Refine
Document Type
- Article (3)
Language
- English (3)
Has Fulltext
- yes (3)
Is part of the Bibliography
- no (3)
Keywords
- - (1)
- Gasdermin D (1)
- LC-MS/MS (1)
- biomarker (1)
- extracellular traps (1)
- human breast milk (1)
- monocytes (1)
- neutrophils (1)
- peptidome (1)
- postoperative cognitive dysfunction (1)
Institute
Publisher
- MDPI (3) (remove)
Advances in spine surgery enable technically safe interventions in older patients with disabling spine disease, yet postoperative delirium (POD) poses a serious risk for postoperative recovery. This study investigates biomarkers of pro-neuroinflammatory states that may help objectively define the pre-operative risk for POD. This study enrolled patients aged ≥60 scheduled for elective spine surgery under general anesthesia. Biomarkers for a pro-neuroinflammatory state included S100 calcium-binding protein β (S100β), brain-derived neurotrophic factor (BDNF), Gasdermin D, and the soluble ectodomain of the triggering receptor expressed on myeloid cells 2 (sTREM2). Postoperative changes of Interleukin-6 (IL-6), Interleukin-1β (IL-1β), and C-reactive protein (CRP) were assessed as markers of systemic inflammation preoperatively, intraoperatively, and early postoperatively (up to 48 h). Patients with POD (n = 19, 75.7 ± 5.8 years) had higher pre-operative levels of sTREM2 (128.2 ± 69.4 pg/mL vs. 97.2 ± 52.0 pg/mL, p = 0.049) and Gasdermin D (2.9 ± 1.6 pg/mL vs. 2.1 ± 1.4 pg/mL, p = 0.29) than those without POD (n = 25, 75.6 ± 5.1 years). STREM2 was additionally a predictor for POD (OR = 1.01/(pg/mL) [1.00–1.03], p = 0.05), moderated by IL-6 (Wald-χ2 = 4.06, p = 0.04). Patients with POD additionally showed a significant increase in IL-6, IL-1β, and S100β levels on the first postoperative day. This study identified higher levels of sTREM2 and Gasdermin D as potential markers of a pro-neuroinflammatory state that predisposes to the development of POD. Future studies should confirm these results in a larger cohort and determine their potential as an objective biomarker to inform delirium prevention strategies.
The release of DNA by cells during extracellular trap (ET) formation is a defense function of neutrophils and monocytes. Neutrophil ET (NET) formation in term infants is reduced compared to adults. Objective: The aim was to quantify NET and monocyte ET (MET) release and the respective key enzymes myeloperoxidase (MPO) and neutrophil elastase (NE) in preterm infants. In this prospective explorative study, ET induction was stimulated by N-formylmethionine-leucyl-phenylalanine (fMLP), phorbol 12-myristate 13-acetate (PMA), lipopolysaccharide (LPS), and lipoteichoic acid (LTA) in the cord blood of preterm infants (n = 55, 23–36 weeks) compared to term infants and adults. METs were quantified by microscopy, and NETs by microscopy and flow cytometry. We also determined the MPO levels within NETs and the intracellular concentrations of NE and MPO in neutrophils. The percentage of neutrophils releasing ET was significantly reduced for preterm infants compared to adults for all stimulants, and with a 68% further reduction for PMA compared to term infants (p = 0.0141). The NET area was not reduced except for when fMLP was administered. The amount of MPO in NET-producing cells was reduced in preterm infants compared to term infants. For preterm infants, but not term infants, the percentage of monocytes releasing ETs was significantly reduced compared to healthy adults for LTA and LPS stimulation. Conclusion: In preterm infants, ETs are measurable parts of the innate immune system, but are released in a reduced percentage of cells compared to adults.
Human donor milk (HDM) provides appropriate nutrition and offers protective functionsin preterm infants. The aim of the study is to examine the impact of different storage conditions onthe stability of the human breast milk peptidome. HDM was directly frozen at−80◦C or stored at−20◦C (120 h), 4◦C (6 h), or room temperature (RT for 6 or 24 h). The milk peptidome was profiledby mass spectrometry after peptide collection by ultrafiltration. Profiling of the peptidome covered3587 peptides corresponding to 212 proteins. The variance of the peptidome increased with storagetemperature and time and varied for different peptides. The highest impact was observed whensamples were stored at RT. Smaller but significant effects were still observed in samples stored at4◦C, while samples showed highest similarity to those immediately frozen at−80◦C when storedat−20◦C. Peptide structures after storage at RT for 24 h point to the increased activity of thrombinand other proteases cleaving proteins at lysine/arginine. The results point to an ongoing proteindegradation/peptide production by milk-derived proteases. They underline the need for immediatefreezing of HDM at−20◦C or−80◦C to prevent degradation of peptides and enable reproducibleinvestigation of prospectively collected samples.