Patient demographic and clinical characteristics
| Characteristic . | Retrospective derivation cohort, n = 221 . | Prospective derivation cohort, n = 305 . | Prospective validation cohort, n = 687 . | ||||
|---|---|---|---|---|---|---|---|
| ELISA negative, n = 175 . | ELISA positive, n = 46 . | ||||||
| HIPA positive . | HIPA negative . | HIPA positive . | HIPA negative . | HIPA positive . | HIPA negative . | ||
| No. (%) of patients, | 175 (79) | 22 (10) | 24 (11) | 26 (8.5) | 279 (91.5) | 53 (7.7) | 634 (92.3) |
| Female sex, % (n/N) | 37.2 (65/175) | 40.9 (9/22) | 37.5 (9/24) | 23.1 (6/26) | 34.8 (97/279) | 50.9 (27/53) | 36.4 (231/634) |
| Age, y | |||||||
| Median | 70.2 | 68.8 | 65.3 | 68.8 | 70.9 | 72.6 | 70.0 |
| IQR | 61.2; 79.0 | 57.3; 77.3 | 60.9; 73.3 | 58.9; 77.0 | 61.3; 77.6 | 66.4; 80.4 | 59.3; 78.9 |
| Range (min./max.) | 23.0; 95.0 | 33.5; 89.0 | 41.6; 84.9 | 24.7; 84.9 | 16.0; 94.0 | 28.9; 96.6 | 3.6; 113.0 |
| Clinical setting, % (n) | |||||||
| Internal medicine | 12.6 (22) | 4.5 (1) | 0 | 7.7 (2) | 14 (39) | 18.9 (10) | 19.9 (126) |
| Cardiology | 0.6 (1) | 4.5 (1) | 0 | 0 | 1.4 (4) | 1.9 (1) | 2.4 (15) |
| ICU | 8.6 (15) | 23 (5) | 17 (4) | 7.7 (2) | 15.4 (43) | 13.2 (7) | 15.6 (99) |
| General surgery | 2.9 (5) | 14 (3) | 12.5 (3) | 11.5 (3) | 5 (14) | 3.8 (2) | 4.9 (31) |
| Cardiovascular surgery | 2.9 (5) | 4.5 (1) | 4.2 (1) | 7.7 (2) | 5 (14) | 13.2 (7) | 4.6 (29) |
| Orthopedic surgery | 0 | 0 | 0 | 7.7 (2) | 0.7 (2) | 0 (0) | 0.8 (5) |
| External institutions | 72.6 (127) | 50 (11) | 66.7 (16) | 57.7 (15) | 58.4 (163) | 49.1 (26) | 51.9 (329) |
| 4T score | |||||||
| Median | 4 | 5 | 4 | 5 | 4 | 5 | 4 |
| IQR | 4; 5 | 4; 6 | 4; 6 | 4; 6 | 3; 4 | 4; 6 | 3; 4 |
| Range (min./max.) | 3; 7 | 3; 7 | 3; 7 | 0; 7 | 0; 7 | 3; 8 | 0; 7 |
| ELISA, OD | |||||||
| Median | 0.04 | 1.98 | 0.63 | 1.50 | 0.06 | ||
| IQR | 0.02; 0.06 | 0.98; 2.49 | 0.41; 1.03 | 0.69; 2.39 | 0.04; 0.11 | NA | |
| Range (min./max.) | 0.00; 0.25 | 0.44; 3.00 | 0.32; 1.92 | 0.25; 3.00 | 0.01; 2.81 | ||
| CLIA, U/mL | |||||||
| Median | 11.53 | 0.08 | 4.56 | 0.03 | 11.8 | 0.02 | |
| IQR | NA | 1.63; 22.96 | 0.02; 0.13 | 1.34; 11.14 | 0.01; 0.05 | 3.60; 47.95 | 0.00; 0.07 |
| Range (min./max.) | 0.15; 52.49 | 0.01; 0.79 | 0.20; >128 | 0.00; 1.27 | 0.35; > 128 | 0.00; 12.11* | |
| PaGIA, titer | |||||||
| Median | 32 | 0 | 16 | 0 | 16 | 1† | |
| IQR | NA | 8; 32 | 0; 1 | 8; 32 | 0; 0 | 8; >16 | 0; 2 |
| Range (min./max.) | 4; 64 | 0; 8 | 2; 512 | 0; 8 | 2; >16 | 0; >16‡ | |
| Characteristic . | Retrospective derivation cohort, n = 221 . | Prospective derivation cohort, n = 305 . | Prospective validation cohort, n = 687 . | ||||
|---|---|---|---|---|---|---|---|
| ELISA negative, n = 175 . | ELISA positive, n = 46 . | ||||||
| HIPA positive . | HIPA negative . | HIPA positive . | HIPA negative . | HIPA positive . | HIPA negative . | ||
| No. (%) of patients, | 175 (79) | 22 (10) | 24 (11) | 26 (8.5) | 279 (91.5) | 53 (7.7) | 634 (92.3) |
| Female sex, % (n/N) | 37.2 (65/175) | 40.9 (9/22) | 37.5 (9/24) | 23.1 (6/26) | 34.8 (97/279) | 50.9 (27/53) | 36.4 (231/634) |
| Age, y | |||||||
| Median | 70.2 | 68.8 | 65.3 | 68.8 | 70.9 | 72.6 | 70.0 |
| IQR | 61.2; 79.0 | 57.3; 77.3 | 60.9; 73.3 | 58.9; 77.0 | 61.3; 77.6 | 66.4; 80.4 | 59.3; 78.9 |
| Range (min./max.) | 23.0; 95.0 | 33.5; 89.0 | 41.6; 84.9 | 24.7; 84.9 | 16.0; 94.0 | 28.9; 96.6 | 3.6; 113.0 |
| Clinical setting, % (n) | |||||||
| Internal medicine | 12.6 (22) | 4.5 (1) | 0 | 7.7 (2) | 14 (39) | 18.9 (10) | 19.9 (126) |
| Cardiology | 0.6 (1) | 4.5 (1) | 0 | 0 | 1.4 (4) | 1.9 (1) | 2.4 (15) |
| ICU | 8.6 (15) | 23 (5) | 17 (4) | 7.7 (2) | 15.4 (43) | 13.2 (7) | 15.6 (99) |
| General surgery | 2.9 (5) | 14 (3) | 12.5 (3) | 11.5 (3) | 5 (14) | 3.8 (2) | 4.9 (31) |
| Cardiovascular surgery | 2.9 (5) | 4.5 (1) | 4.2 (1) | 7.7 (2) | 5 (14) | 13.2 (7) | 4.6 (29) |
| Orthopedic surgery | 0 | 0 | 0 | 7.7 (2) | 0.7 (2) | 0 (0) | 0.8 (5) |
| External institutions | 72.6 (127) | 50 (11) | 66.7 (16) | 57.7 (15) | 58.4 (163) | 49.1 (26) | 51.9 (329) |
| 4T score | |||||||
| Median | 4 | 5 | 4 | 5 | 4 | 5 | 4 |
| IQR | 4; 5 | 4; 6 | 4; 6 | 4; 6 | 3; 4 | 4; 6 | 3; 4 |
| Range (min./max.) | 3; 7 | 3; 7 | 3; 7 | 0; 7 | 0; 7 | 3; 8 | 0; 7 |
| ELISA, OD | |||||||
| Median | 0.04 | 1.98 | 0.63 | 1.50 | 0.06 | ||
| IQR | 0.02; 0.06 | 0.98; 2.49 | 0.41; 1.03 | 0.69; 2.39 | 0.04; 0.11 | NA | |
| Range (min./max.) | 0.00; 0.25 | 0.44; 3.00 | 0.32; 1.92 | 0.25; 3.00 | 0.01; 2.81 | ||
| CLIA, U/mL | |||||||
| Median | 11.53 | 0.08 | 4.56 | 0.03 | 11.8 | 0.02 | |
| IQR | NA | 1.63; 22.96 | 0.02; 0.13 | 1.34; 11.14 | 0.01; 0.05 | 3.60; 47.95 | 0.00; 0.07 |
| Range (min./max.) | 0.15; 52.49 | 0.01; 0.79 | 0.20; >128 | 0.00; 1.27 | 0.35; > 128 | 0.00; 12.11* | |
| PaGIA, titer | |||||||
| Median | 32 | 0 | 16 | 0 | 16 | 1† | |
| IQR | NA | 8; 32 | 0; 1 | 8; 32 | 0; 0 | 8; >16 | 0; 2 |
| Range (min./max.) | 4; 64 | 0; 8 | 2; 512 | 0; 8 | 2; >16 | 0; >16‡ | |
IQR, interquartile range; NA, not applicable (according to study design, ELISA was not performed in the prospective validation cohort); min./max., minimum/maximum.
Three patients had a CLIA result >3.0 U/mL and a negative HIPA: Patient PV-17.199, with CLIA 3.99 U/mL, low 4T score, and negative PaGIA is reported in Table 4; and Patients PV-19.014 and PV-19.232, with CLIA results of 4.36 and 12.11 U/mL, respectively, are described in supplemental Table 5.
n = 119 (PaGIA performed according to the algorithm depicted in Figure 2).
Three patients were recorded with a PaGIA titer ≥16 and a negative HIPA (PV-17.099, PV-18.123, and PV-19.111; they are described in supplemental Table 5).