Navarras Health Research Institute IdiSNA

Pamplona, Spain

Navarras Health Research Institute IdiSNA

Pamplona, Spain
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Pereira C.,Hospitalet Of Llobregat | Gimenez-Xavier P.,Hospitalet Of Llobregat | Pros E.,Hospitalet Of Llobregat | Pajares M.J.,University of Navarra | And 23 more authors.
Clinical Cancer Research | Year: 2017

Purpose: We aimed to maximize the performance of detecting genetic alterations in lung cancer using high-throughput sequencing for patient-derived xenografts (PDXs). Experimental Design: We undertook an integrated RNA and whole-exome sequencing of 14 PDXs. We focused on the genetic and functional analysis of β2-microglobulin (B2M), a component of the HLA class-I complex. Results: We identified alterations in genes involved in various functions, such as B2M involved in immunosurveillance. We extended the mutational analysis of B2M to about 230 lung cancers. Five percent of the lung cancers carried somatic mutations, most of which impaired the correct formation of the HLA-I complex. We also report that genes such as CALR, PDIA3, and TAP1, which are involved in the maturation of the HLA-I complex, are altered in lung cancer. By gene expression microarrays, we observed that restitution of B2M in lung cancer cells upregulated targets of IFNα/IFNγ. Furthermore, one third of the lung cancers lacked the HLA-I complex, which was associated with lower cytotoxic CD8+ lymphocyte infiltration. The levels of B2M and HLA-I proteins correlated with those of PD-L1. Finally, a deficiency in HLA-I complex and CD8+ infiltration tended to correlate with reduced survival of patients with lung cancer treated with anti-PD-1/anti-PD-L1. Conclusions: Here, we report recurrent inactivation of B2M in lung cancer. These observations, coupled with the mutations found at CALR, PDIA3, and TAP1, and the downregulation of the HLA-I complex, indicate that an abnormal immunosurveillance axis contributes to lung cancer development. Finally, our observations suggest that an impaired HLA-I complex affects the response to anti-PD-1/anti-PD-L1 therapies. ©2017 AACR.

De Deus Mendonca R.,Public University of Navarra | De Deus Mendonca R.,Federal University of Minas Gerais | De Deus Mendonca R.,CAPES Foundation | Souza Lopes A.C.,Federal University of Minas Gerais | And 12 more authors.
American Journal of Hypertension | Year: 2017

BACKGROUND Some available evidence suggests that high consumption of ultra-processed foods (UPFs) is associated with a higher risk of obesity. Collectively, this association and the nutritional characteristics of UPFs suggest that UPFs might also be associated with hypertension. METHODS We prospectively evaluated the relationship between UPF consumption and the risk of hypertension in a prospective Spanish cohort, the Seguimiento Universidad de Navarra project. We included 14,790 Spanish adult university graduates who were initially free of hypertension at baseline who were followed for a mean of 9.1 years (SD, 3.9 years; total personyears: 134,784). UPF (industrial formulations of chemical compounds which, beyond substances of common culinary use such as salt, sugar, oils, and fats, include substances also derived from foods but not used in culinary preparations) consumption was assessed using a validated semiquantitative 136-item food-frequency questionnaire. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% confdence intervals (CIs) for hypertension incidence. RESULTS During follow-up, 1,702 incident cases of hypertension were identifed. Participants in the highest tertile of UPF consumption had a higher risk of developing hypertension (adjusted HR, 1.21; 95% CI, 1.06, 1.37; P for trend = 0.004) than those in the lowest tertile after adjusting for potential confounders. CONCLUSIONS In this large prospective cohort of Spanish middle-aged adult university graduates, a positive association between UPF consumption and hypertension risk was observed. Additional longitudinal studies are needed to confrm our results. © 2017 American Journal of Hypertension, Ltd. All rights reserved.

Bes-Rastrollo M.,Public University of Navarra | Bes-Rastrollo M.,Navarras Health Research Institute IDISNA | Bes-Rastrollo M.,CIBER ISCIII | Sayon-Orea C.,Public University of Navarra | And 8 more authors.
Obesity | Year: 2016

Objective: To conduct a comprehensive literature review in the field of added-sugar consumption on weight gain including the effect of fructose-containing caloric sweeteners and sugar taxation. Methods: A search of three databases was conducted in the time period from the inception of the databases to August 2015. Sensitive search strategies were used in order to retrieve systematic reviews (SR) of fructose, sucrose, or sugar-sweetened beverages (SSBs) on weight gain and metabolic adverse effects, conducted on humans and written in English, Spanish, or French. In addition, a review about SSB taxation and weight outcomes was conducted. Results: The search yielded 24 SRs about SSBs and obesity, 23 SRs on fructose or SSBs and metabolic adverse effects, and 24 studies about SSB taxation and weight control. Conclusions: The majority of SRs, especially the most recent ones, with the highest quality and without any disclosed conflict of interest, suggested that the consumption of SSBs is a risk factor for obesity. The effect of fructose-containing caloric sweeteners, on weight gain is mediated by overconsumption of beverages with these sweeteners, leading to an extra provision of energy intake. The tax tool alone on added sugars appears insufficient to curb the obesity epidemic, but it needs to be included in a multicomponent structural strategy. © 2016 The Obesity Society

Centeno C.,University of Navarra | Centeno C.,Navarras Health Research Institute IDISNA | Lynch T.,European Association for Palliative Care EAPC | Garralda E.,University of Navarra | And 9 more authors.
Palliative Medicine | Year: 2016

Background: The evolution of the provision of palliative care specialised services is important for planning and evaluation. Aim: To examine the development between 2005 and 2012 of three specialised palliative care services across the World Health Organization European Region - home care teams, hospital support teams and inpatient palliative care services. Design and setting: Data were extracted and analysed from two editions of the European Association for Palliative Care Atlas of Palliative Care in Europe. Significant development of each type of services was demonstrated by adjusted residual analysis, ratio of services per population and 2012 coverage (relationship between provision of available services and demand services estimated to meet the palliative care needs of a population). For the measurement of palliative care coverage, we used European Association for Palliative Care White Paper recommendations: one home care team per 100,000 inhabitants, one hospital support team per 200,000 inhabitants and one inpatient palliative care service per 200,000 inhabitants. To estimate evolution at the supranational level, mean comparison between years and European sub-regions is presented. Results: Of 53 countries, 46 (87%) provided data. Europe has developed significant home care team, inpatient palliative care service and hospital support team in 2005-2012. The improvement was statistically significant for Western European countries, but not for Central and Eastern countries. Significant development in at least a type of services was in 21 of 46 (46%) countries. The estimations of 2012 coverage for inpatient palliative care service, home care team and hospital support team are 62%, 52% and 31% for Western European and 20%, 14% and 3% for Central and Eastern, respectively. Conclusion: Although there has been a positive development in overall palliative care coverage in Europe between 2005 and 2012, the services available in most countries are still insufficient to meet the palliative care needs of the population. © The Author(s) 2015.

Aldridge M.D.,Mount Sinai School of Medicine | Hasselaar J.,Radboud University Nijmegen | Garralda E.,University of Navarra | Garralda E.,Navarras Health Research Institute IDISNA | And 7 more authors.
Palliative Medicine | Year: 2016

Background: Early integration of palliative care into the management of patients with serious disease has the potential to both improve quality of life of patients and families and reduce healthcare costs. Despite these benefits, significant barriers exist in the United States to the early integration of palliative care in the disease trajectory of individuals with serious illness. Aim: To provide an overview of the barriers to more widespread palliative care integration in the United States. Design and data sources: A literature review using PubMed from 2005 to March 2015 augmented by primary data collected from 405 hospitals included in the Center to Advance Palliative Care's National Palliative Care Registry for years 2012 and 2013. We use the World Health Organization's Public Health Strategy for Palliative Care as a framework for analyzing barriers to palliative care integration. Results: We identified key barriers to palliative care integration across three World Health Organization domains: (1) education domain: lack of adequate education/training and perception of palliative care as end-of-life care; (2) implementation domain: inadequate size of palliative medicine-trained workforce, challenge of identifying patients appropriate for palliative care referral, and need for culture change across settings; (3) policy domain: fragmented healthcare system, need for greater funding for research, lack of adequate reimbursement for palliative care, and regulatory barriers. Conclusion: We describe the key policy and educational opportunities in the United States to address and potentially overcome the barriers to greater integration of palliative care into the healthcare of Americans with serious illness. © SAGE Publications.

Allende M.,Navarras Health Research Institute IdiSNA | Molina E.,Navarras Health Research Institute IdiSNA | Gonzalez-Porras J.R.,Hospital Universitario Of Salamanca | Toledo E.,Public University of Navarra | And 2 more authors.
Stroke | Year: 2016

Background and Purpose-The risk of cardioembolic stroke in patients with atrial fibrillation (AF) cannot be accurately assessed and novel tools are needed to improve prediction. We hypothesize that telomere shortening constitutes a novel risk factor for cardioembolic stroke in patients with AF. Methods-The peripheral blood leukocyte telomere length (LTL) was determined by real-time polymerase chain reaction in 187 patients with AF, 93 of them without stroke history and 94 of them having suffered 1 cardioembolic stroke. Percentiles were calculated according to LTL values in the nonstroke group to estimate the cardioembolic stroke risk associated with LTL using logistic regression models. Results-Short LTL values were independently and dose-dependently associated with an increased risk of cardioembolic stroke, with an odds ratio (95% confidence interval) of 2.93 (1.24-6.94) and 6.26 (2.01-19.52), respectively, for sex, hypertension, diabetes mellitus, heart failure, and age-adjusted models using the LTL 10th and 5th percentile cut-offs, respectively. Conclusions-Telomere shortening is associated with cardioembolic stroke risk in patients with AF. Prospective studies are encouraged to establish the value of LTL to improve prediction tools to categorize cardioembolic stroke risk in AF. © 2016 American Heart Association, Inc.

Velez-Galarraga R.,University of Navarra | Guillen-Grima F.,University of Navarra | Guillen-Grima F.,Navarras Health Research Institute IDISNA | Guillen-Grima F.,Public University of Navarra | And 3 more authors.
European Journal of Paediatric Neurology | Year: 2016

Objectives To determine the prevalence of sleep disorders in children with attention-deficit/hyperactivity disorder (ADHD) and in a control population. To examine the relationship between sleep disorders and symptoms of inattention, hyperactivity/impulsiveness and executive dysfunction. Materials and methods We studied 126 children with ADHD and 1036 control children aged between 5 and 18 years old. Caregivers completed the Pediatric Sleep Questionnaire and the ADHD Rating Scale (ADHD-RS). Children with ADHD were subsequently assessed for executive function with the Conner's Continuous Performance Test (CPT) or with AULA Nesplora. Results Children with ADHD slept less at night and were more likely to display sleep-related rhythmic movements. Children in the ADHD group who were under 12 years old and who had total ADHD-RS scores over the 90th percentile had more difficulty falling asleep than other children; there was also a relationship between total ADHD-RS scores over the 90th percentile and certain parasomnias in the control population. There was a correlation between shorter duration of night-time sleep and omission errors in children who were 12 or older and who were under pharmacological treatment for ADHD. Bedtime resistance and difficulty falling sleep were more frequent in children with ADHD whose symptoms were not treated pharmacologically, than in children receiving treatment. Interpretation Symptoms of inattention and hyperactivity are correlated with impaired sleep duration and quality; specifically, there is an association between ADHD symptoms and problems falling asleep and parasomnias, however, the current study does not address the nature and direction of causality. Children with ADHD and receiving methylphenidate had fewer sleep disorders, suggesting that, at least in some children, stimulant treatment is associated with improvement of some aspects of sleep. Shorter sleep duration in adolescents under pharmacological treatment for ADHD tended to result in more errors of omission, suggesting that it is important to promote good sleep habits in this population. © 2016 European Paediatric Neurology Society

Gonzalez-Muniesa P.,University of Navarra | Gonzalez-Muniesa P.,Institute Salud Carlos III | Gonzalez-Muniesa P.,Navarras Health Research Institute IDISNA | Garcia-Gerique L.,University of Navarra | And 6 more authors.
Oxidative Medicine and Cellular Longevity | Year: 2016

Several studies have shown a pathological oxygenation (hypoxia/hyperoxia) on the adipose tissue in obese subjects. Additionally, the excess of body weight is often accompanied by a state of chronic low-degree inflammation. The inflammation phenomenon is a complex biological response mounted by tissues to combat injurious stimuli in order to maintain cell homeostasis. Furthermore, it is believed that the abnormal oxygen partial pressure occurring in adipose tissue is involved in triggering inflammatory processes. In this context, oxygen is used in modern medicine as a treatment for several diseases with inflammatory components. Thus, hyperbaric oxygenation has demonstrated beneficial effects, apart from improving local tissue oxygenation, on promoting angiogenesis, wound healing, providing neuroprotection, facilitating glucose uptake, appetite, and others. Nevertheless, an excessive hyperoxia exposure can lead to deleterious effects such as oxidative stress, pulmonary edema, and maybe inflammation. Interestingly, some of these favorable outcomes occur under high and low oxygen concentrations. Hereby, we review a potential therapeutic approach to the management of obesity as well as the oxygen-related inflammation accompanying expanded adipose tissue, based on elevated oxygen concentrations. To conclude, we highlight at the end of this review some areas that need further clarification. © 2016 Pedro González-Muniesa et al.

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