The ultrasound risk stratification systems for thyroid nodule have been evaluated against papillary carcinoma. A meta-analysis

Thyroid imaging reporting and data systems (TIRADS) are used to stratify the malignancy risk of thyroid nodule by ultrasound (US) examination. We conducted a meta-analysis to evaluate the pooled cancer prevalence and the relative prevalence of papillary, medullary, follicular thyroid cancer (PTC, MTC, and FTC) and other malignancies among nodules included in studies evaluating their performance. Four databases were searched until February 2020. Original articles with at least 1000 nodules, evaluating the performance of at least one TIRADS among AACE/ACE/AME, ACR-TIRADS, ATA, EU-TIRADS, or K-TIRADS, and reporting data on the histological diagnosis of malignant lesions were included. The number of malignant nodules, PTC, FTC, MTC and other malignancies in each study was extracted. For statistical pooling of data, a random-effects model was used. Nine studies were included, evaluating 19,494 thyroid nodules. The overall prevalence of malignancy was 34% (95%CI 21 to 49). Among 6162 histologically proven malignancies, the prevalence of PTC, FTC, MTC and other malignancies was 95%, 2%, 1%, and 1%, respectively. A high heterogeneity was found for all the outcomes. A limited number of studies generally conducted using a retrospective design was found, with possible selection bias. Acknowledging this limitation, TIRADSs should be regarded as accurate tools to diagnose PTC only. Proposed patterns and/or cut-offs should be revised and other strategies considered to improve their performance in the assessment of FTC, MTC and other malignancies

Nodular Thyroid Disease in the Era of Precision Medicine

Management of thyroid nodules in the era of precision medicine is continuously changing. Neck ultrasound plays a pivotal role in the diagnosis and several ultrasound stratification systems have been proposed in order to predict malignancy and help clinicians in therapeutic and follow-up decision. Ultrasound elastosonography is another powerful diagnostic technique and can be an added value to stratify the risk of malignancy of thyroid nodules. Moreover, the development of new techniques in the era of "Deep Learning," has led to a creation of machine-learning algorithms based on ultrasound examinations that showed similar accuracy to that obtained by expert radiologists. Despite new technologies in thyroid imaging, diagnostic surgery in 50-70% of patients with indeterminate cytology is still performed. Molecular tests can increase accuracy in diagnosis when performed on "indeterminate" nodules. However, the more updated tools that can be used to this purpose in order to "rule out" (Afirma GSC) or "rule in" (Thyroseq v3) malignancy, have a main limitation: the high costs. In the last years various image-guided procedures have been proposed as alternative and less invasive approaches to surgery for symptomatic thyroid nodules. These minimally invasive techniques (laser and radio-frequency ablation, high intensity focused ultrasound and percutaneous microwave ablation) results in nodule shrinkage and improvement of local symptoms, with a lower risk of complications and minor costs compared to surgery. Finally, ultrasound-guided ablation therapy was introduced with promising results as a feasible treatment for low-risk papillary thyroid microcarcinoma or cervical lymph node metastases

Prediction of response to vemurafenib in BRAF V600E mutant cancers based on a network approach

Lung adenocarcinoma is the tumor with the highest number of switch genes (298) compared to its normal tissue, followed by thyroid (227) and colorectal (183) cancers. Switch genes codifying for kinases were 14,7 and 3 respectively.We looked for three homology sequences identified across vemurafenib targets and we found that thyroid cancer and lung adenocarcinoma have a similar number of putative targetable switch genes kinase (5-6); on the contrary, colorectal cancer has just one,with minor homology sequence

Does the site of origin of the microcarcinoma with respect to the thyroid surface matter? A multicenter pathologic and clinical study for risk stratification

It is unclear whether the site of origin of papillary thyroid microcarcinoma (mPTC) with respect to the thyroid surface has an influence on clinicopathologic parameters. The objectives of the study were to: (i) Accurately measure the mPTC distance from the thyroid surface; (ii) analyze whether this distance correlates with relevant clinicopathologic parameters; and (iii) investigate the impact of the site of origin of the mPTC on risk stratification. Clinicopathologic features and BRAF mutational status were analyzed and correlated with the site of origin of the mPTC in a multicenter cohort of 298 mPTCs from six Italian medical institutions. Tumors arise at a median distance of 3.5 mm below the surface of the thyroid gland. Statistical analysis identified four distinct clusters. Group A, mPTC: size 65 5 mm and distance of the edge of the tumor from the thyroid capsule = 0 mm; group B, mPTC: size 65 5 mm and distance of the edge of the tumor from the thyroid capsule > 0 mm; group C, mPTC: size < 5 mm and distance of the edge of the tumor from the thyroid capsule = 0 mm; and group D, mPTC: size < 5 mm and distance of the edge of the tumor from the thyroid capsule > 0 mm. Univariate analysis demonstrates significant differences between the groups: Group A shows the most aggressive features, and group D the most indolent ones. By multivariate analysis, group A tumors are characterized by tall cell histotype, BRAF V600E mutation, tumor fibrosis, aggressive growth with invasive features, vascular invasion, lymph node metastases, and intermediate ATA risk. The mPTC clinicopathologic features vary according to the tumor size and distance from the thyroid surface. A four-group model may be useful for risk stratification and to refine the selection of nodules to be targeted for fine needle aspiration

Artificial Intelligence for Thyroid Nodule Characterization: Where Are We Standing?

Machine learning (ML) is an interdisciplinary sector in the subset of artificial intelligence (AI) that creates systems to set up logical connections using algorithms, and thus offers predictions for complex data analysis. In the present review, an up-to-date summary of the current state of the art regarding ML and AI implementation for thyroid nodule ultrasound characterization and cancer is provided, highlighting controversies over AI application as well as possible benefits of ML, such as, for example, training purposes. There is evidence that AI increases diagnostic accuracy and significantly limits inter-observer variability by using standardized mathematical algorithms. It could also be of aid in practice settings with limited sub-specialty expertise, offering a second opinion by means of radiomics and computer-assisted diagnosis. The introduction of AI represents a revolutionary event in thyroid nodule evaluation, but key issues for further implementation include integration with radiologist expertise, impact on workflow and efficiency, and performance monitoring

Key processes for Cheirolophus (Asteraceae) diversification on oceanic islands inferred from AFLP data

The radiation of the genus Cheirolophus (Asteraceae) in Macaronesia constitutes a spectacular case of rapid diversification on oceanic islands. Twenty species - nine of them included in the IUCN Red List of Threatened Species - have been described to date inhabiting the Madeiran and Canarian archipelagos. A previous phylogenetic study revealed that the diversification of Cheirolophus in Macaronesia started less than 2 Ma. As a result of such an explosive speciation process, limited phylogenetic resolution was reported, mainly due to the low variability of the employed molecular markers. In the present study, we used highly polymorphic AFLP markers to i) evaluate species' boundaries, ii) infer their evolutionary relationships and iii) investigate the patterns of genetic diversity in relation to the potential processes likely involved in the radiation of Cheirolophus. One hundred and seventy-two individuals representing all Macaronesian Cheirolophus species were analysed using 249 AFLP loci. Our results suggest that geographic isolation played an important role in this radiation process. This was likely driven by the combination of poor gene flow capacity and a good ability for sporadic long-distance colonisations. In addition, we also found some traces of introgression and incipient ecological adaptation, which could have further enhanced the extraordinary diversification of Cheirolophus in Macaronesia. Last, we hypothesize that current threat categories assigned to Macaronesian Cheirolophus species do not reflect their respective evolutionary relevance, so future evaluations of their conservation status should take into account the results presented here

Low extracellular vesicle concentrations predict survival in patients with heart failure

BackgroundHeart disease is of worldwide importance due to high morbidity and mortality. Extracellular vesicle (EV) concentration and size represent novel diagnostic and prognostic biomarkers, e.g. in patients with liver cancer, but data on their prognostic relevance in heart disease are lacking. Here, we investigated the role of EV concentration, size and zeta potential in patients with heart disease.MethodsVesicle size distribution, concentration and zeta potential were measured by nanoparticle tracking analysis (NTA) in 28 intensive care unit (ICU) and 20 standard care (SC) patients and 20 healthy controls.ResultsPatients with any disease had a lower zeta potential compared to the healthy controls. Vesicle size (X50) was significantly higher in ICU patients (245 nm) with heart disease as compared to those patients with heart disease receiving standard care (195 nm), or healthy controls (215 nm) (p = 0.001). Notably, EV concentration was lower in ICU patients with heart disease (4.68 × 1010 particles/ml) compared to SC patients with heart disease (7,62 × 1010 particles/ml) and healthy controls (1.50 × 1011 particles/ml) (p = 0.002). Extracellular vesicle concentration is prognostic for overall survival in patients with heart disease. Overall survival is significantly reduced when the vesicle concentration is below 5.55 × 1010 particles/ml. Median overall survival was only 140 days in patients with vesicle concentrations below 5.55 × 1010 particles/ml compared to 211 days in patients with vesicle concentrations above 5.55 × 1010 particles/ml (p = 0.032).SummaryConcentration of EVs is a novel prognostic marker in ICU and SC patients with heart disease

GMP-selected dual and lensed AGNs: selection function and classification based on near-IR colors and resolved spectra from VLT/ERIS, KECK/OSIRIS, and LBT/LUCI

The Gaia-Multi-Peak (GMP) technique can be used to identify large numbers of dual or lensed AGN candidates at sub-arcsec separation, allowing us to study both multiple SMBHs in the same galaxy and rare, compact lensed systems. The observed samples can be used to test the predictions of the models of SMBH merging once 1) the selection function of the GMP technique is known, and 2) each system has been classified as dual AGN, lensed AGN, or AGN/star alignment. Here we show that the GMP selection is very efficient for separations above 0.15'' when the secondary (fainter) object has magnitude G<20.5. We present the spectroscopic classification of five GMP candidates using VLT/ERIS and Keck/OSIRIS, and compare them with the classifications obtained from: a) the near-IR colors of 7 systems obtained with LBT/LUCI, and b) the analysis of the total, spatially-unresolved spectra. We conclude that colors and integrated spectra can already provide reliable classifications of many systems. Finally, we summarize the confirmed dual AGNs at z>0.5 selected by the GMP technique, and compare this sample with other such systems from the literature, concluding that GMP can provide a large number of confirmed dual AGNs at separations below 7 kpc.Comment: 14 pages,A&A, in pres

Minimal Extrathyroidal Extension in Predicting 1-Year Outcomes: A Longitudinal Multicenter Study of Low-to-Intermediate-Risk Papillary Thyroid Carcinoma (ITCO#4)

Background: The role of minimal extrathyroidal extension (mETE) as a risk factor for persistent papillary thyroid carcinoma (PTC) is still debated. The aims of this study were to assess the clinical impact of mETE as a predictor of worse initial treatment response in PTC patients and to verify the impact of radioiodine therapy after surgery in patients with mETE. Methods: We reviewed all records in the Italian Thyroid Cancer Observatory database and selected 2237 consecutive patients with PTC who satisfied the inclusion criteria (PTC with no lymph node metastases and at least 1 year of follow-up). For each case, we considered initial surgery, histological variant of PTC, tumor diameter, recurrence risk class according to the American Thyroid Association (ATA) risk stratification system, use of radioiodine therapy, and initial therapy response, as suggested by ATA guidelines. Results: At 1-year follow-up, 1831 patients (81.8%) had an excellent response, 296 (13.2%) had an indeterminate response, 55 (2.5%) had a biochemical incomplete response, and 55 (2.5%) had a structural incomplete response. Statistical analysis suggested that mETE (odds ratio [OR] 1.16, p = 0.65), tumor size &gt;2 cm (OR 1.45, p = 0.34), aggressive PTC histology (OR 0.55, p = 0.15), and age at diagnosis (OR 0.90, p = 0.32) were not significant risk factors for a worse initial therapy response. When evaluating the combination of mETE, tumor size, and aggressive PTC histology, the presence of mETE with a &gt;2 cm tumor was significantly associated with a worse outcome (OR 5.27 [95% confidence interval], p = 0.014). The role of radioiodine ablation in patients with mETE was also evaluated. When considering radioiodine treatment, propensity score-based matching was performed, and no significant differences were found between treated and nontreated patients (p = 0.24). Conclusions: This study failed to show the prognostic value of mETE in predicting initial therapy response in a large cohort of PTC patients without lymph node metastases. The study suggests that the combination of tumor diameter and mETE can be used as a reliable prognostic factor for persistence and could be easily applied in clinical practice to manage PTC patients with low-to-intermediate risk of recurrent/persistent disease