Performance of 11 Host Biomarkers Alone or in Combination in the Diagnosis of Late-Onset Sepsis in Hospitalized Neonates: The Prospective EMERAUDE Study.

Despite the high prevalence of late-onset sepsis (LOS) in neonatal intensive care units, a reliable diagnosis remains difficult. This prospective, multicenter cohort study aimed to identify biomarkers early to rule out the diagnosis of LOS in 230 neonates ≥7 days of life with signs of suspected LOS. Blood levels of eleven protein biomarkers (PCT, IL-10, IL-6, NGAL, IP-10, PTX3, CD14, LBP, IL-27, gelsolin, and calprotectin) were measured. Patients received standard of care blinded to biomarker results, and an independent adjudication committee blinded to biomarker results assigned each patient to either infected, not infected, or unclassified groups. Performances of biomarkers were assessed considering a sensitivity of at least 0.898. The adjudication committee classified 22% of patients as infected and all of these received antibiotics. A total of 27% of the not infected group also received antibiotics. The best biomarkers alone were IL-6, IL-10, and NGAL with an area under the curve (95% confidence interval) of 0.864 (0.798-0.929), 0.845 (0.777-0.914), and 0.829 (0.760-0.898), respectively. The best combinations of up to four biomarkers were PCT/IL-10, PTX3/NGAL, and PTX3/NGAL/gelsolin. The best models of biomarkers could have identified not infected patients early on and avoided up to 64% of unjustified antibiotics. At the onset of clinical suspicion of LOS, additional biomarkers could help the clinician in identifying non-infected patients.

Two new mutations of the CLMP gene identified in a newborn presenting congenital short-bowel syndrome.

Congenital short-bowel syndrome (CSBS) is a rare neonatal pathology associated with poor prognosis and high mortality rate. We describe a newborn presenting CSBS intestinal malrotation and chronic intestinal pseudo-obstruction syndrome (CIPS), compound heterozygous for two previously unreported heterozygous mutations in Coxsackie and adenovirus receptor-like membrane protein (CLMP) gene, one in intron 1 (c.28+1G>C), the other on exon 4 (c502C>T, p.R168X). Both mutations are predicted to be pathogenic, leading to impaired splicing and the appearance of a premature stop codon, respectively. Our case is remarkable in that it concerns two heterozygous truncating mutations associated with a good clinical prognosis with a favorable cerebral and gastrointestinal outcome and a substantial enteral input at 8 months of age, despite a small intestine measuring only 35cm.

Conserved domains and structure prediction of human cytomegalovirus UL27 protein.

BACKGROUND: The human cytomegalovirus (HCMV) nuclear UL27 protein (pUL27) could be involved at the stage of nuclear egress. Maribavir is a new anti-HCMV drug that targets nuclear egress through direct inhibition of the HCMV serine-threonine kinase, UL97 protein (pUL97). Because maribavir-resistance-related mutations are observed in both proteins, pUL27 is thought to interfere with pUL97 activity; however, its mechanism of action remains unclear. METHODS: As there is no available crystal structure for pUL27 or any known structures of its homologous proteins, we attempted to identify pUL27 functional domains by sequence analysis, identification of conserved domains, structure prediction and matching with previously known maribavir resistance mutations. RESULTS: The UL27 sequence analysis of 20 HCMV wild-type strains and 8 ganciclovir-resistant HCMV strains allowed us to describe four conserved domains, to localize the putative phosphorylation sites and to identify protein-protein interface domains, suggesting that pUL27 could interact with either pUL97 or itself. CONCLUSIONS: Although the function of pUL27 is still unknown in the HCMV replication cycle, our approach identified target domains that appeared to be essential to the function of pUL27. This work provides a better understanding on the relative importance of each pUL27 mutation and could form the basis of later comparison analyses, when a three-dimensional structure of a pUL27 homologue will be available.