Introduction
Methods
Patients and definitions
Samples and cytokine measurements
Statistical analysis
Results
Patients
Characteristics | All patients (N= 163) | Mild or moderately severe AP (n= 138) | P- valueb | Severe AP (n= 25) | |||
---|---|---|---|---|---|---|---|
All (N= 25) | MMS <2 (n= 14) | P- value | MMS ≥2 (n= 11) | ||||
Men | 120 (73.6) | 96 (69.6) | 0.006 | 24 (96.0) | 13 (92.9) | NS | 11 (100.0) |
Age, years | 48 (18 to 87) | 49 (18 to 87) | NS | 43 (29 to 81) | 41 (29 to 81) | NS | 51 (29 to 69) |
Etiology | |||||||
Alcohol | 113 (69.3) | 91 (65.9) | 0.028 | 22 (88.0) | 11 (78.6) | NS | 11 (100) |
Biliary | 35 (21.5) | 34 (24.6) | 0.021 | 1 (4.0) | 1 (7.1) | NS | 0 |
Other cause | 11 (6.7) | 9 (6.5) | NS | 2 (8.0) | 2 (14.3) | NS | 0 |
Idiopathic | 4 (2.5) | 4 (2.9) | NS | 0 | 0 | NS | 0 |
Onset of symptoms, hr | 24 (1 to 72) | 24 (1 to 72) | NS | 24 (3 to 72) | 18 (3 to 48) | <0.001 | 48 (24 to 72) |
C-reactive protein, mg/L | 19 (3 to 435) | 16 (3 to 426) | 0.002 | 94 (3 to 435) | 30 (3 to 229) | <0.001 | 294 (22 to 435) |
Creatinine, μmol/L | 64 (31 to 1086) | 62 (31 to 313) | <0.001 | 92 (47 to 1086) | 68 (47 to 147) | <0.001 | 248 (92 to 1086) |
Calcium, mmol/L | 2.2 (1.27 to 2.73) | 2.23 (1.27 to 2.73) | <0.001 | 1.86 (1.39 to 2.30) | 2.04 (1.49 to 2.30) | 0.013 | 1.67 (1.39 to 2.17) |
Length of hospital stay, days | 6 (1 to 93) | 5 (1 to 41) | <0.001 | 26 (1 to 93) | 28 (1 to 93) | NS | 17 (1 to 49) |
Mechanical ventilation | 25 (15.3) | 2 (1.4) | <0.001 | 23 (92.0) | 13 (92.9) | NS | 10 (90.9) |
Renal replacement therapy | 16 (9.8) | 0 | <0.001 | 16 (64.0) | 7 (50.0) | NS | 9 (81.8) |
OD within 24 hours | 30 (18.4) | 10 (7.2) | <0.001 | 20 (80.0) | 9 (64.3) | NS | 11 (100) |
OD on days 1 to 7 | 5 (3.1) | 0 | <0.001 | 5 (20.0) | 5 (37.5) | NS | 0 (0) |
Mortality | 8 (4.9) | 1 (0.7) | 0.014 | 7 (28.0) | 2 (14.3) | NS | 5 (45.5) |
Cytokine profiles of patients with severe acute pancreatitis
All patients (N= 163) | Admission MMS <2 (n= 142) | |||||
---|---|---|---|---|---|---|
Cytokines | Mild or moderately severe AP (n= 138) | P- valueb | Severe (n= 25) | Mild or moderately severe AP (n= 128) | P- valueb | Severe AP (n= 14) |
G-CSF | 119.7 (66.6-198.2) | <0.001 | 260.2 (132.5 to 1011.8) | 118.41 (66.6 to 174.3) | 0.0007 | 234.0 (151.2 to 531.1) |
GRO-α | 58.8 (35.7-92.3) | <0.001 | 128.2 (98.4 to 169.1) | 54.5 (33.2 to 82.5) | 0.002 (NS) | 118.5 (62.4 to 158.4) |
HGF | 1055.5 (764.7-1730.6) | <0.001 | 3613.0 (2055.3 to 6348.8) | 989.6 (753.6 to 1501.6) | <0.001 | 2202.6 (1554.3 to 3305.5) |
IL-2Rα | 214.2 (150.6-316.7) | <0.001 | 483.3 (385.6 to 673.3) | 209.5 (145.5 to 290.4) | 0.0015 (NS) | 449.7 (228.1 to 504.3) |
IL-6 | 59.7 (15.3-202.1) | <0.001 | 428.9 (138.5 to 1796.3) | 49.9 (14.7 to 185.6) | 0.0013 (NS) | 234.5 (66.2 to 1931.3) |
IL-8 | 26.6 (19.3-41.9) | <0.001 | 82.4 (46.4 to 115.6) | 25.41 (18.0 to 37.6) | <0.001 | 59.7 (32.0 to 102.8) |
IL-18 | 139.6 (91.6-187.1) | <0.001 | 202.8 (151.8 to 305.4) | 131.5 (90.7 to 181.5) | 0.062 (NS) | 162.4 (135.3 to 201.6) |
LIFc | 0 (0) | <0.001 | 1 (0 to 1) | 0 (0) | 0.002 (NS) | 1 (0 to 1) |
M-CSF | 14.5 (8.1-28.1) | <0.001 | 40.2 (18.6 to 68.6) | 12.4 (5.5 to 21.5) | 0.007 (NS) | 28.7 (12.2 to 52.0) |
MCP-1 | 49.0 (21.0-111.2) | <0.001 | 125.0 (64.6 to 199.6) | 47.6 (30.0 to 100.6) | 0.032 (NS) | 92.1 (36.3 to 185.2) |
MCP-3 | 17.4 (0.57-53.6) | <0.001 | 54.58 (24.3 to 98.7) | 16.3 (0.2 to 47.9) | 0.006 (NS) | 52.0 (16.5 to 102.1) |
β-NGF | 5.79 (3.65-9.1) | <0.001 | 11.3 (7.4 to 15.9) | 5.5 (3.4 to 8.5) | 0.007 (NS) | 10.4 (4.5 to 15.5) |
SCF | 114.1 (85.2-147.0) | 0.0008 | 155.8 (109.2 to 256.0) | 111.6 (82.0 to 143.3) | 0.012 (NS) | 148.5 (107.3 to 218.9) |
SDF-1α | 87.6 (53.5-151.5) | <0.001 | 163.6 (104.4 to 226.3) | 86.8 (52.8 to 148.5) | 0.010 (NS) | 171.3 (85.1 to 234.8) |
Cytokines | Mild or moderately severe AP (n= 138) | P- valueb | Severe AP (n= 25) |
---|---|---|---|
CTACK | 993.1 (746.4 to 1,556.1) | 0.033 (NS) | 693.3 (652.5 to 1,150.6) |
Eotaxinc | 1 (0 to 1) | 0.133 (NS) | 1 (0 to 1) |
FGF | 25.9 (8.6 to 44.6) | 0.123 (NS) | 19.4 (0.4 to 35.2) |
GM-CSFc | 0 (0) | 0.663 (NS) | 0 (0 to 1) |
IFN-γ | 99.5 (50.7 to 151.0) | 0.772 (NS) | 82.4 (50.9 to 149.5) |
IP-10 | 379.3 (244.5 to 594.0) | 0.475 (NS) | 446.2 (222.6 to 825.3) |
IL-1αc | 0 (0 to 1) | 0.473 (NS) | 1 (0 to 1) |
IL-1β | 1.9 (0.8 to 3.0) | 0.961 (NS) | 1.9 (0.5 to 3.4) |
IL-1Ra | 121.1 (64.8 to 260.0) | 0.131 (NS) | 202.6 (70.9 to 669.8) |
IL-2 | 7.6 (2.2 to 13.4) | 0.796 (NS) | 6 to 7 (1.7 to 12.9) |
IL-3c | 0 (0) | 0.008 (NS) | 0 (0 to 1) |
IL-4 | 5.1 (2.6 to 7.5) | 0.261 (NS) | 3.8 (2.3 to 6.4) |
IL-5 | 2.7 (1.6 to 4.1) | 0.091 (NS) | 1.8 (1.0 to 3.4) |
IL-7 | 5.9 (3.9 to 10.5) | 0.482 (NS) | 5.2 (3.9 to 9.4) |
IL-9 | 19.5 (7.3 to 37.8) | 0.410 (NS) | 16.1 (1.7 to 38.7) |
IL-10 | 8.2 (3.9 to 17.7) | 0.012 (NS) | 15.8 (6.2 to 42.3) |
IL-12p70 | 18.7 (11.2 to 40.4) | 0.442 (NS) | 15.5 (9.0 to 36.5) |
IL-12p40c | 0 (0) | 0.691 (NS) | 0 (0) |
IL-13 | 7.2 (3.9 to 13.5) | 0.249 (NS) | 6.5 (2.6 to 12.1) |
IL-15c | 0 (0) | 0.018 (NS) | 0 (0 to 1) |
IL-16 | 220.2 (99.9 to 786.8) | 0.120 (NS) | 341.3 (157.2 to 980.1) |
IL-17A | 79.8 (33.2 to 155.9) | 0.084 (NS) | 45.8 (9.2 to 98.4) |
MIP-1α | 6.2 (3.7 to 8.0) | 0.215 (NS) | 4.6 (2.4 to 7.1) |
MIP-1β | 67.1 (42.6 to 90.2) | 0.830 (NS) | 63.6 (40.1 to 95.8) |
MIF | 695.8 (348.5 to 1,553.9) | 0.004 (NS) | 1461.2 (713.4 to 4,529.4) |
MIG | 1,415.5 (821.0 to 2,348.2) | 0.021 (NS) | 2,147.5 (1,257.4 to 4,268.7) |
PDGF-BB | 1,183.6 (360.4 to 2,475.2) | 0.063 (NS) | 583.3 (207.8 to 1,427.3) |
RANTES | 2,905.6 (1,110.3 to 4,511.1) | 0.093 (NS) | 1,877.2 (787.5 to 3,090.9) |
SCGF-β | 31452.4 (21610.3 to 46978.0) | 0.004 (NS) | 47129.9 (30743.1 to 56343.2) |
TRAIL | 57.4 (33.3 to 92.0) | 0.042 (NS) | 84.8 (51.8 to 122.7) |
TNF-α | 20.8 (10.3 to 31.9) | 0.730 (NS) | 18.2 (9.7 to 31.5) |
TNF-βc | 0 (0 to 1) | 0.187 (NS) | 0 (0) |
VEGF | 29.9 (17.7 to 71.1) | 0.436 (NS) | 23.6 (17.4 to 64.2) |
Cytokines | Spearman’s r | P- value |
---|---|---|
M-CSF | 0.62 | <0.001 |
HGF | 0.67 | <0.001 |
IL-8 | 0.67 | <0.001 |
MCP-1 | 0.71 | <0.001 |
G-CSF | 0.72 | <0.001 |
Predictive marker with optimal cutoff point | AUC | Sensitivity (%) | Specificity (%) | LR+ | LR- | DOR |
---|---|---|---|---|---|---|
IL-6 (>501.6 pg/ml) | 0.81 (0.72 to 0.90) | 48.0 (30.0 to 66.5) | 93.5 (88.1 to 96.5) | 7.4 (3.5 to 15.6) | 0.56 (0.38 to 0.81) | 13.2 (4.7 to 37.3) |
HGF (>3,020.1 pg/ml) | 0.87 (0.81 to 0.94) | 60.0 (40.7 to 0.77) | 92.8 (87.1 to 96.0) | 8.3 (4.2 to 16.3) | 0.43 (0.27 to 0.70) | 19.2 (6.9 to 53.6) |
IL-6 + HGF | 0.89 (0.82 to 0.96) | 72.0 (52.4 to 85.7) | 89.9 (83.7 to 93.9) | 7.1 (4.1 to 12.3) | 0.31 (0.17 to 0.59) | 22.8 (8.1 to 64.0) |
CRP (>227 mg/L) | 0.692 (0.57 to 0.82) | 40.0 (23.4 to 59.3) | 93.5 (88.0 to 96.5) | 6.1 (2.8 to 13.6) | 0.64 (0.47 to 0.89) | 9.6 (3.4 to 27.2) |
Creatinine (>141 μmol/L) | 0.76 (0.65 to 0.88) | 40.0 (23.4 to 59.3) | 96.3 (91.7 to 98.4) | 10.9 (4.1 to 29.1) | 0.62 (0.45 to 0.86) | 17.5 (5.3 to 57.9) |
Calcium (<1.91 mmol/L) | 0.81 (0.70 to 0.91) | 57.9 (36.3 to 76.9) | 93.2 (87.6 to 96.4) | 8.5 (4.1 to 17.8) | 0.45 (0.27 to 0.77) | 18.8 (6.0 to 58.4) |
Predicting severe acute pancreatitis in patients with modified Marshall score <2 upon admission
Severe AP patients | IL-8 >88.1 pg/ml | HGF >3,020.1 pg/ml | G-CSF >477.7 pg/ml | CRP >227 mg/L | Creatinine >141 μmol/L | Calcium <1.91 mmol/L |
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1 | - | - | - | - | - | - |
2 | - |
+
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+
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3 | - | - | - | - | - | - |
4 |
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| - | - | - | - |
b
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5 | - |
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+
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b
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6 | - |
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b
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7 | - | - | - | - |
+
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b
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8 | - | - | - | - | - |
+
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9 | - | - | - | - | - | - |
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+
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11 | - | - | - | - | - | - |
12 |
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13 | - |
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14 |
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Predictive marker and optimal cutoff point | AUC | Sensitivity (%) | Specificity (%) | LR+ | LR- | DOR |
---|---|---|---|---|---|---|
IL-8 (>88.1 pg/ml) | 0.79 (0.68 to 0.90) | 25.6 (11.7 to 54.7) | 95.3 (90.2 to 97.8) | 6.1 (2.0 to 19.0) | 0.75 (0.54 to 1.05) | 8.1 (2.0 to 33.6) |
HGF (>3,020.1 pg/ml) | 0.83 (0.73 to 0.92) | 28.6 (11.7 to 54.7) | 95.3 (0.90 to 97.8) | 6.1 (2.0 to 19.0) | 0.75 (0.54 to 1.05) | 8.1 (2.0 to 33.6) |
G-CSF (>477.7 pg/ml) | 0.78 (0.65 to 0.90) | 35.6 (16.3 to 61.2) | 96.1 (91.2 to 98.3) | 9.1 (3.0 to 27.7) | 0.67 (0.45 to 0.99) | 13.7 (3.3 to 56.1) |
CRP (>227 mg/L) | 0.54 (0.37 to 0.70) | 7.1 (1.3 to 31.5) | 95.3 (90.2 to 97.8) | 1.5 (0.2 to 11.8) | 0.97 (0.2 to 11.8) | 1.6 (0.2 to 14.0) |
Creatinine (>141 μmol/L) | 0.62 (0.45 to 0.79) | 7.1 (1.3 to 31.5) | 99.2 (95.7 to 99.9) | 9.1 (0.6 to 37.2) | 0.94 (0.91 to 1.08) | 9.7 (0.57 to 164.2) |
Calcium (<1.91 mmol/L) | 0.74 (0.60 to 0.88) | 36.4 (15.2 to 64.6) | 94.3 (88.7 to 97.2) | 6.4 (2.2 to 18.5) | 0.68 (0.43 to 1.06) | 9.5 (2.2 to 40.2) |
G-CSF + IL-8 + HGF | 57.1 (32.6 to 78.6) | 90.6 (84.3 to 94.6) | 6.1 (3.0 to 12.3) | 0.47 (0.26 to 0.87) | 12.9 (3.8 to 43.4) |
Predicting severe acute pancreatitis in patients with admission modified Marshall scores ≥2
Discussion
Conclusions
Key messages
-
The levels of 14/47 cytokines upon admission to the hospital were higher in patients with severe AP than in those with mild or moderately severe AP.
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IL-6 and HGF were independent predictors of severe AP.
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The predictive value of IL-6 and HGF was comparable to that of CRP, creatinine and calcium.
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Many patients who will develop severe AP, did not have signs of OD upon admission to hospital.
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IL-8, HGF and G-CSF is able to predict severe AP in patients without clinical signs of OD at the time of hospital admission.