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. PATIENTS: Sixty-one neonates and children 0-16 years old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: VitC and VitB1 were quantified in serum of patients (median age, 10.5 mo; interquartile range [IQR], 0.5-62.1 mo) with blood culture-proven sepsis. Median time between sepsis onset and sampling for measurement of vitamins was 3 days (IQR, 2-4 d). Median serum levels of VitC and VitB1 were 32.4 µmol/L (18.9-53.3 µmol/L) and 22.5 nmol/L (12.6-82 nmol/L); 36% of the patients (22/61) had low VitC and 10% (6/61) had VitC deficiency; and 72% (44/61) had low VitB1 and 13% (8/61) had VitB1 deficiency. Children with low VitC were older (p = 0.007) and had higher C-reactive protein (p = 0.004) compared with children with VitC within the normal range. Children with low VitB1 levels were older (p = 0.0009) and were less frequently receiving enteral or parenteral vitamin supplementation (p = 0.0000003) compared with children with normal VitB1 levels. CONCLUSIONS: In this cohort of newborns and children with sepsis, low and deficient VitC and VitB1 levels were frequently observed. Age, systemic inflammation, and vitamin supplementation were associated with vitamin levels during sepsis.

Tenascin-C inactivation impacts lung structure and function beyond lung development.

Tenascin-C (TNC) is an extracellular matrix protein expressed at high levels during lung organogenesis. Later, TNC is only transiently de novo expressed to orchestrate tissue repair in pathological situations. We previously showed that TNC inactivation affects lung development and thus evaluated here the implications on lung function in newborn/adult mice. Respiratory function parameters were measured in anesthetized and mechanically ventilated wild-type (WT) and TNC-deficient mice at 5 (P5) and 90 (P90) days of age under basal conditions, as well as following high tidal volume (HTV) ventilation. At P5, TNC-deficient mice showed an increased static compliance (Cst) and inspiratory capacity (IC) relative to WT at baseline and throughout HTV. At P90, however, Cst and IC were only elevated at baseline. Control non-ventilated newborn and adult TNC-deficient mice showed similar lung morphology, but less alpha smooth muscle actin (α-SMA) around small airways. SMA + cells were decreased by 50% in adult TNC-deficient lungs and collagen layer thickened around small airways. Increased surfactant protein C (SP-C) and altered TGFß and TLR4 signaling pathways were also detected. Thus, TNC inactivation-related defects during organogenesis led to persisting functional impairment in adulthood. This might be of interest in the context of pulmonary diseases with thickened airway smooth muscle layer or ventilation heterogeneity, like asthma and COPD.