Response assessment in paediatric low-grade glioma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group.

Paediatric low-grade gliomas (also known as pLGG) are the most common type of CNS tumours in children. In general, paediatric low-grade gliomas show clinical and biological features that are distinct from adult low-grade gliomas, and the developing paediatric brain is more susceptible to toxic late effects of the tumour and its treatment. Therefore, response assessment in children requires additional considerations compared with the adult Response Assessment in Neuro-Oncology criteria.

2019 Pediatric Initiative Network: Progress, Proceedings, and Plans.

Impairment of fertility and sexual/reproductive health are common after oncologic therapy, and are known to have negative impacts on romantic relationships and psychosocial well-being among childhood cancer survivors. The Pediatric Initiative Network (PIN) is an international, multidisciplinary group of providers within the Oncofertility Consortium dedicated to preserving and protecting the fertility of children and adolescents at risk for infertility due to medical conditions or treatments. The PIN and its Best Practices and Research committees meet virtually throughout the year, with one annual in-person meeting.

The biophysics and mechanics of blood from a materials perspective.

Cells actively interact with their microenvironment, constantly sensing and modulating biochemical and biophysical signals. Blood comprises a variety of non-adherent cells that interact with each other and with endothelial and vascular smooth muscle cells of the blood vessel walls. Blood cells are further experiencing a range of external forces by the hemodynamic environment and they also exert forces to remodel their local environment.

Getting a good view: imaging of platelets under flow.

As the anucleate cells responsible for hemostasis and thrombosis, platelets are exposed to a myriad of biophysical and biochemical stimuli within vasculature and heterogeneous blood clots. Highly controlled, reductionist imaging studies have been instrumental in providing a detailed and quantitative understanding of platelet biology and behavior, and have helped elucidate some surprising functions of platelets. In this review, we highlight the tools and approaches that enable visualization of platelets in conjunction with precise control over the local biofluidic and biochemical microenvironment.

Vascularized Microfluidics and the Blood-Endothelium Interface.

The microvasculature is the primary conduit through which the human body transmits oxygen, nutrients, and other biological information to its peripheral tissues. It does this through bidirectional communication between the blood, consisting of plasma and non-adherent cells, and the microvascular endothelium. Current understanding of this blood-endothelium interface has been predominantly derived from a combination of reductionist two-dimensional in vitro models and biologically complex in vivo animal models, both of which recapitulate the human microvasculature to varying but limited degrees.

Microfluidic Approach for Highly Efficient Viral Transduction.

Lentiviral vectors enable gene transfer into target cells, but manufacturing is complex, scale-limited, and costly. Here, we describe the use of microfluidic devices for efficient ex vivo gene transfer. Up to four- to fivefold reductions in viral vector usage and two- to fourfold reductions in transduction times can be obtained by using this method.

Neonatal and pediatric platelet transfusions: current concepts and controversies.

Purpose Of Review: In this review, we focus on three specific concepts related to platelet transfusion in the neonatal and pediatric population: choice of transfusion threshold; use of ABO-mismatched platelets; transfusion of pathogen-reduced or inactivated platelets.

Recent Findings: Recent trials support the use of lower platelet transfusion thresholds (25 000/μl) in preterm neonates, although data is limited to guide transfusion among more mature neonates. In children, there is low-level evidence as to what the prophylactic platelet transfusion threshold should be in many situations of thrombocytopenia, revealing major variability in platelet transfusion practices.

Diagnosis of acute serious illness: the role of point-of-care technologies.

Access to rapid diagnostic information is a core value of point-of-care (POC) technology. This is particularly relevant in acute, emergency, and critical care settings where diagnostic speed and precision directly guide the management of patients with potentially life-threatening conditions. Many POC diagnostics described in the literature, however, remain largely unproven and have yet to enter the market entirely.

Radiation Dose and Volume to the Pancreas and Subsequent Risk of Diabetes Mellitus: A Report from the Childhood Cancer Survivor Study.

Background: Childhood cancer survivors exposed to abdominal radiation (abdRT) are at increased risk for diabetes mellitus, but the association between risk and radiation dose and volume is unclear.

Methods: Participants included 20 762 5-year survivors of childhood cancer (4568 exposed to abdRT) and 4853 siblings. For abdRT, we estimated maximum dose to abdomen; mean doses for whole pancreas, pancreatic head, body, tail; and percent pancreas volume receiving no less than 10, 20, and 30 Gy.

Enabling mesenchymal stromal cell immunomodulatory analysis using scalable platforms.

Human mesenchymal stromal cells (hMSCs) are a promising cell source for numerous regenerative medicine and cell therapy-based applications. However, MSC-based therapies have faced challenges in translation to the clinic, in part due to the lack of sufficient technologies that accurately predict MSC potency and are viable in the context of cell manufacturing. Microfluidic platforms may provide an innovative opportunity to address these challenges by enabling multiparameter analyses of small sample sizes in a high throughput and cost-effective manner, and may provide a more predictive environment in which to analyze hMSC potency.

Improved neuropsychological outcomes following proton therapy relative to X-ray therapy for pediatric brain tumor patients.

Background: Survivors of pediatric brain tumors are at risk for impaired development in multiple neuropsychological domains. The purpose of this study was to compare neuropsychological outcomes of pediatric brain tumor patients who underwent X-ray radiotherapy (XRT) versus proton radiotherapy (PRT).

Methods: Pediatric patients who underwent either XRT or PRT and received posttreatment age-appropriate neuropsychological evaluation-including measures of intelligence (IQ), attention, memory, visuographic skills, academic skills, and parent-reported adaptive functioning-were identified.

Development of a Pediatric Fertility Preservation Program: A Report From the Pediatric Initiative Network of the Oncofertility Consortium.

Infertility is known to decrease quality of life among adults. In some cases, infertility is caused by medical conditions and/or treatments prescribed in childhood, and using methods to protect or preserve fertility may expand future reproductive possibilities. Structured programs to offer counseling about infertility risk and fertility preservation options are essential in the care of pediatric patients facing fertility-threatening conditions or treatments, yet multiple barriers to program development exist.

Feeling the Force: Measurements of Platelet Contraction and Their Diagnostic Implications.

In addition to the classical biological and biochemical framework, blood clots can also be considered as active biomaterials composed of dynamically contracting platelets, nascent polymeric fibrin that functions as a matrix scaffold, and entrapped blood cells. As platelets sense, rearrange, and apply forces to the surrounding microenvironment, they dramatically change the material properties of the nascent clot, increasing its stiffness by an order of magnitude. Hence, the mechanical properties of blood clots are intricately tied to the forces applied by individual platelets.

Microvasculature-on-a-chip for the long-term study of endothelial barrier dysfunction and microvascular obstruction in disease.

Alterations in the mechanical properties of erythrocytes occurring in inflammatory and hematologic disorders such as sickle cell disease (SCD) and malaria often lead to increased endothelial permeability, haemolysis, and microvascular obstruction. However, the associations among these pathological phenomena remain unknown. Here, we report a perfusable, endothelialized microvasculature-on-a-chip featuring an interpenetrating-polymer-network hydrogel that recapitulates the stiffness of blood-vessel intima, basement membrane self-deposition and self-healing endothelial barrier function for longer than 1 month.

Inhibition of MERTK Promotes Suppression of Tumor Growth in BRAF Mutant and BRAF Wild-Type Melanoma.

Molecularly-targeted agents have improved outcomes for a subset of patients with -mutated melanoma, but treatment of resistant and wild-type tumors remains a challenge. The MERTK receptor tyrosine kinase is aberrantly expressed in melanoma and can contribute to oncogenic phenotypes. Here we report the effect of treatment with a MERTK-selective small molecule inhibitor, UNC2025, in preclinical models of melanoma.

Pregnancy after cancer: Does timing of conception affect infant health?

Background: The objective of this retrospective cohort study was to determine whether women who conceive soon after treatment for cancer have higher risks of adverse pregnancy outcomes.

Methods: Vital records data were linked to cancer registry diagnosis and treatment information in 3 US states. Women who conceived their first pregnancy after diagnosis between ages 20 and 45 years with any invasive cancer or ductal carcinoma in situ were eligible.

Recommendations on Selection and Processing of RBC Components for Pediatric Patients From the Pediatric Critical Care Transfusion and Anemia Expertise Initiative.

Objectives: To present the recommendations and supporting literature for selection and processing of RBC products in critically ill children developed by the Pediatric Critical Care Transfusion and Anemia Expertise Initiative.

Design: Consensus conference series of international, multidisciplinary experts in RBC transfusion management of critically ill children METHODS:: The panel of 38 experts developed evidence-based, and when evidence was lacking, expert-based clinical recommendations as well as research priorities for RBC transfusions in critically ill children. The RBC processing subgroup included five experts.

Recommendations on RBC Transfusion Support in Children With Hematologic and Oncologic Diagnoses From the Pediatric Critical Care Transfusion and Anemia Expertise Initiative.

Objectives: To present the recommendations and supporting evidence for RBC transfusions in critically ill children with hematologic and oncologic disease from the Pediatric Critical Care Transfusion and Anemia Expertise Initiative.

Design: Consensus conference series of international, multidisciplinary experts in RBC transfusion management of critically ill children.

Methods: The panel of 38 experts developed evidence-based and, when evidence was lacking, expert-based clinical recommendations and research priorities for RBC transfusions in critically ill children.

Role of Tissue-Resident Memory in Intra-Tumor Heterogeneity and Response to Immune Checkpoint Blockade.

Tissue-resident memory T (T) cells are a distinct subset of memory T cells that reside in non-lymphoid tissues for prolonged periods of time without significant recirculation providing continued immune surveillance at these sites. Recent studies suggest that T cells are also enriched within tumor tissue. Expression of inhibitory immune checkpoints (ICPs) is particularly enriched on this subset of tumor-infiltrating T cells, suggesting that they are major targets for newer therapies targeting ICPs such as the programmed death-1 pathway.

3D in vitro microvascular model-based lymphoma model.

Diffuse large B-cell lymphoma (DLBCL) is a particularly aggressive cancer, impacting the lives of approximately 20,000 people annually in the United States. Elucidating cellular interactions that occur within the microenvironment of DLBCL tumors is crucial to the successful development of therapeutic strategies for this condition. As the in vivo microenvironment of DLBCL is quite complex and variable, in vitro platforms that can sufficiently recapitulate these multifaceted cellular interactions without introducing the complexities of in vivo systems are vital for understanding the pathophysiology of this disease.

Ultraviolet Hyperspectral Interferometric Microscopy.

Ultraviolet (UV) spectroscopy is a powerful tool for quantitative (bio)chemical analysis, but its application to molecular imaging and microscopy has been limited. Here we introduce ultraviolet hyperspectral interferometric (UHI) microscopy, which leverages coherent detection of optical fields to overcome significant challenges associated with UV spectroscopy when applied to molecular imaging. We demonstrate that this method enables quantitative spectral analysis of important endogenous biomolecules with subcellular spatial resolution and sensitivity to nanometer-scaled structures for label-free molecular imaging of live cells.