RESUMO
BACKGROUND: A BRAF V600E mutation in papillary thyroid cancer (PTC) has been shown to be associated with aggressive behavior. Nevertheless, not all BRAF V600E PTCs behave aggressively. Allele frequency (AF) is the number of mutated molecules divided by the total number of wild-type molecules at a specific location in the genome. The relationship between BRAF V600E AF and the histopathological features of thyroid malignancies is not well understood. We hypothesized that the BRAF V600E AF will correlate directly with aggressive histopathological behavior. The aim of this study was to examine this relationship. METHODS: A retrospective chart review was performed for patients treated for BRAF V600E thyroid malignancies from 2019 to 2022 at McGill University tertiary care hospitals (n = 317). Patients with BRAF V600E-positive malignancies that included information on AF were included (n = 44). The correlation between AF and tumor histopathological features was analyzed. RESULTS: Out of the 44 nodules with a BRAF V600E mutation, those with aggressive features of PTC had a mean AF of 25.8%, which was significantly higher than the non-aggressive group with a mean AF of 10.25% (p = 0.020). Additionally, there was a statistically significant difference in mean AF between patients with a positive sentinel LN (29%) and those with a negative sentinel LN (17.8%) (p = 0.021). Classical PTC was present in 29.5% (13/44) of nodules, with a mean AF of 15.6%. The tall cell subtype was found in 64% (28/44) of nodules, with a mean AF of 23%. Solid and hobnail subtypes were less common in this study, and there was no statistically significant relationship between AF and histopathological subtypes (p = 0.107). Nodules smaller than 1cm had a mean AF of 13.3%, while nodules ranging from 1 2cm had a mean AF of 20.6%, and those larger than 2cm had a mean AF of 27.7%. However, no statistical difference was observed between AF and nodule size (p = 0.160). CONCLUSION: In this study, BRAF V600E mutations in conjunction with AF help to determine whether thyroid malignancies will display aggressive behavior. This pre-operative finding can help thyroid specialists to determine the extent of thyroidectomy and whether lymph node dissection is required.
RESUMO
INTRODUCTORY PARAGRAPHAs in many other settings, peak excess mortality preceded the officially reported first wave peak of the COVID-19 epidemic in Manaus, Brazil, reflecting delayed case recognition and limited initial access to diagnostic testing. To avoid early information bias, we used detailed age and gender stratified death certificate and hospitalisation data to evaluate the epidemics trajectory and infer the cause of its decline using a stochastic model. Our results are consistent with heterogenous transmission reducing over time due to the development of herd immunity. Relative to a baseline model that assumed homogenous mixing across Manaus, a model that permitted a small, self-isolated population fraction raised the estimated herd-immunity threshold from 28% to 30% and reduced the final attack rate from 86% to 65%. In the latter scenario, a substantial proportion of vulnerable, older individuals remained susceptible to infection. Given uncertainties regarding the distancing behaviours of population subgroups with different social and economic characteristics, and the duration of sterilising or transmission-modifying immunity in exposed individuals, we conclude that the potential for epidemic outbreaks remains, but that future waves of infection are likely to be much less pronounced than that already experienced.
