Significance of Serum Pepsinogens as a Biomarker for Gastric Cancer and Atrophic Gastritis Screening: A Systematic Review and Meta-Analysis

Background

Human pepsinogens are considered promising serological biomarkers for the screening of atrophic gastritis (AG) and gastric cancer (GC). However, there has been controversy in the literature with respect to the validity of serum pepsinogen (SPG) for the detection of GC and AG. Consequently, we conducted a systematic review and meta-analysis to assess the diagnostic accuracy of SPG in GC and AG detection.

Methods

We searched PubMed, Embase, and the Chinese National Knowledge Infrastructure (CNKI) for correlative original studies published up to September 30, 2014. The summary sensitivity, specificity, positive diagnostic likelihood ratio (DLR+), negative diagnostic likelihood ratio (DLR-), area under the summary receiver operating characteristic curve (AUC) and diagnostic odds ratio (DOR) were used to evaluate SPG in GC and AG screening based on bivariate random effects models. The inter-study heterogeneity was evaluated by the I² statistics and publication bias was assessed using Begg and Mazumdar’s test. Meta-regression and subgroup analyses were performed to explore study heterogeneity.

Results

In total, 31 studies involving 1,520 GC patients and 2,265 AG patients were included in the meta-analysis. The summary sensitivity, specificity, DLR+, DLR-, AUC and DOR for GC screening using SPG were 0.69 (95% CI: 0.60–0.76), 0.73 (95% CI: 0.62–0.82), 2.57 (95% CI: 1.82–3.62), and 0.43 (95% CI: 0.34–0.54), 0.76 (95% CI: 0.72–0.80) and 6.01 (95% CI: 3.69–9.79), respectively. For AG screening, the summary sensitivity, specificity, DLR+, DLR-, AUC and DOR were 0.69 (95% CI: 0.55–0.80), 0.88 (95% CI: 0.77–0.94), 5.80 (95% CI: 3.06–10.99), and 0.35 (95% CI: 0.24–0.51), 0.85 (95% CI: 0.82–0.88) and 16.50 (95% CI: 8.18–33.28), respectively. In subgroup analysis, the use of combination of concentration of PGI and the ratio of PGI:PGII as measurement of SPG for GC screening yielded sensitivity of 0.70 (95% CI: 0.66–0.75), specificity of 0.79 (95% CI: 0.79–0.80), DOR of 6.92 (95% CI: 4.36–11.00), and AUC of 0.78 (95% CI: 0.72–0.81), while the use of concentration of PGI yielded sensitivity of 0.55 (95% CI: 0.51–0.60), specificity of 0.79 (95% CI: 0.76–0.82), DOR of 6.88 (95% CI: 2.30–20.60), and AUC of 0.77 (95% CI: 0.73–0.92). For AG screening, the use of ratio of PGI:PGII as measurement of SPG yielded sensitivity of 0.69 (95% CI: 0.52–0.83), specificity of 0.84 (95% CI: 0.68–0.93), DOR of 11.51 (95% CI: 6.14–21.56), and AUC of 0.83 (95% CI: 0.80–0.86), the use of combination of concentration of PGI and the ratio of PGI:PGII yield sensitivity of 0.79 (95% CI: 0.72–0.85), specificity of 0.89 (95% CI: 0.85–0.93), DOR of 24.64 (95% CI: 6.95–87.37), and AUC of 0.87 (95% CI: 0.81–0.92), concurrently, the use of concentration of PGI yield sensitivity of 0.46 (95% CI: 0.38–0.54), specificity of 0.93 (95% CI: 0.91–0.95), DOR of 19.86 (95% CI: 0.86–456.91), and AUC of 0.86 (95% CI: 0.52–1.00).

Conclusion

SPG has great potential as a noninvasive, population-based screening tool in GC and AG screening. In addition, given the potential publication bias and high heterogeneity of the included studies, further high quality studies are required in the future.     

Diagnostic Accuracy of Natriuretic Peptides for Heart Failure in Patients with Pleural Effusion: A Systematic Review and Updated Meta-Analysis

Background

Previous studies have reported that natriuretic peptides in the blood and pleural fluid (PF) are effective diagnostic markers for heart failure (HF). These natriuretic peptides include N-terminal pro-brain natriuretic peptide (NT-proBNP), brain natriuretic peptide (BNP), and midregion pro-atrial natriuretic peptide (MR-proANP). This systematic review and meta-analysis evaluates the diagnostic accuracy of blood and PF natriuretic peptides for HF in patients with pleural effusion.

Methods

PubMed and EMBASE databases were searched to identify articles published in English that investigated the diagnostic accuracy of BNP, NT-proBNP, and MR-proANP for HF. The last search was performed on 9 October 2014. The quality of the eligible studies was assessed using the revised Quality Assessment of Diagnostic Accuracy Studies tool. The diagnostic performance characteristics (sensitivity, specificity, and other measures of accuracy) were pooled and examined using a bivariate model.

Results

In total, 14 studies were included in the meta-analysis, including 12 studies reporting the diagnostic accuracy of PF NT-proBNP and 4 studies evaluating blood NT-proBNP. The summary estimates of PF NT-proBNP for HF had a diagnostic sensitivity of 0.94 (95% confidence interval [CI]: 0.90–0.96), specificity of 0.91 (95% CI: 0.86–0.95), positive likelihood ratio of 10.9 (95% CI: 6.4–18.6), negative likelihood ratio of 0.07 (95% CI: 0.04–0.12), and diagnostic odds ratio of 157 (95% CI: 57–430). The overall sensitivity of blood NT-proBNP for diagnosis of HF was 0.92 (95% CI: 0.86–0.95), with a specificity of 0.88 (95% CI: 0.77–0.94), positive likelihood ratio of 7.8 (95% CI: 3.7–16.3), negative likelihood ratio of 0.10 (95% CI: 0.06–0.16), and diagnostic odds ratio of 81 (95% CI: 27–241). The diagnostic accuracy of PF MR-proANP and blood and PF BNP was not analyzed due to the small number of related studies.

Conclusions

BNP, NT-proBNP, and MR-proANP, either in blood or PF, are effective tools for diagnosis of HF. Additional studies are needed to rigorously evaluate the diagnostic accuracy of PF and blood MR-proANP and BNP for the diagnosis of HF.     

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.     

Diagnostic Evaluation of Des-Gamma-Carboxy Prothrombin versus α-Fetoprotein for Hepatitis B Virus-Related Hepatocellular Carcinoma in China: A Large-Scale,Multicentre Study

An efficient serum marker for hepatocellular carcinoma (HCC) is currently lacking and requires intensive exploration. We aimed to evaluate the performance of des-gamma-carboxy prothrombin (DCP) for identifying hepatitis B virus-related HCC in a large, multicentre study in China. A total of 1034 subjects in three cohorts (A, B, and C) including HCC and various non-HCC controls were enrolled from 4 academic medical centers in China from January 2011 to February 2014. Blind parallel detections were conducted for DCP and AFP. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic efficacies. In cohort A, which comprised 521 subjects, including patients with HCC, liver metastasis, liver cirrhosis (LC), and liver hemangiomas as well as healthy controls (HCs), the accuracy of DCP for distinguishing HCC from various controls was 6.2–9.7% higher than that of AFP. In cohort B, which comprised 447 subjects, including patients with HCC, LC, and chronic hepatitis B as well as HC, the accuracy of DCP was further elevated (12.3–20.67% higher than that of AFP). The superiority of DCP to AFP was more profound in the surveillance of early HCC [AUC 0.837 (95% CI: 0.771–0.903) vs. 0.650 (0.555–0.745)] and AFP-negative HCC [AUC: 0.856 (0.798–0.914)] and in discriminating HCC from LC (accuracy: 92.9% vs.64.71%). Higher DCP levels were associated with worse clinical behaviors and shorter disease-free survival. DCP not only is complementary to AFP in identifying AFP-negative HCC and in excluding AFP-positive non-HCC (liver cirrhosis), but also demonstrates improved performance in HCC surveillance, early diagnosis, treatment response and recurrence monitoring in the HBV-related population.     

Evaluation of GeneXpert vanA/vanB in the early diagnosis of vancomycin-resistant enterococci infection

PurposeVancomycin-resistant enterococci infection is a worrying worldwide clinical problem. To evaluate the accuracy of GeneXpert vanA/vanB in the diagnosis of VRE, we conducted a systematic review in the study.MethodsExperimental data were extracted from publications until May 03 2021 related to the diagnostic accuracy of GeneXpert vanA/vanB for VRE in PubMed, Embase, Web of Science and the Cochrane Library. The accuracy of GeneXpert vanA/vanB for VRE was evaluated using summary receiver to operate characteristic curve, pooled sensitivity, pooled specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio.Results8 publications were divided into 3 groups according to two golden standard references, vanA and vanB group, vanA group, vanB group, including 6 researches, 5 researches and 5 researches, respectively. The pooled sensitivity and specificity of group vanA and vanB were 0.96 (95% CI, 0.93–0.98) and 0.90 (95% CI, 0.88–0.91) respectively. The DOR was 440.77 (95% CI, 37.92–5123.55). The pooled sensitivity and specificity of group vanA were 0.86 (95% CI, 0.81–0.90) and 0.99 (95% CI, 0.99–0.99) respectively, and those of group vanB were 0.85 (95% CI, 0.63–0.97) and 0.82 (95% CI, 0.80–0.83) respectively.ConclusionGeneXpert vanA/vanB can diagnose VRE with high-accuracy and shows greater accuracy in diagnosing vanA.     

Evaluation of White Cell Count and Differential in Synovial Fluid for Diagnosing Infections after Total Hip or Knee Arthroplasty

Background

The accuracy of synovial fluid (SF) white cell count (WCC) and polymorphonuclear (PMN) cell evaluation for predicting prosthetic joint infection (PJI) at the total hip arthroplasty (THA) or total knee arthroplasty (TKA) site is unknown. Therefore, we performed a meta-analysis to summarize the diagnostic validity of SF-WCC and SF-PMN for diagnosing PJI.

Methods

The MEDLINE, EMBASE, and OVID databases were searched for studies that had evaluated the diagnostic validity of SF-WCC and SF-PMN between January 1990 and May 2013. Meta-analysis methods were used to pool sensitivity, specificity, diagnostic odd ratios (DORs), the area under the receiver-operating characteristic curve (AUC), positive likelihood ratios (PLR), negative likelihood ratios (NLR), and post-test probability. We also conducted heterogeneity, publication bias, subgroup, and meta-regression analyses.

Results

Fifteen articles (15 SF-WCC and 14 SF-PMN) that included a total of 2787 patients fulfilled the inclusion criteria and were considered for analysis. The pooled sensitivity and specificity for PJI detection was 0.88 (95% confidence intervals [CI], 0.81–0.93) and 0.93 (95% CI, 0.88–0.96) for SF-WCC and 0.90 (95% CI, 0.84–0.93) and 0.88 (95% CI, 0.83–0.92) for SF-PMN, respectively. The AUC was 0.96 for SF-WCC and 0.95 for SF-PMN. PLR and NLR were 13.3 and 0.13 for SF-WCC, and 7.6 and 0.12 for SF-PMN, respectively. There was no evidence of publication bias. Low-clinical-scenario (pre-test probability, 20%) post-test probabilities were 3% for both negative SF-WCC and SF-PMN results. The subgroup analyses indicated that the sensitivity/specificity of THA were 0.73/0.96 for SF-WCC and 0.85/0.83 for SF-PMN, whereas those of TKA were 0.90/0.91 for SF-WCC and 0.90/0.88 for SF-PMN. We also found that collection of SF-WCC preoperatively had a higher sensitivity than that obtained intraoperatively (0.91 vs. 0.77).

Conclusions

SF-WCC and SF-PMN have an adequate and clinically acceptable diagnostic value for detecting PJI, particularly after TKA.     

Gadoxetic Acid Disodium-Enhanced Magnetic Resonance Imaging for the Detection of Hepatocellular Carcinoma: A Meta-Analysis

Objective

To determine the accuracy of MR imaging with gadoxetic acid disodium (Gd-EOB-DTPA) for the detection of hepatocelluar carcinoma (HCC).

Materials and Methods

A systematic search was performed in PUBMED, EMBASE, Web of Science, Cochrane Library and the Chinese Biomedical Literature Database up to March 2013 to identify studies about evaluation of Gd-EOB-DTPA enhanced MR imaging in patients suspected of having HCC. The data were extracted to perform heterogeneity test and threshold effect test and to calculate sensitivity, specificity, diagnostic odds ratio, predictive value, and areas under summary receiver operating characteristic curve (AUC).

Results

From 601 citations, 10 were included in the meta-analysis. The methodological quality of the 10 studies was good. Overall HCC: There was significant heterogeneity in the pooled analysis (I² = 69.4%, P = 0.0005), and the pooled weighted values were determined to be sensitivity: 0.91 (95% confidence interval (CI): 0.89, 0. 93); specificity: 0.95 (95% CI: 0.94, 0.96); diagnostic odds ratio: 169.94 (95% CI: 108.84, 265.36); positive likelihood ratio: 15.75 (95% CI: 7.45, 33.31); negative likelihood ratio: 0.10 (95% CI: 0.06, 0.15). The AUC was 0.9778. HCC in cirrhosis: The estimates were to be sensitivity: 0.91 (95% CI: 0.88, 0.93); specificity: 0.93 (95% CI: 0.89, 0.95); diagnostic odds ratio: 234.24 (95% CI: 33.47, 1639.25); positive likelihood ratio: 15.08 (95% CI: 2.20, 103.40); negative likelihood ratio: 0.08 (95% CI: 0.03, 0.21). The AUC was 0.9814. ≤20 mm HCC: The AUC was 0.9936. There was no notable publication bias.

Conclusions

This meta-analysis suggests that MR imaging with Gd-EOB-DTPA has high diagnostic accuracy for the detection of HCC, especially for ≤20 mm HCC. This technique shows good prospect in diagnosis of HCC.     

Preoperative Evaluation of the Histological Grade of Hepatocellular Carcinoma with Diffusion-Weighted Imaging: A Meta-Analysis

ObjectiveTo evaluate the diagnostic performance of diffusion-weighted imaging (DWI) in the preoperative prediction of the histological grade of hepatocellular carcinoma (HCC).ResultsA total of 11 studies with 912 HCCs were included in this meta-analysis. The pooled sensitivity, specificity, PLR and NLR with corresponding 95% confidence intervals (CI) were 0.54(0.47–0.61), 0.90(0.87–0.93), 4.88(2.99–7.97) and 0.46(0.27–0.77) for the prediction of well-differentiated HCC (w-HCC), 0.84(0.78–0.89), 0.48(0.43–0.52), 2.29(1.43–3.69) and 0.30(0.22–0.41) for the prediction of poorly-differentiated HCC (p-HCC). The AUC were 0.9311 and 0.8513 in predicting w-HCC and p-HCC, respectively. Results were further evaluated according to the method of image interpretation. Significant heterogeneity was observed.ConclusionDWI had excellent and moderately high diagnostic accuracy for the detection of w-HCC and p-HCC, respectively. Nonetheless, further studies in larger populations and an optimized image acquisition and interpretation are required before DWI-derived parameters can be used as a useful image biomarker for the prediction of the histological grade of HCC.     

Meta-Analysis of Anti-Muscarinic Receptor Type 3 Antibodies for the Diagnosis of Sj?gren Syndrome

Purpose

To conduct a meta-analysis to evaluate the diagnostic value of anti-muscarinic receptor type 3 (M3R) antibodies in Sjögren syndrome (SS).

Methods

Two databases, PUBMED and the Cochrane Library, were systematically searched. Approximately 2,000 participants from several studies were included in this research. STATA 11.2 software and Meta-DiSc 1.4 was used to conduct the meta-analysis.

Results

Eleven studies were included in the meta-analysis. The pooled DOR was 13.00 (95% CI, 6.00–26.00). The sensitivity was 0.43 (95% CI, 0.28–0.58) and the specificity was 0.95 (95%CI, 0.91–0.97). The LR+ and LR- were 7.90 (95% CI, 4.70–13.40), 0.61 (95% CI, 0.46–0.79), respectively. The AUC was 0.89 (95% CI, 0.86–0.92).

Conclusion

The anti-M3R antibody had high specificity but relatively low sensitivity for the diagnosis of SS.     

MicroRNA-21 as a diagnostic and prognostic biomarker of lung cancer: a systematic review and meta-analysis

Background: The relationship between microRNA-21 (miRNA-21) and pathogenesis of lung cancer is a considerable focus of research interest. However, to our knowledge, no in-depth meta-analyses based on existing evidence to ascertain the value of miRNA-21 in diagnosis and clinical prognosis of lung cancer have been documented.Methods: We comprehensively searched all the literature pertaining to ‘miRNA-21’ and ‘lung cancer’ from four databases from the period of inception of each database until May 2020. Using specific inclusion and exclusion criteria, the literature for inclusion was identified and the necessary data extracted.Results: In total, 46 articles were included in the meta-analysis, among which 31 focused on diagnostic value and 15 on prognostic value. Combined sensitivity (SEN) of miRNA-21 in diagnosis of lung cancer was 0.77 (95% confidence interval (CI): 0.72–0.81), specificity (SPE) was 0.86 (95% CI: 0.80–0.90), diagnostic odds ratio (DOR) was (95% CI: 12–33), and area under the SROC curve (AUC) was 0.87 (95% CI: 0.84–0.90). No significant correlations were observed between abnormal expression of miRNA-21 and gender, smoking habits, pathological type and clinical stage of lung cancer (P>0.05). In terms of overall survival (OS), univariate analysis (hazards ratio (HR) = 1.49, 95% CI: 1.22–1.82) revealed high expression of miRNA-21 as an influencing factor for lung cancer. MiRNA-21 was confirmed as an independent risk factor for poor prognosis in multivariate analysis (HR = 1.65, 95% CI: 1.24–2.19).Conclusion: MiRNA-21 has potential clinical value in the diagnosis and prognosis of lung cancer and may serve as an effective diagnostic marker and therapeutic target in the future.     

Performance of Shear Wave Elastography for Differentiation of Benign and Malignant Solid Breast Masses

Objectives

To perform a meta-analysis assessing the ability of shear wave elastography (SWE) to identify malignant breast masses.

Methods

PubMed, the Cochrane Library, and the ISI Web of Knowledge were searched for studies evaluating the accuracy of SWE for identifying malignant breast masses. The diagnostic accuracy of SWE was evaluated according to sensitivity, specificity, and hierarchical summary receiver operating characteristic (HSROC) curves. An analysis was also performed according to the SWE mode used: supersonic shear imaging (SSI) and the acoustic radiation force impulse (ARFI) technique. The clinical utility of SWE for identifying malignant breast masses was evaluated using analysis of Fagan plot.

Results

A total of 9 studies, including 1888 women and 2000 breast masses, were analyzed. Summary sensitivities and specificities were 0.91 (95% confidence interval [CI], 0.88–0.94) and 0.82 (95% CI, 0.75–0.87) by SSI and 0.89 (95% CI, 0.81–0.94) and 0.91 (95% CI, 0.84–0.95) by ARFI, respectively. The HSROCs for SSI and ARFI were 0.92 (95% CI, 0.90–0.94) and 0.96 (95% CI, 0.93–0.97), respectively. SSI and ARFI were both very informative, with probabilities of 83% and 91%, respectively, for correctly differentiating between benign and malignant breast masses following a “positive” measurement (over the threshold value) and probabilities of disease as low as 10% and 11%, respectively, following a “negative” measurement (below the threshold value) when the pre-test probability was 50%.

Conclusions

SWE could be used as a good identification tool for the classification of breast masses.     

Diagnostic value of nucleic acid amplification tests on bronchoalveolar lavage fluid for smear-negative pulmonary tuberculosis: a meta-analysis

The diagnosis of smear-negative pulmonary tuberculosis (SNPT) remains a clinical challenge. Many studies suggest that nucleic acid amplification tests (NAATs) on bronchoalveolar lavage fluid (BALF) plays a role in diagnosing SNPT, but with considerable varying results. The current study aimed to summarize the overall diagnostic accuracy of NAATs assay on BALF for SNPT. A systematic literature search was performed and data were retrieved. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) were calculated. A summary receiver operating characteristic curve and area under the curve (AUC) were used to evaluate the overall diagnostic performance. All the statistical analysis was performed by using STATA 12.0 and Meta-DiSc 1.4 software. A total of nine studies with 1214 subjects were included this meta-analysis. The pooled sensitivity, specificity, PLR, NLR and DOR were 0.54 [95% CI (confidence interval): 0.48–0.59], 0.97 (95% CI: 0.95–0.98), 12.13 (95% CI: 8.23–17.88), 0.36 (95% CI: 0.23–0.56) and 44.71 (95% CI: 22.30–89.63) respectively. The AUC was 0.96. Estimated positive and negative post-probability values for a SNPT prevalence of 20% were 82% and 7% respectively. No publication bias was identified. Current available evidence indicated that NAATs on BALF may play a role in diagnosing SNPT, whereas the results should be interpreted in parallel with clinical information of patients and the results of traditional tests. Further studies should be performed to confirm our findings.     

Metabolites in Blood for Prediction of Bacteremic Sepsis in the Emergency Room

A metabolomics approach for prediction of bacteremic sepsis in patients in the emergency room (ER) was investigated. In a prospective study, whole blood samples from 65 patients with bacteremic sepsis and 49 ER controls were compared. The blood samples were analyzed using gas chromatography coupled to time-of-flight mass spectrometry. Multivariate and logistic regression modeling using metabolites identified by chromatography or using conventional laboratory parameters and clinical scores of infection were employed. A predictive model of bacteremic sepsis with 107 metabolites was developed and validated. The number of metabolites was reduced stepwise until identifying a set of 6 predictive metabolites. A 6-metabolite predictive logistic regression model showed a sensitivity of 0.91(95% CI 0.69–0.99) and a specificity 0.84 (95% CI 0.58–0.94) with an AUC of 0.93 (95% CI 0.89–1.01). Myristic acid was the single most predictive metabolite, with a sensitivity of 1.00 (95% CI 0.85–1.00) and specificity of 0.95 (95% CI 0.74–0.99), and performed better than various combinations of conventional laboratory and clinical parameters. We found that a metabolomics approach for analysis of acute blood samples was useful for identification of patients with bacteremic sepsis. Metabolomics should be further evaluated as a new tool for infection diagnostics.     

Association of T174M polymorphism of angiotensinogen gene with essential hypertension: A meta-analysis

The association between T174M polymorphism of angiotensinogen gene and essential hypertension risk remains controversial. We herein performed a meta-analysis to achieve a reliable estimation of their relationship. All the studies published up to May 2013 on the association between T174M polymorphism and essential hypertension risk were identified by searching the electronic repositories PubMed, MEDLINE and EMBASE, Springer, Elsevier Science Direct, Cochrane Library and Google Scholar. Data were extracted and pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. Ultimately, nine eligible studies, including 2188 essential hypertension cases and 2459 controls, were enrolled in this meta-analysis. No significant associations were found under the overall ORs for M-allele comparison (M vs. T, pooled OR 0.92, 95% CI 0.62–1.37), MM vs. TT (pooled OR 0.86, 95% CI 0.29–2.51), TM vs. TT n (pooled OR 0.91, 95% CI 0.63–1.32), recessive model (MM vs. TT+TM, pooled OR 0.89, 95% CI 0.35–2.30), dominant model (MM+TM vs. TT, pooled OR 0.91, 95% CI 0.60–1.38) between T174M polymorphism and risk for essential hypertension. This meta-analysis suggested that the T174M polymorphism of the angiotensinogen gene might not be associated with the susceptibility of essential hypertension in Asian or European populations.     

Prognostic Role of Pre-Treatment Serum AFP-L3% in Hepatocellular Carcinoma: Systematic Review and Meta-Analysis

Background

Serum lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3%) has been widely used for HCC diagnosis and follow-up surveillance as tumor serologic marker. However, the prognostic value of high pre-treatment serum AFP-L3% in patients with hepatocellular carcinoma (HCC) remains controversial. We therefore conduct a meta-analysis to assess the relationship between high pre-treatment serum AFP-L3% and clinical outcome of HCC.

Methods

Eligible studies were identified through systematic literature searches. A meta-analysis of fifteen studies (4,465 patients) was carried out to evaluate the association between high pre-treatment serum AFP-L3% and overall survival (OS) and disease-free survival (DFS) in HCC patients. Sensitivity and subgroup analyses were also conducted in this meta-analysis.

Results

Our analysis results showed that high pre-treatment serum AFP-L3% implied poor OS (HR: 1.65, 95%CI: 1.45–1.89 p<0.00001) and DFS (HR: 1.80, 95% CI: 1.49–2.17 p<0.00001) of HCC. Subgroup analysis revealed that there was association between pre-treatment serum AFP-L3% and endpoint (OS and DFS) in low AFP concentration HCC patients (HR: 1.96, 95% CI: 1.24–3.10, p = 0.004; HR: 2.53, 95% CI: 1.09–5.89, p = 0.03, respectively).

Conclusion

The current evidence suggests that high pre-treatment serum AFP-L3% levels indicated a poor prognosis for patients with HCC and AFP-L3% may have significant prognostic value in HCC patients with low AFP concentration.     

Validation of a Consensus Method for Identifying Delirium from Hospital Records

Background

Delirium is increasingly considered to be an important determinant of trajectories of cognitive decline. Therefore, analyses of existing cohort studies measuring cognitive outcomes could benefit from methods to ascertain a retrospective delirium diagnosis. This study aimed to develop and validate such a method for delirium detection using routine medical records in UK and Ireland.

Methods

A point prevalence study of delirium provided the reference-standard ratings for delirium diagnosis. Blinded to study results, clinical vignettes were compiled from participants'' medical records in a standardised manner, describing any relevant delirium symptoms recorded in the whole case record for the period leading up to case-ascertainment. An expert panel rated each vignette as unlikely, possible, or probable delirium and disagreements were resolved by consensus.

Results

From 95 case records, 424 vignettes were abstracted by 5 trained clinicians. There were 29 delirium cases according to the reference standard. Median age of subjects was 76.6 years (interquartile range 54.6 to 82.5). Against the original study DSM-IV diagnosis, the chart abstraction method gave a positive likelihood ratio (LR) of 7.8 (95% CI 5.7–12.0) and the negative LR of 0.45 (95% CI 0.40–0.47) for probable delirium (sensitivity 0.58 (95% CI 0.53–0.62); specificity 0.93 (95% CI 0.90–0.95); AUC 0.86 (95% CI 0.82–0.89)). The method diagnosed possible delirium with positive LR 3.5 (95% CI 2.9–4.3) and negative LR 0.15 (95% CI 0.11–0.21) (sensitivity 0.89 (95% CI 0.85–0.91); specificity 0.75 (95% CI 0.71–0.79); AUC 0.86 (95% CI 0.80–0.89)).

Conclusions

This chart abstraction method can retrospectively diagnose delirium in hospitalised patients with good accuracy. This has potential for retrospectively identifying delirium in cohort studies where routine medical records are available. This example of record linkage between hospitalisations and epidemiological data may lead to further insights into the inter-relationship between acute illness, as an exposure, for a range of chronic health outcomes.     

A Meta-Analysis of the Diagnostic Accuracy of Two Commercial NS1 Antigen ELISA Tests for Early Dengue Virus Detection

Background

Dengue virus (DENV) NS1 antigen detection is regarded as an early diagnostic marker. Accordingly, several studies have evaluated the performance of tests that utilize NS1 capture, but the results of individual studies may be limited due to the restricted sample size of the patients recruited. Therefore, our objective was to perform a meta-analysis of the diagnostic accuracy of two commercial NS1 ELISAs (Panbio and Platelia).

Methods and Results

Studies of interest were found in PubMed, Embase and Google Scholar databases using defined inclusion/exclusion criteria. A total of 30 studies containing 12,105 total enrolled patients were included. The results were as follows: 1) Panbio assays showed low overall performance, sensitivity 66% (95% confidence interval (CI) 61–71), specificity 99% (95% CI 96–100), positive likelihood ratio (LR+) 98 (95% CI 20–464), negative likelihood ratio (LR-) 0.3 (95% CI 0.2–0.4), diagnostic odds ratio (DOR) 289 (95% CI 59–1412); 2) Platelia assays showed high overall performance, sensitivity 74% (95% CI 63–82), specificity 99% (95% CI 97–100), LR+ 175 (95% CI 28–1099), LR- 0.3 (95% CI 0.2–0.4), DOR 663 (95% CI 98–4478). The lowest sensitivity values were for secondary infections (57% [95% CI 47–67] and 66% [95% CI 53–77] for Panbio and Platelia, respectively) and for the detection of DENV4. Regarding clinical manifestations, the sensitivity of Platelia was 69% (95% CI 43–86) and 60% (95% CI 48–70) for fever and dengue hemorrhagic fever, respectively. In addition, the sensitivity of both tests was slightly lower for samples from Southeast Asia and Oceania.

Conclusion

DENV1 samples gave higher sensitivity results for both tests. We observed that factors negatively influencing the tests, such as the type of infection, geographical origins of samples and viral serotypes, require further investigation to optimize the diagnostic accuracy.     

BNP but Not s-cTnln Is Associated with Cardioembolic Aetiology and Predicts Short and Long Term Prognosis after Cerebrovascular Events

Background

We analyzed the prognostic value of b-type natriuretic peptide (BNP) and sensitive cardiac Troponin (s-cTnI) in patients with ischemic stroke or transient ischemic attack (TIA) and their significance in predicting stroke aetiology.

Methods

In a prospectively enrolled cohort we measured BNP and s-cTnI levels upon admission. Primary endpoints were mortality, unfavorable functional outcome and stroke recurrence after 90 days and after 12 months. Secondary endpoint was cardioembolic aetiology.

Results

In 441 patients BNP but not s-cTnI remained an independent predictor for death with an adjusted HR of 1.2 (95% CI 1.1–1.4) after 90 days and 1.2 (95% CI 1.0–1.3) after one year. The comparison of the Area under Receiver Operating Characteristic (AUROC) of model A (age, NIHSS) and model B (age, NIHSS, BNP) showed an improvement in the prediction of mortality (0.85 (95% CI 0.79–0.90) vs. 0.86 (95% CI 0.81–0.92), Log Rank p = 0.004). Furthermore the category free net reclassification improvement (cfNRI) when adding BNP to the multivariate model was 57.5%, p<0.0001. For the prediction of functional outcome or stroke recurrence both markers provided no incremental value. Adding BNP to a model including age, atrial fibrillation and heart failure lead to a higher discriminatory accuracy for identification of cardioembolic stroke than the model without BNP (AUC 0.75 (95% CI 0.70–0.80) vs. AUC 0.79, (95% CI 0.75–0.84), p = 0.008).

Conclusion

BNP is an independent prognostic maker for overall mortality in patients with ischemic stroke or TIA and may improve the diagnostic accuracy to identify cardioembolic aetiology.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00390962","term_id":"NCT00390962"}}NCT00390962     

Improved Survival in Patients with Viral Hepatitis-Induced Hepatocellular Carcinoma Undergoing Recommended Abdominal Ultrasound Surveillance in Ontario: A Population-Based Retrospective Cohort Study

The optimal schedule for ultrasonographic surveillance of patients with viral hepatitis for the detection of hepatocellular carcinoma (HCC) remains unclear owing to a lack of reliable studies. We examined the timing of ultrasonography in patients with viral hepatitis-induced HCC and its impact on survival and mortality risk while determining predictors of receiving surveillance before HCC diagnosis. A population-based retrospective cohort analysis of patients with viral hepatitis-induced HCC in Ontario between 2000 and 2010 was performed using data from the Ontario Cancer Registry linked health administrative data. HCC surveillance for 2 years preceding diagnosis was assigned as: i) ≥2 abdominal ultrasound screens annually; ii) 1 screen annually; iii) inconsistent screening; and iv) no screening. Survival rates were estimated using the Kaplan-Meier method and parametric models to correct for lead-time bias. Associations between HCC surveillance and the risk of mortality after diagnosis were examined using proportional-hazards regression adjusting for confounding factors. Overall, 1,483 patients with viral hepatitis-induced HCC were identified during the study period; 20.2% received ≥1 ultrasound screen annually (routine surveillance) for the 2 years preceding diagnosis. The 5-year survival of those receiving routine surveillance was 31.93% (95% CI: 25.77–38.24%) and 31.84% (95% CI: 25.69–38.14%) when corrected for lead-time bias (HCC sojourn time 70 days and 140 days, respectively). This is contrasted with 20.67% (95% CI: 16.86–24.74%) 5-year survival in those who did not undergo screening. In the fully adjusted model, compared to unscreened patients, routine surveillance was associated with a lower mortality risk and a hazard ratio of 0.76 (95% CI: 0.64–0.91) and 0.81 (95% CI: 0.68–0.97), corrected for the respective lead-time bias. Our findings suggest that routine ultrasonography in patients with viral hepatitis is associated with improved survival and reduced mortality risk in a population-based setting. The data emphasizes the importance of surveillance for timely intervention in HCC-diagnosed patients.     

Head-to-Head Comparison of Sirolimus-Eluting Stents versus Paclitaxel-Eluting Stents in Patients Undergoing Percutaneous Coronary Intervention: A Meta-Analysis of 76 Studies

Background

The relative short-, long- and overall-term efficacy and safety of sirolimus-eluting stents (SES, Cypher) compared with paclitaxel-eluting stents (PES, Taxus) in large head-to-head comparisons still remain to be defined.

Methods

We searched Pubmed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) for articles comparing outcomes of interest between SES and PES without language restriction. Short- (≤1 year), long- (>1 year), and overall-term (the longest follow-up of each study) outcomes were evaluated. The primary endpoint was target lesion revascularization (TLR). Other outcomes of interest were target vessel revascularization (TVR), myocardial infarction, all-cause death, cardiac death, stent thrombosis, major adverse cardiac events (MACEs), restenosis and late lumen loss.

Results

Seventy-six studies including more than 15000 patients in randomized controlled trials and over 70000 patients in adjusted observational studies were included. At overall-term follow-up, SES significantly reduced TLR (relative risk [RR]: 0.61; 95% confidence interval [CI]: 0.49–0.76), TVR (RR: 0.67; 95% CI: 0.54–0.83), MACE (RR: 0.79; 95% CI: 0.72–0.87), myocardial infarction (RR: 0.85; 95% CI: 0.73–0.99), in-segment restenosis (RR: 0.50; 95% CI: 0.38–0.65), and in-segment late lumen loss (weighted mean difference [WMD]: −0.19; 95% CI: −0.24–−0.14) in randomized controlled trials compared with PES. In addition, lower rates of death (RR: 0.91; 95% CI: 0.83–1.00), any stent thrombosis (RR: 0.62; 95% CI: 0.45–0.86), definite stent thrombosis (RR: 0.59; 95% CI: 0.45–0.77) were found in patients receiving SES in adjusted observational studies. Largely similar results were found at short- and long-term follow-up, and in patients with diabetes, acute myocardial infarction or long lesions.

Conclusions

SES significantly reduced the short-, long- and overall-term risk of TLR/TVR, MACE, and restenosis, and overall-term risk of myocardial infarction in randomized controlled trials, as compared with PES. Lower rates of death and stent thrombosis were also observed in observational studies in SES-treated patients.