A TRANSCRIPTOMIC APPRECIATION OF CHILDHOOD MENINGOCOCCAL AND POLYMICROBIAL SEPSIS FROM A PRO-INFLAMMATORY AND TRAJECTORIAL PERSPECTIVE, A ROLE FOR VASCULAR ENDOTHELIAL GROWTH FACTOR A AND B MODULATION?

ABSTRACT: This study investigated the temporal dynamics of childhood sepsis by analyzing gene expression changes associated with proinflammatory processes. Five datasets, including four meningococcal sepsis shock (MSS) datasets (two temporal and two longitudinal) and one polymicrobial sepsis dataset, were selected to track temporal changes in gene expression. Hierarchical clustering revealed three temporal phases: early, intermediate, and late, providing a framework for understanding sepsis progression. Principal component analysis supported the identification of gene expression trajectories. Differential gene analysis highlighted consistent upregulation of vascular endothelial growth factor A (VEGF-A) and nuclear factor κB1 (NFKB1), genes involved in inflammation, across the sepsis datasets. NFKB1 gene expression also showed temporal changes in the MSS datasets. In the postmortem dataset comparing MSS cases to controls, VEGF-A was upregulated and VEGF-B downregulated. Renal tissue exhibited higher VEGF-A expression compared with other tissues. Similar VEGF-A upregulation and VEGF-B downregulation patterns were observed in the cross-sectional MSS datasets and the polymicrobial sepsis dataset. Hexagonal plots confirmed VEGF-R (VEGF receptor)-VEGF-R2 signaling pathway enrichment in the MSS cross-sectional studies. The polymicrobial sepsis dataset also showed enrichment of the VEGF pathway in septic shock day 3 and sepsis day 3 samples compared with controls. These findings provide unique insights into the dynamic nature of sepsis from a transcriptomic perspective and suggest potential implications for biomarker development. Future research should focus on larger-scale temporal transcriptomic studies with appropriate control groups and validate the identified gene combination as a potential biomarker panel for sepsis.

Causality, Severity, and Avoidability of Adverse Drug Reactions in Hospitalized Children: A Prospective Cohort Study.

BACKGROUND:  Adverse drug reactions are an important cause of morbidity and mortality in all patients. Information regarding adverse drug reactions in the pediatric age group, especially with regard to the drugs involved and the clinical presentations is scanty. The aim of our study is to determine the incidence of adverse drug reactions and to study their features in terms of causality, type, severity, avoidability, drugs implicated and their clinical presentations. METHODS:  The study was carried out on patients admitted to the pediatric ward and the pediatric intensive care unit over a one-year period (January 1, 2013 to December 31, 2013). Patients either presenting with or developing an adverse drug reaction in the hospital were included in the study. RESULTS:  The incidence rate for adverse drug reaction causing hospital admission was 1.79% (95% CI 1.48, 2.16) whereas it was 1.23% (95% CI 0.97, 1.53) for children exposed to a drug during their hospital stay. Type B (bizarre or idiosyncratic type) was seen in 114 (62.6%) of the ADRs whereas 53 (29.1%) were of type A (augmented pharmacologic effect). Severe ADRs were seen in 25 (13.7%) of the total ADRs. ADR was responsible for the death of two patients. 15.4% were rated as avoidable. Anti-microbials were the most common group responsible for ADRs (43.4%), followed by drugs acting on the immune system (15.9%) and drugs acting on the nervous system (14.3%). The most common ADRs were metabolic (29.3%) followed by neurological (17.6%). CONCLUSIONS:  Adverse drug reactions can occur in a substantial proportion of hospitalized patients with some of them being severe and potentially avoidable. Awareness among physicians should be encouraged regarding monitoring, documentation and notification of adverse drug reactions.

Fetal valproate syndrome in a 2-month-old male infant.

Fetal valproate syndrome (FVS) results from prenatal exposure to valproic acid. It is characterized by a distinctive facial appearance, a cluster of minor and major anomalies and central nervous system dysfunction. We describe a 2-month-old male infant with the typical dysmorphic features characteristic of FVS. He had a persistent left superior vena cava draining into a dilated coronary sinus and mild pulmonary hypertension. There was a history of maternal intake of sodium valproate during pregnancy.