Ewing Sarcoma of the 9th Rib Subsequent to Pediatric Leukemia: A Case Series.

Ewing sarcoma is an aggressive malignancy of bone and soft tissue that accounts for ∼2% of cases of childhood cancer. It has been rarely reported as a secondary neoplasm. Data from the Childhood Cancer Survivor Study has evaluated secondary sarcomas in 5-year survivors of childhood cancer.

IFN-γ signature in the plasma proteome distinguishes pediatric hemophagocytic lymphohistiocytosis from sepsis and SIRS.

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome characterized by pathologic immune activation in which prompt recognition and initiation of immune suppression is essential for survival. Children with HLH have many overlapping clinical features with critically ill children with sepsis and systemic inflammatory response syndrome (SIRS) in whom alternative therapies are indicated. To determine whether plasma biomarkers could differentiate HLH from other inflammatory conditions and to better define a core inflammatory signature of HLH, concentrations of inflammatory plasma proteins were compared in 40 patients with HLH to 47 pediatric patients with severe sepsis or SIRS.

Circulating CD1c+ myeloid dendritic cells are potential precursors to LCH lesion CD1a+CD207+ cells.

Langerhans cell histiocytosis (LCH) is a myeloproliferative disorder that is characterized by the inflammatory lesions with pathogenic CD1a+CD207+ dendritic cells (DCs). BRAFV600E and other somatic activating MAPK gene mutations have been identified in differentiating bone marrow and blood myeloid cells, but the origin of the LCH lesion CD1a+CD207+ DCs and mechanisms of lesion formation remain incompletely defined. To identify candidate LCH CD1a+CD207+ DC precursor populations, gene-expression profiles of LCH lesion CD1a+CD207+ DCs were first compared with established gene signatures from human myeloid cell subpopulations.

Thalidomide, A Rational Agent for Treatment of Multicentric Reticulohistiocytosis.

A patient with Multifocal Reticulohistiocytosis (MRH) of skin and joints failed treatment with etanercept, methotrexate, hydroxychloroquine, prednisone, bisphosphonates and hydroxyzine. Long term treatment with thalidomide led to marked improvement in joint and cutaneous manifestations.

Treatment dilemmas in asymptomatic children with primary hemophagocytic lymphohistiocytosis.

Asymptomatic carriers (ACs) of pathogenic biallelic mutations in causative genes for primary hemophagocytic lymphohistiocytosis (HLH) are at high risk of developing life-threatening HLH, which requires allogeneic hematopoietic stem cell transplantation (HSCT) to be cured. There are no guidelines on the management of these asymptomatic patients. We analyzed the outcomes of pairs of index cases (ICs) and subsequently diagnosed asymptomatic family members carrying the same genetic defect.

CNS Langerhans cell histiocytosis: Common hematopoietic origin for LCH-associated neurodegeneration and mass lesions.

Background: Central nervous system Langerhans cell histiocytosis (CNS-LCH) brain involvement may include mass lesions and/or a neurodegenerative disease (LCH-ND) of unknown etiology. The goal of this study was to define the mechanisms of pathogenesis that drive CNS-LCH.

Methods: Cerebrospinal fluid (CSF) biomarkers including CSF proteins and extracellular BRAFV600E DNA were analyzed in CSF from patients with CNS-LCH lesions compared with patients with brain tumors and other neurodegenerative conditions.

Cost-effectiveness and Improved Parent and Provider Satisfaction With Outpatient Management of Pediatric Oncology Patients, With Low-risk Fever and Neutropenia.

On the basis of significant evidence for safety, the international pediatric fever and neutropenia committee recommends the identification and management of patients with "low-risk fever and neutropenia" (LRFN), outpatient with oral antibiotics, instead of traditional inpatient management. The aim of our study was to compare the cost-per-patient with these 2 strategies, and to evaluate parent and provider satisfaction with the outpatient management of LRFN. Between March 2016 and February 2017, 17 LRFN patients (median absolute neutrophil count, 90/μL) were managed at a single institution, per new guidelines.

Activating MAPK1 (ERK2) mutation in an aggressive case of disseminated juvenile xanthogranuloma.

Juvenile xanthogranuloma (JXG) is a rare histiocytic disorder that is usually benign and self-limiting. We present a case of atypical, aggressive JXG harboring a novel mitogen-activated protein kinase (MAPK) pathway mutation in the MAPK1 gene, which encodes mitogen-activated protein kinase 1 or extracellular signal-regulated 2 (ERK2). Our analysis revealed that the mutation results in constitutive ERK activation that is resistant to BRAF or MEK inhibitors but susceptible to an ERK inhibitor.

Alternative genetic mechanisms of BRAF activation in Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is characterized by inflammatory lesions containing pathologic CD207 dendritic cells with constitutively activated ERK. Mutually exclusive somatic mutations in MAPK pathway genes have been identified in ∼75% of LCH cases, including recurrent BRAF-V600E and MAP2K1 mutations. To elucidate mechanisms of ERK activation in the remaining 25% of patients, we performed whole-exome sequencing (WES, n = 6), targeted BRAF sequencing (n = 19), and/or whole-transcriptome sequencing (RNA-seq, n = 6) on 24 LCH patient samples lacking BRAF-V600E or MAP2K1 mutations.

Adult-Onset Idiopathic Hypertrophic Pyloric Stenosis Associated With Osteoglophonic Dysplasia and HIV: Case Report and Review of Literature.

Adult-onset hypertrophic pyloric stenosis (HPS) is a rare anomaly that can be idiopathic or related to underlying gastric pathology. We describe a case of a 25-year-old man with history of human immunodeficiency virus and osteoglophonic dysplasia who presented with pain and swelling at a gastrostomy site. Computed tomography and upper gastrointestinal barium swallow demonstrated gastric distention and stricture at the distal portion of the gastric antrum.

Langerhans Cell Histiocytosis: Emerging Insights and Clinical Implications.

Langerhans cell histiocytosis is a disorder characterized by lesions that include CD207+ dendritic cells along with an inflammatory infiltrate. Langerhans cell histiocytosis has a highly variable clinical presentation, ranging from a single lesion to potentially fatal disseminated disease. The uncertainty as to whether Langerhans cell histiocytosis is a reactive or a neoplastic disease has resulted in a long-standing debate on this question, and the limited understanding of the pathogenesis of the disease has impeded clinical improvement for patients.

Prevalence of risk of deficiency and inadequacy of 25-hydroxyvitamin D in US children: NHANES 2003-2006.

Aim: To assess prevalence and population estimates of increased risk of 25-hydroxyvitamin D [25(OH)D] deficiency and inadequacy in US children based on the current Institute of Medicine Committee to Review Dietary References Intakes for Vitamin D and Calcium guidelines.

Methods: The analysis was limited to a nationally representative sample of non-institutionalized US children and adolescents aged 6-18 years who participated in the National Health and Nutrition Examination Survey completed in 2003-2006 and had complete data on 25(OH)D measurements (n=2877). The 25(OH)D levels were adjusted for assay drift and prevalence, and population estimates of increased risk of 25(OH)D deficiency (<12 ng/mL), risk of inadequacy (<16 ng/mL), and adequacy (>20 ng/mL) were calculated.

AutoDrug: fully automated macromolecular crystallography workflows for fragment-based drug discovery.

AutoDrug is software based upon the scientific workflow paradigm that integrates the Stanford Synchrotron Radiation Lightsource macromolecular crystallography beamlines and third-party processing software to automate the crystallography steps of the fragment-based drug-discovery process. AutoDrug screens a cassette of fragment-soaked crystals, selects crystals for data collection based on screening results and user-specified criteria and determines optimal data-collection strategies. It then collects and processes diffraction data, performs molecular replacement using provided models and detects electron density that is likely to arise from bound fragments.