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Introdução: Neoplasias mieloproliferativas BCR::ABL1 negativas são doenças clonais das células-tronco hematopoiéticas, caracterizadas por panmielose, com maturação eficaz. Trombocitemia essencial (TE) e policitemia vera (PV) são as mais frequentes, diferenciadas por parâmetros laboratoriais, clínicos e achados genéticos. JAK2V617F é responsável por 95% dos casos de PV e de 50-60% de TE, ao passo que variantes genéticas em MPL e CARL são encontradas em 3% e 30% dos casos de TE, respectivamente. A predisposição hereditária para neoplasias mieloproliferativas é rara e caracteriza-se por baixa penetrância, a presença de variantes genéticas somáticas e um risco aumentado de progressão para leucemia mieloide aguda. A condição pode ocorrer em dois ou mais membros da mesma família, tornando os casos familiares particularmente notáveis. Este estudo descreve um caso raro de neoplasias mieloproliferativas familiares identificadas entre pacientes atendidos na Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas. Métodos: Análise dos prontuários médicos de pacientes que consentiram em participar da pesquisa entre 2021 e 2022. Foram avaliados dados clínicos, laboratoriais, eventos hemorrágicos e trombóticos. Análise molecular foi realizada para identificação de JAK2V617F, haplótipo 46/1 (rs10974944 C>G), MPL (éxon 10) e CALR (éxon 9). Resultados: foram identificados casos de neoplasia mieloproliferativa em dois membros do mesmo grupo familiar: NMP102, mulher, 86 anos diagnosticada com trombocitemia essencial, sem histórico de esplenomegalia ou eventos trombóticos, mas teve eventos hemorrágicos e história de tratamento com hidroxiureia. Exames citogenéticos revelaram uma deleção 3q; foi identificada uma variante tipo 2 no gene CALR (rs765476509 - c.1154_1155insTTGTC; p.K385fs*47). Seu filho, NMP35, de 60 anos, apresenta diagnostico para policitemia vera, histórico de esplenomegalia, sem eventos trombóticos ou hemorrágicos relatados, tratado com hidroxiuréia e ácido acetilsalicílico. Foi identificada a variante JAK2V617F em homozigose (T/T). Ambos apresentaram o haplótipo 46/1 (C/G e G/G, respectivamente). Discussão: O presente estudo relata pela primeira vez um caso de diferentes tipos de neoplasias mieloproliferativas em um único grupamento familiar no Amazonas. A identificação de diferentes tipos de variantes drivers dos casos está de acordo com os achados genéticos drivers envolvidos na etiopatogênese das doenças, assim como o haplótipo 46/1 é enriquecido em casos familiares, elevando o risco de 5 a 7 vezes de desenvolvimento dessas doenças em parentes de primeiro grau. Variantes somáticas (como JAK2V617F e c.1154_1155insTTGTC) contribuem para a vantagem proliferativa e a subsequente clonalidade celular, enquanto o componente hereditário (haplótipo 46/1 - rs10974944 C>G), predispõe à aquisição dessas alterações somáticas, estabelecendo o distúrbio mieloproliferativo clonal. Conclusão: É relevante analisar as variantes associadas ao haplótipo germinativo 46/1 em contextos familiares para entender seu papel na hereditariedade e sua possível conexão com a neoplasia mieloproliferativa familiar.

A trombocitemia essencial é uma neoplasia mieloproliferativa onde ocorre a proliferação exacerbada de megacariócitos e trombocitose no sangue periférico. A hidroxiureia é um citorredutor indicado como tratamento de primeira linha para essa patologia. As microvesículas (MVs) são liberadas por diversos tipos de células e atuam no transporte de cargas capazes de alterar o fenótipo e comportamento das células, na sinalização intercelular, na evasão imune e na modulação do microambiente, favorecendo processos inflamatórios e trombóticos. Objetivo: Neste estudo investigamos caracterizar o perfil das microvesículas circulantes provenientes de linfócitos em pacientes com diagnóstico de trombocitemia essencial que estão fazendo uso de hidroxiureia. Materiais e métodos: Foram incluídos 76 indivíduos no grupo de estudo, sendo 38 pacientes com diagnostico confirmado de trombocitemia essencial e 38 indivíduos para o grupo controle. As análises das amostras foram realizadas por citometria de fluxo. Resultados: O grupo com TE apresentou o maior número de MVs totais e dos marcadores: CD3, CD19 e CD56 quando comparados com os indivíduos controles. Os pacientes com a variante genética JAK2V617F+ possuíam uma população menor de MVs CD3 do que os pacientes sem essa variante. Também foi possível observar uma diminuição de MVs CD19 com o aumento do tempo de tratamento. Discussão: A presença de populações de MVs derivadas de células do sistema imune, podem ser explicadas pela atuação dessas células na fisiopatologia da TE ao liberar citocinas que promovem o estado inflamatório dos pacientes. A diminuição das MVs CD3 em pacientes JAK2V617F+ pode estar associada a modulação da resposta imunológica. Estudos anteriores observaram que pacientes diagnosticados com TE tratados com Hidroxiureia demostram uma melhora continua com o tratamento, tanto clinicamente com a diminuição da incidência de eventos trombóticos, como também a diminuição significativa da carga alélica da variante JAK2V617F, dessa forma o tratamento a longo prazo com a hidroxiureia leva a diminuição de diversos processos patológicos da doença. Conclusão: Nosso estudo comprovou que diversas populações de MVs podem estar envolvidas na patogênese da TE e que mesmo após o tratamento o nível de MVs circulantes provenientes de linfócitos continua elevado. Essas populações de MVs contribuem de forma direta ou indireta para a progressão dessa neoplasia, como por exemplo, favorecendo a coagulação e/ou inflamação e modulando a resposta imunológica. Também foi possível encontrar uma associação entre a diminuição do número total de MVs com o aumento do tempo de tratamento.

BCR::ABL1-negative myeloproliferative neoplasms are hematopoietic disorders characterized by panmyelosis. JAK2 V617F is a frequent variant in these diseases and often occurs in the 46/1 haplotype. The G allele of rs10974944 has been shown to be associated with this variant, specifically its acquisition, correlations with familial cases, and laboratory alterations. This study evaluated the association between the 46/1 haplotype and JAK2 V617F in patients with myeloproliferative neoplasms in a population from the Brazilian Amazon. Clinical, laboratory and molecular sequencing analyses were considered. Carriers of the G allele of rs10974944 with polycythemia vera showed an increase in mean corpuscular volume and mean corpuscular hemoglobin, while in those with essential thrombocythemia, there was an elevation in red blood cells, hematocrit, and hemoglobin. Associations were observed between rs10974944 and the JAK2 V617F, in which the G allele (OR 3.4; p < 0.0001) and GG genotype (OR 4.9; p = 0.0016) were associated with JAK2 V617F + and an increase in variant allele frequency (GG: OR 15.8; p =  < 0.0001; G: OR 6.0; p = 0.0002). These results suggest an association between rs10974944 (G) and a status for JAK2 V617F, JAK2 V617F + &#95;VAF ≥ 50%, and laboratory alterations in the erythroid lineage., (© 2024. The Author(s).)

JAK2V617F (dbSNP: rs77375493 ) is the most frequent and most-studied variant in BCR::ABL1 negative myeloproliferative neoplasms and in the JAK2 gene. The present study aimed to molecularly characterize variants in the complete coding region of the JAK2 gene in patients with BCR::ABL1 negative chronic myeloproliferative neoplasms. The study included 97 patients with BCR::ABL1 negative myeloproliferative neoplasms, including polycythemia vera (n=38), essential thrombocythemia (n=55), and myelofibrosis (n=04). Molecular evaluation was performed using conventional PCR and Sanger sequencing to detect variants in the complete coding region of the JAK2 gene. The presence of missense variants in the JAK2 gene including rs907414891, rs2230723, rs77375493 (JAK2V617F) , and rs41316003 were identified. The coexistence of variants was detected in polycythemia vera and essential thrombocythemia. Thus, individuals with high JAK2V617F variant allele frequency (≥50% VAF) presented more thrombo-hemorrhagic events and manifestations of splenomegaly compared with those with low JAK2V617F variant allele frequency (<50% VAF). In conclusion, individuals with BCR::ABL1 negative neoplasms can display >1 variant in the JAK2 gene, especially rs2230722 , rs2230724 , and rs77375493 variants, and those with high JAK2V617F VAF show alterations in the clinical-laboratory profile compared with those with low JAK2V617F VAF., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Torres et al.)

Introduction: Menthol, through its cooling and pleasant sensory effects, facilitates smoking and tobacco product initiation, resulting in the high popularity of mint/menthol-flavored E-cigarettes. More recently, E-cigarette vendors started marketing synthetic cooling agents as additives that impart a cooling effect but lack a characteristic minty odor. Knowledge about content of synthetic coolants in US-marketed E-cigarette products and associated health risks is limited., Aims and Methods: E-liquid vendor sites were searched with the terms "koolada", "kool/cool", "ice", or WS-3/WS-23, denoting individual cooling agents, and relevant refill E-liquids were purchased. "Ice" flavor varieties of Puffbar, the most popular disposable E-cigarette brand, were compared with non-"Ice" varieties. E-liquids were characterized, and synthetic coolants quantified using GC/MS. Margin of exposure (MOE), a risk assessment parameter, was calculated to assess the risk associated with synthetic coolant exposure from E-cigarette use., Results: WS-3 was detected in 24/25 refill E-liquids analyzed. All Puffbar flavor varieties contained either WS-23 (13/14) or WS-3 (5/14), in both "Ice"- and non-"Ice" flavors. Modeling consumption of WS-3 from vaped E-liquids, resulted in MOEs below the safe margin of 100 for most daily use scenarios. MOEs for WS-23 were <100 for 10/13 Puffbar flavors in all use scenarios. Puffbar power specifications are identical to Juul devices., Conclusions: Synthetic cooling agents (WS-3/WS-23) were present in US-marketed E-cigarettes, at levels that may result in consumer exposures exceeding safety thresholds set by regulatory agencies. Synthetic coolants are not only found in mint- or menthol-flavored products but also in fruit- and candy-flavored products, including popular disposable E-cigarette products such as Puffbar., Implications: Synthetic cooling agents are widely used in "kool/cool"- and "ice"-flavored E-liquids and in E-liquids without these labels, both as a potential replacement for menthol or to add cooling "notes" to nonmenthol flavors. These agents may be used to bypass current and future regulatory limits on menthol content in tobacco products, and not just E-cigarettes. Because synthetic cooling agents are odorless, they may not fall under the category of "characterizing flavor", potentially circumventing regulatory measures based on this concept. Regulators need to consider the additional health risks associated with exposure to synthetic cooling agents., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The JAK2 V617F variant constitutes a genetic alteration of higher frequency in BCR/ABL1 negative chronic myeloproliferative neoplasms, which is caused by a substitution of a G ˃ T at position 1849 and results in the substitution of valine with phenylalanine at codon 617 of the polypeptide chain. Clinical, morphological and molecular genetic features define the diagnosis criteria of polycythemia vera, essential thrombocythemia and primary myelofibrosis. Currently, JAK2 V617F is associated with clonal hematopoiesis, genomic instability, dysregulations in hemostasis and immune response. JAK2 V617F clones induce an inflammatory immune response and lead to a process of immunothrombosis. Recent research has shown great interest in trying to understand the mechanisms associated with JAK2 V617F signaling and activation of cellular and molecular responses that progressively contribute to the development of inflammatory and vascular conditions in association with chronic myeloproliferative neoplasms. Thus, the aim of this review is to describe the main genetic, hematological and immunological findings that are linked to JAK2 variant signaling in chronic myeloproliferative neoplasms.

Objective: To discuss how care-permanence comprehensiveness is for patients undergoing treatment in nephrology., Method: A qualitative, exploratory and descriptive study anchored in Sociopoetics, conducted in the first semester of 2018, in Rio de Janeiro, Brazil, with nurses from nephrology services. The data were produced after applying the creative technique with drawings and collages and taking recorded statements about the signifieds and signfiers of care-permanence. The analysis was performed based on the principles of Sociopoetics from the philosophical conceptions of the research groups., Results: Fifteen (15) nurses with experience in nephrology services participated in this study. Four conceptual axes were shared referring to: comprehensive care; complex care; continuous care; and inclusive care, which considers the patient's family, team, society and their context, in addition to the patient themselves., Conclusion: A philosophical reflection on care of the human being implies considering the physical, emotional, and individual dimensions, but also its micro and macromolecular revolutions of existence as a social being. The nature of knowledge from the ludic production enabled reflection and awareness for all the time and at all times about the comprehensiveness of care by nurses in nephrology.

Purpose: To determine the prevalence of uterine leiomyomas, diagnosed by ultrasound, in a private health care setting located in the central eastern region of Portugal, and to explore the demographic and clinical factors related to diagnosis and symptomatology., Patients and Methods: The files of 624 patients attending a private clinic in Covilhã, Portugal, from January 2 to December 31, 2010 were retrieved for evaluation. Pelvic ultrasound record, age, weight, height, age at menarche, number of pregnancies and deliveries, marital status, menstrual cycles characteristic, and contraceptive method at consultation were included in the analysis., Results: Uterine leiomyoma (UL) was diagnosed by ultrasonography in 161 (25.8%) patients. A single UL was diagnosed in 80 (49.7%) patients. In 79 (49.1%) patients, the largest leiomyoma had a dimension <20 mm. Prevalence of UL was age dependent: at 11.0% for women 20-39 years old; 45.4% for those aged 40-59 years; and 19.5% for women 60 years or older. Metrorrhagia was the most distressing presenting symptom. When menorrhagia was the presenting symptom, the probability of having an ultrasound diagnosis of UL was 73.3%. Metrorrhagia or menorrhagia, as presenting symptom, was significantly related to the ultrasound diagnosis of multiple ULs., Conclusion: UL was especially prevalent in women aged between 40 and 59 years. Patients with multiple ULs had significantly more abnormal uterine bleeding. In patients with menorrhagia or metrorrhagia, special attention should be taken in searching for the presence of multiple ULs during ultrasound.