Abstract Introduction: Cardiovascular disease is an important cause of death among patients with chronic kidney disease (CKD). Valve calcification is a predictor of cardiovascular mortality and coronary artery disease. Objective: To assess heart valve disease frequency, associated factors, and progression in CKD patients. Methods: We conducted a retrospective study on 291 CKD patients at Hospital das Clínicas de Pernambuco. Inclusion criteria were age ≥ 18 with CKD and valve disease, while those on conservative management or with missing data were excluded. Clinical and laboratory variables were compared, and patients were categorized by dialysis duration (<5 years; 5–10 years; >10 years). Statistical tests, including chi-square, Fisher’s exact, ANOVA, and Kruskal-Wallis, were employed as needed. Simple and multivariate binary regression models were used to analyze valve disease associations with dialysis duration. Significance was defined as p < 0.05. Results: Mitral valve disease was present in 82.5% (240) of patients, followed by aortic valve disease (65.6%; 86). Over time, 106 (36.4%) patients developed valve disease. No significant association was found between aortic, pulmonary, mitral, or tricuspid valve disease and dialysis duration. Secondary hyperparathyroidism was the sole statistically significant factor for mitral valve disease in the regression model (OR 2.59 [95% CI: 1.09–6.18]; p = 0.031). Conclusion: CKD patients on renal replacement therapy exhibit a high frequency of valve disease, particularly mitral and aortic valve disease. However, no link was established between dialysis duration and valve disease occurrence or progression.

Resumo Introdução: Doenças cardiovasculares são uma causa significativa de morte em pacientes com Doença Renal Crônica (DRC). A calcificação valvar é preditor de mortalidade cardiovascular e doença arterial coronariana. Objetivo: Avaliar a frequência, fatores associados e progressão de valvopatias em pacientes com DRC. Métodos: Coorte retrospectiva com 291 pacientes ambulatoriais no Hospital das Clínicas de Pernambuco. Inclusão: ≥18 anos com DRC e valvopatia; exclusão: tratamento conservador ou dados incompletos. Variáveis clínicas e laboratoriais foram comparadas e categorizadas por tempo de terapia dialítica (TTD): <5 anos, 5–10 anos, >10 anos. Foram aplicados os testes Qui-quadrado, exato de Fisher, ANOVA, Kruskal-Wallis. Associação entre valvopatia e TTD foi avaliada por regressão binária. Significância foi definida como p < 0,05. Resultados: A valvopatia mitral foi encontrada em 82,5% (240) dos casos, seguida da aórtica (65,6%; 86). Houve progressão da doença valvar em 106 (36,4%) pacientes. Não houve associação entre valvopatias aórtica, pulmonar, mitral ou tricúspide e TTD. Hiperparatireoidismo secundário foi a única variável explicativa significativa na regressão para valvopatia mitral (OR 2,59 [IC95%: 1,09–6,18]; p = 0,031). Conclusão: Encontramos alta frequência de valvopatias, especialmente mitral e aórtica, aem pacientes com DRC. Não houve associação entre TTD e valvopatia.

Abstract: Introduction: The occurrence of pandemics, such as Covid-19, leads to a psychosocial disturbance that can break the limits of the population’s coping capacity, generating tensions and anxieties that are expressed in various degrees among those involved. Objective: To analyze the repercussions of the COVID-19 pandemic on the mental health of medical students in the State of Pernambuco. Methods: Cross-sectional analytical study conducted between July and August 2021 with medical students from 11 universities in Pernambuco. The dependent variables analyzed were the scores of anxiety, depression; the independent variables were resilience score, socio-demographic, behavioral characteristics and health conditions. The data were collected through Google Forms. Beck’s Anxiety and Depression Inventories, and Wagnild and Young’s Resilience Scale were applied. The study was approved by the local ethics committee and informed consent was sought and given. The data were analyzed using SPSS 25, considering as significant a p-value < 0,05. Result: 416 participants were included, the majority (60.9%) of the students were women, the average age was 25 years, and 73.8% of them lived in the municipality of their university. Moderate and severe anxiety symptoms were found in 27.2% and 10.3% of the sample, respectively. Moderate depressive symptoms were observed in 17.8% of the students. About 25% of the sample reported a low or very low degree of resilience. High resilience (Odds Ratio [OR] 0.18 [0.08-0.41]; p <0.001) and psychological support prior to the pandemic (OR 0.36 [0.14-0.95]; p = 0 .04) were protective factors and attending the clinical cycle (2nd-3rd year) was an independent risk factor (OR 1.95 [1.07-3.55]; p = 0.02) for moderate to severe anxiety. High resilience (OR 0.01 [0.02-0.11]; p < 0.001 and returning to one’s hometown during the suspension of classes (OR 0.41 [0.18-0.91]; p = 0.02) were protective factors and attending the clinical cycle was an independent risk factor (OR 2.74 [1.26-5.93]; p = 0.01) for moderate to severe depression. Conclusion: We found a high prevalence of moderate and severe anxiety symptoms, as well as moderate depressive symptoms. A high proportion of students demonstrated a low or very low degree of resilience.

Resumo: Introdução: As pandemias, como a de Covid-19, resultam em perturbação psicossocial que pode romper os limites da capacidade de enfrentamento, de modo a gerar tensões e angústias que se expressam variavelmente entre os envolvidos. Objetivo: analisar as repercussões da pandemia de Covid-19 na saúde mental de estudantes de Medicina do estado de Pernambuco. Método: estudo transversal e descritivo-analítico realizado entre julho e agosto de 2021 com estudantes de Medicina das 11 faculdades de Pernambuco. Como variáveis dependentes, foram analisados os escores de ansiedade e depressão. Quanto às variáveis independentes, foram estudadas: escore de resiliência, características sociodemográficas e comportamentais, e condições de saúde. A coleta dos dados foi realizada por meio da plataforma Google Forms. Aplicaram-se o Inventário de Beck para ansiedade e depressão e a escala de resiliência de Wagnild e Young. O estudo foi aprovado pelo Comitê de Ética em Pesquisa do Centro Universitário Maurício de Nassau, e os participantes concordaram o Termo de Consentimento Livre e Esclarecido. Os dados foram analisados pelo programa SPSS 25, considerando significativo valor p < 0,05. Resultado: participaram da pesquisa 416 estudantes. A amostra foi composta predominantemente por mulheres (60,9%), com idade média de 25 anos, das quais 73,8% tinham residência fixa no município da faculdade. Sintomas de ansiedade moderada e grave foram verificados em 27,2% e 10,3% dos avaliados, respectivamente. Observaram-se sintomas depressivos moderados em 17,8% dos estudantes. Cerca de 25% da amostra apresentou grau de resiliência baixo ou muito baixo. Resiliência alta (razão de chances [RC] = 0,18 [0,08-0,41]; p < 0,001) e suporte psicológico anterior à pandemia (RC = 0,36 [0,14-0,95]; p = 0,04) foram fatores de proteção; e cursar o ciclo clínico (quinto-oitavo períodos) foi fator de risco independente (RC = 1,95 [1,07-3,55]; p = 0,02) para ansiedade de moderada a grave. Resiliência alta (RC = 0,01 [0,02-0,11]; p < 0,001 e retornar à cidade natal durante a suspensão das aulas (RC = 0,41 [0,18-0,91]; p = 0,02) foram fatores protetores; e cursar o ciclo clínico foi fator de risco independente (RC = 2,74 [1,26-5,93]; p = 0,01) para depressão de moderada a grave. Conclusão: verificou-se uma alta prevalência de sintomas de ansiedade de moderada e grave, bem como de sintomas depressivos moderados. Um alta proporção dos estudantes apresentou grau de resiliência baixo ou muito baixo.

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 We report a rare case of an infective endocarditis by Aerococcus spp in a bioprosthetic aortic valve following a prostate biopsy, in an asymptomatic adult with no additional risk factor for prostate cancer, excepting for age. The diagnosis was based on the presence of vegetations on the bioprosthesis seen on the echocardiogram, positive blood cultures and fever, and a favorable clinical outcome following the treatment with ceftriaxone and gentamicin.

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 Fundamento: A doença de Fabry (DF) é uma doença de armazenamento lisossômico ligada ao cromossomo X, devido a mutações no gene da alfa galactosidase A (GLA), levando a deficiência enzimática de alfa-galactosidase (α-Gal A) e acúmulo de globotriaosilceramida (Gb3) e globotriaosilsulfingosina (liso-Gb3), causando disfunção de múltiplos órgãos. Objetivo: realizar a triagem do gene GLA em um grupo de pacientes com diagnóstico ecocardiográfico de cardiomiopatia hipertrófica (CMH). Métodos: estudo transversal realizado com pacientes com CMH em um hospital universitário. Pacientes com doença arterial coronariana e valvopatias foram excluídos. Foi realizada análise de mutação do gene GLA. Em indivíduos do sexo masculino, a análise foi realizada após evidência de baixa atividade de α-Gal A. Resultados: Foram incluídos 60 pacientes com diagnostico ecocardiográfico de CMH. A idade variou de 12 a 85 anos e 60% eram mulheres. O percentual médio de fibrose miocárdica na RM foi 10,7 ± 13,1% e a espessura ventricular média foi 18,7 ± 6,7 mm. Quatro pacientes tinham as seguintes mutações do GLA: c.967C>A (p.Pro323Thr), ainda não descrita na literatura; c.937G>T (p.Asp313Tyr); e c.352C>T (p.Arg118Cys). Todos os pacientes apresentavam níveis normais de liso-Gb3 e fibrose miocárdica não isquêmica na ressonância magnética; um paciente apresentou proteinúria; um paciente apresentou taquicardia ventricular. Conclusão: Neste estudo, a frequência de mutação no gene GLA em pacientes com CMH foi 6,7%. Uma nova mutação no exon 6 do gene GLA, c.967C>A (p.Pro323Thr), foi identificada. Pacientes com CMH podem ter mutações do GLA e a DF deve ser excluída. Os níveis plasmáticos de (liso-Gb3) não parecem ser suficientes para fazer um diagnóstico e biópsia de órgãos deve ser considerada.

Abstract Background: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the alpha galactosidase A gene (GLA) that lead to the enzymatic deficiency of alpha galactosidase (α-Gal A), resulting in the accumulation of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3), causing multiple organ dysfunctions. Objective: To perform GLA gene screening in a group of patients with echocardiographic diagnosis of hypertrophic cardiomyopathy (HCM). Methods: a cross-sectional study was conducted with HCM patients from a university hospital. Patients with coronary artery disease and valvulopathies were excluded. Mutation analysis of the GLA gene was performed. In male subjects, the analysis was performed after evidence of low α-Gal A activity. Results: 60 patients with echocardiographic diagnosis of HCM were included. Age ranged from 12 to 85 years and 60% were women. Mean myocardial fibrosis percentage on MRI was 10.7 ± 13.1% and mean ventricular thickness was18.7 ± 6.7 mm. Four patients had the following GLA gene mutations: c.967C>A (p.Pro323Thr), not yet described in the literature; c.937G>T (p.Asp313Tyr); and c.352C>T (p.Arg118Cys). All patients had normal levels of lyso-Gb3 and non-ischemic myocardial fibrosis on magnetic resonance imaging; one patient had proteinuria and one patient had ventricular tachycardia. Conclusion: in this study, the frequency of mutation in the GLA gene in patients with HCM was 6.7%. A novel mutation in exon 6 of the GLA gene, c.967C>A (p.Pro323Thr), was identified. Patients with HCM may have GLA mutations and FD should be ruled out. Plasma (lyso-Gb3) levels do not seem to be sufficient to attain a diagnosis and organ biopsy should be considered.

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 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.