Long-term use of everolimus for refractory arrhythmia in a child with tuberous sclerosis complex.

Tuberous sclerosis complex is associated with the occurrence of cardiac rhabdomyomas that may result in life-threatening arrhythmia unresponsive to standard antiarrhythmic therapy. We report the case of an infant with multiple cardiac rhabdomyomas who developed severe refractory supraventricular tachycardia (SVT) that was successfully treated with everolimus. Pharmacological mTOR inhibition rapidly improved arrhythmia within few weeks after treatment initiation and correlated with a reduction in tumor size. Intermediate attempts to discontinue everolimus resulted in rhabdomyoma size rebound and recurrence of arrhythmic episodes, which resolved on resumption of therapy. While everolimus treatment led to successful control of arrhythmia in the first years of life, episodes of SVT reoccurred at the age of 6 years. Electrophysiologic testing confirmed an accessory pathway that was successfully ablated, resulting in freedom of arrhythmic events. In summary we present an in-depth evaluation of the long-term use of everolimus in a child with TSC-associated SVT, including the correlation between drug use and arrhythmia outcome. This case report provides important information on the safety and efficacy of an mTOR inhibitor for the treatment of a potentially life-threatening cardiac disease manifestation in TSC for which the optimal treatment strategy is still not well established.

[The Interdisciplinary Family Consultation in Pediatrics - An Integrative Approach to Complex Burdened Families of Chronically ill Children]. / Die Interdisziplinäre Familienmedizinische Sprechstunde in der Kinderheilkunde ­ Ein integrativer Ansatz für komplex belastete Familien mit einem chronisch kranken Kind.

For families of chronically ill children with a high level of psychosocial stress, it is necessary to involve child and adolescent psychiatric or psychosomatic specialists directly in the pediatric treatment process. For this purpose, a family consultation was set up in the Heidelberg University Pediatrics as part of a model project, which deals with these families in an interdisciplinary and systemic way. It shows that the implementation of the consultation works despite a high organizational effort and is regularly used. The first evaluation results confirm the already described high levels of psychosocial stress in the affected families. They indicate a positive assessment of the consultation and a desire for a permanent offer. First follow-up results indicate a significant decrease in treatment-related concerns, uncertainty and a reduction in treatment-related problems. The lack of a viable funding model poses a challenge for long-term implementation.

Live-virus neutralization of the omicron variant in children and adults 14 months after SARS-CoV-2 wild-type infection.

Data on cross-neutralization of the SARS-CoV-2 omicron variant more than 1 year after SARS-CoV-2 infection are urgently needed, especially in children, to predict the likelihood of reinfection and to guide vaccination strategies. In a prospective observational cohort study, we evaluated live-virus neutralization of the SARS-CoV-2 omicron (BA.1) variant in children compared with adults 14 months after mild or asymptomatic wild-type SARS-CoV-2 infection. We also evaluated immunity to reinfection conferred by previous infection plus COVID-19 mRNA vaccination. We studied 36 adults and 34 children 14 months after acute SARS-CoV-2 infection. While 94% of unvaccinated adults (16/17) and children (32/34) neutralized the delta (B.1.617.2) variant, only 1/17 (5.9%) unvaccinated adults, 0/16 (0%) adolescents and 5/18 (27.8%) children <12 years of age had neutralizing activity against omicron (BA.1). In convalescent adults, one or two doses of mRNA vaccine increased delta and omicron neutralization 32-fold, similar to a third mRNA vaccination in uninfected adults. Neutralization of omicron was 8-fold lower than that of delta in both groups. In conclusion, our data indicate that humoral immunity induced by previous SARS-CoV-2 wild-type infection more than 1 year ago is insufficient to neutralize the current immune escape omicron variant.

Long COVID symptoms in exposed and infected children, adolescents and their parents one year after SARS-CoV-2 infection: A prospective observational cohort study.

BACKGROUND: Long COVID in children and adolescents remains poorly understood due to a lack of well-controlled studies with long-term follow-up. In particular, the impact of the family context on persistent symptoms following SARS-CoV-2 infection remains unknown. We examined long COVID symptoms in a cohort of infected children, adolescents, and adults and their exposed but non-infected household members approximately 1 year after infection and investigated clustering of persistent symptoms within households. METHODS: 1267 members of 341 households (404 children aged <14 years, 140 adolescents aged 14-18 years and 723 adults) were categorized as having had either a SARS-CoV-2 infection or household exposure to SARS-CoV-2 without infection, based on three serological assays and history of laboratory-confirmed infection. Participants completed questionnaires assessing the presence of long COVID symptoms 11-12 months after infection in the household using online questionnaires. FINDINGS: The prevalence of moderate or severe persistent symptoms was statistically significantly higher in infected than in exposed women (36.4% [95% CI: 30.7-42.4%] vs 14.2% [95% CI: 8.7-21.5%]), infected men (22.9% [95% CI: 17.9-28.5%] vs 10.3% [95% CI: 5.8-16.9%]) and infected adolescent girls (32.1% 95% CI: 17.2-50.5%] vs 8.9% [95%CI: 3.1-19.8%]). However, moderate or severe persistent symptoms were not statistically more common in infected adolescent boys aged 14-18 (9.7% [95% CI: 2.8-23.6%] or in infected children <14 years (girls: 4.3% [95% CI: 1.2-11.0%]; boys: 3.7% [95% CI: 1.1-9.6%]) than in their exposed counterparts (adolescent boys: 0.0% [95% CI: 0.0-6.7%]; girls < 14 years: 2.3% [95% CI: 0·7-6·1%]; boys < 14 years: 0.0% [95% CI: 0.0-2.0%]). The number of persistent symptoms reported by individuals was associated with the number of persistent symptoms reported by their household members (IRR=1·11, p=·005, 95% CI [1.03-1.20]). INTERPRETATION: In this controlled, multi-centre study, infected men, women and adolescent girls were at increased risk of negative outcomes 11-12 months after SARS-CoV-2 infection. Amongst non-infected adults, prevalence of negative outcomes was also high. Prolonged symptoms tended to cluster within families, suggesting family-level interventions for long COVID could prove useful. FUNDING: Ministry of Science, Research and the Arts, Baden-Württemberg, Germany.

Missense variant c.1460 T > C (p.L487P) enhances protein degradation of ER mannosyltransferase ALG9 in two new ALG9-CDG patients presenting with West syndrome and review of the literature.

ALG9-CDG is a CDG-I defect within the group of Congenital Disorders of Glycosylation (CDG). We here describe the clinical symptoms of two new and unrelated ALG9-CDG patients, both carrying the novel homozygous missense variant c.1460 T > C (p.L487P) in the ALG9 gene which led to global developmental delay, psychomotor disability, facial dysmorphisms, brain and heart defects, hearing loss, hypotonia, as well as feeding problems. New clinical symptoms comprised West syndrome with hypsarrhythmia. Quantitative RT-PCR analysis revealed a significantly enhanced ALG9 mRNA transcript level, whereas the protein amount in fibroblasts was significantly reduced. This could be ascribed to a stronger degradation of the mutated ALG9 protein in patient fibroblasts. Lipid-linked oligosaccharide analysis showed an ALG9-CDG characteristic accumulation of Man6GlcNAc2-PP-dolichol and Man8GlcNAc2-PP-dolichol in patient cells. The clinical findings of our patients and of all previously published ALG9-CDG patients are brought together to further expand the knowledge about this rare N-glycosylation disorder. SYNOPSIS: Homozygosity for p.L487P in ALG9 causes protein degradation and leads to West syndrome.

The calcium-sensing receptor stabilizes podocyte function in proteinuric humans and mice.

Calcimimetic agents allosterically increase the calcium ion sensitivity of the calcium-sensing receptor (CaSR), which is expressed in the tubular system and to a lesser extent in podocytes. Activation of this receptor can reduce glomerular proteinuria and structural damage in proteinuric animal models. However, the precise role of the podocyte CaSR remains unclear. Here, a CaSR knockdown in cultured murine podocytes and a podocyte-specific CaSR knockout in BALB/c mice were generated to study its role in proteinuria and kidney function. Podocyte CaSR knockdown abolished the calcimimetic R-568 mediated calcium ion-influx, disrupted the actin cytoskeleton, and reduced cellular attachment and migration velocity. Adriamycin-induced proteinuria enhanced glomerular CaSR expression in wild-type mice. Albuminuria, podocyte foot process effacement, podocyte loss and glomerular sclerosis were significantly more pronounced in adriamycin-treated podocyte-specific CaSR knockout mice compared to wild-type littermates. Co-treatment of wild-type mice with adriamycin and the calcimimetic cinacalcet reduced proteinuria in wild-type, but not in podocyte-specific CaSR knockout mice. Additionally, four children with nephrotic syndrome, whose parents objected to glucocorticoid therapy, were treated with cinacalcet for one to 33 days. Proteinuria declined transiently by up to 96%, serum albumin increased, and edema resolved. Thus, activation of podocyte CaSR regulates key podocyte functions in vitro and reduced toxin-induced proteinuria and glomerular damage in mice. Hence, our findings suggest a potential novel role of CaSR signaling in control of glomerular disease.

Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 in Households with Children, Southwest Germany, May-August 2020.

Resolving the role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in households with members from different generations is crucial for containing the current pandemic. We conducted a large-scale, multicenter, cross-sectional seroepidemiologic household transmission study in southwest Germany during May 11-August 1, 2020. We included 1,625 study participants from 405 households that each had ≥1 child and 1 reverse transcription PCR-confirmed SARS-CoV-2-infected index case-patient. The overall secondary attack rate was 31.6% and was significantly higher in exposed adults (37.5%) than in children (24.6%-29.2%; p = <0.015); the rate was also significantly higher when the index case-patient was >60 years of age (72.9%; p = 0.039). Other risk factors for infectiousness of the index case-patient were SARS-CoV-2-seropositivity (odds ratio [OR] 27.8, 95% CI 8.26-93.5), fever (OR 1.93, 95% CI 1.14-3.31), and cough (OR 2.07, 95% CI 1.21-3.53). Secondary infections in household contacts generate a substantial disease burden.

Transient elastography correlated to four different histological fibrosis scores in children with liver disease.

Currently, liver histology is the gold standard for the detection of liver fibrosis. In recent years, new methods such as transient elastography (TE) have been introduced into clinical practice, which allow a non-invasive assessment of liver fibrosis. The aim of the present study was to investigate the predictive value of TE for higher grade fibrosis and whether there is any relevance which histologic score is used for matching. For this purpose, we compared TE with 4 different histologic scores in pediatric patients with hepatopathies. Furthermore, we also determined the aspartate aminotransferase-to-platelet ratio (APRI) score, another non-invasive method, to investigate whether it is equally informative. Therefore, liver fibrosis in 75 children was evaluated by liver biopsy, TE and laboratory values. Liver biopsies were evaluated using four common histological scoring systems (Desmet, Metavir, Ishak and Chevalier's semi-quantitative scoring system). The median age of the patients was 12.3 years. TE showed a good correlation to the degree of fibrosis severity independent of the histological scoring system used. The accuracy of the TE to distinguish between no/minimal fibrosis and severe fibrosis/cirrhosis was good (p = 0.001, AUC-ROCs > 0.81). The optimal cut-off value for the prediction of severe fibrosis was 10.6 kPa. In contrast, the APRI score in our collective showed no correlation to fibrosis.Conclusion: TE shows a good correlation to the histological findings in children with hepatopathy, independent of the used histological scoring system. What is Known: • The current gold standard for detecting liver fibrosis is liver biopsy. Novel non-invasive ultrasound-based methods are introduced to clinical diagnostics. • Most histological scores have been developed and evaluated in adult populations and for only one specific liver disease. What is New: • Transient elastography (TE) in children showed a good correlation to fibrosis severity irrespective of the utilized histological scoring system. • The aspartate aminotransferase-to-platelet ratio (APRI) showed no correlation with different stages of liver fibrosis in children.

Prevalence of SARS-CoV-2 Infection in Children and Their Parents in Southwest Germany.

Importance: School and daycare closures were enforced as measures to confine the novel coronavirus disease 2019 (COVID-19) pandemic, based on the assumption that young children may play a key role in severe acute respiratory coronavirus 2 (SARS-CoV-2) spread. Given the grave consequences of contact restrictions for children, a better understanding of their contribution to the COVID-19 pandemic is of great importance. Objective: To describe the rate of SARS-CoV-2 infections and the seroprevalence of SARS-CoV-2 antibodies in children aged 1 to 10 years, compared with a corresponding parent of each child, in a population-based sample. Design, Setting, and Participants: This large-scale, multicenter, cross-sectional investigation (the COVID-19 BaWü study) enrolled children aged 1 to 10 years and a corresponding parent between April 22 and May 15, 2020, in southwest Germany. Exposures: Potential exposure to SARS-CoV-2. Main Outcomes and Measures: The main outcomes were infection and seroprevalence of SARS-CoV-2. Participants were tested for SARS-CoV-2 RNA from nasopharyngeal swabs by reverse transcription-polymerase chain reaction and SARS-CoV-2 specific IgG antibodies in serum by enzyme-linked immunosorbent assays and immunofluorescence tests. Discordant results were clarified by electrochemiluminescence immunoassays, a second enzyme-linked immunosorbent assay, or an in-house Luminex-based assay. Results: This study included 4964 participants: 2482 children (median age, 6 [range, 1-10] years; 1265 boys [51.0%]) and 2482 parents (median age, 40 [range, 23-66] years; 615 men [24.8%]). Two participants (0.04%) tested positive for SARS-CoV-2 RNA. The estimated SARS-CoV-2 seroprevalence was low in parents (1.8% [95% CI, 1.2-2.4%]) and 3-fold lower in children (0.6% [95% CI, 0.3-1.0%]). Among 56 families with at least 1 child or parent with seropositivity, the combination of a parent with seropositivity and a corresponding child with seronegativity was 4.3 (95% CI, 1.19-15.52) times higher than the combination of a parent who was seronegative and a corresponding child with seropositivity. We observed virus-neutralizing activity for 66 of 70 IgG-positive serum samples (94.3%). Conclusions and Relevance: In this cross-sectional study, the spread of SARS-CoV-2 infection during a period of lockdown in southwest Germany was particularly low in children aged 1 to 10 years. Accordingly, it is unlikely that children have boosted the pandemic. This SARS-CoV-2 prevalence study, which appears to be the largest focusing on children, is instructive for how ad hoc mass testing provides the basis for rational political decision-making in a pandemic.

Optimized Trientine-dihydrochloride Therapy in Pediatric Patients With Wilson Disease: Is Weight-based Dosing Justified?

OBJECTIVES: The aim of the study was to investigate the efficacy and safety of trientine-dihydrochloride (TD) in pediatric patients with Wilson disease (WD) and the effect of different weight-based dosages on their clinical and biochemical outcome. METHODS: We retrospectively reviewed the clinical data of 31 children with WD receiving TD therapy ages under 18 years at the time of diagnosis. Outcome measures included parameters of copper metabolism and liver function tests. To examine the impact of different weight-based dosages, 2 dosage subgroups were analyzed. Group 1 received less than 20 mg/kg TD per day, group 2 more than 20 mg ·â€Škg-1 ·â€Šday-1. RESULTS: Median follow-up was 60 (5-60) months in the total study group. During TD therapy, nonceruloplasmin-bound copper was reduced from mean 1.53 (0.01-6.95) at baseline to 0.62 (0.01-4.57) µmol/l. 24h-urinary copper excretion diminished to 1.85 (0.8-9.6) µmol/day approximating the therapeutic goal of 1.6 µmol/day. Seven of 31 patients (22.6%) required discontinuation of TD treatment, in 4 cases it was because of adverse events (ulcerative colitis, gingival and breast hypertrophy, hirsutism, elevation of transaminases).Investigations about weight-based dosage showed no significant difference of any laboratory parameter between the 2 cohorts. But in terms of clinical safety, adverse effects because of TD were only found in 6.7% of children in group 1 (<20 mg ·â€Škg-1 ·â€Šday-1, median follow-up 60 [9-60] months), whereas in group 2 (>20 mg ·â€Škg-1 ·â€Šday-1, median follow-up 60 [14-60] months), it was 63.6%. CONCLUSIONS: TD proves to be an efficacious alternative chelating agent for children with WD. Weight-based dosages above the recommended 20 mg ·â€Škg-1 ·â€Šday-1 may increase the rate of adverse effects in pediatric patients.

The Phenotypic Spectrum of PRRT2-Associated Paroxysmal Neurologic Disorders in Childhood.

Pathogenic variants in PRRT2, encoding the proline-rich transmembrane protein 2, have been associated with an evolving spectrum of paroxysmal neurologic disorders. Based on a cohort of children with PRRT2-related infantile epilepsy, this study aimed at delineating the broad clinical spectrum of PRRT2-associated phenotypes in these children and their relatives. Only a few recent larger cohort studies are on record and findings from single reports were not confirmed so far. We collected detailed genetic and phenotypic data of 40 previously unreported patients from 36 families. All patients had benign infantile epilepsy and harbored pathogenic variants in PRRT2 (core cohort). Clinical data of 62 family members were included, comprising a cohort of 102 individuals (extended cohort) with PRRT2-associated neurological disease. Additional phenotypes in the cohort of patients with benign sporadic and familial infantile epilepsy consist of movement disorders with paroxysmal kinesigenic dyskinesia in six patients, infantile-onset movement disorders in 2 of 40 individuals, and episodic ataxia after mild head trauma in one girl with bi-allelic variants in PRRT2. The same girl displayed a focal cortical dysplasia upon brain imaging. Familial hemiplegic migraine and migraine with aura were reported in nine families. A single individual developed epilepsy with continuous spikes and waves during sleep. In addition to known variants, we report the novel variant c.843G>T, p.(Trp281Cys) that co-segregated with benign infantile epilepsy and migraine in one family. Our study highlights the variability of clinical presentations of patients harboring pathogenic PRRT2 variants and expands the associated phenotypic spectrum.

Axenfeld-Rieger Anomaly and Neuropsychiatric Problems-More than Meets the Eye.

OBJECTIVE: The main purpose of this article is to demonstrate the co-occurrence of Axenfeld-Rieger anomaly and neuropsychiatric problems as clinical signs of genetically determined cerebral small vessel disease in two patients. CASE STUDY: We report on two adolescent individuals with ocular anterior segment dysgenesis (Axenfeld-Rieger anomaly) presenting with neuropsychiatric symptoms. Both patients underwent cerebral magnetic resonance imaging showing white matter T2-hyperintensities involving different brain regions, suspective of cerebral small vessel disease. Genetic analysis revealed pathogenic mutations in the FOXC1 gene (patient 1) and the COL4A1 gene (patient 2), respectively. CONCLUSION: We report on the co-occurrence of ocular anterior segment dysgenesis (Axenfeld-Rieger anomaly) and neuropsychiatric symptoms as clinical signs of genetically determined cerebral small vessel disease in two patients. In both patients, the cerebral lesions involved the frontotemporal regions, brain regions that control social behavior as well as executive and cognitive function, highlighting the fact that neuropsychiatric symptoms may be early clinical presentations of cerebral small vessel disease. We further provide a review of monogenic causes of pediatric cerebral small vessel disease, emphasizing the links to childhood-onset neuropsychiatric disease.

[Gene therapies for neuromuscular diseases]. / Gentherapien für neuromuskuläre Erkrankungen.

BACKGROUND: For a long time the treatment of neuromuscular diseases was considered to be purely symptomatic. Due to new technologies in recent years novel causal forms of treatment could be developed. Gene therapies for spinal muscular atrophy, Duchenne muscular dystrophy, limb-girdle muscular dystrophy, myotubular myopathy and hereditary motor and sensory neuropathy type 1A are currently being evaluated in clinical trials. Initial preliminary results are promising and the first preparation onasemnogene abeparvovec-xioi (Zolgensma®) for the treatment of spinal muscular atrophy has recently been approved by the U.S. Food and Drug Administration (FDA). OBJECTIVE: This review describes the principles of gene therapy, summarizes the interim results published so far and provides an overview of currently active or soon to be initiated gene therapy trials. CONCLUSION: Gene therapies have the potential to significantly influence the course of neuromuscular diseases. First positive intermediate results have been published and the first treatment has recently been approved in the USA. Long-term data on sustained effects and toxicity of gene therapies are not yet available. These novel treatment options will present new challenges for the healthcare systems concerning diagnosis, treatment and reimbursement.

Pediatric in-hospital emergencies: real life experiences, previous training and the need for training among physicians and nurses.

OBJECTIVE: Pediatric emergencies challenge professional teams by demanding substantial cognitive effort, skills and effective teamwork. Educational designs for team trainings must be aligned to the needs of participants in order to increase effectiveness. To assess these needs, a survey among physicians and nurses of a tertiary pediatric center in Germany was conducted, focusing on previous experience, previous training in emergency care, and individual training needs. RESULTS: Fifty-three physicians and 75 nurses participated. Most frequently experienced emergencies were respiratory failure, resuscitation, seizure, shock/sepsis and arrhythmia. Resuscitations were perceived as being particularly precarious. Team collaboration and communication were major issues arising from previous emergency situations, but perceptions differed between physicians and nurses. Regarding previous training, physicians were accustomed to self-directed learning, whereas nurses usually attended practical courses. Both physicians and nurses rated themselves as having moderate levels of knowledge and skills for pediatric emergencies, though residents reported the significantly lowest preparedness. Both professions reported a high need for training of basic procedures and emergency algorithms, physicians even more than nurses.

Bioenergetic dysfunction in a zebrafish model of acute hyperammonemic decompensation.

Acute hyperammonemic encephalopathy is a life-threatening manifestation of individuals with urea cycle disorders, which is associated with high mortality rates and severe neurological sequelae in survivors. Cerebral bioenergetic failure has been proposed as one of the key mechanisms underlying hyperammonemia-induced brain damage, but data supporting this hypothesis remain inconclusive and partially contradictory. Using a previously established zebrafish model of acute hyperammonemic decompensation, we unraveled that acute hyperammonemia leads to a transamination-dependent withdrawal of 2-oxoglutarate (alpha-ketoglutarate) from the tricarboxylic acid (TCA) cycle with consecutive TCA cycle dysfunction, ultimately causing impaired oxidative phosphorylation with ATP shortage, decreased ATP/ADP-ratio and elevated lactate concentrations. Thus, our study supports and extends the hypothesis that cerebral bioenergetic dysfunction is an important pathophysiological hallmark of hyperammonemia-induced neurotoxicity.

Pharmacologic rescue of hyperammonemia-induced toxicity in zebrafish by inhibition of ornithine aminotransferase.

Hyperammonemia is the common biochemical hallmark of urea cycle disorders, activating neurotoxic pathways. If untreated, affected individuals have a high risk of irreversible brain damage and mortality. Here we show that acute hyperammonemia strongly enhances transamination-dependent formation of osmolytic glutamine and excitatory glutamate, thereby inducing neurotoxicity and death in ammoniotelic zebrafish larvae via synergistically acting overactivation of NMDA receptors and bioenergetic impairment induced by depletion of 2-oxoglutarate. Intriguingly, specific and irreversible inhibition of ornithine aminotransferase (OAT) by 5-fluoromethylornithine rescues zebrafish from lethal concentrations of ammonium acetate and corrects hyperammonemia-induced biochemical alterations. Thus, OAT inhibition is a promising and effective therapeutic approach for preventing neurotoxicity and mortality in acute hyperammonemia.

Point shear wave elastography (pSWE) using Acoustic Radiation Force Impulse (ARFI) imaging: a feasibility study and norm values for renal parenchymal stiffness in healthy children and adolescents.

AIMS: To evaluate the applicability of point shear wave elastography (pSWE) for measuring renal parenchymal stiffness in healthy children and adolescents and to establish norm values for shear wave speed (SWS) using two ARFI methods and ultrasound probes. MATERIAL AND METHODS: We prospectively investigated 264 children (43.9% males). pSWE (Virtual TouchTM Quantification and Virtual TouchTM Imaging Quantification (VTQ and VTIQ; Siemens, Germany)) was performed in the renal cortex of 528 healthy kidneys using a 1-6 MHz convex and a 4-9 MHz linear ultrasound probe in ventrolateral and dorsal examinations. Feasibility and reproducibility of pSWE measurements were evaluated. SWS values were analysed with regard to age, body dimensions, kidney volume and measuring depth. RESULTS: pSWE measurements were successful in >95% of subjects using the low and in <60% using the high-frequency probe. Mean SWS values (m/s) differed by method and probe: 2.10±0.43 (VTQ1-6MHz, convex, ventrolateral), 2.30±0.37 (VTQ1-6MHz, convex, dorsal), 1.58±0.44 (VTQ4-9MHz, linear, dorsal) and 1.96±0.27 (VTIQ4-9MHz, linear, dorsal). SWS was positively correlated with age, weight and body height, but independent of sex, BMI, or kidney volume and depth. CONCLUSIONS: pSWE (VTQ) is a feasible method to evaluate renal parenchymal stiffness in children of all ages. SWS values are age and weight dependent and differ significantly between high- and low-frequency probes. High-frequency probes and VTIQ should only be used in children <10 years.

Improving Pediatric Basic Life Support Performance Through Blended Learning With Web-Based Virtual Patients: Randomized Controlled Trial.

BACKGROUND: E-learning and blended learning approaches gain more and more popularity in emergency medicine curricula. So far, little data is available on the impact of such approaches on procedural learning and skill acquisition and their comparison with traditional approaches. OBJECTIVE: This study investigated the impact of a blended learning approach, including Web-based virtual patients (VPs) and standard pediatric basic life support (PBLS) training, on procedural knowledge, objective performance, and self-assessment. METHODS: A total of 57 medical students were randomly assigned to an intervention group (n=30) and a control group (n=27). Both groups received paper handouts in preparation of simulation-based PBLS training. The intervention group additionally completed two Web-based VPs with embedded video clips. Measurements were taken at randomization (t0), after the preparation period (t1), and after hands-on training (t2). Clinical decision-making skills and procedural knowledge were assessed at t0 and t1. PBLS performance was scored regarding adherence to the correct algorithm, conformance to temporal demands, and the quality of procedural steps at t1 and t2. Participants' self-assessments were recorded in all three measurements. RESULTS: Procedural knowledge of the intervention group was significantly superior to that of the control group at t1. At t2, the intervention group showed significantly better adherence to the algorithm and temporal demands, and better procedural quality of PBLS in objective measures than did the control group. These aspects differed between the groups even at t1 (after VPs, prior to practical training). Self-assessments differed significantly only at t1 in favor of the intervention group. CONCLUSIONS: Training with VPs combined with hands-on training improves PBLS performance as judged by objective measures.

Dopamine-Responsive Growth-Hormone Deficiency and Central Hypothyroidism in Sepiapterin Reductase Deficiency.

Sepiapterin reductase (SR) deficiency is a rare autosomal recessively inherited error of tetrahydrobiopterin (BH4) biosynthesis, resulting in disturbed dopaminergic and serotonergic neurotransmission. The clinical phenotype is characterized by dopa-responsive movement disorders including muscular hypotonia, dystonia, and parkinsonism. Due to the rarity of the disease, the phenotype of SR deficiency is far from being completely understood. Here, we report a 7-year-old boy, who was referred for diagnostic evaluation of combined psychomotor retardation, spastic tetraplegia, extrapyramidal symptoms, and short stature. Due to discrepancy between motor status and mental condition, analyses of biogenic amines and pterins in CSF were performed, leading to the diagnosis of SR deficiency. The diagnosis was confirmed by a novel homozygous mutation c.530G>C; p.(Arg177Pro) in exon 2 of the SPR gene. Because of persistent short stature, systematic endocrinological investigations were initiated. Insufficient growth-hormone release in a severe hypoglycemic episode after overnight fasting confirmed growth-hormone deficiency as a cause of short stature. In addition, central hypothyroidism was present. A general hypothalamic affection could be excluded. Since dopamine is known to regulate growth-hormone excretion, IGF-1, IGF-BP3, and peripheral thyroid hormone levels were monitored under L-dopa/carbidopa supplementation. Both growth-hormone-dependent factors and thyroid function normalized under treatment. This is the first report describing growth-hormone deficiency and central hypothyroidism in SR deficiency. It extends the phenotypic spectrum of the disease and identifies dopamine depletion as cause for the endocrinological disturbances.