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.

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.

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.

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.

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.

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: O transtorno depressivo maior (TDM) é uma doença mental incapacitante caracterizada por episódios de pelo menos 2 semanas de mudanças claras no afeto, cognição e funções neurovegetativas. Vários estudos de neuroimagem, realizados através de imagem de ressonância magnética (IRM), examinaram mudanças morfométricas em pacientes com TDM, com resultados não conclusivos. Este estudo tem como objetivo revisar a literatura e realizar uma metanálise sobre o volume do hipocampo (VHc) em pacientes com TDM. Métodos: Estudos de VHc em pacientes com TDM foram identificados a partir dos principais bancos de dados (MEDLINE, EMBASE, The Cochrane Library, Scopus, PsycINFO e SciELO) usando os seguintes termos: depression, major depressive disorder, MDD, unipolar, magnetic resonance imaging, MRI e hippocampus. Resultados: Foi realizada uma metanálise de 29 estudos que preencheram os critérios específicos. A amostra foi composta por 1327 pacientes e 1004 indivíduos saudáveis. Os estudos foram altamente heterogêneos em relação a idade, gênero, idade do primeiro episódio e duração média da doença, mas o efeito combinado da depressão foi significativo em ambos os hipocampos. O TDM foi associado à atrofia do hipocampo à direita [-0,43; intervalo de confiança de 95% (IC95%) −0,66 a −0,21] e à esquerda (-0,40; IC95% −0,66 a −0,15). Conclusões: O TDM parece estar associado à atrofia global do VHc. Estudos longitudinais com maior tempo de seguimento, projetados para analisar a influência dos fatores sociodemográficos nessa relação, são necessários para obter evidências mais robustas.

Abstract Introduction: Major depressive disorder (MDD), an incapacitating mental disorder, is characterized by episodes of at least 2 weeks of apparent changes in mood, cognition, and neurovegetative functions. Many neuroimaging studies using magnetic resonance imaging (MRI) have examined morphometric changes in patients with MDD, but the results are not conclusive. This study aims to review the literature and perform a meta-analysis on hippocampal volume (HcV) in patients with MDD. Methods: Studies on HcV in patients with MDD diagnosis were identified from major databases (MEDLINE, EMBASE, The Cochrane Library, Scopus, PsycINFO, and SciELO) using the search terms depression, major depressive disorder, MDD, unipolar, magnetic resonance imaging, MRI, and hippocampus. Results: A meta-analysis of 29 studies fulfilling specific criteria was performed. The sample included 1327 patients and 1004 healthy participants. The studies were highly heterogeneous with respect to age, sex, age of onset, and average illness duration. However, the pooled effect size of depression was significant in both hippocampi. MDD was associated with right (-0.43; 95% confidence interval [95%CI] −0.66 to −0.21) and left (-0.40; 95%CI −0.66 to −0.15) hippocampal atrophy. Conclusions: MDD seems to be associated with global HcV atrophy. Larger longitudinal follow-up studies designed to analyze the influence of sociodemographic variables on this relationship are required to yield better evidence about this topic.

Resumo Otamoxifeno é a principal drogaque pode ser utilizada comotratamentohormonal adjuvante empacientesportadoras de câncer demamareceptor hormonal positivotanto na pré- quanto na pós-menopausa.Umadasmaiores barreirasemseu 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.Opresente 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

Abstract 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 TMXis the development ofdrug resistance causedby 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.

RESUMO Demência é uma terminologia geral para um grupo heterogêneo de doenças orgânicas e neurodegenerativas. As causas cerebrovasculares são responsáveis por 20% dos casos. Objetivo: Descrever as características clínicas e epidemiológicas de indivíduos maiores de 60 anos diagnosticados com demência vascular ou mista em hospital de referência em demência. Métodos: Estudo retrospectivo descritivo de 2014 a 2017 em idosos com demência. Outras formas de demência ou uso de medicamentos que mimetizem distúrbios cognitivos foram excluídos. O inventário neuropsiquiátrico de 12 itens foi usado para avaliar os sintomas neuropsiquiátricos (SNP). Resultados: 81.1% dos pacientes apresentaram SNP, apenas 15% tiveram dois ou mais. Apatia foi o mais frequente (56,6%). Houve associação entre CDR 1 ou 2 e SNP (OR = 6.16, 95% CI: 1.36-27.9, p = 0.02). Conclusão: Geralmente há um sintoma isolado, sendo apatia o principal. Encontramos associação entre demência leve e moderada e SNP.

ABSTRACT Dementia is a general term for a heterogeneous group of organic neurodegenerative diseases. Cerebrovascular causes account for 20% of cases. Objective: To describe the clinical and epidemiological features of individuals aged >60 years diagnosed with vascular dementia (VD) or mixed dementia (MxD) in a referral hospital for dementia. Methods: A descriptive, retrospective study was carried out from 2014 to 2017 involving elderly individuals (≥60 years) with VA or MxD. Patients presenting other forms of dementia or in use of medication that mimics cognitive disorders were excluded. The 12-item Neuropsychiatric Inventory was used to assess neuropsychiatric symptoms (NPS). Results: 81.1% of the patients presented NPS and only 15% had two or more symptoms. Apathy was the most frequent NPS (56.6%). There was an association between CDR score 1 or 2 and NPS (OR = 6.16, 95% CI: 1.36-27.9, p = 0.02). Conclusion: Most patients had a single symptom, predominantly apathy. There was an association between mild-to-moderate dementia and NPS.

RESUMO JUSTIFICATIVA E OBJETIVOS: Polineuropatia periférica e síndrome do túnel do carpo são doenças debilitantes, associadas ao diabetes mellitus em cerca de 12 a 21% dos casos. Inexistem evidências significativas que direcionem sobre a diferenciação clinica entre essas síndromes dolorosas e o tratamento específico. O objetivo deste estudo foi relatar o quadro clínico de um paciente que apresentou polineuropatia periférica associada à síndrome do túnel do carpo, focando nas medidas terapêuticas e discutindo acerca da diferenciação clínica entre as doenças referidas. RELATO DO CASO: Paciente do gênero masculino, 68 anos, casado, aposentado buscou atendimento médico por queixa de dor queimante, sobretudo em membro superior esquerdo. Refere dor também em membros inferiores, com exacerbação noturna, além de dormência nas extremidades, intensidade de 6 na escala visual analógica. Presença de ponto-gatilho nos músculos trapézio e elevador da escápula. Passou por cirurgia de liberação por diagnóstico de síndrome túnel do carpo há 2 anos, sem melhora pós-cirúrgica. Tem histórico de hipertensão arterial, diabetes mellitus tipo 2 e hanseníase. No exame físico: presença de hipoestesia dolorosa em bota e luva e possível déficit motor em C6 e C7. Eletromiografia evidencia polineuropatia periférica mista de membros inferiores e síndrome do túnel do carpo mediana à esquerda. Houve melhora na amplitude de movimento nos miótomos C6 e C7. A dor foi para 3 na escala visual analógica após 2 semanas sob uso de gabapentina e duloxetina. CONCLUSÃO: É difícil a diferenciação clínica entre neuropatia de outra etiologia e polineuropatia periférica. O tratamento proposto trouxe uma melhora na VAS de 50% após duas semanas. A infusão de lidocaína a 5% representou melhora aguda na dor referida pelo paciente.

ABSTRACT BACKGROUND AND OBJECTIVES: Peripheral neuropathy and carpal tunnel syndrome are debilitating diseases associated to diabetes mellitus in 12 to 21% of cases. There are no significant evidences of the clinical differentiation between such painful syndromes and their specific management. This study aimed at reporting the clinical presentation of a patient with peripheral polyneuropathy associated to carpal tunnel syndrome, focusing on therapeuthic approaches and discussing clinical differentiation between both diseases. CASE REPORT: Male patient, 68 years old, married, retired, who looked for medical assistance complaining of burning pain, especially in left upper limb. He also referred pain in lower limbs with night exacerbation, in addition to numbness in extremities and pain intensity of 6 in the visual analog scale. Presence of trigger- points in trapezius and levator scapulae muscles. Patient was submitted to decompression surgery due to carpal tunnel syndrome diagnosis two years ago, however without postoperative improvement. Patient refers pain in upper and lower limbs, with nocturnal exacerbation, numbness and pain in extremities. He has history of hypertension, diabetes mellitus type 2 and leprosy. At physical evaluation: painful boot and glove hypoesthesia and possible motor deficit in C6 and C7. Electromyography showed mixed peripheral polyneuropathy of lower limbs and median carpal syndrome to the left. There has been movement amplitude improvement in myotomes C6 and C7. Pain decreased to 3 in the visual analog scale after two weeks under gabapentin and duloxetine. CONCLUSION: It is difficult to clinically differentiate between neuropathy of different etiology and peripheral polyneuropathy. The proposed treatment has provided 50% improvement in the visual analog scale two weeks later. Lidocaine infusion at 5% has provided acute improvement of patient’s pain.