Meta-analysis of genome-wide association studies identifies multiple lung cancer susceptibility loci in never-smoking Asian women.

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.

First-Line Erlotinib Therapy Until and Beyond Response Evaluation Criteria in Solid Tumors Progression in Asian Patients With Epidermal Growth Factor Receptor Mutation-Positive Non-Small-Cell Lung Cancer: The ASPIRATION Study.

Importance: Continuing molecularly targeted treatment beyond disease progression in non-small-cell lung cancer (NSCLC) has appeared promising in retrospective analyses, highlighting the challenge to identify whether progression is the optimal time to switch treatment.

Objective: To study the efficacy of first-line erlotinib therapy in patients with NSCLC with activating EGFR mutations and postprogression erlotinib therapy.

Design, Setting, And Participants: ASPIRATION (Asian Pacific trial of Tarceva as first-line in EGFR mutation) was a phase 2, open-label, single-arm study conducted from 2011 to 2012 in 23 centers in Hong Kong, Korea, Taiwan, and Thailand of adults with stage IV, EGFR mutation-positive NSCLC, with ECOG performance status 0 to 2.

Severe Sepsis and Septic Shock: Timing of Septic Shock Onset Matters.

Introduction: Timing of septic shock onset may play a prognostic role in severe sepsis; however, clinical evidence provides contradictory results. This study aimed to investigate possible associations between timing of onset of septic shock and patient outcome.

Methods: In a university-affiliated hospital, all patients admitted to the intensive care unit (ICU) for severe sepsis or septic shock from November 2007 to March 2011 were included.

COPD in Taiwan: a National Epidemiology Survey.

Objectives: To determine the prevalence of COPD in Taiwan and to document the disease characteristics and associated risk factors.

Methods: We conducted a random cross-sectional national survey of adults older than 40 years in Taiwan. Respiratory health screening questions identified subjects with diagnosed COPD or whose reported symptoms also fulfilled an epidemiological case definition; these were eligible to complete the survey, which also included indices of symptom severity and disability and questions on comorbidities, medical treatments, smoking habits, and occupations potentially harmful to respiratory health.

EGFR mutation and lobar location of lung adenocarcinoma.

The objective of this study was to investigate the associations among lung cancer location, and epidermal growth factor receptor (EGFR) mutation status. Treatment-naive, pathologically confirmed lung adenocarcinomas with tumor specimens available for genetic analysis were included from 2011 through 2014. Overall, 1771 patients with lung adenocarcinoma were included for analysis, after excluding those with carcinoma not otherwise specified, or synchronous multiple primary lung cancers.

Epidemiology and Outcome of Severe Sepsis and Septic Shock in Surgical Intensive Care Units in Northern Taiwan.

Severe sepsis remains the leading cause of mortality in the critically ill. Local epidemiological studies on sepsis are of paramount importance to increase our knowledge about sepsis features and to improve patient care and prognosis.Adult patients (≥20 years) admitted to the surgical intensive care units with severe sepsis or septic shock from 2009 to 2010 were retrospectively retrieved and analyzed.

Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types.

Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.

Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients.

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

Despite 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.

Effect of Tracheostomy on Weaning Parameters in Difficult-to-Wean Mechanically Ventilated Patients: A Prospective Observational Study.

Background And Objective: Weaning parameters are commonly measured through an endotracheal tube in mechanically ventilated patients recovering from acute respiratory failure, however this practice has rarely been evaluated in tracheostomized patients. This study aimed to investigate changes in weaning parameters measured before and after tracheostomy, and to explore whether the data measured after tracheostomy were associated with weaning outcomes in difficult-to-wean patients.

Methods: In a two-year study period, we enrolled orotracheally intubated patients who were prepared for tracheostomy due to difficult weaning.

Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Non-Small-Cell Lung Cancer Patients with Leptomeningeal Carcinomatosis.

Background: Leptomeningeal carcinomatosis (LC) is a detrimental complication of patients with non-small-cell lung cancer (NSCLC). The effect of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) on the clinical outcome of these patients, particularly those with EGFR mutations, has not been studied yet.

Methods: We searched the database for lung cancer patients diagnosed from 2003 to 2010 in one Asian medical center.

Mycobacterium abscessus Complex Infections in Humans.

Mycobacterium abscessus complex comprises a group of rapidly growing, multidrug-resistant, nontuberculous mycobacteria that are responsible for a wide spectrum of skin and soft tissue diseases, central nervous system infections, bacteremia, and ocular and other infections. M. abscessus complex is differentiated into 3 subspecies: M.

Gender-Dimorphic Impact of PXR Genotype and Haplotype on Hepatotoxicity During Antituberculosis Treatment.

Women have a higher risk of drug-induced hepatotoxicity during antituberculosis treatment (HATT) than men. We hypothesized that single nucleotide polymorphism (SNP) genotype and derived haplotype of pregnane X receptor (PXR) gene, which could regulate the expression of phase I enzyme cytochrome P450 (CYP) 3A4, had a sex-specific influence on the risk of HATT. Six SNPs of the PXR gene were sequenced.

R331W Missense Mutation of Oncogene YAP1 Is a Germline Risk Allele for Lung Adenocarcinoma With Medical Actionability.

Purpose: Adenocarcinoma is the most dominant type of lung cancer in never-smoker patients. The risk alleles from genome-wide association studies have small odds ratios and unclear biologic roles. Here we have taken an approach featuring suitable medical actionability to identify alleles with low population frequency but high disease-causing potential.

Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6.

Background: Most patients with non-small-cell lung cancer tumours that have EGFR mutations have deletion mutations in exon 19 or the Leu858Arg point mutation in exon 21, or both (ie, common mutations). However, a subset of patients (10%) with mutations in EGFR have tumours that harbour uncommon mutations. There is a paucity of data regarding the sensitivity of these tumours to EGFR inhibitors.

Performance Assessment of the BluePoint MycoID Plus Kit for Identification of Mycobacterium tuberculosis, Including Rifampin- and Isoniazid-resistant Isolates, and Nontuberculous Mycobacteria.

The performance of the BluePoint MycoID plus kit (Bio Concept Corporation, Taichung, Taiwan), which was designed to simultaneously detect Mycobacterium tuberculosis (MTB), rifampin- and isoniazid-resistant MTB, and nontuberculous mycobacteria (NTM) was first evaluated with 950 consecutive positive cultures in Mycobacterium Growth Indicator Tube (MGIT) system (BACTEC, MGIT 960 system, Becton-Dickinson, Sparks) from clinical respiratory specimens. The discrepant results between kit and culture-based identification were finally assessed by 16S rRNA gene sequencing and clinical diagnosis. The accuracy rate of this kit for identification of all Mycobacterium species was 96.

Comparison of the Prevalence of Latent Tuberculosis Infection among Non-Dialysis Patients with Severe Chronic Kidney Disease, Patients Receiving Dialysis, and the Dialysis-Unit Staff: A Cross-Sectional Study.

Background: Patients with renal failure are vulnerable to tuberculosis, a common worldwide infectious disease. In the growing dialysis population, the risk for tuberculosis among the associated sub-groups is important but unclear. This study investigated latent tuberculosis infection (LTBI) in patients with severe chronic kidney disease (CKD) and among dialysis-unit staff caring for patients on dialysis.

Inhaled nitric oxide therapy and risk of renal dysfunction: a systematic review and meta-analysis of randomized trials.

Introduction: Inhaled nitric oxide (iNO) is an important therapy for acute respiratory distress syndrome (ARDS), pulmonary hypertension and pediatric hypoxemic respiratory failure. Safety concerns regarding iNO and renal dysfunction have been reported; however, there are currently no systematic reviews on this issue. Our objective was to evaluate published randomized controlled trials (RCTs) to ascertain the risk of renal dysfunction associated with iNO therapy in patients with and without ARDS.

Detection and Dynamic Changes of EGFR Mutations from Circulating Tumor DNA as a Predictor of Survival Outcomes in NSCLC Patients Treated with First-line Intercalated Erlotinib and Chemotherapy.

Purpose: Blood-based circulating-free (cf) tumor DNA may be an alternative to tissue-based EGFR mutation testing in NSCLC. This exploratory analysis compares matched tumor and blood samples from the FASTACT-2 study.

Experimental Design: Patients were randomized to receive six cycles of gemcitabine/platinum plus sequential erlotinib or placebo.

Identification of five driver gene mutations in patients with treatment-naïve lung adenocarcinoma in Taiwan.

Background: It is important to select appropriate targeted therapies for subgroups of patients with lung adenocarcinoma who have specific gene alterations.

Methods: This prospective study was a multicenter project conducted in Taiwan for assessment of lung adenocarcinoma genetic tests. Five oncogenic drivers, including EGFR, KRAS, BRAF, HER2 and EML4-ALK fusion mutations, were tested.

Clinical and prognostic implications of RET rearrangements in metastatic lung adenocarcinoma patients with malignant pleural effusion.

Objectives: RET rearrangements represent one of the newest molecular targets in non-small cell lung cancer (NSCLC). However, the prevalence, clinical characteristics, and outcome of patients with RET-rearranged lung adenocarcinoma in metastatic disease remain uncertain.

Materials And Methods: Multiplex reverse transcription-polymerase chain reaction (RT-PCR) was used to detect KIF5B-RET and CCDC6-RET fusions from specimens of malignant pleural effusion (MPE) in patients with metastatic lung adenocarcinoma.

Decreased serum level of lipoprotein cholesterol is a poor prognostic factor for patients with severe community-acquired pneumonia that required intensive care unit admission.

Purpose: The purpose of this study is to investigate the prognostic values of the serum levels of lipids in patients with severe community-acquired pneumonia (CAP) that required intensive care unit (ICU) admission.

Materials And Methods: Patients who had severe CAP that required ICU admission were included. Serum lipid level was collected on the days 1 and 7 of ICU stay.

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

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.

Estimated Creatinine Clearance Rate Is Associated With the Treatment Effectiveness and Toxicity of Pemetrexed As Continuation Maintenance Therapy for Advanced Nonsquamous Non-Small-Cell Lung Cancer.

Unlabelled: The purpose of this study was to explore the predictive factors of the effectiveness and treatment toxicity for pemetrexed as continuation maintenance therapy in patients with advanced nonsquamous non-small-cell lung cancer. Patients with an estimated creatinine clearance rate (Ccr) < 60 mL/min had a significantly longer survival. However, a decrease in estimated Ccr was associated with a increased risk of Grade 3/4 neutropenia and anemia.