Predictive Performance of Placental Protein 13 for Screening Preeclampsia in the First Trimester: A Systematic Review and Meta-Analysis

Preeclampsia is a pregnancy-specific syndrome that affects maternal and neonatal mortality. Several serum biomarkers can be used to predict preeclampsia. Among these proteins, placental protein 13 (PP13) has received progressively more interest in recent studies. The decrease in PP13 expression is one of the earliest signs for the development of preeclampsia and has shown its predictive performance for preeclampsia. In this meta-analysis, we collected 17 observational studies with 40,474 pregnant women. The overall sensitivity of PP13 to predict preeclampsia was 0.62 [95% confidence interval (CI) = 0.49–0.74], the specificity was 0.84 (95%CI = 0.81–0.86), and the diagnostic odds ratio was nine (95%CI = 5–15). The area under the curve for summary receiver operating characteristic was 0.84. We then chose the early-onset preeclampsia as a subgroup. The sensitivity of early-onset subgroup was 0.63 (95%CI = 0.58–0.76), the specificity was 0.85 (95%CI = 0.82–0.88), and the diagnostic odds ratio was 10 (95%CI = 6–18). The findings of our meta-analysis indicate that PP13 may be an effective serum biomarker for the predictive screening of preeclampsia. Nonetheless, large prospective cohort studies and randomized controlled trials are expected to uncover its application in clinical practice. The heterogeneity of the original trials may limit the clinical application of PP13.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=188948 The meta-analysis was registered in PROSPERO (CRD42020188948).

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Prognostic Value of N-terminal Probrain Natriuretic Peptide for Patients with Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis

BioMed Research International ◽

10.1155/2020/3472615 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Qi Ni ◽

Chaoqian Li ◽

Hua Lin

Keyword(s):

Systematic Review ◽

Acute Respiratory Distress Syndrome ◽

Likelihood Ratio ◽

Odds Ratio ◽

Distress Syndrome ◽

Meta Analysis ◽

Positive Likelihood Ratio ◽

Negative Likelihood Ratio ◽

Diagnostic Odds Ratio ◽

Sensitivity Specificity

Objectives. The mortality rate of patients with acute respiratory distress syndrome (ARDS) is high. Hence, it is crucial to identify a reliable biomarker with wide clinical applications for predicting the prognosis of patients with ARDS. This systematic review and meta-analysis was conducted to investigate the value of plasma N-terminal probrain natriuretic peptide (NT-proBNP) for predicting mortality in patients with ARDS. Methods. An electronic search of databases including PubMed, Web of Science, Cochrane Library, and Chinese National Knowledge Infrastructure was conducted up to May 31, 2019, without language restrictions. The quality of the included studies was evaluated using QUADAS-2. Data were extracted and analyzed to obtain pooled estimates of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio. A forest graph was used to evaluate heterogeneity. Potential causes of heterogeneity were further explored by subgroup analysis based on the testing day, testing method, observation endpoint, or cut-off points. A summary receiver operating characteristic curve was drawn to obtain the pooled area under the curve. Results. A total of 7 studies involving 581 patients with ARDS were included. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were as follows: 0.79 (95% CI: 0.72–0.84), 0.79 (95% CI: 0.66–0.88), 3.68 (95% CI: 2.16–6.28), 0.27 (95% CI: 0.20–0.38), and 13.58 (95% CI: 6.17–29.90), respectively. The results of subgroup analysis showed that the testing day influenced the summary sensitivity and that the cut-off points influenced the summary sensitivity and specificity. Conclusion. Our results indicate that elevated plasma NT-proBNP levels have a moderate value for predicting the mortality of patients with ARDS.

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Accuracy of Ultrasound in Diagnosis of Pneumothorax: A Comparison between Neonates and Adults—A Systematic Review and Meta-Analysis

Canadian Respiratory Journal ◽

10.1155/2019/5271982 ◽

2019 ◽

Vol 2019 ◽

pp. 1-16 ◽

Cited By ~ 2

Author(s):

Hamid Dahmarde ◽

Fateme Parooie ◽

Morteza Salarzaei

Keyword(s):

Systematic Review ◽

Confidence Interval ◽

Odds Ratio ◽

English Language ◽

Meta Analysis ◽

Diagnostic Odds Ratio ◽

World Health ◽

Cochrane Library ◽

Chest Ultrasonography ◽

Link Type

Objective. The present systematic review and meta-analysis were conducted to investigate the accuracy of ultrasound in the diagnosis of pneumothorax in neonates and adults. Method. The searches were conducted by two independent researchers (MS and HD) to find the relevant studies published from 01/01/2009 until the end of 01/01/2019. We searched for published literature in the English language in MEDLINE via PubMed, Embase™ via ovid, the Cochrane Library, and Trip database. For literature published in other languages, we searched national databases (Magiran and SID), KoreaMed, and LILACS, and we searched OpenGrey (http://www.opengrey.eu/) and the World Health Organization Clinical Trials Registry (http://who.int/ictrp) for unpublished literature and ongoing studies. The keywords used in the search strategy were pneumothorax or ultrasound or chest ultrasonography or neonate or adult or aerothorax or sensitivity or specificity or diagnostic accuracy. The list of previous study resources and systematic reviews was also searched for identifying the published studies (MS and HD). Analyses were performed using Meta-Disc 1.4. Results. In total, 1,565 patients (255 neonates, 1212 adults, and 101 pediatrics suspected of pneumothorax) were investigated in 10 studies. The overall specificity of chest ultrasound in the diagnosis of pneumothorax in both populations of adults and neonates was 85.1% at the confidence interval of 95 percent (95% CI 81.1%–88.5%). At the confidence interval of 95 percent, the sensitivity was 98.6% (95% CI 97.7%–99.2%). The diagnostic odds ratio was 387.72 (95% CI 76.204–1972.7). For the diagnosis of pneumothorax in neonates, the ultrasound sensitivity was 96.7% at the confidence interval of 95 percent (95% CI 88.3%–99.6%). At the confidence interval of 95 percent, the specificity was 100% (95% CI 97.7%–100%). For the diagnosis of pneumothorax in adults, the ultrasound sensitivity was 82.9% at the confidence interval of 95 percent (95% CI 78.3–86.9%). At the confidence interval of 95 percent, the specificity was 98.2% (95% CI 97.0%–99.0%). The diagnostic odds ratio was 423.13 (95% CI 45.222–3959.1). Analyzing studies indicated that the sensitivity of “absence lung sliding” sign for the diagnosis of pneumothorax was 87.2% (95% CI 77.7–93.7), and specificity was 99.4% (95% CI 96.5%–100%). DOR was 556.74 (95% CI 100.03–3098.7). The sensitivity of “lung point” sign for the diagnosis of pneumothorax was 82.1% (95% CI 71.7%–89.8%), and the specificity was 100% (at the confidence interval of 95% CI 97.6%–100%). DOR was 298.0 (95% CI 58.893–1507.8). Conclusion. The diagnosis of pneumothorax using ultrasound is accurate and reliable; additionally, it can result in timely diagnoses specifically in neonatal pneumothorax. Using this method facilitates the therapy process; lack of ionizing radiation and easy operation are benefits of this imaging technique.

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The diagnostic accuracy of B-mode ultrasound in detecting meniscal tears: a systematic review and pooled meta-analysis

Medical Ultrasonography ◽

10.11152/mu-1252 ◽

2018 ◽

Vol 20 (2) ◽

pp. 164 ◽

Cited By ~ 3

Author(s):

Fajin Dong ◽

Lei Zhang ◽

Shuxia Wang ◽

Duo Dong ◽

Jinfeng Xu ◽

...

Keyword(s):

Systematic Review ◽

Diagnostic Accuracy ◽

Likelihood Ratio ◽

Odds Ratio ◽

Meta Analysis ◽

Diagnostic Odds Ratio ◽

Cochrane Library ◽

Meniscal Tears ◽

Linear Probe ◽

Sensitivity Specificity

Aim: To evaluate the diagnostic accuracy of meniscal tears using B-mode ultrasound and high-frequency linear probe by conducting a systematic review and pooled meta-analysis. Material and methods: The Cochrane library, Embase, and Pubmed were searched for relevant studies up to 29 July 2017. The arthroscopy was used as the reference standard. The results were estimated by pooled sensitivity, specificity, diagnostic odds ratio, likelihood ratio, and the area under the summary receiver operating characteristic (SROC). Results: Seven prospective studies met the selection criteria, comprising 321meniscal tears from 472 patients. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the SROC curve were 88.80% (95%CI: 82.83-92.87), 84.66% (95%CI: 75.89-90.64), 5.79(95%CI: 3.66-9.15), 0.13 (95%CI: 0.09-0.20), and 43.74 (95%CI: 24.01-79.68), respectively. The area under the SROC curve was 93% (95%CI: 91-95). Conclusions: This meta-analysis indicates that 2-dimensional ultrasound is useful, and could be routinely used for estimating meniscal injuries in the human knee joint

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Vasculogenic mimicry as a poor diagnostic and prognostic indicator in patients with malignant‎ melanoma: A ‎systematic review and meta-analysis

10.21203/rs.2.11912/v1 ◽

2019 ◽

Author(s):

Zhenhua Zhang ◽

Saber Imani ◽

Marzieh Dehghan Shasaltaneh ◽

Hossein Hosseinifard ◽

Zou Linglin ◽

...

Keyword(s):

Systematic Review ◽

Likelihood Ratio ◽

Meta Analysis ◽

Vasculogenic Mimicry ◽

Positive Likelihood Ratio ◽

Negative Likelihood Ratio ◽

Prognostic Indicator ◽

Diagnostic Odds Ratio ◽

P Value ◽

Summary Receiver Operating Characteristic

Abstract Background Vasculogenic mimicry (VM), a brand-new tumor microvascular model of non-endothelial cells, is proposed as an important therapeutic target in malignant melanoma (MM). We performed a systematic review to evaluate the diagnostic and prognostics accuracy of VM for overall survival of MM patients. Methods The quality of the included studies was assessed by QUADAS-2 tool. Diagnostic capacity of VM variables were pooled by the Meta-Disc software in term of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic (SROC). Results A retrospective observational study was conducted based on ‎ten studies including 978 clinically melanoma patients with proportion (P). VM+ melanoma cells are associated with poor prognosis in 38% of MM group (P = 0.35, 95% confidence intervals (CI): 0.27-0.42, P-value < 0.001). The pooled sensitivity and specificity were 0.82 (95% CI: 0.79-0.84) and 0.69 (95% CI: 0.66-0.71), respectively. Furthermore, the pooled PLR, NLR, and DOR were 2.56 (95% CI: 1.94-3.93), 0.17 (95% CI: 0.07-0.42), and 17.75 (95% CI: 5.30-59.44), respectively. Also, the AUC of SROC was 0.63, indicating the highly conserving of VM as a biomarker‎. Importantly, subgroup results suggested that VM+ tumor was significantly accurate prognostics biomarkers when diagnosed by CD31-/PAS+ staining methods in Asian MM samples (P-value > 0.001). Conclusions Our finding supports the VM+ tumor as a promising prognostic biomarker and effective adjuvant therapeutic strategy in prognostics of Asian MM patients.

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Effects of thymectomy on late-onset non-thymomatous myasthenia gravis: systematic review and meta-analysis

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-021-01860-y ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Jinwei Zhang ◽

Yuan Chen ◽

Hui Zhang ◽

Zhaoyu Yang ◽

Peng Zhang

Keyword(s):

Systematic Review ◽

Conservative Treatment ◽

Myasthenia Gravis ◽

Early Onset ◽

Odds Ratio ◽

Late Onset ◽

Meta Analysis ◽

Therapeutic Strategies ◽

Cochrane Library ◽

Study Objective

Abstract Background The effects of thymectomy on late-onset non-thymomatous myasthenia gravis (NTMG) remain controversial. The objective of this study was to conduct a systematic review in order to answer two questions pertinent to late-onset NTMG: (1) do patients with late-onset NTMG experience the same effects from thymectomy as their early-onset counterparts? (2) Compared with conservative treatment, does thymectomy have any benefits for late-onset NTMG patients? Methods We searched the PubMed, EMBASE, and Cochrane Library databases for studies published from January 1, 1950 to March 10, 2021. Outcomes were measured via clinical stable remission/pharmacological remission (CSR/PR) and improvement rates. We used Stata software to analyze the data. Results We ultimately included a total of 12 observational articles representing the best evidence answering the questions of our study objective. Of these, nine studies, which included 896 patients overall (766 early-onset and 230 late-onset), compared postoperative outcomes between early- and late-onset NTMG. The remaining three articles, which included 216 patients (75 in the thymectomy group and 141 in the conservative-treatment group), compared thymectomy with conservative treatment for late-onset NTMG. The early- versus late-onset NTMG studies demonstrated that patients in the former category were 1.95× likelier than their late-onset counterparts to achieve clinical remission (odds ratio [OR] 1.95; 95% confidence interval [CI] 1.39–2.73; I2 = 0%). No difference was seen in improvement or remission + improvement rates between these two groups. When comparing thymectomy with conservative treatments in late-onset NTMG patients, neither did we observe any difference in CSR/PR. Conclusion We found that late-onset NTMG patients had a lower chance of achieving CSR after thymectomy than early-onset patients. Thymectomy in late-onset NTMG also yielded no benefit to CSR or PR compared with conservative treatments. In late-onset NTMG patients, thymectomy should therefore be performed with caution, and the appropriate cutoff between early- and late-onset MG should be further explored in order to tailor and execute the proper therapeutic strategies.

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Accuracy of Enzyme-Linked Immunosorbent Assays (ELISAs) in Detecting Antibodies againstMycobacterium lepraein Leprosy Patients: A Systematic Review and Meta-Analysis

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2018/9828023 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 5

Author(s):

Omar Ariel Espinosa ◽

Silvana Margarida Benevides Ferreira ◽

Fabiana Gulin Longhi Palacio ◽

Denise da Costa Boamorte Cortela ◽

Eliane Ignotti

Keyword(s):

Diagnostic Accuracy ◽

Odds Ratio ◽

Meta Analysis ◽

Characteristic Curve ◽

Diagnostic Odds Ratio ◽

Cochrane Library ◽

Likelihood Ratios ◽

Summary Receiver Operating Characteristic ◽

Immunosorbent Assays ◽

Sensitivity Specificity

IgM againstMycobacterium lepraemay be detected by enzyme-linked immunosorbent assays (ELISAs) based on phenolic glycolipid I (PGL-I) or natural disaccharide octyl bovine serum albumin (ND-O-BSA) as antigens, and the IgG response can be detected by an ELISA based on lipid droplet protein 1 (LID-1). The titers of antibodies against these antigens vary with operational classification. The aim of this study was to compare the accuracy of ELISAs involving PGL-I and ND-O-BSA with that involving LID-1. We included studies that analyze multibacillary and paucibacillary leprosy cases and evaluate the diagnostic accuracy of ELISAs based on LID-1 and/or PGL-I or ND-O-BSA as antigens to measure antibody titers againstM. leprae. Studies were found via PubMed, the Virtual Health Library Regional Portal, Literatura Latino-Americana e do Caribe em Ciências da Saúde, Índice Bibliográfico Espanhol de Ciências de Saúde, the Brazilian Society of Dermatology, National Institute for Health and Clinical Excellence, Cochrane Library, Embase (the Elsevier database), and Cumulative Index to Nursing and Allied Health Literature. The Quality Assessment of Diagnostic Accuracy Studies served as a methodological validity tool. Quantitative data were extracted using the Standards for Reporting of Diagnostic Accuracy. Sensitivity, specificity, and a diagnostic odds ratio were calculated, and a hierarchical summary receiver-operating characteristic curve and forest plots were constructed. The protocol register code for this meta-analysis is PROSPERO 2017: CRD42017055983. Nineteen studies were included. ND-O-BSA showed better overall performance in terms of sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio when compared with PGL-I and LID-1. The multibacillary group showed better performance on these parameters (than the paucibacillary group did), at 94%, 99%, 129, 0.05, and 2293, respectively. LID-1 did not provide any advantage regarding the overall estimate of sensitivity in comparison with PGL-I or ND-O-BSA.

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Autoantibodies as biomarkers for colorectal cancer: A systematic review, meta-analysis, and bioinformatics analysis

The International Journal of Biological Markers ◽

10.1177/1724600819880906 ◽

2019 ◽

Vol 34 (4) ◽

pp. 334-347 ◽

Cited By ~ 3

Author(s):

Hejing Wang ◽

Xiaojin Li ◽

Donghu Zhou ◽

Jian Huang

Keyword(s):

Colorectal Cancer ◽

Protein Interactions ◽

Odds Ratio ◽

Bioinformatics Analysis ◽

Early Stage ◽

Meta Analysis ◽

Cyclin B1 ◽

Diagnostic Odds Ratio ◽

Summary Receiver Operating Characteristic ◽

Bioinformatics Analyses

Colorectal cancer is a very common cancer worldwide. Serum tumor-associated autoantibodies (TAAbs), especially the anti-p53 autoantibody, may be promising biomarkers to detect early-stage colorectal cancer. This study aimed to identify all known autoantibodies and their value in colorectal cancer diagnosis, as well as exploring the underlying connections and mechanisms through a bioinformatics analysis. Databases were used to select available articles of TAAbs in colorectal cancer. In a meta-analysis of the anti-p53 autoantibody, the diagnostic odds ratio and area under the curve (AUC) of the summary receiver-operating characteristic (SROC) curve were calculated using Stata 12.0 and Meta-Disc 1.4. We identified 73 articles including 199 single autoantibodies and 42 multiple autoantibodies. The maximum value of Youden’s index was 0.76, combining c-MYC, p53, cyclin B1, p62, Koc, IMP1, and survivin. The diagnostic odds ratio for anti-p53 autoantibody at all stages was 10.86 (95% CI 8.40, 14.06) with low heterogeneity (I2 = 40.3%) and the AUC of the SROC curve was 0.82. For the anti-p53 autoantibody in early-stage colorectal cancer, the diagnostic odds ratio was 4.82 (95% CI 2.95, 7.87) with heterogeneity (I2 = 7.9%) and the AUC of the SROC curve was 0.72. Eighty-seven autoantibodies were selected for bioinformatics analyses. We found that the most enriched functional terms and protein–protein interactions may relate to the mechanism of autoantibody generation. In summary, our study summarized the diagnostic value of TAAbs in colorectal cancer, either as single molecules or in combination. Bioinformatics analyses may be a new approach to explore the mechanism of autoantibody generation.

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Fecal fusobacterium nucleatum for detecting colorectal cancer: a systematic review and meta-analysis

The International Journal of Biological Markers ◽

10.1177/1724600818781301 ◽

2018 ◽

Vol 33 (4) ◽

pp. 345-352 ◽

Cited By ~ 4

Author(s):

Qian Huang ◽

Yonghai Peng ◽

Fangwei Xie

Keyword(s):

Colorectal Cancer ◽

Systematic Review ◽

Likelihood Ratio ◽

Odds Ratio ◽

Meta Analysis ◽

Area Under The Curve ◽

Positive Likelihood Ratio ◽

Negative Likelihood Ratio ◽

Fusobacterium Nucleatum ◽

Diagnostic Odds Ratio

Objective: The purpose of this systematic review and meta-analysis was to evaluate the efficacy of fecal Fusobacterium nucleatum ( Fn) for detecting colorectal cancer. It is the first systematic review and meta-analysis to focus exclusively on fecal Fn for colorectal cancer. Materials and methods: Comprehensive searches of several databases before January 2018 were conducted. Fecal Fn for detecting colorectal cancer was evaluated via pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the curve. Heterogeneity was explored using meta-regression and subgroup analyses. The publication bias and the overall quality of evidence were also analyzed. Results: Our analysis included six papers containing seven case-control studies in the systematic review and meta-analysis. Overall sensitivity and specificity were 0.68 (95% confidence interval (CI) 0.64, 0.72) and 0.78 (95% CI 0.75, 0.81), respectively. The positive likelihood ratio and negative likelihood ratio in detecting colorectal cancer were 2.87 (95% CI 1.62, 5.10) and 0.40 (95% CI 0.30, 0.54) respectively. The diagnostic odds ratio (OR) was 8.75 (95% CI 4.86, 15.78) and the area under the curve was 0.80. A subgroup analysis showed that in Asia, the colorectal cancer sample size ⩾50 had higher specificity (specificity 0.85, 95% CI 0.80, 0.88). No publication bias existed. The GRADEpro showed a moderate level of the available evidence. Conclusions: Compared to other examinations, the fecal Fn test seems a good choice for detecting colorectal cancer. It also has better diagnostic performance in Asians. However, more clinical trials with large sample sizes and strict randomization are needed to further verify the evidence.

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Predictive Value of HE4 in Platinum-Based Chemotherapy for Ovarian Cancer: A Systematic Review

Frontiers in Oncology ◽

10.3389/fonc.2021.703949 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yue Han ◽

Lili Jiang ◽

Kuiran Liu ◽

Ling Ouyang ◽

Yan Li

Keyword(s):

Systematic Review ◽

Ovarian Cancer ◽

Sensitivity And Specificity ◽

Odds Ratio ◽

Meta Analysis ◽

Diagnostic Odds Ratio ◽

The Third ◽

Preoperative Serum ◽

Platinum Based Chemotherapy ◽

Platinum Chemotherapy

ObjectiveTo evaluate the value of serum Human epididymis protein 4 (HE4) for predicting the resistance of ovarian cancer (OS) to platinum chemotherapy.MethodWe searched the MEDLINE (PubMed), EMBASE, Cochrane Central, Web of Science, SCOPUS, and CNKI databases and screened all studies evaluating serum HE4 for predicting OC resistance to treatment with platinum. Two researchers independently evaluated the quality of all eligible original studies using QUADAS-2. RevMan 5.4 was used to compile the quality evaluation form. We also performed a meta-analysis with STATA15.1, and Deek’s funnel plots were used to detect any publication bias.ResultsEight studies were included in the final meta-analysis. Our results showed that the sensitivity and specificity of preoperative serum HE4 in predicting the resistance of OC to platinum chemotherapy was 80% and 67%, respectively. The diagnostic odds ratio was 8, and the AUC was 0.78 (95% CI: 0.75-0.82), whereas the pooled sensitivity and specificity of serum HE4 after the third-cycle of chemotherapies for predicting chemoresistance in OC was 86% and 85%, respectively, with a diagnostic odds ratio of 33 and AUC = 0.92 (95% CI: 0.89 – 0.94).ConclusionHE4 may be an effective predictor of platinum-based chemotherapeutic resistance of OC. Serum HE4 levels after the third chemotherapy cycle may be indicative for clinical practice. Further research is needed to validate the significance of HE4 in the long-term management of OC.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, PROSPERO (CRD42021220099).

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Mycobacterial heparin-binding hemagglutinin (HBHA)-induced interferon-γ release assay (IGRA) for discrimination of latent and active tuberculosis: A systematic review and meta-analysis

PLoS ONE ◽

10.1371/journal.pone.0254571 ◽

2021 ◽

Vol 16 (7) ◽

pp. e0254571

Author(s):

Jinhua Tang ◽

Yuan Huang ◽

Zheng Cai ◽

Yueyun Ma

Keyword(s):

Systematic Review ◽

Likelihood Ratio ◽

Odds Ratio ◽

Selection Criteria ◽

Meta Analysis ◽

Diagnostic Odds Ratio ◽

Interferon Γ ◽

Active Tuberculosis ◽

Heparin Binding ◽

Release Assay

Background The Mycobacterial heparin-binding hemagglutinin (HBHA) is an important latency-associated antigen that can be used to distinguish between latent tuberculosis infection (LTBI) and active tuberculosis (ATB). Although many studies were explored the efficiency of the HBHA-induced interferon-γ release assay (IGRA) in different populations, the clinical differential value of HBHA-IGRA is still controversial. Therefore, the aim of this study was to determine whether the HBHA-IGRA can be used as an efficient test for the discrimination of LTBI and ATB by a systematic review and meta-analysis. Methods Relevant articles were retrieved from PubMed, Embase, Web of Science, and the Cochrane Library on Oct 18, 2020, with no start date limitation. The quality of each study was evaluated using Review Manager 5.4. The Stata MP v.14.0 software was used to combine sensitivity, specificity, likelihood ratio (LR), diagnostic odds ratio (DOR), summary receiver operating characteristic (SROC) curve, and area under SROC (AUC) to evaluate the diagnostic value of HBHA-IGRA for discrimination of LTBI and ATB. Meta-regression and subgroup analysis were performed for the sources of heterogeneity based on the selection criteria for active TB, the population, the TB burden, the type of antigen, the type of sample, and the time of antigen stimulation. Results A total of 13 studies (14 results) were included in this meta-analysis, including 603 ATB patients and 514 LTBI individuals. The pooled sensitivity and specificity of the HBHA-IGRA for discrimination of the LTBI and ATB were 0.70 (95% CI, 0.57~0.80) and 0.78 (95% CI, 0.71~0.84), respectively. The pooled positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 3.15 (95%CI, 2.43~4.09), 0.39 (95% CI, 0.27~0.56), and 8.11 (95% CI, 4.81~13.67), respectively. The AUC was 0.81 (95% CI, 0.77~0.84). The subgroup analysis showed that the main source of heterogeneity was due to the HIV-infected population incorporated, and the different selection criteria of active TB subjects would also lead to the variation of the pooled sensitivity and specificity. Different TB burdens, HBHA antigen types, sample types, antigen stimulation time and BCG vaccination did not affect the heterogeneity in this analysis. Conclusion The HBHA-IGRA is a promising immunodiagnostic test for discrimination of latent and active TB, which can be added in commercial IGRAs to enhance the differential diagnostic performance.

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