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Background: Data suggest that metabolites, other than blood phenylalanine (Phe), better and independently predict clinical outcomes in patients with phenylketonuria (PKU). Methods: To find new biomarkers, we compared the results of untargeted lipidomics and metabolomics in treated adult PKU patients to those of matched controls. Samples (lipidomics in EDTA-plasma (22 PKU and 22 controls) and metabolomics in serum (35 PKU and 20 controls)) were analyzed using ultra-high-performance liquid chromatography and high-resolution mass spectrometry. Data were subjected to multivariate (PCA, OPLS-DA) and univariate (Mann–Whitney U test, p < 0.05) analyses. Results: Levels of 33 (of 20,443) lipid features and 56 (of 5885) metabolite features differed statistically between PKU patients and controls. For lipidomics, findings include higher glycerolipids, glycerophospholipids, and sphingolipids species. Significantly lower values were found for sterols and glycerophospholipids species. Seven features had unknown identities. Total triglyceride content was higher. Higher Phe and Phe catabolites, tryptophan derivatives, pantothenic acid, and dipeptides were observed for metabolomics. Ornithine levels were lower. Twenty-six metabolite features were not annotated. Conclusions: This study provides insight into the metabolic phenotype of PKU patients. Additional studies are required to establish whether the observed changes result from PKU itself, diet, and/or an unknown reason. [ABSTRACT FROM AUTHOR]

AbstractIn the Netherlands, rates of euthanasia and physician-assisted suicide (henceforth “EPAS”) display substantial variation at the municipal level. If a similar variation can be found in non-assisted suicide (henceforth “suicide”), this may enable us to establish a possible correlation between these variations. This cross-sectional study assessed proportions of suicide in the years 2013–2017 in The Netherlands. Negative binomial regression analysis was performed to identify potential explanatory variables and to calculate adjusted proportions. The magnitude of variation was calculated by ratios between the highest and lowest municipality proportions. Outliers were detected by Funnel Plots. A possible correlation between suicide and EPAS was calculated. From 2013–2017 the suicide rate between Dutch municipalities varied by a factor 6.7. This variation could only be partially explained by gender, political orientation, the availability of voluntary workers, and mobility limitations. No correlation was found with the variation in EPAS. A “waterbed effect” between suicides and EPAS-cases could not be confirmed. Advice for further research is given. [ABSTRACT FROM AUTHOR]

The case description regards a nine-years old patient who, as a consequence of a very serious epilepsy syndrome, several forms of comorbidity, severe developmental impairments, and the absence of meaningful contact with relatives, is felt to be in very serious suffering. Parents and physicians decide to end the child's life by withholding nutrition and hydration. Based on this case description and on the parents' experiences, its authors argue in favour of a stately regulated procedure for active life termination. In this comment I argue that the regulation of life termination without a patient request should remain a no-go area. If we allow life termination in children, there is no reason why we should not also allow such requests on behalf of incompetent patients such as handicapped adults and elderly patients with advanced dementia who have not issued an advance directive. Let the very rare cases in which a doctor sees no other option than to terminate an infant's life, remain in the realm of the non-regulated.