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Introduction: Endothelial cell (EC) activation may increase systemic vascular permeability caused an extravasation of water (EVLW) in sepsis with acute respiratory distress syndrome (ARDS). The correlation of thrombin and EVLW in sepsis and ARDS hasn’t addressed.Methods Septic patients with ARDS were prospectively enrolled during 2014 and 2016, and EVLW and serum thrombin on day 1 and 3 were measured and compared between those with survival and non-survival. Additionally, morphologic change of human umbilical vein endothelial cells (HUVECs) with serum from patients with high and low EVLW was conducted.Results Twenty-seven patients were enrolled and the baseline characters including age, gender, APACHE II, prior 24hrs fluid balance, BMI, and shock status were similar between survivors and non-survivors. But day 1 EVLW was higher in non-survivor (27.5 ± 8.4 vs. 22 ± 6.5 ml/kg, p = 0.049). EVLW of survivor was improved from day 1 to day 3 (22 ± 6.5 vs. 11 ± 3.8 ml/kg, p = 0.0001), but it did not improve in non-survivor (27.5 ± 8.4 vs. 28 ± 6.7 ml/kg, p = 0.89). Thrombin level of survivor significantly improved (1.03 ± 0.55 vs. 0.87 ± 0.25 U/ml, p = 0.04) but it did not improve in non-survivor (1.97 ± 0.75 vs. 2.2 ± 0.75 U/ml, p = 0.07) from day 1 to day 3. EVLW and thrombin revealed a positive correlation (r2 = 0.71, p Conclusion The level of EVLW and thrombin correlated positively and may impact the survival of these patients. Thrombin inhibitor may act as a novel valuable approach for preventing endothelial hyper-permeability and provides the rational basis for the use of this kind of drug in patients with severe sepsis and ARDS.

Introduction The clinical features of patients with metastatic epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma receiving first-line therapy based on erlotinib combined with bevacizumab are unclear. Here, we sought to analyze the clinical features of this patient group. Methods Data were analyzed for the period from January 2015 to August 2019 for 49 patients with metastatic EGFR-mutated lung adenocarcinoma receiving first-line erlotinib-and-bevacizumab combination therapy from the Linkou and Kaohsiung Chang Gung Memorial Hospitals. Results The combination of erlotinib and bevacizumab showed an 83.7% objective response rate and a 97.9% disease control rate. The median progression-free survival (PFS) and overall survival (OS) were 22.0 [95% CI (19.7–22.33)] and 47.6 [95% CI (38.87–56.37)] months, respectively, for all patients. The secondary EGFR-T790M mutation rate in the patients with acquired resistance to the combination was 72.4%. No predictive factor associated with the appearance of secondary EGFR-T790M mutations was found. The most frequent adverse event (AE) caused by the combination therapy was dermatitis (100%), and most of the AEs were manageable and grades 1 and 2. Conclusion Erlotinib combined with bevacizumab is an effective and safe therapy for untreated metastatic EGFR-mutated lung adenocarcinoma. The combination does not alter secondary EGFR-T790M mutations in patients with acquired resistance and is feasible in real-world clinical practice. Graphic Abstract Supplementary Information The online version contains supplementary material available at 10.1007/s40487-021-00152-6.

Immune checkpoint inhibitors (ICIs) are the standard treatment for non-small-cell lung cancer (NSCLC). We assessed the clinical prognostic factors in NSCLC patients receiving atezolizumab as a second- or later-line (2L+) treatment. Data were retrospectively collected for NSCLC patients treated with atezolizumab from July 2017 to June 2019 at six medical centers in Taiwan. Clinical characteristics, treatment course and responses of patients were recorded. A total of 128 NSCLC patients received 2L+ atezolizumab, and the outcomes included a response rate of 10.2%, median progression-free survival (mPFS) of 3.5 months, and median overall survival (mOS) of 10.7 months. Eleven patients who had received osimertinib treatment before atezolizumab had a shorter mPFS (2.3

Second primary cancer is prevalent in patients with gastrointestinal (GI) cancer, for which lung cancer is the most common and associated with high lethality. Image screening for lung cancer was proved to be effective in early diagnosis and lower mortality. However, trials of screen for lung cancer generally excluded patients with a previous diagnosis of malignancy. The study aimed to investigate the outcome of second primary lung cancer and the factor that improve survival in patients with hepato-GI cancer. A total of 276 patients with secondary lung cancer were found among 3723 newly-diagnosed lung cancer patients diagnosed in Chang Gung Memorial Hospital, between 2010 and 2014. Patients’ clinical characteristics, stages and survival were recorded and analyzed. The patients were separated into 2 groups: Group I was defined as lung cancer detected in original primary cancer clinic and group II patients defined as lung cancer detected in other medical places. Sixty-nine cases with primary GI-hepatic and secondary lung cancer were diagnosed (42 (60.8%) in Group I and 27 (39.1%) in Group II). Although both groups had comparable primary cancer stages and treatment, more patients in Group I than Group II were diagnosed as early stage lung cancer (stage I-II: 40.5% vs 11.1%; P = .023). Group II had larger lung tumor sizes than Group I (4.7 vs 3.5 cm; P = .025). Group I showed better 5-year overall survival than Group II (P = .014, median survival: 27 vs 10 months). Among Group II, only 37% had received image follow up in clinic compared with 67% of Group I cases (P = .025). Patients with chest image follow up in clinics also had better 5-year overall survival (P = .043). GI-hepatic cancer was the most common primary malignancy in the lung cancer cohort. Patients had better survival outcome when secondary lung cancer was diagnosed in original primary cancer clinic. Chest image screening strategy may contribute better survival in secondary lung cancer due to detection at an earlier stage.

Background: Although bevacizumab in combination with afatinib or erlotinib is an effective and safe first-line therapy for advanced epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC), there are very few clinical data comparing afatinib and erlotinib combined with bevacizumab. We performed a retrospective multicenter analysis for the comparison of two combination therapies. Methods: Between May 2015 and October 2020, data of 135 stage IIIB/IV EGFR-mutated NSCLC patients receiving first-line afatinib or erlotinib combined with bevacizumab combination therapy in Linkou, Keelung, Chiayi, and Kaohsiung Chang Gung Memorial Hospitals were retrieved and retrospectively analyzed. Results: In all, 67 patients received afatinib plus bevacizumab, and 68 patients received erlotinib plus bevacizumab. Afatinib combined with bevacizumab had an objective response rate (ORR) of 82.1% and a disease control rate (DCR) of 97.0%, and the ORR and DCR were 83.8 and 95.6%, respectively, in the erlotinib combined with bevacizumab group ( p = 0.798 and p = 1.000). The median progression-free survival was 20.7 and 20.3 months for the afatinib plus bevacizumab group and the erlotinib plus bevacizumab group, respectively [hazard ratio (HR) = 1.02; 95% confidence interval (CI), 0.891–1.953; p = 0.167). The overall survival was 41.9 and 51.0 months for the afatinib plus bevacizumab group and erlotinib plus bevacizumab group, respectively (HR = 1.42; 95% CI, 0.829–2.436; p = 0.201). The secondary EGFR-T790M mutation rates after disease progression were 44% in the afatinib plus bevacizumab group and 58.8% in the erlotinib plus bevacizumab group ( p = 0.165). Skin toxicity was the most frequent treatment-related adverse event (AE) in both treatment groups. Diarrhea, an AE, occurred significantly more frequently in the afatinib plus bevacizumab group than in the erlotinib plus bevacizumab group ( p Conclusion: Afatinib combined with bevacizumab was equally as effective as erlotinib combined with bevacizumab for untreated advanced EGFR-mutated NSCLC. Prospective clinical studies that explore bevacizumab combined with afatinib or erlotinib for advanced EGFR-mutated NSCLC are warranted.

Background Malignant endobronchial mass (MEM) has poor prognosis, cryotherapy is reportedly to diagnose MEM, however, the therapeutic role of cryotherapy impacts on survival has not be well addressed. Methods Cohort data on post-cryotherapy MEM patients in a university-affiliated hospital between 2007 and 2012 were evaluated. Factors that impact survival of these subjects were analyzed using multivariate regression analysis. Results During study period, 67 patients (47 males), with median age was 63 years (range, 50–77 and median performance status of 2 (inter-quartile range [IQR], 2–3). Twenty-five had primary lung squamous cell carcinoma, 14 primary had lung adenocarcinoma, seven had metastatic colon adenocarcinoma, four had sarcoma, four had non-small cell lung cancer, four had small cell lung cancer, three had large cell carcinoma, two had lymphoma, one had muco-epidermoid carcinoma, two had esophageal squamous cell carcinoma, and one had metastatic renal cell carcinoma. MEM were observed as follows: 15 at the trachea, 14 at the left main bronchus, 12 at the right main bronchus, 12 at the right upper lobe bronchus, five at the right intermediate bronchus, three at the right lower lobe bronchus, three at the left upper lobe bronchus, two at the left lower lobe bronchus, and one at the right middle lobe bronchus Post-cryotherapy complications included minor bleeding (n = 14) and need for multiple procedures (n = 12); outcomes were relief of symptoms (n = 56), improved performance status (n = 49) and ability to receive chemotherapy (n = 43). After controlling for other variables, performance status improved after cryotherapy (odds ratio [OR] 3.7; p = 0.03; 95% confidence interval [CI] 1.2~10.7) and ability to receive chemotherapy (OR 4.3; p = 0.02; 95% CI 1.4~13.7) remained significant survival factor. Patients who received chemotherapy and cryotherapy had better survival than patients who received only cryotherapy (median, 472 vs. 169 days; log-rank test, p = 0.02; HR 0.37; 95% CI 0.16–0.89). Conclusion Cryotherapy could be useful management of MEM by flexible bronchoscopy. The performance status after cryotherapy improved and caused further chemotherapy possible for the study patients and thereby, improved survival. However, the mechanism in detail of cryotherapy improve survival should be explored in the future.

The efficacy of afatinib in combination with bevacizumab in untreated advanced epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma is currently unclear. We sought to investigate the efficacy of this combination through a multicenter observational analysis. Data for 57 patients with advanced EGFR-mutated lung adenocarcinoma who received afatinib combined with bevacizumab as first-line therapy at the Chang Gung Memorial Hospitals in Linkou and Kaohsiung and Taipei Tzu Chi Hospital from May 2015 to July 2019 were analyzed. The objective response rate and disease control rate of afatinib combined with bevacizumab therapy were 87.7% and 100%, respectively. In all patients, the median progression-free survival (PFS) and overall survival (OS) were 23.9 (95% confidence interval (CI) (17.56&ndash, 29.17)) and 45.9 (95% CI (39.50&ndash, 53.60)) months, respectively. No statistical significance between exon 19 deletion and L858R mutations was noted in PFS or OS. The most frequent adverse events (AEs) were diarrhea (98.2%) and dermatitis (96.5%), and most AEs were grade 2 or lower and manageable. The combination of afatinib and bevacizumab is an effective therapy for untreated advanced EGFR-mutated lung adenocarcinoma with acceptable safety. Future prospective studies focusing on this combination for untreated advanced EGFR-mutated lung adenocarcinoma are warranted.

Background: Precision medicine of asthma requires understanding of its heterogeneity and molecular pathophysiology. Aim: Three sputum-derived transcriptomic clusters (TACs) were previously identified [Kuo at al. Eur Respir J.2017, 49] in the U-BIOPRED cohort: TAC1 consisting of T2 high patients with eosinophilia, TAC2 with neutrophilia and inflammasome activation and TAC3, a more heterogeneous cluster with mostly paucigranulocytic patients. We further refine TAC3. Methods: Gaussian mixture modelling for model-based clustering was applied to sputum gene expression of 104 asthmatic participants from the adult cohort to substructure TAC3. Gene set variation analysis (GSVA) was used to explore the enrichment of gene signatures across the TACs. Results: We again produce the three TACs (TAC1 N=23, TAC2 N=24) but TAC3 was further split into two groups (TAC3a N=28, TAC3b N=29), distinguished by distinct neutrophils and macrophages density and enrichment of IL13 stimulation, inflammasome activation and OXPHOS gene signatures (Figure), as well as IL-4 and LPS-stimulated macrophage gene signatures. However, there were no distinguishing clinical features. Conclusion: Identification of sub-structure of sputum TACs, particularly of TAC3, will help towards improved targeted therapies.

In vitro models have demonstrated immune-modulating effects of bevacizumab (BEV). Combinations of an EGFR tyrosine kinase inhibitor (TKI) with BEV improve progression-free survival (PFS) in patients with EGFR-mutated lung adenocarcinoma. How BEV confers this clinical effect and the underlying mechanisms of its effect are not clear.A total of 55 patients with stage 4 EGFR-mutated lung adenocarcinoma were enrolled. Myeloid-derived suppressor cells (MDSCs), type 1 and type 2 helper T cells, and cytotoxic T lymphocytes were analyzed by flow cytometry. Clinical data were collected for analysis.In all, 25 patients received EGFR TKI and BEV combination therapy (the BEV/TKI group) and 30 patients received EGFR TKI monotherapy (the TKI-only group). The BEV/TKI group had longer PFS (23.0 versus 8.6 months [p = 0.001]) and, in particular, better intracranial control rates (80.0% versus 43.0% [p = 0.03]), a longer time to intracranial progression (49.1 versus 12.9 months [p = 0.002]), and fewer new brain metastases (38.0% versus 71.0% [p = 0.03]) than the TKI-only group did. The BEV/TKI group had a lower percentage of circulating MDSCs (20.4% ± 6.5% before treatment versus 12.8% ± 6.6% after treatment, respectively [p = 0.02]), and higher percentages of type 1 helper T cells (22.9% ± 15.3% versus 33.2% ± 15.6% [p0.01]) and cytotoxic T lymphocytes (15.5% ± 7.2% versus 21.2% ± 5.6% [p0.01]) after treatment, changes that were not seen in the TKI-only group. Pretreatment percentage of MDSCs was correlated with PFS, with this correlation attenuated after BEV/TKI treatment. Percentage of MDSCs was also associated with shorter time to intracranial progression.Combining a EGFR TKI with BEV extended PFS and protected against brain metastasis. Those effects were probably due to the reduction of circulating S100A9-positive MDSCs by BEV, which leads to restoration of effective antitumor immunity. Our data also support the rationale for a BEV-immune checkpoint inhibitor combination.

Background The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) eventually fails in treating advanced lung adenocarcinoma harboring sensitive EGFR mutations because of acquired resistance. In clinical practical setting, platinum-doublet chemotherapy has been frequently performed after failure of first-line EGFR-TKIs. The efficacy of different regimens was compared. Methods From January 2012 to December 2013, 160 patients with mutated EGFR receiving first-line EGFR-TKIs and second-line chemotherapy were analyzed retrospectively. Sixty-eight patients received pemetrexed-based therapy and among them, 61 were in combination with cisplatin. Ninety-two patients received non-pemetrexed-based therapy and among them, 79 were combined with cisplatin. Results The progression-free survival of first-line EGFR-KI was 9.0 and 8.6 months for pemetrexed and non-pemetrexed treatment groups respectively (HR: 0.9146, 95% CI: 0.6656 to 1.257, P =0.5818). The median progression-free survival (PFS) of second-line therapy was 8.3 and 5.6 months for pemetrexed and non-pemetrexed treatment groups respectively (HR: 0.4217, 95% CI: 0.2952 to 0.6025, P =0.0001). The median overall survival (OS) after first-line EGFR-TKIs was 16.9 and 10.3 months for pemetrexed and non-pemetrexed groups respectively (HR: 0.5160, 95% CI: 0.3381 to 0.7873, P =0.0021). For those receiving pemetrexed continuous maintenance therapy, there was 18.7 months of survival after first-line EGFR-TKI, compared to 11.1 months for those without maintenance (HR: 0.4012, 95% CI: 0.2577 to 0.6247, P Conclusion The efficacy of pemetrexed was superior to other chemotherapeutic agents in second line treatment for patients with lung adenocarcinoma harboring sensitive EGFR mutations after first-line EGFR-TKI therapy. Continuous maintenance pemetrexed therapy also improved the PFS and OS.

Background: First-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective for the treatment of lung adenocarcinoma with an EGFR-sensitizing mutation, but resistance is inevitable. Chemotherapy is widely used in the second-line setting. The outcome following this treatment scheme has not been thoroughly evaluated. Methods: From 2007 to 2011, consecutive patients with mutated EGFR receiving first-line TKI and second-line chemotherapy were retrospectively reviewed. The overall response was categorized into double responder, single responder and double nonresponder. Results: Following this treatment scheme, baseline Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (HR 0.60; 95% CI 0.37-0.98; p = 0.041) and double responder (HR 0.24; 95% CI 0.07-0.78; p = 0.018) were independent predictors of overall survival. Absence of pleural metastasis independently predicted the response to first-line TKI (OR 2.60; 95% CI 1.13-5.99; p = 0.025). In TKI responders, ECOG performance status 0-1 before chemotherapy (OR 4.95; 95% CI 1.15-21.28; p = 0.006), an exon 19 deletion (OR 4.74; 95% CI 1.30-17.21; p = 0.018) and progression-free survival (PFS) on first-line TKI (OR 1.02; 95% CI 1.01-1.09; p = 0.049) independently predicted the response to second-line chemotherapy. A moderate linear relationship (Pearson's r = 0.441; p = 0.001) existed between the PFS of this treatment scheme in TKI responders. Conclusion: The status of double responder to first-line TKI and second-line chemotherapy was predictive of improved survival in EGFR-mutated adenocarcinoma.

Objectives: To present the complications of Ultraflex Self-Expandable Metallic Stents (SEMSs) applied in patients with benign tracheobronchial diseases. Methods: Eighty patients received 124 SEMSs were retrospectively reviewed in a tertiary hospital. Results: The baseline characteristics of patients received SEMS implantation including age (mean + standard deviation: 62.5 + 14.8 years), gender (male, 60.5%), smoking (46.8%), forced expiratory volume in first one second (FEV1) (mean + standard deviation, 0.92 +0.41 L/s), follow-up days after SEMS implantation (median (interquartile range); 457 (131 - 897)) and covered SEMS (33.9%) were listed. Symptoms improved after SEMS implantation among 95 patients (76.6%). Time to complications developed was 236 (median; interquartile range, 59 - 672) days. The overall complication rate was 41.9% after SEMS implantation. The complications included SEMS migration (6.5%), granuloma (19.3%) and SEMS fracture (16.1%). Successful management rates of SEMS migration, granuloma and SEMS fracture were up to 100%, 83.3%, and 85% respectively. Conclusions: Patients received SEMS implantation due to benign conditions had poor lung function and were old. The complication rate in patients with benign conditions was high after longer follow-up period, however, successful management achieved in most patients with complications.

Introduction Esophagorespiratory fistula (ERF) caused by esophageal cancer has a poor prognosis. This study describes the clinical effects of airway ultraflex stenting as an alternative method for ERF caused by esophageal cancer. Methods In an university-affiliated hospital, consecutive patients with ERF caused by esophageal cancer and confirmed by bronchoscopy were included. The demography, clinical manifestations and survival between groups with and without airway stenting were compared by case-control study. Results From 2001 to 2007, 817 patients with esophageal cancer received bronchoscopy. Among these patients, 59 patients with ERF were included in this study. The demography and clinical manifestations between groups with and without airway stenting were similar, but survival improved in group with airway stenting, which was compared using log-rank test [ P = 0.04; hazard ratio, 0.56; 95% confidence interval (CI), 0.31–0.99]. After adjusted with age and gender by multinominal logistic regression, airway stenting [adjusted odds ratio (OR), 5.2; P = 0.01; 95% CI, 1.4–18.8], performance status (adjusted OR, 6.1; P = 0.004; 95% CI, 1.8–20.8), further treatment (adjusted OR, 8.7; P = 0.001; 95% CI, 2.3–32.8) and prolonged pneumonia (adjusted OR, 0.14; P = 0.008; 95% CI, 0.03–0.59) remained as significant factors that impacted survival. Conclusions Surgical treatment remains the first choice in patients with esophageal cancer with ERF; however, the authors provided an alternative airway stenting for those patients whom surgery is unsuitable. It improved survival in the group with airway stenting than those without. Performance status improvement and further treatment for esophageal cancer may improve survival, but prolonged pneumonia may worsen survival.

Background: Endobronchial ultrasound-guided transbronchial aspiration (EBUS-TBNA) has the potential to improve nodal diagnosis and staging in non–small cell lung cancer (NSCLC). This study was performed to explore the roles of EBUS-TBNA in NSCLC. Methods: From 2007 to 2009, 164 NSCLC patients were examined by EBUS-TBNA. The patients were divided into a diagnosis group (n = 64) and a staging group (n = 100). Results: For all patients, the diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 92.3%, 100%, 100%, 88.2%, and 95.1%, respectively. In the diagnosis group, the diagnostic sensitivity, specificity, PPV, NPV, and accuracy were 89.7%, 100%, 100%, 86.2%, and 94.4%, respectively. Thirty five patients (54.7%) positive for malignancy as determined by EBUS-TBNA avoided surgery. In the staging group, the diagnostic sensitivity, specificity, PPV, NPV, accuracy, and surgery avoidance rate were 93.8%, 100%, 100%, 89.7%, 96%, and 61%, respectively. Conclusions: EBUS-TBNA is a feasible and effective tool for NSCLC diagnosis and staging that also reduces surgery rates. Patients with NSCLC should initially undergo the less invasive EBUS-TBNA procedure for diagnosis and staging of NSCLC. However, negative findings must be confirmed by surgery.

Introduction Despite removal of airway metallic stents by rigid bronchoscope was presented, there are few reports describing such removal by flexible bronchoscope. Methods 36 patients who had airway Ultraflex stents removed by flexible bronchoscope from 2002 to 2009 were reviewed. Factors contributing to removal method and complications during and after removal were analyzed by multinomial logistic regression. Results Among 36 patients with stent extraction; 17 stents (47.2%) were removed by a single procedure and 19 (52.8%) by multiple procedures. There was no mortality or severe morbidity during or after stent removal. There were 21 complications after stent removal, including retained stent pieces (n = 9), mucosal tear with bleeding (n = 5), and re-obstruction requiring silicone stent placement (n = 7). Stent indwelling time > 10 months (adjusted odds ratio: 9.5; 95% confidence interval: 7.9–11.1, P=0.01), obstructive granulation tissue formation before stent removal (adjusted odds ratio: 5.2; 95% confidence interval: 2.2–8.6, P=0.01), and stent fracture before removal (adjusted odds ratio: 3.5; 95% confidence interval: 1.8–15.4, P=0.04) were independent predictors of the need for multiple procedures for stent removal. Stent indwelling time > 10 months (adjusted odds ratio: 4.2; 95% confidence interval: 2.1–8.9, P=0.01), obstructive granulation tissue formation before stent removal (adjusted odds ratio: 16.5; 95% confidence interval, 1.8–49.6, P=0.01), and multiple procedures required for removal (adjusted odds ratio: 6.9; 95% confidence interval, 1.1–43.5, P=0.04) were independent predictors of removal complications. Conclusions A flexible bronchoscope can be used to remove stents in patients with central airway obstruction and stent-related complications. This procedure should be performed in centers with experienced multidisciplinary teams.

Our study investigated whether tumor-associated macrophages (TAMs) in advanced non-small cell lung cancer (NSCLC) are related to treatment response to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and may be a predictor of survival. Of 206 advanced NSCLC patients treated (first-line) with an EGFR-TKI at the study hospital from 2006 to 2009, 107 with adequate specimens for assessing CD68 immunohistochemistry as a marker of TAMs were assessed. After EGFR-TKI treatment, response was observed in 55 (51%) patients, and the median follow-up period was 13.5 months. Most TAMs were located in the tumor stroma (>95%) and positively costained with the M2 marker CD163. TAM counts were significantly higher in patients with progressive disease than in those without (p < 0.0001), a trend that remained in patients with known EGFR mutation status (n = 59) and those with wild-type EGFR (n = 20). High TAM counts, among other factors (e.g., wild-type EGFR), were significantly related to poor progression-free survival (PFS) and overall survival (OS) (all p < 0.0001 for TAMs). Multivariate Cox analyses showed that high TAM counts and EGFR mutations were both independent factors associated with PFS [odds ratio (OR), 8.0; 95% confidence interval (CI), 2.87-22.4; p = 0.0001 and OR, 0.03; 95% CI, 0.003-0.31; p = 0.003, respectively] and OS (OR, 2.641; 95% CI, 1.08-6.5; p = 0.03 and OR, 0.14; 95% CI, 0.03-0.56; p = 0.006, respectively). TAMs are related to treatment response irrespective of EGFR mutation and can independently predict survival in advanced NSCLC treated with an EGFR-TKI.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) provide promising effect against non-small-cell lung cancer (NSCLC), although most tumors acquire resistance. Our objective was to assess the survival outcome of patients with NSCLC with or without subsequent chemotherapy after acquired TKI resistance.A total of 114 patients with pathologically confirmed stage IIIB or IV NSCLC who had had disease control with TKIs were retrospectively reviewed. After acquired TKI resistance, patients received either best supportive care (BSC) only or BSC plus subsequent chemotherapy. Both groups were well balanced in regard to performance status, age, sex, histology subtype, and smoking status.Sixty-seven patients (58.8%) received subsequent chemotherapy, and 47 patients (41.2%) received BSC only. The median overall survival (OS) and progression-free survival (PFS) from the time of TKI resistance in the subsequent-chemotherapy group (11.2 months and 3.5 months, respectively) were longer than those of the BSC group (3.8 months and 1.5 months, respectively; P.01). Patients who subsequently received taxane-based chemotherapy exhibited higher a response rate and disease control rate (48.7% and 79.5%, respectively) than patients treated with a nontaxane regimen (21.4% and 53.5%, respectively; P.05). Overall survival and PFS in patients after taxane-based subsequent chemotherapy (12.7 months and 5.1 months, respectively) were longer than those of patients given a nontaxane regimen (7 months and 1.8 months, respectively; P.01).This study suggests that acquired TKI resistance should be managed aggressively. The higher antitumor response and survival outcome with a taxane-based regimen in this retrospective study could encourage further prospective investigation to confirm the efficacy of taxane over nontaxane chemotherapy in patients with NSCLC whose disease progresses with EGFR TKI treatment.

Immune aberrations have been demonstrated in tumorogenesis, and myeloid-derived suppressor cells (MDSC) have shown to play a pivotal role in mediating immune suppression in animal models of human tumors. In the present study, we explored the clinical relevance of CD11b+/CD14⁻/CD15+/CD33+ MDSCs and the association of MDSCs with CD8+ cytotoxic T lymphocytes in patients with non-small-cell lung cancer (NSCLC).The population of CD11b+/CD14⁻ cells in peripheral blood mononuclear cells (PBMNC) was determined in 173 patients with NSCLC and 42 control subjects. The expression of CD15, CD33, IL-4R, INF-γR, iNOS and L-arginase were analyzed. Cocultures with CD8+ T lymphocytes and Jurkat cells were developed to determine the impact of MDSCs on the expression of CD3ζ of CD8+ T lymphocytes.Patients with treatment-naïve, advanced-stage NSCLC (n = 87) had an increased subpopulation of CD11b+/CD14⁻/CD15+/CD33+ cells in the PBMNCs with characteristics of MDSCs (P0.0001). The CD11b+/CD14⁻ cells in PBMNC also express IL-4R and INF-γR and can suppress CD3ζ expression in CD8+ T lymphocytes. The subpopulation of CD11b+/CD14⁻ cells in PBMNC was decreased in the advanced-stage NSCLC patients who had responsiveness to chemotherapy (n = 41, P0.0001) and in the early-stage NSCLC patients after removal of tumor (n = 8, P = 0.0391). Notably, a negative association existed between the population of CD11b+/CD14⁻ cells in PBMNC and the frequency of CD8+ T lymphocytes (n = 48, r = -0.3141, P = 0.0297).Our study provided evidence of an increased pool of CD11b+/CD14⁻/CD15+/CD33+ MDSCs in the peripheral blood of NSCLC patients. For the suppressive effect of the cells on CD8+ T lymphocytes, these findings suggest the important role of the CD11b+/CD14⁻/CD15+/CD33+ MDSCs in mediating immunosuppression in NSCLC.

Osler-Weber-Rendu syndrome is a disease of hereditary telangiectasia with involvement of multiple visceral organs. Pulmonary arteriovenous malformation (AVM) is a frequent clinical manifestation, that may mimic pulmonary mass. In this report, endobronchial ultrasound (EBUS) was used in a 64-year-old woman with Osler-Weber-Rendu syndrome who had a solitary pulmonary mass associated with clinical evidence of a right-to-left shunt and was able to detect a pulsating hypoechoic mass connected to the right pulmonary artery suggesting of pulmonary AVM. Following magnetic resonance angiogram and chest CT as well as noting multiple telangiectasis on her skin and considering a strong family history, Osler-Weber-Rendu syndrome was confirmed. Exercise intolerance and desaturation improved after surgical resection of the pulmonary AVM. The echoic findings were correlated to the pathological features. EBUS can be used as a good diagnostic tool for determining the nature of peripheral lung lesions such as in this case, and EBUS may be of practical tool to investigate a lung mass when a vascular component is suspected.

We hypothesized that Gene Set Variation Analysis (GSVA) of gene expression in bronchial brushings can effectively classify airway Th2-high status in U-BIOPRED asthmatics. Airway Th2-status was defined as IL-13-induced transcriptional activity, evaluated as enrichment of IL-13 in-vitro stimulation (IVS) or expression of POSTN and SERPINB2 in human bronchial epithelial cell transcriptomic profiles from U-BIOPRED asthma patients. Based on IL-13 IVS GSVA enrichment scores above the 95 th percentile for healthy subjects, 53% of severe asthma (SA) non-smokers (n=49), 67% of SA smokers (n=18) and 36% of non-severe asthmatics (n=36) were classified as Th2-high. Eosinophilic inflammation marker values are shown in Figure 1. Using the mean normalised expression of POSTN and SERPINB2 as an alternative Th2 stratification factor, 35% of SA non-smokers, 22% of SA smokers, and 14% of non-severe asthmatics were Th2-high, mostly subsets of the IL-13 IVS-defined Th2-high asthma groups and consistent with the modest correlation (r=0.39) between the IL-13 IVS enrichment scores and POSTN/SERPINB2 scores. IL-13 IVS and POSTN/SERPINB2 based definitions of Th2 activity showed associations with eosinophilic and atopy markers, with good agreement for Th2-high vs. -low calls, although the latter approach may be too conservative. IL-13 IVS enrichment identified a broader set of subjects with airway Th2 activity when compared to POSTN and SERPINB2. Funded by IMI.

Rationale: Airway inflammation of asthma involves diverse cell types. We hypothesize that gene expression profile of bronchial biopsy in asthma is associated with specific inflammatory cell infiltration. Methods: Bronchial biopsies were obtained from moderate/severe asthma cohort and gene expression analyzed. Submucosal inflammatory cell counts of eosinophil (EOS), neutrophil (NEU) and CD4+ T cell (CD4) were studied by immunohistochemistry. Each cell type was clustered by partition around medoids and support vector machine (Y Lee et al.Bioinformatics2003 19:1132-39) was used to address classification. Results: 81 biopsy samples were available for analysis. 4 cluster medoids of IHC counts were noted for EOS (0, 2.2, 5.7 and 13.6/mm2), NEU (4.6, 12.1, 20.0 and 50.8/mm2) and CD4 (4.4, 12.2, 35.2 and 111.9/mm2). IHC counts of each higher two medoids (high group) were significantly higher than control. MMP10 (log2FC:1.31, adjusted-p=0.035) and MET (Met proto-oncogene) (log2FC:0.42, adjusted-p=0.035) were differentially expressed in the EOS high group (cutoff 4.0/mm2). The most differentially expressed genes in the CD4 high (DOCK10, adjusted-p=0.175) group did not reach statistical significance. ROC curve showed MMP10 and MET as classifiers of high bronchial EOS (AUC: 0.853, 95%CI: 0.758-0.937, p=3.97e-08), providing the overall best accuracy at 82.7%. Conclusion:MMP10 and MET are novel gene markers of bronchial eosinophilic asthma.

Rationale: Granulocytic inflammation in sputum may be linked to diverse mechanisms. Clustering of the sputum transcriptome may help define granulocyte-specific disease drivers. Methods: In the UBIOPRED cohort, s putum eosinophils (EOS) ≥1.5% was used to define an EOS or ≤1.5% non-EOS phenotype. Differentially-expressed genes (DEGs) were obtained that differentiated between EOS, non-EOS and healthy volunteers (HV). Gene signatures were refined using nearest shrunken centroids algorithm (Robert et al. PNAS 2002, 99; 6567). Results: Clustering of 478 DEGs yielded clusters defined by 3 disease drivers, namely EOS- (n=31) and neutrophil- (NEU, n=31) enriched as well as a non-EOS non-NEU enriched (n=56) cluster (Fig 1). In the EOS-enriched cluster, signature refinement revealed 28 DEGs encoding multiple cytokine receptors and proteases including IL1RL1, TSLPR, CCR3, VSTM1, IL3RA, PRSS33 and CLC . For the NEU-enriched cluster, 27 DEGs mainly related to TNF and interferon regulation were found: TNFIP3, TNFSF10, CASP4, GBP1P1, CLEC4D, IFIT2, IFIH1, IFIT3 and IFI16 . Conclusion: Clustering on sputum cell genes reveal diverse mechanisms associated with sputa from asthma patients, with TNF- and IFN-associated genes in neutrophil-rich sputa.

Background: The alveolar recruitment maneuver (RM) has been reported to improve oxygenation in acute respiratory distress syndrome (ARDS) and may be related to reduced extravascular lung water (EVLW) in animals. This study was designed to investigate the effects of RM on EVLW in patients with ARDS. Methods: An open label, prospective, randomized controlled trial including patients with ARDS was conducted in hospitals in North Taiwan between 2010 and 2016. The patients were divided into 2 groups (with and without RM). The primary endpoint was the comparison of the EVLW index between the 2 groups. Results: Twenty-four patients with ARDS on mechanical ventilator support were randomized to receive ventilator treatment with RM (RM group, n = 12) or without RM (non-RM group, n = 12). Baseline demographic characteristics were similar between the 2 groups. After recruitment, the day 3 extravascular lung water index (EVLWI) (25.3 ± 9.3 vs 15.5 ± 7.3 mL/kg, P = .008) and the arterial oxygen tension/fractional inspired oxygen ratio (PaO2/FiO2) (132.3 ± 43.5 vs 185.6 ± 38.8 mL/kg, P = .003) both improved over that of day 1. However, both EVLWI and PaO2/FiO2 did not significantly change from day 1 to 3 in the non-RM group. Conclusion: RM is a feasible method for improving oxygenation and the EVLW index in patients with ARDS, as well as for decreasing ventilator days and intensive care unit stay duration.

Background Central airway obstruction related to endobronchial malignancy is one of the most difficult oncological complications and requires efficient palliative intervention. Methods Fifty-three consecutive patients with unresectable endobronchial malignancy receiving bronchoscopic cryotherapy as palliative treatment were retrospectively reviewed. Efficiency was evaluated by the improvement of performance status (PS), and the best achievement of tumor removal was assessed as complete or partial removal. Result Patients' PS after cryotherapeutic tumor removal improved from the baseline PS (P = 0.006). In multivariate logistic regression analysis, the compression part of the tumor (odds ratio [OR] 0.42; 95% confidence interval [CI] 0.23∼0.75, P = 0.004) and the thin tumor stalk (OR 87.86; 95% CI 2.31∼3337.37, P = 0.016) were independent predictors of complete tumor removal. Tumors larger than 9.3 cm, including compression and invasion parts, had the highest odds of being only partially removed (positive predictive value [PPV]: 88.2%, likelihood ratio [LR]+: 10.49); tumors smaller than 9.3 cm were likely to be completely removed (negative predictive value [NPV]: 80.6%, LR−: 0.34). After cryotherapy, re-obstruction was significantly associated with non-squamous cell carcinoma (65.7 vs. 16.7%, P = 0.001) and patients who had longer overall survival (11.7 vs. 1.5 months, P < 0.001). Odds of tumor re-obstruction increased 2.28-fold (PPV: 81.6%, LR+: 2.28) beyond two months; the odds decreased by 81% (NPV: 73.3%, LR−: 0.19) within two months. Conclusion Debulking of a tumor using cryotherapy is a useful palliative treatment for endobronchial obstruction secondary to a variety of malignancies.

Although malignant endobronchial mass (MEM) has poor prognosis, cryotherapy is reportedly a palliative treatment. Clinical data on postcryotherapy MEM patients in a university-affiliated hospital between 2007 and 2011 were evaluated. Survival curve with or without postcryotherapy chemotherapy and performance status (PS) improvement of these subjects were analyzed using the Kaplan-Meier method. There were 59 patients (42 males), with median age of 64 years (range, 51–76, and median performance status of 2 (interquartile range [IQR], 2-3). Postcryotherapy complications included minor bleeding (n=12) and need for multiple procedures (n=10), while outcomes were relief of symptoms (n=51), improved PS (n=45), and ability to receive chemotherapy (n=40). The survival of patients with chemotherapy postcryotherapy was longer than that of patients without such chemotherapy (median, 534 versus 106 days; log-rank test,P=0.007; hazard ratio, 0.25; 95% confidence interval, 0.10–0.69). The survival of patients with PS improvement postcryotherapy was longer than that of patients without PS improvement (median, 406 versus 106 days; log-rank test,P=0.02; hazard ratio, 0.28; 95% confidence interval, 0.10–0.81). Cryotherapy is a feasible treatment for MEM. With better PS after cryotherapy, further chemotherapy becomes possible for patients to improve survival when MEM caused dyspnea and poor PS.

Background: Despite the use of anatomic resection, the post-surgical recurrence rate remains high in early-stage non-small cell lung cancer (NSCLC). Chronic infl ammation plays a role in the mechanism that promotes tumor initiation. This study aimed to investigate the association between recurrence outcome and chronic infl ammation-related co-morbidities in early-stage resected NSCLC. Methods: A review of medical records for recurrence outcome and co-morbidities, in terms of chronic obstructive pulmonary disease (COPD), DM, asthma and cardiovascular diseases, was performed with 181 patients with stage I NSCLC that underwent anatomic resection. Results: Subjects with T descriptors as T2a disease (49.5 vs. 28.0%, p < 0.05) and the presence of COPD (42.4 vs. 20.7%, p < 0.01) had a higher risk of tumor recurrence. Univariate analysis for recurrence-free survival showed T descriptor as T2a (21.5 months vs. NR, p < 0.05) and the presence of COPD (20.5 months vs. NR, p < 0.01) as signifi cant factors predicting reduced survival. The presence of COPD (HR: 1.98; 95% CI, 1.29–.02, p < 0.01) and T descriptor as T2a (HR: 2.01; 95% CI, 1.04–3.91, p < 0.05) remain independent predictors of reduced recurrence-free survival in the Cox regression model. Patients with COPD were at higher risk of brain recurrence (OR: 7.88; 95% CI, 1.50–41.3, p < 0.01). In contrast, patients without COPD showed a tendency toward recurrence in bone and liver (OR: 4.13; 95% CI, 1.08–15.8, p = 0.05). Conclusion: Subjects with COPD and T2a disease had a higher risk of recurrence. The role of COPD as a recurrence promoter merits further prospective investigation.

Background Obstructive sleep apnoea (OSA) has recently been identified as a possible aetiology for chronic cough. The aim of this study was to compare the incidence of chronic cough between patients with and without OSA and the impact of continuous positive airway pressure (CPAP) treatment in resolving chronic cough. Methods Patients referred to the sleep laboratory from January 2012 to June 2012 were retrospectively enrolled. Clinical data, treatment course and resolution of chronic cough were analysed. Specifically, gastro-oesophageal reflux (GERD), upper airway cough syndrome, asthma, apnoea-hypopnoea index and the impact of CPAP treatment on chronic cough were assessed. Results A total of 131 patients were reviewed. The incidence of chronic cough in the OSA group was significantly higher than the non-OSA group (39/99 (39.4%) vs. 4/32 (12.5%), p = 0.005). Both GERD and apnoea-hypopnoea index were significantly associated with chronic cough in univariate analysis. After multivariate logistic regression, GERD was the only independent factor for chronic cough. Moreover, the resolution of chronic cough was more significant in the OSA patients with CPAP treatment compared with those not receiving CPAP treatment (12/18 (66.7%) vs. 2/21 (9.5%), p = 0.010). Conclusion The incidence of chronic cough was significantly higher in the OSA patients. In addition, CPAP treatment significantly improved chronic cough. Therefore, OSA may be a contributory factor to chronic cough.

OBJECTIVES: The diagnosis of peripheral pulmonary lesions (PPLs) often involves endobronchial ultrasound (EBUS)-guided transbronchial biopsy (TBB), washing and brushing. Certain echoic features of PPL have been associated with biopsy yield. This study compared yields of TBB and bronchial washing (TBBW) with those of TBBW plus bronchial brushing and analysed the associations between clinical and echoic features and yield. METHODS: We performed a retrospective review of 271 patients undergoing TBB for PPL. TBBW was performed in 139 patients and 132 underwent TBBW plus brushing. RESULTS: The diagnostic yield of TBBW plus brushing was superior to that of TBBW (80.3 vs 66.2%, P< 0.01). In TBBW patients, lesions

Background: Alfentanil in combination with propofol produces a synergistic sedative effect in patients undergoing flexible bronchoscopy (FB). However, the use of this combination is controversial due to the risk of cardiopulmonary depression. The aim of this study was to evaluate the proper induction regimen of alfentanil in propofol target-controlled infusion for FB sedation. Methods: One hundred seventy-three patients were assigned randomly into 5 regimens: Group 1 and 2, alfentanil 2.5 and 5 μg/kg, respectively, immediately before propofol administration; Group 3 and 4, alfentanil 2.5 and 5 μg/kg, respectively, 2 minutes before propofol administration; and Group 5, propofol administration alone to achieve the observer assessment of alertness and sedation scale 3∼2. The bronchoscopists, physicians in charge of sedation, and patients were blind to the regimens. Adverse events, drug dose, induction, procedure and recovery time, cough severity, and propofol injection related pain were recorded. Results: The patients in groups 2 and 4 required a lower dose of propofol (P = 0.031 and 0.019, respectively) and shorter time (P = 0.035 and 0.010) than group 5 for induction. Patients in group 2 experienced more hypoxemia than those in group 5 during induction (P = 0.031). The physician in charge of sedation scored a lower severity of cough in the patients in group 4 than in groups 3 and 5. There were no differences in terms of propofol injection related pain among the groups. Conclusion: Alfentanil 5 μg/kg given immediately before propofol infusion cannot be recommended. Further study is required to define conclusions about alfentanil 2.5 and 5 μg/kg because of the low power rating of subgroup in the present study.

Background Adjuvant tumor cell vaccine with chemotherapy against non-small cell lung cancer (NSCLC) shows limited clinical response. Whether it provokes effective cellular immunity in tumor microenvironment is questionable. Concomitant active tuberculosis in NSCLC (TBLC) resembles locoregional immunotherapy of tumor cell vaccine; thus, maximally enriches effective anti-tumor immunity. This study compares the survival and immunological cell profile in TBLC over NSCLC alone. Methods Retrospective review of NSCLC patients within 1-year-period of 2007 and follow-up till 2010. Results A total 276 NSCLC patients were included. The median survival of TBLC is longer than those of NSCLC alone (11.6 vs. 8.8 month, p

Introduction Most studies related to healthcare-associated infection with Acinetobacter baumannii (HAIA) are on acutely ventilated patients. Little is known regarding the incidence and outcomes of HAIA in chronically ventilated patients. Methods A retrospective study of chronically ventilated patients covering the period May 2002 to May 2008 was conducted to determine the incidence of patients with HAIA. The Cox proportional hazard model was used to estimate differences in the 30-day mortality between those with and those without HAIA by case-control study after controlling for confounders. Results Of 240 patients who were chronically ventilated for 49,207 days, 78 (32.5%) acquired HAIA at a rate of 1.59/1,000 patient day. The central venous catheter-related bloodstream infections rate was 8.78 per 1,000 catheter days; the ventilator-associated pneumonia rate was 1.26 per 1,000 ventilator days; and the catheter-associated urinary tract infections rate was 0.17 per 1,000 catheter days. Fifty (64.1%) HAIA and 58 (64.4%) non-HAIA patients were treated well and survived without ICU admission. After univariate and multivariate analyses, prolonged ventilation days (odds ratio: 3.4; 95% confidence interval: 1.7-6.1; P = 0.01] and inappropriate empiric antibiotics within 48 hours (odds ratio: 7.9; 95% confidence interval: 3.9-9.8; P = 0.02) were independent factors that predicted the 30-day mortality of HAIA among chronically ventilated patients. Conclusions Although chronically ventilated patients with HAIA have longer ventilator days, higher antibiotics resistance, and high rate per 100 patients of ventilator-associated pneumonia, most patients are treated well. Compared with patients without HAIA, prolonged ventilation days and inappropriate empiric antibiotics within 48 hours are independent factors of the 30-day mortality.

Nodular sarcoidosis comprises less than 5% of cases of sarcoidosis and predominantly shows pulmonary infiltrations. Necrotizing sarcoid granulomatosis (NSG) was first described in 1973 by Liebow, and is best characterized as a variant of nodular sarcoidosis. NSG has the unique picture of infarction-like necrosis within granulomatous lesions, thereby posing a challenge of differentiating it from tuberculosis. Essentially, the diagnosis relies heavily on exclusion of possible causes of granulomatous inflammation. A 35-year-old man with fever and night sweating presented a personal history of significant exposure to pulmonary tuberculosis. His father, with whom he had close contact, had been diagnosed with open tuberculosis 6 months before onset of his symptoms. The sputum acid-fast stain and mycobacterial cultures for tuberculosis were both negative; however, a tuberculin skin test with purified protein derivative was positive by an increment of induration greater than 15 mm. Chest computed tomography (CT)

The endobronchial ultrasound (EBUS) features of peripheral pulmonary lesions (PPLs) are associated with histopathologic presentation. Certain histologic and radiologic characteristics of peripheral pulmonary lesions affect the diagnostic yield of transbronchial lung biopsies (TBLB). This study aimed to assess the feasibility of EBUS echoic features as predictors of diagnostic yield of TBLB. Four hundred and eight patients with PPLs underwent TBLB. The yields of TBLB in lesions with characteristic EBUS features were compared with those without such features. The overall diagnostic yield of TBLB was 64.2%. Lesion diameter (≥3 cm vs.

Objectives: Docetaxel and pemetrexed have been validated as therapeutics for previously treated advanced non-small-cell lung cancer (NSCLC), but tolerability is a concern for standard treatment with docetaxel administered once every 3 weeks (tri-weekly 75-mg/m2 schedule). We conducted this retrospective study to compare the efficacy and toxicity of weekly low-dose docetaxel versus tri-weekly pemetrexed for previously treated advanced NSCLC. Methods: Consecutive patients who received low-dose single docetaxel (30 mg/m2 on days 1 and 8 every 3 weeks) or pemetrexed (500 mg/m2 every 3 weeks) at a single university-affiliated hospital following failure of previous treatment were retrospectively reviewed. Their outcomes and toxicity profiles were determined. Results: 179 patients were included between 2005 and 2008 (docetaxel, n = 79; pemetrexed, n = 100). Both groups had similar hematologic (16.5 vs. 15.0%; p = 0.84) and non-hematologic (20.3 vs. 24%; p = 0.55) toxicities. After controlling for confounding factors, docetaxel remained superior to pemetrexed for progression-free survival (median 4.0 vs. 2.4 months; hazard ratio 0.64; 95% CI 0.47–0.87; p = 0.005) and overall survival (median 15.0 vs.8.5 months; hazard ratio 0.54; 95% CI 0.38–0.77; p Conclusion: Although this study showed that weekly low doses of docetaxel were as tolerable as pemetrexed for previously treated advanced NSCLC, a prospective design is needed to confirm this finding.

Background Endobronchial ultrasonography (EBUS) is useful in localizing peripheral lung lesions. Previous reports have revealed that several characteristic echoic patterns correlate well with the histopathologic findings of benign and malignant lesions. Therefore, EBUS may be also useful in the differential diagnosis of malignant lesions of the lung. Objective To assess the feasibility of EBUS in the differential diagnosis between malignant and benign lesions by the following three characteristic echoic features indicating malignancy: continuous margin; absence of a linear-discrete air bronchogram; and heterogeneous echogenicity. Method EBUS images from 224 patients who undergone bronchoscopy for a peripheral lung lesion were analyzed. The sensitivity and specificity for each echoic feature or in combination in diagnosing malignancy or benignity were determined. Result Continuous margin, absence of linear-discrete air bronchogram, and heterogeneous echogenicity are three echoic features indicating malignancy. The absence of linear-discrete air bronchogram has the highest sensitivity in the diagnosis of malignancy (91.9%), but the lowest specificity (62.4%). By contrast, a well-defined margin has the highest specificity (93.1%), but the lowest sensitivity (27.6%). The sensitivity and specificity for heterogeneous echogenicity are intermediate (65.0% and 90.1%, respectively). The negative predictive value for the malignancy of a lesion with none of these three echoic features is 93.7%. The positive predictive value for malignancy of a lesion with any two of the three echoic features is 89.2%. Conclusion These results indicate that EBUS is useful as an adjunct in lung cancer diagnosis, especially when peripheral lung lesions are not visible in traditional bronchoscopy.

To determine plasma concentrations of angiopoietin (Ang)-1, Ang-2, Tie-2, and vascular endothelial growth factor (VEGF) in patients with sepsis-induced multiple organ dysfunction syndrome (MODS) and determine their association with mortality. The study prospectively recruited 96 consecutive patients with severe sepsis in a l intensive care unit of a tertiary hospital. Plasma Ang-1, Ang-2, Tie-2, and VEGF levels and MODS were determined in patients on days 1, 3, and 7 of sepsis. Univariate and Cox proportional hazards analysis were performed to develop a prognostic model. Days 1, 3, and 7 plasma Ang-1 concentrations were persistently decreased in MODS patients than in non-MODS patients (day1: 4.0 ± 0.5 vs 8.0 ± 0.5 ng/mL, P

Background This study was designated to investigate whether increased extravascular lung water index (EVLWI) may correlate multiple organ dysfunction syndrome (MODS) and mortality in sepsis. Methods We designed a prospective cohort study in an intensive care unit of a tertiary care hospital. Sixty-seven patients with severe sepsis were included. Data were used to determine an association between EVLWI and the development of MODS and mortality. These connections were determined by the multiple logistic regression, plotting the receiver operating characteristic (ROC) curve and by Spearman test. Results EVLWI levels were higher in MODS patients on day 1 (median (IQR), 18(12.8–23.9) ml/kg, n = 38, p