Management, risk factors and prognostic impact of checkpoint-inhibitor pneumonitis (CIP) in lung cancer - A multicenter observational analysis.

INTRODUCTION: Checkpoint-inhibitor pneumonitis (CIP) represents a major immune-related adverse event (irAE) in patients with lung cancer. We aimed for the clinical characterization, diagnostics, risk factors, treatment and outcome in a large cohort of patients from everyday clinical practice. PATIENTS AND METHODS: For this retrospective analysis, 1,376 patients having received checkpoint inhibitors (CPI) in any line of therapy from June 2015 until February 2020 from three large-volume lung cancer centers in Berlin, Germany were included and analyzed. RESULTS: With a median follow-up of 35 months, all-grade, high-grade (CTCAE ≥ 3) and fatal CIP were observed in 83 (6.0%), 37 (2.7%) and 12 (0.9%) patients, respectively, with a median onset 4 months after initiation of CPI therapy. The most common radiologic patterns were organizing pneumonia (OP) and non-specific interstitial pneumonia (NSIP) (37% and 31%). All except 7 patients with G1-2 CIP interrupted treatment. Corticosteroids were administered to 74 patients with a median starting dose of 0.75 mg/kg. After complete restitution (n = 67), re-exposure to CPI (n = 14) led to additional irAE in 43% of the cases. Thoracic radiotherapy targeting the lung was the only independent risk factor for CIP (odds ratio 2.8, p < 0.001) and pretherapeutic diffusing capacity for carbon monoxide inversely correlated with CIP severity. Compared with patients without CIP and non-CIP irAE, CIP was associated with impaired overall survival (hazard ratios 1.23, p = 0.24 and 2.01, p = 0.005). CONCLUSIONS: High-grade CIP accounts for almost half of all CIP cases in an allcomer lung cancer population. A continuous vigilance, rapid diagnostics and adequate treatment are key to prevent disease progression associated with impaired survival.

Which qualities should built environment possess to ensure satisfaction of higher-education students with remote education during pandemics?

The COVID-19 pandemic has suddenly switched most education processes from face-to-face to remote mode, obliging millions of students to utilize their residences as study spaces. However, the characteristics of their residential built environments differ in terms of regional, social, cultural, and technological aspects. These differences should impact the students' performance and satisfaction which needs to be measured and studied. The present study aims to identify the effect of the residential built environment on students' satisfaction and academic performance during the COVID-19 pandemic. It was conducted in two countries, Kazakhstan (KZ) and Norway (NO), using a comprehensive online survey to gather data. An empirical assessment based on the structural equation model was employed to identify links between health, safety, and comfort of students' facilities and academic performance and satisfaction. We conclude that the built environment affects both satisfaction for remote education and their learning performance. Significant differences in readiness for remote education have been observed between urban and non-urban living areas: (1) The role of health-and-safety convenience seems to increase with the urbanization level of the respondents' living spaces; (2) in contrast, for non-urban residents, the provision of comfort facilities is dominant. In the meantime, an analysis "by regions" revealed that health-and-safety-related facilities in residences are more critical for remote education in Central Asia (KZ). In contrast, the comfort features of residences being more important for the students studying remotely in Northern Europe (NO). These results provide an understanding that would assist in improving remote education and preparing pandemic-ready living areas.

Synergistic effect of immobilized laminin and nerve growth factor on PC12 neurite outgrowth.

Immobilized extracellular matrix proteins and neurotrophins have been extensively studied to enhance neuronal adhesion and proliferation on surfaces for applications in nerve tissue engineering and neuroprosthetic devices. This article describes how the coimmobilization of laminin, an extracellular matrix protein and nerve growth factor (NGF), a neurotrophin can enhance neurite outgrowth observed separately with each type of molecule. In the absence of immobilized NGF, PC12 neurite outgrowth is influenced strongly by the presence of NGF in solution and unaffected by significant increases in laminin surface density (18.7-93.5 ng/mm(2)). However, when both laminin and NGF are immobilized together, the surface density of laminin is an important factor in determining whether or not the neurite outgrowth-promoting effect of NGF can be obtained. PC12 neurite outgrowth on surfaces with coimmobilized laminin and NGF with surface densities of 27.6 ng/mm(2) and 1.4 ng/mm(2), respectively, are similar to that observed on surfaces with immobilized laminin and dissolved NGF.