Patient characteristics
Baseline characteristics of 49 SS, 19 SWS and 6 age- and sex-matched healthy controls are shown in Table 1. The levels of sCD40L in healthy controls were 469.50 (406.83-547.36) pg/mL, and the sCD40L levels in SWS and SS were significantly increased. The difference between the two groups was statistically significant (Table 1, P=0.000 vs healthy controls). Compared with SWS, SS also exhibited increased APACHE-II (P=0.001), SOFA (P<0.001), ISTH (P<0.001), and JAAM (P<0.001) scores; AKI (P=0.000), ARDS (P=0.000), PT-INR (P=0.001), fibrinogen (P=0.022), FDP (P<0.001), D-dimer (P<0.001), and lactate (P=0.006) levels; 28-day mortality (P=0.001), longer length of stay in the ICU, and lower PaO2/FiO2 ratio (Table 1). However, type of surgery did not differ between the SS and SWS groups.
Table 1, Baseline demographic and clinical characteristics of the studied population group
|
Healty control
n=6
|
SS
n=19
|
SWS
n=49
|
P
|
Sex(male/female)
|
3/3
|
12/7
|
34/15
|
0.586
|
Age(years)-median(p25-p75)
|
53.00(42.25-62.00)
|
76.00(71.00-81.00)
|
61.00(45.00-73.00)
|
0.005
|
sCD40L(pg/ml)-median(p25-p75)
|
469.50(406.83-547.36)
|
831.36(526.58-981.72)
|
1022.68(554.85-2215.13)
|
0.000
|
APACHE Ⅱ score-median(p25-p75)
|
|
9.00(7.00-11.00)
|
14.00(11.00-16.00)
|
0.001
|
SOFA score-median(p25-p75)
|
|
1.00(0.00-2.00)
|
8.00(6.00-10.00)
|
0.000
|
ISTH score-median(p25-p75)
|
|
0.00(0.00-2.00)
|
3.00(2.50-4.50)
|
0.000
|
JAAM score-median(p25-p75)
|
|
1.00(0.00-2.00)
|
4.00(3.00-5.00)
|
0.000
|
PT-INR-median(p25-p75)
|
|
1.16(1.12-1.34)
|
1.41(1.21-1.66)
|
0.001
|
aPTT(seconds)-median(p25-p75)
|
|
41.10(36.10-81.40)
|
49.40(41.55-60.85)
|
0.080
|
fibrinogen(g/L)-median(p25-p75)
|
|
3.10(1.96-3.60)
|
3.94(2.50-5.88)
|
0.022
|
FDP(ug/dl)-median(p25-p75)
|
|
5.46(3.60-13.42)
|
21.81(12.24-48.66)
|
0.000
|
D-Dimer(ug/ml)-median(p25-p75)
|
|
1.71(0.80-3.58)
|
4.81(3.24-10.11)
|
0.000
|
platelet-median*103/mm3 (p25-p75)
|
|
157.00(136.00-191.00)
|
136.00(77.00-214.50)
|
0.305
|
leukocytes-median*103/mm3(p25-p75)
|
|
7.87(5.28-11.90)
|
10.62(7.50-15.44)
|
0.030
|
Lactate(mmol/L)-median(p25-p75)
|
|
1.50(0.90-1.80)
|
2.00(1.30-3.90)
|
0.006
|
28 days mortality (%)
|
|
0/19(0)
|
20/49(40.82)
|
0.000
|
length of stay in the ICU(days)-median(p25-p75)
|
|
3.74(3-5)
|
21.57(13-28)
|
0.000
|
AKI-n (%)
|
|
0/19(0)
|
16/49(32.65)
|
0.000
|
sepsis-induced liver injury-n (%)
|
|
0/19(0)
|
3/49(6.12)
|
0.277
|
ARDS-n (%)
|
|
0/19(0)
|
21/49(42.86)
|
0.000
|
PaO2/FiO2 ratio
|
|
318.9(300-330)
|
234.1(170-300)
|
0.000
|
Subtotal gastrectomy
|
|
3/19(15.79)
|
10/49(20.41)
|
0.549
|
enteroanastomosis
|
|
8/19(42.11)
|
19/49(38.77)
|
0.805
|
Cholecystectomy
|
|
3/19(15.79)
|
8/49(16.33)
|
0.958
|
Choledocholithotomy
|
|
5/19(26.31)
|
12/49(24.49)
|
0.878
|
SWS=surgical patients without sepsis; SS=surgical sepsis patients; p 25-75 = percentile 25th-75th; APACHE II = Acute Physiology and Chronic Health Evaluation II; SOFA =Sepsis-related Organ Failure Assessment; ISTH =International Society on
Thrombosis and Haemostasis , JAAM =Japanese Association for Acute Medicine; PT-INR =prothrombin time international normalized ratio; aPTT=activated partial thromboplastin time; FDP=Fibrinogen degradation product; AKI=acute kidney injury; ARDS=acute respiratory distress syndrome; PaO2/FiO2 =pressure of arterial oxygen/fraction inspired oxygen
A total of 27 strains were isolated from the blood samples of 20 patients in the SS group, including seven strains with methicillin-resistant coagulase-negative Staphylococcus; five with Acinetobacter baumannii; five with non-Candida albicans; three with Enterococcus faecium, two each with methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae; and one with Escherichia coli. More than two strains were isolated from the blood samples of 8 patients.
Demographic and clinical characteristics of nonsurvivors and survivors in surgical sepsis patients
In total, 20 SS patients died, and 29 patients survived. The demographic and clinical features of these patients are shown in Table 2 and Supplemental Table 1. Nonsurviving patients had higher serum sCD40L (P=0.009) and aPTT than surviving patients at day 2 (P=0.020) and higher lactate at day 3 (P=0.001). In addition, older age (P=0.023) was observed in the group of nonsurviving patients compared with the group of surviving SS patients. No significant differences in sex, presence of septic shock, site of infection, length of stay in the ICU, PaO2/FiO2 ratio, incidence of AKI, ARDS, or type of surgery were noted between nonsurvivors and survivors. In addition, on days 1, 2, and 3 after ICU admission, no statistically significant differences in APACHE II score, SOFA score, ISTH score, JAAM score, PT-INR, fibrinogen, FDP, D-dimer, platelet and leukocytes were noted between the nonsurviving and surviving groups of SS.
Table 2, Biochemical characteristics of survivor and nonsurvivor surgical sepsis patients on day 2 of ICU admission
|
Survivor(n=29)
|
Non-survivor(n=20)
|
P
|
Gender(male/female)
|
22/7
|
12/8
|
0.236
|
Age(years)-median(p25-p75)
|
56.00(31.50-64.00)
|
71.00(52.25-77.25)
|
0.023
|
Septic shock− n (%)
|
17(58.6)
|
10(50.0)
|
0.551
|
Site of infection
|
|
|
0.508
|
Respiratory − n (%)
|
5(17.2)
|
5(25.0)
|
|
Abdominal − n (%)
|
24(82.8)
|
15(75.0)
|
|
APACHE Ⅱ score-median(p25-p75)
|
12.00(8.00-16.50)
|
14.00(11.25-17.00)
|
0.156
|
SOFA score-median(p25-p75)
|
6.00(5.00-10.00)
|
8.50(6.00-10.00)
|
0.216
|
ISTH score-median(p25-p75)
|
4.00(2.00-5.00)
|
3.00(3.00-4.75)
|
0.901
|
JAAM score-median(p25-p75)
|
4.00(2.50-5.00)
|
4.00(2.50-4.75)
|
0.835
|
PT-INR-median(p25-p75)
|
1.36(1.25-1.72)
|
138.5(128.25-170.75)
|
0.760
|
aPTT(seconds)-median(p25-p75)
|
51.00(43.60-66.95)
|
68.65(53.20-113.95)
|
0.020
|
fibrinogen(g/L)-median(p25-p75)
|
3.74(2.55-6.70)
|
2.83(1.70-4.78)
|
0.106
|
FDP(ug/dl)-median(p25-p75)
|
16.96(10.43-33.01)
|
20.40(7.37-32.33)
|
0.823
|
D-Dimer(ug/ml)-median(p25-p75)
|
3.96(2.95-7.61)
|
3.86(2.19-7.86)
|
0.502
|
platelet- median*103/mm3 (p25-p75)
|
109.00(47.00-191.00)
|
124.50(65.25-174.25)
|
0.903
|
leukocytes-median*103/mm3(p25-p75)
|
13.71(6.83-17.93)
|
13.91(9.06-19.22)
|
0.376
|
Lactate(mmol/L)-median(p25-p75)
|
2.10(1.30-3.15)
|
2.75(1.65-5.60)
|
0.203
|
sCD40L(pg/ml)-median(p25-p75)
|
747.21(422.46-981.47)
|
1214.72(696.28-2089.57)
|
0.009
|
length of stay in the ICU(days)-
median(p25-p75)
|
17.62(5-20)
|
12.55(7-19)
|
0.341
|
AKI –n (%)
|
10/29(34.48)
|
6/20(30.00)
|
0.749
|
ARDS-n (%)
|
12/29(41.38)
|
9/20(45.00)
|
0.806
|
PaO2/FiO2 ratio
|
232.9(170-300)
|
236.0(170-310)
|
0.900
|
Subtotal gastrectomy
|
5/29(17.24)
|
5/20(25.00)
|
0.518
|
enteroanastomosis
|
11/29(37.93)
|
8/20(40.00)
|
0.889
|
Cholecystectomy
|
5/29(17.24)
|
3/20(15.00)
|
0.839
|
Choledocholithotomy
|
8/29(27.59)
|
4/20(20.00)
|
0.554
|
p25-75 = percentile 25th-75th; APACHE II = Acute Physiology and Chronic Health Evaluation II; SOFA =Sepsis-related Organ Failure Assessment; ISTH =Thrombosis and Haemostasis , JAAM =Japanese Association for Acute Medicine; PT-INR =prothrombin time international normalized ratio; aPTT=activated partial thromboplastin time; FDP=Fibrinogen degradation product; AKI=acute kidney injury; ARDS=acute respiratory distress syndrome; PaO2/FiO2 =pressure of arterial oxygen/fraction inspired oxygen
Predictive factors for 28-day mortality
The area under the curve (AUC) for serum sCD40L levels at day 2 (95% confidence interval (CI)=0.570-0.871, P=0.009) could predict mortality at 28 days, and the sensitivity and specificity approached 60.0% and 79.3%, respectively (Figure 1). Kaplan-Meier survival analysis showed that patients with higher serum sCD40L levels at day 1 (P=0.035), day 2 (P=0.005), and day 3 (P=0.003) had a higher risk of death at 28 days than patients with lower levels (Figure 2). In addition, patient age ≥65 years (odds ratio=7.929; 95% CI=1.809 to 34.750; P=0.006) and serum sCD40L levels at day 2 ≥1028.75 pg/mL (odds ratio=7.888; 95% CI= 1.758 to 35.395; P=0.007) were significant predictive factors for 28-day mortality in multiple logistic regression analysis.
Association between sCD40L levels and other clinical parameters in patients with surgical sepsis
In addition, no relationship was observed between serum sCD40L levels and APACHE II, SOFA, ISTH, and JAAM score as well as PT-INR, fibrinogen, FDP, D-dimer, leukocyte, platelets and lactate levels in the SS group on days 1, 2, and 3 after ICU admission (Table 3).
Table 3, Association between sCD40L levels and other clinical parameters in patients with surgical sepsis
|
sCD40L day1
|
|
|
sCD40L day2
|
|
sCD40L day3
|
Rho
|
P
|
|
Rho
|
P
|
Rho
|
P
|
APACHE Ⅱ score
|
-0.215
|
0.138
|
-0.045
|
0.761 -0.208
|
0.151
|
SOFA score
|
-0.158
|
0.279
|
-0.073
|
0.617 0.069
|
0.639
|
ISTH score
|
0.016
|
0.914
|
-0.051
|
0.726 0.098
|
0.501
|
JAAM score
|
-0.016
|
0.916
|
0.016
|
0.912 0.216
|
0.136
|
PT-INR
|
0.146
|
0.318
|
0.166
|
0.255 0.055
|
0.708
|
aPTT
|
0.132
|
0.367
|
-0.027
|
0.851 -0.043
|
0.769
|
fibrinogen
|
-0.092
|
0.529
|
-0.065
|
0.655 -0.202
|
0.163
|
FDP
|
0.131
|
0.370
|
0.137
|
0.347 0.085
|
0.562
|
D-Dimer
|
0.171
|
0.240
|
0.077
|
0.600 0.069
|
0.636
|
platelet
|
0.046
|
0.752
|
0.122
|
0.405 -0.003
|
0.983
|
leukocytes
|
0.223
|
0.124
|
0.158
|
0.277 0.061
|
0.679
|
lactate
|
-0.050
|
0.733
|
0.194
|
0.181 0.111
|
0.447
|
APACHE II = Acute Physiology and Chronic Health Evaluation II; SOFA =Sepsis-related Organ Failure Assessment; ISTH =Thrombosis and Haemostasis , JAAM =Japanese Association for Acute Medicine; PT-INR =prothrombin time international normalized ratio; aPTT=activated partial thromboplastin time; FDP=Fibrinogen degradation product