Pan-immune-inflammation and its dynamics: predictors of survival and immune-related adverse events in patients with advanced NSCLC receiving immunotherapy

Abstract Objectives Pan-immune-inflammation value (PIV) is defined by the neutrophil, platelet, monocyte, and lymphocyte counts and is associated with immune-checkpoint inhibitor (ICI) therapy outcomes in advanced non-small cell lung cancer (aNSCLC). However, PIV is dynamic under therapy and its longitudinal assessment may help predict efficacy. This study investigated the impact of baseline PIV and its dynamics on ICI efficacy and its immune-related adverse events (irAEs). The study additionally attempted to understand the biological significance of PIV. Patients and methods This retrospective study analyzed the clinical data of 269 consecutive patients with aNSCLC. PIV was calculated at baseline and at weeks 3–4 to determine its association with overall survival (OS), progression-free survival (PFS), and irAEs. Results Results revealed that low baseline PIV was positively correlated with the incidence of irAEs. Moreover, a low PIV at baseline was significantly associated with a prolonged PFS (median PFS: 10 vs. 7 months, p = 0.0005) and OS (median OS: 29 vs. 21 months, p < 0.0001). When the PIV at baseline and weeks 3–4 was considered together, its low dynamics correlated with a higher incidence of irAEs (p = 0.001), a longer PFS (median PFS, 9 vs. 6 months, p = 0.012), and a longer OS (median OS; 28 vs. 21 months, p = 0.002). Conclusion Thus, PIV at baseline and its dynamics are novel and potent predictors of irAEs, PFS, and OS in patients with aNSCLC receiving immunotherapy. Moreover, the PIV dynamics may be an effective, novel surrogate marker to dynamically observe the efficacy of immunotherapy

Theoretical Calculation of High-Pressure CO2 Jet under Composite Rock-Breaking Based on Span-Wagner Equation of State

Peer reviewedPostprin

Protecting Mobile Livelihoods: Actors’ Responses to the Emerging Health Challenges in Beijing and Tianjin

Drawing on extensive fieldwork in Beijing and Tianjin, and applying a livelihood framework combined with a well-being perspective, this article examines an important aspect of rural–urban migrants’ social protection in China, namely migrants’ health, in particular work safety and occupational health. It argues that migrant workers’ social rights to health and livelihoods are a fiercely contested domain of citizenship entailing aspects of exclusion, inclusion, and control and allocation of economic, social, and political resources. The article shows that in spite of the accelerated pace of legislation and consolidated efforts to reconstruct the welfare system in China in recent years, the new social security schemes have thus far, by and large, failed to protect migrant workers in a systematic manner. The issues raised in the article therefore call for greater academic attention and more effective public policy responses

Complete chloroplast genome of a high-quality forage in north China, Medicago ruthenica (Fabaceae：Trifolieae)

Medicago ruthenica is a well-known high-quality forage due to its good palatability and strong tolerance to drought, cold and saline-alkali stress. Here, the complete chloroplast genome sequence of M. ruthenica was reported. The chloroplast genome is 126,939 bp in length. This chloroplast genome has no inverted repeat (IR) regions, which is very common in the family Fabaceae. The M. ruthenica chloroplast genome encodes 107 genes, including 73 protein-coding genes, 30 tRNA genes, and 4 rRNA genes. Phylogenetic analysis result strongly suggested that M. ruthenica is a distinct lineage in Medicago, being sister to highly supported clade composed of three species (M. hybrida, M. papillosa and M. sativa)

Factors and Regional Differences Associated with Endometriosis: A Multi-Country, Case–Control Study

<p></p><p><strong>Article full text</strong></p> <p><br><br> The full text of this article can be found here. <a href="https://link.springer.com/article/10.1007/s12325-016-0366-x">https://link.springer.com/article/10.1007/s12325-016-0366-x</a></p><p></p><p></p><p> <br><br> <strong>Provide enhanced digital features for this article</strong><br> There are currently no enhanced digital features for this article. If you are an author of this publication and would like to provide additional enhanced digital features for your article then please contact [email protected].<br> <br><br> The journal offers a range of additional enhanced digital features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.<br> <br><br> Other enhanced features include, but are not limited to:</p><p> </p><p>• Summary Slides</p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p><br><p></p

Physiologically based pharmacokinetic modeling for predicting irinotecan exposure in human body

Colorectal cancer is the third leading cause of cancer-related deaths in the United States. Treatment of colorectal cancer remains a challenge to clinicians as well as drug developers. Irinotecan, a Camptothecin derivative, is successfully used for the treatment of this rapidly progressing malignancy and finds its place in the first line of therapeutic agents. Irinotecan is also effective in treating SCLC, malignant glioma and pancreatic adenocarcinoma. However, its adverse effects limit its clinical application. Mainly metabolized by hepatic route, and excreted through biliary tract, this dug has been found to possess high variation in patients in its pharmacokinetic (PK) profile. Physiologically based pharmacokinetic (PBPK) models using compartmental approach have attained their position to foresee the possible PK behavior of different drugs before their administration to patients and such models have been proposed for several anticancer agents. In this work, we used WB-PBPK technology to develop a model in a population of tumor patients who used IV irinotecan therapy. This model depicted the concentration of drug and its pharmacologically active metabolite in human body over a specific period of time. Knowledge about pharmacokinetic parameters is extracted from this profile and the model is evaluated by the observed results of clinical study presented in literature. The predicted behavior of the drug by this approach is in good agreement with the observed results and can aid in further exploration of PK of irinotecan in cancer patients, especially in those concomitantly suffer from other morbidity