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Shwachman-Diamond syndrome (SDS) is an autosomal recessive disorder characterised by skeletal dysplasia, exocrine pancreatic insufficiency and bone marrow failure. Various other conditions, such as hepatopathy and failure to thrive have been associated with SDS. A retrospective study was conducted to describe mutations, clinical features, and the immunological profile of 11 Belgian patients with genetically confirmed diagnosis of SDS. This study confirms the existing understanding of the classical features of SDS although the typical triad was present in only six out of nine fully studied patients. The following important observations are made in this cohort. Four out of eleven patients were misdiagnosed as having Asphyxiating Thoracic Dystrophy (Jeune syndrome) because of severe thoracic dystrophy. Another two patients presented with unexplained episodes of symptomatic hypoglycaemia. The immunological phenotype was heterogeneous although laboratory abnormalities were noticed in eight out of ten patients assessed. Three patients experienced a life threatening viral infection (respiratory syncytial virus, cytomegalovirus (CMV) and rotavirus). In one patient, CMV infection caused an episode of haemophagocytic lymphohistiocytosis. One patient has bronchiectasis at the age of 3 years due to recurrent respiratory tract infections. These findings strengthen the suspicion of an abnormal immune system in SDS. Liver anomalies, usually described as benign and transitory in SDS patients, were severe in two patients of the cohort. One patient developed hepatopulmonary syndrome. The findings in this national cohort of SDS patients could contribute to the prevention of misdiagnosis in the future and enable more rapid recognition of certain severe complications. [ABSTRACT FROM AUTHOR]

The authors explored this sensitive topic, by surveying the self-reported attitudes of neonatologists and neonatal nurses in the Flanders region of Belgium. Marie Friedel, paediatric nurse; Dr Marleen Renard, paediatrician, Prof. Hugo Devlieger neonatologist; Prof. Gaston Verellen, paediatrician, neonatologist, professor emeritus. Neonatologists and neonatal nurses have positive attitudes towards perinatal end-of-life decisions, a nationwide survey. [Extracted from the article]

Objective: The c.1998delinsTTCT variant in the RET gene (codon 666) is linked to medullary thyroid carcinoma in Belgium. We aimed to study the clinical phenotype and the age-dependent penetrance in predictive variant carriers. Design: Retrospective study of index patients and predictive variant carriers, identified through familial cascade testing between 2001 and 2020. Results: The total cohort comprised 119 patients: 15 index patients, 102 heterozygous, and 2 homozygous predictive variant carriers. Among heterozygous carriers, high suspicion of clinical disease was present in 25 patients at initial evaluation and in 3 patients during follow-up. No high suspicion of clinical disease was observed during surveillance in 56 patients, and 18 patients did not proceed to screening for clinical disease. Compared to index patients, surgically treated heterozygous predictive variant carriers had a lower presurgical basal calcitonin, a lower disease stage, less need for adjuvant therapy, and higher chances of remission. In heterozygous carriers, median age at developing high suspicion of disease is 52 years (range 7-75), with a predicted penetrance of 62% (9% SE) at the age of 70 years. Two patients were identified with pheochromocytoma and 1 patient with primary hyperparathyroidism. The 2 homozygous predictive variant carriers presented with higher disease severity at first clinical evaluation. Conclusion: The c.1998delinsTTCT variant in the RET gene is pathogenic and associated with a moderate risk for medullary thyroid carcinoma and rarely with other multiple endocrine neoplasia type 2A (MEN2A) manifestations. Active surveillance is a possible option in heterozygous gene carriers with a negative first clinical evaluation. [ABSTRACT FROM AUTHOR]

Purpose: Despite its limitations, [123I]MIBG scintigraphy has been the standard for human norepinephrine transporter (hNET) imaging for several decades. Recently, [18F]MFBG has emerged as a promising PET alternative. This prospective trial aimed to evaluate safety, biodistribution, tumour lesion pharmacokinetics, and lesion targeting of [18F]MFBG and perform a head-to-head comparison with [123I]MIBG in neural crest tumour patients. Methods: Six neural crest tumour patients (4 phaeochromocytoma, 1 paraganglioma, 1 neuroblastoma) with a recent routine clinical [123I]MIBG scintigraphy (interval: − 37–75 days) were included. Adult patients (n = 5) underwent a 30-min dynamic PET, followed by 3 whole-body PET/CT scans at 60, 120, and 180 min after injection of 4 MBq/kg [18F]MFBG. One minor participant underwent a single whole-body PET/CT at 60 min after administration of 2 MBq/kg [18F]MFBG. Normal organ uptake (SUVmean) and lesion uptake (SUVmax; tumour-to-background ratio (TBR)) were measured. Regional distribution volumes (VT) were estimated using a Logan graphical analysis in up to 6 lesions per patient. A lesion-by-lesion analysis was performed to compare detection ratios (DR), i.e. fraction of detected lesions, between [18F]MFBG and [123I]MIBG. Results: [18F]MFBG was safe and well tolerated. Its biodistribution was overall similar to that of [123I]MIBG, with prominent uptake in the salivary glands, liver, left ventricle wall and adrenals, and mainly urinary excretion. In the phaeochromocytoma subgroup, the median VT was 37.4 mL/cm3 (range: 18.0–144.8) with an excellent correlation between VT and SUVmean at all 3 time points (R2: 0.92–0.94). Mean lesion SUVmax and TBR at 1 h after injection were 19.3 ± 10.7 and 23.6 ± 8.4, respectively. All lesions detected with [123I]MIBG were also observed with [18F]MFBG. The mean DR with [123I]MIBG was significantly lower than with [18F]MFBG (61.0% ± 26.7% vs. 99.8% ± 0.5% at 1 h; p = 0.043). Conclusion: [18F]MFBG is a promising hNET imaging agent with favourable imaging characteristics and improved lesion targeting compared with [123I]MIBG scintigraphy. Trial registration: Clinicaltrials.gov: NCT04258592 (Registered: 06 February 2020), EudraCT: 2019-003872-37A. [ABSTRACT FROM AUTHOR]

Regulatory decisions on paediatric investigation plans (PIPs) aim at making effective and safe medicines timely available for children with high unmet medical need. At the same time, scientific knowledge progresses continuously leading frequently to the identification of new molecular targets in the therapeutic area of oncology. This, together with further efforts to optimise next generation medicines, results in novel innovative products in development pipelines. In the context of global regulatory development requirements for these growing pipelines of innovative products (e.g. US RACE for children Act), it is an increasing challenge to complete development efforts in paediatric oncology, a therapeutic area of rare and life-threatening diseases with high unmet needs. Regulators recognise feasibility challenges of the regulatory obligations in this context. Here, we explain the EU regulatory decision making strategy applied to paediatric oncology, which aims fostering evidence generation to support developments based on needs and robust science. Because there is a plethora of products under development within given classes of or within cancer types, priorities need to be identified and updated as evidence evolves. This also includes identifying the need for third or fourth generation products to secure focused and accelerated drug development. An agreed PIP, as a plan, is a living document which can be modified in light of new evidence. For this to be successful, input from the various relevant stakeholders, i.e. patients/parents, clinicians and investigators is required. To efficiently obtain this input, the EMA is co-organising with ACCELERATE oncology stakeholder engagement platform meetings. • Regulatory decision-making in the context of product development life cycle. • PIP as a plan, allowing for evidence generation, able to be modified. • Fostering collaborative development environment, not competitive. • Need to identify priorities based on science. • Collaboration among all stakeholders key, as exemplified by ACCELERATE. [ABSTRACT FROM AUTHOR]

Cites a study conducted by researchers in Belgium which found that peripheral primitive neuroectodermal tumor (PNET)/ Ewing's sarcoma (ES) of the central nervous system is extremely rare. Distinction of PNET and ES from central PNET and other small blue round cell tumors; Expression of epithelial markers posturing an important diagnostic problem with synovial sarcoma; Importance of genetic analysis in the distinction from other small blue round cell tumors.

Long-term follow-up (LTFU) care for childhood, adolescent, and young adult (CAYA) cancer survivors is essential to preserve health and quality of life (QoL). Evidence-based guidelines are needed to inform optimal surveillance strategies, but many topics are yet to be addressed by the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG). Therefore, the PanCareFollowUp Recommendations Working Group collaborated with stakeholders to develop European harmonised recommendations in anticipation of evidence-based IGHG guidelines. The PanCareFollowUp Recommendations Working Group, consisting of 23 late effects specialists, researchers, and survivor representatives from nine countries, collaborated in the first Europe-wide effort to provide unified recommendations in anticipation of evidence-based guidelines. A pragmatic methodology was used to define recommendations for topics where no evidence-based IGHG recommendations exist. The objective was to describe the surveillance requirements for high-quality care while balancing the different infrastructures and resources across European health care systems. The process included two face-to-face meetings and an external consultation round involving 18 experts from 14 countries. Twenty-five harmonised recommendations for LTFU care were developed collaboratively and address topics requiring awareness only (n = 6), awareness, history and/or physical examination (n = 9), or additional surveillance tests (n = 10). The PanCareFollowUp Recommendations, representing a unique agreement across European stakeholders, emphasise awareness among survivors and health care providers in addition to tailored clinical evaluation and/or surveillance tests. They include existing IGHG guidelines and additional recommendations developed by a pragmatic methodology and will be used in the Horizon 2020–funded PanCareFollowUp project to improve health and QoL of CAYA cancer survivors. • Long-term follow-up care is important for survivors of childhood cancer. • Evidence-based guidelines to direct care are essential, but lacking for many topics. • We developed harmonised surveillance recommendations to bridge the gap. • Survivor representatives were involved in the formulation of recommendations. [ABSTRACT FROM AUTHOR]

Introduction: An ovarian Sertoli cell tumour was detected in a 4-year-old girl with gonadotrophin-independent precocious puberty. Such gonadal tumours can be associated with Peutz-Jeghers syndrome, caused by mutations in the STK11 gene. We have therefore sequenced the STK11 gene.Results: Mutation analysis revealed a nonsense mutation in exon 1 (c.130A>T;p.Lys44X) of the SKT11 gene, which resulted in a truncated, inactive protein. The mutation was heterozygous in patient's lymphocytes and almost homozygous in the tumour, indicating loss of heterozygosity.Conclusion: This is the first report of a STK11 germline mutation in a girl with an ovarian Sertoli cell tumour. It remains to be shown whether this particular mutation predisposes the patient to the development of ovarian tumours. [ABSTRACT FROM AUTHOR]

The authors convey their concerns about a Belgian euthanasia law and its effect on the practises of Belgian paediatric palliative care teams. Topics covered include extension of an existing euthanasia law for adults to minors in February 2014, euthanasia and palliative care as the Belgian model of integral end-of-life care, and cultural differences in perceptions and practices recognised in the White Paper from the European Association of Palliative Care.

Background: In childhood acute lymphoblastic leukemia (ALL), radiotherapy for CNS prophylaxis is not used in frontline therapy anymore. Standard treatment for ALL nowadays consists of polychemotherapy. Therefore, assessment of potential chemotherapy-induced cognitive side effects becomes important. Although neurotoxicity was demonstrated in cross-sectional studies, longitudinal studies remain scarce.Procedure: We evaluated intellectual development of 94 pediatric ALL patients between 1990 and 1997, diagnosed before the age of 12 years, treated according to the European Organisation for Research and Treatment of Cancer Children's Leukemia Group 58881 protocol. Three assessments of the Wechsler Intelligence Scale for Children Revised were performed since diagnosis, according to age. Using repeated measures regression analysis, we investigated the effect of gender (low versus increased) risk group, parents' education, age at diagnosis, intelligence quotient (IQ) subscale (verbal (VIQ) versus performance (PIQ) intelligence), and test session.Results: PIQ scores were lower than VIQ at baseline (-5.3 points on average, p = 0.0032), yet PIQ increased more strongly (PIQ: +3.9 points per test session; VIQ: +0.8, p = 0.0079), so this baseline difference disappeared (p = 0.0079). There were no clear effects of gender (girls: +0.6 points; p = 0.78) or risk group (low risk: +1.5 points; p = 0.49), but IQ scores were higher when one parent had followed higher education (+9.5 points, p < 0.0001). Finally, diagnosis at younger age predicted lower IQ scores (-1.3 points per year, p = 0.0009).Conclusion: Given that IQ scores did not decline, our findings demonstrate a stable pattern. However, the lower PIQ scores at baseline may indicate that performance functioning is vulnerable to acute neurotoxicity. Also, lower scores for younger patients highlight the stronger impact of the disease and/or treatment at younger age.Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Mucopolysaccharidosis type l-Hurler syndrome (MPS-IH) is a lysosomal storage disease characterized by multisystem morbidity and death in early childhood. Although hematopoietic cell transplantation (HCT) has been performed in these patients for more than 30 years, large studies on the long-term outcome of patients with MPS-IH after HCT are lacking. The goal of this international study was to identify predictors of the long-term outcome of patients with MPS-IH after successful HCT. Two hundred seventeen patients with MPS-IH successfully engrafted with a median follow-up age of 9.2 years were included in this retrospective analysis. Primary endpoints were neurodevelopmental outcomes and growth. Secondary endpoints included neurologic, orthopedic, cardiac, respiratory, ophthalmologic, audiologic, and endocrinologic outcomes. Considerable residual disease burden was observed in the majority of the transplanted patients with MPS-IH, with high variability between patients. Preservation of cognitive function at HCT and a younger age at transplantation were major predictors for superior cognitive development posttransplant. A normal a-L-iduronidase enzyme level obtained post-HCT was another highly significant predictor for superior long-term outcome in most organ systems. The long-term prognosis of patients with MPS-IH receiving HCT can be improved by reducing the age at HCT through earlier diagnosis, as well as using exclusively noncarrier donors and achieving complete donor chimerism. [ABSTRACT FROM AUTHOR]

Hematopoietic stem cell and solid organ transplant recipients diagnosed with biopsy-confirmed posttransplant lymphoproliferative disorder (PTLD) at our institution from 1989 to 2010 were identified. Patient-, transplant- and disease-related characteristics, prognostic factors and outcome were collected and analyzed. One hundred and forty biopsy-proven cases of PTLD were included. Overall incidence in the transplant population was 2.12%, with heart transplant recipients carrying the highest risk. Most PTLDs were monomorphic (82%), with diffuse large B-cell lymphoma being the most frequent subtype. The majority of cases (70.7%) occurred > 1 year posttransplant, and 66% were Epstein-Barr virus positive. Following initial therapy the overall response rate was 68.5%. Three-year relapse-free and overall survivals were 59% and 49%, respectively. At last follow-up, 44% of the patients were alive. Multivariable analysis identified several classical lymphoma-specific poor prognostic factors for the different outcome measures. The value of the International Prognostic Index was confirmed in our analysis. [ABSTRACT FROM AUTHOR]

Summary: Background: Neurofibromatosis type 1 is a common genetic disorder characterised by neurocutaneous manifestations and cognitive and behavioural problems. Statins were shown to reduce analogous learning deficits in a mouse model of the disease, but a short-term trial in humans was inconclusive. We aimed to assess the use of simvastatin for the improvement of cognitive and behavioural deficits in children with neurofibromatosis type 1 for 12 months. Methods: In this randomised, double-masked, placebo-controlled trial, we recruited children with genetically confirmed neurofibromatosis type 1 aged 8–16 years from two national referral centres in the Netherlands and Belgium. Those with symptomatic CNS abnormalities or on neurotropic medication, including stimulants, were excluded. Eligible patients were randomly assigned (1:1) via a computer-generated, permuted-block list to simvastatin (10 mg per day in month 1, 20 mg per day in month 2, and 20–40 mg per day in months 3–12) or placebo for 12 months. Investigators, participants, and parents were masked to treatment assignment. Primary outcome measures were full-scale intelligence (Wechsler intelligence scale for children), attention problems (child behaviour checklist, parent-rated [CBCL]), and internalising behavioural problems (CBCL). We did intention-to-treat analyses (of all patients who had outcome data) using linear regression of the 12 month outcome scores, adjusted for baseline performance. This trial is registered with the Netherlands Trial Register, number NTR2150. Findings: We randomly assigned 84 children to a treatment group (43 to simvastatin, 41 to placebo) between March 9, 2010, and March 6, 2012. We did not assess outcomes in two patients in the placebo group because they needed additional drug therapy. Simvastatin for 12 months had no effect on full-scale intelligence (treatment effect compared with placebo −1·3 IQ points [95% CI −3·8 to 1·3]; p=0·33), attention problems (–1·6 T-score points [–4·3 to 1·0]; p=0·23), and internalising behavioural problems (–0·1 T-score points [–3·3 to 3·1]; p=0·96). 38 (88%) of 43 patients on simvastatin and 39 (95%) of 41 patients on placebo reported adverse events, which were serious in two and four patients, respectively. Interpretation: 12 month simvastatin treatment did not ameliorate cognitive deficits or behavioural problems in children with neurofibromatosis type 1. The use of 20–40 mg simvastatin per day for cognitive enhancement in children with neurofibromatosis type 1 is not recommended. Funding: The Netherlands Organization for Health Research and Development (ZonMw), Research Foundation Flanders (FWO-Vlaanderen), Marguerite-Marie Delacroix Foundation, and the Dutch Neurofibromatosis Association (NFVN). [Copyright &y& Elsevier]

Background: Olmsted syndrome is a rare congenital skin disorder presenting with periorifical hyperkeratotic lesions and mutilating palmoplantar keratoderma, which is often associated with infections of the keratotic area. A recent study identified de novo mutations causing constitutive activation of TRPV3 as a cause of the keratotic manifestations of Olmsted syndrome. Methods: Genetic, clinical and immunological profiling was performed on a case study patient with the clinical diagnosis of Olmsted syndrome. Results: The patient was found to harbour a previously undescribed 1718G-C transversion in TRPV3, causing a G573A point mutation. In depth clinical and immunological analysis found multiple indicators of immune dysregulation, including frequent dermal infections, inflammatory infiltrate in the affected skin, hyper IgE production and elevated follicular T cells and eosinophils in the peripheral blood. Conclusions: These results provide the first comprehensive assessment of the immunological features of Olmsted syndrome. The systemic phenotype of hyper IgE and persistent eosinophilia suggest a primary or secondary role of immunological processes in the pathogenesis of Olmsted syndrome, and have important clinical consequences with regard to the treatment of Olmsted syndrome patients. [ABSTRACT FROM AUTHOR]

Abstract: We analyzed the long-term outcomes of pediatric patients registered in the European Group for Blood and Marrow Transplantation database who underwent hematopoietic stem cell transplantation (HSCT) for severe treatment refractory autoimmune cytopenia. With a median follow-up of 100 months, event-free survival was 54% overall, with no significant difference between allogeneic HSCT (n = 15) and autologous HSCT (n = 7) recipients (58% versus 42%; P = .50). Despite a trend toward failure of response or relapse after autologous HSCT compared with allogeneic HSCT, the difference was not significant (43% versus 13%; P = .30). Treatment-related mortality was high in both HSCT groups (29% and 16%; P = .09). Based on the limited numbers of subjects in this retrospective analysis, both allogeneic and autologous HSCT may induce complete and persistent responses in approximately one-half of pediatric patients with severe refractory autoimmune cytopenia, although treatment-related toxicity is high. [Copyright &y& Elsevier]

To describe the incidence, risk factors, and treatment of autoimmune diseases (ADs) occurring after cord blood transplantation (CBT), we analyzed both CBT recipients reported to EUROCORD who had developed at least 1 new AD and those who had not. Fifty-two of 726 reported patients developed at least 1 AD within 212 days (range, 27-4267) after CBT Cumulative incidence of ADs after CBT was 5.0% ± 1% at 1 year and 6.6% ± 1% at 5 years. Patients developing ADs were younger and had more nonmalig-nant diseases (P < .001). ADs target hematopoietic (autoimmune hemolytic anemia, n = 20; Evans syndrome, n = 9; autoimmune thrombocytopenia, n = 11; and immune neutropenia, n = 1) and other tissues (thyroiditis, n = 3; psoriasis, n = 2; Graves disease, n = 1; membranous glomerulonephritis, n = 2; rheumatoid arthritis, n = 1; ulcerative colitis, n = 1; and systemic lupus erythematosus, n = 1). Four patients developed 2 ADs (3 cases of immune thrombocytopenia followed by autoimmune hemolytic anemia and 1 Evans syndrome with rheumatoid arthritis). By multivariate analysis, the main risk factor for developing an AD was nonmalignant disease as an indication for CBT (P = .0001). Hematologic ADs were most often treated with steroids, rituximab, and cyclosporine. With a median follow-up of 26 months (range, 2-91), 6 of 52 patients died as a consequence of ADs. We conclude that CBT may be followed by potentially life-threatening, mainly hematologic ADs. [ABSTRACT FROM AUTHOR]

Aim: Hepatoblastoma (HB), the most common pediatric malignant liver tumor, is treated with chemotherapy to facilitate surgical resection. Previous studies suggest that HB acquires chemoresistance via increased expression of multidrug resistance protein 1 (MDR1, ABCC1). There is no well established evidence that this also occurs in the clinical setting and little is known about the effects of chemotherapeutic treatments on HB in situ. Methods: Clinical and histopathological features and expression patterns of ABC transporters in diagnostic needle biopsies from 7 HBs taken before chemotherapy were compared with those in surgically resected tumors. To understand the mechanism s leading to chemoresistance we also investigated the involvement of hypoxia on protein expression and functional activity of drug transporters (BCRP and MDR1) in cultures of HepG2 human HB cells. Results: We found that chemotherapeutical treatment of HBs led to an increased expression of the breast cancer resistance protein (BCRP, ABCG2) in all patients studied. There was no change in the expression pattern of MDR1 or other ABC transporters. Chemotherapy-induced specific vascular abnormalities associated with areas of necrosis and fibrosis were seen in all cases, suggesting tumor hypoxia. The observations of increased BCRP expression in hypoxic areas of three-dimensional HepG2 aggregates and the enhanced BCRP function in monolayer cultures of HepG2 cells under hypoxic conditions, support a role for hypoxia in enhanced BCRP expression. Conclusions: Chemotherapeutical treatment of HB leads to vascular alterations that modify the tumor microenvironment, and increased BCRP expression in which hypoxia might play a role. No evidence was found for upregulation of MDR1 in HBs as suggested from previous experimental studies. [ABSTRACT FROM AUTHOR]

Abstract: From June 1989 through to November 1998, 121 children with newly diagnosed T-cell lymphoblastic lymphoma (T-LBL) were included in the EORTC 58881 trial conducted by the Children’s Leukaemia Group. The therapy regimen was based on a Berlin-Frankfurt-Munster protocol, for a total duration of 24 months. Cranial irradiation, prophylactic cranial and local, was omitted, even for patients with central nervous involvement at diagnosis. In total, 119 patients were evaluable. The median follow-up was 6.7 years. The overall event-free survival (EFS) rate at 6 years was 77.5% (standard error (SE)=4%). Median time of relapse was 1 year after complete remission (range 0.2–5.9 years). Only two (1.8%) patients had an isolated central nervous system relapse. For patients with complete response (n =16) to the 7-day prephase, the EFS rate at 6 years was 100% versus 14% (P <0.001) for patients with no response (n =7). Overall survival rate at 6 years was 86% (SE=3%). An intensive acute lymphoblastic leukaemia type chemotherapy regimen without irradiation leads to a high cure and survival rate in childhood T-LBL without an increased CNS recurrence. This suggests that prophylactic cranial irradiation can safely be omitted. Response to the prephase appeared to be a strong prognostic factor for EFS. [Copyright &y& Elsevier]

To distinguish the similarities or differences between T-cell acute lymphoblastic leukaemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL), we retrospectively analyzed the clinical, immunophenotypic, cytogenetic, and molecular characteristics in 37 children diagnosed between December 1990 and December 2003. Comparative Expressed Sequence Hybridisation (CESH) was used to determine gene expressing profile in both diseases. Twenty two patients suffered from T-ALL and 15 patients were diagnosed as T-LBL. Immunophenotyping demonstrated a more immature phenotype in T-ALL and a more mature phenotype in T-LBL. Cytogenetic and molecular genetic aberrations were found in 82% of T-ALL compared with 73% of T-LBL. By CESH gene expression profiling, the investigated cases were segregated into two groups that largely corresponded with T-ALL and T-LBL. The clinical presentation and cytogenetic characteristics are largely similar for T-ALL and T-LBL supporting the concept that both represent a spectrum of one single disease. The differences that were found between both neoplasms, in particular in their phenotype and in their expression profile may suggest that most T-ALL derive from a T-cell progenitor of the bone marrow, while thymocytes represent the normal counterpart of T-LBL. [ABSTRACT FROM AUTHOR]

The aim of this study was to describe the acute effects of anthracyclines on left ventricular systolic and diastolic function using different echocardiographic modalities. Thirteen children scheduled to receive anthracyclines were prospectively studied. They underwent complete 2-dimensional and Doppler echocardiographic evaluations, including tissue Doppler imaging, before the first dose and <2 hours after each of the first 3 doses of anthracyclines (dose range 30 to 75 mg/m2). After the first dose, increased end-diastolic wall thickness, decreased wall thickening, and a prolonged myocardial performance index were noted. Parameters of diastolic function changed significantly, with a lower mitral E wave, a decreased E/A ratio, and prolonged isovolumic relaxation time. Also, reduced longitudinal early diastolic myocardial velocity and myocardial velocity acceleration during isovolumic contraction as well as reduced peak longitudinal and radial systolic strain rate and strain were noted. All these parameters remained significantly lower after subsequent doses. After the second dose, significant changes in the shortening fraction and the ejection fraction compared with baseline became apparent. After the third dose, further deterioration in radial peak systolic strain was seen. In conclusion, low to moderate doses of anthracyclines acutely induce cardiac diastolic and systolic dysfunction. [Copyright &y& Elsevier]

Ataxia-telangiectasia (AT) is an autosomal recessive syndrome of combined immunodeficiency. Hallmarks of the disease comprise progressive cerebellar ataxia, oculocutaneous telangiectasia, cancer susceptibility and variable humoral and cellular immunodeficiency. We describe a patient with AT presenting with autoimmune haemolytic anaemia, neutropenia, hepatosplenomegaly, lymphadenopathy and hyper-IgM at the age of 6 months. At the age of 26 months she developed persistent fever, progressive lymphadenopathy and pulmonary nodular infiltrates, which were responsive to steroid therapy. [ABSTRACT FROM AUTHOR]

We report on a patient with a history of Ewing sarcoma who underwent surgery and subsequent adjuvant chemotherapy and radiotherapy. He developed low-back pain 6 months after the end of the radiotherapy and during consolidation chemotherapy. Magnetic resonance imaging showed evidence of myositis corresponding to the 'radiation-recall phenomenon', an inflammatory reaction of irradiated tissue. [ABSTRACT FROM AUTHOR]

Background: Although continuity of care in paediatric palliative care (PPC) is considered to be an essential element of quality of care, it's implementation is challenging. In Belgium, five paediatric liaison teams (PLTs) deliver palliative care. A Royal Decree issued in 2010 provides the legal framework that defines the PLTs' missions, as ensuring continuity of curative and palliative care between the hospital and home for children diagnosed with life-limiting conditions. This national study describes how PLTs ensure continuity of care by describing their activities and the characteristics of the children they cared for from 2010 to 2014. Methods: Thematic analysis of open-ended questions was performed and descriptive statistics of aggregated data issued from annual reports, collected by the Belgian Ministry of Public Health through the Cancer Plan was used. A review panel of PLT members discussed the results and contributed to their interpretation. Results: Between 2010 and 2014, 3607 children and young adults (0–21 years) were cared for by the 5 Belgian PLTs (mean of 721/per year). Of these children, 50% were diagnosed with an oncological disease, 27% with a neurological or metabolic disease. Four hundred and twenty eight (428) children had died. For 51% of them, death took place at home. PLT activities include coordination; communication; curative and palliative care; education; research and fundraising. Different perceptions of what constitutes a palliative stage, heterogeneity in reporting diagnosis and the current lack of specific valid indicators to report PPC activities were found. Conclusion: PLTs are offering highly individualised, flexible and integrated care from diagnosis to bereavement in all care settings. Improvements in data registration and implementation of outcome measures are foreseen. [ABSTRACT FROM AUTHOR]

Vitamin A intoxication is a rare cause of liver disease, but the risk increases in patients with underlying liver dysfunction. We present a patient with Shwachman-Diamond Syndrome who developed liver fibrosis, portal hypertension and very severe hepatopulmonary syndrome as a consequence of chronic vitamin A intoxication. She underwent successful liver transplantation with complete resolution of the pulmonary shunting. [ABSTRACT FROM AUTHOR]

The article presents a case study of a newborn female patient who was born via a complicated vaginal delivery at home. A discussion of persistent pallor seen in the patient which resulted in her under going diagnostic testing that revealed the presence of acute myeloid leukemia is presented. The patient's death, which occurred on the 16th day of her life, is discussed.

A letter to the editor is presented concerning a case of pancytopenia and bone marrow BK-virus (BKV) infection in a 17-year-old male with polyomavirus nephropathy and a transplanted cadaveric kidney.

Background: Olmsted syndrome is a rare congenital skin disorder presenting with periorifical hyperkeratotic lesions and mutilating palmoplantar keratoderma, which is often associated with infections of the keratotic area. A recent study identified de novo mutations causing constitutive activation of TRPV3 as a cause of the keratotic manifestations of Olmsted syndrome.Methods: Genetic, clinical and immunological profiling was performed on a case study patient with the clinical diagnosis of Olmsted syndrome.Results: The patient was found to harbour a previously undescribed 1718G-C transversion in TRPV3, causing a G573A point mutation. In depth clinical and immunological analysis found multiple indicators of immune dysregulation, including frequent dermal infections, inflammatory infiltrate in the affected skin, hyper IgE production and elevated follicular T cells and eosinophils in the peripheral blood.Conclusions: These results provide the first comprehensive assessment of the immunological features of Olmsted syndrome. The systemic phenotype of hyper IgE and persistent eosinophilia suggest a primary or secondary role of immunological processes in the pathogenesis of Olmsted syndrome, and have important clinical consequences with regard to the treatment of Olmsted syndrome patients. [ABSTRACT FROM AUTHOR]