scholarly journals The Value of FujiLAM in the Diagnosis of Tuberculosis: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhenzhen Li ◽  
Xiang Tong ◽  
Sitong Liu ◽  
Jirong Yue ◽  
Hong Fan
Keyword(s):  
Likelihood Ratio ◽  
Sensitivity And Specificity ◽  
Cell Envelope ◽  
Meta Analysis ◽  
Positive Likelihood Ratio ◽  
Negative Likelihood Ratio ◽  
Diagnostic Value ◽  
Reference Standard ◽  
Cell Counts ◽  
Potential Biomarker

Background: Timely and accurate diagnosis of tuberculosis (TB) remains a major challenge. Lipoarabinomannan (LAM) is a specific component of the cell envelope of Mycobacterium tuberculosis and is also a potential biomarker for the diagnosis of TB. Recently, the Fujifilm SILVAMP TB LAM test (FujiLAM), as a novel urine lateral flow LAM test, was developed for the diagnosis of TB and is convenient and timely. Because of a difference in the diagnostic value of FujiLAM in the original studies, we conducted a meta-analysis to comprehensively assess the diagnostic value of FujiLAM in TB.Data Sources: We performed a literature search using the PubMed and EMBASE databases and commercial Internet search engines to identify studies.Methods: Searches of databases using relevant terms (“tuberculosis” or “TB”) and (“Fujifilm SILVAMP TB LAM” or “FujiLAM”) were performed. Screening, study reviewing, data extracting and assessing data quality was performed independently by two reviewers. We calculated the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio. To minimize potential heterogeneity, we performed subgroup analyses.Results: Nine articles were included in the meta-analysis. When using the microbiological reference standard (MRS), the results showed that the sensitivity and specificity of FujiLAM were 0.70 and 0.93, respectively, in adults with TB, while the sensitivity and specificity of FujiLAM in children with TB were 0.51 and 0.87. When using a comprehensive reference standard (CRS), the sensitivity and specificity of FujiLAM in adults with TB were 0.59 and 0.96, respectively, while the results showed that the sensitivity and specificity of FujiLAM in children with TB were 0.27 and 0.86, respectively. Subgroup analysis showed that FujiLAM had higher diagnostic sensitivity in patients with human immunodeficiency virus infection or CD4 cell counts < 200 cells/μL, both in adults and children.Conclusions: This meta-analysis suggests that FujiLAM has a high value in the diagnosis of adults with TB.

scholarly journals Diagnostic and Prognostic Role of miR-192 in Different Cancers: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Lili Wang ◽  
Yuhan Liu ◽  
Chen Lyu ◽  
Alexander Buchner ◽  
Heike Pohla
Keyword(s):  
Systematic Review ◽  
Likelihood Ratio ◽  
Sensitivity And Specificity ◽  
Meta Analysis ◽  
Positive Likelihood Ratio ◽  
Negative Likelihood Ratio ◽  
Cochrane Library ◽  
Eligibility Criteria ◽  
Potential Biomarker

Introduction. It has been shown that miR-192 is abnormally expressed in a variety of cancer types and participates in different kinds of signaling pathways. The role of miR-192 in the diagnosis and prognosis of cancer has not been verified. This article is aimed at exploring the diagnostic and prognostic value of miR-192 through a systematic review and meta-analysis. Methods. A systematic search was performed through PubMed, Embase, Web of Science, and Cochrane Library databases up to June 16, 2020. A total of 16 studies were enrolled in the meta-analyses, of which 11 articles were used for diagnostic meta-analysis and 5 articles were used for prognostic meta-analysis. The values of sensitivity and specificity using miR-192 expression as a diagnostic tool were pooled in the diagnostic meta-analysis. The hazard ratios (HRs) of overall survival (OS) with 95 confidence intervals (CIs) were extracted from the studies, and pooled HRs were evaluated in the prognostic meta-analysis. Eleven studies including 667 cancer patients and 514 controls met the eligibility criteria for the diagnostic meta-analysis. Five studies including 166 patients with high miR-192 expression and 236 patients with low miR-192 expression met the eligibility criteria for the prognostic meta-analysis. Results. The overall diagnostic accuracy was as follows: sensitivity 0.79 ( 95 % CI = 0.75 -0.82), specificity 0.74 ( 95 % CI = 0.64 -0.82), positive likelihood ratio 3.03 ( 95 % CI = 2.11 -4.34), negative likelihood ratio 0.29 ( 95 % CI = 0.23 -0.37), diagnostic odds ratio 10.50 ( 95 % CI = 5.89 -18.73), and area under the curve ratio (AUC) 0.82 ( 95 % CI = 0.78 -0.85). The overall prognostic analysis showed that high expression of miR-192 in patients was associated with positive survival ( HR = 0.62 , 95 % CI : 0.41 -0.93, p = 0.020 ). Conclusion. Our results revealed that miR-192 was a potential biomarker with good sensitivity and specificity in cancers. Moreover, highly expressed miR-192 predicted a good prognosis for patients.

scholarly journals Diagnostic Accuracy of Epithelial Membrane Antigen for Malignant Effusions: A Meta-Analysis

2016 ◽  
Vol 31 (1) ◽  
pp. 11-16 ◽  
Author(s):  
Wentao Lin ◽  
Xiaoxue Liu ◽  
Ying Cen
Keyword(s):  
Likelihood Ratio ◽  
Sensitivity And Specificity ◽  
Odds Ratio ◽  
Epithelial Membrane Antigen ◽  
Meta Analysis ◽  
Positive Likelihood Ratio ◽  
Negative Likelihood Ratio ◽  
Diagnostic Odds Ratio ◽  
Diagnostic Potential ◽  
Malignant Effusions

Background and Objectives Body cavity fluid examination sometimes presents a diagnostic challenge in cytology practice. This meta-analysis was undertaken to comprehensively assess the diagnostic potential of epithelial membrane antigen (EMA) in malignant effusions. Materials and Methods All relevant original articles about EMA in the diagnosis of malignant effusions published up to July 1, 2014 were retrieved. The overall sensitivity, specificity, positive and negative likelihood ratio, diagnostic odds ratio, and summary receiver operating characteristic (SROC) curve were pooled to evaluate the diagnostic value of EMA for malignant effusions using the Meta-Disc 1.4 and STATA 12.0 statistical software. Results Eleven studies met the inclusion criteria for the meta-analysis and the summary estimates for EMA in the diagnosis of malignant effusions were as follows: sensitivity 0.9 (95% CI 0.83-0.87), specificity 0.87 (95% CI 0.96-0.99), positive likelihood ratio 5.8 (95% CI 15.59-36.37), negative likelihood ratio 0.15 (95% CI 0.07-0.20) and diagnostic odds ratio 52.63 (95% CI 20.91-132.49). The SROC curve indicated that the maximum joint sensitivity and specificity (Q-value) was 0.88; the area under the curve was 0.94. Conclusion The present meta-analysis indicated that EMA may be a useful diagnostic tool with good sensitivity and specificity for differentiating malignant effusions from benign effusions.

scholarly journals Diagnostic value of endobronchial ultrasound elastography for differentiating benign and malignant hilar and mediastinal lymph nodes: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Jiangfeng Wu ◽  
Yue Sun ◽  
Yunlai Wang ◽  
Lijing Ge ◽  
Yun Jin ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Likelihood Ratio ◽  
Meta Analysis ◽  
Area Under The Curve ◽  
Positive Likelihood Ratio ◽  
Negative Likelihood Ratio ◽  
Diagnostic Value ◽  
Endobronchial Ultrasound ◽  
Mediastinal Lymph Nodes ◽  
Sensitivity Specificity

Aims: In the present study, a meta-analysis was performed to evaluate the diagnostic value of endobronchial ultrasound (EBUS) elastography for differentiating benign and malignant hilar and mediastinal lymph nodes (LNs). Material and methods: A comprehensive literature search was carried out through PubMed, Embase, and Cochrane Library. Two authors screened the papers and extracted the data independently and any discrepancies were resolved by discussion. The methodolog-ical quality of each included study was assessed by the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and area under the curve were calculated to evaluate the value of EBUS elastography for hilar and mediastinal LNs. Results: Seventeen studies with the number of 2307 LNs were included. There was significant heterogeneity across the included studies. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio for the diagnosis of hilar and mediastinal LNs by EBUS elastography were 0.90 (95% confidence interval [CI], 0.84-0.94), 0.78 (95% CI, 0.74-0.81), 4.1 (95% CI, 3.4-4.9), 0.12 (95% CI, 0.07-0.21) and 33 (95% CI, 17-64), respectively. Furthermore, area under the curve was calculated to be 0.86 (95% CI, 0.82-0.88). Conclusion: EBUS elastography is a valuable technology in the differentiation of benign and malignant hilar and mediastinal LNs and could provide supplementary diagnostic information during endobronchial ultrasound-guided transbronchial needle aspiration. The combination of EBUS elastography and B-mode EBUS could improve the diagnostic accuracy for hilar and mediastinal LNs.

scholarly journals ­Silent Existence of Eosinopenia in Sepsis: A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Yao Lin ◽  
Jiabing Rong ◽  
Zhaocai Zhang
Keyword(s):  
Likelihood Ratio ◽  
Meta Analysis ◽  
Characteristic Curve ◽  
False Negative ◽  
Positive Likelihood Ratio ◽  
Negative Likelihood Ratio ◽  
Medical Emergency ◽  
Cochrane Central Register ◽  
Analysis Model ◽  
Potential Biomarker

Abstract BackgroundSepsis is a life-threatening and time-critical medical emergency; therefore, the early diagnosis of sepsis is essential to timely treatment and favorable outcomes for patients susceptible to sepsis. Eosinopenia has been identified as a potential biomarker of sepsis in the past decade. However, its clinical application progress is slow and its recognition is low. Recent studies have again focused on the potential association between Eosinopenia and severe infections. This study analyzed the efficacy of Eosinopenia as a biomarker for diagnosis of sepsis and its correlation with pathophysiology of sepsis.MethodWe searched PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials CENTRAL databases to identify studies that met the inclusion criteria. Two authors performed data extraction independently. The pooled outcomes were calculated by TP (true positive), FP (false positive), FN (false negative), TN (true negative) by using bivariate meta-analysis model in STATA 14.0 software. Meanwhile, possible mechanisms of sepsis induced Eosinopenia was also analyzed.ResultsSeven studies were included in the present study with a total number of 3842 subjects. The incidence of Eosinopenia based on the enrolled studies varied from 23.2% to 92.7%. For diagnosis of sepsis, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of Eosinopenia were 0.66 (95%CI [0.53-0.77]), 0.68 (95%CI [0.56-0.79]), 2.09 (95%CI [1.44-3.02]), 0.49 (95%CI [0.34-0.71]) and 4.23 (95%CI [2.15-8.31]), respectively. The area under the summary receiver operator characteristic curve (SROC) was 0.73 (95%CI [0.68-0.76]). Meta-regression analysis revealed that no single parameter accounted for the heterogeneity of pooled outcomes. For each subgroup of different eosinopenia cutoff values (50, 40, ≤25, 100), the sensitivity was 0.61, 0.79, 0.57, 0.54, and the specificity was 0.61, 0.75, 0.83, 0.51, respectively. ConclusionsOur findings suggested that Eosinopenia has a high incidence in sepsis but has no superiority in comparison with conventional biomarkers for diagnosis of sepsis. However, eosinopenia can still be used in clinical diagnosis for sepsis as a simple, convenient, fast and inexpensive biomarker. Therefore, further large clinical trials are still needed to re-evaluate eosinopenia as a biomarker of sepsis.

scholarly journals The value of miR-155 as a biomarker for the diagnosis and prognosis of lung cancer: a systematic review with meta-analysis

2019 ◽  
Author(s):  
Chuchu Shao ◽  
Fengming Yang ◽  
Zhiqiang Qin ◽  
Xinming Jing ◽  
Yongqian Shu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Likelihood Ratio ◽  
Meta Analysis ◽  
Positive Likelihood Ratio ◽  
Disease Free Survival ◽  
Negative Likelihood Ratio ◽  
Free Survival ◽  
Diagnosis And Prognosis ◽  
Potential Biomarker

Abstract Background: Recently, a growing number of studies have reported the coorelation between miR-155 and the diagnosis and prognosis of lung cancer, but results of these researches were still controversial due to insufficient sample size. Thus, we carried out the systematic review and meta-analysis to figure out whether miR-155 could be a screening tool in the detection and prognosis of lung cancer. Methods: A meta-analysis of 13 articles with 19 studies was performed by retrieving the PubMed, Embase and Web of Science. We screened all correlated literaters until December 1st, 2018. For the diagnosis analysis of miR-155 in lung cancer, sensitivity(SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the ROC curve (AUC) were pooled to evaluate the accuracy of miRNA-155 in the diagnosis of lung cancer. For the prognosis analysis of miR-155 in lung cancer, the pooled HRs and 95% CIs of miR-155 for overall survival/disease free survival/progression-free survival (OS/DFS/PFS) were calculated. In addition, Subgroup and meta-regression analyses were performed to distinguish the potential sources of heterogeneity between studies. Results: For the diagnostic analysis of miR-155 in lung cancer, the pooled SEN and SPE were 0.82 (95% CI: 0.72-0.88) and 0.78 (95% CI: 0.71-0.84), respectively. Besides, the pooled PLR was 3.75 (95% CI: 2.76-5.10), NLR was 0.23 (95% CI: 0.15-0.37), DOR was 15.99 (95% CI: 8.11-31.52) and AUC was 0.87 (95% CI: 0.84-0.90), indicating a significant value of miR-155 in the lung cancer detection. For the prognostic analysis of miR-155 in lung cancer, up-regulated miRNA-155 expression was not significantly associated with a poor OS (pooled HR = 1.26, 95% CI: 0.66-2.40) or DFS/PFS (pooled HR = 1.28, 95% CI: 0.82-1.97). Conclusions: The present meta-analysis demonstrated that miR-155 could be a potential biomarker for the detection of lung cancer but not an effective biomarker for predicting the outcomes of lung cancer. Furthermore, more well-designed researches with larger cohorts were warranted to confirm the value of miR-155 for the diagnosis and prognosis of lung cancer.

scholarly journals Meta-analysis of serum and/or plasma D-dimer in the diagnosis of periprosthetic joint infection

2020 ◽  
Author(s):  
Cheng Li ◽  
Donara Margaryan ◽  
Cristina Ojeda-Thies ◽  
Carsten Perka ◽  
Andrej Trampuz
Keyword(s):  
Likelihood Ratio ◽  
Periprosthetic Joint Infection ◽  
Degradation Products ◽  
Meta Analysis ◽  
Joint Infection ◽  
Positive Likelihood Ratio ◽  
Negative Likelihood Ratio ◽  
Diagnostic Value ◽  
Medical Subject Headings ◽  
D Dimer

Abstract Background The purpose of this meta-analysis was to evaluate the diagnostic value of D-dimer in detecting periprosthetic joint infection (PJI). Methods A systematic search and screen of relevant studies was performed in the PubMed, Web of Science and Embase databases using the following medical subject headings (MeSH) or keywords: “arthroplasty or joint prosthesis or joint replacement or periprosthetic joint or prosthetic joint”, “infection or infectious or infected”, and “D-dimer or serum D-dimer or plasma D-dimer or fibrin degradation products”. Then, the data were analysed and processed by Meta-Disc software. Results A total of 7 studies with 1285 patients were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) were 0.75 (95% confidence interval [CI]: 0.70 to 0.79), 0.69 (95% CI: 0.66 to 0.72), 3.01 (95% CI: 1.84 to 4.93), 0.32 (95% CI: 0.19 to 0.53) and 10.20 (95% CI: 3.63 to 28.64), respectively. Subgroup analyses showed that use of serum D-dimer had better sensitivity and specificity than plasma D-dimer for the diagnosis of PJI (0.86, 0.84 vs. 0.67, 0.60, respectively). Conclusion Serum D-dimer had a better diagnostic value than plasma D-dimer for the diagnosis of PJI.

scholarly journals A meta-analysis of circulating microRNAs in the diagnosis of papillary thyroid carcinoma

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251676
Author(s):  
Yan liu ◽  
Houfa Geng ◽  
Xuekui Liu ◽  
Mingfeng Cao ◽  
Xinhuan Zhang
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Likelihood Ratio ◽  
Meta Analysis ◽  
Positive Likelihood Ratio ◽  
Negative Likelihood Ratio ◽  
Diagnostic Value ◽  
Control Group ◽  
Papillary Thyroid ◽  
Circulating Micrornas

Background Aim of this meta-analysis was to evaluate the overall diagnostic value of circulating mini miRNAs for papillary thyroid carcinoma (PTC) and to find the possible molecular marker with higher diagnostic value for PTC. Methods We searched the Pubmed, Cochrane and Embase database until June 2020. We selected relevant literatures associated with the diagnosis of PTC with circulating miRNAs. The number of cases in experimental group and the control group, sensitivity and specificity could be extracted from the literatures. Results We got 9 literatures including 2114 cases of PTC. Comprehensive sensitivity was 0.79, comprehensive specificity was 0.82, positive likelihood ratio was 4.3, negative likelihood ratio was 0.26, diagnostic advantage ratio was 16. The summary receiver operating characteristic curve was drawn and the Area Under the Curve was 0.87. Conclusions Circulating microRNAs may be promising molecular markers for the diagnosis of papillary thyroid carcinoma. Combined detection of certain serum microRNAs can improve the diagnostic accuracy of papillary thyroid carcinoma. Especially MiR-222 and miR-146b may be prime candidates for the diagnosis of PTC in Asian population.

scholarly journals Meta-analysis of serum and/or plasma D-dimer in the diagnosis of periprosthetic joint infection

2020 ◽  
Author(s):  
Cheng Li ◽  
Donara Margaryan ◽  
Cristina Ojeda-Thies ◽  
Carsten Perka ◽  
Andrej Trampuz
Keyword(s):  
Likelihood Ratio ◽  
Periprosthetic Joint Infection ◽  
Degradation Products ◽  
Meta Analysis ◽  
Joint Infection ◽  
Positive Likelihood Ratio ◽  
Negative Likelihood Ratio ◽  
Diagnostic Value ◽  
Medical Subject Headings ◽  
D Dimer

Abstract Background The purpose of this meta-analysis was to evaluate the diagnostic value of D-dimer in detecting periprosthetic joint infection (PJI). Methods A systematic search and screening of relevant studies was performed in the databases PubMed, Web of Science, and Embase using the following medical subject headings (MeSH) or keywords: “arthroplasty or joint prosthesis or joint replacement or periprosthetic joint or prosthetic joint”, “infection or infectious or infected”, and “D-dimer or serum D-dimer or plasma D-dimer or fibrin degradation products”. Data were subsequently analysed and processed using Meta-Disc. Results Seven studies with 1285 patients were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.75 (95% confidence interval [CI]: 0.70–0.79), 0.69 (95% CI: 0.66–0.72), 3.01 (95% CI: 1.84–4.93), 0.32 (95% CI: 0.19–0.53), and 10.20 (95% CI: 3.63–28.64), respectively. Subgroup analyses showed that the use of serum D-dimer had better sensitivity and specificity than plasma D-dimer for the diagnosis of PJI . Conclusion Serum D-dimer was shown to have a better diagnostic value than plasma D-dimer for the diagnosis of PJI. Further research is required for clarification.

scholarly journals Diagnostic value of circulating tumor DNA as an effective biomarker in cervical cancer: a meta-analysis

2019 ◽  
Author(s):  
Yulan Gu ◽  
Chuandan Wan ◽  
Jiaming Qiu ◽  
Yanhong Cui ◽  
Tingwang Jiang
Keyword(s):  
Cervical Cancer ◽  
Likelihood Ratio ◽  
Large Scale ◽  
Meta Analysis ◽  
Characteristic Curve ◽  
Positive Likelihood Ratio ◽  
Negative Likelihood Ratio ◽  
Diagnostic Value ◽  
Circulating Tumor Dna ◽  
Tumor Dna

AbstractThe applications of liquid biopsy have attracted much attention in biomedical research in recent years. Circulating cell-free DNA (cfDNA) in the serum may serve as a unique tumor marker in various types of cancer. Circulating tumor DNA (ctDNA) is a type of serum cfDNA found in patients with cancer and contains abundant information regarding tumor characteristics, highlighting its potential diagnostic value in the clinical setting. However, the diagnostic value of cfDNA as a biomarker in cervical cancer remains unclear. Here, we performed a meta-analysis to evaluate the applications of ctDNA as a biomarker in cervical cancer. A systematic literature search was performed using PubMed, Embase, and WANFANG MED ONLINE databases up to March 18, 2019. All literature was analyzed using Meta Disc 1.4 and STATA 14.0 software. Diagnostic measures of accuracy of ctDNA in cervical cancer were pooled and investigated. Fifteen studies comprising 1109 patients with cervical cancer met our inclusion criteria and were subjected to analysis. The pooled sensitivity and specificity were 0.52 (95% confidence interval [CI], 0.33–0.71) and 0.97 (95% CI, 0.91–0.99), respectively. The pooled positive likelihood ratio and negative likelihood ratio were 16.0 (95% CI, 5.5–46.4) and 0.50 (95% CI, 0.33–0.75), respectively. The diagnostic odds ratio was 32 (95% CI, 10–108), and the area under the summary receiver operating characteristic curve was 0.92 (95% CI, 0.90– 0.94). There was no significant publication bias observed. In the included studies, ctDNA showed clear diagnostic value for diagnosing and monitoring cervical cancer. Our meta-analysis suggested that detection of human papilloma virus ctDNA in patients with cervical cancer could be used as a noninvasive early dynamic biomarker of tumors, with high specificity and moderate sensitivity. Further large-scale prospective studies are required to validate the factors that may influence the accuracy of cervical cancer diagnosis and monitoring.

scholarly journals Comparison of methods for the diagnosis of patent foramen ovale in patients with cryptogenic cerebral ischemia: a meta-analysis

2021 ◽  
Author(s):  
Xiaoxuan Guo ◽  
Xiaojuan Wang ◽  
Lu Zhang ◽  
Yan Zhang ◽  
Rui Peng ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Likelihood Ratio ◽  
Sensitivity And Specificity ◽  
Transthoracic Echocardiography ◽  
Patent Foramen Ovale ◽  
Meta Analysis ◽  
Positive Likelihood Ratio ◽  
Negative Likelihood Ratio ◽  
Receiver Operating Curve ◽  
Foramen Ovale

Background: Foramen ovale is a residual cavity in the developing heart in the fetus. At present, the standard methods for the diagnosis of PFO-right-to-left-shunting (PFO-RLS) include transesophageal echocardiography (TEE), contrast-transcranial Doppler echocardiography (C-TCD), and contrast-transthoracic echocardiography (C-TTE), each of them having its advantages and disadvantages.However, there are no data allowing the comparison of these three methods. Methods: We systematically reviewed all published studies on patients with cryptogenic cerebral ischemia. The sensitivity, specificity, and other indexes of C-TCD and C-TTE in the diagnosis of PFO-RLS were calculated using the Stata 16.0 software. The area under the summary receiver operating curve（SROC) was calculated. Results: Twenty-five 25 controlled studies involving a total of 2282 patients were analyzed. There was considerable heterogeneity between C-TCD and C-TTE sensitivity and specificity among the studies. The combined sensitivity and specificity of C-TCD and C-TTE were 0.95 (95%CI, 0.93-0.97) and 0.86(95%CI, 0.78-0.91), and 0.88 (95%CI, 0.69-0.96) and 0.99 (95%CI, 0.67-1.00). The positive likelihood ratio and negative likelihood ratio of C-TCD and C-TTE were 6.81 (95%CI, 4.42-10.48) and 0.05 (95%CI, 0.03-0.08), and 82.31(95%CI, 2.03-3341.00) and 0.12 (95%CI, 0.04-0.34). The areas under the SROC for C-TCD and C-TTE were 0.97 (95%CI, 0.95–0.98) and 0.98 (95%CI, 0.96–0.99), respectively, and were not significantly different by the Z test (z=-0.17, p=0.86). Conclusion: C-TCD and C-TTE have advantages in diagnosing PFO-RTL. The combination of C-TCD and C-TTE improves the detection rate and reduces the misdiagnosis rate. Key words: patent foramen ovale, cryptogenic cerebral ischemia, contrast-transthoracic echocardiography, contrast-transthoracic echocardiography

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