A phase 2 pharmacodynamic dose-finding, safety, and efficacy study of dalteparin for pediatric venous thromboembolism treatment in children with and without cancer.

Data from registrational trials of pediatric venous thromboembolism (VTE) treatment are sparse, especially among cancer patients. We conducted a prospective, multicenter, open-label trial (NCT00952380) on dose-finding, safety, and efficacy (measured by 90-day risks of clinically relevant bleeding [CRB] and symptomatic recurrent VTE [srVTE]) of twice-daily subcutaneous dalteparin for acute VTE treatment in patients ≤18 years old. Among 38 patients (cancer, n = 26; noncancer, n = 12), median dalteparin dose requirements per kilogram varied with age but not cancer status. Risks of CRB and srVTE were <4% in cancer and noncancer subgroups. Dalteparin is an important FDA-approved treatment for pediatric VTE, particularly with cancer.

Integration of a Personalized Molecular Targeted Therapy into the Multimodal Treatment of Refractory Childhood Embryonal Tumor with Multilayered Rosettes (ETMR).

Embryonal tumor with multilayered rosettes (ETMR) are rare pediatric brain tumors with increased malignant potential. Despite the advances in multimodal treatment schemes the overall 5-year event free survival rates for ETMR are not favorable. Further, therapeutic regimes are limited to a case by case basis due to the limited amount of literature and guidelines available for treating childhood ETMR. We report one patient with refractory ETMR who was successfully treated by implementing a molecular profiling approach which identified the tyrosine kinase inhibitor dasatinib as a viable therapy. Our results suggest that utilizing this precision medicine approach might prove useful in treating patients with refractory ETMR.

Charge Transfer Models of Zinc and Magnesium in Water.

Quantum mechanical studies point to the importance of polarization and charge transfer (CT) in zinc binding. A new CT force field is used to study these effects in ion-water dimers and in aqueous solution. Quantum mechanics calculations are carried out to determine amounts of CT. Models for zinc and magnesium are parametrized to reproduce solvation structure, hydration free energy, and CT properties. The new models are subjected to energy decomposition, in which the effects of polarization and CT are investigated. The importance of these multibody interactions in the liquid is also considered. We find that, for divalent cations, polarization and charge transfer both strongly affect binding to water. Though polarization increases the internal (self) energy of water and ions, this is more than compensated for by a stronger ion-water interaction energy. The direction of the charge transfer from the water to the cation weakens the ion-water interaction; this increase in energy is counteracted by a decrease in the system energy due to electron delocalization.

An educational module to improve healthcare staffs' attitudes toward sickle cell disease patients.

Sickle cell disease is a genetic blood disorder primarily affecting individuals of African descent. Studies of healthcare providers suggest there is inadequate knowledge about the pathophysiology and clinical presentations of the disease, and misperceptions of patients' behaviors and communication during crisis that have led to inappropriate staff attitudes and thus become major barriers to the delivery of optimal care. In this article, the authors describe the effect of an educational module on improving healthcare staffs' attitudes toward patients with sickle cell disease.

Pediatric phase II trials of poly-ICLC in the management of newly diagnosed and recurrent brain tumors.

Brain tumors are the most common solid tumor diagnosed in childhood that account for significant morbidity and mortality. New therapies are urgently needed; hence, we conducted the first ever prospective open-label phase II trials of the biological response modifier, poly-ICLC, in children with brain tumors. Poly-ICLC is a synthetic double-stranded RNA that has direct antiviral, antineoplastic, and immune adjuvant effects. A total of 47 children representing a variety of brain tumor histopathologic subtypes were treated with poly-ICLC. On the basis of the results of the initial phase II trial, an expanded prospective phase II trial in low-grade glioma (LGG) has been initiated. MRI was used to acquire volume-based measures of tumor response. No dose-limiting toxicities have been observed. In the initial study 3 of 12 subjects with progressive high-grade gliomas (HGGs) responded, and 2 of 4 children with progressive LGG experienced stable disease for 18 to 24 months. In the follow-up LGG phase II study, 2 of 5 LGG patients were stable over 18 months, with 1 stable for 6 months. Overall 5 of 10 LGG patients have responded. On the basis of low toxicity and the promising LGG response, poly-ICLC may be effective for childhood LGG, and the results justify biomarker studies for personalization of poly-ICLC as a single agent or adjuvant.