Population-based screening in children for early diagnosis and treatment of familial hypercholesterolemia: design of the VRONI study.

BACKGROUND: Heterozygous familial hypercholesterolemia (FH) represents the most frequent monogenic disorder with an estimated prevalence of 1:250 in the general population. Diagnosis during childhood enables early initiation of preventive measures, reducing the risk of severe consecutive atherosclerotic manifestations. Nevertheless, population-based screening programs for FH are scarce. METHODS: In the VRONI study, children aged 5-14 years in Bavaria are invited to participate in an FH screening program during regular pediatric visits. The screening is based on low-density lipoprotein cholesterol measurements from capillary blood. If exceeding 130 mg/dl (3.34 mmol/l), i.e. the expected 95th percentile in this age group, subsequent molecular genetic analysis for FH is performed. Children with FH pathogenic variants enter a registry and are treated by specialized pediatricians. Furthermore, qualified training centers offer FH-focused training courses to affected families. For first-degree relatives, reverse cascade screening is recommended to identify and treat affected family members. RESULTS: Implementation of VRONI required intensive prearrangements for addressing ethical, educational, data safety, legal and organizational aspects, which will be outlined in this article. Recruitment started in early 2021, within the first months, more than 380 pediatricians screened over 5200 children. Approximately 50 000 children are expected to be enrolled in the VRONI study until 2024. CONCLUSIONS: VRONI aims to test the feasibility of a population-based screening for FH in children in Bavaria, intending to set the stage for a nationwide FH screening infrastructure. Furthermore, we aim to validate genetic variants of unclear significance, detect novel causative mutations and contribute to polygenic risk indices (DRKS00022140; August 2020).

Population-based screening in children for early diagnosis and treatment of familial hypercholesterolemia: design of the VRONI study.

Familial hypercholesterolemia (FH) is the most frequent monogenic disorder (prevalence 1:250) in the general population. Early diagnosis during childhood enables pre-emptive treatment, thus reducing the risk of severe atherosclerotic manifestations later in life. Nonetheless, FH screening programs are scarce. VRONI offers all children aged 5-14 years in Bavaria a FH screening in the context of regular pediatric visits. LDL-cholesterol (LDL-C) is measured centrally, followed by genetic analysis for FH if exceeding the age-specific 95th percentile (130 mg/dl, 3.34 mmol/l). Children with FH pathogenic variants are treated by specialized pediatricians and offered a FH-focused training course by a qualified training center. Reverse cascade screening is recommended for all first-degree relatives. VRONI aims to prove the feasibility of a population-based FH screening in children and to lay the foundation for a nationwide screening program.

[Banks, archives or libraries? Models for the ethical foundation of biobanks]. / Bank, Archiv oder Bibliothek? ­ Denkmodelle für das ethische Fundament von Biobanken.

At present, when it comes to research with biomedical data, research interests and data protection seem to be irreconcilable. Such differences are best mediated by an institution. The presuppositions of biobanking can be productively questioned with respect to public libraries. These represent a successful combination of knowledge and power, security and freedom.

Sacred hearts and pumps: cardiology and the conflicted body politic (1500-1900).

This article examines how conflicting notions of the body politic between the natural and the spiritual have contextualised the evolution of cardiology. After a brief look at the place of the heart in biblical, patristic and medieval notions of the church, the article turns to the Reformation period. While Martin Luther moved theological gravity to the individual's heart and conscience, his contemporary Michael Servetus described the pulmonary cycle in the context of an antitrinitarian theology condemned as theological and political heresy. In the early modern period, nature conceived as creation grounded sovereign political authority, which science could then align with. Whereas William Harvey still adhered to an Aristotelian teleology, René Descartes and subsequent mechanistic contributions to cardiology were flanked by an intense 'cardiolatry'. Both, it is argued, are two sides of the same, almost non-corporeal coin. The emerging Enlightened epistemology allowed for a position distinct from both sovereign and ecclesial powers. The French Revolution was a paradigm shift: the ancien régime falls, and its Sacred Heart devotion is mocked; the new 'Erastian' state-university emerges as the context of cardiology. These developments are reflected in the life of René Laënnec and in cultural interpretations of the heart later in the 19th century. It is shown that the heart as a doubly inscribed, both biological and spiritual organ, played a central role in theological, and therefore political and scientific notions of the body politic. These continue to haunt the present, allowing us to interpret normative appeals to the heart particularly in political contexts.

Personalised Medicine: The Promise, the Hype and the Pitfalls.

In engaging critically with personalised medicine and mapping pitfalls which mark its progress this project aims to stimulate conversations which deal intelligently with controversies for the sake of consensus. We aim to ask the ethical questions which will lead to the improvement of healthcare and we take an open-minded approach to finding answers to them over time. What is or should be meant by 'personalised medicine' is a major theme of this issue. It is a debate bound up with question of both values in the sense of ethical reflection and value in the sense of economic return. This editorial discusses and interrelates the articles of the issue under four headings: the promise and the hype of personalised medicine; the human person and the communication of risk; data sharing and participation; value, equity and power. A key intention throughout is to provoke discourse and debate, to identify aspirations which are more grounded in myth or hype than reality and to challenge them; and to identify focussed, practical questions which need further examination.