147 Diagnostic utility of molecular and imaging biomarkers 2 Table 22. Estimated pooled test performance of combined BRAF/RAS mutation analysis in indeterminate thyroid nodules ni test + (BRAF+) test + (RAS+) test - test ? nH (%) TP FP FN TN malignant (TP+FN/ni) sensitivity (95% CI), % specificity (95% CI), % LR+ (95% CI) LR- (95% CI) Cantara 2010 41 2 3 36 0 41 (100%) 4 1 3 33 17% 57 (18-90) 97 (85-100) 19.43 (2.54-148.63) 0.44 (0.19-1.04) Moses 2010 110 3 8 99 0 110 (100%) 7 4 22 77 26% 24 (10-44) 95 (88-99) 4.89 (1.54-15.48) 0.80 (0.65-0.99) Nikiforov 2011 461 7 53 401 0 461 (100%) 52 8 41 360 20% 56 (45-66) 98 (96-99) 25.72 (12.66-52.25) 0.45 (0.36-0.57) Mancini 2012 48 2 8 38 0 38 (79%) 4 3 5 26 19% 44 (14-79) 90 (73-98) 4.30 (1.17-15.71) 0.62 (0.34-1.13) Ohori 2013 424 7 50 327 40 384 (100%) 53 4 61 266 30% 46 (37-56) 99 (96-100) 31.38 (11.63-84.66) 0.54 (0.46-0.64) BeaudenonHuibregtse 2014 80 0 12 68 0 41 (51%) 8 2 9 22 21% 47 (23-72) 92 (73-99) 5.65 (1.37-23.35) 0.58 (0.36-0.92) Danilovic 2014 136 19 0 117 0 136 (100%) 19 0 11 106 22% 63 (44-80) 100 (97-100) 134.61 (8.36-2,166.59) 0.37 (0.24-0.59) Eszlinger 2014 (1) 164 0 15 126 23 141 (100%) 2 13 20 106 15% 9 (1-29) 89 (82-94) 0.83 (0.20-3.43) 1.02 (0.88-1.18) Eszlinger 2014 (2) 125 0 11 114 0 64 (51%) 1 4 8 51 7% 11 (0-48) 93 (82-98) 1.53 (0.19-12.17) 0.96 (0.75-1.22) Liu 2014 52 3 5 42 2 50 (100%) 4 4 4 38 16% 50 (16-84) 90 (77-97) 5.25 (1.64-16.77) 0.55 (0.27-1.11) Nikiforov 2014 143 2 24 117 0 143 (100%) 21 5 18 99 27% 54 (37-70) 95 (89-98) 11.20 (4.54-27.64) 0.48 (0.34-0.68) Eszlinger 2015 163 10 21 127 5 158 (100%) 22 9 23 104 28% 49 (34-64) 92 (85-96) 6.14 (3.07-12.29) 0.56 (0.42-0.74) Gill 2015 60 2 16 42 0 60 (100%) 10 8 13 29 38% 43 (23-66) 78 (62-90) 2.01 (0.93-4.34) 0.72 (0.49-1.07) Giovanella 2015 61 0 4 57 0 61 (100%) 3 1 13 44 26% 19 (4-46) 98 (88-100) 8.44 (0.94-75.40) 0.83 (0.65-1.06) Hwang 2015 564 57 47 453 7 86 (15%) 70 1 13 2 15% 84 (75-91) 67 (9-99) 2.53 (0.51-12.57) 0.23 (0.09-0.60) Le Mercier 2015 34 1 6 27 0 34 (100%) 5 2 2 25 21% 71 (29-96) 93 (76-99) 9.64 (2.35-39.63) 0.31 (0.10-1.00) Nikiforov 2015 462 2 17 443 0 95 (21%) 13 3 9 70 5% 59 (36-79) 96 (88-99) 14.38 (4.50-45.93) 0.43 (0.26-0.71) Rossi 2015 118 13 6 99 0 40 (34%) 14 4 4 18 15% 78 (52-94) 82 (60-95) 4.28 (1.70-10.74) 0.27 (0.11-0.66) Valderrabano 2016 105 0 13 90 2 56 (54%) 8 3 11 34 18% 42 (20-67) 92 (78-98) 5.19 (1.55-17.35) 0.63 (0.42-0.94) POOLED RESULTS 3,351 130 319 2,823 79 2,199 (67.2%) 320 79 290 1,510 18.2% 48.0 (37.7-58.5) 94.5 (91.7-96.4) 8.69 (5.41-13.96) 0.55 (0.45-0.68)
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