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维生素D水平、富含γ-羧基谷氨酸蛋白(GRP)和基质γ-羧基谷氨酸蛋白(MGP)以及炎症标志物在预测重症监护患者死亡率中的作用:一种新的生物标志物联系?

The Roles of Vitamin D Levels, Gla-Rich Protein (GRP) and Matrix Gla Protein (MGP), and Inflammatory Markers in Predicting Mortality in Intensive Care Patients: A New Biomarker Link?

作者信息

Seğmen Fatih, Aydemir Semih, Küçük Onur, Dokuyucu Recep

机构信息

Department of Intensive Care Unit, Ankara City Hospital, Ankara 06800, Turkey.

Department of Anesthesiology and Reanimation, Yenimahalle Training and Research Hospital, University of Yıldırım Beyazit, Ankara 06800, Turkey.

出版信息

Metabolites. 2024 Nov 13;14(11):620. doi: 10.3390/metabo14110620.

DOI:10.3390/metabo14110620
PMID:39590856
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11596285/
Abstract

OBJECTIVES

Identifying reliable biomarkers to predict mortality in critically ill patients is crucial for optimizing management in intensive care units (ICUs). Inflammatory and metabolic markers are increasingly recognized for their prognostic value. This study aims to evaluate the association of various inflammatory and metabolic markers with ICU mortality.

METHODS

This prospective observational study was conducted from January 2023 to January 2024 in the City Hospital's ICU. A total of 160 critically ill patients were enrolled. Laboratory parameters, including white blood cell (WBC) count, red cell distribution width (RDW), platelet count, neutrophil count, mean platelet volume (MPV), monocyte count, lymphocyte count, procalcitonin (PCT), C-reactive protein (CRP), calcium (Ca), and vitamin D levels, were analyzed. Additionally, ratios such as the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), systemic inflammatory index (SII), and pan-immune-inflammation value (PIV) were calculated. Plasma levels of Gla-rich protein (GRP) and dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP) were measured using ELISA.

RESULTS

The mean age of the patients included in the study was 60.5 ± 15.8 years. Cardiovascular disease was present in 72 patients (45%), respiratory system disease in 58 (36%), and chronic kidney disease (CKD) in 38 (24%). Additionally, 61 patients (38%) had diabetes, and 68 (42%) had hypertension. Inflammatory markers, including PLR, NLR, and PIV, were all significantly higher in non-survivors, while calcium and vitamin D levels were lower ( < 0.05). Higher WBC, RDW, neutrophil count, PLR, NLR, PIV, CRP, procalcitonin, GRP, and dp-ucMGP levels were positively correlated with longer hospital stays and increased mortality. In contrast, platelet and lymphocyte counts were negatively correlated with both outcomes ( < 0.05). Vitamin D levels showed an inverse relationship with both hospital stay and mortality, indicating that lower levels were associated with worse outcomes ( < 0.05). In multiple logistic regression analysis, elevated WBC count (OR = 1.20, = 0.02), RDW (OR = 1.35, = 0.01), neutrophil count (OR = 1.25, = 0.01), MPV (OR = 1.20, = 0.02), PLR (OR = 1.30, = 0.01), NLR (OR = 1.40, = 0.001), PIV (OR = 1.50, = 0.001), CRP (OR = 1.32, = 0.01), procalcitonin (OR = 1.45, = 0.001), GRP (OR = 1.40, = 0.001), and dp-ucMGP (OR = 1.30, = 0.001) levels were significantly associated with increased mortality.

CONCLUSIONS

Inflammatory and metabolic markers, particularly NLR, PLR, PIV, GRP, and dp-ucMGP, are strong predictors of mortality in ICU patients. These markers provide valuable insights for risk stratification and early identification of high-risk patients, potentially guiding more targeted interventions to improve outcomes.

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b5f/11596285/404e73348085/metabolites-14-00620-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b5f/11596285/c9a99cdafd47/metabolites-14-00620-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b5f/11596285/404e73348085/metabolites-14-00620-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b5f/11596285/c9a99cdafd47/metabolites-14-00620-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b5f/11596285/404e73348085/metabolites-14-00620-g002.jpg
摘要

目的

识别可靠的生物标志物以预测重症患者的死亡率对于优化重症监护病房(ICU)的管理至关重要。炎症和代谢标志物因其预后价值而越来越受到认可。本研究旨在评估各种炎症和代谢标志物与ICU死亡率之间的关联。

方法

本前瞻性观察性研究于2023年1月至2024年1月在市医院ICU进行。共纳入160例重症患者。分析了实验室参数,包括白细胞(WBC)计数、红细胞分布宽度(RDW)、血小板计数、中性粒细胞计数、平均血小板体积(MPV)、单核细胞计数、淋巴细胞计数、降钙素原(PCT)、C反应蛋白(CRP)、钙(Ca)和维生素D水平。此外,还计算了血小板与淋巴细胞比值(PLR)、中性粒细胞与淋巴细胞比值(NLR)、全身炎症指数(SII)和全免疫炎症值(PIV)等比值。采用酶联免疫吸附测定法(ELISA)测量富含γ-羧基谷氨酸蛋白(GRP)和去磷酸化未羧化基质γ-羧基谷氨酸蛋白(dp-ucMGP)的血浆水平。

结果

纳入研究的患者平均年龄为60.5±15.8岁。72例(45%)患者患有心血管疾病,58例(36%)患有呼吸系统疾病,38例(24%)患有慢性肾脏病(CKD)。此外,61例(38%)患者患有糖尿病,68例(42%)患者患有高血压。包括PLR、NLR和PIV在内的炎症标志物在非存活者中均显著升高,而钙和维生素D水平较低(P<0.05)。较高的WBC、RDW、中性粒细胞计数、PLR、NLR、PIV、CRP、降钙素原、GRP和dp-ucMGP水平与更长的住院时间和更高的死亡率呈正相关。相比之下,血小板和淋巴细胞计数与这两个结果均呈负相关(P<0.05)。维生素D水平与住院时间和死亡率均呈负相关,表明较低水平与更差的预后相关(P<0.05)。在多因素logistic回归分析中,WBC计数升高(OR = 1.20,P = 0.02)、RDW(OR = 1.35,P = 0.01)、中性粒细胞计数(OR = 1.25,P = 0.01)、MPV(OR = 1.20,P = 0.02)、PLR(OR = 1.30,P = 0.01)、NLR(OR = 1.40,P = 0.001)、PIV(OR = 1.50,P = 0.001)、CRP(OR = 1.32,P = 0.01)、降钙素原(OR = 1.45,P = 0.001)、GRP(OR = 1.40,P = 0.001)和dp-ucMGP(OR = 1.30,P = 0.001)水平与死亡率增加显著相关。

结论

炎症和代谢标志物,特别是NLR、PLR、PIV、GRP和dp-ucMGP,是ICU患者死亡率的强预测指标。这些标志物为风险分层和高危患者的早期识别提供了有价值的见解,可能有助于指导更有针对性的干预措施以改善预后。

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