Severe acute lung injury (ALI) can cause death, and the survivals may develop acute respiratory distress syndrome (ARDS) due to fibrotic repair of the lung. Alveolar macrophages play a demonstrative role during the pathogenesis of ALI, and the timing and degree of differentially polarization of macrophages determine the severity of disease and outcome. Exosomes are important mediators of cellular communication and play critical roles during macrophage differentiation, proliferation and function. Nevertheless, the exact effects of alveolar macrophage-derived exosomes on ALI remain unknow. Here, we used lipopolysaccharide (LPS) to induce ALI in mice and analyzed the exosome population in bronchoalveolar lavage fluid (BALF) from macrophages, neutrophils and epithelial cells at different time points after treatment. Our data showed that macrophages were the major secretors for early secreted pro-inflammatory cytokines in the BALF-exosomes, which likely activated neutrophils to produce a variety of pro-inflammatory cytokines and IL-10. IL-10 by neutrophils in BALF-exosomes likely in turn polarized macrophages to M2c, which may be responsible for post-ALI fibrosis. Our study thus reveals a previous non-acknowledged role of BALF-exosomes as a mediator of inflammatory response and cell crosstalk during ALI.

Background: This study aimed to evaluate the survival of the advanced non-small cell lung cancer (NSCLC) patients underwent salvage surgeries after EGFR-TKI neoadjuvant therapies.Methods: From 2014 to 2016, 10 patients diagnosed as advanced stage NSCLC (N2 metastasis or great vessels invasion) who responded to EGFR-TKI neoadjuvant therapy were recruited in this study. All patients underwent surgeries and consented the follow-up study.Results: All patients received successful radical surgeries (complete resection of the tumor with systematic lymphadenectomy). Among them, one patient passed away 7 days post-operatively due to respiratory failure.The pathology of the lesions and the lymph nodes suggested the replacement of tumors by fibrotic tissue, and concentration of focal residual tumors limited in areas of fibrous stroma and lymphocyte infiltration.Adjuvant therapy of EGFR inhibitor gefitinib for at least 6 months was applied to each patient. Each of the patients was followed up with contrasted CT scan, ultrasonography, bronchoscope and tumor markers for at least 8 months (8-30 months, median time: 24 months). The progression-free survival of these patients was 14 months since neoadjuvant therapy.Conclusions: EGFR-TKI neoadjuvant therapy is feasible and effective, along with surgery may improve the surgical rate and survival of advanced NSCLC patients.

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Background: The appropriate surgical modality for early-stage non-small cell lung cancer (NSCLC) among the elderly remains controversial; identifying appropriate modalities will be helpful in clinical practice. Methods: It's a cohort study and we explored the Surveillance, Epidemiology, and End Results (SEER) database for identifying patients aged ≥70 years with pathologic stage IA NSCLC. Three types of surgeries were compared (lobectomy, segmentectomy, and wedge resection) via survival and stratification analyses.Results: Overall, 6,197 patients were enrolled. Among patients aged ≥76 years with tumor diameters ≤1 cm, significant differences in survival were noted for segmentectomy vs. lobectomy [hazard ratio (HR) =0.294, P=0.007] and wedge resection vs. lobectomy (HR =0.548, P=0.017) but not in those with tumors diameters >1 cm. Among patients aged 70-75 years with tumor diameters >1-2 cm, significant differences in survival were observed for segmentectomy vs. lobectomy (HR =0.671, P=0.037) and segmentectomy vs. wedge resection (HR =0.556, P=0.003) and for wedge resection vs. lobectomy (HR =1.283, P=0.003) among those with tumor diameters >2-3 cm but not in those with tumor diameters ≤1 cm. Conclusions: Both age and tumor size should be considered when selecting the surgical modality.Lobectomy is not recommended for lesions ≤1 cm among patients aged ≥76 years. Segmentectomy was associated with superior prognosis for tumor diameters >1-2 cm and survival favored lobectomy rather than wedge resection for NSCLCs >2-3 cm among patients aged 70-75 years. Surgeons could rely on personal experience to determine the appropriate surgical modality for NSCLCs >1 cm among patients aged ≥76 years and NSCLCs ≤1 cm among patients aged 70-75 years.

ObjectiveThis study was to define preoperative predictors from radiologic findings for the pathologic risk groups based on long-term surgical outcomes, in the aim to help guide individualized patient management.MethodsWe retrospectively reviewed 321 consecutive patients with clinical stage IA lung adenocarcinoma with ground glass component on computed tomography (CT) scanning. Pathologic diagnosis for resection specimens was based on the 2011 IASLC/ATS/ERS classification of lung adenocarcinoma. Patients were classified into different pathologic risk grading groups based on their lymph node status, local regional recurrence and overall survival. Radiologic characteristics of the pulmonary nodules were re-evaluated by reconstructed three-dimension CT (3D-CT). Univariate and multivariate analysis identifies independent radiologic predictors from tumor diameter, total volume (TV), average CT value (AVG), and solid-to-tumor (S/T) ratio. Receiver operating characteristic curves (ROC) studies were carried out to determine the cutoff value(s) for the predictor(s). Univariate cox regression model was used to determine the clinical significance of the above findings.ResultsA total of 321 patients with clinical stage IA lung adenocarcinoma with ground glass components were included in our study. Patients were classified into two pathologic low- and high- risk groups based on their distinguished surgical outcomes. A total of 134 patients fell into the low-risk group. Univariate and multivariate analyses identified AVG (HR: 32.210, 95% CI: 3.020–79.689, P<0.001) and S/T ratio (HR: 12.212, 95% CI: 5.441–27.408, P<0.001) as independent predictors for pathologic risk grading. ROC curves studies suggested the optimal cut-off values for AVG and S/T ratio were-198 (area under the curve [AUC] 0.921), 2.9 (AUC 0.996) and 54% (AUC 0.907), respectively. The tumor diameter and TV were excluded for the low AUCs (0.778 and 0.767). Both the cutoff values of AVG and S/T ratio were correlated with pathologic risk classification (p<0.001). Univariate Cox regression model identified clinical risk classification (RR: 3.011, 95%CI: 0.796–7.882, P = 0.095) as a good predictor for recurrence-free survival (RFS) in patients with clinical stage IA lung adenocarcinoma. Statistical significance of 5-year OS and RFS was noted among clinical low-, moderate- and high-risk groups (log-rank, p = 0.024 and 0.010).ConclusionsThe AVG and the S/T ratio by reconstructed 3D-CT are important preoperative radiologic predictors for pathologic risk grading. The two cutoff values of AVG and S/T ratio are recommended in decision-making for patients with clinical stage IA lung adenocarcinoma with ground glass components.

Background The combination of immune checkpoint inhibitors (ICIs) and chemotherapy has been the standard first-line treatment for advanced non-small cell lung cancer (NSCLC) patients with driver-gene negative. However, efficacy biomarkers for ICIs-based combination therapy are lacking. We aimed to identify potential factors associated with outcomes of ICIs plus chemotherapy at baseline and dynamic changes in peripheral blood. Methods We collected plasma samples of 51 advanced NSCLC patients without EGFR/ALK/ROS1 alteration at baseline and/or after two treatment cycles of ICIs plus chemotherapy. A blood-based intratumor heterogeneity (bITH) score was calculated based on the allele frequencies of somatic mutations using a 520-gene panel. bITH-up was defined as a ≥ 10% increase in bITH score from baseline, with a second confirmatory measurement after treatment. Results At baseline, the number of metastatic organs and lung immune prognostic index (LIPI) were significantly associated with shorter progression-free survival (PFS) of ICIs plus chemotherapy, while bITH and other common molecular biomarkers, including ctDNA level, blood-based tumor mutational burden (bTMB), and PD-L1 expression, had no effect on PFS. LRP1B mutation at baseline was significantly associated with favorable outcomes to ICIs plus chemotherapy. There were 37 patients who had paired samples at baseline and after two cycles of treatment, with the median interval of 53 days. Intriguingly, patients with bITH-up had significant shorter PFS (HR, 4.92; 95% CI, 1.72–14.07; P = 0.001) and a lower durable clinical benefit rate (0 vs 41.38%, P = 0.036) than those with bITH-stable or down. Case studies indicated that bITH was promising to predict disease progression. Conclusions The present study is the first to report that increased bITH is associated with unfavorable outcomes of ICIs plus chemotherapy in advanced NSCLC patients.

A 55-year-old man was re-admitted for persistent hemoptysis and high fever three weeks after an initial left upper sleeve lobectomy for a central squamous lung cancer tumor. Pulmonary artery pseudoaneurysm and pulmonary infection were confirmed by multidetector computed tomography angiography and subsequent emergency completion pneumonectomy. The development of pulmonary artery pseudoaneurysm, secondary to post-operative pulmonary infection and pulmonary vascular manipulation, is rare and prompt surgical manipulation is mandatory.

Background: Thymic carcinoma is a type of rare and highly malignant tumor. Limited information was available on prognostic factors of late-stage thymic carcinoma. The aim of this study was to identify factors that impact prognosis and to define the relationship between survival and surgical intervention in patients with Masaoka stage IV thymic carcinoma. Methods: From 1973 to 2015, a total of 311 consecutive patients were enrolled in this study with pathologic confirmed Masaoka stage IV thymic carcinoma from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier analyses, Cox-regression analyses and propensity score matching (PSM) were performed to evaluate prognosis. Results: In the multivariate analysis, larger tumor size, distant metastasis and positive lymph node status were associated with poorer outcome. After PSM, no receipt of surgery was the prognostic factor indicating poorer survival [hazard ratio (HR) 1.985, 95% confidence interval (CI) 1.007-3.913, P=0.048 for overall survival (OS); HR 1.649, 95% CI: 1.009-2.697, P=0.046 for disease-specific survival (DSS)]. Subgroup analysis indicated that significantly improved survival with surgery was observed in patients who were <60 years (HR 0.