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.

New FIB-4 and NFS cutoffs to guide sequential non-invasive assessment of liver fibrosis by magnetic resonance elastography in NAFLD.

INTRODUCTION AND OBJECTIVES: Liver fibrosis is an important prognosis marker in non-alcoholic fatty liver disease (NAFLD). Biopsy has been considered the gold-standard method for measuring liver fibrosis; however, it is an invasive procedure. Non-invasive diagnostic tools have been developed, such as clinical scores and magnetic resonance elastography (MRE), which is the most accurate non-invasive method to determine liver fibrosis. Thus, the aim was to determine the NAFLD Fibrosis Score (NFS) and the Fibrosis-4 Score (FIB-4) cut-off points that best identify NAFLD patients at risk for developing liver fibrosis. PATIENTS AND METHODS: Single-center cross-sectional study with prospective recruitment of NAFLD (training-cohort) and MAFLD (validation-cohort) patients undergoing MRE. The NFS and the FIB-4 cut-off points that best-differentiated patients with fibrosis, using the MRE as the standard method, were determined. RESULTS: Two cohorts were analyzed, a training cohort that included the initial 183 patients with NAFLD and a validation cohort that included 289 patients. In the training cohort, 60.1% had mild steatosis and 11.5% had liver fibrosis ≥ F1 by MRE. ROC curves were developed for FIB-4 and NFS, and the cut-off points chosen were 1.505 (sensitivity=85% and specificity=86%) for FIB-4 and -0.835 (sensitivity=100% and specificity=70%) for NFS, showing greater specificity than the cut-off points currently used (51% and 76%, respectively). The two cohorts exhibited similar characteristics and similar sensitivity and specificity results for the chosen cut-off points. CONCLUSIONS: This study has shown cut-off points with greater specificity and excellent sensitivity to guide the indication for further liver evaluation by MRE in NAFLD patients.

Magnetic resonance imaging findings in placenta accreta spectrum disorders: pictorial essay.

Placenta accreta spectrum disorders are characterized by abnormal adhesion of the placenta that can be subdivided into three categories according to degree of invasion: placenta accreta (passing through the decidua basalis and adhering to the myometrium); placenta increta (penetrating the myometrium); and placenta percreta (invading the uterine serosa or adjacent tissues or organs). The incidence of placenta accreta has increased significantly in recent decades, mainly because of an increase in the rates of cesarean section, which is its main risk factor. Accurate prenatal identification makes it possible to institute the ideal treatment with a multidisciplinary team, significantly minimizing maternal morbidity and mortality. The examinations of choice are ultrasound and magnetic resonance imaging (MRI). When the ultrasound evaluation is inconclusive, as well as when the patient has risk factors for the condition or the placenta is in a posterior location, MRI is indicated. In cases of placental invasion of the adjacent pelvic organs, MRI is also preferable because it provides a broader field of view, which improves surgical planning. Numerous features of placenta accreta spectrum disorders are discernible on MRI, including dark intraplacental bands, uterine bulging, and heterogeneous placenta. Knowledge of these findings and the combination of two or more of them increase confidence in the diagnosis.

Acretismo placentário é uma condição caracterizada pela implantação anormal da placenta, que pode ser subdividida em três espectros de acordo com o seu grau de invasão: placenta acreta (ultrapassa a decídua basal e adere ao miométrio), placenta increta (penetra o miométrio) e placenta percreta (invasão da serosa uterina ou de tecidos/órgãos adjacentes). A incidência de acretismo placentário aumentou significativamente nas últimas décadas, principalmente em função da elevação das taxas de cesarianas, sendo este o seu principal fator de risco. A sua identificação pré-natal precisa permite um tratamento ideal com equipe multidisciplinar, minimizando significativamente a morbimortalidade materna. Os exames de escolha são a ultrassonografia e a ressonância magnética (RM), sendo a RM um método complementar indicado quando a avaliação ultrassonográfica é duvidosa, para pacientes com fatores de risco para acretismo placentário ou quando a placenta tem localização posterior. A RM é preferível também para avaliar invasão de órgãos adjacentes, oferecendo um campo de visão mais amplo, o que melhora o planejamento cirúrgico. Diversas características na RM são descritas no acretismo placentário, incluindo bandas hipointensas em T2 intraplacentárias, protuberância uterina anormal e heterogeneidade placentária. O conhecimento desses achados e a combinação de mais de um critério aumentam a confiabilidade do diagnóstico.

Achados na ressonância magnética do espectro do acretismo placentário: ensaio iconográfico / Magnetic resonance imaging findings in placenta accreta spectrum disorders: pictorial essay

Resumo Acretismo placentário é uma condição caracterizada pela implantação anormal da placenta, que pode ser subdividida em três espectros de acordo com o seu grau de invasão: placenta acreta (ultrapassa a decídua basal e adere ao miométrio), placenta increta (penetra o miométrio) e placenta percreta (invasão da serosa uterina ou de tecidos/órgãos adjacentes). A incidência de acretismo placentário aumentou significativamente nas últimas décadas, principalmente em função da elevação das taxas de cesarianas, sendo este o seu principal fator de risco. A sua identificação pré-natal precisa permite um tratamento ideal com equipe multidisciplinar, minimizando significativamente a morbimortalidade materna. Os exames de escolha são a ultrassonografia e a ressonância magnética (RM), sendo a RM um método complementar indicado quando a avaliação ultrassonográfica é duvidosa, para pacientes com fatores de risco para acretismo placentário ou quando a placenta tem localização posterior. A RM é preferível também para avaliar invasão de órgãos adjacentes, oferecendo um campo de visão mais amplo, o que melhora o planejamento cirúrgico. Diversas características na RM são descritas no acretismo placentário, incluindo bandas hipointensas em T2 intraplacentárias, protuberância uterina anormal e heterogeneidade placentária. O conhecimento desses achados e a combinação de mais de um critério aumentam a confiabilidade do diagnóstico.

Abstract Placenta accreta spectrum disorders are characterized by abnormal adhesion of the placenta that can be subdivided into three categories according to degree of invasion: placenta accreta (passing through the decidua basalis and adhering to the myometrium); placenta increta (penetrating the myometrium); and placenta percreta (invading the uterine serosa or adjacent tissues or organs). The incidence of placenta accreta has increased significantly in recent decades, mainly because of an increase in the rates of cesarean section, which is its main risk factor. Accurate prenatal identification makes it possible to institute the ideal treatment with a multidisciplinary team, significantly minimizing maternal morbidity and mortality. The examinations of choice are ultrasound and magnetic resonance imaging (MRI). When the ultrasound evaluation is inconclusive, as well as when the patient has risk factors for the condition or the placenta is in a posterior location, MRI is indicated. In cases of placental invasion of the adjacent pelvic organs, MRI is also preferable because it provides a broader field of view, which improves surgical planning. Numerous features of placenta accreta spectrum disorders are discernible on MRI, including dark intraplacental bands, uterine bulging, and heterogeneous placenta. Knowledge of these findings and the combination of two or more of them increase confidence in the diagnosis.

Imaging findings of melanoma metastasis in the gallbladder.

We present the case of a 40-year-old male with a previous diagnosis of cutaneous melanoma in the dorsal region, with metastases in axillary and mesenteric lymph nodes and in the central nervous system. He presented focal areas of increased radiopharmaceutical uptake in the topography of the gallbladder infundibulum on a control positron emission tomography/computed tomography (PET/CT), which corresponded to a nodular lesion in an abdominal ultrasound.

Functional magnetic resonance imaging in oncology: state of the art / Ressonância magnética funcional na oncologia: estado da arte

In the investigation of tumors with conventional magnetic resonance imaging, both quantitative characteristics, such as size, edema, necrosis, and presence of metastases, and qualitative characteristics, such as contrast enhancement degree, are taken into consideration. However, changes in cell metabolism and tissue physiology which precede morphological changes cannot be detected by the conventional technique. The development of new magnetic resonance imaging techniques has enabled the functional assessment of the structures in order to obtain information on the different physiological processes of the tumor microenvironment, such as oxygenation levels, cellularity and vascularity. The detailed morphological study in association with the new functional imaging techniques allows for an appropriate approach to cancer patients, including the phases of diagnosis, staging, response evaluation and follow-up, with a positive impact on their quality of life and survival rate.

O estudo convencional dos tumores por ressonância magnética avalia tanto características morfológicas e quantitativas, tais como tamanho, edema, necrose e presença de metástases, quanto características qualitativas, como grau de realce pós-contraste. Entretanto, as mudanças no metabolismo celular e na fisiologia tecidual que precedem as mudanças morfológicas não são detectadas com a técnica convencional. O desenvolvimento de novas técnicas de imagem por ressonância magnética possibilitou a avaliação funcional das estruturas, no intuito de obter informações sobre os diferentes processos fisiológicos do microambiente tumoral, como níveis de oxigenação, celularidade e vascularização. O detalhado estudo morfológico, aliado às novas técnicas de imagem funcional, permite que o paciente oncológico seja adequadamente avaliado, incluindo as etapas de diagnóstico, estadiamento, avaliação de resposta e seguimento, com impacto positivo na qualidade de vida e taxa de sobrevida.

Functional magnetic resonance imaging in oncology: state of the art.

In the investigation of tumors with conventional magnetic resonance imaging, both quantitative characteristics, such as size, edema, necrosis, and presence of metastases, and qualitative characteristics, such as contrast enhancement degree, are taken into consideration. However, changes in cell metabolism and tissue physiology which precede morphological changes cannot be detected by the conventional technique. The development of new magnetic resonance imaging techniques has enabled the functional assessment of the structures in order to obtain information on the different physiological processes of the tumor microenvironment, such as oxygenation levels, cellularity and vascularity. The detailed morphological study in association with the new functional imaging techniques allows for an appropriate approach to cancer patients, including the phases of diagnosis, staging, response evaluation and follow-up, with a positive impact on their quality of life and survival rate.

O estudo convencional dos tumores por ressonância magnética avalia tanto características morfológicas e quantitativas, tais como tamanho, edema, necrose e presença de metástases, quanto características qualitativas, como grau de realce pós-contraste. Entretanto, as mudanças no metabolismo celular e na fisiologia tecidual que precedem as mudanças morfológicas não são detectadas com a técnica convencional. O desenvolvimento de novas técnicas de imagem por ressonância magnética possibilitou a avaliação funcional das estruturas, no intuito de obter informações sobre os diferentes processos fisiológicos do microambiente tumoral, como níveis de oxigenação, celularidade e vascularização. O detalhado estudo morfológico, aliado às novas técnicas de imagem funcional, permite que o paciente oncológico seja adequadamente avaliado, incluindo as etapas de diagnóstico, estadiamento, avaliação de resposta e seguimento, com impacto positivo na qualidade de vida e taxa de sobrevida.

Pattern of P50 suppression deficit in patients with epilepsy and individuals with schizophrenia.

OBJECTIVE: To identify P50 suppression in patients with epilepsy, to investigate the effect of seizure control on P50 suppression, and to compare epilepsy patients with individuals with schizophrenia and healthy volunteers. METHOD: P50 evoked potential parameters and P50 suppression were studied crossectionally in patients with uncontrolled or controlled epilepsy, in individuals with schizophrenia and in healthy volunteers. RESULTS: Individuals with schizophrenia had significantly smaller conditioning stimulus (S1) amplitude, and patients with epilepsy had larger test stimulus (S2) amplitude. Mean S2/S1 ratio was 0.71 ± 0.33 for patients with uncontrolled epilepsy; 0.68 ± 0.36 for patients with controlled epilepsy; 0.96 ± 0.47 for individuals with schizophrenia, and 0.42 ± 0.24 for healthy volunteers. CONCLUSION: The sensory filter of patients with epilepsy is altered, and this alteration is not associated with seizure control. Also, it works differently from the sensory filter of individuals with schizophrenia.

Pattern of P50 suppression deficit in patients with epilepsy and individuals with schizophrenia / Padrão do déficit de supressão do P50 em pacientes com epilepsia e em indivíduos com esquizofrenia

OBJECTIVE: To identify P50 suppression in patients with epilepsy, to investigate the effect of seizure control on P50 suppression, and to compare epilepsy patients with individuals with schizophrenia and healthy volunteers. METHOD: P50 evoked potential parameters and P50 suppression were studied crossectionally in patients with uncontrolled or controlled epilepsy, in individuals with schizophrenia and in healthy volunteers. RESULTS: Individuals with schizophrenia had significantly smaller conditioning stimulus (S1) amplitude, and patients with epilepsy had larger test stimulus (S2) amplitude. Mean S2/S1 ratio was 0.71±0.33 for patients with uncontrolled epilepsy; 0.68±0.36 for patients with controlled epilepsy; 0.96±0.47 for individuals with schizophrenia, and 0.42±0.24 for healthy volunteers. CONCLUSION: The sensory filter of patients with epilepsy is altered, and this alteration is not associated with seizure control. Also, it works differently from the sensory filter of individuals with schizophrenia.

OBJETIVO: Identificar se existe déficit de supressão do P50 em pacientes com epilepsia, verificar a influência do controle das crises nesse déficit, comparando com pacientes com esquizofrenia e com voluntários saudáveis. MÉTODO: Os parâmetros do potencial evocado P50 e sua supressão foram estudados, com um corte transversal, em pacientes com epilepsia controlada ou não, esquizofrenia e em voluntários saudáveis. RESULTADOS: Indivíduos com esquizofrenia apresentam uma amplitude de S1 significativamente menor que os demais, sendo que os pacientes com epilepsia apresentavam uma resposta S2 de maior amplitude. A média da razão S2/S1 foi de 0,71±0,33 nos pacientes com epilepsia não controlada; 0,68±0,36 naqueles com epilepsia controlada; 0,96±0,47 nos com esquizofrenia e 0,42±0,24 nos controles normais. CONCLUSÃO: O filtro sensitivo de pacientes com epilepsia é alterado, e essa alteração não está associada com o controle das crises. Além disso, ele funciona de forma diferente do filtro sensitivo dos indivíduos com esquizofrenia.

Are MPS II heterozygotes actually asymptomatic? A study based on clinical and biochemical data, X-inactivation analysis and imaging evaluations.

For some X-linked disorders the expressivity and penetrance in females are almost similar to those ones found in males. For mucopolysaccharidosis type II (MPS II), there are no studies in the literature trying to identify subtle signs and symptoms of this disease in heterozygotes. The objective of this study was to compare heterozygotes and non-heterozygotes for MPS II, in order to test the hypothesis that heterozygotes may present subtle manifestations of the disease. In this observational and transversal study we collected data on 40 Brazilian women with a positive familial history for MPS II that included clinical and physical exam, karyotype, pattern of X-inactivation, iduronate-2-sulfatase (IDS) activity in leukocytes and plasma, urinary glycosaminoglycans levels, computerized tomography scans (CT) of abdomen and spine, and brain magnetic resonance imaging. The Results showed the following: According to DNA analysis, 22 women were classified as heterozygote and 18 as non-heterozygotes. We did not find any abnormality on physical examination, karyotype, or spine CT. Also the pattern of X-inactivation was not different between the groups. Applying the Bonferroni's correction, both groups were found to differ only in relation to IDS activity in plasma and in leukocyte, which were lower in heterozygotes. In our investigation we did not find any evidence of subtle clinical manifestations of MPS II in heterozygotes. Our findings suggest there is no relation between the absence of clinical signs in these women and the occurrence of a favorable skewing pattern of X-inactivation.

Does caffeine change the effect of sleep deprivation on moderate to severe depressed patients?

INTRODUCTION: Sleep deprivation (SD) has been used as an alternative approach to treat major depressive disorder (MDD). Caffeine, due to its stimulating effect, could be an alternative to promote sleep deprivation. However, there are no data about its potential influence on the antidepressive effect of SD. The objective of this study is to assess the effect of caffeine on SD in non-psychotic patients with moderate to severe unipolar depression. METHODS: Randomized, double-blind, crossover clinical trial comparing caffeine and placebo in moderate to severe depressed patients who underwent total sleep deprivation (SD). The patients were assessed with items of the Bond-Lader scale, the 6-item Hamilton Depression Rating Scale (HAMD-6), and the Clinical Global Impression (CGI)-Severity/Improvement. RESULTS: Twenty patients participated in this study. The patients who consumed caffeine presented the same level of energy before and after sleep deprivation (lethargic-energetic item of the Bond-Lader scale), while the patients in the placebo group had a reduced level of energy after sleep deprivation (p=0.0045). There was no difference between the caffeine and placebo groups in the other items of the Bond-Lader scale. CONCLUSION: The combined use of caffeine and SD can be a useful strategy to keep the patient awake without impairing the effect of SD on depressed outpatients. However, further studies involving patients who have responded to SD are needed in order to verify if caffeine also does not interfere with the results in this group.

Caffeine modulates P50 auditory sensory gating in healthy subjects.

The P50 suppression paradigm is an index of sensory gating assumed to reflect an inhibitory process. Adenosine is a neuromodulator with mostly inhibitory activity that is released by physiological stimuli and can be blocked by non-selective adenosine receptor antagonists such as theophylline and caffeine. A previous study showed that a single dose of theophylline decreased P50 suppression in healthy volunteers. Here we investigated the effect of caffeine (0, 100, 200 and 400 mg p.o.) on P50 sensory gating in 24 healthy volunteers (15 habitual caffeine high-users and 9 low-users). The 200 and 400 mg doses reduced P50 gating, whereas 100 mg produced a non-significant effect. The effect of caffeine was independent of gender and habitual caffeine intake. High caffeine users also showed baseline differences, with lower S(2) amplitudes compared to low-users. These results reinforce the participation of adenosine in the modulation of P50 sensory gating and suggest that caffeine ingestion should be controlled for in the P50 sensory gating paradigm.

Geradores do P50: estudo com pacientes epilépticos, submetidos á amígdala-hipocampectomia / P50 generators: study with epileptic patients submitted on the amigadala-hippocampectomy

Estudar o envolvimento do hipocampo na gênese dopotencial evocado P50 e da supressão do mesmo em pacientes com epilepsia submetidos a tratamento cirúrgico. Foi realizado um estudo transversal com grupo de controle de comparação. Excluíram-se indivíduos com outra patologia neurológica ou psiquiátrica, hipoacusia auditiva, história familiar de transtornos psicóticos, uso de antipsicóticos atípicos ou de drogas ilícitas no último mês. Os indivíduos foram separados em dois grupos: grupo 1 (n=34) - amígdala-hipocampectomia; grupo 2 (n=40) - controles. Foi realizado, em todos os participantes, o potencial evocado auditivo de m,édia latência P50. Consideraram-se variáveis de comparação