Academic Journal
Postoperative Innate Immune Dysregulation, Proteomic, and Monocyte Epigenomic Changes After Colorectal Surgery: A Substudy of a Randomized Controlled Trial.
| العنوان: | Postoperative Innate Immune Dysregulation, Proteomic, and Monocyte Epigenomic Changes After Colorectal Surgery: A Substudy of a Randomized Controlled Trial. |
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| المؤلفون: | Albers-Warlé, K.I., Helder, L.S., Groh, L.A., Polat, F., Panhuizen, I.F., Snoeck, M.M.J., Kox, M., Eijk, L.T.G.J. van, Joosten, L.A.B., Netea, M.G., Negishi, Y., Mhlanga, M., Keijzer, C., Scheffer, G.J., Warlé, M.C. |
| المصدر: | Anesthesia and Analgesia, 140, 1, pp. 185-196 |
| سنة النشر: | 2025 |
| المجموعة: | Radboud University: DSpace |
| مصطلحات موضوعية: | Anesthesiology - Radboud University Medical Center, Intensive Care - Radboud University Medical Center, Internal Medicine - Radboud University Medical Center, Operating Rooms - Radboud University Medical Center, Surgery - Radboud University Medical Center |
| الوصف: | Item does not contain fulltext ; BACKGROUND: Colorectal surgery is associated with moderate-to-severe postoperative complications in over 25% of patients, predominantly infections. Monocyte epigenetic alterations leading to immune tolerance could explain postoperative increased susceptibility to infections. This research explores whether changes in monocyte DNA accessibility contribute to postoperative innate immune dysregulation. METHODS: Damage-associated molecular patterns (DAMPs) and ex vivo cytokine production capacity were measured in a randomized controlled trial (n = 100) in colorectal surgery patients, with additional exploratory subgroup proteomic (proximity extension assay; Olink) and epigenomic analyses (Assay for Transposase-Accessible Chromatin [ATAC sequencing]). Monocytes of healthy volunteers were used to study the effect of high-mobility group box 1 (HMGB1) and heat shock protein 70 (HSP70) on cytokine production capacity in vitro. RESULTS: Plasma DAMPs were increased after surgery. HMGB1 showed a mean 235% increase from before- (preop) to the end of surgery (95% confidence interval [CI] [166 - 305], P < .0001) and 90% increase (95% CI [63-118], P = .0004) preop to postoperative day 1 (POD1). HSP70 increased by a mean 12% from preop to the end of surgery (95% CI [3-21], not significant) and 30% to POD1 (95% CI [18-41], P < .0001). Nuclear deoxyribonucleic acid (nDNA) increases by 66% (95% CI [40-92], P < .0001) at the end of surgery and 94% on POD1 (95% CI [60-127], P < .0001). Mitochondrial DNA (mtDNA) increases by 370% at the end of surgery (95% CI [225-515], P < .0001) and by 503% on POD1 (95% CI [332-673], P < .0001). In vitro incubation of monocytes with HSP70 decreased cytokine production capacity of tumor necrosis factor (TNF) by 46% (95% CI [29-64], P < .0001), IL-6 by 22% (95% CI [12-32], P = .0004) and IL-10 by 19% (95% CI [12-26], P = .0015). In vitro incubation with HMGB1 decreased cytokine production capacity of TNF by 34% (95% CI [3-65], P = .0003), ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| Relation: | https://hdl.handle.net/2066/314656 |
| DOI: | 10.1213/ANE.0000000000007297 |
| الاتاحة: | https://hdl.handle.net/2066/314656 https://doi.org/10.1213/ANE.0000000000007297 |
| رقم الانضمام: | edsbas.41044342 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1213/ANE.0000000000007297 |
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