Paediatric Personalized Research Network Switzerland (SwissPedHealth): a joint paediatric national data stream.

Introduction: Children represent a large and vulnerable patient group. However, the evidence base for most paediatric diagnostic and therapeutic procedures remains limited or is often inferred from adults. There is an urgency to improve paediatric healthcare provision based on real-world evidence generation.

Early detection of neonatal sepsis and reduction of overall antibiotic exposure: Towards precision medicine.

Infections claim the lives of over half a million newborns annually and expose survivors to the risk of lifelong disability. The challenge to clinicians is to identify newborns with invasive infections rapidly, promptly initiate antimicrobial treatment, and take measures to prevent and treat organ dysfunction. Moreover, excessive antibiotic use is a global public health problem.

Antibiotic exposure for culture-negative early-onset sepsis in late-preterm and term newborns: an international study.

Background: Early-life antibiotic exposure is disproportionately high compared to the burden of culture-proven early-onset sepsis (CP-EOS). We assessed the contribution of culture-negative cases to the overall antibiotic exposure in the first postnatal week.

Methods: We conducted a retrospective analysis across eleven countries in Europe, North America, and Australia.

Adapt and shape: metabolic features within the metastatic niche.

The success of disseminating cancer cells (DTCs) at specific metastatic sites is influenced by several metabolic factors. Even before DTCs arrival, metabolic conditioning from the primary tumor participates in creating a favorable premetastatic niche at distant organs. In addition, DTCs adjust their metabolism to better survive along the metastatic journey and successfully colonize their ultimate destination.

Sepsis shapes the human γδ TCR repertoire in an age- and pathogen-dependent manner.

Sepsis affects 25 million children per year globally, leading to 2.9 million deaths and substantial disability in survivors. Extensive characterization of interactions between the host and bacteria in children is required to design novel preventive and therapeutic strategies tailored to this age group.

FADS1/2 control lipid metabolism and ferroptosis susceptibility in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) has limited therapeutic options, is highly metastatic and characterized by early recurrence. Lipid metabolism is generally deregulated in TNBC and might reveal vulnerabilities to be targeted or used as biomarkers with clinical value. Ferroptosis is a type of cell death caused by iron-dependent lipid peroxidation which is facilitated by the presence of polyunsaturated fatty acids (PUFA).

Lactate supports cell-autonomous ECM production to sustain metastatic behavior in prostate cancer.

Extracellular matrix (ECM) is a major component of the tumor environment, promoting the establishment of a pro-invasive behavior. Such environment is supported by both tumor- and stromal-derived metabolites, particularly lactate. In prostate cancer (PCa), cancer-associated fibroblasts (CAFs) are major contributors of secreted lactate, able to impact on metabolic and transcriptional regulation in cancer cells.

Acetyl-CoA carboxylase 1 controls a lipid droplet-peroxisome axis and is a vulnerability of endocrine-resistant ER breast cancer.

Targeting aromatase deprives ER breast cancers of estrogens and is an effective therapeutic approach for these tumors. However, drug resistance is an unmet clinical need. Lipidomic analysis of long-term estrogen-deprived (LTED) ER breast cancer cells, a model of aromatase inhibitor resistance, revealed enhanced intracellular lipid storage.

The changing clinical presentation of COVID-19 in children during the course of the pandemic.

Aim: To investigate the evolution of clinical symptoms of COVID-19 in children throughout the pandemic.

Methods: In this national prospective surveillance study, symptoms in children hospitalised with COVID-19 were collected from all paediatric hospitals in Switzerland between March 2020 and March 2023. Data was analysed across four time periods, according to the predominantly circulating SARS-CoV-2 variant: T1 (wild-type), T2 (Alpha), T3 (Delta) and T4 (Omicron), as well as by age group.

Dysregulated monocyte-derived macrophage response to Group B in newborns.

Introduction: (Group B , GBS) is a leading pathogen of neonatal sepsis. The host-pathogen interactions underlying the progression to life-threatening infection in newborns are incompletely understood. Macrophages are first line in host defenses against GBS, contributing to the initiation, amplification, and termination of immune responses.

Organ Dysfunction in Children With Blood Culture-Proven Sepsis: Comparative Performance of Four Scores in a National Cohort Study.

Objectives: Previous studies applying Sepsis-3 criteria to children were based on retrospective analyses of PICU cohorts. We aimed to compare organ dysfunction criteria in children with blood culture-proven sepsis, including emergency department, PICU, and ward patients, and to assess relevance of organ dysfunctions for mortality prediction.

Design: We have carried out a nonprespecified, secondary analysis of a prospective dataset collected from September 2011 to December 2015.

Sensitivity of ICD coding for sepsis in children-a population-based study.

Background: International Classification of Diseases 10th edition (ICD-10) is widely used to describe the burden of disease.

Aim: To describe how well ICD-10 coding captures sepsis in children admitted to the hospital with blood culture-proven bacterial or fungal infection and systemic inflammatory response syndrome.

Methods: Secondary analysis of a population-based, multicenter, prospective cohort study on children with blood culture-proven sepsis of nine tertiary pediatric hospitals in Switzerland.

Game changer or gimmick: inflammatory markers to guide antibiotic treatment decisions in neonatal early-onset sepsis.

Background: The diagnosis of neonatal early-onset sepsis (EOS) is challenging, and inflammatory markers are widely used to guide decision-making and therapies.

Objectives: This narrative review presents the current state of knowledge regarding the diagnostic value and potential pitfalls in the interpretation of inflammatory markers for EOS.

Sources: PubMed until October 2022 and searched references in identified articles using the search terms: neonatal EOS, biomarker or inflammatory marker, and antibiotic therapy or antibiotic stewardship.

Analysis of Antibiotic Exposure and Early-Onset Neonatal Sepsis in Europe, North America, and Australia.

Importance: Appropriate use of antibiotics is life-saving in neonatal early-onset sepsis (EOS), but overuse of antibiotics is associated with antimicrobial resistance and long-term adverse outcomes. Large international studies quantifying early-life antibiotic exposure along with EOS incidence are needed to provide a basis for future interventions aimed at safely reducing neonatal antibiotic exposure.

Objective: To compare early postnatal exposure to antibiotics, incidence of EOS, and mortality among different networks in high-income countries.

Fetal Omphalocele: Review of Predictive Factors Important for Antenatal Counseling?

Importance: Congenital omphalocele is among the most common antenatally diagnosed anomalies. As additional abnormalities are found in majority of cases, antenatal investigations target the search for additional structural anomalies and genetic disorders, including aneuploidy. Antenatal management focuses on the assessment of fetal well-being.

Nutritional and metabolic signalling through GPCRs.

Deregulated metabolism is a well-known feature of several challenging diseases, including diabetes, obesity and cancer. Besides their important role as intracellular bioenergetic molecules, dietary nutrients and metabolic intermediates are released in the extracellular environment. As such, they may achieve unconventional roles as hormone-like molecules by activating cell surface G-protein-coupled receptors (GPCRs) that regulate several pathophysiological processes.

Serum Ascorbic Acid and Thiamine Concentrations in Sepsis: Secondary Analysis of the Swiss Pediatric Sepsis Study.

Objectives: To determine circulating levels of ascorbic acid (VitC) and thiamine (VitB1) in neonates and children with blood culture-proven sepsis.

Design: Nested single-center study of neonates and children prospectively included in the Swiss Pediatric Sepsis Study.

Setting: One tertiary care academic hospital.

Lactate Rewires Lipid Metabolism and Sustains a Metabolic-Epigenetic Axis in Prostate Cancer.

Unlabelled: Lactate is an abundant oncometabolite in the tumor environment. In prostate cancer, cancer-associated fibroblasts (CAF) are major contributors of secreted lactate, which can be taken up by cancer cells to sustain mitochondrial metabolism. However, how lactate impacts transcriptional regulation in tumors has yet to be fully elucidated.