The authors performed a systematic review and meta-analysis of randomized and nonrandomized trials on the efficacy of dexrazoxane in patients with breast cancer who were treated with anthracyclines ...with or without trastuzumab.
Breast cancer treatment with anthracyclines and trastuzumab is associated with an increased risk of cardiotoxicity. Among the various strategies to reduce the risk of cardiotoxicity, dexrazoxane is an option for primary prevention, but it is seldom used in clinical practice.
Online databases were searched from January 1990 up to March 1, 2019, for clinical trials on the use of dexrazoxane for the prevention of cardiotoxicity in patients with breast cancer receiving anthracyclines with or without trastuzumab. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model meta-analysis.
Seven randomized trials and 2 retrospective trials with a total of 2,177 patients were included. Dexrazoxane reduced the risk of clinical heart failure (RR: 0.19; 95% CI: 0.09 to 0.40; p < 0.001) and cardiac events (RR: 0.36; 95% CI: 0.27 to 0.49; p < 0.001) irrespective of previous exposure to anthracyclines. The rate of a partial or complete oncological response, overall survival, and progression-free survival were not affected by dexrazoxane.
Dexrazoxane reduced the risk of clinical heart failure and cardiac events in patients with breast cancer undergoing anthracycline chemotherapy with or without trastuzumab and did not significantly impact cancer outcomes. However, the quality of available evidence is low, and further randomized trials are warranted before the systematic implementation of this therapy in clinical practice.
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Background:
Cardiovascular comorbidities such as hypertension and inflammatory response dysregulation are associated with worse COVID-19 prognoses. Different cytokines have been proposed to play ...vital pathophysiological roles in COVID-19 progression, but appropriate prognostic biomarkers remain lacking. We hypothesized that the combination of immunological and clinical variables at admission could predict the clinical progression of COVID-19 in hypertensive patients.
Methods:
The levels of biomarkers, including C-reactive protein, lymphocytes, monocytes, and a panel of 29 cytokines, were measured in blood samples from 167 hypertensive patients included in the BRACE-CORONA trial. The primary outcome was the highest score during hospitalization on the modified WHO Ordinal Scale for Clinical Improvement. The probability of progression to severe disease was estimated using a logistic regression model that included clinical variables and biomarkers associated significantly with the primary outcome.
Results:
During hospitalization, 13 (7.8%) patients showed progression to more severe forms of COVID-19, including three deaths. Obesity, diabetes, oxygen saturation, lung involvement on computed tomography examination, the C-reactive protein level, levels of 15 cytokines, and lymphopenia on admission were associated with progression to severe COVID-19. Elevated levels of interleukin-10 and interleukin-12 (p70) combined with two or three of the abovementioned clinical comorbidities were associated strongly with progression to severe COVID-19. The risk of progression to severe disease reached 97.5% in the presence of the five variables included in our model.
Conclusions:
This study demonstrated that interleukin-10 and interleukin-12 (p70) levels, in combination with clinical variables, at hospital admission are key biomarkers associated with an increased risk of disease progression in hypertensive patients with COVID-19.
This position statement from the Heart Failure Association of the European Society of Cardiology Cardio‐Oncology Study Group in collaboration with the International Cardio‐Oncology Society presents ...practical, easy‐to‐use and evidence‐based risk stratification tools for oncologists, haemato‐oncologists and cardiologists to use in their clinical practice to risk stratify oncology patients prior to receiving cancer therapies known to cause heart failure or other serious cardiovascular toxicities. Baseline risk stratification proformas are presented for oncology patients prior to receiving the following cancer therapies: anthracycline chemotherapy, HER2‐targeted therapies such as trastuzumab, vascular endothelial growth factor inhibitors, second and third generation multi‐targeted kinase inhibitors for chronic myeloid leukaemia targeting BCR‐ABL, multiple myeloma therapies (proteasome inhibitors and immunomodulatory drugs), RAF and MEK inhibitors or androgen deprivation therapies. Applying these risk stratification proformas will allow clinicians to stratify cancer patients into low, medium, high and very high risk of cardiovascular complications prior to starting treatment, with the aim of improving personalised approaches to minimise the risk of cardiovascular toxicity from cancer therapies.
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COVID-19 is associated with a prothrombotic state leading to adverse clinical outcomes. Whether therapeutic anticoagulation improves outcomes in patients hospitalised with COVID-19 is unknown. We ...aimed to compare the efficacy and safety of therapeutic versus prophylactic anticoagulation in this population.
We did a pragmatic, open-label (with blinded adjudication), multicentre, randomised, controlled trial, at 31 sites in Brazil. Patients (aged ≥18 years) hospitalised with COVID-19 and elevated D-dimer concentration, and who had COVID-19 symptoms for up to 14 days before randomisation, were randomly assigned (1:1) to receive either therapeutic or prophylactic anticoagulation. Therapeutic anticoagulation was in-hospital oral rivaroxaban (20 mg or 15 mg daily) for stable patients, or initial subcutaneous enoxaparin (1 mg/kg twice per day) or intravenous unfractionated heparin (to achieve a 0·3–0·7 IU/mL anti-Xa concentration) for clinically unstable patients, followed by rivaroxaban to day 30. Prophylactic anticoagulation was standard in-hospital enoxaparin or unfractionated heparin. The primary efficacy outcome was a hierarchical analysis of time to death, duration of hospitalisation, or duration of supplemental oxygen to day 30, analysed with the win ratio method (a ratio >1 reflects a better outcome in the therapeutic anticoagulation group) in the intention-to-treat population. The primary safety outcome was major or clinically relevant non-major bleeding through 30 days. This study is registered with ClinicalTrials.gov (NCT04394377) and is completed.
From June 24, 2020, to Feb 26, 2021, 3331 patients were screened and 615 were randomly allocated (311 50% to the therapeutic anticoagulation group and 304 50% to the prophylactic anticoagulation group). 576 (94%) were clinically stable and 39 (6%) clinically unstable. One patient, in the therapeutic group, was lost to follow-up because of withdrawal of consent and was not included in the primary analysis. The primary efficacy outcome was not different between patients assigned therapeutic or prophylactic anticoagulation, with 28 899 (34·8%) wins in the therapeutic group and 34 288 (41·3%) in the prophylactic group (win ratio 0·86 95% CI 0·59–1·22, p=0·40). Consistent results were seen in clinically stable and clinically unstable patients. The primary safety outcome of major or clinically relevant non-major bleeding occurred in 26 (8%) patients assigned therapeutic anticoagulation and seven (2%) assigned prophylactic anticoagulation (relative risk 3·64 95% CI 1·61–8·27, p=0·0010). Allergic reaction to the study medication occurred in two (1%) patients in the therapeutic anticoagulation group and three (1%) in the prophylactic anticoagulation group.
In patients hospitalised with COVID-19 and elevated D-dimer concentration, in-hospital therapeutic anticoagulation with rivaroxaban or enoxaparin followed by rivaroxaban to day 30 did not improve clinical outcomes and increased bleeding compared with prophylactic anticoagulation. Therefore, use of therapeutic-dose rivaroxaban, and other direct oral anticoagulants, should be avoided in these patients in the absence of an evidence-based indication for oral anticoagulation.
Coalition COVID-19 Brazil, Bayer SA.
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The Brazilian Cerrado is one of the most biodiverse savannas in the world, yet 46% of its original cover has been cleared to make way for crops and pastures. These extensive land‐use transitions ...(LUTs) are expected to influence regional climate by reducing evapotranspiration (ET), increasing land surface temperature (LST), and ultimately reducing precipitation. Here, we quantify the impacts of LUTs on ET and LST in the Cerrado by combining MODIS satellite data with annual land use and land cover maps from 2006 to 2019. We performed regression analyses to quantify the effects of six common LUTs on ET and LST across the entire gradient of Cerrado landscapes. Results indicate that clearing forests for cropland or pasture increased average LST by ~3.5°C and reduced mean annual ET by 44% and 39%, respectively. Transitions from woody savannas to cropland or pasture increased average LST by 1.9°C and reduced mean annual ET by 27% and 21%, respectively. Converting native grasslands to cropland or pasture increased average LST by 0.9 and 0.6°C, respectively. Conversely, grassland‐to‐pasture transitions increased mean annual ET by 15%. To date, land changes have caused a 10% reduction in water recycled to the atmosphere annually and a 0.9°C increase in average LST across the biome, compared to the historic baseline under native vegetation. Global climate changes from increased atmospheric greenhouse gas concentrations will only exacerbate these effects. Considering potential future scenarios, we found that abandoning deforestation control policies or allowing legal deforestation to continue (at least 28.4 Mha) would further reduce yearly ET (by −9% and −3%, respectively) and increase average LST (by +0.7 and +0.3°C, respectively) by 2050. In contrast, policies encouraging zero deforestation and restoration of the 5.2 Mha of illegally deforested areas would partially offset the warming and drying impacts of land‐use change.
Resumo
O Cerrado brasileiro é uma das savanas mais biodiversas do mundo. Apesar disso, 46% da sua cobertura original foi desmatada para dar lugar a cultivos agrícolas e pastos. Estas extensas transições de uso do solo (LUT) têm o potencial de influenciar o clima regional, reduzindo a evapotranspiração (ET), aumentando a temperatura da superfície terrestre (LST) e por fim reduzindo a precipitação. O objetivo deste estudo foi quantificar os impactos de LUTs sobre ET e LST no Cerrado, combinando dados do satélite MODIS com mapas anuais de uso e cobertura do solo de 2006–2019. Foram realizadas análises de regressão para quantificar os efeitos de seis LUTs usuais sobre ET e LST, ao longo de todo o gradiente de paisagens do Cerrado. Os resultados indicaram que a retirada de florestas para dar lugar à agricultura ou pastagem aumentou a LST média em ~3.5°C e reduziu a ET média anual em 44% e 39%, respectivamente. Transições de formações savânicas para agricultura ou pastagem aumentaram a LST média em 1.9°C e reduziram a ET média anual em 27% e 21%, respectivamente. A conversão de campos nativos para agricultura ou pastagem aumentou a LST média em 0.9 e 0.6°C, respectivamente. Em contrapartida, transições de formações campestres nativas para pastagens aumentaram a ET média anual em 15%. Até o momento, as mudanças de uso do solo causaram redução de 10% da água reciclada para a atmosfera anualmente e aumento de 0.9°C da LST média ao longo do bioma, em comparação com a linha de base histórica sob vegetação nativa. As mudanças climáticas globais decorrentes do aumento das concentrações atmosféricas de gases do efeito estufa irão exacerbar esses efeitos. Considerando potenciais cenários futuros, observou‐se que o abandono das políticas de controle do desmatamento ou o avanço do desmatamento legal (ao menos 28.4 Mha) reduziriam a ET anual (em −9% e −3%, respectivamente) e aumentariam a LST média (em +0.7 e +0.3ºC, respectivamente) até 2050. Por outro lado, políticas que promovam desmatamento zero e restauração dos 5.2 Mha de áreas ilegalmente desmatadas compensariam parte dos impactos de aquecimento e seca causados por alterações de uso do solo.
Researchers have long studied the role of tropical forests in regulating climate. This study shows that grasslands and savannas are also critical for regulating heat and moisture exchange. We address the historic and projected impacts of agricultural expansion on regional climate in the Brazilian Cerrado, one of the most biodiverse savannas in the world. Large‐scale conversion of forests and savannas to agricultural land uses has caused significant warming and drying in a region already facing water scarcity. Grassland conversion has also contributed to increased surface temperatures. Recent weakening of environmental policies could further threaten the region's climatic stability.
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•A solvent-free and multifunctional coating using PDMS and propolis was developed.•EIS experiments showed that propolis improve the anticorrosive property of the paint.•Excellent ...antifouling efficiency of the paint containing propolis over 11 months.•Films formulated with propolis decrease the adhesion of the Staphylococcus aureus.
The development of new green alternatives for anticorrosive and antifouling coatings is essential for the conservation of the environment. A coating with more than one functionality, for example both anticorrosion and antifouling is of great interest for cost reduction and for improved coating efficiency. In this work, the multifunctional effect of propolis within a silicone matrix coating was evaluated. Fourier transform infrared (FTIR) and 13C nuclear magnetic resonance (13C NMR) analyses confirmed the presence of several compounds with active properties (e.g. polyphenols, cinnamic acid, ferulic acid, and diterpenes). The addition of propolis and TiO2 increased the thermal stability of the final coating while keeping the water contact angle of the silicone, near to 98°. Electrochemical impedance spectroscopy (EIS) experiments showed that the presence of propolis increased the anticorrosive properties, and bacterial experiments showed decreased adhesion of the gram-positive bacteria Staphylococcus aureus (ATCC 6538). Marine experiments also showed the excellent antifouling efficiency of the paint containing propolis over 11 months. The use of a natural pigment allied to a solvent free resin contributes to the formulation of more environmentally friendly paints.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
This study explores the potential of geranium essential oil as a natural solution for combating marine biofouling, addressing the environmental concerns associated with commercial antifouling ...coatings. Compounds with bactericidal activities were identified by
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Carbon nuclear magnetic resonance (
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C NMR). Thermogravimetric analysis (TGA) revealed minimal impact on film thermal stability, maintaining suitability for antifouling applications. The addition of essential oil induced changes in the morphology of the film and Fourier transform infrared spectroscopy (FTIR) analysis indicated that oil remained within the film. Optical microscopy showed an increase in coating porosity after immersion in a marine environment. A total of 18 bacterial colonies were isolated, with Psychrobacter adeliensis and Shewanella algidipiscicola being the predominant biofilm-forming species. The geranium essential oil-based coating demonstrated the ability to reduce the formation of Psychrobacter adeliensis biofilms and effectively inhibit macrofouling adhesion for a duration of 11 months.
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Three distinct biological reactors fed with synthetic medium (UASB_Control), synthetic medium and linear alkylbenzene sulfonate (LAS; UASB_SL), and real laundry wastewater (UASB_LW) were compared ...using a metatranscriptomic approach to determine putative bioindicator genes and taxonomies associated to all steps of anaerobic LAS biodegradation pathway. A homemade bioinformatics pipeline combined with an R workflow was developed to perform the RNAseq data analysis. UASB_SL and UASB_LW showed similar values of LAS biological degradation (~47%) and removal (53–55%). Rarefaction analysis revealed that 1–2 million reads were sufficient to access the whole functional capacity. In the first step of LAS biodegradation pathway, fumarate reductase subunit C was detected and taxonomically assigned to the genus Syntrophobacter (0.002% - UASB_SL; 0.0015% - UASB_LW; not detected - UASB_Control). In the second step, many enzymes related to beta-oxidation were observed and most of them with low relative abundance in UASB Control and taxonomically related with Smithella, Acinetobacter and Syntrophorhabdus. For the ring cleavage step, the abundance of 6 OCH CoA hydrolase putative gene was ten times higher in UASB_SL and UASB_LW when compared to UASB_Control, and assigned to Desulfomonile and Syntrophorhabdus. Finally, the adenylylsulfate reductase, taxonomically related with Desulfovibrio and Desulfomonile, was observed in the desulfonation step with the highest relative abundance in UASB_LW.
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•Metatranscriptomic comparison among biological reactors applied to surfactant removal•Percentages of LAS removal (~50%) were similar among the reactors.•Sequencing effort was sufficient to access the functions of the microbiomes.•Active genes detected in each step of LAS removal•Microbial active core related to LAS degradation defined and explored
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Hemostatic abnormalities and thrombotic risk associated with coronavirus disease 2019 (COVID-19) are among the most discussed topics in the management of this disease. The aim of this position paper ...is to provide the opinion of Brazilian experts on the thromboprophylaxis and management of thrombotic events in patients with suspected COVID-19, in the sphere of healthcare in Brazil. To do so, the Brazilian Society of Thrombosis and Hemostasis (BSTH) and the Thrombosis and Hemostasis Committee of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy (ABHH) have constituted a panel of experts to carefully review and discuss the available evidence about this topic. The data discussed in this document was reviewed by May 9, 2020. Recommendations and suggestions reflect the opinion of the panel and should be reviewed periodically as new evidence emerges.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The use of rue extract and ginger oleoresin as natural antifouling agents in a silicone matrix was verified in this work.
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C nuclear magnetic resonance (
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C NMR) analysis identified a series of ...compounds with bactericidal properties in the two investigated natural products. Thermogravimetric analyses showed that the addition of rue extract and ginger oleoresin in the silicone matrix increased the thermal stability of the formed films. Electrochemical impedance spectroscopy analysis showed that the presence of both antifouling agents increases the velocity of water diffusion into the film, improving contact between marine water and the two products. Fourier transform infrared spectroscopy confirms that both antifouling agents were trapped inside the silicone matrix. Bacterial adhesion tests showed that rue extract reduced the adhesion of gram-negative bacteria,
Escherichia coli
, while ginger oleoresin did not show any significant effect. Optical microscopy images demonstrated that the presence of rue extract slightly increased the film’s porosity without impairing the silicone hydrophobicity, while ginger oleoresin significantly altered the film’s morphology (reducing the water contact angle). Finally, the sample containing rue extract showed excellent results against marine fouling after 6 months of immersion in a real marine environment. The polymer containing ginger oleoresin showed satisfactory results against marine fouling; however, the film showed adhesion failures after 6 months.
Graphic abstract
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ