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Biomolecules & Biomedicine Feb 2024Donor-derived cell-free DNA (dd-cfDNA) has emerged as a promising biomarker for detecting graft rejection. This study aimed to evaluate the diagnostic accuracy and... (Meta-Analysis)
Meta-Analysis
Donor-derived cell-free DNA (dd-cfDNA) has emerged as a promising biomarker for detecting graft rejection. This study aimed to evaluate the diagnostic accuracy and clinical value of applying it to kidney transplant rejection. Relevant literature on dd-cfDNA diagnostics in kidney transplant rejection was reviewed from PubMed, Embase, Cochrane Library, and Web of Science databases up to 2023. Data and study characteristics were extracted independently by two researchers, and disagreements were resolved through discussion. Diagnostic accuracy data for any rejection (AR) and antibody-mediated rejection (ABMR) were analyzed separately. Potential heterogeneity was analyzed by subgroup analysis or meta-regression. Funnel plots were used to clarify the presence or absence of publication bias. Nine publications provided data on dd-cfDNA accuracy in diagnosing patients with AR. The pooled sensitivity, specificity, and the area under the receiver operating characteristic (AUROC) curve with 95% confidence intervals (CI) were 0.59 (95% CI, 0.48-0.69), 0.83 (95% CI, 0.76-0.88), and 0.80 (95% CI, 0.76-0.83), respectively. Additionally, 12 studies focused on the diagnostic accuracy of dd-cfDNA for ABMR, showing pooled sensitivity, specificity, and the AUROC curve with 95% CI of 0.81 (95% CI, 0.72-0.88), 0.80 (95% CI, 0.73-0.86), and 0.87 (95% CI, 0.84-0.90), respectively. Study type, age group, and sample size contributed to heterogeneity. In summary, our findings indicate that while plasma dd-cfDNA accuracy in diagnosing patients with AR is limited by significant heterogeneity, it is a valuable biomarker for diagnosing ABMR.
PubMed: 38386614
DOI: 10.17305/bb.2024.10049 -
Translational Andrology and Urology Nov 2021To date, the results of studies into the effectiveness of positron emission tomography (PET) combined with computed tomography (CT) and bone scan (BS) in the diagnosis...
BACKGROUND
To date, the results of studies into the effectiveness of positron emission tomography (PET) combined with computed tomography (CT) and bone scan (BS) in the diagnosis of malignant prostate lesions have been inconsistent, and the advantages and disadvantages of the two methods cannot be accurately judged.
METHODS
Articles were retrieved from the China National Knowledge Infrastructure (CNKI) database, Wan Fang Medical Network, PubMed, Excerpta Medica data BASE (EMBASE), Medline, and Cochrane database. The keywords used in the search were: Ga-prostate specific membrane antibody (Ga-PSMA), PET/CT, prostate lesions, prostate adenocarcinoma, bone metastasis, and BS.
RESULTS
Ultimately, 3 publications were selected for inclusion in the meta-analysis. A total of 215 patients were considered in the 3 articles that met the inclusion criteria. All of the included articles were small sample studies, with sample sizes ranging from 28 to 113 cases. In this study, from the 3 randomized controlled trials, only 2 (66.67%) randomized controls described the correct randomized allocation method, and only 1 (33.33%) described the hidden allocation scheme in detail. The highest sensitivity for Ga-PSMA PET/CT was 0.96, with 95% CI: 0.87, 1.00, and the highest specificity was 1.00, with 95% CI: 0.96, 1.00. The highest sensitivity and specificity of BS were 0.92 with 95% CI: 0.81, 0.98 and 0.96 with 95% CI: 0.78, 1.00, respectively. The results of meta-analysis of Ga-PSMA PET/CT diagnosis with confirmation by surgical and histopathological examination showed that the area under the summary receiver operating characteristics (SROC) curve (AUC) =0.826 and standard error (SE) (AUC) =0.0425. The results of meta-analysis of BS diagnosis with confirmation by surgical and histopathological examination showed that the area under the SROC curve (AUC) =0.714 and SE (AUC) =0.0034.
DISCUSSION
The meta-analysis showed that Ga-PSMA PET/CT has clear advantages over BS in the diagnosis of bone metastases of malignant prostate tumors, and could improve the diagnostic accuracy of bone metastases.
PubMed: 34984188
DOI: 10.21037/tau-21-912 -
Clinics (Sao Paulo, Brazil) 2020Serologic testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) promises to assist in assessing exposure to and confirming the diagnosis of... (Meta-Analysis)
Meta-Analysis
Serologic testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) promises to assist in assessing exposure to and confirming the diagnosis of coronavirus disease 2019 (COVID-19), and to provide a roadmap for reopening countries worldwide. Considering this, a proper understanding of serologic-based diagnostic testing characteristics is critical. The aim of this study was to perform a structured systematic review and meta-analysis to evaluate the diagnostic characteristics of serological-based COVID-19 testing. Electronic searches were performed using Medline (PubMed), EMBASE, and Cochrane Library. Full-text observational studies that reported IgG or IgM diagnostic yield and used nucleic acid amplification tests (NAATs) of respiratory tract specimens, as a the reference standard in English language were included. A bivariate model was used to compute pooled sensitivity, specificity, positive/negative likelihood ratio (LR), diagnostic odds ratio (OR), and summary receiver operating characteristic curve (SROC) with corresponding 95% confidence intervals (CIs). Five studies (n=1,166 individual tests) met inclusion criteria. The pooled sensitivity, specificity, and diagnostic accuracy for IgG was 81% [(95% CI, 61-92);I2=95.28], 97% [(95% CI, 78-100);I2=97.80], and 93% (95% CI, 91-95), respectively. The sensitivity, specificity, and accuracy for IgM antibodies was 80% [(95% CI, 57-92);I2=94.63], 96% [(95% CI, 81-99);I2=92.96] and 95% (95% CI, 92-96). This meta-analysis demonstrates suboptimal sensitivity and specificity of serologic-based diagnostic testing for SARS-CoV-2 and suggests that antibody testing alone, in its current form, is unlikely to be an adequate solution to the difficulties posed by COVID-19 and in guiding future policy decisions regarding social distancing and reopening of the economy worldwide.
Topics: Antibodies, Viral; Betacoronavirus; COVID-19; COVID-19 Testing; Clinical Laboratory Techniques; Coronavirus Infections; Humans; Immunoglobulin G; Immunoglobulin M; Pandemics; Pneumonia, Viral; SARS-CoV-2; Sensitivity and Specificity; Serologic Tests
PubMed: 32785570
DOI: 10.6061/clinics/2020/e2212 -
Diagnostics (Basel, Switzerland) Sep 2021Anti-DFS70 antibodies have been proposed as a marker to exclude systemic autoimmune rheumatic disease (SARD). We conducted this systematic diagnostic test accuracy... (Review)
Review
Anti-DFS70 antibodies have been proposed as a marker to exclude systemic autoimmune rheumatic disease (SARD). We conducted this systematic diagnostic test accuracy review and meta-analysis to determine the performance of anti-DFS70 antibodies in patients with a positive anti-nuclear antibody (ANA) test result to exclude SARD. We searched PubMed, Embase, Web of Science, Scopus and the Cochrane Library up to 22 February 2021, and included studies examining the diagnostic accuracy of anti-DFS70 antibodies in patients with a positive ANA test result. The results were pooled using a hierarchical bivariate model and plotted in summary receiver operating characteristic curves. R software and Stata Statistical Software were used for the statistical analysis. Eight studies with 4168 patients were included. The summary sensitivity was 0.19 (95% confidence interval: 0.12-0.28) and the specificity was 0.93 (95% confidence interval: 0.88-0.96). The area under the curve was 0.69 (95% confidence interval: 0.64-0.72). The meta-regression analysis showed that targeting only ANA-associated rheumatic disease was associated with higher specificity. In addition, the studies with a non-SARD prevalence of <80% and using a chemiluminescence assay were associated with higher specificity. Anti-DFS70 antibodies have high specificity for the exclusion of SARD among patients presenting with a positive ANA test, but the sensitivity is low.
PubMed: 34573934
DOI: 10.3390/diagnostics11091592 -
Scientific Reports Dec 2020Recombinant monoclonal antibodies are used for treating various diseases, from asthma, rheumatoid arthritis, and inflammatory bowel disease to cancer. Although... (Meta-Analysis)
Meta-Analysis Review
Recombinant monoclonal antibodies are used for treating various diseases, from asthma, rheumatoid arthritis, and inflammatory bowel disease to cancer. Although monoclonal antibodies are known to have fewer toxic reactions compared with the conventional cytotoxic antineoplastic drugs, the cases of severe systemic hypersensitivity reaction (HSR) should be acknowledged. Our aim was to assess the diagnostic accuracy of the anti-IgE for galactose-α-1,3-galactose in patients with HSRs to cetuximab. We searched in PubMed, Cochrane Library, Scopus, and World of Science databases to July 1st, 2020. We included a total of 6 studies, with 1074 patients. Meta-analysis was performed using bivariate analysis and the random-effect model. The pooled sensitivity was 73% (95% CI 62-81%) and the pooled specificity was 88% (95% CI 79-94%). We had not found significant heterogeneity and, despite some discrepancies in the nature of data available in the analysed studies, we draw the conclusion that the presence of cetuximab specific IgE (anti cetuximab antibody) and/or galactose-α-1,3-galactose shows moderate to high sensitivity and specificity of developing an HSR. More studies are needed to establish a protocol necessary for the proper prediction and avoidance of HSR related to cetuximab.
Topics: Cetuximab; Galactose; Humans; Immunoglobulin E
PubMed: 33288791
DOI: 10.1038/s41598-020-78497-7 -
Carcinogenesis Apr 2022Clear cell ovarian cancer (CCOC) is a rare type of epithelial cancer often resistant to platinum-based chemotherapy. Biomarkers for the diagnosis of CCOC, and targets...
Clear cell ovarian cancer (CCOC) is a rare type of epithelial cancer often resistant to platinum-based chemotherapy. Biomarkers for the diagnosis of CCOC, and targets for immunotherapy, both have the potential to improve outcomes for patients. Our review aims to determine whether any antigens already identified in the literature could fulfil this remit. PubMed, Medline, Web of Science, Scopus, Cochrane, CINAHL and EMBASE were searched and included all reported studies up until August 2021. Primary research articles on human adult females including at least 10 CCOC patients were included. Quality assurance was carried out using a modified version of the QUADAS-2 tool. Sensitivity, specificity and area under the curve were extracted from each included study by two independent reviewers. Twenty-three articles were included which identified 19 gene transcripts/proteins and one antibody, with reported sensitivities between 21% and 100% and specificities between 0% and 100% for expression in CCOC and differentiation from other epithelial ovarian cancer subtypes, benign gynaecological disease or normal tissue. Twelve studies identified biomarkers with a sensitivity and specificity above 80%. A panel of biomarkers consisting of IMP3, napsin A and hepatocyte nuclear factor 1 beta achieved the highest area under the curve of 0.954. This review demonstrates that there are promising candidate biomarkers for the diagnosis of CCOC, some of which are highly specific, and have the potential to act as targets for therapy. However, larger cohort studies are needed to validate these biomarkers and their potential use in clinical practice.
Topics: Adult; Biomarkers; Carcinoma, Ovarian Epithelial; Female; Humans; Ovarian Neoplasms; Sensitivity and Specificity
PubMed: 35104328
DOI: 10.1093/carcin/bgac012 -
Frontiers in Physiology 2023In this comprehensive meta-analysis, our objective was to evaluate the diagnostic utility of graft-derived cell-free DNA (GcfDNA) in kidney allograft rejection and...
In this comprehensive meta-analysis, our objective was to evaluate the diagnostic utility of graft-derived cell-free DNA (GcfDNA) in kidney allograft rejection and explore associated factors. We conducted a thorough search of PubMed, Embase, and the Cochrane Library databases, spanning from their inception to September 2022. Statistical analysis was executed utilizing Stata 15, Meta-DiSc 1.4, and Review Manager 5.4 software. The combined pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the summary receiver operating characteristics (SROC) curve from the synthesis of findings across ten studies were as follows: 0.75 (0.67-0.81), 0.78 (0.72-0.83), 3.36 (2.89-4.35), 0.32 (0.24-0.44), 8.77 (4.34-17.74), and 0.83 (0.80-0.86), respectively. Among the ten studies primarily focused on GcfDNA's diagnostic potential for antibody-mediated rejection (ABMR), the optimal cut-off threshold demonstrated substantial diagnostic efficacy, with pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, DOR, and area under the summary receiver operating characteristics curve values of 0.83 (0.74-0.89), 0.75 (0.70-0.80), 3.37 (2.64-4.30), 0.23 (0.15-0.36), 14.65 (7.94-27.03), and 0.85 (0.82-0.88), respectively. These results underscore the high diagnostic accuracy of GcfDNA in detecting rejection. Furthermore, the optimal cut-off threshold proves effective in diagnosing ABMR, while a 1% threshold remains a robust diagnostic criterion for rejection. Notably, for ABMR diagnosis, droplet digital PCR digital droplet polymerase chain reaction emerges as a superior method in terms of accuracy when compared to other techniques. Nonetheless, further research is warranted to substantiate these findings.
PubMed: 38264334
DOI: 10.3389/fphys.2023.1293402 -
Journal of the American Board of Family... 2021The accuracy of individual symptoms, signs, and several easily obtainable hematologic parameters for diagnosing infectious mononucleosis (IM) still needs to be... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The accuracy of individual symptoms, signs, and several easily obtainable hematologic parameters for diagnosing infectious mononucleosis (IM) still needs to be confirmed. Improving the diagnosis of IM based on the clinical findings could prompt physicians to identify better which patients need a diagnostic test for IM. This study performed a systematic review to determine the accuracy of symptoms, signs, and hematologic parameters in patients with suspected IM that used heterophile antibody test or viral capsid antigen tests as the reference standard.
METHODS
The PubMed database was searched for all relevant articles. Two reviewers reviewed all studies in parallel and assessed the quality of the selected studies using the quality assessment of diagnostic accuracy studies 2 (QUADAS-2) criteria. The pooled measures of diagnostic performance were calculated by bivariate meta-analysis for each clinical finding, which included sensitivity, specificity, likelihood ratios, the diagnostic odds ratios, and the area under the receiver operating characteristic curve.
RESULTS
Seventeen studies were included in our final analysis. The prevalence of IM ranged from 2.1% to 80% among prospective cohort studies. The presence of splenomegaly (positive likelihood ratio [LR+], 2.39; 95% confidence interval [CI], 1.11-5.51), palatal petechiae (LR+, 1.32-11.40), posterior cervical lymphadenopathy (LR+, 3.16; 95% CI, 1.45-5.20), and axillary or inguinal cervical lymphadenopathy (LR+, 3.05; 95 CI, 1.85-4.70) were moderately useful for ruling in IM. The most helpful hematologic parameters for ruling in IM include lymphocytes greater than 4 × 10/L and greater than 40% to 50%, or atypical lymphocytes greater than 40%. A combination of lymphocytes greater than 50% and atypical lymphocytes greater than 10% (LR+, 50.40; 95% CI, 8.43-162) was also found to be helpful to rule in disease. Most of the clinical findings have limited diagnostic value in ruling out the disease when absent.
CONCLUSIONS
Although most symptoms and signs were unhelpful, the likelihood of IM is appreciably increased by several examination findings. Hematologic parameters were more accurate than symptoms and signs. Since most clinical findings have limited diagnostic value in ruling out the disease, physicians should not rely on the absence of any individual symptom or clinical sign for ruling out IM.
Topics: Diagnostic Tests, Routine; Humans; Infectious Mononucleosis; Neck; Prospective Studies; ROC Curve; Sensitivity and Specificity
PubMed: 34772769
DOI: 10.3122/jabfm.2021.06.210217 -
PLoS Neglected Tropical Diseases Sep 2023Diagnosis of arbovirus infection or exposure by antibody testing is becoming increasingly difficult due to global expansion of arboviruses, which induce antibodies that...
Diagnosis of arbovirus infection or exposure by antibody testing is becoming increasingly difficult due to global expansion of arboviruses, which induce antibodies that may (cross-)react in serological assays. We provide a systematic review of the current knowledge and knowledge gaps in differential arbovirus serology. The search included Medline, Embase and Web of Science databases and identified 911 publications which were reduced to 102 after exclusion of studies not providing data on possible cross-reactivity or studies that did not meet the inclusion criteria regarding confirmation of virus exposure of reference population sets. Using a scoring system to further assess quality of studies, we show that the majority of the selected papers (N = 102) provides insufficient detail to support conclusions on specificity of serological outcomes with regards to elucidating antibody cross-reactivity. Along with the lack of standardization of assays, metadata such as time of illness onset, vaccination, infection and travel history, age and specificity of serological methods were most frequently missing. Given the critical role of serology for diagnosis and surveillance of arbovirus infections, better standards for reporting, as well as the development of more (standardized) specific serological assays that allow discrimination between exposures to multiple different arboviruses, are a large global unmet need.
Topics: Humans; Arboviruses; Arbovirus Infections; Hematologic Tests
PubMed: 37738270
DOI: 10.1371/journal.pntd.0011651 -
PLoS Neglected Tropical Diseases Feb 2022Chikungunya virus (CHIKV) causes febrile illnesses and has always been misdiagnosed as other viral infections, such as dengue and Zika; thus, a laboratory test is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chikungunya virus (CHIKV) causes febrile illnesses and has always been misdiagnosed as other viral infections, such as dengue and Zika; thus, a laboratory test is needed. Serological tests are commonly used to diagnose CHIKV infection, but their accuracy is questionable due to varying degrees of reported sensitivities and specificities. Herein, we conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of serological tests currently available for CHIKV.
METHODOLOGY AND PRINCIPAL FINDINGS
A literature search was performed in PubMed, CINAHL Complete, and Scopus databases from the 1st December 2020 until 22nd April 2021. Studies reporting sensitivity and specificity of serological tests against CHIKV that used whole blood, serum, or plasma were included. QUADAS-2 tool was used to assess the risk of bias and applicability, while R software was used for statistical analyses. Thirty-five studies were included in this meta-analysis; 72 index test data were extracted and analysed. Rapid and ELISA-based antigen tests had a pooled sensitivity of 85.8% and 82.2%, respectively, and a pooled specificity of 96.1% and 96.0%, respectively. According to our meta-analysis, antigen detection tests serve as a good diagnostic test for acute-phase samples. The IgM detection tests had more than 90% diagnostic accuracy for ELISA-based tests, immunofluorescence assays, in-house developed tests, and samples collected after seven days of symptom onset. Conversely, low sensitivity was found for the IgM rapid test (42.3%), commercial test (78.6%), and for samples collected less than seven of symptom onset (26.2%). Although IgM antibodies start to develop on day 2 of CHIKV infection, our meta-analysis revealed that the IgM detection test is not recommended for acute-phase samples. The diagnostic performance of the IgG detection tests was more than 93% regardless of the test formats and whether the test was commercially available or developed in-house. The use of samples collected after seven days of symptom onset for the IgG detection test suggests that IgG antibodies can be detected in the convalescent-phase samples. Additionally, we evaluated commercial IgM and IgG tests for CHIKV and found that ELISA-based and IFA commercial tests manufactured by Euroimmun (Lübeck, Germany), Abcam (Cambridge, UK), and Inbios (Seattle, WA) had diagnostic accuracy of above 90%, which was similar to the manufacturers' claim.
CONCLUSION
Based on our meta-analysis, antigen or antibody-based serological tests can be used to diagnose CHIKV reliably, depending on the time of sample collection. The antigen detection tests serve as a good diagnostic test for samples collected during the acute phase (≤7 days post symptom onset) of CHIKV infection. Likewise, IgM and IgG detection tests can be used for samples collected in the convalescent phase (>7 days post symptom onset). In correlation to the clinical presentation of the patients, the combination of the IgM and IgG tests can differentiate recent and past infections.
Topics: Antigens, Viral; Chikungunya Fever; Chikungunya virus; Humans; Immunoglobulin G; Immunoglobulin M; Sensitivity and Specificity; Serologic Tests
PubMed: 35120141
DOI: 10.1371/journal.pntd.0010152