[Show abstract][Hide abstract] ABSTRACT: Predicting severity of pancreatitis is an important goal. Clinicians are still searching for novel and simple biomarkers that can better predict persistent organ failure (OF). Lipoproteins, especially high-density lipoprotein (HDL), and apolipoprotein A-I (APO A-I), have been shown to have anti-inflammation effects in various clinical settings. Severe acute pancreatitis (SAP) is associated with hypo-lipoproteinemia. We studied whether the concentrations of HDL and APO A-I can predict persistent OF in patients with predicted SAP admitted to the ICU.
In 66 patients with predicted SAP, we prospectively evaluated the relationship between lipid levels, inflammatory cytokines and clinical outcomes, including persistent OF and hospital mortality. Blood samples were obtained within 24 hours of admission to the ICU.
HDL and APO A-I levels were inversely correlated with various disease severity scores. Patients with persistent OF had lower levels of HDL and APO A-I, while those with transient OF had lower levels of interleukin-6, tumor necrosis factor-α and lower rates of hospital mortality. Meanwhile, hospital non-survivors had lower concentrations of HDL, and APO A-I compared to the survivors. By using the area under the receiver operating characteristic (AUROC) curve, both HDL and APO A-I demonstrated an excellent discriminative power for predicting persistent OF among all patients (AUROC 0.912 and 0.898 respectively) and among those with OF (AUROC 0.904 and 0.895 respectively). Pair-wise comparison of AUROC showed that both HDL and APO A-I had better discriminative power than C-reactive protein to predict persistent OF.
Serum levels of HDL and APO A-I at admission to the ICU are inversely correlated with disease severity in patients with predicted SAP and can predict persistent OF in this clinical setting.
[Show abstract][Hide abstract] ABSTRACT: Background and objective:
The overprescription of inhaled corticosteroids (ICS) in the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A and B patients with chronic obstructive pulmonary disease (COPD) is not uncommon in clinical practice. The aim of this study was to explore the factors associated with the use of ICS in these patients.
The Taiwan obstructive lung disease (TOLD) study was a retrospective, observational nationwide survey of COPD patients conducted at 12 hospitals (n=1,096) in Taiwan. Multivariate logistic regression models were used to explore the predictors of ICS prescription in GOLD group A and B patients.
Among the group A (n=179) and group B (n=398) patients, 198 (34.3%) were prescribed ICS (30.2% in group A and 36.2% in group B, respectively). The wheezing phenotype was present in 28.5% of group A and 34.2% of group B patients. Wheezing was the most significant factor for an ICS prescription in group A (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.14-4.75; P=0.020), group B (OR, 1.93; 95% CI, 1.24-2.99; P=0.004), and overall (OR, 2.04; 95% CI, 1.40-2.96; P<0.001). The COPD assessment test score was also associated with an ICS prescription in group B (OR, 1.04; 95% CI, 1.00-1.07; P=0.038).
About one-third of the GOLD group A and B patients with COPD in Taiwan are prescribed ICS. Our findings suggest that wheezing and COPD assessment test score are related to the prescription of ICS in these patients.
International Journal of COPD 09/2015; 10:1951-1956. DOI:10.2147/COPD.S88114 · 3.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The association between estrogen receptor (ER) gene polymorphism and lung cancer risk is rarely studied. This study aimed to explore the ER gene polymorphisms associated with the lung adenocarcinoma risk in never-smoking women.
This study evaluated 532 never-smoking female patients with lung adenocarcinoma and 532 healthy controls. The ESR1 and ESR2 single nucleotide polymorphism (SNP) data were retrieved from a genome-wide association study. Using a multivariate-adjusted logistic regression assay, the associations of ESR1 and ESR2 SNPs with the lung adenocarcinoma risk were estimated, respectively. Expression quantitative trait loci (eQTL) analysis were performed to investigate the possible functional roles of ER gene SNPs.
For ESR1, 7 tagged SNPs were identified. Among them, rs7753153 and rs985192 were associated with lung adenocarcinoma risk. (rs7753153: OR: 1.509, 95% CI: 1.168-1.950; rs985192: OR: 1.309, 95% CI: 1.001-1.712). For ESR2, only rs3020450 was associated with lung adenocarcinoma risk. (OR: 2.110, 95% CI: 1.007-4.422). Subjects without hormone replacement therapy (HRT) use carrying at-risk genotypes had a significantly higher lung adenocarcinoma risk than subjects with HRT carrying no at-risk genotypes (rs7753153 GG, OR: 2.133, 95% CI: 1.415-3.216; rs985192 AA/AC, OR: 1.752, 95% CI: 1.109-2.768; rs3020450 AG/GG, OR: 7.162, 95% CI: 1.608-31.90). Risk genotypes of rs7753153 (p=0.0248) and rs9479122 (p=0.0251) were associated with decreased ESR1 expression.
ER gene SNPs are associated with lung adenocarcinoma risk in never-smoking women. The joint effects of ER gene SNPs and HRT use on lung adenocarcinoma risk highlight the importance of the gene-environment interaction in lung carcinogenesis.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 08/2015; DOI:10.1097/JTO.0000000000000646 · 5.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lung cancer is the leading cause of cancer-related death worldwide. Even early-stage patients might encounter disease recurrence with relative high risk. Effective postoperative therapy is based on an accurate assessment of treatment failure after surgery. The aim of this study is to construct a disease-free survival (DFS) prediction model and stratify patients into different risk score groups.A total of 356 pathological stage I patients (7th American Joint Committee on Cancer) who underwent lung resection from January 2005 through June 2011 were retrospectively reviewed. Of these patients, 63 patients were eliminated for this study. A total of 293 p-stage I patients were included for further univariate and multivariate analysis. Clinical, surgical, and pathological factors associated with high risk of recurrence were analyzed, including age, gender, smoking status, additional primary malignancy (APM), operation method, histology, visceral pleural invasion, angiolymphatic invasion, tumor necrosis, and tumor size.Of the 293 p-stage I non-small cell lung cancer (NSCLC) patients examined, 143 were female and 150 were male, with a mean age of 62.8-years old (range: 25-83-years old). The 5-year DFS and overall survival rates after surgery were 58.9% and 75.3%, respectively. On multivariate analysis, current smoker (hazards ratio [HR]: 1.63), APM (HR: 1.86), tumor size (HR: 1.54, 2.03), nonanatomic resections (HR: 1.81), adenocarcinoma histology (HR: 2.07), visceral pleural invasion (HR: 1.54), and angiolymphatic invasion (HR: 1.53) were found to be associated with a higher risk of tumor recurrence. The final model showed a fair discrimination ability (C-statistic = 0.68). According to the difference risk group, we found patients with intermediate or higher risk group had a higher distal relapse tendency as compared with low risk group (P = 0.016, odds ratio: 3.31, 95% confidence interval: 1.21-9.03).Greater than 30% of disease recurrences occurred after surgery for stage I NSCLC patients. That is why we try to establish an effective DFS predicting model based on clinical, pathological, and surgical covariates. However, our initial results still need to be validated and refined into greater population for better application in clinical use.
Medicine 08/2015; 94(32):e1337. DOI:10.1097/MD.0000000000001337 · 5.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Diffuse alveolar damage (DAD) is the pathological hallmark of acute respiratory distress syndrome (ARDS), however, the presence of DAD in the clinical criteria of ARDS patients by Berlin definition is little known. This study is designed to investigate the role of DAD in ARDS patients who underwent open lung biopsy.
We retrospectively reviewed all ARDS patients who met the Berlin definition and underwent open lung biopsy from January 1999 to January 2014 in a referred medical center. DAD is characterized by hyaline membrane formation, lung edema, inflammation, hemorrhage and alveolar epithelial cell injury. Clinical data including baseline characteristics, severity of ARDS, clinical and pathological diagnoses, and survival outcomes were analyzed.
A total of 1838 patients with ARDS were identified and open lung biopsies were performed on 101 patients (5.5 %) during the study period. Of these 101 patients, the severity of ARDS on diagnosis was mild of 16.8 %, moderate of 56.5 % and severe of 26.7 %. The hospital mortality rate was not significant difference between the three groups (64.7 % vs 61.4 % vs 55.6 %, p = 0.81). Of the 101 clinical ARDS patients with open lung biopsies, 56.4 % (57/101) patients had DAD according to biopsy results. The proportion of DAD were 76.5 % (13/17) in mild, 56.1 % (32/57) in moderate and 44.4 % (12/27) in severe ARDS and there is no significant difference between the three groups (p = 0.113). Pathological findings of DAD patients had a higher hospital mortality rate than non-DAD patients (71.9 % vs 45.5 %, p = 0.007). Pathological findings of DAD (odds ratio: 3.554, 95 % CI, 1.385-9.12; p = 0.008) and Sequential Organ Failure Assessment score on the biopsy day (odds ratio: 1.424, 95 % CI, 1.187-1.707; p<0.001) were significantly and independently associated with hospital mortality. The baseline demographics and clinical characteristics were not significantly different between DAD and non-DAD patients.
The correlation of pathological findings of DAD and ARDS diagnosed by Berlin definition is modest. A pathological finding of DAD in ARDS patients is associated with hospital mortality and there are no clinical characteristics that could identify DAD patients before open lung biopsy.
[Show abstract][Hide abstract] ABSTRACT: Liver cirrhosis is a major risk factor for hepatocellular carcinoma (HCC), and all liver study societies recommend HCC surveillance in patients with cirrhosis. However, no ideal modality for HCC surveillance has been determined. The aim of this study is to assess the effectiveness of α-fetoprotein (AFP) measurement in HCC surveillance.
In this retrospective analysis, all patients with cirrhosis, who received HCC surveillance through ultrasound (US) and AFP measurement between January 2002 and July 2010, were followed up until June 2013. The performance effectiveness of surveillance using AFP, US, or both in HCC detection was compared.
Overall, 1,597 patients were followed for a median duration of 4.75 (range 1.42-12) years. Over the 8563.25-person-year follow-up period, 363 patients (22.7%) developed HCCs. For HCC detection, the area under the receiver operator characteristic curve of surveillance AFP was 0.844 (95% confidence interval: 0.820-0.868, P<0.001). When the traditional cutoff value of 20 ng/ml was used, the sensitivity and specificity of AFP were 52.9% and 93.3%, respectively. US exhibited a sensitivity and specificity of 92.0% and 74.2%, respectively. A combination of US and AFP exhibited a sensitivity and specificity of 99.2% and 68.3%, respectively. By using cut-off at 20 ng/ml and AFP level increase ≥2 × from its nadir during the previous 1 year, the combination of US and AFP yielded a sensitivity of 99.2% and an improved specificity of 71.5%.
The complementary use of AFP and US improved the effectiveness of HCC surveillance in patients with cirrhosis.Am J Gastroenterol advance online publication, 14 April 2015; doi:10.1038/ajg.2015.100.
The American Journal of Gastroenterology 04/2015; 110(6). DOI:10.1038/ajg.2015.100 · 10.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Viral and bacterial infections are the most common causes of chronic obstructive pulmonary disease (COPD) exacerbations. Whether serum inflammatory markers can differentiate bacterial from virus infection in patients with COPD exacerbation requiring emergency department (ED) visits remains controversial.
Viral culture and polymerase chain reaction (PCR) were used to identify the viruses in the oropharynx of patients with COPD exacerbations. The bacteria were identified by the semiquantitative culture of the expectorated sputum. The peripheral blood white blood cell (WBC) counts, serum C-reactive protein (CRP), procalcitonin (PCT), and clinical symptoms were compared among patients with different types of infections.
Viruses were isolated from 16 (22.2%) of the 72 patients enrolled. The most commonly identified viruses were parainfluenza type 3, influenza A, and rhinovirus. A total of 30 (41.7%) patients had positive bacterial cultures, with the most commonly found bacteria being Haemophilus influenzae and Haemophilus parainfluenzae. Five patients (6.9%) had both positive sputum cultures and virus identification. The WBC, CRP, and PCT levels of the bacteria-positive and bacteria-negative groups were not statistically different. Multivariate analysis showed that patients with increased sputum volumes during the COPD exacerbations had higher risks of recurrent exacerbations in the 1-year period following the first exacerbation.
WBC, CRP, or PCT could not differentiate between bacterial and viral infections in patients with COPD exacerbation requiring ED visits. Those with increased sputum during a COPD exacerbation had higher risks for recurrent exacerbations.
International Journal of COPD 04/2015; 10:767. DOI:10.2147/COPD.S76740 · 3.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We previously carried out a multi-stage genome-wide association study (GWAS) on lung cancer among never smokers in the Female Lung Cancer Consortium in Asia (FLCCA) (6,609 cases, 7,457 controls) that identified novel susceptibility loci at 10q25.2, 6q22.2, and 6p21.32, and confirmed two previously identified loci at 5p15.33 and 3q28. Household air pollution (HAP) attributed to solid fuel burning for heating and cooking, is the leading cause of the overall disease burden in Southeast Asia, and is known to contain lung carcinogens. To evaluate the gene-HAP interactions associated with lung cancer in loci independent of smoking, we analyzed data from studies participating in FLCCA with fuel use information available (n = 3; 1,731 cases; 1,349 controls). Coal use was associated with a 30 % increased risk of lung cancer (OR 1.3, 95 % CI 1.0-1.6). Among the five a priori SNPs identified by our GWAS, two showed a significant interaction with coal use (HLA Class II rs2395185, p = 0.02; TP63 rs4488809 (rs4600802), p = 0.04). The risk of lung cancer associated with coal exposure varied with the respective alleles for these two SNPs. Our observations provide evidence that genetic variation in HLA Class II and TP63 may modify the association between HAP and lung cancer risk. The roles played in the cell cycle and inflammation pathways by the proteins encoded by these two genes provide biological plausibility for these interactions; however, additional replication studies are needed in other non-smoking populations.
Human Genetics 01/2015; 134(3). DOI:10.1007/s00439-014-1528-z · 4.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tuberculosis is one of the major infectious diseases in Taiwan. It has an especially high prevalence in diabetes patients, in whom it is usually asymptomatic and are more likely to result in drug-resistant tuberculosis. The aim of the study was to aggressively screen high risk diabetic elderly, identify the prevalence of tuberculosis and its determinants.
Type 2 diabetes patients aged over 65 years were enrolled. They received chest X-rays, blood tests and the questionnaires to assess their medical history and symptoms. Suspicious cases were referred to the pulmonary or infectious disease outpatient clinics. Pulmonary tuberculosis was confirmed by sputum culture. Variables between groups were analyzed by Student t test, Chi-square test or Fisher's exact test. Risk factors were assessed using univariate logistic regression and multiple logistic regression.
A total of 3,087 patients participated this screening program and 7 patients screened positive for pulmonary tuberculosis. Another 5 patients were being under treatment when participating screening program. The prevalence rate was 3.89 per thousand people. The patients with male gender, smoking, liver cirrhosis or subjective body weight loss were associated with an increased risk of tuberculosis significantly. Subjective body weight loss (OR: 6.635 [95% CI: 2.096-21.007]), liver cirrhosis (OR: 10.307 [95% CI: 2.108-50.395]) and history smoking (OR: 3.981 [95% CI: 1.246-12.718]) are independent risk factors. Among all 73 patients with active tuberculosis or tuberculosis history, they tended to be male, lower body mass index (BMI), more smoking history, more alcohol consumption, more family history of tuberculosis, higher low density lipoprotein (LDL), and less hypertension. However, there was no significant difference in the glycated hemoglobin (HbA1c) levels between the tuberculosis group and non-tuberculosis group.
Active screening program is helpful in detecting pulmonary tuberculosis in elderly diabetes patients. Subjective body weight loss, smoking and liver cirrhosis are independent risk factors.
BMC Public Health 01/2015; 15(1):3. DOI:10.1186/1471-2458-15-3 · 2.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
N2-positive non-small cell lung cancer (NSCLC) exhibits extremely low survival rates. The role of surgery in operable locally advanced N2 NSCLC remains controversial. In this study, we tried to analyze the role of surgery in resectable N2 NSCLC and the relationship between survival and clinico-pathologic factors from a pathologic point of view.
108 resectable pathologic N2-positive NSCLC patients, diagnosed from January 2005 to July 2012, were enrolled in this study. We retrospectively reviewed the medical records, image studies, and pathology reports to collect the clinico-pathologic factors in these patients.
Those who received lobectomy (p = 0.002) and had a metastatic lymph node ratio less than 0.4 (p = 0.01) had a better overall survival rate. In addition, our study also showed that perineural invasion may play a significant role in disease-free survival (p = 0.01) CONCLUSIONS: Metastatic lymph node ratio greater than 0.4 and non-anatomic resection were poor prognostic factors for disease-free survival. Anatomic resection for selected N2 patients may play a crucial role in the overall survival rate. Perineural invasion showed an adverse impact on disease-free survival, but further investigation is warranted.
[Show abstract][Hide abstract] ABSTRACT: Background/purpose
Noninvasive positive pressure ventilation has been regarded as a strategy for improving exercise performance. Whether an increase in the ventilatory support level improves exercise performance in patients who have received invasive ventilation is unknown. The purpose of this study is to examine the effects of an additional level of pressure support (PS) ventilation on exercise tolerance in patients undergoing prolonged mechanical ventilation (PMV).
This study examined 15 patients who were undergoing PMV. All patients performed an upper-arm exercise test at three PS levels: the baseline PS level (PS), a level 2 cmH2O higher than the baseline level (PS+2), and a level 4 cmH2O higher than the baseline level (PS+4). The physiological response, reasons for discontinuing the exercise test, and exercise duration were recorded and analyzed.
The tidal volume increased significantly from 271.7 ± 54.7 mL to 398.3 ± 88.7 mL at the PS+4 level (p = 0.01). Significant differences in exercise duration were observed at different PS levels. The exercise duration was significantly longer at the PS+4 level than at the PS and PS+2 levels (146.3 ± 139.9 seconds vs. 108.5 ± 85.9 seconds vs. 72.8 ± 43.9 seconds, p = 0.038) as their corresponding order. There were significant relationships between resting respiratory rate and exercise duration at the PS (r = −0.639, p = 0.034) and PS+2 levels (r = −0.668, p = 0.025).
In patients undergoing PMV, an additional PS level of up to 4 cmH2O compared with the baseline setting may help to improve exercise tolerance by prolonging exercise duration.
Journal of the Formosan Medical Association 10/2014; DOI:10.1016/j.jfma.2014.09.002 · 1.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Calreticulin (CALR) mutations were recently identified in patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF) devoid of JAK2 and MPL mutations. We evaluated the clinical, laboratory, and molecular features of a Taiwanese population of patients with ET. Among 147 ET patients, CALR mutations were detected in 33 (22.5 %), JAK2V617F in 94 (63.9 %), and MPL mutations in 4 (2.7 %). Sixteen (10.9 %) patients were negative for all three mutations (CALR, JAK2V617F, and MPL; triple negative). Interestingly, one patient with the type 2 CALR mutation also harbored a low allele burden (0.025 %) of JAK2V617F mutation. Furthermore, we found a novel CALR mutation, with the resultant protein sharing an identical amino acid sequence to the type 6 CALR mutant. Compared to those with JAK2 mutation, CALR-mutated ET patients were characterized by younger age, lower leukocyte count, higher platelet count, and decreased risk of thrombosis. CARL mutations had a favorable impact on thrombosis-free survival (TFS) for ET patients, whereas the respective TFS outcomes were similarly poorer in JAK2-mutated ET and PV patients. Multivariate analysis confirmed that younger age (<60 years), presence of CALR mutations, and a lower platelet count (<1,000 × 10(9)/L) were independently associated with a longer TFS in ET patients. The current study demonstrates that CALR mutations characterize a special group of ET patients with unique phenotypes that are not discrepant from those seen in Western countries.
Annals of Hematology 07/2014; 93(12). DOI:10.1007/s00277-014-2151-8 · 2.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mechanical ventilation used in patients with acute lung injury can damage pulmonary epithelial cells through production of inflammatory cytokines, oxygen radicals, and neutrophil infiltration, termed ventilator-induced lung injury. Neutrophil elastase, nuclear factor-κB (NF-κB), and NF-κB repressing factor (NRF) have previously been shown to participate in the regulation of macrophage inflammatory protein-2 (MIP-2) during airway inflammation. However, the mechanisms regulating interactions among mechanical ventilation, neutrophil influx, and NF-κB/NRF remain unclear. Thus, we hypothesized that neutrophil elastase inhibitor attenuated ventilation-induced neutrophil recruitment and MIP-2 production through inhibition of the NF-κB/NRF pathway. Male C57BL/6 mice were exposed to low-tidal-volume (6 mL/kg) or high-tidal-volume (30 mL/kg) mechanical ventilation using room air with or without 2 µg/g NF-κB inhibitor SN50 or 6 µg/g NRF short interfering RNA or 100 µg/g neutrophil elastase inhibitor administration. Nonventilated mice served as a control group. Evan blue dye, lung wet-to-dry weight ratio, free radicals, myeloperoxidase, histopathologic grading of lung tissue, inflammatory cytokines, Western blot of NF-κB and NRF, and gene expression of NRF were measured to establish the extent of lung injury. Neutrophil elastase inhibitor ameliorated high-tidal-volume ventilation-induced lung injury, neutrophil influx, production of MIP-2 and malondialdehyde, activation of NF-κB and NRF, apoptotic epithelial cell death, and disruption of bronchial microstructure in mice. Mechanical stretch-augmented acute lung injury was also attenuated through pharmacological inhibition of NF-κB activity by SN50 and NRF expression by NRF short interfering RNA. Our data suggest that neutrophil elastase inhibitor attenuates high-tidal-volume mechanical ventilation-induced neutrophil influx, oxidative stress, and production of MIP-2, at least partly, through inhibition of NF-κB/NRF pathway. Understanding the protective effects of neutrophil elastase inhibitor associated with the reduction of MIP-2 allow clarification of the pathophysiological mechanisms regulating severe lung inflammation and development of possible therapeutic strategies involved in acute lung injury.
Experimental Biology and Medicine 04/2014; 239(8). DOI:10.1177/1535370214529393 · 2.17 Impact Factor