Ketogenic diet and metastasis: A critical review of the literature and possible mechanisms.

The ketogenic diet (KD) is a low-carb diet that has been indicated as a possible coadjuvant in cancer therapy, mainly due to its capacity to reduce glycolysis production, inflammation, and oxidative stress. However, KD's role in metastasis remains poorly explored. This study aims to provide a critical review of the literature about KD's efficacy in metastasis therapy and the possible molecular mechanisms behind it. Initially, general concepts on KD and metastasis are discussed. Then, it delves deeper into the main cancer mechanisms explored by KD experimental studies, discussing the central results obtained in metastasis research and their main limiting conditions. Following, there is a critical analysis of clinical trials, including those in the grey literature. In the end, there is a summary of the actual studies' limitations and barriers to future research. To date, it is possible to conclude that there is not enough evidence supporting the efficacy of KD in the treatment of metastasis.

ICD indication in hypertrophic cardiomyopathy: which algorithm to use?

OBJECTIVE: This study aimed to evaluate the agreement in the indication of implantable cardioverter-defibrillators in patients with Hypertrophic cardiomyopathy, as per the 2014 European Society of Cardiology and 2020 American Heart Association recommendations, and evaluate fragmented QRS as a predictor of cardiovascular outcome. METHODS: Retrospective cohort with 81 patients was evaluated between 2019 and 2021. Patients with hypertrophic cardiomyopathy ≥16 years old were included. Exclusion criteria include secondary myocardiopathy and follow-up <1 year. Kappa coefficient was used to determine the agreement. Survival and incidence curves were determined by Kaplan-Meier method. A p<0.05 was considered significant. RESULTS: The fragmented QRS was identified in 44.4% of patients. There were no differences between patients with and without fragmented QRS regarding clinical parameters, echocardiography, fibrosis, and sudden cardiac death risk. During follow-up of 4.8±3.4 years, there was no sudden cardiac death, but 20.6% patients with implantable cardioverter-defibrillator had at least one appropriate shock. Three of the seven appropriate shocks occurred in European Society of Cardiology low- to moderate-risk patients. Three shocks occurred in moderate-risk patients and four in American Heart Association high-risk patients. Overall recommendations agreement was 64% with a kappa of 0.270 (p=0.007). C-statistic showed no differences regarding the incidence of appropriate shock (p=0.644). CONCLUSION: sudden cardiac death risk stratification algorithms present discrepancies in implantable cardioverter-defibrillator indication, both with low accuracy.

ICD indication in hypertrophic cardiomyopathy: which algorithm to use?

SUMMARY OBJECTIVE: This study aimed to evaluate the agreement in the indication of implantable cardioverter-defibrillators in patients with Hypertrophic cardiomyopathy, as per the 2014 European Society of Cardiology and 2020 American Heart Association recommendations, and evaluate fragmented QRS as a predictor of cardiovascular outcome. METHODS: Retrospective cohort with 81 patients was evaluated between 2019 and 2021. Patients with hypertrophic cardiomyopathy ≥16 years old were included. Exclusion criteria include secondary myocardiopathy and follow-up <1 year. Kappa coefficient was used to determine the agreement. Survival and incidence curves were determined by Kaplan-Meier method. A p<0.05 was considered significant. RESULTS: The fragmented QRS was identified in 44.4% of patients. There were no differences between patients with and without fragmented QRS regarding clinical parameters, echocardiography, fibrosis, and sudden cardiac death risk. During follow-up of 4.8±3.4 years, there was no sudden cardiac death, but 20.6% patients with implantable cardioverter-defibrillator had at least one appropriate shock. Three of the seven appropriate shocks occurred in European Society of Cardiology low- to moderate-risk patients. Three shocks occurred in moderate-risk patients and four in American Heart Association high-risk patients. Overall recommendations agreement was 64% with a kappa of 0.270 (p=0.007). C-statistic showed no differences regarding the incidence of appropriate shock (p=0.644). CONCLUSION: sudden cardiac death risk stratification algorithms present discrepancies in implantable cardioverter-defibrillator indication, both with low accuracy.

O Sistema de Saúde japonês e seus mecanismos de enfrentamento à COVID-19 / The Japanese Health System and its coping mechanisms against COVID-19

Introdução: apesar de ser o país de maior média de idade no mundo, o Japão tem se destacado no combate à pandemia da COVID-19 (do inglês Coronavirus Disease 2019) ao apresentar reduzidas taxas de contaminação pelo vírus e de mortalidade. Objetivo: discutir acerca das estratégias em saúde adotadas pelo Japão diante da pandemia da doença da COVID-19, bem como avaliar os dados sobre contaminação e mortalidade japoneses em comparação com os outros quatro países com maior média de idade do mundo (Itália, Alemanha, Portugal e Espanha) e o Brasil. Metodologia: para avaliação das estratégias em saúde japonesas foi realizada busca nas bases de dados: PubMed, Cochrane e Scielo, utilizando-se combinação dos termos "Japão", "covid", "coronavirus" e "sistemas de saúde", nos idiomas Inglês, Espanhol e Português. Os dados de infecção da COVID-19 foram extraídos do site Our World in Data, correspondendo ao período de 25 de janeiro de 2020 a 30 de julho de 2020. Resultados: dentre as medidas adotadas pelo país no enfrentamento à pandemia, destacam-se o diagnóstico e resposta precoces à infecção, o rastreamento de contatos, o diagnóstico precoce e disponibilidade de cuidados intensivos para pacientes graves e estímulo a medidas comportamentais de distanciamento. Dentre os países analisados, o Japão apresenta as menores taxas de contaminação e mortalidade em termos absolutos pela COVID-19. Conclusões: medidas de distanciamento social, diagnóstico e tratamento precoces parecem ter contribuído para o sucesso no combate à COVID-19 no Japão. No período estudado, em milhão de habitantes, o Japão teve 6,13 casos de Covid, enquanto o Brasil apresentou 218,26 casos. Já no número de mortes confirmadas pela doença, o primeiro teve uma taxa de 0,23 enquanto o segundo de 5,16 casos por milhão de habitantes. É possível, a partir do conhecimento dessas medidas, buscar mecanismos semelhantes ao traçar políticas de saúde no enfrentamento de pandemias em outros países (AU)

Introduction: despite being the country with the highest average age globally, Japan has stood out in the fight against the COVID-19 (Coronavirus Disease 2019) pandemic by presenting low contamination rates by the virus and mortality. Objective: we aim to discuss the health strategies adopted by Japan in the face of the COVID-19 disease pandemic, as well as to evaluate data on Japanese contamination and mortality compared to the other four countries with the highest average age in the world (Italy, Germany, Portugal and Spain) and Brazil. Methodology: the search was carried out to evaluate Japanese health strategies by using the following databases: PubMed, Cochrane, and Scielo using a combination of the terms "Japan", "covid", "coronavirus" and "health systems" in English, Spanish and Portuguese. The COVID-19 infection data was extracted from the Our World in Data website, from January 25, 2020, to July 30, 2020. Results: Among the measures adopted by the country to face the pandemic, the early diagnosis and response to infection, contact tracing, early diagnosis and availability of intensive care for critically ill patients, and encouraging behavioral distancing measures stand out. Among the countries analyzed, Japan has the lowest rates of contamination and mortality in absolute terms by COVID-19. Conclusions: social distancing measures, early diagnosis, and treatment seem to have contributed to the success in combating COVID-19 in Japan. In the studied period, in a million inhabitants, Japan had 6.13 cases of covid while Brazil had 218.26 cases. As for the number of deaths confirmed by the disease, the first had a rate of 0.23 while the second had 5.16 cases per million inhabitants. Based on the knowledge of these measures, it is possible to seek similar mechanisms when designing health policies to face pandemics in other countries (AU)

O Sistema de Saúde japonês e seus mecanismos de enfrentamento à COVID-19 / The Japanese Health System and its coping mechanisms against COVID-19

RESUMO: Introdução: apesar de ser o país de maior média de idade no mundo, o Japão tem se destacado no combate à pandemia da COVID-19 (do inglês Coronavirus Disease 2019) ao apresentar reduzidas taxas de contaminação pelo vírus e de mortalidade. Objetivo: discutir acerca das estratégias em saúde adotadas pelo Japão diante da pandemia da doença da COVID-19, bem como avaliar os dados sobre contaminação e mortalidade japoneses em comparação com os outros quatro países com maior média de idade do mundo (Itália, Alemanha, Portugal e Espanha) e o Brasil. Metodologia: para avaliação das estratégias em saúde japonesas foi realizada busca nas bases de dados: PubMed, Cochrane e Scielo, utilizando-se combinação dos termos "Japão", "covid", "coronavirus" e "sistemas de saúde", nos idiomas Inglês, Espanhol e Português. Os dados de infecção da COVID-19 foram extraídos do site Our World in Data, correspondendo ao período de 25 de janeiro de 2020 a 30 de julho de 2020. Resultados: dentre as medidas adotadas pelo país no enfrentamento à pandemia, destacam-se o diagnóstico e resposta precoces à infecção, o rastreamento de contatos, o diagnóstico precoce e disponibilidade de cuidados intensivos para pacientes graves e estímulo a medidas comportamentais de distanciamento. Dentre os países analisados, o Japão apresenta as menores taxas de contaminação e mortalidade em termos absolutos pela COVID-19. Conclusões: medidas de distanciamento social, diagnóstico e tratamento precoces parecem ter contribuído para o sucesso no combate à COVID-19 no Japão. No período estudado, em milhão de habitantes, o Japão teve 6,13 casos de Covid, enquanto o Brasil apresentou 218,26 casos. Já no número de mortes confirmadas pela doença, o primeiro teve uma taxa de 0,23 enquanto o segundo de 5,16 casos por milhão de habitantes. É possível, a partir do conhecimento dessas medidas, buscar mecanismos semelhantes ao traçar políticas de saúde no enfrentamento de pandemias em outros países. (AU)

ABSTRAC: Introduction: despite being the country with the highest average age globally, Japan has stood out in the fight against the COVID-19 (Coronavirus Disease 2019) pandemic by presenting low contamination rates by the virus and mortality. Objective: we aim to discuss the health strategies adopted by Japan in the face of the COVID-19 disease pandemic, as well as to evaluate data on Japanese contamination and mortality compared to the other four countries with the highest average age in the world (Italy, Germany, Portugal and Spain) and Brazil. Methodology: the search was carried out to evaluate Japanese health strategies by using the following databases: PubMed, Cochrane, and Scielo using a combination of the terms "Japan", "covid", "coronavirus" and "health systems" in English, Spanish and Portuguese. The COVID-19 infection data was extracted from the Our World in Data website, from January 25, 2020, to July 30, 2020. Results: Among the measures adopted by the country to face the pandemic, the early diagnosis and response to infection, contact tracing, early diagnosis and availability of intensive care for critically ill patients, and encouraging behavioral distancing measures stand out. Among the countries analyzed, Japan has the lowest rates of contamination and mortality in absolute terms by COVID-19. Conclusions: social distancing measures, early diagnosis, and treatment seem to have contributed to the success in combating COVID-19 in Japan. In the studied period, in a million inhabitants, Japan had 6.13 cases of covid while Brazil had 218.26 cases. As for the number of deaths confirmed by the disease, the first had a rate of 0.23 while the second had 5.16 cases per million inhabitants. Based on the knowledge of these measures, it is possible to seek similar mechanisms when designing health policies to face pandemics in other countries.(AU)

Association between hyperuricemia and hypertension: a case-control study.

OBJECTIVE: The aim of this study was to evaluate the association between hyperuricemia and systemic arterial hypertension. METHODS: This was a case-control study where individuals aged >18 years were included, who were divided into hypertensive and non-hypertensive groups, excluding those with incomplete information in medical records or with the chronic kidney disease epidemiology collaboration <60 mL/min/1.73 m³. Systemic arterial hypertension was categorized as a dependent variable, while the independent variables were hyperuricemia (i.e., primary variable), sex, education, the practice of physical activity, alcoholism, smoking, diabetes mellitus, chronic kidney disease, a family history of systemic arterial hypertension, age, isolated hyperlipidemia, and mixed hyperlipidemia. Statistical analysis included the univariate and multivariate data analysis, performed by adjusting the logistic regression models using the software R (R Core Team [2018]). RESULTS: Out of 103 patients evaluated, 75 patients were included in this study. In hypertensive patients, hyperuricemia was more frequent (p=0.029), being present in 18.9% individuals. In the univariate analysis, a statistically significant association was found between hyperuricemia and systemic arterial hypertension (OR 10.9; 95%CI 1.29-1420.0; p=0.023); however, in the multivariate analysis, when adjustment was made for age, the only control variable that persisted in the model, this association ceased to be significant (OR 8.5; 95%CI 0.87-1157.0; p=0.070). CONCLUSIONS: There was no independent association between hyperuricemia and systemic arterial hypertension. The latter was associated with diabetes mellitus, chronic kidney disease, and age.

Association between hyperuricemia and hypertension: a case-control study

SUMMARY OBJECTIVE: The aim of this study was to evaluate the association between hyperuricemia and systemic arterial hypertension. METHODS: This was a case-control study where individuals aged >18 years were included, who were divided into hypertensive and non-hypertensive groups, excluding those with incomplete information in medical records or with the chronic kidney disease epidemiology collaboration <60 mL/min/1.73 m³. Systemic arterial hypertension was categorized as a dependent variable, while the independent variables were hyperuricemia (i.e., primary variable), sex, education, the practice of physical activity, alcoholism, smoking, diabetes mellitus, chronic kidney disease, a family history of systemic arterial hypertension, age, isolated hyperlipidemia, and mixed hyperlipidemia. Statistical analysis included the univariate and multivariate data analysis, performed by adjusting the logistic regression models using the software R (R Core Team [2018]). RESULTS: Out of 103 patients evaluated, 75 patients were included in this study. In hypertensive patients, hyperuricemia was more frequent (p=0.029), being present in 18.9% individuals. In the univariate analysis, a statistically significant association was found between hyperuricemia and systemic arterial hypertension (OR 10.9; 95%CI 1.29-1420.0; p=0.023); however, in the multivariate analysis, when adjustment was made for age, the only control variable that persisted in the model, this association ceased to be significant (OR 8.5; 95%CI 0.87-1157.0; p=0.070). CONCLUSIONS: There was no independent association between hyperuricemia and systemic arterial hypertension. The latter was associated with diabetes mellitus, chronic kidney disease, and age.

Antifungal Efficacy of Amphotericin B in Candida Albicans Endocarditis Therapy: Systematic Review.

INTRODUCTION: Although it is the most common agent among the fungal causes of endocarditis, Candida albicans endocarditis is rare. OBJECTIVE: To evaluate the efficacy of amphotericin B in the treatment of C. albicans endocarditis beyond a systematic review. DATA SEARCH: Articles in English, Spanish and Portuguese, conducted in the following databases: MEDLINE, LILACS, IBECS and SciELO, in humans and published in the last 25 years. STUDY SELECTION: Observational studies, clinical trials, and case series providing data on the amphotericin B use in patients with a C. albicans endocarditis diagnosis without age limitations. DATA SYNTHESIS: From the initial search (n=79), 25 articles were fully evaluated, of which 19 were excluded for meeting one or more exclusion criteria, remaining five articles (two observational studies and three case series). Patients using amphotericin B demonstrated improvement in survival rates, and its main use was in association with the surgical method as well as with caspofungin association. CONCLUSION: Literature lacks evidence to conclude about efficacy and safety of amphotericin B in the treatment of fungal endocarditis. Randomized clinical trials are necessary to provide better evidence on the subject.

Antifungal efficacy of amphotericin b in candida albicans endocarditis therapy: systematic review

Abstract Introduction: Although it is the most common agent among the fungal causes of endocarditis, Candida albicans endocarditis is rare. Objective: To evaluate the efficacy of amphotericin B in the treatment of C. albicans endocarditis beyond a systematic review. Data search: Articles in English, Spanish and Portuguese, conducted in the following databases: MEDLINE, LILACS, IBECS and SciELO, in humans and published in the last 25 years. Study selection: Observational studies, clinical trials, and case series providing data on the amphotericin B use in patients with a C. albicans endocarditis diagnosis without age limitations. Data synthesis: From the initial search (n=79), 25 articles were fully evaluated, of which 19 were excluded for meeting one or more exclusion criteria, remaining five articles (two observational studies and three case series). Patients using amphotericin B demonstrated improvement in survival rates, and its main use was in association with the surgical method as well as with caspofungin association. Conclusion: Literature lacks evidence to conclude about efficacy and safety of amphotericin B in the treatment of fungal endocarditis. Randomized clinical trials are necessary to provide better evidence on the subject.

Tacrolimus therapeutic efficacy in post-liver transplant patients with Cytochrome P450 3A5 (CYP3A5) genetic polymorphisms. / Eficácia terapêutica do Tacrolimo em pacientes pós-transplante hepático com polimorfismos genéticos do citocromo P450 3A5 (CYP3A5).

Genetic polymorphisms of CYP3A5 have been pointed out as factors that influenciates tacrolimus immunosuppressive efficacy in post liver transplant patients. This study aims to review the literature on the influence of cytochrome P450 3A5 (CYP3A5) genetic polymorphisms of tacrolimus in post-liver transplant patients. This study is a literature review. A combination of the descriptors "tacrolimus", "liver transplant", "cytochrome P-450 CYP3A inhibitors" and "genetic polymorphism" were used in the databases PubMed, Cochrane Library, Scopus and Scielo, being evaluated only studies between 2009 and 2019 in English, Portuguese or Spanish. A total of six studies, each from a different population were summarized. Initially, the pharmacological aspects of tacrolimus were discussed, including details on its pharmacodynamics, pharmacokinetics and toxicity After that, we analyzed the studies that correlates CYP3A5 genetic polymorphisms and tacrolimus efficacy, including the ethnical specifications and the general limittions of the studies. The CYP3A5 polymorphisms have pointed to alterations in the metabolism of tacrolimus according to the ethnic and populational genotype, specially the *1 and *3*3 alleles, reflecting in the need for dose adjustment and also in post liver transplant rejection.

Os polimorfismos genéticos do CYP3A5 têm sido apontados enquanto fatores influenciadores na eficácia farmacológica com tacrolimo em pacientes em terapia imunossupressora no pós-transplante hepático. O presente estudo objetiva realizar uma revisão da literatura acerca da influência dos polimorfismos genéticos do citocromo P450 3A5 (CYP3A5) na eficácia terapêutica com tacrolimo em indivíduos pós-transplante hepático. Revisão da literatura. Foi utilizada a combinação dos descritores "tacrolimo", "transplante de fígado", "inibidores do citocromo P-450 CYP3A" e "polimorfismo genético", nas bases de dados: PubMed, The Cochrane Library, Scopus e Scielo, sendo avaliados apenas estudos publicados entre 2009 e 2019 em inglês, português ou espanhol. Ao todo foi feita a sumarização de seis estudos, cada um avaliando uma diferente população. Inicialmente, foram abordados os aspectos farmacológicos do tacrolimo, incluindo detalhes sobre sua farmacodinâmica, farmacocinética e toxicidade. Na seção seguinte, foi realizada a avaliação de estudos que tratam da relação entre os polimorfismos genéticos do CYP3A5 e a eficácia farmacológica com o tacrolimo, incluindo as especificações étnicas e as limitações gerais dos estudos. Os polimorfismos genéticos do CYP3A5 têm apontado para alterações no metabolismo do tacrolimo de acordo com um recorte étnico e populacional, com destaque para os alelos *1 e *3*3, refletindo na necessidade de ajuste de dose ou até mesmo nas taxas de rejeição do órgão.

Relato de experiência de grupo de pesquisa em epidemiologia e cardiologia / Experience report from an epidemiology and cardiology research group

RESUMO: A formação de grupos acadêmicos durante o curso de medicina é importante para a construção e compartilhamento de conhecimentos e habilidades fundamentais para a prática médica. O presente trabalho relata a experiência de um ano de atividades (2017-2018) de um grupo de pesquisa em epidemiologia e cardiologia. Apresentamos os principais pontos de motivação, objetivos e funcionamento do grupo, no intuito de fornecer um modelo estrutural que possa servir de inspiração e debate para a formação de outros grupos de pesquisa constituídos por estudantes de medicina ao redor do país. Ao longo de um ano foram apresentados em eventos científicos os resultados das pesquisas do grupo, além da publicação de artigos em periódicos científicos na área da saúde, totalizando 12 trabalhos acadêmicos. Como meio de fornecer uma ferramenta de avaliação quantitativa de análise das atividades do grupo, foram apresentados os resultados da autoavaliação desenvolvida pelos membros acadêmicos após um ano de atividades. Considerando o elevado número de publicações biomédicas e o aumento na exigência de conhecimentos em pesquisa e medicina baseada em evidências nos últimos anos, a formação de grupos de pesquisa apresenta-se como uma alternativa para complementação de conhecimentos teóricos e práticos para a formação médica, permitindo aos futuros profissionais uma visão crítica da produção do conhecimento científico, uma prática médica baseada em evidências, um melhor enfretamento das exigências de mercado e dos interesses econômicos na área de saúde. (AU)

ABSTRACT: The establishment of academic groups during medical school is important for the construction and sharing of knowledge and fundamental skills to good medical practice. This paper reports a one-year experience of activities (2017-2018) of a research group in epidemiology and cardiology. The presentation of the motivation reasons, objectives, and performance of the group to provide a structural model that could serve as inspiration and debate for the establishment of other research groups made up from and for medical students from all over the world. During one year of activity, the findings of the group research were presented in scientific events, as well as the publication of articles in scientific journals in field of health sciences, totaling 12 academic papers. As a means of providing a quantitative evaluation tool for the analysis of the group's activities, the results of the self-assessment developed by the academic members after one year of activities were presented. Considering the high number of biomedical publications and the increase in the demand for knowledge in research and evidence-based medicine in recent years, the establishment of research groups is an alternative to complement theoretical and practical knowledge for medical education, allowing to future professionals a critical view of the production of scientific knowledge, evidence-based medical practice, a better understanding of market demands, and economic interests in health. (AU)

Eficácia terapêutica do Tacrolimo em pacientes pós-transplante hepático com polimorfismos genéticos do citocromo P450 3A5 (CYP3A5) / Tacrolimus therapeutic efficacy in post-liver transplant patients with Cytochrome P450 3A5 (CYP3A5) genetic polymorphisms

RESUMO Os polimorfismos genéticos do CYP3A5 têm sido apontados enquanto fatores influenciadores na eficácia farmacológica com tacrolimo em pacientes em terapia imunossupressora no pós-transplante hepático. O presente estudo objetiva realizar uma revisão da literatura acerca da influência dos polimorfismos genéticos do citocromo P450 3A5 (CYP3A5) na eficácia terapêutica com tacrolimo em indivíduos pós-transplante hepático. Revisão da literatura. Foi utilizada a combinação dos descritores "tacrolimo", "transplante de fígado", "inibidores do citocromo P-450 CYP3A" e "polimorfismo genético", nas bases de dados: PubMed, The Cochrane Library, Scopus e Scielo, sendo avaliados apenas estudos publicados entre 2009 e 2019 em inglês, português ou espanhol. Ao todo foi feita a sumarização de seis estudos, cada um avaliando uma diferente população. Inicialmente, foram abordados os aspectos farmacológicos do tacrolimo, incluindo detalhes sobre sua farmacodinâmica, farmacocinética e toxicidade. Na seção seguinte, foi realizada a avaliação de estudos que tratam da relação entre os polimorfismos genéticos do CYP3A5 e a eficácia farmacológica com o tacrolimo, incluindo as especificações étnicas e as limitações gerais dos estudos. Os polimorfismos genéticos do CYP3A5 têm apontado para alterações no metabolismo do tacrolimo de acordo com um recorte étnico e populacional, com destaque para os alelos *1 e *3*3, refletindo na necessidade de ajuste de dose ou até mesmo nas taxas de rejeição do órgão.

ABSTRACT Genetic polymorphisms of CYP3A5 have been pointed out as factors that influenciates tacrolimus immunosuppressive efficacy in post liver transplant patients. This study aims to review the literature on the influence of cytochrome P450 3A5 (CYP3A5) genetic polymorphisms of tacrolimus in post-liver transplant patients. This study is a literature review. A combination of the descriptors "tacrolimus", "liver transplant", "cytochrome P-450 CYP3A inhibitors" and "genetic polymorphism" were used in the databases PubMed, Cochrane Library, Scopus and Scielo, being evaluated only studies between 2009 and 2019 in English, Portuguese or Spanish. A total of six studies, each from a different population were summarized. Initially, the pharmacological aspects of tacrolimus were discussed, including details on its pharmacodynamics, pharmacokinetics and toxicity After that, we analyzed the studies that correlates CYP3A5 genetic polymorphisms and tacrolimus efficacy, including the ethnical specifications and the general limittions of the studies. The CYP3A5 polymorphisms have pointed to alterations in the metabolism of tacrolimus according to the ethnic and populational genotype, specially the *1 and *3*3 alleles, reflecting in the need for dose adjustment and also in post liver transplant rejection.

Prevalence of depression and anxiety and their association with cardiovascular risk factors in Northeast Brasil primary care patients.

BACKGROUND: Depression and anxiety disorders (DAD) are the most prevalent mental health conditions worldwide. Among the adult population served in basic care, it is estimated that depression affects about 14.3% of these individuals worldwide, and between 21.4% and 31% in Brasil. Anxiety affects up to 33.7% of the population during their lifetimes. OBJECTIVES: estimate the prevalence proportions of DAD among patients in a municipality in Northeast Brasil and study the association between DAD and cardiovascular risk factors. METHODS: a cross-sectional study with the medical records of patients from primary care centers in Jaboatão dos Guararapes, Pernambuco. Patients aged ≥ 18 years and regularly followed-up were included. Exclusion criteria: a history of traumatic brain injury, alcohol or drug abuse, previous stroke, medical conditions or medications that mimic DAD symptoms. Subjects were divided into two groups depending on the presence or absence of DAD, and cardiovascular risk factors were compared between groups. RESULTS: A total of 1030 subjects were initially included, of whom 215 (20%) were excluded. No-DAD subjects had more history of myocardial infarction and alcoholism. The prevalence of depression was 10.3%, anxiety disorder was 27.1%, and mixed DAD represented 4.5%. There was a significant association between DAD and hypertension (OR = 2.11; 95%CI: 1.16 -3.84; p=0.01), obesity (OR = 4.47; 95%CI: 1.74 -11.46; p=0.002), and hyperlipidemia (OR = 3.88; 95%CI: 1.81-8.3; p<0.001). CONCLUSION: DAD were associated with an increased risk for arterial hypertension, obesity, and hyperlipidemia.

Prevalence of depression and anxiety and their association with cardiovascular risk factors in Northeast Brasil primary care patients

SUMMARY BACKGROUND: Depression and anxiety disorders (DAD) are the most prevalent mental health conditions worldwide. Among the adult population served in basic care, it is estimated that depression affects about 14.3% of these individuals worldwide, and between 21.4% and 31% in Brasil. Anxiety affects up to 33.7% of the population during their lifetimes. OBJECTIVES: estimate the prevalence proportions of DAD among patients in a municipality in Northeast Brasil and study the association between DAD and cardiovascular risk factors. METHODS: a cross-sectional study with the medical records of patients from primary care centers in Jaboatão dos Guararapes, Pernambuco. Patients aged ≥ 18 years and regularly followed-up were included. Exclusion criteria: a history of traumatic brain injury, alcohol or drug abuse, previous stroke, medical conditions or medications that mimic DAD symptoms. Subjects were divided into two groups depending on the presence or absence of DAD, and cardiovascular risk factors were compared between groups. RESULTS: A total of 1030 subjects were initially included, of whom 215 (20%) were excluded. No-DAD subjects had more history of myocardial infarction and alcoholism. The prevalence of depression was 10.3%, anxiety disorder was 27.1%, and mixed DAD represented 4.5%. There was a significant association between DAD and hypertension (OR = 2.11; 95%CI: 1.16 -3.84; p=0.01), obesity (OR = 4.47; 95%CI: 1.74 -11.46; p=0.002), and hyperlipidemia (OR = 3.88; 95%CI: 1.81-8.3; p<0.001). CONCLUSION: DAD were associated with an increased risk for arterial hypertension, obesity, and hyperlipidemia.

RESUMO INTRODUÇÃO: Transtornos de ansiedade e depressão (TAD) são os distúrbios psiquiátricos mais comuns no mundo. Dentre a população adulta atendida na atenção básica, estima-se que a depressão afete cerca de 14,3% desses indivíduos mundialmente, podendo este valor ir de 21,4% a 31% no Brasil. A ansiedade afeta até 33,7% da população durante sua vida. OBJETIVO: Estimar a prevalência de TAD em pacientes da atenção primária em um município do Nordeste brasileiro e associar sua ocorrência com fatores de risco cardiovasculares. MÉTODOS: Um estudo de coorte transversal com análise de prontuário de pacientes atendidos em unidades de saúde da família de Jaboatão dos Guararapes, Pernambuco. Foram incluídos pacientes ≥18 anos e acompanhados regularmente. Critérios de exclusão: história de trauma crânio encefálico, abuso de álcool e drogas, acidente vascular cerebral prévio, doenças ou medicações que mimetizem sintomas de TAD. Os indivíduos foram divididos em dois grupos, a depender da presença ou não de TAD, e os fatores de risco cardiovascular foram comparados entre os grupos. RESULTADOS: De um total de 1.030 indivíduos recrutados, 215 (20%) foram excluídos. O grupo não TAD apresentou mais história de infarto do miocárdio e etilismo. A prevalência de depressão foi de 10,3%, a de ansiedade foi de 27,1% e a associação entre os dois foi de 4,5%. Houve associação significativa entre TAD e hipertensão (OR = 2,11; IC95: 1,16-3,84; p=0,01), obesidade (OR = 4,47; IC95%: 1,74-11,46; p=0,002) e dislipidemia (OR = 3,88; IC95%: 1,81-8,3; p<0,001). CONCLUSÃO: TAD estão associados com maior risco de hipertensão arterial, obesidade e dislipidemia.

Efeitos dos picnogenol® na doença aterosclerótica crônica / Effects of picnogenol® on chronic atherosclerosis

A doença aterosclerótica crônica (DAC) é uma condição bastante prevalente em nosso meio e uma das principais doenças cardiovasculares ligadas ao envelhecimento. Dentre as opções terapêuticas adjuvantes, o Picnogenol ®, extrato da casca do Pinus pinaster, tem sido alvo de estudo em decorrência de função antioxidante, anti-inflamatória e antiplaquetária. Este artigo é uma revisão narrativa, cujo objetivo é avaliar o uso do Picnogenol® como opção terapêutica da DAC. Os estudos incluídos foram pesquisados nas bases de dados: PubMed, Scielo, The Cochrane Library, Scopus e LILACS, sendo excluídos, considerando suas restrições para avaliação terapêutica, os relatos de caso e séries de caso com n ≤ 5. Como resultado, os estudos têm apontado vantagens do uso Picnogenol® no tratamento da DAC, assim como de outras doenças cardiovasculares, porém, o número de pesquisas ainda é pequeno (principalmente ensaios clínicos) e há importantes limitações de tamanho amostral, o que dificulta sua atual recomendação na prática clínica

Chronic atherosclerosis is a highly prevalent condition and one of the main cardiovascular diseases linked to the aging process. Among the adjuvant therapeutic options, Pycnogenol® (Pinus pinaster bark extract) has been studied because of its antioxidant, anti-inflammatory and antiplatelet functions. This article is a narrative review aimed at evaluating the use of Pycnogenol® as a therapeutic option in the treatment of chronic atherosclerosis. The studies included were obtained from the following databases: PubMed, Scielo, The Cochrane Library, Scopus and LILACS. Case reports and case series with n≤5 were excluded due to their restrictions for therapeutic evaluation. As a result, the studies have indicated advantages in the use of Pycnogenol® in the treatment of chronic atherosclerosis as well as other cardiovascular diseases. However, the number of studies is still small (particularly clinical trials), and there are important sample size limitations, which restricts its current recommendation in clinical practice

Fase acelerada da síndrome de Chediak-Higashi: revisão de literatura / Accelerated phase of Chediak-Higashi syndrome: review of literature

Indivíduos afetados pela síndrome de Chediak-Higashi se apresentam clinicamente com diversas alterações orgânicas, a partir de mutações que afetam a função fagocitária e do gene regulador do tráfego lisossomal. A forma acelerada da síndrome cursa com uma série de alterações hematológicas e sistêmicas, sendo grave e usualmente incorrendo em morte precoce. O objetivo do artigo foi realizar uma pesquisa na literatura acerca da fase acelerada da síndrome de Chediak-Higashi. Foi realizada a busca nas bases de dados: PubMed, The Cochrane Library e SciELO, por estudos em humanos publicados em inglês, espanhol ou português nos últimos 15 anos. Devido a seu nível de gravidade, a síndrome de Chediak-Higashi demonstra a importância de seu conhecimento pelos profissionais médicos a fim de reduzir o número de subdiagnósticos, consequentemente diminuindo as taxas de mortalidade e promovendo melhora na qualidade de vida de seus portadores.

Individuals affected by Chediak-Higashi syndrome present themselves clinically with several organic alterations, from mutations that affect the phagocytic and the functions of the lysosomal traffic regulator gene. The accelerated form of the syndrome presents with a series of hematological and systemic alterations, being serious and usually incurring in early death. The objective of this paper was to develop a literature review about the accelerated phase of Chediak-Higashi syndrome. The source was developed at the following databases: PubMed, The Cochrane Library, and SciELO, being included human studies published in English, Spanish or Portuguese in the last 15 years. Due to its severity, Chediak-Higashi syndrome demonstrates the importance of its knowledge by medical professionals in order to reduce the number of underdiagnostics, consequently reducing mortality rates and promoting improvement in the quality of life of the patients.

Impacts of Cytochrome P450 2D6 (CYP2D6) Genetic Polymorphism in Tamoxifen Therapy for Breast Cancer.

Tamoxifen (TMX) is the main drug used both in pre and postmenopausal women as adjuvant treatment for hormone receptor-positive breast cancer. An important barrier to the use of TMX is the development of drug resistance caused by molecular processes related to genetic and epigenetic mechanisms, such as the actions of cytochrome P450 2D6 (CYP2D6) polymorphisms and of its metabolites. The present study aimed to review recent findings related to the impact of CYP2D6 polymorphisms and how they can affect the results of TMX in breast cancer treatment. The keywords CYP2D6, tamoxifen, and breast cancer were searched in the PubMed, Scopus, The Cochrane Library, Scielo, and Bireme databases. Studies related to other types of neoplasms or based on other isoenzymes from cytochrome P450, but not on CYP2D6, were excluded. The impact of CYP2D6 polymorphisms in the TMX resistance mechanism remains unclear. The CYP2D6 gene seems to contribute to decreasing the efficacy of TMX, while the main mechanism responsible for therapy failure, morbidity, and mortality is the progression of the disease.

O tamoxifeno é a principal droga que pode ser utilizada como tratamento hormonal adjuvante em pacientes portadoras de câncer de mama receptor hormonal positivo tanto na pré- quanto na pós-menopausa. Uma das maiores barreiras em seu uso é o desenvolvimento de resistência medicamentosa causada por meio de processos moleculares relacionados a mecanismos genéticos e epigenéticos, como a ação dos polimorfismos do gene citocromo P450 2D6 (CYP2D6) e seus metabólitos. O presente estudo busca revisar as descobertas recentes acerca dos impactos dos polimorfismos do gene CYP2D6 e de como eles podem afetar os resultados do tamoxifeno na terapêutica do câncer de mama. As palavras-chave CYP2D6, tamoxifeno e câncer de mama foram buscadas nas bases de dados Pubmed, Scopus, The Cochrane Library, Scielo e Bireme. Estudos relacionados com outros tipos de câncer ou relacionados a outras isoenzimas do citocromo P450 que não o CYP2D6 foram excluídos. O impacto do polimorfismo do CYP2D6 nos mecanismos de resistência ao tamoxifeno permanecem controversos. O gene CYP2D6 parece reduzir a eficácia do TMX; entretanto, os principais fatores associados a falha terapêutica são morbimortalidade e a progressão da doença.