The Timing, Trajectory, and Incidence of Immune-Related Adverse Events in NSCLC Treated With Atezolizumab.

Introduction: Immune-related adverse events (irAEs) due to immune checkpoint inhibitors can have complicated clinical courses. We comprehensively evaluated the timing, trajectory, and incidence of both single and multiple irAEs for NSCLC treated with atezolizumab.

Methods: Data were pooled from 2457 patients who participated in the IMpower130, IMpower132, and IMpower150 clinical trials investigating the use of atezolizumab in metastatic NSCLC as part of a chemoimmunotherapy regimen.

Neoadjuvant Targeted Therapy in Resectable NSCLC: Current and Future Perspectives.

The standard of care (SoC) for medically operable patients with early-stage (stages I-IIIB) NSCLC is surgery combined with (neo)adjuvant systemic therapy for patients with stages II to IIIB disease and some stage IB or, rarely, chemoradiation (stage III disease with mediastinal lymph node metastases). Despite these treatments, metastatic recurrence is common and associated with poor survival, highlighting the need for systemic therapies that are more effective than the current SoC. After the success of targeted therapy (TT) in patients with advanced NSCLC harboring oncogenic drivers, these agents are being investigated for the perioperative (neoadjuvant and adjuvant) treatment of patients with early-stage NSCLC.

Association of Immune-Related Adverse Events With Efficacy of Atezolizumab in Patients With Non-Small Cell Lung Cancer: Pooled Analyses of the Phase 3 IMpower130, IMpower132, and IMpower150 Randomized Clinical Trials.

Importance: Immune-related adverse events (irAEs) arising from immune checkpoint inhibitor (ICI) cancer therapy may potentially predict improved outcomes.

Objective: To evaluate the association between irAEs and atezolizumab efficacy in patients with advanced non-small cell lung cancer (NSCLC) using pooled data from 3 phase 3 ICI studies.

Design, Setting, And Participants: IMpower130, IMpower132, and IMpower150 were phase 3, multicenter, open-label, randomized clinical trials to evaluate the efficacy and safety of chemoimmunotherapy combinations involving atezolizumab.

A generalised semantic cognition account of aesthetic experience.

Given that aesthetic experiences typically involve extracting meaning from environment, we believe that semantic cognition research has much to offer the field of neuroaesthetics. In the current paper, we propose a generalised framework that is inspired by the semantic cognition literature and that treats aesthetic experience as just one example of how meaning accumulates. According to our framework, aesthetic experiences are underpinned by the same cognitive and brain systems that are involved in deriving meaning from the environment in general, such as modality-specific conceptual representations and controlled processes for retrieving the appropriate type of information.

Investigating the role of working memory resources across aesthetic and non-aesthetic judgements.

Aesthetic judgements dominate much of daily life by guiding how we evaluate objects, people, and experiences in our environment. One key question that remains unanswered is the extent to which more specialised or largely general cognitive resources support aesthetic judgements. To investigate this question in the context of working memory, we examined the extent to which a working memory load produces similar or different response time interference on aesthetic compared with non-aesthetic judgements.

IMpower150 Final Exploratory Analyses for Atezolizumab Plus Bevacizumab and Chemotherapy in Key NSCLC Patient Subgroups With EGFR Mutations or Metastases in the Liver or Brain.

Introduction: Final overall survival (OS) analyses are presented for EGFR mutations and liver or brain metastases subgroups in the phase 3 IMpower150 study (NCT02366143) evaluating atezolizumab plus bevacizumab plus carboplatin and paclitaxel (ABCP) or atezolizumab plus carboplatin and paclitaxel (ACP) versus bevacizumab plus carboplatin and paclitaxel (BCP).

Methods: Overall, 1202 patients (intention-to-treat population) with chemotherapy-naive, metastatic, nonsquamous NSCLC were randomized to ABCP, ACP, or BCP. Patients with treated, stable brain metastases were permitted.

Functional specificity and neural integration in the aesthetic appreciation of artworks with implied motion.

Although there is growing interest in the neural foundations of aesthetic experience, it remains unclear how particular mental subsystems (e.g. perceptual, affective and cognitive) are involved in different types of aesthetic judgements.

Oncogene-specific differences in tumor mutational burden, PD-L1 expression, and outcomes from immunotherapy in non-small cell lung cancer.

Background: Non-small cell lung cancer (NSCLC) patients bearing targetable oncogene alterations typically derive limited benefit from immune checkpoint blockade (ICB), which has been attributed to low tumor mutation burden (TMB) and/or PD-L1 levels. We investigated oncogene-specific differences in these markers and clinical outcome.

Methods: Three cohorts of NSCLC patients with oncogene alterations (n=4189 total) were analyzed.

An age-wise comparison of human airway smooth muscle proliferative capacity.

We compared the proliferation of neonatal and adult airway smooth muscle cells (ASMC) with no/moderate lung disease, in glucose- (energy production by glycolysis) or glucose-free medium (ATP production from mitochondrial oxidative phosphorylations only), in response to 10% fetal calf serum (FCS) and PDGF-AA. In the presence of glucose, cell counts were significantly greater in neonatal vs. adult ASMC.

Pooled analysis of clinical outcome for EGFR TKI-treated patients with EGFR mutation-positive NSCLC.

Patients with non-small-cell lung cancer (NSCLC) appear to gain particular benefit from treatment with epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKI) if their disease tests positive for EGFR activating mutations. Recently, several large, controlled, phase III studies have been published in NSCLC patients with EGFR mutation-positive tumours. Given the increased patient dataset now available, a comprehensive literature search for EGFR TKIs or chemotherapy in EGFR mutation-positive NSCLC was undertaken to update the results of a previously published pooled analysis.

Protease activated receptor-2 expression and function in asthmatic bronchial smooth muscle.

Asthmatic bronchial smooth muscle (BSM) is characterized by structural remodeling associated with mast cell infiltration displaying features of chronic degranulation. Mast cell-derived tryptase can activate protease activated receptor type-2 (PAR-2) of BSM cells. The aims of the present study were (i) to evaluate the expression of PAR-2 in both asthmatic and non asthmatic BSM cells and, (ii) to analyze the effect of prolonged stimulation of PAR-2 in asthmatic BSM cells on cell signaling and proliferation.

Evaluation of EGFR protein expression by immunohistochemistry using H-score and the magnification rule: re-analysis of the SATURN study.

Introduction: The phase III SATURN study demonstrated that first-line maintenance erlotinib extended progression-free survival (PFS) and overall survival (OS) versus placebo in patients with advanced non-small cell lung cancer (NSCLC). Analysis of epidermal growth factor receptor (EGFR) expression by immunohistochemistry (IHC) found no significant interaction between EGFR IHC status and PFS (p = 0.63) or OS (p = 0.

Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT-2): a randomised, double-blind trial.

Background: The results of FASTACT, a randomised, placebo-controlled, phase 2 study, showed that intercalated chemotherapy and erlotinib significantly prolonged progression-free survival (PFS) in patients with advanced non-small-cell lung cancer. We undertook FASTACT-2, a phase 3 study in a similar patient population.

Methods: In this phase 3 trial, patients with untreated stage IIIB/IV non-small-cell lung cancer were randomly assigned in a 1:1 ratio by use of an interactive internet response system with minimisation algorithm (stratified by disease stage, tumour histology, smoking status, and chemotherapy regimen) to receive six cycles of gemcitabine (1250 mg/m(2) on days 1 and 8, intravenously) plus platinum (carboplatin 5 × area under the curve or cisplatin 75 mg/m(2) on day 1, intravenously) with intercalated erlotinib (150 mg/day on days 15-28, orally; chemotherapy plus erlotinib) or placebo orally (chemotherapy plus placebo) every 4 weeks.

Role of YKL-40 in bronchial smooth muscle remodeling in asthma.

Rationale: Bronchial remodeling, including increased bronchial smooth muscle (BSM) mass, contributes to bronchial obstruction in asthma. However, its mechanisms are complex and remain controversial. Recently, a role of the chitinase 3-like 1 protein (YKL-40) has been evoked in asthma.

The pivotal role of airway smooth muscle in asthma pathophysiology.

Asthma is characterized by the association of airway hyperresponsiveness (AHR), inflammation, and remodelling. The aim of the present article is to review the pivotal role of airway smooth muscle (ASM) in the pathophysiology of asthma. ASM is the main effector of AHR.

[Pathophysiology of asthma].

Asthma pathophysiology involves bronchial hyperreactivity, inflammation and remodelling, these features being closely linked. Bronchial hyperreactivity is characterized by an excessive airway response to a wide range of stimuli. Bronchial inflammation is characterized by an infiltration of all layers of the bronchial wall by a variety of inflammatory cells, especially mast cells, lymphocytes and eosinophils.

Airway remodeling in asthma: new mechanisms and potential for pharmacological intervention.

The chronic inflammatory response within the airways of asthmatics is associated with structural changes termed airway remodeling. This remodeling process is a key feature of severe asthma. The 5-10% of patients with a severe form of the disease account for the higher morbidity and health costs related to asthma.

Control maintenance can be predicted by exhaled NO monitoring in asthmatic patients.

Background: Fractional exhaled nitric oxide (F(E)NO) is a marker of airway inflammation in asthma. Monitoring of such inflammation is currently not included in asthma guidelines and remains controversial. The hypothesis underlying the present study was that, F(E)NO could help assessing asthma control and, therefore, improve its management, by predicting loss of control in asthmatics.

Pathophysiology of bronchial smooth muscle remodelling in asthma.

Whereas the role of bronchial smooth muscle remains controversial in healthy subjects its role is well established in asthmatics. Bronchial smooth muscle contraction induces airway narrowing. The smooth muscle also contributes to bronchial inflammation by secreting a range of inflammatory mediators, recruiting and activating inflammatory cells, such as mast cells or T-lymphocytes.

[Magnetic liquid influence upon some plant species of pharmaceutical interest].

It was accomplished a study on the influence of a petroleum magnetic liquid upon two plant species of pharmaceutical interest: Papaver somniferum L. and Chelidonium majus L. Experimental observation aimed: callus accumulation, seed germination, mitotic index and fluorescence of the photosynthesis pigments.

[Cytogenetic changes induced by low-intensity microwaves in the species Triticum aestivum].

Seeds of Triticum aestivum having an uniform genophond have been exposed to a microwave flow, with a frequency of 9.75 GHz and a low intensity. The effects of microwaves at various doses on mitotic activity have been followed.

Validated assay for the quantification of anastrozole in human plasma by capillary gas chromatography-63Ni electron capture detection.

An assay was developed for the quantification of anastrozole [2,2'-[5-(1H-1,2,4-triazol-1-ymethyl)-1,3-phenylene]bis(2-++ +methylpropiononitrile)] in human plasma using liquid-liquid extraction. Anastrozole and an internal standard were chromatographed and detected by gas chromatography with electron capture detection, using a combination temperature-pressure program. The range of the assay is 3 to 100 ng/ml.