecting tuberculosis, remains suboptimal. Various pleural fluid biomarkers have been explored, but there is a lack of consensus on their clinical utility and cutoff levels., Summary: The heterogeneity of clinical presentation poses obstacles to diagnosing TBP. Further development of diagnostic tools, including more robust NAAT and biomarkers with additional validation, is needed before incorporation into routine clinical practice., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Tuberculous pleural effusion (TPE) stands as one of the primary forms of extrapulmonary tuberculosis (TB) and frequently manifests in regions with a high prevalence of TB, consequently being a notable cause of pleural effusion in such areas. However, the differentiation between TPE and parapneumonic pleural effusion (PPE) presents diagnostic complexities. This study aimed to evaluate the potential of myeloid-derived suppressor cells (MDSCs) in the pleural fluid as a potential diagnostic marker for distinguishing between TPE and PPE., Methods: Adult patients, aged 18 years or older, who presented to the emergency room of a tertiary referral hospital and received a first-time diagnosis of pleural effusion, were prospectively enrolled in the study. Various immune cell populations, including T cells, B cells, natural killer (NK) cells, and MDSCs, were analyzed in both pleural fluid and peripheral blood samples., Results: In pleural fluid, the frequency of lymphocytes, including T, B, and NK cells, was notably higher in TPE compared to PPE. Conversely, the frequency of polymorphonuclear (PMN)-MDSCs was significantly higher in PPE. Notably, compared to traditional markers such as the neutrophil-to-lymphocyte ratio and adenosine deaminase level, the frequency of PMN-MDSCs emerged as a more effective discriminator between PPE and TPE. PMN-MDSCs demonstrated superior positive and negative predictive values and exhibited a higher area under the curve in the receiver operating characteristic curve analysis. PMN-MDSCs in pleural effusion increased the levels of reactive oxygen species and suppressed the production of interferon-gamma from T cells following nonspecific stimulation. These findings suggest that MDSC-mediated immune suppression may contribute to the pathology of both TPE and PPE., Discussion: The frequency of PMN-MDSCs in pleural fluid is a clinically useful indicator for distinguishing between TPE and PPE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kim, Islam, Lee, Seong, Youn, Kwon, Kim and Lee.)

Background: Exudative pleural effusions are commonly encountered in clinical practice, but in about one-fourth of cases, etiology remains elusive after initial evaluation. Medical thoracoscopy with semirigid thoracoscope is a minimally invasive procedure with high diagnostic yield for diagnosing pleural diseases, especially these undiagnosed exudative pleural effusions. In tubercular endemic areas, often, these effusions turn out to be tubercular, but the diagnosis of tubercular pleural effusion is quite challenging due to the paucibacillary nature of the disease. Although culture is the gold standard, it is time-consuming. Cartridge-based nucleic acid amplification test (CBNAAT) is a novel rapid diagnostic test for tuberculosis (TB) and has been recommended as the initial diagnostic test in patients suspected of having extrapulmonary TB (EPTB)., Materials and Methods: We conducted a prospective observational study of 50 patients with undiagnosed pleural effusion admitted to our tertiary care hospital. The primary aim of the study is to evaluate the diagnostic performance of CBNAAT on thoracoscopic guided pleural biopsy and compare it with conventional diagnostic techniques like histopathology and conventional culture., Results: Of 50 undiagnosed pleural effusions, TB (50%) was the most common etiology. The overall diagnostic yield of semirigid thoracoscopy in this study was 74%. Our study showed that CBNAAT of pleural biopsies had a sensitivity of 36% only but a specificity of 100%. The sensitivity of CBNAAT was not far superior to the conventional culture., Conclusion: Tuberculosis (TB) is a common cause of undiagnosed pleural effusion in our set-up. CBNAAT testing of pleural biopsy, though, is a poor rule-out test for pleural TB, but it may aid in the early diagnosis of such patients., (© Journal of the Association of Physicians of India 2024.)

Background: Lipoarabinomannan (LAM) antigen serves as an attractive biomarker to diagnose Tuberculosis (TB). Given the limitations of current diagnostic modalities for Pleural TB, current study evaluated LAM's potential to serve as a point-of-care test to diagnose pleural TB., Methods: A cross sectional, diagnostic accuracy study was conducted during February to November 2021 in a tertiary care hospital in India. LAM antigen detection was performed on pleural fluid as well as early morning urine specimen of suspected pleural TB patients by "Alere/ Abott Determine TB LAM" lateral flow assay (LAM-LFA). The results were compared to microbiological reference standards/MRS (Mycobacterial culture or NAAT) and Composite reference standards/CRS (MRS plus Clinico-radiological diagnosis)., Results: A total of 170 subjects were included in the analysis, including 26 with Definite TB, 22 with Probable TB, and 122 with No TB. Compared to MRS and CRS, the sensitivity (61.54% & 45.83%) and positive predictive value (PPV) (57.14 & 78.57%) of Pleural LAM-LFA testing were found to be suboptimal, whereas the specificity (91.67% & 95.08%) and negative predictive value (NPV) (92.96% & 81.69%) of the assay were found to be good. Urinary LAM-LFA performed even worse than pleural LAM-LFA, except for its higher specificity against MRS and CRS (97.2% and 98.3%, respectively). Specificity and PPV of pleural LAM detection increased to 100% when analysed in a subgroup of patients with elevated ADA levels (receiver operating curve analysis-derived cut off value > 40 IU/ml)., Conclusion: Detection of LAM antigen by LFA directly from pleural fluid was found to be a useful test to predict absence of the disease if the test is negative rather than using as a POCT for diagnosis., (© 2024. The Author(s).)

Objective: Early diagnosis and differential diagnosis of tuberculous pleural effusion (TPE) remains challenging and is critical to the patients' prognosis. The present study aimed to develop nine machine learning (ML) algorithms for early diagnosis of TPE and compare their performance., Methods: A total of 1435 untreated patients with pleural effusions (PEs) were retrospectively included and divided into the training set (80%) and the test set (20%). The demographic and laboratory variables were collected, preprocessed, and analyzed to select features, which were fed into nine ML algorithms to develop an optimal diagnostic model for TPE. The proposed model was validated by an independently external data. The decision curve analysis (DCA) and the SHapley Additive exPlanations (SHAP) were also applied., Results: Support vector machine (SVM) was the best model in discriminating TPE from non-TPE, with a balanced accuracy of 87.7%, precision of 85.3%, area under the curve (AUC) of 0.914, sensitivity of 94.7%, specificity of 80.7%, and F1-score of 86.0% among the nine ML algorithms. The excellent diagnostic performance was also validated by the external data (a balanced accuracy of 87.7%, precision of 85.2%, and AUC of 0.898). Neural network (NN) and K-nearest neighbor (KNN) had better net benefits in clinical usefulness. Besides, PE adenosine deaminase (ADA), PE carcinoembryonic antigen (CEA), and serum CYFRA21-1 were identified as the top three important features for diagnosing TPE., Conclusions: This study developed and validated a SVM model for the early diagnosis of TPE, which might help clinicians provide better diagnosis and treatment for TPE patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Pleural tuberculosis (PlTB), the most common site of extrapulmonary TB, is characterized by a paucibacillary nature and a compartmentalized inflammatory response in the pleural cavity, both of which make diagnosis and management extremely challenging. Although transcriptional signatures for pulmonary TB have already been described, data obtained by using this approach for extrapulmonary tuberculosis and, specifically, for pleural tuberculosis are scarce and heterogeneous. In the present study, a set of candidate genes previously described in pulmonary TB was evaluated to identify and validate a transcriptional signature in clinical samples from a Brazilian cohort of PlTB patients and those with other exudative causes of pleural effusion., Methods: As a first step, target genes were selected by a random forest algorithm with recursive feature elimination (RFE) from public microarray datasets. Then, peripheral blood (PB) and pleural fluid (PF) samples from recruited patients presenting exudative pleural effusion were collected during the thoracentesis procedure. Transcriptional analysis of the selected top 10 genes was performed by quantitative RT-PCR (RT-qPCR)., Results: Reanalysis of the public datasets identified a set of candidate genes ( CARD17, BHLHE40, FCGR1A, BATF2, STAT1, BTN3A1, ANKRD22, C1QB, GBP2 , and SEPTIN4 ) that demonstrated a global accuracy of 89.5% in discriminating pulmonary TB cases from other respiratory diseases. Our validation cohort consisted of PlTB ( n = 35) patients and non-TB ( n = 34) ones. The gene expressions of CARD17 , GBP2 , and C1QB in PF at diagnosis were significantly different between the two (PlTB and non-TB) groups ( p < 0.0001). It was observed that the gene expressions of CARD17 and GBP2 were higher in PlTB PF than in non-TB patients. C1QB showed the opposite behavior, being higher in the non-TB PF. After anti-TB therapy, however, GBP2 gene expression was significantly reduced in PlTB patients ( p < 0.001). Finally, the accuracy of the three above-cited highlighted genes in the PF was analyzed, showing AUCs of 91%, 90%, and 85%, respectively. GBP2 was above 80% (sensitivity = 0.89/specificity = 0.81), and CARD17 showed significant specificity (Se = 0.69/Sp = 0.95) in its capacity to discriminate the groups., Conclusion: CARD17 , GBP2 , and C1QB showed promise in discriminating PlTB from other causes of exudative pleural effusion by providing accurate diagnoses, thus accelerating the initiation of anti-TB therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Corrêa, Leal-Calvo, Mafort, Santos, Leung, Pinheiro, Rufino, Moraes and Rodrigues.)

Background: Adenosine deaminase (ADA) is a useful biomarker for the diagnosis of tuberculous pleurisy (TBP). However, pleural effusions with high ADA can also be caused by other diseases, particularly hematologic malignant pleural effusion (hMPE). This study aimed to investigate the features that could differentiate TBP and hMPE in patients with pleural effusion ADA ≥ 40 IU/L., Methods: This was a retrospective observational study of patients with pleural effusion ADA ≥ 40 IU/L, conducted at a Korean tertiary referral hospital with an intermediate tuberculosis burden between January 2010 and December 2017. Multivariable logistic regression analyses were performed to investigate the features associated with TBP and hMPE, respectively., Results: Among 1134 patients with ADA ≥ 40 IU/L, 375 (33.1%) and 85 (7.5%) were diagnosed with TBP and hMPE, respectively. TBP and hMPE accounted for 59% (257/433) and 6% (27/433) in patients with ADA between 70 and 150 IU/L, respectively. However, in patients with ADA ≥ 150 IU/L, they accounted for 7% (9/123) and 19% (23/123), respectively. When ADA between 40 and 70 IU/L was the reference category, ADA between 70 and 150 IU/L was independently associated with TBP (adjusted odds ratio [aOR], 3.11; 95% confidence interval [CI], 1.95-4.95; P < 0.001). ADA ≥ 150 IU/L was negatively associated with TBP (aOR, 0.35; 95% CI, 0.14-0.90; P = 0.029) and positively associated with hMPE (aOR, 13.21; 95% CI, 5.67-30.79; P < 0.001). In addition, TBP was independently associated with lymphocytes ≥ 35% and a lactate dehydrogenase (LD)/ADA ratio < 18 in pleural effusion. hMPE was independently associated with pleural polymorphonuclear neutrophils < 50%, thrombocytopenia, and higher serum LD. A combination of lymphocytes ≥ 35%, LD/ADA < 18, and ADA < 150 IU/L demonstrated a sensitivity of 0.824 and specificity of 0.937 for predicting TBP., Conclusion: In patients with very high levels of pleural effusion ADA, hMPE should be considered. Several features in pleural effusion and serum may help to more effectively differentiate TBP from hMPE., (© 2023. The Author(s).)

Background: Patients with tuberculous empyema (TE) can have a serious impact on lung function as their disease progresses, and, if left untreated, can cause damage to other parts of the body such as the thorax and spine, causing pain and inconvenience to the patient. Early diagnosis and the search for appropriate treatment are key to improving the survival rate of the disease., Methods: We report a case of a young patient with an unexpected finding of right pleural effusion on physical examination, who was eventually diagnosed with TE using next-generation sequencing of pleural tissue. We analyzed the literature to improve clinicians' understanding of TE and how to properly diagnose and treat the disease., Results: Laboratory results of the pleural effusion suggested a possible Mycobacterium tuberculosis infection, but pathogen-related tests were negative, and the diagnosis was eventually successfully confirmed by thoracoscopic pleural biopsy., Conclusions: The diagnosis of TE should be considered in young patients with pleural thickening of the empyema. Adenosine deaminase may provide diagnostic direction in patients with unexplained thorax abscess. Pleural biopsy, although an invasive procedure, is an essential diagnostic tool in some cases.

Tuberculosis (TB) is the leading cause of pleural exudative effusions. Inflammatory markers, such as IFNγ and ADA, have been used as proxies for its diagnosis. We evaluated ex vivo levels of several cytokines in 83 pleural effusion specimens from patients with TB (including 10 with HIV co-infection) and 26 patients with other pleuritis using multiplex and ELISA assays. IL-6 and IL-27 levels were higher (p ≤ 0.04) in TB patients, regardless of the HIV status and the approach. IL-2, IL-4, IL-8, IFNγ, TNF and G-CSF showed variable results depending on the assay. This warranty these markers to be further validated., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Several markers for the diagnosis of pleural effusion have been reported; however, a comprehensive evaluation using those markers has not been performed. Therefore, this study aimed to develop a diagnostic flowchart for tuberculous pleurisy, pleural infection, malignant pleural effusion, and other diseases by using these markers., Methods: We retrospectively collected data from 174 patients with tuberculous pleurisy, 215 patients with pleural infection other than tuberculous pleurisy, 360 patients with malignant pleural effusion, and 209 patients with other diseases at Fukujuji Hospital from January 2012 to October 2022. The diagnostic flowchart for four diseases was developed by using several previously reported markers., Results: The flowchart was developed by including seven markers: pleural ADA ≥40 IU/L, pleural fluid LDH <825 IU/L, pleural fluid ADA/TP < 14, neutrophil predominance or cell degeneration, peripheral blood WBC ≥9200/μL or serum CRP ≥12 mg/dL, pleural amylase ≥75 U/L, and the presence of pneumothorax according to the algorithm of a decision tree. The accuracy ratio of the flowchart was 71.7 % for the diagnosis of the four diseases, with 79.3 % sensitivity and 75.4 % positive predictive value (PPV) for tuberculosis pleurisy, 75.8 % sensitivity and 83.2 % PPV for pleural infection, 88.6 % sensitivity and 68.8 % PPV for malignant pleural effusion, and 33.0 % sensitivity and 60.0 % PPV for other diseases in the flowchart. The misdiagnosis ratios were 4.6 % for tuberculosis pleurisy, 6.8 % for pleural infection, and 8.3 % for malignant pleural effusion., Conclusion: This study developed a useful diagnostic flowchart for tuberculous pleurisy, pleural infection, malignant pleural effusion, and other diseases., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2023 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)