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It has been demonstrated that the traditional Chinese medicine rikkunshito, ameliorates anorexia in several types of human cancer and attenuates lung injury by inhibiting neutrophil infiltration. The current study investigated the clinical and hematological effects of rikkunshito and its underlying mechanisms of action in the treatment of advanced non-small cell lung cancer (NSCLC). The Illumina microarray BeadChip was used to analyze the whole-genome expression profiles of peripheral blood mononuclear cells in 17 patients with advanced NSCLC. These patients were randomized to receive combination chemotherapy (cisplatin and gemcitabine) with (n=9, CTH+R group) or without (n=8, CTH group) rikkunshito. The primary endpoint was the treatment response and the categories of the scales of anorexia, nausea, vomiting and fatigue; secondary endpoints included the hematological effect and whole genome gene expression changes. The results of the current study indicated that there were no significant differences in clinical outcomes, including treatment response and toxicity events, between the two groups. Median one-year overall survival (OS) was 12 months in the CTH group and 11 months in the CTH+R group (P=0.058 by log-rank test), while old age (>60 years old) was the only independent factor associated with one-year OS (hazard ratio 1.095, 95% confidence interval, 1.09-1.189, P=0.030). Patients in the CTH+R group experienced significantly greater maximum decreases in both white cell count (P=0.034) and absolute neutrophil count (P=0.030) from the baseline. A total of 111 genes associated with neutrophil apoptosis, the cell-killing ability of neutrophils, natural killer cell activation and B cell proliferation were up-regulated following rikkunshito treatment. A total of 48 genes associated with neutrophil migration, coagulation, thrombosis and type I interferon signaling were down-regulated following rikkunshito treatment. Rikkunshito may therefore affect the blood neutrophil count when used with combination chemotherapy in patients with NSCLC, potentially by down-regulating prostaglandin-endoperoxidase synthase 1, MPL, AMICA1 and junctional adhesion molecule 3, while up-regulating elastase, neutrophil expressed, proteinase 3, cathepsin G and cluster of differentiation 24.

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.

Nai-Ying Kuo,1,2 Mei-Lien Tu,1,3 Tsai-Yi Hung,1 Shih-Feng Liu,4 Yu-Hsiu Chung,4 Meng-Chih Lin,4 Chao-Chien Wu41Department of Respiratory Therapy, Kaohsiung Chang Gung Memorial Hospital; 2Kaohsiung Medical University; 3Respiratory Care, Chang Gung University of Science and Technology, Chiayi, Taiwan; 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, TaiwanBackground: Patient-ventilator asynchrony is a common problem in mechanically ventilated patients; the problem is especially obvious in COPD. Neutrally adjusted ventilatory assist (NAVA) can improve patient-ventilator asynchrony; however, the effect in COPD patients with prolonged mechanical ventilation is still unknown. The goals of this study are to evaluate the effect of NAVA and conventional weaning mode in patients with COPD during prolonged mechanical ventilation.Methods: The study enrolled a total of 33 COPD patients with ventilator dependency for more than 21 days in the weaning center. A diaphragm electrical activity (Edi) catheter was inserted in patients within 24 hours after admission to the respiratory care center, and patients were randomly allocated to NAVA or conventional group. A spontaneous breathing trial was performed every 24 hours. The results correlated with the clinical parameters.Results: There were significantly higher asynchrony incidence rates in the whole group after using Edi catheter (before vs post-Edi catheter insertion =60.6% vs 87.9%, P

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.

Background The prompt initial use of appropriate antibiotics should improve mortality rates in adults with ventilator-associated pneumonia (VAP). However, the incidence of multidrug-resistant (MDR) pathogen infections is on the rise, and the choice of the initial empiric antibiotic may be challenging. We investigated whether appropriate initial antibiotic therapy, infective pathogens, and the clinical severity index influence hospital mortality in patients with VAP and determined independent risk factors for the same. Methods This study evaluated 163 adult patients (aged ≥ 18 years) at Chang Gung Memorial Hospital, Kaohsiung, Taiwan, from January 1, 2007, to January 31, 2008. Eligibility was evaluated based on criteria for VAP. Sequential Organ Failure Assessment (SOFA) scores, Acute Physiological Assessment and Chronic Health Evaluation II (APACHE II) scores, oxygenation index, underlying comorbidities, septic shock status, previous tracheostomy status, and factors related to pneumonia were collected for analysis. Results Ninety-two patients survived from a total 163 patients with VAP during the course of their confinement in the intensive care unit. Multivariable logistic regression analysis identified that a pre-existing Charlson Comorbidity Index score ( P = .011), initial oxygenation index ( P = .025), SOFA score ( P = .043), VAP caused by Acinetobacter baumanii ( P = .030), and infection with MDR pathogens ( P = .003) were independent risk factors for hospital mortality in patients with VAP. Conclusion High Charlson Comorbidity Index score, high initial oxygenation index, high SOFA score, and infection with Acinetobacter baumannii or MDR pathogens significantly affect hospital mortality in patients with VAP.

Background/PurposeVentilator-associated pneumonia (VAP) caused by Acinetobacter baumannii has contributed to high mortality rate, prolonged stays in the intensive care unit, and the rapid development of antimicrobial resistance to commonly used antimicrobials. This study sought to determine predictors of mortality and carbapenem resistance for patients with A baumannii VAP.MethodsWe retrospectively reviewed 541 adult patients with A baumannii pneumonia, who were admitted to a medical center between 2005 and 2007; of which 180 (33.3%) had been treated with mechanical ventilation. Of the 180 patients, 98 (54.4%) who survived were categorized as the survivor group, and 82 (45.6%) who died as the mortality group. Eighty-seven (48.3%) with imipenem-sensitive A baumannii VAP were categorized as the IS-AB group, and the remaining 93 (51.7%) with imipenem-resistant VAP as the IR-AB group.ResultsCompared with the survivor group, the mortality group had significantly higher Charlson comorbidity index scores, and more neoplastic disease, other sites of infection, bloodstream infections, altered mental status, confusion, urea >7 mmol/L, respiratory rate >30/min, low blood pressure (systolic 65 years (CURB-65) ≥ 3, creatinine > 1.6 mg/dL, C-reactive protein ≥ 100 mg/L, and imipenem resistance. The survivor group had more cases of tracheostomy and diabetes mellitus than the mortality group had. Compared with the IS-AB group, the IR-AB group had higher Charlson comorbidity index scores, longer stays before VAP onset, an increase in other sites of infection, white blood cell count 1.1 × 104/μL, and higher hospital mortality rates.ConclusionInadequate initial empiric antimicrobial therapy and higher disease severity scores, including CURB ≥ 3 and C-reactive protein ≥ 120 mg/L, were independent risk factors associated with higher mortality rates for A baumannii pneumonia. Length of stay before VAP and white blood cell count 1.1 × 104/μL were independent risk factors for carbapenem resistance.

Background The diagnostic yield of endobronchial ultrasonography-guided transbronchial needle aspiration (TBNA) for peripheral pulmonary lesions (PPLs) has not been evaluated. The diagnostic impact of TBNA when the EBUS probe is adjacent to lesions remains to be determined. Design A prospective, randomized trial. Methods Two hundred two patients with PPLs and positive EBUS findings were enrolled. They were randomly classified into two groups. In the EBUS conventional diagnostic procedures (CDPs) group (103 patients), both transbronchial biopsy (TBB) and bronchial washing (BW) were performed. In the EBUS-TBNA plus CDPs group (99 patients), TBNA, TBB, and BW were performed. The diagnostic yield in each group was compared. Results A total of 182 patients (94 in the EBUS CDPs group and 88 in the EBUS-TBNA plus CDPs group) were analyzed. The yield in the EBUS-TBNA plus CDPs group (78.4%) was significantly higher than the EBUS CDPs group (60.6%, p = 0.015). Cases in which the EBUS probe was located within the lesions had a significantly higher diagnostic yield (78.3%) than when the EBUS probe was adjacent to them (47.2%, p Conclusions Applying TBNA to EBUS-guided CDPs further increased the diagnostic yield of PPLs without additional risk. The diagnostic advantage of TBNA became more obvious if the EBUS probe was adjacent to the lesions. Trial registration Clinicaltrials.gov Identifier: NCT00626587.

Endobronchial ultrasonography (EBUS) rapidly and accurately localizes peripheral pulmonary lesions. It can aid differential diagnosis by characterizing lesions and discriminating between neoplastic and non-neoplastic disease. From July 2005 through December 2006, patients with peripheral lesions underwent EBUS examination in a tertiary-referral teaching hospital. Image characteristics were subsequently correlated with definite histopathologic diagnosis. Three current-issued image patterns of EBUS were assayed from 40 initial patients, including (a) hypoechoic areas, (b) anechoic areas and (c) luminant areas around the probe. Excluding 22 cases because of inconsistent typing, 193 patients possessing definite diagnoses were enrolled in the investigation, of which 107 cases (55.4%) were neoplastic diseases. Hypoechoic areas appeared to be unrelated to the nature of the lesions (p = 0.288). Most lesions with anechoic areas were neoplasms (18 of 21 cases, 85.7%) and lesions without luminant areas suggested non-neoplastic disease (19 of 24 cases, 79.2%). Anechoic and luminant areas were significantly different between neoplasm and non-neoplasm groups (p = 0.003 and p < 0.001, respectively). The average additional time for EBUS required was 3.85 +/- 2.36 min (range 1 to 13 min). In conclusion, this uncomplicated and time-saving method of using EBUS image patterns could provide additional information to facilitate differential diagnoses.

There has been no previously reported case series study regarding chest radiographic (CXR) presentations in dengue hemorrhagic fever (DHF) patients. We retrospectively studied 363 DHF patients from June to December 2002 in southern Taiwan, and a total of 468 CXRs were obtained and reviewed. More than 50% of these showed abnormalities after the 3rd day, with infiltration only and small pleural effusion as the major findings. Progressive changes during the first week and improvements during the second week were observed in these abnormal CXRs. The CXR presentation was also significantly correlated with laboratory findings (white blood cell count, platelet levels, activated partial thromboplastin time, and alanine aminotransferase and albumin levels), as well as the clinical course (renal insufficiency, liver function impairment, upper gastrointestinal bleeding, combination bacterial infection, and duration of admission) and outcome (mortality). The CXR may therefore be a modality for evaluating the clinical course of DHF and should be made during first week after the onset of illness.

To investigate clinical course and outcome of dengue with acute respiratory failure (ARF), and to identify related risk factors for acquiring ARF in dengue, we retrospectively studied 11 dengue patients with ARF. From June to December 2002, a total of 606 adult patients were diagnosed as having dengue. Eleven (1.8%) of 606 dengue patients had complications of ARF. The main causes of ARF were sepsis (n = 6, 54.5%) and upper gastrointestinal (UGI) bleeding (n = 3, 27.3%). The mortality rate was 72.7% (n = 8). Additionally, univariate analysis showed that age, dyspnea, cough, prothrombin time, activated partial thromboplastin time, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, creatinine, albumin, renal insufficiency, acute renal failure, acute hepatic failure, UGI bleeding, and combination bacterial infection were significantly predictive variables associated with dengue patients with ARF.

Background Patients with early-stage lung cancer who have a high baseline lymphocyte-to-monocyte ratio (LMR) have a favorable prognosis. However, the prognostic significance of LMR in patients with advanced-stage EGFR-mutant non-small cell lung cancer (NSCLC) receiving first-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) has not been established. We conducted a retrospective analysis to investigate the influence of LMR on clinical outcomes including progression-free survival (PFS) and overall survival (OS) in EGFR-mutant patients with NSCLC. Materials and Methods Of 1310 lung cancer patients diagnosed between January 2011 and October 2013, 253 patients receiving first-line EGFR-TKIs for EGFR-mutant NSCLC were included. The cut-off values for baseline and the 1-month-to-baseline ratio of LMR (MBR), determined by using receiver operating characteristic curves, were 3.29 and 0.63, respectively. Patients were divided into 3 prognostic groups: high LMR and MBR, high LMR or MBR, and low LMR and MBR. Results The mean patient age was 65.2 years, and 41% were men. The median PFS and OS were 10.3 and 22.0 months, respectively. The PFS in patients with high LMR and MBR, high LMR or MBR, and low LMR and MBR were 15.4, 7.1, and 2.0 months, respectively (p < 0.001), whereas the OS were 32.6, 13.7, and 5.1 months, respectively (p < 0.001). Conclusion A combination of baseline and trend of LMR can be used to identify patients with a high mortality risk in EGFR-mutant NSCLC patients receiving first-line EGFR-TKIs.

To attempt to develop a simple method to discriminate between neoplasm and nonneoplasm peripheral pulmonary lesions based on images of endobronchial ultrasonography (EBUS).Between June 2004 and June 2005, 151 patients with bronchoscopic peripheral lesions that could not be detected via a conventional bronchoscope underwent EBUS for advanced localization with a 20-MHz miniature radial probe in a tertiary-referral teaching hospital. The image characteristics were applied subsequently to correlate definite histopathologic results in studied patients.Based on an initial 20 consecutive patients with a definite diagnosis, four image characteristics were issued: (1) continuous hyperechoic margin outside the lesion, (2) homogeneous, or heterogeneous internal echoes, (3) hyperechoic dots in the lesion, and (4) concentric circles along the echo probe. In the following 131 patients, excluding five cases due to inconsistent typing, 93 patients (73.8%) established a diagnosis later. Most cases involving the image characteristics of homogenous internal echoes and concentric circles had nonneoplasm lesions (18 of 19 cases, 94.7%, and 14 of 16 cases, 87.5%, respectively). The difference shown in these two respects with neoplasm lesions was significant by univariate analysis (p0.001), although only concentric circles had a significant p value after multivariate analysis. Another two image patterns (continuous hyperechoic margins and hyperechoic dots) did not yield a significant difference (p = 0.090 and p = 0.079, respectively). The average additional time for EBUS was 3.94 min (1.5 to 10 min).EBUS can provide characteristic information to differentiate the nature of a peripheral pulmonary lesion from the image characteristics of concentric circles.

In the pre-tyrosine kinase inhibitors (TKIs) era, non-small cell lung cancer (NSCLC) patients with de novo bone metastases had a worse prognosis than those without. However, whether epidermal growth factor receptor (EGFR)-TKIs affect the outcomes of EGFR mutant NSCLC patients with de novo bone metastases has not been well studied thus far. We retrospectively studied the effect of EGFR mutation status and first-line EGFR-TKIs on patient outcomes and created a survival scoring system for NSCLC patients with de novo bone metastases. This retrospective study evaluated 1510 NSCLC patients diagnosed between November 2010 and March 2014. Among these patients, 234 patients had de novo bone metastases. We found that 121 of these 234 patients (51.7%) had positive EGFR mutation tests, and a positive EGFR mutation test significantly affected overall survival (OS) (EGFR mutant: 15.2 months, EGFR wild type: 6.5 months; p < 0.001). Other prognostic factors significant in the multivariable analysis for NSCLC with de novo bone metastases included Eastern Cooperative Oncology Group performance status (PS) (OS; PS 0–2: 11.2 months, PS 3–4: 4.9 months; p = 0.002), presence of extraosseous metastases (OS; with extraosseous metastases: 8.8 months, without extraosseous metastases: 14.0 months; p = 0.008), blood lymphocyte-to-monocyte ratio (LMR) (OS; LMR > 3.1: 17.1months, LMR ≤ 3.1: 6.9months; p < 0.001). A positive EGFR mutation status reversed the poor outcomes of NSCLC patients with de novo bone metastases. A simple and useful survival scoring system including the above clinical parameters was thus created for NSCLC patients with de novo bone metastases.

Primary pulmonary melanoma is a rare disease, and only 20 cases have been published previously in the English literature. A 44-year-old woman presented initially with haemoptysis, and a chest roentgenogram showed a single lung mass. The diagnosis of primary pulmonary melanoma necessitates reliance on both clinical and histological criteria. The image of endobronchial ultrasonography (EBUS) in our case was not distinct from the image of lung cancer.

Objectives. To determine risk factors associated with ventilator dependence in patients with ventilator-associated pneumonia (VAP).Study Design. A retrospective study was conducted at Chang Gung Memorial Hospital, Kaohsiung, from January 1, 2007 to January 31, 2008.Methods. This study evaluated 163 adult patients (aged ≥18 years). Eligibility was evaluated according to the criterion for VAP, Sequential Organ Failure Assessment (SOFA) score, Acute Physiological Assessment and Chronic Health Evaluation II (APACHE II) score. Oxygenation index, underlying comorbidities, septic shock status, previous tracheostomy status, and factors related to pneumonia were collected for analysis.Results. Of the 163 VAP patients in the study, 90 patients survived, yielding a mortality rate of 44.8%. Among the 90 surviving patients, only 36 (40%) had been weaned off ventilators at the time of discharge. Multivariate logistic regression analysis was used to identify underlying factors such as congestive cardiac failure (P=0.009), initial high oxygenation index value (P=0.04), increased SOFA scores (P=0.01), and increased APACHE II scores (P=0.02) as independent predictors of ventilator dependence. Results from the Kaplan-Meier method indicate that initial therapy with antibiotics could increase the ventilator weaning rate (log Rank test,P<0.001).Conclusions. Preexisting cardiopulmonary function, high APACHE II and SOFA scores, and high oxygenation index were the strongest predictors of ventilator dependence. Initial empiric antibiotic treatment can improve ventilator weaning rates at the time of discharge.

Among epidermal growth factor receptor (EGFR) mutation status unknown nonsmall cell lung cancer (NSCLC) patients, those with higher carcinoembryonic antigen (CEA) level are more likely to response to EGFR-tyrosine kinase inhibitors (TKIs) because they tend to have mutant epidermal growth factor receptor (EGFR). However, patients with higher CEA also have more tumor burden. With the above paradoxical evidence, it is prudent to understand the prognostic significance of baseline CEA in patients with EGFR-mutant NSCLC treated with first-line EGFR-TKIs. The clinical significance of the trend in CEA after treatment and the impact of CEA normalization during EGFR-TKI therapy are also unknown and potentially important. A total of 241 patients who received first-line EGFR-TKIs were included. As to baseline CEA, patients were divided into normal, low, and high baseline CEA by cut point determined by receiver operating characteristic curves. As to CEA responses, patients were divided into 3 groups accordingly to their amount of CEA change after taking TKIs. In group A, 1-month follow-up CEA level decreased more than 35% with nadir CEA normalization; in group B, 1-month follow-up CEA level decreased more than 35% without nadir CEA normalization; and in group C, 1-month follow-up CEA level decreased less than 35% or increased. Patients with higher baseline CEA levels had shorter progression-free survival (PFS) and overall survival (OS) (CEA > 32 vs 5–32 vs

A skewed T-helper (T(h))1/T(h)2 immune response is considered to be the major cause of allergic disorders. Overproduction of T(h)2 cytokines, which promote recruitment and activation of mast cells and eosinophils, plays a key part in the pathogenesis of allergic asthma. The mechanisms by which omalizumab is effective in asthma treatment are not yet fully understood. A 16-year-old girl who was experiencing frequent asthma attacks in spite of daily administration of budesonide (640 μg) and montelukast (10mg) was given omalizumab (375 mg) at intervals of 2 weeks, to prevent a visit to the emergency room. Plasma levels of T(h)1 cytokines [interferon (IFN)-γ and interleukin (IL)-12p70], T(h)2 cytokines (IL-4 and IL-13), other proinflammatory and regulatory cytokines [IL-6, IL-10, IL-17, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β], chemokines [monocyte chemotactic protein (MCP)-1, chemokine ligand (CCL)7, and CCL17], and soluble Fas ligand (sFasL) were measured before treatment and after treatment for 8 weeks. She showed a good clinical response to omalizumab: her lung function parameters improved and the use of β2-agonist decreased. No emergency room visits were required after omalizumab treatment for 8 weeks. Plasma levels of sFasL and TGF-β showed obvious increases after omalizumab therapy. IL-12p70 levels were decreased as compared to the corresponding baseline levels. These findings suggest that the effects of omalizumab in asthma treatment are not restricted to the regulation of the skewed T(h)1/T(h)2 cytokine immune response, and sFasL-mediated apoptosis and regulatory T-cell (Treg)-mediated TGF-β seem to have important roles in the therapeutic effects of omalizumab.

Gefitinib is effective in treating patients with non–small-cell lung cancer (NSCLC). The response rate and improvement in survival are related to several aspects, including race, gender, smoking status, and histology; however, little is known about the relationship between survival and length of gefitinib treatment. We conducted this retrospective study to examine this relationship and identify the predictive factors influencing survival and tumor response in chemonaive and chemotherapy patients who had stage IIIb or IV NSCLC with unknown epidermal growth factor receptor mutants. This analysis was aimed to clarify the difference between first- and second-line gefitinib therapy. Among the 918 newly diagnosed, inoperable NSCLC patients from March 2003 to December 2006, 437 (47.6%) had ever received gefitinib therapy. One hundred forty-nine patients (34.0%) who selected gefitinib as first- or second-line therapy were included in the analysis. The overall survival rates of first- and second-line gefitinib therapy were 12.8 months and 20.7 months, respectively ( P = .110). The shorter overall survival may be caused by the omission of platinum-based doublet chemotherapy in 37 patients from the first-line group (39.4%). There was also no significant difference in progression-free survival (6.8 months versus 4.9 months; P = .415), and the objective tumor response and disease control rates were similar. Better prognosis and tumor response was associated with female gender, adenocarcinoma, nonsmokers, and good performance status. The difference in overall survival between patients undergoing second-line treatment compared with those undergoing first-line treatment preceding chemotherapy was significant ( P = .041). The overall survival, progression-free survival, and tumor response rates were similar in the patients who received gefitinib as initial therapy or after conventional chemotherapy.

The aim of this study was to investigate genetic effects on the pathogenesis of chronic obstructive pulmonary disease (COPD). The study was conducted as a prospective case-control study in a medical center in southern Taiwan. The patient group consisted of 145 male patients with smoking-related COPD and a control group of 139 resistant smokers from July 2004 to September 2009. We compared allele and genotype frequencies of three tag single nucleotide polymorphisms (SNP) of the TNF-alpha gene promoter region at -308, -863, and -1031 in all subjects. We also analyzed the influence of each genetic variant on pulmonary function parameters, body mass index (BMI), serum TNF-alpha levels, and outcomes among heavy smokers with or without COPD. COPD patients had a significantly lower A allele frequency (9.7 vs. 15.1%, OR = 0.6, p = 0.048, false discovery rate q = 0.144) and a significantly lower A carrier genotype frequency (19.3 vs. 30.2%, OR = 0.52, p = 0.042, q = 0.135) than resistant smokers. The -863 CA genotype was associated with a better FEV(1)/FVC ratio (79 vs. 71.5%, p = 0.034), and higher BMI (24.9 vs. 23.6 kg/m(2), p = 0.048). In addition, COPD patients with the -1031 C carrier genotype had higher serum TNF-alpha levels (20.9 vs. 16.2 pg/ml, p = 0.01). BMI (hazard ratio = 0.84, 95% CI = 0.74-0.96, p = 0.008) was the only independent predictor for mortality. The TNF-alpha -863 A allele may confer a degree of resistance to the susceptibility to and muscle wasting of COPD among heavy smokers.

The diagnostic yield of endobronchial ultrasonography (EBUS)-guided transbronchial needle aspiration (TBNA) for peripheral pulmonary lesions (PPLs) has not been evaluated. The diagnostic impact of TBNA when the EBUS probe is adjacent to lesions remains to be determined.A prospective, randomized trial.Two hundred two patients with PPLs and positive EBUS findings were enrolled. They were randomly classified into two groups. In the EBUS conventional diagnostic procedures (CDPs) group (103 patients), both transbronchial biopsy (TBB) and bronchial washing (BW) were performed. In the EBUS-TBNA plus CDPs group (99 patients), TBNA, TBB, and BW were performed. The diagnostic yield in each group was compared.A total of 182 patients (94 in the EBUS CDPs group and 88 in the EBUS-TBNA plus CDPs group) were analyzed. The yield in the EBUS-TBNA plus CDPs group (78.4%) was significantly higher than the EBUS CDPs group (60.6%, p = 0.015). Cases in which the EBUS probe was located within the lesions had a significantly higher diagnostic yield (78.3%) than when the EBUS probe was adjacent to them (47.2%, p0.001). Concerning the three different techniques, TBNA showed the highest diagnostic yield (62.5%) in comparison to TBB (48.9%) and to BW (19.8%). The diagnostic yield of TBNA remained unchanged even when the EBUS probe was adjacent to the lesions (p = 0.89). No additional adverse effects were observed in the EBUS-TBNA plus CDPs group.Applying TBNA to EBUS-guided CDPs further increased the diagnostic yield of PPLs without additional risk. The diagnostic advantage of TBNA became more obvious if the EBUS probe was adjacent to the lesions.Clinicaltrials.gov Identifier: NCT00626587.

Scrub typhus is a mite-borne infectious disease caused by Orientia tsutsugamushi. Acute respiratory distress syndrome (ARDS) is a serious complication of scrub typhus. This study retrospectively reviewed the medical records of 72 patients diagnosed with scrub typhus from January 1998 to August 2006 in Kaohsiung Chang Gung Memorial Hospital in Taiwan. Eight of 72 scrub typhus patients with ARDS were included in the study; the other patients without ARDS were used as controls. The mortality rate for the scrub typhus patients with ARDS was 25%. The eight patients seldom had underlying diseases. Initial presentations of dyspnea and cough, white blood cell count, hematocrit, total bilirubin, and delayed used of appropriate antibiotics use were significant predictors of ARDS. Multivariate analysis showed that albumin, prothrombin time, and delayed use of appropriate antibiotics were independent predictors of ARDS. Identification of these relative risk factors may help clinicians evaluate clinical cases of scrub typhus with ARDS.

Oxygen desaturation is not uncommon during bronchoscopy. We sought to identify factors predictive of desaturation during flexible bronchoscopy.Over eight months, we enrolled 137 randomly selected patients who were undergoing fiberoptic bronchoscopy at our medical center. The patients' oxygen saturation was monitored on their arrival and during the procedure by finger pulse oximetry. Desaturation was defined as an overall saturation nadir of90% or an episode of decreased saturation of 5% from the baseline regardless of whether the patient was receiving supplemental oxygen.The need for oxygen supplementation before the procedure was predictive of a higher rate of desaturation episodes (73.9% vs. 50%, p = 0.036). Although all interventional procedures or their complications can cause desaturation, the specific type of procedure was the most important predictor of desaturation (lavage, 88.9%; washing, 43.8%; brushing, 15.2%; biopsy, 10%). A low peak expiratory flow rate before the procedure seemed to be predictive of a high desaturation rate in patients undergoing lavage or washing during bronchoscopy.Our study suggested that age, sex and baseline oxygen saturation were not predictors of desaturation. We should be reminded of the possibility of desaturation during every procedure, especially in patients who need supplemental oxygen before bronchoscopy.

Summary Background We assessed the effectiveness of applying the distance from the orifice of the bronchus to visualized peripheral pulmonary lesion (PPL) under endobronchial ultrasonography (EBUS) to transbronchial biopsy (TBB), as an alternative to EBUS with a guide sheath (GS) and fluoroscopy. Patients and methods From October 2004 to July 2005, a total of 158 consecutive patients with solitary PPLs, which were not visualized under flexible video bronchoscopy, were received EBUS for advanced localization subsequently. One hundred and thirteen of 158 patients with solitary PPLs which were visualized on EBUS image were included in this prospective study and randomly divided into two groups for TBB using different methods. In group EBUS-D (57 patients) the distance from the bronchial orifice to pulmonary lesion was measured, then the biopsy forceps were advanced to this measured distance and biopsy followed. In group EBUS (56 patients) the biopsy forceps were advanced regardless of distance. The diagnostic yields were then compared. Results TBBs in group EBUS-D patients had a significantly higher diagnostic yield (45/57, 78.9%) than group EBUS patients (32/56, 57.1%) [ P = 0.013 ]. Size and location of lesion, duration of EBUS, diagnosis of malignancy, and whether the probe was located within the lesion on EBUS image did not differ between these two groups. Mild bleeding occurred in three patients in group EBUS-D and two in group EBUS. One group EBUS patient had a self-limited pneumothorax. Conclusions Measuring and applying the distance between the orifice of bronchus and the lesion could increase the diagnostic yield of EBUS-guided TBBs for PPLs.

An epithelial-myoepithelial tumor is an extremely rare pulmonary neoplasm. Only 21 cases have been reported to date. This report presents a case of left main bronchial epithelial-myoepithelial carcinoma in a 43-year-old woman. No mediastinal lymph nodes were enlarged in computed tomographic scan, and no tumor growth was noted beyond the bronchial cartilage layer by endobronchial ultrasound imaging. This report highlights the usefulness of endobronchial ultrasound imaging for determining the depth of tumor invasion and choosing an alternative approach to surgical resection.

This is a prospective study of peri-procedure and post-procedure complications and successful weaning of long-term mechanically-ventilated patients following video bronchoscopy-guided percutaneous dilatational tracheostomy (PDT).Video bronchoscopy guided PDT was performed for long-term mechanically-ventilated patients in a medical intensive care unit (ICU). Peri-procedure and post-procedure complications were prospectively observed and evaluated. The success of weaning and the factors affecting the outcomes of these patients after PDT were also investigated.A total of 107 patients with mechanical ventilation were enrolled. The average duration of trans-laryngeal intubation was 27.8 +/- 18.4 days which was longer than reported in previous studies. There were 70 men and 37 women, all of whom underwent bedside PDT at a medical ICU. The complication rates during and post-procedure were 8.4% and 14%, respectively. The most common complications were desaturation during the procedure and bleeding during the follow-up period. Only one death was procedure related (0.9%). After PDT, 50 patients (46.7%) were successfully weaned from mechanical ventilation. The rate of successful weaning (p = 0.02) increased while the days to achievement (p0.001) decreased with decreasing duration of trans-laryngeal intubation. Gender, age, body weight, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, duration of procedure, endotracheal tube diameter and position, and history of self-extubation were not related to successful weaning.PDT is a bedside procedure with relatively low complication and mortality rates when performed for patients on long-term mechanical ventilation in a medical ICU. The previous duration of trans-laryngeal intubation was an important determinant for successful weaning after PDT.

The cuff-leak test has been proposed as a simple tool to clinically predict stridor or respiratory distress secondary to laryngeal edema following extubation. However, the true incidence of laryngeal edema in patients on long-term mechanical ventilation is uncertain. The relationship between upper airway obstruction (detected by video bronchoscopy) and the cuff-leak test value for patients with prolonged translaryngeal intubation during percutaneous dilatational tracheostomy (PDT) was investigated.Prospective, clinical investigation.Intensive care unit of a university hospital.Ninety-five patients with prolonged translaryngeal intubation requiring PDT were enrolled during a 12-month period.Cuff-leak test, PDT, video bronchoscopy.The average duration of translaryngeal intubation was 28.1 +/- 17.6 days. The incidence of severe laryngeal edema was 36.8% (35/95). We chose 140 mL as the threshold cuff-leak volume below which edema is indicated. The rate of cuff-leak test positivity was 38.9% (37/95). The sensitivity and the specificity of the test were 88.6% and 90.0%, respectively. The positive and negative predictive values were 83.8% and 93.1%, respectively. Patients who developed severe laryngeal edema had a smaller leak volume than those who did not, expressed in absolute values (53.9 +/- 56.2 vs. 287.9 +/- 120.0 mL; p.001) or in relative values (10.1 +/- 10.2 vs. 55.3 +/- 22.7%, p.001). The occurrence of severe laryngeal edema was not associated with age, gender, body weight, respiratory failure due to pneumonia, duration of translaryngeal intubation, endotracheal tube diameter, Acute Physiology and Chronic Health Evaluation II score, or history of self-extubation.A reduced cuff-leak volume measured before PDT may signal the presence of severe laryngeal edema in patients on long-term mechanical ventilation.

Background: Persistent impaired pulmonary function and functional capacity are common among survivors of severe acute respiratory syndrome (SARS). Whether the impairment was caused by SARS or pre-existing physical condition remains unclear. Objective: This study investigated the influence of SARS on exercise capacity and pulmonary function of previously healthy medical staff.Methods: Pulmonary function tests, including spirometry and carbon monoxide diffusing capacity (DLCO), as well as symptom-limited cardiopulmonary exercise testing (CPET) with an incremental protocol using an electronically braked cycle ergometer, were performed by 13 previously healthy hospital workers 14 months after SARS recovery. Other 14 age- and sex-matched healthy medical workers completed CPET simultaneously, and exercise capacities of these two groups were compared. Results: Most values of spirometry performed were within normal range. Only one showed mildly restrictive abnormality with decreased forced expiratory volume in 1 s (72.2% predicted) and forced vital capacity (68.1% predicted). Eight subjects had decreased DLCO levels (mean 79.37 ± 7.73%), and low exercise capacity was noted in 9 subjects. Discordance in impairment of the measured DLCO and exercise capacity was revealed by comparison. Besides, there was no significant difference in results of CPET between subjects recovered from SARS and those never infected. Conclusions: Minor pulmonary function defects as well as decreased exercise capacity were detected in previously healthy medical staff after recovering from SARS. No significant correlation between exercise capacity and pulmonary function was found.

There are many strategies available to treat palliation of airway obstruction due to benign or malignant conditions. The initial choice depends on the urgency of the situation, the extent of the disease process as assessed bronchoscopically, as well as the individual experience and preference of the physician. We present a rare case of complete tracheal transection following a traffic accident. Respiratory distress, which resulted from post-anastomotic tracheal stricture, developed progressively about 2 months after surgical repair. Symptomatic relief and improved ventilatory function were achieved in this patient once patency of the trachea was restored successfully using bronchoscopic electrocautery. The technique is a straightforward, safe, and quick method to palliate airway obstruction.

AIM: To identify risk factors predictive of intensive care unit (ICU) mortality in patients with ventilator-related pancreatitis. The clinical outcomes of patients with ventilator-related pancreatitis were compared with those of patients with pancreatitis-related respiratory failure as well as controls. METHODS: One hundred and forty-eight patients with respiratory failure requiring mechanical ventilation and concomitant acute pancreatitis were identified from a prospectively collected dataset of 9108 consecutive patients admitted with respiratory failure over a period of five years. Sixty patients met the criteria for ventilator-related pancreatitis, and 88 (control patients), for pancreatitis-related respiratory failure. RESULTS: Mortality rate in ventilator-related pancreatitis was comparable to that in ICU patients without pancreatitis by case-control methodology (P = 0.544). Multivariate logistic regression analysis identified low PaO2/FiO2 (OR: 1.032, 95% CI: 1.006-1.059, P = 0.016) as an independent risk factor for mortality in patients with ventilator-related pancreatitis. The mortality rate in patients with ventilator-related pancreatitis was lower than that in patients with acute pancreatitis-related respiratory failure (P < 0.001). CONCLUSION: We found that low PaO2/FiO2 was an independent clinical parameter predictive of ICU mortality in patients with ventilator-related pancreatitis.