Monitoring vascular normalization induced by antiangiogenic treatment with (18)F-fluoromisonidazole-PET

This work was supported by the following sources: Fondo de Investigacion Sanitaria (Ministry of Health, Spain; numbers FIS PI10/0288, FIS PI13/00430, FIS PI 11/00616, CPII14/00005 and FIS PI14/00860; the first two awarded to MQF and the last three to MD), and "Fondo Europeo de Desarrollo Regional (FEDER) - Una manera de hacer Europa". MQF is a recipient of a 2010 Beca-Retorno from the AECC Scientific Foundation. Rosae Foundation and AVON Espana S.A.U. contributed to this work with unrestricted donations. Dovitinib was kindly provided by Novartis.BACKGROUND: Rationalization of antiangiogenics requires biomarkers. Vascular re-normalization is one widely accepted mechanism of action for this drug class. The interstitium of tumors with abnormal vasculature is hypoxic. We sought to track vascular normalization with (18)F-misonidazole ([18F]-FMISO, a probe that detects hypoxia) PET, in response to window-of-opportunity (WoO) treatment with the antiangiogenic dovitinib. METHODS: Two patient-derived pancreas xenografts (PDXs; Panc215 and Panc286) and the spontaneous breast cancer model MMTV-PyMT were used. Animals were treated during 1 week of WoO treatment with vehicle or dovitinib, preceded and followed by [18F]-FMISO-PET, [18F]-FDG-PET, and histologic assessment (dextran extravasation, hypoxia and microvessel staining, and necrosis, cleaved caspase-3 and Ki67 measurements). After WoO treatment, gemcitabine (pancreas)/adriamycin (breast) or vehicle was added and animals were treated until the humane endpoint. Tumor growth inhibition (TGI) and survival were the parameters studied. RESULTS: [18F]-FMISO SUV did not change after dovitinib-WoO treatment compared to vehicle-WoO (0.54 vs. 0.6) treatment in Panc215, but it decreased significantly in Panc286 (0.58 vs. 1.18; P < 0.05). In parallel, 10-KDa perivascular dextran extravasation was not reduced with dovitinib or vehicle-WoO treatment in Panc215, but it was reduced in Panc286. Whereas the addition of dovitinib to gemcitabine was indifferent in Panc215, it increased TGI in Panc286 (TGI switched from -59% to +49%). [18F]-FMISO SUV changes were accompanied by an almost 100% increase in interstitial gemcitabine delivery (665-1260 ng/mL). The results were validated in the PyMT model. CONCLUSIONS: [18F]-FMISO accurately monitored vascular re-normalization and improved interstitial chemotherapy delivery.This work was supported by the following sources: Fondo de Investigacion Sanitaria (Ministry of Health, Spain; numbers FIS PI10/0288, FIS PI13/00430, FIS PI 11/00616, CPII14/00005 and FIS PI14/00860; the first two awarded to MQF and the last three to MD), and "Fondo Europeo de Desarrollo Regional (FEDER) - Una manera de hacer Europa". MQF is a recipient of a 2010 Beca-Retorno from the AECC Scientific Foundation. Rosae Foundation and AVON Espana S.A.U. contributed to this work with unrestricted donations. Dovitinib was kindly provided by Novartis.S

Informe de situación: Actividad gripal en la temporada 2018-19 Evaluación de riesgo hasta semana 03/2019

[ES] La epidemia gripal 2018-19 se ha iniciado en España en la semana 01/2019, tres semanas más tarde que en las dos temporadas previas, pero en el rango de las temporadas post-pandémicas previas. La incidencia de gripe se asocia de forma casi exclusiva a la circulación de virus de la gripe tipo A. Aunque la proporción entre subtipos A(H1N1)pdm09 y A(H3N2) es similar, la tendencia de las últimas semanas indica un aumento en la proporción del primero. Los datos de vigilancia en hospitales señalan una distribución similar por tipo/subtipo de virus. Si bien el grupo de mayores de 65 años es el mayoritario (53%), este porcentaje es inferior al que se puede observar en aquellas temporadas en las que predomina A(H3N2) y se parece más a aquellas temporadas en las que predominó A(H1N1)pdm09. Hasta el momento, la epidemia gripal 2018-19 presenta un nivel bajo de transmisibilidad en todos los grupos de edad. El impacto ocasionado en la población española se estima medio, en términos de tasa de hospitalización y bajo en términos de excesos de mortalidad por todas las causas. Ambos indicadores, así como la gravedad clínica de la enfermedad, se seguirán evaluando en las semanas próximas de la epidemia gripal. Las estimaciones preliminares de EV antigripal de esta temporada en Canadá señalan un valor de EV frente a A(H1N1)pdm09 por encima del 70%, en consonancia con datos preliminares de la red Europea I-MOVE. La EV antigripal frente a A(H3N2) es subóptima hasta el momento. Sin embargo, se han estimado valores moderados de EV antigripal frente a todos los virus A en grupos recomendados de vacunación, lo que refuerza la recomendación oficial de vacunación antigripal en estos grupos de riesgo de complicaciones por gripe. En definitiva, las características de la epidemia 2018-19 hasta el momento se mueven en un patrón intermedio entre las temporadas de A(H1N1)pdm09 y las de A(H3N2), de forma que según derive la circulación mayoritaria de uno u otro virus, cabe esperar que predominen unas u otras características. [EN] Influenza activity in Spain started this 2018-19 season in week 01/2019, three weeks later than in the previous two seasons, but in the range of the previous post-pandemic seasons. So far, the influenza season 2018-19 is characterized by the predominant circulation of type A. Although both A(H1N1) pdm09 and A(H3N2) subtypes are co-circulating in similar proportions, the trend of the last weeks indicates an increase in the proportion of the first. Surveillance data in hospitals indicate a similar distribution by type/subtype. Although 53% were adults 65 years of age and older, this percentage is lower than that observed in seasons associated with A(H3N2) predominance, and more similar to those seasons in which A(H1N1)pdm09 predominated. So far, the influenza season 2018-19 has a low level of transmissibility in all age groups. The impact caused in the Spanish population is estimated as “medium”, in terms of hospitalization rates, and “low” in terms of all causes excess mortality. Both indicators, as well as the clinical severity of the disease, will continue to be evaluated in the next few weeks of the flu epidemic. Preliminary estimates of the effectiveness of influenza vaccine this season in Canada indicate good vaccine effectiveness (VE) (above 70%), in line with preliminary data from the European I-MOVE network. The VE against influenza A(H3N2) viruses is suboptimal so far. However, moderate values of VE have been estimated against all A viruses in recommended groups of vaccination, which reinforces the official recommendation of influenza vaccination in these risk groups of complications due to influenza. In short, the characteristics of the influenza season 2018-19 so far move in an intermediate pattern between the A(H1N1)pdm09 seasons and those with A(H3N2) predominance. It is expected that some or other characteristics will prevail depending on the predominance of the circulation of one or the other virus.N

Evaluating the Applicability of Data-Driven Dietary Patterns to Independent Samples with a Focus on Measurement Tools for Pattern Similarity

BACKGROUND: Diet is a key modifiable risk for many chronic diseases, but it remains unclear whether dietary patterns from one study sample are generalizable to other independent populations. OBJECTIVE: The primary objective of this study was to assess whether data-driven dietary patterns from one study sample are applicable to other populations. The secondary objective was to assess the validity of two criteria of pattern similarity. METHODS: Six dietary patterns-Western (n=3), Mediterranean, Prudent, and Healthy- from three published studies on breast cancer were reconstructed in a case-control study of 973 breast cancer patients and 973 controls. Three more internal patterns (Western, Prudent, and Mediterranean) were derived from this case-control study's own data. STATISTICAL ANALYSIS: Applicability was assessed by comparing the six reconstructed patterns with the three internal dietary patterns, using the congruence coefficient (CC) between pattern loadings. In cases where any pair met either of two commonly used criteria for declaring patterns similar (CC ≥0.85 or a statistically significant [P0.9) to their corresponding dietary pattern derived from the case-control study's data. Similar associations with risk for breast cancer were found in all pairs of dietary patterns that had high CC but not in all pairs of dietary patterns with statistically significant correlations. CONCLUSIONS: Similar dietary patterns can be found in independent samples. The P value of a correlation coefficient is less reliable than the CC as a criterion for declaring two dietary patterns similar. This study shows that diet scores based on a particular study are generalizable to other populations.This study was funded by Fundación Científica Asociación Española Contra el Cáncer (Scientific Foundation of the Spanish Association Against Cancer), the Spanish Ministry of Economy and Competitiveness (IJCI-2014-20900); Fundación Cerveza y Salud 2005 (Beer and Health Foundation 2005), Sociedad Española de Oncología Médica (Spanish Society of Medical Oncology), Federación de Mujeres con Cáncer de Mama (Association of Women with Breast Cancer) (EPY 1169-10 grant) and Association of Women with Breast Cancer from Elche (EPY 1394/15 grant)

Bioética. El final de la vida y las voluntades anticipadas

Esta obra contiene textos elaborados por investigadores de diferentes áreas del conocimiento: medicina, filosofía, derecho, entre otras especialidades, pertenecientes a distintos países: España, Chile y México. El objetivo principal de este libro es servir de referente teórico a otros investigadores de bioética, y especialmente a los que son o desean estar especializados en la comprensión del final de la vida y las voluntades anticipadas en el ámbito sanitario en cualquier país del mundo

Vigilancia de la gripe en España Temporada 2015-2016 (desde la semana 40/2015 hasta la semana 20/2016)

[ES] La actividad gripal en España en la temporada 2015-16 fue baja y asociada a una circulación mayoritaria de virus de la gripe A(H1N1)pdm09, con una creciente contribución de virus de la gripe B a medida que ha ido avanzando la temporada. La epidemia gripal se inició de forma tardía, presentando posteriormente una onda epidémica atípica, con una meseta de incidencia de gripe estable durante varias semanas consecutivas y una duración total en el rango de las 10 temporadas previas. Los menores de 15 años fueron el grupo de edad más afectado, con mayores tasas de incidencia acumulada en el grupo de 0-4 años. Se notificaron 12 brotes confirmados de gripe en siete CCAA. El 92% de los brotes se asoció a virus tipo A (siete A(H1N1)pdm09, 3 ANS y uno A(H3N2)) todos ellos en centros sanitarios, geriátricos o instituciones de larga estancia. De las 2.716 detecciones centinela identificadas a lo largo de la temporada, el 66% fueron virus de la gripe A, 98% de A(H1N1)pdm09, entre los subtipados. A nivel global se puede distinguir una primera onda de circulación de virus A(H1N1)pdm09 y posteriormente otra con circulación de virus B. En las redes centinela con picos de intensidad gripal más tempranos se ha observado una mayor contribución de virus A(H1N1)pdm09, mientras que en aquellas con periodos epidémicos más tardíos se observó una mayor contribución de virus B. La caracterización genética de los virus circulantes esta temporada indicó que todos aquellos virus A(H1N1) caracterizados eran semejantes a A/SouthAfrica/3626/2013, todos los virus A(H3N2) eran semejantes a A/HongKong/4801/2014 y la práctica totalidad (96%) de virus de la gripe B eran semejantes a B/Brisbane/60/2008 (linaje Victoria). Se notificaron 3.101 casos graves hospitalizados confirmados de gripe (CGHCG) en 19 CCAA, de los que 1.071 (35%) fueron admitidos en UCI y 352 (11,4%) fallecieron. La mayor proporción de casos se concentró en los mayores de 64 años (40%), seguido del grupo de 45-64 años (33%). Las mayores tasas de hospitalización se observaron en los mayores de 64 años y en el grupo de 0 a 4 años. En el 85% de los casos se confirmó el virus de la gripe tipo A, siendo el 98% de los subtipados (H1N1)pdm09. El 75% de los CGHCG presentó algún factor de riesgo de complicaciones de gripe. El 64,5% de los pacientes pertenecientes a grupos donde estaba recomendada la vacunación, no habían recibido la vacuna antigripal de esta temporada. Las defunciones en casos graves hospitalizados confirmados de gripe se concentraron fundamentalmente en los mayores de 64 años (59%) y el 88% de los casos fatales presentó algún factor de riesgo de complicaciones. El 59% de los pacientes recomendados de vacunación no habían recibido la vacuna antigripal de esta temporada. La letalidad observada en términos de defunciones entre CGHCG fue inferior a la temporada previa, y similar a las anteriores. El sistema MOMO (Monitorización de la mortalidad diaria) estimó un exceso de mortalidad por todas las causas en las semanas 9, 11, 13 y 14/2016 que se concentró en el grupo de 15 a 64 años. Excesos similares se han informado en varios países europeos. [EN] Influenza activity in Spain during the 2015-16 season was low and dominated by influenza A(H1N1)pdm09 virus circulation, with an increasing contribution from B virus as the season progressed. Influenza epidemic had a late time presentation, showing an atypical epidemic wave afterwards, with a stable incidence plateau for several consecutive weeks. The total duration was in the range of the previous 10 seasons. Children under 15 years old have been the most affected with higher rates of cumulative incidence in 0-4 age group. Twelve laboratory-confirmed influenza outbreaks were reported in seven autonomous regions (AR), 92% of them associated with type A virus (seven A(H1N1)pdm09, 3 A not subtyped and one A (H3N2), all in health centers, nursing homes or long-stay institutions. Of the 2,716 specimens from sentinel sources tested positive for influenza virus throughout the season, 66% were influenza A virus, with A(H1N1)pdm09 representing 98% of those subtyped. Globally, a first wave associated with A(H1N1)pdm09 can be distinguished, and then another associated with B virus. In those sentinel networks with early intensity peak, a greater contribution of virus A (H1N1) pdm09 has been observed, while those with later epidemic periods where associated with greater contribution of B virus. All A(H1N1)pdm09 virus genetically characterized have been similar to A/ SouthAfrica/3626/2013, all A(H3N2) were similar to A/HongKong/4801/2014 and almost all (96%) of influenza B viruses were similar to B/Brisban /60/2008 (Victoria lineage). A total of 3,101 severe hospitalized laboratory-confirmed influenza cases (SHCIC) were reported in 19 AR, of which 1,071 (35%) were admitted to ICU and 352 (11.4%) died. The highest percentage of SHCIC occurred over 64 years (40%), followed by the 45-64 age group (33%). The highest hospitalization rates were observed over 64 years and in the group of 0-4 years. The 85% of SHCIC were associated with influenza A virus, and the vast majority of the subtyped A viruses (98%) were A(H1N1)pdm09. Seventy-five percent had underlying conditions and 64.5% had not received a seasonal influenza vaccine. Most of the deaths of SHCIC (59%) were in adults over 64 years old. Eighty-eight percent had underlying conditions and 59% of patients with recommended vaccination condition had not received a seasonal influenza vaccine. MOMO system (Monitoring daily mortality) estimated an excess mortality from all causes in weeks 9, 11, 13 and 14/2016 which focused on the group of 15-64 years. Similar excesses have been reported in several European countrie

Dietary diversity and nutritional adequacy among an older Spanish population with metabolic syndrome in the PREDIMED-Plus study: a cross-sectional analysis

Dietary guidelines emphasize the importance of a varied diet to provide an adequate nutrient intake. However, an older age is often associated with consumption of monotonous diets that can be nutritionally inadequate, increasing the risk for the development or progression of diet-related chronic diseases, such as metabolic syndrome (MetS). To assess the association between dietary diversity (DD) and nutrient intake adequacy and to identify demographic variables associated with DD, we cross-sectionally analyzed baseline data from the PREDIMED-Plus trial: 6587 Spanish adults aged 55-75 years, with overweight/obesity who also had MetS. An energy-adjusted dietary diversity score (DDS) was calculated using a 143-item validated semi-quantitative food frequency questionnaire (FFQ). Nutrient inadequacy was defined as an intake below 2/3 of the dietary reference intake (DRI) forat least four of 17 nutrients proposed by the Institute of Medicine (IOM). Logistic regression models were used to evaluate the association between DDS and the risk of nutritionally inadequate intakes. In the higher DDS quartile there were more women and less current smokers. Compared with subjects in the highest DDS quartile, those in the lowest DDS quartile had a higher risk of inadequate nutrient intake: odds ratio (OR) = 28.56 (95% confidence interval (CI) 20.80-39.21). When we estimated food varietyfor each of the food groups, participants in the lowest quartile had a higher risk of inadequate nutrient intake for the groups of vegetables, OR = 14.03 (95% CI 10.55-18.65), fruits OR = 11.62 (95% CI 6.81-19.81), dairy products OR = 6.54 (95% CI 4.64-9.22) and protein foods OR = 6.60 (95% CI 1.96-22.24). As DDS decreased, the risk of inadequate nutrients intake rose. Given the impact of nutrient intake adequacy on the prevention of non-communicable diseases, health policies should focus on the promotion of a healthy varied diet, specifically promoting the intake of vegetables and fruit among population groups with lower DDS such as men, smokers or widow(er)s

Ultra-processed foods consumption as a promoting factor of greenhouse gas emissions, water, energy, and land use: A longitudinal assessment

Background: Dietary patterns can produce an environmental impact. Changes in people's diet, such as the increased consumption of ultra-processed food (UPF) can not only influence human health but also environment sustainability. Objectives: Assessment of the impact of 2-year changes in UPF consumption on greenhouse gas emissions and water, energy and land use. Design: A 2-year longitudinal study after a dietary intervention including 5879 participants from a Southern European population between the ages of 55-75 years with metabolic syndrome. Methods: Food intake was assessed using a validated 143-item food frequency questionnaire, which allowed classifying foods according to the NOVA system. In addition, sociodemographic data, Mediterranean diet adherence, and physical activity were obtained from validated questionnaires. Greenhouse gas emissions, water, energy and land use were calculated by means of the Agribalyse® 3.0.1 database of environmental impact indicators for food items. Changes in UPF consumption during a 2-year period were analyzed. Statistical analyses were conducted using computed General Linear Models. Results: Participants with major reductions in their UPF consumption reduced their impact by -0.6 kg of CO2eq and -5.3 MJ of energy. Water use was the only factor that increased as the percentage of UPF was reduced. Conclusions: Low consumption of ultra-processed foods may contribute to environmental sustainability. The processing level of the consumed food should be considered not only for nutritional advice on health but also for environmental protection

Development and evaluation of a machine learning-based in-hospital COVID-19 disease outcome predictor (CODOP): A multicontinental retrospective study

New SARS-CoV-2 variants, breakthrough infections, waning immunity, and sub-optimal vaccination rates account for surges of hospitalizations and deaths. There is an urgent need for clinically valuable and generalizable triage tools assisting the allocation of hospital resources, particularly in resource-limited countries. We developed and validate CODOP, a machine learning-based tool for predicting the clinical outcome of hospitalized COVID-19 patients. CODOP was trained, tested and validated with six cohorts encompassing 29223 COVID-19 patients from more than 150 hospitals in Spain, the USA and Latin America during 2020-22. CODOP uses 12 clinical parameters commonly measured at hospital admission for reaching high discriminative ability up to 9 days before clinical resolution (AUROC: 0.90-0.96), it is well calibrated, and it enables an effective dynamic risk stratification during hospitalization. Furthermore, CODOP maintains its predictive ability independently of the virus variant and the vaccination status. To reckon with the fluctuating pressure levels in hospitals during the pandemic, we offer two online CODOP calculators, suited for undertriage or overtriage scenarios, validated with a cohort of patients from 42 hospitals in three Latin American countries (78-100% sensitivity and 89-97% specificity). The performance of CODOP in heterogeneous and geographically disperse patient cohorts and the easiness of use strongly suggest its clinical utility, particularly in resource-limited countries