Anti-programmed death ligand 1 immunotherapies in cancer patients with pre-existing systemic sclerosis: A postmarketed phase IV safety assessment study.

OBJECTIVES: Cancer patients with pre-existing autoimmune disease, such as systemic sclerosis (SSc), are excluded from clinical trials, so the data on tolerability and efficacy of immune checkpoint inhibitors in these patients are limited. This study investigated the tolerability and efficacy of anti-programmed death ligand 1 (PD (L)1) immunotherapies in patients with pre-existing SSc. METHODS: Scleronco-01 was a multicentre, nationwide, open-label, phase IV observational study, from 2019 to 2021. RESULTS: Seventeen SSc patients receiving treatment for lung carcinoma (n = 13, 77%), head and neck cancer (n = 2, 12%), melanoma (n = 1, 6%), and colorectal carcinoma (n = 1, 6%) were included. The median (interquartile range) patient age was 60 (34-82) years. Fifteen (88%) patients received anti-PD1 (nivolumab and pembrolizumab) and two (12%) anti-PD-L1 (durvalumab). The median follow-up duration was 12 (range, 2-38) months. Four patients (24%) experienced flare-up of SSc symptoms. Ten patients (59%) developed an immune-related adverse event (grade I-II in 11 patients [65%], grade III-IV in one [6%]) without grade V. The overall response rate was 41% (7/17 patients). The median overall survival was 15.8 (95% confidence interval: 7.3 to not reached) months. CONCLUSION: Anti-PD1 or PD-L1 immunotherapies are suitable options for cancer patients with pre-existing SSc. Longer follow-up periods are required for long-term safety analyses.

Characteristics of Adult Patients with Idiopathic Retroperitoneal Fibrosis and Assessment of Risk of Relapse at Diagnosis.

OBJECTIVES: To compare adult patients' characteristics suffering from idiopathic retroperitoneal fibrosis between "relapse-free" and relapsing patients at the diagnosis and identify factors associated with relapse at initial presentation. METHODS: We conducted a retrospective multicentric study in four hospitals in Eastern France, from 1993 to 2020, of adult patients suffering from idiopathic retroperitoneal fibrosis. We analyzed clinical, biological, and radiological features at diagnosis and during a forty-month follow-up. RESULTS: Of 47 patients suffering from retroperitoneal fibrosis, 21 patients had idiopathic retroperitoneal fibrosis. Among them, 13 experienced one or more relapses during follow-up. At diagnosis, clinical characteristics, relevant comorbidities, biological and radiological features were similar between groups. Smoking cessation seems associated with decreased relapse risk (p: 0.0624). A total of 8 patients developed chronic renal failure during follow-up. Ureteral infiltration at diagnosis was associated with evolution to chronic renal failure (p: 0.0091). CONCLUSION: No clinical, biological, or radiological features could predict relapse at retroperitoneal fibrosis diagnosis, but smoking cessation may prevent relapse.

Towards Win-Win Policies for Healthy and Sustainable Diets in Switzerland.

The first Swiss national dietary survey (MenuCH) was used to screen disease burdens and greenhouse gas emissions (GHG) of Swiss diets (vegan, vegetarian, gluten-free, slimming), with a focus on gender and education level. The Health Nutritional Index (HENI), a novel disease burden-based nutritional index built on the Global Burden of Disease studies, was used to indicate healthiness using comparable, relative disease burden scores. Low whole grain consumption and high processed meat consumption are priority risk factors. Non-processed red meat and dairy make a nearly negligible contribution to disease burden scores, yet are key drivers of diet-related GHGs. Swiss diets, including vegetarian, ranged between 1.1-2.6 tons of CO2e/person/year, above the Swiss federal recommendation 0.6 ton CO2e/person/year for all consumption categories. This suggests that only changing food consumption practices will not suffice towards achieving carbon reduction targets: Systemic changes to food provisioning processes are also necessary. Finally, men with higher education had the highest dietary GHG emissions per gram of food, and the highest disease burden scores. Win-win policies to improve health and sustainability of Swiss diets would increase whole grain consumption for all, and decrease alcohol and processed meat consumption especially for men of higher education levels.

Characterizing the burden of disease of particulate matter for life cycle impact assessment.

Fine particulate air pollution (PM2.5) is a major environmental contributor to human burden of disease and therefore an important component of life cycle impact assessments. An accurate PM2.5 characterization factor, i.e., the impact per kg of PM2.5 emitted, is critical to estimating "cradle-to-grave" human health impacts of products and processes. We developed and assessed new characterization factors (disability-adjusted life years (DALY)/kgPM2.5 emitted), or the products of dose-response factors (deaths/kgPM2.5 inhaled), severity factors (DALY/death) and intake fractions (kgPM2.5 inhaled/kgPM2.5 emitted). In contrast to previous health burden estimates, we calculated age-specific concentration- and dose-response factors using baseline data, from 63 U.S. metropolitan areas, consistent with the U.S. study population used to derive the relative risk. We also calculated severity factors using 2010 Global Burden of Disease data. Multiplying the revised PM2.5 dose-responses, severity factors and intake fractions yielded new PM2.5 characterization factors that are higher than previous factors for primary PM2.5 but lower for secondary PM2.5 due to NOx. Multiplying the concentration-response and severity factors by 2005 ambient PM2.5 concentrations yielded an annual U.S. burden of 2,000,000 DALY, slightly lower than previous U.S. estimates. The annual U.S. health burden estimated from PM emissions and characterization factors was 2.2 times higher.

Life cycle-based water assessment of a hand dishwashing product: opportunities and limitations.

It is only recently that life cycle-based indicators have been used to evaluate products from a water use impact perspective. The applicability of some of these methods has been primarily demonstrated on agricultural materials or products, because irrigation requirements in food production can be water-intensive. In view of an increasing interest on life cycle-based water indicators from different products, we ran a study on a hand dishwashing product. A number of water assessment methods were applied with the purpose of identifying both product improvement opportunities, as well as understanding the potential for underlying database and methodological improvements. The study covered the entire life cycle of the product and focused on environmental issues related to water use, looking in-depth at inventory, midpoint, and endpoint methods. "Traditional" water emission driven methods, such as freshwater eutrophication, were excluded from the analysis. The use of a single formula with the same global supply chain, manufactured in 1 location was evaluated in 2 countries with different water scarcity conditions. The study shows differences ranging up to 4 orders in magnitude for indicators with similar units associated with different water use types (inventory methods) and different cause-effect chain models (midpoint and endpoint impact categories). No uncertainty information was available on the impact assessment methods, whereas uncertainty from stochastic variability was not available at the time of study. For the majority of the indicators studied, the contribution from the consumer use stage is the most important (>90%), driven by both direct water use (dishwashing process) as well as indirect water use (electricity generation to heat the water). Creating consumer awareness on how the product is used, particularly in water-scarce areas, is the largest improvement opportunity for a hand dishwashing product. However, spatial differentiation in the inventory and impact assessment model may lead to very different results for the product used under exactly the same consumer use conditions, making the communication of results a real challenge. From a practitioner's perspective, the data collection step in relation to the goal and scope of the study sets high requirements for both foreground and background data. In particular, databases covering a broad spectrum of inventory data with spatially differentiated water use information are lacking. For some impact methods, it is unknown as to whether or not characterization factors should be spatially differentiated, which creates uncertainty in their interpretation and applicability. Finally, broad application of life cycle-based water assessment will require further development of commercial life cycle assessment software.

Intake fraction for particulate matter: recommendations for life cycle impact assessment.

Particulate matter (PM) is a significant contributor to death and disease globally. This paper summarizes the work of an international expert group on the integration of human exposure to PM into life cycle impact assessment (LCIA), within the UNEP/SETAC Life Cycle Initiative. We review literature-derived intake fraction values (the fraction of emissions that are inhaled), based on emission release height and "archetypal" environment (indoor versus outdoor; urban, rural, or remote locations). Recommended intake fraction values are provided for primary PM(10-2.5) (coarse particles), primary PM(2.5) (fine particles), and secondary PM(2.5) from SO(2), NO(x), and NH(3). Intake fraction values vary by orders of magnitude among conditions considered. For outdoor primary PM(2.5), representative intake fraction values (units: milligrams inhaled per kilogram emitted) for urban, rural, and remote areas, respectively, are 44, 3.8, and 0.1 for ground-level emissions, versus 26, 2.6, and 0.1 for an emission-weighted stack height. For outdoor secondary PM, source location and source characteristics typically have only a minor influence on the magnitude of the intake fraction (exception: intake fraction values can be an order of magnitude lower for remote-location emission than for other locations). Outdoor secondary PM(2.5) intake fractions averaged over respective locations and stack heights are 0.89 (from SO(2)), 0.18 (NO(x)), and 1.7 (NH(3)). Estimated average intake fractions are greater for primary PM(10-2.5) than for primary PM(2.5) (21 versus 15), owing in part to differences in average emission height (lower, and therefore closer to people, for PM(10-2.5) than PM(2.5)). For indoor emissions, typical intake fraction values are ∼1000-7000. This paper aims to provide as complete and consistent an archetype framework as possible, given current understanding of each pollutant. Values presented here facilitate incorporating regional impacts into LCIA for human health damage from PM.