Factors associated with oropharyngeal dysphagia in individuals with cardiovascular disease and COVID-19.

PURPOSE: Oropharyngeal dysphagia (OD) is one of the possible outcomes in patients hospitalized with COVID-19 and also in the population hospitalized for the treatment of cardiovascular disease. Thus, knowing the predictive risk factors for OD may help with referral and early intervention. This study aimed to verify the association of different factors with OD in hospitalized individuals with cardiovascular disease and COVID-19. METHODS: Cross-sectional clinical study approved by the Research Ethics Committee (4,521,771). Clinical evaluation of swallowing was carried out in 72 adult patients with cardiovascular disease and COVID-19 hospitalized from April to September 2020. Individuals under 18 years of age and without previous cardiovascular disease were excluded. The presence of general clinical and/or neurological complications, pronation, stay in the intensive care unit (ICU), orotracheal intubation (OTI), tracheostomy tube, oxygen support and age were considered as predictive risk factors for oropharyngeal dysphagia. Fisher's exact test, Mann Whitney test and logistic regression model were used for analysis. RESULTS: General clinical complications (p=0.001), pronation (p=0.003), ICU stay (p=0.043), in addition to the need for oxygen supplementation (p=0.023) and age (p= 0 .037) were statistically significant factors associated. The pronation (0.013) and age (0.038) were independently associated with dysphagia. OTI (p=0.208), tracheostomy (p=0.707) and the presence of previous cerebrovascular accidents (p=0.493) were not statistically significant. CONCLUSION: In this study, age and prone position were factors independently associated with oropharyngeal dysphagia, complications such as the need for oxygen supplementation, in addition to the need for ICU admission, were also associated factors in the population.

Immunogenicity of COVID-19 adsorbed inactivated vaccine (CoronaVac) and additional doses of mRNA BNT162b2 vaccine in immunocompromised adults compared with immunocompetent persons.

Inactivated COVID-19 vaccines data in immunocompromised individuals are scarce. This trial assessed the immunogenicity of two CoronaVac doses and additional BNT162b2 mRNA vaccine doses in immunocompromised (IC) and immunocompetent (H) individuals. Adults with solid organ transplant (SOT), hematopoietic stem cell transplant, cancer, inborn immunity errors or rheumatic diseases were included in the IC group. Immunocompetent adults were used as control group for comparison. Participants received two CoronaVac doses within a 28-day interval. IC received two additional BNT162b2 doses and H received a third BNT162b2 dose (booster). Blood samples were collected at baseline, 28 days after each dose, pre-booster and at the trial end. We used three serological tests to detect antibodies to SARS-CoV-2 nucleocapsid (N), trimeric spike (S), and receptor binding domain (RBD). Outcomes included seroconversion rates (SCR), geometric mean titers (GMT) and GMT ratio (GMTR). A total of 241 IC and 100 H adults participated in the study. After two CoronaVac doses, IC had lower SCR than H: anti-N, 33.3% vs 79%; anti-S, 33.8% vs 86%, and anti-RBD, 48.5% vs 85%, respectively. IC also showed lower GMT than H: anti-N, 2.3 vs 15.1; anti-S, 58.8 vs 213.2 BAU/mL; and anti-RBD, 22.4 vs 168.0 U/mL, respectively. After the 3rd and 4th BNT162b2 doses, IC had significant anti-S and anti-RBD seroconversion, but still lower than H after the 3rd dose. After boosting, GMT increased in IC, but remained lower than in the H group. CoronaVac two-dose schedule immunogenicity was lower in IC than in H. BNT162b2 heterologous booster enhanced immune response in both groups.

Methylation status of LDLR, PCSK9 and LDLRAP1 is associated with cardiovascular events in familial hypercholesterolemia

Aim: Methylation of LDLR, PCSK9 and LDLRAP1 CpG sites was assessed in patients with familialhypercholesterolemia (FH). Methods: DNA methylation of was analyzed by pyrosequencing in 131FH patients and 23 normolipidemic (NL) subjects. Results: LDLR, PCSK9 and LDLRP1 methylationwas similar between FH patients positive (MD) and negative (non-MD) for pathogenic variantsin FH-related genes. LDLR and PCSK9 methylation was higher in MD and non-MD groups thanNL subjects (p < 0.05). LDLR, PCSK9 and LDLRAP1 methylation profiles were associated withclinical manifestations and cardiovascular events in FH patients (p < 0.05). Conclusion: Differentialmethylation of LDLR, PCSK9 and LDLRAP1 is associated with hypercholesterolemia and cardiovascularevents. This methylation profile maybe useful as a biomarker and contribute to the management ofFH.

Analysing vaccine efficacy evaluated in phase 3 clinical trials carried out during outbreaks

In this paper we examine several definitions of vaccine efficacy (VE) that we found in the literature, for diseases that express themselves in outbreaks, that is, when the force of infection grows in time, reaches a maximum and then vanishes. The fact that the disease occurs in outbreaks results in several problems that we analyse. We propose a mathematical model that allows the calculation of VE for several scenarios. Vaccine trials usually needs a large number of volunteers that must be enrolled. Ideally, all volunteers should be enrolled in approximately the same time, but this is generally impossible for logistic reasons and they are enrolled in a fashion that can be replaced by a continuous density function (for example, a Gaussian function). The outbreak can also be replaced by a continuous density function, and the use of these density functions simplifies the calculations. Assuming, for example Gaussian functions, one of the problems one can immediately notice is that the peak of the two curves do not occur at the same time. The model allows us to conclude: First, the calculated vaccine efficacy decreases when the force of infection increases; Second, the calculated vaccine efficacy decreases when the gap between the peak in the force of infection and the peak in the enrollment rate increases; Third, different trial protocols can be simulated with this model; different vaccine efficacy definitions can be calculated and in our simulations, all result are approximately the same. The final, and perhaps most important conclusion of our model, is that vaccine efficacy calculated during outbreaks must be carefully examined and the best way we can suggest to overcome this problem is to stratify the enrolled volunteer's in a cohort-by-cohort basis and do the survival analysis for each cohort, or apply the Cox proportional hazards model for each cohort

Immunogenicity of COVID-19 adsorbed inactivated vaccine (CoronaVac) and additional doses of mRNA BNT162b2 vaccine in immunocompromised adults compared with immunocompetent persons

ABSTRACT Inactivated COVID-19 vaccines data in immunocompromised individuals are scarce. This trial assessed the immunogenicity of two CoronaVac doses and additional BNT162b2 mRNA vaccine doses in immunocompromised (IC) and immunocompetent (H) individuals. Adults with solid organ transplant (SOT), hematopoietic stem cell transplant, cancer, inborn immunity errors or rheumatic diseases were included in the IC group. Immunocompetent adults were used as control group for comparison. Participants received two CoronaVac doses within a 28-day interval. IC received two additional BNT162b2 doses and H received a third BNT162b2 dose (booster). Blood samples were collected at baseline, 28 days after each dose, pre-booster and at the trial end. We used three serological tests to detect antibodies to SARS-CoV-2 nucleocapsid (N), trimeric spike (S), and receptor binding domain (RBD). Outcomes included seroconversion rates (SCR), geometric mean titers (GMT) and GMT ratio (GMTR). A total of 241 IC and 100 H adults participated in the study. After two CoronaVac doses, IC had lower SCR than H: anti-N, 33.3% vs 79%; anti-S, 33.8% vs 86%, and anti-RBD, 48.5% vs 85%, respectively. IC also showed lower GMT than H: anti-N, 2.3 vs 15.1; anti-S, 58.8 vs 213.2 BAU/mL; and anti-RBD, 22.4 vs 168.0 U/mL, respectively. After the 3rd and 4th BNT162b2 doses, IC had significant anti-S and anti-RBD seroconversion, but still lower than H after the 3rd dose. After boosting, GMT increased in IC, but remained lower than in the H group. CoronaVac two-dose schedule immunogenicity was lower in IC than in H. BNT162b2 heterologous booster enhanced immune response in both groups.

Identification of pathogenic variants in the brazilian cohort with familial hypercholesterolemia using exon-targeted gene sequencing

Familial hypercholesterolemia (FH) is a monogenic disease characterized by high plasma low-density lipoprotein cholesterol (LDL-c) levels and increased risk of premature atherosclerotic cardiovascular disease. Mutations in FH-related genes account for 40% of FH cases worldwide. In this study, we aimed to assess the pathogenic variants in FH-related genes in the Brazilian FH cohort FHBGEP using exon-targeted gene sequencing (ETGS) strategy. FH patients (n = 210) were enrolled at five clinical sites and peripheral blood samples were obtained for laboratory testing and genomic DNA extraction. ETGS was performed using MiSeq platform (Illumina). To identify deleterious variants in LDLR, APOB, PCSK9, and LDLRAP1, the long-reads were subjected to Burrows-Wheeler Aligner (BWA) for alignment and mapping, followed by variant calling using Genome Analysis Toolkit (GATK) and ANNOVAR for variant annotation. The variants were further filtered using in-house custom scripts and classified according to the American College Medical Genetics and Genomics (ACMG) guidelines. A total of 174 variants were identified including 85 missense, 3 stop-gain, 9 splice-site, 6 InDel, and 71 in regulatory regions (3'UTR and 5'UTR). Fifty-two patients (24.7%) had 30 known pathogenic or likely pathogenic variants in FH-related genes according to the American College Medical and Genetics and Genomics guidelines. Fifty-three known variants were classified as benign, or likely benign and 87 known variants have shown uncertain significance. Four novel variants were discovered and classified as such due to their absence in existing databases. In conclusion, ETGS and in silico prediction studies are useful tools for screening deleterious variants and identification of novel variants in FH-related genes, they also contribute to the molecular diagnosis in the FHBGEP cohort.

Identification of pathogenic variants in the Brazilian cohort with Familial hypercholesterolemia using exon-targeted gene sequencing.

Familial hypercholesterolemia (FH) is a monogenic disease characterized by high plasma low-density lipoprotein cholesterol (LDL-c) levels and increased risk of premature atherosclerotic cardiovascular disease. Mutations in FH-related genes account for 40% of FH cases worldwide. In this study, we aimed to assess the pathogenic variants in FH-related genes in the Brazilian FH cohort FHBGEP using exon-targeted gene sequencing (ETGS) strategy. FH patients (n = 210) were enrolled at five clinical sites and peripheral blood samples were obtained for laboratory testing and genomic DNA extraction. ETGS was performed using MiSeq platform (Illumina). To identify deleterious variants in LDLR, APOB, PCSK9, and LDLRAP1, the long-reads were subjected to Burrows-Wheeler Aligner (BWA) for alignment and mapping, followed by variant calling using Genome Analysis Toolkit (GATK) and ANNOVAR for variant annotation. The variants were further filtered using in-house custom scripts and classified according to the American College Medical Genetics and Genomics (ACMG) guidelines. A total of 174 variants were identified including 85 missense, 3 stop-gain, 9 splice-site, 6 InDel, and 71 in regulatory regions (3'UTR and 5'UTR). Fifty-two patients (24.7%) had 30 known pathogenic or likely pathogenic variants in FH-related genes according to the American College Medical and Genetics and Genomics guidelines. Fifty-three known variants were classified as benign, or likely benign and 87 known variants have shown uncertain significance. Four novel variants were discovered and classified as such due to their absence in existing databases. In conclusion, ETGS and in silico prediction studies are useful tools for screening deleterious variants and identification of novel variants in FH-related genes, they also contribute to the molecular diagnosis in the FHBGEP cohort.

Antibody response dynamics to CoronaVac vaccine and booster immunization in adults and the elderly: A long-term, longitudinal prospective study.

Background: The long-term humoral immune response after vaccination varies between vaccines and is dependent on the accuracy of the antibody test. A better understanding of the vaccine immune response may help to define vaccination strategies against coronavirus disease 2019 (COVID-19). Objective: To investigate the long-term immunological response to CoronaVac vaccine and determinants of breakthrough COVID-19 infection. Methods: A long-term, prospective cohort study involving vaccinated adult and elderly subjects was conducted to investigate the presence of anti-RBD-specific immunoglobulin (Ig)G, anti-nucleocapsid IgG and anti-spike trimeric protein IgG. Antibody level dynamics and risk factors associated with breakthrough COVID-19 infection were investigated. Results: In total, 3902 participants were included in this study. Vaccination with two doses of CoronaVac and a booster dose increased the levels of anti-RBD-specific IgG, anti-nucleocapsid IgG and anti-spike trimeric IgG significantly. In adults, anti-nucleocapsid IgG and anti-spike trimeric IgG levels decreased significantly 7 months after the second dose. In adults and the elderly, the levels of anti-spike trimeric IgG and anti-RBD IgG decreased significantly 4 and 6 months after the booster dose, respectively. Previous exposure to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and anti-spike trimeric IgG titres was independently associated with a lower probability of post-vaccination infection. Conclusions: A significant increase in antibody levels was found after two doses of CoronaVac and a booster dose. Antibody titres declined significantly 7 months post-vaccination in participants who did not receive a booster dose. Higher levels of antibodies and previous SARS-CoV-2 infection were associated with protection against breakthrough COVID-19.

Coronary artery bypass grafting in young patients - a brazilian retrospective cohort study

BACKGROUND: The prevalence of early Coronary Artery Disease (CAD) (i.e., patients under 45 years) is increasing, which entails an equal rise in disability-adjusted life years due to disease burden. Risk factors in this population are not entirely elucidated. Hence, our objectives were to evaluate the clinical characteristics, risk factors, and outcomes in patients under 45 and over 45 years undergoing Coronary Artery Bypass Grafting (CABG). METHODS: We performed a retrospective-comparative cohort between patients under and over 45 years, who underwent CABG at Instituto Dante Pazzanese de Cardiologia, in São Paulo/Brazil, from 1999 to 2015. Patientsʼ characteristics were evaluated by Fisher Exact Test, and risk factors for in-hospital mortality were assessed by Stepwise Logistic Regression. Survival analysis was performed by Kaplan Meier and Log Rank Test. RESULTS: During the study timeframe, 8,889 patients underwent surgery and, out of those, 408 were young. The follow-up period ranged from 10 days to 257 months. Patients under 45 years were associated with higher rates of hypertriglyceridemia, current smoking, previous myocardial infarction and family history of coronary artery disease. Further, they presented higher rates of single vessel disease (11% versus 5.4%, p<0.001), with higher incidence of isolated occlusion of the left anterior descending artery (10.8% versus 5.1%, p<0.001). The younger group had a higher number of coronary artery bypass grafts (2.75±0.82 versus 2.6±0.88, p<0.001). Finally, they were also associated with lower in-hospital mortality (1.7% versus 5.1%, p=0.001). Survival estimates in 10 and 15 years among patients under 45 years were 91.7% and 87.7%, respectively, with an average lifespan of 237,21 months. CONCLUSION: Although hypertriglyceridemia, smoking and family history are well-recognized risk factors for CAD, they may play a more significant role in younger patients. Additionally, this study showed that CAD has a different clinical course in patients under 45 years, which urges the need to readdress how these patients are screened, evaluated and treated. To our knowledge, this is the first Brazilian study to assess this special population.

Antibody response dynamics to CoronaVac vaccine and booster immunization in adults and the elderly: a long-term, longitudinal prospective study

Background The long-term humoral immune response after vaccination varies between vaccines and is dependent on the accuracy of the antibody test. A better understanding of the vaccine immune response may help to define vaccination strategies against coronavirus disease 2019 (COVID-19). Objective To investigate the long-term immunological response to CoronaVac vaccine and determinants of breakthrough COVID-19 infection. Methods A long-term, prospective cohort study involving vaccinated adult and elderly subjects was conducted to investigate the presence of anti-RBD-specific immunoglobulin (Ig)G, anti-nucleocapsid IgG and anti-spike trimeric protein IgG. Antibody level dynamics and risk factors associated with breakthrough COVID-19 infection were investigated. Results In total, 3902 participants were included in this study. Vaccination with two doses of CoronaVac and a booster dose increased the levels of anti-RBD-specific IgG, anti-nucleocapsid IgG and anti-spike trimeric IgG significantly. In adults, anti-nucleocapsid IgG and anti-spike trimeric IgG levels decreased significantly 7 months after the second dose. In adults and the elderly, the levels of anti-spike trimeric IgG and anti-RBD IgG decreased significantly 4 and 6 months after the booster dose, respectively. Previous exposure to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and anti-spike trimeric IgG titres was independently associated with a lower probability of post-vaccination infection. Conclusions A significant increase in antibody levels was found after two doses of CoronaVac and a booster dose. Antibody titres declined significantly 7 months post-vaccination in participants who did not receive a booster dose. Higher levels of antibodies and previous SARS-CoV-2 infection were associated with protection against breakthrough COVID-19.

Amplitude das Ondas F como Preditor de Tromboembolismo e de Sucesso da Cardioversão Elétrica em Pacientes com Fibrilação Atrial Persistente / F Wave Amplitude as a Predictor of Thromboembolism and Success of Electrical Cardioversion in Patients with Persistent Atrial Fibrillation

Resumo Fundamento A fibrilação atrial (FA) é classificada, de acordo com a amplitude das ondas fibrilatórias (f), em ondas finas (FAf) e ondas grossas (FAg). Objetivos Correlacionar a amplitude das ondas f com variáveis clínicas, laboratoriais, eletrocardiográficas e ecocardiográficas que indiquem alto risco de tromboembolismo e avaliar o seu impacto no sucesso da cardioversão elétrica (CVE). Métodos Estudo retrospectivo, observacional, que incluiu 57 pacientes com FA não valvar persistente submetidos a CVE. A amplitude máxima das ondas f foi aferida na derivação V1. FAg foi definida quando f≥1,0 mm e FAf quando f<1,0mm. Os achados foram correlacionados com as variáveis indicadas. Valores de p<0,05 foram considerados estatisticamente significativos. Resultados FAg (n=35) associou-se a maior sucesso na CVE (94,3% vs. 72,7%, p=0,036) mesmo após ajuste para variáveis como idade e IMC (p=0,026, OR=11,8). Pacientes com FAf (n=22) necessitaram mais choques e maior energia para reversão ao ritmo sinusal (p=0,019 e p=0,027, respectivamente). Não houve associação significativa entre a amplitude das ondas f e parâmetros clínicos, ecocardiográficos e laboratoriais. Conclusões A amplitude de f não se associou a parâmetros ecocardiográficos, clínicos e laboratoriais que indicam alto risco de tromboembolismo. FAg associou-se a maior chance de sucesso na reversão ao ritmo sinusal por meio da CVE. Maior número de choques e energia foram necessários para reversão ao ritmo sinusal em pacientes com FAf.

Abstract Background Atrial fibrillation (AF) is classified according to the amplitude of fibrillatory waves (f) into fine waves (fAF) and coarse waves (cAF). Objectives To correlate the amplitude of f waves with clinical, laboratory, electrocardiographic, and echocardiographic variables that indicate a high risk of thromboembolism and to assess their impact on the success of electrical cardioversion (ECV). Methods Retrospective, observational study that included 57 patients with persistent non-valvular AF who underwent ECV. The maximum amplitude of f waves was measured in lead V1. cAF was defined when f ≥ 1.0mm and fAF when f < 1.0mm. The findings were correlated with the indicated variables. Values of p < 0.05 were considered statistically significant. Results cAF (n = 35) was associated with greater success in ECV (94.3% vs. 72.7%, p = 0.036) even after adjusting for variables such as age and BMI (p = 0.026, OR = 11.8). Patients with fAF (n = 22) required more shocks and more energy to revert to sinus rhythm (p = 0.019 and p = 0.027, respectively). There was no significant association between f-wave amplitude and clinical, echocardiographic, and laboratory parameters. Conclusions The amplitude of f wave was not associated with echocardiographic, clinical and laboratory parameters that indicate a high risk of thromboembolism. cAF was associated with a higher chance of success reverting to sinus rhythm employing ECV. A greater number of shocks and energy were required for reversion to sinus rhythm in patients with fAF.

F Wave Amplitude as a Predictor of Thromboembolism and Success of Electrical Cardioversion in Patients with Persistent Atrial Fibrillation. / Amplitude das Ondas F como Preditor de Tromboembolismo e de Sucesso da Cardioversão Elétrica em Pacientes com Fibrilação Atrial Persistente.

BACKGROUND: Atrial fibrillation (AF) is classified according to the amplitude of fibrillatory waves (f) into fine waves (fAF) and coarse waves (cAF). OBJECTIVES: To correlate the amplitude of f waves with clinical, laboratory, electrocardiographic, and echocardiographic variables that indicate a high risk of thromboembolism and to assess their impact on the success of electrical cardioversion (ECV). METHODS: Retrospective, observational study that included 57 patients with persistent non-valvular AF who underwent ECV. The maximum amplitude of f waves was measured in lead V1. cAF was defined when f ≥ 1.0mm and fAF when f < 1.0mm. The findings were correlated with the indicated variables. Values of p < 0.05 were considered statistically significant. RESULTS: cAF (n = 35) was associated with greater success in ECV (94.3% vs. 72.7%, p = 0.036) even after adjusting for variables such as age and BMI (p = 0.026, OR = 11.8). Patients with fAF (n = 22) required more shocks and more energy to revert to sinus rhythm (p = 0.019 and p = 0.027, respectively). There was no significant association between f-wave amplitude and clinical, echocardiographic, and laboratory parameters. CONCLUSIONS: The amplitude of f wave was not associated with echocardiographic, clinical and laboratory parameters that indicate a high risk of thromboembolism. cAF was associated with a higher chance of success reverting to sinus rhythm employing ECV. A greater number of shocks and energy were required for reversion to sinus rhythm in patients with fAF.

FUNDAMENTO: A fibrilação atrial (FA) é classificada, de acordo com a amplitude das ondas fibrilatórias (f), em ondas finas (FAf) e ondas grossas (FAg). OBJETIVOS: Correlacionar a amplitude das ondas f com variáveis clínicas, laboratoriais, eletrocardiográficas e ecocardiográficas que indiquem alto risco de tromboembolismo e avaliar o seu impacto no sucesso da cardioversão elétrica (CVE). MÉTODOS: Estudo retrospectivo, observacional, que incluiu 57 pacientes com FA não valvar persistente submetidos a CVE. A amplitude máxima das ondas f foi aferida na derivação V1. FAg foi definida quando f≥1,0 mm e FAf quando f<1,0mm. Os achados foram correlacionados com as variáveis indicadas. Valores de p<0,05 foram considerados estatisticamente significativos. RESULTADOS: FAg (n=35) associou-se a maior sucesso na CVE (94,3% vs. 72,7%, p=0,036) mesmo após ajuste para variáveis como idade e IMC (p=0,026, OR=11,8). Pacientes com FAf (n=22) necessitaram mais choques e maior energia para reversão ao ritmo sinusal (p=0,019 e p=0,027, respectivamente). Não houve associação significativa entre a amplitude das ondas f e parâmetros clínicos, ecocardiográficos e laboratoriais. CONCLUSÕES: A amplitude de f não se associou a parâmetros ecocardiográficos, clínicos e laboratoriais que indicam alto risco de tromboembolismo. FAg associou-se a maior chance de sucesso na reversão ao ritmo sinusal por meio da CVE. Maior número de choques e energia foram necessários para reversão ao ritmo sinusal em pacientes com FAf.

HIGH VALUES OF LIVER STIFFNESS PLAY AN IMPORTANT ROLE IN STRATIFYING THE RISK OF HEPATOCELLULAR CARCINOMA IN CIRRHOTIC HEPATITIS C PATIENTS.

BACKGROUND: Evaluate the role of liver stiffness measurement (LSM) by transient elastography (TE) as a risk factor for hepatocellular carcinoma (HCC) occurrence in a prospective cohort of Brazilian hepatitis C virus (HCV) patients with cirrhosis. METHODS: A cohort of 99 consecutive HCV patients was included between 2011 and 2016 with baseline LSM ≥12 kilopascals (kPa). Baseline variables were evaluated and HCC occurrence was documented. Kaplan-Meier methods with a log-rank test and the use of cox univariate and multivariate analysis assessed the association between variables and clinical results. RESULTS: The mean age was 57.8±10.6 years. In a follow-up over a mean of 3.3 years, 20 (20.2%) patients developed HCC. In univariate logistic regression analysis, variables associated with HCC occurrence were: lower platelet count (P=0.0446), higher serum alpha-fetoprotein (P=0.0041) and bilirubin (P=0.0008) values, higher Model for End-Stage Liver Disease (MELD) score (P=0.0068) and higher LSM (P=0.0354). LSM evaluated by TE was independently associated with HCC development, and the best cut-off value for higher HCC risk was >21.1 kPa (HR: 5.548; 95%CI: 1.244-24.766; P=0.025). CONCLUSION: A high value of liver stiffness relates substantially to an increased risk for HCC occurrence in Brazilian patients with cirrhosis due to HCV.

Altos valores de rigidez hepática desempenham um papel importante na estratificação do risco de carcinoma hepatocelular em pacientes cirróticos com vírus C / High values of liver stiffness play an important role in stratifying the risk of hepatocellular carcinoma in cirrhotic hepatitis c patients

ABSTRACT Background: Evaluate the role of liver stiffness measurement (LSM) by transient elastography (TE) as a risk factor for hepatocellular carcinoma (HCC) occurrence in a prospective cohort of Brazilian hepatitis C virus (HCV) patients with cirrhosis. Methods: A cohort of 99 consecutive HCV patients was included between 2011 and 2016 with baseline LSM ≥12 kilopascals (kPa). Baseline variables were evaluated and HCC occurrence was documented. Kaplan-Meier methods with a log-rank test and the use of cox univariate and multivariate analysis assessed the association between variables and clinical results. Results: The mean age was 57.8±10.6 years. In a follow-up over a mean of 3.3 years, 20 (20.2%) patients developed HCC. In univariate logistic regression analysis, variables associated with HCC occurrence were: lower platelet count (P=0.0446), higher serum alpha-fetoprotein (P=0.0041) and bilirubin (P=0.0008) values, higher Model for End-Stage Liver Disease (MELD) score (P=0.0068) and higher LSM (P=0.0354). LSM evaluated by TE was independently associated with HCC development, and the best cut-off value for higher HCC risk was >21.1 kPa (HR: 5.548; 95%CI: 1.244-24.766; P=0.025). Conclusion: A high value of liver stiffness relates substantially to an increased risk for HCC occurrence in Brazilian patients with cirrhosis due to HCV.

RESUMO Contexto: O carcinoma hepatocelular (CHC) é o tumor maligno hepático mais comum, e a cirrose é o principal fator de risco para o seu desenvolvimento. Objetivo: Avaliar o papel da medição da rigidez hepática por elastografia transitória (ET) como fator de risco para ocorrência de CHC em uma coorte prospectiva de pacientes brasileiros com cirrose por vírus da hepatite C (VHC). Métodos: Um total de 99 pacientes com VHC e medida de rigidez hepática ≥12 kilopascals (kPa) foram incluídos consecutivamente, entre 2011 e 2016. As variáveis do baseline foram avaliadas e a ocorrência de CHC foi documentada. Os testes de Kaplan-Meier e log-rank, além das análises uni e multivariadas de Cox avaliaram a associação entre as variáveis e os resultados clínicos. Resultados: A média de idade foi de 57,8±10,6 anos. Vinte (20,2%) pacientes desenvolveram CHC, num período médio de seguimento de 3,3 anos. Na análise de regressão logística univariada, as variáveis associadas à ocorrência de CHC foram: contagem de plaquetas mais baixa (P=0,0446), valores séricos mais elevados de alfa-fetoproteína (P=0,0041) e de bilirrubina (P=0,0008), maior pontuação do escore MELD (P=0,0068) e valores mais altos de rigidez hepática por ET (P=0,0354). A medição da rigidez hepática por ET foi independentemente associada ao desenvolvimento de CHC, e o melhor valor de corte para maior risco de CHC foi >21,1kPa (HR: 5,548; IC95%: 1,244-24,766; P=0,025). Conclusão: Um alto valor de rigidez hepática está relacionado substancialmente a um risco aumentado de ocorrência de CHC em pacientes brasileiros com cirrose por HCV.

Universal Definition of Myocardial Infarction 99th Percentile versus Diagnostic Cut-off Value of Troponin I for Acute Coronary Syndromes. / Troponina I por Percentil 99 da Definição Universal de Infarto do Miocárdio versus Ponto de Corte de Melhor Acurácia em Síndromes Coronárias Agudas.

BACKGROUND: Contemporary diagnosis of ACS and risk stratification are essential for appropriate management and reduction of mortality and recurrent ischemic events, in the acute phase of disease and after hospitalization. The Universal Definition of Myocardial Infarction recommends the detection of troponin levels above the 99th percentile. OBJECTIVES: To evaluate the occurrence of early death and acute myocardial infarction (AMI) in patients without elevation of troponin (<0.034 ng/mL), patients with mild elevation (above the 99th percentile [>0.034 ng/mL and <0.12 ng/mL)], and patients with significant elevation of troponin (above the diagnostic cutoff for AMI defined by the troponin kit (≥0.12 ng/mL)]; and to analyze the impact of troponin on the indication for invasive strategy and myocardial revascularization. METHODS: Cross-sectional cohort study of patients with ACS with assessment of peak troponin I, risk score, prospective analysis of 30-day clinical outcomes and two-sided statistical tests, with statistical significance set at p<0.05. RESULTS: A total of 494 patients with ACS were evaluated. Troponin > 99th percentile and below the cutoff point, as well as values above the cutoff, were associated with higher incidence of composite endpoint (p<0.01) and higher rates of percutaneous or surgical revascularization procedures (p<0.01), without significative difference in 30-day mortality. CONCLUSIONS: Troponin levels above the 99th percentile defined by the universal definition of AMI play a prognostic role and add useful information to the clinical diagnosis and risk scores by identifying those patients who would most benefit from invasive risk stratification and coronary revascularization procedures.

FUNDAMENTO: O diagnóstico de síndrome coronária aguda (SCA) e a estratificação de risco contemporâneos são fundamentais para o manejo apropriado e redução da mortalidade e eventos isquêmicos recorrentes, tanto na fase aguda quanto após hospitalização. A Definição Universal de Infarto do Miocárdio recomenda a detecção de curva de troponina acima do limite superior do percentil 99. OBJETIVOS: Avaliar a ocorrência de óbito e infarto agudo do miocárdio (IAM) na fase precoce em pacientes sem elevação de troponina (<0,034 ng/mL), pacientes com mínima elevação [acima do percentil 99 (>0,034 ng/mL e <0,12 ng/mL)], e pacientes com maiores elevações [acima do ponto de corte para IAM pelo kit utilizado (≥0,12 ng/mL)]; e avaliar o impacto dos níveis de troponina na indicação de estratégia invasiva e revascularização miocárdica. MÉTODOS: Estudo de corte transversal de pacientes com SCA com avaliação do pico da troponina I, escores de risco, análise prospectiva de desfechos clínicos até 30 dias e testes bilaterais de significância, com nível de significância adotado sendo < 0,05. RESULTADOS: Foram avaliados 494 pacientes com SCA. Troponina > percentil 99 e abaixo do ponto de corte, assim como valores maiores (acima do ponto de corte), foram associados à maior incidência do desfecho composto (p<0,01) e de revascularização percutânea ou cirúrgica (p<0,01), sem diferença significante em mortalidade até 30 dias. CONCLUSÕES: Valores de troponina elevados acima do percentil 99 pela Definição Universal de IAM apresentam papel prognóstico e agregam informação útil ao diagnóstico clínico e escores de risco na identificação de pacientes com maior probabilidade de benefício com estratificação invasiva e procedimentos de revascularização coronária.

Troponina I por percentil 99 da definição universal de infarto do miocárdio versus ponto de corte de melhor acurácia em síndromes coronárias agudas / Universal definition of myocardial infarction 99th percentile versus diagnostic cut-off value of troponin I for acute coronary syndromes

FUNDAMENTO: O diagnóstico de síndrome coronária aguda (SCA) e a estratificação de risco contemporâneos são fundamentais para o manejo apropriado e redução da mortalidade e eventos isquêmicos recorrentes, tanto na fase aguda quanto após hospitalização. A Definição Universal de Infarto do Miocárdio recomenda a detecção de curva de troponina acima do limite superior do percentil 99. OBJETIVOS: Avaliar a ocorrência de óbito e infarto agudo do miocárdio (IAM) na fase precoce em pacientes sem elevação de troponina (<0,034 ng/mL), pacientes com mínima elevação [acima do percentil 99 (>0,034 ng/mL e <0,12 ng/mL)], e pacientes com maiores elevações [acima do ponto de corte para IAM pelo kit utilizado (≥0,12 ng/mL)]; e avaliar o impacto dos níveis de troponina na indicação de estratégia invasiva e revascularização miocárdica. MÉTODOS: Estudo de corte transversal de pacientes com SCA com avaliação do pico da troponina I, escores de risco, análise prospectiva de desfechos clínicos até 30 dias e testes bilaterais de significância, com nível de significância adotado sendo < 0,05. RESULTADOS: Foram avaliados 494 pacientes com SCA. Troponina > percentil 99 e abaixo do ponto de corte, assim como valores maiores (acima do ponto de corte), foram associados à maior incidência do desfecho composto (p<0,01) e de revascularização percutânea ou cirúrgica (p<0,01), sem diferença significante em mortalidade até 30 dias. CONCLUSÕES: Valores de troponina elevados acima do percentil 99 pela Definição Universal de IAM apresentam papel prognóstico e agregam informação útil ao diagnóstico clínico e escores de risco na identificação de pacientes com maior probabilidade de benefício com estratificação invasiva e procedimentos de revascularização coronária.

BACKGROUND: Contemporary diagnosis of ACS and risk stratification are essential for appropriate management and reduction of mortality and recurrent ischemic events, in the acute phase of disease and after hospitalization. The Universal Definition of Myocardial Infarction recommends the detection of troponin levels above the 99th percentile. OBJECTIVES: To evaluate the occurrence of early death and acute myocardial infarction (AMI) in patients without elevation of troponin (<0.034 ng/mL), patients with mild elevation (above the 99th percentile [>0.034 ng/mL and <0,12 ng/mL)], and patients with significant elevation of troponin (above the diagnostic cutoff for AMI defined by the troponin kit (≥0.12 ng/mL)]; and to analyze the impact of troponin on the indication for invasive strategy and myocardial revascularization. METHODS: cross-sectional cohort study of patients with ACS with assessment of peak troponin I, risk score, prospective analysis of 30-day clinical outcomes and two-sided statistical tests, with statistical significance set at p<0.05. RESULTS: A total of 494 patients with ACS were evaluated. Troponin > 99the percentile and below the cutoff point, as well as values above the cutoff, were associated with higher incidence of composite endpoint (p<0.01) and higher rates of percutaneous or surgical revascularization procedures (p<0.01), without significative difference in 30-day mortality. CONCLUSIONS: troponin levels above the 99the percentile defined by the universal definition of AMI play a prognostic role and add useful information to the clinical diagnosis and risk scores by identifying those patients who would most benefit from invasive risk stratification and coronary revascularization procedures.

Preditores de complicações em pós-operatório de cirúrgia cardíaca pediátrica / Predictors of complications in the postoperative period of pediatric cardiac surgery

RESUMO | Objetivo: Identificar preditores de complicação no pós-operatório de cirurgia cardíaca pediátrica. METODO: Estudo quantitativo que analisou retrospectivamente 88 prontuários de pacientes submetidos a procedimento cirúrgico no ano de 2018. Para analise dos dados foi aplicado o teste exato de Fisher e o modelo logístico univariado. Os resultados foram expressos pelo odds ratio (OR) com nível de significância de 5%. RESULTADOS: observou-se idade média de 3,61 anos com predominância do sexo feminino. Complicações circulatórias, metabólicas, renais, respiratórias e cardiovasculares foram identificadas intra e pós-operatória. Foi identificada correlação estatística preditiva de complicações em: uso de diuréticos, hipertensão arterial, insuficiência de valva atrioventricular, hipertrofia de ventrículo direito, trissomia de cromossomo 21, leucócitos alterados nos pré-operatórios, sangramento intraoperatório, derrame pericárdico e alterações no ecocardiograma pós-operatório. CONCLUSÃO: Variáveis de condições clínicas, medicações em uso, defeitos congênitos e intercorrências intraoperatórias quando associados às complicações encontradas no pós-operatório de cirurgias cardiopediátricas mostram-se como preditivos de risco.

ABSTRACT | Objective: To identify predictors of complications in the postoperative period of pediatric cardiac surgery. METHOD: Quantitative study that retrospectively analyzed 88 medical records of patients undergoing surgical procedure in 2018. Fisher's exact test and the univariate logistic model were applied to analyze the data. The results were expressed by odds ratio (OR) with a significance level of 5%. RESULTS: A mean age of 3.61 years was observed, with a predominance of females. Circulatory, metabolic, renal, respiratory and cardiovascular complications were identified intra-and postoperatively. A predictive statistical correlation of complications was identified in: use of diuretics, hypertension, atrioventricular valve insufficiency, right ventricular hypertrophy, trisomy 21, altered WBCs preoperatively, intraoperative bleeding, pericardial effusion and postoperative echocardiogram changes. CONCLUSION: Variables of clinical conditions, medications in use, congenital defects and intraoperative complications when associated with complications found in the postoperative period of cardiopediatric surgeries are shown to be predictive of risk.

RESUMEN | Objetivo: Identificar los predictores de complicaciones en el postoperatorio de la cirugía cardiaca pediátrica. MÉTODO: Estudio cuantitativo retrospectivo de 88 historias clínicas de pacientes operados en 2018. Se aplicó la prueba exacta de Fisher y el modelo logístico univariante. Los resultados se expresaron mediante odds ratio (OR) con una significación del 5%. RESULTADOS: La edad media era de 3,61 años con mayoría de mujeres. Se indentificaron complicaciones circulatorias, metabólicas, renales, respiratorias y cardiovasculares intra y postoperatorias. Se identificó una correlación estadística predictiva de complicaciones en: el uso de diuréticos, la hipertensión arterial, la insuficiencia valvular auriculoventricular, la hipertrofia ventricular derecha, la trisomía 21, la alteración de los leucocitos preoperatorios, la hemorragia intraoperatoria, el derrame pericárdico y las alteraciones en el ecocardiograma postoperatorio. CONCLUSIÓN: Las variables del estado clínico, los medicamentos en uso, los defectos congénitos y las complicaciones intraoperatorias cuando se asocian a las complicaciones encontradas en el postoperatorio de las cirurgías cardiopediátricas se muestran como predictoras de riesgo.

Sobrevida e principais intervenções de enfermagem em pacientes pediátricos em uso da oxigenação por membrana extracorpórea / Survival and main nursing interventions in pediatric patients using extracorporeal membrane oxygenation / Supervivencia y principales intervenciones de enfermería en pacientes pediátricos mediante oxigenación por membrana extracorpórea

Objetivo: Identificar intervenções de enfermagem e analisar a sobrevida de pacientes pediátricos que utilizaram oxigenação por membrana extracorpórea no pós-operatório de Cirurgia Cardíaca. Método: Trata-se de um estudo observacional prospectivo histórico de abordagem quantitativa. Foram obtidos dados sobre as principais intervenções de enfermagem nos prontuários período do pós-operatório imediato. Posteriormente foi realizado contato telefônico para analisar a sobrevida das crianças que utilizaram ECMO no pós-operatório de cirurgia cardíaca. Resultado: Evidenciou a predominância sexo masculino 68,8%, lactentes 66,7%, etnia branca 83,3%. Encontrou-se 82 intervenções de enfermagem. Nos pacientes que apresentaram alta hospitalar (33,3%), foi realizado o follow up. Conclusão: As principais intervenções de enfermagem, para os pacientes pediátricos pós-cirurgia cardíaca em uso de ECMO identificados nesse estudo foram: monitorização multiparamétrica, cuidados para prevenção e/ou controle do sangramento, mudança de decúbito, troca de curativo e observação de mudança clínica do paciente. (AU)

Objective: To identify nursing interventions and analyze the survival of pediatric patients who used extracorporeal membrane oxygenation in the post-op period of cardiac surgery. Methods: This is a prospective historical observational study with a quantitative approach. Data on the main nursing interventions were captured in the medical records during the immediate postoperative period. Subsequently, telephone contact was made to analyze the survival of children who used extracorporeal membrane oxygenation in the postoperative period of cardiac surgery. Results: There was a predominance of male gender 68.8%, infants 66.7%, white ethnicity 83.3%. We found 82 nursing procedures. In the patients who had hospital discharge (33.3%), it was performed for follow-up. Conclusion: The main nursing interventions for pediatric patients after cardiac surgery using extracorporeal membrane oxygenation indicated in this study were: multiparametric monitoring, care for prevention and / or control of bleeding, change of decubitus position, bandage change and observation of the patient's clinical change. (AU)

Objetivo: Identificar intervenciones de enfermería y analizar la supervivencia de pacientes pediátricos que utilizaron oxigenación por membrana extracorpórea en el postoperatorio de cirugía cardíaca. Métodos: Se trata de un estudio observacional histórico prospectivo con enfoque cuantitativo. Los datos sobre las principales intervenciones de enfermería se obtuvieron de las historias clínicas en el postoperatorio inmediato. Posteriormente, se realizó contacto telefónico para analizar la supervivencia de los niños que utilizaron oxigenación por membrana extracorpórea en el postoperatorio de cirugía cardíaca. Resultados: Predominó el sexo masculino 68,8%, lactantes 66,7%, etnia blanca 83,3%. Se encontraron 82 intervenciones de enfermería. En los pacientes dados de alta hospitalaria (33,3%), la follow up. Conclusión: Las principales intervenciones de enfermería para pacientes pediátricos postoperatorios de cirugía cardíaca mediante oxigenación por membrana extracorpórea identificadas en este estudio fueron: monitorización multiparamétrica, cuidados para la prevención y / o control de hemorragias, cambio de decúbito, cambio de apósito y observación del cambio clínico del paciente. (AU)

Cirurgia de revascularização miocárdica em pacientes jovens / Myocardial revascularization surgery in young patients

OBJETIVOS: Estão disponíveis na literatura poucos estudos, ou ainda, séries com pequeno número de pacientes na área de cirurgia de revascularização miocárdica envolvendo pacientes jovens. Neste estudo foi avaliada a morbimortalidade hospitalar, assim como a evolução a longo prazo, de pacientes jovens, com idades inferior ou igual a 45 anos, submetidos à cirurgia de revascularização do miocárdio isolada (CRM). MÉTODOS: Análise retrospectiva da morbimortalidade hospitalar e evolução a longo prazo de todos os pacientes jovens com idades ≤ 45 anos, consecutivamente submetidos à CRM no período de 01/01/1999 a 31/12/2015. RESULTADOS: No período avaliado, 8889 pacientes foram submetidos a cirurgia, sendo 408 pacientes jovens (4,5%). Os pacientes com idade ≤ 45 anos apresentaram mais frequentemente história de tabagismo, hipertrigliceridemia, história familiar positiva e infarto agudo do miocárdio (IAM) prévio, enquanto os pacientes com idade > 45 anos eram mais sintomáticos no momento da cirurgia. Enxertos com artéria torácica interna foram mais utilizados nos jovens, 96,1% versus 91,8%, p < 0,001. Os pacientes com idade < 45 anos apresentaram baixas taxas de complicações pós-operatórias. A mortalidade hospitalar foi de 1,7% e 5,1% em jovens e idosos respectivamente. A sobrevida da população jovem a longo prazo foi de 91,73% e 87,74% em 10 e 15 anos respectivamente, segundo modelo de Kaplan-Meier. CONCLUSÕES: Os pacientes com idade ≤ 45 anos apresentavam mais frequentemente história de tabagismo atual, hipertrigliceridemia, história familiar positiva para doença arterial coronária (DAC) e infarto prévio, quando comparados aos mais idosos. A cirurgia de revascularização na população jovem apresenta ótimos resultados, com baixas taxas de complicações e mortalidade hospitalar.

Minimum Alveolar Concentration of Sevoflurane as a Single Hypnotic Agent to Maintain BIS Below 50 in Patients During Normothermic Cardiopulmonary Bypass

OBJECTIVES: Minimum alveolar concentration (MAC) of volatile anesthetic agents to maintain bispectral index (BIS) below 50 in 50% of patients was defined as MACBIS50. The primary objective of this study was to determine the minimum alveolar concentration of sevoflurane as a single hypnotic agent to maintain BIS below 50 in patients during normothermic cardiopulmonary bypass. DESIGN: Prospective and observational study. SETTING: Dante Pazzanese Institute of Cardiology, Brazil. PARTICIPANTS: Eighteen consecutive patients scheduled for elective coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) under general anesthesia, American Society of Anesthesiologists physical status classes III and IV, between the ages of 40 and 70, were included in the study. METHODS: All patients underwent inhalation induction with facial mask using sevoflurane (Cristália) in 100% oxygen, pancuronium (Cristália) 0.1 mg/kg, and sufentanil (Cristália) 0.5 µg/kg intravenously (IV) administered. A single bolus dose of sufentanil, 1.0 µg/kg IV, was administered before surgical incision. MACBIS50 was calculated using the midpoint concentration of patients involving a crossover (BIS < or ≥50) according to Dixon's Up-and-Down method. The Up-and-Down sequence also was analyzed by probit test that enabled the authors to obtain the effective dose 50 (ED50) and effective dose 95 (ED95) of sevoflurane to maintain a BIS value <50, with a 95% confidence interval (95% CI) of the mean. RESULTS: A total of 15 patients were analyzed in this study. MACBIS50 of sevoflurane as a single hypnotic agent was 0.82% (95% CI 0.47-1.16) in patients aged 40 to 70 undergoing CABG during normothermic CPB. The ED50 and ED95 of sevoflurane to maintain a BIS value <50 for the same context were 0.73% (95% CI 0.45-1.00) and 1.39 (95% CI 0.42-2.37) by means of probit analysis, respectively. CONCLUSION: MACBIS50 of sevoflurane as a single hypnotic agent was 0.82% in patients undergoing CABG during normothermic CPB.