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Introduction: There is a clinical challenge in diagnosing tuberculous pleurisy accurately and promptly, highlighting the urgent need for a rapid and sensitive diagnostic method. This study aimed to evaluate the diagnostic accuracy of metagenomic next-generation sequencing (mNGS) and GeneXpert Mycobacterium tuberculosis (MTB) for identifying tuberculous pleurisy and analyzing the microbial profiles of both tuberculous and non-tuberculous pleural effusions., Methods: The study enrolled 31 patients with suspected tuberculous pleurisy, of which 15 were confirmed to have tuberculous pleurisy and subsequently allocated to the tuberculous pleurisy group (TP group), while the remaining 16 individuals were assigned to the non-tuberculous pleurisy group (NTP group). mNGS and GeneXpert MTB were performed on pleural effusion samples, and the diagnostic accuracy of both tests was compared. We employed established formulas to compute crucial indicators, including sensitivity, specificity, missed diagnosis rate, misdiagnosed rate, positive predictive value (PPV), and negative predictive value (NPV)., Results: The results showed that both tests had high specificity (100%) and positive predictive value (100%) for detecting tuberculous pleurisy, along with comparable sensitivity (46.67% for mNGS and 40.0% for GeneXpert MTB). Further analysis of the combined efficacy of mNGS and GeneXpert MTB showed that the combined test had a sensitivity of 66.67% and a specificity of 100%. mNGS analysis revealed that MTB was detected in 7 out of 15 patients with tuberculous pleural effusions, while non-tuberculous pleural effusions were associated with a diverse range of microbial genera and species. The most frequently detected genera at the microbial genus level in the NTP group were Microbacterium spp. (6/16), Prevotella spp. (5/16), and Campylobacter spp. (5/16)., Discussion: These findings suggest that mNGS and GeneXpert MTB are useful diagnostic tools for identifying patients with tuberculous pleurisy, and mNGS can provide valuable insights into the microbial profiles of both tuberculous and non-tuberculous pleural effusions., 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 © 2023 Huang, Wang, Qiao, Peng, Zhao and Miao.)

Background: Pleural effusion (PE) is a common clinical feature that presents a diagnostic challenge for clinicians. In this retrospective study, we aimed to assess the biomarkers, ratios, and multiple indicators in serum and Pleural effusion for the differential diagnosis of tuberculous pleural effusion (TPE) from non-tuberculosis effusion (non-TPE)., Methods: The participants, who were divided into two groups: TPE and non-TPE (MPE and PPE), from Ningbo First Hospital, were incorporated in this study. The clinical and laboratory features were collected and analyzed using logistic regression analysis. Twelve biomarkers and their ratios in serum and PE were investigated for TPE versus non-TPE. Additionally, the value of multiple indicators for joint diagnosis was estimated., Results: Biomarkers and ratios showed good diagnostic performance. The five variables including Serum ADA, IGRA, Effusion ADA, Effusion ADA/Serum ADA and Effusion LDH/Effusion ADA were identified as valuable parameters for differential diagnosis of TPE from non-TPE. The combined diagnosis of the five indexes yielded the highest diagnostic accuracy for TPE with an AUC (0.919), sensitivity (90.30%), and specificity (94.50%)., Conclusions: The biomarkers and ratios demonstrated strong diagnostic performance, and the utilization of multiple indicators for joint diagnosis can improve the diagnostic efficacy of tuberculous pleurisy., (© 2023. The Author(s).)

Background: Tuberculous effusion varies from lymphocyte-dominant to neutrophilic effusion according to inflammation status. The criteria of adenosine deaminase (ADA) and lymphocyte/neutrophil (L/N) ratio have yet not been evaluated across different disease conditions., Methods: Patients who conducted pleural fluid analysis from 2009 to 2019 at Asan Medical Center were included. Criteria (ADA of 50 and L/N ratio of 0.75) were evaluated by quantile subgroups according to age, C-reactive protein (CRP), white blood cell (WBC), and lactate dehydrogenase (LD) by the Monte Carlo simulation method to diagnose tuberculosis. The model for the ADA and L/N ratio was evaluated by AUROC., Results: Among the 2,918 reviewed cases, 2034 were included with 229 (11.26%) tuberculosis cases. The mean baseline ADA AUROC was 0.88 across all patients. Increased CRP and WBC showed high proportions of neutrophilic tuberculous effusion, with low sensitivity of approximately 45% and 33% in the fifth WBC and CRP groups, respectively. The AUROC of the models decreased with the increase in WBC and CRP groups (ADA model: 0.69 [the top quantile WBC group], 0.74 [the top quantile CRP group]). The AUROC of the models did not show a trend according to the increase in LD and age., Conclusion: Inflammatory status affects the diagnostic metrics for tuberculous effusion due to the progression of tuberculous effusion. Clinicians should consider the low accuracy of tuberculous effusion criteria in high-inflammatory conditions when diagnosing tuberculosis., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Thoracoscopic pleural biopsy is the gold standard for diagnosing tubercular pleural effusion (TPE). Various thoracoscopic appearances like sago grain nodules, caseous necrosis, and adhesions have been described in TPE. However, none of these have high specificity for diagnosing TPE. In this study we evaluate a novel finding on thoracoscopy, the " Pleural Pustule.", Methods: This is a retrospective analysis of patients who underwent thoracoscopy for undiagnosed pleural effusion. Visual inspection of the pleura was performed to identify abnormalities. Biopsies were obtained from those areas and sent for histopathology, acid fast bacillus (AFB) smear, culture, and Xpert MTB/Rif assay. Pleural pustule was defined as a pus filled nodule on the pleural surface., Results: Of the 259 patients included, 92 were diagnosed with TPE. Pleural pustule(s) were identified in 16 patients with TPE. Presence of pleural pustule had a sensitivity, specificity, positive predictive value, and negative predictive value of 17.4%, 100%, 100% and 68.7%, respectively, for diagnosing TPE. Histopathology of pleural pustule demonstrated necrotizing granulomas in all. In patients with pleural pustule, a microbiological diagnosis of tuberculosis was achieved in 93.7% patients (AFB smear, Xpert MTB/Rif assay, and MTB culture positive in 31.3%, 93.7%, and 43.7% cases, respectively). There is a strong association between pleural pustule and positive Xpert MTB/Rif assay ( P =0.002) and microbiologic confirmation of diagnosis ( P =0.017)., Conclusion: The presence of pleural pustule on thoracoscopy has a high positive predictive value for TPE. In tuberculosis-endemic countries, this can be considered suggestive for TPE. When identified, a biopsy from the pleural pustule should be performed as it will likely yield a positive microbiologic diagnosis., Competing Interests: Disclosure: There is no conflict of interest or other disclosures., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Metagenomic next-generation sequencing (mNGS) has become a powerful tool for pathogen detection, but the value of human sequencing reads generated from it is underestimated., Methods: A total of 138 patients with pleural effusion (PE) were diagnosed with tuberculous pleurisy (TBP, N = 82), malignant pleural effusion (MPE, N = 35), or non-TB infection (N = 21), whose PE samples all underwent mNGS analysis. Clinical TB tests including culture, Acid-Fast Bacillus (AFB) test, Xpert, and T-SPOT, were performed. To utilize mNGS for MPE identification, 25 non-MPE samples (20 TBP and 5 non-TB infection) were randomly selected to set human chromosome copy number baseline and generalized linear modeling was performed using copy number variant (CNV) features of the rest 113 samples (35 MPE and 78 non-MPE)., Results: The performance of TB detection was compared among five methods. T-SPOT demonstrated the highest sensitivity (61% vs. culture 32%, AFB 12%, Xpert 35%, and mNGS 49%) but with the highest false-positive rate (10%) as well. In contrast, mNGS was able to detect TB-genome in nearly half (40/82) of the PE samples from TBP subgroup, with 100% specificity. To evaluate the performance of using CNV features of the human genome for MPE prediction, we performed the leave-one-out cross-validation (LOOCV) in the subcohort excluding the 25 non-MPE samples for setting copy number standards, which demonstrated 54.1% sensitivity, 80.8% specificity, 71.7% accuracy, and an AUC of 0.851., Conclusion: In summary, we exploited the value of human and non-human sequencing reads generated from mNGS, which showed promising ability in simultaneously detecting TBP and MPE., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Rapid and accurate methods for the diagnosis of tuberculous pleurisy (TP) are urgently needed. Activation markers of tuberculosis (TB)-reactive T cells are considered promising for the diagnosis of active TB (ATB). Different activation indexes may play different roles in the progression of TB, but there are few reports on T cell activation indicators, except for HLA-DR. Hence, we evaluated the expression of early (CD25 and CD69) and late (CD134) activation markers on TB antigen-stimulated CD4+ T cells in populations with different TB infection status and investigated their diagnostic value for ATB, particularly, for TP. Moreover, we compared the differences in the diagnostic efficacy among the indexes from peripheral blood (PB) and pleural fluid (PF) for TP. The expression of each activation marker was significantly increased in TB-infected populations (patients with ATB and latent TB infection vs. healthy individuals; patients with TP vs. non-TP) and was significantly higher in the PF than in the PB of patients with TP. The diagnostic performance of the coexpressed activation markers was superior to that of single expression markers in the differential diagnosis of ATB and non-TB, with CD25+CD134+ showing the best diagnostic efficiency (AUC: 0.93, 95% CI, 0.87-0.99; sensitivity: 86.7%, 95% CI, 72.5%-94.5%; and specificity: 94.0%, 95% CI, 82.5%-98.4%). Except for TB-IGRA, the activation indexes were more accurate than conventional laboratory methods for ATB diagnosis. In addition, the expression of CD25+CD134+ in PB and PF was the best values for differential diagnosis of TP and NTP, with AUCs of 0.87 (95% CI, 0.77-0.96) and 0.95 (95% CI, 0.90-1.00), respectively. Our study provides information on the diagnostic value of different activation markers for TB and shows that the expression of CD25+CD134+ on CD4+ T cells in PF can serve as a potential marker for TP diagnosis., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Hanlu Shi et al.)

Pleural tuberculosis (pTB) is a grave clinical challenge. A novel cell-free M. tuberculosis DNA (cfM.tb-DNA) probe-based-qPCR assay was developed for the diagnosis of pTB. Total cell-free DNA was extracted from pleural fluid (PF) and paired plasma samples and cfM.tb-DNA was quantified by probe-based qPCR targeting devR (109-bp) gene of M. tuberculosis in patients with pleural effusion. Patient categorization was done using 'Composite-Reference-Standard' formulated for the study. Assay cut-offs were determined from samples in the 'Development set' (n = 17; 'Definite & Probable' pTB; n = 9 and 'Non-TB'; n = 8) by ROC-curve analysis and applied to 'Validation set' (n = 112; 'Definite' pTB; n = 8, 'Probable' pTB; n = 34, 'Possible' pTB; n = 28 and 'Non-TB'; n = 42). cfM.tb-DNA qPCR had a sensitivity of 62.5% (95%CI; 24.4,91.4) in 'Definite' pTB category and 59.5% (95%CI; 43.2,74.3) in 'Definite & Probable' pTB category with 95.2% (95%CI; 83.8,99.4) specificity using PF. In plasma (n = 85), the assay had a sub-optimal sensitivity of 7.6% (95%CI; 0.95,25.1) with 88.2% (95%CI; 72.5,96.7) specificity in 'Definite & Probable' pTB group. Xpert MTB/RIF assay detected only six-samples in the 'Validation set'. Logistic regression analysis indicated that PF-cfM.tb-DNA qPCR provided incremental advantage over existing pTB diagnostic algorithms. To the best of our knowledge, this is the first report describing the utility of cfM.tb-DNA for pTB diagnosis in India., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Patients with pulmonary tuberculosis may present with deterioration of pleural effusion during anti-tuberculosis therapy, referred to as a paradoxical response (PR), with some patients requiring additional intervention. However, PR may be confused with other differential diagnoses, and the predictive factors for recommending additional therapies are unknown. Therefore, this study aimed to reveal useful information for the diagnosis and intervention of PR., Methods: Data from human immunodeficiency virus-negative patients with tuberculous pleurisy (n = 210), including 184 patients with pre-existing pleural effusion and 26 patients with PR at Fukujuji Hospital, were retrospectively collected from January 2012 to December 2022 and compared. Furthermore, patients with PR were divided into the intervention group (n = 9) and the no intervention group (n = 17) and were compared., Results: Patients in the PR group had lower pleural lactate dehydrogenase (LDH) (median 177 IU/L vs. 383 IU/L, p < 0.001) and higher pleural glucose (median 122 mg/dL vs. 93 mg/dL, p < 0.001) levels than those in the preexisting pleural effusion group. Other pleural fluid data were not significantly different. Patients in the intervention group had a shorter duration from the initiation of anti-tuberculosis therapy to the development of PR than patients in the no intervention group (median 19.0 days [interquartile range (IQR): 18.0-22.0] vs. median 37.0 days [IQR: 28.0-58.0], p = 0.012)., Conclusion: This study demonstrates that, apart from lower pleural LDH and elevated pleural glucose levels, PR presents with similar features to preexisting pleural effusion and that patients who develop PR faster tend to require intervention., Competing Interests: Declaration of competing interest The authors state that they have no conflicts of interest., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Differentiating tuberculous pleural effusion (TPE) from non-tuberculosis pleural effusion remains a challenge in clinical practice. This study aimed to develop and externally validate a novel prediction model using the peripheral blood tuberculous infection of T cells spot test (T-SPOT.TB) to assess the probability of TPE in patients with unexplained pleural effusion. Patients with pleural effusion and confirmed etiology were included in this study. A retrospective derivation population was used to develop and internally validate the predictive model. Clinical, radiological, and laboratory features were collected, and important predictors were selected using the least absolute shrinkage and selection operator. The prediction model, presented as a web calculator, was developed using multivariable logistic regression. The predictive performance of the model was evaluated for discrimination and calibration and verified in an independent validation population. The developed prediction model included age, positive T-SPOT.TB result, logarithm of the ratio of mononuclear cells to multiple nuclear cells in pleural effusion (lnRMMPE), and adenosine deaminase in pleural effusion ≥ 40 U/L. The model demonstrated good discrimination [with area under the curve of 0.837 and 0.903, respectively] and calibration (with a Brier score of 0.159 and 0.119, respectively) in both the derivation population and the validation population. Using a cutoff value of 60%, the sensitivity and specificity for identifying TPE were 70% and 88%, respectively, in the derivation population, and 77% and 92%, respectively, in the validation population. A novel predictive model based on T-SPOT.TB was developed and externally validated, demonstrating good diagnostic performance in identifying TPE., (© 2023. The Author(s).)

Context: Tuberculous pleurisy (TP) is the most common manifestation of extrapulmonary tuberculosis and the most frequent cause of pleural effusion (PE). Clinicians make a definitive diagnosis of TP based on the isolation of the mycobacterium tuberculosis (MTB) from PE or a pleural biopsy. Since the currently available tests for TP all have limitations in making a definitive diagnosis, clinicians urgently need new diagnostic tests., Objective: The study intended to compare the value in clinically diagnosing TP of the paraffin-embedded sample test (PEST), using pleural-effusion samples; an adenosine deaminase assay (ADA) using pleural fluid; and the T cell enzyme-linked immunospot test (T-SPOT), using peripheral-blood., Design: The research team performed a retrospective observational study., Setting: The study took place at the Sir Run Run Hospital, Nanjing Medical University in Nanjing, Jiangsu, China., Participants: Participants were 37 patients with suspected TP who had been admitted to the hospital between September 2018 and December 2022., Outcome Measures: The research team assessed the diagnostic performance of PEST, ADA, and T-SPOT in the TP group, calculating the positive rate, sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of the tests., Results: Among the 37 participants, the testing confirmed that 24 had TP (64.86%), with 13 not having TP (35.14%). The PEST test produced a sensitivity of 83.3% for TP, with 20 out of 24 participants in the TP group testing positive (95% CI: 61.8 to 94.5), which was superior to the ADA, with only 9 out of the 24 participants (37.5%) in the TP group testing positive (95% CI: 19.6 to 59.2), with P < .001., Conclusions: The PEST test possesses a high diagnostic value, and clinicians can use it as a time-saving, noninvasive, and highly sensitive method for TP diagnosis. It can be adjunct method to the currently used tests for diagnosing TP. A combination of several detection methods could promote effective treatment.

Background: Diagnosis of pleural tuberculosis (TB) is tedious owing to its close resemblance with malignant pleural effusion and sparse bacterial load in clinical specimens. There is an immediate need to design a rapid and dependable diagnostic test to prevent unnecessary morbidity/mortality., Research Design and Methods: A multi-targeted loop-mediated isothermal amplification (MT-LAMP) was deliberated using mpt64 and IS6110 to diagnose pleural TB within pleural fluids/biopsies. MT-LAMP products were analyzed by gel-based and visual detection methods, viz. SYBR Green I, SYBR Green I+deoxyuridine triphosphate uracil-N-glycosylase (dUTP-UNG), and dry methyl green reactions., Results: In a pilot study, while assessing pleural TB/non-TB control subjects ( n  = 40), both SYBR Green I+dUTP-UNG/gel-based MT-LAMP assays exhibited better sensitivity/specificity than SYBR Green I and dry methyl green MT-LAMP. Since it is facile to work with SYBR Green I+dUTP-UNG than gel-based MT-LAMP, we validated the performance of SYBR Green I+dUTP-UNG in a higher number of specimens ( n  = 97), which revealed somewhat higher sensitivity (85.2 vs. 81.5%) and specificity (97.7 vs. 90.7%) than SYBR Green I MT-LAMP. Furthermore, the sensitivity attained by SYBR Green I+dUTP-UNG MT-LAMP was significantly higher ( p  < 0.001) than GeneXpert., Conclusions: Our SYBR Green I+dUTP-UNG MT-LAMP is a simple and reliable method to diagnose pleural TB, which may translate into a point-of-care test.

Pleurisy and pleural effusion caused by Brucella infection are rare. However, clinicians lack an understanding of these possibilities, and the underlying disorder is easy to misdiagnose. We report a 52-year-old male farmer who was admitted to hospital with a fever, chest pain, and shortness of breath. Closed chest drainage was performed by thoracocentesis, and the concentration of adenosine deaminase (ADA) in the pleural fluid was >45 U/L. Mononuclear cells in the pleural fluid accounted for 90% of the cells, and pathology indicated a large number of lymphocytes. The clinical diagnosis was tuberculosis with tuberculous pleurisy. However, subsequent pleural fluid culture results did not support tuberculous pleurisy. The results of pleural fluid culture indicated Brucella , and the results of Brucella tiger red plate agglutination indicated a titer of 1:400 (+++). The final diagnosis was brucellosis with pneumonia and pleurisy. After 12 weeks of oral treatment, the patient underwent follow-up chest radiographs. Radiography indicated complete resolution of the hydrothorax and pneumonia, and the patient reported no discomfort. The short-term curative effect was excellent. Pleurisy associated with brucellosis should be considered a differential for pleurisy in regions where brucellosis is endemic, to minimize the risk of misdiagnosis.

Background: The aim of this study was to explore the difference in activated partial thromboplastin time (APTT) levels in patients with tuberculous and non-tuberculous pleural effusion (TPE and non-TPE) and its possible mechanism to provide a new direction for the diagnosis of pleural effusion (PE)., Methods: A total of 61 patients diagnosed with tuberculous pleurisy with pleural effusion at Shunde Hospital of Southern Medical University from July 2013 to September 2020 were selected as the observation group (tuberculosis group). Another 89 patients (45 with malignant pleural effusion (MPE) and 44 with parapneumonic pleural effusion (PPE) composed the control group. The adenosine deaminase (ADA) level in pleural fluid and plasma APTT level were measured in the two groups., Results: The levels of APTT and ADA in the TPE group were significantly higher than the control group, and were 40.03 (37.00, 42.60) (s) and 55.00 (47.00, 69.25) (U/L) for TPE, 29.50 (25.45, 34.20) (s) and 11.90 (9.15, 19.05) (U/L) for malignant pleural effusion (MPE) and 31.35 (27.43, 35.76) (s) and 15.15 (7.40, 35.00) (U/L) for parapneumonic pleural effusion (PPE), respectively., Conclusions: The level of plasma APTT has certain significance in differentiating tuberculous pleural effusion from nontuberculous pleural effusion., Competing Interests: Declaration of Competing Interest The authors claim that no conflicts of interest were involved in this study., (Copyright © 2023. Published by Elsevier Inc.)

Background and Aims: Complement activation is essential for tuberculosis pleural effusion. However, little is known about the value of complement regulatory protein (CD46, CD55, and CD59) in the differential diagnosis of tuberculosis., Materials and Methods: Ninety-nine patients with exudative pleural effusion admitted to Xiangya Hospital of Central South University from June 1, 2021to November 14, 2022 were enrolled. The expression levels of soluble CD46 (sCD46), soluble CD55 (sCD55), and soluble CD59 (sCD59) in pleural effusion were quantified by enzyme-linked immunosorbent assay, and the receiver operating characteristic (ROC) curves were plotted to evaluate the diagnostic and co-diagnostic values., Results: The ADA level is higher in TPE patients than non-TPE patients. It is well-found that TPE patients had lower levels of sCD46, sCD55, and sCD59 compared with non-TPE patients. Moreover, the expression of sCD46, sCD55, and sCD59 in pleural effusion was negatively correlated with ADA. In addition, the diagnostic efficacy of sCD46, sCD55 and sCD59 was comparable to that of ADA, with 0.896, 0.857, 0.858 and 0.893, respectively. Furthermore, combine detection of sCD46, sCD55, sCD59 and ADA could improve the diagnostic accuracy., Conclusions: Complement regulatory factors (CD46, CD55, and CD59) were validated by this project to be promising candidate biomarkers for the diagnosis of TPE with high accuracy. The combination of the CD46, CD55, and CD59 and ADA assay exist a better diagnostic value in TPE., 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 © 2023 Tang, Hu, Li, Deng, Jiang, Luo, Cai, Yang, Wu, Gong and Feng.)

There is a lack of objective tools for monitoring treatment response in extrapulmonary tuberculosis (EPTB). This study aimed to explore the utility of inflammatory biomarkers from the dry blood spots (DBS) as a tool for monitoring treatment response in EPTB. In a prospective cohort study, 40 inflammatory biomarkers were investigated in DBS samples from 105 EPTB cases using a Luminex platform. The samples were taken before, and, at the end of the 2nd and 6th months of treatment. A total of 11 inflammatory host biomarkers changed significantly with treatment in all EPTB patients. CXCL9/MIG, CCL20, CCL23, CXCL10/IP-10, CXCL1, CXCL2, and CXCL8 significantly declined in our cohort of EPTB (48 TB pleuritis and 57 TB lymphadenitis) patients at both time points. A biosignature consisting of MIG, CCL23, and CXCL2, corresponded with the treatment response in 81% of patients in the 2nd month and 79% of patients at the end of treatment. MIG, CCL23, IP-10, and CXCL2 changed significantly with treatment in all patients including those showing partial clinical response at the 2nd month of treatment. The changes in the levels of inflammatory biomarkers in the DBS correspond with the treatment success and can be developed as a routine test in low-resource settings., (© 2023. The Author(s).)

Objectives: To assess the diagnostic accuracy of different cut-off values of pleural fluid adenosine deaminase levels as a diagnostic method for tuberculous pleural effusion., Methods: The prospective study was conducted from 2014 to 2016 at the Aga Khan University Hospital, Karachi, and comprised pleural fluid samples of adult patients with and without tuberculosis which were tested for adenosine deaminase levels, and divided into tuberculosis group A and non-tuberculosis group B. Sensitivity, specificity, negative predictive value and positive predictive value were calculated using different cut-offs. Data was analysed using IBM SPSS (Statistical Package for Social Sciences) version 21.0 (IBM Corp., Armonk, NY)., Results: Of 155 patients, 46(29.7%) had tuberculosis; 30(65.2%) males and 16(34.8%) females. Those who did not have tuberculosis were 109(70.3%); 69(63.3%) males and 40(36.7%) females. The adenosine deaminase levels were elevated in group A compared to group B (p<0.001). The cut-off of 30U/L showed the highest sensitivity (71.7%) and negative predictive value (87.4%), and a specificity of 82.6%. The cut-off of 50U/L showed the highest specificity (89.9%) with sensitivity 52.2%, and the cut-off of 40U/L showed the highest positive predictive value of 68.9% with sensitivity 67.4% and specificity 87.2%., Conclusions: Pleural fluid adenosine deaminase testing for diagnosing tuberculosis pleuritis revealed highest sensitivity and moderate specificity for cut-off value of 30U/L.

Introduction: The differential diagnosis of pleural effusion is difficult, and studies have reported on the potential role of adenosine deaminase (ADA) in the differential diagnosis of undiagnosed pleural effusion. This retrospective study aimed to investigate the diagnostic role of ADA in pleural effusion., Methods: 266 patients with pleural effusion from three centers were enrolled. The concentrations of ADA and lactate dehydrogenase (LDH) were measured in pleural fluids and serum samples of the patients. The diagnostic performance of ADA-based measurement for tuberculous pleural effusion (TPE), malignant pleural effusion (MPE), and parapneumonic effusion (PPE) was examined by receiver operating characteristic (ROC) curve analysis., Results: An area under the ROC curve (AUC) value of 0.909 was obtained using the pleural ADA values as the indicator for TPE identification (sensitivity: 87.50%, specificity: 87.82%). The ratio of serum LDH to pleural ADA (cancer ratio) provided the predictive capacity with an AUC of 0.879 for MPE diagnosis (sensitivity: 95.04%, specificity: 67.06%). At a cut-off value of 14.29, the pleural ADA/LDH ratio showed a sensitivity and specificity of 81.13% and 83.67%, respectively, and a high AUC value of 0.888 for the differential diagnosis of PPE from TPE., Conclusion: ADA-based measurement is helpful for the differential diagnosis of pleural effusion. Further studies should be performed to validate these results.

The diagnosis of pleural tuberculosis (TB) remains difficult due to the paucity of Mycobacterium tuberculosis in pleural fluid (PF). This study aimed to improve pleural TB diagnosis using highly sensitive digital PCR (dPCR) technique. A total of 310 patients with evidence of PF were consecutively enrolled, 183 of whom suffered from pleural TB and 127 from non-TB. PF samples were prospectively collected and total DNA was extracted. The copy numbers of M. tuberculosis insertion sequence (IS) 6110 and IS 1081 in DNA were quantified using dPCR. The overall area under the curve of IS 6110- dPCR was greater than that of IS 1081- dPCR (0.85 versus 0.79). PF IS 6110 OR IS 1081- dPCR (according to their cut-off values, "positive" was defined as either of them was positive, while "negative" was defined as both of them were negative) had higher sensitivity and equal specificity compared with single target-dPCR. The sensitivity of PF IS 6110 OR IS 1081- dPCR for total, definite, and probable pleural TB was 59.0% (95% CI = 51.5% to 66.2%), 72.8% (95% CI = 62.6% to 81.6%), and 45.1% (95% CI = 34.6% to 55.8%), respectively. Its specificity was 100% (95% CI = 97.1% to 100.0%). PF IS 6110 OR IS 1081- dPCR showed a higher sensitivity than smear microscopy (57.4% versus 7.1%), mycobacterial culture (55.3% versus 31.8%), and Xpert MTB/RIF (57.6% versus 23.0%). Long antituberculosis treatment time (>1 month) was found to be associated with negative dPCR results in pleural TB patients. This study indicates that PF IS 6110 OR IS 1081 -dPCR is an accurate molecular assay, which is more sensitive than routine etiological tests and has the potential to enhance the definite diagnosis of pleural TB. IMPORTANCE Pleural TB is one of the most frequent causes of pleural effusion, especially in areas with high burden of TB. Due to the paucibacillary nature of the disease, the diagnostic sensitivities of all available bacteriological and molecular tests remain poor. There is an urgent need to develop new efficient methods. Digital PCR (dPCR) is the third generation of PCR that enables the exact quantification of trace nucleic acids in samples. This study evaluates the diagnostic performance of pleural fluid (PF) dPCR analysis for pleural TB, and shows that PF IS 6110 OR IS 1081- dPCR has a higher sensitivity than routine etiological tests such as smear microscopy, mycobacterial culture, and Xpert MTB/RIF. This work provides a new choice for improving the definite diagnosis of pleural TB.

Background: Paediatric pleural tuberculosis (TB) is a paucibacillary disease, which increases the difficulty of examination. We aimed to assess the performance of pleural fluid adenosine deaminase (ADA) in the detection of paediatric pleural TB., Methods: PubMed, Web of Science Core Collection, Embase and Cochrane Library databases were searched up to 20 December 2021. We used the bivariate and hierarchical summary receiver operating characteristic models to compute pooled estimates for the overall diagnostic accuracy parameters of ADA for diagnosing paediatric pleural TB., Results: Eight studies, including 290 pleural fluid samples, met the inclusion criteria. The pooled sensitivity of ADA was 0.85 (95% CI: 0.78-0.90, I 2 : 55.63% < 75%) for detecting patients with paediatric pleural TB. A total of 262 pleural fluid samples from four studies were included to differentiate patients with paediatric pleural TB from controls. At a unified cut-off value of 40 U/L, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under the summary receiver operating characteristic curve of ADA were 0.89, 0.58, 2.09, 0.20, 10.48 and 0.89, respectively., Conclusions: At a cut-off value of 40 U/L, the overall performance of ADA was good for detecting paediatric pleural TB, with relatively high sensitivity and low specificity. Key messageAccurate identification of paediatric pleural TB will help eliminate TB in children. At a cut-off value of 40 U/L, the overall performance of ADA was good for detecting paediatric pleural TB, with relatively high sensitivity and low specificity.

Background: This study aimed to evaluate the diagnostic accuracy of pleural fluid (PF) lactate dehydrogenase (LDH) to adenosine deaminase (ADA) (LDH/ADA) ratio for tuberculous pleural effusion (TPE). Especially to explore whether the LDH/ADA ratio provides added diagnostic value to ADA., Methods: The diagnostic accuracy of PF LDH/ADA ratio and ADA for TPE was evaluated in two cohorts, named the BUFF (Biomarkers for patients with Undiagnosed pleural eFFusion) cohort (62 with TPE and 194 with non-TPE) and the SIMPLE (a Study Investigating Markers in PLeural Effusion) cohort (33 with TPE and 177 with non-TPE). Receiver operating characteristic (ROC) curve and decision curve were used to measure the diagnostic accuracy of the PF LDH/ADA ratio. The added diagnostic value of the LDH/ADA ratio to ADA was evaluated with net reclassification improvement (NRI) and integrated discrimination improvement (IDI)., Results: The area under the ROC curves (AUCs) of PF ADA and LDH/ADA ratio in the BUFF cohort were 0.76 and 0.74, respectively. In the SIMPLE cohort, the AUCs of PF ADA and LDH/ADA ratio were 0.80 and 0.85, respectively. The decision curves of PF LDH/ADA and ADA were close in both the BUFF and SIMPLE cohorts. The NRI and IDI analyses did not reveal any added diagnostic value of LDH/ADA to ADA., Conclusions: PF LDH/ADA ratio has moderate diagnostic accuracy for TPE. It does not provide added diagnostic value beyond ADA. The current evidence does not support LDH/ADA ratio for diagnosing TPE., (© 2022. The Author(s).)

Disseminated tuberculosis is a rare form of tuberculosis that can cause severe illness if diagnosed and treated late. We present the case of a young Senegalese woman who had a miscarriage due to a pelvic inflammatory disease, followed by the development of a left pleural effusion. Despite laparoscopic findings and a salpinx biopsy that revealed necrotizing granulomas, only microbiological examinations of pleural biopsies revealed the final diagnosis of disseminated, drug-sensitive tuberculosis.

Pleural effusion(PE) is a common medical problem with various causes. The differential diagnosis for PE is often challenging. This consensus was generated by members of the academic group of the pleural and mediastinal diseases(preparatory) of Chinese Thoracic Society and some external experts. The members convened in virtual meetings and conducted an extensive literature investigation and assessed the quality of the evidence using a modified grading of recommendations assessment, development, and evaluation(GRADE) approach. This consensus included three chapters: the initial evaluation of PE, the diagnosis of PE with common causes, and the diagnosis of PE with uncommon causes.The main recommendations of Chapter Ⅰ were as follows:(1) For patients suspected of PE according to medical history and clinical manifestations, thoracic CT or ultrasound is recommended to confirm the presence or absence of PE.(2) Ultrasound-guided thoracentesis is recommended when available. Recommended tests for all sampled pleural effeusions include total protein, lactate dehydrogenase (LDH), adenosine deaminase (ADA), differential cell count, and cytological examination.(3) It is recommended to use Light's criteria to distinguish exudate and transudate. When PE is classified to be exudates with heart failure, it is recommended to detect N-terminal pro-brain natriuretic peptide of PE or serum-pleural fluid albumin gradient to assist the judgment.(4) Pleural biopsy is recommended for patients for whom the causes of PE cannot be identified by the detection of PE samples, and CT or ultrasound-guided pleural biopsy is more accurate. Thoracoscopy is recommended for patients whose etiology cannot be identified by laboratory tests of PE and/or pleural biopsy histopathology.The main recommendations of Chapter Ⅱ were as follows:(1)It is suggested to obtain more samples or use immunocytochemistry to assist the diagnosis and cell typing when initial cytopathology examination shows atypical cells, suspicious malignant or malignant cells. (2) Liquid medium for Mycobacterium tuberculosis culture is recommended to improve the positive rate. Molecular diagnosis (nucleic acid amplification or Xpert MTB/RIF) is recommended when tuberculous PE is suspected. For suspected tuberculous PE where the examination of PE is inconclusive. CT or ultrasound-guided pleural biopsy or thoracoscopy is recommended to obtain pleural tissue for acid-fast staining, Mycobacterium tuberculosis nucleic acid amplification and culture.(3)C-reactive protein (CRP) of PE is recommended to distinguish uncomplicated PPE from complicated PPE. It is suggested to inoculate pleural effusion into blood culture bottles or culturing specimens from ultrasound-guided pleural biopsy to increase the positive rate.The main recommendations of Chapter Ⅲ were as follows:(1) It is recommended to comprehensively analyze the patients' medical history, clinical manifestations, effusion characteristics, and biopsy pathological results to indentify uncommon causes.(2) It is recommended to detect the presence of chylomicrons or cholesterol crystals, with testing of the levels of triglyceride and cholesterol in PE for clinical suspicion of chylothorax or pseudochylothorax. (3) PE may be the result of a combination of various causes, and it is recommended to screen factors such as heart failure, hypoalbuminemia, and thoracic infection for critical patients.(4) For patients with PE whose cause has not been identified by thoracoscopic pleural biopsy, close follow-up for at least 2 years is recommended to exclude malignant diseases.

Objective: This study aimed to describe the clinical and laboratory findings of patients diagnosed with pleural tuberculosis at two hospitals in southern Brazil., Methods: Patients aged < 18 years were evaluated retrospectively. The patients' medical and epidemiological history, tuberculin skin test results, radiological and pathological findings, and pleural fluid analysis results were retrieved., Results: Ninety-two patients with pleural tuberculosis were identified. The mean age was 10.9 years old. Twenty-one percent were children aged six years or less. The most common symptoms were fever (88%), cough (72%), and chest pain (70%). Unilateral pleural effusion was observed in 96% of the cases. Lymphocyte predominance was found in 90% of the pleural fluid samples. The adenosine deaminase activity of the pleural fluid was greater than 40 U/L in 85% of patients. A diagnosis of community-acquired pneumonia with antibiotic prescriptions was observed in 76% of the study population., Conclusions: Tuberculosis etiology must be considered in unilateral pleural effusion in a child with contact with a case of tuberculosis. Pleural fluid biomarkers contribute to the diagnosis of pleural tuberculosis in children and adolescents., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2022. Published by Elsevier Editora Ltda.)

Objective: The diagnostic performance of pleural fluid interleukins as potential biomarkers for tuberculous pleural effusion (TPE) remains unclear. We assessed the diagnostic accuracy of various interleukins in the pleural fluid for TPE and evaluated their ability to differentiate TPE from other effusions., Methods: We queried the PubMed and Embase databases for studies indexed till October 2021. We included studies that (a) provided information regarding sensitivity and specificity of pleural fluid interleukins for diagnosing TPE, or (b) compared pleural fluid interleukin levels between TPE and malignant or parapneumonic effusions. We used hierarchical summary receiver operating characteristic plots to model summary sensitivity and specificity. Random effects modeling was employed to pool standardized mean differences (SMD) across descriptive studies comparing TPE and other effusions., Results: We included 80 publications in our review; most were small and of poor quality. All interleukins except interleukin-27 (interleukins 1-beta, 2, 4, 6, 8, 10, 12, 12p40, 13, 18, 33) showed poor diagnostic accuracy and inconsistent discrimination of TPE from other effusions. The summary estimates for sensitivity, specificity, and diagnostic odds ratio were 0.94 (95 % CI 0.85-0.98), 0.97 (95 % CI 0.93-0.99), and 507.13 (95 % CI 130.66-1968.34) respectively for pleural fluid interleukin-27. Mean pleural fluid interleukin-27 levels in TPE were significantly higher than malignant (summary SMD 3.72, 95 % CI 2.81-4.63) or parapneumonic (summary SMD 2.45, 95 % CI -1.80-3.09) effusions., Conclusion: Pleural fluid interleukins are poor diagnostic biomarkers for TPE. Only pleural fluid interleukin-27 exhibited good accuracy in diagnosing TPE and needs further evaluation., 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 © 2022 Elsevier Ltd. All rights reserved.)

Pleural effusion (PE) is a common manifestation of tuberculosis (TB) and malignant tumors but tuberculous PE (TPE) is difficult to distinguish from malignant PE (MPE), especially by noninvasive detection indicators. This study aimed to find effective detection indices in blood and PE for differentiating TB from a malignant tumor. A total of 815 patients who were diagnosed with TB or cancer in Hubei Shiyan Taihe Hospital from 2014 to 2017 were collected. Amongst them, 717 were found to have PE by thoracoscopy. Clinical characteristics, patients' blood parameters and PE indicator information were summarized for analysis. Patients with MPE had higher percentages to be bloody and negative of Rivalta test in PE than those with TPE. For clinical indicators, comparison of the specific parameters in blood showed that 18 indicators were higher in the TPE group than in the MPE group. By contrast, 12 indicators were higher in the MPE group than in the TPE group (P < .01). In addition, in PE tests, 3 parameters were higher in the TPE group, whereas other 4 parameters were higher in the MPE group (P < .01). Then, for clinical diagnosing practice, ROC analysis and principal component analysis were applied. The top 6 relevant indicators with area under curve over 0.70 were screened out as follows: hydrothorax adenosine dehydrogenase (pADA, 0.90), hydrothorax high-sensitivity C reactive protein (0.79), percentage of blood monocyte (sMONp, 0.75), blood high-sensitivity C reactive protein (sHsCRP, 0.73), erythrocyte sedimentation rate (0.71) and blood D-dimer (0.70). Moreover, logistic regression model revealed that a specific combination of 3 biomarkers, namely, pADA, sMONp and sHsCRP, could enhance the distinguishment of TB from malignant tumor with PE (area under curve = 0.944, 95% confidence interval = 0.925-0.964). The diagnostic function of the top single marker pADA in patients from different groups was analyzed and it was found to maintain high specificity and sensitivity. The 6 indicators, namely, pADA, hydrothorax high-sensitivity C reactive protein, sMONp, sHsCRP, sESR and blood D-dimer, showed significant diagnostic value for clinicians. Further, the combination of pADA, sMONp and sHsCRP has high accuracy for differential diagnosis for the first time. Most interestingly, the single marker pADA maintained high specificity and sensitivity in patients with different statuses and thus has great value for rapid and accurate diagnosis of suspected cases., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Increased pleural fluid adenosine deaminase (ADA) is useful for diagnosing tuberculous pleurisy (TB), but high ADA levels are associated with other diseases. In this study, we compare various disease characteristics in patients with high-ADA pleural effusion., Methods: We retrospectively collected data for 456 patients with pleural fluid ADA levels of ≥ 40 U/L from January 2012 to October 2021. Cases were classified as TB (n = 203), pleural infection (n = 112), malignant pleural effusion (n = 63), nontuberculous mycobacteria (n = 22), malignant lymphoma (ML) (n = 18), autoimmune diseases (n = 11), and other diseases (n = 27), and data were compared among those diseases. Predictive factors were identified by comparing data for a target disease to those for all other diseases. A diagnostic flowchart for TB was developed based on those factors., Results: The most frequent disease was TB, though 60.0% of patients were diagnosed with other diseases. Median ADA levels in patients with TB were 83.1 U/L (interquartile range [IQR] 67.2-104.1), higher than those of patients with pleural infection (median 60.9 [IQR 45.3-108.0], p = 0.004), malignant pleural effusion (median 54.1 [IQR 44.8-66.7], p < 0.001), or autoimmune diseases (median 48.5 [IQR 45.9-58.2], p = 0.008), with no significant difference from NTM (p = 1.000) or ML (p = 1.000). Pleural fluid lactate dehydrogenase (LDH) levels of < 825 IU/L were beneficial for the diagnosis of TB. Neutrophil predominance or cell degeneration, white blood cell count of ≥ 9200/µL or C-reactive protein levels of ≥ 12 mg/dL helped in diagnosing pleural infection. Pleural fluid amylase levels of ≥ 75 U/L and a pleural fluid ADA/total protein (TP) ratio of < 14 helped in diagnosing malignant pleural effusion. High serum LDH and high serum/pleural fluid eosinophils helped in diagnosing ML and autoimmune diseases, respectively. The flowchart was comprised of the following three factors: pleural fluid LDH < 825 IU/L, pleural fluid ADA/TP of < 14, and neutrophil predominance or cell degeneration, which were decided by a decision tree. The diagnostic accuracy rate, sensitivity, and specificity for the diagnosis of TB were 80.9%, 78.8%, and 82.6%, respectively., Conclusion: Cases involving high pleural fluid ADA levels should be investigated using several factors to distinguish TB from other diseases., (© 2022. The Author(s).)

Background and Objectives: Tuberculous pleurisy is a common extrapulmonary TB that poses a health threat. However, diagnosis of TB pleurisy is challenging because of the low positivity rate of pleural effusion mycobacterial culture and difficulty in retrieval of optimal pleural tissue. This study aimed to investigate the efficacy of mycobacterial culture from pleural tissue, obtained by forceps biopsy through medical pleuroscopy, in the diagnosis of TB pleurisy. Materials and Methods: This study retrospectively enrolled 68 TB pleurisy patients. Among them, 46 patients received semi-rigid pleuroscopy from April 2016 to March 2021 in a tertiary hospital. We analyzed the mycobacterial culture from pleural tissue obtained by forceps biopsy. Results: The average age of the study participants was 62.8 years, and 64.7% of them were men. In the pleuroscopic group, the sensitivity of positive Mycobacterium tuberculosis (M. TB) cultures for sputum, pleural effusion, and pleural tissue were 35.7% (15/42), 34.8% (16/46), and 78.3% (18/23), respectively. High sensitivities of M. TB culture from pleural tissue were up to 94.4% and 91.7% when pleural characteristic patterns showed adhesion lesions and both adhesion lesions and presence of micronodules, respectively. Conclusions: M. TB culture from pleural tissue should be considered a routine test when facing unknown pleural effusion during pleuroscopic examination.

Adenosine deaminase 2 (ADA 2 ) is reported as a novel diagnostic biomarker for tuberculous pleural effusion (TPE) in many studies. This meta-analysis was conducted to systematically evaluate the general diagnostic performance of pleural ADA 2 in TPE. After searching for relevant studies that investigated the diagnostic performance of pleural ADA 2 in TPE in several databases, we assessed and selected eligible studies to calculate pooled parameters by STATA 16.0 software. A final set of thirteen studies entirely met the inclusion standards and were used to calculate pooled parameters in our meta-analysis. Among them, there were nine English studies and four Chinese studies. The pooled parameters of pleural ADA 2 in diagnosing TPE were summarized as follows: sensitivity, 0.91 (95% CI: 0.86-0.95); specificity, 0.93 (95% CI: 0.92-0.95); positive likelihood ratio, 13.9 (95% CI: 10.6-18.3); negative likelihood ratio, 0.09 (95% CI:0.06-0.16); diagnostic odds ratio, 147 (95% CI: 76-284); and the area under the curve, 0.95 (95% CI: 0.93-0.97). Pleural ADA 2 is a reliable indicator with excellent accuracy in TPE diagnosis. However, we need to combine pleural ADA 2 with diverse examinations to diagnose TPE in clinical practice., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Tingting Zeng et al.)

Background: Due to the low efficiency of a single clinical feature or laboratory variable in the diagnosis of tuberculous pleural effusion (TBPE), the diagnosis of TBPE is still challenging. This study aimed to build a scoring diagnostic model based on laboratory variables and clinical features to differentiate TBPE from non-tuberculous pleural effusion (non-TBPE)., Methods: A retrospective study of 125 patients (63 with TBPE; 62 with non-TBPE) was undertaken. Univariate analysis was used to select the laboratory and clinical variables relevant to the model composition. The statistically different variables were selected to undergo binary logistic regression. Variables B coefficients were used to define a numerical score to calculate a scoring model. A receiver operating characteristic (ROC) curve was used to calculate the best cut-off value and evaluate the performance of the model. Finally, we add a validation cohort to verify the model., Results: Six variables were selected in the scoring model: Age ≤ 46 years old (4.96 points), Male (2.44 points), No cancer (3.19 points), Positive T-cell Spot (T-SPOT) results (4.69 points), Adenosine Deaminase (ADA) ≥ 24.5U/L (2.48 point), C-reactive Protein (CRP) ≥ 52.8 mg/L (1.84 points). With a cut-off value of a total score of 11.038 points, the scoring model's sensitivity, specificity, and accuracy were 93.7%, 96.8%, and 99.2%, respectively. And the validation cohort confirms the model with the sensitivity, specificity, and accuracy of 92.9%, 93.3%, and 93.1%, respectively., Conclusion: The scoring model can be used in differentiating TBPE from non-TBPE., (© 2022. The Author(s).)

Accurate differential diagnosis is the key to choosing the correct treatment for pleural effusion. The present study aimed to assess whether interleukin 32 (IL-32) could be a new biomarker of tuberculous pleural effusion (TPE) and to explore the biological role of IL-32 in TPE. IL-32 levels were evaluated in the pleural effusions of 131 patients with undetermined pleural effusion from Wuhan and Beijing cohorts using an enzyme-linked immunosorbent assay method. Macrophages from TPE patients were transfected with IL-32-specific small interfering RNA (siRNA), and adenosine deaminase (ADA) expression was determined by real-time PCR and colorimetric methods. With a cutoff value of 247.9 ng/mL, the area under the curve of the receiver operating characteristic (ROC) curve for IL-32 was 0.933 for TPE, and the sensitivity and specificity were 88.4% and 93.4%, respectively. A multivariate logistic regression model with relatively good diagnostic performance was established. IL-32-specific siRNA downregulated ADA expression in macrophages, and IL-32γ treatment significantly induced ADA expression. Our results indicate that IL-32 in pleural effusion may be a novel biomarker for identifying patients with TPE. In addition, our multivariate model is acceptable to rule in or rule out TPE across diverse prevalence settings. Furthermore, IL-32 may modulate ADA expression in the tuberculosis microenvironment. (This study has been registered at ChiCTR under registration number ChiCTR2100051112 [https://www.chictr.org.cn/index.aspx].) IMPORTANCE Tuberculous pleural effusion (TPE) is a common form of extrapulmonary tuberculosis, with manifestations ranging from benign effusion with spontaneous absorption to effusion with pleural thickening, empyema, and even fibrosis, which can lead to a lasting impairment of lung function. Therefore, it is of great significance to find a rapid method to establish early diagnosis and apply antituberculosis therapy in the early stage. This study indicates that interleukin 32 (IL-32) in pleural effusion is a new high-potency marker to distinguish TPE from pleural effusions with other etiologies. A multivariate model combining age, adenosine deaminase (ADA), lactic dehydrogenase, and IL-32 may reliably rule in TPE in intermediate- or high-prevalence areas. Additionally, we observed that IL-32 might regulate ADA expression in macrophages in the tuberculosis microenvironment. Therefore, this study provides new insights into the role of IL-32 in the tuberculosis microenvironment.

Tuberculous pleurisy (TP) is a common type of extrapulmonary tuberculosis (EPTB). With the development of research and changes in TP patient characteristics, an increasing number of studies have revealed the prevalence, risk factors, and novel diagnosis techniques. Thus, this bibliometric analysis was performed to identify global scientific output characteristics and research hotspots and frontiers for TP over the past 15 years. We searched the Web of Science Core Collection (WoSCC) Science Citation Index Expanded (SCI-expanded) for literature published between 2007 and 2021 and recorded their information. The Bibliometrix software package was used for bibliometric indicator analysis, and VOSviewer was used to visualize the trends of and hotspots in TP research. A total of 1,464 original articles were reviewed, and the results indicated that the annual number of publications (Np) focusing on TP has increased over the past 15 years. China had the largest number of papers and the highest H-index, and the United States ranked first for number of citations (Nc). EGYPTIAN KNOWLEDGE BANK and PLOS ONE were the most prolific unit and journal, respectively. The use of the Xpert assay and immune-related biomarker detection to diagnose TP appears to be a recent research hotspot. This bibliometric study demonstrated that the number of publications related to TP have tended to increase. China is a major producer, and the United States is an influential country in this field. Research in the past 15 years has been predominantly clinical research. The diagnosis of TP was the focus of research, and the exploration of novel diagnostic techniques, verification of diagnostic markers, and combination of diagnostic methods have been recent research hotspots. Immune-related biomarkers should be given more attention in the field of TP diagnosis., 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 © 2022 Bian, Deng, Zhang and Hou.)

Introduction: Pleural tuberculosis (TB) is the archetype of extrapulmonary TB (EPTB), which mainly affects the pleural space and leads to exudative pleural effusion. Diagnosis of pleural TB is a difficult task predominantly due to atypical clinical presentations and sparse bacillary load in clinical specimens., Area Covered: We reviewed the current literature on the globally existing conventional/latest modalities for diagnosing pleural TB. Bacteriological examination (smear/culture), tuberculin skin testing/interferon-γ release assays, biochemical testing, imaging and histopathological/cytological examination are the main modalities. Moreover, nucleic acid amplification tests (NAATs), i.e . loop-mediated isothermal amplification, PCR/multiplex-PCR, nested-PCR, real-time PCR and GeneXpert ® MTB/RIF are being utilized. Currently, GeneXpert Ultra, Truenat MTB TM , detection of circulating Mycobacterium tuberculosis ( Mtb ) cell-free DNA by NAATs, aptamer-linked immobilized sorbent assay and immuno-PCR (I-PCR) have also been exploited., Expert Opinion: Routine tests are not adequate for effective pleural TB diagnosis. The latest molecular/immunological tests as discussed above, and the other tools, i.e . real-time I-PCR/nanoparticle-based I-PCR and identification of Mtb biomarkers within urinary/serum extracellular vesicles being utilized for pulmonary TB and other EPTB types may also be explored to diagnose pleural TB. Reliable diagnosis and early therapy would reduce the serious complications associated with pleural TB, i.e . TB empyema, pleural fibrosis, etc.

Most of pleural effusions are caused by tuberculosis and malignant tumor. Difficult sampling and bacterial sparing nature of these diseases challenge doctors' diagnosis in China. This study aimed to develop a new convenient and effective method for the differentiation of tuberculous and malignant pleural effusion. A prospective cohort study of patients hospitalized with malignant (n = 90) and tuberculous (n = 130) pleural effusions from September 2018 to October 2020 was performed. The diagnostic performance of the age to pleural fluid ADA ratio (age/ADA) and other indicators to distinguish tuberculous and malignant pleural effusions was evaluated by receiver operating characteristic (ROC) curve analysis. The areas under the curve (AUC) of age/ADA and pleural fluid ADA were largest. Age/ADA showed sensitivity and specificity of 81.5% (95%CI 73.8%-87.8%) and 97.8% (95%CI 92.2%-99.7%) respectively. The sensitivity and specificity of pleural fluid ADA were 83.1% (95%CI 75.5%-89.1%) and 93.3% (95%CI 86.1%-97.5%) respectively. The positive likelihood [36.69 (95%CI 9.3-144.8)] of age/ADA was significantly higher than that of pleural fluid ADA [12.46 (95%CI 5.7-27.1)]. The AUCs for Cancer Ratio and Cancer Ratio plus were lower and showed a sensitivity of 80.0% (95%CI 72.1%-86.5%), 80.0% (95%CI 70.2%-87.7%) and a specificity of 81.5% (95%CI 73.8%-87.8%), 80.0% (95%CI 70.2%-87.7%) respectively. Age/ADA has a higher diagnostic accuracy than ADA. Age/ADA is a promising diagnostic index for tuberculous and malignant pleural effusion with high sensitivity and specificity, especially the high positive likelihood ratio. The diagnostic accuracy of Cancer Ratio and Cancer Ratio plus are inferior to those of age/ADA and ADA., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Tuberculous infection of T cell spot test (T-SPOT.TB) and adenosine deaminase (ADA) have a high diagnostic value in pleural effusion for tuberculous pleurisy. However, there were major differences in existing research in regard to the clinical application of the two trials. Therefore, we conducted a meta-analysis to systematically evaluate the diagnostic value of T-SPOT.TB and ADA., Methods: Pubmed, Web of Science and Embase databases were searched to compare diagnosis of tuberculous pleurisy by T-SPOT.TB and ADA. The search period was from inception to August 31, 2021. Statistical analyses were performed using Meta-disc 1.4, Revman 5.4 and Stata 16.0. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were determined. Summary receiver operating characteristic (SROC) curves and the area under the curve (AUC) were used to summarize overall diagnostic performance., Results: 10 qualified original research studies were included, with a total of 2075 patients, of which were 1391 tuberculous pleurisy and 684 non-tuberculous pleurisy. The pooled estimates of diagnostic accuracy of T-SPOT.TB were as follows: sensitivity, 0.88 (95% CI: 0.86-0.90; I 2  = 92.7%); specificity, 0.79 (95% CI: 0.76-0.82; I 2  = 93.7%); PLR, 4.49 (95% CI: 2.29-8.80; I 2  = 94.9%); NLR, 0.15 (95% CI: 0.08-0.30; I 2  = 94.3%), DOR, 35.72 (95% CI: 11.15-114.47; I 2  = 91.5%). The AUC for SROC was 0.9283 (95% CI: 0.8912-0.9654). The pooled estimates of diagnostic accuracy of ADA were as follows: sensitivity, 0.65 (95% CI: 0.62-0.67; I 2  = 98.2%); specificity, 0.90 (95% CI: 0.88-0.92; I 2  = 69.4%); PLR, 6.12 (95% CI: 4.71-7.96; I 2  = 11.9%); NLR, 0.33 (95% CI: 0.12-0.89; I 2  = 99.5%), DOR, 23.18 (95% CI: 12.75-42.14; I 2  = 66.7%). The AUC for SROC was 0.9208 (95% CI: 0.9029-0.9387)., Conclusion: Both T-SPOT.TB and ADA had high value in the diagnosis of tuberculous pleurisy. The sensitivity of T-SPOT.TB was higher than ADA, but the specificity of ADA was higher than T-SPOT.TB. On the whole, T-SPOT. TB had similar diagnostic accuracy to ADA., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Immune checkpoints are crucial for the maintenance of subtle balance between self-tolerance and effector immune responses, but the role of soluble immune checkpoints (sICs) in Mycobacterium tuberculosis (M. tb) infection remains unknown. We assessed the levels of multiple sICs in individuals with distinct M. tb infection status, and their dynamic changes during anti-tuberculosis treatment., Methods: We enrolled 24 patients with pulmonary tuberculosis, among which 10 patients were diagnosed with tuberculous pleurisy (TBP), 10 individuals with latent tuberculosis infection (LTBI), and 10 healthy volunteers from Wuxi Fifth People's Hospital and Huashan Hospital between February 2019 and May 2021. Plasma concentrations of thirteen sICs were measured at enrollment and during anti-tuberculosis treatment using luminex-based multiplex assay. sICs levels in tuberculous pleural effusion (TPE) and their relations to laboratory test markers of TPE were also assessed in TBP patients., Results: The circulating levels of sPD-1, sPD-L1, sCTLA-4, sBTLA, sGITR, sIDO, sCD28, sCD27 and s4-1BB were upregulated in tuberculosis patients than in healthy controls. A lower sPD-L1 level was found in LTBI individuals than in tuberculosis patients. In TBP patients, the levels of sPD-1, sPD-L2, sCD28, sCD80, sCD27, sTIM-3, sLAG-3, sBTLA, s4-1BB and sIDO increased significantly in TPE than in plasma. In TPE, sBTLA and sLAG-3 correlated positively with the adenosine deaminase level. sIDO and sCD80 correlated positively with the lactate dehydrogenase level and the percentage of lymphocytes in TPE, respectively. Meanwhile, sCD27 correlated negatively with the specific gravity and protein level in TPE. In tuberculosis patients, the circulating levels of sBTLA and sPD-L1 gradually declined during anti-tuberculosis treatment., Conclusions: We characterized the changing balance of sICs in M. tb infection. And our results revealed the relations of sICs to laboratory test markers and treatment responses in tuberculosis patients, indicating that certain sICs may serve as potential biomarkers for disease surveillance and prognosis of tuberculosis., (© 2022. The Author(s).)

Background: The differential diagnosis of tuberculous pleural effusion (TPE) and parapneumonic pleural effusion (PPE) is challenging due to similar clinical manifestations and body fluid biochemical profiles. Thyroid hormone levels change in response to lymphocyte proliferation in the peripheral blood of patients with mycobacterial infections such as tuberculosis; therefore, this study aimed to investigate the utility of assessing thyroid hormone levels to aid in the differential diagnosis of TPE and PPE., Methods: We measured free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) levels in the pleural effusions of 59 newly admitted patients (32 and 27 with TPE and PPE, respectively). Hormone levels were assessed using an electrochemiluminescence technique, and the diagnostic parameters for tuberculosis were evaluated. Differences in hormone levels between patients with TPE and PPE were assessed by t-tests, and their diagnostic value for a differential diagnosis was evaluated by receiver operating characteristic curve analyses., Results: FT3 and FT4 levels in patients with TPE were significantly higher than those in patients with PPE (p < 0.01 and p < 0.05, respectively), whereas TSH expression did not significantly differ between the two groups (p > 0.05). FT3 and FT4 levels showed no correlation with sex or history of smoking, although FT3 levels decreased with age. The highest sensitivity was observed for the quantification of FT3 levels (84.38%)., Conclusions: Increased FT3 and FT4 levels could potentially be used for the differential diagnosis of TPE and PPE., (Copyright © 2021 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background: Distinguishing tuberculous pleural effusion (TPE) from non-tuberculosis (TB) benign pleural effusion (BPE) remains to be a challenge in clinical practice. The aim of the present study was to develop and validate a novel nomogram for diagnosing TPE., Methods: In this retrospective analysis, a total of 909 consecutive patients with TPE and non-TB BPE from Ningbo First Hospital were divided into the training set and the internal validation set at a ratio of 7:3, respectively. The clinical and laboratory features were collected and analyzed by logistic regression analysis. A diagnostic model incorporating selected variables was developed and was externally validated in a cohort of 110 patients from another hospital., Results: Six variables including age, effusion lymphocyte, effusion adenosine deaminase (ADA), effusion lactatedehy drogenase (LDH), effusion LDH/effusion ADA, and serum white blood cell (WBC) were identified as valuable parameters used for developing a nomogram. The nomogram showed a good diagnostic performance in the training set. A novel scoring system was then established based on the nomogram to distinguish TPE from non-TB BPE. The scoring system showed good diagnostic performance in the training set [area under the curve (AUC) (95% confidence interval (CI)), 0.937 (0.917-0.957); sensitivity, 89.0%, and specificity, 89.5%], the internal validation set [AUC (95%CI), 0.934 (0.902-0.966); sensitivity, 88.7%, and specificity, 90.3%], and the external validation set [(AUC (95%CI), 0.941 (0.891-0.991); sensitivity, 93.6%, and specificity, 87.5%)], respectively., Conclusions: The study developed and validated a novel scoring system based on a nomogram originated from six clinical parameters. The novel scoring system showed a good diagnostic performance in distinguishing TPE from non-TB BPE and can be conveniently used in clinical settings., (© 2022. The Author(s).)

Background: The aim of this study was to evaluate the diagnostic accuracy of Xpert MTB/RIF Ultra (Xpert Ultra) and Xpert MTB/RIF (Xpert) for the diagnosis of tuberculous pleurisy (TBP) head-to-head using meta-analysis method., Methods: On May 12, 2021, we searched multiple databases for reports that used Xpert Ultra and Xpert for TBP diagnosis head-to-head and screened eligible studies for inclusion. Accuracy of Xpert Ultra and Xpert were compared to that of the composite reference standard (CRS) and culture. When heterogeneity was evident, sources of heterogeneity were explored using subgroup analyses, sensitivity analysis, and meta-regression analyses., Results: Five articles met the inclusion criteria for meta-analysis. When results from different specimens or different reference standards were reported in the same article, we analyzed them as separate studies. Thus, 6 studies compared Xpert Ultra and Xpert with CRS, 5 studies compared Xpert Ultra and Xpert with culture. Pooled sensitivity and specificity of Xpert Ultra were 52% and 98% compared to CRS, and 82% and 77% compared to culture. Pooled sensitivity and specificity of Xpert were 22% and 99% compared to CRS, and 48% and 94% compared to culture. Significant heterogeneity in sensitivity was observed compared to CRS., Conclusion: The sensitivity of Xpert Ultra was moderate but better than that of the Xpert; however, its specificity was lower. The role of Xpert Ultra and Xpert in the early and rapid diagnosis of TBP was limited., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

As the burden of tuberculosis (TB) in South Korea decreases while that of malignancy increases with an aging society, the composition of etiology for pleural effusion is changing. The aim of this study was to investigate the diagnostic value of adenosine deaminase (ADA) for diagnosis of tuberculous pleural effusion (TPE) in this circumstance. Medical records of patients who underwent medical thoracoscopy from May 2015 to September 2020 in Incheon St. Mary Hospital, Korea were retrospectively reviewed. TPE was diagnosed if one of the following criteria was met: (1) granuloma in pleura, (2) positive TB polymerase chain reaction or culture in pleural fluid or tissue with non-specific pathologic findings in pleura, or (3) bacteriologically confirmed pulmonary TB with non-specific pathologic findings in pleura. A total of 292 patients, including 156 with malignant pleural effusion (MPE), 52 with TPE, and 84 with other benign effusion, were analyzed. Among 206 patients with lymphocyte dominant pleural effusion, the area under receiver characteristic curve of ADA for diagnosis of TPE was 0.971. The sensitivity and specificity of a current cutoff value of 40 IU/L were 1.00 and 0.61, respectively, whereas those of a raised cutoff value of 70 IU/L were 0.93 and 0.93, respectively. Among 54 patients with ADA levels of 40-70 IU/L, 30 (55.6%) patients were diagnosed as MPE, 21 (38.9%) as other benign effusion, and only 3 (5.6%) as TPE. Caution is needed in clinical diagnosis of TPE with current ADA cutoff value in countries with decreasing TB incidence, due to many false positive cases., (© 2022. The Author(s).)

Exudative pleural effusion includes tuberculous pleural effusion (TPE), parapneumonic pleural effusion (PPE), and malignant pleural effusion (MPE). An elevated pleural fluid adenosine deaminase (ADA) typically implies TPE, but the rule may not apply to every individual case. Recent studies proposed that the pleural fluid lactate dehydrogenase (LDH)-to-ADA ratio showed a higher diagnostic power than pleural fluid ADA alone in differentiating the etiology of pleural effusion. Hence, we aimed to investigate the performance of pleural fluid LDH-to-ADA ratio as a biomarker in assistance with the diagnosis of TPE, PPE, and MPE. All patients who underwent thoracentesis for the first time with a pleural fluid ADA >40 U/L were included in this retrospective study. The clinical data including pleural fluid ADA and LDH-to-ADA ratio were analyzed. A total of 311 patients were enrolled during the study interval. The pleural fluid LDH-to-ADA ratio <14.2 (sensitivity: 74.2%; specificity: 90.4%) favored TPE, while the pleural fluid LDH-to-ADA ratio >14.5 (sensitivity: 79.9%; specificity: 78.5%) favored PPE. Besides, the pleural fluid LDH-to-ADA ratio >46.7 (sensitivity: 56.3%; specificity: 78.3%) favored MPE owing to primary lung cancers. In conclusion, the pleural fluid LDH-to-ADA ratio was an effective indicator in differentiating the etiology of pleural effusions in the cases of high ADA level in the pleural fluid., Competing Interests: None

Background: To explored the clinical, pathological, and bacteriological characteristics of pleural-based masses occurred during anti-tuberculosis (TB) treatment in patients with pleural TB., Methods: Patients referred with newly diagnosed pleural TB were prospectively enrolled into the study. Patients were followed up throughout the treatment, and clinical data were recorded. Percutaneous biopsy and surgical tissues from pleural-based masses were examined histologically and samples sent for PCR. Cytokines in the pleural effusions and clinical factors were collected and compared between different patients., Results: A total of 122 patients with pleural TB were enrolled, and 34.4% (42/122) displayed newly observed pleural-based mass during the treatment. Twelve cases underwent surgical resection at the 12 ± 0.5 months during the treatment course. Based on the surgical observation, 58.3% (7 /12) were located in pleura, 41.7% (5/12) were located in the lung parenchyma. Pathological observations showed that the pleural-based masses were typed as granulomatous inflammation, fibrous hyperplasia and necrosis. Mycobacterium tuberculosis PCR was positive in 57.1% of the cases (24/42). Any first-line anti-TB drug resistance gene mutations were positive in only 9.5% (4/42). Aside from 12 cases who underwent the surgical operation, 86.7% of the patients (26/30) still had a pleural-based mass at the end of 12 months treatment course. Patients with a pleural-based mass were younger, had a thicker pleural, a higher proportion of pleural adhesive, loculated pleural effusion and residual pleural effusion, and a higher level of LDH, ADA and lower glucose in pleural effusion than those without a pleural-based mass occurrence during the treatment (all Pcorr < 0.05)., Conclusions: Pleural-based masses were observed in about one-third of patients with pleural TB. The masses were in the lung or pleura and were divided into three pathological types., (© 2022. The Author(s).)

A 33-year-old woman with a fever, cough, and pharyngitis was admitted after left-sided pleural effusion was detected. The fever and upper respiratory symptoms were confirmed, and she was diagnosed with coronavirus disease (COVID-19) after showing a positive polymerase chain reaction (PCR) test. After thoracentesis, pleural fluid revealed elevated adenosine deaminase values and a positive QuantiFeron test; tuberculous pleurisy was thus suspected. Subsequent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR and anti-SARS-CoV-2 Spike IgG tests were negative, suggesting that the initial PCR result had been erroneous. However, we were unable to confirm this. Data concerning COVID-19 diagnostics are insufficient at present. It is important to make comprehensive judgments regarding the diagnosis and treatment of patients as well as public health.

To clarify the predominance of Th1 or Th2 immune responses in malignant and tuberculous pleural effusion (MPE and TPE, respectively), we performed a meta-analysis of previously published results of the levels of Th1/Th2 cytokines associated with these two types of pleural effusion to evaluate the use of Th1/Th2 cytokine profiles in distinguishing TPE from MPE. We searched the PubMed and EMBASE databases for studies indexed from 2000 to March 2021. We included studies that (a) diagnosed TPE and MPE based on culture or pleural tissue biopsy and that (b) compared levels of Th1/Th2 cytokines between TPE and MPE. Pooled data based on a random-effects model or fixed-effects model and standardized mean differences (SMDs) across studies were used to compare TPE and MPE. We also performed Egger's test to assess publication bias. Of 917 identified studies, a total of 42 studies were selected for the meta-analysis. Compared with MPE subjects, TPE subjects had a significantly higher level of TNF-α [2.22, (1.60-2.84)], an elevated level of IFN-γ [3.30, (2.57-4.40)] in pleural effusion, a situation where the Th1 immune response dominated. Conversely, the levels of interleukin-4 (IL-4) and IL-10 (Th2 cytokines) were higher in the MPE subjects than in the TPE subjects, showing statistically nonsignificant tiny effects [-0.15, (-0.94 to 0.63) and -0.04, (-0.21 to 0.12), respectively]. We confirmed that TPE, a situation in which the Th1 cytokines are predominant. The slight preponderance of Th2 cytokines in MPE, which is not convincing enough to prove., (© 2022. The Author(s).)

An 84-year-old woman visited our hospital for dyspnea due to right pleural effusion, with lymphocytic dominance and a high adenosine deaminase (ADA) level, that had been noted 1 month earlier. She was suspected of having tuberculosis pleurisy; however, anti-tuberculosis treatment yielded no improvements. She was diagnosed with pleural effusion due to primary Sjögren's syndrome (SjS) based on her dry eyes and mouth, positivity for anti-Sjögren's-syndrome-related antigen A/B, and histopathologic findings of a lip biopsy and thoracoscopic pleural biopsy. Her symptoms improved after starting steroid therapy. Cases of pleural effusion due to SjS with a high ADA level may be misdiagnosed as tuberculosis pleurisy.

Although there are several diagnostic modalities for tuberculous pleurisy, there is still a lack of easy, cost-effective, and rapid methods for confirming the diagnosis. In order to facilitate clinicians to diagnose patients with tuberculous pleurisy at an early stage, help patients to obtain treatment early, and reduce lung damage, it is hoped that new techniques will be available in the future to help diagnose tuberculous pleurisy rapidly in the clinic. To this end, this paper investigates the problem of bidirectional consistency based on event-triggered iterative learning. Firstly, a dynamic linearized data model of TB pleurisy intelligent system is established using compact-form dynamic linearization method, and a parameter estimation algorithm of TB pleurisy data model is proposed; then, based on this data model, an output observer and a dead zone controller are designed, and an event-triggered distributed model-free iterative learning bidirectional consistency control strategy is constructed by combining with signal graph theory. In this paper, 112 patients with pleural effusion were collected, including 76 patients with confirmed or clinically diagnosed tuberculous pleural effusion and 36 patients with nontuberculous pleural effusion. Pleural effusion T-SPOT.TB, blood T-SPOT.TB, pleural effusion Xpert MTB/RIF, and pleural effusion adenosine deaminase (ADA) tests were performed before treatment in the included patients. The sensitivity of pleural effusion T-SPOT.TB was higher than that of peripheral blood T-SPOT.TB (76.32%, 58/76), pleural effusion Xpert MTB/RIF (65.79%, 50/76), and pleural effusion ADA (28.95%, 22/76); the differences were statistically significant ( x 2  = 14.74, 25.22, and 76.45, P  < 0.01). The specificity of the Xpert MTB/RIF test for pleural effusion (100%, 36/36) was higher than that for pleural effusion T-SPOT.TB (77.78%, 28/36), peripheral blood T-SPOT.TB, and pleural effusion T-SPOT.TB. The sensitivity of the combined Xpert MTB/RIF test (64.47%, 49/76) was lower than that of the pleural effusion T-SPOT.TB alone (97.37%, 74/76)., Competing Interests: The authors declare that they have no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Suya Xi et al.)

Introduction:  The diagnosis of pleural tuberculosis remains a clinical challenge due to the paucibacillary nature of disease. Medical thoracoscopy remains the gold standard in diagnosing tuberculous pleuritis., Objective:  To establish the diagnostic yield of sago-seed thoracoscopic appearance of pleura in tuberculosis and its correlation with histopathology, tissue AFB culture and tissue Xpert MTB/Rif assay., Methods:  All consecutive patients with lymphocytic exudative pleural effusion, who fulfilled inclusion criteria of the study underwent medical thoracoscopy under local anesthesia and pleural tissue was sent for histopathology, AFB culture and Xpert MTB/Rif assay. Chronic granulomatous inflammation on histopathology and response to anti-tuberculous treatment was taken as reference standard for diagnosis of tuberculous pleurisy., Results:  A total of 249 patients were included in the study, out of which 168 had effusion secondary to tuberculosis. Sago-like nodules visualized on thoracoscopy had a sensitivity of 58.9 %, specificity of 92.6 % and diagnostic accuracy of 69.88 % for pleural tuberculosis. There is a strong association between the presence of sago-like nodules and detection of mycobacterium tuberculosis on Xpert MTB/Rif assay and AFB culture of pleura ( p -value 0.007)., Conclusion:  Sago seed nodules on pleura have a high positive predictive value for tuberculous pleurisy. In high endemic countries patients with this finding on thoracoscopy can be commenced on anti-tuberculous treatment before histopathology or culture results are available., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)