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Frontiers in Medicine 2021To evaluate the diagnostic accuracy of antineutrophil cytoplasmic antibody (ANCA) renal risk score (ARRS) for prediction of renal outcome in patients with...
To evaluate the diagnostic accuracy of antineutrophil cytoplasmic antibody (ANCA) renal risk score (ARRS) for prediction of renal outcome in patients with ANCA-associated glomerulonephritis (ANCA-GN). We searched PubMed, EMBASE, Ovid, Web of Science, the Cochrane Library, and ClinicalTrials.gov for studies, which used ARRS to predict end-stage renal disease (ESRD) in patients with ANCA-GN. Two reviewers independently screened articles for inclusion, assessed the quality of studies with both an adapted Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. We calculated the combined patients with ESRD in the ARRS categories and presented the summary and individual estimates based on the ARRS categories. Then, the sensitivity, specificity, diagnostic odds ratio (DOR), positive/negative likelihood ratio, and the area under the receiver operating characteristic (AUROC) curves of the pooled data for ARRS were used to assess the accuracy of the "above the low-risk threshold" (ARRS ≥ 2) and "high-risk grade" (ARRS ≥ 8) for renal outcome of patients with ANCA-GN. The hierarchical summary ROC (HSROC) was used to verify the accuracy value. The clinical utility of ARRS was evaluated by the Fagan plot. Heterogeneity was explored using meta-regression and subgroup analysis. A total of 12 distinct cohorts from 11 articles involving 1,568 patients with ANCA-GN were analyzed. The cumulative patients with ESRD at the maximum follow-up of 60 months was 5% (95% CI: 0.02-0.07; < 0.001) for ANCA-GN with low ARRS (0-1 points) and significantly increased to 22% (95% CI: 0.15-0.29; < 0.001) medium ARRS (2-7 points). The combined cumulative patients with ESRD was 59% (95% CI: 0.49-0.69; < 0.001) high ARRS (8-11 points). The pooled sensitivity of ARRS ≥ 2 in predicting ESRD was 98% with a specificity of 30% and a DOR of 15.08 and the mean AUROC value was 0.82. The pooled sensitivity of ARRS ≥ 8 in predicting ESRD was 58% with a specificity of 86% and a DOR of 7.59. The meta-regression and subgroup analysis indicated that variation in the geographic regions, study design, index risk, follow-up time, age of patient, publication year, and number of patient could be the potential sources of heterogeneity in the diagnosis of ARRS ≥ 8. This meta-analysis emphasized the good performance of the ARRS score in predicting the renal outcome in patients with ANCA-GN. However, these findings should be verified by future large-scale prospective studies.
PubMed: 35071256
DOI: 10.3389/fmed.2021.736754 -
Alimentary Pharmacology & Therapeutics Mar 2022There is growing support for a biopsy avoidant approach to diagnose coeliac disease in both children and adults, using a serological diagnosis instead. (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is growing support for a biopsy avoidant approach to diagnose coeliac disease in both children and adults, using a serological diagnosis instead.
AIMS
To assess the diagnostic accuracy of serological tests for coeliac disease in adults and children.
METHODS
Seven electronic databases were searched between January 1990 and August 2020. Eligible diagnostic studies evaluated the accuracy of serological tests for coeliac disease against duodenal biopsy. Risk of bias assessment was performed using QUADAS-2. Bivariate random-effects meta-analyses were used to estimate serology sensitivity and specificity at the most commonly reported thresholds.
RESULTS
113 studies (n = 28,338) were included, all in secondary care populations. A subset of studies were included in meta-analyses due to variations in diagnostic thresholds. Summary sensitivity and specificity of immunoglobulin A (IgA) anti-tissue transglutaminase were 90.7% (95% confidence interval: 87.3%, 93.2%) and 87.4% (84.4%, 90.0%) in adults (5 studies) and 97.7% (91.0%, 99.4%) and 70.2% (39.3%, 89.6%) in children (6 studies); and of IgA endomysial antibodies were 88.0% (75.2%, 94.7%) and 99.6% (92.3%, 100%) in adults (5 studies) and 94.5% (88.9%, 97.3%) and 93.8% (85.2%, 97.5%) in children (5 studies).
CONCLUSIONS
Anti-tissue transglutaminase sensitivity appears to be sufficient to rule out coeliac disease in children. The high specificity of endomysial antibody in adults supports its use to rule in coeliac disease. This evidence underpins the current development of clinical guidelines for a serological diagnosis of coeliac disease. Studies in primary care are needed to evaluate serological testing strategies in this setting.
Topics: Adult; Autoantibodies; Celiac Disease; Child; Humans; Immunoglobulin A; Protein Glutamine gamma Glutamyltransferase 2; Sensitivity and Specificity; Serologic Tests; Transglutaminases
PubMed: 35043426
DOI: 10.1111/apt.16729 -
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 -
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 -
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 -
Clinical Microbiology and Infection :... Jan 2022Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection commonly affecting immunocompromised people. Diagnosis usually requires invasive techniques to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection commonly affecting immunocompromised people. Diagnosis usually requires invasive techniques to obtain respiratory specimens. Minimally invasive detection tests have been proposed, but their operating characteristics are poorly described.
OBJECTIVES
To systematically review and meta-analyse the performance of minimally invasive PCP detection tests to inform diagnostic algorithms.
DATA SOURCES
Medline, Embase, Cochrane Library (inception to 15 October 2020).
STUDY ELIGIBILITY CRITERIA
Studies of minimally invasive PCP detection tests were included if they contained a minimum of ten PCP cases.
PARTICIPANTS
Adults at risk of PCP.
TESTS
Non-invasive PCP detection tests.
REFERENCE STANDARD
Diagnosis using the combination of clinical and radiographical features with invasive sampling.
ASSESSMENT OF RISK BIAS
Using the QUADAS-2 tool.
METHODS
We used bivariate and, when necessary, univariate analysis models to estimate diagnostic test sensitivity and specificity.
RESULTS
Fifty-two studies were included; most studies (40) comprised exclusively human immunodeficiency virus (HIV) -infected individuals; nine were mixed (HIV and non-HIV), two were non-HIV and one study did not report HIV status. Sampling sites included induced sputum, nasopharyngeal aspirate, oral wash and blood. The four testing modalities evaluated were cytological staining, fluorescent antibody, PCR and lactate dehydrogenase. Induced sputum had the most data available; this modality was both highly sensitive at 99% (95% CI 51%-100%) and specific at 96% (95% CI 88%-99%). Induced sputum cytological staining had moderate sensitivity at 50% (95% CI 39%-61%) and high specificity at 100% (95% CI 100%-100%), as did fluorescent antibody testing with sensitivity 74% (95% CI 62%-87%) and specificity 100% (95% CI 91%-100%).
CONCLUSION
There are several promising minimally invasive PCP diagnostic tests available, some of which may reduce the need for invasive respiratory sampling. Understanding the operating characteristics of these tests can augment current diagnostic strategies and help establish a more confident clinical diagnosis of PCP. Further studies in non-HIV infected populations are needed.
Topics: Adult; HIV Infections; Humans; Immunocompromised Host; Pneumocystis carinii; Pneumonia, Pneumocystis; Sensitivity and Specificity; Sputum
PubMed: 34464734
DOI: 10.1016/j.cmi.2021.08.017 -
Frontiers in Immunology 2021Despite the discovery that the human immunodeficiency virus 1 (HIV-1) is the pathogen of acquired immunodeficiency syndrome (AIDS) in 1983, there is still no effective...
Despite the discovery that the human immunodeficiency virus 1 (HIV-1) is the pathogen of acquired immunodeficiency syndrome (AIDS) in 1983, there is still no effective anti-HIV-1 vaccine. The major obstacle to the development of HIV-1 vaccine is the extreme diversity of viral genome sequences. Nonetheless, a number of broadly neutralizing antibodies (bNAbs) against HIV-1 have been made and identified in this area. Novel strategies based on using these bNAbs as an efficacious preventive and/or therapeutic intervention have been applied in clinical. In this review, we summarize the recent development of bNAbs and its application in HIV-1 acquisition prevention as well as discuss the innovative approaches being used to try to convey protection within individuals at risk and being treated for HIV-1 infection.
Topics: AIDS Vaccines; Animals; Antibody Specificity; Broadly Neutralizing Antibodies; Gene Transfer Techniques; Genes, env; Genetic Therapy; Genetic Variation; HIV Antibodies; HIV Infections; HIV-1; Humans; Immunity, Humoral; Immunization, Passive; Models, Immunological; Vaccine Development; env Gene Products, Human Immunodeficiency Virus
PubMed: 34354709
DOI: 10.3389/fimmu.2021.697683 -
Clinical Microbiology and Infection :... Sep 2021Appropriate laboratory diagnostics for emerging arboviruses are key for patient management, surveillance and intervention, including molecular tests and serological...
BACKGROUND
Appropriate laboratory diagnostics for emerging arboviruses are key for patient management, surveillance and intervention, including molecular tests and serological tests detecting viral antigen or virus-specific antibodies.
OBJECTIVES
We provide an overview of the challenges towards serological testing for the most important emerging arboviruses, including Zika, dengue and chikungunya viruses.
SOURCES
We retrieved a data set on performance of commercially available antibody- and antigen-detecting tests from 89 peer-reviewed articles conducting a systematic literature research in PubMed.
CONTENT
We identified commonly used antibody- and antigen-detecting tests and analysed their overall performance. We discuss how timing of serological testing and the use of paired samples from acute and convalescent phases of infection are crucial to optimize diagnostic sensitivity and specificity. We then exemplify how serological diagnostics are challenged by the patient's infection history through the 'original antigenic sin' and cross-reactive antibodies in the context of global co-circulation of antigenically related viruses. We highlight how individual infection histories with different arboviruses and with other pathogens such as herpes viruses and Plasmodia can produce inaccurate test results. We show that rapid tests for antibody and antigen detection in point-of-care settings have a significantly lower sensitivity compared with laboratory-based tests such as ELISA. We show that the performance of antibody- and antigen-detecting tests varies greatly between tropical regions of endemic transmission and non-endemic regions. Finally, we highlight that test sensitivity and specificity have to be equilibrated carefully and frequently either of them must be prioritized over the other, depending on disease prevalence and intended use of tests.
IMPLICATIONS
For reliable serological diagnostics, it is essential to be aware of inherent test limitations. Although multiplexed testing and testing of convalescence samples can improve diagnostic performance, global spread of (re-)emerging viruses requires careful implementation and evaluation of serological testing and unambiguous results may not always be achievable.
Topics: Antibodies, Viral; Antigens, Viral; Arbovirus Infections; Arboviruses; Humans; Sensitivity and Specificity; Serologic Tests
PubMed: 34111589
DOI: 10.1016/j.cmi.2021.05.047 -
Frontiers in Neuroscience 2021To review the available evidence on sensitivity and specificity of anti-NF155 antibody detection in diagnosing a specific subset of patients with chronic inflammatory...
To review the available evidence on sensitivity and specificity of anti-NF155 antibody detection in diagnosing a specific subset of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and to calculate the frequencies of different autoantibodies to paranodal proteins. Diagnosis of CIDP relies on clinical and neurophysiologic criteria and lacks useful diagnostic biomarkers. A subset of CIDP patients exhibit atypical clinical phenotypes and impaired response to conventional treatments. These patients were reported as having autoantibodies targeting paranodal protein neurofascin isoform 155 (NF155), contactin-1 (CNTN1), and contactin-associated protein-1 (CASPR1). Here, we conducted a meta-analysis to summarize evidence on the diagnostic and prognostic value of these autoantibodies, especially for anti-NF155 antibody. We searched the following electronic bibliographic databases: PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science. Eligible studies provided information to calculate the frequencies of anti-NF155 antibody and anti-CNTN1 antibody, the sensitivity and specificity of anti-NF155 antibody, and the incidence of improvement and deterioration among anti-NF155 antibody seropositive CIDP patients. Heterogeneity was assessed using Q and statistics. The pooled frequency of anti-NF155 autoantibody across 14 studies was 7% [95% confidence interval (CI): 0.05-0.10] with high heterogeneity; the overall pooled sensitivity and specificity of anti-NF155 antibody for the diagnosis of a specific subgroup of CIDP patients were 0.45 (95% CI: 0.29-0.63) and 0.93 (95% CI: 0.86-0.97), respectively. For diagnosing of a specific subset of CIDP characterized by poor response to intravenous immunoglobulin (IVIg), we found a moderate sensitivity and a high specificity. The anti-NF155 antibody test should be used as a confirmatory test rather than a screening test. PROSPERO, identifier: CRD42020203385 and CRD42020190789.
PubMed: 34108854
DOI: 10.3389/fnins.2021.637336 -
Pathogens (Basel, Switzerland) May 2021is the zoonotic parasite responsible for toxoplasmosis in warm-blooded vertebrates. This systematic review compares and evaluates the available knowledge on... (Review)
Review
is the zoonotic parasite responsible for toxoplasmosis in warm-blooded vertebrates. This systematic review compares and evaluates the available knowledge on enzyme-linked immunosorbent assays (ELISAs), their components, and performance in detecting antibodies in animals. Four databases were searched for published scientific studies on and ELISA, and 57 articles were included. Overall, indirect (95%) and in-house (67%) ELISAs were the most used types of test among the studies examined, but the 'ID Screen Toxoplasmosis Indirect Multi-species' was common among commercially available tests. Varying diagnostic performance (sensitivity and specificity) and Kappa agreements were observed depending on the type of sample (serum, meat juice, milk), antigen (native, recombinant, chimeric) and antibody-binding reagents used. Combinations of recombinant and chimeric antigens resulted in better performance than native or single recombinant antigens. Protein A/G appeared to be useful in detecting IgG antibodies in a wide range of animal species due to its non-species-specific binding. One study reported cross-reactivity, with and spp. This is the first systematic review to descriptively compare ELISAs for the detection of antibodies across different animal species.
PubMed: 34063342
DOI: 10.3390/pathogens10050605