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Background The aim of the study was to assess programmed death‐ligand‐1 (PD‐L1) expression in different histological types and gene mutation status of patients with non‐small cell lung cancer (NSCLC). Methods A total of 4062 pathology‐confirmed lung cancer patients were retrospectively screened at Kaohsiung Chang Gung Memorial Hospital from November 2010 to June 2017. There were 699 NSCLC patients with confirmed PD‐L1 expression level retrospectively enrolled for analysis. Results There was a trend of higher PD‐L1 expression in squamous cell carcinoma and adenosquamous cell carcinoma than in adenocarcinoma (p = 063). Significant higher PD‐L1 expression in EGFR wild‐type was noted (p, A trend or significant differences in PD‐L1 expression between different histologic types in NSCLC, different EGFR status, and different ALK status, and different tumor tissue storage time. A higher survival benefit (TTF or OS) was observed in no PD‐L1 expression than with PD‐L1 expression in adenocarcinoma, EGFR mutation, and ALK mutation patients. PD‐L1 assay should be performed as early as possible if tissue is available.

Purpose To investigate the survival benefit with first/second generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) and osimertinib in different treatment sequences. Methods We retrospectively screened 3807 patients diagnosed with cancer between 2013 and 2019 at Kaohsiung Chang Gung Memorial Hospital. In total, 76 patients with EGFR T790M mutation who received osimertinib after re‐biopsy or liquid biopsy were enrolled for the analysis. Results The median progression‐free survival (PFS), median overall survival (OS), and median OS2 of the 76 patients were 11.93, 66.53, and 29.57 months, respectively. A significant difference was observed in the disease control rate between those who received osimertinib treatment after chemotherapy (group A) and those who received osimertinib immediately following EGFR‐TKI therapy (group B) (34 [94.4%] vs. 31 [77.5%], p = 0.036). In addition, chronic obstructive pulmonary disease tended to be a poor prognostic factor for PFS and OS. Conclusion This real‐world analysis revealed that previous chemotherapy could affect the treatment outcomes of patients with non‐small cell lung cancer treated with osimertinib. Osimertinib treatment following first/second generation EGFR‐TKI treatment or chemotherapy resulted in improved survival benefit., Osimertinib treatment after one line of chemotherapy (group A) had a better response rate and a better PFS than osimertinib treatment immediately following treatment with first/second generation EGFR‐TKIs (group B). COPD tended to a poor prognostic factor for PFS and OS2 in patients with osimertinib use.

The aim of this study is to determine the roles of global histone acetylation (Ac)/methylation (me), their modifying enzymes, and gene-specific histone enrichment in obstructive sleep apnea (OSA). Global histone modifications, and their modifying enzyme expressions were assessed in peripheral blood mononuclear cells from 56 patients with OSA and 16 matched subjects with primary snoring (PS). HIF-1α gene promoter-specific H3K36Ac enrichment was assessed in another cohort (28 OSA, 8 PS). Both global histone H3K23Ac and H3K36Ac expressions were decreased in OSA patients versus PS subjects. H3K23Ac expressions were further decreased in OSA patients with prevalent hypertension. HDAC1 expressions were higher in OSA patients, especially in those with excessive daytime sleepiness, and reduced after more than 6 months of continuous positive airway pressure treatment. H3K79me3 expression was increased in those with high C-reactive protein levels. Decreased KDM6B protein expressions were noted in those with a high hypoxic load, and associated with a higher risk for incident cardiovascular events or hypertension. HIF-1α gene promoter-specific H3K36Ac enrichment was decreased in OSA patients versus PS subjects. In vitro intermittent hypoxia with re-oxygenation stimuli resulted in HDAC1 over-expression and HIF-1α gene promoter-specific H3K36Ac under-expression, while HDAC1 inhibitor, SAHA, reversed oxidative stress through inhibiting NOX1. In conclusions, H3K23/H3K36 hypoacetylation is associated with the development of hypertension and disease severity in sleep-disordered breathing patients, probably through up-regulation of HDAC1, while H3K79 hypermethylation is associated with higher risk of cardiovascular diseases, probably through down-regulation of KDM6B.

Background The diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is complex, and the modality of treatment is surgery and targeted medication. Patients with CTEPH could have a poor prognosis if their diagnosis or treatment is delayed. The incidence of CTEPH and its clinical features are largely unknown in Taiwan, even among other Asian populations. In this study, we aimed to investigate the geodemographics of CTEPH in Taiwan and describe the practical management and treatment outcomes in patients with CTEPH. Methods This study retrospectively enrolled patients in the Taiwan cohort – Registry of CTEPH. The study was conducted over 2 years inclusive of follow-up. The enrolment criteria depended on the current global guideline. Results From January 2018 to March 2020, 107 CTEPH patients enrolled in the Taiwan registry. All patients received right heart catheterisation examinations. The overall median age was 61.4 ± 16.5 years, and the cohort was dominated by female patients (75/107). Risk factors included pulmonary embolism (81.3%), deep vein thrombosis (22.4%), and previous major surgery (20.6%). Twenty-one (19.6%) patients underwent pulmonary endarterectomy operation alone, and 38 (35.5%) patients underwent balloon pulmonary angioplasty alone. Conclusion To our knowledge, this is the first national cohort study that demonstrated the raw CTEPH incidence in Taiwan. It also showed the CTEPH incidence between male and female patients in the Asian population was different from the Caucasian population.

Objectives Acute exacerbations (AEs) of chronic obstructive pulmonary disease (COPD) can affect health status, hospitalization and readmission rates, and disease progression. This study aimed to identify independent markers associated with COPD AEs. Methods This study included male patients with COPD and collected data regarding their AEs and baseline clinical parameters. Results We included 149 male patients. Among them, 58 were included in the year 0 high-AE group and 91 in the low-AE group. Multivariate analysis revealed that the high-AE group had higher white blood cell count, lower serum albumin level, and post-bronchodilator (BD) forced expiratory volume in one second (FEV1) (%) with a combined receiver operating characteristic curve (ROC) of 0.721 ( p < 0.001). Additionally, 34 patients were included in the year 1 high-AE group and 70 in the low-AE group ( p < 0.001). Multivariate analysis revealed that the high-AE group had higher platelet count, positive asthma history, and lower pre-BD FEV1 (%) with a combined ROC of 0.782 ( p < 0.001). Conclusion In male patients with COPD, baseline white blood cell count, albumin level, and post-BD FEV1 (%) were correlated with year 0 AE; on the other hand, baseline platelet count, positive asthma history, and pre-BD FEV1 (%) were associated with year 1 AE.

To investigate the changes of blood pressure (BP) on patients with obstructive sleep apnea/hypopnea syndrome (OSA) before and after upper airway surgery.Case series with chart review.Tertiary academic medical center.Patients with OSA who underwent upper airway surgery were enrolled. We retrospectively investigated the nighttime and daytime BP before and at least 3 months after OSA surgery. PairedIn total, 176 patients with OSA (149 men, 27 women; mean age, 42.9 years; mean apnea/hypopnea index, 43.1/h) were enrolled in this study. The overall nighttime and daytime BP decreased significantly before and after OSA surgery (daytime systolic BP was reduced from 137.3 ± 14.0 mm Hg to 132.7 ± 17.0 mm Hg,Surgical modifications of the upper airways for patients with OSA could benefit blood pressure.

Nontuberculous mycobacterial lung disease (NTM-LD) prevalence has been increasing over the recent decades. Numerous host factors are associated with NTM-LD development, including susceptible phenotypes such as ciliary defect and lung structural change, pulmonary clearance defect with poor clearance of secretions, and immune suppression. Specifically, regarding the susceptible host phenotypes without clear pathogenesis, a slender body, pectus excavatum, and postmenopausal female status are common. Also, decreased host immunity to NTM, especially T helper 1 cell responses is frequently observed. Even so, the underlying mechanisms remain unclear and relevant large-scale studies are lacking. Infections due to host genetics associated defects are mostly untreatable but rare in Asia, particularly Taiwan. Nevertheless, some risks for NTM-LD are controllable over disease progression. We suggest that clinicians first manage host factors and deal with the controllable characteristics of NTM-LD, followed by optimizing anti-NTM treatment. Further researches focusing on NTM-LD pathogenesis, especially the host-NTM interaction may advance understanding the nature of the disease and develop efficient therapeutic regimens.

Background. Myasthenia gravis (MG) is an immune-mediated disorder characterized by muscle fatigue and fluctuating weakness. Impairment in respiratory strength and endurance has been described in patients with generalized MG. We tested the hypothesis that respiratory muscle training (RMT) can improve functional outcomes and reduce fatigue in patients with MG. Methods. Eighteen patients with mild to moderate MG participated in this study. The training group underwent home-based RMT three times a week for 12 weeks. Sixteen patients with MG without RMT were enrolled as a disease control group. Lung function, autonomic testing, Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF), and functional outcome measurement by using quantitative myasthenia gravis (QMG) score and myasthenia gravis composite (MGC) scale were measured before and after the 12-week RMT. Results. The 12-week RMT significantly increased forced vital capacity (FVC) from 77.9±12.6% to 83.8±17.7% (p=0.03), forced expiratory volume in one second (FEV1) from 75.2±18.3% to 83.3±19.0% (p=0.002), and 6-minute walking distance from 403.4±72.2 m to 466.1±68.5 m (p=0.003). The QMG score improved from 9.6±4.1 to 8.1±4.3 (p=0.04) and the MGC scale from 4.4±3.5 to 2.7±2.9 (p=0.02). The fatigue score (MFSI-SF) reduced from 17.1±14.7 to 13.5±16.9 (p=0.03). Conclusion. The home-based RMT is an effective pulmonary function training for MG patients. The RMT can not only improve short-term outcomes but also reduce fatigue in patients with mild to moderate generalized MG.

Objective Obstructive sleep apnea/hypopnea syndrome (OSA) could compromise oxygenation of the optic nerve and cause glaucomatous optic neuropathy; there has been no study to investigate the microstructure changes of the optic nerve and retina in OSA patients before and after continuous positive airway pressure (CPAP) therapy. In this study, we assess whether treatment with CPAP might improve visual sensitivity and retinal thickness in patients with OSA. Methods Patients with OSA were prospectively recruited and referred for ophthalmologic evaluation at baseline and three months after CPAP treatment. Each patient underwent an ophthalmological exam, standard automated perimetry (SAP), and optical coherence tomography (OCT) exam. Peripapillary retinal nerve fiber layer (RNFL) and macular layer (ML) thickness parameters were measured. The SAP, RNFL, and ML thickness parameters before and after treatment were compared. Results A total of 32 OSA patients were consecutively enrolled. At baseline, the mean deviation (MD) of SAP was −2.15 ± 1.90 dB (dB). After CPAP treatment, the MD was −1.38 ± 1.37 dB (p = 0.017). Regarding the OCT parameters, the inferior quadrant and nasal-inferior sector of RNFL thickness significantly improved after treatment (p = 0.025 and 0.004, respectively). The ML thickness in the superior-inner sector, inferior-outer sector, nasal-outer sector, superior hemisphere, and inferior hemisphere were also significantly improved after treatment. Improvement of ML thickness in the superior-inner sector positively correlated with the apnea/hypopnea index (r = 0.405, p = 0.022) and desaturation index (r = 0.473, p = 0.006) on pre-treatment polysomnography. Conclusion The treatment of CPAP could improve visual sensitivity and increase retinal thickness in patients with OSA.

Dual blockade of the EGFR and VEGF pathways in EGFR-mutated metastatic non-small-cell lung cancer (NSCLC) is supported by preclinical and clinical data, yet the approach is not widely implemented. RELAY assessed erlotinib, an EGFR tyrosine kinase inhibitor (TKI) standard of care, plus ramucirumab, a human IgG1 VEGFR2 antagonist, or placebo in patients with untreated EGFR-mutated metastatic NSCLC.This is a worldwide, double-blind, phase 3 trial done in 100 hospitals, clinics, and medical centres in 13 countries. Eligible patients were aged 18 years or older (20 years or older in Japan and Taiwan) at the time of study entry, had stage IV NSCLC, with an EGFR exon 19 deletion (ex19del) or exon 21 substitution (Leu858Arg) mutation, an Eastern Cooperative Oncology Group performance status of 0 or 1, and no CNS metastases. We randomly assigned eligible patients in a 1:1 ratio to receive oral erlotinib (150 mg/day) plus either intravenous ramucirumab (10 mg/kg) or matching placebo once every 2 weeks. Randomisation was done by an interactive web response system with a computer-generated sequence and stratified by sex, geographical region, EGFR mutation type, and EGFR testing method. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This trial is registered at ClinicalTrials.gov, NCT02411448, and is ongoing for long-term survival follow-up.Between Jan 28, 2016, and Feb 1, 2018, 449 eligible patients were enrolled and randomly assigned to treatment with ramucirumab plus erlotinib (n=224) or placebo plus erlotinib (n=225). Median duration of follow-up was 20·7 months (IQR 15·8-27·2). At the time of primary analysis, progression-free survival was significantly longer in the ramucirumab plus erlotinib group (19·4 months [95% CI 15·4-21·6]) than in the placebo plus erlotinib group (12·4 months [11·0-13·5]), with a stratified hazard ratio of 0·59 (95% CI 0·46-0·76; p0·0001). Grade 3-4 treatment-emergent adverse events were reported in 159 (72%) of 221 patients in the ramucirumab plus erlotinib group versus 121 (54%) of 225 in the placebo plus erlotinib group. The most common grade 3-4 treatment-emergent adverse events in the ramucirumab plus erlotinib group were hypertension (52 [24%]; grade 3 only) and dermatitis acneiform (33 [15%]), and in the placebo plus erlotinib group were dermatitis acneiform (20 [9%]) and increased alanine aminotransferase (17 [8%]). Treatment-emergent serious adverse events were reported in 65 (29%) of 221 patients in the ramucirumab plus erlotinib group and 47 (21%) of 225 in the placebo plus erlotinib group. The most common serious adverse events of any grade in the ramucirumab plus erlotinib group were pneumonia (seven [3%]) and cellulitis and pneumothorax (four [2%], each); the most common in the placebo plus erlotinib group were pyrexia (four [2%]) and pneumothorax (three [1%]). One on-study treatment-related death due to an adverse event occurred (haemothorax after a thoracic drainage procedure for a pleural empyema) in the ramucirumab plus erlotinib group.Ramucirumab plus erlotinib demonstrated superior progression-free survival compared with placebo plus erlotinib in patients with untreated EGFR-mutated metastatic NSCLC. Safety was consistent with the safety profiles of the individual compounds in advanced lung cancer. The RELAY regimen is a viable new treatment option for the initial treatment of EGFR-mutated metastatic NSCLC.Eli Lilly.

The association between sepsis and segmented neutrophil-to-monocyte (SeMo) ratio is unclear. We postulated that an increase in dynamic SeMo ratio measurement can be applied in risk stratification. This retrospective study included 727 consecutive sepsis patients in medical intensive care units (ICUs), including a subpopulation of 153 patients. According to the leukocyte (white blood cell, WBC) count on day 3 (normal range, between 4,000/µL and 12,000/µL) and delta SeMo (value of SeMo ratio on day 3 minus value of SeMo ratio on day 1; normal delta SeMo

To identify standard clinical parameters that may predict the presence and severity of obstructive sleep apnea/hypopnea syndrome (OSA).Case series with chart review.Tertiary academic medical center.A total of 325 adult patients (274 men and 51 women; mean age, 44.2 years) with habitual snoring completed comprehensive polysomnography and anthropometric measurements, including modified Mallampati grade (also known as updated Friedman's tongue position [uFTP]), tonsil size grading, uvular length, neck circumference, waist circumference, hip circumference, and body mass index (BMI).When the aforementioned physical parameters were correlated singly with the apnea/hypopnea index (AHI), we found that sex, uFTP, tonsil size grading, neck circumference, waist circumference, hip circumference, thyroid-mental distance, and BMI grade were reliable predictors of OSA. When all important factors were considered in a multiple stepwise regression analysis, an estimated AHI can be formulated by factoring sex, uFTP, tonsil size grading, and BMI grade as follows: -43.0 + 14.1 × sex + 12.8 × uFTP + 5.0 × tonsil size + 8.9 × BMI grade. Severity of OSA can be predicted with a receiver operating characteristic curve. Predictors of OSA can be further obtained by the "OSA score."This study has distinguished the correlations between sex, uFTP, tonsil size, and BMI grade and the presence and severity of OSA. An OSA score might be beneficial in identifying patients who should have a full sleep evaluation.

Nutritional status affects the survival of patients with sepsis. This retrospective study analyzed the impact of body mass index (BMI) and modified nutrition risk in critically ill (mNUTRIC) scores on survival of these patients. Data of 1291 patients with sepsis admitted to the intensive care unit (ICU) were extracted. The outcomes were mortality, duration of stay, ICU stay, and survival curve for 90-day mortality. Logistic regression analysis was performed to examine the risk factors for mortality. Cytokine and biomarker levels were analyzed in 165 patients. The 90-day survival of underweight patients with low mNUTRIC scores was significantly better than that of normal-weight patients with low mNUTRIC scores (70.8% vs. 58.3%, respectively, p = 0.048). Regression model analysis revealed that underweight patients with low mNUTRIC scores had a lower risk of mortality (odds ratio = 0.557, p = 0.082). Moreover, normal-weight patients with low mNUTRIC scores had the lowest human leukocyte antigen DR (HLA-DR) level on days 1 (underweight vs. normal weight vs. overweight: 94.3 vs. 82.1 vs. 94.3, respectively, p = 0.007) and 3 (91.8 vs. 91.0 vs. 93.2, respectively, p = 0.047). Thus, being underweight may not always be harmful if patients have optimal clinical nutritional status. Additionally, HLA-DR levels were the lowest in patients with low survival.

Dysphagia has been reported to be associated with the descent of the hyolaryngeal complex. Further, suprahyoid muscles play a greater role than infrahyoid muscles in elevation of the hyolarngeal complex. Respiratory muscle training (RMT) can improve lung function, and expiratory muscle strength training can facilitate elevation of the hyoid bone and increase the motor unit recruitment of submental muscles during normal swallowing. This study aimed to investigate the surface electromyography (sEMG) of the swallowing muscles, bilaterally, and the effect of RMT on swallowing muscles in stroke patients with respiratory muscle weakness.Forty patients with first episode of unilateral stroke were included in this retrospective controlled trial. After exclusion of 11 patients with respiratory muscle strength stronger than 70% of the predicted value, 15 were allocated to the RMT group and 14 to the control group. However, eventually, 11 patients in RMT group and 11 patients in control group completed the study. The sEMG of the orbicularis oris, masseter, submental, and infrahyoid muscles were recorded during dry swallowing, water swallowing (2 mL), and forced exhalation against a threshold breathing trainer set at different intensities, at baseline and after 6-week RMT.Regarding the sEMG of submental muscles, there were significant between-group differences on the latency of the unaffected side (P = .048), significant change from baseline force on the unaffected side (P = .035), and significant between-side difference (P = .011) in the RMT group during dry swallowing. Significant change in the duration from baseline was observed on the affected side of the RMT group when blowing was set at 50% maximal expiratory pressure (MEP; P = .015), and on the unaffected side of the control group when blowing set at 15% MEP (P = .005). Significant difference was observed in the duration between 50% MEP and 15% MEP after 6-week program in the control group (P = .049).A 6-week RMT can improve the electric signal of the affected swallowing muscles with more effect on the unaffected side than on the affected side during dry swallowing. Furthermore, RMT with 50% MEP rather than 15% MEP can facilitate greater submental muscle activity on the affected side in stroke patients with respiratory muscle weakness.

We hypothesized that epigenetics is a link between smoking/allergen exposures and the development of Asthma and chronic obstructive pulmonary disease (ACO). A total of 75 of 228 COPD patients were identified as ACO, which was independently associated with increased exacerbations. Microarray analysis identified 404 differentially methylated loci (DML) in ACO patients, and 6575 DML in those with rapid lung function decline in a discovery cohort. In the validation cohort, ACO patients had hypermethylated PDE9A (+ 30,088)/ZNF323 (− 296), and hypomethylated SEPT8 (− 47) genes as compared with either pure COPD patients or healthy non-smokers. Hypermethylated TIGIT (− 173) gene and hypomethylated CYSLTR1 (+ 348)/CCDC88C (+ 125,722)/ADORA2B (+ 1339) were associated with severe airflow limitation, while hypomethylated IFRD1 (− 515) gene with frequent exacerbation in all the COPD patients. Hypermethylated ZNF323 (− 296) / MPV17L (+ 194) and hypomethylated PTPRN2 (+ 10,000) genes were associated with rapid lung function decline. In vitro cigarette smoke extract and ovalbumin concurrent exposure resulted in specific DNA methylation changes of the MPV17L / ZNF323 genes, while 5-aza-2′-deoxycytidine treatment reversed promoter hypermethylation-mediated MPV17L under-expression accompanied with reduced apoptosis and decreased generation of reactive oxygen species. Aberrant DNA methylations may constitute a determinant for ACO, and provide a biomarker of airflow limitation, exacerbation, and lung function decline.

The aim of this study is to explore the role of microRNAs (miR)-21/23a/146a/150/155 targeting the toll-like receptor pathway in active tuberculosis (TB) disease and latent TB infection (LTBI). Gene expression levels of the five miRs and predicted target genes were assessed in peripheral blood mononuclear cells from 46 patients with active pulmonary TB, 15 subjects with LTBI, and 17 non-infected healthy subjects (NIHS). THP-1 cell lines were transfected with miR-23a-3p mimics under stimuli with Mycobacterium TB-specific antigens. Both miR-155-5p and miR-150-5p gene expressions were decreased in the active TB group versus the NIHS group. Both miR-23a-3p and miR-146a-5p gene expressions were decreased in active TB patients with high bacterial burden versus those with low bacterial burden or control group (LTBI + NIHS). TLR2, TLR4, and interleukin (IL)10 gene expressions were all increased in active TB versus NIHS group. MiR-23a-3p mimic transfection reversed ESAT6-induced reduction of reactive oxygen species generation, and augmented ESAT6-induced late apoptosis and phagocytosis, in association with down-regulations of the predicted target genes, including tumor necrosis factor (TNF)-&alpha, TLR4, TLR2, IL6, IL10, Notch1, IL6R, BCL2, TGF-&beta, 1, SP1, and IRF1. In conclusion, the down-regulation of miR-23a-3p in active TB patients with high bacterial burden inhibited mononuclear cell function and phagocytosis through TLR4/TNF-&alpha, /TGF-&beta, 1/IL-10 signaling via targeting IRF1/SP1.

We hypothesized that Ventilator-Associated Event (VAE) within 28 days upon admission to medical intensive care units (ICUs) can be a predictor for poor outcomes in sepsis patients. We aimed to determine the risk factors and associated outcomes of VAE. A total of 453 consecutive mechanically ventilated (MV) sepsis patients were enrolled. Of them, 136 patients had immune profile study. Early VAE (

Objectives This study aims to explore the role of M2a polarization and formyl peptide receptor (FPR) regulation in the reactivation of Mycobacterium tuberculosis (Mtb) infection. Methods M1/M2a monocyte percentage and FPR1/2/3 protein expression of blood immune cells were measured in 38 patients with sputum culture (+) active pulmonary TB disease, 18 subjects with latent TB infection (LTBI), and 28 noninfected healthy subjects (NIHS) using flow cytometry method. Results M1 percentage was decreased in active TB versus either NIHS or LTBI group, while M2a percentage and M2a/M1 percentage ratio were increased. FPR1 expression on M1/M2a, FPR2 expression on M1, and FPR3 expression of M1 were all decreased in active TB versus LTBI group, while FPR1 over FPR2 expression ratio on NK T cell was increased in active TB versus either NIHS or LTBI group. In 11 patients with active TB disease, M1 percentage became normal again after anti-TB treatment. In vitro Mtb-specific antigen stimulation of monocytic THP-1 cells resulted in M2a polarization in association with increased FPR2 expression on M2a. Conclusions Increased M2a and decreased M1 phenotypes of blood monocyte may serve as a marker for active TB disease, while decreased FPR1 on blood monocyte may indicate LTBI status.

Background: Long-acting muscarinic antagonist (LAMA) monotherapy is recommended for chronic obstructive pulmonary disease (COPD) patients with high risk of exacerbations. It is unclear whether long-acting β2-agonist (LABA)/LAMA fixed-dose combinations (FDCs) are more effective than LAMAs alone in preventing exacerbations. The aim of this study was to systematically review the literature to investigate whether LABA/LAMA FDCs are more effective than LAMA monotherapy in preventing exacerbations. Methods: We searched several databases and manufacturers’ websites to identify relevant randomized clinical trials comparing LABA/LAMA FDC treatment with LAMAs alone ⩾24 weeks. Outcomes of interest were time to first exacerbation and rates of moderate to severe, severe and all exacerbations. Results: We included 10 trials in 9 articles from 2013 to 2018 with a total of 19,369 patients for analysis in this study. Compared with LAMA monotherapy, LABA/LAMA FDCs demonstrated similar efficacy in terms of time to first exacerbation [hazard ratio, 0.96; 95% confidence interval (CI) 0.79–1.18; p = 0.71], moderate to severe exacerbations [risk ratio (RR), 0.96; 95% CI 0.90–1.03; p = 0.28], severe exacerbations (RR, 0.92; 95% CI 0.81–1.03; p = 0.15), and a marginal superiority in terms of all exacerbations (RR, 0.92; 95% CI 0.86–1.00; p = 0.04). The incidence of all exacerbation events was lower in the LABA/LAMA FDC group for the COPD patients with a history of previous exacerbations and those with a longer treatment period (52–64 weeks). Conclusion: This study provides evidence that LABA/LAMA FDCs are marginally superior in the prevention of all exacerbations compared with LAMA monotherapy in patients with COPD. The reviews of this paper are available via the supplemental material section.

To use computer-assisted quantitative measurements of upper airway changes during drug-induced sleep endoscopy (DISE) and to correlate these parameters with disease severities and physiologic changes in patients with obstructive sleep apnea/hypopnea syndrome (OSA).A retrospective study.Tertiary academic medical center.A total of 170 patients who failed continuous positive airway pressure therapy and then underwent upper airway surgery were enrolled. All patients received polysomnography and DISE preoperatively. We used ImageJ 1.48v to obtain maximal and minimal measurements, including cross-sectional areas and anterior-posterior and lateral diameters at 4 anatomic levels (retropalatal, oropharyngeal, retroglossal, and retroepiglottic) under DISE, and then computed the percentage changes. We analyzed the clinical values of DISE changes by computer-assisted analysis in patients with OSA and any correlations between these changes and polysomnography parameters.The percentage changes of upper airway showed significant collapses at all 4 anatomic levels (allComputer-assisted quantitative analysis could evaluate upper airway changes of OSA in an objective way and may help identify the sites of obstruction during DISE more accurately. Upper airway showed multilevel collapse with independent significant changes in patients with OSA, with the retropalatal and retroglossal levels playing important roles in particular.

ObjectiveDepression is a common comorbidity in cancer patients. This study aimed to compare the prevalence and associated factors of depressive disorder between patients with head and neck cancer (HNC) and those with lung cancer (LC).DesignThis study used a cross-sectional design with consecutive sampling.SettingA medical centre (Kaohsiung Chang Gung Memorial Hospital, Taiwan).ParticipantsPatients for the study were recruited from the HNC and LC outpatient clinic and inpatient ward from March 2016 to February 2018. Patients with HNC and LC were enrolled and assessed using the Mini International Neuropsychiatric Interview (MINI).Primary and secondary outcome measuresThe primary outcome was psychiatric diagnoses assessed using the MINI. The secondary outcomes were psychological well-being assessed using the Beck Anxiety Inventory, Taiwanese Depression Questionnaire, Brief Fatigue Inventory, Numeric Pain Rating Scale and the List of Threatening Experiences Questionnaire.ResultsIn total, 113 HNC patients and 104 LC patients were recruited for the study. The most common psychiatric comorbidity of HNC patients was alcohol use disorder (49.6%), followed by adjustment disorder (20.4%) and depressive disorder (11.5%). The most common psychiatric comorbidity of LC patients was depressive disorder (25.0%), followed by adjustment disorder (17.3%), alcohol use disorder (3.8%) and insomnia disorder (3.8%). Among HNC patients, a self-harm history was positively associated with depression (OR=11.91; 95% CI, 1.47 to 96.83), and a higher educational level was negatively associated with depression (OR=0.77; 95% CI, 0.66 to 0.91). Among LC patients, severity of stressor (OR=2.78; 95% CI, 1.50 to 5.15) and severity of anxiety (OR=1.18; 95% CI, 1.04 to 1.34) were two significant factors associated with depression.ConclusionWe reported the prevalence and associated factors of depression between patients with HNC and those with LC. Clinicians should be aware of this comorbidity and the associated risk factors, and conduct intervention programmes to prevent these cancer patients from developing depression.

MINI: In this study, respiratory function at the time of extubation can be useful optimal clinical guidelines for weaning and extubation attempts in patients with acute cervical spinal cord injury. Serum thiobarbituric acid-reactive substances level at admission can be a useful predictor for severity in acute cervical patients with spinal cord injury.Patients who had suffered from acute blunt cervical spinal cord injury (SCI) and admitted our hospital within 24 hours after injury were included in the study.We compared the respiratory function and serum reactive oxidative stress (ROS) after acute cervical SCI, and tried to find out the valuable predictors of weaning in patients with acute cervical SCI.Ventilation impairment is a major complication of acute cervical SCI. Evidence of oxygen radical formation in secondary injury from animal SCI models demonstrates an immediate postinjury increase in ROS production after SCI. We hypothesize that the serum ROS is associated with the severity of patients with acute cervical SCI.Thirty-eight adult patients who had acute cervical SCI and 58 healthy volunteers were enrolled. Respiratory function at admission, at the time of extubation and at 48 hours after extubation, serum oxidative stress, Injury Severity Score and Japanese Orthopaedic Association score at admission were compared.The most notable predictor of mechanical ventilation more than 48 hours was serum thiobarbituric acid-reactive substances (TBARS) level at admission (P = 0.027), and the cut-off value of serum TBARS level was 731.7 μmol/L (sensitivity 87.5% and specificity 78.9%). For the reventilation ≤5 days, the notable predictors were respiratory function at the time of extubation (maximal inspiratory pressure, P = 0.040; maximal expiratory pressure, P = 0.020; and tidal volume, P = 0.036) and serum TBARS level at admission (P = 0.013), the cut-off value of serum TBARS level at admission was 762.3 μmol/L (sensitivity 100% and specificity 90.0%).In this study, respiratory function (maximal inspiratory pressure, maximal expiratory pressure, and tidal volume) at the time of extubation can be useful optimal clinical guidelines for weaning and extubation attempts in patients with acute cervical SCI. Serum TBARS level at admission can be a useful predictor for severity in acute cervical SCI patients.3.Patients who had suffered from acute blunt cervical spinal cord injury (SCI) and admitted our hospital within 24 hours after injury were included in the study. We compared the respiratory function and serum reactive oxidative stress (ROS) after acute cervical SCI, and tried to find out the valuable predictors of weaning in patients with acute cervical SCI. Ventilation impairment is a major complication of acute cervical SCI. Evidence of oxygen radical formation in secondary injury from animal SCI models demonstrates an immediate postinjury increase in ROS production after SCI. We hypothesize that the serum ROS is associated with the severity of patients with acute cervical SCI. Thirty-eight adult patients who had acute cervical SCI and 58 healthy volunteers were enrolled. Respiratory function at admission, at the time of extubation and at 48 hours after extubation, serum oxidative stress, Injury Severity Score and Japanese Orthopaedic Association score at admission were compared. The most notable predictor of mechanical ventilation more than 48 hours was serum thiobarbituric acid-reactive substances (TBARS) level at admission (P = 0.027), and the cut-off value of serum TBARS level was 731.7 μmol/L (sensitivity 87.5% and specificity 78.9%). For the reventilation ≤5 days, the notable predictors were respiratory function at the time of extubation (maximal inspiratory pressure, P = 0.040; maximal expiratory pressure, P = 0.020; and tidal volume, P = 0.036) and serum TBARS level at admission (P = 0.013), the cut-off value of serum TBARS level at admission was 762.3 μmol/L (sensitivity 100% and specificity 90.0%). In this study, respiratory function (maximal inspiratory pressure, maximal expiratory pressure, and tidal volume) at the time of extubation can be useful optimal clinical guidelines for weaning and extubation attempts in patients with acute cervical SCI. Serum TBARS level at admission can be a useful predictor for severity in acute cervical SCI patients. Level of Evidence: 3.

Comparative long-term efficacy of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) for prevention of disease progression to hepatocellular carcinoma (HCC) among high-risk patients with chronic hepatitis B (CHB)-related compensated cirrhosis is controversial.To compare the long-term efficacy of ETV and TDF in HCC prevention in patients with CHB-related cirrhosis, and to evaluate predictive risk factors for HCC development.From January 2008 to March 2018, 894 treatment-naïve patients with CHB-related compensated cirrhosis on ETV or TDF were enrolled based on the longitudinal cohort study. Data were originally collected for 7.3 years of follow-up or after the launch of TDF in 2011. Only the 5-year cumulative incidence and risk factors of HCC were assessed.Total 678 and 216 patients received ETV and TDF, respectively. The cumulative risk of HCC at 1, 3 and 5 years of follow-up was 1.6%, 11.3% and 18.7%, respectively, in the ETV group; and 0.9%, 6.7% and 10.7%, respectively, in the TDF group (P = 0.0305). Univariate and adjusted-multivariable models revealed that platelet count, alpha-fetoprotein (AFP) levels and upper gastrointestinal (UGI) varices were independent risk factors for HCC development. TDF resulted in risk of HCC development compared to ETV with adjusted hazard ratios (aHRs) of 0.66 (95% confidence interval [CI]:0.40, 1.08; P = 0.0971), 0.69 (95% CI: 0.42, 1.14; P = 0.1488) and 0.66 (95% CI: 0.38, 1.14; P = 0.1407) under stepwise selection, propensity score adjustment, and propensity score matching multivariable models, respectively.For treatment-naïve patients with CHB-related compensated cirrhosis with 5-year follow-up, after variable adjustments, propensity score approaches and subgroup analyses, TDF showed a lower rate of HCC development that did not reach statistical significance, compared to the ETV.

Obstructive sleep apnea (OSA) is a syndrome leading to chronic intermittent hypoxia, and the up-regulation of toll-like receptors (TLR) 2 and 6 on peripheral blood cells has been reported. We hypothesized that DNA methylation in TLR2 and TLR6 genes may play a role in the development of OSA and its excessive daytime sleepiness (EDS) phenotype. DNA methylation over 28 cytosine-phosphate-guanine (CpG) sites of the TLR2 promoter region and 3 CpG sites of the TLR6 gene body, and their protein expressions were measured by using pyrosequencing and ELISA methods in 18 heathy subjects (HS) and 58 patients with severe OSA (divided into 18 non-EDS and 40 EDS group). Patients with severe OSA had higher DNA methylation levels over five CpG sites (#1, #2, #3, #25 and #28) and lower DNA methylation levels over CpG site #18 of the TLR2 promoter region, higher DNA methylation levels over two CpG sites (#1 and #3) of the TLR6 gene body, and higher protein expressions of TLR6 than HS. The CpG site #2 of the TLR6 gene body was hypermethylated in severe OSA patients with EDS. Both DNA methylation levels over CpG site #1 of the TLR6 gene body and protein expressions of TLR6 were reduced after more than 6 months of nasal CPAP treatment in seven selected patients. Aberrant DNA methylation of the TLR2 promoter region and TLR6 gene body are associated with the consequence of severe OSA and its EDS phenotype.

Introduction: Onsite scoring is common in traditional OSCEs although there is the potential for an audience effect facilitating or inhibiting performance. We aim to (1) analyze the reliability between onsite scoring (OS) and remote scoring (RS); and (2) explore the factors that affect the scoring in different locations. Methods: A total of 154 students and 84 raters were enrolled in a single-site during 2013-2015. We selected six stations randomly from a 12-station national high-stakes OSCE. We applied generalisability theory for the analysis and investigated the perceptions that affected RS scoring. Results: The internal consistency reliability Cronbach's α of the checklists was 0.92. The kappa agreement was 0.623 and the G value was 0.93. The major source of variance comes from the students themselves, but some from locations and raters. The three-component analysis including Technical Feasibility, Facilitates Wellbeing, and Observational and Attention Deficits explained 73.886% of the total variance in RS scoring. Conclusions: Our study has demonstrated moderate agreement and good reliability between OS and RS ratings. We validated the factors of facility operation and quality for RS raters. Remote scoring can provide an alternative forum for the raters to overcome the barriers of distance, space, and avoid the audience effect.

Introduction: The aim of this study was to evaluate the effects of upper airway surgery on daytime sleepiness in nonobese patients with obstructive sleep apnea/hypopnea syndrome (OSA). Methods: This retrospective study included 121 consecutive adult nonobese patients with OSA from a tertiary academic medical center. Patients with OSA who refused continuous positive airway pressure therapy, or in whom it was unsuccessful, and then underwent OSA surgery were enrolled. Evaluations of excessive daytime sleepiness using the Epworth Sleepiness Scale (ESS) and major parameters of objective full-night polysomnography were collected preoperatively and at least 3 months postoperatively. Statistical analysis was performed using the Wilcoxon signed rank test and Wilcoxon rank sum test. Results: When pre- and postoperative ESS and polysomnographic parameters were compared in all patients, ESS scores, apnea/hypopnea index, and snoring index showed statistically significant improvements ( P = .007, P < .001, and P < .001, respectively). When patients were classified into mild, moderate, and severe OSA groups, snoring index had statistically significant improvements in all 3 groups, and apnea/hypopnea index had statistically significant decreases in the moderate and severe OSA groups. Although reductions in ESS scores were found in all 3 groups, the most statistically significant improvement was noted only in the severe OSA group. Conclusions: OSA surgery can improve daytime sleepiness in nonobese patients with OSA, especially for patients with severe OSA. This study elucidates the effects of OSA surgery on daytime sleepiness by excluding the major confounding factor of obesity. This study adds to the literature on the effects of upper airway surgery for nonobese patients with OSA on daytime quality of life.

Objective: To develop an adequate model using reliable clinical and physical factors to predict pediatric obstructive sleep apnea/hypopnea syndrome (OSAS). Methods: Complete anthropometric measurements including BMI z score, tonsil size grading, and updated Friedman tongue position (uFTP) were evaluated. Subjective assessments of clinical symptoms/signs, including snoring visual analog scale (VAS), nasal obstruction, and mouth breathing, were recorded. Results: Eighty-eight children (57 boys and 31 girls, mean age = 9.0 years) were confirmed to have OSAS by comprehensive polysomnography (PSG). When the aforementioned variables were analyzed individually, the results indicated that snoring VAS, nasal obstruction, mouth breathing, and BMI z score were reliable predictors of apnea/hypopnea index (AHI/h) values (correlation coefficient r = 0.386, P < .001; r = 0.416, P < .001; r = 0.255, P = .02; and r = 0.243, P = .02, respectively). When all significant factors were included in the stepwise multiple linear regression analysis, the final predictive model is: Pediatric AHI = 0.108 + 0.103 snoring VAS + 0.894 nasal obstruction + 0.207 BMI z score ( F = 4.06, P = .01). Conclusion: The proposed noninvasive, simple, inexpensive, and easy to perform screening tool could be used to predict pediatric OSAS. An abnormal calculated AHI may prompt clinical physicians to conduct further PSG diagnostics and treatment.

We intended to develop a scoring system to predict mechanical ventilator dependence in patients who survive sepsis/septic shock with respiratory failure. This study evaluated 251 adult patients in medical intensive care units (ICUs) between August 2013 to October 2015, who had survived for over 21 days and received aggressive treatment. The risk factors for ventilator dependence were determined. We then constructed a ventilator dependence (VD) risk score using the identified risk factors. The ventilator dependence risk score was calculated as the sum of the following four variables after being adjusted by proportion to the beta coefficient. We assigned a history of previous stroke, a score of one point, platelet count less than 150,000/μL a score of one point, pH value less than 7.35 a score of two points, and the fraction of inspired oxygen on admission day 7 over 39% as two points. The area under the curve in the derivation group was 0.725 (p

Body mass index (BMI) influences the prognosis of patients with non-small cell lung cancer (NSCLC), including both early-stage and late-stage NSCLC patients that are undergoing chemotherapies. However, earlier research on the relationship between BMI and survival in patients taking epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) yielded contradictory results. These publications either had a limited number of patients or were getting TKIs in various lines of therapy, which might explain why the outcomes were contradictory. As a result, we undertook retrospective study to examine the effect of BMI on survival outcomes in patients with advanced EGFR mutant NSCLC receiving first-line EGFR-TKIs. We also compared the findings to those with wild-type EGFR. Between November 2010 and March 2014, 513 patients with advanced NSCLC were enrolled in the study. According to the adjusted BMI cut-off point for Asia, 35 out of 513 (6.8%) patients were underweight (BMI &lt, 18.5 kg/m2), whereas 197 (38.4%) were overweight (BMI &gt, 24 kg/m2). Overweight patients with wild-type EGFR exhibited longer progression-free survival (4.6 vs. 2.1 months, p = 0.003) and overall survival (OS) (8.9 vs. 4.3 months, p = 0.003) than underweight patients. Overweight patients with EGFR mutations had a longer OS than normal-weight patients (23.0 vs. 20.2 months, p = 0.025). Bodyweight reduction was related to a shorter OS in both the mutant EGFR patients (17.1 vs. 30.5 months, p &lt, 0.001) and the wild-type EGFR patients (7.8 vs. 18.7 months, p &lt, 0.001). In conclusion, advanced stages NSCLC patients with a lower BMI and early weight loss had a worse outcome that was independent of EGFR mutation status.

// Yung-Che Chen 1, 6, * , Meng-Chih Lin 1, 6, * , Chang-Chun Hsiao 6, 7 , Yi-Xin Zheng 1 , Kuang-Den Chen 2 , Ming-Tse Sung 3 , Chung-Jen Chen 4 , Ting-Ya Wang 1 , Yong-Yong Lin 1 , Huang-Chih Chang 1, 6 , Yu-Mu Chen 1 and Jen-Chieh Chang 5 1 Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 2 Center of Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 3 Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 4 Division of Rheumatology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 5 Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 6 Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan 7 Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan * These authors have contributed equally to this work Correspondence to: Yung-Che Chen, email: yungchechen@yahoo.com.tw Meng-Chih Lin, email: linmengchih@hotmail.com Chang-Chun Hsiao, email: cchsiao@mail.cgu.edu.tw Keywords: lung adenocarcinoma, S100A15, DNA methylation, next generation sequencing Received: November 02, 2016 Accepted: April 10, 2017 Published: April 24, 2017 ABSTRACT Purpose : This study aims to determine the functional role of S100A15 and its promoter DNA methylation patterns in lung cancer progression. Experimental Design : We analyzed 178 formalin-fixed paraffin embedded specimens from lung cancer patients, including 24 early stage and 91 advanced stage adenocarcinoma. S100A15 protein expression was evaluated by immunohistochemistry stain, and its DNA methylation levels were measured by pyrosequencing. Results : S100A15 nuclear staining was increased in lung adenocarcinoma patients with distant metastasis versus those without distant metastasis. There was reduced one/three-year overall survival in adenocarcinoma patients receiving first line target therapy and harboring high nuclear expressions of S100A15. Both DNA methylation levels over -423 and -248 CpG sites of the S100A15 gene promoter were decreased in adenocarcinoma patients with distant metastasis, and the former was associated with lower one-year overall survival. The highly invasive CL1-5 cell lines display decreased DNA methylation over –412/-248/-56 CpG sites of the S100A15 gene promoter and increased S100A15 gene/protein expressions as compared with the less invasive CL1-0 cell lines. Knockdown of S100A15 in CL1-5 cell line inhibited cell proliferation, migration, and invasion, while over-expression of S100A15 in CL1-0 cell line promoted cell proliferation, migration, and invasion. RNA sequencing analysis revealed potential biological effects of S100A15 over-expression and knock-down with CTNNB1, ZEB1, CDC42, HSP90AA1, BST2, and PCNA being the pivotal down-stream mediators. Conclusions : Increased S100A15 expression and decreased DNA methylation of its gene promoter region were associated with high metastasis potential and poor outcome in lung adenocarcinoma, probably through triggering CTNNB1 -centered pathways.

Acquired resistance occurs in most non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations experiencing a response to EGFR-tyrosine kinase inhibitor (TKI) initially. We investigated EGFR-TKI retreatment in patients who had previously received EGFR-TKI followed by chemotherapy.This was a retrospective multicenter study. Patients with locally advanced or metastatic adenocarcinoma or TTF-1 (+) NSCLC, positive EGFR sensitive mutation, and EGFR-TKI reuse after initial EGFR-TKI followed by chemotherapy were enrolled. The objectives were to assess the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) of EGFR TKI switched retreatment.In total, 205 patients were enrolled, with a median age of 61.8 years (range 31.4-92.9). There was a larger proportion of females (62.9%) than males, and more never-smokers (73.2%) than ever-smokers. In the initial EGFR-TKI administration, 57.6% of patients showed a complete response (CR) or partial response (PR), and 34.6% had stable disease (SD); in the second-line chemotherapy, 13.7% had PR, and 58.0% had SD; in the EGFR-TKI retreatment, 7.3% had PR, and 37.1% had SD. The median PFS of first-line EGFR-TKI was 8.0 months (95% CI 7.3-8.2), and retreatment EGFR-TKI was 4.1 months (95% CI 2.7-4.6). The median OS since the start of the first-line EGFR-TKI therapy was 35.9 months (95% CI 28.8-50.9), and since the start of EGFR-TKI retreatment was 12.6 months (95% CI 10.4-20.9). In the univariable and multivariable regression analysis of factors associated with PFS of EGFR-TKI retreatment, time interval between the two EGFR TKIs equal to or more than 7 months was statistically significant (HR=0.62, 95% CI 0.44-0.86; HR=0.6, 95% CI 0.43-0.86), both p0.01. Females with exon 21 mutation also showed a significant difference between the two groups (HR=0.51, 95% CI 0.30-0.86; HR=0.52 (0.31-0.88), both p0.05).EGFR-TKI retreatment was effective in prolonging survival, and was shown to be a worthwhile option for EGFR-mutated NSCLC patients after failure of first-line EGFR-TKI and chemotherapy. The survival benefit was especially pronounced in patients with longer drug holidays from the initial EGFR-TKI and in females with the exon 21 mutation.

Osimertinib is a third-generation, irreversible tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing andIn this trial, we randomly assigned 556 patients with previously untreated advanced NSCLC with anThe median overall survival was 38.6 months (95% confidence interval [CI], 34.5 to 41.8) in the osimertinib group and 31.8 months (95% CI, 26.6 to 36.0) in the comparator group (hazard ratio for death, 0.80; 95.05% CI, 0.64 to 1.00; P = 0.046). At 3 years, 79 of 279 patients (28%) in the osimertinib group and 26 of 277 (9%) in the comparator group were continuing to receive a trial regimen; the median exposure was 20.7 months and 11.5 months, respectively. Adverse events of grade 3 or higher were reported in 42% of the patients in the osimertinib group and in 47% of those in the comparator group.Among patients with previously untreated advanced NSCLC with an

Osimertinib is a third-generation, irreversible tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations. A phase 3 trial compared first-line osimertinib with other EGFR-TKIs in patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). The trial showed longer progression-free survival with osimertinib than with the comparator EGFR-TKIs (hazard ratio for disease progression or death, 0.46). Data from the final analysis of overall survival have not been reported. In this trial, we randomly assigned 556 patients with previously untreated advanced NSCLC with an EGFR mutation (exon 19 deletion or L858R allele) in a 1:1 ratio to receive either osimertinib (80 mg once daily) or one of two other EGFR-TKIs (gefitinib at a dose of 250 mg once daily or erlotinib at a dose of 150 mg once daily, with patients receiving these drugs combined in a single comparator group). Overall survival was a secondary end point. The median overall survival was 38.6 months (95% confidence interval [CI], 34.5 to 41.8) in the osimertinib group and 31.8 months (95% CI, 26.6 to 36.0) in the comparator group (hazard ratio for death, 0.80; 95.05% CI, 0.64 to 1.00; P = 0.046). At 3 years, 79 of 279 patients (28%) in the osimertinib group and 26 of 277 (9%) in the comparator group were continuing to receive a trial regimen; the median exposure was 20.7 months and 11.5 months, respectively. Adverse events of grade 3 or higher were reported in 42% of the patients in the osimertinib group and in 47% of those in the comparator group. Among patients with previously untreated advanced NSCLC with an EGFR mutation, those who received osimertinib had longer overall survival than those who received a comparator EGFR-TKI. The safety profile for osimertinib was similar to that of the comparator EGFR-TKIs, despite a longer duration of exposure in the osimertinib group. (Funded by AstraZeneca; FLAURA ClinicalTrials.gov number, NCT02296125.).

Pneumonia leads to changes in body composition and weakness due to the malnourished condition. In addition, patient family caregivers always have a lack of nutritional information, and they do not know how to manage patients&rsquo, nutritional intake during hospitalization and after discharge. Most intervention studies aim to provide nutritional support for older patients. However, whether long-term nutritional intervention by dietitians and caregivers from patients&rsquo, families exert clinical effects&mdash, particularly in malnourished pneumonia&mdash, on nutritional status and readmission rate at each interventional phase, from hospitalization to postdischarge, remains unclear. To investigate the effects of an individualized nutritional intervention program (iNIP) on nutritional status and readmission rate in older adults with pneumonia during hospitalization and three and six months after discharge. Eighty-two malnourished older adults with a primary diagnosis of pneumonia participated. Patients were randomly allocated to either a nutrition intervention (NI) group or a standard care (SC) group. Participants in the NI group received an iNIP according to energy and protein intake requirements in addition to dietary advice based on face-to-face interviews with their family caregivers during hospitalization. After discharge, phone calls were adopted for prescribing iNIPs. Anthropometry (i.e., body mass index, limb circumference, and subcutaneous fat thickness), blood parameters (i.e., albumin and total lymphocyte count), hospital stay, Mini-Nutritional Assessment-Short Form (MNA-SF) score, target daily calorie intake, total calorie intake adherence rate, and three-major-nutrient intakes were assessed during hospitalization and three and six months after discharge. Both groups received regular follow-up through phone calls. Furthermore, the rate of readmission resulting from pneumonia was recorded after discharge. During hospital stay, the NI group showed significant increases in daily calorie intake, total calorie intake adherence rate, and protein intake compared with the SC group (p &lt, 0.05), however, no significant difference was found in anthropometry, blood biochemical values, MNA-SF scores, and hospital stay. At three and six months after discharge, the NI group showed significantly higher daily calorie intake and MNA-SF scores (8.2 vs. 6.5 scores at three months, 9.3 vs. 7.6 scores at six months) than did the SC group (p &lt, 0.05). After adjusting for sex, the readmission rate for pneumonia significantly decreased by 77% in the NI group compared with that in the SC group (p = 0.03, OR: 0.228, 95% CI: 0.06&ndash, 0.87). A six-month iNIP under dietitian and patient family nutritional support for malnourished older adults with pneumonia can significantly improve their nutritional status and reduce the readmission rate.

This study is designed to investigate the effects of obstructive sleep apnea/hypopnea syndrome (OSA) surgery on serum leptin levels and metabolic disturbances, both of which contribute to the risk of cardiovascular diseases.Case series with planned data collection.Tertiary referral medical center.A retrospective chart review of 101 consecutive patients with OSA who refused or failed conservative therapy and who then underwent upper airway surgery for OSA treatment was conducted. The personal medical history, anthropometric measurements, subjective symptoms, and objective polysomnographic parameters and fasting morning blood samples for leptin and metabolic biomarkers measurements were collected preoperatively and at a minimum of 3 months postoperatively.Eighty patients with OSA (69 men and 11 women; mean [SD] age of 42.2 [10.2] years) with complete data were included in the final analysis. At least 3 months after surgery, serum leptin, low-density lipoprotein cholesterol (LDL-C), and triglyceride levels and the mean systolic blood pressure (SBP) (night and morning) significantly decreased. According to the classical definition of surgical success, 40 subjects had successful surgery and were categorized as surgical responders, and the other 40 patients who failed surgery were categorized as surgical nonresponders. Significant reductions in serum leptin, total cholesterol, LDL-C, and triglyceride levels and improvement of mean SBP (morning) occurred in surgical responders but not in nonresponders.Effective OSA surgery improves serum leptin, lipid profiles, and SBP. Further studies are needed to investigate the role of serial measurements of these biomarkers in monitoring surgical outcome of OSA treatment.

Background/Purpose There is a lack of data on nivolumab treatment outcomes in Taiwanese patients with advanced or recurrent non-small cell lung cancer (NSCLC) ineligible for radical radiotherapy and resistant to platinum-based chemotherapy. We investigated the safety and efficacy of nivolumab in this population. Methods In this ongoing, multicenter, open-label, single-arm, phase II study, patients aged ≥20 years with a performance status of 0–1 and stage IIIB/IV or recurrent NSCLC received nivolumab 3 mg/kg every 2 weeks in 6-week cycles. Interim data obtained between 27 January 2016 and 21 May 2017 were analyzed. Safety, based on adverse event (AE) reporting, was the primary endpoint. Efficacy assessment parameters included overall response rate (ORR), overall survival (OS), and progression-free survival (PFS). Results Among 53 treated patients with advanced NSCLC (median age 61.0 years; 62.3% male), mean treatment duration was 99.7 days. AEs (any grade) and serious AEs were reported by 92.5% and 47.2% of patients, respectively. Adverse drug reactions (ADRs; any) occurred in 58.5% of patients; grade ≥3 ADRs occurred in 13.2% of patients. Five deaths occurred; two cases (neoplasm progression and septic shock) were considered treatment-emergent. Common ADRs were fatigue (17.0%) and rash (13.2%). Common immune-related treatment-emergent AEs were rash (17.0%) and pruritus (13.2%). The centrally assessed ORR was 9.4% (5/53). The median OS and median PFS were 11.5 months and 1.4 months, respectively. Conclusion Nivolumab appeared to be safe and effective in Taiwanese patients. These interim results suggest that nivolumab is a suitable treatment option for this population. Clinical trial registration NCT02582125.

ObjectiveThe aim of this study was to determine whether do-not-resuscitate (DNR) orders affect outcomes in patients with sepsis admitted to intensive care unit (ICU).DesignThis is a retrospective observational study.ParticipantsWe enrolled 796 consecutive adult intensive care patients at Kaohsiung Chang Gung Memorial Hospital, a 2700-bed tertiary teaching hospital in southern Taiwan. A total of 717 patients were included.Main measuresClinical factors such as age, gender and other clinical factors possibly related to DNR orders and hospital mortality were recorded.Key resultsThere were 455 patients in the group without DNR orders and 262 patients in the group with DNR orders. Within the DNR group, patients were further grouped into early (orders signed on intensive care day 1, n=126) and late (signed after day 1, n=136). Patients in the DNR group were older and more likely to have malignancy than the group without DNR orders. Mortality at days 7, 14 and 28, as well as intensive care and hospital mortality, were all worse in these patients even after propensity-score matching. There were higher Charlson Comorbidity Index in the emergency room, but better outcomes in those with early-DNR orders compared with late-DNR orders.ConclusionsDNR orders may predict worse outcomes for patients with sepsis admitted to medical ICUs. The survival rate in the early-DNR order group was not inferior to the late-DNR order group.

Objective: Obstructive sleep apnea/hypopnea syndrome (OSA) could compromise oxygenation of the optic nerve and cause glaucomatous optic neuropathy; however, there were no studies to investigate the changes of visual function and retinal microstructures in OSA patients after upper airway surgery. We aim to assess the changes in the visual sensitivity and retinal fiber layer thickness in OSA patients before and after surgery. Methods: This prospective single-blind study enrolled patients with OSA from a tertiary academic medical center who had unsuccessful conservative therapy and then underwent surgery. The patients were referred for comprehensive ophthalmologic evaluation at baseline and 6 months after OSA surgery. The polysomnographic findings were collected pre- and postoperatively. Visual sensitivities on standard automated perimetry (SAP) were assessed. Peripapillary retinal nerve fiber layer (RNFL) thickness and macular layer (ML) thickness parameters were measured by spectral-domain optical coherence tomography (OCT). Results: A total of 108 OSA patients were enrolled. Six months after surgery, the major parameters of polysomnography (PSG), mean deviation, and pattern standard deviation of SAP significantly improved in these OSA patients. Regarding the OCT parameters, thickness of ML in the nasal-outer, superior-inner, temporal-inner, inferior-inner, nasal-inner sectors, and total ML thickness significantly increased 6 months after upper airway surgery in the severe OSA group (apnea/hypopnea index ⩾30 per hour). Conclusion: The visual sensitivities on SAP, ML thickness on OCT, and oxygenation status on PSG significantly improved 6 months after upper airway surgery in patients with severe OSA. Upper airway surgery may ameliorate the microstructures of the retina in patients with severe OSA.

Adenotonsillectomy is recommended for children who need surgery for obstructive sleep apnea syndrome (OSAS). Overnight, polysomnography (PSG) is suggested for post-surgery follow-up, but this diagnostic technique is time consuming and inconvenient. Desaturation index (DI) has been reported as a good tool for predicting both the presence and severity of OSAS in children. The purpose of this study was to determine the usefulness of the DI for post-surgery follow-up of children with OSAS. This retrospective study enrolled 42 children, aged 3–12 years, who were snorers diagnosed with OSAS by overnight PSG and who underwent an adenotonsillectomy. Pre- and postoperative PSG parameters, nocturnal pulse oximetry data, and modified Epworth sleepiness scale scores were assessed. Previously determined cut-off DI values (2.05, 3.50, and 4.15 for mild, moderate, and severe OSAS, respectively) were used to predict residual OSAS. Of the 42 children, obvious improvements were observed in apnea-hypopnea index (AHI, decreased 45.5 %), arousal index (decreased 30.5 %), DI (decreased 40.4 %), and snore index (decreased 100.3 %) compared with the preoperative measurements. Among these objective PSG measures, DI had the strongest correlation with AHI both pre- and post-surgeries (r = 0.947 and r = 0.954, respectively; p all

Background Clinically, multidrug-resistant Acinetobacter baumannii (MDR-AB) recurrence is found in some patients although identified as successfully eradicated. We aim to discover the characteristics of patients with MDR-AB recurrence in the respiratory tract. Methods We retrospectively collected 106 chronic respiratory failure patients with MDR-AB harvest in pulmonary secretion culture. Results MDR-AB was successfully eradicated in 69 patients. Diabetes mellitus (p = 0.030, odds ratio [OR]: 2.7, 95% confidence interval [CI]: 1.1–6.4) and acute respiratory distress syndrome (p = 0.001, OR = 4.8, 95% CI: 1.8–12.7) reduce the MDR-AB eradication rate. Besides, a classification of colonization or infection was made beyond the 69 MDR-AB eradicated patients. In the colonization group, diabetes mellitus (p = 0.009; OR = 5.1, 95% CI: 1.5–17.6) is the only independent factor to increase the recurrence rate. Glycated hemoglobin level is also analyzed for each group to investigate diabetes control effect, but no significant difference found. Conclusions Diabetes mellitus is a risk factor of MDR-AB recurrence among MDR-AB-colonized patients; the impact of localized pneumonia patch in MDR-AB-infected patients requires further study to be clarified.

In daily practice, some patients with certain clinical characteristics may have better responses to the administration of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs). It is therefore reasonable to stratify and weigh the importance of these clinical parameters which may not only affect patients' responses to TKIs but also progression-free survival (PFS) other than the impact of EGFR mutation status per se.This retrospective study evaluated EGFR-mutant, non-small cell lung cancer patients who received EGFR-TKIs as a first-line therapy between January 2011 and December 2013. Several potential prognostic factors were analyzed with respect to PFS, and the results of this analysis were validated in another time cohort.A total of 262 patients were included in the study. Age ≤ 40 years, uncommon EGFR mutations, poor performance status, more sites of distal metastasis, and blood lymphocyte to monocyte ratio ≤ 3 were independently associated with poor PFS. These five factors were included in a scoring system and three prognostic groups A, B, and C, were formed based on total scores of 0-1, 2, and ≥ 3, respectively. In the test group, the PFS was 15.7 month, 9.3 month, and 4.0 month in groups A, B, and C, respectively (p0.001). Between the test and validation groups, no significant differences were found in each one of the three prognostic groups.The scoring system appears valid and reproducible for PFS prognosis in EGFR-mutant patients who received first-line EGFR-TKIs.

Depressed baroreflex sensitivity (BRS) have been reported in patients with obstructive sleep apnea (OSA). This study aimed to determine if surgery can improve the clinical outcomes by investigating changes in BRS and in other cardiovascular autonomic parameters.Eighty-one OSA patients were enrolled. They were classified as mild OSA if their apnea-hypopnea index (AHI) was 5-15, moderate OSA if their AHI was 15-30, and sever OSA if their AHI was30. Twenty-three subjects with AHI5 were recruited as controls. For patients who received surgery, polysomnography (PSG) and autonomic tests were evaluated upon enrollment and six-months after surgery.The patient number for mild, moderate, and severe OSA was 22, 22, and 37, respectively. BRS on enrollment showed significant difference among the four groups, with the highest BRS in the control group, follow by the mild, moderate, and severe OSA groups. There were significant correlations between BRS and all PSG parameters. The depressed BRS significantly improved after surgery.Surgical modifications of the upper airways can improve the depressed BRS in OSA patients.The study offers the promise that surgical treatment for OSA not only improves the index of PSG, but also reduces the possibility of cardiovascular risk.

The purpose of this study is to explore the anti-inflammatory role of microRNAs (miR)-21 and miR-23 targeting the TLR/TNF-&alpha, pathway in response to chronic intermittent hypoxia with re-oxygenation (IHR) injury in patients with obstructive sleep apnea (OSA). Gene expression levels of the miR-21/23a, and their predicted target genes were assessed in peripheral blood mononuclear cells from 40 treatment-naive severe OSA patients, and 20 matched subjects with primary snoring (PS). Human monocytic THP-1 cell lines were induced to undergo apoptosis under IHR exposures, and transfected with miR-21-5p mimic. Both miR-21-5p and miR-23-3p gene expressions were decreased in OSA patients as compared with that in PS subjects, while TNF-&alpha, gene expression was increased. Both miR-21-5p and miR-23-3p gene expressions were negatively correlated with apnea hypopnea index and oxygen desaturation index, while TNF-&alpha, gene expression positively correlated with apnea hypopnea index. In vitro IHR treatment resulted in decreased miR-21-5p and miR-23-3p expressions. Apoptosis, cytotoxicity, and gene expressions of their predicted target genes&mdash, including TNF-&alpha, ELF2, NFAT5, HIF-2&alpha, IL6, IL6R, EDNRB, and TLR4&mdash, were all increased in response to IHR, while all were reversed with miR-21-5p mimic transfection under IHR condition. The findings provide biological insight into mechanisms by which IHR-suppressed miRs protect cell apoptosis via inhibit inflammation, and indicate that over-expression of the miR-21-5p may be a new therapy for OSA.

Jui-O Chen,1,2,* Jui-Fang Liu,1,3–5,* Yu-qi Liu,6 Yu-Mu Chen,7 Mei-Lien Tu,4 Hong-Ren Yu,8 Meng-Chih Lin,3,7 Chiu-Chu Lin,2 Shih-Feng Liu3,7 1Department of Nursing, Tajen University, Pingtung, Taiwan; 2College of Nursing, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Department of Respiratory Therapy, Kaohsiung Chang Gung Memorial Hospital-Kaohsiung Medical Center and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 4Respiratory Care, Chang Gung University of Science and Technology, Taoyuan, Taiwan; 5Department of Education, National Kaohsiung Normal University, Kaohsiung, Taiwan; 6Department of Intensive Care unit, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China; 7Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 8Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan *These authors contributed equally to this work Purpose: It is unclear whether the effectiveness of pulmonary rehabilitation program (PRP) after cardiac surgery differs between patients with and without COPD. This study aimed to compare the effectiveness of PRP between patients with and without COPD undergoing coronary artery bypass graft (CABG) surgery. Patients and methods: We retrospectively included patients who underwent CABG surgery and received 3-week PRP from January 2009 to December 2013. We excluded patients who underwent emergency surgery, had an unstable hemodynamic status, were ventilator dependent or did not complete the PRP. Demographics, muscle strength, degree of dyspnea, pulmonary function and postoperative complications were compared. Results: Seventy-eight patients were enrolled (COPD group, n=40; non-COPD group, n=38). Maximal inspiratory pressure (MIP; −34.52 cmH2O vs −43.25 cmH2O, P

Background/purpose: It is controversial whether healthcare-associated pneumonia (HCAP) belongs to a unique clinical entity or it shares common characteristics with community-acquired pneumonia (CAP). The impact of prior pulmonary tuberculosis (PTB) in clinical presentation and treatment outcome of ICU-admitted CAP and HCAP patients also remains unknown. Methods: We report a nationwide, multi-center, retrospective study. ICU-admitted CAP and HCAP patients from six medical centers in Taiwan were enrolled for analysis. Patients were defined as either CAP or HCAP cases, and with and without prior PTB, according to the database of Taiwan CDC. The disease severity, microbiologic characteristics, and treatment outcomes between CAP and HCAP patients with or without prior PTB were compared and analyzed. Results: A total of 414 ICU-admitted patients, including 176 CAP cases and 238 HCAP cases were included for analysis during the study period. In both CAP and HCAP subgroups, the pneumonia severities, proportions of organ dysfunction, and microbiologic characteristics were similar between patients with and without prior PTB. In survival analysis, patients with prior PTB had higher 30-day mortality than those without prior PTB (38.9% vs. 16.5%, p = 0.021) in the CAP population. Multivariate analysis revealed that a history of prior PTB was an independent clinical factor associated with higher 30-day mortality rate in CAP patients (HR = 4.45, 95% CI: 1.81–10.98, P = 0.001). Conclusion: History of prior PTB is an independent clinical factor for increased 30-day mortality rate in ICU-admitted CAP patients, but not in ICU-admitted HCAP patients. Keywords: Community-acquired pneumonia, Healthcare-associated pneumonia, Intensive care unit, Mortality, Tuberculosis

Background Asthma is a heterogeneous disease with complex mechanisms and involves many risk factors and in vivo cellular molecules. It is notable that sex differences may have a potential effect on asthma phenotype. Objective To identify sex-specific phenotypes and health outcomes of asthma. Methods We conducted the Taiwanese Adult Asthma Cohorts study to enroll female (n = 421) and male (n = 299) adult patients with stable asthma. Eight variables were selected by a factor analysis. We further performed a 2-step sensitivity cluster analysis to classify asthma clusters. The risks of asthma-related outcomes among the clusters were assessed using simple logistic regressions. Results Three different clusters were identified in males and females. In the female clusters, atopy/eosinophil-predominant (cluster 2), and obesity/neutrophil-predominant pattern (cluster 3) had more than a 2-fold risk of asthma exacerbations (odds ratio, 2.51; 95% CI, 1.12-5.59 and odds ratio, 2.22; 95% CI, 1.01-4.93). In the male clusters, current smoker/neutrophilic atopic cluster (cluster 5) and ex-smoker/eosinophil-predominant or mixed inflammatory pattern (cluster 6) also had a higher risk of asthma exacerbations. Conclusions This study identified heterogeneous characteristics between sexes. In females, the analysis showed atopy with eosinophil-predominant and obese with neutrophil-predominant inflammation. Two distinct asthma phenotypes were found in current and ex-smokers in males. Understanding asthma phenotypes and explaining the potentially biological pathways have become important.

Objective: To retrospectively study the effects of minimally invasive single-stage multilevel surgery (MISS MLS) for treating patients with obstructive sleep apnea/hypopnea syndrome (OSA) on quality of life (QOL). Methods: All OSA patients with multilevel obstruction who failed or refused continuous positive airway pressure (CPAP) treatment and then underwent Pillar implants and temperature-controlled radiofrequency of the base of tongue (RFBOT) were enrolled. The subjective symptoms and QOL (SF-36 Taiwan Standard Version 1.0) parameters were collected preoperatively and a minimum of 3 months postoperatively. Postoperative morbidity and complications were also recorded. Results: Thirty-seven patients (30 men, 7 women; mean age = 46.8 years; mean BMI = 23.9 kg/m2) were enrolled. The mean Epworth Sleepiness Scale changed from 12 ± 4.3 to 10.6 ± 4.3 ( P = .004, Wilcoxon signed-rank test). The mean snoring visual analog scale reduced from 9.5 ± 1.3 to 4.0 ± 2.0 ( P < .0001). The mean score of SF-36 increased from 65.5 ± 19.6 to 75.2 ± 16.7 ( P = .001). The SF-36 subscales showed statistically significant changes, especially in bodily pain, role-emotional, and general health. Conclusion: The study demonstrated that MISS MLS was effective on QOL in selected patients for treating OSA patients who are unresponsive to conservative OSA therapy.

Context • Obstructive sleep apnea/hypopnea syndrome (OSAHS) is among the most prevalent of sleep-related breathing disorders. No long-term follow-up studies have documented the continued success of lifestyle changes in treatment; oral appliances have an approximate 50% success rate; compliance with continuous positive airway pressure is poor, ranging from 50% to 89%; and the success rate of upper-airway surgery is only 66.4%. Therefore, some OSAHS patients seek alternative treatments. Objectives • The study intended to examine the efficacy of traditional Chinese therapeutic massage (tui na) for patients with OSAHS. Design • The research team designed a prospective study. Setting • The study took place at the outpatient clinic of the sleep center at the Kaohsiung Chang Gung Memorial Hospital (Kaohsiung, Taiwan), an academic tertiary medical center. Participants • Participants were 31 patients with moderate to severe OSAHS. Intervention • Each participant received a tui na treatment at multiple acupoints 2 ×/wk for 10 wk for approximately 15 min/session. Outcome Measures • At baseline and 3 mo after treatment, participants completed subjective measures, including (1) quality of life using a 36-item, short-form health survey (SF-36); (2) subjective snoring intensity indicated by bed-partners using a 0-10 visual analog scale (VAS); and (3) excessive daytime sleepiness (EDS) status, using a Chinese version of the Epworth Sleepiness Scale (CESS). The research team completed objective measures, including (1) polysomnography, (2) body mass index, and (3) neck circumference. Results • Twenty patients completed the full course of treatment. The apnea/hypopnea index per hour decreased from 43.8 ± 26.9 to 37.8 ± 31.7 after the treatments, with P = .049 (paired t test). The arousal index and rapid eye movement stage of sleep improved significantly. Statistically significant improvements were observed for the SF-36 on the score for the physical component summary, for its subscale for general health, for the mental component summary, and for 2 of its subscales: vitality and mental health. The VAS and the CESS showed that snoring intensity and EDS decreased significantly, respectively. No major complications occurred. Conclusions • Tui na is a feasible and safe treatment for patients with OSAHS. It can improve the quality of life, sleep architecture, snoring intensity, and EDS in patients with moderate-to-severe OSAHS. In the future, a controlled study should be considered to further investigate the effects of tui na for OSAHS.

Background Immunoparalysis was observed in both patients with cancer and sepsis. In cancer patients, Cytotoxic T lymphocyte antigen-4 and programmed cell death protein 1/programmed death-ligand 1 axis are two key components of immunoparalysis. Several emerging therapies against these two axes gained significant clinical benefit. In severe sepsis patients, immunoparalysis was known as compensatory anti-inflammatory response syndrome and this has been suggested as an important cause of death in patients with sepsis. It would be interesting to see if immune status was different in severe sepsis patients with or without active cancer. The aim of this study was to assess the differences in immune profiles, and clinical outcomes between severe sepsis patients with or without cancer admitted to ICU. Methods A combined retrospective and prospective observational study from a cohort of adult sepsis patients admitted to three medical ICUs at Kaohsiung Chang Gung Memorial Hospital in Taiwan between August 2013 and June 2016. Results Of the 2744 patients admitted to the ICU, 532 patients with sepsis were included. Patients were divided into those with or without active cancer according to their medical history. Of the 532 patients, 95 (17.9%) patients had active cancer, and 437 (82.1%) patients had no active cancer history. Patients with active cancer were younger (p = 0.001) and were less likely to have diabetes mellitus (p < 0.001), hypertension (p < 0.001), coronary artery disease (p = 0.004), chronic obstructive pulmonary disease (p = 0.002) or stroke (p = 0.002) compared to patients without active cancer. Patients with active cancer also exhibited higher baseline lactate levels (p = 0.038), and higher baseline plasma interleukin (IL)-10 levels (p = 0.040), higher trend of granulocyte colony-stimulating factor (G-CSF) (p = 0.004) compared to patients without active cancer. The 14-day, 28-day and 90-day mortality rates were higher for patients with active cancer than those without active cancer (P < 0.001 for all intervals). Conclusions Among patients admitted to the ICU with sepsis, those with underling active cancer had higher baseline levels of plasma IL-10, higher trend of G-CSF and higher mortality rate than those without active cancer.

Liver metastasis has been found to affect outcome in prostate cancer and colorectal cancer, but its role in lung cancer is unclear. The current study aimed to evaluate the impact of de novo liver metastasis (DLM) on stage IV non-small cell lung cancer (NSCLC) outcomes and to examine whether tyrosine kinase inhibitors (TKI) reverse poor prognosis in patients with DLM and epidermal growth factor receptor (EGFR)-mutant NSCLC. Among 1392 newly diagnosed NSCLC patients, 490 patients with stage IV disease treated between November 2010 and March 2014 at Kaohsiung Chang Gung Memorial Hospital were included. Patients were divided into two groups according to DLM status. There were 75 patients in the DLM group and 415 patients in the non-DLM group. The DLM group included more patients with bone metastasis, fewer patients with a lymphocyte-to-monocyte ratio (LMR) > 3.1, and fewer patients with pleural metastasis. In the DLM group, Eastern Cooperative Oncology Group performance status 3–4 and LMR ≦3.1 were associated with poor outcome. In patients without DLM, overall survival (OS) was longer in patients with EGFR-mutant NSCLC than in those without (20.2 vs. 7.3 months, p < 0.001). Among DLM patients, OS was similar between the EGFR-mutant and wild-type EGFR tumor subgroups (11.9 vs. 7.7 months, p = 0.155). We found that DLM was a significant poor prognostic factor in the EGFR-mutant patients treated with EGFR-TKIs, whereas DLM did not affect the prognosis of EGFR-wild-type patients.