Effect of excess weight and immune-related adverse events on the efficacy of cancer immunotherapy with anti-PD-1 antibodies

Immunotherapy is an effective treatment in advanced cancer, although predictors of response are limited. We studied whether excess weight influences the efficacy outcomes of immunotherapy. We have also evaluated the combined prognostic effect of excess weight and immune-related adverse events (irAEs). Efficacy of anti-PD-1 treatment was evaluated with both objective radiological response (ORR) rate and progression-free survival (PFS), and toxicity with irAEs. We studied the association between excess weight and ORR, PFS or irAEs. 132 patients diagnosed with advanced cancer were included. Median body mass index (BMI) was 24.9 kg/m2. 64 patients had normal weight (BMI<25 kg/m2), and 64 patients had excess weight (BMI≥25 kg/m2). Four patients had underweight and were excluded from further analysis. ORR was achieved in 50 patients (38.0%), median PFS was 6 months. 44 patients developed irAEs (33.3%). ORR was higher in excess weight patients than in patients with normal weight (51.6% vs 25.0%; OR 3.45, p = .0009). PFS was improved in patients with excess weight (7.25 months vs 4 months, HR 1.72, p = .01). The incidence of IrAEs was not different in patients with excess weight (54.5% vs 43.2%, p = .21). When high BMI and irAEs were combined, we observed a marked prognostic trend in ORR rate (87.5% vs 6.2%; OR 161.0, p < .00001), and in PFS (14 months vs 3 months; HR 5.89, p < .0001). Excess weight patients with advanced cancer that receive single-agent anti-PD-1 antibody therapy exhibit a significantly improved clinical outcome compared with normal BMI patients. This association was especially marked when BMI and irAEs were considered combined.This study was funded in part by the project Discovery, Validation and Implementation of Biomarkers for Precision Oncology [PIE15/00068], and the project FIS PI17/01865 from the Instituto de Salud Carlos III, Ministerio de Economia y Competitividad, awarded to RC, and the projects [JR 17/00007 and PI17/008], awarded to NRL

Temperature Effects Explain Continental Scale Distribution of Cyanobacterial Toxins

Insight into how environmental change determines the production and distribution of cyanobacterial toxins is necessary for risk assessment. Management guidelines currently focus on hepatotoxins (microcystins). Increasing attention is given to other classes, such as neurotoxins (e.g., anatoxin-a) and cytotoxins (e.g., cylindrospermopsin) due to their potency. Most studies examine the relationship between individual toxin variants and environmental factors, such as nutrients, temperature and light. In summer 2015, we collected samples across Europe to investigate the effect of nutrient and temperature gradients on the variability of toxin production at a continental scale. Direct and indirect effects of temperature were the main drivers of the spatial distribution in the toxins produced by the cyanobacterial community, the toxin concentrations and toxin quota. Generalized linear models showed that a Toxin Diversity Index (TDI) increased with latitude, while it decreased with water stability. Increases in TDI were explained through a significant increase in toxin variants such as MC-YR, anatoxin and cylindrospermopsin, accompanied by a decreasing presence of MC-LR. While global warming continues, the direct and indirect effects of increased lake temperatures will drive changes in the distribution of cyanobacterial toxins in Europe, potentially promoting selection of a few highly toxic species or strains.Peer reviewe

Erratum: Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

Interpretation: By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Flujos de capitales, choques externos y respuestas de política en países emergentes

Las crisis financieras recientes han incrementado de manera significativa la complejidad de la política económica. Hoy día es necesario estar preparado para enfrentar huracanes financieros que surgen de lugares inesperados y que se expanden alrededor del mundo como reguero de pólvora. Para peor, estas crisis producen un profundo desconcierto entre inversores y analistas —incluyendo al propio Fondo Monetario Internacional—. La presente obra contiene un conjunto importante de artículos de alto calibre profesional que se enfocan sobre los nuevos desafíos que enfrenta la política económica en estas circunstancias. Los artículos estudian las características de los flujos de capitales, tanto en su totalidad como en su composición (capital de cartera, inversión directa, etc.) y su interrelación con el mercado de commodities (café y petróleo, en particular). Esto se complementa con un estudio cuidadoso de las vulnerabilidades financieras y un detallado análisis del papel de todos estos factores en la economía colombiana. El libro se convierte en un verdadero pionero en esta literatura y debería transformarse en referencia obligada para todos aquellos que quieran entender los nuevos fenómenos y desarrollar herramientas para prevenir sus peores consecuencias o paliar sus costos en economías emergentes, como la colombiana

Stratification strength and light climate explain variation in chlorophyll a at the continental scale in a European multilake survey in a heatwave summer

To determine the drivers of phytoplankton biomass, we collected standardized morphometric, physical, and biological data in 230 lakes across the Mediterranean, Continental, and Boreal climatic zones of the European continent. Multilinear regression models tested on this snapshot of mostly eutrophic lakes (median total phosphorus [TP] = 0.06 and total nitrogen [TN] = 0.7 mg L-1), and its subsets (2 depth types and 3 climatic zones), show that light climate and stratification strength were the most significant explanatory variables for chlorophyll a (Chl a) variance. TN was a significant predictor for phytoplankton biomass for shallow and continental lakes, while TP never appeared as an explanatory variable, suggesting that under high TP, light, which partially controls stratification strength, becomes limiting for phytoplankton development. Mediterranean lakes were the warmest yet most weakly stratified and had significantly less Chl a than Boreal lakes, where the temperature anomaly from the long-term average, during a summer heatwave was the highest (+4 degrees C) and showed a significant, exponential relationship with stratification strength. This European survey represents a summer snapshot of phytoplankton biomass and its drivers, and lends support that light and stratification metrics, which are both affected by climate change, are better predictors for phytoplankton biomass in nutrient-rich lakes than nutrient concentrations and surface temperature.Peer reviewe

Stratification strength and light climate explain variation in chlorophyll a at the continental scale in a European multilake survey in a heatwave summer

To determine the drivers of phytoplankton biomass, we collected standardized morphometric, physical, and biological data in 230 lakes across the Mediterranean, Continental, and Boreal climatic zones of the European continent. Multilinear regression models tested on this snapshot of mostly eutrophic lakes (median total phosphorus [TP] = 0.06 and total nitrogen [TN] = 0.7 mg L−1), and its subsets (2 depth types and 3 climatic zones), show that light climate and stratification strength were the most significant explanatory variables for chlorophyll a (Chl a) variance. TN was a significant predictor for phytoplankton biomass for shallow and continental lakes, while TP never appeared as an explanatory variable, suggesting that under high TP, light, which partially controls stratification strength, becomes limiting for phytoplankton development. Mediterranean lakes were the warmest yet most weakly stratified and had significantly less Chl a than Boreal lakes, where the temperature anomaly from the long-term average, during a summer heatwave was the highest (+4°C) and showed a significant, exponential relationship with stratification strength. This European survey represents a summer snapshot of phytoplankton biomass and its drivers, and lends support that light and stratification metrics, which are both affected by climate change, are better predictors for phytoplankton biomass in nutrient-rich lakes than nutrient concentrations and surface temperature

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population