Background: Molecular tests are being used increasingly as an auxiliary diagnostic tool so as to avoid a diagnostic surgery approach for cytologically indeterminate thyroid nodules (ITNs). Previous test versions, Thyroseq v2 and Afirma Gene Expression Classifier (GEC), have proven shortcomings in malignancy detection performance.Objective: This study aimed to evaluate the diagnostic performance of the established Thyroseq v3, Afirma Gene Sequencing Classifier (GSC), and microRNA-based assays versus prior iterations in ITNs, in light of “rule-in” and “rule-out” concepts. It further analyzed the impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) reclassification and Bethesda cytological subtypes on the performance of molecular tests.Methods: Pubmed, Scopus, and Web of Science were the databases used for the present research, a process that lasted until September 2020. A random-effects bivariate model was used to estimate the summary sensitivity, specificity, positive (PLR) and negative likelihood ratios (NLR), and area under the curve (AUC) for each panel. The conducted sensitivity analyses addressed different Bethesda categories and NIFTP thresholds.Results: A total of 40 eligible studies were included with 7,831 ITNs from 7,565 patients. Thyroseq v3 showed the best overall performance (AUC 0.95; 95% confidence interval: 0.93–0.97), followed by Afirma GSC (AUC 0.90; 0.87–0.92) and Thyroseq v2 (AUC 0.88; 0.85–0.90). In terms of “rule-out” abilities Thyroseq v3 (NLR 0.02; 95%CI: 0.0–2.69) surpassed Afirma GEC (NLR 0.18; 95%CI: 0.10–0.33). Thyroseq v2 (PLR 3.5; 95%CI: 2.2–5.5) and Thyroseq v3 (PLR 2.8; 95%CI: 1.2–6.3) achieved superior “rule-in” properties compared to Afirma GSC (PLR 1.9; 95%CI: 1.3–2.8). Evidence for Thyroseq v3 seems to have higher quality, notwithstanding the paucity of studies. Both Afirma GEC and Thyroseq v2 performance have been affected by NIFTP reclassification. ThyGenNEXT/ThyraMIR and RosettaGX show prominent preliminary results.Conclusion: The newly emerged tests, Thyroseq v3 and Afirma GSC, designed for a “rule-in” purpose, have been proved to outperform in abilities to rule out malignancy, thus surpassing previous tests no longer available, Thyroseq 2 and Afirma GEC. However, Thyroseq v2 still ranks as the best rule-in molecular test.Systematic Review Registration: http://www.crd.york.ac.uk/PROSPERO, identifier CRD42020212531.

Background: Virtual reality (VR) may enhance the effectiveness of psychological interventions for acute pain. We conducted a meta-analysis to assess the efficacy and safety of VR-based interventions for pain associated with medical procedures.Methods: We searched PubMed, EMBASE, the Cochrane Library, and PsycINFO until June 17th 2018. We identified randomized controlled trials (RCTs), comparing VR-based psychological interventions to usual care, for pain intensity (primary outcome) or affective and cognitive components of pain (secondary outcomes), assessed real-time or retrospectively. Two independent reviewers performed study selection and data extraction. Risk of bias was independently evaluated by three raters using the revised Cochrane Collaboration tool. A random-effects model using the Paule and Mandel estimator was used for pooling effect sizes.Results: 27 RCTs (1452 patients) provided enough data for meta-analysis. Compared to usual care, VR-based interventions reduced pain intensity both real-time (9 RCTs, Hedges' g = 0.95, 95% CI 0.32–1.57) and retrospectively (22 RCTs, g = 0.87, 95% CI 0.54–1.21). Results were similar for cognitive (8 RCTs, g = 0.82, 95% CI 0.39–1.26) and affective pain components (14 RCTs, g = 0.55, 95% CI 0.34–0.77). There was marked heterogeneity, which remained similarly high in sensitivity analyses. Across domains, few trials were rated as low risk of bias and there was evidence of publication bias. Adverse events were rare.Conclusions: Though VR-based interventions reduced pain for patients undergoing medical procedures, inferring clinical effectiveness is precluded by the predominance of small trials, with substantial risk of bias, and by incomplete reporting.

Thyroid cancer (TC) includes various phenotypes, from indolent to highly aggressive cancer. The limitations of the current prognostication systems to predict the recurrence risk and the variability in expression of the genes involved in the thyroid carcinogenesis uncover the need for new prognostic biomarkers by taking into account potential epigenetic differences. We aimed to summarize the current knowledge regarding the prognostic impact of microRNAs (miRNAs) in TC. A literature search was conducted in PubMed, Embase, Scopus, and Web of Science databases. Both upregulated and downregulated miRNAs are significantly correlated with worse overall survival (hazard ratio (HR) = 5.94, 95% CI: 2.73–12.90, p < 0.001; HR = 0.51, 95% CI: 0.26–0.96, p = 0.048) disease/recurrence-free survival (HR = 1.58, 95% CI: 1.08–2.32, p = 0.003; HR = 0.37, 95%, CI: 0.24–0.60, p < 0.001). Sensitivity analysis revealed a significant association between the higher expression of miR-146b, miR-221, and miR-222 and the recurrence of papillary TC (OR = 9.11, 95% CI 3.00 to 27.52; p < 0.001; OR = 3.88, 95% CI 1.34 to 11.19, p < 0.001; OR = 6.56, 95% CI 2.75 to 15.64, p < 0.001). This research identified that miR-146b, miR-221, and miR-222 could serve as potential prognostic biomarkers in TC, particularly in PTC. Further studies are needed to strengthen these findings and sustain its clinical applicability.