Hospital São Rafael

Introduction: Forkhead box E1 (FOXE1) is a transcription factor with a crucial role in thyroid morphogenesis and differentiation. Promoter hypermethylation downregulates FOXE1 expression in different tumor types; nevertheless, its expression and relationship with methylation status in differentiated thyroid cancer (DTC) remain unclear.Methods: A total of 33 pairs of matched samples of PTC tumors and non-tumors were included. Tumor cell cultures were treated with either 5-Aza-2′-deoxycytidine demethylating agent or dimethyl sulfoxide (DMSO). A real-time polymerase chain reaction (RT-PCR) and Western blotting were performed to assess FOXE1 expression. The methylation status was quantified using bisulfite sequencing. A luciferase gene assay was used to determine CpG-island functionality. Gene expression and promoter methylation of FOXE1 and FOXE1-regulated genes were also analyzed with data from The Cancer Genome Atlas (TCGA) thyroid samples.Results: After demethylating treatment, increased FOXE1 mRNA was observed concomitantly with reduced promoter methylation of CpGisland2. A negative correlation between mRNA downregulation and an increased methylation level of CpGisland2 was observed in tumors. Diminished protein expression was also detected in some DTC cell lines and in some tumor samples, suggesting the involvement of post-transcriptional regulatory mechanisms. CPGisland2 was proved to be an enhancer. TCGA data analysis showed low FOXE1 mRNA expression in tumors with a negative correlation with methylation status and a positive correlation with the expression of most of its target genes. Reduced FOXE1 expression, accompanied by a high methylation level, was associated with PTC aggressiveness (tall cell variant, advanced extra thyroid extension, T4 American Joint Committee on Cancer (AJCC) classification), age at diagnosis (over 45 years old), and presence of a BRAFV600E mutation.Conclusion: FOXE1 mRNA was downregulated in DTC compared with non-tumors, followed by high CpGisland methylation. A coupling of low mRNA expression and high methylation status was related to characteristics of aggressiveness in DTC tumors.

Erika Urbano De Lima; Filipe Ferreira Dos Santos; Igor Campos Da Silva; Cláudio Rogério Alves De Lima; Vitoria Sousa Frutuoso; Gustavo Felisola Caso; Paloma Ramos De Oliveira; Ana Karina Bezerra; Janete Maria Cerutti; Rodrigo Esaki Tamura; Helton Estrela Ramos; Ileana Gabriela Sanchez de Rubio; Cl. Reduced expression of FOXE1 in differentiated thyroid cancer, the contribution of CPG methylation, and their clinical relevance. Frontiers in Endocrinology 2024, 15, 1454349 .

Erika Urbano De Lima, Filipe Ferreira Dos Santos, Igor Campos Da Silva, Cláudio Rogério Alves De Lima, Vitoria Sousa Frutuoso, Gustavo Felisola Caso, Paloma Ramos De Oliveira, Ana Karina Bezerra, Janete Maria Cerutti, Rodrigo Esaki Tamura, Helton Estrela Ramos, Ileana Gabriela Sanchez de Rubio, Cl. Reduced expression of FOXE1 in differentiated thyroid cancer, the contribution of CPG methylation, and their clinical relevance. Frontiers in Endocrinology. 2024; 15 ():1454349.

Erika Urbano De Lima; Filipe Ferreira Dos Santos; Igor Campos Da Silva; Cláudio Rogério Alves De Lima; Vitoria Sousa Frutuoso; Gustavo Felisola Caso; Paloma Ramos De Oliveira; Ana Karina Bezerra; Janete Maria Cerutti; Rodrigo Esaki Tamura; Helton Estrela Ramos; Ileana Gabriela Sanchez de Rubio; Cl. 2024. "Reduced expression of FOXE1 in differentiated thyroid cancer, the contribution of CPG methylation, and their clinical relevance." Frontiers in Endocrinology 15, no. : 1454349.

Introduction: Septic shock, a life-threatening condition, can result in cerebral dysfunction and heightened mortality rates. In these patients, disturbances in cerebral hemodynamics, as reflected by impairment of myogenic cerebral autoregulation (CA), metabolic regulation, expressed by critical closing pressure (CrCP) and reductions in intracranial compliance (ICC), can adversely impact septic shock outcomes. The general recommendation is to maintain a target mean arterial pressure (MAP) of 65 mmHg but the effect of different MAP targets on cerebral hemodynamics in these patients is not clear and optimal targets might be dependent on the status of CA. This protocol aims to assess the cerebral hemodynamics profile at different pressure targets in septic shock patients. Methods: Prospective, non-randomized, single-center trial, which will study cerebral hemodynamics in patients with septic shock within 48 hours of its onset. Patients will be studied at their baseline MAP and at three MAP targets (T1: 65, T2: 75, T3: 85 mmHg). Cerebral hemodynamics will be assessed by transcranial Doppler (TCD) and a skull micro-deformation sensor (B4C). Dynamic CA will be expressed by the autoregulation index (ARI), calculated by transfer function analysis, using fluctuations of MAP as input and corresponding oscillations in cerebral blood velocity (CBv). The instantaneous relationship between arterial blood pressure and CBv will be used to estimate CrCP and resistance-area product (RAP) for each cardiac cycle using the first harmonic method. The B4C will access ICC by intracranial pressure waveforms (P2/P1). The primary aim is to assess cerebral hemodynamics (ARI, CrCP, RAP, and P2/P1) at different targets of MAP in septic shock patients. Our secondary objective is to assess cerebral hemodynamics at 65mmHg (target recommended by guidelines). In addition, we will assess the correlation between markers of organ dysfunction (such as lactate levels, vasoactive drugs usage, SOFA score, and delirium) and CA. Ethics and dissemination: The results of this study may help to understand the effect of the recommended MAP and variations in blood pressure in patients with septic shock and impaired CA and ICC. Furthermore, the results can assist large trials in establishing new hypotheses about neurological management in this group of patients. Approval was obtained from the local Ethics Committee (28134720.1.0000.0048). It is anticipated that the results of this study will be presented at national and international conferences and will be published in peer-reviewed journals in 2024 and 2025. Trial registration: Trial registration number: NCT05833607. https://clinicaltrials.gov/study/NCT05833607.

Pedro Cury; Rogério da Hora Passos; Fernanda Alves; Sérgio Brasil; Gustavo Frigieri; Fabio S. Taccone; Ronney B. Panerai; Juliana Caldas. Impact of different blood pressure targets on cerebral hemodynamics in septic shock: A prospective pilot study protocol—SEPSIS-BRAIN. PLOS ONE 2024, 19, e0304412 .

Pedro Cury, Rogério da Hora Passos, Fernanda Alves, Sérgio Brasil, Gustavo Frigieri, Fabio S. Taccone, Ronney B. Panerai, Juliana Caldas. Impact of different blood pressure targets on cerebral hemodynamics in septic shock: A prospective pilot study protocol—SEPSIS-BRAIN. PLOS ONE. 2024; 19 (10):e0304412.

Pedro Cury; Rogério da Hora Passos; Fernanda Alves; Sérgio Brasil; Gustavo Frigieri; Fabio S. Taccone; Ronney B. Panerai; Juliana Caldas. 2024. "Impact of different blood pressure targets on cerebral hemodynamics in septic shock: A prospective pilot study protocol—SEPSIS-BRAIN." PLOS ONE 19, no. 10: e0304412.

Background: Hypotension during dialysis arises from vasomotor tone alterations and hypovolemia, with disrupted counterregulatory mechanisms in acute kidney injury (AKI) patients. This study investigated the predictive value of preload dependency, assessed by the passive leg raising (PLR) test, and arterial tone, measured by dynamic elastance (Eadyn), for intradialytic hypotension (IDH). Methods: In this prospective observational study conducted in a tertiary hospital ICU, hemodynamic parameters were collected from critically ill AKI patients undergoing intermittent hemodialysis using the FloTrac/Vigileo system. Baseline measurements were recorded before KRT initiation, including the PLR test and Eadyn calculation. IDH was defined as mean arterial pressure (MAP) < 65 mmHg during dialysis. Logistic regression was used to identify predictors of IDH, and Kaplan–Meier analysis assessed 90-day survival. Results: Of 187 patients, 27.3% experienced IDH. Preload dependency, identified by positive PLR test, was significantly associated with IDH (OR 8.54, 95% CI 5.25–27.74), while baseline Eadyn was not predictive of IDH in this cohort. Other significant predictors of IDH included norepinephrine use (OR 16.35, 95% CI 3.87–68.98) and lower baseline MAP (OR 0.96, 95% CI 0.94–1.00). IDH and a positive PLR test were associated with lower 90-day survival (p < 0.001). Conclusions: The PLR test is a valuable tool for predicting IDH in critically ill AKI patients undergoing KRT, while baseline Eadyn did not demonstrate predictive value in this setting. Continuous hemodynamic monitoring, including assessment of preload dependency, may optimize patient management and potentially improve outcomes. Further research is warranted to validate these findings and develop targeted interventions to prevent IDH.

Rogério da Hora Passos; Fernanda Oliveira Coelho; Juliana Ribeiro Caldas; Erica Batista Dosde Santos Galvãomelo; Augusto Manoel de Carvalho Farias; Octávio Henrique Coelho Messeder; Etienne Macedo. Predicting intradialytic hypotension in critically ill patients undergoing intermittent hemodialysis: a prospective observational study. Intensive Care Medicine Experimental 2024, 12, 1 -9.

Rogério da Hora Passos, Fernanda Oliveira Coelho, Juliana Ribeiro Caldas, Erica Batista Dosde Santos Galvãomelo, Augusto Manoel de Carvalho Farias, Octávio Henrique Coelho Messeder, Etienne Macedo. Predicting intradialytic hypotension in critically ill patients undergoing intermittent hemodialysis: a prospective observational study. Intensive Care Medicine Experimental. 2024; 12 (1):1-9.

Rogério da Hora Passos; Fernanda Oliveira Coelho; Juliana Ribeiro Caldas; Erica Batista Dosde Santos Galvãomelo; Augusto Manoel de Carvalho Farias; Octávio Henrique Coelho Messeder; Etienne Macedo. 2024. "Predicting intradialytic hypotension in critically ill patients undergoing intermittent hemodialysis: a prospective observational study." Intensive Care Medicine Experimental 12, no. 1: 1-9.