Haemangioma of Infancy: Two Case Reports with an Overdose of Propranolol

An 8-week-old infant was treated with oral propranolol for a haemangioma of infancy. The standard dose (according to protocol) is 2 mg/kg/day but, because of a mistake by the pharmacist, the child was treated with 8 mg/kg/day without any side effects (pulse, blood pressure and glucose stayed normal)

Parenting children with a cleft lip with or without palate or a visible infantile hemangioma: A cross-sectional study of distress and parenting stress

Objective: Parents of children with a medical condition and a visible difference can experience challenging situations. We evaluated distress and parenting stress in parents of children with a cleft lip with or without cleft palate (CL +/- P) or a visible infantile hemangioma (IH). Setting: This cross-sectional study took place in an academic medical hospital in Rotterdam, the Netherlands. Participants: Three-hundred nine parents (mean age = 40.30, 56.00% mothers) of children with CL +/- P and 91 parents (mean age = 36.40, 58.24% mothers) of children with IH. Main Outcome Measures: The Dutch version of the Parenting Stress Index - Short Form and the subscales Anxiety, Depression, and Hostility of the Symptom Checklist - 90. Results: One sample t tests and mixed linear modeling were used. On average, parents of children with CL +/- P and of children with IH showed significantly lower parenting stress compared to normative data. Anxiety was significantly lower in parents of children with CL +/- P than that in the norm group. Visibility of the condition was not related to distress or parenting stress. Child behavioral problems were positively related to parenting stress, depression, and hostility. Conclusions: Parents of children with CL +/- P and IH report less distress and parenting stress compared to the norm. On average, these parents seem well adjusted. A practical implication is to monitor parents of children with behavioral problems.Stress and Psychopatholog

Mesenchymal stromal cells and vascular morphogenesis: gene expression profiles and promoting pathways

Objective: Hematopoietic cells and mesenchymal stromal cells are closely related to endothelial cells in theembryological cell differentiation lineages. To study the pathobiology of vascular immunology and microenvironmentin vascular morphogenesis, we analyzed the genetic factors known to be involved in vascular anomalies in humansand mice in the expression data from the Immunological Genome Project (ImmGen).Methods: We mined the Pictures of Standard Syndromes of Undiagnosed Malformations and NCBI OnlineMendelian Inheritance in Man databases to construct a gene list related to vasculature. We studied the expressionsignatures of these genes in the ImmGen database. Hierarchical clustering analyses were performed using Partek®Genomics Suite 6.6. Next, the acquired clusters were separately investigated within Ingenuity Pathway Analysis(IPA). Based on these results we performed a Principal Component Analysis (PCA) with pericyte samples from aseparate database to investigate the relation with pericytes.Results: Our database queries resulted in a gene list of 438 genes related to vasculature, of which 384 could bestudied within the ImmGen data set. Through hierarchical clustering we identified five distinct clusters of whichone was specific for expression in mesenchymal cell lines. Next, using IPA we found various pathways related topericyte functions. A subsequent PCA with pericyte samples showed a close resemblance to specific stromal cells ofmesenchymal origin indicating shared expression profiles for vascular genes between pericytes and these cell types.These results indicate that the processes of Epithelial-Mesenchymal-Transition and or Endothelial-MesenchymalTransition underly the interaction between epithelial/endothelial cells and mesenchymal stromal cells in vascularmorphogenesis.Conclusion: In this data analysis study, we performed data fusion from various sources that may aid futuremechanistic and therapeutic studies in study design and cell type selection as well as provide a potential strategyto find therapeutic targets based on the specific pathological molecular mechanisms related to vascular anomalies

Mesenchymal stromal cells and vascular morphogenesis: gene expression profiles and promoting pathways

Objective: Hematopoietic cells and mesenchymal stromal cells are closely related to endothelial cells in theembryological cell differentiation lineages. To study the pathobiology of vascular immunology and microenvironmentin vascular morphogenesis, we analyzed the genetic factors known to be involved in vascular anomalies in humansand mice in the expression data from the Immunological Genome Project (ImmGen).Methods: We mined the Pictures of Standard Syndromes of Undiagnosed Malformations and NCBI OnlineMendelian Inheritance in Man databases to construct a gene list related to vasculature. We studied the expressionsignatures of these genes in the ImmGen database. Hierarchical clustering analyses were performed using Partek®Genomics Suite 6.6. Next, the acquired clusters were separately investigated within Ingenuity Pathway Analysis(IPA). Based on these results we performed a Principal Component Analysis (PCA) with pericyte samples from aseparate database to investigate the relation with pericytes.Results: Our database queries resulted in a gene list of 438 genes related to vasculature, of which 384 could bestudied within the ImmGen data set. Through hierarchical clustering we identified five distinct clusters of whichone was specific for expression in mesenchymal cell lines. Next, using IPA we found various pathways related topericyte functions. A subsequent PCA with pericyte samples showed a close resemblance to specific stromal cells ofmesenchymal origin indicating shared expression profiles for vascular genes between pericytes and these cell types.These results indicate that the processes of Epithelial-Mesenchymal-Transition and or Endothelial-MesenchymalTransition underly the interaction between epithelial/endothelial cells and mesenchymal stromal cells in vascularmorphogenesis.Conclusion: In this data analysis study, we performed data fusion from various sources that may aid futuremechanistic and therapeutic studies in study design and cell type selection as well as provide a potential strategyto find therapeutic targets based on the specific pathological molecular mechanisms related to vascular anomalies

Emotional and behavioral problems in children with a cleft lip with or without palate or an Infantile Hemangioma

Objective: Life can be challenging for children with a visible difference due to a medical condition, and they might be at risk for emotional and behavioral problems. This study examines emotional and behavioral problems in children with a cleft lip with or without palate (CL +/- P) or an infantile hemangioma (IH) in relation to the visibility of the condition, the presence of additional condition-related problems, and parental affect. Setting: This cross-sectional study took place in an academic medical hospital in the Erasmus MC Sophia Children's Hospital, the Netherlands. Participants: A total of 309 parents (mean age = 40.34, 44.00% male) of 182 children with CL +/- P and 48 parents (mean age = 39.21, 37.50% male) of 33 children with an IH completed questionnaires. Children were 1.5 to 12 years old. Results: Parents reported fewer child emotional and behavioral problems compared to normative data. Problems reported were mainly related to learning difficulties and parent gender, while visibility of the condition had no significant influence. Parental negative affect was related to child internalizing problems. Parental positive affect was not related to any of the outcome measures. Conclusions: Parents reported fewer problems for their children compared to normative data. This is inconsistent with previous research, showing similar or worse scores for these children compared to peers. Our findings may be explained by a protective parenting style, a response shift in parents, or problems developing at a later point in life.Stress and Psychopatholog

Infantile fibrosarcoma with an EGFR kinase domain duplication: underlining a close relationship with congenital mesoblastic nephroma and highlighting a similar morphological spectrum

Infantile fibrosarcoma (IFS) and congenital mesoblastic nephroma (CMN) are locally aggressive tumors primarily occurring in infants. Both IFS and the cellular subtype of CMN show overlapping morphological features and an ETV6-NTRK3 fusion, suggesting a close relationship. An activating alteration of EGFR, based on an EGFR kinase domain duplication (KDD), occurs in a subset of CMNs lacking an NTRK3 rearrangement, especially in the classic and mixed type. So far no EGFR-KDDs have been detected in IFS.We describe four pediatric tumors at the extremities (leg, n = 2; foot and arm n = 1) with histological features of IFS/CMN. Two cases showed classic IFS morphology while two were similar to classic/mixed type CMN. In all cases, an EGFR-KDD was identified without detection of a fusion gene. There were no abnormalities of the kidneys in any of the patients.This is the first description of IFS with an EGFR-KDD as driver mutation, supporting that IFS and CMN are similar lesions with the same morphological and genetic spectrum. Pathologists should be aware of the more fibrous variant of IFS, similar to classic/mixed type CMN. Molecular analyses are crucial to treat these lesions adequately, especially with regard to the administration of tyrosine kinase inhibitors.Orthopaedics, Trauma Surgery and Rehabilitatio