Efficacy of the adjuvanted subunit protein COVID-19 vaccine, SCB-2019: a phase 2 and 3 multicentre, double-blind, randomised, placebo-controlled trial.

BACKGROUND: A range of safe and effective vaccines against SARS CoV 2 are needed to address the COVID 19 pandemic. We aimed to assess the safety and efficacy of the COVID-19 vaccine SCB-2019. METHODS: This ongoing phase 2 and 3 double-blind, placebo-controlled trial was done in adults aged 18 years and older who were in good health or with a stable chronic health condition, at 31 sites in five countries (Belgium, Brazil, Colombia, Philippines, and South Africa). The participants were randomly assigned 1:1 using a centralised internet randomisation system to receive two 0·5 mL intramuscular doses of SCB-2019 (30 µg, adjuvanted with 1·50 mg CpG-1018 and 0·75 mg alum) or placebo (0·9% sodium chloride for injection supplied in 10 mL ampoules) 21 days apart. All study staff and participants were masked, but vaccine administrators were not. Primary endpoints were vaccine efficacy, measured by RT-PCR-confirmed COVID-19 of any severity with onset from 14 days after the second dose in baseline SARS-CoV-2 seronegative participants (the per-protocol population), and the safety and solicited local and systemic adverse events in the phase 2 subset. This study is registered on EudraCT (2020-004272-17) and ClinicalTrials.gov (NCT04672395). FINDINGS: 30 174 participants were enrolled from March 24, 2021, until the cutoff date of Aug 10, 2021, of whom 30 128 received their first assigned vaccine (n=15 064) or a placebo injection (n=15 064). The per-protocol population consisted of 12 355 baseline SARS-CoV-2-naive participants (6251 vaccinees and 6104 placebo recipients). Most exclusions (13 389 [44·4%]) were because of seropositivity at baseline. There were 207 confirmed per-protocol cases of COVID-19 at 14 days after the second dose, 52 vaccinees versus 155 placebo recipients, and an overall vaccine efficacy against any severity COVID-19 of 67·2% (95·72% CI 54·3-76·8), 83·7% (97·86% CI 55·9-95·4) against moderate-to-severe COVID-19, and 100% (97·86% CI 25·3-100·0) against severe COVID-19. All COVID-19 cases were due to virus variants; vaccine efficacy against any severity COVID-19 due to the three predominant variants was 78·7% (95% CI 57·3-90·4) for delta, 91·8% (44·9-99·8) for gamma, and 58·6% (13·3-81·5) for mu. No safety issues emerged in the follow-up period for the efficacy analysis (median of 82 days [IQR 63-103]). The vaccine elicited higher rates of mainly mild-to-moderate injection site pain than the placebo after the first (35·7% [287 of 803] vs 10·3% [81 of 786]) and second (26·9% [189 of 702] vs 7·4% [52 of 699]) doses, but the rates of other solicited local and systemic adverse events were similar between the groups. INTERPRETATION: Two doses of SCB-2019 vaccine plus CpG and alum provides notable protection against the entire severity spectrum of COVID-19 caused by circulating SAR-CoV-2 viruses, including the predominating delta variant. FUNDING: Clover Biopharmaceuticals and the Coalition for Epidemic Preparedness Innovations.

Immunogenicity and safety of beta variant COVID-19 vaccine AZD2816 and AZD1222 (ChAdOx1 nCoV-19) as primary-series vaccination for previously unvaccinated adults in Brazil, South Africa, Poland, and the UK: a randomised, partly double-blinded, phase 2/3 non-inferiority immunobridging study.

BACKGROUND: AZD2816 is a variant-adapted COVID-19 vaccine that expresses the full-length SARS-CoV-2 beta variant spike protein but is otherwise similar to AZD1222 (ChAdOx1 nCoV-19). This study aimed to evaluate the safety and immunogenicity of AZD1222 or AZD2816 (or both) primary-series vaccination in a cohort of adult participants who were previously unvaccinated. METHODS: In this phase 2/3, randomised, multinational, active-controlled, non-inferiority, immunobridging study, adult participants previously unvaccinated for COVID-19 were enrolled at 16 study sites in Brazil, South Africa, Poland, and the UK. Participants were stratified by age, sex, and comorbidity and randomly assigned 5:5:5:2 to receive a primary series of AZD1222 (AZD1222 group), AZD2816 (AZD2816 [4-week] group), or AZD1222-AZD2816 (AZD1222-AZD2816 group) at 4-week dosing intervals, or AZD2816 at a 12-week interval (AZD2816 [12-week] group) and evaluated for safety and immunogenicity through 180 days after dose 2. Primary outcomes were safety (rates of solicited adverse events occurring during 7 days and unsolicited adverse events occurring during 28 days after each dose) and immunogenicity (non-inferiority of pseudovirus neutralising antibody geometric mean titre [GMT], GMT ratio margin of 0·67, and seroresponse rate, rate difference margin of -10%, recorded 28 days after dose 2 with AZD2816 [4-week interval] against beta vs AZD1222 against ancestral SARS-CoV-2) in participants who were seronegative at baseline. This trial is registered with ClinicalTrials.gov, NCT04973449, and is completed. FINDINGS: Between July 7 and Nov 12, 2021, 1449 participants were assigned to the AZD1222 group (n=413), the AZD2816 (4-week) group (n=415), the AZD1222-AZD2816 group (n=412), and the AZD2816 (12-week) group (n=209). Ten (2·6%) of 378 participants who were seronegative at baseline in the AZD1222 group, nine (2·4%) of 379 in the AZD2816 (4-week) group, eight (2·1%) of 380 in the AZD1222-AZD2816 group, and 11 (5·8%) of 191 in the AZD2816 (12-week) group had vaccine-related unsolicited adverse events. Serious adverse events were recorded in one (0·3%) participant in the AZD1222 group, one (0·3%) in the AZD2816 (4-week) group, two (0·5%) in the AZD1222-AZD2816 group, and none in the AZD2816 (12-week) group. Co-primary immunogenicity endpoints were met: neutralising antibody GMT (ratio 1·19 [95% CI 1·08-1·32]; lower bound greater than 0·67) and seroresponse rate (difference 1·7% [-3·1 to 6·5]; lower bound greater than -10%) at 28 days after dose 2 were non-inferior in the AZD2816 (4-week) group against beta versus in the AZD1222 group against ancestral SARS-CoV-2. Seroresponse rates were highest with AZD2816 against beta (12-week interval 94·3% [95% CI 89·4-97·3]; 4-week interval 85·7% [81·5-89·2]) and with AZD1222 (84·6% [80·3-88·2]) against ancestral SARS-CoV-2. INTERPRETATION: Primary series of AZD1222 and AZD2816 were well tolerated, with no emergent safety concerns. Both vaccines elicited robust immunogenicity against beta and ancestral SARS-CoV-2 with greater responses demonstrated when testing against SARS-CoV-2 strains that matched those targeted by the respective vaccine. These findings demonstrate the continued importance of ancestral COVID-19 vaccines in protecting against severe COVID-19 and highlight the feasibility of using the ChAdOx1 platform to develop COVID-19 vaccines against future SARS-CoV-2 variants. FUNDING: AstraZeneca.

Primary results of the brazilian registry of atherothrombotic disease (NEAT).

There is limited contemporary prospective real-world evidence of patients with chronic arterial disease in Latin America. The Network to control atherothrombosis (NEAT) registry is a national prospective observational study of patients with known coronary (CAD) and/or peripheral arterial disease (PAD) in Brazil. A total of 2,005 patients were enrolled among 25 sites from September 2020 to March 2022. Patient characteristics, medications and laboratorial data were collected. Primary objective was to assess the proportion of patients who, at the initial visit, were in accordance with good medical practices (domains) for reducing cardiovascular risk in atherothrombotic disease. From the total of patients enrolled, 2 were excluded since they did not meet eligibility criteria. Among the 2,003 subjects included in the analysis, 55.6% had isolated CAD, 28.7% exclusive PAD and 15.7% had both diagnoses. Overall mean age was 66.3 (± 10.5) years and 65.7% were male patients. Regarding evidence-based therapies (EBTs), 4% were not using any antithrombotic drug and only 1.5% were using vascular dose of rivaroxaban (2.5 mg bid). Only 0.3% of the patients satisfied all the domains of secondary prevention, including prescription of EBTs and targets of body-mass index, blood pressure, LDL-cholesterol, and adherence of lifestyle recommendations. The main barrier for prescription of EBTs was medical judgement. Our findings highlight that the contemporary practice does not reflect a comprehensive approach for secondary prevention and had very low incorporation of new therapies in Brazil. Large-scale populational interventions addressing these gaps are warranted to improve the use of evidence-based therapies and reduce the burden of atherothrombotic disease.ClinicalTrials.gov NCT04677725.

Brazilian Registry of Interventional Cardiology during the COVID-19 Pandemic (RBCI-COVID19). / Registro Brasileiro de Cardiologia Intervencionista durante a Pandemia de COVID-19 (RBCI-COVID19).

BACKGROUND: At the beginning of the COVID-19 pandemic, patients with myocardial infarction (MI) took longer to present to hospitals because of fear of contamination and health care access difficulties. OBJECTIVES: To assess interventional cardiology procedures performed during the COVID-19 pandemic and its implications for MI approach. METHODS: Prospective registry of 24 cardiac catheterization laboratories in Brazil, with adult patients undergoing interventional cardiology procedures between May 26 and November 30, 2020. The outcomes were cardiovascular (CV) and non-CV complications, death, and MI. Concomitant COVID-19 was confirmed using RT-PCR. Machine learning techniques were used with nonparametric Classification Trees models, and Simple Correspondence Analysis, with R statistical software package. Significance level adopted of 5%. RESULTS: This study included 1282 patients, 435 of whom (33.9%) had MI as follows: ST-segment elevation MI (STEMI), 239 (54.9%); and non-ST-segment elevation MI (NSTEMI), 196 (45.1%). Of the 1282 patients, 29 had CV complications, 47 had non-CV complications, and 31 died. The diagnosis of COVID-19 was confirmed in 77 patients (6%), with 15.58% mortality and non-CV complications in 6.49%. Most patients had significant coronary artery disease (63%), and an intracoronary thrombus was more often found in the presence of STEMI (3.4%) and COVID-19 (4%). A door-to-table time longer than 12 hours in NSTEMI was associated with 30.8% of complications, 25% in COVID-19 patients. CONCLUSIONS: All deaths were preceded by CV or non-CV complications. The presence of COVID-19 was associated with death and non-fatal complications of patients undergoing interventional cardiology procedures during the pandemic.

FUNDAMENTO: No início da pandemia de COVID-19, os pacientes com infarto do miocárdio (IM) demoraram para procurar um hospital por medo de contágio ou dificuldades no acesso aos serviços de saúde. OBJETIVOS: Avaliar procedimentos de cardiologia intervencionista realizados durante a pandemia de COVID-19 e implicações na abordagem do IM. MÉTODOS: Registro prospectivo de 24 centros de hemodinâmica no Brasil, com pacientes adultos submetidos a procedimentos de cardiologia intervencionista entre 26 de maio e 30 de novembro de 2020. Os desfechos foram complicações cardiovasculares (CV) e não CV, morte e IM. A concomitância de COVID-19 foi confirmada com RT-PCR. Técnicas de machine learning foram usadas com modelos não paramétricos de árvores de classificação. Usou-se análise de correspondência simples com o software R. Adotou-se nível de significância de 5%. RESULTADOS: Este estudo incluiu 1.282 pacientes, 435 dos quais (33,9%) apresentaram IM: IM com supra de ST (IMCSST), 239 (54,9%); e IM sem supra de ST(IMSSST), 196 (45.1%). Dos 1.282 pacientes, 29 tiveram complicações CV, 47 tiveram complicações não CV e 31 morreram. O diagnóstico de COVID-19 foi confirmado em 77 pacientes (6%), com 15,58% de mortalidade e 6,49% de complicações não CV. A maioria dos pacientes apresentou significativa doença arterial coronariana (63%). Trombo intracoronariano foi mais frequente na presença de IMCSST (3,4%) e COVID-19 (4%). Tempo porta-mesa superior a 12 horas no IMSSST associou-se a 30,8% de complicações, 25% em pacientes com COVID-19. CONCLUSÕES: Todos os óbitos foram precedidos por complicações CV ou não CV. A presença de COVID-19 foi associada a óbito e complicações não fatais dos pacientes submetidos a procedimentos de cardiologia intervencionista durante a pandemia.

Women Physicians: Burnout during the COVID-19 Pandemic in Brazil. / Mulheres Médicas: Burnout durante a Pandemia de COVID-19 no Brasil.

BACKGROUND: COVID-19 has placed a tremendous burden on physicians worldwide, especially women physicians, affected by increased workload and loss of quality of life. OBJECTIVE: To assess the effects of the COVID-19 pandemic on the quality of life, burnout and spirituality of Brazilian women physicians directly or indirectly providing care to COVID-19 patients. METHODS: Prospective, observational study performed from July 28 to September 27, 2020, in Brazil, with women physicians from 47 specialities, the most frequent being cardiology (22.8%), with no age restriction. They voluntarily answered an online survey with questions on demographic and socioeconomic characteristics, quality of life (WHOQOL-brief), spirituality (WHOQOL-SRPB), and statements from the Oldenburg Burnout Inventory. Statistical analysis used the R software, beta regression, classification trees, and polychoric correlation matrix, with a 5% of significance level. RESULTS: Of the 769 respondents, 61.6% reported signs of burnout. About 64% reported wage loss of up to 50% during the pandemic. Some reported lack of energy for daily tasks, frequent negative feelings, dissatisfaction with capability for work, and caring for others not adding meaning to their lives. Negative feelings correlated negatively with satisfaction with sexual life and personal relations, and energy for daily tasks. The inability to remain optimistic in times of uncertainty correlated positively with feeling unsafe daily and not acknowledging that caring for others brings meaning to life. CONCLUSION: This study showed a high frequency of burnout among Brazilian women physicians who answered the survey during the COVID-19 pandemic. Nevertheless, they presented with a relatively good quality of life and believed that spirituality comforted and reassured them in hard times.

FUNDAMENTO: A COVID-19 adicionou um fardo enorme sobre os médicos ao redor do mundo, especialmente as mulheres médicas, que são afetadas pelo aumento da carga de trabalho e pela perda da qualidade de vida. OBJETIVO: Avaliar os efeitos da pandemia de COVID-19 na qualidade de vida, burnout e espiritualidade de médicas brasileiras que atendem pacientes com COVID-19 direta ou indiretamente. MÉTODO: Estudo prospectivo, observacional realizado de 28 de julho a 27 de setembro de 2020, no Brasil, com mulheres médicas de 47 especialidades, a mais frequente sendo a cardiologia (22,8%), sem restrição de idade. Elas responderam voluntariamente um questionário online com questões sobre características demográficas e socioeconômicas, qualidade de vida (WHOQOL-brief) e espiritualidade (WHOQOL-SRPB) e enunciados do Oldenburg Burnout Inventory. A análise estatística utilizou o software R, regressão beta, árvores de classificação e matriz de correlação policórica, com nível de significância de 5%. RESULTADOS: Das 769 respondentes, 61,6% relataram sinais de burnout. Cerca de 64% relataram perda salarial de até 50% durante a pandemia. Algumas relataram falta de energia para as tarefas diárias, sentimentos negativos frequentes, insatisfação com a capacidade para o trabalho, e que cuidar de outras pessoas não agregava sentido às suas vidas. Os sentimentos negativos correlacionaram-se negativamente com a satisfação com a vida sexual, a satisfação com as relações pessoais e a energia para as tarefas diárias. A incapacidade de permanecer otimista em tempos de incerteza correlacionou-se positivamente com a sensação de insegurança no dia a dia e com o não reconhecimento de que cuidar de outras pessoas trouxesse sentido à vida. CONCLUSÃO: O presente estudo mostrou uma alta frequência de burnout entre as médicas brasileiras que responderam ao questionário durante a pandemia de COVID-19. Apesar disso, apresentavam uma qualidade de vida relativamente boa e acreditavam que a espiritualidade trazia-lhes conforto e segurança nos momentos difíceis.

TREML4 mRNA Expression and Polymorphisms in Blood Leukocytes are Associated with Atherosclerotic Lesion Extension in Coronary Artery Disease.

Members of the triggering receptor expressed on myeloid cells (TREM) family are associated with atherosclerosis risk and progression. TREML4 is upregulated in the early phase of acute coronary syndrome. We investigated the relationship between the mRNA expression of 13 genes in blood leukocytes, TREML4 polymorphisms, and coronary artery lesion extension (Friesinger index) in patients with coronary artery disease (CAD) (n = 137). TREML4 rs2803495 (A > G) and rs2803496 (T > C) variants and leukocyte mRNA expression were analysed by qRT-PCR. TREML4 expression was higher in patients with major coronary artery lesions than in subjects without or with low and intermediate lesions (p < 0.05). However, TREML4 polymorphisms were not associated with coronary lesion extent. Presence of the rs2803495 G allele was not associated with increased TREML4 mRNA expression. Patients carrying the rs2803496 C allele (TC/CC genotypes) were more likely to express TREML4 mRNA than non-C allele carriers (allele C: OR 7.3, and 95% CI 1.9-27.5, p = 0.03). In conclusion, increased TREML4 mRNA expression in blood leukocytes is influenced by gene polymorphisms and is associated with more severe coronary artery lesions, suggesting its potential as a biomarker of the extent of coronary lesions in patients with CAD.

Differences in the inflammatory response between patients with and those without diabetes mellitus after coronary stenting.

BACKGROUND: Patients with diabetes mellitus who undergo coronary stenting are at increased risk of restenosis. It is known that inflammation plays a crucial role in restenosis. OBJECTIVE: We assessed the inflammatory response to elective coronary stent implantation (CSI) in stable diabetic and nondiabetic patients. METHODS: C-reactive protein (CRP), soluble (s) P-selectin, and soluble intercellular adhesion molecule (sICAM)-1 plasma levels were determined in diabetic (n = 51) and nondiabetic (n = 56) patients before and 48 hours and 4 weeks after bare metal stenting (BMS). RESULTS: Diabetic patients presented significantly higher inflammatory marker levels before and after CSI. Nonetheless, diabetic and nondiabetic patients had postintervention peak of markers attained within 48 hours. At baseline, diabetic and nondiabetic patients presented CRP levels of 5.0 +/- 20.1 (P < or = 0.04) and 3.8 +/- 9.4 microg/ml and, at 48 hours postintervention, 22.0 +/- 20.2 (P = 0.001; P = 0.002) and 12.6 +/- 11.3 (P < or = 0.0001) microg/ml. Regarding sP-selectin, diabetic and nondiabetic patients obtained levels of, at baseline, 182 +/- 118 (P < or = 0.04) and 105 +/- 48 ng/ml and, at 48 hours, 455 +/- 290 (P = 0.001; P < or = 0.01) and 215 +/- 120 (P < or = 0.04) ng/ml. For diabetic and nondiabetic patients, sICAM-1 levels were, at baseline, 248 +/- 98 (P < or = 0.04) and 199 +/- 94 ng/ml and, at 48 hours, 601 +/- 201 (P = 0.001; P < or = 0.01) and 283 +/- 220 (P = 0.001) ng/ml. At 4 weeks, for all patients, markers returned to preprocedural levels: versus before PCI: *P = 0.001, (section sign)P < or = 0.0001; versus nondiabetic patients: (#)P < or = 0.04, (paragraph sign)P = 0.002, (Upsilon)P < or = 0.01. CONCLUSIONS: Diabetic and nondiabetic patients exhibited a temporal inflammatory response after an elective BMS. However, diabetic patients present higher preprocedural levels of CRP, sP-selectin, and sICAM-1 and reveal a further exacerbated inflammatory response after intervention. The differences in inflammatory response may have implications in restenosis within these two sets of patients.

Degenerative Aortic Stenosis in Women: Challenges and Perspectives

Abstract Degenerative aortic stenosis is currently a public health problem. Affecting the elderly population, this pathology has been showing an increasing prevalence as a direct result of the population aging. In this context, women have a greater life expectancy, corresponding to most of the population with degenerative aortic stenosis. Specific characteristics of this pathology in females are present in the diagnosis, pathophysiology, anatomical aspects, imaging and in therapeutic approach. Women present a more severe disease with less valve calcification than men, more concentric ventricular remodeling, higher transvalvular gradients, and less myocardial fibrosis. Less evident symptoms mean that these patients are referred later for surgical or percutaneous therapeutic treatment. The greater comorbidity presented by females and possibly due to the smaller body surface, bring specific aspects that affect the surgery results, leading to higher mortality rates and, more often, the prosthesis-patient mismatch. Percutaneous valve implantation is a good alternative, with better results in females, when compared to surgery, both in the treatment of native valves and in the treatment of a previously implanted bioprosthesis' dysfunction. The challenges encountered for the treatment of aortic stenosis in women and their possible solutions are described in this article, focusing on the observed difference of aortic stenosis in females and their possible solutions.

Registro Brasileiro de Cardiologia Intervencionista durante a Pandemia de COVID-19 (RBCI-COVID19) / Brazilian Registry of Interventional Cardiology during the COVID-19 Pandemic (RBCI-COVID19)

Resumo Fundamento No início da pandemia de COVID-19, os pacientes com infarto do miocárdio (IM) demoraram para procurar um hospital por medo de contágio ou dificuldades no acesso aos serviços de saúde. Objetivos Avaliar procedimentos de cardiologia intervencionista realizados durante a pandemia de COVID-19 e implicações na abordagem do IM. Métodos Registro prospectivo de 24 centros de hemodinâmica no Brasil, com pacientes adultos submetidos a procedimentos de cardiologia intervencionista entre 26 de maio e 30 de novembro de 2020. Os desfechos foram complicações cardiovasculares (CV) e não CV, morte e IM. A concomitância de COVID-19 foi confirmada com RT-PCR. Técnicas de machine learning foram usadas com modelos não paramétricos de árvores de classificação. Usou-se análise de correspondência simples com o software R. Adotou-se nível de significância de 5%. Resultados Este estudo incluiu 1.282 pacientes, 435 dos quais (33,9%) apresentaram IM: IM com supra de ST (IMCSST), 239 (54,9%); e IM sem supra de ST(IMSSST), 196 (45.1%). Dos 1.282 pacientes, 29 tiveram complicações CV, 47 tiveram complicações não CV e 31 morreram. O diagnóstico de COVID-19 foi confirmado em 77 pacientes (6%), com 15,58% de mortalidade e 6,49% de complicações não CV. A maioria dos pacientes apresentou significativa doença arterial coronariana (63%). Trombo intracoronariano foi mais frequente na presença de IMCSST (3,4%) e COVID-19 (4%). Tempo porta-mesa superior a 12 horas no IMSSST associou-se a 30,8% de complicações, 25% em pacientes com COVID-19. Conclusões Todos os óbitos foram precedidos por complicações CV ou não CV. A presença de COVID-19 foi associada a óbito e complicações não fatais dos pacientes submetidos a procedimentos de cardiologia intervencionista durante a pandemia.

Abstract Background At the beginning of the COVID-19 pandemic, patients with myocardial infarction (MI) took longer to present to hospitals because of fear of contamination and health care access difficulties. Objectives To assess interventional cardiology procedures performed during the COVID-19 pandemic and its implications for MI approach. Methods Prospective registry of 24 cardiac catheterization laboratories in Brazil, with adult patients undergoing interventional cardiology procedures between May 26 and November 30, 2020. The outcomes were cardiovascular (CV) and non-CV complications, death, and MI. Concomitant COVID-19 was confirmed using RT-PCR. Machine learning techniques were used with nonparametric Classification Trees models, and Simple Correspondence Analysis, with R statistical software package. Significance level adopted of 5%. Results This study included 1282 patients, 435 of whom (33.9%) had MI as follows: ST-segment elevation MI (STEMI), 239 (54.9%); and non-ST-segment elevation MI (NSTEMI), 196 (45.1%). Of the 1282 patients, 29 had CV complications, 47 had non-CV complications, and 31 died. The diagnosis of COVID-19 was confirmed in 77 patients (6%), with 15.58% mortality and non-CV complications in 6.49%. Most patients had significant coronary artery disease (63%), and an intracoronary thrombus was more often found in the presence of STEMI (3.4%) and COVID-19 (4%). A door-to-table time longer than 12 hours in NSTEMI was associated with 30.8% of complications, 25% in COVID-19 patients. Conclusions All deaths were preceded by CV or non-CV complications. The presence of COVID-19 was associated with death and non-fatal complications of patients undergoing interventional cardiology procedures during the pandemic.

Relationship between circulating VCAM-1, ICAM-1, E-selectin and MMP9 and the extent of coronary lesions.

OBJECTIVES: Inflammatory molecules play a role in the development of atherosclerosis, which is the primary origin of cardiovascular disorders. However, to the best of our knowledge, no study has attempted to investigate the relationship between these circulating molecules and the prediction of cardiovascular risk. The present study aimed to investigate the relationships of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin and matrix metalloproteinase 9 serum concentrations with the extent of coronary lesions. METHODS: Seventy-four individuals who were undergoing coronary angiography for the first time for diagnostic purposes were enrolled in this study. The extent of the coronary lesion was assessed using the Friesinger Index, and subjects were classified into four groups: no lesions, minor lesions, intermediate lesions and major lesions. Serum biochemical parameters and serum concentrations of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin and matrix metalloproteinase 9 were analyzed. RESULTS: The vascular cell adhesion molecule-1 concentration was higher than 876 ng/mL in individuals with intermediate and major lesions (p<0.001 and p=0.020, respectively). Moreover, logistic regression analysis showed that these patients had an increased risk of having an intermediate lesion (p=0.007). Interestingly, all individuals with major lesions had vascular cell adhesion molecule-1 concentrations higher than 876 ng/mL. No association was found between the concentrations of the other proteins and the Friesinger Index. CONCLUSIONS: Serum vascular cell adhesion molecule-1 may be associated with the extent of coronary lesions. Moreover, it may represent an alternative to improve the cardiovascular risk classification in patients without acute coronary syndrome.

Association of Serum Alpha-Tocopherol and Retinol with the Extent of Coronary Lesions in Coronary Artery Disease.

Background and aims: Fat-soluble vitamins play an important role in the pathogenesis of cardiovascular disease and progression of atherosclerosis. This study aimed at investigating the relationship of the serum levels of alpha-tocopherol and retinol with the extent of coronary lesions in patients with coronary artery disease. Methods. Patients with coronary artery disease (n=177) aged 30-74 years, who underwent their first coronary angiography, were enrolled. The extent of coronary lesions was assessed using the Friesinger index (FI). Accordingly, patients were grouped as follows: FI = 0-4 (n=90), FI = 5-9 (n=50), and FI = 10-15 (n=37). Serum levels of vitamins were ‬determined via high-performance liquid chromatography and serum biochemical analysis. Results. Assessment of FI-based groups revealed that 50.8% patients had a coronary artery lesion to a low extent (FI 0-4). Individuals in this group were younger and had lower glucose and serum alpha-tocopherol levels than the other groups (p < 0.05). Low levels of alpha-tocopherol were more frequent in the FI 0-4 group than that in the other groups (p=0.03). No difference was observed between the mean serum retinol levels among the FI-based groups (n=0.492), and the low frequency of retinol was consistent among the FI groups (n=0.348). Conclusions. The low level of alpha-tocopherol together with the presence of dyslipidemia is probably associated with the initial events in atherosclerosis. Increased alpha-tocopherol levels in patients with more extensive coronary artery lesions may have resulted from altered vitamin E metabolism with increased oxidative stress.

Mulheres Médicas: Burnout durante a Pandemia de COVID-19 no Brasil / Women Physicians: Burnout during the COVID-19 Pandemic in Brazil

Resumo Fundamento A COVID-19 adicionou um fardo enorme sobre os médicos ao redor do mundo, especialmente as mulheres médicas, que são afetadas pelo aumento da carga de trabalho e pela perda da qualidade de vida. Objetivo Avaliar os efeitos da pandemia de COVID-19 na qualidade de vida, burnout e espiritualidade de médicas brasileiras que atendem pacientes com COVID-19 direta ou indiretamente. Método Estudo prospectivo, observacional realizado de 28 de julho a 27 de setembro de 2020, no Brasil, com mulheres médicas de 47 especialidades, a mais frequente sendo a cardiologia (22,8%), sem restrição de idade. Elas responderam voluntariamente um questionário online com questões sobre características demográficas e socioeconômicas, qualidade de vida (WHOQOL-brief) e espiritualidade (WHOQOL-SRPB) e enunciados do Oldenburg Burnout Inventory. A análise estatística utilizou o software R, regressão beta, árvores de classificação e matriz de correlação policórica, com nível de significância de 5%. Resultados Das 769 respondentes, 61,6% relataram sinais de burnout. Cerca de 64% relataram perda salarial de até 50% durante a pandemia. Algumas relataram falta de energia para as tarefas diárias, sentimentos negativos frequentes, insatisfação com a capacidade para o trabalho, e que cuidar de outras pessoas não agregava sentido às suas vidas. Os sentimentos negativos correlacionaram-se negativamente com a satisfação com a vida sexual, a satisfação com as relações pessoais e a energia para as tarefas diárias. A incapacidade de permanecer otimista em tempos de incerteza correlacionou-se positivamente com a sensação de insegurança no dia a dia e com o não reconhecimento de que cuidar de outras pessoas trouxesse sentido à vida. Conclusão O presente estudo mostrou uma alta frequência de burnout entre as médicas brasileiras que responderam ao questionário durante a pandemia de COVID-19. Apesar disso, apresentavam uma qualidade de vida relativamente boa e acreditavam que a espiritualidade trazia-lhes conforto e segurança nos momentos difíceis.

Abstract Background COVID-19 has placed a tremendous burden on physicians worldwide, especially women physicians, affected by increased workload and loss of quality of life. Objective To assess the effects of the COVID-19 pandemic on the quality of life, burnout and spirituality of Brazilian women physicians directly or indirectly providing care to COVID-19 patients. Methods Prospective, observational study performed from July 28 to September 27, 2020, in Brazil, with women physicians from 47 specialities, the most frequent being cardiology (22.8%), with no age restriction. They voluntarily answered an online survey with questions on demographic and socioeconomic characteristics, quality of life (WHOQOL-brief), spirituality (WHOQOL-SRPB), and statements from the Oldenburg Burnout Inventory. Statistical analysis used the R software, beta regression, classification trees, and polychoric correlation matrix, with a 5% of significance level. Results Of the 769 respondents, 61.6% reported signs of burnout. About 64% reported wage loss of up to 50% during the pandemic. Some reported lack of energy for daily tasks, frequent negative feelings, dissatisfaction with capability for work, and caring for others not adding meaning to their lives. Negative feelings correlated negatively with satisfaction with sexual life and personal relations, and energy for daily tasks. The inability to remain optimistic in times of uncertainty correlated positively with feeling unsafe daily and not acknowledging that caring for others brings meaning to life. Conclusion This study showed a high frequency of burnout among Brazilian women physicians who answered the survey during the COVID-19 pandemic. Nevertheless, they presented with a relatively good quality of life and believed that spirituality comforted and reassured them in hard times.

The hypolipidemic and pleiotropic effects of rosuvastatin are not enhanced by its association with zinc and selenium supplementation in coronary artery disease patients: a double blind randomized controlled study.

OBJECTIVE: Statins treatment may modify the levels of zinc and selenium, minerals that can improve vascular function and reduce oxidative damage and inflammation in atherosclerotic patients. This study aimed to evaluate the effects of rosuvastatin, alone or associated with zinc and selenium supplementation, on lipid profile, antioxidant enzymes and mineral status in coronary artery disease patients. MATERIAL AND METHODS: A double-blind randomized clinical trial was performed in which patients (n = 76) were treated with 10 mg rosuvastatin over 4 months associated or not with zinc (30 mg/d) and selenium (150 µg/d) supplementation. The following parameters were analyzed before and after the intervention: anthropometric measurements, lipid profile, high sensitivity C-reactive protein (hs-CRP), electronegative low density lipoprotein (LDL(-)) concentrations, activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), zinc and selenium concentrations in blood plasma and erythocytes. Significance was determined using an α of 5% (two-tailed). RESULTS: We found that rosuvastatin therapy was efficient in reducing total cholesterol, LDL-cholesterol, non-HDL cholesterol, triglycerides, and hs-CRP independently of mineral supplementation. Neither treatment was associated with significant changes in LDL(-). Similarly, the antioxidant enzymes GPx and SOD activity were unchanged by treatments. Neither treatment was associated with significant differences in concentrations of zinc or selenium in blood plasma and erythocytes of studied groups. CONCLUSION: Rosuvastatin treatment did not affect zinc and selenium levels in coronary artery disease patients. The zinc and selenium supplementation at doses used in this study did not change lipid profile or SOD and GPx activity in patients receiving rosuvastatin. Further studies should be focused on testing alternative doses and supplements in different populations to contribute for a consensus on the ideal choice of antioxidants to be used as possible complementary therapies in atherosclerotic patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01547377.

The beneficial effects of rosuvastatin are independent of zinc supplementation in patients with atherosclerosis.

BACKGROUND: Statins have multiple antiatherosclerotic effects, but can reduce blood plasma concentrations of minerals, including zinc. As zinc possesses antiinflammatory and antioxidant effects, low zinc status can promote injuries or inadequate tissue repair in endothelial cells. Metallothionein (MT) expression might modulate responses induced by statins in patients with atherosclerosis. However, research regarding mineral status and the use of statins is scarce. This study evaluated the effects of zinc supplementation on zinc status and expression of the zinc-dependent MT1F and MT2A genes in patients with atherosclerosis treated with rosuvastatin. METHODS: A double-blind, randomized clinical trial was performed with 54 participants treated with 10mg rosuvastatin for 4 months with or without zinc supplementation (30mg/day). Diet, lipid profile, high-sensitivity reactive protein C (hs-CRP), plasma and erythrocyte zinc concentrations, erythrocyte superoxide dismutase (SOD) activity, and MT1F and MT2A genes expression were analyzed before and after intervention. RESULTS: Rosuvastatin therapy was effective in reducing low- and non-high-density lipoprotein, total cholesterol, triglycerides, and hs-CRP levels, independent of zinc supplementation. Additionally, zinc treatment had no effect on SOD enzyme activity (P=0.201), plasma (P>0.671) and erythrocyte (P>0.123) zinc concentrations, or the pattern of MT1F and MT2A genes expression (P=0.088 and P=0.229, respectively). CONCLUSIONS: The effectiveness of rosuvastatin treatment is independent of the effects of zinc supplementation. Moreover, rosuvastatin treatment did not have a significant impact on zinc status or MT1F and MT2A genes expression in patients with atherosclerosis.

Relationship between circulating VCAM-1, ICAM-1, E-selectin and MMP9 and the extent of coronary lesions

OBJECTIVES: Inflammatory molecules play a role in the development of atherosclerosis, which is the primary origin of cardiovascular disorders. However, to the best of our knowledge, no study has attempted to investigate the relationship between these circulating molecules and the prediction of cardiovascular risk. The present study aimed to investigate the relationships of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin and matrix metalloproteinase 9 serum concentrations with the extent of coronary lesions. METHODS: Seventy-four individuals who were undergoing coronary angiography for the first time for diagnostic purposes were enrolled in this study. The extent of the coronary lesion was assessed using the Friesinger Index, and subjects were classified into four groups: no lesions, minor lesions, intermediate lesions and major lesions. Serum biochemical parameters and serum concentrations of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin and matrix metalloproteinase 9 were analyzed. RESULTS: The vascular cell adhesion molecule-1 concentration was higher than 876 ng/mL in individuals with intermediate and major lesions (p<0.001 and p=0.020, respectively). Moreover, logistic regression analysis showed that these patients had an increased risk of having an intermediate lesion (p=0.007). Interestingly, all individuals with major lesions had vascular cell adhesion molecule-1 concentrations higher than 876 ng/mL. No association was found between the concentrations of the other proteins and the Friesinger Index. CONCLUSIONS: Serum vascular cell adhesion molecule-1 may be associated with the extent of coronary lesions. Moreover, it may represent an alternative to improve the cardiovascular risk classification in patients without acute coronary syndrome.

Prevalência de estenose da artéria subclávia em pacientes candidatos a cirurgia de revascularização do miocárdio: registro multicêntrico / Prevalence of stenosis of the left subclavia artery in CABG candidates: a multicenter registry

Introdução: Aproximadamente 90 por cento dos pacientes submetidos a cirurgia de revascularização do miocárdio (CRM) recebem enxerto de artéria torácica interna esquerda. A ocorrência de estenose da artéria subclávia esquerda pode resultar em falência do enxerto por limitação de fluxo coronário. A prevalência de estenose da artéia subclávia esquerda em pacientes com aterosclerose coronária grave, considerados candidatos a CRM, não é conhecida. Objetivo: Determinar a prevalência e a eficácia da avaliação clínica para diagnóstico a estenose da artéria subclávia esquerda em candidatos a CRM. Método: Em um registro multicêntrico, realizou-se angiografia seletiva da artéria subclávia esquerda em pacientes com indicação de CRM na ocasião da cinecoronariografia. Estenoses maiores ou iguais a 50 por cento antes da origem da artéria torácica interna foram considerdas significativas. Resultados: Dos 205 pacientes estudados, 16 (7,8 por cento) apresentavam estenose significativa da artéria subclávia esquerda. A medida da pressão arterial não-invasiva diferencial entre...

Background: Approximately 90% of the patients submitted to coronary artery bypass graft surgery (CABG) receive a left internal thoracic artery (LITA) graft. Stenosis of the left subclavian artery can result in graft failure due to restricted coronary flow. The prevalence of stenosis of the left subclavian artery in patients with severe coronary atherosclerosis, deemed candidates to CABG, is not known. Objective: To assess the prevalence of stenosis of left subclavian artery in CABG candidates, as well as the diagnostic effectiveness of clinical evaluation. Methods: In a multicenter registry, selective angiography of the left subclavian artery was carried out in patients considered candidates to CABG during coronary cineangiography. Stenoses ≥ 50% proximal to the origin of the LITA were considered significant. Results: A total of 205 patients were included. Significant stenosis of the left subclavian artery was observed in 16 (7.8%) patients. Noninvasive differential arterial blood pressure measurement ≥ 10 mmHg between both arms showed low sensitivity (37.5%) and low positive predictive value (13.3%) for stenosis identification. No clinical predictors of significant stenosis were identified by univariate analysis. Conclusion: Stenosis of the left subclavian artery is not uncommon in CABG candidates. Noninvasive blood pressure gradient between both arms has low diagnostic accuracy. Therefore, in patients candidates to CABG, selective angiography of the left subclavian artery should be considered, because of the risk of reduced flow and coronary-subclavian steal syndrome in patients with non-diagnosed stenosis of the subclavian artery who receive a LITA graft.