NT-proBNP as predictor factor of cardiotoxicity during trastuzumab treatment in breast cancer patients

Background Trastuzumab is a drug used in HER2-positive breast cancer that increases patient survival. Due to cardiotoxicity is the most important side effect of trastuzumab treatment, cardiac monitoring should be a priority. The purpose of this study is to evaluate plasma NT-proBNP level and major cardiovascular risk factors as possible early predictors of trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients. Methods We conducted a retrospective observational study involving 66 patients with HER2-positive breast cancer treated with trastuzumab. Left ventricle ejection fraction (LVEF), NT-proBNP values, and the history of cardiovascular risk factors were collected. Cardiotoxicity was diagnosed considering a decrease of the LVEF from baseline or clinical manifestation of congestive heart failure. NT-proBNP cut-off points were considered to establish normal or abnormal values according to patient age. Results 27.3% of the patients suffered cardiotoxicity during trastuzumab treatment. Most cases were diagnosed due to the appearance of cardiac symptomatology (66.7%). Logistic regression analysis showed a significant association of diabetes mellitus (OR 5.9, 95% CI 1.2–28.5, p = 0.028) and high NT-proBNP levels (OR 22.0, 95% CI 5.7–85.4, p < 0.0001) with the development of trastuzumab-induced cardiotoxicity. Conclusion NT-proBNP levels above the upper limit of the normal range adjusted to age or diabetes mellitus seem to be associated with a higher risk of developing cardiotoxicity. However, some limitations of the present study make necessary further studies aimed to clarify whether NT-proBNP and diabetes-associated markers determinations can be useful in the monitoring of cardiotoxicity risk in breast cancer patients undergoing trastuzumab therapy.Ramon Areces Foundation, Madrid, Spai

Choosing a travel agency franchise by mean of a global composite indicator: an application in Spain

This paper highlights the complexity of the franchise partner selection process from a franchisee's perspective. The purpose of this article is, firstly, to propose the definition of a system of indicators which include all the relevant information which the potential franchisee should take into consideration when choosing a chain secondly, to obtain a global composite indicator for the construction of a ranking of franchisors. In order to illustrate the procedure, a sample of travel agency franchisors in Spain and a suitable database to quantify the indicators are considered. The paper concludes constructing a complete order of the franchisors in the travel agency industry. In addition, the results show the most important characteristics of franchisors that potential franchisees must take into account. The value of the paper is significant as it provides a practical frame – work for potential franchisees in the selection of franchisors. First published online: 12 Sep 201

High-throughput screening of the thermoelastic properties of ultrahigh-temperature ceramics

Ultrahigh-temperature ceramics (UHTCs) are a group of materials with high technological interest because of their applications in extreme environments. However, their characterization at high temperatures represents the main obstacle for their fast development. Obstacles are found from an experimental point of view, where only few laboratories around the world have the resources to test these materials under extreme conditions, and also from a theoretical point of view, where actual methods are expensive and difficult to apply to large sets of materials. Here, a new theoretical high-throughput framework for the prediction of the thermoelastic properties of materials is introduced. This approach can be systematically applied to any kind of crystalline material, drastically reducing the computational cost of previous methodologies up to 80% approximately. This new approach combines Taylor expansion and density functional theory calculations to predict the vibrational free energy of any arbitrary strained configuration, which represents the bottleneck in other methods. Using this framework, elastic constants for UHTCs have been calculated in a wide range of temperatures with excellent agreement with experimental values, when available. Using the elastic constants as the starting point, other mechanical properties such a bulk modulus, shear modulus, or Poisson ratio have been also explored, including upper and lower limits for polycrystalline materials. Finally, this work goes beyond the isotropic mechanical properties and represents one of the most comprehensive and exhaustive studies of some of the most important UHTCs, charting their anisotropy and thermal and thermodynamical properties.Ministerio de Ciencia e Innovación PID2019-106871GB-I00European Union 752608Red Española de Supercomputación QS-2019-2-0006, QS-2019-3-0021, QS-2020-2-003

Advanced Exergy Analysis of an Integrated SOFC-Adsorption Refrigeration Power System

In this chapter, an exergy analysis applied to a solid oxide fuel cell (SOFC)/vapor adsorption refrigeration (VAR) system is presented. The influences of four significant parameters (current density, inlet fuel temperature, fuel utilization and steam-to-carbon ratio) on the exergy efficiency of both the SOFC stack and the SOFC-VAR system are investigated. In order to do so, a mathematical model is constructed in Engineering Equation Solver (EES) software to generate the simulations. The analysis shows that the calculated exergy efficiency is around 8% lower than the energy efficiency for both cases. Moreover, it is found that most of the causes of irreversibilities in the system are due to electronic and ionic conduction in the components. It is also shown that the exergy efficiency is substantially sensitive to fuel inlet temperature, which is evidenced by a bending-over behavior. Finally, in accordance with the calculated efficiency defects, the main exergy destructions are present in the heat exchangers, the SOFC, the afterburner and the generator

Real-world data of fulvestrant as first-line treatment of postmenopausal women with estrogen receptor-positive metastatic breast cancer

Goals of endocrine therapy for advanced breast cancer (ABC) include prolonging survival rates, maintaining the quality of life, and delaying the initiation of chemotherapy. We evaluated the effectiveness of fulvestrant as first-line in patients with estrogen receptor (ER)-positive ABC with relapse during or after adjuvant anti-estrogenic therapy in real-world settings. Retrospective, observational study involving 171 postmenopausal women with ER-positive ABC who received fulvestrant as first-line between January 2011 and May 2018 in Spanish hospitals. With a median follow-up of 31.4 months, the progression-free survival (PFS) with fulvestrant was 14.6 months. No differences were seen in the visceral metastatic (14.3 months) versus non-visceral (14.6 months) metastatic subgroup for PFS. Overall response rate and clinical benefit rate were 35.2% and 82.8%. Overall survival was 43.1 months. The duration of the clinical benefit was 19.2 months. Patients with ECOG performance status 0 at the start of treatment showed a significant greater clinical benefit rate and overall survival than with ECOG 1-2. Results in real-world settings are in concordance with randomized clinical trials. Fulvestrant continues to demonstrate clinical benefits in real-world settings and appears be well tolerated as first-line for the treatment of postmenopausal women with ER-positive ABC

Use of rivaroxaban and acetylsalicylic acid as a combined treatment for peripheral arterial disease in Central Military Hospital

Background: The objective of this research was to evaluate the behavior of 3 risk indicators for peripheral arterial disease in patients under oral treatment with rivaroxaban 2.5 mg every 12 hours plus, acetylsalicylic acid 100 mg every 24 hours. It was hypothesized that the oral combination of rivaroxaban and acetylsalicylic acid presents a therapeutic advantage over other treatments.Methods: A prospective longitudinal and non-randomized study of a single center was performed. 59 patients with peripheral arterial disease were included and treated with acetylsalicylic acid + rivaroxaban. Peak systolic velocity, ankle-brachial index and C reactive protein index were evaluated.Results: Significant changes were found at month 1 and 3 of follow-up in maximum systolic velocity, ankle-arm index and C-reactive protein index. The baseline peak systolic velocity (PSV) in the anterior tibial artery had significant differences after one month of treatment (p=0.001) and after 3 months (p=0.001). The baseline PSV in the posterior tibial artery had significant differences compared to the values found at the month of treatment (p=0.001) and 3 months (p=0.001). In the ankle-brachial index a baseline median of 0.790 was found, one month after the treatment of 0.795 (p=0.147) and 3 months after 0.800 (p=0.019). The mean baseline C-reactive protein obtained was 73.142 mg/l, at one month 87.233 mg/l (p=0.001) and at 3 months at 79.009 mg/l (p=0.294) with a standard deviation of 67.18, 74.78 and 69.69 respectively.Conclusions: The combined use of acetylsalicylic acid and rivaroxaban allows a clinical improvement in patients with peripheral arterial disease

TGFβ Governs the Pleiotropic Activity of NDRG1 in Triple-Negative Breast Cancer Progression

In triple-negative breast cancer (TNBC), the pleiotropic NDRG1 (N-Myc downstream regulated gene 1) promotes progression and worse survival, yet contradictory results were documented, and the mechanisms remain unknown. Phosphorylation and localization could drive NDRG1 pleiotropy, nonetheless, their role in TNBC progression and clinical outcome was not investigated. We found enhanced p-NDRG1 (Thr346) by TGFβ1 and explored whether it drives NDRG1 pleiotropy and TNBC progression. In tissue microarrays of 81 TNBC patients, we identified that staining and localization of NDRG1 and p-NDRG1 (Thr346) are biomarkers and risk factors associated with shorter overall survival. We found that TGFβ1 leads NDRG1, downstream of GSK3β, and upstream of NF-κB, to differentially regulate migration, invasion, epithelial-mesenchymal transition, tumor initiation, and maintenance of different populations of cancer stem cells (CSCs), depending on the progression stage of tumor cells, and the combination of TGFβ and GSK3β inhibitors impaired CSCs. The present study revealed the striking importance to assess both total NDRG1 and p-NDRG1 (Thr346) positiveness and subcellular localization to evaluate patient prognosis and their stratification. NDRG1 pleiotropy is driven by TGFβ to differentially promote metastasis and/or maintenance of CSCs at different stages of tumor progression, which could be abrogated by the inhibition of TGFβ and GSK3β.Instituto de Salud Carlos III European Commission PI15/00336 PI19/01533 CP14/00197 CP19/00029 PIE16/00045Ministry of Science and Innovation, Spain (MICINN)Instituto de Salud Carlos IIISpanish Government RTI2018.101309B-C22Chair "Doctors Galera-Requena in cancer stem cell research" CMC-CTS963European Regional Development Fund (European Union)Ministerio de Universidades FPU19/04450Junta de Andalucia RH-0139-2020Sistema Nacional de Garantia Juvenil (Fondo Social Europeo) 8064Junta de Andalucia, Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades DOC_01686Fundacion Cientifica Asociacion Espanola Contra el Cancer, Junta Provincial de Jaen (AECC) PRDJA19001BLA

Alternative Eco-Friendly Methods in the Control of Post-Harvest Decay of Tropical and Subtropical Fruits

The effectiveness on several fruits by the application of alternative methods against fungi is summarized in the present chapter. Several investigations have reported the efficacy of these technologies for controlling fungal infections. Currently, high post-harvest loses have been reported due to several factors such as inefficient management, lack of training for farmers, and problems with appropriate conditions for storage of fruits and vegetables. Even now, in many countries, post-harvest disease control is led by the application of chemical fungicides. However, in this time, awareness about fungi resistance, environmental, and health issues has led to the research of eco-friendly and effective alternatives for disease management. The pathogen establishment on fruits can be affected by the application of GRAS compounds like chitosan, essential oils, salts, among others; besides, their efficacy can be enhanced by their combination with other technologies like ultrasound. Thus, the applications of these alternatives are suitable approaches for post-harvest management of fruits

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation