Prevalence, incidence, risk factors and residual risk associated with viral infections among eligible Brazilian blood donors.

Knowledge regarding the profile of eligible blood donors presenting positive results in laboratory screening is essential for reducing transfusion-transmitted human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV). Our study aimed to evaluate the prevalence, incidence, predictor variables and residual risk (RR) of HIV/HBV/HCV in blood bags donated in Minas Gerais, Brazil. This study analysed data retrieved from the records of a large blood bank relating to donations collected at multiple centres within the period 2012-2018, during which 1 991 120 blood bags were screened using immunoassays and nucleic acid tests (NATs). Multilevel modelling was used to investigate the association between sex, civil status and age group with HIV/HBV/HCV. RR was estimated from the incidence values (restricted to negative and positive tests within the study period) and window periods for infections. The prevalence in first time donors, incidence and RR of HCV (223.73 cases per 100 000; 54.84 per 100 000 persons-year and 1.6527 per 100 000, respectively) were higher than those of HIV (172.65 cases per 100 000; 28.25 per 100 000 persons-year and 0.8514 per 100 000) and HBV (168.17 cases per 100 000; 18.54 per 100 000 persons-year and 0.5588 per 100 000). The odds of acquiring infection were greater in male, single and older donors. Sixteen donors were identified as seronegative and NATs+ during the 7-year span of the study. Our study has clarified some spatiotemporal trends regarding HIV/HBV/HCV infections in donated blood in Brazil. The results will contribute to the formulation of directives addressed to high-risk donors.

Clinical characteristics and outcomes of COVID-19 patients with preexisting dementia: a large multicenter propensity-matched Brazilian cohort study.

BACKGROUND: Although dementia has emerged as an important risk factor for severe SARS-CoV-2 infection, results on COVID-19-related complications and mortality are not consistent. We examined the clinical presentations and outcomes of COVID-19 in a multicentre cohort of in-hospital patients, comparing those with and without dementia. METHODS: This retrospective observational study comprises COVID-19 laboratory-confirmed patients aged ≥ 60 years admitted to 38 hospitals from 19 cities in Brazil. Data were obtained from electronic hospital records. A propensity score analysis was used to match patients with and without dementia (up to 3:1) according to age, sex, comorbidities, year, and hospital of admission. Our primary outcome was in-hospital mortality. We also assessed admission to the intensive care unit (ICU), invasive mechanical ventilation (IMV), kidney replacement therapy (KRT), sepsis, nosocomial infection, and thromboembolic events. RESULTS: Among 1,556 patients included in the study, 405 (4.5%) had a diagnosis of dementia and 1,151 were matched controls. When compared to matched controls, patients with dementia had a lower frequency of dyspnoea, cough, myalgia, headache, ageusia, and anosmia; and higher frequency of fever and delirium. They also had a lower frequency of ICU admission (32.7% vs. 47.1%, p < 0.001) and shorter ICU length of stay (7 vs. 9 days, p < 0.026), and a lower frequency of sepsis (17% vs. 24%, p = 0.005), KRT (6.4% vs. 13%, p < 0.001), and IVM (4.6% vs. 9.8%, p = 0.002). There were no differences in hospital mortality between groups. CONCLUSION: Clinical manifestations of COVID-19 differ between older inpatients with and without dementia. We observed that dementia alone could not explain the higher short-term mortality following severe COVID-19. Therefore, clinicians should consider other risk factors such as acute morbidity severity and baseline frailty when evaluating the prognosis of older adults with dementia hospitalised with COVID-19.

Plasma immune mediators as laboratorial biomarkers for Sickle Cell Disease patients according to the hydroxyurea therapy and disease severity.

In the present work, the impact of Sickle Cell Disease (SCD) degrees of severity, as well hydroxyurea treatment on the systemic immunological signatures of patients was evaluated. Based on a high-throughput chemokine, cytokine and growth factor multiplex analysis, it was possible to obtain the systemic immunological profile of patients with SCD (n = 40), treated or not with hydroxyurea, as compared to healthy controls (n = 40). Overall, SCD patients with severe disease displayed increased levels of almost all biomarkers analyzed. Our data demonstrated that CXCL8, CCL3 and CXCL10 were pointed out as universal biomarkers of SCD. The results also indicated that HU-untreated patients with indication of HU-therapy display a more prominent increase on plasma immune mediators in a similar way as those with severe SCD disease. Together, these findings provided a comprehensive landscape of evidence that may have implications for further therapeutic strategies and SCD clinical management.

Effect of Different Classes of Antihypertensive Drugs on Arterial Stiffness.

PURPOSE OF REVIEW: To describe the physiological aspects of blood pressure and arterial stiffness, as well as explain how these processes are related. To review the available evidence on the effect of treatment with different classes of antihypertensive drugs on improving arterial stiffness. RECENT FINDINGS: Specific classes of antihypertensive drugs may have effects directly on improving arterial stiffness independent of lowering blood pressure. The maintenance of normal blood pressure levels is essential for the homeostasis of the whole organism; the increase in blood pressure is directly related to the increased risk of cardiovascular diseases. Hypertension is characterized by structural and functional changes in blood vessels and is associated with a more accelerated progression of arterial stiffness. Randomized clinical trials have shown that some specific classes of antihypertensive drugs can improve arterial stiffness independently of their effect on lowering brachial blood pressure. These studies show that calcium channel blockers (CCBs), angiotensin II receptor blockers (ARBs), and angiotensin-converting enzyme (ACE) inhibitors have been shown to have a better effect on arterial stiffness compared to diuretics and beta-blockers in individuals with arterial hypertension and other cardiovascular risk factors. More real-world studies are needed to assess whether this effect on arterial stiffness can improve the prognosis of patients with hypertension.

Use of Antihypertensive Drugs and Arterial Stiffness in the Longitudinal Study of Adult Health (ELSA-Brasil).

OBJECTIVE: Evaluate the longitudinal association between BP control and the use of antihypertensive classes with arterial stiffness (AS) in Brazilian adults. METHODS: This study included 1830 participants with arterial hypertension (1092 participants with controlled BP and 738 participants with uncontrolled BP) from the Longitudinal Study of Adult Health (ELSA-Brasil). AS was assessed by pulse wave velocity (PWV) and pulse pressure (PP) at baseline and repeated after approximately 9 years. Associations between AS and BP control and the use of antihypertensives, diuretics, angiotensin-converting enzyme inhibitors (ACEI), AT1 receptor blockers (ARB), calcium channel blockers (CCB), and beta blockers (in the population with controlled BP), at baseline were investigated using linear mixed-effects models. RESULTS: Uncontrolled BP was associated with worse PWV and PP trajectory, respectively (ß = 0.026 [0.008 to 0.036] / ß = 0.273 [0.216 to 0.330]). Among the participants with controlled BP, using CCB (ß = 0.031 [0.011 to 0.051]) was associated with a worse PWV trajectory, compared to not using this class and this combination, respectively. CONCLUSION: BP control, regardless of the class of antihypertensive used is associated with a better AS trajectory, as assessed by PWV and PP. Among participants with controlled BP, the use of BCC, compared to not using this class, seems to be worse for the trajectory of PWV in individuals with arterial hypertension without cardiovascular disease. Further studies are needed to assess whether this effect results in a better prognosis for patients with arterial hypertension.

Temporal validation of the MMCD score to predict kidney replacement therapy and in-hospital mortality in COVID-19 patients.

BACKGROUND: Acute kidney injury has been described as a common complication in patients hospitalized with COVID-19, which may lead to the need for kidney replacement therapy (KRT) in its most severe forms. Our group developed and validated the MMCD score in Brazilian COVID-19 patients to predict KRT, which showed excellent performance using data from 2020. This study aimed to validate the MMCD score in a large cohort of patients hospitalized with COVID-19 in a different pandemic phase and assess its performance to predict in-hospital mortality. METHODS: This study is part of the "Brazilian COVID-19 Registry", a retrospective observational cohort of consecutive patients hospitalized for laboratory-confirmed COVID-19 in 25 Brazilian hospitals between March 2021 and August 2022. The primary outcome was KRT during hospitalization and the secondary was in-hospital mortality. We also searched literature for other prediction models for KRT, to assess the results in our database. Performance was assessed using area under the receiving operator characteristic curve (AUROC) and the Brier score. RESULTS: A total of 9422 patients were included, 53.8% were men, with a median age of 59 (IQR 48-70) years old. The incidence of KRT was 8.8% and in-hospital mortality was 18.1%. The MMCD score had excellent discrimination and overall performance to predict KRT (AUROC: 0.916 [95% CI 0.909-0.924]; Brier score = 0.057). Despite the excellent discrimination and overall performance (AUROC: 0.922 [95% CI 0.914-0.929]; Brier score = 0.100), the calibration was not satisfactory concerning in-hospital mortality. A random forest model was applied in the database, with inferior performance to predict KRT requirement (AUROC: 0.71 [95% CI 0.69-0.73]). CONCLUSION: The MMCD score is not appropriate for in-hospital mortality but demonstrates an excellent predictive ability to predict KRT in COVID-19 patients. The instrument is low cost, objective, fast and accurate, and can contribute to supporting clinical decisions in the efficient allocation of assistance resources in patients with COVID-19.

Endothelial dysfunction biomarkers in sickle cell disease: is there a role for ADMA and PAI-1?

Within the spectrum of sickle cell disease (SCD) are sickle cell anemia (SCA), presence of hemoglobin SS (HbSS), hemoglobin SC disease (HbSC), and sickle cell ß-thalassemia (Sß-thal). Asymmetric dimethylarginine (ADMA) competitively inhibits the binding of arginine to NOS, reducing NO production. In patients with HbSS, increased levels of ADMA have been reported, as well as changes in many hemostatic biomarkers, including the plasminogen activator inhibitor type 1 (PAI-1). We hypothesized that high levels of ADMA and PAI-1 may be associated with more severe SCD. Thus, ADMA and PAI-1 levels were determined in 78 individuals including 38 adult patients with SCD and 40 control subjects. Higher levels of ADMA were shown in HbSS and Sß-thal patients compared to controls. Concerning PAI-1, all patients showed high levels of PAI-1 compared to controls. As a role of NO in the pathogenesis of SCD has already been established, we concluded that high levels of ADMA should compromise, at least in part, NO synthesis, resulting in endothelial dysfunction. Elevated plasma levels of PAI-1 in all patients may indicate not only endothelial dysfunction but also a hypofibrinolytic state favoring thrombotic complications. Finally, high levels of ADMA and PAI-1 may be associated with more severe SCD.

ADAMTS-13-VWF axis in sickle cell disease patients.

Sickle cell disease (SCD) comprises a group of genetic disorders characterized by the presence of the hemoglobin (Hb) S in homozygosis or in heterozygosis with some other Hb variant or in interaction with thalassemia. SCD is characterized by a very complex pathophysiology, which determines a wide variability of clinical manifestations, including a chronic state of hypercoagulability responsible for the increased risk of thromboembolic events. ADAMTS13 and von Willebrand factor (VWF) play an important role in arterial and venous thrombosis. Thus, the aim of this study was to understand how the ADAMTS13-VWF axis behaves in sickle cell disease, as well as whether there is an association of these markers with the use of hydroxyurea (HU). This is a cross-sectional study conducted with 40 patients diagnosed with SCD and 40 healthy individuals. The analysis of the ADAMTS13-VWF axis was comparatively performed between groups of patients and controls and, afterwards, between patients with SCD who were users and non-users of HU. ADAMTS13 activity, ADAMTS13 activity/VWF:Ag, and ADAMTS13:Ag/VWF:Ag ratios were significantly lower and VWF:Ag levels significantly higher in SCD patients when compared to the controls. There was no statistically significant difference in ADAMTS13:Ag and VWF collagen binding (VWF:CB) levels between the groups evaluated. Among the categories of HU use, there was no statistically significant difference in any of the evaluated markers. As a conclusion, we could observe that the ADAMTS13-VWF axis is altered in SCD when compared to healthy individuals and that there is no association between these markers and the use of HU.

Thrombin Generation and other hemostatic parameters in patients with atrial fibrillation in use of warfarin or rivaroxaban.

Patients with atrial fibrillation (AF) present hyperactivation of both platelets and coagulation leading to a hypercoagulable state which contributes to an increased risk of thromboembolism. Therefore, one of the main strategies for treatment of AF is prevention of these events through the use of oral anticoagulants (OAC). The aim of this study was to evaluate hemostasis as a whole in patients with non-valvular AF undergoing warfarin or rivaroxaban by thrombin generation test (TGT), in addition to monocyte-platelet aggregates (MPA), glycoprotein IIb/IIIa (GPIIb/IIIa), and platelet (PMP) and endothelium (EMP) microparticles, compared to age and sex matched controls. PT/INR for OAC use was also determined. In patients taking OAC, compared to control group, a decrease in TGT (p = 0.000 for all parameters) were observed. Patients taking warfarin showed to be more hypocoagulable, presenting lower levels of ETP (p = 0.000) and peak (p = 0.002) than patients using rivaroxaban. Patients on warfarin use with INR > 3 had also lower levels of ETP (p = 0.01) and peak (p = 0.006). A decrease in ETP (p = 0.03) and peak (p = 0.02) values was also observed in patients using rivaroxaban with PT > 21.4 s. Patients using warfarin (p = 0.000) and rivaroxaban (p = 0.000) presented lower levels of MPA in relation to control group. It was also observed in patients using warfarin, lower GPIIb/IIIa levels in relation to control group (p = 0.011). Patients taking rivaroxaban (p = 0.003) and warfarin (p = 0.001) had higher PMP levels compared to control group. There was no difference in levels of EMP between the groups (p = 0.0536). The present study reinforces the usefulness of OAC in AF, which decisively contribute to a better management of the disease preventing possible complications.

Association between dyslipidemia and CCL2 in patients undergoing hemodialysis.

INTRODUCTION: Hemodialysis (HD) is associated with high risk for cardiovascular diseases including acute myocardial infarction, stroke and congestive heart failure. C-C Motif Chemokine Ligand 2 (CCL2), also known monocyte chemotactic protein-1 (MCP-1) can be produced by a variety of cells, reaching increased levels in dyslipidemic chronic kidney disease (CKD) patients undergoing HD treatment. The main of this study was to evaluate the association between of CCL2 plasma levels and dyslipidemia in CKD patients undergoing HD. METHODS: A cross-sectional study enrolled 160 Brazilian HD patients. CCL2 plasma levels were measured by capture ELISA. The association between CCL2 levels and dyslipidemia was investigated using linear regression, adjusted for classic and non-classical CVD risk factors. RESULTS: A significant association was observed between CCL2 levels and dyslipidemia (P = 0.029), even after adjustment for possible confounding variables, such as age, gender, body mass index, diabetes mellitus, HD time, urea pre-hemodialysis and interdialytic weight gain (P = 0.045). CONCLUSION: Our findings show that CCL2 levels are associated with dyslipidemia, which suggests a role of this cytokine in the pathogenesis of cardiovascular disease in HD patients. A better understanding of this pathogenesis could contribute to the discovery of new therapeutic targets that would reduce cardiovascular complications in these patients.

Effect of Different Classes of Antihypertensive Drugs on Endothelial Function and Inflammation.

Hypertension is characterized by structural and functional changes in blood vessels that travel with increased arterial stiffness, vascular inflammation, and endothelial dysfunction. Some antihypertensive drugs have been shown to improve endothelial function and reduce levels of inflammatory markers regardless of the effect of blood pressure lowering. Third-generation ß-blockers, such as nebivolol and carvedilol, because they have additional properties, have been shown to improve endothelial function in patients with hypertension. Calcium channel antagonists, because they have antioxidant effects, may improve endothelial function and vascular inflammation.The Angiotensin Receptor Blocker (ARBs) are able to improve endothelial dysfunction and vascular inflammation in patients with hypertension and other cardiovascular diseases. Angiotensin converting enzyme (ACE) inhibitors have shown beneficial effects on endothelial function in patients with hypertension and other cardiovascular diseases, however there are few studies evaluating the effect of treatment with this class on the reduction of C-reactive protein (CRP) levels. Further studies are needed to assess whether treatment of endothelial dysfunction and vascular inflammation may improve the prognosis of patients with essential hypertension.

Study of association between interleukin-17 and interferon-gamma and recombinant human erythropoietin dose in patients undergoing peritoneal dialysis.

BACKGROUND: A common complication in patients undergoing peritoneal dialysis (PD) is a chronic inflammatory state and anemia that can be treating by recombinant human erythropoietin (rHuEPO). Higher required dose of rHuEPO could be expected in patients with higher cytokine levels. Additionally, it is known that peritoneal inflammation can be correlated with systemic inflammation and this could contribute to the compromised rHuEPO required dose in anemic patients with end stage renal disease (ESRD). Thus, the current study aimed to evaluate the association between levels of systemic and local interferon (IFN)-γ, interleukin (IL)-17 and other cytokines and the dose of rHuEPO used by patients undergoing PD for the correction of anemia. METHODS: Thirty-one patients under PD using rHuEPO were evaluated in this cross-sectional study. Plasma and dialysate levels of IL-2, IL-4, IL-6, IL-10, IL-17, tumour necrosis factor (TNF)-α and IFN-γ were determined using the Cytometric Bead Array TM kit (CBA; BD Bioscences, San Jose, CA). The relation between the levels of each cytokine levels and the tertiles of rHuEPO were plotted on box-plot graphics and then the medians of interleukins levels were compared by median comparison test. The significance level adopted was 5% and the analysis was performed by the softwares STATA (version 12.0) and GraphPad Prism 3.0. RESULTS: The median of IL-17 and IFN-γ plasma levels were significant higher in the group with higher rHuEPO dosage. However, this association was not observed in the dialysate levels, as well as was not observed a relationship between the other plasma and dialysate cytokines evaluated in this study and the dose of rHuEPO. CONCLUSIONS: Our study found increased IL-17 and IFN-γ plasma, but no dialysate levels, in patients receiving higher doses of rHuEPO, suggesting may exist a relationship between systemic inflammation of ESRD, and the necessary levels of rHuEPO for the correction of anemia in these patients.

ABO blood group polymorphisms and risk for ischemic stroke and peripheral arterial disease.

Recent studies have demonstrated association between ABO blood system and thrombosis, indicating that individuals belonging to non-O blood groups (A, B or AB) present an increased risk of venous thrombosis, heart disease, and ischemic stroke (IS) as compared to O blood group carriers. In this study, we investigated the frequency of ABO blood group polymorphisms and its association with IS and peripheral arterial disease. Significant differences were observed for O1 (OR 0.57, 95% CI 0.35-0.95, p < 0.05) and O2 (OR 3.47, 95% CI 1.15-10.28, p < 0.05) alleles among IS patients while significant differences were observed for B phenotype (26.3 vs 9.5%, OR 3.42, 95% CI 1.32-8.76, p = 0.01, patients vs controls, respectively) and alleles A1 (OR 0.31, 95% CI 0.11-0.84, p < 0.05), O2 (OR 4.61, 95% CI 1.59-13.23, p < 0.01) and B (OR 3.42, 95% CI 1.62-7.13, p < 0.001) alleles for PAD patients. O1 allele was an independent variable (OR 0.27, 95% CI 0.12-0.57, p < 0.001) for IS patients. These data suggest the relationship of non-O blood groups in pathogenesis of thrombosis events and a possible protective effect of O blood group.

AB2CO risk score for in-hospital mortality of COVID-19 patients admitted to intensive care units.

PURPOSE: To develop a mortality risk score for COVID-19 patients admitted to intensive care units (ICU), and to compare it with other existing scores. MATERIALS AND METHODS: This retrospective observational study included consecutive adult patients with laboratory-confirmed COVID-19 admitted to ICUs of 18 hospitals from nine Brazilian cities, from September 2021 to July 2022. Potential predictors were selected based on the literature review. Generalized Additive Models were used to examine outcomes and predictors. LASSO regression was used to derive the mortality score. RESULTS: From 558 patients, median age was 69 years (IQR 58-78), 56.3 % were men, 19.7 % required mechanical ventilation (MV), and 44.8 % died. The final model comprised six variables: age, pO2/FiO2, respiratory function (respiratory rate or if in MV), chronic obstructive pulmonary disease, and obesity. The AB2CO had an AUROC of 0.781 (95 % CI 0.744 to 0.819), good overall performance (Brier score = 0.191) and an excellent calibration (slope = 1.063, intercept = 0.015, p-value = 0.834). The model was compared with other scores and displayed better discrimination ability than the majority of them. CONCLUSIONS: The AB2CO score is a fast and easy tool to be used upon ICU admission.

Hematological parameters: is there a difference between those released by the hematological analyzer and to the customer?

OBJECTIVE: This study aimed to compare the hematological parameters released by hematological analyzers with those released in customer reports. METHODS: We conducted a descriptive study in the laboratories of a medium-sized municipality in the state of Minas Gerais registered in the National Register of Health Establishments. Interviews were conducted using a questionnaire to obtain information regarding the parameters released by the analyzers and those available in the customer's report. RESULTS: Sixteen laboratories were evaluated, and none of them released all the parameters obtained from the hematological analyzers to customers. The red blood cell distribution width was released in 88% of the laboratories, atypical lymphocytes in 70%, mean platelet volume in 50%, platelet distribution width and platelet count in 20%. No laboratory released information on reticulocytes, fraction of immature reticulocytes and immature granulocytes, nucleated erythrocyte count, immature platelet fraction and reticulocyte hemoglobin, and large platelet rate. CONCLUSION: All evaluated clinical analysis laboratories had at least one parameter that was not released in the customer's report despite being released by the hematological analyzers. The lack of knowledge on the part of professionals about the clinical importance of each parameter of the complete blood count results in a loss in patient assessment, and it is important to include these parameters in the complete blood count report.

Assessment of the ABC2-SPH risk score to predict invasive mechanical ventilation in COVID-19 patients and comparison to other scores.

Background: Predicting the need for invasive mechanical ventilation (IMV) is important for the allocation of human and technological resources, improvement of surveillance, and use of effective therapeutic measures. This study aimed (i) to assess whether the ABC2-SPH score is able to predict the receipt of IMV in COVID-19 patients; (ii) to compare its performance with other existing scores; (iii) to perform score recalibration, and to assess whether recalibration improved prediction. Methods: Retrospective observational cohort, which included adult laboratory-confirmed COVID-19 patients admitted in 32 hospitals, from 14 Brazilian cities. This study was conducted in two stages: (i) for the assessment of the ABC2-SPH score and comparison with other available scores, patients hospitalized from July 31, 2020, to March 31, 2022, were included; (ii) for ABC2-SPH score recalibration and also comparison with other existing scores, patients admitted from January 1, 2021, to March 31, 2022, were enrolled. For both steps, the area under the receiving operator characteristic score (AUROC) was calculated for all scores, while a calibration plot was assessed only for the ABC2-SPH score. Comparisons between ABC2-SPH and the other scores followed the Delong Test recommendations. Logistic recalibration methods were used to improve results and adapt to the studied sample. Results: Overall, 9,350 patients were included in the study, the median age was 58.5 (IQR 47.0-69.0) years old, and 45.4% were women. Of those, 33.5% were admitted to the ICU, 25.2% received IMV, and 17.8% died. The ABC2-SPH score showed a significantly greater discriminatory capacity, than the CURB-65, STSS, and SUM scores, with potentialized results when we consider only patients younger than 80 years old (AUROC 0.714 [95% CI 0.698-0.731]). Thus, after the ABC2-SPH score recalibration, we observed improvements in calibration (slope = 1.135, intercept = 0.242) and overall performance (Brier score = 0.127). Conclusion: The ABC2-SPHr risk score demonstrated a good performance to predict the need for mechanical ventilation in COVID-19 hospitalized patients under 80 years of age.

Real-Life Data on Hydroxychloroquine or Chloroquine with or Without Azithromycin in COVID-19 Patients: A Retrospective Analysis in Brazil. / Dados de Vida Real sobre o Uso da Hidroxicloroquina ou da Cloroquina Combinadas ou Não à Azitromicina em Pacientes com Covid-19: Uma Análise Retrospectiva no Brasil.

BACKGROUND: Despite no evidence showing benefits of hydroxychloroquine and chloroquine with or without azithromycin for COVID-19 treatment, these medications have been largely prescribed in Brazil. OBJECTIVES: To assess outcomes, including in-hospital mortality, electrocardiographic abnormalities, hospital length-of-stay, admission to the intensive care unit, and need for dialysis and mechanical ventilation, in hospitalized COVID-19 patients who received chloroquine or hydroxychloroquine, and to compare outcomes between those patients and their matched controls. METHODS: A retrospective multicenter cohort study that included consecutive laboratory-confirmed COVID-19 patients from 37 Brazilian hospitals from March to September 2020. Propensity score was used to select matching controls by age, sex, cardiovascular comorbidities, and in-hospital use of corticosteroid. A p-value <0.05 was considered statistically significant. RESULTS: From 7,850 COVID-19 patients, 673 (8.6%) received hydroxychloroquine and 67 (0.9%) chloroquine. The median age in the study group was 60 years (46 - 71) and 59.1% were women. During hospitalization, 3.2% of patients presented side effects and 2.2% required therapy discontinuation. Electrocardiographic abnormalities were more prevalent in the chloroquine/hydroxychloroquine group (13.2% vs. 8.2%, p=0.01), and the long corrected QT interval was the main difference (3.6% vs. 0.4%, p<0.001). The median hospital length of stay was longer in the HCQ/CQ + AZT group than in controls (9.0 [5.0, 18.0] vs. 8.0 [4.0, 14.0] days). There was no statistical differences between groups in intensive care unit admission (35.1% vs. 32.0%; p=0.282), invasive mechanical ventilation support (27.0% vs. 22.3%; p=0.074) or mortality (18.9% vs. 18.0%; p=0.682). CONCLUSION: COVID-19 patients treated with chloroquine or hydroxychloroquine had a longer hospital length of stay, when compared to matched controls. Intensive care unit admission, invasive mechanical ventilation, dialysis and in-hospital mortality were similar.

FUNDAMENTO: Apesar da ausência de evidência mostrando benefícios da hidroxicloroquina e da cloroquina combinadas ou não à azitromicina no tratamento da covid-19, esses medicamentos têm sido amplamente prescritos no Brasil. OBJETIVOS: Avaliar desfechos, incluindo moralidade hospitalar, alterações eletrocardiográficas, tempo de internação, admissão na unidade de terapia intensiva, e necessidade de diálise e de ventilação mecânica em pacientes hospitalizados com covid-19 que receberam cloroquina ou hidroxicloroquina, e comparar os desfechos entre aqueles pacientes e seus controles pareados. MÉTODOS: Estudo multicêntrico retrospectivo do tipo coorte que incluiu pacientes com diagnóstico laboratorial de covid-19 de 37 hospitais no Brasil de março a setembro de 2020. Escore de propensão foi usado para selecionar controles pareados quanto a idade, sexo, comorbidades cardiovasculares, e uso de corticosteroides durante a internação. Um valor de p<0,05 foi considerado estatisticamente significativo. RESULTADOS: Dos 7850 pacientes com covid-19, 673 (8,6%) receberam hidroxicloroquina e 67 (0,9%) cloroquina. A idade mediana no grupo de estudo foi 60 (46-71) anos e 59,1% eram mulheres. Durante a internação, 3,2% dos pacientes apresentaram efeitos adversos e 2,2% necessitaram de interromper o tratamento. Alterações eletrocardiográficas foram mais prevalentes no grupo hidroxicloroquina/cloroquina (13,2% vs. 8,2%, p=0,01), e o prolongamento do intervalo QT corrigido foi a principal diferença (3,6% vs. 0,4%, p<0,001). O tempo mediano de internação hospitalar foi maior no grupo usando CQ/HCQ em relação aos controles (9,0 [5,0-18,0] vs. 8,0 [4,0-14,0] dias). Não houve diferenças estatisticamente significativas entre os grupos quanto a admissão na unidade de terapia intensiva (35,1% vs. 32,0%; p=0,282), ventilação mecânica invasiva (27,0% vs. 22,3%; p=0,074) ou mortalidade (18,9% vs. 18,0%; p=0,682). CONCLUSÃO: Pacientes com covid-19 tratados com cloroquina ou hidroxicloroquina apresentaram maior tempo de internação hospitalar, em comparação aos controles. Não houve diferença em relação a admissão em unidade de terapia intensiva, necessidade de ventilação mecânica e mortalidade hospitalar.

Thrombin generation assay as a biomarker of cardiovascular outcomes and mortality: A narrative review.

Cardiovascular diseases (CVDs) are currently the leading cause of death worldwide. Therefore, there is interest in the search for cardiovascular risk markers that contribute to the early diagnosis, monitoring and prevention of cardiovascular events. Considering that CVDs present in their pathophysiology a strong interaction between inflammation and hemostasis, thrombin, a key enzyme in the clotting process can be thought as a possible biomarker of cardiovascular risk. The thrombin generation assay (TGA) by the Calibrated Automated Thrombogram (CAT) method has been used in numerous prospective studies. It is a relatively recent laboratory tool capable of globally evaluating the functioning of the hemostatic system through the determination of thrombin generation for investigating the contribution of procoagulants and natural anticoagulants, in addition to the effect of different drugs and a range of factors that interfere in this system. The analysis of thrombin generation can be a promising tool for estimating the risk of thrombotic diseases, although the association of TGA with arterial thrombosis has only recently attracted interest and remains to be better understood. The association between thrombin generation and cardiovascular events, especially acute myocardial infarction (AMI) and stroke, all-cause and cardiovascular mortality is still poorly investigated and the results are often inconsistent. Assessing the relationship between TGA and CVDs may not only contribute to increasing knowledge of the pathophysiological process that leads to coronary and cerebrovascular diseases, but may also suggest a new approach to prevention. In this article we review and summarize the results of the main studies that evaluated whether TGA parameters were associated with cardiovascular events, cardiovascular mortality and all-cause mortality. Possible contributing factors to the observed inconsistencies were also speculated.

Quality of clinical studies present in the package inserts of coagulation factors used in the treatment of hemophilia.

OBJECTIVE: To identify and analyze the quality of scientific evidence from clinical efficacy studies present in the package inserts of coagulation factors, used in the treatment of hemophilia A and B. METHODS: Documentary study developed in two stages. The first stage consisted of identifying the medicine packages inserts electronically registered in the Brazilian Health Regulatory Agency, and analyzing the availability of the bibliographic references cited therein. This analysis was conducted in the PubMed, SciELO, Google Scholar, and Web of Science databases. The second step was the analysis of the methodological quality of the efficacy studies. Two trained researchers used the Cochrane Collaboration Risk of Bias version 5.1.0 tools for methodological quality analysis, and Review Manager 5.4 software to generate the risk of bias graph. RESULTS: Of the 17 medicines listed, 7 had referenced package inserts. Of these, 10 studies were eligible for analysis of methodological quality. More than half of the analyzed studies did not control for selection, performance, and detection bias. A total of 100% controlled attrition and reporting biases, and 50% had a high risk of conflict of interest. CONCLUSION: The biases present are significant and may have influenced the overestimation of the effects of the outcomes of each of the studies.

Renin angiotensin system molecules and chemokine (C-C motif) ligand 2 (CCL2) in chronic kidney disease patients.

INTRODUCTION: Studies have shown that the renin angiotensin aldosterone system (RAAS) and inflammation are related to kidney injury progression. The aim of this study was to evaluate RAAS molecules and chemokine (C-C motif) ligand 2 (CCL2) in 82 patients with chronic kidney disease (CKD). METHODS: Patients were divided into two groups: patients diagnosed with CKD and patients without a CKD diagnosis. Glomerular filtration rate (GFR) and albumin/creatinine ratio (ACR) were determined, as well as plasma levels of angiotensin-(1-7) [Ang-(1-7)], angiotensin-converting enzyme (ACE)1, ACE2, and plasma and urinary levels of CCL2. RESULTS: CCL2 plasma levels were significantly higher in patients with CKD compared to the control group. Patients with lower GFR had higher plasma levels of ACE2 and CCL2 and lower ratio ACE1/ACE2. Patients with higher ACR values had higher ACE1 plasma levels. CONCLUSION: Patients with CKD showed greater activity of both RAAS axes, the classic and alternative, and higher plasma levels of CCL2. Therefore, plasma levels of RAAS molecules and CCL2 seem to be promising prognostic markers and even therapeutic targets for CKD.