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Nicolaides–Baraitser syndrome is a rare, neuro-developmental disorder caused by heterozygous pathogenic variants in the SMARCA2 gene, involved with chromatin regulation. Cardinal features include intellectual disability, short stature, microcephaly, triangular facies, sparse hair, brachydactyly, prominent interphalangeal joints and seizures. Genetic testing demonstrated a loss within SMARCA2 at 9p24.3 inclusive of basepairs 2094861_2141830 (hg19) in our patient. This case highlights a child with Nicolaides–Baraiter syndrome, a SMARCA2 gene deletion and a novel association of hypertrophic obstructive cardiomyopathy.

We present the case of a 4 year-old boy post heart transplantation who presented with signs and symptoms of critical airway obstruction and was initially diagnosed with infective supraglottitis. Following re-presentation and biopsy, this was confirmed as post-transplant lymphoproliferative disorder (PTLD) in an unusual site; laryngeal PTLD is rare. The patient failed standard therapy and ultimately was successfully treated with EBV-specific cytotoxic T lymphocytes (CTL). This case describes a rare presentation of PTLD which required a novel treatment approach including elective tracheostomy prior to CTL therapy. The treatment was successful and the patient was decannulated prior to discharge following 4 negative biopsies, the most recent 6 months following treatment completion. The case also highlights the importance of extra-vigilance in the post-transplant population and of a collaborative approach between multiple specialties across two separate countries including the transplant center and the referral center.

Childhood hypertrophic cardiomyopathy; Outcomes; Phenotype Miocardiopatía hipertrófica infantil; Resultados; Fenotipo Miocardiopatia hipertròfica infantil; Resultats; Fenotip Background Up to one-half of childhood sarcomeric hypertrophic cardiomyopathy (HCM) presents before the age of 12 years, but this patient group has not been systematically characterized. Objectives The aim of this study was to describe the clinical presentation and natural history of patients presenting with nonsyndromic HCM before the age of 12 years. Methods Data from the International Paediatric Hypertrophic Cardiomyopathy Consortium on 639 children diagnosed with HCM younger than 12 years were collected and compared with those from 568 children diagnosed between 12 and 16 years. Results At baseline, 339 patients (53.6%) had family histories of HCM, 132 (20.9%) had heart failure symptoms, and 250 (39.2%) were prescribed cardiac medications. The median maximal left ventricular wall thickness z-score was 8.7 (IQR: 5.3-14.4), and 145 patients (27.2%) had left ventricular outflow tract obstruction. Over a median follow-up period of 5.6 years (IQR: 2.3-10.0 years), 42 patients (6.6%) died, 21 (3.3%) underwent cardiac transplantation, and 69 (10.8%) had life-threatening arrhythmic events. Compared with those presenting after 12 years, a higher proportion of younger patients underwent myectomy (10.5% vs 7.2%; P = 0.045), but fewer received primary prevention implantable cardioverter-defibrillators (18.9% vs 30.1%; P = 0.041). The incidence of mortality or life-threatening arrhythmic events did not differ, but events occurred at a younger age. Conclusions Early-onset childhood HCM is associated with a comparable symptom burden and cardiac phenotype as in patients presenting later in childhood. Long-term outcomes including mortality did not differ by age of presentation, but patients presenting at younger than 12 years experienced adverse events at younger ages. This work was supported by the British Heart Foundation (grant FS/16/72/32270) to Drs Norrish and Kaski. This work is (partly) funded by the National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre. Dr Norrish is supported by Great Ormond Street Hospital Children’s Charity. Drs Field and Kaski are supported by Max’s Foundation and Great Ormond Street Hospital Children’s Charity. Dr Kaski is supported by a Medical Research Council–National Institute for Health Research Clinical Academic Research Partnership award. This work was financially supported by the Foundation for Paediatric Research of Finland (Dr Ojala). Dr Fernandez has received speaker fees from Sanofi-Genzyme. Dr Kubus is supported by MH CZ – DRO, Motol University Hospital (00064203). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Increasingly the importance of how and why we make decisions in the medical arena has been questioned. Traditionally the aeronautical and business worlds have shed a light on this complex area of human decision-making. In this review we reflect on what we already know about the complexity of decision-making in addition to directing particular focus on the challenges to decision-making in the high-intensity environment of the pediatric cardiac catheterization laboratory. We propose that the most critical factor in outcomes for children in the catheterization lab may not be technical failures but rather human factors and the lack of preparation and robust shared decision-making process between the catheterization team. Key technical factors involved in the decision-making process include understanding the anatomy, the indications and objective to be achieved, equipment availability, procedural flow, having a back-up plan and post-procedural care plan. Increased awareness, pre-catheterization planning, use of standardized clinical assessment and management plans and artificial intelligence may provide solutions to pitfalls in decision-making. Further research and efforts should be directed towards studying the impact of human factors in the cardiac catheterization laboratory as well as the broader medical environment.

Pulmonary atresia with an intact ventricular septum typically occurs in patients with concordant atrioventricular and ventriculoarterial connections. When it does occur in patients with discordant connections, it is most frequently seen in association with congenitally corrected transposition. We present a rare case of transposition of the great arteries with a ventricular septal defect (VSD) detected in fetal life which evolved throughout pregnancy resulting in the development of pulmonary atresia and severe restriction of the VSD.

Background: Maximal left ventricular wall thickness (MLVWT) is a risk factor for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). In adults, the severity of left ventricular hypertrophy has a nonlinear relationship with SCD, but it is not known whether the same complex relationship is seen in childhood. The aim of this study was to describe the relationship between left ventricular hypertrophy and SCD risk in a large international pediatric HCM cohort. Methods: The study cohort comprised 1075 children (mean age, 10.2 years [±4.4]) diagnosed with HCM (1–16 years) from the International Paediatric Hypertrophic Cardiomyopathy Consortium. Anonymized, noninvasive clinical data were collected from baseline evaluation and follow-up, and 5-year estimated SCD risk was calculated (HCM Risk-Kids). Results: MLVWT Z score was Z scores were associated with heart failure symptoms, unexplained syncope, left ventricular outflow tract obstruction, left atrial dilatation, and nonsustained ventricular tachycardia. One hundred twenty-two patients (71.3%) with MLVWT Z score ≥20 had coexisting risk factors for SCD. Over a median follow-up of 4.9 years (interquartile range, 2.3–9.3), 115 (10.7%) had an SCD event. Freedom from SCD event at 5 years for those with MLVWT Z scores Z score, peaking at Z score +23. The presence of coexisting risk factors had a summative effect on risk. Conclusions: In children with HCM, an inverted U-shaped relationship exists between left ventricular hypertrophy and estimated SCD risk. The presence of additional risk factors has a summative effect on risk. While MLVWT is important for risk stratification, it should not be used either as a binary variable or in isolation to guide implantable cardioverter defibrillator implantation decisions in children with HCM.

The aim of this review is to highlight the strengths and limitations of major echocardiographic biventricular repair (BVR) prediction models for borderline left ventricle (LV) in complex congenital heart disease (CHD). A systematic search in the National Library of Medicine for Medical Subject Headings and free text terms including echocardiography, CHD, and scores, was performed. The search was refined by adding keywords for critical aortic stenosis (AS), borderline LV, complex left ventricular outflow tract (LVOT) obstruction, hypoplastic left heart syndrome/complex (HLHS/HLHC), and unbalanced atrio-ventricular septal defects (uAVSD). Fifteen studies were selected for the final analysis. We outlined what echocardiographic scores for different types of complex CHD with diminutive LV are available. Scores for CHD with LVOT obstruction including critical AS, HLHS/HLHC, and aortic arch hypoplasia have been validated and implemented by several studies. Scores for uAVSD with right ventricle (RV) dominance have also been established and implemented, the first being the atrioventricular valve index (AVVI). In addition to AVII, both LV/RV inflow angle and LV inflow index have all been validated for the prediction of BVR. We conclude with a discussion of limitations in the development and validation of each of these scores, including retrospective design during score development, heterogeneity in echocardiographic parameters evaluated, variability in the definition of outcomes, differences in adopted surgical and Interventional strategies, and institutional differences. Furthermore, scores developed in the past two decades may have little clinical relevance now. In summary, we provide a review of echocardiographic scores for BVR in complex CHD with a diminutive LV that may serve as a guide for use in modern clinical practice.

Nicolaides-Baraitser syndrome is a rare, neuro-developmental disorder caused by heterozygous pathogenic variants in the SMARCA2 gene, involved with chromatin regulation. Cardinal features include intellectual disability, short stature, microcephaly, triangular facies, sparse hair, brachydactyly, prominent interphalangeal joints and seizures. Genetic testing demonstrated a loss within SMARCA2 at 9p24.3 inclusive of basepairs 2094861_2141830 (hg19) in our patient. This case highlights a child with Nicolaides-Baraiter syndrome, a SMARCA2 gene deletion and a novel association of hypertrophic obstructive cardiomyopathy.

Acquired demyelinating syndromes of the central nervous system are rare disorders in childhood. Immune-mediated damage affects the myelin sheath of the optic nerves, brain and spinal cord. The majority are monophasic. Relapsing demyelinating syndromes include multiple sclerosis, aquaporin-4 antibody-associated disease and myelin oligodendrocyte glycoprotein antibody-associated disease. The relapsing syndromes are associated with gradual accrual of neurological deficits and cognitive impairment. In this review, we discuss the presentation, diagnosis and management of monophasic and relapsing acquired demyelinating syndromes. We highlight the fact that CNS autoantibody mediated disorders are distinct clinical entities separate to multiple sclerosis and discuss the treatment options and prognosis for each. Finally, we detail current available therapeutic drugs for paediatric demyelinating conditions and their adverse effects.

Kawasaki disease (KD), an acute, self-limiting, medium-sized arterial vasculitis, is now the most common cause of acquired heart disease in childhood in the developed world. In this review, we discuss the diagnosis of KD, predicting resistance to traditional therapy and treatment options in refractory or high-risk disease. We also highlight ongoing clinical trials and other potential avenues of research which may prove beneficial in managing children, especially those with resistant KD.

Introduction Sudden cardiac death is the most common cause of mortality in childhood onset hypertrophic cardiomyopathy. Identifying individuals at highest risk is therefore an essential part of clinical care but remains challenging. The 12 lead electrocardiogram (ECG) has been proposed as a useful tool for risk stratification and an ECG risk score has been proposed. However, this has not been independently validated and the ECG phenotype of childhood HCM has not been previously described. The aim of this study was to describe the ECG phenotype of childhood HCM in a large, international, multi-centre cohort and investigate its role in risk prediction for arrhythmic events. Methods Participants with an available baseline resting 12-lead ECG were identified from a large, international, multi-centre, retrospective cohort of patients aged less than 16 years fulfilling the diagnostic criteria for HCM (n=1029). Resting baseline ECG was evaluated and ECG variables were extracted. In addition, the ECG risk score based on 8 parameters (deviation in QRS axis, pathological T-wave inversion in limb or precordial leads, ST-segment depression, dominant S-wave in V4, limb-lead amplitude sum, 12-lead amplitude duration product and QTc) was calculated as previously described. The primary study endpoint was a composite outcome of major cardiac events (MACE) defined as SCD, resuscitated cardiac arrest, appropriate implantable cardioverter defibrillator therapy, or sustained ventricular tachycardia (VT) with haemodynamic compromise. The discriminatory performance of using an ECG risk score >5 to identify patients at increased risk of MACE at 5 years was determined using Harrell’s C-index. Results Of 356 patients with childhood HCM (68.9% male, mean age at presentation 10.1 ± 4.5 years), 347 (97.5%) had baseline ECG abnormalities such as: repolarization abnormalities (n=277, 77.8%), left ventricular hypertrophy (n=240. 67.6%), abnormal QRS axis (n=126, 35.4%) or QT prolongation (n=131, 36.8%). Over a median follow up of 3.9 years (IQR 2.0-7.7), 25 (7%) had an arrhythmic event, with an overall annual event rate of 1.38 (95% CI 0.93-2.04). No ECG variables were associated with 5-year MACE on univariable or multivariable Cox regression analysis. Of the 164 participants with an ECG score >5, 153 (93.3%) did not have a MACE within 5 years. Harrell’s C-index (the probability of correctly distinguishing between high and low risk patients using an ECG risk score threshold of >5) was 0.60 (95% CI 0.484-0.715) at 5 years. The corresponding positive and negative predictive values were 6.7% (95% CI 4.7 – 9.4%) and 96.9% (95% CI 94.2 – 98.4%). Conclusions In a large, international, multi-centre cohort of children with HCM, ECG abnormalities are common. No ECG characteristic, either in isolation or combined in the ECG risk score, was associated with 5-year MACE risk. This suggests that the role of the baseline ECG phenotype in improving risk stratification in childhood HCM is limited. Conflict of Interest None

Aims The 12-lead electrocardiogram (ECG) is routinely performed in children with hypertrophic cardiomyopathy (HCM). An ECG risk score has been suggested as a useful tool for risk stratification, but this has not been independently validated. This aim of this study was to describe the ECG phenotype of childhood HCM in a large, international, multi-centre cohort and investigate its role in risk prediction for arrhythmic events. Methods and results Data from 356 childhood HCM patients with a mean age of 10.1 years (±4.5) were collected from a retrospective, multi-centre international cohort. Three hundred and forty-seven (97.5%) patients had ECG abnormalities at baseline, most commonly repolarization abnormalities (n = 277, 77.8%); left ventricular hypertrophy (n = 240, 67.7%); abnormal QRS axis (n = 126, 35.4%); or QT prolongation (n = 131, 36.8%). Over a median follow-up of 3.9 years (interquartile range 2.0–7.7), 25 (7%) had an arrhythmic event, with an overall annual event rate of 1.38 (95% CI 0.93–2.04). No ECG variables were associated with 5-year arrhythmic event on univariable or multivariable analysis. The ECG risk score threshold of >5 had modest discriminatory ability [C-index 0.60 (95% CI 0.484–0.715)], with corresponding negative and positive predictive values of 96.7% and 6.7% Conclusion In a large, international, multi-centre cohort of childhood HCM, ECG abnormalities were common and varied. No ECG characteristic, either in isolation or combined in the previously described ECG risk score, was associated with 5-year sudden cardiac death risk. This suggests that the role of baseline ECG phenotype in improving risk stratification in childhood HCM is limited.

This is a case of a 14-year-old boy who attended the emergency department with fever, cough, and arthralgia. Examination revealed hepatomegaly and a continuous murmur. Blood cultures were positive on three separate occasions for meticillin-sensitive Staphylococcus aureus, and a diagnosis of infective endocarditis, with an intra-atrial thrombus complicating a coronary artery fistula, was made. The intracardiac thrombus was functioning as a septic nidus, and the patient had cavitating lung nodules likely representing septic emboli. The patient underwent thrombolytic therapy to eradicate the thrombus and recovered following a prolonged course of intravenous antibiotics and low-molecular weight heparin. Several months later, he electively underwent transcatheter device closure of the coronary artery fistula. This case discusses the definition and types of fistulae; the pathophysiology, presentation, and complications associated with this condition; the investigations and diagnosis; and finally the management options for patients with coronary artery fistulae. The nuances involved in the management of these cases are discussed, including the debate regarding indications for closure.

Optimal outcomes are as much influenced by critical decision making pathways as by the technical skill of the operator. The complexity and potential cognitive traps underlying critical decision making has long been recognized in the aviation and business communities, however, remains a largely subconscious, unexamined discipline amongst congenital cardiac interventionalists. Challenges to making good decisions in the catheterization laboratory include heuristics, biases, and cognitive traps. In this paper we discuss some of the more common decision making challenges encountered and we address potential solutions to such decision making with particular focus towards standardization.

The complexity and potential biases involved in decision making have long been recognised and examined in both the aviation and business industries. More recently, the medical community have started to explore this concept and its particular importance in our field. Paediatric cardiology is a rapidly expanding field and for many of the conditions we treat, there is limited evidence available to support our decision-making. Variability exists within decision-making in paediatric cardiology and this may influence outcomes. There are no validated tools available to support and examine consistent decision-making for various treatment strategies in children with congenital heart disease in a multidisciplinary cardiology and cardiothoracic institution. Our primary objective was to analyse the complexity of decision-making for children with cardiac conditions in the context of our joint cardiology and cardiothoracic conference (JCC). Two paediatric cardiologists acted as investigators by observing the weekly joint cardiology-cardiothoracic surgery conference and prospectively evaluating the degree of complexity of decision-making in the management of 107 sequential children with congenital heart disease discussed. Additionally, the group consensus on the same patients was prospectively assessed to compare this to the independent observers. Of 107 consecutive children discussed at our JCC conference 32 (27%) went on to receive surgical intervention, 20 (17%) underwent catheterisation and 65 (56%) received medical treatment. There were 53 (50%) cases rated as simple by one senior observer, while 54 (50%) were rated as complex to some degree. There was high inter-observer agreement with a Krippendorff's alpha of ≥ 0.8 between 2 observers and between 2 observers and the group consensus as a whole for grading of the complexity of decision-making. Different decisions were occasionally made on patients with the same data set. Discussions revisiting the same patient, in complex cases, resulted in different management decisions being reached in this series. Anchoring of decision-making was witnessed in certain cases. Potential application of decision making algorithms is discussed in making decisions in paediatric cardiology patients. Decision-making in our institution's joint cardiology-cardiothoracic conference proved to be complex in approximately half of our patients. Inconsistency in decision-making for patients with the same diagnosis, and different decisions made for the same complex patient at different time points confounds the reliability of the decision-making process. These novel data highlight the absence of evidence-based medicine for many decisions, occasional lack of consistency and the impact of anchoring, heuristics and other biases in complex cases. Validated decision-making algorithms may assist in providing consistency to decision-making in this setting.

Objective: To identify predictors of epilepsy and clinical relapses in children presenting with acute disseminated encephalomyelitis (ADEM). Methods: Children presenting with ADEM between 2005 and 2017 and tested clinically for MOG-Ab were identified from three tertiary paediatric neurology centres in the United Kingdom. Patients were followed up for a median of 6 years (range, 1–16 years). Results: A total of 74 children were studied (38 females; median age at first presentation: 4.5 years (range, 1.4–16 years)). MOG-Ab was positive in 50/74 (67.6%) of cases, and 27 (54%) of MOG-Ab positive children presented with a neurological relapse over time. MOG-Ab was more frequently positive in the relapsing group than in the monophasic group (27/31 vs 23/43; odds ratio 5.9 (95% CI: 1.8–19.7); p = 0.002). 16/74 (22%) children had seizures during the acute presentation with ADEM and 12/74 (16.2%) patients were diagnosed with post-ADEM epilepsy. The diagnosis of post-ADEM epilepsy was more frequently observed in children with relapsing disease than monophasic disease (10/31 vs 2/43; odds ratio 9.8 (95% confidence interval (CI): 2.0–48.7); p = 0.003), in children who had positive intrathecal oligoclonal bands than those with negative bands (4/7 vs 4/30; odds ratio 8.7 (95% CI: 1.4–54.0); p = 0.027) and in children who had positive MOG-Ab than negative MOG-Ab cases (11/12 vs 39/62; odds ratio 6.5 (95% CI:0.8–53.6); p = 0.051). Conclusion: A higher relapse rate and a greater risk of post-ADEM epilepsy in children with MOG-Ab-associated disease may indicate a chronic disease with immune-mediated seizures in these children.

Multiple sclerosis is a chronic immune-mediated demyelinating disease of the central nervous system. The diagnosis of multiple sclerosis in children, as in adults, requires evidence of dissemination of inflammatory activity in more than one location in the central nervous system (dissemination in space) and recurrent disease over time (dissemination in time). The identification of myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) and aquaporin-A antibodies (AQP4-Ab), and the subsequent discovery of their pathogenic mechanisms, have led to a shift in the classification of relapsing demyelinating syndromes. This is reflected in the 2017 revised criteria for the diagnosis of multiple sclerosis, which emphasizes the exclusion of multiple sclerosis mimics and aims to enable earlier diagnosis and thus treatment initiation. The long-term efficacy of individual therapies initiated in children with multiple sclerosis is hard to evaluate, owing to the small numbers of patients who have the disease, the relatively high number of patients who switch therapy, and the need for long follow-up studies. Nevertheless, an improvement in prognosis with a globally reduced annual relapse rate in children with multiple sclerosis is now observed compared with the pretreatment era, indicating a possible long-term effect of therapies. Given the higher relapse rate in children compared with adults, and the impact multiple sclerosis has on cognition in the developing brain, there is a question whether rapid escalation or potent agents should be used in children, while the short- and long-term safety profiles of these drugs are being established. With the results of the first randomized controlled trial of fingolimod versus interferon-β1a in paediatric multiple sclerosis published in 2018 and several clinical trials underway, there is hope for further progress in the field of paediatric multiple sclerosis. WHAT THIS PAPER ADDS: Early and accurate diagnosis of multiple sclerosis is crucial. The discovery of antibody-mediated demyelination has changed the diagnosis and management of relapsing demyelination syndromes. Traditional escalation therapy is being challenged by induction therapy.ESCLEROSIS MÚLTIPLE PEDIÁTRICA: UNA NUEVA ERA EN EL DIAGNÓSTICO Y TRATAMIENTO: La esclerosis múltiple es una enfermedad desmielinizante crónica mediada por el sistema inmunitario del sistema nervioso central. El diagnóstico de esclerosis múltiple en niños, como en adultos, requiere evidencia de diseminación de actividad inflamatoria en más de un lugar en el sistema nervioso central (diseminación en el espacio) y enfermedad recurrente a lo largo del tiempo (diseminación en el tiempo). La identificación de los anticuerpos de la glicoproteína oligodendrocítica de la mielina (MOG-Ab) y los anticuerpos de la acuaporina-A (AQP4-Ab), y el posterior descubrimiento de sus mecanismos patógenos, han conducido a un cambio en la clasificación de los síndromes desmielinizantes recurrentes. Esto se refleja en los criterios revisados ​​de 2017 para el diagnóstico de esclerosis múltiple, que enfatiza la exclusión de los imitadores de la esclerosis múltiple y tiene como objetivo permitir un diagnóstico más temprano y, por lo tanto, el inicio del tratamiento. La eficacia a largo plazo de las terapias individuales iniciadas en niños con esclerosis múltiple es difícil de evaluar, debido a la pequeña cantidad de pacientes que tienen la enfermedad, la cantidad relativamente alta de pacientes que cambian de terapia y la necesidad de estudios de seguimiento prolongados. Sin embargo, ahora se observa una mejora en el pronóstico con una tasa de recaída anual globalmente reducida en niños con esclerosis múltiple en comparación con la era anterior al tratamiento previo, lo que indica un posible efecto a largo plazo de las terapias. Debido a la mayor tasa de recaída en niños en comparación con los adultos, y el impacto que tiene la esclerosis múltiple en la cognición en el cerebro en desarrollo, existe la duda de si se deben usar agentes de aumento rápido o potentes en niños, mientras que los perfiles de seguridad a corto y largo plazo de estos medicamentos se están estableciendo. Con los resultados del primer ensayo controlado aleatorio de fingolimod versus interferón-β1a en esclerosis múltiple pediátrica publicado en 2018 y varios ensayos clínicos en curso, existe la esperanza de un mayor progreso en el campo de la esclerosis múltiple pediátrica.ESCLEROSE MÚLTIPLA PEDIÁTRICA: UMA NOVA ERA NO DIAGNÓSTICO E TRATAMENTO: A esclerose múltipla é uma doença desmielinizante imunomediada crônica do sistema nervoso central. O diagnóstico de esclerose múltipla em crianças, como em adultos, exige evidência de disseminação da atividade inflamatória em mais de um local no sistema nervoso central (disseminação no espaço) e doença recorrente ao longo do tempo (disseminação no tempo). A identificação de anticorpos anti-glicoproteína de mielina do oligodendrócito (MOG-Ab) e anticorpos anti-aquaporina A (AQP4-Ab), e a subsequente descoberta de seus mecanismos patogênicos, levaram a uma mudança na classificação das síndromes desmielinizantes recidivantes. Isso se reflete nos critérios revisados de 2017 para o diagnóstico de esclerose múltipla, que enfatizam a exclusão de transtornos que mimetizam esclerose múltipla e visam permitir o diagnóstico precoce e, portanto, o início do tratamento. É difícil avaliar a eficácia a longo prazo de terapias individuais iniciadas em crianças com esclerose múltipla, devido ao pequeno número de pacientes que têm a doença, o número relativamente alto de pacientes que trocam de terapia e a necessidade de estudos de acompanhamento a longo prazo. No entanto, uma melhora no prognóstico com uma taxa de recaída anual globalmente reduzida em crianças com esclerose múltipla é agora observada em comparação com a era pré-tratamento, indicando um possível efeito a longo prazo das terapias. Dada a maior taxa de recaída em crianças em comparação com adultos, e o impacto da esclerose múltipla na cognição no cérebro em desenvolvimento, há uma questão se a escalada rápida ou agentes potentes devem ser usados em crianças, enquanto os perfis de segurança de curto e longo prazo destas drogas estão sendo estabelecidos. Com os resultados do primeiro estudo controlado randomizado de fingolimode versus interferon-β1a na esclerose múltipla pediátrica publicado em 2018 e vários ensaios clínicos em andamento, há esperança de mais progressos no campo da esclerose múltipla pediátrica.

AIM: Our objectives were to evaluate the utility of measuring myelin oligodendrocyte glycoprotein (MOG) and aquaporin-4 (AQP4) antibodies (Ab) in clinical practice and describe their associated neurological phenotypes in children. METHOD: Between 2012 and 2017, 371 children with suspected acquired demyelinating syndromes (ADS) seen in three tertiary centres were tested for MOG-Ab and AQP4-Ab. Medical notes were retrospectively reviewed, and clinical and demographic data compiled. Clinical phenotyping was performed blinded to the antibody results. RESULTS: After review, 237 of the 371 were diagnosed with ADS. Of these, 76 out of 237 (32.1%) were MOG-Ab positive and 14 out of 237 (5.9%) were AQP4-Ab positive. None were positive for both autoantibodies. All 134 patients with non-ADS were negative for MOG-Ab. MOG-Ab were identified in 45 out of 70 (64.3%) patients presenting with acute disseminated encephalomyelitis (ADEM) and in 24 out of 25 patients with relapsing ADEM. Thirty-six out of 75 (48%) MOG-Ab positive patients relapsed. Of the 33 children with neuromyelitis optic spectrum disorder, 14 were AQP4-Ab positive, 13 were MOG-Ab positive, and 6 were seronegative. Of the children with longitudinal samples, 8 out of 13 AQP4-Ab remained positive during the disease course compared to 35 out of 43 MOG-Ab (13/16 monophasic and 22/27 relapsing). INTERPRETATION: Myelin oligodendrocyte glycoprotein antibodies were identified in a third of children with ADS. Almost half of the MOG-Ab positive children relapsed and the majority of them remained antibody positive over 4-years follow-up. WHAT THIS PAPER ADDS: Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) are highly specific for acquired demyelinating syndromes (ADS). Myelin oligodendrocyte glycoprotein antibodies are not identified in children with peripheral demyelination or genetic leukodystrophies/hypomyelination. Up to 48% of MOG-Ab ADS paediatric patients relapse, higher than previously thought. Seroconversion to MOG-Ab negative status is infrequent; patients may test MOG-Ab positive at follow-up sampling even when asymptomatic. Myelin oligodendrocyte glycoprotein antibodies status should only be used in conjunction with the clinical information to guide maintenance therapy.

Hidden traps in decision making have been long recognised in the behavioural economics community. Yet we spend very limited, if any time, analysing our decision-making processes in medicine and paediatric cardiology. Systems 1 and 2 thought processes differentiate between rapid emotional thoughts and slow deliberate rational thoughts. For fairly clear cut medical decisions, in-depth analysis may not be needed, but in our field of paediatric cardiology it is not uncommon for challenging cases and occasionally 'simple' cases to generate significant debate and uncertainty as to the best decision. Although morbidity and mortality meetings frequently highlight poor outcomes for our patients, they often neglect to analyse the process of thought which underlined those decisions taken. This article attempts to review commonly acknowledged traps in decision making in the behavioural economics world to ascertain whether these heuristics translate to decision making in the paediatric cardiology environment. We also discuss potential individual and collective solutions to pitfalls in decision making.

Importance: Sudden cardiac death (SCD) is the most common mode of death in childhood hypertrophic cardiomyopathy (HCM), but there is no validated algorithm to identify those at highest risk.Objective: To develop and validate an SCD risk prediction model that provides individualized risk estimates.Design, Setting, and Participants: A prognostic model was developed from a retrospective, multicenter, longitudinal cohort study of 1024 consecutively evaluated patients aged 16 years or younger with HCM. The study was conducted from January 1, 1970, to December 31, 2017.Exposures: The model was developed using preselected predictor variables (unexplained syncope, maximal left-ventricular wall thickness, left atrial diameter, left-ventricular outflow tract gradient, and nonsustained ventricular tachycardia) identified from the literature and internally validated using bootstrapping.Main Outcomes and Measures: A composite outcome of SCD or an equivalent event (aborted cardiac arrest, appropriate implantable cardioverter defibrillator therapy, or sustained ventricular tachycardia associated with hemodynamic compromise).Results: Of the 1024 patients included in the study, 699 were boys (68.3%); mean (interquartile range [IQR]) age was 11 (7-14) years. Over a median follow-up of 5.3 years (IQR, 2.6-8.3; total patient years, 5984), 89 patients (8.7%) died suddenly or had an equivalent event (annual event rate, 1.49; 95% CI, 1.15-1.92). The pediatric model was developed using preselected variables to predict the risk of SCD. The model's ability to predict risk at 5 years was validated; the C statistic was 0.69 (95% CI, 0.66-0.72), and the calibration slope was 0.98 (95%, CI 0.59-1.38). For every 10 implantable cardioverter defibrillators implanted in patients with 6% or more of a 5-year SCD risk, 1 patient may potentially be saved from SCD at 5 years.Conclusions and Relevance: This new, validated risk stratification model for SCD in childhood HCM may provide individualized estimates of risk at 5 years using readily obtained clinical risk factors. External validation studies are required to demonstrate the accuracy of this model's predictions in diverse patient populations.

AIMS To assess students’ attitudes towards research; awareness of the importance of research in their future career; awareness of research opportunities; ability to carry out literature appraisals. METHODS Students enrolled in the School of Medicine in UCD during the 2010 academic year were invited to participate in an online anonymous standardised questionnaire. An exemption from ethical approval was granted by UCD. Questions were primarily closed-ended, 5 of which involved a 4-point Likert scale, and students could use free text to answer certain questions such as ‘What is your understanding of evidence based medicine?’ RESULTS Responses were received from 180 students, of whom 16% had previously participated in research. Surprisingly 83% did not feel adequately aware of research opportunities . The projects they were most aware of were Health Resource Board (HRB) scholarships and Student Summer Research Awards (SSRA), and 40% said that they would like to participate in research but did not know how to get involved. The strongest motivating factor to participate in research was the potential benefit for future career prospects, and 36% of students said that an inspiring mentor would most encourage them to do research, ahead of prizes, monetary incentives or academic credits. The most common disincentive was ‘difficulty balancing with academic commitments’ (30%), followed by ‘lack of awareness of research opportunities’ ( 25%). A third of students thought that an intercalated BSc was a good idea, however only 25% were aware that UCD offers this option, and only 11% thought that the medical school provides enough information about it. Two thirds of students felt they understood the term ‘ critical appraisal’ and 23% judged themselves capable of carrying it out. Almost all (88%) students felt they needed more guidance in interpretation of the literature. CONCLUSIONS Medical students show an interest in participating in research and are aware of its importance, but do not feel they are made appropriately aware of research opportunities. Students are generally unaware of the option of an intercalated degree. Finally, most students do not feel they have the ability to critically appraise literature.

BackgroundUnresectable cholangiocarcinoma (CCA) has a dismal prognosis. Initial studies of orthotopic liver transplantation (OLT) alone for CCA yielded disappointing outcomes. The Mayo Clinic demonstrated long-term survival using neoadjuvant chemoradiotherapy followed by OLT in selected patients with unresectable CCA. This study reports the Irish National Liver Transplant Programme experience of neoadjuvant therapy and OLT for unresectable CCA.Materials and MethodsTwenty-seven patients with CCA were selected for neoadjuvant chemoradiotherapy in a single centre from October 2004 to September 2011. Patients were given brachytherapy, external beam radiotherapy and 5-fluorouracil (5-Fu), followed by liver transplantation if progression free (20 patients).ResultsTwenty progression-free patients after neoadjuvant therapy underwent OLT. Hospital mortality was 20%. Of the 16 patients who left hospital, survival rates were 94% and 61% at 1 and 4 years. Seven patients developed recurrent disease and died at intervals of 10–58 months after OLT, whereas 9 are disease free with a median follow-up of 37 months (18–76). Predictors of disease recurrence were a tumour in explant specimen and high CA 19.9 levels.DiscussionIn selected patients with unresectable CCA, long-term survival can be achieved using neoadjuvant chemoradiotherapy and OLT although short-term mortality is high. Prospective international registries may aid patient selection and refinement of neoadjuvant regimens.