Cees Noordam

Background: Adolescent obesity remains a challenge with limited treatment options. GLP-1 receptor agonists such as liraglutide (Saxenda^®) have shown efficacy in trials, but real-world data in youth are scarce. Methods: This retrospective longitudinal, non-interventional study analyzed 22 adolescents treated with liraglutide in a Swiss pediatric endocrinology center. All received non-structured nutritional/lifestyle counseling with three-monthly follow-up. BMI standard deviation scores (BMI-SDS) and adverse effects were recorded. Results: The mean age at initiation was 14.9 years (range 12.5–17.5); 15 patients had Southern European immigrant background. Mean treatment duration was 8.2 months (range 1–18). BMI-SDS decreased significantly from +2.63 (IQR +2.4/+2.8) to +2.40 (IQR +2.2/+2.6). Median intra-individual reduction was −0.20 (IQR −0.28/−0.10), p = 0.0003 with large effect size (rb = −0.77). Thirteen patients discontinued treatment, mainly due to insufficient weight loss or mild nausea. In the patients continuing therapy BMI-SDS decreased from +2.59 (IQR +2.4/+2.8) to +2.08 (IQR +1.9/+2.4). No serious adverse events occurred. Conclusions: Liraglutide showed a comparable efficacy to the pivotal clinical trial in reducing BMI-SDS in adolescents, while the side-effect profile was similarly mild and consistent with previously reported data. Discontinuation rates remained high, highlighting the need for thorough pre-treatment counseling on expected mild, transient symptoms and strategies to mitigate nausea. Future prospective studies are needed to assess long-term outcomes and identify patient characteristics associated with greater treatment success, to better individualize GLP-1–based therapy in adolescent obesity.

Background/Objectives: The 2019 Swiss growth references for height, weight, and BMI were based on a large dataset from the German-speaking part of Switzerland (Cohort 2019). The current study aimed to ensure national representativeness by proportionate amounts of additional data from the French-speaking (Suisse Romande) and Italian-speaking (Ticino) regions to validate the 2019 growth curves and to update the national growth references. It also investigated the influence of parental migration background on child growth. Methods: Anthropometric data from 43,290 children and adolescents—including 11,816 new cases—were analyzed (Cohort 2019 + 2025). Percentile curves were modeled using the Generalized Additive Models for Location, Scale, and Shape (GAMLSS) framework. Results: The extended dataset largely confirms the 2019 growth references. Variations in height percentiles were small and clinically negligible. Clinically relevant differences in BMI percentiles were observed in girls, with the most pronounced deviations—up to 0.8 kg/m²—at the 97th percentile. Analyses by parental migration background revealed relevant differences in BMI. Conclusions: The extended Swiss Growth References (Cohort 2019 + 2025) are robust and provide valid reference data for all Swiss children and adolescents, offering contemporary tools for decision-making in clinical practice. To maintain their validity over time, targeted updates are required, with special attention to demographic changes resulting from migration.

Noonan syndrome is a heterogeneous congenital disorder. The main features are typical facial features, short stature and cardiac defects. The diagnosis is clinical: in 80% of patients with Noonan syndrome a genetic defect can be shown. Inheritance is predominantly autosomal dominant and seldom autosomal recessive. In 2001, PTPN11 was the first gene connected to Noonan syndrome, and until now, at least 20 other genes have been discovered. All genes code for proteins involved in the RAS-MAP-kinase pathway, and therefore, Noonan syndrome is one of the known RASopathies. Other RASopathies include neurofibromatosis and CFC syndrome. Short stature is one of the defining features of Noonan syndrome. The cause is not fully understood but is multifactorial. Other endocrinological features are confined to delayed puberty and hypogonadism in boys and males. To increase adult height, children with Noonan syndrome have been treated with human growth hormone since the 1990s. This seems to be beneficial in most of the children treated. In this narrative review, we describe the current knowledge on growth, endocrinological features and growth hormone treatment in patients with Noonan syndrome.

Prader-Labhart-Willi syndrome (PWS) is a rare genetic disorder characterized by intellectual disability, behavioural problems, hypothalamic dysfunction and specific dysmorphisms. Hypothalamic dysfunction causes dysregulation of energy balance and endocrine deficiencies, including hypogonadism. Although hypogonadism is prevalent in males and females with PWS, knowledge about this condition is limited. In this review, we outline the current knowledge on the clinical, biochemical, genetic and histological features of hypogonadism in PWS and its treatment. This was based on current literature and the proceedings and outcomes of the International PWS annual conference held in November 2019. We also present our expert opinion regarding the diagnosis, treatment, care and counselling of children and adults with PWS-associated hypogonadism. Finally, we highlight additional areas of interest related to this topic and make recommendations for future studies.

Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: Being separated from home and relatives is a major stressor for children and adolescents when hospitalized. Children long for a manner to be distracted, pleasured, and socially connected during hospitalization. Different technological devices have been applied in health care to answer those needs. Both virtual reality (VR) and videoconferencing have proven their value in hospital wards and pediatrics. VisitU combines these 2 technologies innovatively. VisitU is a recently launched VR product enabling users to be virtually at home during hospitalization. Objective: This study aims to explore the experiences of hospitalized patients with the VR intervention of VisitU in addition to standard care. Methods: Over a 3-month period, a purposive sample of 10 patients hospitalized in the Radboudumc Amalia Children’s Hospital was included in this qualitative study. Semistructured interviews were performed, one before and one after the use of the VR device. Patients were asked open-ended questions concerning their experiences with VisitU on practical, cognitive, emotional, and social domains. The interviews were audiorecorded and transcribed verbatim. Atlas.ti was used to support the qualitative analysis. Furthermore, the inductive thematic analysis was done according to the 6-step procedure described by Braun and Clarke. Results: Over a 3-month period, a purposive sample of 10 patients hospitalized in the Radboudumc Amalia Children’s Hospital was included in this qualitative study. Semistructured interviews were performed, one before and one after the use of the VR device. Patients were asked open-ended questions concerning their experiences with VisitU on practical, cognitive, emotional, and social domains. The interviews were audiorecorded and transcribed verbatim. Atlas.ti was used to support the qualitative analysis. Furthermore, the inductive thematic analysis was done according to the 6-step procedure described by Braun and Clarke. Conclusions: This study shows the positive experiences of pediatric patients with VR live streaming. VisitU brings together the needs of patients and possibilities of VR and videoconferencing; it offers patients a way out of the hospital. Nevertheless, practical and technical obstacles must be overcome and side effects are an area of further research.

The aim of this retrospective study is to describe ocular findings in a large Noonan syndrome cohort and to detect associations between ocular features and genetic mutations that were not found in earlier studies. We collected ophthalmological and genetic data of 105 patients (median age, 12 years; range, 0–60 years) clinically diagnosed as Noonan syndrome. The ocular findings were linked to the genotypes. All patients with Noonan syndrome showed multiple abnormalities in the categories of vision and refraction, external ocular features, ocular alignment and motility, anterior ocular segment, and posterior ocular segment. In total, 50 patients have NS due to a mutation in PTPN11. Permanent visual impairment (bilateral best-corrected visual acuity < 0.3) was found in 7 patients, including patients with a mutation in RAF1, SHOC2, and KRAS. Keratoconus was found in 2 PTPN11 positive patients, and prominent corneal nerves were observed in a patient with a SOS1 mutation. Conclusions: This study shows an overview of ocular abnormalities in Noonan syndrome, including permanent visual impairment caused by binocular optic nerve abnormalities and nystagmus. Delay in ophthalmological diagnosis is still present, also in patients with visual impairment. All Noonan syndrome patients should have a complete ophthalmological examination at the time of diagnosis. What is Known: • Although we discover more pathogenic mutations in patients with Noonan syndrome, Noonan syndrome still is a clinical diagnosis • Ocular features of Noonan syndrome are characterized by developmental anomalies of the eyelids and associated with other ocular abnormalities in childhood (including refractive errors, strabismus and amblyopia). What is New: • There seems to be a delay in the ophthalmological diagnosis and awareness of the broad variety ofophthalmological features including refractive errors and visual impairment in Noonan syndrome is needed. All children should have a full ophthalmological examination at the time of diagnosis. • Permanent visual impairment (best-corrected visual acuity < 0.3) is found in patients with mutations in RAF1, SHOC2, and KRAS and the cause is probably a developmental disorder of the optic nerves.

BACKGROUND Being separated from home and relatives is a major stressor for children and adolescents when hospitalized. Children long for a manner to be distracted, pleasured, and socially connected during hospitalization. Different technological devices have been applied in health care to answer those needs. Both virtual reality (VR) and videoconferencing have proven their value in hospital wards and pediatrics. VisitU combines these 2 technologies innovatively. VisitU is a recently launched VR product enabling users to be virtually at home during hospitalization. OBJECTIVE This study aims to explore the experiences of hospitalized patients with the VR intervention of VisitU in addition to standard care. METHODS Over a 3-month period, a purposive sample of 10 patients hospitalized in the Radboudumc Amalia Children’s Hospital was included in this qualitative study. Semistructured interviews were performed, one before and one after the use of the VR device. Patients were asked open-ended questions concerning their experiences with VisitU on practical, cognitive, emotional, and social domains. The interviews were audiorecorded and transcribed verbatim. Atlas.ti was used to support the qualitative analysis. Furthermore, the inductive thematic analysis was done according to the 6-step procedure described by Braun and Clarke. RESULTS The following 6 main themes were the result of the qualitative analysis: “Being hospitalized,” “Expectations of VisitU,” “VisitU in use,” “VisitU, the benefits,” “The impact of VisitU,” and “Barriers when using VisitU.” The way VisitU was used by patients varied. The main benefits of VisitU were being somewhere else, being at home, and facilitating social connection. Limitations were experienced on the technical abilities, physical side effects, and complexity of use. Despite that, patients were positive about VisitU and unanimous in the view that they would like to use it again and advise other patients to use it. CONCLUSIONS This study shows the positive experiences of pediatric patients with VR live streaming. VisitU brings together the needs of patients and possibilities of VR and videoconferencing; it offers patients a way out of the hospital. Nevertheless, practical and technical obstacles must be overcome and side effects are an area of further research.

Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet

Although problems with motor performance in daily life are frequently mentioned in Noonan syndrome, the motor performance profile has never been systematically investigated. The aim of this study was to examine whether a specific profile in motor performance in children with Noonan syndrome was seen using valid norm‐referenced tests. The study assessed motor performance in 19 children with Noonan syndrome (12 females, mean age 9 years 4 months, range 6 years 1 month to 11 years and 11 months, SDS 1 year and 11 months). More than 60% of the parents of the children reported pain, decreased muscle strength, reduced endurance, and/or clumsiness in daily functioning. The mean standard scores on the Visual Motor Integration (VMI) test and Movement Assessment Battery for Children 2, Dutch version (MABC‐2‐NL) items differed significantly from the reference scores. Grip strength, muscle force, and 6 min Walking Test (6 MWT) walking distance were significantly lower, and the presence of generalized hypermobility was significantly higher. All MABC‐2‐NL scores (except manual dexterity) correlated significantly with almost all muscle strength tests, VMI total score, and VMI visual perception score. The 6 MWT was only significantly correlated to grip strength. This is the first study that confirms that motor performance, strength, and endurance are significantly impaired in children with Noonan syndrome. Decreased functional motor performance seems to be related to decreased visual perception and reduced muscle strength. Research on causal relationships and the effectiveness of interventions is needed. Physical and/or occupational therapy guidance should be considered to enhance participation in daily life.