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Análise da expressão de genes envolvidos na síntese de translesão e na integridade do DNA em pacientes com leucemia mieloide crônica em uso de inibidores de tirosina-quinase

2026-06-17T20:43:06Z

Título: Análise da expressão de genes envolvidos na síntese de translesão e na integridade do DNA em pacientes com leucemia mieloide crônica em uso de inibidores de tirosina-quinase Autor(es): Gadelha, Anna Thawanny Gadelha Abstract: Introduction: Chronic Myeloid Leukemia (CML) is a hematologic neoplasm characterized by the presence of the Philadelphia chromosome (Ph), resulting from the t(9;22)(q34;q11) translocation, which generates the BCR-ABL fusion gene. This gene encodes an oncoprotein with constitutive tyrosine kinase activity that drives CML pathogenesis by promoting DNA damage and compromising genomic integrity. Tyrosine kinase inhibitors (TKIs), such as imatinib, dasatinib, and nilotinib, are fundamental in the treatment of CML; however, concerns remain regarding their genotoxic effects and the role of DNA damage repair and damage tolerance mechanisms under therapeutic pressure. Objective: This study aimed to investigate the expression of genes involved in translesion synthesis and maintenance of genomic integrity (REV1, SETD2, APEX1, and POLB) in patients with CML receiving first- or second-generation TKIs, and to explore their implications for genomic stability and treatment response. Methods: A cross-sectional study was conducted involving 71 patients with chronic-phase CML and 25 healthy individuals as the control group. Clinical and laboratory data were collected from medical records. Peripheral blood samples were obtained, and gene expression was quantified by RT-qPCR. Differences in gene expression between groups and prognostic variables were evaluated using Mann-Whitney and Kruskal-Wallis tests with Dunn/Bonferroni post hoc analysis. Multivariate logistic regression (stepwise method) and ROC curve analyses were employed to assess the predictive value of genes for the absence of complete cytogenetic response (CCyR) and molecular response (MR). Additionally, a MANOVA was performed, adjusted for therapeutic response (CCyR, MR) and type of TKI, to identify joint effects on gene expression. Results: In the initial comparison, a significant reduction in POLB and APEX1 expression was observed in CML patients compared to controls (p < 0.0001), indicating impairment of the base excision repair (BER) pathway. Patients with an altered karyotype showed higher expression of APEX1 (p < 0.0001), and those classified as low-risk according to the EUTOS score exhibited higher POLB levels (p = 0.049). Stratification by type of TKI demonstrated that dasatinib or nilotinib use was associated with increased expression of REV1 and SETD2 (p < 0.005) compared to imatinib. MANOVA indicated a statistically significant effect on REV1 (p = 0.001) and SETD2 (p = 0.045) expression, reflecting the influence of treatment type and clinical response. In ROC curve analyses, REV1 showed an AUC of 0.733 for absence of CCyR (95% CI: 0.564–0.909) and 0.721 for absence of MR (95% CI: 0.564–0.877). In multivariate logistic regression, REV1 overexpression increased the odds of absence of CCyR by approximately 16-fold (OR = 15.9; p = 0.039), while high SETD2 expression exerted a protective effect (OR = 0.358; p = 0.022). Additionally, low APEX1 expression was more pronounced in patients refractory to achieving CCyR, underscoring the essential role of BER in maintaining genomic stability. Conclusion: The results indicate that deficiency of POLB and APEX1, combined with activation of REV1 and SETD2, is strongly associated with genomic instability and therapeutic resistance in CML. The use of second-generation TKIs further reinforced the reliance on damage tolerance mechanisms, highlighting the importance of the REV1-mediated TLS pathway. REV1 overexpression emerged as an independent predictor of poor prognosis, whereas SETD2 exerted a protective effect, suggesting their potential as molecular biomarkers for risk stratification and optimization of therapeutic strategies. In this context, an integrated understanding of DNA repair and damage tolerance pathways provides critical insights for preventing clonal evolution and improving the clinical management of CML patients. Tipo: Tese

O que você sabe sobre o uso de métodos não farmacológicos para alívio da dor no parto? Vamos conhecer!

2026-06-17T17:14:08Z

Título: O que você sabe sobre o uso de métodos não farmacológicos para alívio da dor no parto? Vamos conhecer! Autor(es): Balsells, Marianne Maia Dutra; Aquino, Priscila de Souza Tipo: Folheto

Reações adversas a medicamento sem pacientes hospitalizados por insuficiência hepática crônica moderada ou grave em hospitais do Nordeste do Brasil

2026-06-11T17:18:22Z

Título: Reações adversas a medicamento sem pacientes hospitalizados por insuficiência hepática crônica moderada ou grave em hospitais do Nordeste do Brasil Autor(es): Araújo, Breno Queiroz de Abstract: Chronic liver failure (CLF) is characterized by progressive and irreversible loss of liver function, which may lead to alterations in the pharmacokinetics of various medications and increased susceptibility to adverse drug reactions (ADRs). In this context, the clinical pharmacist plays a fundamental role in the prevention, identification, and management of these reactions. This study aimed to characterize the incidence, determinants, and clinical relevance of ADRs in patients hospitalized with moderate to severe CLF in hospitals in the Northeast region of Brazil. This is an observational, analytical, multicenter prospective cohort study that included patients with moderate to severe CLF (Child-Pugh B or C) hospitalized in seven hospitals in Northeast Brazil between September 2023 and January 2026. Daily collection of clinical, laboratory, and pharmacotherapeutic data was performed, with active surveillance of ADRs through medical record review, trigger tools, and reports from the healthcare team and patients. ADRs were coded according to the Medical Dictionary for Regulatory Activities (MedDRA®) and classified regarding causality, severity, and preventability using validated tools. Data analysis was performed using Stata 15®, adopting a significance level of p < 0.05. A total of 252 patients were included, with a predominance of males (59.1%) and a mean age of 59.2 years. Overall, 38.9% of patients experienced at least one ADR, totaling 207 events. The most frequent ADRs involved gastrointestinal, nervous system, and metabolic disorders, with furosemide, lactulose, and carvedilol identified as the main suspected drugs. Most ADRs were classified as probable or possible, of mild severity, and largely preventable. ADRs were associated with longer follow-up time, previous upper gastrointestinal bleeding, and laboratory abnormalities suggestive of hepatic and renal dysfunction, such as elevated urea, bilirubin, and aspartate aminotransferase (AST), as well as hyponatremia. ADRs were also associated with relevant clinical outcomes, including hepatorenal syndrome, prophylactic variceal ligation, acute-on-chronic liver failure, jaundice, and hepatic coma. In conclusion, ADRs are frequent in patients with CLF, many of which are preventable, and are associated with worse clinical outcomes, highlighting the need for rigorous pharmacotherapeutic monitoring and strategies to ensure safe medication use in this population. Tipo: Dissertação

Protocolo assistencial de enfermagem para prevenção dos cânceres de mama e colo de útero em pessoas transmasculinas: estudo metodológico

2026-06-11T11:54:31Z

Título: Protocolo assistencial de enfermagem para prevenção dos cânceres de mama e colo de útero em pessoas transmasculinas: estudo metodológico Autor(es): Silva, Denise Montenegro da Abstract: The present study aimed to develop a nursing care protocol for the prevention of breast and cervical cancers among transmasculine individuals. This methodological study was conducted from June 2024 to January 2026, following the Iowa Model of Evidence-Based Practice to Promote Excellence in Health through eight stages: identifying a research question; securing organizational support by recognizing the topic as a priority; conducting a scoping review; designing and implementing a pilot for practice change, involving the team while considering preferences, resources, constraints, and approval processes; developing a protocol and implementation plan, collecting data, and evaluating processes; assessing whether the practice change was appropriate and ready for implementation; integrating the change directly into the current system while monitoring key indicators; and, finally, disseminating the results. The validation stage was conducted using a hybrid format (face-to-face and online). Content validation was performed by seven specialist nurses (online), five individuals from the target care population (hybrid format with members of the Associação Transmasculina do Ceará), and five primary healthcare nurses who evaluated the usability of the protocol (online). Only the penultimate stage was not fully completed. Data were analyzed and presented using descriptive statistics, including absolute and relative frequencies. In addition, item-level content validity indices and the specific calculation required by the evaluation tool were computed. Ethical principles were observed throughout all stages of the study, ensuring participant anonymity. The study results included: the production of a scoping review published in a highly relevant international journal; systematic meetings with the transmasculine population to understand perceptions and preferences regarding the topic; organization, analysis, and interpretation of the data culminating in the development of the protocol; and content validation, in which the overall protocol evaluation by specialists was 0.85, indicating good overall quality, with Domain 5 (Applicability) showing the lowest level of agreement (0.71). Among the transmasculine population, the overall evaluation was 0.95, with Domain 6 (Editorial Independence) presenting the lowest level of agreement (0.55). Following the validation stage, evaluators’ considerations were analyzed, and the relevant modifications were incorporated into the instrument. Regarding usability, the protocol was recognized as a practical and easily implementable tool. In conclusion, the protocol demonstrated valid content and usability within the context of primary healthcare, enabling nurses to guide preventive care practices through evidence-based actions delivered in a more inclusive manner to transmasculine populations. Tipo: Tese