Association between Leukemic Evolution and Uncommon Chromosomal Alterations in Pediatric Myelodysplastic Syndrome.

Background: Pediatric myelodysplastic syndrome (pMDS) is a group of rare clonal neoplasms with a difficult diagnosis and risk of progression to acute myeloid leukemia (AML). The early stratification in risk groups is essential to choose the treatment and indication for allogeneic hematopoietic stem cell transplantation (HSCT). According to the Revised International Prognostic Scoring System, cytogenetic analysis has demonstrated an essential role in diagnosis and prognosis. In pMDS, abnormal karyotypes are present in 30-50% of the cases. Monosomy 7 is the most common chromosomal alteration associated with poor prognosis. However, the rarity of specific cytogenetic alterations makes its prognosis uncertain. Thus, this study aimed to describe uncommon cytogenetic alterations in a cohort of 200 pMDS patients and their association with evolution to AML. Methods: The cytogenetic analysis was performed in 200 pMDS patients by G-banding and fluorescence in situ hybridization between 2000 to 2022. Results: Rare chromosome alterations were observed in 7.5% (15/200) of the cases. These chromosome alterations were divided into four cytogenetic groups: hyperdiploidy, biclonal chromosomal alterations, translocations, and uncommon deletions representing 33.3%, 33.3%, 20%, and 13.3%, respectively. Most of these patients (10/15) were classified with advanced MDS (MDS-EB and MDS/AML) and the initial subtype was present in five patients (RCC). The leukemic evolution was observed in 66.66% (10/15) of the patients. Most patients had poor clinical outcomes and they were indicated for HSCT. Conclusion: The study of uncommon cytogenetic alterations in pMDS is important to improve the prognosis and guide early indication of HSCT.

Treatment patterns in metastatic bladder cancer in Japan: results of the CancerMPact® survey 2020.

Aim: To assess physician-reported treatment of metastatic bladder cancer in Japan. Methods: 76 physicians completed the CancerMPact® survey in July 2020, considering patients treated within 6 months. Results: Physicians treated a mean of 38.1 patients per month. Of cisplatin-eligible and -ineligible patients, 97.6 and 89.3%, respectively, received first-line platinum-based therapy, most commonly cisplatin plus gemcitabine (72.9%) and carboplatin plus gemcitabine (59.7%). 1.6 and 5.6% received first-line immune checkpoint inhibitors, respectively. 48.4 and 45.0%, respectively, progressed and received second-line therapy, most commonly with pembrolizumab (61.7%). Conclusion: In 2020, most patients with metastatic bladder cancer in Japan received first-line platinum-based chemotherapy; however, >50% received no subsequent treatment, highlighting the need for new treatment regimens to improve outcomes and maximize first-line treatment benefits.

In 2020, researchers surveyed 76 Japanese doctors who specialized in bladder and urinary system disorders about how they treated people with bladder cancer. Cisplatin, a type of chemotherapy drug, was the most common first treatment. For people who were unable to receive cisplatin, doctors often prescribed a similar chemotherapy drug called carboplatin. Just under half of the people received a second treatment for their cancer. New treatments are now available for bladder cancer, including the immunotherapy drug avelumab, which is given to people whose cancer stops growing or shrinks with their first chemotherapy treatment. More research is needed to better understand how bladder cancer is treated in Japan, including how new treatments are used.

Physician reported treatment patterns and outcomes in metastatic bladder cancer in the USA: the CancerMPact® Survey 2020.

Aim: This study assessed physician-reported treatment patterns for metastatic bladder cancer. Materials & methods: A total of 106 USA-based physicians were surveyed in 2020 using the CancerMPact® online survey. Results: Among cisplatin-eligible patients, 86.1% received first-line (1L) platinum-containing chemotherapy, most commonly cisplatin plus gemcitabine, and 9.8% received immune checkpoint inhibitor monotherapy. Among cisplatin-ineligible patients, 46.5% received 1L platinum-containing chemotherapy, most commonly carboplatin plus gemcitabine and 46.2% received 1L immune checkpoint inhibitor therapy. Approximately 44% of patients who received 1L treatment received second-line (2L) therapy after progression. Conclusion: Platinum-containing chemotherapy was the most widely reported 1L treatment approach. A high proportion of patients received no 2L therapy. Validation in an updated dataset is warranted following the practice-changing approvals of avelumab 1L maintenance and additional 2L options.

In 2020, researchers surveyed 106 US doctors about how they treated people with advanced bladder cancer. Cisplatin, a chemotherapy drug, was the most common first treatment that was given to patients with advanced bladder cancer. For people who were unable to receive cisplatin, doctors preferred to prescribe a similar chemotherapy drug called carboplatin or an immunotherapy drug. Immunotherapies help the body's immune system to fight cancer cells. Most people treated by the surveyed doctors did not receive a second treatment if their cancer got worse. New treatments are now available for bladder cancer, such as the immunotherapy, avelumab. Avelumab is given after chemotherapy to try and stop the cancer from getting worse or coming back. More research is needed to further understand how bladder cancer is treated.

Prognostic Factors in Children and Adolescents with Lymphomas and Vertical Transmission of HIV in Rio de Janeiro, Brazil: A Multicentric Hospital-Based Survival Analysis Study.

Lymphomas related to HIV are generally aggressive and have a poor prognosis, despite the use of combined antiretroviral therapy (cART) and effective chemotherapy treatment. To determine survival and prognostic factors in children and adolescents living with HIV (CLWH) in Rio de Janeiro (RJ), Brazil, who developed lymphomas, we performed a retrospective and observational study of vertically infected CLWH aged from 0 to 20 incomplete years during1995 to 2018 at five reference centers for cancer and HIV/AIDS treatment. Of the 25 lymphomas, 19 were AIDS-defining malignancies (ADM) and 6 were non-AIDS-defining malignancies (NADM). The 5-year overall survival (OS) and 5-year event-free survival (EFS) probabilities were both 32.00% (95% CI = 13.72-50.23%), and the 5-year disease-free survival (DFS) probability was 53.30% (95% CI = 28.02-78.58%). In the multivariate Cox regression analysis, performance status 4 (PS 4) was considered a poor prognostic factor for OS (HR 4.85, 95% CI = 1.81-12.97, p = 0.002) and EFS (HR 4.95, 95% CI = 1.84-13.34, p = 0.002). For the DFS, higher CD4+ T-cell counts were considered a better prognostic factor (HR 0.86, 95% CI = 0.76-0.97, p = 0.017) in the multivariate Cox regression analysis. This study demonstrates, for the first time, survival and prognostic factors for CLWH who developed lymphomas in RJ, Brazil.

A Novel Constitutional t(3;8)(p26;q21) and ANKRD26 and SRP72 Variants in a Child with Myelodysplastic Neoplasm: Clinical Implications.

BACKGROUND: Childhood myelodysplastic neoplasm (cMDS) often raises concerns about an underlying germline predisposition, and its verification is necessary to guide therapeutic choice and allow family counseling. Here, we report a novel constitutional t(3;8)(p26;q21) in a child with MDS, inherited from the father, the ANKRD26 and SRP72 variants from the maternal origin, and the acquisition of molecular alterations during MDS evolution. CASE PRESENTATION: A 4-year-old girl showed repeated infections and severe neutropenia. Bone marrow presented hypocellularity with dysplastic features. The patient had a t(3;8)(p26;q21)c identified by G-banding and FISH analysis. The family nucleus investigation identified the paternal origin of the chromosomal translocation. The NGS study identified ANKRD26 and SRP72 variants of maternal origin. CGH-array analysis detected alterations in PRSS3P2 and KANSL genes. Immunohistochemistry showed abnormal p53 expression during the MDS evolution. CONCLUSION: This study shows for the first time, cytogenetic and genomic abnormalities inherited from the father and mother, respectively, and their clinical implications. It also shows the importance of investigating patients with constitutional cytogenetic alterations and/or germline variants to provide information to their family nucleus for genetic counseling and understanding of the pathogenesis of childhood MDS.

Systematic literature review and meta-analysis of cardiovascular risk factor management in selected Asian countries.

Aim: There is a need to understand the management status of hypertension, dyslipidemia/hypercholesterolemia, and diabetes mellitus in the Asia-Pacific region (APAC). Methods: We conducted a systematic literature review and meta-analysis to summarize the awareness, treatment, and/or control rates of these risk factors in adults across 11 APAC countries/regions. Results: We included 138 studies. Individuals with dyslipidemia had the lowest pooled rates compared with those with other risk factors. Levels of awareness with diabetes mellitus, hypertension, and hypercholesterolemia were comparable. Individuals with hypercholesterolemia had a statistically lower pooled treatment rate but a higher pooled control rate than those with hypertension. Conclusion: The management of hypertension, dyslipidemia, and diabetes mellitus was suboptimal in these 11 countries/regions.

Polygenic risk score for attention-deficit/hyperactivity disorder and brain functional networks segregation in a community-based sample.

Neuroimaging studies suggest that brain development mechanisms might explain at least some behavioural and cognitive attention-deficit/hyperactivity disorder (ADHD) symptoms. However, the putative mechanisms by which genetic susceptibility factors influence clinical features via alterations of brain development remain largely unknown. Here, we set out to integrate genomics and connectomics tools by investigating the associations between an ADHD polygenic risk score (ADHD-PRS) and functional segregation of large-scale brain networks. With this aim, ADHD symptoms score, genetic and rs-fMRI (resting-state functional magnetic resonance image) data obtained in a longitudinal community-based cohort of 227 children and adolescents were analysed. A follow-up was conducted approximately 3 years after the baseline, with rs-fMRI scanning and ADHD likelihood assessment in both stages. We hypothesised a negative correlation between probable ADHD and the segregation of networks involved in executive functions, and a positive correlation with the default-mode network (DMN). Our findings suggest that ADHD-PRS is correlated with ADHD at baseline, but not at follow-up. Despite not surviving for multiple comparison correction, we found significant correlations between ADHD-PRS and segregation of cingulo-opercular networks and DMN at baseline. ADHD-PRS was negatively correlated with the segregation level of cingulo-opercular networks but positively correlated with the DMN segregation. These directions of associations corroborate the proposed counter-balanced role of attentional networks and DMN in attentional processes. However, the association between ADHD-PRS and brain networks functional segregation was not found at follow-up. Our results provide evidence for specific influences of genetic factors on development of attentional networks and DMN. We found significant correlations between polygenic risk score for ADHD (ADHD-PRS) and segregation of cingulo-opercular networks and default-mode network (DMN) at baseline. ADHD-PRS was negatively correlated with the segregation level of cingulo-opercular networks but positively correlated with the DMN segregation.

Incidence and Clinical Description of Lymphomas in Children and Adolescents with Vertical Transmission of HIV in Rio de Janeiro, Brazil, in Pre- and Post-Combined Antiretroviral Therapy Eras: A Multicentric Hospital-Based Survival Analysis Study.

The incidence of cancer in children living with HIV (CLWH) is high and lymphomas are the most common type of cancer in this population. The combined antiretroviral therapy (cART) changed the natural history of HIV infection. To determine the incidence and profile of these CLWH malignancies in Rio de Janeiro (RJ), Brazil, we conducted a retrospective and observational study of vertically infected CLWH, ranging from 0−20 incomplete years, from 1995 to 2018, at five reference centers. The study period was divided into three eras in accordance with the widespread use of cART in Brazil. 1306 patients were included. Of the 25 lymphomas found, 19 were AIDS-defining malignancies (ADM); 6 were non-AIDS-defining malignancies (NADM). The incidence rate (IR) of lymphoma developing was 1.70 per 1000 children-year (95% CI 1.09−2.50). ADM development IR decreased from 2.09−1.75−0.19 per 1000 children-year (p < 0.001) through cART eras. Cumulative Nelson−Aalen hazards of developing ADM over a 20-year period were 3.73% in the Early-cART era, 3.07% in the Mid-cART era, and 0.32% in the Late-cART era (p = 0.013). This study demonstrates the IR of lymphoma in CLWH in RJ, Brazil, as well as the benefit of cART in reducing ADM and death occurrence in the Post-cART era.

Associations between Family Functioning and Maternal Behavior on Default Mode Network Connectivity in School-Age Children.

Background: Most early children's experiences will occur in a family context; therefore, the quality of this environment is critical for development outcomes. Not many studies have assessed the correlations between brain functional connectivity (FC) in important areas such as the default mode network (DMN) and the quality of parent-child relationships in school-age children and early adolescence. The quality of family relationships and maternal behavior have been suggested to modulate DMN FC once they act as external regulators of children's affect and behavior. Objective: We aimed to test the associations between the quality of family environment/maternal behavior and FC within the DMN of school-age children. Method: Resting-state, functional magnetic resonance imaging data, were collected from 615 children (6-12 age range) enrolled in the Brazilian High-Risk Cohort (HRC) study. We assessed DMN intra-connectivity between the medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), and inferior parietal lobule (IPL-bilateral) regions. The family functioning was assessed by levels of family cohesiveness and conflict and by maternal behavior styles such as maternal responsiveness, maternal stimulus to the child's autonomy, and maternal overprotection. The family environment was assessed with the Family Environment Scale (FES), and maternal behavior was assessed by the mother's self-report. Results: We found that the quality of the family environment was correlated with intra-DMN FC. The more conflicting the family environment was, the greater the FC between the mPFC-left IPL (lIPL), while a more cohesive family functioning was negatively correlated with FC between the PCC-lIPL. On the other hand, when moderated by a positive maternal behavior, cohesive family functioning was associated with increased FC in both regions of the DMN (mPFC-lIPL and PCC-lIPL). Conclusions: Our results highlight that the quality of the family environment might be associated with differences in the intrinsic DMN FC.

Chronic Granulomatous Disease and Myelodysplastic Syndrome in a Patient with a Novel Mutation in CYBB.

Chronic Granulomatous Disease (CGD) is an inborn error of immunity characterized by impaired phagocyte function, recurrent fungal and bacterial infections and granuloma formation in multiple organs. Pediatric myelodysplastic Syndrome (MDS) is a rare hematological stem cell disease that leads to an ineffective hematopoiesis with variable risk of evolution to acute leukemias. Both disorders are rare and have distinct pathophysiologic mechanisms, with no known association. A 7-month-old boy presenting with recurrent infections and anemia at age 2 months underwent immunological, hematological and genetic investigation that culminated in the diagnosis of both CGD and MDS. Next generation sequencing was performed and identified a silent variant predicted as of Uncertain Significance, located in the splicing site at the end of exon 5 in CYBB. CYBB variants account for at least two thirds of CGD cases, but no previous descriptions of this variant were found in ClinVar or The Human Gene Mutation Database (HGMD) databases. We were able to demonstrate an exon 5 skipping on the proband's cDNA, which strongly suggests the disruption of the NADPH oxidase complex, abrogating the formation of reactive oxygen species from neutrophils. Moreover, erythroid cell lineage could be also affected by NADPH oxidase complex damages. Further investigation is needed to evaluate the potential effect of CYBB gene alterations in hematopoiesis, as well as in MDS and CGD association.

Regulatory aspects and evidences of melatonin use for sleep disorders and insomnia: an integrative review.

BACKGROUND: Insomnia is a sleep disorder characterized by difficulty of falling asleep or maintaining sleep, which affects different age groups. Currently, melatonin is used as a therapeutic treatment in cases of insomnia in children, adults, and elderly people. OBJECTIVE: To evaluate the effectiveness of melatonin in sleep disorders, its dosage, potential adverse effects, as well as labeling laws and regulations in Brazil. METHODS: This integrative review was carried out using the Cochrane Library, Medline (Pubmed), and Science Direct databases. Twenty-five articles and three documents available on the Brazilian Society of Endocrinology and Metabology (SBEM) and National Health Surveillance Agency (ANVISA) websites published between 2015 and 2020 were selected to be evaluated in full. RESULTS: It was found that in most of the selected articles the use of melatonin reduces sleep latency. The effective melatonin doses varied according to each age group, from 0.5 to 3 mg in children, 3 to 5 mg in adolescents, 1 to 5 mg in adults, and 1 to 6 mg in elderly people. Side effects are mild when taking usual doses. In Brazil, no registered drug and current regulation on the use and marketing of melatonin has been identified. CONCLUSION: The use of melatonin is an alternative therapy that can be used for sleeping disorders. According to the evidences found, it did not demonstrate toxicity or severe side effects, nor dependence even when administered at high doses, suggesting that it is a safe medication to treat patients of different ages suffering from sleeping disorders.

Long-term stability of the cortical volumetric profile and the functional human connectome throughout childhood and adolescence.

There is compelling evidence showing that between-subject variability in several functional and structural brain features is sufficient for unique identification in adults. However, individuation of brain functional connectomes depends on the stabilization of neurodevelopmental processes during childhood and adolescence. Here, we aimed to (1) evaluate the intra-subject functional connectome stability over time for the whole brain and for large scale functional networks and (2) determine the long-term identification accuracy or 'fingerprinting' for the cortical volumetric profile and the functional connectome. For these purposes, we analysed a longitudinal cohort of 239 children and adolescents scanned in two sessions with an interval of approximately 3 years (age range 6-15 years at baseline and 9-18 years at follow-up). Corroborating previous results using short between-scan intervals in children and adolescents, we observed a moderate identification accuracy (38%) for the whole functional profile. In contrast, identification accuracy using cortical volumetric profile was 95%. Among the large-scale networks, the default-mode (26.8%), the frontoparietal (23.4%) and the dorsal-attention (27.6%) networks were the most discriminative. Our results provide further evidence for a protracted development of specific individual structural and functional connectivity profiles.

Regulatory aspects and evidences of melatonin use for sleep disorders and insomnia: an integrative review / Aspectos regulatórios e evidências do uso de melatonina em distúrbio do sono e insônia: uma revisão integrativa

ABSTRACT Background: Insomnia is a sleep disorder characterized by difficulty of falling asleep or maintaining sleep, which affects different age groups. Currently, melatonin is used as a therapeutic treatment in cases of insomnia in children, adults, and elderly people. Objective: To evaluate the effectiveness of melatonin in sleep disorders, its dosage, potential adverse effects, as well as labeling laws and regulations in Brazil. Methods: This integrative review was carried out using the Cochrane Library, Medline (Pubmed), and Science Direct databases. Twenty-five articles and three documents available on the Brazilian Society of Endocrinology and Metabology (SBEM) and National Health Surveillance Agency (ANVISA) websites published between 2015 and 2020 were selected to be evaluated in full. Results: It was found that in most of the selected articles the use of melatonin reduces sleep latency. The effective melatonin doses varied according to each age group, from 0.5 to 3 mg in children, 3 to 5 mg in adolescents, 1 to 5 mg in adults, and 1 to 6 mg in elderly people. Side effects are mild when taking usual doses. In Brazil, no registered drug and current regulation on the use and marketing of melatonin has been identified. Conclusion: The use of melatonin is an alternative therapy that can be used for sleeping disorders. According to the evidences found, it did not demonstrate toxicity or severe side effects, nor dependence even when administered at high doses, suggesting that it is a safe medication to treat patients of different ages suffering from sleeping disorders.

RESUMO Antecedentes: Insônia é um distúrbio do sono caracterizado por dificuldade de iniciar e manter o sono, afetando diferentes faixas etárias. Atualmente, a melatonina é utilizada no tratamento de insônia em crianças, adultos e idosos. Objetivo: Avaliar a eficácia da melatonina nos distúrbios do sono, posologia e potenciais efeitos adversos, bem como a regulamentação vigente no Brasil. Métodos: Trata-se de uma revisão integrativa, os artigos foram identificados nas bases de dados Cochrane Library, Medline (Pubmed) e Science Direct, totalizando 25 artigos, e foram selecionados três materiais disponíveis no site da Sociedade Brasileira de Endocrinologia e Metabologia e Agência Nacional de Vigilância Sanitária, publicados entre 2015 e 2020. Resultados: Verificou-se na maioria dos artigos selecionados que a melatonina reduz a latência do sono. Quanto as dosagens de melatonina identificou-se variação em cada faixa etária, para crianças de 0,5 a 3mg; adolescentes de 3 a 5mg; adultos de 1 a 5mg e idosos 1 mg a 6 mg demostraram serem eficazes. Em doses habituais os efeitos colaterais são leves. No Brasil, não foi identificado medicamento registrado e regulamentação vigente sobre o uso e comercialização de melatonina. Conclusão: A utilização da melatonina é uma alternativa que pode ser utilizada em distúrbios do sono. De acordo com as evidências encontradas, não demonstrou toxicidade ou efeitos colaterais severos, nem dependência mesmo em doses elevadas, sendo, portanto, segura para tratamento de pacientes desde crianças a idosos que sofrem de distúrbios do sono.

Assessing the educational performance of different Brazilian school cycles using data science methods.

Educational indicators are metrics that assist in assessing the quality of the educational system. They are often associated with economic and social factors suggested to contribute to good school performance, however there is no consensus on the impact of these factors. The main objective of this work was to evaluate the factors related to school performance. Using a data set composed by Brazilian schools' performance (IDEB), socioeconomic and school structure variables, we generated different models. The non-linear model predicted the best performance, measured by the error and determination coefficient metrics. The heterogeneity of the importance of the variable between school cycles and regions of the country was detected, this effect may contribute to the development of public educational policies.

Papez Circuit Gray Matter and Episodic Memory in Amyotrophic Lateral Sclerosis and Behavioural Variant Frontotemporal Dementia.

Amyotrophic lateral sclerosis and behavioural variant frontotemporal dementia are two different diseases recognized to overlap at clinical, pathological and genetic characteristics. Both conditions are traditionally known for relative sparing of episodic memory. However, recent studies have disputed that with the report of patients presenting with marked episodic memory impairment. Besides that, structural and functional changes in temporal lobe regions responsible for episodic memory processing are often detected in neuroimaging studies of both conditions. In this study, we investigated the gray matter features associated with the Papez circuit in amyotrophic lateral sclerosis, behavioural variant frontotemporal dementia and healthy controls to further explore similarities and differences between the two conditions. Our non-demented amyotrophic lateral sclerosis patients showed no episodic memory deficits measured by a short-term delayed recall test while no changes in gray matter of the Papez circuit were found. Compared with the amyotrophic lateral sclerosis group, the behavioural variant frontotemporal dementia group had lower performance on the short-term delayed recall test and marked atrophy in gray matter of the Papez circuit. Bilateral atrophy of entorhinal cortex and mammillary bodies distinguished behavioural variant frontotemporal dementia from amyotrophic lateral sclerosis patients as well as atrophy in left cingulate, left hippocampus and right parahippocampal gyrus. Taken together, our results suggest that sub-regions of the Papez circuit could be differently affected in amyotrophic lateral sclerosis and behavioural variant frontotemporal dementia.

Custo-efetividade e impacto orçamentário da introdução do cabozantinibe no tratamento de carcinoma de células renais avançado no sistema de saúde suplementar no Brasil / Cost-effectiveness and budgetary impact of introducing cabozantinib in the treatment of advanced renal cell carcinoma in the supplementary health system in Brazil

Objetivo: Este trabalho teve por objetivo determinar o custo-efetividade e o impacto orçamentário do cabozantinibe para o sistema de saúde suplementar no Brasil, no tratamento de carcinoma de células renais (RCC) avançado ou metastático, após falha de tratamento com inibidor do fator de crescimento endotelial vascular (VEGF), quando comparado ao atual tratamento aprovado: nivolumabe. Métodos: Foram utilizados custos referentes ao uso de recursos, tratamento médico, eventos adversos e qualidade de vida, calculados por estado de saúde. Foi considerado o tempo horizonte de 20 anos para análise de custo-efetividade e 5 anos para impacto orçamentário, e foi realizado um cenário alternativo comparando o cabozantinibe ao nivolumabe e axitinibe. Resultados: O cabozantinibe apresentou eficácia superior quando comparado ao nivolumabe e ao axitinibe e representa uma redução de custos comparado ao nivolumabe. Em relação aos eventos adversos, o cabozantinibe apresenta redução dos gastos quando comparado ao nivolumabe. Conclusão: Esses resultados mostram um potencial de economia ao sistema de saúde suplementar com a adoção do cabozantinibe no tratamento para RCC avançado ou metastático em segunda linha no Brasil.

Objective: This study aimed to determine the cost-effectiveness and budgetary impact of cabozantinib for the supplementary health system in Brazil, in the treatment of advanced or metastatic renal cell carcinoma (RCC) after treatment failure with vascular endothelial growth factor (VEGF) inhibitor, when compared current approved treatment: nivolumab. Methods: Costs related to the use of resources, medical treatment, adverse events and quality of life were used, calculated by health status. The horizon time of 20 years was considered for cost-effectiveness analysis and 5 years for budgetary impact, and an alternative scenario was carried out comparing cabozantinib to nivolumab and axitinib. Results: Cabozantinib showed superior efficacy when compared to nivolumab and axitinib and represents a cost reduction compared to nivolumab. In relation to adverse events, cabozantinib shows a reduction in costs when compared to nivolumab. Conclusion: These results show a potential savings for the supplementary health system with the adoption of cabozantinib in the treatment for advanced or metastatic second-line RCC in Brazil.

Potential Confounders in the Analysis of Brazilian Adolescent's Health: A Combination of Machine Learning and Graph Theory.

The prevalence of health problems during childhood and adolescence is high in developing countries such as Brazil. Social inequality, violence, and malnutrition have strong impact on youth health. To better understand these issues we propose to combine machine-learning methods and graph analysis to build predictive networks applied to the Brazilian National Student Health Survey (PenSE 2015) data, a large dataset that consists of questionnaires filled by the students. By using a combination of gradient boosting machines and centrality hub metric, it was possible to identify potential confounders to be considered when conducting association analyses among variables. The variables were ranked according to their hub centrality to predict the other variables from a directed weighted-graph perspective. The top five ranked confounder variables were "gender", "oral health care", "intended education level", and two variables associated with nutrition habits-"eat while watching TV" and "never eat fast-food". In conclusion, although causal effects cannot be inferred from the data, we believe that the proposed approach might be a useful tool to obtain novel insights on the association between variables and to identify general factors related to health conditions.

Regional Dynamics of the Resting Brain in Amyotrophic Lateral Sclerosis Using Fractional Amplitude of Low-Frequency Fluctuations and Regional Homogeneity Analyses.

Resting-state functional magnetic resonance imaging has been playing an important role in the study of amyotrophic lateral sclerosis (ALS). Although functional connectivity is widely studied, the patterns of spontaneous neural activity of the resting brain are important mechanisms that have been used recently to study a variety of conditions but remain less explored in ALS. Here we have used fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) to study the regional dynamics of the resting brain of nondemented ALS patients compared with healthy controls. As expected, we found the sensorimotor network with changes in fALFF and ReHo, and also found the default mode network (DMN), frontoparietal network (FPN), and salience network (SN) altered and the cerebellum, although no structural changes between ALS patients and controls were reported in the regions with fALFF and ReHo changes. We show an altered pattern in the spontaneous low-frequency oscillations that is not confined to the motor areas and reveal a more widespread involvement of nonmotor regions, including those responsible for cognition.