Predicting the preventable: Social drivers of health on pediatric readmissions and emergency department visits.

Objective: This study aimed to examine the extent to which pediatric emergency department visits and admissions are preventable and whether caregiver-reported social factors predict future preventable visits.

Method: Caregivers of hospitalized children ( = 249) completed a predischarge survey regarding health care utilization and social drivers of health (e.g.

Evaluating representativeness: recruitment for a virtual family-based intervention focused on the transition from pediatric to adult diabetes care†.

Objective: Recruiting representative samples of youth for behavioral health interventions is challenging yet necessary to translate research into practice and eliminate health disparities. Transition-aged youth with type 1 diabetes (T1D) represent a vulnerable population; not enough attention is given to their inclusion in behavioral health interventions. Behavioral Family Systems Therapy for Diabetes Transition (BFST-DT) is an intervention aimed at improving transition readiness and is currently being pilot tested.

Health Equity Intervention for Youth with Type 1 Diabetes and High Social Risk.

Background/objectives: Youth with type 1 diabetes (T1D) who experience avoidable complications often have dangerously high and consistently elevated HbA1c values. Novel Interventions in Children's Healthcare (NICH), a program designed to effectively intervene with this population, has demonstrated success with reducing avoidable complications and improving HbA1c in these youth. However, prior examinations of program outcomes have not included a comparison group.

Underresourced Youth With Diabetes in a Community-Based Intervention Show Improved Diabetes Outcomes, Technology Use, and Psychosocial Functioning.

Objective: The primary objective of this study was to evaluate the first full-scale implementation of the behavioral health program Novel Interventions in Children's Healthcare (NICH) in racially and ethnically diverse youth with diabetes and high degrees of social risk. We hypothesized that youth would demonstrate improved health outcomes and psychosocial functioning following program involvement.

Methods: Youth with diabetes who enrolled in NICH (n = 26) and their caregivers completed measures of diabetes distress, depression, and diabetes strengths prior to and following program enrollment.

Focused on the Family: Development of a Family-Based Intervention Promoting the Transition to Adult Health Care for Adolescents with Type 1 Diabetes.

There is minimal evidence for current interventions promoting the transition to adult healthcare for youth with type 1 diabetes (T1D). Few interventions exclusively target modifiable individual and family-based factors that contribute to transition readiness. The purpose of this paper is to describe the development of Behavioral Family Systems Therapy for Diabetes Transition (BFST-DT), a virtual family-based transition readiness intervention for adolescents with T1D.

Osteosarcoma cells depend on MCL-1 for survival, and osteosarcoma metastases respond to MCL-1 antagonism plus regorafenib in vivo.

Osteosarcoma is the most common form of primary bone cancer, which primarily afflicts children and adolescents. Chemotherapy, consisting of doxorubicin, cisplatin and methotrexate (MAP) increased the 5-year osteosarcoma survival rate from 20% to approximately 60% by the 1980s. However, osteosarcoma survival rates have remained stagnant for several decades.

Towards targeting the breast cancer immune microenvironment.

The tumour immune microenvironment is shaped by the crosstalk between cancer cells, immune cells, fibroblasts, endothelial cells and other stromal components. Although the immune tumour microenvironment (TME) serves as a source of therapeutic targets, it is also considered a friend or foe to tumour-directed therapies. This is readily illustrated by the importance of T cells in triple-negative breast cancer (TNBC), culminating in the advent of immune checkpoint therapy in combination with cytotoxic chemotherapy as standard of care for both early and advanced-stage TNBC, as well as recent promising signs of efficacy in a subset of hormone receptor-positive disease.

The anti-cancer immune response in breast cancer: current and emerging biomarkers and treatments.

Triple-negative breast cancers (TNBCs) exhibit heightened T cell infiltration, contributing to an enhanced response to immune checkpoint blockade (ICB) compared with other subtypes. An immune-rich immune microenvironment correlates with improved prognosis in early and advanced TNBC. Combination chemotherapy and ICB is now the standard of care in early- and late-stage TNBC.

Social Determinants of Health Screening in Type 1 Diabetes Management.

Type 1 diabetes management is intricately influenced by social determinants of health. Economic status impacts access to vital resources like insulin and diabetes technology. Racism, social injustice, and implicit biases affect equitable delivery of care.

Caregiver Experiences in Pediatric Hospitalizations: Challenges and Opportunities for Improvement.

Background: There are limited qualitative data describing general pediatric hospitalizations through the caregivers' lens, and most focus on one particular challenge or time during the hospitalization. This qualitative study aimed to address a gap in the description of the breadth and depth of personal challenges caregivers may face during the entire hospitalization, irrespective of severity of patient illness or diagnosis, and explored caregiver-suggested interventions.

Methods: Caregivers of pediatric patients on the hospitalist service at a Pacific Northwest children's hospital were interviewed to explore their hospitalization experience and solicit feedback for potential interventions.

Simulated large joint fluid model for evaluating intra-articular antibiotic delivery systems: initial evaluation using antibiotic-loaded calcium sulfate beads.

: Local antimicrobial delivery via calcium sulfate (CaSO ) beads is used as an adjunctive treatment for periprosthetic joint infection. There is limited clinical information describing the performance of antimicrobial-loaded CaSO (ALCS) in large-scale applications. We developed a simulated large joint model to study properties of eluting ALCS.

Recent and Ongoing Research into Metastatic Osteosarcoma Treatments.

The survival rate for metastatic osteosarcoma has not improved for several decades, since the introduction and refinement of chemotherapy as a treatment in addition to surgery. Over two thirds of metastatic osteosarcoma patients, many of whom are children or adolescents, fail to exhibit durable responses and succumb to their disease. Concerted efforts have been made to increase survival rates through identification of candidate therapies via animal studies and early phase trials of novel treatments, but unfortunately, this work has produced negligible improvements to the survival rate for metastatic osteosarcoma patients.

Patterns of genomic interrelatedness of publicly available samples in the TB portals database.

The TB Portals program is an international collaboration for the collection and dissemination of tuberculosis data from patient cases focused on drug resistance. The central database is a patient-oriented resource containing both patient and pathogen clinical and genomic information. Herein we provide a summary of the pathogen genomic data available through the TB Portals and show one potential application by examining patterns of genomic pairwise distances.

Below the Surface: Caregivers' Experience of Hospital-to-Home Transitions.

Objective: Our aim was to understand the breadth of the hospital-to-home experience from the caregiver perspective using a mixed method approach.

Methods: Caregivers of children who experienced an inpatient admission (N = 184) completed a hospital-to-home transition questionnaire after discharge. Twenty-six closed-ended survey items captured child's hospitalization, discharge, and postdischarge experiences and were analyzed using descriptive statistics.

ssDNA nanotubes for selective targeting of glioblastoma and delivery of doxorubicin for enhanced survival.

Effective treatment of glioblastoma remains a daunting challenge. One of the major hurdles in the development of therapeutics is their inability to cross the blood-brain tumor barrier (BBTB). Local delivery is an alternative approach that can still suffer from toxicity in the absence of target selectivity.

Establishment and Characterisation of Metastatic Extraskeletal Ewing Sarcoma Mouse Models.

Background/aim: Ewing sarcomas most commonly arise in the bones, but can also manifest as extraskeletal tumours in soft tissues. Metastases from extraskeletal Ewing sarcomas occur in more diverse anatomical sites than skeletal tumours, and have poorer survival rates. Few animal models replicate the extraskeletal form of Ewing sarcoma, and those that have been developed do not reflect the widespread metastatic spread of these cancers.

Biallelic variants of cause dose-dependent childhood-onset pulmonary arterial hypertension characterised by extreme morbidity and mortality.

Background: The molecular genetic basis of pulmonary arterial hypertension (PAH) is heterogeneous, with at least 26 genes displaying putative evidence for disease causality. Heterozygous variants in the gene were recently identified as a new cause of adult-onset PAH. However, the contribution of risk alleles to child-onset PAH remains largely unexplored.

The smac mimetic LCL161 targets established pulmonary osteosarcoma metastases in mice.

Osteosarcoma is the most common form of primary bone cancer and frequently metastasizes to the lungs. Current therapies fail to successfully treat over two thirds of patients with metastatic osteosarcoma, so there is an urgent imperative to develop therapies that effectively target established metastases. Smac mimetics are drugs that work by inhibiting the pro-survival activity of IAP proteins such as cIAP1 and cIAP2, which can be overexpressed in osteosarcomas.

The Role of Caregiver-Reported Risks in Predicting Adverse Pediatric Outcomes.

Objective: Certain social risk factors (e.g., housing instability, food insecurity) have been shown to directly and indirectly influence pediatric health outcomes; however, there is limited understanding of which social factors are most salient for children admitted to the hospital.

Tetrazolium reduction assays under-report cell death provoked by clinically relevant concentrations of proteasome inhibitors.

High throughput cell viability screening assays often capitalize on the ability of active enzymes or molecules within viable cells to catalyze a quantifiable chemical reaction. The tetrazolium reduction (MTT) assay relies on oxidoreductases to reduce tetrazolium into purple formazan crystals that are solubilized so absorbance reflects viability, while other assays use cellular ATP to catalyze a luminescence-emitting reaction. It is therefore important to know how accurately these assays report cellular responses, as cytotoxic anti-cancer agents promote cell death via a variety of signaling pathways, some of which may alter how these assays work.

The Proteasome Inhibitor Ixazomib Inhibits the Formation and Growth of Pulmonary and Abdominal Osteosarcoma Metastases in Mice.

Osteosarcoma is the most common form of primary bone cancer. Over 20% of osteosarcoma patients present with pulmonary metastases at diagnosis, and nearly 70% of these patients fail to respond to treatment. Previous work revealed that human and canine osteosarcoma cell lines are extremely sensitive to the therapeutic proteasome inhibitor bortezomib in vitro.

Transient NK Cell Depletion Facilitates Pulmonary Osteosarcoma Metastases After Intravenous Inoculation in Athymic Mice.

Two thirds of metastatic osteosarcoma patients die within 5 years of diagnosis. Improved experimental models of osteosarcoma metastasis will facilitate the development of more effective therapies. Intravenous cancer cell injection can produce lung metastases in nude mice, but this "experimental metastasis" technique has been predominantly applied to a single osteosarcoma cell line (143B) and required injection of 1-2 million cells.

Identification of Caregiver-Reported Social Risk Factors in Hospitalized Children.

Objectives: Although health systems are increasingly moving toward addressing social determinants of health, social risk screening for hospitalized children is largely unexplored. We sought to determine if inpatient screening was feasible and describe the prevalence of social risk among children and caregivers, with special attention given to children with chronic conditions.

Methods: Caregivers of pediatric patients on the hospitalist service at a children's hospital in the Pacific Northwest completed a social risk survey in 2017.

Smac mimetics LCL161 and GDC-0152 inhibit osteosarcoma growth and metastasis in mice.

Background: Current therapies fail to cure over a third of osteosarcoma patients and around three quarters of those with metastatic disease. "Smac mimetics" (also known as "IAP antagonists") are a new class of anti-cancer agents. Previous work revealed that cells from murine osteosarcomas were efficiently sensitized by physiologically achievable concentrations of some Smac mimetics (including GDC-0152 and LCL161) to killing by the inflammatory cytokine TNFα in vitro, but survived exposure to Smac mimetics as sole agents.

Proteasome inhibitors trigger mutations via activation of caspases and CAD, but mutagenesis provoked by the HDAC inhibitors vorinostat and romidepsin is caspase/CAD-independent.

Genotoxic anti-cancer therapies such as chemotherapy and radiotherapy can contribute to an increase in second malignancies in cancer survivors due to their oncogenic effects on non-cancerous cells. Inhibition of histone deacetylase (HDAC) proteins or the proteasome differ from chemotherapy in that they eliminate cancer cells by regulating gene expression or cellular protein equilibrium, respectively. As members of these drug classes have been approved for clinical use in recent times, we investigated whether these two drug classes exhibit similar mutagenic capabilities as chemotherapy.