Mankowski Robert T, Anton Stephen D, Ghita Gabriela L, Brumback Babette, Darden Dijoia B, Bihorac Azra, Leeuwenburgh Christiaan, Moldawer Lyle L, Efron Philip A, Brakenridge Scott C, Moore Frederick A
Department of Aging and Geriatric Research, University of Florida, Gainesville, USA.
Department of Neprhology, University of Florida, Gainesville, USA.
J Gerontol A Biol Sci Med Sci. 2022 Jan 7;77(1):188-196. doi: 10.1093/gerona/glab080.
Hospital deaths after sepsis have decreased substantially and most young adult survivors rapidly recover (RAP). However, many older survivors develop chronic critical illness (CCI) with poor long-term outcomes. The etiology of CCI is multifactorial and the relative importance remains unclear. Sepsis is caused by a dysregulated immune response and biomarkers reflecting a persistent inflammation, immunosuppression, and catabolism syndrome (PICS) have been observed in CCI after sepsis. Therefore, the purpose of this study was to compare serial PICS biomarkers in (i) older (vs young) adults and (ii) older CCI (vs older RAP) patients to gain insight into underlying pathobiology of CCI in older adults.
Prospective longitudinal study with young (≤45 years) and older (≥65 years) septic adults, who were characterized by (i) baseline predisposition, (ii) hospital outcomes, (iii) serial Sequential Organ Failure Assessment (SOFA) organ dysfunction scores over 14 days, (iv) Zubrod Performance status at 3-, 6-, and 12-month follow-up, and (v) mortality over 12 months, was conducted. Serial blood samples over 14 days were analyzed for selected biomarkers reflecting PICS.
Compared to the young, more older adults developed CCI (20% vs 42%) and had markedly worse serial SOFA scores, performance status, and mortality over 12 months. Additionally, older (vs young) and older CCI (vs older RAP) patients had more persistent aberrations in biomarkers reflecting inflammation, immunosuppression, stress metabolism, lack of anabolism, and antiangiogenesis over 14 days after sepsis.
Older (vs young) and older CCI (vs older RAP) patient subgroups demonstrate early biomarker evidence of the underlying pathobiology of PICS.
脓毒症后的医院死亡率已大幅下降，大多数年轻成年幸存者能迅速康复（RAP）。然而，许多老年幸存者会发展为慢性危重病（CCI），长期预后较差。CCI的病因是多因素的，其相对重要性尚不清楚。脓毒症由免疫反应失调引起，在脓毒症后的CCI中已观察到反映持续炎症、免疫抑制和分解代谢综合征（PICS）的生物标志物。因此，本研究的目的是比较（i）老年人（与年轻人相比）和（ii）老年CCI患者（与老年RAP患者相比）的系列PICS生物标志物，以深入了解老年患者CCI的潜在病理生物学机制。
对年轻（≤45岁）和老年（≥65岁）脓毒症成人进行前瞻性纵向研究，这些患者的特征包括（i）基线易感性，（ii）医院结局，（iii）14天内的系列序贯器官衰竭评估（SOFA）器官功能障碍评分，（iv）3个月、6个月和12个月随访时的Zubrod体能状态，以及（v）12个月内的死亡率。分析14天内的系列血样以检测反映PICS的选定生物标志物。
与年轻人相比，更多老年成人发展为CCI（20%对42%），且12个月内的系列SOFA评分、体能状态和死亡率明显更差。此外，老年（与年轻相比）和老年CCI患者（与老年RAP患者相比）在脓毒症后14天内，反映炎症、免疫抑制、应激代谢、合成代谢缺乏和抗血管生成的生物标志物存在更持续的异常。
老年（与年轻相比）和老年CCI（与老年RAP相比）患者亚组显示出PICS潜在病理生物学机制的早期生物标志物证据。
