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.

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.

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.

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.

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.

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.

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.

Prevalence of Low Back Pain and Associated Factors in Older Adults: Amazonia Brazilian Community Study.

To investigate the prevalence of low back pain (LBP) and associated factors in the older adult Amazonia Brazilian community, a cross-sectional study was conducted to evaluate 700 participants that were ≥60 years old. Pain intensity and functional disability were assessed using the Numerical Pain Scale and the Roland Morris Questionnaire, respectively, and their sociodemographic, clinical, and behavior variables were collected, i.e., age, sex, education level, socioeconomic level, anthropometric measurements, physical activity, health perception, and emotional state. The punctual prevalence rates of LBP were 42.4% (95% CI: 38.2-46.6%), and for the last 365 days, these prevalence rates were 93.7% (95% CI: 91.3-95.6%), the mean pain and functional disability scores were 6.17 ± 2.13 and 11.30 ± 6.07, and the moderate-to-severe disability was 39.7%. Pain and functional disability were associated with sex, chronic diseases, body mass index (BMI), physical activity level, health perception, and emotional level. In conclusion, the prevalence of LBP was high (for both punctual and the last 365 days), but the variables associated with being female, fewer years of schooling, sedentary behavior, diseases related to diet and the cardiovascular system, and impaired emotional levels had a higher level LBP, even though they considered themselves in good health. These findings can aid with coordinated efforts from government and health professionals to help manage and promote the prevention of LBP by considering the older adult population's needs in the state of Amazonas.

Genomics, epigenomics and pharmacogenomics of familial hypercholesterolemia (FHBGEP): A study protocol.

BACKGROUND: Familial hypercholesterolemia (FH) is a genetic disease that affects millions of people worldwide. OBJECTIVES: The study protocol FHBGEP was design to investigate the main genomic, epigenomic, and pharmacogenomic factors associated with FH and polygenic hypercholesterolemia (PH). METHODS: FH patients will be enrolled at six research centers in Brazil. An exon-targeted gene strategy will be used to sequence a panel of 84 genes related to FH, PH, pharmacogenomics and coronary artery disease. Variants in coding and regulatory regions will be identified using a proposed variant discovery pipeline and classified according to the American College Medical Genetics guidelines. Functional effects of variants in FH-related genes will be investigated by in vitro studies using lymphocytes and cell lines (HepG2, HUVEC and HEK293FT), CRISPR/Cas9 mutagenesis, luciferase reporter assay and other technologies. Functional studies in silico, such as molecular docking, molecular dynamics, and conformational analysis, will be used to explore the impact of novel variants on protein structure and function. DNA methylation profile and differential expression of circulating non-coding RNAs (miRNAs and lncRNAs) will be analyzed in FH patients and normolipidemic subjects (control group). The influence of genomic and epigenomic factors on metabolic and inflammatory status will be analyzed in FH patients. Pharmacogenomic studies will be conducted to investigate the influence of genomic and epigenomic factors on response to statins in FH patients. SUMMARY: The FHBGEP protocol has the potential to elucidate the genetic basis and molecular mechanisms involved in the pathophysiology of FH and PH, particularly in the Brazilian population. This pioneering approach includes genomic, epigenomic and functional studies, which results will contribute to the improvement of the diagnosis, prognosis and personalized therapy of FH patients.

Risk factors for oropharyngeal dysphagia in cardiovascular diseases.

Some conditions consolidated as risk factors for oropharyngeal dysphagia have already been identified in other diseases, such as neurological. Studies on cardiovascular diseases concentrate in individuals in the postoperative period; thus, it is unknown if these same factors occur in individuals hospitalized for clinical or surgical treatment of these diseases. Objective to correlate predictive risk factors for oropharyngeal dysphagia in individuals with cardiovascular disease admitted at a reference cardiology hospital. Methodology This is a retrospective clinical study. Medical records of 175 individuals hospitalized for clinical and/or surgical treatment at a reference cardiology hospital from January to June 2017, attendants of the Speech-Language Pathology and Nutrition team, were analyzed. Of these, 100 records were included in the study: 41 females and 59 males (mean age 67.56 years). Deaths and individuals from 0 to 18 years were excluded. Stroke, malnutrition, age and prolonged orotracheal intubation were considered predictive risk factors for oropharyngeal dysphagia. Mann-Whitney test and Fisher's test were used for statistical analysis. Results Stroke (OR=2.93 p=0.02), malnutrition (OR=2.89 p=0.02) and prolonged orotracheal intubation (OR=3.94 p=0.02) were statistically significant predictors for oropharyngeal dysphagia within this population. Age below 80 years was not significant (p=0.06), but within octogenarians, significance was found (p=0.033). Conclusion Stroke, malnutrition, prolonged orotracheal intubation and age > 80 years are predictive risk factors for oropharyngeal dysphagia in adult population with cardiovascular diseases.

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.

Increased levels of plasma IL-1b and BDNF can predict resistant depression patients.

BACKGROUND: There is no strong evidence on the link between inflammatory profile and pattern of drug treatment response in depressive patients that could result in Coronary Artery Disease occurrence. OBJECTIVE: This study aimed to compare the subclinical atherosclerosis markers, inflammatory profile, and BDNF production in Resistant Depression (RD) or Bipolar Affective Disorder (BAD) patients under conventional treatment. METHODS: The population evaluated was comprised of 34 RD, 43 BAD, and 41 controls. Subclinical atherosclerosis markers were evaluated using ultrasonography, tomography, and exercise stress test. Plasma concentrations of TNFα, IL-1ß, IL-6, and BDNF were measured using Luminex100™. The usCRP concentration was measured using turbidimetric immunoassay. IL1B, IL6, and TNFA expression were determined using TaqMan®. For the statistical analysis, the significance level was established at p<0.05. RESULTS: Concerning subclinical atherosclerosis markers, only O2 consumption was reduced in the BAD group (p = 0.001). Although no differences were found in gene expression, BDNF and IL-1ß plasma concentration was increased in the RD group (p = 0.002 and p = 0.005, respectively) even with an antidepressant treatment, which suggests that these drugs have no effect in IL-1ß secretion and that the inflammasome may play a role in therapy response. CONCLUSION: Taken together, both BDNF and IL-1ß plasma concentrations could be used to the early identification of RD patients.

Use of Quality of Life in Cardiovascular Surgery in Coronary Artery Bypass Grafting: Validation, Reproducibility, and Quality of Life in One Year of Follow-Up.

BACKGROUND: The objectives of this study are to validate the Quality of Life in Cardiovascular Surgery (QLCS) questionnaire and to observe the evolution of quality of life in the first year of postoperative follow-up of patients who underwent coronary artery bypass grafting (CABG). METHODS: This was a prospective observational study of patients undergoing CABG from July 2016 to June 2017 who survived and answered the QLCS with 1, 6, and 12 months of follow-up. Validation was evaluated for internal consistency by Cronbach's alpha, test-retest reproducibility by correlation coefficient of concordance, and accuracy for interrater reliability by the kappa statistic. The nonparametric analysis of variance test was used for analysis of repeated measures, during follow-up, of the QLCS was considered significant at p < 0.05. RESULTS: Included were 360 patients, with a mean age of 63 years; 72% were men. Cronbach's alpha was 0.82, demonstrating adequate internal consistency. The correlation coefficient of concordance was 0.93 and accuracy 0.99, showing good precision and accuracy. The kappa statistic for questions ranged from 0.58 to 0.78, which ensures a moderate reproducibility. Scores of the QLCS in patients undergoing CABG of 17.69, 18.82, and 19.52 were found at 1, 6, and 12 months, respectively. Thus there was a progressive improvement in quality of life over the first year of follow-up (p < 0.0001). CONCLUSIONS: The QLCS proved to be a good questionnaire in this population, with adequate internal consistency and moderate reproducibility. Its use revealed a progressive and significant improvement in the quality of life of patients undergoing CABG.

Effectiveness of CoronaVac in the prevention of COVID-19, a test-negative case-control study in Brazil

The present study aimed to evaluate the effectiveness of two doses of CoronaVac in preventing SARS-CoV-2 symptomatic disease with virological confirmation, as well as in the prevention of COVID-19 moderate and severe cases. A test-negative unmatched case-control design was used, in which cases were patients with suspected COVID-19 (presenting at least two of the following symptoms: fever, chills, sore throat, headache, cough, runny nose, olfactory or taste disorders) with virological confirmation, and controls were those whose SARS-CoV-2 test was negative. As for exposure, participants were classified as unvaccinated, or vaccinated with a complete schedule. Suspected COVID-19 cases were identified from March to November 2021, in two cities located in the State of Sao Paulo, Brazil. All participa ~ nts signed the Informed Consent Form before enrollment. RT-PCR results and vaccination data were obtained from the local surveillance systems. Up to two phone calls were made to obtain information on the outcome of the cases. A total of 2981 potential participants were screened for eligibility, of which 2163 were included, being 493 cases and 1670 controls. Vaccination, age, the reported contact with a COVID-19 suspected or confirmed case in the 14 days before symptoms onset, and the educational level were the variables independently associated with the outcome. The adjusted vaccine effectiveness for symptomatic COVID-19 (AVE) was 39.0 % (95 % CI 6.0−60.0 %). The AVE in the prevention of moderate and severe disease was 91.0 % (95 % CI 76.0−97.0 %). Our results were influenced by the waning of the Gamma variant, in the second trimester of 2021, followed by the increase in vaccination coverage, and a drop in the number of cases in the second half of the year. The study demonstrated the high effectiveness of CoronaVac in preventing moderate/severe COVID-19 cases.

Effectiveness of coronavac in the prevention of COVID-19, a test-negative case-control study in Brazil

The present study aimed to evaluate the effectiveness of two doses of CoronaVac in preventing SARS-CoV-2 symptomatic disease with virological confirmation, as well as in the prevention of COVID-19 moderate and severe cases. A test-negative unmatched case-control design was used, in which cases were patients with suspected COVID-19 (presenting at least two of the fol lowing symptoms: fever, chills, sore throat, headache, cough, runny nose, olfactory or taste dis orders) with virological confirmation, and controls were those whose SARS-CoV-2 test was negative. As for exposure, participants were classified as unvaccinated, or vaccinated with a complete schedule. Suspected COVID-19 cases were identified from March to November 2021, in two cities located in the State of Sao Paulo, Brazil. All participa ~ nts signed the Informed Con sent Form before enrollment. RT-PCR results and vaccination data were obtained from the local surveillance systems. Up to two phone calls were made to obtain information on the out come of the cases. A total of 2981 potential participants were screened for eligibility, of which 2163 were included, being 493 cases and 1670 controls. Vaccination, age, the reported contact with a COVID-19 suspected or confirmed case in the 14 days before symptoms onset, and the educational level were the variables independently associated with the outcome. The adjusted vaccine effectiveness for symptomatic COVID-19 (AVE) was 39.0 % (95 % CI 6.0−60.0 %). The AVE in the prevention of moderate and severe disease was 91.0 % (95 % CI 76.0−97.0 %). Our results were influenced by the waning of the Gamma variant, in the second trimester of 2021, followed by the increase in vaccination coverage, and a drop in the number of cases in the sec ond half of the year. The study demonstrated the high effectiveness of CoronaVac in prevent ing moderate/severe COVID-19 cases.

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.

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.