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The aim of this study was to reach a consensus on a set of proposals to optimise the disease management of Multiple myeloma (MM) within the Spanish National Health System (SNHS) and to apply the Social Return on Investment (SROI) method to estimate their social impact.A Multidisciplinary Working Team (MWT) including MM main stakeholders was organised. A survey was administered to gather information from patients regarding the impact of MM on different life domains. A forecast-type SROI analysis, with a 1-year timeframe, was applied.Fifteen proposals were selected, to optimise MM management, including actions for early diagnosis, psychological support, improvement of information for patients and quick access to palliative care, among others. The implementation of these proposals would benefit patients, their informal caregivers and the SNHS. The investment required would amount to 10.32 million euros with a social return of 43.31 million euros: 4.2 euros for each euro invested. According to the sensitivity analysis, this ratio could range from 3.38 to 5.20 euros from the worst to the best-case scenario.The current management of MM could be optimised by implementing a set of proposals that would most likely result in an overall positive social return.

Objective Early detection of patients with COVID-19 who will need mechanical invasive ventilation (MIV) may aid in delivering proper care and optimizing the use of limited resources. Methods In this single-center retrospective observational study, we aimed to identify simple laboratory parameters that in combination with ferritin (a surrogate marker of severe inflammation) may help predict early (first 48 hours) MIV. A total of 160 patients with COVID-19 in whom serum ferritin, absolute lymphocyte count (ALC), platelet count, C-reactive protein (CRP), and lactate dehydrogenase (LDH) had been analyzed at admission were included. Results We found that ferritin, LDH, ALC, and CRP predicted with 88% accuracy the probability of early MIV. Results indicated that LDH showed the greater area under the curve (AUC), with a value of 89.1%. Using the AUC, we established cutoff values for clinical application. Finally, we developed a classification tree based on LDH for its clinical use. Conclusion Ferritin, LDH, ALC, and CRP predict with 88% accuracy the probability of early MIV.

Microplastics (MPs) are emerging pollutants detected everywhere in the environment, with the potential to harm living organisms. The present study investigated the concentration, morphology, and composition of MPs, between 20 μm and 5 mm, in a drinking water treatment plant (DWTP) located close to Barcelona (Catalonia, NE Spain). The sampling included different units of the DWTP, from influent to effluent as well as sludge line. Sampling strategy, filtration, allows sampling of large volumes of water avoiding sample contamination, and during 8 h in order to increase the representativeness of MPs collected. The pre-treatment of the samples consisted of advanced oxidation with Fenton's reagent and hydrogen peroxide, followed by density separation of the particles with zinc chloride solution. Visual identification was performed with an optical and stereoscopic microscope with final Fourier-transform infrared spectroscopic (FTIR) confirmation. MPs were found in all DWTP samples, with concentrations from 4.23 ± 1.26 MPs/L to 0.075 ± 0.019 MPs/L in the influent and effluent of the plant, respectively. The overall removal efficiency of the plant was 98.3%. The most dominant morphology was fibers followed by fragments and films. Twenty-two different polymer types were identified and synthetic cellulose, polyester, polyamide, polypropylene, polyethylene, polyurethane, and polyacrylonitrile were the most common. Although MPs could be incorporated from the distribution network, MPs intake from drinking water from this DWTP was not an important route compared to fish and seafood ingestion.

Identification of dominant airborne Particulate Matter (PM) sources is essential for maintaining high air quality standards and thus ensuring a good public health. In this study, different approaches were applied for source apportionment of three PM fractions (PM1, PM2.5 and PM10) at the outdoor of 14 schools of a coastal city with a significant land use interweaving such as Tarragona (Spain). PM were collected in 24h-quartz microfiber filters in two seasonal campaigns (cold and warm), together with nine local potential sources, so a total of 84 samples were chemically, mineralogically, and isotopically characterised. Source apportionment was assessed by (i) main chemical components, (ii) Principal Component Analysis (PCA), (iii) dual C and N isotope approach, and (iv) a Bayesian isotope mixing model. When chemical concentrations were grouped into marine, crustal, secondary inorganic aerosols and organic matter + elemental carbon categories, the unaccounted component reached 45% of PM mass. The PCA allowed to identify also traffic and industrial contributions, reducing the unaccounted mass to about 25%. Adding δ13C and δ15N values, secondary organic aerosol could be estimated and a continuous contribution of diesel combustion was identified together with a remarkable use of natural gas in winter. Isotopic values were better understood when considering air masses back trajectories and a possible long-distance contribution from coal-fired electric generating units (EGUs). Finally, using Bayesian dual isotope mixing models, the unaccounted PM mass was reduced up to 5% when adding these EGUs to marine-carbonate related, road traffic, domestic heating, waste incinerator and livestock waste contributions. The added value of the dual isotope approach combined with a Bayesian isotope mixing model, in comparison with conventional chemical approaches, was thus demonstrated for PM source apportionment in an urban and industrial site where many sources and processes converge and can then be applied to other complex cities.

International audience; In 2016, the European Hematology Association (EHA) published the EHA Roadmap for European Hematology Research(1) aiming to highlight achievements in the diagnostics and treatment of blood disorders, and to better inform European policy makers and other stakeholders about the urgent clinical and scientific needs and priorities in the field of hematology. Each section was coordinated by 1-2 section editors who were leading international experts in the field. In the 5 years that have followed, advances in the field of hematology have been plentiful. As such, EHA is pleased to present an updated Research Roadmap, now including 11 sections, each of which will be published separately. The updated EHA Research Roadmap identifies the most urgent priorities in hematology research and clinical science, therefore supporting a more informed, focused, and ideally a more funded future for European Hematology Research. the 11 EHA Research Roadmap sections include normal hematopoiesis; malignant lymphoid diseases; malignant myeloid diseases; anemias and related diseases; platelet disorders; blood coagulation and hemostatic disorders; transfusion medicine; infections in hematology; hematopoietic stem cell transplantation; CAR-T and Other cell-based immune therapies; and gene therapy.

In 2016, total suspended particles (TSP) and fine particles (PM2.5) were collected near four e-waste recycling parks in a region of Southern China. TSP and PM2.5 levels and composition around these industrial activities were determined and the potential risks for human health due to the exposure to toxic elements contained on fine particles (PM2.5) were evaluated. Levels of TSP and PM2.5 were lower with advanced recycling methods than with small recycling e-waste workshops operating in the sampling region. The main trace elements in particles were Cu, Pb, and Ti, the same as those detected before the transition to advanced dismantling methods in e-waste recycling. Significantly higher levels of Cu, Pb, Sn, Te, Tl and NH4+ in TSP and Cu and Te in PM2.5 were found in e-waste recycling areas than in BG site. Taking Cu as the indicative element emitted from e-waste recycling activities, significant high positive correlations between Cu and W, and Cu and Te were found. These elements are present and can be released from electrical and electronical components during e-waste recycling processes. Exposure to elements for the population living near these e-waste recycling parks means carcinogenic risks above the acceptable threshold (>10-5).

A significant proportion of adult patients with acute myeloid leukemia (AML) fail to achieve complete remission or will relapse later on after achieving it. Prognosis for relapsed or refractory (R/R) AML patients remains discouraging, with the main curative option still relying on hematopoietic stem cell transplant (HSCT) for those who are eligible. Beyond morphological bone marrow and peripheral blood assessment, evaluation of patient performance status and comorbidities, as well as genetic/molecular characterization, is crucial to make an accurate diagnosis and prognosis, which will be useful to select the most appropriate treatment. Emerging strategies are mainly focusing on the development of immune- and molecular-based approaches. Novel targeted therapies are generally well tolerated, potentially allowing them to be administered alone or in combination with classical chemotherapy agents. Enrolment in clinical trials should be considered first option for R/R AML patients, either as a bridge to HSCT or to benefit from novel therapies that eventually may prolong survival and improve quality of life. An Iberian expert panel has reviewed the recent advances in the management of R/R AML with the aim to develop updated evidence and expert opinion-based recommendations.

Inhalation of particulate matter (PM) has been linked to serious adverse health effects, such as asthma, cardiovascular diseases and lung cancer. In the present study, coarse (PM10-2.5), accumulation mode (PM2.5-0.25), and quasi-ultrafine (PM0.25) particulates were collected inside twelve educative centers of Tarragona County (Catalonia, Spain) during two seasons (cold and warm). Chemical characterization of PM, as well as risk assessment were subsequently conducted in order to evaluate respiratory and digestive risks during school time for children. Levels and chemical composition of PM were very different among the 12 centers. Average PM levels were higher during the cold season, as well as the concentrations of most toxic metals. In most schools, PM levels were below the daily PM10 threshold established in the regulation (50 μg/m3), with the exception of school number 1 during the cold season. On average, and regardless of season, coarse PM was highly influenced by mineral matter, while organic matter and elemental carbon were prevalent in quasi-ultrafine PM. The concentrations of the toxic elements considered by the legislation (As, Cd, Pb, and Ni) were below their correspondent regulatory annual limits. Calculated risks were below the safety thresholds, being fine fractions (PM2.5-0.25 and PM0.25) the main contributors to both digestive and respiratory risks.

Microplastics (MPs) are accessible for organisms with active filter feeding strategies, as are many marine molluscs, which live attached or semi-buried in sediments. In the present study, MPs (from 0.02 to 5 mm) concentration, morphology, and composition were determined in consumed mollusc species of the Catalan coast (NW Mediterranean Sea). Microplastic concentrations, morphologic characteristics and composition were studied according to species, catchment zones and depuration condition. Finally, human intake of MPs through molluscs' consumption was determined.2300 individuals were analysed, being 1460 MPs extracted and their size, and polymeric composition registered. Big oysters and mussels showed the highest MPs concentration by individual, with levels of 22.8 ± 14.4 and 18.6 ± 23.0 MPs/individual, respectively. Mean annual MPs (≥20 μm) consumption for adult population was estimated in 8103 MPs/year, with a 95th percentile of 19,418 MPs/year. It suggests that the consumption of molluscs is an important route of MPs exposure for the Catalan population.

Mediterranean Sea has been proposed as the sixth greatest accumulation zone for marine litter and the most affected regarding to microplastics (MPs). Tarragona (Catalonia, NE Spain) coastal region suffers high pressure due to urbanization, tourism, industrial harbour and petrochemical/plastic industries. The present study aims to quantify and characterize in size, morphology and composition the MPs present in sandy beaches, marine sediments, and surface seawaters of Tarragona coastal region. MPs mean abundance were 1.30 items/m3 in surface seawaters, 32.4 items/kg in marine sediments, and 10.7 items/kg in sandy beaches. Polyester fibres were dominant MPs in bottom sediments and seawater meanwhile polyethylene and polypropylene fragments were the main MPs in beaches. The fibres balls associated with bottom sediments, organic matter and plankton were abundant, masking the real quantity of fibres in each reservoir. The abundance by volume of seawater MPs was higher to those found in oceanic areas and similar to other areas of Mediterranean Sea, corroborating that Western Mediterranean Sea as a region of MPs accumulation. MPs composition and abundance suggested the input of numerous land-base-sources, WWTP (wastewater treatment plants) effluents discharges, and emissaries as the most important. Marine MPs pollution were studied from an integrative point of view, that includes superficial sea water, sand from beaches and sediments. The dynamics of MPs in Tarragona coast were characterized by seawater as the media that receive and facilitate dispersion and fragmentation. The shoreline acts as an intermediate reservoir with constant weathering and active exchange with seawater surface and the sediments acts as a significant sink for medium MPs sizes. It is necessary to develop protocols and guidelines for MPs analysis to obtain harmonized and comparable results.

Air pollution by airborne particles is a serious health problem worldwide. The present study was aimed at investigating the concentrations and composition of total suspended particles (TSPs) and PM2.5 at various industrial/commercial sites of Guangzhou, a megacity of Southern China. Major and trace elements, ions and carbonaceous fraction were determined and main components were calculated. In addition, in order to assess the potential toxic on the respiratory system of these PM, cytotoxicity of size-fractionated particles (PM10-5.6, PM5.6-3.3, PM3.3-1.1, PM1.1-0.43) for a human lung cancer cell line (A549) was also investigated. Correlations between PM constituents and toxicity were assessed. Median levels of TSPs and PM2.5 in industrial/commercial sites were 206 and 57.7 μg/m3, respectively. Nickel, Cu, Mo, Mn, Pb, and Ti were the most abundant metals in TSPs and PM2.5. Industrial activities and coal combustion were the most important sources of carbonaceous particles in the zone. MTT assays showed that PM10-5.6 and PM1.1-0.43 had the highest and the lowest cytotoxicity to A549 cell lines, respectively. Inhalable particles around the manufacturing of metal facilities and formal waste treatment plants showed a high cytotoxicity to A549 cell lines. In general terms, no significant correlations were found between main components of PM and toxicity. However, W showed a significant correlation with cell viability.

Microalgae growth inhibition assays are candidates for referent ecotoxicology as a fundamental part of the strategy to reduce the use of fish and other animal models in aquatic toxicology. In the present work, the performance of Chlorella vulgaris exposed to heavy metals following standardized growth and photosynthesis inhibition assays was assessed in two different scenarios: (1) dilutions of single heavy metals and (2) an artificial mixture of heavy metals at similar levels as those found in natural rivers. Chemical speciation of heavy metals was estimated with Visual MINTEQ software, free heavy metal ion concentrations were used as input data, together with microalgae growth and photosynthesis inhibition, to compare different effects and explain possible toxicity mechanisms. The final goal was to assess the suitability of the ecotoxicological test based on the growth and photosynthesis inhibition of microalgae cultures, supported by mathematic models for regulatory and decision-making purposes. The C. vulgaris algae growth inhibition test was more sensitive for As, Zn, and Pb exposure whereas the photosynthesis inhibition test was more sensitive for Cu and Ni exposure. The effects on growth and photosynthesis were not related. C. vulgaris evidenced the formation of mucilaginous aggregations at lower copper concentrations. We found that the toxicity of a given heavy metal is not only determined by its chemical speciation, other chemical compounds (as nutrient loads) and biological interactions play an important role in the final toxicity. Predictive mixture effect models tend to overestimate the effects of metal mixtures in C. vulgaris for both growth and photosynthesis inhibition tests. Growth and photosynthesis inhibition tests give complementary information, and both are a fast, cheap, and sensitive alternative to animal testing. More research is needed to solve the challenge of complex pollutant mixtures as they are present in natural environments, where microalgae-based assays can be suitable monitoring tools for pollution management and regulatory purposes.

Concentrated human milk (HM-concentrate) can be obtained from the simple and inexpensive method of donated breast milk direct lyophilization. A previous study reported that HM-concentrate contains the adequate amount of main macro- and micronutrients for use as a nutritional resource for preterm infants with very low birth weight admitted to neonatal intensive care units. However, further details need to be elucidated about HM-concentrate composition, particularly its content of essential and potentially toxic trace elements. Therefore, this study aimed to determine the concentration of essential and toxic elements in human milk considered baseline (HM-baseline) and HM-concentrate, as well as to quantify changes in concentration of these elements after the HM concentration process. The concentration of Aluminum, Arsenic, Cadmium, Chromium, Iron, Mercury, Manganese, Nickel, Lead, Selenium, Tin, and Thallium was analyzed by inductively coupled plasma-mass spectrometry (ICP-MS). Moreover, Bayesian linear mixed effect models were applied to estimate the mean difference between HM-baseline and HM-concentrate samples. After comparison (HM-concentrate versus HM-baseline), a significant increase in concentration was observed only for Manganese (0.80 μg/L; 95% CrI [0.16; 1.43]) and Selenium (6.74 μg/L; 95% CrI [4.66; 8.86]), while Lead concentration (−6.13 μg/L; 95% CrI [-8.63; −3.61]) decreased. This study provides latest and reliable information about HM composition. After milk concentration by lyophilization, there was a significant increase only in the essential elements Manganese and Selenium. The essential micronutrient content in HM-concentrate was similar or higher than that in preterm mothers' milk, which suggests it is viable for nutritional support of preterm infants. In addition, the low concentrations of potentially toxic elements in HM-concentrate indicates that it is safe for consumption by premature newborns.

In this study, air concentrations of BaP in two different seasons (winter 2015 and summer 2016) and BaP levels in ground vegetation from Tarragona County were used as control simulations performed with the WRF-CHIMERE air quality modelling system, in order to reproduce the incidence of that hazardous chemical in air and soils. The CTM was validated for the present climatology, showing a good ability to represent air and soil concentrations of BaP over the target domain (petrochemical, chemical, urban and background sites), particularly in the wither. Then, the variation of the BaP concentrations in air and soils were simulated for the time series 1996-2015 and for the climate change scenario RCP8.5 (2031-2050). While an increase is projected for the levels in air, particularly in chemical and remote silos where the variation can go up to 10%, in terms of soil deposition the findings are the opposite, with an evident decrease in soil BaP concentrations, particularly for background sites. Finally, a potential health effect of BaP for the local population (lung cancer) was assessed. Although according to the projections the EU threshold for BaP atmospheric incidence (1 ng m(-3)) will not be reached by 2050, there will be an increase in the life-time risk of lung cancer, particularly in the most populated areas within the simulation domain. (C) 2018 Elsevier B.V. All rights reserved.

Rituximab hypersensitivity reactions are rare but are one of the main causes of rituximab elimination from antilymphoma immunochemotherapy treatments. While the clinical picture may be indistinguishable from other infusion-related reactions, hypersensitivity reactions (HSR) do not disappear and instead become more intense with subsequent administrations. Objective. To describe the use of the 12-step protocol for desensitization to intravenous rituximab in clinical practice and the complementary study of a possible IgE-mediated HSR in the context of B-cell lymphoma treatment. Methods. A 12-step rituximab desensitization protocol was performed prospectively within clinical practice in 10 patients with a history of severe infusion reactions or in patients who had a repeated reaction at subsequent doses despite taking more intense preventive measures. Skin prick tests were performed at the time of reaction and at a later time to eliminate false negatives due to possible drug interference. Results. Overall, with the desensitization protocol, 70% of patients were able to complete the scheduled immunochemotherapy. Two patients had to discontinue the therapy due to clinical persistence and the third due to lymphoma progression. Intradermal tests with 0.1% rituximab were positive in only 20% of cases, demonstrating a mechanism of hypersensitivity. Conclusions. The 12-step desensitization protocol is very effective and assumable within healthcare practice. There is a need to determine the mechanism underlying the infusion reaction in a large proportion of cases due to the risk of future drug exposure.

Vascular endothelial growth factor C (VEGFC) stimulates leukemia cell proliferation and survival, and promotes angiogenesis. We studied VEGFC expression in bone marrow samples from 353 adult acute myeloid leukemia (AML) patients and its relationship with several clinical, cytogenetic, and molecular variables. We also studied the expression of 84 genes involved in VEGF signaling in 24 patients. We found that VEGFC expression was higher in AML patients with myelodysplasia-related changes (AML-MRC) than in patients with non-AML-MRC. We also found an association between VEGFC expression and the patient cytogenetic risk group, with those with a worse prognosis having higher VEGFC expression levels. No correlation was observed between VEGFC expression and survival or complete remission. VEGFC expression strongly correlated with expression of the VEGF receptors FLT1, KDR, and NRP1. Thus, in this series, VEGFC expression was increased in AML-MRC and in subgroups with a poorer prognosis, but has no impact on survival.

Located in the southeast of Brazil, the Pardo River Basin has a large population and an economy focused on agriculture, with a strong predominance of the sugarcane agro-industry. The purpose of the study was to assess the water quality of the Pardo River Basin under a multivariate approach using limnological parameters, metal concentrations, and indicator bacteria. Nine sampling campaigns were performed during both the dry and rainy seasons. Element concentrations were determined by inductively coupled plasma spectrometry (ICP-MS, Perkin Elmer Elan 6000). A battery of test to determine limnological parameters was performed (in situ). Total coliforms and Escherichia coli were detected and quantified using Defined Substrate Technology Colilert® and multiple tube dilutions. Principal component analysis and hierarchical cluster analysis were used as multivariate exploratory analysis. In general, the results suggest the influence of rain, possible sewage discharges into the watercourse, and the input of organic matter in some sampling points in both seasons, besides the absence of riparian vegetation in much of the Pardo River. The likely influence of industrial activities that do not have great prominence in the region was supported by temporal/spatial assessment of Cr and V. The water quality monitoring of Pardo River is an important tool for environmental management, and its continuity is indicated to obtain a consistent series of systematic data and thereby support concretely the actions of planning and controlling the use of water from the Pardo River and soil around them.