Shih-Feng Liu

Toll-like receptor 2 gene polymorphisms, pulmonary tuberculosis, and natural killer cell counts

BackgroundTo investigate whether the toll-like receptor 2 polymorphisms could influence susceptibility to pulmonary TB, its phenotypes, and blood lymphocyte subsets.MethodsA total of 368 subjects, including 184 patients with pulmonary TB and 184 healthy controls, were examined for TLR2 polymorphisms over locus -100 (microsatellite guanine-thymine repeats), -16934 (T>A), -15607 (A>G), -196 to -174 (insertion>deletion), and 1350 (T>C). Eighty-six TB patients were examined to determine the peripheral blood lymphocyte subpopulations.ResultsWe newly identified an association between the haplotype [A-G-(insertion)-T] and susceptibility to pulmonary TB (p = 0.006, false discovery rate q = 0.072). TB patients with systemic symptoms had a lower -196 to -174 deletion/deletion genotype frequency than those without systemic symptoms (5.7% vs. 17.7%; p = 0.01). TB patients with the deletion/deletion genotype had higher blood NK cell counts than those carrying the insertion allele (526 vs. 243.5 cells/μl, p = 0.009). TB patients with pleuritis had a higher 1350 CC genotype frequency than those without pleuritis (12.5% vs. 2.1%; p = 0.004). TB patients with the 1350 CC genotype had higher blood NK cell counts than those carrying the T allele (641 vs. 250 cells/μl, p = 0.004). TB patients carrying homozygous short alleles for GT repeats had higher blood NK cell counts than those carrying one or no short allele (641 vs. 250 cells/μl, p = 0.004).ConclusionsTLR2 genetic polymorphisms influence susceptibility to pulmonary TB. TLR2 variants play a role in the development of TB phenotypes, probably by controlling the expansion of NK cells.

Differences in clinical and laboratory characteristics and disease severity between children and adults with dengue virus infection in Taiwan, 2002.

To compare the clinical and laboratory characteristics and disease severity between adults and children with dengue in Taiwan in 2002, we retrospectively studied 661 serologically confirmed dengue-infected patients (606 adults and 55 children) admitted between June and December 2002 to a single medical centre. The medical charts of the patients were reviewed for demographic, clinical, laboratory and imaging information. Compared with children, adult patients were found to have: higher incidences of arthralgia (P<0.001), myalgia (P=0.002), headache (P=0.028), abdominal pain (P=0.004) and upper gastrointestinal bleeding (P=0.013); lower platelet counts (P<0.001), prothrombin time (P=0.030) and serum albumin levels (P=0.037); a higher incidence of elevated alanine aminotransferase levels (P=0.001); and a higher prevalence of dengue haemorrhagic fever (DHF) (14.4% vs. 3.6%; P=0.026). The current data showed differences in clinical manifestations and laboratory characteristics between children and adults with dengue virus infection. Notably, a higher incidence of DHF was observed in adult patients compared with children in the 2002 dengue epidemic in Taiwan.

Levels of Circulating Microparticles in Lung Cancer Patients and Possible Prognostic Value

Background. Endothelial-derived microparticles (EDMPs) and platelet-derived microparticles (PDMPs) have been reported to be increasing in various diseases including malignant diseases. Here, we investigated whether these MPs may be useful biomarkers for predicting lung cancer (LC) disease status, cell type, or metastasis. Methods and Results. One hundred and thirty LC patients were prospectively enrolled into the study between April 2011 and February 2012. Flow cytometric analysis demonstrated that the circulating levels of platelet-derived activated MPs (PDAc-MPs), platelet-derived apoptotic MPs (PDAp-MPs), endothelial-derived activated MPs (EDAc-MPs), and endothelial-derived apoptotic MPs (EDAp-MPs) were significantly higher in LC patients than in 30 age- and gender-matched normal control subjects (all P < 0.05). Additionally, circulating level of PDAc-MPs was significantly lower (P = 0.031), whereas the circulating levels of the other three biomarkers did not differ (all P > 0.1) in early stage versus late stage LC patients. Furthermore, the circulating levels of the four types of MPs did not differ among patients with different disease statuses (i.e., disease controlled, disease progression, and disease without treatment, i.e., fresh case) (all P > 0.2) or between patients with or without LC metastasis (all P > 0.5). Moreover, only the circulating level of EDAp-MPs was significantly associated with the different cell types (i.e., squamous cell carcinoma, adenocarcinoma, and small cell carcinoma) of LC (P = 0.045). Conclusion. Circulating MP levels are significantly increased in LC patients as compared with normal subjects. Among the MPs, only an increased level of EDAp-MPs was significantly associated with different LC cell types.

Prognostic factors of tracheobronchial mucoepidermoid carcinoma--15 years experience.

Background and objectives:  Mucoepidermoid carcinoma of the tracheobronchial tree is a rare tumour which displays a variable degree of clinical aggressiveness and malignancy. The relationship between the patients prognosis and the tumours histological features and clinical behaviour is uncertain. The aim of this study was to identify the clinicopathological features and analyse the outcomes of patients with this type of cancer.

Impact of clinical severity index, infective pathogens, and initial empiric antibiotic use on hospital mortality in patients with ventilator-associated pneumonia

BACKGROUND The prompt initial use of appropriate antibiotics should improve mortality rates in adults with ventilator-associated pneumonia (VAP). However, the incidence of multidrug-resistant (MDR) pathogen infections is on the rise, and the choice of the initial empiric antibiotic may be challenging. We investigated whether appropriate initial antibiotic therapy, infective pathogens, and the clinical severity index influence hospital mortality in patients with VAP and determined independent risk factors for the same. METHODS This study evaluated 163 adult patients (aged ≥ 18 years) at Chang Gung Memorial Hospital, Kaohsiung, Taiwan, from January 1, 2007, to January 31, 2008. Eligibility was evaluated based on criteria for VAP. Sequential Organ Failure Assessment (SOFA) scores, Acute Physiological Assessment and Chronic Health Evaluation II (APACHE II) scores, oxygenation index, underlying comorbidities, septic shock status, previous tracheostomy status, and factors related to pneumonia were collected for analysis. RESULTS Ninety-two patients survived from a total 163 patients with VAP during the course of their confinement in the intensive care unit. Multivariable logistic regression analysis identified that a pre-existing Charlson Comorbidity Index score (P = .011), initial oxygenation index (P = .025), SOFA score (P = .043), VAP caused by Acinetobacter baumanii (P = .030), and infection with MDR pathogens (P = .003) were independent risk factors for hospital mortality in patients with VAP. CONCLUSION High Charlson Comorbidity Index score, high initial oxygenation index, high SOFA score, and infection with Acinetobacter baumannii or MDR pathogens significantly affect hospital mortality in patients with VAP.

Prognostic values of serum IP-10 and IL-17 in Patients with Pulmonary Tuberculosis

Objective: To identify patients at high risk of relapse after anti-tuberculosis (TB) therapy or with poor long-term outcomes. Methods: Fifty-one patients with pulmonary TB: 7 were classified as high association with both cavitations on initial chest radiography and positive sputum smear/cultures after two months of anti-TB treatment (HA group); 19 medium association (MA, one risk alone); and 25 low association (LA, neither risk). Serum interferon (IFN)-γ-inducible protein 10 (IP-10), interleukin-17 (IL-17), and C-reactive protein levels were investigated. Results: There was a trend towards higher serum IP-10 levels (p = 0.042) for HA patients throughout the 6-month treatment period. Month-2 IP-10 levels were higher in the HA than in the MA/LA group (656.2 ± 234.4 vs. 307.6 ± 258.5 pg/ml, adjusted p = 0.005). Receiver operating characteristic curves showed that the risk of relapse was well-captured by month-2 IP-10 levels at a cut-off value of 431 pg/ml (AUC=0.857, 95% CI 0.75–0.97, p = 0.003). Month-2 serum IL-17 levels were lower in non-survivors than survivors (15.7 ± 2.9 pg/ml vs. 24.6 ± 8.2 pg/ml, p = 0.001). Multivariate analysis demonstrated that a month-2 serum IL-17 level of ≤ 17 pg/ml (p = 0.026) was independently associated with all-cause mortality. Conclusions: Serum IP-10 and IL-17 levels after 2 months of anti-TB treatment may be biomarkers for estimating risk of both cavitation and delayed sputum conversion, and for predicting long-term mortality, respectively.

Leukocyte Mitochondrial DNA Copy Number Is Associated with Chronic Obstructive Pulmonary Disease.

Background Oxidative stress is known to be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Evidence suggests that leukocytes mitochondria DNA (mtDNA) is susceptible to undergo mutations, insertions, or depletion in response to reactive oxidative stress (ROS). We hypothesize that mtDNA copy number is associated with the development of COPD. Methodology/Principal Findings Relative mtDNA copy number was measured by a quantitative real-time PCR assay using DNA extracted from peripheral leukocytes. MtDNA copy number of peripheral leukocytes in the COPD group (n = 86) is significantly decreased compared with non-smoker group (n = 77) (250.3± 21.5 VS. 464.2± 49.9, P<0.001). MtDNA copy number in the COPD group was less than that in the healthy smoking group, but P value nearly achieved significance (250.3± 21.5 VS. 404.0± 76.7, P = 0.08) MtDNA copy number has no significance with age, gender, body mass index, current smoking, and pack-years in COPD group, healthy smoker group and no smoker group, respectively. Serum glutathione level in the COPD group is significantly decreased compared with healthy smoker and non-smoker groups (4.5± 1.3 VS. 6.2± 1.9 and 4.5± 1.3 VS. 7.1±1.1 mU/mL; P<0.001 respectively). Pearson correlation test shows a significant liner correlation between mtDNA copy number and serum glutathione level (R = 0.2, P = 0.009). Conclusions/Significance COPD is associated with decreased leukocyte mtDNA copy number and serum glutathione. COPD is a regulatory disorder of leukocytes mitochondria. However, further studies are needed to determine the real mechanisms about the gene and the function of mitochondria.

Colistin inhalation monotherapy for ventilator-associated pneumonia of Acinetobacter baumannii in prematurity

Ventilator‐associated pneumonia (VAP) caused by Acinetobacter baumannii is increasing. It has a high mortality rate but experience in using inhaled colistin as monotherapy for VAP in children, especially pre‐term infants, is limited. This study presents experiences using aerosolized colistin as monotherapy for VAP due to A. baumannii infection in pre‐term infants.

Factors influencing short-term re-admission and one-year mortality in patients with chronic obstructive pulmonary disease.

Background and objectives:  Fourteen day re‐admission rates are deemed to be an important indicator of the quality of medical care for COPD in Taiwan. This study identified the characteristics of patients with COPD who required short‐term re‐admission and analysed the risk factors for 1‐year mortality.

Monitoring Treatment Responses in Patients with Pulmonary TB Using Serial Lung Gallium-67 Scintigraphy

OBJECTIVE Gallium-67 scintigraphy is more sensitive than chest radiography in a single concurrent detection of pulmonary tuberculosis (TB). As for inflammation, the intensity of pulmonary uptake of 67Ga citrate theoretically is a function of the inflammation level in the lung. To maximize clinical applicability of 67Ga scintigraphy in the evaluation of pulmonary TB, we prospectively assessed serial qualitative associations between intensity of the uptake of 67Ga citrate and the severity of lung inflammation, reflected by the burden of Mycobacterium tuberculosis in the sputum of patients undergoing anti-TB chemotherapy. SUBJECTS AND METHODS Each enrolled patient had chest radiographic, microbiologic, 67Ga imaging, and semiquantitation of sputum acid-fast bacillus (AFB) assessments before and at the third and sixth months after receiving anti-TB chemotherapy. The burden of pulmonary M. tuberculosis (presumably, in proportion to the semiquantitation of AFB in sputum) and the intensity of 67Ga citrate uptake in the lung at each synchronized assessment were regarded as a paired variable. Odds ratios were obtained from odds (derived using generalized estimating equations) in favor of higher pulmonary 67Ga uptake in differing scores of semiquantitation of sputum AFB. Linear trend for pulmonary 67Ga citrate uptake corresponding to varied pulmonary M. tuberculosis burdens was assessed using contrast analysis of their odds ratios. RESULTS Thirty patients (24 men and six women) with pulmonary TB were enrolled. Eighty-six paired semiquantitations of sputum AFB-67Ga-scintigraphic studies were collected. Twenty-six patients were cured of their pulmonary TB. The pulmonary 67Ga uptake increased in proportion to the higher score of semiquantitation of sputum AFB (p = 0.009, for trend). CONCLUSION In patients with pulmonary TB, the higher the burden of M. tuberculosis in the lung, the higher the intensity of pulmonary 67Ga citrate uptake. Serial 67Ga-scintigraphy examinations are helpful in evaluations of the effectiveness of anti-TB therapy when assessments based on chest radiography are difficult.