Increasing diagnostic effectiveness of thyroid nodule evaluation by implementation of cell block preparation in routine US-FNA analysis

Objective: Ultrasound-guided fine-needle aspiration (US-FNA) biopsy has proven to be an accurate and efficient tool in thyroid nodule evaluation. We evaluated whether cell block adds to the diagnostic accuracy of US-FNA. Subjects and methods: Three hundred twenty-eight consecutive patients underwent US-FNA, cytology and cell block evaluation. Six slides were prepared for each patient and stained by Papanicolaou and Giemsa techniques. The residual hemorrhagic aspirate in the syringe and needle was fixed in 10% formalin and paraffin-embedded (cell block). The histological sections were examined as a complementary diagnostic tool to US-FNA. Results: The study population comprised 89% females and the mean age was 57.4 ± 13.7 years. The mean nodule size was 2.3 ± 1.2 cm. US-FNA cytological results were as follows: Bethesda I, 17.1% (n = 56); Bethesda II, 61.6% (n = 202); Bethesda III, 9.5% (n = 31); Bethesda IV, 5.8% (n = 19); Bethesda V, 2.4% (n = 8), and Bethesda VI, 3.6% (n = 12). Cell blocks were obtained in 100% of cases and were considered diagnostic in 89.6%. Combined cytological and cell block (cyto-cell block) results were as follows: unsatisfactory, 4.3% (n = 14); benign, 72.6% (n = 238); indeterminate, 11.3% (n = 37); follicular lesion, 5.8% (n = 19); suspicious for malignancy, 2.4% (n = 8), and malignant, 3.6% (n = 12). The sensitivity and specificity for cyto-cell block was 100% and 90%, respectively, and the accuracy was 94%. Cyto-cell block analysis reduced the rate of unsatisfactory samples (p < 0.001). Conclusions: The cyto-cell block interpretation improved the efficiency of US-FNA. This simple, fast and low-cost technique should be used as an adjunctive test in thyroid nodule evaluation

Neoadjuvant multikinase inhibitor in patients with locally advanced unresectable thyroid carcinoma

Background: Papillary thyroid carcinoma (PTC) is the most common and less aggressive thyroid cancer, but some patients may display locally advanced disease. Therapeutic options are limited in these cases, particularly for those patients with unresectable tumors. Neoadjuvant therapy is not part of the recommended work up. Methods: Report a case of an unresectable grossly locally invasive PTC successfully managed with neoadjuvant therapy and provide a systematic review (SR) using the terms “Neoadjuvant therapy” AND “Thyroid carcinoma.” Results: A 32-year-old man with a 7.8 cm (in the largest dimension) PTC was referred to total thyroidectomy, but tumor resection was not feasible due to extensive local invasion (trachea, esophagus, and adjacent structures). Sorafenib, a multikinase inhibitor (MKI), was initiated; a 70% tumor reduction was observed after 6 months, allowing new surgical intervention and complete resection. Radioactive iodine (RAI) was administered as adjuvant therapy, and whole body scan (WBS) shows uptake on thyroid bed. One-year post-surgery the patient is asymptomatic with a status of disease defined as an incomplete biochemical response. The SR retrieved 123 studies on neoadjuvant therapy use in thyroid carcinoma; of them, 6 were extracted: 4 case reports and 2 observational studies. MKIs were used as neoadjuvant therapy in three clinical cases with 70–84% of tumor reduction allowing surgery. Conclusion: Our findings, along with other reports, suggest that MKIs is an effective neoadjuvant therapy and should be considered as a therapeutic strategy for unresectable grossly locally invasive thyroid carcinomas

Brazilian consensus on the treatment of fibromyalgia

UNIFESP Ambulatório de FibromialgiaUFPR HC ambulatório de fibromialgiaUNIFESPUNIFESP Setor de reumatismos de partes molesPUC-SP Departamento de MedicinaPUC-Campinas Hospital Universitário Serviço de ReumatologiaSociedade Brasileira de ReumatologiaSanta Casa de Belo Horizonte Ambulatório de Fibromialgia Programa de Residência Médica em ReumatologiaFMUSP HC Serviço de ReumatologiaSanta Casa de Campo Grande Setor de Reumatologia programa de Residência em Clínica MédicaUniversidade Federal de Ciências da Saúde de Porto AlegreUNiSULUniversidade Federal do Espírito Santo Hospital Universitário serviço de ReumatologiaSociedade Brasileira de Clínica MédicaSociedade Brasileira para o Estudo da DorAssociação Brasileira de Medicina Física e ReabilitaçãoUniversidade de São Paulo Faculdade de MedicinaUniversidade Federal FluminenseAcademia Brasileira de Neurologia Departamento de DorEuropean Neurological Society Subcomitê de DorPeripheral Nerve SocietyFMUSP Grupo de MãoSociedade Brasileira de ortopedia e TraumatologiaAxia.Bio farmacoeconomia e pesquisa em saúdeUNIFESP Núcleo de Gestão de PesquisasUNIFESP, Ambulatório de FibromialgiaUNIFESP, Setor de reumatismos de partes molesUNIFESP, Núcleo de Gestão de PesquisasSciEL

Worldwide trends in underweight and obesity from 1990 to 2022 : a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

A list of authors and their affiliations appears online. A supplementary appendix is herewith attached.Background: Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods: We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI 2 SD above the median). Findings: From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation: The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesity.peer-reviewe

Avaliação do TSH sérico como fator preditivo de malignidade em nódulos tireoidianos de pacientes submetidos à punção aspirativa por agulha fina

Nódulos de tireoide são achados clínicos comuns e, atualmente, o método diagnóstico de escolha para diferenciar lesões benignas de lesões malignas é a análise citopatológica dos nódulos através de punção aspirativa por agulha fina (PAAF). Estudos prévios já indicaram que os níveis séricos de TSH podem estar associados ao risco de malignidade nodular. O objetivo deste estudo foi avaliar se o TSH sérico é um preditor de malignidade em nódulos de tireoide em pacientes submetidos à PAAF. A amostra contemplou 100 indivíduos puncionados consecutivamente no Centro de Pronto Diagnóstico Ambulatorial, CPDA, HCPA e que apresentavam níveis de TSH dentro da normalidade. Todos os pacientes foram submetidos à PAAF da tireoide com controle ultrassonográfico e tiveram, posteriormente, a análise citopatológica da PAAF e a avaliação histopatológica do bloco celular. A análise estatística baseou-se em dados de frequências e testes não-paramétricos foram utilizados para correlacionar as variáveis. A população de estudo foi composta por 100 pacientes, sendo 89 mulheres e 11 homens. A média de idade foi de 54,1 ± 14,2 anos e o tamanho médio dos nódulos foi de 2.53 ± 1.36 centímetros. Vinte e seis % destes pacientes apresentavam algum tipo de doença tireoidiana prévia. A média do nível de TSH sérico entre os 100 indivíduos foi de 1.81 ± 1.08 uUI/mL. De acordo com o diagnóstico citopatológico da PAAF complementado pelos achados do bloco celular foram classificados como malignos 8% dos nódulos, 70% benignos, 11% suspeitos/ indeterminados, 8% insuficientes e 3% lesões foliculares. A média de TSH para os grupos maligno, benigno, suspeito/indeterminado, insuficiente e lesão folicular foi de, respectivamente, 2.48, 1.59, 2.21, 2.35 e 2.20 uUI/ml (p>0.05). Não houve diferença estatística significante entre os grupos diagnósticos avaliados, apesar de haver uma variação entre os níveis de TSH entre os grupos refletindo, provavelmente, o pequeno tamanho da amostra.Thyroid nodules are common and currently the first choice of investigation in distinguishing benign from malignant disease is the cytological analysis of fine needle aspiration biopsy (FNAB). Previous studies have indicated that serum TSH levels might be associated with the likelihood of malignancy. The aim of this study was to evaluate whether serum TSH is a predictor of malignancy of thyroid nodules in patients undergoing FNAB. One hundred consecutive patients, who underwent FNAB as part of clinical investigation of thyroid nodule in a multidisciplinary setting tertiary hospital, underwent ultrasonography followed by FNAB, cytology and cell block analysis. Independent-Samples Kruskal-Wallis test was used to compare the groups. The study population comprised of 89 female and 11 male patients. The mean age was 54.1 ± 14.2 years. 26% had previous thyroid disease. Mean TSH levels was 1.81 ± 1.08 uUI/mL and the mean nodule size was 2.53 ± 1.36cm. Final cytology/cell block diagnosis classified 8% as malignant, 70% as benign, 11% suspicious/indeterminate, 8% insufficient and 3% follicular lesion. The mean TSH values for malignant, benign, suspect, insufficient and follicular lesion group were as follows: 2.48, 1.59, 2.21, 2.35 and 2.20 uUI/ml, respectively. No statistical significance was detected between TSH levels and final cytology/cell block diagnosis, possibly reflecting the small sample size (P>0.05). We observed a variation between TSH levels among the groups covered in this study, but there was no statistically significant difference among them

Avaliação do TSH sérico como fator preditivo de malignidade em nódulos tireoidianos de pacientes submetidos à punção aspirativa por agulha fina

Nódulos de tireoide são achados clínicos comuns e, atualmente, o método diagnóstico de escolha para diferenciar lesões benignas de lesões malignas é a análise citopatológica dos nódulos através de punção aspirativa por agulha fina (PAAF). Estudos prévios já indicaram que os níveis séricos de TSH podem estar associados ao risco de malignidade nodular. O objetivo deste estudo foi avaliar se o TSH sérico é um preditor de malignidade em nódulos de tireoide em pacientes submetidos à PAAF. A amostra contemplou 100 indivíduos puncionados consecutivamente no Centro de Pronto Diagnóstico Ambulatorial, CPDA, HCPA e que apresentavam níveis de TSH dentro da normalidade. Todos os pacientes foram submetidos à PAAF da tireoide com controle ultrassonográfico e tiveram, posteriormente, a análise citopatológica da PAAF e a avaliação histopatológica do bloco celular. A análise estatística baseou-se em dados de frequências e testes não-paramétricos foram utilizados para correlacionar as variáveis. A população de estudo foi composta por 100 pacientes, sendo 89 mulheres e 11 homens. A média de idade foi de 54,1 ± 14,2 anos e o tamanho médio dos nódulos foi de 2.53 ± 1.36 centímetros. Vinte e seis % destes pacientes apresentavam algum tipo de doença tireoidiana prévia. A média do nível de TSH sérico entre os 100 indivíduos foi de 1.81 ± 1.08 uUI/mL. De acordo com o diagnóstico citopatológico da PAAF complementado pelos achados do bloco celular foram classificados como malignos 8% dos nódulos, 70% benignos, 11% suspeitos/ indeterminados, 8% insuficientes e 3% lesões foliculares. A média de TSH para os grupos maligno, benigno, suspeito/indeterminado, insuficiente e lesão folicular foi de, respectivamente, 2.48, 1.59, 2.21, 2.35 e 2.20 uUI/ml (p>0.05). Não houve diferença estatística significante entre os grupos diagnósticos avaliados, apesar de haver uma variação entre os níveis de TSH entre os grupos refletindo, provavelmente, o pequeno tamanho da amostra.Thyroid nodules are common and currently the first choice of investigation in distinguishing benign from malignant disease is the cytological analysis of fine needle aspiration biopsy (FNAB). Previous studies have indicated that serum TSH levels might be associated with the likelihood of malignancy. The aim of this study was to evaluate whether serum TSH is a predictor of malignancy of thyroid nodules in patients undergoing FNAB. One hundred consecutive patients, who underwent FNAB as part of clinical investigation of thyroid nodule in a multidisciplinary setting tertiary hospital, underwent ultrasonography followed by FNAB, cytology and cell block analysis. Independent-Samples Kruskal-Wallis test was used to compare the groups. The study population comprised of 89 female and 11 male patients. The mean age was 54.1 ± 14.2 years. 26% had previous thyroid disease. Mean TSH levels was 1.81 ± 1.08 uUI/mL and the mean nodule size was 2.53 ± 1.36cm. Final cytology/cell block diagnosis classified 8% as malignant, 70% as benign, 11% suspicious/indeterminate, 8% insufficient and 3% follicular lesion. The mean TSH values for malignant, benign, suspect, insufficient and follicular lesion group were as follows: 2.48, 1.59, 2.21, 2.35 and 2.20 uUI/ml, respectively. No statistical significance was detected between TSH levels and final cytology/cell block diagnosis, possibly reflecting the small sample size (P>0.05). We observed a variation between TSH levels among the groups covered in this study, but there was no statistically significant difference among them

Marcadores prognósticos nas neoplasias de tireoide

Nódulos tireoidianos são achados clínicos comuns. O câncer de tireoide, em contraste, é raro, embora consista na neoplasia endócrina maligna mais frequente. Um dos principais desafios no manejo de pacientes com neoplasias de tireoide é identificar, além dos parâmetros clínicos, características morfológicas e alterações moleculares capazes de diferenciar tumores que se comportarão de forma mais agressiva. A identificação de marcadores prognósticos confiáveis que determinem já ao diagnóstico, o comportamente biológico do tumor poderá evitar que pacientes de baixo risco sejam expostos a condutas agressivas desnecessárias, e distinguir estes pacientes daqueles que, por apresentarem evolução menos favorável, necessitem de cirurgias mais extensas e acompanhamento mais intenso. Com os avanços no conhecimento da patogênese das neoplasias tireoidianas, inúmeros estudos vêm investigando marcadores preditivos e prognósticos em relação aos tumores da tireoide, possibilitando o desenvolvimento de novos agentes antineoplásicos. Dessa forma, a tendência na atualidade é de que o tratamento seja feito de forma mais individualizada, considerando o quadro clínico e marcadores, morfológicos, imunohistoquímicos e moleculares do paciente e do tumor. A primeira parte desta tese compreende uma avaliação prospectiva do papel dos níveis de hormônio tireotrófico (TSH) como preditores de malignidade em nódulos da tireoide em uma amostra de 615 pacientes submetidos à punção aspirativa por agulha fina (PAAF) guiada por ultrassom. O TSH é um fator de crescimento essencial para as células da tireoide e sua via de sinalização é necessária para a expressão de outros fatores de crescimento, receptores e proto-oncogenes. Consequentemente, a supressão do TSH é importante para o manejo clínico do câncer de tireoide. De modo interessante, observamos que níveis séricos mais altos de TSH foram associados a um risco aumentado de malignidade. Pacientes com nódulos malignos apresentaram TSH sérico mais elevado que pacientes com nódulos benignos nos dois ensaios analisados (2.25 vs. 1.50; P = 0.04 e 2.33 vs. 1.27; P = 0.03) e o risco de malignidade foi aproximadamente três vezes maior em pacientes com níveis de TSH ≥ 2.26μU/mL do que em pacientes com níveis mais baixos de TSH. Nossos resultados corroboram estudos prévios que sugerem o uso do TSH como ferramenta diagnóstica auxiliar na estratificação do risco de malignidade associado a nódulos tireoidianos bem como na tomada de decisão da conduta terapêutica. A segunda parte deste trabalho, por sua vez, avaliou em uma coorte de 420 pacientes com carcinoma medular de tireoide (CMT), o papel de polimorfismos de nucleotídeo único (SNPs) do gene VEGF-A na patogênese da doença através da correlação das frequências das variantes com dados clínicos, laboratoriais e prognóstico. Sabe-se que em diversos tumores, incluindo o CMT, há uma superexpressão do VEGF-A e seus receptores, o que possibilita utilizá-los como alvos moleculares para terapias com inibidores multiquinase (MKI) e também como marcadores prognósticos. Os SNPs do VEGF-A rs699947 (C> A), rs833061 (T C) foram genotipados usando ensaio de TaqMan e os haplótipos foram inferidos usando o programa Phase. 202 (48%) pacientes apresentaram a forma hereditária e 218 (52%) apresentaram a forma esporádica do CMT. A idade média do diagnóstico foi de 40 ± 19.7 anos e 61% eram do sexo feminino. As freqüências alélicas dos SNPs do VEGF-A foram: rs699947 (37.2%), rs833061 (45.6%) e rs2010963 (34.4%). No CTM hereditário, observamos uma associação independente do VEGF-A rs833061 com menor idade ao diagnóstico (genótipo TT) e menor tamanho do tumor (genótipo CC). Além disso, o VEGF-A rs2010963 (genótipo GG) foi associado com menor tamanho tumoral. Para pacientes com CMT esporádico, não foram observadas associações independentes. Nossos resultados evidenciaram relação entre SNPs do gene VEGF-A e fatores prognósticos em CMT sugerindo que essas variantes podem impactar o comportamento tumoral e a apresentação da doença. Em conjunto, nossos resultados indicam que o conhecimento mais aprofundado de marcadores clinicopatológicos ou moleculares específicos podem melhorar a determinação do prognóstico e comportamento tumoral, auxiliando no diagnóstico e no direcionamento para formas de tratamentos mais adequadas.Thyroid nodules are common clinical findings. Thyroid cancer, in contrast, is rare and consists of the most frequent malignant endocrine neoplasia. One of the main challenges in the management of patients with thyroid neoplasms is to identify in addition to clinical parameters, morphological characteristics and molecular changes that are able to differentiate certain tumors that will behave more aggressively than others. The finding of accurate prognostic markers that determine the severity of the case at diagnosis may avoid low-risk patients from being exposed to unnecessary aggressive medical conduct and distinguish these patients from those who, due to their less favorable evolution, require more extensive surgery and follow-up more intense. With advances in the knowledge of the pathogenesis of thyroid neoplasms, numerous studies have been investigating predictive and prognostic markers in relation to thyroid tumors, enabling the development of new antineoplastic agents. Thus, the current trend is that the treatment should be more individualized, considering the clinical condition and morphological, immunohistochemical and molecular markers of the patient and the tumor. The first part of this research work comprises a prospective evaluation in a sample of 615 patients submitted to fine-needle aspiration biopsy (FNAB) guided by ultrasound, the usefulness of thyroid-stimulating hormone (TSH) levels as a predictor of malignancy in thyroid nodules. TSH is a major thyroid cell growth factor, while TSH signaling pathway activation may berequired for the expression of other growth factors, receptors, and proto-oncogenes. Accordingly, TSH suppression is an important therapeutic tool of clinical thyroid cancer management. Interestingly, we observed that higher serum TSH levels were associated with an increased risk of malignancy since patients with malignant nodules presented higher TSH levels than patients with benign nodules in two TSH assays (2.25 vs. 1.50; P = 0.04 and 2.33 vs. 1.27; P = 0.03) and the risk of malignancy was approximately 3-fold higher in patients with TSH levels ≥ 2.26 μU/mL than in patients with lower TSH levels. Our results corroborate previous studies that suggest the use of TSH as an auxiliary diagnostic tool in the stratification of the risk of malignancy associated with thyroid nodules as well as in the decision of therapeutic conduct. The second part of this work, in turn, evaluated in a cohort of 420 patients with medullary thyroid carcinoma (MTC), the role of single nucleotide polymorphisms (SNPs) of the VEGF-A gene in the pathogenesis of the disease through the correlation of the frequencies with clinical, laboratory and prognostic data. It is known that in several tumors, including MTC, there is an overexpression of VEGF-A and its receptors, which makes it possible to use as molecular targets for therapies with multiquinase inhibitors (MKI) and also as prognostic markers. The VEGF-A SNPs rs699947(C>A), rs833061(TC) were genotyped using TaqMan Genotyping Assays. Haplotypes were inferred using Phase program. Of the 420 MTC patients analyzed, 202 (48%) presented hereditary and 218 (52%) had the sporadic form of disease. The mean age of diagnosis was 40 ± 19.7 years and 61% were female. The minor allele frequencies of VEGF-A SNPs were: rs699947 (37.2%), rs833061 (45.6%), and rs2010963 (34.4%). In hereditary MTC, we observed an independent association of the VEGF-A rs833061 with younger age at diagnosis (TT genotype) and smaller tumor size (CC genotype). Additionally, VEGF-A rs2010963 (GG genotype) was correlated with smaller tumor size.Our results showed a relationship between SNPs of the VEGF-A gene and prognostic factors in MTC, suggesting that these variants may impact tumor behavior and disease presentation. These data suggest that further knowledge of clinicopathological or specific molecular markers that may improve prognostic determination and tumor behavior, may assist in the correct definition of the diagnosis as well as targeting more appropriate forms of treatment