Effects of Depilatory Cream Formulation and Contact Time on Mouse Skin.

Depilatory creams are widely used in research to remove hair in preparation for surgery, imaging, and other procedures. However, few studies have evaluated the effects of these creams on mouse skin. We sought to determine the cutaneous effects of 2 different depilatory formulations of a widely used brand as related to the duration of exposure.

Dabigatran in the treatment and secondary prophylaxis of venous thromboembolism in children with thrombophilia.

In the phase 2b/3 DIVERSITY trial, 3 months treatment with dabigatran was noninferior to standard of care (SOC) for acute venous thromboembolism (VTE) in children. In a single-arm, phase 3, secondary VTE prevention study, up to 12 months dabigatran use was associated with favorable safety. Dabigatran is approved by the European Medicines Agency and US Food and Drug Administration for pediatric indications.

Evaluation of Nutritional Gel Supplementation in C57BL/6J Mice Infected with Mouse-Adapted Influenza A/PR/8/34 Virus.

Mice are a common animal model for the study of influenza virus A (IAV). IAV infection causes weight loss due to anorexia and dehydration, which can result in early removal of mice from a study when they reach a humane endpoint. To reduce the number of mice prematurely removed from an experiment, we assessed nutritional gel (NG) supplementation as a support strategy for mice infected with mouse-adapted Influenza A/Puerto Rico/8/34 (A/PR/8/34; H1N1) virus.

Dual BRD4 and AURKA Inhibition Is Synergistic against MYCN-Amplified and Nonamplified Neuroblastoma.

A majority of cases of high-risk neuroblastoma, an embryonal childhood cancer, are driven by MYC or MYCN-driven oncogenic signaling. While considered to be directly "undruggable" therapeutically, MYC and MYCN can be repressed transcriptionally by inhibition of Bromodomain-containing protein 4 (BRD4) or destabilized posttranslationally by inhibition of Aurora Kinase A (AURKA). Preclinical and early-phase clinical studies of BRD4 and AURKA inhibitors, however, show limited efficacy against neuroblastoma when used alone.

Danger-Associated Molecular Patterns Derived From the Extracellular Matrix Provide Temporal Control of Innate Immunity.

It is evident that components of the extracellular matrix (ECM) act as danger-associated molecular patterns (DAMPs) through direct interactions with pattern recognition receptors (PRRs) including Toll-like receptors (TLRs) and inflammasomes. Through these interactions, ECM-derived DAMPs autonomously trigger sterile inflammation or prolong pathogen-induced responses through the production of proinflammatory mediators and the recruitment of leukocytes to sites of injury and infection. Recent research, however, suggests that ECM-derived DAMPs are additionally involved in the resolution and fine-tuning of inflammation by orchestrating the production of anti-inflammatory mediators that are required for the resolution of tissue inflammation and the transition to acquired immunity.

Pilot Study of Adding Vincristine, Topotecan, and Cyclophosphamide to Interval-Compressed Chemotherapy in Newly Diagnosed Patients With Localized Ewing Sarcoma: A Report From the Children's Oncology Group.

Background: The combination of topotecan and cyclophosphamide is active in relapsed Ewing sarcoma family of tumors (ESFT). The feasibility of adding these agents combined with vincristine (vincristine-topotecan-cyclophosphamide [VTc]) to standard five-drug chemotherapy with vincristine-doxorubicin-cyclophosphamide (VDC) and ifosfamide-etoposide (IE) administered in an interval-compressed (2-week instead of 3-week intervals) schedule was investigated.

Procedure: Newly diagnosed patients with localized ESFT < 31 years, with good performance status and adequate organ function were eligible.

Identification of Discrete Prognostic Groups in Ewing Sarcoma.

Background: Although multiple prognostic variables have been proposed for Ewing sarcoma (EWS), little work has been done to further categorize these variables into prognostic groups for risk classification.

Procedure: We derived initial prognostic groups from 2,124 patients with EWS in the SEER database. We constructed a multivariable recursive partitioning model of overall survival using the following covariates: age; stage; race/ethnicity; sex; axial primary; pelvic primary; and bone or soft tissue primary.

Regulatory barriers to clinical trial enrollment of adolescent and young adult oncology patients.

Adolescent and young adult (AYA) patients with cancer may face unique challenges if they and their families wish to participate in clinical oncology trials. Regulatory guidelines and funding requirements put in place to protect patients may actually raise barriers to enrollment in clinical trials. Hospital age guidelines may need to be readdressed to better suit the needs of AYA patients.

Children's Oncology Group's 2013 blueprint for research: adolescent and young adult oncology.

The discipline of Adolescent and Young Adult (AYA) Oncology addresses compelling medical and psychosocial needs of AYA patients across the spectrum of cancer survivorship. To be successful, extraordinary collaboration involving multiple scientific disciplines and specialties is required. While AYA Oncology is international in scope, recent AYA-focused studies conducted in the Children's Oncology Group (COG) have documented survival disparities, toxicity differences, and biological insights that provide the basis for new COG trials and initiatives for this population.

A pilot study of low-dose anti-angiogenic chemotherapy in combination with standard multiagent chemotherapy for patients with newly diagnosed metastatic Ewing sarcoma family of tumors: A Children's Oncology Group (COG) Phase II study NCT00061893.

Background: The aims of this study were to determine the feasibility of the combination of low dose, anti-angiogenic chemotherapy with standard therapy for patients with metastatic Ewing sarcoma (ES), and to obtain preliminary outcome data.

Procedures: Patients with metastatic ES were eligible. Therapy consisted of alternating cycles of ifosfamide-etoposide, and vincristine, doxorubicin, cyclophosphamide.

Increasing diversity in pediatric hematology/oncology.

Background: Diversity is necessary for the survival and success of both biological and social systems including societies. There is a lack of diversity, particularly the proportion of women and minorities in leadership positions, within medicine [Leadley. AAMC 2009.

Localized purpura associated with lamotrigine.

Antiepileptic drug hypersensitivity syndrome consists of fever, rash, and internal organ involvement and usually occurs within the first 2 months of initiation of therapy. This report describes a 13-year-old female with a right frontal high-grade glioma and complex partial seizures who developed localized purpura after 23 months of lamotrigine monotherapy. This case study is the second report of localized purpura after prolonged lamotrigine treatment suggesting this may be an atypical lamotrigine-induced drug reaction.

Toxicity and efficacy of intensive chemotherapy for children with acute lymphoblastic leukemia (ALL) after first bone marrow or extramedullary relapse.

Background: Approximately 25% of children newly diagnosed with acute lymphoblastic leukemia (ALL) will eventually experience leukemic relapse, with bone marrow being the most common site of recurrence. The ability to achieve a durable second remission is complicated by toxicity and resistant disease. We report a novel combination of chemotherapy for relapsed pediatric ALL.

Asparaginase pharmacokinetics after intensive polyethylene glycol-conjugated L-asparaginase therapy for children with relapsed acute lymphoblastic leukemia.

Purpose: Asparaginase therapy is an important component in the treatment of children with acute lymphoblastic leukemia. Polyethylene glycol-conjugated asparaginase (PEG-ASNase) has significant pharmacological advantages over native Escherichia coli asparaginase. We investigated the pharmacokinetics of PEG-ASNase, presence of antibodies to PEG-ASNase, and concentrations of asparagine in serum and cerebrospinal fluid (CSF) in combination chemotherapy for relapsed pediatric acute lymphoblastic leukemia.

Intensive induction chemotherapy and delayed irradiation in the management of parameningeal rhabdomyosarcoma.

Purpose: To evaluate local control, event-free survival, and overall survival for patients with parameningeal (PM) rhabdomyosarcoma (RMS) treated with intensive chemotherapy and delayed irradiation.

Patients And Methods: Thirteen consecutive patients with PM RMS were treated with an institutional protocol from 1992 to 1998 at the University of Washington/Children's Hospital and Regional Medical Center and Deaconess Medical Center. Patients received intensive chemotherapy consisting of vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide prior to radiotherapy.

Peripheral blood stem cell support reduces the toxicity of intensive chemotherapy for children and adolescents with metastatic sarcomas.

Background: To increase the dose intensity (DI) of chemotherapy for pediatric patients with metastatic sarcomas, including the Ewing sarcoma family of tumors (ESFT) and rhabdomyosarcoma (RMS), the authors tested the feasibility of an intensive regimen supported by granulocyte-colony stimulating factor (G-CSF) and peripheral blood stem cells (PBSC).

Methods: Twenty-three children and adolescents with metastatic sarcomas received vincristine, doxorubicin, cyclophosphamide, ifosfamide, sodium mercaptoethanesulfonate (mensa), and etoposide (VACIME) chemotherapy, consisting of 8 courses of vincristine 2 mg/m(2) on Day 0, doxorubicin 37.5 mg/m(2) per day on Days 0-1, cyclophosphamide 360 mg/m(2) per day on Days 0-4, ifosfamide 1800 mg/m(2) per day on Days 0-4, mesna 2400 mg/m(2) per day, and etoposide 100 mg/m(2) per day on Days 0-4.

No excess of early onset cancer in family members of Wilms tumor patients.

Background: Wilms tumor is one of the few pediatric cancers with well-defined familial and genetic components. The authors assessed the risk of early-onset cancers in first- and second-degree relatives of patients enrolled by the National Wilms Tumor Study Group.

Methods: Using a stratified sampling scheme that targeted 530 families of patients who were believed a priori to have a genetic contribution to their disease, the authors conducted interviews regarding cancer occurrence in 4258 family members from 296 families of patients with Wilms tumor.

Successful dose-intensive treatment of desmoplastic small round cell tumor in three children.

Desmoplastic small round cell tumor (DSRCT) is a rare soft tissue tumor of primitive origin occurring primarily in children and young adults. Based on published reports in the literature, the response to conventional chemotherapy is poor. We report three pediatric patients successfully treated with dose-intensive, multimodal therapy.

Very intensive, short-term chemotherapy for children and adolescents with metastatic sarcomas.

Background: To improve the prognosis for pediatric patients with metastatic sarcomas, including the Ewing sarcoma family of tumors (ESFT), rhabdomyosarcoma (RMS), and undifferentiated sarcoma (UDS), we tested the feasibility of a brief, intensive regimen of chemotherapy that maximizes dose intensity.

Procedure: Twenty-four children and adolescents with metastatic sarcomas received VACIME chemotherapy, consisting of eight courses of vincristine 2 mg/m(2) on day 0; doxorubicin 20 mg/m(2)/day on days 0-3; cyclophosphamide 360 mg/m(2)/day on days 0-4; ifosfamide 1,800 mg/m(2)/day on days 0-4; mesna 2,400 mg/m(2)/day; and etoposide 100 mg/m(2)/day on days 0-4. Doxorubicin was omitted in courses 7 and 8.

RT-PCR evaluation of peripheral blood, bone marrow and peripheral blood stem cells in children and adolescents undergoing VACIME chemotherapy for Ewing's sarcoma and alveolar rhabdomyosarcoma.

Peripheral blood stem cell support allows dose intensification of multiple cycle chemotherapy for metastatic tumors, including pediatric sarcomas. The VACIME protocol (vincristine, adriamycin, cyclophosphamide, ifosfamide, mesna and etoposide) utilizes peripheral blood stem cells (PBSC) collected following the treatment cycle as support for subsequent dose- and time-intensive chemotherapy. A critical assumption is that PBSC collected in this manner will be purged of residual tumor cells in vivo.

Elevated zinc protoporphyrin associated with thalassemia trait and hemoglobin E.

Objective: Increased zinc protoporphyrin/heme (ZPP/H) ratio has been used in pediatrics to screen for iron deficiency and lead poisoning. This study was conducted to determine whether common hereditary hemoglobin disorders (alpha- and beta-thalassemia traits, hemoglobin E) found in U.S.

Relationship between epidemiologic risk factors and clinicopathologic findings in the sudden infant death syndrome.

The risk of sudden infant death syndrome (SIDS) is said to be enhanced by factors such as prematurity, low birth weight, and perinatal distress. The significance of risk factors for SIDS research was questioned because the majority of SIDS victims seem to lack them. Therefore, postmortem records of 1144 infants who died suddenly and unexpectedly in King County, Washington, over a 25-year period were studied.