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 concensus. 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. IL-6 was the most commonly identified biomarker. 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.

中文翻译：

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蛋白质组学发现临床谵妄生物标志物：主要研究的系统评价

谵妄是一项重大的医疗保健负担，每年有超过 200 万美国老年人被诊断出谵妄。在外科人群中，谵妄仍然是老年患者最常见的并发症，并且与住院时间更长、护理成本更高、死亡率增加和功能障碍有关。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。尽管最近对谵妄研究产生了兴趣，但它的生物标志物发现仍然是新的。大多数发现生物标志物的尝试都是有针对性的研究，旨在评估一个或多个重点候选人小组中的一个或多个成员在谵妄中的参与。为了更公正的系统生物学观点，我们从 MEDLINE、Cochrane Central、Web of Science、SCOPUS 和 Dimensions 在 2016 年至 2021 年间，用于针对人类老年受试者进行的谵妄生物标志物的非靶向蛋白质组学发现研究。两名审稿人对所有检索结果进行了独立审阅，并以协商一致的方式解决了不一致的问题。从对 1172 篇出版物的总体搜索中，八项经过同行评审的研究符合我们定义的纳入标准。这些报告中确定的 370 种独特的围手术期生物标志物富含涉及免疫系统激活、炎症反应和凝血级联反应的途径。IL-6 是最常见的生物标志物。通过回顾这些研究中候选蛋白质生物标志物的分布，我们得出结论，一组蛋白质，而不是单一的生物标志物，可以区分谵妄病例和非病例。