Circulating CEA-dNLR score predicts clinical outcome of metastatic gallbladder cancer patient.

BACKGROUND: Cancer-related inflammation promotes gallbladder tumorigenesis and metastasis of gallbladder cancer (mGBC). The levels of circulating inflammatory-related cell and protein as well as the ratios of them may imply the severity of chronic inflammation in GBC patients, and all of them are candidate prognostic biomarkers for mGBC. MATERIALS AND METHODS: In our study, pre-treatment circulating immune cell, fibrinogen (Fib), albumin (Alb), and pre-albumin (pAlb) were detected in 220 mGBC patients, and we calculated neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), Alb-to-Fib ratio (AFR), and Fib-to-pAlb ratio (FPR) replying on the detection. Three years' follow-up was carried out in those patients, and we investigated the possible associations between those biomarkers and three years' overall survival (OS) of these patients using X-tile software, Kaplan-Meier curve, Cox regression, and time-dependent receiver operating characteristics (ROC). RESULTS: Our results showed that OS of the patients with high pAlb and LMR was significantly superior to the cases with the low biomarkers, respectively. However, survival of the cases with high CEA, dNLR, and FPR was significantly inferior to the patients with low levels of those biomarkers. Area under the curve (AUC) of time-dependent ROC of CEA and dNLR was higher than pAlb, LMR, and FPR, respectively. Additionally, higher CEA-dNLR score (adjusted HR = 3.09, 95% CI = 1.01-4.51 for the score one; adjusted HR = 4.99, 95% CI = 2.32-7.21 for the score two) was significantly associated with reduced survival of the patients, and AUC of the score for predicting clinical outcome of mGBC patients was 0.756, and it was significantly higher than the single CEA and dNLR, respectively. CONCLUSION: Our findings implied that pretreatment CEA-dNLR score was superior to the other biomarkers to predict OS of mGBC patients, and it was an independent prognostic factor for the disease.

Evaluation of the microscopic observation drug susceptibility assay for the rapid detection of MDR-TB and XDR-TB in China: a prospective multicentre study.

OBJECTIVES: To perform a multicentre study evaluating the performance of the microscopic observation drug susceptibility (MODS) assay for the detection of MDR-TB and XDR-TB in high-burden resource-limited settings. METHODS: We performed a prospective diagnostic accuracy study of drug-resistant TB suspects from outpatient and inpatient settings in five laboratories in China. Sputum was tested by smear microscopy, liquid [mycobacterial growth indicator tube (MGIT)] culture and the MODS assay at each site. Drug susceptibility testing (DST) was by MODS and an indirect 1% proportion method. The reference standard for Mycobacterium tuberculosis detection was growth on MGIT culture; the 1% proportion method was the reference standard for rifampicin, isoniazid, ofloxacin, kanamycin and capreomycin DST. RESULTS: M. tuberculosis was identified by reference standard culture among 213/532 (40.0%) drug-resistant TB suspects. Overall MODS sensitivity for M. tuberculosis detection was 87.8%-94.3% and specificity was 96.8%-100%. For drug-resistant TB diagnosis, excellent agreement was obtained for all drugs tested at the majority of sites. The accuracy was 87.1%-96.7% for rifampicin, 87.1%-93.3% for isoniazid, 92.7%-100% for ofloxacin, 90.9%-100% for kanamycin and 90.2%-100% for capreomycin. The median time to culture positivity was significantly shorter for MODS than for the MGIT liquid culture (8 days versus 11 days, P<0.001). The contamination rate ranged between 2.1% and 5.3%. CONCLUSIONS: In the study settings, MODS provided high sensitivity and specificity for rapid diagnosis of TB and drug-resistant TB. We consider it to have a strong potential for timely detection of MDR-TB and XDR-TB in high-burden resource-limited settings.

[Rapid diagnosis of pleural tuberculosis by Xpert MTB/RIF assay].

OBJECTIVE: Early diagnosis of pleural tuberculosis (TB) is particularly difficult. The aim of this study was to investigate the diagnostic accuracy of the Xpert MTB/RIF (Xpert) assay using pleural biopsy and pleural fluid specimens in patients with suspected pleural TB negative for sputum acid-fast bacilli (AFB) smear. METHODS: In this study, 134 sputum smear-negative suspected pleural TB patients were selected. Paired pleural fluid and pleural biopsy specimens were tested for Mycobacterium tuberculosis by standard smear-microscopy, Lowenstein-Jensen and mycobacterial growth indicator tube (MGIT) culture, and the Xpert assay. Mycobacterial culture from pleural biopsy specimens were used as a reference standard for sensitivity and specificity calculations. Detection of rifampicin resistance was compared to the MGIT method. RESULTS: The sensitivity of the Xpert assay using pleural biopsy specimens for the diagnosis of pleural TB was 85.5% (47/55), and the specificity was 97.2% (69/71). The sensitivity and specificity of the Xpert assay in pleural fluid were 43.6% (24/55) and 98.6% (70/71), respectively. The Xpert assay correctly identified 90.0% (10/11) of phenotypic rifampicin-resistant cases and 93.9% (31/33) of phenotypic rifampicin-susceptible cases. CONCLUSION: The Xpert assay on pleural biopsy specimens may provide an accurate diagnosis of pleural TB in patients who had a negative AFB smear.

Rapid diagnosis of pleural tuberculosis by Xpert MTB/RIF assay using pleural biopsy and pleural fluid specimens.

BACKGROUND: Early pleural tuberculosis (TB) diagnosis is particularly difficult. The aim of this study was to investigate the diagnostic accuracy of the Xpert MTB/RIF (Xpert) (Cepheid, Sunnyvale, CA) assay using pleural biopsy and pleural fluid specimens in patients with suspected pleural TB but who had a negative sputum acid-fast bacilli (AFB) smear. MATERIALS AND METHODS: In this study, 134 sputum smear-negative suspected pleural TB patients were selected. Paired pleural fluid and pleural biopsy specimens were tested for Mycobacterium tuberculosis by standard smear-microscopy, Lowenstein-Jensen and mycobacterial growth indicator tube (MGIT) culture, and the Xpert assay. Mycobacterial culture from pleural biopsy specimens was used as a reference standard for sensitivity and specificity calculations. Detection of rifampicin resistance was compared with the MGIT method. RESULTS: Of 126 evaluable patients, 55 received a diagnosis of pleural TB. The sensitivity of the Xpert assay using pleural biopsy specimens for the diagnosis of pleural TB was 85.5%, and specificity was 97.2%. The sensitivity and specificity of the Xpert assay in pleural fluid were 43.6% and 98.6%, respectively. The Xpert assay correctly identified 90.0% of phenotypic rifampicin-resistant cases and 93.9% of phenotypic rifampicin-susceptible cases. CONCLUSION: The Xpert assay on pleural biopsy specimens may provide an accurate diagnosis of pleural TB in patients who had a negative AFB smear.

Multicentre laboratory validation of the nitrate reductase assay using liquid medium for the rapid detection of multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis.

To perform a multicentre study evaluating the performance of the nitrate reductase assay (NRA) using liquid medium for the detection of multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis and to establish the MICs and critical concentrations of rifampicin, isoniazid, ofloxacin, amikacin, kanamycin and capreomycin. The study was carried out in three phases. Phase I determined the MIC of each drug. Phase II established the critical concentration of each drug. Phase III validated critical concentrations for the six drugs tested by the NRA using liquid medium compared with the agar proportion method or MGIT 960 system at each site. The critical concentrations for the six drugs used in the NRA are as follows: rifampicin, 1 mg/L; isoniazid, 0.2 mg/L; ofloxacin, 2 mg/L; amikacin, 2 mg/L; kanamycin, 5 mg/L; capreomycin, 2.5 mg/L. Phase III: Excellent agreement was obtained for all drugs tested at the majority of sites. The accuracy was 97%-100% for rifampicin, 96.8%-99.2% for isoniazid, 98%-100% for ofloxacin, 96.8%-98.5% for amikacin, 96.4%-99.5% for kanamycin and 96.8%-100% for capreomycin. Results for NRA using liquid medium were obtained in a median time of 7 days. NRA performed in liquid medium offers a rapid, economical and feasible method for detection of M. tuberculosis resistance to first- and second-line drugs in resource-limited settings.

[Advances in isolation and enrichment of circulating tumor cells in microfluidic chips].

The research of circulating tumor cells (CTCs) has drawn increasing attention in recent years, because its potential value in the early diagnosis of cancers, management of clinical treatment, development of personalized medicine, and exploring the mechanism of metastasis. However, the difficulty in using CTCs lies in their extremely low concentrations. Recently, microfluidic devices have shown the potential to efficiently isolate and detect rare CTCs in cancer patients. A variety of on-chip blood analysis has been demonstrated by several groups. The advantages of microfluidics include low cost, short reaction times, high throughput, and ease of use. Recently, a variety of microfluidic devices have been developed to CTCs isolation and enrichment which can realize high capture efficiency, high purity and high throughput. In this article, we review some of the recent works in microfluidic CTCs isolation and enrichment devices and discuss in what field should be done next based on our researches.

Rapid isolation of cancer cells using microfluidic deterministic lateral displacement structure.

This work reports a microfluidic device with deterministic lateral displacement (DLD) arrays allowing rapid and label-free cancer cell separation and enrichment from diluted peripheral whole blood, by exploiting the size-dependent hydrodynamic forces. Experiment data and theoretical simulation are presented to evaluate the isolation efficiency of various types of cancer cells in the microfluidic DLD structure. We also demonstrated the use of both circular and triangular post arrays for cancer cell separation in cell solution and blood samples. The device was able to achieve high cancer cell isolation efficiency and enrichment factor with our optimized design. Therefore, this platform with DLD structure shows great potential on fundamental and clinical studies of circulating tumor cells.