80 chapter 2 Figure 1. Systematic literature search PubMed n = 9,678 Embase n = 11,502 Cochrane n = 175 identified citations using search strategy n = 21,355 titles and abstracts screened for relevance n = 15,534 removal of duplicates (n = 5,821) full-text articles retreived and screened for eligibility n = 750 Inclusion criteria: • study domain: thyroid nodules with indeterminate cytology • index test: any additional diagnostic techniques • reference standard: histopathology • original studies Exclusion criteria: • publication type: review/metaanalyses, letter to the editor, author commentaries, opinion papers, case reports, case-control studies • <10 patients with indeterminate cytology • non-human studies • non-adult • article written in language other than English, French, German or Dutch • studies on ex-vivo FNA samples • overlapping patient populations • data for indeterminate thyroid nodules not extractable additional articles identified by cross-reference check (n = 1) unique original articles included in systematic review and meta-analysis n = 164 articles suitable for ≥2* major topics (n = 19) selected full-text articles n = 164 * one article was included for four major topics. **: combination of determinants investigated within the same major topic. FDG-PET n = 11 99mTc-MIBI n = 3 DW-MRI n = 1 CT n = 0 ultrasound n = 56 elastosonography n = 14 mutation analysis n = 75 immunocytochemistry n = 19 microRNA n = 6 quality and applicability assessment (QUADAS-2) n = 165 BRAF (n = 52) RAS (n = 20) RET/PTC (n = 17) PAX8/PPARy (n = 13) combination** (n = 16) other (n = 7) miRInform® (n = 5) NGS (n = 3) Afirma® GEC (n = 13) Galectin-3 (n = 12) HBME-1 (n = 7) CK-19 (n = 3) combination** (n =11 ) other (n = 9) Data extraction n = 165 exclusion of study without benign histopathology results (n = 1)
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