PDF(Pubmed)
Abstract：
UNASSIGNED: Molecular mechanisms underlying perioperative acute phase reactions in cardiac surgery are largely unknown. We aimed to characterise perioperative alterations of the acute phase plasma proteome in a cohort of adult patients undergoing on-pump cardiac surgery using high-throughput mass spectrometry and to identify candidate proteins potentially relevant to postoperative clinical outcome through a novel, multi-step approach.
UNASSIGNED: This study is an analysis of the Bern Perioperative Biobank, a prospective cohort of adults who underwent cardiac surgery with the use of cardiopulmonary bypass (CPB) at Bern University Hospital between January and December 2019. Blood samples were taken before induction of anaesthesia and on postoperative day one. Proteomic analyses were performed by mass spectrometry. Through a multi-step, exploratory approach, hit-proteins were first identified according to their perioperative prevalence and dynamics. The set of hit-proteins were associated with predefined clinical outcome measures (all-cause one-year mortality, length of hospital stay, postoperative myocardial infarction and stroke until hospital discharge).
UNASSIGNED: 192 patients [75.5% male, median age 67.0 (IQR 60.0-73.0)] undergoing cardiac surgery with the use of CPB were included in this analysis. In total, we identified and quantified 402 proteins across all samples, whereof 30/402 (7%) proteins were identified as hit-proteins. Three hit-proteins-LDHB, VCAM1 and IGFBP2-demonstrated the strongest associations with clinical outcomes. After adjustment both for age, sex, BMI and for multiple comparisons, the scaled preoperative levels of IGFBP2 were associated with 1-year all-cause mortality (OR 10.63; 95% CI: 2.93-64.00; p = 0.046). Additionally, scaled preoperative levels of LDHB (OR 5.58; 95% CI: 2.58-8.57; p = 0.009) and VCAM1 (OR 2.32; 95% CI: 0.88-3.77; p = 0.05) were found to be associated with length of hospital stay.
UNASSIGNED: We identified a subset of promising candidate plasma proteins relevant to outcome after on-pump cardiac surgery. IGFBP2 showed a strong association with clinical outcome measures and a significant association of preoperative levels with 1-year all-cause mortality. Other proteins strongly associated with outcome were LDHB and VCAM1, reflecting the dynamics in the acute phase response, inflammation and myocardial injury. We recommend further investigation of these proteins as potential outcome markers after cardiac surgery.
UNASSIGNED: ClinicalTrials.gov; NCT04767685, data are available via ProteomeXchange with identifier PXD046496.
UNASSIGNED: This study is an analysis of the Bern Perioperative Biobank, a prospective cohort of adults who underwent cardiac surgery with the use of cardiopulmonary bypass (CPB) at Bern University Hospital between January and December 2019. Blood samples were taken before induction of anaesthesia and on postoperative day one. Proteomic analyses were performed by mass spectrometry. Through a multi-step, exploratory approach, hit-proteins were first identified according to their perioperative prevalence and dynamics. The set of hit-proteins were associated with predefined clinical outcome measures (all-cause one-year mortality, length of hospital stay, postoperative myocardial infarction and stroke until hospital discharge).
UNASSIGNED: 192 patients [75.5% male, median age 67.0 (IQR 60.0-73.0)] undergoing cardiac surgery with the use of CPB were included in this analysis. In total, we identified and quantified 402 proteins across all samples, whereof 30/402 (7%) proteins were identified as hit-proteins. Three hit-proteins-LDHB, VCAM1 and IGFBP2-demonstrated the strongest associations with clinical outcomes. After adjustment both for age, sex, BMI and for multiple comparisons, the scaled preoperative levels of IGFBP2 were associated with 1-year all-cause mortality (OR 10.63; 95% CI: 2.93-64.00; p = 0.046). Additionally, scaled preoperative levels of LDHB (OR 5.58; 95% CI: 2.58-8.57; p = 0.009) and VCAM1 (OR 2.32; 95% CI: 0.88-3.77; p = 0.05) were found to be associated with length of hospital stay.
UNASSIGNED: We identified a subset of promising candidate plasma proteins relevant to outcome after on-pump cardiac surgery. IGFBP2 showed a strong association with clinical outcome measures and a significant association of preoperative levels with 1-year all-cause mortality. Other proteins strongly associated with outcome were LDHB and VCAM1, reflecting the dynamics in the acute phase response, inflammation and myocardial injury. We recommend further investigation of these proteins as potential outcome markers after cardiac surgery.
UNASSIGNED: ClinicalTrials.gov; NCT04767685, data are available via ProteomeXchange with identifier PXD046496.
摘要：
■心脏手术围手术期急性期反应的分子机制尚不清楚。我们的目的是使用高通量质谱法描述接受体外循环心脏手术的成年患者的围手术期急性期血浆蛋白质组的变化，并通过一种新的方法鉴定与术后临床结果潜在相关的候选蛋白，多步法。
■这项研究是对伯尔尼围手术期生物样本库的分析，2019年1月至12月在伯尔尼大学医院接受体外循环(CPB)心脏手术的成人前瞻性队列.在麻醉诱导前和术后第一天采集血样。通过质谱进行蛋白质组学分析。通过多步骤，探索性方法，首先根据其围手术期患病率和动态来鉴定命中蛋白.一组命中蛋白与预定义的临床结果指标（全因一年死亡率，住院时间,术后心肌梗死和中风，直至出院）。
■192名患者[75.5%为男性，本分析包括使用CPB进行心脏手术的中位年龄67.0(IQR60.0-73.0)].总的来说,我们在所有样本中鉴定并定量了402种蛋白质，其中30/402(7%)蛋白质被鉴定为命中蛋白。三种命中蛋白-LDHB,VCAM1和IGFBP2与临床结果的相关性最强。在调整了年龄后，性别,BMI和多重比较，IGFBP2的术前分级水平与1年全因死亡率相关(OR10.63;95%CI:2.93-64.00;p=0.046).此外,术前LDHB(OR5.58;95%CI:2.58-8.57;p=0.009)和VCAM1(OR2.32;95%CI:0.88-3.77;p=0.05)水平与住院时间相关.
■我们确定了与泵心脏手术后结果相关的有希望的候选血浆蛋白的子集。IGFBP2显示出与临床结果指标的强关联以及术前水平与1年全因死亡率的显著关联。其他与结果密切相关的蛋白是LDHB和VCAM1，反映了急性期反应的动力学。炎症和心肌损伤。我们建议进一步研究这些蛋白质作为心脏手术后的潜在结果标志物。
■ClinicalTrials.gov;NCT04767685，数据可通过ProteomeXchange获得，标识符为PXD046496。
■这项研究是对伯尔尼围手术期生物样本库的分析，2019年1月至12月在伯尔尼大学医院接受体外循环(CPB)心脏手术的成人前瞻性队列.在麻醉诱导前和术后第一天采集血样。通过质谱进行蛋白质组学分析。通过多步骤，探索性方法，首先根据其围手术期患病率和动态来鉴定命中蛋白.一组命中蛋白与预定义的临床结果指标（全因一年死亡率，住院时间,术后心肌梗死和中风，直至出院）。
■192名患者[75.5%为男性，本分析包括使用CPB进行心脏手术的中位年龄67.0(IQR60.0-73.0)].总的来说,我们在所有样本中鉴定并定量了402种蛋白质，其中30/402(7%)蛋白质被鉴定为命中蛋白。三种命中蛋白-LDHB,VCAM1和IGFBP2与临床结果的相关性最强。在调整了年龄后，性别,BMI和多重比较，IGFBP2的术前分级水平与1年全因死亡率相关(OR10.63;95%CI:2.93-64.00;p=0.046).此外,术前LDHB(OR5.58;95%CI:2.58-8.57;p=0.009)和VCAM1(OR2.32;95%CI:0.88-3.77;p=0.05)水平与住院时间相关.
■我们确定了与泵心脏手术后结果相关的有希望的候选血浆蛋白的子集。IGFBP2显示出与临床结果指标的强关联以及术前水平与1年全因死亡率的显著关联。其他与结果密切相关的蛋白是LDHB和VCAM1，反映了急性期反应的动力学。炎症和心肌损伤。我们建议进一步研究这些蛋白质作为心脏手术后的潜在结果标志物。
■ClinicalTrials.gov;NCT04767685，数据可通过ProteomeXchange获得，标识符为PXD046496。
