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摘要： The aim of this study was to disentangle mechanisms of epileptogenesis in monogenic epilepsies in children. We reviewed paediatric monogenic epilepsies excluding brain malformation or an inborn error of metabolism, but including the gene function whether there is loss-of-function or gain-of-function, age at gene expression when available, and associated epilepsy syndrome. Genes for which at least five patients with similar epilepsy phenotype had been reported were selected. Three mechanisms are shared by most monogenic epilepsies: (1) excess of N-methyl-d-aspartate (NMDA) transmission activation (NMDA-pathies);(2) abnormal gamma-aminobutyric acid (GABA) transmission with reduced inhibition (phasic GABA-pathies);and (3) tonic activation of extrasynaptic GABA(A) receptors by extracellular GABA (tonic GABA-pathies). NMDA-pathies comprise early epileptic encephalopathy with suppression-burst, neonatal/infantile benign seizures, West and Lennox-Gastaut syndromes, and encephalopathy with continuous spike waves in slow sleep, thus brief seizures with major interictal spiking. Phasic GABA-pathies comprise mostly generalized epilepsy with febrile seizures plus and Dravet syndrome, thus long-lasting seizures with mild interictal spiking. Tonic GABA-pathies cause epilepsy with myoclonic-atonic seizures and Angelman syndrome, thus major high-amplitude slow-wave activity. This pathophysiological approach to monogenic epilepsies provides diagnostic clues and helps to guide treatment strategy. What this paper adds In paediatric monogenic epilepsies, electroclinical patterns point to three main mechanisms: NMDA-pathies, and phasic and tonic GABA-pathies. Antiepileptic treatment choice could be guided by each of these mechanisms.

摘要： Every year, approximately 2500 children are referred for developmental or behavioural concerns to outpatient clinics at the Centre for Community Child Health (CCCH), Royal Children's Hospital (RCH), Melbourne. Of 2718 referrals received, 405 were rejected; 134 were excluded because the child was re-referred and seen at RCH, the referral was for the Sleep Clinic (as its intake criteria differ to other CCCH clinics) or contact details were incorrect. 4 GP, general practitioner; RCH, Royal Children's Hospital; SD, standard deviation; SEIFA, socio-economic indexes for areas. [Extracted from the article]

关键词： Children   Computed tomography angiography   Congenital heart disease   Heart   Heterotaxy   Isomerism  

摘要： BackgroundHeterotaxy refers to the abnormal arrangement of organs across the left-right axis and is typically associated with complex cardiovascular *** characterise the range of cardiac and extracardiac CT angiography findings in children with heterotaxy using the latest nomenclature consensus and to compare the different types of *** and methodsWe retrospectively analysed the data of 64 consecutive paediatric patients referred to our tertiary paediatric cardiovascular centre who underwent CT angiography for the evaluation of known or suspected heterotaxy within a 52-month *** atrial isomerism was identified in 44 (69%) children, while left atrial isomerism was identified in 18 (28%) children. Atrial appendage anatomy and situs could not be determined in 2 children (3%). Associated heart defects included complete atrioventricular canal (CAVC) in 51 (80%) children, total anomalous pulmonary venous return in 43 (67%) and pulmonary atresia in 23 (36%). The bronchial branching pattern corresponded to atrial appendage morphology in all children except in the two in whom atrial appendage morphology could not be defined. In children with right atrial isomerism, the most common associated abnormalities were CAVC (n=41, 93%) and asplenia (n=34, 77%), while in those with left atrial isomerism, the most common associated abnormalities were polysplenia (n=17, 94%) and an interrupted inferior vena cava with azygos continuation (n=15, 83%).ConclusionCT angiography provides useful cardiovascular and extracardiac data on heterotaxy, which frequently involves a pattern of side-related findings but has great anatomical variability.

关键词： Eating disorders   Perfectionism   Anxiety   Depression   Children   HOPE Project   Adolescents  

摘要： Objective: The aim was to examine in children and adolescents with eating disorders the relationship between perfectionism, anxiety, and depression at intake assessment and whether intake perfectionism was significantly associated with anxiety and depression at 6 months and 12 months post-intake review. Method: Participants were 167 females aged 10-17 years (M = 14.6, SD = 1.20) with a diagnosis of an eating disorder, who were assessed at intake to an eating disorders treatment program to receive either inpatient, day or outpatient care. Participants were re-assessed at 6 and 12 months post-intake review. Results: At intake and 6 and 12 months post intake review perfectionism had a significant positive correlation with anxiety and depression. Perfectionism did not however determine change in anxiety and depression over time at 6 and 12 months post-intake review. Conclusions: Despite perfectionism being significantly associated with anxiety and depression, further research is required to explore the relationships between perfectionism, anxiety and depression over time.

关键词： Research quality   Bias   Pediatric epilepsy surgery   Cognitive  

摘要： Purpose: RCTs are the gold standard in determining intervention efficacy with journal impact factor assumed to index research quality. Flint et al's (2017) systematic review examined neurocognitive outcomes following paediatric temporal lobe epilepsy surgery. Retrieved evidence was restricted to non-RCTs, which pose greater risk of bias and thus diminish research quality. The current study evaluated risk of bias in sources retrieved by Flint et al. and explored whether impact factor related to research quality within this selected field. Methods: Methodological and reporting bias was evaluated using categories of bias specified by Cochrane. The relationship between the identified number of biases and journal impact factors of retrieved sources was examined. Results: All studies carried substantial risk for bias. Methodology bias included low sample size (76.71%;56/73), risk of confounding cognitive outcomes due to failure to report pre-surgery neurocognitive data (21.92%;16/73) and to determine whether patients were prescribed antiepileptic drugs at follow-up (53.42%;39/73). Reporting bias included overstating claims based on findings (53.42%;39/73), failure to report individual patient characteristics (66%;33/50) and omitting the nature of surgical interventions (15.07%;11/73). The number of sources of common bias within studies was not associated significantly with journal impact factor (p = .878). Conclusion: This evaluation highlights risk of bias when sources are predominantly uncontrolled non-RCTs and provides evidence that journal impact factor is not a reliable indicator of quality within this field. Authors should limit bias in their methods and reporting of results, to ensure the highest quality evidence possible is used to inform treatment decisions and prognosis.

摘要： Acute lymphoblastic leukaemia (ALL) is the most common childhood cancer. Therapies for paediatric ALL have improved such that more than 80% of patients survive to 5 years post-therapy, and most survive to adulthood. However, these ALL patients experience long-term side effects, which permanently affect their quality of life. Bone loss is the most common skeletal abnormality in paediatric ALL survivors, and 40% of patients experience a fracture before therapy completion. Reduced longitudinal growth (short stature) is another significant side effect of ALL therapy. The drugs dexamethasone (DEX), doxorubicin (DOX), vincristine (VIN) and L-asparaginase are used to treat paediatric ALL patients. Juvenile (4-week old) mice were treated with the individual chemotherapy agents (a single dose of DOX, and up to 2 weeks of injections of the other drugs) in addition to combination therapy of all drugs (CTx). The effects of these chemotherapy agents on longitudinal growth and bone parameters were investigated at 12-weeks of age. MicroCT revealed that DOX and CTx significantly decreased the longitudinal growth of the mice. DOX and CTx also caused significant reductions in trabecular bone volume (TBV), trabecular thickness and trabecular number (TN). VIN significantly decreased TBV and TN. The trabecular separation was significantly increased by DOX, DEX, VIN and CTx. The mean cortical thickness, area, endocortical perimeter, and mean polar moment of inertia were also significantly decreased by DOX and CTx. The bone phenotypes observed in the mice treated with DOX or CTx are consistent with increased fracture risks. In conclusion, a single injection of DOX in juvenile mice was sufficient to cause the majority of the bone phenotypes that are commonly observed in paediatric ALL patients. Furthermore, CTx had a more profound effect on these bone phenotypes than DOX alone.

摘要： The article presents a case study of a 1-year-old boy who developed a catheter related bacteraemia infection after a subclavian CVC was inserted for home parenteral nutrition post a emergency bowel surgery. Topics discussed include the catheter having provided a niche for the Dermacoccus bacteria strain to enter the infant's bloodstream.

关键词： bullying   child abuse   craniocerebral trauma   paediatric emergency medicine   violence  

摘要： Objective Although there is a large body of research on head injury (HI) inflicted by caregivers in young children, little is known about intentional HI in older children and inflicted HI by perpetrators other than carers. Therefore, we set out to describe epidemiology, demographics and severity of intentional HIs in childhood. Methods A planned secondary analysis of a prospective multicentre cohort study was conducted in 10 EDs in Australia and New Zealand, including children aged <18 years with HIs. Epidemiology codes were used to prospectively code the injuries. Demographic and clinical information including the rate of clinically important traumatic brain injury (ciTBI: HI leading to death, neurosurgery, intubation >1 day or admission >= 2 days with abnormal computed tomography [CT]) was descriptively analysed. Results Intentional injuries were identified in 372 of 20 137 (1.8%) head-injured children. Injuries were caused by caregivers (103, 27.7%), by peers (97, 26.1%), by siblings (47, 12.6%), by strangers (35, 9.4%), by persons with unknown relation to the patient (21, 5.6%), other intentional injuries (8, 2.2%) or undetermined intent (61, 16.4%). About 75.7% of victims of assault by caregivers were <2 years, whereas in other categories, only 4.9% were <2 years. Overall, 66.9% of victims were male. Rates of CT performance and abnormal CT varied: assault by caregivers 68.9%/47.6%, by peers 18.6%/27.8%, by strangers 37.1%/5.7%. ciTBI rate was 22.3% in assault by caregivers, 3.1% when caused by peers and 0.0% with other perpetrators. Conclusions Intentional HI is infrequent in children. The most frequently identified perpetrators are caregivers and peers. Caregiver injuries are particularly severe.

关键词： anesthesia   children   equipment and supplies   equipment safety   general   pediatrics   spoton thermometry   temperature   thermometry   validation  

摘要： Background Maintenance of thermal homeostasis is of crucial importance in the anesthetized pediatric patient. Gold-standard methods for central core temperature measurement are however inappropriately invasive and impractical in daily practice. The SpotOn sensor uses zero-heat-flux thermometry technology and claims to bypass the invasiveness of classical methods and still accurately display central core temperatures. Up to date no formal analysis of this method in children has taken place. Aims The primary objective was to assess the accuracy in comparison with esophageal temperature;the secondary objective concerned the safety of the SpotOn sensor in the pediatric patients. Methods Fifty-four children aged 1-12 years with an American Society of Anesthesiology classification I or II scheduled to undergo elective surgical procedures under general anesthesia for a minimum of 30 minutes were included. Exclusion criteria included: fragile forehead skin, procedures impeding proper SpotOn placement, thoracoscopic or gastroesophageal procedures, coagulopathy, hemodynamic instability, or vasoactive medication use. After sevoflurane induction, an esophageal temperature probe was placed in the lower third of the esophagus, and a SpotOn sensor on the lateral forehead. Temperatures were recorded in pairs per 1 minute intervals. Temperatures were subjected to bias analysis with 0.5 degrees C as the a priori established clinical significance cutoff. Results Bland-Altman analysis revealed the two methods differed on average 0.14 degrees C (95% limits of agreement: -0.39 to 0.66), with 89.5% of the differences being under 0.5 degrees C. No significant differences could be found between the two methods for the established 0.5 degrees C cutoff. Linear regression analysis determined the following linear regression equation: 0.837x + 5.86 (R-2 = 0.738). Lin's concordance correlation coefficient of 0.83 (95% CI: 0.81-0.84). No complications were observed with the use of the SpotOn senso

关键词： Cancer models   Cancer therapy   CNS cancer   Paediatric cancer   Tumour immunology  

摘要： The spectrum of tumours arising in childhood is fundamentally different from that seen in adults, and they are known to be divergent from adult malignancies in terms of cellular origins, epidemiology, genetic complexity, driver mutations and underlying mutational processes. Despite the immense knowledge generated through sequencing efforts and functional characterization of identified (epi-) genetic alterations over the past decade, the clinical implications of this knowledge have so far been limited. Novel preclinical platforms such as the European Innovative Therapies for Children with Cancer-Paediatric Preclinical Proof-of-Concept Platform and the US-based Pediatric Preclinical Testing Consortium are being developed to try to change this by aiming to recapitulate the extensive heterogeneity of paediatric tumours and thereby, hopefully, improve the ability to predict clinical benefit. Numerous studies have also been established worldwide to provide patients with access to real-time molecular profiling and the possibility of more precise mechanism-of-action-based treatments. In addition to tumour-intrinsic findings and mechanisms, ongoing studies are investigating features such as the immune microenvironment of paediatric tumours in comparison with adult cancers - currently of very timely clinical relevance. However, there is an ongoing need for rigorous preclinical biomarker and target validation to feed into the next generation of molecularly stratified clinical trials. This Review aims to provide a comprehensive state-of-the-art overview of the molecular landscape of paediatric solid tumours, including their underlying genomic alterations and interactions with the microenvironment, complemented with our current understanding of potential therapeutic vulnerabilities and how these can be preclinically tested using more accurate predictive methods. Finally, we provide an outlook on the challenges and opportunities associated with translating this overwhelming scien