Lih-Yu Chang

Evaluating pleural ADA, ADA2, IFN-γ and IGRA for diagnosing tuberculous pleurisy

OBJECTIVE Conventional methods for diagnosing tuberculous pleurisy (TB pleurisy) are either invasive or have a long turn-around-time. Performances of pleural adenosine deaminase (ADA), ADA2, interferon-gamma (IFN-γ), and interferon-gamma release assays (IGRA) as diagnostic tools for TB pleurisy were evaluated. METHODS Eighty-eight patients with lymphocyte-predominant pleural exudates between June 2010 and March 2011, including 31 with clinically diagnosed TB pleurisy, were prospectively studied. Pleural ADA and ADA2 activity were measured by colorimetric method, IFN-γ levels by enzyme-linked immuno-sorbent assay, and IGRA by enzyme-linked immuno-spot (T-SPOT.TB) assay. RESULTS Pleural ADA, ADA2, and IFN-γ levels, but not the proportion of positive T-SPOT.TB assay, were significantly higher in patients with TB pleurisy than in those without TB pleurisy. The area under the receiver-operating-characteristic (ROC) curve was 0.920, 0.893, 0.875, and 0.544 for IFN-γ, ADA2, ADA, and T-SPOT.TB assay, respectively. The combination of ADA ≥ 40 IU/L and IFN-γ ≥ 75 pg/mL yielded a specificity of 100%. CONCLUSIONS Pleural ADA, ADA2 and IFN-γ, but not T-SPOT.TB assay, are all sensitive and specific for TB pleurisy. In patients with lymphocyte-predominant pleural exudates, ADA ≥ 40 IU/L and IFN-γ ≥ 75 pg/mL in pleural effusion imply a very high probability of TB pleurisy.

Severe lymphopenia is associated with elevated plasma interleukin-15 levels and increased mortality during severe sepsis.

ABSTRACT Sepsis-related mortality has been found increased in RAG-1 knockout mice. However, in patients admitted to medical intensive care units, it is unknown whether severe lymphocyte depletion at admission is associated with increased interleukin (IL)-7 and IL-15 levels in circulation, and increased mortality. We prospectively enrolled 92 patients who were admitted to medical intensive care units for severe sepsis or septic shock. At admission, 24 patients (26.1%) had severe lymphopenia, defined as lymphocyte counts of less than 0.5 × 103/&mgr;L. Severe lymphopenia was associated with significantly higher plasma levels of tumor necrosis factor &agr;, IL-6, IL-8, and IL-10 and was also independently associated with 28-day mortality (adjusted hazard ratio, 3.532; 95% confidence interval, 1.482−8.416; P = 0.004). The levels of plasma IL-15, but not IL-7, were increased modestly in patients with severe lymphopenia compared with those without (median, 12.2 vs. 6.4 pg/mL; P = 0.005). The elevated plasma IL-15 levels were contrarily associated with significantly decreased B-cell lymphoma 2 mRNA expression in peripheral blood mononuclear cells. In conclusion, severe lymphopenia was associated with increased mortality in patients with severe sepsis. We found that patients with sepsis with severe lymphopenia had down-regulated B-cell lymphoma 2 mRNA expression in peripheral blood mononuclear cells, despite increased plasma IL-15 concentrations. Whether IL-7 and IL-15 are insufficient in patients with severe lymphopenia during severe sepsis warrants further investigations.

Plasma Biomarkers Can Predict Treatment Response in Tuberculosis Patients: A Prospective Observational Study.

AbstractDespite numerous studies, there has been little progress in the use of biomarkers for predicting treatment response in patients with tuberculosis (TB).Patients with culture-confirmed pulmonary TB between 2010 and 2014 were prospectively recruited. Blood samples were taken upon diagnosis and 2 months after the start of standard anti-TB treatment. A pilot study utilizing measurement of TB-antigen-stimulated cytokines was conducted to select potential biomarkers for further testing. Outcome was defined as persistent culture positivity at 2 months into treatment.Of 167 enrolled patients, 26 had persistent culture positivity. RANTES, IL-22, MMP-8, IL-18, MIG, and Granzyme A were selected as potential biomarkers. For predicting persistent culture positivity, receiver-operating characteristics (ROC) analysis showed that initial RANTES (AUC: 0.725 [0.624–0.827]) and 2-month MMP-8 (AUC: 0.632 [0.512–0.713]) had good discriminative ability. Using a logistic regression model, low initial RANTES level (<440 pg/mL), initial smear positivity, and high 2-month MMP-8 level (>3000 pg/mL) were associated with persistent culture positivity. Low initial RANTES level and initial smear positivity had a positive predictive value of 60% (12/20) for persistent culture positivity, compared with 4% (3/75) among patients with high RANTES level and smear negativity upon diagnosis. In the 72 patients with either low RANTES/smear negativity or high RANTES/smear positivity upon diagnosis, the 2-month MMP-8 level had a positive and negative predictive value of 24 and 94%, respectively, for 2-month culture status.Aside from an initial sputum smear status, serum RANTES level at diagnosis and MMP-8 level at 2 months of treatment may be used to stratify risk for culture persistence.

Learning curve and advantages of endobronchial ultrasound‐guided transbronchial needle aspiration as a first‐line diagnostic and staging procedure

Endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) is now the standard for mediastinal lymph node staging of lung cancer. Training and maintenance of technical skills is very important in order to apply new techniques in clinical use.

Current advances of endobronchial ultrasonography in the diagnosis and staging of lung cancer

The diagnosis and staging of patients with lung cancer has relied on tissue sampling. Endobronchial ultrasound (EBUS) is a minimally invasive procedure for the rapid and safe acquisition of tissue and can be done easily and repeatedly. EBUS transbronchial needle aspiration (TBNA) is now the standard for diagnosis of mediastinal and hilar lymphadenopathy and should be considered in patients who have a high probability of lymph node metastases without systemic involvement. EBUS also provides guidance for biopsy of peripheral lung lesions. Recent advances of EBUS with new techniques help to improve the diagnostic yield and decrease the complication rate and total procedure time.

Twelve-dose weekly rifapentine plus isoniazid for latent tuberculosis infection: A multicentre randomised controlled trial in Taiwan

Treatment of latent tuberculosis (TB) infection (LTBI) effectively prevents its progression to active TB. However, long treatment duration and drug-related hepatotoxicity limit the effectiveness of the 9-month daily isoniazid (9H). Data on the 3-month weekly rifapentine plus isoniazid (3 HP) in Asian populations are currently unavailable. We prospectively randomised the LTBI contacts aged ≥12 years with positive tuberculin skin test into 9H and 3 HP groups in four hospitals between January 2014 and May 2016 in Taiwan. The primary and secondary outcomes were treatment completion rate and adverse drug reactions (ADRs), respectively. Overall, 263 participants with LTBI were randomised into the 3 HP (n = 132) and 9H groups (n = 131); 14 (10.6%) and 29 (22.1%) participants in the 3 HP and 9H groups, respectively, discontinued therapy (p = 0.011). Discontinuation rates owing to ADRs were 9.1% (3 HP) and 5.3% (9H) (p = 0.241). Clinically relevant hepatotoxicity was more common in the 9H than in the 3 HP group (5.3% vs. 1.5%; p = 0.103), whereas systemic drug reaction was more common in the 3 HP than in the 9H group (3.8% vs. 0%; p = 0.060). Women had a significantly higher rate of Grade II fever than men (13.7% vs. 1.2%; p = 0.003). Compared with the 9H regimen, the 3 HP regimen had a higher completion rate with lower hepatotoxicity and well-tolerated ADR. CLINICAL TRIALS REGISTRATION number NCT02208427.

Differentiating metastatic lymph nodes in lung cancer patients based on endobronchial ultrasonography features

AIM The aim of this study was to identify easy and relatively effective ultrasound criteria for metastatic mediastinal lymph node prediction. MATERIALS AND METHODS A retrospective chart review of patients who underwent endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) from March 2014 to September 2016 was performed. We used the following EBUS sonographic features for metastatic lymph node prediction: 1) length of the short axis, 2) shape, 3) margin, 4) echogenicity, 5) central hilar structure, and 6) coagulation necrosis sign. These sonographic findings were compared with the final pathology results or clinical follow-up. RESULTS A total of 227 lymph nodes were retrospectively evaluated in 133 lung cancer patients; 72% of the lymph nodes had been proven to be malignant metastasis. Logistic regression analysis revealed that the length of the short axis, shape, margin, and echogenicity were independent predictive factors for metastasis. We developed a sum score based on these four sonographic features. A larger sum score trended toward a greater possibility of malignancy. If all four predictive factors were preserved, the diagnostic accuracy, the value of the specificity and the positive predictive value of the sonographic feature would be higher than 90%. CONCLUSIONS The sonographic features of EBUS are valuable tools in predicting metastatic lymph nodes in lung cancer patients.

Tuberculosis contact investigation in an intermediate burden setting: implications from a large tuberculosis contact cohort in Taiwan

There are still several unanswered research questions regarding tuberculosis (TB) contact investigations [1–4]. For example, up-to-date epidemiological studies regarding TB contacts in the area of intermediate incidence are not readily available [5]. The long-term risk of TB, especially beyond 5 years, remains undetermined [6]. Risk factors for TB development among contacts are also not well defined [2]. To expand current understanding and knowledge of TB contact investigation, we recruited a population-based TB contacts cohort utilising the National Health Insurance Research Database of Taiwan, which included medical care claims data of 99% Taiwan residents [7]. Taiwan TB contact cohort: 0.5% 1-year yield, age ≥65 as significant risk factor and elevated TB risk at 5th year http://ow.ly/9ZGr30dpkMc

Gefitinib or erlotinib in previously treated non-small-cell lung cancer patients: A cohort study in Taiwan

Among treatment modalities for lung cancer, the most promising therapy is the use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs). Both erlotinib and gefitinib, the two first‐generation EGFR‐TKIs, exhibit significant clinical responses for patients with lung adenocarcinoma. However, few studies have compared the effects of these two drugs, and results have been inconclusive because of the small sample sizes in these studies. Therefore, this study was conducted to investigate this issue. This retrospective nationwide cohort study enrolled NSCLC patients who received EGFR‐TKIs after previous chemotherapy in Taiwan between 1996 and 2010 from the National Health Insurance Research Database. Clinical response and survival after receiving erlotinib and gefitinib were compared using logistic and Cox regression analyses, respectively. Inverse propensity score weighting and a sensitivity analysis in the EGFR‐TKI responder (clinical improvement by taking EGFR‐TKIs for 90 days), adherent patients (receiving EGFR‐TKI on a daily basis), adenocarcinoma, and adenocarcinoma with second‐line TKIs subgroup were performed for bias adjustment. A total of 7222 patients, including 4592 (63.6%) who received gefitinib, were identified. In the survival analysis, erlotinib was associated with a decline in 1‐year progression‐free survival (PFS) (hazard ratio, HR: 1.15 [1.09–1.21]) and overall survival (OS) (HR: 1.10 [1.03–1.18]). The effects of various TKIs were consistent in the 4939 EGFR‐TKI responders, adherent subgroup, adenocarcinoma subgroup, and adenocarcinoma with second‐line TKIs subgroup. In previously treated EGFT‐TKI‐naive NSCLC patients, those receiving gefitinib exhibited a longer PFS and OS than those receiving erlotinib. Additional large‐scale randomized controlled trials are warranted to confirm this finding.