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IntroductionSamples classified as indeterminate correspond to 10-20% of cytologies obtained by fine needle biopsy of thyroid nodules, preventing an adequate distinction between benign and malignant lesions and leading to diagnostic thyroidectomies that often prove unnecessary, as most cases are benign. Furthermore, although the vast majority of patients with differentiated thyroid cancer (DTC) have such a good prognosis that active surveillance is permitted as an initial therapeutic option, relapses are not rare, and a non-negligible number of patients experience poor outcomes. MicroRNAs (miR) emerge as potential biomarkers capable of helping to define more precise management of patients in all these situations.MethodsAiming to investigate the clinical utility of miR-146b-5p in the diagnostic of thyroid nodules and evaluating its prognostic potential in a realworld setting, we studied 89 thyroid nodule samples, correlating miR-146b-5p expression with clinical tools such as the 8th edition from the American Joint Committee on Cancer (AJCC/UICC) and the American Thyroid Association Guideline Stratification Systems for the rate of recurrence (RR).ResultsmiR-146b-5p expression levels distinguished benign from malignant thyroid FNA samples (p< 0.0001). For indeterminate nodules, overexpression of miR-146b-5p with a cut-off of 0.497 was able to diagnose malignancy with a 90% accuracy; specificity=87.5%; sensitivity=100%. An increased expression of miR-146b-5p was associated with greater RR (p=0.015). A cut-off of 2.21 identified cases with more vascular involvement (p=0.013) and a cut-off of 2.420 was associated with a more advanced TNM stage (p-value=0.047).DiscussionWe demonstrated that miR-146b5p expression in FNA samples is able to differentiate benign from malignant indeterminate nodules and is associated with an increased risk of recurrence and mortality, suggesting that this single miRNA may be a useful diagnostic and prognostic marker in the personalized management of DTC patients.

Endocrine-disrupting and carcinogenic effects of glyphosate have long been suspected, but little is known about the effect of compounds used in real life at different concentrations, neither in normal nor in thyroid tumor cells. As cancer cells may have different sensitivities and the effect of the product containing glyphosate may be different from that produced by the active ingredient alone, including the Acceptable Occupational Exposure Level (AOEL=160µg/L) and the Acceptable Daily Intake (ADI=830µg/L) determined by ANVISA, we used two human thyroid-derived cell lines, Nthy-ori 3-1 (from normal follicular cells) and TPC-1 (from papillary carcinoma), to test 15 different concentrations of Roundup® Original DI. Trypan blue (TB), CCK-8 and BrdU assays were used to evaluate cytotoxicity, metabolic activity and proliferation with 24h and 48h exposures in technical and biological triplicates. TB showed an important toxic effect, especially after 24h of exposure, in both cell lines. The AOEL concentration caused the death of 43% and 50% of the Nthy-ori and TPC-1 cells, respectively, in 24 h, while ADI resulted in 35% and 58% of cell death. After 48h of exposure, AOEL and ADI caused a lower number of dead Nthy-ori (33% and 18%) and TPC-1 (33% and 37%) cells, respectively, suggesting that the toxic effect of the product disappears and/or both strains have repair mechanisms that protect them from longer exposures. On the other hand, the CCK-8 assay showed that small concentrations of Roundup have a proliferative effect: 6.5µg/L increased the number of both Nthy-ori and TPC-1 cells at 24h, and the BrdU assay confirmed the stimulatory effect with a 321% increase in the absorbance of Nthy-ori cells at 48h. The herbicide produced even more frequent increases in the BrdU absorbance of TPC-1 cells, mainly at 24h. We conclude that thyroid cells exposed to Roundup present a nonmonotonic dual dose–response curve. Low concentrations of the pesticide, considered acceptable, cause significant cell death but also have an important proliferative effect, especially on TPC-1 cells. This herbicide, widely used around the world, may play a role in the increased incidence rate of thyroid nodules and cancer that has been observed in recent decades.

ContextAlthough the overt hyperthyroidism treatment during pregnancy is mandatory, unfortunately, few studies have evaluated the impact of treatment on reducing maternal and fetal outcomes.ObjectiveThis study aimed to demonstrate whether treatment to control hyperthyroidism manifested during pregnancy can potentially reduce maternal-fetal effects compared with euthyroid pregnancies through a systematic review with meta-analysis.Data SourceMEDLINE (PubMed), Embase, Cochrane Library Central, LILACS/BIREME until May 2021.Study SelectionStudies that compared, during the gestational period, treated women with hyperthyroidism versus euthyroid women. The following outcomes of this comparison were: pre-eclampsia, abruptio placentae, fetal growth retardation, gestational diabetes, postpartum hemorrhage, low birth weight, stillbirth, spontaneous abortions, premature birth.Data ExtractionTwo independent reviewers extracted data and performed quality assessments. Dichotomous data were analyzed by calculating risk differences (DR) with fixed and random effect models according to the level of heterogeneity.Data SynthesisSeven cohort studies were included. The results of the meta-analysis indicated that there was a lower incidence of preeclampsia (p=0.01), low birth weight (p=0.03), spontaneous abortion (p

A better understanding of the SARS-CoV-2 virus behavior and possible risk factors implicated in poor outcome has become an urgent need. We performed a systematic review in order to investigate a possible association between body weight and prognosis among patients diagnosed with COVID-19. We searched in Cochrane Library, EMBASE, MEDLINE, WHO-Global Literature on Coronavirus Disease, OpenGrey, and Medrxiv. We used the ROBINS-I tool or Cross-Sectional/Prevalence Study Quality tool from AHRQ, to evaluate the methodological quality of included studies. Nine studies (two prospective cohorts, four retrospective cohorts and three cross-sectional) were included and assessed the relationship between obesity and COVID-19 prognosis. Risk of bias of the included studies ranged from moderate to critical. Clinical and methodological heterogeneity among them precluded meta-analyses. Most of the included studies showed some degree of association to: (a) higher BMI and worse clinical presentation and (b) obesity and need of hospitalization. The results were inconsistent about the impact of obesity on mortality. Based on limited methodological quality studies, obesity seems to predict poor clinical evolution in patients with COVID-19. Further studies with appropriate prospective design are needed to reduce the uncertainty on this evidence.

Background: Quality of life (QoL) studies in patients with mild to moderate Graves' orbitopathy (GO) are scarce.Methods: The original GO-QoL questionnaire was translated to Portuguese and administered to 323 patients with Graves' disease. The clinically active score (CAS) was used to evaluate GO activity, and the NO SPECS and EUGOGO classifications were used to estimate GO severity.Results: The internal consistency of the GO-QoL, evaluated using Cronbach's alpha, was optimal. In people with Graves' disease and long-duration GO, both visual function and appearance scores were negatively associated with the CAS and NOSPECS and EUGOGO classifications (P < 0.001). Asymmetry and proptosis were significantly associated with the visual function and appearance domains, and diplopia was related to the visual function score. In addition, multivariate regression stepwise analysis revealed that disease severity, according to the EUGOGO classification, was associated with the visual function and appearance scores; asymmetry, presence of proptosis, and young age were associated with the appearance score (P < 0.001). The visual function and appearance scores were negatively correlated with the CAS and NOSPECS and EUGOGO classifications (P < 0.001).Conclusion: Graves' orbitopathy has a negative impact in QoL in patients with mild to moderate disease, even after an extended period, rendering GO a chronic disease. The GO-QoL questionnaire can be helpful in identifying patients in need of attention and support.