Data_Sheet_1_Development and validation of clinical criteria for critical illness-associated immune dysfunction: based on the MIMIC-IV database.docx

BackgroundCritical illness-associated immune dysfunction (CIID) is prevalent in the ICU and frequently resulted in uncontrollably immune responses. Critical immunological dysfunction is understood to be important, although there are currently no clinically accepted diagnostic criteria for it. Given this, we examined the literature and developed an initial diagnostic criterion that we validated using the MIMIC-IV database.
MethodsWe searched the related literature in the last 32 years. Patients admitted to the ICU for the first time were selected by screening the MIMIC-IV database. Different criteria were used to categorize patients into groups related to immune dysfunction (ID) and non-immune dysfunction (NID). Within the ID group, patients were subdivided into three subgroups: hyperinflammatory (HI), immunosuppression (IS), and a subgroup combining immunosuppression and hyperinflammation (HI+IS). The APACHE II was used to measure the patients’ severity. The association between immune dysfunction and mortality after 30 or 180 days was evaluated through the KM curves and COX regression analysis.
ResultsBy summarizing relevant literature, we proposed the initial diagnostic criteria. The analysis included 43,965 patients, with approximately 77% meeting the diagnostic criteria for CIID. We observed that patients with immune dysfunction possessed higher APACHE II scores and there were differences in peak APACHE II among the three subgroups. When comparing patients’ 30-day mortality in the COX model, it is evident that patients in the IS subgroup had the lowest risk and patients in the HI subgroup the greatest risk after accounting for all covariates. In contrast, patients in the IS subgroup had the highest risk of death, those in the HI subgroup had the lowest risk when comparing long-term mortality. In summary, we propose and validate diagnostic criteria related to CIID. Subgroup analyses were carried out, which also revealed variations between the three groups.
ConclusionThe diagnostic criteria were confirmed by the MIMIC-IV database, demonstrating the diagnostic criteria were scientifically valid and reliable.

背景 重症疾病相关性免疫功能障碍（Critical illness-associated immune dysfunction, CIID）在重症监护病房（Intensive Care Unit, ICU）中高发，常引发失控的免疫应答。尽管目前尚无临床公认的诊断标准，但重症免疫功能障碍被认为具有重要临床意义。鉴于此，本研究梳理相关文献并制定了初步诊断标准，且利用MIMIC-IV数据库对该标准进行了验证。

方法 本研究系统检索并梳理了近32年的相关文献。通过筛选MIMIC-IV数据库，纳入首次入住重症监护病房的患者。采用不同标准将患者分为免疫功能障碍（Immune Dysfunction, ID）组与非免疫功能障碍（Non-immune Dysfunction, NID）组。其中，ID组患者进一步被划分为三个亚组：高炎症（Hyperinflammatory, HI）亚组、免疫抑制（Immunosuppression, IS）亚组，以及合并免疫抑制与高炎症的（HI+IS）亚组。采用急性生理学与慢性健康状况评分系统II（APACHE II）评估患者病情严重程度。通过Kaplan-Meier（KM）曲线与COX回归分析，评估免疫功能障碍与患者30天、180天死亡率的相关性。

结果 本研究通过梳理相关文献，提出了初步诊断标准。本次分析共纳入43965例患者，其中约77%符合CIID的诊断标准。研究发现，免疫功能障碍患者的APACHE II评分更高，且三个亚组的APACHE II峰值存在差异。在COX模型中对比患者30天死亡率时，校正所有混杂因素后可见，IS亚组患者的死亡风险最低，HI亚组患者死亡风险最高。与之相反，在对比长期死亡率时，IS亚组患者的死亡风险最高，HI亚组患者死亡风险最低。综上，本研究提出并验证了针对CIID的诊断标准，亚组分析亦显示三个亚组间存在差异。

结论 本研究通过MIMIC-IV数据库验证了该诊断标准，证明其具有科学有效性与可靠性。