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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">ETM</journal-id>
<journal-title-group>
<journal-title>Experimental and Therapeutic Medicine</journal-title>
</journal-title-group>
<issn pub-type="ppub">1792-0981</issn>
<issn pub-type="epub">1792-1015</issn>
<publisher>
<publisher-name>D.A. Spandidos</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="publisher-id">ETM-29-4-12837</article-id>
<article-id pub-id-type="doi">10.3892/etm.2025.12837</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Articles</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Value of ultrasound‑guided puncture combined with GeneXpert MTB/RIF technology in the diagnosis of pleural tuberculosis</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name><surname>Qin</surname><given-names>Yi</given-names></name>
<xref rid="af1-ETM-29-4-12837" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Jia</surname><given-names>Shouqin</given-names></name>
<xref rid="af2-ETM-29-4-12837" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Cui</surname><given-names>Jia</given-names></name>
<xref rid="af3-ETM-29-4-12837" ref-type="aff">3</xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Yan</surname><given-names>Qingmei</given-names></name>
<xref rid="af4-ETM-29-4-12837" ref-type="aff">4</xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Xue</surname><given-names>Feng</given-names></name>
<xref rid="af5-ETM-29-4-12837" ref-type="aff">5</xref>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name><surname>Yan</surname><given-names>Qinghu</given-names></name>
<xref rid="af3-ETM-29-4-12837" ref-type="aff">3</xref>
<xref rid="c1-ETM-29-4-12837" ref-type="corresp"/>
</contrib>
</contrib-group>
<aff id="af1-ETM-29-4-12837"><label>1</label>Department of Medicine, Shandong Public Health Clinical Center, Shandong University, Jinan, Shandong 250013, P.R. China</aff>
<aff id="af2-ETM-29-4-12837"><label>2</label>Department of Radiology, Shandong Public Health Clinical Center, Shandong University, Jinan, Shandong 250013, P.R. China</aff>
<aff id="af3-ETM-29-4-12837"><label>3</label>Department of Ultrasound, Shandong Public Health Clinical Center, Shandong University, Jinan, Shandong 250013, P.R. China</aff>
<aff id="af4-ETM-29-4-12837"><label>4</label>Department of Emergency, Shizhong District People&#x0027;s Hospital, Jinan, Shandong 250000, P.R. China</aff>
<aff id="af5-ETM-29-4-12837"><label>5</label>Department of Radiology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China</aff>
<author-notes>
<corresp id="c1-ETM-29-4-12837"><italic>Correspondence to:</italic> Dr Qinghu Yan, Department of Ultrasound, Shandong Public Health Clinical Center, 46 Lishan Road, Lixia, Jinan, Shandong 250013, P.R. China <email>545088301@qq.com </email></corresp>
<fn><p><italic>Abbreviations:</italic> TB, tuberculosis; WHO, World Health Organization; ROC, receiver operating characteristic curve; CRS, Common Reporting Standard; AUC, area under curve</p></fn>
</author-notes>
<pub-date pub-type="collection">
<month>04</month>
<year>2025</year></pub-date>
<pub-date pub-type="epub">
<day>04</day>
<month>03</month>
<year>2025</year></pub-date>
<volume>29</volume>
<issue>4</issue>
<elocation-id>87</elocation-id>
<history>
<date date-type="received">
<day>25</day>
<month>04</month>
<year>2024</year>
</date>
<date date-type="accepted">
<day>03</day>
<month>01</month>
<year>2025</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright: &#x00A9; 2025 Qin et al.</copyright-statement>
<copyright-year>2025</copyright-year>
<license license-type="open-access">
<license-p>This is an open access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by-nc-nd/4.0/">Creative Commons Attribution-NonCommercial-NoDerivs License</ext-link>, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.</license-p></license>
</permissions>
<abstract>
<p>The aim of the present study was to analyze the pathological and laboratory findings of pleural lesions post ultrasound-guided biopsy and to assess the diagnostic utility of percutaneous ultrasound-guided puncture combined with GeneXpert <italic>Mycobacterium tuberculosis</italic> (MTB)/resistance to rifampin (RIF) in pleural tuberculosis (TB) diagnosis. A retrospective analysis was conducted on 46 patients who underwent ultrasound-guided biopsy at the Shandong Public Health Clinical Center (Shandong Chest Hospital) between April 2018 and April 2021. Of these, 27 patients were diagnosed with pleural TB, while 19 were confirmed to have non-pleural TB. Preoperative examinations were negative for all patients. Under ultrasound guidance, tissue samples were obtained through puncture for subsequent pathological and laboratory examination. All collected samples were subjected to acid fast staining, <italic>M. tuberculosis</italic> culture and GeneXpert MTB/RIF (Cepheid). The sensitivity, specificity and area under curve (AUC) value were compared across methods. Rifampicin drug susceptibility was detected using the proportional method and compared with results obtained from GeneXpert MTB/RIF. The sensitivity and specificity of acid-fast staining, <italic>M. tuberculosis</italic> culture and GeneXpert MTB/RIF in diagnosing pleural TB were 18.52 and 100.00&#x0025;, 14.81 and 100.00, 96.30 and 94.74&#x0025;, respectively. Consistency analysis demonstrated that the GeneXpert MTB/RIF technique exhibited good agreement (&#x03BA;=0.91), whereas the agreement for acid fast staining (&#x03BA;=0.16) and <italic>M. tuberculosis</italic> culture (&#x03BA;=0.13) was poor. Data analysis was performed by combining the results of the three detection methods with pathological findings. The diagnostic value for pleural TB was highest for GeneXpert MTB/RIF technology combined with pathology (AUC value=0.97), followed by <italic>M. tuberculosis</italic> culture combined with pathology (AUC value=0.94) and acid-fast staining combined with pathology (AUC value=0.94). No surgical complications were observed. Of the 27 samples, 4 tested positive using the <italic>M. tuberculosis</italic> culture method. Rifampicin resistance was detected from the bacterial colonies through the proportional method, with results consistent with those obtained from the GeneXpert MTB/RIF method. Ultrasound-guided percutaneous biopsy is considered a safe and effective approach for diagnosing pleural TB, Its sensitivity is much higher than that of pleural effusion, Moreover, there is currently limited research on ultrasound-guided pleural biopsy combined with laboratory testing worldwide. Ultrasound-guided puncture combined with GeneXpert MTB/RIF technology is of significant value in the diagnosis of pleural TB and in determining rifampicin resistance.</p>
</abstract>
<kwd-group>
<kwd>tuberculosis</kwd>
<kwd>puncture biopsy</kwd>
<kwd>ultrasound guidance</kwd>
<kwd>pleural tuberculosis</kwd>
<kwd>GeneXpert MTB/RIF</kwd>
</kwd-group>
<funding-group>
<funding-statement><bold>Funding:</bold> The present study was funded by the Shandong medical and health science and technology development plan project (grant no. 202309020993).</funding-statement>
</funding-group>
</article-meta>
</front>
<body>
<sec sec-type="intro">
<title>Introduction</title>
<p>Tuberculosis (TB) is an infectious disease caused by <italic>Mycobacterium tuberculosis</italic>. According to World Health Organization (WHO), TB ranks among the 10 leading causes of death globally and is the leading cause of mortality from a single infectious agent (<xref rid="b1-ETM-29-4-12837" ref-type="bibr">1</xref>). While pulmonary tuberculosis is the most common manifestation, global statistics from 2019 indicate that &#x007E;16&#x0025; of global tuberculosis cases were extrapulmonary (<xref rid="b1-ETM-29-4-12837" ref-type="bibr">1</xref>). Extrapulmonary tuberculosis can affect nearly any organ, most frequently involving the lymph nodes, followed by pleural TB (<xref rid="b2-ETM-29-4-12837" ref-type="bibr">2</xref>). Studies have demonstrated that the proportion of extrapulmonary tuberculosis cases among total tuberculosis cases has been gradually increasing (<xref rid="b3-ETM-29-4-12837" ref-type="bibr">3</xref>,<xref rid="b4-ETM-29-4-12837" ref-type="bibr">4</xref>). Pleural TB is prone to misdiagnosis due to its atypical clinical symptoms, lack of characteristic imaging manifestations, challenges in specimen acquisition, low etiology positivity rate, and difficulties in diagnosis. In a number of cases, confirmation is required through biopsy. Ultrasound offers portability and high resolution and ultrasound-guided puncture biopsy provides real-time imaging, safety and ease of operation. It is an effective method for diagnosing pleural TB and is crucial for differentiating pleural TB from other infectious and non-infectious diseases (<xref rid="b5-ETM-29-4-12837" ref-type="bibr">5</xref>). Conventional methods for detecting tuberculosis include smear microscopy, culture and cytology; however, these methods possess certain limitations. Mycobacterial culture can serve as a reference standard but is time-consuming and requires skilled personnel for operation. Cytological methods for detecting lymphadenopathy necessitate expert interpretation and smaller laboratories often lack the necessary equipment, such as &#xFB02;uorescence or LED microscopes. These factors hinder the accurate and prompt diagnosis of patients with lymphatic tuberculosis in low-resource settings (<xref rid="b6-ETM-29-4-12837" ref-type="bibr">6</xref>). Real-time fluorescence quantitative nucleic acid amplification using GeneXpert <italic>M. tuberculosis</italic> (MTB)/resistance to rifampin (RIF), a novel diagnostic technology for tuberculosis (<xref rid="b6-ETM-29-4-12837" ref-type="bibr">6</xref>), can detect <italic>M. tuberculosis</italic> complex DNA. This method allows for the detection of rifampicin resistance-related mutations in the rpoB gene during the identification of <italic>M. tuberculosis</italic> complex, facilitating early and rapid diagnosis while effectively minimizing the risk of cross-contamination. Additionally, GeneXpert MTB/RIF (Cepheid) is less influenced by the presence of anti-tuberculosis drugs (<xref rid="b6-ETM-29-4-12837" ref-type="bibr">6</xref>). Additionally, enhanced sensitivity, specificity and accuracy in detecting rifampicin resistance are notable advantages of this method. The present study aimed to investigate the value of ultrasound-guided pleural TB puncture combined with GeneXpert MTB/RIF in diagnosing pleural TB. However, among all the searches, there is only one study that confirms the diagnosis of pleural TB by ultrasound-guided pleural biopsy combined with GeneXpert MTB/RIF, indicating that this is still not widely promoted or used and has not been recognized by clinical doctors. The present study also aimed to further confirm the diagnostic value and significance of this study for pleural TB (<xref rid="b7-ETM-29-4-12837" ref-type="bibr">7</xref>).</p>
</sec>
<sec sec-type="Materials|methods">
<title>Materials and methods</title>
<sec>
<title/>
<sec>
<title>Patients</title>
<p>The pathology, acid fast staining, <italic>Mycobacterium</italic> culture and GeneXpert results of patients with pleural lesions who underwent ultrasound-guided biopsy between April 2018 and April 2021 at the Shandong Public Health Clinical Center (Shandong Chest Hospital) were retrospectively analyzed. Diagnosis of tuberculosis was conducted following the guidelines set forth by the WHO (<xref rid="b1-ETM-29-4-12837" ref-type="bibr">1</xref>) and the clinical diagnostic standards established by the Chinese Medical Association for tuberculosis (<xref rid="b8-ETM-29-4-12837" ref-type="bibr">8</xref>). Clinically diagnosed TB patients met the following criteria: i) Presence of clinical symptoms consistent with tuberculosis; ii) imaging highly suggestive of tuberculosis; and iii) satisfactory response to anti-tuberculosis treatment (<xref rid="b9-ETM-29-4-12837" ref-type="bibr">9</xref>). All lesions were routinely examined by ultrasound prior to biopsy. Clinical case data were collected, including patient age, sex, comorbidities, laboratory examination results and treatment response. None of the patients received treatment before biopsy. A flow diagram illustrating the study process is provided (<xref rid="f1-ETM-29-4-12837" ref-type="fig">Fig. 1</xref>). The patients with TB included 19 males and 8 females, with ages ranging from 16-56 years and a mean age of 23.7&#x00B1;14.1 years. Pulmonary tuberculosis was present as a complication in 17 cases.</p>
<p>All methods were carried out in accordance with relevant guidelines and regulations. The present study protocols were approved by the Ethics Committee of Shandong Public Health Clinical Center (Shandong Chest Hospital; approval no. 2021XKYYEC-33).</p>
</sec>
<sec>
<title>Ultrasound puncture</title>
<p>Based on the location of pleural lesions, patients were positioned differently, including sitting, supine, lateral or prone. The optimal puncture pathway for accessing pleural lesions was determined. This pathway was designed to avoid the ribs and to run obliquely at a shallow angle to the pleural plane, thereby facilitating the visualization of the puncture needle, enabling the acquisition of a greater volume of pleural tissue, and minimizing the risk of lung tissue puncture. Color Doppler flow imaging was employed to assess the blood supply to the lesion, ensuring that large blood vessels along the puncture pathway were avoided and that the pleural tissue with blood supply was targeted. The needle entry point was identified and marked accordingly. Routine disinfection was performed and a sterile towel was placed over the area. Local infiltration anesthesia was administered. An ultrasonic diagnostic instrument (Philips Q5; Philips Healthcare) equipped with a convex array probe (C5-1) operating at a frequency of 1 to 5 MHz was used. Puncture was carried out according to the predetermined pathway using a No. 18 semi-automatic cutting biopsy needle (18G; 10 cm; Becton, Dickinson and Company). The needle was inserted under real-time ultrasound guidance (<xref rid="f2-ETM-29-4-12837" ref-type="fig">Fig. 2A</xref> and <xref rid="f2-ETM-29-4-12837" ref-type="fig">B</xref>). Once the needle tip was observed to reach the target area, the biopsy gun was activated to obtain a tissue sample. Depending on the specimen condition, tissue acquisition was performed 2-3 times. The changes in chest pain, dizziness and chest tightness were monitored during the procedure. Postoperatively, ultrasonography was conducted to assess for complications such as hemoptysis, pneumothorax and bleeding. Pathological examination, acid fast staining, <italic>M. tuberculosis</italic> culture and GeneXpert testing were performed in all cases. Specimens were fixed in 10&#x0025; formalin solution for 18-24 h at 20-35&#x02DA;C and subsequently submitted for pathological analysis.</p>
</sec>
<sec>
<title>Histopathological examination</title>
<p>The specimens were dehydrated using a gradient of ethanol from low to high concentration and embedded in high concentration paraffin. Subsequently, they were sectioned at 15-30 &#x00B5;m. A 4 &#x00B5;m color band was prepared for staining (<xref rid="f3-ETM-29-4-12837" ref-type="fig">Fig. 3A</xref> and <xref rid="f3-ETM-29-4-12837" ref-type="fig">B</xref>), followed by pathological diagnosis.</p>
<p>Acid fast staining was performed using an acid fast staining solution (Zhuhai Beso Biotechnology Co., Ltd.), experienced laboratory doctors applied the modified alkaline reddening method to conduct the procedure. The staining temperature was 60&#x02DA;C for 5 min. The results were determined according to the reagent instructions.</p>
<p><italic>M. tuberculosis</italic> culture was carried out using the <italic>Mycobacterium</italic> culture monitoring system and reagents provided by BACTEC MGIT 960 (Becton, Dickinson and Company) for strain identification, following the manufacturer&#x0027;s instructions and specifications. GeneXpert MTB/RIF detection was performed using the GeneXpert MTB/RIF and an automated detection platform &#x005B;GeneXpert (Cepheid)&#x005D;. Samples were pretreated according to the operating procedures, and automatic detection and result interpretation were conducted as per the guidelines.</p>
</sec>
<sec>
<title>Statistical analysis</title>
<p>The database was established and statistically analyzed using SPSS 24.0 (IBM Corp.). Indicators for statistical description include mean, standard deviation, frequency and composition ratio. Data following a normal distribution were expressed as mean and standard deviation, while non-normally distributed data were reported as median and interquartile range (m&#x00B1;IQR). Statistical inference was conducted using ROC curve analysis, &#x03BA;-value, sensitivity, specificity, positive predictive value and negative predictive value. P&#x003C;0.05 was considered to indicate a statistically significant difference. The optimal diagnostic threshold was determined using the Jordan index (<xref rid="f4-ETM-29-4-12837" ref-type="fig">Fig. 4</xref>).</p>
</sec>
</sec>
</sec>
<sec sec-type="Results">
<title>Results</title>
<p>Using Common Reporting Standard (CRS) as a reference, 27 patients were diagnosed with tuberculous nodal pleurisy (<xref rid="f1-ETM-29-4-12837" ref-type="fig">Fig. 1</xref>), including 19 males and eight females, with ages ranging from 16-56 years and a mean age of 23.7&#x00B1;14.1 years. Pulmonary tuberculosis was present as a complication in 17 cases.</p>
<sec>
<title/>
<sec>
<title>Pathological results</title>
<p>Ultrasound-guided pleural biopsy was conducted based on the microscopic observation of fibrous tissue or mesothelial cells. Pleural tissue was successfully obtained from all 46 patients, with a success rate of 100&#x0025; (46/46). The length of the puncture tissue strips ranged from 0.5-1.8 cm. Pathological diagnosis revealed malignancy in seven cases, tuberculosis in 24 cases and chronic inflammation in 15 cases. Among the 15 cases of chronic pleural inflammation, three were ultimately diagnosed as tuberculous pleurisy. The pathological diagnosis of malignancy was consistent with the final clinical diagnosis, accounting for 15.21&#x0025; (7/46) of all biopsies. Using CRS as a reference, 27 patients were ultimately diagnosed with tuberculous pleurisy, based on clinical manifestations, imaging examination and diagnostic treatment results.</p>
</sec>
<sec>
<title>Laboratory results</title>
<p>Among the 27 patients with pleural TB, <italic>M. tuberculosis</italic> culture was positive in four cases, acid-fast staining (<xref rid="f3-ETM-29-4-12837" ref-type="fig">Fig. 3A</xref> and <xref rid="f3-ETM-29-4-12837" ref-type="fig">B</xref>) was positive in 5 cases, and GeneXpert MTB/RIF was positive in 26 cases (<xref rid="tI-ETM-29-4-12837" ref-type="table">Table I</xref>). The positive diagnostic rates for <italic>M. tuberculosis</italic> culture, acid-fast staining and GeneXpert MTB/RIF were 14.81, 18.52 and 96.30&#x0025;, respectively. Among the 27 confirmed cases of pleural TB, GeneXpert MTB/RIF exhibited the highest positive rate, with the combination of GeneXpert MTB/RIF and pathology yielding a positive rate of 100&#x0025;. GeneXpert MTB/RIF was positive in all four culture-positive cases. In 15 cases where <italic>M. tuberculosis</italic> culture and acid-fast staining were negative and GeneXpert MTB/RIF was positive. Finally, chest wall tuberculosis was ultimately diagnosed. GeneXpert MTB/RIF increased the pathogenic-positive detection rate of tissue biopsy specimens by 55.56&#x0025; (15/27). The &#x03BA;-value for GeneXpert MTB/RIF technology as shown in <xref rid="tII-ETM-29-4-12837" ref-type="table">Table II</xref> was 0.91; the &#x03BA;-values for acid-fast staining and <italic>M. tuberculosis</italic> culture were 0.16 and 0.13, respectively. The AUC value for GeneXpert MTB/RIF technology was 0.96, while the AUC values for acid-fast staining and <italic>M. tuberculosis</italic> culture were 0.59 and 0.57, respectively. The positive diagnostic rate, AUC and &#x03BA;-values for the combination of pathology and GeneXpert MTB/RIF were 100.00&#x0025;, 0.94 and 0.92, respectively, all of which were higher than those for the combination of pathology with acid-fast staining or <italic>Mycobacterium tuberculosis</italic> culture.</p>
</sec>
<sec>
<title>Complications of ultrasound-guided puncture</title>
<p>None of the 46 patients experienced complications such as hemoptysis, pneumothorax and hemothorax; Only one patient presented with a pleural reaction characterized by dizziness and nausea, with an incidence rate of 1&#x0025; (1/46). After bed rest, the symptoms resolved and the puncture was successfully repeated, allowing the procedure to be completed without further issues.</p>
</sec>
</sec>
</sec>
<sec sec-type="Discussion">
<title>Discussion</title>
<p>Pleurisy is a common clinical condition, and tuberculous pleurisy is a form caused by <italic>M. tuberculosis</italic> infection. The underlying mechanism involves the entry of <italic>M. tuberculosis</italic> and tuberculous proteins into the pleural space, triggering a significant pleural reaction, primarily characterized by pleural effusion and pleural thickening (<xref rid="b9-ETM-29-4-12837" ref-type="bibr">9</xref>). The clinical symptoms of tuberculous pleurisy are nonspecific, making diagnosis challenging. Routine diagnostic methods often fail to achieve definitive results. Imaging examinations play a crucial role in detecting pleural lesions, however, diagnosis requires pathological and laboratory confirmation. According to the 2010 guidelines of the British Thoracic Society for the diagnosis and management of unilateral pleural effusion in adults, when the nature of pleural effusion cannot be determined through ultrasound-guided aspiration, it is recommended that pleural biopsy be performed under imaging guidance to further clarify the nature of the lesion (<xref rid="b10-ETM-29-4-12837" ref-type="bibr">10</xref>). Historically, Cope biopsy needles and Abrams biopsy needles were used for percutaneous pleural biopsy; however, these methods provided limited tissue samples and were associated with significant trauma, making complications such as pneumothorax and bleeding more likely (<xref rid="b11-ETM-29-4-12837" ref-type="bibr">11</xref>,<xref rid="b12-ETM-29-4-12837" ref-type="bibr">12</xref>). Defrancis <italic>et al</italic> (<xref rid="b13-ETM-29-4-12837" ref-type="bibr">13</xref>) first introduced closed pleural biopsy into clinical practice, and through continuous refinement, it has become a primary diagnostic method for pleural lesions. Nevertheless, variations in guiding techniques have led to differences in the sensitivity and specificity for diagnosing pleural diseases (<xref rid="b13-ETM-29-4-12837" ref-type="bibr">13</xref>). Thoracoscopic biopsy has been shown to enhance the diagnostic accuracy of GeneXpert MTB/RIF for tuberculosis (<xref rid="b14-ETM-29-4-12837" ref-type="bibr">14</xref>), but the procedure is associated with greater trauma and carries a risk of postoperative infection and tuberculosis transmission. Ultrasound-guided biopsy, characterized by high precision, minimal invasiveness and safety, allows for accurate specimen collection, facilitating both pathological and laboratory examinations.</p>
<p>Pleural TB has been recognized for a long time. When the duration of tuberculous pleurisy exceeds 4 weeks, the positive rate of pleural biopsy is markedly reduced (<xref rid="b15-ETM-29-4-12837" ref-type="bibr">15</xref>). Most cases of pleural TB involve paucibacillary disease (caused by a small number of bacteria), which reduces the sensitivity of traditional smear microscopy for diagnosis. In resource-limited settings, <italic>Mycobacterium</italic> culture and histological examination are not widely available due to the long culture time and the need for fully equipped laboratories. GeneXpert MTB/RIF is an automated PCR test capable of accurately detecting tuberculosis and rifampicin resistance in sputum samples (<xref rid="b16-ETM-29-4-12837" ref-type="bibr">16</xref>). Based on a systematic review (<xref rid="b17-ETM-29-4-12837" ref-type="bibr">17</xref>), the World Health Organization issued recommendations regarding extrapulmonary tuberculosis, stating that GeneXpert MTB/RIF can be used as an alternative to conventional methods (such as routine microscopy, culture or histopathology) to detect specific non-respiratory specimens from patients with suspected extrapulmonary tuberculosis.</p>
<p>GeneXpert MTB/RIF is a diagnostic test used for detecting the DNA of the <italic>M. tuberculosis</italic> complex. Upon identification of the <italic>M. tuberculosis</italic> complex, mutations related to rifampicin resistance in the rpoB gene are detected. Test results can be obtained within 2 h after the initiation of the test, requiring only minimal technical time. Unlike traditional nucleic acid amplification tests, GeneXpert MTB/RIF integrates sample processing, PCR amplification and detection into a single self-contained test unit (<xref rid="b18-ETM-29-4-12837" ref-type="bibr">18</xref>). Following sample loading, all analytical steps are all fully automated and self-sufficient. GeneXpert MTB/RIF employs molecular beacon technology to detect rifampicin resistance. Molecular beacons are nucleic acid probes that can identify and report the presence or absence of normal, favorable and wild type sequences of the rpoB gene.</p>
<p>In the present study, the positive rate of GeneXpert MTB/RIF combined with pathology was found to be 100&#x0025;, while the positive rate of GeneXpert MTB/RIF alone was 96.30&#x0025; (26/27), both of which were higher than the rates observed for acid-fast staining and tuberculous culture. The three detection methods were analyzed in conjunction with pathology for data evaluation. The diagnostic value for pleural TB was determined to be as follows: GeneXpert MTB/RIF technology combined with pathology (AUC value=0.97) &#x003E; tuberculosis culture combined with pathology (AUC value=0.94)=acid-fast staining combined with pathology (AUC value=0.94). The positive rate of GeneXpert MTB/RIF in the present study was higher than that reported in previous studies involving ultrasound-guided or closed pleural biopsy (<xref rid="b19-ETM-29-4-12837" ref-type="bibr">19</xref>).</p>
<p>Some researchers consider the clinical diagnosis of tuberculous pleurisy and tuberculous pericarditis to be the gold standard. GeneXpert MTB/RIF demonstrates high sensitivity (90.0 and 72.0&#x0025;) and specificity (100.0&#x0025; for both) (<xref rid="b20-ETM-29-4-12837" ref-type="bibr">20</xref>), which is consistent with the findings of the present study. Additionally, research has been conducted regarding the value of GeneXpert MTB/RIF in detecting drug-resistant tuberculous pleurisy. Among 60 patients with tuberculous pleurisy, GeneXpert MTB/RIF confirmed the presence of rifampicin resistance genes in 10 cases, while only five cases were identified using the proportional method (<xref rid="b21-ETM-29-4-12837" ref-type="bibr">21</xref>).</p>
<p>In the present study, four cases tested positive using the <italic>M. tuberculosis</italic> culture method. The colonies were evaluated using the proportional method, and the results were consistent with those obtained from the GeneXpert MTB/RIF method. A limitation of this study may be attributed to the small volume of positive tuberculosis culture data included. Numerous studies have demonstrated that GeneXpert MTB/RIF is highly valuable for diagnosing extrapulmonary tuberculosis, including lymphatic tuberculosis, spinal tuberculosis, urinary tuberculosis and nervous system tuberculosis (<xref rid="b22-ETM-29-4-12837 b23-ETM-29-4-12837 b24-ETM-29-4-12837 b25-ETM-29-4-12837" ref-type="bibr">22-25</xref>). Additionally, there are studies confirming its diagnostic value in pleural TB (<xref rid="b26-ETM-29-4-12837" ref-type="bibr">26</xref>). The findings of the present study align with these previous results. The positive rate of GeneXpert MTB/RIF, along with its AUC and &#x03BA;-values were higher than those of acid-fast staining and tuberculosis culture. Furthermore, in the analysis of all combined experiments, the positive rate, AUC and &#x03BA;-values for GeneXpert MTB/RIF combined with pathology were also the highest.</p>
<p>The consistency analysis indicated that GeneXpert MTB/RIF technology demonstrated good consistency (&#x03BA;=0.91), whereas acid-fast staining (&#x03BA;=0.16) and tuberculosis culture (&#x03BA;=0.13) exhibit poor consistency. This may be attributed to the limited number of cases included. Although GeneXpert MTB/RIF facilitates the detection of <italic>M. tuberculosis</italic> and rifampicin resistance, it cannot fully replace traditional methods for assessing rifampicin resistance. The total number of cases included in the present study was not particularly large. The diagnosis of tuberculosis relies not only on pathological findings but also on etiological assessments. Most patients included in the present study were clinically suspected of having tuberculosis, resulting in a specificity of 100&#x0025;, which is consistent with numerous research findings and does not impact the generalizability of the results.</p>
<p>In conclusion ultrasound-guided percutaneous biopsy, in conjunction with laboratory examination, is recognized as a safe and effective method for diagnosing pleural TB. The combination of ultrasound-guided puncture and GeneXpert MTB/RIF exhibits high sensitivity and specificity, demonstrating significant value in the diagnosis of pleural TB and the detection of rifampicin resistance.</p>
</sec>
</body>
<back>
<ack>
<title>Acknowledgements</title>
<p>Not applicable.</p>
</ack>
<sec sec-type="data-availability">
<title>Availability of data and materials</title>
<p>The data generated in the present study may be requested from the corresponding author.</p>
</sec>
<sec>
<title>Authors&#x0027; contributions</title>
<p>QY and YQ made substantial contributions to conception and design. QY and JC made substantial contributions to acquisition of data. FX, JC and SJ made substantial contributions to analysis and interpretation of data. YQ and QY wrote the manuscript. QY and FX constructed figures. JC and QY constructed the tables. YQ and SJ confirm the authenticity of all the raw data. All authors have read and approved the final manuscript.</p>
</sec>
<sec>
<title>Ethics approval and consent to participate</title>
<p>The present study met the conditions of the Helsinki declaration. All methods were carried out in accordance with relevant guidelines and regulations and all experimental protocols were approved by the Ethics Committee of Shandong Public Health Clinical Center (Shandong Chest Hospital; approval no. 2021XKYYEC-33). Informed consent was waived by the Ethics Committee of Shandong Public Health Clinical Center (Shandong Chest Hospital)/2021XKYYEC-33 for this study due to retrospective nature.</p>
</sec>
<sec>
<title>Patient consent for publication</title>
<p>Not applicable.</p>
</sec>
<sec sec-type="COI-statement">
<title>Competing interests</title>
<p>The authors declare that they have no competing interests.</p>
</sec>
<ref-list>
<title>References</title>
<ref id="b1-ETM-29-4-12837"><label>1</label><element-citation publication-type="journal"><comment>World Health Organization. Global tuberculosis report 2020. Geneva, World Health Organization, 2020.</comment></element-citation></ref>
<ref id="b2-ETM-29-4-12837"><label>2</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Peto</surname><given-names>HM</given-names></name><name><surname>Pratt</surname><given-names>RH</given-names></name><name><surname>Harrington</surname><given-names>TA</given-names></name><name><surname>LoBue</surname><given-names>PA</given-names></name><name><surname>Armstrong</surname><given-names>LR</given-names></name></person-group><article-title>Epidemiology of extrapulmonary tuberculosis in the United States, 1993-2006</article-title><source>Clin Infect Dis</source><volume>49</volume><fpage>1350</fpage><lpage>1357</lpage><year>2009</year><pub-id pub-id-type="pmid">19793000</pub-id><pub-id pub-id-type="doi">10.1086/605559</pub-id></element-citation></ref>
<ref id="b3-ETM-29-4-12837"><label>3</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sandgren</surname><given-names>A</given-names></name><name><surname>Hollo</surname><given-names>V</given-names></name><name><surname>van der Werf</surname><given-names>MJ</given-names></name></person-group><article-title>Extrapulmonary tuberculosis in the European Union and European Economic Area, 2002 to 2011</article-title><source>Euro Surveill</source><volume>18</volume><issue>20431</issue><year>2013</year><pub-id pub-id-type="pmid">23557943</pub-id></element-citation></ref>
<ref id="b4-ETM-29-4-12837"><label>4</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>X</given-names></name><name><surname>Yang</surname><given-names>Z</given-names></name><name><surname>Fu</surname><given-names>Y</given-names></name><name><surname>Zhang</surname><given-names>G</given-names></name><name><surname>Wang</surname><given-names>X</given-names></name><name><surname>Zhang</surname><given-names>Y</given-names></name><name><surname>Wang</surname><given-names>X</given-names></name></person-group><article-title>Insight to the epidemiology and risk factors of extrapulmonary tuberculosis in Tianjin, China during 2006-2011</article-title><source>PLoS One</source><volume>9</volume><issue>e112213</issue><year>2014</year><pub-id pub-id-type="pmid">25494360</pub-id><pub-id pub-id-type="doi">10.1371/journal.pone.0112213</pub-id></element-citation></ref>
<ref id="b5-ETM-29-4-12837"><label>5</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nachiappan</surname><given-names>AC</given-names></name><name><surname>Rahbar</surname><given-names>K</given-names></name><name><surname>Shi</surname><given-names>X</given-names></name><name><surname>Guy</surname><given-names>ES</given-names></name><name><surname>Mortani Barbosa</surname><given-names>EJ Jr</given-names></name><name><surname>Shroff</surname><given-names>GS</given-names></name><name><surname>Ocazionez</surname><given-names>D</given-names></name><name><surname>Schlesinger</surname><given-names>AE</given-names></name><name><surname>Katz</surname><given-names>SI</given-names></name><name><surname>Hammer</surname><given-names>MM</given-names></name></person-group><article-title>Pulmonary tuberculosis: Role of radiology in diagnosis and management</article-title><source>Radiographics</source><volume>37</volume><fpage>52</fpage><lpage>72</lpage><year>2017</year><pub-id pub-id-type="pmid">28076011</pub-id><pub-id pub-id-type="doi">10.1148/rg.2017160032</pub-id></element-citation></ref>
<ref id="b6-ETM-29-4-12837"><label>6</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bholla</surname><given-names>M</given-names></name><name><surname>Kapalata</surname><given-names>N</given-names></name><name><surname>Masika</surname><given-names>E</given-names></name><name><surname>Chande</surname><given-names>H</given-names></name><name><surname>Jugheli</surname><given-names>L</given-names></name><name><surname>Sasamalo</surname><given-names>M</given-names></name><name><surname>Glass</surname><given-names>TR</given-names></name><name><surname>Beck</surname><given-names>HP</given-names></name><name><surname>Reither</surname><given-names>K</given-names></name></person-group><article-title>Evaluation of Xpert<sup>&#x00AE;</sup> MTB/RIF and Ustar EasyNAT&#x2122; TB IAD for diagnosis of tuberculous lymphadenitis of children in Tanzania: A prospective descriptive study</article-title><source>BMC Infect Dis</source><volume>16</volume><issue>246</issue><year>2016</year><pub-id pub-id-type="pmid">27268404</pub-id><pub-id pub-id-type="doi">10.1186/s12879-016-1578-z</pub-id></element-citation></ref>
<ref id="b7-ETM-29-4-12837"><label>7</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sun</surname><given-names>W</given-names></name><name><surname>Zhou</surname><given-names>Y</given-names></name><name><surname>Li</surname><given-names>W</given-names></name><name><surname>Wang</surname><given-names>Y</given-names></name><name><surname>Xiong</surname><given-names>K</given-names></name><name><surname>Zhang</surname><given-names>Z</given-names></name><name><surname>Fan</surname><given-names>L</given-names></name></person-group><article-title>Diagnostic yield of Xpert MTB/RIF on contrast-enhanced ultrasound-guided pleural biopsy specimens for pleural tuberculosis</article-title><source>Intl J Infect Dis</source><volume>108</volume><fpage>89</fpage><lpage>95</lpage><year>2021</year><pub-id pub-id-type="pmid">33992762</pub-id><pub-id pub-id-type="doi">10.1016/j.ijid.2021.05.023</pub-id></element-citation></ref>
<ref id="b8-ETM-29-4-12837"><label>8</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rice</surname><given-names>JP</given-names></name><name><surname>Seifert</surname><given-names>M</given-names></name><name><surname>Moser</surname><given-names>KS</given-names></name><name><surname>Rodwell</surname><given-names>TC</given-names></name></person-group><article-title>Performance of the Xpert MTB/RIF assay for the diagnosis of pulmonary tuberculosis and rifampin resistance in a low-incidence, high-resource setting</article-title><source>PLoS One</source><volume>12</volume><issue>e0186139</issue><year>2017</year><pub-id pub-id-type="pmid">29016684</pub-id><pub-id pub-id-type="doi">10.1371/journal.pone.0186139</pub-id></element-citation></ref>
<ref id="b9-ETM-29-4-12837"><label>9</label><element-citation publication-type="journal"><comment>Chinese Medical Association. Clinical diagnosis standardof TB for clinicaltechnologyoperation(TBvol-umes). People&#x0027;s Medical Publishing House, 2005.</comment></element-citation></ref>
<ref id="b10-ETM-29-4-12837"><label>10</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jian</surname><given-names>S</given-names></name><name><surname>Rong</surname><given-names>ZL</given-names></name><name><surname>Baohua</surname><given-names>S</given-names></name></person-group><article-title>Diagnostic value of pleural histopathology and pleural effusion in tuberculous pleurisy</article-title><source>Western Med</source><volume>27</volume><fpage>27</fpage><lpage>28</lpage><year>2015</year></element-citation></ref>
<ref id="b11-ETM-29-4-12837"><label>11</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hooper</surname><given-names>C</given-names></name><name><surname>Lee</surname><given-names>YC</given-names></name><name><surname>Maskell</surname><given-names>N</given-names></name></person-group><comment>BTS Pleural Guideline Group</comment><article-title>Investigation of a unilateral pleural effusion in adults: British Thoracic Society pleural disease guideline 2010</article-title><source>Thorax</source><volume>65</volume><fpage>4</fpage><lpage>17</lpage><year>2010</year><pub-id pub-id-type="pmid">20696692</pub-id><pub-id pub-id-type="doi">10.1136/thx.2010.136978</pub-id></element-citation></ref>
<ref id="b12-ETM-29-4-12837"><label>12</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Barnes</surname><given-names>TW</given-names></name><name><surname>Morgenthaler</surname><given-names>TI</given-names></name><name><surname>Olson</surname><given-names>EJ</given-names></name><name><surname>Hesley</surname><given-names>GK</given-names></name><name><surname>Decker</surname><given-names>PA</given-names></name><name><surname>Ryu</surname><given-names>JH</given-names></name></person-group><article-title>Sonographically guided thoracentesis and rate of pneumothorax</article-title><source>J Clin Ultrasound</source><volume>33</volume><fpage>442</fpage><lpage>446</lpage><year>2005</year><pub-id pub-id-type="pmid">16281263</pub-id><pub-id pub-id-type="doi">10.1002/jcu.20163</pub-id></element-citation></ref>
<ref id="b13-ETM-29-4-12837"><label>13</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Defrancis</surname><given-names>N</given-names></name><name><surname>Klosk</surname><given-names>E</given-names></name><name><surname>Albano</surname><given-names>E</given-names></name></person-group><article-title>Needlebiopsy of theparietalpleura</article-title><source>N Engl J Med</source><volume>252</volume><fpage>948</fpage><lpage>949</lpage><year>1995</year><pub-id pub-id-type="pmid">14370459</pub-id><pub-id pub-id-type="doi">10.1056/NEJM195506022522206</pub-id></element-citation></ref>
<ref id="b14-ETM-29-4-12837"><label>14</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Benamore</surname><given-names>RE</given-names></name><name><surname>Scott</surname><given-names>K</given-names></name><name><surname>Richards</surname><given-names>CJ</given-names></name><name><surname>Entwisle</surname><given-names>JJ</given-names></name></person-group><article-title>Image guided pleura biopsy: Diagnostic yield and complications</article-title><source>Clin Radiol</source><volume>61</volume><fpage>700</fpage><lpage>705</lpage><year>2006</year><pub-id pub-id-type="pmid">16843755</pub-id><pub-id pub-id-type="doi">10.1016/j.crad.2006.05.002</pub-id></element-citation></ref>
<ref id="b15-ETM-29-4-12837"><label>15</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Christopher</surname><given-names>DJ</given-names></name><name><surname>Schumacher</surname><given-names>SG</given-names></name><name><surname>Michael</surname><given-names>JS</given-names></name><name><surname>Luo</surname><given-names>R</given-names></name><name><surname>Balamugesh</surname><given-names>T</given-names></name><name><surname>Duraikannan</surname><given-names>P</given-names></name><name><surname>Pollock</surname><given-names>NR</given-names></name><name><surname>Pai</surname><given-names>M</given-names></name><name><surname>Denkinger</surname><given-names>CM</given-names></name></person-group><article-title>Performance of Xpert MTB/RIF on pleural tissue for the diagnosis of pleural tuberculosis</article-title><source>Eur Respir J</source><volume>42</volume><fpage>1427</fpage><lpage>1429</lpage><year>2013</year><pub-id pub-id-type="pmid">23900990</pub-id><pub-id pub-id-type="doi">10.1183/09031936.00103213</pub-id></element-citation></ref>
<ref id="b16-ETM-29-4-12837"><label>16</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Diacon</surname><given-names>AH</given-names></name><name><surname>Van de Wal</surname><given-names>BW</given-names></name><name><surname>Wyser</surname><given-names>C</given-names></name><name><surname>Smedema</surname><given-names>JP</given-names></name><name><surname>Bezuidenhout</surname><given-names>J</given-names></name><name><surname>Bolliger</surname><given-names>CT</given-names></name><name><surname>Walzl</surname><given-names>G</given-names></name></person-group><article-title>Diagnostic tools in tuberculous pleurisy: A direct comparative study</article-title><source>Eur Respir J</source><volume>22</volume><fpage>589</fpage><lpage>591</lpage><year>2003</year><pub-id pub-id-type="pmid">14582908</pub-id><pub-id pub-id-type="doi">10.1183/09031936.03.00017103a</pub-id></element-citation></ref>
<ref id="b17-ETM-29-4-12837"><label>17</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Steingart</surname><given-names>KR</given-names></name><name><surname>Schiller</surname><given-names>I</given-names></name><name><surname>Horne</surname><given-names>DJ</given-names></name><name><surname>Pai</surname><given-names>M</given-names></name><name><surname>Boehme</surname><given-names>CC</given-names></name><name><surname>Dendukuri</surname><given-names>N</given-names></name></person-group><article-title>Xpert<sup>&#x00AE;</sup> MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults</article-title><source>Cochrane Database Syst Rev</source><volume>2014</volume><issue>CD009593</issue><year>2014</year><pub-id pub-id-type="pmid">24448973</pub-id><pub-id pub-id-type="doi">10.1002/14651858.CD009593.pub3</pub-id></element-citation></ref>
<ref id="b18-ETM-29-4-12837"><label>18</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Blakemore</surname><given-names>R</given-names></name><name><surname>Story</surname><given-names>E</given-names></name><name><surname>Helb</surname><given-names>D</given-names></name><name><surname>Kop</surname><given-names>J</given-names></name><name><surname>Banada</surname><given-names>P</given-names></name><name><surname>Owens</surname><given-names>MR</given-names></name><name><surname>Chakravorty</surname><given-names>S</given-names></name><name><surname>Jones</surname><given-names>M</given-names></name><name><surname>Alland</surname><given-names>D</given-names></name></person-group><article-title>Evaluation of the analytical performance of the Xpert MTB/RIF assay</article-title><source>J Clin Microbiol</source><volume>48</volume><fpage>2495</fpage><lpage>2501</lpage><year>2010</year><pub-id pub-id-type="pmid">20504986</pub-id><pub-id pub-id-type="doi">10.1128/JCM.00128-10</pub-id></element-citation></ref>
<ref id="b19-ETM-29-4-12837"><label>19</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Denkinger</surname><given-names>CM</given-names></name><name><surname>Schumacher</surname><given-names>SG</given-names></name><name><surname>Boehme</surname><given-names>CC</given-names></name><name><surname>Dendukuri</surname><given-names>N</given-names></name><name><surname>Pai</surname><given-names>M</given-names></name><name><surname>Steingart</surname><given-names>KR</given-names></name></person-group><article-title>Xpert MTB/RIF assay for the diagnosis of extrapulmonary tuberculosis: A systematic review and meta-analysis</article-title><source>Eur Respir J</source><volume>44</volume><fpage>435</fpage><lpage>446</lpage><year>2014</year><pub-id pub-id-type="pmid">24696113</pub-id><pub-id pub-id-type="doi">10.1183/09031936.00007814</pub-id></element-citation></ref>
<ref id="b20-ETM-29-4-12837"><label>20</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Koegelenberg</surname><given-names>CF</given-names></name><name><surname>Irusen</surname><given-names>EM</given-names></name><name><surname>von Groote-Bidlingmaier</surname><given-names>F</given-names></name><name><surname>Bruwer</surname><given-names>JW</given-names></name><name><surname>Batubara</surname><given-names>EM</given-names></name><name><surname>Diacon</surname><given-names>AH</given-names></name></person-group><article-title>The utility of ultrasound-guided thoracentesis and pleural biopsy in undiagnosed pleural exudates</article-title><source>Thorax</source><volume>70</volume><fpage>995</fpage><lpage>997</lpage><year>2015</year><pub-id pub-id-type="pmid">25997433</pub-id><pub-id pub-id-type="doi">10.1136/thoraxjnl-2014-206567</pub-id></element-citation></ref>
<ref id="b21-ETM-29-4-12837"><label>21</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Saeed</surname><given-names>M</given-names></name><name><surname>Ahmad</surname><given-names>M</given-names></name><name><surname>Iram</surname><given-names>S</given-names></name><name><surname>Riaz</surname><given-names>S</given-names></name><name><surname>Akhtar</surname><given-names>M</given-names></name><name><surname>Aslam</surname><given-names>M</given-names></name></person-group><article-title>A breakthrough for the diagnosis of tuberculous pericarditis and pleuritisin less than 2 hours</article-title><source>Saudi Med J</source><volume>38</volume><fpage>699</fpage><lpage>705</lpage><year>2017</year><pub-id pub-id-type="pmid">28674714</pub-id><pub-id pub-id-type="doi">10.15537/smj.2017.7.17694</pub-id></element-citation></ref>
<ref id="b22-ETM-29-4-12837"><label>22</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Haijing</surname><given-names>Z</given-names></name><name><surname>Chengyong</surname><given-names>L</given-names></name><name><surname>Dongqing</surname><given-names>Z</given-names></name></person-group><article-title>Application value of GeneXpert MTB/RIF system in rapid diagnosis of tuberculous pleurisy)</article-title><source>Beijing Med J</source><volume>38</volume><fpage>739</fpage><lpage>741</lpage><year>2016</year></element-citation></ref>
<ref id="b23-ETM-29-4-12837"><label>23</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sun</surname><given-names>W</given-names></name><name><surname>Gu</surname><given-names>J</given-names></name><name><surname>Bi</surname><given-names>K</given-names></name><name><surname>Zhang</surname><given-names>Y</given-names></name><name><surname>Shen</surname><given-names>MJ</given-names></name><name><surname>Wang</surname><given-names>Y</given-names></name><name><surname>Fan</surname><given-names>L</given-names></name></person-group><article-title>Clinical performance of Xpert MTB/RIF on contrast-enhanced ultrasound-guided core biopsy specimens for rapid diagnosis of superficial tuberculous lymphadenitis in high TB burden settings</article-title><source>Infection</source><volume>49</volume><fpage>653</fpage><lpage>660</lpage><year>2021</year><pub-id pub-id-type="pmid">33543403</pub-id><pub-id pub-id-type="doi">10.1007/s15010-021-01578-w</pub-id></element-citation></ref>
<ref id="b24-ETM-29-4-12837"><label>24</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gu</surname><given-names>Y</given-names></name><name><surname>Wang</surname><given-names>G</given-names></name><name><surname>Dong</surname><given-names>W</given-names></name><name><surname>Li</surname><given-names>Y</given-names></name><name><surname>Ma</surname><given-names>Y</given-names></name><name><surname>Shang</surname><given-names>Y</given-names></name><name><surname>Qin</surname><given-names>S</given-names></name><name><surname>Huang</surname><given-names>H</given-names></name></person-group><article-title>Xpert MTB/RIF and GenoType MTBDRplus assays for the rapid diagnosis of bone and joint tuberculosis</article-title><source>Infect Dis</source><volume>36</volume><fpage>27</fpage><lpage>30</lpage><year>2015</year><pub-id pub-id-type="pmid">26004172</pub-id><pub-id pub-id-type="doi">10.1016/j.ijid.2015.05.014</pub-id></element-citation></ref>
<ref id="b25-ETM-29-4-12837"><label>25</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yu</surname><given-names>C</given-names></name><name><surname>Xuhui</surname><given-names>L</given-names></name><name><surname>Liang</surname><given-names>F</given-names></name></person-group><article-title>Diagnostic value of genexp ERT m TB/RIF in HIV negative urinary tuberculosis</article-title><source>Chin J Tuberculosis</source><volume>39</volume><fpage>1100</fpage><lpage>1106</lpage><year>2017</year></element-citation></ref>
<ref id="b26-ETM-29-4-12837"><label>26</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bahr</surname><given-names>NC</given-names></name><name><surname>Marais</surname><given-names>S</given-names></name><name><surname>Caws</surname><given-names>M</given-names></name><name><surname>van Crevel</surname><given-names>R</given-names></name><name><surname>Wilkinson</surname><given-names>RJ</given-names></name><name><surname>Tyagi</surname><given-names>JS</given-names></name><name><surname>Thwaites</surname><given-names>GE</given-names></name><name><surname>Boulware</surname><given-names>DR</given-names></name></person-group><comment>Tuberculous Meningitis International Research Consortium</comment><article-title>GeneXpert MTB/Rif to diagnose tuberculous meningitis: Perhaps the first test but not the last</article-title><source>Clin Infect Dis</source><volume>62</volume><fpage>1133</fpage><lpage>1135</lpage><year>2016</year><pub-id pub-id-type="pmid">26966284</pub-id><pub-id pub-id-type="doi">10.1093/cid/ciw083</pub-id></element-citation></ref>
</ref-list>
</back>
<floats-group>
<fig id="f1-ETM-29-4-12837" position="float">
<label>Figure 1</label>
<caption><p>Flow diagram. CEUS, contrast-enhanced ultrasound.</p></caption>
<graphic xlink:href="etm-29-04-12837-g00.tif" />
</fig>
<fig id="f2-ETM-29-4-12837" position="float">
<label>Figure 2</label>
<caption><p>Ultrasound images. (A) Ultrasound imaging can clearly display pleural hypoechoic lesions, outlined by orange lines in the figure. (B) When performing biopsy on pleural lesions under ultrasound display, ultrasound can clearly show the biopsy needle (orange arrow).</p></caption>
<graphic xlink:href="etm-29-04-12837-g01.tif" />
</fig>
<fig id="f3-ETM-29-4-12837" position="float">
<label>Figure 3</label>
<caption><p>Acid resistant staining image. (A) The figure clearly shows the acid fast staining results of a patient with pleural tuberculosis. <italic>M. tuberculosis</italic> was stained blue. Magnification, x1,000. There are a large number of <italic>M. tuberculosis</italic>; (B) The figure clearly shows the acid fast staining results of another patient with pleural tuberculosis. <italic>M. tuberculosis</italic> was stained blue. Magnification, x1,000. The number of <italic>M. tuberculosis</italic> is relatively small.</p></caption>
<graphic xlink:href="etm-29-04-12837-g02.tif" />
</fig>
<fig id="f4-ETM-29-4-12837" position="float">
<label>Figure 4</label>
<caption><p>ROC curve of pathology and three test techniques in the diagnosis of pleural tuberculosis. ROC, receiver operating characteristic curve; MTB/RIF, <italic>Mycobacterium tuberculosis</italic>/resistance to rifampin.</p></caption>
<graphic xlink:href="etm-29-04-12837-g03.tif" />
</fig>
<table-wrap id="tI-ETM-29-4-12837" position="float">
<label>Table I</label>
<caption><p>Diagnosis results of pathology and three detection techniques for pleural tuberculosis.</p></caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="middle" colspan="2">&#x00A0;</th>
<th align="center" valign="middle" colspan="3">Clinical comprehensive diagnosis</th>
</tr>
<tr>
<th align="left" valign="middle">Detection techniques</th>
<th align="center" valign="middle">Detection result</th>
<th align="center" valign="middle">Chest wall tuberculosis (n)</th>
<th align="center" valign="middle">Non chest wall tuberculosis (n)</th>
<th align="center" valign="middle">Total (n)</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="middle">Pathology</td>
<td align="left" valign="middle">Positive</td>
<td align="center" valign="middle">24</td>
<td align="center" valign="middle">0</td>
<td align="center" valign="middle">24</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Negative</td>
<td align="center" valign="middle">3</td>
<td align="center" valign="middle">19</td>
<td align="center" valign="middle">22</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Total</td>
<td align="center" valign="middle">27</td>
<td align="center" valign="middle">19</td>
<td align="center" valign="middle">46</td>
</tr>
<tr>
<td align="left" valign="middle">Acid-fast staining</td>
<td align="left" valign="middle">Positive</td>
<td align="center" valign="middle">5</td>
<td align="center" valign="middle">0</td>
<td align="center" valign="middle">5</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Negative</td>
<td align="center" valign="middle">22</td>
<td align="center" valign="middle">19</td>
<td align="center" valign="middle">41</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Total</td>
<td align="center" valign="middle">27</td>
<td align="center" valign="middle">19</td>
<td align="center" valign="middle">46</td>
</tr>
<tr>
<td align="left" valign="middle"><italic>Mycobacterium</italic> tuberculosis culture</td>
<td align="left" valign="middle">Positive</td>
<td align="center" valign="middle">4</td>
<td align="center" valign="middle">0</td>
<td align="center" valign="middle">4</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Negative</td>
<td align="center" valign="middle">23</td>
<td align="center" valign="middle">19</td>
<td align="center" valign="middle">42</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Total</td>
<td align="center" valign="middle">27</td>
<td align="center" valign="middle">19</td>
<td align="center" valign="middle">46</td>
</tr>
<tr>
<td align="left" valign="middle">GeneXpert MTB/RIF</td>
<td align="left" valign="middle">Positive</td>
<td align="center" valign="middle">26</td>
<td align="center" valign="middle">1</td>
<td align="center" valign="middle">27</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Negative</td>
<td align="center" valign="middle">1</td>
<td align="center" valign="middle">18</td>
<td align="center" valign="middle">19</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Total</td>
<td align="center" valign="middle">27</td>
<td align="center" valign="middle">19</td>
<td align="center" valign="middle">46</td>
</tr>
<tr>
<td align="left" valign="middle">Pathology and Acid-fast staining</td>
<td align="left" valign="middle">Positive</td>
<td align="center" valign="middle">24</td>
<td align="center" valign="middle">0</td>
<td align="center" valign="middle">24</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Negative</td>
<td align="center" valign="middle">3</td>
<td align="center" valign="middle">19</td>
<td align="center" valign="middle">22</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Total</td>
<td align="center" valign="middle">27</td>
<td align="center" valign="middle">19</td>
<td align="center" valign="middle">46</td>
</tr>
<tr>
<td align="left" valign="middle">Pathology and <italic>Mycobacterium</italic> tuberculosis culture</td>
<td align="left" valign="middle">Positive</td>
<td align="center" valign="middle">24</td>
<td align="center" valign="middle">0</td>
<td align="center" valign="middle">24</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Negative</td>
<td align="center" valign="middle">3</td>
<td align="center" valign="middle">19</td>
<td align="center" valign="middle">22</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Total</td>
<td align="center" valign="middle">27</td>
<td align="center" valign="middle">19</td>
<td align="center" valign="middle">46</td>
</tr>
<tr>
<td align="left" valign="middle">Pathology and GeneXpert MTB/RIF</td>
<td align="left" valign="middle">Positive</td>
<td align="center" valign="middle">27</td>
<td align="center" valign="middle">1</td>
<td align="center" valign="middle">28</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Negative</td>
<td align="center" valign="middle">0</td>
<td align="center" valign="middle">18</td>
<td align="center" valign="middle">18</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Total</td>
<td align="center" valign="middle">27</td>
<td align="center" valign="middle">19</td>
<td align="center" valign="middle">46</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn><p>MTB/RIF, <italic>Mycobacterium tuberculosis</italic>/resistance to rifampin.</p></fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="tII-ETM-29-4-12837" position="float">
<label>Table II</label>
<caption><p>Diagnostic value of pathology and three detection techniques for pleural tuberculosis.</p></caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="middle">Detection techniques</th>
<th align="center" valign="middle">AUC</th>
<th align="center" valign="middle">Sensitivity (&#x0025;)</th>
<th align="center" valign="middle">Specificity (&#x0025;)</th>
<th align="center" valign="middle">Positive predictive value (&#x0025;)</th>
<th align="center" valign="middle">Negative predictive value (&#x0025;)</th>
<th align="center" valign="middle">&#x03BA;-value</th>
<th align="center" valign="middle">P-value</th>
<th align="center" valign="middle">Total coincidence rate (&#x0025;)</th>
<th align="center" valign="middle">Jordan index (&#x0025;)</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="middle">Pathology</td>
<td align="center" valign="middle">0.944</td>
<td align="center" valign="middle">88.89</td>
<td align="center" valign="middle">100.00</td>
<td align="center" valign="middle">100.00</td>
<td align="center" valign="middle">86.36</td>
<td align="center" valign="middle">0.869</td>
<td align="center" valign="middle">0.000</td>
<td align="center" valign="middle">93.48</td>
<td align="center" valign="middle">88.89</td>
</tr>
<tr>
<td align="left" valign="middle">Acid-fast staining</td>
<td align="center" valign="middle">0.593</td>
<td align="center" valign="middle">18.52</td>
<td align="center" valign="middle">100.00</td>
<td align="center" valign="middle">100.00</td>
<td align="center" valign="middle">46.34</td>
<td align="center" valign="middle">0.158</td>
<td align="center" valign="middle">0.047</td>
<td align="center" valign="middle">52.17</td>
<td align="center" valign="middle">18.52</td>
</tr>
<tr>
<td align="left" valign="middle"><italic>Mycobac-</italic> <italic>terium</italic> tuberculosis culture</td>
<td align="center" valign="middle">0.574</td>
<td align="center" valign="middle">14.81</td>
<td align="center" valign="middle">100.00</td>
<td align="center" valign="middle">100.00</td>
<td align="center" valign="middle">45.24</td>
<td align="center" valign="middle">0.126</td>
<td align="center" valign="middle">0.079</td>
<td align="center" valign="middle">50.00</td>
<td align="center" valign="middle">14.81</td>
</tr>
<tr>
<td align="left" valign="middle">GeneXpert MTB/RIF</td>
<td align="center" valign="middle">0.955</td>
<td align="center" valign="middle">96.30</td>
<td align="center" valign="middle">94.74</td>
<td align="center" valign="middle">96.30</td>
<td align="center" valign="middle">94.74</td>
<td align="center" valign="middle">0.910</td>
<td align="center" valign="middle">0.000</td>
<td align="center" valign="middle">95.65</td>
<td align="center" valign="middle">91.03</td>
</tr>
<tr>
<td align="left" valign="middle">Pathology and Acid-fast staining</td>
<td align="center" valign="middle">0.944</td>
<td align="center" valign="middle">88.89</td>
<td align="center" valign="middle">100.00</td>
<td align="center" valign="middle">100.00</td>
<td align="center" valign="middle">86.36</td>
<td align="center" valign="middle">0.869</td>
<td align="center" valign="middle">0.000</td>
<td align="center" valign="middle">93.48</td>
<td align="center" valign="middle">88.89</td>
</tr>
<tr>
<td align="left" valign="middle">Pathology and <italic>Mycobac-</italic> <italic>terium</italic> tuberculosis culture</td>
<td align="center" valign="middle">0.944</td>
<td align="center" valign="middle">88.89</td>
<td align="center" valign="middle">100.00</td>
<td align="center" valign="middle">100.00</td>
<td align="center" valign="middle">86.36</td>
<td align="center" valign="middle">0.869</td>
<td align="center" valign="middle">0.000</td>
<td align="center" valign="middle">93.48</td>
<td align="center" valign="middle">88.89</td>
</tr>
<tr>
<td align="left" valign="middle">Pathology and Gene Xpert MTB/RIF</td>
<td align="center" valign="middle">0.974</td>
<td align="center" valign="middle">100.00</td>
<td align="center" valign="middle">94.74</td>
<td align="center" valign="middle">96.43</td>
<td align="center" valign="middle">100.00</td>
<td align="center" valign="middle">0.955</td>
<td align="center" valign="middle">0.000</td>
<td align="center" valign="middle">97.83</td>
<td align="center" valign="middle">94.74</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn><p>Results showed that the AUC of pathology combined with GeneXpert MTB/RIF was the largest. AUC, area under curve; MTB/RIF, <italic>Mycobacterium tuberculosis</italic>/resistance to rifampin.</p></fn>
</table-wrap-foot>
</table-wrap>
</floats-group>
</article>
