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AIM: To determine the correlation between the results of the 6-minute walk test (6MWT) and peak oxygen consumption (VO2peak) for populations of patients with chronic heart failure with pronounced clinical and demographic differences; to study a possibility of indirect measurement of VO2peak based on the results of 6MWT using the formulas available from the literature. MATERIAL AND METHODS: Two databases were analyzed: 50 patients included in the AEROFIT study (group A), and 31 patients from the Almazov National Medical Research Center (group B). The inclusion criteria were the availability of data from the cardiopulmonary stress test and the 6MWT. The possibility of predicting VO2peak was calculated based on the results of 6MWT using the formulas reported in the literature (L. P. Cahalin et al., 1996; R. M. Ross et al., 2010; R. A. Adedoyin et al., 2010). The predictive accuracy of the models was assessed using the coefficient of determination (R2). The relationship between functional and clinical-demographic indicators was assessed using the Pearson or Spearman correlation analysis. RESULTS: The study groups differed significantly in all parameters, except for the proportion of men and the mean VO2peak. Group B patients were 20 years younger than group A patients, had a lower left ventricular ejection fraction (24.06±7.75 and 41.52±10.48 %, respectively; p<0.001), and covered a 130 m shorter distance in the 6MWT. Despite the absence of a significant difference in VO2peak between groups A and B (13.6 and 13.1âml / kg / min, respectively; p=0.6581), 61 % of group B patients and 20% of group A belonged to Weber functional class IV. In group A, the 6MWT distance correlated closely with VO2peak (R=0.78; p<0.01) and weakly with age (R=0.4) and body mass index (R=0.3). In group B, the 6MWT distance correlated only with VO2peak (R=0.77; p<0.01). For group A, the R.M. Ross et al. model demonstrated high accuracy in determining the mean VO2peak value with a 0.06% prediction error normalized to measured VO2peak. For group B, none of the models showed satisfactory predictive accuracy. The Ross and Cahalin models showed the best coefficients of determination for groups A and B: Group A, Ross et al. (R2=0.58) and Cahalin et al. (R2=0.59); Group B, Ross et al. (R2=0.59) and Cahalin et al. (R2=0.6). CONCLUSION: In two groups of patients with a statistically insignificant difference in the mean values of VO2peak, the mean values of 6MWT distance were significantly different, although these indicators correlated closely. The VO2peak prediction models showed satisfactory accuracy for estimation of mean VO2, but poor accuracy for estimation of individual values. A better predictive accuracy is determined by similar clinical and demographic characteristics between the training and testing populations, and likely also by models based on larger, more diversified populations.
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Insuficiência Cardíaca , Função Ventricular Esquerda , Masculino , Humanos , Teste de Caminhada , Volume Sistólico , Consumo de Oxigênio , Teste de Esforço/métodos , Doença Crônica , Insuficiência Cardíaca/diagnósticoRESUMO
Assessing the functional capacity and exercise tolerance is an important and widely used research tool in patients with heart failure. It is used not only in cardiac rehabilitation and physical therapy, but also for inclusion criteria and outcome measures in studies of drug interventions. This document outlines the scope, guidelines for the implementation and interpretation, and limitations of the methods for assessing the functional capacity and exercise tolerance in clinical trials in patients with heart failure.
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Tolerância ao Exercício , Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/tratamento farmacológico , Tolerância ao Exercício/fisiologia , Ensaios Clínicos como Assunto/métodos , Teste de Esforço/métodos , Cardiologia , Reabilitação Cardíaca/métodosRESUMO
This Expert Council focuses on the meta-analysis of studies on the risk of atrial fibrillation (AF) in patients taking omega-3 polyunsaturated fatty acids (PUFA) and of data on the omega-3 PUFA treatment in patients with cardiovascular and kidney diseases.The major statements of the Expert Council: the meta-analysis of AF risk in patients taking omega-3 PUFA showed an increased risk of this arrhythmia. However, it should be taken into account that the risk of complications was low, and there was no significant increase in the risk of AF when omega-3 PUFA was used at a dose of ≤1âg and a standard dose of the only omega-3 PUFA drug registered in the Russian Federation, considering all AF episodes in the ASCEND study.At the present time, according to Russian and international clinical guidelines, the use of omega-3 PUFA can be considered in the following cases: ⢠for patients with chronic heart failure (CHF) with reduced left ventricular ejection fraction as a supplement to the basic therapy (2B class of recommendations according to the 2020 Russian Society of Cardiology guidelines (RSC) and the 2022 AHAâ/âACCâ/âHFSA guidelines); ⢠for patients with hypertriglyceridemia (>1.5 mmol/l) as a part of combination therapy (IIb class of recommendations and B level of evidence according to the 2021 European guidelines on cardiovascular disease prevention, etc.); ⢠for adult patients with stage 3-4 chronic kidney disease (CKD), long-chain omega-3 PUFA 2 g/day is recommended for reducing the level of triglycerides (2C class of recommendations). Data on the use of omega-3 PUFA for other indications are heterogenous, which can be partially explained by using different form and doses of the drugs.
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Fibrilação Atrial , Sistema Cardiovascular , Ácidos Graxos Ômega-3 , Insuficiência Renal Crônica , Adulto , Humanos , Volume Sistólico , Função Ventricular Esquerda , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Federação Russa/epidemiologiaRESUMO
Menopausal symptoms can impair the life of women at the peak of their career and family life. At the present time, the most effective treatment for these manifestations is menopausal hormone therapy (MHT). The presence of cardiovascular and metabolic diseases in itself does not exclude the possibility of prescribing MHT to relieve menopausal symptoms and improve quality of life. However, often an obstacle to the use of this type of hormone therapy is the fear of physicians to do more harm to patients than good. Caution is especially important when it comes to women with concurrent diseases. Moreover, it should be recognized that there is a shortage of high-quality research on the safety of MHT for underlying chronic non-infectious diseases and common comorbidities. The presented consensus analyzed all currently available data from clinical trials of various designs and created a set of criteria for the appropriateness of prescribing MHT to women with concomitant cardiovascular and metabolic diseases. Based on the presented document, physicians of various specialties who advise menopausal women will receive an accessible algorithm that will allow them to avoid potentially dangerous situations and reasonably prescribe MHT in real-life practice.
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Terapia de Reposição de Estrogênios , Qualidade de Vida , Feminino , Humanos , Terapia de Reposição de Estrogênios/efeitos adversos , Consenso , Menopausa , Federação Russa , Terapia de Reposição HormonalRESUMO
Aim To evaluate the incidence of iron deficiency (ID) in men and women with chronic heart failure (CHF) and to compare clinical and functional indexes in patient with and without ID depending on the gender.Material and methods An additional analysis of the study "Prevalence of Iron Deficiency in Patients With Chronic Heart Failure in the Russian Federation (ID-CHF-RF)" was performed. The study included 498 (198 women, 300 men) patients with CHF, in whom, in addition to iron metabolism, the quality of life and exercise tolerance (ET) were studied. 97 % of patients were enrolled during their stay in a hospital. ID was defined in consistency with the European Society of Cardiology (ESC) Guidelines. Also, and additional analysis was performed according to ID criteria validated by the morphological picture of the bone marrow.Results ID was detected in 174 (87.9 %) women and 239 (79.8 %) men (p=0.028) according to the ESC criteria, and in 154 (77.8 %) women and 217 (72.3 %) men (p=0.208) according to the criteria validated by the morphological picture of the bone marrow. Men with ID were older and had more severe CHF. They more frequently had HF functional class (FC) III and IV (63.4 % vs. 43.3 % in men without ID); higher concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and lower ET. HF FC IIIâincreased the probability of ID presence 3.4 times (p=0.02) and the probability of HF FC IVâ13.7 times (p=0.003). This clinical picture was characteristic of men when either method of determining ID was used. In women, ID was not associated with more severe CHF.Conclusion Based on the presented analysis, it is possible to characterize the male and female ID phenotypes. The male ID phenotype is associated with more severe CHF, low ET, and poor quality of life. In females of the study cohort, ID was not associated with either the severity of CHF or with ET.
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Insuficiência Cardíaca , Deficiências de Ferro , Humanos , Feminino , Masculino , Qualidade de Vida , Prevalência , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Doença Crônica , FenótipoRESUMO
Aim To test a hypothesis that increased values of red cell distribution width (RDW) in patients with chronic heart failure (CHF) can be related with low exercise tolerance.Material and methods 102 patients were evaluated who had CHF with mid-range and reduced left ventricular ejection fraction (LV EF) without anemia (72% men, mean age 66±10.2 years). Cardiopulmonary stress test (CPST), echocardiography, 6min walk test (6MWT), blood count, and measurements of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and serum iron were performed.Results The average LV EF was 39±8.7â%; the peak oxygen consumption (VO2peak) was 13.7±4.8âmlâ/kgâ/min; and the median NT-pro-BNP was 595.3âpgâ/ml (Q1-3â1443-2401). RDW variables, including the RDW coefficient of variation (RDW-CV) and RDW standard deviation (RDW-SD), were not significantly related with serum iron or hemoglobin concentrations. A one-factor linear regression analysis showed a significant correlation of VO2peak with RDW-SD (Ñ=0.039). A multivariate linear regression analysis with adjustments for LV EF, hemoglobin concentration, and age did not reveal any significant correlation of VO2peak with RDW variables. The distance covered in the 6MWT was significantly associated with RDW-CV both in the one-factor analysis and with adjustments for LV EF, hemoglobin and serum iron concentrations, and age.Conclusion This study showed that high RDW values in CHF patients without anemia predicted low exercise tolerance regardless of the age, LV systolic function, and hemoglobin and serum iron concentrations. A 16% increase in RDW-CV significantly decreased the likelihood of covering a distance longer than 360 m during 6 min.
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Índices de Eritrócitos , Insuficiência Cardíaca , Idoso , Doença Crônica , Tolerância ao Exercício , Feminino , Hemoglobinas , Humanos , Ferro , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Volume Sistólico , Função Ventricular EsquerdaRESUMO
Aim To evaluate the prevalence of residual symptoms in patients hospitalized for novel coronavirus infection at 8 months after discharge and the severity of such symptoms depending on demographic characteristics, concurrent diseases, and specific features of the acute period of COVID-19.Material and methods This study included the patients who were managed for novel coronavirus infection in a COVID-19 hospital and provided their consent to participate in the study (98 patients). At 8 months after discharge from the hospital, a structured telephone interview was performed.Results Only 40â% of patients treated for COVID-19 did not have any complaints at 8 months after discharge from the hospital. The most frequent complaints in the long term were fatigue (30.5â%), weakness (28.4â%), shortness of breath (23.2â%), arthralgia (22.1â%), myalgia (17.9â%), and anosmia (15.8â%). The background of chronic diseases and obesity, percentage of lung damage according to CT data, and the requirement for oxygen support during the acute period in our sample were not related with the presence of symptoms in the long term. The presence and severity of symptoms during the long term were not determined by the clinical condition, volume of lung damage, or requirement for oxygen support but were related with the gender and severity of inflammation upon admission.Conclusion Independent predictors for persistence of symptoms in the patient sample with severe novel coronavirus infection during the long term included chest and joint pain during the stay in the hospital, female gender, and increased levels of C-reactive protein upon admission.
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COVID-19 , Humanos , Feminino , COVID-19/complicações , COVID-19/epidemiologia , Progressão da Doença , Alta do Paciente , Hospitalização , OxigênioRESUMO
Aim To study the association between vascular wall stiffness and known markers for accumulation of senescent cells in blood, cells, and tissues of old patients.Material and methods This study included male and female patients aged 65 years and older who were referred to an elective surgical intervention, that included a surgical incision in the area of the anterior abdominal wall or large joints and met the inclusion and exclusion criteria. For all patients, traditional cardiovascular (CV) risk factors and arterial wall stiffness (pulse wave velocity, PWV) were evaluated. Also, biomaterials (peripheral blood, skin, subcutaneous adipose tissue) were collected during the surgery and were used for isolation of several cell types and subsequent histological analysis to determine various markers of senescent cells.Results The study included 80 patients aged 65 to 90 years. The correlation analysis identified the most significant indexes that reflected the accumulation of senescent cells at the systemic, tissue, and cellular levels (r>0.3, Ñ<0.05) and showed positive and negative correlations with PWV. The following blood plasma factors were selected as the markers of ageing: insulin-like growth factor 1 (IGF-1), fibroblast growth factor 21 (FGF-21), and vascular endothelium adhesion molecule 1 (VCAM-1). A significant negative correlation between PWV and IGF-1 concentration was found. Among the tissue markers, P16INK, the key marker for tissue accumulation of senescent cells, predictably showed a positive correlation (r=0.394, p<0.05). A medium-strength correlation with parameters of the 96-h increment of mesenchymal stromal cells and fibroblasts and a weak correlation with IL-6 as a SASP (specific senescent-associated secretory phenotype) were noted. Results of the multifactorial linear regression analysis showed that the blood plasma marker, VCAM-1, and the cell marker, 96-h increment of fibroblasts, were associated with PWV regardless of the patient's age.Conclusion Stiffness of great arteries as measured by PWV significantly correlates with a number of plasma, tissue, and cellular markers for accumulation of senescent cells. This fact suggests PWV as a candidate for inclusion in the panel of parameters for evaluation and monitoring of the biological age during the senolytic therapy.
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Análise de Onda de Pulso , Rigidez Vascular , Animais , Biomarcadores , Senescência Celular , Feminino , Fator de Crescimento Insulin-Like I , Masculino , Molécula 1 de Adesão de Célula VascularRESUMO
Aim To evaluate the prevalence of iron deficiency (ID) in Russian patients with heart failure (HF).Material and methods Iron metabolism variables were studied in 498 (198 women, 300 men) patients with HF. Data were evaluated at admission for HF (97â%) or during an outpatient visit (3â%). ID was determined according to the European Society of Cardiology Guidelines.Results 83.1â% of patients had ID; only 43.5â% of patients with ID had anemia. Patients with ID were older: 70.0 [63.0;79.0] vs. 66.0 years [57.0;75.2] (p=0.009). The number of patients with ID increased in parallel with the increase in HF functional class (FC). Among patients with ID, fewer people were past or current alcohol users (p=0.002), and a greater number of patients had atrial fibrillation (60.1 vs. 45.2â%, p=0.016). A multiple logistic regression showed that more severe HF (HF FC) was associated with a higher incidence of ID detection, whereas past alcohol use was associated with less pronounced ID. An increase in N-terminal pro-brain natriuretic peptide (NT-proBNP) by 100âpg/ml was associated with an increased likelihood of ID (odds ratio, 1.006, 95â% confidence interval: 1.002-1.011, p=0.0152).Conclusion The incidence rate of HF patients is high in the Russian Federation (83.1â%). Only 43.5â% of these patients had anemia. The prevalence of ID in the study population increased with increases in HF FC and NT-proBNP.
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Fibrilação Atrial , Insuficiência Cardíaca , Deficiências de Ferro , Idoso , Fibrilação Atrial/complicações , Biomarcadores , Estudos Transversais , Feminino , Insuficiência Cardíaca/complicações , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico , Fragmentos de PeptídeosRESUMO
PURPOSE: Assessment of COVID-19 incidence and hospitalization rate of male patients with prostatic hyperplasia depending on the intake of 5-alpha-reductase inhibitors (5-ARI). MATERIALS AND METHODS: In our study, electronic medical records of 1678 patients with prostatic hyperplasia were analyzed. 1490 men aged 71 (64-76) years were selected for final analysis. Vaccination against COVID-19 was carried out in 730 patients (49%). Treatment with 5-ARI inhibitors was carried out in 269 (18.1%) patients. RESULTS: Among 1490 included patients 790 (53%) had COVID- 19 while 360 (45.7%) of them required hospitalization. During the multivariate analysis, only two factors were associated with the risk of COVID-19 in the cohort studied: vaccination (odds ratio (OR) =0.095; 95% confidence interval (CI) 0.074-0.122), i.e. a 90.5% chance reduction, p<0.001) and the fact of taking 5-ARI (OR=0.235; 95%CI=0.165-0.335; p<0.001), i.e. a 76.5% chance reduction. The duration of 5-ARI therapy was not associated with the incidence of new coronavirus infection. The severe course of COVID-19 which required hospitalization was positively associated with age (p=0.025) and the presence of coronary artery disease (p=0.004); and negatively associated with the frequency of vaccination (p<0.001) and treatment of 5-ARI (3.1% vs. 11.6%, p<0.001). In a multivariate analysis of outpatient patients with prostatic hyperplasia who had COVID-19, 5-ARI intake (OR=0.240; 95% CI 0.122-0.473; p<0.001) and vaccination (OR = 0.570; 95% CI 0.401-0.808; p=0.002). The factors associated with increased chances of hospitalization due to the severe course of COVID-19 were coronary heart disease (+43.8%, p=0.019) and older age (+1.7% by one year, p=0.046). CONCLUSION: Taking 5-ARI, along with vaccination in patients with prostatic hyperplasia is a protective factor for morbidity and the severity of COVID-19.
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COVID-19 , Hiperplasia Prostática , Humanos , Masculino , Hiperplasia Prostática/epidemiologia , Hiperplasia Prostática/terapia , Hiperplasia Prostática/complicações , COVID-19/epidemiologia , COVID-19/terapia , Inibidores de 5-alfa Redutase , Estudos de Coortes , IncidênciaRESUMO
The article presents recent data on possibilities of a broader use of mineralocorticoid receptor antagonists for existing indications and of expanding indications for the use of this pharmaceutical group in the context of the novel coronavirus infection COVID-19. The authors discussed prospects for expanded detection of aldosteronism using a new diagnostic approach, including an additional evaluation of blood pressure response to spironolactone.
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COVID-19 , Hipertensão , Prova Pericial , Humanos , Antagonistas de Receptores de Mineralocorticoides , SARS-CoV-2 , EspironolactonaRESUMO
Aim Activation of the renin-angiotensin-aldosterone system, decreased nitric oxide production, chronic inflammation, and oxidative stress result in subclinical changes in the arterial wall, which favor the development of cardiovascular diseases (CVD). The effect of allelic gene variants that encode the proteins participating in pathogenetic pathways of age-associated diseases with subclinical changes in the arterial wall [increased pulse wave velocity (PWV), increased intima-media thickness, endothelial dysfunction (ED), presence of atherosclerotic plaques (ASP)] are understudied. This study analyzed the relationship between AGT, ACE, NOS3 TNF, MMP9, and CYBA gene polymorphism and the presence of subclinical changes in the arterial wall, including the dependence on risk factors for CVD, in arbitrarily healthy people of various age.Material and methods The relationship of polymorphisms Ñ.521С>Т of AGT gene, Ins>Del of AСE gene, Ñ.894G>T of NOS3 gene, - 238G>A of TNF gene, - 1562С>T of MMP9 gene, and c.214Т>С of CYBA gene with indexes of changes in the arterial wall and risk factors for CVD was studied in 160 arbitrarily healthy people by building models of multiple logistic regression and also by analyzing frequencies of co-emergence of two signs with the Pearson chi-squared test (χ2) and Fisher exact test.Results The DD-genotype of Ins>Del ACE gene polymorphism was correlated with increased PWV (p=0.006; odds ratio (OR) =3.41, 95â% confidence interval (CI): 1.48-8.67) and ED (p=0.014; OR=2.60, 95â% CI: 1.22-5.68). The GG genotype of Ñ.894G>T NOS3 gene polymorphism was correlated with ED (p=0.0087; OR=2.65, 95â% CI: 1.26-5.72); the ТТ-genotype of Ñ.894G>T NOS3 gene polymorphism was correlated with ASP (p=0.033; OR=0.034, 95â% CI: 0.001-0.549).Conclusion Polymorphic variants of AСE and NOS3 genes correlated with ED, increased arterial wall stiffness, and the presence of subclinical changes in the arterial wall.
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Metaloproteinase 9 da Matriz , Análise de Onda de Pulso , Alelos , Espessura Intima-Media Carotídea , Humanos , NADPH Oxidases , Óxido Nítrico Sintase Tipo III/genética , Polimorfismo GenéticoRESUMO
Actuality One of the most widely discussed treatments for patients with COVID-19, especially at the beginning of the epidemy, was the use of the antimalarial drug hydroxychloroquine (HCQ). The first small non-randomized trials showed the ability of HCQ and its combination with azithromycin to accelerate the elimination of the virus and ease the acute phase of the disease. Later, large, randomized trials did not confirm it (RECOVERY, SOLIDARITY). This study is a case-control study in which we compared patients who received and did not receive HCQ.Material and Methods 103 patients (25 in the HCQ treatment group and 78 in the control group) with confirmed COVID-19 (SARS-CoV-2 virus RNA was detected in 26 of 73 in the control group (35.6%) and in 10 of 25 (40%) in the HCQ group) and in the rest - a typical picture of viral pneumonia on multislice computed tomography [MSCT]) were included in the analysis. The severity of lung damage was limited to stages I-II, the CRP level should not exceed 60 mg/dL, and oxygen saturation in the air within 92-98%. We planned to analysis the duration of treatment of patients in the hospital, the days until the normalization of body temperature, the number of points according to the original SHOCS-COVID integral scale, and changes in its components (C-reactive protein (CRP), D-dimer, and the percentage of lung damage according to MSCT).Results Analysis for the whole group revealed a statistically significant increase in the time to normalization of body temperature from 4 to 7 days (by 3 days, p<0.001), and the duration of hospitalization from 9.4 to 11.8 days (by 2.4 days, p=0.002) when using HCQ in comparison with control. Given the incomplete balance of the groups, the main analysis included 46 patients who were matched by propensity score matching. The trend towards similar dynamics continued. HCQ treatment slowed down the time to normalization of body temperature by 1.8 days (p=0.074) and lengthened the hospitalization time by 2.1 days (p=0.042). The decrease in scores on the SHOCS -COVID scale was statistically significant in both groups, and there were no differences between them (delta - 3.00 (2.90) in the HCQ group and - 2.69 (1.55) in control, p=0.718). At the same time, in the control group, the CRP level returned to normal (4.06 mg/dl), and with the use of GC, it decreased but remained above the norm (6.21 mg/dl, p=0.05). Side effects requiring discontinuation of treatment were reported in 3 patients in the HCQ group and none in the control group.Conclusion We have not identified any positive properties of HCQ and its ability to influence the severity of COVID-19. This antimalarial agent slows down the normalization of the body's inflammatory response and lengthens the time spent in the hospital. HCQ should not be used in the treatment of COVID-19.
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Tratamento Farmacológico da COVID-19 , Infecções por Coronavirus , Estudos de Casos e Controles , Humanos , Hidroxicloroquina , SARS-CoV-2 , Resultado do TratamentoRESUMO
Actuality The course of the novel coronavirus disease (COVID-19) is unpredictable. It manifests in some cases as increasing inflammation to even the onset of a cytokine storm and irreversible progression of acute respiratory syndrome, which is associated with the risk of death in patients. Thus, proactive anti-inflammatory therapy remains an open serious question in patients with COVID-19 and pneumonia, who still have signs of inflammation on days 7-9 of the disease: elevated C-reactive protein (CRP)>60 mg/dL and at least two of the four clinical signs: fever >37.5°C; persistent cough; dyspnea (RR >20 brpm) and/or reduced oxygen blood saturation <94% when breathing atmospheric air. We designed the randomized trial: COLchicine versus Ruxolitinib and Secukinumab in Open-label Prospective Randomized Trial in Patients with COVID-19 (COLORIT). We present here data comparing patients who received colchicine with those who did not receive specific anti-inflammatory therapy. Results of the comparison of colchicine, ruxolitinib, and secukinumab will be presented later.Objective Compare efficacy and safety of colchicine compared to the management of patients with COVID-19 without specific anti-inflammatory therapy.Material and Methods Initially, 20 people were expected to be randomized in the control group. However, enrollment to the control group was discontinued subsequently after the inclusion of 5 patients due to the risk of severe deterioration in the absence of anti-inflammatory treatment. Therefore, 17 patients, who had not received anti-inflammatory therapy when treated in the MSU Medical Research and Educational Center before the study, were also included in the control group. The effects were assessed on day 12 after the inclusion or at discharge if it occurred earlier than on day 12. The primary endpoint was the changes in the SHOCS-COVID score, which includes the assessment of the patient's clinical condition, CT score of the lung tissue damage, the severity of systemic inflammation (CRP changes), and the risk of thrombotic complications (D-dimer) [1].Results The median SHOCS score decreased from 8 to 2 (p = 0.017), i.e., from moderate to mild degree, in the colchicine group. The change in the SHOCS-COVID score was minimal and statistically insignificant in the control group. In patients with COVID-19 treated with colchicine, the CRP levels decreased rapidly and normalized (from 99.4 to 4.2 mg/dL, p<0.001). In the control group, the CRP levels decreased moderately and statistically insignificantly and achieved 22.8 mg/dL by the end of the follow-up period, which was still more than four times higher than normal. The most informative criterion for inflammation lymphocyte-to-C-reactive protein ratio (LCR) increased in the colchicine group by 393 versus 54 in the control group (p = 0.003). After treatment, it was 60.8 in the control group, which was less than 100 considered safe in terms of systemic inflammation progression. The difference from 427 in the colchicine group was highly significant (p = 0.003).The marked and rapid decrease in the inflammation factors was accompanied in the colchicine group by the reduced need for oxygen support from 14 (66.7%) to 2 (9.5%). In the control group, the number of patients without anti-inflammatory therapy requiring oxygen support remained unchanged at 50%. There was a trend to shorter hospital stays in the group of specific anti-inflammatory therapy up to 13 days compared to 17.5 days in the control group (p = 0.079). Moreover, two patients died in the control group, and there were no fatal cases in the colchicine group. In the colchicine group, one patient had deep vein thrombosis with D-dimer elevated to 5.99 µg/mL, which resolved before discharge.Conclusions Colchicine 1 mg for 1-3 days followed by 0.5 mg/day for 14 days is effective as a proactive anti-inflammatory therapy in hospitalized patients with COVID-19 and viral pneumonia. The management of such patients without proactive anti-inflammatory therapy is likely to be unreasonable and may worsen the course of COVID-19. However, the findings should be treated with caution, given the small size of the trial.
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COVID-19 , Colchicina/uso terapêutico , Infecções por Coronavirus , SARS-CoV-2 , Anti-Inflamatórios/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Humanos , Estudos Prospectivos , Resultado do TratamentoRESUMO
The document focuses on key issues of diuretic therapy in CHF from the standpoint of current views on the pathogenesis of edema syndrome, its diagnosis, and characteristics of using diuretics in various clinical situations.
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Diuréticos , Insuficiência Cardíaca , Doença Crônica , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Federação RussaRESUMO
Introduction Coronavirus pneumonia not only severely affects the lung tissue but is also associated with systemic autoimmune inflammation, rapid overactivation of cytokines and chemokines known as "cytokine storm", and a high risk of thrombosis and thromboembolism. Since there is no specific therapy for this new coronavirus infection (COVID-19), searching for an effective and safe anti-inflammatory therapy is critical.Materials and methods This study evaluated efficacy and safety of pulse therapy with high doses of glucocorticosteroids (GCS), methylprednisolone 1,000 mg for 3 days plus dexamethasone 8 mg for another 3-5 days, in 17 patients with severe coronavirus pneumonia as a part of retrospective comparative analysis (17 patients in control group). The study primary endpoint was the aggregate dynamics of patients' condition as evaluated by an original CCS-COVID scale, which included, in addition to the clinical status, assessments of changes in the inflammation marker, C-reactive protein (CRP); the thrombus formation marker, D-dimer; and the extent of lung injury evaluated by computed tomography (CT). Patients had signs of lung injury (53.2â% and 25.6â%), increases in CRP 27 and 19 times, and a more than doubled level of D-dimer (to 1.41 µg/ml and 1.15 µg/ml) in the active therapy and the control groups, respectively. The GCS treatment group had a more severe condition at baseline.Results The GCS pulse therapy proved effective and significantly decreased the CCS-COVID scores. Median score difference was 5.00 compared to the control group (Ñ=0.011). Shortness of breath considerably decreased; oxygen saturation increased, and the NEWS-2 clinical status scale scores decreased. In the GCS group, concentration of CRP significantly decreased from 134âmg/dl to 41.8âmg/dl (Ñ=0.009) but at the same time, D-dimer level significantly increased from 1.41 µg/ml to 1.98 µg/ml (Ñ=0.044). In the control group, the changes were nonsignificant. The dynamics of lung injury by CT was better in the treatment group but the difference did not reach a statistical significance (Ñ=0.062). Following the GCS treatment, neutrophilia increased (Ñ=0.0001) with persisting lymphopenia, and the neutrophil/lymphocyte (N/L) ratio, a marker of chronic inflammation, increased 2.5 times (Ñ=0.006). The changes in the N/L ratio and D-dimer were found to correlate in the GCS pulse therapy group (r =0.49, p=0.04), which underlined the relationship of chronic autoimmune inflammation with thrombus formation in COVID-19. No significant changes were observed in the control group. In result, four patients developed venous thromboembolic complications (two of them had pulmonary artery thromboembolism) after the GCS pulse therapy despite the concomitant antiplatelet treatment at therapeutic doses. Recovery was slower in the hormone treatment group (median stay in the hospital was 26 days vs 18 days in the control group, Ñ=0.001).Conclusion Pulse therapy with high doses of GCS exerted a rapid anti-inflammatory effect but at the same time, increased the N/L ratio and the D-dimer level, which increased the risk of thromboembolism.
Assuntos
Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Esteroides/efeitos adversos , Trombose Venosa , COVID-19 , Infecções por Coronavirus/tratamento farmacológico , Humanos , Inflamação , Pneumonia Viral/tratamento farmacológico , Estudos Retrospectivos , SARS-CoV-2 , Trombose Venosa/induzido quimicamente , Tratamento Farmacológico da COVID-19RESUMO
The article is devoted to the treatment of the new coronavirus infection (COVID-19) in the advanced stages of the disease. The types of response of the immune system to the viral load of SARS-CoV-2 with the start of the inflammation process are considered. The situation is analyzed in detail in which the growing autoimmune inflammation (up to the development of a "cytokine storm") affects not only the pulmonary parenchyma, but also the endothelium of the small vessels of the lungs. Simultaneous damage to the alveoli and microthrombosis of the pulmonary vessels are accompanied by a progressive impairment of gas exchange, the development of acute respiratory distress syndrome, the treatment of which, even with the use of invasive ventilation, is ineffective and does not really change the prognosis of patients with COVID-19. In order to interrupt the pathological process at the earliest stages of the disease, the necessity of proactive anti-inflammatory therapy in combination with active anticoagulation treatment is substantiated. The results of the first randomized studies on the use of inhibitors of pro-inflammatory cytokines and chemokines (interleukin-6 (tocilizumab), interleukin-17 (secukinumab), Janus kinase blockers, through which the signal is transmitted to cells (ruxolitinib)), which have potential in the early treatment of COVID- 19. The use of a well-known anti-inflammatory drug colchicine (which is used for gout treatment) in patients with COVID-19 is considered. The design of the original COLORIT comparative study on the use of colchicine, ruxolitinib and secukinumab in the treatment of COVID-19 is presented. Clinical series presented, illustrated early anti-inflammatory therapy together with anticoagulants in patients with COVID-19 and the dangers associated with refusing to initiate such therapy on time.
Assuntos
Colchicina , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados , Anticoagulantes/uso terapêutico , Betacoronavirus , COVID-19 , Colchicina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Humanos , Nitrilas , Estudos Prospectivos , Pirazóis , Pirimidinas , SARS-CoV-2 , Tratamento Farmacológico da COVID-19RESUMO
The article focuses on effective treatment of the novel coronavirus infection (COVID-19) at early stages and substantiates the requirement for antiviral therapy and for decreasing the viral load to prevent the infection progression. The absence of a specific antiviral therapy for the SARS-CoV-2 virus is stated. The authors analyzed results of early randomized studies using lopinavir/ritonavir, remdesivir, and favipiravir in COVID-19 and their potential for the treatment of novel coronavirus infection. Among the drugs blocking the virus entry into cells, the greatest attention was paid to the antimalaria drugs, chloroquine and hydroxychloroquine. The article addresses in detail ineffectiveness and potential danger of hydroxychloroquine, which demonstrated neither a decrease in the time of clinical recovery nor any improvement of prognosis for patients with COVID-19. The major objective was substantiating a possible use of bromhexine, a mucolytic and anticough drug, which can inhibit transmembrane serin protease 2 required for entry of the SARS-CoV-2 virus into cells. Spironolactone may have a similar feature. Due to its antiandrogenic effects, spironolactone can inhibit X-chromosome-related synthesis of ACE-2 receptors and activation of transmembrane serin protease 2. In addition to slowing the virus entry into cells, spironolactone decreases severity of fibrosis in different organs, including the lungs. The major part of the article addresses clinical examples of managing patients with COVID-19 at the University Clinic of the Medical Research and Educational Centre of the M. V. Lomonosov Moscow State University, including successful treatment with schemes containing bromhexine and spironolactone. In conclusion, the authors described the design of a randomized, prospective BISCUIT study performed at the University Clinic of the M. V. Lomonosov Moscow State University with an objective of evaluating the efficacy of this scheme.
Assuntos
Bromoexina , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Espironolactona , Betacoronavirus , Bromoexina/uso terapêutico , COVID-19 , Infecções por Coronavirus/tratamento farmacológico , Hospitalização , Humanos , Moscou , Pneumonia Viral/tratamento farmacológico , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2 , Espironolactona/uso terapêutico , Tratamento Farmacológico da COVID-19RESUMO
Introduction The aim of this study was to assess the efficacy and safety of a combination of bromhexine at a dose of 8 mg 4 times a day and spironolactone 50 mg per day in patients with mild and moderate COVID 19.Material and methods It was an open, prospective comparative non-randomized study. 103 patients were included (33 in the bromhexine and spironolactone group and 70 in the control group). All patients had a confirmed 2019 novel coronavirus infection (COVID 19) based on a positive polymerase chain reaction (PCR) for SARS-CoV-2 virus RNA and/or a typical pattern of viral pneumonia on multispiral computed tomography. The severity of lung damage was limited to stage I-II, the level of CRP should not exceed 60 mg / dL and SO2 in the air within 92-98%. The duration of treatment is 10 days.Results The decrease in scores on the SHOKS-COVID scale, which, in addition to assessing the clinical status, the dynamics of CRP (a marker of inflammation), D-dimer (a marker of thrombus formation), and the degree of lung damage on CT (primary endpoint) was statistically significant in both groups and differences between them was not identified. Analysis for the group as a whole revealed a statistically significant reduction in hospitalization time from 10.4 to 9.0 days (by 1.5 days, p=0.033) and fever time from 6.5 to 3.9 days (by 2.5 days, p<0.001). Given the incomplete balance of the groups, the main analysis included 66 patients who were match with using propensity score matching. In matched patients, temperature normalization in the bromhexine/spironolactone group occurred 2 days faster than in the control group (p=0.008). Virus elimination by the 10th day was recorded in all patients in the bromhexine/spironolactone group; the control group viremia continued in 23.3% (p=0.077). The number of patients who had a positive PCR to the SARS-CoV-2 virus on the 10th day of hospitalization or longer (≥10 days) hospitalization in the control group was 20/21 (95.2%), and in the group with bromhexine /spironolactone -14/24 (58.3%), p=0.012. The odds ratio of having a positive PCR or more than ten days of hospitalization was 0.07 (95% CI: 0.008 - 0.61, p=0.0161) with bromhexine and spironolactone versus controls. No side effects were reported in the study group.Conclusion The combination of bromhexine with spironolactone appeared effective in treating a new coronavirus infection by achieving a faster normalization of the clinical condition, lowering the temperature one and a half times faster, and reducing explanatory combine endpoint the viral load or long duration of hospitalization (≥ 10 days).
Assuntos
Bromoexina , COVID-19 , Infecções por Coronavirus , Hospitalização , Humanos , Estudos Prospectivos , SARS-CoV-2 , Espironolactona , Resultado do TratamentoRESUMO
The article discusses pathogenesis and treatment of COVID-19. The authors presented state-of-the-art insight into hemostatic disorders in patients with COVID-19 and clinical recommendations on prevention of thrombosis and thromboembolism in patients infected with SARS-CoV-2. The article discussed in detail a new hypothesis proposed by Chinese physicians about a new component in the pathogenesis of COVID-19, namely, about the effect of SARS-CoV-2 virus on the hemoglobin beta-chain and the formation of a complex with porphyrin, which results in displacement of the iron ion. Thus, hemoglobin loses the capability for transporting oxygen, which aggravates hypoxia and worsens the prognosis. The article stated rules of hemotransfusion safety in the conditions of COVID-19 pandemic.