Background. Neonatal septicemia is a critical medical situation; current conventional laboratory methods still have many limitations and diagnostic obstacles. For this purpose, last decades have witnessed a challenge between the battery of sepsis biomarkers including many leukocyte surface antigens, not only for early diagnostic purposes but also for better follow-up and good management of sepsis patients. Aim. To evaluate the diagnostic, prognostic, and monitoring performance of both neutrophil CD64 (nCD64) and presepsin as sepsis biomarkers compared to each other and to the conventional laboratory sepsis parameters aiming to decide which is the best fitting for routine daily use in neonatal intensive care units (NICUs). Methods. 235 neonates were enrolled from three Egyptian neonatal ICUs, during the period from November 2015 till March 2018; they were classified into two main groups: the control group (n = 102) and the sepsis group (n = 133). Laboratory sepsis evaluation included highly sensitive CRP (hs-CRP), CBC, in addition to nCD64 (flow cytometry technique), and presepsin measurement (CLEIA technique combined with Magtration® technology); the diagnosis was confirmed thereafter by positive blood culture results (BacT/Alert system). Sixty-two of the enrolled sepsis neonates were subjected to follow-up assessment; they were reclassified according to their clinical improvement at the second time assessment into (group 1: sepsis group without improvement) (n = 20) and (group 2: improved sepsis group) (n = 42). Results. Significant increase in nCD64 and presepsin values was found in sepsis groups compared to the controls. At cutoff 41.6%, nCD64% could discriminate the presence of septicemia with sensitivity 94.7%, specificity 93.6 %, and AUC 0.925, while presepsin at cutoff 686 pg/ml achieves sensitivity 82.7%, specificity 95.5%, and AUC 0.887, respectively. Significant increase in nCD64 ( P < 0.001 ) and hs-CRP ( P = 0.018 ) values was observed in severe sepsis/septic shock patients compared to nonsevere sepsis patients. Delta change percentage (dC%) between initial and follow-up evaluations for both improved and nonimproved sepsis patients was dC Z value −5.904 for nCD64% followed by dC Z value −4.494 for presepsin. Conclusion. nCD64 and presepsin are valuable early diagnostic and monitoring sepsis biomarkers; the highest sensitivity could be achieved by a univariant sepsis marker in this study was recorded by the nCD64% biomarker, while the highest specificity was documented by presepsin. Combined measurement of both achieves the highest diagnostic performance in sepsis neonates. Either of CD64 or presepsin combined with hs-CRP associated with better performance than any of them alone. nCD64 carries an additional promising role in reflecting sepsis prognosis.

Background. Neonatal sepsis (NS) is a very critical medical situation associated with high morbidities and mortalities. There is an utmost need for a new tool helping in early diagnosis and proper management of sepsis neonates. Neutrophil CD64 (nCD64) shows a very promising value in this concerning issue. Aim. Evaluate the diagnostic, monitoring, and prognostic performances of nCD64 and highly sensitive CRP (hs-CRP) in NS as well as the possible best panel of biomarkers that can achieve the most desirable results. Methods. Patients were enrolled from three neonatal intensive care units (NICUs) (n=121 patients) and classified according to their initial sepsis evaluation into three groups: disease control group (n=30), proven sepsis group (n=17), and clinical sepsis group (n=74). Laboratory evaluation included hs-CRP, complete blood count (CBC), and blood culture in addition to nCD64 (done by flow cytometry technique). Besides the diagnostic evaluations, follow-up evaluations were done for 40 patients after five days from the first time; patients were reclassified according to their outcome into the improved sepsis neonates’ group (n=26) and sepsis neonates without improvement (n=14). Results. Significant increase in nCD64 and hs-CRP results were present in sepsis groups compared to the disease controls (P<0.001); nCD64 at 43% cutoff value could detect the presence of sepsis with 85.6% sensitivity and 93% specificity. Additionally, delta change percentage (dC%) between improved sepsis neonates and sepsis neonates without improvement showed a significant difference in the levels of both nCD64 (P<0.001) and hs-CRP (P=0.001). Conclusion. Besides the promising diagnostic performance documented by nCD64 which is higher than the other laboratory sepsis biomarkers used routinely in NICUs, nCD64 has a valuable role in sepsis patients’ monitoring and prognostic evaluation. hs-CRP was moderate in its diagnostic and monitoring results being less than that achieved by nCD64. Combined measurement of nCD64% and hs-CRP gives better diagnostic and monitoring performance than that achieved by any of them alone.

The VDR gene Fok I (rs2228570) polymorphism confers susceptibility to CAP in Egyptian children.

Background Pneumonia is the foremost cause of child death worldwide. M‐ficolin is encoded by the FCN1 gene and represents a novel link between innate and adaptive immunity. Objectives To investigate the FCN1 −144 C/A (rs10117466) polymorphism as a potential marker for pneumonia severity and adverse outcome namely complications or mortality in the under‐five Egyptian children. Methods This was a prospective multicenter study that included 620 children hospitalized with World Health Organization‐defined severe pneumonia and 620 matched healthy control children. Polymorphism rs10117466 of the FCN1 gene promoter was analyzed by PCR‐SSP, while serum M‐ficolin levels were assessed by ELISA. Results The FCN1 A/A genotype and A allele at the −144 position were more frequently observed in patients compared to the control children (43.4% vs 27.6%; odds ratio [OR]: 1.62; [95% confidence interval {CI}: 1.18‐2.2]; for the A/A genotype) and (60.8% vs 52.5%; OR: 1.4; [95% CI: 1.19‐1.65]; for the A allele); P < .01. The FCN1 −144 A/A homozygous patients had significantly higher serum M‐ficolin concentrations (mean: 1844 ± 396 ng/mL) compared with those carrying the C/C or C/A genotype (mean: 857 ± 278 and 1073 ± 323 ng/mL, respectively; P = .002). FCN1 −144 A/A genotype was an independent risk factor for adverse outcomes in children with severe pneumonia (adjusted OR = 4.85, [95% CI: 2.96‐10.25]; P = .01). Conclusion The FCN1 A/A genotype at the −144 position was associated with high M‐ficolin serum levels and possibly contributes to enhanced inflammatory response resulting in the adverse outcome of pneumonia in the under‐five Egyptian children.

Background Acute lower respiratory infection (ALRI) is the leading cause of child mortality, especially in the developing world. Polymorphisms in the interleukin 4 (IL‐4) gene have been linked to a variety of human diseases. Objectives To investigate whether the IL‐4 ‐590C/T (rs2243250) polymorphism could be a genetic marker for susceptibility to ALRIs in young Egyptian children. Methods This was a multicenter study conducted on 480 children diagnosed with pneumonia or bronchiolitis, and 480 well‐matched healthy control children. Using PCR‐RFLP analysis, we genotyped a ‐590C/T (rs2243250) single nucleotide polymorphism of the IL‐4 gene promoter, meanwhile the serum IL‐4concentration was measured by ELISA. Results The frequency of the IL‐4 ‐590 T/T genotype and T allele were overrepresented in patients with ALRIs in comparison to the control group (OR = 2.0; [95% confidence interval [CI]: 1.38‐2.96]; for the T/T genotype) and (OR: 1.3; [95%CI: 1.07‐1.56]; for the T allele; P < 0.01). The IL‐4 ‐590 T/T genotype was associated with significantly higher mean serum IL‐4 concentration (58.7 ± 13.4 pg/mL) compared to the C/T genotype (47.6 ± 11 pg/mL) and the C/C genotype (34.8 ± 9.6 pg/mL); P < 0.01. Conclusion The IL‐4 −590C/T (rs2243250) polymorphism may contribute to susceptibility to ALRIs in young Egyptian children.