Research activity and capability in the European reference network MetabERN

BACKGROUND: MetabERN is one of the 24 European Reference Networks created according to the European Union directive 2011/24/EU on patient's rights in cross border healthcare. MetabERN associates 69 centres in 18 countries, which provide care for patients with Hereditary Metabolic Diseases, and have the mission to reinforce research and provide training for health professionals in this field. MetabERN performed a survey in December 2017 with the aim to produce an overview documenting research activities and potentials within the network. As the centres are multidisciplinary, separated questionnaires were sent to the clinical, university and laboratory teams. Answers were received from 52 out of the 69 centres of the network, covering 16 countries. A descriptive analysis of the information collected is presented. RESULTS: The answers indicate a marked interest of the respondents for research, who expressed high motivation and commitment, and estimated that the conditions to do research in their institution were mostly satisfactory. They are active in research, which according to several indicators, is competitive and satisfies standards of excellence, as well as the education programs offered in the respondent's universities. Research in the centres is primarily performed in genetics, pathophysiology, and epidemiology, and focuses on issues related to diagnosis. Few respondents declared having activity in human and social sciences, including research on patient's quality of life, patient's awareness, or methods for social support. Infrastructures offering services for medical research were rarely known and used by respondents, including national and international biobanking platforms. In contrast, respondents often participate to patient registries, even beyond their specific field of interest. CONCLUSIONS: Taken as a whole, these results provide an encouraging picture of the research capacities and activities in the MetabERN network, which, with respect to the number and representativeness of the investigated centres, gives a comprehensive picture of research on Hereditary Metabolic Diseases in Europe, as well as the priorities for future actions. Marginal activity in human and social sciences points out the limited multidisciplinary constitution of the responding teams with possible consequences on their current capability to participate to patient's empowerment programs and efficiently collaborate with patient's advocacy groups

Ophthalmology

PURPOSE: To investigate systemic and ocular determinants of peripapillary retinal nerve fiber layer thickness (pRNFLT) in the European population. DESIGN: Cross-sectional meta-analysis. PARTICIPANTS: A total of 16 084 European adults from 8 cohort studies (mean age range, 56.9+/-12.3-82.1+/-4.2 years) of the European Eye Epidemiology (E3) consortium. METHODS: We examined associations with pRNFLT measured by spectral-domain OCT in each study using multivariable linear regression and pooled results using random effects meta-analysis. MAIN OUTCOME MEASURES: Determinants of pRNFLT. RESULTS: Mean pRNFLT ranged from 86.8+/-21.4 mum in the Rotterdam Study I to 104.7+/-12.5 mum in the Rotterdam Study III. We found the following factors to be associated with reduced pRNFLT: Older age (beta = -0.38 mum/year; 95% confidence interval [CI], -0.57 to -0.18), higher intraocular pressure (IOP) (beta = -0.36 mum/mmHg; 95% CI, -0.56 to -0.15), visual impairment (beta = -5.50 mum; 95% CI, -9.37 to -1.64), and history of systemic hypertension (beta = -0.54 mum; 95% CI, -1.01 to -0.07) and stroke (beta = -1.94 mum; 95% CI, -3.17 to -0.72). A suggestive, albeit nonsignificant, association was observed for dementia (beta = -3.11 mum; 95% CI, -6.22 to 0.01). Higher pRNFLT was associated with more hyperopic spherical equivalent (beta = 1.39 mum/diopter; 95% CI, 1.19-1.59) and smoking (beta = 1.53 mum; 95% CI, 1.00-2.06 for current smokers compared with never-smokers). CONCLUSIONS: In addition to previously described determinants such as age and refraction, we found that systemic vascular and neurovascular diseases were associated with reduced pRNFLT. These may be of clinical relevance, especially in glaucoma monitoring of patients with newly occurring vascular comorbidities

Prevalence of Age-Related Macular Degeneration in Europe: The Past and the Future

Purpose Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. Design Meta-analysis of prevalence data. Participants A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe. Methods AMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA) was compared between late AMD subtypes; geographic atrophy (GA) and choroidal neovascularization (CNV). Main Outcome Measures Prevalence of early and late AMD, BCVA, and number of AMD cases. Results Prevalence of early AMD increased from 3.5% (95% confidence interval [CI] 2.1%–5.0%) in those aged 55–59 years to 17.6% (95%

Evaluation of the binding of four anti-tumor Casiopeinas to human serum albumin

The metal complexes designated by Casiopeinas (R) are mixed-ligand Cu-II-compounds some of them having promising antineoplastic properties. We report studies of binding of Cu(glycinato)(4,7-dimethyl-1,10-phenanthroline) (Cas-II-Gly (1)), Cu(acetylacetonato)(4,7-dimethy1-1,10-phenanthroline) (Cas-III-Ea (2)), Cu(glycinato) (4,4'-dimethyl-2,2'-bipyridine) (Cas-W-Gly (3)) and Cu(acetylacetonato)(4,4'-dimethyl-2,2'-bipyridine) (Cas-IIIia (4)) to human serum albumin (HSA) by circular dichroism (CD), Electron paramagnetic resonance (EPR) and fluorescence spectroscopy. The results indicate that HSA may bind up to three molecules of the tested Casiopeinas. This is confirmed by inductively coupled plasma atomic absorption spectroscopy measurements of samples of HSA-Casiopeinas after passing by adequate size-exclusion columns. The binding of Cas-II-Gly to HSA was also confirmed by MALDI-TOF mass spectrometric experiments. In the physiological range of concentrations the Casiopeinas form 1:1 adducts with HSA, with conditional binding constants of ca. 1 x 10(9) (1), 4 x 10(7) (2), 1 x 10(6) (3) and 2 x 10(5) (4), values determined from the CD spectra measured, and the fluorescence emission spectra indicates that the binding takes place close to the Trp214 residue. Overall, the data confirm that these Casiopeinas may bind to HSA and may be transported in blood serum by this protein; this might allow some selective tumor targeting, particularly in the case of Cas-Il-Gly. In this work we also discuss aspects associated to the reliability of the frequently used methodologies to determine binding constants based on the measurement of fluorescence emission spectra of solutions containing low concentrations of proteins such as HSA and BSA, by titration with solutions of metal complexes.programme Investigador FCT [IF/00100/2013, IF/00007/2015]CONACYT 171991, MexicoBiological Mass Spectrometry Isabel MouraUCIBIOUnidade de Ciencias Biomoleculares Aplicadas [UID/Multi/04378/2013]ERDF under the Partnership Agreement [POCI-01-0145-FEDER-007728]Associate Laboratory for Green Chemistry LAQV [UID/QUI/50006/2013]ERDF under the PT Partnership Agreement [POCI-01-0145-FEDER-007265

An epidemiological evaluation of the prevalence of malnutrition in Spanish patients with locally advanced or metastatic cancer.

OBJECTIVE: Malnutrition is frequent in cancer. The objective of this study was to determine the prevalence, in Spain, of malnutrition in cancer patients with advanced disease and to assess the therapeutic focus. METHODS: A total of 781 patients were evaluated to determine individual nutritional status using the Scored Patient Generated-Subjective Global Assessment (Scored PG-SGA) questionnaire. Almost 60% of the patients included were receiving cancer treatment. RESULTS: Patients with the highest weight loss were those with tumours of oesophagus (57%), stomach (50%) and larynx (47%). Serious eating problems were encountered by 68% of the patients; the principal problem being anorexia (42.2%). The median number of symptoms impeding food intake was 2. According to the Scored PG-SGA, 52% of the patients were moderately or severely malnourished and 97.6% required some form of nutritional intervention/recommendation. CONCLUSIONS: (a) the majority of patients in the study needed nutritional intervention; (b) more than 50% had moderate or severe malnutrition; (c) the Scored PG-SGA is a useful and simple tool for evaluating nutritional status and contains additional information on nutritional recommendations; (d) nutritional evaluation of the cancer patients needs to be improved so as to offer better treatment of symptoms and to improve the patient's quality of life

The European Eye Epidemiology spectral-domain optical coherence tomography classification of macular diseases for epidemiological studies

\u3cp\u3ePurpose: The aim of the European Eye Epidemiology (E3) consortium was to develop a spectral-domain optical coherence tomography (SD-OCT)-based classification for macular diseases to standardize epidemiological studies. Methods: A European panel of vitreoretinal disease experts and epidemiologists belonging to the E3 consortium was assembled to define a classification for SD-OCT imaging of the macula. A series of meeting was organized, to develop, test and finalize the classification. First, grading methods used by the different research groups were presented and discussed, and a first version of classification was proposed. This first version was then tested on a set of 50 SD-OCT images in the Bordeaux and Rotterdam centres. Agreements were analysed and discussed with the panel of experts and a final version of the classification was produced. Results: Definitions and classifications are proposed for the structure assessment of the vitreomacular interface (visibility of vitreous interface, vitreomacular adhesion, vitreomacular traction, epiretinal membrane, full-thickness macular hole, lamellar macular hole, macular pseudo-hole) and of the retina (retinoschisis, drusen, pigment epithelium detachment, hyper-reflective clumps, retinal pigment epithelium atrophy, intraretinal cystoid spaces, intraretinal tubular changes, subretinal fluid, subretinal material). Classifications according to size and location are defined. Illustrations of each item are provided, as well as the grading form. Conclusion: The E3 SD-OCT classification has been developed to harmonize epidemiological studies. This homogenization will allow comparing and sharing data collection between European and international studies.\u3c/p\u3

Increased High-Density Lipoprotein Levels Associated with Age-Related Macular Degeneration Evidence from the EYE-RISK and European Eye Epidemiology Consortia

Purpose: Genetic and epidemiologic studies have shown that lipid genes and high-density lipoproteins (HDLs) are implicated in age-related macular degeneration (AMD). We studied circulating lipid levels in relationship to AMD in a large European dataset. Design: Pooled analysis of cross-sectional data. Participants: Individuals (N = 30 953) aged 50 years or older participating in the European Eye Epidemiology (E3) consortium and 1530 individuals from the Rotterdam Study with lipid subfraction data. Methods: AMD features were graded on fundus photographs using the Rotterdam classification. Routine blood lipid measurements, genetics, medication, and potential confounders were extracted from the E3 database. In a subgroup of the Rotterdam Study, lipid subfractions were identified by the Nightingale biomarker platform. Random-intercepts mixed-effects models incorporating confounders and study site as a random effect were used to estimate associations. Main Outcome Measures: AMD features and stage; lipid measurements. Results: HDL was associated with an increased risk of AMD (odds ratio [OR], 1.21 per 1-mmol/l increase; 95% confidence interval [CI], 1.14-1.29), whereas triglycerides were associated with a decreased risk (OR, 0.94 per 1-mmol/l increase; 95% CI, 0.91-0.97). Both were associated with drusen size. Higher HDL raised the odds of larger drusen, whereas higher triglycerides decreases the odds. LDL cholesterol reached statistical significance only in the association with early AMD (P = 0.045). Regarding lipid subfractions, the concentration of extra-large HDL particles showed the most prominent association with AMD (OR, 1.24; 95% CI, 1.10-1.40). The cholesteryl ester transfer protein risk variant (rs17231506) for AMD was in line with increased HDL levels (P = 7.7 x 10(-7)), but lipase C risk variants (rs2043085, rs2070895) were associated in an opposite way (P = 1.0 x 10(-6) and P = 1.6 x 10(-4)). Conclusions: Our study suggested that HDL cholesterol is associated with increased risk of AMD and that triglycerides are negatively associated. Both show the strongest association with early AMD and drusen. Extra-large HDL subfractions seem to be drivers in the relationship with AMD, and variants in lipid genes play a more ambiguous role in this association. Whether systemic lipids directly influence AMD or represent lipid metabolism in the retina remains to be answered. (C) 2018 by the American Academy of Ophthalmolog