Newborn patients exhibit an unusual pattern of interleukin 10 and interferon γ serum levels in response to cardiac surgery

AbstractObjective: The aim of this study was to determine the clinical significance of serum levels of interleukin 10 and interferon γ in pediatric patients undergoing cardiopulmonary bypass. Methods: We divided the patients into 2 groups: 8 neonates and 19 nonnewborn children. Interleukin 10 and interferon γ serum levels were quantified before sternotomy, at admission to the pediatric intensive care unit (30 minutes postoperatively), 24 hours after the onset of the operation, and 3 days after the operation. Results: Newborn patients displayed significantly greater amounts of serum interleukin 10 than older children, not only in regard to the peak level achieved but also at every postoperative time point analyzed. In contrast, no significant changes in interferon γ serum levels were observed in neonates at any time point, whereas nonnewborn pediatric patients showed a significant increase in interferon γ serum concentrations immediately after the operation. This unusual pattern of cytokine response in newborn patients was not associated with modifications in cortisol serum levels. Furthermore, although neonates had significantly different surgical and clinical variables than did the nonnewborn pediatric patients, the variation in interleukin 10 production in neonates could not be accounted for by differences in the magnitude of surgical injury. In the group of neonates, there were significant positive correlations between peak interleukin 10 serum levels and both partial pressure of arterial oxygen/fraction of inspired oxygen ratio and postoperative body weight gain. Conclusions: Newborn patients undergoing cardiopulmonary bypass exhibit a distinctive biologic response pattern characterized by high levels of serum interleukin 10 without changes in serum interferon γ. This cytokine imbalance could have potential clinical implications.J Thorac Cardiovasc Surg 2002;123:451-

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar

Mapping and predicting mortality from systemic sclerosis

Objectives To determine the causes of death and risk factors in systemic sclerosis (SSc). Methods Between 2000 and 2011, we examined the death certificates of all French patients with SSc to determine causes of death. Then we examined causes of death and developed a score associated with all-cause mortality from the international European Scleroderma Trials and Research (EUSTAR) database. Candidate prognostic factors were tested by Cox proportional hazards regression model by single variable analysis, followed by a multiple variable model stratified by centres. The bootstrapping technique was used for internal validation. Results We identified 2719 French certificates of deaths related to SSc, mainly from cardiac (31%) and respiratory (18%) causes, and an increase in SSc-specific mortality over time. Over a median follow-up of 2.3 years, 1072 (9.6%) of 11 193 patients from the EUSTAR sample died, from cardiac disease in 27% and respiratory causes in 17%. By multiple variable analysis, a risk score was developed, which accurately predicted the 3-year mortality, with an area under the curve of 0.82. The 3-year survival of patients in the upper quartile was 53%, in contrast with 98% in the first quartile. Conclusion Combining two complementary and detailed databases enabled the collection of an unprecedented 3700 deaths, revealing the major contribution of the cardiopulmonary system to SSc mortality. We also developed a robust score to risk-stratify these patients and estimate their 3-year survival. With the emergence of new therapies, these important observations should help caregivers plan and refine the monitoring and management to prolong these patients' survival. ©Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted