Proteomics for the Discovery of Clinical Delirium Biomarkers: A Systematic Review of Major Studies.
Proteomics for the Discovery of Clinical Delirium Biomarkers: A Systematic Review of Major Studies.
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DOI：
10.1213/ane.0000000000006246
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发表时间：
2023-03-01
影响因子：
5.7
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中科院分区：
文献类型：
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精神错乱是一种重大的医疗负担，每年有200多万美国老年人被诊断为精神错乱。在外科人群中，精神错乱仍然是老年患者最常见的并发症，并与住院时间更长、护理成本更高、死亡率增加和功能障碍有关。目前对疾病的发病机制知之甚少，目前的诊断方法有些主观和武断，目前缺乏明确的诊断生物标志物。尽管最近人们对精神错乱的研究感兴趣，但对它的生物标记物的发现仍然是新的。大多数发现生物标记物的尝试都是有针对性的研究，试图评估一个集中的候选人小组中的一个或多个成员是否参与了精神错乱。为了获得更公正的系统生物学观点，我们搜索了2016至2021年间MEDLINE、Cochrane Central、Web of Science、Scope us和Dimensions的文献，以寻找在人类老年受试者身上进行的关于精神错乱生物标记物的无针对性蛋白质组发现研究。两名审查员对所有搜索结果进行了独立审查，并以协商一致的方式解决了不一致问题。从对1172种出版物的总体搜索中，8项同行评议的研究符合我们定义的纳入标准。这些报告中确定的370个独特的围手术期生物标志物在涉及免疫系统激活、炎症反应和凝血级联反应的途径中丰富。最常见的生物标志物是IL-6。通过回顾这些研究的候选蛋白质生物标记物的分布，我们得出结论，一组蛋白质，而不是单一的生物标记物，将允许区分精神错乱病例和非病例。在同行评议的文献中，缺乏假说生成的研究也表明，对精神错乱病理机制的系统生物学观点尚未完全出现。
Delirium represents a significant healthcare burden, diagnosed in over two million elderly Americans each year. In the surgical population, delirium remains the most common complication among elderly patients and is associated with longer hospital stays, higher costs of care, increased mortality and functional impairment. The pathomechanism of disease is poorly understood, with current diagnostic approaches somewhat subjective and arbitrary, and definitive diagnostic biomarkers are currently lacking. Despite the recent interest in delirium research, biomarker discovery for it remains new. Most attempts to discover biomarkers are targeted studies that seek to assess the involvement of one or more members of a focused panel of candidates in delirium. For a more unbiased, systems-biology view, we searched literature from MEDLINE, Cochrane Central, Web of Science, SCOPUS, and Dimensions between 2016 and 2021 for untargeted proteomic discovery studies for biomarkers of delirium conducted on human geriatric subjects. Two reviewers conducted independent review of all search results and resolved discordance by consensus. From an overall search of 1172 publications, eight peer-reviewed studies met our defined inclusion criteria. The 370 unique peri-operative biomarkers identified in these reports are enriched in pathways involving the activation of the immune system, inflammatory response, and the coagulation cascade. The most frequently identified biomarker was IL-6. By reviewing the distribution of protein biomarker candidates from these studies, we conclude that a panel of proteins, rather than a single biomarker, would allow for discriminating delirium cases from non-cases. The paucity of hypothesis-generating studies in the peer-reviewed literature also suggests that a systems-biology view of delirium pathomechanisms has yet to fully emerge.