Diagnostic Accuracy of Lipopolysaccharide-Binding Protein as Biomarker for Sepsis in Adult Patients: A Systematic Review and Meta-Analysis

IntroductionLipopolysaccharide-binding protein (LBP) is widely reported as a biomarker to differentiate infected from non-infected patients. The diagnostic use of LBP for sepsis remains a matter of debate. We aimed to perform a systematic review and meta-analysis to assess the diagnostic accuracy of serum LBP for sepsis in adult patients.MethodsWe performed a systematic review and meta-analysis to assess the accuracy of LBP for sepsis diagnosis. A systematic search in PubMed and EMBASE for studies that evaluated the diagnostic role of LBP for sepsis through December 2015 was conducted. We searched these databases for original, English language, research articles that studied the diagnostic accuracy between septic and non-septic adult patients. Sensitivity, specificity, and other measures of accuracy, such as diagnostic odds ratio (DOR) and area under the receiver operating characteristic curve (AUC) of LBP were pooled using the Hierarchical Summary Receiver Operating Characteristic (HSROC) method.ResultsOur search returned 53 reports, of which 8 fulfilled the inclusion criteria, accounting for 1684 patients. The pooled sensitivity and specificity of LBP for diagnosis of sepsis by the HSROC method were 0.64 (95% CI: 0.56–0.72) and 0.63 (95% CI: 0.53–0.73), respectively. The value of the DOR was 3.0 (95% CI: 2.0–4.0) and the AUC was 0.68 (95% CI: 0.64–0.72). Meta-regression analysis revealed that cut-off values accounted for the heterogeneity of sensitivity and sample size (> = 150) accounted for the heterogeneity of specificity.ConclusionsBased on the results of our meta-analysis, LBP had weak sensitivity and specificity in the detection of sepsis. LBP may not be practically recommended for clinical utilization as a single biomarker.     

Should We Use Prolactin Adjustment in Bilateral Inferior Petrosal Sinus Sampling to Diagnose Cushing Disease? A Joint Meta-Analysis of Head-to-Head Diagnostic Tests Accuracy Studies

ObjectivePrevious studies have shown inconsistent results regarding the usefulness of prolactin adjustment in bilateral inferior petrosal sinus sampling (BIPSS) in the differential diagnosis of adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome (CS). This meta-analysis compared the diagnostic accuracy of prolactin adjustment versus no adjustment in BIPSS.MethodsThis study searched the PubMed, Embase, Web of Science, Cochrane library, and WanFang databases for published data as of March 2022 on the use of prolactin adjustment in BIPSS to differentially diagnose ACTH-dependent CS. A Bayesian joint bivariate model was used in the head-to-head comparison of the diagnostic accuracy.ResultsThis meta-analysis included a total of 10 studies with 300 patients. The combined sensitivity and specificity for BIPSS without prolactin adjustment were 94.47% (95% CI, 88.67%-98.44%) and 91.14% (95% CI, 57.17%-99.80%), respectively. The combined sensitivity and specificity after prolactin adjustment were 99.97% (95% CI, 99.03%-100.00%) and 80.69% (95% CI, 50.27%-97.82%), respectively. After the prolactin adjustment, the sensitivity of BIPSS to diagnose Cushing disease was improved with a statistically significant difference (difference in sensitivity, 5.39%; 95% CI, 1.37%-11.26%), whereas the decrease in specificity was without a statistically significant difference (difference in specificity, −9.20%; 95% CI, −42.02% to 26.61%).ConclusionThis meta-analysis indicated that prolactin adjustment in BIPSS might help to recognize Cushing disease among patient with ACTH-dependent CS. However, prolactin adjustment may not help identify ectopic ACTH syndrome in BIPSS.     

Spleen Stiffness Is Superior to Liver Stiffness for Predicting Esophageal Varices in Chronic Liver Disease: A Meta-Analysis

MethodsPubmed/Medline, Embase, Cochrane Library and Ovid were searched for all studies assessing SS and LS simultaneously in EV diagnosis. A total of 16 studies including 1892 patients were included in this meta-analysis, and the pooled statistical parameters were calculated using the bivariate mixed effects models.ResultsIn detection of any EV, for LS measurement, the summary sensitivity was 0.83 (95% confidence interval [CI]: 0.78–0.87), and the specificity was 0.66 (95% CI: 0.60–0.72). While for SS measurement, the pooled sensitivity and specificity was 0.88 (95% CI: 0.83–0.92) and 0.78 (95% CI: 0.73–0.83). The summary receiver operating characteristic (SROC) curve values of LS and SS were 0.81 (95% CI: 0.77–0.84) and 0.88 (95% CI: 0.85–0.91) respectively, and the results had statistical significance (P<0.01). The diagnostic odds ratio (DOR) of SS (25.73) was significantly higher than that of LS (9.54), with the relative DOR value was 2.48 (95%CI: 1.10–5.60), P<0.05.ConclusionsUnder current techniques, SS is significantly superior to LS for identifying the presence of EV in patients with CLD. SS measurement may help to select patients for endoscopic screening.     

Role of Transthoracic Lung Ultrasonography in the Diagnosis of Pulmonary Embolism: A Systematic Review and Meta-Analysis

Background

Pulmonary embolism (PE) is a potentially life-threatening condition. Although computed tomography pulmonary angiography (CTPA) is the reference standard for diagnosis, its early diagnosis remains a challenge, and the concerns about the radiation exposures further limit the general use of CTPA. The primary aim of this meta-analysis was to evaluate the overall diagnostic accuracy of transthoracic lung ultrasound (TLS) in the diagnosis of PE.

Methods

PubMed, Web of science, OvidSP, ProQuest, EBSCO, Cochrane Library and Clinicaltrial.gov were searched systematically. The quality of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and hierarchical summary receiver operating characteristic (HSROC) curves were used to examine the TS performance. The Bayes analysis was used to calculate the post-test probability of PE. Publication bias was assessed with Deeks funnel plot.

Results

The results indicated that the sensitivity, specificity, PLR and NLR were 0.85 (95% confidence interval (CI), 0.78 to 0.90), and 0.83 (95% CI, 0.73 to 0.90). And the DOR and HSROC were 28.82 (95% CI, 17.60 to 47.21), 0.91(95% CI, 0.88, 0.93).

Conclusions

The present meta-analysis suggested that transthoracic lung ultrasonography is helpful in diagnosing pulmonary embolism. Although the application of transthoracic lung ultrasound may change some patients’ diagnostic processes, it is inappropriate to generally use transthoracic ultrasonography in diagnosing pulmonary embolism currently.     

Diagnostic value of GLUT-1 in distinguishing malignant mesothelioma from reactive mesothelial cells: a meta-analysis

Abstract

Background: Previous studies have demonstrated the diagnostic value of glucose transporter 1 (GLUT-1) to distinguish malignant mesothelioma (MM) from reactive mesothelial cells (RMC), but the results are inconsistent. The purpose of this meta-analysis is to investigate the diagnostic accuracy of GLUT-1 in distinguishing MM from RMC.

Methods: A systematical search was conducted until May 2019 in PubMed, Medline, Embase and the Cochrane Library. The revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2) was used to assess the quality of the eligible studies. The Stata15 and Review Manager5.3 software programmes were used to perform the meta-analysis.

Results: A total of 24 studies, including 969?MM patients and 1080 RMC individuals were explored in the meta-analysis. The summary assessments revealed that the pooled sensitivity was 0.73 (95% CI, 0.62–0.81) and the pooled specificity was 0.95 (95% CI, 0.91–0.98). The area under the summary ROC curve (AUC) was 0.93 (95% CI: 0.91–0.95).

Conclusions: GLUT-1 is highly accurate to distinguish MM from RMC.     

Meta-Analysis of Gadoxetic Acid Disodium (Gd-EOB-DTPA)-Enhanced Magnetic Resonance Imaging for the Detection of Liver Metastases

Objective

To determine the accuracy of MR imaging with Gd-EOB-DTPA for the detection of liver metastases.

Materials and Methods

PUBMED, EMBASE, the Web of Science, and the Cochrane Library were searched for original articles published prior to February 2012. The criteria for the inclusion of articles were as follows: reported in the English language; MR imaging with Gd-EOB-DTPA was performed to detect liver metastases; histopathologic analysis (surgery, biopsy), intraoperative observation (manual palpatation, intraoperative ultrasonography), and/or follow-up US was the reference standard; and data were sufficient for the calculation of true-positive or false-negative values. The methodological quality was assessed by using the quality assessment of diagnostic studies instrument. The data were extracted to calculate sensitivity, specificity, predictive value, diagnostic odds ratio, and areas under hierarchical summary receiver operating characteristic (HSROC) curve to perform heterogeneity test and threshold effect test, as well as publication bias analysis and subgroup analyses.

Results

From 229 citations, 13 were included in the meta-analysis with a total of 1900 lesions. We detected heterogeneity between studies and evidence of publication bias. The methodological quality was moderate. The pooled weighted sensitivity with a corresponding 95% confidence interval (CI) was 0.93 (95% CI: 0.90, 0. 95), the specificity was 0.95 (95% CI: 0.91, 0.97), the positive likelihood ratio was 18.07 (95% CI: 10.52, 31.04), the negative likelihood ratio was 0.07 (95% CI: 0.05, 0.10), and the diagnostic odds ratio was 249.81 (95% CI: 125.12, 498.74). The area under the receiver operator characteristic curve was 0.98 (95% CI: 0.96, 0.99).

Conclusion

MR imaging with Gd-EOB-DTPA is a reliable, non-invasive, and no-radiation-exposure imaging modality with a high sensitivity and specificity for detection of liver metastases. Nonetheless, it should be applied cautiously, and large scale, well-designed trials are necessary to assess its clinical value.     

Diagnostic test accuracy for detecting Schistosoma japonicum and S. mekongi in humans: A systematic review and meta-analysis

BackgroundMost of national schistosomiasis elimination programmes in Asia are relying on stool examination, particularly Kato Katz stool examination technique for regular transmission monitoring. However, the Kato-Katz technique has shown low sensitivity for the detection of light-intensity infections, and therefore highly sensitive diagnostic tools are urgently required to monitor prevalence of infection in low transmission settings. The objective of this systematic review was to evaluate and synthesize the performance of diagnostic tests for detecting Schistosoma japonicum and S. mekongi infection in people living in endemic areas.Methodology/Principal findingsWe comprehensively searched these nine electronic databases and other resources until July 2019, with no language or publication limits: PubMed, EMBASE, MEDLINE, Web of Science, BIOSIS Citation Index, HTA, CINAHL PLUS, The Cochrane Library, and PsycINFO. We included original studies that assessed diagnostic performance using antibody, antigen, and molecular tests with stool examination test as a reference standard. Two reviewers independently extracted a standard set of data and assessed study quality. We estimated the pooled estimates of sensitivity and specificity for each index test. We used diagnostic odds ratio to determine the overall accuracy and hierarchical summary receiver operating characteristics (HSROC) curve to assess the index tests performance.Fifteen studies (S. japonicum [n = 13] and S. mekongi [n = 2]) testing 15,303 participants were included in the review. Five studies reported performance of enzyme-linked immunosorbent assay (ELISA), seven studies reported indirect hemagglutination assay (IHA), and four studies reported polymerase chain reaction (PCR) for detecting S. japonicum. The pooled sensitivity and specificity were 0.93 (95% CI: 0.84–0.98) and 0.40 (95% CI: 0.29–0.53) for ELISA, 0.97 (95% CI: 0.90–0.99) and 0.66 (95% CI: 0.58–0.73) for IHA, and 0.89 (95% CI: 0.71–0.96) and 0.49 (95% CI: 0.29–0.69) for PCR respectively. A global summary indicated the best performance for IHA, closely followed by ELISA. We were unable to perform meta-analysis for S. mekongi due to insufficient number of studies.Conclusions/SignificanceIHA showed the highest detection accuracy for S. japonicum. Further studies are needed to determine the suitable diagnostic methods to verify the absence of transmission of S. mekongi and also to compare detection accuracy against more sensitive reference standards such as PCR.     

Diagnostic and prognostic value of miR-200 family in breast cancer: A meta-analysis and systematic review

BackgroundBreast cancer (BC) is the most common cancer for women all over the world. Great interests have been paid to discover accurate and noninvasive methods for breast cancer diagnosis and prognosis. Although the diagnostic and prognostic value of microRNA-200 (miRNA- 200, miR-200) family has been revealed in many studies, the results were inconsistent. Thus, this meta-analysis aims to assess the overall value of miRNA-200 family in breast cancer diagnosis and prognosis.MethodRelevant studies were searched from the following databases: PubMed, PMC, EMBASE, and ScienceDirect using key words: ("miRNA-200 family" or "miR-141" or "miR-200a" or "miR-200b" or "miR-200c" or "miR-429") and (“HER2” or “Luminal A” or “Luminal B” or “TNBC”) and ("breast cancers" or "breast carcinoma" or "breast malignancy" or "breast tumor"). The sensitivity, specificity, AUC were then calculated to estimate the diagnostic accuracy of the miR-200 family. As for the prognostic value of the miR-200 family, the pooled hazard ratio (HR) was assessed. Heterogeneity among individual studies was also examined by subgroup analyses.ResultA total of 24 articles were included in the meta-analysis. The diagnostic value of miR-200s in BC was presented by the pooled sensitivity was 0.86 (95% CI: 0.83-0.88); the pooled specificity was 0.82 (95% CI: 0.72-0.89); the pooled AUC was 0.931 (95% CI: 0.919-0.942). Besides, expression of miR-200s in metastatic breast cancer has sensitivity, specificity and AUC of 0.70 (95%CI: 0.56-0.81), 0.72 (95%CI: 0.61-0.81), and 0.814 (95%CI: 0.741-0.903), respectively. The meta-analysis then revealed that high expression of miR-200 family corresponded to poor OS (HR: 1.63, 95% CI: 1.03-2.52), poor DFS (HR: 1.55, 95% CI: 0.95-2.56) in BC patients while downregulation of miRNA-200s corresponded to poor OS (HR= 0.84, 95%CI: 0.46-1.63) in TNBC patients and poor OS (HR=0.49; 95%CI: 0.27-0.88) in luminal BC patient.ConclusionThe MiR-200 family has high diagnostic accuracy and can be used as an important biomarker to prognosticate breast cancer.     

16S Ribosomal Ribonucleic Acid Gene Polymerase Chain Reaction in the Diagnosis of Bloodstream Infections: A Systematic Review and Meta-Analysis

ObjectiveWe aim to evaluate the accuracy of the 16S ribosomal ribonucleic acid (rRNA) gene polymerase chain reaction (PCR) test in the diagnosis of bloodstream infections through a systematic review and meta-analysis.MethodsA computerized literature search was conducted to identify studies that assessed the diagnostic value of 16S rRNA gene PCR test for bloodstream infections. Study quality was assessed using the revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We calculated the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and their 95% confidence intervals (95% CI) for each study. Summary receiver operating characteristic (SROC) curve was used to summarize overall test performance. Statistical analysis was performed in Meta-DiSc 1.4 and Stata/SE 12.0 software.ResultsTwenty-eight studies were included in our meta-analysis. Using random-effect model analysis, the pooled sensitivity, specificity, PLR, NLR, and DOR were 0.87 (95% CI, 0.85–0.89), 0.94 (95% CI, 0.93–0.95), 12.65 (95% CI, 8.04–19.90), 0.14 (95% CI, 0.08–0.24), and 116.76 (95% CI, 52.02–262.05), respectively. The SROC curve indicated that the area under the curve (AUC) was 0.9690 and the maximum joint sensitivity and specificity (Q*) was 0.9183. In addition, heterogeneity was statistically significant but was not caused by the threshold effect.ConclusionExisting data suggest that 16S rRNA gene PCR test is a practical tool for the rapid screening of sepsis. Further prospective studies are needed to assess the diagnostic value of PCR amplification and DNA microarray hybridization of 16S rRNA gene in the future.     

The Prevalence of Anatomical Variations of the Median Nerve in the Carpal Tunnel: A Systematic Review and Meta-Analysis

ResultsThirty-one studies (n = 3918 hands) were included in the meta-analysis. The pooled prevalence rates of the extraligamentous, subligamentous, and transligamentous courses were 75.2% (95%CI:55.4%-84.7%), 13.5% (95%CI:3.6%-25.7%), and 11.3% (95%CI:2.4%-23.0%), respectively. The prevalence of Lanz group 2, 3, and 4 were 4.6% (95%CI:1.6%-9.1%), 2.6% (95%CI:0.1%-2.8%), and 2.3% (95%CI:0.3%-5.6%), respectively. Ulnar side of branching of the TMB was found in 2.1% (95%CI:0.9%-3.6%) of hands. The prevalence of hypertrophic thenar muscles over the transverse carpal ligament was 18.2% (95%CI:6.8%-33.0%). A transligamentous course of the TMB was more commonly found in hands with hypertrophic thenar muscles (23.4%, 95%CI:5.0%-43.4%) compared to those without hypertrophic musculature (1.7%, 95%CI:0%-100%). In four studies (n = 423 hands), identical bilateral course of the TMB was found in 72.3% (95%CI:58.4%-84.4%) of patients.ConclusionsAnatomical variations in the course of the TMB and the MN in the carpal tunnel are common in the population. Thus, we recommend an ulnar side approach to carpal tunnel release, with a careful layer by layer dissection, to avoid iatrogenic damage to the TMB.     

Serum MicroRNA-21 as a Diagnostic Marker for Lung Carcinoma: A Systematic Review and Meta-Analysis

Objectives

MicroRNA-21 in serum is a promising marker for the diagnosis of lung carcinoma. A meta-analysis was performed to assess the diagnostic accuracy and clinical value of serum microRNA-21 in patients with lung carcinoma.

Methods

PubMed, EMBASE, Web of Knowledge (ISI), the Cochrane Library, Scopus, BioMed Central, Science Direct, China National Knowledge Infrastructure (CNKI), Wan Fang data and Technology of Chongqing (VIP) databases were searched to identify studies in English and Chinese that assessed the diagnostic value of serum miR-21 for lung carcinoma, from inception to 9 April 2014. Two independent investigators identified and extracted the study characteristics from all articles according to defined inclusion and exclusion criteria. Quality assessment of diagnostic accuracy studies (QUADAS) was used to score the quality of the eligible studies. Stata12 and Meta-DiSc software were used to test the heterogeneity and to perform the meta-analysis.

Results

Our search returned 1008 articles, of which seven fulfilled the inclusion criteria, accounting for 500 patients and 386 controls. Using random-effect model analysis, the summary assessments revealed that the mean sensitivity was 0.71% (95%CI: 57–82%) and specificity was 0.84% (95%CI: 76–89%). The area under the receiver operating characteristic curve was 0.86 (95%CI: 0.83–0.89). In addition, heterogeneity was clearly apparent but was not caused by the threshold effect, as shown by Meta-DiSc analysis.

Conclusion

The current evidence suggests that serum miR-21 can be rapidly measured in lung carcinoma patients and has potential diagnostic value with moderate sensitivity and specificity. Further prospective studies to assess the early stage diagnostic value are needed in the future.     

Diagnostic Accuracy of Ber-EP4 for Metastatic Adenocarcinoma in Serous Effusions: A Meta-Analysis

Numerous studies have investigated the utility of Ber-EP4 in differentiating metastatic adenocarcinoma (MAC) from malignant epithelial mesothelioma (MM) and/or reactive mesothelial cells (RM) in serous effusions. However, the results remain controversial. The aim of this study is to determine the overall accuracy of Ber-EP4 in serous effusions for MAC through a meta-analysis of published studies. Publications addressing the accuracy of Ber-EP4 in the diagnosis of MAC were selected from the Pubmed, Embase and Cochrane Library. Data from selected studies were pooled to yield summary sensitivity, specificity, positive and negative likelihood ratio (LR), diagnostic odds ratio (DOR), and receiver operating characteristic (SROC) curve. Statistical analysis was performed by Meta-Disc 1.4 and STATA 12.0 softwares. 29 studies, based on 2646 patients, met the inclusion criteria and the summary estimating for Ber-EP4 in the diagnosis of MAC were: sensitivity 0.8 (95% CI: 0.78–0.82), specificity 0.94 (95% CI: 0.93–0.96), positive likelihood ratio (PLR) 12.72 (95% CI: 8.66–18.7), negative likelihood ratio (NLR) 0.18 (95% CI: 0.12–0.26) and diagnostic odds ratio 95.05 (95% CI: 57.26–157.77). The SROC curve indicated that the maximum joint sensitivity and specificity (Q-value) was 0.91; the area under the curve was 0.96. Our findings suggest that BER-EP4 may be a useful diagnostic adjunctive tool for confirming MAC in serous effusions.     

Evaluation of the Diagnostic Performance of Magnetic Resonance Spectroscopy in Brain Tumors: A Systematic Review and Meta-Analysis

Object

The aim of this study was to determine the suitability of magnetic resonance spectroscopy (MRS) for screening brain tumors, based on a systematic review and meta-analysis of published data on the diagnostic performance of MRS.

Methods

The PubMed and PHMC databases were systematically searched for relevant studies up to December 2013. The sensitivities and specificities of MRS in individual studies were calculated and the pooled diagnostic accuracies, with 95% confidence intervals (CI), were assessed under a fixed-effects model.

Results

Twenty-four studies were included, comprising a total of 1013 participants. Overall, no heterogeneity of diagnostic effects was observed between studies. The pooled sensitivity and specificity of MRS were 80.05% (95% CI = 75.97%–83.59%) and 78.46% (95% CI: 73.40%–82.78%), respectively. The area under the summary receiver operating characteristic curve was 0.78. Stratified meta analysis showed higher sensitivity and specificity in child than adult. CSI had higher sensitivity and SV had higher specificity. Higher sensitivity and specificity were obtained in short TE value.

Conclusion

Although the qualities of the studies included in the meta-analysis were moderate, current evidence suggests that MRS may be a valuable adjunct to magnetic resonance imaging for diagnosing brain tumors, but requires selection of suitable technique and TE value.     

Contrast-Enhanced Ultrasonography in Differential Diagnosis of Benign and Malignant Ovarian Tumors

Objective

To evaluate the accuracy of contrast-enhanced ultrasonography (CEUS) in differential diagnosis of benign and malignant ovarian tumors.

Methods

The scientific literature databases PubMed, Cochrane Library and CNKI were comprehensively searched for studies relevant to the use of CEUS technique for differential diagnosis of benign and malignant ovarian cancer. Pooled summary statistics for specificity (Spe), sensitivity (Sen), positive and negative likelihood ratios (LR⁺/LR⁻), and diagnostic odds ratio (DOR) and their 95%CIs were calculated. Software for statistical analysis included STATA version 12.0 (Stata Corp, College Station, TX, USA) and Meta-Disc version 1.4 (Universidad Complutense, Madrid, Spain).

Results

Following a stringent selection process, seven high quality clinical trials were found suitable for inclusion in the present meta-analysis. The 7 studies contained a combined total of 375 ovarian cancer patients (198 malignant and 177 benign). Statistical analysis revealed that CEUS was associated with the following performance measures in differential diagnosis of ovarian tumors: pooled Sen was 0.96 (95%CI = 0.92∼0.98); the summary Spe was 0.91 (95%CI = 0.86∼0.94); the pooled LR⁺ was 10.63 (95%CI = 6.59∼17.17); the pooled LR− was 0.04 (95%CI = 0.02∼0.09); and the pooled DOR was 241.04 (95% CI = 92.61∼627.37). The area under the SROC curve was 0.98 (95% CI = 0.20∼1.00). Lastly, publication bias was not detected (t = −0.52, P = 0.626) in the meta-analysis.

Conclusions

Our results revealed the high clinical value of CEUS in differential diagnosis of benign and malignant ovarian tumors. Further, CEUS may also prove to be useful in differential diagnosis at early stages of this disease.     

Late-Night Salivary Cortisol for the Diagnosis of Cushing Syndrome: a Meta-Analysis

ObjectiveTo report a meta-analysis of late-night salivary cortisol testing for the diagnosis of Cushing syndrome.MethodsMEDLINE and EMBASE computer databases were searched to identify relevant articles published between January 1950 and December 2007. The search strategy used the following medical subject headings and keywords: cortisol, Cushing or Cushing’s, saliva, salivary, late-night, nocturnal, and nighttime. The results were limited to studies in humans older than 18 years. Titles and abstracts of all articles, as well as full text of relevant articles, were reviewed. Sensitivity, specificity, likelihood ratio positive, likelihood ratio negative, and diagnostic odds ratio were extracted by 2 authors. Discrepancies were resolved by mediation and discussion with a third author.ResultsSeven articles contained sufficient information to be included in the analysis. A total of 947 patients (339 with Cushing syndrome) were identified. Pooled data from the 7 studies revealed a sensitivity of 92% (95% confidence interval [CI], 88%-94%), specificity of 96% (95% CI, 94%-97%), and diagnostic odds ratio of 311 (95% CI, 92-1059). Likelihood ratio positive was 21 (95% CI, 1043), with a likelihood ratio negative of 0.08 (95% CI, 0.02-0.32). Inconsistencies for each of these results measured by the I² statistic ranged from moderate to high.ConclusionThis analysis demonstrates that latenight salivary cortisol has excellent diagnostic characteristics and as such, is a robust, convenient test for screening and diagnosis of Cushing syndrome. (Endocr Pract. 2009;15:335-342)     

Assessment of the Potential Diagnostic Role of Anaplastic Lymphoma Kinase for Inflammatory Myofibroblastic Tumours: A Meta-Analysis

Objective

To assess the value of anaplastic lymphoma kinase for the diagnosis of inflammatory myofibroblastic tumours using a comprehensive meta-analysis.

Methods

We searched the related literature using electronic databases and manual searches. Approximately 454 cases from several countries were included in this analysis. The quality of studies included was assessed by QUADAS (quality assessment of studies of diagnostic accuracy). The diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), sensitivity and specificity were calculated to assess the role of anaplastic lymphoma kinase in the diagnosis of inflammatory myofibroblastic tumours. The overall test performance was summarised by an SROC (summary receiver operating characteristic curve). The heterogeneity and publication bias were analysed using Meta-regression and Deeks'' test. All data were analysed by Stata 12.0 software.

Results

Eight studies were included according to our inclusion criteria. The overall results for the specificity, sensitivity, PLR, NLR, DOR and area under the curve (AUC) were 0.99 (95% CI 0.82-1.00), 0.67 (95% CI 0.46-0.83), 0.67 (95% CI 0.46-0.83), 60.6 (95% CI 3.3-1112.4), 0.33 (95% CI 0.19-0.60), 181 (95% CI 9-3684) and 0.95 (95% CI 0.93-0.97), respectively, while the specificity, sensitivity, PLR, NLR, DOR and AUC for bladder IMTs were 0.99 (95% CI 0.67-1.00), 0.86 (95% CI 0.58-0.96), 95.6 (95% CI 2.0-4616.2), 0.14 (95% CI 0.04-0.50), 671 (95% CI 16-28913) and 0.99 (95% CI 0.97-0.99), respectively.

Conclusion

The present meta-analysis indicated that anaplastic lymphoma kinase plays a significant role in the differential diagnosis of inflammatory myofibroblastic tumours, particularly for inflammatory myofibroblastic tumours of the urinary bladder.     

Diagnostic accuracy of antigen detection in urine and molecular assays testing in different clinical samples for the diagnosis of progressive disseminated histoplasmosis in patients living with HIV/AIDS: A prospective multicenter study in Mexico

BackgroundThe progressive disseminated histoplasmosis (PDH) has been associated with severe disease and high risk of death among people living with HIV (PLWHIV). Therefore, the purpose of this multicenter, prospective, double-blinded study done in ten Mexican hospitals was to determine the diagnostic accuracy of detecting Histoplasma capsulatum antigen in urine using the IMMY ALPHA Histoplasma EIA kit (IAHE), clarus Histoplasma GM Enzyme Immunoassay (cHGEI IMMY) and MiraVista Histoplasma Urine Antigen LFA (MVHUALFA); as well as the Hcp100 and 1281-1283₂₂₀SCAR nested PCRs in blood, bone-marrow, tissue biopsies and urine.Methodology/Principal findingsWe included 415 PLWHIV older than 18 years of age with suspicion of PDH. Using as diagnostic standard recovery of H. capsulatum in blood, bone marrow or tissue cultures, or histopathological exam compatible, detected 108 patients (26%, [95%CI, 21.78–30.22]) with proven-PDH. We analyzed 391 urine samples by the IAHE, cHGEI IMMY and MVHUALFA; the sensitivity/specificity values obtained were 67.3% (95% CI, 57.4–76.2) / 96.2% (95% CI, 93.2–98.0) for IAHE, 91.3% (95% CI, 84.2–96.0) / 90.9% (95% CI, 87.0–94.0) for cHGEI IMMY and 90.4% (95% CI, 83.0–95.3) / 92.3% (95% CI, 88.6–95.1) for MVHUALFA.The Hcp100 nested PCR was performed on 393, 343, 75 and 297, blood, bone marrow, tissue and urine samples respectively; the sensitivity/specificity values obtained were 62.9% (95%CI, 53.3–72.5)/ 89.5% (95%CI, 86.0–93.0), 65.9% (95%CI, 56.0–75.8)/ 89.0% (95%CI, 85.2–92.9), 62.1% (95%CI, 44.4–79.7)/ 82.6% (95%CI, 71.7–93.6) and 34.9% (95%CI, 24.8–46.2)/ 67.3% (95%CI, 60.6–73.5) respectively; and 1281-1283₂₂₀SCAR nested PCR was performed on 392, 344, 75 and 291, respectively; the sensitivity/specificity values obtained were 65.3% (95% CI, 55.9–74.7)/ 58.8% (95%CI, 53.2–64.5), 70.8% (95%CI, 61.3–80.2)/ 52.9% (95%CI, 46.8–59.1), 71.4% (95%CI, 54.7–88.2)/ 40.4% (95%CI, 26.4–54.5) and 18.1% (95%CI, 10.5–28.1)/ 90.4% (95%CI, 85.5–94.0), respectively.Conclusions/SignificanceThe cHGEI IMMY and MVHUALFA tests showed excellent performance for the diagnosis of PDH in PLWHIV. The integration of these tests in clinical laboratories will certainly impact on early diagnosis and treatment.     

Assessment of the Incremental Benefit of Computer-Aided Detection (CAD) for Interpretation of CT Colonography by Experienced and Inexperienced Readers

Objectives

To quantify the incremental benefit of computer-assisted-detection (CAD) for polyps, for inexperienced readers versus experienced readers of CT colonography.

Methods

10 inexperienced and 16 experienced radiologists interpreted 102 colonography studies unassisted and with CAD utilised in a concurrent paradigm. They indicated any polyps detected on a study sheet. Readers’ interpretations were compared against a ground-truth reference standard: 46 studies were normal and 56 had at least one polyp (132 polyps in total). The primary study outcome was the difference in CAD net benefit (a combination of change in sensitivity and change in specificity with CAD, weighted towards sensitivity) for detection of patients with polyps.

Results

Inexperienced readers’ per-patient sensitivity rose from 39.1% to 53.2% with CAD and specificity fell from 94.1% to 88.0%, both statistically significant. Experienced readers’ sensitivity rose from 57.5% to 62.1% and specificity fell from 91.0% to 88.3%, both non-significant. Net benefit with CAD assistance was significant for inexperienced readers but not for experienced readers: 11.2% (95%CI 3.1% to 18.9%) versus 3.2% (95%CI -1.9% to 8.3%) respectively.

Conclusions

Concurrent CAD resulted in a significant net benefit when used by inexperienced readers to identify patients with polyps by CT colonography. The net benefit was nearly four times the magnitude of that observed for experienced readers. Experienced readers did not benefit significantly from concurrent CAD.     

Diagnostic Value of Mutation-Specific Antibodies for Immunohistochemical Detection of Epidermal Growth Factor Receptor Mutations in Non-Small Cell Lung Cancer: A Meta-Analysis

Background

Various studies have assessed the diagnostic accuracy of EGFR mutation-specific antibodies in non-small cell lung cancer (NSCLC). We performed a meta-analysis of existing data to investigate the diagnostic value of mutation-specific antibodies for detection of EGFR mutations in NSCLC.

Methods

We systematically retrieved relevant studies from PubMed, Web of Knowledge, and Google Scholar. Data from studies that met the inclusion criteria were extracted for further exploration of heterogeneity, including calculation of the average sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and analysis of SROC(summary receiver operating characteristic) curves.

Results

Fifteen studies met our inclusion criteria. A summary of the meta-analysis of the efficacy of the anti-E746-A750 antibody was as follows: sensitivity, 0.60 (95% CI, 0.55–0.64); specificity, 0.98 (95% CI, 0.97–0.98); PLR, 33.50 (95% CI, 13.96–80.39); NLR, 0.39 (95% CI, 0.30–0.51) and DOR, 111.17 (95% CI, 62.22–198.63). A similar meta-analysis was performed for the anti-L858R antibody with results as follows: sensitivity, 0.76 (95% CI, 0.71–0.79); specificity, 0.96 (95% CI, 0.95–0.97); PLR, 24.42 (95% CI, 11.66–51.17); NLR, 0.22 (95% CI, 0.12–0.39) and DOR, 126.66 (95% CI, 54.60–293.82).

Conclusion

Immunohistochemistry alone is sufficient for the detection of EGFR mutations if the result is positive. Molecular-based analyses are necessary only if the anti-E746-A750 antibody results are negative. Immunohistochemistry seems more suitable for clinical screening for EGFR mutations prior to molecular-based analysis.