[Show abstract][Hide abstract] ABSTRACT: Carcinogens in cigarette smoke can induce the formation of DNA-DNA cross-links, which are repaired by the Fanconi anemia (FA) pathway, and it is tempting to speculate that this pathway is involved in lung tumorigenesis. This study is to determine whether genetic polymorphism of the FA genes is associated with an elevated risk of lung adenocarcinoma, and whether the association between genotypes and risk is modified by exposure to cigarette smoke.
This case–control study genotyped 53 single-nucleotide polymorphisms (SNPs) in FA genes in 709 patients (354 males and 355 females) with lung adenocarcinoma and in 726 cancer-free individuals (339 males and 387 females). Genotypic frequencies of SNPs were compared between cases and controls to identify important FA genes associated with cancer susceptibility. Joint effects in determining cancer risk contributed by genes and smoking-related risk factors and by multiple genes involved in different FA subpathways were evaluated by multivariate regression analysis and stratified analysis. All analyses were performed on males and females separately, and the comparison of results was considered a way of examining the validity of study findings.
Lung adenocarcinomas in both male and female patients were associated with (a) genotypic polymorphisms of FANCC and FANCD1; (b) a combined effect of harboring a higher number of high-risk genotypes and smoking/passive smoking; (c) specific interactions of multiple genes, proteins encoded by which have been known to work jointly within the FA pathway.
Genetic polymorphism of the FA genes is associated with inter-individual susceptibility to lung adenocarcinoma.
Preview · Article · Dec 2016 · Journal of Biomedical Science
[Show abstract][Hide abstract] ABSTRACT: Malnutrition in patients with chronic obstructive pulmonary disease (COPD) is associated with cachexia, sarcopenia, and weight loss, and may result in poorer pulmonary function, decreased exercise capacity, and increased risk of exacerbations. Providing nutritional supplementation is an important therapeutic intervention, particularly for severely ill COPD patients with malnutrition. Higher calorie intake through nutritional supplementation significantly increases body weight and muscle strength, and improves quality of life in malnourished COPD patients. Difficulties may be experienced by these COPD patients, who are struggling to breathe and eliminate CO2 from the lungs, resulting in dyspnea, hypercapnia, hypoxia, and respiratory acidosis, which exacerbates muscle loss through oxidative stress and inflammatory responses. To overcome these problems, nutritional supplements should aim to reduce metabolic CO2 production, lower respiratory quotient, and improve lung function. Several studies have shown that high-fat supplements produce less CO2 and have lower respiratory quotient value than high-carbohydrate supplements. In addition, high-fat supplements may be the most efficient means of providing a low-volume, calorie-dense supplement to COPD patients, and may be most beneficial to patients with prolonged mechanical ventilation where hypercapnia and malnutrition are most pronounced. Further studies are required to investigate the optimal nutritional supplements for COPD patients according to their disease severity.
Preview · Article · Jan 2016 · Journal of the Formosan Medical Association
[Show abstract][Hide abstract] ABSTRACT: Genome-wide association studies (GWAS) of lung cancer in Asian never-smoking women have previously identified six susceptibility
loci associated with lung cancer risk. To further discover new susceptibility loci, we imputed data from four GWAS of Asian
non-smoking female lung cancer (6877 cases and 6277 controls) using the 1000 Genomes Project (Phase 1 Release 3) data as the
reference and genotyped additional samples (5878 cases and 7046 controls) for possible replication. In our meta-analysis,
three new loci achieved genome-wide significance, marked by single nucleotide polymorphism (SNP) rs7741164 at 6p21.1 (per-allele
odds ratio (OR) = 1.17; P = 5.8 × 10−13), rs72658409 at 9p21.3 (per-allele OR = 0.77; P = 1.41 × 10−10) and rs11610143 at 12q13.13 (per-allele OR = 0.89; P = 4.96 × 10−9). These findings identified new genetic susceptibility alleles for lung cancer in never-smoking women in Asia and merit follow-up
to understand their biological underpinnings.
Full-text · Article · Jan 2016 · Human Molecular Genetics
[Show abstract][Hide abstract] ABSTRACT: Background/purpose:
Diffuse panbronchiolitis (DPB) is a rare clinicopathological entity. To date, no cohort study of DPB has been conducted in Taiwan. Erythromycin treatment improves the clinical outcome of DPB; however, whether relapse will occur or not is unclear. Herein, we report the first retrospective cohort of DPB patients in one medical center in Taiwan, including their clinical presentation and outcomes of erythromycin treatment.
The study comprised a retrospective cohort analysis of 27 patients with a confirmed diagnosis of DPB. Clinical, radiological, and laboratory parameters were analyzed, and the course and outcome of erythromycin treatment were examined.
The mean age at symptom onset was 56.6 ± 18.5 years, and the time between symptom onset and a correct diagnosis was 4.3 ± 4.2 years. The percentages of patients with centrilobular micronodules on chest computed tomography, obstructive ventilator impairment with hypoxemia, and an elevated cold agglutinin titer were 72%, 37%, and 78%, respectively. After erythromycin treatment, 22 of the 27 (81.5%) patients showed clinical improvement, of whom six suffered a relapse. Four of these six patients clinically improved after a second course of erythromycin treatment.
Erythromycin therapy was suitable for DPB in our experience. In this study cohort, 27% experienced a relapse, of which two-thirds of the patients improved after a second course of erythromycin treatment.
Preview · Article · Dec 2015 · Journal of the Formosan Medical Association
[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.
Full-text · Article · Dec 2015 · Critical care (London, England)
[Show abstract][Hide abstract] ABSTRACT: Introduction
Acute respiratory distress syndrome (ARDS) is a syndrome characterized by diffuse pulmonary edema and severe hypoxemia that usually occurs after an injury such as sepsis, aspiration and pneumonia. Little is known about the relation between the setting where the syndrome developed and outcomes in ARDS patients.
This is a 1-year prospective observational study conducted at a tertiary referred hospital. ARDS was defined by the Berlin criteria. Community-acquired ARDS, hospital-acquired ARDS and intensive care unit (ICU)-acquired ARDS were defined as ARDS occurring within 48 hours of hospital or ICU admission, more than 48 hours after hospital admission and ICU admission. The primary and secondary outcomes were short- and long- term mortality rates and ventilator-free and ICU-free days.
Of the 3002 patients screened, 296 patients had a diagnosis of ARDS, including 70 (23.7 %) with community-acquired ARDS, 83 (28 %) with hospital-acquired ARDS, and 143 (48.3 %) with ICU-acquired ARDS. The overall ICU mortality rate was not significantly different in mild, moderate and severe ARDS (50 %, 50 % and 56 %, p = 0.25). The baseline characteristics were similar other than lower rate of liver disease and metastatic malignancy in community-acquired ARDS than in hospital-acquired and ICU-acquired ARDS. A multiple logistic regression analysis indicated that age, sequential organ function assessment score and community-acquired ARDS were independently associated with hospital mortality. For community-acquired, hospital-acquired and ICU-acquired ARDS, ICU mortality rates were 37 % 61 % and 52 %; hospital mortality rates were 49 %, 74 % and 68 %. The ICU and hospital mortality rates of community-acquired ARDS were significantly lower than hospital-acquired and ICU-acquired ARDS (p = 0.001 and p = 0.001). The number of ventilator-free days was significantly lower in ICU-acquired ARDS than in community-acquired and hospital-acquired ARDS (11 ± 9, 16 ± 9, and 14 ± 10 days, p = 0.001). The number of ICU-free days was significantly higher in community-acquired ARDS than in hospital-acquired and ICU-acquired ARDS (8 ± 10, 4 ± 8, and 3 ± 6 days, p = 0.001).
Community-acquired ARDS have lower short- and long-term mortality rates than hospital-acquired or ICU-acquired ARDS.
[Show abstract][Hide abstract] ABSTRACT: The current TNM staging system did not provide disease relapse information. The aim of study was try to establish a predictive survival model for disease and overall survival in nonsmall cell lung cancer patients who presented as resectable disease and to develop a reference for follow-up imaging tool selection. From January 2005 to December 2011, 442 patients who initially presented as resectable disease (stages I–IIIa) and received anatomic resection and mediastinal lymph node dissection were included in the study. Medical charts were thoroughly reviewed and clinico-pathologic factors were collected and analyzed. Visceral pleural invasion, tumor size >5 cm, and postoperative adjuvant therapy were identified as risk factors for poorer disease-free survival. The 5-year disease-free survival from score 0 to 3 was 68.7%, 46.6%, 31.9%, and 26.1%, respectively. The disease relapse percentage for scores 0 to 3 were 26.49%, 50.61%, 65.05%, and 73.81%, respectively. For analysis of overall survival, age >60 years, tumor size >3 cm, and total metastatic lymph node ratio >0.05 were correlated to worse overall survival. Because greater age may be correlated with poor general condition, we re-scored risk factors that correlated to disease severity that ranging from 0 to 2. The 5-year overall survival range from score 0 to 2 was 56.3%, 43.1%, and 13.1%, respectively. Poor prognostic factors correlated to disease-free survival were tumor size >5 cm, visceral pleural invasion, and patients needing to receive postoperative adjuvant therapy. Disease-free survival of resectable nonsmall cell lung cancer patients and disease relapse can be stratified by these 3 factors. Chest tomography may be recommended for patients with 1 or more poor disease-free survival risk factors.
[Show abstract][Hide abstract] ABSTRACT: The American Journal of Gastroenterology is published by Nature Publishing Group (NPG) on behalf of the American College of Gastroenterology (ACG). Ranked the #1 clinical journal covering gastroenterology and hepatology*, The American Journal of Gastroenterology (AJG) provides practical and professional support for clinicians dealing with the gastroenterological disorders seen most often in patients. Published with practicing clinicians in mind, the journal aims to be easily accessible, organizing its content by topic, both online and in print. www.amjgastro.com, *2007 Journal Citation Report (Thomson Reuters, 2008)
Full-text · Article · Nov 2015 · The American Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: AimThe purpose of the study was to develop and psychometrically test the Nurses Clinical Reasoning Scale.Background
Clinical reasoning is an essential skill for providing safe and quality patient care. Identifying pre-graduates’ and nurses’ needs and designing training courses to improve their clinical reasoning competence becomes a critical task. However, there is no instrument focusing on clinical reasoning in the nursing profession.DesignCross-sectional design was used. This study included the development of the scale, a pilot study that preliminary tested the readability and reliability of the developed scale and a main study that implemented and tested the psychometric properties of the developed scale.Method
The Nurses Clinical Reasoning Scale was developed based on the Clinical Reasoning Model. The scale includes 15 items using a Likert five-point scale. Data were collected from 2013–2014. Two hundred and fifty-one participants comprising clinical nurses and nursing pre-graduates completed and returned the questionnaires in the main study. The instrument was tested for internal consistency and test–retest reliability. Its validity was tested with content, construct and known-groups validity.ResultsOne factor emerged from the factor analysis. The known-groups validity was confirmed. The Cronbach's alpha for the entire instrument was 0·9.Conclusion
The reliability and validity of the Nurses Clinical Reasoning Scale were supported. The scale is a useful tool and can be easily administered for the self-assessment of clinical reasoning competence of clinical nurses and future baccalaureate nursing graduates. Study limitations and further recommendations are discussed.
No preview · Article · Oct 2015 · Journal of Advanced Nursing
[Show abstract][Hide abstract] ABSTRACT: According to the National Comprehensive Cancer Network (NCCN) guidelines, treatment plans for nonsmall cell lung cancer are to be based on cancer stage. Cancer staging for patients with resectable disease has been based on pathologic stage instead of preoperative clinical stage. However, the possibility of occult mediastinal lymph node metastases could lead to discrepancy between clinical and pathologic stage. While multi-modality treatments may be beneficial for patients with locally advanced disease, most studies have been based on clinical stage. The aim of this study was to identify the beneficial impact of neoadjuvant therapy and the prognostic value of final pathologic stage in these patients.
This study enrolled 530 lung cancer patients who received anatomic resection and mediastinal lymph node dissection at Chang Gung Memorial Hospital from January 2005 through June 2011. All resected specimens were examined by pathologists. Postoperative adjuvant therapies were given according to NCCN guideline recommendations. The clinico-pathologic factors of these patients were collected and analyzed.
Patients not receiving neoadjuvant therapy had a better probability of disease-free survival (P < 0.001) and overall survival (P = 0.0005), as well as a lower incidence of early relapse. Patients not receiving neoadjuvant therapy had a better disease-free survival rate in stages IA (P < 0.001), IB (P = 0.002), and IIB (P = 0.0117) from the point of view of final pathologic stage.
Patients receiving neoadjuvant therapy may experience a higher incidence of early relapse. Neoadjuvant therapy did not show definite benefits in the disease-free and overall survival rates from the point of view of final pathologic stage. Pathologic stage of nonsmall cell lung cancer patients who presented with resectable disease after neoadjuvant therapy did not predict the prognosis.
[Show abstract][Hide abstract] ABSTRACT: Background
COPD is an important public health challenge with significant heterogeneity of clinical presentation and disease progression. Clinicians have been trying to find phenotypes that may be linked to distinct prognoses and different therapeutic choices. Not all patients with COPD present with wheezing, a possible clinical phenotype that can help differentiate patient subgroups.
The Taiwan Obstructive Lung Disease study was a retrospective, multicenter research study to investigate the treatment patterns of COPD after the implementation of the Global Initiative for Chronic Obstructive Lung Disease 2011 guidelines. Between November 2012 and August 2013, medical records were retrieved from patients with COPD aged ≥40 years; patients diagnosed with asthma were excluded. Demographic data, lung function, symptom scores, and acute exacerbation were recorded and analyzed, and the differences between patients with and without wheezing were evaluated.
Of the 1,096 patients with COPD, 424 (38.7%) had the wheezing phenotype. The wheezing group had significantly higher COPD Assessment Test scores (12.4±7.8 versus 10.5±6.7, P<0.001), higher modified Medical Research Council grade (2.0±1.0 versus 1.7±0.9, P<0.001), and more acute exacerbations within the past year (0.9±1.3 versus 0.4±0.9, P<0.001) than the nonwheezing group. The postbronchodilator forced expiratory volume in 1 second was lower in wheezing patients (1.2±0.5 L versus 1.5±0.6 L, P<0.001). Even in patients with maintenance treatment fitting the Global Initiative for Chronic Obstructive Lung Disease 2011 guidelines, the wheezing group still had worse symptom scores and more exacerbations.
Wheezing is an important phenotype in patients with COPD. Patients with COPD having the wheezing phenotype are associated with worse symptoms, more exacerbations, and worse lung function.
Preview · Article · Oct 2015 · International Journal of COPD
[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.
Preview · Article · Sep 2015 · International Journal of COPD
[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.
No preview · Article · Aug 2015 · Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer
[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.
[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.
Full-text · Article · May 2015 · Critical care (London, England)