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Abstract：
BACKGROUND: The presence of nucleated red blood cells (NRBCs) in the peripheral blood of critically ill patients is associated with poor outcome. Evidence regarding the predictive value of NRBCs in patients with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) remains elusive. The aim of this study was to evaluate the predictive validity of NRBCs in these patients.
METHODS: Daily NRBC values of adult patients with SARS-CoV-2-induced ARDS were assessed and their predictive validity for mortality was statistically evaluated. A cut-off level based on the patient\'s maximum NRBC value during ICU stay was calculated and further specified according to Youden\'s method. Based on this cut-off value, further analyses such as logistic regression models and survival were performed.
RESULTS: 413 critically ill patients with SARS-CoV-2-induced ARDS were analyzed. Patients who did not survive had significantly higher NRBC values during their ICU stay compared to patients who survived (1090/µl [310; 3883] vs. 140/µl [20; 500]; p < 0.0001). Patients with severe ARDS (n = 374) had significantly higher NRBC values during ICU stay compared to patients with moderate ARDS (n = 38) (490/µl [120; 1890] vs. 30/µl [10; 476]; p < 0.0001). A cut-off level of NRBC ≥ 500/µl was found to best stratify risk and was associated with a longer duration of ICU stay (12 [8; 18] vs. 18 [13; 27] days; p < 0.0001) and longer duration of mechanical ventilation (10 [6; 16] vs. 17 [12; 26] days; p < 0.0001). Logistic regression analysis with multivariate adjustment showed NRBCs ≥ 500/µl to be an independent risk factor of mortality (odds ratio (OR) 4.72; 95% confidence interval (CI) 2.95-7.62, p < 0.0001). Patients with NRBC values below the threshold of 500/µl had a significant survival advantage over those above the threshold (median survival 32 [95% CI 8.7-43.3] vs. 21 days [95% CI 18.2-23.8], log-rank test, p < 0.05). Patients who once reached the NRBC threshold of ≥ 500/µl during their ICU stay had a significantly increased long-term mortality (median survival 489 days, log-rank test, p = 0.0029, hazard ratio (HR) 3.2, 95% CI 1.2-8.5).
CONCLUSIONS: NRBCs predict mortality in critically ill patients with SARS-CoV-2-induced ARDS with high prognostic power. Further studies are required to confirm the clinical impact of NRBCs to eventually enhance decision making.
METHODS: Daily NRBC values of adult patients with SARS-CoV-2-induced ARDS were assessed and their predictive validity for mortality was statistically evaluated. A cut-off level based on the patient\'s maximum NRBC value during ICU stay was calculated and further specified according to Youden\'s method. Based on this cut-off value, further analyses such as logistic regression models and survival were performed.
RESULTS: 413 critically ill patients with SARS-CoV-2-induced ARDS were analyzed. Patients who did not survive had significantly higher NRBC values during their ICU stay compared to patients who survived (1090/µl [310; 3883] vs. 140/µl [20; 500]; p < 0.0001). Patients with severe ARDS (n = 374) had significantly higher NRBC values during ICU stay compared to patients with moderate ARDS (n = 38) (490/µl [120; 1890] vs. 30/µl [10; 476]; p < 0.0001). A cut-off level of NRBC ≥ 500/µl was found to best stratify risk and was associated with a longer duration of ICU stay (12 [8; 18] vs. 18 [13; 27] days; p < 0.0001) and longer duration of mechanical ventilation (10 [6; 16] vs. 17 [12; 26] days; p < 0.0001). Logistic regression analysis with multivariate adjustment showed NRBCs ≥ 500/µl to be an independent risk factor of mortality (odds ratio (OR) 4.72; 95% confidence interval (CI) 2.95-7.62, p < 0.0001). Patients with NRBC values below the threshold of 500/µl had a significant survival advantage over those above the threshold (median survival 32 [95% CI 8.7-43.3] vs. 21 days [95% CI 18.2-23.8], log-rank test, p < 0.05). Patients who once reached the NRBC threshold of ≥ 500/µl during their ICU stay had a significantly increased long-term mortality (median survival 489 days, log-rank test, p = 0.0029, hazard ratio (HR) 3.2, 95% CI 1.2-8.5).
CONCLUSIONS: NRBCs predict mortality in critically ill patients with SARS-CoV-2-induced ARDS with high prognostic power. Further studies are required to confirm the clinical impact of NRBCs to eventually enhance decision making.
摘要：
背景：危重患者外周血中存在有核红细胞（NRBC）与不良预后相关。关于SARS-CoV-2诱发的急性呼吸窘迫综合征（ARDS）患者中NRBC的预测价值的证据仍然难以捉摸。这项研究的目的是评估NRBC在这些患者中的预测有效性。
方法：评估SARS-CoV-2诱导的ARDS成年患者的每日NRBC值，并对其死亡率的预测效度进行统计学评估。根据ICU住院期间患者的最大NRBC值计算并根据Youden的方法进一步指定截止水平。根据这个截止值,我们进行了进一步分析,如logistic回归模型和生存率.
结果：分析413例SARS-CoV-2致ARDS的危重患者。与存活的患者相比，未存活的患者在ICU住院期间的NRBC值明显更高（1090/μl[310;3883]vs.140/μl[20;500];p<0.0001)。重度ARDS患者（n=374）在ICU住院期间的NRBC值明显高于中度ARDS患者（n=38）（490/μl[120;1890]vs.30/μl[10;476];p<0.0001)。发现NRBC的截止水平≥500/μl可以最好地分层风险，并且与ICU住院时间更长有关（12[8;18]vs.18[13;27]天；p<0.0001）和更长的机械通气持续时间（10[6;16]vs.17[12；26]天；p<0.0001）。多变量校正的Logistic回归分析显示，NRBC≥500/µl是死亡率的独立危险因素（比值比（OR）4.72；95％置信区间（CI）2.95-7.62，p<0.0001）。NRBC值低于阈值500/μl的患者比高于阈值的患者具有显着的生存优势（中位生存32[95％CI8.7-43.3]与21天[95%CI18.2-23.8]，对数秩检验，p<0.05)。在ICU入住期间达到NRBC阈值≥500/μl的患者的长期死亡率显着增加（中位生存期489天，对数秩检验，p=0.0029，风险比（HR）3.2，95%CI1.2-8.5）。
结论：NRBCs预测SARS-CoV-2诱导的ARDS危重患者的死亡率，具有较高的预后能力。需要进一步的研究来确认NRBC的临床影响，以最终提高决策。
方法：评估SARS-CoV-2诱导的ARDS成年患者的每日NRBC值，并对其死亡率的预测效度进行统计学评估。根据ICU住院期间患者的最大NRBC值计算并根据Youden的方法进一步指定截止水平。根据这个截止值,我们进行了进一步分析,如logistic回归模型和生存率.
结果：分析413例SARS-CoV-2致ARDS的危重患者。与存活的患者相比，未存活的患者在ICU住院期间的NRBC值明显更高（1090/μl[310;3883]vs.140/μl[20;500];p<0.0001)。重度ARDS患者（n=374）在ICU住院期间的NRBC值明显高于中度ARDS患者（n=38）（490/μl[120;1890]vs.30/μl[10;476];p<0.0001)。发现NRBC的截止水平≥500/μl可以最好地分层风险，并且与ICU住院时间更长有关（12[8;18]vs.18[13;27]天；p<0.0001）和更长的机械通气持续时间（10[6;16]vs.17[12；26]天；p<0.0001）。多变量校正的Logistic回归分析显示，NRBC≥500/µl是死亡率的独立危险因素（比值比（OR）4.72；95％置信区间（CI）2.95-7.62，p<0.0001）。NRBC值低于阈值500/μl的患者比高于阈值的患者具有显着的生存优势（中位生存32[95％CI8.7-43.3]与21天[95%CI18.2-23.8]，对数秩检验，p<0.05)。在ICU入住期间达到NRBC阈值≥500/μl的患者的长期死亡率显着增加（中位生存期489天，对数秩检验，p=0.0029，风险比（HR）3.2，95%CI1.2-8.5）。
结论：NRBCs预测SARS-CoV-2诱导的ARDS危重患者的死亡率，具有较高的预后能力。需要进一步的研究来确认NRBC的临床影响，以最终提高决策。
