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Background Brain metastases (Bmets) are frequent; however, limited data exist on the efficacy of immunotherapy in these lesions. The aims of the study were to analyze the immunohistochemical expressions of programmed death ligand 1 (PD-L1) and CD8 in Bmets and to compare them with their expressions in paired primary tumors, as well as correlate the results with clinicopathological features.Methods This is a retrospective study of 233 patients with Bmets and 111 paired primaries. Clinical, histological, and molecular data were recorded and compared with the immunohistochemical results of PD-L1 and CD8 expressions. The statistical analysis included χ2 test, Cramer’s V test, factorial analyses of variance, simple regression analysis, and Kaplan-Meier analysis with log-rank product limit estimation.Results PD-L1 expression was found in 23.6% of Bmets and in 29.0% of primary tumors with concordant expression between them in 75.5% of cases. Bmets PD-L1 expression was associated with primary tumor PD-L1 expression and the primary tumor type. Significant CD8 peritumoral expression was found in 68.6% of Bmets and in 87.7% of primary tumors. CD8 expression was concordant between primary and metastatic tumors in 73.3% of cases. Bmets CD8 expression was associated with primary tumor CD8 expression and primary tumor type. PD-L1 expression was associated with CD8 expression in both primary and metastatic tumors. The concordance between primary and metastatic tumor PD-L1 expression was independent of all factors studied. The concordance between primary and metastatic CD8 expressions was marginally associated to the time of Bmets development. No prognostic role for PD-L1 and CD8 expression in Bmets was found.Conclusion PD-L1 and CD8 Bmets expressions are associated with the primary tumor type and its PD-L1 and CD8 expressions. No factor predicts the discordance for PD-L1 expression, while time to Bmets development is associated with CD8 expression discordance.

Background. Obstructive sleep apnea syndrome (OSAS) is associated with systemic inflammation and increased risk of cardiovascular and chronic kidney disease. Cystatin C (Cyst C) is a novel biomarker of both latent renal damage and cardiovascular disease. Aim of the study was to measure serum levels of Cyst C, as well as IL-8 and CRP, in otherwise healthy OSAS patients. Methods. 84 individuals examined with polysomnography for OSAS symptoms without known comorbidities were prospectively recruited. Results. According to apnea hypopnea index (AHI) subjects were divided in two groups: OSAS group (AHI > 5/hour, n=64) and controls (AHI < 5/hour, n=20), which were age- and BMI-matched. Cyst C levels were higher in OSAS patients versus controls (1176.13±351.33 versus 938.60±245.83 ng/mL, resp.; p=0.017) while serum IL-8 and CRP levels did not differ significantly. Positive correlation was found between Cyst C levels and respiratory disturbance index (RDI) (r=0.240, p=0.039) and percentage of time with oxygen saturation

Primary tumors of the trachea are rare. Such cases are presented with acute respiratory distress demanding immediate therapeutic intervention. Herein, we present a case of an unresectable second primary tracheal cancer treated with intraluminal brachytherapy (8 Gy at 1 cm from catheter) followed by a short course of external beam hypofractionated radiotherapy (4.5 Gy × 4 fractions) and a final brachytherapy fraction (8 Gy), delivering a biological dose higher than 57.5 Gy (for α/β = 4 Gy) to the tumor within 4 weeks. Concurrent chemotherapy consisted of: fluoruracil (1000 mg/m2),leucovorin (100 mg/m2), oxaliplatin (80 mg/m2) and cetuximab (500 mg/m2), administered every two weeks for two consecutive cycles. Complete response was evident during the second brachytherapy fraction and the patient is alive with no evidence of disease, two years after therapy, without any late radiation sequel.

Mucus gland adenoma is an extremely rare benign lung tumor, presumed to arise from the bronchial mucus glands; it is a TTF-1 negative tumor, centrally located, causing the clinical manifestations of obstruction. We report a TTF-1 negative mucus gland adenoma, arising into the medial bronchopulmonary segment, lacking any relation to a bronchus.

Background Smoking and smoking cessation are considered to be associated with weight changes. We have recently shown that smoking acutely increases plasma levels of ghrelin, a known orexigenic hormone. Obestatin is a peptide encoded by the ghrelin gene, which opposes ghrelin effects on food intake. We conducted a study in adult volunteers measuring plasma levels of obestatin immediately after initiation of smoking. Methods 31 volunteers (mean age 32.2 ± 9.2 years and mean BMI 25.7 ± 4.1), 17 smokers and 14 non-smokers, were enrolled in our study. The 2 groups were matched in age and BMI. Plasma obestatin concentrations were determined at baseline (T0), 2 (T2), 5 (T5), 15 (T15), and 60 (T60) minutes after the initiation of smoking. Results In all 31 subjects, no significant difference in the mean values of plasma obestatin levels was observed from baseline at T2, T5, T15 and T60 after initiation of smoking (overall p = 0.15). However, a trend for higher obestatin levels was noted in smokers vs non-smokers (overall p = 0.069), which was not related to the pack-years. Conclusion On the contrary with ghrelin's response after smoking initiation, there is no such an acute response of plasma obestatin levels.

Introduction: Regenerative medicine and particular adult stem cells represent an alternative option with several fruitful therapeutic applications in patients suffering from chronic lung diseases including idiopathic pulmonary fibrosis (IPF). Nevertheless, lack of knowledge regarding the origin and the potential of mesenchymal stem cells (MSCs) to differentiate into fibroblasts has limited their use for the treatment of this dismal disease. Patients and methods: To this end, we conducted a phase Ib, non-randomized, clinical trial to study the safety of three endobronchial infusions of autologous adipose derived stromal cells (ADSCs)-stromal vascular fraction (SVF) (0.5 million cells per kgr of body weight per infusion) in patients with IPF (n=14) of mild to moderate disease severity (forced vital capacity -FVC>50% predicted value and diffusion lung capacity for carbon monoxide-DLCO>35% of predicted value). Our primary end-point was incidence of treatment emergent adverse events within 12 months. Alterations of functional, exercise capacity and quality of life parameters at serial time points (baseline, 6 and 12 months after first infusion) were exploratory secondary end-points. Results: No cases of serious or clinically meaningful adverse events including short-term infusional toxicities as well as long-term ectopic tissue formation were recorded in all patients. Detailed safety monitoring through several time-points indicated that cell-treated patients did not deteriorate in both functional parameters and indicators of quality of life. Conclusions: The clinical trial met its primary objective demonstrating an acceptable safety profile of endobronchially administered autologous ADSCs-SVF. Our findings accelerate the rapidly expanded scientific knowledge and indicate a way towards future efficacy trials. [ABSTRACT FROM AUTHOR]