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关键词： Telomeres   Alternative lengthening of telomeres   H3   3   Paediatric high-grade gliomas   pHGG  

摘要： Purpose The maintenance of telomere length prevents cancer cell senescence and occurs via two mutually exclusive mechanisms: (a) reactivation of telomerase expression and (b) activation of alternative lengthening of telomeres (ALT). ALT is frequently related to alterations on ATRX, a chromatin-remodelling protein. Recent data have identified different molecular subgroups of paediatric high-grade glioma (pHGG) with mutations of H3F3A, TERTp and ATRX;however, differences in telomere length among these molecular subgroups were not thoroughly examined. Methods We investigated which genetic alterations trigger the ALT mechanism in 52 IDH-wildtype, 1p/19q-wildtype pHGG. Samples were analysed for telomere length using Tel-FISH. ATRX nuclear loss of expression was assessed by IHC, H3F3A and TERTp mutations by DNA sequencing, and TERTp methylation by MS-PCR. Results Mutant H3.3 was found in 21 cases (40.3%): 19.2% with K27M mutation and 21.1% with G34R mutation. All H3.3G34R-mutated cases showed the ALT phenotype (100%);on the opposite, only 40% of the H3.3K27M-mutated showed ALT activation. ATRX nuclear loss was seen in 16 cases (30.7%), associated sometimes with the G34R mutation, and never with the K27M mutation. ATRX nuclear loss was always related to telomere elongation. TERTp C250T mutations were rare (5.4%) and were not associated with high intensity Tel-FISH signals, as TERTp hyper-methylation detected in 21% of the cases. H3.3/ATRX/TERTp-wildtype pHGG revealed all basal levels of telomere length. Conclusion Our results show a strong association between H3.3 mutations and ALT, and highlight the different telomeric profiles in histone-defined subgroups: H3.3-G34R mutants always trigger ALT to maintain telomere length, irrespective of ATRX status, whereas only some H3.3-K27M tumours activate ALT. These findings suggest that acquiring the gly34 mutation on H3.3 might suffice to trigger the ALT mechanism.

关键词： F-18 FDG   Bone marrow   Hodgkin lymphoma   PET/CT  

摘要： Objectives: The present study aimed to investigate the diagnostic performance of F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in the detection of bone marrow involvement (BMI) in paediatric Hodgkin lymphoma (HL) through a systematic review and meta-analysis. Methods: PubMed, Cochrane, and EMBASE databases were searched from the earliest available date of indexing till March 31, 2020 for studies evaluating the diagnostic performance of F-18 FDG PET/CT in the detection of BMI in paediatric HL. Results: Across seven studies (1265 patients), the pooled sensitivity of F-18 FDG PET or PET/CT was 0.95 (95% confidence interval [CI]: 0.87-0.98) with heterogeneity (I-2 = 86.2, p < 0.001), and the pooled specificity was 0.97 (95% CI: 0.84-1.00) with heterogeneity (I-2 = 97.2, p < 0.001). Likelihood ratio syntheses provided an overall positive likelihood ratio of 37.8 (95% CI: 5.2-274.9) and a negative likelihood ratio of 0.05 (95% CI: 0.02-0.14). The pooled diagnostic odds ratio was 732 (95% CI: 55-9806). The area under the summary receiver operating characteristic curve was 0.98 (95% CI: 0.97-0.99). Conclusions: The present meta-analysis revealed high sensitivity and specificity of F-18 FDG PET/CT for the detection of BMI in paediatric HL. Currently, the literature regarding the use of F-18 FDG PET/CT for the detection of BMI in paediatric HL is limited. Large multicentre studies are necessary to substantiate the diagnostic accuracy of F-18 FDG PET/CT in the detection of BMI in paediatric HL. Advances in knowledge: Through a meta-analysis, this study provided a more reliable assessment of the diagnostic utility of F-18 FDG PET/CT, which exhibited good diagnostic accuracy in the detection of BMI in paediatric HL.

关键词： follow‐   up care   healthcare provider   multidisciplinary   paediatric brain tumour   qualitative   survivorship  

摘要： Objective Paediatric brain tumour (PBT) survivors face high risks of disabling long-term and late effects. Whether survivors' needs are met in a system with publicly funded services, but in the absence of a formal long-term follow-up model, is uncertain. Empirically based recommendations for a national model are needed. We explored multidisciplinary healthcare providers' (HCP) experiences with providing such care. Methods We conducted five focus-group interviews and five individual interviews with a nationally representative sample of 33 Norwegian HCPs. Focus-group interviews and individual interviews were analysed using systematic text condensation. Results Three main themes were identified: (a) 'Providing care above and beyond system constraints', describing a perceived discrepancy between HCPs' knowledge of, and their ability to meet, the survivors' needs. (b) 'System barriers to providing optimal follow-up care', describing a perceived lack of routines for communication and coordination between the HCPs and existing care services. (c) 'Nurses and shared-care to improve care', including empowering nurses and establishing routines for collaborations and areas of responsibilities. Conclusion The current healthcare system was perceived not to fully meet the survivors' needs. Nurse-led care models, including standardised patient-care pathways, were suggested to increase the accessibility of already-existing services and thus to improve long-term follow-up care.

关键词： catheter ablation   paediatric cardiology   paediatric psychology   self-report   tachyarrhythmia  

摘要： Aim: Assess executive and socio-emotional/behavioural functioning in paediatric supraventricular tachycardia (SVT) patients. Methods: SVT patients aged 7-17 who had not undergone catheter ablation were included. Parents completed the Child Behaviour Checklist (CBCL/6-18) and the Behavior Rating Inventory of Executive Functioning (BRIEF). Participants age 11-17 years completed the Youth Self-Report (YSR/11-18) and the BRIEF Self-Report (BRIEF-SR). One-sample z test was used to compare questionnaire results to the average t-score range (M = 50, SD = 10). Results: Thirty (18 female) children/adolescents participated (M = 12.6 years old, SD = 3.2 years) with a mean SVT onset age of 7 years (SD = 4.3 years). BRIEF and BRIEF-SR results suggested no difference in executive functioning f rom average. Mean t-scores of CBCL/6-18 and YSR/11-18 subscales Anxious/Depressed, Withdrawn/ Depressed, Somatic Complaints, Thought Problems, Diagnostic and Statistical Manual of Mental Disorders (DSM) Affective Problems, DSM Anxiety Problems and DSM Somatic Problems were significantly elevated compared to average. YSR/11-18 subscales Social Problems, Attention Problems, Internalizing Problems, DSM ADHD Problems and DSM Oppositional Defiant Problems had elevated mean t-scores compared to average. Effect sizes were small to medium (0.2 <= d <= 0.8). Conclusion: Paediatric patients with SVT potentially have a greater risk of developing behaviour, especially internalizing, problems compared to similarly aged children/ adolescents without SVT.

关键词： changes   children   costs   evidence‐   based medicine   surgery   trends  

摘要： Objectives Tonsillectomy and adenoidectomy in children are controversial subjects with large regional variation in surgical rates, partly explained by cultural differences and lack of high-quality evidence on indications for surgery. A quality of care cycle was executed on this topic in the Netherlands. The objective of this study was to estimate changes in healthcare utilisation for paediatric tonsil surgery in the Netherlands. Methods Population-based data on tonsillectomies and adenoidectomies in children up to age 10 were retrieved retrospectively from Dutch administrative databases between 2005 and 2018. A change point analysis was performed to detect the most pivotal change point in surgical rates. We performed univariate analyses to compare surgical patients' characteristics before and after the pivotalpoint . Impact on healthcare budget and societal costs were estimated using current prices and data from cost-effectiveness analyses. Results The annual number of adenotonsillectomies reduced by 10 952 procedures (-39%;from 129 per 10 000 children to 87 per 10 000 children) between 2005 and 2018, and the number of adenoidectomies by 14 757 procedures (-49%;from 138 per 10 000 children to 78 per 10 000 children). The most pivotal change point was observed around 2012, accompanied by small changes in patient selection for surgery before and after 2012. An estimated euro5.3 million per year was saved on the healthcare budget and euro10.4 million per year on societal costs. Conclusion The quality of care cycle resulted in fewer operations, with a concomitant reduction of costs. We suggest that part of these savings be invested in new research to maintain the quality of care cycle.

关键词： bacteraemia   Escherichia coli   outcome   risk factor   urinary tract infection  

摘要： Aim: Escherichia coli (E coli) is a known cause of paediatric bacteraemia. The main objective was to characterise the emergency department (ED) presentations of paediatric E coli bacteraemia and secondarily to identify those related to greater severity. Methods: This was a sub-study of a multicentre cross-sectional prospective registry including all with E coli bacteraemia episodes between 2011 and 2016. We used multiple correspondence and cluster analysis to identify different patterns. Results: We included 291 patients and 43 met criteria for severe disease (14.3%, 95% confidence interval 11.2-19.3). We identified four types of paediatric E coli bacteraemia presentations. Two (178 patients, 61.2%) were related to well-appearing previously healthy infants with associated urinary tract infection (UTI). Well-appearing children older than 12 months old with underlying disease (n = 60, 20.6%) and non-well-appearing children of different ages (n = 53, 18.2%) corresponded to the other two types;these had associated UTI infrequently and higher severity rate (15% and 50.9%, respectively, higher when compared with the two previous types, P < .01), including the two patients who died. Conclusion: There were four different types of ED paediatric E coli bacteraemia presentations with different severity. Febrile young children with associated UTI showed the best outcome.

摘要： Point-of-care ultrasound (POCUS) is a growing interesting tool in the emergency setting. Its usefulness in diagnostic and therapeutic pathway of patients with respiratory distress in addition to clinical evaluation is well established in adult emergency medicine while paediatric specific data, although growing, remain limited. We report a case series of paediatric patients presenting with respiratory distress successfully diagnosed with cardiac dysfunction following POCUS evaluations. Lung POCUS, in combination with cardiac POCUS, is a very useful supplementary diagnostic tool to assess the breathless child and to rapidly identify life-threatening primary etiologies or secondary physiologies. Thus, fast echocardiography is a desirable aid for paediatric emergency physicians and should be supported in all paediatric emergency settings following an adequate training that is mandatory regarding image acquisition and data interpretation.

关键词： COVID-19   MIS-C   multisystem inflammatory syndrome   PIMS-TS   SARS-CoV-2  

摘要： The novel post SARS-COV2 Paediatric Inflammatory Syndrome, first recognized in April 2020, took worldwide clinicians by surprise. There rapidly followed a plethora of case definitions, nomenclatures, descriptive papers, and guidelines on treatment. There has been controversy around this condition. Is it really new? Is it an atypical form of a known disease? How should we communicate and report such cases? What is the pathogenesis? Which treatments are given, and which are effective? What are the short and long-term outcomes? We are all learning fast. The clinical and immunological patterns seen are unique. There are significant differences in both presentation and pathogenesis to any known condition, including Kawasaki's disease. This implies that treatments are not necessarily transferrable: and indeed it is unknown which treatments are effective at all. Outcomes, as far as are known, are good, but long term data is lacking. The international cooperation has been an example of how today's connected medicine can be a force for good, however calm assessment of evidence remains necessary to ensure the best outcomes for our patients. This short article identifies what we have learnt from the first surge of COVID-19 cases about paediatric inflammatory syndrome and how it affects children. © 2020

关键词： Fragility index   Fragility quotient   Meta-analysis   Uninformative statistic   P value  

摘要： Purpose Meta-analyses occupy the highest level of evidence and thereby guide clinical decision-making. Recently, randomised-controlled trials were evaluated for the robustness of their findings by calculating the fragility index. The fragility index is the number of events that needs to be added to one treatment arm until the statistical significance collapses. We, therefore, aimed to evaluate the robustness of paediatric surgical meta-analyses. Methods We searched MEDLINE for paediatric surgical meta-analyses in the last decade. All meta-analyses on a paediatric surgical condition were eligible for analysis if they based their conclusion on a statistically significant meta-analysis. Results We screened 303 records and conducted a full-text evaluation of 60 manuscripts. Of them, 39 were included in our analysis that conducted 79 individual meta-analyses with significant results. Median fragility index was 5 (Q25-Q75% 2-11). Median fragility in relation to included patients was 0.77% (Q25-Q75% 0.29-1.87%). Conclusion Paediatric surgical meta-analyses are often fragile. In almost 60% of results, the statistical significance depends on less than 1% of the included population. However, as the fragility index is just a transformation of the P value, it basically conveys the same information in a different format. It therefore should be avoided.