MRD4U: A path to development for personalized liquid biopsy for children with central nervous system tumors.

Background: Liquid biopsy assays using cerebrospinal fluid (CSF) can revolutionize care for children with central nervous system (CNS) tumors by enabling precise monitoring of therapeutic responses and detecting recurrence or measurable residual disease (MRD). These assays can detect cell-free, circulating tumor DNA (ctDNA) via somatic alterations, though accurately measuring low-abundance ctDNA in CSF is challenging.

Methods: Our research focused on the optimization of next-generation sequencing library preparation from cell-free DNA (cfDNA), evaluating four commercial kits to address the low nucleic acid yield in CSF-derived cfDNA.

Exercise professionals in extended scope of practice roles: a qualitative exploration of a new model of rehabilitation.

Background: There is a need to provide greater patient choice through accessible and sustainable rehabilitation for people with long-term conditions. New models of rehabilitation employing non-clinical healthcare workers in extended service practice roles are developing. Little research has investigated the experiences of non-clinical health workers, such as exercise professionals, in extended scope of practice roles.

Online rehabilitation in adult Fontan patients: Effects in functional capacity, lymphatic function and quality of life.

Introduction: Survival rates for post-Fontan patients have improved, allowing many to reach adulthood with better quality of life (QOL). However, they remain at risk for reduced functional capacity (FC), skeletal muscle loss, and lymphatic dysfunction, which negatively affect clinical outcomes. This study evaluated the feasibility of an online rehabilitation program for adult Fontan patients in the late postoperative period and its effects on FC, peripheral lymphatic function (PLF), and QOL.

Comprehensive Genomic Characterization of Congenital and Infantile Cancers Reveals High Yield of Medically Meaningful Findings.

Purpose: We describe findings from genomic profiling of tumors among infantile pediatric patients studied within a translational research protocol established at our pediatric tertiary care center. Comprehensive genomic profiling was initiated to aid in diagnosis, prognostication, treatment, and detection of germline disease predisposition in this patient cohort.

Methods: Enhanced exome sequencing of disease and comparator tissue was coupled with RNA sequencing of the disease-involved specimen to assess for single nucleotide variation, insertion/deletions, copy number alteration, structural variation, fusions, and methylation profiling-based tumor classification scores.

Reduced Lymphatic Activity During Positive Pressure Ventilation and General Anesthesia-A Cause of Postoperative Edema?

Background: Edema is a common problem after long surgery or intensive care stays. The use of mechanical ventilation could be a contributing factor. The lymphatic system is responsible for draining the interstitial fluid throughout the body and is probably dependent on the outflow pressure at the lymphovenous junctions.

30-Year Survival After the Fontan Operation in Denmark.

This study aimed to evaluate the nationwide 30-year survival among Danish univentricular heart patients who underwent Fontan completion between 1977 and 2023. Secondary objectives included assessment of the impact of era, Fontan type, and ventricular dominance on survival. Finally, clinical performance and the prevalence of select morbidity were described for survivors.

Systemic Changes in Adults With a Fontan Circulation: Insights From the Plasma Proteome.

Background: Despite multiple surgeries and extensive follow-up, individuals with a univentricular heart have significant residual morbidity and mortality throughout life. By applying a state-of-the-art characterization of the plasma proteome, this study aimed at providing a comprehensive insight into the proteomic impact of living with a Fontan circulation.

Methods And Results: This study enrolled individuals with a Fontan circulation and compared them 2:1 with healthy controls.

The role of accidental hypothermia in drowning patients with out-of-hospital cardiac arrest: A nationwide registry-based cohort study.

Aim: This study aimed to investigate the associations between hypothermia and mortality or poor neurological outcome in a nationwide cohort of drowning patients with out-of-hospital cardiac arrest (OHCA).

Methods: This nationwide, registry-based cohort study reported in-hospital data on drowning patients with OHCA following the Utstein Style For Drowning. Drowning patients with OHCA were identified in the Danish Cardiac Arrest Registry from 2016 to 2021.

Lung volumes are increased in fetuses with transposition of the great arteries on intrauterine MRI.

Fetal brain size is decreased in some children with complex CHDs, and the distribution of blood and accompanying oxygen and nutrients is regionally skewed from early fetal life dependent on the CHD. In transposition of the great arteries, deoxygenated blood preferentially runs to the brain, whereas the more oxygenated blood is directed towards the lungs and the abdomen. Knowledge of whether this impacts intrauterine organ development is limited.

Multiomic profiling identifies predictors of survival in African American patients with acute myeloid leukemia.

Genomic profiles and prognostic biomarkers in patients with acute myeloid leukemia (AML) from ancestry-diverse populations are underexplored. We analyzed the exomes and transcriptomes of 100 patients with AML with genomically confirmed African ancestry (Black; Alliance) and compared their somatic mutation frequencies with those of 323 self-reported white patients with AML, 55% of whom had genomically confirmed European ancestry (white; BeatAML). Here we find that 73% of 162 gene mutations recurrent in Black patients, including a hitherto unreported PHIP alteration detected in 7% of patients, were found in one white patient or not detected.

Lymphatic morphology and function in chronic right heart failure due to secondary tricuspid valve regurgitation.

Background: In heart failure, the capacity of the lymphatic system dictates symptoms of circulatory congestion. This study aimed at describing structural and functional changes of the lymphatic system in patients with chronic right-sided heart failure.

Methods: Individuals with long-standing severe tricuspid valve regurgitation and symptoms of heart failure were compared with age- gender- and weight-matched controls.

Germline susceptibility from broad genomic profiling of pediatric brain cancers.

Background: Identifying germline predisposition in CNS malignancies is of increasing clinical importance, as it contributes to diagnosis and prognosis, and determines aspects of treatment. The inclusion of germline testing has historically been limited due to challenges surrounding access to genetic counseling, complexity in acquiring a germline comparator specimen, concerns about the impact of findings, or cost considerations. These limitations were further defined by the breadth and scope of clinical testing to precisely identify complex variants as well as concerns regarding the clinical interpretation of variants including those of uncertain significance.

Public discourse and wilful incommensurability: a case for attentive free speech.

Many thinkers lament the decline of liberal democracy. Some argue that, to rejuvenate it, we must think big. Thinking big involves generating new ideas about how to achieve an unprecedented level of social transformation aimed at cultivating solidarity, empowering citizen efficacy, and promoting the common good.

The association of smoking with different eating and dietary behaviours: A cross-sectional analysis of 80 296 United Kingdom adults.

Background And Aims: Smokers typically have a lower body mass index (BMI) than non-smokers, while smoking cessation is associated with weight gain. In pre-clinical research, nicotine in tobacco smoking suppresses appetite and influences subsequent eating behaviour; however, this relationship is unclear in humans. This study measured the associations of smoking with different eating and dietary behaviours.

Sequential MRI Evaluation of Lymphatic Abnormalities over the Course of Fontan Completion.

Purpose To evaluate lymphatic abnormalities before and after Fontan completion using noncontrast lymphatic imaging and relate findings with postoperative outcomes. Materials and Methods This study is a retrospective review of noncontrast T2-weighted lymphatic imaging performed at The Children's Hospital of Philadelphia from June 2012 to February 2023 in patients with single ventricle physiology. All individuals with imaging at both pre-Fontan and Fontan stages were eligible.

Salivary gland carcinosarcoma ex pleomorphic adenoma: a case report with molecular characterization.

True malignant mixed tumors, also known as salivary gland carcinosarcoma (SCS), are uncommon yet highly aggressive lesions associated with a poor prognosis. These tumors exhibit a distinctive biphasic structure characterized by both epithelial and mesenchymal components. Recent research has shown that the majority of SCS cases stem from pre-existing pleomorphic adenomas (PAs), suggesting a stepwise developmental pattern.

Increase in Full-Length Dystrophin by Exon Skipping in Duchenne Muscular Dystrophy Patients with Single Exon Duplications: An Open-label Study.

Single exon duplications account for disease in a minority of Duchenne muscular dystrophy patients. Exon skipping in these patients has the potential to be highly therapeutic through restoration of full-length dystrophin expression. We conducted a 48-week open label study of casimersen and golodirsen in 3 subjects with an exon 45 or 53 duplication.

Full-length isoform concatenation sequencing to resolve cancer transcriptome complexity.

Background: Cancers exhibit complex transcriptomes with aberrant splicing that induces isoform-level differential expression compared to non-diseased tissues. Transcriptomic profiling using short-read sequencing has utility in providing a cost-effective approach for evaluating isoform expression, although short-read assembly displays limitations in the accurate inference of full-length transcripts. Long-read RNA sequencing (Iso-Seq), using the Pacific Biosciences (PacBio) platform, can overcome such limitations by providing full-length isoform sequence resolution which requires no read assembly and represents native expressed transcripts.

Quality of Life in the Danish Fontan Population is Unchanged Over the Past Decade-A Nationwide Longitudinal Study.

Knowledge about health-related quality of life (HRQoL) over time in Fontan patients is sparse. We aimed to describe HRQoL over a ten-year period in a population-based Fontan cohort. Further, we compared HRQoL in Fontan patients with the general population.

Exercise capacity in the Danish Fontan population remains stable after ten years of follow-up - is physical activity the key to success?

Background: Most Fontan patients have impaired exercise capacity, and a further decline in exercise capacity over time seems inevitable. However, few longitudinal studies exist, and there is a lack of data from newer eras. We aimed to describe the natural evolution of exercise capacity over a 10-year period in a contemporary, population-based cohort of Danish Fontan patients.