Paediatric endoscopic endonasal middle skull base reconstruction: retrospective analysis of 78 patients treated in a single tertiary care paediatric center.

Introduction: Skull base pathologies in the paediatric population are rare and require treatment by multiple qualified specialists. The endoscopic endonasal approach has revolutionized surgical treatment because it is less invasive than existing treatments.The goal of this study was to retrospectively review our experience with the reconstruction of paediatric skull middle base defects and associated complications.

Endoscopic Endonasal Treatment of Intra-Axial Ventral Brainstem Cavernomas: Case Experience and Literature Review.

Introduction: Cavernous malformations of the ventral brainstem are a challenging disease to treat. From an anatomical perspective, the best surgical options are endoscopic endonasal approaches. The first reports of their usage for this purpose date back to 2012.

Orphan Drug Use in Patients With Rare Diseases: A Population-Based Cohort Study.

Orphan drugs are used for the diagnosis, prevention and treatment of rare diseases that, in the European Union, are defined as disorders affecting no more than 5 persons in 10,000. So far, a total of around 800 orphan medicinal products have been approved by the European Medicines Agency, however the utilization profile of orphan drugs has yet to be explored. This study aimed at assessing the utilization profile of orphan drugs authorized for marketing by the Italian Medicines Agency using population-based data.

Moving from nature to nurture: a systematic review and meta-analysis of environmental factors associated with juvenile idiopathic arthritis.

Objectives: JIA is the most common paediatric rheumatic disease, thought to be influenced by both genetics and the environment. Identifying environmental factors associated with disease risk will improve knowledge of disease mechanism and ultimately benefit patients. This review aimed to collate and synthesize the current evidence of environmental factors associated with JIA.

Movement Disorders in Children with a Mitochondrial Disease: A Cross-Sectional Survey from the Nationwide Italian Collaborative Network of Mitochondrial Diseases.

Movement disorders are increasingly being recognized as a manifestation of childhood-onset mitochondrial diseases (MDs). However, the spectrum and characteristics of these conditions have not been studied in detail in the context of a well-defined cohort of patients. We retrospectively explored a cohort of individuals with childhood-onset MDs querying the Nationwide Italian Collaborative Network of Mitochondrial Diseases database.

Chiari 1 malformation and exome sequencing in 51 trios: the emerging role of rare missense variants in chromatin-remodeling genes.

Type 1 Chiari malformation (C1M) is characterized by cerebellar tonsillar herniation of 3-5 mm or more, the frequency of which is presumably much higher than one in 1000 births, as previously believed. Its etiology remains undefined, although a genetic basis is strongly supported by C1M presence in numerous genetic syndromes associated with different genes. Whole-exome sequencing (WES) in 51 between isolated and syndromic pediatric cases and their relatives was performed after confirmation of the defect by brain magnetic resonance image (MRI).

Stem cell transplantation for children with hemophagocytic lymphohistiocytosis: results from the HLH-2004 study.

We report the largest prospective study thus far on hematopoietic stem cell transplantation (HSCT) in hemophagocytic lymphohistiocytosis (HLH), a life-threatening hyperinflammatory syndrome comprising familial/genetic HLH (FHL) and secondary HLH. Although all patients with HLH typically need intensive anti-inflammatory therapy, patients with FHL also need HSCT to be cured. In the international HLH-2004 study, 187 children aged <18 years fulfilling the study inclusion criteria (5 of 8 diagnostic criteria, affected sibling, or molecular diagnosis in FHL-causative genes) underwent 209 transplants (2004-2012), defined as indicated in patients with familial/genetic, relapsing, or severe/persistent disease.

Comparison of three different ELISAs for the detection of recombinant, native and plasma IL-17A.

Plasma IL-17A detection in Langerhans Cell Histiocytosis (LCH) is currently a source of debate. Indeed, 500-P07G (PeproTech) and 41802 (R&D Systems) anti-IL-17A antibodies have been suspected to recognize nonspecific proteins. To resolve this discrepancy, we set up two new ELISAs by using 41802 or neutralizing eBio64CAP17 (eBioscience) capture monoclonal antibodies that we compared to the commercial PeproTech ELISA kit.

Use of Eltrombopag in Children With Chronic Immune Thrombocytopenia (ITP): A Real Life Retrospective Multicenter Experience of the Italian Association of Pediatric Hematology and Oncology (AIEOP).

The thrombopoietin receptor agonist eltrombopag has been shown to be safe and effective for children with chronic immune thrombocytopenia (ITP). The aim of the present study was to characterize eltrombopag use in current clinical practice. This is a retrospective multicenter study conducted in 17 centers affiliated to the Italian Association of Pediatric Hematology and Oncology (AIEOP).

High levels of plasma interleukin-17A are associated with severe neurological sequelae in Langerhans cell histiocytosis.

Objective: Langerhans cell histiocytosis (LCH) is a granulomatous inflammatory myeloid neoplasia associated with a cytokine storm in both serum and lesions. Increased levels of plasma interleukin-17A (IL-17A) in LCH patients have been reported, but this finding was not confirmed in all studies. Neurodegeneration is a devastating complication of LCH (ND-LCH).

Early neurodevelopmental characterization in children with cobalamin C/defect.

Cobalamin C (cblC) defect is the most common inherited disorder of cobalamin metabolism. Developmental delay, behavioral problems, and maculopathy are common, but they have not been systematically investigated. The aim of this study was to define early neurodevelopment in cblC patients and the possible contribution of different factors, such as mode of diagnosis, age at diagnosis, presence of brain lesions and epilepsy.

Recommendations for the Use of Etoposide-Based Therapy and Bone Marrow Transplantation for the Treatment of HLH: Consensus Statements by the HLH Steering Committee of the Histiocyte Society.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome requiring aggressive immunosuppressive therapy. Following 2 large international studies mainly targeting pediatric patients with familial disease and patients without underlying chronic or malignant disease, the HLH-94 protocol is recommended as the standard of care when using etoposide-based therapy by the Histiocyte Society. However, in clinical practice, etoposide-based therapy has been widely used beyond the study inclusion criteria, including older patients and patients with underlying diseases (secondary HLH).

Long-term results of the AIEOP MH'96 childhood Hodgkin's lymphoma trial and focus on significance of response to chemotherapy and its implication in low risk patients to avoid radiotherapy.

Identify a subset of early-stage HL children (GR1) curable with limited chemotherapy+/-radiotherapy; improve outcome of intermediate (GR2) and high-risk (GR3) patients; establish impact of response to chemotherapy evaluated with conventional imaging (CI). One hundred and sixty GR1-patients received 3ABVD + involved-field (IF) low-dose (LD) (20 Gy) irradiation if mediastinal mass or partial response (PR) after chemotherapy. Eighty-five GR2- and 315 GR3-patients received 4 and 6 COPP/ABV + IFRT, respectively.

Diffusion Tensor Imaging to Map Brain Microstructural Changes in CADASIL.

Background And Purpose: Diffusion tensor imaging (DTI) is sensitive to brain microstructural changes. The aims of this DTI study were to map voxelwise the spatial distribution of brain microstructural changes in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and to investigate any correlation between DTI-derived indices and extension of T2 hyperintensity.

Methods: Eighteen patients with CADASIL and 18 age-, sex-, and education-level-matched healthy controls underwent magnetic resonance imaging at 3 T.

Diffuse Brain Hypoperfusion in Advanced Leukoencephalopathy with Calcifications and Cysts.

Leukoencephalopathy with calcifications and cysts (LCC) is an uncommon condition of unknown etiology occurring in children and adults. Pathological findings include obliterative hyalinosis of the small vessels, myelin loss, intense gliosis, Rosenthal fiber formation, microcalcifications, and hemosiderin deposits. Herein we report a 55-year-old man with LCC documented 10 years ago, in whom we examined brain perfusion by pseudocontinuous arterial spin labeling technique.

Risk of seizures in children receiving busulphan-containing regimens for stem cell transplantation.

Busulphan (BU) is associated with neurotoxicity and risk of seizures. Hence, seizure prophylaxis is routinely utilized during BU administration for stem cell transplantation (SCT). We collected data on the incidence of seizures among children undergoing SCT in Italy.

Children monosensitized to pine nuts have similar patterns of sensitization.

Background: Several cases of pine nut allergies and anaphylaxis have been reported in the literature, but only few pine nut allergens have been characterized. The aim of this research is to identify through immunoelectrophoretic techniques the major pine nut allergens in a group of children monosensitized to pine nuts.

Methods: We studied five children with pine nut allergies and no other sensitization to food except to pine nuts, confirmed by in vivo (prick test, prick-to-prick) and in vitro tests (specific IgE determinations [CAP-FEIA]).

Familial hemophagocytic lymphohistiocytosis may present during adulthood: clinical and genetic features of a small series.

Familial Hemophagocytic lymphohistiocytosis (FHL) is a rare immune deficiency with defective cytotoxic function. The age at onset is usually young and the natural course is rapidly fatal if untreated. A later onset of the disease has been sporadically reported even in adolescents and adults.

CD4+CD25+Foxp3+ T regulatory cells are not involved in oral desensitization.

Oral tolerance has been related to generation of T regulatory cells (Treg) or clonal anergy/deletion, respectively by administering low and high doses of fed antigens. CD4+CD25+ regulatory T cell clones can be induced by the antigen in Peyers patches of animal models. We selected ten subjects (mean age: 89.