The Brazilian national prospective active surveillance (AS) cohort of patients with low-risk prostate cancer in the public health system: vigiaSUS study protocol.

BACKGROUND: Prostate cancer exhibits a very diverse behaviour, with some patients dying from the disease and others never needing treatment. Active surveillance (AS) consists of periodic PSA assessment (prostate-specific antigen), DRE (digital rectal examination) and periodic prostate biopsies. According to the main guidelines, AS is the preferred strategy for low-risk patients, to avoid or delay definitive treatment. However, concerns remain regarding its applicability in certain patient subgroups, such as African American men, who were underrepresented in the main cohorts. Brazil has a very racially diverse population, with 56.1% self-reporting as brown or black. The aim of this study is to evaluate and validate the AS strategy in low-risk prostate cancer patients following an AS protocol in the Brazilian public health system. METHODS: This is a multicentre AS prospective cohort study that will include 200 patients from all regions of Brazil in the public health system. Patients with prostate adenocarcinoma and low-risk criteria, defined as clinical staging T1-T2a, Gleason score ≤ 6, and PSA < 10 ng/ml, will be enrolled. Archival prostate cancer tissue will be centrally reviewed. Patients enrolled in the study will follow the AS strategy, which involves PSA and physical examination every 6 months as well as multiparametric MRI (mpMRI) every two years and prostate biopsy at month 12 and then every two years. The primary objective is to evaluate the reclassification rate at 12 months, and secondary objectives include determining the treatment-free survival rate, metastasis-free survival, and specific and overall survival. Exploratory objectives include the evaluation of quality of life and anxiety, the impact of PTEN loss and the economic impact of AS on the Brazilian public health system. DISCUSSION: This is the first Brazilian prospective study of patients with low-risk prostate cancer under AS. To our knowledge, this is one of the largest AS study cohort with a majority of nonwhite patients. We believe that this study is an opportunity to better understand the outcomes of AS in populations underrepresented in studies. Based on these data, an AS national clinical guideline will be developed, which may have a beneficial impact on the quality of life of patients and on public health. TRIAL REGISTRATION: Clinicaltrials registration is NCT05343936.

Evaluation of UGT1A1 and CYP3A Genotyping and Single-Point Irinotecan and Metabolite Concentrations as Predictors of the Occurrence of Adverse Events in Cancer Treatment.

PURPOSE: The variability on irinotecan (IRI) pharmacokinetics and toxicity has been attributed mostly to genetic variations in the UGT1A1 gene, responsible for conjugation of the active metabolite SN-38. Also, CYP3A mediates the formation of inactive oxidative metabolites of IRI. The association between the occurrence of severe adverse events, pharmacokinetics parameters, and UGT1A1 and CYP3A4 predicted phenotypes was evaluated, as the evaluation of [SN-38]/IRI dose ratio as predictor of severe adverse events. METHODS: Forty-one patients undergoing IRI therapy were enrolled in the study. Blood samples were collected 15 min after the end of drug the infusion, for IRI, SN-38, SN-38G, bilirubin concentrations measurements, and UGT1A1 and CYP3A genotype estimation. Data on adverse event was reported. RESULTS: Fifteen patients (36.5%) developed grade 3/4 adverse events. A total of 9.8% (n = 4) of the patients had UGT1A1 reduced activity phenotype, and 48.7% (n = 20) had UGT1A1 and 63.4% (n = 26) CYP3A intermediary phenotypes. Severe neutropenia and diarrhea were more prevalent in patients with reduced UGT1A1 in comparison with functional metabolism (50% and 75% versus 0% and 13%, respectively). SN-38 levels and its concentrations adjusted by IRI dose were significantly correlated to toxicity (rs = 0.31 (p = 0.05) and rs = 0.425 (p < 0.01)). The [SN-38]/IRI dose ratio had a ROC curve of 0.823 (95% CI 0.69-0.956) to detect any severe adverse event and 0.833 (95% CI 0.694-0.973) to detect severe diarrhea. The cut-off of 0.075 ng mL-1 mg-1 had 100% sensitivity and 65.7% specificity to predict severe diarrhea. CONCLUSION: Our data confirmed the relevance of the pre-emptive genotypic information of UGT1A1. The [SN-38]/IRI ratio, measured 15 min after the end of the IRI infusion, was a strong predictor of severe toxicity and could be applied to minimize the burden of patients after IRI administration.

Arterite de Takayasu diagnosticada durante o puerpério em mulher com doença hipertensiva gestacional: relato de caso / Takayasu Arteritis diagnosed during puerperium in a woman with pregnancy-induced hypertension: Case report

Objetivos: Descrever um caso de Arterite de Takayasu diagnosticada durante o puerpério precoce, demonstrando a importância da aferição adequada da pressão arterial para o diagnóstico da doença hipertensiva gestacional.Descrição do caso: Uma mulher de 40 anos, em sua quarta gestação, com idade gestacional de 36 semanas e três dias, foi hospitalizada por gestação de alto risco devido a hipertensão arterial sistêmica crônica. Durante a internação observou-se diferença nos níveis tensionais e assimetria de pulsos entre os membros superiores. No pós-parto a paciente foi submetida à ecografia de carótidas com Doppler, que demonstrou oclusão de artéria carótida comum esquerda e de artéria subclávia esquerda, levando ao diagnóstico de Arterite de Takayasu.Conclusões: O diagnóstico precoce da Arterite de Takayasu é difícil, pois as manifestações iniciais são inespecíficas e os sintomas discretos. Entretanto, um exame físico cuidadoso pode evidenciar sinais que suscitem suspeitas e justifiquem investigação adicional, podendo prevenir um desfecho negativo, especialmente no período gestacional.

Aims: To describe a case of Takayasu arteritis diagnosed during the early postpartum period, demonstrating the importance of proper blood pressure measurement for the diagnosis of gestational hypertension.Case description: A 40 year old woman in her fourth pregnancy, with gestational age of 36 weeks and three days, was hospitalized for highrisk pregnancy due to chronic hypertension. During hospitalization, difference in blood pressure levels and pulse asymmetry between the upper limbs were observed. In the postpartum the patient underwent carotid Doppler ultrasound, which showed occlusion of the left common carotid artery and left subclavian artery, leading to the diagnosis of Takayasu arteritis. Conclusions: Early diagnosis of Takayasu arteritis is difficult because initial manifestations are nonspecific and symptoms are mild. However, a careful physical examination may reveal signs that raise suspicion and warrant further investigation, which may prevent a negative outcome, especially during pregnancy.

Tratamento medicamentoso da hipertensão / Pharmacological treatment of hypertension

A hipertensão arterial sistêmica (HAS) afeta cerca de 30% da população adulta mundial. Pode ser definida como a elevação persistente da pressão arterial (PA) acima de 140/90 mmHg. Em cerca de 5-10% dos hipertensos, identifica-se uma causa secundária de HAS. Contudo, a maioria dos pacientes apresenta o que chamamos de HAS essencial ou primária. As medidas não-farmacológicas para controle de HAS incluem redução de peso, redução de consumo de sal e bebidas alcoólicas, aumento do consumo de frutas e verduras e prática de atividade física regular. O tratamento medicamentoso deve ser individualizado conforme a raça, idade, clínica e risco cardiovascular.

Arterial Hypertension (AH) affects nearly 30% of the world wide population. It can be defined as persistent blood pressure elevation over 140/90 mmHg. In nearly 5-10% of the hypertensive patients, one can identify a secondary cause of HA, however, the most patients have what we define as primary or essential HA. Non-pharmacological treatment for AH control include weight loss, reduction of salt and alcohol intake, increased consumption of fruits and vegetables and regular physical activity. The pharmacological treatment must be individualized according to ethnicity, age, clinic, and cardiovascular risk.

Injúria Renal Aguda (IRA): evolução de um conceito / Acute renal injury (ARI): evolution of a concept

O termo injúria (dano ou lesão) renal aguda é, atualmente, o recomendado para definir alterações agudas na função renal. O último consenso publicado pelo KDIGO utiliza a creatinina sérica e o débito urinário na classificação da síndrome. O artigo é uma revisão sobre aspectos desta síndrome que está relacionada a significativa mortalidade.

Acute kidney injury is the recommended term to define acute changes in renal function. The last KDIGO consensus recommend the use of serum creatinine and the urinary output in its classification. The present paper review some aspects of this syndrome that is associated with significant mortality.