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Background: The association between tuberculous fibrosis and lung cancer development has been reported by some epidemiological and experimental studies; however, its underlying mechanisms remain unclear, and the role of macrophage (MФ) polarization in cancer progression is unknown. The aim of the present study was to investigate the role of M2 Arg-1 + MФ in tuberculous pleurisy-assisted tumorigenicity in vitro and in vivo., Methods: The interactions between tuberculous pleural effusion (TPE)-induced M2 Arg-1 + MФ and A549 lung cancer cells were evaluated. A murine model injected with cancer cells 2 weeks after Mycobacterium bovis bacillus Calmette-Guérin pleural infection was used to validate the involvement of tuberculous fibrosis to tumor invasion., Results: Increased CXCL9 and CXCL10 levels of TPE induced M2 Arg-1 + MФ polarization of murine bone marrow-derived MФ. TPE-induced M2 Arg-1 + MФ polarization facilitated lung cancer proliferation via autophagy signaling and E-cadherin signaling in vitro. An inhibitor of arginase-1 targeting M2 Arg-1 + MФ both in vitro and in vivo significantly reduced tuberculous fibrosis-induced metastatic potential of lung cancer and decreased autophagy signaling and E-cadherin expression., Conclusion: Tuberculous pleural fibrosis induces M2 Arg-1 + polarization, and M2 Arg-1 + MФ contribute to lung cancer metastasis via autophagy and E-cadherin signaling. Therefore, M2 Arg-1 + tumor associated MФ may be a novel therapeutic target for tuberculous fibrosis-induced lung cancer progression., (© 2024. The Author(s).)

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.)

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.

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.)

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.

Objective: To compare the clinical efficacy and adverse drug reactions of four different schemes in the treatment of pleural tuberculoma., Methods: A total of 120 patients with pleural tuberculoma admitted to the Tuberculosis Department of our hospital from January 2018 to January 2021 were selected as the research subjects. According to different treatment methods, the patients were divided into four groups, with 30 cases in each group. They were as follows: group A received classical HRZE regimen, group B received HRZE+pleural injection, group C received HZE+rifabutin, and group D received HZE+rifabutin+pleural injection. All patients were treated intensively for 3 months and then consolidated treatment for 6 months according to the patient's condition. The absorption of lesions in the four groups at different time was compared, and the occurrences of adverse drug reactions and treatment outcomes during treatment were recorded., Results: After 3 months of treatment, compared with groups A, B, and C, the number of significantly absorbed cases and effective cases in group D increased, while the number of invalid cases decreased. However, there was no statistical significance in the absorption of lesions between the four groups ( χ 2 = 8.272, P = 0.507). In addition, pairwise comparison showed no significant difference in the absorption of lesions ( P > 0.05). After 9 months of treatment, there was no significant difference in the absorption of lesions among the four groups ( χ 2 = 8.795, P = 0.185), but the absorption of lesions in group D was significantly better than that in group A ( P < 0.05). During treatment, the incidence of adverse reactions in the four groups was significantly different ( χ 2 = 8.779, P = 0.032). Pairwise comparison showed that the incidence of adverse reactions in groups C and D was significantly lower than that in group A ( P < 0.05). The total treatment course of group A was 9-16 months, and 10 cases (33.33%) still had residual lesions or pleural thickening at the end of treatment. The total course of treatment in group B was 9-12 months, and 7 cases (23.33%) still had residual lesions or pleural thickening at the end of the course of treatment. The total treatment course of group C was 9-16 months, and 8 cases (26.67%) still had residual lesions or pleural thickening at the end of treatment. The total course of treatment in group D was 9-12months, and there were still 2 cases of residual lesions (6.67%) at the end of the course., Conclusions: HZE+rifabutin+pleural injection against tuberculosis therapy has a significant clinical efficacy in the treatment of pleural tuberculoma, which can more effectively improve the clinical symptoms of patients, improve the efficacy, and reduce complications, with a good prognosis, worthy of clinical promotion., Competing Interests: The authors declare no competing interests., (Copyright © 2022 Xiaoling Zhang and Jingyu Chi.)

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).)

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.)

Background: Tuberculous pleural effusion (TPE) is one of the most common forms of extrapulmonary tuberculosis (Tb). Patients with TPE or malignant pleural effusions (MPE) frequently have a similar lymphocytic pleural fluid profile. Since the etiology of PE in various diseases is different, identifying the cellular components may provide diagnostic clues for understanding the pathogenesis., Objective: We determined the frequency of T helper (Th) subtypes in the PEs for differentiation of Tb and non-Tb patients., Methods: Thirty patients with TPE, 30 patients with MPE, 14 patients with empyema (EMP), and 14 patients with parapneumonic effusion (PPE) were enrolled between December 2018 and December 2019. Five-milliliter fresh PE in tubes containing heparin as an anticoagulant was obtained from patients. The frequencies of CD4+IL-9+, CD4+IL-22+, CD+IL-17+, and regulatory T-cells CD4+CD25+ FOXP3+ (Treg) were determined by flow cytometry., Results: Treg cells have a lower frequency in TPE patients [4.2 (0.362-17.24)] compared with non-TPE patients [26.3 (3.349-76.93, p < 0.0001)]. The frequency of CD4+IL-9+ cells was significantly lower in TPE patients [3.67 (0.87-47.83)] compared with non-TPE groups [13.05 (1.67-61.45), p < 0.0001]. On the contrary, there was no significant difference in the frequency of CD4+IL-17+ and CD4+IL-22+ cells between TPE and non-TPE patients (p = 0.906 and p = 0.2188). Receiver-operator curve (ROC) analysis demonstrated that CD4+CD25+FOXP3+ T cells [optimal cutoff value = 13.6 (%), sensitivity 90%, specificity 75.86%] could be considered as predictor for TPE. However, adenosine deaminase [cutoff value 27.5 (IU/l), sensitivity 90%, specificity 96.5%] levels had an even greater predictive capacity., Conclusion: ADA, Treg cells, and CD4+IL-9+ cells may differentiate TPE from non-TPE patients. However, these results need validation in an independent large cohort., 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 © 2021 Roofchayee, Adcock, Marjani, Dezfuli, Varahram, Garssen and Mortaz.)

Objective: Tuberculous pleurisy (TP) is a common disease of extrapulmonary tuberculosis, but its diagnosis is challenging. Recently, studies have found that the pleural fluid interferon gamma release assay (PF-IGRA) has important diagnostic value in TP, but the sample size of these studies was small, and the conclusions were inconsistent. Therefore, this study evaluated the diagnostic value of PF-IGRA in TP through a meta-analysis., Methods: We conducted a literature search in multiple databases to identify studies and calculated the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), summary receiver operating characteristic (SROC) curve and area under the curve (AUC)., Results: All 26 publications, including 30 case-control studies, were eventually included in the meta-analysis. The results showed that the pooled sensitivity, specificity, PLR, NLR, DOR and AUC with their 95% confidence intervals were 0.90 (0.88-0.91), 0.87 (0.85-0.89), 7.64 (4.46-13.07), 0.13 (0.09-0.19), 65.45 (32.13-133.33) and 0.9508, respectively. The subgroup analysis suggested that the sensitivity, specificity and AUC of PF-IGRA for TP in areas with a high tuberculosis burden were significantly higher than those in areas with a low tuberculosis burden. The sensitivity and AUC of the enzyme-linked immunosorbent assay method were higher than those of the enzyme-linked immunosorbent assay method for IGRA, but the specificity was similar. More importantly, PF-IGRA combined with adenosine deaminase (ADA) could increase the diagnostic value of TP., Conclusions: The current meta-analysis indicated that PF-IGRA has high diagnostic value in diagnosing TP, especially in areas with a high TB burden. We recommended that the combination of PF-IGRA and ADA is the best way to diagnose TP., (© 2021 John Wiley & Sons Ltd.)

Background: Until now, the influential factors associated with pleural adenosine deaminase (ADA) activity among children remain unclear. This retrospective study was therefore conducted aiming to investigate the factors associated with negative pleural ADA results in the diagnosis of childhood pleural tuberculosis (TB)., Methods: Between January 2006 and December 2019, children patients with definite or possible pleural TB were recruited for potential analysis. Then, patients were stratified into two categories: negative pleural ADA results group (experimental group, ≤40 U/L) and positive pleural ADA results group (control group, > 40 U/L). Univariate and multivariate logistic regression analyses were performed to estimate risk factors for negative pleural ADA results., Results: A total of 84 patients with pleural TB were recruited and subsequently classified as experimental (n = 17) and control groups (n = 67). Multivariate analysis (Hosmer-Lemeshow goodness-of-fit test: χ 2  = 1.881, df = 6, P = 0.930) revealed that variables, such as chest pain (age-adjusted OR = 0.0510, 95% CI: 0.004, 0.583), pleural total protein (≤45.3 g/L, age-adjusted OR = 27.7, 95% CI: 2.5, 307.7), pleural lactate dehydrogenase (LDH, ≤505 U/L, age-adjusted OR = 59.9, 95% CI: 4.2, 857.2) and blood urea nitrogen (≤3.2 mmol/L, age-adjusted OR = 32.0, 95% CI: 2.4, 426.9), were associated with negative pleural ADA results when diagnosing childhood pleural TB., Conclusion: Our findings demonstrated that chest pain, pleural total protein, pleural LDH, and blood urea nitrogen were associated with a negative pleural ADA result for the diagnosis of pleural TB among children. When interpreting pleural ADA levels in children with these characteristics, a careful clinical assessment is required for the pleural TB diagnosis.

Lung cancer patients with malignant pleural effusions (MPE) have a particular poor prognosis. It is crucial to distinguish MPE from benign pleural effusion (BPE). The present study aims to develop a rapid, convenient and economical diagnostic method based on FTIR near-infrared spectroscopy (NIRS) combined with machine learning strategy for clinical pleural effusion classification. NIRS spectra were recorded for 47 MPE samples and 35 BPE samples. The sample data were randomly divided into train set (n = 62) and test set (n = 20). Partial least squares, random forest, support vector machine (SVM), and gradient boosting machine models were trained, and subsequent predictive performance were predicted on the test set. Besides the whole spectra used in modeling, selected features using SVM recursive feature elimination algorithm were also investigated in modeling. Among those models, NIRS combined with SVM showed the best predictive performance (accuracy: 1.0, kappa: 1.0, and AUC ROC : 1.0). SVM with the top 50 feature wavenumbers also displayed a high predictive performance (accuracy: 0.95, kappa: 0.89, AUC ROC : 0.99). Our study revealed that the combination of NIRS and machine learning is an innovative, rapid, and convenient method for clinical pleural effusion classification, and worth further evaluation.

Introduction: To evaluate the performance of Xpert MTB/RIF Ultra (Xpert-Ultra) in testing pleural tissue and fluid collected by medical thoracoscopy among patients with unexplained exudative pleural effusion., Methods: Patients with an undiagnosed exudative pleural effusion were prospectively and consecutively recruited. Pleural tissue and fluid were collected by medical thoracoscopy and subjected to culture, Xpert MTB/RIF (Xpert) and Xpert-Ultra assays. Histopathological examination was also performed with the tissue and used as the major reference., Results: Sixty-one patients were enrolled, including: 27 tuberculosis (TB) pleurisy, 15 malignancy and 19 other chronic infection cases. The sensitivity, specificity, positive predictive value, and negative predictive value of Xpert-Ultra for TB diagnosis were 85.19% (23/27), 97.06% (33/34), 95.83% (23/24), and 89.19% (33/37), respectively. Xpert-Ultra testing with the biopsy tissue alone had an equivalent diagnostic capacity to that of pathological examination for the diagnosis of confirmed TB cases. By combining the pathological examination with Xpert-Ultra for biopsy, the percentage of confirmed TB cases greatly increased (i.e. 92.59% (25/27)). The "trace" positive outcome of Xpert-Ultra was highly supportive of TB diagnosis for both biopsy tissue and pleural fluid examinations., Conclusion: With the specimens collected by medical thoracoscopy, the Xpert-Ultra assay presented high value in identifying TB among pleurisy patients who had difficulties in etiological diagnosis., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Surgical intervention use is common in the management of childhood pleural tuberculosis (TB), however, its associated risk factors remain unclear. Between January 2006 and December 2019, consecutive children patients (≤ 15 years old) who had a diagnosis of pleural TB were included for the analysis. Surgical intervention was defined as debridement (such as breaking loculations), decortication, and thoracic surgery (such as lobectomy or segmental resection). Patients undergoing surgery were included as surgical group, without surgery were classified as non-surgical group, surgical risk factors were then estimated. Univariate and multivariate logistic regression analysis were performed to evaluate the risk factors for surgical interventions. A total of 154 children diagnosed as pleural TB (definite, 123 cases; possible, 31 cases) were included in our study. Of them, 29 patients (18.8%) were classified as surgical group and 125 patients (81.2%) were classified as non-surgical group. Surgical treatments were analyzed in 29 (18.8%) patients, including debridement (n = 4), decortication (n = 21), and thoracic surgery (n = 4). Further multivariate analysis revealed that empyema (age- and sex-adjusted OR = 27.3, 95% CI 8.6, 87.1; P < 0.001) and frequency of hospitalization (age- and sex-adjusted OR = 1.53, 95% CI 1.11, 2.11; P < 0.01) were associated with the use of surgical interventions in children with pleural TB. In China, surgical interventions are still required in a significant proportion of children with pleural TB, and the surgical risk is found to be associated with the frequency of hospitalization and empyema. These findings may be helpful to improve the management of children with pleural TB and minimize the risk of poor outcomes.

Background: Ethiopia reported a high rate of extra-pulmonary tuberculosis (EPTB) and the cases are increasing since the last three decades. However, diagnostic evidence to initiate TB treatment among EPTB cases is not well known. Therefore, we described the epidemiology and assessed how EPTB is diagnosed in a teaching hospital in Ethiopia., Methods: We conducted a retrospective review among all adult EPTB cases diagnosed in Yekatit 12 Hospital Medical College from 2015 to 2019. Using a standardized data abstraction sheet, we collected data from patients' medical records on sociodemographic, sites, and laboratory diagnosis of EPTB cases., Results: Of the 965 total TB cases, 49.8%(481) had a recorded diagnosis of EPTB during the study period. The mean age of EPTB patients was 32.9 years (SD±13.9) and 50.7% were males. Tubercular lymphadenitis (40.3%), abdominal (23.4%), and pleural TB(13.5%) were the most common sites of EPTB involvement, followed in descending order by the genitourinary, skeletal, central nervous system, abscess, breast, and laryngeal TB. We found a histopathology finding consistent with EPTB in 59.1% of cases, Acid-fast bacilli positive in 1.5%, and the rest diagnosed on radiological grounds. In the majority of cases, more than one diagnostic method was used to diagnose EPTB cases., Conclusions: Nearly half of TB patients had a recorded diagnosis of EPTB that comprise heterogeneous anatomical sites. All EPTB patients were started anti-TB therapy without definitive microbiology results. This indicates the diagnostic challenge of EPTB faced in our setting and proves to be significant for TB control in Ethiopia., Competing Interests: The authors have declared that no competing interests exist.

Aims: The present study was conceived to evaluate multi-targeted loop mediated amplification (MLAMP) for the rapid diagnosis of extrapulmonary tuberculosis (EPTB)., Methods and Results: A total of 700 patients were included who were classified into 2 groups: Group 1 (n = 400) included a 100 culture confirmed EPTB patients and 300 culture negative, suspected EPTB patients. Group 2 (n = 300) included negative controls from non-tubercular patients. All samples were subjected to Ziehl-Neelsen microscopy, solid culture on Lowenstein Jensen media, Polymerase chain reaction (PCR) targeting IS6110 gene and LAMP targeting both IS6110 and MPB64 individually and as MLAMP. The overall sensitivity of microscopy, culture, IS6110 PCR, IS6110 LAMP, MPB64 LAMP and the MLAMP assay were 12%, 25%, 72.5%, 80% and 86.6% respectively and the specificity of all the tests was 100%., Conclusion: MLAMP is a rapid robust tool for the diagnosis of EPTB and utilizing two targets for M. tuberculosis can improve the overall sensitivity and increase the yield of detection from extrapulmonary samples. The rapidity, ease of performance and low cost make MLAMP an excellent alternative in low-income, resource limited settings., Competing Interests: Conflicts of interest All authors have none to declare., (Copyright © 2020 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Introduction: The yield of mycobacteria is shown to be very low in pleural effusions as it is a pauci-bacillary disease. The present study looked at the yield of mycobacterium tuberculosis (MTB) in terms of GeneXpert for acid fast bacilli (AFB) and culture using a medical thoracoscopy guided biopsy and analysed whether the yield increases in more complicated effusions., Materials and Methods: This is a retrospective analysis of patients who underwent medical thoracoscopy for tubercular pleural effusions at our institute over the last 5-years. Patients who had no or minimal thin septations were considered as simple effusions and were subjected to semi-rigid thoracoscopy (n = 61). While patients who had multiple loculations and thick septations were considered as complicated effusions and were subjected to rigid thoracoscopy (n = 64). We considered granuloma on a biopsy as the standard for diagnosis of Tuberculosis (TB). Xpert MTB/RIF and The BACTEC MGIT was used for culture., Results: Out 125 patients with granulomatous inflammation on biopsy, 56 (44.8%) were positive for either GeneXpert or culture for MTB. Only GeneXpert was positive in 43 and only culture was positive in 13. Amongst 61 patients with simple effusion, 14 had either GeneXpert for AFB or AFB culture being positive and 9 out of these patients had GeneXpert for MTB detected on biopsy sample. Only culture was positive in 5 patients. In complicated pleural effusion group either GeneXpert or culture for mycobacterium was positive in 42 (65.6%) out of 64 patients. Only GeneXpert was positive in 34 and culture alone was positive in 8 patients., Conclusion: The yield of MTB increases as the pleural effusion becomes more complicated. GeneXpert in a biopsy sample is a useful marker for MTB yield especially in a complicated effusion., Competing Interests: Declaration of competing interest All authors have none to declare., (Copyright © 2020 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Pleural effusion adenosine deaminase (ADA) levels are elevated in various diseases. We investigated whether pleural effusion ADA levels differ among patients with malignant pleural mesothelioma (MPM), lung cancer (LC), and benign diseases, including tuberculous pleurisy. We examined 329 patients from February 2002 to July 2013. There were 131 MPM cases with ADA levels of 32.29 IU/L; 117 LC cases with ADA levels of 21.12 IU/L; 54 benign disease cases with ADA levels of 20.98 IU/L. A significant difference existed in pleural effusion ADA levels between MPM and benign disease patients. Pleural effusion ADA levels were significantly higher in MPM patients.

Background: Patients with undiagnostic pleural effusions are routinely examined by conventional medical thoracoscopy under the white light (WL). The endoscopic appearance of pleural diseases under WL could be misleading. Narrow-Band Imaging (NBI) has been applied as an interesting and effective diagnostic tool for endoscopy. However, there is also controversy about its value in the application of thoracoscopy., Objective: The objective of this study was to investigate the diagnostic value of NBI technology during thoracoscopy., Methods: Patients with undiagnosed pleural effusions admitted to our hospital between September 2017 and September 2019 were enrolled. During the thoracoscopy, we performed WL mode first and then NBI. Pictures of endoscopic real-time lesions were recorded under two modes, and at least five pieces of tissue were taken, respectively, on pleura lesions. Biopsy specimens were respectively taken for pathologic analysis. Diagnostic sensitivity, specificity were calculated to compare with pathologic results., Results: 100 eligible patients were enrolled, including 63 with malignancy, 23 with tuberculous pleurisy, 3 with systemic disease and 11 with the negative condition. Compared with pathological results, the sensitivity of WL was 91.01%, and NBI 84.27%; while the specificity of WL was 27.27%, and NBI 81.82%. Compared NBI with WL, the former's specificity is superior to the latter's, which is statistically significant (P < 0.05)., Conclusions: The advantage of NBI lies in its high specificity. It's useful to diagnose unknown pleural effusions in clinical practice. With better visualization of blood vessels, we can enhance the accuracy of biopsy and reduce the risk of unexpected bleeding arose from the biopsy.

Given the role of host defense peptides (HDPs) in the defensive response against mycobacteria, we analyzed the circulating levels of LL-37, β-defensin-2 and -3 in newly diagnosed patients with pulmonary (PTB) or pleural tuberculosis (PLTB) in whom measurements of pleural fluids were also performed. Severe PTB patients displayed higher circulating amounts of β-defensin-3, statistically different from controls, further decreasing upon antimycobacterial treatment. LL-37 concentrations appeared within the normal range at diagnosis, but tended to increase during treatment, becoming statistically upon its completion in moderate cases. PLTB patients revealed decreased levels of β-defensin-2 in presence of increased amounts of β-defensin-3 and LL-37; in their plasma or pleural fluids. Considering the immune-endocrine dysregulation of tuberculosis, we also performed correlation analysis detecting positive associations between levels of cortisol, IL-6 and β-defensin-3 in plasma from untreated severe patients as did their dehydroepiandrosterone and LL-37 values. Increased presence of β-defensins, may represent an attempt to improve defensive mechanisms; which also take part in the inflammatory reaction accompanying TB, reinforced by the association with immune-endocrine mediators. The divergent profile of PLTB patients, decreased β-defensin-2 but increased β-defensin-3 and LL-37 levels, suggests a differential role of these HDPs in a situation characterized for its better protective response., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Tuberculous empyema (TE) is associated with high mortality and morbidity. In the retrospective cohort study, we aimed to find risk factors for TE among pleural tuberculosis (TB) patients. Between July 2011 and September 2015, all culture-confirmed pleural TB patients (474 cases) were enrolled in our study. Empyema was defined as grossly purulent pleural fluid. Demographic and epidemiological data were collected for further analysis. Multivariate logistic regression analysis was used to evaluate risk factors of TE in pleural TB, age-adjusted odds ratio (OR) and 95% confidence interval (CI) were calculated to show the risk. The mean age was 35.7 ± 18.1 years old, males comprised 79.1% of the participants (375 cases). Forty-seven patients (9.9%) were multidrug-resistant TB (MDR-TB), 29 (6.1%) had retreatment TB, 26 (5.5%) had diabetes mellitus. The percentage of empyema patients was 8.9% (42 cases). Multivariate analysis revealed that male (adjusted OR = 4.431, 95% CI: 1.411, 13.919), pleural adenosine deaminase (ADA, >88 U/L) (adjusted OR = 3.367, 95% CI: 1.533, 7.395) and white blood cell (WBC, >9.52 10 9 /L) (adjusted OR = 5.763, 95% CI: 2.473, 13.431) were significant risk factors for empyema in pleural TB, while pulmonary TB (adjusted OR = 0.155, 95% CI: 0.072, 0.336) was the protective factor for the patients. TE remains a serious threat to public health in China. Male sex is a significant risk factor for TE while the presence of pulmonary TB is protective, and high levels of pleural ADA and WBC count could aid in early diagnosis of TE. This finding would help towards reducing the mortality and morbidity associated with TE.

For undiagnosed pleural effusion, diagnostic yields and safety were similar between pleuroscopic cryobiopsy and forceps biopsy, but cryobiopsy obtained a larger pleural tissue sample than forceps biopsy., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2019 Chung-Shu Lee et al.)

Background: Monocytes are the predominant innate immune cells at the early stage of Mycobacterium tuberculosis (M. tb) infection as the host defense against intracellular pathogens. Understanding the profile of different monocyte subpopulations and the dynamics of monocyte-related biomarkers may be useful for the diagnosis and prognosis of tuberculosis., Methods: We enrolled 129 individuals comprising patients with pulmonary tuberculosis (PTB) (n = 39), tuberculous pleurisy (TBP) (n = 28), malignant pleural effusion (MPE) (n = 21), latent tuberculosis infection (LTBI) (n = 20), and healthy controls (HC) (n = 21). Surface expression of CD14, CD16, and CD163 on monocytes was detected using flow cytometry. In addition, soluble CD163 (sCD163) was determined by enzyme linked immunosorbent assay., Results: Higher frequency of CD14 + CD16 + (15.7% vs 7.8%, P < 0.0001) and CD14 - CD16 + (5.3% vs 2.5%, P = 0.0011) monocytes and a decreased percentage of CD14 + CD16 - (51.0% vs 70.4%, P = 0.0110) cells was observed in PTB patients than in HCs. Moreover, PTB patients displayed a higher frequency of CD163 + cells in CD16 + monocytes than those in the HC group (40.4% vs 11.3%, P < 0.0001). The level of sCD163 was elevated in TBP patients and was higher in pleural effusion than in plasma (2116.0 ng/ml vs 1236.0 ng/ml, P < 0.0001). sCD163 levels in pleural effusion and plasma could be used to distinguish TBP from MPE patients (cut-off values: 1950.0 and 934.7 ng/ml, respectively; AUCs: 0.8418 and 0.8136, respectively). Importantly, plasma sCD163 levels in TBP patients decreased significantly after anti-TB treatment., Conclusions: Higher expression of membrane and soluble CD163 in active tuberculosis patients might provide insights regarding the pathogenesis of tuberculosis, and sCD163 may be a novel biomarker to distinguish TBP from MPE and to predict disease severity.

Background: In China, tuberculous pleural effusion is the most common cause for pleural effusion. Elevated ADH and positive tuberculin test usually are characteristic of tuberculous pleural effusion. We reported a 71-year-old male patient with elevated ADH and positive tuberculin test firstly misdiagnosed as tuberculous pleural effusion finally proven as pleural mesothelial sarcoma by thoracoscopic pathology., Methods: Appropriate laboratory tests and thoracentesis were carried out. Thoracoscopy and pathological biopsy were performed to differentiate tuberculous pleural effusion., Results: Chest CT showed right pleural effusion. ADH in pleural effusion was over 45 U/L and PPD test was positive. No abnormal cells were found in pleural effusion pathology. Pathology of thoracoscopic biopsy proved pleural mesothelioma., Conclusions: Elevated ADH and positive tuberculin test are not a specific index for tuberculosis and thoracoscopic biopsy pathology is crucial for differential diagnosis.

Liver abscesses, either pyogenic or amoebic, with or without the involvement of the pleura, are not infrequently encountered in children. Isolated tubercular liver abscess without active pulmonary, gastrointestinal or other clinical evidence of tuberculosis is, however, rare and more so its rupture into the pleura. We report a case of a 14-year-old girl who presented with a liver abscess rupturing into the pleura causing an empyema. Successful management was achieved by intercostal tube drainage and antitubercular treatment.

Objective: To assess the diagnostic value of video-assisted thoracoscopic surgery in exudative pleural effusions, and to evaluated the frequency of malignancy development with long term follow-up of patients defined as nonspecific pleuritis after surgery. ., Methods: The retrospective study was conducted at Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, Istanbul, Turkey, and comprised data of patients with undiagnosed exudative pleural effusions seen between January 2008 and December 2013. Data related to clinical, radiological, thoracoscopical, histopathological and follow-up periods were obtained from the hospital records. SPSS 15 was used for data analysis., Results: Of the 229 patients, 145(63.3%) were males and 84(36.7%) were females. The overall mean age was 54.5 }15.1 years. Malignancy was found in 84 (36.6%) patients, and tuberculosis in 26(11.4%). The remaining 119(52%) patients had nonspecific pleuritis and their mean follow-up period was 29.2}27.1 months (range: 1-103 months). Video-assisted thoracoscopic surgery was repeated in 3(2.52%) patients in the 1st, 4th and 16th months of followup period due to the recurrence of pleural effusion. Tuberculosis and mesothelioma were diagnosed in 1(0.8%) and 2(1.7%) cases, respectively., Conclusions: Video-assisted thoracoscopic surgery was found to be a valuable diagnostic procedure in patients with undiagnosed exudative pleural effusion.

Background: This study aimed to prospectively evaluate the efficacy and reliability of a diagnostic workup, triaging pleural biopsy method according to baseline computerized tomography (CT) findings in the diagnosis of pleural diseases., Methods: Patients with pleural pathology were divided into 3 arms according to findings on CT scan images. Arm A: patients with pleural thickening/lesion in addition to pleural effusion. These patients underwent CT scan-guided Abrams' needle pleural biopsy. Arm B: patients with pleural effusion alone or suspected benign asbestos pleurisy. This group underwent medical thoracoscopy (MT). Arm C: patients with only pleural thickening. This group underwent ultrasonography-guided cutting needle pleural biopsy. MT was planned in patients who did not have a specific diagnosis in the CT scan-guided Abrams' needle pleural biopsy group. When patients with a histopathologic diagnosis of fibrinous pleuritis after MT were assessed in terms of the risk factors for malignant pleural diseases, we offered a further invasive procedure., Results: A total of 164 patients were enrolled in the study. Diagnostic sensitivity after the initial procedure was 90.2% in Arm A, 93.3% in Arm B, 95.2% in Arm C, and 92.4% in the entire workup. The negative predictive value of the entire workup was 90.4% for malignant pleural mesothelioma, 97.1% for metastatic malignant pleural diseases, and 100% for tuberculous pleurisy. Five cases who had a diagnosis of fibrinous pleuritis after MT were detected to have risk factors, 4 of which (80%) indicated malignant disease. Complication rates were low and acceptable., Conclusion: Use of CT scans to triage an appropriate pleural biopsy method is associated with high diagnostic success. We recommend that the proposed diagnostic workup in this study may be used as a diagnostic algorithm for pleural diseases that require a histopathologic analysis. Determination of risk factors predicting malignant disease in patients where fibrinous pleuritis is reported after MT would be useful for clinical practice.

Currently, the diagnostic role of medical thoracoscopy in childhood pleural tuberculosis remains uncertain. Therefore, this retrospective study was conducted to evaluate the diagnostic performance of histological examination of tissue samples obtained by medical thoracoscopy in childhood pleural tuberculosis. Hospitalized children who underwent medical thoracoscopy between May 2012 and March 2016 were included in the study. Tissue samples obtained by thoracoscopy were submitted for histological examination (hematoxylin and eosin staining). Descriptive statistical methods were used for data interpretation, and the data were expressed as the mean ± standard deviation. The childhood tuberculosis patients had the following characteristics: 11 had pleural tuberculosis and 9 had pleural tuberculosis + pulmonary tuberculosis, the average age was 13.0 ± 2.2 years old, 60% were male, 26.3% (5/19) of patients tested positive for acid-fast bacilli positive in smears, 21.1% (4/19) of patients were positive for TB-PCR, and 90% (18) of pleural tuberculosis patients were positive in the culture for Mycobacterium tuberculosis. The sensitivity of histological examinations of tissue samples obtained by thoracoscopy in the detection of pleural tuberculosis was 80% (16/20). Complications were reported in 15 cases, and all complications disappeared spontaneously without any specific treatment. Therefore, we concluded that medical thoracoscopy was a sensitive and safe tool for the detection of childhood pleural tuberculosis.

Extrapulmonary tuberculosis in children tends to be more severe than the adults. It can affect almost any organ system of the body. The clinical manifestations are often non-specific. Imaging findings are also not always very specific. This article describes the imaging spectrum of pediatric extrapulmonary tuberculosis.

Chest is the commonest site of involvement by tuberculosis (TB) in children; lungs being the most frequently affected region, followed by nodes, pleura and chest wall. It is difficult to diagnose TB in children due to lack of overt symptoms and difficulty in obtaining samples for microbiological confirmation. Hence various imaging modalities play an important role in diagnostic algorithm as well as in follow-up after treatment. Standardization of chest radiograph reporting in context of clinically suspected TB is the need of the hour so as to suggest a proper diagnosis and avoid over-diagnosis. This article aims to discuss the imaging features of chest tuberculosis according to the site of involvement on various imaging modalities in the pediatric population.

Objective: Pleural fluid adenosine deaminase (ADA) is a useful diagnostic test for tuberculous pleural effusion (TPE), but its exact threshold and accuracy in clinical decision-making is unclear. We aimed to assess diagnostic performance of ADA in TPE and to clarify its optimal diagnostic threshold., Methods: We searched PubMed, Embase, and Cochrane Library databases for articles indexed up to October 2018. We included English language studies that provided both sensitivity and specificity of ADA in TPE diagnosis. Summary estimates for sensitivity and specificity were obtained through bivariate random effects model, both overall and at prespecified threshold ranges of <36, 40±4, 45-65 and >65 IU/L., Results: We retrieved 2162 citations, and included 174 publications with 27009 patients. All studies showed high risk of bias. Summary sensitivity, specificity and diagnostic odds ratio estimates were 0.92 (95% CI 0.90-0.93), 0.90 (95% CI 0.88-0.91) and 97.42 (95% CI 74.90-126.72) respectively. 65 studies with ADA threshold of 40±4 IU/L showed summary sensitivity and specificity of 0.93 (95% CI 0.90-0.95) and 0.90 (95% CI 0.87-0.91) respectively. Four studies with ADA threshold >65 IU/L showed summary sensitivity and specificity of 0.86 (95% CI 0.61-0.96) and 0.94 (95% CI 0.80-0.99) respectively., Conclusion: ADA levels in pleural fluid show good diagnostic accuracy in diagnosis of TPE; however, all included studies showed high risk of bias. It was not possible to derive any firm inference on relative clinical utility of different diagnostic thresholds., Competing Interests: The authors have declared that no competing interests exist.

Tuberculosis pleural effusion (TPE) and parasitic pleural effusion (PPE) present with similar clinical manifestations. We evaluated the pleural fluid features of TPE and PPE.A total of 76 patients with pleuritis, including 25 patients with TPE and 51 patients with PPE were retrospectively studied. Pleural fluid was sent for analyses of protein, cytology, cell count, acid fast bacilli (AFB) staining, Gram stain, culture, sensitivity, and adenosine dehydrogenase (ADA).The proportion of eosinophilia present in the PPE group was significantly higher than that in the TPE group (P < .001). However, the proportion of lymphocytes found in the TPE group was significantly higher than that in the PPE group (P < .001). The mean level (SD) of ADA was 46.99 ± 22.09 U/L in the TPE group and 39.08 ± 23.03 U/L in the PPE group. No difference was detected between the study groups in terms of the ADA level of the pleural fluid (P > .05).When the results of pleural fluid testing reveal marked eosinophilia and a low proportion of lymphocytes, physicians should consider a diagnosis of PPE, especially for patients who live in or have traveled to endemic areas.

Thoracoscopy in the endoscopy suite, has a high diagnostic yield of undiagnosed pleural effusions with minimal and mild complications. Whereas relatively minimal invasive techniques, such as thoracentesis, image-guided pleural biopsy or blind pleural biopsy, can yield sufficient cell or tissue material to establish the diagnosis of the underlying condition, more definite invasive diagnostic and therapeutic procedure, such as thoracoscopy, may be required for accurate sampling and diagnosis, and further provide real-time treatment options in same procedure. If thoracoscopy is considered the gold standard for the diagnosis is a fact in case. The current review aims to provide informations on thoracoscopy indications in benign pleural diseases according to up to date publications., (© 2018 John Wiley & Sons Ltd.)

Background: There is no randomized study comparing pleural cryobiopsy (CB) and flexible forceps biopsy (FFB) in subjects undergoing medical thoracoscopy for the diagnosis of pleural effusions., Objective: In this crossover study, we compared the diagnostic yield of CB versus FFB in subjects undergoing semirigid thoracoscopy., Methods: Subjects undergoing semirigid thoracoscopy for undiagnosed pleural effusions were subjected to both CB and FFB, with the order of performing the biopsy randomized in a 1:1 ratio. The primary outcome was the diagnostic yield obtained with CB versus FFB. The secondary outcomes included the biopsy size, depth, histologic interpretability, artefacts, the difficulty of performing biopsy on an operator-rated visual analog scale, the severity of bleeding observed at the time of the biopsy, and the duration of the procedure., Results: Of the 201 subjects screened, 50 (mean age 52.4 years; 18 women) were included. The diagnostic yield of CB (78.0%) was not different from FFB (76.0%, p = 1.00). CB yielded a larger specimen than FFB (median size 7.0 vs. 4.0 mm; p < 0.001), and a greater depth of specimens (up to the pleural fat or deeper, CB vs. FFB 65.2 vs. 40.8%; p = 0.02). The CB procedure was quicker than FFB (median duration 10 vs. 15 min; p < 0.001). There were no significant differences in the difficulty of performing the biopsy, the severity of bleeding, histologic interpretability, or artefacts in the specimens between the CB and FFB groups., Conclusion: The diagnostic yield of pleural CB was comparable to FFB during semirigid thoracoscopy., (© 2019 S. Karger AG, Basel.)

BACKGROUND Traditional diagnostic methods for tuberculosis (TB) cannot be reliably applied to tuberculous pleurisy. Therefore, this prospective, randomized, controlled trial was performed to compare the diagnostic sensitivity and safety of ultrasound-guided cutting-needle pleural biopsy versus thoracoscopic pleural biopsy in patients suspected of tuberculous pleurisy following inconclusive thoracentesis. MATERIAL AND METHODS A total of 196 adult patients with acid-fast bacillus (AFB)-negative exudative pleural effusions clinically suspected of tuberculous pleurisy were recruited. Enrollees were randomized into 2 cohorts: ultrasound-guided cutting-needle pleural biopsy (n=96) or thoracoscopic pleural biopsy (n=96). The overall diagnostic yields, diagnostic sensitivities for tuberculous pleurisy, and post-procedural complications for both cohorts were statistically compared. RESULTS Ultrasound-guided pleural biopsy displayed an overall diagnostic yield of 83%, while thorascopic pleural biopsy displayed a similar overall diagnostic yield of 86% (χ²=1.88, df=1, p=0.17). There were 127 patients conclusively diagnosed with tuberculous pleurisy, resulting in a tuberculous pleurisy prevalence of 65% in this patient population (66% in the ultrasound cohort vs. 63% in the thoracoscopy cohort; p>0.05). Ultrasound-guided pleural biopsy displayed a sensitivity of 82% in detecting tuberculous pleurisy, while thorascopic pleural biopsy displayed a similar sensitivity of 90% (χ²=1.05, df=1, p=0.30). The sensitivities of these 2 modalities did not significantly differ based on the degree of pleural thickening (p>0.05). Post-procedural complications were minor. CONCLUSIONS Ultrasound-guided and thoracoscopic pleural biopsy both display strong (>80%) but statistically similar overall diagnostic yields for diagnosing pleural effusions following inconclusive thoracentesis. Both modalities also display strong (>80%) but statistically similar sensitivities in detecting tuberculous pleurisy.

The sensitivity and specificity of exfoliative cell cytology for the diagnosis of exudative pleural effusions varies widely according to the etiologic causes. The aim of this study is to assess the diagnostic value of exfoliative cell cytology for the identification of exudative pleural effusions. This is a retrospective study of the patients with an exudative pleural effusion admitted at our clinic in the last twenty years. We have conducted the clinical, the cytological findings, and the diagnostic results of six hundred patients from hospital records.  Male to female ratio was 2.2:1 with a mean age of 42.8 years (range 18-78 years) among the patients. Samples were processed and evaluated according to the standard methods. Cytology results were reviewed and the patients were stratified according to the final diagnosis of their disease. Of the six hundred exudative effusions, 240 were malignant on exfoliative cytology pleural fluid alone. Adenocarcinoma was the most common type of malignancy. Tuberculosis was the second most frequent etiology for the exudative effusions followed by infection and collagen vascular diseases. Diagnostic accuracy of cytology showed a good correlation with the final diagnosis with an overall 70.1% sensitivity, 62.5% specificity, and a 95.9% positive predictive value for all exudative pleural effusions. Cytologic examination of the pleural fluid is a simple non-invasive procedure as the initial step for the diagnostic work up of patients with a pleural effusion.  Exfoliative cytology provides high a final diagnostic yield for the identification of an exudative pleural effusion etiology. Furthermore, cytologic analysis leads the clinician into the correct diagnostic pathway as the most informative laboratory tool even when it was not diagnostic by itself for equivocal cases.

Background: Pleural tuberculosis (PlTB) is the most common extrapulmonary manifestation of this infectious disease which still presents high mortality rates worldwide. Conventional diagnostic tests for PlTB register multiple limitations, including the lack of sensitivity of microbiological methods on pleural specimens and the need of invasive procedures such as pleural biopsy performance. In this scenario, the search for biological markers on pleural fluid (PF) has been the target of several studies as a strategy to overcome the limitations of PlTB diagnosis. This study aims to evaluate the use either isolated or in combination with adenosine deaminase (ADA), interferon-gamma (IFN-γ), interferon-gamma inducible protein of 10-kD (IP-10) levels on PF in order to guide an accurate anti-TB treatment in microbiologically non-confirmed cases., Methods and Findings: Eighty patients presenting pleural effusion under investigation were enrolled in a cross-sectional study conducted at Pedro Ernesto University Hospital, Rio de Janeiro, RJ, Brazil. Peripheral blood (PB) and PF samples collected from all patients were applied to the commercial IFN-γ release assay, QuantiFERON-TB Gold In-Tube, and samples were analyzed for IFN-γ and IP-10 by immunoassays. ADA activity was determined on PF by the colorimetric method. Based on microbiological and histological criteria, patients were categorized as follow: confirmed PlTB (n = 16), non-confirmed PlTB (n = 17) and non-PlTB (n = 47). The Mycobacterium tuberculosis antigen-specific production of IFN-γ and IP-10 on PB or PF did not show significant differences. However, the basal levels of these biomarkers, as well as the ADA activity on PF, were significantly increased in confirmed PlTB in comparison to non-PlTB group. Receiver operating characteristics curves were performed and the best cut-off points of these three biomarkers were estimated. Their either isolated or combined performances (sensitivity [Se], specificity [Sp], positive predictive value [PPV], negative predictive value [NPV] and accuracy [Acc]) were determined and applied to Venn's diagrams among the groups. Based on the confirmed PlTB cases, IFN-γ showed the best performance of them at a cut-off point of 2.33 IU/mL (Se = 93.8% and Sp = 97.9%) followed by ADA at a cut-off of 25.80 IU/L (Se = 100% and Sp = 84.8%) and IP-10 (Cut-point = 4,361.90 pg/mL, Se = 75% and Sp = 82.6%). IFN-γ plus ADA (cut-point: 25.80 IU/L) represent the most accurate biomarker combination (98.4%), showing Se = 93.7%, Sp = 100%, PPV = 100% and NPV = 97.9%. When this analysis was applied in non-confirmed PlTB, 15/17 (88.2%) presented at least two positive biomarkers in combination., Conclusion: IFN-γ, IP-10, and ADA in PlTB effusions are significantly higher than in non-PlTB cases. IFN-γ is an excellent rule-in and rule-out test compared to IP-10 and ADA. The combination of IFN-γ and ADA, in a reviewed cut-off point, showed to be particularly useful to clinicians as their positive results combined prompts immediate treatment for TB while both negative results suggest further investigation., Competing Interests: The authors have declared that no competing interests exist.

Background and Objective: Extrapulmonary tuberculosis (EPTB) accounts for ~15% of all TB patients, and TB pleural effusion is the second most common site of EPTB. The diagnosis of pleural TB is challenging due to the pauci-bacillary nature of the disease. Histopathology of thoracoscopically obtained pleural biopsy provides the highest diagnostic yield. The Xpert MTB/RIF assay (Xpert) is a PCR test that can identify both Mycobacterium tuberculosis (MTB) and rifampicin resistance. Currently, there is a lack of clarity regarding the value of Xpert on pleural tissue. We report our experience of using Xpert on thoracoscopic pleural biopsy samples., Methods: We retrospectively reviewed the records of patients who underwent thoracoscopy in our institution over a 1-year period. Relevant clinical details; indications; and results of tests on pleural tissue and fluid, including histopathology, mycobacterial cultures and Xpert, were extracted., Results: Of the 156 patients who underwent thoracoscopy, 73 (47%) had TB, 66 (42%) malignancy and 17 (11%) other conditions. Histopathology was diagnostic in all the 73 TB patients (100%). The yields of the microbiological tests against histopathology on thoracoscopic biopsy sample and pleural fluid were: pleural tissue Xpert 45%, pleural tissue culture 39%, pleural fluid culture 17% and pleural fluid Xpert 14%. Pleural tissue provided higher yields than fluid in both Xpert and culture (P < 0.05). Pleural tissue Xpert provided a higher yield than culture and substantially improved yield compared with closed pleural biopsy as we previously reported., Conclusion: Thoracoscopic pleural biopsy results in increased sensitivity on Xpert testing., (© 2018 Asian Pacific Society of Respirology.)

Tuberculosis (TB) is the leading infectious cause of death worldwide, and the commonest cause of death in people living with HIV. Globally, pleural TB remains one of the most frequent causes of pleural exudates, particularly in TB-endemic areas and in the HIV positive population. Most TB pleural effusions are exudates with high adenosine deaminase (ADA), lymphocyte-rich, straw-coloured and free flowing, with a low yield on mycobacterial culture. TB pleurisy can also present as loculated neutrophil-predominant effusions which mimic parapneumonic effusions. Rarely, they can present as frank TB empyema, containing an abundance of mycobacteria. Up to 80% of patients have parenchymal involvement on chest imaging. The diagnosis is simple if M. tuberculosis is detected in sputum, pleural fluid or biopsy specimens, and the recent advent of liquid medium culture techniques has increased the microbiological yield dramatically. Where the prevalence of TB is high the presence of a lymphocyte-predominant exudate with a high ADA has a positive predictive value of 98%. In low prevalence areas, the absence of an elevated ADA and lymphocyte predominance makes TB very unlikely, and pleural biopsy should be performed to confirm the diagnosis. Pleural biopsy for liquid culture and susceptibility testing must also be considered where the prevalence of drug resistant TB is high. Treatment regimens are identical to those administered for pulmonary TB. Initial pleural drainage may have a role in symptom relief and in hastening the resolution of the effusion. Surgical intervention may be required in loculated effusions and empyemas., (© 2018 John Wiley & Sons Ltd.)

The ability of Mycobacterium tuberculosis (Mtb) to persist in its human host relies on numerous immune evasion strategies, such as the deregulation of the lipid metabolism leading to the formation of foamy macrophages (FM). Yet, the specific host factors leading to the foamy phenotype of Mtb-infected macrophages remain unknown. Herein, we aimed to address whether host cytokines contribute to FM formation in the context of Mtb infection. Our approach is based on the use of an acellular fraction of tuberculous pleural effusions (TB-PE) as a physiological source of local factors released during Mtb infection. We found that TB-PE induced FM differentiation as observed by the increase in lipid bodies, intracellular cholesterol, and expression of the scavenger receptor CD36, as well as the enzyme acyl CoA:cholesterol acyl transferase (ACAT). Importantly, interleukin-10 (IL-10) depletion from TB-PE prevented the augmentation of all these parameters. Moreover, we observed a positive correlation between the levels of IL-10 and the number of lipid-laden CD14 + cells among the pleural cells in TB patients, demonstrating that FM differentiation occurs within the pleural environment. Downstream of IL-10 signaling, we noticed that the transcription factor signal transducer and activator of transcription 3 was activated by TB-PE, and its chemical inhibition prevented the accumulation of lipid bodies and ACAT expression in macrophages. In terms of the host immune response, TB-PE-treated macrophages displayed immunosuppressive properties and bore higher bacillary loads. Finally, we confirmed our results using bone marrow-derived macrophage from IL-10 -/- mice demonstrating that IL-10 deficiency partially prevented foamy phenotype induction after Mtb lipids exposure. In conclusion, our results evidence a role of IL-10 in promoting the differentiation of FM in the context of Mtb infection, contributing to our understanding of how alterations of the host metabolic factors may favor pathogen persistence.

Human Leukocyte Antigen-G (HLA-G), a non-classical, class Ib molecule, has been shown to mediate immunoregulatory functions by inducing apoptosis, inhibits cytotoxicity and differentiation by modulating cytokine secretion. Due to its immune-suppressive function, it facilitates tolerance in feto-maternal interface and transplantation. In contrary, it favours immune evasion of microbes and tumors by inhibiting immune and inflammatory responses. In Tuberculosis (TB), we previously reported differential expression of HLA-G and its receptor Ig-like transcript -2 (ILT-2) in disseminated vs. localized Tuberculosis. The present study explores the impact of HLA-G inhibition on the function of T cells and monocytes, in TB Pleural Effusion (PE), a localized form of TB. Blocking of HLA-G resulted in significant increase in IFN-γ and TNF-α production by CD3 + T cells. Additionally, we observed that HLA-G influences the apoptosis and cytotoxic effect of T cells from TB- PE patients. Next, we checked the impact of interaction between HLA-G and ILT-4 receptor in monocytes derived from TB-PE patients upon blocking and observed significant increase in IFN-γ production. The present study reveals for the first time HLA-G mediated suppression of Th1 cytokines, especially, IFN-γ and TNF-α in TB-PE patients., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

A 44-year-old woman was referred to our hospital with pleural effusion and unknown fever. Mycobacterium tuberculosis was not detected by culture of pleural effusion and sputum and gastric fluid. Pleural fluid was serous and exudative, and cytological examination showed no malignant cells. Computed tomography revealed a little pleural thickening of the right middle lobe and massive pleural effusion. As acute pleurisy was suspected based on the findings of imaging studies, thoracoscopy was performed under general anesthesia. Many yellowish-white, small nodules were seen on the parietal pleura, and white small nodule were seen on the visceral pleura of the right middle lobe. Mycobacterium tuberculosis was not detected by culture and polymerase chain reaction for Mycobacterium tuberculosis( TB-PCR) of parietal pleura and pleural effusion, but was detected by only culture and TB-PCR of visceral pleura, yielding a diagnosis of tuberculous pleurisy. Her symptoms improved and the right pleural effusion decreased with isoniazid (INH), rifampicin (RFP), ethambutol (EB) and pyrazinamide(PZA) treatment.

Although the majority of patients with Mycobacterium tuberculosis have pulmonary involvement, some cases have pleural involvement as extra-pulmonary sites of infection. We herein report a case of upper lobe-predominant pulmonary fibrosis that developed in a 47-year-old male with a history of bilateral tuberculous pleurisy. Based on his chest radiological findings, pleuroparenchymal fibroelastosis (PPFE) was most strongly suspected, and a surgical lung biopsy (SLB) was performed to obtain a pathological diagnosis. The SLB specimens showed interstitial pneumonia with pleural involvement without any characteristic findings of PPFE. Careful discretion in obtaining a precise diagnosis of this condition should be practiced in such cases.

The use of biomarkers on pleural fluid (PF) specimens may assist the decision-making process and enhance clinical diagnostic pathways. Three paradigmatic examples are heart failure, tuberculosis and, particularly, malignancy. An elevated PF concentration of the amino-terminal fragment of probrain natriuretic peptide (>1500 pg/ml) is a hallmark of acute decompensated heart failure. Adenosine deaminase, interferon-γ and interleukin-27 are three valuable biomarkers for diagnosing tuberculous pleurisy, yet only the first has been firmly established in clinical practice. Diagnostic PF biomarkers for malignancy can be classified as soluble-protein based, immunocytochemical and nucleic-acid based. Soluble markers (e.g. carcinoembryonic antigen (CEA), carbohydrate antigen 15-3, mesothelin) are only indicative of cancer, but not confirmatory. Immunocytochemical studies on PF cell blocks allow: (a) to distinguish mesothelioma from reactive mesothelial proliferations (e.g. loss of BAP1 nuclear expression, complemented by the demonstration of p16 deletion using fluorescence in situ hybridization, indicate mesothelioma); (b) to separate mesothelioma from adenocarcinoma (e.g. calretinin, CK 5/6, WT-1 and D2-40 are markers of mesothelioma, whereas CEA, EPCAM, TTF-1, napsin A, and claudin 4 are markers of carcinoma); and (c) to reveal tumor origin in pleural metastases of an unknown primary site (e.g. TTF-1 and napsin A for lung adenocarcinoma, p40 for squamous lung cancer, GATA3 and mammaglobin for breast cancer, or synaptophysin and chromogranin A for neuroendocrine tumors). Finally, PF may provide an adequate sample for analysis of molecular markers to guide patients with non-small cell lung cancer to appropriate targeted therapies. Molecular testing must include, at least, mutations of epidermal growth-factor receptor and BRAF V600E, translocations of rat osteosarcoma and anaplastic lymphoma kinase, and expression of programmed death ligand 1.

Pleural macrophages play critical roles in pathogenesis of tuberculous pleuritis, but very little is known about their response to anti-tuberculosis antibiotics treatment. Here, we examined whether and how pleural macrophages change in phenotype, transcription and function following antibiotics treatment in patients with tuberculous pleuritis. Results show pro-inflammatory cytokines were down-regulated significantly post antibiotic treatment in the pleural effusions and pleural macrophages up-regulated markers characteristic of M2 macrophages such as CD163 and CD206. Differential expression analysis of transcriptomes from four paired samples before and after treatment identified 230 treatment-specific responsive genes in pleural macrophages. Functional analysis identified interferon-related pathway to be the most responsive genes and further confirmed macrophage polarization to M2-like phenotype. We further demonstrate that expression of a significant fraction of responsive genes was modulated directly by antibiotics in pleural macrophages in vitro. Our results conclude that pleural macrophages polarize from M1-like to M2-like phenotype within a mean of 3.5 days post antibiotics treatment, which is dependent on both pleural cytokine environment and direct modulatory effects of antibiotics. The treatment-specific genes could be used to study the roles of pleural macrophages in the pathogenesis of tuberculous pleuritis and to monitor the response to antibiotics treatment.