Objectives: Immunostimulatory therapies using immune checkpoint blockers show clinical activity in a subset of glioblastoma (GBM) patients. Several inhibitory mechanisms play a relevant role in the immune response to GBM. With the objective of analyzing the tumor immune microenvironment and its clinical significance, we quantified several relevant immune biomarkers. Design: We studied 76 primary (non-recurrent) GBMs with sufficient clinical follow-up, including a subgroup of patients treated with a dendritic cell vaccine. The IDH-mutation, EGFR-amplification, and MGMT methylation statuses were determined. Several relevant immune biomarkers, including CD163, CD8, PD1, and PDL1, were quantified in representative selected areas by digital image analysis and semiquantitative evaluation. The percentage of each immune expression was calculated with respect to the total number of tumor cells. Results: All GBMs were wild-type IDH, with a subgroup of classical GBMs according to the EGFR amplification (44%). Morphologically, CD163 immunostained microglia and intratumor clusters of macrophages were observed. A significant direct correlation was found between the expression of CD8 and the mechanisms of lymphocyte immunosuppression, in such a way that higher values of CD8 were directly associated with higher values of CD163 (p < 0.001), PDL1 (0.026), and PD1 (0.007). In a multivariate analysis, high expressions of CD8+ (HR = 2.05, 95%CI (1.02-4.13), p = 0.034) and CD163+ cells (HR 2.50, 95%CI (1.29-4.85), p = 0.007), were associated with shorter survival durations. The expression of immune biomarkers was higher in the non-classical (non-EGFR amplified tumors) GBMs. Other relevant prognostic factors were age, receipt of the dendritic cell vaccine, and MGMT methylation status. Conclusions: In accordance with the inverse correlation between CD8 and survival and the direct correlation between effector cells and CD163 macrophages and immune-checkpoint expression, we postulate that CD8 infiltration could be placed in a state of anergy or lymphocytic inefficient activity. Furthermore, the significant inverse correlation between CD163 tissue concentration and survival explains the relevance of this type of immune cell when creating a strong immunosuppressive environment. This information may potentially be used to support the selection of patients for immunotherapy.

Objetivos Evaluar los resultados de la prostatectomía radical asistida por robot (PRAR), y compararlos con los de la cirugía abierta (PRA) y laparoscópica (PRL). El interés no solo radica en los resultados oncológicos y funcionales de la serie, sino en la evaluación de la calidad de vida (QoL), la recuperación postoperatoria y la satisfacción personal de los pacientes con la intervención (PR), fundamentalmente. Métodos Se realizaron 685 PR en nuestro centro entre 2011-2018 (17,8% PRA, 22,2% PRL y 60% PRAR). Los pacientes fueron evaluados prospectivamente mediante seguimiento hasta abril de 2020, y con la realización un cuestionario múltiple a los 12 meses post-PR, que incluía ICIQ-SF, SHIM, IPSS, IQL y preguntas sobre el dolor, la recuperación postoperatoria y la satisfacción del paciente (SP). También se recogieron datos basales y postoperatorios relacionados con el paciente y el tratamiento, y se realizaron regresiones logísticas binomiales para las comparaciones 1 vs. 1 (PRA vs. PRAR y PRL vs. PRAR). Resultados Los pacientes tratados con PRAR tienen en general menos comorbilidades, menos agresividad tumoral, un requerimiento de mayor tiempo operatorio y un número mayor de márgenes quirúrgicos positivos que los pacientes tratados con PRA y PRL. Sin embargo, la PRAR supera a la PRA en: días de estancia hospitalaria (OR: 0,86; IC 95%: 0,80-0,94), disminución de hemoglobina (OR: 0,38; IC 95%: 0,30-0,47), tasas de transfusión (OR: 0,18; IC 95%: 0,09-0,34), complicaciones tempranas (p = 0,001), IQL (OR: 0,82; IC 95%: 0,69-0,98), función eréctil (OR: 0,41; IC 95%: 0,21-0,79), manejo del dolor (OR: 0,82; IC 95%: 0,75-0,89), recuperación postoperatoria (p < 0,001) y elección de un abordaje diferente (OR: 5,55; IC 95%: 3,14-9,80). La PRAR es superior a la PRL en: continencia urinaria (OR: 0,55; IC 95%: 0,37-0,82), IPSS (OR: 0,96; IC 95%: 0,93-0,98), IQL (OR: 0,76; IC 95%: 0,66-0,88), función eréctil (OR: 0,52; IC 95%: 0,29-0,93), recuperación posquirúrgica (p = 0,02 y 0,004), PS (p = 0,005; 0,002; y 0,03) y elección de un abordaje diferente (OR: 7,79; IC 95%: 4,63-13,13). Conclusiones Los hallazgos de nuestro estudio respaldan la efectividad de la PRAR sobre la PRL y/o la PRA de manera global, tanto en factores funcionales, como en la recuperación postoperatoria, la QoL y la PS. Los resultados oncológicos aún deben ser mejorados.

Due to the COVID19 pandemic, solutions to automate disinfection using UV-C combined with mobile robots are beginning to be explored. It has been proved that the use of these systems highly reduces the risk of contagion. However, its use in real applications is not being as rapid as it needs to be. One of the main market input barriers is the fear of degrading facilities. For this reason, it is crucial to perform a detailed study on the degradation effect of UV-C light on inert materials. This experimental study proves that, considering exposition times equivalent to several work years in hospital rooms, only the appearance of the material is affected, but not their mechanical functionalities. This relevant result could contribute to accelerate the deployment of these beneficial disinfection technologies. For that purpose, a colorimetry test, tensile strength test, and analysis of the surface microstructure were carried out. The results showed that polymers tend to turn yellow, while fabrics lose intensity depending on the color. Red is hardly affected by UV-C, but blue and green are. Thus, this study contributes to the identification of the best materials and colors to be used in rooms subjected to disinfection processes. In addition, it is shown how the surface microstructure of the materials is altered in most of the materials, but not the tensile strength of the fabrics.

Background:Severe cognitive decline is one of the major public health problems in developed countries. Finding modifiable risk factors could become essential to develop strategies to prevent or delay dementia progression and stop its rising incidence. Objective:Our aim was to investigate the association between hypertension and cognitive function and to assess whether better adherence to the Mediterranean diet may modify this association. Methods:A subsample of 764 participants from the 'Seguimiento Universidad de Navarra' (SUN) cohort older than 55 years was evaluated with the Spanish Telephone Interview for Cognitive Status (TICS-m) at two-time points, separated by 6 years. Multivariable-adjusted linear regression models were used to prospectively assess the association between hypertension -also according to adherence to the Mediterranean diet- and 6-y changes in cognitive function. Results:The adjusted between-group difference in the 6-year change of the TICS-m score between hypertensive participants and their non-hypertensive counterparts was -0.36 (95% CI -0.70, -0.02). This association was stronger among participants with a lower adherence to the Mediterranean diet [-0.62 (95% CI: -1.09, -0.15)] but the differences between hypertensive and non-hypertensive participants were no longer significant among participants with a higher baseline adherence to the Mediterranean diet. Conclusion:In this Mediterranean cohort, hypertension was inversely associated with cognitive function, but an attenuation of this detrimental association by a moderate/high adherence to the Mediterranean diet was suggested.

SARS-CoV-2 is responsible for the COVID-19 pandemic, which has caused almost 570 million infections and over six million deaths worldwide. To help curb its spread, solutions using ultraviolet light (UV) for quick virus inactivation inside buildings without human intervention could be very useful to reduce chances of contagion. The UV dose must be sufficient to inactivate the virus considering the different materials in the room, but it should not be too high, not to degrade the environment. In the present study, we have analyzed the ability of a 254nm wavelength UV-C lamp to inactivate dried samples of SARS-CoV-2 exposed at a distance of two meters, simulating a full-scale scenario. Our results showed that virus inactivation was extremely efficient in most tested materials, which included plastic, metal, wood, and textile, with a UV-C exposure of only 42s (equivalent to 10mJ/cm2). However, porous materials like medium density fibreboard, were hard to decontaminate, indicating that they should be avoided in hospital rooms and public places.

(1) Background: Patients with schizophrenia have higher mortality, with cardiovascular diseases being the first cause of mortality. This study aims to estimate the excess risk of hospital admission for cardiovascular events in schizophrenic patients, adjusting for comorbidity and risk factors. (2) Methods: The APNA study is a dynamic prospective cohort of all residents in Navarra, Spain. A total of 505,889 people over 18 years old were followed for five years. The endpoint was hospital admissions for a cardiovascular event. Direct Acyclic Graphs (DAG) and Cox regression were used. (3) Results: Schizophrenic patients had a Hazard Ratio (HR) of 1.414 (95% CI 1.031-1.938) of hospital admission for a cardiovascular event after adjusting for age, sex, hypertension, type 2 diabetes, dyslipidemia, smoking, low income, obesity, antecedents of cardiovascular disease, and smoking. In non-adherent to antipsychotic treatment schizophrenia patients, the HR was 2.232 (95% CI 1.267-3.933). (4) Conclusions: Patients with schizophrenia have a higher risk of hospital admission for cardiovascular events than persons with the same risk factors without schizophrenia. Primary care nursing interventions should monitor these patients and reduce cardiovascular risk factors.

Background and objective: We compared the efficacy and safety of standard vs. extended primary cytomegalovirus (CMV) prophylaxis in solid organ transplantation. Materials and methods: Retrospective cohort study of CMV seronegative recipients who received CMV prophylaxis after solid organ transplantation from seropositive donor (D+/R-) (2007-2017). CMV infection in the first two years after transplantation in recipients with prophylaxis longer or shorter than 100 days were compared. Results: CMV infection occurred in 29 of 66 patients (43.9%) with prophylaxis. Forty-five patients (68.2%) received extended prophylaxis. CMV infection and disease rates were not different between patients with extended and standard prophylaxis. However, extended prophylaxis was associated with a higher rate of myelotoxicity (68.9% vs. 42.9%, p<0.05). Conclusions: Extending primary CMV prophylaxis over 100 days did not prevent late-onset infection but it was associated with hematological toxicity.

Background: Stroke is the second largest single cause of death and disability in Latin America and the Caribbean (LAC). There have been large overall declines in stroke mortality rates in most LAC countries in recent decades. Objective: To analyze trends in mortality caused by stroke in LAC countries in the period 1979-2015. Methods: We extracted data for age-standardized stroke mortality rates per 100,000 in LAC for the period 1979-2015 from the World Health Organization Mortality Database. Joinpoint regression was used to analyze the trends and compute the annual percent change (APC) in LAC as a whole and by country. Analyses were conducted by gender, region and World Bank income classification. Results: Mortality from stroke has decreased in LAC over the study period by an average APC of -1.9%. Most countries showed significant downward trends, with the sharpest decreases in Chile, Colombia and Uruguay. We recorded statistically significant decreases of -1.4% and -2.4% in mortality rates in men and women, respectively, in the whole LAC. Southern and high-income countries showed the steepest decreases. Conclusions: Stroke mortality has decreased in LAC, in both sexes, especially in southern and high-income countries. Our results could serve as a reference for the development of primary prevention and acute management of stroke policies focused on countries with higher mortality.

Background: University students are a risk group for heavy substance use and the experience of various potentially severe negative substance use consequences which may impact on their health, social, and academic functioning. Whilst the experience of negative consequences of substance use is well understood in North American student samples, there is little data on these experiences in European students. In order to develop effective harm prevention and reduction interventions for students' substance use, there needs to be an understanding of the types of consequences experienced in European student samples. Objectives: The aim of the study was to investigate the prevalence and predictors of the experience of negative substance use-related consequences amongst university students in 7 European countries. Methods: University students (n = 4,482) in Belgium, Denmark, Germany, the Slovak Republic, Spain, Turkey, and the UK completed an online survey of their substance use behaviours and the experience of associated negative consequences. Results: European students reported that experiencing a hangover or illness, missing class, being short of money, and experiencing memory loss were the most commonly experienced negative consequences of substance use. Not living with other students and using alcohol, cannabis, sedatives, and cocaine were also associated with higher odds of experiencing these negative consequences. Conclusions: In contrast to North American data, European university students tended to experience consequences that are associated with lower level health risks rather than more severe consequences (e.g., drink-driving and physical injury). Harm prevention and reduction interventions for students should be targeted towards those consequences that are most salient to the target group to ensure feedback is relevant and potentially more effective in changing students' substance use behaviours.

Background Adoptive immunotherapy with tumour-infiltrating lymphocytes (TIL) may benefit from the use of selective markers, such as PD-1, for tumour-specific T-cell enrichment, and the identification of predictive factors that help identify those patients capable of rendering tumour-reactive TILs. We have investigated this in ovarian cancer (OC) patients as candidates for TIL therapy implementation. Methods PD-1(-) and PD-1(+) CD8 TILs were isolated from ovarian tumours and expanded cells were tested against autologous tumour cells. Baseline tumour samples were examined using flow cytometry, multiplexed immunofluorescence and Nanostring technology, for gene expression analyses, as well as a next-generation sequencing gene panel, for tumour mutational burden (TMB) calculation. Results Tumour-reactive TILs were detected in half of patients and were exclusively present in cells derived from the PD-1(+) fraction. Importantly, a high TIL density in the fresh tumour, the presence of CD137(+) cells within the PD-1(+)CD8(+) TIL subset and their location in the tumour epithelium, together with a baseline T-cell-inflamed genetic signature and/or a high TMB, are features that identify patients rendering tumour-reactive TIL products. Conclusion We have demonstrated that PD-1 identifies ovarian tumour-specific CD8 TILs and has uncovered predictive factors that identify OC patients who are likely to render tumour-specific cells from PD-1(+) TILs.

There is an impressive body of literature on risk communication relevant to the prevention and control of communicable diseases. This literature is complicated, however, by blurred definitions and overlap between risk communication and crisis communication. It is also widely dispersed across academic disciplines, lacking rigorous empirical evidence to demonstrate effectiveness, challenged by the complex and unpredictable ways that individuals perceive risk and the environmental, social, cultural and linguistic factors through which risk communication is viewed. At the European level, there is a need to bring the work on risk communication for communicable diseases together on many levels: Theoretical models of risk communication must be integrated across disciplines. The bridge between academic research and risk communication in practice needs to be strengthened (that is, findings of research need to be better communicated to end users and built into risk communication planning, guidance documents, training modules). Risk communicators should be collaborating more closely with community-level health providers and media. In addition, there is consensus in much of the literature reviewed on the need for coordinated leadership at the European level to ensure structured and systematic approaches to risk communication planning, preparedness and response. We have a clearer picture today than a decade ago about the requirements, parameters and challenges of communicating risks of co