Search

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.

Objectives. This study aims to investigate the diagnostic value of 18F-FDG PET/CT in tuberculous pleurisy (TBP) and the differential diagnostic value of 18F-FDG PET/CT between TBP and pleural metastasis from lung adenocarcinoma (PMLAC). Materials and Methods. The features of pleura on PET and hybrid CT were retrospectively studied in 20 patients with TBP and 32 patients with PMLAC. The ROC curve was used to evaluate the diagnostic effectiveness of these indices for TBP and PMLAC, and binary logistic regression analysis was conducted to identify independent predictors of TBP and PMLAC. Results. There were significant differences in pleural 18F-FDG uptake pattern on PET ( P = 0.001 ), pleural morphology pattern on CT ( P = 0.002 ), the maximum diameter of the pleural nodule ( P = 0.001 ), and interlobular fissure nodule ( P = 0.001 ) between TBP and PMLAC groups. The diffused pleural FDG uptake type on PET (odds ratio (OR) = 6.0, 95% CI 2.216–16.248, P = 0.001 ) and the lamellar pleural thickening type on CT (OR = 4.4, 95% CI 2.536–7.635, P = 0.001 ) were independent predictors of TBP, with 60% and 55% sensitivity, 96.6% and 90.6% specificity, and 82.7% and 77.0% accuracy. The combined diagnostic sensitivity, specificity, and accuracy for TBP were 70%, 87.5%, and 80.8%. The mixed pleural FDG uptake type on PET (OR = 5.106, 95% CI 2.024–12.879, P = 0.001 ), the mixed pleural thickening type on CT (OR = 2.289, 95% CI 1.442–3.634, P = 0.001 ), and the maximum diameter of the pleural nodule (OR = 1.027, 95% CI 1.012–1.042, P = 0.001 ) were independent predictors of PMLAC, with 78.1%, 71.9%, and 87.5% sensitivity, 85%, 80%, and 85% specificity, and 80.8%, 75%, and 86.5% accuracy. The combined diagnostic sensitivity, specificity, and accuracy for PMLAC were 96.9%, 85%, and 90.4%. Conclusions. 18F-FDG PET/CT is of great clinical value in the diagnosis of TBP and in the differential diagnosis between TBP and PMLAC.

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

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

Necrotizing sarcoid granulomatosis (NSG) is a rare inflammatory disease. Although considered by some to be a subtype of sarcoidosis, this opinion is not universal. NSG is histologically characterized by the presence of necrotizing sarcoid like granuloma and granulomatous vasculitis. The exclusion of potential etiologies for necrotizing granulomatous inflammation is necessary to establish a diagnosis of NSG. A 70-year old female presented to our office after she was incidentally found to have a right lung cavitary lesion on a shoulder X-ray. She had an extensive serologic workup for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, mycobacterial and fungal etiologies, but they were all negative. She subsequently underwent bronchoscopic evaluation and biopsies. The histopathologic analysis revealed sarcoid-like granulomatous inflammation with large necrosis and mild granulomatous vasculitis. The pulmonary function test revealed a restrictive ventilatory defect. The patient was treated with steroid therapy with rapid radiologic and spirometric improvement.

Background/Aims: Pleural fluid adenosine deaminase (ADA) levels are useful in discriminating tuberculous pleural effusions (TPEs) from malignant pleural effusions (MPEs). However, some patients with MPE exhibit high-ADA levels, which may mimic TPEs. There is limited data regarding the differential diagnosis between high-ADA MPE and high-ADA TPE. This study aimed to identify the predictors for distinguishing high-ADA MPEs from high-ADA TPEs.Methods: Patients with TPE and MPE with pleural f luid ADA levels ≥ 40 IU/L were included in this study. Clinical, laboratory, and radiological data were compared between the two groups. Independent predictors and their diagnostic performance for high-ADA MPEs were evaluated using multivariate logistic regression analysis and receiver operating characteristic curve.Results: A total of 200 patients (high-ADA MPE, n = 30, and high-ADA TPE, n = 170) were retrospectively included. In the multivariate analysis, pleural fluid ADA, pleural f luid carcinoembryonic antigen (CEA), and pleural nodularity were independent discriminators between high-ADA MPE and high-ADA TPE groups. Using pleural ADA level of 40 to 56 IU/L (3 points), pleural CEA level ≥ 6 ng/mL (6 points), and presence of pleural nodularity (3 points) for predicting high-ADA MPEs, a sum score ≥ 6 points yielded a sensitivity of 90%, specificity of 96%, positive predictive value of 82%, negative predictive value of 98%, and area under the receiver operating characteristic curve of 0.965.Conclusions: A scoring system using three parameters may be helpful in guiding the differential diagnosis between high-ADA MPEs and high-ADA TPEs.

Pleural tuberculosis (TB) is common and often follows a benign course but may result in serious long-term morbidity. Diagnosis is challenging because of the paucibacillary nature of the condition. Advances in Mycobacterium culture media and PCR-based techniques have increased the yield from mycobacteriologic tests. Surrogate biomarkers perform well in diagnostic accuracy studies but must be interpreted in the context of the pretest probability in the individual patient. Confirming the diagnosis often requires biopsy, which may be acquired through thoracoscopy or image-guided closed pleural biopsy. Treatment is standard anti-TB therapy, with optional drainage and intrapleural fibrinolytics or surgery in complicated cases.

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. 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. 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. 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 ( 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. Die Diagnostik der tuberkulösen Pleuritis gestaltet sich aufgrund der bakterienarmen Natur der Erkrankung schwierig. Die internistische Thorakoskopie gilt nach wie vor als diagnostischer Goldstandard bei tuberkulöser Pleuritis. Ziel der Studie war es, die diagnostische Aussagekraft des Sago-artigen Thorakoskopie-Erscheinungsbilds der Pleura in Hinblick auf Tuberkulose unter Heranziehung der histopathologischen, Gewebe-Mykobakterien-Kultur- und Gewebe-Xpert MTB/Rif-Assay-Befunde zu klären. Alle konsekutiven Patienten mit lymphozytärem, exsudativem Pleuraerguss, die die Einschlusskriterien der Studie erfüllten, unterzogen sich einer internistischen Thorakoskopie unter Lokalanästhesie. Das dabei entnommene Pleuragewebe wurde zur histopathologischen Untersuchung, Mykobakterien-Kultur und Xpert MTB/Rif-Untersuchung eingeschickt. Der histopathologische Befund einer chronischen granulomatösen Entzündung und das Ansprechen auf eine antituberkulöse Therapie wurden als Referenzstandard verwendet, um die Diagnose der tuberkulösen Pleuritis zu sichern. Insgesamt wurden 249 Patienten in die Studie aufgenommen, von denen 168 einen tuberkulosebedingten Erguss aufwiesen. Für den Thorakoskopiebefund Sago-artiger Knötchen fand sich eine Sensitivität von 58,9 %, eine Spezifität von 92,6 % und eine diagnostische Genauigkeit von 69,88 % bei tuberkulöser Pleuritis. Das Vorliegen Sago-artiger Knötchen ist stark mit dem Nachweis von Mycobacterium tuberculosis im Xpert MTB/Rif-Assay und in der Mykobakterien-Kultur der Pleura assoziiert (p-Wert 0,007). Sago-artige Knötchen der Pleura haben einen hohen positiv prädiktiven Wert für tuberkulöse Pleuritis. In Länder mit hochgradig endemischer Tuberkulose kann bei Patienten mit diesem Thorakoskopiebefund die antituberkulöse Therapie schon vor Erhalt der Ergebnisse der histopathologischen Untersuchung oder Mykobakterien-Kultur eingeleitet werden.

Pleural effusion(PE) is a common medical problem with various causes. The differential diagnosis for PE is often challenging. This consensus was generated by members of the academic group of the pleural and mediastinal diseases(preparatory) of Chinese Thoracic Society and some external experts. The members convened in virtual meetings and conducted an extensive literature investigation and assessed the quality of the evidence using a modified grading of recommendations assessment, development, and evaluation(GRADE) approach. This consensus included three chapters: the initial evaluation of PE, the diagnosis of PE with common causes, and the diagnosis of PE with uncommon causes.The main recommendations of Chapter Ⅰ were as follows:(1) For patients suspected of PE according to medical history and clinical manifestations, thoracic CT or ultrasound is recommended to confirm the presence or absence of PE.(2) Ultrasound-guided thoracentesis is recommended when available. Recommended tests for all sampled pleural effeusions include total protein, lactate dehydrogenase (LDH), adenosine deaminase (ADA), differential cell count, and cytological examination.(3) It is recommended to use Light's criteria to distinguish exudate and transudate. When PE is classified to be exudates with heart failure, it is recommended to detect N-terminal pro-brain natriuretic peptide of PE or serum-pleural fluid albumin gradient to assist the judgment.(4) Pleural biopsy is recommended for patients for whom the causes of PE cannot be identified by the detection of PE samples, and CT or ultrasound-guided pleural biopsy is more accurate. Thoracoscopy is recommended for patients whose etiology cannot be identified by laboratory tests of PE and/or pleural biopsy histopathology.The main recommendations of Chapter Ⅱ were as follows:(1)It is suggested to obtain more samples or use immunocytochemistry to assist the diagnosis and cell typing when initial cytopathology examination shows atypical cells, suspicious malignant or malignant cells. (2) Liquid medium for胸腔积液是多种疾病常见的并发症，其病因诊断具有挑战性。中华医学会呼吸病学分会胸膜与纵隔疾病学组（筹）组织专家，充分评估了胸腔积液诊断领域最新的研究结果，基于GRADE证据分级的原则，经过多次会议讨论和修订，最终形成了胸腔积液诊断的专家共识。本共识分为三章：胸腔积液的评估和检测、常见病因胸腔积液的诊断、其他类型胸腔积液的诊断。第一章主要推荐意见如下：（1）根据病史和临床表现怀疑为胸腔积液的患者，推荐行胸部CT和（或）胸腔超声检查明确有无胸腔积液。（2）有条件情况下，推荐在超声引导下行胸腔穿刺。诊断性胸腔穿刺，建议至少检测胸腔积液总蛋白、乳酸脱氢酶、腺苷脱氨酶、细胞分类计数和细胞病理。（3）建议用Light标准来区分渗出液和漏出液；部分漏出液经Light标准可能被误判为渗出液；如果存在心脏疾病，而胸腔积液判断为渗出液，建议检测胸腔积液N-端脑钠肽前体或血清-胸腔积液白蛋白梯度协助判断。（4）针对胸腔积液样本检测未能明确病因的患者，推荐行胸膜活检，CT或超声引导下胸膜活检准确性更高。经胸腔积液实验室检测和（或）胸膜活检未能明确病因者，建议行胸腔镜检查。第二章主要推荐意见如下：（1）胸腔积液细胞病理显示为异型细胞、可疑恶性或恶性细胞，建议获取更多样本或通过免疫细胞化学协助确诊及分型。（2）建议用液体培养基进行结核分枝杆菌（MTB）培养以提高阳性率。推荐在疑诊结核性胸腔积液时进行分子诊断（核酸扩增或Xpert MTB/RIF）。疑诊结核性胸腔积液而胸腔积液检查未能确诊者，推荐行CT或超声引导下胸膜活检或胸腔镜获取胸膜组织行抗酸染色、结核分枝杆菌核酸扩增和培养。（3）推荐检测胸腔积液C反应蛋白协助鉴别非复杂性肺炎旁胸腔积液（PPE）和复杂性PPE。对PPE和脓胸患者，建议将胸腔积液接种到血液培养瓶中，或将超声引导下胸膜活检的标本进行培养，提高培养阳性率。第三章主要推荐意见如下：（1）如果胸腔积液不能用常见病因解释，建议综合分析患者的病史、临床表现、积液特征和活检病理结果等，以排查少见和罕见病因。（2）临床疑诊乳糜胸或假性乳糜胸，推荐检测胸腔积液中是否存在乳糜微粒或胆固醇晶体，并检测胸腔积液甘油三酯和胆固醇水平。（3）胸腔积液可能是多种病因共同作用的结果，对伴胸腔积液的重症患者，建议排查心力衰竭、低蛋白血症、胸腔感染等因素。（4）对于经胸腔镜胸膜活检仍未明确病因的胸腔积液患者，建议密切随访至少2年以排除恶性疾病。.

Nicotinamide phosphoribosyltransferase (NAMPT) has been reported to be involved in infectious diseases, but it is unknown whether it plays a role in infectious pleural effusions (IPEs). We observed the levels of NAMPT in pleural effusions of different etiologies and investigated the clinical value of NAMPT in the differential diagnosis of infectious pleural effusions. A total of 111 patients with pleural effusion were enrolled in the study, including 25 parapneumonic effusions (PPEs) (17 uncomplicated PPEs, 3 complicated PPEs, and 5 empyemas), 30 tuberculous pleural effusions (TPEs), 36 malignant pleural effusions (MPEs), and 20 transudative effusions. Pleural fluid NAMPT levels were highest in the patients with empyemas [575.4 (457.7, 649.3) ng/ml], followed by those with complicated PPEs [113.5 (103.5, 155.29) ng/ml], uncomplicated PPEs [24.9 (20.2, 46.7) ng/ml] and TPEs [88 (19.4, 182.6) ng/ml], and lower in patients with MPEs [11.5 (6.5, 18.4) ng/ml] and transudative effusions [4.3 (2.6, 5.1) ng/ml]. Pleural fluid NAMPT levels were significantly higher in PPEs (P

Background To investigate the correlation between pleural fluid interleukin-33 (IL-33) and adenosine deaminase (ADA) and peripheral blood tuberculosis T cell spot detection (T-SPOT.TB), and the combined value of the three tests for the diagnosis of tuberculous pleurisy. Methods 79 patients with pleural effusion admitted from June 2017 to December 2018 were enrolled. They were divided into tuberculous pleural effusion (TPE) group (57 cases, 72.2%) and malignant pleural effusion group (17 cases, 21.5%), pneumonia-like pleural effusion group (5 cases, 6.3%). Correlation between pleural fluid IL-33, pleural effusion ADA and peripheral blood T-SPOT.TB was analyzed, comparison of the three separate and combined diagnostic efficacy was also performed. Results The levels of IL-33, ADA and peripheral blood T-SPOT.TB in patients with TPE were significantly higher than those in non-TPE (P Conclusion Combined detection of pleural effusion IL-33, ADA and peripheral blood T-SPOT.TB can improve the diagnostic efficacy of tuberculous pleurisy.

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.

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

Introduction Residual pleural opacity (RPO) is a common radiographic sequela in patients with tubercular pleural effusion at the end of the treatment. This study was designed to find out the risk factors associated with residual pleural opacity (RPO). Materials & methods This was a prospective longitudinal study performed to analyse data of 56 patients (46 males & 10 females) who were diagnosed as tubercular pleural effusion and treated for the same between 1st Jan 2019 to 30th March 2020. Chest X-ray posteroanterior & Lateral view was done (performed) at 0 and 6 months of treatment to quantify the amount of pleural effusion and measured the residual pleural opacity at the end of the treatment. RPO included both non resolving pleural effusion as well as residual pleural thickening (RPT). All statistical analysis was done using SPSS version 20.0 (SPSS Inc., Chicago, IL, USA). Multivariate logistic regression was performed to explore the association of risk factors and Residual pleural opacity. The statistical significance level was set at 0.05 (two-tailed). Results The incidence of Residual pleural opacity (RPO) at the end of 6 months of antituberculosis treatment was 53.57% (30/56)). The study patients were divided into RPO and non- RPO group. Male gender had significantly higher incidence of RPO (93.3% vs 69.2% P = 0.01)). Patients with RPO group had significantly more cough and weight loss as compared to non RPO group (96.6% vs 65.3% P = 0.002 and 60% vs 23% P = 0.005). The proportion of patients who underwent therapeutic aspiration and gained weight of more than 5kg during treatment (19.5% vs 7.6% P = 0.02 & 46.6% vs 7.6% P = 0.001) was significantly higher in RPO group. A significantly lower protein, glucose and higher LDH level in pleural fluid was observed in the RPO group compared to non-RPO group (P = 0.006, P = 0.01, P = 0.001)). No significant difference was found in the pleural fluid ADA, lymphocyte, neutrophil levels between the two groups (p > 0.05). Logistic regression analysis showed that the male gender, low pleural fluid glucose, presence of cough and weight loss were associated with significantly increased risk of residual pleural opacity and thickening (p Conclusion Tubercular pleural effusion is associated with residual pleural opacity in more than half of the patients. Male gender and low glucose levels in pleural fluid was associated with increased risk of residual pleural opacity.

Current standard of care for treatment of CML is based on tyrosine kinase inhibitors (TKI's). Imatinib is most frequently used first line tyrosine kinase inhibitor. Various side effects of TKI's are known, but some may still be unknown. We are reporting three cases of CML who developed tuberculosis while on treatment with imatinib or dasatinib. Two cases developed CNS tuberculosis and other one was tubercular pleural effusion. These cases indicate that imatinib and other TKI's probably interfere with immunological functions and predispose patients for tuberculosis.

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. Method: 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. Result: 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. Conclusion: 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 A pleural fluid adenosine deaminase (ADA) has been used globally to assist in the diagnosis of a tuberculous pleural effusion (TPE) with a notable negative predictive value. Case presentation We report a case of a patient with a negative pleural fluid ADA who was found to have culture-positive and biopsy-proven Mycobacterium tuberculosis. Conclusions This case shows the importance of pursuing gold standard diagnostic studies when clinical suspicion remains high despite negative preliminary testing. We further describe gaps in research to improve pleural fluid biomarkers for TPE.

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.

Background Tuberculous pleural effusion (TPE) patients usually have elevated D-dimer levels. The diagnostic performance of D-dimer in predicting pulmonary embolism (PE) in the TPE population is unclear. This study aimed to assess the diagnostic performance of D-dimer for PE in the TPE population and explore its potential mechanism. Methods We retrospectively analysed patients who were admitted to Xinhua Hospital and Weifang Respiratory Disease Hospital with confirmed TPE between March 2014 and January 2020. D-dimer levels were compared between patients with and without PE. To test the diagnostic performance of D-dimer in predicting PE, receiver operating characteristic curve analysis was performed. Positive predictive value (PPV) and negative predictive value (NPV) were also reported. To explore the potential mechanism of PE in TPE, inflammatory biomarkers were compared between PE and non-PE patients. Results This study included 248 patients (170 males and 78 females) aged 43 ± 20.6 years. Elevated D-dimer levels (≥ 0.5 mg/L) were detected in 186/248 (75%) patients. Of the 150 patients who underwent computed tomography pulmonary angiography, 29 were diagnosed with PE. Among the TPE population, the PE patients had significantly higher D-dimer levels than the non-PE patients (median, 1.06 mg/L vs. 0.84 mg/L, P P 9/L vs. 6.1 × 109/L, P P P Conclusions D-dimer is an objective biomarker for predicting PE in patients with TPE. A D-dimer cut-off of 1.18 mg/L in the TPE population may reduce unnecessary radiological tests due to its excellent sensitivity, specificity, and NPV for PE. The imbalance of prothrombotic and antithrombotic cytokines may partly be attributed to the formation of pulmonary emboli in patients with TPE.

Accurate differential diagnosis is the key to choosing the correct treatment for pleural effusion. The present study aimed to assess whether interleukin 32 (IL-32) could be a new biomarker of tuberculous pleural effusion (TPE) and to explore the biological role of IL-32 in TPE. IL-32 levels were evaluated in the pleural effusions of 131 patients with undetermined pleural effusion from Wuhan and Beijing cohorts using an enzyme-linked immunosorbent assay method. Macrophages from TPE patients were transfected with IL-32-specific small interfering RNA (siRNA), and adenosine deaminase (ADA) expression was determined by real-time PCR and colorimetric methods. With a cutoff value of 247.9 ng/mL, the area under the curve of the receiver operating characteristic (ROC) curve for IL-32 was 0.933 for TPE, and the sensitivity and specificity were 88.4% and 93.4%, respectively. A multivariate logistic regression model with relatively good diagnostic performance was established. IL-32-specific siRNA downregulated ADA expression in macrophages, and IL-32γ treatment significantly induced ADA expression. Our results indicate that IL-32 in pleural effusion may be a novel biomarker for identifying patients with TPE. In addition, our multivariate model is acceptable to rule in or rule out TPE across diverse prevalence settings. Furthermore, IL-32 may modulate ADA expression in the tuberculosis microenvironment. (This study has been registered at ChiCTR under registration number ChiCTR2100051112 [https://www.chictr.org.cn/index.aspx].)

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

Exudative pleural effusion includes tuberculous pleural effusion (TPE), parapneumonic pleural effusion (PPE), and malignant pleural effusion (MPE). An elevated pleural fluid adenosine deaminase (ADA) typically implies TPE, but the rule may not apply to every individual case. Recent studies proposed that the pleural fluid lactate dehydrogenase (LDH)-to-ADA ratio showed a higher diagnostic power than pleural fluid ADA alone in differentiating the etiology of pleural effusion. Hence, we aimed to investigate the performance of pleural fluid LDH-to-ADA ratio as a biomarker in assistance with the diagnosis of TPE, PPE, and MPE. All patients who underwent thoracentesis for the first time with a pleural fluid ADA40 U/L were included in this retrospective study. The clinical data including pleural fluid ADA and LDH-to-ADA ratio were analyzed. A total of 311 patients were enrolled during the study interval. The pleural fluid LDH-to-ADA ratio14.2 (sensitivity: 74.2%; specificity: 90.4%) favored TPE, while the pleural fluid LDH-to-ADA ratio14.5 (sensitivity: 79.9%; specificity: 78.5%) favored PPE. Besides, the pleural fluid LDH-to-ADA ratio46.7 (sensitivity: 56.3%; specificity: 78.3%) favored MPE owing to primary lung cancers. In conclusion, the pleural fluid LDH-to-ADA ratio was an effective indicator in differentiating the etiology of pleural effusions in the cases of high ADA level in the pleural fluid.

Most of pleural effusions are caused by tuberculosis and malignant tumor. Difficult sampling and bacterial sparing nature of these diseases challenge doctors' diagnosis in China. This study aimed to develop a new convenient and effective method for the differentiation of tuberculous and malignant pleural effusion. A prospective cohort study of patients hospitalized with malignant (n = 90) and tuberculous (n = 130) pleural effusions from September 2018 to October 2020 was performed. The diagnostic performance of the age to pleural fluid ADA ratio (age/ADA) and other indicators to distinguish tuberculous and malignant pleural effusions was evaluated by receiver operating characteristic (ROC) curve analysis. The areas under the curve (AUC) of age/ADA and pleural fluid ADA were largest. Age/ADA showed sensitivity and specificity of 81.5% (95%CI 73.8%-87.8%) and 97.8% (95%CI 92.2%-99.7%) respectively. The sensitivity and specificity of pleural fluid ADA were 83.1% (95%CI 75.5%-89.1%) and 93.3% (95%CI 86.1%-97.5%) respectively. The positive likelihood [36.69 (95%CI 9.3-144.8)] of age/ADA was significantly higher than that of pleural fluid ADA [12.46 (95%CI 5.7-27.1)]. The AUCs for Cancer Ratio and Cancer Ratio plus were lower and showed a sensitivity of 80.0% (95%CI 72.1%-86.5%), 80.0% (95%CI 70.2%-87.7%) and a specificity of 81.5% (95%CI 73.8%-87.8%), 80.0% (95%CI 70.2%-87.7%) respectively. Age/ADA has a higher diagnostic accuracy than ADA. Age/ADA is a promising diagnostic index for tuberculous and malignant pleural effusion with high sensitivity and specificity, especially the high positive likelihood ratio. The diagnostic accuracy of Cancer Ratio and Cancer Ratio plus are inferior to those of age/ADA and ADA.

Pleural tuberculosis (TB) is the archetype of extrapulmonary TB (EPTB), which mainly affects the pleural space and leads to exudative pleural effusion. Diagnosis of pleural TB is a difficult task predominantly due to atypical clinical presentations and sparse bacillary load in clinical specimens.We reviewed the current literature on the globally existing conventional/latest modalities for diagnosing pleural TB. Bacteriological examination (smear/culture), tuberculin skin testing/interferon-γ release assays, biochemical testing, imaging and histopathological/cytological examination are the main modalities. Moreover, nucleic acid amplification tests (NAATs),Routine tests are not adequate for effective pleural TB diagnosis. The latest molecular/immunological tests as discussed above, and the other tools

During the COVID-19 pandemic, there have been an increasing number of COVID-19 patients with cavitary or cystic lung lesions, re-positive or long-term positive nucleic acid tests, but the mechanism is still unclear. Lung cavities may appear at long time interval from initial onset of coronavirus infection, generally during the absorption phase of the disease. The main histopathological characteristic is diffuse alveolar damage and may have more severe symptoms after initial recovery from COVID-19 and an increased mortality rate. There are many possible etiologies of pulmonary cavities in COVID-19 patients and we hypothesize that occult SARS-CoV-2, in the form of biofilm, is harbored in the airway lacuna with other pathogenic microorganisms, which may be the cause of pulmonary cavities and repeated and long-term positive nucleic acid tests.

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

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

Background Tuberculous pleural effusion (TPE) is usually characterized by lymphocytic predominance and high pleural fluid adenosine deaminase (pfADA), while parapneumonic pleural effusion (PPE) is usually characterized by neutrophilic predominance. However, in some cases, neutrophils can be predominant in TPE. In such cases, the differential diagnosis between TPE and PPE is challenging and has been rarely investigated. The aim of this study was to evaluate the accuracy of pfADA, pleural fluid lactate dehydrogenase (pfLDH) and other parameters, such as age/pfADA in the differential diagnosis of neutrophil-predominant TPE (NP-TPE) and PPE. Methods Between January 2003 and August 2018, 19 patients with NP-TPE and 54 patients with PPE at Shanghai Jiao Tong University Affiliated Sixth People's Hospital were retrospectively reviewed. Age, blood and pleural fluid findings, and eight ratios that consisted of routine biomarkers were compared between the two groups in ≤50 and >50 years old groups. ROC curve analysis was used to evaluate diagnostic performance. Results The three parameters with the largest AUC were age/pfADA, pfADA and pfLDH in ≤ 50 years old group, and pfADA, age/pfADA and the percentage of neutrophils in pleural fluid (pfN%) in >50 years old group. For patients ≤ 50 years old, pfADA combined with pfLDH or age/pfADA combined with pfLDH could increase the specificity to 100%, while the sensitivity of the former was high (84.6% vs 76.9%). For patients >50 years old, both pfADA combined with pfN% and age/pfADA combined with pfN% could increase the specificity to 90.3% with the same sensitivity. Conclusions Although pfADA played an important role in the discrimination of NP-TPE from PPE, combining pfADA with pfLDH for patients ≤50 years old or combining pfADA with pfN% for patients >50 years old might improve diagnostic performance.

Background Immunoglobulin G4 (IgG4)-related disease is a chronic inflammatory disease that was recognized in 2011. Pleuritis associated with IgG4-related disease is rare and can be difficult to diagnose. Although there have been previous reports on pleuritis associated with IgG4-related disease by thoracoscopic findings, this is the first to observe pleuritis with IgG4-related disease from normal pleural thoracoscopic findings. Case presentation A 70-year-old Japanese female treated for breast cancer 33 years ago was referred to our hospital complaining of dyspnea on exertion. Chest computed tomography (CT) revealed left pleural effusion that was exudative and predominant with lymphocytes, elevated adenosine deaminase (ADA) and Class III cytology (malignancy suspected). Subsequently, thoracoscopic pleural biopsy was performed for definitive diagnosis. Although pleural macroscopic findings appeared normal, we performed pleural biopsy at random sites. This patient was negative for mycobacterium tuberculosis, and neither granulomas nor malignant cells were found in the collected specimens. An infiltration of inflammatory cells, mainly plasma cells and lymphocytes, was observed. Immunostaining revealed the number of IgG4-positive plasma cells was 102/high power field (HPF), and the percentage of IgG4 positive/immunoglobulin G (IgG)-positive cells was 41.4%. Since IgG4 serum levels were high and IgG4-related submandibular sialadenitis was also observed, a definitive diagnose of pleuritis associated with IgG4-related disease was confirmed. Conclusions We diagnosed pleuritis associated with IgG4-related disease by thoracoscopic pleural biopsy samples taken from a visually normal pleura. Although exudative pleural effusion with high ADA and lymphocyte predominance is a characteristic of tuberculous pleuritis, other diseases might be present. Since thoracoscopy can increase the diagnostic yield, pleural biopsy should be considered even if thoracoscopic pleural findings are deemed normal.

Introduction Diagnosing tuberculous pleurisy is important in Japan because it currently has a moderate tuberculosis prevalence. However, physicians often have difficulty making a diagnosis. It was reported that thoracoscopy under local anesthesia is useful for the diagnosis of tuberculous pleurisy, but there are no reports focusing on elderly patients. Methods In this study, the usefulness of thoracoscopy under local anesthesia was evaluated in elderly patients. Among 170 patients who underwent thoracoscopy under local anesthesia at our hospital during 11 years from January 2008 to December 2018, those aged 75 years or older (n = 75) were investigated retrospectively. Results A total of 55 patients underwent thoracoscopy under local anesthesia for detailed examination of pleural effusion of unknown cause. Of these, 18 were diagnosed as tuberculous pleurisy. The median age was 82 years (range: 75–92 years). The diagnosis of tuberculous pleurisy was made in 11 patients in whom Mycobacterium tuberculosis was detected and in four patients whose pathological findings indicated epithelioid granuloma accompanied by caseous necrosis. Clinical diagnosis was made in the remaining three patients based on thoracoscopic findings of the pleural cavity and a high level of adenosine deaminase in pleural fluid. No serious complications attributable to the examination were observed in any patient. Conclusions Thoracoscopy under local anesthesia was useful for the diagnosis of tuberculous pleurisy in elderly patients, with useful information being also obtained for the treatment of tuberculosis.

Background: Establishing the etiology of exudative pleural effusions in the setting of an unrewarding pleural fluid analysis often requires biopsies from the parietal pleura. However, it may be noted that diagnosis such as pulmonary embolism and connective tissue diseases can result in an exudative pleural effusion where a pleural biopsy can yield nonspecific results. Medical thoracoscopy (MT) is a minimally invasive procedure performed under local anesthesia or moderate sedation with excellent yield and favorable safety profile. We analyzed the diagnostic yield of MT for exudative pleural effusions after employing a rigid diagnostic algorithm. The study was undertaken to ascertain the yield of MT in establishing the diagnosis in diagnosis of exudative pleural effusions, to find out the relative contribution of pleural tuberculosis (TB) as a cause of undiagnosed exudative pleural effusion, to describe the etiology of undiagnosed exudative pleural effusion in patients undergoing MT and to determine the correlation between pleural fluid adenosine deaminase (ADA) levels and TB pleuritis in patients undergoing MT. Methods: This was a retrospective study. Patients with undiagnosed exudative pleural effusion were included in the study. MT was performed with semirigid thoracoscope (Olympus LTF 160) under local anesthesia and conscious sedation. Gross appearance and ADA level of pleural fluid were noted. Pleural biopsy material was subjected to histopathology examination and culture for mycobacteria along with cartridge-based nucleic acid amplification test for TB. The yield of MT for establishing the etiology of pleural effusion and the relative contribution of tuberculous pleuritis as a cause of undiagnosed pleural effusion was ascertained. Correlation of pleural fluid ADA levels was done with a final diagnosis of TB pleuritis in patients undergoing MT. Results: Twenty-five patients with undiagnosed exudative pleural effusion underwent thoracoscopy of which 16 were male and 9 were female. MT was able to establish the diagnosis in all cases, providing a diagnostic yield of 100%. Histopathological examination of biopsy specimens yielded a diagnosis of malignant involvement of pleura in 10 patients and granulomatous pleuritis consistent with TB in 14 patients. Pleural TB contributed to 60% of undiagnosed pleural effusions in the present study. The mean ADA value among those who turned positive was 56.338 and 35.300 among those who turned negative using genexpert, which was found to be statistically significant. A value of 31 IU/L showed a sensitivity of 93.3% and specificity of 99.8% and hence can be taken as a cut off value for the diagnosis of pleural TB based on receiver-operating characteristic analysis. Conclusion: TB contributed to 60% of undiagnosed exudative pleural effusions in the present study. MT had 100% yield in the diagnosis of undiagnosed exudative effusions. Pleural fluid ADA levels may help in differentiating TB versus malignant effusion.

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.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.One hundred and twenty-seven PE patients were enrolled in the study and then were divided into pleural TB (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.

OBJECTIVE: To establish the diagnostic nomogram for tuberculous pleurisy (TP) based on TB-interferon-gamma release assays (TB-IGRA), as well as clinical and peripheral blood characteristics.MATERIAL AND METHODS: Patients who underwent TB-IGRA tests during hospitalisation and were finally diagnosed, were retrospectively and continuously enrolled. TP was divided into confirmed TP (cTP) and presumptive TP (pTP), and corresponding diagnostic nomograms were established.RESULTS: A total of 1283 patients were enrolled (median age 49 years, range 14–96; males: 63.1%). The area under the curve (AUC) of TB-IGRA was 0.81 (95%CI 0.77–0.84) for cTP (n = 272) and 0.74 (95%CI 0.71–0.78) for pTP (n = 644). The false-positive and negative rates of TB-IGRA among non-TP and cTP were respectively 32.4% and 16.8%. Based on LASSO analysis, we then selected respectively 12 and 10 predictors from clinical and peripheral blood characteristics to establish cTP and pTP nomograms (TB-IGRA was selected). The cTP and pTP nomograms had an AUC of 0.93 (95%CI 0.90–0.95) and 0.92 (95%CI 0.90–0.94) in the training group, and 0.91 (95%CI 0.87–0.96) and 0.93 (95%CI 0.89–0.96) in the validation group, respectively, which were superior to TB-IGRA test alone.CONCLUSION: Novel predictive nomograms with less invasiveness were provided based on TB-IGRA test to assist differential diagnosis of TP and non-TP patients.