Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

ESTUDO DO BAGAÇO DE MANDIOCA (Manihot esculenta C.), NATIVO E TRATADO COM α AMILASE E AMILOGLUCOSIDASE, POR MEIO DE TÉCNICAS TERMOANALÍTICAS

A geração de resíduos é um problema diário para grande parte das agroindústrias em virtude da toxicidade ou grande volume gerado. Atualmente, políticas ambientais exigem o tratamento de resíduos antes do descarte na natureza. Além disso, este tratamento de resíduos é repassado aos custos de produção para o produto final. Propostas estão sendo apresentadas pelo setor ambiental com a finalidade de um uso racional para esses resíduos gerados. A indústria do amido, em especial o extraído da mandioca, produz quantidades significativas de rejeitos que podem ser empregados de forma racional, evitando seu descarte na natureza e gerando novos produtos. O bagaço da mandioca é esse tipo de resíduo, pois apresenta em sua composição alto teor de amido e fibras alimentares. Após o processamento, esse amido, por meio de ação de enzimas amilolíticas, pode ser convertido em xarope de maltose ou glicose, produtos de maior valor agregado, utilizados principalmente na indústria cervejeira. As análises via úmida para caracterizar a composição deste bagaço já foram realizadas, mas suas principais desvantagens estão associadas ao tempo requerido para a obtenção de resultados. Em função disso, o presente estudo visa analisar o bagaço de mandioca por várias frentes, sendo a análise térmica a principal entre as demais. As técnicas termoanalíticas empregadas foram a termogravimetria (TG), análise térmica diferencial (DTA), termogravimetria derivada (DTG) e a calorimetria exploratória diferencial (DSC). Assim como em trabalhos anteriores, a microscopia óptica foi utilizada provando-se de grande utilidade na identificação desse tipo de amostra. A difratometria de raios X pelo método do pó, classicamente utilizada no estudo de amidos em virtude de sua semi-cristalinidade, foi empregada neste tipo de resíduo. Como o processo hidrolítico quando empregado em fontes amiláceas produz quantidades significativas de açúcares redutores, a fase líquida resultante do processo foi analisada pela reação de redução com o ácido dinitrossalicílico (DNS). As temperaturas de degradação térmica obtidas a partir da análise termogravimétrica do bagaço de mandioca nativo e hidrolisado apresentaram redução, bem como alteração nas entalpias dos eventos de decomposição e combustão. A análise da calorimetria exploratória diferencial evidenciou uma temperatura de fusão do amido presente no bagaço de mandioca em 170C. Essa temperatura reduziu gradativamente à medida que as amostras foram hidrolisadas durante doze e vinte quatro horas, respectivamente 162.5 C e 152.3C.Waste generation represent a daily problem for most of the agriculture industry due to its toxicity and/or volume produced. Nowadays these residues demands treatment before its discard in the environment. Besides, the amounts spent with treatment are aggregated to manufacturing costs. Rational use of the residues seems to be the best way to handle with this problem. Cassava roots processing industry, produces significant amount of solid and liquid wastes from which valuable products could be extracted. Cassava bagasse is one of these residues containing high amounts of starch and dietary fibers. Before processing, the starch, through amylolitic enzyme digestion yields glucose and maltose syrups, products with wide uses in industry, for example, brewing industry. Classic laboratory analyses were already used in the characterization of cassava bagasse, but too much time were necessary to obtain results. Hence the present study aims for the analysis of cassava bagasse from multiple ways, being the thermal analysis the most important of all. The thermal techniques employed were thermogravimetry (TG), differential thermal analysis (DTA), derivate thermogravimetry (DTG) and differential scanning calorimetry (DSC). As in other past studies, optic microscopy proved its use in the identification of this kind of sample. X ray powder diffractometry is classically employed in the study of semi-cristalinity starch granule structure and was used to analyze the cassava bagasse. When a hydrolytic process is applied to starchy material, significant amount of reducing sugars are produced. Dinitrosalicylic acid (DNS) reducing reaction was performed in the hydrolyzed liquid fraction. The degradation temperatures obtained through thermogravimetric analysis of the native and hydrolyzed solid fractions of the cassava bagasse suffer reduction as well as changes in enthalpy and combustion values were noticed. DSC also showed fusion temperature of the starch in the cassava bagasse around 170 C. This value gradually reduced to 162.5 C and 152.3 C when the samples were hydrolyzed for twelve and twenty-four hours, respectively

Thermoanalytical and starch content evaluation of cassava bagasse as agro-industrial residue

Starch nutritional fractions as well as thermal properties and other analysis are essential for food and industrial application. Cassava bagasse is an important agro-industrial residue and its starch content was evaluated using two alternative methods. Thermal characterization and microscopy analyses helped to understand how hydrolysis digests starchy fraction of cassava bagasse. The melting point of cassava starch occurred at 169.2ºC. Regarding TG analyses, after moisture content, there were observed two main mass losses for all samples. Results suggest hydrolysis carried out using enzyme is less effective in order to convert total starch content in cassava bagasse. However, using sulfuric acid, fibers are affected by analyses conditions

Thermal analysis as a screening technique for the characterization of babassu flour and its solid fractions after acid and enzymatic hydrolysis

The babassu (Orbignya phalerata) is a native tree found in northern Brazil. Extracts of the babassu coconut have been widely used in industry. Babassu flour has about 60% starch, thus, besides nourishment it can be used as an alternative biofuel source. However, the properties of this starch lack of study and understanding. The main purpose of this study was to investigate the thermal behavior of raw babassu flour and its solid hydrolyzed fraction. The analyses were carried out using SHIMADZU DSC and TG thermic analyzers. The results demonstrated a reduction in thermal stability of the solid hydrolyzed fraction compared to raw matter. The kinetic parameters were investigated using non-isothermal methods and the parameters obtained for its decomposition process were an E(a) of 166.86 kJ mol(-1) and a frequency factor (beta) of 6.283 x 1014 min(-1); this was determined to be a first order reaction (n = 1). (C) 2011 Elsevier B.V. All rights reserved

Development and validation of the MMCD score to predict kidney replacement therapy in COVID-19 patients

Abstract Background Acute kidney injury (AKI) is frequently associated with COVID-19, and the need for kidney replacement therapy (KRT) is considered an indicator of disease severity. This study aimed to develop a prognostic score for predicting the need for KRT in hospitalised COVID-19 patients, and to assess the incidence of AKI and KRT requirement. Methods This study is part of a multicentre cohort, the Brazilian COVID-19 Registry. A total of 5212 adult COVID-19 patients were included between March/2020 and September/2020. Variable selection was performed using generalised additive models (GAM), and least absolute shrinkage and selection operator (LASSO) regression was used for score derivation. Accuracy was assessed using the area under the receiver operating characteristic curve (AUC-ROC). Results The median age of the model-derivation cohort was 59 (IQR 47–70) years, 54.5% were men, 34.3% required ICU admission, 20.9% evolved with AKI, 9.3% required KRT, and 15.1% died during hospitalisation. The temporal validation cohort had similar age, sex, ICU admission, AKI, required KRT distribution and in-hospital mortality. The geographic validation cohort had similar age and sex; however, this cohort had higher rates of ICU admission, AKI, need for KRT and in-hospital mortality. Four predictors of the need for KRT were identified using GAM: need for mechanical ventilation, male sex, higher creatinine at hospital presentation and diabetes. The MMCD score had excellent discrimination in derivation (AUROC 0.929, 95% CI 0.918–0.939) and validation (temporal AUROC 0.927, 95% CI 0.911–0.941; geographic AUROC 0.819, 95% CI 0.792–0.845) cohorts and good overall performance (Brier score: 0.057, 0.056 and 0.122, respectively). The score is implemented in a freely available online risk calculator ( https://www.mmcdscore.com/ ). Conclusions The use of the MMCD score to predict the need for KRT may assist healthcare workers in identifying hospitalised COVID-19 patients who may require more intensive monitoring, and can be useful for resource allocation

ABC-SPH risk score for in-hospital mortality in COVID-19 patients : development, external validation and comparison with other available scores

The majority of available scores to assess mortality risk of coronavirus disease 2019 (COVID-19) patients in the emergency department have high risk of bias. Therefore, this cohort aimed to develop and validate a score at hospital admission for predicting in-hospital mortality in COVID-19 patients and to compare this score with other existing ones. Consecutive patients (≥ 18 years) with confirmed COVID-19 admitted to the participating hospitals were included. Logistic regression analysis was performed to develop a prediction model for in-hospital mortality, based on the 3978 patients admitted between March-July, 2020. The model was validated in the 1054 patients admitted during August-September, as well as in an external cohort of 474 Spanish patients. Median (25-75th percentile) age of the model-derivation cohort was 60 (48-72) years, and in-hospital mortality was 20.3%. The validation cohorts had similar age distribution and in-hospital mortality. Seven significant variables were included in the risk score: age, blood urea nitrogen, number of comorbidities, C-reactive protein, SpO/FiO ratio, platelet count, and heart rate. The model had high discriminatory value (AUROC 0.844, 95% CI 0.829-0.859), which was confirmed in the Brazilian (0.859 [95% CI 0.833-0.885]) and Spanish (0.894 [95% CI 0.870-0.919]) validation cohorts, and displayed better discrimination ability than other existing scores. It is implemented in a freely available online risk calculator (https://abc2sph.com/). An easy-to-use rapid scoring system based on characteristics of COVID-19 patients commonly available at hospital presentation was designed and validated for early stratification of in-hospital mortality risk of patients with COVID-19

ABC₂-SPH risk score for in-hospital mortality in COVID-19 patients

Objectives: The majority of available scores to assess mortality risk of coronavirus disease 2019 (COVID-19) patients in the emergency department have high risk of bias. Therefore, this cohort aimed to develop and validate a score at hospital admission for predicting in-hospital mortality in COVID-19 patients and to compare this score with other existing ones. Methods: Consecutive patients (≥ 18 years) with confirmed COVID-19 admitted to the participating hospitals were included. Logistic regression analysis was performed to develop a prediction model for in-hospital mortality, based on the 3978 patients admitted between March–July, 2020. The model was validated in the 1054 patients admitted during August–September, as well as in an external cohort of 474 Spanish patients. Results: Median (25–75th percentile) age of the model-derivation cohort was 60 (48–72) years, and in-hospital mortality was 20.3%. The validation cohorts had similar age distribution and in-hospital mortality. Seven significant variables were included in the risk score: age, blood urea nitrogen, number of comorbidities, C-reactive protein, SpO2/FiO2 ratio, platelet count, and heart rate. The model had high discriminatory value (AUROC 0.844, 95% CI 0.829–0.859), which was confirmed in the Brazilian (0.859 [95% CI 0.833–0.885]) and Spanish (0.894 [95% CI 0.870–0.919]) validation cohorts, and displayed better discrimination ability than other existing scores. It is implemented in a freely available online risk calculator (https://abc2sph.com/). Conclusions: An easy-to-use rapid scoring system based on characteristics of COVID-19 patients commonly available at hospital presentation was designed and validated for early stratification of in-hospital mortality risk of patients with COVID-19.</p

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)