Multiple immune-related adverse events secondary to checkpoint inhibitor therapy in patients with advanced cancer: association with treatment effectiveness.

Introduction: Checkpoint inhibitors (CPI) are widely used in cancer treatment with a potential of causing immune-related adverse events (IRAEs). Several studies have reported a positive correlation between development of IRAEs and improved survival outcome. However, few studies have focused on the potential role of multiple IRAEs on treatment effectiveness. This study aimed at investigating the association between multiple IRAEs and treatment effectiveness in terms of progression-free survival (PFS) and overall survival (OS) in advanced cancer patients. Methods: We performed a retrospective cohort study at three Swedish centers. All patients (n=600) treated with PD-L1 or PD-1 inhibitor, in monotherapy or in combination for advanced cancer between January 2017 and December 2021 were included. Multiple IRAEs were defined as IRAEs involving more than one organ system either simultaneously or sequentially. Time-depending Cox-regression model to mitigate the risk for immortal time bias (ITB) was applied. Results: The major tumor types were non-small cell lung cancer (205 patients; 34.2%) and malignant melanoma (196 patients; 32.7%). Of all patients,32.8% developed single IRAE and 16.2% multiple IRAEs. Patients with multiple IRAEs showed significantly improved PFS (Hazard Ratio, HR=0.78 95% Confidence Interval, CI: 0.57-0.98) and OS (HR=0.65 95% CI: 0.44-0.95) compared to patients with single IRAE or no IRAE (HR=0.46 95% CI:0.34-0.62 for PFS vs HR=0.41 95% CI: 0.28-0.60 for OS). Conclusion: In conclusion, our data supports a stronger association between development of multiple as opposed to single IRAEs and clinical effectiveness in advanced cancer patients treated with CPIs.

Emerging contaminants: A One Health perspective.

Environmental pollution is escalating due to rapid global development that often prioritizes human needs over planetary health. Despite global efforts to mitigate legacy pollutants, the continuous introduction of new substances remains a major threat to both people and the planet. In response, global initiatives are focusing on risk assessment and regulation of emerging contaminants, as demonstrated by the ongoing efforts to establish the UN's Intergovernmental Science-Policy Panel on Chemicals, Waste, and Pollution Prevention. This review identifies the sources and impacts of emerging contaminants on planetary health, emphasizing the importance of adopting a One Health approach. Strategies for monitoring and addressing these pollutants are discussed, underscoring the need for robust and socially equitable environmental policies at both regional and international levels. Urgent actions are needed to transition toward sustainable pollution management practices to safeguard our planet for future generations.

Biochar affects compressive strength of Portland cement composites: a meta-analysis.

One strategy to reduce CO2 emissions from cement production is to reduce the amount of Portland cement produced by replacing it with supplementary cementitious materials (SCMs). Biochar is a potential SCM that is an eco-friendly and stable porous pyrolytic material. However, the effects of biochar addition on the performances of Portland cement composites are not fully understood. This meta-analysis investigated the impact of biochar addition on the 7- and 28-day compressive strength of Portland cement composites based on 606 paired observations. Biochar feedstock type, pyrolysis conditions, pre-treatments and modifications, biochar dosage, and curing type all influenced the compressive strength of Portland cement composites. Biochars obtained from plant-based feedstocks (except rice and hardwood) improved the 28-day compressive strength of Portland cement composites by 3-13%. Biochars produced at pyrolysis temperatures higher than 450 °C, with a heating rate of around 10 C min-1, increased the 28-day compressive strength more effectively. Furthermore, the addition of biochar with small particle sizes increased the compressive strength of Portland cement composites by 2-7% compared to those without biochar addition. Biochar dosage of < 2.5% of the binder weight enhanced both compressive strengths, and common curing methods maintained the effect of biochar addition. However, when mixing the cement, adding fine and coarse aggregates such as sand and gravel affects the concrete and mortar's compressive strength, diminishing the effect of biochar addition and making the biochar effect nonsignificant. We concluded that appropriate biochar addition could maintain or enhance the mechanical performance of Portland cement composites, and future research should explore the mechanisms of biochar effects on the performance of cement composites. Supplementary Information: The online version contains supplementary material available at 10.1007/s42773-024-00309-2.

The role of dacarbazine and temozolomide therapy after treatment with immune checkpoint inhibitors in malignant melanoma patients: A case series and meta-analysis.

Dacarbazine (DTIC) and its oral counterpart temozolomide (TMZ) have been the most used agents in advanced malignant melanoma (MM) patients and they are still used routinely. The preferred first line treatment, immune checkpoint inhibitors (CPIs) might shape the tumor and the tumor microenvironment, possibly affecting the response to subsequent therapies. The aim of this study was to investigate the treatment effect of DTIC/TMZ in MM patients after CPI therapy in a consecutive patient cohort and through systematic literature review and meta-analysis. Thirty-five patients with advanced MM treated with DTIC/TMZ after previous CPI therapy in three Swedish regions between 2017 and 2021 were recognized and seven case series studies were identified through systematic database review. Pooled data from all 345 patients showed a median real-world progression-free survival (rwPFS) of 1.9 months and overall survival (OS) of 6.0 months. Three of these studies were included in a meta-analysis comparing DTIC/TMZ after CPI treatment, versus no previous immunotherapy, showing no statistically significant differences in rwPFS or OS but higher real-world response rate to chemotherapy for the prior-CPI treated group (Odds Ratio: 2.24; 95% Confidence Interval: 1.04-4.86). The current study supports consideration of DTIC/TMZ in later line of treatment in the immunotherapy era.

Biochar and soil properties affect remediation of Zn contamination by biochar: A global meta-analysis.

Zinc (Zn) is one of the most common heavy metals that pollute soils and can threaten both environmental and human health. Biochar is a potential solution for remediating soil Zn contamination. This meta-analysis investigates the effect of biochar application on the remediation of Zn-contaminated soils and the factors affecting the remediation efficiency. We found that biochar application in Zn-contaminated soils reduced Zn bioavailability by up to 77.2% in urban soils, 55.1% in acidic soils, and 50.8% in coarse textured soils. Moreover, the remediation efficiency depends on the biochar production condition, with crop straw and sewage sludge feedstocks, high pyrolysis temperature (450-550 °C), low heating rate (<10 °C min-1), and short residence time (<180 min) producing high performing biochars. Biochar affects soil Zn bioavailability by changing soil pH and organic carbon, as well as through its high surface area, ash content, and O-containing surface functional groups. Our findings highlight the role of biochar as a promising and environmentally friendly material for remediating Zn contamination in acidic and/or coarse textured soils. We conclude that soil properties must be considered when selecting biochars for remediating soil Zn contamination.

Biochar modulating soil biological health: A review.

Biochar can be used for multifunctional applications including the improvement of soil health and carbon storage, remediation of contaminated soil and water resources, mitigation of greenhouse gas emissions and odorous compounds, and feed supplementation to improve animal health. A healthy soil preserves microbial biodiversity that is effective in supressing plant pathogens and pests, recycling nutrients for plant growth, promoting positive symbiotic associations with plant roots, improving soil structure to supply water and nutrients, and ultimately enhancing soil productivity and plant growth. As a soil amendment, biochar assures soil biological health through different processes. First, biochar supports habitats for microorganisms due to its porous nature and by promoting the formation of stable soil micro-aggregates. Biochar also serves as a carbon and nutrient source. Biochar alters soil physical and chemical properties, creating optimum soil conditions for microbial diversity. Biochar can also immobilize soil pollutants and reduce their bioavailability that would otherwise inhibit microbial growth. However, depending on the pyrolysis settings and feedstock resources, biochar can be comprised of contaminants including polycyclic aromatic hydrocarbons and potentially toxic elements that can inhibit microbial activity, thereby impacting soil health.