Determination of the cause of malignant pleural effusions is important for treatment and management, especially in cases of unknown primaries. There are limited biomarkers available for prediction of the cause of malignant pleural effusion in clinical practice. Hence, we evaluated pleural levels of five tumor biomarkers (CEA, AFP, CA125, CA153 and CA199) in predicting the cause of malignant pleural effusion in a retrospective study. Kruskal-Wallis or Mann-Whitney U tests were carried out to compare levels of tumor markers in pleural effusion among different forms of neoplasia - lung squamous cell carcinoma, adenocarcinoma, or small cell carcinoma, mesothelioma, breast cancer, lymphoma/leukemia and miscellaneous. Receiver operator characteristic analysis was performed to evaluate sensitivity and specificity of biomarkers. The Kruskal-Wallis test showed significant differences in levels of pleural effusion CEA (P0.05), among the seven groups. Receiver operator characteristic analysis showed that, compared with other four tumor markers, CA153 was the best biomarker in diagnosing malignant pleural effusions of lung adenocarcinoma (area under curve (AUC): 0.838 (95%confidence interval: 0.787, 0.888); cut-off value: 10.2U/ ml; sensitivity: 73.2% (64.4-80.8)%, specificity: 85.2% (77.8-90.8)%), lung squamous cell carcinoma (AUC: 0.716 (0.652, 0.780); cut-off value: 14.2U/ml; sensitivity: 57.6% (50.7-64.3)%, specificity: 91.2% (76.3-98.0)%), and small-cell lung cancer (AUC: 0.812 (0.740, 0.884); cut-off value: 9.7U/ml; sensitivity: 61.5% (55.0-67.8)%, specificity: 94.1% (71.2-99.0)%); CEA was the best biomarker in diagnosing MPEs of mesothelioma (AUC: 0.726 (0.593, 0.858); cut-off value: 1.43ng/ml; sensitivity: 83.7% (78.3-88.2)%, specificity: 61.1% (35.8-82.6)%) and lymphoma/leukemia (AUC: 0.923 (0.872, 0.974); cut-off value: 1.71ng/ml; sensitivity: 82.8% (77.4-87.3)%, specificity: 92.3% (63.9-98.7)%). Thus CA153 and CEA appear to be good biomarkers in diagnosing different causes of malignant pleural effusion. Our findings implied that the two tumor markers may improve the diagnosis and treatment for effusions of unknown primaries.

Currently, there is limited data on the risk factors associated with treatment delay in tuberculous meningitis (TBM). This study aimed to assess the duration of delay in the treatment TBM and to investigate its determinants. During the period from September 2009 to February 2016, a retrospective cohort study of consecutive TBM patients admitted to our hospital was conducted to determine the risk factors associated with treatment delay in TBM. Treatment delay duration was defined as the time interval from onset of symptoms (by patient recall) to initiation of treatment and was stratified into two categories: ≤ 20 days, >20 days (median delay day is 20 days). Data collected included demography, comorbidity, cerebrospinal fluid (CSF) examinations and others. Univariable and multivariable logistic regression analysis was used to evaluate the determinants of treatment delay. A total of 161 TBM patients were included in our study, all were confirmed by CSF mycobacterial culture. The median treatment delay for all patients included in the study was 20 days [interquartile range, 14–60 days]. Multivariate analysis revealed that age (≤21 years old, OR = 0.202, 95% CI: 0.079, 0.521), fever (OR = 0.414, 95% CI: 0.180, 0.952), and headache (OR = 0.204, 95% CI: 0.095, 0.442) had significantly lower risk for treatment delay, while multiple healthcare contact (>3 times) (OR = 3.938, 95% CI: 1.326, 11.691) as well as CSF chloride (>111 mmol/L) (OR = 2.479, 95% CI: 1.143, 5.377) had significantly higher risk of the delay. Our findings indicate that multiple healthcare contact and high CSF chloride predict the risk of long delay, while young age, fever and headache are associated with short delay. Maintained focus on awareness of TBM in the population and in healthcare systems, and continuous implementation of diagnostic methods for TBM to detect the disease early, may reduce the mortality and morbidity.

Tuberculous empyema (TE) is associated with high mortality and morbidity. In the retrospective cohort study, we aimed to find risk factors for TE among pleural tuberculosis (TB) patients. Between July 2011 and September 2015, all culture-confirmed pleural TB patients (474 cases) were enrolled in our study. Empyema was defined as grossly purulent pleural fluid. Demographic and epidemiological data were collected for further analysis. Multivariate logistic regression analysis was used to evaluate risk factors of TE in pleural TB, age–adjusted odds ratio (OR) and 95% confidence interval (CI) were calculated to show the risk. The mean age was 35.7 ± 18.1 years old, males comprised 79.1% of the participants (375 cases). Forty-seven patients (9.9%) were multidrug-resistant TB (MDR-TB), 29 (6.1%) had retreatment TB, 26 (5.5%) had diabetes mellitus. The percentage of empyema patients was 8.9% (42 cases). Multivariate analysis revealed that male (adjusted OR = 4.431, 95% CI: 1.411, 13.919), pleural adenosine deaminase (ADA, >88 U/L) (adjusted OR = 3.367, 95% CI: 1.533, 7.395) and white blood cell (WBC, >9.52 10⁹/L) (adjusted OR = 5.763, 95% CI: 2.473, 13.431) were significant risk factors for empyema in pleural TB, while pulmonary TB (adjusted OR = 0.155, 95% CI: 0.072, 0.336) was the protective factor for the patients. TE remains a serious threat to public health in China. Male sex is a significant risk factor for TE while the presence of pulmonary TB is protective, and high levels of pleural ADA and WBC count could aid in early diagnosis of TE. This finding would help towards reducing the mortality and morbidity associated with TE.

Background: Interferon γ release assays (IGRAs) are widely used for diagnosis of latent tuberculosis infection. However, with repeated testing, IGRA transformation (conversion or reversion) may be detected and is challenging to interpret. We reviewed the frequency of and risk factors for IGRA transformation. Methods: We screened public databases for studies of human participants that reported the frequency of IGRA transformation. We extracted study and participant characteristics, details of IGRA testing and results. We calculated the pooled frequency of IGRA transformation (and transient transformation) and examined associated risk factors. Results: The pooled frequency of IGRA conversion or reversion from 244 studies was estimated at 7.3% (95% confidence interval [CI], 6.1%–8.5%) or 22.8% (20.1%–25.7%), respectively. Transient conversion or reversion were estimated at 46.0% (95% CI, 35.7%–56.4%) or 19.6% (9.2%–31.7%) of conversion or reversion events respectively. Indeterminate results seldom reverted to positive (1.2% [95% CI, .1%–3.5%]). IGRA results in the borderline-positive or borderline-negative range were associated with increased risk of conversion or reversion (pooled odds ratio [OR] for conversion, 4.15 [95% CI, 3.00–5.30]; pooled OR for reversion, 4.06 [3.07–5.06]). BCG vaccination was associated with decreased risk of conversion (OR, 0.70 [95% CI, .56–.84]), cigarette smoking with decreased risk of reversion (0.44 [.06–.82]), and female sex with decreased risk of either conversion or reversion (OR for conversion, 0.66 [.58–.75]; OR for reversion, 0.46 [.31–.61]). Conclusions: IGRA conversion is less common than reversion, and frequently transient. Research is needed to determine whether individuals with reversion would benefit from tuberculosis-preventive treatment. Retesting of people with indeterminate results is probably not indicated, because indeterminate results seldom revert to positive.

A negative interferon-γ release assay (IGRA) result might inappropriately lower the clinical suspicion for childhood tuberculosis (TB) and result in delayed treatment initiation. However, the risk factors associated with false-negative IGRA results in children remain unclear. Between May 2012 and January 2018, 156 culture-confirmed childhood TB patients who had received T-SPOT.TB test were included. Data, including demographic information and clinicopathological variables, were collected via questionnaires. Univariate and multivariate logistic regression analyses were performed to estimate the odds ratio (OR) and corresponding 95% CI of risk factors associated with false-negative T-SPOT.TB results. The positive rate of T-SPOT.TB test was 85.9% in childhood TB patients. Multivariate analysis revealed that younger age (≤ 9 years; OR = 4.782; 95% CI: 1.689, 13.539), weight for age (z-score > 0.37; OR = 4.256; 95% CI: 1.458, 12.428), and hypoproteinemia (total protein ≤ 68.4 g/L; OR = 7.131; 95% CI: 1.864, 27.271) were risk factors for false-negative T-SPOT.TB results in childhood TB. Younger age, overweight, and hypoproteinemia were found to be associated with false-negative T-SPOT.TB results in childhood TB. Health care professionals should consider these risk factors when evaluating suspected childhood TB with negative T-SPOT.TB results.

The interferon-gamma release assay (IGRA) is more specific than the tuberculin skin test to discriminate between tuberculosis (TB) and nontuberculous mycobacterial (NTM) diseases. Here we performed a retrospective study to evaluate the performance of the T-SPOT.TB in patients with NTM diseases. Between March, 2013 and Nov, 2015, a total of 58 patients with NTM diseases had a T-SPOT.TB performed were enrolled, 30 patients had definite NTM diseases, 28 had probable diseases. Their clinicopathological characteristics were reviewed and analyzed. Cultures for mycobacteria were performed. The indirect proportion method with Löwenstein–Jensen (L-J) medium was used for first-line drug susceptibility test. T-SPOT.TB assay was performed according to the manufacturer’s instructions. Data were expressed as mean ± standard deviation (continuous variables) and as numbers and percentages (categorical variables). The χ2 test was used for comparisons between proportions. The average age was 51.8 ± 16.1 years (range 10 to 77 years), 58.6% (34/58) were male. 16.4% (9/55) were TB-PCR positive. 34 (58.6%) isolates were Mycobacterium intracellulare, ten (17.2%) were Mycobacterium chelonae and seven (12.1%) were Mycobacterium fortuitum. Fifty-two (89.7%) patients were NTM lung disease, five (8.6%) were pleural disease, and one (1.7%) lymphadenitis. The total positivity of T-SPOT.TB was 53.4% (31/58) among the whole group (probable and definite). For probable cases, the T-SPOT.TB assay was positive in 53.5% (15/28); for definite cases, 16 (53.3%) of 30 definite cases were positive. There was no statistical difference in the positivity rate between them (P < 0.01). In the study, we showed that a significant portion of NTM diseases were T-SPOT.TB positive in China. Although T-SPOT.TB is useful diagnostic method for differentiating TB from NTM diseases, in China, the IGRA assay show limited value in the discrimination. In addition, further research is needed to investigate the association between TB infection and treatment for NTM patients.