Elevated survivin is associated with a poor response to chemotherapy and reduced survival in lung cancer with malignant pleural effusions

Survivin has been shown to inhibit apoptosis, enhance proliferation and promote angiogenesis. This study aimed to identify diagnostic value of survivin protein in malignant pleural effusion (MPE) and to investigate the prediction of response to chemotherapy and the prognostic role on pleural survivin in lung cancer patients with MPE. Pleural effusion samples were collected from 67 patients with MPE (58 lung cancers; 9 extrathoracic tumors), and from 68 patients with benign conditions (31 with pneumonia; 37 with tuberculosis). Concentrations of pleural fluid survivin, Cyfra 21-1, and carcinoembryonic antigen (CEA) were measured by enzyme-linked immunosorbent assay. The expression profile of survivin in pleural fluid, and its association with survival, were investigated. Survivin levels were significantly elevated in patients with MPE, especially primary lung cancer than in those of benign origin. Survivin, Cyfra 21-1, and CEA varied in diagnostic accuracy for differentiating MPE from benign pleural effusion by 67.5, 68.3, and 93.4%, respectively. Lung cancer patients with MPE who were positive for survivin expression were more refractory to chemotherapy (P = 0.003). Positive for survivin expression was correlated with a reduced overall survival in univariate (P = 0.0001) and multivariate (P = 0.004) analyses. Using the appropriate cut-off points, CEA in pleural fluid has a higher accuracy than other tumor markers, and that survivin has a low diagnostic accuracy for differentiating MPE from benign pleural effusion. Our findings suggest that positive survivin expression may be used as a predictor of a poor response to chemotherapy and shorter survival in lung cancer patients with MPE.     

Evaluation of interferon-gamma release assays for the diagnosis of tuberculosis: an updated meta-analysis

The objective of this investigation was to systematically evaluate the diagnostic accuracy of interferon-gamma release assays (IGRAs) for tuberculosis disease. Both English and Chinese databases were searched for relevant articles through January 2012. We included studies that were restricted to diagnostic applications of IGRAs in patients with active tuberculosis and excluded studies performed in the immune-compromised population. We used Meta-DiSc software to handle the data. We calculated the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and 95?% confidence interval (CI) for each study. We also calculated the pooled sensitivity, specificity, PLR, NLR, DOR, and produced forest plots and summary receiver operating characteristic (SROC) curves. A total of 61 papers (73 studies) were eligible for meta-analysis, including 36 published in English and 25 published in the Chinese language. The overall sensitivity, specificity, PLR, NLR, DOR, and 95?% CI of IGRAs were 0.85 (95?% CI: 0.84–0.86), 0.84 (95?% CI: 0.83–0.85), 7.82 (95?% CI: 6.01–10.19), 0.17 (95?% CI: 0.14–0.21), and 59.27 (95?% CI: 40.19–87.42), respectively. For ten studies evaluating T-SPOT.TB in China, the combined sensitivity, specificity, PLR, NLR, DOR, and 95?% CI were 0.88 (95?% CI: 0.86–0.91), 0.89 (95?% CI: 0.86–0.92), 8.86 (95?% CI: 5.42–14.46), 0.13 (95?% CI: 0.10–0.17), and 88.15 (95?% CI: 41.76–186.07), respectively. The SROC area under the curve (AUC) was 0.9548 (95?% CI: 0.9323–0.9773). Though IGRAs showed good sensitivity and specificity for the detection of tuberculosis in this meta-analysis, the decision to use an IGRA should be based on the local prevalence of the disease and the country guidelines, as well as resources and logistical considerations.     

Diagnostic utility of pleural fluid IFN-gamma in tuberculosis pleural effusion.

Pleural fluid interferon-gamma (IFN-gamma) levels are increased in patients with tuberculosis (TB) pleural effusion. Recent studies from the west have found that estimation of pleural fluid IFN-gamma levels is an excellent diagnostic strategy for these patients. The diagnostic utility of pleural effusion IFN-gamma level estimation has not been evaluated in patients from developing countries, however. This work was carried out to study the diagnostic utility of IFN-gamma level estimation in patients with TB pleural effusion and to define the best cutoff of IFN-gamma for diagnosis TB pleural effusion. We studied 101 patients with pleural effusion. Of these, 64 were found to have a TB etiology, established by means of various conventional modalities. Measurement of pleural fluid IFN-gamma levels was done by ELISA technique. The median value of pleural fluid IFN-gamma levels in patients with TB (1480 pg/ml, range 3-14,000 pg/ml) was significantly higher (p < 0.001) compared with the non-TB group (3 pg/ml, range 0-900 pg/ml). The receiver operator characteristic (ROC) curve for IFN-gamma showed an area under the curve (AUC) value of 0.954, and the best cutoff was computed to be 138 pg/ml. Using this cutoff for IFN-gamma levels in pleural fluid for the diagnosis of TB, sensitivity, specificity, negative predictive value, and positive predictive value were found to be 90.2%, 97.3%, 85.7%, and 98.3%, respectively. Estimation of IFN-gamma levels in pleural fluid is a useful diagnostic modality for TB pleural effusion. A cutoff of 138 pg/ml provides the best sensitivity and specificity for diagnosis of TB.     

Differential diagnostic CYFRA 21-1 level for benign and malignant pleural effusions: a meta-analysis in the Chinese population

Introduction

Many studies have investigated the usefulness of cytokeratin 19 fragments (CYFRA 21-1) in pleural fluid for the differential diagnosis of benign (BPE) and malignant pleural (MPE) effusions. In the present meta-analysis, the reported studies on the diagnosis between CYFRA 21-1 and pleural effusion were assessed to summarize the diagnostic characteristics of CYFRA 21-1 in Chinese patients.

Material and methods

The data sources from the creation of each database up to January 2011 included Medline, Chinese National Knowledge Infrastructure, EMBASE, Cochrane Library, and bibliographies of review and original articles. Through a systematic literature search for publications, the data from 22 studies were summarized based on their discussions on the result of the CYFRA 21-1 assay in pleural effusion and differential diagnosis evaluation in the Chinese population.

Results

A total of 22 studies were available for analysis, and the high CYFRA 21-1 level in MPE was significantly associated with risk for lung cancer (standardized mean difference [SMD] = 1.65, 95% confidence interval [CI] = 1.48–1.82, Z = 18.97, p < 0.00001) compared with BPE. The CYFRA 21-1 level in pleural effusion (13 studies) was significantly higher than that in serum (SMD = 1.10, 95% CI = 0.71–1.48, Z = 5.59, p < 0.00001). The risk for squamous cell carcinoma (SCC) for CYFRA 21-1 was 1.03 (95% CI = 0.64–1.42, Z = 5.15, p < 0.00001) compared with that of adenocarcinoma (8 studies). The sensitivity of CYFRA 21-1 reported in the articles ranged from 46% to 94%, and the specificity ranged from 57% to 100%. The summary measure of the test characteristics derived from the summary receiver operating characteristic curve was 81% for both sensitivity and specificity (17 studies).

Conclusions

The measurement of pleural CYFRA 21-1 is likely to be a useful diagnostic tool for the confirmation of MPE.     

Diagnostic accuracy of immunological methods in patients with tuberculous pleural effusion from Venezuela

In recent years, better diagnostics for tuberculosis (TB) has received increasing attention, especially the diagnosis of tuberculous pleural effusion, which is difficult and at present the main tool in TPE diagnostic is pleural effusion smear and culture, but unfortunately, sensitivities are low, therefore better TPE diagnostic tools are needed. The aim of this study was to find a diagnostic algorithm to assess the progress in TPE diagnostic at the Hospital Vargas de Caracas, that permits identification of the majority of patients, at a satisfactory cost-benefit ratio, evaluating the levels of IFN-gamma and IL-12p40 in pleural effusion and serum, as well as the antibody reactivity in order to compare it with microbiological tests. A total of 60 individuals with pleural effusion were studied; 20 patients with tuberculous pleural effusion (TPE) formed the patient group and 40 patients with non-tuberculous pleural effusion (NTPE) formed the control group. The levels of IFN-gamma and IL-12p40 in effusion and serum and class and subclasses of IgG reactivity to Mycobacterium tuberculosis antigens were measured by ELISA. The utility of these methods for diagnosis of TPE was evaluated using receiver operating characteristic (ROC) curve analysis. The results of the 11 immunological methods evaluated showed that the anti-PPD IgG2 method was able to reach the highest specificity of 95% (CI: 88.3-101.8), positive predictive value (PPV) = 75 (at 30% sensitivity); while that the overall sensitivity of methods was between 95% and 30%, of these, two methods reached higher sensitivities; increased levels of pleural IFN-gamma, with a sensitivity of 95% (CI: 85.5-104.5) with the highest negative predictive value (NPV) = 97, (at 82.5% specificity), followed by decreased levels of serum IL-12p40 with a sensitivity of 95% (CI: 85.5-104.5), NPV = 95.2 (at 50% specificity). In contrast, microbiological methods showed that smear had a sensitivity of only 20%, while smear plus culture had, a sensitivity of 70%. Considering that TPE represents approximately 15 percent of all the TB clinically diagnosed at the Hospital Vargas de Caracas, in those patients with preliminary microbiology negativity in the effusion, the combined analysis of pleural IFN-gamma and anti-PPD IgG2 could represent a fast and effective diagnostic algorithm for improving the diagnosis previous to obtain culture results. In this way treatment against TB could be initiated or the need to cytological and pleural biopsy could be considered.     

Interferon-γ release assays for tuberculous meningitis diagnosis: a meta-analysis

IntroductionTuberculous meningitis (TBM) is still a great challenge to global public health. As conventional diagnostic methods for TBM are unsatisfactory, interferon-γ release assays (IGRAs) have been introduced for TBM diagnosis tentatively. However, the role of IGRAs for diagnosing TBM remains unclear. Thus, we systematically evaluated the diagnostic performance of cerebrospinal fluid (CSF) and peripheral blood (PB) IGRAs in TBM to fill this blank.Material and methodsRelevant studies were systematically searched in both foreign and Chinese databases up to March 2018. Studies in which TBM diagnosis was based on microbiological or clinical criteria were included. The quality of the included studies was assessed through the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Main outcome measures, including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR), were pooled statistically using random effects models. The potential heterogeneity was explored by threshold effect analysis, subgroup analyses and meta-regression. Funnel plots and Egger’s test were used to test the potential publication bias. Statistical analyses were performed using Stata and Meta-DiSc software.ResultsTwenty-six out of 656 publications were eligible for meta-analysis, including 1892 participants in total. The pooled estimates of PB IGRAs for TBM diagnosis are as follows: sensitivity: 0.81 (95% CI: 0.78–0.84); specificity: 0.76 (95% CI: 0.73–0.78); PLR: 4.23 (95% CI: 2.95–6.07); NLR: 0.24 (95% CI: 0.19–0.32) and DOR: 21.06 (11.91-37.24). The corresponding estimates for CSF IGRAs were obtained: sensitivity: 0.81 (95% CI: 0.76–0.85); specificity: 0.89 (95% CI: 0.86–0.92); PLR: 7.87 (95% CI: 4.98–12.46); NLR: 0.19 (95% CI: 0.13–0.29); and DOR: 47.74 (25.02–91.12).ConclusionsThe diagnostic performance of IGRAs is suboptimal. In terms of cost, turn-around time and accessibility, these assays are unsuitable for use as biomarkers for TBM diagnosis.     

Diagnostic accuracy of fecal lactoferrin for inflammatory bowel disease: a meta-analysis

Objective: To do a systematic review using meta-analysis to assess the diagnostic accuracy of fecal lactoferrin (FL) in patients with inflammatory bowel disease (IBD). Methods: We performed a literature review and systematically searched the Medline and EMBASE databases for eligible studies. The quality of the included studies was assessed using the QUADAS tool. The sensitivity, specificity, and other diagnostic indexes of FL were pooled using a random-effects model. Results: Seven studies, involving 1816 patients, met the inclusion criteria. In all studies, the pooled FL sensitivity and pooled specificity were 0.82 (95% confidence interval [CI]: 0.72, 0.89) and 0.95 (95% CI: 0.88, 0.98), respectively. The positive and negative likelihood ratios were 16.63 and 0.18, respectively. The area under the summary receiver-operating characteristic curve (SROC) was 0.95 (95% CI: 0.93, 0.97), and the diagnostic odds ratio was 90.04 (95% CI: 37.01, 219.02). The pooled FL sensitivity and specificity for Crohn’s disease (CD) diagnosis (sensitivity =75%, specificity =100%) was not as good as it was for ulcerative colitis (UC) diagnosis (sensitivity =82%, specificity =100%). Conclusion: FL, as a noninvasive and screening marker, has a high specificity and a modest specificity during the diagnosis of suspected IBD.     

Superoxide dismutase 2 as a marker to differentiate tuberculous pleural effusions from malignant pleural effusions

OBJECTIVES:Our previous study demonstrated that superoxide dismutase levels were higher in tuberculous pleural effusions than in malignant pleural effusions, but that this difference could not be used to discriminate between the two. The objective of the present study was to investigate the levels of superoxide dismutase 2 in pleural effusions and to evaluate the diagnostic significance of pleural effusion superoxide dismutase 2.METHODS:Superoxide dismutase 2 concentrations were determined in pleural effusions from 54 patients with tuberculous pleural effusion and 33 with malignant pleural effusion using an enzyme-linked immunosorbent assay (ELISA) kit. Pleural effusion interferon gamma and tumor necrosis factor alpha levels were also analyzed by ELISA. The Mann-Whitney U test was used to evaluate the significance of differences. Associations between superoxide dismutase 2 concentrations and sex, age and smoking habits were assessed using Spearman''s or Pearson''s correlation coefficient analysis. Receiver operator characteristic analysis was performed to evaluate the value of superoxide dismutase 2 levels in the discrimination of tuberculous pleural effusion from malignant pleural effusion.RESULTS:Superoxide dismutase 2 levels were significantly higher in patients with tuberculous pleural effusion compared with those with malignant pleural effusion (p<0.05). When superoxide dismutase 2 was used to differentiate between tuberculous pleural effusions and malignant pleural effusions, the area under the receiver operator characteristic curve was 0.909 (95% confidence interval, 0.827-0.960; p<0.01). With a cut-off value of 54.2 ng/mL, the sensitivity, specificity, positive likelihood ratio and negative likelihood ratio were 75.8% (95%CI: 57.7-88.9%), 98.1% (95%CI: 90.1-99.7%), 40.91 and 0.25, respectively. Furthermore, significant correlations between pleural effusion superoxide dismutase 2 and interferon gamma (r = 0.579, p<0.01) and between pleural effusion superoxide dismutase 2 and tumor necrosis factor alpha (r = 0.396, p<0.01) were observed.CONCLUSION:Pleural effusion superoxide dismutase 2 can serve as a biomarker for differentiating between tuberculous pleural effusions and malignant pleural effusions. Because of the high correlations of superoxide dismutase 2 with pleural effusion interferon gamma and tumor necrosis factor alpha levels, this marker may act as an inflammatory factor that plays an important role in the development of tuberculous pleural effusion.     

The value of microRNAs as the novel biomarkers for colorectal cancer diagnosis: A meta-analysis

BackgroundNumerous studies have reported that microRNAs (miRNAs) hold great potential as the biomarkers for colorectal cancer (CRC). However, inconsistent results have made it challenging to evaluate their diagnostic performance. Thus, the aim of this meta-analysis was to systematically assess the pooled efficacy of miRNAs for CRC diagnosis.MethodsA search for eligible studies up to October 30, 2019 was conducted using PubMed, Web of Science and EMBASE databases. A random-effects model was used to evaluate the pooled sensitivity and specificity. The summary receiver operator characteristic (SROC) curve and area under the curve (AUC) were calculated to assess the overall diagnostic efficacy.ResultsA total of 3258 CRC patients and 2683 healthy controls were identified in 35 included studies. The overall diagnostic accuracy was as follows: sensitivity, 0.80 [95 % confidence interval (CI) 0.75−0.83]; specificity, 0.80 (95 % CI, 0.75−0.84); positive likelihood ratio (PLR), 4.0 (95 % CI, 3.2−5.0); negative likelihood ratio (NLR), 0.26 (95 % CI, 0.21−0.31); diagnostic odds ratio (DOR), 16 (95 % CI, 11−23); and AUC, 0.87 (95 % CI, 0.83−0.89).ConclusionThe results indicated that miRNAs, particularly serum-derived miRNAs, can serve as the powerful and promising biomarkers for early CRC screening.     

Combined detections of interleukin-33 and adenosine deaminase for diagnosis of tuberculous pleural effusion

Objective: To investigate the diagnostic accuracy of the combination of interleukin-33 (IL-33) and adenosine deaminase (ADA) for differentiating TPE from pleural effusions with the other etiologies. Methods: Pleural effusion samples were collected from 32 TPE patients and 55 non-TPE patients. Pleural levels of IL-33 and ADA were measured by ELISA. The corresponding biochemical indexes were also simultaneously determined. Results: The pleural levels of IL-33 and ADA in the TPE group were significantly higher than those in the non-TPE group. With a cut-off value of 68.3 pg/ml, the sensitivity and specificity for IL-33 were 83.9% and 70.9%, respectively. While for ADA, the sensitivity and specificity were 87.5% and 87.3%, respectively at a cut-off value of 10.25 U/L. Combined use of IL-33 and ADA measurements further increased the sensitivity or specificity. Conclusion: Our study suggests that the applications of new biomarker IL-33, along with ADA, may serve as efficient diagnosis strategies in the management of pleural TB. Further studies at a large scale should be performed to validate our findings.     

The diagnostic usefulness of tumour markers CEA and CA-125 in pleural effusion

Pleural effusion is a common diagnostic problem. The analysis of serum and pleural fluid for tumour markers is widely used as a diagnostic aid in clinical practice. The aim of the present study was to determine the usefulness of simultaneous quantification of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA-125) in distinction of malignant from benign effusion. Data from a total of 78 patients including 53 patients with benign and 25 patients with malignant effusion was evaluated. The cut-off values for differentiating benign from malignant effusions were determined using results obtained from patients with known benign effusions (mean + 2 SD, 95% confidence interval). The cut-off for CEA and CA-125 were 5.1 ng/ml and 1707 IU/ml respectively. CEA assay in pleural fluid had an acceptable sensitivity and good specificity of 64% and 98% respectively. CA-125 had a sensitivity of 36% and specificity of 94%. The combination of the two tumour markers gave a sensitivity of 72% and specificity of 92.4%. We suggest a good clinical strategy may be to begin with CEA measurement (assay specificity 98%); if CEA is below the cut-off value (negative), CA-125 could then be measured to improve the sensitivity of detection of malignant effusions. However, measurement of these tumour markers is not cost effective from the point of view that it does not give information on the type of malignancy present. The latter has to be determined either by histological or cytological study.     

Diagnostic accuracy of enzyme-linked immunosorbent assays (ELISA) to detect anti-skin autoantibodies in autoimmune blistering skin diseases: A systematic review and meta-analysis

BackgroundSystematic reviews and meta-analysis are essential tools to accurately and reliably summarize evidence, and can be used as a starting point for developing practice guidelines for the diagnosis and treatment of patients.AimTo estimate the diagnostic accuracy of enzyme-linked immunosorbent assays (ELISA) to detect anti-BP180 and anti-desmoglein 3 (Dsg3) autoantibodies in the diagnosis of autoimmune blistering skin diseases.MethodsA Medline search of English written articles, published between 1994 and 2011, reporting data on the sensitivity and specificity of diagnostic tests was conducted using the following search terms: “BP180 autoantibodies”, “Dsg3 autoantibodies”, and “enzyme linked immunosorbent assay”. The selected articles have been evaluated according to the quality of the statistical methods used to calculate diagnostic accuracy (definition of cutoff value, use of ROC curves, and selection of control cases).The meta-analysis was performed using a summary ROC (SROC) curve and a random-effect model to independently combine sensitivity and specificity across studies.ResultsThe search yielded 69 publications on BP180 autoantibodies and 178 on Dsg3 autoantibodies. A total of 30 studies met the inclusion criteria: 17 provided data on the assays to detect autoantibodies to BP180 in a sample of 583 patients with bullous pemphigoid (BP), while 13 studies provided data on the assays to search for anti-Dsg3 autoantibodies in a sample of 1058 patients with pemphigus vulgaris (PV). The 17 studies on BP180 autoantibodies yielded a pooled sensitivity of 0.87 (95% confidence interval (CI) 0.85 to 0.89) and a pooled specificity of 0.98 (CI, 0.98 to 0.99). The area under the curve (AUC) for the SROC curve was 0.988, and the summary diagnostic odds ratio was 374.91 (CI, 249.97 to 562.30).The 13 studies on Dsg3 autoantibodies which met the inclusion criteria, yielded a pooled sensitivity of 0.97 (CI, 0.95 to 0.98), and a pooled specificity of 0.98 (CI, 0.98 to 0.99). The AUC for the SROC curve was 0.995 and the summary diagnostic odds ratio was 1466.11 (95% CI, 750.36 to 2864.61).ConclusionsResults of the meta-analysis demonstrated that ELISA tests for anti-BP180 and anti-Dsg3 autoantibodies have high sensitivity and specificity for BP and PV, respectively, and can be used in daily laboratory practice for the initial diagnosis of autoimmune blistering skin diseases.     

Cell-free Mycobacterium tuberculosis DNA test in pleural effusion for tuberculous pleurisy: a diagnostic accuracy study

ObjectivesTuberculous pleurisy (TP) diagnosis remains difficult, with the sensitivity of Xpert MTB/RIF (Xpert) and mycobacterial culture (culture) only about 30–50%. We aimed to assess the diagnostic performance of a cell-free Mycobacterium tuberculosis DNA test (cf-TB) in pleural effusion for TP.MethodsAdults (≥18 years) with suspected TP presenting with pleural effusion were consecutively recruited, and pleural effusion specimens were prospectively collected in Beijing Chest Hospital, Beijing, China. After centrifuging pleural effusion, sediments were used for culture, Xpert and T-SPOT.TB assay, whereas supernatants were used for cf-TB and adenosine deaminase assay. The diagnostic performance was assessed against a composite reference standard.ResultsFrom June 2015 to December 2018, we prospectively evaluated 286 adults with suspected TP. One hundred twenty-two participants were classified as definite TP based on the prespecified composite reference standard. The cf-TB produced a sensitivity of 79.5% (97/122, 95% confidence interval (CI) 72.4– 86.7) for definite TP, which was superior to Xpert (38.5% (29.9–47.2); 47/122; p < 0.001) and culture (27.1% (19.2–34.9); 33/122; p < 0.001). With pleural effusion Xpert and/or culture as the reference standard, cf-TB showed 96.6% (57/59, 95% CI 92.0–100.0) sensitivity, which was also significantly higher than Xpert (79.7%, 95% CI 69.4–89.9; 47/59; p 0.004) and culture (55.9%, 95% CI: 43.3–68.6; 33/59; p < 0.001).ConclusionsThe cf-TB clearly showed improved sensitivity compared with Xpert and culture. We recommend cf-TB as the first-line test for TP diagnosis.     

Serum and Pleural Fluid Procalcitonin in Predicting Bacterial Infection in Patients with Parapneumonic Effusion

This study evaluated the value of procalcitonin (PCT) levels in pleural effusion to differentiate the etiology of parapneumonic effusion (PPE). Forty-one consecutive PPE patients were enrolled and were divided into bacterial and non-bacterial PPE. Blood and pleural effusion samples were collected for PCT measurement on admission and analyzed for diagnostic evaluation. PCT of pleural fluid was significantly increased in the bacterial PPE group (0.24 ng/mL) compared to the non-bacterial PPE group (0.09 ng/mL), but there was no significant difference for serum PCT. A PCT concentration of pleural fluid >0.174 ng/mL (best cut-off value) was considered positive for a diagnosis of bacterial PPE (sensitivity, 80%; specificity, 76%; AUC, 0.84). Pleural effusion PCT in the bacterial PPE is significantly different from those of the non-bacterial PPE and control groups, so the diagnostic use of PCT still warrants further investigation.     

Diagnostic Value and Prognostic Significance of Pleural C-Reactive Protein in Lung Cancer Patients with Malignant Pleural Effusions

Purpose

C-reactive protein (CRP) has been implicated in various inflammatory and advanced malignant states. Increased serum CRP (s-CRP) levels have been shown to be associated with independent prognostic factors for survival in patients with advanced lung cancer. However, only few studies have focused on the role of CRP in pleural effusions. This study aimed to evaluate the diagnostic and prognostic value of pleural CRP (p-CRP) in lung cancer patients with malignant pleural effusion (MPE).

Materials and Methods

Pleural effusion (PE) samples were collected from patients with MPE (68 lung cancers; 12 extrathoracic tumors), and from 68 patients with various benign conditions (31 with pneumonia; 37 with tuberculosis). Concentrations of p- and s-CRP were measured by enzyme-linked immunosorbent assay. CRP level in pleural fluid and its association with survival were examined.

Results

p-CRP levels correlated with s-CRP levels (r=0.82, p<0.0001). For the differential diagnosis of MPE and benign PE, the area under the receiver operating characteristic curve was greater for p-CRP (0.86) than for s-CRP (0.77). High p-CRP expression significantly correlated with shorter overall survival (p=0.006). P-CRP was independent prognostic factor significantly associated with overall survival on multivariated analysis (p=0.0001). The relative risk of death for lung cancer patients with high p-CRP levels was 3.909 (95% confidence interval, 2.000-7.639).

Conclusion

P-CRP is superior to s-CRP in determining pleural fluid etiology. Quantitative measurement of p-CRP might be a useful complementary diagnostic and prognostic test for lung cancer patients with MPE.     

CK19 mRNA在良、恶性胸腔积液的鉴别诊断意义

目的:评价检测CK19 mRNA对良、恶性胸腔积液鉴别诊断的价值.方法:采用RT-PCR方法对43例恶性胸腔积液和57例良性胸腔积液CK19 mRNA进行检测.结果:恶性胸腔积液组中CK19 mRNA阳性率明显高于良性胸腔积液组(P＜0.05).CK19 mRNA检测胸腔积液的敏感性分别是90.7%,特异性都是70.2%,准确性是79.0%.结论:胸腔积液中CK19 mRNA测定可作为鉴别诊断恶性胸腔积液的重要方法.     

Diagnostic accuracy of adenosine deaminase for tuberculous peritonitis: a meta-analysis

Introduction

Tuberculous peritonitis remains a diagnostic challenge for clinicians. Many studies have investigated the usefulness of adenosine deaminase (ADA) in ascites for the diagnosis of tuberculous peritonitis; however, the overall diagnostic accuracy of ADA for tuberculous peritonitis remains unclear. The aim of the present meta-analysis was to determine the overall accuracy of ADA measurements in the diagnosis of tuberculous peritonitis.

Material and methods

We performed a systematic search in PubMed and Embase to identify published studies that evaluated the diagnostic role of ADA for tuberculous peritonitis. Quality was assessed according to standardized Quality Assessment of Diagnostic Accuracy Studies criteria. Sensitivity, specificity and other measures of accuracy of ADA assay in order to diagnose tuberculous peritonitis were pooled using random effects models. Summary receiver operating characteristic curve (SROC) was used to summarize overall test performance.

Results

Sixteen studies met inclusion criteria for the present meta-analysis. The pooled sensitivity and specificity for diagnosing tuberculous peritonitis were 0.93 (95% CI: 0.89–0.95) and 0.96 (95% CI: 0.94–0.97), respectively. The positive likelihood ratio was 15.80 (95% CI: 10.87–22.95), negative likelihood ratio was 0.09 (95% CI: 0.05–0.16) and diagnostic odds ratio was 249.28 (95% CI: 113.11–549.39). The area under the SROC was 0.98.

Conclusions

Ascitic ADA determination is a relatively sensitive and specific test for the diagnosis of tuberculous peritonitis. Measurement of ADA in ascites is thus likely to be a useful diagnostic method for tuberculous peritonitis.     

Interferon Gamma Release Assays for Diagnosis of Pleural Tuberculosis: a Systematic Review and Meta-Analysis

The role of interferon gamma release assays (IGRAs), although established for identifying latent tuberculosis, is still evolving in the diagnosis of active extrapulmonary tuberculosis. We systematically evaluated the diagnostic performance of blood- and pleural fluid-based IGRAs in tuberculous pleural effusion (TPE). We searched the PubMed and Embase databases for studies evaluating the use of commercially available IGRAs on blood and/or pleural fluid samples for diagnosing TPE. The quality of the studies included was assessed through the QUADAS-2 tool. The pooled estimates of sensitivity and specificity with 95% confidence intervals (95% CI) were generated using a bivariate random-effects model and examined using forest plots and hierarchical summary receiver operating characteristic (HSROC) curves. Indeterminate IGRA results were included for sensitivity calculations. Heterogeneity was explored through subgroup analysis and meta-regression based on prespecified covariates. We identified 19 studies assessing the T.SPOT.TB and/or QuantiFERON assays. There were 20 and 14 evaluations, respectively, of whole-blood and pleural fluid assays, involving 1,085 and 727 subjects, respectively. There was only one good-quality study, and five studies used nonstandard assay thresholds. The pooled sensitivity and specificity for the blood assays were 0.77 (95% CI, 0.71 to 0.83) and 0.71 (95% CI, 0.65 to 0.76), respectively. The pooled sensitivity and specificity for the pleural fluid assays were 0.72 (95% CI, 0.55 to 0.84) and 0.78 (95% CI, 0.65 to 0.87), respectively. There was considerable heterogeneity; however, multivariate meta-regression did not identify any covariate with significant influence. There was no publication bias for blood assays. We conclude that commercial IGRAs, performed either on whole-blood or pleural fluid samples, have poor diagnostic accuracy in patients suspected to have TPE.     

Diagnostic value of circular RNAs in colorectal cancer: A systematic review and meta-analysis

PurposeMounting studies has revealed that circular RNAs (circRNAs) play a key role in tumorigenesis and might serve as promising biomarkers for cancer diagnosis. However, the diagnostic value of circRNAs in colorectal cancer (CRC) remains to be precisely elucidated.MethodsAll relevant literatures were searched using Cochrane Library, PubMed, Web of Science, EMBASE, CNKI, and WanFang databases up to June 2019. The quality of eligible studies was assessed in accordance with the Quality Assessment of Diagnostic Accuracy Studies-2 system. The summary receiver operator characteristic curve (SROC) and area under SROC (AUC) were applied for the quantitative assessment of diagnostic performance. Threshold effect, subgroup analysis, and meta-regression were adopted to explore the sources of heterogeneity. Deeks’ funnel plot and sensitivity analysis were conducted to examine the publication bias and stability of meta-analysis, respectively.ResultsA total of 13 eligible studies involving 2190 subjects and 14 different kinds of circRNAs were enrolled. The pooled sensitivity, specificity, and AUC were 0.78 [95% confidential interval (CI): 0.70-0.84], 0.71 (95% CI: 0.65-0.76), and 0.80 (95% CI: 0.76-0.83), respectively. Subgroup analysis showed that studies involving ≥ 100 cases had higher sensitivity but lower specificity than those involving < 100 cases. Meta-regression revealed that sample size might be the potential source of heterogeneity. Sensitivity analysis and Deeks’ funnel plot indicated that our results were relatively robust and had no publication bias.ConclusionCircRNAs possess relatively moderate diagnostic accuracy and might serve as potential diagnostic biomarkers for colorectal cancer. Future large-scale studies are needed to confirm the diagnostic value of circRNAs.     

Role of the Neutrophil-Lymphocyte Ratio in the Differential Diagnosis of Exudative Pleural Effusion

OBJECTIVES:Pleural effusion is a common diagnostic and clinical problem. The differential diagnosis of pleural effusion may be difficult and may require several procedures, including invasive ones. Certain studies have investigated biochemical parameters to facilitate the diagnosis of exudative pleural effusion; however, it remains a challenging problem in clinical practice. We aimed to investigate the potential role of the neutrophil-lymphocyte ratio, which can be easily obtained by determining the cell count of the pleural fluid, in the differential diagnosis of exudative pleural effusion.METHODS:Records from patients who underwent thoracentesis and pleural fluid analysis between May 1, 2013, and March 1, 2015, were obtained from the electronic database of our hospital. The patients who met the inclusion criteria were divided into five groups according to their diagnosis: malignant pleural effusion, para-malignant pleural effusion, para-pneumonic effusion, tuberculosis-related effusion or other. The neutrophil-lymphocyte ratio value was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. The patient groups were compared according to the given parameter.RESULTS:A total of 465 patients who met the inclusion criteria among 1616 patients with exudative pleural effusion were included in the study. The mean neutrophil-lymphocyte ratio value was significantly lower in tuberculosis-related pleural effusion compared to malignant, para-pneumonic and para-malignant effusions (p=0.001, p=0.001, p=0.012, respectively). The areas under the curve for tuberculosis pleurisy compared to malignant, para-pneumonic and para-malignant effusions were 0.38, 0.36, and 0.37, respectively. Lower cut-off values had higher sensitivity but lower specificity for tuberculosis pleurisy, while higher cut-off values had higher specificity but lower sensitivity for this condition.CONCLUSION:The pleural fluid neutrophil-lymphocyte ratio, which is an inexpensive, reproducible, and easily calculated hematological parameter, may facilitate the differential diagnosis of pleural effusion.