Checkpoint inhibitor pneumonitis (CIP) is an immunerelated adverse event that can occur after initiation of anti-programmed death 1/programmed death ligand 1 immune checkpoint inhibitor (ICI) therapy for the treatment of multiple malignancies, including NSCLC. However, the incidence of CIP has not been previously examined in a population that included both trial-enrolled and non-trialenrolled patients with advanced NSCLC. Furthermore, risk factors and other clinical characteristics associated with CIP severity are not known. In this study, we retrospectively examined clinical characteristics, incidence, and risk factors for CIP in a cohort of 205 patients with NSCLC, all of whom received anti-programmed death 1/programmed death ligand 1 ICIs. Our results demonstrate a higher incidence of CIP (19%) than previously reported in clinical trials (3%-5%). Our data also suggest that tumor histologic type may be a risk factor for CIP development. We observed a wide range of time to onset of CIP (median 82 days), with high morbidity and mortality associated with higher-grade CIP regardless of degree of immunosuppression. Our data provide new insight into the epidemiology and clinical
Immune checkpoint inhibitors (ICIs) are newer, immunotherapy-based drugs that have been shown to improve survival in advanced non-small cell lung cancer (NSCLC). Unlike traditional chemotherapeutic agents, ICIs work by boosting the body's natural tumor killing response.However, this unique mechanism of action has also led to the recognition of class-specific side effects. Labeled immune-related adverse events, these toxicities can affect multiple organ systems including the lungs. Immune-mediated lung injury because of ICI use, termed checkpoint inhibitor pneumonitis (CIP), occurs in about 3% to 5% of patients receiving ICIs; however, the real-world incidence of this entity may be higher, especially now that ICIs are being used in nonclinical trial settings. In this review, we briefly introduce the biology of ICIs and the indications for ICI use in NSCLC and then discuss the epidemiology and clinical and radiologic manifestations of CIP. Next, we discuss management strategies for CIP, including the current consensus on management of steroid-refractory CIP. Given the nascent nature of this field, we highlight areas of uncertainty and emerging research questions in the burgeoning field of checkpoint inhibitor pulmonary toxicity.
Implantation of occlusion devices is an effective approach for the treatment of congenital heart diseases in the clinic. However, most commercial clinical occlusion devices are currently made of nondegradable metals, which may lead to complications such as perforation, allergies, and erosion. In this work, 4D-printed novel, biodegradable, remotely controllable, and personalized shape memory occlusion devices are demonstrated and atrial septal defect occluders are exemplified. By incorporating Fe 3 O 4 magnetic particles into the shape memory poly(lactic acid) matrix, the deployment of the occluders can be controlled remotely after implantation. The excellent cytocompatibility and histocompatibility are conducive to cell adhesion and ingrowth of granulation tissues into the occluders, thus facilitating rapid endothelialization. In addition, personalized shape memory occluders ensure an ideal fit and provide sufficient support for defects. Therefore, 4D-printed shape memory occluders can be used as a potential substitute for metal occlusion devices.
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