Machine Learning-based Prognostic Subgrouping of Glioblastoma: A Multi-center Study.

Background: Glioblastoma is the most aggressive adult primary brain cancer, characterized by significant heterogeneity, posing challenges for patient management, treatment planning, and clinical trial stratification.

Methods: We developed a highly reproducible, personalized prognostication and clinical subgrouping system using machine learning (ML) on routine clinical data, MRI, and molecular measures from 2,838 demographically diverse patients across 22 institutions and 3 continents. Patients were stratified into favorable, intermediate, and poor prognostic subgroups (I, II, III) using Kaplan-Meier analysis (Cox proportional model and hazard ratios [HR]).

Re-irradiation plus pembrolizumab: Phase II study for recurrent glioblastoma patients.

Purpose: Radiation therapy may enhance anti-tumor immune responses by several mechanisms including induction of immunogenic cell death. We performed a phase 2 study of pembrolizumab with re-irradiation in patients with recurrent glioblastoma.

Methods: Sixty recurrent glioblastoma patients received pembrolizumab with re-irradiation alone (cohort A, bevacizumab-naïve; n=30) or with bevacizumab continuation (cohort B, n=30).

A Prospective Phase I/II Clinical Trial of High-Dose Proton Therapy for Chordomas and Chondrosarcomas.

Purpose: The purpose of this study was to evaluate the feasibility and safety of dose-escalated proton beam therapy for treating chordomas and chondrosarcomas of the skull base and spine. Methods: A prospective cohort of 54 patients (42 with chordomas and 12 with chondrosarcomas) was enrolled between 2010 and 2018. The primary endpoints were feasibility and <20% rate of acute grade ≥3 toxicity, and secondary endpoints included cancer-specific outcomes and toxicities.

Repeated peripheral infusions of anti-EGFRvIII CAR T cells in combination with pembrolizumab show no efficacy in glioblastoma: a phase 1 trial.

We previously showed that chimeric antigen receptor (CAR) T-cell therapy targeting epidermal growth factor receptor variant III (EGFRvIII) produces upregulation of programmed death-ligand 1 (PD-L1) in the tumor microenvironment (TME). Here we conducted a phase 1 trial (NCT03726515) of CAR T-EGFRvIII cells administered concomitantly with the anti-PD1 (aPD1) monoclonal antibody pembrolizumab in patients with newly diagnosed, EGFRvIII glioblastoma (GBM) (n = 7). The primary outcome was safety, and no dose-limiting toxicity was observed.

Obesogens: a unifying theory for the global rise in obesity.

Despite varied treatment, mitigation, and prevention efforts, the global prevalence and severity of obesity continue to worsen. Here we propose a combined model of obesity, a unifying paradigm that links four general models: the energy balance model (EBM), based on calories as the driver of weight gain; the carbohydrate-insulin model (CIM), based on insulin as a driver of energy storage; the oxidation-reduction model (REDOX), based on reactive oxygen species (ROS) as a driver of altered metabolic signaling; and the obesogens model (OBS), which proposes that environmental chemicals interfere with hormonal signaling leading to adiposity. We propose a combined OBS/REDOX model in which environmental chemicals (in air, food, food packaging, and household products) generate false autocrine and endocrine metabolic signals, including ROS, that subvert standard regulatory energy mechanisms, increase basal and stimulated insulin secretion, disrupt energy efficiency, and influence appetite and energy expenditure leading to weight gain.

Delivery of re-irradiation and complex palliative radiotherapy using proton therapy in pediatric cancer patients.

Background: The intent of this study is to characterize indications for pediatric palliative-intent proton radiation therapy (PIPRT).

Procedure: We retrospectively reviewed patients 21 years and younger who received PIPRT. We defined PIPRT as radiotherapy (RT) aimed to improve cancer-related symptoms/provide durable local control in the non-curative setting.

Obesogens and Obesity: State-of-the-Science and Future Directions Summary from a Healthy Environment and Endocrine Disruptors Strategies Workshop.

On September 7 and 8, 2022, Healthy Environment and Endocrine Disruptors Strategies, an Environmental Health Sciences program, convened a scientific workshop of relevant stakeholders involved in obesity, toxicology, or obesogen research to review the state of the science regarding the role of obesogenic chemicals that might be contributing to the obesity pandemic. The workshop's objectives were to examine the evidence supporting the hypothesis that obesogens contribute to the etiology of human obesity; to discuss opportunities for improved understanding, acceptance, and dissemination of obesogens as contributors to the obesity pandemic; and to consider the need for future research and potential mitigation strategies. This report details the discussions, key areas of agreement, and future opportunities to prevent obesity.

The Metabolic Matrix: Re-engineering ultraprocessed foods to feed the gut, protect the liver, and support the brain.

Ultraprocessed food is established as a metabolic disruptor acting to increase adiposity, reduce mitochondrial efficiency, drive insulin resistance, alter growth, and contribute to human morbidity and mortality. Consumer packaged goods (CPG) companies are beginning to understand the detrimental impact of the food they market, and have employed substitution strategies to reduce salt, sugar, and fat. However, the harms of ultraprocessed foods are far more complex than any single component, and are not ameliorated by such simple substitutions.

The History of Obesity Research.

Perhaps the most unexpected development in pediatric endocrinology in the past 50 years has been the recognition of obesity as an endocrine/metabolic disorder rather than a life choice or moral failing. The history of obesity research is disjointed, having followed two separate paths in the 20th century, based on two independent yet overlapping paradigms. Proponents of the "Energy Storage" hypothesis point to data implicating monogenetic disorders, the ventromedial hypothalamus, insulin, cortisol, and the adipocyte itself in the pathogenesis of obesity.

Sex-Specific Pathways Lead to Statural Growth Impairment in Children with Crohn's Disease.

Objectives: To examine the underlying mechanisms that lead growth impairment to occur more commonly in males than females with Crohn's disease (CD).

Study Design: Children and adolescents with CD were enrolled in a prospective multicenter longitudinal cohort study. Height Z-score difference was computed as height Z-score based on chronological age (height chronological age-Z-score) minus height Z-score based on bone age (height bone age-Z-score) using longitudinal data.

Life-threatening altered mental status secondary to memantine in an adolescent undergoing cranial radiotherapy for medulloblastoma.

Introduction: Memantine is used for neurocognitive protection in patients undergoing cranial radiotherapy for central nervous system tumors and is reported to be well-tolerated.

Case Report: Presented is a case of memantine-induced altered mental status requiring an intensive care unit admission. An 18-year-old male with relapsed, progressive medulloblastoma presented with severe altered mental status shortly after the first fraction of palliative whole brain radiotherapy.

Endocrine outcomes after limited surgery and conformal photon radiation therapy for pediatric craniopharyngioma: Long-term results from the RT1 protocol.

Background: To estimate the incidence of endocrinopathy in children and adolescents with craniopharyngioma after treatment with photon-based conformal and intensity-modulated radiation therapy (CRT).

Methods: One hundred one pediatric patients were enrolled on a phase II single-institution protocol beginning in 1998 (n = 76) or followed a similar non-protocol treatment plan (n = 25). Surgery was individualized.

Effects of Isocaloric Fructose Restriction on Ceramide Levels in Children with Obesity and Cardiometabolic Risk: Relation to Hepatic De Novo Lipogenesis and Insulin Sensitivity.

Sugar intake, particularly fructose, is implicated as a factor contributing to insulin resistance via hepatic de novo lipogenesis (DNL). A nine-day fructose reduction trial, controlling for other dietary factors and weight, in children with obesity and metabolic syndrome, decreased DNL and mitigated cardiometabolic risk (CMR) biomarkers. Ceramides are bioactive sphingolipids whose dysregulated metabolism contribute to lipotoxicity, insulin resistance, and CMR.

Obesity II: Establishing causal links between chemical exposures and obesity.

Obesity is a multifactorial disease with both genetic and environmental components. The prevailing view is that obesity results from an imbalance between energy intake and expenditure caused by overeating and insufficient exercise. We describe another environmental element that can alter the balance between energy intake and energy expenditure: obesogens.

General Anesthesia for Pediatric Radiation Therapy in the Era of COVID-19.

Purpose: Managing pediatric patients requiring daily general anesthesia (GA) for radiation therapy (RT) in the setting of COVID-19 is complex, owing to the aerosolizing nature of GA procedures, the risk of cardiopulmonary complications for infected patients, and the treatment of immunocompromised oncology patients in a busy, densely populated radiation oncology clinic.

Methods And Materials: We developed an institutional protocol to define procedures for COVID-19 testing and protection of patients, caregivers, and staff, hypothesizing that this protocol would allow patients requiring GA to be safely treated, minimizing COVID-19 transmission risk to both patients and staff, and at the same time maintaining pre-COVID-19 patient volumes. All patients underwent COVID-19 testing before their first treatment and thrice weekly during treatment.

Correlation of LET With MRI Changes in Brain and Potential Implications for Normal Tissue Complication Probability for Patients With Meningioma Treated With Pencil Beam Scanning Proton Therapy.

Purpose: This study aimed to investigate the correlation between imaging changes in brain normal tissue and the spatial distribution of linear energy transfer (LET) for a cohort of patients with meningioma treated with scanned proton beams. Then, assuming imaging changes are induced by cell lethality, we studied the correlation between normal tissue complication probability and LET.

Methods And Materials: Magnetic resonance imaging T2/fluid attenuated inversion recovery acquired at different intervals after proton radiation were coregistered with the planning computed tomography (CT) images from 26 patients with meningioma with abnormalities after proton radiation therapy.

Dual-Energy Computed Tomography Proton-Dose Calculation with Scripting and Modified Hounsfield Units.

Purpose: To describe an implementation of dual-energy computed tomography (DECT) for calculation of proton stopping-power ratios (SPRs) in a commercial treatment-planning system. The process for validation and the workflow for safe deployment of DECT is described, using single-energy computed tomography (SECT) as a safety check for DECT dose calculation.

Materials And Methods: The DECT images were acquired at 80 kVp and 140 kVp and were processed with computed tomography scanner software to derive the electron density and effective atomic number images.

Longer Leukocyte Telomere Length Predicts Stronger Response to a Workplace Sugar-Sweetened Beverage Sales Ban: An Exploratory Study.

Background: Shorter leukocyte telomere length (LTL) is associated with increased risk of a number of metabolic diseases including insulin resistance and the development of type 2 diabetes mellitus. Shorter LTL is also associated with stress reactivity suggestive of a possible role for LTL to predict response to behavioral interventions. However, few studies have evaluated how interventions, such as weight loss or dietary changes, are associated with LTL changes or whether LTL can predict behavioral responses to interventions.

Childhood Overweight and Obesity and Pubertal Onset Among Mexican-American Boys and Girls in the CHAMACOS Longitudinal Study.

Secular trends in earlier initiation of puberty have been observed in recent decades. One risk factor appears to be increases in adiposity, as measured by body mass index. This trend is particularly notable among Latino populations, who have higher rates of overweight/obesity compared with non-Latino White youth.

A Brief Motivational Intervention Differentially Reduces Sugar-sweetened Beverage (SSB) Consumption.

Background: Environmental and behavioral interventions hold promise to reduce sugar-sweetened beverage (SSBs) consumption.

Purpose: To test, among frequent SSB consumers, whether motivations to consume SSBs moderated the effects of (a) a workplace SSB sales ban (environmental intervention) alone, and (b) a "brief motivational intervention" (BI) in addition to the sales ban, on changes in SSB consumption.

Methods: We assessed whether (1) baseline motivations to consume SSBs (craving, psychological stress, or taste enjoyment) impacted changes in daily SSB consumption at 6-month follow-up among frequent (>12oz of SSBs/day) SSB consumers (N = 214); (2) participants randomized to the BI (n = 109) versus to the sales ban only (n = 105) reported greater reductions in SSB consumption at follow-up; and (3) motivations to consume SSBs moderated any changes in SSB consumption.