MAP17 (PDZK1IP1) and pH2AX are potential predictive biomarkers for rectal cancer treatment efficacy

Rectal cancer represents approximately 10% of cancers worldwide. Preoperative chemoradiotherapy increases complete pathologic response and local control, although it offers a poor advantage in survivorship and sphincter saving compared with that of radiotherapy alone. After preoperative chemoradiotherapy, approximately 20% of patients with rectal cancer achieve a pathologic complete response to the removed surgical specimen; this response may be related to a better prognosis and an improvement in disease-free survival. However, better biomarkers to predict response and new targets are needed to stratify patients and obtain better response rates. MAP17 (PDZK1IP1) is a small, 17 kDa non-glycosylated membrane protein located in the plasma membrane and Golgi apparatus and is overexpressed in a wide variety of human carcinomas. MAP17 has been proposed as a predictive biomarker for reactive oxygen species, ROS, inducing treatments in cervical tumors or laryngeal carcinoma. Due to the increase in ROS, MAP17 is also associated with the marker of DNA damage, phosphoH2AX (pH2AX). In the present manuscript, we examined the values of MAP17 and pH2AX as surrogate biomarkers of the response in rectal tumors. MAP17 expression after preoperative chemoradiotherapy is able to predict the response to chemoradiotherapy, similar to the increase in pH2AX. Furthermore, we explored whether we can identify molecular targeted therapies that could help improve the response of these tumors to radiotherapy. In this sense, we found that the inhibition of DNA damage with olaparib increased the response to radio- and chemotherapy, specifically in tumors with high levels of pH2AX and MAP17.Spanish Ministry of Economy and Competitivity, Plan Estatal de I+D+I 2013–2016, ISCIII (Fis: PI15/00045) and CIBER de Cáncer (CB16/12/00275)co-funded by FEDER from Regional Development European Funds (European Union), Consejería de Ciencia e Innovación (CTS-1848)Consejería de Salud of the Junta de Andalucía (PI-0096–2014)

Comparison of physical-based models to measure forest resilience to fire as a function of burn severity

Producción CientíficaWe aimed to compare the potential of physical-based models (radiative transfer and pixel unmixing models) for evaluating the short-term resilience to fire of several shrubland communities as a function of their regenerative strategy and burn severity. The study site was located within the perimeter of a wildfire that occurred in summer 2017 in the northwestern Iberian Peninsula. A pre- and post-fire time series of Sentinel-2 satellite imagery was acquired to estimate fractional vegetation cover (FVC) from the (i) PROSAIL-D radiative transfer model inversion using the random forest algorithm, and (ii) multiple endmember spectral mixture analysis (MESMA). The FVC retrieval was validated throughout the time series by means of field data stratified by plant community type (i.e., regenerative strategy). The inversion of PROSAIL-D featured the highest overall fit for the entire time series (R2 > 0.75), followed by MESMA (R2 > 0.64). We estimated the resilience of shrubland communities in terms of FVC recovery using an impact-normalized resilience index and a linear model. High burn severity negatively influenced the short-term resilience of shrublands dominated by facultative seeder species. In contrast, shrublands dominated by resprouters reached pre-fire FVC values regardless of burn severity.Ministerio de Economía y Competitividad y Fondo Europeo de Desarrollo Regional (FEDER) - (project AGL2017-86075-C2-1-R)Junta de Castilla y León - (project LE005P20)British Ecological Society - (project SR22-100154

Evaluation of Prescribed Fires from Unmanned Aerial Vehicles (UAVs) Imagery and Machine Learning Algorithms

Producción CientíficaPrescribed fires have been applied in many countries as a useful management tool to prevent large forest fires. Knowledge on burn severity is of great interest for predicting post-fire evolution in such burned areas and, therefore, for evaluating the efficacy of this type of action. In this research work, the severity of two prescribed fires that occurred in “La Sierra de Uría” (Asturias, Spain) in October 2017, was evaluated. An Unmanned Aerial Vehicle (UAV) with a Parrot SEQUOIA multispectral camera on board was used to obtain post-fire surface reflectance images on the green (550 nm), red (660 nm), red edge (735 nm), and near-infrared (790 nm) bands at high spatial resolution (GSD 20 cm). Additionally, 153 field plots were established to estimate soil and vegetation burn severity. Severity patterns were explored using Probabilistic Neural Networks algorithms (PNN) based on field data and UAV image-derived products. PNN classified 84.3% of vegetation and 77.8% of soil burn severity levels (overall accuracy) correctly. Future research needs to be carried out to validate the efficacy of this type of action in other ecosystems under different climatic conditions and fire regimes.Ministerio de Economía, Industria y Competitividad - Fondo Europeo de Desarrollo Regional (project AGL2017-86075-C2-1-R)Junta de Castilla y León (project LE001P17

Influencia del sistema de control zonificado en la combinación de un suelo radiante refrescante con un fancoil de conductos

La aerotermia está siendo promovida como solución en el sector residencial tanto para la producción de agua caliente sanitaria como para la climatización con instalaciones con agua, reemplazando a la energía solar térmica y los equipos de expansión directa. Este estudio presenta el análisis, desde el punto de vista del confort térmico y el consumo de energía, de un sistema de control zonificado aplicado a una instalación de suelo radiante y fancoil de conductos, comparado con un sistema de suelo radiante y fancoils individuales. El sistema de control incluye el uso eficiente combinado de ambas unidades terminales. La capacidad de refrigeración del suelo refrescante está limitada y en climas cálidos es necesario el uso del fancoil para asegurar el confort térmico y combatir la carga latente de la zona. El sistema se ha modelado en Trnsys17 y el caso de estudio se ha aplicado a una vivienda residencial y en diferentes zonas climáticas

Reducing residual thrombotic risk in patients with peripheral artery disease : impact of the COMPASS trial

Altres ajuts: Writing and editorial assistance was funded by Bayer Hispania.Patients with peripheral artery disease (PAD) are at a high risk not only for the classical cardiovascular (CV) outcomes (major adverse cardiovascular events; MACE) but also for vascular limb events (major adverse limb events; MALE). Therefore, a comprehensive approach for these patients should include both goals. However, the traditional antithrombotic approach with only antiplatelet agents (single or dual antiplatelet therapy) does not sufficiently reduce the risk of recurrent thrombotic events. Importantly, the underlying cause of atherosclerosis in patients with PAD implies both platelet activation and the initiation and promotion of coagulation cascade, in which Factor Xa plays a key role. Therefore, to reduce residual vascular risk, it is necessary to address both targets. In the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial that included patients with stable atherosclerotic vascular disease, the rivaroxaban plus aspirin strategy (versus aspirin) markedly reduced the risk of both CV and limb outcomes, and related complications, with a good safety profile. In fact, the net clinical benefit outcome composed of MACE; MALE, including major amputation, and fatal or critical organ bleeding was significantly reduced by 28% with the COMPASS strategy, (hazard ratio: 0.72; 95% confidence interval: 0.59-0.87). Therefore, the rivaroxaban plus aspirin approach provides comprehensive protection and should be considered for most patients with PAD at high risk of such events

Antibióticos empíricos para la neumonía adquirida en la comunidad en pacientes adultos: Una revisión sistemática y un metaanálisis en red

Objetivo: El objetivo principal de este metaanálisis en red es identificar el antibiótico empírico (Em-ATB) con mayor probabilidad de ser el mejor (HPBB) en términos de (1) tasa de curación y (2) tasa de mortalidad en pacientes hospitalizados con neumonía adquirida en la comunidad (NAC) . Método: Criterios de inclusión: (1) pacientes adultos (>16 años) diagnosticados de NAC que requirieron hospitalización; (2) aleatorizados a al menos dos Em-ATB diferentes, (3) que informen de la tasa de curación y (4) que estén escritos en inglés o español. Criterios de exclusión: (1) protocolo de antibióticos ambiguo y (2) publicados exclusivamente en formato resumen o carta. Fuentes de datos: Medline, Embase, Cochrane y revisiones de citas desde el 1 de enero de 2000 hasta el 31 de diciembre de 2018. Riesgo de sesgo: Herramienta de Cochrane. Calidad de la revisión sistemática (RS): A MeaSurement Tool to Assess systematic Reviews-2. Certeza de la evidencia: Grading of Recommendations Assessment, Development and Evaluation. Análisis estadísticos: método frecuentista realizado con la biblioteca 'netmeta', paquete R. Resultados: se incluyeron 27 ensayos controlados aleatorizados (ECA) de las 41.307 citas seleccionadas inicialmente. En cuanto al riesgo de sesgo, más de una cuarta parte de los estudios presentaron riesgo bajo y ningún estudio presentó riesgo alto en todos los dominios. La calidad de la RS es moderada. Para la curación, se construyeron dos redes. Así, dos Em-ATB tienen la HPBB: cetarolina 600 mg (dos veces al día) y piperacilina 2000 mg (dos veces al día). Para la mortalidad, se construyeron tres redes. Así, tres Em-ATB tienen la HPBB: ceftriaxona 2000 mg (una vez al día) más levofloxacino 500 (dos veces al día), ertapenem 1000 mg (dos veces al día) y amikacina 250 mg (dos veces al día) más claritromicina 500 mg (dos veces al día). La certeza de la evidencia para cada resultado es moderada. Conclusiones: Para la tasa de curación, ceftarolina y piperacilina son las opciones con la HPBB. Sin embargo, para la tasa de mortalidad, las opciones son ceftriaxona más levofloxacino, ertapenem y amikacina más claritromicina. Parece necesario realizar un ECA que compare los tratamientos con el HPBB para cada evento (curación o mortalidad) (CRD42017060692).Objective: The main aim of this network meta-analysis is to identify the empiric antibiotic (Em-ATB) with the highest probability of being the best (HPBB) in terms of (1) cure rate and (2) mortality rate in hospitalised patients with community acquired pneumonia (CAP) . Method: Inclusion criteria: (1) adult patients (>16 years old) diagnosed with CAP that required hospitalisation; (2) randomised to at least two different Em-ATBs, (3) that report cure rate and (4) are written in English or Spanish. Exclusion criteria: (1) ambiguous antibiotics protocol and (2) published exclusively in abstract or letter format. Data sources: Medline, Embase, Cochrane and citation reviews from 1 January 2000 to 31 December 2018. Risk of bias: Cochrane's tool. Quality of the systematic review (SR): A MeaSurement Tool to Assess systematic Reviews-2. Certainity of the evidence: Grading of Recommendations Assessment, Development and Evaluation. Statistical analyses: frequentist method performed with the 'netmeta' library, R package. Results: 27 randomised controlled trials (RCTs) from the initial 41 307 screened citations were included. Regarding the risk of bias, more than one quarter of the studies presented low risk and no study presented high risk in all domains. The SR quality is moderate. For cure, two networks were constructed. Thus, two Em-ATBs have the HPBB: cetaroline 600 mg (two times a day) and piperacillin 2000 mg (two times a day). For mortality, three networks were constructed. Thus, three Em-ATBs have the HPBB: ceftriaxone 2000 mg (once a day) plus levofloxacin 500 (two times a day), ertapenem 1000 mg (two times a day) and amikacin 250 mg (two times a day) plus clarithromycin 500 mg (two times a day). The certainity of evidence for each results is moderate. Conclusion: For cure rate, ceftaroline and piperaciline are the options with the HPBB. However, for mortality rate, the options are ceftriaxone plus levofloxacin, ertapenem and amikacin plus clarithromycin. It seems necessary to conduct an RCT that compares treatments with the HPBB for each event (cure or mortality) (CRD42017060692)

Declared experiences of risky sexual behaviors in relation to alcohol consumption in the first year of college

Fundamentos: En universitarios, el consumo de alcohol de mayor riesgo (borracheras y binge drinking (BD), tiene consecuencias negativas sobre su desarrollo y probablemente facilita conductas sexuales de riesgo. El objetivo de este trabajo fue estudiar si las conductas sexuales de riesgo al consumir alcohol (CSRA) se asocian a los consumos de mayor riesgo. Métodos: Estudio multicéntrico transversal con datos del Proyecto uniHcos, de universitarios de 1er año de 11 universidades españolas, entre los cursos 2011-2012 y 2017- 2018. Datos recogidos mediante cuestionario autoadministrado. Se realizó un análisis uni y bivariable, evaluando la significación estadística de las diferencias de prevalencia con chi-cuadrado. Se utilizó media y desviación típica para variables cuantitativas y como estadístico de contraste t de Student. Resultados: 9.862 participantes (72,2% mujeres). El 90,3% consumió alcohol y el 60,9% tuvo borracheras en último año; el 49% tuvo BD en el último mes. El consumo en el último mes y las borracheras fueron mayores en hombres y < 21 años. Las CSRA fueron superiores entre los que se emborracharon (15,7% sexo sin protección, 1,9% abuso sexual y 0,7% aprovecharse sexualmente) y consumieron en BD (17,1%, 1,9% y 0,7%). Las mujeres con ambos consumos de riesgo presentaron más abusos sexuales (2,2%), y los hombres fueron quienes más se aprovecharon sexualmente de otros (borracheras:1,2%; BD: 1,3%). Conclusiones: El consumo de alcohol está por encima de grupos similares. El BD tiene un patrón similar por género y edad. Las CSRA se asocian a los consumos de mayor riesgo, no detectándose en este grupo diferencias por género en sexo sin protección, sí en otras CSRA.Objective: In college students, higher risk alcohol consumption (drunkenness and binge drinking-BD) has negative consequences on their development and and probably facilitates risk sexual behaviors. The objective was to study if risky sexual behaviors when consuming alcohol (RSBA) are associated with higher risk consumption. Methods: Cross-sectional multicenter study with UniHcos Project, 1st year university students from 11 universities in Spain, academic years 2011-2012 to 2017-2018 data. This data were collected by self-administered questionnaire. A uni and bivariate analysis was performed, evaluated the statistical significance of the differences in prevalence with chi-square. Mean and standard deviation were used for quantitative variables and Student's t test statistic was used. Results: 9,862 subjects (72.2% women). 90.3% reported having consumed alcohol and 60.9% had drunk the last year, 49% BD in last month. It was deteded in men, significantly higher consumption in the last month and drunkenness. Last month consumption and drunkenness were significantly higher in men and in <21 years. The RSBA were significantly higher among who were drunk (15.7% unprotected sex, 1.9% sexual abuse and 0.7% taking sexual advantage) and had BD (17.1%, 1.9% and 0.7 %). Women with both risk consumptions had more sexual abuse (2.2%), and men had greater behaviors of taking sexual advantage of someone (drunk: 1.2%; BD: 1.3%). Conclusions: Alcohol consumption was above similar groups. BD consumption was similar by gender and age. Risk sexual behaviors appear mainly in problematic consumption. Gender differences are not detected in alcohol consumers in unprotected sex but deteded in the rest.Financiación: El estudio ha sido financiado por el Plan Nacional Sobre Drogas del Ministerio de Salud, Servicios Sociales e Igualdad. Convocatoria de 2010 y de 2013. (Códigos: 2010/145 and 2013/034) y por el Instituto de Salud Carlos III a través de la convocatoria del FIS (Fondo de Investigación Sanitaria) de 2016 (PI16/01947)

A case-control of patients with COVID-19 to explore the association of previous hospitalisation use of medication on the mortality of COVID-19 disease: a propensity score matching analysis

Data from several cohorts of coronavirus disease 2019 (COVID-19) suggest that the most common comorbidities for severe COVID-19 disease are the elderly, high blood pressure, and diabetes; however, it is not currently known whether the previous use of certain drugs help or hinder recovery. This study aims to explore the association of previous hospitalisation use of medication on the mortality of COVID-19 disease. A retrospective case-control from two hospitals in Madrid, Spain, included all patients aged 18 years or above hospitalised with a diagnosis of COVID-19. A Propensity Score matching (PSM) analysis was performed. Confounding variables were considered to be age, sex, and the number of comorbidities. Finally, 3712 patients were included. Of these, 687 (18.5%) patients died (cases). The 22,446 medicine trademarks used previous to admission were classified according to the ATC, obtaining 689 final drugs; all of them were included in PSM analysis. Eleven drugs displayed a reduction in mortality: azithromycin, bemiparine, budesonide-formoterol fumarate, cefuroxime, colchicine, enoxaparin, ipratropium bromide, loratadine, mepyramine theophylline acetate, oral rehydration salts, and salbutamol sulphate. Eight final drugs displayed an increase in mortality: acetylsalicylic acid, digoxin, folic acid, mirtazapine, linagliptin, enalapril, atorvastatin, and allopurinol. Medication associated with survival (anticoagulants, antihistamines, azithromycin, bronchodilators, cefuroxime, colchicine, and inhaled corticosteroids) may be candidates for future clinical trials. Drugs associated with mortality show an interaction with the underlying condition

High prognostic value of measurable residual disease detection by flow cytometry in chronic lymphocytic leukemia patients treated with front-line fludarabine, cyclophosphamide, and rituximab, followed by three years of rituximab maintenance

It has been postulated that monitoring measurable residual disease (MRD) could be used as a surrogate marker of progression-free survival (PFS) in chronic lymphocytic leukemia (CLL) patients after treatment with immunochemotherapy regimens. In this study, we analyzed the outcome of 84 patients at 3 years of follow-up after first-line treatment with fludarabine, cyclophosphamide and rituximab (FCR) induction followed by 36 months of rituximab maintenance thearpy. MRD was assessed by a quantitative four-color flow cytometry panel with a sensitivity level of 10-4. Eighty out of 84 evaluable patients (95.2%) achieved at least a partial response or better at the end of induction. After clinical evaluation, 74 patients went into rituximab maintenance and the primary endpoint was assessed in the final analysis at 3 years of follow-up. Bone marrow (BM) MRD analysis was performed after the last planned induction course and every 6 months in cases with detectable residual disease during the 36 months of maintenance therapy. Thirty-seven patients (44%) did not have detectable residual disease in the BM prior to maintenance therapy. Interestingly, 29 patients with detectable residual disease in the BM after induction no longer had detectable disease in the BM following maintenance therapy. After a median followup of 6.30 years, the median overall survival (OS) and PFS had not been reached in patients with either undetectable or detectable residual disease in the BM, who had achieved a complete response at the time of starting maintenance therapy. Interestingly, univariate analysis showed that after rituximab maintenance OS was not affected by IGHV status (mutated vs. unmutated OS: 85.7% alive at 7.2 years vs. 79.6% alive at 7.3 years, respectively). As per protocol, 15 patients (17.8%), who achieved a complete response and undetectable peripheral blood and BM residual disease after four courses of induction, were allowed to stop fludarabine and cyclophosphamide and complete two additional courses of rituximab and continue with maintenance therapy for 18 cycles. Surprisingly, the outcome in this population was similar to that observed in patients who received the full six cycles of the induction regimen. These data show that, compared to historic controls, patients treated with FCR followed by rituximab maintenance have high-quality responses with fewer relapses and improved OS. The tolerability of this regime is favorable. Furthermore, attaining an early undetectable residual disease status could shorten the duration of chemoimmunotherapy, reducing toxicities and preventing long-term side effects. The analysis of BM MRD after fludarabine-based induction could be a powerful predictor of post-maintenance outcomes in patients with CLL undergoing rituximab maintenance and could be a valuable tool to identify patients at high risk of relapse, influencing further treatment strategies

Acenocoumarol Pharmacogenetic Dosing Algorithm versus Usual Care in Patients with Venous Thromboembolism: A Randomised Clinical Trial

Patients with venous thromboembolism (VTE) require immediate treatment with anticoagulants such as acenocoumarol. This multicentre randomised clinical trial evaluated the effectiveness of a dosing pharmacogenetic algorithm versus a standard-of-care dose adjustment at the beginning of acenocoumarol treatment. We included 144 patients with VTE. On the day of recruitment, a blood sample was obtained for genotyping (CYP2C9*2, CYP2C9*3, VKORC1, CYP4F2, APOE). Dose adjustment was performed on day 3 or 4 after the start of treatment according to the assigned group and the follow-up was at 12 weeks. The principal variable was the percentage of patients with an international normalised ratio (INR) within the therapeutic range on day 7. Thirty-four (47.2%) patients had an INR within the therapeutic range at day 7 after the start of treatment in the genotype-guided group compared with 14 (21.9%) in the control group (p = 0.0023). There were no significant differences in the time to achieve a stable INR, the number of INRs within the range in the first 6 weeks and at the end of study. Our results suggest the use of a pharmacogenetic algorithm for patients with VTE could be useful in achieving target INR control in the first days of treatment