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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.

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.

Background: First-line durvalumab plus etoposide with either cisplatin or carboplatin (platinum–etoposide) showed a significant improvement in overall survival versus platinum–etoposide alone in patients with extensive-stage small-cell lung cancer (ES-SCLC) in the CASPIAN study. Here we report updated results, including the primary analysis for overall survival with durvalumab plus tremelimumab plus platinum–etoposide versus platinum–etoposide alone. Methods: CASPIAN is an ongoing, open-label, sponsor-blind, randomised, controlled phase 3 trial at 209 cancer treatment centres in 23 countries worldwide. Eligible patients were aged 18 years or older (20 years in Japan) and had treatment-naive, histologically or cytologically documented ES-SCLC, with a WHO performance status of 0 or 1. Patients were randomly assigned (1:1:1) in blocks of six, stratified by planned platinum, using an interactive voice-response or web-response system to receive intravenous durvalumab plus tremelimumab plus platinum–etoposide, durvalumab plus platinum–etoposide, or platinum–etoposide alone. In all groups, patients received etoposide 80–100 mg/m2 on days 1–3 of each cycle with investigator's choice of either carboplatin area under the curve 5–6 mg/mL/min or cisplatin 75–80 mg/m2 on day 1 of each cycle. Patients in the platinum–etoposide group received up to six cycles of platinum–etoposide every 3 weeks and optional prophylactic cranial irradiation (investigator's discretion). Patients in the immunotherapy groups received four cycles of platinum–etoposide plus durvalumab 1500 mg with or without tremelimumab 75 mg every 3 weeks followed by maintenance durvalumab 1500 mg every 4 weeks. The two primary endpoints were overall survival for durvalumab plus platinum–etoposide versus platinum–etoposide and for durvalumab plus tremelimumab plus platinum–etoposide versus platinum–etoposide in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered at ClinicalTrials.gov, NCT03043872. Findings: Between March 27, 2017, and May 29, 2018, 972 patients were screened and 805 were randomly assigned (268 to durvalumab plus tremelimumab plus platinum–etoposide, 268 to durvalumab plus platinum–etoposide, and 269 to platinum–etoposide). As of Jan 27, 2020, the median follow-up was 25·1 months (IQR 22·3–27·9). Durvalumab plus tremelimumab plus platinum–etoposide was not associated with a significant improvement in overall survival versus platinum–etoposide (hazard ratio [HR] 0·82 [95% CI 0·68–1·00]; p=0·045); median overall survival was 10·4 months (95% CI 9·6–12·0) versus 10·5 months (9·3–11·2). Durvalumab plus platinum–etoposide showed sustained improvement in overall survival versus platinum–etoposide (HR 0·75 [95% CI 0·62–0·91]; nominal p=0·0032); median overall survival was 12·9 months (95% CI 11·3–14·7) versus 10·5 months (9·3–11·2). The most common any-cause grade 3 or worse adverse events were neutropenia (85 [32%] of 266 patients in the durvalumab plus tremelimumab plus platinum–etoposide group, 64 [24%] of 265 patients in the durvalumab plus platinum–etoposide group, and 88 [33%] of 266 patients in the platinum–etoposide group) and anaemia (34 [13%], 24 [9%], and 48 [18%]). Any-cause serious adverse events were reported in 121 (45%) patients in the durvalumab plus tremelimumab plus platinum–etoposide group, 85 (32%) in the durvalumab plus platinum–etoposide group, and 97 (36%) in the platinum–etoposide group. Treatment-related deaths occurred in 12 (5%) patients in the durvalumab plus tremelimumab plus platinum–etoposide group (death, febrile neutropenia, and pulmonary embolism [n=2 each]; enterocolitis, general physical health deterioration and multiple organ dysfunction syndrome, pneumonia, pneumonitis and hepatitis, respiratory failure, and sudden death [n=1 each]), six (2%) patients in the durvalumab plus platinum–etoposide group (cardiac arrest, dehydration, hepatotoxicity, interstitial lung disease, pancytopenia, and sepsis [n=1 each]), and two (1%) in the platinum–etoposide group (pancytopenia and thrombocytopenia [n=1 each]). Interpretation: First-line durvalumab plus platinum–etoposide showed sustained overall survival improvement versus platinum–etoposide but the addition of tremelimumab to durvalumab plus platinum–etoposide did not significantly improve outcomes versus platinum–etoposide. These results support the use of durvalumab plus platinum–etoposide as a new standard of care for the first-line treatment of ES-SCLC. Funding: AstraZeneca.

Background: To investigate the relationships among the clinical characteristics, different EGFR-TKIs, and osimertinib treatment in different treatment lines.Methods: We retrospectively screened a total of 3807 patients diagnosed between 2013 and 2019 at Kaohsiung Chang Gung Memorial Hospital. Furthermore, 98 patients after re-biopsy or liquid with EGFR T790M mutation who received osimertinib were enrolled for analysis. Results: Among all 98 patients, the median PFS of those who received osimertinib therapy was 10.48 months, and the median OS of those who received osimertinib therapy was 42.21 months. The OS of those who received osimertinib therapy after previous gefitinib, afatinib, or erlotinib therapy was 87.93, 49.00, and 42.00 months, respectively (P=0.006). There was a significant difference in disease control rate between those who received osimertinib treatment after previous chemotherapy (Group A) or immediately following EGFR-TKI therapy (Group B) (93.3% vs. 77.4%, P=0.029). There was also a significant difference in PS between those who received osimertinib as a second-line treatment and those who received it as a third-line treatment (10.83 vs. 17.33 months, P=0.044). In addition, COPD tended to be a poor prognostic factor for PFS and OS.Conclusion: In this retrospective real‐world analysis, it was determined that pretreatment with gefitinib and previous chemotherapy could affect the treatment outcomes of NSCLC patients treated with osimertinib. Furthermore, COPD tended to a poor prognostic factor for PFS and OS in such patients.

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.

Supplemental material, sj-pdf-1-tam-10.1177_17588359211018022 for The relative importance of predictive factors for single first-generation EGFR-TKI use for more than 5 years in patients with advanced non-small cell lung cancer: Taiwan multicenter TIPS-5 study by Yen-Hsiang Huang, Jen-Yu Hung, How-Wen Ko, Po-Lan Su, Chun-Liang Lai, Huang-Chih Chang, Te-Chun Hsia, Sheng-Hao Lin, Kuan-Li Wu, Cheng-Ta Yang, Wu-Chou Su, Yi-Chun Chu, Chin-Chou Wang, Wei-Yu Liao, Yen-Ting Lin, Ching-Hsiung Lin, Meng-Chih Lin, Kuo-Hsuan Hsu, Jeng-Sen Tseng, Tsung-Ying Yang, Kun-Chieh Chen, Mei-Hsuan Lee, Sung-Liang Yu, Chao-Chi Ho and Gee-Chen Chang in Therapeutic Advances in Medical Oncology

Background Sepsis-associated acute kidney injury (AKI) often worsens with the deterioration of a patient's condition. Therefore, we hypothesized that monitoring AKI dynamically from day1 to day 3 was potential to predict hospital mortality. Specifically, we explored whether monitoring AKI dynamically in the intensive care unit (ICU) could be a sepsis phenotype predictive of mortality. A new classification was established based on the change in the AKI stage from admission day 1 and day 3. We compared the hospital mortality, cytokines, and immune response pattern between each group. Material and methods We retrospectively enrolled 523 patients with sepsis, and we calculated the AKI stages on day 1 and day 3 admission to ICUs. Among these 523 people, 388 of them were assigned to normal, improved, and deteriorated groups according to the changes in the AKI stages. 263 of which did not develop AKI on day1 and day 3 (normal group). The AKI stage improved in 68 patients (improved group) and worsened in 57 (deteriorated group). We compared the mortality rates between the groups, and identified the relationship between the dynamic AKI status, immune response patterns, and cytokine levels. Results The hospital mortality rate in the deteriorated group was higher than that in the non-deteriorated group (combination of normal and improved group) (p = 0.004). Additionally, according to the Kaplan–Meier analysis, the non-deteriorated group had a distinct hospital survival curve (p = 0.004). Furthermore, both the overexpression of tumor necrosis factor-α and decreased monocyte expression of human leukocyte antigen-DR were present in the deteriorated group. Conclusions The deteriorated group was associated with a higher hospital mortality rate, potentially resulting from an abnormal inflammatory response. Worsening AKI in the first 3 days of ICU admission may be a sepsis phenotype predictive of hospital mortality.

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 (

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.

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.

// Chin-Chou Wang 1, 2, 3, * , Chia-Cheng Tseng 1, 4, * , Huang-Chih Chang 1, 4 , Kuo-Tung Huang 1, 4 , Wen-Feng Fang 1, 3 , Yu-Mu Chen 1 , Cheng-Ta Yang 5 , Chang-Chun Hsiao 4, 6, ** , Meng-Chih Lin 1, ** , Chi-Kung Ho 2, ** and Hon-Kan Yip 6, 7, 8, 9, 10, ** 1 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan 2 Department of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan 3 Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi Campus, Chiayi, Taiwan 4 Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, Taiwan 5 Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan 6 Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 7 Division of cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 8 Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan 9 Department of Nursing, Asia University, Taichung, Taiwan 10 Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan * These authors contributed equally to this work and should be considered co-first authors ** These authors contributed equally to this work and should be considered co-correspondence authors Correspondence to: Hon-Kan Yip, email: han.gung@msa.hinet.net Keywords: advanced non-small cell lung cancer, microparticles, disease control, disease progression Received: January 09, 2017 Accepted: April 25, 2017 Published: June 06, 2017 ABSTRACT We investigated whether circulating microparticles (MPs) could serve as prognostic biomarkers in non-small cell lung cancer (NSCLC) patients. We enrolled 25 control subjects and 136 NSCLC patients categorized into disease-progression (DP, n=42) and disease-control (DC, n=94) groups. Flow cytometric analysis showed that levels of four types of circulating microparticles (EDAc-MPs, EDAp-MPs, PDAc-MPs and PDAp-MPs) were higher in the study patients than the control subjects ( P < 0.04). DP patients showed poor initially performance status and more non-adenocarcinomas than DC patients. DC patients showed more EGFR mutations and poorer performance to targeted therapy than DP patients ( P < 0.01). Three months after therapy, the levels of all four types of circulating MPs were lower in DC than DP patients ( P < 0.02), and were comparable to the levels in control subjects. In addition, the levels of circulating MPs after 3 months accurately predicted one-year prognostic outcomes ( P < 0.05). This study showed that circulating MPs are valuable prognostic biomarkers in advanced NSCLC patients.

// 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.

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.

Shih-Feng Liu,1–3 Ho-Chang Kuo,1,2,4 Guan-Heng Liu,5 Shu-Chen Ho,4 Huang-Chih Chang,1,3 Hung-Tu Huang,6 Yu-Mu Chen,1 Kuo-Tung Huang,1,3 Kuan-Yi Chen,2 Wen-Feng Fang,1–3 Meng-Chih Lin1–3 1Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, 2Department of Respiratory Therapy, Kaohsiung Chang Gung Memorial Hospital, 3Chang Gung University College of Medicine, 4Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, 5Li-Chih Valuable School, 6Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China Background: Whether the use of inhaled corticosteroids (ICSs) in patients with COPD can protect from osteoporosis remains undetermined. The aim of this study is to assess the incidence of osteoporosis in patients with COPD with ICS use and without.Patients and methods: This is a retrospective cohort and population-based study in which weextracted newly diagnosed female patients with COPD between 1997 and 2009 from Taiwan’s National Health Insurance (TNHI) database between 1996 and 2011 (International Classification of Diseases, Ninth Revision – Clinical Modification [ICD-9-CM] 491, 492, 496). The patients with COPD were defined by the presence of two or more diagnostic codes for COPD within 12months on either inpatient or outpatient service claims submitted to TNHI. Patients were excluded if they were younger than 40years or if osteoporosis had been diagnosed prior to the diagnosis of COPD and cases of asthma (ICD-9 CM code 493.X) before the index date. These enrolled patients were followed up till 2011, and the incidence of osteoporosis was determined. The Cox proportional hazards regression model was also used to estimate hazard ratios (HRs) for incidences of lung cancer.Results: Totally, 10,723 patients with COPD, including ICS users (n=812) and nonusers (n=9,911), were enrolled. The incidence rate of osteoporosis per 100,000 person years is 4,395 in nonusers and 2,709 in ICS users (HR: 0.73, 95% confidence interval [CI]: 0.63–084). The higher ICS dose is associated with lower risk of osteoporosis (0mg to ≤20mg, HR: 0.84, 95% CI: 0.69–1.04; >20mg to ≤60mg, HR: 0.78, 95% CI: 0.59–1.04; and >60mg, HR: 0.72, 95% CI: 0.55–0.96; P for trend =0.0023) after adjusting for age, income, and medications. The cumulative osteoporosis probability significantly decreased among the ICS users when compared with the nonusers (P

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.

Background Controversy exists in previous studies on macrophage M1/M2 polarization in chronic obstructive pulmonary disease (COPD). We hypothesized that formyl peptide receptor (FPR), a marker of efferocytosis and mediator of M1/M2 polarization, may be involved in the development of COPD. Methods We examined FPR 1/2/3 expressions of blood M1/M2a monocyte, neutrophil, natural killer (NK) cell, NK T cell, T helper (Th) cell, and T cytotoxic (Tc) cell by flowcytometry method in 40 patients with cigarette smoking-related COPD and 16 healthy non-smokers. Serum levels of five FPR ligands were measured by ELISA method. Results The COPD patients had lower M2a percentage and higher percentages of NK, NK T, Th, and Tc cells than the healthy non-smokers. FPR2 expressions on Th/Tc cells, FPR3 expressions of M1, M2a, NK, NK T, Th, and Tc cells, and serum annexin A1 (an endogenous FPR2 ligand) levels were all decreased in the COPD patients as compared with that in the healthy non-smokers. FPR1 expression on neutrophil was increased in the COPD patient with a high MMRC dyspnea scale, while FPR2 expression on neutrophil and annexin A1 were both decreased in the COPD patients with a history of frequent moderate exacerbation (≥ 2 events in the past 1 year). In 10 COPD patients whose blood samples were collected again after 1-year treatment, M2a percentage, FPR3 expressions of M1/NK/Th cells, FPR2 expression on Th cell, and FPR1 expression on neutrophil were all reversed to normal, in parallel with partial improvement in small airway dysfunction. Conclusions Our findings provide evidence for defective FPR2/3 and annexin A1 expressions that, associated with decreased M2a polarization, might be involved in the development of cigarette smoking induced persistent airflow limitation in COPD.

Objectives. This study aimed to identify the independent biomarkers and clinical factors that could predict ICU mortality and 6-month outcomes in relatively healthy patients with severe pneumonia and acute respiratory distress syndrome (ARDS).Patients and Methods. We prospectively enrolled patients with severe pneumonia-related ARDS that required mechanical ventilation. Patients were excluded if they were unable to take care of themselves. Several biomarkers and clinical factors were evaluated prospectively on day 1 and day 3 after ICU admission. All biomarkers and clinical factors were collected for analysis.Results. 56 patients were enrolled in this study. We determined that the initial appropriate antibiotics use was an independent clinical factor and day 1 high-mobility group protein B1 (HMGB1) concentration was an independent biomarker for ICU mortality. Interestingly, we also found that a low day 1 albumin level was an independent biomarker for predicting patient life dependence 6 months after a pneumonia event.Conclusion. Patients with severe pneumonia and ARDS requiring mechanical ventilation experience high rates of ICU mortality or disability, even if they were quite healthy before. Initial appropriate antibiotics use and day 1 level of HMGB1 were independent factors for predicting ICU mortality. Day 1 albumin level was predictive of 6-month patient life dependence.

Background. This study tested the hypothesis that circulating microparticles (MPs) are useful biomarkers for predicting one-year mortality in patients with end-stage non-small cell lung cancer (ES-NSCLC).Methods and Results. One hundred seven patients were prospectively enrolled into the study between April 2011 and February 2012, and each patient received regular follow-up after enrollment. Levels of four MPs in circulation, (1) platelet-derived activated MPs (PDAc-MPs), (2) platelet-derived apoptotic MPs (PDAp-MPs), (3) endothelial-derived activated MPs (EDAc-MPs), and (4) endothelial-derived apoptotic MPs (EDAp-MPs), were measured just after the patient was enrolled into the study using flow cytometry. Patients who survived for more than one year were categorized into group 1(n=56)(one-year survivors) and patients who survived less than one year were categorized into group 2(n=51)(one-year nonsurvivors). Male gender, incidence of liver metastasis, progression of disease after first-line treatment, poor performance status, and the Charlson comorbidity index were significantly higher in group 2 than in group 1 (allP<0.05). Additionally, as measured by flow cytometry, only the circulating level of EDAc-MPs was found to be significantly higher in group 2 than in group 1(P=0.006). Multivariate analysis demonstrated that circulating level of EDAc-MPs along with brain metastasis and male gender significantly and independently predictive of one-year mortality (allP<0.035).Conclusion. Circulating EDAc-MPs may be a useful biomarker predictive of one-year morality in ES-NSCLC patients.

Chemotherapy (CT) is the first priority treatment for advanced stage lung cancer. However, symptom distress, impaired ability to conduct daily activities, and post-CT care needs are potential side effects of CT.To explore the factors related to the care needs of post-chemotherapy lung cancer patients.A cross-sectional study was used. One hundred and twenty-one adult patients who had been diagnosed with advanced-stage lung cancer and who had undergone CT using the Platinum and Docetaxel doublet regimen were recruited from a medical center in southern Taiwan. The instruments used included a nursing care needs survey, symptoms distress scale, daily activity interference scale, and patient characteristics datasheet.Participants self-prioritized their emergency management, health consultation, and emotional support activities based on their perceived care needs. The top three post-CT symptoms in terms of severity were: fatigue, appetite change, and sleep disorder. Primary disruptions in daily activities during the post-CT period related to: holding social activities, work, and stair climbing. Significant and positive correlations were found among daily activity interference (r = .30, p.01), symptoms distress (r = .23, p.01), and care needs. The regression model indicated daily activity interference as a predictor of care needs, accounting for 10.7% of the total variance.These results highlight the relationships among care needs, symptom distress, and daily activity interference in post-chemotherapy lung-cancer patients. The present study provides a reference for nursing care to reduce the symptom distress, to enhance the performance of daily activities, and to meet the care needs of lung-cancer patients.肺癌化學治療後病人照護需求與相關因素之探討.化學治療為肺癌主要治療方式之一，然其治療期間所衍生的副作用，易造成病人的症狀困擾、日常活動干擾及照護需求。.探討肺癌病人接受化學治療後之照護需求及相關因素。.採橫斷式研究設計，取樣於南部某醫學中心121位接受Platinum和Docetaxel化學治療之肺癌病人，研究工具包括：照護需求、症狀困擾及日常活動干擾等量表。.肺癌病人化學治療後之照護需求包括：緊急問題處置、衛教及問題諮詢和情緒支持。症狀困擾嚴重度前三項依序為：疲憊、食慾不振及睡眠困擾。日常活動干擾主要項目為：保持社交活動、工作及爬樓梯。肺癌病人化學治療後日常活動干擾（r = .30, p.01）、症狀困擾（r = .23, p.01）與照護需求呈現顯著正相關。迴歸分析發現，日常活動干擾為照護需求之預測因子，可解釋之變異量為10.7%。.本研究發現，肺癌病人接受化學治療後的照護需求、症狀困擾及日常活動干擾之相關性，此結果可提供腫瘤護理人員於接受此類治療病人的護理指導參考，進而協助病人日常活動及滿足相關照護需求，以提昇病人之照護品質。.

Objectives The clinical characteristics and survival of very young (≤40 years) and very old ( > 80 years) patients with advanced non-small cell lung cancer (NSCLC) are distinct. However, the benefits of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) to patients at the extremes of age with NSCLC harboring EGFR mutation have not been well studied. We retrospectively studied the effect of extreme age on patients’ clinical characteristics and prognosis. Materials and methods Of 1510 lung cancer patients diagnosed between November 2010 and March 2014, 555 patients who were tested for EGFR mutations were included. Patients were divided into the following groups according to age: young (≤40 years), lower medium (41–60 years), higher medium (61–80 years), and very old (>80 years). Results Of the 555 patients, 20 (3.6%) patients were aged ≤40 years and 60 (10.8%) patients were aged >80 years. Young NSCLC patients had a lower BMI (p = 0.003), more brain (p = 0.016) and bone metastases (p = 0.002) Very young lung cancer patients still have poor prognosis even they were EGFR mutant. (EGFR mutant vs. wild type patients, OS: 12 vs. 7.3 months, p = 0.215) Very old NSCLC patients had a lower BMI (p = 0.003) and poor ECOG PS (p = 0.028). Positive EGFR mutation test reverses poor prognosis of elderly NSCLC patients. (EGFR mutant vs. wild type patients, OS: 13.2 vs. 4.9 months, p = 0.003) Conclusion We observed EGFR mutations reverse the poor prognosis of old patients with NSCLC. However, young patients with lung cancer have a poor prognosis even if they harbor EGFR mutations.

Lines and regimens of Intercalated chemotherapies. (DOCX 12Â kb)

Background Antacid treatments decrease the serum concentrations of first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), although it is unknown whether antacids affect clinical outcomes. As cerebrospinal fluid concentrations of TKIs are much lower than serum concentrations, we hypothesized that this drug-drug interaction might affect the prognosis of patients with de novo brain metastases. Materials and Methods This retrospective study evaluated 269 patients with EGFR-mutant non-small cell lung cancer (NSCLC) who had been diagnosed between December 2010 and December 2013, and had been treated using first-line first-generation EGFR-TKIs. Among these patients, we identified patients who concurrently used H2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) as antacids. Patients who exhibited >30% overlap between the use of TKIs and antacids were considered antacid users. Results Fifty-seven patients (57/269, 21.2%) were antacid users, and antacid use did not significantly affect progression-free survival (PFS; no antacids: 11.2 months, H2RAs: 9.4 months, PPIs: 6.7 months; p = 0.234). However, antacid use significantly reduced overall survival (OS; no antacids: 25.0 months, H2RAs: 15.5 months, PPIs: 11.3 months; p = 0.002). Antacid use did not affect PFS for various metastasis sites, although antacid users with de novo brain metastases exhibited significantly shorter OS, compared to non-users (11.8 vs. 16.3 months, respectively; p = 0.041). Antacid use did not significantly affect OS in patients with bone, liver, or pleural metastases. Conclusion Antacid use reduced OS among patients with EGFR-mutant NSCLC who were treated using first-line first-generation EGFR-TKIs, and especially among patients with de novo brain metastases.

We conducted a retrospective study of the adult patients (age ≥18 years) with serologically confirmed scrub typhus admitted between January 1998 and December 2009 at Kaohsiung Chang Gung Memorial Hospital. There were 63 adult scrub typhus patients with chest radiographic examinations. A total of 147 chest radiographs were obtained and reviewed. The most frequent abnormal findings in this study were parenchymal infiltration with bilateral and lower lung predilection. The distribution of abnormal chest radiographs was observed more than 50% during the first week. Furthermore, the progressive change was frequently observed during the first week. There is a significant correlation among laboratory findings, clinical course, and outcome. Chest radiography may be a complementary tool to evaluate the clinical course of scrub typhus and chest radiographic examinations should be taken during the first week after the onset of illness.