Accuracy of cell-free Mycobacterium tuberculosis DNA testing in pleural effusion for diagnosing tuberculous pleurisy: a multicenter cross-sectional study.

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

The evolving landscape of IL-10, IL-22 and IL-26 in pleurisy especially in tuberculous pleurisy.

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

The levels of soluble CD137 are increased in tuberculosis patients and associated with disease severity and prognosis.

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

Performance of CBNAAT on Pleural Biopsies Obtained by Semirigid Thoracoscopy for Diagnosis of Unexplained Pleural Effusion: A Prospective Study from North India.

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

Myeloid-derived suppressor cells in pleural effusion as a diagnostic marker for early discrimination of pulmonary tuberculosis from pneumonia.

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

Clinical significance of pleural fluid lactate dehydrogenase/adenosine deaminase ratio in the diagnosis of tuberculous pleural effusion.

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

Enhanced differential evolution algorithm for feature selection in tuberculous pleural effusion clinical characteristics analysis.

Tuberculous pleural effusion poses a significant threat to human health due to its potential for severe disease and mortality. Without timely treatment, it may lead to fatal consequences. Therefore, early identification and prompt treatment are crucial for preventing problems such as chronic lung disease, respiratory failure, and death. This study proposes an enhanced differential evolution algorithm based on colony predation and dispersed foraging strategies. A series of experiments conducted on the IEEE CEC 2017 competition dataset validated the global optimization capability of the method. Additionally, a binary version of the algorithm is introduced to assess the algorithm's ability to address feature selection problems. Comprehensive comparisons of the effectiveness of the proposed algorithm with 8 similar algorithms were conducted using public datasets with feature sizes ranging from 10 to 10,000. Experimental results demonstrate that the proposed method is an effective feature selection approach. Furthermore, a predictive model for tuberculous pleural effusion is established by integrating the proposed algorithm with support vector machines. The performance of the proposed model is validated using clinical records collected from 140 tuberculous pleural effusion patients, totaling 10,780 instances. Experimental results indicate that the proposed model can identify key correlated indicators such as pleural effusion adenosine deaminase, temperature, white blood cell count, and pleural effusion color, aiding in the clinical feature analysis of tuberculous pleural effusion and providing early warning for its treatment and prediction.

Diagnostic accuracy and cellular origin of pleural fluid CXCR3 ligands for tuberculous pleural effusion.

BACKGROUND: Pleural biomarkers represent potential diagnostic tools for tuberculous pleural effusion (TPE) due to their advantages of low cost, short turnaround time, and less invasiveness. This study evaluated the diagnostic accuracy of two CXCR3 ligands, C-X-C motif chemokine ligand 9 (CXCL9) and CXCL11, for TPE. In addition, we investigated the cellular origins and biological roles of CXCL9 and CXCL11 in the development of TPE. METHODS: This double-blind study prospectively enrolled patients with undiagnosed pleural effusion from two centers (Hohhot and Changshu) in China. Pleural fluid on admission was obtained and levels of CXCL9 and CXCL11 were measured by an enzyme-linked immunosorbent assay (ELISA). The receiver operating characteristic (ROC) curve and the decision curve analysis (DCA) were used to evaluate their diagnostic accuracy and net benefit, respectively. THP-1 cell-derived macrophages were treated with Bacillus Calmette-Guérin (BCG), and quantitative real-time PCR (qRT-PCR) and ELISA were used to determine the mRNA and protein levels of CXCL9 and CXCL11. The chemoattractant activities of CXCL9 and CXCL11 for T helper (Th) cells were analyzed by a transwell assay. RESULTS: One hundred and fifty-three (20 TPEs and 133 non-TPEs) patients were enrolled in the Hohhot Center, and 58 (13 TPEs and 45 non-TPEs) were enrolled in the Changshu Center. In both centers, we observed increased CXCL9 and CXCL11 in TPE patients. The areas under the ROC curves (AUCs) of pleural CXCL9 and CXCL11 in the Hohhot Center were 0.70 (95 % CI: 0.55-0.85) and 0.68 (95 % CI: 0.52-0.84), respectively. In the Changshu Center, the AUCs of CXCL9 and CXCL11 were 0.96 (95 % CI: 0.92-1.00) and 0.97 (95 % CI: 0.94-1.00), respectively. The AUCs of CXCL9 and CXCL11 decreased with the advancement of age. The decision curves of CXCL9 and CXCL11 showed net benefits in both centers. CXCL9 and CXCL11 were upregulated in BCG-treated macrophages. Pleural fluid from TPE and conditioned medium from BCG-treated macrophages were chemotactic for Th cells. Anti-CXCL9 or CXCL11 neutralizing antibodies could partly block the chemotactic activity. CONCLUSIONS: Pleural CXCL9 and CXCL11 are potential diagnostic markers for TPE, but their diagnostic accuracy is compromised in elderly patients. CXCL9 and CXCL11 can promote the migration of peripheral Th cells, thus representing a therapeutic target for the treatment of TPE.

Use of tumor markers in distinguishing lung adenocarcinoma-associated malignant pleural effusion from tuberculous pleural effusion.

BACKGROUND: The distinction between lung adenocarcinoma-associated malignant pleural effusion (MPE) and tuberculous pleural effusion (TPE) continues to pose a challenge. This study sought to assess the supplementary value of tumor markers in enabling a differential diagnosis. METHODS: Data concerning tumor markers, which included carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), cancer antigen 153 (CA153), cancer antigen 724 (CA724), neuron-specific enolase (NSE), cytokeratin19 fragment (Cyfra21-1), and squamous cell carcinoma antigen (SCCA), in both serum and pleural effusion samples, were retrospectively compiled from lung adenocarcinoma-associated MPE and TPE patients. A comparative analysis of tumor marker concentrations between the two groups was performed to assess diagnostic utility, followed by a multiple logistic regression to control for confounding variables. RESULTS: While gender, serum CA125 and SCCA, and pleural effusion SCCA manifested comparability between the groups, distinctions were noted in patient age and the concentration of other tumor markers in serum and pleural effusion, which were notably elevated in the MPE group. Multiple logistic regression demonstrated a positive association between the risk of lung adenocarcinoma-associated MPE and levels of CEA and CA153 in serum and pleural effusion, as well as Cyfra21-1 in serum (P < 0.05). The odds ratio for CEA surpassed that of CA153 and Cyfra21-1. CONCLUSIONS: CEA and CA153 in serum and pleural effusion, and Cyfra21-1 in serum emerge as biomarkers possessing supplementary diagnostic value in distinguishing lung adenocarcinoma-associated MPE from TPE. The diagnostic efficacy of CEA is superior to CA153 and Cyfra21-1. Conversely, the utility of CA125, CA724, NSE, and SCCA appears constrained.

Diagnostic accuracy of Lipoarabinomannan detection by lateral flow assay in pleural tuberculosis.

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

Features which discriminate between tuberculosis and haematologic malignancy as the cause of pleural effusions with high adenosine deaminase.

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

Accidental Detection of Tuberculous Empyema at Health Check-Up.

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

Diagnostic and comparative performance for the prediction of tuberculous pleural effusion using machine learning algorithms.

OBJECTIVE: Early diagnosis and differential diagnosis of tuberculous pleural effusion (TPE) remains challenging and is critical to the patients' prognosis. The present study aimed to develop nine machine learning (ML) algorithms for early diagnosis of TPE and compare their performance. METHODS: A total of 1435 untreated patients with pleural effusions (PEs) were retrospectively included and divided into the training set (80%) and the test set (20%). The demographic and laboratory variables were collected, preprocessed, and analyzed to select features, which were fed into nine ML algorithms to develop an optimal diagnostic model for TPE. The proposed model was validated by an independently external data. The decision curve analysis (DCA) and the SHapley Additive exPlanations (SHAP) were also applied. RESULTS: Support vector machine (SVM) was the best model in discriminating TPE from non-TPE, with a balanced accuracy of 87.7%, precision of 85.3%, area under the curve (AUC) of 0.914, sensitivity of 94.7%, specificity of 80.7%, and F1-score of 86.0% among the nine ML algorithms. The excellent diagnostic performance was also validated by the external data (a balanced accuracy of 87.7%, precision of 85.2%, and AUC of 0.898). Neural network (NN) and K-nearest neighbor (KNN) had better net benefits in clinical usefulness. Besides, PE adenosine deaminase (ADA), PE carcinoembryonic antigen (CEA), and serum CYFRA21-1 were identified as the top three important features for diagnosing TPE. CONCLUSIONS: This study developed and validated a SVM model for the early diagnosis of TPE, which might help clinicians provide better diagnosis and treatment for TPE patients.

Diagnostic flowchart for tuberculous pleurisy, pleural infection, and malignant pleural effusion.

BACKGROUND: Several markers for the diagnosis of pleural effusion have been reported; however, a comprehensive evaluation using those markers has not been performed. Therefore, this study aimed to develop a diagnostic flowchart for tuberculous pleurisy, pleural infection, malignant pleural effusion, and other diseases by using these markers. METHODS: We retrospectively collected data from 174 patients with tuberculous pleurisy, 215 patients with pleural infection other than tuberculous pleurisy, 360 patients with malignant pleural effusion, and 209 patients with other diseases at Fukujuji Hospital from January 2012 to October 2022. The diagnostic flowchart for four diseases was developed by using several previously reported markers. RESULTS: The flowchart was developed by including seven markers: pleural ADA ≥40 IU/L, pleural fluid LDH <825 IU/L, pleural fluid ADA/TP < 14, neutrophil predominance or cell degeneration, peripheral blood WBC ≥9200/µL or serum CRP ≥12 mg/dL, pleural amylase ≥75 U/L, and the presence of pneumothorax according to the algorithm of a decision tree. The accuracy ratio of the flowchart was 71.7 % for the diagnosis of the four diseases, with 79.3 % sensitivity and 75.4 % positive predictive value (PPV) for tuberculosis pleurisy, 75.8 % sensitivity and 83.2 % PPV for pleural infection, 88.6 % sensitivity and 68.8 % PPV for malignant pleural effusion, and 33.0 % sensitivity and 60.0 % PPV for other diseases in the flowchart. The misdiagnosis ratios were 4.6 % for tuberculosis pleurisy, 6.8 % for pleural infection, and 8.3 % for malignant pleural effusion. CONCLUSION: This study developed a useful diagnostic flowchart for tuberculous pleurisy, pleural infection, malignant pleural effusion, and other diseases.

Caracterización clínica y microbiológica de pacientes con trazas en Xpert MTB/RIF Ultra / Clinical and microbiological characterization of patients with Xpert MTB/RIF Ultra traces

INTRODUCCIÓN: El Xpert MTB/RIF Ultra (Ultra) ha mejorado dramáticamente el diagnóstico de la tuberculosis (TBC). Con él ha nacido la categoría de trazas, que es la menor carga bacilar detectable por este examen. OBJETIVO: Describir las características clínicas de los pacientes con presencia de trazas en el Ultra y evaluar la confirmación de la TBC como diagnóstico clínico. MATERIALES Y MÉTODOS: Estudio descriptivo de serie de casos. Se extrajo la información de fichas clínicas de pacientes con positividad a trazas. Se confrontaron datos clínicos, microbiológicos e histopatológicos. RESULTADOS: Se analizaron 21 pacientes. La edad promedio fue de 52 años. Todos los casos presentaron baciloscopias negativas. Cuatro cultivos en medio líquido MGIT fueron positivos, dos en pleura parietal, uno en líquido pleural y otro en expectoración. En pleura parietal, tres casos presentaron granulomas con necrosis caseosa y un granuloma esbozos de necrosis. En tejido pulmonar se observaron dos casos con granulomas con esbozos de necrosis y dos con granulomas no necrotizantes. Tres pacientes tenían el antecedente de TBC previa, se interpretó la positividad de trazas en ellos como falsos positivos. Finalmente se diagnosticaron 13 casos como TBC activa, donde cinco de ellos fueron TBC pleurales. La mayor concordancia clínica, microbiológica e histopatológica fue en muestras de líquido y tejido pleural. DISCUSIÓN: Se debe interpretar con cautela los hallazgos de esta prueba en muestras de vía aérea; el análisis multidisciplinario (clínica, imágenes, microbiología, histología) es crucial en las decisiones de nuestras conductas clínicas futuras. El hallazgo de trazas en pleura tiene, a nuestro parecer, un alto valor diagnóstico en el estudio de la tuberculosis en esta localización.

INTRODUCTION: Xpert MTB/RIF Ultra has dramatically changed the diagnosis of tuberculosis. A new category called traces appeared, which is the smallest amount of bacillar load detectable. OBJECTIVE: Describe the clinical characteristics of patients that present traces in Xpert MTB/RIF Ultra test, and to evaluate the confirmation of tuberculosis as clinical diagnosis. METHODS: We perform a descriptive case series study. Information was recovered from clinical records of patients with positive test for traces. Clinical, histopathological and microbiological results were confronted. RESULTS: Twenty one patients were analyzed. The mean age was 52 years-old. All cases had negative smear microscopy and four MGIT cultures were positive, two in pleural fluid and another in sputum. In parietal pleura, three cases presented granulomas with caseous necrosis, and one showed granuloma with very little necrosis. In pleural tissue we observed two cases of granulomas with traces of necrosis and two with non-necrotizing granulomas. Three patients had history of previous tuberculosis and positive traces, the test was interpreted as a false positive result. Finally, active tuberculosis was diagnosed in 13 cases, and five of them were pleural tuberculosis. The highest clinical, microbiological and histopathological agreement was in fluid and pleural tissue samples. DISCUSSION: The findings of Xpert MTB/RIF Ultra in airway samples must be interpreted carefully. Multi-disciplinary analysis is crucial in future clinical decisions. The finding of traces in pleura has, in our opinion, a high diagnostic value in the study of tuberculosis in this location.

Performance of the quantification of adenosine deaminase and determination of the lactate dehydrogenase/adenosine deaminase ratio for the diagnosis of pleural tuberculosis in children and adolescents / Desempenho da quantificação de adenosina desaminase e determinação da relação lactato desidrogenase/adenosina desaminase para o diagnóstico de tuberculose pleural em crianças e adolescentes

ABSTRACT Objective: To evaluate the accuracy of determining the adenosine deaminase (ADA) level, the 2'-deoxyadenosine/ADA ratio, and the LDH/ADA ratio in pleural fluid for the diagnosis of pleural tuberculosis (PT) in children and adolescents. Methods: This was a retrospective cross-sectional study conducted at a tertiary hospital in a high-tuberculosis-incidence area, between 2001 and 2018. All patients with ADA in pleural fluid and a confirmed diagnosis of PT (cPT) or parapneumonic effusion (PPE) were included. Results: The cPT and PPE groups comprised 25 and 68 individuals, respectively. At a cutoff of 40 U/L, ADA measurement showed the following: sensitivity, 88%; specificity, 31%; positive predictive value (PPV), 32%; negative predictive value (NPV), 88%; and overall accuracy, 46%. The best cutoffs were an ADA level of 125 U/L, a 2'-deoxyadenosine/ADA ratio of 0.5, and an LDH/ADA ratio of 8.3, with AUC of 0.67, 0.75, and 0.82, respectively. The sensitivity, specificity, PPV, NPV, and overall accuracy of the 125 U/L ADA cutoff were 84%, 65%, 47%, 92%, and 70%, respectively, compared with 79%, 79%, 59%, 91%, and 79%, respectively, for the 8.3 LDH/ADA ratio cutoff. Changing the LDH/ADA ratio cutoff to 3.0 increased the specificity to 98%. Conclusions: The ADA level and the 2'-deoxyadenosine/ADA ratio are not good biomarkers for the diagnosis of PT in pediatric patients. Determination of the LDH/ADA ratio provides the best overall accuracy for the diagnosis of PT in such patients.

RESUMO Objetivo: Avaliar a acurácia da determinação do nível de adenosina desaminase (ADA), da relação 2'-desoxiadenosina/ADA e da relação LDH/ADA no líquido pleural para o diagnóstico de tuberculose pleural (TP) em crianças e adolescentes. Métodos: Estudo transversal retrospectivo realizado em um hospital terciário em uma área de alta incidência de tuberculose entre 2001 e 2018. Todos os pacientes com determinação de ADA no líquido pleural e com diagnóstico confirmado de TP (TPc) ou de derrame parapneumônico (DPP) foram incluídos. Resultados: Os grupos TPc e DPP foram compostos por 25 e 68 indivíduos, respectivamente. Num ponto de corte de 40 U/L, a medida de ADA mostrou o seguinte: sensibilidade, 88%; especificidade, 31%; valor preditivo positivo (VPP), 32%; valor preditivo negativo (VPN), 88%; e acurácia geral, 46%. Os melhores pontos de corte foram ADA de 125 U/L, relação 2'-desoxiadenosina/ADA de 0,5 e relação LDH/ADA de 8,3, com ASC de 0,67, 0,75 e 0,82, respectivamente. A sensibilidade, especificidade, VPP, VPN e acurácia geral do ponto de corte de 125 U/L para ADA foram de 84%, 65%, 47%, 92% e 70%, respectivamente, em comparação com 79%, 79%, 59%, 91% e 79%, respectivamente, para o ponto de corte de 8,3 para a relação LDH/ADA. Ao alterar o ponto de corte da relação LDH/ADA para 3,0 a especificidade aumentou para 98%. Conclusões: O nível de ADA e a relação 2'-desoxiadenosina/ADA não são bons biomarcadores para o diagnóstico de PT em pacientes pediátricos. A determinação da relação LDH/ADA fornece a melhor acurácia geral para o diagnóstico de PT nesses pacientes.

Historia natural de la tuberculosis pleural en una paciente inmunocompetente / Natural history of pleural tuberculosis in an immunocompetent patient

La tuberculosis es una enfermedad infecciosa por Mycobacterium tuberculosis conocida desde la antigüedad y con gran importancia en la actualidad ubicándose como una de las principales causas de morbimortalidad, puede tener presentación pulmonar y extrapulmonar. Se presenta el caso clínico de una adolescente inmunocompetente con tuberculosis con descripción de la historia natural, a raíz del cual se realiza y presenta una revisión de literatura actual confrontando con artículos de revisiones de temas en búsqueda electrónica en bases de datos de RIMA, MEDLINE, PUBMED, MEDSCAPE, de 2013 a 2018. CONCLUSIONES: Es primordial conocer la presentación extrapulmonar corresponde al 21% de los casos de tuberculosis puede ser asintomático o sintomático con fiebre, tos y dolor pleurítico.

Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis that has been known since antiquity and with great importance at present, being one of the main causes of morbidity and mortality, it can have pulmonary and extrapulmonary presentation. METHOD: review of current literature comparing articles with reviews of subjects in electronic search in databases of RIMA, MEDLINE, PUB-MED, MEDSCAPE, from 2013 to 2018 Clinical case: the clinical case of an immunocompetent adolescent with tuberculosis is represented. description of the natural history CONCLUSIONS: It is essential to know the extrapulmonary presentation corresponds to 21% of cases of tuberculosis can be asymptomatic or symptomatic with fever, cough and pleuritic pain.

Reporte de un caso de quilotórax tuberculoso / A case report of tuberculous chylothorax

El quilotórax tuberculoso es una patología infecciosa infrecuente, que se produce como consecuencia del bloqueo del conducto torácico. Su tratamiento está dirigido a combatir la infección tuberculosa. Se presenta el caso de un varón de 55 años de edad, chofer, natural de Trujillo-Perú, que acudió a emergencia por disnea progresiva y tos seca de cinco días de evolución. El examen físico reveló frémito vocal, matidez y murmullo vesicular disminuido en 2/3 inferiores del hemitórax izquierdo. La radiografía y ecografía torácica evidenciaron derrame pleural significativo, y la toracocentesis reveló quilotórax. Posteriormente, se colocó un tubo de drenaje torácico, con disminución progresiva del volumen del líquido pleural y cambios citoquímicos. Se realizó videobroncoscopía diagnóstica con aspirado broncoalveolar, revelando bacilos ácido-alcohol resistentes. El paciente recibió tratamiento antituberculoso, con evolución favorable. El quilotórax tuberculoso constituye una causa importante de quilotórax a considerar en zonas endémicas de tuberculosis. El tratamiento adecuado de la infección, conlleva a resolución de la enfermedad.

Tuberculous chylothorax is a rare infectious disease that occurs when the thoracic duct is obstructed. Treatment is directed to the tuberculosis infection. A 55-year-old male, driver, born in Trujillo (Peru) is admitted to the emergency department with increasing dyspnea and a 5-day dry cough. The physical examination revealed vocal fremitus, dullness to percussion, and a vesicular murmur that was decreased on the lower 2/3 of the left hemithorax. The X-ray and the thoracic ultrasound revealed significant left pleural effusion. The thoracocentesis drained fluid identified as chylothorax. Subsequently, a thoracic tube was placed, with a decrease in pleural fluid volume and later normalization of the cytochemical changes. Diagnostic video bronchoscopy was performed with a bronchoalveolar aspirate, revealing acid-fast bacilli. The patient received antituberculosis treatment with a favorable outcome. Tuberculous chylothorax is an important cause of chylothorax to be considered in endemic areas of tuberculosis. Proper treatment of the infection leads to resolution of the disease.

Tuberculosis pleural en paciente pediátrico: reporte de un caso y revisión de la literatura / Pleural tuberculosis in a pediatric patient: case report and review

Tuberculosis (TB) is a common cause of pleural effusion in young people from endemic areas. Among the forms of extrapulmonary TB in people with immunodeficiencies, the most frequent localization is the pleura. The use of immunological and molecular biology tests for the diagnosis of TB in pleural fluid and other locations with high sensitivity and specificity is highlighted. We present a clinical case with the objective of giving an overview of the treatment of the patient with suspected pleural tuberculosis

La Tuberculosis (TB) es una causa común de derrame pleural en jóvenes en zonas endémicas. Dentro de las formas de TB extrapulmonar en personas que cursan con inmunodeficiencias, la localización más frecuente es la TB pleural. Se destaca el uso de las pruebas inmunológicas y de biología molecular para el diagnóstico de TB en líquido pleural y de otras localizaciones con una elevada sensibilidad y especificidad. Se presenta un caso clínico con el objetivo de describir una visión general del abordaje del paciente con sospecha de tuberculosis pleural

Real-time PCR assay for the diagnosis of pleural tuberculosis / Reacción en cadena de la polimerasa en tiempo real para el diagnóstico de tuberculosis pleural

Abstract Introduction: The diagnosis of pleural tuberculosis requires an invasive and time-consuming reference method. Polymerase chain reaction (PCR) is rapid, but validation in pleural tuberculosis is still weak. Objective: To establish the operating characteristics of real-time polymerase chain reaction (RT-PCR) hybridization probes for the diagnosis of pleural tuberculosis. Methods: The validity of the RT-PCR hybridization probes was evaluated compared to a composite reference method by a cross-sectional study at the Hospital Universitario de la Samaritana. 40 adults with lymphocytic pleural effusion were included. Pleural tuberculosis was confirmed (in 9 patients) if the patient had at least one of three tests using the positive reference method: Ziehl-Neelsen or Mycobacterium tuberculosis culture in fluid or pleural tissue, or pleural biopsy with granulomas. Pleural tuberculosis was ruled out (in 31 patients) if all three tests were negative. The operating characteristics of the RT-PCR, using the Mid-P Exact Test, were determined using the OpenEpi 2.3 Software (2009). Results: The RT-PCR hybridization probes showed a sensitivity of 66.7% (95% CI: 33.2%-90.7%) and a specificity of 93.5% (95% CI: 80.3%-98.9%). The PPV was 75.0% (95% CI: 38.8%-95.6%) and a NPV of 90.6% (95% CI: 76.6%-97.6%). Two false positives were found for the test, one with pleural mesothelioma and the other with chronic pleuritis with mesothelial hyperplasia. Conclusions: The RT-PCR hybridization probes had good specificity and acceptable sensitivity, but a negative value cannot rule out pleural tuberculosis.

Resumen Introducción: El diagnóstico de tuberculosis pleural requiere un método de referencia invasivo y demorado. La reacción en cadena de la polimerasa es rápida, pero su validación en tuberculosis pleural aún es débil. Objetivo: Establecer las características operativas de la reacción en cadena de la polimerasa en tiempo real (RT-PCR) sondas de hibridación para el diagnóstico de tuberculosis pleural. Métodos: Se evaluó la validez de la RT-PCR sondas de hibridación comparada con un método de referencia compuesto mediante un estudio transversal en el Hospital Universitario de la Samaritana. Se incluyeron 40 adultos con derrame pleural linfocitario. Tuberculosis pleural fue confirmada (en 9 pacientes) si el paciente tenía mínimo una de tres pruebas del método de referencia positiva: Ziehl-Neelsen o cultivo para Mycobacterium tuberculosis en líquido o tejido pleural, o biopsia pleural con granulomas; se descartó tuberculosis pleural (en 31 pacientes) si las tres pruebas eran negativas. Se determinaron las características operativas de la RT-PCR, mediante la Prueba Mid-P Exact, con el Software OpenEpi 2.3 (2009). Resultados: La RT-PCR sondas de hibridación mostró una sensibilidad del 66.7% (IC 95%: 33.2%-90.7%) y una especificidad del 93.5% (IC 95%: 80.3%-98.9%). El VPP fue de 75.0% (IC 95%: 38.8%-95.6%) y un VPN de 90.6% (IC 95%: 76.6%-97.6%). Se encontraron dos falsos positivos para la prueba, uno con mesotelioma pleural y otro con pleuritis crónica con hiperplasia mesotelial. Conclusiones: La RT-PCR sondas de hibridación tuvo una buena especificidad y una aceptable sensibilidad, pero un valor negativo no puede descartar tuberculosis pleural.