Association of inflammatory biomarkers with subsequent clinical course in suspected late onset sepsis in preterm neonates

Background: Sepsis is a major health issue in preterm infants. Biomarkers are used to diagnose and monitor patients with sepsis, but C-reactive protein (CRP) is proven not predictive at onset of late onset neonatal sepsis (LONS) diagnosis. The aim of this study was to evaluate the association of interleukin-6(IL-6), procalcitonin (PCT) and CRP with subsequent sepsis severity and mortality in preterm infants suspected of late onset neonatal sepsis. Methods: The study was conducted at the Erasmus University Medical Center–Sophia Children’s Hospital Rotterdam. Patient data from January 2018 until October 2019 were reviewed for all preterm neonates born with a gestational age below 32 weeks with signs and symptoms suggestive of systemic infection, in whom blood was taken for blood culture and for inflammatory biomarkers determinations. Plasma IL-6 and PCT were assessed next to CRP at the moment of suspicion. We assessed the association with 7-day mortality and sepsis severity (neonatal sequential organ failure assessment (nSOFA) score, need for inotropic support, invasive ventilation and thrombocytopenia). Results: A total of 480 suspected late onset neonatal sepsis episodes in 208 preterm neonates (gestational age < 32 weeks) were retrospectively analyzed, of which 143 episodes were classified as sepsis (29.8%), with 56 (11.7%) cases of culture negative, 63 (13.1%) cases of gram-positive and 24(5.0%) cases of gram-negative sepsis. A total of 24 (5.0%) sepsis episodes resulted in death within 7 days after suspicion of LONS. Both IL-6 (adjusted hazard ratio (aHR): 2.28; 95% CI 1.64–3.16; p < 0.001) and PCT (aHR: 2.91; 95% CI 1.70–5.00; p < 0.001) levels were associated with 7-day mortality; however, CRP levels were not significantly correlated with 7-day mortality (aHR: 1.16; 95% CI (0.68–2.00; p = 0.56). Log IL-6, log PCT and log CRP levels were all significantly correlated with the need for inotropic support. Conclusions: Our findings show that serum IL-6 and PCT levels at moment of suspected late onset neonatal sepsis offer valuable information about sepsis severity and mortality risk in infants born below 32 weeks of gestation. The discriminative value was superior to that of CRP. Determining these biomarkers in suspected sepsis may help identify patients with imminent severe sepsis, who may require more intensive monitoring and therapy

Exercise Improves Insulin Sensitivity in the Absence of Changes in Cytokines.

PURPOSE: The benefits of aerobic exercise training on insulin sensitivity in subjects with the metabolic syndrome (MetS) are, at least in part, associated with changes in cytokines. Recent studies identified novel cytokines (e.g. fractalkine, omentin and osteopontin) that are strongly involved in glucose homeostasis and therefore potentially contribute in the exercise-induced changes in insulin sensitivity. Therefore, we aim to examine changes in skeletal muscle RNA expression and plasma levels of novel cytokines after exercise training, and correlate these changes to the exercise-induced changes in insulin sensitivity. METHODS: Women with the metabolic syndrome (MetS, n=11) and healthy women (n=10) participated in a 6-month aerobic exercise training intervention (3/week, 45min per session at 65%-85% of individual heart rate reserve). Before and after training, we examined insulin sensitivity (M-value during hyperinsulinemic euglycaemic clamp), circulating blood levels of cytokines (venous blood sample; leptin, adiponectin, omentin, fraktalkin, osteopontin). Skeletal muscle RNA-expression of these cytokines (muscle biopsy) was examined in two subgroups (MetS n=6; healthy women n=6). RESULTS: At baseline, plasma levels of omentin (85.8±26.2ng/ml) and adiponectin (5.0±1.7μg/ml) levels were significantly higher in controls compared to MetS (51.1±27.1; 3.6±1.1 respectively), and leptin levels were lower in controls (18.7±11.5ng/ml vs 53.0±23.5). M-value was significantly higher in controls (8.1±1.9mg/kg/min) than in MetS (4.0±1.7). Exercise training significantly improved M-values in both groups (P0.05). CONCLUSION: Whilst exercise training successfully improves insulin sensitivity in MetS and healthy women, we found no change in plasma and mRNA expression levels of novel cytokines