A total of 119 patients (62 men and 57 women) were included in this study, and 88 (73.9%) of these patients were still in the ICU on day 3. Of the included patients, 58 (48.7%) were immunocompromised. Baseline characteristics of the patients are shown in Table 1. The median age of the patients was 70.0 years (IQR 58.0–79.5), and immunocompromised patients was significantly younger than immunocompetent patients (P < 0.001). Sepsis was diagnosed in 40 patients (33.6%), and septic shock was diagnosed in 60 (50.4%) patients. The median initial SOFA score and mean SAPS 3 on day 1 were 9.0 (6.5–11.5) and 75.5 ± 14.9, respectively, and both scores were significantly higher in immunocompromised patients (P = 0.019 for SOFA; P = 0.004 for SAPS 3). The median presepsin level at day 1 was 1254.0 pg/mL (730.5–2569.5) and was significantly higher in immunocompromised patients (P = 0.024). Among the cases, 53 (44.5%) had hypoxemia requiring invasive ventilation and 77 (64.7%) needed vasopressor support.
As shown in Fig. 1, we compared presepsin and procalcitonin levels according to the presence of sepsis and immune status. Amongst all patients, the median presepsin level was the highest in patients with septic shock (1766.5 [771.0–2809.5]) and the lowest in patients without septic shock (753.0 [603.5–1092.0]); this difference between patients with and without septic shock was significant (P < 0.001). The median presepsin level in patients with sepsis was also significantly higher than that of patients without sepsis (1203.0 [773.0–2484.0] vs. 753.0 [603.5–1092.0]; P = 0.009). In immunocompromised patients with sepsis or septic shock, the median presepsin levels were significantly higher than those of patients without sepsis or septic shock (1708.0 [851.5–3017.0] vs. 689.0 [510.0–862.5]; P = 0.004]; 1946.0 [1125.5–3376.5] vs. 689.0 [510.0–862.5]; P < 0.001]). Similarly, additional results showed a significant difference in median procalcitonin values among patients in the no sepsis, sepsis, and septic shock groups (no sepsis, 0.1 [0.1–0.4]; sepsis, 5.7 [0.5–14.7]; septic shock, 20.1 [5.9–59.0]; P < 0.001), and among patients in the immunocompromised subgroup (no sepsis, 0.3 [0.1–0.5]; sepsis, 3.6 [0.6–31.7]; septic shock, 31.7 [5.7–59.0]; P < 0.001).
ROC curves were generated to compare the presepsin and procalcitonin levels for diagnosing sepsis or septic shock (Fig. 2 and Table 2). In all patients, presepsin showed an area under the curve (AUC) of 0.736 (95% CI, 0.637–0.834), with 50% sensitivity and 94.7% specificity, at cutoff point ≥ 1632; however, procalcitonin showed an AUC of 0.898 (95% CI, 0.819–0.976), with 87% sensitivity and 89.5% specificity, at cutoff point ≥ 0.64. According to this comparison, the AUC of procalcitonin was higher than that of presepsin (AUC 0.898 vs. 0.736, P = 0.007) (Fig. 2A). In the immunocompromised subgroup, presepsin showed an AUC of 0.87 (95% CI, 0.765–0.975), with 66% sensitivity and 100% specificity, at cutoff point ≥ 1248. While procalcitonin showed an AUC of 0.892 (95% CI, 0.764–1), with 90% sensitivity and 87.5% specificity, in immunocompromised patients. The AUC between the two biomarkers was not significantly different (AUC 0.870 vs. 0.892, P = 0.766).
Table 2
Validity of presepsin and procalcitonin in diagnosis of sepsis or septic shock
Variable
|
Cutoff
|
AUC
|
Sensitivity
|
Specificity
|
+ PV
|
- PV
|
P value
|
In all patients
|
|
|
|
|
|
|
|
Presepsin
|
1632
|
0.736
|
50.0
|
94.7
|
96.2
|
25.4
|
< 0.001
|
Procalcitonin
|
0.64
|
0.898
|
87.0
|
89.5
|
96.7
|
55.2
|
< 0.001
|
In immunocompromised patients
|
|
|
|
|
|
|
Presepsin
|
1248
|
0.870
|
66.0
|
100
|
100
|
32.0
|
< 0.001
|
Procalcitonin
|
0.5
|
0.892
|
90.0
|
87.5
|
97.8
|
58.3
|
< 0.001
|
+PV, positive predictive value; -PV, negative predictive value |
Table 3 lists the demographic differences between survivors and non-survivors among 88 patients with sepsis. Twelve patients who died before 3 days after ICU admission were excluded from this analysis. A significantly larger proportion of immunocompromised patients was observed among non-survivors than among survivors. Unsurprisingly, non-survivors had significantly higher SAPS 3 and SOFA score at ICU admission. Notably, presepsin levels on day 3, but not on day 1, were significantly higher in patients who died. Furthermore, the proportion of patients with ΔPresepsin + was significantly higher among non-survivors than among survivors; a similar result was observed in the subgroup of immunocompromised patients with sepsis (Supplementary Table 1). After adjusting for potential confounding factors, ΔPresepsin + remained significantly associated with in-hospital mortality of immunocompromised patients with sepsis (adjusted OR, 6.22; 95% CI, 1.33–29.06; P = 0.02) (Table 3).
Table 3
Clinical and laboratory characteristics of survived and died patients with sepsis (N = 88)
|
Survived patient
(n = 50)
|
Died patient
(n = 38)
|
P value
|
Sex, male
|
29 (58.0)
|
18 (47.4)
|
0.439
|
Age, yrs
|
71.0 (61.0–79.0)
|
69.5 (54.0–83.0)
|
0.879
|
Immunocompromised patients
|
18 (36.0)
|
23 (60.5)
|
0.039
|
Charlson comorbidity index
|
6.0 (4.0–8.0)
|
5.0 (4.0–7.0)
|
0.589
|
SAPS3 score
|
72.2 ± 11.6
|
83.6 ± 12.9
|
< 0.001
|
SOFA score
|
8.0 (7.0–11.0)
|
11.0 (8.0–13.0)
|
0.002
|
Use of vasopressor on Day 1
|
35 (70.0)
|
29 (76.3)
|
0.676
|
Use of invasive ventilation on Day 1
|
15 (30.0)
|
21 (55.3)
|
0.030
|
Systolic BP at ICU admission
|
79.0 (70.0–89.0)
|
82.0 (71.0–90.0)
|
0.787
|
Diastolic BP at ICU admission
|
47.5 (41.0–55.0)
|
50.0 (41.0–56.0)
|
0.385
|
Heart rate at ICU admission
|
124.2 ± 25.8
|
138.6 ± 28.2
|
0.014
|
Respiratory rate at ICU admission
|
28.0 (23.0–34.0)
|
31.5 (26.0–38.0)
|
0.076
|
Leukocyte count, Day 1
|
8.9 (4.3–17.3)
|
10.0 (3.0–16.5)
|
0.768
|
Neutrophil count, Day 1
|
7.1 (3.3–15.2)
|
8.6 (2.8–14.1)
|
0.714
|
Platelet count, Day 1
|
156.5 (52.0–235.0)
|
64.0 (34.0–143.0)
|
0.006
|
Lactate, Day 1
|
2.4 (1.3–3.9)
|
3.4 (1.9–7.1)
|
0.078
|
Lactate, Day 3
|
1.4 (1.0–2.2)
|
2.6 (1.6–5.8)
|
< 0.001
|
Procalcitonin, Day 1
|
10.6 (1.5–49.6)
|
7.2 (2.3–27.6)
|
0.383
|
Procalcitonin, Day 3
|
3.5 (0.7–13.8)
|
7.8 (2.5–40.6)
|
0.022
|
ΔProcalcitonin+
|
4 (8.0)
|
14 (36.8)
|
0.002
|
Presepsin, Day 1
|
1209.0 (623.0–2559.0)
|
1643.0 (777.0–3310.0)
|
0.135
|
Presepsin, Day 3
|
933.0 (638.0–1571.0)
|
1965.0 (1149.0–3423.0)
|
0.001
|
ΔPresepsin+
|
16 (32.0)
|
28 (73.7)
|
< 0.001
|
SAPS3, Simplified Acute Physiology Score 3; SOFA. Sequential Organ Failure Assessment; ΔProcalcitonin+, serum procalcitonin level on day 3 minus day 1 > 0; ΔPresepsin+, plasma presepsin level on day 3 minus day 1 > 0. |
Table 4
Logistic regression analysis for the in-hospital mortality in immunocompromised patients.
|
Univariate analysis
|
Multivariate analysis
|
OR (95% CI)
|
P value
|
OR (95% CI)
|
P value
|
SAPS3 score
|
1.04 (0.98–1.09)
|
0.212
|
|
|
SOFA score
|
1.08 (0.87–1.34)
|
0.480
|
|
|
Systolic BP at ICU admission
|
1.04 (0.99–1.10)
|
0.092
|
|
|
Diastolic BP at ICU admission
|
1.05 (0.99–1.12)
|
0.076
|
|
|
Heart rate at ICU admission
|
1.01 (0.98–1.03)
|
0.510
|
|
|
Respiratory rate at ICU admission
|
1.01 (0.92–1.11)
|
0.800
|
|
|
Procalcitonin, Day 1
|
0.98 (0.96–1.01)
|
0.140
|
|
|
Procalcitonin, Day 3
|
1.02 (0.98–1.05)
|
0.331
|
|
|
ΔProcalcitonin+
|
6.15 (1.14–33.20)
|
0.035
|
5.45 (0.72–41.17)
|
0.100
|
Presepsin, Day 1
|
1.00 (1.00–1.00)
|
0.661
|
|
|
Presepsin, Day 3
|
1.00 (1.00–1.00)
|
0.313
|
|
|
ΔPresepsin+
|
7.20 (1.79–29.01)
|
0.006
|
6.22 (1.33–29.06)
|
0.020
|
SAPS3, Simplified Acute Physiology Score 3; SOFA. Sequential Organ Failure Assessment; ICU, intensive care unit; ΔProcalcitonin+, serum procalcitonin level on day 3 minus day 1 > 0; ΔPresepsin+, plasma presepsin level on day 3 minus day 1 > 0. |
Figure 3 depicts the changes in presepsin and procalcitonin levels in non-survivors. The median presepsin levels on day 3 were significantly higher than those on day 1 in all patients who died in the hospital (1965.0 [1149.0–3423.0] vs. 1643.0 [777.0–3310.0]; P = 0.046). In addition, in a subgroup of immunocompromised patients, the median presepsin levels on day 3 were significantly higher than those on day 1 (1449.0 [987.5–3594.0] vs. 1116.0 [773.0–3141.5]; P = 0.018). There was no significant difference observed in procalcitonin levels between day 1 and day 3 in all patients or in the immunocompromised subgroup.