SNP array profiling of childhood adrenocortical tumors reveals distinct pathways of tumorigenesis and highlights candidate driver genes

Childhood adrenocortical tumors (ACT) are rare malignancies, except in southern Brazil, where a higher incidence rate is associated to a high frequency of the founder R337H TP53 mutation. To date, copy number alterations in these tumors have only been analyzed by low-resolution comparative genomic hybridization.

Adolescent survivors of childhood cancer: are they vulnerable for psychological distress?

OBJECTIVES: We aimed to (i) evaluate psychological distress in adolescent survivors of childhood cancer and compare them to siblings and a norm population; (ii) compare the severity of distress of distressed survivors and siblings with that of psychotherapy patients; and (iii) determine risk factors for psychological distress in survivors. METHODS: We sent a questionnaire to all childhood cancer survivors aged <16 years when diagnosed, who had survived ≥5 years and were aged 16-19 years at the time of study. Our control groups were same-aged siblings, a norm population, and psychotherapy patients. Psychological distress was measured with the Brief Symptom Inventory-18 (BSI-18) assessing somatization, depression, anxiety, and a global severity index (GSI). Participants with a T-score ≥57 were defined as distressed. We used logistic regression to determine risk factors. RESULTS: We evaluated the BSI-18 in 407 survivors and 102 siblings. Fifty-two survivors (13%) and 11 siblings (11%) had scores above the distress threshold (T ≥ 57). Distressed survivors scored significantly higher in somatization (p = 0.027) and GSI (p = 0.016) than distressed siblings, and also scored higher in somatization (p ≤ 0.001) and anxiety (p = 0.002) than psychotherapy patients. In the multivariable regression, psychological distress was associated with female sex, self-reported late effects, and low perceived parental support. CONCLUSIONS: The majority of survivors did not report psychological distress. However, the severity of distress of distressed survivors exceeded that of distressed siblings and psychotherapy patients. Systematic psychological follow-up can help to identify survivors at risk and support them during the challenging period of adolescence. Copyright © 2013 John Wiley & Sons, Ltd.

Farming environments and childhood atopy, wheeze, lung function, and exhaled nitric oxide

Previous studies have demonstrated that children raised on farms are protected from asthma and allergies. It is unknown whether the farming effect is solely mediated by atopy or also affects nonatopic wheeze phenotypes.

Rhinovirus infections in infancy and early childhood

Rhinovirus (RV) infections occur early and recurrently in life, imposing a significant burden of disease on infants and young children. They are the most frequent causative agents of both upper and lower respiratory tract infections in this age group and are associated with a broad variety of clinical outcomes, ranging from asymptomatic infections to severe respiratory disease requiring hospitalisation. In addition to their impact on short-term morbidity, RVs are also debated as important pathogens in the development of recurrent wheeze and/or asthma. Several studies in infants at high-risk for atopy and asthma and in hospitalised children have demonstrated that recurrent wheezing illnesses induced by RVs early in life are a risk factor for the development of asthma later in childhood. However, underlying mechanisms are poorly understood. The question whether RVs are directly involved in the development of childhood wheeze and asthma, or whether symptomatic RV infections only represent a proxy for infants prone to develop obstructive lung diseases, is still open. In this review we provide an overview on the role of RVs as important disease-causing agents from infancy to early childhood and discuss their contribution to the subsequent development of childhood wheeze and/or asthma.

[Arterial-ischaemic stroke in childhood]

The risk to have a stroke during childhood is at least as frequent as to suffer from a brain tumour. Unlike adults, in whom ischaemic strokes overweigh haemorrhagic strokes, ischaemic and haemorrhagic strokes are equally frequent in children, occurring with an incidence of 2 - 3/100'000 children/year. Even though the clinical presentation of arterial-ischaemic stroke in children (pedAIS) is similar to adults, time to diagnosis is longer. The delay to diagnosis is mainly explained by the low index of suspicion of both the general population and the medical personnel, a broad range of differential diagnoses, and the fact that diagnostic imaging in children often requires sedation, which is not always readily available. PedAIS is a multiple risk problem, usually occurring due to a combination of risk factors, such as infectious diseases, dehydration, trauma or an underlying condition such as congenital heart disease. Still little is known about the appropriate management of pedAIS. Supportive measures are considered to be the mainstay of therapy. The use of antithrombotic medication depends on pedAIS aetiology. In an ongoing multicenter trial, the safety and effectiveness of thrombolysis are currently being investigated. PedAIS carries an important mortality and morbidity, with neurological and neuropsychological deficits persisting in two thirds of the affected children.

[Childhood's determinants for high blood pressure in adulthood]

Hypertension has been estimated to affect 20 - 25% of the adult population and represents an important risk factor for cardiovascular disease like coronary heart disease, stroke and peripheral artery occlusive disease. In addition, hypertension supports the development and progression of chronic kidney insufficiency. The interaction of multiple genetic and environmental factors are felt to influence the level of blood pressure. Epidemiological data in the sixties and seventies demonstrated a correlation between cardiovascular disease and infant mortality in the same population. In the late eighties Barker and coworkers described a strong correlation between low birth weight and increased risk for the development of cardiovascular complications. It has been supposed that factors influencing the intrauterine growth and development can lead to adult cardiovascular diseases, known as the concept of "fetal programming". Beside the effect of fetal programming, multiple (preventable and non-preventable) factors determine the blood pressure level in childhood, which will define adult blood pressure level through the blood pressure tracking from childhood to adulthood. Hence, the prevention of cardiovascular disease in adulthood begins in childhood through identification of preventable risk factors as for example obesity and passive smoking and recognition of risk groups like small for gestational age or preterm children.