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. 2021 Jan 6:8:593926.
doi: 10.3389/fped.2020.593926. eCollection 2020.

Cardiac and Inflammatory Necrotizing Enterocolitis in Newborns Are Not the Same Entity

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Cardiac and Inflammatory Necrotizing Enterocolitis in Newborns Are Not the Same Entity

Michaela Klinke et al. Front Pediatr. .

Abstract

Background: Necrotizing enterocolitis (NEC) is an often-fatal neonatal disease involving intestinal hyperinflammation leading to necrosis. Despite ongoing research, (1) conflicting results and (2) comorbidities of NEC patients make early NEC detection challenging and may complicate therapy development. Most research suggests that NEC pathogenesis is multifactorial, involving a combination of (1) gut prematurity; (2) abnormal bacterial colonization; and (3) ischemia-reperfusion (I/R) injury. As neutrophil extracellular traps (NETs) partially mediate I/R injury and drive inflammation in NEC, we hypothesized that NETs contribute to NEC development; particularly in cardiac patients VSports手机版. Methods: A retrospective analysis of baseline characteristics, clinical signs, laboratory parameters, and imaging was conducted for surgically verified NEC cases over 10 years. Patients were stratified into two groups: (1) prior medically or surgically treated cardiac disease (cardiac NEC) and (2) no cardiac comorbidities (inflammatory NEC). Additionally, histology was reassessed for neutrophil activation and NETs formation. Results: A total of 110 patients (cNEC 43/110 vs. iNEC 67/110) were included in the study, with cNEC neonates being significantly older than iNEC neonates (p = 0. 005). While no significant differences were found regarding clinical signs and imaging, laboratory parameters revealed that cNEC patients have significantly increased leucocyte (p = 0. 024) and neutrophil (p < 0. 001) counts. Both groups also differed in pH value (p = 0. 011). Regarding histology: a non-significant increase in staining of myeloperoxidase within the cNEC group could be found in comparison to iNEC samples. Neutrophil elastase (p = 0. 012) and citrullinated histone H3 stained (p = 0. 041) slides showed a significant markup for neonates diagnosed with cNEC in comparison to neonates with iNEC. Conclusion: The study shows that many standardized methods for diagnosing NEC are rather unspecific. However, differing leucocyte and neutrophil concentrations for iNEC and cNEC may indicate a different pathogenesis and may aid in diagnosis. As we propose that iNEC is grounded rather in sepsis and neutropenia, while cNEC primarily involves I/R injuries, which involves neutrophilia and NETs formation, it is plausible that I/R injury due to interventions for cardiac comorbidities results in pronounced neutrophil activation followed by a hyperinflammation reaction and NEC. However, prospective studies are necessary to validate these findings and to determine the accuracy of the potential diagnostic parameters. .

Keywords: NEC; NETs; cardiology; necrotizing enterocolitis; neonates; neutrophil extracellular traps V体育安卓版. .

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Figures

Figure 1
Figure 1
(A) Time from birth until NEC operation: neonates with retrospectively diagnosed iNEC were operated on significantly earlier than patients in the cNEC group. (B) Time from PDA closure until NEC operation: there are no differences between time of surgically confirmed NEC diagnosis and method of PDA closure. Risk of NEC manifestation is highest in the first 2 weeks of PDA closure.
Figure 2
Figure 2
(A) Significantly increased leucocyte concentrations can be found in the cNEC group in comparison to the iNEC group prior to NEC surgery. (B) Neonates with cNEC demonstrate significantly increased neutrophil concentrations prior to confirmative NEC surgery in comparison to iNEC neonates.
Figure 3
Figure 3
(A) Neonates in the cNEC group exhibit significantly decreased BGA pH values in comparison to patients in the iNEC group before NEC surgery has taken place. (B) No significant differences in BGA lactate levels prior to NEC surgery are found between NEC patients when stratified into cNEC and iNEC groups.
Figure 4
Figure 4
(A) No significant differences were found between the cNEC and iNEC groups with regards to MPO immunohistochemical staining and scoring of the affected intestine. (B,C) Neonates with cNEC demonstrate significantly increased NE and H3cit expression as analyzed through immunohistochemical staining of the NEC intestine in comparison to iNEC neonates. All images depicted are visualized using a magnification setting of 10x.

References

    1. Flahive C, Schlegel A, Mezoff EA. Necrotizing enterocolitis: updates on morbidity and mortality outcomes. J Pediatr. (2020) 220:7–9. 10.1016/j.jpeds.2019.12.035 - DOI - PubMed
    1. Neu J, Walker WA. Necrotizing enterocolitis. N Engl J Med. (2011) 364:255–64. 10.1056/NEJMra1005408 - DOI - PMC - PubMed
    1. Alsaied A, Islam N, Thalib L. Global incidence of necrotizing enterocolitis: a systematic review and meta-analysis. BMC Pediatr. (2020) 20:344. 10.1186/s12887-020-02231-5 - DOI - PMC - PubMed
    1. Cognata A, Kataria-Hale J, Griffiths P, Maskatia S, Rios D, O'Donnell A, et al. . Human milk use in the preoperative period is associated with a lower risk for necrotizing enterocolitis in neonates with complex congenital heart disease. J Pediatr. (2019) 215:11–16 e2. 10.1016/j.jpeds.2019.08.009 - DOI - PMC - PubMed
    1. Frost BL, Modi BP, Jaksic T, Caplan MS. New medical and surgical insights into neonatal necrotizing enterocolitis: a review. JAMA Pediatr. (2017) 171:83–8. 10.1001/jamapediatrics.2016.2708 - DOI - PubMed

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