OBJECTIVE: To evaluate the efficacy of urokinase (UK) treatment for tuberculous pleural effusion (TPE).
METHODS: We searched Chinese biomedical literature database, WanFang data, CNKI, PubMed, EMbase, Web of Science and The Cochrane Library for the randomized controlled trials (RCTs) of urokinase treatment for tuberculous pleurisy from January 2000 to February 2023. Pleural tuberculosis, urokinase and randomized controlled trial were used as keywords. The eligible studies were meta-analyzed by using Revman 5.4.1: risk of bias was assessed, mean difference (MD) and 95% CI were used for continuous variables, pooled studies were conducted using random-effects or fixed-effects models, forest plots were drawn to analyze efficacy, and funnel plots were drawn to discuss publication bias.
RESULTS: Twenty-nine RCTs were included. The meta-analyzed results showed that, on the basis of routine anti-tuberculosis, comparison between the treatment group treated with urokinase and the control group treated with antituberculosis alone, the time of pleural effusion absorption [MD-5.82, 95%CI (- 7.77, - 3.87); P<0.00001] and the residual pleural thickness [MD-1.31, 95%CI (- 1.70, - 0.91); P<0.00001], pleural effusion drainage volume [MD 822.81, 95%CI (666.46,977.96); P<0.00001], FVC%pred [MD 7.95, 95%CI (4.51,11.40); P<0.00001], FEV1%pred [MD 12.67, 95%CI (10.09,15.24); P<0.00001] were significantly different.
CONCLUSIONS: The clinical effect of urokinase is better than that of antituberculous therapy alone: it can increase total pleural effusion, decrease residual pleural thickness, improve the pulmonary function, and shorten the time of pleural effusion absorption.

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 IS1081 in DNA were quantified using dPCR. The overall area under the curve of IS6110-dPCR was greater than that of IS1081-dPCR (0.85 versus 0.79). PF IS6110 OR IS1081-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 IS6110 OR IS1081-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 IS6110 OR IS1081-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 IS6110 OR IS1081-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 IS6110 OR IS1081-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.

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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.

Background: Pleural loculation in childhood pleural tuberculosis (TB) remains a problem in practice, it is usually associated with failure drainage. Therefore, to improve the management of childhood pleural TB, a retrospective study was conducted to identify the risk factors associated with loculated effusion in childhood pleural TB. Methods: Between January 2006 and December 2019, consecutive children (≤15 years old) with tuberculous pleural effusion (definite and possible) were included for further analysis. The demographic, clinical, laboratory, and radiographic features were collected from the medical records. Univariate and multivariate logistic regressions were used to explore the factors associated with the presence of pleural loculation in children with pleural TB. Results: A total of 154 children with pleural TB (definite, 123 cases; possible, 31 cases) were included in our study and then were classified as loculated effusion (n = 27) and non-loculated effusion (n = 127) groups by chest X-ray or ultrasonography. Multivariate analysis revealed that male gender (age-adjusted OR = 3.903, 95% CI: 1.201, 12.683), empyema (age-adjusted OR = 4.499, 95% CI: 1.597, 12.673), peripheral monocytes ≤0.46 × 109/L (age-adjusted OR = 4.122, 95% CI: 1.518, 11.193) were associated with the presence of loculated effusion in children with pleural TB. Conclusion: In conclusion, several characteristics, such as male gender, empyema, and peripheral monocyte count have been identified as risk factors for pleural loculation in children with pleural TB. Our findings may be helpful to improve the management of pleural loculation in childhood pleural TB.

Background: Until now, the factor of tuberculous empyema (TE) in children with pleural tuberculosis (TB) remains unclear. Therefore, a retrospective study was conducted to assess the factors associated with the presence of TE in children. Methods: Between January 2006 and December 2019, consecutive children patients (≤ 15 years old) with suspected pleural TB were selected for further analysis. Empyema was defined as grossly purulent pleural fluid. The demographic, clinical, laboratory, and radiographic features were collected from the electrical medical records retrospectively. Univariate and multivariate logistic regressions were used to explore the factors associated with the presence of TE in children with pleural TB. Results: A total of 154 children with pleural TB (definite, 123 cases; possible, 31 cases) were included in our study and then were classified as TE (n = 27) and Non-TE (n = 127) groups. Multivariate analysis revealed that surgical treatment (age- and sex-adjusted OR = 92.0, 95% CI: 11.7, 721.3), cavity (age- and sex-adjusted OR = 39.2, 95% CI: 3.2, 476.3), pleural LDH (>941 U/L, age- and sex-adjusted OR = 14.8, 95% CI: 2.4, 90.4), and temperature (>37.2°C, age- and sex-adjusted OR = 0.08, 95% CI: 0.01, 0.53) were associated with the presence of TE in children with pleural TB. Conclusion: Early detection of the presence of TE in children remains a challenge and several characteristics, such as surgical treatment, lung cavitation, high pleural LDH level, and low temperature, were identified as factors of the presence of TE in children with pleural TB. These findings may improve the management of childhood TE.

BACKGROUND: A 3-year prospective study was conducted to evaluate the efficacy of Xpert MTB/RIF (Xpert) in the diagnosis of pleural tuberculosis (pTB) on contrast -enhanced ultrasound (CEUS)-guided pleural biopsy specimens.
METHODS: Patients suspected with pTB were prospectively enrolled to receive CEUS-guided biopsy. Specimens (pleural tissue and fluid) were submitted for Xpert and other routine examinations. Surgical thoracoscopy was performed on undiagnosed cases.
RESULTS: A total of 316 patients were enrolled, including 280 cases of pTB (definite 195, possible 85) and 36 cases of non-pTB. The sensitivity of Xpert was 69.64% (195/280) in biopsy specimens, which was significantly higher than that in pleural effusion specimens (p < 0.01). In 195 definite cases, the highest sensitivity of 100% (195/195) and NPV of 29.75% (36/121) were achieved by Xpert on biopsy specimens. Xpert-positive results were obtained in 149 culture-negative cases and 90 histopathological MTB PCR-negative cases. The incidence of necrosis by CEUS in Xpert-positive pTB was significantly higher than that in Xpert-negative pTB (χ2 = 72.41; p < 0.01). No serious complications occurred.
CONCLUSIONS: Xpert achieved highly diagnostic sensitivity in pTB through CEUS-guided biopsy sampling, especially on necrotic lesions, which was proven to be efficient, minimally invasive and safe.

BACKGROUND: Pleural effusion (PE) Xpert has limited use in the diagnosis of pleural tuberculosis (TB). However, the diagnostic incremental value of sputum Xpert for pleural TB diagnosis remains unclear.
METHODS: Between March 2018 and October 2019, patients with certain causes (such as TB, malignancy, and pneumonia) of PE were enrolled in our study. Sputum and PE were collected from all patients and sent for acid-fast bacilli smear (Auramine O staining), mycobacterial culture (Lowenstein-Jensen media), and Xpert. The differences in the sensitivities of these TB assays between different groups were examined with the chi-square test.
RESULTS: One hundred and twenty-seven PE patients were enrolled in the study and then were divided into pleural TB (n = 104) and other causes of PE (excluding TB, referred as non-pleural TB; n = 23). Compared with PE Xpert (11.5%, 12/104), sputum Xpert has a higher sensitivity of 25.0% (26/104, p = .012 < .05). The combination of sputum and PE has a non-significant higher sensitivity of 31.7% (33/104) than Xpert on sputum (p > .05). Culture using both sputum and PE combined has a high sensitivity of 43.3% (45/104).
CONCLUSIONS: Compared to PE Xpert, sputum Xpert showed an incremental diagnostic yield in the diagnosis of pleural TB and is expected to speed up the diagnosis of pleural TB.

BACKGROUND: Delay in diagnosis and treatment worsens the disease and clinical outcomes, which further enhances the transmission of tuberculosis (TB) in the community. Therefore, this study aims to assess treatment delay and its associated factors among childhood pleural TB patients in China.
METHODS: Between January 2006 and December 2019, consecutive patients aged ≤15 years with definite or possible pleural TB were included for analysis. Treatment delay duration was defined as the time interval from the onset of symptoms to treatment initiation and was stratified into two categories: < 30 days, ≥30 days (median delay day is 30 days). The electronic medical records of children were reviewed to obtain demographic characteristics, clinical characteristics, laboratory examinations, and radiographic findings. Univariate and multivariate logistic regressions were used to explore the factors associated with treatment delay in patients.
RESULTS: A total of 154 children with pleural TB were included, with a mean age of 12.4 ± 3.3 years. The median treatment delay was 30 days (interquartile range, 10-60 days) and 51.3% (n = 79) of patients underwent a treatment delay. Multivariate analysis revealed that heart rate (≤92 beats/min, age-adjusted OR = 2.503, 95% CI: 1.215, 5.155) and coefficient of variation of red cell distribution width (RDW-CV, ≥12.9%, age-adjusted OR = 4.705, 95% CI: 2.048, 10.811) were significant risk factors for treatment delays in childhood pleural TB.
CONCLUSIONS: Our findings suggested that a significant treatment delay occurs among children with pleural TB in China. Patients with a low heart rate or a high RDW-CV experienced delays in the initiation of anti-TB therapy. Therefore, well awareness of the associations between clinical characteristics and treatment delay may improve the management of children with pleural TB and enable us to develop preventive strategies to reduce the treatment delay.

To investigate the effects of the surface markers B- and T-lymphocyte attenuator (BTLA) and B7 homologous body 4 (B7-H4) on expression of CD83, and Human Leukocyte Antigen-DR isotype (HLA-DR) that can activate dendritic cells (DCs). Flow cytometry was used to detect the co-expression of BTLA and B7-H4 on myeloid DCs (mDCs) in peripheral blood (PB) and pleural effusions (PE) in 15 volunteers and 20 tuberculous pleurisy (TP) patients. Co-expression of BTLA and B7-H4 (double positive (DP)) mDCs in PB and PE of TP patients were enhanced. The proportion of DP mDC in PB decreased markedly after 2 weeks treatment, but was still greater than in controls. Expression of CD83 and HLA-DR on DP mDCs was higher than on BTLA and B7-H4 double negative (DN) expressing mDCs in PB of different TP groups. Expression of CD83 on DP mDCs in PB and PE of TP patients was greater than that of controls. Expression of HLA-DR on DP mDCs in TP patient PB was lower than in TP PE and controls. In pleural tuberculosis (TB) patients, high expression of BTLA and B7-H4 promoted a high level of CD83 and HLA-DR, which had a negative regulatory effect on mDCs on anti-TB immunity.